Largest exhibition of Guido Reni—
Frankfurt’s Städel Museum will present around 130 of his paintings, drawings and etchings
“ Bologna’s supreme Baroque artist, Guido Reni (1575-1642), was known in his lifetime as “the divine”, referring to his celestial talents and subject matter.
Frankfurt’s Städel Museum hopes to bring the lustre back to Reni’s star this month by presenting around 130 of his paintings, drawings and etchings in Guido Reni: The Divine. The exhibition, which also includes some 35 comparative works of art and other objects, comprises the largest number of autograph works by the artist brought together in one place, says the exhibition curator Bastian Eclercy, who is the Städel’s expert in Italian Renaissance and Baroque painting.
Divine”—an epithet that Reni’s contemporaries also used to remark on his diva-like manner—is a concise word for summing up the artist’s oeuvre, which was concerned almost exclusively with Christian and mythological imagery. Basking in the patronage of Rome’s Borghese family, he was able to break away from early influences, such as the Carracci clan of his native Bologna and Caravaggio himself, and arrive at an elegant, harmonious synthesis of earlier styles.
The show, which begins with a biographical overview, establishes Reni as a contradictory character who was deeply religious, Eclercy says, as well as a high-earning compulsive gambler who “lost in the evening what he earned in the morning”. Reni’s Madonnas—which launched centuries of imitations and, his harshest critics might suggest, paved the way for religious kitsch—are represented here with pathos-filled iterations, including Immaculate Conception (1627) on loan from New York’s Metropolitan Museum of Art.
Eclercy says Reni showed no outward signs of a romantic life. Reni has the apple-seeking huntress bending away from her gorgeous would-be suitor, as he makes his own star turn. The life-size work, which has recently undergone conservation treatment, is on loan from Madrid’s Museo Nacional del Prado, whose own Reni show next spring will share around 30 core works with the Städel’s (28 March-9 July 2023).
Eclercy has incorporated new findings and theories in the show, including the argument that David with the Head of Goliath, a recently cleaned painting on loan from France’s Musée des Beaux-Arts in Orléans, should be regarded as another autograph version, and possibly earlier than the version at the Musée du Louvre, long thought to have come first. Meanwhile, a remarkable loan from the Louvre serves as the show’s centrepiece: in the Allegory of the Union of Drawing and Painting (around 1625), the handsome youth representing drawing is gazing into the eyes of the beautifully adorned maiden who stands for painting. Reni’s depiction of heterosexual love is a match made in heaven.”
The Art Journal
IP Addresses—The Next Big Privacy Concern
“With the invention of the internet years ago, new ways to market to consumers quickly arose—and companies seized the opportunity. Marketers used different means to track interactions to determine when and how to reach consumers with the right messaging, which meant they were no longer throwing darts in the dark. But with the rise of privacy concerns, internet giants and legislatures have started to put an end to the gathering of individuals’ internet habits.
As a result, the collection (and use) of third-party cookies is coming to an end, and another internet tool will likely follow—the IP address. IP addresses are used to determine approximate user location such as city and zip code, identify your internet service provider’s name and log internet activity within a session. Working much like a social security number, an IP address is assigned to an individual computer each time it accesses the internet, identifying the computer and allowing for the interaction of the servers and computers to communicate across platforms. An IP address doesn’t reveal personal information per se; however, it does reveal pieces of personal identifiable information (PII) that anyone with a little know-how can access. IP addresses are necessary as the function of the internet is predicated on this technology, but any information made public becomes an opportunity for misuse by cyber criminals.
Internet giants like Apple and Google have started to limit the usage of IP addresses, with technologies such as Apple’s Intelligent Tracking Prevention (ITP), which blocks cross-site tracking and allows users to use fake IP addresses. IP address cloaking is also becoming popular with services built to allow users to hide their IP addresses by connecting them to a shared server or a virtual private network (VPN).
Likewise, Google, which more than half of the world’s population uses, will ban third-party cookie use sometime in 2024 as it continues to delay the inevitable. While that has changed most data collection practices, it has not yet affected IP addresses. Advertisers are using IP addresses in a similar way to how cookies are tracked—once a user clicks on a website or an ad, the advertiser can grab a snapshot of the IP address. The IP address allows advertisers to direct ads to users in specific geographic locations and piece together a profile of your interests and online behaviors to deliver targeted ads. They can also be used to block users from viewing content in specific areas or from chat rooms. Law enforcement uses IP addresses to help build cases by finding clues or tracking down a name or address and accessing emails with a court order. As laws are updated, and users become more aware of the implications of IP addresses, finding an alternative is a more realistic next step.
Businesses continue to seek opportunities to track individuals, engagement and consent, all while staying compliant under global data and privacy regulations such as GDPR, CCPA, APEC and the laws that are set to follow. And companies continue to feel the pressure to gather that information to remain competitive. As a result, companies building solutions around IP addresses ultimately will find themselves in the same poor light as the third-party world already has.
A solution that many marketers should gravitate toward is the use of first-party compliant data capture, which would allow companies to gather and own their own information to build profiles for marketing from their own digital channels. The user consents to the capture of their information to create the best customer experience on that website, trading information for a one-to-one personalized experience and messaging tailored to their needs. The user benefits from this type of data collection because they have consented to it, and there is no privacy concern. Ultimately, first-party data is the only true path forward in today’s marketplace, as many of the other solutions being presented today look and smell a lot like the old ways that have now been blocked or heavily restricted.
Brands that adopt a “head in the sand” model, or continue to operate as such, will find themselves at a competitive disadvantage in the marketplace. There is no easy solution to replace many of the third-party practices, but the foundation for finding your way through these murky waters starts with compliant first-party data and builds from there.”
Healthy Brain Needs Proper Diet and Exercise
“Healthy brain aging is a concern for all of us. It’s normal to struggle with small things such as recalling names—and we all experience some slowing of the thought processes with advanced age—but everyone hopes to avoid serious cognitive impairment.
Some cognitive difficulties, such as Alzheimer’s disease, have underlying pathological causes that we are still working to understand. However, we know that brains can also lose function simply through poor physical, mental and social health. Many of the causes of cognitive decline are preventable.
Just as we create exercise regimens for the body, we should create a routine for brain health.
As a general rule, what is good for heart health is good for brain health. Getting regular exercise, eating well and maintaining a healthy weight all promote a healthy brain.
People of all ages, particularly seniors, benefit from leaving the house, engaging in learning activities and having an active social life. It is important to commit to a schedule that encourages all of these healthy brain aging activities.
In any weather conditions there is an opportunity to get physical exercise through gardening and walking. Many community organizations offer some classes in dance, photography, art, music and other hobbies.
Fresh fruits and vegetables contain compounds called plant polyphenols. These compounds, which help plants fight off disease, have been observed in animal models to extend lifespan by promoting general cellular health. Blackberries, raspberries, blueberries and red wine are all good sources of polyphenols.
Anyone interested in healthy brain aging also can practice “neurobics.” These “aerobics for the brain” are activities that can be thrown into the daily schedule on a whim. Examples include taking a different route home, shopping at a different grocery store, or purposely driving or walking through an unfamiliar neighborhood. These simple activities activate the problem-solving areas of the brain as the person navigates unfamiliar territory.
Social engagement is key for seniors, who might find their social circle shrinking as friends and relatives move, develop serious illness or die.
Senior centers offer great resources for social activities. Something as simple as gathering with others for a regular card game can help keep the cognitive functions of the brain sharp.
Through socialization, hobbies, lifelong learning, healthy eating, physical activity and challenging their brain on a daily basis, most people have the capacity to achieve healthy brain aging.
There are patients who reverse mild cognitive impairment simply by adopting a healthier lifestyle—so it’s never too late to encourage healthy brain aging.”
The dream of electric-powered flying cars & the reality check
“Kittyhawk, a secretive air-taxi startup backed by Google co-founder Larry Page, winds down. It underscores how difficult it will be to get electric-powered flying cars and planes.
The dream of flying cars zipping around in the air has suffered a major reality check.
Recently, the secretive air-taxi start-up Kittyhawk, run by Google veteran Sebastian Thrun, announced on Twitter that it was going to “wind down.” It was one of a handful of companies working to bring a “Jetsons” like reality to the world, where electric-powered cars, planes and helicopters become commonplace and offer clean-burning modes of transportation to a world of clogged and polluted streets.
After launching over a decade ago, the flying car company backed by Google co-founder Larry Page garnered fanfare typical of moonshot ideas championed by Silicon Valley titans — and was largely seen as one of the most likely to make a breakthrough.
“Silicon Valley constantly putting out these ideas for how we solve the problems of transportation and urban life with new technologies,” said Paris Marx, a technology critic and host of the podcast Tech Won’t Save Us. “That has been an utter failure.”
Kittyhawk, like many of its competitors, made bold promises on its website of building a fleet of air-taxis that are “ultra-quiet and battery-efficient,” and could fly hundreds of miles on a single charge while being nearly silent within 30 seconds of taking off. “If anyone can do this,” the company’s site said, “we can.”
Representatives from Kittyhawk did not return a request for comment.
The start-up’s collapse highlights the challenges in mastering flying transportation, experts said. Battery technology needs to advance far past its current state. Getting regulatory approval for flying cars will be difficult. And the infrastructure to support a world of flying cars and vehicles is a vastly complex challenge.
Even Elon Musk has said: everything works in PowerPoint,” said Peter Rez, an emeritus physics professor from Arizona State University, but “things are never going to work as advertised.”
Investors have poured billions into start-ups looking to change how people get around. In 2021, air mobility start-ups raked in record $6.9 billion in investment, a large chunk of which went to electric vehicles that take off and land, known as eVTOLs. The pace of funding slowed in the first half of 2022, McKinsey analysts noted.
Despite the cash, flying cars have suffered a string of major setbacks, according to media reports. A Forbes investigation of Kittyhawk in 2019 alleged the company was plagued with battery and safety issues.
Rez said lithium-ion battery problems will be a constant challenge for the industry. They output energy at a 50 times less efficient rate than their gasoline counterparts, requiring more to be on board, adding to cost and flying car and plane weight.
Companies are clinging to hope that battery technology will advance rapidly, he said, though it’s not clear when that will happen.
Lithium ion batteries have been known to catch fire, and scientists understand advancing the highly flammable part of the battery, called an electrolyte, is necessary but proving scientifically difficult.
Aviation agencies, Rez added, require commercial planes to have enough reserve power to fly for at least 30 to 45 minutes past their destination, another challenge.
Marx noted that Silicon Valley moonshots are unlikely to succeed alone. To achieve widespread adoption of flying taxis and planes, it would require more airports, federal coordination and large-scale infrastructure planning.
“Ultimately, these are political problems that require political solutions,” Marx said. “Technologies alone cannot solve that.”
The Washington Post
Silicon Valley’s latest wild bet:
living much longer & making people younger
Anti aging companies are pursuing biological reprogramming technology, a way to rejuvenate cells in the lab that some scientists think could be extended to revitalize entire animal bodies, ultimately prolonging human life.
“It’s been said that young people dream of being rich, and rich people dream of being young.”
“In October 2020, a large group of scientists made their way to Yuri Milner’s super-mansion in the Los Altos Hills above Palo Alto. They were tested for covid-19 and wore masks as they assembled in a theater on the property for a two-day scientific conference. Others joined by teleconference. The topic: how biotechnology might be used to make people younger.
Milner is a Russian-born billionaire who made a fortune on Facebook and previously started the glitzy black-tie Breakthrough Prizes, $3 million awards given each year to outstanding physicists, biologists, and mathematicians. But Milner’s enthusiasm for science was taking a provocative and specific new direction. As the scientific sessions progressed, experts took the stage to describe radical attempts at “rejuvenating” animals.
That meeting has now led to the formation of an ambitious new anti-aging company called Altos Labs, according to people familiar with the plans. Altos is pursuing biological reprogramming technology, a way to rejuvenate cells in the lab that some scientists think could be extended to revitalize entire animal bodies, ultimately prolonging human life.
The new company, incorporated in the US and in the UK earlier in 2021, has establish several institutes in places including the Bay Area, San Diego, Cambridge, UK and Japan, and is recruiting a large cadre of university scientists with lavish salaries and the promise that they can pursue unfettered blue-sky research on how cells age and how to reverse that process.
Some people briefed by the company have been told that its investors include Jeff Bezos, and Milner and his wife Julia have invested in Altos through a foundation.
Altos is certain to draw comparisons to Calico Labs, a longevity company announced in 2013 by Google co-founder, Larry Page.
Calico also hired elite scientific figures and gave them generous budgets, although it’s been questioned whether the Google spinout has made much progress. Calico has also started a lab whose focus is reprogramming; it published its first preprint on the topic last year.
Among the scientists said were joining Altos are Juan Carlos Izpisúa Belmonte, a Spanish biologist at the Salk Institute, in La Jolla, California, who has won notoriety for research mixing human and monkeys embryos and who has predicted that human lifespans could be increased by 50 years. Salk declined to comment.
Also joining is Steve Horvath, a UCLA professor and developer of a biological clock that can accurately measure human aging. Shinya Yamanaka, who shared a 2012 Nobel Prize for the discovery of reprogramming, will be a senior scientist and will chair the company’s scientific advisory board.
Yamanaka’s breakthrough discovery was that with the addition of just four proteins, now known as Yamanaka factors, cells can be instructed to revert to a primitive state with the properties of embryonic stem cells. By 2016, Izpisúa Belmonte’s lab had applied these factors to entire living mice, achieving signs of age reversal and leading him to term reprogramming a potential “elixir of life.”
The results of such mouse experiments, while tantalizing, were also frightening. Depending on how much reprogramming occurred, some mice developed ugly embryonic tumors called teratomas, even as others showed signs their tissues had become younger.
Although there are many hurdles to overcome, there is huge potential,” Yamanaka said in an email, in which he confirmed his role in Altos.
It’s been said that young people dream of being rich, and rich people dream of being young. That paradox is one that people like Milner, age 59, and Bezos, who is 57 years old, may feel acutely.
Bezos Expeditions, the investment office of Amazon’s founder, did not reply to an email seeking comment.
People familiar with the formation of Altos say that initially Milner’s interest in reprogramming was philanthropic. After the meeting at his home, a non-profit called the Milky Way Research Foundation sponsored by Milner awarded three-year grants, of $1 million a year, to several longevity researchers. The proposals were considered by an advisory board including Yamanaka and Jennifer Doudna, who shared a Breakthrough Prize in 2015 and later a Nobel in 2020 for her co-discovery of CRISPR genome editing.
Sometime during 2021, however, a new plan emerged to make the research move even faster by turning the idea into a well-funded company that is now Altos. That effort took shape under the direction of Richard Klausner, the one-time chief of the National Cancer Institute and now an entrepreneur. Klausner, who previously helped start companies like Juno Therapeutics and cancer-test company Grail, is known for organizing large, and lucrative, financial bets on new biotechnologies.
According to an incorporation filing in the UK for Altos Labs, Klausner is CEO of the new company. Klausner did not respond to attempts to contact him by email and phone. Like Milner, he also lives in Los Altos Hills.
A number of startups are pursuing reprogramming technology, including Life Biosciences, Turn Biotechnologies, AgeX Therapeutics, and Shift Bioscience in the UK, although these efforts have not yet led to any treatments tested on people in clinical trials.
“There are hundreds of millions of dollars being raised by investors to invest in reprogramming, specifically aimed at rejuvenating parts or all of the human body,” says David Sinclair, a researcher at Harvard University who reported restoring sight to mice using the technique.
Sinclair describes the field as “nascent” but thinks it has unique promise. “What else can you do that can reverse the age of the body?” he says. “In my lab we are ticking off the major organs and tissues, for instance skin, muscle and brain —to see which we can rejuvenate.” Sinclair says he is not involved in Altos but he did speak at the 2020 meeting and applied for an award from Milky Way.
A science business
Altos hasn’t made an official announcement yet, but it was incorporated in Delaware this year and a securities disclosure filed in California in June indicates the company has raised at least $270 million, according to Will Gornall, a business school professor at the University of British Columbia who reviewed the document. In addition to Bezos and Milner, the company may have additional wealthy tech figures and venture capitalists as investors.
Other hires made by Altos include Peter Walter, whose laboratory at the University of California, San Francisco, is behind a molecule that shows remarkable effects on memory. Also joining is Wolf Reik, a reprogramming specialist who recently resigned as the director of the Babraham Institute in the UK after the center said he was taking a job “with another research organization” now believed to be Altos. Walter and Reik declined to comment.
At least initially, Altos will be funding researchers with no immediate expectation for products or revenues. According to one person briefed by Klausner and Milner, the initial output of the company will be “great science.”
Altos is luring university professors by offering sports-star salaries of $1 million a year or more, plus equity, as well as freedom from the hassle of applying for grants. One researcher who confirmed accepting a job offer from Altos, Manuel Serrano of the Institute for Research in Biomedicine, in Barcelona, Spain, said the company would pay him five to 10 times what he earns now.
“The philosophy of Altos Labs is to do curiosity-driven research. This is what I know how to do and love to do,” says Serrano, who plans to move to Cambridge, UK to join an Altos facility there. “In this case, through a private company, we have the freedom to be bold and explore. In this way it will rejuvenate me.”
Any treatment for a major disease of aging could be worth billions, but Altos isn’t counting on making money at first. “The aim is to understand rejuvenation,” says Serrano. “I would say the idea of having revenue in the future is there, but it’s not the immediate goal.”
In 2013, Serrano was among the first scientists to genetically engineer mice to produce Yamanaka factors. They all developed tumors as their cells reverted to an embryonic stage. Still, the work hinted that time could be reversed inside a living animal. “You introduce the factors and they do the magic. It’s very simple experimentally, even if it is not understood,” says Serrano.
The major question now is how to tailor reprogramming to see if it can safely rejuvenate animals without killing them, and whether the process can be carried out using ordinary drugs, rather than via genetic engineering. “To me the Yamanaka factors are not realistic for use in the clinic,” Serrano says. “They involve the introduction of genes, some of which are oncogenic. This is hard to pass through the filter of regulatory agencies.”
Some experts say investment in anti-aging techniques is something government funding agencies are not able to do quickly enough. “If you see something in the distance that looks like a giant pile of gold, then you should run quickly,” says Martin Borch Jensen, chief scientific officer of Gordian Biotechnology. To speed research, Jensen says last year he was giving out $20 million worth of rapid turn-around Impetus grants using funds from donors.
“There’s a big bet now,” Jensen says. “It’s ‘Let’s see if reprogramming works. Let’s see if molecular clocks can be biomarkers.’ If it does work, it’s going to have a huge impact.
Some researchers question whether reprogramming is a technology that can really benefit from hundreds of millions in commercial investment. Alejandro Ocampo, who used to work in Izpisúa Belmonte’s Salk lab, and is now a professor at the University of Lausanne in Switzerland, is skeptical that reprogramming technology is ready to turn into medicine any time soon.
“I think the concept is strong, but there is a lot of hype. It’s far away from translation,” he says. “It’s risky and it’s a long way from a human therapy.” One problem is that reprogramming doesn’t just make cells act younger but also changes their identity—for instance, turning a skin cell into a stem cell. That is what makes the technology too dangerous to try on people yet.
Ocampo also worries that there is too much money, and too many companies, trying to get into the research area. “I think it’s moving too fast. I don’t know if we should have five to eight reprogramming companies —it looks too quick,” he says. “How many papers have there even been in in vivo reprogramming? It’s the same as the number of companies.”
On the other hand, the technique has an indisputable, repeatable, effect in laboratory experiments when applied to individual cells. “You can take a cell from an 80-year old and, in vitro, reverse the age by 40 years. There is no other technology that can do that,” says Ocampo.
What’s more, reprogramming is also recognized as a key process that occurs naturally when a fertilized egg turns into an embryo and, nine months later, leads to a fresh-faced baby. Somehow, the DNA of the parents is scrubbed, renewed, and restarted. After trillions of baby animals have been born over a billion years, Ocampo thinks it’s safe to say that “reprogramming is one of the experiments that has been reproduced the most.”
Altos will also be working with a related technology for measuring the relative age of a cell, or a person. That biological-clock technique, pioneered by Horvath, involved measuring the “epigenetic” marks on genes. These molecular features turn genes on and off, but their pattern becomes disorganized as people age. Such a biomarker of aging would be an important way to measure the effect of any longevity or age-reversal drug that is developed. It’s difficult to run a medical study that demonstrates life extension, since it would take too long, but a biomarker could be employed instead.
There is also a strong scientific connection between aging clocks and reprogramming, since reprogramming appears to work by remodeling the epigenetic marks in a cell’s genome to an immature or naive state. That means Altos will be working at the leading edge of both causing and measuring rejuvenation.
Young and rich
Bezos is said to have a fairly long-standing interest in longevity research, and he previously invested in an anti-aging company called Unity Biotechnology. Rumors of the billionaire making a seismic-sized splash into the field have swirled for months.
While Technology Review could not confirm his stake in Altos, what’s sure is that getting older is on his mind. Bezos included a quote ruminating on death and decay that he’d found in a book by the biologist Richard Dawkins: “Staving off death is a thing that you have to work at…If living things don’t actively work to prevent it, they would eventually merge with their surroundings and cease to exist as autonomous beings. That is what happens when they die.”
Bezos meant that nations, companies, and individuals have to fight to remain distinct, original and unique. Rewinding the clock to your younger days could be one way to do that.” MIT Technology Review
Intestinal viruses were found to be infectious for up to three days by attaching to microplastics, research shows
“Dangerous viruses can remain infectious for up to three days in fresh water by hitchhiking on plastic, researchers have found.
Enteric viruses that cause diarrhoea and stomach upsets, such as rotavirus, were found to survive in water by attaching to microplastics, tiny particles less than 5mm long. They remain infectious, University of Stirling researchers found, posing a potential health risk.
Prof Richard Quilliam, lead researcher on the project at Stirling University, said: “We found that viruses can attach to microplastics and that allows them to survive in the water for three days, possibly longer.”
While previous research had been carried out in sterile settings, this is the first research into how viruses behave in the environment, Quilliam said. However, he used standard laboratory methods to determine whether viruses found on microplastics in water were infectious.
“We weren’t sure how well viruses could survive by ‘hitchhiking’ on plastic in the environment, but they do survive and they do remain infectious,” he said.
The findings, part of a £1.85m project funded by the Natural Environment Research Council looking at how plastics transport bacteria and viruses, concluded that microplastics enabled pathogen transfer in the environment. The paper is published in the journal Environmental Pollution.
“Being infectious in the environment for three days, that’s long enough to get from the wastewater treatment works to the public beach,” Quilliam said.
Wastewater treatment plants were unable to capture microplastics, he said. “Even if a wastewater treatment plant is doing everything it can to clean sewage waste, the water discharged still has microplastics in it, which are then transported down the river, into the estuary and wind up on the beach.”
These plastic particles are so tiny that they could be swallowed by swimmers. “Sometimes they wash up on the beach as lentil-sized, brightly coloured pellets called nurdles that children might pick up and put in their mouths. It doesn’t take many virus particles to make you sick,” Quilliam said.
While the impact of microplastics on human health remains uncertain, “if those bits of microplastics are colonised by human pathogens, then that could well be a significant health risk,” said Quilliam.
The researchers tested two types of viruses – those with an envelope around them, “a kind of lipid coat”, such as the flu virus, and those without – enteric viruses such as rotavirus and norovirus. They found that in those with a coating, the envelope quickly dissolved and the virus died, whereas those without an envelope successfully bound to the microplastics and survived.
“Viruses can also bind to natural surfaces in the environment,” said Quilliam, “but plastic pollution lasts a lot longer than those materials.”
The researchers tested the viruses for three days, but aim to study how long they might remain infectious in future research.
Another study by Quilliam’s team last month discovered levels of faecal bacteria on wet wipes and cotton buds washed up on beaches posed a health risk. They first found sewage bacteria “hitchhiking” on plastic pellets on Scottish beaches in 2019.” Our Oceans
CRISPR, 10 Years On:
Learning to Rewrite the Code of Life
The gene-editing technology has led to innovations in medicine, evolution and agriculture — and raised profound ethical questions about altering human DNA.
“Ten years ago, Jennifer Doudna and her colleagues published the results of a test-tube experiment on bacterial genes. When the study came out in the journal Science on June 28, 2012, it did not make headline news. In fact, over the next few weeks, it did not make any news at all.
Looking back, Dr. Doudna wondered if the oversight had something to do with the wonky title she and her colleagues had chosen for the study: “A Programmable Dual RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity.”
“I suppose if I were writing the paper today, I would have chosen a different title,” Dr. Doudna, a biochemist at the University of California, Berkeley, said in an interview.
Far from an esoteric finding, the discovery pointed to a new method for editing DNA, one that might even make it possible to change human genes.
“I remember thinking very clearly, when we publish this paper, it’s like firing the starting gun at a race,” she said.
In just a decade, CRISPR has become one of the most celebrated inventions in modern biology. It is swiftly changing how medical researchers study diseases: Cancer biologists are using the method to discover hidden vulnerabilities of tumor cells. Doctors are using CRISPR to edit genes that cause hereditary diseases.
The era of human gene editing isn’t coming,” said David Liu, a biologist at Harvard University. “It’s here.”
But CRISPR’s influence extends far beyond medicine. Evolutionary biologists are using the technology to study Neanderthal brains and to investigate how our ape ancestors lost their tails. Plant biologists have edited seeds to produce crops with new vitamins or with the ability to withstand diseases. Some of them may reach supermarket shelves in the next few years.
CRISPR has had such a quick impact that Dr. Doudna and her collaborator, Emmanuelle Charpentier of the Max Planck Unit for the Science of Pathogens in Berlin, won the 2020 Nobel Prize for chemistry. The award committee hailed their 2012 study as “an epoch-making experiment.”
Dr. Doudna recognized early on that CRISPR would pose a number of thorny ethical questions, and after a decade of its development, those questions are more urgent than ever.
Will the coming wave of CRISPR-altered crops feed the world and help poor farmers or only enrich agribusiness giants that invest in the technology? Will CRISPR-based medicine improve health for vulnerable people across the world, or come with a million-dollar price tag?
The most profound ethical question about CRISPR is how future generations might use the technology to alter human embryos. This notion was simply a thought experiment until 2018, when He Jiankui, a biophysicist in China, edited a gene in human embryos to confer resistance to H.I.V. Three of the modified embryos were implanted in women in the Chinese city of Shenzen.
In 2019, a court sentenced Dr. He to prison for “illegal medical practices.” MIT Technology Review reported in April that he had recently been released. Little is known about the health of the three children, who are now toddlers.
Scientists don’t know of anyone else who has followed Dr. He’s example — yet. But as CRISPR continues to improve, editing human embryos may eventually become a safe and effective treatment for a variety of diseases.
Will it then become acceptable, or even routine, to repair disease-causing genes in an embryo in the lab? What if parents wanted to insert traits that they found more desirable — like those related to height, eye color or intelligence?
Françoise Baylis, a bioethicist at Dalhousie University in Nova Scotia, worries that the public is still not ready to grapple with such questions.
“I’m skeptical about the depth of understanding about what’s at issue there,” she said. “There’s a difference between making people better and making better people.
Making the cut
Dr. Doudna and Dr. Charpentier did not invent their gene-editing method from scratch. They borrowed their molecular tools from bacteria.
In the 1980s, microbiologists discovered puzzling stretches of DNA in bacteria, later called Clustered Regularly Interspaced Short Palindromic Repeats. Further research revealed that bacteria used these CRISPR sequences as weapons against invading viruses.
The bacteria turned these sequences into genetic material, called RNA, that could stick precisely to a short stretch of an invading virus’s genes. These RNA molecules carry proteins with them that act like molecular scissors, slicing the viral genes and halting the infection.
As Dr. Doudna and Dr. Charpentier investigated CRISPR, they realized that the system might allow them to cut a sequence of DNA of their own choosing. All they needed to do was make a matching piece of RNA.
To test this revolutionary idea, they created a batch of identical pieces of DNA. They then crafted another batch of RNA molecules, programming all of them to home in on the same spot on the DNA. Finally, they mixed the DNA, the RNA and molecular scissors together in test tubes. They discovered that many of the DNA molecules had been cut at precisely the right spot.
For months Dr. Doudna oversaw a series of round-the-clock experiments to see if CRISPR might work not only in a test tube, but also in living cells. She pushed her team hard, suspecting that many other scientists were also on the chase. That hunch soon proved correct.
In January 2013, five teams of scientists published studies in which they successfully used CRISPR in living animal or human cells. Dr. Doudna did not win that race; the first two published papers came from two labs in Cambridge, Mass. — one at the Broad Institute of M.I.T. and Harvard, and the other at Harvard.
Did you CRISPR that?’
Lukas Dow, a cancer biologist at Weill Cornell Medicine, vividly remembers learning about CRISPR’s potential. “Reading the papers, it looked amazing,” he recalled.
Dr. Dow and his colleagues soon found that the method reliably snipped out pieces of DNA in human cancer cells.
“It became a verb to drop,” Dr. Dow said. “A lot of people would say, ‘Did you CRISPR that?’”
Cancer biologists began systematically altering every gene in cancer cells to see which ones mattered to the disease. Researchers at KSQ Therapeutics, also in Cambridge, used CRISPR to discover a gene that is essential for the growth of certain tumors, for example, and last year, they began a clinical trial of a drug that blocks the gene.
Caribou Biosciences, co-founded by Dr. Doudna, and CRISPR Therapeutics, co-founded by Dr. Charpentier, are both running clinical trials for CRISPR treatments that fight cancer in another way: by editing immune cells to more aggressively attack tumors.
Those companies and several others are also using CRISPR to try to reverse hereditary diseases. On June 12, researchers from CRISPR Therapeutics and Vertex, a Boston-based biotech firm, presented at a scientific meeting new results from their clinical trial involving 75 volunteers who had sickle-cell anemia or beta thalassemia. These diseases impair hemoglobin, a protein in red blood cells that carries oxygen.
The researchers took advantage of the fact that humans have more than one hemoglobin gene. One copy, called fetal hemoglobin, is typically active only in fetuses, shutting down within a few months after birth.
The researchers extracted immature blood cells from the bone marrow of the volunteers. They then used CRISPR to snip out the switch that would typically turn off the fetal hemoglobin gene. When the edited cells were returned to patients, they could develop into red blood cells rife with hemoglobin.
Speaking at a hematology conference, the researchers reported that out of 44 treated patients with beta thalassemia, 42 no longer needed regular blood transfusions. None of the 31 sickle cell patients experienced painful drops in oxygen that would have normally sent them to the hospital.
CRISPR Therapeutics and Vertex expect to ask government regulators by the end of year to approve the treatment.
Other companies are injecting CRISPR molecules directly into the body. Intellia Therapeutics, based in Cambridge and also co-founded by Dr. Doudna, has teamed up with Regeneron, based in Westchester County, N.Y., to begin a clinical trial to treat transthyretin amyloidosis, a rare disease in which a damaged liver protein becomes lethal as it builds up in the blood.
Doctors injected CRISPR molecules into the volunteers’ livers to shut down the defective gene. Speaking at a scientific conference, Intellia researchers reported that a single dose of the treatment produced a significant drop in the protein level in volunteers’ blood for as long as a year thus far.
The same technology that allows medical researchers to tinker with human cells is letting agricultural scientists alter crop genes. When the first wave of CRISPR studies came out, Catherine Feuillet, an expert on wheat, who was then at the French National Institute for Agricultural Research, immediately saw its potential for her own work.
“I said, ‘Oh my God, we have a tool,’” she said. “We can put breeding on steroids.”
At Inari Agriculture, a company in Cambridge, Dr. Feuillet is overseeing efforts to use CRISPR to make breeds of soybeans and other crops that use less water and fertilizer. Outside of the United States, British researchers have used CRISPR to breed a tomato that can produce vitamin D.
Kevin Pixley, a plant scientist at the International Maize and Wheat Improvement Center in Mexico City, said that CRISPR is important to plant breeding not only because it’s powerful, but because it’s relatively cheap. Even small labs can create disease-resistant cassavas or drought-resistant bananas, which could benefit poor nations but would not interest companies looking for hefty financial returns.
Because of CRISPR’s use for so many different industries, its patent has been the subject of a long-running dispute. In 2014, a group led by the Broad Institute filed a lawsuit against a group led by the University of California, where Dr. Doudna carried out her original experiments. The institute argued that its researchers, led by the molecular biologist Feng Zhang, were the first to invent CRISPR gene editing in living cells.
In February of this year, the U.S. Patent Trial and Appeal Board issued what is most likely the final word on this dispute. They ruled in favor of the Broad Institute.
Jacob Sherkow, an expert on biotech patents at the University of Illinois College of Law, predicted that companies that have licensed the CRISPR technology from the University of California will need to honor the Broad Institute patent.
The big-ticket CRISPR companies, the ones that are farthest along in clinical trials, are almost certainly going to need to write the Broad Institute a really big check,” he said.
The original CRISPR system, known as CRISPR-Cas9, leaves plenty of room for improvement. The molecules are good at snipping out DNA, but they’re not as good at inserting new pieces in their place. Sometimes CRISPR-Cas9 misses its target, cutting DNA in the wrong place. And even when the molecules do their jobs correctly, cells can make mistakes as they repair the loose ends of DNA left behind.
A number of scientists have invented new versions of CRISPR that overcome some of these shortcomings. At Harvard, for example, Dr. Liu and his colleagues have used CRISPR to make a nick in one of DNA’s two strands, rather than breaking them entirely. This process, known as base editing, lets them precisely change a single genetic letter of DNA with much less risk of genetic damage.
Liu has co-founded a company called Beam Therapeutics to create base-editing drugs. Later this year, the company will test its first drug on people with sickle cell anemia.
Dr. Liu and his colleagues have also attached CRISPR molecules to a protein that viruses use to insert their genes into their host’s DNA. This new method, called prime editing, could enable CRISPR to alter longer stretches of genetic material.
“Prime editors are kind of like DNA word processors,” Dr. Liu said. “They actually perform a search and replace function on DNA.”
Rodolphe Barrangou, a CRISPR expert at North Carolina State University and a founder of Intellia Therapeutics, predicted that prime editing would eventually become a part of the standard CRISPR toolbox. But for now, he said, the technique was still too complex to become widely used. “It’s not quite ready for prime time, pun intended,” he said.
Advances like prime editing didn’t yet exist in 2018, when Dr. He set out to edit human embryos in Shenzen. He used the standard CRISPR-Cas9 system that Dr. Doudna and others had developed years before.
Dr. He hoped to endow babies with resistance to H.I.V. by snipping a piece of a gene called CCR5 from the DNA of embryos. People who naturally carry the same mutation rarely get infected by H.I.V.
In November 2018, Dr. He announced that a pair of twin girls had been born with his gene edits. The announcement took many scientists like Dr. Doudna by surprise, and they roundly condemned him for putting the health of the babies in jeopardy with untested procedures.
Dr. Baylis of Dalhousie University criticized Dr. He for the way he reportedly presented the procedure to the parents, downplaying the radical experiment they were about to undertake. “You could not get an informed consent, unless you were saying, ‘This is pie in the sky. Nobody’s ever done it,’” she said.
In the nearly four years since Dr. He’s announcement, scientists have continued to use CRISPR on human embryos. But they have studied embryos only when they’re tiny clumps of cells to find clues about the earliest stages of development. These studies could potentially lead to new treatments for infertility.
Bieke Bekaert, a graduate student in reproductive biology at Ghent University in Belgium, said that CRISPR remains challenging to use in human embryos. Breaking DNA in these cells can lead to drastic rearrangements in the chromosomes. “It’s more difficult than we thought,” said Ms. Bekaert, the lead author of a recent review of the subject. “We don’t really know what is happening.”
Still, Ms. Bekaert held out hope that prime editing and other improvements on CRISPR could allow scientists to make reliably precise changes to human embryos. “Five years is way too early, but I think in my lifetime it may happen,” she said.”
Can a ‘Magic’ Protein Slow the Aging Process?
Some scientists want to make 100 the new 50.
“Several years ago, scientists studying aging at the Harvard Stem Cell Institute used a somewhat Frankensteinian technique known as parabiosis — surgically joining a young mouse and an old mouse so that they share blood — to see what would happen to the heart and skeletal muscle tissue. They knew from previous research that putting young blood in old mice caused them to grow biologically younger, and that young mice exposed to old blood aged faster.
The Harvard researchers, Amy Wagers and Dr. Richard Lee, found that the old mouse’s heart tissue had been repaired and rejuvenated, becoming young again. In fact, the size of the old mouse’s heart had reduced to that of a young heart.
“We all wondered, what’s the magic stuff in the blood?” said Lee Rubin, a professor of stem cell and regenerative medicine at Harvard and the co-director of the neuroscience program at the Stem Cell Institute. The “magic” they identified was a protein, GDF11, one of tens of thousands produced in the human body. Dr. Rubin’s lab also found that GDF11 in mice stimulated the growth of new blood vessels in the brain and neurons in the hippocampus, a part of the brain associated with learning and memory. Dr. Wagers’s lab found that GDF11 rejuvenated skeletal muscle tissue, too. The scientists’ discoveries were published in the journals Cell and Science in 2013 and 2014.
The obvious next question: Could GDF11 be harnessed to promote regeneration and repair in humans? In 2017, Drs. Rubin, Wagers and Lee, along with five others, founded the pharmaceutical start-up Elevian with the aim of commercializing GDF11-based therapies to stop, slow or reverse diseases associated with aging. It’s a big step from mice to humans, but one that could have profound consequences.
“We’re interested in proteins like GDF11 that are excreted into the bloodstream because those can cause changes throughout the body,” said Dr. Mark Allen, the chief executive of Elevian. “And those are the kind of changes we want.”
Dr. Allen started his first health care company while in medical school at the University of California, Los Angeles, and he left his residency position in 2000 to start a second. In early 2017, he and his investment partner, Sebastian Giwa, an economist, were looking to start a new one that would develop therapies targeting the degenerative processes involved in aging. They looked at two dozen potential research projects before deciding on GDF11.
I had this idea that aging itself could be a target for therapeutic intervention,” Dr. Allen said, “because if we target one aspect of the aging process, then we have the potential to treat many different diseases.”
The initial research into the rejuvenating properties of GDF11 has gotten some pushback from the scientific community. In 2015, after Dr. Wagers and Dr. Lee had published their results, a group of researchers led by David Glass, the executive director of the Novartis Institutes for Biomedical Research in Cambridge, Mass., at the time, challenged the accuracy of their findings in an article in the journal Cell Metabolism. The Harvard researchers subsequently countered the Novartis team’s findings in another paper published later that year in the journal Circulation Research, in which the Harvard researchers cited a problem with the Novartis team’s findings.
Dr. Glass, who is now at the biotechnology company Regeneron, said in a recent email that he stands by his original work, which showed that GDF11 inhibits, rather than helps, muscle regeneration. But, he added, “our work still leaves open the possibility that there could be positive effects of GDF11 in particular settings.”
Dr. Allen said that since the original controversy, Elevian’s research team has reproduced and extended its original findings in multiple studies, but none have yet been published in peer-reviewed journals. However, institutions unrelated to Elevian have conducted and published many preclinical studies demonstrating the therapeutic efficacy of rGDF11 (the form of GDF11 developed in a lab) in treating age-related diseases.
The company is on track to begin human clinical trials in the first quarter of 2023 and has raised $58 million in two rounds of funding, with another round set for mid-2023.
Elevian is one of many companies racing to find ways to increase the human life span by increasing “health span,” the period of life when a person is in generally good health. This emerging sector of the pharmaceutical industry is often referred to as “longevity therapeutics” and includes companies like Altos Labs, which started in January with $3 billion in funding; Calico Life Sciences at Google; Unity Biotechnology; Alkahest; and Juvenescence. About $2 billion in venture capital was invested in pharmaceutical companies focused on anti-aging in 2021,
according to Longevity Technology, a market research company and investment platform focused on the longevity sector.
For years, researchers have been looking for drugs that can extend life span and health span. The Interventions Testing Program at the National Institutes of Health began testing drugs — some approved by the Food and Drug Administration, some not — in mice 17 years ago to see if these interventions would extend their lives. Dr. Richard A. Miller, a professor of pathology at the University of Michigan and the director of the Paul F. Glenn Center for Biology of Aging Research, said anti-aging therapies are often tested on mice because aging in mice is very similar to aging in humans. “Mice and people share organs, cell biology and most varieties of neurons and neurotransmitters, and they often respond to drugs in similar ways,” he said.
A significant challenge lies ahead for all of these companies: Commercializing a drug for aging is nearly impossible because the F.D.A. doesn’t recognize aging as a disease to be treated. And even if it were considered a disease, the clinical studies required to prove that a treatment for it worked would take many years.
“It is likely that clinical studies to see if some drug slows aging — and thereby delays the many consequences of aging — would take a long time,” Dr. Miller said.
So Elevian’s founders determined that the fastest way to market for GDF11 was to target a specific medical condition.
We thought, what’s the worst disease that has no good treatment and that we could treat for the shortest possible duration and show clinical effects?” Dr. Allen said. “We decided that stroke was the right one to target, because it’s the No. 1 cause of long-term disability with very limited treatment options.”
Dr. Elisabeth Breese Marsh, the medical director of the comprehensive stroke program at Johns Hopkins Bayview Medical Center in Baltimore, said the best treatments for strokes caused by clots (about 87 percent of them) is a type of medication known as tissue plasminogen activators, or tPA, which must be given within 4.5 hours of the stroke, and the surgical removal of large clots.
But according to experts, only about 20 percent of stroke victims receive tPA, either because the stroke is not recognized soon enough or because the patient doesn’t qualify because of pre-existing conditions. Elevian’s researchers said their preclinical (and as yet unpublished) studies have shown that just a few days of treatment with GDF11 can improve recovery after stroke. They have found that GDF11 reduces inflammation, improves metabolism and stimulates the brain to regenerate blood vessels and neurons.
The next big hurdle for Elevian is scaling its manufacturing, which requires specialized equipment and conditions. So much research is being conducted in biotech that contract manufacturers are “full up,” Dr. Allen said. “They are busy with Covid-related work, and there has been a lot of funding in biotech generally,” he added. “So it’s a challenge finding the space that meets our specifications.”
And, like almost all other sectors of the economy, biotech research is facing supply chain issues, which make it harder for Elevian to get some of the basic materials it needs to conduct research. But the company is moving forward as fast as it can, and Dr. Allen said he believed the results of its work would have a profound impact on the way we age and how long we live.
“By targeting fundamental mechanisms of aging, we have the opportunity to treat or prevent multiple aging-related diseases and extend the health span,” he said. “We want to make 100 the new 50.” NYTimes
Inhaled Toxic Particles Take Direct Route From Lungs to Brain
“Inhaling air pollution could result in toxic particles being transported from the lungs to the brain via the bloodstream, ultimately resulting in neurological damage.
Breathing in polluted air could lead to toxic particles being transported from lungs to brain, via the bloodstream – potentially contributing to brain disorders and neurological damage, a new study reveals.
Scientists have discovered a possible direct pathway used by various inhaled fine particles through blood circulation with indications that, once there, the particles stay longer in the brain than in other main metabolic organs.
The scientists revealed they had found various fine particles in human cerebrospinal fluids taken from patients who had experienced brain disorders – uncovering a process which may result in toxic particulate substances ending up in the brain.
The data suggests that up to eight times the number of fine particles may reach the brain by traveling, via the bloodstream, from the lungs than pass directly via the nose – adding new evidence on the relationship between air pollution and detrimental effects of such particles on the brain.”
Air pollution is a cocktail of many toxic components, but particulate matter (PM, especially ambient fine particles such as PM2.5 and PM0.1), are the most concerning in terms of causing detrimental health effects. Ultrafine particles, in particular, are able to escape the body’s protective systems, including sentinel immune cells and biological barriers.
Recent evidence has revealed a strong link between high levels of air pollution and marked neuroinflammation, Alzheimer’s-like changes and cognitive problems in older people and even in children.
The team of scientists discovered that inhaled particles can enter the bloodstream after crossing the air-blood barrier – eventually reaching the brain, and leading to damage of the brain-blood barrier and surrounding tissues as they do so. Once in the brain, the particles were hard to clear and were retained for longer than in other organs.
Their findings offer new evidence in proving the risks from particulate pollution to the central nervous system, but the researchers recommend that more investigation is needed into the mechanics of how inhaled ambient fine particles reach the brain.”
The Ocean’s Biggest Garbage Pile Is Full of Floating Life
Researchers found that small sea creatures exist in equal number with pieces of plastic in parts of the Great Pacific Garbage Patch, which could have implications for cleaning up ocean pollution.
Plastic in the ocean poses a threat to marine life, killing more than a million seabirds every year, as well as more than 100,000 marine mammals, according to UNESCO. Everything from fish to whales can become entangled, and animals often mistake it for food and end up starving to death with stomachs full of plastic.
“In 2019, the French swimmer Benoit Lecomte swam over 300 nautical miles through the Great Pacific Garbage Patch to raise awareness about marine plastic pollution.
As he swam, he was often surprised to find that he wasn’t alone.
“Every time I saw plastic debris floating, there was life all around it,” Mr. Lecomte said.
The patch was less a garbage island than a garbage soup of plastic bottles, fishing nets, tires and toothbrushes. And floating at its surface were blue dragon nudibranchs, Portuguese man-o-wars, and other small surface-dwelling animals, which are collectively known as neuston.
Scientists aboard the ship supporting Mr. Lecomte’s swim systematically sampled the patch’s surface waters. The team found that there were much higher concentrations of neuston within the patch than outside it. In some parts of the patch, there were nearly as many neuston as pieces of plastic.
“I had this hypothesis that gyres concentrate life and plastic in similar ways, but it was still really surprising to see just how much we found out there,” said Rebecca Helm, an assistant professor at the University of North Carolina and co-author of the study. “The density was really staggering. To see them in that concentration was like, wow.”
The findings were posted last month on bioRxiv and have not yet been subjected to peer review. But if they hold up, Dr. Helm and other scientists say, it may complicate efforts by conservationists to remove the immense and ever-growing amount of plastic in the patch.
The world’s oceans contain five gyres, large systems of circular currents powered by global wind patterns and forces created by Earth’s rotation. They act like enormous whirlpools, so anything floating within one will eventually be pulled into its center. For nearly a century, floating plastic waste has been pouring into the gyres, creating an assortment of garbage patches. The largest, the Great Pacific Patch, is halfway between Hawaii and California and contains at least 79,000 tons of plastic, according to the Ocean Cleanup Foundation. All that trash turns out to be a great foothold for living things.
Dr. Helm and her colleagues pulled many individual creatures out of the sea with their nets: by-the-wind sailors, free-floating hydrozoans that travel on ocean breezes; blue buttons, quarter-sized cousins of the jellyfish; and violet sea-snails, which build “rafts” to stay afloat by trapping air bubbles in a soap-like mucus they secrete from a gland in their foot. They also found potential evidence that these creatures may be reproducing within the patch.
“I wasn’t surprised,” said Andre Boustany, a researcher with the Monterey Bay Aquarium in California. “We know this place is an aggregation area for drifting plastics, so why would it not be an aggregation area for these drifting animals as well?”
Little is known about neuston, especially those found far from land in the heart of ocean gyres.
“They are very difficult to study because they occur in the open ocean and you cannot collect them unless you go on marine expeditions, which cost a lot of money,” said Lanna Cheng, a research scientist at the University of California, San Diego.
Because so little is known about the life history and ecology of these creatures, this study, though severely limited in size and scope, offers valuable insights to scientists.
But Dr. Helm said there is another implication of the study: Organizations working to remove plastic waste from the patch may also need to consider what the study means for their efforts.
There are several nonprofit organizations working to remove floating plastic from the Great Pacific Patch. The largest, the Ocean Cleanup Foundation in the Netherlands, developed a net specifically to collect and concentrate marine debris as it is pulled across the sea’s surface by winds and currents. Once the net is full, a ship takes its contents to land for proper disposal.
Dr. Helm and other scientists warn that such nets threaten sea life, including neuston. Although adjustments to the net’s design have been made to reduce bycatch, Dr. Helm believes any large-scale removal of plastic from the patch could pose a threat to its neuston inhabitants.
“When it comes to figuring out what to do about the plastic that’s already in the ocean, I think we need to be really careful,” she said. The results of her study “really emphasize the need to study the open ocean before we try to manipulate it, modify it, clean it up or extract minerals from it.”
Laurent Lebreton, an oceanographer with the Ocean Cleanup Foundation, disagreed with Dr. Helm.
“It’s too early to reach any conclusions on how we should react to that study,” he said. “You have to take into account the effects of plastic pollution on other species. We are collecting several tons of plastic every week with our system — plastic that is affecting the environment.”
Plastic in the ocean poses a threat to marine life, killing more than a million seabirds every year, as well as more than 100,000 marine mammals, according to UNESCO. Everything from fish to whales can become entangled, and animals often mistake it for food and end up starving to death with stomachs full of plastic.
Ocean plastics that don’t end up asphyxiating an albatross or entangling an elephant seal eventually break down into microplastics, which penetrate every branch of the food web and are nearly impossible to remove from the environment.
One thing everyone agrees on is that we need to stop the flow of plastic into the ocean.
“We need to turn off the tap,” Mr. Lecomte said.”
Vaping Alters Inflammatory State of Brain, Heart, Lungs, and Colon
“Researchers at University of California San Diego School of Medicine report that daily use of pod-based e-cigarettes alters the inflammatory state across multiple organ systems including the brain, heart, lungs and colon. Effects also vary depending on the e-cigarette flavor, and can influence how organs respond to infections, such as SARS-CoV-2.
The study, published April 12, 2022 in the journal eLife, is the first to assess JUUL devices and their flavorants in a multi-organ fashion.
“These pod-based e-cigarettes have only become popular in the last five or so years, so we don’t know much about their long-term effects on health,” said senior study author Laura Crotty Alexander, MD, associate professor of medicine at UC San Diego School of Medicine and section chief of Pulmonary Critical Care at Veterans Affairs San Diego Healthcare System.
More than 12 million adults in the United States currently use e-cigarettes, with the highest rates of use among those aged 18-24. Despite their popularity, research on e-cigarettes has been largely limited to studies of short-term use, older devices, such as vape pens or box mods, and e-liquids with significantly lower nicotine concentrations than the modern rechargeable pod-based systems.
Crotty Alexander’s team focused on the current most prominent e-cigarette brand, JUUL, and its most popular flavors: mint and mango. To model chronic e-cigarette use, young adult mice were exposed to flavored JUUL aerosols three times a day for three months. Researchers then looked for signs of inflammation across the body.
Authors saw the most striking effects in the brain, where several inflammatory markers were elevated. Additional changes in neuroinflammatory gene expression were noted in the nucleus accumbens, a brain region critical for motivation and reward-processing.
The findings raise major concerns, they said, as neuroinflammation in this region has been linked to anxiety, depression and addictive behaviors, which could further exacerbate substance use and addiction.
“Many JUUL users are adolescents or young adults whose brains are still developing, so it’s pretty terrifying to learn what may be happening in their brains considering how this could affect their mental health and behavior down the line,” said Crotty Alexander.
Inflammatory gene expression also increased in the colon, particularly after one month of e-cigarette exposure, which could increase risk of gastrointestinal disease. In contrast, the heart showed decreased levels of inflammatory markers. Authors said this state of immunosuppression could make cardiac tissue more vulnerable to infection.
While lungs did not show tissue-level signs of inflammation, numerous gene expression changes were observed in the samples, calling for further study of the long-term effects of pod-based e-cigarettes on pulmonary health.
The researchers also found that the inflammatory response of each organ varied depending on which JUUL flavor was used. For example, the hearts of mice that inhaled mint aerosols were much more sensitive to the effects of bacterial pneumonia compared to those that inhaled mango aerosols.
“This was a real surprise to us,” said Crotty Alexander. “This shows us that the flavor chemicals themselves are also causing pathological changes. If someone who frequently uses menthol-flavored JUUL e-cigarettes was infected with COVID-19, it’s possible their body would respond differently to the infection.”
Every organ has its own finely tuned immune environment, so disturbing that balance through e-cigarette use could lead to many long-term health effects, the authors wrote.
“It’s clear that every e-cigarette device and flavor has to be studied to determine how it affects health across the body,” said Crotty Alexander.”
Stocks resume their rout as falling profits reignite fears of inflation
“A short reprieve for investors ended abruptly on Wednesday as stocks had their worst day yet in a series of already ugly drops after shrinking profits by major retailers reignited Wall Street’s fear of high inflation.
The S&P 500 fell 4 percent, its biggest drop since June 2020 and its fourth decline of more than 3 percent in less than a month, erasing gains in the index since late last week. The tech-heavy Nasdaq composite dropped 4.7 percent.
Retailers led the decline. Target plunged 24.9 percent, making it the worst performer in the S&P 500, after the company reported on Wednesday that high costs affected its profits in its latest quarter. It also lowered its forecast for the year.
The warning echoed a similar report from Walmart, which said on Tuesday that its profit fell 25 percent from a year ago in the quarter and also issued a grim forecast. It was down 6.8 percent on Wednesday after falling more than 11 percent the day before.
Retailers are being pinched by higher costs for fuel after Russia’s invasion of Ukraine, and the sanctions imposed or proposed as a result, caused a jump in oil prices. On Wednesday, futures for oil contracts were slightly lower at about $110 a barrel — but that price was still well above the approximately $78 a barrel crude oil futures traded for at the end of last year. And AAA said gas prices in the United States pushed to a new high on Wednesday — $4.57 on average for a gallon of regular — climbing well above its peak price in March. The average is now above $4 in every state.
Both Target and Walmart said that their sales actually rose slightly as shoppers kept spending even with prices rising across the economy. On Tuesday, the government said consumer spending in the United States continued to climb in April. That eased investors’ concerns about the health of the economy, but the upbeat sentiment didn’t last long.
“Consumers are weathering the inflation hit,” Fiona Cincotta, a senior financial markets analyst at Forex.com, wrote in a note. “Retailers, however, are not doing so well at navigating through 40-year high inflation.”
Rising prices elsewhere may help TJX, which owns discount brands including T.J. Maxx, Marshalls and HomeGoods. It was one of just seven gainers in the S&P 500 on Wednesday, rising 7.1 percent, after it reported that profit rose a better-than-expected 10 percent in the three months through April.
Big swings have come to characterize trading on Wall Street in recent weeks as investors have struggled to face the uncertainty. The Federal Reserve is quickly raising interest rates to combat rapid inflation. And economists are worried that the economy is at risk of a recession because consumer activity could ebb as borrowing costs rise.
Wall Street was anticipating that we were going to see a peak of inflation a month ago,” said Edward Moya, a senior market analyst at Oanda. “Earnings season is telling us that these pricing pressures are not easing and that consumers should expect higher prices moving forward. That will force the Fed into a difficult decision where they might have to tighten more aggressively, and that could weigh on economic growth.”
Jerome H. Powell, the chair of the Fed, said on Tuesday that the central bank would “have to consider moving more aggressively if policymakers don’t see clear indications that inflation is cooling.
The recent volatility has come with the S&P 500 hovering just above bear market territory, or a 20 percent drop from its most recent high. Passing that threshold generally reflects a lasting shift in tone among investors. By Wednesday afternoon, the index was 18.2 percent below its Jan. 3 high and was heading for its seventh consecutive weekly decline, its worst stretch since 2001.
Volatility has also gripped other markets. The rate on 10-year U.S. Treasury notes, a benchmark for borrowing costs across the economy, fell to 2.9 percent on Wednesday after climbing above 3 percent earlier this month, touching its highest level since 2018.”
We pay for “free” services with something more valuable than money: our “privacy”
“Privacy is under assault,” said Fulton, the CEO of Lucidum. It’s a high-value target for malicious hackers, employers, governments, e-commerce sites, and the most prominent “free” software apps and tool providers.
Thousands of laws guard our data, but that doesn’t do the trick, does it?
The internet was considered free for many years until it dawned on us that it is quite the opposite. We pay for “free” services with something more valuable than money – our privacy. Different surveys show that privacy concerns are growing. But if privacy is indeed our crown jewel, why do we still keep trading it for some shiny objects?
Fulton has spent two decades in the cybersecurity industry and held leadership positions at Splunk, Symantec, Google, Starbucks, and Boeing. He believes consumers are still pretty ignorant about the value of their privacy and are willing to discuss the trade-off. I virtually sat down with Fulton to discuss why we keep choosing convenience over privacy over and over again.
We are willing to discuss the trade of some convenience or shiny object for my privacy. Most people don’t value privacy the way I value privacy, so they are more willing to make that trade. Those goods that they receive become something common. I met with some folks in China and privately asked them, ‘tell me your feelings about privacy.’ When you leave a house, you don’t take a wallet, you don’t carry cash, you don’t take house keys, you take your phone because your phone opens the door to the house, your phone is your subway ticket, it’s your fare for the taxi, and everything is on your phone, but your government sees everything you do, is that a concern for you? Their answer was, ‘why wouldn’t the government want to protect me, take care of me, and do what’s right for me? No, I don’t have any concern about them because they are the ones taking care of me.’ There’s a cultural difference wherein, more in the West, we think privacy is good, it’s our right. That’s a very different concept.
people are concerned about privacy. At the same time, they are willing to trade very personal information, for example, from their fitbits, in exchange for cheaper insurance.
I think we focus on the benefit and not on the cost. People will say, and I heard friends of mine, who got to know better, say, ‘well, somebody got this information about me anyway, so I might as well get the reward, having already given that up.’ Do people really care about privacy? I think they do when the consequences of their privacy exposure become real. A cause-and-effect gap prevents people from being vigilant upfront about privacy.
There are three things we do in information security. We protect confidentiality, integrity, and availability. Availability is the system being alive and responsive to the right people. Integrity is that the data on the system reflects what it ought to reflect. So somebody changed your bank balance, for example. Blockchain is a significant step forward in immutable integrity. But confidentiality is the most difficult. If you are at a bank ATM, you enter your PIN, and if I am standing over your shoulder and I spy your PIN, you don’t know your confidentiality has been breached until I violate your bank account.
There’s this gap between your privacy having been exposed and the consequences. That, I think, is where these companies and governments have room to run. When they expose my privacy and abuse it, I don’t know until a negative consequence happens. And that’s so long in that cause and effect cycle that people don’t make the connection that this came because I was on Facebook or because I didn’t change settings on SIRI. They don’t see that.
I am very conscientious about where my data goes. I have never had a Facebook account, and I don’t share private or personal information on Twitter. My behavior is formed by the fact I’ve used peoples’ disclosure of information for security purposes to protect a company or identify where a high net worth family is leaking information that makes them vulnerable. It’s very apparent to me how the stuff could be used.
But it’s really simple things. It wasn’t that long ago, Verizon switched all of its cellphone subscribers from opt-out to opt-in and began collecting information. No notification just made a switch, and you got to dig in your phone to find the settings. Google did the same thing – opening up access to your Google docs to them so they can decide. So just paying attention to these services is number one.
I’m a little more extreme in that I pay for my services. If I pay, I have greater control over my privacy. So instead of Gmail, I use Proton. Instead of G Drive, I’ll use Box or something. It’s a commercial relationship, and I’m not willing to be the pay.”
Antibiotics weakening the natural immune system
The antibiotics: a threat to public health and the natural environment
When an organism’s immune system is weakened, the organism becomes less able to fight viruses and bacteria and thus more prone to diseases.
A common and harmless infections can become life-threatening by irresponsible antibiotics prescriptions.
“Antibiotics have once falsely proclaimed the salvation of the world. Today, researchers fear that antibiotics could become a threat to public health and the natural environment.
Since its invention, because of irresponsibly prescribing by the medical professionals antibiotics have been used in such large doses and so often that more and more of them become resistant, and thus otherwise common and harmless infections can become life-threatening for us.
In recent years, research has also shown that just being exposed to antibiotics can have a negative effect; both on the organism being exposed and on the offspring of the organism.
Always in our water
And both humans and animals are exposed to antibiotics. Antibiotics are often found in wastewater, groundwater, surface water, and even bottled water and are thus difficult not to come into contact with.
“The half-life of antibiotics is quite short – it is out of the water again after hours or days – but since large amounts are continuously released into our water, we consider antibiotics as pseudo persistent water pollution,” says Elvis Genbo who is an expert in ecotoxicology and assistant professor at the Department of Biology, University of Southern Denmark.
He is the co-corresponding author of a new study on the undesirable effects of antibiotics, published in Environmental Science & Technology.
The background for the study is that in recent years, researchers have discovered that antibiotics can have a detrimental effect on the descendants of the individuals exposed to the drugs.
“In this study, we examined the offspring of zebrafish that were exposed to CTC, which is a common antibiotic. The CTC concentrations of the experiment corresponded to the concentrations that wild organisms may encounter in nature.
We can see that the young generations, ie the offspring, are less effective at fighting bacteria and in general have a weaker immune system than the parent generation,” explains Elvis Genbo.
More specifically, the study shows that the first generation of zebrafish, born to CTC-exposed parents, had weakened antibacterial defenses and that the number of their immune cells decreased. The latter also applied to the third generation. When an organism’s immune system is weakened, the organism becomes less able to fight viruses and bacteria and thus more prone to diseases.
Previous research has also shown that males among so-called false scorpions (Cordylochernes scorpioides) have poorer sperm quality when their fathers have been exposed to the antibiotic tetracycline: the number of viable sperm cells fell by 25 percent.
Note: From 2000 to 2015, world consumption of antibiotics increased by 65 percent. from 21.1 billion daily doses to 34.8 billion Every year, more than 700,000 people die as a result of antibiotic resistance; a number expected to rise to 10 million in 2050.”
Genes can affect our nutrient tolerance
“The researchers utilised a genetic reference panel consisting of roughly 200 closely related fruit fly strains (Drosophila melanogaster). The flies were fed six different diets containing high concentrations respectively of protein, sugar, starch, coconut oil or lard, or a combination of sugar and lard. The strains used in the study have had their genomes fully mapped, which made it possible to link the differences seen in the experiments to specific genetic variation.
The study found that small genetic differences affected the flies’ ability to use the energy of various nutrients.
“Unexpectedly we found that the fruit fly strains differed considerably, for example, in their ability to survive on a high-sugar diet. What makes this particularly surprising is the fact that the food consumed by fruit flies in nature contains a lot of sugars,” says Essi Havula, now a postdoctoral researcher at the University of Helsinki and the lead author of the study.
“The genes that regulate metabolism have been conserved well in evolution, which is why we can learn a lot about human metabolism through studies carried out with fruit flies,” Havula adds.
Genetic analyses uncover several genes that affect nutrient tolerance
In genetic analyses, the researchers identified a number of genes that contributed to the ability of flies to tolerate sugar. Most of these genes are found also in humans and have been suggested in previous genome-wide association studies to play a role in obesity and type 2 diabetes.
“Fly studies enable fast and cost-effective functional studies to investigate the genes in depth. Among other things, we demonstrated that the tailless gene (TLX), previously investigated primarily from the perspective of the function and development of the nervous system, is necessary for the normal function of sugar metabolism in flies,” Havula says.
In addition, the researchers demonstrated that the JNK pathway, one of the most important stress-signalling pathways, regulated sugar metabolism and storage-fat synthesis in the case of high-sugar diets in the study.
“It appears that dietary sugar causes stress to the cells, giving the JNK pathway an important role in how effectively flies tolerate and process sugar,” Havula says.
Can nutrigenomics assist the development of personalised nutrition?
According to the researchers, most of the findings can be applied to humans as well, even though further research is still needed. Havula points out that the study provides concrete evidence on how the same dietary recommendations do not necessarily suit everyone.
“Research-based knowledge increasingly shows how metabolic responses to diets differ between animal populations and individuals. Traditional dietary recommendations are not necessarily suited to everyone, which explains the continued lack of consensus on a ‘healthy diet’.”
One option is to develop nutrition in a more personalised direction with the help of nutrigenomics.
“Hopefully, in the future type 2 diabetes and many other metabolic diseases can be treated with nutritional planning based on knowledge of individual genomes. This would be considerably less expensive than drug therapies as well as better for the health of individuals in the long run,” says Havula.
The potential of nutrigenomics is not limited to the treatment of traditional metabolic diseases.
“For example, cancer cells are known to alter their metabolism, extending the potential of nutrigenomics to a wide range of fields,” Havula adds.”
Apple’s privacy changes are expected to wipe almost $16 billion from Meta, YouTube, Snap, and Twitter’s revenues this year
“The fallout from Apple’s major privacy update is expected to continue well past the first year of its rollout, with a new analysis estimating the change could dent Meta, YouTube, Snap, and Twitter’s revenues by almost $16 billion in total this year.
Introduced on April 26 in 2021, the App Tracking Transparency update forced app developers to ask permission before tracking users across other apps and websites using Apples Identifier for Advertisers. With a vast number of users blocking such tracking, advertisers and tech platforms lost a valuable signal that helps them accurately target and measure their ads.
The change forced many advertisers to reassess their marketing and shift spend into channels that are less reliant on Apple’s tracking identifier, such as offline advertising or Apple’s own search ad products.
New analysis from data management company Lotame, shared exclusively with Insider, estimates that Facebook owner Meta will continue to feel the biggest brunt of Apple’s privacy changes in 2022. Lotame estimates that the change will cause a $12.8 billion hit to Meta’s 2022 revenue, or 9.7%.
Meta warned last year that Apple’s privacy change would create a headwind “on the order of $10 billion” in 2022. The company, like other tech platforms, has been working to introduce new privacy focused measurement and optimization tools to mitigate the effects of the Apple update – though any new tools take a while for advertisers to get up to speed with.
Snap, whose business is almost exclusively focused on mobile, is estimated to feel a similar pinch to its revenue this year — though much smaller in dollar terms. Lotame estimates Snap will take a 9.6% hit to its 2022 revenue, equivalent to about $546 million.
The Snapchat owner had attributed Apple’s privacy changes and supply chain shortages in part to its third-quarter revenue miss in 2021. The company appeared to have recovered in the following quarter, posting its first quarterly profit.
Snap CFO Derek Andersen said in February that while advertisers had begun to recover from the initial disruption from the ATT rollout in the fourth quarter, it would still take “at least a couple more quarters” before marketers adapted to its new measurement and targeting tools.
Google parent Alphabet has a huge ad business of its own, with a ton of data about its swathes of users and a search ads product that didn’t feel the effects of the changes. It also owns the Android operating system that still has an identifier intact, so it reaped the benefits of advertisers shifting away from targeting iOS users. However, the company said last year that Apple users opting out of tracking would have a “modest impact” on YouTube’s revenue.
Lotame estimates that “modest impact” will hit YouTube to the tune of $2.2 billion, or 6.5% of its revenue in 2022.
Twitter has also previously said the impact from ATT has been “modest” and would continue to be so through to the first quarter of 2022. The company has said that investments in product improvements made in 2020 and 2021 had paid off. Plus, the company is more focused on brand advertising — designed to pitch a brand to large audience rather than eliciting a direct response — than many of its counterparts.
Lotame estimated that Apple’s privacy update will impact Twitter’s 2022 revenue by $323 million, or 5.4% of its revenue.
Spokespeople for Apple, Meta, Alphabet, Twitter, and Snap either declined to comment or didn’t immediately respond to requests for comment.
Lotame’s analysis pulled in factors including each platform’s dependence on mobile, their share of iOS users, a 65% average consumer opt-out rate from tracking, and an analysts’ consensus forecast of each company’s 2022 revenue. Given that each platform is still growing at a considerable rate year-on-year, the impact is likely to be reflected in a slowdown in future growth as opposed to a direct setback in topline sales.
Lots could still change. Experts predict that Apple could further disrupt the advertising landscape by enhancing its privacy tools. Meanwhile, the platforms could be affected by supply chain disruptions and other macroeconomic events. Plus, the tech giants are leaning heavily into e-commerce as a way to conduct sales entirely within their own platforms, without the need to rely on third-parties for measurement. Meanwhile, the industry is gearing up for further tracking changes, from Google’s move to kill cookies in Chrome, to upcoming new global privacy regulations.
“As the year progresses, the impact of this particular change will be harder and harder to isolate and will start to get stirred in with other changes that might occur around accessibility to formerly more open media systems,” said Lotame’s chief operating officer.
Lotame carried out a similar analysis in October last year and estimated Meta, YouTube, Snap, and Twitter lost $9.85 billion in revenue as a result of Apple’s privacy changes in the second half of 2021, The Financial Times reported.”
In Europe, It’s Planes vs. Trains.
For Many Travelers, Rail Is the Way to Go.
Amid concerns about climate change, Europe is investing heavily in trains. The idea is to make rail more appealing, especially as an alternative to short-haul flights.
“People are fed up with the airport and airline experience — they want something less stressful and more interesting . And they want to cut their carbon footprint.”
“Train travel in Europe is on the upswing, thanks to growing interest from travelers, a renaissance in sleeper trains, and new investments in high-speed rail lines across the continent. But to see major growth in passenger traffic — which is one of the goals of the European Green Deal — the continent’s railways will have to overcome a number of challenges, including booking difficulties and competition with short-haul flights, which remain the cheaper option on many multicountry routes.
In France and Austria, the pandemic brought the planes-versus-trains question to the forefront. The French government’s Covid bailout package of Air France required the airline to eliminate domestic flights when there was a rail option that took under two and a half hours to complete; the measure was later written into law.
The Austrian government placed a similar condition on its support to Austrian Airlines, demanding that the company end its 50-minute flight between Vienna and Salzburg, a journey that passengers can make by train in about three hours.
The European Commission also designated 2021 as the “Year of European Rail,” seizing the opportunity to spread the word about train travel, particularly to a younger audience. While passenger traffic was growing steadily through 2019, it was starting from a low base: Before the pandemic, only 8 percent of all passenger travel in the European Union was by train.
But in addition to the public relations campaign, European leaders are also working to reduce practical barriers to cross-border train travel by introducing new data-sharing systems, replacing outdated infrastructure, and building new high-speed routes, particularly in Central and Eastern Europe.
“The idea is that for train trips of less than four hours, no businesspeople will choose to fly, and for trips below six hours, normal people — tourists — will take the train,” said Alberto Mazzola, the executive director of the Community of European Railways and Infrastructure Companies, which is based in Brussels. Mr. Mazzola added that government leaders are throwing their weight behind railway infrastructure, particularly high-speed lines. “We heard this 20 years ago,” he added. “The difference today is that we are seeing the investments.”
Night trains on the rise
Europe’s night trains are a big part of the rising tide of rail on the continent. On the decline since the 1990s, overnight services suffered alongside the growth of low-cost air carriers and a rise in government investment in high-speed trains, whose faster daytime services often displaced their slower nighttime counterparts. But that trend was already starting to shift before the pandemic and now the momentum behind night trains appears to be building fast, with new sleeper connections cropping up across the continent.
“It’s true that we have a real revival of night trains in France and in Europe,” said Alain Krakovitch, the director of travel at SNCF, France’s state-owned railway company. “It is a very strong demand, both from customers, but also from elected officials, mayors and the government.”
Last year, SNCF relaunched overnight services between Paris and Nice, with tickets starting as low as 19 euros, about $21, for a midweek low-season ticket. That compares with 31 euros, not including baggage fees or the cost of airport transfers, for a short flight on EasyJet leaving on a similar day. SNCF also offers overnight services between Paris and Toulouse, and between Paris and Lourdes in southwestern France. A and Lourdes in southwestern France. A night train to Hendaye, a French coastal town near the Spanish border, will run in July and August. And change-free overnight service between Paris and Berlin — a journey that currently takes eight hours and requires at least one change — is scheduled to begin in December 2023, as a cooperative effort between four European operators.
So far, said Mr. Krakovitch, demand has been strong.
“It’s true that this is a huge draw for passengers. The idea of being able to fall asleep in Paris and wake up in Nice saves a night in a hotel,” said Mr. Krakovitch. “It allows you to arrive very early in Nice without being tired. It’s a product that has many benefits, but we had to invest heavily to relaunch it. We hope to keep this momentum going.”
It’s a similar story elsewhere in Europe. Last year, the Swiss Federal Railways launched a new overnight connection from Zürich to Amsterdam (with stops in Basel and Cologne), adding to overnight services connecting Switzerland’s largest city to Berlin, Budapest, Prague and Zagreb, among other destinations. European Sleeper, a Dutch-Belgian company founded by two entrepreneurs, is planning an overnight connection between Brussels and Prague, with stops in Amsterdam and Berlin, among other cities; they hope to launch the service this summer, but the start date is not yet confirmed.
Meanwhile, the Austrian operator ÖBB’s Nightjet service has recently begun offering an overnight link between Vienna and Paris, with tickets ranging from about 30 euros for a normal train seat, to 200 euros or higher, depending on the date of travel, for a first-class private cabin. (A midweek, low-season flight on the same route costs 44 euros, not including baggage fees, on the low-cost carrier Transavia.)
Nightjet, which also runs overnight services to cities like Rome, Milan, Brussels and Amsterdam, is offering passengers more options to book private compartments, a Nightjet spokesman said, adding that some cabins have a private shower and toilet. The prices scale with the amenities provided: A couple traveling overnight from Vienna to Amsterdam on a weeknight in July, for instance, can book two seats in a private compartment for a total of 129 euros. Alternatively, they could opt for a two-bed sleeper cabin for 378 euros for both travelers, including breakfast. Add a private shower and toilet and the price rises to 418 euros. At the moment, all of the Nightjet “rolling stock” is in use, but new services should be coming online in the years ahead, the spokesman said. More than 30 new sleeper trains should be delivered beginning in 2023.
But while night trains are offering new connections for travelers, they serve only specific routes. People who are looking to make connections between cities that aren’t linked on those networks continue to face challenges, both in booking their tickets and in the prices they are charged. Some long-distance journeys with multiple stops are still much cheaper by plane than by train.
The fact remains that, despite the European Union’s support for rail, the bloc’s governments continue to grant enormous subsidies to airlines — in the form of bailout packages as well as low taxes on jet fuel — although that could change soon. And while the French and Austrian bans on short-haul flight bans attracted attention in Europe, in effect, the measures ended flights on just one route — Vienna to Salzburg — in Austria, and three in France: Paris to Bordeaux, Paris to Lyons, and Paris to Nantes. In the French case, passengers are still allowed to fly those routes if they make up part of a longer plane journey.
Herwig Schuster, a transport campaigner for Greenpeace’s E.U. Mobility for All campaign, called the French and The fact remains that, despite the European Union’s support for rail, the bloc’s governments continue to grant enormous subsidies to airlines — in the form of bailout packages as well as low taxes on jet fuel — although that could change soon. And while the French and Austrian bans on short-haul flight bans attracted attention in Europe, in effect, the measures ended flights on just one route — Vienna to Salzburg — in Austria, and three in France: Paris to Bordeaux, Paris to Lyons, and Paris to Nantes. In the French case, passengers are still allowed to fly those routes if they make up part of a longer plane journey.
Herwig Schuster, a transport campaigner for Greenpeace’s E.U. Mobility for All campaign, called the French and Austrian measures “a starting point” and said the European Union should prohibit flights for which there is a train alternative that takes under six hours, instead of just two or three. Such a measure would eliminate about one third of Europe’s most popular short-haul routes, but Mr. Schuster maintained that consumers are ready for such a shift: A recent climate survey found that 62 percent of Europeans support a ban on short-haul flights. The biggest obstacle, he added, would be making sure that rail options are at least as affordable as flights. On several European routes — especially longer-distance trips that cross multiple national borders — flying remains the cheaper option: A one-way, midweek flight from Zürich to Barcelona in July costs as little as 45 euros on the low-cost carrier Vueling, compared with 140 euros (and many more hours) to cover the same distance by rail. Flying is also usually the more affordable option for trips from London to Madrid, Copenhagen to Rome, and Paris to Budapest.
The fact that Europe’s vast rail network lacks a single ticketing system presents another challenge, said Mark Smith, who runs The Man in Seat 61, a website with resources for train travel in Britain, Europe and around the world. But he said that in many cases, trains are a good value compared with planes, especially when you account for baggage fees and the cost of getting to and from the airport. Booking in advance, just as you would for a flight, can also save travelers a lot of money, Mr. Smith said, adding that he advises people to reserve their long-distance train travel one to three months ahead to avoid last-minute price hikes. He also recommends sites like Trainline and Rail Europe for booking multicountry trips in Europe.
He added that many travelers still opt for the train, even if, in some cases, it does mean paying more for their ticket. When he started his site 20 years ago, Mr. Smith said, most people he spoke to who were interested in long-distance train travel were either scared of flying or unable to fly for medical reasons. These days, he hears a different rationale.
“People are fed up with the airport and airline experience — they want something less stressful and more interesting,” he said. “And they want to cut their carbon footprints.” NY Times
In the Ocean,
It’s Snowing Micro plastics
A recent model found that 99.8 percent of plastic that entered the ocean since 1950 had sunk below the first few hundred feet of the ocean. Scientists have found 10,000 times more microplastics on the seafloor than in contaminated surface waters.
Tiny bits of plastic have infiltrated the deep sea’s main food source and could alter the ocean’s role in one of Earth’s ancient cooling processes, scientists say.
“As long as there has been marine life, there has been marine snow — a ceaseless drizzle of death and waste sinking from the surface into the depths of the sea.
The snow begins as motes, which aggregate into dense, flocculent flakes that gradually sink and drift past the mouths (and mouth-like apparatuses) of scavengers farther down. But even marine snow that is devoured will most likely be snowfall once more; a squid’s guts are just a rest stop on this long passage to the deep.
Although the term may suggest wintry whites, marine snow is mostly brownish or grayish, comprising mostly dead things. For eons, the debris has contained the same things — flecks from plant and animal carcasses, feces, mucus, dust, microbes, viruses — and transported the ocean’s carbon to be stored on the seafloor. Increasingly, however, marine snowfall is being infiltrated by microplastics: fibers and fragments of polyamide, polyethylene and polyethylene terephthalate. And this fauxfall appears to be altering our planet’s ancient cooling process.
Every year, tens of millions of tons of plastic enter Earth’s oceans. Scientists initially assumed that the material was destined to float in garbage patches and gyres, but surface surveys have accounted for only about one percent of the ocean’s estimated plastic. A recent model found that 99.8 percent of plastic that entered the ocean since 1950 had sunk below the first few hundred feet of the ocean. Scientists have found 10,000 times more microplastics on the seafloor than in contaminated surface waters.
Marine snow, one of the primary pathways connecting the surface and the deep, appears to be helping the plastics sink. And scientists have only begun to untangle how these materials interfere with deep-sea food webs and the ocean’s natural carbon cycles.
“It’s not just that marine snow transports plastics or aggregates with plastic,” Luisa Galgani, a researcher at Florida Atlantic University, said. “It’s that they can help each other get to the deep ocean.”
The sunlit surface of the sea blooms with phytoplankton, zooplankton, algae, bacteria and other minuscule life, all feeding on sunbeams or one another. As these microbes metabolize, some produce polysaccharides that can form a sticky gel that attracts the lifeless bodies of tiny organisms, small shreds of larger carcasses, shells from foraminifera and pteropods, sand and microplastics, which stick together to form larger flakes. “They are the glue that keeps together all the components of marine snow,” Dr. Galgani said.
Marine snowflakes fall at different rates. Smaller ones have a more languid descent — “as slow as a meter a day,” said Anela Choy, a biological oceanographer at Scripps Institution of Oceanography at the University of California, San Diego. Bigger particles, such as dense fecal pellets, can sink quicker. “It just skyrockets to the bottom of the ocean,” said Tracy Mincer, a researcher at Florida Atlantic University.
Plastic in the ocean is constantly being degraded; even something as big and buoyant as a milk jug will eventually shed and splinter into microplastics. These plastics develop biofilms of distinct microbial communities — the “plastisphere,” said Linda Amaral-Zettler, a scientist at the Royal Netherlands Institute for Sea Research, who coined the term. “We sort of think about plastic as being inert,” Dr. Amaral-Zettler said. “Once it enters the environment, it’s rapidly colonized by microbes.”
Microplastics can host so many microbial hitchhikers that they counteract the natural buoyancy of the plastic, causing their raft to sink. But if the biofilms then degrade on the way down, the plastic could float back up, potentially leading to a yo-yoing purgatory of microplastics in the water column. Marine snow is anything but stable; as flakes free-fall into the abyss, they are constantly congealing and falling apart, rent by waves or predators.
“It’s not as simple as: Everything’s falling all the time,” said Adam Porter, a marine ecologist at the University of Exeter. “It’s a black box in the middle of the ocean, because we can’t stay down there long enough to work out what’s going on.”
To explore how marine snow and plastics are distributed in the water column, Dr. Mincer has begun to sample deeper waters with a dishwasher-size pump full of filters that dangles on a wire from a research boat. The filters are arranged from big mesh to small to filter out fish and plankton. Running these pumps for 10 hours at a stretch has revealed nylon fibers and other microplastics distributed throughout the water column below the South Atlantic subtropical gyre.
But even with a research boat and its expensive and unwieldy equipment, an individual piece of marine snow is not easily retrieved from deep water in the actual ocean. The pumps often disturb the snow and scatter fecal pellets. And the flakes alone offer little insight into how fast some snows are sinking, which is vital to understanding how long the plastics linger, yo-yo or sink in the water column before settling on the seafloor.
“Is it decades?” Dr. Mincer asked. “Is it hundreds of years? Then we can understand what we’re in here for, and what kind of problem this really is.”
To answer these questions, and work within a budget, some scientists have made and manipulated their own marine snow in the lab.
Dr. Porter collected buckets of seawater from a nearby estuary and loaded the water into continuously rolling bottles. He then sprinkled in microplastics, including polyethylene beads and polypropylene fibers. The constant churning, and a squirt of sticky hyaluronic acid, encouraged particles to collide and stick together into snow.
“We obviously don’t have 300 meters of a tube to make it sink,” Porter said. “By rolling it, what you’re doing is you’re creating a never-ending water column for the particles to fall through.”
After the bottles rolled for three days, he pipetted out the snow and analyzed the number of microplastics in each flake. His team found that every type of microplastic they tested aggregated into marine snow, and that microplastics such as polypropylene and polyethylene — normally too buoyant to sink on their own — readily sank once incorporated into marine snow. And all the marine snow contaminated with microplastics sank significantly faster than the natural marine snow.
Porter suggested that this potential change of the speed of the snow could have vast implications for how the ocean captures and stores carbon: Faster snowfalls could store more microplastics in the deep ocean, whereas slower snowfalls could make the plastic-laden particles more available to predators, potentially starving food webs deeper down. “The plastics are a diet pill for these animals,” said Karin Kvale, a carbon cycle scientist at GNS Science in New Zealand.
In experiments in Crete, with funding from the European Union’s Horizon 2020 research program, Dr. Galgani has tried mimicking marine snow on a larger scale. She dropped six mesocosms — huge bags that each contained nearly 800 gallons of seawater and recreated natural water movement — in a large pool. Under these conditions, marine snow formed. “In the field, you mostly make observations,” Dr. Galgani said. “You have so little space and a limited system. In the mesocosm, you are manipulating a natural system.”
Dr. Galgani mixed microplastics into three mesocosms in an attempt to “recreate a sea and maybe a future ocean where you can have a high concentration of plastic,” she said. The mesocosms laden with microplastics produced not just more marine snow but also more organic carbon, as the plastics offered more surfaces for microbes to colonize. All this could seed the deep ocean with even more carbon and alter the ocean’s biological pump, which helps regulate the climate.
“Of course, it’s a very, very big picture,” Galgani said. “But we have some signals that it can have an effect. Of course, it depends on how much plastic there is.”
Every 24 hours, many species of marine organism embark on a synchronized migration up and down in the water column. “They do the equivalent of a marathon every day and night,” Dr. Choy said. Guilherme V.B. Ferreira, a researcher at the Rural Federal University of Pernambuco in Brazil, wondered: “Is it possible they are transporting the plastics up and down?”
Dr. Ferreira and Anne Justino, a doctoral student at the same university, collected vampire squids and midwater squids from a patch of the tropical Atlantic. They found a plethora of plastics in both species: mostly fibers, but also fragments and beads.
This made sense for midwater squids, which migrate toward the surface at night to feed on fish and copepods that eat microplastics directly. But vampire squids, which live in deeper waters with fewer microplastics, had even higher levels of plastic, as well as foam, in their stomachs. The researchers hypothesize that the vampire squids’ primary diet of marine snow, especially meatier fecal pellets, may be funneling plastics into their bellies.
“It’s very concerning,” Ms. Justino said. Dr. Ferreira said: “They are one of the most vulnerable species for this anthropogenic influence.”
Ms. Justino has excavated fibers and beads from the digestive tracts of lanternfish, hatchetfish and other fish that migrate up and down in the mesopelagic, 650 to 3,300 feet down. Some microbial communities that settle on microplastics can bioluminesce, drawing in fish like a lure, said Dr. Mincer.
In the Monterey Bay Canyon, Choy wanted to understand if certain species of filter feeders were ingesting microplastics and transporting them into food webs in deeper water. “Marine snow is one of the major things that connects food webs across the ocean,” she said.
Choy zeroed in on the giant larvacean Bathochordaeus stygius. The larvacean resembles a tiny tadpole and lives inside a palatial bubble of mucus that can reach up to a meter long. “It’s worse than the grossest booger you’ve ever seen,” Dr. Choy said. When their snot-houses become clogged from feeding, the larvaceans move out and the heavy bubbles sink. Choy found that these palaces of mucus are crowded with microplastics, which are funneled to the deep along with all their carbon.
Giant larvaceans are found across the world’s oceans, but Choy emphasized that her work was focused on the Monterey Bay Canyon, which belongs to a network of marine protected areas and is not representative of other, more polluted seas. “It’s one deep bay on one coast of one country,” Dr. Choy said. “Scale up and think about how vast the ocean is, especially the deep water.”
Individual flakes of marine snow are small, but they add up. A model created by Dr. Kvale estimated that in 2010, the world’s oceans produced 340 quadrillion aggregates of marine snow, which could transport as many as 463,000 tons of microplastics to the seafloor each year.
Scientists are still exploring exactly how this plastic snow is sinking, but they do know for sure, Dr. Porter said, that “everything eventually sinks in the ocean.” Vampire squids will live and die and eventually become marine snow. But the microplastics that pass through them will remain, eventually settling on the seafloor in a stratigraphic layer that will mark our time on the planet long after humans are gone.” NYTimes
Quality Sleep is important, NOT Quantity
Quality sleeping creates resilience and resistance to neurodegenerative conditions that may point the way to fending off neurological disease.
“Some people are gifted with genes that pack the benefits of slumber into an efficient time window, keeping them peppy on only four or six hours of sleep a night, according to researchers at UC San Francisco. In addition, the scientists said, these “elite sleepers” show psychological resilience and resistance to neurodegenerative conditions that may point the way to fending off neurological disease.
“There’s a dogma in the field that everyone needs eight hours of sleep, but our work to date confirms that the amount of sleep people need differs based on genetics,” said neurologist Louis Ptacek, MD, one of the senior authors on the study, which appears in iScience on March 15, 2022 “Think of it as analogous to height; there’s no perfect amount of height, each person is different. We’ve shown that the case is similar for sleep.”
For over a decade, Ptacek and co-senior author both members of the UCSF Weill Institute for Neurosciences, have been studying people with Familial Natural Short Sleep (FNSS), the ability to function fully on—and have a preference for—four to six hours of sleep a night. They’ve shown that it runs in families and, thus far have identified five genes across the genome that play a role in enabling this efficient sleep. There are still many more FNSS genes to find, the researchers said.
This study tested the researchers’ hypothesis that elite sleep can be a shield against neurodegenerative disease. Her ideas contrast somewhat with current thinking that, for many people, lack of sleep can accelerate neurodegeneration. The difference is that with FNSS, the brain accomplishes its sleep tasks in a shorter time. In other words, less time spent efficiently sleeping may not equate to a lack of sleep.
The team chose to look at mouse models of Alzheimer’s disease because that condition is so prevalent. They bred mice that had both short-sleep gene and genes that predisposed them to Alzheimer’s and found that their brains developed much less of the hallmark aggregates associated with dementia. To confirm their findings, they repeated the experiment using mice with a different short-sleep gene and another dementia gene and saw similar results.
The scientists believe that similar investigations of other brain conditions would show the efficient-sleep genes conferring comparable protections. improving peoples’ sleep could delay progression of disease across a whole spectrum of conditions, they said.
Sleep problems are common in all diseases of the brain,” she said. “This makes sense because sleep is a complex activity. Many parts of your brain have to work together for you to fall asleep and to wake up. When these parts of the brain are damaged, it makes it harder to sleep or get quality sleep.”
Understanding the biological underpinnings of sleep regulation could identify drugs that will help ward off problems with sleep disorders. In addition, improving sleep in healthy people may sustain wellbeing and improve the quality of time we each have, the researchers said. But pursuing the many genes involved is a long game that they liken to putting together a thousand-piece jigsaw puzzle.
Every mutation we find is another piece,” said Ptacek. “Right now we’re working on the edges and the corners, to get to that place where it’s easier to put the pieces together and where the picture really starts to emerge.“
Despite the long road ahead, there’s already promise in some of the few genes they’ve identified. At least one of them can be targeted with existing drugs that might be repurposed. Their hope is that within the next decade, they’ll have helped facilitate new treatments that allow people with brain disorders to get a better night’s rest.
This work opens the door to a new understanding of how to delay and possibly prevent a lot of diseases, Our goal really is to help everyone live healthier and longer through getting optimum sleep.”
Australia’s Clever Birds Did Not Consent to This Science Experiment
The magpies showed their smarts by helping one another remove tracking harnesses that scientists carefully placed on them.
Are birds more clever than us?!
“The Australian magpie is one of the cleverest birds on earth. It has a beautiful song of extraordinary complexity. It can recognize and remember up to 30 different human faces.
But Australians know magpies best for their penchant for mischief. An enduring rite of passage of an Australian childhood is dodging the birds every spring as they swoop down to attack those they view as a threat.
Magpies’ latest mischief has been to outwit the scientists who would study them. Scientists showed how clever magpies really are and, in the process, revealed a highly unusual example in nature of birds helping one another without any apparent tangible benefit to themselves.
In 2019 Dominique Potvin, an animal ecologist at University of the Sunshine Coast in Australia, set out to study magpie social behavior. She and her team spent around six months perfecting a harness that would carry miniature tracking devices in a way that was unintrusive for magpies. They believed it would be nearly impossible for magpies to remove the harnesses from their own bodies.
Dr. Potvin and her team attached the tracking devices and the birds flew off, showing no signs of obvious distress. Then everything began to unravel.
“The first tracker was off half an hour after we put it on,” she said. “We were literally packing up our gear and watching it happen.”
In a remarkable act of cooperation, the magpie wearing the tracker remained still while the other magpie worked at the harness with its beak. Within 20 minutes, the helping magpie had found the only weak point — a single clasp, barely a millimeter long — and snipped it with its beak. Dr. Potvin and her team later saw different magpies removing harnesses from two other birds outfitted with them.
The scientists took six months to reach this point. Within three days, the magpies had removed all five devices.
“At first it was heartbreaking,” Dr. Potvin said, “but we didn’t realize how special it was. We went back to the literature and asked ourselves, ‘What did we miss?’ But there was nothing because this was actually new behavior.”
The only similar example of what Dr. Potvin described as “altruistic rescue behavior” — where birds help other birds without receiving tangible benefits in return — was when Seychelles warblers helped other members of their social group escape from sticky seed clusters in which they had become entangled.
The magpies’ behavior was, Dr. Potvin said, “a special combination of helping but also problem solving, of being really social and having this cognitive ability to solve puzzles.”
“It’s probably partly why they’re so successful in our changing environment on farms and in urban areas,” she said. “They’ve managed to figure things out in a new way.”
The Australian magpie is a large black-and-white perching songbird, or passerine, that inhabits nearly 90 percent of mainland Australia. It is a common presence in parks and backyards across the country.
Remarkably, magpies can recognize the faces of as many as 30 people, which is the average number who live within a magpie’s territory. “Very rarely do magpies attack more than one or two people,” said Darryl Jones, a magpie expert at Griffith University. “It’s the same individual people that they attack each time.”
And magpies have long memories: One of Dr. Jones’s research assistants was attacked upon his return after 15 years away from one bird’s territory.
As Sean Dooley, the public affairs manager of Birdlife Australia, put it, “If you think it’s personal, you’re right.” More than 30 people pass through a bird’s territory, “they actually start stereotyping people,” Mr. Dooley said.
He added, “People who resemble 10-year-old boys are much more likely to be swooped, because those are the kids who are more likely to be throwing sticks and stones, shouting and chasing and running at magpies.”
Dr. Jones calls the magpies’ “gorgeous, glorious caroling song” another example of their intelligence.
With more than 300 separate elements, he said, “it’s unbelievably complex. In order to remember and repeat a song of that complexity every single morning without error, you have to have a big brain.”
Dr. Potvin and her team have shelved their original study. But they can’t help but ponder a bigger question: “What else are magpies capable of?” NY Times
Scientists and Noble laureates using cellular rejuvenation to prevent aging
Izpisua: ‘Within two decades, we will be able to prevent aging’
“For the first few days, the young cells of a tiny human embryo are able to turn into any kind of tissue, but they quickly start to specialize in order to create the different organs of the body. This process can be reversed. Human cells can be rejuvenated in the laboratory.”
The researchers were able to revert adult cells in living mice into embryonic stem cells, opening the door for the regeneration of damaged organs. The problem of their pioneering work, however, was that the mice developed multiple tumors.
The leading Spanish scientist talks to EL PAÍS about his new role at the secretive multinational Altos Labs, where he hopes to use cellular rejuvenation to reverse illness and cell deterioration
“In the past few months, a new US company, with a staggering initial budget of €2.7 million ($2.94 million), has been secretly signing up some of the best scientists in the world, including four Noble laureates. When Altos Labs finally launched on January 19, it declared its goal was to enable humans to live longer, healthier lives. It did not reveal who is funding the project, but some reports – neither confirmed nor denied – suggest that a large part of the money is coming from the richest man in the world, Amazon founder Jeff Bezo. The British newspaper The Times led with the headline: “Jeff Bezos recruits in quest for eternal youth.”
Spanish scientist Juan Carlos Izpisua is one of the high-profile names to be hired by Altos Labs. The 61-year-old researcher, who was born in the Spanish town of Hellín in the northern Castilla-La Mancha region, denies that the project is just the whim of a billionaire who wants to be immortal. “That is simply not true. Our interest is in advancing in this area of knowledge and opening the field as wide as possible, so that, over time, everyone can benefit,” he tells EL PAÍS. The company will establish three institutes: one in the US city of San Diego, which will be led by Izpisua, one in Cambridge in the United Kingdom, and another in San Francisco.
The multinational is enveloped in secrecy. This newspaper requested to speak with four of the Spanish scientists recruited by Altos, but the company only approved an interview with Izpisua, who responded to EL PAÍS’ questions by email. “The idea behind our investigations is not so that human beings live 100 or 1,000 years more. If we are able to prolong life without improving the quality of these years, not only would it be morally questionable, but also I would question what purpose it would serve,” says Izpisua. “Our main goal is to enable people to have a healthier life for a longer period of time and to reverse illness in patients of all ages.”
In addition to Izpisua, the leadership team of Altos includes four Nobel laureates: chemist Jennifer Doudna, (2020 Nobel Prize for chemistry), engineer Frances Arnold (2018 Nobel Prize for chemistry), virologist David Baltimore (1975 Nobel Prize for medicine) and Shinya Yamanaka (2012 Nobel Prize for medicine).
For the first few days, the young cells of a tiny human embryo are able to turn into any kind of tissue, but they quickly start to specialize in order to create the different organs of the body. Yamanaka discovered that this process could be reversed. In 2006, he invented a technique to revert adult cells to their embryonic state. His work revealed that cells can be rejuvenated in the laboratory, largely thanks to the activation of four genes that are responsible for the production of four reprogramming molecules, which are known as Yamanaka factors.
The cellular reprogramming will be one of the main lines of investigation at Altos. The company has also hired Spanish scientists Manuel Serrano and María Abad, who in 2013 applied Yamanaka’s technique in animals for the first time. The researchers were able to revert adult cells in living mice into embryonic stem cells, opening the door for the regeneration of damaged organs. The problem of their pioneering work, however, was that the mice developed multiple tumors.
Izpisua’s team at the Salt Institute in the US was able to avoid this problem in 2016, by activating the four rejuvenating genes intermittently, instead of constant programming. In this case, the mice lived 30% longer, even though they had been genetically modified to age prematurely in order to speed up the experiment. On Monday, Izpisua presented the latest results of the study in the specialist journal Nature Aging. His research team and other scientists from the biotech company Genentech intermittently activated the four genes in middle-aged healthy mice for a period equivalent to 35 human years. This partial reprogramming led “to rejuvenating effects in different tissues, such as the kidney and skin,” according to the study. Similar findings were made by Manuel Serrano’s team at Barcelona’s Institution of Biomedicine Research, and published in the journal Aging Cell.
We can program and rejuvenate the tissues and organs of animals with different pathologies, as well as rejuvenate their cells,” explains Izpisua. “Conceptually, I find no reason that stops us from thinking that similar results cannot be achieved in humans, both with respect to improving the course of many diseases and with the rise in the length and quality of life. Indeed, we have already demonstrated this with in vitro human cells.”
For Izpisua’s latest study in Nature Aging, his research team came up with an ingenious experiment. The mice are genetically modified to have additional copies of the four rejuvenating genes, which are only activated if the animal drinks water with the antibiotic doxycycline. This drug acts as an interrupter to either increase or reduce the Yamanaka factors. It’s impossible to carry out the same experiment on humans, but Izpisua is planning similar research on monkeys. In this case, his team will try to rejuvenate the animals by partially programming the Yamanaka factors with RNA messenger technology, popularly known for its use in the Pfizer-BioNTech and Moderna Covid-19 vaccines, or with chemical compounds.
Izpisua, who created 132 human-monkey embryos in a controversial experiment in China, says the main goal of the upcoming monkey study is to certify whether the rejuvenating treatment is safe in the long term and to understand what molecular changes are produced. For the scientist, it’s important to understand illness “as a process of cell deterioration that is reversible.” Izpisua also points out that low-calorie diets have a positive impact on health, and that it may be possible to develop medicines that “mimic the beneficial effect of calorie restriction.”
Izpisua is optimistic this research will yield results. “I am convinced that within two decades we will have tools that not only treat symptoms, but also can predict, prevent and treat diseases and aging through cellular rejuvenation.” He concludes: “Our end goal is to find new forms of helping everyone to slow or even reverse the processes that lead to disease.” English El País
Thought & Experience
the mystery of how we know what we know
“A new study by researchers at the Medical College of Wisconsin (MCW) untangles the mystery of how we know what we know, uncovering that conceptual knowledge is tied to perceptual and experiential information.
“Our study addresses the question of how our thoughts relate to the physical world that we experience through our senses,” said Dr. Leonardo Fernandino, assistant professor of neurology and biomedical engineering at MCW.
“We worked to find out how much of each type of information, including categorical, word-associative, and sensory information, is encoded in neural representations of word concepts.”
Using functional magnetic resonance imaging (fMRI), Dr. Fernandino and his team measured neural activity throughout the brain while participants read hundreds of different words presented on a screen. Each word produced a unique activation pattern in the participant’s brain.
By analyzing these neural activation patterns, the researchers were able to quantify the extent to which different types of information were used by the brain to represent word meaning. Specifically, they evaluated how much information related to natural categories, word associations, or sensory experience was involved in the brain’s representation of word meaning.
The analysis was based on the degree of similarity between word meanings that should be expected according to each type of information.
“As an example, ‘vodka’ and ‘nitroglycerin’ are very similar according to how they appear to the senses, since both are clear, odorless liquids, but we think of them as belonging to very different categories—drinks and explosives, respectively,” said Dr. Fernandino.
Computer modeling was used to predict the degree of similarity between word meanings according to each type of information, and these predictions were compared to the similarities between the neural activation patterns corresponding to each word meaning.
What we found is that each of these types of information may appear to be encoded in the neural representation of word concepts when examined in isolation; however, when we took into account the way their similarity predictions overlap with each other, our data showed that experiential information was the only type that predicted the similarities between activation patterns independently. The other types of information only predicted the similarities between neural activation patterns to the extent that their predictions matched the predictions of experiential models,” said Dr. Fernandino.
This experimental confirmation that experiences and sensory information are key to conceptual knowledge is groundbreaking for a subject area that has been studied since the fifth century BCE.
“This has been the subject of a long-standing debate in philosophy and psychology that can be traced back to the Ancient Greek philosophers Plato and Aristotle,” said Dr. Fernandino.
Plato argued that humans are born with innate ideas, which are mental templates for all sorts of things we can name or recognize. Aristotle argued that mental categories were not present from birth but were learned from experience.
Today, researchers are still split with respect to these perspectives. Some believe that conceptual categories are represented in the brain in “symbolic” form rather than from learned sensory experiences. As conceptual knowledge is further studied using modern advancements, the research from Dr. Fernandino and the team at MCW is key in providing concrete evidence otherwise.”
The metaverse: where the art is virtual but the headache is real
“Are we in the metaverse right now?” I ask the man in line behind me. We’ve been waiting about 30 minutes to be outfitted with holographic glasses that will make 3D digital images appear in rooms that, to the naked eye, look empty.
Once we have on our glasses, a whimsical forest with falling origami-shaped leaves appears in one room, the skull of Abraham Lincoln in another. A horse neighs down the hall. As we wait, a child twirls around a virtual ballerina as his parent cautions him to look out for the flesh-and-blood humans.
We’re at Verse, an art exhibit where nothing is nailed to the walls and visitors can walk right through the digital images before them. It’s held at the Mint, a stately building in downtown San Francisco. In the 1870s, the Mint was said to have housed nearly one third of the nation’s wealth. The vaults that once held gold are now bare, and the brick-walled space is a backdrop for weddings, haunted houses and tonight’s display of non-fungible tokens, or NFTs.
Peter, who’s waiting patiently in line behind me, says that yes, we’re in a version of the metaverse. He declines to use his full name because he works at Meta, the company formerly known as Facebook, which is working hard to convince the world that this next version of the Internet will be awesome.
The term metaverse was coined 30 years ago by novelist Neal Stephenson, who imagined a science fictional universe where avatars inhabit a virtual world similar to our physical one. Peter’s boss, Meta co-founder and chief executive Mark Zuckerberg, calls the metaverse “an embodied Internet where you’re in an experience, not just looking at it. Like walking through an exhibit of 3D art, going to virtual concerts or conferences. In the metaverse, paper money is replaced by cryptocurrency, which you need to buy the art dancing before your eyes at the Mint. Each NFT costs between $25 and $250,000, though they’re priced in various cryptocurrencies.
An NFT of NSA whistleblower Edward Snowden sold for more than $5 million last year.
But wandering through the Mint, Sari Stenfors is skeptical.
Everyone is talking about the metaverse, Stenfors said, “but not so many people are actually visiting it.” A self-described “futurist” from Berkeley, Calif., she stands in front of a television screen that projects fiery wings off her back. Stenfors thinks she resembles a heavenly creature or something from hell — she’s not sure which. “I keep feeling like I’m at Burning Man, but I want to touch and interact more,” Stenfors said. “Touch is needed. I’m sure it’s going to come. Smells. We’re going to get it all.”
Later she straps on a HoloLens2 — a bulky $3,500 pair of glasses from Microsoft — and tries not to bump into anyone. Being transported to another world is uncomfortable. For my maiden voyage, the HoloLens is screwed on too tight and leaves a mark on my forehead that’s visible hours later.
Before a Verse attendant sends me to explore on my own, she asks whether I can see the ballerina pirouetting down the hallway. When I reach my hand out in front of me, its shape is rendered in multicolored polygons, twisting as I turn my hand this way and that. Instead of a traditional art exhibit with plaques on the walls, at Verse, attendees point the cursor in their HoloLens toward a square icon to reveal who made the NFT, its price and a little about the artist’s intention in creating it. This is about commerce, after all.
Sure, it’s cool to be immersed in a forest or walk past glowing lotus flowers, but navigating it is difficult. The glasses call for precise movements, and most Verse attendees are still learning. I aim my HoloLens at a specific icon, and if I move my head just a smidge, the display vanishes. There’s so much to absorb that it’s easy to forget to blink or feel nauseated.
A banner in LED lights beckons attendees to ponder “What Is Real?” as they wander from one hologram to the next, potentially missing a huge artifact in plain sight: A stamp mill from the late 1800s, used to pulverize quartz so that gold could be extracted. Advanced technology for its time that’s now obsolete. At one point, I reach out and touch an empty brick wall to remind myself that the physical world exists not just as a container or a backdrop. Tiny grains of brick dust fall to the floor.
Wandering through Verse reminds me of the thrill and disorientation that came with the early days of smartphones. Accessing email while out and about instead of seated at a desktop at home, looking up maps while en route from point A to point B, sharing pictures of your lunch on social media before you’d taken a single bite, or Googling facts about an old building as you were sitting on its steps. That was the information overload circa 2007.
The newer version on display at the Mint is even more dizzying. It’s like having a million tabs open in your brain and walking right through them splayed out in front of you.
Learning to use a HoloLens is akin to learning to use a mouse and cursor for the first time, explained Ray Kallmeyer, the start-up founder behind Verse. “We find usually, after 30 to 60 minutes, that people are pretty solid with it,” Kallmeyer said.
“Hop off, because I think you being on my shoulders is messing with my vision,” 32-year-old Aaron Jones said to his daughter, Kaelyn, 6. He gently deposits her on the ground, where she spins alongside the ballerina and paws at the other creatures surrounding her. The dragon is Kaelyn’s favorite; “I think it’s majestic,” she said, before telling the creature to “get out of my face!”
Jones and Kaelyn have played around with virtual reality before, he said, but before they set foot in the Mint, Jones introduced a new concept: art. “I was trying to explain to her that art can be money and can be traded,” Jones recalled.
Summer Lindman, a 32-year-old marketer in San Francisco, showed up at Verse armed with the cryptocurrency Ethereum she bought about six years ago, when it was $11 a coin. (It was hovering around $2,500 early this week.) She had never seen an NFT in the real world and was curious. One artist’s work caught her eye — “that looks like real art,” she said of an animated illustration of a reclining woman taking a selfie. But she wasn’t convinced.
“In covid, we’ve constantly been on screens, and I’m craving more of a physical experience,” Lindman said. Though her journey through the metaverse did involve leaving the house, she still felt disconnected from those around her. “Would I want to go to a gallery to see a bunch of NFTs in the future?” Lindman asked herself. She’s not so sure.
A 32-year-old San Franciscan who works in art and design, has traveled to the metaverse before, when the HoloLens was in a rudimentary state. Though the technology has evolved, and her walk through Verse is “pretty vivid,” she still feels like she’s wearing a shield and heading off to battle. People go to galleries for people-to-people interactions, Yang noted, and wearing heavy glasses adds “an additional layer of friction between humans and the art.”
“As an artist, I’m not convinced this is the route,” Yang said. “Most people thriving in this community, they’re investors, not artists.”
Are the images on display at Verse art, money or both? Kallmeyer freely admits that some NFTs are not aesthetically pleasing. “I don’t think anyone is looking to put a Bored Ape in their bedroom,” Kallmeyer said. Owning a Bored Ape NFT, which can set you back $235,000 to $2.8 million, is more about the status that comes with it (like being part of a virtual country club, Kallmeyer said) than the visual appeal. Kallmeyer likens the popular BAYC to the Dutch tulip mania of the 1630s. Eventually the bubble will burst.
The NFT enthusiast at the Mint will essentially be taking home the rights to a one-of-a-kind piece of digital art. Verse has sold almost $40,000 in NFTs since opening in early February, Kallmeyer said, with 300 of the exhibit’s buyers making their first NFT purchase. Since each piece is unique, it can be bought and sold like a collectible.
For some potential buyers, the fact that NFTs can only be displayed digitally (on a phone, on the Web or viewed through a virtual-reality device) causes them to pause. “I don’t know if I’d want this,” said Jorelle Jones, 40, “it’s not the same as my art on the wall.” Jones likens his night in the metaverse to the experience of playing Atari as a child in the 1980s versus what it’s like to play video games now. He’s waiting for the technology to advance. “It’s cool now,” Jones said, “but it’ll be cooler in 50 years.”
Kallmeyer sees the metaverse as the evolution of the Internet. And yes, he created an NFT, called “Nature,” to depict that progression: A chrome-colored man, hunched over and lumbering on all fours like a primate. He considers the work, which sells for 1.5 Ethereum or around $4,000, as a comment on humanity’s role on Earth. “Are we part of nature or separate?” Kallmeyer asked. “If a human makes a building, a hologram or the Internet, are those part of nature too? I would say yes. Most of our lives are enabled by the parts of us that are in the cloud.”
Stenfors, the futurist, would like to see the metaverse used to facilitate more personal connection. Maybe her activity tracker would notify friends that she’d only had five hours of sleep, so they’d know why she’s cranky while sitting down to coffee together, without her having to say so. “We could share a lot more than in real life,” Stenfors said.
But do we want to render the question “How are you?” obsolete?
Being in this altered state is taxing, even for digital natives like 6-year-old Kaelyn. Before her 30 minutes with the HoloLens is up, Kaelyn pronounces herself done. “I have a bigggg headache,” she said.
Her dad removes her glasses. For the young girl, the dragons and ballerinas are out of sight, though still spinning, breathing and up for sale for those of us wandering through the metaverse with cryptocurrency to burn.” MSN, WP
That Organic Cotton T-Shirt Is Not as Organic as You Think
According to those who source, process and grow the cotton in India, much of that is fake.
“This product contains independently certified organic cotton grown without chemical pesticides, chemical fertilizers and genetically modified seeds,” the product description reads.
With the fashion industry trumpeting its sustainability commitments, those labels are both a means of value signaling and a lure to consumers willing to pay more to act better.
There’s only one problem: Much of the “organic cotton” that makes it to store shelves may not actually be organic at all.
The largest single producer of the world’s organic cotton supply is India, which accounts for half of the organic cotton sold globally, and where the organic cotton movement appears to be booming. According to Textile Exchange, a leading organic proponent, organic cotton production in India alone grew 48 percent in the last year, despite the pandemic.
However, much of this growth is fake, say Indians who source, process and grow organic cotton.
At the heart of the problem is an opaque certification system rife with opportunities for fraud. Consumers are assured of “organic” material by brands, which rely on official stamps of approval from external organizations. Those in turn rely on reports from opaque local inspection agencies that base their conclusions on a single planned yearly inspection (in the case of the facilities) or a few random visits (for farms).
In recent months, the credibility of these inspection agencies has been destroyed. In November, the European Union voted to no longer accept Indian organic exports certified by the main companies responsible for organic cotton: Control Union, EcoCert and OneCert. And in January, the international agency that provides accreditation to organic inspection agencies, IOAS, withdrew OneCert’s ability to inspect and certify cotton processors for these labels.
The firm that helps brands source organic cotton, has spent the past year hunting down organic cotton with his team only to see suppliers disappear when they start asking for proof of authenticity. He estimates between one half and four-fifths of what is being sold as organic cotton from India is not genuine. And almost the entire supply chain is implicated in what he calls a game of “smoke and mirrors.”
For at least a decade, in reports and at conferences convened by agitated large brands and the network of nongovernmental organizations that serve them, the organic cotton industry in India has been described as in “crisis,” but the problems have been kept largely out of the public eye.
Pesticides, Chemical Fertilizer and Genetically Modified Seeds
In Khargone district in India’s central state of Madhya Pradesh, one of the country’s largest producers of certified organic cotton, farmers have cultivated the plant known locally as white gold for generations.
In the late 1990s, when cotton grown without chemical pesticides or synthetic fertilizer was a rarefied product purchased exclusively by high-priced yoga and wellness brands, two Swiss companies formed the bioRe Foundation to support organic cotton growing in Madhya Pradesh.
Through India’s contract production system, which allows cotton suppliers to register up to 500 farmers as a single corporate entity, bioRe started sourcing and selling organic cotton regulated by India’s Agricultural and Processed Food Products Export Development Authority.
What the farmers did not know, however, was that growing without pesticides and fossil-fuel fertilizer produces on average 28 percent lower yields than conventional cotton farming; that organic cotton seeds produce lower quality, shorter fibers; and that increasingly brands were using their market power to negotiate the price of organic cotton down to the same price as conventional cotton or even cheaper because of its lower quality.
Aashish Joshi, who oversees bioRe’s organic cotton project in India, acknowledged that the premiums customers were paying for organic cotton rarely reached legitimate organic cotton farmers. “I would say that people are benefiting,” he said, “but these are who are indulging in fraudulent cotton.”
According to yearly reports on the state of the industry by Textile Exchange, an American organization founded in 2002 to promote sustainability, organic cotton production in India has more than doubled in the last four years: to 124,000 metric tons in 2021 from 60,000 metric tons in 2017. Yet based on the limited quantities of organic seed in circulation, industry insiders say the amount of organic cotton on the market today is impossible.
“Seeds are not available,” said Mr. Joshi of bioRe.
Arun Ambatipudi, executive director of Chetna Organic, one of a few nonprofits that provides training and support to organic cotton farmers in India, said, “It led to a lot of cheating.”
The two main links in the long supply chain between farmers and shoppers are Western organizations that provide organic cotton labels, and local inspection offices.
But neither GOTS nor Textile Exchange performs inspections themselves. Instead, they use the local offices of international inspection businesses, including OneCert, EcoCert and the behemoth Control Union, which certifies more than 100 programs in 70 countries, to verify claims.
These businesses — which are paid by the very ginners, spinners and farmers they are supposed to be policing — visit farms, test seeds for G.M.O. contamination, and once a year inspect and verify the facilities that process, spin, weave, dye and sew the garments. They then produce a paper certificate, which is sent to GOTS and Textile Exchange, who pass on the paper to clothing manufacturers, who pass it on to brands.
Selling conventional cotton as organic, they change a paper transaction certificate to match the larger volume. Inspectors visit once a year only to verify that a facility is capable of following protocol for keeping organic cotton separate — they do not inspect all the cotton moving through. Furthermore, there is no central database to look up the transaction numbers to make sure a certificate hasn’t already been used. In this way, the volume of certified organic cotton doubles, triples or even quadruples as it moves up through the supply chain.
In 2009, India’s agricultural export agency discovered wide scale fraud in the country’s cotton belt, with entire villages certifying genetically modified cotton as organic.
U.K. Vats, the government official who oversees scope certificates for India’s organic cotton industry, did not respond to multiple interview requests.
In November, the European Union started rejecting Indian organic exports certified by five companies — including Control Union, EcoCert and OneCert — after shipments of sesame were found to contain a carcinogenic substance. Chastened by the U.S. and E.U. actions, the Indian government also fined the companies and barred them from registering new processors or exporters.
This problem is not confined to India, experts say; questions have been raised about organic cotton from China and Turkey, which account for another quarter of the global supply. And the organization that audits and certifies the certifiers, IOAS, withdrew OneCert’s ability to inspect and approve cotton-processing facilities globally in January.”
Divorcing Couples Fight Over the Kids, the House and Now the Crypto
Dividing the family’s Bitcoin stash has become a major source of contention in divorce cases.
“The divorce dragged on for eight years, almost as long as the marriage. The wealthy San Francisco couple sparred over child support, the profits from the sale of the husband’s software company and the fate of their $3.6 million home.
But the most consequential court battle between Erica and Francis deSouza concerned a bitter dispute over millions of dollars in missing Bitcoin.
Mr. deSouza, a tech executive, had bought a little over 1,000 Bitcoins before he separated from his wife in 2013, and then lost nearly half the funds when a prominent cryptocurrency exchange collapsed. After three years of litigation, a San Francisco appeals court ruled in 2020 that Mr. deSouza had failed to properly disclose some elements of his cryptocurrency investments, which had exploded in value. The court ordered him to give Ms. deSouza more than $6 million of his remaining Bitcoin.
In legal circles, the deSouzas’ case has become known as perhaps the first major Bitcoin divorce. Such marital disputes are increasingly common. As cryptocurrencies gain wider acceptance, the division of the family stash has turned into a major source of contention, with estranged couples trading accusations of deception and financial mismanagement. An ugly divorce tends to generate arguments about virtually everything. But the difficulty of tracking and valuing cryptocurrency, a digital asset traded on a decentralized network, is creating new headaches. In many cases, divorce lawyers said, spouses underreport their holdings, or try to hide funds in online wallets that can be difficult to get into.
“Originally, it was under the mattress, and then it was the bank account in the Caymans,” said Jacqueline Newman, a divorce lawyer in New York who works with high-net-worth clients. “Now it’s crypto.”The rise of cryptocurrencies has provided a useful medium of exchange for criminals, creating new opportunities for fraud. But digital assets are not untraceable. Transactions are recorded on public ledgers called blockchains, enabling savvy analysts to follow the money.
Some divorce lawyers have come to rely on a growing industry of forensic investigators, who charge tens of thousands of dollars to track the movement of cryptocurrencies like Bitcoin and Ether from online exchanges to digital wallets. The investigative firm CipherBlade has worked on about 100 crypto-related divorces over the last few years, said Paul Sibenik, a forensic analyst for the company. In multiple cases, he said, he has traced more than $10 million in cryptocurrency that a husband hid from his wife.
In interviews, nearly a dozen lawyers and forensic investigators described divorce cases in which a spouse — usually the husband — was accused of lying about cryptocurrency transactions or hiding digital assets. None of the couples agreed to be interviewed. But some of the divorces have created paper trails that shed light on how these disputes unfold.
The deSouzas married in September 2001. That same year, Mr. deSouza founded an instant-messaging company, IMlogic, that he eventually sold in a deal netting him more than $10 million, according to court records.
Mr. deSouza’s cryptocurrency investments date to April 2013, when he spent time in Los Angeles with an early crypto entrepreneur, who pitched him on digital assets. That month, Mr. deSouza bought about $150,000 of Bitcoin.
The deSouzas separated later that year, and Mr. deSouza soon disclosed that he owned the Bitcoin. By the time the couple were ready to divide their assets in 2017, the value of that investment had ballooned to more than $21 million.
But there was a catch. That December, Mr. deSouza revealed that he had left a little under half the funds in a cryptocurrency exchange that went bankrupt in 2014, putting the money out of reach.
In court filings, Ms. deSouza’s lawyers said it was “egregious” that her husband had failed to mention earlier that so much of the Bitcoin was gone, and argued that his secretive management of the investment had cost the couple millions of dollars. The lawyers also speculated that Mr. deSouza might be hoarding additional funds.
No secret stash ever materialized. A spokeswoman for Mr. deSouza said he had disclosed the entirety of his cryptocurrency holdings at the beginning of the divorce. “As soon as Francis knew that the Bitcoin was caught up in the Mt. Gox bankruptcy, he told his ex-wife,” the spokeswoman said. “Had the Mt. Gox bankruptcy not occurred, the division of the BTC would have been entirely uncontroversial.”
Ms. deSouza declined to comment through her lawyer.
But the appeals court found that Mr. deSouza, 51, who is now the chief executive of the biotech company Illumina, had violated rules of the divorce process by failing to keep his wife fully apprised of his cryptocurrency investments.
He was ordered to give Ms. deSouza about half the total number of Bitcoins he had owned before the Mt. Gox bankruptcy, leaving him with 57 Bitcoins, worth roughly $2.5 million at today’s prices. Ms. deSouza’s Bitcoins are now worth more than $23 million.
Not all crypto divorces involve such large sums. A few years ago, Nick Himonidis, a forensic investigator in New York, worked on a divorce case in which a woman accused her husband of underreporting his cryptocurrency holdings. With the court’s authorization, Mr. Himonidis showed up at the husband’s house and searched his laptop. He found a digital wallet, which contained roughly $700,000 of the cryptocurrency Monero.
“He was like: ‘Oh, that wallet? I didn’t think I even had that,’” Mr. Himonidis recalled. “I was like, ‘Seriously, dude?’”
In another case, Mr. Himonidis said, he discovered that a husband had moved $2 million in cryptocurrency out of his account on the platform where people buy, sell and store digital currencies. A week after his wife filed for divorce, the man transferred the funds to digital wallets, and then left the United States.
A court can order a cryptocurrency exchange to turn over funds. But the online wallets in which many investors store cryptocurrency are not subject to any centralized control; access requires a unique password created by the wallet’s owner. Without that digital key, the husband’s funds were effectively out of the soon-to-be-ex-wife’s reach.An exchange can still be a valuable source of information. In 2020, Gregory Salant, a divorce lawyer in White Plains, N.Y., worked with a client who believed her husband owned cryptocurrency he hadn’t disclosed. Mr. Salant sent a subpoena to Coinbase, which responded with a spreadsheet that he found impossible to understand. He hired a forensic investigator, Mark DiMichael, to translate the spreadsheet and track down the assets.
The husband had also transferred nearly $225,000 in cryptocurrency to other anonymous addresses. A review of his tax returns showed he hadn’t reported spending the cryptocurrency or converting it into dollars.
“Plaintiff either neglected to report the sale or sending of the Missing Cryptocurrency on his income tax returns,” the report concluded, “or Plaintiff still retained control of the Missing Cryptocurrency.”
The case was eventually settled. Under the final agreement, some of the husband’s other assets were allocated to the wife to resolve the cryptocurrency dispute.
“It was a package deal,” Mr. Salant said. “‘I won’t touch your retirement account, you won’t touch my retirement account, we give a $25,000 swing for the crypto.’
In some divorces, the cryptocurrency stash turns out to be tiny or even nonexistent. Several lawyers described cases in which a wife’s suspicions were unfounded. But over and over, said Kelly Burris, a divorce lawyer in Austin, Texas, who primarily represents husbands, men have come into her office and detailed their plans to hide cryptocurrency.
Ms. Burris is a fixture on the divorce industry lecture circuit, where she talks about the challenges of tracking digital assets. In some cases, she said, her male clients have proposed slightly more sophisticated frauds, like using a crypto A.T.M. to buy Bitcoin with cash.
“They’re thinking, ‘There’s no way she can track it,’” Ms. Burris said. “‘There’s no way she can get access.’”
The Sky Is Amazing Because Anyone Can Enjoy It
Amazing, simple, pure and touching description:
the diary of a nine year old, Rohan, describing sky
“The sky. You might think it is useless and just there, however it is one of the most fascinating sights ever! When I wake up, I eagerly scramble out of my comfy bed, leap towards my window and yank open my curtains just to get a view of the scenic sky.
The morning sun comes up and the ripple-like clouds (called cirrocumulus) make the sky look like an upside down, pink river. When I walk to school, the neon-yellow sun grows brighter in the baby-blue sky. At this time, the sky produces high, wispy clouds (called cirrus) and big fluffy ones (called cumulus) that embrace the winter sky around them. At our lunch break, our faces light up when the snow starts to fall. We leap in the air trying to catch some. I love it when light grey clouds envelope the sky and give it a tranquil effect.
At home when it gets to dinner time, I gaze at the sky outside and observe that it has become a soothing coal-black, and it does not change until I fall asleep. The beauty of the sky is: wherever you go, you see it differently, but it always looks nice. The sky is something that keeps us alive and allows us to experience amazing sights however rich or poor we are, so we ought to be grateful for it.”
$315 billion in market value has been erased from these 4 companies since Apple’s iOS privacy changes went into effect last year
“A slew of earnings reports from social media companies on Wednesday revealed the extent of damage related to Apple’s iOS privacy changes made last year.
In April 2021, Apple updated its iOS so that users have to opt-in to allowing ad- tracking by social media apps like Facebook and Twitter, rather than the prior practice of having to opt-out. Apple essentially unburied the opt-out feature from deep in its setting menu and instead made it pop up to the front of the screen whenever a user first opens an app that relies on advertising.
This change is estimated to cost Meta Platforms an estimated $10 billion in revenue this year, CFO David Wehner said in its earnings call, as it makes it harder for the company to deliver targeted advertisements to its users. “Like others in our industry, we faced headwinds as a result of Apple iOS changes. Apple created 2 challenges for advertisers: one is that the accuracy of our ads targeting decreased, which increased the cost of driving outcomes; the other is that measuring those outcomes became more difficult,” Meta Platform chief operating officer Sheryl Sandberg said in its earnings call.
And Meta Platforms expects the headwind stemming from Apple’s IDFA privacy change to “moderately increase” throughout 2022, Sandberg said.
“We believe management’s tone around iOS impact has deteriorated, and what was once described as ‘manageable’ now appears to be a $10B revenue headwind in 2022,” JPMorgan said in a Thursday note.
The earnings results from social media companies on Wednesday highlighted the weakness to investors, resulting in a steep sell off in their stocks. In Thursday trades, Meta Platforms fell 22%, Snap fell 18%, Twitter fell 8%, and Pinterest fell 11%.
Since Apple’s privacy update went into effect in late April 2021, these four social media companies have erased a combined $315 billion in market value at their Thursday intraday lows.
Market value April 26, 2021: $861 billion
Market value today: $656 billion
Market value lost: $205 billion
Market value April 26, 2021: $92 billion
Market value today: $41 billion
Market value lost: $51 billion
Market value April 26, 2021: $53 billion
Market value today: $27 billion
Market value lost: $26 billion
Market value April 26, 2021: $49 billion
Market value today: $16 billion
Market value lost: $33 billion.
How to Remain Youthful and Resilient Despite Stress
“Stress can be a precursor to other mental health disorders including depression and anxiety, as well as a factor for premature aging. Researchers discuss stress management techniques that can build resilience to stressors and could help protect against the impact stress has on the aging process.
A bit of stress can be good for your mental and physical wellbeing, but too much can lead to anxiety, depression and other health problems. It can also make you age faster. So learning to become more stress-resilient is important if you’re not in a hurry to grow old fast.
Studies have shown that people who aren’t good at managing their stress can increase their risk of dying prematurely by 43%. The increase in deaths might in part be due to the effect stress has on DNA.
DNA, which is found in nearly every cell (except red blood cells), contains genes that code for the building blocks (proteins) that comprise your body. DNA consists of two strands woven together in the famous “double helix”. Your cells are constantly making copies of themselves, and when a cell divides, the two strands unravel and an identical copy is made of each – well, most of the time.
Sometimes mistakes happen during the replication process, especially at the end of DNA strands. These mistakes can cause mutations in the copied DNA, leading to the cell becoming cancerous. Luckily, cells have protective caps called telomeres at the ends of the DNA strand that are designed to ensure these mistakes don’t happen.
Telomere caps are like sequences of beads (telomeric repeats). Each time the cell divides, the next generation loses one bead of telomeric repeats. Unfortunately, each cell has a fixed number of these repeats, meaning that it can only replicate a certain number of times before the protective telomere caps are eroded. This number of cell divisions is called the Hayflick limit. Once a cell reaches the Hayflick limit (up to 60 cell divisions, for most cells), it self-destructs (safely). This is the essence of ageing.
Some cells in the body, especially the immune cells that fight infection, possess molecules called telomerase. Telomerase can add the beads back (telomeric repeats) in immune cells (and some others, such as cancerous cells), meaning that ageing can be reversed in these cells. Telomerase can add the beads back, meaning that ageing can be reversed in the cells in question.
This makes sense as immune cells have to replicate many times to fight viruses and bacteria. Without telomerase, they would reach their Hayflick limit and disappear, leaving organisms with no protection. Unfortunately, however, even telomerase stops working properly when people reach their 80s and lose their immune cells to ageing.
It’s not all beyond your control
Smoking, excess alcohol consumption, being overweight and stress are all associated with telomere loss. Telomerase does not work as efficiently when a person suffers from excessive stress, and this causes premature aging.
Adopting a healthy lifestyle, such as eating both plant-based and meat, can stop and even reverse the process. And physical activity, especially intense exercise, can also increase telomerase activity. So leading a healthy life can decrease the speed of aging as can managing your stress.
As we mentioned earlier, not all stress is bad. In psychology, we differentiate between “eustress” (positive stress), which is necessary for us to succeed at work, in sport and relationships, and “distress” (negative stress), when pressure becomes too much for us to manage. Distress is what most of us mean when we say or feel that we are stressed; it is also what might speed up aging in your cells.
Embracing stressful events and using coping strategies or becoming resourceful when dealing with challenges, can create stress resilience, which in turn is associated with longer telomeres.“
The pandemic had changed every aspect of society
‘It’s All Just Wild’: Tech Start-Ups Reach a New Peak of Froth
There’s more money and more bubbly behavior. Investors insist it’s rational.
“How crazy is the money sloshing around in start-up land right now?
It’s so crazy that more than 900 tech start-ups are each worth more than $1 billion. In 2015, 80 seemed like a lot.
It’s so crazy that hot start-ups no longer have to pitch investors for money. The investors are the ones pitching them.
It’s so crazy that founders can start raising money on a Friday afternoon and have a deal closed by Sunday night.
It’s so crazy that even sports metaphors fall short.
It’s not like one jump ball — it’s 10,000 jump balls at once,” said Roy Bahat, an investor with Bloomberg Beta, the start-up investment arm of Bloomberg. “You don’t even know which way to look, it’s all just wild.” He now carves out two hours a day for whatever “emergency deal of the day” pops up.
The funding frenzy follows nearly two years of a pandemic when people and businesses increasingly relied on tech, creating bottomless opportunities for start-ups to exploit. It follows breakthroughs in artificial intelligence, nuclear technology, electric vehicles, space travel and other areas that investors say are poised to change the world. And it follows nearly a decade in which tech companies have dominated the stock market.
The activity has crossed into even frothier territory in recent months, as tech start-ups offering food delivery, remote-work software and telehealth services realized that they not only would survive the pandemic but were in higher demand than ever. The money hit a fever pitch in the final months of 2021 as investors chased a limited pool of start-ups and as tech stocks like Apple, which topped a valuation of $3 trillion, reached new heights.
The result is a booming ecosystem of highly valued, cash-rich start-ups in Silicon Valley and beyond that are expanding at breakneck speed and trying to unseat stalwart companies in all kinds of fields. Few in the industry see a limit to the growth.
The pot of gold at the end of the rainbow has become bigger than ever,” said Mike Ghaffary, an investor at Canvas Ventures. “You can invest in a company that could one day be a trillion-dollar company.”
Astonishing data for 2021 tell the story. U.S. start-ups raised $330 billion, nearly double 2020’s record haul of $167 billion, according to PitchBook, which tracks private financing. More tech start-ups crossed the $1 billion valuation threshold than in the previous five years combined. The median amount of money raised for very young start-ups taking on their first major round of funding grew 30 percent, according to Crunchbase. And the value of start-up exits — a sale or public offering — spiked to $774 billion, nearly tripling the prior year’s returns, according to PitchBook.
The big-money headlines have carried into this year. Over a few days this month, three private start-ups hit eye-popping valuations: Miro, a digital whiteboard company, was valued at $17.75 billion; Checkout.com, a payments company, was valued at $40 billion; and OpenSea, a 90-person start-up that lets people buy and sell nonfungible tokens, known as NFTs, was valued at $13.3 billion.
Investors announced big hauls, too. Andreessen Horowitz, a venture capital firm, said it had raised $9 billion in new funds. Khosla Ventures and Kleiner Perkins, two other venture firms, each raised nearly $2 billion.
The good times have been so good that warnings of a pullback inevitably bubble up. Rising interest rates, expected later this year, and uncertainty over the Omicron variant of the coronavirus have deflated tech stock prices. Shares of start-ups that went public through special purpose acquisition vehicles last year have slumped. One of the first start-up initial public offerings expected this year was postponed by Justworks, a provider of human resources software, which cited market conditions. The price of Bitcoin has sunk nearly 40 percent since its peak in November.
But start-up investors said that had not yet affected funding for private companies. “I don’t know if I’ve ever seen a more competitive market,” said Ambar Bhattacharyya, an investor at Maverick Ventures.
Even if things slow down momentarily, investors said, the big picture looks the same. Past moments of outrageous deal making — from Facebook’s acquisitions of Instagram and WhatsApp to the soaring private market valuations of start-ups like Uber and WeWork — have prompted heated debates about a tech bubble for the last decade. Each time, Mr. Bahat said, he thought the frenzy would eventually return to normal.
Instead, he said, “every single time it’s become the new normal.”
Investors and founders have adopted a seize-the-day mentality, believing the pandemic created a once-in-a-lifetime opportunity to shake things up. Phil Libin, an entrepreneur and investor, said the pandemic had changed every aspect of society so much that start-ups were accomplishing five years of progress in one year.
The basic fabric of the world is up for grabs,” he said, calling this time “the changiest the world has ever been.” In mid-2020, he started Mmhmm, a video communication provider for remote workers, and has landed $136 million in funding. Mr. Libin said he heard from interested investors a few times a week.
The less frothy times, young, fast-growing tech companies sought new investment every 18 months. Now they are re-upping multiple times a year.
For Daniel Perez, a co-founder of Hinge Health, a provider of online physical therapy programs, the unsolicited emails from investors started in late 2020. They contained pitch decks packed with the elaborate research that the investment firms had done on Hinge, including interviews with dozens of its customers and data on its competitors.
These reverse pitches,” which numbered in the 20s, were meant to persuade Mr. Perez to take money from the investment firms. He also got several term sheets, or investment contracts, from investors he had never met before.
“Often when we’re speaking to investors, they’d cut me off and say, ‘Let me show you what I already know about you,’” Mr. Perez said. The reverse pitch from Tiger Global, the firm that Hinge picked to help lead a $300 million funding round alongside the investment firm Coatue Management last January, was 90 pages.
A few months after Hinge announced that funding, the reverse pitches started rolling in again. Three different investors sent Mr. Perez videos from celebrities they had hired on Cameo to make their case. One was from Andrei Kirilenko, a former Utah Jazz player whom Mr. Perez was a fan of.
“It was a constant drumbeat that got a bit more feverish,” Ms. Perez said. In October, Hinge raised another $600 million led by Coatue and Tiger.
Bhattacharyya said this kind of “pre-work” had become table stakes for firms looking to land a hot investment. The goal is to pre-empt the company’s formal fund-raising process and show how excited the firm is about the start-up, while possibly sharing some useful data.
“It’s part of the selling process,” he said.
Vijay Tella, founder of Workato, an automation software start-up in Mountain View, Calif., said the dossiers sent by prospective investors during his company’s latest round of funding in November were so elaborate that one firm had interviewed 30 of Workato’s customers. Afterward, Mr. Tella worried that his customers had been spammed by prospective investors and even apologized to some.
Workato, which raised $310 million across two rounds of funding last year and is valued at $5.7 billion, is not currently seeking more money. But, Mr. Tella said, “I would bet right now that those calls are still happening.” NY Times
Be Careful Of What You Eat
Switch to a certified organic diet to build a strong immune system
France bans dozens of glyphosate weedkillers
“France’s health and environment agency said on Monday it was banning dozens of glyphosate-based weedkillers, most of the volume of such products sold in France, ruling there was insufficient data to exclude health risks.
The ANSES agency was withdrawing the marketing licence for 36 products which would no longer be authorised for use after the end of next year, it said in a statement.
The products accounted for nearly three-quarters of the volume of glyphosate products sold last year in France, the European Union’s biggest agricultural producer, it said.
Applications to launch four new glyphosate-based products had also been rejected, ANSES added.
Glyphosate, first developed by Bayer’s Monsanto unit under the brand Roundup, has been a focus of controversy since a World Health Organisation agency concluded in 2015 that it probably causes cancer. Bayer denies the charge.
Bayer is facing potentially costly lawsuits in the United States and politicians in the European Union have been debating outright bans of the weedkiller.
Austria, which is attempting to be the first European country to ban all uses of the weedkiller, said on Monday a law on the ban cannot go into force on Jan. 1 as planned because the European Commission was not properly notified.
The list of products to be withdrawn included several versions of Roundup along with certain other Bayer-owned products, plus other brands sold by around a dozen other manufacturers.
Glyphosate is off-patent and marketed worldwide by a large number of other crop chemical groups in addition to Bayer.
It was about 5 and a half years ago that Dr. Stephanie Seneff heard a talk from Professor Don Huber, who is over 80 years old and still active, giving lectures all around the world about glyphosate.
The Truth About Glyphosate
Dr. Seneff, a MIT scientist, believes that chemical companies do an excellent job of deflecting. They usually blamed something else. Diving into what glyphosate is, she says it can mess up the protein in the kidneys that preserve the water used to concentrate the urine.
So, when you’re in the high heat and sweating, you lose water. You need to be able to retain water as much as you can. And the critical proteins involved with retaining water is compromised by glyphosate. There are many other proteins as well but bottom line, the kidneys are affected.”
The studies have shown that glyphosate goes into the testes, causes damage and leads to cancers. It also disrupts the cells that protect the sperm. The cells get calcium overload, and they’re exposed to glyphosate.
The research papers have shown that glyphosate paralyzes the gut. Other studies have also shown that health conditions like obesity and depression are linked to glyphosate. Even serotonin deficiency is related to this harmful chemical; corn, soy, and canola oil are sugar-based. No wonder sugar is bad for you because it’s covered in glyphosate.”
She adds, “Then they started to get roundup resistance. Weeds were showing up. So they had to use more glyphosate each year to kill these weeds. Which is why the usage went up exponentially.”
At this point, it reached a crisis point. There were very resistant weeds. There wasn’t enough glyphosate on weeds enough to kill it. So, companies started introducing dual products containing glyphosate and 2,4-D, which is a component of Agent Orange.
Be Careful Of What You Eat
Dr. Seneff says it’s quite feasible to switch to a 100% certified organic diet. Companies are spraying so much glyphosate on wheat, which is why we have an epidemic of gluten intolerance.
“Because the wheat is sprayed right before the harvest, it goes into the wheat germ which is the healthiest part of the wheat. It’s the part that has the highest part of glyphosate contamination. Wheat bread is going to be highly contaminated. Levels are also high on samples of legumes, chickpeas, lentils, hummus, and garbanzos from Canada and the U.S.”
On the other hand, Europe has much lower levels of glyphosate. She also believes that some of the crops that are sprayed before the harvest end up with a higher concentration of glyphosate in the food products, as well as the ones that are GMO roundup ready.
When you eat foods that are contaminated with glyphosate, you usually don’t get like a bellyache or a headache that’s very obvious. When you are exposed to it, most of it works its way through your body unchanged and goes out through urine or feces. But there’s a small percentage of it—1 or 2%, that goes into the tissues.
First and foremost, she recommends eating organic foods. We must also be wary of our environments like golf courses and even schoolyards because a lot of chemicals are used to maintain the grassy areas. Another way to adopt a healthier lifestyle is educating people not to choose glyphosate, especially when killing weeds.
There are natural ways to kill weeds like vinegar and salt or pulling by hand. Dandelions are protective against glyphosate. Herbs are important to keep the gut healthy. Consuming sulfur-containing foods like seafood, garlic, and onion is good. Eating preventive foods, whole foods and probiotics help. It’s also healthy to get out in sunlight.”
France24 & Health Journal
Lifelong Learning and Knowledge Can Decrease Aging of the Brain
“Older adults with an academic background showed lower increases of signs of brain degeneration than those who were less educated, a new study reports.
The benefits of meaningful education and lifelong learning extend into old age. The initial findings of a long-term study show that certain degenerative processes are reduced in the brains of academics. Their brains are better able to compensate for age-related cognitive and neural limitations.
A good education is an excellent way to embark on a successful career and develop your personality. But can education also have a positive effect on our brains as we get older? A team of researchers under the University Research Priority Program “Dynamics of Healthy Aging” led by Lutz Jäncke, professor of neuropsychology at the University of Zurich, has now explored this question in a long-term study.
The researchers followed more than 200 senior citizens for over seven years. The study participants are not affected by dementia, have average to above-average intelligence and lead highly active social lives. They were examined neuroanatomically as well as neuropsychologically using magnetic resonance imaging at regular intervals.
Based on complex statistical analyses, the researchers were able to show that academic education had a positive effect on age-related brain degeneration.
In her Ph.D. thesis, first author Isabel Hotz used novel automatic methods among others to study so-called lacunes and white matter hyperintensities. These degenerative processes showed up as “black holes” and “white spots” on the digital images.
The reasons for this are not yet known and may have to do with small, unnoticed cerebral infarcts, reduced blood flow or loss of nerve pathways or neurons. This can limit a person’s cognitive performance, in particular when degeneration affects key regions of the brain.
The findings revealed that over the course of seven years, senior citizens with an academic background showed a significantly lower increase in these typical signs of brain degeneration. “In addition, academics also processed information faster and more accurately—for example, when matching letters, numbers of patterns. The decline in their mental processing performance was lower overall,” summarizes Hotz.”
Researchers find plastic in “clean air” in the mountains
Particles are able to travel long distances and reach the highest altitudes.
Micro-plastics from Africa and North America found airborne in French Pyrenees, 2,877 metres above sea level
“From Mount Everest to the Mariana Trench, microplastics are everywhere – even high in the Earth’s troposphere where wind speeds allow them to travel vast distances, a new study has found.
Microplastics are tiny fragments – measuring less than 5mm – that come from packaging, clothing, vehicles and other sources and have been detected on land, in water and in the air.
Scientists from the French national research institute CNRS sampled air 2,877 metres above sea level at the Pic du Midi Observatory in the French Pyrenees, a so-called “clean station” because of the limited influence exerted on it by the local climate and environment.
There they tested 10,000 cubic metres of air a week between June and October of 2017 and found all samples contained microplastics.
Using weather data, they calculated the trajectories of different air masses preceding each sample and discovered sources as far away as north Africa and North America.
The study’s main author, Steve Allen of Dalhousie University in Canada, told AFP that the particles were able to travel such distances because they were able to reach great altitudes.
“Once it hits the troposphere, it’s like a superfast highway,” he said.
The research also points to microplastic sources in the Mediterranean Sea and the Atlantic Ocean.
“The marine source is the most interesting,” Allen said.
“Plastic leaving the ocean into the air that high – it shows there is no eventual sink for this plastic. It’s just moving around and around in an indefinite cycle.”
While the amounts of microplastics in the samples at the Pic du Midi do not pose a health risk, the study’s co-author Deonie Allen notes that the particles are small enough for humans to breathe in.
And she says their presence in a zone thought to be protected and far from pollution sources should give pause.
“It questions the relationship we have with plastic,” she said, adding that the problem was global.
Allen said that it also showed that disposing of plastic by shipping it abroad was a flawed strategy.
“It’s going to come back to you,” she said.”