Daily Archives: May 4, 2021

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NEW YORK, New York, LEIDEN, Netherlands & CAMBRIDGE, Mass., May 04, 2021 (GLOBE NEWSWIRE) -- RTW Investments, LP (RTW), a global, full life-cycle investment firm that focuses on identifying transformational and disruptive innovations across the biopharmaceutical and medical technologies sectors, and ProQR Therapeutics N.V. (Nasdaq: PRQR) (ProQR), a company dedicated to changing lives through the creation of transformative RNA therapies for genetic eye diseases, today announced that Yarrow Biotechnology, Inc. (Yarrow) , a company newly created by RTW, has in-licensed exclusive rights to ProQRs antisense oligonucleotide technology (ASO) to develop and commercialize potential therapies for an undisclosed non-ophthalmic target. Yarrow is focused on developing ASO-based therapeutics for disorders with high unmet need.

Roderick Wong, MD, Managing Partner and Chief Investment Officer of RTW, said: We believe RNA-based therapies hold great promise to treat genetically-defined diseases. We are excited to partner with ProQR to in-license the first target to be developed in Yarrows pipeline.

Under the terms of the agreement, ProQR is eligible to receive up to $115 million of upfront and milestone payments, plus single digit percentage royalties on the net sales of any resulting products during the royalty term. ProQR will also have the right to receive an undisclosed percentage of equity in the form of shares of common stock of Yarrow. ProQR will be responsible for certain preclinical activities with reimbursement for the research costs by Yarrow, while Yarrow will be responsible for continuing development of the program and commercialization activities.

Gerard Platenburg, Chief Innovation Officer at ProQR, will join Yarrows board of directors.

Peter Fong, PhD, Head of Company Creation at RTW, said: Our partnership with ProQR fits perfectly into Yarrows mission to develop first-in-class ASO-based therapies for genetically-defined diseases. We look forward to a long and productive partnership.

Daniel A. De Boer, Founder and CEO of ProQR, said: As we focus ProQR on our core genetic eye disease strategy, we are pleased to partner with Yarrow to advance our technology in applications outside the eye, while generating value from this partnership and the broad applicability of our platform.

About RTW Investments, LP

RTW Investments, LP (RTW) is a New York-based, global, full life-cycle investment firm that focuses on identifying transformational and disruptive innovations across the biopharmaceutical and medical technologies sectors. As a leading partner of industry and academia, RTW combines deep scientific expertise with a solution-oriented investment approach to support emerging medical therapies and the companies and academics developing them.

About Yarrow Biotechnology, Inc.

Yarrow Biotechnology, Inc. (Yarrow) is a newly formed biotechnology company developing antisense oligonucleotide-based therapeutics for disorders with high unmet need. Yarrow has established a proprietary target discovery engine leveraging large-scale human genetics studies to uncover novel targets where there is a significant unmet need.

Yarrow is the latest new company created and backed by RTW Investments, LP.

About ProQR

ProQR Therapeutics is dedicated to changing lives through the creation of transformative RNA therapies for the treatment of severe genetic rare diseases such as Leber congenital amaurosis 10, Usher syndrome and retinitis pigmentosa. Based on our unique proprietary RNA repair platform technologies we are growing our pipeline with patients and loved ones in mind. Learn more about ProQR at http://www.proqr.com.

Forward Looking Statements for ProQR

This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as "anticipate," "believe," "could," "estimate," "expect," "goal," "intend," "look forward to", "may," "plan," "potential," "predict," "project," "should," "will," "would" and similar expressions. Such forward-looking statements include, but are not limited to, statements regarding the collaboration with RTW and Yarrow and the intended benefits thereof, including milestone and royalty payments from commercial product sales, if any, from the products covered by the collaboration and the issuance of equity in Yarrow to ProQR, as well as the potential of our technologies and product candidates. Forward-looking statements are based on management's beliefs and assumptions and on information available to management only as of the date of this press release. Our actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, the risks, uncertainties and other factors in our filings made with the Securities and Exchange Commission, including certain sections of our annual report filed on Form 20-F. These risks and uncertainties include, among others, the cost, timing and results of preclinical studies and clinical trials and other development activities by us and our collaborative partners whose operations and activities may be slowed or halted by the COVID-19 pandemic; the likelihood of our clinical programs being executed on timelines provided and reliance on our contract research organizations and predictability of timely enrollment of subjects and patients to advance our clinical trials and maintain their own operations; our reliance on contract manufacturers to supply materials for research and development and the risk of supply interruption from a contract manufacturer; the potential for future data to alter initial and preliminary results of early-stage clinical trials; the unpredictability of the duration and results of the regulatory review of applications or clearances that are necessary to initiate and continue to advance and progress our clinical programs; the ability to secure, maintain and realize the intended benefits of collaborations with partners; the possible impairment of, inability to obtain, and costs to obtain intellectual property rights; possible safety or efficacy concerns that could emerge as new data are generated in research and development; and general business, operational, financial and accounting risks, and risks related to litigation and disputes with third parties. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, even if new information becomes available in the future, except as required by law.

For ProQR Therapeutics N.V.

Investor Contact:Sarah KielyProQR Therapeutics N.V.T: +1 617 599 6228skiely@proqr.comorHans VitzthumLifeSci AdvisorsT: +1 617 430 7578hans@lifesciadvisors.com

Media Contact:Cherilyn Cecchini, MDLifeSci CommunicationsT: +1 646 876 5196ccecchini@lifesciadvisors.com

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ProQR Therapeutics and Yarrow Biotechnology, an RTW Investments, LP Incubated Company, Announce Exclusive Worldwide License and Discovery...

HHMI Investigator Erich Jarvis and dozens of colleagues have launched an ambitious project to read the genomes of every vertebrate species. Credit: Peter Ross

Its one of the most audacious projects in biology today reading the entire genome of every bird, mammal, lizard, fish, and all other creatures with backbones.

And now comes the first major payoff from the Vertebrate Genomes Project (VGP): near complete, high-quality genomes of 25 species, Howard Hughes Medical Institute (HHMI) Investigator Erich Jarvis with scores of coauthors report April 28, 2021, in the journal Nature. These species include the greater horseshoe bat, the Canada lynx, the platypus, and the kkp parrot one of the first high-quality genomes of an endangered vertebrate species.

The paper also lays out the technical advances that let scientists achieve a new level of accuracy and completeness and paves the way for decoding the genomes of the roughly 70,000 vertebrate species living today, says HHMI Investigator and study coauthor David Haussler, a computational geneticist at the University of California, Santa Cruz (UCSC). We will get a spectacular picture of how nature actually filled out all the ecosystems with this unbelievably diverse array of animals.

Together with a slew of accompanying papers, the work is beginning to deliver on that promise. The project team has discovered previously unknown chromosomes in the zebra finch genome, for example, and a surprise finding about genetic differences between marmoset and human brains. The new research also offers hope for saving the kkp and the endangered vaquita dolphin from extinction.

These 25 genomes represent a key milestone, explains Jarvis, VGP chair and a neurogeneticist at The Rockefeller University. We are learning a lot more than we expected, he says. The work is a proof of principle for whats to come.

The VGP milestone has been years in the making. The projects origins date back to the late-2000s, when Haussler, geneticist Stephen OBrien, and Oliver Ryder, director of conservation genetics at the San Diego Zoo, figured it was time to think big.

Instead of sequencing just a few species, such as humans and model organisms like fruit flies, why not read the complete genomes of ten thousand animals in a bold Genome 10K effort? At the time, though, the price tag was hundreds of millions of dollars, and the plan never really got off the ground. Everyone knew it was a great idea, but nobody wanted to pay for it, recalls HHMI Investigator and HHMI Professor Beth Shapiro, an evolutionary biologist at UCSC and a coauthor of the Nature paper.

Plus, scientists early efforts at spelling out, or sequencing, all the DNA letters in an animals genome were riddled with errors. In the original approach used to complete the first rough human genome in 2003, scientists chopped up DNA into short pieces a few hundred letters long and read those letters. Then came the fiendishly difficult job of assembling the fragments in the right order. The methods werent up to task, resulting in misassemblies, major gaps, and other mistakes. Often it wasnt even possible to map genes to individual chromosomes.

The introduction of new sequencing technologies with shorter reads helped make the idea of reading thousands of genomes possible.These rapidly developing technologies slashed costs but also reduced quality in genome assembly structure. Then in 2015, Haussler and colleagues brought in Jarvis, a pioneer in deciphering the intricate neural circuits that let birds trill new tunes after listening to others songs. Jarvis had already shown a knack for managing big, complex efforts. In 2014, he and more than a hundred colleagues sequenced the genomes of 48 bird species, which turned up new genes involved in vocal learning. David and others asked me to take on leadership of the Genome 10K project, Jarvis recalls. They felt I had the personality for it. Or, as Shapiro puts it: Erich is a very pushy leader, in a nice way. What he wants to happen, he will make happen.

Jarvis expanded and rebranded the Genome 10K idea to include all vertebrate genomes. He also helped launch a new sequencing center at Rockefeller that, together with one at the Max Planck Institute in Germany led by former HHMI Janelia Research Campus Group Leader Gene Myers, and another at the Sanger Institute in the UK led by Richard Durbin and Mark Blaxter, is currently producing most of the VGP genome data. He asked Adam Phillippy, a leading genome expert at the National Human Genome Research Institute (NHGRI), to chair the VGP assembly team. Then, he found about 60 top scientists willing to use their own grant money to pay for the sequencing costs at the centers to tackle the genomes they were most interested in. The team also negotiated with the Mori in New Zealand and officials in Mexico to get kkp and vaquita samples in a beautiful example of international collaboration, says Sadye Paez, program director of the VGP at Rockefeller.

The massive team of researchers pulled off a series of technological advances. The new sequencing machines let them read DNA chunks 10,000 or more letters long, instead of just a few hundred. The researchers also devised clever methods for assembling those segments into individual chromosomes. They have been able to tease out which genes were inherited from the mother and the father. This solves a particularly thorny problem known as false duplication, where scientists mistakenly label maternal and paternal copies of the same gene as two separate sister genes.

I think this work opens a set of really important doors, since the technical aspects of assembly have been the bottleneck for sequencing genomes in the past, says Jenny Tung, a geneticist at Duke University, who was not directly involved with the research. Having high-quality sequencing data will transform the types of question that people can ask, she says.

The teams improved accuracy shows that previous genome sequences are seriously incomplete. In the zebra finch, for example, the team found eight new chromosomes and about 900 genes that had been thought to be missing. Previously unknown chromosomes popped up in the platypus as well, as members of the team reported online in Nature earlier this year. The researchers also plowed through, and correctly assembled, long stretches of repetitive DNA, much of which contain just two of the four genetic letters. Some scientists considered these stretches to be non-functional junk or dark matter. Wrong. Many of the repeats occur in regions of the genome that code for proteins, says Jarvis, suggesting that the DNA plays a surprisingly crucial role in turning genes on or off.

Thats just the start of what the Nature paper envisions as a new era of discovery across the life sciences. With every new genome sequence, Jarvis and his collaborators uncover new and often unexpected findings. Jarviss lab, for example, has finally nabbed the regulatory region of a key gene parrots and songbirds need to learn tunes; next, his team will try to figure out how it works. The marmoset genome yielded several surprises. While marmoset and human brain genes are largely conserved, the marmoset has several genes for human pathogenic amino acids. That highlights the need to consider genomic context when developing animal models, the team reports in a companion paper in Nature. And in findings published last year in Nature, a group led by Professor Emma Teeling at University College Dublin in Ireland discovered that some bats have lost immunity-related genes, which could help explain their ability to tolerate viruses like SARS-CoV-2, which causes COVID-19.

The new information also may boost efforts to save rare species. It is a critically important moral duty to help species that are going extinct, Jarvis says. Thats why the team collected samples from a kkp named Jane, part of a captive breeding program that has brought the parrot back from the brink of extinction. In a paper published in the new journal Cell Genomics, of the Cell family of journals, Nicolas Dussex at the University of Otago and colleagues described their studies of Janes genes along with other individuals. The work revealed that the last surviving kkp population, isolated on an island off New Zealand for the last 10,000 years, has somehow purged deleterious mutations, despite the species low genetic diversity. A similar finding was seen for the vaquita, with an estimated 10-20 individuals left on the planet, in a study published in Molecular Ecology Resources, led by Phil Morin at the National Oceanic and Atmospheric Administration Fisheries in La Jolla, California. That means there is hope for conserving the species, Jarvis concludes.

The VGP is now focused on sequencing even more species. The project teams next goal is finishing 260 genomes, representing all vertebrate orders, and then snaring enough funding to tackle thousands more, representing all families. That work wont be easy, and it will inevitably bring new technical and logistical challenges, Tung says. Once hundreds or even thousands of animals readily found in zoos or labs have been sequenced, scientists may face ethical hurdles obtaining samples from other species, especially when the animals are rare or endangered.

But with the new paper, the path ahead looks clearer than it has in years. The VGP model is even inspiring other large sequencing efforts, including the Earth Biogenome Project, which aims to decode the genomes of all eukaryotic species within 10 years. Perhaps for the first time, it seems possible to realize the dream that Haussler and many others share of reading every letter of every organisms genome. Darwin saw the enormous diversity of life on Earth as endless forms most beautiful, Haussler observes. Now, we have an incredible opportunity to see how those forms came about.

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Citation

Arang Rhie et al. Towards complete and error-free genome assemblies of all vertebrate species. Nature. Published online April 28, 2021. doi: 10.1038/s41586-021-03451-0

Excerpt from:
Project to Read Genomes of All 70000 Vertebrate Species Reports First Discoveries - Howard Hughes Medical Institute

For more than 30years, scientists have followed a rule they imposed on themselves to avoid growing a human embryo in a lab dish for more than 14 days.

Until recently, the "14-day rule" was largely academic. Scientists couldn't grow themfor that long if they wanted to.

But in 2016, two teams of researchers reached 12days, and in 2019, another group grew monkey embryos for 19 days.

These advances have spurredsome scientists to argue in two recent papersthat the 14-day rule should bemodified or dropped. There's a lot to be learned by pushing embryos out to 28 days, they say.

The regulatory committee of theInternational Society for Stem Cell Research, which lays down guidelines for the scientificfield,has been debating the issuefor months and is expected to issue its final decision this month.

Some ethicists and scientistsare concerned that revising the rule just asit becomes technologically feasible to break it is ridiculous and morally repugnant.

"If you abandoned every rule or law that inhibits you as soon as it inhibits you, we'd live in a lawless world," said Ben Hurlbut, a historian of science at Arizona State University.

And somepeople consider human embryo researchto be unethical at any stage.

"Whether 14 days, 14 months, or anywhere in between, such 'rules'remain contrivances to justify the most unethical kinds of science and to allow for the exploitation of our own vulnerable human offspring," said Tadeusz Pacholczyk, a neuroscientist and director of education at the National Catholic Bioethics Center in Philadelphia.

A single cell is removed from a human embryo to be used in generating embryonic stem cells for scientific research.Advanced Cell Technology via AP

Countries are free to ignore rules set by the society, but scientists for decades have generally abided by them. (In the U.S., there's no national law about the 14-day rule, though some states have their own regulations.)

Some cultures and religions believe that human life begins at conception, or that the human embryo carries a special status from conception onward. Other cultures believe that life starts later in fetal development, or even at birth.

Biologists routinely grow amphibian and mammal embryos in petri dishes, but human embryos are different.

Until about 14 days after conception, the human embryo looks likean undifferentiated blob of cells, which is one of the reasons the two week timeframemade sense, several scientists said.

Robin Lovell-Badge, who sits on the International Stem Cell Society committee that's considering overturning the rule, said scientists will take any changes seriously.

"We've stuck with that rule for over 30 years," he said.

Lovell-Badgefavors extending the limit, as long as the research is scientifically justified and has public support.

Not everyone in the scientific community shares this position.

"It's been a difficult part of the guidelines to get agreement on," Lovell-Badge said. "You have very wide-ranging views."

Some scientists argue there's a lot to be learned by pushing the 14-day rule out another two weeks.

Right now the second two weeks after fertilization is considered a "black box" because so little is known about it, said Insoo Hyun, a professor of bioethics atCase Western and Harvard universities. Heco-wrote a March 5 opinion piece arguing for a careful, stepwiseextension of the 14-day rule.

"You have to really make your case for it,"Hyun said."You have to explain what you want to do and why, have a very clear picture of where the next stopping point is."

Women generally don't know they're pregnant before 28 days, so historically, there has not been tissue from aborted or miscarried fetuses available for research.

The central nervous system, heart and other organs begin to develop during this crucial two-week period. The body plan is established. Cells that will become eggs and sperm start to form. Aspects of theplacenta are set up.

In many ways,days 14 through28 are the most interesting period of human development, Lovell-Badge said. "You can do a whole lot of incredibly valuable research," in that timeframe, he said.

And it's in that window that many things can go wrong in a pregnancy, such as miscarriage or abnormalities.

Perhaps there are treatments that could be developed to fix these problems, if they are better understood,Hyunsaid, just as pregnant women now take vitamin supplements to prevent spina bifida, in which the spine doesn't developproperly.

Do you think scientists should be allowed to grow embryos in a dish beyond 14 days? Share this story.

Developing embryos for another week "will thus illuminate this poorly understood period of our development and bring greater understanding of pregnancy loss and developmental disease,"saidMagdalenaZernicka-Goetz,theBritish scientist who developed the technique for growing human embryos for nearly two weeks.Zernicka-Goetz,author of a 2020 book on human development called "The Dance of Life,"would like to extend the 14-day rule out one week to 21 days.

"This will enable thescientiststo study a period of development that are highly susceptible to developmental failure, something that happens quite frequently in human pregnancy," she wrote in an email, stressing work should be closely regulated"to achieve these potential biomedical advances within an appropriate bi-ethical framework."

Despite their differences, most scientists seem to agreethere's no reason to push development past 28 days.

By onemonth after conception, embryonic tissue is easier to obtain and study and theorgans have formed, leaving fewer questions to answer.

"You wouldn't need to take them much beyond that point anyway," Lovell-Badgesaid.

Pacholczyk, of the Catholic Bioethics Center, said there's simply no justification for 14 days or any other time limit.

"Researchers have been feigning for a long time that the 14-day rule was somehow an ethical tenet grounded in biological facts while in reality it has been little more than a ceremonial 'line in the sand' and it should come as little surprise that they are now seeking to move that line beyond 14 days," he wrote in an email.

Even some who strongly supportscientific research are uncomfortable extending the 14-day rule.

HenryGreely, who directs the Stanford Center for Law and the Biosciences at Stanford University in California, saidthere should be a hard-stop endpointfor embryo research.

"Even though I do not personally give strong moral status to embryos, the idea of doing research on 18-day-oldhuman embryos is disturbing," said Greely, author of the new book "CRISPR People: The Science and Ethics of Editing Humans."

This sequence of images shows the development of embryos after correcting for a genetic error that would otherwise cause a type of inherited heart disease.OHSU

"I'd like to see an endpoint that had some rationale that would make it likely to stick," he said.

Growing an embryo in a lab dish instead of a woman's womb is necessarily different, Greely said, and may not represent a "real" embryo anyway.

"Does a 14-day embryo that is not implanted deep in a woman's uterus tell us anything meaningful about a 14-day embryo that is?" he asked.

Marcy Darnovsky, executive director of the Center for Genetics and Society, a nonprofit advocacy group,said efforts to overturn the 14-day rule are another example of scientific over-reach.

"There's a real problem with scientists who are jumping ahead of the public," she said.

Scientists should not be the ones who get to decide where society's moral boundaries lie,she and Hurlbut said.

"If moves are made to usurp these questions from wider society," Hurlbut said, "it's to the detriment of democracy and to the detriment of sciencecertainly in the long run, and probably in the short run."

Contact Karen Weintraub at kweintraub@usatoday.

Health and patient safety coverage at USA TODAY is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Healthcare. The Masimo Foundation does not provide editorial input.

Published10:13 am UTC May. 2, 2021Updated10:13 am UTC May. 2, 2021

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Should scientists be allowed to grow human embryos in a dish beyond 14 days? Is it scientifically important or morally wrong? - USA TODAY

ALISO VIEJO, Calif.--(BUSINESS WIRE)--The international rare disease patient advocacy organization, Global Genes, is pleased to announce the 6th Annual RARE Drug Development Symposium (RDDS) in partnership with the Orphan Disease Center of the University of Pennsylvania. The June 9-11 virtual event will connect and educate hundreds of advocates, clinicians, and academic and industry researchers to explore the latest science, opportunities, and challenges to the advancement of therapies for more than 7,000 rare diseases.

New to this year's event is an optional preconference workshop targeted to attendees who are in the earlier stages of their research efforts or careers and looking to build knowledge in core competencies that will be expanded upon in the main RDDS program. The main program will address the current landscape of rare drug development and allow attendees to interact with subject matter experts and other rare disease stakeholders to help them better understand and develop their impact and role in advancing potential treatments.

This year, the RDDS keynote speaker will be David Fajgenbaum, M.D., MBA, MSc, co-founder and executive director of the Castleman Disease Collaborative Network (CDCN), assistant professor of medicine in Translational Medicine & Human Genetics at the University of Pennsylvania, associate director, Patient Impact for the Orphan Disease Center of the University of Pennsylvania, and author of the national bestselling book, Chasing My Cure: A Doctors Race to Turn Hope Into Action.

Dr. Fajgenbaum has been a leader in helping researchers to prioritize treatments for COVID-19 clinical trials and inform patient care through the CORONA (COvid19 Registry of Off-label & New Agents) Project. Were thrilled to have him share his insights during this critical time in health care and understand how we can apply these approaches to accelerate progress in rare disease research and treatments, said Craig Martin, CEO at Global Genes. The rare disease leaders who will be featured during the RDDS have tremendous depth of knowledge to share, and we look forward to sharing it with members of the rare community during this event.

RDDS will continue to host the CureAccelerator Live! For Rare Diseases 2021 event on June 10 in partnership with Cures Within Reach, a not-for-profit organization exclusively dedicated to using the speed, safety, and cost-effectiveness of already approved drugs, devices, diagnostics, nutraceuticals, and combination products to impact patients with unmet medical needs driving more treatments to more patients more quickly.

The emergence of therapeutic platforms creates unprecedented opportunities for treatments to improve the lives of those living with rare diseases, said Jim Wilson, M.D., Ph.D., director, Gene Therapy Program, and Rose H. Weiss, professor and director at the Orphan Disease Center of the University of Pennsylvania. We are delighted to collaborate with Global Genes to educate the rare disease community on research directed to these treatments.

Thank you to our gold sponsors, Horizon Therapeutics and Greenwich Biosciences, and silver sponsor, Pfizer, Inc., for their generous support of this important event.

For more information, visit http://www.globalgenes.org/rdds.

About Global Genes

Global Genes is a 501(c)(3) nonprofit organization dedicated to eliminating the burdens and challenges of rare diseases for patients and families globally. In pursuit of our mission, we connect, empower, and inspire the rare disease community to stand up, stand out, and become more effective on their own behalf helping to spur innovation, meet essential needs, build capacity and knowledge, and drive progress within and across rare diseases. We serve the more than 400 million people around the globe and nearly one in 10 Americans affected by rare diseases. If you or someone you love has a rare disease or are searching for a diagnosis, contact Global Genes at 949-248-RARE, or visit our resource hub.

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Global Genes and Orphan Disease Center of the University of Pennsylvania to Convene Patient Group Leaders, Researchers, Clinicians and Industry for...

The title of a puzzling opinion piece published recently in the New York Times, written by author Markham Heid, asks: Can we learn to live with germs again? The subtitle proceeds to answer the curious question by suggesting that our health depends on resuming our pre-pandemic lifestyles that expose us to bacteria, despite the risks posed by the coronavirus. In short, the entire article promotes, in a virulent form of the not-so-subtle and unscientific construct, the cure cant be worse than the disease, taken to its extreme and bizarre conclusions that good hygiene is worse than COVID-19.

The author of this piece, Markham Heid, who the Times describes as a longtime health and science journalist who has written extensively about the microbiome, is, in fact, no such expert. He received his bachelors degree from the University of Michigan in English (2005), and his masters in journalism from Northwestern University (2009). He is a freelance writer, a title that in this case signifies that he writes about many things about which he does not know very much.

In his LinkedIn profile, he wrote, Im a regular contributor at TIME, Medium, and Food & Wine. My work has appeared in Playboy, Popular Mechanics, Everyday Health, Sports Illustrated, and elsewhere. Ive received reporting awards from the Society of Professional Journalists and the Maryland, Delaware, and D.C. Press Association. Im always open to new opportunities.

Armed with these dubious credentials, Heid sets outwith the endorsement of the New York Timesto mislead and miseducate his readers.

After introducing a video commissioned by United Airlines that demonstrates how breakthrough technology was being employed to clean air cabins, Heid questions these drastic measures. He claims that a century of accumulated scientific understanding of germs and disease has led to the misconception that only sterile environments are safe ones. The deception lies entirely with Mr. Heid and the Times in their attempt to pawn off their pseudo-scientific rationale. In short, they are attempting to assert that the measures employed to mitigate community transmission are doing more harm than good.

The article, which received a significant showing in the Times, provocatively opens with disgusting glossy close-up photos of filthy fingernails caressing the brow of a child with reddened eyes, a grime-ridden door handle clasped with dirty hands, and another showing snot dripping into a childs saliva-soaked open mouth whose face is covered with crayon markings.

Later in the piece, another photo shows macaroni and cheese splattered onto a childs hands and sleeves. And still another, a near-empty bottle of milk clasped with filthy hands, presumably being drunk directly out of the container.

Aside from their shock value, the images are intended to browbeat the reader into accepting the conclusions that these unhygienic practices are essential for enhancing our immunity and well-being. Exposure to these friendly pathogens, the article asserts, is vital to boost the immune system appropriately, and our obsession with cleanliness and sterility, avoidance of hugging and kissing each other during the pandemic could hazardously impact our bodies microbiomes and subsequent health.

Heid goes on to add, Despite the now consensus recognition that air transmission, not surface spread, is more important, most pandemic sanitation practices have continued. We continue to annihilate every microbe in our midst, even though most are harmless. After citing New York Citys efforts to keep subways clean, as well as surveys that indicate commuters were appreciative of these measures, he added, But some health experts are watching this ongoing onslaught with a mounting sense of dread. They fear that many of the measures weve employed to stop the virus, even some that are helpful and necessary, may pose a threat to human health in the long run if they continue.

Heid then enters the discussion in the barely understood world of human microbiomes, the microscopic environments of our guts, skin and oral membranes, where trillions of bacteria live in a symbiotic relationship with all living animals, including humans. Allusions are then made to recent associations between the changes in a persons microbiome and diseases such as asthma or obesity to defend this stance.

It is understood that some diseases of gynecologic (bacterial vaginosis) or gastrointestinal (Clostridium difficile colitis) origin have been linked to bacterial overgrowth. It has also become clear that misuse of antibiotics can promote the development of antibiotic-resistant strains of bacteria. Some researchers have hypothesized that there may be correlations between the development of early-onset autoimmune diseases and the dominance of certain bacteria in the gut microbiome. However, these assertions have far from been established. Heids equating these diseases to hygienic practices and the field of microbiomes is an attempt to mislead.

In a 2018 article published in Nature Medicine, Dr. Jack Gilbert and colleagues, after reviewing the current understanding of the human microbiome, conclude, There remains much that we do not understand about human microbiomes. The sources of bacteria that colonize an infant include the mother and other caregivers (even one-day-old pre-term infants have unique microbiomes that differ from each other and from the mother but possibly derived from their mothers), and human genetics shapes microbiome-immune interaction.

They added, The human microbiome is highly personalized. Understanding the relevance of the differing microbiota between individuals is confounded by the uniqueness of an individuals microbiome. The microbiome of every individual is unique to the person, making a generalization about their impact on the promotion of disease difficult.

Indeed, the study of human microbiomes is fascinating and novel, and over time may provide important insight into the dynamics of human diseases and health. However, as the authors note, present investigations have failed to establish firm conclusions and instead only raise critical questions. Many of these studies have been broad-based observational studies or animal models that lack sufficient context to justify shifts in public health practices.

However, with regards to the COVID-19 pandemic, which has, in a short period, infected over 150 million people worldwide, killing, at a minimum, 3.2 million people, how does the concern raised over the impact of hygienic standards and the impact of the microbiome even compare to the scale of this global crisis? This is a preposterous and dangerous insinuation on the part of Mr. Heid and the Times.

He attempts to defend this position by citing a paper published in the Proceedings of the National Academy of Sciences (PNAS) in January, titled, The hygiene hypothesis, the COVID pandemic, and consequences for the humane microbiome. What becomes immediately clear upon reading the PNAS paper is that the position being forwarded by Heid and the Times is incongruent with the subject of the article he cites.

In no uncertain terms, the authors wrote, We want to be clear: Preventing COVID-19 transmission is necessary, and the hygienic transformations of the past 100 years have resulted in major reductions in mortality from infectious diseases. Their foray into the world of microbiomes and COVID-19 is posed as a question: What microbial functions might we lose as a result of COVID-19 prevention efforts? What are the consequences as humans continue to encounter nutritional and immune challenges in future generations, and what can be done to mitigate them? They respond to their query, This pandemic presents a significant opportunity to study, in real-time, the relationship between an infectious agent, the microbiome, precipitous and uneven social and economic changes, and their combined effects on health and disease.

The hygiene hypothesis, first put forth by Dr. David Strachan in the late 1980s, states that early childhood exposure to various microorganisms, specifically from the gut flora and parasites, possibly aid in bolstering a young persons immune system. More precisely, the lack of exposure is thought to lead to a deficiency in immune tolerance, which predisposes environmental allergies.

However, this hypothesis has been erroneously interpreted as an attack on personal cleanliness, although there is no indication that any excesses on that score have impacted allergies and immune disorders and they have not been known to increase the risks of infections. On the contrary, hygienic standards have been critical for protecting vulnerable populations and have been the first line of defense in preventing the spread of antibiotic-resistant organisms and emerging infectious diseases such as COVID-19.

The authors of the PNAS article explained that the loss of microbial diversity, which has accelerated over the last century, is a byproduct of increased urbanization, overuse of antibiotics, and other medications. Additionally, they cite changes in birth and infant feeding practices, intensified hygienic practices, and the reduced diversity of global diet, specifically the decreased intake of dietary fiber and increased consumption of processed foods, to the development of disease. Compounding these have been the widespread use of tobacco, alcohol and other drugs.

They theorized that the decline in these essential healthy microbes, a result of a shift in the globalization of food manufacturing to higher caloric and cheaper sources, has led to the rise in rates of chronic diseases such as obesity, diabetes, asthma and autoimmune disease. They write, This process of microbial diversity loss is occurring unevenly across the planet. Clean water, soap, and sanitation are not equally distributed to all people; access to and use of antibiotics is widespread in low- and middle-income countries, constituting a quick fix infrastructure, even for the poorest population. Moreover, multiple vulnerable populationsurban residents, racial and ethnic minorities, migrants, low-income earnersdisproportionately suffer from certain chronic diseases linked to altered microbial functionality.

Though they acknowledge up front that there is little direct evidence of interactions between human microbiomes and COVID-19 disease, the fundamental purpose of their perspective was to recognize the observations that susceptibility to the SARS-CoV-2 is linked to biological determinants that are impacted by demographic and socioeconomic factors that render the elderly, racial and ethnic minorities, and those with lower socioeconomic status more likely to suffer worse outcomes from COVID-19 infection; these same groups have existing pathologies that correlate with dysbiosis [imbalance between the types of organisms present in a persons natural microflora] of gut microbiota.

The concerns raised by the PNAS article are far more urgent than those being discussed by Heids article, which is entirely out of touch with the lives of millions of people whose lives and livelihoods have been upended by the economic upheaval and health ramifications created by the COVID-19 pandemic.

It is worth noting that the coupling of hand washing to disease prevention is only a recent observation in the annals of medical history. In 1848, a Hungarian doctor, Ignaz Semmelweis, while working at a Viennese hospital, observed that the high maternal deaths they were encountering were a byproduct of a potential pathogen acquired when training physicians were called away during cadaver dissections to deliver an expecting mother without washing their hands. At the time, there was no clear understanding of bacterial or viral infections.

To test his hypothesis, he ordered physicians to wash their hands and instruments in a chlorine solution. After implementing a hand hygiene protocol, there was a dramatic decline in maternal mortality from 18 to 1 percent. However, Dr. Semmelweis met with resistance from his colleagues, offended by the notion that they were the source of the maternal infections. Dr. Nancy Tomes, a professor of history at Stony Brook University, New York, explained, The majority of doctors in Vienna at this time were from middle- or upper-class families, and they thought of themselves as very clean people compared with the working-class poor. He was insulting them when he said their hands could be dirty.

Dr. Semmelweis would lose his position and eventually was committed to a psychiatric institution, where he died at 47. Still, the following decades proved to be decisive in the field of infectious disease. Louise Pasteur brought awareness to pathogens and how to kill them using heat. Joseph Lister, a British surgeon, introduced antiseptic surgery, which included hand washing, which, Tomes noted, moved from being something doctors did to something everybody had been told to do. Potentially, a breakthrough in the study of microbiomes can provide critical links between social determinants of health and disease. These discoveries in the 19th century were crucial to the advancement of medicine and public health disciplines.

Despite our appreciation of the relationship between unsanitary conditions and disease, these basics in maintaining community hygienic practices are impossible for most countries. According to the World Health Organization and UNICEFs Joint Monitoring Program for Water Supply, Sanitation, and Hygiene, over 60 percent of the worlds population, or 4.5 billion people, lack access to safe sanitation. One in three people on the planet cannot receive safe drinking water. Two billion people use water sources that have been contaminated with feces.

In 2007, the readers of the British Medical Journal voted sanitation as the most important medical milestone since 1840. Ten percent of the global burden of disease is associated with poor sanitation conditions. These predominate in the densely populated urban centers of Africa, Asia and Latin America. Diarrheal disease caused by fecal-oral contamination kills 1.6 million to 2.5 million each year, many under the age of five years, living in developing countries. Adequate sanitation, well-maintained sewage systems and water treatment plants can dramatically reduce the burden of such diseases.

The Times article is an exercise in obfuscation and deceit. Heid deliberately attempts to equate the problem created by issues such as excessive use of antibiotics with hygienic measures essential to stop the spread of COVID-19. To imply that cleaning subways, washing hands, etc., will deprive humans of necessary contact with microbes (such as those we have in our gut) is absurd. One might just as well make the same argument about sanitizing hospitals. But as is well known, the transmission of bacteria and other germs is among the most significant problems confronting doctors and their patients in health facilities.

Heids commentary is aimed at delegitimizing hygienic measures whose implementation might subtract from the corporate bottom line. This is a variant of the dont let the cure be worse than the disease.

Moreover, the article completely ignores the fact that lack of adequate sanitation is, on a global scale, very possibly the greatest threat to health.

If the ignorant Heid is taken seriously, the conclusion to be drawn from his unappetizing piece is: Whenever you enter an office or store, make a point of licking the doorknobs.

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New pandemic advice from the New York Times: Practicing good hygiene may be worse than COVID-19 - WSWS

In inflammatory bowel disease (IBD), inflammation of the digestive tract can cause abdominal pain, diarrhea, fatigue, and weight loss, among other symptoms.

Crohns disease and ulcerative colitis are the two main types of IBD.

The Centers for Disease Control and Prevention (CDC) estimates that around 3 million adults in the United States have IBD.

One of the characteristics of the disease is increased permeability of the walls of the intestine sometimes known as a leaky gut which can provoke inflammation of the gut lining.

Protein complexes called tight junctions (TJs) act similarly to rivets to bind together adjacent cells in the guts lining to prevent microorganisms and other contents from seeping out.

The intestines TJ barrier is defective in IBD and other inflammatory conditions of the gut, including celiac disease and necrotizing enterocolitis.

Currently, there are no effective treatments to tighten the TJ barrier and reduce the permeability of the gut.

However, several studies have found that friendly bacteria in the gut help strengthen the intestinal barrier.

Scientists know that people with IBD have an imbalance in their gut bacteria, with reduced overall diversity of species and larger numbers of bacteria that provoke inflammation.

Researchers have tried to identify particular species of probiotic bacteria that enhance the TJ barrier and that could make effective treatments for IBD, but with inconclusive results.

However, in a new study, scientists have discovered a strain of Lactobacillus acidophilus that strengthens the TJ barrier in human cell cultures.

The strain, known as LA1, also reduced colitis, or inflammation of the inner lining of the colon, in a mouse model of IBD.

Our data indicate that LA1 is able to prevent colonic inflammation formation and promote colitis healing, says lead investigator Dr. Thomas Ma, Ph.D., of Penn State College of Medicine, Hershey Medical Center, in Hershey.

He says the findings suggest that the strain could have applications in a wide range of disorders involving chronic inflammation associated with a leaky gut, in addition to IBD.

These conditions include celiac disease, an autoimmune reaction to gluten in food, and necrotizing enterocolitis, where bacteria invade the intestine wall of premature infants.

The results of the study appear in The American Journal of Pathology.

The researchers screened more than 20 different probiotic species for their ability to tighten the TJ barrier.

They tested the bacteria in cultures of a human cell line called Caco-2, which scientists often use to model the intestinal epithelium.

Only LA1 caused a rapid, strong tightening of the TJ barrier.

The bacteria appeared to achieve this by activating a protein in the membrane of the cells, called a Toll-like receptor.

Toll-like receptors, part of the bodys immune defenses, recognize patterns on the surface of microbes.

Similar to ringing an intruder alarm, when the bacterium bound to the receptors, it triggered a train of events inside the cells that tightened the TJ barrier.

To test whether LA1 would have the same effect in a live animal, the researchers administered it orally to mice.

LA1 rapidly enhanced the TJ barrier in the animals, which then protected them against chemically induced colitis.

The bacterium also promoted healing of the intestinal barrier in mice with colitis.

In mice, the same Toll-like receptors mediated these enhancements of the TJ barrier.

Food manufacturers include L. acidophilus in a range of commercial brands of probiotic yogurt.

Medical News Today asked Dr. Ma whether any of these products contain the specific bacterial strain, LA1, that appears to protect the gut lining from inflammation.

Unfortunately, most probiotic companies do not list the specific strains contained in their probiotic product, Dr. Ma explained.

The Lactobacillus acidophilus strain that we referred to as LA1 is available in some of the commercial products, but it is not clear which do and do not, he said.

He added that the amount of probiotic bacteria in a product is also crucial to their biological effect, with quantities in excess of 1 billion colony-forming units per dose working best.

Dr. Ma went on to say that L. acidophilus is a component of healthy adults gut flora, but not necessarily LA1.

Because the bacterium undergoes constant genetic change, every individual will have different and often unique strains of the bacterium.

A persons diet helps determine the makeup of their gut microbiota, as recent research reported by MNT discovered.

The principal limitation of the current lab-based study was that its findings might not apply to people with inflammatory bowel conditions.

However, Dr. Ma and his colleagues hope to extend their investigation to include human volunteers, with possible clinical trials on the horizon.

The future direction of research in our laboratory is to test this in humans to see if [the bacteria] tighten the intestinal barrier and prevent or treat diseases associated with a leaky gut, said Dr. Ma.

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Probiotics: Could they help treat IBD? - Medical News Today

Patterns arent the only way to inspire coperation. In 2018, Levins team attached a plastic cuff containing progesterone, a hormone that alters the behavior of ion channels, to the stump where a frog had once had a leg. They left the cuff on for twenty-four hours, then observed for about a year. Ordinarily, a frog thats lost a leg will regrow a cartilaginous spike in its place. But the frogs in the experiment grew paddle-like limbs. About nine months later, little toes started to emerge. Levin thinks that, eventually, the same kind of cuff could be used on humans; you might wear one for a few months, long enough to persuade your body to restart its growth. (Ideally, researchers would find a way to speed development, too; otherwise, youd be stuck with a tiny arm for years.)

Levin was wary of showing me any mouse experiments. He has growntired of hearing his work compared to the sinister alchemy described in Frankenstein. That story is about scientific irresponsibility, he said. Although his research is in many ways unusual, it is ordinary in its treatment of animalsby some estimates, American researchers experiment on more than twenty-five million a year. I get two types of e-mails and phone calls, Levin told me. Some of the people call and say, How dare you do these things? for various reasonsanimal rights, playing God, whatever. And then most call and they say, What the fuck is taking you so long? From time to time, Levin receives a call from a would-be volunteer. Im going to come down to your lab, he recalled one of them saying, and Ill be your guinea pig. I want my foot back.

None of the developmental biologists I spoke with expressed any doubt that we would someday be able to regrow human limbs. They disagreed only about how long it would take us to get there, and about how, exactly, regrowth would work. Other projects explore growing body parts in labs for transplantation; 3-D-printing them whole, using tissue cells; flipping genetic switches (master regulators); or injecting stem cells into residual limbs. The solution may eventually involve a medley of techniques.

Levins vision isnt confined to limb regrowth; hes interested in many other forms of morphogenesis, or tissue formation, and in how they can be modelled using computers. He led me down the hall to a room where an elaborate, waist-high machine glowed. The device consisted of twelve petri dishes suspended above an array of lights and cameras, which were hooked up to a cluster of high-powered computers. He explained that the system was designed to measure tadpole and planarian I.Q.

In a study published in 2018, Levins team bathed frog embryos in nicotine. As they expected, the frogs exhibited a range of neural deformities, including missing forebrains. The researchers then used a piece of software called BETSEthe BioElectric Tissue Simulation Enginethat a member of the Allen Center, Alexis Pietak, had built. In this virtual world, they applied various drugs and observed their effects on both bioelectric signalling and brain development, hoping to find an intervention that would reverse the nicotines damage. The software made a prediction that one specific type of ion channel can be exploited for just such an effect, Levin said. The team tried the drug on real embryos that had been damaged by nicotine, and found that their brains rearranged themselves into the proper shape. The software, the researchers wrote, had allowed for a complete rescue of brain morphology.

The I.Q. machine gave them another way to measure the extent of the rescue. Inside it, colored L.E.D.s illuminate petri dishes from below, dividing them into zones of red and blue; when a grown tadpole ventures into the red, it receives a brief shock. Levin found that normal tadpoles uniformly learned to avoid the red zones, while those that had been exposed to nicotine learned to do so only twelve per cent of the time. But those treated with the bioelectricity-recalibrating drug learned eighty-five per cent of the time. Their I.Q.s recovered.

Researchers disagree about the role that bioelectricity plays in morphogenesis. Laura Borodinsky, a biologist who studies development and regeneration at the University of California, Davis, told me that there are many things that we still need to discover about how the process works, including how the genetic program and the bioelectrical signals are intermingled. Tom Kornberg, a biochemist at the University of California, San Francisco, studies another intercellular system that is similar to bioelectricity; it consists of morphogens, special proteins that cells release in order to communicate with one another. Kornbergs lab investigates how morphogens move among cells and tell them what to do. What is the vocabulary? Whats the language? Kornberg said, in reference to morphogenesis. There is probably more than one.

Tabin, Levins former adviser and the chair of genetics at Harvard Medical School, told me that he is agnostic about how bioelectricity should be understood. Levin describes bioelectricity as a code. But, Tabin said, theres a difference between being a trigger to initiate morphogenesis versus storing information in the form of a code. He offered an analogy. Electricity is required to run my vacuum cleaner, he said. It doesnt mean theres necessarily an electric code for vacuuming. The current flowing through the outlet isnt telling the vacuum what to do. Its just turning it on.

Levin thinks that bioelectricity is more complex than that. The right bioelectrical signal can transform a Dustbuster into a Dysonor a tail into a head. Tweaking the signal produces highly specific outcomesa head thats spiky, tubular, or hat-shapedwithout the need to adjust individual genes, ion channels, or cells. You can hack thesystem to make the changes, Levin said. Currently, theres no competing technology that can do these things.

Levins work has philosophical dimensions. Recently, he watched Ex Machinaa sci-fi film, directed by Alex Garland, in which a young programmer is introduced to Ava, a robot created by his tech-mogul boss. Unnerved by how beguilingly realistic Ava is, the hero slices his own arm open in search of wires. Since childhood, Levin, too, has wondered what we are made of; having become a father himself, he enjoys talking about such questions with his sons, who are now teen-agers. Once, when his older son was six or seven, Levin asked him how a person could be sure that he hadnt been created mere seconds ago, and provided with a set of implanted memories. I didnt really think about what the consequences for a kid might be, Levin said, laughing and a little embarrassed. He was upset for about a week.

Our intuitions tell us that it would be bad to be a machine, or a group of machines, but Levins work suggests precisely this reality. In his world, were robots all the way down. A bioelectrical signal may be able to conjure an eye out of a stomach, but eye-making instructions are contained neither in the cells genome nor in the signal. Instead, both collectively and individually, the cells exercise a degree of independence during the construction process.

The philosopher Daniel Dennett, who is Levins colleague at Tufts, has long argued that we shouldnt distinguish too sharply between the sovereign, self-determining mind and the brute body. When we spoke, Dennett, who has become one of Levins collaborators, was in bed at a Maine hospital, where he was recovering from hip surgery. I find it very comforting to reflect on the fact that billions of little agents are working 24/7 to restore my muscles, heal my wounds, strengthen my legs, he said.

In our discussion of Levins work, Dennett asked me to imagine playing chess against a computer. He told me that there were a few ways I could look at my opponent. I could regard it as a metal box filled with circuits; I could see it as a piece of software, and inspect its code; and I could relate to it as a player, analyzing its moves. In reality, of course, a chess computer offers more than three levels of explanation. The body allows more still: genetics, biophysics, biochemistry, bioelectricity, biomechanics, anatomy, psychology, and finer gradations in between, all these levels acting together, each playing an integral role. Levin doesnt claim to understand the entire system, nor does he maintain that bioelectricity is the only important level. Its just one where hes found some leverage. He likens revising an organisms body through bioelectric stimulation to launching software applications. When you want to switch from Photoshop to Microsoft Word, you dont get out your soldering iron, he said.

In modifying the body, Levin is more whisperer than micromanager; he makes suggestions, then lets the cells talk among themselves. Michael has these brilliant examples of how individual cells communicate with each other, Dennett said. But the reverse is also true: when communication breaks down, cells can go haywire. Consider cancer, Levin said. It can be created by genetic damage, but also by disruptions in bioelectric voltage. In an experiment reported in 2016, Levins team injected cancer-causing mRNA into frog embryos, and found that injected areas first lost their electrical polarity, then developed tumor-like growths. When the researchers counteracted the depolarization, some of the tumors disappeared. In Levins terms, the cancer cells had lost the thread of the wider conversation, and begun to reproduce aimlessly, without coperating with their neighbors. Once communications had been restored, they were able to make good decisions again.

Having built radios as a kid, Levin now hopes to assemble bodies from first principles. His ultimate goal is to build what he calls an anatomical compilera biological-design program in which users can draw the limbs or organs they want; the software would tell them where and how to modify an organisms bioelectric gradients. You would say, Well, basically like a frog, but Id like six legsand Id like a propeller over here, he explained. Such a system could fix birth defects, or allow the creation of new biological shapes that havent evolved in nature. With funding from DARPAa federal research agency contained within the Department of Defensehe is exploring a related possibility: building machines made from animal cells. Recently, Josh Bongard, a computer scientist at the University of Vermont, designed a computer model in which small robotic cubes connect, creating microrobots that might someday clean up toxic waste or perform microsurgery. Levin took stem and cardiac cells from frogs and sculpted them into blobs that approximated the robot designs; they began working together, matching the simulations. Bongard likened Levin to a magician pulling rabbits out of a hat. After a while, you start asking not just whats in the hat, he said, but how deep does the inside of that hat go?

On a warm afternoon, Levin and I drove out to Middlesex Fells Reservationa twenty-six-hundred-acre state park with more than a hundred miles of trails. We set out through the woods along Spot Pond, a large reservoir where people sail and kayak in the summer. As we walked, our bodies worked up a light sweat. Occasionally, Levin stopped to wonder at fungi clinging to a tree trunk, or to look under a rock for creepy crawlies. Spotting an ant, he recalled trying to feed ants as a child and being surprised at their stubbornness. He noted that planaria can have different personalitieseven clones of the same worm. He interrupted his comments on neural decoding to study a plant. Look at the colors on these berries, he said. What the hell? Ive never seen that before. It looks almost like candy. Let me get a picture of this.

I jokingly asked Levin if, when looking at nature, he saw computer code raining down, as in The Matrix. Thats a funny question, he said. I do not see the Matrix code, but Im often taking pictures or kayaking or something, and thinking about this stuff. I asked him if he saw squirrels and trees differently from the way others do. Not a squirrel, he said, because everyone recognizes it as a cognitive agenta system with beliefs and desires. But a cell or a plant, for sure.

I look everywhere, and I ask the question Whats the cognitive nature of this system? Whats it like to be a He paused. Whats your sensory world like, what decisions are you making, what memories do you have, if any? What predictions do you make? Do you anticipate future events? Slime molds can anticipate regular stimuli. I look for cognition everywhere. In some places you dont find it, and thats fine, but I think I see it broader than many people.

We stopped to look at a log and found a red splotch that appeared to be a slime mold.

I dont know what it actually is, Levin said. Im not much of a zoologist.

Bending down, he peeled off some bark: a second splotch. Researchers have found that, if a slime mold learns something and then crawls over and touches another mold, it can pass on its memory; in 2016, a pair of French scientists showed how one mold could teach another to find some hard-to-reach food through a gooey mind meld.

That, I think about all the time, Levin said. What does it mean to encode information in a way that, almost like a brain transplant, you can literally give it to another creature?

We left the log and continued on. Lichen spotted the rocks, and chipmunks chattered in the trees. There was electricity all around us.

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Is Bioelectricity the Key to Limb Regeneration? - The New Yorker

IntramuralBy Nicholas Alagna, Victoria Placentra, Prashant Rai, Janelle Weaver, and Qing Xu

Scientists from the Division of the National Toxicology Program (DNTP) uncovered a new strategy that could estimate the safety of chemicals. Using benchmark concentration (BMC) analysis with human liver cells, the team determined that different concentrations of compounds caused changes in detectable metabolites produced by liver cells. The project used metabolomics, which is the large-scale detection and measurement of metabolites the molecules that are intermediates or end products after the body breaks down food, drugs, or chemicals.

The researchers applied concentration-response modeling using BMC analysis to interpret mass spectrometry-based untargeted metabolomics data. Concentration-response modeling assesses how exposure to various concentrations of toxic chemicals and other compounds leads to changes in metabolites. The team exposed cultures of human liver cells to compounds that included relatively toxic drugs such as the cancer drug tamoxifen and the antiretroviral medication ritonavir.

Rising concentrations of drugs known to cause liver injury resulted in sharp increases in metabolic responses that were expected based on past research. By contrast, this effect did not occur for nontoxic compounds, such as sucrose and potassium chloride. According to the authors, the study shows that concentration-response modeling applied to untargeted metabolomics data accurately captures the potential of chemicals to cause liver injury. (JW)

Citation:Crizer DM, Ramaiahgari SC, Ferguson SS, Rice JR, Dunlap PE, Sipes NS, Auerbach SS, Merrick BA, DeVito MJ. 2021. Benchmark concentrations for untargeted metabolomics vs. transcriptomics for liver injury compounds in in vitro liver models. Toxicol Sci; doi: 10.1093/toxsci/kfab036 [Online 22 March 2021].

According to NIEHS researchers and their collaborators, the mosquito protein AEG12 disrupts the lipid envelope that covers some viruses. The study sheds light on the molecular mechanism AEG12 uses to inhibit virus infection, as well as offering potential new strategies to treat dangerous diseases caused by flaviviruses.

Flaviviruses a class that includes dengue, yellow fever, and zika virus are important public health concerns. These viruses are mainly transmitted by mosquitos and typically covered by a protective coating of lipids. Mosquitos produce AEG12 in response to a blood meal or flavivirus infection.

After solving the three-dimensional structure of AEG12 by X-ray crystallography, the researchers identified AEG12 as a lipid-binding protein. They further demonstrated that AEG12 was capable of rupturing membranes of red blood cells and inhibiting the replication of flaviviruses and other enveloped viruses, including human coronaviruses. AEG12 breaks open the cells or virus by swapping the lipid it carries with those in the cell membrane or virus envelop. By doing so, AEG12 contributes to both insect digestion and the antiviral immune response. The study suggests that AEG12, if engineered to target the virus only, may provide a useful tool to treat diseases caused by flaviviruses or coronaviruses. (QX)

Citation:Foo ACY, Thompson PM, Chen SH, Jadi R, Lupo B, DeRose EF, Arora S, Placentra VC, Premkumar L, Perera L, Pedersen LC, Martin N, Mueller GA. 2021. The mosquito protein AEG12 displays both cytolytic and antiviral properties via a common lipid transfer mechanism. Proc Natl Acad Sci U S A 118(11):e2019251118. (Story)

The progesterone receptor isoform B (PGR-B) mediates suppression of uterine contractibility via the Oxtr-Plcl2-Trpc3 pathway, according to NIEHS researchers and their collaborators. In humans, the progesterone receptor is a nuclear receptor with two isoforms: PGR-A and PGR-B. Elevated PGR-B gives rise to longer gestational periods, extended labor time, greater incidence of labor dystocia, or difficult birth, and a reduction in uterine contractility. PGR-A, however, promotes contractility of the uterus, without altering gestation length. To explore the in vivo role of progesterone signaling and progesterone receptor (PGR) isoforms in childbirth, the team employed transgenic mice with an overexpression of PGR-A or PGR-B in their myometrial smooth muscle.

Gene signature analyses demonstrated that PGR-A acts in a proinflammatory fashion, while PGR-B causes uterine muscle relaxation. Transcriptomic investigation revealed that PGR-B mice exhibit repression of both the Oxtr and Trpc3 genes, which both have a positive effect on uterine contractility. Furthermore, PGR-B mice displayed increased expression of the Plcl2 gene, which can reduce uterine contraction. These findings further explain precise molecular mechanisms by which PGR isoforms govern childbirth, while contributing novel insights into the maintenance of uterine dormancy by progesterone during pregnancy. (NA)

Citation:Peavey MC, Wu SP, Li R, Liu J, Emery OM, Wang T, Zhou L, Wetendorf M, Yallampalli C, Gibbons WE, Lydon JP, DeMayo FJ. 2021. Progesterone receptor isoform B regulates the Oxtr-Plcl2-Trpc3 pathway to suppress uterine contractility. Proc Natl Acad Sci U S A 118(11):e2011643118. (Story)

NIEHS scientists and collaborators at the National Cancer Institute and Duke University have uncovered the detailed mechanism by which a metabolic enzyme called PPIP5K can directly regulate tumor cell multiplication. The study helps explain the metabolic reprogramming required for multiplication of tumor cells and reveals potential targets for cancer treatment.

PPIP5K, a type of enzyme called a kinase, produces unique cellular metabolites called inositol pyrophosphates. The authors previously showed that colorectal cancer cells deficient in PPIP5K have reduced growth rate despite enhanced energy production. In this study, using high-resolution mass spectrometry and genetics, the authors demonstrated that in cancer cells, PPIP5K was critical to synthesizing nucleotides, which are universal building blocks of DNA and RNA. Absence of precursor materials to synthesize these fundamental biological units inhibits growth in PPIP5K-deficient cancer cells. Furthermore, PPIP5K kinase activity, which synthesizes inositol pyrophosphates, is critical for nucleotide synthesis and cancer cell growth.

In addition, the authors determined two specific pathways of nucleotide synthesis that are regulated by PPIP5K the serine-glycine one-carbon pathway and the pentose phosphate pathway. These results provide insight on how a single metabolic enzyme can have an overarching impact on multiple metabolic processes during tumor development. (PR)

Citation:Gu C, Liu J, Liu X, Zhang H, Luo J, Wang H, Locasale JW, Shears SB. 2021. Metabolic supervision by PPIP5K, an inositol pyrophosphate kinase-phosphatase, controls proliferation of the HCT116 tumor cell line. Proc Natl Acad Sci U S A 118(10):e2020187118.

A team of NIEHS researchers found that breast cancer relative risk increases for women near the age that an older sister was previously diagnosed with breast cancer. This study was the first to model an age-time-dependent risk for a woman based on her proximity to a siblings age of breast cancer onset.

For this study, researchers used data from the NIEHS Sister Study, which examines familial and environmental risk factors for breast cancer and other diseases in women in the United States and Puerto Rico. The cohort of participants included more than 20,000 women who had one older sister previously diagnosed with breast cancer. Researchers employed several statistical models and methods to assess the pattern of risk over time for these women as they approached and passed their sisters age of diagnosis. The risk increased by 80% when the participant reached the sisters age of diagnosis. This familial clustering indicates there could be important genetic and early environmental factors that contribute to the timing of breast cancer onset. The findings have implications for patient counseling and personalized cancer screening. (VP)

Citation:Von Holle A, O'Brien KM, Sandler DP, Weinberg CR. 2021. Evidence for familial clustering in breast cancer age of onset. Int J Epidemiol 50(1):97104.

(Nicholas Alagna is an Intramural Research Training Award [IRTA] postbaccalaureate fellow in the NIEHS Mechanisms of Mutation Group. Victoria Placentra is an IRTA postbaccalaureate fellow in the NIEHS Mutagenesis and DNA Repair Regulation Group. Prashant Rai, Ph.D., is a visiting fellow in the NIEHS Clinical Investigation of Host Defense Group. Janelle Weaver, Ph.D., is a contract writer for the NIEHS Office of Communications and Public Liaison. Qing Xu is a biologist in the NIEHS Metabolism, Genes, and Environment Group.)

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Environmental Factor - May 2021: Intramural Papers of the Month - Environmental Factor Newsletter