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‘Tabula sapiens’ multi-organ cell atlas already yielding surprises for biologists

With rare exceptions, each of the trillions of cells in our bodies carries an exact duplicate of the human genome, which contains between 20,000 and 25,000…

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With rare exceptions, each of the trillions of cells in our bodies carries an exact duplicate of the human genome, which contains between 20,000 and 25,000 protein-coding genes. But to carry out the specialized functions that make life possible, organs like the kidney, lung, heart, and brain rely on tissues built from distinctive cell types, which come about when individual cells develop to express only a particular subset of genes in the genome.

Credit: CZ Biohub

With rare exceptions, each of the trillions of cells in our bodies carries an exact duplicate of the human genome, which contains between 20,000 and 25,000 protein-coding genes. But to carry out the specialized functions that make life possible, organs like the kidney, lung, heart, and brain rely on tissues built from distinctive cell types, which come about when individual cells develop to express only a particular subset of genes in the genome.

Until recently, the diversity of gene expression across cell types, known as the transcriptome, has been difficult to decipher. But with the rapid rise of single-cell biology, scientists have created tools and techniques that reveal precisely which genes are expressed by the individual cells that make up tissues and organs. In addition to bringing a deeper understanding of normal biology, these single-cell approaches promise to open up avenues to new therapies, because diseases generally strike specific cell types.

Now, in a paper published in Science on Friday, May 13, the Tabula Sapiens Consortium, a team of more than 160 experts led by scientists at the Chan Zuckerberg Biohub, has unveiled a massive digital atlas that maps gene expression in nearly 500,000 cells from 24 human tissues and organs, including the lungs, skin, heart, and blood.

The Tabula Sapiens cell atlas is the largest to include multiple tissues from the same human donors, and the first to include histological images of the tissues, and to incorporate details of the microbial communities living alongside the human cells that make up the various compartments of the gut.

“The quality and breadth of these data are unparalleled,” said senior author Stephen Quake, D.Phil., the Lee Otterson Professor of Bioengineering and professor of applied physics at Stanford University, for whom Tabula Sapiens is the fulfillment of a 20-year “obsession.” Quake, who is also president of the CZ Biohub Network, added, “This atlas will allow scientists to ask and answer questions about human health and disease that they’ve never been able to approach before.”

The new paper is one of four major collaborative studies published in Science this week, all of which have created comprehensive and openly available cross-tissue cell atlases as part of the international Human Cell Atlas (HCA) consortium. HCA is supported by a wide range of global funders including the Chan Zuckerberg Initiative (CZI). Additional funding for Tabula Sapiens was provided through CZI’s Single-Cell Biology Program.

“This collection of work is truly inspiring,” said Jonah Cool, Ph.D., science program officer for single-cell biology at CZI. “It exceeds the expectations we set when CZI embarked on funding single-cell biology research and tool development. The technological advances that they demonstrate as well as the biological insight provided are important milestones for the field. These studies are a significant step toward large robust reference resources such as those being pursued by the Human Cell Atlas.”

The Tabula Sapiens project brought together contributions from a wide range of experts, including surgeons and tissue specialists for each organ that was included in the study. “This effort really demonstrates how much potential we can unlock when we embrace the idea of team research,” said Tabula Sapiens Consortium member Angela Oliveira Pisco, Ph.D., associate director of Data Science for CZ Biohub’s Quantitative Cell Science team. ​​“We have coordinated a precise, consistent, and comprehensive effort with more than 160 people, and that in itself is a wonderful feat for science.”

Thanks to a close partnership with Donor Network West, a nonprofit organ procurement organization in Northern California, Tabula Sapiens yields one of the broadest views available of healthy cells across the entire body. “The study maps the building blocks of biospecimens procured in a rather unique project, and demonstrates the remarkable value of non-transplanted tissues and organs for preclinical research,” said Donor Network West’s Ahmad Salehi, M.D., Ph.D., director of research.

In just one session, for example, dozens of surgeons, scientists, and recovery coordinators worked through the night to collect the cells of 17 tissues and organs from a single human donor, within an hour of the withdrawal of life support and the procurement of organs for transplantation. This rapid approach offers the opportunity to study differences in cell types without the degradation of data quality that can occur when using frozen tissue. Also, using samples from a single donor simplifies the data analysis, eliminating the need to control for genetic, age-related, and environmental differences among individuals.

“If we read enough RNA fragments, it’s like having a high-resolution telescope that can see in 25,000 dimensions,” said Bob Jones, a senior research engineer in the Department of Bioengineering at Stanford and member of the Tabula Sapiens Consortium. “It’s incredible detail.”

Tabula Sapiens uniquely includes an analysis of the products of alternative splicing, a cellular process through which differing RNA transcripts can arise from a single gene, leading to numerous protein variants. “Because multiple RNA transcripts can come from each of our 25,000 genes, it becomes very difficult to functionally characterize every single gene and what it can code in the ‘wet lab,’” said Tabula Sapiens Consortium member Julia Salzman, Ph.D., associate professor of biomedical data science and of biochemistry at Stanford. “This kind of research cannot be experimentally driven—it has to be data driven.”

In one surprise already unveiled by Tabula Sapiens, said Salzman, researchers found that sets of housekeeping genesso called because they have been thought to handle basic functions in much the same way in every celllikely have many more roles across the body than was previously thought. And in the Science paper, the team reports that CD47, a protein implicated both in cancer and in the buildup of dangerous plaques on artery walls, may differ widely in form from cell to cell, a finding that could guide the development of drugs that are more effective or have fewer side effects. The Science paper also reveals that the gut’s microbiome is “patchy” rather than uniform—Tabula Sapiens data shows that distinct microbial populations exist just a few inches apart in the digestive tract. 

“We’re already revealing important new biology that we simply would not have had the possibility of knowing about if it weren’t for Tabula Sapiens,” Salzman said. “With this atlas we have a huge opportunity to improve our understanding of the way the human body works.”

Tabula Sapiens is accessible via a free, easy-to-use data portal, which offers links to all components of the multimodal atlas. “We are committed to making our data easily and widely accessible,” said the Biohub’s Pisco. “Empowering scientists with differing expertise to take full advantage of incredible resources such as Tabula Sapiens will accelerate scientific progress.”

An open-access, user-friendly tool called cellxgene (“cell-by-gene”), developed by CZI’s Science Technology group, means that even scientists with no computational training can employ Tabula Sapiens in their work. The tool, built into the Tabula Sapiens portal, is already helping scientists tackle a variety of questions, such as understanding which cell types are most prone to deleterious gene mutations, how immune-cell populations differ in various organs, and identifying tissues vulnerable to attack by the virus that causes COVID-19.

“Our cellxgene tool is helping scientists, like those in the Tabula Sapiens Consortium, answer fundamental questions about human biology in seconds, not years,” said Phil Smoot, head of science and technology and vice president of engineering at CZI. “We’re excited to see how other scientists will take advantage of this platform to further our understanding of human health and disease.”

About CZ Biohub: The Chan Zuckerberg Biohub is a nonprofit research center that brings together physicians, scientists, and engineers from Stanford University; the University of California, Berkeley; and the University of California, San Francisco. Working at CZ Biohub are some of the brightest, boldest engineers, data scientists, and biomedical researchers, who together with our partner universities seek to understand the fundamental mechanisms underlying disease and develop new technologies that will lead to actionable diagnostics and effective therapies. Visit czbiohub.org.

About the Chan Zuckerberg Initiative: The Chan Zuckerberg Initiative was founded in 2015 to help solve some of society’s toughest challenges—from eradicating disease and improving education, to addressing the needs of our local communities. Our mission is to build a more inclusive, just, and healthy future for everyone. Visit chanzuckerberg.com.

About the Human Cell Atlas: The Human Cell Atlas (HCA) consortium is aiming to map every cell type in the human body as a basis for both understanding human health and for diagnosing, monitoring, and treating disease. An open, scientist-led consortium, HCA is a collaborative effort of researchers, institutes, and funders worldwide, with more than 2,300 members from 83 countries across the globe. Support for the HCA includes significant contributions from the Chan Zuckerberg Initiative, Wellcome Trust, the European Research Council Horizon 2020 program, the Klarman Foundation, Helmsley Charitable Trust and initiatives across the National Institutes of Health. Visit humancellatlas.org.


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Morgan Stanley: SPX could return to its pre-pandemic 3,400 level

The S&P 500 index could return to its pre-pandemic 3,400 level in the coming months that translates to another 15% downside from here, warned a Morgan…

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The S&P 500 index could return to its pre-pandemic 3,400 level in the coming months that translates to another 15% downside from here, warned a Morgan Stanley analyst on Monday.

Don’t be fooled by the bear market rally

Michael Wilson dubs the recent bounce (about 4.0%) in U.S. equities a “bear market rally” and says investors should brace for more pain ahead as inflation and supply constraints remain a significant headwind. In his note, the analyst said:

With valuations now more attractive, equity markets so oversold an rates potentially stabilizing below 3.0%, stocks appear to have begun another material bear market rally. After that, we remain confident that lower prices are still ahead.

Last week, the U.S. Bureau of Labour Statistics said inflation stood at 8.30% in April – a marginal decline versus the prior month but still ahead of the Dow Jones estimate.

How to navigate the current environment?

Wilson continues to see a recession as unlikely, but agrees that the risk of such an economic downturn has certainly gone up. The U.S. economy unexpectedly shrank 1.40% in the first quarter of 2022.

That is just another reason why equity risk premium is too low, and stocks are still overpriced. The bear market won’t be over until valuations fall to levels (14 – 15x) that discount the kind of earnings cuts we envision, or earnings estimates get cut.

He recommends increasing exposure to real estate, health care, and utilities stocks to navigate the current environment, while tech and consumer discretionary stocks remain a big “no” for him.

The post Morgan Stanley: SPX could return to its pre-pandemic 3,400 level appeared first on Invezz.

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Jelenew becomes the only sports brand as the Signature Sponsor of amfAR Gala during the 75th Festival de Cannes

Jelenew becomes the only sports brand as the Signature Sponsor of amfAR Gala during the 75th Festival de Cannes
PR Newswire
WILMINGTON, Del., May 16, 2022

Jelenew x Stéphane cycling-pants dress will be auctioned off to support the fight against AID…

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Jelenew becomes the only sports brand as the Signature Sponsor of amfAR Gala during the 75th Festival de Cannes

PR Newswire

Jelenew x Stéphane cycling-pants dress will be auctioned off to support the fight against AIDS and COVID-19

WILMINGTON, Del., May 16, 2022 /PRNewswire/ -- AmfAR announced on April 26 that Jelenew would be an amfAR Signature sponsor during the 75th Cannes Film Festival. It is reported that Jelenew is the only athletic brand among them. And Jelenew will jointly create a cycling-pants dress newlook with Stéphane Rolland, and one of the cycling-pants dresses will auction at the dinner. This helps amfAR raise funds for the American AIDS Research Foundation to contribute to the global fight against AIDS (AIDS) and COVID-19.

As a pioneer challenger in the professional cycling apparel industry, Jelenew has always adhered to the brand concept of "born for women." It focuses on solving clothing and equipment problems in professional cycling for women. It is committed to providing women with cycling products that perfectly integrate "sport functionalism, comfort, and 3D structural aesthetics". The earliest motivation for Jelenew to develop "1+1 model" detachable outer padded cycling pants (1 pair of tight-fitting leggings + 1 pair of detachable outer padded cycling shorts) came from Jelenew's social responsibility and industry mission.

In tracing the evolution history of cycling pants, the Jelenew R&D team found that although there are significant structural differences and needs between men and women. In the past 100 years, male and female riders have worn the same built-in pad cycling pants structure. They know that the "cycling pad" significantly impacts cyclists; it is the core element that affects cycling pants' comfort, sports performance, and health and hygiene index. Unscientific structure and design will obliterate women's health, comfort, and beauty. The women's cycling apparel industry urgently needs a cycling brand that is "truly made for women," which can solve the pain points of female consumers from a female perspective. So those female cyclists can enjoy the same healthy riding as male cyclists.

Jelenew's creative director Di Liu, a former Chanel Haute Couture designer, established Jelenew's research team and product development team in Paris, France. According to the different physiological structures of men and women and the differentiated needs in the riding process, he took the lead in introducing the moulage technique into the design of professional cycling pants. He led the development of the first professional cycling pants for women, the Jelenew 1+1 model: detachable outer padded cycling pants. These cycling pants subvert the built-in pad structure of traditional cycling pants. They are the first professional cycling pants truly created for women globally. 

As the world's top charity dinner, amfAR has become one of the most anticipated events during the Cannes Film Festival. Each session has attracted many international celebrities to show up to help out. As a high-profile event, amfAR is also cautious in selecting cooperative brands. The list of official partners used to be Chopard, Bvlgari,Harry Winston and Louis Vuitton, the top brands loved by celebrities. This year, in the official invitation letter of amfAR, the cutting-edge brand Jelenew is listed, and it is the only signature sponsor other than Chopard.

Di Liu said: "Jelenew is honored to be the amfAR signature sponsor during the 75th Cannes Film Festival. Over the years, this good foundation has been dedicated to advocating the impact of AIDS and HIV, providing financial support to HIV/AIDS researchers worldwide, and seeking to translate their research findings into effective policy, prevention, and a therapeutic education program that benefits the world. Each of us has the power to drive transformation. As an individual, the power may not be that great. However, when we come together, we become world game-changers. Jelenew is proud to be a part of it. "

It is understood that the cycling-pants dress newlook of Jelenew x Stéphane Rolland, which will be auctioned at the charity dinner this time, draws inspiration from the golden age of Spain in the 17th century and is a "dark cycling bride" dress look with a sense of the times. Stéphane Rolland designs the black dress on the upper body according to the paintings of Goya and Velasquez and the large black tunic with more stripes. And sleeves are embroidered with Art Deco crystals. Jelenew is based on the first professional outer padded cycling pants. It is inspired by the "Goddess of Victory" in the Louvre Museum. It draws inspiration from the Spanish 17th-century noble knight pants to create a pair of cycling pants with feminine avant-garde. This is the first cross-field cooperation between Sports Technology and Haute Couture, a milestone in the fashion field. 

It is reported that all proceeds from the cycling-pants dress newlook auction will be donated to the "amfAR AIDS Research Fund."

About JELENEW 

Jelenew is an American avant-garde cycling brand born for women. It creates the first cycling pants truly made for women in the world. It brings the groundbreaking combination of "Haute Couture and Sportswear" and carefully designs each product with "luxury moulage technique" to provide a more refined sports experience and promote a healthy lifestyle for cyclists to enjoy elegant and stylish suburban cycling.

About amfAR and amfAR Gala 

amfAR, The Foundation for AIDS Research, is one of the world's leading nonprofit organizations dedicated to the support of AIDS research, HIV prevention, treatment education, and advocacy. Since 1985, amfAR has invested nearly $617 million in its programs and has awarded more than 3,500 grants to research teams worldwide.

Celebrities frequently donate items to be auctioned off for the foundation. Past donors have included Uma Thurman, Karlie Kloss, and Milla Jovovich. The 25th annual gala embraced the #MeToo movement. 25 prominent women chaired it on stage and screen, namely: Alessandra Ambrosio, Poppy Delevigne, Linda Evangelista, Sylvia Fendi, Aileen Getty, Kate Hudson, Scarlett Johansson, Milla Jovovich, Heidi Klum, Daphna Krim (daughter of Mathilde Krim), Karolina Kurkova, Sienna Miller, Angela Missoni, Mary Parent, Katy Perry, Natasha Poly, Aishwarya Rai, Vanessa Redgrave, Joely Richardson, Carine Roitfeld, Caroline Scheufele, Irina Shayk, Lara Stone, Donatella Versace, and Michelle Yeoh. Past items auctioned have included numerous photographs by Andy Warhol, Annie Leibovitz portrait sessions, stays in fashion moguls and celebrity houses, and 53-karat diamond jewelry. Heidi Klum notably donated her Bentley S3 convertible to garner one of the highest bids at €200,000.

View original content to download multimedia:https://www.prnewswire.com/news-releases/jelenew-becomes-the-only-sports-brand-as-the-signature-sponsor-of-amfar-gala-during-the-75th-festival-de-cannes-301548494.html

SOURCE Jelenew

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World a ‘virtual tinderbox’ for catastrophic levels of severe malnutrition in children – UNICEF

World a ‘virtual tinderbox’ for catastrophic levels of severe malnutrition in children – UNICEF
Canada NewsWire
NEW YORK, May 16, 2022

Soaring food prices driven by the war in Ukraine and pandemic-fuelled budget cuts set to drive up both need for, …

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World a 'virtual tinderbox' for catastrophic levels of severe malnutrition in children - UNICEF

Canada NewsWire

Soaring food prices driven by the war in Ukraine and pandemic-fuelled budget cuts set to drive up both need for, and cost of life-saving therapeutic food treatment, the latter by up to 16 per cent

Multimedia content available to download here

NEW YORK, May 16, 2022 /CNW/ - The number of children with severe wasting was rising even before war in Ukraine threatened to plunge the world deeper into a spiralling global food crisis - and it's getting worse, UNICEF warned in a new Child Alert.

Released today, Severe wasting: An overlooked child survival emergency shows that in spite of rising levels of severe wasting in children and rising costs for life-saving treatment, global financing to save the lives of children suffering from wasting is also under threat.

"Even before the war in Ukraine placed a strain on food security worldwide, conflict, climate shocks and COVID-19 were already wreaking havoc on families' ability to feed their children," said UNICEF Executive Director Catherine Russell. "The world is rapidly becoming a virtual tinderbox of preventable child deaths and child suffering from wasting."

Currently, at least 10 million severely wasted children – or 2 in 3 – do not have access to the most effective treatment for wasting, ready-to-use therapeutic food (RUTF). UNICEF warns that a combination of global shocks to food security worldwide – led by the war in Ukraine, economies struggling with pandemic recovery, and persistent drought conditions in some countries due to climate change – are creating conditions for a significant increase in global levels of severe wasting.

Meanwhile, the price of ready-to-use therapeutic food is projected to increase by up to 16 per cent over the next six months due to a sharp rise in the cost of raw ingredients. This could leave up to 600,000 additional children without access to life-saving treatment at current spending levels. Shipping and delivery costs are also expected to remain high.

"For millions of children every year, these sachets of therapeutic paste are the difference between life and death. A sixteen per cent price increase may sound manageable in the context of global food markets, but at the end of that supply chain is a desperately malnourished child, for whom the stakes are not manageable at all," said Russell.

Severe wasting – where children are too thin for their height resulting in weakened immune systems – is the most immediate, visible and life-threatening form of malnutrition. Worldwide, at least 13.6 million children under five suffer from severe wasting, resulting in 1 in 5 deaths among this age group.

South Asia remains the 'epicentre' of severe wasting, where roughly 1 in 22 children is severely wasted, three times as high as sub-Saharan Africa. And across the rest of the world, countries are facing historically high rates of severe wasting. In Afghanistan, for example, 1.1 million children are expected to suffer from severe wasting this year, nearly double the number in 2018. Drought in the Horn of Africa means the number of children with severe wasting could quickly rise from 1.7 million to 2 million, while a 26 per cent increase is predicted in the Sahel compared to 2018.

The Child Alert also notes that even countries in relative stability, such as Uganda, have seen a 40 per cent or more increase in child wasting since 2016, due to rising poverty and household food insecurity causing inadequate quality and frequency of diets for children and pregnant women. Climate-related shocks including severe cyclical drought and inadequate access to clean water and sanitation services are contributing to the rising numbers.  

The report goes on to warn that aid for wasting remains woefully low and is predicted to decline sharply in the coming years, with little hope of recovering to pre-pandemic levels before 2028. According to a new analysis for the brief, global aid spent on wasting amounts to just 2.8 per cent of the total health sector ODA (Official Development Assistance) and 0.2 per cent of total ODA spending.

To reach every child with life-saving treatment for severe wasting, UNICEF is calling for:

  • Governments to increase wasting aid by at least 59 per cent above 2019 ODA levels to help reach to help reach all children in need of treatment in 23 high burden countries.

  • Countries to include treatment for child wasting under health and long-term development funding schemes so that all children can benefit from treatment programmes, not just those in humanitarian crisis settings.

  • Ensure that budget allocations to address the global hunger crisis include specific allocations for therapeutic food interventions to address the immediate needs of children suffering from severe wasting.

  • Donors and civil society organizations to prioritize funding for wasting to ensure a diverse, growing and a healthy ecosystem of donor support.

"There is simply no reason why a child should suffer from severe wasting – not when we have the ability to prevent it. But there is precious little time to reignite a global effort to prevent, detect and treat malnutrition before a bad situation gets much, much worse," said Russell.

"Millions of children around the world are suffering from severe wasting, the most immediate, visible and life-threatening form of malnutrition. The triple threat of COVID-19, climate change and conflict are increasing severe wasting cases impacting millions of children around the world. The conflict in Ukraine is set to plunge the world in to even deeper nutrition and food crisis, with children paying the ultimate price. But the good news is we already have the knowledge and tools to make a lasting difference between life and death for the world's most vulnerable children. Canada, as a global leader, must build on its commitments and address the growing malnutrition crisis, including support for the prevention, detection and treatment of malnutrition and wasting. Canadian leadership on the global stage will help save lives. Now is the time to take action." - David Morley, President and CEO, UNICEF Canada

Notes to Editors

About RUTF
Ready-to-use therapeutic food (RUTF) paste is a lipid-based energy dense, micronutrient paste, using a mixture of peanuts, sugar, oil, and milk powder, packaged in individual sachets. UNICEF, the global leader in RUTF procurement, purchases and distributes an estimated 75-80 per cent of the world's supply from over 20 manufacturers located across the world.

About ODA
Official development assistance (ODA) is government aid that promotes and specifically targets the economic development and welfare of developing countries. The Development Assistance Committee (DAC) of the Organization for Economic Co-operation and Development (OECD) adopted ODA as the main instrument of foreign aid in 1969 and it remains the main source of financing for development aid. ODA data is collected, verified and made publicly available by the OECD.

About UNICEF
UNICEF is the world's leading humanitarian organization focused on children. We work in the most challenging areas to provide protection, healthcare and immunizations, education, safe water and sanitation and nutrition. As part of the United Nations, our unrivaled reach spans more than 190 countries and territories, ensuring we are on the ground to help the most disadvantaged children. While part of the UN system, UNICEF relies entirely on voluntary donations to finance our life-saving work. Please visit unicef.ca and follow us on Twitter, Facebook and Instagram.

SOURCE UNICEF Canada

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