Pancreas gene finding gives new insights into human development … – EurekAlert

Understanding how the human pancreas develops is crucial to allow scientists to make insulin producingbeta cells in the quest to cure Type 1 diabetes. Now, scientists have made a unique and surprising discovery - a gene that is essential for making the pancreas in humans is not present in almost all other animals.

Beta cells within the pancreas produce insulin that regulate blood sugar. Every mammal needs the pancreatic beta-cells to survive. In established Type 1 diabetes there are no, or very few, working beta-cells.

The new finding, published in Nature Genetics, challenges assumptions about how the regulation of development evolves. Until now, scientists had assumed that genes essential for development of key organs and functions were highly conserved through evolution, meaning the genetic pathway remains the same between different species, from fish to humans. However, the gene, called ZNF808, is only found in humans, other apes such as chimpanzees and gorillas, and in some monkeys, such as macaques.

This Wellcome Trust-funded research was carried out by researchers at the University of Exeter Medical School, the University of Cambridge and the University of Helsinki in Finland. The study shows just how different humans can be to other animals often used in research, such as mice, emphasising the importance of studying the human pancreas.

Lead author Dr Elisa De Franco, of the University of Exeter Medical School, said: Our finding is really surprising this is the only example we know of where a gene that is fundamental to the development of an organ in humans and primates is not present in other animals. Youd expect a gene only found in primates to regulate a feature that is specific to primates, such as brain size, but it is not the case for this gene, which instead is involved in development of an organ shared by all vertebrates! We think this shows that there must have been an evolutionary shift in higher primates to serve a purpose.

Senior author Professor Andrew Hattersley, of the University of Exeter Medical School, said: One hypothesis that we are exploring is that the evolutionary benefit is to the pancreas in the fetus. Human babies are born through the pelvis, so they cannot stay in the uterus for a longtime as they would grow too large for birth. Instead to cope with being born early and needing to survive without continual feeding they need to be born with more fat than any other animal. This fat is laid down when the fetus pancreas produces more insulin. Our research has shown that human fetuses have more insulin-related growth than other animals.

Dr Nick Owens, of the University of Exeter Medical School, remarked This research really emphasises the importance of studying the human pancreas in order to understand and find new treatments for diabetes. Animal research is important, but it can only tell us so much. We know there are fundamental differences between humans and other animals, such as mice which are often the subject of research in this field. The human pancreas is different in how it looks, works and develops. Our genetic finding could help us understand why thats the case.

ZNF808 belongs to a family of recently evolved proteins which bind and switch off specific regions of the DNA which have also developed recently in evolutionary terms. These DNA regions were among the regions considered junk DNA with no meaningful purpose for decades, but new technology have recently allowed us to discover their functions. Our findings confirm that these regions of our DNA are playing important roles during human development.

Dr Michael Imbeault, from the University of Cambridge, said These findings show that genes like ZNF808, even if relatively recent in evolution, can have a crucial role in human development. ZNF808 is a member of the largest, but also least studied family of proteins that regulate our genome. There are hundreds of genes like ZNF808 in our DNA, many primate or even human specific, and our results demonstrate how these can be key players in human health..

The identification of ZNF808 as being involved in human pancreas development occurred after researchers at the University of Exeter examined genetic samples from patients recruited across the world who were born without a pancreas and found that they all had genetic changes resulting in loss of ZNF808. They then teamed up with colleagues at the University of Cambridge and Helsinki University to study the effect of ZNF808 loss using stem cells in the lab. The results showed that ZNF808 plays an important function early during human development when cells need to decide whether to become pancreas or liver.

Among those who shared their genetic samples was Tania Bashir, aged 12, from Luton. Her father Imran Bashir welcomed the Exeter teams progress. Having an answer to why this happened is important. Weve always wanted to know now we do. The next important step is to understand what this means to the future of science. My dream is that one day, scientists will be able to genetically modify a stem cell and grow a human pancreas, and implant that into Tania, and potentially cure her. I dont know if that will ever be possible, but I do know that this understanding is a crucial step forward.

Professor Timo Otonkoski from University of Helsinki remarked The input of people born without a pancreas was fundamental to this discovery. Nobody would have ever thought that ZNF808 played a role in pancreatic development if we hadnt found the changes in this gene in these patients. The ultimate goal of our research is for this knowledge to be translated into being able to manipulate stem cells to produce beta cells that can produce insulin in the laboratory. That could be the key to curing type 1 diabetes. Our finding is a significant step in understanding what makes the human pancreas unique, which could help progress this area.

The research was supported by the Wellcome Trust, Diabetes UK, and by the Exeter NIHR Biomedical Research Centre. The paper is entitled Primate-specific ZNF808 is essential for pancreatic development in humans and is published in Nature Genetics.

Tanias story

Tania Bashir, Twin 2, weighed just 1.1kg when she was born, via emergency caesarean section, five weeks premature, without a pancreas.

Her mother Saiqa said: From week 20 onwards the weekly scans were stressful. We were told there was a high chance that the smaller twin wouldnt make it, so we kept the fact we had a twin a secret from friends, family and even her other three siblings.

Tanias father Imran, a chartered hardware engineer in Luton, recalled: Tania weighed about as much as a bag of sugar; you could quite easily fit her in the palm of your hand They immediately realised she had neonatal diabetes, but she was also not growing or gaining weight. It took eight weeks of investigations, tests and scans to figure out she had no pancreas. Our lives have never been the same since.

As well as producing no insulin to control her blood sugar, Tania, now 12, does not produce the enzymes that break down fats, proteins and carbohydrates into smaller molecules such as triglycerides, amino acids, and sugars so they can pass through the intestine into the bloodstream. Today, with the support of her parents, she lives a relatively normal life, despite still needing a special liquid feed via a tube at night and permanently using an insulin pump. But her dad recalls the dark days of fear and uncertainty when she was small.

First, we were told she wouldnt survive till birth, then that she wouldnt survive the next few weeks I remember consciously thinking that I didnt want to get too attached, because one of us would have to be strong when she died. In the end, we stopped asking. You normally look to the medical professionals for answers, but because the condition was so rare, there just is not the experience in the UK or across the world. We were learning along with the medical professionals, pushing each other to find better solutions for Tania. We are really lucky to have a fantastic team at the Luton and Dunstable hospital.

Imran found a small network of families globally via Facebook, which provided some shared experience. When Tania was six months old, the family was connected to the research team at the University of Exeter, who specialise in genetic causes of diabetes. They visited the lab and Imran said: I remember thinking, I like what theyre trying to do here we could get an answer.

A decade later, through sequencing all the genes in Tanias DNA (a technique called whole exome sequencing) the Exeter team has identified a gene which is crucial to the development of the human pancreas and is only present in humans and some monkeys, but not in other mammals. Tanias genetic sample was one of just 13 of children born without a pancreas to enable this discovery.

Imran welcomed the progress. Having an answer is important. It draws a line under the question of why, but the journey is far from over. Unlike people with type 1 diabetes, Tanias immune system didnt attack her pancreas so a pancreas could function in her body. I believe that it might be possible to use this research to modify stem cells and grow a pancreas using Tanias own cells, which could be implanted into her. I know it sounds like science fiction, but 40 years ago, there was no such thing as the internet. Now we can share moments instantly across the world. Theres some amazing scientific progress going on in the world, and the work done by Exeter has brought us one step closer to making my dream possible.

Dr Elisa de Franco, of the University of Exeter Medical School, said: Our findings really show the importance of studying the DNA of people with rare diseases to understand how organs develop and function. We are immensely grateful to people like Tania and her family, without them none of this would be possible.

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Study Provides Clues to Developing Better Treatments for Lung … – Duke University School of Medicine

Scientists and clinicians at the Duke University School of Medicine have discovered new details about how lung tissue heals after injury caused by toxins such as air pollution or cigarette smoke.

The researchers found that a cascade of interacting steps involving two different cell types is crucial for healing. An imbalance in these steps can lead to damage that resembles emphysema or lung fibrosis, the study found.

The study, published November 2, 2023, in the journal Cell Stem Cell, paves the way for future investigations to identify possible new treatments to prevent or reverse these diseases.

"A long-standing question in the field of wound healing is how our body organs know to regrow and build the same structure after a wound," said co-senior author Purushothama Rao Tata, PhD, assistant professor of cell biology and medicine, and co-director of the Duke Regeneration Center. The study's other senior author was Aleksandra Tata, PhD, assistant research professor of cell biology.

Tata explained that lung tissue is like a big balloon draped by a structure akin to a fishnet: the extracellular matrix scaffold, which creates multiple compartments with strong, flexible walls that expand and contract as we breathe. This study focused on how the lungs rebuild this scaffold after injury.

To study this question, the scientists used a variety of methods, including single cell transcriptome analysis and other computational tools, to build "time-lapse molecular circuits" to reconstruct wound repair in mouse lungs.

"We refer to it as molecular circuits because we are not looking at one or two genes, but a collection of genes associated with a particular cell state or phenotype," Tata said. "These are like electrical circuits that all come together to switch on a light, for example. All of these genes together exert a collective function."

"Disruption of these circuits revealed key druggable molecules to target two currently incurable lung diseases emphysema and fibrosis," he said. "These diseases are like two sides of the same coin. In a lung with emphysema, we lose the walls of the scaffold. In the case of fibrosis, the wall thickness increases so they are no longer flexible."

The study revealed that after a healing "program" is activated, a cascade of events ensues, involving both epithelial cells (cells that line the lungs) and mesenchymal cells (support cells).

The researchers outlined three crucial steps or "transitional states" that happen during this process. If certain transitional states involving epithelial cells persist too long, the result is fibrosis (buildup of scar tissue). "If there is a blockade in the transition of these cell states, the result is loss of tissue that resembles emphysema," Tata said.

In a preview article highlighting the work, scientists not affiliated with the Duke study pointed out that one of the intermediate cell states identified as crucial in the healing process has previously been termed a "bad actor" in lung fibrosis research. Two drugs currently approved for fibrosis (nintedanib and pirfenodone) actually kill this cell state, Tata said. "Our study shows that treating with these drugs may actually be a bad thing," he said.

Other authors of the study are: Arvind Konkimalla, MD, PhD, currently a resident at Duke University Hospital; postdoctoral associate Satoshi Konishi, MD, PhD; laboratory research analyst Lauren Macadlo; PhD candidates Jeremy Morowitz and Zachary Farino; postdoctoral fellow Naoya Miyashita, PhD; and bioinformatician Pankaj Agarwal, all in the Duke Department of Cell Biology; Department of Pediatrics postdoctoral research associate Lea El Haddad, MD, PhD; Mai K. ElMallah, MD, associate professor of pediatrics; Christina E. Barkauskas, MD, associate professor of medicine; and Tomokazu Souma, MD, PhD, assistant professor in medicine; and Yoshihiko Kobayashi, PhD, now an assistant professor at Kyoto University in Japan.

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The largest biotech city in Europe will soon be built, with an … – BioPharma Dive

VILNIUS, Lithuania

The largest biotech city in Europe will soon be built, with an investment amounting to 7 billion euros

Northway Group is embarking on a project to establish Europes largest biotechnology hub, BIO CITY, in Vilnius, the capital of Lithuania. It includes 6 large biotechnological complexes 4 state-of-the-art GMP manufacturing plants and 2 advanced scientific research centres that will be built in an area equivalent to 10 football fields.The total investment for this biotech campus is projected to reach approximately 7 billion euros over the next decade.

A science-based economy, supported by bright minds and intelligent entrepreneurs, is the foundation for Lithuanias long-term economic prosperity. In the past, our growth was constrained by a lack of fossil resources, but today, we are boldly moving forward, relying on modern technologies. The new biotechnology hub embodies the direction of Lithuanias innovative economy. It also promises new inventions that will enable people with serious illnesses to become full members of society, thereby reducing exclusion, says the President of the Republic of Lithuania, Gitanas Nausda.

Prof. Vladas Algirdas Bumelis, founder and CEO of Northway Biotech and Celltechna, key components of the Northway Group, highlighted Lithuanias strong global standing in biotechnology. The aim of the BIO CITY project is to further solidify this position with four advanced biomanufacturing facilities and two innovative research centres, significantly boosting Lithuania's prominence in the international biotech sphere.

The Speaker of the Seimas, parliament of Lithuania, states that the new biotech city being developed in Vilnius will strengthen the competitiveness of our country. Lithuanian life sciences industry has ambitions and potential to become a global leader in this field: a leader who will significantly contribute to the development of scientific research for the well-being of man, nature and planet, and will facilitate new opportunities to deal with global health, sustainable development and other challenges, says Viktorija milyt-Nielsen.

Vision of BIO CITY: A European Biotechnology Leader

We envision BIO CITY as a frontrunner in the European biotechnology, by uniquely integrating various biotech segments into a single, synergistic ecosystem. This multifunctional complex will catalyse interdisciplinary collaborations, the quick realisation of ideas and technological advancements. Our unique model, which brings together diverse biotechnology fields in one location, is set to revolutionise the European biotech landscape, said Prof. V. A. Bumelis.

Gene Therapy Centre will Open in 2024

The first facility to open its doors in the biotech hub BIO CITY will be the Gene Therapy Centre, which is currently under construction and is being built by Northway Groups subsidiary, Celltechna. This centre, the first and so far the only one of its kind in the Baltic States, will bolster Lithuania's role in gene therapy, addressing the needs of the 280 million individuals worldwide who are affected by genetic diseases.

Our state-of-the-art facility will be instrumental in both research and production, offering new treatments for previously incurable diseases. This will not only augment our CDMO (Contract Development and Manufacturing Organisation) capabilities, but also position us for global competition and collaborations, added Prof. V. A. Bumelis.

The Gene Therapy Centre, which is expected to become operational in the second quarter of 2024, will specialise in gene therapy research and GMP manufacturing. Representing an investment of 50 million euros, the facility will span 8,000 square metres and is anticipated to create over 100 high-value jobs. The centre will work in synergy with Northway Biotech. Established in 2004, Northway Biotech is a leading provider of CDMO services in the field of biologics, with a focus on the development and manufacturing of recombinant proteins and antibodies.

A Comprehensive Lithuanian Biotech Hub

By 2030, BIO CITY will see the inauguration of five additional complexes, including centres for R&D and Virology, Life Sciences Industry Smart Services, Stem Cell Research and 3D Bioprinting, as well as two large-scale production centres for mammalian and microbial products. The entire BIO CITY complex will span an area equivalent to 10 football fields, with the total investment expected to reach around 7 billion euros over the next decade.

We will not only focus on contract development and manufacturing services, but will also invest significantly in the operation of scientific research centres. Scientific activity enhances a countrys competitiveness and generates value in various forms, beyond just the economic aspect. Modern biotechnologies, such as gene editing and cell therapies, are advancing rapidly. Lithuania can pride itself on having some of the most talented scientists and robust expertise in these areas. The development of the biotech campus in Vilnius means we are poised to foster new partnerships with innovative startups, research institutions and pharmaceutical companies on a global scale. We are actively seeking partnerships and offer a warm invitation to investors who are enthusiastic about joining this exciting venture, said Prof. V. A. Bumelis.

Upon its completion, BIO CITY is expected to offer employment to approximately 2,100 highly skilled professionals, including scientists, biotechnologists, and medical engineers.

Lithuania is Among the Leaders in the Global Biotechnology Market

The global biotechnology market, currently valued at over 1,130 billion euros, is anticipated to grow to be worth more than 2,775 billion euros by 2030. Lithuania holds a strong position in this market, ranking among the Top 35 innovative countries in the biotechnology field, according to Scientific American Worldview.

Every year, Lithuania is mentioned in the field of Life Sciences more often, and the ambitious BIO CITY project will contribute to our leadership. Our vision is coming to life we are talking about world-class Life Sciences infrastructure and a competitive sector capable of building innovative products. In 2022, companies in the sector posted combined revenues of 1.5 billion euros, while exporting their goods to more than 100 countries. Overall, Life Sciences is a leading sector in Lithuania, when it comes to creating and implementing innovative solutions, states Aurin Armonait, the Minister of the Economy and Innovation.

Over 80 life science companies operate in Lithuania, contributing about 2.5% to the countrys GDP. The Northway group, a key player in Lithuanias biotech sector, manages seven companies: five in Lithuania and one each in the UK and the US, with the US entity being recognised as the largest biotech investor from the Baltic region in recent years. Employing more than 200 specialists, these companies provide services to a diverse array of international biopharmaceutical firms, ranging from small to large enterprises, predominantly operating in both Europe and the US.

BIO CITY Contacts:

Vladas Algirdas Bumelis

CEO and Chairman of the Board

[emailprotected]

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The largest biotech city in Europe will soon be built, with an ... - BioPharma Dive

Mutation in Brain’s Immune Cells Linked to Alzheimer’s Risk – Neuroscience News

Summary: A genetic mutation affecting microglia, the brains immune cells, can increase the risk of Alzheimers disease up to threefold.

The mutation, known as TREM2 R47H/+, impairs microglia function and contributes to Alzheimers pathology. It causes inflammation, reduces debris clearance, impairs response to neuronal injury, and leads to excessive synapse pruning.

The study highlights the complex impact of this mutation, offering insights for potential therapeutic interventions in Alzheimers disease.

Key Facts:

Source: MIT

A rare but potent genetic mutation that alters a protein in the brains immune cells, known as microglia, can give people as much as a three-fold greater risk of developing Alzheimers disease.

A new study by researchers in The Picower Institute for Learning and Memory at MIT details how the mutation undermines microglia function, explaining how it seems to generate that higher risk.

This TREM2 R47H/+ mutation is a pretty important risk factor for Alzheimers disease, said study lead author Jay Penney, a former postdoc in the MIT lab of Picower ProfessorLi-Huei Tsai. Penney is now an incoming assistant professor at the University of Prince Edward Island.

This study adds clear evidence that microglia dysfunction contributes to Alzheimers disease risk.

In the study in the journalGLIA, Tsai and Penneys team shows that human microglia with the R47H/+ mutation in the TREM2 protein exhibit several deficits related to Alzheimers pathology. Mutant microglia are prone to inflammation yet are worse at responding to neuron injury and less able to clear harmful debris including the Alzheimers hallmark protein amyloid beta.

When the scientists transferred TREM2 mutant human microglia into the brains of mice, the mice suffered a significant decline in the number of synapses, or connections between their neurons, which can impair the circuits that enable brain functions such as memory.

The study is not the first to ask how the TREM2 R47H/+ mutation contributes to Alzheimers, but it may advance scientists emerging understanding, Penney said. Early studies suggested that the mutation simply robbed the protein of its function, but the new evidence paints a deeper and more nuanced picture.

While the microglia do exhibit reduced debris clearance and injury response, they become overactive in other ways, such as their overzealous inflammation and synapse pruning.

There is a partial loss of function but also a gain of function for certain things, Penney said.

Misbehaving microglia

Rather than rely on mouse models of TREM2 R47H/+ mutation, Penney, Tsai and their co-authors focused their work on human microglia cell cultures. To do this they used a stem cell line derived from skin cells donated by a healthy 75-year-old woman.

In some of the stem cells they then used CRISPR gene editing to insert the R47H/+ mutation and then cultured both edited and unedited stem cells to become microglia. This strategy gave them a supply of mutated microglia and healthy microglia, to act as experimental controls, that were otherwise genetically identical.

The team then looked to see how harboring the mutation affected each cell lines expression of its genes. The scientists measured more than 1,000 differences but an especially noticeable finding was that microglia with the mutation increased their expression of genes associated with inflammation and immune responses.

Then, when they exposed microglia in culture to chemicals that simulate infection, the mutant microglia demonstrated a significantly more pronounced response than normal microglia, suggesting that the mutation makes microglia much more inflammation-prone.

In further experiments with the cells, the team exposed them to three kinds of the debris microglia typically clear away in the brain: myelin, synaptic proteins and amyloid beta. The mutant microglia cleared less than the healthy ones.

Another job of microglia is to respond when cells, such as neurons, are injured. Penney and Tsais team co-cultured microglia and neurons and then zapped the neurons with a laser.

For the next 90 minutes after the injury the team tracked the movement of surrounding microglia. Compared to normal microglia, those with the mutation proved less likely to head toward the injured cell.

Finally, to test how the mutant microglia act in a living brain, the scientists transplanted mutant or healthy control microglia into mice in a memory-focused region of the brain called the hippocampus. The scientists then stained that region to highlight various proteins of interest.

Having mutant or normal human microglia didnt matter for some measures, but proteins associated with synapses were greatly reduced in mice where the mutated microglia were implanted.

By combining evidence from the gene expression measurements and the evidence from microglia function experiments, the researchers were able to formulate new ideas about what drives at least some of the microglial misbehavior. For instance, Penney and Tsais team noticed a decline in the expression of a purinergic receptor protein involving sensing neuronal injury perhaps explaining why mutant microglia struggled with that task.

They also noted that mice with the mutation overexpressed complement proteins used to tag synapses for removal. That might explain why mutant microglia were overzealous about clearing away synapses in the mice, Penney said, though increased inflammation might also cause that by harming neurons overall.

As the molecular mechanisms underlying microglial dysfunction become clearer, Penney said, drug developers will gain critical insights into ways to target the higher disease risk associated with the TREM2 R47H/+ mutation.

Our findings highlight multiple effects of the TREM2 R47H/+ mutation likely to underlie its association with Alzheimers disease risk and suggest new nodes that could be exploited for therapeutic intervention, the authors conclude.

In addition to Penney and Tsai, the papers other authors are William Ralvenius, Anjanet Loon, Oyku Cerit, Vishnu Dileep, Blerta Milo, Ping-Chieh Pao, and Hannah Woolf.

Funding: The Robert A. and Renee Belfer Family Foundation, The Cure Alzheimers Fund, the National Institutes of Health, The JPB Foundation, The Picower Institute for Learning and Memory and the Human Frontier Science Program provided funding for the study.

Author: David Orenstein Source: MIT Contact: David Orenstein MIT Image: The image is credited to Neuroscience News

Original Research: Open access. iPSC-derived microglia carrying the TREM2 R47H/+ mutation are proinflammatory and promote synapse loss by Jay Penney et al. Glia

Abstract

iPSC-derived microglia carrying the TREM2 R47H/+ mutation are proinflammatory and promote synapse loss

Genetic findings have highlighted key roles for microglia in the pathology of neurodegenerative conditions such as Alzheimers disease (AD). A number of mutations in the microglial protein triggering receptor expressed on myeloid cells 2 (TREM2) have been associated with increased risk for developing AD, most notably the R47H/+ substitution.

We employed gene editing and stem cell models to gain insight into the effects of the TREM2 R47H/+ mutation on human-induced pluripotent stem cell-derived microglia. We found transcriptional changes affecting numerous cellular processes, with R47H/+ cells exhibiting a proinflammatory gene expression signature.

TREM2 R47H/+ also caused impairments in microglial movement and the uptake of multiple substrates, as well as rendering microglia hyperresponsive to inflammatory stimuli. We developed an in vitro laser-induced injury model in neuronmicroglia cocultures, finding an impaired injury response by TREM2 R47H/+ microglia.

Furthermore, mouse brains transplanted with TREM2 R47H/+ microglia exhibited reduced synaptic density, with upregulation of multiple complement cascade components in TREM2 R47H/+ microglia suggesting inappropriate synaptic pruning as one potential mechanism.

These findings identify a number of potentially detrimental effects of the TREM2 R47H/+ mutation on microglial gene expression and function likely to underlie its association with AD.

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Mutation in Brain's Immune Cells Linked to Alzheimer's Risk - Neuroscience News

The Song of the Cell: An exploration of medicine and the new human – Reformed Journal

The Song of the Cell: An exploration of medicine and the new human

Siddhartha Mukherjee

Published by Scribner in 2022

496pp / $$17.89 / 978-1982117351

Ive spent more than thirty years studying cells of various types. First cells like those that make up human bodies (and their misbehaving counterpartscancer cells) and now bacterial cells. Its not at all difficult for me to tap my inner Miss Frizzle, hop on the Magic School Bus, and take a ride to the inside a cell. Its easy for me to picture ribosomes translating mRNA in the cytosol above my head, imagine importins carrying proteins through nuclear pores, and signal transduction cascades activating one protein after another like dominos falling. While I am familiar with the vivid molecular details, I know that visualizing those molecular details, much less cells, is not easy for most non-scientists. I believe that in spite of this, many people carry some curiosity about how cells work. Perhaps this curiosity arises when they encounter a disease or diagnosis, when something goes wrong with their bodies, or simply when they ponder the wonders of the natural world. At least I hope this is true. If you are someone who wonders about cells but thinks it would take too much time and effort to learn about them, The Song of the Cell: An Exploration of Medicine and the New Human is a book for you.

The author, Siddhartha Mukherjee, is an Associate Professor of Medicine in the Division of Hematology and Oncology at Columbia University where he is an oncologist and researcher, specializing in the physiology of cancer cells, stem cells in bone, and immunological therapy for cancers of the blood, such as leukemia and lymphoma. He is a prolific author with scientific publications in Nature and The New England Journal of Medicine, as well as the author of this and three other books for lay audiences. Mukherjees first book, The Emperor of All Maladies: A Biography of Cancer, won the Pulitzer Prize in 2011. His second book, The Gene: An Intimate History, was a New York Times bestseller. Mukherjees success as a popular nonfiction writer is not surprising. He has an uncanny ability to make complicated scientific processes accessible without sacrificing beauty, complexity, or accuracy. He is a master storyteller, especially gifted at using metaphors to help non-scientists picture and understand the inner workings of cells and other complicated biological processes.

What made this book especially compelling for me (and for my Cell Biology students, to whom I assigned the book last semester) was how Mukherjee was able to weave together basic cell biology with touching stories of patients who were dealing with cellular diseases as well as how our current understanding of how cells work was being used and applied to treat his patientssometimes with seemingly miraculous outcomes and sometimes with heartbreaking disappointment. He explores cancer, infertility, heart disease, bacterial and viral infections, autoimmune disease, depression, and organ/tissue transplantation in this nearly 400-page book. Despite its length, it reads quicklyperhaps because Mukherjee carefully intersperses history and complex science with personal stories of researchers, patients, and his own research.

In Emperor of All Maladies and The Gene, I found Mukherjees presentation of the science a bit too linear, giving the impression that one discovery led neatly to the next and then the next. As a scientist who spent ten years studying cancer cell biology and genetics, I know too well that the path to understanding how cells, cancer cells in particular, is laden with failures, misinterpretations, and mistakes. We zig-zag toward understanding much more than we take a straight path to it. In this book, Mukherjee makes more room for the missteps, arguments, and biases that shape scientific advances as much as the successes and collaborations, presenting what seemed to me a truer picture of how science actually works.

I didnt need much encouragement to read this book but why should a non-scientist pick it up? think this book helps a non-scientist to better appreciate the crooked path science takes toward understanding whatever it is they are studying. Readers will come away with a better understanding of how cells work and why sometimes the cells in our bodies fail. A deeper understanding of cells generates better questions when faced with health issues, greater appreciation of the available treatments and those who work to develop those treatments. Most importantly, I think readers will come away with a new level of awe at the wonder of Gods good creation and a deeper reason to worship the author of these wonder-filled, smallest units of life we call cells.

Sara Sybesma Tolsma, PhD is Professor of Biology at Northwestern College, Orange City, IA. She is currently working to discover novel bacteriophages (viruses that infect bacteria) and characterize their genomes.

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The Song of the Cell: An exploration of medicine and the new human - Reformed Journal

Ethics education among obstetrics and gynecologists in Saudi … – BMC Medical Education

Descriptions of the characteristics of the respondents

A total of 391 out of 1,000 OB/GYN practitioners responded to the survey questions by email; therefore, the response rate was 39.1%. Participants responded from all provinces of Saudi Arabia. Female respondents totaled 257 (66.4%), which was almost double the rate of male respondents. The married respondents totaled 291 (75.6%), whereas 94 (24.4%) were unmarried.

The study included participants of all ages, with approximate percentages of the participants between 30 and 50years is more than 60%.

Saudi physicians accounted for 213 (55.9%) participants and 371 (94.8%) Muslims. Approximately 247(63.1%) of the respondents were working in a tertiary government teaching hospital, whereas government non-teaching and private hospitals accounted for 107 (27%) of the participants.

Fifty-five percent of the participants were OB/GYN Board certified under different types of boards. Most of the physicians were certified by the Saudi Arabian board (18.2%), followed by the Arab board and Egyptian board (10.5%) and (6.9%) respectively; however, physicians holding Western certificates from Canada, England, US, or Indian boards were minimal in numbers.

The participants had equal percentages in relation to their tier position. The consultants and registrars in the sample numbers were 119 (30.4%) and 126 (32.23%), respectively; the remaining were residents.

Around 192 (49%) physicians had more than 10years of experience in the field of OB/GYN. Currently, 61 (15.6%) of the practitioners face 110 ethical issues monthly in their practice, while the majority 309 (79.03%) face less than one issue per month (Table 1).

Approximately 85 (21.7%) of the participants received mixed ethics education (formal ethics education and informal bioethics education), whereas 74 (18.9%) received only formal ethics education and 85 (21.7%) received only informal ethics education. In addition, 78 (19.95%) did not have any type of bioethics education.

Approximately 75% of the respondents received different types of formal and informal bioethics education. Of the respondents, 25% had no bioethics education; 137(35%) of physicians received a formal education during medical school; however, only 46 (11.8%) throughout residency programs. Self-learning was the method used for informal bioethics education in 124 (31.7%) cohorts (see Table 2 & Fig.1).

Modes of formal and informal bioethics education

No differences relatedto genderor the type of ethics education received in medical school during residency programs, postgraduate programs, conferences, courses and workshops and daily practice were detected. However, male respondents, more so than female respondents, agreed to have received ethics education in sub-specialty programs. The same finding was true regarding self-learning and online training.

Regarding marital statusand type of ethics education, no significant differences during residency programs, sub-specialty programs, in conferences, online training, in courses and workshops were found. Single respondents agreed to receive an ethics education in medical school compared to married people. Married respondents received a greater degree of informal bioethics education through daily practice and self-learning, while others received it through self-learning. There exists a significant difference between marital status and medical school (P=0.00), postgraduate programs (P=0.009), daily practice (P=0.007) and self-learning (P=0.002).

Regarding age,no significant differences were found in ethics education,except in medical schools. Respondents under 30yearsof age showed higher results (57.9%), followed by people between 3039years old (37.1%) and people aged between 4049years (28.8%). Participants>50years of age received minimum ethics education at medical school (19.4%).

No significant statistical differences regarding nationality and the type of ethics education were found except in medical schools, whereSaudi Arabian physicians (41.3%) had a significant statistical difference (P=0.007) compared to non-Saudi Arabians (28%). However, in postgraduate programs, there was a significant statistical difference (P=0.002) between non-Saudi Arabians (11.9%) and Saudi Arabians (3.8%).

There was no significant statistical difference inrelation to positionor the type of ethics education, except that residents showed the highest agreement in relation to education in medical school (P=0.00), followed by registrar/specialists and then consultants. The statement is correct regarding ethics education during sub-specialty programs (P=0.00) too.

No significant statistical difference was found between thetype of board certificateandbioethics education, except for online training (P=0.029) and daily practice (P=0.01). The participants that received Westernsub-specialist certificateshad the highest agreement to learning from daily practice, while Saudi Arabian physicians had the least (Table 1).

Significant statistical difference was found in relation tothe current workplaceand bioethics education during residency programs (P=0.015), during sub-specialty programs (P=0.04), in postgraduate programs (P=0.025) and Online learning (P=0.004). Online learning had a higher percentage of physicians who worked in private hospitals.

There was no significant statistical difference in relationto experienceand the type of ethics education, except for education in medical schools (P=0.00) and during sub-specialty programs (P=0.005). Physicians having experience of<5years showed the highest positive agreement followed by participants of 510years, and then>10years. A high percentage of less experienced physicians had bioethics education in medical college, while those with more than 10years' experience were found to have a significant statistical difference from those who had bioethics education through subspecialty training.

There was a significant statistical difference between the number of ethical challenges per month and bioethics education in medical school (P=0.007), in courses and workshops (P=0.009) and daily practice (P=0.00). Most of the respondents with ethics education from medical school and in courses and workshops had faced more than 10 challenges per month (47.60% and 28.60% respectively), whereas respondents with ethics education from daily practice had a maximum of 110 challenges per month (39%) (Table 1).

There was no significant statistical difference in relationto sub-specialtyand the type of ethics education except for the general OB/GYN, which showed the least agreement compared to other types of subspecialties. The same finding is true regarding online training too.

No significant statistical difference was observed between the type of ethics education and ethical principles. Irrespective of the mode of ethics education, most of the respondents had a positive attitude towards various ethical principles. The highest positive attitude was towards respecting privacy of people and respecting confidentiality. Solidarity And Cooperation had the least positive attitude across all modes of ethics education (see Table 3).

The attitude of the OB/GYNs towards various ethical challenges in their daily practice were investigated. No statistical significance was observed between various forms of formal ethics education and ethical challenges, except there exists a significant statistical difference between post-graduate program and termination of pregnancy for non-medical (P=0.05) and between residency program and contraception issues (P=0.021). The respondents with postgraduate ethics education had a high positive response (agreed and strongly agreed, 31%) to the ethical challenge "Termination of pregnancy for a non-medical reason," and the respondents without residency program ethics education had a high positive response (agreed and strongly agreed, 46%) to the ethical challenge "contraception issues."

Pertaining to the informal mode of ethics education, significant statistical difference was observed between courses and workshops and paternity issues (P=0.006); female consent (P=0.004); breach of confidentiality (P=0.007). There also exists a significant difference between breach of confidentiality and conference and workshop (P=0.007) and daily practice (P=0.023). The respondents without courses and workshop mode of ethics education had agreed to the ethical challenges of paternity issues (33.92%), female consent (58%), and breach of confidentiality (33.6%). The respondents who did not have ethics education through conference (33%) and daily practice (33.8%) also agreed to the ethical challenge breach of confidentiality (Table 4).

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Ethics education among obstetrics and gynecologists in Saudi ... - BMC Medical Education

Victorian research institute takes lead in nation-first stem cell therapy … – Australian Manufacturing

The Murdoch Childrens Research Institute (MCRI) is launching an Australian-first stem cell therapy trial aimed at addressing a rare genetic disorder, the Victorian Government announced in a media release.

Minister for Medical Research Ben Carroll made a visit today to the MCRI, located within the premises of Parkvilles Royal Childrens Hospital (RCH) to make the announcement.

The clinical trial is set to provide hope for young Australians grappling with RAG-1 deficient Severe Combined Immunodeficiency (RAG-1 SCID), an exceptionally rare genetic condition.

The trial is an extension of ongoing research at Leiden University Medical Centre in the Netherlands and is made possible through the support of the Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW consortium) in partnership with the Melbourne Childrens Trials Centre.

The Victorian Government is demonstrating its unwavering commitment to this vital research endeavour by investing $1 million in the MCRI.

This investment will also further enhance the MCRIs stem cell research and regenerative medicine capabilities, bolstering its pivotal role within the new reNEW consortium.

Minister for Medical Research Ben Carroll expressed his enthusiasm for the trial, emphasising that it would provide young Australians born with RAG-1 SCID the prospect of leading a happy, healthy and long life.

Victoria is renowned as a global centre for medical research and the Murdoch Childrens Research Institute is just one example of the incredible work being done that is having a positive impact on peoples lives, the minister noted.

In particular, RAG-1 SCID is a genetic condition that results in affected children being born without immune cells capable of fighting infections.

This leaves these young patients exceptionally vulnerable to common illnesses, often leading to tragic outcomes as most infants born with this rare genetic condition succumb to infections during their first years of life.

The clinical trial involves extracting stem cells from the participants bone marrow, genetically modifying them to incorporate a healthy copy of the RAG-1 gene, and then injecting them into the childs bloodstream.

These modified cells will develop into healthy white blood cells, thus establishing a fully functional immune system.

While RAG-1 SCID is rare, each year sees several babies diagnosed with this condition in Australia, as reported by the Victorian Government.

In the 2023/24 Victorian Budget, $9 million was allocated to genetic testing to facilitate targeted treatment options for children, increase treatment accessibility, and enhance outcomes for patients with rare diseases and cancer who require specialised therapies.

The MCRI, one of Victorias 12 independent medical research institutes, holds the distinction of being the largest child health research institute in Australia and is ranked as the third highest globally.

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Victorian research institute takes lead in nation-first stem cell therapy ... - Australian Manufacturing

Research Fellow (Aging and Cancer Stem Cell Laboratory … – Times Higher Education

Job Description

The National University of Singapore invites applications for Research Fellow under Aging and Cancer Stem Cell Laboratory in the Department of Physiology,Yong Loo Lin School of Medicine.

We have a deep interest in identifying genes and pathways that are crucial for normal and cancer brain stem cell function, as such studies have implications in regenerative medicine and cancer. Appointments will be made on a one-yearcontract basis, with the possibility of extension with good performance.

Purpose of the post

The Research Fellow (RF) will be responsible to, and work closely with the Principal Investigator and study team members to ensure the successful completion of the experiments on time. The RFs principal role will be to design and execute experiments, analyze data, write manuscripts and manage experimental protocols.

Main Duties and Responsibilities

The Research Fellow (RF) will be conducting research related to brain stem cell function in the normal brain and during malignancy. The RF will be able to:

Qualifications

The applicant should possess:

Remuneration will be commensurate with the candidates qualifications and experience.

Only shortlisted candidates will be notified.

More Information

Location: Kent Ridge Campus Organization: Yong Loo Lin School of Medicine Department: Physiology Employee Referral Eligible: No Job requisition ID: 20169

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Research Fellow (Aging and Cancer Stem Cell Laboratory ... - Times Higher Education

Mesenchymal Stem Cell Therapy Shows Cognitive and Biomarker … – Neurology Live

A new interim analysis of an open label trial presented at the 2023 MSMilan, the 9th Joint ECTRIMS-ACTRIMS meeting, held October 1113, in Milan, Italy, revealed significant beneficial effects on cognition and on objective biomarkers of neuroinflammation and neurodegeneration, among patients with progressive multiple sclerosis (MS) treated with repeated intrathecal (IT) injections of autologous mesenchymal stem cells (MSC).1

In 15 tested patients treated by at least 2 injections of MSC, 9 such patients improved between 5% and 18% in 25 feet walking. In addition, the average standard score of 4 cognitive tests taken by patients improved from 0.11 at baseline to 0.33 following 3 MSC injections over a year. Among 22 patients who received at least 1 MSC treatment, 13 of them showed improvement in the Symbol Digit Modalities Test (SDMT) scores, one of the cognitive tests. Notably, 6 of 17 treated patients improved by more than 4 degrees in SDMT in 3 consecutive tests over a year.

In this analysis, lead author, Petrou Panayiota, MD, senior neurologist, Unit of Neuroimmunology and Multiple Sclerosis Center and The Agnes-Ginges Center for Neurogenetics at Hadassah University Hospital in Jerusalem, Israel, and colleagues primarily evaluated the effect of repeated MSC transplantations on cognition in patients with progressive MS. Additionally, the researchers investigated objective serum biomarkers of neuroinflammation and neurodegeneration, specifically neurofilaments light chain (NfL) and glial fibrillary acidic protein (GFAP) with the therapy.

The open-label extension enrolled 48 patients with either secondary progressive MS or primary progressive MS who participated in the previous double-blind trial (NCT02166021) with MSC injections. The researchers used 4 cognitive tests including the SDMT, California Verbal Learning Test, Brief Visuospatial Memory Test, and Controlled Oral Word Association Test to assess patients at baseline before treatment, and at 4-5 time points following the first MSC-injection. At the same time, researchers also tested for serum NfL and GFAP levels using Quanterix technology (SIMOA).

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Among available data, 17 patients were treated with at least 2 intrathecal injections of MSC between 3 and 6 months apart, and 12 patients received 3 MSC injections. For treated patients, NfL levels reduced from a mean of 15.7 pmol/ml at baseline to 12.8 pmol/ml during the post-treatment year while GFAP levels also reduced from 191.4 pmol/ml at baseline to 155.4 pmol/ml.

In the previous double-blind randomized study conducted by Petrou and colleagues, IT injection of autologous bone marrow derived MSC showed robust clinical and radiological effects in patients with active and progressive MS.2 Enrolled patients had evidence of either clinical worsening or activity during the previous year between 2015 and 2018 andwere randomized into 3 groups: IT or intravenous (IV) autologous MSCs (1 106/kg) or sham injections.

After 6 months, half of the patients from the MSC-IT and MSC-IV groups were retreated with MSCs, and the other half with sham injections. Patients initially assigned to sham treatment were divided into 2 subgroups and treated with either MSC-IT or MSC-IV. After 14 months of the study, instigators did not observe any serious treatment-related safety adverse events. Significantly fewer patients experienced treatment failure in the MSC-IT and MSC-IV groups compared with those in the sham-treated group (6.7%, 9.7%, and 41.9%, respectively, P = .0003 and P = .0008).

During the 1-year follow-up, 58.6% and 40.6% of patients treated with MSC-IT and MSC-IV, respectively, had no evidence of disease activity compared with 9.7% in the sham-treated group (P <.0001 and P <.0048, respectively). In addition, the MSC-IT transplantation induced additional benefits on the relapse rate, on the monthly changes of the T2 lesion load on MRI, and on the timed 25-foot walking test, 9-hole peg test, optical coherence tomography, functional MRI and cognitive tests. Overall, treatment with MSCs was well-tolerated and induced short-term beneficial effects, especially in the patients with active disease. Notably, the IT administration was more efficacious than the intravenous in several parameters of the disease.

Click here for more coverage of MSMilan 2023.

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Mesenchymal Stem Cell Therapy Shows Cognitive and Biomarker ... - Neurology Live

Plant Stem Cells Market to Attain a Revenue of US$ 801.9 Million By … – Medgadget

In 2022, The Global Plant Stem Cells Market revenue was US$ 371.4 million and is projected to attain a valuation of US$ 801.9 million by 2031, growing at a CAGR of 8.93% during the forecast period from 2023 to 2031.

The plant stem cells market is still emerging, constantly updated with new developments and studies exploring their potential. This rise in demand is a result of rapidly expanding industries mainly cosmetics and pharmaceuticals using plant stem cells capacity for regeneration. This product helps the end-users to improve their product quality and capture the attention of consumers. As a result, a large number of manufacturers are including plant stem cells in their product formulations to get the desired result. In line with this, the market has witnessed tremendous growth in research and development activities to explore growth potential and revenue opportunities in products that are used for skin regeneration, whitening, tanning, moisturizing, and cleansing.

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As per the recent report published by Astute Analytica the global cosmetics market was valued at US$ 262 billion in 2022 and will witness the highest CAGR of 4.3% during the projected period. Also, the cosmetic industry is contributing more than 47% of revenue to the global plant stem cells market. As per our recent survey on consumer trend analysis, it was found that 65% of customers globally prefer cosmetic chemicals originating from plants. Thus, demonstrating a substantial shift in end-user behavior. In line with this, prominent businesses namely Oriflame, Mibelle AG Biochemistry, EJO Skin, etc., use plant stem cells in their products.

Shift in Trends: Manufacturers Obtaining Ethically Sourced Plant Stem Cells

It was prominently observed that over 63% of customers globally showed concern about the origin of plant stem cells utilized in products and their potential effects on the environment. As a result, manufacturers have started taking steps to meet the consumer demand for ethical sourcing and biodiversity protection. For instance, the market witnessed more than 25% growth in the companies that have opted for certificates for products that were sourced ethically in 2022. Unhwa Corporation, Stempeutics, and STEMCELL Technologies are some of the companies that obtain plant stem cells ethically. Additionally, eco-friendly sourcing is used in products like PhytoCellTecTM Goji and Patagonia Berry Stem Cell Mask.

Asia Pacific Contribute Over 23% of Revenue Share: Making it a Largest Market

The Asia Pacific plant stem cells market accounts for nearly 23% of revenue share. Also, the region contributes 9% of annual growth to the market, with China, South Korea, and India being the main contributors.

Comparing Asian cosmetic firms to their Western counterparts on a global scale, the inclusion of products derived from plant stem cells has increased by 20%. Asia Pacific is now a huge contributor to the market expansion as this is consistent with the cultural preference for botanical ingredients.

According to our recent survey on consumer analysis, an astounding 80% of Asians still use traditional herbal treatments. In line with this, the cultural proclivity is driving the acceptance of plant stem cell products. It has been observed that consumers are ready to pay premium price for buying cosmetics products having plant stem cells. For instance, the cost of a tomato anti-oxidant cream is US$ 10, while a stem cell anti-oxidant cream, which contains extracts from tomato plant stem cells, can be priced at US$ 50, even though both creams have the same fundamental ingredients. This increase in commercialization opportunities has fueled the industrys interest in creating additional stem cell products and services directly marketed to consumers.

For the full report, please follow this link:-https://www.astuteanalytica.com/industry-report/plant-stem-cells-market

The global plant stem cell market segmentation focuses on Location, Application, End-User, and Region.

By Location

By Application

By End User

By Region

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About Astute Analytica

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Plant Stem Cells Market to Attain a Revenue of US$ 801.9 Million By ... - Medgadget