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Researchers from UT Southwestern Medical Center have developed a first-of-its-kind nanoparticle vaccine immunotherapy that targets several different cancer types. The nanovaccine consists of tumor antigens – tumor proteins that can be recognized by the immune system – inside a synthetic polymer nanoparticle. Nanoparticle vaccines deliver minuscule particulates that stimulate the immune system to mount an immune response. The goal is to help people’s own bodies fight cancer. “What is unique about our design is the simplicity of the single-polymer composition that can precisely deliver tumor antigens to immune cells while stimulating innate immunity. These actions result in safe and robust production of tumor-specific T cells that kill cancer cells,” said Dr. Jinming Gao, a Professor of Pharmacology and Otolaryngology in UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center. A study outlining this research, published online in Nature Nanotechnology, reported that the nanovaccine had anti-tumor efficacy in multiple tumor types in mice. The research was a collaboration between the laboratories of study senior authors Dr. Gao and Dr. Zhijian “James” Chen, Professor of Molecular Biology and Director of the Center for Inflammation Research. The Center was established in 2015 to study how the body senses infection and to develop approaches to exploit this knowledge to create new treatments for infection, immune disorders, and autoimmunity. Typical vaccines require immune cells to pick up tumor antigens in a “depot system” and then travel to the lymphoid organs for T cell activation, Dr. Gao said. Instead, nanoparticle vaccines can travel directly to the body’s lymph nodes to activate tumor-specific immune responses. “For nanoparticle vaccines to work, they must deliver antigens to proper cellular compartments within specialized immune cells called antigen-presenting cells and stimulate innate immunity,” said Dr. Chen, also a Howard Hughes Medical Institute Investigator and holder of the George L. MacGregor Distinguished Chair in Biomedical Science. “Our nanovaccine did all of those things.” In this case, the experimental UTSW nanovaccine works by activating an adaptor protein called STING, which in turn stimulates the body’s immune defense system to ward off cancer. The scientists examined a variety of tumor models in mice: melanoma, colorectal cancer, and HPV-related cancers of the cervix, head, neck, and anogenital regions. In most cases, the nanovaccine slowed tumor growth and extended the animals’ lives. Other vaccine technologies have been used in cancer immunotherapy. However, they are usually complex – consisting of live bacteria or multiplex biological stimulants, Dr. Gao said. This complexity can make production costly and, in some cases, lead to immune-related toxicities in patients. With the emergence of new nanotechnology tools and increased understanding of polymeric drug delivery, Dr. Gao said, the field of nanoparticle vaccines has grown and attracted intense interest from academia and industry in the past decade. “Recent advances in understanding innate and adaptive immunity have also led to more collaborations between immunologists and nanotechnologists,” said Dr. Chen. “These partnerships are critical in propelling the rapid development of new generations of nanovaccines.” The investigative team is now working with physicians at UT Southwestern to explore clinical testing of the STING-activating nanovaccines for a variety of cancer indications. Combining nanovaccines with radiation or other immunotherapy strategies such as “checkpoint inhibition” can further augment their anti-tumor effectiveness. Study lead authors from UT Southwestern were Dr. Min Luo, research scientist; Dr. Hua Wang, Instructor of Molecular Biology; and Dr. Zhaohui Wang, postdoctoral fellow. Other UTSW researchers involved included graduate students Yang Li, Chensu Wang, Haocheng Cai, and Mingjian Du; Dr. Gang Huang, Instructor of Pharmacology and in the Simmons Comprehensive Cancer Center; Dr. Xiang Chen, research specialist; Dr. Zhigang Lu, Instructor of Physiology; Dr. Matthew Porembka, Assistant Professor of Surgery and a Dedman Family Scholar in Clinical Care; Dr. Jayanthi Lea, Associate Professor of Obstetrics and Gynecology and holder of the Patricia Duniven Fletcher Distinguished Professorship in Gynecological Oncology; Dr. Arthur Frankel, Professor of Internal Medicine and in the Simmons Comprehensive Cancer Center; and Dr. Yang-Xin Fu, Professor of Pathology and Immunology, and holder of the Mary Nell and Ralph B. Rogers Professorship in Immunology. Their work was supported by the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, a UTSW Small Animal Imaging Resource grant and a Simmons Comprehensive Cancer Center support grant.


News Article | April 24, 2017
Site: phys.org

The structure of an important protein complex that regulates the metaphase-to-anaphase transition during cell cycle progression has been solved using cryo-electron microscopy (cryo-EM) at Diamond Light Source. The structural study, detailed in Nature Structural and Molecular Biology, has provided valuable insights into the inner workings of the separase–securin complex.


AUSTIN, Texas--(BUSINESS WIRE)--On April 8, hundreds gathered at The University of Texas Golf Club for a common goal, raising awareness and funds to help CureDuchenne in its mission to find a cure for Duchenne muscular dystrophy, a fatal genetic disease. The eighth annual Champions to CureDuchenne, emceed by Jim Spencer, chief weathercaster at KXAN, raised more than $378,000 in the hopes of improving the lives of all those affected by Duchenne. Those with Duchenne often lose their ability to walk by their mid-teens and the disease claims their lives by their mid-20s. Over the years, CureDuchenne has advanced drug development in Duchenne treatment thanks to the champions who attend and support the Champions to CureDuchenne Gala. Eight years ago, former University of Texas coach Mack Brown and his wife Sally teamed up with Tim and Laura Revell, parents of two boys with Duchenne, and created Champions to CureDuchenne. Since its inception, the annual event has raised more than a million dollars to find a cure for this devastating disease. “Every year, champions gather to bring hope to boys with Duchenne and their families,” said Tim Revell. “Now more than ever, we must commit to finding a cure. As advancements are made, we must continue to push forward in our fight. With the help of all CureDuchenne Champions, we are able to invest in the future survival of all those with Duchenne.” The proceeds of the event will fund gene editing research that could be transformational for Duchenne patients. This one-time treatment using CRISPR/Cas9 technology has the potential to correct a majority of the genetic mutations in Duchenne. This research is being conducted by Dr. Eric Olson, Professor and Chairman of the Department of Molecular Biology at the University of Texas Southwestern Medical Center. Presented by Fired Up Charity Foundation, the eighth annual Champions to CureDuchenne included gracious event sponsors, Revenew International, Brightstar Care of Austin, Designer Floors of Texas, Fitzpatrick Insurance Solutions, H-E-B Tournament of Champions, NFL Alumni Austin, Reese Family Foundation, Russell Korman, Sarepta Therapeutics, Small Luxury Hotels of the World, Summit Stoneworks, and Waypoint Lighting. The fun-filled event featured cocktails, dinner, casino, silent and live auction. CureDuchenne is the leading nonprofit focused on funding research to find a cure for Duchenne muscular dystrophy, a disease that affects more than 300,000 boys worldwide. CureDuchenne’s mission is to extend and improve the lives of those affected by Duchenne. With support from CureDuchenne, nine research projects have advanced to human clinical trials. CureDuchenne provides the Duchenne community with resources on the best standard of care through its CureDuchenne Cares program. For more information, please visit CureDuchenne.org and follow us on Facebook, Twitter, Instagram and YouTube.


But of course, finding evidence of life is no easy task. In addition to concerns over contamination, there is also the and the hazards the comes with operating in extreme environments – which looking for life in the solar system will certainly involve. All of these concerns were raised at a new FISO conference titled "Towards In-Situ Sequencing for Life Detection", hosted by Christopher Carr of MIT. Carr is a research scientist with MIT's Department of Earth, Atmospheric and Planetary Sciences (EAPS) and a Research Fellow with the Department of Molecular Biology at Massachusetts General Hospital. For almost 20 years, he has dedicated himself to the study of life and the search for it on other planets. Hence why he is also the science principal investigator (PI) of the Search for Extra-Terrestrial Genomes (SETG) instrument. Led by Dr. Maria T. Zuber – the E. A. Griswold Professor of Geophysics at MIT and the head of EAPS – the inter-disciplinary group behind SETG includes researchers and scientists from MIT, Caltech, Brown University, arvard, and Claremont Biosolutions. With support from NASA, the SETG team has been working towards the development of a system that can test for life in-situ. Introducing the search for extra-terrestrial life, Carr described the basic approach as follows: "We could look for life as we don't know it. But I think it's important to start from life as we know it – to extract both properties of life and features of life, and consider whether we should be looking for life as we know it as well, in the context of searching for life beyond Earth." Towards this end, the SETG team seeks to leverage recent developments in in-situ biological testing to create an instrument that can be used by robotic missions. These developments include the creation of portable DNA/RNA testing devices like the MinION, as well as the Biomolecule Sequencer investigation. Performed by astronaut Kate Rubin in 2016, this was first-ever DNA sequencing to take place aboard the International Space Station. Building on these, and the upcoming Genes in Space program – which will allow ISS crews to sequence and research DNA samples on site – the SETG team is looking to create an instrument that can isolate, detect, and classify any DNA or RNA-based organisms in extra-terrestrial environments. In the process, it will allow scientists to test the hypothesis that life on Mars and other locations in the solar system (if it exists) is related to life on Earth. To break this hypothesis down, it is a widely accepted theory that the synthesis of complex organics – which includes nucleobases and ribose precursors – occurred early in the history of the solar system and took place within the Solar nebula from which the planets all formed. These organics may have then been delivered by comets and meteorites to multiple potentially-habitable zones during the Late Heavy Bombardment period. Known as lithopansermia, this theory is a slight twist on the idea that life is distributed throughout the cosmos by comets, asteroids and planetoids (aka. panspermia). In the case of Earth and Mars, evidence that life might be related is based in part on meteorite samples that are known to have come to Earth from the Red Planet. These were themselves the product of asteroids striking Mars and kicking up ejecta that was eventually captured by Earth. By investigating locations like Mars, Europa and Enceladus, scientists will also be able to engage in a more direct approach when it comes to searching for life. As Carr explained: "There's a couple main approaches. We can take an indirect approach, looking at some of the recently identified exoplanets. And the hope is that with the James Webb Space Telescope and other ground-based telescopes and space-based telescopes, that we will be in a position to begin imaging the atmospheres of exoplanets in much greater detail than characterization of those exoplanets has [allowed for] to date. And that will give us high-end, it will give the ability to look at many different potential worlds. But it's not going to allow us to go there. And we will only have indirect evidence through, for example, atmospheric spectra." Mars, Europa and Enceladus present a direct opportunity to find life since all have demonstrated conditions that are (or were) conducive to life. Whereas there is ample evidence that Mars once had liquid water on its surface, Europa and Enceladus both have subsurface oceans and have shown evidence of being geologically active. Hence, any mission to these worlds would be tasked with looking in the right locations to spot evidence of life. On Mars, Carr notes, this will come down to looking in places there there is a water-cycle, and will likely involve some a little spelunking: "I think our best bet is to access the subsurface. And this is very hard. We need to drill, or otherwise access regions below the reach of space radiation which could destroy organic materiel. And one possibility is to go to fresh impact craters. These impact craters could expose material that wasn't radiation-processed. And maybe a region where we might want to go would be somewhere where a fresh impact crater could connect to a deeper subsurface network – where we could get access to material perhaps coming out of the subsurface. I think that is probably our best bet for finding life on Mars today at the moment. And one place we could look would be within caves; for example, a lava tube or some other kind of cave system that could offer UV-radiation shielding and maybe also provide some access to deeper regions within the Martian surface." As for "ocean worlds" like Enceladus, looking for signs of life would likely involve exploring around its southern polar region where tall plumes of water have been observed and studied in the past. On Europa, it would likely involve seeking out "chaos regions", the spots where there may be interactions between the surface ice and the interior ocean. Exploring these environments naturally presents some serious engineering challenges. For starters, it would require the extensive planetary protections to ensure that contamination was prevented. These protections would also be necessary to ensure that false positives were avoided. Nothing worse than discovering a strain of DNA on another astronomical body, only to realize that it was actually a skin flake that fell into the scanner before launch! And then there are the difficulties posed by operating a robotic mission in an extreme environment. On Mars, there is always the issue of solar radiation and dust storms. But on Europa, there is the added danger posed by Jupiter's intense magnetic environment. Exploring water plumes coming from Enceladus is also very challenging for an orbiter that would most likely be speeding past the planet at the time. But given the potential for scientific breakthroughs, such a mission it is well worth the aches and pains. Not only would it allow astronomers to test theories about the evolution and distribution of life in our solar system, it could also facilitate the development of crucial space exploration technologies, and result in some serious commercial applications. Looking to the future, advances in synthetic biology are expected to lead to new treatments for diseases and the ability to 3-D print biological tissues (aka. "bioprinting"). It will also help ensure human health in space by addressing bone density loss, muscle atrophy, and diminished organ and immune-function. And then there's the ability to grow organisms specially-designed for life on other planets (can you say terraforming?) On top of all that, the ability to conduct in-situ searches for life on other Solar planets also presents scientists with the opportunity to answer a burning question, one which they've struggled with for decades. In short, is carbon-based life universal? So far, any and all attempts to answer this question have been largely theoretical and have involved the "low hanging fruit variety" – where we have looked for signs of life as we know it, using mainly indirect methods. By finding examples that come from environments other than Earth, we would be taking some crucial steps towards preparing ourselves for the kinds of "close encounters" that could be happening down the road. Explore further: The search for extraterrestrial life in the water worlds close to home


News Article | April 24, 2017
Site: www.eurekalert.org

PHILADELPHIA -- (April 24, 2017) -- The RNA editing protein ADAR1 was first discovered several decades ago. Now, scientists at The Wistar Institute have identified a new function for the protein: It stops cells that have been exposed to stressors such as ultraviolet (UV) radiation from dying. Study results were published recently in Nature Structural & Molecular Biology. There are two forms of the ADAR1 protein, ADAR1p110 and ADAR1p150. Several biological functions for ADAR1p150 have been revealed, but little is known about the role of ADAR1p110 in vivo. The new research shows that ADAR1p110 regulates the response of cells to certain stressors, including UV radiation, by protecting them from dying as a result of a process called apoptosis, a form of programmed cell death. "Before we started this work, we knew very little about the function of ADAR1p110 in vivo," said Kazuko Nishikura, Ph.D., professor in the Gene Expression and Regulation Program at The Wistar Institute and senior author of the study. "We knew that it could edit RNA, a polymeric molecule key for decoding the genetic material in a cell, but we did not know if this was important for its biological function." "We were surprised to find that ADAR1p110 has an important biological role as a stress-response protein, and that this function is independent of its ability to edit RNA," she added. To identify the functions of ADAR1p110, Nishikura and colleagues reasoned that the cellular location of the protein must be linked to its function. They found that when cells were exposed to stressors such as UV radiation, ADAR1p110 transiently moved from its normal location in the nucleoplasm and nucleoli of a cell into the cytoplasm. The researchers then characterized the pathway controlling this change in cellular distribution, finding that it involved a protein called MAP kinase p38, which was already known to have a role in regulating death or survival of stressed cells. Once in the cytoplasm, Nishikura and colleagues showed that ADAR1p110 protects a defined set of mRNAs from degradation. Many of these mRNAs decode genes involved in preventing apoptotic cell death, leading the researchers to conclude that ADAR1p110 protects cells from stress-induced apoptosis by protecting anti-apoptotic mRNAs from degradation. "Now that we have a well-defined function for ADAR1p110, we can work to understand its role in postnatal development and disease, in a particular cancer," added Nishikura. This work was supported by National Institutes of Health grants R01GM040536 and R01CA175058; the Macula Vision Research Foundation; and Japan Society for the Promotion of Science grants S13204 and JSPS 2010-22. Core support for The Wistar Institute was provided by the Cancer Center Support Grant P30CA010815. Co-authors of this study from The Wistar Institute are: Massayuki Sakurai, Yusuke Shiromoto, Hiromitsu Ota, Chunzi Song, Andrew V. Kossenkov, Jayamanna Wickramasinghe, Louise C. Showe, Emmanuel Skordalakes, Hsin-Yao Tang, and David W. Speicher. The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. wistar.org.


News Article | April 18, 2017
Site: www.prweb.com

In the National Leadership Academies video series Ivy League students talk straight with America’s best and brightest high school students to give them a realistic idea of what lies ahead. The second interview has been released on the Academy YouTube page. Princeton students and award-winning aspiring medical scientist, Janelle Tam has teamed up with the National Leadership Academies to provide current high school students an exclusive insight at how Ivy-League university students have accomplished their goals to date and what students can do to achieve and reach their ambitions. Janelle Tam is the winner of the 2012 Sanofi BioGENEius Challenge of Canada. She is a current senior at Princeton University where she is majoring in Molecular Biology with a certificate in Global Health and Health Policy. Tam is a speaker and mentor for students at the Congress of Future Medical Leaders held outside Boston, Massachusetts. The Congress of Future Medical Leaders is an annual gathering of the nation’s best and brightest future medical leaders who possess leadership potential and a desire to contribute to the profession of medicine as a physician or medical scientist. The colleagues Janelle interviews in this series offer unfiltered guidance and personal experiences on overcoming failure, handling the stressful college admissions process, and advice they would give to the high achieving students of America today to remain successful. In the interview series, Tam dives into several Princeton students lives, in different majors and graduation years. The diversity of these interviews ensures that leading students, no matter their desired career are privy to privileged information to help them succeed. Students can expect to see conducted interviews with; a current medical student enrolled in an Ivy-League M.D./Ph.D. program, a former Olympian, and a filmmaker. In the second video of the series, Tam sits down with Eric Hayes, a junior majoring in physics at Princeton with a passion for filmmaking. The two talk about his experience making his own film, how to combine things you are passionate about, and what it was like applying for colleges in the United States. Hayes gives students a better look into his love of science and filmmaking, “I'm passionate about stories, stories that get me excited about the world. Especially ones that give me a sense that the world is a much larger, more mysterious place than simply myself” Hayes said. Students can also expect to receive some advice on confidence and how important it is to achieve your goals. Hayes informs students, “I think part of it for me, has always been thinking about “what are your strengths”; of being honest with yourself and, when you've figured out what it is that you would like - or what it is that you think you're good at - not being afraid to give yourself credit to actually pursue those things". The National Leadership Academies support America’s high achieving high school students through career and focus-area programs and services. By creating the National Academy of Future Physicians and Medical Scientists and the National Academy of Future Scientists and Technologists, the National Leadership Academies are positioned to support students with the skills, motivation, guidance and mentorship they need to stay on track to achieve their goals.


There are two forms of the ADAR1 protein, ADAR1p110 and ADAR1p150. Several biological functions for ADAR1p150 have been revealed, but little is known about the role of ADAR1p110 in vivo. The new research shows that ADAR1p110 regulates the response of cells to certain stressors, including UV radiation, by protecting them from dying as a result of a process called apoptosis, a form of programmed cell death. "Before we started this work, we knew very little about the function of ADAR1p110 in vivo," said Kazuko Nishikura, Ph.D., professor in the Gene Expression and Regulation Program at The Wistar Institute and senior author of the study. "We knew that it could edit RNA, a polymeric molecule key for decoding the genetic material in a cell, but we did not know if this was important for its biological function." "We were surprised to find that ADAR1p110 has an important biological role as a stress-response protein, and that this function is independent of its ability to edit RNA," she added. To identify the functions of ADAR1p110, Nishikura and colleagues reasoned that the cellular location of the protein must be linked to its function. They found that when cells were exposed to stressors such as UV radiation, ADAR1p110 transiently moved from its normal location in the nucleoplasm and nucleoli of a cell into the cytoplasm. The researchers then characterized the pathway controlling this change in cellular distribution, finding that it involved a protein called MAP kinase p38, which was already known to have a role in regulating death or survival of stressed cells. Once in the cytoplasm, Nishikura and colleagues showed that ADAR1p110 protects a defined set of mRNAs from degradation. Many of these mRNAs decode genes involved in preventing apoptotic cell death, leading the researchers to conclude that ADAR1p110 protects cells from stress-induced apoptosis by protecting anti-apoptotic mRNAs from degradation. "Now that we have a well-defined function for ADAR1p110, we can work to understand its role in postnatal development and disease, in a particular cancer," added Nishikura. Explore further: It slices, it dices, it silences: ADAR1 as gene-silencing modular RNA multitool More information: Masayuki Sakurai et al, ADAR1 controls apoptosis of stressed cells by inhibiting Staufen1-mediated mRNA decay, Nature Structural & Molecular Biology (2017). DOI: 10.1038/nsmb.3403


News Article | May 6, 2017
Site: www.businesswire.com

AUSTIN, Texas--(BUSINESS WIRE)--Jonathan D. Leffert, MD, FACP, FACE, ECNU, was elected President of the American Association of Clinical Endocrinologists (AACE) at its 26th Annual Scientific & Clinical Congress in Austin, Texas, on Saturday, May 6. Dr. Leffert joined AACE in 1993, and after serving two consecutive terms on the Board of Directors, he was elected to the Executive Committee as Secretary in 2013. He has chaired many of the Association’s major committees, with a particular interest in the Legislative and Regulatory Committee. In 2016, Dr. Leffert served as Program Chair for the 25th Annual AACE Scientific & Clinical Congress in Orlando, Fla. As President of AACE, he will lead the world’s largest clinical endocrinology association with more than 7,500 members from more than 90 countries. “I am honored to serve as President of AACE, an organization recognized as a leader in clinical care, education and practice management in the field of endocrinology,” said Dr. Leffert. “I look forward to this opportunity to contribute to AACE’s continued growth and in promoting the interests of our patients and physicians in today’s sometimes volatile health care environment.” Dr. Leffert received his undergraduate degree from Brown University and his medical degree from the University of Minnesota Medical School. He completed his internship and residency in internal medicine at Parkland Memorial Hospital and the University of Texas (UT) Southwestern Medical Center in Dallas. He was subsequently awarded the AHA Bugher Fellowship in Molecular Biology to begin his research fellowship. In 1989, Dr. Leffert received a NIH Physician-Scientist Award for his work in cloning the rat amylin cDNa, and completed a clinical fellowship in Endocrinology, Diabetes and Metabolism at UT Southwestern in 1991. In private practice for 26 years, Dr. Leffert is the managing partner of North Texas Endocrine Center. He serves as the AACE Delegate to the American Medical Association (AMA) House of Delegates, and is a member of the American Board of Internal Medicine Subspecialty Board of Endocrinology, Diabetes and Metabolism. Board certified in Internal Medicine and Endocrinology, Diabetes and Metabolism, Dr. Leffert is a Fellow of the American College of Physicians (FACP), Fellow of the American College of Endocrinology (FACE) and has received Endocrine Certification in Neck Ultrasound (ECNU). About the American Association of Clinical Endocrinologists (AACE) The American Association of Clinical Endocrinologists (AACE) represents more than 7,500 endocrinologists in the United States and abroad. AACE is the largest association of clinical endocrinologists in the world. The majority of AACE members are certified in endocrinology, diabetes and metabolism and concentrate on the treatment of patients with endocrine and metabolic disorders including diabetes, thyroid disorders, osteoporosis, growth hormone deficiency, cholesterol disorders, hypertension and obesity. www.aace.com About the American College of Endocrinology (ACE) The American College of Endocrinology (ACE) is the educational and scientific arm of the American Association of Clinical Endocrinologists (AACE). ACE is the leader in advancing the care and prevention of endocrine and metabolic disorders by: providing professional education and reliable public health information; recognizing excellence in education, research and service; promoting clinical research and defining the future of Clinical Endocrinology. www.aace.com/college.


News Article | May 4, 2017
Site: www.eurekalert.org

Biologists from UNIGE have discovered how this organ adapts to the cycles of feeding and fasting, and the alternation of day and night In mammals, the liver plays a pivotal role in metabolism and the elimination of toxins, and reaches its maximum efficiency when they are active and feed. Biologists from the University of Geneva (UNIGE), Switzerland, have discovered how this organ adapts to the cycles of feeding and fasting, and the alternation of day and night within 24 hours. The researchers showed in mice that the size of the liver increases by almost half before returning to its initial dimensions, according to the phases of activity and rest. Published in the journal Cell, their study describes the cellular mechanisms of this fluctuation, which disappears when the normal biological rhythm is reversed. The disruption of our circadian clock due to professional constraints or private habits therefore probably has important repercussions on our liver functions. Mammals have adapted to diurnal and nocturnal rhythms using a central clock located in the brain. The latter, which is resettled every day by the light, synchronizes the subordinate clocks present in most of our cells. In the liver, more than 350 genes involved in metabolism and detoxification are expressed in a circadian fashion, with a biological rhythm of 24 hours. "Many of them are also influenced by the rhythm of food intake and physical activity, and we wanted to understand how the liver adapts to these fluctuations", says Ueli Schibler, professor emeritus at the Department of Molecular Biology of the UNIGE Faculty of Science. The liver oscillates, but not the other organs The mice forage and feed at night, while the day is spent resting. "In rodents following a usual circadian rhythm, we observed that the liver gradually increases during the active phase to reach a peak of more than 40% at the end of the night, and that it returns to its initial size during the day", notes Flore Sinturel, researcher of the Geneva group and first author of the study. The cellular mechanisms of this adaptation were discovered in collaboration with scientists from the Nestlé Institute of Health Sciences (NIHS) and the University of Lausanne (UNIL) in Switzerland. Researchers have shown that the size of liver cells and their protein content oscillate in a daily manner. The number of ribosomes, the organelles responsible for producing the proteins required for the various functions of the liver, fluctuates together with the size of the cell. "The latter adapts the production and assembly of new ribosomes to ensure a peak of protein production during the night. The components of ribosomes produced in excess are then identified, labeled, and degraded during the resting phase", explains Flore Sinturel. The amplitude of the variations observed by the biologists depends on the cycles of feeding and fasting, as well as diurnal and nocturnal phases. Indeed, the fluctuations disappear when the phases of feeding no longer correspond to the biological clock, which evolved in the course of hundreds of millions of years: "the size of the liver and the hepatocytes, as well as their contents in ribosomes and proteins, remain nearly stable when mice are fed during the day. Yet, these animals ingest similar amounts of food, irrespective of whether they are fed during the night or during the day", points out Frédéric Gachon of the NIHS, who co-directed the study. Many human subjects no longer live according to the rhythm of their circadian clock, due to night work hours, alternating schedules or frequent international travels. A previous study (Leung et al., Journal of Hepatology, 1986) determining the volume of the human liver during six hours using methods based on ultrasound, suggests that this organ also oscillates within us. If mechanisms similar to those found in mice exist in humans, which is likely to be the case, the deregulation of our biological rhythms would have a considerable influence on hepatic functions.

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