Monthly Archives: March 2022

Published in Molecular Psychiatry, a team of scientists from the University of Minnesota Medical School, University of Texas Health San Antonio, and the Biomedical Research Institute (BRI) of the Foundation for Research and Technology Hellas (FORTH) in Greece found that the disruption of a circadian clock gene may be involved in the development of autism spectrum disorder.

Autism spectrum disorder, or ASD, refers to a neurodevelopmental disorder characterized by a wide range of behavioral conditions including challenges with social skills, repetitive behaviors, speech and nonverbal communication. According to the Centers for Disease Control and Prevention, ASD affects one in 44 children in the U.S.

About 50-80% of children with ASD have sleep problems, compared to less than 30% in the general population. The causes of sleep problems in ASD are not entirely clear, but a malfunctioning body clock could be the culprit.

It has long been recognized that the function of the body clock is frequently disrupted in autism patients and these patients often exhibit various sleep problems, said Ruifeng Cao, MD, PhD, an assistant professor of neuroscience at the U of M Medical School, Duluth Campus and co-author of the study. But, it is not known whether clock gene disruption can directly cause autism.

The study found that the disruption of an essential clock gene in preclinical models can lead to autistic-like phenotypes. Specifically, the global or cerebellar deletion of the Bmal1 gene can cause severe impairments in sociability, social communication and excessive repetitive behaviors.

The models also illustrated damages to their cerebellum or cerebellar ataxia. The research team further studied the pathological changes in the cerebellum and found a number of cellular and molecular changes that indicate neurodevelopmental deficits.

Clock gene disruption could be a mechanism underlying several forms of autism and potentially other neurodevelopmental conditions, and this finding paves the way for further exciting research, said Christos Gkogkas, PhD, a lab principal investigator in neurobiology at BRI of FORTH.

The research team plans to continue to study other clock genes that are found mutated in ASD. More importantly, they recommend development of novel therapeutic strategies based on their findings.

The study is supported by grants from the National Institute of Health and the Winston and Maxine Wallin Neuroscience Discovery Fund.

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The research team consists of Drs. Harry Orr, Alfonso Araque, Paulo Kofuji, and Jonathan Gewirtz (now at Arizona State University) from the U of M Medical School; Dr. Victor Jin from UT Health San Antonio; and Dr. Christos Gkogkas from BRI-FORTH in Greece.

About the University of Minnesota Medical SchoolThe University of Minnesota Medical School is at the forefront of learning and discovery, transforming medical care and educating the next generation of physicians. Our graduates and faculty produce high-impact biomedical research and advance the practice of medicine. We acknowledge that the U of M Medical School, both the Twin Cities campus and Duluth campus, is located on traditional, ancestral and contemporary lands of the Dakota and the Ojibwe, and scores of other Indigenous people, and we affirm our commitment to tribal communities and their sovereignty as we seek to improve and strengthen our relations with tribal nations. For more information about the U of M Medical School, please visit med.umn.edu.

The Biomedical Research Institute of FORTHThe Biomedical Research Institute (BRI) of FORTH at Ioannina consists of 18 research teams that comprise 140 members. The groups of BRI work in basic molecular and cellular biology areas of biomedical research with high interest in public health and biomedicine, such as vascular biology, stem cell biology and regenerative medicine, cancer biology, neurobiology, and biomedical technology.

The Foundation for Research and Technology - Hellas (FORTH) is one of the largest research centers in Greece, comprising nine Research Institutes. FORTH conducts specialized scientific research in strategic high-added value sectors, focusing on interdisciplinary research and development (R&D) activities in areas of major scientific, societal and economic interest.

Molecular Psychiatry

Observational study

Animals

Autistic-like behavior and cerebellar dysfunction in Bmal1 mutant mice ameliorated by mTORC1 inhibition

17-Mar-2022

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Research Brief: Clock gene mutation found to contribute to the development of autism - EurekAlert

by Dr. Paras Singh

How is the Indian government fairing on the TB front? Tuberculosis is a critical health issue in our country. The WHO stated that India has the maximum number of TB cases in the world. A quarter of the global TB cases reside in India. As per the global TB report 2020 2,640,000 TB incidents were recorded within India, making us have the highest numbers of both TB and MDR TB.

In 2020, the Indian government stated that they aim to eliminate the disease by 2025 with the help of its National TB Elimination Program. This programs interventions are majorly around investments in healthcare and a tie-up of the government and the private medical infrastructure.

However only 10% of the people are having DRTB and all these prior efforts have yielded inadequate declines, and will not accelerate the progress towards ending TB. New, innovative diagnostic tools and smarter interventions can accelerate progress towards TB elimination. The lack of proper, affordable and accessible diagnostic tools has led people to settle for delayed or sub-optimal treatments while missing to cover a large number of patients.

Diagnostic molecular technology approved by WHO can play an effective moving towards TB elimination that has been integrated into the four strategic pillars of GOI mandate Detect Treat Prevent Build (DTPB).

Moreover, TB co-morbidities like Diabetes, HIV and tobacco-related problems have also been prioritised, and as close to 1 lakh patients with TB/HIV were put on a daily DOT routine around 5 lakh people were treated with preventive TB therapy. These interventions and strategies helped in lowering down TB fatalities by 82%.

DBT or Direct Benefit Transfer is a major reformation by the government, necessitating benefits targeted provisions of benefits to the patients through efficient technology usage. NIKSHAY, an online web-based and case-based application have been useful to give targeted deliveries to the citizens. The app makes the TB patients digitized database available and accessible nationally.

This app is further equipped to store bank details and other necessary information for DBT execution. The database is supported with PFMS also known as, Public Finance Management System for smoother benefits transfer into the beneficiaries accounts.

Many novel and innovative tools have been introduced by the collaborative effort of the government and the medical infrastructure. Wider usage of ICT tools and application health financing methodologies assures a rapid and accurate response while treating TB as an epidemic.

Another aspect that needs to be highlighted is the tie-up of the public and the private medical sector. RNTCP has ensured that the private laboratories provide an affordable service delivery under the revised NGO-PP schemes. This approach has brought together all the diagnostic tools LPA, CBNAAT, liquid culture DST under the single initiative called Promoting Affordable and Quality TB Tests. Also, the ICT-supported tools have helped in getting universal access to TB care. Getting notification from the private sector to the public sector. Response of public healthcare sector to all the people suffering from TB notified via private sector will come under the responsibility of public healthcare system. Patients support services like, adherence, comorbidity detection, drug susceptibility testing, infection prevention and social welfare support would be extended to the private healthcare facilities as well.

Periodic monitoring and upscaling high sensitivity diagnostic tests and algorithms. Improving the private service providers engagement will increase the affordability and accessibility of the diagnostic tools. Monitoring and supervision are non-negotiable in ensuring the achievement of the vision of TB Free India by 2025.

Dr. Paras Singh, Head & Specialist, Dept. of Molecular Medicine, National Institute of Tuberculosis and Respiratory Diseases, New Delhi

(DISCLAIMER: The views expressed are solely of the author and ETHealthworld does not necessarily subscribe to it. ETHealthworld.com shall not be responsible for any damage caused to any person / organisation directly or indirectly.)

Excerpt from:
How India is poised to eradicate TB with effective, accessible and affordable Diagnostic tools - ETHealthWorld

How much does a molecule weigh? Well, that depends.Molecules, like people, come in various shapes and sizes.

That difference in size can mean a lot for researchers in the ever-evolvingpharmaceutical industry. Molecular weight is a key component tomanufacturing it can actually be used to determine how effective a pharmaceutical drug is.

"Probably the single most important piece of information that you can get (from a mass) isits molecular weight How big is it? How heavy is it? Mass spectrometry is a very accurate way of measuring the masses of molecules," distinguished IU professor Martin Jarrold said.

Jarrold andfellow IU chemistry professorDavid Clemmer are the founders ofMegadalton Solutions, a start-up company whosetechnology has made a big splash in the measurement field.

Look inside: Monroe County's most expensive home sold in 2021 features lake view, lots of space

These two Indiana University chemistry professors developed a new, refined method to test the effectiveness of experimental pharmaceuticals. Some of these drugs, coined thenext-generation medicine, are projected to revolutionize the medical field.

"(The technology)just came along at the right time,"Jarrold told the Herald-Times.

Megadalton Solutions recently entered an exclusive licensing agreement withWaters Corporation, ananalytical laboratory instrument and software company. Waters was recently recognized as one of America's largest companies of 2021 by Fortune Magazine.

The technology, an IU-refinedtake on charge detection mass spectrometry (CDMS), will be usedto test the potency of newpharmaceutical drugs in the rapidly evolving field of gene-based therapies. This new wave of medicine can potentially prevent orprovide long-term treatment of certain genetic disorders.

Mass spectrometry converts the molecule into an ion, which can then be weighed on an instrument.

You might not recognize amass spectrometeroffhand, but you've definitely used one before if you've boarded a flight in the last 20 years. An airport'sdetector sensors are compact mass spectrometry instruments.These sensors are used as homeland security checks to identifyillegal drugs orexplosive compounds.

However, since the first mass spectrometer was invented in1912, the instrument has had limitations.

For objects with a light molecular weight, such as antibodies,scientists havea tried and true method of measurement known as conventional mass spectrometry. But for determining the weightof large, heavy molecules, it has historically been less like reading a number off a scale and more like that age-old weight guessing game typically seen at a county fair.These specific drugs, such as those being developed for gene therapy, can weigh over a million mass units.

"Whereas conventional mass spectrometry played a role in the development of the small-molecule drugs, it ran into this sort of fundamental problem with being able to measure the masses of the heavier, larger molecules that are being developed as drugs now," Jarrold said.

More IU news: Indiana University trustees violated open door law with Michael McRobbie payment approval

For heavier molecules, scientists must use charge detection mass spectrometry. Jarrold and his team of collaboratorshave builta machine thatcan analyzelarge, complex molecules with an unprecedented level of accuracy and speed.

According to Jarrold, the idea for the technology was borne out of a desire for kinship.

When he first arrived at IU, Jarrold felt like an outsider. While his colleagues were discussing their work withviruses, his background was rootedin massspectrometry.

"I thought, 'Gosh, you know, wouldn't it be cool if we could start weighing viruses and I'd have all these collaborators that I could work with and feel as thoughI was a member, instead of somebody on the outside,'" Jarrold recalled.

This led him to a scientific discovery, aided by several colleagues and students throughout the years.

According to Jarrold, he has spent close to a decade on the technology, tinkering in the IU chemistry building. The machine has been viable for five years now and Jarrold and others at IU continue to refineit for commercial use.

IUs Innovation and Commercialization Office madeefforts to patent a lot of the technology that helped secure thecorporatepartnership. Dan McNerny, a technologycommercialization manager in the office, has worked with Jarrold for several years on the business side.

"I did not need to be sold on it," McNerny said.

Before his current position,McNerny was a researcher who hadlooked into manufacturing therapeutics, where something like Jarrold's technology would have made a big difference.

"Ultimately why my project failed is because we could never actually determine what was in the mixtures that we were creating. We would tryto find how heavy it was and the result was you'd get a blob back,"McNerny said.

The technology can have various applications in the medical industry, such as analyzing vaccines or lipoproteins incardiovascular diseases.

"There's awhole slew of these large objects, which have not previously been accessible to accurate mass measurements, that cannow be analyzed," Jarrold said. "The sort of drug that CDMS really is having an impact in the area is gene therapy, which is really sort of revolutionizing medicine at the moment."

Waters Corporationhas indicated that Megadalton Solutions' technology will be further developed foruse in gene therapies.

Gene therapyis a new medical approach that can treator even preventcertain diseases by correcting the underlying genetic problem, either throughreplacing a faulty gene or addinga new one.Gene therapy has the potential of being a new form of treatmentfor a wide range of diseases, such as cancer, cystic fibrosis, diabetes and AIDS.

"Many of these genetic diseases, which are like death sentences for people that have them, can now be fixed," Jarrold said.

Currently, gene therapy can only treatmonogenic disorders, whicharecaused by variation in a single gene. Some examples of monogenic disorders include sickle cell anemia, cystic fibrosis andHuntington's disease.

"In the future, you can anticipate that the multiple gene ones can also be fixed as time goes on," Jarrold said.

Jarrold estimates that there areover 200 new gene- and cell-based therapy drugscurrently in the development research pipeline.

During development, pharmaceutical manufacturersmust verify there are no errors in the final product. Empty capsules could reduce the drug's potency. In a worst case scenario, it could even lead toharmful mutated genes. That's why technology such as Jarrold's CDMS is crucial in these preliminary stages.

Jarrold said he plans to continue working with Waterson the technology to improveits accuracy and performance. Once fully developed, the machines could appear in laboratories around the world.

"This could really lead to new and unexpected discoveries because nobody's measured the masses of these very large things with very high resolution," Jarrold said. "That area itself is like a complete unknown as to what we might find there. There could be some very interesting science there."

Contact Rachel Smithat rksmith@heraldt.com or @RachelSmithNews on Twitter.

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Indiana University-developed tech could lead to a revolution in medicine. Here's how. - The Herald-Times

Amid a growing COVID-19 surge occurring overseas, there are renewed concerns among health officials in the United States that the spread of the highly transmissible omicron subvariant BA.2, combined with waning vaccine immunity and the decision to end masking recommendations, could cause the country to face yet another viral resurgence.

"What we're seeing in Europe, and particularly in the U.K., is something we really need to pay attention to because they are starting to see a reversal and a resurgence of cases," Dr. Anthony Fauci, chief medical adviser to the White House, told "GMA3" on Friday. "So even though our cases are continuing to come down, I would not be surprised if in the next couple of weeks ... that we might well see an increase in cases."

The Centers for Disease Control and Prevention estimate that 23.1% of new cases in the U.S. are BA.2. Studies estimate that BA.2 is between 30% and 80% more infectious than the original strain, and federal data shows its presence in the U.S. is nearly doubling every week.

There are already initial indicators that the nation may be on the brink of an uptick as the nation begins to see a plateau in infection and hospitalization rates, which were previously declining.

A syringe is prepared with the Pfizer COVID-19 vaccine at a vaccination clinic at the Keystone First Wellness Center in Chester, Pa., Dec. 15, 2021.

Earlier this week, wastewater data shared by the CDC revealed that between Feb. 24 and March 10, 37% of wastewater sites monitored by the CDC have seen an increase of 100% or more of the presence of the COVID-19 virus in their wastewater. Approximately 30% of these sites have seen an increase of 1,000% or more

Nationwide, new data shows that COVID-19-related hospitalizations appear to also be plateauing following weeks of steady decline. Over the last two months, hospitalization levels had been dramatically falling, but over the last week those daily declines have become steadily smaller.

Virus-related hospitalizations now stand at about 23,000 patients, according to federal data.

"You just got over a wave of the most transmissible #SARSCoV2 variant the world has seen, with the highest level of hospitalizations in the pandemic," Dr. Eric Topol, professor of molecular medicine at Scripps Research, said in a tweet on Thursday. "Now you are facing a variant [with] 30% more transmissibility, [without] mitigation measures, low [vaccination] coverage, and gutting funding."

CDC Director Dr. Rochelle Walensky said Thursday that she too anticipates there could be an increase in new virus cases in the U.S. as BA.2 spreads, warning that it is "certainly ... possible" that mask recommendations will have to be reimplemented.

"We want to make sure that people have an opportunity to relax their mitigation strategies when things are good, as they are right now," Walensky said during a panel discussion with the Bipartisan Policy Center.

A woman reads directions before giving her daughter a COVID-19 antigen rapid test at home in Washington, Jan. 9, 2022.

"But then, they should put that mask in a drawer, because if we have more cases that occur in the winter time, if we have more cases that occur because of a new variant, we want to make sure that people have the opportunity to take those masks off, so that we can re-implement them and protect people, should we need them again," she added.

Officials are closely monitoring the viral resurgence occurring overseas, Walensky said, and looking for clues as to what it might foreshadow for the crisis in the U.S.

However, overseas, similar to the previous omicron surge, there are hopeful signs that should there be a resurgence, intensive care units and morgues will not be as overwhelmed as in past surges. In the U.K., ICU capacity has yet to see a notable increase, which experts say could ultimately prevent a significant spike in virus-related deaths.

"Their intensive care bed usage is not going up, which means they're not seeing a blip up of severe disease," Fauci told ABC News' Brad Mielke on the podcast "Start Here," in an interview that aired Friday, adding that officials in the U.K. have not reported an increase in severity due to the BA.2 subvariant.

The best way to evade a significant surge will be to get vaccinated and boosted, Fauci said.

Earlier this week, the CDC released data showing that vaccines are still dramatically reducing the risk of hospitalization or dying from COVID-19.

A registered nurse steps out of an isolation room at the Dartmouth-Hitchcock Medical Center, in Lebanon, N.H., Jan. 3, 2022.

In January, unvaccinated adults were nine times more likely to die of COVID-19, compared to vaccinated individuals, and six times more likely to require hospitalization. Unvaccinated adults were about 21 times more likely to die of COVID-19 in January, and 12 times more likely to require hospitalization, compared to fully vaccinated and boosted adults.

Although breakthrough COVID-19 infections surged during the omicron wave in February, unvaccinated adults were still 2.8 times more likely to test positive for COVID-19 compared to fully vaccinated individuals, and 3.2 times more likely to test positive compared to fully vaccinated and boosted adults.

Experts say Americans must be flexible and willing to take on the future challenges that may present themselves as we move into the next phase of the pandemic.

"We're not done with this pandemic as much as we all wish. We are not," newly named White House COVID-19 coordinator Dr. Ashish Jha said during an appearance on "Good Morning America" Friday. "Whatever the pandemic throws at us, we have got to be ready for it."

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Fears of COVID-19 resurgence in the US grow as officials warn of potential upticks - ABC News

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Groundbreaking cancer research helps shed light on recently identified syndrome

Ayden Isaacs, 15, (middle) walks along the Mississippi River in St. Louis County with his mother, Jennifer Isaacs, and his father, Michael Isaacs. Ayden Isaacs was diagnosed with DNMT3A Overgrowth Syndrome in 2015 at Washington University School of Medicine in St. Louis. Children and young adults with the rare genetic disease may have physical and intellectual disabilities and an increased risk for blood cancers, including acute myeloid leukemia (AML). Aydens clinical samples have helped researchers learn more about his condition and AML.

In 2008, a team of scientists at Washington University School of Medicine in St. Louis became the first to decode the DNA of a patients cancer cells and trace the disease to its genetic roots. The patient, a woman in her 50s, suffered from acute myeloid leukemia (AML), an aggressive and often deadly cancer of the blood and bone marrow. The findings garnered the research team worldwide acclaim and paved the way for more personalized approaches for the treatment of cancer based on the clusters of mutations in patients tumors.

One of the most unusual mutations discovered in that patients AML cells was in the gene DNMT3A. The gene had never been linked to cancer, so the significance of the genes mutations was unknown. But it was a fascinating candidate gene to consider. DNMT3A was known to encode an enzyme that can methylate DNA at very specific places in the genome, a process that can change patterns of gene expression and that was known to be very important for normal development.

In the year that followed, the Washington University team sequenced the DNMT3A gene in 280 additional AML patients and found that it was indeed one of the most common initiating mutations for this disease and that mutations in one particular site, at the 882nd amino acid in the DNMT3A protein, was more common than all of the others. This hot spot for mutations suggested that something special was going on there, and further studies from the lab of Timothy J. Ley, MD, clarified what that something was. Ley, the universitys Lewis T. and Rosalind B. Apple Professor of Medicine and chief of the Section of Stem Cell Biology in the Division of Oncology, helped lead the first sequencing of the AML patients genome.

The mutations at amino acid 882 changed the way the protein normally interacted with itself to make a functional enzyme, and reduced the activity of the enzyme by about 80% essentially rendering it inactive. When Ley and his then-trainees David Russler-Germain, MD, PhD, and David Spencer, MD, PhD, looked at the DNA methylation patterns in AML samples with this mutation, they found a very distinct signature, with pinpoint areas of reduced DNA methylation at very specific regions of the genome in every patient who had the mutation.

This knowledge framed an essential chicken vs. egg question: Were these areas with reduced DNA methylation important for causing AML, or were they just a byproduct of cancer transformation? The only way to find out would be to get a sample of blood cells from a person with the same exact DNMT3A mutation but who did not have AML, to see whether the changes in DNA methylation were already there.

But there was no obvious way to find such a patient.

On a bright winter afternoon in 2015, serendipity graced the investigators and the families of a group of patients with a rare genetic syndrome that had been discovered the year before.

As Ley sat in his office mulling over the conundrum that was confounding the field, his phone rang.

The caller Shashikant Kulkarni, PhD, then-head of the Department of Pathology & Immunologys Cytogenetics and Molecular Pathology Laboratory bombarded Ley with a staccato of facts: A patient at St. Louis Childrens Hospital. A 9-year-old boy named Ayden, with a newly described genetic syndrome associated with a mutation in the DNMT3A gene but his blood counts were normal. And, Kulkarni noted, the boy and his parents had consented to donating his blood and tissue samples for research.

I couldnt believe it, Ley recalled.

Shortly after that conversation, Ley received a call from Marwan Shinawi, MD, a professor of pediatrics in the Department of Pediatrics Division of Genetics & Genomic Medicine. Shinawi had just diagnosed Ayden with DNMT3A Overgrowth Syndrome, also known as Tatton Brown Rahman Syndrome (TBRS), a syndrome first identified in 2014 by a pediatric geneticist in London, Kate Tatton-Brown. The condition can cause individuals to be taller than average, overweight and have a large head circumference and distinctive facial features. People with the disorder also may have intellectual disabilities, behavioral difficulties and decreased muscle tone.

In 2014, there were only 13 patients in the world with a known diagnosis of the syndrome.

Youre not going to believe this, Shinawi told Ley over the phone, but the patient has the R882H mutation that youve been studying, and his father works here in pathology.

It was truly incredible, Ley said. There were 13 known patients in the world who had this syndrome. None of them to date had the mutation at position 882 that was so strongly associated with AML. This created a remarkable opportunity to learn more about how DNMT3A mutations contributed to TBRS and how they initiated AML.

Leys prior research on the mutation and blood cancers also triggered concern for Ayden. I worried that Ayden and these other children might be at increased risk of leukemia, Ley said. I knew that it was essential to monitor Aydens health while determining whether there is an increased risk of leukemia for patients with this syndrome.

Thanks to Aydens contribution to scientific research as well as similar contributions from dozens of other families from around the world the Washington University Medical Campus is now a global beacon for patient care and research for TBRS. Now, the syndrome is known to affect about 250 children and young adults worldwide, according to the TBRS Community, a family-led rare-disease organization founded by Jill Kiernan. Her daughter, Aevary, was one of the first to be diagnosed with the syndrome, in 2014.

The nonprofit, which emphasizes advocacy, education and research, is collecting information from families in a clinical registry to study the genetics, development and health of children with DNMT3A Overgrowth Syndrome and of their families.

Dr. Ley has been amazing about talking directly to families whose children have DNMT3A variants, Kiernan said. He says, Well do what we can. Well coordinate with their team. Well tell them what we know and what we dont know. And he does. Its not only Dr. Ley, but everyone weve worked with at Washington University has a sincere interest in helping these children and their families.

The childrens blood and tissue samples continue to be studied in laboratories across the School of Medicine, from oncology and genomics to neuroscience and pediatrics. In conjunction with the studies of clinical samples, genetically modified mouse models are proving to be an important new tool for understanding how DNMT3A mutations work. Mouse and human genomes share common genes that typically function in the same way. Such similarities make mice ideal for simulating human disorders to study how a single mutation can cause all of the features of a complex disease like TBRS. Remarkably, when the amino acid 882 mutation is created in mouse germline cells that make eggs and sperm, the animals develop virtually all of the features of the human syndrome including the reductions in DNA methylation noted in the AML patients. They also have an increased likelihood of developing blood cancers, including AML. These findings were published last year in Nature Communications.

The key to understanding genetic conditions such as TBRS is having both clinical data and samples, as well as mouse models, explained the papers first author, Amanda M. Smith, PhD, a former researcher in Leys lab who led the development of the mouse model with the amino acid 882 mutation.

Harrison Gabel, PhD, an assistant professor in the Department of Neuroscience, has created additional DMNT3A mouse models and focused on how they affect brain function. Were looking at it from a molecular level, how genes get turned on and off, and how that affects development to drive the overgrowth, obesity and neurologic dysfunction that occur in the disorder, he said. The collaborative environment and resources at Washington University position us to attack this particular disorder from all sides. Dr. Ley and I are working side by side, studying the gene in blood cells and in the brain. Combining our efforts with Dr. Shinawi, who understands the clinical aspects of this disorder, and adding in the remarkable relationship with patients and their families, it all adds up to a powerful synergistic approach.

Gabel is a member of the TBRS Communitys scientific advisory committee, and Ley and Shinawi serve on the medical advisory board. This nonprofit recently secured a three-year, $600,000 grant from the Chan Zuckerberg Initiative. It is a total game changer for our little organization thats been fueled by parent volunteers, said Kerry Grens, the groups vice president and the Department of Neurosciences new marketing administrator. Her son Adrian was diagnosed with TBRS in 2019, when he was 3 years old.

Shortly after Adrian was born, Grens and her husband noticed their son was delayed on milestones such as holding up his head and sitting. He also had strabismus (crossed eyes) and a congenital heart defect. We saw a lot of doctors before we came to Washington University, underwent genetic sequencing and received an official diagnosis from Dr. Shinawi, Grens said. It can feel hopeless to have a child with an incurable rare disease, and volunteering with the organization gives me a chance to feel like Im making progress, making a difference. A lot still needs to be answered about this genetic mutation and the associated risks for other diseases such as leukemia.

Research led by Margaret Ferris, MD, PhD, an instructor of pediatrics at Washington University and an oncologist at St. Louis Childrens Hospital, recently confirmed the scientists initial concerns: Patients with TBRS are at an increased risk about 250 times more than the general population for blood cancers, including acute myeloid leukemia. The study was published in November in Blood, the journal of the American Society of Hematology.

This can be difficult news to tell the families, obviously, but its the truth, and they need the truth, said Ley, the studys senior author. Do we need to monitor these children for early signs of the development of leukemia? The answer is, clearly, yes, we do.

Aydens dad, Michael Isaacs, said the truth, no matter what it may be, gives him hope. Not knowing is the biggest burden, said Isaacs, director of informatics and of external affairs for the Department of Pathology & Immunology. Knowing, and having a diagnosis, help set expectations for what the future may look like, but most of all, it gives me hope. The research being done, the dedication of the parents, and the collaborations at Washington University all give me hope.

Washington University School of Medicines 1,700 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, and currently is No. 4 in research funding from the National Institutes of Health (NIH). Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Serendipity unites physicians, researchers, families to fight rare genetic disease in kids Washington University School of Medicine in St. Louis -...

PHOENIX, Ariz. March 22, 2022 Severe fatty liver disease is commonly associated with obesity, but according to a review of scientific literature conducted by researchers at Temple University and the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, there is a growing body of evidence suggesting that even normal weight individuals can contract this potentially life-threatening condition.

Why this occurs is poorly understood, though some of the suspected liver-disease risk-factors for lean individuals include diet, genetics, ethnicity, and even menopausal status for women, according to the scientific review published today in the journal Diabetology and Metabolic Syndrome.

Because fatty liver disease, in most cases, is a clinically silent condition, the absence of early signs and symptoms, coupled with normal laboratory and body measurements, blind clinicians to the presence of severe liver disease in normal weight individuals, said Johanna DiStefano, Ph.D., Professor in TGens Metabolic and Fibrotic Disease Program, and head of TGens Diabetes and Fibrotic Disease Unit.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver condition in the U.S., and may affect an estimated 24% of the global population. The incidence of NAFLD is climbing worldwide, making it a significant health threat. Its most severe form can progress to a condition called nonalcoholic steatohepatitis (NASH), which is characterized by liver inflammation and oftentimes fibrosis, and can lead to cirrhosis, cancer of the liver, and death. All are difficult to diagnose and treat.

Surprise finding for lean patients

One study showed that between the time they were initially diagnosed and follow-up examinations lean individuals with NAFLD were at greater risk for developing severe liver disease than those with higher body mass index (BMI).

This unexpected finding suggests that lean individuals experience a faster rate of fibrosis progression compared to those with higher BMI, Dr. DiStefano said.

While obesity is the strongest independent risk factor for NAFLD, even in cases of severe obesity some individuals do not develop severe liver disease, suggesting there may be genetic factors at work; some genes that promote liver disease, and others that are protective against the condition.

For example, one study of more than 900 lean Japanese participants showed a doubling of NAFLD risk among those who carried the well-studied PNPLA3 gene.

Also, women are at high risk of developing NAFLD following the menopausal transition, likely due to hormone-related metabolic changes resulting from the loss of protective estrogens and other factors, the review said.

No consensus on NAFLD screening

There is no global consensus for how to screen for NAFLD due to the uncertain evidence supporting diagnostic tests, treatment options, cost-effectiveness and the potential long-term benefits of screening. And for lean individuals, guidelines for NAFLD are even less clear:

The development and distribution of consistent screening and risk assessment guidelines will be critical to ensure optimal clinical management for all NAFLD patients, the review said.

Assessing NAFLD risk among lean individuals may depend on greater awareness of menopausal status, genetic factors, ethnicity especially among those of Asian Indian and Hispanic ancestry alcohol consumption, and dietary factors, including added sugars, refined carbohydrates, saturated fat and cholesterol. A major question is whether NAFLD in lean individuals represents a distinct disease requiring specific management, as suggested by many researchers, or is it a type of classical obesity-associated NAFLD that will respond to the current approach of weight loss, and the control of insulin resistance, high blood pressure, and excessive fat in blood?

Much more work is needed not only to address risk factors but also to promote greater awareness among practitioners about the potential health risks associated with NAFLD among lean individuals, said Glenn S. Gerhard, M.D., Chair of the Department of Medical Genetics and Molecular Biochemistry at the Lewis Katz School of Medicine at Temple University.

Early detection, combined with the appropriate steps to mitigate NAFLD through lifestyle modifications and clinical interventions, may effectively prevent the progression to NASH in lean individuals, said Dr. DiStefano, adding that inclusion of lean individuals in NAFLD-related clinical trials is critical to reducing NAFLD in this patient group.

The review NAFLD in normal weight individuals was funded by grants from the National Institutes of Health (NIH).

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About TGen, an affiliate of City of HopeTranslational Genomics Research Institute (TGen) is a Phoenix, Arizona-based nonprofit organization dedicated to conducting groundbreaking research with life-changing results. TGen is affiliated with City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases: CityofHope.org. This precision medicine affiliation enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen. TGen is focused on helping patients with neurological disorders, cancer, diabetes and infectious diseases through cutting-edge translational research (the process of rapidly moving research toward patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and complex rare diseases in adults and children.Working with collaborators in the scientific and medical communities worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. For more information, visit: tgen.org. Follow TGen onFacebook,LinkedInandTwitter @TGen.

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Diabetology & Metabolic Syndrome

Literature review

People

NAFLD in normal weight individuals

24-Mar-2022

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See original here:
TGen-Temple review suggests even normal weight individuals are susceptible to severe fatty liver disease - EurekAlert

The Board of Regents approved the following items at its March 24 meeting:

For the 2022-23 academic year, classes at UM-Flint will begin Aug. 29 and end with spring commencement April 30. The calendar was approved March 24 by the Board of Regents. Both fall and winter terms have 69 days. The fall term will end Dec. 9, and the winter term will begin Jan. 4. There are no conflicts with religious holidays. The academic calendar was developed following the universitys well-established academic calendar guidelines.

Margaret C. Levenstein, professor of information, School of Information, effective Aug. 29, 2022.

Andrew Murphy, professor of political science, LSA, Aug. 29, 2022.

Tiffany J. Braley, Holtom-Garrett Family Professor of Neurology, Medical School, effective March 1, 2022, through Aug. 31, 2027.

Xiuli Chao, Ralph L. Disney Collegiate Professor of Industrial and Operations Engineering, College of Engineering, effective March 1, 2022, throughFeb. 28, 2027.

Pingsha Dong, Robert F. Beck Collegiate Professor of Engineering, College of Engineering, effective March 1, 2022, through Feb. 28, 2027.

Michael Flynn, Fawwaz T. Ulaby Collegiate Professor of Electrical and Computer Engineering, College of Engineering, effective March 1, 2022, through Feb. 28, 2027.

Paul G. Gauger, Norman Thompson, M.D. Professor of Surgery, Medical School, effective March 1, 2022, through Aug. 31, 2027.

Kelly L. Harms, Lewis and Lillian Becker Professor of Dermatology, Medical School, effective April 1, 2022, through Aug. 31, 2027.

*Sharon R. Kardia, Millicent W. Higgins Collegiate Professor of Epidemiology, School of Public Health, effective April 1, 2022, through March 31, 2027.

*Daniel J. Klionsky, Alexander G. Ruthven Professor of Life Sciences, Life Sciences Institute, effective July 1, 2022, through June 30, 2027.

Purnima Kumar, William K. and Mary Anne Najjar Professor of Dentistry, School of Dentistry, effective May 1, 2022, through April 30, 2027.

*Priscilla Lindsay, Claribel Baird Halstead Collegiate Professor, School of Music, Theatre & Dance, effective Sept. 1, 2022, through Aug. 31, 2025.

Joaquim R.R.A. Martins, Pauline M. Sherman Collegiate Professor ofAerospace Engineering, College of Engineering, effective March 1, 2022, through Feb. 28, 2027.

*Laurie K. McCauley, William K. and Mary Anne Najjar Professor of Periodontics, School of Dentistry, effective April 1, 2022, through March 31, 2027.

Robert J. ORourke, William J. Fry Professor of Surgery, Medical School, effective March 1, 2022, throughAug. 31, 2027.

Tuija I. Pulkkinen, George R. Carignan Collegiate Professor of Climate and Space Sciences and Engineering, College of Engineering, effective March 1, 2022, through Feb. 28, 2027.

Hom-Lay Wang, Collegiate Professor of Periodontics, School of Dentistry, for a five-year renewable term, effective April 1, 2022, through March 31, 2027.

Xueding Wang, Jonathan Rubin Collegiate Professor of Biomedical Engineering, Medical School, effective March 1, 2022, through Aug. 31, 2027.

Xian-Zhong Shawn Xu, Bernard W. Agranoff Collegiate Professor in the Life Sciences, Medical School, effective March 1, 2022, through Aug. 31, 2027.

*Marc A. Zimmerman, Marshall H. Becker Collegiate Professor of Public Health, School of Public Health, effective April 1, 2022, through March 31, 2027.

Robin A. Beck, acting director, Museum of Anthropological Archaeology, LSA, effective July 1, 2022, throughJune 30, 2023.

Eric R. Fearon, associate dean for cancer programs, Medical School, effective March 1, 2022.

Michael Galaty, director, Museum of Anthropological Archaeology, LSA, effective July 1, 2023, through June 30, 2026.

Pauline Jones Luong, Edie N. Goldenberg Endowed Director of the Michigan in Washington Program, LSA, effective Aug. 29, 2022, through Aug. 31, 2027.

Laurie K. McCauley, provost and executive vice president for academic affairs, Office of the Provost and Executive Vice President for Academic Affairs, effective May 16, 2022.

*Ravi Pendse, vice president for information technology and chief information officer, Office of the President, effective July 1, 2023, through June 30, 2028.

Jacob S. Klein, James B. and Grace J. Nelson Visiting Professor of Philosophy, Department of Philosophy, LSA, effective Aug. 29, 2022, through Dec. 31, 2022.

Nancy Savoca, John H. Mitchell Visiting Professor in Media Entertainment, Department of Film, Television, and Media, LSA, effective Aug. 29, 2022, through Dec. 31, 2022.

Isis H. Settles, transfer of tenure to professor of psychology, with tenure, professor of Afroamerican and African studies, without tenure, and professor of womens and gender studies, without tenure, LSA, effective Aug. 29, 2022.

*Reappointments

Kevin B. Atkins, assistant research scientist in the Department of Internal Medicine,Division of Nephrology, Medical School, May 2, 2022.Atkins received his B.A. in 1981 from Western Maryland College and his M.S. in 1984 from the University of Maryland. He received his Ph.D. in molecular, cellular and developmental biology from Iowa State University in 1991. Atkins joined the University of Michigan in 1991 as a research associate II and was promotedto senior research associate in 1999. In 2006, he was promoted to research laboratory specialistsenior. He joined the faculty ranks as a research investigator in 2010 and was promoted to assistant research scientist in 2014. Atkins scholarly interests focus on vascular smooth muscle physiology, specifically tounderstand the relationship between diabetes, kidney disease and hypertension and vascular dysfunction. His research also focuses on changes in vascular responsiveness in models of Type 1 diabetes andatherogenic kidney disease. Atkins has 25 peer-reviewed publications in high-impact journals. His work has led to several Department of Defense,National Institutes of Health and industry grants. Atkins is a member of the American Heart Association and a journal reviewer for the American Journal of Physiology: Heart and Circulatory Physiology.

Romana Capek-Habekovic, senior lecturer and lecturer IV in Italian in LSA, Dec. 30, 2014.Capek-Habekovic earned a B.A. in Italian with a minor in comparative literature in 1972 from the University of Zagreb. She received an M.A. in Italian literaturein 1978 from Wayne State University, and earned her Ph.D. in Italian literature in 1983 from the University of Michigan. Capek-Habekovic was appointed a lecturer at U-M in 1984. She was promoted to lecturer III in 1990 and lecturer IV in 2012. In 1997, she became director of the Elementary Language Italian Program after having been coordinator from 1990-96.Capek-Habekovic also served as the interim director of the Elementary Language French Program from 2012-14. Capek-Habekovic taught undergraduatecourses and graduate classes in Italian language and pedagogy, and in contemporary Italianliterature, particularly on Italian theater, Italian cuisine as a cultural practice, and Italian multimedia. She is the author of Tommaso Landolfis Grotesque Images, Insieme. Review Grammar and Reader for Second Year Italianand several other language books and manuals to teach the Italian language.

James H. Ellis, William Martel Collegiate Professor of Radiology, professor ofradiology, and professor of urology in the Medical School, April 30, 2022.Ellis received his B.S. in mathematics with honors in 1973 and his M.D. cum laude in 1978, both from the University of Michigan. He was a resident in diagnosticradiology from 1978-82 and assistant professor of radiology from 1982-84 at Indiana Universitys School of Medicine. Ellis joined U-M as an assistant professor in 1984, was promoted to associate professor in 1989 and to professor in 1996. He was chief of the radiology service at the affiliatedAnn Arbor Veterans Administration Medical Center from 1984-87, the first division director of the newly created abdomen division in the Department of Radiology at University Hospital from1987-92 and clinical director of the radiology department from 1992-98. He was the inauguralassociate chair for information technology in the radiology department from 1998-2017. He authored or co-authored 179 peer-reviewed publications. Ellis is a fellow of theAmerican College of Radiology, the Society of Uroradiology and the Society of Abdominal Radiology. He received the Gold Medal from the Society ofAbdominal Radiology in 2020.

Mark A. Helvie, Trygve O. Gabrielsen Collegiate Professor of Radiology andprofessor of radiology in the Medical School, March 25, 2022.Helvie received his B.S. from Duke University in 1976 and his M.D from the University of North Carolina at Chapel Hill in 1980. At the University of Michigan, he completed an internal medicine residency in 1983, a radiology residency in 1986 and a cross-sectional fellowship in 1987. He joined U-M as a lecturer in 1987, was promoted to assistant professor in 1988, to associate professor in 1994 and to professor in 2000. Helvies academic career was concentrated in breast radiology. At Michigan Medicine, Helvie was director of the Division of Breast Imaging from 1992-2018 and director of the Residency Training Program from 1989-92. Helvie received the OutstandingClinician Award and was inducted into the Michigan Medicine League of Clinical Excellence, and received the Gold Medal from the Society of Breast Imaging. He served in a leadership position at the National Comprehensive Cancer NetworkBreast Cancer Screening and Diagnosis Section, was an executive board member of the Society of Breast Imaging and held editorial positions at several journals.Helvie is a fellow of the American College of Radiology and the Society ofBreast Imaging.

Roland Kwok, associate professor of obstetrics and gynecology and associateprofessor of biological chemistry in the Medical School, April30, 2022.Kwok received his B.Sc. degree from Chu Hai College in Hong Kong in 1982, hisM.Sc. degree from the University of Saskatchewan in Canada in 1985 and his Ph.D. from the University of Pittsburgh in 1991. He received postdoctoral training at the Oregon Health Sciences University. He joined U-M as an assistant professor in 1998 and was promoted to associate professor in 2006.Kwoks research focused on how post-translational modifications, such asacetylation and phosphorylation, of factors involved in cell death pathways would determine cell death in cancer cells. He has more than 40 peer-reviewed publications, and his research helped reveal new targets for drugs in cancer treatment. His work was supported by the National Institutes of Health, the Leukemia and Lymphoma Society and the American Cancer Society. He also was a reviewer for various scientific journals and a research grant reviewer for the Department ofDefense for more than 15 years.Kwoks most recent service was a three-year term as a member of the Academic Performance Committee and the Advisory Board on Intercollegiate Athletics.

See the article here:
Regents Roundup March 2022 | The University Record - The University Record