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Physiology

ZOLL Foundation Announces Grantees for its September 30, 2019 Funding Round – Business Wire

CHELMSFORD, Mass.--(BUSINESS WIRE)--ZOLL Foundation grants to young investigators in the fields of resuscitation and acute critical care totaled more than $676,000 in calendar year 2019. The September 30, 2019 round awarded $86,000 more than the round ending March 31, 2019; $381,000 vs. $295,000, respectively. Each round had nine awardees, for a total of 18 recipients receiving an average grant of $37,555 each. The next submission deadline is March 31, 2020.

It has been rewarding to assess applications to the ZOLL Foundation over the past five years, says Norman A. Paradis, MD, Professor of Medicine, Geisel School of Medicine at Dartmouth College, and a Director of the ZOLL Foundation since its inception in 2013. The caliber of young investigators looking to the Foundation to help them jumpstart their careers with seed funding, as well as the novel and challenging work they propose undertaking, is very encouraging indeed. Judging from the number and quality of applicants from diverse geographies each round, the Foundation is clearly now a known source of support with an important place in the future of resuscitation and acute critical care research.

Six of the nine recipients of grants for the round ending September 30, 2019 are with U.S.-based institutions, with others from Canada, France, and Bosnia and Herzegovina. Research these new investigators will be pursuing, usually with guidance from an established mentor, ranges from hemodynamic and metabolic interventions during cardiac arrest; sex hormone differences in cardiac arrest patients; and endothelial dysfunction and repair during septic shock; to using machine learning algorithms with physiology-guided resuscitation; and testing the impact of intra-shift naps during night shifts among EMS clinicians. For a complete list of research projects, researchers and their institutions, go to http://zollfoundation.org/projects.html.

Application guidelines and a streamlined application form for the March 31 deadline can be found at http://zollfoundation.org/apply.html.

About the ZOLL Foundation

The ZOLL Foundation is a 501 (c)(3) non-profit organization that operates independently from ZOLL Medical Corporation. It provides grants that support research and educational methods designed to improve resuscitation practices, prevent patient deterioration associated with cardiac arrest, and enhance the care of acute patients to reduce mortality and morbidity. Its focus is on providing seed grants for new investigators starting on the path of resuscitation and acute critical care research. More information on the Foundation, grantees to date, and the grant application process can be found at http://www.zollfoundation.org.

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ZOLL Foundation Announces Grantees for its September 30, 2019 Funding Round - Business Wire

Physiology

Keck Foundation gives $1 million to WSU researchers studying how sleep affects the brain – WSU News

By Josh Babcock, College of Veterinary Medicine

Cant sleep? Cant think clearly? Feel depressed? It may not be what you think.

The bacteria residing inside of you outnumber your own cells 10:1 and affect sleep, cognition, mood, brain temperature, appetite, and many additional brain functions. Yet we lack an understanding of how they do it, explained James Krueger, PhD, MDHC, Regents Professor at the WSU College of Veterinary Medicine, Department of Integrative Physiology and Neuroscience.

With a $1 million grant from the W. M. Keck Foundation, Krueger and colleagues at Washington State University and the University of Massachusetts Amherst (UMA) will explore whether variations in brain levels of bacterial fragments can account for lifes sleep/wake and 24-hour cycles, known as circadian rhythms.

The sleep research is led by Krueger and the circadian rhythm portion of the project is led by Associate Professor Ilia Karatsoreos, PhD, at UMA, who was formerly at WSU and a co-investigator on the study.

The award builds on nearly 40 years of cutting-edge sleep research. In the early 1980s, Krueger isolated a sleep-promoting molecule from brains of sleep deprived rabbits and from human urine. Its chemical structure was a muramyl peptide a building block component of bacterial cell walls.

At the time of the discovery, it was difficult to measure small amounts of muramyl peptides. As a result, determination of the brains muramyl peptide levels and whether they correlated with sleep-wake cycles or with circadian rhythms was shelved. Now, improved measurement technologies and the W. M. Keck Foundation funding enables this work to be done.

Further, WSU researchers will determine if sleep loss results in increased levels of muramyl peptides in the brain; a predicted result based on the 1980s work.

The UMA researchers will use models of simulated jet lag, a way to transiently disrupt our circadian (daily) rhythms. Disruption of these rhythms is associated with multiple changes including sleep, cognition, and body temperature. They will determine if muramyl peptide levels in the brain correlate with such changes.

When jetlagged, many of the normal bodily functions are out of synchrony with each other. This is a consequence of altering circadian rhythms, Karatsoreos said. By looking for changes of bacterial products in the brain, we anticipate we will discover new approaches to treat jet lag, and possibly the desynchrony of physiological functions that occurs with old age.

A third goal of the W. M. Keck funded work will be to determine how brain muramyl peptides elicit sleep. Our minds are an outcome of a bacteria/human symbiosis, Krueger said. Expanding this concept by determination of how such disparate species talk to each other will transform our views of cognition, psychiatric disorders, consciousness including sleep, and our understanding of what it means to be human.

Based in Los Angeles, the W. M. Keck Foundation was established in 1954 by the late W. M. Keck, founder of the Superior Oil Company. The Foundations grant making is focused primarily on pioneering efforts in the areas of medical research, science and engineering and undergraduate education. The Foundation also maintains a Southern California Grant Program that provides support for the Los Angeles community, with a special emphasis on children and youth. For more information, please visit www. wmkeck.org.

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Keck Foundation gives $1 million to WSU researchers studying how sleep affects the brain - WSU News

Physiology

Students share their favorite films of the 2010s Queen and Slim, Call Me By Your Name among those listed – The Aggie

Other favorites include Disobedience, Shutter Island, The Martian

This decade brought extraordinary films that left their mark on the history of cinema. Disney saw major success with the release of both Frozen and Frozen 2, as well as the highly anticipated sequel to The Incredibles. The Marvel cinematic universe finished the decade with multiple Avengers movies, ending one chapter and allowing a new one to begin in the new decade. These blockbuster films have made their mark on viewers, but there are other films that made a more personal impact on UC Davis students.

A number of students took the time to share their favorite pieces of cinema from this decade with The California Aggie.

Minh Tran, a first-year biopsychology major, said her film of the decade was Silenced, directed by Hwang Dong-hyuk.

The film was an advocate for sexual assault victims, [and it] calls out the predator and toxic power dynamic in work environment, Tran said.

Caroline Hopkins, a first-year undeclared major, said Disobedience, directed by Sebastian Lelio, is a deeply emotional and cutting tale of self-discovery.

Neha Singh, a third-year neurobiology, physiology and behavior major, said Wonder Woman, directed by Patty Jenkins, was the film that stood out to her this decade because it was empowering and very funny.

Husnaa Formoli, a third-year neurobiology, physiology and behavior major, said her favorite film was Shutter Island directed by Martin Scorsese.

I love movies that are unpredictable, and this movie was unpredictable with a twist at the end, Formoli said. The acting was phenomenal.

Ariel Guzman-Avila, a third-year international relations major, expressed his opinion on The Martian directed by Ridley Scott.

The film demonstrated unity and genuine cooperation throughout the entire film involving many parties who always are at odds, Guzman-Avila said. I was most impacted understanding that I too would wish to see global cooperation such as that of NASA and China or a new space colonization effort with my lifetime.

Est Banuelos, a third-year political science major, named Queen and Slim, directed by Melina Matsoukas, as her favorite film this decade.

It impacted me the most because it allows its viewers to grasp a closer sense to what we are currently facing today in America, Banuelos said. The door to higher levels of racism opened up with the current president we have.

Madison Satre, a fourth-year psychology major, was moved by Call Me by Your Name, directed by Luca Guadagnino.

It reinforced living in the moment and taking chances when you can, because you never know when the moment will pass, Satre said.

Shreya Kandasamy, a fourth-year psychology and Chicana/o studies double major noted that Before Midnight, directed by Richard Linklater, taught [her] how relationships are not perfect and that communication is key to sustaining relationships.

Noemi Gregorio, a third-year communications major, said World War Z, directed by Marc Forster, made an impact on her.

I thought it was crazy because it was something I had never seen before, Gregorio said. If you see the movie you will literally see the world collapsing in front of you. It was just a movie, but [it] felt possible.

Alisha Singh, a third-year political science and public service major, said the film that resonated with me the most was Alita: Battle Angel, directed by Robert Rodriguez.

It taught meaningful lessons about the strength of grit and never giving up.

Written by: Gabriela Hernandez arts@theaggie.org

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Students share their favorite films of the 2010s Queen and Slim, Call Me By Your Name among those listed - The Aggie

Immunology

Kymera Therapeutics to Present Preclinical Data on its First-in-Class Selective and Potent Oral IRAK4 Degraders in Cutaneous Inflammation – Yahoo…

Company names first inflammation/immunology disease indication: Hidradenitis suppurativa

CAMBRIDGE, Mass., Feb. 5, 2020 /PRNewswire/ --Kymera Therapeutics Inc., a biotechnology company pioneering targeted protein degradation to discover breakthrough medicines for patients, today announced the company will present preclinical data demonstrating that oral daily dosing of its IRAK4 degraders completely suppressed IRAK4 protein expression in skin and immune cells and inhibited cutaneous inflammation. Data support the development of Kymera's degraders for chronic inflammatory and autoimmune diseases, including the company's first named inflammation/immunology disease indication, hidradenitis suppurativa (HS). Research will be presented at the 9th European Hidradenitis Suppurativa Foundation Scientific Conference in Athens, Greece on Feb. 6 at 10:30 AM GMT+2 in the Ilissos room of the Athens Caravel hotel (Abstract #86).

(PRNewsfoto/Kymera Therapeutics LLC)

IRAK4 is a protein known to play a significant role in inflammation mediated by the activation of toll-like receptors (TLRs) and IL-1 receptors (IL-1Rs). While TLR and IL-1R signaling via IRAK4 is involved in the normal immune response, aberrant activation of those pathways is the underlying cause of multiple inflammatory and autoimmune conditions, including HS, atopic dermatitis and rheumatoid arthritis.

"Our latest findings build on the data presented last year at the American College of Rheumatology (ACR) showing the ability of IRAK4 knockdown in skin and spleen to suppress cutaneous inflammation in mice," said Jared Gollob, MD, CMO of Kymera Therapeutics. "Importantly, we have also demonstrated that oral daily administration of an IRAK4 degrader leads to complete knockdown of IRAK4 in skin and immune cells in higher species that is well-tolerated. These findings support development in hidradenitis suppurativa, a chronic inflammatory skin disease where robust IRAK4 inhibition has the potential to block the painful, destructive neutrophilic and lymphocytic inflammation driven by chronic TLR and IL-1R activation."

Last November, at the ACR meeting in Atlanta, Kymera introduced its selective and potent oral IRAK4 degraders, showing in vitro inhibition of cytokine and chemokine induction by TLR agonists and IL-1bthat was superior to IRAK4 kinase inhibitors as well as suppression of neutrophil infiltration and IL-1bproduction in vivo in the mouse MSU air pouch model.

"Inhibition of the TLR/IL-1R pathway with a single oral small molecule targeted against IRAK4 has great potential for the treatment of devastating autoimmune and chronic inflammatory diseases like HS, where inflammation is caused by multiple different IL-1 family cytokines as well as TLR stimulation," said Nello Mainolfi, Founder, Presidentand CEO, Kymera Therapeutics. "It is encouraging to see that we can safely achieve the level of IRAK4 knockdown in relevant tissue necessary to treat a disease like HS which has a high inflammatory burden. We look forward to moving our lead compound into the clinic in healthy volunteers by the end of 2020."

EHSF Study Highlights ABSTRACT #86, "Identification of highly potent and selective Interleukin-1 receptor associated kinase 4 (IRAK4) degraders for the treatment of hidradenitis suppurativa," will be presented byVeronica Campbell, Principal Scientist at Kymera Therapeutics.

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New data showed:

About Kymera TherapeuticsKymera Therapeutics is a biotechnology company pioneering a transformative new approach to treating previously untreatable diseases. The company is advancing the field of targeted protein degradation, accessing the body's innate protein recycling machinery to degrade dysregulated, disease-causing proteins. Powered by Pegasus, a game-changing integrated degradation platform, Kymera is accelerating drug discovery with an unmatched ability to target and degrade the most intractable of proteins, and advance new treatment options for patients. For more information visit, http://www.kymeratx.com.

About PegasusPegasus is Kymera Therapeutics' proprietary protein degradation platform, created by its team of experienced drug hunters to improve the effectiveness of targeted protein degradation and generate a pipeline of novel therapeutics for previously undruggable diseases. The platform consists of informatics driven target identification, novel E3 ligases, proprietary ternary complex predictive modeling capabilities, and degradation tools.

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Kymera Therapeutics to Present Preclinical Data on its First-in-Class Selective and Potent Oral IRAK4 Degraders in Cutaneous Inflammation - Yahoo...

Immunology

3 Important Things to Know About Gilead Sciences’ Q4 Results – The Motley Fool

Gilead Sciences (NASDAQ:GILD) made headlines in recent days after the company announced that it was working with Chinese authorities to test its Ebola drug remdesivir in treating the deadly coronavirus strain that has become an epidemic. But that wasn't the biggest news for Gilead this week.

The big biotech reported its 2019 fourth-quarter and full-year results after the market closed on Tuesday. Here are three important things to know about Gilead's Q4 update.

Image source: Getty Images.

Gilead endured a long stretch where its revenue declined quarter after quarter. That wasn't the case in Q4, though. The company reported Q4 revenue of $5.9 billion, up from $5.8 billion in the prior-year period. This result even topped the consensus Wall Street revenue estimate of $5.71 billion.

Sure, Gilead's hepatitis C virus (HCV) franchise continued to weigh on the company's total revenue. HCV sales fell nearly 19% year over year in the fourth quarter to $630 million. But the quarter-over-quarter decline of only 6.5% wasn't too bad considering what Gilead has experienced in the past.

The biggest bright spot for Gilead yet again was its HIV franchise. HIV sales jumped 12% year over year in Q4 to $4.6 billion, with Biktarvy leading the way with sales of $1.57 billion. Although Descovy was the only other HIV drug in Gilead's lineup to deliver sales growth, the combination of it and Biktarvy were more than enough to offset declining sales for Truvada, Genvoya, and other HIV drugs.

Yescarta didn't pick up much momentum in Q4, though. Sales rose nearly 51% year over year in the fourth quarter to $122 million, but that was only slightly above the $118 million recorded in the third quarter.

While Gilead topped Wall Street's Q4 revenue estimate, it was a different story on the bottom line. The biotech posted adjusted earnings of $1.7 billion, or $1.30 per diluted share. This result was lower than the $1.9 billion, or $1.44 per diluted share, generated in the prior-year period. It was also well below the average analysts' Q4 earnings estimate of $1.67 per share.

Gilead's earnings based on generally accepted accounting principles (GAAP) looked much better, though. The company reported GAAP earnings of $2.7 billion, or $2.12 per share, up significantly from GAAP earnings of only $3 million in the prior-year period. However, this big improvement stemmed mainly from some positive tax effects from accounting moves related to asset transfers and net gains from equity securities.

Analysts probably weren't too bothered by Gilead's big adjusted earnings miss. It's possible that they didn't factor in some of the company's acquisition-related expenses.

Gilead provided what could be described as lackluster full-year 2020 guidance. The company projects product sales to be between $21.8 billion and $22 billion. The midpoint of that range is lower than the $22.1 billion in product sales generated in the full year 2019.

Non-GAAP adjusted earnings per share (EPS) for full-year 2020 are expected to be between $6.05 and $6.45. The midpoint of this range is well below the consensus Wall Street adjusted EPS estimate for 2020 of $7.01.

At first glance, it might also appear that Gilead's adjusted EPS will decline from its full-year 2019 level. However, beginning this year, the company isn't excluding stock-based compensation expense from its non-GAAP figures. On an apples-to-apples basis, Gilead's adjusted EPS outlook for 2020 reflects a year-over-year increase of 2% at the midpoint of the guidance range.

If I had to sum up Gilead's fourth-quarter results in one word, it would probably be "blah." There simply was nothing in the company's update to excite investors.

However, pipelines are more important to the prospects for biotech stocks than past quarterly results. Gilead could generate more excitement later this year if it wins FDA approval for immunology drug filgotinib in treating rheumatoid arthritis (RA). Some analysts think filgotinib could achieve peak annual sales in the ballpark of $6 billion if approved for RA and other targeted immunology indications.

Gilead also ended 2019 with cash, cash equivalents, and marketable debt securities totaling$25.8 billion. That's a big cash stockpile the company could use to bolster its pipeline. The company is also putting its ample cash flow to use in another way that should delight investors -- its dividend. Gilead announced an 8% dividend increase beginning in the first quarter of 2020.

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3 Important Things to Know About Gilead Sciences' Q4 Results - The Motley Fool

Immunology

It’s a Gut Reaction – Technology Networks

A new study has revealed how the guts protective mechanisms ramp up significantly with food intake, and at times of the day when mealtimes are anticipated based on regular eating habits.

Researchers from the Walter and Eliza Hall Institute found, in laboratory models, that eating sets off a hormonal chain reaction in the gut.

Eating causes a hormone called VIP to kickstart the activity of immune cells in response to potentially incoming pathogens or bad bacteria. The researchers also found that immunity increased at anticipated mealtimes indicating that maintaining regular eating patterns could be more important than previously thought.

With the rise in conditions associated with chronic inflammation in the gut, such as irritable bowel and Crohns disease, a better understanding of the early protective mechanisms governing gut health could help researchers to develop prevention strategies against unwanted inflammation and disease.

The research, led by Professor Gabrielle Belz and Dr Cyril Seillet from the Walter and Eliza Hall Institute, was published in the journal Nature Immunology.

- Eating activates immune cells in the gut that protect against pathogens and preserve gut health.

- Immunity in the gut also ramps up at regular mealtimes in anticipation of eating and a potentially increased risk of infection.

- Understanding the complex interactions between eating, gut health and inflammation could aid in the development of prevention and treatment strategies for chronic inflammatory diseases.

So how does it work?

When food is consumed nerves in the intestine produce a hormone called vasoactive intestinal peptide (VIP) to switch on a protective response in the gut.

Professor Belz said the team showed, for the first time, that food-induced activation of VIP in preclinical models was vital for a subset of immune cells called ILC3s to mount a protective response in the gut.

Food intake switches on VIP, which plays a critical role in alerting the guts army of ILC3 immune cells. In response, ILC3s secrete interleukin-22 (IL-22), which swings into protective action to defend against pathogens and maintain tissue integrity.

We also showed that a deficiency in VIP limits the production of IL-22, which in turn negatively impacts the immune systems ability to prevent unwanted inflammation, she said.

The researchers used advanced imaging techniques to identify the players integral to protective immunity in the gut. Using a new imaging technique that makes tissue translucent, the researchers were able to capture high-resolution, 3D images of how VIP and ILC3 immune cells interact to protect the gut. Results showed their close proximity which confirmed their interdependence.

The researchers also showed that circadian clock genes could enable the gut to ramp up immunity in anticipation of regular mealtimes.

Dr Seillet said baseline gut immunity fluctuated throughout the day, based on circadian rhythms and an anticipatory response to regular eating patterns.

We saw that gut immunity not only spikes with food intake. It also rises and falls due to inbuilt cellular machinery regulated by the circadian clock gene Bmal1, which appears to activate immune cells when eating is likely, Dr Seillet said.

While more work needs to be done to better understand this anticipatory mechanism, the results are very interesting and could help to explain why disruptions to circadian rhythms and regular eating patterns could increase chronic inflammation in the gut.

Dr Seillet said a detailed knowledge about mechanisms for gut protection and tissue repair could be useful for preventing against early-stage gut inflammation, before full-blown disease occurred.

The next steps of our research include gaining a molecular understanding of what properties of food are responsible for kickstarting the process of protective immunity, he said.

For example, are there certain diets that drive a more protective response than others?

ReferenceThe neuropeptide VIP confers anticipatory mucosal immunity by regulating ILC3 activity. Cyril Seillet et al. Nature Immunology volume 21, pages168177(2020),https://doi.org/10.1038/s41590-019-0567-y.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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It's a Gut Reaction - Technology Networks

Immunology

Kineta Invited to Participate at the BIO CEO & Investor Conference – BioSpace

SEATTLE, Feb. 5, 2020 /PRNewswire/ --Kineta Immuno-Oncology., a clinical stage biotechnology company focused on the development of novel immunotherapies in oncology, neuroscience and biodefense announced today that Kineta's management team has been invited to participate at the BIO CEO & Investor Conference. Craig W. Philips, President, will provide a corporate overview at the conference which is being held February 10-11 at the Marriott Marquis in New York. Now in its 22nd year, the BIO CEO & Investor Conference is one of the largest independent investor conferences focused on established and emerging publicly traded and select private biotech companies.

Presentation DetailsDate: Tuesday, February 11thTime: 10:00 AM, Eastern TimeLocation: New York Marriott Marquis

Kineta, Inc. is a clinical stage biotechnology company committed to developing disruptive life science technologies that address unmet patient needs. We have leveraged our expertise in innate immunity and immunology to advance a focused pipeline of investigational drugs in oncology, neuroscience and biodefense. We actively collaborate with a broad array of private, government and industry partners to advance our innovative products. For more information on Kineta visit our website, http://www.kinetabio.com, follow us on Twitter at @kinetabio, LinkedIn and Like us on facebook.com/KinetaBio.

NOTICE: This document contains certain forward-looking statements, including without limitation statements regarding Kineta's and its affiliates' plans for pre-clinical and clinical studies, regulatory filings, investor returns and anticipated drug effects in human subjects. You are cautioned that such forward-looking statements are not guarantees of future performance and involve risks and uncertainties inherent in Kineta's and its subsidiaries' businesses which could significantly affect expected results, including without limitation progress of drug development, ability to raise capital to fund drug development, clinical testing and regulatory approval, developments in raw material and personnel costs, and legislative, fiscal, and other regulatory measures. All forward-looking statements are qualified in their entirety by this cautionary statement, and neither Kineta nor its affiliates undertake any obligation to revise or update any forward-looking statement to reflect events or circumstances after the issuance of this press release.

Contact:Jacques Bouchy233729@email4pr.com(206) 378-0400

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Biochemistry

Biology / Biochemistry News from Medical News Today

2004-2020 Healthline Media UK Ltd, Brighton, UK, a Red Ventures Company. All rights reserved. MNT is the registered trade mark of Healthline Media. Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a healthcare professional.

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Biology / Biochemistry News from Medical News Today

Biochemistry

Department of Biochemistry School of Medicine

The graduate program in Biochemistry began in 1960 starting with the offering of Masters in Science (M.S.) and doctor in Philosophy (Ph.D.) degrees in Biochemistry and Nutrition. The name of the department was changed in 1992 to Department of Biochemistry. The graduates of our program can be found throughout the industrial, academic and government environment in Puerto Rico, the U.S. mainland and in Latin America. The department faculty actively seeks external funds to support our graduate students and have been able to improve our research facilities with state of the art instrumentation.

The Department of Biochemistry characterizes itself by conducting research in the following areas: Molecular and Genetic Alterations in Disease, Biochemistry of Proteins, Protein Structure/Function Relationships, Biochemistry of Glycoconjugates and Cellular Differentiation, Interactions between Nutrition and Disease, Aging and Oxidative Stress, Ocular Biochemistry, Clinical Biochemistry, Analytical Biochemistry, Biochemical and Molecular Toxicology, Biochemical Pharmacology and Molecular Biology. Individual faculty members also participate as mentors in the Intercampus Ph.D. program in Biology.

The graduate student of the Department of Biochemistry should be able to practice his/her profession in a research, academic or industrial environment either in Puerto Rico or at the International level. It is expected that the graduate of the Biochemistry department contribute to the economic, social and cultural development of Puerto Rico. In order to achieve these goals the mission of the graduate program in Biochemistry is to prepare professionals with the fundamental and essential knowledge in the discipline of Biochemistry. In a wider context, the mission of the Biochemistry program is to prepare professionals that will practice their profession with the firm purpose to advance basic and applied knowledge in the field of Biochemistry, through their professional and scholarly activities contributing in solving the daily health related problems of our society which results in human benefit. It is expected that the biochemistry graduate practice their profession with the highest ethical principles, proper of the discipline they have chosen and that they set a solemn example for the future generations.

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Department of Biochemistry School of Medicine