How the “Marsupial Sabertooth” Thylacosmilus Saw Its World; Study Describes How Extinct Hypercarnivore Likely Achieved 3D Vision Despite Wide-Set Eyes More Characteristic of a Herbivore Than a Predator

A new study investigates how an extinct, carnivorous marsupial relative with canines so large they extended across the top of its skull could hunt effectively despite having wide-set eyes, like a cow or a horse. The skulls of carnivores typically have forward-facing eye sockets, or orbits, which helps enable stereoscopic (3D) vision, a useful adaptation for judging the position of prey before pouncing. Scientists from the American Museum of Natural History and the Instituto Argentino de Nivología, Glaciología, y Ciencias Ambientales in Mendoza, Argentina, studied whether the “marsupial sabertooth” Thylacosmilus atrox could see in 3D at all. Their results were published on March 21, 2023 in Communications Biology. The open-access article is titled “Seeing Through the Eyes of the Sabertooth Thylacosmilus atrox (Metatheria, Sparassodonta).”

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Researchers Identify Key Source of T-Cell “Exhaustion”–Discovery May Open Way to Drugs That Can Prevent T-Cell Therapies from Losing Their Potency Over Time

Dr. Cigall Kadoch

Custom-made to attack cancer cells, CAR T-cell therapies have opened a new era in the treatment of human cancers, particularly, in hematologic malignancies. All too often, however, the CAR T cells display a frustrating trait inherited from the body’s own immune system cells: a drastic loss of cancer-fighting fervor known as “exhaustion.” Exhaustion is not only seen in cancer-fighting T cells but is also frequent in the setting of viral infections, such as human immunodeficiency virus (HIV), hepatitis B/C viruses (HBV, HCV) and COVID-19 (SARS-CoV-2). The lapse into listlessness has diminished the effectiveness of CAR T-cell therapies in some patients and prompted scientists to try to find its source.  In a new study, scientists at Dana-Farber Cancer Institute and NYU Grossman School of Medicine show the commanding role of a specialized group of proteins in the nuclei of our cells, called mSWI/SNF (or BAF) complexes, both in activating T cells to attack cancer and triggering exhaustion.

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Protein Engineers Navigate Toward More Targeted Therapeutics

More than a third of FDA-approved drugs work by targeting a G protein-coupled receptor, or GPCR. The human body has more than 800 types of GPCRs that provide cells with information about the external environment to calibrate responses. Drugs that either block or activate GPCRs are used to treat a wide range of diseases including hypertension, pain, and inflammation. Most drugs bind to the outside of the receptor, but this can result in adverse side effects because receptors often resemble one another. In a new study published in Nature, Sivaraj Sivaramakrishnan, PhD, a Professor in the College of Biological Sciences, along with graduate student Fred Sadler and co-authors Michael Ritt and Yatharth Sharma, uncovered the role of the third intracellular loop in the GPCR’s signaling mechanism, suggesting the possibility of a more targeted approach to drug discovery and a paradigm shift for new therapeutics. The open-access article is titled Autoregulation of GPCR Signalling Through the Third Intracellular Loop.”

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Losing Key Type of Pancreatic Cell May Contribute to Diabetes

Multiple types of beta cells produce insulin in the pancreas, helping to balance blood sugar levels. Losing a particularly productive type of beta cell may contribute to the development of diabetes, according to a new study by Weill Cornell Medicine investigators. In the study, published March 16, 2023 in Nature Cell Biology, Dr. James Lo, Associate Professor of Medicine at Weill Cornell Medicine, and colleagues measured gene expression in individual beta cells collected from mice to determine how many different types of beta cells exist in the pancreas. The team discovered four distinct beta cell types, including one that stood out. The cluster 1 group of beta cells produced more insulin than other beta cells and appeared better able to metabolize sugar. The study also showed that loss of this beta cell type might contribute to type 2 diabetes.  The article is titled “A Beta Cell Subset with Enhanced Insulin Secretion and Glucose Metabolism Is Reduced In Type 2 Diabetes.”           

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Researchers Highlight Nucleolar DNA Damage Response in Fight Against Cancer

Cancer, which affects millions every year, requires proteins to spread through the body. In a new strategy to beat the wide-ranging disease, scientists are sabotaging its protein factories. In a new forum paper published on March 16, 2023 in Trends in Biology, researchers from the University of North Carolina at Charlotte encapsulated the young field of nucleolar DNA damage response (DDR) pathways. The review highlights six mechanisms by which cells repair DNA damage, including one which was published five months ago in Nucleic Acids Research by the same authors. By attacking these mechanisms, future applied researchers might be able to trip up cancer’s reproduction and growth. “The whole purpose of the Trends paper is to bring attention to scientists in the field and trigger their research,” says Shan Yan, PhD, the main author. “I did not realize the significance of this field, which is only fifteen years old, until a couple of years ago.” The review is titled “Molecular Mechanisms of Nucleolar DNA Damage Checkpoint Response.”

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Senescence-Associated Exosomes Transfer Fibrosis to Neighboring Cells

“This shows that SA-EXOs can serve as potent SASP mediators that activate invasive characteristics in neighboring cells.

A new research paper was published March 15, 2023 inAging (listed by MEDLINE/PubMed as “Aging (Albany NY)” and “Aging-US” by Web of Science) Volume 15, Issue 5, entitled, “Senescence-Associated Exosomes Transfer miRNA-Induced Fibrosis to Neighboring Cells.”

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Extra X Chromosome-Linked Gene May Explain Decreased Viral Infection Severity in Females

It has long been known that viral infections can be more severe in males than females, but the question as to why has remained a mystery – until possibly now. The key may lie in an epigenetic regulator that boosts the activity of specialized anti-viral immune cells known as natural killer (NK) cells. In a study published March 16, 2023 in Nature Immunology, a collaborative team of UCLA researchers has found that female mouse and human NK cells have an extra copy of an X chromosome-linked gene called UTX. UTX acts as an epigenetic regulator to boost NK cell anti-viral function, while repressing NK cell numbers.

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Genetic Causes of Three Previously Unexplained Rare Diseases Identified; Computational Approach Developed By Mount Sinai Researchers Helps Identify Previously Unknown Genetic Causes of Primary Lymphedema, Thoracic Aortic Aneurysm Disease, and Congenital Deafness

Using a new computational approach they developed to analyze large genetic datasets from rare disease cohorts, researchers at the Icahn School of Medicine at Mount Sinai and colleagues have discovered previously unknown genetic causes of three rare conditions: primary lymphedema (characterized by tissue swelling), thoracic aortic aneurysm disease, and congenital deafness. The work was done in collaboration with colleagues at the University of Bristol, UK; KU Leuven, Belgium; the University of Tokyo; the University of Maryland; Imperial College London, and others from around the world.

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Study Offers Potential Strategy to Improve T Cell Therapy in Solid Tumors; Simultaneous Knockout of Two Inflammatory Regulators Boosts T Cell Expansion in Models

A new approach that delivers a “one-two punch” to help T cells attack solid tumors is the focus of a preclinical study by researchers from the Perelman School of Medicine at the University of Pennsylvania. The findings, published on March 15, 2023 in PNAS, showed that targeting two regulators that control gene functions related to inflammation led to at least 10 times greater T cell expansion in models, resulting in increased antitumor immune activity and durability. The open-access article is titled “Combined Disruption of T Cell Inflammatory Regulators Regnase-1 and Roquin-1 Enhances Antitumor Activity of Engineered Human T Cells.”

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Immobilizing Mosquito Sperm by Inactivating Key Protein

Adult female Culex mosquito taking a blood meal. (Credit CDC).

New UC Riverside (UCR) research makes it likely that proteins responsible for activating mosquito sperm can be shut down, preventing them from swimming to or fertilizing eggs. The study could help control populations of Culex, the common house mosquito that transmits brain-swelling encephalitis and West Nile Virus. “During mating, mosquitoes couple tail to tail, and the males transfer sperm into the female reproductive tract. It can be stored there awhile, but it still has to get from point A to point B to complete fertilization,” said Cathy Thaler, PhD, UCR cell biologist and the study’s first author. Key to completing that journey are the specialized proteins secreted during ejaculation that activate the sperm flagella, or ‘tails,’ that power their movement. 

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