Researchers Show How the COVID-19 Virus Triggers Immune Signaling ‘Storm’ (Medicine)

Researchers have discovered new ways in which the coronavirus disease (COVID-19) virus causes human immune cells to overreact, a deadly part of the disease.

Led by researchers from NYU Grossman School of Medicine and Perlmutter Cancer Center at NYU Langone, the new study found that SARS-CoV-2, the pandemic virus, interacts with specific proteins on immune cells, causing these cells to release abnormally high levels of immune signaling proteins called cytokines (a “cytokine storm”). These cytokines, in turn, cause fluid buildup in the lungs and make it hard to breathe.

Before the current study, SARS-CoV-2 was thought to interact mostly with a protein called angiotensin converting enzyme 2 (ACE2), which is present on the outer surfaces of lung cells. The virus evolved to have a protein spike that snags ACE2 as the first step in invading human lung cells, where the virus multiplies. Accordingly, all approved COVID-19 antiviral drugs and vaccines work by interfering with, or protecting against, this viral spike/ACE2 interaction.

Mounting evidence, however, suggests that the virus also interacts directly with human immune cells, which have little ACE2 on their surfaces. Published online May 9 in the journal Immunity, the new study identified six surface proteins on immune cells that attach to the viral spike protein, but in different places than ACE2.

The virus does not appear to replicate in immune cells, as it does when it binds with ACE2 on lung cells, but instead, the newfound interactions cause damaging immune responses, say the study authors. Based on their new understanding, the team generated nanobodies, a type of protein-based therapeutic, to block viral attachment to both ACE2 and the newfound immune cell surface proteins (receptors).

“Our results suggest that we can simultaneously keep SARS-CoV-2 from invading lung cells while also blocking the dangerous hyperactivation that the viral spike protein causes in immune cells,” says corresponding study author Jun Wang, PhD, assistant professor in the Department of Pathology at NYU Langone. “Such dual action, if confirmed in human studies, could more fully address a disease that has taken more than 3.3 million lives globally.”

In the study, the authors used a technique called single-cell RNA-sequencing to examine which genes were expressed, and consequently, which proteins were built, in cells present in lung fluid taken from patients with COVID-19, including cells lining the lungs (epithelial cells) and immune cells.

Their high-speed receptor screening approach identified and described the six human immune cell membrane proteins that bound to SARS-CoV-2 spike protein. Five were C-type lectins, carbohydrate-binding protein units with many biological functions, including in immune defenses. The authors also found that SARS-CoV-2 spike attaches to Tweety family member 2, a protein that controls the entry of charged particles (chloride) into cells, and possibly a switch that activates immune cells. Importantly, the team found the virus spike interacts with these activating surface proteins mostly on myeloid cells, a group of vital immune cells that arise in bone marrow and circulate in the blood.

In addition, the study authors generated nanobodies that blocked SARS-CoV-2 spike/ACE2 and myeloid cell interactions. Nanobodies are smaller derivatives of antibodies, immune proteins that form a surveillance system by recognizing invading microbes. Industry designs synthetic antibodies that specifically glom onto targets of their choice, which can change the action of disease-causing proteins. More recently, researchers began fine-tuning just pieces of antibodies, called nanobodies, which are easier to make.

“Our study will change how the field thinks about mechanisms behind COVID-19, demonstrating that viruses can directly reprogram immune cells with potentially deadly consequences,” says co-first study author Qiao Lu, PhD, a postdoctoral scholar in Dr. Wang’s lab.

As a next step, he says, the research team plans to explore their nanobody’s potential in preclinical and clinical studies in patients with severe cases of COVID-19, as well as in those with emerging virus mutants that cause more severe symptoms.

Along with Dr. Wang, co-corresponding authors for the study were Siyuan Ding in the Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, and Qi Xie of the Institute of Basics Medical Sciences, Westlake Institute for Advanced Study in Hangzhou, China. Along with Dr. Lu, co-first authors were Jia Liu of the Department of Pathology at NYU Langone; and Shuai Zhao of Westlake University. Study authors from the Department of Pathology at NYU Langone were Triantafyllia Karakousi, Ze Zhang, Xufeng Chen, Marianna Teplova, Tenny Mudianto, Jasper Du, Alberto Herrera, Sergei Koralov, Iannis Aifantis; and Leopoldo Segal in the Department of Medicine; as well as Payal Damani-Yokota, Maria Kaczmarek, Stephen Yeung, Kamal Khanna, and Kenneth Stapleford in the Department of Microbiology.

Additional study authors were Xiaojuan Ran, Hongzhen Tang, Haijing Deng, Zhilin Long, Shumin Jin, Peng Lin, and Ming Zhou of the Institute of Basics Medical Sciences, Westlake Institute for Advanced Study; Maria Florencia, Gomez Castro, Juhee Son, Ruochen Zang, Broc McCune, Rita Chen, and Michael Diamond of the Washington University School of Medicine, St. Louis; Maudry Laurent-Rolle, Jack Hsu, Tina Tianjiao Su, and Peter Cresswell of the Department of Immunobiology at Yale University School of Medicine; Jianbo Dong, Betty Huang, and Yue Liu of Ab Studio Inc.; Fei Tang, Xianwen Ren, and Zemin Zhang of the Beijing Advanced Innovation Center for Genomics at Peking University; Renhong Yan and Qiang Zhou of the Joint Research Center of Hangzhou First Hospital Group and Westlake University; Jia Cui of Kactus Biosystems in Shanghai; James Zhu and Tao Wang of the Quantitative Biomedical Research Center at University of Texas Southwestern Medical Center; and Jianzhu Ma of the Department of Computer Science at Purdue University.

This work is supported by internal funds provided by the Office of Science and Research at NYU Langone, Westlake Education Foundation, Tencent Foundation grant XHTX202001008, Hangzhou Science and Technology Development Foundation grant 20202013A05, a Cancer Research Institute Irvington Postdoctoral Fellowship, and National Institutes of Health grants P30 DK052574, R00 AI135031, R01 AI150796, R01 AI157155, R01 AI143861, AI143861S1, and R01-AI059167. Dr. Wang, Dr. Lu, and Dr. Liu from NYU Langone; and Dr. Huang, Dr. Dong, and Dr. Yue Liu from Ab Studio Inc., are named as inventors on patent applications that describe the anti-SARS-CoV-2 blocking nanobodies. Dr. Wang is also a paid consultant for Lilly Asia Ventures and Rootpath Genomics (work not related to the current study).

Featured image: GETTY/FOTOGRAZIA

Reference: Qiao Lu, Jia Liu, Shuai Zhao et al., “SARS-CoV-2 exacerbates proinflammatory responses in myeloid cells through C-type lectin receptors and Tweety family member 2”, Immunity, 2021. DOI:

Provided by NYU Langone

Weighted “Lottery” Provides Greater Access To Scarce COVID-19 Medications (Medicine)

A weighted “lottery” designed to increase access to the antiviral drug remdesivir during the May-July 2020 COVID-19 surge for those most affected by the coronavirus, including members of the Black, Latinx and indigenous communities, led to more equitable distribution of the badly needed medication, according to research presented at the ATS 2021 International Conference.

At a time when supplies of COVID-19 medications were scarce, Douglas B. White, MD, MAS, vice chair and professor of critical care medicine, UPMC endowed chair for ethics in critical care medicine and director of the Program on Ethics and Decision Making in Critical Illness, University of Pittsburgh School of Medicine, and colleagues, convened a multi-institution consortium of experts to develop a weighted lottery, in which some patients would be given higher priority for receiving remdesivir while others would be given lower priority.

Consortium members had expertise in bioethics, economics, health disparities, medicine, pharmacy and health law. They assigned more weight to patients from disadvantaged communities and essential workers, and less weight to patients expected to die within a year from a terminal condition and those with severe respiratory failure.

The lottery was implemented at 23 hospitals across the UPMC health system during periods of drug shortage. The team identified eligible patients using an electronic health record- and telephone-based screening system. They calculated the number of potentially eligible patients each week, based on the number of patients who were eligible the previous week. Using the weighting system previously described, a drug allocation team met each day to determine each eligible patient’s chance of receiving the drug, and then used a random number generator to run the lottery.

Overall, 61 percent of the available remdesivir was allocated to patients who were from disadvantaged neighborhoods and/or were essential workers. These individuals made up 56 percent of the COVID-19 patient population.

“We showed that in the maelstrom of a pandemic it is possible to deploy an organized allocation strategy that promotes both equity and clinical benefit,” said Dr. White.

“This is a major improvement over the first-come, first-served approach that many hospitals have used; that approach is likely to worsen disparities for those with access-to-care barriers. Among those most affected would be persons with disabilities that limit their mobility and those without health insurance, who may delay seeking care due to financial concerns.”

He noted that the weighted lottery also allows planners to give priority to certain groups, such as those who are most likely to benefit and those who have been disproportionately affected by the pandemic, such as individuals from hard-hit communities.

“It was our goal from the outset to develop a framework and process that any hospital can use,” stated Dr. White. The team also developed a detailed protocol that describes the steps to carry out the lottery, which can be found here.

The researchers concluded that it is best to implement the lottery on a centralized, regional level, rather than hospital-by-hospital. “It is far more efficient to conduct one lottery for many hospitals than have each hospital conduct its own lottery. This approach can simultaneously accomplish fair allocation and rapid learning, because the lottery creates a natural experiment in which some patients receive the scarce drug while others do not. Researchers can use the lottery’s registry to assess the effectiveness of the drug.” This is described in detail in this article.

Reference: D. B. White, E. McCreary, P. Pathak, T. Sonmez et al., “Developing and Implementing a Weighted Lottery to Equitably Allocate Scarce COVID-19 Medications”, ATS Conference, 2021.

Provided by American Thoracic Laboratory

Zapping Nerves With Ultrasound Lowers Drug-resistant Blood Pressure (Medicine)

Brief pulses of ultrasound delivered to nerves near the kidney produced a clinically meaningful drop in blood pressure in people whose hypertension did not respond to a triple cocktail of medications, reports a new study led by researchers at Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian.

In a clinical trial of the procedure, called renal denervation, daytime blood pressure after two months had dropped 8 points compared to a 3-point drop in patients who were treated with a sham procedure. Nighttime blood pressure decreased by an average of 8.3 points in the treatment group versus 1.8 points in the sham group.

“For patients with drug-resistant hypertension, a drop in blood pressure of 8 points–if maintained over longer-term follow-up–is almost certainly going to help reduce the risk of heart attack, stroke, and other adverse cardiac events,” says Ajay Kirtane, MD, professor of medicine at Columbia University Vagelos College of Physicians and Surgeons, an interventional cardiologist at NewYork-Presbyterian/Columbia University Irving Medical Center, and co-principal investigator of the trial.

“These results suggest that renal denervation has potential to become an important add-on to medication therapy–including for those who have difficulty managing several medications to control their hypertension.”

Data from the trial, called RADIANCE-HTN TRIO, were presented May 16 at the American College of Cardiology conference and simultaneously published in The Lancet.

The treatment is still experimental, has not been approved for use by the FDA, and is only available through clinical trials. The trial will follow patients for five years to determine if the drop in blood pressure is maintained over time.

Need for Additional Blood Pressure-Lowering Therapies

About two-thirds of people who take medications to lower blood pressure are able to control their condition. But in others, the drugs do not work or people do not take them as directed.

“There are a variety of effective medications for lowering blood pressure, but many people need to take several drugs to control their hypertension, which can have side effects. In addition, many people simply don’t want to take additional medications and are poorly adherent to them,” says Kirtane. “It’s clear that we need additional therapeutic approaches to help patients get their blood pressure under control.”

Why Renal Denervation?

The kidney plays a role in blood pressure by controlling how much water is in the bloodstream (more water = more pressure) and acting as a central signaling center for other systems that regulate blood pressure. Renal denervation, a minimally invasive procedure, uses ultrasound energy to disrupt signals from overactive nerves in the renal arteries. The therapy is delivered via a catheter that is threaded through an artery in the leg.

Targeting these nerves is not a new idea in hypertension treatment; several existing medications reduce renal nerve activity to reduce blood pressure.

“But unlike medications, which are only effective when you take them, renal denervation is a therapy that’s always ‘on,'” Kirtane says.

Initial studies of renal denervation had several flaws–including the lack of an adequate control group, variable measurement of participants’ blood pressure, and frequent changes in background medications–that made the results challenging to interpret.

How the Study Worked

In this study, the researchers tested the effectiveness and safety of a device that delivers two to three short blasts of ultrasound to nerve fibers that travel close to the renal artery.

The study included adults with moderate to severe hypertension despite taking three or more antihypertensive drugs. All of the patients were switched to the same medication regimen for their hypertension. (To help with patient adherence, participants took a single pill that combined three commonly used antihypertensive drugs.)

“In our study, 80% of patients continued to take their medication as directed, and while that’s a good adherence rate, it still means that one in five patients weren’t adherent to the medication regimen,” Kirtane adds.

Of 136 patients whose blood pressure remained high after four weeks on the new regimen, 69 were treated with renal denervation and 67 had the sham procedure.

Previous studies in patients with less severe hypertension who were not taking any antihypertensive medications showed that renal denervation was more effective than a sham procedure in lowering blood pressure.

“Additional studies will be needed to determine if this therapy may be effective for other groups, including older patients with hypertension and those with chronic kidney disease,” says Kirtane.

More Information

The study, titled “Ultrasound renal denervation for hypertension resistant to triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial,” was published online in The Lancet on May 16, 2021.

Michel Azizi (Université de Paris, France) and Ajay J. Kirtane (Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian), co-corresponding authors, contributed equally to the manuscript. Additional authors are listed in the article.

The study was funded by ReCor Medical, Inc., the manufacturer of the Paradise Renal Denervation System.

Provided by Columbia University Irving Medical Center

Squirrels Help Scientists Understand How We Sense Heat (Biology)

The first complete high-res image of a heat-sensing molecule in ground squirrels is helping researchers understand how we sense temperature and could lead to the development of new pain relievers.

Ground squirrels, like other mammals, sense environmental temperatures with molecules called TRPV1 receptors that dot the surface of sensory nerves.

Cryo-EM map of the TRPV1 receptor. From Nadezhdin et al. (2021)

But unlike most mammals, ground squirrels love the heat. Ground squirrels—which look like a cross between a prairie dog and a chipmunk—thrive in hot climates, partly because their TRPV1 receptors are not activated by extreme heat. Even at temperatures of 115 F (46 C) degrees, ground squirrels are content, and their TRPV1 receptors remain unmoved.

“Understanding how the ground squirrel TRPV1 senses heat could also provide clues to how human TRPV1s sense heat, which is also not understood,” says Alexander Sobolevsky, PhD(link is external and opens in a new window), associate professor of biochemistry & molecular biophysics at Columbia University Vagelos College of Physicians and Surgeons, who led the imaging study.

To obtain images, the researchers first synthesized ground squirrel TRPV1 molecules in the lab and then put them under an electron microscope, using cryo-EM techniques pioneered by Columbia Nobel laureate Joachim Frank, PhD, professor of biochemistry & molecular biophysics.

The new images are the first of a full-size TRPV1 and they reveal that the receptor’s cap—which previous studies had failed to capture—plays an essential role in temperature detection. 

TRPV1 not only senses physical heat, it also detects the spicy heat of chili peppers but by a different mechanism. The researchers captured images of capsaicin, the molecule behind the heat, bound to TRPV1, which show that the molecule displaces an essential lipid in the cellular membrane that is also thought to be involved in sensing high temperatures. More research will be needed to fully understand how TRPV1 is activated by heat, capsaicin, and other molecules.

New images of the TRPV1 receptor are starting to reveal how the molecule senses both hot temperatures and the heat of chili peppers (via the pepper’s capsaicin). The cap plays an important role in temperature sensing, but capsaicin activates the receptor through a different mechanism. Image from Alexander Sobolevsky. 

TRPV1 receptors are also involved in pain, and additional images should also help in the design of new pain relievers that target TRPV1. TRPV1 receptors also have been found outside the sensory system and are being investigated as treatments for inflammatory bowel disease, cancer, and other conditions. 

“The new details we’re getting from the complete image of TRPV1 are telling us how the molecule works,” says Kirill Nadezhdin, a postdoctoral fellow in Sobolevsky’s lab and first author of the paper, “which is information that can help in the design of new treatments.”

More information

The study, titled “Extracellular cap domain is an essential component of the TRPV1 gating mechanism(link is external and opens in a new window),” was published April 12, 2021, in Nature Communications.

The authors: Kirill D. Nadezhdin (Columbia University), Arthur Neuberger (Columbia University), Yury A. Nikolaev (Yale University), Lyle A. Murphy (Yale University), Elena O. Gracheva (Yale University), Sviatoslav N. Bagriantsev (Yale University), and Alexander I. Sobolevsky (Columbia University).

The research was supported by the U.S. National Institutes of Health (grants 1R01NS091300, 1R01NS097547, R01CA206573, R01NS083660, and R01NS107253), and the U.S. National Science Foundation (grants 1754286, 1923127, and 1818086). 

The work was performed at the Columbia University Cryo-Electron Microscopy Center, the National Center for CryoEM Access and Training (NCCAT), and the Simons Electron Microscopy Center located at the New York Structural Biology Center, supported by the NIH Common Fund Transformative High-Resolution Cryo-Electron Microscopy program (U24 GM129539), and by grants from the Simons Foundation (SF349247) and the New York State Assembly.

Provided by Columbia University Irving Medical Center

Why Does It Take So Long To Make Decisions? (Neuroscience)

Thinking is a surprisingly slow process because our brain cannot make multiple decisions about the same object at once, Columbia neuroscientists have found. New experiments probe how we make decisions

Every thought involves multiple decisions. How does the brain juggle those decisions while accumulating evidence about the world?

For the past decade, Professor Michael Shadlen, MD, PhD, has been exploring this question. Described in the video below, new experiments that showed volunteers colorful dots moving on a screen have yielded some answers—and revealed a bottleneck in the decision-making process.

The work was carried out by Yul Kang, now a research associate at the University of Cambridge; Postdoctoral Fellow Anne Löffler, PhD, in the laboratory of Daniel Wolpert, PhD; Postdoctoral Researcher Danique Jeurissen, PhD, in the Shadlen lab; and Assistant Professor Ariel Zylberberg, PhD, at the University of Rochester. It appears in the journal eLife.

Featured image: Michael N. Shadlen, MD, PhD © Zuckerman Institute

Provided by Zuckerman Institute Columbia

Multimodal Therapy May Hold Key To Treating Aggressive Childhood Cancer (Medicine)

Research led by scientists at Children’s Cancer Institute and published this week in the international journal, Clinical Cancer Research, has found a combination of therapies that appears to be highly effective against high-risk neuroblastoma and other forms of aggressive childhood cancer.

Up to half of all cases of neuroblastoma newly diagnosed in children are ‘high-risk’, meaning the cancer grows aggressively and is difficult to treat. Despite receiving intensive treatment, most children with high-risk disease die within five years of diagnosis, while those who survive are often left with serious long-term health effects.

Professor Michelle Haber AM, a senior author on the paper and co-head of the Molecular Targets and Cancer Therapeutics theme at Children’s Cancer Institute, said children diagnosed with high-risk neuroblastoma have less than a 50-50 chance of survival. “That is a devastating prognosis. We are absolutely determined to find better ways to treat this disease and improve that survival rate.”

The research focuses on two different types of therapies, both of which have been found to be effective against high-risk neuroblastoma in the laboratory. The first, CBL0137, is a compound called a curaxin, structurally similar to antimalarial drugs. The second is panobinostat, a new type of compound known as a histone deacetylase inhibitor. In the new research, the scientists tested whether the two therapies could work synergistically when used together, each enhancing the anticancer effect of the other.

The researchers found that the two compounds did indeed work well together, effectively inhibiting the growth of cancer cells in culture, as well as in mice bred to develop human high-risk neuroblastoma. As an added bonus, the therapies also jointly acted to heighten the body’s immune response to cancer, which is important since immunotherapy in neuroblastoma is currently challenging.

“In our experiments, we found that the combination of CBL0137 and panobinostat resulted in remarkable growth suppression and an immune response that was tumour-specific,” said Professor Haber. “This is very encouraging, because ideally you want a cancer treatment to specifically target cancer cells and leave healthy cells unharmed, reducing the problem of side effects.”

Dr Lin Xiao, joint first author and Research Officer in the Experimental Therapeutics Group at the Institute added, “When we used these two compounds together in mice with high-risk neuroblastoma, we saw complete and lasting tumour regression, with minimal ill-effects on the mice. Our results suggest that this combination could work well as a type of immunotherapeutic approach to treating high-risk neuroblastoma.”

Further research at Children’s Cancer Institute has shown that this type of multimodal therapy is also effective against other high-risk childhood cancers, including some forms of brain cancer. Together, it is hoped these results will lead to a new therapy for aggressive childhood cancer.

This work was supported by funding from Cancer Institute NSW, Neuroblastoma Australia, the Kids Cancer Alliance (KCA), Tenix Foundation, Anthony Rothe Memorial Trust, the National Health and Medical Research Council (NHMRC), the Goodridge Foundation, Stanford Brown, Inc (Sydney, Australia), Cancer Council NSW and Tour de Cure.

This science news is confirmed by us from Children’s Cancer Institute

Provided by Children’s Cancer Institute

About Children’s Cancer Institute

Originally founded by two fathers of children with cancer in 1976, Children’s Cancer Institute is the only independent medical research institute in Australia wholly dedicated to research into the causes, prevention and cure of childhood cancer. Forty years on, our vision is to save the lives of all children with cancer and improve their long-term health, through research. The Institute has grown to now employ over 300 researchers, operational staff and students, and has established a national and international reputation for scientific excellence. Our focus is on translational research, and we have an integrated team of laboratory researchers and clinician scientists who work together in partnership to discover new treatments which can be progressed from the lab bench to the beds of children on wards in our hospitals as quickly as possible. These new treatments are specifically targeting childhood cancers, so we can develop safer and more effective drugs and drug combinations that will minimise side-effects and ultimately give children with cancer the best chance of a cure with the highest possible quality of life. More at

Novel Monoclonal Antibody Can Substantially Lower Triglycerides in Patients With Acute Pancreatitis (Medicine)

The investigational drug evinacumab reduced triglycerides in patients with severe hypertriglyceridemia (sHTG) and a history of hospitalizations for acute pancreatitis in a phase 2 global study led by Mount Sinai. The fully human monoclonal antibody produced sustained reductions in triglyceride levels of up to 82 percent, depending on the patient’s genotype, while also lowering the risk of recurrent acute pancreatitis. The results of the study will be presented as a late-breaking clinical trial at the American College of Cardiology (ACC) Annual Scientific Session, on May 16.

“Evinacumab has the potential to not only lower triglycerides, but the risk of acute pancreatitis, quality of life, and the risk of cardiovascular events in a highly vulnerable patient population,” says Robert S. Rosenson, MD, Professor of Medicine at the Icahn School of Medicine at Mount Sinai, and lead investigator of the study. “The unmet clinical need couldn’t be greater. Even after the current therapeutic options of dietary counseling, fibrates, and omega-3 fatty acid products, many individuals with severe hypertriglyceridemia have elevated triglyceride levels above 500 mg/dL, and some in the thousands.”

Severe hypertriglyceridemia, defined as triglycerides greater than 500 mg/dL, is believed responsible for around 10 percent of all cases of acute pancreatitis which affects more than 200-thousand patients a year in the United States. It is an inflammatory condition of the pancreas that causes abdominal pain and fever and, in some individuals, can be life-threatening. Recurrent acute pancreatitis typically requires frequent hospitalizations and the most common causes are gallstones and alcoholism.

In their study of 52 patients with severe hypertriglyceridemia, researchers found that clinical improvements depended on genetic variants. The greatest triglyceride reductions, up to 82 percent, occurred in a cohort of patients without two mutations in the lipoprotein lipase (LPL) pathway. LPL is an enzyme responsible for metabolizing, or breaking down, triglycerides. In a second cohort of patients with a genetic disorder known as multifactorial chylomicronemia syndrome (MCS)–which can be exacerbated by comorbidities, medications, and even lifestyles–triglycerides were reduced by around 65 percent. And in a third cohort–of those with loss of function mutations in two genes encoding lipoprotein lipase, a condition known as familial chylomicronemia syndrome (FCS)–there was no reduction in triglyceride levels.

“Our research underscored the importance of genetic testing of the LPL pathway to determine which patients are most likely to respond well to evinacumab therapy,” says Dr. Rosenson, who is Director of Metabolism and Lipids for the Mount Sinai Health System. “Even in patients with two LPL mutations who experienced no reduction in triglycerides, there were reductions in non-HDL cholesterol and in the cholesterol content of triglyceride-rich lipoproteins, demonstrating that evinacumab was impacting the triglyceride pathway.”

Evinacumab works by binding to and blocking the function of angiopoietin-like protein 3 (ANGPTL3), a protein thought to play a role in cholesterol metabolism. People who are missing or have very low ANGPTL3 due to genetic causes are known to have significantly reduced lipid levels, suggesting to scientists that it could also be a therapeutic target for lowering triglycerides.

Evinacumab, from Regeneron Pharmaceuticals, was approved by the U.S. Food and Drug Administration in February 2021 (under the name Evkeeza™) for homozygous familial hypercholesterolemia, an inherited disorder that makes it difficult for the body to eliminate LDL cholesterol (so-called “bad cholesterol”) from the blood.

The next clinical trial for evinacumab in patients with severe hypertriglyceridemia is designed to evaluate the reduction in the risk of acute pancreatitis and is expected to begin shortly, with Mount Sinai again playing a pivotal global role. “Based on the results we’ve seen to date, we believe evinacumab can significantly decrease the risk of recurrent acute pancreatitis in people with severely elevated triglycerides,” says Dr. Rosenson. “At the same time, this novel drug could help to ease the financial burden on a health system which provides ongoing care for these high-risk patients who are frequently hospitalized for recurrent episodes of acute pancreatitis.”

This science news is confirmed by us from mount sinai health system

Provided by Mount Sinai Health System

About the Mount Sinai Health System

The Mount Sinai Health System is New York City’s largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai is a national and international source of unrivaled education, translational research and discovery, and collaborative clinical leadership ensuring that we deliver the highest quality care–from prevention to treatment of the most serious and complex human diseases. The Health System includes more than 7,200 physicians and features a robust and continually expanding network of multispecialty services, including more than 400 ambulatory practice locations throughout the five boroughs of New York City, Westchester, and Long Island. Mount Sinai Heart at The Mount Sinai Hospital is within the nation’s No. 6-ranked heart center, and The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report’s “Honor Roll” of the Top 20 Best Hospitals in the country and the Icahn School of Medicine as one of the Top 20 Best Medical Schools in country. Mount Sinai Health System hospitals are consistently ranked regionally by specialty and our physicians in the top 1% of all physicians nationally by U.S. News & World Report.

For more information, visit or find Mount Sinai on Facebook, Twitter and YouTube.

How A Compact Object Of 2.6 Solar Mass In GW 190814, Could Be A Neutron Star? (Cosmology)

Berryman and Gardner consider the possibility of a new force between quarks, which modifies the neutron star equation of state, particularly at supranuclear densities. Thereby making them heavy.

On 23 June 2020, the LIGO Scientific Collaboration and the Virgo Collaboration announced the discovery of a gravitational wave binary, GW190814. While one component of this binary is a 23 solar-mass black hole, the other component is a compact object of 2.6 solar mass, which may be too massive to be a neutron star, given our current knowledge of the nuclear matter equation of state. Now, J. Berryman and S. Gardner with the help of a new physics model (within a non-relativistic many body framework) proposed that, it is possible that a neutron star can be so heavy, if a new force exists between quarks and it modifies the neutron star equation of state, particularly at supranuclear densities. Their study recently appeared in Arxiv.

“This new force between quarks can make neutron stars for a fixed equation of state and many-body method both heavier and puffier.”

— told Susan Gardner, professor at University of Kentucky and one of the author of the study

They considered minimal extensions of the Standard Model (SM) that give rise to new, short-range interactions between quarks. In particular, they considered U(1)X gauge symmetry extensions that couple to baryon number. If this symmetry is spontaneously broken it would give a gauge boson X. If this boson is heavier than the pion and not too strongly coupled, then its effects on nuclear matter (or on nucleon-nucleon force) are expected to be subdominant to those of the strong interactions, comprising at most some part of the empirical low energy constants (LECs). These effects can modify the neutron matter equation of state at supranuclear densities.

“This new interaction is largely shielded from constraints from low-energy experiments. In particular, its contribution to the nucleon-nucleon (NN) force can be hidden within the short-distance repulsion of the phenomenological NN force in the SM, yet it can modify the neutron matter equation of state (EoS) at supranuclear densities”

— told S. Gardner

They also evaluated how this modification can impact a neutron star’s mass and radius to make the observed heavy compact object more probably a neutron star, rather than a black hole. By combining spin effects with new physics, it has been found that it could yield heavy neutron stars (NSs); thus more compact objects in excess of 2M may eventually be identified, promoting the possibility of new baryonic interactions.

“Although we have not resolved the nature of the ~ 2.6 M compact object in GW190814, this mechanism allows it to more naturally be a neutron star.”

— told S. Gardner.

Finally, they concluded that their new physics scenario can be tested through studies of rare η and η’ decays and of X photoproduction at low-energy accelerators.

Reference: Jeffrey M. Berryman, Susan Gardner, “Neutron stars and the secret lives of quarks”, Arxiv, pp. 1-7, 2021.

Note for editors of other websites: To reuse this article fully or partially kindly give credit either to our author S. Aman or provide a link of our article

Alien Radioactive Element Prompts Creation Rethink (Planetary Science)

The first-ever discovery of an extraterrestrial radioactive isotope on Earth has scientists rethinking the origins of the elements on our planet.

The tiny traces of plutonium-244 were found in ocean crust alongside radioactive iron-60. The two isotopes are evidence of violent cosmic events in the vicinity of Earth millions of years ago.

Star explosions, or supernovae create many of the heavy elements in the periodic table, including those vital for human life, such as iron, potassium and iodine.

To form even heavier elements, such as gold, uranium and plutonium it was thought that a more violent event may be needed, such as two neutron stars merging.

However, a study led by Professor Anton Wallner from The Australian National University (ANU) suggests a more complex picture.

“The story is complicated – possibly this plutonium-244 was produced in supernova explosions or it could be left over from a much older, but even more spectacular event such as a neutron star detonation,” lead author of the study, Professor Wallner said.

Any plutonium-244 and iron-60 that existed when the Earth formed from interstellar gas and dust over four billion years ago has long since decayed, so current traces of them must have originated from recent cosmic events in space.

The dating of the sample confirms two or more supernova explosions occurred near Earth.

“Our data could be the first evidence that supernovae do indeed produce plutonium-244,” Professor Wallner said

“Or perhaps it was already in the interstellar medium before the supernova went off, and it was pushed across the solar system together with the supernova ejecta.”

Professor Wallner also holds joint positions at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and Technical University Dresden in Germany, and conducted this work with researchers from Australia, Israel, Japan, Switzerland and Germany.

The VEGA accelerator at Australian Nuclear Science and Technology Organisation, (ANSTO) in Sydney was used to identify the tiny traces of the plutonium-244.

The study has been published in Science.

Featured image: This false-color composite from NASA Spitzer Space Telescope and NASA Chandra X-ray Observatory shows the remnant of N132D. Credit: NASA/JPL-Caltech/Harvard-Smithsonian CfA

References: (1) A. Wallner et al. 60Fe and 244Pu deposited on Earth constrain the r-process yields of recent nearby supernovae, Science (2021). DOI: 10.1126/science.aax3972 (2) Daniel Clery. Trace seabed plutonium points to stellar forges of heavy elements, Science (2021). DOI: 10.1126/science.abj4596

Provided by Australian National University