Publisher Health

An experimental, lab-made antibody can completely prevent nonhuman primates from being infected with the monkey form of HIV, new research published in Nature Communications shows.
The results will inform a future human clinical trial evaluating leronlimab as a potential pre-exposure prophylaxis, or PrEP, therapy to prevent human infection from the virus that causes AIDS.
“Our study findings indicate leronlimab could be a new weapon against the HIV epidemic,” said the study’s lead researcher and co-corresponding author of this paper, Jonah Sacha, Ph.D., an Oregon Health & Science University professor at OHSU’s Oregon National Primate Center and Vaccine & Gene Therapy Institute.
“The results of this pre-clinical study, targeting the HIV co-receptor CCR5, have the potential to be groundbreaking as we essentially have a tool that can mimic the genetic mutations of CCR5 that render some individuals immune to infection and have led in part to two cases of a cure of HIV,” said the other co-corresponding author, Lishomwa Ndhlovu, M.D., Ph.D., a professor of immunology in medicine at Weill Cornell Medicine in New York.
Made by Vancouver, Washington-based CytoDyn, the monoclonal antibody blocks HIV from entering immune cells through a surface protein called CCR5. The injectable drug has already been studied in a Phase 3 trial as a potential treatment for people living with HIV when used in combination with standard antiretroviral medications. CytoDyn is in the process of submitting information to the FDA to request its approval for that use. This study, however, specifically examined preventing HIV infection to begin with.
Some PrEP drugs are already available, but they can lead to adverse side effects such as liver, heart and bone problems, and some people are resistant to them due to genetic mutations in HIV. Existing PrEP options typically require frequent use, such as a pill daily, or are infusions that must be given in a clinic. Leronlimab is designed to be a self-administered injection.
To study leronlimab’s effectiveness as a potential PrEP drug, the research team created three groups of six rhesus macaques at OHSU’s Oregon National Primate Research Center. Two groups received different doses of leronlimab, while the third served as a control that didn’t receive the experimental drug.
Macaques that received the higher dose of 50 milligrams per kilogram of the animal’s weight every other week were completely protected from the monkey form of HIV. In contrast, two of the animals that received the lower dose of 10 milligrams per kilogram per week became infected, and every animal in the control group became infected. Researchers concluded the low-dose group’s partial protection was likely due to monkey immune responses against the human antibody.
Following this study’s results, CytoDyn is planning to conduct an early clinical trial investigating leronlimab as a potential PrEP drug in people within the next year. Human doses would likely be lower than those given in this study, as rhesus macaque cells have more surface CCR5 protein than humans.
In the meanwhile, Sacha is already trying to make leronlimab easier to use. He received a five-year, $3-million NIH grant in August 2020 to develop a concentrated, longer-lasting formulation of leronlimab that could allow it to be injected every three months. Less-frequent injections can increase drug regimen adherence, and therefore improve drug effectiveness.
The research team dedicated this study to Timothy Ray Brown, who died Sept. 29, 2020, and was known as the Berlin patient for being the first person to be cured of HIV. While living in Berlin in 2007, Brown underwent a bone morrow transplant to treat his blood cancer. The procedure eliminated HIV in Brown because the transplanted bone marrow came from a donor who had a rare mutation that eliminated the CCR5 gene, which makes the surface protein through which HIV enters cells. Sacha became friends with Brown after meeting him at an AIDS conference in 2015. Brown is also a co-author on the paper, and inspired scientists working on this research.

Heart attacks and strokes — the leading causes of death in human beings — are fundamentally blood clots of the heart and brain. Better understanding how the blood-clotting process works and how to accelerate or slow down clotting, depending on the medical need, could save lives.
New research by the Georgia Institute of Technology and Emory University published in the journal Biomaterials sheds new light on the mechanics and physics of blood clotting through modeling the dynamics at play during a still poorly understood phase of blood clotting called clot contraction.
“Blood clotting is actually a physics-based phenomenon that must occur to stem bleeding after an injury,” said Wilbur A. Lam, W. Paul Bowers Research Chair in the Department of Pediatrics and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. “The biology is known. The biochemistry is known. But how this ultimately translates into physics is an untapped area.”
And that’s a problem, argues Lam and his research colleagues, since blood clotting is ultimately about “how good of a seal can the body make on this damaged blood vessel to stop bleeding, or when this goes wrong, how does the body accidentally make clots in our heart vessels or in our brain?”
How Blood Clotting Works
The workhorses to stem bleeding are platelets — tiny 2-micrometer cells in the blood in charge of making the initial plug. The clot that forms is called fibrin, which acts as a glue scaffold that the platelets attach to and pull against. Blood clot contraction arises when these platelets interact with the fibrin scaffold. To demonstrate the contraction, researchers embedded a 3-millimeter mold with millions of platelets and fibrin to recreate a simplified version of a blood clot.

A new study from researchers at Johns Hopkins Bloomberg School of Public Health and colleagues suggests a slowdown in the use of convalescent plasma to treat hospitalized COVID-19 patients led to a higher COVID-19 mortality during a critical period during this past winter’s surge.
U.S. hospitals began treating COVID-19 patients with convalescent plasma therapy — which uses antibody-rich blood from recovered COVID-19 patients — in the summer of 2020 when doctors were looking to identify treatments for the emerging disease. By the spring of 2021, doctors in the United States had treated over 500,000 COVID-19 patients with convalescent plasma. The use of convalescent plasma started declining late in 2020 after several large clinical trials showed no apparent benefit.
The researchers’ analysis suggests that the decline in convalescent plasma use might have led to more than 29,000 excess COVID-19 deaths from November 2020 to February 2021.
The study was published online June 4 in the journal eLife.
“Clinical trials of convalescent plasma use in COVID-19 have had mixed results, but other studies, including this one, have been consistent with the idea that it does reduce mortality,” says study senior author Arturo Casadevall, MD, PhD, Alfred and Jill Sommer Professor and Chair of the Department of the Molecular Microbiology and Immunology at the Bloomberg School.
The study was done in collaboration with researchers at Michigan State University and the Mayo Clinic. Casadevall and colleagues observed that while plasma use was declining late last year, the reported COVID-19 patient mortality rate was rising. That led them to hypothesize that the two phenomena were related.

Researchers from the Hubrecht Institute in Utrecht (The Netherlands) and the Max Planck Institute for Molecular Biomedicine in Münster (Germany) used computer simulations to reveal in atomic detail how a short piece of DNA opens while it is tightly wrapped around the proteins that package our genome. These simulations provide unprecedented insights into the mechanisms that regulate gene expression. The results were published in PLOS Computational Biology on the 3rd of June, 2021.
Every cell in the body contains two meters of DNA. In order to fit all the DNA in the cell’s small nucleus, the DNA is tightly packed in a structure known as chromatin. Chromatin is an array of identical smaller structures named nucleosomes. In a single nucleosome, DNA is wrapped around 8 proteins called histones. Chromatin is not uniformly compact across the genome. The tightness of the packaging is important in regulating which genes are expressed and therefore which proteins are produced by a cell.
Transitions from tightly to loosely packed DNA — from closed to open chromatin — are essential for cells to convert to another cell type. These cell conversions are hallmarks of development and disease, but are also often used in regenerative therapies. Understanding how such transitions occur may contribute to understanding diseases and optimizing therapeutical cell type conversions.
Computational nanoscope
One step in the opening of chromatin is the motion of DNA while wrapped in nucleosomes. Like all molecular structures in our cells, nucleosomes are dynamic. They move, twist, breathe, unwrap and wrap again. Visualizing these motions using experimental methods is often very challenging. One alternative is to use the so-called “computational nanoscope.”
Researchers use the term computational nanoscope to refer to a set of computer simulation methods. These methods enable them to visualize the movements of molecules over time. Over the past years, the methods have become so accurate that researchers started referring to them as a computational nanoscope; observing the molecules moving on the computer is similar to observing them under a very high resolution nanoscope.

New research identified a novel interaction between the SARS-CoV-2 spike protein and the galectin-3-binding protein (LGALS3BP) which could be a new therapeutic anti-viral target. The research also found the presence of detectable viral RNA in blood in COVID-19 patients is a strong predictor of mortality.
The paper, published today in Nature Communications, was led by a group of researchers from King’s College London, Guy’s and St Thomas’ NHS Foundation Trust and King’s British Heart Foundation Centre. The research was funded by the NIHR Guy’s and St Thomas’ Biomedical Research Centre and supported by grants from BHF.
In the study, authors analysed close to 500 blood samples from patients admitted to Guy’s and St Thomas’ and King’s College Hospitals. The authors compared plasma and serum samples between patients admitted to intensive care units (ICU) with COVID-19 and hospitalised non-ICU COVID-19 patients and non-COVID-19 patients in ICU.
Almost a quarter of COVID-19 ICU patients had detectable RNAemia — severe acute respiratory syndrome coronavirus 2 RNA — within the first six days of admission to ICU. The presence of RNAemia was a strong predictor of 28-day mortality. RNAemia was detectable in 56% of deceased patients but in only 13% of survivors.
Researchers also identified LGALS3BP as a binding protein to the SARS-CoV-2 spike protein
Rising levels of LGALS3BP in the lungs offered protection to cells from the harmful effects of the SARS-CoV-2 spike protein.
The identification of LGALS3BP as a potential antiviral protein is encouraging as the UK government launched an Antivirals Taskforce in April 2021 to find effective treatments that could prevent future waves of infections and limit the effect of new variants.
Professor Manu Shankar Hari, a NIHR Clinician Scientist based at King’s College London and a Consultant in Critical Care Medicine at Guy’s and St Thomas’, said: “We report that presence of detectable viral RNA in plasma or serum of COVID-19 patients is associated with increased risk of severe illness. We also highlight a novel interaction with potential antiviral effect between the SARS-CoV-2 spike protein and a protein called galectin-3-binding protein. Our research findings have two main implications. First, there is an unmet diagnostic technology need for near patient tests to identify presence of viral RNA in blood in COVID-19 patients. Second, our research potentially highlights an antiviral drug target, which is a priority area highlighted within the UK government’s launch of a COVID-19 antivirals Taskforce.”
Professor Manuel Mayr, British Heart Foundation Professor at King’s College London, said: “As British Heart Foundation Professor I am delighted that we could join forces with our clinical colleagues to contribute to a better understanding of COVID-19. This is the first time blood proteins with the ability to bind to the SARS-CoV-2 spike protein have been analysed thanks to the specialised equipment available in King’s British Heart Foundation Centre.”
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Cows can pass on the hypoglycin A toxin through their milk, a study by the Martin Luther University Halle-Wittenberg (MLU) and the Leibniz Institute of Plant Biochemistry (IPB) in Toxins shows. The substance can cause severe symptoms in humans and animals. Small amounts of the toxin were detected in the raw milk of cows that grazed in a pasture exposed to sycamore maple. The team calls for further investigations to realistically assess the potential dangers.
High concentrations of hypoglycin A can be found in unripe akee and lychee fruit and in the seeds and seedlings of various maple trees. These include, for example, the sycamore maple, which is common throughout Europe. The toxin can cause severe illness in humans. In 2017, a team of researchers in India was able to prove that the toxin was responsible for the sudden death of several hundred children in the country who had previously eaten large quantities of lychee. “The substance interferes with the body’s energy metabolism. One typical symptom in humans is very low blood sugar levels,” says Professor Annette Zeyner from the Institute of Agricultural and Nutritional Sciences at MLU. In 2013, hypoglycin A from maple trees was also found to cause atypical myopathy in horses — a puzzling disease that is often fatal for animals kept on a pasture.
Zeyner and her team joined forces with Dr Jörg Ziegler from IPB to discover whether hypoglycin A could also be detected in the raw milk of cows. “Maple trees are widespread and grazing cows is a common practice. Thus, it seemed logical that cows — like horses — would eat the seeds or seedlings of maple trees, thereby ingesting the toxins,” explains Zeyner. For the new study, the team examined samples from dairy farmers in northern Germany. Only milk provided directly from the farms was analysed. “We did not analyse samples from individual cows; instead, we sampled the milk from several cows which was stored in collection tanks,” says Zeyner.
The samples were analysed using a special form of mass spectrometry which can detect even tiny amounts of a substance. The result: “We detected hypoglycin A only in two samples of raw milk from the one of the farms whose pasture contained a single maple tree,” says Zeyner. The concentration of the substance was 17 and 69 micrograms per litre of milk. “These are low and widely varying concentrations. But considering that there was only one tree in the pasture and the sample came from a collection tank, it was surprising that we were able to detect anything at all,” explains Zeyner. The toxin could not be detected in any of the other samples.
“Our study is the first to show that cows appear to ingest parts of the sycamore maple containing the toxin, which is then transferred to their milk. Many other questions arise from this finding,” says the researcher in summary. It is still unclear, for example, how much toxin the cows have to ingest for there to be detectable traces in their milk. Follow-up studies will be needed to determine whether the substance is destroyed when the milk is processed or even whether this low concentration is a cause for concern, and how it can be prevented.
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The ability of stem cells to fix impaired functions of host tissues after transplantation has been a lifesaving breakthrough in treating previously incurable conditions. Much like a coin toss, however, the fate of the transplanted stem cells is unpredictable. They may choose self-renewal, grow into a different kind of tissue, or die.
Spermatogonial stem cells follow the same stochastic fate of unpredictability in outcomes. But a group of fertility scientists led by Hiroshima University’s Yoshiaki Nakamura discovered a new method that has favorably flipped the odds and successfully reversed male infertility in mice — showing great promise for future applications in regenerating human sperm after cancer treatment and repopulating threatened and endangered species. Results of their study are published in the journal Cell Stem Cell.
“Transplantation of spermatogonial stem cells promises a wealth of applications such as the treatment of infertility in men and the preservation of genetic diversity. Yet, currently, its inefficiency rules out the practical application of this technology,” Nakamura, assistant professor at the HU Graduate School of Integrated Sciences for Life, said.
“Our knowledge about the fate behavior of individual spermatogonial stem cells and their progenies following transplantation remains poorly developed, limiting the potential to develop new strategies to increase the currently low transplantation efficiencies,” he added.
Taking an up-close look at single-cell resolution, the international team of Japanese and British scientists tracked the fate of transplanted spermatogonial stem cells in mice. They implanted normal mouse sperm stem cells in infertile mice and found that only a tiny fraction repopulates in the long-term as working spermatogonia and the rest change into a different type of cell — a process called differentiation — or cease to carry out its function and die.
Using these insights, they developed a new method that can artificially tune the fate of the sperm stem cells to increase the likelihood of repopulation to a level where fertility is restored. They briefly introduced a retinoic acid synthesis inhibitor after transplantation, which temporarily prevented the donor sperm stem cells from undergoing differentiation. The chemical inhibitor helped orchestrate an outcome where the stem cells choose a fate of self-renewal.
“We demonstrated that repopulation efficiency of transplanted spermatogonial stem cells increased by tuning their stochastic fate,” Nakamura said, adding that the next step for their research is to confirm if their new strategy will also work for livestock and eventually humans.
“My final objective is to apply spermatogonial stem cell transplantation for the fertility of male individuals with cancer after chemotherapy or the preservation of genetic diversity in farm animals and rare or endangered wild animals,” he said.
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Carbon dioxide emissions in Los Angeles fell 33% in April of 2020 compared with previous years, as roads emptied and economic activity slowed due to the COVID-19 pandemic, according to a new study in Geophysical Research Letters. In the Washington, D.C./Baltimore region, emissions of carbon dioxide, or CO2, dropped by 34% during the same period.
The study was led by scientists at NASA’s Jet Propulsion Laboratory (JPL), the National Institute of Standards and Technology (NIST) and the University of Notre Dame.
While the emissions reductions are significant, the method that scientists used to measure them may have the greater long-term impact.
In both locations, scientists had previously installed networks of sensors on rooftops and towers to monitor the concentration of CO2 in the air. They used the data from those sensor networks to estimate the drop in emissions.
This might seem an obvious way to estimate emissions, but this is not how it’s usually done. Most cities estimate their emissions by tallying up the effects of activities that cause emissions, such as the number of vehicle miles traveled or the square footage of buildings heated and cooled. These are called “bottom up” methods because they are mostly based on activities on the ground.
This new study demonstrates that “top-down” methods, based on measuring the concentration of CO2 in the air, can produce reliable emissions estimates. Scientists were able to test those methods when emissions suddenly dropped due to COVID-19.

Type 1 diabetes, which arises when the pancreas doesn’t create enough insulin to control levels of glucose in the blood, is a disease that currently has no cure and is difficult for most patients to manage. Scientists at the Salk Institute are developing a promising approach for treating it: using stem cells to create insulin-producing cells (called beta cells) that could replace nonfunctional pancreatic cells.
In a study published on June 7, 2021, in the journal Nature Communications, the investigators reported that they have developed a new way to create beta cells that is much more efficient than previous methods. Additionally, when these beta cells were tested in a mouse model of type 1 diabetes, the animals’ blood sugar was brought under control within about two weeks.
“Stem cells are an extremely promising approach for developing many cell therapies, including better treatments for type 1 diabetes,” says Salk Professor Juan Carlos Izpisua Belmonte, the paper’s senior author. “This method for manufacturing large numbers of safe and functional beta cells is an important step forward.”
In the current work, the investigators started with human pluripotent stem cells (hPSCs). These cells, which can be derived from adult tissues (most often the skin), have the potential to become any kind of cell found in the adult body. Using various growth factors and chemicals, the investigators coaxed hPSCs into beta cells in a stepwise fashion that mimicked pancreatic development.
Producing beta cells from hPSCs in the lab is not new, but in the past the yields of these precious cells have been low. With existing methods, only about 10 to 40 percent of cells become beta cells. By comparison, techniques used to create nerve cells from hPSCs have yields of about 80 percent. Another issue is that if undifferentiated cells are left in the mix, they could eventually turn into another kind cell that would be unwanted.
“In order for beta cell-based treatments to eventually become a viable option for patients, it’s important to make these cells easier to manufacture,” says co-first author Haisong Liu, a former member of the Belmonte lab. “We need to find a way to optimize the process.”
To address the problem, the researchers took a stepwise approach to create beta cells. They identified several chemicals that are important for inducing hPSCs to become more specialized cells. They ultimately identified several cocktails of chemicals that resulted in beta cell yields of up to 80 percent.
They also looked at the ways in which these cells are grown in the lab. “Normally cells are grown on a flat plate, but we allowed them to grow in three dimensions,” says co-first author Ronghui Li, a postdoctoral fellow in the Belmonte lab. Growing the cells in this way creates more shared surface area between the cells and allows them to influence each other, just as they would during human development.
After the cells were created, they were transplanted into a mouse model of type 1 diabetes, The model mice had a modified immune system that would not reject transplanted human cells. “We found that within two weeks these mice had a reduction of their high blood sugar level into normal range,” says co-first author Hsin-Kai Liao, a staff researcher in the Belmonte lab. “The transplanted hPSC-derived beta cells were biologically functional.”
The researchers will continue to study this technique in the lab to further optimize the production of beta cells. More research is needed to assess safety issues before clinical trials can be initiated in humans. The investigators say the methods reported in this paper may also be useful for developing specialized cells to treat other diseases.
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The threat of antibiotic resistance rises as bacteria continue to evolve to foil even the most powerful modern drug treatments. By 2050, antibiotic resistant-bacteria threaten to claim more than 10 million lives as existing therapies prove ineffective.
Bacteriophage, or “phage,” have become a new source of hope against growing antibiotic resistance. Ignored for decades by western science, phages have become the subject of increasing research attention due to their capability to infect and kill bacterial threats.
A new project led by University of California San Diego Biological Sciences graduate student Joshua Borin, a member of Associate Professor Justin Meyer’s laboratory, has provided evidence that phages that undergo special evolutionary training increase their capacity to subdue bacteria. Like a boxer in training ahead of a title bout, pre-trained phages demonstrated they could delay the onset of bacterial resistance.
The study, which included contributions from researchers at the University of Haifa in Israel and the University of Texas at Austin, is published June 8 in the Proceedings of the National Academy of Sciences.
“Antibiotic resistance is inherently an evolutionary problem, so this paper describes a possible new solution as we run out of antibiotic drug options,” said Borin. “Using bacterial viruses that can adapt and evolve to the host bacteria that we want them to infect and kill is an old idea that is being revived. It’s the idea of the enemy of our enemy is our friend.”
The idea of using phages to combat bacterial infections goes back to the days prior to World War II. But as antibiotic drugs became the leading treatment for bacterial infections, phage research for therapeutic potential was largely forgotten. That mindset has changed in recent years as deadly bacteria continue to evolve to render many modern drugs ineffective.
Borin’s project was designed to train specialized phage to fight bacteria before they encounter their ultimate bacterial target. The study, conducted in laboratory flasks, demonstrated classic evolutionary and adaptational mechanisms at play. The bacteria, Meyer said, predictably moved to counter the phage attack. The difference was in preparation. Phages trained for 28 days, the study showed, were able to suppress bacteria 1,000 times more effectively and three- to eight-times longer than untrained phage.
“The trained phage had already experienced ways that the bacteria would try to dodge it,” said Meyer. “It had ‘learned’ in a genetic sense. It had already evolved mutations to help it counteract those moves that the bacteria were taking. We are using phage’s own improvement algorithm, evolution by natural selection, to regain its therapeutic potential and solve the problem of bacteria evolving resistance to yet another therapy.”
The researchers are now extending their findings to research how pre-trained phages perform on bacteria important in clinical settings, such as E. coli. They are also working to evaluate how well training methods work in animal models.
UC San Diego is a leader in phage research and clinical applications. In 2018 the university’s School of Medicine established the Center for Innovative Phage Applications and Therapeutics, the first dedicated phage therapy center in North America.
“We have prioritized antibiotics since they were developed and now that they are becoming less and less useful people are looking back to phage to use as therapeutics,” said Meyer. “More of us are looking into actually running the experiments necessary to understand the types of procedures and processes that can improve phage therapeutics.”
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Materials provided by University of California – San Diego. Original written by Mario Aguilera. Note: Content may be edited for style and length.