Washington: In multiple studies from eight cohorts across the United States, a group of researchers accelerated the collection of essential data to answer questions about the immune response needed for long-term protection against SARSCoV2.A description of the cohort, assays used, and event definitions were recently published in the American Society for Microbiology's open-access journal, mSphere.Longitudinal observation studies (studies that employ continuous or repeated measures to follow particular individuals over time) are essential to answer important questions on the durability and effectiveness of immune responses against SARS-CoV-2. Often individual cohorts have limited longitudinal data or participant numbers to draw robust conclusions. To overcome these limitations, harmonized yet independent cohorts were established in different geographic locations of the U.S. - the PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2) and SPARTA (SARS SeroPrevalence and Respiratory Tract Assessment) cohorts.These cohorts offer a nimble and rapid approach to stand up a network suitable to collect biospecimens and other data."We started the PARIS cohort at the Icahn School of Medicine at Mount Sinai because we wanted to know 3 things: how long antibody responses to SARS-CoV-2 last during infection, whether antibody responses protect against reinfection and how much antibody an individual needs to be protected," said senior study author Florian Krammer, Ph.D., a professor of Microbiology and Pathology at the Icahn School of Medicine at Mount Sinai."It is very important when you have an emerging virus to study the immune responses to the infection itself over time, to look at the protective effects of immune responses induced by infection, and also study what happens when people get vaccinated," added lead study author Viviana Simon, M.D., Ph.D., a professor of Microbiology, Infectious Diseases and Pathology at the Icahn School of Medicine at Mount Sinai.In the new study, to understand re-infection rates and correlates of protection for SARS-CoV-2, the researchers established 8 different longitudinal cohorts in 2020 under the umbrella of the PARIS /SPARTA studies. The cohorts included seropositive and seronegative participants at high risk for infection.The initial PARIS study focused on healthcare workers in New York City, one of the early epicentres of the pandemic in the U.S., but the other cohorts targeted not only healthcare workers but other populations including communities of colour, first responders and students.With the rapid SARS-CoV-2 vaccine rollouts starting in mid-December 2020 in the United States, many of the cohorts also now track immune responses to vaccination in individuals both seronegative and seropositive at the time of immunization. There were 8,741 participants in the 8 cohorts. In all 8 cohorts, the researchers followed individuals with and without COVID-19 by collecting data as well as biospecimens to measure immune responses (e.g., antibody responses to the spike protein of SARS-CoV-2) at least every 2 months."We saw that the antibody response in previously infected individuals was relatively stable, and they were protected from re-infection unless the new infection was the Omicron variant," said Dr. Krammer. The team studied how immune responses behaved in previously infected individuals versus those who hadn't yet been infected. The researchers showed that previously infected individuals mounted very rapid immune responses even after a single vaccine dose. "Vaccination boosts your protection and provides better immunity," said Dr. Krammer. —ANI

In multiple studies from eight cohorts across the United States, a group of researchers accelerated the collection of essential data to answer questions about the immune response needed for long-term protection against SARSCoV2.

Durability And Effectiveness Of Immune Response Against COVID-19: Study

Washington: &nbsp;A small molecule has been identified that blocks a key pathway in brain tumours, according to the scientists at the University of Michigan Rogel Cancer Center.However, there was a problem as to how to get the inhibitor through the bloodstream and into the brain to reach the tumour. In collaboration with multiple labs, the teams fabricated a nanoparticle to contain the inhibitor, and the results were even better than expected. Not only did the nanoparticles deliver the inhibitor to the tumour in mouse models, where the drug successfully turned on the immune system to eliminate cancer, but the process triggered immune memory so that a reintroduced tumour was also eliminated–a sign that this potential new approach could not only treat brain tumours but prevent or delay recurrences.“No one could get this molecule into the brain. It’s really a huge milestone. Outcomes for patients with glioma have not improved for the last 30 years,” said Maria G. Castro, PhD, R.C. Schneider Collegiate Professor of Neurosurgery at Michigan Medicine. Castro is the senior author of the study, published in ACS Nano.“Despite survival gains in many cancer types, glioma remains stubbornly challenging, with only 5% of patients living five years after their diagnosis,” said study author Pedro R. Lowenstein, M.D., PhD, Richard C. Schneider Collegiate Professor of Neurosurgery at Michigan Medicine.Gliomas are often resistant to traditional therapies, and the environment inside the tumour suppresses the immune system, rendering new immune-based therapies ineffective. Add to that the challenge of passing the blood-brain barrier, and it becomes even more difficult to deliver effective treatments to these tumours.The Castro-Lowenstein lab saw an opportunity. The small-molecule inhibitor AMD3100 was developed to block the action of CXCR12, a cytokine released by the glioma cells that build up a shield around the immune system, preventing it from firing up against the invading tumour. Researchers showed in mouse models of glioma that AMD3100 prevented CXCR12 from binding with immune-suppressive myeloid cells. By disarming these cells, the immune system remains intact and can attack the tumour cells. But AMD3100 was having trouble getting to the tumour. The drug did not travel well through the bloodstream, and it did not pass the blood-brain barrier, a key issue with getting drugs into the brain. The Castro-Lowenstein lab collaborated with Joerg Lahann, PhD, Wolfgang Pauli Collegiate Professor of Chemical Engineering at the U-M College of Engineering, to create protein-based nanoparticles to encapsulate the inhibitor, in the hopes of helping it pass through the bloodstream. Castro also connected with Anuska V. Andjelkovic, M.D., Ph.D., professor of pathology and research professor of neurosurgery at Michigan Medicine, whose research focuses on the blood-brain barrier. They noted that glioma tumours create abnormal blood vessels, interfering with normal blood flow. The researchers injected AMD3100-loaded nanoparticles into mice with gliomas. The nanoparticles contained a peptide on the surface that binds to a protein found mostly on the brain tumour cells. As the nanoparticles travelled through the bloodstream toward the tumour, they released AMD3100, which restored the integrity of the blood vessels. The nanoparticles could then reach their target, where they released the drug, thus blocking the entry of the immune-suppressive myeloid cells into the tumour mass. This allowed the immune cells to kill the tumour and delay its progression. “If you don’t have blood flow, nothing will get to your target. That’s why tumours are so smart. But AMD3100 restores the conduits, which is what allows the nanoparticles to reach the tumour,” Castro said.Further studies in mice and patient cell lines demonstrated that coupling the AMD3100 nanoparticle with radiation therapy enhanced the effect beyond either the nanoparticle or radiation alone.Among the mice whose tumours were eliminated, the researchers then reintroduced the tumour, simulating a recurrence. Without any additional therapy, 60% of mice remained cancer-free. This suggests that, like a vaccine, AMD3100 created immune memory, enabling the immune system to recognize and destroy the reintroduced cells. While it prevented a recurrence in mice, Castro said it bodes well for at least delaying recurrence in people. “Every glioma recurs. It’s very important for glioma therapy to have this immunological memory,” Castro said. Initial tests showed little to no impact on liver, kidney or heart function and normal blood counts in the mice after treatment. The nanoparticle has a similar base as ones that have been previously tested in humans and shown to be safe. Additional safety testing is necessary before moving to a clinical trial.—ANI

 A small molecule has been identified that blocks a key pathway in brain tumours, according to the scientists at the University of Michigan Rogel Cancer Center.

Study: Outsmarting brain cancer, nanoparticle and inhibitor trigger the immune system

Washington: A small molecule has been identified that blocks a key pathway in brain tumours, according to the scientists at the University of Michigan Rogel Cancer Center.However, there was a problem as to how to get the inhibitor through the bloodstream and into the brain to reach the tumour. In collaboration with multiple labs, the teams fabricated a nanoparticle to contain the inhibitor, and the results were even better than expected.Not only did the nanoparticles deliver the inhibitor to the tumour in mouse models, where the drug successfully turned on the immune system to eliminate cancer, but the process triggered immune memory so that a reintroduced tumour was also eliminated--a sign that this potential new approach could not only treat brain tumours but prevent or delay recurrences."No one could get this molecule into the brain. It's really a huge milestone. Outcomes for patients with glioma have not improved for the last 30 years," said Maria G. Castro, PhD, R.C. Schneider Collegiate Professor of Neurosurgery at Michigan Medicine. Castro is the senior author of the study, published in ACS Nano."Despite survival gains in many cancer types, glioma remains stubbornly challenging, with only 5% of patients living five years after their diagnosis," said study author Pedro R. Lowenstein, M.D., PhD, Richard C. Schneider Collegiate Professor of Neurosurgery at Michigan Medicine.Gliomas are often resistant to traditional therapies, and the environment inside the tumour suppresses the immune system, rendering new immune-based therapies ineffective. Add to that the challenge of passing the blood-brain barrier, and it becomes even more difficult to deliver effective treatments to these tumours.The Castro-Lowenstein lab saw an opportunity. The small-molecule inhibitor AMD3100 was developed to block the action of CXCR12, a cytokine released by the glioma cells that build up a shield around the immune system, preventing it from firing up against the invading tumour. Researchers showed in mouse models of glioma that AMD3100 prevented CXCR12 from binding with immune-suppressive myeloid cells. By disarming these cells, the immune system remains intact and can attack the tumour cells.But AMD3100 was having trouble getting to the tumour. The drug did not travel well through the bloodstream, and it did not pass the blood-brain barrier, a key issue with getting drugs into the brain.The Castro-Lowenstein lab collaborated with Joerg Lahann, PhD, Wolfgang Pauli Collegiate Professor of Chemical Engineering at the U-M College of Engineering, to create protein-based nanoparticles to encapsulate the inhibitor, in the hopes of helping it pass through the bloodstream.Castro also connected with Anuska V. Andjelkovic, M.D., Ph.D., professor of pathology and research professor of neurosurgery at Michigan Medicine, whose research focuses on the blood-brain barrier. They noted that glioma tumours create abnormal blood vessels, interfering with normal blood flow.The researchers injected AMD3100-loaded nanoparticles into mice with gliomas. The nanoparticles contained a peptide on the surface that binds to a protein found mostly on the brain tumour cells. As the nanoparticles travelled through the bloodstream toward the tumour, they released AMD3100, which restored the integrity of the blood vessels. The nanoparticles could then reach their target, where they released the drug, thus blocking the entry of the immune-suppressive myeloid cells into the tumour mass. This allowed the immune cells to kill the tumour and delay its progression."If you don't have blood flow, nothing will get to your target. That's why tumours are so smart. But AMD3100 restores the conduits, which is what allows the nanoparticles to reach the tumour," Castro said.Further studies in mice and patient cell lines demonstrated that coupling the AMD3100 nanoparticle with radiation therapy enhanced the effect beyond either the nanoparticle or radiation alone. Among the mice whose tumours were eliminated, the researchers then reintroduced the tumour, simulating a recurrence. Without any additional therapy, 60% of mice remained cancer-free. This suggests that, like a vaccine, AMD3100 created immune memory, enabling the immune system to recognize and destroy the reintroduced cells. While it prevented a recurrence in mice, Castro said it bodes well for at least delaying recurrence in people."Every glioma recurs. It's very important for glioma therapy to have this immunological memory," Castro said. Initial tests showed little to no impact on liver, kidney or heart function and normal blood counts in the mice after treatment. The nanoparticle has a similar base as ones that have been previously tested in humans and shown to be safe. Additional safety testing is necessary before moving to a clinical trial. —ANI

A small molecule has been identified that blocks a key pathway in brain tumours, according to the scientists at the University of Michigan Rogel Cancer Center.

Study: Outsmarting Brain Cancer, Nanoparticle And Inhibitor Trigger The Immune System

South Korea (Asia): According to research, 'STING', which is an innate immune regulatory protein has the ability to promote tumour immunoreactivity and immune cell penetration into the tumour microenvironment (TME).The results of this study were published in the latest issue of "The Journal of Medical Chemistry," an international journal covering the field of pharmaceutical chemistry, and were selected to be presented as the supplementary cover for the journal.Innovations in cancer immunotherapy have achieved clinical success by considerably increasing the survival rate of patients undergoing cancer treatment. However, there still exists an unmet medical need due to the low response rate to checkpoint inhibitors caused by the low immune reactivity of cancer cells in "cold" tumours. In their efforts to turn "cold" tumours into "hot" tumours, many global pharmaceutical companies have been focusing on utilizing the innate immune regulatory protein known as STING to increase the immunoreactivity of tumours and the infiltration of immune cells into the tumour microenvironment (TME). However, since clinical trials on the first STING agonist, ADU-S100, were suspended in 2020, there is an urgent need to develop new STING activators.Under these circumstances, a research team led by Dr Sanghee Lee of the Brain Science Institute at the Korea Institute of Science and Technology (KIST; President: Seok-Jin Yoon), and Dr Hyejin Kim of the Infectious Diseases Therapeutic Research Center at the Korea Research Institute of Chemical Technology (KRICT; President: Mihye Yi) announced the development of a new small-molecule STING agonist.Once the STING agonist was stimulated by a compound, it induced the secretion of cytokines such as interferons (IFNs) and activated an innate immune response mediated by T cells. The activated immune system altered the immune phenotype of the tumour, turning it from "cold" with low reactivity to T cells to "hot" with high reactivity, leading to the recruitment of T cells in the TME. In this study, compound administration effectively inhibited the growth of cancer cells in mice models. In particular, 20% of the treated group was found to be tumour-free as a result of the complete elimination of their tumours. Furthermore, immunological memory suppressed the growth of recurrent tumours without the need for additional drug administration. Ultimately, no tumour growth was observed in the tumour-free group after the first treatment. Most of the existing STING agonists were subjected to intratumoral administration, which limited the broad application of cancer treatment, whereas the compound in this study was able to be administered by intravenous injection. In terms of further drug development, this agent is also able to be applied to combination cancer therapies and current standard treatments, such as radiation therapy, chemotherapy, and monotherapy.Dr Lee stated, "Everyone dreams of vanquishing cancer; however, the development of cancer immunotherapeutics for ailments such as brain tumours is still limited. We hope that this study can provide the seeds for new therapeutic strategies for cancers where immunotherapy has had limited application."KIST was established in 1966 as the first government-funded research institute in Korea to establish a national development strategy based on science and technology and disseminate various industrial technologies to promote the development of major industries. KIST is now elevating the status of Korean science and technology through the pursuit of world-leading innovative research and development.This study was supported by the Ministry of Science and ICT (Minister: Dr Jong-Ho Lee), KIST Institutional Program, KRICT Institutional Program, NRF Young Researcher Program, and AI New Drug Development Project. —ANI

According to research, 'STING', which is an innate immune regulatory protein has the ability to promote tumour immunoreactivity and immune cell penetration into the tumour microenvironment (TME).

Cancer Treatment With The Ability To Alter Tumour Immunophenotypes: Research

Washington: According to the researchers at the Tokyo Medical and Dental University, schizophrenia is a disorder that affects how people act, think, and perceive reality. It is often very difficult to treat because it has many different causes and symptoms.In a study published last month in Cell Reports Medicine, researchers from Tokyo Medical and Dental University (TMDU) have identified an autoantibody -- a protein that is produced by the immune system to attach to a specific substance from the individual's own body, rather than to a foreign substance like a virus or bacteria -- in some patients with schizophrenia.Notably, they also found that this autoantibody caused schizophrenia-like behaviors and changes in the brain when they injected it into mice.When considering possible autoantibodies that might cause schizophrenia, the research team had a specific protein in mind. Previous research has suggested that neural cell adhesion molecule (NCAM1), which helps cells in the brain talk to one another via specialized connections known as synapses, may have a role in the development of schizophrenia."We decided to look for autoantibodies against NCAM1 in around 200 healthy controls and 200 patients with schizophrenia," explains lead author of the study Hiroki Shiwaku. "We only found these autoantibodies in 12 patients, suggesting that they may be associated with the disorder in just a small subset of schizophrenia cases."The research team didn't stop there -- they wanted to know whether these autoantibodies could cause any changes that commonly occur in schizophrenia, so they purified autoantibodies from some of the patients and injected them into the brains of mice."The results were impressive," says Hidehiko Takahashi, senior author. "Even though the mice only had these autoantibodies in their brains for a short time, they had changes in their behavior and synapses that were similar to what is seen in humans with schizophrenia."Specifically, mice with the patient autoantibodies had cognitive impairment and changes in their regulation of the startle reflex, which are both seen in other animal models of schizophrenia. They also had fewer synapses and dendritic spines, which are structures that are important for the connections between brain cells, and are also affected in schizophrenia. Given that schizophrenia can present very differently among patients and is often resistant to treatment, the results of this study are promising. If schizophrenia is indeed caused by autoantibodies against NCAM1 in some patients, this will lead to important improvements in their diagnosis and treatment. —ANI

 According to the researchers at the Tokyo Medical and Dental University, schizophrenia is a disorder that affects how people act, think, and perceive reality. It is often very difficult to treat because it has many different causes and symptoms.

Researchers Found New Evidence For Autoimmune Cause Of Schizophrenia

Columbia: For a long time, researchers have worked to understand the immune reactions that take place in the human body during various illnesses, such as cancer and inflammatory disorders.
Emma Teixeiro, an associate professor in the MU School of Medicine, and her group recently examined how immunological memory, which the body's immune system retains after an infection or vaccination and helps prevent reinfection, gets generated and maintained, as well as the role inflammation plays in forming that immunological memory.
"Our immune system defends us from disease, but it is a very complicated system with many interactions occurring, and if things get dysregulated, it may actually play a role in causing disease," said Teixeiro, who works in the NextGen Precision Health Institute on MU's campus. "So, our research focuses on better understanding how these immune responses can be generated and controlled, specifically by looking at the critical role T cells play, as T cells help protect the body from infection and may play a role in attacking cancer."
Using a mouse model, the researchers created various strains of pathogenic bacteria that increased levels of inflammation through the stimulator of interferon genes - or STING - proteins inside of T cells. While many scientists assumed this increase in inflammation would result in a stronger immune response and therefore stronger immunological memory, Teixeiro and her team found the opposite: immunological memory was reduced.
"Some scientists in the field believe STING activation may be targeted to improve cancer vaccines or immunotherapies, so gaining a basic understanding of all the interacting mechanisms at play is critical to reduce the chances of unintended consequences or harmful side effects," Teixeiro said. "We want to better understand how to regulate immunological memory, which has implications for potential vaccines or immunotherapies that trigger T cells in a way that hopefully boosts long-term memory, so our bodies are protected from disease over time."
While her research is fundamental in nature, Teixeiro's findings have the potential to contribute to the development of more effective treatments to help patients suffering with cancer, chronic obstructive pulmonary disease (COPD), STING-associated vasculopathy with onset in infancy (SAVI), asthma and other chronic inflammatory syndromes.
"The pursuit of knowledge is what drives my curiosity as a scientist," Teixeiro said. "While there are still more questions to answer, this research is a small step in the right direction, and I am proud to be a part of it." "STING controls T cell memory fitness during infection through T cell intrinsic and Indoleamine-pyrrole 2,3-dioxygenase (IDO) dependent mechanisms" was recently published in PNAS. Coauthors on the study include Michael Quaney, Curtis Pritzl, Rebecca Newth, Karin Knudson, Vikas Saxena, Caitlyn Guldenpfennig, Diana Gil, Chris Rae, Peter Lauer, Mark Daniels and Dezzarae Luera. —ANI

For a long time, researchers have worked to understand the immune reactions that take place in the human body during various illnesses, such as cancer and inflammatory disorders.

Regulating Immunological Memory Help Immune System Fight Disease: Researchers 

Tokyo: Researchers have found differences between men and women in a type of immune cell and in the way antibodies are made in response to COVID-19. This may explain why men are more likely to get sick from the disease.
The cellular basis for the increased risk of COVID-19 infection in males remains unclear.
The researchers at Osaka University in Japan have now found sex-specific changes in a kind of immune cell called regulatory T cells, or "Treg cells," and in the production of proteins called antibodies.—Inputs from Agencies

Researchers have found differences between men and women in a type of immune cell and in the way antibodies are made in response to COVID-19. This may explain why men are more likely to get sick from the disease

Why men are at higher risk from COVID-19 decoded

Washington: In a new study, the University of Iowa biologists have lain out a chain of events that can cause seizures, the most common manifestation of epilepsy, to worsen.
The sequence begins when oxidative stress in the body causes the brain's immune system to react. That activation by the brain's resident immune cells (called glia) triggers more severe seizures.
The findings are important because it's the first time the brain immune system-epilepsy link has been experimentally proved. That advance should yield more precise testing and more effective medications to treat the condition.
The study, 'Downregulation of oxidative stress-mediated glial innate immune response suppresses seizures in a fly epilepsy model', was published in the journal Cell Reports.
"We have provided genetic proof that both oxidative stress and activation of the brain immune system make epilepsy worse," says John Manak, professor in the Department of Biology and Stead Family Department of Pediatrics at Iowa and the study's corresponding author. "This is hugely significant because our data suggest that we can now repurpose exceedingly well-tolerated anti-inflammatory compounds as well as perhaps antioxidants to help control epilepsy progression."
Epilepsy affects 3.4 million people--the vast majority being adults--in the United States, according to the U.S. Centers for Disease Control and Prevention. Worldwide, an estimated 5 million people are diagnosed with epilepsy each year, according to the World Health Organization.
The researchers clinched the brain-epilepsy connection in experiments using fruit flies. One reason they chose the insects is because fruit flies and humans share a common ancestral gene, called prickle, that when mutated, leads to seizures. The prickle gene's involvement in epileptic seizures was determined by, among others, Alex Bassuk, pediatric neurologist and chair of the Stead Family Department of Pediatrics at Iowa, who published findings in 2008 and is a co-author on this study.
Manak's team also chose fruit flies for their experiments because flies, unlike humans and other vertebrates, have a single, primitive disease response mechanism, called the innate immune system, that is utilized by glial cells in the brain. Vertebrates also have an innate immune system, but that is complemented by an adaptive immune system that involves an army of immune cells with stored "memories" of past, invasive pathogens. The fruit fly's lone innate immune system meant the researchers could concentrate exclusively on the brain innate immune system-epilepsy connection.
The researchers identified all genes that became expressed in fly brains with seizures (triggered by the mutated prickle gene) compared with those with no seizures. They identified two classes of upregulated genes associated with the seizure-laden flies: immune response genes and those involved in mitigating oxidative stress.
In further experiments with fruit flies, the researchers turned off the innate immune system in the brain glia. That action reduced neuronal cell death, which in turn suppressed seizures.
In another set of experiments with flies, the researchers tested the oxidative stress link by expressing the brain's SOD1 gene, which is known to cleanse cells of reactive oxygen species caused by oxidative stress. When this gene was activated in the fruit fly brains, the flies' innate immune system response was lowered, and seizures were reduced.
"In one fell swoop, we have identified a pathway starting at increased oxidative stress leading to activation of the innate immune system, which leads to neuronal cell death, which, in turn, causes exacerbation of seizures," says Manak, who calls the study one of the highlights of his almost 40-year career as a biologist. "And when I say exacerbation of seizures, I mean progressive epilepsy, which are epilepsies that get worse over time."
The results mean the flies can be used to directly test which anti-inflammatory drugs or antioxidants would be most effective in treating epileptic seizures. Until now, doctors had only limited evidence that a small number of anti-inflammatory or antioxidant medications had seizure-suppressive characteristics in some contexts, but no direct proof connecting oxidative stress and innate immune system activation with epilepsy. Moreover, approximately one-third of epilepsy patients do not respond well to currently available therapies, and two-thirds of patients have adverse side effects to the medications, according to the study's authors.
"Not every anti-inflammatory or antioxidant compound is going to effectively treat epilepsy," Manak explains. "We now have the perfect model with our flies to screen through a significant number of anti-inflammatory and antioxidant compounds. We can then elevate any promising drugs to mouse models, and then potentially human trials."&nbsp;
&nbsp;—ANI

In a new study, the University of Iowa biologists have lain out a chain of events that can cause seizures, the most common manifestation of epilepsy, to worsen.

Researchers Explore How Brain's Immune System Worsens Epilepsy

Washington: According to a new study by the Icahn School of Medicine at Mount Sinai, fasting may be detrimental to fighting off infection and could lead to an increased risk of heart disease.
The research, which focused on mouse models, is among the first to show that skipping meals triggers a response in the brain that negatively affects immune cells. The results that focus on breakfast were published in the issue of Immunity and could lead to a better understanding of how chronic fasting may affect the body long term.
"There is a growing awareness that fasting is healthy, and there is indeed abundant evidence for the benefits of fasting. Our study provides a word of caution as it suggests that there may also be a cost to fasting that carries a health risk," says lead author Filip Swirski, PhD, Director of the Cardiovascular Research Institute at Icahn Mount Sinai. "This is a mechanistic study delving into some of the fundamental biology relevant to fasting. The study shows that there is a conversation between the nervous and immune systems."
Researchers aimed to better understand how fasting -- from a relatively short fast of only a few hours to a more severe fast of 24 hours -- affects the immune system. They analyzed two groups of mice. One group ate breakfast right after waking up (breakfast is their largest meal of the day), and the other group had no breakfast. Researchers collected blood samples in both groups when mice woke up (baseline), then four hours later, and eight hours later.
When examining the blood work, researchers noticed a distinct difference in the fasting group. Specifically, the researchers saw a difference in the number of monocytes, which are white blood cells that are made in the bone marrow and travel through the body, where they play many critical roles, from fighting infections to heart disease to cancer.
At baseline, all mice had the same amount of monocytes. But after four hours, monocytes in mice from the fasting group were dramatically affected. Researchers found 90 per cent of these cells disappeared from the bloodstream, and the number further declined at eight hours. Meanwhile, monocytes in the non-fasting group were unaffected.
In fasting mice, researchers discovered the monocytes travelled back to the bone marrow to hibernate. Concurrently, the production of new cells in the bone marrow diminished. The monocytes in the bone marrow--which typically have a short lifespan--significantly changed. They survived longer as a consequence of staying in the bone marrow and aged differently than the monocytes that stayed in the blood.
The researchers continued to fast mice for up to 24 hours and then reintroduced food. The cells hiding in the bone marrow surged back into the bloodstream within a few hours. This surge led to a heightened level of inflammation. Instead of protecting against infection, these altered monocytes were more inflammatory, making the body less resistant to fighting infection.
This study is among the first to make the connection between the brain and these immune cells during fasting. Researchers found that specific regions in the brain controlled the monocyte response during fasting. This study demonstrated that fasting elicits a stress response in the brain--that's what makes people "hangry" (feeling hungry and angry) --and this instantly triggers a large-scale migration of these white blood cells from the blood to the bone marrow, and then back to the bloodstream shortly after a food is reintroduced.
Dr Swirski emphasized that while there is also evidence of the metabolic benefits of fasting, this new study is a useful advance in the full understanding of the body's mechanisms.
"The study shows that, on the one hand, fasting reduces the number of circulating monocytes, which one might think is a good thing, as these cells are important components of inflammation. On the other hand, the reintroduction of food creates a surge of monocytes flooding back into the blood, which can be problematic. Fasting, therefore regulates this pool in ways that are not always beneficial to the body's capacity to respond to a challenge such as an infection," explains Dr Swirski. "Because these cells are so important to other diseases like heart disease or cancer, understanding how their function is controlled is critical." —ANI

According to a new study by the Icahn School of Medicine at Mount Sinai, fasting may be detrimental to fighting off infection and could lead to an increased risk of heart disease.

Skipping Breakfast Can Compromise Immune System: Study

Charlottesville: According to recent research, the immune system's ability to respond to spinal cord injury reduces with age, but it also suggests possible strategies to improve that response and hasten patient recovery. The new results provide light on how the immune system responds to spinal cord injury and why that response becomes dulled over time. Furthermore, it demonstrates that the membranes surrounding the spinal cord play a significant role in establishing the immune response to spinal-cord damage. With this knowledge, clinicians may one day be able to boost the body's natural immune response to enhance patient outcomes, particularly in the elderly. "Recently, it has been reported more aging individuals experience spinal cord injuries. Our findings suggest in aging, there is an impairment in how the immune response is initiated and resolved compared to young," said researcher Andrea Francesca M. Salvador, who just received her PhD from the University of Virginia School of Medicine. "Hopefully, our results can help identify points of intervention and druggable targets that can improve recovery and address long-term consequences of injury such as pain." Spinal-cord injuries can have devastating, lifelong effects, leaving patients unable to move, unable to control their bowels or suffering pain, sexual dysfunction or uncontrollable spasms, depending on the severity and location of the injury. Better understanding how the body responds to spinal-cord injuries is an important step in developing better ways to treat them. The new findings are the latest from the lab of Jonathan Kipnis, PhD, who made a stunning discovery at UVA in 2015 that the brain was connected to the immune system by vessels long thought not to exist. Prior to this game-changing revelation, the brain had been held to be essentially walled off from the immune system. The discovery of the unknown vessels in the membranes, or meninges, surrounding the brain rewrote textbooks and opened a whole new frontier in neurological research. Today, "neuroimmunology," or the study of the nervous system's relationship to the immune system, is one of the hottest areas of neuroscience research, and it is poised to transform our understanding of - and ability to treat - a vast array of neurological diseases. Now Salvador, Kipnis and their collaborators have determined that the meninges surrounding the spinal cord play an essential role in the immune response to spinal-cord injury. They discovered, for example, that previously unknown meningeal lymphatic "patches" form above the site of spinal-cord injuries. More research is needed to determine exactly what these structures do, but their formation speaks to an important role for the spinal-cord meninges in the immune response to injury. Further, Salvador and her collaborators quantified how immune cells respond to spinal-cord injuries. They found that this response was much stronger in young lab mice than in older ones, suggesting that scientists may be able to target certain immune cells to improve recovery after spinal-cord injuries. —ANI Together, the findings identify the spinal-cord meninges - and their interactions with other components of the central nervous system - as exciting new areas for researchers to explore as they seek to better understand the body's complex response to spinal-cord injuries. "This is an exciting finding and one which may indeed lead to new therapeutic approaches for spinal cord-injury patients," said Kipnis, now a professor at Washington University School of Medicine in St. Louis and director of its Brain Immunology and Glia Center (BIG Center). "We are now collaborating with clinicians in a hope to better understand what is happening in human patients and how our findings could be translated to make a real difference." —ANI

 According to recent research, the immune system's ability to respond to spinal cord injury reduces with age

How Immune System Detection Benefit Spinal Cord Injuries: Researchers 

New York: Researchers have found a human immune system 'tripwire' that detects various viruses, including SARS-Cov-2, which cause Covid-19. The study, published in the journal PLOS Biology, described a previously unknown inflammasome immune protein known as CARD8. Inflammasomes make up an intricate system of molecular sensors that our bodies use to sound an alarm when an infection occurs. However, the mechanisms behind these sensors, which initiate responses to threats such as invading pathogens, and how they operate has been an area of intrigue for immunologists. The study showed that CARD8 functions differently among various species and even varies between individuals in the human population. The findings resulted from a series of experiments across human cell lines and an analysis of CARD8 genetic variation in mammalian species. "In a version of CARD8, we found that some humans have lost the ability to sense coronavirus infections based on a single genetic difference but have gained the ability to sense viruses in a different family, the enteroviruses -- which includes rhinovirus (common cold) and poliovirus," said Matt Daugherty, Associate Professor in the Department of Molecular Biology at the University of Washington. "So that means it's an evolutionary tradeoff and CARD8 diversity in humans impacts which viruses can be sensed and which ones cannot." The research team found that the bat version of CARD8 is not able to sense coronaviruses. This could explain how coronaviruses are able to infect bats so easily and become a virus "reservoir." The findings provide evidence that CARD8 has evolved substantially across different species of mammals and individual humans. "Our findings establish CARD8 as a rapidly evolving, polymorphic, innate immune sensor of positive-sense RNA viruses." Daugherty said researchers have only found the tip of the iceberg in terms of the way immune sensors sound the alarm about pathogens and infection. "It's amazing to see this evolutionary balance of one virus to another going from sensing to not sensing -- it's mind-blowing," said Daugherty. More studies are needed to thoroughly determine CARD8's role in the severity of Covid-19 infections and long Covid symptoms. "It is tempting to speculate that diminished CARD8 inflammasome activation may be a contributing factor to variation in Covid-19 disease outcomes, and more generally for other human pathogenic coronavirus and picornavirus infections," the researchers said. —IAN

Researchers have found a human immune system 'tripwire' that detects various viruses, including SARS-Cov-2, which cause Covid-19

How Human Immune System Detects Covid

La Jolla (California): With its complicated network of proteins, cells, and organs, the immune system guards the body against intruders like bacteria, viruses, or tumours. Cytotoxic T cells, specialised immune cells that destroy malignant or infected cells in our bodies, can transform into transient effector cells. After an infection, a tiny percentage of those effector cells survive and develop into memory cells with a longer lifespan. These cells "remember" infections and react when they recur. The factors that cause cytotoxic T cells to develop into these effector and memory T cell subtypes, however, are not well understood. Susan Kaech, a professor at the Salk Institute, and Diana Hargreaves, an associate professor, have now shown that a protein complex called cBAF may open or shut genetic "doors" that regulate T cell destiny. The research, which will be released in Immunity on June 13, 2023, sheds light on how T cells respond to and recall infections and opens the door to the creation of more potent vaccinations and cancer treatments. "We've shown how T cells transform into specialized subtypes during an infection and what happens when they mess up the genetic blueprint. Without this genetic blueprint, T cells may not be able to resolve or remember infections, or could possibly become cancerous, like we see in T cell lymphoma," said Kaech, senior and co-corresponding author, director of the NOMIS Center for Immunobiology and Microbial Pathogenesis, and holder of the NOMIS Chair. "Finding that the cBAF protein complex is essential in creating different T cell subtypes opens up new questions, like can we control this process to optimize immune cell function for cancer therapeutics?" The question of how cytotoxic T cells develop into effector and memory T cells can be answered by looking at how they are created--a process that relies on genetic instructions contained in chromatin. Chromatin is composed of a mixture of genetic code (DNA) that works as instructions, as well as proteins and RNA that regulate and protect those instructions. Rearranging chromatin within a cell exposes or conceals different sections of genetic code, in turn altering the available instructions. Once instructions are available, proteins called transcription factors determine if and how often they are read. The researchers knew that chromatin works like scaffolding--protecting the genetic code within and shielding it from transcription factors. For transcription factors to access those instructions, they likely need help from chromatin-remodeling cBAF, which can signal proteins and RNA to reveal genetic code for transcription factors. "Chromatin remodeling is essential in determining the identities of cells," says co-first author Bryan McDonald, a graduate student in the Kaech lab. "In other cell types, the chromatin remodeling complex cBAF was known to play a major role in cellular differentiation. We wanted to know if cBAF was important for cytotoxic T cell differentiation, too." The cBAF complex is made up of many subunits, including ARID1A. To explore the role of ARID1A on chromatin remodeling in T cells, the team examined T cells with and without ARID1A subunits in mice. After a week-long viral infection (to instigate the T cell immune response), the researchers looked for changes in chromatin structure, location of proteins, and genetic code accessibility. "The chromatin landscape evolved immensely over the course of the infection," said co-first author Brent Chick, a graduate student in the Hargreaves lab. "cBAF complexes bearing the ARID1A subunit were crucial in rearranging chromatin so transcription factors could access the genetic code that instructs the development of different T cell subtypes with specialized functions." Without ARID1A, the cytotoxic T cells could not turn into the short-lived, rapid-response effector subtype. The loss of ARID1A did not prevent the cytotoxic T cells from turning into their longer-lived memory subtype, but the memory cells made without ARID1A were not as effective at responding to a viral reinfection. Finally, the formation of memory T cells that reside in organs, like the lungs or small intestine, was dependent on ARID1A. Without ARID1A, tissue-resident memory T cells could not develop at all. ARID1A was the key player, as the team suspected. And the mechanism was now clear--during infections, cBAF complexes with ARID1A open different chromatin "doors" to reveal genetic code to transcription factors, which then determine the fate of the cytotoxic T cells. Establishing this novel mechanism paves the way for investigation into how chromatin remodeling, genetic code, and transcription factors together contribute to a successful immune system response. "Our research demonstrates that removing ARID1A from the immune response equation may greatly damage our ability to fight infection," says Hargreaves, co-corresponding author and holder of the Richard Heyman and Anne Daigle Endowed Developmental Chair. "I hope that our findings inspire new questions in infectious disease and cancer research--and that we have demonstrated the value of asking those questions collaboratively." —ANI

With its complicated network of proteins, cells, and organs, the immune system guards the body against intruders like bacteria

Study Gives More Insight Into Development Of Infection-Fighting Immune Cells

Washington: There is growing evidence that illnesses are more likely to affect astronauts in space. For instance, respiratory and non-respiratory illnesses are rather prevalent among astronauts on board the International Space Station (ISS), as well as skin rashes. Additionally, it is known that astronauts shed more live viral particles, including as Epstein-Barr virus, varicella-zoster, herpes-simplex-1, and CMV. These findings imply that space flight may compromise our immune system. “Here we show that the expression of many genes related to immune functions rapidly decreases when astronauts reach space, while the opposite happens when they return to Earth after six months aboard the ISS,” said Dr Odette Laneuville, an associate professor at the Department of Biology of the University of Ottawa, leading author of a new study in Frontiers in Immunology. The research was funded by the Canadian Space Agency. Three women and 11 men who were part of a cohort of 14 astronauts who spent between 4.5 and 6.5 months living on board the International Space Station (ISS) between 2015 and 2019 were evaluated for their gene expression in leukocytes (white blood cells). Four millilitres of blood were taken from each astronaut ten times: once before takeoff, four times during flight, and five times after landing to isolate leukocytes. 15,410 genes were found to be differentially expressed in leukocytes. Among these genes, the researchers identified two clusters, with 247 and 29 genes respectively, which changed their expression in tandem along the studied timeline. Genes in the first cluster were dialed down when reaching space and back up when returning to Earth, while genes in the second followed the opposite pattern. Both clusters mostly consisted of genes that code for proteins, but with a difference: their predominant function was related to immunity for the genes in the first cluster, and to cellular structures and functions for the second. These results suggest that when someone travels to space, these changes in gene expression cause a rapid decrease in the strength of their immune system. “A weaker immunity increases the risk of infectious diseases, limiting astronauts’ ability to perform their demanding missions in space. If an infection or an immune-related condition was to evolve to a severe state requiring medical care, astronauts while in space would have limited access to care, medication, or evacuation” said Dr Guy Trudel, a rehabilitation physician and researcher at The Ottawa Hospital and professor at the Department of Cellular and Molecular Medicine of the University of Ottawa. But there is a silver lining to this cloud: the data showed that most genes in either cluster returned to their pre-flight level of expression within one year after return on Earth, and typically much sooner – on average, after a few weeks. These results suggest that returning astronauts run an elevated risk of infection for at least one month after landing back on Earth. In contrast, the authors don’t yet know how long it takes before immune resistance is fully back to its pre-flight strength: the length of this period is likely to depend on age, sex, genetic differences, and childhood exposure to pathogens. The authors hypothesized that the change in gene expression of leukocytes under microgravity is triggered by ‘fluid shift’, where blood plasma is redistributed from the lower to the upper part of the body, including the lymphatic system. This causes a reduction in plasma volume by between 10% and 15% within the first few days in space. Fluid shift is known to be accompanied by large-scale physiological adaptations, apparently including altered gene expression. “The next question is how to apply our findings to guide the design of countermeasures that will prevent immune suppression while in space in particular for long duration flight,” said Laneuville. “The health of astronauts while in space, especially during long missions, would benefit from detecting both immune dysfunction and sub-clinical inflammation. Early detection provides opportunities for intervention, with the aim to prevent a progression towards severe symptoms.” —ANI

There is growing evidence that illnesses are more likely to affect astronauts in space. For instance

Space Travel May Alter Gene Expression, Weaken Immune System: Study

Cambridge: Cambridge scientists have discovered a blood pattern that could help predict how well an individual will respond to immunisations. The study, which was published in Nature Communications, could explain why, even within susceptible patient groups, some people respond better to immunisations than others. During the COVID-19 pandemic, it has become clear that some patients are better protected by vaccination than others. Many studies have shown that SARS-CoV-2 vaccines are less effective in people with weakened immune systems, but also that this effect is not uniform. Vaccination involves priming the immune system to look for - and get rid of - invading pathogens, such as viruses and bacteria. In part, this involves stimulating the production of antibodies uniquely programmed to identify a particular invader. These antibodies are themselves produced by a type of immune cell known as a B cell. One specific subset of B cells is known as age-associated B cells (ABCs). While, on average, less than one in 20 of a healthy individual's B cells is an ABC, the proportion gradually increases as we get older. The reasons for this increase are not yet fully understood, but may include previous infections. Certain people with weakened immune systems accumulate ABCs still faster. A team from the Medical Research Council (MRC) Toxicology Unit at the University of Cambridge, led by Dr James Thaventhiran, examined ABCs from two very different patient groups - one comprised of people with an inherited condition that impairs the activity of their immune systems and a second group comprised of cancer patients taking immunotherapy drugs - as well as from healthy individuals. Emily Horner, from Thaventhiran's lab, explained the aim of this research: "By looking at patients' B cells, we hoped to learn how we could stratify vulnerable patients - in other words, work out whether some patients were at greater risk from infection, even after vaccination, than others." The researchers measured the relative proportion of ABCs compared to healthy B cells, and used a technique known as single cell RNA sequencing to look in detail at the activity of cells. They also teamed up with Dr Nicholas Matheson, from the Cambridge Institute of Therapeutic Immunology and Infectious Disease, to test how these factors influenced the ability of a vaccinated individual's immune system to neutralise live SARS-CoV-2 virus. Dr Yam-Puc, also from the MRC Toxicology Unit, said: "What we found, much to our surprise, was that the age-associated B cells in these very different groups looked the same. The key difference was in the amount of these cells - the greater the proportion of ABCs in an individual's blood, the less effective that individual was post-vaccination at neutralising the virus." This could help explain the variability seen within particular patient groups in responses to the vaccine: people with fewer ABCs are likely to respond better to vaccines. Although the researchers examined ABCs in the context of responses to the SARS-CoV-2 vaccine, they believe that this phenomenon will almost certainly apply more widely, for example to the annual influenza vaccine. Dr Pehuen Pereyra Gerber, who performed the experiments with live SARS-CoV-2 virus in Matheson's lab, added: "Looking at blood levels of ABCs could tell us that person A should respond well to a vaccine, while person B might need a stronger vaccine or to be prioritised to receive a booster." Thaventhiran added: "Ultimately, this research could lead to the development of a clinical test to predict vaccine efficacy for immunodeficient patients, and for the population more generally." —ANI

Cambridge scientists have discovered a blood pattern that could help predict how well an individual will respond to immunisations

'Ageing' Immune Cell Levels May Predict How Well We Respond To Vaccines: Research

Florida: Scientists have discovered a unique method of strengthening honey bees' immune systems to help them fight lethal viruses, which have contributed to significant losses of the essential pollinator worldwide. The research team, which included entomologists from the University of Florida, the Agricultural Research Service-USDA, Louisiana State University, and the University of Nebraska-Lincoln, demonstrated in a new study that stimulating honey bee cells to produce free radicals helped the bees withstand a variety of viruses. In reality, in full-scale field trials, the treatment significantly decreased, and in some cases, completely eliminated, viral activity. "This approach is especially exciting because it doesn't just target a specific type of virus but helps with many different viruses," said Daniel Swale, senior author of the study. Swale is the associate director for training and special projects in the UF Emerging Pathogens Institute and associate professor in the UF/IFAS entomology and nematology department. "Additionally, we demonstrated that our treatment works both in the lab and in colonies that each contain 80,000 bees in the field. This is huge because, in a hive setting, bees are exposed to so many different viruses and stressors, so successfully controlling viruses in that environment is very encouraging," said Swale, who completed some of this research while at Louisiana State University. Honey bee colonies, and the beekeepers who manage them, play an important role in food production by pollinating many crops. In recent years, honey bee populations have seen significant declines, and viruses, while not the top cause of honey bee deaths, are among the main contributors. "Varroa mites are the number one cause of honey bee losses, but it's important to point out that varroa mites, aside from physically weakening bees, also transmit viruses to bees. If we can mitigate viruses in honey bee colonies, that would be a big step forward," said Michael Simone-Finstrom, a co-author of the study and a research molecular biologist with the ARS Honey Bee Breeding, Genetics, and Physiology Research Lab in Baton Rouge, Louisiana. In the experiment, the researchers used a compound called pinacidil to alter potassium ion channels, a protein found in the cells of bees' and most living things. Altering these channels produced slightly more free radicals. "While free radicals are often bad for cell health, in moderate amounts they can be therapeutic, as we see in this study. In this case, the additional free radicals signal to the immune system to ramp up, which helps the bees fight off viruses," said Troy Anderson, a co-author of the paper and a professor of entomology at the University of Nebraska-Lincoln. The scientists administered the drug to honey bee colonies by mixing it into sugar water and drizzling the water over the honey comb at night. The bees then consumed the sugar water and fed it to their young. During the day, bees are constantly moving in an out of the hive, so giving them the treatment at night maximizes the number of bees that will receive it. The treatment protected bees from six potentially deadly honey bee viruses: Israeli acute paralysis virus, deformed wing viruses A and B, black queen cell virus and Lake Sinai viruses 1 and 2. The researchers also showed that pinacidil helped more bees survive in colonies heavily infested with varroa mites. Administering pinacidil to commercial honey bee hives may only be feasible for some beekeepers, the researchers said, but the study opens the door to identifying other active ingredients that may work better and cost less. "One of the big take-aways from this study is that potassium ion channels can be a target for improving immune system function in honey bees and possibly other insects. We would like to find a molecule, such as a peptide, or a new technology that has the same effect as pinacidil but is more accessible to beekeepers," Swale said. —ANI

Scientists have discovered a unique method of strengthening honey bees' immune systems to help them fight lethal viruses

Immune-Boosting Therapy Helps Honey Bees Fight Viruses: Study

Washington: Researchers discovered that tropical mammals living within protected areas are not immune to the effects of human activity, even when it occurs outside the boundaries of the protected areas. The study, which was published in the journal Nature Ecology and Evolution, could aid 30 by 30 participants in making biodiversity policy decisions.  The study sheds light on how anthropogenic stressors like human population density and habitat fragmentation affect 159 mammal species across three biogeographic regions in 16 protected areas, based on the largest long-term camera-trap wildlife survey to date. As part of a collaboration between Conservation International, the Wildlife Conservation Society, and the Smithsonian Institution, a large-scale network of research stations agreed to implement a consistent data-collection protocol. It comprises millions of images collected over multiple years from over 1,000 camera-trap sites. "This data set is just phenomenal -- it was a herculean effort unlike anything attempted before," said Beaudrot, an assistant professor of biosciences. The study found that specialist species -- which occupy specific habitats only -- thrive when habitat fragmentation is low and are generally more susceptible to the negative impacts of human activities like hunting and land use than generalist species, which are able to live in more diverse habitats. Thus, a white-bellied pangolin living in the Bwindi Impenetrable National Park in Uganda should shuffle closer to its centre, since specialists are likely to fare better the farther inward they are from the edge of a protected area. "Habitats are more varied at the edge of the protected area," said Asuncion Semper-Pascual, a postdoctoral researcher at the Norwegian University for Life Sciences and the lead author of the study. "There is usually this difference between forest cover and open landscape, such as an area used for agriculture, etc. Some generalist species thrive in this diverse setting because it provides access to different resources." Generalist species, such as the tayra -- a dog-sized omnivore in the weasel family that is at home both under forest cover and in grasslands or cropland, only thrive near the edge of protected areas if human population density there is low. Understanding species-specific responses to different anthropogenic stressors can help set conservation priorities and guide protected-area management -- locally by focusing on the most vulnerable species in a region and globally by highlighting how landscape-scale factors impact biodiversity beyond the secure perimeter. "We have to think about the situation holistically," Beaudrot said. "Conservation is going to work best when it's tackled in specific contexts and in concert with the people who live there so as to create win-win situations for both the people and the wildlife." "As more protected areas are created, we need to think carefully about the factors both within and outside protected areas that influence biodiversity," Semper-Pascual said. (ANI) The study sheds light on how anthropogenic stressors like human population density and habitat fragmentation affect 159 mammal species across three biogeographic regions in 16 protected areas, based on the largest long-term camera-trap wildlife survey to date. As part of a collaboration between Conservation International, the Wildlife Conservation Society, and the Smithsonian Institution, a large-scale network of research stations agreed to implement a consistent data-collection protocol. It comprises millions of images collected over multiple years from over 1,000 camera-trap sites. "This data set is just phenomenal -- it was a herculean effort unlike anything attempted before," said Beaudrot, an assistant professor of biosciences. The study found that specialist species -- which occupy specific habitats only -- thrive when habitat fragmentation is low and are generally more susceptible to the negative impacts of human activities like hunting and land use than generalist species, which are able to live in more diverse habitats. Thus, a white-bellied pangolin living in the Bwindi Impenetrable National Park in Uganda should shuffle closer to its centre, since specialists are likely to fare better the farther inward they are from the edge of a protected area. "Habitats are more varied at the edge of the protected area," said Asuncion Semper-Pascual, a postdoctoral researcher at the Norwegian University for Life Sciences and the lead author of the study. "There is usually this difference between forest cover and open landscape, such as an area used for agriculture, etc. Some generalist species thrive in this diverse setting because it provides access to different resources." Generalist species, such as the tayra -- a dog-sized omnivore in the weasel family that is at home both under forest cover and in grasslands or cropland, only thrive near the edge of protected areas if human population density there is low. Understanding species-specific responses to different anthropogenic stressors can help set conservation priorities and guide protected-area management -- locally by focusing on the most vulnerable species in a region and globally by highlighting how landscape-scale factors impact biodiversity beyond the protected perimeter. "We have to think about the situation holistically," Beaudrot said. "Conservation is going to work best when it's tackled in specific contexts and in concert with the people who live there so as to create win-win situations for both the people and the wildlife." "As more protected areas are created, we need to think carefully about the factors both within and outside protected areas that influence biodiversity," Semper-Pascual said. —ANI

Researchers discovered that tropical mammals living within protected areas are not immune to the effects of human activity

Tropical Mammals Are Not Immune To Human Activity: Study

London: A team of Danish researchers have solved an old riddle about how Hepatitis C virus avoids the human body's immune defences. The result may have an impact on how we track and treat viral diseases in general. An estimated 50 million people worldwide are infected with chronic hepatitis C. The hepatitis C virus can cause inflammation and scarring of the liver, and in the worst case, liver cancer. Hepatitis C was discovered in 1989 and is one of the most studied viruses on the planet. Yet for decades, how it manages to evade the human immune system and spread through the body has been a riddle. Researchers at the University of Copenhagen and Hvidovre Hospital found that the virus just puts on a "mask", helping it to remain hidden while making copies of itself to infect new cells. The mask cloaks the virus in the form of a molecule already in our cells. Disguised by the molecule, our immune systems confuse the virus with something harmless that needn't be reacted to. "How the Hepatitis C virus manages to hide in our liver cells without being detected by the immune system has always been a bit of a mystery. Our revelation of the virus' masking strategy is important, as it could pave the way for new ways of treating viral infections. And it is likely that other types of viruses use the same trick," said Jeppe Vinther, Associate Professor of the university’s Department of Biology. The mask used by the hepatitis virus to hide in our cells is called FAD, a molecule composed of Vitamin B2 and the energy carrying molecule ATP. FAD is vital for our cells to convert energy. The FAD molecule's importance and familiarity to our cells makes it ideal camouflage for a malicious virus. For several years, the research team had a good idea that FAD was helping the virus hide in infected cells, but they lacked a clear way to prove it. To solve the challenge, they turned to Arabidopsis, a well-known experimental plant among researchers. "We were getting desperate to find a way to prove our hypothesis, which is when we purified an enzyme from the Arabidopsis plant that can split the FAD molecule in two," explained Anna Sherwood from the Department of Biology. Using the enzyme, the researchers were able to split the FAD and prove that the hepatitis C virus used it as a mask. —IANS

A team of Danish researchers have solved an old riddle about how Hepatitis C virus avoids the human body's immune defences

Scientists Find How Hepatitis C Virus Avoids Immune System

Washington: Researchers from the National Institutes of Health (NIH) discovered in a recent study that infants with mitochondrial abnormalities had altered B cell function, which resulted in a weaker and less varied antibody response to viral infections. Researchers at the National Human Genome Research Institute (NHGRI) led the study, which was published in Frontiers in Immunology. They examined the gene activity of immune cells in kids with mitochondrial disorders and discovered that B cells, which make antibodies to fight viral infections, are less able to withstand cellular stress. "Our work is one of the first examples to study how B cells are affected in mitochondrial disease by looking at human patients," said Eliza Gordon-Lipkin, M.D., assistant research physician in NHGRI's Metabolism, Infection and Immunity Section and co-first author of the paper. Due to their role in converting oxygen and food into energy, mitochondria are essential parts of almost every cell in the body. Depending on which cells are impacted, mitochondrial diseases associated to genomic variations in more than 350 genes present a range of symptoms. "For children with mitochondrial disorders, infections can be life threatening or they can worsen the progression of their disorder," said Peter McGuire, M.B.B.Ch., NHGRI investigator, head of the Metabolism, Infection and Immunity Section and senior author of the study. "We wanted to understand how immune cells differ in these patients and how that influences their response to infections." Around 1 in 5,000 people worldwide have a mitochondrial disorder. Examples of mitochondrial disorders are Leigh's syndrome, which primarily affects the nervous system, and Kearns-Sayre syndrome, which primarily affects the eyes and heart. While mitochondrial disorders are known to affect organs such as the heart, liver, and brain, less is known how they affect the immune system. Using a genomic technique called single-cell RNA sequencing, which analyzes gene activity in different cell types, researchers studied immune cells found in blood. These cells include different types of white blood cells that help the body fight infections. During stressful conditions, these cells produce a microRNA called mir4485. MicroRNAs are small strings of RNA that help control when and where genes are turned on and off. mir4485 controls cellular pathways that help cells survive. "We think that B cells in these patients undergo cellular stress when they turn into plasma cells and produce antibodies, and these B cells then try to survive by producing the microRNA to cope," said Dr. McGuire. "But the B cells are too fragile due to their limited energy, so they are unable to survive the stressful conditions." Researchers used a technique called VirScan to look at all past viral infections, assess how well the immune system fought those infections and see the effects of B cells and plasma cells on antibody production. With a weaker antibody response, the immune systems in children with mitochondrial disorders are less able to recognize and neutralize invading viruses and clear infections. Researchers aim to use the results of this study to guide future treatment of patients with mitochondrial disorders, noting that more translational studies are needed in this research area. —ANI

Researchers from the National Institutes of Health (NIH) discovered in a recent study that infants with mitochondrial

Study Finds How Weaker Immune Response To Viral Infections In Children With Mitochondrial Disorders

New York: Severe Covid-19 may cause long-lasting alterations to the innate immune system, the first line of defence against pathogens, according to a small study. These changes may help explain why the disease can damage so many different organs and why some people with long Covid have high levels of inflammation throughout the body. The study, published online in the journal Cell, examined immune cells and molecules in blood samples from 38 people recovering from severe Covid and other severe illnesses, as well as from 19 healthy people. Notably, researchers led by Steven Z. Josefowicz, from the Weill Cornell Medicine in New York City in the US, established a new technique for collecting, concentrating and characterising very rare blood-forming stem cells that circulate in the blood, eliminating the need to extract such cells from bone marrow. In these rare stem cells -- the parents of immune-system cells -- taken from people recovering from Covid, the scientists identified changes in the instructions for which genes got turned on or off. These changes were passed down to daughter cells, leading them to boost production of immune cells called monocytes. In the monocytes from people recovering from severe Covid, the changes in gene expression led the cells to pump out greater amounts of molecules called inflammatory cytokines than monocytes from people who were healthy or had non-Covid illnesses. The researchers observed these changes as much as a year after the participants came down with Covid. Due to the small number of study participants, the scientists could not establish a direct association between the cellular and molecular changes and health outcomes. The investigators suspected that an inflammatory cytokine called IL-6 might play a role in establishing the changes in gene-expression instructions. They tested their hypothesis both in mice with Covid-like disease and in people with Covid. In these experiments, some of the subjects received antibodies at the early stage of illness that prevented IL-6 from binding to cells. During recovery, these mice and people had lower levels of altered stem cell gene-expression instructions, monocyte production and inflammatory cytokine production than subjects that didn't receive the antibody. In addition, the lungs and brains of mice that received the antibodies had fewer monocyte-derived cells and less organ damage. These findings suggest that SARS-CoV-2 can cause changes in gene expression that ultimately boost the production of inflammatory cytokines, and one type of those cytokines perpetuates the process by inducing these changes in stem cells even after the illness is over. In addition, the findings suggest that early-acting IL-6 is likely a major driver of long-term inflammation in people with severe Covid. These findings shed light on the pathogenesis of SARS-CoV-2 infection and may provide new leads for therapies. The results also underscore the importance of staying up to date with recommended Covid vaccines, which are proven to protect against serious illness, hospitalisation and death. —IANS

Severe Covid-19 may cause long-lasting alterations to the innate immune system

 Severe Covid May Cause Long-Term Innate Immune System Changes: Study

London: While humankind aims for manned missions to the Moon and Mars, a new study showed that T-cells of the immune system can get affected by weightlessness in space and render them ineffective to fight infections. Space is an extremely hostile environment that poses threats to human health. One such threat is changes to the immune system that occur in astronauts while in space and that persist after their return to Earth, said researchers in the study, published in the journal Science Advances. This immune deficiency can leave them more vulnerable to infection and lead to the reactivation of latent viruses in the body. "If astronauts are to be able to undergo safe space missions, we need to understand how their immune systems are affected and try to find ways to counter harmful changes to it," said Lisa Westerberg, principal researcher at the Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet in Sweden. "We've now been able to investigate what happens to T-cells, which are a key component of the immune system, when exposed to weightless conditions," Westerberg added. In the study, the researchers have tried to simulate weightlessness in space using a method called dry immersion. This involves a custom-made waterbed that tricks the body into thinking it is in a weightless state. The researchers examined T-cells in the blood of eight healthy individuals for three weeks of exposure to simulated weightlessness. Blood analyses were performed before the experiment started, at seven, 14 and 21 days after the start, and at seven days after the experiment ended. They found that the T-cells significantly changed their gene expression -- that is to say, which genes were active and which were not -- after seven and 14 days of weightlessness and that the cells became more immature in their genetic program. The greatest effect was seen after 14 days. "The T cells began to resemble more so-called naive T-cells, which have not yet encountered any intruders. This could mean that they take longer to be activated and thus become less effective at fighting tumour cells and infections. Our results can pave the way for new treatments that reverse these changes to the immune cells' genetic programme," said Carlos Gallardo Dodd, doctoral student at the Institutet’s Department of Microbiology, Tumour and Cell Biology. After 21 days, the T-cells had "adapted" their gene expression to weightlessness so that it had almost returned to normal, but analyses carried out seven days after the experiment ended showed that the cells had regained some of the changes. —IANS

While humankind aims for manned missions to the Moon and Mars, a new study showed that T-cells

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Durability And Effectiveness Of Immune Response Against COVID-19: Study

Inam Ansari

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Durability And Effectiveness Of Immune Response Against COVID-19: Study

Inam Ansari

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