Publisher Health

Even the mention of parasites can be enough to make some people’s skin crawl. But to recent UC Santa Barbara doctoral graduate Dana Morton these creepy critters occupy important ecological niches, fulfilling roles that, in her opinion, have too often been overlooked.
That’s why Morton has just released the most extensive ecological food web that includes parasites. Eight years in the making, the dataset includes over 21,000 interactions between 942 species, all thoroughly annotated. The detailed description, published in the journal Scientific Data, is a boon for basic research, conservation efforts and resource management.
Understanding who eats whom, or trophic interactions, in an ecosystem is prime information for biologists. These relationships alone can tell researchers a great deal about a system, its complexity and even its overall health. However, ecologists often overlook parasites when investigating these interactions, perhaps because parasitology only recently joined the sphere of ecology, emerging from the medical sciences.
“But you can’t overlook parasite interactions once you know about them,” said Morton. “If you’re ignoring half of the interactions in the system, you don’t really know what’s going on in that system.”
Previous work led by her mentors, Armand Kuris and Kevin Lafferty in the Department of Ecology, Evolution, and Marine Biology, found that parasites were common in estuarine food webs. But Morton wanted to tackle a more diverse ecosystem. Given the body of research conducted on California’s kelp forests, she thought it would be easy enough to simply add parasites and small, free-living invertebrates to an existing network. But she quickly realized that previous food webs compiled for the kelp forest were too coarse to build on. They focused on big fish eating little fish, but gave less attention to mammals, birds and invertebrates. She’d need to start from scratch.
An exhaustive endeavor
First Morton compiled a list of species that call the kelp forest home. She and her co-authors used basically every credible source they could find. They pored over literature reviews and got data from long-term research projects, like the Santa Barbara Coastal Long Term Ecological Research Program and the Channel Islands National Park Kelp Forest Monitoring program. She also sought out fellow divers, and when that wasn’t enough, Morton and her team conducted their own field sampling.

Being constantly hungry, no matter how much you eat — that’s the daily struggle of people with genetic defects in the brain’s appetite controls, and it often ends in severe obesity. In a study published in Science on April 15, researchers at the Weizmann Institute of Science, together with colleagues from the Queen Mary University of London and the Hebrew University of Jerusalem, have revealed the mechanism of action of the master switch for hunger in the brain: the melanocortin receptor 4, or MC4 receptor for short. They have also clarified how this switch is activated by setmelanotide (Imcivree), a drug recently approved for the treatment of severe obesity caused by certain genetic changes. These findings shed new light on the way hunger is regulated and may help develop improved anti-obesity medications.
The MC4 receptor is present in a brain region called the hypothalamus — within a cluster of neurons that compute the body’s energy balance by processing a variety of energy-related metabolic signals. When the MC4 is activated, or “on” — as it normally is — it sends out commands that cause us to feel full, which means that from the brain’s perspective, our default state is satiety. When our energy levels drop, the hypothalamic cluster produces a “time to eat” hormone that inactivates, or turns off the MC4 receptor, sending out a “become hungry” signal. After we eat, a second, “I’m full” hormone is released. It binds to the same active site on the MC4, replacing the hunger hormone and turning the receptor back on — bringing us back to the satiety default. Mutations that inactivate the MC4 cause people to feel constantly hungry.
MC4 is a prime target for anti-obesity drugs, such as setmelanotide, precisely because it’s a master switch: turning it on can control hunger while bypassing all other energy-related signals. But until now it was unknown how exactly this hunger switch works.
The new study began with the predicament of one family, in which at least eight members, plagued by persistent hunger, were severely obese — most of them with a body mass index of over 70, that is, about triple the norm. Their medical history came to the attention of Hadar Israeli, a medical student pursuing PhD studies into the mechanisms of obesity under the guidance of Dr. Danny Ben-Zvi at the Hebrew University of Jerusalem. Israeli was struck by the fact that the family’s plight was due to a single mutation that ran in the family: one affecting the MC4 receptor. She turned to Dr. Moran Shalev-Benami of Weizmann’s Chemical and Structural Biology Department, asking whether new advances in electron microscopy could help explain how this particular mutation could produce such a devastating effect.
Shalev-Benami decided to launch a study into the structure of MC4, inviting Israeli to join her lab as a visiting scientist. Together with Dr. Oksana Degtjarik, a postdoctoral fellow in the lab, Israeli isolated large quantities of pure MC4 receptor from cell membranes, let it bind with setmelanotide and determined its 3D structure using cryogenic electron microscopy. The study was conducted in collaboration with the teams of Dr. Peter J. McCormick from the Queen Mary University of London and of Prof. Masha Y. Niv from the Hebrew University of Jerusalem.
The 3D structure revealed that setmelanotide activates the MC4 receptor by entering its binding pocket — that is, by directly hitting the molecular switch that signals satiety, even more potently than the natural satiety hormone. It also turned out that the drug has a surprising helper: an ion of calcium that enters the pocket, enhancing the drug’s binding to the receptor. In biochemical and computational experiments, the scientists found that similarly to the drug, calcium also assists the natural satiety hormone.

People who have recovered from COVID-19 had a robust antibody response after the first mRNA vaccine dose, but little immune benefit after the second dose, according to new research from the Penn Institute of Immunology. The findings, published today in Science Immunology, suggest only a single vaccine dose may be needed to produce a sufficient antibody response. The team found that those who did not have COVID-19 — called COVID naïve — did not have a full immune response until after receiving their second vaccine dose, reinforcing the importance of completing the two recommended doses for achieving strong levels of immunity.
The study provides more insight on the underlying immunobiology of mRNA vaccines, which could help shape future vaccine strategies.
“These results are encouraging for both short- and long-term vaccine efficacy, and this adds to our understanding of the mRNA vaccine immune response through the analysis of memory B cells,” said senior author E. John Wherry, PhD, chair of the department of Systems Pharmacology and Translational Therapeutics and director of the Penn Institute of Immunology in the Perelman School of Medicine at the University of Pennsylvania.
The human immune response to vaccines and infections result in two major outcomes — the production of antibodies that provide rapid immunity and the creation of memory B cells, which assist in long-term immunity. This study represents one of the first to uncover how memory B cell responses differ after vaccination in people who previously experienced infection, compared to those who have not have COVID-19.
“Previous COVID-19 mRNA vaccine studies on vaccinated individuals have focused on antibodies more than memory B cells. Memory B cells are a strong predictor of future antibody responses, which is why it’s vital to measure B cell responses to these vaccines,” Wherry said. “This effort to examine memory B cells is important for understanding long-term protection and the ability to respond to variants.”
The researchers recruited 44 healthy individuals who received either the BioNTech/Pfizer or Moderna mRNA COVID-19 vaccine at the University of Pennsylvania Health System. Of this cohort, 11 had a prior COVID-19 infection. Blood samples were collected for deep immune analyses four times prior to and after vaccine doses.

The list of known genetic mitochondrial disorders is ever-growing, and ongoing research continues to identify new disorders in this category. In an article recently published in Brain, a Japanese-European team of scientists, including researchers from Fujita Health University, describe mutations in the LIG3 gene, which plays a crucial role in mitochondrial DNA replication. These mutations cause a previously unknown syndrome characterized by gut dysmotility, leukoencephalopathy, and neuromuscular abnormalities.
DNA ligase proteins, which facilitate the formation of bonds between separate strands of DNA, play critical roles in the replication and maintenance of DNA. The human genome encodes three different DNA ligase proteins, but only one of those proteins — DNA ligase III (LIG3) — is expressed in mitochondria. LIG3 is therefore crucial for mitochondrial health, and inactivation of the homologous protein in mice causes profound mitochondrial dysfunction and early embryonic mortality. In an article recently published in the peer-reviewed journal Brain, a team of European and Japanese scientists, led by Dr. Mariko Taniguchi-Ikeda from Fujita Health University Hospital, describes a set of seven patients with a novel mitochondrial disorder caused by biallelic variants in the gene that encodes the LIG3 protein, called the “LIG3” gene. Their report provides a description of the patients’ symptoms and a mechanistic exploration of the mutations’ effects.
For Dr. Taniguchi-Ikeda, the investigation began with her desire to help a young patient. “I wanted to make a distinct clinical and genetic diagnosis for the affected patient,” she explains, “because his elder brother had passed away and the surviving boy was referred to my outpatient ward for detailed genetic tests.” By performing whole-exome sequencing of DNA from the surviving patient, Dr. Taniguchi-Ikeda discovered that he had inherited a p.P609L LIG3 variant from his father and a p.R811Ter LIG3 variant from his mother. The parents had kept the deceased brother’s dried umbilical cord, and by analyzing DNA extracted from that source, Dr. Taniguchi-Ikeda confirmed that the brother had carried the same LIG3 variants.
Having detected a novel genetic mitochondrial disorder, Dr. Taniguchi-Ikeda wished to conduct further research by identifying other patients with pathogenic LIG3 variants. She could find no other such cases in Japan, but through a collaboration with Dr. Makiko Tsutsumi from Fujita Health University and researchers in Europe, including Professor Elena Bonora from the University of Bologna and Professor Roberto De Giorgio from the University of Ferrara, she learned of two European families also affected by such variants. One was an Italian family in which three brothers had all inherited a p.K537N variant from their father and a p.G964R variant from their mother, and the other was a Dutch family in which two daughters had inherited a p.R267Ter variant from their father and a p.C999Y variant from their mother.
These patients experienced a complex syndrome involving severe gut dysmotility and neurologic abnormalities as the most consistently observed clinical signs. The neurologic abnormalities included leukoencephalopathy, epilepsy, migraine, stroke-like episodes, and neurogenic bladder. The prominent changes in the gut were decreased myenteric neuron counts and elevated fibrosis and elastin levels. Muscle pathology assessments revealed decreased staining intensities for cytochrome C oxidase.
To better characterize how the patients’ LIG3 mutations could lead to such phenotypes, the researchers conducted experiments both in vitro and on zebrafish. The in vitro experiments with patient-derived fibroblasts showed that the mutations resulted in reduced LIG3 protein levels and diminished ligase activity. The consequent deficits in mitochondrial DNA maintenance would do much to explain the patients’ presentations. Experiments with zebrafish showed that disrupting the lig3 gene produced brain alterations and gut transit impairments analogous to those observed in the patients.
The study brings to light a novel disorder resulting from disruption of a gene that plays a critical role in the maintenance of mitochondrial DNA. In describing the importance of these findings, Dr. Taniguchi-Ikeda concludes, “Our study may facilitate efforts to diagnose patients with mitochondrial diseases. Our findings will also be beneficial to future investigations into the mitochondrial DNA repair system.”
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SharecloseShare pageCopy linkAbout sharingimage copyrightGetty ImagesThe risk of developing a serious brain clot – known as a cerebral venous sinus thrombosis (CVST) – is 8 to 10 times higher in people with Covid than those who get a vaccine, a study suggests.Based on US data, the Oxford research team says people being vaccinated should be reassured by the findings.It follows investigations into links between the AstraZeneca vaccine and rare blood clots.The study only looked at those who had had a Pfizer or Moderna vaccine.The research, which involved electronic health records of 81 million people in the US, looked at the number of CVST cases seen in the two weeks following a diagnosis of coronavirus and the number of cases occurring in the two weeks after people had their first coronavirus vaccine.It estimates that while these blood clots are uncommon after Covid – with 39 in every million people developing one within two weeks of being ill – they are much rarer still after a vaccine.’Work in progress’But researchers say their study – which has not been through a formal review and is separate from the Oxford vaccine group – is still a work in progress and must be interpreted cautiously because it is difficult to calculate with certainty how common CVSTs are in the general population, partly because of just how rare they are. The study also found:Clots were more common in people who already had cardiovascular disease80% of people who have the clots surviveSome cases were seen in under-30s, showing they are not immune to serious complications from coronavirusIn those who had an mRNA vaccine – such as the Pfizer or Moderna jab – they estimate CVSTs occurred in around four in a million people. Scientists say their study cannot identify whether vaccines are linked to these clots and much larger studies are needed to address this. They say a more complete database would be needed because as in cases it was unclear exactly which mRNA vaccine had been given There are no directly comparable figures for the AZ vaccine because this jab has not been used in the USThe European Medicines Agency says a particular type of CVST occurs in around five in a million people after the first dose of the Oxford-AstraZeneca vaccine – but the populations vaccinated were not the same as in the US and the rates cannot be compared.Paul Harrison, professor of psychiatry at the University of Oxford, said their study had important conclusions for people deciding on vaccines.He said: “Firstly, Covid-19 markedly increases the risk of CVST, adding to the list of blood clotting problems this infection causes. “Secondly, the Covid-19 risk is higher than seen with the current vaccines, even for those under 30; something that should be taken into account when considering the balances between risks and benefits for vaccination.”Rare blood clots – what you need to knowWhere is there surge testing for Covid variants?Is the Oxford-AstraZeneca vaccine safe?From their database they were unable to investigate whether the CVST clots they were seeing had similar features to those seen in rare cases after vaccines – which all had a peculiar pattern of blood cells associated with them, where certain cells called platelets were diminished.Prof Beverley Hunt, of Thrombosis UK, said the mechanisms behind people getting clots after Covid and those experiencing clots after vaccines were likely to be different. She said: “Patients who are hospitalised with Covid-19 have very pro-thrombotic (sticky) changes in their blood, which persist after they have been discharged. This will lead to an increased rate of blood clots. “The mechanism for the very rare blood clots and low platelet counts seen after the AstraZeneca vaccine is different. It is associated with an immune response.”Related Internet LinksOSF COVID-CVT-paper.pdf.websiteThe BBC is not responsible for the content of external sites.

One consequence of the coronavirus pandemic has been global restrictions on mobility. This, in turn, has had an effect on pollution levels in the atmosphere. Researchers from across the world are using this unique opportunity to take measurements, collect data, and publish studies. An international team led by Forschungszentrum Jülich’s Institute of Climate and Energy Research — Troposphere has now published a comprehensive review providing an overview of results up to September 2020. The study also has its own dedicated website, where additional measurement data can be added to supplement and refine existing research results. At the same time, this collection of data allows scientifically substantiated predictions to be made about the pollution levels of future mobility scenarios.
The meta-analysis was coordinated by Prof. Astrid Kiendler-Scharr, director at Jülich’s Institute of Climate and Energy Research — Troposphere. The analysis covers the measurement data of around 200 studies from the first seven months following the onset of the pandemic. It focuses on the following air pollutants: nitrogen dioxide, particulate matter, ozone, ammonia, sulfur dioxide, black carbon, volatile organic compounds (VOCs), and carbon monoxide. A third of the studies take into account the prevailing meteorological situation when calculating the influence of lockdowns on the air composition. The Government Stringency Index (SI) — summarizing the severity of local shutdown measures in a number that can be compared at international level — acted as a reference value.
A key finding of the analysis is that lockdowns, which have the sole aim of slowing down the infection rate, are also reducing the global pollution of the atmosphere with nitrogen dioxide and particulate matter — the higher the SI, the greater this impact. However, this only applies to pollutants that primarily have an anthropogenic origin, i.e. are directly emitted by humans, especially in the field of mobility. In contrast, ozone levels increased. This increase was a result of atmospheric chemical processes caused by reduced nitrogen oxide levels in the air.
The study also highlights current gaps in the data collection and the need for further research. The authors are therefore of the opinion that the period of analysis should be extended to cover the entire year of 2020. The scientists place a particular emphasis on hydrocarbons, which have so far only been examined sporadically in studies, and on extended analyses looking at the impact of emission changes on the climate.
An important addition to the meta-analysis is a database that can be accessed via a website (COVID-19 Air Quality Data Collection — https://covid-aqs.fz-juelich.de/). It contains all data from the study on pollution levels, including data on pollutions levels in individual countries. Researchers can also find a list of publications to date and thus obtain a quick overview of previous studies.
The website also invites scientists to present data from their new studies and to thus become part of the reference system. It therefore acts as a “living version,” with the presentation of collected results being constantly refined. Similarly, there are plans to further develop the data collection to include measurement results and the analysis of other pollutants that are not part of the current canon, for example hydrocarbons.
The important data could also form the basis for better assessments of the impacts on atmospheric chemistry in future scenarios. This includes a considerable, long-term reduction in pollution levels for a comprehensive transition to electromobility.
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One of the characteristic hallmarks of Alzheimer’s disease (AD) is the buildup of amyloid-beta plaques in the brain. Most therapies designed to treat AD target these plaques, but they’ve largely failed in clinical trials. New research by Salk scientists upends conventional views of the origin of one prevalent type of plaque, indicating a reason why treatments have been unsuccessful.
The traditional view holds that the brain’s trash-clearing immune cells, called microglia, inhibit the growth of plaques by “eating” them. The Salk scientists show instead that microglia promote the formation of dense-core plaques, and that this action sweeps wispy plaque material away from neurons, where it causes cell death. The research, which was published in Nature Immunology on April 15, 2021, suggests that dense-core plaques play a protective role, so treatments to destroy them may do more harm than good.
“We show that dense-core plaques don’t form spontaneously. We believe they’re built by microglia as a defense mechanism, so they may be best left alone,” says Greg Lemke, a professor in Salk’s Molecular Neurobiology Laboratory. “There are various efforts to get the FDA to approve antibodies whose main clinical effect is reducing dense-core plaque formation, but we make the argument that breaking up the plaque may be doing more damage.”
Alzheimer’s disease is a neurological condition that results in memory loss, impairment of thinking, and behavioral changes, which worsen as we age. The disease seems to be caused by abnormal proteins aggregating between brain cells to form the hallmark plaques, which interrupt activity that keeps the cells alive.
There are numerous forms of plaque, but the two most prevalent are characterized as “diffuse” and “dense-core.” Diffuse plaques are loosely organized, amorphous clouds. Dense-core plaques have a compact center surrounded by a halo. Scientists have generally believed that both types of plaque form spontaneously from excess production of a precursor molecule called amyloid precursor protein (APP).
But, according to the new study, it is actually microglia that form dense-core plaques from diffuse amyloid-beta fibrils, as part of their cellular cleanup.

A new study shows that markers of fear recall differ between men and women, but in a hormone-dependent manner.
Aberrant fear-memory processing in the brain is thought to underlie anxiety disorders, which affect hundreds of millions of people worldwide. The neurobiological mechanisms underlying these disorders remain poorly understood, but recent studies suggest that neural oscillations in the prefrontal cortex can reflect the strength of fear recall activity, providing a physiological measure.
Women suffer from anxiety disorders at twice the rate of men and indeed the literature shows that there are sex differences in fear recall behaviors, but this area of study has not been extended to neural oscillations. Additional studies suggest a modulatory role for the female sex hormone estradiol (E2) for fear recall and extinction recall.
The new study led by Ursula Stockhorst, PhD, at the University of Osnabrück, Germany, specifically shows that peripheral and brain markers of fear recall differ in a hormone-dependent manner between men and women.
The work appears in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier.
Cameron Carter, MD, Editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, said of the work: “This study sheds light on the well-known differences between men and women in their vulnerability to anxiety disorders and shows that aspects of fear learning and extinction that contribute to vulnerability in women are related to differences in estrogen levels.”
For the study, first author and PhD student Philipp Bierwirth, MSc, and colleagues examined 20 men, 20 women using oral hormonal contraceptives (OC) and 20 free-cycling women during their mid-cycle (MC). Women taking OC have suppressed and thus low endogenous E2 levels, whereas free-cycling MC women have higher levels of E2.
Participants underwent a fear-conditioning paradigm in which two of four photographs of neutral male faces were paired with a loud burst of white noise. Following the conditioning, the subjects underwent fear extinction, in which two photographs — only one of which had been paired with the noise — were again presented, but this time with no noise stimulus. The next day, subjects were shown all four photographs again, including the two that had been presented in the extinction phase and thus ready for extinction recall, and two of them without previous extinction — thus subject to fear recall. During all presentations, the researchers measured skin conductance responses (SCR), a peripheral readout of fear expression, and brain oscillations measured by electroencephalography.
Mr. Bierwirth said: “We found stronger peripheral fear expression (via SCR) during fear recall and extinction recall under low-E2 conditions, that is, in men and in OC women, compared to mid-cycle women with higher E2 levels. Most importantly, we also observed enhanced theta oscillations in the medial prefrontal cortex and especially in the dorsal anterior cingulate cortex (dACC), in men and OC women compared to MC women.”
Importantly, the authors also point out that subjects were examined during their natural E2 status. They were not randomized to experimentally manipulated estrogen levels and so causal inferences about estrogen cannot be drawn.
Fear recall-related dACC theta oscillations were attenuated in women with higher E2 levels, which, importantly, supports previous findings suggesting a protective role for E2 against fear overexpression during the recall of fear and extinction memories. The data demonstrate that peripheral and brain oscillatory correlates of fear memory recall do not differ between the sexes per se but vary with E2 status, even among women.
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Patients who are overweight or obese have more severe COVID-19 and are highly likely to require invasive respiratory support, according to a new international study.
The research, led by the Murdoch Children’s Research Institute (MCRI) and The University of Queensland and published in Diabetes Care, found obese or overweight patients are at high risk for having worse COVID-19 outcomes. They are also more likely to require oxygen and invasive mechanical ventilation compared to those with a healthy weight.
MCRI researcher Dr Danielle Longmore said the findings, which highlighted the relationship between obesity and increased COVID-19 disease burden, showed the need to urgently introduce strategies to address the complex socio-economic drivers of obesity, and public policy measures such as restrictions on junk food advertising.
“Although taking steps to address obesity in the short-term is unlikely to have an immediate impact in the COVID-19 pandemic, it will likely reduce the disease burden in future viral pandemics and reduce risks of complications like heart disease and stroke,” she said.
The study looked at hospitalised SARS-CoV-2 patients from 18 hospitals in 11 countries including China, America, Italy, South Africa and The Netherlands.
Among the 7244 patients aged 18 years and over, 34.8 per cent were overweight and 30.8 per cent were obese.