Culture

Scientists at the Center for Infection and Immunity (CII) at Columbia University Mailman School of Public Health and SunYat-Sen University in China have set the stage for the development of highly sensitive antibody tests for infection with all known human coronaviruses, including new variants of SARS-CoV-2. These tests should also allow differentiation of immune responses due to infection and vaccination. The research is published in Communications Biology, a Nature journal.

The HCoV-Peptide array developed by CII scientists consists of 3 million immune markers on a glass chip, covering proteins of all known human coronaviruses, including the SARS-CoV-2. In collaboration with a team at Sun Yat-Sen University, the CII researchers identified 29 immune signatures specific to SARS-CoV-2. These genetic fingerprints (peptides) provide the blueprint for tests that will be used for diagnostics and surveillance. Current antibody tests for SARS-CoV-2 infection may generate false positive results because of cross-reactivity with seasonal coronaviruses responsible for the common cold, as well as MERS-CoV and SARS-CoV-1.

To develop the HCoV-Peptide array, the researchers first analyzed blood samples taken from individuals with asymptomatic, mild, or severe SARS-CoV-2 infections, and controls including healthy individuals and those exposed to SARS-CoV-1 and seasonal coronaviruses. An analysis of all ~170,000 peptides related to known human coronaviruses yielded 29 peptides with the strongest and most specific reactivity with SARS-CoV-2. Next, they validated their test using a second set of blood samples, including those from confirmed cases of SARS-CoV-2, those with antibodies to other human coronaviruses, and healthy individuals.

The new test has a 98 percent specificity and sensitivity. Immune signatures were present from eight days after onset of COVID-19 symptoms to as long as six to seven months after infection.

"This work will allow us and others to build inexpensive, easy to use blood tests that can provide data for exposure as well as immunity," says author Nischay Mishra, PhD, assistant professor of epidemiology at the Columbia Mailman School.

"This work with our colleagues at SunYat-Sen, led by Professor Jiahai Lu, and with Nimble Therapeutics, underscores the importance to public health of global collaboration and partnerships with industry in addressing the challenges of the COVID-19 pandemic," says senior and corresponding author W. Ian Lipkin, MD, director of CII.

Previously, the researchers have used similar methods to develop tests for Zika, acute flaccid myelitis, and tick-borne infections.

New research has found that a group of genes that reduces the risk of developing severe COVID-19 by around 20% is inherited from Neanderthals

These genes, located on chromosome 12, code for enzymes that play a vital role in helping cells destroy the genomes of invading viruses

The study suggests that enzymes produced by the Neanderthal variant of these genes are more efficient which helps protect against severe COVID-19

This genetic variant was passed to humans around 60,000 years ago via interbreeding between modern humans and Neanderthals

The genetic variant has increased in frequency over the last millennium and is now found in around half of people living outside Africa

SARS-CoV-2, the virus that causes COVID-19, impacts people in different ways after infection. Some experience only mild or no symptoms at all while others become sick enough to require hospitalization and may develop respiratory failure and die.

Now, researchers at the Okinawa Institute of Science and Technology Graduate University (OIST) in Japan and the Max Planck Institute for Evolutionary Biology in Germany have found that a group of genes that reduces the risk of a person becoming seriously ill with COVID-19 by around 20% is inherited from Neanderthals.

"Of course, other factors such as advanced age or underlying conditions such as diabetes have a significant impact on how ill an infected individual may become," said Professor Svante Pääbo, who leads the Human Evolutionary Genomics Unit at OIST. "But genetic factors also play an important role and some of these have been contributed to present-day people by Neanderthals."

Last year, Professor Svante Pääbo and his colleague Professor Hugo Zeberg reported in Nature that the greatest genetic risk factor so far identified, doubling the risk to develop severe COVID-19 when infected by the virus, had been inherited from Neanderthals.

Their latest research builds on a new study, published in December last year from the Genetics of Mortality in Critical Care (GenOMICC) consortium in the UK, which collected genome sequences of 2,244 people who developed severe COVID-19. This UK study pinpointed additional genetic regions on four chromosomes that impact how individuals respond to the virus.

Now, in a study published today in PNAS, Professor Pääbo and Professor Zeberg show that one of the newly identified regions carries a variant that is almost identical to those found in three Neanderthals - a ~50,000-year-old Neanderthal from Croatia, and two Neanderthals, one around 70,000 years old and the other around 120,000 years old, from Southern Siberia.

Surprisingly, this second genetic factor influences COVID-19 outcomes in the opposite direction to the first genetic factor, providing protection rather than increasing the risk to develop severe COVID-19. The variant is located on chromosome 12 and reduces the risk that an individual will require intensive care after infection by about 22%.

"It's quite amazing that despite Neanderthals becoming extinct around 40,000 years ago, their immune system still influences us in both positive and negative ways today," said Professor Pääbo.

To try to understand how this variant affects COVID-19 outcomes, the research team took a closer look at the genes located in this region. They found that three genes in this region, called OAS, code for enzymes that are produced upon viral infection and in turn activate other enzymes that degrade viral genomes in infected cells.

"It seems that the enzymes encoded by the Neanderthal variant are more efficient, reducing the chance of severe consequences to SARS-CoV-2 infections," Professor Pääbo explained.

The researchers also studied how the newly discovered Neanderthal-like genetic variants changed in frequency after ending up in modern humans some 60,000 years ago.

To do this, they used genomic information retrieved by different research groups from thousands of human skeletons of varying ages.

They found that the variant increased in frequency after the last Ice Age and then increased in frequency again during the past millennium. As a result, today it occurs in about half of people living outside Africa and in around 30% of people in Japan. In contrast, the researchers previously found that the major risk variant inherited from Neanderthals is almost absent in Japan.

"The rise in the frequency of this protective Neanderthal variant suggests that it may have been beneficial also in the past, maybe during other disease outbreaks caused by RNA viruses," said Professor Pääbo.

Last year, researchers at Karolinska Institutet in Sweden and the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany showed that a major genetic risk factor for severe COVID-19 is inherited from Neandertals. Now the same researchers show, in a study published in PNAS, that Neandertals also contributed a protective variant. Half of all people outside Africa carry a Neandertal gene variant that reduces the risk of needing intensive care for COVID-19 by 20 percent.

Some people become seriously ill when infected with SARS-CoV-2 while others get only mild or no symptoms. In addition to risk factors such as advanced age and diabetes, gene variants also make people more or less sensitive to developing severe COVID-19. A major genetic risk factor is located on chromosome 3 and dramatically increases the risk of respiratory failure and even death. Hugo Zeberg and Svante Pääbo at Karolinska Institutet and the Max Planck Institute for Evolutionary Anthropology discovered last year that this risk variant is inherited from Neandertals.

Now the research duo shows that the Neandertals also contributed a protective variant to present-day people. They find that a region on chromosome 12 that reduces the risk of needing intensive care upon infection with the virus by 20 percent is inherited from Neandertals. The genes in this region are called OAS and regulate the activity of an enzyme that breaks down viral genomes, and the Neandertal variant of the enzyme seems to do this more efficiently.

"This shows that our heritage from Neandertals is a double-edged sword when it comes to our response to SARS-CoV-2. They have given us variants that we can both curse and thank them for," says Hugo Zeberg, researcher at the Department of Neuroscience, Karolinska Institutet, and the Max Planck Institute for Evolutionary Anthropology.

The study also shows that the protective variant from Neandertals has increased in frequency since the last Ice Age so that it is now carried by about half of all people outside Africa.

"It is striking that this Neandertal gene variant has become so common in many parts of the world. This suggests that it has been favourable in the past," says Svante Pääbo, director at the Max Planck Institute for Evolutionary Anthropology. "It is also striking that two genetic variants inherited from Neandertals influence COVID-19 outcomes in opposite directions. Their immune system obviously influences us in both positive and negative ways today."

The ongoing fight of science against cancer has made great strides, but cancer cells have not made it easy. The complexity of cancer cells and their adaptive evolutionary nature complicate the search for effective cures. Multiple DNA repair pathways in healthy cells typically work to rectify DNA damages caused by sources within the organism, like spontaneous DNA mutations, or from outside, like ultraviolet radiation.

But what happens when these pathways malfunction? It is known that deficiencies in these pathways increase the instability of the genes, and this causes cancer to develop. Therefore, detailed knowledge of how DNA repair pathways participate in this process is crucial for tracking tumor progression, understanding the emergence of drug resistance, and developing efficient therapeutic interventions.

To this end, a group of scientists from China examined five critical DNA repair pathways and their impact on cancer evolution by reviewing the findings of the latest published research. "Different types of DNA damages have corresponding repair pathways to efficiently fix them," says Dr. Jiadong Wang, associated with Peking University Health Science Center and a member of the research team. "So, it is not surprising that particularly defective DNA repair pathways are associated with specific cancers."

They first looked at the mismatch repair system, which eliminates spontaneous mutations to ensure accurate DNA replication. A deficiency in this system, it was found, causes microsatellite instability (MSI), wherein nucleotides, the building-block components of DNA, are either longer or shorter in crucial genes, compared to the normal size, and continue replicating beyond their limit. MSI is clinically associated with 10-15% of colorectal, ovarian, endometrial, and gastric cancers.

Next on their checklist was the nucleotide excision repair (NER) pathway, which recognizes and repairs a wide range of structurally unrelated DNA lesions caused by DNA structural damage. Besides increasing the risk of bladder and breast cancers, an NER deficiency can cause Cockayne syndrome and xeroderma pigmentosum, an ultraviolet light-induced genetic disorder that causes many types of skin cancer.

The base excision repair (BER) pathway, on the other hand, repairs DNA "base lesions" that inhibit cell growth. These lesions are caused by spontaneous DNA decay and external factors like radiation and cytostatic drug treatment. BER pathway components and their deficiency are associated with a high risk of lung, pancreatic, and breast cancers.

Double-strand breaks (DSBs), caused by DNA replication or ionizing radiation, can lead to point mutations, chromosomal rearrangements, and cell death. Two pathways exist to repair DSBs--homologous recombination (HR) and non-homologous end joining. The inactivation of DSB repair genes is closely associated with cancer, and a large fraction of hereditary breast, ovarian, and prostate cancers is caused by BRCA1 and BRCA2 mutations--which are key players in the HR pathway.

Lastly, the scientists discussed the interstrand crosslink (ICL) repair pathway. ICLs, formed from aldehydes and chemotherapy drugs within the body, block essential cellular processes like replication and transcription. They are repaired by the Fanconi anemia (FA) pathway; a defect in this pathway leads to genomic instability, bone marrow failure, and an increased risk of breast and ovarian cancers.

The review combines all these findings, previously scattered across different research papers, and takes them ahead to discuss clinical interventions that could address such pathway damage. Many potential suggestions, ranging from the use of chromatin-modifying agents to the combined application of chemotherapy/radiotherapy with immune checkpoint blockade therapy, have been suggested.

Dr. Ning Zhang, another member of the team, is optimistic that knowing more about DNA repair pathways could be one of the elusive keys to curing cancer. "Specifically, the relationship between DNA repair pathways and cancer evolution need to be explored, because we have seen how closely connected the two are," he says.

Cancer has persisted for so long because of its resilient strategies to live on despite the best efforts of medicine. Perhaps this close look at the role of DNA repair pathways will arm us with another valuable weapon in the fight against cancer.

Of the nine treatments and preventives for COVID-19 authorized for emergency use by the Food and Drug Administration, three are drugs made from so-called monoclonal antibodies. Such drugs provide patients with ready-made antibodies that neutralize the virus, bypassing the body's slower and sometimes less effective process of making its own antibodies.

But such therapies were developed without detailed information about how antibodies interact with the rest of the immune system during COVID-19. Faced with a new, deadly and fast-spreading disease, drug designers started work without knowing whether antibodies' ability to activate a variety of immune cells would aid or hinder efforts to control the disease. Such abilities are collectively known as antibody effector functions.

A new study from researchers at Washington University School of Medicine in St. Louis has shown that antibody effector functions are a crucial part of effectively treating infections with SARS-CoV-2 -- the virus that causes COVID-19 -- but are dispensable when the antibodies are used to prevent infection. The findings, available online in the journal Cell, could help scientists improve the next generation of antibody-based COVID-19 drugs.

"Some of the companies removed the effector functions from their antibodies, and other companies are trying to optimize the effector functions," said senior author Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine. "Neither of these strategies is backed by data in the context of SARS-CoV-2 infections. Based on our findings, if you have a potently neutralizing antibody without effector functions and you give it before infection, as a preventive, it will probably work. But if you give it after infection, it won't work well; you need to optimize effector functions to get maximal benefit."

Antibodies are shaped like the letter Y. The tips of the two short arms are almost infinitely changeable, giving antibodies the ability to recognize virtually any molecular shape. The short arms attach to foreign molecules and target them for clearance. The long arm is where the effector functions are located. It attaches to receptors on immune cells, inducing them to kill infected cells and release molecules that sculpt the immune response.

But this process can go wrong. In a process known as antibody-dependent enhancement, interactions between the long arm of antibodies and immune cells can worsen some viral infections, notably infections with the tropical dengue virus. People who have antibodies against one strain of dengue virus are at risk of developing life-threatening dengue fever if they become infected with another strain of the virus.

To avoid the danger of antibody-dependent enhancement, some companies developing antibody-based COVID-19 drugs changed the sequence in the long arm of the antibodies to prevent it from interacting with immune cells. Other companies took the opposite tack: strengthening antibody effector functions to potentially boost the potency of their drugs.

To determine the role of antibody effector functions in COVID-19, Diamond and colleagues, including first author Emma Winkler, an MD/PhD student in Diamond's lab, and co-senior author James E. Crowe Jr., MD, of Vanderbilt University Medical Center, started with an antibody that is very effective at recognizing and neutralizing SARS-CoV-2. They eliminated the antibody's effector functions by mutating its long arm so that it could not stimulate immune cells.

The researchers gave separate groups of mice the original or the mutated SARS-CoV-2 antibodies, or a placebo antibody that does not recognize SARS-CoV-2. The antibodies were given to the animals one day before they were infected through the nose with the virus that causes COVID-19. Regardless of whether the effector functions of the antibodies were intact, the SARS-CoV-2 antibodies protected the mice against disease. Mice that had received either of the SARS-CoV-2 antibodies lost less weight and had lower levels of virus in their lungs than the ones that received the placebo antibody. Importantly, there was no sign of antibody-dependent enhancement of disease.

Then, the researchers investigated whether antibody effector functions are needed for treatment after infection. They gave mice the virus that causes COVID-19 and treated them one, two or three days later with the original or mutated SARS-CoV-2 antibodies, or a placebo antibody. Compared to the placebo, the original SARS-CoV-2 antibody protected mice against weight loss and death, but the one without effector functions did not.

Further experiments with different antibodies with and without effector functions, and in a different animal -- hamsters -- yielded the same result: Effector functions are an indispensable part of effective antibody treatment for COVID-19.

Some antibody-based drugs for COVID-19 are being developed as preventives for use in high-risk environments such as nursing homes. But most such drugs are geared toward treating people who are already infected. For that purpose, optimizing antibody effector functions could be the key to making a powerful drug, Diamond said. As part of this study, the researchers discovered that the loss of effector functions changed the kinds of immune cells that were recruited to fight the infection and how they behaved.

"'Effector functions' refers to a complex set of interactions between antibodies and other elements of the immune system," said Diamond, who also is a professor of molecular microbiology and of pathology & immunology. "You can introduce different point mutations to augment certain kinds of effector functions, and some might be harmful to the immune response while others might be beneficial. There's a lot of nuance. We are still learning how to harness effector functions so you get what you want but not what you don't want."

ITHACA, N.Y. - Working with a "star" employee - someone who demonstrates exceptional performance and enjoys broad visibility relative to industry peers - offers both risks and rewards, according to new research from the Cornell University's ILR School.

In collaborations, stars tend to get more than their share of the credit when things go well - and more of the blame when projects don't succeed, according to "Shadows and Shields: Stars Limit Their Collaborators' Exposure to Attributions of Both Credit and Blame," published Dec. 10, 2020, by Personnel Psychology.

"We look at what happens when you collaborate with a star in terms of whose getting credit when that collaboration is successful," said Rebecca Kehoe, associate professor of human resource studies. "What we find, and this is consistent with research on the Matthew effect and other work, is that if you collaborate with a star and that collaboration is successful, the star does get more of that credit and you benefit less than if you were working with somebody that wasn't a star. The silver lining here though is that if you collaborate with a star and that collaboration is not successful, the star takes the heat."

Looking at the U.S. hedge fund industry, Kehoe and her co-author, F. Scott Bentley of Binghamton University, hypothesized two-way interactions predicting that collaboration with a star would weaken both the positive effect of co-managed fund success and the negative effect of co-managed fund failure on a non-star.

The duo also examined the role a non-star's personal status plays in shaping the effects of succeeding or failing with a star co-manager. Namely, if a non-star has success of their own, they may be less likely to be overshadowed by a star co-manager when they succeed, and be better poised to benefit from shifts of blame to a star co-manager if they fail.

The paper "really points to the richness that stars can provide to an organization if they, and the people around them, are managed effectively," Kehoe said.

Kehoe and Bentley tested their hypotheses using data obtained from Eurekahedge, a private third-party investment research firm specializing in compiling data on hedge funds and fund managers, and from Institutional Investor, a media organization known for its trade journal that publishes lists ranking hedge fund firms and fund managers.

Their data consisted of monthly observations on U.S. hedge funds from 2005 to 2019 and career histories of the managers of these funds. The full dataset included information on 59,337 non-star fund managers involved in the management of 28,304 funds.

Results showed that collaborating with a star reduces the credit - and gains in professional status - that non-stars experience in the context of collaborative success. On the other hand, collaborating with a star not only mitigates - but may actually outweigh - the professional status loss associated with collaborative failure.

The duo also found that people who don't do well on their own but have a successful collaboration with a star, actually fare worse.

"They may be seen as riding the coattail of the stars," Kehoe said. "While low-performing employees might not get a status bump when they succeed with a star, if they're at least in a situation where they're learning from the star's expertise, then that's going to help their performance outside the collaboration, which can eventually put them in a better position down the line.

"I think what this points to, both for low-performing employees and for managers," she said, "is the importance of being very mindful of what is the gain that you're hoping to achieve from a collaboration with a star."

The researchers analysed cells, mouse models, and human patient samples using biochemical, mathematical, and biophysical methods. They identified a protein present in the mesh-like membrane structure (the basement membrane) associated with tumour and vessel softness, and good survival of cancer patients. The researchers tested if removing this protein from the basement membrane would enhance the spread of cancer, which it did, and if supply of this protein would reduce cancer spread, which it did. They proceeded to show that the levels of this protein (netrin-4) already present in basement membrane of organs may determine cancer spread even before cancer develops, in several cancer types.

"These are extremely exciting findings that open up the possibility to predict which organs a person's cancer most probably spread to before they even have cancer. This information therefore has the potential to guide and improve cancer patient treatment and care." said Professor Janine Erler, senior researcher on the paper.

In their study, the researchers could show for the first time the impact of basement membrane composition on its mechanical properties thereby affecting cancer cell transmigration over this protein border within the inter-cellular space. They identified the secreted protein netrin-4 to open nodes inside the basement membrane network, which simultaneously softens the basement membrane and increases its mesh (pore) size. This unexpected finding highlights that cancer cell movement is dominantly controlled by the basement membrane stiffness and pore size plays an underpart. Thus, the more netrin-4 inside the basement membrane of the primary tumour or inside blood vessels within organs prone to metastasis, the less metastasis, impacting on patient survival. Moreover, they demonstrate for the first time that the mechanical properties of the basement membrane independent of cancer-related modifications are a pivotal determinant of cancer patient survival.

"We were incredibly excited to find a mechanistic explanation for our observations where the theoretical modelling closely matched our experimental data. We could show that the more netrin-4 molecules present, the softer the basement membrane and the more difficult for a cell to traverse this membrane thereby keeping cells contained in one area. We are currently exploring the therapeutic and diagnostic potential of our findings. Our study is a result of a huge collaboration effort from researchers in Denmark, Sweden, Germany, the UK, and Belgium, spanning many disciplines, which has been key to obtaining the exciting results." added Dr Raphael Reuten, lead researcher on the study.

Historically, there has been much focus on the stiffness of the extracellular matrix that lies outside of cells and the influence on cancer progression. However, there have not been studies investigating the influence of basement membrane stiffness. Moreover, studying the impact of mechanical properties of the basement membrane on cell invasion and cancer metastasis has not been possible so far. The mechanistic insights into netrin-4 activity inside basement membranes has enabled the researchers to bridge this gap of knowledge and present new opportunities to study basement membrane stiffness in a broad range of biological processes.

Cells of organisms are organized in subcellular compartments that consist of many individual molecules. How these single proteins are organized on the molecular level remains unclear, because suitable analytical methods are still missing. Researchers at the University of Münster together with colleagues from the Max Planck Institute of Biochemistry (Munich, Germany) have established a new technique that enables quantifying molecular densities and nanoscale organizations of individual proteins inside cells. The first application of this approach reveals a complex of three adhesion proteins that appears to be crucial for the ability of cells to adhere to the surrounding tissue. The research results have been published in the journal Nature Communications.

Background and methodology

The attachment of cells is mediated by multi-molecular adhesion complexes that are built by hundreds of different proteins. The development of super-resolution microscopy, which was honoured with the Nobel Prize in 2014, allowed the identification of basic structural elements within such complexes. However, it remained unclear how individual proteins assemble and co-organize to form functional units. The laboratories of Prof. Dr. Carsten Grashoff at the Institute of Molecular Cell Biology (University of Münster) and Prof. Dr. Ralf Jungmann at the Max Planck Institute of Biochemistry (Munich) now developed a novel approach that allows the visualization and quantification of such molecular processes even in highly crowded subcellular structures.

"A substantial limitation even of the best super-resolution microscopy techniques is that many molecules remain undetected. It is therefore nearly impossible to make quantitative statements about processes of molecular complex formation in cells", explains Lisa Fischer, PhD student in the Grashoff group and first author of the study. This difficulty could now be circumvented with a combination of experimental controls and theoretical considerations.

"By applying our new analytical method, we were able to provide evidence for the existence of a long suspected ternary adhesion complex. We knew already before that each of these three molecules is very important for cell adhesion", explains Fischer. "However, it was not clear whether all three proteins come together to form a functional unit". As the method is broadly applicable, the researchers believe that many other cellular processes will be studied with the new analysis procedure.

The risk of both mortality and rehospitalisation after an elective revascularisation procedure for coronary artery disease is similar for people with and without Alzheimer's disease (AD), but people with AD had worse outcomes after an emergency procedure, according to a new study from the University of Eastern Finland.

Previous studies have investigated the effectiveness of revascularisation in persons with cognitive disorders, but only in terms of short-term outcomes and in acute care settings, and they also have not accounted for electivity. Similar to previous studies, people with Alzheimer's disease were 76% less likely to undergo a revascularisation procedure and only a third of the procedures were elective, compared to 48.6% of elective procedures in the comparison group without AD.

People with Alzheimer's disease had a higher risk of mortality in the procedural unit, and a 1.42-fold mortality rate during a 3-year follow-up, compared to people without AD. However, the risks were similar for elective procedures in persons with and without AD. Sociodemographic characteristics, comorbidities, statin use, length of stay and required support at discharge were controlled for in the analyses. The results were similar for both revascularisation procedure types studied, i.e., coronary artery bypass graft surgery (CABG) and percutaneous coronary interventions (PCI).

These observations on a lower rate for elective revascularisations and comparable outcomes after revascularisation procedures indicate a different threshold for elective procedures compared to emergency ones, and a very different selection for people with major cognitive disorders.

The study was conducted as part of the Medication Use and Alzheimer's Disease Study (MEDALZ), in a cohort which includes 70,718 Finnish community dwellers with Alzheimer's disease, and a matched comparison cohort. This study was restricted to people who had no previous revascularisation.

New analysis published in The Lancet Psychiatry has shown a lack of strong evidence to support current guidance on psychological therapies for treating anorexia nervosa over expert treatment as usual.

The findings highlight a need for further research and support a call for individual trial data to be made available so the benefits of treatments in specific patient populations can be better understood.

Conducted by an international team of clinical experts and researchers, the analysis included 13 randomised controlled trials and a total of 1049 patients. The studies compared psychological therapies to treatment as usual in adults receiving outpatient treatment for anorexia. The trials measured eating disorder symptoms, body-mass index (BMI) and all-cause dropout rate up to 52 weeks of follow up.

The analysis found some therapies to have modest benefit to patients. However, the therapies, currently recommended by the National Institute for Clinical Excellence (NICE) and in clinical guidelines internationally, were not shown to differ significantly from expert treatment as usual.

Professor Andrea Cipriani (University of Oxford), lead author on the project, says:

"Understanding the effectiveness of available treatments is particularly important for anorexia nervosa because it has one of the highest mortality rates of any psychiatric condition. This analysis highlights the gaps in existing evidence and the urgent need for more and better research into psychological therapies for treating Anorexia."

Because of the relatively low quality and quantity of data available, this analysis should be understood as exploratory rather than confirmatory. However, it highlights the shortcomings of existing research and emphasises the need for more robust data.

Professor Tracey Wade (Flinders University), lead collaborator on the project, says:

"We have made progress in understanding the effective non-specific factors that need to be included in any treatment for anorexia nervosa. Our future challenge is to develop treatment factors tailored to individual presentations that can be added to the non-specific factors to increase effectiveness of our treatments for the condition."

The research was funded by the NIHR Oxford Health Biomedical Research Centre, the University of Oxford and Flinders University.

* The psychological interventions included in the analysis include Cognitive Behavioural Therapy (CBT), family-oriented treatments, psychodynamic treatments, and other treatments such as Maudsley anorexia nervosa treatment for adults (MANTRA) and specialist supportive clinical management (SSCM).

* Treatment at usual varied between the trials included in the analysis and can involve several components delivered by many people. The poor description of treatment as usual was a limitation observed in most of the trials included in the analysis.

The paper, Comparative efficacy and acceptability of psychological interventions for the treatment of adult outpatients with anorexia nervosa: a systematic review and network meta-analysis, published in The Lancet Psychiatry will be available here http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(20)30566-6/fulltext.

The tiniest microchips yet can be made from graphene and other 2D-materials, using a form of 'nano-origami', physicists at the University of Sussex have found.

This is the first time any researchers have done this, and it is covered in a paper published in the ACS Nano journal.

By creating kinks in the structure of graphene, researchers at the University of Sussex have made the nanomaterial behave like a transistor, and have shown that when a strip of graphene is crinkled in this way, it can behave like a microchip, which is around 100 times smaller than conventional microchips.

Prof Alan Dalton in the School of Mathematical and Physics Sciences at the University of Sussex, said:

"We're mechanically creating kinks in a layer of graphene. It's a bit like nano-origami.

"Using these nanomaterials will make our computer chips smaller and faster. It is absolutely critical that this happens as computer manufacturers are now at the limit of what they can do with traditional semiconducting technology. Ultimately, this will make our computers and phones thousands of times faster in the future.

"This kind of technology - "straintronics" using nanomaterials as opposed to electronics - allows space for more chips inside any device. Everything we want to do with computers - to speed them up - can be done by crinkling graphene like this."

Dr Manoj Tripathi, Research Fellow in Nano-structured Materials at the University of Sussex and lead author on the paper, said:

"Instead of having to add foreign materials into a device, we've shown we can create structures from graphene and other 2D materials simply by adding deliberate kinks into the structure. By making this sort of corrugation we can create a smart electronic component, like a transistor, or a logic gate."

The development is a greener, more sustainable technology. Because no additional materials need to be added, and because this process works at room temperature rather than high temperature, it uses less energy to create.

Scientists at Cardiff University have discovered a unique way to target a common virus that affects one in 200 newborn babies in the UK but for which there is only limited treatments available.

Human cytomegalovirus (HCMV) is a master at "hiding" from the body's immune system so antibodies and T-cells cannot attack it as they do in other viruses, like the current coronavirus.

The researchers have now discovered a new type of antibody in the lab which - instead of killing the virus directly - marks infected cells so the immune system can "see" them.

Once the immune system can see the infected cells it is able to kill the virus.

The team have submitted a patent for the unique immunotherapeutic and hope it can help to treat HCMV, which can leave newborn babies severely disabled or even kill them.

Further work is needed to make sure it is safe and effective in humans - but the researchers hope the technique could eventually be used to fight other infectious diseases and the method they used to find the new antibody could be applied to cancer.

The study is published today in the Journal of Clinical Investigation.

Lead author Dr Richard Stanton, a virologist from Cardiff University's Division of Infection and Immunity, said: "HCMV is a major challenge because it has evolved a range of different techniques to avoid the body's own immune response.

"We have developed a really unique way of letting the immune system see the virus so it can get on with its task of killing it."

HCMV causes lifelong infection in humans and is a significant cause of severe disease or death in immunocompromised individuals, such as those undergoing transplants or people with HIV.

A vaccine is paramount to fighting the virus, particularly for tackling congenital disease, however there is currently no vaccine and only limited treatment options are available.

In this study, the researchers looked at whether antibody-dependent cellular cytotoxicity (ADCC) - a particular type of immune response in which a target cell is coated with antibodies and killed by immune cells - could be exploited for therapeutic use.

They used a special technique (proteomics) to characterise the molecules found on the surface of the infected cell and combined this with immunological screening to identify targets for ADCC.

They found a unique target expressed early in the virus's lifecycle and were then able to develop human antibodies for use against this target.

In the lab, this brought about a potent activation of ADCC, killing the infected cells.

"The identification of novel ADCC targets not only opens up a fuller understanding of natural immunity against HCMV that can be exploited for therapeutic benefit, but this could also now be applied to other infectious diseases - and the mechanism we used to pinpoint the new antibody could potentially also work in cancer," said Dr Stanton.

"Further work is now needed to demonstrate both safety and efficacy in humans."

Researchers have used the zebrafish (Danio rerio) to identify the role of a gene involved in cardiac rhythm, which could help explain the fundamentals of what it takes to make a human heartbeat.

The University of Melbourne study also found that mutation of the gene, Tmem161b, causes potentially fatal cardiac arrhythmia. 2.5 per cent of Australians are living with cardiac arrhythmia (ABS). In 2019, it took 3090 years of potential life. Mutations in this gene may be contributing to the cause of this.

Published in Proceedings of National Academy of Sciences of the United States of America (PNAS), the research could lead to better understanding and treatment of the condition in humans.

University of Melbourne Associate Professor Kelly Smith said the research discovered what Tmem161b does, when previously we had no idea of its function.

"Zebrafish eggs were used as they have complex beating hearts, similar to humans," Associate Professor Smith said. "Eighty per cent of zebrafish genes are like ours and both use the same basic 'equipment'."

The researchers used naturally produced eggs to observe organ development under a microscope. The eggs are translucent, which allowed observation without interference.

Associate Professor Smith said this important discovery would improve our knowledge of the heartbeat.

"What's important is, it describes a new gene in cardiac rhythm, which helps us to understand the fundamentals of what it takes to make a heartbeat," Associate Professor Smith said.

"Until now, no-one has known what it does, which makes this research so exciting.

"We screened thousands of zebrafish families and found one with inherited arrhythmia. Working backwards from there, we found which gene was mutated to cause the arrhythmia. It turned out to be a gene that was completely uncharacterised."

Associate Professor Smith said she suspected the finding would be relevant in humans.

"Given the prevalence of cardiac arrhythmia in Australia, the more we know about how the heart works, the better," she said.

"The gene described in the research appears to play a central function, so we expect it to be important in more than just controlling heart rhythm. But that will take time to explore.

"If this turns out to be significant in humans, it will provide a new candidate for genetic screening of patients with cardiac arrhythmias."

Almost half of people testing positive for coronavirus have reported symptoms of depression, according to a new study published in the International Journal of Environmental Research and Public Health.

Researchers from Bangladesh, the United States and Anglia Ruskin University (ARU) in the UK carried out a cross-sectional survey of more than 1,000 Bangladeshi adult coronavirus patients over the course of one month.

A total of 48% of respondents were categorised as having moderate to severe depression, with a higher prevalence in those with persistent symptoms, low family income and poor health status.

A fifth of those surveyed reported having persistent COVID-19 symptoms, the most common of these being diarrhoea and fatigue. Around a quarter of patients had attempted to self-medicate their symptoms with over-the-counter medicines, rather than contact health services.

Co-author Professor Shahina Pardhan, of Anglia Ruskin University, said: "Our study found a high number of respondents suffering depression alongside their COVID-19 symptoms, particularly those who were more vulnerable.

"We know that the World Health Organisation has reported that mental health services across the world have been disrupted by the pandemic, and this study shows the pressing need for these services among those testing positive for the virus."

Researchers from North Carolina State University, Boston University and Kraton Corporation have demonstrated a family of self-sterilizing polymers that are effective at inactivating coronaviruses, including SARS-CoV-2 - the virus that causes COVID-19. The work opens the door to a suite of applications that could help to reduce the transmission of COVID-19 and other diseases.

"Our work here provides conclusive evidence that these materials, anionic polymers, can inactivate human coronaviruses quickly and efficiently," says Richard Spontak, co-author of a paper on the work accepted for publication in Advanced Science. Spontak is a Distinguished Professor of Chemical and Biomolecular Engineering and a professor of materials science and engineering at North Carolina State University.

"If we want to coat high-contact surfaces such as textiles, countertops or walls - it's possible," says Frank Scholle, co-author of the paper and an associate professor of biological sciences at NC State. "Virus inactivation will occur as long as there is sufficient humidity," adds Scholle, who is also director of NC State's Center for Advanced Virus Experimentation (CAVE).

When these anionic polymers absorb water, protons can travel through nanoscale channels to the surface, creating a highly acidic environment capable of inactivating viruses and killing bacteria and mold. The research team had previously demonstrated that several of the anionic polymers were effective against a range of pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and a strain of influenza.

"Based on what we've learned, we've been able to identify a fundamentally new inactivation mechanism and a family of polymers that expands the health care sector's arsenal for fighting the spread of coronavirus," Spontak says.

In laboratory experiments, the researchers demonstrated that specific anionic polymers could fully inactivate SARS-CoV-2 in just 5 minutes, and fully inactivate a human coronavirus surrogate called HCoV-229E in 20 minutes.

Kraton Corporation is in the process of evaluating applications for how some of these polymers might be used in a variety of settings.

"We are thankful for the opportunity to collaborate with NC State University and Boston University to address an important and urgent need for long-lasting antimicrobial performance," says Vijay Mhetar, Kraton's Chief Technology Officer. "Building upon this scientific discovery, Kraton Corporation is actively seeking regulatory approvals and evaluating application uses in transportation, health care, and building and infrastructure."