Culture

The clinical presentation of Covid-19 varies from patient to patient and understanding individual genetic susceptibility to the disease is therefore vital to prognosis, prevention, and the development of new treatments. For the first time, Italian scientists have been able to identify the genetic and molecular basis of this susceptibility to infection as well as to the possibility of contracting a more severe form of the disease. The research will be presented to the 53rd annual conference of the European Society of Human Genetics, being held entirely on-line due to the Covid-19 pandemic, today [Saturday].

Professor Alessandra Renieri, Director of the Medical Genetics Unit at the University Hospital of Siena, Italy, will describe her team's GEN-COVID project to collect genomic samples from Covid patients across the whole of Italy in order to try to identify the genetic bases of the high level of clinical variability they showed. Using whole exome sequencing (WES)1 to study the first data from 130 Covid patients from Siena and other Tuscan institutions, they were able to uncover a number of common susceptibility genes that were linked to a favourable or unfavourable outcome of infection. "We believe that variations in these genes may determine disease progression," says Prof Renieri. "To our knowledge, this is the first report on the results of WES in Covid-19."

Searching for common genes in affected patients against a control group did not give statistically significant results with the exception of a few genes. So the researchers decided to treat each patient as an independent case, following the example of autism spectrum disorder. "In this way we were able to identify for each patient an average of three pathogenic (disease-causing) mutations involved in susceptibility to Covid infection," says Prof Renieri. "This result was not unexpected, since we already knew from studies of twins that Covid-19 has a strong genetic basis."

Although presentation of Covid is different in each individual, this does not rule out the possibility of the same treatment being effective in many cases. "The model we are proposing includes common genes and our results point to some of them. For example, ACE2 remains one of the major targets. All our Covid patients have an intact ACE2 protein, and the biological pathway involving this gene remains a major focus for drug development," says Prof Renieri. ACE2 is an enzyme attached to the outer surface of several organs, including the lungs, that lowers blood pressure. It serves as an entry point for some coronaviruses, including Covid-19.

These results will have significant implications for health and healthcare policy. Understanding the genetic profile of patients may allow the repurposing of existing medicines for specific therapeutic approaches against Covid-19 as well as speeding the development of new antiviral drugs. Being able to identify patients susceptible to severe pneumonia and their responsiveness to specific drugs will allow rapid public health treatment interventions. And future research will be aided, too, by the development of a Covid Biobank accessible to academic and industry partners.

The researchers will now analyze a further 2000 samples from other Italian regions, specifically from 35 Italian Hospitals belonging to the GEN-COVID project.2

"Our data, although preliminary, are promising, and now we plan to validate them in a wider population," says Prof Renieri. "Going beyond our specific results, the outcome of our study underlines the need for a new method to fully assess the basis of one of the more complex genetic traits, with an environmental causation (the virus), but a high rate of heritability. We need to develop new mathematical models using artificial intelligence in order to be able to understand the complexity of this trait, which is derived from a combination of common and rare genetic factors.

"We have developed this approach in collaboration with the Siena Artificial Intelligence Lab, and now intend to compare it with classical genome-wide association studies3 in the context of the Covid-19 Host Genetics Initiative, which brings together the human genetics community to generate, share, and analyse data to learn the genetic determinants of COVID-19 susceptibility, severity, and outcomes. As a research community, we need to do everything we can to help public health interventions move forward at this time."

Chair of the ESHG conference, Professor Joris Veltman, Dean of the Biosciences Institute at Newcastle University, Newcastle upon Tyne, UK, said: "We are very excited to have this work on the genetics of COVID19 susceptibility presented as one of our late-breaking abstract talks at the ESHG. Our Italian colleagues present the first insight into the role of genetic susceptibility influencing the severity of the response to a COVID19 infection. It needs to be expanded to encompass much larger populations, but it is impressive to see the speed at which research on this virus has proceeded in just a few months' time."

A research team from Genethon, in collaboration with teams from CNRS/Inserm and from the biotechnology company Spark Therapeutics, announced today in Nature Medicine that it has succeeded in inhibiting the immune response induced by AAV antibodies present as a result of natural immunity or following gene therapy, thanks to the IdeS enzyme. This result opens up new therapeutic prospects and the possibility of treating more patients.

Gene therapy consists of injecting a therapeutic gene into an organism using a vector, a "means of transport" able to cross all biological barriers through the cell and into the nucleus. The most commonly used vectors are derived from viruses, such as AAVs (adeno-associated viruses), used particularly in gene therapy targeting the muscles, liver, eyes, etc. In many cases, once it comes into contact with this virus, the body develops immunoglobulins (IgG) known to be neutralising, i.e. specific antibodies that inhibit AAVs. It is considered that between 30% and 50% of humans are naturally immunized against most AAVs used for therapeutic purposes. As a result, a large number of patients cannot currently benefit from AAV gene therapy. Moreover, a first injection of an AAV leads to an immune response against the vector, precluding any subsequent AAV gene therapy.

Overcoming this impediment is an essential factor in treating the maximum number of patients. Therefore, the teams lead by Giuseppe Ronzitti, a Genethon researcher, Sébastien Lacroix-Desmazes, a CNRS-Inserm researcher, and Federico Mingozzi from the biotechnology company Spark Therapeutics, have used animal models to test the efficacy of the IdeS enzyme, an endopeptidase that naturally reduces the action of antibodies, in order to neutralise the immune response due to IgG immunoglobulins.

The study was carried out in two steps:
Researchers injected the IdeS enzyme into subjects with neutralizing anti-AAV IgG before injecting the gene therapy vector of the same serotype and then observed that the IdeS treatment neutralized the action of the antibodies. This first step provided proof of the efficacy of this approach for subjects with natural immunity.

Then, the teams tested this approach with a view to the possible reinjection of gene therapy drugs. So, they administered a first dose of AAV vector, then a second dose after injection of IdeS. They observed that IdeS, by reducing the level of circulating antibodies, allowed the re-administration of the vector.

These two studies demonstrate that treatment with IdeS allows repeated administration of AAV gene therapy. This is a significant and promising step forward in the treatment of rare genetic diseases because, if the efficacy of this technique is confirmed in humans, it will make it possible to treat patients at the first signs of the disease and to re-inject a gene therapy product if necessary.

"These studies should enable us to test this innovative approach in humans and thus, in the long term, to give AAV-positive patients the possibility of benefiting from gene therapy, despite the presence of antibodies. This could also make it possible to treat patients as soon as the first symptoms of the disease appear (affecting the liver, for example) and, if necessary, to re-administer the gene therapy treatment in an effective manner," stresses Christian Leborgne, research engineer at Genethon.

"This study represents an important step towards solving a complex and fundamental problem, namely the repeated administration of gene therapy treatments to patients who may need them, and also the treatment of patients who today are not eligible for gene therapy due to the existence of neutralizing antibodies in their systems. This study highlights, once again, the expertise of our researchers, who are imagining and developing new approaches to make gene therapy even more effective and to increase the number of patients able to access it," says Frédéric Revah, Chief Executive Officer of Genethon.

n 2017 and 2019, the German Institute for Quality and Efficiency in Health Care (IQWiG) had already examined the advantages and disadvantages of ribociclib in combination with an aromatase inhibitor or fulvestrant in comparison with the appropriate comparator therapy in patients after menopause, with hormone receptor-positive, HER2-negative, locally advanced or metastatic breast cancer. Since the assessments were based on ongoing studies, the Federal Joint Committee (G-BA) had limited its corresponding decisions.

After expiry of the decisions, IQWiG now reassessed the combinations on the basis of further data from the same studies. According to the findings, an added benefit is not proven for initial endocrine therapy with ribociclib in combination with the aromatase inhibitor letrozole and for subsequent endocrine therapy with ribociclib plus fulvestrant. For initial endocrine therapy with ribociclib plus fulvestrant, in contrast, there is now an indication of a minor added benefit.

Newer data confirm survival advantages, but also severe side effects

In the first assessment conducted in 2017, on the basis of the data from the ongoing MONALEESA-2 study available at that time, the Institute found the drug in combination with an aromatase inhibitor to have lesser benefit than the comparator therapy due to partly very severe side effects. In 2019, the survival advantage for the combination with fulvestrant shown in the also still ongoing MONALEESA-3 was outweighed by the severe side effects; the resulting conclusion was therefore: An added benefit is not proven.

The new data cut-offs from both studies now confirmed the survival advantages for the combination with fulvestrant, and for the first time showed survival advantages for the combination with an aromatase inhibitor, but also confirmed the major disadvantages: Women treated with ribociclib developed severe side effects much more frequently than study participants in the comparator arms of the studies, particularly severe neutropenia. This means that the number of neutrophil granulocytes - immune cells which are essential for fighting infection - in their blood was too low.

In initial endocrine therapy for the advanced stage, these negative effects did not completely call into question the survival advantage of ribociclib plus fulvestrant versus placebo plus fulvestrant, but they resulted in a downgrading of the extent of the added benefit. An indication of a minor added benefit remained.

An added benefit is not proven for two of three research questions

In women who have already received endocrine therapy for the advanced stage, there was no statistically significant advantage in overall survival under ribociclib plus fulvestrant; this was only shown if results of the total study - including patients without pretreatment - were additionally taken into account. This and the major positive effect for emotional functioning in the outcome category "health-related quality of life" (but only for patients aged 65 years and older) did not have greater weight in the assessment than the mostly severe side effects of considerable or major extent, so that an added benefit is not proven for these patients.

Both positive and negative effects were also shown for the combination of ribociclib and the aromatase inhibitor letrozole in comparison with placebo and letrozole. The advantages in overall survival and future perspective (another aspect of the outcome category "health-related quality of life") and the disadvantages in severe side effects (besides the already mentioned neutropenia, also gastrointestinal disorders, infections and infestations) balanced each other out; an added benefit is not proven also in this case.

G-BA decides on the extent of added benefit

The dossier assessments are part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the G-BA. After publication of the dossier assessments, the G-BA conducts commenting procedures and makes decisions on the extent of the added benefit.

More English-language information will be available soon (extracts of the dossier assessments as well as easily understandable information on informedhealth.org). If you would like to be informed when these documents are available, please send an e-mail to info@iqwig.de.

What The Study Did: The clinical characteristics and outcomes of patients who received intervention by a COVID-19 palliative care response team are examined in this case series.

Authors: Shunichi Nakagawa, M.D., of the Columbia University Medical Center in NewYork, is the corresponding author.

To access the embargoed study:  Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2020.2713)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

MEDFORD/SOMERVILLE, Mass. (June 5, 2020)--Researchers at Tufts University's School of Engineering have developed biomaterial-based inks that respond to and quantify chemicals released from the body (e.g. in sweat and potentially other biofluids) or in the surrounding environment by changing color. The inks can be screen printed onto textiles such as clothes, shoes, or even face masks in complex patterns and at high resolution, providing a detailed map of human response or exposure. The advance in wearable sensing, reported in Advanced Materials, could simultaneously detect and quantify a wide range of biological conditions, molecules and, possibly, pathogens over the surface of the body using conventional garments and uniforms.

"The use of novel bioactive inks with the very common method of screen printing opens up promising opportunities for the mass-production of soft, wearable fabrics with large numbers of sensors that could be applied to detect a range of conditions," said Fiorenzo Omenetto, corresponding author and the Frank C. Doble Professor of Engineering at Tufts' School of Engineering. "The fabrics can end up in uniforms for the workplace, sports clothing, or even on furniture and architectural structures."

Wearable sensing devices have attracted considerable interest in monitoring human performance and health. Many such devices have been invented incorporating electronics in wearable patches, wristbands, and other configurations that monitor either localized or overall physiological information such as heart rate or blood glucose. The research presented by the Tufts team takes a different, complementary approach - non-electronic, colorimetric detection of a theoretically very large number of analytes using sensing garments that can be distributed to cover very large areas: anything from a patch to the entire body, and beyond.

The components that make the sensing garments possible are biologically activated silk-based inks. The soluble silk substrate in these ink formulations can be modified by embedding various "reporter" molecules - such as pH sensitive indicators, or enzymes like lactate oxidase to indicate levels of lactate in sweat. The former could be an indicator of skin health or dehydration, while the latter could indicate levels of fatigue of the wearer. Many other derivatives of the inks can be created due to the versatility of the silk fibroin protein by modifying it with active molecules such as chemically sensitive dyes, enzymes, antibodies and more. While the reporter molecules could be unstable on their own, they can become shelf-stable when embedded within the silk fibroin in the ink formulation.

The inks are formulated for screen printing applications by combining with a thickener (sodium alginate) and a plasticizer (glycerol). The screen printable bio-inks can be used like any ink developed for screen printing, and so can be applied not just to clothing but also to various surfaces such as wood, plastics and paper to generate patterns ranging from hundreds of microns to tens of meters. While the changes in color presented by the inks can provide a visual cue to the presence or absence of an analyte, use of camera imaging analysis scanning the garments or other material can gather more precise information on both quantity and high resolution, sub-millimeter mapping.

The technology builds upon earlier work by the same researchers developing bioactive silk inks formulated for inkjet-printing to create petri dishes, paper sensors, and laboratory gloves that can indicate bacterial contamination by changing colors.

"The screen printing approach provides the equivalent of having a large, multiplexed arrangement of sensors covering extensive areas of the body, if worn as a garment, or even on large surfaces such as room interiors," said Giusy Matzeu, research assistant professor of biomedical engineering at Tufts School of Engineering and first author of the paper. "Coupled with image analysis, we can obtain a high resolution mapof color reactions over a large area and gain more insight on overall physiological or environmental state. In theory, we could extend this method to track air quality, or support environmental monitoring for epidemiology."

The fact that the method uses common printing techniques also opens up avenues in creative applications - something explored by Laia Mogas-Soldevila, architect and recent PhD graduate at Tufts in Omenetto's SilkLab. Mogas-Soldevila has helped to create beautiful tapestries, displaying them in museums across the United States and Europe. The displays are interactive, allowing visitors to spray different, non-toxic chemicals onto the fabric and watch the patterns transform. "This is really a great example of how art and engineering can gain from and inspire each other," said Mogas-Soldevila. "The engineered inks open up a new dimension in responsive, interactive tapestries and surfaces, while the 1,000-year old art of screen printing has provided a foundation well suited to the need for a modern high resolution, wearable sensing surface."

A research group led by the University of Bologna identified a new mechanism that allows to obtain serological tests that are quicker, more cost-effective and more reliable than those currently in use. This mechanism is based on the technique of electrochemiluminescence (ECL) and is applicable to serological tests devised to detect the antibodies against SARS-CoV-2. The future of this innovative technique is an industrial application, as two leading firms in the fields of diagnostics and technologies, were also involved in this research: the Germany-based Roche Diagnostic and the Japanese Hitachi High Tech.

The study was published on Nature Communications and its outcomes show serological tests with increased sensitivity levels up to 128% more than those currently in use is possible thanks to highly efficient reactants.

"The results we obtained mark a new milestone in the state of the art of signal enhancement of ECL-based immunoassays", says Francesco Paolucci leader of the research group and professor at the University of Bologna. "This milestone is the outcome of years and years of international research into electrochemistry and of a close synergy with R&D sectors".

Serological tests are based on the ability to translate into measurable and visible signals the interactions between some molecules and the antibodies the test intends to quantify. ECL can play a major role here, as it relies on an electrochemical reaction producing a light signal. In the case of serological tests, electrochemiluminescence "switches on" the antibodies as if they were lamps.

This mechanism has, however, some limitations: the molecules that are able to prompt this reaction are in very low concentrations in the human blood. Therefore, we need highly-sensitive techniques to identify the antibodies in the blood. The results obtained by this research group seems to go exactly in this direction.

"Our work represents something unprecedented in the field of ECL because it relies on the enhancement of the signal as opposed to the enhancement of the target as it usually happens with enzymatic methods or PCR (Polymerase Chain Reaction)", explains Giovanni Valenti, study coordinator and researcher at the University of Bologna. "These results pave the way for the development of ultra-sensitive serological tests".

The researchers obtained a twofold result with this study. On the one hand, they refined the mechanisms regulating ECL analyses; on the other hand, they employed these mechanisms to develop new reactants that allow to obtain far more efficient serological tests.

"From these results, we managed to identify highly efficient reactants that are able to enhance the sensitivity of this technique way beyond that currently employed for serological tests", confirms Alessandra Zanut, first author of the study and researcher at the University of Bologna. "With this technique, we obtained an ECL signal enhancement up to 128% compared to current techniques".

Sometimes toxins, such as hazardous wastes and industrial byproducts, seep into groundwater, the source of our drinking water. One such pollutant is perchlorate, a chemical compound used in rocket fuels, fireworks, fertilizers and other materials. The compound is thought to contribute to health issues in humans such as hypothyroidism, the decreased production of hormones from the thyroid gland, which can impact development.

The findings, they say, suggest that an acceptable safe concentration of perchlorate in drinking water is 10 times less than previously thought.

The researchers focused on how perchlorate blocks a main route by which iodide, the negatively charged form of the element iodine, enters thyroid cells. Iodide helps the thyroid make hormones that are essential to the body's regulation of metabolism, temperature and other important functions.

Thyroid cells control the incoming flow of iodide by using a protein channel called the sodium/iodide symporter, also known as the Na+/I- symporter or NIS. Like other cellular transport systems, a "lock-and-key" approach is used to move iodide, with NIS acting as the lock and sodium as the key. Sodium fits into NIS at two binding sites to unlock the channel, enabling iodide to pass through and accumulate inside a thyroid cell.

The team, led by L Mario Amzel, Ph.D., professor of biophysics and biophysical chemistry at the Johns Hopkins University School of Medicine, and Vanderbilt University researcher Nancy Carrasco, M.D., determined that perchlorate blocks the channel by latching onto the NIS protein and changing its shape. Less sodium binds to the misshaped channel, thereby significantly lowering the amount of iodide that can be moved inside thyroid cells.

The researchers studied how varying concentrations of perchlorate affects iodide transport by first growing thyroid cells that expressed the gene SLC5A5, which encodes the instructions for building NIS channels. Next, perchlorate and radioactive iodine were placed outside of some of the cells and just radioactive iodine outside the others. Finally, the researchers tracked how much glowing iodide was allowed to enter the cells in both groups. They found that there was much less iodide inside thyroid cells treated with perchlorate than in untreated ones, even at very low concentrations of the chemical.

In May 2020, the U.S. Environmental Protection Agency (EPA) ruled not to place regulations on the amount of perchlorate that can be allowed in drinking water. The findings from the new study strongly suggest that this environmental pollutant is more hazardous than previously thought, raising serious concern about the decision.

"We hope that these findings will prompt the EPA to change its mind," Amzel says.

Seeking to address estimates that more than a third of COVID-19 deaths nationally have occurred in nursing homes and long-term care facilities--more than 38,000 - the American Medical Directors Association published recommendations for reducing the spread of the pandemic virus among residents and staff.

Among the recommendations were the creation of COVID-specific units, screenings of residents twice daily, discontinuing of drug delivery modes (e.g. nebulizers) that might spread the virus, and reviews with patients and families of do-not-intubate and do-not-hospitalize advance directives.

"The scope and speed of the COVID-19 pandemic brought continual changes in healthcare protocols as providers learned more about the disease's transmission," said Paula Lester, MD, FACP, CMD, a geriatrician at NYU Winthrop Hospital and the corresponding author of the consensus recommendations, which were recently published online in Journal of American Medical Directors Association (JAMDA).

"The time has come to consolidate our learnings as a field in terms of caring for at-risky elderly and implement uniform, best practices, especially as we prepare for a potential second wave of infections in the coming months, as well as for future pandemics," adds Lester, who along with her co-authors, serves as a skilled nursing facility (SNF) certified medical director.

Recommended protocols for facility staff also include COVID testing on a serial basis--three tests one-week apart--to enable identification of newly infected staff. Also recommended is to have staff assigned to specific units to permit easier contact tracing in the event of COVID cases, and to have staff that are assigned to COVID-19 units not work elsewhere in the facility.

The report also states that the authors "do not support the mandatory admission of COVID-19 patients from hospitals to nursing homes as it may force unprepared facilities to provide care to COVID patients without the necessary resources or precautions."

The consensus guidelines in the report - titled "Policy Recommendations Regarding Skilled Nursing Facility Management of COVID-19: Lessons From New York State" - are endorsed by the Executive Board of the New York Medical Directors Association and the Board of the Metropolitan Area Geriatrics Society. The authors noted, however, that the suggestions in the report should not take precedence over local Department of Health or Centers for Disease Control recommendations.

Perhaps no region of the brain is more fittingly named than the claustrum, taken from the Latin word for "hidden or shut away." The claustrum is an extremely thin sheet of neurons deep within the cortex, yet it reaches out to every other region of the brain. Its true purpose remains "hidden away" as well, with researchers speculating about many functions. For example, Francis Crick of DNA-discovery fame believed that the claustrum is the seat of consciousness, responsible for awareness and sense of self.

What is known is that this region contains a large number of receptors targeted by psychedelic drugs such as LSD or psilocybin ¾ the hallucinogenic chemical found in certain mushrooms. To see what happens in the claustrum when people are on psychedelics, Johns Hopkins Medicine researchers compared the brain scans of people after they took psilocybin with their scans after taking a placebo.

Their findings were published online on May 23, 2020, in the journal NeuroImage.

The scans after psilocybin use showed that the claustrum was less active, meaning the area of the brain believed responsible for setting attention and switching tasks is turned down when on the drug. The researchers say that this ties in with what people report as typical effects of psychedelic drugs, including feelings of being connected to everything and reduced senses of self or ego.

"Our findings move us one step closer to understanding mechanisms underlying how psilocybin works in the brain," says Frederick Barrett, Ph.D., assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and a member of the school's Center for Psychedelic and Consciousness Research. "This will hopefully enable us to better understand why it's an effective therapy for certain psychiatric disorders, which might help us tailor therapies to help people more."

Because of its deep-rooted location in the brain, the claustrum has been difficult to access and study. Last year, Barrett and his colleagues at the University of Maryland, Baltimore, developed a method to detect brain activity in the claustrum using functional magnetic resonance imaging (fMRI).

For this new study, the researchers used fMRI with 15 people and observed the claustrum brain region after the participants took either psilocybin or a placebo. They found that psilocybin reduced neural activity in the claustrum by 15% to 30%. This lowered activity also appeared to be associated with stronger subjective effects of the drug, such as emotional and mystical experiences. The researchers also found that psilocybin changed the way that the claustrum communicated with brain regions involved in hearing, attention, decision-making and remembering.

With the highly detailed imaging of the claustrum provided by fMRI, the researchers next hope to look at the mysterious brain region in people with certain psychiatric disorders such as depression and substance use disorder. The goal of these experiments will be to see what roles, if any, the claustrum plays in these conditions. The researchers also plan to observe the claustrum's activity when under the influence of other psychedelics, such as salvinorin A, a hallucinogen derived from a Mexican plant.

Researchers from the Moscow Institute of Physics and Technology, joined by a colleague from Argonne National Laboratory, U.S., have implemented an advanced quantum algorithm for measuring physical quantities using simple optical tools. Published in Scientific Reports, their study takes us a step closer to affordable linear optics-based sensors with high performance characteristics. Such tools are sought after in diverse research fields, from astronomy to biology.

Maximizing the sensitivity of measurement tools is crucial for any field of science and technology. Astronomers seek to detect remote cosmic phenomena, biologists need to discern exceedingly tiny organic structures, and engineers have to measure the positions and velocities of objects, to name a few examples.

Until recently, no measurement tool could ensure precision above the so-called shot noise limit, which has to do with the statistical features inherent in classical observations. Quantum technology has provided a way around this, boosting precision to the fundamental Heisenberg limit, stemming from the basic principles of quantum mechanics. The LIGO experiment, which detected gravitational waves for the first time in 2016, shows it is possible to achieve Heisenberg-limited sensitivity by combining complex optical interference schemes and quantum techniques.

Quantum metrology is a cutting-edge area of physics concerned with the technological and algorithmic tools for making highly precise quantum measurements. In their recent study, the team from MIPT and ANL fused quantum metrology with linear optics.

"We devised and constructed an optical scheme that runs the Fourier transform-based phase estimation procedure," said study co-author Nikita Kirsanov from MIPT. "This procedure lies at the core of many quantum algorithms, including high-precision measurement protocols."

A specific arrangement of a very large number of linear optical elements -- beam splitters, phase shifters, and mirrors -- makes it possible to gain information about the geometric angles, positions, velocities as well as other parameters of physical objects. The measurement involves encoding the quantity of interest in the optical phases, which are then determined directly.

"This research is a follow-up to our work on universal quantum measurement algorithms," commented principal investigator Gordey Lesovik, who heads the MIPT Laboratory of the Physics of Quantum Information Technology. "In an earlier collaboration with a research group from Aalto University in Finland, we experimentally implemented a similar measurement algorithm on transmon qubits."

The experiment showed that despite the large number of optical elements in the scheme, it is nevertheless tunable and controllable. According to the theoretical estimates provided in the paper linear optics tools are viable for implementing even operations that are considerably more complex.

"The study has demonstrated that linear optics offers an affordable and effective platform for implementing moderate-scale quantum measurements and computations," said Argonne Distinguished Fellow Valerii Vinokur.

Protecting nerve cells from losing their characteristic extensions, the dendrites, can reduce brain damage after a stroke. Neurobiologists from Heidelberg University have demonstrated this by means of research on a mouse model. The team, led by Prof. Dr Hilmar Bading in cooperation with Junior Professor Dr Daniela Mauceri, is investigating the protection of neuronal architecture to develop new approaches to treating neurodegenerative diseases. The current research findings were published in the journal "Proceedings of the National Academy of Sciences".

Brain nerve cells possess many arborised dendrites, which can make connections with other neurons. The highly complex, ramified structure of neurons is an important precondition for their ability to connect with other nerve cells, in order to enable the brain to function normally. In earlier studies, the Heidelberg researchers identified the signal molecule VEGFD - Vascular Endothelial Growth Factor D - as a central regulator for maintaining and restoring neuronal structures. "Our current research results demonstrate that a stroke as a consequence of an interruption of the blood supply to the brain leads to a reduction of VEGFD levels. That causes the nerve cells to lose part of their dendrites. They shrink and this leads to impairments of the cognitive and motor abilities," explains Prof. Bading.

Based on these findings, the researchers at the Interdisciplinary Centre for Neurosciences explored the question of whether the reduction of neuronal structures after a stroke can be prevented by restoring the VEGFD levels. To that effect, they applied recombinant VEGFD - produced using biotechnological methods - to the brains of mice that had suffered a stroke. "The treatment successfully preserved the dendritic arborisation and, what is important, brain damage was reduced. Furthermore, the motor abilities recovered more quickly," says Prof. Mauceri. In a second step, the researchers administered a modified form of VEGFD as nose drops, in order to simplify the treatment. They achieved the same results with this peptide mimetic, i.e. a simplified but biologically still effective version of VEGFD, which was developed in cooperation with Prof. Dr Christian Klein from Heidelberg University's Institute of Pharmacy and Molecular Biotechnology.

The scientists hope that their research findings to protect the neuronal architecture will lead to new approaches to treating stroke in the long run. "The principle of nasal delivery, in particular, would be a safe and simple form of intervention," says Prof. Bading. The Heidelberg scientists are now working on expanding the treatment trialled in the mouse model with a view to a possible clinical application.

Sometimes toxins, such as hazardous wastes and industrial byproducts, seep into groundwater, the source of our drinking water. One such pollutant is perchlorate, a chemical compound used in rocket fuels, fireworks, fertilizers and other materials. The compound is thought to contribute to health issues in humans such as hypothyroidism, the decreased production of hormones from the thyroid gland, which can impact development.

In a new study published May 25, 2020, in the journal Nature Structural & Molecular Biology, researchers at Johns Hopkins Medicine, Vanderbilt University and the University of California, Irvine, report on the mechanism that perchlorate uses to impact and damage normal functioning of the thyroid gland.

The findings, they say, suggest that an acceptable safe concentration of perchlorate in drinking water is 10 times less than previously thought.

The researchers focused on how perchlorate blocks a main route by which iodide, the negatively charged form of the element iodine, enters thyroid cells. Iodide helps the thyroid make hormones that are essential to the body's regulation of metabolism, temperature and other important functions.

Thyroid cells control the incoming flow of iodide by using a protein channel called the sodium/iodide symporter, also known as the Na+/I- symporter or NIS. Like other cellular transport systems, a "lock-and-key" approach is used to move iodide, with NIS acting as the lock and sodium as the key. Sodium fits into NIS at two binding sites to unlock the channel, enabling iodide to pass through and accumulate inside a thyroid cell.

The team, led by L Mario Amzel, Ph.D., professor of biophysics and biophysical chemistry at the Johns Hopkins University School of Medicine, and Vanderbilt University researcher Nancy Carrasco, M.D., determined that perchlorate blocks the channel by latching onto the NIS protein and changing its shape. Less sodium binds to the misshaped channel, thereby significantly lowering the amount of iodide that can be moved inside thyroid cells.

The researchers studied how varying concentrations of perchlorate affects iodide transport by first growing thyroid cells that expressed the gene SLC5A5, which encodes the instructions for building NIS channels. Next, perchlorate and radioactive iodine were placed outside of some of the cells and just radioactive iodine outside the others. Finally, the researchers tracked how much glowing iodide was allowed to enter the cells in both groups. They found that there was much less iodide inside thyroid cells treated with perchlorate than in untreated ones, even at very low concentrations of the chemical.

In May 2020, the U.S. Environmental Protection Agency (EPA) ruled not to place regulations on the amount of perchlorate that can be allowed in drinking water. The findings from the new study strongly suggest that this environmental pollutant is more hazardous than previously thought, raising serious concern about the decision.

"We hope that these findings will prompt the EPA to change its mind," Amzel says.

People respond very differently to infection with the novel coronavirus (SARS-CoV-2). While some patients develop no symptoms at all, others will develop severe disease and may even die. For this reason, there is an urgent need for 'biomarkers', quantifiable biological characteristics which could provide a reliable means of predicting disease progression and severity. A research team led by Prof. Dr. Markus Ralser (Director of Charité's Institute of Biochemistry, holder of an Einstein Professorship and Group Leader at the Francis Crick Institute) used state-of-the-art analytical techniques to rapidly determine the levels of various proteins in the blood plasma. This approach enabled the researchers to identify various protein biomarkers in the blood plasma of patients with COVID-19 which were linked to the severity of their disease.

The researchers developed a precise, high-throughput mass spectrometry platform capable of analyzing the patients' proteomes - the compendium of proteins found in biological material - at a rate of 180 samples per day. Using this technology, the team analyzed blood plasma samples from 31 men and women who were receiving treatment at Charité for COVID-19 of varying degrees of severity. The researchers were able to identify 27 proteins in the blood which varied in quantity depending on disease severity. The researchers then validated these molecular signatures by analyzing samples from another group of 17 COVID-19 patients and 15 healthy people. Protein expression signatures were able to precisely classify patients according to the World Health Organization's coding criteria for COVID-19.

"These results lay the foundations for two very different applications. One possible future use would be for disease prognosis," explains Prof. Ralser, who is also group leader at the Francis Crick Institute in London. "An early blood test would enable the treating physician to predict whether or not a patient with COVID-19 will develop severe symptoms. This could potentially save lives: the sooner physicians know which patients will require intensive care, the faster they can make use of the available treatment options." In order to get closer to this goal, the researchers will now study how the biomarker signatures change over the course of the disease.

"Another possible future use would be as an in-hospital diagnostic test, which could provide clarity regarding a patient's condition - regardless of how they themselves describe it," explains the biochemist. He adds: "In some cases, a patient's symptoms do not appear to provide an accurate picture of their true health status. An objective evaluation, based on their biomarker profile, could be extremely valuable in this regard." The research team now plan to test their new method in a larger number of patients in the hope of getting closer to developing a diagnostic test.

*Messner CB et al. Ultra-high-throughput clinical proteomics reveals classifiers of COVID-19 infection. Cell Systems (2020), doi: 10.1016/j-cels.2020.05.012.

Changes in the protein profile

Some of the 27 proteins which were found to predict the severity of COVID-19 had not previously been linked to an immune response. However, the biomarkers identified by the researchers also included clotting factors and regulators of inflammation. Some of these proteins act on interleukin 6 (IL-6) at the molecular level. IL-6 is a protein which is known to cause inflammation, and which, according to preliminary studies, is associated with severe COVID-19 symptoms. A number of the biomarkers identified as part of this study might therefore be suitable targets for treatment.

Researchers have used an unmanned aerial system (or drone) to gather data on schooling juvenile Atlantic bluefin tuna in the Gulf of Maine.

This pilot study tested whether a drone could keep up with the tuna while also taking photographs that captured physical details of this fast-moving fish. The drone was equipped with a high-resolution digital still image camera. Results show that drones can capture images of both individual fish and schools. They may be a useful tool for remotely monitoring behavior and body conditions of the elusive fish.

Individual fish lengths and widths, and the distance between fish near the sea surface, were measured to less than a centimeter of precision. We used an APH-22, a battery-powered, six-rotor drone. The pilot study was conducted in the Atlantic bluefin tuna's foraging grounds northeast of Cape Cod in the southern Gulf of Maine.

"Multi-rotor unmanned aerial systems won't replace shipboard surveys or the reliance on manned aircraft to cover a large area," said Mike Jech, an acoustics researcher at the Northeast Fisheries Science Center in Woods Hole, Massachusetts and lead author of the study. "They have a limited flight range due to battery power and can only collect data in bursts. Despite some limitations, they will be invaluable for collecting remote high-resolution images that can provide data at the accuracy and precision needed by managers for growth and ecosystem models of Atlantic bluefin tuna."

Results from the APH-22 study were published in March 2020 in the Journal of Unmanned Vehicle Systems. Researchers conducted their work in 2015. They then compared their study results to values in published data collected in the same general area. They also compared it to recreational landings data collected through NOAA Fisheries' Marine Recreational Information Program.

Atlantic bluefin tuna is a commercially and ecologically important fish. The population size in the western Atlantic Ocean is unknown. Fishery managers need biological data about this population, but it is hard to get. Highly migratory species like Atlantic bluefin tuna often move faster than the vessels trying to sample them. The tuna are distributed across large areas, and can be found from the sea surface to hundreds of feet deep.

Sampling with traditional gear -- nets and trawls -- is ineffective. Acoustical methods are useful but limited to sampling directly below a seagoing vessel with echosounders or within range of horizontal sonar.

It is also difficult to estimate the number of tuna in a school from an airplane. Both fish availability and perception biases introduced by observers can affect results. Estimates of abundance and size of individuals within a school are hard to independently verify.

Taking precision measurements of animals that are in constant motion near the surface proved easier with a drone that is lightweight, portable, and agile in flight. It can carry a high-quality digital still camera, and be deployed quickly from a small fishing boat.

Short flight times limit a drone's ability to survey large areas. However, they can provide two-dimensional images of the shape of a fish school and data to count specific individuals just below the ocean surface.

The APH-22 system has been tested and evaluated for measuring other marine animals. It's been used in a number of environments -- from Antarctica to the Pacific Ocean -- prior to its use in the northwest Atlantic Ocean. Previous studies estimated the abundance and size of penguins and leopard seals, and the size and identity of individual killer whales.

"The platform is ideal for accurately measuring fish length, width, and the distance between individuals in a school when you apply calibration settings and performance measures," Jech said. "We were able to locate the hexacopter in three-dimensional space and monitor its orientation to obtain images with a resolution that allowed us to make measurements of individual fish."

As new unmanned aerial systems are developed, their use to remotely survey Atlantic bluefin tuna and other animals at the sea surface will evolve. It may minimize the reliance on manned aircraft or supplement shipboard surveys.

The International Commission for the Conservation of Atlantic Tunas governs tuna fishing. It is entrusted to monitor and manage tuna and tuna-like species in the Atlantic Ocean and adjacent seas. NOAA Fisheries manages the Atlantic bluefin tuna fishery in the United States and sets regulations for the U.S. fishery based on conservation and management recommendations from the international commission.

An indoor residual spray made by combining a type of volcanic glass with water showed effective control of mosquitoes that carry malaria, according to a new study. The findings could be useful in reducing disease-carrying mosquito populations - and the risk of malaria - in Africa.

Malaria, an infectious disease transmitted by mosquitoes, annually kills some 400,000 people in Africa. The use of insecticide-treated bed nets and indoor residual sprays are the most common and effective methods of reducing mosquito populations in Africa. But mosquitoes are becoming increasingly resistant to the commonly used insecticides such as pyrethroids, so the need for alternative safe chemistry to use in controlling mosquitoes is important.

The volcanic glass material used in this new intervention is perlite, an industrial mineral most frequently used in building materials and in gardens as a soil additive. The tested insecticide created from perlite, called Imergard WP, can be applied to interior walls and ceilings - and perhaps even inside roofs - as an indoor residual spray. The spray contains no additional chemicals, is not toxic to mammals and will be cost effective. Early results show that mosquitoes do not appear to have resistance to the perlite spray.

In the study, North Carolina State University entomologists worked with the Innovative Vector Control Consortium (IVCC) based at the Liverpool School of Tropical Medicine and Imerys Filtration Minerals Inc. to test Imergard WP. Researchers used the spray in experimental huts in the Republic of Benin (West Africa) to test the effects of the spray on both wild and more susceptible strains of Anopheles gambiae mosquitoes, the primary malaria vector in sub-Saharan Africa.

Researchers used four different tests to verify the efficacy of Imergard WP. Control study huts had no mosquito-prevention spray. In the second group hut walls were coated with a common pyrethroid. Hut walls were sprayed with Imergard WP in the third group, while in the fourth group hut walls were sprayed with a mixture of Imergard WP and the common pyrethroid.

Huts with walls treated with Imergard WP, with and without the pyrethroid, showed the largest mosquito mortality rates. Results showed mortality rates of mosquitos alighting on Imergard WP-treated walls were greater than 80% up to five months after treatments, and 78% at six months. The treatments were effective against both susceptible and wild-type mosquitoes.

"The statically transferred perlite particles essentially dehydrate the mosquito," said Mike Roe, William Neal Reynolds Distinguished Professor of Entomology at NC State and the corresponding author of the paper. "Many die within a few hours of contact with the treated surface. Mosquitoes are not repelled from a treated surface because there is no olfactory mechanism to smell rock."

Huts sprayed with only the common pesticide had mosquito mortality rates of around 40 to 45% over five months, with those rates dropping to 25% in month six of the study.

"The processing of perlite as an insecticide is novel," said David Stewart, commercial development manager for Imerys, the company that created Imergard WP, and co-author of the paper. "This material is not a silver bullet but a new tool that can be considered as part of an insect vector management program."