Culture

Animal acoustic signals are amazingly diverse. Researchers from the University of Zurich and the University of Saint-Etienne, together with French, American and Dutch collaborators, explored the function and diversification of animal acoustic signals and the mechanisms underlying the evolution of animal communication systems.

To this end, they used Shannon & Weaver's 'Mathematical Theory of Communication' originally ap-plied to telecommunications in 1949, which has transformed the scientific understanding of animal communication. This theory allows the amount of information in a signal to be quantified. The researchers were the first to use this framework within an evolutionary perspective to explore the bio-logical information encoded in an animal signal.

How drumming structure evolves over time

In deciding which biological model to choose, the researchers selected the woodpeckers' drumming as their ideal candidate. This bird family is known for rapidly striking their beaks on tree trunks to communicate. The team combined acoustic analyses of drumming from 92 species of woodpeckers, together with theoretic calculations, evolutionary reconstructions, investigations at the level of ecolog-ical communities as well as playback experiments in the field.

"We wanted to test whether drumming has evolved to enhance species-specific biological information, thereby promoting species recognition", says lead author Maxime Garcia of the UZH Department of Evolutionary Biology and Environmental Studies.

Constant amount of information for 22 million years

Results demonstrate the emergence of new drumming types during woodpeckers evolution. Yet, despite these changes in drumming structure, the amount of biological information about species identity has remained relatively constant for 22 million years. Selection towards increased biological infor-mation thus does not seem to represent a major evolutionary driver in this animal communication system. How then can biological information be concretely maintained in nature? Analyses of existing communities around the globe show that ecological arrangements facilitate the efficiency of drumming signals: Communities are composed of only a few species, which distribute their drumming strategies to avoid acoustic overlap. "The responses to different drumming structures seen in our experimental approach show the ability of individuals to recognize their own species based on acoustic cues about species identity found in drumming signals", says Garcia. This way, biological information about spe-cies identity can be maintained without necessarily inducing a strong evolutionary pressure on drum-ming signals.

The present study shows that random and unpredictable changes in the structure of communication signals over time can occur while maintaining the signals overall informative potential within and across species. This work leads the way to further investigate the evolution of meaning associated with communicating through multiple communication channels.

In the search for the chemical origins of life, researchers have found a possible alternative path for the emergence of the characteristic DNA pattern: According to the experiments, the characteristic DNA base pairs can form by dry heating, without water or other solvents. The team led by Ivan Halasz from the Rudjer Boskovic Institute and Ernest Mestrovic from the pharmaceutical company Xellia presents its observations from DESY's X-ray source PETRA III in the journal Chemical Communications.

"One of the most intriguing questions in the search for the origin of life is how the chemical selection occurred and how the first biomolecules formed," says Tomislav Stolar from the Rudjer Boskovic Institute in Zagreb, the first author on the paper. While living cells control the production of biomolecules with their sophisticated machinery, the first molecular and supramolecular building blocks of life were likely created by pure chemistry and without enzyme catalysis. For their study, the scientists investigated the formation of nucleobase pairs that act as molecular recognition units in the Deoxyribonucleic Acid (DNA).

Our genetic code is stored in the DNA as a specific sequence spelled by the nucleobases adenine (A), cytosine (C), guanine (G) and thymine (T). The code is arranged in two long, complementary strands wound in a double-helix structure. In the strands, each nucleobase pairs with a complementary partner in the other strand: adenine with thymine and cytosine with guanine.

"Only specific pairing combinations occur in the DNA, but when nucleobases are isolated they do not like to bind to each other at all. So why did nature choose these base pairs?" says Stolar. Investigations of pairing of nucleobases surged after the discovery of the DNA double helix structure by James Watson and Francis Crick in 1953. However, it was quite surprising that there has been little success in achieving specific nucleobase pairing in conditions that could be considered as prebiotically plausible.

"We have explored a different path," reports co-author Martin Etter from DESY. "We have tried to find out whether the base pairs can be generated by mechanical energy or simply by heating." To this end, the team studied methylated nucleobases. Having a methyl group (-CH3) attached to the respective nucleobases in principle allows them to form hydrogen bonds at the Watson-Crick side of the molecule. Methylated nucleobases occur naturally in many living organisms where they fulfil a variety of biological functions.

In the lab, the scientists tried to produce nucleobase pairs by grinding. Powders of two nucleobases were loaded into a milling jar along with steel balls, which served as the grinding media, while the jars were shaken in a controlled manner. The experiment produced A:T pairs which had also been observed by other scientists before. Grinding however, could not achieve formation of G:C pairs.

In a second step, the researchers heated the ground cytosine and guanine powders. "At about 200 degrees Celsius, we could indeed observe the formation of cytosine-guanine pairs," reports Stolar. In order to test whether the bases only form the known pairs under thermal conditions, the team repeated the experiments with mixtures of three and four nucleobases at the P02.1 measuring station of DESY's X-ray source PETRA III. Here, the detailed crystal structure of the mixtures could be monitored during heating and formation of new phases could be observed.

"At about 100 degrees Celsius, we were able to observe the formation of the adenine-thymine pairs, and at about 200 degrees Celsius the formation of Watson-Crick pairs of guanine and cytosine," says Etter, head of the measuring station. "Any other base pair did not form even when heated further until melting." This proves that the thermal reaction of nucleobase pairing has the same selectivity as in the DNA.

"Our results show a possible alternative route as to how the molecular recognition patterns that we observe in the DNA could have been formed," adds Stolar. "The conditions of the experiment are plausible for the young Earth that was a hot, seething cauldron with volcanoes, earthquakes, meteorite impacts and all sorts of other events. Our results open up many new paths in the search for the chemical origins of life." The team plans to investigate this route further with follow-up experiments at P02.1.

DESY is one of the world's leading particle accelerator centres and investigates the structure and function of matter - from the interaction of tiny elementary particles and the behaviour of novel nanomaterials and vital biomolecules to the great mysteries of the universe. The particle accelerators and detectors that DESY develops and builds at its locations in Hamburg and Zeuthen are unique research tools. They generate the most intense X-ray radiation in the world, accelerate particles to record energies and open up new windows onto the universe. DESY is a member of the Helmholtz Association, Germany's largest scientific association, and receives its funding from the German Federal Ministry of Education and Research (BMBF) (90 per cent) and the German federal states of Hamburg and Brandenburg (10 per cent).

Could a poo transplant one day be the secret of eternal youth?

Faecal transplants could one day be used as a therapy to restore cognitive function in the elderly - according to new research from the University of East Anglia, the University of Florence and the Quadram Institute.

A new study published today shows how faecal transplants from older to younger mice altered their gut microbiome, which in turn impacted their spatial learning and memory.

The research team hope that reversing the procedure could one day see faecal transplantation used to combat cognitive decline among the elderly.

Dr David Vauzour, from UEA's Norwich Medical School, said: "Ageing is an inevitable process that starts immediately after birth and ultimately leads to physical health problems as well as a decline in psychological well-being and cognitive function.

"Research has shown that the aging process may be linked with age-related changes in our gut microbiota.

"Recently, the existence of two-way communication between the gut and the brain - known as the 'gut-brain axis' - has emerged as an important player in shaping aspects of behaviour and cognitive function.

"We wanted to see whether transferring gut microbes from older to younger mice could affect parts of the central nervous system associated with ageing."

The research team performed faecal transplants from older adult mice to younger adult mice and then assessed the young adults for markers such as anxiety, exploratory behaviour and memory.

After the transplantation, the team found significant differences in the young mice's microbial profiles.

While the young adults showed no significant changes in markers of anxiety, explorative behaviour or locomotor activity, they did show impaired spatial learning and memory as measured in a maze test.

These changes were paralleled by alterations in the expression of proteins associated with synaptic plasticity and neuro transmission, and changes to cells in the hippocampus part of their brains - responsible for learning and memory.

Dr Vauzour said: "Our research shows that a faecal transplantation from an old donor to a young recipient causes an age-associated shift in the composition of gut microbiota.

"The procedure had an impact on the expression of proteins involved in key functions of the hippocampus - an important part of the brain that has a vital role in a variety of functions including memory, learning but also in spatial navigation and emotional behaviour and mood.

"In short, the young mice began to behave like older mice, in terms of their cognitive function."

Prof Claudio Nicoletti, from the University of Florence, Italy, said: "While it remains to be seen whether transplantation from very young donors can restore cognitive function in aged recipients, the findings demonstrate that age-related shifts in the gut microbiome can alter components of the central nervous system.

"This work highlights the importance of the gut-brain axis in ageing and provides a strong rationale to devise therapies aiming to restore a young-like microbiota to improve cognitive functions and quality of life in the elderly," he added.

"Manipulating the microbiome is increasingly being seen as a way of improving or maintaining human health, and these results are an exciting indication of its potential for helping us age healthily" said Prof Arjan Narbad from the Quadram Institute.

"We have established an FMT service on the Norwich Research Park to treat serious gut infections and now want to explore in humans its effectiveness in combating a number of age-related conditions, including cognitive decline."

The research was led by a team at UEA and the University of Florence, in collaboration with colleagues at the University of Milan, the Earlham Institute, University of Siena, the Quadram Institute, and Nottingham Trent University.

The study was based on the authors' original hypothesis that a specific novel mechanism responsible for linking distinct symptoms into a single disease may exist in the brain. 'A disease is more complex than a collection of symptoms. For example, while decreased appetite or blues can occur in many people, only together these symptoms form a disease - depression. We suggested that there must be some kind of molecular "link", likely mediated by specific brain genes, that "bring together" diseases by combining their symptoms, but not causing symptoms per se,' explained Professor Alan Kaluev, study's Principal Investigator and head of the Laboratory of Biological Psychiatry at the Institute of Translational Biomedicine at St Petersburg University.

When studying mental disorders, researchers try to understand which gene in the brain is responsible for a particular symptom. The C57BL/6?J mice in a chronic social stress model are often used as an experimental model. This animal model, created in the 1980s in Novosibirsk, is generated by placing two male mice in the same cage, where they begin to fight, after which they are separated by a transparent partition with holes through which they can feel each other, but cannot contact. They are left separated in the same cage for the whole day, and then the manipulations are repeated daily for 3 weeks. As a result, the 'winners' and the 'losers' reveal themselves clearly, and the state of 'losers' is of particular interest for studying anxiety and depression.

'In the classical model of chronic social stress, if the defeated losers are stressed for about 10 days, they develop anxiety-like state, but do not show 'depression' yet. However, if you continue to stress them, then after 20 days these animals develop a pronounced depressive-like state, but no longer have anxiety. Simply put - it takes 10 days of fights to cause "mouse" anxiety - one brain pathology. And by 20 days they already have depression. Thus, the question we asked in the present study concerned what happens in the middle of this interval - for example, on day 15? Hypothetically, this is the point where one pathology (anxiety) begins to turn into another (depression). If you imagine a train at a junction: it can go left or right - then the track switches, and the switch (relay) is the 15th day. This "relay" itself does not cause anxiety or depression. However, this switch in the brain may involve its own set of unique genes,' explained Professor Kaluev.

As he noted, these 'switch' genes cannot be detected by classical methods of genetics, because they are not responsible for any symptom: neither for anxiety, nor for depression. They only hypothetically 'switch' from one pathology to another. To experimentally prove their hypothesis, the researchers performed a genome-wide screening of mice brain gene activity in two key areas - the prefrontal cortex (responsible for long-term planning and social behaviour) and the hippocampus (responsible for memory).

'Our present discovery can be briefly summarized as follows: we found that on Day 15 during the transition from experimental anxiety- to depression-like state in mice, neither genes associated with neurotransmitters (as during the anxiety-like state) nor with the inflammation (as with depression-like state) are involved. Rather, these 'transitional' mechanisms are associated with the cytoskeleton and astrocytes - the glial cells in the brain that are increasingly associated with mental illness. Overall, we showed that when in mice one brain pathology progresses into another, unique cellular mechanisms are activated. In fact, they may act as a unique molecular "switch" that can send the vector of pathogenesis either in one direction (anxiety) or in another (depression),' explained Dr. Kaluev.

The scientist also noted that with continued stress, in about 70% of people with chronic anxiety it can turn into depression. At the same time, traditional antidepressants do not always work effectively. According to study director, only about 30-40% of people respond to therapy, and the majority either does not respond at all, or reacts in a weak form. He stressed that, at the same time, the number of detected cases is growing every year, and fundamentally new drugs for depression have not appeared over the past half century.

'It therefore seems that stopping depression is a key unmet biomedical task. And since existing antidepressants are not always effective, the question arises: how can we stop this 'rushing train' of brain affective pathology? If it is already on the path to depression, can we slow it down? Or, alternatively, we can target the "switch" of the track instead, to present depression progression? As such, the putative mechanisms we have discovered can become a new target for creating fundamentally new classes of psychotropic drugs,' added the professor.

He also emphasised that our mouse data are highly consistent with recent clinical evidence where astrocytes and cytoskeletal mechanisms are increasingly implicated in human affective pathogenesis. The research team plans to test their hypothesis in humans, in the long term aiming to understand how exactly to influence the 'switch' and stop depressive disorder at its very beginning.

We need to know about these psychological and social profiles so we can understand how protective actions against contagious diseases are adopted, and then define the correct preventive approaches. At the very start of the coronavirus crisis - before restrictive measures were taken - a team of health behaviour specialists from the University of Geneva (UNIGE) managed to collect a large amount of data about the adoption of protective measures. Through a study published in the journal Applied Psychology: Health and Well-Being, the Geneva psychologists analysed how people in Britain followed the precautions recommended in their country. The study focuses on how the behaviour of others influences individual decision-making, known as the social dilemma. It notes that beliefs about COVID-19, such as thinking that the disease is dangerous or feelings of vulnerability, have little impact on whether or not an individual takes up protective measures. The people least likely to adopt these measures are those who believe that the precautions taken by others mean that they do not need to take their own. These psychosocial profiles (among others identified in the study) point to possible solutions for creating prevention messages that are more effective.

A better understanding of human behaviour when it comes to making a positive contribution to a community can be used to develop more appropriate prevention measures and messaging. This is a form of behaviour analysis that is very useful for ecological issues and blood donation. Lisa Moussaoui is first author of the study as well as being a lecturer and research fellow in the health psychology research group in UNIGE's Faculty of Psychology and Educational Sciences (FPSE). She explains the approach thus: &laquoWe are trying to understand how people make decisions and act so that preventive interventions can be made.» This is why, when the Swiss Federal Office of Public Health announced it would be introducing a semi-lockdown on March 13, 2020, the researcher and her colleagues decided to bring their expertise to bear regarding the COVID-19 health crisis.

Using the United Kingdom as a model

The Geneva psychologists turned to the United Kingdom, which - unlike Switzerland - had not yet entered lockdown: this meant the researchers could analyse behaviours before the official measures came into force, enabling them to concentrate on the initial decisive phases. A representative sample of 1,006 UK citizens served as the basis for the study, which included a series of questions relating to monitoring the adoption of the preventive measures recommended by the British health authorities. &laquoWe measured variables such as perceived vulnerability to COVID-19, the perceived severity of the disease and a number of other beliefs,» says Nana Ofosu, a doctoral student at UNIGE and co-author of the study.

Few socio-demographic differences

The psychologists observed that preventive measures were spontaneously adopted by a large section of the population. &laquoIt's a known phenomenon. Informing people about the presence of a danger is enough to bring about a massive and rapid change in behaviour. We've seen the same thing in other tragic situations, such as the AIDS pandemic. But, in spite of everything, pockets of resistance do exist,» explains Olivier Desrichard, FPSE professor and co-author of the study.

Level of education, family environment, age and the number of cases declared in the region do not influence behaviour. &laquoIt's an outcome that contradicts rumours claiming that certain categories of the population, such as young people, followed instructions less than others,» adds Moussaoui.

How other people behave: a source of social dilemma

&laquoIf no one else is doing it, why should I be the only one making the effort? &laquo The more the study participants agreed with this question, the less they adopted preventive measures. Another factor negatively influences their adoption: the &laquodrop-in-the-bucket» phenomenon - the feeling that your own contribution is pointless compared to the size of the danger. Finally, the study emphasises the fact that the more social contacts the participants had, such as professional relationships, the more they felt vulnerable, even though this did not inspire them to adopt the correct actions.

Preventive approach that needs refining

The study confirms the fact that social dilemmas influence behaviour. This psychosocial approach offers an interesting counterpoint to the way information is communicated about COVID-19, one that focuses on the dangerous nature of the virus and the importance of observing instructions. &laquoIt's important to know the real determinants of behaviour before embarking on a preventive action so as not to miss the intended goal. Most of the people interviewed were already convinced about the importance of respecting the recommendations. It follows,» concludes Moussaoui,» that this kind of message is not really useful to influence their behaviour».

What The Study Did: The U.S. Army Public Health COVID-19 Task Force describes the results of an independent investigation of the shore-based USS Theodore Roosevelt outbreak response and 736 sailors in isolation status.

Authors: Gadiel R. Alvarado, D.O., of the Brooke Army Medical Center in Fort Sam Houston, Texas, 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/jamanetworkopen.2020.20981)

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

DUARTE, Calif. -- A City of Hope-led study revealed little effort has been made to improve older adult representation in clinical trials of new cancer drugs, even when the treatment is aimed at a disease that disproportionately affects this age group.

"There is currently no incentive to establish real-world effectiveness among older adults. Older adults need a seat at the table," said Mina Sedrak, M.D., M.S., lead author of the study and deputy director of the Center for Cancer and Aging at City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases.

Two in 5 Americans with cancer are age 70 or older, yet fewer than 25% of patients in cancer clinical trials registered with the Food and Drug Administration are in this age group, Sedrak said.

The study was published in the journal CA: A Cancer Journal for Clinicians on Oct. 1. Researchers reviewed 8,691 studies that evaluated barriers which hindered older adults from participating in cancer trials. Twelve articles defined complex, interrelated problems as root causes, including stringent eligibility criteria, physician concern for toxicity, ageism, transportation and caregiver burden.

Only one study implemented an intervention meant to increase enrollment of older adults in trials - and it was not successful. This finding starkly amplifies the lack of effective strategies to improve participation of this underrepresented group in cancer research.

The researchers report that cancer trials must ask appropriate questions tailored or driven by the needs of older adults with cancer and should measure relevant outcomes. Their call to action applies to all oncologists and primary care providers, not just geriatric oncologists, Sedrak said, adding that patients should advocate for themselves.

"Ask your doctor about clinical trial opportunities when you're diagnosed with cancer and do your own research because there may be an option that you haven't heard about. It may benefit you, but perhaps your doctor may not have considered you for the investigational trial," he said.

What The Study Did: This observational study looked at the association between Medicaid expansion under the Patient Protection and Affordable Care Act (ACA) and long-term home health care and nursing home use among newly eligible low-income adults and older adults whose eligibility did not change.

Authors: Courtney Harold Van Houtven, Ph.D., of the Durham Veterans Affairs Health Care System in Durham, North Carolina, 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/jamanetworkopen.2020.18728)

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

Benign breast diseases (BBD), which are non-cancerous disorders of the breast, such as lumps, are known to increase the chances of subsequent breast cancer. Now a team of Spanish researchers have found that the way BBD is detected as part of a national screening programme is an indication of which are more likely to become cancerous.

The findings from a team led by Professor Xavier Castells, head of the epidemiology department at the Hospital del Mar Medical Research Institute, Barcelona, Spain, will be presented at the 12th European Breast Cancer Conference on Saturday.

BBD detected on the first occasion a woman attends for breast screening (usually at the age of 50 in Spain and many other European countries with national screening programmes) is classified as "prevalent" BBD, whereas those detected on subsequent visits, which occur every two years in Spain, are classified as "incident" BBD.

Dr Marta Román, a senior researcher in the epidemiology department at the Hospital del Mar Medical Research Institute, told the conference: "Our results show that women with a benign breast disease diagnosed from the second screening onwards have a significantly higher subsequent risk of breast cancer than those with a BBD diagnosed on their first mammographic screening."

The researchers analysed data from 629,087 women who underwent 2,327,384 screening mammograms between 1995 and 2015, and they followed them until 2017. They found that women diagnosed with incident BBD had a 2.67-fold increased chance of developing breast cancer than women with no BBD, while women with prevalent BBD had a 1.87-fold increased risk.

They also classified the BBDs as non-proliferative or proliferative, depending on whether or not the breast tissue showed an increase in the growth of certain cells, such as the ductal cells found in ductal hyperplasia in which there is an overgrowth of cells lining the ducts inside the breast.

They found that women with proliferative BBD had a 3.28-fold increased chance of breast cancer compared to women with no breast disease, while women with non-proliferative BBD had a 1.96-fold increased risk.

Dr Román said: "We found the highest risk of breast cancer in women with incident, proliferative BBD. They had a nearly four-fold increased risk of breast cancer compared to women with no BBD."

Women with an incident, non-proliferative BBD had a 2.39-fold increased chance of subsequently developing breast cancer compared to women with no BBD; women with prevalent, proliferative BBD had a 2.85-fold increased risk; and women with prevalent, non-proliferative BBD had a 1.63-fold increased risk.

The researchers hope that their findings will be useful in designing personalised breast cancer screening strategies in order to improve the effectiveness of breast cancer screening.

"The likelihood that a woman will benefit from screening mammography depends on her risk for developing clinically significant breast cancer in her lifetime," said Dr Román. "Taking individual risk factors beyond age into account should enable the classification of women into groups at varying risk of breast cancer. Personalised risk-based screening going beyond the current 'one-size fits all' recommendation may increase the effectiveness of breast cancer screening. Including information from BBD, in addition to other factors, to develop risk-based screening approaches can help with the prediction of whether a woman would develop breast cancer in a defined period.

"Different screening strategies can be considered for each woman based on her personal risk of breast cancer: by modifying the screening interval, which could be annual, or every two or three years, the method of screening, for instance, mammogram, ultrasound or magnetic resonance imaging, or the age range in which the woman is invited for screening participation."

Dr Román and her colleagues believe these findings will help clinicians to understand the different risks associated with BBD and to improve the accuracy of breast cancer risk predictions.

In a statement before the conference, Professor Xavier Castells said: "Clinicians involved in the management of women with BBDs could offer targeted surveillance strategies considering, in addition to other factors, if the BBD was found at first or in subsequent screening examinations. Also, this information will be included in an individualised model that can be used to predict an individual woman's risk of developing breast cancer in five or ten years' time. We have tested this in the context of a screening programme, which also includes information on breast density, age, family history of breast cancer and mammographic features."

The team is part of MyPebs: an international randomised controlled trial, funded by the European Union that investigates whether a risk-based breast cancer screening strategy, based on a clinical risk score, is more effective than standard screening. This international project, which started in July 2019, will recruit 90,000 participants from six countries [1] and follow them for four years.

Co-chair of EBCC12, Professor Javier Cortes, is clinical investigator of the breast cancer research programme at Vall d'Hebron Institute of Oncology, Barcelona, and head of the breast cancer programme at the IOB Institute of Oncology, Madrid and Barcelona, and was not involved with this research. He commented: "We know that population-based breast cancer screening programmes save lives by detecting cancer at an early stage. However, it can raise questions about not only the best way of treating women with cancer that may never become a problem in their lifetimes, but also what to do about women with benign breast disease.

"No patient wants to have screening mammograms more often than is needed, but patients and clinicians want to be sure that if benign breast disease does develop into cancer, it can be detected quickly. The results from this study provide us with useful information that can improve the accuracy of breast cancer risk prediction models so that we can tailor surveillance strategies for patients with this disease."

(ends)

Abstract no: 15, "Differences in breast cancer risk after a benign breast disease according to the screening type", Proffered papers session: "Are your breasts still at risk?", Saturday, 16.00-16.45 hrs, Channel 3 (Dr Román's presentation will be at 16.10 hrs).
[1] The countries taking part in the MyPebs trial are: France, Belgium, Israel, Italy, the UK and Spain.

Four out of five people experiencing the recent loss of smell and/or taste tested positive for COVID-19 antibodies--and of those who tested positive, 40 percent did not have cough or fever, reports a new study in PLOS Medicine by Prof. Rachel Batterham at University College London and colleagues.

COVID-19 can cause loss of taste and smell, but the prevalence of COVID-19 antibodies in people reporting these symptoms is unknown, and the significance of loss of smell and/or taste as a predictor of COVID-19 is not well understood. To estimate the seroprevalence of SARS-CoV-2 antibodies in people with acute loss of their sense of smell and/or taste, researchers enrolled 590 people self-reporting a loss of taste/smell in the previous month. Following verification of symptoms via a telemedicine consultation, 567 participants with smell and/or taste loss participants underwent a SARS-CoV-2 antibodies test.

78% had SARS-CoV-2 antibodies, and participants with loss of smell were almost 3 times more likely to have SARS-CoV-2 antibodies compared to those with loss of taste, suggesting that a loss of smell is a highly specific symptom of COVID-19. Of the 78% of participants testing positive for antibodies, 40% had neither cough nor fever. While the study had limitations, such as the self-reporting of smell/taste changes and the lack of a control group, the researchers believe the evidence indicates that loss of smell should be taken into greater consideration in COVID-19 public health measures such as testing, case isolation, and treatment strategies.

These findings also have significant implications for policy makers globally, as most countries do not recommend self-isolation and testing based on acute loss of smell/taste. This study suggests that an over-reliance on cough and fever as the main symptoms of COVID-19 may be flawed and that loss of smell needs to be urgently recognized globally as a key symptom of COVID-19.

Prof. Rachel Batterham, who led the study, said "Early self-recognition of COVID-19 symptoms by the members of the public, together with rapid self-isolation and PCR testing are vital in order to limit spread of the disease. Currently, most countries around the world do not recognize sudden loss of smell as a symptom of COVID-19.

78% of participants in our community-based study with sudden onset loss of smell or taste had SARS-CoV-2 antibodies. The vast majority had mild symptoms and 40% did not report having a fever or cough. Our findings suggest that people who notice a loss in their ability to smell every day house-hold odors such as garlic, coffee and perfumes should self-isolate and seek PCR testing. Loss of sense of smell needs to be recognized globally by policy makers as a key symptom of COVID-19."

The first comprehensive study of DNA changes in healthy and diseased human bladder tissue has revealed that 'cancer-driving' mutations are common in healthy bladder tissue. The study, conducted by scientists at the Wellcome Sanger Institute, the University of Cambridge and their collaborators, provides an unprecedented view of the first steps towards bladder cancer.

Published today (1 October 2020) in Science, the research uncovered high variation in the number and types of changes between individuals, indicating that a wide range of factors influence how bladder cancer develops. The researchers also provided new insights into the link between smoking and bladder cancer, whereby bladder tissue is exposed to tobacco chemicals present in urine.

More than 10,000 people are diagnosed with bladder cancer every year in the UK, with around 5,000 deaths. Around 60 per cent of new cases occur in people aged 75 and over. Around half of bladder cancer cases are estimated to be preventable. Early diagnosis is also crucial, with 95 per cent of those diagnosed early surviving for one year or more, dropping to 36 per cent for late stage diagnosis*.

Cancers occur due to changes in DNA, known as somatic mutations, which continuously occur in all of our cells throughout life. Some somatic mutations, particularly those affecting known 'cancer genes', confer a competitive advantage that allows these mutated cells to expand more rapidly than normal cells and can lead to disease.

Technological developments have enabled the detection of somatic mutations linked to cancer in normal tissues, providing insights into the earliest stages of cancer and raising the prospect of early detection and treatment strategies**.

This new study used DNA sequencing to better understand the genetic changes in healthy and diseased bladder tissue. Clinicians from the University of Cambridge provided donated bladder tissue from five people with bladder cancer and 15 people with no history of cancer.

Researchers at the Wellcome Sanger Institute then took 2,097 biopsies from the tissue samples, using a technique called laser-capture microscopy to isolate segments of just a few hundred cells. DNA from these samples was genome sequenced and the sequences were analysed to characterise the landscape of somatic mutations.

The team found an unexpectedly high variability in the number and types of mutations and in the frequency of 'cancer-driving' mutations between individuals, suggesting that a wide range of factors affect the accumulation of mutations in the bladder. Some of these factors could be identified by their 'mutational signature' - tell-tale patterns of mutation in the genome caused by a certain chemical or process.

The study identified a new mutational signature associated with smoking, shedding light on why tobacco is the single greatest risk associated with bladder cancer. Though the bladder does not come into contact with smoke directly, the chemicals in tobacco products are filtered out of the body by the kidneys and come into contact with the bladder in the urine.

Andrew Lawson, first author of the study from the Wellcome Sanger Institute, said: "One of the questions we sought to answer with this study was why bladder cancers have some of the highest mutation rates and cancer-driving mutations of any cancer type, even though the cells in the bladder divide slowly, reducing the chance of a genetic error. The high patient-to-patient variation in which genes were mutated and in the types of mutations may be consistent with the wide variety of factors that can contribute to bladder cancer. Further studies on the causes behind this variation could help uncover hidden causes of bladder cancer."

The researchers were surprised to find that mutations in key cancer genes such as TP53, FGFR3 and TERT were largely absent from healthy bladder tissue, despite the high number of mutations overall. As mutations in these genes are common in bladder tumours, their presence is a strong indicator that disease has set in.

Thomas Mitchell, a senior author of the study from Cambridge University Hospitals and the Wellcome Sanger Institute, said: "Like many cancers, early diagnosis of bladder cancer gives the patient a much greater chance of survival. The presence of mutations in key cancer genes in bladder tumours that are usually absent in normal tissue opens up the possibility of looking for these changes in fragments of DNA that are present in urine. These 'liquid biopsies' could be a non-invasive way to screen for bladder cancer earlier, which could help reduce the number of people who die from this disease."

Dr Inigo Martincorena, lead author of the study from the Wellcome Sanger Institute, said: "This study reveals an unexpectedly rich landscape of mutation and selection in normal bladder, with large differences across individuals driven to some extent by our daily exposures. Thanks to technical advances, our understanding of how our cells mutate, compete and evolve as we age have been transformed over the last few years. In addition to shedding light on the origins of cancer and informing early detection efforts, these observations raise questions about the possible role of these widespread mutations in ageing and other diseases."

The COVID-19 pandemic has created a flood of potentially substandard research amid the rush to publish, with a string of papers retracted or under a cloud and a surge in submissions to pre-print servers where fewer quality checks are made, a leading ethicist has warned in the Journal of Medical Ethics.

This has implications for patients, clinicians, and potentially government policy, says Adjunct Professor Katrina Bramstedt, Bond University, Queensland, Australia and Secretary General at Luxembourg Agency for Research Integrity.

The rapid spread of COVID-19 and its transition into a global pandemic propelled researchers to begin the search for treatments and vaccines in earnest.

Scientific and medical Journals have since been flooded with submissions, while thousands of papers, which have not undergone thorough quality checks, have been posted on preprint servers.

As of 7 May 2020, 1221 studies on COVID-19 were registered on the international clinical trial registry site, ClinicalTrials.gov.

And as of 31 July 2020, 19 published articles and 14 preprints about COVID-19 have been retracted, withdrawn, or had serious doubts raised about the integrity of their data, formally known as an expression of concern.

Most of these papers came from Asia (n=19; 57.5%), with over half coming from China (n=11; 58%).

But as the author points out: "No research team is exempt from the pressures and speed at which COVID-19 research is occurring. And this can increase the risk of honest error as well as deliberate misconduct."

The reason for the removal of the 33 papers isn't known in 3 cases, but data falsification, methodological issues, and concerns about interpretation of data and conclusions, as well as authorship and participant privacy issues were among the reasons in the other papers.

Two preprints (SSRN preprint server) and two research papers in The Lancet and New England Journal of Medicine were retracted because of unverifiable data common to all four.

And a preprint from the USA about COVID-19 antibody seroprevalence has come under scrutiny for an undisclosed conflict of interest.

There are obvious implications for the journal and the researchers involved, even if they are innocent of any research misconduct, points out the author. The evidence suggests that in such cases, the citations of prior collaborators can take a hit and fall by 8-9%.

But there are also implications for patients. "Patient harm that is significant, permanent and irreversible could result from using faulty research results from preprints as well as published papers," she says.

The rush to publish means there is less time for quality checks by researchers and their supervisors and for thorough reviews of study applications by research ethics committees, says Professor Bramstedt.

Added to which, these committees can't be expected to routinely include the key experts needed for COVID-19 research, such as immunologists, microbiologists and lung disease specialists.

Journals, too, rely on a fleet of peer reviewers, all of whom work on a voluntary basis and have competing demands on their time.

To counter these issues, the author suggests that the efficiency of the submission process is tightened up and that research ethics and integrity training be mandated for all researchers.

They should also have timely access to ethical advice on research dilemmas involving topics such as authorship disputes, image manipulation, citations and referencing, informed consent, ethical participant recruitment, etc.

Any infractions of policies and standards should have meaningful consequences to ward off repeat offences, she suggests, adding that it's important to publicise the results of any investigations, whatever the outcome.

In a personal comment, not found in the text, Professor Bramstedt emphasizes: "Research has the potential to enter the public domain and be used by many stakeholders, including governments and policy makers, so the data must be robust."

Journal of Medical Ethics editor, Professor John McMillan, adds: "Researchers face powerful headwinds against their efforts to further knowledge about COVID-19. The urgency for evidence, the rewards from finding a successful therapy or vaccine, and the prevalence of disinformation mean scientific integrity is critically important.

"Professor Bramstedt's report is an early warning for journals and preprint servers to be proactive and maintain rigour when assessing research."

Men predominate in more than 85% of COVID-19 decision-making and key advisory bodies around the globe, with gender parity in just 3.5%, reveals an analysis of the available data, published in the online journal BMJ Global Health.

This has become a "disturbingly accepted pattern of global health governance" that undermines the effectiveness of the pandemic response and ultimately costs lives, warn the authors.

There have been numerous global and national commitments to move towards gender-inclusive global health governance. But COVID-19 took the world by surprise, prompting many advisory groups and expert panels to be set up very quickly.

To find out just how gender inclusive and representative these bodies are, the authors collected information up to June 2020 on the membership of COVID-19 global and national decision-making and expert bodies for 193 UN Member States.

They did this through crowdsourcing, targeted searches of 'grey literature', such as unpublished research and policy statements, and outreach to national governments or World Health Organization (WHO) country offices.

Most of the information about membership, leadership, and areas of expertise was neither easily accessible nor publicly available, hampering efforts to obtain it and, "ultimately, the ability to hold countries accountable to previously made commitments," note the authors.

Their analysis included 115 expert and decision-making COVID-19 task forces from 87 countries. It revealed that men predominate in more than 85% of expert groups and task forces; women predominate in just over 1 in 10 (11.5%), with gender parity in a mere 3.5%. Similarly, 81% (65) were headed up by men at the time of the search.

Women make up 24%, 24%, and 37.5%, respectively, of the WHO's first, second, and third International Health Regulations Emergency Committees, for example.

And while expert groups more often had higher proportions of women or gender parity than decision-making committees, this most likely reflects potential societal biases and gender stereotyping around leadership, suggest the authors.

In the USA, for example, women make up just 9% of the White House Coronavirus Task Force, but 82.5% of the chief public health agency's COVID-19 Response Team.

The authors acknowledge that COVID-19 tends to be more severe and lethal among men. But women have been hit harder socially and economically, as a result of extended and unpaid caring responsibilities, heightened risk of domestic and sexual violence; and loss of access to maternal and reproductive health services during lockdown, they point out.

The Ebola and Zika pandemics were also associated with increased rates of maternal ill health and death as well as unwanted pregnancies and unsafe abortions, they note.

"A 'new default' mode of diverse and intersectional governance is sorely needed to face future crises head-on and guide a healthy and equitable COVID-19 recovery," they assert.

First, this should include truly representative membership of international and national task forces, spanning gender, ethnicity, race, culture, geography and disability.

Second, quick action in emergency scenarios is repeatedly used as a justification to sidestep transparency and restrict communication in the name of health security, when nothing could be further from the truth. "Closed-door governance" should be replaced by open and transparent communication and decision-making as the norm, they say.

And thirdly, data collection and governance policies must go beyond binary representation in order to produce results that are inclusive of the full gender spectrum.

"Reaching a critical mass of women in leadership - even as result of intentional selection or quotas - benefits governance processes through the disruption of groupthink, the introduction of novel viewpoints, a higher quality of monitoring and management, more effective risk management and robust deliberation," they write.

Countries with women at the helm have been associated with particularly effective COVID-19 responses, fewer cases, and lower death rates from the disease, they point out.

"Men dominating leadership positions in global health has long been the default mode of governing," excluding those "who offer unique perspectives, expertise and lived realities.

"This not only reinforces inequitable power structures but undermines an effective COVID-19 response - ultimately costing lives," they conclude.

Spinal cord injury often leads to permanent functional impairment. In a new study published in the journal Science researchers at Karolinska Institutet in Sweden show that it is possible to stimulate stem cells in the mouse spinal cord to form large amounts of new oligodendrocytes, cells that are essential to the ability of neurons to transmit signals, and thus to help repair the spinal cord after injury.

The spinal cord conveys signals from the brain to the rest of the body and spinal cord injury often leads to a degree of paralysis as some nerve fibers become transected and others, while intact, operate less efficiently. This impaired function is often caused by the loss of oligodendrocytes, a type of insulating cell that facilitates neuronal signalling.

In many organs, damaged tissue can be repaired by stem cells that create the cell types that have been lost. There are stem cells in the adult spinal cord, but these give rise primarily to scar forming cells after an injury. The scar tissue limits the extent of the damage but does not contribute to the replacement of lost cells.

In the current study, the researchers carefully characterised spinal cord stem cells at a genetic level in mice, and found that the stem cells' DNA was receptive to signals that stimulate the formation of new oligodendrocytes.

"We found that the stem cells were not locked into forming scar tissue and understood how we could nudge them in another direction to also form cells that contribute to repair," says the study's first author Enric Llorens-Bobadilla, researcher at the Department of Cell and Molecular Biology at Karolinska Institutet.

By controlling which genes were activated in the stem cells, the researchers were able to stimulate an abundant generation of new oligodendrocytes, which led to improved nerve fibre function in the damaged spinal cord.

"This shows that it's possible to affect stem cells in the nervous system so that they contribute more to functional recovery," says principal investigator Jonas Frisén, professor at the Department of Cell and Molecular Biology, Karolinska Institutet. "Although the studies were done in mice and are not directly translatable to humans, they indicate a conceptually new strategy for stimulating repair after damage to the nervous system."

A team of researchers, led by the University of Bristol, has revealed our most ancient ancestors were ecologically diverse, despite lacking jaws and paired fins.

Long before they evolved out of the water, our ancient ancestors were simple fish-like creatures, but without fins or chins, who survived by filtering nutrients from sediment.

They have long been thought of as the lazy lumps who spent most of their lives resting on or near to the sea floor. The belief was that everything changed with the evolution of jawed vertebrates whose paired fins made them the super-swimmers and active predators, driving their jawless relatives to extinction.

However, a new study published in the journal Current Biology overturns this classical evolutionary story.

Researchers from the University of Bristol used computer simulations to explore how avatars of our extinct ancestors interacted with water currents. These experiments revealed the bizarre spikes and spines that ornamented the heads of these jawless vertebrates were actually hydrodynamic adaptations, passively generating lift from water currents flowing over the body. The varying head shapes of different species allowed them to adapt to different positions, some high, others low, within the water. Our ancient ancestors were already ecologically diverse, long before the evolution of their jawed vertebrate relatives.

Dr Humberto G. Ferron, a postdoctoral researcher from the University of Bristol and one of the paper's co-authors, said: "The evolution of jaws and fins have classically been seen as the key evolutionary inventions that allowed vertebrates to diversify their lifestyles.

"In this context, jawless ancestors, characterized by the presence of heavy rigid headshields, were assumed to be cumbersome fish-like creatures, living on the bottom of rivers and seas, with poor manoeuvrability."

The question of how our ancient ancestors made a living has long been a mystery because there are no animals like them alive today. The 'osteostracans' (their latin name, meaning bony shells) were heavily armoured, encased in thick bone from snout to tail. They lacked a rear pair of legs and some had none at all; many possessed bizarre horn-like extensions from the front of their heads.

Ferrón and colleagues tackled this problem using state-of-the-art computational engineering techniques that simulate the behaviour of fossil avatars in water currents.

Dr Imran Rahman, from the Oxford University Museum of Natural History, said: "The application of computational fluid dynamics, has allowed us to study the swimming performance of ancient vertebrates and learn more about their position in evolutionary history.

Dr Carlos Martinez Perez, from the University of Valencia (Spain), added: "Our simulations reveal that the different species of osteostracans show equally different hydrodynamic efficiencies. Some of them performed better when moving close to the sea floor or riverbed while others performed better when swimming freely in the water."

Professor Phil Donoghue, another Bristol co-author, concluded: "The different species' body shapes are adapted to different environments, revealing distinct lifestyles among these groups of jawless early vertebrates.

"Our results calls into question the prevailing view that these extinct groups of jawless vertebrates were ecologically constrained, and reveals the main evolutionary hypothesis for the origin of jawed vertebrates is more complex than previously thought."