Variant hunters: the story behind the race to sequence COVID-19 genetics

 Hear from some of the scientists behind the UK’s nationwide sequencing effort to track SARS-CoV-2. Sir Patrick Vallance (the government’s Chief Scientific Adviser) also describes how the expertise that came together during the pandemic is now recognized across the world – and why it’s crucially important to continue to sequence to be ready for future pandemics.

This pioneering work is being carried out by the COVID-19 Genomics UK (COG-UK) consortium, which comprises numerous academic institutions, four public health agencies and the Wellcome Sanger Institute, and is administered by the University of Cambridge. “Incredibly impressive, incredibly high quality and incredibly focused on the mission to make sure that as many people benefited from the science as possible,” Sir Patrick Vallance.

The variant hunters are helping us to understand how and why the COVID-19 virus is spreading, allowing us to fight back against the COVID-19 pandemic.

Source/Credit: University of Cambridge

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Scientists reverse pancreatic cancer progression in ‘time machine’ made of human cells

 

Bumsoo Han, professor of mechanical engineering, has built a realistic model of a pancreatic structure that acts as a “time machine” to understand cancer and reverse its spread.
(Purdue University photo/John Underwood)

What makes pancreatic cancer so deadly is its covert and quick spread. Now, a “time machine” built by Purdue University engineers has shown a way to reverse the course of cancer before it spreads throughout the pancreas.

“These findings open up the possibility of designing a new gene therapy or drug because now we can convert cancerous cells back into their normal state,” said Bumsoo Han, a Purdue professor of mechanical engineering and program leader of the Purdue Center for Cancer Research. Han has a courtesy appointment in biomedical engineering.

The time machine that Han’s lab built is a lifelike reproduction of a pancreatic structure called the acinus, which produces and secretes digestive enzymes into the small intestine. Pancreatic cancer tends to develop from chronic inflammation that happens when a mutation has caused these digestive enzymes to digest the pancreas itself.

Increased infectiousness of coronavirus variants explained

 

Artist's impression of a mutating coronavirus

Researchers from the Universities of Oxford and Dundee have made a discovery that helps explain why variations in the virus causes COVID-19 to spread so rapidly.

Coronaviruses are so named because of the spikes on their surface that make it look like a crown, the Latin word for which is corona. The virus uses these spikes to attach to and enter cells, where they then replicate. All common SARS-CoV-2 variants have mutations in the part of their spike proteins that binds to cells.

The Oxford-Dundee team found that most, but not all, of the common mutations in spike individually strengthened binding to ACE2, a protein found on the surface of our cells.

Furthermore, ACE2 variants found naturally in humans were shown to strengthen binding between it and the virus, suggesting that individuals with common ACE2 variants could be more susceptible to COVID-19 infection.

Professor Anton van der Merwe, from the Sir William Dunn School of Pathology at the University of Oxford, said: 'The purpose of our study was to measure the precise effect of mutations in spike and ACE2 on the strength of their interaction.

'This is important because it helps us understand why some SARS-CoV-2 variants spread more rapidly and should also help us predict whether individuals with mutations in ACE2 would be more susceptible to COVID-19.

'Knowing the precise effect of spike mutations on binding to ACE2 helps us understand why SARS-CoV-2 variants spread more rapidly. This may inform our response to these new variants and help us identify potentially dangerous new variants before they spread widely.'

Even as the world recovers from the pandemic, more infectious variants of the coronavirus have emerged. The Alpha variant rapidly replaced all other variants in the UK and in other countries, while the Delta variant, which largely superseded it, continues to spread around the world. The Beta and Gamma variants also emerged in populations that had previously been infected with the original SARS-CoV-2 virus.

This has led scientists around the world to study these new variants to try and understand the properties which make them more infectious. This latest research has also shown that while common ACE2 mutations led to increased binding, this is not the case for all SARS-CoV-2 variants.

Professor Geoff Barton from Dundee’s School of Life Sciences, said: 'These results are a great example of how collaboration between experts in Computational Biology working with leading experimentalists can result in exciting new findings.

'The work sprang from a computational analysis carried out in our group at Dundee by Dr Stuart MacGowan on the effects of human ACE2 variants on SARS-CoV-2 binding. This helped the Oxford group to focus their complementary skills in the laboratory on the most important human and coronavirus variants.'

The paper is published today in eLife.

Source/Credit: University of Oxford

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Cannabis users at 'much higher' risk of developing poor mental health

 

Those with a recorded history of cannabis use in general practice records are at a much higher risk of developing mental ill health problems such as anxiety or depression as well as severe mental illnesses, new research shows.

The findings point to the need for a public health approach to the management of people misusing cannabis, including the need to emphasize the importance of general practitioners to continue enquiring about recreational drug use.

While the links between cannabis use and severe mental illnesses such as schizophrenia and psychosis are well researched, the associations are less clear between cannabis use as described in patient’s GP records and other, more common types of mental ill health such as depression and anxiety.

In a new study, published in Psychological Medicine, researchers in the University of Birmingham’s Institute for Mental Health and the Institute of Applied Health Research found a strong link between general practice recorded cannabis use and mental ill health in one of the largest cohorts ever explored.

Senior author Dr Clara Humpston said: “Cannabis is often considered to be one of the ‘safer’ drugs and has also shown promise in medical therapies, leading to calls for it be legalized globally. Although we are unable to establish a direct causal relationship, our findings suggest we should continue to exercise caution since the notion of cannabis being a safe drug may well be mistaken.”

Dr Joht Singh Chandan said: “The research reaffirms the need to ensure a public health approach to recreational drug use continues to be adopted across the UK. We must continue to progress measures to improve the prevention and detection of drug use as well as implement the appropriate supportive measures in an equitable manner to prevent the secondary negative health consequences.”

Using primary care data drawn from the IQVIA Medical Research Database (IMRD-UK), the researchers found following the first recorded use of cannabis, patients were three times more likely to develop common mental health problems such as depression and anxiety. In addition, they were almost 7 times more likely to develop severe mental illnesses such as psychosis or schizophrenia.

The dataset included records from 787 GP practices around the UK gathered over a 23-year period between 1995 and 2018. The researchers were able to include data from 28,218 patients who had a recorded exposure to cannabis. These were matched to 56,208 patients who had not been using cannabis and controlled for sex, age, ethnicity, smoking status and other relevant characteristics.

The cannabis users also had much higher rates of having a recorded history of using other drugs such as heroin, cocaine and amphetamines.

Future research in this area will investigate the levels of cannabis use or the potency of ingredients.

Source/Credit: University of Birmingham

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AI can predict cancer risk through mammograms

 

Two normal mammograms showing the difference between a dense breast (left)
 and a fatty breast (right).
Photo credit: National Cancer Institute

As a hereditary disease, breast cancer has affected hundreds of families throughout the state. Annually, an average of 1,190 women are diagnosed with breast cancer in Hawaiʻi. As October approaches in recognition of National Breast Cancer Awareness Month, new public impact research from the University of Hawaiʻi Cancer Center is using artificial intelligence (AI) to improve risk assessment for breast cancer to aid in prevention and early detection, improving breast cancer outcomes for women all over the world.

To reduce unnecessary imaging for breast cancer and costs associated with it, UH Cancer Center Researcher John Shepherd and his colleagues found that AI is able to distinguish between the mammograms of women who are more likely to develop breast cancer later on, and those who are not. The study was published in Radiology.

“Conventional methods of breast cancer risk assessment using clinical risk factors haven’t been that effective,” said Shepherd, study lead author and a professor in the Population Sciences in the Pacific Program (epidemiology). “We thought that there was more in the image than just breast density that would be useful for assessing risk.”

Deep learning model

Compared to commonly used clinical risk factors, a sophisticated type of AI called deep learning has been found to be better at using mammograms to differentiate between women who will and will not be diagnosed with breast cancer in the future. Typically, mammograms provide a measure of breast cancer risk through measurements of breast density. While denser breasts on mammography are associated with a higher risk of cancer, there are other factors hidden in mammograms that are likely to contribute risk.

The study used a data set of more than 25,000 digital screening mammograms from 6,369 women who participated in screening mammography from 2006 to 2014. The researchers trained the deep learning model to find details and signals in the mammogram that might be linked to increased cancer risk. When they tested the deep learning-based model, it underperformed in assessing the risk factors for interval cancer risk (cancers diagnosed between routine screenings), but outperformed clinical risk factors in determining screening-detected cancer risk.

“The results showed that the extra signal we’re getting with AI provides a better risk estimate for screening-detected cancer than other forms of assessment,” said Shepherd. “It helped us accomplish our goal of classifying women into low risk or high risk of screening-detected breast cancer.”

He added, “By ranking mammograms in terms of the probability of seeing cancer in the image, AI is going to be a powerful second reading tool to help categorize mammograms.”

Researchers are planning to replicate the study in Native Hawaiian and Pacific Islander women, two groups that have been underrepresented in breast cancer research. They also want to extend the work beyond cancer risk to look at the risk of different grades of breast cancer, from least to most aggressive.

Learn more about breast cancer causes, prevention, treatment and screening here.

Source/Credit: University of Hawaiʻi/John Shepherd

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Clinical trial produces effective oral antiviral to combat COVID-19

 

Scientists at the University of North Carolina at Chapel Hill say a twice-daily pill – molnupiravir — could change the way COVID-19 is treated. Today’s announcement by Merck Co. to seek emergency authorization by the Food and Drug Administration reflects research and testing conducted at UNC-Chapel Hill.

Strong clinical trial results showed the experimental COVID-19 pill reduced hospitalizations and deaths by half in people recently infected with coronavirus. Carolina began working on molnupiravir in 2016 and showed the drug could be a weapon against coronaviruses and future pandemics.

“This is a real game changer for a pandemic like COVID-19 because it allows us to treat people quicker with a method that’s convenient and accessible,” said William A. Fischer II, an associate professor of pulmonology and critical care at the UNC School of Medicine and director of emerging pathogens at the UNC Institute for Global Health and Infectious Diseases.

US Army backs ‘sleeping cap’ to help brains take out the trash

 

Rice University engineers, in collaboration with Houston Methodist and Baylor College of Medicine, are developing a noninvasive skullcap to better understand how the brain disposes of metabolic waste while the wearer sleeps. Signals will be acquired will be through electroencephalogram (EEG), rheoencephalography (REG), orbital sonography (OSG) and transcranial doppler (TCD), with modulation through transcranial/transcutaneous brain and nerve electrical simulations (TES) and low-intensity focused ultrasound pulses (LIFUP).
Illustration courtesy of the NeuroEngineering Initiative

How well does your sleeping brain prepare you for a new day? Researchers at Rice University backed by the U.S. Army Military Operational Medicine Research Program (MOMRP) are poised to find out.

Engineers at Rice University’s NeuroEngineering Initiative in partnership with the Institute of Biosciences and Bioengineering (IBB) and physicians at Houston Methodist Hospital and Baylor College of Medicine will develop a “sleeping cap” to analyze the cleansing flow of fluid that drains the brain of common metabolic waste during sleep.

Rice University engineers, in collaboration with Houston Methodist and Baylor College of Medicine, are developing a noninvasive skullcap to better understand how the brain disposes of metabolic waste while the wearer sleeps. Signals will be acquired will be through electroencephalogram (EEG), rheoencephalography (REG), orbital sonography (OSG) and transcranial doppler (TCD), with modulation through transcranial/transcutaneous brain and nerve electrical simulations (TES) and low-intensity focused ultrasound pulses (LIFUP). Illustration courtesy of the NeuroEngineering Initiative

Over a third of COVID-19 patients diagnosed with at least one long-COVID symptom

37% of people had at least one long-COVID symptom diagnosed in the 3-6 month period after COVID-19 infection. The most common symptoms were breathing problems, abdominal symptoms, fatigue, pain and anxiety/depression.

This new study from the University of Oxford and the National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre (BRC) investigated long-COVID in over 270,000 people recovering from COVID-19 infection, using data from the US-based TriNetX electronic health record network.

The study reports on how commonly nine core long-COVID symptoms were diagnosed, and how this rate compared to people recovering from influenza. The nine core long-COVID symptoms, occurring 90-180 days after COVID-19 was diagnosed, comprise:

Largest trial of antibiotic amoxicillin for treating chest infections in children finds little effect

 The largest randomized placebo-controlled trial of the antibiotic amoxicillin for treating chest infections in children - one of the most common acute illnesses treated in primary care in developed countries, has found it is little more effective at relieving symptoms than the use of no medication. The study, published in The Lancet and funded by the National Institute for Health Research (NIHR), was led by researchers from the University of Southampton and supported by centers at the Universities of Bristol, Oxford and Cardiff.

Although viruses are believed to cause many of these infections in children, whether or not antibiotics are beneficial in treatment of chest infections in children is still debated. While research so far in adults has shown that antibiotics are not effective for uncomplicated chest infections until now, there has not been the same level of research in children.

Researchers sought to test whether amoxicillin reduces the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) lower respiratory tract chest infections in primary care. The trial recruited 432 children aged six months to twelve years-old with acute uncomplicated chest infections from primary care practices in England and Wales who were then randomly assigned to receive either amoxicillin or a placebo three times a day for seven days. Doctors or nurse-prescribers assessed symptoms at the start of the study and parents, with help from their children where possible, completed a daily symptom diary.

Researchers target key protein to fight inflammatory disease

 

Photo by Ivan Samkov from Pexels

For the first time, researchers have identified key molecules within the immune system that may help fight the inflammation that drives chronic diseases including cancers, sepsis and brain disease.

The University of Queensland collaborated with the Indian Institute of Technology, Kanpur on the study.

UQ Professor Trent Woodruff said the research investigated the part of the immune system responsible for the body’s natural response to pathogens and injury, known as the ‘complement system’.

“When activated inappropriately, the system drives inflammatory diseases such as sepsis, COVID-19, stroke, heart attacks, cancers and brain illnesses,” Professor Woodruff said.

A key protein, known as C5aR2, is a potential therapeutic target for treating chronic disease, due to its ability to moderate many immune and inflammatory processes.

“It’s been really challenging for researchers to understand how this protein is activated due to its unusual structure,” Professor Woodruff said.

“Instead of coupling with cell-signaling proteins, C5aR2 instead relies on signal regulating proteins known as β-arrestin proteins.”

“Our study investigated interactions between the C5aR2 and β-arrestin proteins, while screening for molecules that activated a connection between the two”, Professor Woodruff said.

“We found key and specific cell signals present when the C5aR2 was activated, which may act to boost the immune system’s response in inflammation.”

Co-investigator Professor Arun Shukla said the findings provided a framework for further exploration of β-arrestin proteins for their therapeutic modulation in disease.

“We are now working to progress these research findings into disease models and potentially enable scientists to design novel drug molecules targeting C5aR2 to treat inflammatory disorders”.

This study is the journal Molecular Cell, as part of an international collaboration with Professor Arun Shukla, based in India, and researchers Asuka Inoue, based in Japan, and Stéphane A. Laporte in Canada.

Source/Credit: University of Queensland

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Dinosaurs' ascent driven by volcanoes powering climate change

 The rise of dinosaurs coincided with environmental changes driven by major volcanic eruptions over 230 million years ago, a new study reveals.

The Late Triassic Carnian Pluvial Episode (CPE) saw an increase in global temperature and humidity - creating a major impact on the development of animal and plant life, coinciding with the establishment of modern conifers.

Researchers analyzed sediment and fossil plant records from a lake in northern China’s Jiyuan Basin, matching pulses of volcanic activity with significant environmental changes, including the CPE’s ‘mega monsoon’ climate, some 234 million to 232 million years ago.

The international research team, including experts at the University of Birmingham, today published their findings in Proceedings of the National Academy of Sciences (PNAS) – revealing four distinct episodes of volcanic activity during this time period, with the most likely source being major volcanic eruptions from the Wrangellia Large Igneous Province, the remnants of which are preserved in western North America.

COVID-19 has caused the biggest decrease in life expectancy

The COVID-19 pandemic triggered life expectancy losses not seen since World War II in Western Europe and exceeded those observed around the dissolution of the Eastern Bloc in central and Eastern European countries, according to research published today, led by scientists at Oxford’s Leverhulme Center for Demographic Science.

The research team assembled an unprecedented dataset on mortality from 29 countries, spanning most of Europe, the US and Chile – countries for which official death registrations for 2020 had been published. They found that 27 of the 29 countries saw reductions in life expectancy in 2020, and at a scale which wiped out years of progress on mortality, according to the paper published today in the International Journal of Epidemiology.

Women in 15 countries and men in 10 countries were found to have a lower expectancy at birth in 2020 than in 2015, a year in which life expectancy was already negatively affected by a significant flu season.

According to the study’s co-lead author Dr José Manuel Aburto, ‘For Western European countries such as Spain, England and Wales, Italy, Belgium, among others, the last time such large magnitudes of declines in life expectancy at birth were observed in a single year was during WW-II.’

A new phase of matter

 Researchers from the University of Cambridge used computer modelling to study potential new phases of matter known as prethermal discrete time crystals (DTCs). It was thought that the properties of prethermal DTCs were reliant on quantum physics: the strange laws ruling particles at the subatomic scale. However, the researchers found that a simpler approach, based on classical physics, can be used to understand these mysterious phenomena.

Understanding these new phases of matter is a step forward towards the control of complex many-body systems, a long-standing goal with various potential applications, such as simulations of complex quantum networks. The results are reported in two joint papers in Physical Review Letters and Physical Review B.

When we discover something new, whether it’s a planet, an animal, or a disease, we can learn more about it by looking at it more and more closely. Simpler theories are tried first, and if they don’t work, more complicated theories or methods are attempted.  

“This was what we thought was the case with prethermal DTCs,” said Andrea Pizzi, a PhD candidate in Cambridge’s Cavendish Laboratory, first author on both papers. “We thought they were fundamentally quantum phenomena, but it turns out a simpler classical approach let us learn more about them.”

DTCs are highly complex physical systems, and there is still much to learn about their unusual properties. Like how a standard space crystal breaks space-translational symmetry because its structure isn’t the same everywhere in space, DTCs break a distinct time-translational symmetry because, when ‘shaken’ periodically, their structure changes at every ‘push’.

Physicists probe light smashups to guide future research

 

The Compact Muon Solenoid experiment at the
European Organization for Nuclear Research’s
Large Hadron Collider.
Photo courtesy of CERN

Hot on the heels of proving an 87-year-old prediction that matter can be generated directly from light, Rice University physicists and their colleagues have detailed how that process may impact future studies of primordial plasma and physics beyond the Standard Model.

“We are essentially looking at collisions of light,” said Wei Li, an associate professor of physics and astronomy at Rice and co-author of the study published in Physical Review Letters.

Rice physicists teamed with colleagues at Europe’s Large Hadron Collider to study matter-generating collisions of light. Researchers showed the departure angle of debris from the smashups is subtly distorted by quantum interference patterns in the light prior to impact. Illustration by 123rf.com

“We know from Einstein that energy can be converted into mass,” said Li, a particle physicist who collaborates with hundreds of colleagues on experiments at high-energy particle accelerators like the European Organization for Nuclear Research’s Large Hadron Collider (LHC) and Brookhaven National Laboratory’s Relativistic Heavy Ion Collider (RHIC).

Accelerators like RHIC and LHC routinely turn energy into matter by accelerating pieces of atoms near the speed of light and smashing them into one another. The 2012 discovery of the Higgs particle at the LHC is a notable example. At the time, the Higgs was the final unobserved particle in the Standard Model, a theory that describes the fundamental forces and building blocks of atoms.

Impressive as it is, physicists know the Standard Model explains only about 4% of the matter and energy in the universe. Li said this week’s study, which was lead-authored by Rice postdoctoral researcher Shuai Yang, has implications for the search for physics beyond the Standard Model.

Major advance in race for SARS-CoV-2 inhibitor drugs

 

Mpro dimer from SARS-CoV-2 in complex with the inhibitory peptide (13)
 following 100 ns of molecular dynamics simulation.
Credit: University of Bristol

A new advance towards the development of drugs specifically designed to inhibit a key SARS-CoV-2 enzyme is reported in the Royal Society of Chemistry's leading journal, Chemical Science. The international team, led by scientists from the Universities of Oxford and Bristol, has designed new peptide molecules and shown that they block (inhibit) the virus’s main protease [Mpro] - a prominent SARS-CoV-2 drug target.

Once SARS-CoV-2 invades a healthy human cell, the virus's own genetic material commandeers the infected cell's machinery, forcing it to make new copies of the virus. A vital step in this viral life cycle involves cutting a very long 'polyprotein' into its constituent viral proteins. SARS-CoV-2 has two molecular machines called protease enzymes that act as 'molecular scissors'. One of these, called the main protease, or 'Mpro' for short, has the vital role of chopping up the polyprotein, cutting it at 11 different places.

In the early days of the pandemic lockdown, Professor Garrett Morris at the University of Oxford, brought together a group of scientists to try to understand Mpro, with the aim of helping develop drugs against COVID-19. Meeting weekly over many months by Zoom, this group combined their computational and experimental expertise, and grew to include scientists from several different countries. From Bristol, this included Professors Adrian Mulholland and Jim Spencer, Dr Deborah Shoemark, PhD student Becca Walters, and other colleagues. Using a wide array of computational molecular modelling techniques including interactive molecular dynamics in virtual reality, quantum mechanics, peptide design and protein-ligand interaction analysis, the scientists were able to build an atomic level picture of the structure, dynamics and interactions of Mpro.

From these models, the team were able to find how the viral Mpro 'molecular scissors' work. They then designed new peptides, which are short pieces of protein, as inhibitors, to bind tightly to Mpro and prevent it from working, stopping the virus dead in its tracks. But did they work?

All 11 protein cut sites and four of these designed peptides were synthesized and tested in the Chemistry Research Laboratory at the University of Oxford. Experiments, led by Professor Chris Schofield at Oxford, showed that the novel peptides - designed by Dr Deborah Shoemark, with software developed in Bristol - not only bound to the molecular scissors, but they outcompeted the natural protein cut sites and so inhibited Mpro.

Adrian Mulholland, Professor of Chemistry at the University of Bristol and one of the study's lead authors, said: "Despite the development of successful vaccines in record time, new antiviral drugs are desperately needed. To date there are no drugs designed specifically to target COVID-19. Computational molecular modelling can really help with this. As we’ve shown here, computational design can produce molecules that actually stop the Mpro enzyme from working."

Dr Deborah Shoemark, Senior Research Associate (Biomolecular Modelling) in the School of Biochemistry, added: "It has been great to work together on this, combining our ideas and methods to get a really detailed picture of how this viral enzyme works – and to design molecules that actually stop it from working. Understanding Mpro specificity provides the potential to exploit vulnerabilities of the SARS-CoV-2 virus that may provide routes to new antivirals."

Professor Mulholland added: "This collaboration has really shown how sharing of models, data and expertise can help get understanding and make progress much more quickly. Garrett (Morris) built a fantastic team, and it has been exciting to work together on this. It’s how science should be done – particularly in the face of pressing problems like the COVID-19 pandemic."

The study was funded through several grants including support from the EPSRC, BBSRC and the Wellcome Trust.

Source/Credit: University of Bristol

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High-speed alloy creation might revolutionize hydrogen’s future

 

Researchers from Sandia National Laboratories and international collaborators used computational approaches, including explainable machine learning models, to elucidate new high-entropy alloys with attractive hydrogen storage properties and direct laboratory synthesis and validation.

A Sandia National Laboratories team of materials scientists and computer scientists, with some international collaborators, have spent more than a year creating 12 new alloys — and modeling hundreds more — that demonstrate how machine learning can help accelerate the future of hydrogen energy by making it easier to create hydrogen infrastructure for consumers.

Vitalie Stavila, Mark Allendorf, Matthew Witman and Sapan Agarwal are part of the Sandia team that published a paper detailing its approach in conjunction with researchers from Ångström Laboratory in Sweden and Nottingham University in the United Kingdom.

“There is a rich history in hydrogen storage research and a database of thermodynamic values describing hydrogen interactions with different materials,” Witman said. “With that existing database, an assortment of machine-learning and other computational tools, and state-of-the art experimental capabilities, we assembled an international collaboration group to join forces on this effort. We demonstrated that machine learning techniques could indeed model the physics and chemistry of complex phenomena which occur when hydrogen interacts with metals.”

Having a data-driven modeling capability to predict thermodynamic properties can rapidly increase the speed of research. In fact, once constructed and trained, such machine learning models only take seconds to execute and can therefore rapidly screen new chemical spaces: in this case 600 materials that show promise for hydrogen storage and transmission.

“This was accomplished in only 18 months,” Allendorf said. “Without the machine learning it could have taken several years. That’s big when you consider that historically it takes something like 20 years to take a material from lab discovery to commercialization.”

Autistic individuals are more likely to be LGBTQ+

The findings have important implications for the healthcare and support of autistic individuals. The results are published in the journal Autism Research.  

For many years it was wrongly assumed that autistic individuals are uninterested in sexual or romantic relationships, but this is not the case. In recent years, small studies have suggested that autistic individuals are more likely to experience a wider diversity of sexual orientations and are less likely to have sexually transmitted infections (STIs). However, the existing evidence has been limited in size and scope.

In the largest study to date on these topics, the team at the Autism Research Center used an anonymous, self-report survey to study the sexual activity, sexual orientation, and sexual health of autistic adults. Overall, 1,183 autistic and 1,203 non-autistic adolescents and adults (aged 16-90 years) provided information about their sexual activity, sexual orientation, and medical history of STIs.

The results showed that the majority of autistic adults (70% of autistic males and 76% of autistic females) engage in sexual activity—although they do so to a lesser degree than their non-autistic peers (89% of both non-autistic males and females report engaging in sexual activity). In contrast to previous findings, the results also found that there were no differences in likelihood of ever contracting an STI, or the age at which participants first engaged in sexual activity, between autistic and non-autistic individuals.

In addition, the study found that autistic adults and adolescents are approximately eight times more likely to identify as asexual and ‘other’ sexuality than their non-autistic peers. And there were sex differences in sexual orientation: autistic males are 3.5 times more likely to identify as bisexual than non-autistic males, whereas autistic females are three times more likely to identify as homosexual than autistic females.

When comparing autistic females and males directly, autistic females were more likely to be sexually active; more likely to identify as asexual, bisexual, and ‘other’ sexuality; and were less likely to identify as heterosexual.

Elizabeth Weir, a PhD candidate at the Autism Research Center in Cambridge, and the lead researcher of the study, said: “Understanding the intersectional identities of autistic individuals who are asexual, bisexual, homosexual, or ‘other’ sexuality is key. It is particularly important that healthcare providers and educators use language that is affirming and accepting of all sexual orientations and gender identities when providing sexual education and sexual health screening checks to autistic and non-autistic people alike.” 

Dr Carrie Allison, Director of Strategy at the Autism Research Center and a member of the team, said: “We must ensure that autistic individuals are receiving equal access to healthcare and support in their choices in their personal lives, to enjoy fulfilling lives and good mental health.”

Professor Simon Baron-Cohen, Director of the Autism Research Center and a member of the team, said: “This new study is an important example of applied health research with policy relevance for health and social care services.”

Source/Credit: University of Cambridge

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Treatments that may protect eggs against ageing

 

The spindle is responsible for separating the chromosomes equally when the oocyte goes through specialist meiotic cell divisions. The spindle is made of fibers called microtubules (green) to which the chromosomes (red) are attached. The use of MitoQ or BGP-15 improves the organization of the microtubules and alignment of the chromosomes to the center of the spindle. The oocyte has an improved chance of properly separating chromosomes and thereby avoiding aneuploidy when the egg is activated by the fertilizing sperm.

A woman’s fertility decreases as she ages – largely because of fewer healthy oocytes or eggs, and those that are available for fertilization often have chromosomal abnormalities which result in a higher incidence of miscarriage and genetic disorders such as Down’s syndrome.

Now a team at the Monash Biomedicine Discovery Institute (BDI) and Robinson Research Institute, collaborating with Monash IVF, has found a potential treatment that targets mitochondria to help prevent these chromosomal errors in mouse and human eggs.

In a paper published in the journal Human Reproduction, researchers led by Professors John Carroll and Rebecca Robker used two mitochondria-targeted therapeutics – called MitoQ and BGP-15 – which appeared to protect eggs from the chromosomal disturbances seen in older or abnormal eggs.

In particular, the addition of these agents improved how immature human eggs organize their chromosomes when matured in laboratory conditions. If this effect holds true for eggs maturing in the body it may also prevent chromosomal abnormalities in human eggs, effectively protecting them against miscarriage or genetic consequences such as Down’s syndrome.

The first author, Dr Usama Al-Zubaidi from the Monash BDI says: “Given that increasing numbers of women delay childbearing there is an imperative to improve fertility and reduce miscarriage and chromosomal anomalies associated with maternal ageing.”

The study identified “two excellent candidates that may one day help to improve fertility in older women.”

The age-related decline in fertility is strongly attributed to ovarian ageing, diminished ovarian reserves, and a decline in oocyte quality. One cause of this is due to increased oxidative stress within the oocytes.

Mitochondria – whether in an oocyte or any other cell in the body - use oxygen to create energy and one of the by-products is the production of free radicals. Oocytes are made during fetal life so have a lot of time to accumulate oxidative damage. Also, as eggs age, their defenses against oxidative damage become compromised. MitoQ and BGP-15 appear to be protecting eggs at least in part by improving mitochondrial function and minimizing oxidative stress during critical periods when the eggs are dividing their chromosomes.

Next steps involve finding the best conditions for these therapies to work when eggs are maturing inside the ovary and if the effects seen on chromosome organization translate into healthier eggs that have a better chance to develop into healthy pregnancies.

“Increasingly, fertility science is turning to therapies that specifically target these mitochondria with a view to preventing the chromosomal abnormalities that occur due to ageing and oxidative stress,” Professor Carroll said.

“Our study looked at two of these candidates to see whether they in fact made a difference to older eggs from humans and mice and found they can make the older eggs ‘younger’ again.” They were very effective at one level, but we are now working on seeing if this approach can work in patients.”

Both MitoQ and BGP-15 are used in humans already, – with MitoQ used to treat age associated hypertension while BGP-15 has been used in clinical trials for diabetes where it was given orally.

Medical Director Monash IVF, Professor Luk Rombauts said that improving function of the mitochondria, which he calls “the little energy factories within the eggs”, is one of the potential strategies to enhance egg quality and reproductive success, even more so in older women. “Monash IVF is keen to continue its collaboration with Professor John Carroll’s lab to find meaningful ways to turn this research into new treatment strategies.”

Source/Credit: Monash University

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Plasma doesn’t help severely ill COVID-19 patients

 

Giving severely ill COVID-19 patients a transfusion of blood from donors who have already recovered from the virus did not help them improve — and in some cases made them sicker, according to a major Canadian-led clinical trial reporting results in Nature Medicine.

“Convalescent plasma had been found to boost immunity in patients infected with some other viral entities, including SARS, in the past,” said local principal investigator Susan Nahirniak, professor of laboratory medicine and pathology in the University of Alberta’s Faculty of Medicine & Dentistry and medical/scientific lead for the Alberta Precision Laboratories transfusion and transplantation medicine program.

“But this trial did not demonstrate any benefit in terms of changing the course for patients who were admitted to hospital needing oxygen for SARS-CoV-2,” Nahirniak said. “It did not prevent intubation or death.”

The randomized controlled study followed 921 COVID-19 patients in Canada, the United States and Brazil who were admitted to hospital within 12 days of the onset of their respiratory symptoms. Two-thirds (614 patients) received convalescent plasma transfusions and one-third (307 patients) did not.

Of the convalescent plasma group, 199 of the patients required intubation or died, while 86 patients in the control group had these outcomes. Patients in the convalescent arm also experienced more serious adverse events such as needing more oxygen or worsening respiratory failure. The trial was terminated early when researchers realized the outcomes were not positive.

Varying immune responses

Another finding of the trial was that the level of neutralizing antibodies, or titres, in the blood of recovered COVID-19 patients was highly variable, which may have implications for how the population responds to vaccination.

“We were finding that several of the people who had signed up as donors were dropping their titres fairly quickly, so maintaining that donor pool was a challenge,” said Nahirniak. 

“It is proof that just because you’ve had COVID once doesn’t mean you can’t have it again,” she said. “It reinforces the need to be vigilant and possibly give boosters, similar to what we do with influenza.”

At the same time, the research team found that some donors had higher levels of non-functional antibodies against the virus’s spike protein. They reported that recipients of this plasma seemed to have poorer outcomes and recommended continued research on the prevalence and impact of these antibodies.

“If COVID is part of our lives going forward and there are certain antibodies that could be potentially harmful, is that something we need to be testing for and screening out for plasma donors?” Nahirniak posited.

Nahirniak noted that participating in the trial during the early days of the COVID-19 pandemic, when few treatments had been identified, helped to boost morale for both patients and clinical staff.

“We felt like we could do nothing, so at least this was an option, identifying the patients early on and getting them monitored.”

Nahirniak noted she was surprised by the disappointing results, but “that’s why we do a trial — we anticipated better success against the virus.”

The study was funded by the Canadian Institutes of Health Research and numerous local health agencies, including the University of Alberta Hospital Foundation and Alberta Health Services.

Source/Credit: University of Alberta

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Targeting tickborne diseases

"Benedict Khoo" Source: University of Minnesota

For Benedict Khoo, making a breakthrough discovery in health-related research doesn’t mean much if it can’t be put to use bettering people’s lives.

For Benedict Khoo, making a breakthrough discovery in health-related research doesn’t mean much if it can’t be put to use bettering people’s lives.

He knows from experience. When he worked in a research lab in Ohio, he felt “divorced from having a tangible impact,” due largely to regulatory hurdles in the field.

But that all changed when he turned to public health. There, he says, however his work turns out, he learns something that could help people make their own health decisions or influence policies. 

“That’s what drove me—to have that impact on the world and feel like I’m doing something,” says Khoo, a doctoral student in the School of Public Health (SPH). 

He found his niche with Jonathan Oliver, an assistant professor of environmental health sciences in SPH, who is now his adviser. Together they study the prevalence of Lyme disease and other tickborne diseases of humans, in a study area comprising Minnesota and adjacent northern Iowa and western Wisconsin.