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Study shows brain differences in interpreting physical signals in mental health disorders

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The researchers, from the University of Cambridge, found that the part of the brain which interprets physical signals from the body behaves differently in people with a range of mental health disorders, suggesting that it could be a target for future treatments.

The researchers studied ‘interoception’ – the ability to sense internal conditions in the body – and whether there were any common brain differences during this process in people with mental health disorders. They found that a region of the brain called the dorsal mid-insula showed different activity during interoception across a range of disorders, including depression, schizophrenia, eating disorders and anxiety disorders.

Many people with mental health disorders experience physical symptoms differently, whether that’s feeling uncomfortably full in anorexia, or feeling like you don’t have enough air in panic disorder.

The results, reported in The American Journal of Psychiatry, show that activity in the dorsal mid-insula could drive these different interpretations of bodily sensations in mental health. Increased awareness of the differences in how people experience physical symptoms could also be useful to those treating mental health disorders.

We all use exteroception – sight, smell, hearing, taste and touch – to navigate daily life. But interoception – the ability to interpret signals from our body – is equally important for survival, even though it often happens subconsciously.

“Interoception is something we are all doing constantly, although we might not be aware of it,” said lead author Dr Camilla Nord from the MRC Cognition and Brain Sciences Unit. “For example, most of us are able to interpret the signals of low blood sugar, such as tiredness or irritability, and know to eat something. However, there are differences in how our brains interpret these signals.”

Differences in interoceptive processes have previously been identified in people with eating disorders, anxiety and depression, panic disorder, addiction and other mental health disorders. Theoretical models have suggested that disrupted cortical processing drives these changes in interoceptive processing, conferring vulnerability to a range of mental health symptoms.

Nord and her colleagues combined brain imaging data from previous studies and compared differences in brain activity during interoception between 626 patients with mental health disorders and 610 healthy controls. “We wanted to find out whether there is something similar happening in the brain in people with different mental disorders, irrespective of their diagnosis,” she said.

Their analysis showed that for patients with bipolar, anxiety, major depression, anorexia and schizophrenia, part of the cerebral cortex called the dorsal mid-insula showed different brain activation when processing pain, hunger and other interoceptive signals when compared to the control group.

The researchers then ran a follow-up analysis and found that the dorsal mid-insula does not overlap with regions of the brain altered by antidepressant drugs or regions altered by psychological therapy, suggesting that it could be studied as a new target for future therapeutics to treat differences in interoception.

“It’s surprising that in spite of the diversity of psychological symptoms, there appears to be a common factor in how physical signals are processed differently by the brain in mental health disorders,” said Nord. “It shows how intertwined physical and mental health are, but also the limitations of our diagnostic system – some important factors in mental health might be ‘transdiagnostic’, that is, found across many diagnoses.”

In future, Dr Nord is planning studies to test whether this disrupted activation could be altered by new treatments for mental health disorders, such as brain stimulation.

The research was supported by NIHR Cambridge Biomedical Research Centre.

Reference:
Camilla L. Nord, Rebecca P. Lawson and Tim Dalgleish. ‘Disrupted dorsal mid-insula activation during interoception across psychiatric disorders.’ The American Journal of Psychiatry (2021). DOI: 10.1176/appi.ajp.2020.20091340

 

Researchers have shown why people with mental health disorders, including anorexia and panic disorders, experience physical signals differently.

Neurosciencebrainmental healthsensesCamilla NordCambridge University Health PartnersMRC Cognition and Brain Sciences UnitSchool of Clinical MedicineIn spite of the diversity of psychological symptoms, there appears to be a common factor in how physical signals are processed differently by the brain in mental health disorders: it shows how intertwined physical and mental health areCamilla NordGeralt from PixabayBinary code


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Targeting cellular response to SARS-CoV-2 holds promise as new way to fight infection

Thu, 17/06/2021 - 19:00

When a person is infected with SARS-CoV-2, the virus that causes COVID-19, it invades their cells and uses them to replicate - which puts the cells under stress. Current approaches to dealing with infection target the virus itself with antiviral drugs. But Cambridge scientists have switched focus to target the body’s cellular response to the virus instead. 

In a new study, published today in the journal PLOS Pathogens, they found that all three branches of a three-pronged signalling pathway called the ‘unfolded protein response’ (UPR) are activated in lab-grown cells infected with SARS-CoV-2. Inhibiting the UPR to restore normal cell function using drugs was also found to significantly reduce virus replication.

“The virus that causes COVID-19 activates a response in our cells - called the UPR - that enables it to replicate,” said Dr Nerea Irigoyen in the University of Cambridge’s Department of Pathology, senior author of the report.

She added: “Using drugs we were able to reverse the activation of this specific cellular pathway, and remarkably this reduced virus production inside the cells almost completely, which means the infection could not spread to other cells. This has exciting potential as an anti-viral strategy against SARS-CoV-2.” 

Treatment with a drug that targets one prong of the UPR pathway had some effect in reducing virus replication. But treatment with two drugs together - called Ceapin-A7 and KIRA8 - to simultaneously target two prongs of the pathway reduced virus production in the cells by 99.5%. This is the first study to show that the combination of two drugs has a much greater effect on virus replication in cells than a single drug. 

The approach would not stop a person getting infected with the coronavirus, but the scientists say symptoms would be much milder, and recovery time would be quicker.

Anti-viral drugs currently in use to treat COVID-19, such as remdesivir, target replication of the virus itself. But if the virus develops resistance to these drugs they will no longer work. In contrast, the new treatment targets the response of the infected cells; this will not change even if new variants emerge, because the virus needs this cellular response in order to replicate.

The next step is to test the treatment in mouse models. The scientists also want to see whether it works against other viruses, and illnesses such as pulmonary fibrosis and neurological disorders that also activate the UPR response in cells. 

“We hope this discovery will enable the development a broad-spectrum anti-viral drug, effective in treating infections with other viruses as well as SARS-CoV-2. We’ve already found it has an effect on Zika virus too. It has the potential to have a huge impact,” said Irigoyen.

SARS-CoV-2 is the novel coronavirus responsible for the COVID-19 pandemic. Since the end of 2019 there have been over 150 million cases of the disease worldwide, and over 3 million people have died. 

This research was funded by an Isaac Newton Trust/Wellcome Trust ISSF/University of Cambridge Joint Research Grant.

Reference
Echavarria-Consuegra, L. et al: ‘Manipulation of the unfolded protein response: a pharmacological strategy against coronavirus infection.’ PLOS Pathogens. May 2021. DOI:10.1371/journal.ppat.1009644

 

A new treatment approach focused on fixing cell damage, rather than fighting the virus directly, is effective against SARS-CoV-2 in lab models. If found safe for human use, this anti-viral treatment would make COVID-19 symptoms milder and speed up recovery times.

CoronavirusCOVID-19Infectious diseasesNerea IrigoyenDepartment of PathologyCambridge Infectious DiseasesSchool of the Biological SciencesCredit: NIAIDScanning electron microscope image of SARS-CoV-2 (orange) emerging from the surface of cells (green) cultured in the lab.


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Study identifies trigger for ‘head-to-tail’ axis development in human embryo

Thu, 17/06/2021 - 10:06

The second week of gestation represents a critical stage of embryo development, or embryogenesis. Failure of development during this time is one of the major causes of early pregnancy loss. Understanding more about it will help scientists to understand how it can go wrong, and take steps towards being able to fix problems.

The pre-implantation period, before the developing embryo implants into the mother’s womb, has been studied extensively in human embryos in the lab. On the seventh day the embryo must implant into the womb to survive and develop. Very little is known about the development of the human embryo once it implants, because it becomes inaccessible for study.

Pioneering work by Professor Magdalena Zernicka-Goetz and her team developed a technique, reported in 2016, to culture human embryos outside the body of the mother beyond implantation. This enabled human embryos to be studied up to day 14 of development for the first time. 

In a new study, the team collaborated with colleagues at the Wellcome Sanger Institute to reveal what happens at the molecular level during this early stage of embryogenesis. Their findings provide the first evidence that a group of cells outside the embryo, known as the hypoblast, send a message to the embryo that initiates the development of the head-to-tail body axis. 

When the body axis begins to form, the symmetrical structure of the embryo starts to change. One end becomes committed to developing into the head end, and the other the ‘tail’. 

The new results, published today in the journal Nature Communications, reveal that the molecular signals involved in the formation of the body axis show similarities to those in animals, despite significant differences in the positioning and organisation of the cells.

“We have revealed the patterns of gene expression in the developing embryo just after it implants in the womb, which reflect the multiple conversations going on between different cell types as the embryo develops through these early stages,” said Professor Magdalena Zernicka-Goetz in the University of Cambridge’s Department of Physiology, Development and Neuroscience, and senior author of the report.

She added: “We were looking for the gene conversation that will allow the head to start developing in the embryo, and found that it was initiated by cells in the hypoblast – a disc of cells outside the embryo. They send the message to adjoining embryo cells, which respond by saying ‘OK, now we’ll set ourselves aside to develop into the head end.’”

The study identified the gene conversations in the developing embryo by sequencing the code in the thousands of messenger RNA molecules made by individual cells. They captured the evolving molecular profile of the developing embryo after implantation in the womb, revealing the progressive loss of pluripotency (the ability of the embryonic cells to give rise to any cell type of the future organism) as the fates of different cells are determined.

“Our goal has always been to enable insights to very early human embryo development in a dish, to understand how our lives start. By combining our new technology with advanced sequencing methods we have delved deeper into the key changes that take place at this incredible stage of human development, when so many pregnancies unfortunately fail,” said Zernicka-Goetz.

This research was funded by Wellcome. It was carried out with the oversight of the UK Human Fertilisation and Embryology Authority, and with permission from a local research ethics committee.

Reference: Mole, M.A. et al: ‘A single cell characterisation of human embryogenesis identifies pluripotency transitions and putative anterior hypoblast centre.’ Nature Communications, June 2021. DOI: 10.1038/s41467-021-23758-w 

 

Scientists have identified key molecular events in the developing human embryo between days 7 and 14 - one of the most mysterious, yet critical, stages of our development. 

ReproductionMagdalena Zernicka-GoetzWellcome Sanger InstituteDepartment of Physiology, Development and Neuroscience (PDN)Cambridge Reproduction Strategic Research InitiativeSchool of the Biological SciencesWe have revealed the patterns of gene expression in the developing embryo just after it implants in the wombMagdalena Zernicka-GoetzHuman embryo in the lab 9 days after fertilisation.


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Teenagers at greatest risk of self-harming could be identified almost a decade earlier

Tue, 15/06/2021 - 07:00

The team, based at the MRC Cognition and Brain Sciences Unit, University of Cambridge, found that while sleep problems and low self-esteem were common risk factors, there were two distinct profiles of young people who self-harm – one with emotional and behavioural difficulties and a second group without those difficulties, but with different risk factors.

Between one in five and one in seven adolescents in England self-harms, for example by deliberately cutting themselves. While self-harm is a significant risk factor for subsequent suicide attempts, many do not intend suicide but face other harmful outcomes, including repeatedly self-harming, poor mental health, and risky behaviours like substance abuse. Despite its prevalence and lifelong consequences, there has been little progress in the accurate prediction of self-harm.

The Cambridge team identified adolescents who reported self-harm at age 14, from a nationally representative UK birth cohort of approximately 11,000 individuals. They then used a machine learning analysis to identify whether there were distinct profiles of young people who self-harm, with different emotional and behavioural characteristics. They used this information to identify risk factors from early and middle childhood. The results are published in the Journal of the American Academy of Child and Adolescent Psychiatry.

Because the data tracked the participants over time, the researchers were able to distinguish factors that appear alongside reported self-harm behaviour, such as low self-esteem, from those that precede it, such as bullying.

The team identified two distinct subgroups among young people who self-harm, with significant risk factors present as early as age five, nearly a decade before they reported self-harming. While both groups were likely to experience sleep difficulties and low self-esteem reported at age 14, other risk factors differed between the two groups.

The first group showed a long history of poor mental health, as well as bullying before they self-harmed. Their caregivers were more likely to have mental health issues of their own.

For the second group, however, their self-harming behaviour was harder to predict early in childhood. One of the key signs was a greater willingness to take part in risk-taking behaviour, which is linked to impulsivity. Other research suggests these tendencies may predispose the individual towards spending less time to consider alternate coping methods and the consequences of self-harm. Factors related to their relationships with their peers were also important for this subgroup, including feeling less secure with friends and family at age 14 and a greater concern about the feelings of others as a risk factor at age 11.

Stepheni Uh, a Gates Cambridge Scholar and first author of the study, said: “Self-harm is a significant problem among adolescents, so it’s vital that we understand the nuanced nature of self-harm, especially in terms of the different profiles of young people who self-harm and their potentially different risk factors.

“We found two distinct subgroups of young people who self-harm. The first was much as expected – young people who experience symptoms of depression and low self-esteem, face problems with their families and friends, and are bullied. The second, much larger group was much more surprising as they don’t show the usual traits that are associated with those who self-harm.”

The researchers say that their findings suggest that it may be possible to predict which individuals are most at risk of self-harm up to a decade ahead of time, providing a window to intervene.

Dr Duncan Astle said: “The current approach to supporting mental health in young people is to wait until problems escalate. Instead, we need a much better evidence base so we can identify who is at most risk of mental health difficulties in the future, and why. This offers us the opportunity to be proactive, and minimise difficulties before they start.

“Our results suggest that boosting younger children’s self-esteem, making sure that schools implement anti-bullying measures, and providing advice on sleep training, could all help reduce self-harm levels years later.

“Our research gives us potential ways of helping this newly-identified second subgroup. Given that they experience difficulties with their peers and are more willing to engage in risky behaviours, then providing access to self-help and problem-solving or conflict regulation programmes may be effective.”

Professor Tamsin Ford from the Department of Psychiatry added: “We might also help at-risk adolescents by targeting interventions at mental health leaders and school-based mental health teams. Teachers are often the first people to hear about self-harm but some lack confidence in how to respond. Providing them with training could make a big difference.”

The research was supported by the Gates Cambridge Trust, Templeton World Charity Foundation, and the UK Medical Research Council.

Reference
Uh, S et al. Two pathways to self-harm in adolescence. Journal of the American Academy of Child and Adolescent Psychiatry; 14 June 2021; DOI: 10.1016/j.jaac.2021.03.010

Researchers have identified two subgroups of adolescents who self-harm and have shown that it is possible to predict those individuals at greatest risk almost a decade before they begin self-harming.

mental healthChildrenrisk factorSpotlight on neuroscienceNeuroscienceDuncan AstleStepheni UhTamsin FordMedical Research CouncilGates Cambridge TrustTempleton World Charity FoundationMRC Cognition and Brain Sciences UnitDepartment of PsychiatrySchool of Clinical MedicineThe current approach to supporting mental health in young people is to wait until problems escalate. Instead, we need a much better evidence base so we can identify who is at most risk of mental health difficulties in the future, and whyDuncan AstleAdrien OlichonA man sitting in front of a screen


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New risk calculator to help save many more lives from heart attack and stroke

Mon, 14/06/2021 - 00:12

The risk calculator, SCORE2, will be adopted by the upcoming European Guidelines on Cardiovascular Disease Prevention in Clinical Practice, and enables doctors across Europe to predict who’s at risk of having a heart attack or stroke in the next 10 years with greater accuracy.

The researchers say this new prediction tool will help save many more people across Europe from having a potentially deadly heart attack or stroke, ultimately saving lives. People who are flagged as having an increased risk can be put on personalised preventative treatment, such a statins, or will receive lifestyle advice to lower their risk.

Researchers from the University of Cambridge played a leading role in a major collaborative effort involving around 200 investigators to develop SCORE2. Researchers across Europe analysed data from nearly 700,000 participants - mostly middle-aged - from 45 different studies. The tool has also been tailored for use in different European countries.

Participants had no prior history of heart and circulatory disease when they were recruited to the studies, and in the 10 years they were followed up, 30,000 had a ‘cardiovascular event’ – including fatal or non-fatal heart attack or stroke.

The risk tool was then statistically ‘recalibrated’, by using regional-specific cardiovascular and risk factor data from 10.8 million people, to more accurately estimate cardiovascular risk for populations split into four European risk regions. The tool uses known risk factors for heart and circulatory diseases such as age, sex, cholesterol levels, blood pressure and smoking.

This is a much-needed upgrade from the previous prediction tool that was developed using data before 1986 and underestimated the cardiovascular risk in some countries. The new SCORE2 risk calculator now accounts for current trends in heart and circulatory diseases, can predict both fatal and non-fatal conditions and is adaptable to countries with different levels of risk.

The researchers say that this upgrade will better estimate the cardiovascular risk amongst younger people, and will improve how treatment is tailored for older people and those in high-risk regions across Europe.

Professor Emanuele Di Angelantonio at the University of Cambridge British Heart Foundation (BHF) Centre of Research Excellence, said: “This risk tool is much more powerful and superior than what doctors have used for decades. It will fit seamlessly into current prevention programmes with substantial real-world impact by improving the prevention of cardiovascular diseases across Europe before they strike.”

Dr Lisa Pennells, also at Cambridge’s BHF Centre of Research Excellence, said: “This project was a highly collaborative effort that has brought together key experts and extensive data sources to develop improved risk prediction tools for cardiovascular disease for use across the UK and Europe.

“A key feature is that our calculators are relevant to current day rates of cardiovascular disease in different regions of Europe. Importantly, our methods allow them to be easily updated using routinely collected data in the future to ensure they stay relevant as trends in heart and circulatory diseases change.”

This study was carried out by the SCORE2 Working Group and the European Society of Cardiology Cardiovascular Risk Collaboration. It was supported by organisations including the British Heart Foundation, the Medical Research Council, National Institute for Health Research Cambridge Biomedical Research Centre and Health Data Research UK.

Professor Sir Nilesh Samani, Medical Director at the BHF and cardiologist, said: “Heart and circulatory diseases are the world’s biggest killers, impacting the lives of 7.6 million people across the UK alone.

“This new risk tool is a major advance and will save many more people from developing heart attacks, stroke and heart disease, all of which develop silently over many years and strike without warning. It will be the new gold standard for doctors to determine which patients are at the highest risk of these conditions, and enable tailored treatment and lifestyle advice to be given much earlier.”

Reference
SCORE2 risk prediction algorithms: revised models to estimate 10-year risk of cardiovascular disease in Europe. European Heart Journal; 14 June 2021; DOI: 10.1093/eurheartj/ehab309

Adapted from a press release from the British Heart Foundation

A new risk calculator will better predict people at high risk of heart and circulatory diseases years before they strike, and is ready for use across the UK and Europe, according to research published today in the journal European Heart Journal.

cardiovascular disease (CVD)heart attackstrokeriskPublic healthSpotlight on public healthEmanuele Di AngelantonioLisa PennellsBritish Heart FoundationSchool of Clinical MedicineDepartment of Public Health and Primary CareBHF Cambridge Centre for Cardiovascular Research ExcellenceCardiovascular Strategic Research InitiativeThis risk tool... will fit seamlessly into current prevention programmes with substantial real-world impact by improving the prevention of cardiovascular diseases across Europe before they strikeEmanuele Di AngelantonioPexelsMan clutching his heart


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England on track to achieve elimination of HIV transmission by 2030 as model shows sharp decrease in HIV incidence

Thu, 10/06/2021 - 09:20

To manage the HIV epidemic among men who have sex with men (MSM) in England, enhanced testing and earlier treatment strategies were scaled-up between 2011 and 2015 and supplemented from 2015 by pre-exposure prophylaxis (PrEP). The researchers examined the effect of these interventions on the number of new infections and investigated whether the United Nations (UN) targets for HIV control and elimination of HIV transmission by 2030 might be within reach among MSM in England.

A complexity in this assessment is that HIV infections are not observed. Routine surveillance collects data on new HIV diagnoses, but trends in new diagnoses alone can be misleading as they can represent infections that occurred many years previously and depend on the testing behaviour of infected individuals.

To estimate new HIV infections among adult MSM (age 15 years and above) over a 10-year period between 2009 and 2018, the researchers used a novel statistical model that used data on HIV and AIDS diagnoses routinely collected via the national HIV and AIDS Reporting System in England, and knowledge on the progression of HIV. Estimated trends in new infections were then extrapolated to understand the likelihood of achieving the UN elimination target defined as less than one newly acquired infection per 10,000 MSM per year, by 2030.

The peak in the number of new HIV infections in MSM in England is estimated to have occurred between 2012 and 2013, followed by a steep decrease from 2,770 new infections in 2013 to 1,740 in 2015, and a further steadier decrease from 2016, down to 854. The decline was consistent across all age groups but was particularly marked in MSM aged 25–34 years, and slowest in those aged 45 years or older. Importantly, this decrease began before the widespread roll-out of PrEP in 2016, indicating the success of testing and treatment as infection prevention measures among MSM in England.

Through extrapolation, the researchers calculated a 40% likelihood of England reaching the UN elimination target by 2030 and identified relevant age-specific targeting of further prevention efforts (i.e., to MSM aged ≥45 years) to increase this likelihood.

Senior author, Professor Daniela De Angelis, Deputy Director of the MRC Biostatistics Unit, University of Cambridge, said: “This is very good news and suggests that prevention measures adopted in England from 2011 have been effective. With the rollout of PrEP, England looks on course to meet the goal of zero transmissions by 2030. Our study also shows the value of regular estimation of HIV incidence to recognise and respond appropriately to changes in the current downward trend. The challenge now is to achieve these reductions in all groups at risk for HIV acquisition.”

Valerie Delpech, Head of National HIV Surveillance at Public Health England, said: “We have made good progress towards ending HIV transmission by 2030 in England. Frequent HIV testing and the use of PrEP amongst people most at risk of HIV, together with prompt treatment among those diagnosed, are key to ending HIV transmission by 2030. 

“You can benefit from life-saving HIV treatments if you are diagnosed with HIV and it also means you cannot pass the virus on.

“HIV and STI tests are still available through sexual health clinics during the COVID pandemic. Many clinics offer online testing throughout the year – people can order tests on clinic websites, take them in the privacy of their own home, return by post and receive results via text, phone call or post.”

This research is funded by the UK Medical Research Council, UK National Institute of Health Research Health Protection Unit in Behavioural Science and Evaluation, and Public Health England.

Reference
Brizzi, F et al. Tracking elimination of HIV transmission in men who have sex with men in England: a modelling study. Lancet HIV, 10 June 2021; DOI: 10.1016/ S2352-3018(21)00044-8

The annual number of new HIV infections among men who have sex with men in England is likely to have fallen dramatically, from 2,770 in 2013 to 854 in 2018, showing elimination of HIV transmission by 2030 to be within reach – suggests work by researchers from the MRC Biostatistics Unit at the University of Cambridge and Public Health England, published in The Lancet HIV.

Spotlight on public healthPublic healthInfectious diseasesHIV/AIDSDaniela De AngelisPublic Health EnglandMedical Research CouncilSchool of Clinical MedicineMedical Research Council (MRC) Biostatistics UnitThis is very good news and suggests that prevention measures adopted in England from 2011 have been effectiveDaniela De AngelisJason#FreedomTo Know my HIV Status


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People more afraid of catching COVID-19 are more judgemental, study finds

Wed, 09/06/2021 - 00:01

The researchers say their findings are evidence that our morality is shaped by various emotions and intuitions, of which concerns about health and safety are prominent. This means that our judgements of wrongdoing are not completely rational.

The study, published today in the journal Evolutionary Psychology, did not focus on behaviours relating to the pandemic itself - such as social distancing - but considered a wide range of moral transgressions.

Between March and May 2020, over 900 study participants in the USA were presented with a series of scenarios and asked to rate them on a scale from ‘not at all wrong’ to ‘extremely wrong’. This enabled the researchers to measure participants’ responses across five key moral principles: harm, fairness, in-group loyalty, deference to authority, and purity.

Example scenarios include one of loyalty: ‘You see a man leaving his family business to go work for their main competitor’; and one of fairness: ‘You see a tenant bribing a landlord to be the first to get their apartment repainted.’

People who were more worried about catching COVID-19 judged the behaviours in these scenarios to be more wrong than those who were less worried.

“There is no rational reason to be more judgemental of others because you are worrying about getting sick during the pandemic,” said Professor Simone Schnall in the University of Cambridge’s Department of Psychology, senior author of the report.

She added: “These influences on judgements happen outside of our conscious awareness. If we feel that our wellbeing is threatened by the coronavirus, we are also likely to feel more threatened by other people’s wrong-doing – it’s an emotional link.”

The findings contribute to a growing body of evidence of a link between physical disgust – an emotion designed to keep us from harm – and moral condemnation. 

“Disgust is an emotion we think evolved to protect us from harm – avoiding a filthy toilet that might contaminate us with disease, for example. But now we apply it to social situations too, and can feel physically jeopardised by other people’s behaviour,” said Robert Henderson, a PhD student and Gates Scholar in the University of Cambridge’s Department of Psychology and first author of the report.

He added: “The link between being concerned about COVID-19 and moral condemnation is about risks to wellbeing. If you’re more conscious of health risks, you’re also more conscious of social risks – people whose behaviour could inflict harm upon you.”

This research was funded by the Gates Foundation Cambridge and the Bennett Institute for Public Policy.

Reference
Henderson, R.K., & Schnall, S. ‘Disease and Disapproval: COVID-19 Concern is Related to Greater Moral Condemnation.’ Evolutionary Psychology. May 2021. DOI: 10.1177/14747049211021524

Researchers studying how we make moral judgements found that people more concerned about catching COVID-19 were more disapproving of the wrong-doings of others, whatever they were doing wrong.

CoronavirusCOVID-19Simone SchnallRobert HendersonDepartment of PsychologyCambridge Infectious DiseasesJesus CollegeSchool of the Biological SciencesThere is no rational reason to be more judgemental of others because you are worrying about getting sick during the pandemicSimone SchnallCreative Commons Attribution 2.0Legal Gavel


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Scientists can predict which women will have serious pregnancy complications

Tue, 08/06/2021 - 17:01

Nearly all of the organ systems of the mother’s body need to alter their function during pregnancy so that the baby can grow. If the mother’s body cannot properly adapt to the growing baby this leads to major and common issues including fetal growth restriction, fetal over-growth, gestational diabetes, and preeclampsia – a life-threatening high blood pressure in the mother. 

Many of these complications lead to difficult labours for women with more medical intervention and lifelong issues for the baby including diabetes, heart issues and obesity. 

Pregnancy disorders affect around one in ten pregnant women, but current methods to diagnose them are not sensitive or reliable enough to identify all at-risk pregnancies.

Now scientists have found a way to test hormone levels in the placenta to predict which women will have serious pregnancy complications. Their study is published today in the journal Nature Communications Biology

“We found that hormonal biomarkers from the placenta could indicate which women would have pregnancy complications,” said Dr Amanda Sferruzzi-Perri in the University of Cambridge’s Department of Physiology, Development and Neuroscience, who led the study.

She added: “We found that these hormonal biomarkers are present from the first trimester of pregnancy. This is a highly important finding given that pregnancy disorders affect around one in ten pregnant women and are often diagnosed too late, when the complications are already wreaking havoc on the mother’s body and the fetal development.”

Using mouse models, researchers looked at the proteins made by the placenta and compared them to blood samples from women who had uneventful pregnancies and those who developed gestational diabetes. The team developed new methods to isolate and study the endocrine cells in the mouse placenta because these cells are responsible for secreting hormones during pregnancy. 

They profiled the placenta to identify the hormones that are secreted to create a comprehensive map of proteins in the mysterious organ. The mouse model map of hormonal proteins from the placenta was then compared with datasets from studies of the human placenta and pregnancy outcomes and researchers discovered a lot of biological overlap. 

Dr Sferruzzi-Perri said: “We found that around a third of the proteins we identified changed in women during pregnancies with disorders. Using a small study to test if these placental proteins will have some clinical value, we also discovered that abnormal levels of hormones were present in the mother’s blood as early as the first trimester – week 12 of gestation – in women who developed gestational diabetes, a pregnancy complication usually diagnosed at 24-28 weeks. 

“We also identified several specific transcription factors – proteins within the cell that turn on or off genes – that are likely to govern the production of placental hormones which have important implications for understanding how we may improve pregnancy outcomes.”

The scientists explored whether these genetic biomarkers were detectable during pregnancy and used a study that tracked pregnancy outcomes in women at Addenbrooke’s Hospital in Cambridge. They found that blood samples showed these biomarkers in early pregnancy which could lead to earlier diagnosis of complications allowing treatment to begin more quickly.

Dr Claire Meek, a diabetes in pregnancy physician and researcher at Addenbrooke’s, said: “This pregnancy-induced form of diabetes causes accelerated growth of the baby and complications at the time of delivery. Unfortunately, some women already have signs of a big baby at the time of diagnosis at 28 weeks. This new test might be able to identify gestational diabetes earlier in pregnancy, providing opportunities to prevent the disease, or to protect mums and babies from the most harmful complications.” 

Dr Sferruzzi-Perri said: “This work provides new hope that a better understanding of the placenta will result in safer, healthier pregnancies for mothers and babies. Our team is now working to assess whether these discoveries could improve clinical care in future, either through earlier diagnosis or to provide new opportunities to treat these pregnancy complications by targeting the placenta.”

The placenta is a complex biological organ. It forms and grows from the fertilised egg, and attaches to the wall of the uterus. It allows nutrients and oxygen to flow from mother to baby, and removes fetal waste products. Despite its importance, the placenta is a very misunderstood organ and is notoriously difficult to study in pregnant women. But its ability to function properly is vital as it impacts on pregnancy outcomes and the lifelong health of mother and child.

The placenta develops during pregnancy and connects the developing baby to the mother. It serves as the lungs, kidneys, gut and liver for growing babies and carries oxygen and nutrients to the fetus whilst secreting hormones and discarding waste.

Reference

Napso, T. et al. Placental secretome characterization identified candidates for pregnancy complications. Nature Communications Biology, June 2021. DOI: https://doi.org/10.1038/s42003-021-02214-x

Adapted from a press release by St John's College, Cambridge

 

Women who will develop potentially life-threatening disorders during pregnancy can be identified early when hormone levels in the placenta are tested, a new study has shown.

ReproductionAmanda Sferruzzi-PerriTina NapsoAddenbrooke's HospitalDepartment of Physiology, Development and Neuroscience (PDN)Cambridge Reproduction Strategic Research InitiativeSt John's CollegeSchool of the Biological SciencesThis work provides new hope that a better understanding of the placenta will result in safer, healthier pregnancies for mothers and babies.Amanda Sferruzzi-Perri Fishman64 at Shutterstock.comPregnancy scan


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.text-edit-colour-swatch.Theme-ForegroundColor-16,.text-edit-dropdown-colour.Theme-BackgroundColor-16,.text-edit-dropdown-colour.Theme-ForegroundColor-16{background:#c5dfb4}.Theme-BackgroundColor-16{background-color:#c5dfb4}.Theme-BackgroundColor-17{background-color:transparent}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-17,.text-edit-dropdown-colour.Theme-BackgroundColor-17{background:0 0} /*-->*/ " + "ipt>"); } })(navigator, 'userAgent', 'appVersion', 'script', document); //--> */ TwitterFacebook How mass testing helped limit the spread of COVID-19 at the University of Cambridge

Innovative approach shows how higher education institutions can re-open safely

A combination of testing programmes for staff and students, infection control measures and genomic surveillance helped reduce the number of cases of COVID-19 at the University of Cambridge and keep the wider community safe.

At the start of autumn term in October 2020, the University of Cambridge introduced a free weekly asymptomatic screening programme for all students living in College accommodation. It is complemented by a testing programme for staff and students with symptoms of possible COVID-19. Both programmes use PCR testing – still considered the gold standard.

Professor Stephen Toope, Vice-Chancellor of the University of Cambridge, said: “In just eight weeks, a dedicated team at the University set up, from scratch, an innovative programme which, at its peak, was testing around 10,000 students a week. This was an incredible achievement."

Together with staff at our University and Colleges, those colleagues have all worked tirelessly to help us keep our students, staff and the wider Cambridge community safe. I’m truly grateful to them and to every student who has taken part in the programme over the past academic year.Professor Stephen Toope, Vice-Chancellor

Cambridge researchers have released back-to-back studies examining the role of the screening programme, together with other infection control measures, in managing SARS-CoV-2 infections at the University. The results have been made available before peer-review, to allow rapid sharing of information that may be helpful for other universities, as well as mass testing programmes in different settings.

Patrick Maxwell, Regius Professor of Physic at the University of Cambridge, said: “University students are at particular risk of transmitting coronavirus because they live in shared accommodation, and often socialise in large networks. We know that it is possible to spread the disease without showing symptoms. Our team has shown that pooled asymptomatic screening is feasible and effective, and combined with infection control measures make it possible to keep the number of infections very low.”

PhD student Nordin Ćatić swabbing for SARS-CoV-2 infection. (Credit: Dominic Hall)

PhD student Nordin Ćatić swabbing for SARS-CoV-2 infection. (Credit: Dominic Hall)

Asymptomatic screening for COVID-19 helps control transmission

During autumn term 2020, 12,781 students living in College accommodation participated in the University’s Asymptomatic COVID-19 Screening Programme. Students were initially screened every fortnight, but by week seven all participating students were offered screening every week. More than four out of five (82%) of all eligible students ultimately agreed to take part.

Participating students swabbed their noses and throats, then pooled their swabs in the same sample tube as other students from the same household. Pooled samples were analysed at the Cambridge COVID-19 Testing Centre, a collaboration between the University, AstraZeneca and Charles River Laboratories. Pooling swabs made the programme much more efficient, without losing test sensitivity. Over the study period, 50,376 swabs were screened, using only 16,945 tests.

There was no evidence that relying on voluntary participation, or using nose and throat swabs, was a barrier to students taking part. In fact, in a separate survey of more than 750 participants, over 95% of respondents were satisfied with the screening programme and thought that it had made an overall positive contribution to the Cambridge community.

Among 671 students diagnosed with SARS-CoV-2 infection over the study period (5% of participants), 299 (45%) were either identified or pre-emptively asked to self-isolate because of the screening programme. Using a model based on transmission at the University, the researchers estimated that weekly screening reduced the ‘R number’ – the average number of people an individual would infect in a susceptible population – by about a third.

Dr Nicholas Matheson, from the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), designed the screening programme. He said: “By combining regular asymptomatic screening with readily accessible symptomatic testing, we were able to detect almost all cases of SARS-CoV-2 infection amongst students living in our Colleges.

“We hope our screening programme will serve as a useful example for other universities and colleges looking at ways to keep their students, staff and communities safe. We’ve shown that it’s possible to do this at scale by pooling samples, making it logistically and economically viable, without compromising test performance.

“Most importantly, we’ve provided real-world evidence that regular, voluntary asymptomatic screening can be effective in helping control COVID-19 transmission. With the current uncertainty around new variants of concern, and most young adults in the UK – let alone the world – not yet vaccinated, that’s an important lesson about mass testing in general, not just in universities.”

Poster for University of Cambridge asymptomatic screening programme

Poster for University of Cambridge asymptomatic screening programme

Genomic sequencing confirms effectiveness of infection control measures

The University of Cambridge plays a leading role in the COVID-19 Genomics UK (COG-UK) consortium, which sequences the genetic code of viruses isolated from infected individuals to help understand the spread of infection. By analysing these sequences, it is possible to plot a ‘family tree’ (known as phylogenetic tree) of viral isolates and, coupled with epidemiological information, determine whether cases are related.

During autumn term, COG-UK analysed 446 genomes from the University’s testing programmes. Because these programmes use PCR-testing, all positives samples were readily available for sequencing.

The team found that the great majority of transmission chains were short, suggesting that infection control measures implemented by the University, including asymptomatic screening, support for self-isolation and in-house contact tracing, were successful in controlling transmission. In fact, 70% of all University cases belonged to one genetic cluster, likely dispersed by attending a nightclub.

Transmission mainly occurred within student accommodation and/or between students on the same courses. There was minimal evidence of transmission in University departments, or between students and staff. Critically, there was little evidence of transmission between the University and the local community.

Dr Ben Warne, also from CITIID, said: “There are several takeaways from our findings. First, we need to be cautious about access to certain types of high-risk venues during a pandemic, particularly in the context of a young, susceptible student population.

“Second, spread of the virus through the University has been effectively contained using a combination of prompt case identification, including asymptomatic screening, and simple infection control measures, such as supporting affected students and their contacts to isolate.”

Asymptomatic screening programme kit (Credit: Nordin Ćatić)

Asymptomatic screening programme kit (Credit: Nordin Ćatić)

Dr Dinesh Aggarwal, from the Department of Medicine, added: “The lack of evidence of overspill from the University to the community was reassuring and suggests that, with appropriate precautions, it can be possible to keep universities and colleges open safely during the pandemic.

Through COG-UK, the UK has been at the forefront of using genomic epidemiology to inform outbreak investigations. With the widespread availability of sequencing, we believe it is a critical part of public health surveillance required to understand SARS-CoV-2 transmission and biology, and will be a critical part of future pandemic preparedness.Dr Dinesh Aggarwal For more information on how the Asymptomatic COVID-19 Screening Programme was set up and run, see ‘Safety Screens: How COVID-19 testing is helping keep Cambridge students - and the wider local population – safe’. References

Warne, B, et al. Feasibility and efficacy of mass testing for SARS-CoV-2 in a UK university using swab pooling and PCR

Aggarwal, D, et al. Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

TopBuilt with Shorthand Summary: 

A combination of testing programmes for staff and students, infection control measures and genomic surveillance helped reduce the number of cases of COVID-19 at the University and keep the wider community safe.

Image: Affiliation (schools and institutions): School of Clinical MedicineCambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)Department of MedicineCOVID-19 Genomics UK (COG-UK) ConsortiumPeople (our academics and staff): Nicholas MathesonBen WarneDinesh AggarwalPatrick MaxwellSubject (including Spotlight on ... where applicable): COVID-19CoronavirusstudentstestingSection: ResearchNews type: Features

Many of us could carry up to 17kg of fat due to a change in a single gene

Thu, 27/05/2021 - 16:00

The study led by scientists at the MRC Metabolic Diseases Unit which is part of the Wellcome-MRC Institute of Metabolic Science at the University of Cambridge and the MRC Integrated Epidemiology Unit at the University of Bristol is published today in Nature Medicine.

It has been known for a long time that obesity tends to run in families, but it was not until about 20 years ago that scientists started to discover that changes in specific genes can have very large effects on our weight even from early childhood.

One of these genes, the Melanocortin 4 Receptor (MC4R), makes a protein that is produced in the brain where it sends signals to our appetite centres, telling them how much fat we have stored. When the MC4R gene does not work properly, our brains think we have lower fat stores than we do, signalling that we are starving and need to eat.

The research team found that around one in every 340 people may carry a disruptive mutation at MC4R. People who carry these mutations were more likely to have a greater weight from early childhood and, by 18 years of age, they were on average 17 kg (37 lbs or 2.5 stone) heavier, with the majority of this excess weight likely to be fat.

These results were found by studying the MC4R gene in a random sample of around 6,000 participants born in Bristol in 1990-91, who were recruited to Children of the 90s, a health study based at the University of Bristol. This is a unique UK study that recruited approximately 80 percent of the births occurring in a specific region of the South West and which has continued to follow participants. As the Children of the 90s study managed to recruit such a high percentage of mothers during pregnancy, it is one of the most representative and comprehensive studies of its kind.

The authors examined the MC4R gene in all 6,000 people and, whenever a mutation was found, went on to study its functional effects in the laboratory. This meticulous approach has provided the best estimates so far of the frequency and impact of MC4R mutations on people’s weight and body fat. Based on the frequency of mutations in this study, it is possible that around 200,000 people in the UK could carry a substantial amount of additional fat because of mutations in MC4R.

Professor Sir Stephen O’Rahilly, from the University of Cambridge and one of the authors of the study, said: “Parents of obese children are often blamed for poor parenting and not all children obtain appropriate professional help. Our findings show that weight gain in childhood due to a single gene disorder is not uncommon. This should encourage a more compassionate and rational approach to overweight children and their families – including genetic analysis in all seriously obese children.”

Dr Kaitlin Wade, from the University of Bristol’s MRC Integrated Epidemiology Unit and an author on the paper, added: “Work like this is really made possible as a result of the amazing properties presented by a study like Children of the 90s. Having biological samples for sequencing and rich life course data within a representative population sample is critical to allow new understanding and deep characterisation of important biological genetic effects like these.”

Professor Nic Timpson, Children of the 90s' Principal Investigator, and also one of the study’s authors, explained: “This work helps to recalibrate our understanding of the frequency and functional impact of rare MC4R mutations and will help to shape the future management of this important health factor – we extend our thanks to the participants of the Children of the 90s.”

Though the MC4R gene is a striking example, this is only one gene of many that affect our weight and there are likely to be further examples that emerge as genetic sequencing becomes more common.

In the longer term, knowledge of the brain pathways controlled by MC4R should help in the design of drugs that bypass the signalling blockade and help restore people to a healthy weight.

Reference
Wade KH et al. Loss-of-function mutations in the melanocortin 4 receptor in a UK birth cohort. Nature Medicine; 27 May 2021

Adapted from a press release by the Wellcome-MRC Institute of Metabolic Science at the University of Cambridge and the University of Bristol

New research has found that one in every 340 people might carry a mutation in a single gene that makes them more likely to have a greater weight from early childhood and, by 18 years of age, they could be up to 30 pounds heavier with the excess weight likely to be mostly fat. 

Spotlight on public healthPublic healthObesitygeneticsgeneDNAtype 2 diabetesSteve O'RahillyMedical Research CouncilUniversity of BristolAvon Longitudinal Study of Parents and Children (ALSPAC)School of Clinical MedicineMetabolic Research LaboratoriesWellcome-MRC Institute of Metabolic ScienceSchool of the Physical SciencesOur findings show that weight gain in childhood due to a single gene disorder is not uncommon. This should encourage a more compassionate and rational approach to overweight children and their familiesStephen O'RahillymojzagrebinfoWeighing scales and tape measure


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Dive bombing Killer flies are so fast they lose steering control

Thu, 27/05/2021 - 09:20

These are the findings of a study by researchers at the Universities of Cambridge, Lincoln, and Minnesota, published in the Journal of the Royal Society Interface

Killer flies (Coenosia attenuata) perform high-speed aerial dives to attack prey flying beneath them, reaching impressive accelerations of up to 36 m/s2, equivalent to 3.6 times the acceleration due to gravity (or 3.6g). This happens because they beat their wings as they fall, combining the acceleration of powered flight with the acceleration of gravity.

This is an impressive feat: diving Falcons, the fastest animals that predate in the air, achieve much lower accelerations of only 6.8m/s2. Falcons dive by folding their wings and simply letting gravity accelerate them towards their prey.

For the tiny Killer fly though, the high speeds achieved in aerial dives could come as a surprise - because the researchers think the fly doesn’t take the effect of gravity into account when diving to intercept a target. 

To get their results, the researchers built a transparent ‘flight arena’ and flew a dummy prey target through it at constant velocity. Killer flies were filmed with high speed video cameras as they attacked the target, and the researchers watched the footage back in slow motion - using this data to reconstruct the entire attack sequence in 3D. 

The study found that Killer flies reached much higher accelerations in flight when taking off from the ceiling of the arena, compared to from the floor or walls. The flies beat their wings at a similar rate wherever they launched from, indicating that their flight speed is determined by a combination of wing power and gravity. 

“When Killer flies took off from the floor or walls of the arena, they moved at the time when they could take the shortest path to the target. But they couldn’t manage that when they took off from the ceiling because the high acceleration caused by gravity changed the expected flight path,” said Sergio Rossoni, a PhD student in the University of Cambridge’s Department of Zoology and first author of the paper.

By diving with super-high acceleration the Killer fly sometimes catches its target prey extremely quickly, but it often misses because its speed makes it challenging to change course mid-dive if the prey moves. But even if the fly doesn’t land on target, the dive quickly reduces its distance from the prey so it can keep sight of it while making the final manoeuvers to catch it.

The researchers think the effect of not accounting for gravity during downward dives might be compensated by another advantage. High speed dives force the potential prey to change direction as the attacker approaches, but to do this the prey has to slow down - making it easier to catch.
Insects that hunt in the air usually attack their prey upwards, because the contrast of the prey against the sky makes it easier to see. Killer flies are unusual insect predators in this respect; hunting downwards against a visually cluttered ground, using eyes that have only coarse resolution, is more difficult. 

“This research into miniature flies helps us understand what shortcuts are acceptable when survival depends on fast decisions and accurate actions, but the sensory capabilities and processing power of the predator are heavily constrained,” said Professor Gonzalez-Bellido at the University of Minnesota, who led the study.

This research was funded by the Air Force Office of Scientific Research, the Biotechnology and Biological Sciences Research Council and the Royal Society.

Reference
Rossoni, S. et al: ‘Gravity and active acceleration limit the ability of killer flies (Coenosia attenuate) to steer towards prey when attacking from above.’ J.R.Soc.Interface, May 2021. DOI: 10.1098/rsif.2021.0058

 

Killer flies can reach accelerations of over 3g when aerial diving to catch their prey – but at such high speeds they often miss because they can’t correct their course.

Sergio RossoniUniversity of MinnesotaUniversity of LincolnDepartment of ZoologyMuseum of ZoologySchool of the Biological SciencesThe high acceleration caused by gravity changed the flies' expected flight path when they took off from the ceilingSergio RossoniS.T.FabianKiller fly


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Switching off heart protein could protect against heart failure

Thu, 27/05/2021 - 08:42

There is an unmet need to find drugs that can successfully improve the heart’s ability to pump blood efficiently after it’s been damaged following a heart attack. However, many drugs that make failing heart muscle contract more strongly have been deemed unsafe, leaving a huge gap in heart attack and heart failure treatment. Scientists now believe that they might have identified a new drug target – a protein called MARK4.

In research funded by the British Heart Foundation (BHF), Cambridge scientists found levels of MARK4 were elevated in mouse hearts after a heart attack. When they compared mice with and without MARK4 in the heart, they found hearts without the protein were 57 per cent better at pumping blood. This protective effect was seen 24 hours after a heart attack and lasted for the entire follow-up period of four weeks.

The team identified for the first time that MARK4 fine-tunes a structural network within the heart muscle cell – called the microtubule network – that attaches to the machinery which makes heart muscle cells contract and relax. When MARK4 levels were increased after a heart attack, microtubules were tightly anchored onto the contractile machinery in the heart, causing more resistance and preventing them from functioning normally. When MARK4 levels were reduced, microtubules were loosely anchored, making it easier for the heart to contract and relax.

After a heart attack, in the heart muscle cells of mice without MARK4, the speed of contraction increased by 42 per cent and the speed of relaxation increased by 47 per cent, compared to muscle cells from mice with the MARK4 protein. They were also close to functioning at the same level as healthy heart muscle cells, showing the power of lowering levels of MARK4.

Now, the researchers suggest that drugs to switch off MARK4 could provide a promising new way to improve recovery and help the heart to pump blood more efficiently in people with failing hearts.

Dr Xuan Li, BHF Intermediate Research Fellow at University of Cambridge BHF Centre of Research Excellence, said: “After years of research we’ve revealed an entirely new and promising way that could help the recovery of failing hearts.

“It’s early days, and we now need to test the longer-term effects of switching off MARK4. But if drugs to do that prove successful, the life-changing benefits could be seen in people with other types of heart disease as well as those who’ve had a heart attack and developed heart failure.”

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation, said: “Heart attacks are a major cause of disability worldwide - people who’ve had a major heart attack are at much greater risk of developing chronic heart failure. There are around 920,000 people living with heart failure in the UK, and we desperately need drugs to drastically improve the heart’s function in these patients.

“These findings are a positive step forward. Further research is needed to refine and test drugs that can target MARK4 before we’ll see them given to people who’ve had a heart attack and develop heart failure.”

This study was also supported by the Isaac Newton Trust, Wellcome, Cancer Research UK and the German Research Foundation.

Reference
Yu, X et al. MARK4 controls ischaemic heart failure through microtubule detyrosination. Nature; 26 May 2021; DOI: 10.1038/s41586-021-03573-5

Adapted from a press release by the British Heart Foundation.

Switching off a heart muscle protein could provide a new way for drugs to combat heart failure in people who’ve had a heart attack, according to research led by the University of Cambridge and published in the journal Nature.

heart diseasecardiovascular disease (CVD)Xuan LiBritish Heart FoundationSchool of Clinical MedicineDepartment of MedicineBHF Cambridge Centre for Cardiovascular Research ExcellenceCardiovascular Strategic Research InitiativeAfter years of research we’ve revealed an entirely new and promising way that could help the recovery of failing heartsXuan LigeraltHeart graphic


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Heal thyself

Mon, 24/05/2021 - 14:28
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Academic and industry researchers are looking for new ways to treat neurodegeneration by recycling bad proteins.  

Three companies, Astex Pharmaceuticals, Eisai Ltd and Eli Lilly and Company, are joining forces with research scientists across Cambridge to explore promising new approaches to the treatment of neurodegenerative disease.

When unwanted material builds up in our cells, our bodies generally take care of it using a process known as autophagy - which literally translates as ‘self-eating’. 

Autophagy is normally carefully controlled so that it removes damaged proteins and keeps cells healthy. One feature of neurodegenerative diseases such as Alzheimer’s and Parkinson’s is that damaged proteins build up in the brain — ultimately destroying nerve cells. What if we could get rid of these proteins by switching on the body’s own mechanism for clearing out its cellular trash? Could this lead to breakthrough treatments for these devastating conditions?

That is the challenge a group of research scientists and industry partners in Cambridge has set itself, in a groundbreaking model of pre-competitive collaboration led by the University’s Milner Therapeutics Institute.

The Milner Institute’s Deputy Director, Dr Kathryn Chapman, explains the rationale for setting up this new Consortium project: “Finding new treatments for neurodegeneration is a mammoth challenge. Everyone recognises it to be a vitally important target for drug discovery, but it is such a complex area that it is hard for companies to make significant progress on their own.”

Dr Kathryn Chapman, Milner Therapeutics Institute

Dr Kathryn Chapman, Milner Therapeutics Institute

Chapman and colleagues felt that the Milner Institute could play an important convening role, bringing together academic and industry experts to make real progress in translating the basic science into a better understanding of the different kinds of therapeutic interventions that might be possible - and effective.

Getting the right people in the room 

The approach is all about bringing the right people, know-how and experience together. In this case, that meant not only experts from different companies but also research scientists from different institutions across Cambridge.

One of these is world authority on autophagy, Dr Nicholas Ktistakis from the Babraham Institute. "The pathway is already well understood," he explains. “It has been studied for many years in terms of the basic science but whether it can be mobilised to treat disease, that’s more of an open question - and one that we are trying to answer together."

Dr Nicholas Ktistakis, Babraham Institute

Dr Nicholas Ktistakis, Babraham Institute

Working alongside Ktistakis is Dr Alex Whitworth from the MRC-Mitochondrial Biology Unit in the University’s School of Clinical Medicine. Whitworth is an expert in mitophagy, a form of autophagy affecting mitochondria, which plays a critical role in cellular life and death.

Expertise in early-stage drug discovery and target validation for dementia is provided by the third research partner, the ALBORADA Drug Discovery Institute, part of the Alzheimer’s Research UK Drug Discovery Alliance, also based in the School of Clinical Medicine. Its involvement in the consortium is led by Chief Scientific Officer, Dr John Skidmore, who is hugely supportive of the collaboration: "Clearly, autophagy is an area of great therapeutic interest in which everyone is asking more or less the same questions. It seems ideally suited to this kind of collaborative approach."

Dr John Skidmore, ALBORADA Drug Discovery Institute

Dr John Skidmore, ALBORADA Drug Discovery Institute

When Alzheimer’s Research UK established the Drug Discovery Alliance it did so with collaborative intent. The Alliance's Director of Research, Dr Susan Kohlhaas sees real benefits to a model where universities, corporations and charity work together: “The ALBORADA Drug Discovery Institute puts industry experts in an academic setting, with their work made possible by the charitable ALBORADA Trust."

"By uniting expertise, we can help get treatments to people with dementia sooner. For more than a million people in the UK living with a neurodegenerative disease, this can’t be soon enough." Dr Susan Kohlhaas, Director of Research, Alzheimer’s Research UK Drug Discovery Alliance

For Ktistakis at the Babraham Institute, one of the major benefits of the collaborative model is in being able to reproduce results. "A huge problem in drug discovery efforts," he explains, "is that often when someone discovers something, no-one else is able to replicate their findings. Here we have three different labs, all bringing very specific expertise to the problem, making sure we are talking to each other at every step of the way, checking that we can see what the other labs are seeing.”

In partnership with industry

The other critical dimension of this collaboration is the involvement of three pharmaceutical companies: Astex, Eisai and Eli Lilly and Company. These companies all bring deep knowledge from their own research programmes in neurodegeneration.

Peter Atkinson, Head of External Innovation, Neurology Business Group at Eisai, explained why they were so keen to be involved: “Companies have been trying to harness endogenous clearance pathways for years but it’s a very complex area. There are so many different ways in which you can modulate the pathway.

"Because autophagy takes place throughout the whole body, you need to be sure that if you switch it on to correct something in the brain, you don’t inadvertently cause problems elsewhere.”

“What we like about this approach is that by sharing knowledge and resources, we are de-risking the effort and harnessing both academic expertise and robust, industry-standard evaluation and validation processes.”

Nicola Wallis, Senior Vice President Biology at Astex Pharmaceuticals agrees: “This is a really interesting development for us. We have worked with the Milner Institute before but not with other pharma companies. The difference with this initiative is that we can all use the results and explore individual areas on our own going forward. As companies, we will be more interested in some areas than others. So this is very much a win, win.”

Dr Nicola Wallis, Astex Pharmaceuticals

Dr Nicola Wallis, Astex Pharmaceuticals

Research Advisor at Eli Lilly and Company, Fiona Menzies, is excited to see the data that is generated from this collaboration, confident "that it will deliver unique insights into this important area of biology that would not be achieved by any one of us working alone."

The role of the Milner Therapeutics Institute

It all started in 2019, when the Milner Institute organised a ‘sandpit’ to which researchers and companies were invited to brainstorm around the broad topic of neurodegeneration. Jeremy Carmichael, Senior Vice President, Corporate Development, at Astex described how “the sandpit really struck a chord with people. It was an exciting topic which immediately got real traction.”

This was echoed by Chapman who could see the potential for a collaborative approach: “The group quickly became more than the sum of its parts. The power of all these different minds working on the same problem was spectacular.”

Having created a huge amount of interest with the sandpit, Chapman and team were determined to capitalise on the obvious appetite for collaboration. However, creating a consortium of organisations that don't usually work together is not a task for the fainthearted.

For Eisai's Peter Atkinson, the Milner Institute's role has been critical in getting the project off the ground, through its tireless efforts to "broker the relationships, broker the science and broker the contracts.”

"It deserves huge credit," agrees Menzies, "for identifying the need for enhanced collaboration in this area, and then, not only taking the initiative to bring together a diverse group of interested parties but ultimately making this project happen." 

Where next?

Over the next two years, the aim is to make real progress in understanding the molecular pathways controlling autophagy and which of the possible treatment targets have the most potential. "Our hope," says Chapman, "is that some new targets for drug discovery can be taken forward into clinical development by one or more of the companies."

Meanwhile the Milner Therapeutics Institute plans to build on this success and set up multi-company projects with other partners in the Consortium, which now includes 10 pharma companies. It has recently issued a call for more ideas for collaboration between researchers and industry, in a wide range of disease areas including cancer, neuroscience and infectious diseases.

"We can see the power of collaboration," says Chapman, "and want to apply it to other areas where there are opportunities to make real progress in developing new treatments."

Find out more about how Cambridge works with its life sciences partners here. TopBuilt with Shorthand Summary: 

Three companies, Astex Pharmaceuticals, Eisai Ltd and Eli Lilly and Company, are joining forces with research scientists across Cambridge to explore promising new approaches to the treatment of neurodegenerative disease.

Image: Affiliation (schools and institutions): Milner Therapeutics InstituteSchool of Clinical MedicineMedical Research Council (MRC) Mitochondrial Biology UnitExternal Affiliations: Babraham InstitutePeople (our academics and staff): Kathryn ChapmanNicholas KtistakisSubject (including Spotlight on ... where applicable): businessdrug discoverypartnershipSpotlight on neuroscienceFuture therapeuticsspotlight on future therapeuticsspotlight on the future of medicineSection: ResearchNews type: Features

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.text-edit-colour-swatch.Theme-ForegroundColor-16,.text-edit-dropdown-colour.Theme-BackgroundColor-16,.text-edit-dropdown-colour.Theme-ForegroundColor-16{background:#c5dfb4}.Theme-BackgroundColor-16{background-color:#c5dfb4}.Theme-BackgroundColor-17{background-color:transparent}.text-edit-colour-value .text-edit-colour-swatch.Theme-BackgroundColor-17,.text-edit-dropdown-colour.Theme-BackgroundColor-17{background:0 0} /*-->*/ " + "ipt>"); } })(navigator, 'userAgent', 'appVersion', 'script', document); //--> */ TwitterFacebook Could a vaccine protect us against heart attacks?

Professor Ziad Mallat (Credit: Nick Saffell)

Professor Ziad Mallat (Credit: Nick Saffell)

Professor Ziad Mallat and his team have been shortlisted for a £30 million grant from the British Heart Foundation. If successful, atherosclerosis – hardening of the arteries – could become a thing of the past.

Ziad Mallat has a bold ambition: he wants to help create a world free from heart attacks and stroke - and to achieve this, he says, one day we could find ourselves being offered a vaccine to protect us in later life.

With the arrival of COVID-19, vaccines are very much at the forefront of people’s minds. But Mallat is not an opportunist, looking to tap into the zeitgeist – in fact, he first told me about his idea when we met in January 2020, before the newly-emerging SARS-CoV-2 had even been given its name.

Mallat is a professor of cardiovascular medicine at Cambridge and is interested in one of the major causes of heart and circulatory disease, namely atherosclerosis. Atherosclerosis is the hardening and narrowing of the vessels that carry blood to and from the heart. It is caused by the build-up of abnormal material called plaques – collections of fat, cholesterol, calcium and other substances circulating in the blood.

This causes two problems. The first is that the blood vessels narrow, restricting blood flow. Think of it like a motorway – when all three lanes are open, traffic can move freely, but as soon as one – or worse, two – of the lanes are closed for roadworks, traffic becomes congested and slows down. The second – potentially lethal – problem is when fragments of the plaques break off, blocking blood flow entirely, cutting off vital supplies to the brain and leading to stroke.

How build up of lipids (fat) in the artery prevents blood from flowing (Credit: Oregon State University)

How build up of lipids (fat) in the artery prevents blood from flowing (Credit: Oregon State University)

At its root, atherosclerosis is a disease of the immune system, says Mallat – a disease of chronic inflammation. “When these fatty deposits enter the artery wall, they induce an injury,” he explains. “The body sees itself as being under attack and the immune system responds, sending immune cells to the artery. The initial goal is to clear the aggressor and repair the blood vessel.”

The problem is that the immune response can become too aggressive, causing collateral damage to the arteries. “You can compare it to COVID – it’s not the coronavirus that kills us, it’s our overactive immune systems.”

Yet, despite atherosclerosis being widely recognised as a chronic inflammatory disease, he says, there are currently no anti-inflammatory drugs to treat the disease. Clinical trials of promising drugs have either failed to show benefit or have highlighted harmful side effects. Instead, people at risk are offered blood-thinning drugs and statins to reduce cholesterol, neither of which get to the root cause.

“At the moment, most of the information we have on the role of the immune system in atherosclerosis is what we know from pre-clinical models,” he says, referring to studies in cells and animals. “We don’t understand the human disease very well. We don’t know the precise pathways that are involved.”

Mallat hopes to change this. He and his team are one of four finalists shortlisted for the Big Beat Challenge – a global competition organised by the British Heart Foundation (BHF). At stake is a research award of up to £30 million ‘for the world’s greatest minds to tackle the world’s biggest killers’. Mallat’s proposal is iMAP – a project aimed at creating fundamental new knowledge about the link between the immune defence system and atherosclerosis.

iMAP is an ambitious project that would, he says, be “transformational” in our understanding of – and ability to treat – atherosclerosis. He has assembled a team of world leading scientists from different disciplines – medicine, biology, immunology, genetics, mathematics, and even vaccine development – that will harness the very latest technologies, including artificial intelligence and machine learning, to create the world's first 3D map of these plaques. This map will enable them to explore each individual cell, looking at its position, its genetic material, how it communicates with other cells and how its role changes over time, for example.

When I first met Mallat, he described this as akin to a ‘Google Map’ of atherosclerosis, but in fact, as he explains it now, this doesn’t give it justice – it will be far more detailed, and a map in time, as well as space.

“It’s the difference between looking at the Earth from a satellite and being able to examine a street, and going to each house and knocking on the door and asking what each person is doing and who they are talking to.” Ziad Mallat

Video courtesy of Dr Helle Jorgensen (Division of Cardiovascular Medicine, University of Cambridge)

Video courtesy of Dr Helle Jorgensen (Division of Cardiovascular Medicine, University of Cambridge)

All of this, he believes, will help his team identify the key components that are involved in triggering the inflammatory response. Once they have identified some potential drug targets, they aim to leverage further funding and support from spinout and pharmaceutical companies to develop new anti-inflammatory drugs. Even more excitingly, he says, it could help them develop a vaccine against the disease.

“We want to identify the [atherosclerosis] equivalent of the spike protein,” he says, referring to the component of the coronavirus that is the target of the Oxford University/AstraZeneca vaccine and other vaccines against COVID-19.

Such a vaccine would prime the immune system so that it recognises the ‘injured’ arteries and does not mount a full-on assault.

“We need to stop thinking of atherosclerosis as a disease of the elderly,” he says, pointing out that it can affect younger people – women who have the autoimmune condition lupus, for example, are at higher risk – but regardless, the seeds of the condition are sown long before people develop the condition. “You need an intervention early on, to stop the disease from happening in the first place.”

For now, Mallat is focused on developing their proposal – their pitch – further to put his team in the best possible position to secure the funding. They have been speaking to patient groups to get their input into the questions they should be asking and are inviting members of the public to provide feedback. He is keen to engage the public in their work, partly, he says, because he wants people to better understand what the condition is and how as individuals they can reduce their risk of developing it.

“We believe we can make atherosclerosis a disease of the past and fulfil our vision of a world free from the fear of heart attacks and strokes. We want to show the BHF that we have the most compelling proposal to win the funding and help us deliver that promise.”Ziad Mallat Please show your support for iMap by sharing @Cambridgecardio's tweet:

I would choose #HeartAttackVaccine as @TheBHF's #BigBeatChallenge winner! Which would you pick?

— CambridgeCardio (@Cambridgecardio) April 15, 2021

Published 20 May 2021

TopBuilt with Shorthand Summary: 

Professor Ziad Mallat and his team have been shortlisted for a £30 million grant from the British Heart Foundation. If successful, atherosclerosis – hardening of the arteries – could become a thing of the past.

Image: Affiliation (schools and institutions): School of Clinical MedicineDepartment of MedicineBHF Cambridge Centre for Cardiovascular Research ExcellenceDepartment of Cardiovascular MedicineCardiovascular Strategic Research InitiativeExternal Affiliations: British Heart FoundationPeople (our academics and staff): Ziad MallatSubject (including Spotlight on ... where applicable): spotlight on future therapeuticscardiovascular disease (CVD)atherosclerosisheart attackstrokeheart diseaseSection: ResearchNews type: Features

Cambridge researchers awarded the Millennium Technology Prize

Tue, 18/05/2021 - 15:32

University of Cambridge chemists Shankar Balasubramanian and David Klenerman have been jointly awarded the 2020 Millennium Technology Prize, one of the world’s most prestigious science and technology prizes, by Technology Academy Finland (TAF).

The global prize, awarded at two-year intervals since 2004 to highlight the impact of science and innovation on society, is worth €1 million. Of the nine previous winners of the Millennium Technology Prize, three have subsequently gone on to win a Nobel Prize. This is the first time that the prize has been awarded to more than one recipient for the same innovation, celebrating the significance of collaboration. The announcement of the 2020 award was delayed due to the COVID-19 pandemic. 

Professors Balasubramanian and Klenerman co-invented Solexa-Illumina Next Generation DNA Sequencing (NGS), technology that has enhanced our basic understanding of life, converting biosciences into ‘big science’ by enabling fast, accurate, low-cost and large-scale genome sequencing – the process of determining the complete DNA sequence of an organism’s make-up. They co-founded the company Solexa to make the technology available to the world.

The technology has had – and continues to have – a transformative impact in the fields of genomics, medicine and biology. One measure of the scale of change is that it has allowed a million-fold improvement in speed and cost when compared to the first sequencing of the human genome. In 2000, sequencing of one human genome took over 10 years and cost more than a billion dollars: today, the human genome can be sequenced in a single day at a cost of $1,000. More than a million human genomes are sequenced at scale each year, thanks to the technology co-invented by Professors Balasubramanian and Klenerman, meaning we can understand diseases much better and much more quickly.

Professor Sir Shankar Balsubramanian FRS from the Yusuf Hamied Department of Chemistry, Cancer Research UK Cambridge Institute and a Fellow of Trinity College, said: “I am absolutely delighted at being awarded the Millennium Technology Prize jointly with David Klenerman, but it’s not just for us, I’m happy on behalf of everyone who has contributed to this work.”

Professor Sir David Klenerman FMedSci FRS from the Yusuf Hamied Department of Chemistry, and a Fellow of Christ’s College, said: “It’s the first time that we’ve been internationally recognised for developing this technology. The idea came from Cambridge and was developed in Cambridge. It’s now used all over the world, so I’m delighted largely for the team of people who worked on this project and contributed to its success.”

Next-generation sequencing involves fragmenting sample DNA into many small pieces that are immobilized on the surface of a chip and locally amplified. Each fragment is then decoded on the chip, base-by-base, using fluorescently coloured nucleotides added by an enzyme. By detecting the colour-coded nucleotides incorporated at each position on the chip with a fluorescence detector – and repeating this cycle hundreds of times – it is possible to determine the DNA sequence of each fragment.

The collected data is then analysed using computer software to assemble the full DNA sequence from the sequence of all these fragments. The NGS method’s ability to sequence billions of fragments in a parallel fashion makes the technique fast, accurate and cost-efficient. The invention of NGS was a revolutionary approach to the understanding of the genetic code in all living organisms.

Next-generation sequencing provides an effective way to study and identify new coronavirus strains and other pathogens. With the emergence of the COVID-19 pandemic, the technology is now being used to track and explore mutations in the coronavirus. This work has helped the creation of multiple vaccines now being administered worldwide and is critical to the creation of new vaccines against new dangerous viral strains. The results will also be used to prevent future pandemics.

The technology is also allowing scientists and researchers to identify the underlying factors in individuals that contribute to their immune response to COVID-19. This information is essential to unravelling the reason behind why some people respond much worse to the virus than others.

NGS technology has revolutionised global biological and biomedical research and has enabled the development of a broad range of related technologies, applications and innovations. Due to its efficiency, NGS is widely adopted in healthcare and diagnostics, such as cancer, rare diseases, infectious medicine, and sequencing-based non-invasive prenatal testing.

It is increasingly used to define the genetic risk genes for patients with a rare disease and to define new drug targets for disease in defined patient groups. NGS has also contributed to the creation of new and powerful biological therapies like antibodies and gene therapies.

In the field of cancer, NGS is becoming the standard analytical method for defining personalised therapeutic treatment. The technology has dramatically improved our understanding of the genetic basis of many cancers and is often used both for clinical tests for early detection and diagnostics both from tumours and patients’ blood samples.

In addition to medical applications, NGS has also had a major impact on all of biology as it allows the clear identification of thousands of organisms in almost any kind of sample, which is important for agriculture, ecology and biodiversity research.

Academy Professor Päivi Törmä, Chair of the Millennium Technology Prize Selection Committee, said: “The future potential of NGS is enormous and the exploitation of the technology is still in its infancy. The technology will be a crucial element in promoting sustainable development through personalisation of medicine, understanding and fighting killer diseases, and hence improving the quality of life. Professor Balasubramanian and Professor Klenerman are worthy winners of the prize.”

Professor Marja Makarow, Chair of Technology Academy Finland said: “Collaboration is an essential part of ensuring positive change for the future. Next Generation Sequencing is the perfect example of what can be achieved through teamwork and individuals from different scientific backgrounds coming together to solve a problem.

“The technology pioneered by Professor Balasubramanian and Professor Klenerman has also played a key role in helping discover the coronavirus’s sequence, which in turn enabled the creation of the vaccines – itself a triumph for cross-border collaboration – and helped identify new variants of COVID-19.”

Tomorrow (19 May 2021) Professors Balasubramanian and Klenerman will deliver the Millennium Technology Prize Lecture, talking about their innovation, at 14:30 at the Millennium Innovation Forum. The lecture can be accessed here.

British duo Professor Shankar Balasubramanian and Professor David Klenerman have been awarded the Millennium Technology Prize for their development of revolutionary DNA sequencing techniques.

genome sequencingGenomicsDNAImpactspin-outCancerShankar BalasubramanianDavid KlenermanMillennium Technology PrizeIlluminaYusuf Hamied Department of ChemistryCancer Research UK Cambridge InstituteSchool of the Physical SciencesSchool of Clinical MedicineTrinity CollegeChrist's CollegeFitzwilliam College Journeys of Discovery: Rapid genome sequencing University of CambridgeShankar Balasubramanian and David Klenerman


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Mothers can influence offspring’s height, lifespan and disease risk in unexpected ways – through their mitochondria

Mon, 17/05/2021 - 16:00

The study, published today in Nature Genetics, found that genetic variants in the DNA of mitochondria could increase the risk of developing these conditions, as well influencing characteristics such as height and lifespan.

There was also evidence that some changes in mitochondrial DNA were more common in people with Scottish, Welsh or Northumbrian genetic ancestry, implying that mitochondrial DNA and nuclear DNA (which accounts for 99.9% of our genetic make-up) interact with each other.

Almost all of the DNA that makes up the human genome – the body’s ‘blueprint’ – is contained within the nuclei of our cells. Among other functions, nuclear DNA codes for the characteristics that make us individual as well as for the proteins that do most of the work in our bodies.

Our cells also contain mitochondria, often referred to as ‘batteries’, which provide the energy for our cells to function. They do this by converting the food that we eat into ATP, a molecule capable of releasing energy very quickly. Each of these mitochondria is coded for by a tiny amount of ‘mitochondrial DNA’. Mitochondrial DNA makes up only 0.1% of the overall human genome and is passed down exclusively from mother to child.

While errors in mitochondrial DNA can lead to so-called mitochondrial diseases, which can be severely disabling, until now there had been little evidence that these variants can influence more common diseases. Several small-scale studies have hinted at this possibility, but scientists have been unable to replicate their findings.

Now, a team at the University of Cambridge has developed a new technique to study mitochondrial DNA and its relation to human diseases and characteristics in samples taken from 358,000 volunteers as part of UK Biobank, a large-scale biomedical database and research resource.

Dr Joanna Howson, who carried out the work while at the Department of Public Health and Primary Care at the University of Cambridge, said: “Using this new method, we've been able to look for associations between the numerous features that have been recorded for participants of UK Biobank and see whether any correlate with mitochondrial DNA.

“Aside from mitochondrial diseases, we don’t generally associate mitochondrial DNA variants with common diseases. But what we’ve shown is that mitochondrial DNA – which we inherit from our mother – influences the risk of some diseases such as type 2 diabetes and MS as well as a number of common characteristics.”

Among those factors found to be influenced by mitochondrial DNA are: type 2 diabetes, multiple sclerosis, liver and kidney function, blood count parameters, life span and height. While some of the effects are seen more extremely in patients with rare inherited mitochondrial diseases – for example, patients with severe disease are often shorter than average – the effect in healthy individuals tends to be much subtler, likely accounting for just a few millimetres’ height difference, for example.

There are several possible explanations for how mitochondrial DNA exerts its influence. One is that changes to mitochondrial DNA lead to subtle differences in our ability to produce energy. However, it is likely to be more complicated, affecting complex biological pathways inside our bodies – the signals that allow our cells to operate in a coordinated fashion.

Professor Patrick Chinnery from the MRC Mitochondrial Biology Unit at Cambridge said: “If you want a complete picture of common diseases, then clearly you’re going to need to factor in the influence of mitochondrial DNA. The ultimate aim of studies of our DNA is to understand the mechanisms that underlie these diseases and find new ways to treat them. Our work could help identify potential new drug targets.”

Regional variations in mitochondrial DNA suggest complex interaction with nuclear DNA

Unlike nuclear DNA, which is passed down from both the mother and the father, mitochondria DNA is inherited exclusively from the mother. This suggests that the two systems are inherited independently and hence there should be no association between an individual’s nuclear and mitochondrial DNA – however, this was not what the team found.

The researchers showed that certain nuclear genetic backgrounds are associated preferentially with certain mitochondrial genetic backgrounds, particularly in Scotland, Wales and Northumbria. This suggests that our nuclear and mitochondrial genomes have evolved – and continue to evolve – side-by-side and interact with each other.

One reason that may explain this is the need for compatibility. ATP is produced by a group of proteins inside the mitochondria, called the respiratory chain. There are over 100 components of the respiratory chain, 13 of which are coded for by mitochondrial DNA; the remainder are coded for by nuclear DNA. Even though proteins in the respiratory chain are being produced by two different genomes, the proteins need to physically interlock like pieces of a jigsaw.

If the mitochondrial DNA inherited by a child was not compatible with the nuclear DNA inherited from the father, the jigsaw would not fit together properly, thereby affecting the respiratory chain and, consequently, energy production. This might subtly influence an individual’s health or physiology, which over time could be disadvantageous from an evolutionary perspective. Conversely, matches would be encouraged by evolution and therefore become more common.

This could have implications for the success of mitochondrial transfer therapy – a new technique that enables scientists to replace a mother’s defective mitochondria with those from a donor, thereby preventing her child from having a potentially life-threatening mitochondrial disease.

“It looks like our mitochondrial DNA is matched to our nuclear DNA to some extent – in other words, you can’t just swap the mitochondria with any donor, just as you can’t take a blood transfusion from anyone,” explained Professor Chinnery. “Fortunately, this possibility has already been factored into the approach taken by the team at Newcastle who have pioneered this therapy.”

The study was funded by Wellcome and the British Heart Foundation. Additional support was provided by the NIHR Cambridge Biomedical Research Centre.

Reference
Yonova-Doing, E et al. An atlas of mitochondrial DNA genotype-phenotype associations in the UK Biobank. Nature Genetics; 17 May 2021; DOI: 10.1038/s41588-021-00868-1

Mitochondria -  the ‘batteries’ that power our cells – play an unexpected role in common diseases such as type 2 diabetes and multiple sclerosis, concludes a study of over 350,000 people conducted by the University of Cambridge.

Spotlight on neuroscienceNeurosciencegeneticsGenomicsPatrick ChinneryJoanna HowsonWellcomeBritish Heart FoundationNIHR Cambridge Biomedical Research CentreSchool of Clinical MedicineDepartment of Clinical NeurosciencesMedical Research Council (MRC) Mitochondrial Biology UnitDepartment of Public Health and Primary CareIf you want a complete picture of common diseases, then clearly you’re going to need to factor in the influence of mitochondrial DNAPatrick ChinneryBruno NascimentoMother and child


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‘Pre-bunk’ tactics reduce public susceptibility to COVID-19 conspiracies and falsehoods, study finds

Wed, 12/05/2021 - 10:18

A short online game designed to fight conspiracies about COVID-19 boosts people’s confidence in detecting misinformation by increasing their ability to perceive its “manipulativeness” compared to genuine news, according to a study.  

Go Viral!, developed by the University of Cambridge’s Social Decision-Making Lab in partnership with the UK Cabinet Office and media agency DROG, was launched last autumn as part of the UK government’s efforts to tackle coronavirus falsehoods circulating online.

The five-minute game puts people in the shoes of a purveyor of fake pandemic news, encouraging players to create panic by spreading misinformation about COVID-19 using social media – all within the confines of the game.

Researchers say that, by giving people this taste of the techniques used to disseminate fake news, it acts as an inoculant: building a psychological resistance against malicious falsehoods by raising awareness of how misinformation works.

“While fact-checking is vital work, it can come too late. Trying to debunk misinformation after it spreads is often a difficult if not impossible task,” said Prof Sander van der Linden, Director of the Social Decision-Making Lab at Cambridge University.

“Go Viral! is part of a new wave of interventions that aim to ‘pre-bunk’. By preemptively exposing people to a microdose of the methods used to disseminate fake news, we can help them identify and ignore it in the future.”

The latest findings on the game’s effectiveness, published in the journal Big Data and Society, are accompanied by research on another COVID-19 “prebunking” intervention used by the United Nations Educational, Scientific and Cultural Organization (UNESCO).

UNESCO deployed infographics across social media highlighting tropes common to COVID conspiracy theories, such as claims of a “secret plot” or that the virus was spread intentionally, as part of their #ThinkBeforeSharing campaign.

“By exposing people to the methods used to produce fake news we can help create a general ‘inoculation’, rather than trying to counter each specific falsehood,” said study lead author and Cambridge Gates Scholar Melisa Basol.

The Cambridge researchers found the UNESCO approach also proved effective, albeit with a smaller effect size than the proactive game.  

The Go Viral! project began with seed funding from Cambridge University’s COVID-19 rapid response fund, and was then supported and backed by the UK Cabinet Office and promoted by the World Health Organisation and UN.

The game has now been played over 400,000 times in a variety of languages – including Italian, Spanish, Ukrainian, and Brazilian Portuguese – since its October launch.

Players try and gain “likes” by promoting noxious posts on COVID-19, harnessing propaganda techniques such as fraudulent expertise and the use of emotionally charged language to stoke outrage and fear.

The final stage sees players “go viral” when they push a baseless conspiracy theory that explodes online and ignites nationwide protests.

For the new study, researchers used a sample of 3,548 players over the age of 18, including native speakers of three languages in which the game is available: English, German and French.

Study participants were shown 18 social media posts – nine containing information from credible news sources, and high-quality versions of COVID-19 conspiracies making up the rest – and asked the extent to which they felt manipulated by the framing and content of each one. 

Roughly a third of the study participants then played Go Viral!, while another third – a control group – played Tetris for the same amount of time, and the final group read UNESCO’s set of “prebunking” infographics. Lastly, everyone was given the same set of news items to rate, a mixture of real and fake.

Just over half (55%) the Tetris players got better at spotting the falsehoods, little better than chance – suggesting many were guessing.

However, 74% of the “pre-bunked” Go Viral! players got much better at sensing when they were being manipulated by the misinformation: a 19 percentage point increase over the control group.

The infographics generated a more modest but still useful six percentage point increase in manipulation detection compared to the control (61% vs 55%).

When it came to confidence in their ability to spot fake news going forward, only 50% of the Tetris players said it had increased – no better than chance – whereas 67% of Go Viral! players felt they were less likely to get duped in the future. 

In a follow-up survey one week after the single play of the game, participants were asked to rate a further set of real and fake social media posts about COVID-19. Go Viral! players were still rating COVID-19 misinformation as significantly more manipulative, while the effects of the UNESCO infographics had faded.

“Both interventions are fast, effective and easily scalable, with the potential to reach millions of people around the world,” said Dr Jon Roozenbeek, study co-lead author from Cambridge’s Department of Psychology. 

“Interestingly, our findings also show that the active inoculation of playing the game may have more longevity than passive inoculations such as reading the infographics.”

“COVID-19 falsehoods and conspiracies pose a real threat to vaccination programmes in almost every nation. Every weapon in our arsenal should be used to fight the fake news that poses a threat to herd immunity. Pre-bunking initiatives have a crucial role to play in that global fight,” Roozenbeek said.

Stefania Giannini, Assistant Director-General for Education at UNESCO, added: “Cambridge University has provided solid backing for 'pre-bunking' misinformation and conspiracy theories propagated and reinforced during the pandemic, which have real-life consequences undermining trust in science and fueling hate speech.

“In this context, UNESCO’s work in education and media and information literacy is even more critical to strengthen learners’ digital citizenship.”

Latest research on digital interventions deployed by UK government and UNESCO suggests that exposing people to a “microdose” of techniques used by misinformation merchants helps “inoculate” them against fake news about the pandemic.

COVID-19social psychologyfake newsdigital skillsSander van der LindenJon RoozenbeekMelisa BasolDepartment of PsychologySchool of the Biological SciencesCambridge University has provided solid backing for 'pre-bunking' misinformation and conspiracy theories propagated and reinforced during the pandemicStefania Giannini, Assistant Director-General for Education at UNESCOScreen shots of Go Viral! on the left, and an example of UNESCO's #ThinkBeforeSharing campaign on the right.


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Nature has enormous potential to fight climate change and biodiversity loss in the UK - report

Wed, 12/05/2021 - 00:01

Incorporating contributions from over 100 experts across academia, statutory agencies and NGOs, the comprehensive evaluation of the available evidence details the strengths, limitations and trade-offs of nature-based solutions in different UK habitats. 

Professor Jane Memmott, President of the British Ecological Society, said: “The Nature-based Solutions report offers a real basis for setting effective policies and incentives that will maximise the benefits of nature-based solutions in the UK for the climate and biodiversity.” 

The report finds that nature-based solutions can provide a valuable contribution to climate change mitigation and can simultaneously protect and enhance biodiversity, improve human wellbeing, bring economic benefit, and provide a wide range of ecosystem services. 

Despite the huge range of benefits nature-based solutions have, the report makes clear that they should be seen as complementary to other climate and conservation actions, not as a replacement to them. 

Restoration of the UK’s peatlands is a priority nature-based solution identified in the report. The UK’s 2.6 million hectares of peatland contain around 3 billion tonnes of carbon, but most are in a degraded state and are no longer actively sequestering carbon. Estimates suggest that they could be emitting the equivalent of 23 million tonnes of carbon dioxide annually, approximately half the amount released through the nation’s agricultural sector. 

Restoring degraded peatlands through rewetting and revegetation can reduce and eventually halt these emissions as well as bring benefits in terms of biodiversity conservation and flood protection. 

Restoring UK woodlands can also make a significant impact as a nature-based solution. Forests cover 13% of the UK and the report finds there is scope to expand this significantly to sequester more carbon, although the full benefits will not be felt before 2050. Reducing flood risk, providing shade and cooling, and biodiversity benefits from native woodland expansion are also highlighted as positive outcomes from woodlands as a nature-based solution.

Professor David Coomes at the University of Cambridge, lead author of the Woodlands chapter of the report, said: “For large-scale tree planting to be effective in capturing carbon, we will need to avoid species-rich grasslands, peat and other organic soils. Our focus should be on areas of low-quality grassland. However, this will reduce the UK’s capacity to produce meat and dairy, meaning a shift in our diets would be needed to avoid importing more of these products and offshoring our carbon footprint elsewhere.”

Marine environments that surround the UK can also offer significant nature-based solutions thanks to the large size of habitats. Saltmarshes and seagrasses are important carbon sinks, and their restoration can contribute to climate mitigation. Saltmarshes also provide coastal protection from sea-level rise and storms and provide high-biodiversity coastal habitats, especially for bird species. 

Professor Rick Stafford at Bournemouth University and lead author of the Marine Chapter said: “In marine environments nature-based solutions changes are nearly always win-win. Investment in nature-based solutions that restore or protect coastal environments is an effective mechanism of achieving greater biodiversity, protection from storms and carbon capture with few trade-offs.” 

The implementation of nature-based solutions to help achieve net-zero commitments and tackle biodiversity loss will require shared knowledge, resources, and effective partnerships across different policy areas.

Long-term policies, goals and government commitments will be necessary to support long-term investment, research and monitoring of the solutions. 

Although some habitats are highlighted as priorities, the report emphasises that all habitats covered can deliver nature-based solutions and play a role in addressing the climate and biodiversity crises.

Adapted from a press release by the British Ecological Society.

 

The full report can be downloaded here: Nature-based Solutions for Climate Change in the UK: A Report by the British Ecological Society. 

The virtual launch event takes place from 10:00-11:30 on Wednesday, 12 May, hosted by Rt Hon Philip Dunne MP, Chair of the Environment Audit Committee of the House of Commons, and presented by broadcaster and journalist Tom Heap. It can be watched here.

 

 

A report launched today by the British Ecological Society, with contributions from the University of Cambridge, offers the first complete assessment of the potential of nature-based solutions to mitigate climate change and benefit biodiversity in the UK. 

Sustainable EarthDavid CoomesBritish Ecological SocietyDepartment of Plant SciencesUniversity of Cambridge Conservation Research Institute (UCCRI)Fitzwilliam CollegeSchool of the Biological SciencesFor large-scale tree planting to be effective in capturing carbon...our focus should be on areas of low-quality grasslandDavid Coomes Trees against blue sky


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The Academy of Medical Sciences announces election of new Fellows 2021

Tue, 11/05/2021 - 12:39

The Academy of Medical Sciences has elected 50 prominent biomedical and health scientists to its respected and influential Fellowship. The new Fellows have been selected for their exceptional contributions to the advancement of medical science through innovative research discoveries and translating scientific developments into benefits for patients and the wider society.

Professor Dame Anne Johnson, President of the Academy of Medical Sciences, said: “I am truly delighted to welcome these 50 new Fellows to the Academy’s Fellowship, and I offer my congratulations to each of them on their exceptional contribution to biomedical and health science. The knowledge, skill and influence that each brings to the Fellowship is the Academy’s most powerful asset.

“The last year has clearly demonstrated the power and prowess of UK biomedical science, and I am proud of how many Fellows, new and old, have been at the forefront of the COVID-19 response in the UK and globally.

“Although it is hard to look beyond the pandemic right now, I want to stress how important it is that the Academy Fellowship represents the widest diversity of biomedical and health sciences. The greatest health advances rely on the findings of many types of research, and on multidisciplinary teams and cross-sector and global collaboration.”

Professor Franklin Aigbirhio FRSC

Professor of Molecular Imaging Chemistry, Department of Clinical Neurosciences and the Department of Chemistry, Senior Research Fellow, Magdalene College

Professor Aigbirhio’s research focuses on the development and application of new biomedical imaging technologies for clinical research in areas such as dementia, acute brain injury and hypertension. His research seeks to enable earlier detection and a greater understanding of the disorders, thereby aiding the development of new treatments. A further objective of Professor Aigbirhio’s work is to enable these new imaging technologies to be more accessible and widely applied throughout the NHS.

“It’s a pleasure and honour to be elected to this Fellowship, which I recognise is an outcome of the collaborations with many talented colleagues at Cambridge and further afield, for which I give my sincere thanks,” said Aigbirhio.

“Going forward my election to the Fellowship provides a platform to highlight the role of black researchers and participants in biomedical and health research and to increase their involvement.”

Professor Ravindra Gupta

Professor of Clinical Microbiology at the Cambridge Institute of Therapeutic Immunology and Infectious Diseases, Fellow, Homerton College

Professor Gupta has worked extensively in HIV, both at molecular and population levels, and his work demonstrating escalating global resistance led to change in WHO treatment guidelines for HIV. He led the team that demonstrated HIV cure in the ‘London Patient’ – only the second in history.

In 2020 he was named as one of the 100 most influential people worldwide by TIME Magazine. Gupta deployed his expertise in RNA virus genetics and biology during the COVID-19 pandemic to report the first evidence for immune escape of SARS-CoV-2 within an individual, defining the process by which new variants likely arise, and also reporting the first data on Pfizer BioNTech vaccine-induced antibody responses against the B.1.1.7 ‘Kent UK’ variant.

“I am honoured to have been elected to Fellowship of the Academy of Medical Sciences,” said Gupta. “The COVID-19 pandemic has demonstrated the importance of cross-disciplinary science. Research excellence across medical sciences and translation to health improvements has been at the centre of the Academy’s mission and I am very pleased to now be able to contribute to fulfilling this aim as a fellow.”

Professor Brian Huntly

Head of the Department of Haematology and Professor of Leukaemia Stem Cell Biology

Professor Huntly’s research focuses on the stem cell aspects of the evolution of haematological malignancies, in particular acute myeloid leukaemia and lymphoma. His election recognises his many contributions to the understanding and treatment of blood cancers.

“I am delighted and honoured to be elected to the Fellowship of the Academy of Medical Sciences,” said Huntly. “The Academy’s aims of bringing the best minds in biomedical research together, supporting talent, asking challenging questions and sharing our work so that all can benefit from it mirror very much our own aims here in Cambridge. Biomedical research is a hugely collaborative endeavour and I see my election as recognition of the hard work of many people who have contributed to my research and also highlighting the tremendous work we are doing at the University of Cambridge Department of Haematology.”

Professor Adrian Liston

Senior Group Leader, Babraham Institute, Senior Research Fellow, Churchill College

Professor Adrian Liston works in the field of immunology, based around the question of the biological checkpoints that restrain immune activation. His research investigates the basis for pathological immune activation in the contexts of autoimmune diseases, primary immunodeficiencies and neuroinflammation. By understanding the genetic, molecular and cellular basis of immune checkpoint failure in these conditions, the rationale selection of therapeutics can help prevent or treat pathologies.

“This is a really wonderful recognition of the work from my team”, Liston said. “I’ve been lucky to work with an outstanding team of scientists, able to work on immune pathology from different angles – from the clinic or the lab, as an immunologist or a neuroscientist, in advanced techniques ranging from cytometry through to computational modelling. The curiosity and interdisciplinarity of the team are what has let us explore new fields and push the boundaries forwards.”

Professor Benjamin Simons FRS

Royal Society EP Abraham Professor, Department of Applied Mathematics and Theoretical Physics and Senior Group Leader of the Gurdon Institute, Fellow, St John's College

As a theorist, Professor Simons has contributed to a diverse range of fields, from quantum condensed matter physics to developmental and cancer biology. His research translates concepts and approaches from statistical physics to gain predictive insights in the collective dynamics of complex systems. In biology, his studies have revealed common mechanisms of stem cell regulation, and how these programmes become subverted during the early phase of tumour growth.

Simons said: “As a theorist, and relative newcomer to the field of biomedical sciences, it is a great honour to be elected as a Fellow of the Academy of Medical Sciences.”

Cambridge scientists are among the new Fellows announced today by the Academy of Medical Sciences.

Professor Franklin AigbirhioProfessor Ravindra GuptaProfessor Brian HuntlyProfessor Adrian ListonProfessor Benjamin SimonsBabraham InstituteDepartment of Clinical NeurosciencesDepartment of ChemistryCambridge Institute of Therapeutic Immunology and Infectious DiseasesDepartment of HaematologyDepartment of Applied Mathematics and Theoretical PhysicsGurdon InstituteSchool of Clinical MedicineSchool of the Physical SciencesThe greatest health advances rely on the findings of many types of research, and on multidisciplinary teams and cross-sector and global collaboration.Professor Dame Anne Johnson, President of the Academy of Medical Sciences


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Unhealthy patterns of diet, exercise, and sleep linked to high risk of cardiovascular disease in autistic people

Mon, 10/05/2021 - 16:34

The results are published today in the journal Molecular Autism.

Earlier research suggests that autistic people die 16-35 years younger than expected, and that greater health problems may contribute to this risk. The present study is the first to consider the diet, exercise, and sleep patterns of autistic adults and how these patterns may relate to health outcomes.

The team at the Autism Research Centre in Cambridge developed an anonymous, online survey about lifestyle choices and daily habits, personal medical history, and family medical history. The final study included 1,183 autistic adults and 1,203 non-autistic adults aged 16-90 years.

The results showed that autistic adults were far less likely than non-autistic adults to meet very minimal health recommendations for diet, exercise, and sleep. Autistic adults were also far more likely to have atypical eating patterns (including limited diet) and sleep disturbance. They were more likely to be underweight or obese than non-autistic individuals.

These poor lifestyle habits were associated with greater risk of cardiovascular conditions such as high blood pressure, heart disease, and stroke among autistic males, and this was a stronger association even than a family history of a cardiovascular condition. Though it is not possible to say conclusively that a poorer lifestyle led to cardiovascular problems, the findings provide the first indication that promoting healthy choices regarding diet, exercise, and sleep may help to reduce the excess risks of health conditions in autistic adults. 

While the results indicate that there may be other biological or environmental factors that leave autistic individuals at greater risk of health conditions, they also provide a clear target for intervention. Difficulties with maintaining a healthy lifestyle may also have knock-on effects beyond physical health, including limiting opportunities for social interaction (which may centre around mealtimes or exercise), and could contribute to worsening mental health, and affect employment or education.

The lead researcher of the study, Elizabeth Weir, a PhD student at the Autism Research Centre in Cambridge, said: “These findings help us to better understand the experiences of autistic adults, and have wider implications for quality of life. We need to understand the reasons for restricted diet, limited exercise, and lack of sleep, to provide better support. This may include programmes for health education, and additional mental health support or supported living and working schemes.”

Dr Carrie Allison, Director of Research Strategy at the Autism Research Centre and a member of the research team, said: “The challenges we see among autistic children regarding lifestyle behaviours extend into adulthood. Given the implications for risk of chronic disease and length of life, it is critical that we work to identify effective strategies for supporting health choices by autistic people of all ages.”

Professor Simon Baron-Cohen, Director of the Autism Research Centre and a member of the team, said: “The wider picture suggests that autistic adults experience vulnerability in a variety of contexts, and this is just one new area that we should consider. Seeing that autistic adults are having such a hard time comparatively with healthy lifestyle habits has clear healthcare and policy implications: we need to create new and better support systems tailored to the specific needs of autistic people.”

Reference
Weir, E.,  et al. An investigation of the diet, exercise, sleep, BMI, and health outcomes of autistic adults. Molecular Autism 12, 31 (2021). DOI: 10.1186/s13229-021-00441-x

Funding
Funding for this project was generously provided by the Autism Research Trust, the Rosetrees Trust, and the Cambridge and Peterborough NHS Foundation Trust, the Corbin Charitable Trust, the MRC, the Wellcome Trust and the Innovative Medicines Initiative.

Autistic people have far greater risks of long term physical health conditions than others, but the reasons for this remain unclear. New research from the University of Cambridge suggests that unhealthy lifestyle habits may be an important contributing factor. 

Spotlight on neuroscienceNeuroscienceautismcardiovascular disease (CVD)dietheart diseaseexerciseElizabeth WeirSimon Baron-CohenCarrie AllisonAutism Research TrustRosetrees TrustCambridge and Peterborough NHS Foundation TrustCorbin Charitable TrustWellcomeMedical Research CouncilInnovative Medicines InitiativeSchool of Clinical MedicineDepartment of PsychiatryAutism Research CentreThese findings help us to better understand the experiences of autistic adults, and have wider implications for quality of life. We need to understand the reasons for restricted diet, limited exercise, and lack of sleep, to provide better supportElizabeth WeirPeter BurdonTiles spelling "autism"


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