̽��ֱ�� of Cambridge - US National Institutes of Health

Inside the mind of a young person

cjb250 — Thu, 15 Nov 2018 17:18:17 +0000

Study clears important hurdle towards developing an HIV vaccine

cjb250 — Wed, 13 Sep 2017 07:03:22 +0000

In a study published in 2009, results from a clinical trial carried out in Thailand found that an experimental vaccine against HIV lowered the rate of human infection by 31%. This gave cautious optimism that a vaccine against the virus might be a feasible prospect. A vaccine has obvious advantages over treatment with anti-retroviral drugs in that prevention could lead to eradication.

However, one of the major problems that prevented the vaccine from generating long-lasting protection was that the key immune response it needed to generate was very short-lived. ̽��ֱ��reason has now become clear and researchers have found a potential solution.

When a virus enters the body, its aim is to get into our cells and replicate itself again and again, spreading throughout the body. HIV is especially notorious because a protein on its outer coat specifically targets CD4 T-helper cells, the master regulators of the immune system. These cells produce important signals for other types of immune cell: B-cells, which make antibodies; and T-killer cells, which kill virus-infected cells.

By specifically targeting the CD4 T-helper cells, HIV cripples the command and control centre of the immune system and prevents immune defences from working effectively. HIV does not even need to enter and kill the CD4 T-cells – it can cause a functional paralysis of these cells simply by binding its gp140 with the CD4 receptor, an important molecule on the surface of T-helper cells.

HIV’s envelope proteins are a key component of vaccines to protect against HIV infection. ̽��ֱ��body’s immune system targets this protein and generates antibodies directed at HIV’s outer coat to prevent the virus from entering the cells. If the effects of the vaccine last long enough, then with the assistance of robust helper T-cells, the human body should be able to develop antibodies that neutralise a large variety of HIV strains and protect people from infection.

Previous studies showed that vaccinating using a form of the outer coat protein called gp140 leads to the triggering of B-cells which produce antibodies to the virus, but only for a brief period and insufficient to generate sufficient antibodies that are protective from HIV infection over a long period.

Working with scientists in the UK, France, the USA, and the Netherlands, Professor Jonathan Heeney from the Laboratory of Viral Zoonotics at the ̽��ֱ�� of Cambridge recognised that the binding of gp140 to the CD4 receptor on T-helper cells was probably causing this block, and that by preventing gp140 attaching to the CD4 receptor, the short-term block in antibody producing B-cells could be overcome.

In two back-to-back studies published in the print edition of Journal of Virology, the research team has demonstrated for the first time that this approach works, providing the desired responses that were capable of lasting over a year.

“For a vaccine to work, its effects need to be long lasting,” says Professor Heeney. “It isn’t practical to require people to come back every 6-12 months to be vaccinated. We wanted to develop a vaccine to overcome this block and generate these long-lived antibody producing cells. We have now found a way to do this.”

̽��ֱ��study showed that the addition of a tiny specific protein patch to the gp140 protein dramatically improved B-cell responses by blocking binding to the CD4 receptor and hence preventing the paralysis of T-helper cells early in the key stages of the immune response – like preventing a key from getting stuck in a lock. This small patch was one of several strategies to improve gp140 for an HIV vaccine by a team led by Susan Barnett (now at the Bill and Melinda Gates Foundation).

This modified vaccine approach now better stimulates long-lasting B-cell responses, boosting the ability of B-cells to recognise different contours of the virus coat and to make better antibodies against it. This new finding will allow HIV vaccines to be developed that give the immune system enough time to develop the essential B-cell responses to make protective antibodies.

“B-cells need time to make highly effective neutralising antibodies, but in previous studies B-cell responses were so short lived they disappeared before they have the time to make all the changes necessary to create the ‘silver bullets’ to stop HIV,” adds Professor Heeney.

“What we have found is a way to greatly improve B-cell responses to an HIV vaccine. We hope our discovery will unlock the paralysis in the field of HIV vaccine research and enable us to move forward.”

̽��ֱ��team now hopes to secure funding to test their vaccine candidate in humans in the near future.

̽��ֱ��studies were funded by the National Institutes of Health, USA, and the Isaac Newton Trust Cambridge.

Reference

Bogers, WMJM, et al. Increased, Durable B-Cell and ADCC Responses Associated with T-Helper Cell Responses to HIV-1 Envelope in Macaques Vaccinated with gp140 Occluded at the CD4 Receptor Binding Site. Journal of Virology; DOI: 10.1128/JVI.00811-17.

Shen, X et al. Cross-Linking of a CD4-Mimetic Miniprotein with HIV-1 Env gp140 Alters Kinetics and Specificities of Antibody Responses against HIV-1 Env in Macaques. Journal of Virology; DOI: 10.1128/JVI.00401-17.

An international team of researchers has demonstrated a way of overcoming one of the major stumbling blocks that has prevented the development of a vaccine against HIV: the ability to generate immune cells that stay in circulation long enough to respond to and stop virus infection.

For a vaccine to work, its effects need to be long lasting. It isn’t practical to require people to come back every 6-12 months to be vaccinated

Jonathan Heeney

NIAID

3D print of HIV (edited)

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Leprosy turns the immune system against itself, study finds

cjb250 — Wed, 23 Aug 2017 08:33:57 +0000

Leprosy is an infectious disease that affects the skin and peripheral nerves and is caused by Mycobacterium leprae and, less commonly, Mycobacterium lepromatosis. According to the World Health Organization, there has been a dramatic decrease in the global disease burden in the past few decades: from 5.2 million people with leprosy in 1985 to 176,176 at the end of 2015.

Despite the disease having been known about for thousands of years – many people will have first heard about it through references in the Bible – very little is understood about its biology. This is in part because the bacteria are difficult to grow in culture and there are no good animal models: M. leprae can grow in the footpads of mice, but do not cause nerve damage; the disease causes nerve damage in armadillos, but these animals are rarely used in research.

Now, an international team led by researchers at the ̽��ֱ�� of Cambridge, UK, and the ̽��ֱ�� of Washington, the ̽��ֱ�� of California Los Angeles and Harvard ̽��ֱ��, USA, have used a new animal model, the zebrafish, to show for the first time how M. leprae damage nerves by infiltrating the very cells that are meant to protect us. Zebrafish are already used to study another species of mycobacteria, to help understand tuberculosis (TB).

Scientists have previously shown that the nerve damage in leprosy is caused by a stripping away of the protective insulation, the myelin sheath, that protects nerve fibres, but it was thought that this process occurred because the bacteria got inside Schwann cells, specialist cells that produce myelin.

In new research published today in the journal Cell, researchers used zebrafish that had been genetically modified so that their myelin is fluorescent green; young zebrafish are themselves transparent, and so the researchers could more easily observe what was happening to the nerve cells. When they injected bacteria close to the nerve cells of the zebrafish, they observed that the bacteria settled on the nerve, developing donut-like ‘bubbles’ of myelin that had dissociated from the myelin sheath.

When they examined these bubbles more closely, they found that they were caused by M. leprae bacteria inside of macrophages – literally ‘big eaters’, immune cells that consume and destroy foreign bodies and unwanted material within the body. But, as is also often the case with TB, the M. leprae was consumed by the macrophages but not destroyed.

“These ‘Pac-Man’-like immune cells swallow the leprosy bacteria, but are not always able to destroy them,” explains Professor Lalita Ramakrishnan from the Department of Medicine at the ̽��ֱ�� of Cambridge, whose lab is within the Medical Research Council’s Laboratory of Molecular Biology. “Instead, the macrophages – which should be moving up and down the nerve fibre repairing damage – slow down and settle in place, destroying the myelin sheath.”

Professor Ramakrishnan working with Dr Cressida Madigan, Professor Alvaro Sagasti, and other colleagues confirmed that this was the case by knocking out the macrophages and showing that when the bacteria sit directly on the nerves, they do not damage the myelin sheath.

̽��ֱ��team further demonstrated how this damage occurs. A molecule known as PGL-1 that sits on the surface of M. leprae ‘reprograms’ the macrophage, causing it to overproduce a potentially destructive form of the chemical nitric oxide that damages mitochondria, the ‘batteries’ that power nerves.

“ ̽��ֱ��leprosy bacteria are, essentially, hijacking an important repair mechanism and causing it to go awry,” says Professor Ramakrishnan. “It then starts spewing out toxic chemicals. Not only does it stop repairing damage, but it creates more damage itself.”

“We know that the immune system can lead to nerve damage – and in particular to the myelin sheath – in other diseases, such as multiple sclerosis and Guillain–Barré syndrome,” says Dr Cressida Madigan from the ̽��ֱ�� of California, Los Angeles. “Our study appears to place leprosy in the same category of these diseases.”

̽��ֱ��researchers say it is too early to say whether this study will lead to new treatments. There are several drugs being tested that inhibit the production of nitric oxide, but, says Professor Ramakrishnan, the key may be to catch the disease at an early enough stage to prevent damage to the nerve cells.

“We need to be thinking about degeneration versus regeneration,” she says. “At the moment, leprosy can be treated by a combination of drugs. While these succeed in killing the bacteria, once the nerve damage has been done, it is currently irreversible. We would like to understand how to change that. In other words, are we able to prevent damage to nerve cells in the first place and can we additionally focus on repairing damaged nerve cells?”

̽��ֱ��research was funded by the National Institutes of Health, the Wellcome Trust, and the AP Giannini Foundation.

Reference
Madigan, CA et al. A Macrophage Response To Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage In Leprosy. Cell; 24 Aug 2017; DOI: 10.1016/j.cell.2017.07.030

Leprosy hijacks our immune system, turning an important repair mechanism into one that causes potentially irreparable damage to our nerve cells, according to new research that uses zebrafish to study the disease. As such, the disease may share common characteristics with conditions such as multiple sclerosis.

̽��ֱ��leprosy bacteria are, essentially, hijacking an important repair mechanism and causing it to go awry

Lalita Ramakrishnan

Wellcome Library, London

Hand showing leprosy

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Zika warnings lead to ‘significant’ increase in demand for abortions in Latin America

cjb250 — Wed, 22 Jun 2016 21:00:51 +0000

However, in many of these countries, abortion is either illegal or highly restricted, leaving pregnant women with few options and potentially driving women to use unsafe methods, access abortion drugs without medical supervision or visit underground providers.

On 17 November 2015, the Pan American Health Organization (PAHO) issued an alert about the Zika virus in Latin America. Although the virus, spread by mosquitos, causes only mild symptoms, it can have serious complications for unborn children, ranging from eye and hearing defects through to microcephaly (abnormally small heads) and other severe fetal brain defects. Following the PAHO alert, several countries issued health advisory warnings, including urging women to avoid pregnancy.

For several years, one option for women seeking an abortion in Latin America has been Women on Web, a non-profit organisation that provides medical abortion outside the formal healthcare setting through online telemedicine, in countries where safe abortion is not universally available. A team of researchers from the US and UK analysed data on requests for abortion through the website between 1 January 2010 and 2 March 2016 in 19 Latin-American countries, assessing whether requests for abortion increased beyond expected trends following the PAHO alert.

̽��ֱ��researchers found that in almost all of the countries that had issued health warnings about Zika and had legal restrictions on abortions, the number of requests for abortion through Women on Web rose significantly – effectively doubling in Brazil, Ecuador and Venezuela, and increasing by over a third in most of the other countries. In countries that had issued no health warnings, there was no statistically-significant increase.

Assistant Professor Abigail Aiken from the ̽��ֱ�� of Texas at Austin, said: “Accurate data on the choices pregnant women make in Latin America is hard to obtain. If anything, our approach may underestimate the impact of health warning on requests for abortion, as many women may have used an unsafe method or visited local underground providers.”

Dr Catherine Aiken from the Department of Obstetrics & Gynaecology at the ̽��ֱ�� of Cambridge added: “ ̽��ֱ��World Health Organization predicts as many as four million Zika cases across the Americas over the next year, and the virus will inevitably spread to other countries. It isn’t enough for health officials just to warn women about the risks associated Zika – they must also make efforts to ensure that women are offered safe, legal, and accessible reproductive choices.”

̽��ֱ��research was supported by the National Institutes of Health and the National Science Foundation.

Reference
Aiken, ARA et al. Requests for Abortion in Latin America in the Wake of Zika Virus. NEJM; 22 June 2016. DOI: 10.1056/NEJMc1605389

Declaration of interests
Rebecca Gomperts is Founder and Director of Women on Web. James Trussell serves on the Advisory Board of Women on Web. Marc Worrell is an IT Consultant for Women on Web.

Health warnings about complications related to Zika virus significantly increased demand for abortions in Latin American countries, according to a new study published today in the New England Journal of Medicine.

It isn’t enough for health officials just to warn women about the risks associated Zika – they must also make efforts to ensure that women are offered safe, legal, and accessible reproductive choices

Catherine Aiken

Pan American Health Organization

Sin Zancudos no hay Zika - Cúcuta

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‘Clogged-up’ immune cells help explain smoking risk for TB

cjb250 — Thu, 24 Mar 2016 16:00:00 +0000

TB is an infectious disease caused by Mycobacterium tuberculosis that primarily infects the lungs, but can also infect other organs. It is transmitted from person to person through the air. ̽��ֱ��disease can cause breathlessness, wasting, and eventual death. While treatments do exist, the drug regimen is one of the longest for any curable disease: a patient will typically need to take medication for six months.

For people exposed to TB, the biggest risk factor for infection is exposure to smoke, including active and passive cigarette smoking and smoke from burning fuels. This risk is even greater than co-infection with HIV. However, until now it has not been clear why smoke should increase this risk.

When TB enters the body, the first line of defence it encounters is a specialist immune cell known as a macrophage (Greek for ‘big eater’). This cell engulfs the bacterium and tries to break it down. In many cases, the macrophage is successful and kills the bacterium, preventing TB infection, but in some cases TB manages not just to avoid destruction, but to use macrophages as ‘taxi cabs’ and get deep into the host, spreading the infection. TB’s next step is to cause infected macrophages to form tightly-organised clusters known as tubercles, or granulomas. Once again here, the macrophages and bacteria fight a battle – if the macrophages lose, the bacteria use their advantage to spread from cell to cell within this structure.

An international team of researchers, led by the ̽��ֱ�� of Cambridge, and the ̽��ֱ�� of Washington, Seattle, studying genetic variants that increase susceptibility to TB in zebrafish – a ‘see-through’ animal model for studying the disease – identified a variant linked to ‘lysosomal deficiency disorders’. ̽��ֱ��lysosome is a key component of macrophages responsible for destroying bacteria. This particular variant caused a deficiency in an enzyme known as cathepsin, which acts within the lysosome like scissors to ‘chop up’ bacteria; however, this would not necessarily explain why the macrophages could not destroy the bacteria, as many additional enzymes could take cathepsin’s place.

̽��ֱ��key, the researchers found, lay in a second property of the macrophage: housekeeping. As well as destroying bacteria, the macrophage also recycles unwanted material from within the body for reuse, and these lysosomal deficiency disorders were preventing this essential operation.

Professor Lalita Ramakrishnan from the Department of Medicine at the ̽��ֱ�� of Cambridge, who led the research, explains: “Macrophages act a bit like vacuum cleaners, hoovering up debris and unwanted material within the body, including the billions of cells that die each day as part of natural turnover. But the defective macrophages are unable to recycle this debris and get clogged up, growing bigger and fatter and less able to move around and clear up other material.

“This can become a problem in TB because once the TB granuloma forms, the host’s best bet is to send in more macrophages at a slow steady pace to help the already infected macrophages.”

Image: Left - normal macrophages (green); Right - dysfunctional macrophages whose lysosomes (red) are clogged with cell debris. Credit: Steven Levitte

“When these distended macrophages can’t move into the TB granuloma,” adds co-author Steven Levitte from the ̽��ֱ�� of Washington, “the infected macrophages that are already in there burst, leaving a ‘soup’ in which the bacteria can grow and spread further, making the infection worse.”

̽��ֱ��researchers looked at whether the effect seen in the lysosomal deficiency disorders, where the clogged-up macrophage could no longer perform its work, would also be observed if the lysosome became clogged up with non-biological material. By ‘infecting’ the zebrafish with microscopic plastic beads, they were able to replicate this effect.

“We saw that accumulation of material inside of macrophages by many different means, both genetic and acquired, led the same result: macrophages that could not respond to infection,” explains co-author Russell Berg.

This discovery then led the team to see whether the same phenomenon occurred in humans. Working with Professor Joe Keane and his colleagues from Trinity College Dublin, the researchers were able to show that the macrophages of smokers were similarly clogged up with smoke particles, helping explain why people exposed to smoke were at a greater risk of TB infection.

“Macrophages are our best shot at getting rid of TB, so if they are slowed down by smoke particles, their ability to fight infection is going to be greatly reduced,” says Professor Keane. “We know that exposure to cigarette smoke or smoke from burning wood and coal, for example, are major risk factors for developing TB, and our finding helps explain why this is the case. ̽��ֱ��good news is that stopping smoking reduces the risk – it allows the impaired macrophages to die away and be replaced by new, agile cells.”

Image: Smoke-clogged macrophages of cigarette smokers are unable to move to engulf infecting TB bacteria, which may explain why cigarette smokers are more susceptible to tuberculosis. Credit: Kevin Takaki and drawn by Paul Margiotta

̽��ֱ��research was supported by the National Institutes of Health, the Wellcome Trust, the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC), the Health Research Board of Ireland and ̽��ֱ��Royal City of Dublin Hospital Trust.

Also contributing to this research were Professor David Tobin from Duke ̽��ֱ��, Dr Cecilia Moens from the Fred Hutchinson Cancer Research Institute, Drs C.J. Cambier and J. Cameron from ̽��ֱ�� of Washington, Dr Kevin Takaki from ̽��ֱ�� of Cambridge and Drs Seonadh O’Leary and Mary O’Sullivan from Trinity College Dublin.

Reference
Berg, RD, Levitte, S et al. Lysosomal Disorders Drive Susceptibility to Tuberculosis by Compromising Macrophage Migration. Cell; 24 Mar 2016; 10.1016/j.cell.2016.02.034

Smoking increases an individual’s risk of developing tuberculosis (TB) – and makes the infection worse – because it causes vital immune cells to become clogged up, slowing their movement and impeding their ability to fight infection, according to new research published in the journal Cell.

Macrophages act a bit like vacuum cleaners, hoovering up debris and unwanted material within the body, including the billions of cells that die each day as part of natural turnover

Lalita Ramakrishnan

ZEISS Microscopy

Macrophage engulfing Tuberculosis bacteria

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‘Good’ cholesterol doesn’t always lower heart attack risk

cjb250 — Fri, 11 Mar 2016 09:48:43 +0000

̽��ֱ��discovery, published today in Science, could move researchers away from potentially ineffective HDL-raising drugs to treat coronary heart disease, and lead to the development of new treatments, helping to reduce their risk of heart attack.

̽��ֱ��researchers studied people with a rare genetic mutation in the SCARB1 gene, called the P376L variant, which causes the body to have high levels of ‘good’ HDL-C. High levels of ‘good’ cholesterol are commonly associated with reduced risk for coronary heart disease. Challenging this view, the researchers unexpectedly found that people with the rare mutation, who had increased levels of HDL-C, had an 80 per cent increased relative risk of the disease – a figure almost equivalent to the increased risk caused by smoking.

Coronary heart disease is responsible for nearly 70,000 deaths every year, almost entirely through heart attacks, making it the UK’s single biggest killer. ̽��ֱ��disease involves the build-up of fatty material, or plaque, in the coronary artery walls. If large quantities accumulate in the vessel walls, blood flow to the heart can become restricted or blocked, increasing risk of a heart attack.

̽��ֱ��international team of scientists included BHF-funded researchers Professor Sir Nilesh Samani at the ̽��ֱ�� of Leicester and Professor John Danesh at the ̽��ֱ�� of Cambridge. They initially looked at the DNA of 328 individuals with very high levels of HDL-C in the blood and compared them to 398 people with relatively low HDL-C. As the P376L variant they found was so rare, they then looked at its effects on HDL-C and heart disease in more than half a million additional people.

Dr Adam Butterworth, from the Cardiovascular Epidemiology Unit, ̽��ֱ�� of Cambridge, and co-investigator of this study, said: “We found that people carrying a rare genetic mutation causing higher levels of the so-called ‘good’ HDL-cholesterol are, unexpectedly, at greater risk of heart disease. This discovery could lead to new drugs that improve the processing of HDL-C to prevent devastating heart attacks.

“Large-scale collaborative research like this paves the way for further studies of rare mutations that might be significantly increasing people’s risk of a deadly heart attack. These discoveries also give researchers the knowledge we need to develop better treatments.”

Professor Peter Weissberg, Medical Director at the BHF, added said: “This is an important study that sheds light on one of the major puzzles relating to cholesterol and heart disease, which is that despite strong evidence showing HDL-C reduces heart disease risk, clinical trials on the effects of HDL-C-raising drugs have been disappointing.

“These new findings suggest that the way in which HDL-C is handled by the body is more important in determining risk of a heart attack than the levels of HDL-C in the blood. Only by understanding the underlying biology that links HDL-C with heart attacks can we develop new treatments to prevent them. These unexpected findings pave the way for further research into the SCARB1 pathway to identify new treatments to reduce heart attacks in the future.”

Additional funding for the study in the USA came from the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institute of Health.

Reference
Zanoni, P et al. Rare Variant in Scavenger Receptor BI raises HDL Cholesterol and Increases Risk of Coronary Heart Disease. Science; 10 Mar 2016; DOI: 10.1126/science.aad3517

Adapted from a press release from the British Heart Foundation

Some people with high levels of ‘good’ high density lipoprotein cholesterol (HDL-C) are at increased risk of coronary heart disease, contrary to earlier evidence that people with more HDL-C are usually at lower heart disease risk. This finding comes from an international study involving researchers at the ̽��ֱ�� of Cambridge, funded by the British Heart Foundation (BHF).

Large-scale collaborative research like this paves the way for further studies of rare mutations that might be significantly increasing people’s risk of a deadly heart attack

Adam Butterworth

geralt / Pixbay

Heart beat

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At the edge of vision: Struggling to make sense of our cluttered world

cjb250 — Wed, 25 Nov 2015 17:00:00 +0000

Even with 20/20 vision in broad daylight on a clear day, our peripheral vision can be surprisingly poor, particularly when the scene in front of us is cluttered. Now, scientists at the ̽��ֱ�� of Cambridge, UK, Northeastern ̽��ֱ��, Boston, USA, and Queensland Brain Institute, Brisbane, Australia, believe they are a step closer to understanding why this is.

“When objects in our peripheral vision are surrounded by visual clutter, a phenomenon known as ‘visual crowding’ hinders our ability to make sense of what we see,” explains Dr Will Harrison from the ̽��ֱ�� of Cambridge. “Visual crowding is ubiquitous in natural scenes and affects virtually all everyday tasks, including reading, driving and interacting with the environment. But this failure of vision isn’t a problem with our eyes – it represents a processing limit of the brain.”

Image: Focus on the green spot. Without moving your eyes, you should be able to identify the letter ‘A’ on the left side of the display; the same letter is almost impossible to see on the right side of the display.

In a study published today in the journal Current Biology, Dr Harrison and Professor Peter Bex from Northeastern ̽��ֱ�� have shed new light on how constraints in the brain limit our peripheral vision.

̽��ֱ��researchers showed volunteers a series of images with differing levels of visual crowding. To make sure they kept their eyes still, the volunteers were asked to focus on a dot. Beside the dot was a broken ring, like the letter ‘C’, but with the gap positioned at a random orientation. ̽��ֱ��volunteers were asked to estimate the angle at which the gap appeared by freely rotating a second C so that it matched the target as closely as possible. This helped the researchers to measure each individual’s uncrowded perceptual acuity.

To measure crowded perception in the next stage, the C was surrounded by an additional, larger C – a ‘distractor’ – at different orientations and/or distances to the target C. ̽��ֱ��volunteers again rotated a second C until they thought it matched the target. Whereas previous studies looking at crowding had only given binary results – was the observer right or wrong? – this new method enabled the researchers to quantify crowding as a continuous experience.

̽��ֱ��researchers found that when the angle of the target and distractor were similar, observers tended to choose an average of the two orientations. When the target and distractor angles were quite different, observers tended to choose either the correct orientation (that of the target) or they mistakenly reported the orientation of the distractor. However, this effect depended on the target and distractor being positioned very closely together – reports were not influenced by a distractor positioned a large distance away from the target.

Combining the findings with a computational model of how visual neurons represent the visual field, Dr Harrison and Professor Bex found that problems in identifying objects in our peripheral vision are due primarily to a combination of two factors. First, in a crowded scene, our visual resolution is degraded, meaning that we become less precise at locating an object’s detail. Second, we confuse which detail belongs to which object, to the extent that part of one object can appear ‘swapped’ with a part of a different object. Importantly, their model suggests that both factors are caused by the same underlying brain mechanism.

Dr Harrison believes the findings may have implications for quantifying and treating vision disorders, such as age-related macular degeneration (AMD). A large portion of the elderly population suffers from AMD, which causes debilitating central blindness. ̽��ֱ��loss of high-resolution central vision forces AMD sufferers to rely solely on peripheral vision, which is very poor due to visual crowding.

“We hope that in future it may be possible to adapt our methods to quantify the degree to which patients with AMD are visually-impaired,” explains Dr Harrison. “At the moment, it can be difficult to quantify the extent or severity of their visual deficits. Our method would allow a careful examination of the function of AMD patients’ remaining vision, which could in turn lead to better rehabilitation techniques down the track.”

̽��ֱ��research was funded by the National Institutes of Health, USA, and the National Health and Medical Research Council of Australia.

Reference
William J Harrison and Peter J Bex. A unifying model of orientation crowding in peripheral vision. Current Biology; 25 Nov 2015

As you’re driving to work along a busy road, your eyes on the traffic lights ahead, hoping they won’t turn to red, you pass signs warning of roadworks, ads on bus shelters… Suddenly a dog runs out in front of you. What are your chances of seeing it before it’s too late?

When objects in our peripheral vision are surrounded by visual clutter, a phenomenon known as ‘visual crowding’ hinders our ability to make sense of what we see

Will Harrison

Sam Saunders

Advisory Cycle Lanes and Pavements Being Abused On Parry's Lane (cropped)

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Virus evolution and human behaviour shape global patterns of flu movement

cjb250 — Mon, 08 Jun 2015 15:00:18 +0000

In the study, an international team of researchers led by the ̽��ֱ�� of Cambridge and the Fred Hutchinson Cancer Research Center, and including all five World Health Organization (WHO) Influenza Collaborating Centres, reports surprising differences between the various types of seasonal flu virus, which they show to be due to the rate at which the different viruses evolve.

There are four types of influenza viruses that cause seasonal flu in humans: two influenza A viruses (H3N2 and H1N1) and two influenza B viruses (Yamagata and Victoria). While H3N2 viruses are the most common of the seasonal influenza viruses, H1N1 and B viruses also cause epidemics worldwide each year, hence the WHO selects representative strains of all four A and B viruses for inclusion in the seasonal influenza vaccine each year.

Importantly, all four of the viruses cause indistinguishable symptoms and evolve by similar mechanisms to escape immunity induced by prior infections and vaccinations. This ‘antigenic’ evolution is part of why people get influenza multiple times over the course of their lives.

In 2008, an international team led by scientists from the ̽��ֱ�� of Cambridge, writing in the journal Science, showed that H3N2 viruses circulate continuously in east and southeast Asia throughout the year, spreading to the rest of the world each year to cause seasonal flu epidemics. Given the fundamental similarities between H3N2, H1N1, and B infection it was thought that they would also emerge from east and southeast Asia to cause yearly epidemics worldwide. However, the work published today in Nature shows that in fact, H1N1 and B viruses behave very differently from H3N2 viruses.

Senior author Dr Colin Russell, from the Department of Veterinary Medicine at the ̽��ֱ�� of Cambridge, UK, says: “While H3N2 viruses die out between epidemics and new viruses emerge from east and southeast Asia every year, H1N1 and B viruses frequently circulate continuously between epidemics worldwide. This continuous circulation gives rise to a huge diversity in H1N1 and B viruses circulating globally.”

Interestingly, the researchers found that sometimes new H1N1 and B variants emerge from outside east and southeast Asia and are subsequently seeded into Asia, while in other cases H1N1 and B variants circulate in Asia for years without spreading globally.

“It’s really surprising to find that the H3N2 viruses are unique among the seasonal influenza viruses,” adds first author Dr Trevor Bedford from the Fred Hutchinson Cancer Research Center in Seattle, USA. “It’s almost as surprising to find that the differences among viruses are associated with a simple phenomenon: how quickly the viruses evolve antigenically.”

̽��ֱ��Nature study finds that the rate of global movement of each virus, and its ability to circulate continuously between epidemics, is shaped by how quickly that virus changes its coat to escape immunity in the human population. Viruses that evolve quickly, in particular H3N2, spread around the world rapidly, but die out quickly between epidemics. Viruses that evolve more slowly, like H1N1 and B viruses, spread around the world more slowly but are also better at circulating continuously between epidemics.

̽��ֱ��key element about global movement is who is getting infected: faster evolving viruses, like H3N2, can infect adults, who tend to travel more frequently than children, providing more opportunities for the virus to spread. Conversely, more slowly evolving viruses, such as H1N1 and B viruses, primarily infect children. Children get sick with all four seasonal flu viruses, but H3N2 evolves faster so it infects adults more often. This leads to a greater proportion of adult infections with H3N2 relative to H1N1 and B viruses, and faster spread of H3N2 viruses.

“Ultimately, this means that we can look at the viruses circulating in Asia to get a good idea of which H3N2 virus might spread worldwide, but for H1N1 and B it’s tremendously variable and the dominant variant can vary from one region of the world to another,” says Dr Russell.

̽��ֱ��Nature study also sheds important light on the role of India in the global spread of seasonal influenza viruses. Scientists and public health officials had long known that China and Southeast Asia were important for the evolution and spread of seasonal influenza viruses. However, based on the analysis of an extensive collection of viruses from India, it is now clear that India may be as central as China to the ongoing evolution of seasonal influenza viruses.

“ ̽��ֱ��focus of influenza research in the past has been on China and southeast Asia, but it seems obvious now that surveillance and public health in India, home to over one sixth of the world’s population, should be a high priority for further development to help safeguard India and the world against seasonal flu,” says Dr Mandeep Chadha of the National Institute of Virology, Pune, India.

̽��ֱ��research was primarily funded by the Royal Society and US National Institutes of Health with extensive involvement of the World Health Organization’s Global Influenza Surveillance and Response System.

Reference
Bedford, T et al. Global circulation patterns of seasonal influenza viruses vary with antigenic drift. Nature; 8 June 2015.

̽��ֱ��global movement patterns of all four seasonal influenza viruses are illustrated in research published today in the journal Nature, providing a detailed account of country-to-country virus spread over the last decade and revealing unexpected differences in circulation patterns between viruses.

While H3N2 viruses die out between epidemics and new viruses emerge from east and southeast Asia every year, H1N1 and B viruses frequently circulate continuously between epidemics worldwide

Colin Russell

Matteo Bagnoli

influenza

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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