As the internet has become an integral part of modern life and its use has grown, so too has its problematic use become a growing concern across all age groups. It has provided a new environment in which a wide range of problematic behaviours may emerge, such as those relating to gaming, gambling, buying, pornography viewing, social networking, ‘cyber-bullying’ and ‘cyberchondria’, which can have mental and physical health consequences.

The newly created European Problematic Use of the Internet (EU-PUI) Research Network was formed in response to the emerging public health importance of problematic internet use and is funded through a €520,000 grant from COST (European Cooperation in Science and Technology). The network’s aims include identifying key genetic, psychological and social factors that lead people to disordered online behaviours including excessive video gaming, pornography viewing and use of social networks.

Professor Naomi Fineberg, Consultant Psychiatrist from the University of Hertfordshire and Chair of the new network, said: “Problematic Use of the Internet is a serious issue. Just about everyone uses the internet, but information on problem use is still lacking. Research has often been confined to individual countries, or problematic behaviours such as Internet gaming. So we don’t know the real scale of the problem, what causes problematic use, or whether different cultures are more prone to problematic use than others.”

The network, which includes 123 experts from 38 countries across Europe, has today published its manifesto in the journal European Neuropsychopharmacology, setting out the research priorities to help the scientific and clinical communities understand and tackle problematic internet use. These include:

• Age- and culture-appropriate assessment tools to screen, diagnose and measure the severity of different forms of problematic internet use
• Understanding its impact on health and quality of life
• Clarifying the possible role of genetics and personality features
• Consideration of the impact of social factors in its development
• Developing and testing effective interventions, both to prevent and to treat its various forms
• Identifying biomarkers, including digital markers, to improve early detection and intervention

Professor Fineberg adds: “There’s no doubt that some of the mental health problems we are looking at appear rather like addiction, such as online gambling or gaming. Some lean towards the OCD end of the spectrum, like compulsive social media checking. But we will need more than just psychiatrists and psychologists to help solve these problems. We need to bring together a range of experts, such as neuroscientists, geneticists, child and adult psychiatrists, those with lived experience of these problems and policymakers, in the decisions we make about the internet.

“We need to remember that the Internet is not a passive medium; we know that many programmes or platforms earn their money by keeping people involved and by encouraging continued participation; and they may need to be regulated – not just from a commercial viewpoint, but also from a public health perspective.”

Dr Sam Chamberlain, Consultant Psychiatrist from the University of Cambridge, who is leading research priorities for the network, added: “Despite dedicated research leading to some breakthroughs in our understanding of the psychology and biology that underpins these behaviours, we still don’t know enough about the risk factors for problematic internet use.

“The current level of evidence has to be increased to improve our ability to diagnose problems and predict an individual’s prognosis, as well as to develop effective interventions to help affected individuals and those at greatest risk.”

Reference
Fineberg, NA et al. Manifesto for a European Research Network into Problematic Usage of the Internet. European Neuropsychopharmacology; 9 Oct 2018; DOI: 10.1016/j.euroneuro.2018.08.004

The programme represents a US$30 million (£23 million) investment from Arcadia, a charitable fund of Lisbet Rausing and Peter Baldwin, in partnership with CCI, a collaboration between nine conservation organisations and the University of Cambridge seeking to transform biodiversity conservation. By catalysing strategic partnerships between leaders in research, education, policy and practice CCI aims to transform the global understanding and conservation of biodiversity and, through this, secure a sustainable future for biodiversity and society.

“We need to stop thinking about protected areas as isolated units in the landscape – we need to approach conservation at a landscape-scale if we are really going to make a difference. The Endangered Landscapes Programme is an ambitious attempt to apply ‘more, bigger, better and joined’, at a landscape-scale, right across Europe,” said Professor Sir John Lawton, Chair of the ELP Oversight and Selection Panel.

The ELP aims to deliver an ambitious vision for the future in which landscapes:

• Support viable populations of native species with the capacity for landscape-scale movement;
• Provide space for the natural functioning of ecological processes, so reducing or even eliminating the need for intensive management;
• Are resilient to short and longer-term change (such as climate fluctuations);
• Provide sustainable cultural, social and economic benefits to people.

Included in the initial group of ELP-funded projects are plans to return predatory sandbar sharks and Mediterranean monk seals to the seas off the coast of Turkey; create opportunities for key species such as wolves, moose, European bison and greater spotted eagles to move more freely in the vast Prypiat Polesia area of Belarus and Ukraine; establish one of Europe’s largest wilderness areas in the Carpathian Mountains of Romania; and restore Caledonian pinewoods to some of the UK’s most spectacular landscapes in the Scottish Highlands.

“Lisbet Rausing and Peter Baldwin have united Cambridge in common cause with our closest neighbours, reflecting our best selves, our best interests, and the best hope for future generations,” said Professor Stephen J Toope, Vice-Chancellor of the University of Cambridge.

Alongside this ecological work, the projects include conservation enterprise programmes, based on nature-based businesses that will provide income, employment and cultural benefits for communities and landowners. CCI will support the project recipients and help drive the success of the ELP as a model for landscape-scale restoration throughout Europe by:

• Supporting participatory planning and development of new and innovative landscape restoration initiatives;
• Building capacity nationally and locally, by facilitating the transfer of skills and know-how between individuals and institutions;
• Sharing knowledge, lessons and experience to help deliver strategies, policies and technical information required for creating sustainable landscapes;
• Demonstrating to decision-makers the environmental, social and economic benefits that are possible from the recovery of nature and ecosystem processes.

The accelerating loss of the natural world represents one of the greatest challenges of the 21st century. Building a better future requires a better understanding of nature and its values to people, and the practical interventions required to support economic, social and political transitions towards more equitable and effective stewardship of the planet. It is the ambition of Arcadia and CCI that the ELP will not only be effective in achieving its own aims but that it will inspire others across Europe and the world to consider how they, too, can work to restore and improve landscapes for the future.

“Landscape-scale restoration ecology works. Nature is out there: waiting. Let’s invite her back in. Together we will restore and rewild, and thus protect, Europe – our home, our continent, our love,” said Dr Lisbet Rausing, Founder, Arcadia Fund.

Using information from ten different cities around the world, the researchers, led by the University of Cambridge, have developed a model that can predict with 80% accuracy whether a new business will fail within six months. The results will be presented at the ACM Conference on Pervasive and Ubiquitous Computing (Ubicomp), taking place this week in Singapore.

While the retail sector has always been risky, the past several years have seen a transformation of high streets as more and more retailers fail. The model built by the researchers could be useful for both entrepreneurs and urban planners when determining where to locate their business or which areas to invest in.

“One of the most important questions for any new business is the amount of demand it will receive. This directly relates to how likely that business is to succeed,” said lead author Krittika D’Silva, a Gates Scholar and PhD student at Cambridge’s Department of Computer Science and Technology. “What sort of metrics can we use to make those predictions?”

D’Silva and her colleagues used more than 74 million check-ins from the location technology platform Foursquare from Chicago, Helsinki, Jakarta, London, Los Angeles, New York, Paris, San Francisco, Singapore and Tokyo; and data from 181 million taxi trips from New York and Singapore.

Using this data, the researchers classified venues according to the properties of the neighbourhoods in which they were located, the visit patterns at different times of day, and whether a neighbourhood attracted visitors from other neighbourhoods.

“We wanted to better understand the predictive power that metrics about a place at a certain point in time have,” said D’Silva.

Whether a business succeeds or fails is normally based on a number of controllable and uncontrollable factors. Controllable factors might include the quality or price of the store’s product, its opening hours and its customer satisfaction. Uncontrollable factors might include unemployment rates of a city, overall economic conditions and urban policies.

“We found that even without information about any of these uncontrollable factors, we could still use venue-specific, location-related and mobility-based features in predicting the likely demise of a business,” said D’Silva.

The data showed that across all ten cities, venues that are popular around the clock, rather than just at certain points of day, are more likely to succeed. Additionally, venues that are in demand outside of the typical popular hours of other venues in the neighbourhood tend to survive longer. The data also suggested that venues in diverse neighbourhoods, with multiple types of businesses, tend to survive longer.

While the ten cities had certain similarities, the researchers also had to account for their differences.

“The metrics that were useful predictors vary from city to city, which suggests that factors affect cities in different ways,” said D’Silva. “As one example, that the speed of travel to a venue is a significant metric only in New York and Tokyo. This could relate to the speed of transit in those cities or perhaps to the rates of traffic.”

To test the predictive power of their model, the researchers first had to determine whether a particular venue had closed within the time window of their data set. They then ‘trained’ the model on a subset of venues, telling the model what the features of those venues were in the first time window and whether the venue was open or closed in a second time window. They then tested the trained model on another subset of the data to see how accurate it was.

According to the researchers, their model shows that when deciding when and where to open a business, it is important to look beyond the static features of a given neighbourhood and to consider the ways that people move to and through that neighbourhood at different times of day. They now want to consider how these features vary across different neighbourhoods in order to improve the accuracy of their model.

Reference:
Krittika D’Silva et al. ‘The Role of Urban Mobility in Retail Business Survival.’ Paper presented to the Ubicomp 2018, Singapore, 8-12 October 2018.  http://ubicomp.org/ubicomp2018/program/program.html#s36

The definitive architecture of the mammalian body is established shortly after the embryo implants into the uterus. This body plan has spatial references, or axes, that guide the emergence of tissues and organs: an antero-posterior axis defined by the head at one end and the tail at the other, an orthogonal dorso-ventral axis and a medio-lateral axis, which orientates the arrangement of internal organs like the liver, pancreas or the heart.

Studying the processes orchestrating the formation of early mammalian embryos is hampered by the difficulty in obtaining them. Earlier findings from the Cambridge group had shown that embryonic stem cells could self-organise in culture into structures with an antero-posterior polarity.

Now, in collaboration with researchers from the University of Geneva and the Swiss Federal Institute of Technology Lausanne (EPFL), they have extended the cultures to reveal a capacity of mouse stem cells to produce ‘pseudo-embryos’ that display some of the important characteristics of a normal mouse embryo. Established from only 300 embryonic stem cells, these structures, called ‘gastruloids’, exhibit developmental features and organisation comparable to the posterior part of a six to ten day-old embryo.

The study shows that gastruloids organise themselves with regard to the three main body axes, as they do in embryos, and follow similar patterns of gene expression. One example of this is the pattern of expression of Hox genes, an ensemble of genes that are expressed in a precise sequential order in the embryo and act as landmarks for different aspects of the body, including the position of different vertebrae or of limbs. This degree of organisation makes gastruloids a remarkable system for the study of the early stages of normal or abnormal embryonic development in mammals.

“These results significantly extend our earlier findings. We were surprised to see how far gastruloids develop, their complex organisation and the presence of early-stage tissues and organ,” says Professor Alfonso Martinez Arias, leader of the University of Cambridge team, at its Department of Genetics.

Professor Denis Duboule from the University of Geneva and at the EPFL explained, “To determine whether gastruloids organise themselves into bona fide embryonic structures, we characterised their level of genetic activity at different stages of development”.

The researchers identified and quantified the RNA transcribed from gastruloids and compared the expressed genes with those of mouse embryos at comparable stages of development, which showed there was a high degree of similarity.

“Gastruloids form structures similar to the posterior part of the embryo, from the base of the brain to the tail, whose development program is somewhat different from that of the head,” says Dr Leonardo Beccari, co-first author of the study, from the University of Geneva.

These embryo-like structures express genes characteristic of the various types of progenitor cells necessary for the constitution of future tissues.

“The complexity of gene expression profiles increases over time, with the appearance of markers from different embryonic cell lineages, much like the profiles observed in control embryos,” adds Dr Naomi Moris from the Cambridge team, co-first author of the article.

“The implementation of the Hox gene network over time, which mimics that of the embryo, particularly confirms the remarkably high level of self-organisation of gastruloids,” explains Mehmet Girgin, co-first author of the study and PhD student at the Institute of Bioengineering at EPFL.

The researchers say that these pseudo-embryos will allow an alternative method to animal research, in accordance with the principle of the ‘3Rs’ (the reduction, replacement and refinement of the use of animals in research). The finding that so much of the development of an embryo can be recapitulated using stem cells will also increase researchers’ ability to study the genetic mechanisms underlying normal development and disease.

Earlier in the year, the group led by Professor Magdalena Zernicka-Goetz at the Department of Physiology, Development and Neuroscience at the University of Cambridge reported embryo-like structures capable of generating an anteroposterior axis but which required additional, extra-embryonic, stem cells to generate anteroposterior polarity. The new work shows surprisingly that stem cells can self-organise the three axes independently of the extra-embryonic tissues.

“It makes things much simpler for research,” says Professor Martinez Arias. “Not only do gastruloids self-organise to generate the three axes, but they also mimic the spatial and temporal patterns of embryos, without extra-embryonic tissue. This suggests that gastruloids can become a useful tool, particularly in understanding gene expression during development.”

This work was largely funded by the Biotechnology and Biological Sciences Research Council (BBSRC), the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), the Engineering and Physical Sciences Research Council (EPSRC) and the European Research Council.

Adapted from a press release from the University of Geneva.

Reference
Beccari, L, Moris, N, Girgin, M, et al. Multi-axial self-organisation properties of mouse embryonic stem cells into gastruloids. Nature; 3 Oct 2018; DOI: 10.1038/s41586-018-0578-0

Image caption
Seven-day old gastruloid. The cell nuclei are marked in blue. Neural progenitor cells (green) are distributed along the antero-posterior axis. Progenitor cells of the tail bud (pink) are confined to the posterior extremity of the gastruloid and indicate the direction of its elongation. © Mehmet Girgin, EPFL

The first pharmaceutical based on this method, adalimumab, was approved in 2002 and is used for rheumatoid arthritis, psoriasis and inflammatory bowel diseases. Since then, phage display has produced antibodies that can neutralise toxins, counteract autoimmune diseases and cure metastatic cancer.

The Royal Swedish Academy of Sciences announced the 2018 Prize this morning with one half to Frances H. Arnold and the other half jointly to George P. Smith and Sir Gregory P. Winter.

The Nobel Assembly said: “The 2018 Nobel Laureates in Chemistry have taken control of evolution and used it for purposes that bring the greatest benefit to humankind. Enzymes produced through directed evolution are used to manufacture everything from biofuels to pharmaceuticals. Antibodies evolved using a method called phage display can combat autoimmune diseases and in some cases cure metastatic cancer.”

Winter, the Master of Trinity College, is a genetic engineer and is best known for his research and inventions relating to humanised and human therapeutic antibodies. Sir Gregory is a graduate of Trinity College and was a Senior Research Fellow before becoming Master.

His research career has been based almost entirely in Cambridge at the Medical Research Council’s Laboratory of Molecular Biology and the Centre for Protein Engineering, and during this time he also founded three Cambridge biotech companies based on his inventions: Cambridge Antibody Technology (acquired by AstraZeneca), Domantis (acquired by GlaxoSmithKline) and Bicycle Therapeutics.

Winter becomes the 107th Affiliate of Cambridge to be awarded a Nobel Prize. Born in 1951 in Leicester, Sir Greg studied Natural Sciences at Trinity College, Cambridge, and was awarded his PhD, also from Cambridge, in 1977.

“It came as a bit of a shock, and I felt a bit numb for a while. It’s almost like you’re in a different universe,” said Winter, on hearing he had been jointly awarded the Prize.

“For a scientist, a Nobel Prize is the highest accolade you can get, and I’m so lucky because there are so many brilliant scientists and not enough Nobel Prizes to go around.”

The University’s Vice-Chancellor, Professor Stephen Toope, said: “I am thrilled to hear that Sir Greg Winter has been awarded this year’s Nobel Prize in Chemistry. Greg’s work has been vital in the development of new therapies for debilitating health conditions such as rheumatoid arthritis, and has led to breakthroughs in cancer care. These advances continue to transform the lives of people across the world.

“It gives me the greatest pleasure, on behalf of our community, to congratulate the University of Cambridge’s latest Nobel Prize winner.”

Patrick Maxwell, Regius Professor of Physic and Head of the School of Clinical Medicine at the University of Cambridge, said: “I am absolutely delighted that Sir Greg’s work has been recognised with a Nobel Prize. The work for which the prize is awarded was carried out on the Cambridge Biomedical Campus. It directly led to the power of monoclonal antibodies being harnessed for treatment of disease. His inventions really have produced silver bullets that have transformed the way medicine is practised.”

Professor Sir Alan Fersht, former Master of Gonville and Caius, collaborated with Winter on early protein engineering work. “Greg Winter is an outstandingly creative scientist of a practical bent,” he said.

“He has applied his skills and imagination to the benefit of humankind to create, amongst other inventions, novel engineered antibodies that have formed the basis of a new pharmaceutical industry to treat disease and cancer. It is a thoroughly worthy Nobel Prize.”

Professor Dame Carol Robinson, Royal Society of Chemistry president, said: “Today’s Nobel Prize in chemistry highlights the tremendous role of chemistry in contributing to many areas of our lives including pharmaceuticals, detergents, green catalysis and biofuels. It is a great advert for chemistry to have impact in so many areas.

“Directed evolution of enzymes and antibody technology are subjects that I have followed with keen interest; both are now transforming medicine. It would have been hard to predict the outcome of this research at the start – this speaks to the need for basic research.

“I am delighted to see these areas of chemistry recognised and congratulate all three Nobel Laureates.”

Frances H. Arnold, who also shared today’s Prize, conducted the first directed evolution of enzymes, which are proteins that catalyse chemical reactions. Since then, she has refined the methods that are now routinely used to develop new catalysts. The uses of Frances Arnold’s enzymes include more environmentally friendly manufacturing of chemical substances, such as pharmaceuticals, and the production of renewable fuels for a greener transport sector.

In 1985, George Smith developed an elegant method known as phage display, where a bacteriophage – a virus that infects bacteria – can be used to evolve new proteins.

More details on previous Cambridge winners can be found here: https://www.cam.ac.uk/research/research-at-cambridge/nobel-prize

You can read more about the 2018 Nobel Prize in Chemistry here: https://www.nobelprize.org/uploads/2018/10/popular-chemistryprize2018.pdf

View image on Twitter

The Nobel Prize

✔@NobelPrize

Sir Gregory Winter, awarded the #NobelPrize in Chemistry, has used phage display to produce new pharmaceuticals. Today phage display has produced antibodies that can neutralise toxins, counteract autoimmune diseases and cure metastatic cancer.

10:49 AM – Oct 3, 2018

• 1,207

• 1,034 people are talking about this

Twitter Ads info and privacy

Self-reported behaviour and perceptions

Question-asking behaviour

Recommendations

• Where possible, seminar organisers should avoid placing limits on the time available for questions. Alternatively, moderators should endeavour to keep each question and answer short to allow more questions to be asked.
• Moderators should prioritise a female-first question, be trained to ‘see the whole room’ and maintain as much balance as possible with respect to gender and seniority of question-askers.
• Seminar organisers are encouraged not to neglect inviting internal speakers.
• Organisers should consider providing a small break between the talk and the question period to give attendees more time to formulate a question and try it out on a colleague.

Researchers from the University of Cambridge will shortly begin clinical trials of a new vaccine that builds on almost two decades of research to protect against diseases caused by RNA viruses. At the same time, they will begin studying the natural animal reservoirs of the viruses in an attempt to try and predict which strains are likely to cause future outbreaks, information that will be essential for creating effective vaccines.

Ebola, Lassa and Marburg viruses cause haemorrhagic fever, leading to severe disease, often with high mortality rates. Outbreaks can cause devastating local epidemics in the human population and to wildlife, including non-human primates. The recent Ebola epidemic in West Africa (2013–2016) killed over 11,000 people and devastated the infrastructure and economies of Liberia, Sierra Leone and Guinea.

A new approach to vaccine development

Professor Jonathan Heeney and colleagues at the Lab of Viral Zoonotics, University of Cambridge, have developed and successfully tested a trivalent vaccine in guinea pigs that protects against Ebola, Lassa and Marburg viruses. As a result, Professor Heeney has been awarded a further £2 million by Innovate UK and the Department of Health and Social Care to take the vaccine to clinical trials in humans.

The research takes a new approach pioneered by Professor Heeney and builds on Cambridge’s strengths in genomics, monoclonal antibody research and computational biology. It has led to the formation of DIOSynVax, a spin-out company of Cambridge Enterprise.

A virus’s genetic code is written into its RNA (just as ours is written into our DNA), which leads to the generation of proteins. When we are infected by a virus, our immune system responds to these proteins, known as ‘antigens’, producing antibodies that can identify and try to eliminate the invading pathogen.

The approach developed by Professor Heeney involves understanding how the immune system correctly identifies the virus from its proteins, and using this information to create ‘viruses’ that can generate an immune response. Using monoclonal antibodies – copies of antibodies taken from survivors of the target diseases – they can then test whether the body can effectively eliminate these fake viruses, leading to protection.

“We’ve taken fundamental science that stretches back almost two decades and developed a new approach to vaccine development,” says Professor Heeney. “This has the potential to dramatically reduce the time needed to produce new vaccines and change the way in which the industry makes them.”

With the new funding, the team hopes to scale up production while ensuring that the quality of the vaccine is maintained. They will then carry out toxicity tests in animals and human blood samples to test for potential adverse effects; if successful, they will then trial the vaccine in healthy human volunteers.

The funding is part of a £5m commitment from the Department of Health and Social Care to fund five projects to develop new vaccines with a ‘One Health’ focus, considering how the environment, the health of animals and the health of humans interact. This sits within the government’s £120m UK aid commitment to develop vaccines to help tackle diseases with epidemic potential.

Predicting the next outbreak

In recent Ebola outbreaks, the approach used successfully by the World Health Organization is known as ‘ring vaccination’, focused on vaccinating and monitoring a ring of people around each infected individual. However, this approach can only be used in response to an outbreak. In order for a vaccine to be used proactively – to prevent an outbreak in the first place – it is necessary to predict which strain or strains of a virus are most likely to cause future epidemics.

“A disproportionally high number of emerging and re-emerging diseases – from Ebola and Lassa through to rabies and influenza – are caused by RNA viruses carried naturally by animals,” says Professor Heeney. “We know very little about the viral diversity within these reservoir species and what enables them to spread to humans – and hence where the likely future threats lie.”

Viral genomes are notoriously variable due to the high mutation rates that occur during replication. These accumulate over time and result in evolution of the viruses as they circulate in their natural animal reservoir populations. If some viral variants arise and are able to adapt to use human cell receptors and are then able to escape immune defences, they may become highly infectious and cause large disease outbreaks.

“Vaccines are only as good as the antigen immune targets of the virus that they are designed for,” adds Professor Heeney. “If the antigen changes, the vaccine will no longer be effective. In most cases, current vaccine candidates against RNA viruses are from past human outbreaks with little or no information of future risks from viral variants carried in animal reservoirs, especially those with the potential for animal-to-human transmission.”

Professor Heeney has also received £1.4 million from the Biotechnology and Biological Sciences Research Council (BBSRC) to lead a project that aims to predict where future outbreaks may arise from and the likely strains, and to then use this knowledge to inform vaccine design. This One Health project enlists veterinarians, clinicians, ecologists and medical and public health workers in West Africa to understand how people catch Lassa fever from rat populations. Their work will include trapping rat species that carry these viruses and placing GPS tags to monitor their movements, as well as obtaining molecular, genomic and antibody data from the animals and viral sequences from infected rats.

Professor Melanie Welham, Executive Chair of BBSRC, says: “This important research from the team at the University of Cambridge is about providing effective treatments for some potentially deadly diseases spread by rats and bats: Lassa and Ebola respectively. Novel strategies to combat dangerous infections like these are essential and often underpin the development of much-needed next generation vaccines.

“Professor Heeney and team have already made a significant difference in this area, researching cross species transmissions of these viruses, with a view to developing vaccines for Ebola and Lassa that would be effective against multiple strains.”

In addition, the team is collaborating with Professor James Wood, Head of the Department of Veterinary Medicine at Cambridge, who is conducting a complementary study funded by the Global Challenges Research Fund to sample bat colonies in Ghana, believed to be a natural reservoir for the Ebola virus.

“Equipped with this information, we should be able to design better vaccine antigens for more effective and broadly-protective vaccines,” says Professor Heeney. “Combined with our accelerated vaccine development platform, this has the potential to have an enormous positive impact on global public health.”

Academics at the University of Cambridge and at Lund University in Sweden have devised the first strategy to ‘go after’ the cause of the devastating disease, which could eventually lead to the development of new drugs to treat dementia. Their findings are reported in the journal PNAS.

“This is the first time that a systematic method to go after the pathogens – the cause of Alzheimer’s disease – has been proposed,” said Professor Michele Vendruscolo from Cambridge’s Department of Chemistry, the paper’s senior author. “Until very recently scientists couldn’t agree on what the cause was so we didn’t have a target. As the pathogens have now been identified as small clumps of proteins known as oligomers, we have been able to develop a strategy to aim drugs at these toxic particles.”

Alzheimer’s disease leads to the death of nerve cells and tissue loss throughout the brain. Over time, the brain shrinks dramatically and the cell destruction causes memory failure, personality changes, and problems carrying out daily activities.

Scientists identified abnormal deposits called protein oligomers as the most likely suspects of the cause of dementia. Although proteins are normally responsible for important cell processes, when people have Alzheimer’s disease these proteins become rogue, form clumps and kill healthy nerve cells.

“A healthy brain has a quality control system that effectively disposes of potentially dangerous masses of proteins, known as aggregates,” said Vendruscolo. “As we age, the brain becomes less able to get rid of the dangerous deposits, leading to disease. It is like a household recycling system, if you have an efficient system in place then the clutter gets disposed of in a timely manner. If not, over time, you slowly but steadily accumulate junk that you don’t need. It is the same in the brain.”

The research was carried out by an international team of scientists that also included Professor Sir Christopher Dobson, Master of St John’s College, University of Cambridge, at the Centre for Misfolding Diseases (CMD), which he co-founded. “This interdisciplinary study shows that it is possible not just to find compounds that target the toxic oligomers that give rise to neurodegenerative disorders but also to increase their potency in a rational manner,” he said. “It now makes it possible to design molecules that have specific effects on the various stages of disorders such as Alzheimer’s disease, and hopefully to convert them into drugs that can be used in a clinical environment.”

There have been approximately 400 clinical trials for Alzheimer’s disease but none of them has specifically targeted the pathogens that cause it. In the UK, dementia is the only condition in the top 10 causes of death without a treatment to prevent, cure or slow its progression.

“Our research is based on the major conceptual step of identifying protein oligomers as the pathogens and reports a method to systematically develop compounds to target them. This approach enables a new drug discovery strategy,” said Vendruscolo.

The team believes their first drug candidates could reach clinical trials in around two years. They have co-founded Wren Therapeutics, a biotechnology company based in the newly opened Chemistry of Health building, whose mission is to take the ideas developed at Cambridge and translate them into finding new ways to diagnose and treat Alzheimer’s disease and other misfolding disorders.

The group’s new strategy is based on a chemical kinetics approach developed in the last ten years by scientists led jointly by Professor Tuomas Knowles, also a Fellow at St John’s College, Professor Dobson and Professor Vendruscolo, working at the new centre in Cambridge, in collaboration with scientists at Lund University led by Professor Sara Linse.

“Since the process of aggregation is highly dynamic, the framework of kinetics allows us to approach this problem in a new way and find approaches to stop the generation of toxic proteins species at their very source,” said Knowles.

“This is a detailed academic study looking at how quickly compounds are able to stop amyloid building up into toxic clumps, which are characteristic of Alzheimer’s disease,” said Dr David Reynolds, Chief Scientific Officer from Alzheimer’s Research UK. “With no treatments to slow or stop the diseases that cause dementia, it’s vital we improve approaches like this that could help refine the drug discovery progress and accelerate new treatments for people living with Alzheimer’s.”

Reference:
Sean Chia et al. ‘SAR by kinetics for drug discovery in protein misfolding diseases.’ PNAS (2018). DOI: 10.1073/pnas.1807884115

Adapted from a St John’s College press release.

The researchers, led by the University of Cambridge, applied an experimental gene therapy treatment in mice and were able to successfully target and eliminate the damaged DNA in mitochondria which causes the devastating conditions.

Their results, published in the journal Nature Medicine, could provide a practical route to treating patients with these diseases and may provide a future alternative to mitochondrial replacement therapy, or ‘three-parent IVF’. This is the first time programmable genome engineering tools have been used inside a living animal, resulting in such significant modification of mitochondrial DNA.

Mitochondria are the powerhouses inside our cells, producing energy and carrying their own DNA. They are inherited from a person’s mother via the egg, but if they are damaged, it can result in a serious mitochondrial disease. For example, MELAS Syndrome is a severe multi-system disorder causing progressive loss of mental and movement abilities, which usually becomes apparent in early childhood.

There are typically about 1000 copies of mitochondrial DNA per cell, and the percentage of these that are damaged, or mutated, will determine whether a person will suffer from mitochondrial disease or not. Usually, more than 60% of the mitochondrial DNA molecules in a cell need to be mutated for the disease to emerge, and the more mutated mitochondrial DNA a person has, the more severe their disease will be. Conversely, if the percentage of mutated DNA can be reduced, the disease could potentially be treated.

Mitochondrial diseases are currently incurable, although a new IVF technique of mitochondrial transfer gives families affected by mitochondrial disease the chance of having healthy children – removing affected mitochondria from an egg or embryo and replacing them with healthy ones from a donor.

“Mitochondrial replacement therapy is a promising approach to prevent transmission of mitochondrial diseases, however, as the vast majority of mitochondrial diseases have no family history, this approach might not actually reduce the proportion of mitochondrial disease in the population,” said Dr Payam Gammage, a postdoctoral researcher in the MRC Mitochondrial Biology Unit, and the paper’s first author.

“One idea for treating these devastating diseases is to reduce the amount of mutated mitochondrial DNA by selectively destroying the mutated DNA, and allowing healthy DNA to take its place,” said Dr Michal Minczuk, also from the Medical Research Council (MRC) Mitochondrial Biology Unit, and the study’s senior author.

To test an experimental gene therapy treatment, which has so far only been tested in human cells grown in petri dishes in a lab, the researchers used a mouse model of mitochondrial disease that has the same mutation as some human patients.

The gene therapy treatment, known as the mitochondrially targeted zinc finger-nuclease, or mtZFN, recognises and then eliminates the mutant mitochondrial DNA, based on the DNA sequence differences between healthy and mutant mitochondrial DNA. As cells generally maintain a stable number of mitochondrial DNA copies, the mutated copies that are eliminated are replaced with healthy copies, leading to a decrease in the mitochondrial mutation burden that results in improved mitochondrial function.

The treatment was delivered into the bloodstream of the mouse using a modified virus, which is then mostly taken up by heart cells. The researchers found that the treatment specifically eliminates the mutated mitochondrial DNA, and resulted in measures of heart metabolism improving.

Following on from these results, the researchers hope to take this gene therapy approach through clinical trials, in the hope of producing an effective treatment for mitochondrial diseases.

This work was supported by the Medical Research Council and was performed in collaboration with Sangamo Therapeutics and the Max Planck Institute for Biology of Ageing in Cologne.

Reference: 
Payam A. Gammage et al. ‘Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo.’ Nature Medicine (2018). DOI: 10.1038/s41591-018-0165-9.

The Rising Path is part of the Garden’s Understanding Plant Diversity Project, a three year project supported by The Monument Trust, which aims to revitalise the contemporary relevance of the Garden’s Systematic Beds for researchers, teachers and visitors by exploring how plant diversity is identified and organised – the science of plant taxonomy.

Professor Beverley Glover, Director of the Botanic Garden, said: “We are thrilled to be opening the Rising Path to the public. This innovative structure is a key part of an ongoing project to re-examine, re-interpret and re-display our Systematic Beds which will help visitors, students and scientists to understand more about plants, how they are related, and why this is so important for science.”

Rising Path Project Manger, Juliet Day, said: “Observation is the cornerstone of all scientific enquiry and plants are full of shapes, patterns, numbers, colours, textures, symmetry, scents and tastes to discover. We have developed the Rising Path and created interpretation displays to encourage visitors of all ages to explore the Systematic Beds and enjoy looking more closely at plants.”

The Rising Path leads to a viewing platform where visitors will be able to see the full extent and layout of the Systematic Beds from a 3m high vantage point. Rest points along the path highlight the innovations that allowed plants to leave the water for life on land and to proliferate into the 400,000 species known today.

At ground level, an interpretation hub expands on the twin educational purpose of the Systematic Beds: how to look at plants, and how to organise those plants in order to provide a robust framework for effective research and communication.

Added Glover “For thousands of years, humans have grouped plants into families based on observation made using the naked eye. Today, scientists also study the DNA of plants to determine relationships. Changes in scientific understanding pose interesting challenges for a Garden that seeks to be both guardian of a historic landscape and relevant to contemporary research.”

The Systematic Beds occupy nearly three acres of CUBG and are of global heritage significance. They were designed in 1845 by CUBG’s first Curator, Andrew Murray, and their design uniquely translates the leading botanic text book of the time by Augustin de Candolle into a display on the ground to represent and teach plant taxonomy – the science of identifying and classifying plant species.

The Understanding Plant Diversity project, which includes the Rising Path, seeks to ensure the Systematic Beds remain a useful teaching tool in the modern world. When renovation is complete in 2019, the Systematic Beds will represent 1,600 plant species belonging to about 78 families dispersed across 119 beds.

Agriculture that appears to be more eco-friendly but uses more land may actually have greater environmental costs per unit of food than “high-yield” farming that uses less land, a new study has found.

There is mounting evidence that the best way to meet rising food demand while conserving biodiversity is to wring as much food as sustainably possible from the land we do farm, so that more natural habitats can be “spared the plough”.

However, this involves intensive farming techniques thought to create disproportionate levels of pollution, water scarcity and soil erosion. Now, a study published today in the journal Nature Sustainability shows this is not necessarily the case.

Scientists have put together measures for some of the major “externalities” – such as greenhouse gas emission, fertiliser and water use – generated by high- and low-yield farming systems, and compared the environmental costs of producing a given amount of food in different ways.

Previous research compared these costs by land area. As high-yield farming needs less land to produce the same quantity of food, the study’s authors say this approach overestimates its environmental impact.

Their results from four major agricultural sectors suggest that, contrary to many people’s perceptions, more intensive agriculture that uses less land may also produce fewer pollutants, cause less soil loss and consume less water.

However, the team behind the study, led by scientists from the University of Cambridge, caution that if higher yields are simply used to increase profit or lower prices, they will only accelerate the extinction crisis we are already seeing.

“Agriculture is the most significant cause of biodiversity loss on the planet,” said study lead author Andrew Balmford, Professor of Conservation Science from Cambridge’s Department of Zoology. “Habitats are continuing to be cleared to make way for farmland, leaving ever less space for wildlife.”

“Our results suggest that high-yield farming could be harnessed to meet the growing demand for food without destroying more of the natural world. However, if we are to avert mass extinction it is vital that land-efficient agriculture is linked to more wilderness being spared the plough.”

The Cambridge scientists conducted the study with a research team from 17 organisations across the UK and around the globe, including colleagues from Poland, Brazil, Australia, Mexico and Colombia.

The study analysed information from hundreds of investigations into four vast food sectors, accounting for large percentages of the global output for each product: Asian paddy rice (90%), European wheat (33%), Latin American beef (23%), and European dairy (53%).

Examples of high-yield strategies include enhanced pasture systems and livestock breeds in beef production, use of chemical fertilizer on crops, and keeping dairy cows indoors for longer.

The scientists found data to be limited, and say more research is urgently needed on the environmental cost of different farming systems. Nevertheless, results suggest many high-yield systems are less ecologically damaging and, crucially, use much less land.

For example, in field trials, inorganic nitrogen boosted yields with little to no greenhouse gas “penalty” and lower water use per tonne of rice. Per tonne of beef, the team found greenhouse gas emissions could be halved in some systems where yields are boosted by adding trees to provide shade and forage for cattle.

The study only looked at organic farming in the European dairy sector, but found that – for the same amount of milk – organic systems caused at least one third more soil loss, and take up twice as much land, as conventional dairy farming.

Co-author Professor Phil Garnsworthy from the University of Nottingham, who led the dairy team, said: “Across all dairy systems we find that higher milk yield per unit of land generally leads to greater biological and economic efficiency of production. Dairy farmers should welcome the news that more efficient systems have lower environmental impact.”

Conservation expert and co-author Dr David Edwards, from the University of Sheffield, said: “Organic systems are often considered to be far more environmentally friendly than conventional farming, but our work suggested the opposite. By using more land to produce the same yield, organic may ultimately accrue larger environmental costs.”

The study authors say that high-yield farming must be combined with mechanisms that limit agricultural expansion if they are to have any environmental benefit. These could include strict land-use zoning and restructured rural subsidies.

“These results add to the evidence that sparing natural habitats by using high-yield farming to produce food is the least bad way forward,” added Balmford.

“Where agriculture is heavily subsidised, public payments could be contingent on higher food yields from land already being farmed, while other land is taken out of production and restored as natural habitat, for wildlife and carbon or floodwater storage.”

The mentoring of junior colleagues can reduce anxiety and improve the mental health of the mentors themselves in high-pressure occupations, concludes a new study co-authored at Cambridge Judge Business School involving an English police force.

While previous research had indicated that the anxiety of mentees can be reduced through the guidance of more senior mentors, the new study finds that imparting knowledge and experience can also help mentors by making their jobs more rewarding.

“We found that mentoring relationships provide a unique context for mentors to discuss and normalise their concerns, to share ideas for managing anxieties, and to find more meaning in their work,” concludes the study, published in the Journal of Vocational Behavior.

“Mentoring relationships appeared to provide an organisational mechanism to prompt supervisor and colleague interactions, which in turn facilitated a reduction in the mentors’ anxiety.”

In England alone, mental illness accounts for annual expenditure on healthcare of £14 billion and a reduction in gross domestic product of £52 billion owing to people unable to work to their full capacity.

Policing was chosen as an appropriate setting to study how mentoring can reduce anxiety in occupations that play important social roles, including the medical profession and the military – roles that require mental strength in challenging situations coupled with political pressure to become more efficient. The study follows a mentoring programme that was rolled out at one of 43 territory-based police forces in England and Wales since 2013.

Despite the pressures of their roles – including threats, abuse, snap decisions and the risk of death – police officers tend not to seek support from other officers, including more senior colleagues, to avoid “negative stigma” associated with mental health disorders. Mentoring can help fill this void, the study says.

“The study suggests that a relatively inexpensive practice such as mentoring can help reduce anxiety among both senior and junior staff, and this could help organisations address the serious and costly workplace issues of anxiety and mental health,” says study co-author Dr Thomas Roulet, University Senior Lecturer in Organisation Theory at Cambridge Judge Business School. “While the study focused on high-stress roles in the public eye, we believe that the findings may also apply to other occupations that also have anxiety-provoking pressures.”

The study is co-authored by Dr Michael Gill of Said Business School at Oxford University and Chief Inspector Stephen Kerridge of the Cambridgeshire Constabulary.

Excerpts of interviews with mentors and mentees indicated that it was beneficial for people in such busy and often frantic jobs as policing to have an opportunity to be “listened to” and to take note of the fact that “we’ve all gone through” certain work experiences.

“Mentoring provided reassurance to the mentors by illuminating how other, often junior officers also experience anxiety thereby normalising their own experiences,” the study says. “By acknowledging that anxieties are common, both the mentees and mentors in this study appeared to be more comfortable discussing such issues and therefore in developing different coping mechanisms.”

Reference: 
Michael J. Gill et al. ‘Mentoring for mental health: A mixed-method study of the benefits of formal mentoring programmes in the English police force.’ Journal Of Vocational Behavior (2018). DOI: 10.1016/j.jvb.2018.08.005

Originally published on the Cambridge Judge Business School website. 

Photosynthesis is the process plants use to convert sunlight into energy. Oxygen is produced as a by-product of photosynthesis when the water absorbed by plants is ‘split’. It is one of the most important reactions on the planet because it is the source of nearly all of the world’s oxygen. Hydrogen which is produced when the water is split could potentially be a green and unlimited source of renewable energy.

A new study, led by academics at the University of Cambridge, used semi-artificial photosynthesis to explore new ways to produce and store solar energy. They used natural sunlight to convert water into hydrogen and oxygen using a mixture of biological components and manmade technologies.

The research could now be used to revolutionise the systems used for renewable energy production. A new paper, published in Nature Energy, outlines how academics at the Reisner Laboratory in Cambridge’s Department of Chemistry developed their platform to achieve unassisted solar-driven water-splitting.

Their method also managed to absorb more solar light than natural photosynthesis.

Katarzyna Sokół, first author and PhD student at St John’s College, said: “Natural photosynthesis is not efficient because it has evolved merely to survive so it makes the bare minimum amount of energy needed – around 1-2 per cent of what it could potentially convert and store.”

Artificial photosynthesis has been around for decades but it has not yet been successfully used to create renewable energy because it relies on the use of catalysts, which are often expensive and toxic. This means it can’t yet be used to scale up findings to an industrial level.

The Cambridge research is part of the emerging field of semi-artificial photosynthesis which aims to overcome the limitations of fully artificial photosynthesis by using enzymes to create the desired reaction.

Sokół and the team of researchers not only improved on the amount of energy produced and stored, they managed to reactivate a process in the algae that has been dormant for millennia.

She explained: “Hydrogenase is an enzyme present in algae that is capable of reducing protons into hydrogen. During evolution, this process has been deactivated because it wasn’t necessary for survival but we successfully managed to bypass the inactivity to achieve the reaction we wanted – splitting water into hydrogen and oxygen.”

Sokół hopes the findings will enable new innovative model systems for solar energy conversion to be developed.

She added: “It’s exciting that we can selectively choose the processes we want, and achieve the reaction we want which is inaccessible in nature. This could be a great platform for developing solar technologies. The approach could be used to couple other reactions together to see what can be done, learn from these reactions and then build synthetic, more robust pieces of solar energy technology.”

This model is the first to successfully use hydrogenase and photosystem II to create semi-artificial photosynthesis driven purely by solar power.

Dr Erwin Reisner, Head of the Reisner Laboratory, a Fellow of St John’s College, University of Cambridge, and one of the paper’s authors described the research as a ‘milestone’.

He explained: “This work overcomes many difficult challenges associated with the integration of biological and organic components into inorganic materials for the assembly of semi-artificial devices and opens up a toolbox for developing future systems for solar energy conversion.”

Reference: 
Katarzyna P. Sokół et al. ‘Bias-free photoelectrochemical water splitting with photosystem II on a dye-sensitized photoanode wired to hydrogenase.’ Nature Energy (2018). DOI: 10.1038/s41560-018-0232-y

​Originally published on the St John’s College website. 

In many cooperative species, the dominant breeders live longest despite the wear-and-tear of leadership and reproduction.

It has even been suggested these breeders hold the secret of immunity to age-related diseases. Some social insects, such as bees, do have breeders with genetic profiles that delay ageing – but this has never been documented in our fellow mammals.

Scientists from the University of Cambridge have now investigated the lifespans of meerkats: a highly social mammal that lives in groups of up to fifty, where a single dominant couple produce around 90% of the pups.

The researchers found that the DNA of dominant breeders actually shows signs of accelerated ageing – yet they still consistently outlive the non-breeding subordinates in the group. Their study shows that dominants live an average of 4.4 years compared to subordinates 2.8 years.

This is because meerkat underlings are forced to take the often-fatal risk of leaving the safety of the group to find breeding opportunities, say scientists. Dominants rarely tolerate rival breeders, and violently eject subordinates from the group if they feel threatened.

On reaching the top of the social pecking order, however, meerkats remain ensconced within the group. The study shows an average subordinate spends more than six days each year in the wilderness, with this figure rising year-on-year. Dominant breeders are typically absent for under two hours per year.

“Dominant meerkats typically die due to internal stresses on their bodies, resulting in gradual, predictable declines until death. In humans we might describe this as ‘natural causes’,” said Dr Dominic Cram from Cambridge’s Department of Zoology, lead author of the study published today in Current Biology.

“Subordinate meerkats die due to sudden, unpredictable circumstances such as exposure to predators, killing them instantly. A meerkat’s place within the social group shapes the mortality risks it faces,” he said.

“The secret of long life for meerkats is not to battle the inevitable declines of ageing, but to be the ruler of your community, profiting from social support and cracking down on would-be rivals.”

Cram conducted the research as part of the Kalahari Meerkat Project: a long-term study of social behavior and ecology, run for over twenty years at the University of Cambridge by Professor Tim Clutton-Brock – a leading figure in the study of mammal societies.

The project has helped train generations of zoologists through the observation of generations of meerkats, resulting in a wide range of data on the life histories of over 3000 meerkat individuals in over 100 groups.

The team collected blood samples from the meerkats, and measured DNA sections called telomeres that help protect DNA from damage – much like the plastic caps on shoe-laces. As they erode over time, the chance of unravelling increases, so the length of telomeres can be used to estimate “biological age”.

While the telomeres of subordinate meerkats remained stable, dominant telomeres shrunk by a third in just 18 months – suggesting accelerated ageing caused by the toils of raising young and fending off rivals.

Yet the dominant meerkats still lived an average of 60% longer than subordinates, as the lower ranking meerkats were increasingly forced to risk more and more time outside the group as they grew older.

“Each year the subordinates spend over triple the amount of time outside the group as the previous year, reaching a peak of 35 days per year, or 10% of their time, outside the social group,” said Cram.

For subordinate males, all females in the group are their sisters or mother, so they must court females away from the group to avoid inbreeding. Subordinate females are bullied and chased away by the dominant when they become a reproductive rival.

Of all those that leave, some return – or try to – after a few days or weeks. A lucky few start their own group and become dominant breeders. Many are never seen again.

“Within a group, a sentinel always keeps look-out and sounds the alarm, allowing the meerkats to flee into burrows or bolt-holes. Each meerkat takes a turn on sentinel duty,” said Cram.

“Away from the group there is no early warning system, and meerkats are easy prey for eagles, goshawks and caracal. Letting down their guard to dig for food is too risky, so many starve for fear of being eaten.”

“Lone meerkats have even been known to be torn apart by members of a rival group. It’s a dangerous world for a solo meerkat.”

In recent decades, exposures to environmental toxic metals such as arsenic, copper, lead, cadmium and mercury, have become a global public health concern. Although often naturally occurring, these contaminants have made their way into water supplies and, via irrigation, into the food chain. For example, in Bangladesh, deep wells were introduced in the Ganges Delta to draw water clear of bacterial and viral pathogens, but this inadvertently led to exposure to toxic metals.

Concern has often focused on the toxicity or carcinogenic properties of the metals, particularly at high doses. However, there is increasing evidence to suggest that heavy metals may have other adverse effects on health – including cardiovascular disease such as heart disease and stroke – even at lower levels of exposure, which might be prevalent in many parts of the world, including the UK and the US.

To interpret the available evidence, a team led by researchers at Cambridge’s Department of Public Health and Primary Care carried out a systematic review and meta-analysis of published studies covering 350,000 unique participants from 37 countries.

The results of the study showed that exposure to arsenic, lead, cadmium and copper – but not mercury – was associated with an increased risk of coronary heart disease and cardiovascular disease.

“It’s clear from our analysis that there’s a possible link between exposure to heavy metals or metalloids and risk of conditions such as heart disease, even at low doses – and the greater the exposure, the greater the risk,” says Dr Rajiv Chowdhury, the study’s first author. “While people shouldn’t be overly worried about any immediate health risk, it should send a message to policymakers that we need to take action to reduce people’s exposure.”

Worldwide, those at greatest exposure of arsenic, lead, cadmium and copper were around 30% to 80% more likely to develop cardiovascular disease than those at lowest exposure.

The report is important, say the researchers, because it highlights the need to tackle this environmental and public health problem, one which disproportionately affects people in low and middle income countries, though may still affect those in higher income countries. Interventions need not be costly, they stress; for example, cheap, scalable technologies (e.g. environmentally-friendly water filters) or behavioural interventions (e.g. rinsing practices of rice and vegetables prior to cooking) are currently being tested to reduce exposures at the household level.

Additionally, in a letter published at the end of June, Dr Chowdhury and colleagues expressed their disappointment that the earlier WHO report by the Independent High-Level Commission on non-communicable diseases published in June did not include exposure to heavy metals as a key contributing factor. Writing in the Lancet, the authors said: “Unfortunately, this globally important report had a major omission: recognising the detrimental role of environmental risk factors, beyond the conventional behavioural factors (tobacco and alcohol use, physical inactivity, and unhealthy diet), in enhancing global NCD burden and health inequality.”

Dr Chowdhury and colleagues recently also received £8.1 million from the UK Research Councils’ Global Challenges Research Fund to set up a long-term programme (called CAPABLE) to further investigate environmental factors of cardiovascular diseases and to help inform preventative strategies.

Reference
1) Chowdhury, R et al. Environmental toxic metal contaminants and cardiovascular risk: a systematic review 1 and meta-analysis of observational studies. BMJ; 30 Aug 2018; DOI:10.1136/bmj.k3310

2) Chowdhury R, et al. Reducing NCDs globally: the under-recognised role of environmental risk factors. The Lancet; 28 June 2018; DOI: 10.1016/S0140-6736(18)31473-9

The researchers, from the University of Cambridge, the École Nationale Supérieure des Mines and INSERM in France, implanted the device into the brains of mice, and when the first signals of a seizure were detected, delivered a native brain chemical which stopped the seizure from progressing. The results, reported in the journal Science Advances, could also be applied to other conditions including brain tumours and Parkinson’s disease.

The work represents another advance in the development of soft, flexible electronics that interface well with human tissue. “These thin, organic films do minimal damage in the brain, and their electrical properties are well-suited for these types of applications,” said Professor George Malliaras, the Prince Philip Professor of Technology in Cambridge’s Department of Engineering, who led the research.

While there are many different types of seizures, in most patients with epilepsy, neurons in the brain start firing and signal to neighbouring neurons to fire as well, in a snowball effect that can affect consciousness or motor control. Epilepsy is most commonly treated with anti-epileptic drugs, but these drugs often have serious side effects and they do not prevent seizures in three out of 10 patients.

In the current work, the researchers used a neurotransmitter which acts as the ‘brake’ at the source of the seizure, essentially signalling to the neurons to stop firing and end the seizure. The drug is delivered to the affected region of the brain by a neural probe incorporating a tiny ion pump and electrodes to monitor neural activity.

When the neural signal of a seizure is detected by the electrodes, the ion pump is activated, creating an electric field that moves the drug across an ion exchange membrane and out of the device, a process known as electrophoresis. The amount of drug can be controlled by tuning the strength of the electric field.

“In addition to being able to control exactly when and how much drug is delivered, what is special about this approach is that the drugs come out of the device without any solvent,” said lead author Dr Christopher Proctor, a postdoctoral researcher in the Department of Engineering. “This prevents damage to the surrounding tissue and allows the drugs to interact with the cells immediately outside the device.”

The researchers found that seizures could be prevented with relatively small doses of drug representing less than 1% of the total amount of drug loaded into the device. This means the device should be able to operate for extended periods without needing to be refilled. They also found evidence that the delivered drug, which was in fact a neurotransmitter that is native to the body, was taken up by natural processes in the brain within minutes which, the researchers say, should help reduce side effects from the treatment.

Although early results are promising, the potential treatment would not be available for humans for several years. The researchers next plan to study the longer-term effects of the device in mice.

Malliaras is establishing a new facility at Cambridge which will be able to prototype these specialised devices, which could be used for a range of conditions. Although the device was tested in an animal model of epilepsy, the same technology could potentially be used for other neurological conditions, including the treatment of brain tumours and Parkinson’s disease.

The research was funded by the European Union.

Reference: 
Christopher M. Proctor et al. ‘Electrophoretic drug delivery for seizure control.’ Science Advances (2018). DOI: 10.1126/sciadv.aau1291

The Open-Oxford-Cambridge AHRC DTP is a consortium of the three universities for doctoral training and funding in the Humanities. The DTP is underpinned by world-class research and training environments, supported by strategic partnerships with the BBC World Service, the National Trust and British Telecom, and is national and international in mindset, and determined to take a leading role in shaping the future of doctoral training in the UK.

The AHRC is the UK’s largest funder of postgraduate training in the arts and humanities, and plays an essential role in supporting the next generation of highly capable researchers. By working together, the AHRC, the Open University, and the Universities of Oxford and Cambridge are able to commit to investing in this partnership over its lifetime.

Professor David Rechter, incoming Director of the Open-Oxford-Cambridge AHRC DTP, said: “I am pleased by the success of our bid, and look forward to recruiting our first cohort of students next year. Supported by our partners the National Trust, the BBC World Service and British Telecom, the Open-Oxford-Cambridge DTP will offer students a wealth of opportunities to pursue research and engage in training, and to learn from each other as part of a large multi-disciplinary group. These opportunities will equip our DTP students with the research expertise and skills that will allow them to go on to wide range of careers in academia and beyond.”

Professor Martin Millett, Head of the School of Arts and Humanities at Cambridge, said: “The success of this bid is excellent news. The unique collaboration between Oxford, Cambridge and the Open University opens up exciting new prospects for the next generation of doctoral research students in the Arts and Humanities.”

Professor Edward Harcourt, the AHRC’s Director of Research, Strategy and Innovation, said: “The AHRC is delighted to announce its renewed commitment to the Doctoral Training Partnerships model. Our support for the next generation of arts and humanities researchers is critical to securing the future of the UK arts and humanities sector, which accounts for nearly a third of all UK academic staff, is renowned the world over for its outstanding quality, and which plays a vital part in our higher education ecosystem as a whole.

“We were extremely pleased with the response to our call, which saw high-quality applications from across the UK from a variety of diverse and innovative consortia, each with a clear strategy and vision for the future support of their doctoral students.”

Professor Kevin Hetherington, Pro-Vice-Chancellor (Research and Academic Strategy), The Open University, said: “The Open University is delighted that the AHRC has chosen to recognise the commitment to innovation and diversity inherent in the Open-Oxford-Cambridge DTP, and looks forward to participating fully in the delivery of an exciting training programme for our PhD students.”

Professor Karen O’Brien, Head of the Humanities Division, University of Oxford, said: “This is good news and an endorsement of our collective commitment to developing the next generation of Humanities scholars. We are looking forward to working with the Open University, Cambridge, the AHRC and our strategic partners to deliver a truly exciting opportunity to our consortium students.”

Stephen Cassidy, Chief Researcher, System Science, BT Labs, said: “As a communication company deeply rooted in the interaction between people, communities and businesses, BT sees great benefit in being part of this DTP. Interaction with the students and academics will extend our understanding of ethical, legal and social ramifications of the possible directions the industry as a whole could (and is) embarking on. These are issues of international scale, and we are pleased to link with the DTP and to provide further links with our research collaborations around the UK and the globe.”

Jamie Angus, Director, BBC World Service Group, said: “The objectives of the Consortium and the Doctoral Training partnership fit very well with the BBC World Service’s objectives; The BBC World Service Group provides independent impartial journalism to nearly 350 million people around the world each week, across cultural, linguistic and national boundaries.  We look forward to working with world-class doctoral students in the Humanities drawing on their research skills and subject expertise, as well as making the most of the huge range of languages studied at Oxford, Cambridge and the OU. Working together we will play our part so that the Consortium can provide DTP-funded students with skills and experience they need to communicate their ideas beyond academia so that they may be better able to reach a wider audience.”

Nino Strachey, Head of Research and Specialist Advice at the National Trust, said: “The National Trust is delighted at the success of the bid and excited to work with students and staff from these internationally recognised universities and partners. With a long history of hosting and co-supervising PhDs, we look forward to offering opportunities for students to gain experience of the heritage sector and to work with Europe’s largest conservation charity.”

Information on how to apply for scholarships via the Open-Oxford-Cambridge AHRC Doctoral Training Partnership for entry in 2019/20 will be available from www.oocdtp.ac.uk from 1 September 2018.

A new study shows that men only have to believe they’ve bested another man in competition to get raised testosterone levels and an inflated sense of their own value as a sexual prospect.

Scientists found that this hormonal and psychological shift made men more inclined to approach new potential partners.

The research team measured hormone levels, as well as self-perceived attractiveness and confidence in approaching women, in 38 men in their twenties before and after competing in head-to-head battles on rowing machines.

Unbeknownst to participants, the competitions in the study were rigged to randomly declare the winner, regardless of who was the stronger rower.

While previous studies have shown that winning can affect male hormones, it was not known whether this was down to the efforts it takes to win or the belief that one is victorious.

The latest study, led by biological anthropologists from the University of Cambridge and published today in the journal Human Nature, reveals that just being convinced you have won, or indeed lost, is enough to cause male hormonal fluctuations that can influence sexual behaviour.

Researchers say this is an example of “plasticity”: the body adapting quickly – without altering genetic make-up – to suit a change in circumstance. In this case a perceived change in social status, due to the men believing they have defeated a rival.

The body attempts to take advantage of this apparent status improvement by inducing chemical and consequently behavioural changes that promote a “short-term” approach to reproductive success, say the researchers. Namely, more sex with new and different partners.

“Much of evolution consists of trade-offs in energy investment,” said study lead author Dr Danny Longman, from Cambridge’s Department of Archaeology.

“A common trade-off for males both across and within species is between mating strategies. One reproductive approach is short-term, investing time and energy in attracting and pursuing many mates, and fighting off competition. Another approach is long-term, investing energy in raising offspring with a single mate.”

“We found that a perceived shift in social status can cause male physiology to adapt by preparing to shift mating strategies to optimise reproductive success.”

Longman points out that in many animal populations, male social hierarchies correspond with reproductive success, and social status is determined by competition between males.

The study used a simple proxy for social and sexual competition by pitting athletic young men against each other to see who was the most powerful rower.

“Victory in a rowing contest strongly implies the possession of greater physical strength than the opponent, a trait found to be valued by women in our evolutionary past when choosing a mate,” said Longman.

He took saliva samples to test hormone levels before and after the races. A number of psychological questionnaires were also administered, designed to gauge self-esteem, ‘sociosexuality’ (willingness to engage in casual sex), ‘self-perceived mate value’ and mating behaviour (e.g. the likelihood of approaching attractive women). Crucially, Longman and colleagues then manipulated the results of the races.

The men who believed they had won received an average testosterone increase of 4.92%, while those convinced they had lost dropped by an average of 7.24%. Overall, men who thought they were winners had testosterone levels 14.46% higher their deflated opponents.

The men who thought they had lost showed no difference in their perceived value as a mate or confidence approaching women. However, the men who felt like winners had a ‘self-perceived mate value’ that was 6.53% higher, on average, than their rivals, and were 11.29% more likely to approach attractive women in an effort to instigate sexual relations.

“The endocrine system that controls hormones is responsive to situational changes. Previous research has shown that testosterone is lower when men are in a committed relationship, or have children, to promote long-term mating strategies,” said Longman.

“Our results show that both testosterone and its corresponding psychological effects can fluctuate quickly and opportunistically, shifting towards short-term mating in response to a perceived change in status that may increase mating value.”

Male social status has less to do with physical strength in many modern societies, and Longman would be curious to see if similar results arise from intellectual challenges more familiar to the office-based culture many men now inhabit. There is always the issue of free will, however.

“Male physiology may shift to take advantage of certain situations, but ultimately a man’s decisions are up to him.”

The Icelandic Sagas tell of Erik the Red: exiled for murder in the late 10th century he fled to southwest Greenland, establishing its first Norse settlement.

The colony took root, and by the mid-12th century there were two major settlements with a population of thousands. Greenland even gained its own bishop.

By the end of the 15th century, however, the Norse of Greenland had vanished – leaving only abandoned ruins and an enduring mystery.

Past theories as to why these communities collapsed include a change in climate and a hubristic adherence to failing farming techniques.

Some have suggested that trading commodities – most notably walrus tusks – with Europe may have been vital to sustaining the Greenlanders. Ornate items including crucifixes and chess pieces were fashioned from walrus ivory by craftsmen of the age. However, the source of this ivory has never been empirically established.

Now, researchers from the universities of Cambridge and Oslo have studied ancient DNA from offcuts of tusks and skulls, most found on the sites of former ivory workshops across Europe, in order to trace the origin of the animals used in the medieval trade.

In doing so they have discovered an evolutionary split in the walrus, and revealed that the Greenland colonies may have had a “near monopoly” on the supply of ivory to Western Europe for over two hundred years.

For the latest study, published today in the journal Proceedings of the Royal Society B, the research team analysed walrus samples found in several medieval trading centres – Trondheim, Bergen, Oslo, Dublin, London, Schleswig and Sigtuna – mostly dating between 900 and 1400 CE.

The DNA showed that, during the last Ice Age, the Atlantic walrus divided into two ancestral lines, which researchers term “eastern” and “western”. Walruses of the eastern lineage are widespread across much of the Arctic, including Scandinavia. Those of the western, however, are unique to the waters between western Greenland and Canada.

Finds from the early years of the ivory trade were mostly from the eastern lineage. Yet as demand grew from the 12th century onwards, the research team discovered that Europe’s ivory supply shifted almost exclusively to tusks from the western lineage.

They say that ivory from western linage walruses must have been supplied by the Norse Greenlanders – by hunting and perhaps also by trade with the indigenous peoples of Arctic North America.

“The results suggest that by the 1100s Greenland had become the main supplier of walrus ivory to Western Europe – a near monopoly even,” said Dr James H. Barrett, study co-author from the University of Cambridge’s Department of Archaeology.

“The change in the ivory trade coincides with the flourishing of the Norse settlements on Greenland. The populations grew and elaborate churches were constructed.

“Later Icelandic accounts suggest that in the 1120s, Greenlanders used walrus ivory to secure the right to their own bishopric from the king of Norway. Tusks were also used to pay tithes to the church,” said Barrett.

He points out that the 11th to 13th centuries were a time of demographic and economic boom in Europe, with growing demand from urban centres and the elite served by transporting commodities from increasingly distant sources.

“The demands for luxury goods produced from ivory may have helped the far-flung Norse communities in Greenland survive for centuries,” said Barrett.

Co-author Dr Sanne Boessenkool of the University of Oslo said: “We knew from the start that analysing ancient DNA would have the potential for new historical insights, but the findings proved to be particularly spectacular.”

The new study tells us less about the end of the Greenland colonies, say Barrett and colleagues. However, they note that it is hard to find evidence of walrus ivory imports to Europe that date after 1400.

Elephant ivory eventually became the material of choice for Europe’s artisans. “Changing tastes could have led to a decline in the walrus ivory market of the Middle Ages,” said Barrett.

Ivory exports from Greenland could have stalled for other reasons: over-hunting can cause walrus populations to abandon their coastal “haulouts”; the “Little Ice Age” – a sustained period of lower temperatures – began in the 14th century; the Black Death ravaged Europe.

Whatever caused the cessation of Europe’s trade in walrus ivory, it must have been significant for the end of the Norse Greenlanders,” said Barrett. “An overreliance on a single commodity, the very thing which gave the society its initial resilience, may have also contained the seeds of its vulnerability.”

The heyday of the walrus ivory trade saw the material used for exquisitely carved items during Europe’s Romanesque art period. The church produced much of this, with major ivory workshops in ecclesiastical centres such as Canterbury, UK.

Ivory games were also popular. The Viking board game hnefatafl was often played with walrus ivory pieces, as was chess, with the famous Lewis chessmen among the most stunning examples of Norse carved ivory.

Tusks were exported still attached to the walrus skull and snout, which formed a neat protective package that was broken up at workshops for ivory removal. These remains allowed the study to take place, as DNA extraction from carved artefacts would be far too damaging.

Co-author Dr Bastiaan Star of the University of Oslo said: “Until now, there was no quantitative data to support the story about walrus ivory from Greenland. Walruses could have been hunted in the north of Russia, and perhaps even in Arctic Norway at that time. Our research now proves beyond doubt that much of the ivory traded to Europe during the Middle Ages really did come from Greenland”.

The research was funded by the Leverhulme Trust, Nansenfondet and the Research Council of Norway.

A team of scientists, including a volcanologist and mathematician from the University of Cambridge, discovered the phenomenon through detailed observations of gas emissions from Kīlauea volcano in Hawaii.

At many volcanoes around the world, gas emissions are monitored routinely to help with forecasting eruptions. Changes in the output or proportions of different gases – such as carbon dioxide and sulphur dioxide – can herald shifts in the activity of a volcano. Volcanologists have considered that these chemical changes reflect the rise and fall of magma in the Earth’s crust but the new research reveals that the composition of volcanic gases depends also on the size of the gas bubbles rising up to the surface.

Until the latest spectacular eruption opened up fissures on the flank of the volcano, Kīlauea held a vast lava lake in its summit crater. The behaviour of this lava lake alternated between phases of fiery ‘spattering’ powered by large gas bubbles bursting through the magma, and more gentle gas release, accompanied by slow and steady motion of the lava.

In the past, volcanic gases have been sampled directly from steaming vents and openings called fumaroles. But this is not possible for the emissions from a lava lake, 200 metres across, and at the bottom of a steep-sided crater. Instead, the team used an infrared spectrometer, which is employed for routine volcano monitoring by co-authors of the study, Jeff Sutton and Tamar Elias from the Hawaiian Volcano Observatory (US Geological Survey).

The device was located on the edge of the crater, pointed at the lava lake, and recorded gas compositions in the atmosphere every few seconds. The emissions of carbon- and sulphur-bearing gases were measured during both the vigorous and mild phases of activity.

Each individual measurement was used to compute the temperature of the volcanic gas. What immediately struck the scientists was that the gas temperatures ranged from 1150 degrees Celsius – the temperature of the lava – down to around 900 degrees Celsius. “At this temperature, the lava would freeze,” said lead author Dr Clive Oppenheimer, from Cambridge’s Department of Geography. “At first, we couldn’t understand how the gases could emerge much colder than the molten lava sloshing in the lake.”

The clue to this puzzle came from the variation in calculated gas temperatures – they were high when the lava lake was placid, and low when it was bubbling furiously. “We realised it could be because of the size of the gas bubbles,” said co-author Professor Andy Woods, Director of Cambridge’s BP Institute. “Larger bubbles rise faster through the magma and expand rapidly as the pressure reduces, just like bubbles rising in a glass of fizzy drink; the gas cools down because of the expansion.” Larger bubbles form when smaller bubbles bump into each other and merge.

Woods and Oppenheimer developed a mathematical model to account for the process, which showed a very good fit with the observations.

But there was yet another surprising finding from the gas observations from Hawaii. As well as being cooler, the emissions from the large gas bubbles were more oxidised than expected – they had higher proportions of carbon dioxide to carbon monoxide.

The chemical balance of volcanic gases such as carbon dioxide and carbon monoxide (or sulphur dioxide and hydrogen sulphide) is generally thought to be controlled by the chemistry of the surrounding liquid magma but what the new findings showed is that when bubbles get large enough, most of the gas inside follows its own chemical pathway as the gas cools.

The ratio of carbon dioxide to carbon monoxide when the lava lake was in its most energetic state was six times higher than during the most stable phase. The scientists suggest this effect should be taken into account when gas measurements are being used to forecast major changes in volcanic activity.

“Gas measurements are critical to our monitoring and hazard assessment; refining our understanding of how magma behaves beneath the volcano allows us to better interpret our observations,” said co-author Tamar Elias from the Hawaiian Volcano Observatory.

And there is another implication of this discovery – not for eruptions today but for the evolution of the Earth’s atmosphere billions of years ago. “Volcanic emissions in Earth’s deep past may have made the atmosphere more oxidising than we thought,” said co-author Bruno Scaillet. “A more oxygen-rich atmosphere would have facilitated the emergence and viability of life on land, by generating an ozone layer, which shields against harmful ultraviolet rays from the sun.”

Reference:
Clive Oppenheimer et al “Influence of eruptive style on volcanic gas emission chemistry and temperature” Nature Geoscience (2018). DOI: 10.1038/s41561-018-0194-5

​Inset image: Clive Oppenheimer in Hawaii. Credit: Clive Oppenheimer