Most people probably think of sperm as the microscopic tadpole-like things wriggling around in human semen. But there is an astonishing amount of diversity in the size, shape and number of sperm produced by male animals. In fact, despite performing the very same function in all animal species (fertilising eggs), sperm are the most diverse cells found among animals.

This diversity is a product of evolution. Every animal’s sperm has evolved to meet the needs of the individual animal that produces it. For example, new research published in Proceedings of the Royal Society B shows that the number and size of sperm produced by a mammal depends on the size of the female reproductive tract. Studying these kinds of adaptations helps us to better understand the incredible diversity we see in sperm across animal species.

Tiny animals can have massive sperm

Sperm length varies by several orders of magnitude across species, from the tiny sperm of the porcupine (0.0003 cm) to the gigantic sperm of the fruit fly (6 cm), which is more than 20 times the length of the fly. The fruit fly’s sperm looks like a wound-up ball of string that unravels once inside the female’s even longer reproductive tract.

The number of sperm produced by different animals also varies enormously. Humans produce approximately 100 million sperm per ejaculate, while rams can produce 100 billion. Groups of sperm can even work together. Sperm in some species are known to team up and form a “train” that swims faster than individual sperm.

Promiscuous females mean more sperm

Much of the variation we see in the size, shape and number of sperm produced by different species is thought to be the product of competition for fertilisation among the sperm of different males. This is a type of sexual selection, only relatively recently described, known as “sperm competition”. In species whose females mate most promiscuously, there is strong pressure on males to invest more heavily in sperm, to ensure that one of their own little soldiers is the one that wins the battle for fertilisation.

This has led to an extraordinary array of different warfare tactics. These species, in general, produce more sperm, as more soldiers on the ground gives you a numerical advantage. It may also be advantageous to produce bigger sperm, which are faster and able to outcompete the sperm of other males in the race to the eggs.

Bigger females mean smaller sperm

Sperm can also vary depending on the size and shape of the female body. To accommodate this, sperm have to be able to swim far and fast enough, to successfully reach the eggs. In general, bigger sperm swim faster, so males should produce numerous, large sperm. But males only have finite resources to allocate to sperm production and may face trade-offs.

This means that evolutionary pressure to increase sperm size will inevitably lead to a reduction in number, and vice versa. As mentioned, recent research found that among mammals, males of smaller bodied species tend to invest in fewer, larger sperm, while males of larger species tend to invest in more, smaller sperm. This is because the females of larger species have bigger reproductive tracts and so more (but smaller) sperm can spread across the greater space and have more chance of encountering an egg.

Manlier males have lower quality sperm

As sperm can be costly for the body to produce and resources are limited, males can also face trade-offs between producing sperm and other characteristics useful for reproduction. For example, species in which males invest more in big bodies and horns, or deep voices have been shown to produce less sperm.

In humans, men with more attractive voices have been shown to have worse quality sperm. It seems that males are faced with a trade-off between investing in traits that are useful for competing with rivals, or those that increase the chance of fertilising an egg. They can’t have everything.

Males can control sperm quantities

Amazingly, males seem to be able to control the amount of sperm they produce. There is evidence that males vary the amount of sperm in ejaculates, depending on the quality of the female, or the risk of sperm competition. In humans, men looking at explicit images of two males and one female (“sperm competition images”) have been shown to produce more mobile sperm than those looking at explicit images of three females.

Female animals who mate with more than one partner are also thought to have some control over the sperm that fertilises their eggs. So-called, “cryptic female choice” occurs when females use physical or chemical mechanisms to control each male’s chances of fertilisation. This is well described in a number of animal species, providing a mechanism by which females can bias the outcome of reproduction. For example, in some species, females will mate with several males and then selectively fertilise eggs with only the largest sperm or sperm from males with more compatible immune system genes.

Jacob C Dunn, Lecturer in Human Biology, University of Cambridge

This article was originally published on The Conversation. Read the original article.

The opinions expressed in this article are those of the individual author(s) and do not represent the views of the University of Cambridge.

Solomon Schechter was instantly recognisable in 1890s Cambridge. He was tall and untidily dressed, and he had an unruly red beard that matched his fiery personality. According to his friends, he seldom wore socks that matched in colour. People and conversations, Jewish history and books, were what mattered most to him.

In 1890 Schechter, a Romanian-born rabbi, became Lecturer in Talmudics at Cambridge. Together with his wife Mathilde he entertained a wide circle of people of different faiths. His Cambridge friends included the Presbyterian twin sisters, Agnes Lewis and Margaret Gibson, co-founders of Westminster College, William Robertson Smith of Christ’s, J Rendel Harris of Clare, and Charles Taylor of St John’s.

His closest friend was the reclusive James Frazer of Trinity, author of The Golden Bough, a monumental comparative study of folklore, magic and religion, who proof-read Schechter’s essays and with whom Schechter liked to take long walks.

To mark the centenary of Schechter’s death, scholars are looking afresh at his remarkable life and afterlife - in particular at the contribution to scholarship made by a man with an omnivorous hunger for learning that drove him from the traditional Jewish Eastern-European world into which he was born to Vienna, Berlin, London, Cambridge and finally New York.

When he collapsed (and later died) after giving a lecture on Jewish philanthropy, his wife recounted that he asked for a book to read, protesting that “I can’t just lie down here doing nothing”.

A conference in Cambridge on Sunday, November 22, will bring together scholars from the USA, the UK, Europe and Israel to examine many aspects of Schechter’s life – from his work on ancient, medieval and modern Jewish history to his close relationships with his Cambridge contemporaries.

“Solomon Schechter was only the second Jew to be appointed to a teaching position at Cambridge. He was the quintessential absent-minded but brilliant scholar,” says Dr Theodor Dunkelgrün of CRASSH and St John’s College, who is convening the conference.

“He possessed a phenomenal intellect and was passionately interested not just in Jewish theology and history generally, but in all manner of literary, social, and cultural issues, including the role of women in Judaism, in ways that were way ahead of his time. A dazzling intermediary between rabbinic and academic worlds, he wrote beautiful, pioneering essays for an appreciative Victorian readership.”

It was a meeting with two of his Cambridge friends that won Schechter a place in history. In May 1896, Schechter was walking along King’s Parade when he met Agnes Lewis who, with her sister Margaret Gibson, had recently returned from Cairo where they had purchased a bundle of interesting documents. Lewis and Gibson, whose remarkable lives are vividly documented in Janet Soskice’s Sisters of Sinai, were self-taught scholars who had learnt Syriac in order to be able to read the earliest known versions of the Christian gospels.

Among the documents that Lewis and Gibson had acquired from a dealer in Cairo was a grubby scrap of paper which looked, in Gibson’s words “as if a grocer had used it for something greasy”. Schechter identified this fragment as part of a medieval copy of a hitherto unknown Hebrew original of the apocryphal book known as Ecclesiasticus to Christians and the Wisdom of Ben Sira to Jews. The incredible discovery suggested to him the possibility that there might well be more where it came from.

In accordance with Jewish law, no document containing the Holy Name may be destroyed. Jewish communities collect old texts beyond use in a so-called Geniza, a tomb for texts. The precious fragment of text that had, according to Gibson, made Schechter’s eyes glitter with excitement came from such a Geniza, a vast repository of documents stored, in haphazard fashion, in the oldest of Cairo’s synagogues, the Ben Ezra.

The discovery and importance for medieval history of this unique collection is told in riveting detail by Adina Hoffman and Peter Cole’s book Sacred Trash and in Stefan Reif’s A Jewish Archive from Old Cairo.

Sponsored by his friend Professor Charles Taylor, Master of St John’s College, Schechter travelled from Cambridge to Cairo, where, after winning the trust of the chief rabbi, he entered a windowless room that contained several hundreds of thousands of documents and manuscripts accrued, layer by dusty layer over a period of nearly a thousand years.

“A battlefield of books” is how Schechter described the chaos of handwritten manuscripts mingled with later printed text. Extraordinary as it may now seem, the chief rabbi authorised Schechter to take as much as he liked to deposit in Cambridge University Library. Schechter famously commented that he liked it all.

After spending a month trying to separate out the early material which mattered to him most, Schechter packed a “whole mass of rugged, jumbled, dirty stuff into huge sacks” which were dispatched to Cambridge. A black-and-white photograph reproduced in Sisters of Sinai shows Schechter sitting in a room in the old University Library surrounded by boxes brimming over with documents that range from love letters and children’s doodles to hymns and religious texts.

Today these 193,000 manuscript fragments make up the Taylor-Schechter Genizah Collection in the Cambridge University Library – a treasure trove that an ambitious digitisation project has recently made accessible to scholars worldwide.

Schechter is not surprisingly best remembered for his contribution to the preservation of an archive that offers a unique window onto daily life of the medieval Jewish past in the Islamic world. But his pioneering study of the Geniza was just one strand in a career that took him from the Hassidic milieu of the small Romanian town where he was born to the rarefied world of late-Victorian Cambridge, and eventually to America.

In 1902, Schechter left Cambridge to take up the chancellorship of the Jewish Theological Seminary of America in New York, where he helped shape a generation of scholars and communal leaders and became the unintentional founder of the movement now known as Conservative Judaism.

Dunkelgrün says: “Schechter’s name will always, and justly, be associated with the Geniza, but he was much more than a Geniza scholar – he was a polymath who cared passionately for the entirety of the Jewish tradition, mystical and rational, from antiquity to his own time and beyond, towards the future. He paired this panoramic vision both with the traditional rabbinical education he received at home, in Lemberg and in Vienna, and with the philological skills he acquired in Berlin to produce critical editions of several major Rabbinic texts.”

 A postdoctoral research fellow at CRASSH,  Dunkelgrün is contributing to a European Research Council-funded project on The Bible and Antiquity in 19^th-century culture. He insists that Schechter’s work in Cambridge over a period of 20 years was made possible in large part because of the fascination of Victorian England, and Cambridge in particular, for biblical antiquity.

“Schechter cut an exotic figure, but one that was strangely at home in academic circles already convinced about the importance of rabbinic studies for the early history of Christianity. Schechter was the second in a line of six teachers of Rabbinics at Cambridge, the last of whom was Professor Nicholas de Lange, now formally retired from his post. We hope very much that this conference will draw attention not only to Schechter but also to this unique and precious tradition of Cambridge scholarship, and the importance of keeping it alive.”

Attendance at Sunday’s conference, Solomon Schechter’s Life and Legacy, is free of charge. Particulars and a link to registration may be found here: http://www.crassh.cam.ac.uk/events/26067

Inset images: Solomon Schechter, before his death in 1915 (Wikimedia Commons); Solomon Schechter at work in the old University Library (Reproduced by kind permission of the Syndics of Cambridge University Library).

Madagascar is one of the world’s great biodiversity hotspots, having been isolated from major continents for millions of years. The country has a great diversity of habitats, and its flora and fauna have evolved into unique species, including some of the world’s most iconic species, such as lemurs and baobabs. Madagascar’s marine environment – in particular its mangroves and coral reefs – also has global significance.

As with biodiversity in much of the world, Madagascar’s habitats, animals and plants are under threat from a number of different factors, particularly deforestation and the illegal wildlife trade. However, President Rajaonarimampianina has a strong track record on tackling issues of conservation, including having trebled marine protected areas.

A key part of the President’s visit was to the Cambridge Conservation Initiative (CCI), where he took part in a roundtable discussion with experts on Madagascar from the CCI and external conservation bodies. He opened the roundtable with a speech in which he outlined his vision for biodiversity conservation and how it fits into and supports the wider sustainable development of the country, highlighting challenges where he feels the University of Cambridge and the wider UK-based conservation community might be of greatest value in supporting the government and people of Madagascar in addressing these challenges.

Dr Mike Rands, Executive Director of the Cambridge Conservation Initiative, said: “Madagascar is an extremely important country from a biodiversity perspective and President Rajaonarimampianina has a strong track record on tackling the conservation challenges faced by his country. We look forward to learning from his knowledge and experience and sharing our own expertise to find ways to help address these challenges.”

A number of CCI partners have strong links to Madagascar, with many having been involved in building the capacity of conservation researchers and NGOs within the country for a number of years. Representatives from Fauna & Flora International, IUCN, BirdLife International and the Tropical Biology Association, the Durrell Wildlife Conservation Trust and Blue Ventures were also involved in the roundtable discussion.

Each year, Cambridge hosts the Student Conference on Conservation Science, which attracts 200 young researchers from around 60 countries, and provides bursaries and internships for around 30 scientists from low- and middle-income countries. The number of delegates from Madagascar has grown rapidly: the first delegates began attending in 2001, but in March 2016 one in ten of all talks will be by a Madagascan delegate.

The new analysis, recently published by the Joseph Rowntree Foundation (JRF) and conducted by researchers at the Cambridge Centre for Housing and Planning Research (CCHPR) in the Department of Land Economy, is the first to look at the impact of building replacements homes as shared ownership.

The report, Understanding the likely poverty impacts of the extension of Right to Buy to housing association tenants, estimates that there will be 75,000 fewer low-cost homes becoming available to let over the next 5 years if the homes built to replace those sold are available as shared ownership rather than as low-cost rentals.

Taking into account the incomes of social tenants, the affordability of homes and the take-up rate of Right to Buy (RTB) by council tenants, researchers predict that 128,000 Housing Association tenants are likely to buy their homes under RTB over the next 5 years – fewer than one in 10 of all tenants.  

The research shows that there are currently around 180,000 housing association tenants who could afford to exercise their RTB. Around half of these will be required to pay higher rents under the Governments new Pay to Stay scheme, and the higher rents they will face are likely to encourage them to buy their homes if possible.

The policy will have a huge impact on people who need to access low cost rented homes in the future, say the JRF. Building replacement homes for sale as shared ownership will mean that people seeking a social rented home will be pushed into the bottom end of the private rented sector, where homes are typically more expensive, less secure and in worse condition than Housing Association homes. The report finds that over the next five years if replacement homes are built for sale:

• 62,000 tenants will have to find an average of £1,668 extra a year to pay private rent. Around a third of these households are paying their rent themselves from their generally low earnings.
• The other two thirds are in receipt of housing benefit, meaning that £31 million will be added onto the housing benefit bill as more people who claim housing benefit are pushed into the more expensive private rented sector or remain longer in homeless accommodation.
• Just three percent of new social tenants could afford to buy the replacement properties if they were available as shared ownership.

In contrast, if the homes are built back at the same rent levels as those lost, there is only a temporary loss of lettings – caused by the delay whilst replacement housing is built. Under this scenario the estimated housing benefit costs of the policy fall to around £16 million and the increase numbers renting privately or in homeless accommodation is close to zero by the end of five years. The number of available lettings will increase after five years as new rented homes continue to be built.

The replacement homes will be funded by the sale of high-value council homes, likely to be classified as homes that are valued in the top third regionally. Local Authorities have different proportions of high value housing stock, meaning that some face losing a large amount of their social housing, while others will be forced to sell very little, or own none to start with. The five worst affected areas are all in the London commuter belt, and face losing more than half of all their low-cost lettings.

“The research has shown that the rent level of replacement stock is critical. Replacement homes for sale or shared ownership will not be affordable to those seeking social rented housing,” said Anna Clarke, Senior Research Associate at CCHPR.

“Replacement on a like-for-like basis could have a positive impact on the availability of social lettings, over the next five to ten years, though in the long term the subsidy for Right-to-Buy discounts cannot forever be found by selling off high value council stock without continually stretching the definition of high value,” she said.

Julia Unwin, Chief Executive of the JRF, said that this research shows how important it is to keep up the numbers of genuinely affordable rented homes.

“To make sure that this policy doesn’t drive up poverty in the long term, the Government must ensure that every low-rent home sold is replaced by another of the same tenure, same cost and same locality,” said Unwin.

Adapted from a Joseph Rowntree Foundation press release. 

The GSK/Cambridge Strategic Partnership builds on collaborations between the partners that bring together a variety of unique and complementary expertise and capabilities, from basic biology through to clinical studies, which when combined could transform how we develop the next wave of ‘game-changing’ medicines.

At an event being held at Trinity Hall, University of Cambridge, to celebrate the partnership, researchers from all three organisations will be showcasing existing projects, which include research towards new medicines for brain trauma, cystic fibrosis, osteoarthritis and chronic obstructive pulmonary disease (COPD), and the development of cutting-edge imaging techniques.

So far, the partnership has brought together scientific and clinical experts and provided access to research infrastructure across the university and hospital, including that provided by the NIHR Biomedical Research Centre. This has led to a growing range of active collaborations, including pre-clinical and clinical research projects, studentships and post-doctoral appointments, training and education, drug discovery workshops and a Knowledge Exchange Programme. The partners are looking at ways of building stronger links between their respective programmes focused on Africa and on the search for new medicines for neglected tropical diseases.

Professor Patrick Maxwell, Regius Professor of Physic at the University of Cambridge, says: “Our vision for the Cambridge Biomedical Campus is to pursue world-leading biomedical research and translate this into new or improved diagnostics and treatments. Key to this vision are partnerships with industry.

“Our collaboration with GSK builds on the strengths of each partner to create a relationship that is far greater than just the sum of its parts. It gives our academics access to the technologies and molecules that only industry can provide while giving GSK access to the world-leading research knowledge at Cambridge, delivering valuable impact for both partners.”

The relationship champions the value of industry-academia collaboration to build trust and enable scientists to share complementary skills and expertise. A GSK ‘Entrepreneur in Residence’ to the university provides support to academics to encourage translational thinking. By supporting academics in their applications to translational funding programmes, GSK seeks to leverage its investment and grow the partnership further.

A Varsity Funding Programme, overseen by a Joint Steering Committee and part of the Strategic Partnership, directly funds collaborative projects focused on developing new medicines across the breadth of GSK research areas of interest, such as small molecules, biopharmaceuticals and cell/gene therapy. In addition to this core focus the Varsity programme also supports enabling/fundamental scientific projects which aim to address clear gaps in our understanding of disease and drug mechanisms.

Experimental Medicine

A key component of the partnership is a more targeted approach to testing medicines in patients known as ‘experimental medicine’. Early stage R&D has, until very recently, been limited to lab and animal-based research. As a result, it has been very difficult to accurately identify new targets and to measure the impact of potential new medicines on disease; in recent years, only around 10% of compounds entering clinical trials have succeeded. With recent technological advances, it is now possible to examine how different diseases behave in individual cells in the body, and the impact of potential new medicines on disease processes.

For example, a collaboration between Professor Andres Floto at the University of Cambridge and Papworth Hospital NHS Foundation Trust and Dr Rab Prinjha at GSK is looking at a potential new treatment for inflammatory lung disease. The team is using state-of-the-art remote monitoring devices to study precisely how certain inflammatory molecules affect the symptoms of disease in a small group of patients. If this small study suggests they are effective in reducing the chemical signs of the disease, then a larger, more expensive clinical trial may be justified. If, on the other hand, the results are negative, the expense, time and impact on patients of a clinical trial can be spared.

Paul-Peter Tak, Head of Immuno-Inflammation at GSK and a lead on the Cambridge partnership, says: “At GSK, we believe that working alongside scientists from outside our labs is crucial to strengthening our understanding of human disease. The scientific community needs to embrace collaboration and share information about its successes and failures if we’re to accelerate the development of new treatments for patients.

“Our partnership with Cambridge University is a great opportunity for us to combine our drug development expertise with the research skills of the academic scientists based at this world leading hub for life sciences research. Centred around our own clinical trials unit located within the city’s main hospital, we’re perfectly placed to work together to translate cutting edge early stage science in to innovative new medicines.”

In a study published in the Journal of Psychiatric Research, researchers also report that sex addicts are more susceptible to environment ‘cues’ linked to sexual images than to those linked to neutral images.

Sex addiction – when an individual has difficulty controlling their sexual thoughts, feelings or behaviour – is relatively common, affecting as many as one in 25 young adults. It is heavily stigmatised and can lead to a sense of shame, affecting an individual’s family and social life as well as their work. There is no formal definition of the condition to help with diagnosis.

In previous work led by Dr Valerie Voon from the Department of Psychiatry at the University of Cambridge, scientists found that three brain regions were more active in sex addicts compared with the healthy volunteers. Significantly, these regions – the ventral striatum, dorsal anterior cingulate and amygdala – were regions that are also activated in drug addicts when shown drug stimuli.

In the new study, funded by the Wellcome Trust, Dr Voon and colleagues studied the behaviour of 22 sex addicts and 40 ‘healthy’ male volunteers undergoing tasks. In the first task, individuals were shown a series of images in pairs, including naked women, clothed women and furniture. They were then shown further image pairs, including familiar and new images, and asked to choose an image to ‘win £1’ – although the participants were unaware of the odds, the probability of winning for either images was 50%.

The researchers found that sex addicts were more likely to choose the novel over the familiar choice for sexual images relative to neutral object images, whereas healthy volunteers were more likely to choose the novel choice for neutral human female images relative to neutral object images.

“We can all relate in some way to searching for novel stimuli online – it could be flitting from one news website to another, or jumping from Facebook to Amazon to YouTube and on,” explains Dr Voon. “For people who show compulsive sexual behaviour, though, this becomes a pattern of behaviour beyond their control, focused on pornographic images.”

In a second task, volunteers were shown pairs of images – an undressed woman and a neutral grey box – both of which were overlaid on different abstract patterns. They learned to associate these abstract images with the images, similar to how the dogs in Pavlov’s famous experiment learnt to associate a ringing bell with food.  They were then asked to select between these abstract images and a new abstract image.

This time, the researchers showed that sex addicts where more likely to choose cues (in this case the abstract patterns) associated with sexual and monetary rewards. This supports the notion that apparently innocuous cues in an addict’s environment can ‘trigger’ them to seek out sexual images.

“Cues can be as simple as just opening up their internet browser,” explains Dr Voon. “They can trigger a chain of actions and before they know it, the addict is browsing through pornographic images. Breaking the link between these cues and the behaviour can be extremely challenging.”

The researchers carried out a further test where 20 sex addicts and 20 matched healthy volunteers underwent brain scans while being shown a series of repeated images – an undressed woman, a £1 coin or a neutral grey box.

They found that when the sex addicts viewed the same sexual image repeatedly, compared to the healthy volunteers they experienced a greater decrease of activity in the region of the brain known as the dorsal anterior cingulate cortex, known to be involved in anticipating rewards and responding to new events. This is consistent with ‘habituation’, where the addict finds the same stimulus less and less rewarding – for example, a coffee drinker may get a caffeine ‘buzz’ from their first cup, but over time the more they drink coffee, the smaller the buzz becomes.

This same habituation effect occurs in healthy males who are repeatedly shown the same porn video.  But when they then view a new video, the level of interest and arousal goes back to the original level. This implies that, to prevent habituation, the sex addict would need to seek out a constant supply of new images. In other words, habituation could drive the search for novel images.

“Our findings are particularly relevant in the context of online pornography,” adds Dr Voon. “It’s not clear what triggers sex addiction in the first place and it is likely that some people are more pre-disposed to the addiction than others, but the seemingly endless supply of novel sexual images available online helps feed their addiction, making it more and more difficult to escape.”

Reference
Banca, P et al. Novelty, conditioning and attentional bias to sexual rewards. Journal of Psychiatric Research; published in advance 27 October 2015

The V-3 “supergun” was meant to win the war for Germany. In 1943, for the first time since World War II began, Hitler was on the back foot. Allied bombs were devastating German cities and the Fuhrer was rattled. His proposed V-3 cannon would be the biggest gun the world had seen.

The V-3 was built in a truly enormous bunker buried deep in a chalk hill in northern France. Millions of tonnes of rock were excavated by hand and among the workers were hundreds of slave labourers. In its original conception, 25 barrels were to point at London – about 100 miles away – delivering up to one bomb per minute and to create an environment of fear that would turn the course of the war back in Hitler’s favour. And it was a doomed secret “drone” mission to destroy the V-3 that led to the death of Joe Kennedy Junior, a pilot and older brother of the future US president, John F. Kennedy.

The workings of the German supergun remain something of a mystery, because so much of it was destroyed and so few photographs and documents have survived. We estimated that a projectile reaching London must achieve speeds in excess of 1,500 metres per second. Each barrel of Hitler’s gun was 130 metres long, inclined at 50 degrees and we worked out that this is the perfect angle to reach London - they seem to have got it right.

The projectile was to be accelerated by means of a sequence of charges along the barrel. Precise timing of these additional charges was very important and it has been supposed that this was done electrically. In our research for a TV documentary on Channel Four, PBS Nova and National Geographic International, we found no evidence for this. Photographs from the time have no sign of electrical wiring or triggering devices and our own experiments suggest that the charges were triggered by the heat of the advancing gas behind the projectile.

Hitler’s engineers had great difficulty perfecting the all-important timing, we think because of leakage of hot gas past the seal behind the projectile. They encountered other problems with their design, particularly to perfect a shape of projectile that would be aerodynamic at supersonic speeds. It had to remain stable without the benefit of spin (the barrel was not rifled) but in early tests the projectile was found to tumble uncontrollably. This problem was never solved, as far as we know. The Allies knew nothing of the supergun until Canadian forces overran the site after D-Day. But they knew that for the Germans to be expending that many resources on the site – they were certainly up to no good.

It wasn’t easy to see how to destroy the supergun. The Americans planned to attack the installation with a “drone” (not known by that name back then) which was a remote-controlled heavy bomber packed with 12 tonnes of high explosives. The idea was to crash the unmanned aircraft directly into the site at Mimoyecques, near Calais. The mission, code named Project Anvil, ended badly.

The Joe Kennedy Jr mission

Joe Kennedy Junior was piloting a B-24 Liberator on August 12 1944. He and co-pilot Wilford Willy were supposed to take the plane up to cruising altitude, set the correct course and bail out. A second aircraft flying nearby was to take over the controls (aided by a primitive television transmission system). But completely without warning, the plane exploded over Blythburgh in Suffolk only 20 minutes after it had taken off. Kennedy and Willy were killed and their bodies never found, such was the violence of the explosion.

The circumstances of Kennedy’s death weren’t well known for the best part of 70 years. Recent documents have been found that show that the bomb-arming mechanism was flawed and that efforts to make it safe only exacerbated the hazards. In our documentary we show that solenoids – a type of electromagnet – used for arming the bombs were likely to have overheated causing premature detonation.

This tragedy was all in vain. Unknown to the allies at the time, the complex at Mimoyecques had been abandoned after it was successfully destroyed in a bombing raid on July 6 1944. British engineer Barnes Wallis, the brains behind the bouncing bomb, had developed the Tallboy bomb. Dropped from a height of 15,000ft it was designed to bury itself deep into the chalk and to trigger a small earthquake. Eight Tallboys hit the supergun site and the network of tunnels and the foundations, bunkers and munitions stores were all damaged beyond repair.

The genius of Barnes Wallis cannot be overstated. He had worked out the right shape for the nose cone of the Tallboy so that it would remain aerodynamic while approaching the speed of sound and at the same time being strong enough to penetrate 15 metres underground. He discovered that if the fins were tilted by only 5 degrees the bomb would spin, stabilising it in flight.

It is unlikely that the supergun would ever have been a successful game-changing weapon, even if the Normandy landings had failed. The numerous technical challenges of the gun itself were proving difficult to resolve but perhaps more importantly a fixed gun installation is an easy target. If it hadn’t been the Tallboys of July 6, or the ill-fated Kennedy mission of August 12, then the installation at Mimoyecques would have been destroyed one way or another before it could do much damage to London.

But from a purely engineering perspective I’m sorry that it was never test-fired (though it’s hard to imaging how to do that safely!) I would like to have seen it work. What an amazing contraption.

Hugh Hunt, Reader in Engineering Dynamics, University of Cambridge

This article was originally published on The Conversation. Read the original article.

The opinions expressed in this article are those of the individual author(s) and do not represent the views of the University of Cambridge.

Most of the fat cells in the body act to store excess energy and release it when needed but some types of fat cells, known as brown adipocytes, function primarily for a process known as thermogenesis, which generates heat to keep us warm. However, an international team of researchers from the Wellcome Trust-Medical Research Council Institute of Metabolic Sciences at the University of Cambridge, UK, and Toho University, Japan, have shown that a protein found in the body, known as sLR11, acts to suppress this process.

Researchers investigated why mice that lacked the gene for the production of this protein were far more resistant to weight gain. All mice – and, in fact, humans – increase their metabolic rate slightly when switched from a lower calorie diet to a higher calorie diet, but mice lacking the gene responded with a much greater increase, meaning that they were able to burn calories faster.

Further examinations revealed that in these mice, genes normally associated with brown adipose tissue were more active in white adipose tissue (which normally stores fat for energy release). In line with this observation, the mice themselves were indeed more thermogenic and had increased energy expenditure, particularly following high fat diet feeding.

The researchers were able to show that sLR11 binds to specific receptors on fat cells – in the same way that a key fits into a lock – to inhibit their ability to activate thermogenesis. In effect, sLR11 acts as a signal to increase the efficiency of fat to store energy and prevents excessive energy loss through unrestricted thermogenesis.

When the researchers examined levels of sLR11 in humans, they found that levels of the protein circulating in the blood correlated with total fat mass – in other words, the greater the levels of the protein, the higher the total fat mass. In addition, when obese patients underwent bariatric surgery, their degree of postoperative weight loss was directly proportional to the reduction in their sLR11 levels, suggesting that sLR11 is produced by fat cells.

In their paper the authors suggest that sLR11 helps fat cells resist burning too much fat during ‘spikes’ in other metabolic signals following large meals or short term drops in temperature. This in turn makes adipose tissue more effective at storing energy over long periods of time.

There is growing interest in targeting thermogenesis with drugs in order to treat obesity, diabetes and other associated conditions such as heart disease. This is because it offers a mechanism for disposing of excess fat in a relatively safe manner. A number of molecules have already been identified that can increase thermogenesis and/or the number of fat cells capable of thermogenesis. However to date there have been very few molecules identified that can decrease thermogenesis.

These findings shed light on one of the mechanisms that the body employs to hold onto stored energy, where sLR11 levels increase in line with the amount of stored fat and act to prevent it being ‘wasted’ for thermogenesis.

Dr Andrew Whittle, joint first author, said: “Our discovery may help explain why overweight individuals find it incredibly hard to lose weight. Their stored fat is actively fighting against their efforts to burn it off at the molecular level."

Professor Toni Vidal-Puig, who led the team, added: “We have found an important mechanism that could be targeted not just to help increase people’s ability to burn fat, but also help people with conditions where saving energy is important such as anorexia nervosa.”

Jeremy Pearson, Associate Medical Director at the British Heart Foundation (BHF), which helped fund the research, said: “This research could stimulate the development of new drugs that either help reduce obesity, by blocking the action of this protein, or control weight loss by mimicking its action. Based on this promising discovery, we look forward to the Cambridge team’s future findings.

“But an effective medicine to treat obesity, which safely manages weight loss is still some way off. In the meantime people can find advice on healthy ways to lose weight and boost their heart healthy on the BHF website.”

The study was part-funded in part by the British Heart Foundation, the Wellcome Trust, the Medical Research Council and the Biotechnology and Biological Sciences Research Council.

Reference
Whittle, AJ, Jiang, M, et al. Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans. Nature Communications; 20 November 2015

The first study to link precolonial African leadership and current levels of deforestation has shown a strong correlation between areas with historic leadership structures more susceptible to corruption and higher rates of forest loss today.

The study suggests that a “legal pluralism” exists across large parts of Africa where many local leaders continue to hold sway over natural resources through precolonial “traditional authority”; old power often not recognised by the state.  

By using satellite image data from 2000 to 2012 and analysing it in combination with historical anthropological data, researchers found a relationship between high deforestation and precolonial succession rules of ‘social standing’: village heads appointed through wealth or status rather than for example hereditary lineage or democratic election.

Those areas with ‘social standing’ leaderships in precolonial times have approximately 50% more deforestation than the average rate of forest loss for Africa over this period.

Leaders who draw on traditional authority are often vested with resource control rights by local communities, regardless of whether the state recognises these rights. The study’s authors say that those local leaders who can claim power through their own influence – or ‘social standing’ – are more likely to use natural resources to leverage short-term economic gains. 

The research team, from the University of Cambridge’s Department of Land Economy and its Centre for Development Studies, cite cases of loggers providing gifts such as motorcycles and paying traditional leaders to secure ‘logging permits’, despite the leaders having no state authority to grant them.

They say the findings suggest that conservationists need to go beyond state law and engage with local leaders who, despite having no apparent authority, may have a vital influence over Africa’s shrinking forests and biodiversity. The study has been published in the Journal of Land Use Policy.

“This work highlights the importance of legal pluralism in relation to deforestation in Africa, and should encourage those who want to conserve Africa’s remaining forests to look below the surface of state law to where resource use decisions are actually made: at the local level by leaders who often have little or no state authority,” said Dr Shaun Larcom who conducted the study with Cambridge colleagues Dr Terry van Gevelt and Dr Aiora Zabala.

“While such a shift in focus undoubtedly increases the complexity of research and of the policy agenda, it may actually be necessary if we want to make meaningful inroads into deforestation in Africa and the rest of the developing world,” he said.

While most of Africa’s remaining forests are protected, owned and managed by the state, rapid deforestation continues, despite ongoing international efforts aimed at state capacity building and reducing official corruption.

Over the period from 2000 to 2012 Africa lost approximately 18 million hectares of its forests. However, when these losses are broken up into ethnic boundaries that existed prior to European colonisation, the rate of deforestation varies considerably in relation to the type of local governance structure formerly in place, says study co-author Dr Zabala.

“African countries are among the ones with fastest acceleration of deforestation worldwide. Complex governance legacies pose a major challenge for the implementation of policies to address forest loss,” Zabala said.

The most common precolonial leadership structure was hereditary succession. Other structures used as base cases for the analysis were local leaders elected from above and those elected democratically.

But it was the analysis of leadership appointment through social standing that proved most distinctive, with 0.8 percentage points more deforestation compared to base cases. Compared to an average loss of 1.6 percentage points over the same period, this suggests that these regions have around 50% higher than average deforestation rates.

Social standing is “appointment by age, seniority, influence, wealth or social status”, says Dr van Gevelt. “In practice, this means that those with the most power can claim local leadership, and consequently secure further control over local natural resources,” he said. Ethnic groups where these practices occurred in precolonial times include the Kabre people of Benin and the Isoko people of Nigeria. 

The researchers suggest that there are likely to be more ownership disputes in these areas, where the legitimacy of local leaders is weaker and more ‘up for grabs’ than in an hereditary power structure, for example. Leaders from ‘social standing’ areas may grant logging access to forests to raise funds for what Larcom describes as “patrimonial largesse”: the need to give generously to the local community in order to retain social standing, and consequently leadership.

“Acknowledging the reality of legal pluralism – where both the state and non-state authorities, often with different sources of authority, compete in the same regulatory space – and the importance of non-state regulators, both as a force for good and harm in relation to deforestation in Africa, might be the missing link needed for halting large scale deforestation in Africa,” added Larcom.

“In addition to focusing on state corruption, those wishing to halt rapid deforestation also need to focus on non-state corruption.” 

Professor Lalita Ramakrishnan shares her workspace at the Laboratory of Molecular Biology (LMB) with thousands of tiny stripy fish. Zebrafish have long been a favourite in domestic aquariums: they are strikingly pretty and constantly on the move. The zebrafish at the LMB, each one no bigger than your little finger, are helping Ramakrishnan and her colleagues to find novel ways of preventing and treating tuberculosis (TB). We asked her about her work.

Why are zebrafish such good models for scientists?

Around 40 years ago scientists began to realise that zebrafish, as vertebrates, could tell us a lot about human development and human diseases. This discovery represented a real breakthrough in terms of what could be achieved using zebrafish in laboratories.

There are two key reasons why zebrafish, in particular, are so valuable. Firstly, when the new fish hatches as a tiny larva, it is optically transparent for the first two weeks of its development. This transparency means that, using powerful imaging technology, we are able to observe in real time the development of the organism as it grows to maturity. In our laboratory, we exploit the optical transparency to directly look at how the tuberculosis bacteria cause disease.

The second reason why zebrafish is such a good model is that a single mating can produce hundreds of eggs – and female zebrafish are capable of producing a new batch of eggs each week. So we have access to large numbers of animals for the work. On top of all this, zebrafish are relatively straight-forward to keep and easy to breed.

We can also create zebrafish with different mutations and we can then assess the impact of host genes on the course of disease. This kind of fundamental work enables us to identify, by a process of deduction and elimination, what genes do – which is essential to developing new medical interventions.

But surely zebrafish and humans have little in common – we’re not fish!

Humans and fish are much more alike than people might suppose – even though we diverged from our last common ancestor at least 300 million years ago. Most of the genes found in fish are also found in humans – and most of the genes that cause disease in fish also cause disease in humans. The human immune system, which fights off disease, is a lot like the immune system of fish.

My research is focused on tuberculosis in humans – a disease that affects millions of people worldwide. Without treatment, TB can be life threatening. We tend to associate human TB with the lungs, and of course fish don’t have lungs. TB does affect the lungs but it can affect almost all our organs. In humans, some 40% of TB infection is not in the lungs but elsewhere in the body - brain, bone, kidney, intestine, reproductive organs.

Fish are affected by a close relative of the human TB bacterium. If we can work out how TB works in fish, and how to prevent it and treat it in fish, then we’re a step closer to solving a major health problem in humans.

What is the life of a laboratory zebrafish like?

Our fish live in tanks that are kept pristine by a unit that cleans and circulates the water. We grow the food they need in the lab – it’s a kind of brine shrimp. Putting this live food into the tanks allows the fish to hunt for their food, creating a more natural environment for them. Zebrafish are sociable creatures so we keep them in groups. All our fish are on a programme of 16 hours of daylight and eight hours of night. This routine mimics, as much as possible, the natural environment in the regions of the world where they live. We make sure that they are as healthy and stress-free as possible. Happy fish are healthy fish – and the other way round! 

You can identify the males from the females by the roundness of the female’s belly.  When we want a new batch of eggs, we put a male and a female in a tank overnight, with the two fish separated by a transparent divider. When daylight comes, the two fish become excited and we take out the divider and they mate.  When the eggs are laid, they fall through a fine grill that enables us to take them out of the tank.

All these procedures are done as carefully as possible so as not to harm the fish or eggs.

How do you use the zebrafish eggs?

In my laboratory, we’re studying TB so we need to infect some of the fish eggs, one by one, with bacteria so that we can observe what happens.  This procedure is carried out under a microscope using a very fine needle that is hollow, enabling tiny amounts of bacteria to be delivered into the egg. Because zebrafish eggs are so tiny, it takes a while to learn how to do this. It requires good hand-eye coordination and a steady hand – but everyone learns to do it with time and practice. 

Once the eggs are infected we put them into small dishes where we can observe them. Because the eggs and the larvae are transparent, we can observe the process by which the bacteria enters the cells – and we can watch what happens as the bacteria and immune system face off.  By using fluorescence, we can colour the host (the organism affected by the disease) and the bacteria so that it’s easier to track what’s happening on a cellular level. We can, for example, observe how exactly bacteria invade and spread.

How is your work with fish helping to develop better ways of tackling TB?

At the moment, TB in the human population is treated with a long course of strong antibiotics – it often takes as long as six months to get rid of it. Strains of drug-resistant TB have developed, partly because people do not finish the courses of drugs prescribed to them.  

The work that my colleagues and I are doing suggests that there could be another, and perhaps more effective, approach to tackling TB.  Rather than only targeting the bacteria, which are so clever in their invasive strategies, it might be better to additionally target the host and help the immune system to fight it off. We might do this by boosting or tweaking the immune system.

We now need to put to the test our ideas for helping the immune system by trying out a list of available drugs – and, in the initial stages of the research, we will be using zebrafish as models.

What’s the future for zebrafish as a model organism in research?

The world of research using zebrafish is wonderfully collaborative and fast-moving.  Our main partner is the Sanger Institute which is just a few miles from the LMB.  We collaborate closely with the scientists there on tools and techniques – including producing the mutants in order to identify genetic pathways.

Zebrafish are still relatively new in terms of their contribution to research – but it’s difficult to overstate how important they are.  Every research organism has its limitations, of course. However, there’s much, much more we can learn from zebrafish that will benefit humans in the future.

This is the last article in the Cambridge Animal Alphabet series. If you have missed the others, you can catch up on Medium here.

Inset images: A two day old transgenic zebrafish embryo (Wikimedia Commons / IchaJaroslav); Zebrafish embryos (Wikimedia Commons / Adam Amsterdam, Massachusetts Institute of Technology).

The Vice-Chancellor, Sir Leszek Borysiewicz, said: “This is fantastic news. The Cavendish is and will serve as a national asset, to the benefit of research both in Cambridge and across the UK.

“This announcement demonstrates the Government’s commitment to regional and national scientific growth and innovation. It presents a major opportunity for us to create a world-leading facility in the heart of the greater Cambridge high-tech cluster and deliver a step-change in physical science research capability in the UK.”

Professor Andy Parker, Head of the Cavendish Laboratory, said: “Thanks to this welcome announcement we look forward to working with partners in Government and industry and other universities to further the globally important research which this department undertakes.

“The Cavendish Laboratory has an extraordinary history of discovery and innovation in physics since its opening in 1874, including the determination of the double-helix structure of the DNA molecule by Francis Crick and James Watson. This funding allows us to continue the tradition of innovation and originality that has been at the heart of the laboratory's programme since its foundation.”

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 University of Cambridge, UK, Northeastern University, 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 University 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 University have shed new light on how constraints in the brain limit our peripheral vision.

The 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. The 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. The 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.

The 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. The 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.”

The 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

Cambridge researchers have developed a new type of head-up display for vehicles which is the first to use laser holographic techniques to project information such as speed, direction and navigation onto the windscreen so the driver doesn’t have to take their eyes off the road. The technology – which was conceptualised in the University’s Department of Engineering more than a decade ago – is now available on all Jaguar Land Rover vehicles. According to the researchers behind the technology, it is another step towards cars which provide a fully immersive experience, or could even improve safety by monitoring driver behaviour.

Cars can now park for us, help us from skidding out of control, or even prevent us from colliding with other cars. Head-up displays (HUD) are one of the many features which have been incorporated into cars in recent years. Alongside the development of more sophisticated in-car technology, various companies around the world, most notably Google, are developing autonomous cars.

“We’re moving towards a fully immersive driver experience in cars, and we think holographic technology could be a big part of that, by providing important information, or even by encouraging good driver behaviour,” said one of the technology’s developers, Professor Daping Chu of the University’s Department of Engineering, who is also Chairman of the Centre for Advanced Photonics and Electronics (CAPE).

CAPE was established in 2004 to enable Cambridge researchers to work in partnership with industry to translate science into new technologies and products. The holographic HUD technology originated with Professor Bill Crossland in 2001, and was licensed to and developed by CAPE partner company Alps Electric, and then by Two Trees Photonics Ltd at Milton Keynes, in collaboration with researchers at CAPE. Products were designed by Two Trees Photonics and Alps, and manufactured by Alps for Jaguar Land Rover. The HUD became an available option on their vehicles in September 2014.

The HUD technology developed at Cambridge is the first to use laser holographic techniques, which provide better colour, brightness and contrast than other systems, but in a smaller, lighter package. It provides key information to the driver without them having to take their eyes away from the road.

But according to Chu, the technology’s potential has yet to be fully realised, and its real advantage is what it could be used for in future models. “What we really want to see is a fully 3D display which can provide much more information to the driver in a non-intrusive way – this is still a first generation piece of technology,” he said.

For a technology that feels somewhat futuristic, HUDs actually have a long history. The earliest HUDs were developed during the Second World War to help pilots hit their targets while manoeuvring. The modern HUD became commonplace in military aircraft in the 1960s, in commercial aircraft in the 1970s, and in 1988, the first production car with a HUD was introduced.

In aircraft, a typical HUD includes information such as airspeed, altitude, heading and a horizon line, with additional information such as distance to target and weapon status for military applications.

Most of the HUDs in passenger cars display similar information as can be seen on the dashboard – speedometer and tachometer, as well as navigation information. Some models also display night vision information.

The commercially-available Cambridge HUD projects information which is relevant to the driver onto the windscreen, in full colour and in two dimensions. But according to Chu, this type of technology is just getting started.

“There are three main types of information that we could integrate into future holographic head-up displays in the future,” he said. “The first is the type of information that’s on today’s displays, but potentially we could add other information in a non-intrusive way: for example, if the driver passes a petrol station, perhaps the price of petrol at that station could flash up in the corner – the trick is how to display the most useful information in a way that doesn’t distract the driver.

“The next level of information that could be incorporated into holographic HUDs is information about the position of pedestrians, cyclists, kerbs or other vehicles; or whether the driver is on the right track. And if we move into the next level, we start thinking about how we can use this sort of technology to help encourage good driving behaviour.”

Although it is the realm of fantasy at the moment, the sorts of things which Chu envisions for future holographic HUDs could help avoid accidents by monitoring driver behaviour. “Imagine if this technology could be used to give alerts to the driver if they were driving too fast, or getting drowsy, or were over the legal alcohol limit. You could have all of this information with an augmented reality approach – your screen is your world, really. What I want is for the driver to have an immersive experience in how they connect to the world.”

The sort of immersive experience which Chu predicts crosses over with the development of autonomous or driverless cars, another project which involves researchers from Cambridge’s Engineering department.

“The car will evolve,” said Chu. “I’m sure in 50 years’ time, everything in cars will be controlled by computers, but it’s being developed in different directions. The sorts of questions we’re interested in answering are around the idea of integrating critical and non-critical systems in a vehicle. When these systems are integrated, who ultimately makes the decision – the car or the driver? And in the case of disagreement, who wins?”

Lee Skrypchuk, Human Machine Interface Technical Specialist at Jaguar Land Rover, said: “The development of a laser holographic HUD presented a number of technical challenges but also a number of benefits including small package size, high optical efficiency, wide colour gamut and cross platform compatibility. Incorporating a laser holographic light engine was a true world first application of technology for Jaguar Land Rover and I'm delighted that the technology has worked so well in our vehicles.”

Enzymes are biological catalysts – molecules that speed up chemical reactions within living materials. Many enzymes are already well characterised and their functions fairly well understood. For example, the enzyme known as MMP8 is present in the connective tissue of most mammals, where it breaks the chemical bonds found in collagen.

In pre-clinical research published in the journal Chemistry & Biology, Dr Florian Hollfelder from the Department of Biochemistry at Cambridge and Dr Lutz Jermutus,Senior Director, Research and Development at MedImmune, led a study to map a list of human enzymes (proteases) against potential protein drug targets.

Using automation technology at MedImmune, the team then tested each of the enzymes against each target protein in turn, allowing them to identify a significant number of so-far unknown interactions.

Of particular interest was how MMP8 was able to disable a molecule known as IL-13, which is known to play an important role in several inflammatory diseases such as asthma and dermatitis. The researchers believe this may be a previously-unknown way in which the body regulates the action of IL-13, preventing these diseases in the majority of individuals. If so, it could provide an interesting target for new drugs against these common diseases.

“MMP8 is well-known to biochemists and we all thought we understood its function, but it’s clear that this – and probably many other enzymes – ‘moonlight’ and have several functions within the body,” explains Dr Hollfelder. “Because the enzyme already had a ‘name’ and a function, nobody thought to see if it had a promiscuous side.”

Designing new enzymes has proven an extremely difficult technical challenge, hence the drive to find new uses for previously ‘understood’ enzymes. By focusing on human proteases, rather than bacterial proteases – which are actually easier to source – the researchers are confident that their research will be far more applicable to drug discovery.

“Our approach is new: we ‘recycle’ known enzymes and ask whether they can do other things than the ones they are known for,” adds Dr Jermutus. “In fact, we believe we have found other enzymes that could be similarly deployed against other disease-causing proteins, and this approach, if expanded, could provide further leads for new drugs.”

Commenting on the benefits of the collaboration with industry, Dr Hollfelder adds: “Without MedImmune, our work would have stopped after seeing and characterising the interactions. The additional extension to cell and mouse models would have been inconceivable in my basic science group.”

Reference
Urbach, C et al. Combinatorial Screening Identifies Novel Promiscuous Matrix Metalloproteinase Activities that Lead to Inhibition of the Therapeutic Target IL-13. Chemistry & Biology; 19 Nov 2015

Health services in many countries increasingly rely on prescribed 'psychosocial interventions': treatments that use counselling techniques to tackle mental health issues, behavioural problems such as substance abuse, and assist parents with new or troubled children.

These highly-regarded therapeutic and educational programmes, devised by senior academics and practitioners, are sold commercially to public health services across the world on the basis that they are effective interventions for people in need of support – with the evidence to back them up.

However, the first study to investigate conflicts of interest in the published evidence for intervention treatments has revealed that the majority of academic studies which assert evidence of effectiveness list authors who profit from the distribution of these programmes, yet few declare a conflict of interest.

In fact, the new research shows that as many as two-thirds of the studies that list an author who financially benefits from sales of said treatment programmes declare no conflict of interest whatsoever.

While major steps have been taken to counter research bias in other fields such as pharmaceuticals, the new study's authors say that hugely influential psychosocial treatments suffer a distinct lack of transparency from academics that both publish research on treatment effectiveness and stand to gain significantly from any positive findings.

They write that as commercial psychosocial treatments – many of which cost hundreds, even thousands, of dollars per participant – continue to gain traction with national public health services, it is important that "systems for effective transparency are implemented" to ensure clinical commissioning bodies are aware of potential research biases. The findings are published today in the journal PLOS ONE.

"Contrary to some, I have no problem with introducing commercial programmes into a national health service if decision makers and trusts come to the conclusion that a commercially disseminated treatment is more effective than their current psychosocial offerings, but this must be based on fair and transparent evidence," said the study's lead author Professor Manuel Eisner, from Cambridge's Institute of Criminology.

"What you don't want to see is an intervention system that remains as effective, or becomes less effective, despite buying in expensive programmes, because you have a public goods service competing with research that has a commercial interest to publish overly optimistic findings," Eisner said.

"Policy makers in public health have a right to expect transparency about conflicts of interest in academic research."

Four internationally disseminated psychosocial interventions – described by Eisner as "market leaders"– were examined: the Positive Parenting Programme (or Triple P); the Nurse-Family Partnership; the parenting and social skills programme Incredible Years; the Multi-Systemic Therapy intervention for youth offenders.

The researchers inspected all articles published in academic journals between 2008 and 2014 on these interventions that were co-authored by at least one lead developer of the programme – a total of 136 studies.

Two journal editors refused consent to be included in the research, leaving 134 studies. Of all these studies, researchers found 92 of them – equalling 71% – to have absent, incomplete or partly misleading conflict of interest disclosures.

The research team contacted journal editors about the 92 published studies on the effectiveness of one of these four commercial psychosocial interventions co-authored by a primary developer of the self-same therapy, yet listed no conflict of interest, or, in the case of a few, an incomplete one.

This led to 65 of the studies being amended with an 'erratum', or correction. In 16 cases, the journal editors admitted "mishandling" a disclosure, resulting in the lack of a conflict of interest statement.

In the remaining 49 cases, the journal editors contacted the study's authors seeking clarification. In every case the authors submitted a new or revised conflict of interest. Eisner and colleagues write that the "substantial variability in disclosure rates suggests that much responsibility seems to lie with the authors".

The most common reason given by those journals that did not issue a correction was that they did not have a conflict of interest policy in place at the time of the published study's submission.

While the overall rate of adequate disclosures in clear cases of conflict of interest was less than a third, just 32%, the rates for the four programmes varied significantly. The lowest rate of disclosures was found in academic studies on the Triple P programme, at just 11%.

Triple P is a standardised system of parenting support interventions based on cognitive-behavioural therapy. Initially developed by Professor Matthew Sanders at the University of Queensland, Triple P has sold around seven million copies of its standard programme across 25 countries since it began commercial operations in 1996, with over 62,000 licensed providers – mainly trained psychologists.

In 2001, Queensland 'spun out' the licencing contract into a private company, the royalties from which are distributed between three groups of beneficiaries: Queensland University itself, Prof Sanders'Parenting and Family Support Centre (also at Queensland), and the authors of Triple P.

Despite being one of the most widely evaluated parenting programmes worldwide, the evidence for the success of Triple P is controversial, say the researchers.

Several analyses of Triple P – including those by Triple P authors with previously undeclared conflicts of interest – show positive effects. However, at least one independent systematic review cited in the new PLOS ONE study found "no convincing evidence" that the Triple P has any positive effects in the long run.

"Researchers with a conflict of interest should not be presumed to conduct less valid scholarship, and transparency doesn't necessarily improve the quality of research, but it does make a difference to how those findings are assessed," said Eisner.

In the Journal of Child and Family Studies in January 2015, Triple P creator Prof Sanders wrote that "[p]artly as a result of these types of criticisms" his research group had "undertaken a comprehensive review of our own quality assurance practices".

Added Eisner: "The development of standardised, evidence-based programmes such as Triple P is absolutely the right thing to do. If we have comparable interventions providing an evidence base then it promotes innovation and stops us running around in circles. But we need to be able to trust the findings, and that requires transparency when it comes to conflicts of interest."

The University of Cambridge and Cambridge City Council have underlined their support for diversity and equality across the city and beyond by taking the Equality Pledge.

Joining them are leading organisations from across the county including councils and emergency services.

The Equality Pledge is being made today during the national pre-launch celebration event for Lesbian, Gay, Bisexual and Trans History Month 2016 which is being hosted in Cambridge.

Setting out how organisations in the county value diversity, the Equality Pledge states:

“We believe in the dignity of all people and their right to respect and equality of opportunity. We value the strength that comes with difference and the positive contribution that diversity brings to our community. Our aspiration is for Cambridge and the wider region to be safe, welcoming and inclusive.”

Eilis Ferran, Pro-Vice-Chancellor for Institutional and International Relations at the University of Cambridge, said: “Diversity and equality play a crucial role in sustaining the University’s academic excellence. With more than 10,000 employees the University is a microcosm of Cambridgeshire’s diverse population and by taking the Equality Pledge we are recognising and celebrating and supporting that diversity.

“We hope that other organisations and individuals will join us in this important initiative.”

Cllr Lewis Herbert, Leader of Cambridge City Council: “One of Cambridge’s greatest undoubted strengths as a city is its uniquely diverse nature, attracting people from all over the world, some of whom have fled persecution and intolerance elsewhere.

“By making the Equality Pledge we are clearly stating the commitment of our city to being open and welcoming to everyone who lives here, works here or visits here.”

The partner institutions also signing up to the Equality Pledge are: Cambridge University Hospitals NHS Foundation Trust, East Cambridgeshire District Council, Police and Crime Commissioner for Cambridgeshire, Cambridgeshire Constabulary, Huntingdonshire District Council, Fenland District Council, Cambridgeshire County Council, and South Cambridgeshire District Council, and Cambridgeshire Fire and Rescue Service.

To make your own Equality Pledge visit: www.cambridge.gov.uk/equality-pledge. You can also show your support by Tweeting the special Twitter-friendly Equality Pledge: “Dignity. Respect. Equality. We value the strength that comes with difference & the positive contribution diversity brings”. The hashtag is: #EqualityPledge.

The formal launch of the Pledge takes place tonight at 6pm at Queens’ College in Cambridge (November 26) at a special showcase event marking the pre-launch celebration for Lesbian, Gay, Bisexual and Trans History Month 2016.

Image credit: Cambridge News. L-R,  Kevin Coutinho of the University's Equality and Diversity section with Eilis Ferran, Pro-Vice-Chancellor for Institutional and International Relations.

The results, published in the journal Science, are based on new radio observations tracking a star as it gets torn apart by a black hole. Such violent events yield a burst of light which is produced as the bits and pieces of the star fall into the black hole. For the first time, the researchers were able to show that this burst of light is followed by a radio signal from the matter that was able to escape the black hole by travelling away in a jetted outflow at nearly the speed of light.

The discovery of the jet was made possible by a rapid observational response after the stellar disruption (known as ASAS-SN-14li) was announced in December 2014. The radio data was taken by the by the 4 PI SKY team at Oxford, using the Arcminute Microkelvin Imager Large Array located in Cambridge.

“Previous efforts to find evidence for these jets, including my own, were late to the game,” said Sjoert van Velzen of Johns Hopkins University, the study’s lead author. Co-author Nicholas Stone added that “even after they got to the game, these earlier attempts were observing from the bleachers, while we were the first to get front row seats.”

In this branch of astronomy, the ‘front row’ means a distance of 300 million light years, while previous observations were based on events at occurring least three times as far away.

Jets are often observed in association with black holes, but their launch mechanism remains a major unsolved problem in astrophysics. Most supermassive black hole are fed a steady diet of gas, leading to jets that live for millions of years and change little on a human timescale. However, the newly discovered jet behaved very differently: the observations show that following a brief injection of energy, it produced short but spectacular radio fireworks.

The observed jet was anticipated by the so-called scale-invariant model of accretion, also known as the Matryoshka-doll theory of astrophysics. It predicts that all compact astrophysical objects (white dwarfs, neutron stars, or black holes) that accrete matter behave and look the same after a simple correction based on solely the mass of the object. In other words, the larger Matryoshka doll (a supermassive black hole) is just a scaled-up version of the smaller doll (a neutron star). Since neutron stars consistently produce radio-emitting jets when they are supplied with a large amount of gas, the theory predicts that supermassive black holes should do the same when they swallow a star.

“I always liked the elegant nature of the scale-invariant theory, but previous observations never found evidence for the new type of jet it predicted,” said van Velzen. “Our new findings suggest that this new type of jet could indeed be common and previous observations were simply not sensitive enough to detect them.”

“These jets are a unique tool for probing supermassive black holes,” said co-author Dr Morgan Fraser of Cambridge’s Institute of Astronomy. “While black holes themselves do not emit light, by observing how a star is torn apart as it falls in we can indirectly study the sleeping monster at the heart of a galaxy.”

The study hypothesises that every stellar disruption leads to a radio flare similar to the one just discovered. Ongoing surveys such as the Gaia Alerts project, led by the University of Cambridge will find many more of these rare events.

“Gaia has exceptionally sharp eyes, and is ideally suited to find events like this, which occur in the very centres of galaxies,” said co-author Dr Heather Campbell, also from Cambridge’s Institute of Astronomy. “Finding more of these rare events may further our understanding of the processes that allow black holes to launch such spectacular outflows.”

Reference:
Van Velzen, S. et. al. ‘A radio jet from the optical and X-ray bright stellar tidal disruption flare ASASSN-14li.’ Science (2015). DOI: 10.1126/science.aad1182

Adapted from a Johns Hopkins press release. 

The groundbreaking for a £32 million expansion of Cambridge Judge Business School capped a 25^th anniversary year that also included a focus on women in business, creation of a new Entrepreneurship Centre and a gala reception at the House of Lords.

“This is a very special occasion,” said Professor Sir Leszek Borysiewicz, Vice-Chancellor of the University of Cambridge, who participated in the 26 November groundbreaking ceremony. “Twenty-five years ago it was a dream that we would set up a business school here that is distinctive and different.”

The new 4,790-square-metre Simon Sainsbury Centre, which will include new lecture theatres, seminar rooms and dining facilities, will help further “the integration of the business school into everything the University does,” he said, adding that it was important that the business school is located at the heart of the University community in the centre of Cambridge.

The new building is supported in part by a generous donation from the Monument Trust, whose founder Simon Sainsbury was one of the business school’s original benefactors a quarter century ago. The new building, designed by London architects Stanton Williams, will sit directly behind the former Addenbrooke’s Hospital building that now houses Cambridge Judge.

The role of women in business has formed a central part of the 25^th anniversary year at Cambridge Judge. A new Women’s Leadership Initiative was launched at the School to serve as a platform to enable women’s empowerment and leadership in the business world globally, and held its inaugural conference in June. A study on “The Rise of Women in Society: enablers and inhibitors” led by Sucheta Nadkarni, Sinyi Professor of Chinese Management at Cambridge Judge, was unveiled at a London conference and attracted worldwide attention; it found that increasing the economic power of women throughout society, rather than quotas, is the key factor in women reaching and staying on corporate boards.

In addition, the Executive Education division of Cambridge Judge teamed up in with LexisNexis to publish a new magazine, FLUX, which examines women in the legal profession, while Cambridge Judge also agreed to sponsor a Woman Entrepreneur of the Year award in Business Weekly publication’s annual awards.

The new Entrepreneurship Centre, which in July welcomed to Cambridge its patron, HRH The Duke of York, KG, creates a new centre that reflects the full journey of entrepreneurship – from idea creation to attracting start-up funding to growth. It brings together several of the business school’s initiatives including the Centre for Entrepreneurial Learning (CfEL) and Accelerate Cambridge, while serving as a focal point for the School’s interaction with the wider Cambridge Cluster of research and enterprise.

“The Centre is not just an academic exercise, but matters to Cambridge and indeed to the UK,” Cambridge Judge Director Christoph Loch told the Duke of York and other guests – adding that the new Centre will help individuals prepare for entrepreneurial activity, develop their management skills and address the “scale-up problem” that impairs many young companies’ ability to grow.

Complementing the new Entrepreneurship Centre is a recently opened Centre for Social Innovation, which is overseeing the launch in 2016 of a new part-time two-year Masters in Social Innovation programme.

The 25^th anniversary reception in September, attended by 250 people at the House of Lords, was hosted by Lord Bilimoria of Chelsea, CBE, DL, a member of the Cambridge Judge Advisory Board. A nine-minute video shown at the event recounted the School’s origins and themes – including student diversity and how business can play a positive role in society.

“Cambridge didn’t have a business school at all, but within the Engineering Department students could take management studies,” Professor Stephen Watson, inaugural Director of Cambridge Judge (1990-1994), recalls in the video. “We thought there ought to be more than this, we thought in fact there out to be a full-scale business school in Cambridge.”

So that’s what happened. From a first class of just 19 MBA and 19 MPhil students, Cambridge Judge this year has 157 MBA students, 63 Executive MBA students, 64 Master of Finance students, 32 PhD students, 126 MPhil students and 41 undergraduates attending classes.

The expansion of programmes and the student body means that the historic Addenbrooke’s Hospital and adjacent buildings are too small to accommodate all the school’s activities. So when completed in 2017 the new building will provide world-class teaching and conferencing facilities for the School’s next quarter century and beyond.

Now on display at the Fitzwilliam Museum, The Kiss of Judas, is one of the rarest artworks of its type. At the time of the Reformation and during the English Civil War, church paintings were destroyed in their thousands. Few survive across the UK and of those that remain, many have been defaced. It is believed that up to 97% of English religious art was destroyed during and after the Reformation.

The brightly-painted wooden panel, with details picked out in silver and gold leaf, dates from c.1460, is all the more astonishing as it depicts the moment of Christ’s betrayal, by Judas Iscariot. Devout Catholic parishioners often scratched and gouged at the hated figure of Judas, so the painting would have been at risk from Catholic and Protestant congregations alike during the intervening centuries.

The remarkable discovery of the painting’s double life was revealed when it was purchased by the Fitzwilliam Museum in 2012 from the Church of St Mary, Grafton Regis, Northamptonshire. The church did not have the funds to conserve the work and maintain it in appropriate environmental conditions. 

When the panel arrived at the Fitzwilliam’s Hamilton Kerr Institute for conservation, it had a considerable layer of surface dirt, bat faeces and heavily discoloured varnish which made it difficult to see the image. 

But, it was a discovery on the back of the boards that revealed the remarkable story of how the painting survived.

The reverse was covered with a more modern backing board of plywood. When conservator Dr Lucy Wrapson removed this, she found the back of the planks making up the painting had, under close inspection, faint traces of writing. 16th century lettering was revealed using infra-red photography, proving the painting had been recycled at the time of the Reformation, the offending image turned around and the back converted into a painted board. It is thought that it may have listed the Ten Commandments, typical of a Protestant church furnishing.

 

Dr Wrapson said: “We cannot know for sure why the painting was re-used in this fashion, perhaps it was simple economy, reversed so it could still fit the space for which it was intended.  Or perhaps it could have been deliberately saved.  The painting is fascinating, and conservation and cleaning has revealed the vibrant original medieval colours.”

The painting was dated by dendrochronologist Ian Tyers. The panel is made up of boards imported to England from the eastern Baltic, Ian looked at the growth rings and identified the tree was felled after 1423 and estimated a usage date of c.1437-1469. Further non-invasive X-ray analysis and assessment using infra-red and ultraviolet light identified details, pigments and possible areas of fragility. Cleaning, protection of the wood from further insect damage, and a new layer of modern varnish have preserved the object for generations to come.

The painting is on display in the Rothschild Gallery of medieval works in the Fitzwilliam Museum. Funds from the sale will now help fix the roof of St Mary’s. Entry to the museum is free.

About one in nine people globally still suffer from hunger, with the majority living in Africa and Asia. The world’s forests have great potential to improve their nutrition and ensure their livelihoods. In fact, forests could be essential to global food security, particularly when considering the importance of diverse, nutritionally-balanced diets.

Forests are key to protecting biodiversity, and for mitigating the effects of climate change. This is well known. However their contribution to alleviating hunger and improving nutrition has been somewhat neglected. A recent study by the Global Forest Expert Panel on Forests and Food Security, which I chaired, shows how forests and trees can complement agricultural production and give an economic boost to some of the world’s most vulnerable regions.

Four ways forests benefit food security

• Tree foods are often rich in vitamins, proteins, and other nutrients and are associated with more diverse diets. For example, the iron content of dried seeds of the African locust bean and raw cashew nut are comparable with, or even higher than that of chicken meat. Trees in home gardens, widespread in Africa and Asia, increase fruit and vegetable consumption.

• Wild meat, fish, and insects are also important forest food sources. Insects are an especially cheap, abundant source of protein and fat. Caterpillars are great for vitamins and minerals. Particularly in South-East Asia, many forests and agroforests (tree-based farms) are managed by local communities specifically to enhance edible insect supply, such as the management of sago palms in Papua New Guinea and eastern Indonesia to support grub production.

• Forests are also essential for firewood and charcoal. In developing countries, 2.4 billion people still use wood-fuel for cooking and heating. In India and Nepal, even better-off rural households depend on it. The volatile and often high prices for other energy sources suggest this situation is unlikely to change for some time. Access to cooking fuel provides people with more flexibility in what they can eat, including more nutritious foods that require more energy to cook.

• Trees offer a multitude of ecological services. For instance, they support bees and other pollinators, which are essential for crop production including on farmland. They also provide animal fodder that enables communities to produce meat and milk, and protect streams and watersheds as habitat for fish.

Close to one out of six people directly depend on forests for their food and income, and it is important to recognise the rights of local people to these livelihood options. In the Sahel, for example, trees can contribute as much as 80% to household incomes, especially through shea nut production.

Novel initiatives are attempting to develop new tree commodities to supply the poor with sustainable incomes. For example, poor producers in Tanzania are engaged in a global effort to produce the seeds of the Allanblackia crop, which yield an edible oil. A private–public partnership known as Novella Africa is developing a sustainable Allanblackia oil business that could be worth hundreds of millions of dollars annually for local farmers.

From forest to farm

Although forests are not a panacea for global hunger, they play a vital role in complementing crops produced on farms. This is especially important when the staple food supply is impaired by droughts, volatile prices, armed conflicts, or other crises.

While large-scale crop production remains important, it is highly vulnerable to extreme weather events, which may occur more frequently under climate change. Tree-based farming can adapt far better to such calamities. During periods of food shortage triggered by such events, forest foods can provide a vital safety net, especially for the poorest households.

This forest-farm link also means that the loss and degradation of forests exacerbate the problem of food insecurity. Losing forests jeopardises “ecological services” such as a clean water supply, crucial for crop and livestock production. Managing landscapes on a multi-functional basis that combines food production, the maintenance of ecosystem services and other land use services should be at the forefront of efforts to achieve global food security.

In the lead up to the UN’s finalisation of the Sustainable Development Goals later this year, the contribution of forests and tree-based systems to the “Zero Hunger Challenge” needs to be emphasised. They can be managed to provide better and more nutritionally-balanced diets, greater control over food inputs – particularly during lean seasons and periods of vulnerability (especially for marginalised groups) – and deliver ecosystem services for crop production. It will be a critical element of the responses to global hunger.

Bhaskar Vira, Reader in Political Economy at the Department of Geography and Fellow of Fitzwilliam College; Director, University of Cambridge Conservation Research Institute, University of Cambridge

This article was originally published on The Conversation. Read the original article.

The opinions expressed in this article are those of the individual author(s) and do not represent the views of the University of Cambridge.