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Cambridge United News Feed - 12 hours 19 min ago

Ticket News

The U's return to the Abbey for the final time this season against Morecambe on Saturday in Sky Bet League Two – Tickets available now!

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MATCH REPORT | FOREST GREEN ROVERS 2 CAMBRIDGE UNITED 1

Cambridge United News Feed - Mon, 04/22/2019 - 17:35

Match Reports

Results elsewhere in Sky Bet League Two confirmed the U’s position in the Football League with two games of the season remaining, despite a frustrating 2-1 defeat at Forest Green Rovers on Easter Monday.

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MATCH REPORT | CAMBRIDGE UNITED 0 SWINDON TOWN 0

Cambridge United News Feed - Fri, 04/19/2019 - 17:30

Match Reports

Cambridge United produced a much improved and resolute home performance picking up a point in a goalless draw against Swindon Town, which moved United onto the brink of League Two safety.

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2018/19 PLAYER OF THE SEASON VOTE OPEN

Cambridge United News Feed - Fri, 04/19/2019 - 10:40

Club News

The Amber Army can now vote for their 2018/19 Cambridge United Player of the Season, with the presentation set to take place following the closing home fixture against Morecambe at the Abbey Stadium on Saturday 27th April.

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CAMBRIDGE UNITED SUPPORTERS' PANEL - ELECTION RESULT CONFIRMED

Cambridge United News Feed - Fri, 04/19/2019 - 10:17

Club News

Cambridge United FC is pleased to announce the result of the recent ballot to elect the fans that will make up first Cambridge United Supporters’ Panel - in order of votes received:

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PROGRAMME PREVIEW | SWINDON TOWN – JEVANI BROWN

Cambridge United News Feed - Thu, 04/18/2019 - 17:02

Club News

Jevani Brown has urged the U’s to make the clash with Swindon Town the game where the U’s cross the line and secure their League Two safety in tomorrow’s match day programme – Read a preview here!

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Discovery of genetic variants that protect against obesity and type 2 diabetes could lead to new weight loss medicines

Cambridge University NewsFeed - Thu, 04/18/2019 - 16:00

Scientists have known for several years that genes can influence a person’s weight. One of the genes that is known to play a key role in regulating weight is MC4R, which codes for the melanocortin 4 receptor. This receptor acts like a switch in the brain to suppress appetite. People who have genetic variants that disrupt this receptor gain weight easily.

Now, in a study published today in the journal Cell, researchers have shown that other genetic variants in the MC4R gene that increase the activity of this brain receptor can protect people from becoming overweight, a finding that could lead to the development of new medicines that ‘copy’ the protective effect of these genetic variants to achieve or maintain weight-loss.

A team led by Professors Sadaf Farooqi and Nick Wareham and Dr Claudia Langenberg at the Wellcome Trust-MRC Institute of Metabolic Science in Cambridge looked at the MC4R gene in half a million volunteers from the UK population who have taken part in the UK Biobank study, finding 61 distinct naturally-occurring genetic variants. While some of these genetic variants predisposed people to become obese, other variants provided protection against obesity and some of its major complications, such as type 2 diabetes and heart disease.

To investigate the reasons for this mystery, Professor Farooqi’s team, who previously showed that MC4R works in the brain as a ‘switch’ to tell us to stop eating after a meal, studied the function of these genetic variants in a number of laboratory experiments. They found that MC4R gene variants linked to higher obesity risk stopped the gene from working, whereas variants that offered protection against obesity kept the gene ‘switched on’.

Around six per cent of study participants carried genetic variants that caused the receptor to remain ‘switched on’. People with these variants would eat less, which could explain their lower weight. People with two copies of these particular variants (1 in over 1,000 people) were on average 2.5 kg lighter than people without the variants and had a 50% lower risk of type 2 diabetes and heart disease.

“This study drives home the fact that genetics plays a major role in why some people are obese – and that some people are fortunate enough to have genes that protect them from obesity,” says Professor Farooqi of the University of Cambridge Metabolic Research Laboratories.

The discovery adds to recent work by the team which showed that some slim people have a genetic advantage when it comes to maintaining their weight.

“It doesn’t mean that we can’t influence our weight by watching what we eat, but it does mean the odds are stacked against some people and in favour of others,” added Professor Farooqi.

When the researchers looked in detail at the genetic variants in laboratory experiments, they found that MC4R can send signals through a pathway – known as the beta-arrestin pathway – that had not previously been linked to weight regulation. Genetic variants that sent signals preferentially through this pathway were the ones driving the association with protection against obesity and its complications and, importantly, were also associated with lower blood pressure. Designing drugs that mimic the effect of the protective variants in MC4R could provide new, safer weight loss therapies.

“A powerful emerging concept is that genetic variants that protect against disease can be used as models for the development of medicines that are more effective and safer,” said Dr Luca Lotta, Senior Clinical Investigator at the Medical Research Council Epidemiology Unit and joint lead author of the study. “Our findings may pave the way for a new generation of weight loss therapies that activate MC4R preferentially via the beta-arrestin pathway.”

“Our work would not have been possible without the unique blend of expertise in large-scale genetic epidemiology analysis and laboratory experiments at the Institute of Metabolic Science,” says Professor Wareham, Director of the MRC Epidemiology Unit and Co-Director of the Institute.

“Genetic studies of thousands of people and a functional understanding of the mechanisms behind protective genetic variants can really help us inform the development of a new generation of medicines for common diseases like obesity and diabetes that affect millions of people globally.”

The work was funded by the MRC and Wellcome, with support from the NIHR Cambridge Biomedical Research Centre.

Reference
Lotta, LA, Mokrosiński, J et al. Human gain-of-function MC4R variants show signaling bias and protect against obesity. Cell; 18 April 2019; DOI: 10.1016/j.cell.2019.03.044

Around four million people in the UK carry genetic variants that protect them from obesity, type 2 diabetes and heart disease, suggests new research from the University of Cambridge. The team say the discovery could lead to the development of new drugs that help people lose weight.

This study drives home the fact that genetics plays a major role in why some people are obese – and that some people are fortunate enough to have genes that protect them from obesitySadaf FarooqiSiora PhotographyTape measure


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INTRODUCING THE 12TH FAN…COLIN PROCTOR

Cambridge United News Feed - Thu, 04/18/2019 - 12:44

Club News

Cambridge United are delighted to introduce tomorrow’s 12th Fan and therefore leading the U’s out at the Abbey Stadium against Swindon Town, former FED and now Honorary Director Colin Proctor.

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SEASON TICKET AND MATCH TICKET PRICE FREEZE AS EARLY BIRD WINDOW OPENS FOR 2019/2020

Cambridge United News Feed - Thu, 04/18/2019 - 10:58

Ticket News

2019/2020 SEASON TICKETS ON SALE NOW

Cambridge United can today confirm season ticket and match ticket prices have been frozen for the 2019/2020 season, with the early bird window now open for supporters to secure their place at the Abbey Stadium.

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Blood pressure drug shows promise for treating Parkinson’s and dementia in animal studies

Cambridge University NewsFeed - Thu, 04/18/2019 - 10:00

A common feature of these diseases – collectively known as neurodegenerative diseases – is the build-up of misfolded proteins. These proteins, such as huntingtin in Huntington’s disease and tau in some dementias, form ‘aggregates’ that can cause irreversible damage to nerve cells in the brain.

In healthy individuals, the body uses a mechanism to prevent the build-up of such toxic materials. This mechanism is known as autophagy, or ‘self-eating’, and involves ‘Pac-Man’-like cells eating and breaking down the materials. However, in neurodegenerative diseases this mechanism is impaired and unable to clear the proteins building up in the brain.

As the global population ages, an increasing number of people are being diagnosed with neurodegenerative diseases, making the search for effective drugs ever more urgent. However, there are currently no drugs that can induce autophagy effectively in patients.

In addition to searching for new drugs, scientists often look to re-purpose existing drugs. These have the advantage that they have already been shown to be safe for use in humans. If they can be shown to be effective against the target diseases, then the journey to clinical use is much faster.

In a study published today in the journal Nature Communications, scientists at the UK Dementia Research Institute and the Cambridge Institute for Medical Research at the University of Cambridge have shown in mice that felodipine, a hypertension drug, may be a candidate for re-purposing.

Epidemiological studies have already hinted at a possible link between the drug and reduced risk of Parkinson’s disease, but now the researchers have shown that it may be able to induce autophagy in several neurodegenerative conditions.

A team led by Professor David Rubinsztein used mice that had been genetically modified to express mutations that cause Huntington’s disease or a form of Parkinson’s disease, and zebrafish that model a form of dementia.

Mice are a useful model for studying human disease as their short life span and fast reproductive rate make it possible to investigate biological processes in many areas. Their biology and physiology have a number of important characteristics in common with those of humans, including similar nervous systems.

Felodipine was effective at reducing the build-up of aggregates in the mice with the Huntington’s and Parkinson’s disease mutations and in the zebrafish dementia model. The treated animals also showed fewer signs of the diseases.

Studies in mice often use doses that are much higher than those known to be safe to use in humans. Professor Rubinsztein and colleagues showed in the Parkinson’s mice that it is possible to show beneficial effects even at concentrations similar to those tolerated by humans. They did so by controlling the concentrations using a small pump under the mouse’s skin.

“This is the first time that we’re aware of that a study has shown that an approved drug can slow the build-up of harmful proteins in the brains of mice using doses aiming to mimic the concentrations of the drug seen in humans,” says Professor Rubinsztein. “As a result, the drug was able to slow down progression of these potentially devastating conditions and so we believe it should be trialled in patients.”

“This is only the first stage, though. The drug will need to be tested in patients to see if it has the same effects in humans as it does in mice. We need to be cautious, but I would like to say we can be cautiously optimistic.”

The study was funded by Wellcome, the Medical Research Council, Alzheimer’s Research UK, the Alzheimer’s Society, Rosetrees Trust, The Tau Consortium, an anonymous donation to the Cambridge Centre for Parkinson-Plus, Open Targets,  the Guangdong Province Science and Technology Program, with additional support from the National Institute for Health Research Cambridge Biomedical Research Centre.

Reference
Siddiqi, FH et al. Felodipine induces autophagy in mouse brains with pharmacokinetics amenable to repurposing. Nature Communications; 18 April 2019; DOI: 10.1038/s41467-019-09494-2

A prescription drug to treat high blood pressure has shown promise against conditions such as Parkinson’s, Huntington’s and forms of dementia in studies carried out in mice and zebrafish at the University of Cambridge.

The drug will need to be tested in patients to see if it has the same effects in humans as it does in mice. We need to be cautious, but I would like to say we can be cautiously optimisticDavid RubinszteinUnderstanding Animal ResearchWhite mouse in purple gloved handsResearcher profile: Dr Farah Siddiqi

Fifteen years ago, when Farah Siddiqi was studying for a PhD in genetics, she had an encounter that was to change the direction of her career.

“During my PhD, I had the opportunity to help as a part-time research assistant for a few hours during the weekend with a professor of economics who suffered from Parkinson’s disease,” she says.

“I saw first-hand the pain and helplessness of someone suffering from a devastating neurodegenerative disease and I began to ponder how I could help reduce the suffering of others affected by these conditions.”

Farah is now part of Professor David Rubinsztein’s research group at the Cambridge Institute for Medical Research where her work focuses on neurodegenerative disorders, such as Huntington’s disease and Parkinson’s disease. She uses mice to model what is going wrong in these conditions, particularly in relation to autophagy, the body’s self-defence mechanism for disposing of unwanted matter at a cellular level. 

Their research group is very diverse, with expertise from various fields, such as cell biologists and researchers who carry out in vivo work in zebrafish and mouse research.

“Cambridge is a great place to do research and our institute in particular is a great source of inspiration and knowledge. David is a great supervisor and a big support. The intellectual and practical contribution of his team of scientists made this study possible.”  

Most of all for Farah, it is the sense that her research could make a difference to the lives of people living with neurodegenerative diseases that inspires her.

“My research gives me a feeling of contentment, especially when I began to observe the beneficial effects of the drug, felodipine, on mice,” she says. “It might be a little optimistic, but we really hope the effect we’ve seen in our mice can be observed in human patients. Only time will tell. We always do our best.”


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Green material for refrigeration identified

Cambridge University NewsFeed - Thu, 04/18/2019 - 10:00

When put under pressure, plastic crystals of neopentylglycol yield huge cooling effects – enough that they are competitive with conventional coolants. In addition, the material is inexpensive, widely available and functions at close to room temperature. Details are published in the journal Nature Communications.

The gases currently used in the vast majority of refrigerators and air conditioners —hydrofluorocarbons and hydrocarbons (HFCs and HCs) — are toxic and flammable. When they leak into the air, they also contribute to global warming.

“Refrigerators and air conditioners based on HFCs and HCs are also relatively inefficient,” said Dr Xavier Moya, from the University of Cambridge, who led the research with Professor Josep Lluís Tamarit, from the Universitat Politècnica de Catalunya. “That’s important because refrigeration and air conditioning currently devour a fifth of the energy produced worldwide, and demand for cooling is only going up.”

To solve these problems, materials scientists around the world have sought alternative solid refrigerants. Moya, a Royal Society Research Fellow in Cambridge’s Department of Materials Science and Metallurgy, is one of the leaders in this field.

In their newly-published research, Moya and collaborators from the Universitat Politècnica de Catalunya and the Universitat de Barcelona describe the enormous thermal changes under pressure achieved with plastic crystals.

Conventional cooling technologies rely on the thermal changes that occur when a compressed fluid expands. Most cooling devices work by compressing and expanding fluids such as HFCs and HCs. As the fluid expands, it decreases in temperature, cooling its surroundings.

With solids, cooling is achieved by changing the material’s microscopic structure. This change can be achieved by applying a magnetic field, an electric field or through mechanic force. For decades, these caloric effects have fallen behind the thermal changes available in fluids, but the discovery of colossal barocaloric effects in a plastic crystal of neopentylglycol (NPG) and other related organic compounds has levelled the playfield.

Due to the nature of their chemical bonds, organic materials are easier to compress, and NPG is widely used in the synthesis of paints, polyesters, plasticisers and lubricants. It’s not only widely available, but also is inexpensive.

NPG’s molecules, composed of carbon, hydrogen and oxygen, are nearly spherical and interact with each other only weakly. These loose bonds in its microscopic structure permit the molecules to rotate relatively freely.

The word “plastic” in “plastic crystals” refers not to its chemical composition but rather to its malleability. Plastic crystals lie at the boundary between solids and liquids.

Compressing NPG yields unprecedentedly large thermal changes due to molecular reconfiguration. The temperature change achieved is comparable with those exploited commercially in HFCs and HCs.

The discovery of colossal barocaloric effects in a plastic crystal should bring barocaloric materials to the forefront of research and development to achieve safe environmentally friendly cooling without compromising performance.

Moya is now working with Cambridge Enterprise, the commercialisation arm of the University of Cambridge, to bring this technology to market.

Reference:
P. Lloveras et al. ‘Colossal barocaloric effects near room temperature in plastic crystals of neopentylglycol.’ Nature Communications (2019). DOI: 10.1038/s41467-019-09730-9

Researchers from the UK and Spain have identified an eco-friendly solid that could replace the inefficient and polluting gases used in most refrigerators and air conditioners.

Refrigeration and air conditioning currently devour a fifth of the energy produced worldwide, and demand for cooling is only going up.Xavier MoyaJan TikAir


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Cambridge United and Cambridgeshire County Council partner to support young people’s mental health

Cambridge United News Feed - Wed, 04/17/2019 - 13:36

Community

Mental Health Drop-in Sessions

Cambridge United and Cambridgeshire County Council are working together to provide local young people and their families the opportunity to speak about their mental health at four drop-in sessions throughout the year.

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Police officers learn new methods on University course

Cambridge University NewsFeed - Wed, 04/17/2019 - 10:33

They’re the first tranche of police officers to take part in the University's Senior Leader Master's Degree Apprenticeship Degree course in Applied Criminology and Police Management. Over the next two years they’ll study latest innovations and discoveries in evidence based policing and exchange ideas about how to improve policing in their own agencies.

Noel McHugh is a Detective Chief Inspector with the Metropolitan Police:

“It’s been like doing a marathon mentally. It’s been exhausting, but fascinating because of what we’ve learned. It’s been exciting too because you see how you can apply things to policing and what we can do, especially around knife crime. There are so many ideas going around about what we can do in the future.”

The course is funded through the government’s Apprenticeship Levy, which, in an era of tight police budgets, has been a godsend. Employers who spend more than £3 million a year on salaries, pay half of one per cent of their pay bill into the Levy and this is used to fund extra training needs. The officers will assemble in Cambridge for 2 weeks, three times a year. They will write a 3000 word essay and a major critique of a piece of research before they set to work on their dissertations.

Alenkora Bediako, is a Detective Inspector with the Metropolitan Police and has been tackling organised crime for 13 years:

“What I like about what I’m learning here is that it’s directly applicable to policing. In policing, we definitely focus on learning by experience and that’s what we value the most but experience is not necessarily the best way of deciding how to do things and that’s what I’ve learned here. Also what I like is that everyone here is passionate about problems and issues and the real stories behind what we’re doing, so there’s a real meaning to that. We’re not just coming to get a Cambridge degree, we’re actually coming to try to make things better.”

Evidence based policing is the practice of applying research to decision making in policing. It’s recently been used in research where knife attack data has been analysed to predict where fatal knife attacks could occur in the future.

Phaedra Binns, is a Manager in the Counter-Terrorism Unit at Thames Valley Police:

“For me personally, you come away and you look at something like the knife crime predictive probability of an incident occurring. That’s something that, for me, that is absolutely fascinating and something that we can take away and potentially replicate. So now I’m personally motivated to go away and research that and see what’s being done, what’s effective, what we’re currently doing in the force and how we might do it better.”

Professor Sherman taking a class 

Professor Lawrence Sherman, Chair of the Police Executive Programme, says:

“I have urged the student apprentices to view the apprenticeship not only as a means of transforming their own capability to protect the public, but also as an asset for the transformation of their entire police agencies.”    

The student apprentices are overwhelmingly from state schools come from all over England. and only a handful took A levels. After the first two weeks, they’ve already been won over by the  benefits higher education can offer for policing.

DCI Noel McHugh again:

“It’s really difficult, but my advice to the young people I work with out there, on the estates and that, is that there’s no reason why they can’t come to Cambridge. They should be aiming to get here because education really is empowering. If I can get through, then there’s hope for them”

For more information on the course go to: https://www.crim.cam.ac.uk/Courses/m-st-courses/MStPolice or https://www.ice.cam.ac.uk/course/mst-applied-criminology-and-police-mana...

 

 

 

 

Some of the officers in the room are involved in counter-terrorism initiatives. Others tackle organised crime, or prevention of street violence, or safeguarding domestic abuse victims. All have risen through the ranks despite a good proportion of them having no prior experience of university.  And now they’re sitting in a lecture theatre at the University of Cambridge embarking on a new apprenticeship degree course. 

We're not just coming to get a Cambridge degree, we're actually coming to try to make things betterAlenkora BediakoUniversity of Cambridge/Paul SeagroveGroup photo of the University of Cambridge's first apprentices


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The Royal Society announces election of new Fellows 2019

Cambridge University NewsFeed - Wed, 04/17/2019 - 10:20
In total, fifty eminent scientists from the United Kingdom and the Commonwealth have been honoured, joining illustrious names such as Isaac Newton, Charles Darwin and Albert Einstein. Ten new Foreign Members have also been named.     The Cambridge academics are:   Caucher Birkar  Professor of Mathematics in the Department of Pure Mathematics and Mathematical Statistics   Peter Haynes Professor of Applied Mathematics, Department of Applied Mathematics and Theoretical Physics    Richard Jozsa Leigh Trapnell Professor of Quantum Physics, Department of Applied Mathematics and Theoretical Physics   Venki Ramakrishnan, President of the Royal Society, says:  “Over the course of the Royal Society’s vast history, it is our Fellowship that has remained a constant thread and the substance from which our purpose has been realised: to use science for the benefit of humanity.    “This year’s newly elected Fellows and Foreign Members of the Royal Society embody this, being drawn from diverse fields of enquiry—epidemiology, geometry, climatology—at once disparate, but also aligned in their pursuit and contributions of knowledge about the world in which we live, and it is with great honour that I welcome them as Fellows of the Royal Society.”    New Fellows are formally admitted to the Society at the Admissions Day ceremony in July, when they sign the Charter Book and the Obligation of the Fellows of the Royal Society.    View the full list of new Fellows and Foreign Members.

Three Cambridge academics have been made Fellows of the Royal Society in recognition of their outstanding contributions to science.

It is with great honour that I welcome them as Fellows of the Royal SocietyVenki Ramakrishnan, President of the Royal SocietyCourtesy of The Royal SocietyThe Royal Society, London.


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Additional routine ultrasounds benefit mothers and babies, and could be cost saving, study finds

Cambridge University NewsFeed - Wed, 04/17/2019 - 08:52

These are some of the conclusions of the Pregnancy Outcome Prediction study published this week in PLOS Medicine led by researchers at the University of Cambridge.

Undiagnosed breech presentation — when a baby’s buttocks or feet emerge first at birth — increases the risk of perinatal morbidity and mortality. In current practice, fetal presentation is assessed by palpation of the maternal abdomen, but the sensitivity of this approach varies by practitioner. By routinely using ultrasound screening, undiagnosed breech presentation in labour could be avoided, lowering the risk of morbidity and mortality for both mother and baby.

In the new study, researchers performed research screening ultrasounds at 36 weeks’ gestation in 3879 women having first pregnancies in England. A total of 179 women (4.6%) were diagnosed with breech presentation by the research scan. However, in over half of these cases (55%) there was no prior suspicion that the baby was presenting in the breech position.

Making the diagnosis at 36 weeks allowed women to opt for an attempt at turning the baby, called external cephalic version. For the women who declined this procedure, or where it was unsuccessful, a planned caesarean section was arranged. None of the women opted to attempt a vaginal breech birth, which is known to be associated with an increased risk of complications, particularly in first pregnancies.

Across the UK, the analysis estimated that routine scanning could prevent around 15,000 undiagnosed breech presentations, more than 4,000 emergency caesarean sections and 7 to 8 baby deaths per year. If a scan could be done for less than £12.90 then it could be cost-saving to the NHS. This could be possible once midwives are instructed how to perform the simple technique, using inexpensive portable equipment.

Professor Gordon Smith from the Department of Obstetrics and Gynaecology at the University of Cambridge, who led the study, said: “We believe the study highlights an opportunity to identify women at increased risk of a complicated birth. It seems likely that screening for breech presentation near term could be introduced in a cost-effective manner and this should be considered by the NHS and other health systems.”

The research was funded by the National Institute for National Institute for Health Research.

Reference
Wastlund, D et al. Screening for breech presentation using universal late-pregnancy ultrasonography: A prospective cohort study and cost effectiveness analysis. PLOS Medicine; 16 April 2019; DOI: 10.1371/journal.pmed.1002778

Adapted from a press release from PLOS

Offering universal late pregnancy ultrasounds at 36 weeks’ gestation eliminates undiagnosed breech presentation of babies, lowers the rate of emergency caesarean sections, and improves the health of mothers and babies. 

It seems likely that screening for breech presentation near term could be introduced in a cost-effective manner and this should be considered by the NHS and other health systemsGordon SmithFotorechPregnant woman


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HOME TICKETS | SWINDON TOWN

Cambridge United News Feed - Tue, 04/16/2019 - 10:19

Ticket News

Cambridge United are back at the Abbey Stadium on Good Friday as they look to seal the deal against Swindon Town in Sky Bet League Two – Tickets on sale now!

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‘Fingerprint database’ could help scientists to identify new cancer culprits

Cambridge University NewsFeed - Tue, 04/16/2019 - 00:19

Our DNA, the human genome, comprises of a string of molecules known as nucleotides. These are represented by the letters A, C, G and T. Sometimes, changes occur in the ‘spelling’ of our DNA – an A becomes a G, for example. These changes, known as mutations, can be caused by a number of factors, some environmental, such as exposure to tobacco smoke or to ultraviolet light.

As cells divide and multiply, they make copies of their DNA, so any spelling mistakes will be reproduced. Over time, the number of errors accumulates leading to uncontrolled cell growth – the development of tumours.

Previously, scientists have had only a limited number of tools for working out the cause of an individual’s tumour. As it is now possible to study the entire human genome very rapidly, scientists have been able to find all the mutations in a patient’s cancer, and see patterns – or ‘mutational signatures’ – in these tumours.

Now, in a study published in the journal Cell, a team of researchers from the University of Cambridge and King’s College London have developed a comprehensive catalogue of the mutational signatures caused by 41 environmental agents linked to cancer. In future they hope to expand it further, using similar experimental techniques, to produce an encyclopaedia of mutation patterns caused by environmental agents.

“Mutational signatures are the fingerprints that carcinogens leave behind on our DNA, and just like fingerprints, each one is unique,” explains Dr Serena Nik-Zainal from the Department of Medical Genetics and MRC Cancer Unit at the University of Cambridge, who led the Cambridge Team. “They allow us to treat tumours as a crime scene and, like forensic scientists, allow us to identify the culprit – and their accomplices – responsible for the tumour.”

The researchers exposed induced pluripotent stem cells – skin cells that have been reprogrammed to return to their original, ‘master’ state – to 79 known or suspected environmental carcinogens. The team then used whole genome sequencing to look at the patterns of changes caused by the agents and found that 41 of the suspects left a characteristic fingerprint on the stem cells’ DNA.

“We’ve used this technique to create the most comprehensive catalogue to date of the patterns of DNA damage produced by environmental agents across the whole human genome,” explains Professor David Phillips, who led the King’s College London team. “It should allow us to examine a patient’s tumour and identify some of the carcinogens they have been exposed to that may have caused the cancer.”

Some of the environmental agents studied are known carcinogens, such as polycyclic hydrocarbons and sunlight. For the first time, the researchers also studied some of the individual chemicals found in tobacco smoke and identified which ones cause signatures similar to those found in smokers’ lung cancer.

They also identified the fingerprints left behind by common chemotherapy drugs, some dietary chemicals and some present in diesel exhaust fumes. This study shows how human DNA is vulnerable to many agents in our surroundings.

Dr Nik-Zainal illustrates potential uses of the catalogue by referring to the case of Balkan endemic nephropathy (BEN), which is linked to dietary exposure to a plant chemical called aristolochic acid. The mutational signature of this chemical was verified in this study to be virtually identical to the signature found in the tumours of BEN patients. So, although this connection was first made prior to the current study, Dr Nik-Zainal says it is an example of how one might use their catalogue in future.

“Our reference library will allow doctors in future to identify those culprits responsible for causing cancer,” adds Dr Nik-Zainal. “Such information could be invaluable in helping inform measures to reduce people’s exposure to potentially dangerous carcinogens.”

The research was funded by a Wellcome Strategic Award, with additional support from Cancer Research UK and the Medical Research Council.

Reference
Kucab, JE & Zou, X et al. A compendium of mutational signatures of environmental agents. Cell; 2 May 2019; DOI: 10.1016/j.cell.2019.03.001

Scientists in Cambridge and London have developed a catalogue of DNA mutation ‘fingerprints’ that could help doctors pinpoint the environmental culprit responsible for a patient’s tumour – including showing some of the fingerprints left in lung tumours by specific chemicals found in tobacco smoke.

Mutational signatures ... allow us to treat tumours as a crime scene and, like forensic scientists, allow us to identify the culprit – and their accomplices – responsible for the tumourSerena Nik-ZainalgeraltCigarettes


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