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 First Published: September 24: 2015
The Humanion

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 
 

 

 

 

 

 

Biochemistry Arkive Year Beta

 

 

 

 

 

 

What Does Not Die



 

In Hampshire in an autumn wood the squirrel I found that came to say hello
In New Hampshire life’s voices went rippling human joys and sorrows and
In Union Square I saw the sun painting the green leaves with photon-paints
Allwhere life is a song written and sung in many a form in many a rainbow
A rainbow it is always allwhere marking the same shape of life-expressions

It is always in units of atoms
Units of photons and of cells
DNAs RNAs and neurons
Always the same rises ee falls
Always it is the song of cells

And the Empire State Building raised a spectacle in Manhattan skyline as
The traffic lit the air in all its expressions in the evening and in Scotland I
Saw heather and hyacinth in Swansea the light and its spread the same
Light the same song written and sung in many a form in many a rainbow
And it is the same that drives us to strive to stretch to reach to risk to rise

 

It is always magnetic
Always electric and
Chemical and active
Biochemical it is as
It shapes the cell-rise

 

Image: The Grünenthal Group

Dr Esther Chan Wai-yin: University of Hong Kong

Assistant Professor Department Of Pharmacology And Pharmacy and Research Lead of Centre for Safe Medication Practice and Research, University Of Hong Kong: Image: Li Ka Shing Faculty of Medicine, University of Hong Kong

I saw grace in human faces in Prague in Granada in Dhaka in Rome or in
London Manchester or York and found moss on city brick walls and saw
Butterflies on squeezed in greens of tiny spaces in town gardens and saw
Waters mining for life poetry in silence music in the ferns climbing onto
The trellis of light heard seagulls’ cries as human babies in all-everyday

In everyday momentary miracles
I saw life’s rainbow biochemistry
Unfolding noughts in paperboats
It is always the same song of love
That never dies and forever lives

:Munayem Mayenin: November 07: 2015

Melatonin May Aid Cancer Patients to Prevent Chemotherapy Induced Neuropathic Pain

 

|| September 19: 2017: University of Edinburgh News || ά. Painful side effects from cancer medicines could be tackled with a drug, that eases the effects of jet lag, research suggests. The drug Melatonin appears to prevent pain, caused by chemotherapy damage to nerves. In the study it has been found to be able to block harmful effects on nerve health. The study was conducted with rats. Researchers say that the findings may help scientists understand more about the ways to limit painful side effects of chemotherapy.

Scientists from the Universities of Edinburgh and Aberdeen focused on a common condition, known as, chemotherapy-induced neuropathic pain:CINP, which causes tingling and pain sensation to touch and cold temperatures, that can be severe enough to cause patients to limit their chemotherapy treatment. CINP affects almost 70% of patients undergoing chemotherapy and can have severe impact on quality of life. Everyday activities, including, fastening buttons or walking barefoot, can cause pain, that can persist, even, after the cancer is cured, meaning that some patients are unable to return to work or able to carry out household tasks.

''This is an area of real unmet need, where new therapies are urgently required. We are actively exploring an early-phase clinical study to see if these exciting laboratory findings might translate to direct benefit for patients undergoing chemotherapy.'' says Professor Lesley Colvin, Anaesthesia, Critical Care and Pain Medicine, University of Edinburgh.

The study showed that Mlatonin, given prior to chemotherapy, limited the damaging effect on nerve cells and the development of pain symptoms. Melatonin did not alleviate pain, when CINP had already developed, suggesting that its potential benefits could be as prevention rather than cure.

Importantly, melatonin treatment did not interfere with the beneficial anticancer effects of chemotherapy in human breast and ovarian cancer cells. ''These findings are very exciting and suggest that melatonin could prevent CINP by protecting nerve cell mitochondria. Our next steps will be to further test this theory by looking at the effect of melatonin in other pain conditions that also involve mitochondrial damage.'' says Dr Carole Torsney, Centre for Integrative Physiology, University of Edinburgh.

Findings further showed that melatonin reduced damage, caused by chemotherapy to vital parts of nerve cells, known as, mitochondria. Researchers say that reducing harm to these cell energy centres could hold the key to preventing CINP.

Melatonin is a naturally occurring hormone, that controls sleeping patterns, although, synthetic versions can be produced in the laboratory. Melatonin can be used to alleviate sleep disturbance but is not available in the UK without prescription.

''These results are promising, especially, as Melatonin treatment is known to be safe in other conditions. However, more work will need to be done before we know if Melatonin will help prevent pain in cancer patients undergoing chemotherapy.'' says Professor Helen Galley, Institute of Medical Sciences, University of Aberdeen.

The study was published in the Journal of Pineal Research and was funded by the Association of Anaesthetists of Great Britain and Ireland, British Journal of Anaesthesia, the Royal College of Anaesthetists and the Melville Trust for the Care and Cure of Cancer. ω.

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Computer Algorithm Research Links Facial Masculinity to Autism Spectrum Disorder

 

 


|| August 26: 2017: University of Western Australia News || ά. A link between masculine facial features and autism has been discovered by researchers from the University of Western Australia, Telethon Kids Institute and Princess Margaret Hospital for Children. The first of its kind study used three--D photogrammetry to examine whether pre-pubescent boys and girls with an Autism Spectrum Disorder:ASD displayed more masculine features compared to those without the condition. The research has been published yesterday in Scientific Reports by the Nature Publishing Group.

Genetic factors are known to play a major role in ASD, however, there is growing evidence that hormonal factors, also, influence development of the condition. A computer algorithm designed by UWA researchers was used to generate a gender score for a sample of three-D facial images to create a scale ranging from very masculine to very feminine. The gender scores were based on an analysis for 11 facial features, such as, breadth of a person's nose, distance between the outer corners of the eyes, upper lip height and width of the mouth and were compared between an autistic group and a control group.

A total 113 girls and 102 boys, who were not autistic and 20 girls and 54 boys, who were autistic were involved in the study. For each sex, increased facial masculinity was observed in the ASD group compared to the control group.

Further analysis showed that increased facial masculinity in the group with autism correlated with more social communication difficulties as measured on the Autism Diagnostic Observation Scale. UWA Research Associate Mr Syed Zulqarnain Gilani, from UWA’s School of Computer Science and Software Engineering said that the extent of facial masculinity/femininity varied from one individual to another.

“We have developed an algorithm to measure this variation using three-D images of people, which calculates a metric for each face, which we refer to as the gender score.” Mr Gilani said. “When we applied this algorithm to three-D faces of children diagnosed with an ASD, the results and trends were fascinating.”

The study is the first to report that the faces of boys and girls with ASD are more masculinised than the faces of typically developing children, according to research associate Ms Diana Tan, from UWA’s School of Psychological Science.

“In our previous research, we found that a more masculinised facial profile was associated with increased exposure to prenatal testosterone.” Ms Tan said. “The current findings highlight a possible connection between prenatal testosterone and ASD.

A facial characteristic that is unique to ASD provides potential biological markers for this condition. In the long run, we hope to further explore the possibility for three-D facial images to be used as a complementary diagnostic tool to aid in the early identification of ASD.''
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How Goldfish Make Alcohol to Survive Without Oxygen

Image: University of Liverpool

 

|| August 11: 2017: University of Liverpool News || ά. Scientists at the Universities of Liverpool and Oslo have uncovered the secret behind a goldfish’s remarkable ability to produce alcohol as a way of surviving harsh winters beneath frozen lakes. Humans and most other vertebrate animals die within a few minutes without oxygen. Yet, goldfish and their wild relatives, crucian carp, can survive for days, even months, in oxygen-free water at the bottom of ice-covered ponds. During this time, the fish are able to convert anaerobically produced lactic acid into ethanol, which then diffuses across their gills into the surrounding water and avoids a dangerous build-up of lactic acid in the body.

The molecular mechanism behind this highly unusual ability, which is unique among vertebrates and more commonly associated with brewer’s yeast, has now been uncovered and is published in the journal Scientific Reports. The international research team has shown that muscles of goldfish and crucian carp contain not just the usual one, but two sets of the proteins, normally, used to channel carbohydrates towards their breakdown within a cell’s mitochondria, a key step for energy production.

While one set of these proteins appears very similar to that in other species, the second set is strongly activated by the absence of oxygen and shows a mutation that allows channelling of metabolic substrates to ethanol formation outside the mitochondria.

Further genetic analyses suggest that the two sets of proteins arose as part of a whole genome duplication event in a common ancestor of goldfish and crucian carp some eight million years ago.

Dr Michael Berenbrink, an Evolutionary Physiologist at the University of Liverpool, said, “During their time in oxygen-free water in ice-covered ponds, which can last for several months in their northern European habitat, blood alcohol concentrations in crucian carp can reach more than 50 mg per 100 millilitres, which is above the drink drive limit in these countries.

However, this is still a much better situation than filling up with lactic acid, which is the metabolic end product for other vertebrates, including, humans, when devoid of oxygen.”

Lead Author Dr Cathrine Elisabeth Fagernes, from the University of Oslo, said, “This research emphasises the role of whole genome duplications in the evolution of biological novelty and the adaptation of species to previously inhospitable environments.

The ethanol production allows the crucian carp to be the only fish species surviving and exploiting these harsh environments, thereby, avoiding competition and escaping predation by other fish species, with which, they normally interact in better oxygenated waters.

It’s no wonder then that the crucian carp’s cousin, the goldfish, is arguably one of the most resilient pets under human care.” The work is the result of a collaboration between scientists at the University of Liverpool, UK and the University of Oslo, Norway. The work was funded by the Research Council of Norway.
ω.

The Paper: Extreme anoxia tolerance in crucian carp and goldfish through neofunctionalization of duplicated genes creating a new ethanol-producing pyruvate decarboxylase pathway, is published in Scientific Reports.
DOI: 10.1038/s41598-017-07385-4

Whatever Your Field of Work and Wherever in the World You are, Please, Make a Choice to Do All You Can to Seek and Demand the End of Death Penalty For It is Your Business What is Done in Your Name. The Law That Makes Humans Take Part in Taking Human Lives and That Permits and Kills Human Lives is No Law. It is the Rule of the Jungle Where Law Does Not Exist. The Humanion

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Protein Fibres: You are Looking at the Principles on Which the Mechanism is Constructed

New study simulates the formation of protein fibres and suggests, contrary to other studies, that these structures all follow a general physical principle.
Image: Martin Lenz and Thomas Witten
 

|| July 17: 2017: University of Chicago News: Carla Reiter Writing || ά. Alzheimer’s disease results from a dysfunctional stacking of protein molecules, that form long fibres inside brain cells. Similar stacking occurs in Sickle-Cell Anaemia and Mad Cow Disease. Scientists know these orderly fibres develop from a wide variety of molecules, but could there be a common reason as to why they form? In new research, physicists at the University of Chicago and Université Paris-Saclay suggest that such protein fibres are a manifestation of a general physical principle.

And that principle offers the possibility of new medicines and tools for engineering desirable protein structures. The findings were published earlier this month in Nature Physics. “We have strong evidence that there’s a principle shaping how things aggregate, that can be used both to understand disease and modify it and to make things self-assemble in a way that we dictate.” said Co-author Professor Thomas Witten, the Homer J. Livingston Professor Emeritus of Physics at the University. Proteins aggregate all the time. But mostly they make amorphous blobs similar to those in egg drop soup.

“We’re trying to find out what makes some molecules assemble to form a fibre, instead of a glop.” Professor Witten said. The proteins, that form fibres are identical but irregular; they don’t fit together cleanly. Professor Witten and his collaborator Mr Martin Lenz, a researcher at Université Paris-Saclay, wondered if that irregularity, might, hold a key to fibre formation.

Using computers, Mr Lenz, Lead Author of the study, devised a mathematical model to simulate how identical but ill-fitting objects would clump together. He used pentagons and other simple polygons to represent the irregular, fibre-forming proteins. “We didn’t have a lab and test tubes. We just had these little shapes.” said Professor Witten.

The researchers made the interaction of the polygons depend on just two attributes without incorporating any other features of real molecules. As in a real fibre, all of the sub-units are identical and irregular. They are, also, what Professor Witten calls 'sticky', they attract each other but they don’t feel the attraction until they touch. They 'want' to touch and they gain energy if they do. ''But because the shapes don’t fit together cleanly, their surfaces can’t touch and feel the stickiness and get that energy unless they distort.” Professor Witten said.

Their propensity is to elongate themselves, as much as possible, to maximize the amount of their surface, .that is in contact. “But distortion costs them energy. They have to exert forces to get the surfaces to meet. So, there is a competition between the energy gained by sticking and the energy cost of distortion.'' Professor Witten said.

 The simulations done by Mr Lenz embodied that competition. The shapes could attach along any surface. The scientists varied the degree of stickiness relative to the energy cost of distortion for each shape and looked at the various structures, that formed across the range of values. The results were striking: No matter what shape they used, when stickiness and the energy cost of distortion were more or less equal, they got fibres every time.

An additional feature was needed to form the fibres. The growth needed to be irreversible with every surface, that sticks needing to stay stuck. Without this irreversible feature, often seen in real molecules, the long fibres would eventually melt into roundish blobs. The research differs from the approach taken by scientists, who study the diseases caused by protein fibres. “They have done a lot of work on the particulars of the molecules involved and there are strongly held ideas about how those particulars cause the fibres to form.” Mr Lenz said.

“We’re saying, ‘You don’t need a specific molecule: it’s a general principle.’ They’re skeptical about that, but despite their skepticism, they acknowledge that our idea deserves a hearing.” Professor Witten said.

So far, Mr Lenz and Professor Witten have tried only a small array of shapes in two dimensions. They plan to try to see if the principle holds true for arbitrary shapes, in three dimensions and abstract the essence of what’s going on in the simulations.

“We want to have a theory, that predicts things, that we can then verify on the computer; a theory, that doesn’t use specific features of a particular particle shape but just uses the stickiness and the distortion.” said Professor Witten.

“We, may be, able to prevent the mad-cow and the sickle cell fibres, if we understand this principle. And we should be able to use the principle to make fibres when they are beneficial. Just put in the right stickiness, put in the right distortion, adjust everything and get the fibres we want. ω.

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Looking for Photosynthetic Breakthrough to Increase Yields in Crops

 

|| July 04: 2017: University of Essex News || ά. A researcher at the University of Essex has uncovered secrets about a protein, which could help feed the growing global population. Professor Christine Raines,, working with scientists at the Carl R Woese Institute for Genomic Biology Photosynthesis at the University of Illinois investigated the protein CP12, which could boost crop yields in the future. Photosynthesis is one of the most complicated and important processes responsible for kick-starting Earth’s food chain. While researchers have modelled its more-than-100 major steps, scientists are still discovering the purpose of proteins that can be engineered to increase yield.

Related research was published in Science last year. There are three forms of the protein CP12 that regulate the enzymes GAPDH and PRK. The enzymes are the workhorses while CP12 holds the reins. CP12 tells them to get to work when there’s light and reins them in when it’s dark. “CP12 is an important component because it helps plants respond to changing light levels, for example when the plant is shaded by a leaf or cloud.” said First Author Dr Patricia Lopez, a postdoctoral researcher for Realising Increased Photosynthetic Efficiency:RIPE, who led the research. “CP12 stops the activity of the enzymes within seconds but without CP12, it will take several minutes to slow the activity, costing the plant precious energy.”

Published in the Journal of Experimental Botany,Dr Lopez and co-authors found not all CP12 enzymes are created equal. In fact CP12-3 is not part of this process, whereas CP12-1 and CP12-2 are in charge and can cover for each other. Get rid of all three, and the plant can’t photosynthesize efficiently, resulting in a drastically smaller plant with fewer, smaller seeds.

In fact, without CP12 to hold the reins, PRK also disappears. “PRK is a vital workhorse, that provides the raw materials for the enzyme Rubisco to turn into carbohydrates, the sugars the plant uses to grow bigger and produce more yield.” said Lead Author Professor Christine Raines, a Professor of Plant Molecular Physiology.

Agriculture is approaching the limits of the yield traits that drove the remarkable yield increases over the past century, said RIPE Associate Director Don Ort, USDA:ARS scientist and the Robert Emerson Professor of Plant Biology at the Carl R Woese Institute for Genomic Biology. “Improving photosynthesis has the promise of being the next frontier to dramatic boost crop yields and for the first time there is both a molecular understanding of photosynthesis and powerful technological tools to make engineering photosynthesis a realistic and attainable goal.”

The paper 'Arabidopsis CP12 mutants have reduced levels of phosphoribulokinase and impaired function of the Calvin–Benson cycle' is published by the Journal of Experimental Botany. Co-authors include Amani Omar Abuzaid and Professor Tracy Lawson.

RIPE is an international research project engineering plants to more efficiently turn the sun’s energy into food to sustainably increase worldwide food productivity. The RIPE project is supported by the Bill and Melinda Gates Foundation. The Carl R. Woese Institute for Genomic Biology advances life sciences research through interdisciplinary collaborations within an advanced genomic research facility at the University of Illinois.
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Whatever Your Field of Work and Wherever in the World You are, Please, Make a Choice to Do All You Can to Seek and Demand the End of Death Penalty For It is Your Business What is Done in Your Name. The Law That Makes Humans Take Part in Taking Human Lives and That Permits and Kills Human Lives is No Law. It is the Rule of the Jungle Where Law Does Not Exist. The Humanion

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Food and Nutritional Research Improves Cancer Survival Rates

Image: Jim Coughlan

 

|| July 01: 2017: University College Cork News || ά. Up to 80% of cancer patients unintentionally lose weight, which can have a devastating impact on their quality of life, according to Dr Aoife Ryan, Dietitian and Lecturer in Nutritional Sciences at UCC.  The weight loss reduces their ability to tolerate chemotherapy and leading to poor survival rates. The seriousness of this issue is illustrated by the fact that one in five cancer deaths are caused from wasting, not from cancer. The wastage affects not just the muscles involved in movement but also the muscles involved in breathing and in the heart. Dr Ryan says, ''Unfortunately, there is no safe drug to prevent or reverse this or to safely stimulate appetite.''

It seems it is almost the norm to lose weight once you develop cancer. Ten years ago it was thought patients were losing fat. Now we can use their CT scans to measure exactly what patients are losing and we are gaining a huge understanding that that weight loss is actually muscle. It is the rapid loss of muscle.” A great example of how the roles of nutritionists and food scientists can help cancer patients can be seen from current research at UCC into the development of innovative protein gels, dietary drinks and appetite-increasing supplements to assist cancer patients who are experiencing involuntary and at times life-threatening weight loss.

Cancer patients often develop severe muscle wasting, called, ‘sarcopenia', which is most commonly seen in very elderly people and is an inevitable consequence of growing very old. Sarcopenia means a very low muscle mass, <5th centile. In cancer, it develops much more rapidly and at much younger ages. ''I have seen cancer patients with a normal muscle mass at diagnosis and two months later they are sarcopenic, while severe muscle loss is very common in patients, it isn’t always hugely visible as a person can still be overweight or even obese.'' says Dr Ryan.

Dr Ryan’s team of nutritional scientists at UCC have performed a detailed study of the nutritional status and quality of life in ambulatory Irish cancer patients attending for chemotherapy at Cork University Hospital and the Mercy University Hospital. In a study which has been on-going since 2011, 1,020 patients have been recruited to date. "We have looked at over a thousand patients having chemotherapy here in Cork and only 4% of them look underweight. We rarely see obviously wasted cancer patients anymore, nowadays they look normal or overweight but, underneath that fat, there is very little muscle. Over 40% have sarcopenia and these patients live about half as long as people who maintain their muscle."

It is known that protein intake is of fundamental importance in this regard, and so she is looking at ways to increase this intake and also to address why patients are losing weight in the first place. "They are losing weight because cancer causes huge amounts of inflammation in their bodies. So can we dampen down inflammation which would cause them to stop losing weight? If they are weight stable they will live longer."

Towards this goal, Dr Ryan has spent over 12 years studying the fish oil, EPA, which is found in salmon, mackerel and herring. Unfortunately, most people eat very little of it. To provide new means of incorporating EPA into the diet, nutritionists at UCC have joined forces with food scientists to put a high dose of fish oil into a nutritional drink. Dr Ryan says the results to date have been encouraging.

“Several clinical trials have shown that, if we give patients with cancer calories, protein and a very high dose of a fish oil, that it will dampen down inflammation and they will lose less muscle. Keeping patients active through exercise is also hugely important.”  As part of this work, Dr Ryan develops products in conjunction with colleagues including Dr Shane Crowley and Professor Alan Kelly of the School of Food and Nutritional Sciences at UCC. Professor Kelly says that this work is a perfect example of where a complementary relationship between Nutrition and Food Science can deliver hugely important outcomes.

“Food Scientists have the skills to develop products the design of which has been informed by the nutritional understanding of what food does to the body and, in this case, the particular issues of cancer patients are that we hope to solve. But there might be other considerations to do with the texture or the structure, for example in terms of chewing and swallowing and digestibility or flavour.

So the food scientist says “How do we design that product? How do we mask flavour? Any product is ingredients plus a process we apply to it, so food scientists will find the right ingredients for the product properties that are needed and work out a way to turn these into a desirable, safe and high-quality product.” Meanwhile, food scientists at UCC are, also, developing high protein gels for cancer patients, based on the fact that patients undergoing chemotherapy often suffer from metallic tastes in their mouths so they have taste challenges as well as appetite challenges.

The gels would be tasteless and could be added in to food without affecting texture and yet deliver critical nutrients and taste sensations tailored to the sensory perceptions of cancer patients. Scientists at UCC working as part of the national Food for Health Ireland consortium have also found small peptides, released from proteins from milk that can mimic the action of hunger hormones in the body. Initial studies in animals conducted at UCC showed increased food intake when given these peptides. Dr Ryan says that they have now encapsulated the peptides for trials in healthy humans to examine bioactivity and these, may, eventually be trialled in diseased populations including cancer.

“They take it in a capsule and it is released in the small intestine. And then it has actions there where we think it will stimulate appetite. If trials are positive it would represent a safe way of stimulating appetite.” The food industry of the future, delivering products which meet the needs of the healthy and sick, will depend on the skills of graduates from programmes such as the four-year BSc programmes in Food Science and Nutritional Science at UCC.

There is a huge demand for food science and nutritional graduates with over 93% of Food Science and Nutritional graduates in full-time employment or doing post-graduate courses according to the First Destination of UCC Graduates Survey 2015. ω.

Whatever Your Field of Work and Wherever in the World You are, Please, Make a Choice to Do All You Can to Seek and Demand the End of Death Penalty For It is Your Business What is Done in Your Name. The Law That Makes Humans Take Part in Taking Human Lives and That Permits and Kills Human Lives is No Law. It is the Rule of the Jungle Where Law Does Not Exist. The Humanion

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Hydrogen Peroxide Protects Plants Against Sun Damage


 

|| June 30: 2017: University of Exeter News || ά. Plants use hydrogen peroxide:H2O2, best known for use in bleach and hair treatments, to control how their cells react to varying levels of light, new research shows. The chemical is a by-product of photosynthesis in parts of plant cells, called, chloroplasts. The signalling role of hydrogen peroxide had previously been suspected, but this study, by the University of Exeter and the University of Essex, is the first to discover where and how it happens.

Using a fluorescent protein, that detects hydrogen peroxide, the researchers observed how H2O2 moves from chloroplasts and can be detected in cell nuclei. Plants’ genes are located in the nuclei and the process discovered, shows how plants activate the genes needed for the leaves to adapt to the potentially damaging effects of bright light. This process of chloroplasts communicating with the nucleus ensures that plants continue to protect photosynthesis and adjust to prevailing conditions. Photosynthesis in crop plants determines how well they grow and yield. The scientists, also, found that some of the chloroplasts, which produce the H2O2 signal are attached to the cell nucleus, allowing them to pass the chemical effectively.

“It’s important for plants to be able to detect how much light there is, so they can make the most of it for photosynthesis.” said Professor Nick Smirnoff, of the University of Exeter. ''They, also, have to adjust to protect themselves, as high levels of light can damage leaves, similar in some ways to how we humans get sunburn on our skin.”

Professor Phil Mullineaux, of the University of Essex, said, “We know that there are a lot of different signals sent to cell nuclei to switch on genes and reorganise the way cells work, but this is the first time these signals have been observed moving from the chloroplasts, where photosynthesis takes place, to the nucleus.”

Lead Author Dr Marino Exposito-Rodriguez, formerly of the University of Exeter but now at the University of Essex, said, “This breakthrough was made possible by the development of the hydrogen peroxide fluorescent protein sensors, which allowed us to observe the movement of H2O2 in plant cells in real time.”

The paper, published in the journal Nature Communications: 'Photosynthesis-dependent H2O2 transfer from chloroplasts to nuclei provides a high-light signalling mechanism'. The study was funded by the UK Biotechnology and Biological Sciences Research Council:BBSRC.
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Whatever Your Field of Work and Wherever in the World You are, Please, Make a Choice to Do All You Can to Seek and Demand the End of Death Penalty For It is Your Business What is Done in Your Name. The Law That Makes Humans Take Part in Taking Human Lives and That Permits and Kills Human Lives is No Law. It is the Rule of the Jungle Where Law Does Not Exist. The Humanion

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New Research Improves Understanding of Cellular Ageing and Cancer Development

 

|| June 25: 2017: National University of Singapore || ά. A team of researchers led by Dr Dennis Kappei, a Special Fellow from the Cancer Science Institute of Singapore:CSI Singapore at the National University of Singapore:NUS, has discovered the role of the protein ZBTB48 in regulating both telomeres and mitochondria, which are key players involved in cellular ageing. The results of the study will contribute to a better understanding of the human ageing process as well as cancer development.

The study, which was conducted in collaboration with researchers at the TU Dresden and the Institute of Molecular Biology Mainz, both in Germany, were published in the journal EMBO Reports in May 2017. In vertebrates, telomeres act as protective caps located at the ends of chromosomes. Telomeres shorten every time a cell divides, and ultimately, the loss of telomeres leads to cellular senescence, where cells cease to divide and eventually, cell death. Cancer cells are known to bypass this limit by activating mechanisms, that keep their telomeres long, thereby, allowing for their unlimited proliferative potential.

Previous studies have linked telomeres to the function of mitochondria, essential cell organelles, that act as cellular power plants and vice versa. ZBTB48 has recently been found to directly bind to telomeres, that are abnormally long and to limit them from growing further. It is only the fourth protein, that is known to bind to telomeres. The first two proteins, TRF1 and TRF2, had been discovered about two decades ago, while previous research work by Dr Kappei had discovered the third, HOT1, only in 2013.

In this study, the research team found that ZBTB48 not only prevents further telomere lengthening in cells, that already have abnormally long telomeres, but more generally, in cancer cells, regardless of their telomere length. In addition, the team uncovered that ZBTB48 can activate the production of a specific set of genes, which include a mitochondrial gene, called, MFTP1.

“The findings from our study validated recent findings on the telomere binding role of ZBTB48. Our team’s independent discovery of the ZBTB48 protein is an extension to these recent findings, as we found evidence indicating that cancer cells, in general, are regulated by ZBTB48.

It potentially, also, suggests applications for the human ageing process even at old age when telomere length has already decreased,” said Dr Grishma Rane, Research Fellow at CSI Singapore and co-first author of the study.

The team is looking deeper into the role of the ZBTB48 protein in both cancer development and ageing. Dr Kappei said, “We are now actively pursuing the exact molecular mechanism, through which ZBTB48 controls telomere length, and further looking into ZBTB48’s role in various cancers, such as, neuroblastoma, in which the gene is frequently deleted.

With the discovery of ZBTB48’s novel linkage between telomeres and mitochondria, which both have key roles in cellular ageing, we will, also, be studying whether this interplay contributes to telomere maintenance.” The research was supported by the National Medical Research Council of Singapore, the National Research Foundation Singapore and the Singapore Ministry of Education. ω.

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I am the Scent: Can You Hear Me

 

|| June 25: 2017: University of Leuven News || ά. Research with mice has showed new insights into how we determine where a scent comes from. The rodents seem to do this by comparing stimuli from both nostrils. The mechanism is similar to how we locate a sound source. Most mammals can quickly and easily determine where a scent is coming from. How our brains provide us with this information, however, is still a big question.

That’s why a research team from Neuro-Electronics Research Flanders:NERF, a collaboration between VIB, KU Leuven and IMEC set up an experiment with mice, masters at recognising scents. The NERF team, led by Professor Sebastian Haesler, developed a new method to measure scent movements. By using an infrared camera, they were able to work in an animal friendly way, without invasive techniques. The research showed that mice could direct their nose to a new scent extremely quickly: in fewer than 100 milliseconds.

“Our research shows that mice compare the strength of the scent in both nostrils, which allows them to pinpoint the direction of the scent source.” says Professor Haesler. “This process, also, involves the transfer of information between both cerebral hemispheres. The mechanism strongly resembles the way, in which, we localise a sound source.

The cells in the brain stem, that localise sound do this by waiting for and comparing the different signals from both ears. We have, also, identified the part of the brain, that processes scent information.”

Professor Haesler and his team are now researching the transfer of information between both cerebral hemispheres to find out exactly how scent localisation in our brains works. At the same time, they will apply this information in the context of Alzheimer’s research.

“Our mice only reacted to new scents. But a mouse with Alzheimer's will probably, also, react to familiar but forgotten scents. Alzheimer's is often associated with the loss of one's sense of smell, for that matter. Consequently, research on scent recognition is very important to better understand memory disorders.” ω.

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There Exists Nothing in This Universe Without a Purpose: The Role of Vitamin A in Diabetes

Image: Sara Liedholm

 

|| June 21: 2017: Lund University News || ά. There has been no known link between diabetes and vitamin A, until now. A new study suggests that the vitamin improves the insulin producing β-cell´s function. The researchers initially discovered that insulin-producing beta-cells contained a large quantity of a cell surface receptor for vitamin A. “There are no unnecessary surface receptors in human cells. They all serve a purpose but which, in many cases, is still unknown and because of that they are called , orphan' receptors.

When we discovered that insulin cells had a cell surface expressed receptor for vitamin A, we thought it was important to find out why and what the purpose was of a cell surface receptor interacting with vitamin A mediating a rapid response to vitamin A.” explains Mr Albert Salehi, senior researcher at the Lund University Diabetes Centre in Sweden. The researchers believe that the purpose, in this particular case, is that vitamin A plays an important role for the development of beta-cells in the early stages of life; but also, for a proper function during the remaining life, especially, during pathophysiological conditions, i.e some inflammatory conditions.

Mr Albert Salehi and his research team, together with their colleagues at the University of Gothenburg, King’s College London and the Oxford Centre for Diabetes, have mapped 220 different receptors on the surface of the beta cell, whose features are still not fully known. One of the findings is the cell surface expressed receptor for vitamin A. In order to study the role of the vitamin in cases of diabetes, the researchers worked with insulin cells from mice and non-diabetic and type two diabetic donors. By partially blocking the vitamin A receptor and challenging the cells with sugar, they could see that the cells’ ability to secrete insulin deteriorated.

“We saw close to a 30 per cent reduction.” says Mr Albert Salehi, adding that impaired cell survival and insulin secretion are key causes of type two diabetes. The same tendency could be seen when comparing insulin cells from type two diabetic donors. Cells from patients with type two diabetes were less capable of insulin secretion compared with cells from people without diabetes.

The researchers, further, saw that the beta-cells’ resistance to inflammation decreases in the absence of vitamin A. In case of a complete deficiency, the cells die. The discovery, may be, significant for certain types of type one diabetes when the beta-cells are not sufficiently developed during the early stages of life. “In animal experiments it is known that newborn mice need vitamin A to develop their beta-cells in a normal way. Most likely, the same applies to human beings. Children must absorb a sufficient amount of vitamin A through their diet.”, says Mr Salehi.

Vitamin A is found mainly in offal and dairy products. In Sweden, milk is enriched with vitamin A. There appears to be no vitamin A deficiency in Sweden in people, who eat a standard variety of food; but vegetarians perhaps need to be aware of the problem. Too much vitamin A is harmful and can lead to osteoporosis. However, there is no risk of excessive intake through food, the risk lies in taking dietary supplements. Defects associated with vitamin A deficiency are, among other things, impaired night vision and reduced elasticity in the skin and mucous membranes.

In the event of a diabetes treatment, based on the newly found cell surface receptor for vitamin A, Mr Salehi believes that the risk of excessive intake makes the vitamin A itself inappropriate. “But we’re trying to find substances such as small molecules or peptides, that are similar to the vitamin A could activate the newly found receptor while lacking the unwanted effects of vitamin A.”  he concludes.
ω.

Publication: Anti-diabetic action of all-trans retinoic acid and the orphan G protein coupled receptor GPRC5C in pancreatic β-cells

Contact: Albert Salehi, researcher and associate professor of pharmacology, Lund University: +46 708 65 91 79: s_albert.salehi at med.lu.se

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Childhood Obesity Causes Lasting Damage to the Body

 

 

|| June 16: 2017: University of Surrey News: Natasha Meredith Writing || ά. Examining data collected from over 300,000 participants across 18 studies, researchers from the University of Surrey identified increased arterial damage and enhanced likelihood of pre diabetes in participants who were obese in childhood. The damage, an increased thickness of these vital arteries, heightens the likelihood of an individual suffering from a cardiovascular ailment, such as heart disease, in later life.

Body mass index:BMI, waist circumference and skin fold thickness measurements of over 300,000 children, average age of 10, were assessed and compared with results gathered from the same participants on average 25 years later. Researchers discovered that obese children were pre disposed to ‘pre-diabetes’, an inability to adequately metabolise glucose, which can later lead to diabetes and thickening of arteries in adulthood, both of which can be detrimental to their adult health.

Childhood BMI, also, proved to be an indicator of adult hypertension demonstrating that this indicator is useful in predicting illnesses associated with obesity in adulthood. Due to limited data it is unknown if waist circumference and skin fold thickness are indicators to future ailments.

Childhood obesity has become increasingly prevalent in the UK, with figures from the NHS National Child Measurement Programme indicating that 19.8 per cent of 10-11 year olds being classed as obese in 2015:16, a rise of 0.7 per cent on the previous year. The long term implications of childhood obesity to adult health and resulting cost to the NHS is unknown.

Lead author Dr Martin Whyte from the University of Surrey, said, “It is worrying that obesity is becoming endemic in our society.

“The adverse effects of adult obesity are well known but what we have found is that obesity in childhood can cause lasting arterial damage which could potentially lead to life threatening illness. This is something that we need to address to protect adult health and reduce pressure on the NHS.”ω.

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Scientists Develop Molecular Code for Melanin-Like Materials

Image: University of Strathclyde

 

|| June 12: 2017: University of Strathclyde News || ά. Scientists have long known melanin, the pigments that give colour to skin, hair and eyes, has numerous useful qualities, including providing protection from cancer-causing ultraviolet:UV radiation. Due to its inherently disordered structure, however, attempts at recreating it in the laboratory have been thwarted. Now a group of scientists, including researchers from the University of Strathclyde and City University of New York:CUNY, have developed a new approach for producing materials that not only mimic the properties of melanin, but also provide unprecedented control over them.

The discovery, published in the journal Science, could enable the development of new cosmetic and biomedical products. Melanin is best-known for its role in giving colour to the skin and protecting it against the sun’s harmful rays but it also has other qualities, including electronic conductance, adhesiveness and the capacity to store energy. Unlike other biopolymers, such as DNA and proteins, where a direct link exists between the polymers’ ordered structures and their properties, the structure of melanin is inherently disordered.

As a result directly relating structure to function is not possible, meaning researchers have been unable to fully exploit melanin’s properties. To overcome this the research team used simple version of proteins, tripeptides consisting of just three amino acids, to produce molecular architectures with precisely controlled levels of order and disorder.

Lead Researcher Professor Rein V. Ulijn, Director of the Nanoscience Initiative at the Advanced Science Research Centre:ASRC at the Graduate Centre, CUNY, said, “We were amazed to see that, upon oxidation of these peptide structures, polymeric pigments with a range of colours, from light beige to deep brown, were formed.”

Subsequent, in-depth characterisation of the approach demonstrated that further properties, such as UV absorbance and nanoscale morphology of the melanin-like materials, could also be systematically controlled by the amino acid sequence of the tripeptide.

Dr Tell Tuttle, Director of Research in the Department of Pure and Applied Chemistry at Strathclyde, employed computational technologies to characterise these materials and understand how these different structures could be created from the smaller building blocks of tripeptides.

He said, “Through our ability to control the structures formed by tripeptides we’ve created materials that display the various properties of melanin but which we can shape as we wish. This project combined the ASRC’s world-class facilities and experimental expertise with our computational expertise and the ARCHIE-WeSt supercomputer based at Strathclyde to produce materials that in many ways are better than melanin due to the control that we can exercise over them.”

The findings published in Science build on previous research conducted by Professor Ulijn, who is, also, the Albert Einstein Professor of Chemistry at Hunter College and a member of the biochemistry and chemistry doctoral faculty at the Graduate Centre.

His lab will now turn its attention to further clarifying the chemical structures that form and expanding the resulting functionalities and properties of the various melanin-like materials they produce. The researchers are also pursuing commercialisation of this new technology, which includes near-term possibilities in cosmetics and biomedicine.

Funding for the research was provided in part by the US Air Force. Additional funding was provided by the Israeli Council of Higher Education, Postdoctoral Fellowship. ω.

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Delaying Meals Impacts on Sugar Levels in the Body


 

|| June 05: 2017: University of Surrey News: Natasha Meredith Writing || ά. In the first human study of its kind, researchers from the University of Surrey discovered that delaying meal times delays the circadian rhythm of sugar in the blood. The findings could prove to be a breakthrough in alleviating symptoms of jet lag and shift work, a new study in the journal Current Biology reports. During this innovative study, Dr Jonathan Johnston and Dr Sophie Wehrens from the University of Surrey examined the impact of altering meal times on the circadian rhythms of ten volunteers.

Circadian rhythms are approximately 24-hour changes governed by the body’s internal clocks and determine many physiological processes in the body. Volunteers were provided with three meals breakfast, lunch and dinner. In the first phase of the study, the first meal was provided 30 minutes after waking, with later meals at subsequent five hour intervals whilst in the second phase each meal was delayed by five hours after waking.

Immediately after each phase, sequential blood samples and fat biopsies were taken from each volunteer in specialised laboratory conditions, that allow measurement of internal circadian rhythms. Researchers discovered that postponing meal times by five hours delayed rhythms of blood sugar by the same time frame. This discovery demonstrates that mealtimes synchronise internal clocks, that control rhythms of blood sugar concentration.

Researchers indicated that people, who struggle with circadian rhythm disorders, including shift workers and long haul flights, might consider timed meals to help resynchronise their body clocks.

Surprisingly, researchers uncovered that the delay in meal times did not affect insulin or triglyceride:fat levels in the blood indicating that blood sugar rhythms can be governed by separate circadian clocks to these other key aspects of rhythmic metabolism.

Lead investigator of the study, Dr Jonathan Johnston, from the University of Surrey, said, “It has been shown that regular jet lag and shift work have adverse effects on the body, including metabolic disturbances.

“Altering meal times can reset the body clocks regulating sugar metabolism in a drug free way. This will help us design feeding regimes to reduce the risk of developing health problems such as obesity and cardiovascular disease in people with disturbed circadian rhythms.” ω.

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How RNA Formed at the Origins of Life

New species of gastropod snail Phymorhynchus n. sp. Image: David Shale: University of Southampton



|| May 24: 2017: UCL News || ά. A single process for how a group of molecules called nucleotides were made on the early Earth, before life began, has been suggested by a UCL-led team of researchers. Nucleotides are essential to all life on Earth as they form the building blocks of DNA or RNA, and understanding how they were first made is a long-standing challenge that must be resolved to elucidate the origins of life. In a study, published in Nature Communications and funded by the Engineering and Physical Sciences Research Council, the Simons Foundation and the Origins of Life Challenge, researchers from UCL, Harvard University and Massachusetts General Hospital suggest a single chemical mechanism by which both classes of nucleotides – purines and pyrimidines – could have formed together.

Before now, scientists thought that the two classes of nucleotide must have been made separately and under mutually incompatible conditions. This study is the first to show that both purines and pyrimidines can be formed from a common precursor molecule that existed before life began. “We provide a new perspective on how the original RNA molecules were made and suggest a simple chemical solution for delivering both purine and pyrimidine nucleotides at the origins of life.” explained corresponding author, Dr Matthew Powner, UCL Chemistry.

“RNA is the corner stone of all life on Earth and probably carried the first information at the outset of life, but making RNA requires both purine and pyrimidine nucleotides to be simultaneously available. A solution to this problem has remained elusive for more than 50 years.”

The team demonstrated how purines and pyrimidine nucleotides can both be assembled on the same sugar scaffold to form molecules called ribonucleotides which are used to construct RNA. Purine and pyrimidine nucleotides are used to create the DNA and RNA.

The purine and pyrimidine nucleotides bind to one another through specific molecular interactions that provide a mechanism to copy and transfer information at the molecular level, which is essential for genetics, replication and evolution. Therefore understanding the origins of nucleotides is thought to be key to understanding the origins of life itself.

The team discovered that molecules, called 8-oxo-adenosine and 8-oxo-inosine, which are purine ribonucleotides, can be formed under the same chemical conditions as the natural pyrimidine ribonucleotides. They also found that one chemical precursor can divergently yield both purine and pyrimidine ribonucleotides.

“The mechanism we’ve reported gives both classes of molecule the same stereochemistry that is universally found in the sugar scaffold of biological nucleic acids, suggesting that 8-oxo-purine ribonucleotides may have played a key role in primordial nucleic acids.” said Dr Shaun Stairs, UCL Chemistry, first author of the study.

The team now plans to further investigate mechanisms that use 8-oxo-purines to transfer information, which could help scientists better understand life’s first informational transfer systems. ω.

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Enzyme Indicators Proven as Viable Alternative for Hydrogen Peroxide Decontamination Validation

 

|| May 21: 2017 || ά. Enzyme Indicators:EIs have been proven as a revolutionary viable alternative to biological indicators:BIs for Hydrogen Peroxide decontamination validation. A white paper published on May 19 by the Parenteral Drug Association:PDA Journal of Pharmaceutical Science and Technology, and written by Public Health England:PHE, states that Enzyme Indicators are a 'potentially valuable tool for rapid VPHP bio-decontamination cycle development and subsequent re-qualification'. The paper, entitled, 'Evaluation of novel process indicators for rapid monitoring of hydrogen peroxide decontamination processes', explains the process of comparing Enzyme Indicator performance against the current industry standard approach of using biological indicators:BIs.

Given ongoing concerns about the reliability and response time of BI's, PHE explored the potential for an enzyme-based approach decontamination process evaluation. The Enzyme Indicator is based on thermostable Adenylate Kinase, an enzyme whose presence and activity can be rapidly measured by luminescence assays. This enzyme, unlike many proteins, is very thermostable and resistant to oxidizing agents. It has a very predictable biphasic inactivation profile. These characteristics make it suitable for monitoring and quantification of oxidation decontamination processes such as VH2O2.

Indicators with thermostable Adenylate Kinase:tAK, once processed, are used to catalyse a biochemical reaction with Luciferin:Luciferase. Such a reaction produces bioluminescence instantaneously. The individual photons of light produced by this reaction are recorded with a special Lunometer and an accurate measure of the degree of inactivation of the tAK indicator is achieved.

Protak Scientific are the globally exclusive licensee of this technology for gaseous decontamination validation with PHE and are working hard to educate pharmaceutical manufacturing companies about how Enzyme Indicators can benefit them from the Bio-technician to the CFO.

Mr Phillip Godden, CEO, Protak Scientific explains, “The Enzyme Indicator is a surrogate of the Biological Indicator, Geobacillus Stearothermophilus. In order to check their reliability, they can initially be combined with Biological Indicators, both for cycle development and for validation. Once validation is concluded and its reliability verified, this new technology offers three great advantages.

It gives quantitative results, one test offering a scale of <2.5log to >9log, for example a degree of reduction i.e. Log 06.55 reduction. It is instantaneous, amazingly in less than three seconds and Enzyme Indicators do not suffer rogue syndrome. No false positives, in fact, EI technology offers positive and negative controls!

The Enzyme Indicators provide immediate and quantitative proof that the decontamination cycle has achieved the expected results. And this is a game-changing revolution that radically transforms decontamination validation as we know it. The Net result? This could potentially save pharmaceutical manufacturers millions of dollars per year, thousands of hours, reduce risk, remove a run to fail process and increase process understanding instantly.” ω.

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New Research Offers Lung Therapy Hope for Critical Illness

Image: The Institution of Engineering and Technology:IET


|| May 08: 2017: University of Edinburgh News || ά. Scientists have pinpointed a chemical signal, that worsens inflammation linked to a life-threatening lung condition.The discovery could eventually lead to new therapies for the disease, which can be fatal for up to half of those affected. Acute Respiratory Distress Syndrome:ARDS is caused by widespread inflammation in the lungs and can lead to fluid leaking into the airways.

Researchers found that patients with ARDS had high levels of a type of molecule, called, mitochondrial formylated peptide in the fluid of their lungs. Laboratory tests found that these molecules played a key role in attracting specialised immune cells, neutrophils. Neutrophils are known to be responsible for orchestrating the inflammation associated with ARDS.

Studies with mice found that blocking the molecules’ signalling mechanisms helped to stem neutrophil infiltration and alleviated lung inflammation associated with ARDS. Experts at the University of Edinburgh say that the findings could pave the way for new therapies for the condition, which is currently untreatable.

''For the first time, we have demonstrated that these mitochondrial formylated peptides are present and elevated in ARDS and that they directly drive lung inflammation. This, therefore, highlights a potential novel therapeutic target for this life threatening illness.'' says Professor Adriano Rossi, MRC Centre for Inflammation Research, University of Edinburgh

ARDS typically affects patients, who are already critically ill and can be triggered by severe injuries or infections such as pneumonia. Mitochondrial formylated peptides are released from the body’s cells when they die.

Therapies, that target these molecules, could potentially help patients with any type of ARDS, whether caused by an infection or not, the researchers say.

The study is published in the journal Thorax. It was funded by the Wellcome Trust and the Medical Research Council. ω.

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Folic Acid Found to Enhance Children’s Psychological Development

Image: Ulster University

 

|| May 07: 2017: Ulster University News || ά. Ulster University scientists have discovered that taking folic acid supplements throughout pregnancy enhances psychological development in children. Folic acid, taken during the first three months of pregnancy, can prevent neural tube defects such as spina bifida, that occurs when the fetus’ spine and back do not close during development. It is, also, known that taking folic acid in the first trimester of pregnancy can have beneficial effects on children’s brain development but until now it was not known if continued supplementation throughout pregnancy had any additional effects.

Ulster University’s researchers investigated whether continued supplementation throughout pregnancy had any additional effects. They asked the parents of 39 children, now aged seven, to answer questions about their child’s personality, including levels of resilience, relationships with others and how they express their emotions. Within this group 22 mothers had taken the supplement throughout their pregnancy while the other 19 took it during the first three months only. The results showed that children, whose mothers took the supplement throughout pregnancy demonstrated higher levels of emotional intelligence and resilience.

Further analysis, further, showed that the level of folic acid in the mother’s blood towards the end of pregnancy was a good predictor of children’s resilience and emotional intelligence.

Ulster University’s research was part of an ongoing study, which started 10 years ago with a trial of folic acid during pregnancy, and which, to date has been funded to the value of £890,000 in awards from the Health and Social Care RD Office Enabling Award and a ESRC BBSRC interdisciplinary scheme and with the support of five fully-funded PhD studentships from DEL NI.

Ulster University’s Professor Tony Cassidy said, “Most expectant mothers know that taking folic acid supplements in the first three months of pregnancy is important for the baby’s spinal development. Our study shows that there are additional psychological benefits for the child if supplements are taken throughout pregnancy.

This presents a number of opportunities for further research and to, also, further explore government recommendations for women to take folic acid for the duration of pregnancy rather than stopping at the end of the first trimester.” ω.

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General Transcription Factors Used Specifically for Regulating Lipid Metabolism

Image: University of Chinese Academy of Sciences



|| April 30: 2017: University of Chinese Academy of Sciences News || ά. Lipid is the major form of energy storage in organisms. Disorders of lipid storage and lipid metabolism lead to many severe human diseases, such as obesity, fatty liver and diabetes. Lipid droplets:LDs are main lipid storage structures in most cells. The size of LDs is closely related to different cellular functions or metabolic status. Previous studies have identified numerous regulatory mechanisms of lipid storage and LD dynamics.

However, our understanding of the lipid storage network and regulation of LD dynamics is far from clear. The recent study in Professor Xun Huang’s lab from Institute of Genetics and Developmental Biology of Chinese Academy of Sciences identified that general transcription factors, including TRF2 and TAF9, regulate LD size and phospholipid fatty acid composition in Drosophila larval fat body.

Inactivation of trf2 and taf9 results in larger LDs and increased level of fatty acids with long chain lengths in phospholipids. We found that TRF2 and TAF9 affect these biological processes by modulating the transcription of a common set of genes, including peroxisomal fatty acid oxidation-related genes and other genes such as eIF2B.

Our findings, therefore, reveal that general transcription factors, which were previously thought to be involved in the transcription of all genes, can play a specific role in lipid homeostasis. The research was published on PLoS Genetics. ω.

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What are You Doing: I'm Giving Morphine to the Fish

Image: University of Liverpool

 

|| April 27: 2017: University of Liverpool News || ά. Having previously debunked the fisherman’s legend that fish don’t feel pain, the University of Liverpool’s Dr Lynne Sneddon has become a leading figure in the movement to reduce, replace and refine the use of animals in scientific research. Uncomfortable with the increasing use of adult fish in pain research, Dr Sneddon and colleague Dr Javier Lopez-Luna at the Institute of Integrative Biology, have led a new study to investigate a potential alternative.

“Previous studies have identified multiple subtypes of pain receptors in zebrafish, even as early as a few days post-fertilisation.” the researchers note. Could they replace the adult fish, that are used in research with larvae, that are a matter of days old? Only if they could prove that the larvae respond to pain and any discomfort could be relieved. The study, which is published in the Journal of Experimental Biology, involved exposing five-day-post-fertilisation zebrafish embryos to dilute concentrations of acetic acid and citric acid.

Theses acids are known to irritate adult fish. The researchers then track the larvae’s activity with software, produced by researchers from the University’s Department of Electrical Engineering and Electronics.

Analysing the minute fish’s motion, they noticed that the larvae became less active in the two most dilute concentrations of acetic acid, 0.01 and 0.1%. However, the most concentrated acetic acid, 0.25% and all three concentrations of citric acid, 0.1, 01 and 05%, stimulated the fish to swim harder and farther, possibly in a bid to escape the uncomfortable sensation.

But when the team administered pain relief to the disturbed fish larvae, in the form of aspirin, morphine and lidocaine, their discomfort appeared to be relieved and their behaviour returned to normal.

Now, having confirmed that larval fish are capable of experiencing pain and benefit from pain relief, the researchers recommend that larval zebrafish can be used as a model for the study of pain and pain receptors, sparing many of the adult fish that are currently used in toxicity tests.
ω.

The Paper: ‘Reduction in activity by noxious chemical stimulation is ameliorated by immersion in analgesic drugs in zebrafish’ is published in the Journal of Experimental Biology: DOI: 10.1242/jeb.146969

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Nanotubes That Assemble Themselves: A Piece of Research Shows That Has Taken Twenty Years of Human Perseverance, Dedication and Determination to Carry on with the Task

 

|| April 25: 2017: Lund University Sweden News || ά. Researchers from Lund University in Sweden have succeeded in producing nanotubes from a single building block, using so-called molecular self-recognition. The tube can, also, change shape depending on the surrounding environment. The results can contribute to the future development of transport channels for drugs through the cell membrane. In the present study, researchers from Lund University in Sweden, together with colleagues from Vilnius University in Lithuania, have studied how molecules attach to each other, using weak chemical bonds to form large structures.

The aim of the study was to determine the smallest possible size of these molecules, in which, they are still able to provide enough information to successfully attach and form a desired large structure. The researchers’ strategy has been to use many weak hydrogen bonds, which assemble themselves in a pre-programmed manner. “It took 20 years for us to discover the design of this molecule, which resulted in molecular nanotubes.” says Professor Kenneth Wärnmark, chemistry professor at the Faculty of Science at Lund University.

As a unique bonus, they, further, discovered that the molecule can construct different shapes, depending on its environment. The researchers are able to modify this environment, partly, through their choice of solvent and, partly, through their choice of a so-called 'guest molecule'. “The molecules can form a tube, but also, change into the shape of a capsule or a molecular belt.'' says Professor Kenneth Wärnmark.

Unlike the developed carbon nanotubes, which are already on the market, the new molecular nanotubes can be regulated with regard to the diameter. Furthermore, the manufacturing process is both simpler and more environmentally friendly compared to that of the carbon nanotubes, which are made from individual carbon atoms and are assembled using strong chemical bonds at high temperature.

“Being able to regulate the diameter is importance if you, for instance, want to use the tubes to transport something inside” says Professor Kenneth Wärnmark.

One possible application is the transport of drugs through a cell membrane for which the molecular nanotube can serve as a channel. The diameter of the tube and the properties of its surface make it suitable for transporting substances, that regulate nerve signals in the human body, such as acetylcholine.

“People with Alzheimer’s disease suffer from acetylcholine deficiency and hopefully, in the future, this could be a way to reduce the impact of the disease. However, it requires a lot more research as well as clinical studies before we know whether or not it works.” says Professor Kenneth Wärnmark.

The Paper: Stimuli-controlled self-assembly of diverse tubular aggregates from one single small monomer

Contact: Professor Kenneth Wärnmark: Department of Chemistry, Lund University: +46 46 222 82 17: kenneth.warnmark at chem.lu.se: ω.

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Study Explores How Bacteria Survive Human Immune System

Image: Queen's University Belfast

|| March 23: 2017: University of East Anglia News || ά. Researchers have uncovered molecular details of how pathogenic bacteria fight back against the human immune response to infection. Scientists at the University of East Anglia and Institut de Biologie Structurale:CEA-CNRS-UGA, France, have identified the structure of NsrR, a bacterial protein, that binds to DNA and plays a key role in the bacterium’s resistance to nitric oxide:NO, which is produced in the initial immune response to infection.

In order to counter the effects of NO, which can be toxic to living organisms, many bacteria have evolved ways to detect it and mount a cellular response. The most common, dedicated NO sensor in bacteria is the regulatory protein NsrR. Regulatory proteins bind to DNA and in doing so control whether particular genes are switched on or off. NsrR contains a specialised type of co-factor, an additional component of a protein needed for its activity, called, an iron-sulfur cluster.

These are very fragile and reactive, which makes them hard to work with but recent work in the Schools of Chemistry and Biology at UEA have provided important new information on how NsrR functions as a sensor of NO. The team has now identified structures of the protein in its two principal forms, cluster-free and cluster-bound, showing key differences, that demonstrate how NsrR responds to NO.

These structural changes show how NsrR switches between DNA-binding and non-binding forms, enabling it to regulate the switching on or off of the production of enzymes, which combat NO.

Professor Nick Le Brun, professor of Biological Chemistry, led the work at UEA. Professor Le Brun said, “NsrR belongs to an important but poorly understood family of regulators, members of which, are involved in a wide range of essential cellular functions in bacteria.

Many of these regulators have been shown or are predicted to contain an iron-sulfur cluster but our work provides the first example of a structure with the fragile cluster bound. It reveals the general mechanism, by which, these regulators respond to different signals.

Furthermore, the structure reveals that the cluster is co-ordinated to the protein in a way that has not been observed before in biology. The process of how pathogens survive human immune responses is complex and every step we take towards understanding it, the greater the possibility of developing intervention strategies, that disable the response.”

‘Crystal structures of the NO sensor NsrR reveal how its iron-sulfur cluster modulates DNA binding’, is published in the journal Nature Communications.
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Amino Acids in Diet Could Be Key to Starving Cancer

Chemotherapy: Image: University of Adelaide

 

|| March 21: 2017: University of Glasgow News || ά. Cutting out certain amino acids, the building blocks of proteins, from the diet of mice slows tumour growth and prolongs survival, according to new research published in Nature. Researchers at the Cancer Research UK Beatson Institute and the University of Glasgow found that removing two non-essential amino acids, serine and glycine, from the diet of mice slowed the development of lymphoma and intestinal cancer. The researchers found that the special diet made some cancer cells more susceptible to chemicals in cells, called, reactive oxygen species.

Chemotherapy and radiotherapy boost levels of these chemicals in the cells, so this research suggests that a specially formulated diet could make conventional cancer treatments more effective. The next stage would be to set up clinical trials with cancer patients to assess the feasibility and safety of such a treatment. Dr Oliver Maddocks, a Cancer Research UK Scientist at the University of Glasgow, said, “Our findings suggest that restricting specific amino acids through a controlled diet plan could be an additional part of treatment for some cancer patients in future, helping to make other treatments more effective.

Professor Karen Vousden, Cancer Research UK’s Chief Scientist and the study Co-author, said, “This kind of restricted diet would be a short term measure and must be carefully controlled and monitored by doctors for safety. Our diet is complex and protein, the main source of all amino acids, is vital for our health and well-being. This means that patients cannot safely cut out these specific amino acids, simply by following some form of home-made diet.”

Amino acids are the building blocks, that cells need to make proteins. While healthy cells are able to make sufficient serine and glycine, cancer cells are much more dependent on getting these vital amino acids from the diet.

However, the study, further, found that the diet was less effective in tumours with an activated Kras gene, such as most pancreatic cancer, because the faulty gene boosted the ability of the cancer cells to make their own serine and glycine. This could help to select which tumours could be best targeted by diet therapy.

Dr Emma Smith, Science Communication Manager at Cancer Research UK, said, “This is a really interesting look at how cutting off the supply of nutrients essential to cancer cell growth and division could help restrain tumours.

The next steps are clinical trials in people to see if giving a specialised diet that lacks these amino acids is safe and helps slow tumour growth as seen in mice. We’d, also, need to work out which patients are most likely to benefit, depending on the characteristics of their cancer.” ω.

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Scientists Find Celastrol Can Play Drug's Role in Weight Loss

Tripterygium Regelii, Thunder-god-vine, Aizu area, Fukushima, Japan. Image: Public Domain

 

|| April 18: 2017: Chinese Academy of Sciences News || ά.  Chinese scientists have identified the chemical mechanism of celastrol, which they call, one of the most potent natural weight-loss agents, marking another step toward its possible future development into a major weight-loss drug. The compound is extracted from the roots of thunder god vine, a toxic herb, has been in use in traditional Chinese medicine for centuries to cure arthritis and autoimmune diseases. In TCM, however, it is used in tiny amounts, mainly to treat severe diseases, because of its potentially dangerous side effects.

A research team, led by Zhang Xiaokun, President of Xiamen University's Institute for Biomedical Research, found celastrol can change a cell's metabolism by eliminating inflamed mitochondria, leading to weight loss. Mitochondria are the cell's 'energy factory'. "This is a huge step in turning celastrol into a feasible and safe medicine for humans." he said. "Celastrol could be a powerful tool to treat patients, suffering from obesity and associated complications, such as Type two diabetes, heart disease and fatty liver."

Celastrol has long been a hot subject in biomedicine. In 2007, Cell, a science journal, listed celastrol with the discovery of antimalarial drug artemisinin, which won chemist Tu Youyou the Nobel Prize in 2015, among five natural herbal compounds with the most potential for modern medicine. In 2015, scientists at Boston Children's Hospital and Harvard Medical School discovered celastrol could help obese mice lose up to 45 percent of their body fat by enhancing a cell's reaction to an appetite-suppressing hormone called leptin.

However, scientists did not know exactly how celastrol affects a cell's bioactivities. ''Since celastrol and the plant it comes from are extremely toxic, 'some people were very skeptical or even objected to the idea that people can eat such a thing.'' Zhang said. "After all, the vine has a scary, centuries-old nickname: gut-cutting grass.

Terrifying as it may sound, on a cellular level, 'celastrol, may be, beneficial because it acts on an orphan receptor, called, Nur77, which induces inflamed mitochondria to dissolve, effectively taking out the root cause of many chronic inflammation diseases, such as obesity, tumours and metabolic diseases.'

Mitochondria play a key role in cellular death, immunity and inflammation. By killing the malfunctioning mitochondria, celastrol can help control cell metabolism and increase a cell's sensitivity to leptin, a hormone, that inhibits hunger, thus, leading to weight loss.''

Zhang said that his team, whose findings were published this month by Molecular Cell, an international science journal, would now focus on how celastrol regulates metabolism in greater detail and find ways to reduce the substance's toxicity while keeping its weight loss potency.

Also, scientists are looking for other receptors for celastrol, that, may, affect cells differently and possibly offer new solutions to chronic metabolic or autoimmune diseases, such as rheumatoid arthritis, tumours and AIDS. ω.

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Sodium Citrate Spray Could Temporarily Restore the Sense of Smell

Image: University of East Anglia

|| April 15: 2017: University of East Anglia News || ά. A substance, commonly used to treat bladder issues, could temporarily treat people, who have lost their sense of smell, according to research published in the journal Clinical Otolaryngology. A study by the University of East Anglia with the Smell and Taste clinic at the James Paget University Hospital showed sodium citrate nasal spray could offer temporary improvement in the ability to smell for patients suffering from anosmia or hyposmia, the loss of smell, in cases, caused by a virus or other non-obstructive causes.

Sodium citrate, the sodium salt of citric acid, is safe to use and already licensed for medicinal uses in the stomach and bladder. Sodium citrate is known to bind calcium. Calcium molecules are key in cell function and are believed to be involved in ‘turning down’ the sense of smell. Researchers wanted to investigate if reducing calcium in the mucus in the nose would suppress its ability to inhibit a person’s sense of smell. Mr Carl Philpott from the University, said, “The sodium citrate nasal spray was designed to ‘mop up’ calcium molecules in nasal mucus and as a result, temporarily turn up the sense of smell.

In the randomised trial, patients were treated either with sodium citrate spray or sterile water. They were then invited to take part in a series of tests, smelling increasingly stronger concentrations of four different odours, roses, pear, vinegar and menthol, noting at what concentration they could detect the smell.

Results showed an improvement in those treated with the spray, which lasted for up to two hours. It seemed to be most effective in people whose ability to smell was damaged by viral infection, called post viral olfactory loss or PVOL.”

The loss of smell can have a significant impact on sufferers. It can often lead to reduced intake of nutritional food and weight loss as well as affecting personal relationships, social enjoyment and having a negative impact on psychological wellbeing. Of the patients randomised to be treated with sodium citrate spray, one third showed an improvement with the peak effect seen between 15 and 30 minutes after treatment. Minor side effects noted by patients included a sore throat, slightly runny nose and itching.

Mr Philpott said, “This study offers proof of concept that sodium citrate spray, may, enhance a damaged sense of smell in patients with partial loss of smell not caused by obstructions.

Further study in the form of larger clinical trials with patients applying the treatment regularly would help inform whether this treatment should be offered routinely by doctors. It could quite easily and safely be formulated into a treatment to provide temporary relief from smell loss, enhancing the quality of life of patients with very few side effects.”

The research was done in UK by a team led by Mr Carl Philpott at James Paget University Hospital and mirrors work done in Germany by Professor Thomas Hummel at the Dresden Smell and Taste Clinic. ω.

The Paper: ‘A randomised controlled trial of sodium citrate spray for non-conductive olfactory disorders’ is published in the journal Clinical Otolaryngology, DOI: 10.1111/coa.12878

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New Breed of Supermolecule That Hunts Down Harmful Drugs and Removes Them From Water

Images: University of Exeter

 

|| April 15: 2017: University of Surrey News || ά. The University of Surrey researchers have discovered a 'supermolecule', that can be used to 'de-chemicalise', drug-contaminated water. The research involves the detection and removal of pharmaceuticals from water, as contamination from pharmaceuticals can enter the aquatic environment as a result of their use for the treatment of humans and animals. This contamination can be excreted unchanged, as metabolites, as unused discharge or by drug manufacturers.

The research has found that a new type of ‘supermolecule’, calix4, actively seeks certain pharmaceuticals and removes them from water. Contamination of water is a serious concern for environmental scientists around the world, as substances include hormones from the contraceptive pill and pesticides and herbicides from allotments. Contamination can, also, include toxic metals, such as mercury, arsenic or cadmium, which was previously used in paint or substances, that endanger vital species, such as bees.

Professor Danil de Namor, University of Surrey Emeritus Professor and Leader of the research, said, “Preliminary extraction data are encouraging as far as the use of this receptor for the selective removal of these drugs from water and the possibility of constructing a calix4-based sensing devices.

From here, we can design receptors so that they can bind selectively with pollutants in the water so the pollutants can be effectively removed. This research will allow us to know exactly what is in the water and from here it will be tested in industrial water supplies, so there will be cleaner water for everyone. The research, also, creates the possibility of using these materials for on-site monitoring of water, without having to transport samples to the laboratory.”

Dr Brendan Howlin, University of Surrey Co-investigator, said, “This study allows us to visualise the specific receptor-drug interactions leading to the selective behaviour of the receptor. As well as the health benefits of this research, molecular simulation is a powerful technique, that is applicable to a wide range of materials.

We were very proud that the work was carried out with PhD students and a final year project student and research activities are already taking place with the Department of Chemical and Processing Engineering:CPI and the Advanced Technology Institute:ATI.

We are, also, very pleased to see that as soon as the paper was published online by the European Journal of Pharmaceutical Sciences, we received invitations to give keynote lectures at two international conferences on pharmaceuticals in Europe later this year." ω.

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And This is How the Superbugs Develop Their Power of Resistance

Image: University of Central Lancashire


|| April 11: 2017: University of Central Lancashire News || ά. Researchers have discovered how some superbugs, including MRSA, meningitis and pneumonia, can become resistant to one of the key antibiotics of last resort, marking a significant leap forward in the global fight against antibiotic resistance. The study, published today,  April 11, in Nature’s Scientific Reports, has shown that a specific protein, known as VanS, binds with Vancomycin, one of the antibiotics of last resort.

This discovery offers crucial new insight into the mechanisms, involved in activating resistance genes in some of the most difficult-to-treat and deadly infections, including penicillin-resistant pneumonia and MRSA, one of the most serious hospital-acquired infections. This breakthrough discovery was found by researchers at the University of Central Lancashire and the University of Nottingham. Antibiotics of last resort are used to tackle serious and multi-drug-resistant infections when other potential treatments have failed.

Since some bacterial strains are now, also, evolving to become resistant to this last line of defence, fundamental research, which addresses how this antibiotic resistance is triggered is crucial to address this global issue. It is estimated that antimicrobial resistance, which renders existing antibiotics useless against some bacterial infections, will lead to the loss of 10 million lives a year by 2050 and cost £69tn per year globally. This is according to the Review on Antimicrobial Resistance published in 2016*, which highlights the severity of the issue.

Dr Mary Phillips-Jones, Director of the study and Senior Lecturer in Biochemistry and Microbiology at the University, said: “We’ve identified that the important antibiotic, known as Vancomycin, binds directly to a specific protein in the membrane of some key bacteria. We believe this may then trigger the resistance mechanism, most likely in combination with other additional factors.

Understanding how these ‘resistance triggering’ mechanisms work in bacteria means that we can find new ways of destroying them, taking us one step closer towards combating these harmful superbugs.”

Stephen Harding, Co-director of the study and Professor of Applied Biochemistry at the University of Nottingham, said, “Many bacteria are very clever in quickly adapting to defend against the medicines, used to kill them. Identifying the key interaction point is a major step in helping us to permanently outwit them.”

The work was carried out at the University of Central Lancashire and the University of Nottingham and also, utilised facilities made available at the University of Leeds and the Diamond Light Source Ltd, Oxfordshire. The study was supported financially by the University of Central Lancashire’s School of Pharmacy and Biomedical Sciences and the National Centre for Macromolecular Hydrodynamics at the University of Nottingham. ω.

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Chemotherapy is Probably One of the Most Cruellest Kind of Treatments That a Human Physiology Could Be Subjected to But Those Who Must Go Through with It Go for They Must: But Just Watching Them Going Through with It is Huge Enough a Cause for Others to Run Away From Medicine: And Therefore, If Any Advance Towards Minimising These Horrendous Side Effects is Achieved It is a Beautiful News: Which a PhD Student Hannah Wardill Has to Declare

Image: University of Adelaide

 

|| April 09: 2017: University of Adelaide News || ά. Researchers at the University of Adelaide, may have, uncovered the secret to making life-saving chemotherapy significantly less uncomfortable for cancer patients everywhere. Being diagnosed with cancer, one of the world’s most enduring and undiscriminating killers, is distressing enough. But making it a doubly cruel blow is the fact that undergoing one of its most effective treatments, chemotherapy, can itself be utterly debilitating and even life threatening. And people, who have not seen others going through the treatment of chemotherapy do not really any any concept of how desperately horrendous an experience it is for a human physiology to be made helplessly subjected to.

Worldwide, anywhere from 60-80% of patients treated, depending on the dosage and type of chemotherapy used, experience discomforting side-effects. such as diarrhoea, heightened pain sensitivity and, in some cases, sepsis, a potentially fatal immune system response. Because of the efforts of researchers at the University of Adelaide’s School of Medical Sciences, however, those numbers appear set to drastically improve. Led by PhD student and Channel Nine Young Achiever Award winner for 2016 in Science and Technology Hannah Wardill, the team has identified a single immune receptor as the likely common trigger for two major sources of chemo-related symptoms.

“Our research has focused on the immune receptor, known as Toll-Like receptor four:TLR4, which has been implicated not only in the development of gastrointestinal symptoms but also appears to control people’s sensitivity to pain.”says Ms Wardill

According to Ms Wardill, TLR4 sets up an inflammatory response in the gut that is exacerbated by chemotherapy. “By knocking out the TLR4 receptor in our test animals, we saw improvements across all key markers of gut toxicity, as well as signs of reduced pain. This is the first time a tangible link has been identified between gastrointestinal and neurological toxicity following chemotherapy, and further highlights the communication that exists between the brain and the gut.”

Greatly encouraged by these findings, first published in 2015 in the respected journal Cancer Treatment Reviews, Ms Wardill’s team has now turned its attention to finding ways to safely inhibit TLR4 in human patients. “We’ve harvested representative intestinal cells and are now testing methods of pharmacologically inhibiting TLR4 in the gut only,” she says. “This specificity of location is very important, because other research has shown that some TLR4 is required in the body in order for chemotherapy to effectively target tumour cells.”

A particularly exciting aspect of this research, adds Ms Wardill, is the potential to not only improve quality of life for cancer patients during chemotherapy treatment, but to indirectly increase the effectiveness of all cancer treatment.

“If we could help patients avoid experiencing diarrhoea and heightened pain as side-effects of chemotherapy, they would consequently avoid the multiple, co-existing health problems that so often arise as a result, allowing oncologists to treat them more effectively.It would be a fantastic step forward for millions of people all over the world.”
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How Did You Get to the Skeletons: Well, When Chemistry Changes the Biochemistry of Life One Must Follow the Resulting Laws

New species of gastropod snail Phymorhynchus n. sp. Image: David Shale: University of Southampton

 

|| April 05: 2017: University of Edinburgh News || ά. Skeletons and shells first came into being 550 million years ago as the chemical make-up of seawater changed, a study suggests. Ancient marine life may have developed from soft-bodied animals into creatures with hard body parts as oxygen levels rose and calcium and magnesium levels in prehistoric oceans changed, researchers say. Until now, little was known about how skeletons and shells, which are made of calcium carbonate, first evolved, the team says.

Previous theories suggested that soft-bodied organisms had undergone a mass extinction, which allowed organisms with skeletons and shells to flourish. However, Edinburgh researchers have found that the earliest lifeforms with hard body parts co-existed with closely related soft-bodied species. The team examined a range of fossils unearthed from limestone rocks in Siberia, which formed millions of years ago from seawater with high levels of calcium carbonate.

They concluded that hard-bodied lifeforms were first present only in such environments, where high levels of calcium carbonate allowed organisms to develop primitive hard parts. Around 10m years later, the diversity of life of Earth increased rapidly, a period, known as the Cambrian explosion and hard-bodied life began to thrive.

An increased threat from predators led lifeforms to develop new, more complex hard parts in environments, that were less carbonate-rich, the team says. The development of hard body parts, through a process, called, biomineralisation, marked a significant evolutionary advance from the previous world of soft-bodied life, the team says.

The study is published in the journal Proceedings of the Royal Society B. The research was carried out in collaboration with Lomonosov Moscow State University.

'' How animals produced shells and skeletons is one of the major events in the evolution of life. We are only now starting to understand the processes underlying this revolution.'' said Professor Rachel Wood, from the School of GeoSciences.
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A New Way to See the Biological Processes at Work in Proteins

Prediction map with probability contours showing clustering of tail-anchored membrane proteins to different organelle
locations based on hydrophobicity and tail charge. Peroxisomes, green; mitochondria, blue; endoplasmic reticulum,
red. Images: University of Exeter

 

|| April 04: 2017: University of East Anglia News || ά. A team of scientists at the University of East Anglia:UEA has developed a novel way to obtain previously inaccessible insight into the functions of a group of essential proteins. Many proteins contain a co-factor, an additional component, that is often crucial for the protein’s function. Iron-sulfur clusters are protein co-factors, that play essential roles in a wide range of processes, including respiration, photosynthesis and DNA replication or repair.

Additionally, iron-sulfur cluster proteins play key roles in sensing environmental change, enabling bacteria to mount an adaptive response. This is crucial for their survival, for example, in pathogens, trying to evade the human immune system. Iron-sulfur clusters are reactive and fragile, making them difficult to work with and their functional properties are often complex. UEA researchers have developed a new method to study these delicate iron-sulfur clusters, based on mass spectrometry, an advanced technique, that can identify proteins by measuring their mass with great accuracy.

In common life science applications of mass spectrometry, the proteins, being studied, are in an unfolded state and any information on co-factors is lost. The team has developed ways to keep iron-sulfur cluster proteins in a folded state with the cluster bound during the mass spectrometry experiment and to monitor their reactivity in real time.

FNR is an iron-sulfur cluster-containing protein, which functions as an oxygen:O2, sensor. It is key for the ability of bacteria such as E. coli to ‘breathe’ in the absence of O2 and it undergoes a complex cluster conversion process when O2 is present. This abolishes its ability to bind DNA, enabling it to regulate the switching on of enzymes, which utilise O2 for respiration and to switch off those, that can’t.

Using their mass spectrometry approach, the researchers were able to detect for the first time all of the reaction components simultaneously, providing unprecedented details of the conversion process.

Professor Nick Le Brun from UEA’s School of Chemistry, who led the team, said, “This work demonstrates the exciting potential of mass spectrometry to provide a level of insight into this common cofactor that was previously not possible.

The ability to ‘see’ and clearly distinguish all reacting species in this process at the same time is hugely advantageous. Given the importance and ubiquitous nature of iron-sulfur cluster proteins, the methodology we have developed promises to have widespread application across further research into systems involving interactions and reactions of protein cofactors, particularly with small molecules like O2, nitric oxide, nitrogen and hydrogen.”

The study was funded by the Biotechnology and Biosciences Research Council:BBSRC.
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The Paper: ‘Mass spectrometric identification of intermediates in the O2 driven 4Fe-4S to 2Fe-2S cluster conversion in FNR’ is published in the journal Proceedings of the National Academy of the USA – DOI: 10.1073/pnas.1620987114

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Scientists Find Conserved Features in Zika Virus NS5 Structure That Will Accelerate Drug Development

Image: University of Chinese Academy of Sciences  

 

|| April 02: 2017: University of Chinese Academy of Sciences News: Shi Yi Writing || ά. The Zika virus nonstructural protein Five-NS5 is the largest enzyme and the most conserved protein of the virus and plays a critical role in viral replication. NS5 carries two essential enzymatic activities, methyltransferase:MTase and RNA-dependent RNA polymerase:RdRp, which are both promising targets for the development of antiviral compounds.

Recently Professor George F. Gao and Professor Yi Shi from University of Chinese Academy of Sciences in Beijing and their colleagues solved the crystal structures of NS5 MTase. NS5 MTase is a complex with an RNA cap analogue:m7GpppA and the free NS5 RdRp from the ZIKV involved in the 2015 outbreak in Brazil. The article entitled, 'The crystal structure of Zika virus NS5 reveals conserved drug targets' was published in The EMBO Journal recently. For the MTase, the GTP‐binding and SAM‐binding pockets are potential targets for antiviral development.

The RNA template entry tunnel and the 'N pocket', close to the enzyme active site are promising inhibitor binding sites. The authors identified the conserved features of ZIKV NS5 MTase and RdRp structures that could lead to development of current antiviral inhibitors against flaviviruses, including dengue virus and West Nile virus, to treat ZIKV infection.

Their results could inform and accelerate the structure-based design of antiviral compounds against ZIKV. This work was supported by the Emergency Task-Force Project of the National Natural Science Foundation of China:NSFC, the Excellent Young Scientist Program from the NSFC and the NSFC Innovative Research Group.

This work is, also, supported by the China Ministry of Science and Technology National 973 Project, the Task-Force of Zika Virus Research from the Chinese Academy of Sciences:CAS, the National Key Plan for Scientific Research and Development of China, Zika Special Project of the Ministry of Science and Technology Reform and Development Project and Strategic Priority Research Program of CAS, the External Cooperation Program of CAS, the Excellent Young Scientist Program of CAS and the Youth Innovation Promotion Association CAS. ω.

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Nanoparticle Paves the Way for New Triple Negative Breast Cancer Drug

Image: Queen's University Belfast


|| April 01: 2017: Queen's University Belfast News || ά.  A potential new drug to tackle the highly aggressive ‘triple negative’ breast cancer and a nanoparticle to deliver it directly into the cancer cells, has been developed by researchers. The research, a collaborative project between Queen’s University Belfast and Ulster University, began at the Queen’s Centre for Cancer Research and Cell Biology:CCRCB in 2014 and was led by Professor Mohamed El-Tanani.

Professor El-Tanani discovered the peptide drug, which blocks a protein, known as RAN. High levels of RAN have been linked to aggressive tumour growth, cancer spread, resistance to chemotherapy and poor prognosis in a number of cancers, including triple negative breast cancer:TNBC. The team, which, also, includes the University of Bradford, where Professor El-Tanani is now based, has developed a nanoparticle to help deliver the drug directly into cancer cells.

Laboratory tests showed that when this nanoparticle, loaded with the peptide, was added to the triple negative breast cancer cells, the cells would actively take it in. Their growth rate was then reduced and around two thirds of the cells died within 24 hours. This compared with the peptide on its own or an empty nanoparticle, which had no impact on the cells’ growth.

Dr Kyle Matchett from Queen’s CCRCB, and an Author in the study, said, “The peptide prevents RAN from being activated but in its normal form it degrades quickly, reducing its effectiveness. This novel delivery mechanism of using a small capsule, known as a nanoparticle, allows the drug to directly target the cancer cells and increases its effect.

The research is potentially life-saving. We are one step closer to a new treatment and we will now do further pre-clinical experiments in the laboratory prior to the clinical trials stage.”

The research was recently published in the International Journal of Pharmaceutics. ω.

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Weather Forecasting Technology Used to Predict Where Proteins Anchor Inside Human Cells

Prediction map with probability contours showing clustering of tail-anchored membrane proteins to different organelle
locations based on hydrophobicity and tail charge. Peroxisomes, green; mitochondria, blue; endoplasmic reticulum,
red. Images: University of Exeter

 

|| March 30: 2017: University of Exeter News || ά. Met Office technology used to study climate change is being used by scientists to predict the sorting and location of proteins in cells of the human body. Proteins are large biomolecules, which are required for the structure, function and regulation of the cells in the human body. After their production, many proteins have to be routed to specific locations inside the cell for it to work properly. Researchers at the University of Exeter have made a key finding about the signals and mechanisms, which mediate and regulate this protein sorting in the cell.

They have discovered how an important group of membrane proteins, which function as adaptor molecules at the surface of cellular compartments, are routed to their specific target membranes. Proper targeting of these membrane adaptors is crucial for the function of cellular compartments. Mis-targeting or loss of adaptor function leads to a range of severe or fatal disorders associated with metabolic, developmental or neurological defects. Dr Michael Schrader, from the University, who led the study, said, “This research has allowed us to better understand how the cell sorts and delivers these proteins.

We now know which properties determine how they travel to specific organelles and can exploit this knowledge to predict the localisation of hitherto uncharacterised adaptor proteins encoded in the human genome.” The study has identified for the first time the specific chemical properties in tail-anchored membrane proteins which determine where they travel in a cell.

It reveals that a combination of tail charge and hydrophobicity or water-fearing of the membrane-spanning domain determines targeting to distinct organelles. Subtle alterations in those physicochemical parameters are sufficient to shift adaptor protein targeting between organelles. Dr Schrader said, “Our findings can be used to modulate and improve targeting of membrane adaptors. This could also improve medical treatment, because researchers could use this information to produce drugs which better target specific organelles.”

The researchers are working with experts from the Met Office. "It can be expensive and slow to run the most accurate computer simulations of the Earth's climate, so we are always looking for ways to make the best use of the data we have. It turns out the statistical methods we use to predict climate change are useful for predicting where proteins anchor within the cell." said Co-author Doug McNeall from the Met Office.

The University of Exeter’s research, funded by BBSRC, was carried out in cooperation with the University of Heidelberg:Mannheim, the EMBL Hamburg and the National University of Singapore.The paper, Predicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells, is published in the Journal of Cell Science.

The authors were Joseph Costello, Inês Castro, Fátima Camões, Tina A. Schrader, Doug McNeall, Jing Yang, Evdokia-Anastasia Giannopoulou, Sílvia Gomes, Vivian Pogenberg, Nina A Bonekamp, Daniela Ribeiro, Matthias Wilmanns, Gregory Jedd, Markus slinger and Michael Schrader. ω.

The Paper: 'An immortalised adult human erythroid line facilitates sustainable and scalable generation of functional red cells' by Jan Frayne et al in Nature Communications.

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The University of Bristol Gives the World and Humanity: BEL-A's Blood

 

|| March 27: 2017: University of Bristol News || ά. Researchers have generated the first immortalised cell lines, which allow more efficient manufacture of red blood cells. The team, from the University of Bristol and NHS Blood and Transplant, were able to manufacture red blood cells in a more efficient scale than was previously possible. The results, published in Nature Communications, could, if successfully tested in clinical trials, eventually lead to a safe source of transfusions for people with rare blood types and in areas of the world, where blood supplies are inadequate or unsafe.

Previously, research in this field focused on growing donated stem cells straight into mature red blood cells. However, that method presently produces small numbers of mature cells and requires repeat donations. The world-leading team in Bristol have now developed a robust and reproducible technique, which allows the production of immortalised erythroid cell lines from adult stem cells. These premature red cells can be cultured indefinitely, allowing larger-scale production, before being differentiated into mature red blood cells.

Dr Jan Frayne, from the University of Bristol’s School of Biochemistry, said, “Previous approaches to producing red blood cells have relied on various sources of stem cells, which can only presently produce very limited quantities. By taking an alternative approach we have generated the first human immortalised adult erythroid line, Bristol Erythroid Line Adult or BEL-A, and in doing so, have demonstrated a feasible way to sustainably manufacture red cells for clinical use from in vitro culture.

“Globally, there is a need for an alternative red cell product. Cultured red blood cells have advantages over donor blood, such as reduced risk of infectious disease transmission.” Professor Dave Anstee, Director at the NIHR Blood and Transplant Research Unit in Red Cell Products, which is a collaboration between the University of Bristol and NHS Blood and Transplant, said, “Scientists have been working for years on how to manufacture red blood cells to offer an alternative to donated blood to treat patients.

The first therapeutic use of a cultured red cell product is likely to be for patients with rare blood groups because suitable conventional red blood cell donations can be difficult to source. The patients who stand to potentially benefit most are those with complex and life-limiting conditions like sickle cell disease and thalassemia, which can require multiple transfusions of well-matched blood. The intention is not to replace blood donation but provide specialist treatment for specific patient groups.”

The cells were cultured at the University of Bristol and at NHS Blood and Transplant’s Filton site. NHS Blood and Transplant needs to collect 1.5 million units of blood each year to meet the needs of patients across England and the ongoing need for life saving blood donations remains. It would be many years before manufactured cells could be available on a large scale.

NHS Blood and Transplant announced plans for in-man trials of manufactured blood in 2015. This first trial will not use Bel-A cells. The first trial, due to start by the end of 2017, will use manufactured red cells from stem cells in a normal blood donation.

The research was funded by The Department of Health, The Wellcome Trust, NHS Blood and Transplant, BrisSynBio via a BBSRC:EPSRC Synthetic Biology Research Centre Grant, National Institute for Health Research Blood and Transplant Unit (NIHR BTRU) in Red Blood Cell Products at the University of Bristol in Partnership with NHS Blood and Transplant:NHSBT.
ω.

The Paper: 'An immortalised adult human erythroid line facilitates sustainable and scalable generation of functional red cells' by Jan Frayne et al in Nature Communications.

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How the Cobra Found Its Venom

Image: King Cobra by Kevin Messenger: Middle Red-necked black spitting cobra Image: Randy Ciuros
 

|| March 19: 2017: Swansea University News || ά.  New research by a Swansea University scientist has examined why cobras have evolved to be the only snakes to spit deadly venom and how this is linked to other cobra behaviour, which may help to address the snakebite crisis in parts of Africa and Asia. Dr Kevin Arbuckle at the College of Science worked with an international team of collaborators and published in the journal ‘Toxins’ a study on cobras, a group of snakes that has evolved multiple times to ‘spit’ a tissue-destroying or ‘cytotoxic’, venom. This type of venom is unusual amongst the wider group of snakes cobras belong to, which more typically attacks the nervous system to paralyse their prey.

The study found that the way, in which cobras warn predators by rising up to face the threat and spreading its hood was important in driving the evolution of cytotoxic venom and the ability to ‘spit’ this into the eyes of predators. The results of the study suggest that cytotoxicity of a cobra’s venom evolved primarily as a defense mechanism and that this co-evolved twice alongside hooding behaviour: once in the ring-necked spitting cobra and ‘true’ cobras and again, independently, in king cobras. The researchers, also, found that the evolution of cytotoxic venom combined with hooding displays provided the selection pressure for spitting behaviour.

Although unique to cobras amongst venomous snakes, they found that spitting evolved independently three times within cobras, in the ring-necked spitting cobra and also, in both the African and Asian ‘true’ cobras.

The researchers, also, suggest that the bold and distinctive hood pattern of cobras, such as the famous spectacled cobra of India might act as an additional defensive warning that is associated with painful cytotoxic venom.

Dr Kevin Arbuckle, a Lead Author on the study, said, “It is known that in the developing world, snakebites affect the poor and young males, in particular, are at risk. Suffering a snakebite can result in lifelong disabilities from tissue-destroying venoms and render victims unable to carry out manual work and this represents a considerable socio-economic burden.

Our research seeks to understand the evolutionary pressure that shapes the activity of snake venoms and could help to address the snakebite crisis in sub-Saharan Africa and southern Asia by providing insights into snake behaviour and toxicity.

For instance, clinicians should not expect tissue damage only from spitters, when treating cobra bites and antivenom developers should, also, bear this variation in mind.”ω.

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New Map of the Protein Phosphatases: Is There an A-Z of Proteins Like the Periodic Table or the Genome: The Humanion Imaginasises

The human protein phosphatases are illustrated in the form of the most well studied phosphatase, the protein phosphatase 2A:PP2A. PP2A
is composed of the structural A and catalytic C subunits and a regulatory B subunit. When the PP2A catalytic C subunit associates with the A and B
subunits several protein isoforms, namely holoenzymes, are produced with distinct activity and substrate specificity. Image: M Varjosalo


 

|| March 18: 2017: University of Helsinki News: Päivi Lehtinen and The Humanion Writing || ά.  In a new study, a Finnish-Swiss research team report global quantitative interactomics analysis, covering half of the human protein phosphatome. Co-ordinated activities of protein kinases and protein phosphatases ensure phosphorylation homeostasis and amplitude of signalling response and understandably its imbalance is linked to diseases, such as cancer. Unlike with protein kinases, the current knowledge of protein phosphatase functions and especially, on their formed interactions and complexes remains fragmentary. As from the headline, the Reader, can guess, that The Humanion makes, not a hypothesis, but a hypothesis of imagination, therefore, imaginasis, verb: to imaginesise, to make a hypothesis, simply based on imagination, as if to offer a 'form of a skeletal structure', around which, a hypothesis might possibly be constructed, that poses the question to the research community of the world, whether there could and does exist an A-Z of all proteins, like the Periodic Table or the Genome or the Piano Keyboard?

In a study being published in the 26th of April issue of Cell Systems, which has been published ahead of the print publication, online on March 15, a Finnish-Swiss research team, led by Dr. Markku Varjosalo from the Institute of Biotechnology and University of Helsinki, report global quantitative interactomics analysis, covering half of the human protein phosphatome. They further derive and characterise the molecular functions and pathways, that the protein phosphatases connect via their stable or transient interactors. Furthermore, their study show novel physical, as well as, functional links to phosphatase-based regulation of human cancer.

"This study is a continuum of our almost a decade long efforts to systematically dissect the molecular mechanisms behind the protein phosphorylation. After our extensive analyses on protein kinases, the protein phosphatases were naturally to follow.

The protein phosphatases were too long thought to just be the negative counterpart of protein kinases, with promiscuous activity and low intrinsic substrate specificity. Recent studies, such as ours, however, establish protein phosphatases as positive and essential regulators of signal transduction, with remarkable substrate specificity and co-ordinated activities. The phosphatases are, also, promising targets for therapeutic intervention in the treatment of various cancers." Dr. Varjosalo states.

The study was financially supported by the Academy of Finland, University of Helsinki, The Sigrid Juselius Foundation, The Emil Aaltonen Foundation, the Swiss Initiative in Systems Biology:SystemsX.ch, Instrumentarium Science Foundation and the Cancer Society of Finland.

Further information: Adjunct Professor Markku Varjosalo: Tel. +358 29 4159413, email:markku.varjosalo at helsinki.fi:
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The Paper: Leena Yadav, Fitsum Tamene, Helka Göös, Audrey van Drogen, Riku Katainen, Ruedi Aebersold, Matthias Gstaiger, and Markku Varjosalo. Systematic Analysis of Human Protein Phosphatase Interactions and Dynamics-Cell Systems 4, 1–15, April 26, 2017, e-pub ahead of print March 15, 2017

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And How Does Dopamine Work the Brain

Blue indicates cell nuclei, green indicates dopamine neurons labeled with green fluorescent protein.

|| March 11: 2017: The Salk Institute News: La Jolla: San Diego: California: US || ά. In the March 9, 2017, online publication of the journal Neuron, scientists at the Salk Institute report that the concentration of a brain chemical, called, dopamine governs decisions about actions so precisely that measuring the level right before a decision, allows researchers to accurately predict the outcome. Additionally, the scientists found that changing the dopamine level was sufficient to alter upcoming choice. The work may open new avenues for treating disorders both in cases, where a person cannot select a movement to initiate, like Parkinson’s disease, as well as, those in which, someone cannot stop repetitive actions, such as obsessive-compulsive disorder:OCD or drug addiction.

“Because we cannot do more than one thing at a time, the brain is constantly making decisions about what to do next.” says Mr Xin Jin, an Assistant Professor in Salk’s Molecular Neurobiology Laboratory and the paper’s Senior Author. “In most cases our brain controls these decisions at a higher level than talking directly to particular muscles and that is what my lab mostly wants to understand better.” When we decide to perform a voluntary action, like tying our shoelaces, the outer part of our brain, the cortex, sends a signal to a deeper structure, called, the striatum, which receives dopamine to orchestrate the sequence of events: bending down, grabbing the laces, tying the knots.

Neurodegenerative diseases, like Parkinson’s, damage the dopamine-releasing neurons, impairing a person’s ability to execute a series of commands. For example, if you ask Parkinson’s patients to draw a V shape, they might draw the line going down just fine or the line going up just fine. But they have major difficulty making the switch from one direction to the other and spend much longer at the transition. Before researchers can develop targeted therapies for such diseases, they need to understand exactly what the function of dopamine is at a fundamental neurological level in normal brains.

Claire Geddes, Xin Jin and Hao Li

Mr Jin’s team designed a study in which mice chose between pressing one of two levers to get a sugary treat. The levers were on the right and left side of a custom-built chamber, with the treat dispenser in the middle. The levers retracted from the chamber at the start of each trial and reappeared after either two seconds or eight seconds. The mice quickly learned that when the levers reappeared after the shorter time, pressing the left lever yielded a treat.

 When they reappeared after the longer time, pressing the right lever resulted in a treat. Thus, the two sides represented a simplified two-choice situation for the mice, they moved to the left side of the chamber initially, but if the levers didn’t reappear within a certain amount of time, the mice shifted to the right side based on an internal decision.

“This particular design allows us to ask a unique question about what happens in the brain during this mental and physical switch from one choice to another.” says Mr Hao Li, a Salk Research Associate and the paper’s Co-first Author.

As the mice performed the trials, the researchers used a technique, called, fast-scan cyclic voltammetry to measure dopamine concentration in the animals’ brains via embedded electrodes much finer than a human hair. The technique allows for very fine-time-scale measurement, in this study, sampling occurred 10 times per second and therefore can indicate rapid changes in brain chemistry. The voltammetry results showed that fluctuations in brain dopamine level were tightly associated with the animal’s decision. The scientists were actually able to accurately predict the animal’s upcoming choice of lever based on dopamine concentration alone.

Interestingly, other mice that got a treat by pressing either lever, so removing the element of choice, experienced a dopamine increase as trials got under way, but in contrast their levels remained above baseline, didn’t fluctuate below baseline, the entire time, indicating dopamine’s evolving role when a choice is involved.

“We are very excited by these findings because they indicate that dopamine could also be involved in ongoing decision, beyond its well-known role in learning.” adds the paper’s Co-first Author, Christopher Howard, a Salk research collaborator. To verify that dopamine level caused the choice change, rather than just being associated with it, the team used genetic engineering and molecular tools, including activating or inhibiting neurons with light in a technique, called, optogenetics, to manipulate the animals’ brain dopamine levels in real time.

They found that they were able to bidirectionally switch mice from one choice of lever to the other by increasing or decreasing dopamine levels. Mr Jin says that these results suggest that dynamically changing dopamine levels are associated with the ongoing selection of actions. “We think that, if we could restore the appropriate dopamine dynamics, in Parkinson’s disease, OCD and drug addiction, people might have better control of their behaviour. This is an important step in understanding how to accomplish that.”