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Archive for the ‘Molecular Genetics’ Category

Infants, Immunity, Infections and Immunization – Duke Today

Monday, December 30th, 2019

This is the fourth of several posts written by students at the North Carolina School of Science and Math as part of an elective about science communication with Dean Amy Sheck.

Dr. Giny Foudas research focuses oninfant immune responses to infection and vaccination.

Her curiosity about immunology arose during her fourth year of medical school in Camaroon, when she randomly picked up a book on cancer immunotherapy and was captivated. Until then, she conducted research on malaria and connected it to her interest in pediatrics by studying the effects of the parasitic disease on the placentas of mothers.

As a postdoctoral fellow at Duke, shethen linked pediatrics and immunology to begin examining mother to childtransmission of disease and immunity.

Today she is an M.D. and a Ph.D. and amember of the Duke Human Vaccine Institute. Shes an assistant professor inpediatrics and an assistant research professor in the Department of Molecular Geneticsand Microbiology at Duke University School of Medicine.

Based on the recent finding that children of HIV-positive mothers are more susceptible to inheriting the disease, Fouda believes that it is important to understand how to intervene in passive immunity transmissions in order to limit them. Children and adults recover from diseases differently and uncovering these differences is important for vaccine development.

This area of research is personally important to her, because she learned from her service in health campaigns in Central Africa that it is much easier to prevent disease than to treat.

However, she believes that it is important to recognize that research is a collaborative experience with a team of scientists. Each discovery is not that of an individual, but can be accredited to everyones contribution, especially those whose roles may seem small but are vital to the everyday operations of the lab.

At the Duke Human Vaccine Institute, Fouda enjoys collaborating as a team and contributing her time as a mentor and trainer of young scientists in the next generation.

Outside of the lab, Fouda likes to spend time reading books with her daughter, traveling, decorating and gardening. If there was one factor that improve how science in immunology is conducted, she would stress that preventing disease is significantly cheaper than treating those that become infected by it.

Dr. Fouda has made some remarkable progress in the field of disease treatment with her hard working and optimistic personality, and I know that she will continue to excel in her objectives for years to come.

Post by Vandanaa Jayaprakash NCSSM 2020

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NHS England Boss Knighted in New Year Honours – Medscape

Monday, December 30th, 2019

Simon Stevens, head of NHS England becomes a Sir, leading this year's healthcare field in the 2020 New Year Honours List.

The recipients in healthcare are alongside stars of sport, entertainment, public service, politics, charity work, and "the outstanding achievements of people across the United Kingdom".

The knighthood for services to health and the NHS in England in this year's list came just days after a study in the BMJ found health professionals are underrepresented by the honours system.

The health, science, and technology sector accounts for around 14.6% of honours, the Cabinet Office said.

Royal Marsden NHS Foundation Trust chief executive Cally Palmer was already a CBE (Commander of the Order of the British Empire) but is now a dame for services to cancer medicine. She's also National Cancer Director for NHS England and NHS Improvement.

In a statement, she said: "I feel incredibly fortunate to work for the NHS and to be surrounded by brilliant teams making great strides in progress for people affected by cancer. My role is simply to enable them, and all our staff, to do what they do best.

"Weve seen exceptional and very significant advances in our knowledge and understanding about better ways of researching, treating and curing cancer in the time Ive been at The Royal Marsden and it is a joy and a privilege to be able to make these improvements for the benefit of patients in the NHS and worldwide through groundbreaking research."

Prof Lesley Regan, who stood down as president of the Royal College of Obstetricians and Gynaecologists earlier this month, also becomes a dame.

Her successor, Dr Eddie Morris said she was an inspiration. "In her time as President, Lesley has not shied away from controversy or criticism and has infinite energy when defending the rights of women."

There were other health related knighthoods; Chair of Genomics England, Jonathan Symonds became a Sir as did Dr Mene Pangalos, executive vice-president, Innovative Medicines and Early Development Biotech Unit at AstraZeneca for services to UK science.

Professor Dame Sally Davies, former chief medical officer for England, now UK Special Envoy on Antimicrobial Resistance (AMR) said on Twitter: "I am thrilled to be recognised in the New Year Honours with a Dame Grand Cross of the Order of the Bath.

"I owe this to the incredible teams I have worked with across the NHS, Govt, third sector, industry, public & global health. There is much to do on AMR so cannot stop yet."

Prof Alan Lehmann, research professor of molecular genetics at the University of Sussex, receives a CBE for services to medical science due to his research into xeroderma pigmentosum and cockayne syndrome.

There's a CBE for Dr Paul Lelliott, former deputy chief inspector of hospitals at the Care Quality Commission, for services to mental health.

Prof Karen Barker, clinical director for trauma and orthopaedics at Oxford University Hospitals, is awarded an OBE (Order of the British Empire). Dr Debra Adams, head of infection prevention and control (Midlands and East), NHS England and NHS Improvement, also gets an OBE for services to infection prevention and nursing.

World Dementia Envoy, Dr Dennis Gillings, is named Knight Bachelor for services to the advancement of dementia and life sciences.

To mark the start of the World Health Organisation's Year of the Nurse and Midwife in 2020, 12 nurses and five midwives receive OBEs, MBEs (Members of the Order of the British Empire), and BEMs (British Empire Medal).

This includes MBEs for midwife Nicolette Peel who supports women affected by cancer during pregnancy, and Elizabeth Evans, who developed special stoma care services.

Also marking the event, the Duchess of Cambridge sent an open letter of appreciation to all midwives for their "amazing work".

Kate wrote: "You are there for women at their most vulnerable; you witness strength, pain and unimaginable joy on a daily basis."

She described the time she spent behind the scenes at Kingston Hospital's Maternity Unit, saying: "It gave me a broader insight into the true impact you have on everybody you help."

She quoted, Florence Nightingale, whose 200th anniversary is marked in 2020: "I attribute my success to this: I never have or took an excuse" and it is that mantra that I have seen time and time again in all of my encounters with you. You dont ask for praise or for recognition but instead unwaveringly continue your amazing work bringing new life into our world. You continue to demonstrate that despite your technical mastery and the advancement of modern medicine, it is the human to human relationships and simple acts of kindness that sometimes mean the most."

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NHS England Boss Knighted in New Year Honours - Medscape

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Sussex University professor honoured by Queen – Brighton and Hove News

Monday, December 30th, 2019

A Sussex University professor has been recognised by the Queen in the New Year Honours List.

Alan Lehmann

Alan Lehmann, a Fellow of the Royal Society (FRS), has been made a CBE for services to medical science and to patients and families affected by xeroderma pigmentosum and Cockayne syndrome.

Professor Lehmann is research professor of molecular genetics whose research has helped to show how cells are able to repair damaged DNA and how these repair processes can go wrong in patients with certain genetic disorders.

The Royal Society said: His work has furthered our understanding of the links between DNA repair and cancer.

He identified a faulty gene that is responsible for the skin condition xeroderma pigmentosum (XP), which causes extreme sensitivity to sunlight and a strong predisposition to skin cancer.

He subsequently showed how mutations in the same gene can cause two other conditions that are clinically very different from XP.

He has developed diagnostic tests for XP and his laboratory runs a worldwide diagnostic service for XP, as well as Cockayne syndrome and trichothiodystrophy other conditions resulting from mutations in the same or related genes.

His XP diagnostic service is an integral part of the national XP multidisciplinary clinic.

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Dorit Oliver-Wolff on New Year’s Honour’s list – The Argus

Monday, December 30th, 2019

A HOLOCAUST survivor who won the hearts of the nation on a TV dating show has been honoured by the Queen.

As a child, Eastbourne resident Dorit Oliver-Wolff hid from the Nazis in a cellar without light or heating for nine months after her family fled Hungary in 1941.

Earlier this year she achieved fame after a heartwarming date on Channel 4 show First Dates.

Now the 84-year-old has been awarded the British Empire Medal for services to Holocaust education and awareness, having addressed embassies and governments around the world.

She said she was gobsmacked when she received the news.

My head is getting so big, she said.

When I lived in Novi Sad I always thought I lived in the biggest city in the world.

I didnt even know what England was, it was just a little faraway island. Now Im going to Buckingham Palace. Its really exciting.

Just because I have an accent doesnt mean I havent adopted this country, and I am so happy this country has adopted me.

Ms Oliver-Wolff said she wanted to spread the message that life is for living.

A lot of people are only concerned about what happens in front of their house or next door, she said. But what we need to learn is bad things dont happen to them, they happen to us.

Its not just the Jewish people who have had their Holocaust, but so many other groups too.

I love my public speaking and I always tell people life is for living, not for being nasty.

The Holocaust survivor was one of many to have been named in the 2020 New Year Honours list.

Former Argus reporter Annie Nightingale was awarded a CBE for services to radio as BBC Radio 1s longest-serving presenter.

Ms Nightingale, who previously received an MBE, first worked as a journalist in Brighton.

I was rather attracted to the idea of racing around in a sports car with front page news. Of course, it is very different from that in reality, she said. I was interviewing movie stars one day and somebody involved in a murder the next. It was an incredible beginning, it was a great grounding. I met a really amazing team of reporters, all destined for Fleet Street, so I really had to up my game.

Meanwhile 24-year-old Pevensey makeup artist Kaiya Swain earned a British Empire Medal for winning the gold medal for beauty therapy at the Worldskills championship. Ms Swain made her name at the 2017 skills Olympics in Abu Dhabi.

Now one of the best young role models in the country, she has her own home salon. Its incredible. Im so grateful. Ive spent four long hard years of training, she said. I work for myself and I have a salon at home.

I specialise in eyelash extensions and I offer a range of treatments.

The competition was for everyone from cooks and engineers to beauty therapists like me.

Veteran marathon runner Rosie Thompson was awarded an MBE for services to the Armed Forces.

The 62-year-old Hurstpierpoint resident has run more than 36 marathons as part of the Not Forgotten Association, which helps lonely veterans.

In her 21 years at the charity she has raised more than 250,000 for those in need. Im shocked but thrilled. Im just getting used to it, she said.

Im very aware that I get paid to work for a charity, and Ive always wanted to give something back.

Thats why I go out on the streets and run marathons. Its to give something back to the community.

Ms Thompson said she took inspiration from the veterans she helps.

What I like most about my job is seeing the progress of people injured, she said. Veterans who have been shot or lost limbs go on to climb Kilimanjaro.

They often say Im their inspiration, but theyre mine.

Brighton pensioner Peter Burrows receives a British Empire Medal for services to the citys community.

The 78-year-old has raised money for a food bank, an allotment, and a community garden in Queens Park.

But Mr Burrows said he was not worthy of the honour.

I dont think Ive done anything extraordinary. Im just doing my bit, he said. I do a lot of work for the church, I clean up litter, and I clear the pavements of ice just ordinary things that anyone would do. I havent got a clue who recommended me.

Meanwhile in the village of Lodsworth, Martin Lester was very surprised when he got news of his British Empire Medal.

The 76-year-old has helped building a village hall, a community shop, and Lodsworth Larder for sharing food.

But he felt the entire community deserved the award.

The larder was probably the best thing thats happened to this village, but it was the local pub that really helped out, he said.

Weve got one of the best village halls in Sussex that we keep updating and everyone in this village is fantastic. Ive been working on the parish council for 20 years and it has been a full team effort.

When I got the letter about the award I was told to keep schtum, which has been difficult. But its good fun.

University of Sussex Professor Alan Lehmann has been made a CBE for service to medical science.

The professor of molecular genetics has made groundbreaking research into two rare genetic conditions.

Jane Goldingham, 62, from Brighton, was awarded an MBE for services to social work. She has taken a leading role in East Sussex and across the South East to improve learning, practice and support for social workers.

She was a frontline social worker for 16 years, and more recently, she has worked in adult social care.

Samson Rattigan, 28, from Brighton, was awarded a BEM for services to young people and families from gypsy and traveller communities in Sussex.

And Lindfield charity chief Paul Ramsbottom has been given an OBE.

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Dorit Oliver-Wolff on New Year's Honour's list - The Argus

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Are you a chain smoker? Beware of blurry vision and diabetes – TheHealthSite

Monday, December 30th, 2019

Smoking is bad and it can affect almost every aspect of your life. Passive smoking is also as bad as active smoking. In fact, some of the effects of smoking cannot be reversed even after you stop. But if you stop, then, you bring down your risk of many unwanted health complications. A study at Uppsala University and Uppsala Clinical Research Center says that smoking alters several genes that can be associated with health problems for smokers, such as increased risk for cancer and diabetes. The journal Human Molecular Genetics published this study.

Health complications due to smoking is a leading cause of death globally. In fact, cigarette smoking causes more deaths today than any other diseases including HIV, accidents, drug and alcohol abuse and firearm mortality.

Let us take a look at how smoking affects your body.

Cigarettes contain nicotine that can reach your brain within seconds of lighting up. As it is a stimulant, it gives you an energy rush for a while, but once the smoke subsides, it can make your brain feel tired and crave for more kicks of energy and pleasure.

Smoking also alters your brains response to senses such as taste and smell and can make you want to eat less while you smoke. Any time that you do not smoke, your body goes into a withdrawal mode that can have a negative effect on your cognitive abilities and lead to depression, anxiety and restlessness. It can also trigger headaches, blurry vision and insomnia.

Your lungs help to filter out any harmful chemicals that you may inhale, but inhaling smoke over a long period of time can damage your lungs ability to do so. Even though you may cough frequently as a result of smoking, the toxins will still remain inside your lungs and can lead to various respiratory diseases such as cold, flu and other infections.

Smoking can have a significant impact on your digestive system and increases your risk of certain types of cancer, such as cancer of the pancreas, kidneys and the mouth. It can also cause inflammation of the gums, known as gingivitis as well as infection in the gums, also known as periodontitis. It is also directly related to poor oral health, and can cause oral decay, bad breath as well as loss of tooth earlier as compared to those who are not exposed to smoke.

Smoking can directly impact the way your body reacts to insulin and can put you at a higher risk of having insulin resistance. It means that if you are regularly exposed to smoke, your chances of developing type 2 diabetes are very high and you will develop complications related to diabetes faster as compared to those who are not exposed to cigarette smoke.

Smoking can restrict the flow of blood to vital organs in your body and can limit the ability of erection in males. It can also make it more difficult for you to reach an orgasm as your brain does not get enough stimulus from the act.

Smoking can also lead to various complications in your pregnancy, put you at risk of miscarriage, premature delivery and birth defects. Mothers with exposure to secondhand smoke during pregnancy have a higher risk of having babies who will be prone to sudden infant death syndrome (SIDS). Female smokers are also at a higher risk of reaching menopause earlier than those who do not smoke. They are more prone to cervical cancer.

Text sourced from zliving.com

Published : December 28, 2019 2:40 pm | Updated:December 28, 2019 2:40 pm

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Are you a chain smoker? Beware of blurry vision and diabetes - TheHealthSite

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Fatty food can restrict gut communication with body: Study – Yahoo India News

Monday, December 30th, 2019

Washington D.C. (USA), Dec 29 (ANI): A recent study has suggested that food items containing more grease and fat can put the communication between intestine and rest of the human body to stop.

A team of Duke researchers has discovered that a high-fat meal completely shuts down the communication for a few hours. After they observed using the fish to examine cells that normally tell the brain and the rest of the body what's going on inside the gut after a meal.

The cells they were looking at are the enteroendocrine cells, which occur sparsely throughout the lining of the gut, but play a key role in signalling the body about the all-important alimentary canal. In addition to releasing hormones, the cells also have a recently-discovered direct connection to the nervous system and the brain.

These cells produce at least 15 different hormones to send signals to the rest of the body about gut movement, feelings of fullness, digestion, nutrient absorption, insulin sensitivity, and energy storage.

"But they fall asleep on the job for a few hours after a high-fat meal, and we don't yet know if that's good or bad," said John Rawls, an associate professor of molecular genetics and microbiology in the Duke School of Medicine.

Since enteroendocrine cells are key player's indigestion, the feeling of being full and subsequent feeding behaviour, this silencing may be a mechanism that somehow causes people eating a high-fat diet to eat even more.

"This is a previously unappreciated part of the postprandial (after-meal) cycle," Rawls said.

"If this happens every time we eat an unhealthy, high-fat meal, it might cause a change in insulin signalling, which could, in turn, contribute to the development of insulin resistance and Type 2 diabetes."

To understand the silencing better, the researchers tried to break the process down step by step in zebra-fish, reports the study published in 'eLife'.

After they first sense a meal, the enteroendocrine cells trigger a calcium burst within seconds, initiating the signalling process.

But after that initial signal, there's a delayed effect later in the after-meal period. It's during this later response that the silencing occurs, said Rawls, who also directs Duke's Microbiome Center.

The silenced cells change shape and experience stress in their endoplasmic reticulum, a structure that assembles new proteins. It seems that these enteroendocrine cells, which are specialized to synthesise and secrete proteins like hormones and neurotransmitters, become overstimulated and exhausted for a while.

The team tried the high-fat diet on a line of germ-free zebrafish raised in the absence of any microbes and found they didn't experience the same silencing effect. So they began looking for gut microbes that might be involved in the process.

After screening through all the kinds of bacteria found in the gut, they saw that the silencing appeared to be the work of a single type of gut bacteria, called Acinetobacter. (ANI)

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Viewpoint: Timing Molecular Motion with an Optical Stopwatch – Physics

Friday, December 27th, 2019

December 23, 2019• Physics 12, 149

Experiments capture the motion of an ionized molecule with an unprecedented combination of spatial and temporal resolution.

The ionization of a molecule by light sounds simplethe light comes in, electrons get kicked out. But ask about the details of this processsuch as how the molecule reconfigures in responseand the theoretical picture is murky for all but a few textbook cases. A set of techniques for controlling and imaging molecules has now reached a new level of temporal and spatial resolution to provide some clarity. Markus Kitzler-Zeiler of Vienna University of Technology (TU Vienna) and colleagues imaged the wave function of a simple molecule as it responded to the loss of an electron [1]. Combining two state-of-the-art techniques, they produced a movie of the molecule that captured the movements of the molecules protons in 1 picometer ( 1012 m) incrementsa small fraction of the width of an atomand with 70 attosecond ( 71017s) resolution. The approach allows a test of ionization models in H2 and may lead to a better understanding of chemical processes in more complex molecules.

The researchers focus on the simple motion of protons in singly ionized molecular hydrogen ( H2+). With a simple structure of just two protons bound together by an electron, H2+is for molecular physics what the fruit fly is for genetics. In an experiment, the team prepares an ensemble of cold H2 molecules by injecting gas through a supersonic nozzle and into a vacuum chamber. When an H2 molecule is intercepted by a sufficiently strong laser pulse, the lasers electric field removes one electron, which sets the now weakly bound protons into an oscillatory motion mediated by the remaining electron. This oscillation would continue indefinitely, were it not for the still-present laser field, which causes the second electron to be ejected at some random time ( t) after the first. With nothing left to keep the protons together, their mutual repulsion pushes them apart in a Coulomb explosion [2].

The time between the first and second ionization is anywhere between 0 and about 5 fs, and it is the increasing separation between the two protons during this interval that the researchers image by combining two techniques (Fig. 1). In the first technique, they use their laser pulse as a sort of stopwatch that starts when the first ejected electron is detected and stops when the second ejected electron is detected. In fact, the pulse is just two cycles of elliptically polarized, 750-nm light, and its rotating electrical field vector serves as the ticking hand of a watch that makes a full rotation every 2.5 fs. The researchers can infer the ticks that dislodge the first and second electrons by measuring the direction that they escapea technique known as angular streaking [3].

The second experimental ingredient is a picoscope, which extracts the distance between the protons when the molecule explodes by measuring their kinetic energy. When the laser pulse strips off the second electron, each proton feels a 1r repulsive Coulomb potential. Each proton then slides down this potential by moving further away from its partner, gaining kinetic energy by an amount that depends on its initial distance from the other proton. The team measured this kinetic energy at the time of the explosion and compared it to the known potential, achieving an effective magnifying glass that sees the proton separation when the molecule breaks apart. Much like particle physicists, the researchers measured the kinetic energy of the protons by following their trajectories in electric and magnetic fields [4].

Each timed Coulomb explosion serves as a mini experiment. After roughly 10 million such experiments, the researchers reconstructed the proton-proton distance at several time intervals after the first ionization (Fig. 2). When viewed together, these reconstructions essentially provide a time-lapsed, picometer-resolution image of the molecular wave functionboth the separation between the protons and the protons quantum-mechanically smeared out position. Although this demonstration is primarily a proof-of-principle, the researchers were also able to use their precise mapping of the wave function to test and rule out two ionization scenarios for H2, known as shake-up and resonant multiphoton electronic excitations.

This is the first time an ionized molecule has been viewed with such high spatial and temporal resolution at once. Having validated this approach with the molecular fruit fly, the next step would be to apply it to more complicated and less studied species, particularly those that are of interest to chemistry, molecular biology, and medicine. Applying the picoscope to more complicated molecules will require knowledge of more complicated molecular potential surfaces. However, Kitzler-Zeiler and colleagues contend this is not a huge problem since such surfaces can be readily calculated, even if the molecular dynamics preceding the Coulomb explosion cannot. From my view, an interesting avenue to explore would be the process of quantum tunneling. When an electron is removed from the H2+ ion by the strong laser field, it spends time under the barrier of the ions potential [5]. But the length of time and the behavior of the ion during that time are fascinating unknowns that the new technique might potentially explore.

The art of molecular movie making has advanced significantly since the 1980s and 1990s, when Ahmed Zewail and his colleagues first used femtosecond laser pulses to make movies of molecular oscillations and chemical reactionsan accomplishment that was recognized with the 1999 Nobel Prize in Chemistry. Zewail adopted a pump-probe technique, where one pulse (the pump) excites a collection of molecules and a subsequent weaker pulse (the probe) samples changes in the molecular state. The inherent time resolution of his approach was on the order of the fs duration of the envelope of the laser pulsethe smooth rise and fall in intensity that modulates the much more rapidly varying optical cycles. By contrast, Kitzler-Zeiler and colleagues achieved a sub-fs probe by tapping into the carrier electric field, which rotates with the actual cycles of elliptically polarized light [6]. A further improvement might come from using available techniques to stabilize and exploit the relative phase between the carrier and the envelope [7]. This capability would allow the determination of not only the relative time between two ionization events, t, but also the absolute timing of the events. Nevertheless, with the relative timekeeping already in hand, the researchers have obtained an unprecedented view of both the position of a molecular wavepacket and its shape.

This research is published in Physical Review Letters.

Alexei Sokolov is a professor of Physics and Astronomy at Texas A&M, where he holds the Stephen Harris Professorship in Quantum Optics. He obtained an M.S. from Moscow Institute of Physics and Technology in 1994 and a Ph.D. in physics from Stanford University in 2001.His general expertise is laser physics, nonlinear optics, ultrafast science, and spectroscopy. Specific areas of interest include the generation of subcycle optical pulses with prescribed temporal shape; ultrafast atomic, molecular, and nuclear processes; and applications of molecular coherence in biological, medical, and securityoriented areas.

Vclav Hanus, Sarayoo Kangaparambil, Seyedreza Larimian, Martin Dorner-Kirchner, Xinhua Xie (), Markus S. Schffler, Gerhard G. Paulus, Andrius Baltuka, Andr Staudte, and Markus Kitzler-Zeiler

Phys. Rev. Lett. 123, 263201 (2019)

Published December 23, 2019

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Could a vaccine reduce the rate of Alzheimer’s? These Israelis think so – The Jerusalem Post

Friday, December 27th, 2019

A team of researchers from the Hebrew University of Jerusalem have successfully associated the Bacillus Calmette-Guerin (BCG) vaccine with reducing the risk of Alzheimers.The disease affects one in 10 adults over the age of 65 a number that is expected to triple by 2030, according to HU.BCG is the vaccine used to treat tuberculosis worldwide. Though in the past it was administered routinely in the United States, it is today mainly used in developing countries or with high-risk populations in Western countries.However, the vaccine has another use, according to Herv Bercovier of HUs Department of Microbiology and Molecular Genetics. Bercovier, who led the BCG study with colleagues Charles Greenblatt and Benjamin Klein, said that BCG is also used to treat and cure certain types of bladder cancer.Hebrew University Professor Herv Bercovier (Credit: Lior Mizrahi)People with bladder cancer tend to be 70 years or older, he explained to The Jerusalem Post, so they are close to the population that has an increased risk for developing Alzheimers.Furthermore, Bercovier explained, BCG has been shown to lower general chronic inflammation. Patients with Alzheimers suffer from chronic inflammation in the brain as a result of proteins that improperly unfold inside and outside of the brain.As such, the HU team followed 1,371 bladder cancer patients receiving treatment at HUs Hadassah-University Medical Center. During follow-up visits, 65 cancer patients had developed Alzheimers, a release explained. Those who had not received BCG as part of their treatment had a significantly higher risk of developing Alzheimers than did BCG-treated patients: 8.9% (44 patients) as opposed to 2.4% (21).Moreover, when compared with the general non-bladder cancer population, people who had never been treated with BCG had a four-fold higher risk for developing Alzheimers than did those who were treated with BCG.Theres data reaching back to the 1960s that shows that countries treating bladder cancer patients with the BCG vaccine had a lower prevalence of Alzheimers disease but it hadnt been properly analyzed, said Bercovier.With this study, he said he believes we are closer to understanding the vaccines impact.Bercovier noted that the next steps are to reproduce the study in different populations. Then, he said, to prove causality, the team will conduct a formal clinical trial.The findings of this study were published in PLOS ONE.

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Could a vaccine reduce the rate of Alzheimer's? These Israelis think so - The Jerusalem Post

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How Athletes Are Reaping the Benefits of Keto Without Actually Giving Up Carbs – Gear Patrol

Friday, December 27th, 2019

Youve definitely heard of the ketogenic diet starving your body of carbs to force it to burn fat and produce the mind-clarifying, brain-healing compounds known as ketones. You may have even heard of people and athletes ingesting ketone salts or drinks to propel them into or keep them in a state of ketosis. And if you were paying close attention during the Tour de France this year, you may have spied Team Jumbo-Visma openly drinking ketones mid-race.

The funny thing is, these athletes are not on a ketogenic diet. They are not fat adapted.

For the last three years or so, weve seen Tour athletes fueling with carbs and then supplementing with exogenous ketones to score a two to three percent boost in performance from dual-fueling, says Matt Johnson, a former competitive cyclist and co-founder of The Feed, an online sports nutrition shop and leading supplier of exogenous ketones in the U.S. June was insane with teams placing $10,000 to $20,000 orders for ketone esters and rush shipping them to France. We could barely keep up with it.

Elite athletes biohacking to score a tiny edge? Nothing new.

But this is: a study in the Journal of Physiology says everyday athletes who arent on a keto diet, who arent fat-adapted, may improve their recovery by a whopping 15 percent just from drinking exogenous ketones after intense training days. And the news is spreading.

We have also had a huge spike in individual athletes ordering the product that seems to be only growing, Johnson adds.

Now, will this approach work for you? Heres everything you need to know.

First, a quick biology lesson slash crash course in the trendiest diet of the twenty-teens: in an ideal world, your body breaks down carbohydrates into glucose, which is then transported and used or stored as energy for your muscles, organs and, most importantly, your brain.

Your brain is at the top of the pecking order it gobbles about 20 percent of your total energy expenditure, a lot for a single organ and if its not fueled, everything else stops functioning. When you deprive your body of carbohydrates, your muscles can use fat for fuel, but your brain cant. Instead, your body has a fail-safe to prevent total shutdown: the liver starts converting fat into a superfood designed to save your starving brain: ketones.

Even if your body can adapt to burning fat quickly to fuel long runs and rides, it would still prefer to burn carbs. Which is why the notion of pro athletes downing exogenous ketone drinks without having to give up carbs is completely bonkers.

Ketones are essentially a fourth macronutrient your blood sugar is stable, your body is burning fat and your brain has entered an almost elevated state of functionality. In ketosis the state you reach when adhering to a keto diet your brain starts producing more mitochondria (the little powerhouses of energy in your body) and better regulating neurons. Staying in a state of ketosis has been shown to help clear the brain of proteins that can lead to and worsen Alzheimers disease, reduce seizures in about half of people with epilepsy and even extend the lifespan of mice.

In athletes, staying in ketosis via a ketogenic diet can increase fat utilization during exercise (great, considering your body can store way more fat for fuel than carbs), help reduce body fat and sometimes improve endurance time trials and sprint peak power.

The catch: it all rides on you steering clear of carbs with no slip-ups. If you eat more than your allotted count typically 50 grams, which is one cup of pasta or just two bananas your body falls out of ketosis and you dont get any of these benefits. And pretty much all nutritionists agree that even if your body can adapt to burning fat quickly to fuel long runs and rides, it would still prefer to burn carbs.

Which is why the notion of professional athletes downing exogenous ketone drinks without having to give up carbs is completely bonkers.

In the early 2000s, as part of a DARPA program to enhance U.S. soldier performance, Oxford professors Kieran Clarke and Richard Veech set out to distill the exact molecular structure of one of the ketones our body produces. The resulting ketone ester is a specific molecule, butanedial, that converts directly to beta hydroxybutyrate, the ketone our liver naturally produces in the ketogenic state, when you digest it, explains Geoffrey Woo, co-founder and CEO of HVMN.

HVMN is currently the only company to produce ketone esters, as they lease the patent to Clarke and Veechs molecular structure.

Now, keto followers are probably familiar with other brands of keto drinks (usually based on MCT oil) and ketone salts. But esters are different than these aids. MCT oils dont produce ketones; they help put your body in a state of ketosis so it can start producing its own but since that requires carbohydrate starvation, thats not an option for dual-fueling athletes, Johnson explains.

Ketone salts, meanwhile, use beta hydroxybutyrate as well, but by their nature, theyre bound to a mineral. Because you have to take so much ketone to raise your blood levels enough to see an effect, youre also gaining a lot of mineral load. This leads to a lot of GI issues in athletes, explains Woo. That, plus the fact that the salts dont raise your ketone levels that much, leaves a lot of room for a superior product. There has been minimal testing on the aids but the HVMN esters have been tested and verified, Johnson says.

Ketone esters are a way to eat ketones directly thats going to convert 100 percent to ketones in your body, Woo adds.

Woo says professional athletes drinking exogenous ketones during a race report about a two to three percent increase in performance. That matters in an event like the Tour but the real benefit for athletes, especially everyone other than Egan Bernal or Geraint Thomas, seems to be in downing a bottle once the race is over.

The aforementioned Journal of Physiology study, conducted by seemingly impartial Belgian researchers, simulated a Tour with everyday athletes: 20 fit men trained twice a day (HIIT or intermittent endurance training in the morning, then 1.5- to 3-hour endurance sessions at night), six days a week for three weeks. Half drank a ketone ester after each workout while half drank a placebo.

After three weeks, the guys were shredded everyone showed signs of cardiovascular, hormonal and perceptual overreaching. But those who had taken ketone esters regularly had significantly less damage in all these areas, and on a two-hour endurance test, they were able to ride at a higher sustainable pace and produce more power in the final 30 minutes compared to guys who recovered regularly. All in all, researchers estimated the ketone esters helped improve recovery by 15 percent.

Mainly, its providing your body with another option for fuel, says Jonathan Scott, Ph.D., R.D., an assistant professor at the Uniformed Services University in Bethesda, Maryland who researches performance nutrition and dietary supplements.

You can still have your cake and eat it too. Athletes dont need to consume a diet thats extremely restrictive, and they can then consume exogenous ketones to introduce yet another fuel source the body can use.

Your brain is either going to use glycogen or ketones for power. If ketones are available, glycogen is spared and your muscles can instead use that energy to fuel fiber repair and metabolic cleanup. Whats more, now your body isnt going to break down other structures like muscle fiber to get your brain the fuel, saving your body extra damage.

And, because ketones keep your blood glucose stable, your body is steadily producing insulin, which sweeps glucose into your cells, continuously topping off the pool of energy as its being used and at a much faster rate than youre able to with food, Scott explains.

In addition to faster post-exercise glycogen replenishment, a 2018 Italian study in Current Sports Medicine Report foundthat exogenous ketones decrease proteolysis (the breakdown of proteins into amino acids) and act as metabolic modulators and signaling metabolites.

Theres also some chemistry research to suggest exogenous ketones may help realign your hormone production, adds Krista Austin, Ph.D., C.S.C.S., a sports scientist, exercise physiologist and nutritionist. The anterior pituitary produces hormones that become dysregulated if youre overtraining, dont sleep well at night, have a poor heat tolerance, or experience something like a traumatic brain injury, she explains. Exogenous ketones seem to help realign the production of susceptible hormones like prolactin, which can otherwise prevent proper sleep and recovery.

To top it off, it takes very minimal effort for athletes to earn all these gains: You can still have your cake and eat it too literally and figuratively, Scott explains. Athletes dont need to be consuming a diet thats extremely restrictive on food choices or energy sources during exercise, and they can then consume exogenous ketones to introduce yet another fuel source the body can use.

Johnson says its only a matter of time before major American sports stars pick up the training aid and that well definitely see it in the Olympics. Basketball and hockey especially have some grueling schedules. Imagine the benefit in-season for back-to-back games on the road?

Johnson estimates that roughly 80 percent of the interest in exogenous ketones on The Feed comes from Europe and about 60 percent of that is from non-elites.

For most amateur athletes, that 15 percent improvement in recovery means youll simply feel better after a grueling workout youll have less muscle soreness and stiffness, more energy, better range of motion and sleep better, says Austin.

But thats not necessarily the score it sounds like. If you dont feel terrible after a series of tough training days or a hard race, youre much more likely to get back out, sooner, Austin says. But you might do more harm than good. Until we understand better how exogenous ketones affect the body and recovery, numbing the alarm doesnt change the need for rest.

And will they even work for you like they do for the pros? Jurys still out. Everyday athletes are likely going to respond differently to exogenous ketones, considering just the impact of genetics and training on energy substrate metabolism (how well your body burns other fuel sources) alone, Scott says. And, as with all supplements or performance aids, there are very clearly responders and non-responders. It simply doesnt work for everyone, he adds.

But most importantly, there are so many other aspects of performance that everyday athletes would be better served to focus on, Scott points out, including but not limited to sleep, diet composition, diet quality, nutrient timing, hydration, training program, rest days, stress management, meditation, visualization and even social relationship quality. For elites, all these things are taken into consideration and already optimized, he says. But I would hate for an amateur athlete to start taking ketones to improve sleep for better recovery when its really their stress management that needs to be tweaked.

The upside: as long as you monitor everything above, all our experts agree, theres close to no risk in trying.

Pretty much everyone agrees you shouldnt be using exogenous ketones to enhance recovery after every hard workout or race. This isnt meant for a long weekend ride, Johnson cautions. Even if it was really hard and I came home completely bonked and exhausted, I dont need a ketone ester to feel better at work the next few days.

Not only will drinking it post-ride regularly lead to overtraining, but, at $37 a bottle, a few bottles a week doesnt make economic sense for most of us. The effects of exogenous ketones last roughly an hour after ingestion and youre intended to drink a whole bottle immediately after moving for recovery.

If a client is having trouble sleeping, Ill have them drink ketones before bed so their body can catch up on repairs. But its important to address the underlying issues of why theyre not sleeping in the bigger picture.

But when marathon training gets serious and youre logging 15K, 18K and 12K all within a few days? Thats when you want to take it. Harder training weeks, multi-day endurance competitions, multi-stage races I would absolutely be using it after every stage. That level of benefit is enormous, Johnson adds.

Austin agrees, but adds shell also use it sparingly to disrupt recovery inhibitors. If a client is having trouble sleeping, Ill have them drink ketones before bed for just a few nights so their body can catch up on repairs, she says. But its important to address the underlying issues of why theyre not sleeping in the bigger picture.

And while we have no studies on microdosing (which would be more approachable and more wallet-friendly), Austin says shes seen some results. If someone is new to training, that mid-morning fatigue can be debilitating in terms of getting work done, but taking 10 milliliters of ketones can give them an energy boost, she explains.

Everyone agrees, given the current state of research, exogenous ketones are generally safe. And the one high-quality product we have on the market now (HVMN) is good to go.

But its worth noting that exogenous ketones are currently sold as dietary supplements, which means theres no oversight by the FDA. As ketones become more popular and more formulas come to market, well inevitably see products packed with both other enhancements and other cost-cutting, potentially dangerous ingredients, Scott says. (The upside: the hefty price of formulas like HVMN will likely come down, too.)

We also dont know the effects or risks of using it long term is there a threshold after which exogenous ketones stop being as effective? If your body gets used to the aid in recovery, could it eventually stop being as efficient at rebuilding without it? Do you get any of the neuroprotective benefits of naturally going into ketosis? And, perhaps most importantly, if youre an ultra-runner or frequent multi-day racer using exogenous ketones for recovery, what nuanced alarm bells are you overlooking?

There are definitely a lot of unanswered questions when it comes to exogenous ketones. But with minimal risk and serious potential gains, we wouldnt knock anyone for giving a sip.

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2019: The year gene therapy came of age – Eyewitness News

Friday, December 27th, 2019

Victoria Gray's recovery from sickle cell disease, which had caused her painful seizures, came in a year of breakthroughs in one of the hottest areas of medical research -- gene therapy.

Picture: Supplied.

WASHINGTON, United States - In the summer, a mother in Nashville with a seemingly incurable genetic disorder finally found an end to her suffering -- by editing her genome.

Victoria Gray's recovery from sickle cell disease, which had caused her painful seizures, came in a year of breakthroughs in one of the hottest areas of medical research -- gene therapy.

"I have hoped for a cure since I was about 11," the 34-year-old told AFP in an email.

"Since I received the new cells, I have been able to enjoy more time with my family without worrying about pain or an out-of-the-blue emergency."

Over several weeks, Gray's blood was drawn so doctors could get to the cause of her illness -- stem cells from her bone marrow that were making deformed red blood cells.

The stem cells were sent to a Scottish laboratory, where their DNA was modified using Crispr/Cas9 -- pronounced "Crisper" -- a new tool informally known as molecular "scissors."

The genetically edited cells were transfused back into Gray's veins and bone marrow. A month later, she was producing normal blood cells.

Medics warn that caution is necessary but, theoretically, she has been cured.

"This is one patient. This is early results. We need to see how it works out in other patients," said her doctor, Haydar Frangoul, at the Sarah Cannon Research Institute in Nashville.

"But these results are really exciting."

In Germany, a 19-year-old woman was treated with a similar method for a different blood disease, beta-thalassemia. She had previously needed 16 blood transfusions per year.

Nine months later, she is completely free of that burden.

For decades, the DNA of living organisms such as corn and salmon has been modified.

But Crispr, invented in 2012, made gene editing more widely accessible. It is much simpler than preceding technology, cheaper and easy to use in small labs.

The technique has given new impetus to the perennial debate over the wisdom of humanity manipulating life itself.

"It's all developing very quickly," said French geneticist Emmanuelle Charpentier, one of Crispr's inventors and the cofounder of Crispr Therapeutics, the biotech company conducting the clinical trials involving Gray and the German patient.

CURES

Crispr is the latest breakthrough in a year of great strides in gene therapy, a medical adventure started three decades ago when the first TV telethons were raising money for children with muscular dystrophy.

Scientists practising the technique insert a normal gene into cells containing a defective gene.

It does the work the original could not -- such as making normal red blood cells, in Victoria's case, or making tumour-killing super white blood cells for a cancer patient.

Crispr goes even further: instead of adding a gene, the tool edits the genome itself.

After decades of research and clinical trials on a genetic fix to genetic disorders, 2019 saw a historic milestone: approval to bring to market the first gene therapies for a neuromuscular disease in the US and a blood disease in the European Union.

They join several other gene therapies -- bringing the total to eight -- approved in recent years to treat certain cancers and inherited blindness.

Serge Braun, the scientific director of the French Muscular Dystrophy Association, sees 2019 as a turning point that will lead to a medical revolution.

"Twenty-five, 30 years, that's the time it had to take," he told AFP from Paris.

"It took a generation for gene therapy to become a reality. Now, it's only going to go faster."

Just outside Washington, at the National Institutes of Health (NIH), researchers are also celebrating a "breakthrough period."

"We have hit an inflection point," said Carrie Wolinetz, NIH's associate director for science policy.

These therapies are exorbitantly expensive, however, costing up to $2 million -- meaning patients face gruelling negotiations with their insurance companies.

They also involve a complex regimen of procedures that are only available in wealthy countries.

Gray spent months in the hospital getting blood drawn, undergoing chemotherapy, having edited stem cells reintroduced via transfusion -- and fighting a general infection.

"You cannot do this in a community hospital close to home," said her doctor.

However, the number of approved gene therapies will increase to about 40 by 2022, according to MIT researchers.

They will mostly target cancers and diseases that affect muscles, the eyes and the nervous system.

**BIOTERRORISM **

Another problem with Crispr is that its relative simplicity has triggered the imaginations of rogue practitioners who don't necessarily share the medical ethics of Western medicine.

Last year in China, scientist He Jiankui triggered an international scandal -- and his ex-communication from the scientific community -- when he used Crispr to create what he called the first gene-edited humans.

The biophysicist said he had altered the DNA of human embryos that became twin girls Lulu and Nana.

His goal was to create a mutation that would prevent the girls from contracting HIV, even though there was no specific reason to put them through the process.

"That technology is not safe," said Kiran Musunuru, a genetics professor at the University of Pennsylvania, explaining that the Crispr "scissors" often cut next to the targeted gene, causing unexpected mutations.

"It's very easy to do if you don't care about the consequences," Musunuru added.

Despite the ethical pitfalls, restraint seems mainly to have prevailed so far.

The community is keeping a close eye on Russia, where biologist Denis Rebrikov has said he wants to use Crispr to help deaf parents have children without the disability.

There is also the temptation to genetically edit entire animal species -- malaria-causing mosquitoes in Burkina Faso or mice hosting ticks that carry Lyme disease in the US.

The researchers in charge of those projects are advancing carefully, however, fully aware of the unpredictability of chain reactions on the ecosystem.

Charpentier doesn't believe in the more dystopian scenarios predicted for gene therapy, including American "biohackers" injecting themselves with Crispr technology bought online.

"Not everyone is a biologist or scientist," she said.

And the possibility of military hijacking to create soldier-killing viruses or bacteria that would ravage enemies' crops?

Charpentier thinks that technology generally tends to be used for the better.

"I'm a bacteriologist -- we've been talking about bioterrorism for years," she said. "Nothing has ever happened."

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Fatty Meal Interrupts Gut’s Communication With The Body, But Why? – Duke Today

Tuesday, December 24th, 2019

DURHAM, N.C. -- A high-fat meal can silence communication between the intestine and the rest of the body, according to a new Duke University study in zebrafish.

While using the fish to examine cells that normally tell the brain and the rest of the body whats going on inside the gut after a meal, a team of Duke researchers discovered that a high-fat meal completely shuts down that communication for a few hours.

The cells they were looking at are the enteroendocrine cells, which occur sparsely throughout the lining of the gut, but play a key role in signaling the body about the all-important alimentary canal. In addition to releasing hormones, the cells also have a recently-discovered direct connection to the nervous system and the brain.

These cells produce at least 15 different hormones to send signals to the rest of the body about gut movement, feelings of fullness, digestion, nutrient absorption, insulin sensitivity and energy storage.

But they fall asleep on the job for a few hours after a high-fat meal, and we dont yet know if thats good or bad, said John Rawls, an associate professor of molecular genetics and microbiology in the Duke School of Medicine.

Since enteroendocrine cells are key players in digestion, the feeling of being full and subsequent feeding behavior, this silencing may be a mechanism that somehow causes people eating a high-fat diet to eat even more.

This is a previously unappreciated part of the postprandial (after-meal) cycle, Rawls said. If this happens every time we eat an unhealthy, high-fat meal, it might cause a change in insulin signaling, which could in turn contribute to the development of insulin resistance and Type 2 diabetes.

To understand the silencing better, the researchers tried to break the process down step by step in zebrafish.

After they first sense a meal, the enteroendocrine cells trigger a calcium burst within seconds, initiating the signaling process. But after that initial signal theres a delayed effect later in the after-meal period. Its during this later response that the silencing occurs, said Rawls, who also directs Dukes Microbiome Center.

The silenced cells change shape and experience stress in their endoplasmic reticulum, a structure that assembles new proteins. It seems that these enteroendocrine cells, which are specialized to synthesize and secrete proteins like hormones and neurotransmitters, become overstimulated and exhausted for a while.

The team tried the high-fat diet on a line of germ-free zebrafish raised in the absence of any microbes, and found they didnt experience the same silencing effect. So they began looking for gut microbes that might be involved in the process.

After screening through all the kinds of bacteria found in the gut, they saw that the silencing appeared to be the work of a single type of gut bacteria, called Acinetobacter. These bugs are normally less than 0.1 percent of the total gut microbiome, but they increased 100-fold after a high-fat meal and were the only bacteria able to induce the silencing effect.

Next we want to understand how Acinetobacter evokes this interesting response, said Lihua Ye, a postdoctoral fellow and lead author on this paper. We also suspect other bacteria might also have this capability.

Rawls said they arent sure why silencing occurs, nor whether it has any positive effect on the fish. It might be a way to prevent excessive signaling about the fat, but by being silenced completely like this, the cells wont be communicating anything else either.

We dont understand yet what the long-term impact of enteroendocrine silencing would be on metabolic health, Rawls said. This may be a maladaptive response to high-fat feeding that impairs the normal regulatory functions of these cells, leading to metabolic disorders like insulin resistance. But its also possible that the silencing is a beneficial adaptation to protect the animal from over-stimulation of the gut cells.

The study appeared as an accepted manuscript at the open-access journal eLife on Dec. 3. This research was funded by the National Institute of Diabetes and Digestive and Kidney Disease (R01-DK093399, R01 DK109368, R01-DK081426) and the Pew Charitable Trusts.

CITATION: High-Fat Diet Induces Microbiota-Dependent Silencing of Enteroendocrine Cells, Lihua Ye, Olaf Mueller, Jennifer Bagwell, Michel Bagnat, Rodger Liddle, John Rawls. eLife, Dec. 3, 2019. DOI: 10.7554/eLife.48479

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Scientists’ articles have been published in top journals – Mirage News

Tuesday, December 24th, 2019

The Department of Sports and Health Tourism, Sports Physiology, and Medicine of the Faculty of Physical Education has had its anniversary celebration 10 years from its founding. The staff of the department made a good gift for the anniversary: they published three articles in Q1 journals in the areas of medicine, biochemistry, genetics, and molecular biology.

2019 was a very busy year for the department: the team carried out two projects with the support of the Russian Science Foundation. The first is devoted to the study of myokines special proteins that are produced by muscles during physical exercise (the project manager is Professor Leonid Kapilevich, head of the department). In the second project, the effect of physical exertion on the compensation of type 2 diabetes mellitus was studied (the project manager is Professor Alexander Chibalin, a staff member of TSU and Karolinska Institute, Sweden). This resulted in 15 scientific articles in journals included in the international databases Web of Science and Scopus, including three articles in journals from the first quartile.

The article Transcriptomic Changes Triggered by Ouabain in Rat Cerebellum Granule Cells: Role of 3- And 1-Na +, K + -ATPase-mediated Signaling was published in PLoS ONE (the USA journal, impact factor 6.26, 27th of 2,836 journals in the category Medicine Myology). In this work, the role of monovalent ions (sodium and potassium) as regulators of intracellular processes was studied.

This is a fundamentally new approach, explains Leonid Kapilevich. Traditionally, calcium is considered the main ion that is the regulator of cellular metabolism, especially in muscles. However, the team showed that it is the ratio of sodium and potassium in the cell that is able to regulate the process of gene transcription, moreover, regardless of calcium.

The article Elevation of Intracellular Na + Contributes to Expression of Early Response Genes Triggered by Endothelial Cell Shrinkage was published in the journal Cellular Physiology and Biochemistry (published in Sweden, impact factor 5.11, 51stof 2,124 journals in Biochemistry, Genetics and Molecular Biology ). This article continues the research whose results are described in the previous article. Here, an attempt is made to understand how sodium ions affect the metabolic processes in the cell. It was found that one of the most likely ways is by changing the osmotic pressure of the cytoplasm and, as a consequence, the volume of the cell and its components.

The article Low AS160 and High SGK Basal Phosphorylation Associates with Impaired Incretin Profile and Type 2 Diabetes in Adipose Tissue of Obese Patients was published in the journal Diabetes Research and Clinical Practice (published in the Netherlands, impact factor 3.26, 26th of 133 journals in Internal Medicine). The study examined molecular changes in adipose tissue in patients with diabetes, which contribute to impaired glucose metabolism and can serve as a target for the therapeutic effect of exercise.

The tenth anniversary against the background of the centennials of other departments and faculties looks, of course, modest, but even for this short period the department has something to be proud of, says Leonid Kapilevich. During this time, two doctoral and nine masters theses were defended at the department, 15 student manuals were published, 115 articles were published in journals included in international databases, five monographs, and two grants from the Russian Science Foundation were won.

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Mosaic Angelman Should Be in Differential Diagnosis of AS, Study Says – Angelman Syndrome News

Monday, December 23rd, 2019

Clinicians should consider mosaic Angelman syndrome in the differential diagnosis of people who show milder symptoms of the disorder, a study suggests.

The study, Preserved expressive language as a phenotypic determinant of Mosaic Angelman Syndrome, was published in Molecular Genetics & Genomic Medicine.

Angelman syndrome (AS) is a genetic neurodevelopmental disorder usually associated with severe intellectual disability, difficulty speaking, loss of movement control (ataxia), and epileptic seizures. It is normally caused by the loss or malfunction of the maternal copy of the ubiquitin protein ligase E3A (UBE3A) gene in neurons from specific regions of the brain.

However, in some people, these genetic defects that affect the normal function of the UBE3A gene are only present in a handful of their cells. This phenomenon, known as mosaicism, can happen if one of the first cells of an embryo acquires a mutation in the UBE3A gene which is then passed on to their daughter cells as the embryo grows.

People with mosaic Angelman syndrome (mAS) typically have milder symptoms than those with Angelman syndrome. For instance, they experience milder expressive language delay with greater ability to attain meaningful words than typical Angelman patients.

In this study, researchers from the Vanderbilt University Medical Center and their collaborators set out to describe the clinical symptoms of mAS in a larger group of individuals to help clinicians with the differential diagnosis of Angelman syndrome.

The study included data from 22 people with mAS, whose caregivers filled out surveys at the medical center. Data from four additional patients was obtained from the Angelman Natural History Study, an observational study that followed the course of the disease in 302 Angelman patients over more than eight years. Clinical data from people with mAS was then compared to historical data from individuals with Angelman.

Findings revealed that nearly all mAS patients (90%) had some form of developmental delay. However, unlike those with Angelman, less than 15% of survey respondents said that mAS children showed signs of severe developmental delays before reaching the age of 1.

Compared with the significant language impairments seen in children with Angelman, 59% of the children with mAS retained the ability to articulate more than 20 words, with a fifth (20%) of them able to speak more than 1,000 words.

Other core features of Angelman, including ataxia, gait abnormalities, and limb tremulousness, were found in less than 33% of mAS children.

Additional clinical features of Angelman syndrome were also evident in patients with mAS: The three most prominent findings included abnormal sleep/wake cycles and decreased sleep in 73% of patients, followed by obesity in 64% of patients and heat sensitivity in 45% of patients, the researchers wrote. Constipation, a common problem in [Angelman syndrome] patients was also noted in the mAS cohort, with 72% of patients endorsing constipation.

Although children with mAS had milder speech impairments and were better able to engage in daily activities, they still faced many behavioral challenges that were typical in Angelman syndrome.

Anxiety was the most frequently endorsed behavior reported in our cohort, present to some degree in 95% of mAS patients and rated as severe in 43% of patients. Hyperactivity was commonly endorsed, reported in 59% of patients, the researchers wrote.

Overall these data encourage specialists to broaden the clinical features of [Angelman syndrome], said the researchers, who added that clinicians should consider tests to rule out mAS in individuals with developmental delay, hyperactivity, anxiety, and an uncharacteristically happy demeanor.

Joana is currently completing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. She also holds a BSc in Biology and an MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells cells that make up the lining of blood vessels found in the umbilical cord of newborns.

Total Posts: 11

Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

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Cancer therapy may be aided by induced macropinocytosis, a rarely reported form of cell death – The Mix

Monday, December 23rd, 2019

In preclinical experiments, a metabolic inhibitor killed a variety of human cancer cells of the skin, breast, lung, cervix and soft tissues.

In preclinical experiments, a metabolic inhibitor killed a variety of human cancer cells of the skin, breast, lung, cervix and soft tissues.In laboratory experiments, a metabolic inhibitor was able to kill a variety of human cancer cells of the skin, breast, lung, cervix and soft tissues through a non-apoptotic route catastrophic macropinocytosis.

In mouse xenograft studies, the inhibitor acted synergistically with a common chemotherapy drug, cyclophosphamide, to reduce tumor growth. Thus macropinocytosis, a rarely described form of cell death, may aid in the treatment of cancer.

Understanding the signaling pathways underlying macropinocytosis-associated cell death is an important step in developing additional effective strategies to treat neoplasms that are resistant to apoptosis induced by chemotherapy, said Mohammad Athar, Ph.D., professor in the University of Alabama at Birmingham Department of Dermatology.

The inhibitor, OSI-027, affects the mTOR pathway, which plays a critical role in regulation cellular growth and metabolism. Significantly, this potent inhibitor simultaneously targets two distinct protein complexes of the mTOR pathway, mTORC1 and mTORC2. Aberrant activation of these components has been associated with many cancer types.

Macropinocytosis starts with formation of ruffles on the surface of a cell that reach out from the cell membrane. These ruffles then fuse back with the cell membrane, creating a bubble that holds extracellular fluid, and the bubble moves inside the cell to become a vacuole filled with fluid. In catastrophic micropinocytosis, large numbers of these vacuoles form inside the cell and then fuse together, causing cell death.

The UAB researchers showed that dual inhibition of the two mTORC1 and -C2 complexes was necessary for highly effective cell death through macropinocytosis.

In early experiments, the researchers found that OSI-027, and a related dual inhibitor, PP242, induced extensive vacuolization in a wide range of human cancer cell lines, including two subtypes of rhabdomyosarcoma. These vacuoles were then shown to be macropinosomes.

Xenograft mouse experiments with human rhabdomyosarcoma tumors showed that OSI-027 blocked tumor growth by inducing macropinocytosis; furthermore, the addition of the chemotherapy agent cyclophosphamide acted synergistically to enhance efficacy of tumor size reduction.

Mohammad Athar, Ph.D.In mechanistic studies, Athar and colleagues found that macropinocytosis depended on activation of the MAP kinase MKK4, which was induced by the presence of reactive oxygen species. However, the full role of MKK4 is not well understood, they say.

Previous work by others had shown that several specific inducers of macropinocytosis induced macropinocytosis mainly in glioblastomas and colorectal cells. In contrast, Athar said, our study demonstrates that the dual inhibitors we tested induce catastrophic vacuolization in tumor cell lines from a wide range of organs, including skin, breast, cervix, lung and soft tissues.

The effects were much less pronounced in immortalized human keratinocytes.

Our data reveal that therapeutic targeting of mTORC1 and mTORC2, together with standard care treatment, Athar said, may be an effective approach to block the pathogenesis of recurrent rhabdomyosarcoma and perhaps other drug-resistant invasive neoplasms of diverse tissue types as well. The underlying mechanism by which tumors become responsive to treatment involves macropinocytosis, a unique form of cell death.

Co-authors with Athar of the study, Combined mTORC1/mTORC2 inhibition blocks growth and induces catastrophic macropinocytosis in cancer cells, published Proceedings of the National Academy of Sciences, are Ritesh K. Srivastava, Changzhao Li and Jasim Khan, UAB Department of Dermatology; and Louise T. Chow and Nilam Sanjib Banerjee, UAB Department of Biochemistry and Molecular Genetics.

Support came from National Institutes of Health grant ES026219 and funds from the Anderson Family Endowed Chair through UAB.

At UAB, Athar holds the Eric W. Baum, M.D., Endowed Professorship in Dermatology, and Chow holds the Anderson Family Chair in Medical Education, Research and Patient Care in the School of Medicine. Both are senior scientists in the ONeal Comprehensive Cancer Center at UAB.

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An Alzheimer’s research pioneer, right here at Penn – Penn: Office of University Communications

Monday, December 23rd, 2019

A primary project for Garrett Gibbons, a postdoctoral researcher at the Center for Neurodegenerative Disease Research (CNDR), is to develop novel tau antibodies as possibletherapies to treat Alzheimers disease. When in the thick of it, the scientific process becomes a huge, timelyand sometimes redundanttask.

One particular experiment comes to mind: Gibbons and his colleagues were injecting tau into mice models, which the mice developed antibodies against, and when they were harvested, the cells were paired with another cell to make a hybridoma. The problem? After two times running the full experiment, the antibodies still didnt meet certain criteria to be applicable.

Gibbons, quite disheartened, told his adviserVirginia Man-Yee Lee, a Perelman School of Medicine professor and director of CNDR, that the benchmark was too high.

Virginia was like, Well, try again, Gibbons recalled. She pushed back and said how she thought we could do better.

Although admittedly frustrated at the time, Gibbons rethought the project, and, ultimately, underwent a revamped test a third time.

And we got better antibodies, performing better than the previous ones, he said. They are now the candidates that we are evaluating as immunotherapy in mice, as potential treatments for Alzheimers disease.

It is safe to say, noted Gibbons, that without this kind of persistence from Lee, Alzheimers research wouldnt be nearly as developed as it is today. A pioneer in the field of neurodegenerative diseases, Lee was recently recognized for her four decades of work with a $3 million Breakthrough Prize in Life Sciences, an award backed by major technology leaders from companies including Google and Facebook.

Growing up in Hong Kong in a very traditional Chinese family, my mother never wanted me to become a professional, let alone a scientist, Lee said to the crowd, while accepting her Breakthrough Prize at the Oscars of Science in Silicon Valley in early November. Thankfully John Trojanowski, my life partner and collaborator, convinced me to embark on this wonderful journey with him, identifying proteins that are involved in devastating neurological diseases, which affect more and more of us, but have no effective treatment.

Lee, with a background in biochemistry and neuroscience, and Trojanowski, who studied pathology and neuropathology, have toiled alongside each other at Penn since the mid-1980s. They began work in Alzheimers research when it was very uncommon to do soin fact, their mentors urged them to stay far, far away from it.

What [our mentors] saw as a swamp, said Trojanowski, we saw as a huge challenge and opportunity that has led to an engaging career.

Before Lee and Trojanowski, prior studies had determined that an Alzheimers patients brain progressively accumulates plaques, abnormal clusters of protein fragments called beta-amyloid, that build up between nerve cells, and tangles, which form inside dying cells. Using this as a starting point, the duo detected their first major finding in 1991: that tau is the building block protein of the neurofibrillary tangles.

In 1997, Lee and Trojanowski found that Lewy bodies, the hallmark brain pathology of Parkinsons disease, are formed by alpha-synuclein. Knowing what causes Lewy bodies is important to Alzheimers researchers because about 50 percent of Alzheimers patients have Lewy bodies that contribute to cognitive deficits.

Then, in 2006, they discovered the pathological protein deposits in amyotrophic lateral sclerosis, or ALS, and frontotemporal degeneration, or FTD, are formed by TDP-43, a multifunctional DNA- and RNA-binding protein, and these deposits are also present in a large number of Alzheimers patients brains.

Lee was specifically recognized for the Breakthrough Prize for discovering TDP-43 protein aggregates in FTD and ALS, and revealing that different forms of alpha-synuclein, in different cell types, underlie Parkinsons disease and Multiple System Atrophy.

This is exceptionally important work, and we are very proud that it is taking place at Penn. Penn President Amy Gutmann

The discoveries led by Dr. Lee and her team are extraordinary, and absolutely worthy of the prestigious Breakthrough Prize, said Penn President Amy Gutmann, who went to Silicon Valley to support Lee in receiving her honor. Dr. Lee and her team have worked to fully understand the different segments of Alzheimers disease and other related disorders, using that knowledge to develop models that are becoming the foundation for therapies that will, hopefully, stop or reverse these diseases. This is exceptionally important work, and we are very proud that it is taking place at Penn.

Its rewarding, Lee said, to reflect on how researchers are becoming increasingly interested in TDP-43s involvement in neurodegenerative diseases, and the biology that is able to follow, now.

It is gratifying that people can, and people are very interested in, using the system that weve built to identify potential therapies, Lee explained. I am really optimistic that maybe some treatment for Alzheimers and Parkinsons will become available in the next, lets say, one or two decades.

Gibbons, who can distinctly remember being a teenager and watching his grandfather cope with all the stages of Alzheimers, as well as the impact it had on his family, knew rather early it would be a field he would want to pursue. But, it wasnt until he was immersed in the research that he realized how complicated it really was.

When I first got to Penn, I was kind of blown away with the challenge and sort of became cynical and pessimistic, Gibbons said. But I like the way that Dr. Lee continues to forge ahead and isnt overwhelmed as a young investigator, that gives me a lot of inspiration and hope. Of course there will be failures, and of course science is hard. This is worthwhile, and we will get there.

In terms of Lee as a leader, Mike Henderson, a research associate in her lab, said he appreciates the way she guides him in his learning, but also provides him with the independence needed to encourage innovative, out-of-the box thinking.

She really shows you what it takes to be a good scientist in the field, he said, adding how inquisitive Lee always is. Shes very curious and I think thats really what has driven her lab and what has made her so successful.

The main reason Henderson came to Penn, he noted, was to work not only with Lee and Trojanowski, but also with the team theyve assembled through the creation of the CNDR, which celebrated its 25th year in 2018. About 50 people are part of the center today.

From the Maloney Building on Penns campus, where CNDR is housed, Lee and Trojanowski have been able to foster multidisciplinary collaborations between basic and clinical scientists, and provide resources to enable the very best research projects, including a brain and biosample bank, a drug discovery program, data management and biostastic support, and expertise in biochemistry, histology, molecular biology, microscopy, tissue culture, and genetics.

John and I spent a lot of time developing an infrastructure to do this type of work, and Penn has been such a fantastic environment, said Lee, who acknowledged all of her collaboratorsstudents, postdocs, and staff scientistsat the Breakthrough event. I truly want to thank them for their dedication and commitment, she said.

Talking later, Trojanowski added, They have made possible all that we have accomplished.

There is no doubt about it: Talking about his beloved wife of 40-plus years is probably one of Trojanowskis favorite things to do. Shes always pushing herself to be better, and shes always pushing me to be better. She is driven, hardworking, very bright, determinedall of the things that you expect to see and need to see in people that are going to be as successful as she is.

Not only is she passionate about science, he adds, shes determined to solve any problem she ever sets her eyes on. Plus, shes an amazing preceptor, trainer, encourager of science in young people. She is just exceptional, he added.

Trojanowski attended the Breakthrough event with his wife, thrilled to stand by her side on such an exciting day. Its an outstanding recognition, he said.

One might think a $3 million check in the bank could be a ticket out of work, but for Lee, she was back in Philadelphia after just a couple days. As always, she rode her bike to the officeready and willing to take on her next challenge.

What Id like to do in the next 10 to 20 years, Lee said, is really work with companiespharmaceutical companies and biotechnology companiesto come up with treatments.

Virginia Man-Yee Lee is the John H. Ware 3rd Endowed Professor in Alzheimers Research in the Department of Pathology and Laboratory Medicinein the Perelman School of Medicine.

John Q. Trojanowski is the William Maul Measey - Truman G. Schnabel, Jr., M.D. Professor of Geriatric Medicine and Gerontology in the Department of Pathology and Laboratory Medicinein the Perelman School of Medicine.

The Breakthrough Prize in Life Sciences, founded in 2013, honors transformative advances toward understanding living systems and extending human life. It is sponsored by Sergey Brin, Priscilla Chan and Mark Zuckerberg, Pony Ma, Yuri and Julia Milner, and Anne Wojcicki.

Homepage photo: Today, about 50 people make up the Center for Neurodegenerative Disease Research, led by Lee and Trojanowski, who both expressed how thankful they are for such a great team.

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An Alzheimer's research pioneer, right here at Penn - Penn: Office of University Communications

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Quotes of the year – Spectrum

Monday, December 23rd, 2019

When we have this process thats really convoluted and complicated, its always the families with the least privilege who dont make it through.

Katharine Zuckerman, Oregon Health and Science University, on the challenges of getting an autism diagnosis and treatment in the United States.

If they find something that fits their argument, they emphasize it and make a point about it, and if they find something that doesnt fit their argument, they tend to put it aside.

Arthur Beaudet, Baylor College of Medicine, on researchers tendency to pick and choose what to include in a study.

Thats pretty good evidence when you poke it and it jumps, and you keep poking it and it jumps higher that youre on to a causal relationship.

Joy Hirsch, Yale University, on her teams findings that direct eye contact activates a region of the social brain.

Until we attend to the full diversity of autistic traits in confluence with gender, sexuality, culture, ethnicity, race, class, we will continue to miss people, and they will continue to feel lost.

Rua M. Williams, a nonbinary graduate student at the University of Florida, on the need to recognize the full spectrum of people with autism.

Im thinking of introducing a unicorn as our mascot. Who doesnt like magic and a bit of good luck to go with their science?

Annie Ciernia, University of British Columbia, on the ideal lab mascot.

Sitting in a room for two days thinking of nothing else but these children and their parents and the issues they have, and seeing them firsthand, gives you insight you just cant get any other way.

Stephan Sanders, University of California, San Francisco, on the value of attending meetings with families whose children share a rare genetic diagnosis.

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Quotes of the year - Spectrum

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Greasy Meals May Intervene Gut Action And Hinder Intestinal Activity – NDTV Food

Monday, December 23rd, 2019

Do you love your tall, meat and cheeseburger? You may want to think again before grabbing your next greasy treat. According to a latest study, a meal packed with a lot of fat and grease may silence the communication between the intestine and the rest of your body.

The researchers used fish to examine the cells that signal and tell the brain and the rest of the body what's going on inside the gut after a meal. The team discovered that a high-fat meal completely shuts down that communication for a few hours. The study published in 'eLife'.

The scientists were looking at the enteroendocrine cells, which occur sparsely throughout the lining of the gut. They happen to play a key role in signalling the body about the all-important alimentary canal. These cells, also have a recently-discovered direct connection to the nervous system and the brain. They produce up to at least 15 different hormones to send signals to the rest of the body about gut movement, feelings of fullness, digestion, nutrient absorption, insulin sensitivity, and energy storage. Hence their communication with rest of the body is imperative.

"But they fall asleep on the job for a few hours after a high-fat meal, and we don't yet know if that's good or bad," said John Rawls, an associate professor of molecular genetics and microbiology in the Duke School of Medicine.

Since enteroendocrine cells are key players indigestion, the feeling of being full and subsequent feeding behaviour, this silencing may be a mechanism that somehow causes people eating a high-fat diet to eat even more.

"This is a previously unappreciated part of the postprandial (after-meal) cycle," Rawls said.

"If this happens every time we eat an unhealthy, high-fat meal, it might cause a change in insulin signalling, which could, in turn, contribute to the development of insulin resistance and Type 2 diabetes."

To understand the silencing better, the researchers tried to break the process down step by step in zebra-fish, reports the study published in 'eLife'.

Once they sense a meal, these cells trigger a calcium burst within seconds, initiating the signalling process.

However after the initial signal, there's a delayed effect later in the after-meal period. The scientists said that it's during this later response that the silencing takes place.

The silenced cells have to potential change shape and experience stress in their endoplasmic reticulum. These enteroendocrine cells tend to become overstimulated and exhausted for a while, which hinders the action.

(This content including advice provides generic information only. It is in no way a substitute for qualified medical opinion. Always consult a specialist or your own doctor for more information. NDTV does not claim responsibility for this information.)

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Greasy Meals May Intervene Gut Action And Hinder Intestinal Activity - NDTV Food

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Biochemistry and Molecular Biology Degree Fully Accredited by ASBMB – UMass News and Media Relations

Sunday, December 15th, 2019

The American Society for Biochemistry and Molecular Biology (ASBMB) recently awarded full accreditation to the UMass Amherst biochemistry and molecular biology B.S. degree.

Aspects of the departments application that were considered particularly noteworthy according to the society include excellent faculty, outstanding in both teaching and research, integration of programs that promote student teamwork and communication skills, career advising and the advanced course-based undergraduate research experience (CURE) allowing students to gain authentic research experiences.

Jennifer Normanly, head of the department, says, Students who graduate from an ASBMB-accredited program have the opportunity to take an assessment, an exam, to have their degree certified by ASBMB, showing prospective graduate schools and potential employers that the students have met the societys high academic standards.

Dean Tricia Serio of the College of Natural Sciences said of the accomplishment, I am thrilled to see this well-deserved recognition for our stellar undergraduate major in biochemistry and for the departments leadership in and dedication to preparing our students for successful careers in the life sciences.

ASBMB, based in Rockville, Maryland, was founded in 1906 to advance the science of biochemistry and molecular biology through publication of scientific and educational journals, the organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels and by promoting the diversity of individuals entering the scientific workforce. It publishes three peer-reviewed research journals covering research in microbiology, molecular genetics, RNA-related research, proteomics, genomics, transcription, peptides, cell signaling, lipidomics and systems biology. The society has over 12,000 members and has awarded accreditation to 85 colleges/universities.

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Biochemistry and Molecular Biology Degree Fully Accredited by ASBMB - UMass News and Media Relations

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Prof. recognized for her contributions to science – The Justice

Sunday, December 15th, 2019

Biology Department chair and Prof. Piali Sengupta (BIOL) was one of 443 recently elected Fellows of the American Association for the Advancement of Science in 2019.

On Nov. 26, the AAAS published a full list of all elected fellows, who come from different universities and study a broad range of subjects. The AAAS is the worlds largest general scientific society and is located in Washington, D.C.

The AAASs article explains that fellows represent the 24 fields, from social, economic and political sciences to the natural sciences, such as biological and medical sciences. Past notable fellows include inventor Thomas Edison in 1878, anthropologist Margaret Mead in 1934 and computer scientist Grace Hopper in 1963. Fellows are elected by their peers on the Council of AAAS, the governing body of the organization. AAAS began selecting fellows in 1874.

According to a Nov. 26 BrandeisNow article, the AAAS sent Sengupta an acceptance letter explaining why she received the honor. The letter said she was chosen for her distinguished contributions to the field of sensory neuroscience, particularly for defining the molecular genetics of chemical communication and thermosensation in C. elegans.

Sengupta runs a lab that is broadly grouped into two areas, according to her Brandeis staff biography. The first is looking at the model organism C. elegans to see its response attraction or aversion to stimuli, like changes in temperature and changes to the chemicals in its environment. Called the Axis of Taxis subgroup, they investigate the neuronal, molecular and circuit mechanisms by which this organism responds to the stimuli. This is the part of her research she was recognized for.

The second subgroup in the Sengupta lab looks in the cilia, the part of the neuron that has the signalling molecules to allow for chemical signal transduction. Those who work on this project are known as the Cilia Squad and investigate the morphological and functional properties of the sensory cilia by looking at their cellular and molecular mechanisms. The lab overall looks at the animals sensory experience through genetic, molecular and neuronal mechanisms to see how they respond to complex and changing environments. It is for these contributions that Sengupta was elected as an AAAS Fellow.

Sengupta said that she is honored to be elected as an AAAS fellow because of its mission of inclusivity. She told BrandeisNow, AAAS has a strong commitment to promoting science research, policy and education as well as to increasing diversity and inclusion in STEM fields. As a Fellow, I look forward to contributing to these missions.

As Sengupta said, the AAAS has a longstanding tradition of inclusivity. According to its website, AAAS is committed to ensuring that everyone has the opportunity to contribute to, and benefit from, science and engineering by encouraging the recruitment, development, and retention of scientists. The organization seeks to provide tools that expand access to STEM education, strengthen and diversify the science and technology workforce, and amplify underrepresented and marginalized voices within STEM.

The 443 electees will be honored with official certificates and blue and gold rosette pins, which symbolize science and engineering. The ceremony will take place on Feb. 15, 2020 in Seattle, WA.

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Prof. recognized for her contributions to science - The Justice

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EPA’s ‘transparency rule’ is bad for science and the environment – STAT

Sunday, December 15th, 2019

A proposed rule by the Environmental Protection Agency (EPA) that allegedly aims to strengthen transparency in regulatory science suggests that science is broken. It isnt.

We know it works because we can see the life-saving transplant technologies, hurricane forecasts, new medications, pest-resistant crops, and countless other breakthroughs that exist because of science. This discipline isnt perfect, but it is the best tool available to safeguard the planet and its people.

Last year, the EPA proposed a rule requiring that scientists disclose all raw data before any study conclusions would be considered. The rule, titled Strengthening Transparency in Regulatory Science, would apply retroactively to regulations already in place. It would make it harder to enact new regulations, because many studies from the past rely on personal medical information that was collected under confidentiality agreements and include consensus from reports that may not have shared all of the data according in ways compliant with the proposed rule.

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The EPA has received nearly 600,000 comments on the proposed rule.

The House Committee on Space, Science, and Technology recently held hearings on the transparency rule and, in a bipartisan show of support, advanced out of committee the Scientific Integrity Act. This legislation would require all federal agencies that conduct or use science to set up systems to address and better yet, prevent attacks on science, like the EPAs proposed rule. Please contact your representatives in Congress to support the Scientific Integrity Act.

Scientists like us have been raising our voices in opposition to a rule rooted in the misconception that science leaps to conclusions based on weak evidence in single papers. In reality, science works because it produces ideas that are continually tested under tremendous critical scrutiny over long periods of time.

We are writing not just for ourselves but on behalf of other leaders in open and reproducible science practices: Todd Vision, professor and founder of the Dryad Digital Repository; Laurie Goodman, editor-in-chief of the open-access journal GigaScience; Elizabeth Iorns, CEO of Science Exchange and the codirector of the Reproducibility Initiative; Carly Strasser, director of alliances and data strategy at the Fred Hutchinson Cancer Research Center; and Mark Johnston, editor-in-chief of the journal Genetics and former chair of the department of biochemistry and molecular genetics at the University of Colorado.

We are a group of scientists dedicated to accelerating discovery and improving the rigor, transparency, and reproducibility of research. So it may be surprising that we are writing in opposition, as others have done, to a rule whose title would lead one to think its good for science. We oppose it because it wont do what it alleges to do: increase transparency or improve the health and safety of people or the environment.

Various stakeholders in science including researchers, funders, publishers, private organizations, and various public groups are constantly working to maintain and improve the integrity of scientific research. The proposed EPA rule may seem on the surface to support that goal. But it is instead a misguided proposal that undercuts the ongoing efforts of the scientific community in favor of dangerous vetting by a regulatory agency that will not have access to the best information.

Moreover, the Office of Management and Budget estimated that complying with the transparency rule would initially cost $250 million, and then between $1 million and $100 million a year, making it an expensive boondoggle that reduces the quality of information available to EPA policymakers.

Independent validation and replication of the research on which significant regulatory actions are based is a worthwhile goal. But that wouldnt happen under the EPAs rule. Research journals are increasingly implementing data availability policies that, unlike this rule, dont impose onerous burdens on researchers and EPA administrators and that respect the need to protect the privacy of human subjects when sensitive public health data are involved.

In an editorial in PLOS Medicine, Stanfords John Ioannidis writes, If the proposed rule is approved, science will be practically eliminated from all [EPA] decision-making processes. Regulation would then depend uniquely on opinion and whim. This would be devastating to the EPA and would harm Americans.

The EPA was established in the Nixon administration after the Love Canal environmental disaster, and was strengthened in the Reagan era. This supposedly non-partisan organization must rely on the best available research and minimal political interference to devise regulations that balance safety with vigorous commercial growth. When the EPA comes under political pressure, the consequences are severe, as when former EPA head Christie Whitman incorrectly testified about post-9/11 air quality in lower Manhattan. With the EPA responsible for regulations such as the Food Quality Protection Act, which in 1999 finally removed dangerous organophosphate pesticides from our food, political interference can cost lives.

The attention given lately to the challenges in repeating and extending results of research reported in individual published papers has given rise to new tools and practices to further strengthen the scientific endeavor. Over time, given the self-correcting nature of research, science uncovers the truth. While any single result may be difficult to reproduce, with evidence and consensus, novel claims are verified or refuted, and theories are confirmed or modified.

To be sure, there are countless ways to improve the research enterprise and to strengthen the rigor of individual research studies. Government agencies are in a position to play an effective role in encouraging these changes, but the EPAs proposed transparency rule does nothing of the sort.

Reducing the EPAs reliance on scientific knowledge will undermine science and have a catastrophic impact on the health of the country and its citizens.

Lenny Teytelman, Ph.D., is CEO of protocols.io in Berkeley, California. William Gunn, Ph.D., is director of scholarly communications at Elsevier. Joanne Kamens, Ph.D., is executive director of Addgene in Cambridge, Massachusetts.

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EPA's 'transparency rule' is bad for science and the environment - STAT

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