Category Archives: Molecular Genetics

Students and faculty gather at the University of Ottawa to memorialize four Ottawa students who died in the Tehran plane crash. Wayne Cuddington / Postmedia

The students who died this week in a plane crash near Tehran were poised to make their marks in the world of science, but they were also beloved friends and valued colleagues, said speakers at a memorial on Friday.

The four Ottawa students who perished in Wednesdays crash included University of Ottawa students Alma Oladi, a PhD student in mathematics with a specialty in genomics statistics, Saeed Kashani, a PhD student in chemistry, and Mehraban Badiei, a first-year student in health sciences, plus Fareed Arasteh, a Carleton University PhD student in molecular genetics who was married in Tehran only days before he boarded the ill-fateful flight.

Students and faculty members crowded the agora, a meeting place at the University of Ottawa, for a memorial that paid tearful tribute to the achievements and aspirations of the students as well as the roles they played in making their campuses more vibrant places. They spoke in English, French and Farsi.

As images of crash victims from across Canada flashed across a screen, some students broke into sobs and hugged each other. However, Carleton professor Askhan Golshani, who had been Arastehs academic advisor, urged the mourners to celebrate the lives of those who had been lost. All of these victims have made an impact, he said.

Students and faculty gathered at the University of Ottawa as the Iranian Student Association and Nowruz Student Association held a non-religious memorial ceremony to honour the three students who died in the tragic crash of Ukraine International Airlines Flight PS752 in Tehran this week.Wayne Cuddington / Postmedia

All 176 passengers and crew members were killed when Ukrainian International Airlines Flight 752 crashed shortly after taking off from the Tehran airport early Wednesday. Of those, 57 were Canadians, Foreign Affairs Minister Franois-Philippe Champagne said Friday, revising downward an earlier figure of 63 Canadians. Eight of the victims were Ottawa residents.

More than 50 of the crash victims were students at Canadian universities, University of Ottawa president Jacques Frmont told the memorial. He saluted the students commitment to making the world a better place.

Our hearts break for their families, their loved ones and their friends. We have come here today to mourn with you and offer our strength and our love at this terrible time, Frmont said. May their memories be blessed.

Badiei has only been at the University of Ottawa for a semester, but had already made an impact as a generous young woman who aspired to help those in need, said Lucie Thibault, the universitys dean of health sciences. Soon after arriving, Badiei joined a group supporting people with multiple sclerosis.

Mourners listen to speakers at a memorial for the four Ottawa university students who died in a plane crash in Iran on Wednesday.Wayne Cuddington / jpg

Kashani was determined to use his knowledge as a chemist to produce green products for a safer world. Friends recalled a young man who had been passionate about music and fitness. He had the innocence of a kid in his heart, one friend said.

Even though Kashani didnt care for Ottawas cold winters and muggy summers, after three years in the city he told friends he was finally ready to try skating on the Rideau Canal after returning from the winter break.

He was more than a coworker. He was a brother, one speaker said.

He always pushed people to live their lives to the fullest, another said. Lets learn from him. Lets be kind to one another. Life is unpredictable.

Students and faculty gathered at the University of Ottawa as the Iranian Student Association and Nowruz Student Association held a non-religious memorial ceremony to honour the three students who died in the tragic crash of Ukraine International Airlines Flight PS752 in Tehran this week.Wayne Cuddington / Postmedia

In an interview following the memorial, Golshani said international students who come to Canada are valuable in two ways. Those who who return to their countries become ambassadors for Canada, while those who chose to remain make significant contributions to research here. He estimates there are at least 20 faculty members of Iranian origin at Carleton.

Golshani recalls speaking to Arasteh about getting a PhD for the first time three years ago. It was something he really had to do, Golshani said.

It took Arasteh two years to get permission to join Golshanis lab. From the moment he came to Canada, he was hard at work, Golshani said.

Speaking at the memorial, Ottawa-Vanier MP Mona Fortier said young lives of promise and hope had been lost in the crash.

This is not a distant tragedy. These are losses to the Canadian family.

Full coverage of the Tehran plane crash

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'These are losses to the Canadian family': Mourners gather to remember students who died in Iran crash - Ottawa Citizen

A glance around the walls of Barry J. Byrnes office reveals a lot about the pediatric cardiologist who runs thePowell Gene Therapy Center at University of Florida (UF).

In one corner is an unusual painting by 9-year-old Will Barkowsky of Jacksonville, Fla. Will, the first boy with Duchenne muscular dystrophy to takeSarepta Therapeutics exon-skipping medication Exondys 51 (eteplirsen), put together his oil-on-canvas masterpiece using the tire tracks of his wheelchair, making sure the colors didnt mix.

Nearby is a movie poster for The Ataxian an award-winning 2015 documentary by Kevin Schlanser and Zack Bennett about 17-year-old Kyle Bryant, who despite having Friedreichs ataxia embarks on a cross-country bicycle trip with three buddies.

Another movie poster advertises Extraordinary Measures, the 2010 tearjerker starring Brendan Fraser as John Crowley the father of two kids with Pompe disease and later, the founder of Amicus Therapeutics and Harrison Ford as fictional researcher Robert Stonehill, who discovers a treatment for the genetic disorder that eventually saves the lives of Crowleys children.

Theres also a model of a Blalock-Taussig shunt frequently used in congenital heart surgery, as well as one of an adeno-associated virus (AAV) vector, along with a prominent photo of Byrne with Ron Bartek, co-founder and director of the Friedreichs Ataxia Research Alliance (FARA).

Friedreichs ataxia is where were putting most of our efforts now, said Byrne, who spoke to BioNews Services publisher of this website at length during a recent visit to his lab in Gainesville, Fla.

Byrne, along with Jerry Mendell, MD, a neurologist with Nationwide Childrens Hospital in Columbus, Ohio, hosted a Nov. 20 webinar on gene therapy organized by the National Organization for Rare Disorders (NORD) and the American Society for Gene & Cell Therapy.

The two experts were introduced by Katie Kowalski, senior program manager for NORDs Educational Initiatives. The webinar, Understanding the Gene Therapy Process and Aftercare, was the fourth in a five-part series underwritten by Amicus and Sarepta, as well as two other companies, Avrobio and Bluebird Bio.

The final webinar in the series, Life After Gene Therapy, is scheduled for Dec. 18.

Mendell, who heads Nationwides Center for Gene Therapy, specializes in gene therapy research for Duchenne as well as limb-girdle muscular dystrophy, spinal muscular atrophy (SMA) and X-linked myotubular myopathy. He was a principal investigator for the Novartis therapy Zolgensma, which uses an AAV vector to carry a working version of SMN1, the mutated gene in people with SMA.

Zolgensma won approval from the U.S. Food and Drug Administration (FDA) in May 2019 as the first gene therapy to treat SMA in infants up to 2 years of age.

At $2.125 million per patient, the hour-long Zolgensma infusion is the most expensive medicine in history. The cost easily eclipses that of the only other FDA-approved treatment for SMA, BiogensSpinraza(nusinersen), which retails for $750,000 the first year and $375,000 every year after.

Many of my colleagues have been trying to make inroads for years, Mendell said. When we first got into the gene therapy domain, we were limited by technology. We could not make enough virus for the kind of impact were having now. But technology has improved, and we can now deliver genes through circulation to reach all muscles.

Regardless of the disease, he said, its extremely important to confirm the patients specific mutation before anything else.

This is critical, because you dont want to deliver the wrong kind of gene in a disease like Friedreichs ataxia. That goes for all gene therapy trials, he said. Next, we want to check for pre-existing antibodies, whether theyre acquired from the environment or from close contact. They bind to the AAV and block entry to the target organ.

Checking for those antibodies requires a blood test. It generally takes 4-7 days to return lab results a nailbiting time for patients and families, Mendell said, because theyre waiting to be approved for enrollment in the trial.

Byrne estimated that 50-60% of all individuals may have been exposed to AAV.

Prior exposure at any level to any AAV infection is an exclusion in most studies, he said, noting that people who travel frequently or who have respiratory or gastrointestinal conditions are particularly susceptible. We are learning a lot about what thresholds are effective. Its about 10% of newborns and about 50% of those of school age and adulthood.

Patients must also be in general good health except, of course, for the genetic disease being treated. MRI and blood tests are done to rule out diabetes or any evidence of heart, liver, or kidney problems.

We put the patient to sleep so theres really no pain involved, Mendell said. We also use local numbing medicine, even though the patient is asleep, so theres no pain or discomfort.

The Powell Gene Therapy Center was established in 1996 the year before Byrne joined UF by Nicholas Muzyczka, PhD, who performed groundbreaking work on AAVs in the 1980s. The center has a dozen individual labs working in neuroscience and molecular genetics.

Byrne said that because gene therapy fundamentally changes many of the bodys cells, screening is crucial.

This is often a one-way street, in that since the effects are long-lasting, other experimental studies may not accept patients who have received gene therapy of any kind in the past, Byrne said. One must have the clinical features required of the study and meet certain functional and age criteria.

To prepare for screening, patients or their parents must read the informed consent and understand what the risks and benefits are. Genetic counseling also may be required to determine whether a given mutation is amenable to gene therapy.

Baseline evaluations are done when its a muscular skeletal disease timed function tests as well as lab tests and a study schedule is established, he said. In many of our studies, we see the patients very frequently, almost every day for the first two weeks. They stay in the area for up to a month. Because were often dealing with rare populations, that makes it convenient for us to evaluate these patients.

Byrne noted that gene therapy is not necessarily durable for the lifespan of the patient. Because the delivered gene does not integrate into the cells own DNA, it is not passed down to newly formed cells.

Some cells, particularly in the liver and muscle, continue to grow throughout childhood and AAV doesnt integrate, so its progressively less effective unless the cells being targeted, as in SMA, are not dividing, he said. Thats an example where newborn screening is critically important to better outcomes.

Mendell said he generally starts patients on prednisone one day before receiving gene therapy in order to suppress liver inflammation, and keeps them on it for 60 days after.

When were in the room, the first thing that happens is the gene is delivered. You push a button and get started, he said. Obviously it must be the correct gene. Its in there, but you cant see it.

The actual gene is delivered by intravenous (IV) infusion with a pump over a 90-minute period, Mendell said; anything faster than that could potentially cause harmful side effects.

We put IVs in both arms for continuous delivery in case one side gets clogged up. We dont want anything to stop gene delivery, he said. Meanwhile, the patient is constantly monitored for vital signs. We invite the whole family to stay together, and thats reassuring. Theres anxiety about gene therapy, but the potential benefits generally outweigh any risks involved.

Some patients may develop nausea and vomiting in the first one-to-three weeks following treatment. For this reason, blood is taken every two weeks for three months to check for side effects.

Mendell said he knows patients are responding to gene therapy by doing testing. In the case of Duchenne, he uses the North Star Ambulatory Assessment, which includes 17 timed tests such as climbing stairs, rising from a sitting position, and walking or running 100 meters. In addition, neck control is a very good indicator of efficacy among Duchenne boys, he said.

The FDA anticipates that within the next 10 years, it will approve up to 40 gene therapies for rare conditions. Mendell said the benefits of gene therapy for one condition in particular, SMA, are undeniable.

This is an absolutely devastating disease. In type 1 SMA, patients usually dont survive past age 2, and about 50% are gone by age 1, he said. Initially there was concern about giving this to infants, but we told the FDA we needed to test infants in order to save lives.

Continuing results from Mendells pivotal Phase 1 trial (NCT02122952) in 15 type 1 infants and along-term extension study (NCT03421977) have changed the way people view gene therapys potential in general.

After four years, he said, every patient in our trial went from being unable to sit to being able to, and several are able to walk. One patient was treated 28 days after birth, and now four years later, hes off to school. What Barry and I do is very gratifying, and we thank our patients and their families for this opportunity.

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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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Experts Barry Byrne, Jerry Mendell Lead NORD Webinar on Gene Therapy - SMA News Today

Twitter co-founder Jack Dorsey has created a lot of buzz over the years, but perhaps one of the biggest was when he admitted he only eats one meal per daywith longer breaks on the weekends (a practice known as intermittent fasting or OMAD), meditates twice per day, and uses a combination of sauna and ice baths at night (among other daily habits). The virality was swift, and fasting was even referred to as a Silicon Valley trend. It actually has another name, though, and that is biohacking. While tech guys certainly didnt invent biohacking, they have helped increase its visibility, leading a lot of people to wonder: What exactly is biohacking and should I be doing it?

Related: Everything You Need to Know About the Crazy-Sounding OMAD Diet Thats Trending Right Now

Oxford University Press defines biohacking in a shocking way: The activity of exploiting genetic material experimentally without regard to accepted ethical standards, or for criminal purposes. This harsh definition is hardly what Ive found in my research on the topic; while hacking and criminal are often synonymous in our minds, biohacking in its more extreme forms is hardly done with malicious intent (unless you think taking science and medicine out of the hands of big corporations with the hopes of making personal discoveries and breakthroughs is malicious).

Aside from that definition, there seem to be two camps on what biohacking exactly is. On the one hand you have the side that says biohacking is anything that changes the biology of your brain function. This includes many everyday pursuits such as nutrition, sleep habits and meditation (among others). However, there are others who believe biohacking is a deeper, more intentional do-it-yourself exploration of biology. Surprisingly, it doesnt always directly involve the body; for example, some biohackers seek to learn more about biology by engineering the genes in yeast.

Since the lines are blurry, were taking a look at both sides of biohacking and the science behind it. What you may find is that youve been biohacking your brain this whole time and didnt even know it.

You dont have to be in Silicon Valley using some never-heard-of technology and supplements to biohack your brain. Thats according to Karina Benameur, MD, an assistant professor in the Department of Neurology at Emory University, who teaches the open course Biohacking Your Brains Health and shares the view that biohacking can absolutely consists of really anything that enhances brain function.

A lot of people think biohacking is this high-tech thing, but it really doesnt have to be, she explains. Exercise is biohacking; nutrition is biohacking. What I go through in my course is how to biohack using things that are accessible to you in everyday life.

Benameurs main focus of study is nutrigenomics; specifically nutrition and its effect on neurological diseases. She notes that if you eat properly you can actually change the structure of your brain, making it a form of biohacking. In the same vein she specifically notes that meditation and exercise have been proven via magnetic resonance imaging (MRI) to have structural and functional changes in the brain.

Everything is interconnected; for you to change the structure of your brain, the nucleus of that neuron has to have expressed proteins to build more material for those areas to increase, Benameur explains. Anything that changes in the body has a correlate in the molecular genetic model; that is called epigenetic modification.

Thus lies the argument that biohacking is actually a broad process than just scientific experiments. For example, studies have been done that show aerobic activity has direct effects on the structure of the brain. Benameur notes that exercise increases certain neurotransmitters in the brain and that MRIs have confirmed it increase the size of your memory center. She admits that we often exercise to increase muscle mass and lose weight, but in fact, we are also unintentionally biohacking. While genetics are a consideration in our overall health and well-being, they can be changed through exercise, proper nutrition and more all because you are making an impact at the molecular level.

Related: Everyday Improvements You Can Make Right Now to Boost Your Brain Health and Extend Your Mindspan

Can biohacking really be that simple? According to Josiah Zayner, PhD, founder and CEO of The ODIN (and a biohacker himself), no; it is a technical discipline. Formerly a research scientist at NASA in their Synthetic Biology Program, Zayner left and founded The ODIN to make biohacking courses and kits available to the masses. Zayner believes that biohacking gives people the chance to directly contribute to science and medicine, in order to rely less on the scientific and medical systems already in place.

I want people to learn to be their own hope, because with million-dollar drug prices science and medicine are failing us, Zayner notes. F*** the scientific and medical systems that are killing us with opiates, taking 9 years on average to approve drugs and having the audacity to charge people to read and access scientific papers.

Zayner does the type of biohacking that probably comes to mind when you first hear the word; he has given himself a fecal transplant, experimented with various ways to genetically engineer his skin and even injected himself with DNA that underwent CRISPR gene-editing (which in part led to an investigation for practicing medicine without a license).

Zayner is far from the only person doing this type of experimentation, some extreme cases include one womana magicianwho had chips and magnets implanted in her body that are used during her shows (some by herself and some by a friend who is a nurse). There is also a man that has a chip implanted that can unlock his house. These examples dont directly involve changing the structure of the brain or DNA, but biohacking in this sense doesnt have to have that result. In fact, you can genetically engineer yeast to make your own glow-in-the-dark beer thanks to a kit Zayners company sells; youre still experimenting with biology and exploring a new fieldall from the comfort of your own home.

As biohacking is an ever-evolving field with different interpretations, how you biohack is up to you. Benameur speculates the practice is gaining popularity because of Silicon Valley. Other reasons include trendy new diets (take the rise of intermittent fasting popularized by celebrities including Jennifer AnistonandVanessa Hudgens) or simply the hope to stay young forever (like biohacker Eric Matzner).

People are always interested in making themselves better, she adds. They are curious about what they can do to make themselves better and if they can find shortcuts to do that, they will.

Even self-help guru Tony Robbinstouts biohacking as a means to take charge of improving your health. Of course, some biohacking practices involve a certain amount of risk, but it isnt just those that are seen as more extreme; this can even include trying to biohack your nutrition. Intermittent fasting, for example, is noted to carry the risk of eating too restrictively and also affecting cortisol levels (which impacts stress).

Zayner asks, Want to get started in biohacking? Its more simple that it seems, he shares. You can start by reading scientific journals. buying equipment, taking classes and exploring the science of the field in which you wish to understand.

Find out why Dr. Oz says the times you eat and take your medicine can significantly affect your health.

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Biohacking 101: What Does Biohacking Mean and Is It Safe? - Parade

The ability to fight disease is a driving force in human survival. Inflammation has emerged as a key weapon in this process. As pathogens change and evolve, the immune system adapts to keep up.

However, to what extent might such evolutionary adaptations also give rise to autoimmune conditions such as lupus and Crohn's disease?

This was a central question in a recent Trends in Immunology review by two scientists from Radboud University, in Nijmegen, Netherlands.

To address the issue, first author Jorge Domnguez-Andrs, a postdoctoral researcher in molecular life science, and senior author Prof. Mihai G. Netea, chair of experimental internal medicine, examined studies in the fields of virology, genetics, microbiology, and immunology.

They focused on people of African or Eurasian descent and how their ancestral origins may have influenced their risk of autoimmune diseases.

Of particular interest was how common pathogens in different communities related to changes in people's DNA, particularly when this involved inflammation.

The team found that the genetic changes made it harder for pathogen infections to take hold.

Over time, however, it seems that inflammation-related diseases, such as inflammatory bowel disease, Crohn's disease, and lupus, have emerged alongside improvements in immune defenses.

The findings also suggest that the human immune system continues to evolve and adapt to changes in environment and lifestyle.

"There seems to be a balance," says Domnguez-Andrs.

"Humans evolve to build defenses against diseases," he continues, "but we are not able to stop disease from happening, so the benefit we obtain on one hand also makes us more sensitive to new diseases on the other hand."

He observes that autoimmune diseases in today's humans tend to emerge later in life. These would not have caused health problems for our ancestors because their lives were much shorter.

"Now that we live so much longer," he explains, "we can see the consequences of infections that happened to our ancestors."

One of the examples that Domnguez-Andrs and Netea cover in detail in their review is malaria.

"Among various infectious diseases," they write, "malaria has exerted the highest evolutionary pressure on the communities across the African continent."

Malaria is a mosquito-borne disease that makes people very ill with flu-like symptoms, such as chills and a high fever.

While there has been much progress in the fight to control and eliminate the potentially fatal disease, it continues to threaten nearly half of the world's population, according to the World Health Organization (WHO).

The cause of malaria is parasites belonging to the species Plasmodium. These parasites spread to humans through the bites of infected female Anopheles mosquitoes.

Domnguez-Andrs and Netea note that Plasmodium has been infecting people in Africa for millions of years. During that period, the immune systems of those human populations have evolved stronger resistance to infection by increasing inflammation.

However, the downside of increasing inflammation to withstand infectious disease is that it favors health problems that tend to occur later in life.

Modern humans of African descent are more prone to developing such conditions, which include atherosclerosis and other cardiovascular diseases.

Another example of how ancestral changes in DNA leave imprints in the immune systems of modern humans is the interbreeding of early Eurasians with Neanderthals.

Modern humans whose genomes harbor remnants of Neanderthal DNA have immune systems that are better able to withstand staph infections and HIV-1. However, they are also more prone to asthma, hay fever, and other allergies.

Improvements in technology are making it more possible to find the downsides that can accompany disease-fighting adaptations.

Next generation sequencing, for example, is allowing scientists to delve more deeply into what happens at the DNA level between pathogens and the organisms that they infect.

Not only is new technology getting better at revealing genetic changes that occurred in our ancestors, but it is also showing that the human immune system continues to evolve and adapt.

In Africa, there are still tribes that hunt for food as their ancestors did. Thanks to new tools, scientists can see how the gut bacteria of these tribes are more diverse than those of, for example, contemporary African American people, who buy food in stores.

Other changes that have had an effect on DNA are the improvements in hygiene that have occurred in recent centuries. These have reduced exposure to pathogens and the diversity of gut bacteria.

"This reduced microbiota diversity in Western societies," the authors observe, "has been associated with a higher incidence of the so-called 'diseases of civilization,' such as cardiovascular diseases, diabetes, obesity, and autoimmune disorders, which are very unusual in hunter-gatherer societies, compared with communities living a Western-type lifestyle."

Domnguez-Andrs and Netea are extending their research to populations whose ancestry is other than African or Eurasian.

"Today, we are suffering or benefiting from defenses built into our DNA by our ancestors' immune systems fighting off infections or growing accustomed to new lifestyles."

Jorge Domnguez-Andrs, Ph.D.

Continued here:
Humans and autoimmune diseases continue to evolve together - Medical News Today

While robust market fundamentals point to a bright future for responsible aquaculture generally, in Norway massively improved biological material is paving the way for a rebound in cod farming in particular.

There has been very limited activity in cod production globally in recent years but that is about to change as pioneering aquaculture venture Norcod's plans to establish cod farming on an industrial scale gather momentum. Led by personnel with deep industry experience, Norcod is convinced that cod has the potential to be a significant contributor to the Norwegian economy. Quality biomass is the critical input factor.

Stemfish with poor biology and first-generation fry of inconsistent quality were partly to blame for the biomass loss seen during the last foray into cod farming between 2004 and 2012. Since then quantum leaps in biology have radically changed the landscape, with an estimated half-a-billion Norwegian kroner invested in two cod breeding programs that have been working quietly in the background in the belief that the tide would again turn.

Aquaculture-focused national research institute Nofima's breeding programme kicked off in 2002 with the goal to evolve economically important characteristics and disease resistance. Commercial hatchery player Havlandet Marin Yngel AS followed suit a year later. Their far-sighted commitment has seen the biological challenges of stagnant growth, susceptibility to infection and high escape figures systematically overcome.

Dramatically increased survival rate and quality of fry has been achieved through careful selection of eggs post fertilisation. The development of stemfish feed with minimal contamination has also boosted egg quality. Detailed comparative studies also showed that using eggs from four-year-old fish produce the best outcomes, according to Nofima.

Fish have been selected and developed for faster growth, higher harvest yield and higher resistance, while new feeds have been developed that support optimal growth and intestinal health. Farmed cod now grows up to 35 percent to 40 percent faster than fish in the wild.

Faster growth has always been the highest priority and has been the focus of the cod breeding programme. Breeding has led to a growth increase of 9 percent to 10 percent per generation, or around 3 percent per year about the same as for farmed salmon, says Atle Mortensen, senior scientist at Nofima.

Data from the stemfish produced for Norcod shows a dramatic 40 percent increase in survival rate for fish below 5 grams, up from 10 percent a decade ago. Successfully selecting for smaller heads has also been a game changer in boosting yield. In wild cod the much larger head can account for 40 percent of body weight.

Today's sixth generation of stem fish is a highly stable product and a completely different fish to 15 years ago, says Norcod managing director Rune Eriksen. Havlandet is now at capacity to deliver around three million fry, at 2-3 grams each, per annum. A kick-off batch of 260,000 fry from Nofima is already in production for Norcod and slated to go into the sea at the company's two facilities northwest of Trondheim imminently.

While growth was the holy grail, selecting specifically for other characteristics typically reduced the growth rate. Targeted breeding for disease resistance was unavoidable until the arrival of new and effective vaccines on the market. With these now available, the bacterial infections vibrosis and atypical furunculosis no longer pose a threat to farmed cod.

As per today there are no virus diseases that create problems for farmed cod. Both cod lice and sea lice affect cod but do not harm the fish like salmon lice do. Intestinal obstruction has very occasionally caused mortality in the sea phase. Compared to farmed salmon the health status of farmed cod is extremely good, says Mortensen.

The fish now show significant domestication, especially calm behaviour in the sea phase, swimming as a school in rings around the net much like salmon. That is astonishing given that selection was not made based on behaviour characteristics, says Mortensen. Not surprisingly, healthy, happy fish adapted to confinement grow faster. The high level of escape in the past was caused by the cod chewing holes in the nets. Today's tame fish display little desire to escape, while new standards and net technologies have also mitigated this tendency. Norcod's facilities are state of the art, optimising technical developments in equipment and feeding systems achieved in salmon farming in recent years.

Cannibalism is a peculiar trait of cod under stress but this problem has been virtually eradicated in the sixth generation of tame fish by means of improved feed and better feed distribution, allowing even growth across the population. Better growth, improved feed and optimal utilisation of feed also make it much easier to satisfy year-round demand.

Breeding has traditionally featured a combination of individual and family-based selection, with family selection ensuring diversity in the broodstock. The advent of molecular genetics, where information from the entire genome can be used for much greater precision in selecting for positive characteristics, promises even faster progress in the future.

Norcod stands to reap the rewards of these biological breakthroughs as a first mover. The quality of its cod is unmatched and unique globally. Initiating such a breeding project from scratch that could guarantee such strong characteristics would require a huge investment of time and money. But consumers want cod right now. Wild stocks are under pressure with limitations in capture quotas squeezing supply. Demand can only be met with cost-effective farming. Norcod's timing is on target to satisfy a market hungry for stable deliveries of fresh cod 12 months of the year.

Ensuring the welfare of the cod themselves throughout the production cycle also remains top priority. We should always remember that these are living creatures that should be handled with care and respect. No question, Eriksen says.

The production process from fry to plate takes between 23 to 26 months. Norcod has its sights set on sales of 9,000 tonnes of cod in 2021, rising to a total of 10 facilities with an output of 25,000 tonnes in 2025. We believe we have a very solid business case, says Eriksen. The market is waiting.

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Emerging science gives Norcod a path to further expansion - The Fish Site

Transparency Market Research (TMR) has published a new report titled Polymerase Chain Reaction (PCR) Consumables Global Industry Analysis, Size, Share, Growth, Trends, and Forecast, 20182026.According to the report, theglobal polymerase chain reaction (PCR) consumables marketwas valued at US$ 434 Mn in 2017 and is projected to expand at a CAGR of 4.8% from 2018 to 2026. The report suggests that increase in use of polymerase chain reaction consumables in quantification of plant mutations and genetically modified organisms, assessment of bacterial and viral loads and absolute pathogen counts, quantification of NGS libraries, and detection of cancer in body fluid and stool DNA are likely to drive the polymerase chain reaction consumables market from 2018 to 2026.

The molecular diagnostic industry has emerged as a major driver of development in PCR technology-based amplification techniques. The demand for greater efficiency and productivity in the pharmaceuticals industry has led to the growth of the polymerase chain reaction consumables market. PCR technologies have been used to identify and analyze potential drug targets due to the introduction of personalized medicine. Other major factors driving the polymerase chain reaction consumables market include enhanced automation, rise in demand for analysis technologies, research-intensive investment by various biotechnological companies, and wider application areas of PCR technologies.

The report offers detailed segmentation of the global polymerase chain reaction (PCR) consumables market based on product and end-user. In terms of product, the PCR tubes segment is anticipated to have high share due to high adoption of PCR tubes in research and academic institutes as well as clinical diagnostic laboratories and hospitals.

Research and Academic Institutesto Account for Major Share

The research and academic institutes segment is expected to account for a leading share of the market in 2026. The segment is also likely to expand at a rapid pace during the forecast period. PCR has become a functional tool in the mainstream life sciences and chemistry disciplines. Its applications range from molecular genetics to microbiology assays and are expanding beyond traditional areas. The clinical diagnostic labs and hospitals segment accounted for over 24.3% market share in 2017. The combination of exceptional specificity and sensitivity, low contamination risk, and low detection time has made PCR technology a better alternative to culture- or immunoassay-based testing methods for diagnosing various infectious diseases.

Request a PDF Brochure For Polymerase Chain Reaction (PCR) Consumables Market @https://www.transparencymarketresearch.com/sample/sample.php?flag=B&rep_id=43652

Market in Asia Pacific to Expand at a Significant Pace

North America held a prominent share of the global polymerase chain reaction (PCR) consumables market in 2017. The market has witnessed significant technological advancements, as companies have introduced newer PCR technologies and protocols. In addition, a large number of market players in the U.S. are focusing on R&D to introduce applications that would expand the use of PCR in new areas such as next-generation sequencing (NGS). Moreover, high awareness about latest health care technologies and higher purchasing power and affordability are anticipated to boost the PCR market in North America. Favorable reimbursement policies in the region also enable patients to avail of the best of health care facilities.

The polymerase chain reaction (PCR) consumables market in Asia Pacific is expected to expand at a rapid pace mainly due to improving health care infrastructure, rising private and public investment in life science research, and technological advancements in countries such as China and India. Less competition in Asia Pacific is encouraging a large number of instrument manufacturers to enter the market. QIAGEN established its Asia regional headquarters in Shanghai, China, in 2006. Presently, the company has a strong base in Asia Pacific, primarily in China, Singapore, Japan and India.

Key Players such as Den-Mat Holdings LLC, Valeant Pharmaceuticals International, Inc., and Dexcel Pharma to Lead the Market

The report also provides profiles of leading players operating in the global polymerase chain reaction (PCR) consumables market. They include Bio-Rad Laboratories, Inc., Hoffmann-La Roche Ltd., Inc., Thermo Fisher Scientific Inc., Qiagen N.V., Merck KGaA, Agilent Technologies, Inc., Eppendorf Group, 4titude, Corning Incorporated, and Greiner Bio-One International GmbH.

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Polymerase Chain Reaction (PCR) Consumables Market Research Explores The Key Success Factors, And Business Opportunities Including Key Players...

Expansions of DNA repeats are very hard to analyze. A method developed by researchers at the Max Planck Institute for Molecular Genetics in Berlin allows for a detailed look at these previously inaccessible regions of the genome. It combines nanopore sequencing, stem cell, and CRISPR-Cas technologies. The method could improve the diagnosis of various congenital diseases and cancers in the future.

Large parts of the genome consist of monotonous regions where short sections of the genome repeat hundreds or thousands of times. But expansions of these "DNA repeats" in the wrong places can have dramatic consequences, like in patients with Fragile X syndrome, one of the most commonly identifiable hereditary causes of cognitive disability in humans. However, these repetitive regions are still regarded as an unknown territory that cannot be examined appropriately, even with modern methods.

A research team led by Franz-Josef Mller at the Max Planck Institute for Molecular Genetics in Berlin and the University Hospital of Schleswig-Holstein in Kiel recently shed light on this inaccessible region of the genome. Mller's team was the first to successfully determine the length of genomic tandem repeats in patient-derived stem cell cultures. The researchers additionally obtained data on the epigenetic state of the repeats by scanning individual DNA molecules. The method, which is based on nanopore sequencing and CRISPR-Cas technologies, opens the door for research into repetitive genomic regions, and the rapid and accurate diagnosis of a range of diseases.A gene defect on the X chromosomeIn Fragile X syndrome, a repeat sequence has expanded in a gene called FMR1 on the X chromosome. "The cell recognizes the repetitive region and switches it off by attaching methyl groups to the DNA," says Mller. These small chemical changes have an epigenetic effect because they leave the underlying genetic information intact. "Unfortunately, the epigenetic marks spread over to the entire gene, which is then completely shut down," explains Mller. The gene is known to be essential for normal brain development. He states: "Without the FMR1 gene, we see severe delays in development leading to varying degrees of intellectual disability or autism."

Female individuals are, in most cases, less affected by the disease, since the repeat region is usually located on only one of the two X chromosomes. Since the unchanged second copy of the gene is not epigenetically altered, it is able to compensate for the genetic defect. In contrast, males have only one X chromosome and one copy of the affected gene and display the full range of clinical symptoms. The syndrome is one of about 30 diseases that are caused by expanding short tandem repeats.

First precise mapping of short tandem repeats

In this study, Mller and his team investigated the genome of stem cells that were derived from patient tissue. They were able to determine the length of the repeat regions and their epigenetic signature, a feat that had not been possible with conventional sequencing methods. The researchers also discovered that the length of the repetitive region could vary to a large degree, even among the cells of a single patient.

The researchers also tested their process with cells derived from patients that contained an expanded repeat in one of the two copies of the C9orf72 gene. This mutation leads to one of the most common monogenic causes of frontotemporal dementia and amyotrophic lateral sclerosis. "We were the first to map the entire epigenetics of extended and unchanged repeat regions in a single experiment," says Mller. Furthermore, the region of interest on the DNA molecule remained physically wholly unaltered. "We developed a unique method for the analysis of single molecules and for the darkest regions of our genome - that's what makes this so exciting for me."

Tiny pores scan single molecules

"Conventional methods are limited when it comes to highly repetitive DNA sequences. Not to mention the inability to simultaneously detect the epigenetic properties of repeats," says Bjrn Brndl, one of the first authors of the publication. That's why the scientists used Nanopore sequencing technology, which is capable of analyzing these regions. The DNA is fragmented, and each strand is threaded through one of a hundred tiny holes ("nanopores") on a silicon chip. At the same time, electrically charged particles flow through the pores and generate a current. When a DNA molecule moves through one of these pores, the current varies depending on the chemical properties of the DNA. These fluctuations of the electrical signal are enough for the computer to reconstruct the genetic sequence and the epigenetic chemical labels. This process takes place at each pore and, thus, each strand of DNA.

Genome editing tools and bioinformatics illuminate "dark matter"Conventional sequencing methods analyze the entire genome of a patient. Now, the scientists designed a process to look at specific regions selectively. Brndl used the CRISPR-Cas system to cut DNA segments from the genome that contained the repeat region. These segments went through a few intermediate processing steps and were then funneled into the pores on the sequencing chip.

"If we had not pre-sorted the molecules in this way, their signal would have been drowned in the noise of the rest of the genome," says bioinformatician Pay Giesselmann. He had to develop an algorithm specifically for the interpretation of the electrical signals generated by the repeats: "Most algorithms fail because they do not expect the regular patterns of repetitive sequences." While Giesselmann's program "STRique" does not determine the genetic sequence itself, it counts the number of sequence repetitions with high precision. The program is freely available on the internet.

Numerous potential applications in research and the clinic"With the CRISPR-Cas system and our algorithms, we can scrutinize any section of the genome - especially those regions that are particularly difficult to examine using conventional methods," says Mller, who is heading the project. "We created the tools that enable every researcher to explore the dark matter of the genome," says Mller. He sees great potential for basic research. "There is evidence that the repeats grow during the development of the nervous system, and we would like to take a closer look at this."

The physician also envisions numerous applications in clinical diagnostics. After all, repetitive regions are involved in the development of cancer, and the new method is relatively inexpensive and fast. Mller is determined to take the procedure to the next level: "We are very close to clinical application."

Reference: Giesselmann et al. 2019.Analysis of short tandem repeat expansions and their methylation state with nanopore sequencing. Nature Biotechnology.DOI: https://doi.org/10.1038/s41587-019-0293-x.

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New Device Permits a Closer Look at Previously Inaccessible Areas of the Genome - Technology Networks

Salmonella is acting up in Michigan, and it could be a model for whats happening in other states, according to a new Michigan State University study.

The study, appearing in Frontiers in Medicine, documents a substantial uptick in antibiotic resistant strains, and consequently, longer hospital stays as doctors work to treat the increasing virulent pathogens.

If you get a salmonella infection that is resistant to antibiotics today, you are more likely to be hospitalized longer, and it will take you longer to recover, said Shannon Manning, MSU Foundation professor in theDepartment of Microbiology and Molecular Genetics and senior author of the study. We need better detection methods at the clinical level to identify resistant pathogens earlier so we can treat them with the right drugs the first time.

Losing a day or more to misdiagnosis or improper treatment allows symptoms to get worse. Doctors might kill off a subpopulation of bacteria that are susceptible, but the ones that are resistant grow stronger, she added.

Salmonella is a diverse group of bacterial pathogens that causes foodborne infections. Infected patients often develop diarrhea, nausea, vomiting and abdominal pain, though some infections are more severe and can be life threatening.

When it comes to treatments, each strain reacts differently to the range of antibiotics available for prescription by doctors. So getting it right the first time is crucial.

Specifically in Michigan, doctors are seeing more strains that are resistant to ampicillin, a common antibiotic prescribed to treat salmonella. Multidrug resistance, or resistance to more than three classes of antibiotics, has also increased in Michigan and could further complicate patient treatment plans.

Were still uncertain as to why this is happening; it could be that these antibiotics have been overprescribed in human and veterinary medicine and that possessing genes for resistance has allowed these bacteria to grow and thrive in the presence of antibiotics, Manning said. Each state has its own antibiotic-resistance issues. Its important that the medical profession remains vigilant to ever-changing patterns of resistance in salmonella and other foodborne pathogens, rather than look for a blanket national solution.

Historically, salmonella has affected young children and the elderly, but now theres been a rise in adult cases, suggesting that the epidemiology of the infections has changed in Michigan.

Diving into individual strains of salmonella, the team of scientists found that patients with Typhimurium were more likely to have resistant infections as were patients infected during the fall, winter or spring months.

Another distinction was revealed between the strains affecting people living in rural and urban areas. Enteritis infections tend to be higher in rural areas. This may be attributed to rural residents exposure to farm animals or untreated sources of water.

Each states salmonella population has its own personality; so every states approach to identifying disease drivers and effective treatments should be modified to reflect these traits.

Our results show the importance of surveillance, monitoring resistance frequencies and identifying risk factors specific to each state and region, Manning said. The trends that are revealed can lead to new prevention strategies.

Additional MSU researchers contributing to the study include Sanjana Mukherjee, the lead author, Chase Anderson and Rebekah Mosci. Scientists from Wayne State, Sparrow Hospitals and the Michigan Department of Health and Human Services also contributed to this research.

(Note for media: Please include a link to the original paper in online coverage: https://www.frontiersin.org/articles/10.3389/fmed.2019.00250/full)

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The nature of salmonella is changing and it's meaner - MSUToday

Fifty-two faculty members and researchers at the University of California San Diego are among the worlds most influential in their fields. The Web of Science Group, an information and technology provider for the global scientific research community, compiled its2019 Highly Cited Researcherslist of more than 6,000 scientists from around the world whose studies were among the top 1% of most-cited publications in their field over the past 11 years.

The number of highly cited researchers from UC San Diego increased by 13% over last years number of forty-six. The listing covers 21 fields of study as well as a cross-field category for researchers who are widely cited across multiple fields. UC San Diego had researchers listed in 14 fields, with the most cited in cross-field (23), followed by molecular biology and genetics (5), clinical medicine (4) and social sciences (4).

UC San Diego has some of the most dedicated, brilliant and hard-working faculty and researchers in the world. Their inclusion on the list of highly cited researchers is a measure of their impact in their respective fields of study as they continue to advance the frontiers of knowledge, said Chancellor Pradeep K. Khosla.

Of particular note is Director for the Center of Microbiome Innovation Rob Knights inclusion in three separate areas of study (biology and biochemistry, environment and ecology, microbiology). Out of 6,216 highly cited researchers, only 11 were cited in three fields, making Knight part of a super elite 0.3% of those listed.

There were also 23 Nobel laureates on the list, one of whom, Roger Tsien, was a distinguished professor of both Pharmacology in the School of Medicine and of Chemistry and Biochemistry at UC San Diego until his death in 2016. He shared the Nobel Prize in Chemistry with two others in 2008 for discovering and developing green fluorescent protein.

David Pendlebury, Senior Citation Analyst at the Web of Science Groups Institute for Scientific Information said that the highly cited researchers create gains for society, innovation and knowledge that make the world healthier, richer, more sustainable and more secure.

It is especially encouraging to see not only the number of highly cited researchers at the university, but the broad range of fields in which they are cited. It really speaks to the fact that UC San Diego conducts groundbreaking research across a wide range of disciplines, said Vice Chancellor for Research Sandra A. Brown. I congratulate everyone on their excellent research and contributions.

The 52 UC San Diego faculty members named by Web of Science and the fields of study in which they were cited are:

Gregory Aarons,social sciences

Ludmil Alexandrov, molecular biology and genetics

David Brenner,cross-field

Kristin Cadenhead,psychiatry/psychology

Kelli Cain, social sciences

Shu Chien, cross-field

Don Cleveland,neuroscience and behavior

Seth Cohen,chemistry

Pieter Dorrestein,cross-field

Mark Ellisman, cross-field

Mark Estelle,plant and animal science

Michael Folger, cross-field

Anthony Gamst, cross-field

Christopher Glass,molecular biology and genetics

Uri Gneezy,economics and business

Antonio Gonzalez, microbiology

Kun-Liang Guan,molecular biology and genetics

Trey Ideker,cross-field

Michael Karin,molecular biology and genetics

Arthur Kavanaugh,clinical medicine

Dusan Keres, space science

Rob Knight,(listed in 3 fields) biology and biochemistry, environment and ecology, microbiology

Razelle Kurzrock, clinical medicine

Lisa Levin, cross-field

Irene Litvan, neuroscience and behavior

Rohit Loomba, clinical medicine

Prashant Mali, biology and biochemistry

Eliezer Masliah, cross-field

Victor Nizet, cross-field

Jerrold Olefsky,cross-field

Bernhard Palsson,biology and biochemistry

Veerabhadran Ramanathan,cross-field

Bing Ren,molecular biology and genetics

Jeremy Rich, cross-field

Douglas Richman,cross-field

Michael Sailor,cross-field

James Sallis,social sciences

William Sandborn,clinical medicine

Bernd Schnabl, cross-field

Julian Schroeder,plant and animal science

Terrence Sejnowski, cross-field

Claude Sirlin, cross-field

Murray Stein,psychiatry/psychology

Steffanie Strathdee, cross-field

Roger Tsien, cross-field

Ming Tsuang,psychiatry/psychology

Joseph Wang,chemistry

Shang-Ping Xie,geosciences

Gene Yeo, cross-field

Kun Zhang, cross-field

Liangfang Zhang,cross-field

Yunde Zhao, plant and animal science

Shu-Hong Zhu, social sciences

You can read about Web of Sciences methodology on their website.

UC San Diegos Studio Ten 300 offers radio and television connections for media interviews with our faculty. For more information, email .(JavaScript must be enabled to view this email address).

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A thousand seemingly insignificant things change as an organism ages. Beyond the obvious signs like graying hair and memory problems are myriad shifts both subtler andmore consequential: Metabolic processes run less smoothly; neurons respond less swiftly; the replication of DNA grows faultier.

But while bodies mayseem to just gradually wear out, many researchers believe instead that aging is controlled at the cellular and biochemical level. They find evidence for this in the throngof biological mechanisms that are linked to aging but also conserved across species as distantly related as roundworms and humans. Whole subfields of research have grown up around biologists attempts to understand the relationships among the core genes involved in aging, which seem to connect highly disparate biological functions, like metabolism and perception. If scientists can pinpoint which of the changes in these processes induce aging, rather than result from it, it may be possible to intervene and extend the human life span.

So far, research has suggested that severely limiting calorie intake can have a beneficial effect, as can manipulating certain genes in laboratory animals. But recently in Nature, Bruce Yankner, a professor of genetics and neurology at Harvard Medical School, and his colleagues reported on a previously overlooked controller of life span: the activity level of neurons in the brain. In a series of experiments on roundworms, mice and human brain tissue, they found that a protein called REST, which controls the expression of many genes related to neural firing, also controls life span. They also showed that boosting the levels of the equivalent of REST in worms lengthens their lives by making their neurons fire more quietly and with more control. How exactly overexcitation of neurons might shorten life span remains to be seen, but the effect is real and its discovery suggests new avenues for understanding the aging process.

In the early days of the molecular study of aging, many people were skeptical that it was even worth looking into. Cynthia Kenyon, a pioneering researcher in this area at the University of California, San Francisco, has described attitudes in the late 1980s: The ageing field at the time was considered a backwater by many molecular biologists, and the students were not interested, or were even repelled by the idea. Many of my faculty colleagues felt the same way. One told me that I would fall off the edge of the Earth if I studied ageing.

That was because many scientists thought that aging (more specifically, growing old) must be a fairly boring, passive process at the molecular level nothing more than the natural result of things wearing out. Evolutionary biologists argued that aging could not be regulated by any complex or evolved mechanism because it occurs after the age of reproduction, when natural selection no longer has a chance to act. However, Kenyon and a handful of colleagues thought that if the processes involved in aging were connected to processes that acted earlier in an organisms lifetime, the real story might be more interesting than people realized. Through careful, often poorly funded work on Caenorhabditis elegans, the laboratory roundworm, they laid the groundwork for what is now a bustling field.

A key early finding was that the inactivation of a gene called daf-2 was fundamental to extending the life span of the worms. daf-2 mutants were the most amazing things I had ever seen. They were active and healthy and they lived more than twice as long as normal, Kenyon wrote in a reflection on these experiments. It seemed magical but also a little creepy: they should have been dead, but there they were, moving around.

This gene and a second one called daf-16 are both involved in producing these effects in worms. And as scientists came to understand the genes activities, it became increasingly clear that aging is not separate from the processes that control an organisms development before the age of sexual maturity; it makes use of the same biochemical machinery. These genes are important in early life, helping the worms to resist stressful conditions during their youth. As the worms age, modulation of daf-2 and daf-16 then influences their health and longevity.

These startling results helped draw attention to the field, and over the next two decades many other discoveries illuminated a mysterious network of signal transduction pathways where one protein binds another protein, which activates another, which switches off another and so on that, if disturbed, can fundamentally alter life span. By 1997, researchers had discovered that in worms daf-2 is part of a family of receptors that send signals triggered by insulin, the hormone that controls blood sugar, and the structurally similar hormone IGF-1, insulin-like growth factor 1; daf-16 was farther down that same chain. Tracing the equivalent pathway in mammals, scientists found that it led to a protein called FoxO, which binds to the DNA in the nucleus, turning a shadowy army of genes on and off.

That it all comes down to the regulation of genes is perhaps not surprising, but it suggests that the processes that control aging and life span are vastly complex, acting on many systems at once in ways that may be hard to pick apart. But sometimes, its possible to shine a little light on whats happening, as in the Yankner groups new paper.

Figuring out which genes are turned on and off in aging brains has long been one of Yankners interests. About 15 years ago, in a paper published in Nature, he and his colleagues looked at gene expression data from donated human brains to see how it changes over a lifetime. Some years later, they realized that many of the changes theyd seen were caused by a protein called REST. REST, which turns genes off, was mainly known for its role in the development of the fetal brain: It represses neuronal genes until the young brain is ready for them to be expressed.

But thats not the only time its active. We discovered in 2014 that [the REST gene] is actually reactivated in the aging brain, Yankner said.

To understand how the REST protein does its job, imagine that the network of neurons in the brain is engaged in something like the party game Telephone. Each neuron is covered with proteins and molecular channels that enable it to fire and pass messages. When one neuron fires, it releases a flood of neurotransmitters that excite or inhibit the firing of the next neuron down the line. REST inhibits the production of some of the proteins and channels involved in this process, reining in the excitation.

In their new study, Yankner and his colleagues report that the brains of long-lived humans have unusually low levels of proteins involved in excitation, at least in comparison with the brains of people who died much younger. This finding suggests that the exceptionally old people probably had less neural firing. To investigate this association in more detail, Yankners team turned to C. elegans. They compared neural activity in the splendidly long-lived daf-2 mutants with that of normal worms and saw that firing levels in the daf-2 animals were indeed very different.

They were almost silent. They had very low neural activity compared to normal worms, Yankner said, noting that neural activity usually increases with age in worms. This was very interesting, and sort of parallels the gene expression pattern we saw in the extremely old humans.

When the researchers gave normal roundworms drugs that suppressed excitation, it extended their life spans. Genetic manipulation that suppressed inhibition the process that keeps neurons from firing did the reverse. Several other experiments using different methods confirmed their results. The firing itself was somehow controlling life span and in this case, less firing meant more longevity.

Because REST was plentiful in the brains of long-lived people, the researchers wondered if lab animals without REST would have more neural firing and shorter lives. Sure enough, they found that the brains of elderly mice in which the Rest gene had been knocked out were a mess of overexcited neurons, with a tendency toward bursts of activity resembling seizures. Worms with boosted levels of their version of REST (proteins named SPR-3 and SPR-4) had more controlled neural activity and lived longer. But daf-2 mutant worms deprived of REST were stripped of their longevity.

It suggests that there is a conserved mechanism from worms to [humans], Yankner said. You have this master transcription factor that keeps the brain at what we call a homeostatic or equilibrium level it doesnt let it get too excitable and that prolongs life span. When that gets out of whack, its deleterious physiologically.

Whats more, Yankner and his colleagues found that in worms the life extension effect depended on a very familiar bit of DNA: daf-16. This meant that RESTs trail had led the researchers back to that highly important aging pathway, as well as the insulin/IGF-1 system. That really puts the REST transcription factor somehow squarely into this insulin signaling cascade, said Thomas Flatt, an evolutionary biologist at the University of Fribourg who studies aging and the immune system. REST appears to be yet another way of feeding the basic molecular activities of the body into the metabolic pathway.

Neural activity has been implicated in life span before, notes Joy Alcedo, a molecular geneticist at Wayne State University who studies the connections between sensory neurons, aging and developmental processes. Previous studies have found that manipulating the activity of even single neurons in C. elegans can extend or shorten life span. Its not yet clear why, but one possibility is that the way the worms respond biochemically to their environment may somehow trip a switch in their hormonal signaling that affects how long they live.

The new study, however, suggests something broader: that overactivity in general is unhealthy. Neuronal overactivity may not feel like anything in particular from the viewpoint of the worm, mouse or human, unless it gets bad enough to provoke seizures. But perhaps over time it may damage neurons.

The new work also ties into the idea that aging may fundamentally involve a loss of biological stability, Flatt said. A lot of things in aging and life span somehow have to do with homeostasis. Things are being maintained in a proper balance, if you will. Theres a growing consensus in aging research that what we perceive as the body slowing down may in fact be a failure to preserve various equilibria. Flatt has found that aging flies show higher levels of immune-related molecules, and that this rise contributes to their deaths. Keeping the levels in check, closer to what they might have been when the flies were younger, extends their lives.

The results may help explain the observation that some drugs used for epilepsy extend life span in lab animals, said Nektarios Tavernarakis, a molecular biologist at the University of Crete who wrote a commentary that accompanied Yankners recent paper. If overexcitation shortens life span, then medicines that systematically reduce excitation could have the opposite effect. This new study provides a mechanism, he said.

In 2014, Yankners laboratory also reported that patients with neurodegenerative diseases like Alzheimers have lower levels of REST. The early stages of Alzheimers, Yankner notes, involve an increase in neural firing in the hippocampus, a part of the brain that deals with memory. He and his colleagues wonder whether the lack of REST contributes to the development of these diseases; they are now searching for potential drugs that boost REST levels to test in lab organisms and eventually patients.

In the meantime, however, its not clear that people can do anything to put the new findings about REST to work in extending their longevity. According to Yankner, REST levels in the brain havent been tied to any particular moods or states of intellectual activity. It would be a misconception, he explained by email, to correlate amount of thinking with life span. And while he notes that there is evidence that meditation and yoga can have a variety of beneficial effects for mental and physical health, no studies show that they have any bearing on REST levels.

Why exactly do overexcited neurons lead to death? Thats still a mystery. The answer probably lies somewhere downstream of the DAF-16 protein and FoxO, in the genes they turn on and off. They may be increasing the organisms ability to deal with stress, reworking its energy production to be more efficient, shifting its metabolism into another gear, or performing any number of other changes that together add up a sturdier and longer-lived organism. It is intriguing that something as transient as the activity state of a neural circuit could have such a major physiological influence on something as protean as life span, Yankner said.

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Longevity Linked to Proteins That Calm Overexcited Neurons - Quanta Magazine