Monthly Archives: February 2017

Molecular hairpin structures make effective DNA replicators – Phys.Org

Posted: February 17, 2017 at 12:51 am

February 16, 2017 Credit: rost9 / fotolia.com

The evolution of cells and organisms is thought to have been preceded by a phase in which informational molecules like DNA could be replicated selectively. New work shows that hairpin structures make particularly effective DNA replicators.

In the metabolism of all living organisms there is a clear division of labor: Nucleic acids (DNA and RNA) carry the information for the synthesis of proteins, and proteins provide the structural and executive functions required by cells, such as the controlled and specific catalysis of chemical reactions by enzymes. However, in recent decades, it has become clear that this distinction is by no means absolute. In particular RNA is capable of ignoring the boundary outlined above and is known to play a catalytic role in many important processes. For example, certain RNA molecules can catalyze the replication of other nucleic acids, and this versatility could help to explain how life originated on Earth.

Nucleic acid molecules are made up of subunits called nucleotides, which differ in their so-called bases. The bases found in RNA are referred to as A, C, G and U (DNA uses T in place of U). These bases fall into two complementary pairs, whose members specifically interact, A with T (or U) and G with C. This complementarity is what accounts for the stability of the DNA double helix, and enables single strands of RNA to fold into complex shapes.

Life is thought to have emerged from a process of chemical evolution in which nucleic acid sequences could be selectively replicated. Thus, in prebiotic systems certain molecular "species" that carried information were reproduced at the expense of others. In biological systems, such selectivity is normally mediated by so-called primersstrands of nucleic acid that pair (as described above) with part of the molecule to be replicated, to form a short double helix. The primer provides a starting point for the extension of the double-stranded region to form a new daughter strand. Moreover, this process can be reconstructed in the test-tube.

The pros and cons of hairpin replicators

Georg Urtel and Thomas Rind, who are members of the research group led by Dieter Braun (Professor of Systems Biophysics at LMU), have used such a system to identify properties the might favor the selective replication of DNA molecules. For their experiments, they chose a single-stranded DNA sequence that adopts a so-called hairpin structure. In these molecules, the base sequences at either end are complementary to each other, as are short stretches of sequence within the rest of the molecule. This distribution of complementary sequences causes such a strand to fold into a hairpin-like conformation.

Thanks to the pairing rules outlined above, replication of a single strand of DNA produces a second strand whose sequence differs from that of the first. Each strand of a non-hairpin structure therefore needs its own primer for replication. But with hairpins, one primer suffices to prime synthesis of both the original and its complementary strand. "This means that hairpins are relatively simple replicators," Georg Urtel points out. The downside is that the hairpin structure makes primer binding more difficult, and this in turn limits their replication rate. Molecular species that are devoid of hairpin structures don't have this problem.

Cooperation beats competition

In subsequent experiments the researchers discovered that two simple hairpin species could cooperate to give rise to a much more efficient replicator, which requires two primers for its amplification. The two hairpin species selected each required a different primer, but their sequences were in part identical. The switch to cooperative replication occurs when replication of one of the hairpins stalls. "As a rule, replication processes in nature are never perfect," says Dieter Braun. "Such a premature halt is not something that one needs to design into the system. It happens stochastically and we make use of it in our experiments." The partially replicated hairpin can, however, bind to a molecule of the second species, and serves as a primer that can be further elongated. Moreover, the resulting product no longer forms a hairpin. In other words, it represents a new molecular species.

Saved from extinction

Such so-called 'crossbreeds' need two primers for their replication, but can nevertheless be replicated significantly faster than either of their hairpin progenitors For further experiments showed that, upon serial dilution of the population, the hairpin DNAs soon become extinct. However, the sequence information they contained survives in the crossbreeds and can be replicated further.

The converse experiment confirmed that information is indeed conserved: If crossbreeds are supplied with only one primer, the corresponding progenitor hairpin species can still be replicated by the kind of switching process mentioned above. But, in the absence of the second primer, the crossbreed dies out. "Thus, the crossbreeding process not only provides for the transition from 'simple and slow' replicators to more rapid replicators, it also makes it possible for the system to adapt to the prevailing conditions," Urtel explains. "It also suggests how early replicators could have cooperated with each other under prebiotic conditions prior to the origin of living systems."

Explore further: Genetic switch regulates transcription and replication in human mitochondria

More information: Georg C. Urtel et al. Reversible Switching of Cooperating Replicators, Physical Review Letters (2017). DOI: 10.1103/PhysRevLett.118.078102

(Phys.org)The majority of the human genome is located within the nucleus. However, there is a small but important portion of DNA located within the mitochondria. This mitochondrial DNA (mtDNA) has received much attention ...

Researchers at Case Western Reserve University and the University of Michigan have produced the first image of an important human protein as it binds with ribonucleic acid (RNA), a discovery that could offer clues to how ...

MIT scientists have found a new way that DNA can carry out its work that is about as surprising as discovering that a mold used to cast a metal tool can also serve as a tool itself, with two complementary shapes each showing ...

DNA lesions are really common about one million individual molecular lesions per cell per day because its long strands usually have one missing base or are damaged. These lesions can stall the DNA replication process, ...

The original recipe for gene soup may have been simplerain, a jumble of common molecules, warm sunshine, and nighttime cooling. Then add a pinch of thickener.

UV light damages DNA. But LMU researchers now show that it can also mediate non-enzymatic repair of one type of damage, albeit in a specific context. This effect may have played vital role in early evolution of living systems.

Research led by ANU on the use of magnets to steer light has opened the door to new communications systems which could be smaller, cheaper and more agile than fibre optics.

University of Toronto (U of T) researchers have demonstrated a way to increase the resolution of microscopes and telescopes beyond long-accepted limitations by tapping into previously neglected properties of light. The method ...

The demand for faster computers is growing rapidly and the rise of big data demands novel solutions be explored to deliver quicker results.

Although scientists have been able to levitate specific types of material, a pair of UChicago undergraduate physics students helped take the science to a new level.

Experiments at ANSTO have provided supporting evidence of unexpected enhancement of water solubility of biomolecules in an aqueous solution of divalent transition-metal cations.

A detection device designed and built at Yale is narrowing the search for dark matter in the form of axions, a theorized subatomic particle that may make up as much as 80% of the matter in the universe.

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Molecular hairpin structures make effective DNA replicators - Phys.Org

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Tumor mutation or DNA damage? New study calls genomic workflows into question – MedCity News

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MedCity News
Tumor mutation or DNA damage? New study calls genomic workflows into question
MedCity News
There are well-known limitations when it comes to sequencing old or previously frozen DNA samples. Damage inevitably occurs with age, handling and storage, decreasing the accuracy and sensitivity of the sequencing data. Fresh, high-quality samples, on ...
New England Biolabs Study Highlights Extent of DNA Damage in Samples, Resulting Sequencing ErrorsGenomeWeb

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Transient charged after DNA on shoelace links him to Marymoor … – The Seattle Times

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When the victim asked the defendant why he was doing this, he responded he had to do it and that he was going to kill her, according to charging papers filed in King County Superior Court.

DNA found on a shoelace used to choke a woman who was viciously beaten in Redmonds Marymoor Park in August has been matched to a 33-year-old transient who is a patient at a state mental hospital after an unrelated crime, according to King County prosecutors.

Charles Stockwell Jr. was charged Wednesday with first-degree assault in connection with the Aug. 5 attack on a 43-year-old Redmond woman who was walking her dog in the park.

Stockwell is accused of hiding out in bushes, then attacking the victim from behind. He threw her to the ground next to the trail and immediately began punching her in the face and head, and pushing his thumbs into her throat, according to charging papers.

When the victim asked the defendant why he was doing this, he responded he had to do it and that he was going to kill her. At that moment, the victim thought she was going to die, Senior Deputy Prosecutor William Doyle wrote in charging papers.

As the victim tried to fight back, Stockwell grabbed her arm and wrenched it behind her, causing her elbow to pop out of its socket, the charges say.

With the victim screaming on the ground in pain, the defendant took a shoelace out of one of his shoes, put it around the victims neck, and began strangling her with it, Doyle wrote.

As the woman began to lose consciousness, she used her fingers to pull the shoelace from her neck and screamed for help. A man walking in the area heard her screams, ran over and scared the attacker away, the charges say. The attacker fled, leaving behind a pair of white tennis shoes.

That night, a King County sheriffs sergeant went to Overlake Medical Center to interview the woman, who was being treated for her injuries, the papers say. During her medical exam, the shoelace was found in her hair.

The victim met with a police sketch artist, who came up with a sketch of the suspect, the charges say.

The victims DNA was found on the shoelace along with DNA from at least two others, but no matches were found.

Then in December, during a routine scheduled search, the DNA from the shoelace was run through the Combined DNA Index System (CODIS), a database of DNA profiles, and hit on Stockwell, the charges say.

Detectives learned Stockwell was in the Thurston County Jail after his arrest in connection with a residential burglary in Tumwater three days after the Marymoor Park attack, say the charges.

Detectives met with Stockwells parents, who said their son had been injured while working as a tree trimmer, then got addicted to pain pills before moving on to heroin and methamphetamine, the charges say. His mother told detectives Stockwell has a violent temper and both parents are afraid of him, say the charges.

The parents said Stockwell had shown up at their house the day before the Marymoor Park attack and his father gave him a pair of white tennis shoes, according to the charges. The father then drove Stockwell to the Port Orchard ferry and told detectives his son had then planned to take the Bremerton ferry to Seattle.

Stockwell called his parents on Aug. 8 from the Thurston County Jail, but they refused to bail him out, the charges say.

In September, Stockwell was sent to Western State Hospital for a competency evaluation and was found not competent to stand trial. In December, he was sent back to the hospital, where he remains.

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Transient charged after DNA on shoelace links him to Marymoor ... - The Seattle Times

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How Silicon Valley Is Trying to Hack Its Way Into a Longer Life – TIME

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Isabella Connelley and Bethan Mooney for TIMEIsabella Connelley and Bethan Mooney for TIME

The titans of the tech industry are known for their confidence that they can solve any problem--even, as it turns out, the one that's defeated every other attempt so far. That's why the most far-out strategies to cheat death are being tested in America's playground for the young, deep-pocketed and brilliant: Silicon Valley.

Larry Ellison, the co-founder of Oracle, has given more than $330 million to research about aging and age-related diseases. Alphabet CEO and co-founder Larry Page launched Calico, a research company that targets ways to improve the human lifespan. Peter Thiel, co-founder of PayPal , has also invested millions in the cause, including over $7 million to the Methuselah Foundation, a nonprofit focused on life-extension therapies.

Rather than wait years for treatments to be approved by federal officials, many of them are testing ways to modify human biology that fall somewhere on the spectrum between science and entrepreneurialism. It's called biohacking, and it's one of the biggest things happening in the Bay Area.

"My goal is to live beyond 180 years," says Dave Asprey, CEO of the supplement company Bulletproof, most famous for its popularization of coffee with organic butter mixed in. "I am doing every single thing I can to make it happen for myself."

For some, that means daily pill regimens and fasting once a week. For others, it means having the blood of a young person pumped into their veins. "I see biohacking as a populist movement within health care," says Geoffrey Woo, the CEO of a company called Nootrobox that sells supplements that promise to enhance brain function.

Many scientists are skeptical. Here's what's known--and what isn't--about the latest front of humanity's fight against the inevitable.

THE HACK: It may sound vampiresque, but 50 people in the U.S. have paid $8,000 for a transfusion of plasma from someone between the ages of 16 to 25. The study is run by Ambrosia, a company based in Monterey, Calif.

THE HYPE: The transfusions are based on the idea that two-liter injections of blood from the young may confer longevity benefits. Now, in the first known human clinical trial of its kind, Ambrosia is enlisting people willing to pay the hefty price to give it a shot.

Ambrosia's founder, Jesse Karmazin, who has a medical degree but is not a licensed physician, says that after the transfusions, his team looks for changes in the recipient's blood, including markers of inflammation, cholesterol and neuron growth. "When we are young, we produce a lot of factors that are important for cellular health," he says. "As we get older, we don't produce enough of these factors. Young blood gives your body a break to repair and regenerate itself."

THE DEBATE: Scientists are roundly critical of this study, in large part because of the way it has been designed: there's no control group, it's costly to participate in, and the people enrolled don't share key characteristics that make them appropriate candidates to be looked at side by side.

"What Ambrosia is doing is not useful and could be harmful," says Irina Conboy, an associate professor of bioengineering at the University of California, Berkeley, who is also studying blood as a potential target for aging.

The concept stems from mouse research by Conboy and others. In 2005, she and her research partner and husband Michael Conboy showed that when older mice were surgically sutured to younger mice, their tissues got healthier. The takeaway was not that young blood is a cure-all, but some entrepreneurs ran with the idea. "The story has switched into a highly exaggerated search of young blood as a silver bullet to combat aging," Irina says.

In a recent follow-up study, the Conboys developed a way to exchange the blood of young and old mice without surgically joining them. They found that old mice had some improvements but that young mice experienced rapid declines.

"The big result is that a single exchange hurts the young partner more than it helps the old partner," says Michael. Ambrosia says plasma transfusions are safe and, if proven effective, should be made available.

THE BOTTOM LINE: Blood-based therapies for longevity could still be in our future, but the science isn't there yet. "Donor blood can save lives, but using it to rejuvenate oneself is counterproductive," says Irina.

THE HACK: If you could learn your risks for the most-feared diseases years before you'd actually get sick, would you? For the curious (and the brave), there's Health Nucleus, an eight-hour, $25,000 head-to-toe, inside-and-out physical exam that includes whole-genome sequencing, high-tech scanning and early diagnostics. The goal is to paint a granular picture of an individual's health and disease risk, which could then inform lifestyle and medical choices that keep you healthier, longer.

THE HYPE: Health Nucleus bills the elite program as "a genomic-powered clinical research project that has the potential to transform health care." It was founded in 2015 by J. Craig Venter, the scientist widely credited with being one of the first to sequence the human genome, and it doesn't come cheap. The Health Nucleus price tag is for a single session, during which patients get a sequencing of their genome and microbiome, a full-body MRI and an array of blood tests. When the results come in, doctors translate the findings into measurements that patients can understand--and advice they can act upon.

The Health Nucleus team believes this deluge of information can help doctors flag problems that could lead to premature death for their patients down the line. "Right now medicine is a reactionary system where if you get pain or other symptoms, then you go see your doctor and they see if they can fix it," says Venter. "It's totally different from trying to predict your risk or identifying problems early, before they cause fatal disease. If you have the right knowledge, you can save your life."

THE DEBATE: Genome sequencing can indeed pinpoint genetic risk for some cancers and other diseases. And microbiome profiles--which look at the makeup of bacteria in the gut--can provide clues about the presence of some chronic diseases. Changes in cholesterol and blood sugar can also signal illness, though that kind of blood work is routinely tested by primary-care physicians.

About 400 people ages 30 to 95 have had the physical so far, and the test has identified significant medical problems in 40% of them, according to Venter, who says they've found cancer, aneurysms and heart disease in several people without symptoms.

Still, it raises questions among its skeptics about whether or not patients can actually use most (or any) of the data they receive. It also highlights some doctors' concerns about the negative consequences of overscreening, where there is always a risk for false positive results. "When healthy people undergo scanning, it can backfire," says Dr. Eric Topol, director of the Scripps Translational Science Institute, who has studied data-driven medicine. "It can find abnormalities and lead to more tests and procedures, many of them unnecessary. It can cause harm, not to mention anxiety and expense."

This isn't news to Venter. "The criticism people throw out is 'How dare you screen healthy people?'" he says. "My response is, 'How do you know they're healthy?' We are finding pretty good evidence that many are not."

Topol says a rigorous study of the program by independent researchers could help settle the score. "If validated for benefit in this way," Topol says, "my outlook would be more positive."

THE BOTTOM LINE: Venter acknowledges that while costs may come down, the battery of tests is so far too expensive to be realistic for most. Whether it adds years to a person's life is also an open question. For now, looking into the crystal ball requires a whole lot of money--and a comfort with uncertainty.

THE HACK: Biohackers in Silicon Valley and beyond have long experimented with the idea that a fistful of supplements, taken in just the right combination, may be the antidote to aging. Now, scientists and businesspeople are experimenting with the idea that just one or two pills, taken daily, may also get the job done.

THE HYPE: Many companies sell supplements with suspected longevity benefits, but one of the more talked-about new businesses is Elysium Health, co-founded by entrepreneurs and an MIT antiaging researcher named Leonard Guarente. Elysium has created a daily supplement, called Basis, that is "designed to support long-term well-being at the cellular level." The pill isn't marketed as a cure for aging, but Elysium Health cites evidence that the ingredients in the pill increase a compound called NAD+ that the company says is "essential to hundreds of biological processes that sustain human life." Basis costs $50 for a monthly supply, and the company, which doesn't release official sales numbers, says it has tens of thousands of customers so far.

THE DEBATE: Basis contains two main ingredients: nicotinamide riboside (NR) and pterostilbene, both of which have been shown in animal studies to fight aging at the cellular level. NR creates NAD+, which is believed to spur cell rejuvenation but which declines naturally in animals as they age. In a trial of 120 healthy people from ages 60 to 80, Guarente found that people taking Basis increased their NAD+ levels by 40%. "We are trying to be rigorously based on science," he says.

Studies have shown that supplementing with the compound extends life in mice, but whether it increases human longevity is unknown. To find out if it does--and to request FDA approval for the pill's clearance as a drug--long, rigorous clinical trials would need to be done. Instead, Elysium Health has released Basis as a supplement. That prevents the company from making specific medical claims about the pills--something that's prohibited by law in the marketing of supplements.

"I think the pathway Guarente is targeting is interesting"--meaning the idea that increasing NAD+ may also slow aging--"but clinical evidence is crucial," says Dr. Nir Barzilai, a researcher at Albert Einstein College of Medicine, who also studies drugs for aging.

Other scientists question the supplement approach altogether. "There is no evidence whatsoever that [Basis] produces health benefits in humans," says Dr. Jeffrey Flier, former dean of Harvard Medical School. "Many molecules that have some apparent benefits in mice or other organisms have no benefit when studied in humans."

The company has seven Nobel Prize--winning scientists on its advisory board, a fact that has also raised some eyebrows. Flier cautions that the company's association with lauded researchers cannot replace the science required to prove that the supplements combat aging and are safe to use.

THE BOTTOM LINE: It's too early to tell whether supplements can have any life-extending effects in humans.

THE HACK: These supplements, called nootropics or sometimes "smart drugs," promise to sharpen your thinking and enhance mental abilities. Many common nootropic ingredients--including the sleep-enhancing hormone melatonin, energy-boosting B vitamins as well as caffeine--are already present in the foods and pills that people consume on a daily basis.

THE HYPE: Nootrobox, one company that makes nootropics, combines ingredients like B vitamins and caffeine with a bouquet of other ingredients to create capsules with different purposes. "Rise" pills claim to enhance memory and stamina, "Sprint" pills promise an immediate boost of clarity and energy, "Kado-3" pills offer "daily protection of brain and body," and "Yawn" pills offer what you'd expect. A combo pack of 190 capsules retails for about $135.

Nootrobox is one of the more popular nootropic startups, with more than $2 million in funding from private investors like Yahoo CEO Marissa Mayer and the venture-capital firm Andreessen Horowitz. "I think nootropics will become things we consume on a daily basis," says the company's CEO, Geoffrey Woo.

THE DEBATE: The ingredients in nootropic supplements have a "generally recognized as safe," or GRAS, designation from the FDA, and some of them have been studied for their cognitive-enhancing effects. But the unique combinations in the pills themselves haven't been proven to heighten people's mental capacity. Nootrobox says it is currently conducting clinical trials of its products.

The FDA is notoriously hands-off when it comes to the regulation of dietary supplements. In the U.S., vitamins are not required to undergo rigorous testing for effectiveness or safety before they're sold.

Many doctors are also skeptical that they make a difference in mental performance. "There's probably a lot of placebo effect," says Kimberly Urban, a postdoctoral research fellow at the Children's Hospital of Philadelphia who has studied the effects of nootropics on the brain. "I think people should use some caution, especially young people." She adds that while these supplements may in fact be safe, there's no scientific research to prove it.

THE BOTTOM LINE: Many nootropics on the market are probably less sugary and lower in caffeine than most energy drinks, which often contain similar ingredients to those in the pills. Still, the notion that they make people sharper is largely unproven. So until independent clinical trials prove otherwise, it's buyer beware.

THE HACK: Calorie restriction--the practice of consuming nothing but water for a day at a time or drastically slashing calories a few days per week--has been popular for decades among eternal-youth seekers and health nuts alike. Now some companies are taking the guesswork out of it with fasting-diet meal-delivery kits.

THE HYPE: Not eating on a regular basis certainly sounds unpleasant, but proponents say that doing so comes with the benefits of better health, a stronger immune system and possibly even a longer life.

To help people get closer to this goal, L-Nutra, a Los Angeles--based company, offers a five-day, ultra-low-calorie meal kit called ProLon, which is designed to mimic fasting and promote health and longevity.

The meal kit includes energy bars, plant-based snacks, vegetable soups and algal-oil supplements that add up to a total of 770 to 1,100 calories a day. A five-day kit that must be ordered by a doctor costs $299.

THE DEBATE: Studies do show that calorie-restricted diets are linked to longer life expectancy. It's not clear why, exactly, but some scientists suspect that stressing the body kicks it into a temporary mode that leads to the creation of healthy new cells. Other research suggests that a very-low-calorie diet may make the body more responsive to cancer treatment and can slow the progression of multiple sclerosis.

A recent two-year study found that people who cut their calorie intake by 25% lost an average of 10% of their body weight, slept better and were even cheerier compared with those who didn't diet.

"Doctors can offer patients this as an alternative to drugs," says Valter Longo, director of the University of Southern California Longevity Institute and founder of L-Nutra. (Longo says he doesn't receive a salary from his work with L-Nutra.)

Still, not everyone agrees that the evidence is strong enough to support the price tag--or the effort required. "I certainly wouldn't do it," says Rozalyn Anderson, a researcher at the University of Wisconsin--Madison, who studies calorie restriction in monkeys. "Life is too short, even if calorie restriction extends it."

The real promise of this kind of research is identifying cell pathways that are involved in aging and activated during fasting, she says. Ultimately this could lead to the development of a drug that could trigger those same pathways without requiring people to eat less.

THE BOTTOM LINE: Occasional calorie restriction does appear to have health benefits, but how much comes from weight loss and how much comes from healthy cell changes needs to be further explored. Widely agreed upon is that any version of a fasting diet should be done under a physician's supervision.

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Telomeres nature’s anti-ageing scheme – Varsity Online

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Zi Ran looks into the exciting biology surrounding telomeres and their potential impact

The thread of never-ending life has always been a part of the canvas of myths and religion subsequently morphed seamlessly into everyday culture. Every religion and culture has their own telling of the tale. The Abrahamic religions have heaven, the Norse gods ate Iunns apples, the Greek gods ate ambrosia and drank nectar, the Taoists sought the elixir of life, and the medieval alchemists sought the philosophers stone. Though these ancient symbols may have been metaphoric, with current technology eternal youth feels to be almost within our grasp. With organisations like Google Calico, A4M (American Academy of Anti-Aging Medicine), Human Longevity Inc and sponsors like Peter Thiel and Mark Zuckerberg, it seems as though humanity may finally taste that fountain of life.

To find immortality, one must understand mortality. Cells seemingly repair and divide without end, but they exhibit signs of ageing as well. The crux of the issue lies in the inherent structure of our genetic material, DNA. Human DNA is linear, so there must be two ends to the double helix. Every time DNA is replicated, information on the ends of the strands are lost. With increasing divisions, more and more information is lost to the point where the cell is no longer able to function cells senescence. Cells with this kind of DNA structure must have an extra layer of molecular protection which ensure many healthy divisions before their eventual death. These protective elements are called telomeres. Telomere research has been a hot topic within the anti-ageing community, as its length is directly correlated to longevity. These DNA aglets are extra pieces of DNA which cap on to the ends of the double helix strand and tightly wraps itself together to protect the genetic material both from chemical and mechanical damage. However, this method is not fool-proof. Telomeres also run out, and with time all cells eventually die.

The miracle of the fountain of life, if it exists at all, can only be found in the moment of conception. In embryos, the DNA is refreshed, and old used telomeres are extended. Embryonic cells are a rare type of cells which express telomerase, the only protein capable of extending the length of telomeres. These little molecular machines use RNA as a template to extend the depleted telomeres, elongating the lifespan of the cell. Telomerases are also expressed in some stem cells, which supply the body with red blood cells and repair large damages. As attractive as telomerases sound as a solution to age, their over-expression can also become a problem. Many tumours and cancer types use telomerase as a tool to extend their lifespan indefinitely, outliving their healthy counterparts and taking over the body. To fine-tune the activity of this protein such that humans achieve eternal life while escaping the potential over-proliferation of cells is something that has yet to be achieved.

The most important breakthrough of 2016?

Telomeres, all in all, may only be one piece of the longevity biochemical puzzle. Many other biological processes are affected by age, although the precise mechanisms remain shrouded in mystery. Mitochondria become less efficient, transport to and from the nucleus becomes much less regulated, proteins are misshapen more often, and the DNA racks up too many mutations to efficiently repair them. It looks as though humanity still has so much to learn in terms of mortality that the seemingly tiny gap to eternal life may actually be a journey of a thousand miles.

Once we understand the essentials of life, will eternity still be attractive? The underlying basis of all living things is maintenance of a dynamic equilibrium, meaning that balance is maintained through constant life and death. The confusion of age for life has been recorded since the time of the ancient Greeks. When Eos mistakenly asked on Tithonus behalf for immortality and not eternal youth, what she really obtained from Zeus was eternal torture. The ancient Homeric hymns only remember Tithonus as a withered old man with no strength to even sit up, certainly an anecdote to keep us grounded in our search

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Too Much Vitamin B3 (Niacin) Might Cause Eczema – American Council on Science and Health

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For the average person, dietary supplements are a waste of time and money. Assuming a person makes an effort toward maintaining a somewhat balanced diet, nutrients are provided in sufficient quantities from everyday food. Only people who havea metabolic deficiency or areat risk of developing a specificdisease should supplement their diets with particular minerals or vitamins.

Still, many people take multivitamins "just to be safe." That may not be a good idea, as some research has suggested that taking supplements unnecessarily may lead to adverse health outcomes. Now, a new paper suggests that people who consume too much vitamin B3 (niacin) might be at higher risk of developing eczema.

Becausea previous study showed that niacin supplements reduced water loss through the skin, the authors hypothesized that niacin may help prevent eczema, which manifests as dry, itchy skin. To their surprise, they found that niacin supplements appeared to promote the development of eczema.

The team collected data from the Nurse's Health Study 2 (NHS2), a cohort analysis based upon surveys filled out by a large group of nurses every other year. The researchers first categorized the participants by dietary niacin intake. No matter how much niacin was consumed in the diet, there was no link to the development of eczema.

However, the authors found that participants who supplemented their diets with niacin (specifically, more than 18 mg per day) increased their risk of eczema by about 16%.

This is hardly slam-dunk evidence. The NHS2 study includes mostly white women, so the results may not apply to other groups of people. Also, it is possible that some other component in the supplement, not niacin itself, is causing the increase in eczema.

Still, this paper serves as yet more evidence that, for the average person,vitamins aren't just useless but perhaps mildly detrimental. When an adverse effect like eczema is linked to consuming 18+ mg of supplemental niacin per day, it makes 500 mg tablets (see upper left image) seem like an obscenely high dose.

*Fun fact: Hamsters that do not consume enough niacin will eat their siblings or offspring.

Source:Aaron M. Drucker, Wen-Qing Li, Min Kyung Park,Tricia Li, Abrar A. Qureshi, Eunyoung Cho. "Niacin intake and incident adult-onset atopic dermatitis in women."J Allergy Clin Immunol. Article in press. Published online: 2017. DOI:10.1016/j.jaci.2016.12.956

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FDA OKs Injectable Psoriasis Drug for Tough Cases – WebMD

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By Robert Preidt

HealthDay Reporter

THURSDAY, Feb. 16, 2017 (HealthDay News) -- A new drug to treat tough cases of the skin condition psoriasis has won approval from the U.S. Food and Drug Administration.

Valeant Pharmaceuticals' injectable drug Siliq (brodalumab) was approved for adults with moderate-to-severe psoriasis that isn't responding to other recommended treatments. However, the drug carries a warning about increased risk for suicidal behavior.

Psoriasis is characterized by raised patches of red skin and flaking. The condition usually begins between ages 15 and 35 and is thought to be an autoimmune disorder, meaning the body mistakenly attacks healthy cells.

"Moderate-to-severe plaque psoriasis can cause significant skin irritation and discomfort for patients, and today's approval provides patients with another treatment option for their psoriasis," said the FDA's Dr. Julie Beitz.

Beitz is director of the Office of Drug Evaluation III in the FDA's Center for Drug Evaluation and Research.

The drug is intended for patients who are candidates for systemic therapy -- treatment with pills or injectable drugs that travel through the bloodstream -- or phototherapy (ultraviolet light treatment), and have failed to respond or stopped responding to past therapies, the FDA said.

The drug works by inhibiting the inflammatory response that contributes to development of plaque psoriasis, the most common form of the skin disease, the FDA said.

Siliq's approval was based on three clinical trials that included more than 4,300 patients. Compared to those who took a placebo, more of those participants who took the drug had skin that was clear or almost clear, the agency said.

However, the drug carries a "boxed warning" about the risk of suicidal thoughts and attempts and it's only available through a suicide risk evaluation program, the FDA said.

Among patients who took Siliq, those with a history of suicide attempts or depression had greater risk of suicidal thoughts and attempts compared to others, according to trial results. However, a direct cause-and-effect relationship wasn't established.

"Patients and their health care providers should discuss the benefits and risks of Siliq before considering treatment," Beitz said in an agency news release.

Because Siliq affects the immune system, patients also may have a greater risk of getting an infection, or an allergic or autoimmune condition, the FDA said.

The most common side effects reported in the trials included joint and muscle pain, headache, fatigue, nausea or diarrhea, low white blood cell count and fungal infections.

WebMD News from HealthDay

SOURCE: U.S. Food and Drug Administration, news release, Feb. 15, 2017

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Stepping up the hunt for genetic diseases – Medical Xpress

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February 16, 2017 Credit: UNIGE

When a child is conceived, he or she receives DNA from both parents. The child's own genome thus consists of a maternal and a paternal genome. However, some genesabout 100 out of the 20,000 encoded genes are exclusively expressed either from the maternal or from the paternal genome, with the other copy of the gene remaining silent. We know that these imprinted genes are more likely to lead to serious genetic diseases, such as PraderWilli or Angelman syndrome. Researchers at the University of Geneva (UNIGE), Switzerland, have devised a new technique, based on a combination of biology and bioinformatics, to quickly and accurately detect the imprinted genes expressed in each of the cell types that constitute the human organs. This major breakthrough will improve our understanding and diagnosis of genetic diseases. The study can be read in full in the American Journal of Human Genetics.

The research team, led by Professor Stylianos Antonarakis from the Department of Genetic Medicine and Development in the Faculty of Medicine at UNIGE, focused on genomic imprinting. This is a set of genes exclusively expressed from the genetic code inherited either from the father (the paternal allele) or from the mother (maternal allele). Why is there so much interest in the identification of the imprinted genes? Because if a deleterious mutation affects the functional allele, it cannot be compensated by the expression of the second silent allele, likely causing a serious genetic disease. The goal, therefore, is to determine the imprinted genes in all cell types of human body tissues that are liable to cause these kind of diseases.

Until recently, millions of cells were analysed together without distinction. "We have now developed a new technique with a better resolution, known as Human Single-Cell Allele-Specific Gene Expression," explains Christelle Borel, UNIGE researcher. "The process can be used to simultaneously examine the expression of the two alleles, paternal and maternal, of all known genes in each individual cell. The method is fast and can be carried out on thousands of single cells with the utmost precision using next-generation sequencing technology." The heterogeneity of each tissue of the body is thus analysed in detail while searching for imprinted genes in disease-relevant tissue. The individual's genome is sequenced, as is the genome of both parents, in order to identify the parental origin of the alleles transcribed in the person's single cell.

Each cell is unique

Federico Santoni, first author of the study and researcher at UNIGE and HUG (Geneva University Hospitals) further explains, "We establish the profile of the allelic expression for thousands of genes in each single cell. We then process this data with a novel computational and statistical framework to identify the specific signature of each imprinted gene, enabling us to accurately record them." This new technique redefines the landscape of imprinted genes by examining all cell types, and can be applied to all tissues affected by diseases, such as cardiac and brain tissue. Moreover, the scientists have discovered novel imprinted genes and demonstrated that some were restricted to certain tissues or cell types.

This technique focuses on the specific characteristics of each individual by treating each cell as a single entity. This concept, called Single-cell Genomics, is part of an emerging field that is assuming an all-important role at UNIGE, which sees it as the future of medicine that will be personalised rather than generalised. Thanks to the technique pioneered by UNIGE researchers, it will be possible to identify new disease causing genes and to adapt a specific and targeted treatment for individual patients.

Explore further: Expanding the brain: Research identifies more than 40 new imprinted genes

More information: Federico A. Santoni et al. Detection of Imprinted Genes by Single-Cell Allele-Specific Gene Expression, The American Journal of Human Genetics (2017). DOI: 10.1016/j.ajhg.2017.01.028

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Rare Muscle Disease Treated Successfully with Gene Therapy – Genetic Engineering & Biotechnology News

Posted: at 12:48 am

Work on gene therapy is showing significant progress for restoring muscle strength and prolonging lives in dogs with a previously incurable, inherited neuromuscular disease, according to scientists at the University of Washington (UW) Medicine Institute for Stem Cell and Regenerative Medicine.

The disease arises from a mutation in genes that normally make myotubularin, a protein essential for proper muscle function. Puppies with this naturally occurring mutation exhibit several features of babies with the same defective gene. The rare disorder, called X-linked myotubular myopathy, or XLMTM, affects only males. It causes fatal muscle wasting. Both dogs and boys with the disease typically succumb in early life due to breathing difficulties.

For decades, researchers have struggled to find suitable treatments for genetic muscle diseases like this one. Collaborating research groups in the United States and France found a way to safely replace the disease-causing MTM gene with a healthy gene throughout the entire musculature of affected dogs.

Their most recent findings ("Systemic AAV8-Mediated Gene Therapy Drives Whole-Body Correction of Myotubular Myopathy in Dogs") werepublished online inMolecular Therapy.The paper reports that diseased dogs treated with a single infusion of the corrective therapy were indistinguishable from normal animals 1 year later.

"This regenerative technology allowed dogs that otherwise would have perished to complete restoration of normal health," said Martin K. "Casey" Childers, Ph.D., UW medicine researcher and physician. Dr. Childers is a professor of rehabilitation medicine at the University of Washington School of Medicine and co-director of the Institute for Stem Cell and Regenerative Medicine.

Gene therapy holds the promise to treat many inherited diseases. To date, this approach has not been widely translated into treatment of skeletal muscle disorders.

"We report here a gene therapy dose-finding study in a large animal model of a severe muscle disease where a single treatment resulted in dramatic rescue," said Dr. Childers. The findings demonstrate potential application across a wide range of diseases and broadly translate to human studies. The data supports the development of gene therapy clinical trials for myotubular myopathy, the researchers concluded.

The study was conducted in collaboration with Harvard University, Medical College of Wisconsin, Virginia Tech, INSERM, and Genethon.

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Human genome editing report strikes the right balance between risks and benefits – Medical Xpress

Posted: at 12:48 am

February 16, 2017 by Merlin Crossley, The Conversation Gene therapy is growing in its capabilities, but there should be limits to its use. Credit: Shutterstock

If you recognise the words "CRISPR-mediated gene editing", then you'll know that our ability to alter DNA has recently become much more efficient, faster and cheaper.

This has inevitably led to serious discussions about gene therapy, which is the direct modification of someone's DNA to rectify a genetic disorder, such as sickle cell anaemia or haemophilia. And you may also have heard of deliberate genetic enhancement, to realise a healthy person's dreams of improving their genome.

Both of these issues have now been tackled in a comprehensive report on gene editing released today by the US National Academy of Science and National Academy of Medicine.

The message is fairly simple: relax, we've seen this all before, little if any harm has eventuated, and society is well placed to move forward together on this.

A definite maybe

Of all human technologies, recombinant DNA has arguably been one of the safest. There have been multiple benefits in both medicine and agriculture. And the legitimate concerns that arose when viruses were first mixed with bacterial genes, when cloning was first introduced, and when stem cells were developed, have not come to pass.

I cannot list all the benefits here, but if you have received the Hepatitis B vaccine or Australian Ian Fraser's Gardasil vaccine, which protects against cervical cancer viruses, you have been protected from disease thanks to recombinant DNA technology.

However, you probably haven't received somatic gene therapy, which is gene alteration directed at fixing one cell type, such as defective blood or liver cells. This is because this therapy only touches a tiny number of people, probably fewer than 1,000 worldwide, and again the benefits have outweighed the risks.

But there is one new message in the report that will grab the headlines.

That is the view on human germline gene therapy, which entails modifications that would be passed on to children and then to their children. This kind of gene therapy has been considered highly controversial. But this time, instead of a simple no thanks there's a definite maybe, provided the therapy is targeted at a severe disease as a last resort.

There will be alarm in some circles at the very mention of germline gene therapy, although perhaps not from the very few people who might be contemplating such treatment for the sake of their future children.

The authors of the report, who are among the mostly highly respected experts in the world, are well aware that many people will not be comfortable with the thought of germline gene therapy. They stress the need for extensive consultation, the meeting of strict criteria, and close regulation.

But in weighing up safety and efficacy, social and individual benefit, they clearly don't want to see a reflex ban put in place that may limit options if this technology can be used to make the life of some individuals better.

On one hand, they are right. This technology is not a threat to the fabric of society. Nor, I'd say, is this a genie that could not be put back in the bottle; gene editing could be reversed.

Nor, like the Sorcerer's Apprentice's broomsticks, will it multiply and spread when we try to restrain it. This is not like letting slip a virus, cane toads, oozing radioactive waste or carbon emissions into the atmosphere.

Seeking germline gene therapy in order to have a disease-free child would be a choice made at a personal level and those not wishing to participate should never feel compelled to do so.

Except, of course, the children who would not have a say in it. But also for them the risks might well outweigh the benefits. And, one way or another, parents already make life-determining choices for their children and sometimes for their children's children.

Even those seeking germline therapy for the sake of their children would mostly have alternatives, such as preimplantation diagnosis, which itself also has ethical considerations. There are no easy answers here.

So I can understand the report's conclusion, although I also believe there are risks, which I'll mention below.

Hard to abuse

There are other aspects of the report worth mentioning. It confirms that we already do properly regulate laboratory-based gene modifications, and we have learned so much from previous somatic gene therapy efforts that we are well placed to push on safely with both research and somatic treatments. I agree with this.

It also says that actual genetic enhancements should be avoided. There is evidence that society is uncomfortable with the idea of individuals, who are not suffering from disease, improving either themselves through somatic therapy or their bloodlines through germline genetic enhancement.

Some people might want more copies of the p53 tumour suppressing gene or to lose their CCR5 gene, which helps HIV invade cells, in order to give their children possible protection from cancer or HIV respectively, but I'd have to say it isn't worth the risk.

I would add that, ethical reservations aside, the sheer complexity of our genomes, and the rather involved and lengthy process of human reproduction, means that I have no concerns that even the craziest world leader could ever generate an army of super-mutants. Such an ambition would be defeated by not knowing which genes to alter, not to mention the requirement to assemble tens of thousands of surrogate mothers, then wait 20 years for the army to mature.

Yes, it is possible that someone somewhere will attempt germline gene enhancement as a stunt. That would be wrong and dangerous, and a risk for the child. But it would not threaten society any more deeply than many other obscene and regrettable individual crimes that sadly occur every day.

Germline gene therapy is illegal in many countries, and although there is a risk that unfortunate "medical tourism" may occur at some stage, I don't expect this to be a greater problem than the already widespread snake-oil selling that is a feature of many economies.

No emergency

So am I comfortable with this report and confident that it covers the ethical issues? I think it is superbly written. It is accurate, up to date, balanced, thoughtful, and covers experiments, somatic therapy, germline therapy, genetic enhancement, societal responses, and the need for public consultation and careful regulation. There is no emergency here.

My main concern is that raising the prospect of germline gene therapy will trigger discussions that will divert us from more pressing issues.

I do worry that introducing this apex concept as a possibility may increase the number of people who fixate on what gene therapy could deliver and thus may be lured into medical tourism, both desperate patients and also foolish investors, and all the while charlatans will profit from peddling promise.

I worry that raising hopes too high too quickly will ultimately cause a backlash against more moderate science.

I also worry that even conventional funding bodies will succumb to understandable pressures to fund translational research prematurely and this will actually waste large amounts of valuable public money.

And I worry about a hysterical reaction that could divide society along political lines with people lining up for or against germline gene therapy based on their political positions or personal beliefs rather than a sober examination of the facts, risks and contexts.

Finally, I worry that the focus on human modification will distract us from other issues, such as the use of CRISPR-mediated gene drives that could be used to eradicate rapidly reproducing organisms such as mosquitoes, and could thus be used for both great good or great harm.

But I don't feel the burden of worry too much because I know that, as a scientist, I can and should share the weight of my concerns with society.

Explore further: With stringent oversight, heritable human genome editing could be allowed: report

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

Clinical trials for genome editing of the human germline - adding, removing, or replacing DNA base pairs in gametes or early embryos - could be permitted in the future, but only for serious conditions under stringent oversight, ...

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The National Academy of Sciences and National Academy of Medicine issued a 258-page report Tuesday (Feb. 14) focused on human genome editing. It lays out principles and recommendations for the U.S. government and governments ...

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Don't expect designer babies any time soonbut a major new ethics report leaves open the possibility of one day altering human heredity to fight genetic diseases, with stringent oversight, using new tools that precisely ...

Personalized medicine, which involves tailoring health care to each person's unique genetic makeup, has the potential to transform how we diagnose, prevent and treat disease. After all, no two people are alike. Mapping a ...

Work on gene therapy is showing significant progress for restoring muscle strength and prolonging lives in dogs with a previously incurable, inherited neuromuscular disease. UW Medicine Institute for Stem Cell and Regenerative ...

A genomic study of baldness identified more than 200 genetic regions involved in this common but potentially embarrassing condition. These genetic variants could be used to predict a man's chance of severe hair loss. The ...

Purdue University and Indiana University School of Medicine scientists were able to force an epigenetic reaction that turns on and off a gene known to determine the fate of the neural stem cells, a finding that could lead ...

Just before Rare Disease Day 2017, a study from the Monell Center and collaborating institutions provides new insight into the causes of trimethylaminura (TMAU), a genetically-transmitted metabolic disorder that leads to ...

Monash University and Danish researchers have discovered a gene in worms that could help break the cycle of overeating and under-exercising that can lead to obesity.

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