Roomy cages built from DNA could one day deliver drugs, devices

Move over, nanotechnologists, and make room for the biggest of the small. Scientists at the Harvard’s Wyss Institute have built a set of self-assembling DNA cages one-tenth as wide as a bacterium. The structures are some of the largest and most complex structures ever constructed solely from DNA, they report today’s online edition of Science.Moreover, the scientists visualized them using a DNA-based super-resolution microscopy method — and obtained the first sharp 3D optical images of intact synthetic DNA nanostructures in solution.In the future, scientists could potentially coat the DNA cages to enclose their contents, packaging drugs for delivery to tissues. And, like a roomy closet, the cage could be modified with chemical hooks that could be used to hang other components such as proteins or gold nanoparticles. This could help scientists build a variety of technologies, including tiny power plants, miniscule factories that produce specialty chemicals, or high-sensitivity photonic sensors that diagnose disease by detecting molecules produced by abnormal tissue.”I see exciting possibilities for this technology,” said Peng Yin, Ph.D., a Core Faculty member at the Wyss Institute and Assistant Professor of Systems Biology at Harvard Medical School, and senior author of the paper.Building with DNADNA is best known as a keeper of genetic information. But scientists in the emerging field of DNA nanotechnology are exploring ways to use it to build tiny structures for a variety of applications. These structures are programmable, in that scientists can specify the sequence of letters, or bases, in the DNA, and those sequences then determine the structure it creates.So far most researchers in the field have used a method called DNA origami, in which short strands of DNA staple two or three separate segments of a much longer strand together, causing that strand to fold into a precise shape. DNA origami was pioneered in part by Wyss Institute Core Faculty member William Shih, Ph.D., who is also an Associate Professor in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and the Department of Cancer Biology at the Dana-Farber Cancer Institute.Yin’s team has built different types of DNA structures, including a modular set of parts called single-stranded DNA tiles or DNA bricks. Like LEGO bricks, these parts can be added or removed independently. Unlike LEGO bricks, they spontaneously self-assemble.But for some applications, scientists might need to build much larger DNA structures than anyone has built so far. …

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Meet your match: Using algorithms to spark collaboration between scientists

Speed dating, in which potential lovers size each other up in brief 10 minute encounters before moving on to the next person, can be an awkward and time-wasting affair. Finding the perfect research partnership is often just as tough. Speed dating-style techniques are increasingly used at academics conferences, but can be equally frustrating — with busy academics being pushed into too many pointless encounters.But now a group of scientists led by geneticist Rafael Carazo Salas have constructed a system that could revolutionise conference speed dating — by treating scientists like genes.Using mathematical algorithms, the team created a method of matching conference-goers according to pre-set criteria, bringing about unforeseen collaboration opportunities while also enabling “would-like-to-meet” match-ups across disciplines and knowledge areas. The results have been recently published in the open-access journal eLife.Funded by the Royal Society to run a small-scale satellite conference on cell polarity, the researchers wanted to find a way to not only break the ice between scientists who did not know each other, but also to “break the heat” — to encourage big name scientists to step outside of their usual small circle, and mix with up-and-coming scientists.”We wanted to avoid the usual pattern that happens at conferences, especially at interdisciplinary meetings, of like sticking with like. Then we came up with an idea — what if we treated the delegates like we treat genes, and used mathematical algorithms to build a connectivity picture that could enable new links to be made?” said Carazo Salas, from the Gurdon Institute and Genetics Department of Cambridge University, who co-developed the technique with colleagues Federico Vaggi and Attila Csikasz-Nagy from Fondazione Edmund Mach, Italy.In the lead-up to the conference, delegates were asked to submit information about their research areas and disciplines and also to come up with a ‘wish list’ of specialist areas that they would like to know more about.”The conference started in a predictable way. After the first couple of talks, questions came entirely from people in the first few rows. We then did a brief presentation about the “speed dating” session that was about to happen. People’s eyes lit up when they got the game — the notion of being treated like genes seemed to appeal.”In the first speed-dating round, the 40 delegates were each paired up with someone who was not known to them and who had a very different knowledge base — so someone specialising in X technique might be paired with a specialist in Y. Pairs were given around 10 minutes to talk and then moved on to new pairs, so that each person met a total of four other people they knew very little about.”The atmosphere in the room after the first round of speed dating was entirely different. There was a buzz, and at the next set of talks questions came from all over the room, not just the usual couple of rows at the front.”In the second round, the pairings made use of the wish lists the delegates had created. …

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Hormone released after exercise can ‘predict’ biological age

Scientists from Aston University (UK) have discovered a potential molecular link between Irisin, a recently identified hormone released from muscle after bouts of exercise, and the aging process.Irisin, which is naturally present in humans, is capable of reprograming the body’s fat cells to burn energy instead of storing it. This increases the metabolic rate and is thought to have potential anti-obesity effects.The research team led by Dr James Brown have proven a significant link exists between Irisin levels in the blood and a biological marker of aging called telomere length. Telomeres are small regions found at the end of chromosomes that shorten as cells within the body replicate. Short telomere length has been linked to many age-related diseases including cancer, heart disease and Alzheimer’s disease.Using a population of healthy, non-obese individuals, the team has shown those individuals who had higher levels of Irisin were found to have longer telomeres. The finding provides a potential molecular link between keeping active and healthy aging with those having higher Irisin levels more ‘biological young’ than those with lower levels of the hormone.Dr James Brown from Aston’s Research Centre for Healthy Ageing, said: “Exercise is known to have wide ranging benefits, from cardiovascular protection to weight loss. Recent research has suggested that exercise can protect people from both physical and mental decline with aging. Our latest findings now provide a potential molecular link between keeping active and a healthy aging process.”Irisin itself is secreted from muscle in response to exercise and is capable of reprograming the body’s fat cells to burn energy instead of storing it. This increases the metabolic rate and is thought to have potential weight loss effects, which in turn could help with conditions such as type-2 diabetes.Story Source:The above story is based on materials provided by Aston University. Note: Materials may be edited for content and length.

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Embryology: Scientists crack open ‘black box’ of development and see a ‘rosette’

We know much about how embryos develop, but one key stage — implantation — has remained a mystery. Now, scientists from Cambridge have discovered a way to study and film this ‘black box’ of development. Their results — which will lead to the rewriting of biology text books worldwide — are published in the journal Cell.Embryo development in mammals occurs in two phases. During the first phase, pre-implantation, the embryo is a small, free-floating ball of cells called a blastocyst. In the second, post-implantation, phase the blastocyst embeds itself in the mother’s uterus.While blastocysts can be grown and studied outside the body, the same has not been true from implantation. And because embryos are so closely connected to their mothers, implantation has also been difficult to study in the womb.According to study author Professor Magdalena Zernicka-Goetz of the University of Cambridge: “We know a lot about pre-implantation, but what happens after implantation — and particularly the moment of implantation — is an enigma.”Scientists are interested in studying implantation because the embryo undergoes huge changes in such a short space of time.”During these two days, it goes from a relatively simple ball to a much larger, more complex cup-like structure, but exactly how that happens was a mystery — a black box of development. That is why we needed to develop a method that would allow us to culture and study embryos during implantation,” she explained.Working with mouse cells, Professor Zernicka-Goetz and her colleague Dr Ivan Bedzhov succeeded in creating the right conditions outside the womb to study the implantation process.To be able to support development, they created a system comprising a gel and medium that, as well as having the right chemical and biological properties, was of similar elasticity to uterine tissue. Crucially, this gel was transparent to optical light, allowing then to film the embryo during implantation.This new method revealed that on its way from ball to cup, the blastocyst becomes a ‘rosette’ of wedge-shaped cells, a structure never before seen by scientists.”It’s a beautiful structure. This rosette is what a mouse looks like on the 4th day of its life, and most likely what we look like on the 7th day of ours, and it’s fascinating how beautiful we are then, and how these small cells organise so perfectly to allow us to develop.”As well as answering a fundamental question in developmental biology, the new method will allow scientists to study embryo growth and development at implantation for the first time, which could help improve the success of IVF, and extend our knowledge of stem cells, which could advance their use in regenerative medicine.The findings also mean developmental biology text books will need rewriting. “The text books make an educated guess of what happened during this part of development, but we now know that what I learned and what I teach my students about this was totally wrong,” said Professor Zernicka-Goetz.Story Source:The above story is based on materials provided by University of Cambridge. …

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Superconductivity in orbit: Scientists find new path to loss-free electricity

Brookhaven Lab researchers captured the distribution of multiple orbital electrons to help explain the emergence of superconductivity in iron-based materials. Armed with just the right atomic arrangements, superconductors allow electricity to flow without loss and radically enhance energy generation, delivery, and storage. Scientists tweak these superconductor recipes by swapping out elements or manipulating the valence electrons in an atom’s outermost orbital shell to strike the perfect conductive balance. Most high-temperature superconductors contain atoms with only one orbital impacting performance — but what about mixing those elements with more complex configurations?Now, researchers at the U.S. Department of Energy’s Brookhaven National Laboratory have combined atoms with multiple orbitals and precisely pinned down their electron distributions. Using advanced electron diffraction techniques, the scientists discovered that orbital fluctuations in iron-based compounds induce strongly coupled polarizations that can enhance electron pairing — the essential mechanism behind superconductivity. The study, set to publish soon in the journal Physical Review Letters, provides a breakthrough method for exploring and improving superconductivity in a wide range of new materials.While the effect of doping the multi-orbital barium iron arsenic — customizing its crucial outer electron count by adding cobalt — mirrors the emergence of high-temperature superconductivity in simpler systems, the mechanism itself may be entirely different.”Now superconductor theory can incorporate proof of strong coupling between iron and arsenic in these dense electron cloud interactions,” said Brookhaven Lab physicist and study coauthor Weiguo Yin. “This unexpected discovery brings together both orbital fluctuation theory and the 50-year-old ‘excitonic’ theory for high-temperature superconductivity, opening a new frontier for condensed matter physics.”Atomic Jungle GymImagine a child playing inside a jungle gym, weaving through holes in the multicolored metal matrix in much the same way that electricity flows through materials. This particular kid happens to be wearing a powerful magnetic belt that repels the metal bars as she climbs. This causes the jungle gym’s grid-like structure to transform into an open tunnel, allowing the child to slide along effortlessly. …

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Cat parasite found in western Arctic Beluga deemed infectious

University of British Columbia scientists have found for the first time an infectious form of the cat parasite Toxoplasma gondii in western Arctic Beluga, prompting a health advisory to the Inuit people who eat whale meat.The same team also discovered a new strain of the parasite, previously sequestered in the icy north, that is responsible for killing 406 grey seals in the north Atlantic in 2012.Presenting their findings today at the 2014 Annual Meeting of the American Association for the Advancement of Science (AAAS), Michael Grigg and Stephen Raverty from UBC’s Marine Mammal Research Unit say that the “big thaw” occurring in the Arctic is allowing never-before-seen movement of pathogens between the Arctic and the lower latitudes.”Ice is a major eco-barrier for pathogens,” says Michael Grigg, a molecular parasitologist with the U.S. National Institutes of Health and an adjunct professor at UBC. “What we’re seeing with the big thaw is the liberation of pathogens gaining access to vulnerable new hosts and wreaking havoc.”Toxoplasmosis, also known as kitty litter disease, is the leading cause of infectious blindness in humans and can be fatal to fetuses and to people and animals with compromised immune systems.”Belugas are not only an integral part of Inuit culture and folklore, but also a major staple of the traditional diet. Hunters and community members are very concerned about food safety and security,” says Raverty, a veterinary pathologist with the B.C. Ministry of Agriculture and Lands’ Animal Health Centre and an adjunct professor at UBC. Raverty has led the systematic sampling and screening of hunter-harvested Beluga for 14 years.Grigg has also identified the culprit of the 2012 grey seal die-off as a new strain of Sarcocystis. While not harmful to humans, the Arctic parasite, which was named Sarcocystis pinnipedi at the AAAS meeting today, has now killed an endangered Steller sea lion, seals, Hawaiian monk seals, walruses, polar and grizzly bears in Alaska and as far south as British Columbia.Story Source:The above story is based on materials provided by University of British Columbia. Note: Materials may be edited for content and length.

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Ancient reptile birth preserved in fossil: Ichthyosaur fossil may show oldest live reptilian birth

An ichthyosaur fossil may show the earliest live birth from an ancient Mesozoic marine reptile, according to a study published February 12, 2014 in PLOS ONE by Ryosuke Motani from the University of California, Davis, and colleagues.Ichthyosaurs were giant marine reptiles that evolved from land reptiles and moved to the water. Scientists report a new fossil specimen that belongs to Chaohusaurus (Reptilia, Ichthyopterygia), the oldest of Mesozoic marine reptiles that lived approximately 248 million years ago. The partial skeleton was recovered in China and may show a live birth. The maternal skeleton was associated with three embryos and neonates: one inside the mother, another exiting the pelvis-with half the body still inside the mother-and the third outside of the mother. The headfirst birth posture of the second embryo indicates that live births in ichthyosaurs may have taken place on land, instead of in the water, as some studies have previously suggested.The new specimen may contain the oldest fossil embryos of Mesozoic marine reptile, about 10 million years older than those indicated on previous records. The authors also suggest that live births in land reptiles may have appeared much earlier than previously thought.Dr. Motani added, “The study reports the oldest vertebrate fossil to capture the ‘moment’ of live-birth, with a baby emerging from the pelvis of its mother. The 248-million-year old fossil of an ichthyosaur suggests that live-bearing evolved on land and not in the sea.”Story Source:The above story is based on materials provided by PLOS. Note: Materials may be edited for content and length.

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First global geologic map of Jupiter’s largest moon Ganymede details an icy world

More than 400 years after its discovery by Galileo, the largest moon in the solar system has finally claimed a spot on the map.A team of scientists led by Wes Patterson of the Johns Hopkins Applied Physics Laboratory (APL), Laurel, Md., and Geoffrey Collins of Wheaton College, Norton, Mass., has produced the first global geologic map of Ganymede, a Galilean moon of Jupiter. Published by the U.S. Geological Survey, the map technically illustrates the varied geologic character of Ganymede’s surface, and is the first complete global geologic map of an icy, outer-planet moon.Patterson, Collins and colleagues used images from NASA’s Voyager and Galileo missions to create the map. It’s only the fourth of its kind covering a planetary satellite; similar maps exist for Earth’s moon as well as Jupiter’s moons Io and Callisto.”By mapping all of Ganymede’s surface, we can more accurately address scientific questions regarding the formation and evolution of this truly unique moon,” says Patterson, a planetary scientist.Since its discovery in January 1610, Ganymede has been the focus of repeated observation, first by Earth-based telescopes, and later by flyby missions and spacecraft orbiting Jupiter. These studies depict a complex icy world whose surface is characterized by the striking contrast between its two major terrain types: the dark, very old, highly cratered regions; and the lighter, somewhat younger (but still ancient) regions marked with an extensive array of grooves and ridges.  With a diameter of 3,280 miles (5,262 kilometers), Ganymede is larger than both planet Mercury and dwarf planet Pluto. It’s also the only satellite in the solar system known to have its own magnetosphere. The map details geologic features of the moon that formed and evolved over much of our solar system’s history. These features record evidence of Ganymede’s internal evolution, its dynamical interactions with the other Galilean satellites, and the evolution of the small bodies that have impacted Ganymede’s surface.The new chart will be a valuable tool for researchers to compare the geologic characters of other icy moons, since almost any type of feature that is found on other icy satellites has a similar feature somewhere on Ganymede. And with a surface over half as large as all the land area on Earth, Ganymede offers a wide variety of locations to observe. …

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Pacific trade winds stall global surface warming … for now

The strongest trade winds have driven more of the heat from global warming into the oceans; but when those winds slow, that heat will rapidly return to the atmosphere causing an abrupt rise in global average temperatures.Heat stored in the western Pacific Ocean caused by an unprecedented strengthening of the equatorial trade winds appears to be largely responsible for the hiatus in surface warming observed over the past 13 years.New research published today in the journal Nature Climate Change indicates that the dramatic acceleration in winds has invigorated the circulation of the Pacific Ocean, causing more heat to be taken out of the atmosphere and transferred into the subsurface ocean, while bringing cooler waters to the surface.”Scientists have long suspected that extra ocean heat uptake has slowed the rise of global average temperatures, but the mechanism behind the hiatus remained unclear” said Professor Matthew England, lead author of the study and a Chief Investigator at the ARC Centre of Excellence for Climate System Science.”But the heat uptake is by no means permanent: when the trade wind strength returns to normal — as it inevitably will — our research suggests heat will quickly accumulate in the atmosphere. So global temperatures look set to rise rapidly out of the hiatus, returning to the levels projected within as little as a decade.”The strengthening of the Pacific trade winds began during the 1990s and continues today. Previously, no climate models have incorporated a trade wind strengthening of the magnitude observed, and these models failed to capture the hiatus in warming. Once the trade winds were added by the researchers, the global average temperatures very closely resembled the observations during the hiatus.”The winds lead to extra ocean heat uptake, which stalled warming of the atmosphere. Accounting for this wind intensification in model projections produces a hiatus in global warming that is in striking agreement with observations,” Prof England said.”Unfortunately, however, when the hiatus ends, global warming looks set to be rapid.”The impact of the trade winds on global average temperatures is caused by the winds forcing heat to accumulate below surface of the Western Pacific Ocean.”This pumping of heat into the ocean is not very deep, however, and once the winds abate, heat is returned rapidly to the atmosphere” England explains.”Climate scientists have long understood that global average temperatures don’t rise in a continual upward trajectory, instead warming in a series of abrupt steps in between periods with more-or-less steady temperatures. Our work helps explain how this occurs,” said Prof England.”We should be very clear: the current hiatus offers no comfort — we are just seeing another pause in warming before the next inevitable rise in global temperatures.”Story Source:The above story is based on materials provided by University of New South Wales. Note: Materials may be edited for content and length.

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Optogenetic toolkit goes multicolor: Seeing brain functions with light-sensitive proteins

Optogenetics is a technique that allows scientists to control neurons’ electrical activity with light by engineering them to express light-sensitive proteins. Within the past decade, it has become a very powerful tool for discovering the functions of different types of cells in the brain.Most of these light-sensitive proteins, known as opsins, respond to light in the blue-green range. Now, a team led by MIT has discovered an opsin that is sensitive to red light, which allows researchers to independently control the activity of two populations of neurons at once, enabling much more complex studies of brain function.”If you want to see how two different sets of cells interact, or how two populations of the same cell compete against each other, you need to be able to activate those populations independently,” says Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT and a senior author of the new study.The new opsin is one of about 60 light-sensitive proteins found in a screen of 120 species of algae. The study, which appears in the Feb. 9 online edition of Nature Methods, also yielded the fastest opsin, enabling researchers to study neuron activity patterns with millisecond timescale precision.Boyden and Gane Ka-Shu Wong, a professor of medicine and biological sciences at the University of Alberta, are the paper’s senior authors, and the lead author is MIT postdoc Nathan Klapoetke. Researchers from the Howard Hughes Medical Institute’s Janelia Farm Research Campus, the University of Pennsylvania, the University of Cologne, and the Beijing Genomics Institute also contributed to the study.In living colorOpsins occur naturally in many algae and bacteria, which use the light-sensitive proteins to help them respond to their environment and generate energy.To achieve optical control of neurons, scientists engineer brain cells to express the gene for an opsin, which transports ions across the cell’s membrane to alter its voltage. Depending on the opsin used, shining light on the cell either lowers the voltage and silences neuron firing, or boosts voltage and provokes the cell to generate an electrical impulse. This effect is nearly instantaneous and easily reversible.Using this approach, researchers can selectively turn a population of cells on or off and observe what happens in the brain. However, until now, they could activate only one population at a time, because the only opsins that responded to red light also responded to blue light, so they couldn’t be paired with other opsins to control two different cell populations.To seek additional useful opsins, the MIT researchers worked with Wong’s team at the University of Alberta, which is sequencing the transcriptomes of 1,000 plants, including some algae. (The transcriptome is similar to the genome but includes only the genes that are expressed by a cell, not the entirety of its genetic material.)Once the team obtained genetic sequences that appeared to code for opsins, Klapoetke tested their light-responsiveness in mammalian brain tissue, working with Martha Constantine-Paton, an MIT professor of brain and cognitive sciences and of biology, a member of the McGovern Institute, and an author of the paper. …

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Discovery May Lead to New Drugs for Osteoporosis

Scientists at Washington University School of Medicine in St. Louis have discovered what appears to be a potent stimulator of new bone growth. The finding could lead to new treatments for osteoporosis and other diseases that occur when the body doesn’t make enough bone.Osteoporosis affects 55 percent of Americans age 50 and older. Of that age group, one in three women and one in 12 men are believed to have osteoporosis, a condition responsible for millions of fractures each year, mostly involving the hips, wrist or lower back vertebrae.”We have been looking for new ways to stimulate bone formation,” said principal investigator Fanxin Long, PhD. “The tools we already have are very good at slowing the breakdown of bone, but we need better ways to stimulate new bone growth.”Studying mice, Long focused on a pathway involved in bone formation. The so-called WNT proteins carry messages into cells and regulate embryonic and adult tissue in mammals, including humans. The WNT proteins enter cells from the outside and then can activate multiple pathways inside those cells.Long’s team reports Jan. 30 in the journal that a specific member of the WNT family of proteins dramatically enhances bone formation, and it works through a mechanism that has not been well-studied in bone before.It’s called the mTOR pathway, and it interprets a cell’s surrounding environment, and nutritional and energy status.”By analyzing that information, mTOR can determine whether a cell should go into a mode to make lots of stuff, like proteins or, in this case, new bone,” explained Long, a professor of orthopaedic surgery. “Bone formation is an energetically expensive process, so it makes sense that some regulator would tell a cell whether there is sufficient energy and material to manufacture new bone.”Long and his colleagues studied mice that made either normal levels or an extra amount of WNT proteins. They found that a particular WNT protein, WNT7B, is a potent stimulator of bone formation in mice. …

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Genes linked to being right- or left-handed identified

Sep. 12, 2013 — A genetic study has identified a biological process that influences whether we are right handed or left handed.Scientists at the Universities of Oxford, St Andrews, Bristol and the Max Plank Institute in Nijmegen, the Netherlands, found correlations between handedness and a network of genes involved in establishing left-right asymmetry in developing embryos.’The genes are involved in the biological process through which an early embryo moves on from being a round ball of cells and becomes a growing organism with an established left and right side,’ explained first author William Brandler, a PhD student in the MRC Functional Genomics Unit at Oxford University.The researchers suggest that the genes may also help establish left-right differences in the brain, which in turn influences handedness.They report their findings in the open-access journal PLOS Genetics.Humans are the only species to show such a strong bias in handedness, with around 90% of people being right-handed. The cause of this bias remains largely a mystery.The researchers, led by Dr Silvia Paracchini at the University of St Andrews, were interested in understanding which genes might have an influence on handedness, in order to gain an insight into the causes and evolution of handedness.The team carried out a genome-wide association study to identify any common gene variants that might correlate with which hand people prefer using.The most strongly associated, statistically significant variant with handedness is located in the gene PCSK6, which is involved in the early establishment of left and right in the growing embryo.The researchers then made full use of knowledge from previous studies of what PCSK6 and similar genes do in mice to reveal more about the biological processes involved.Disrupting PCSK6 in mice causes ‘left-right asymmetry’ defects, such as abnormal positioning of organs in the body. They might have a heart and stomach on the right and their liver on the left, for example.The researchers found that variants in other genes known to cause left-right defects when disrupted in mice were more likely to be associated with relative hand skill than you would expect by chance.While the team has identified a role for genes involved in establishing left from right in embryo development, William Brandler cautioned that these results do not completely explain the variation in handedness seen among humans. He said: ‘As with all aspects of human behaviour, nature and nurture go hand-in-hand. The development of handedness derives from a mixture of genes, environment, and cultural pressure to conform to right-handedness.’

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The eyes have it: How organic mercury can interfere with vision

Sep. 11, 2013 — More than one billion people worldwide rely on fish as an important source of animal protein, states the United Nations Food and Agriculture Organization. And while fish provide slightly over 7 per cent of animal protein in North America, in Asia they represent about 23 per cent of consumption.Humans consume low levels of methylmercury by eating fish and seafood. Methylmercury compounds specifically target the central nervous system, and among the many effects of their exposure are visual disturbances, which were previously thought to be solely due to methylmercury-induced damage to the brain visual cortex. However, after combining powerful synchrotron X-rays and methylmercury-poisoned zebrafish larvae, scientists have found that methylmercury may also directly affect vision by accumulating in the retinal photoreceptors, i.e. the cells that respond to light in our eyes.Dr. Gosia Korbas, BioXAS staff scientist at the Canadian Light Source (CLS), says the results of this experiment show quite clearly that methylmercury localizes in the part of the photoreceptor cell called the outer segment, where the visual pigments that absorb light reside.”There are many reports of people affected by methylmercury claiming a constricted field of vision or abnormal colour vision,” said Korbas. “Now we know that one of the reasons for their symptoms may be that methylmercury directly targets photoreceptors in the retina.”Korbas and the team of researchers from the University of Saskatchewan including Profs. Graham George, Patrick Krone and Ingrid Pickering conducted their experiments using three X-ray fluorescence imaging beamlines (2-ID-D, 2-ID-E and 20-ID-B) at the Advanced Photon Source, Argonne National Laboratory near Chicago, US, as well as the scanning X-ray transmission beamline (STXM) at the Canadian Light Source in Saskatoon, Canada.After exposing zebrafish larvae to methylmercury chloride in water, the team was able to obtain high-resolution maps of elemental distributions, and pinpoint the localization of mercury in the outer segments of photoreceptor cells in both the retina and pineal gland of zebrafish specimens. The results of the research were published in ACS Chemical Biology under the title “Methylmercury Targets Photoreceptor Outer Segments.”Korbas said zebrafish are an excellent model for investigating the mechanisms of heavy metal toxicity in developing vertebrates. …

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Pumping draws arsenic toward a big-city aquifer

Sep. 11, 2013 — Naturally occurring arsenic pollutes wells across the world, especially in south and southeast Asia, where an estimated 100 million people are exposed to levels that can cause heart, liver and kidney problems, diabetes and cancer. Now, scientists working in Vietnam have shown that massive pumping of groundwater from a clean aquifer is slowly but surely drawing the poison into the water. The study, done near the capital city of Hanoi, confirms suspicions that booming water usage there and elsewhere could eventually threaten millions more people.The study appears in the current issue of the journal Nature.”This is the first time we have been able to show that a previously clean aquifer has been contaminated,” said lead author Alexander van Geen, a geochemist at Columbia University’s Lamont-Doherty Earth Observatory. “The amount of water being pumped really dominates the system. Arsenic is moving.” The good news, he said: “It is not moving as fast as we had feared it might.” This will buy time — perhaps decades–for water managers to try and deal with the problem, he said.Arsenic is found in rocks across the world, but it seems to pollute groundwater only under specific conditions. The huge scale across south Asia came clear only in the 1990s, when researchers from universities, nonprofit agencies and governments started testing wells systematically. Van Geen has been working in the field for 13 years, and is leading a new collaborative effort in the region under the International Continental Scientific Drilling Program.Researchers link natural arsenic pollution in south Asia to vast amounts of sediment eroding off the Himalayan plateau into basins below, from Pakistan and India to China and Vietnam. The constant fresh supply reacts rapidly with local water, though the exact mechanisms of arsenic release have remained unclear, along with the potential effects of groundwater pumping. The new study clarifies some of the chemical processes, and shows clearly for the first time that human activity can widen the problem.Hanoi, like many metropolitan areas, is mushrooming in size, and using ever more groundwater. …

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Autoimmune disease strategy emerges from immune cell discovery

Sep. 9, 2013 — Scientists from UC San Francisco have identified a new way to manipulate the immune system that may keep it from attacking the body’s own molecules in autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and multiple sclerosis.The researchers, led by immunologist Mark Anderson, MD, PhD, a professor with the UCSF Diabetes Center, have discovered a distinctive type of immune cell called an eTAC, which puts a damper on immune responses.Anderson’s research team found that eTACs reside in lymph nodes and spleen in both humans and mice, and determined that they could be manipulated to stop the destruction of the pancreas in a mouse model of diabetes. The study appears in the September issue of the journal Immunity.Using green fluorescent protein (GFP) to highlight a key regulatory protein called AIRE, Anderson’s research team tracked down the rare eTACs and their role in a phenomenon known as peripheral tolerance, which helps prevent autoimmune disease throughout the body.The newly described immune cells are of a type known as dendritic cells, which make up less than 3 percent of the cells in the immune system. ETAC cells account for a small fraction of all dendritic cells, Anderson said.Dendritic cells already have been the focus of new cell therapies to treat cancer. These therapies, which include treatments evaluated in clinical trials at UCSF, have been used to prod dendritic cells to rev up a complementary class of immune cells, called T cells. Treatment causes the T cells to target cancer cells, which, despite being abnormal, would not otherwise be subjected to vigorous attack in the same way as foreign microbial invaders.However, eTAC cells have the opposite effect. Instead of priming T cells to do battle, eTACs counteract the overactive immune response in autoimmune diseases. Anderson’s team took advantage of this property to demonstrate that eTACs could prevent autoimmune diabetes in mice.By displaying “self” molecules to T cells that target them, and turning off these T cells for good, eTACs help the immune system tolerate the molecules naturally present within us, Anderson said.”The mouse model we are working with involves using T cells that normally attack the islet cells of the pancreas, specifically by recognizing a molecule called chromagranin A that is present on islet cells,” Anderson said. “But if the eTACs can get to the T cells first and display chromagranin A, they can prevent T cells from attacking the islets.”Anderson aims to exploit eTACs therapeutically by finding out how to grow them in large numbers outside the body. “We need to figure out how to grow a lot of these cells, to load them up with whatever molecule it is that we want to induce tolerance to, and then to load them back into a patient,” he said. …

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Recycled sewage water is safe for crop irrigation, study suggests

Sep. 9, 2013 — The first study under realistic field conditions has found reassuringly low levels of pharmaceuticals and personal care products (PPCPs) in crops irrigated with recycled sewage water, scientists reported in Indianapolis today at the 246th National Meeting & Exposition of the American Chemical Society (ACS).”The levels of pharmaceuticals and personal care products that we found in food crops growing under real-world conditions were quite low and most likely do not pose any health concern,” said Jay Gan, Ph.D., who led the study. “I think this is good news. These substances do not tend to accumulate in vegetables, including tomatoes and lettuce that people often eat raw. We can use that information to promote the use of this treated wastewater for irrigation.”Gan and colleagues at the University of California-Riverside launched the study because drought and water shortages in the American southwest and in other arid parts of the world are using water recycled from municipal sewage treatment plants to irrigate food crops as the only option.Water from toilets and sinks enters those facilities from homes and offices, and undergoes processing to kill disease-causing microbes and remove other material. Processing leaves that water, or “effluent,” from most sewage treatment plants clean enough to drink. Traditionally, however, sewage treatment plants simply discharge the water into rivers or streams. The effluent still may contain traces of impurities, including the remains of ingredients in prescription drugs, anti-bacterial soaps, cosmetics, shampoos and other PPCPs that are flushed down toilets and drains.Gan explained that concerns have arisen about the health and environmental effects of those residual PPCPs, especially over whether they might accumulate to dangerous levels in food crops. Previous studies on PPCPs in food crops were small in scale and conducted in laboratories or greenhouses. Gan said his team was the first to focus on 20 PPCPs in multiple crops under realistic field conditions.They chose eight vegetables that people often eat raw — carrots, bell peppers, tomatoes, cucumbers, lettuce, spinach, celery and cabbage. …

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Toward making people invisible to mosquitoes

Sep. 9, 2013 — In an advance toward providing mosquito-plagued people, pets and livestock with an invisibility cloak against these blood-sucking insects, scientists today described discovery of substances that occur naturally on human skin and block mosquitoes’ ability to smell and target their victims.Ulrich Bernier, Ph.D., who gave the talk, cited the pressing need for better ways to combat mosquitoes. Far from being just a nuisance, mosquitoes are more deadly to humans than any other animal. Their bites transmit malaria and other diseases that kill an estimated one million people around the world each year. In the United States, mosquitoes spread rare types of encephalitis, an inflammation of the brain. They also transmit heart worms to pet dogs and cats.”Repellents have been the mainstay for preventing mosquito bites,” said Bernier. “The most widely used repellant, DEET, is quite effective and has been in use for a long time. However, some people don’t like the feel or the smell of DEET. We are exploring a different approach, with substances that impair the mosquito’s sense of smell. If a mosquito can’t sense that dinner is ready, there will be no buzzing, no landing and no bite.”Female mosquitoes, which suck blood to obtain a protein needed to produce fertile eggs, can smell people from over 100 feet away. …

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Translating nature’s library yields drug leads for aids, cancer, Alzheimer’s disease

Sep. 9, 2013 — An ingredient in a medicinal tea brewed from tree bark by tribal healers on the South Pacific island of Samoa — studied by scientists over the last 25 years — is showing significant promise as a drug lead in the long-sought goal of eliminating the AIDS virus from its sanctuaries in the body and thus eradicating the disease, a scientist said.Speaking at the 246th National Meeting & Exhibition of the American Chemical Society (ACS), Paul A. Wender, Ph.D., described efficient new ways of making prostratin and related leads, as well as other drug candidates first discovered in sea creatures, that appear even more effective for AIDS and have applications for Alzheimer’s disease and cancer.In his presentation, Wender focused on fundamentally new approaches to some of the most serious unmet health challenges of our time. He is with Stanford University. They include the eradication of AIDS, developing medicines that stop the progression of Alzheimer’s disease and treating resistant cancer — the major cause of chemotherapy failure for most cancers.Wender leads a scientific team at Stanford University that first developed a way to make the tea ingredient, prostratin, in large amounts from readily available ingredients. He described how that initial synthesis broke down a major barrier to probing prostratin’s antiviral effects. Until then, scientists had to extract prostratin from the bark of the Samoan mamala tree, and only tiny and variable amounts were so obtained. Samoa is where another scientist, Paul Cox, in 1987 heard a native healer praise mamala bark tea as a remedy for viral hepatitis. It led scientists at the National Cancer Institute to analyze the bark and identify prostratin as a key ingredient. Wender’s synthesis of prostratin opened the door to research on the substance and enabled his team to change prostratin’s architecture.”We now have made synthetic variants of prostratin, called analogs, that are 100 times more potent than the natural product,” Wender said. …

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Toward treating disease the way artificial limbs replace the function of lost arms and legs

Sep. 9, 2013 — The vision for a new branch of medicine, inspired by the ancient field that began with peg legs and hand hooks, commanded the spotlight in a major address by its pioneer in Indianapolis today at the 246th National Meeting & Exposition of the American Chemical Society (ACS).Martin D. Burke, M.D., Ph.D., focused on the field he has named “molecular prosthetics,” after the small molecules that make up the ingredients in most drugs and the branch of medicine that involves artificial or prosthetic body parts.”Artificial limbs replace the function of an arm or leg that’s missing due to injury,” Burke said. “Some diseases occur because proteins in the body are missing or not working properly. Molecular prosthetics envisions treating those diseases with medicines that replace the functions of the missing proteins.”Burke described advances toward making molecular prosthetics a reality, including progress in developing a platform that would revolutionize the now-tedious processes of making or synthesizing the ingredients for those drugs. Burke, who is with the Howard Hughes Medical Institute and University of Illinois at Urbana-Champaign, delivered the “Kavli Foundation Emerging Leader in Chemistry Lecture” at the meeting.Burke and his team already have gained fame for improvements in the Suzuki-Miyaura cross-coupling reaction of boronic acids. Despite the obscure name, that Nobel Prize-winning reaction is one of the most important and widely used tools in organic chemistry. It is the basis for the manufacture of ingredients for medicines, plastics, perfumes, herbicides and other products. Burke’s team developed special building blocks that can be used in the reaction to make some small molecules in days instead of months or years. The building blocks are available commercially, and drug companies are using them in the search for new medicines.In the Kavli lecture, Burke described advances to simplify and speed up the synthesis of the small molecules needed for molecular prosthetics. …

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Yin-yang effect of sodium and chloride presents salt conundrum

Sep. 8, 2013 — Eat less salt’ is a mantra of our health-conscious times and is seen as an important step in reducing heart disease and hypertension.Too much salt in the diet — and specifically sodium — is widely acknowledged as a major risk factor for high blood pressure however, scientists have found that salt’s other oft-overlooked constituent chloride might also play an important role.A study by researchers at the University of Glasgow has revealed that low chloride levels in the blood is an independent indicator of mortality risk in people with hypertension. The role of chloride in hypertension has received little attention from scientists hitherto.After analysing data from almost 13,000 patients with high blood pressure, followed up over 35 years, the researchers found that low levels of chloride was associated with a higher risk of death and cardiovascular disease.The group with the lowest level of chloride in their blood had a 20% higher mortality rate compared to the other subjects. The results are published in the journal Hypertension.Dr Sandosh Padmanabhan of the Institute of Cardiovascular and Medical Sciences, said: “Sodium is cast as the villain for the central role it plays in increasing the risk of high blood pressure, with chloride little more than a silent extra in the background.”However, our study has put the spotlight on this under-studied chemical to reveal an association between low levels of chloride serum in the blood and a higher mortality rate, and surprisingly this is in the opposite direction to the risks associated with high sodium.”It is likely that chloride plays an important part in the physiology of the body and we need to investigate this further.”Chloride is already measured as part of routine clinical screening and so monitoring of chloride levels could easily be incorporated into clinical practice to identify individuals at high risk.Dr Padmanabhan added: “The results we see from this study are confounding against the knowledge that excess salt is a bad thing, yet higher levels of chloride in the blood seems to be an independent factor that is associated with lower mortality and cardiovascular risk. We seem to have entered a grey area here that requires further investigation.”It is too early to draw any conclusions about relating this finding to salt intake and diet. We need more research to establish exactly what the relationship between chloride and health risk is.”

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