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TOP 30 UNIVERSITIES AS PER – MHRD, GOVT OF INDIA FOR 2018
TOP 20 COLLEGES OF INDIA AS PER GOVT OF INDIA SURVEY – 2018
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ADHESION PROTEIN THAT HELPS BACTERIA STICK TO CELLS COULD HELP FIND NEW ANTIBIOTICS
NEWS EDITION
CARDIOVASCULAR RISK INCIDENCE PREDICTING BLOOD TEST DEVELOPED
THE DOWNFALL OF BACTERIA?
The shape, elongation, division and sporulation (SEDS) proteins are a large family of ubiquitous and essential transmembrane enzymes with critical roles in bacterial cell wall biology.
By Disha Padmanabha
A CELL-WALL BUILDING PROTEIN COULD CAUSE THE DOWNFALL OF BACTERIA The exact function of SEDS proteins was for a long time poorly understood, but now, a recent research by a team at the Harvard Medical School has revealed how it could make for an uncompromisable Achilles heel of most bacteria. The study has revealed that the prototypical SEDS family member RodA is a peptidoglycan polymerase—a role previously attributed exclusively to members of the penicillin-binding protein family. This discovery has thereby made RodA and other SEDS proteins promising targets for the development of next-generation antibiotics. “Our latest findings reveal the molecular structure of RodA and identify targetable spots where new antibacterial drugs could bind and subvert its work,” said study senior investigator Andrew Kruse, associate professor of biological chemistry and molecular pharmacology at Harvard Medical School.
The researchers mapped RodA’s molecular structure and found that it included an unusual cavity on its outer edge. And where there’s a gap – in anything, really – sooner or later someone will find an object to fill it. To test the limits of RodA’s apparent weak spot, the scientists set up experiments using two species drawn from the two basic bacterial domains – gram-negative and gram-positive. In both cases, they found that making even small changes to the shape of the cavity caused the bacteria to distort, swell, and eventually burst. For drug developers, the result is potentially great news.
microbiology and immunobiology at Harvard Medical School. “A chemical compound—an inhibitor— that binds to this pocket would interfere with the protein’s ability to synthesize and maintain the bacterial wall,” Rudner said. “That would, in essence, crack the wall, weaken the cell and set off a cascade that eventually causes it to die.” Additionally, because the protein is highly conserved across all bacterial species, the discovery of an inhibiting compound means that, at least in theory, a drug could work against many kinds of harmful bacteria. “This highlights the beauty of super-basic scientific discovery,” said co-investigator Thomas Bernhardt, professor of microbiology and immunobiology at Harvard Medical
School. “You get to the most fundamental level of things that are found across all species, and when something works in one of them, chances are it will work across the board.” The success of this “roundabout” approach, researchers said, circumvents a significant hurdle in field of structural biology and can open the doors toward defining the structures of many more newly discovered proteins. “These insights underscore the importance of creative crosspollination among scientists from multiple disciplines and departments,” said study first author Megan Sjodt, a research fellow in biological chemistry and molecular pharmacology at Harvard Medical School. “We believe our results set the stage for subsequent work toward the discovery and optimization of new classes of antibiotics.”
“What makes us excited is that this protein has a fairly discrete pocket that looks like it could be easily and effectively targeted with a drug that binds to it and interferes with the protein’s ability to do its job,” said study co-senior author David Rudner, professor of
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Vol. 02 NO 16
April 17th, 2018.
TOP 30 UNIVERSITIES AS PER – MHRD, GOVT OF INDIA FOR 2018
By Shekhar Suman
MHRD, Govt of India under National Institutional Ranking Framework has released a list of Top 100 Universities with rank. Listed below are names and scores of Top 30 Uni-
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versities of India. For all PhD Admissions, Msc Admissions, B.tech Admissions, B.Sc Admissions, M.Tech Admissions.
Vol. 02 NO 16
April 17th, 2018.
TOP 20 COLLEGES OF INDIA AS PER GOVT OF INDIA SURVEY – 2018
As per survey done by NIRF, Government of India for the year 2018, listed below are top 20 colleges of India. List of top 20 colleges has been released with their score. Names of Top Colleges all across India can be found
below. In the Top 5 list are 3 colleges from Delhi – Miranda House, St. Stephen`s College & Hindu College each occupying 1st, 2nd & 4th position respectively.
LIVER REGENERATION THROUGH TELOMERASE REPOPULATION Myriad genetic and epigenetic alterations are required to drive normal cells toward malignant transformation. These somatic events commandeer many signaling pathways that cooperate to endow aspiring cancer cells with a full range of biological capabilities needed to grow, disseminate and ultimately kill its host. Telomeres are nucleoprotein structures that protect the ends of eukaryotic chromosomes and are particularly vulnerable due to progressive shortening during each round of DNA replication and, thus, a lifetime of tissue renewal places the organism at risk for increasing chromosomal instability. Telomere dysfunction can produce the opposing pathophysiological states of degenerative aging or cancer with the specific outcome dictated by the integrity of DNA damage checkpoint responses. Hepatocytes are replenished gradually during homeostasis and robustly after liver injury. In adults, new hepatocytes originate from the existing hepatocyte pool, but the cellular source of renewing hepatocytes remains unclear. Now, Stanford scientists have identified a subset of hepatocytes that expresses high levels of telomerase and show that this hepatocyte subset repopulates the liver during homeostasis and injury. “The liver is a very important source of human disease,” said professor of medicine Steven Artandi, MD, PhD. “It’s critical to understand the cellular mechanism by which the liver renews itself. We’ve found that these rare, proliferating cells are spread throughout the organ, and that they are necessary to enable the liver to replace damaged cells. We believe that it is also likely that these cells could give rise to liver cancers when their regulation goes awry.”
By Shekhar Suman
“These rare cells can be activated to divide
and form clones throughout the liver,” said Artandi, who holds the Jerome and Daisy Low Gilbert Professorship in Biochemistry. “As mature hepatocytes die off, these clones replace the liver mass. But they are working in place; they are not being recruited away to other places in the liver. This may explain how the liver can quickly repair damage regardless of where it occurs in the organ.” In the course of their investigation, the team found that, in mice, about 3-5 percent of all liver cells express unusually high levels of telomerase. During regular cell turnover or after the liver was damaged, these cells proliferate in place to make clumps of new liver cells. The fact that these stem cells express fewer metabolic genes might be one way to protect the cells from the daily grind faced by their peers, and to limit the production of metabolic byproducts that can damage DNA. “This may be one way to shelter these important cells and allow them to pass on a more pristine genome to their daughter cells,” Artandi said. “They are not doing all the ‘worker bee’ functions of normal hepatocytes.” When Lin engineered the telomerase-expressing hepatocytes to die in response to a chemical signal and gave the mice with a liver-damaging chemical, he found that those animals in which the telomerase cells had been killed exhibited much more severe liver scarring than those in which the cells were functional. “You could imagine developing drugs that protect these telomerase-expressing cells, or ways to use cell therapy approaches to renew livers,” said Artandi. “On the cancer side, I think that these cells are very strong candidates for cell of origin. We are finally beginning to understand how this organ works.” By Disha Padmanabha
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Scientists Coax Oil-Gulping Bacteria into Cleaning Spills Bioremediation for degradation of hydrocarbons is a widely used alternative for the recovery of contaminated sites. Now, researchers at the INRS in Canada have isolated the key enzymes that a oil-hungry bacterium, Alcanivorax borkumensis, uses in order to clean oil samples in lab. These enzymes give it the special ability to use hydrocarbons as a source of energy. This microorganism exists in every ocean and multiplies quickly where there are high concentrations of oil. In fact, this bacteria is likely responsible for some of the natural degradation of ocean spills, but researchers want to amplify this effect to speed up the clean up process. The enzymes in the bacteria do the work and in particular the hydroxylases are very effective and resistant to chemical conditions. Since its remedial potential had not been assessed, the team characterized the enzymes produced and revealed thr presence of hydroxylases that are resistant to chemical conditions and far more effective in promoting hydrocarbon degradation than those found in other species. When applied to samples of contaminated
soils, purified enzymes from A. borkumensis effectively degraded over 80 percent of some hydrocarbon compounds. The degradation efficiency for different concentrations of petroleum hydrocarbon substrates was significant, reaching 73.75 percent for 5000 ppm of hexadecane, 82.80 percent for 1000 ppm of motor oil, 64.70 percent for 70 ppm of benzene-toluene-xylene and 88.52 percent for 6000 ppm of contaminated soil. “The degradation of hydrocarbons using the crude enzyme extract is really encouraging and reached over 80 percent for various compounds,” says Satinder Kaur Brar, lead researcher on the study. “The process is effective in removing benzene, toluene, and xylene, and has been tested under a number of different conditions to show that it is a powerful way to clean up polluted land and marine environments.” The researchers plan to continue studying how A. borkumensis metabolizes these hydrocarbons, and figure out how they might be put to work cleaning up real-life oil spills.
By Disha Padmanabha
Scientists Grow First Adult-like Cardiac Tissue from Patient-Specific Stem Cells
Cardiac tissues generated from human induced pluripotent stem cells (iPSCs) can serve as platforms for patient-specific studies of physiology and disease. But then, the predictive power of these models is presently limited by the immature state of the cells. Now however, Columbia University researchers have developed a radically new approach to growing in the lab adult-like human heart muscle from blood-derived human induced pluripotent stem cells (iPSCs), over only four weeks of bioreactor cultivation. “Many of the ongoing efforts—including those from our lab—have been biomimetic in nature, trying to recapitulate the known events present during native development,” says the study’s senior author Gordana Vunjak-Novakovic, University Professor, The Mikati Foundation Professor at Columbia Engineering, and professor of medicine at Columbia University Vagelos College of Physicians and Surgeons. “Because these efforts have been limited in how much maturation can be achieved, we decided to try something totally new: to explore the concept of accelerated development. It took a lot of creative thinking and clever engineering by the whole team across both campuses of Columbia University to develop the model we now have, a highly matured, patient-specific heart muscle that can be used for studies of heart development, physiology, disease, and responses to drugs.” Stem cells are an especially awesome type of undifferentiated cells that are able to change into specialized cells. The team got their hands on some by simply taking a blood sample. From this, they derived early-stage cardiac muscle cells, also known as cardiomyocytes and then cultured them using their new revolutionary method. This approach allowed the researchers to nurture the cells to maturity in just four weeks, compared to the usual nine months. The results showed that intensity-trained tissues grown from early-stage hiPS-CMs matured quickly to display “remarkably organized ultrastructure,” and structural feaBen Waldau says.
STEM CELL DERIVED MINI BRAIN THAT ENGENDERS BLOOD VESSELS The human cerebral cortex defines us as who we are. Its development and function underlie complex human cognitive behavior, while its malfunction or degeneration causes countless neurological and psychiatric diseases. Additionally, shielded by by our thick skulls and swaddled in layers of protective tissue, the human brain is extremely difficult to observe in action. And in both these cases- emerges a saviour- the mini brain. Lab-grown miniature brains are poised to shake up drug testing for everything from Alzheimer’s disease to Zika. Reported early last year, each bundle of human brain cells is so tiny that it could fit on
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the head of a pin. With induced pluripotent stem cells (iPSCs) derived from a readily-accessible skin sample from patients, it’s possible to generate three-dimensional balls of cells that mimic particular parts of the brain’s anatomy. But then, as with any new tech, there is always room for improvement. One thing that most mini-brains lack is their own system of blood vessels, or vasculature. “The whole idea with these organoids is to one day be able to develop a brain structure the patient has lost made with the patient’s own cells,” UC Davis vascular neurosurgeon
The breakthrough could allow the brains to survive for longer, thanks to the vital oxygen and nutrients supplied by the vessels, and could encourage them to keep growing. Using brain membrane cells taken from one of his patients during a routine surgery, the team coaxed them first into stem cells, then some of them into the endothelial cells that line blood vessels’ insides. The stem cells they grew into brain balls, which they incubated in a gel matrix coated with those endothelial cells. After incubating for three weeks, they took
tures characteristic of adult heart tissue, the team states. Such features included the physiological length of the sarcomeres, density of mitochondria, the presence of transverse tubules, and the switch to oxidative metabolism. “The increasing contractile demands induced the adult-like cardiac morphology that is necessary for high force generation in early-stage intensity-trained tissues,” the team writes. “The cell size increased (an indicator of physiological hypertrophy) and both cells and nuclei were elongated (an indicator of maturation). The sarcomere length reached 2.2 μm, a similar value to that of adult human ventricular myocytes.” The team is now extending their study into broader aspects of disease modeling to get a better understanding of the mechanistic basis of cardiac disease and cardiotoxicity induced by drugs used to treat other organ systems. Their work could facilitate discovery of new therapeutic targets and lead to new cardioprotective or curative treatment modalities. This ongoing research is part of the “organs on a chip” project funded by the National Institutes of Health, which uses multi-tissue platforms that include the adult heart muscle referenced in this paper as well as bone, liver, vasculature, skin, and solid tumors. “The resulting engineered tissue is truly unprecedented in its similarity to functioning human tissue,” said Seila Selimovic, director of the NIBIB (National Institute of Biomedical Imaging and Bioengineering) Tissue Chips program, within the National Institutes of Health that funded this research. “The ability to develop mature cardiac tissue in such a short time is an important step in moving us closer to having reliable human tissue models for drug testing.” The better the engineered tissues emulate the human heart, the better they can predict the effects that drugs or environmental factors have on the actual heart tissue of a patient. Having a reliable human tissue model would help make drug development significantly faster, safer, and cheaper.” By Disha Padmanabha
a single organoid and transplanted it into a tiny cavity carefully carved into a mouse’s brain. Two weeks later the organoid was alive, well—and, critically, had grown capillaries that penetrated all the way to its inner layers. These so-called brain balls are the first to become vascularised (meaning they’re the first to sprout vessels), with previous experiments resulting in mouse blood cells infiltrating the small cerebrums. However, scientists still aren’t certain if the blood this network of vessels carries is human or rodent. By Disha Padmanabha
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Scientists Unveil New Bioengineering Tech to Manufacture Complex Medicines Microbial biosynthesis of plant natural products from simple building blocks is a promising approach toward scalable production and modification of high-value compounds. Now, researchers describe a bioengineering process in which brewer’s yeast, along with engineered genes from opium poppies and rats, is used to produce a non-narcotic cough suppressant with potential anticancer properties. Stanford researchers inserted 25 foreign genes, which came from the opium poppy, other plants and even rats, into the onecelled fungus. All those genes were recipes for enzymes: protein machines that, working together, can build complex substances from simple starting materials. The researchers also modified some of the plant, rat and yeast genes, as well as the medium in which the yeast proliferates, to help everything work better together. The result was an 18,000-fold improvement in noscapine output, compared with what could be obtained by just inserting the plant and rat genes into yeast.
Stanford University bioengineering professor Christina Smolke said: “This is a technology that’s going to change the way we manufacture essential medicines.” Noscapine’s cough-suppressing capability was discovered in 1930. The drug was also found to be a potential oncology therapy during preclinical trials, where it exhibited less impact on healthy cells than currently available chemotherapy. “Traditionally, we’ve gotten our medicines from the natural world, mainly from plants,” Smolke told me when I interviewed her about the study. “But the plants’ molecular assembly lines have evolved to optimize the plants’ survival, not to churn out buckets of one substance we humans want to get our hands on. Plus, we’re putting them into our yeast strain, which is foreign turf. A yeast cell and a poppy cell have a lot in common, but in some respects they’re as different as Earth and Mars.” “It’s as if we’re grabbing a couple dozen
By Disha Padmanabha
soldiers from different units, deploying them on Mars, and telling each of them, ‘Now, I want you to get some serious work done here, and I want you to work with these other soldiers you haven’t worked with before,’” Smolke continued. “Good luck with that. We modified them so they’d get along with one another better on this new planet.” The only viable source of noscapine is opium poppies. Many tons of noscapine are extracted annually from the plant, which takes a full year to mature. While noscapine itself is harmless, the poppies’ illicit potential requires costly controls and restrictive regulations. Additionally, naturally occurring noscapine must be thoroughly separated from numerous molecular companions, narcotic and otherwise, that don’t occur in yeast. The yeast Smolke’s group bioengineered
can spew out substantial amounts of noscapine in three or four days. The investigators achieved this result by stitching three separate sections of the noscapine biosynthesis pathway into a single yeast strain. They used CRISPR, a gene-editing tool, to alter inserted genes so that the enzymes for which they coded would work most efficiently amid the exotic acidity, osmotic character and chemical composition of their new home. They also souped up the yeast’s production of a chemical whose levels would have otherwise been too low to sustain robust noscapine production. “We’re no longer limited to what nature can make,” Smolke said. “We’re moving to an age where we can borrow nature’s medicine-manufacturing processes and, using genetic engineering, build miniature living factories that make what we want.”
Abundant Giant Virus in Sea Captured and Characterized Viruses are the most abundant biological entities on the planet and there are typically millions of virus particles in each milliliter of marine or fresh waters that are estimated to kill about 20% of the living biomass each day in surface marine waters. Most of these viruses are tiny, often 10 or 100 times smaller than bacteria. However, a few reach a similar size and complexity to bacteria, and so stand out as relative giants. Relative to other viruses, Giant Viruses have much more DNA in their genome, which in turn provides the genetic template to produce the proteins that allow viruses to reproduce largely independently of its host. Typically, more than half of the genes encoded by Giant Viruses have no evident similarity to genes from other viruses or cellular life. Sequencing DNA from ocean water suggests that Giant Viruses are abundant and ecologically important; yet, few have been isolated from the microbes that they infect. Without being able to study Giant Viruses in the laboratory, little can be known about their biology, the way they infect their hosts, and their broader influence on aquatic life. Motivated by the lack of ecologically relevant giant-virus isolates- Bodo saltans virus, the first isolated representative of the most abundant giant viruses in the sea, has now been unveiled by researchers at the University of British Columbia. The Bodo saltans virus (BsV), whose genome weighs in at 1.39 million bases of DNA, is one of the largest giant viruses ever isolated, and the largest known to infect zo-
oplankton. It is found to possess an arsenal of toxins and DNA cutting enzymes, which likely interfere with other viruses trying to replicate inside the host. During an infection, BsV maneuvers in direction of the rear of the host cell and releases its viral genome. It seems on observation that as BsV advanced it stole genetic equipment from the host to assist in the an infection course of. BsV would not carry switch RNA (tRNA), half of the replication equipment all different big viruses carry. It does, nevertheless, carry tRNA restore genes, making it doubtless that the virus makes use of the host’s personal tRNA throughout an infection. Again, these genes seem to have been coopted by the virus straight from the host. More than 10 per cent of BsV’s genome encodes the identical group of proteins which are doubtless concerned in combating the host’s antiviral system. This suggests that the virus is engaged in an evolutionary arms race with its host, and could offer on explanation of how the genomes of giant viruses could reach their impressive complexity.
By Disha Padmanabha Christoph Deeg and Curtis Suttle isolated Bodo saltans virus in samples from UBC’s Nitobe Memorial Garden.
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Double Attack Antibody Picks on Viruses from Two Sides Immunoglobulin A (IgA) plays an important role in protecting our mucosal surfaces from viral infection, in maintaining a balance with the commensal bacterial flora, and in extending maternal immunity via breast feeding. Working together with scientists from the US, researchers at the University of Zurich have now discovered a new aspect of how the flu virus interacts with antibodies in the lungs. “This was a completely unexpected and unforeseen finding,” says Lars Hangartner, former professor at the Institute of Medical Virology of UZH. “We found that antibodies called IgAs, which are commonly found on mucosal surfaces, can actually protect us from infections in two different ways,” adds the head of the study, who now works at The Scripps Research Institute in the USA. The University of Zurich (UZH) team has discovered a new mechanism that could potentially be used to develop better flu vaccines and more effective drugs. Antigens provide the immune system with a kind of blueprint that allows it to recognize flu viruses and start the production of antibodies as soon as it encounters them again. However, current vaccines stimulate the production of another type of antibodies: Immunoglobulin G (IgG).
The team studied different kinds of antibodies in cell cultures to find out which ones were most potent against the flu virus. They found that a subtype called IgA1, which has a special tail at one end that contains sialic acids, was the most effective. It was found through investigation that this tail blocks the part of the virus that allows it to attach to the cells it wants to infect. This suggests that the IgA1 antibody works through two different types of immune activity. Firstly, through acquired immunity, which is traditionally associated with antibodies that specifically recognize pathogens. And secondly, through innate immunity via the sialic acids at the other end of the molecule, which is more of a non-specific, broad-ranging attack. IgA antibodies thus attach themselves to flu viruses in two places at once. The team believes that this study could help improve the effectiveness of flu vaccinations and drugs. Since IgAs are notoriously hard to work with, Hangartner believes future research should focus on developing antibodies that are easier to produce and can be tested in mice. His idea is to graft the tail of the IgA1 onto an IgG-type antibody, which is much easier
By Disha Padmanabha Immune cells produce certain antibodies that attack influenza viruses from two sides. (Image: iStock/selvanegra)
to handle. “It would combine the best of both worlds and give us a molecule that’s more effective and hardy, and that ultimately may be
very useful when it comes to fighting the flu,” adds the immunologist.
Adhesion Protein that Helps Bacteria Stick to Cells Could Help Find New Antibiotics
Many pathogenic bacteria, including Streptococcus gordonii, possess a pathway for the cellular export of a single serine-rich-repeat protein that mediates the adhesion of bacteria to host cells and the extracellular matrix. Now, researchers at Harvard Medical School, the University of California–San Francisco, and the University of Georgia have described how the protein that allows strep and staph bacteria to stick to human cells is prepared and packaged. An important class of extracellular molecules produced by pathogenic bacteria are adhesins, proteins that enable bacteria to adhere to host cells. For unknown reasons, the SRR (serine-rich-repeat) adhesins of Staphylococcus and Streptococcus bacteria- pathogens that can be involved in serious infections such as bacterial meningitis, bacterial pneumonia and pericarditis- are transported through a secretion pathway that is similar to the standard system, but dedicated solely to adhesin. Tom Rapoport, a professor at Harvard Medical School who oversaw the new study, wanted to understand what exactly these ded-
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icated molecular supply chains were doing. “I was intrigued by the fact that there is a second secretion system in some bacteria that is separate from the canonical secretion system and is just dedicated to the secretion of one protein,” he said. “There is a whole machinery, and it’s only doing one thing.” The researchers found that in order to be transported, the adhesin protein needed to be modified with specific sugars by three enzymes acting in a specific sequence. These sugar modifications stabilize the protein and enhance its stickiness to target cells. The experiments the team carried out indicated that two proteins in the adhesin-specific pathway, whose function had previously been mysterious, seemed to be able to bind to these sugars, presumably enabling them to carry the adhesin to the cell membrane where adhesin’s dedicated exit channel is located. “It’s a complicated system because it involves protein modification, chaperone activity and membrane targeting, so we encoun-
By Disha Padmanabha
tered a lot of challenges,” said Yu Chen who led the investigation. The reason that these bacteria use this separate export pathway for adhesins remains elusive. But because this pathway is unique
to strep and staph bacteria, the new understanding of its components could help researchers develop highly targeted antibiotics to treat infections caused by these bacteria in the future.
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Space Salad: Scientists Grow Plants in Space-like Conditions at Antarctica Gardening in microgravity will lettuce go into space- probably even make it to Mars without a worry. The ability to grow plants in limited conditions is aessential for the future of deep-space exploration. A critical component of future, human exploration to worlds unknown, will be the supply of edible food for crewmembers. To develop innovations in cultivating food in closed-loop systems becomes integral to future missions. Scientists at Germany’s Neumayer Station III in Antarctica have just harvested a crop of vegetables grown in the unlikely location of their Antarctic lab. The haul consisted of 3.6 kg of salad greens, 18 cucumbers, and 70 radishes. Cucumbers, radishes and lettuce are just some of the green delights that have been thriving in the experimental EDEN-ISS greenhouse in Antarctica. The project follows in the footsteps of successful US operations cultivating crops in the harsh climate. In addition to the veggies they just harvested, the scientists also planted strawberries, bell peppers, and a number of herbs. By May, DLR says they expect to be able to get about 10 pounds of produce per week. Despite temperatures in Antarctica falling below -20 degrees Celsius (-4 F) and the sun barely coming above the horizon, the first harvest from the project led by the German Aerospace Center (DLR) demonstrates how astronauts on the moon and Mars could be
supplied with fresh food in the future. This mission worked to test just how astronauts will be able to sustain themselves while in space. There will be manned missions to Mars and the moon that will seek to colonize both worlds. EDEN ISS is a consortium of European, American, and Canadian experts in human spaceflight and CEA. “It was special to have the first fresh salad of the Antarctic,” said station manager Bernhard Gropp in a statement. “It tasted as if we had harvested it fresh in the garden.” Located at the Neumeyer-Station III, the greenhouse defies the Arctic winter with its state-of-the-art technology; pipes supply sufficient water, lamps provide the right light, and filters and nozzles provide the right mixture of air to promote growth. Large water tanks installed in the floor are filled with melted, filtered, and purified ice from the station. Water is then added to a “special nutrient solution” that is automatically sprayed on the plants every five to 10 minutes, a process called aeroponics. Bottles of carbon dioxide were shipped along with the container to provide the plants with ideal air. The air is then filtered by a UV radiation system similar to the closed-circuit system onboard the ISS. In a land of extreme light cycles, the crew needed to make sure plants got a “blue and red light cocktail”. A customized water-cooled
NOVEL RNA VACCINE COULD FREE PLANTS FROM PESTICIDE USE Pesticides are the only toxic substances released intentionally into our environment to kill living things. This includes substances that kill weeds (herbicides), insects (insecticides), fungus (fungicides), rodents (rodenticides), and others. The use of toxic pesticides to manage pest problems has become a common practice around the world. It is difficult to find somewhere where pesticides aren’t used- from the can of bug spray under the kitchen sink to the airplane crop dusting acres of farmland, our world is filled with pesticides. In addition, pesticides can be found in the air we breathe, the food we eat, and the water we drink. Now, an international team led by researchers from the University of Helsinki and the French National Centre for Scientific Research has created a new method to produce a vaccine that triggers RNA interference—an innate defense mechanism of plants, animals and other eukaryotic organisms against pathogens. “A new approach to plant protection involves vaccinating plants against pathogens with double-stranded RNA molecules that can be sprayed directly on the leaves,” explains Dr Minna Poranen of the Molecular and Integrative Biosciences Research Programme at the University of Helsinki’s Faculty of Biological and Environmental Sciences. “The challenge in developing RNA-based vaccines to protect plants has involved
the production of RNA molecules. Double-stranded RNA molecules have been produced through chemical synthesis, both as drug molecules and for research purposes, but such production methods are inefficient and expensive for plant protection,” Poranen states. Emerging technologies for crop protection include the external treatment of plants with double-stranded (ds) RNA to trigger RNA interference. However, using this method in greenhouses and fields depends on the dsRNA quality, stability and efficient large-scale production. In this particular study, scientists designed a vaccine that uses RNA interference, which is an innate defence mechanism of plants, animals and other eukaryotic organisms against pathogens. This vaccine can be targeted to the chosen pathogen by using RNA molecules which share sequence identity with the pest’s genes and prevents their expression; thereby not influencing the expression of genes in the protected plant in anyway. Together with researchers at the CNRS, the group has demonstrated the efficacy of RNAbased vaccines produced using the new method against plant virus infections. This new method will enable the effective production of RNA-based vaccines and promote the development and adoption of RNAbased plant protection methods.
By Disha Padmanabha
LED system allows for each light to be individually controlled by a computer. Plants are illuminated for 16 hours and get a standard eight hours of beauty rest without light. For researchers living in Antarctica, the prospect of fresh vegetables will be an exciting change from stations’ usual dependency on planes to deliver fresh food, and reliance on frozen or dried food otherwise. For interplanetary explorers, the ability to grow food on others worlds could mean the difference between life and death.
NASA estimates that a trip to Mars and back would require thousands of pounds of food; just four crew members on a three-year mission would need more than 24,000 pounds (10,886 kilograms) of food to eat three meals per day. If those voyages could start an aeroponic garden when they landed, and synthesize other supplies (like nutrients and water) from the soil of their new home, they could extend that food supply for weeks, months, and even years without bringing the weight of extra food aboard.
A DNA PROBE PATCH TO TEST FOR FOOD CONTAMINATION Scientists at the McMaster University have now reported a a transparent, durable, and flexible sensing surface that generates a fluorescence signal in the presence of a specific target bacterium. And this new tech has the potential to replace the traditional “best before” date on food and drinks alike with a definitive indication that it’s time to chuck that roast or pour out that milk. The patch can be incorporated directly into food packaging, and signal E coli and Salmonella contamination as it happens. Dubbed “Sentinel Wrap,” the patch triggers a molecular signal that a disease-causing agent has contaminated products like meat, bottled water or milk. The triggered signal could be read by a smartphone or other devices. The patch does not affect the contents of the package. “Right now, if you want to know if there’s any contamination in a food sample, you need to bring it into a lab … and it takes at least a day or two to find out if there’s any pathogen present in that food sample,” said mechanical-biomedical engineer Tohid Didar, one of the product’s developers. “In the future, if you go to a store and you want to be sure the meat you’re buying is safe at any point before you use it, you’ll have a much more reliable way than the expiration date,” says lead author Hanie Yousefi,
a graduate student and research assistant in McMaster’s Faculty of Engineering. The signaling technology for the food test was developed in the McMaster labs of biochemist Yingfu Li. “He created the key, and we have built a lock and a door to go with it,” says Filipe, who is Chair of McMaster’s Department of Chemical Engineering. Mass producing such a patch would be fairly cheap and simple, the researchers say, as the DNA molecules that detect food pathogens can be printed onto the test material. The researchers are naming the new material “Sentinel Wrap” in tribute to the McMaster-based Sentinel Bioactive Paper Network, an interdisciplinary research network that worked on paper-based detection systems. That network’s research ultimately gave rise to the new food-testing technology. Getting the invention to market would need a commercial partner and regulatory approvals, the researchers say. They point out that the same technology could also be used in other applications, such as bandages to indicate if wounds are infected, or for wrapping surgical instruments to assure they are sterile.
By Disha Padmanabha Immune cells produce certain antibodies that attack influenza viruses from two sides. (Image: iStock/selvanegra)
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Atomically Thin Synthetic Eardrum Offers Cat-Like “Hearing” Capability Case Western Reserve University researchers are now reportedly designing a wearable device that can send and receive signals at radio frequencies even greater than those we can hear with our natural ear. Nicknamed the “drumhead”, it is 10,000,000,000,000 times smaller in volume and 100,000 times thinner than the human eardrum and can detect a much wider range of signal than other similar devices. Their work will likely contribute to making the next generation of ultralow-power communications and sensory devices smaller and with greater detection and tuning ranges. “Sensing and communication are key to a connected world,” said Philip Feng, an associate Professor of electrical engineering and computer science and corresponding author on the paper. “In recent decades, we have been connected with highly miniaturized devices and systems, and we have been pursuing ever-shrinking sizes for those devices.” The challenge with miniaturization: Also achieving a broader dynamic range of detection, for small signals, such as sound, vibration, and radio waves. “In the end, we need transducers that can handle signals without losing or compromising information at both the ‘signal ceiling’ (the highest level of an undistorted signal) and the ‘noise floor’ (the lowest detectable level),” Feng said.
Dynamic range is the ratio between the signal ceiling over the noise floor and is typically measured in decibels (dB). Human eardrums typically have a dynamic range of about 60 to 100 dB in the range of 10 Hz to 10 kHz, and human hearing rapidly drops outside this frequency range. Other animals, such as the beluga whale or common house cat can have comparable or even broader dynamic ranges in higher frequency bands. The vibrating nanoscale drumheads built by Feng and his team are composed of atomic layers of semiconductor crystals (single-, bi-, tri-, and four-layer MoS2 flakes, with a thickness of 0.7, 1.4, 2.1, and 2.8 nm), with diameters only around 1 µm. In order to duplicate this effect, the researchers needed to construct the ‘eardrums’ on an atomic level. They used a combination of nanofabrication and micromanipulation to suspend atomic layers over a silicon wafer. The team then made electrical contacts to the devices. Even for all its tiny size, the resonators show frequency “tunability,” according to the researchers, which means that tones can be manipulated by stretching the drumhead membranes through electrostatic forces. It would be similar to tuning a kettle drum in an orchestra, Feng noted. “Not only having surprisingly large dynamic range with such tiny volume and mass, they are also energy-efficient and very ‘quiet’ devices,” Feng said, “We ‘listen’ to them very carefully and ‘talk’ to them very gently.”
PANCANCER ATLAS REVEALS UTTERLY COMPLEX NATURE OF CANCER Ever since the first draft of the human genome was published, there has been an expectation that this genetic code would reveal the secrets of life, ultimately leading to novel therapeutic strategies for a multitude of diseases. To effectively identify disease genes, DNA sequencing has been frequently applied to study cohorts of individuals afflicted with the same disease so that important variants associated with disease risk can be uncovered when compared to healthy individuals. However, it remains unclear which are the key driver mutations or dependencies in a given cancer and how these influence pathogenesis and response to therapy. Although tumors of similar types and clinical outcomes can have patterns of mutations that are strikingly different, it is becoming apparent that these mutations recurrently hijack the same hallmark molecular pathways and networks. The Pan-Cancer Initiative launched as part of an international collaboration has now completed its comprehensive analysis of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. The new analysis shows that all 33 cancer types, based on their cellular and genetic makeup and independent of their anatomic site of origin, could be reclassified into 28 different molecular types, or “clusters”. Nearly two-thirds of these clusters were con-
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sidered heterogeneous as they contained up to 25 different histological tumor types that, traditionally, would all be treated differently. The PanCancer Atlas, published as a collection of 27 papers across a suite of Cell journals, sums up the work accomplished by The Cancer Genome Atlas (TCGA) – a multi-institution collaboration initiated and supported by the National Human Genome Research Institute (NHGRI) and the National Cancer Institute (NCI), both part of NIH. The program, with over $300 million in total funding, involved upwards of 150 researchers at more than two dozen institutions across North America. “Insights about how one type of cancer relates to another form of the disease can have real clinical implications,” said Josh Stuart, Baskin Professor of Biomolecular Engineering at UC Santa Cruz and an organizer of the Pan-Cancer Initiative. “In some cases, we can borrow clinical practices from better-known diseases and apply them to cancers for which treatment options are less well defined.” The PanCancer Atlas is divided into three main categories, each anchored by a summary paper that recaps the core findings for the topic. The main topics include cell of origin, oncogenic processes, and oncogenic pathways. Multiple companion papers report indepth explorations of individual topics within these categories.
By Disha Padmanabha
FIRST RAPID DIAGNOSTIC PLATFORM FOR RESPIRATORY INFECTIONS GETS FDA NOD Dutch molecular diagnostics company, Curetis, has now received the FDA approval for its multiplex assay to detect lower respiratory tract infections, as well as for the firm’s molecular diagnostic platform, Unyvero. The assay is the first multiplex lower respiratory tract infection test to be cleared by the FDA. “The launch of our Unyvero System and LRT Application Cartridge in the United States will address a pressing unmet medical need as it delivers results much faster than current standard of care microbiology culture“, said Curetis’ co-founder and Chief Operating Officer Johannes Bacher. “We expect that the LRT panel will transform our approach to the diagnosis of lower respiratory tract infections“, said Dr. Donna Mildvan, Infectious Diseases Physician and Clinical Professor of Medicine at Icahn School of Medicine at Mount Sinai, New York, NY. “Having the opportunity to characterize pneumonia by knowing the causative organism as well as relevant antibiotic resistance markers in 4 to 5 hours has great clinical implications – it is game changing and exciting.” The sample-to-answer Unyvero System together with the Unyvero LRT Application Cartridge provides rapid infectious disease testing directly from aspirate samples in un-
der five hours. It covers more than 90% of infection cases of hospitalized patients with pneumonia and provides clinicians with a comprehensive overview on genetic antibiotic resistance markers detected. Data from a clinical trial, which included more than 2,200 patient samples at nine participating U.S. hospitals, were submitted to the FDA in early 2017. Curetis’ clinical trial operations team has worked in close collaboration with the FDA’s review team to evaluate the study data set and develop relevant statistics and reports, as well as a benefit-risk analysis which was compiled with input and support from several renowned U.S. clinical experts. Curetis further plans to submit an application to the FDA for an expanded label on its diagnostic system, which would include clearance for bronchial lavage sample types and additional diagnostic targets. “We have assembled a team of high-caliber talent here at Curetis USA, and we will continue to expand our commercial organization in support of the Unyvero product launch in Q2/2018. We are truly excited to bring the innovative Unyvero Solution to clinicians, microbiologists in clinical laboratories, and above all to patients in the Unites States,” Chris Bernard, president & CEO of Curetis USA Inc. and EVP of global sales, said.
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Non-Invasive Portable Device Allows WBC Levels Estimation in Chemotherapy Patients
White-blood-cell (WBC) status is used as one indicator of immunological status in the diagnosis and treatment of multiple medical conditions, including cancer, infectious diseases, sepsis, autoimmune disorders, and in the use of immunosuppressant drugs. However, all current methods require a blood sample which involves a visit to a healthcare center and trained clinical personnel, even with finger-prick technologies. This limitation inherently restricts how frequently and quickly monitoring can be performed. MIT Bioengineers have now developed a noninvasive, portable device that could be used to monitor patients’ white blood cell levels at home, without taking blood samples. The idea is to create a device that can be used to continuously monitor immunosuppressed patients, such as those on chemotherapy, and to detect serious infections. Their tabletop prototype records video of blood cells flowing through capillaries just below the surface of the skin at the base of the fingernail. A computer algorithm can analyze the images to determine if white blood
cell levels are below the threshold that doctors consider dangerous. “Our vision is that patients will have this portable device that they can take home, and they can monitor daily how they are reacting to the treatment. If they go below the threshold, then preventive treatment can be deployed,” says Carlos Castro-Gonzalez, a postdoc in MIT’s Research Laboratory of Electronics (RLE) and the leader of the research team.
The technology does not provide a precise count of white blood cells, but reveals whether patients are above or below the threshold considered dangerous — defined as 500 neutrophils (the most common type of white blood cell) per microliter of blood. The approach proved 95 percent accurate for determining whether a patient’s white cell levels were above or below the threshold when tested with 11 subjects at different points during their chemotherapy treatment.
By Disha Padmanabha
“Based on the feature-set that our human raters identified, we are now developing an AI and machine-vision algorithm, with preliminary results that indicate the same accuracy as the raters,” says paper’s first author is Aurélien Bourquard, an RLE postdoc. The research team has applied for patents on the technology and has launched a company called Leuko. To help move the technology further toward commercialization, the researchers are building a new automated prototype. Using this new prototype, the researchers plan to test the device with addi-
tional cancer patients. They are also investigating whether they can get accurate results with shorter lengths of video. “There is a balancing act that oncologists must do,” says Sanchez-Ferro. “Normally doctors want to make chemotherapy as intensive as possible but without getting people too immunosuppressed. Current 21-day cycles are based on statistics of what most patients can take, but if you are ready early, then they can potentially bring you back early and that can translate into better survival.”
Scientists Use CRISPR Gene Editing System to Perform Parallel Edits The first use of CRISPR to edit human cells in a dish was reported in 2013. It’s since been touted as an easy way to alter people’s DNA, promising to banish what are currently lethal or lifelong maladies with a single treatment that fixes them at the genetic root. And in a piece Bill Gates wrote for the Foreign Affairs this week, he put further emphasis on how unique this technology is and how our researches should be taken up a notch higher to meet growing demand for food and to improve disease prevention, particularly for malaria. “It would be a tragedy to pass up the opportunity,” he writes. Now, in another exciting advance, researchers at the University of California have successfully tested speeding up this process of gene editing. In terms of understanding the functional effects of DNA sequence variants, one promising avenue is precise editing with the CRISPR–Cas9 system. Recent studies have used CRISPR libraries to generate many frameshift mutations genome wide through faulty repair of CRISPR-directed breaks by nonhomologous end joining (NHEJ).
However, it is a tedious process- painstakingly introducing a variant, monitoring the effect gene by gene. Researchers currently analyze each edit one at a time, a process that can take weeks. The UCLA team has now tweaked the CRISPR tech so as to allow researchers to monitor the outcome of tens of thousands of gene edits in the time it currently takes to analyze a few. The UCLA investigators invented a method that physically connected thousands of guides to their partner patches, allowing a perfectly matched set to be delivered to each cell. In their study, the team physically connected thousands of guides to their partner patches, forming a perfectly matched set for each cell. In a test of a class of genetic mutations suspected to be harmful to cells, they used yeast because cellular changes in response to gene alterations happen quickly and are easy to observe. Researchers grew millions of cells inside a flask of fluid. CRISPR delivered a customized set of paired guides and patches to each cell- about 10,000 distinct mutations simultaneously. The guide and patches instructed CRISPR where to snip the gene and what edit to introduce. This process distinguished cells
By Disha Padmanabha
that died or survived after four days.
damaging genetic edits from the harmless.
“We were surprised to find that some genes believed to be essential for cell function actually aren’t,” said first author Meru Sadhu, a postdoctoral researcher in Kruglyak’s lab. “In other genes, only a part of the protein is essential, while the rest can be chopped off and the cell will still survive.”
“We can now edit the genome in thousands of different ways, while observing positive or negative effects on cells,” said said lead author Leonid Kruglyak, chair of human genetics at the David Geffen School of Medicine at UCLA. “Our ultimate goal is to help scientists zero in on the genetic culprit for a disease, leading doctors to a firm diagnosis and allowing patients to obtain the most effective treatment.“
The UCLA team hopes their technique will help scientists to rapidly distinguish the most
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Biomarkers Could Help Predict Recurrence of Malignant Brain Tumor Glioblastoma (GBM) is a highly aggressive brain cancer and accounts for 46.6% of primary malignant brain tumors with a 5-year overall survival estimate post-diagnosis of 5.5%. The WHO histomorphology and grading classification of diffuse gliomas does not have predictive clinical outcomes after GBMs have developed. Treating initially lower-grade glioma (LGG) that relapses and undergoes malignant transformation to GBM is one of the greatest challenges in neuro-oncology. To date, despite the efforts of the neuro-oncology community, no treatment regimens or bona fide biomarkers that significantly translate into a survival benefit to GBM patients have been identified. Now, scientists led by the Henry Ford Health System’s Department of Neurosurgery and Department of Public Health Sciences in Michigan, found that 9.5 percent had a distinct epigenetic alteration at genomic sites that are active in regulating genes associated with aggressive tumors that include glioblastoma. The group carried out an evaluation of 200 brain tumor samples from 77 patients with diffuse glioma harboring IDH mutation, the most important assortment of main and re-
current gliomas from the identical sufferers to date. Comparing samples from the sufferers’ preliminary analysis with these from their illness recurrence, researchers targeted, particularly, on a definite epigenetic modification occurring alongside the DNA phase, a course of referred to as DNA methylation. Previously, their analysis confirmed that when there was no change within the DNA methylation, sufferers had an excellent medical consequence. When the DNA methylation was misplaced, sufferers had a poor end result. In this newest research, the authors have been in a position to determine a set of epigenetic biomarkers that may predict, at a affected person’s preliminary analysis, which tumors are probably to recur with a extra aggressive tumor sort. Houtan Noushmehr, Ph.D., Henry Ford Department of Neurosurgery, Hermelin Brain Tumor Center, and senior author of the study, says this discovery could make a huge difference when a patient is first diagnosed. “To date, we really don’t have any predictive clinical outcomes once a patient is diagnosed with glioma. By pinpointing these
Cardiovascular Risk Incidence Predicting Blood Test Developed Circulating branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) are strong predictors of type 2 diabetes mellitus (T2D), but their association with cardiovascular disease (CVD) is uncertain. Now, in a new study, researchers of the Brigham and Women’s Hospital hypothesized that plasma BCAAs are positively associated with CVD risk and evaluated whether this was dependent on an intermediate diagnosis of T2D. “We examined more than 27,000 women in the Women’s Health Study and found that a one-time measurement of branched chain amino acids in the blood stream – a test that now can be easily done – predicted future risk of cardiovascular events to the same extent and independent of LDL cholesterol and other risk factors,” said corresponding author Samia Mora, MD, of the Center for Lipid Metabolomics at BWH. “This was particularly so for women who developed type 2 diabetes prior to their cardiovascular disease.” In the course of their investigation, the team of researchers measured BCAA levels in blood samples using NMR spectrometry. Of
the more than 27,000 women studied, 2,207 experienced a cardiovascular event over the 18 year follow up period. They noticed an association between BCAA levels and incident of CVD events. This association was much more pronounced in women who developed diabetes before experiencing a cardiovascular event. The researchers then adjusted for other biomarkers related to diabetes – including hbA1c – finding evidence that BCAAs may be tied to downstream biomarkers of type 2 diabetes metabolism. “Impaired BCAA metabolism may represent a shared pathway of the metabolic pathophysiology that links the risks of T2D and CVD,” the authors conclude. “There is little known at this time as to what leads to elevated levels of BCAAs or what can be done clinically to reduce them, and if this leads to a reduction in risk, but further research will target these important questions,” said Tobias.
By Disha Padmanabha
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By Disha Padmanabha
molecular abnormalities, we can begin to predict how aggressive a patient’s recurrence will be and that can better inform the treatment path we recommend from the very beginning.” Of the 200 tissue samples, 10% were found to have a distinct epigenetic alteration at genomic sites known to be functionally active in regulating genes that are known to be associated with aggressive tumors such as glioblastoma. “This research presents a set of testable
DNA-methylation biomarkers that may help clinicians predict if someone’s brain tumor is heading in a more or less aggressive direction, essentially illustrating the behavior of a patient’s disease,” says James Snyder, D.O., study co-author and neuro-oncologist, Henry Ford Department of Neurosurgery and Hermelin Brain Tumor Center. “If we can identify which brain tumors will have a more aggressive course at the point of initial diagnosis then hopefully we can change the disease trajectory and improve care for our patients.”
STUDY DISPUTES NEUROGENESIS, FINDS ADULT BRAIN PRODUCING NEW CELLS Columbia University researchers have now identified thousands of immature neurons in the brain region, countering the popular notion of stagnant brain growth as we age. There’s been considerable debate about whether the human brain has the capacity to make new neurons into adulthood. This recently published study offers some compelling new evidence that’s the case. These findings suggest that a healthy person in his or her seventies may have about as many young neurons in a portion of the brain essential for learning and memory as a teenager does. To come to this conclusion, lead author Dr. Maura Boldrini, a research scientist at Columbia University’s department of psychiatry, and her colleagues looked at the brains of 28 deceased people aged 14 to 79. Their goal was to see whether aging affects neuron production. Previous research had shown that neurogenesis slows down in aging mice and nonhuman primates. Boldrini’s group wanted to see whether a similar pattern occurred in humans. “The exciting part is that the neurons are there throughout a lifetime,” said Dr Maura Boldrini. “It seems that indeed humans are different from mice – where [neuron production] goes down with age really fast – and this could mean that we need these neurons for our complex learning abilities and cognitive behavioural responses to emotions.” The brain’s hippocampus, which is responsible for memory and learning, has been a major focus of studies on neurogenesis and stem cell biology. Although neuroimaging studies of humans show that continued
growth in this structure occurs in adulthood, many scientists have argued that this represents existing neurons growing larger, or an expansion of blood vessels or other internal support structures, rather than the addition of new neurons. For their analysis, the research team spent 5 years collecting brain tissue from 59 people who had died or had such tissue removed during surgery for epilepsy at different ages, ranging from before birth to 77 years of age. They used fluorescent antibodies to label proteins specific to cells at different states of maturity. With an electron microscope, they also looked for the characteristic long, slender, simple shapes of young neurons. They found that people have large numbers of neural stem cells and progenitors early in life—an average of 1618 young neurons per square millimeter of brain tissue at birth. But these cells did not go on to form a proliferating layer of neural stem cells, and production of new neurons dropped 23-fold between 1 and 7 years of age, the team reports. By adulthood the supply of young neurons had petered out entirely. “It is possible that ongoing hippocampal neurogenesis sustains human-specific cognitive function throughout life and that declines may be linked to compromised cognitive-emotional resilience,” said Boldrini, who hopes her research will contribute to further investigation of age-related conditions such as Alzheimer’s.
By Disha Padmanabha
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New Framework for Future Alzheimer’s Research Proposed Owing to a 15-year record of clinical failures and pulled by an FDA searching for a practical new path forward for Alzheimer’s drug research, a joint committee organized by the NIH’s National Institute of Aging and the Alzheimer’s Association is suggesting a biomarker-based approach to defining the illness that can guide new development efforts. This proposed “biological construct” is based on measurable changes in the brain and is expected to facilitate better understanding of the disease process and the sequence of events that lead to cognitive impairment and dementia. The identification of Alzheimer’s disease (AD) biomarkers and their ability to measure pathology antemortem has led to a fundamental reconsideration of the pathogenesis of AD. The importance of biomarkers was already reflected in revised diagnostic criteria proposed by the National Institute on Aging and the Alzheimer’s Association in 2011. Beginning in 2016, the NIA and AA convened a new workgroup to develop a research framework for AD that embodied the paradigm shift occurring in the field. Rather than conceptualizing AD primarily as a clinicopathological entity, biomarkers have demonstrated that AD pathology exists over
the continuum of the disease–from a stage preceding overt symptomatology (the “preclinical state”) to the progressively more impaired symptomatic states of mild cognitive impairment (MCI) and dementia. The same biomarkers have also shown in greater resolution how dementia may occur in people with both AD and non-AD pathology. With this construct, researchers can study Alzheimer’s, from its earliest biological underpinnings to outward signs of memory loss and other clinical symptoms, which could result in a more precise and faster approach to testing drug and other interventions. “With the aging of the global population, and the ever-escalating cost of care for people with dementia, new methods are desperately needed to improve the process of therapy development and increase the likelihood of success,” said Maria Carrillo, Ph.D., Alzheimer’s Association chief science officer and a co-author of the new article. “This new Research Framework is an enormous step in the right direction for Alzheimer’s research.” According to the authors, “This evolution of the previous diagnostic criteria is in line with most chronic diseases that are defined
By Disha Padmanabha
biologically, with clinical symptoms being a … consequence.” They say, “the goal of much of medicine is to identify and treat diseases prior to overt symptoms. The [NIA-AA Research] Framework is intended to provide a path forward to … prevention trials of Alzheimer’s disease among persons who are clinically asymptomatic.” The biomarker-based definition relies on three neuropathological measures of beta-amyloid deposition, abnormal microtubule-associated protein tau (tau; MAPT; FTDP-17) and neurodegeneration, collectively called the “ATN system” that can be measured with imaging technology and analysis of cerebral fluid samples. The authors suggest the ATN framework can help in the design and execution of observational studies and clinical trials, and can enable trials to use biologically defined target populations in addition to clinically defined
populations. Innovative trial approaches that have been tested in other disease areas such as oncology- platform trials, umbrella and basket designs- could be used with stratification of patients by ATN profiling. In an accompanying editorial, members of the NIH who worked on the report emphasized that the framework is still a work in progress. As science advances, even more biomarkers might need to be considered, they admit. And though the NIH expects and hopes scientists use the framework in designing their studies when submitting for grants, they won’t shut out those who don’t use these specific biomarkers in their research. “The NIH will consider research applications using the Framework as well as proposals using alternative schemes when designing experimental approaches,” they wrote. “The NIH continues to welcome applications where biomarkers may not be appropriate.”
See No More of those Pricks! Non-Invasive Glucose Monitoring Patch is Here
Finally, an end to all the pricking and pestering. It is estimated that around 30.3 million people in the United States are living with diabetes, and there are around 1.5 million new cases diagnosed every year. And currently, there is no available needle-free approach for diabetics to monitor glucose levels in the interstitial fluid. Now however, scientists at the Bath University have designed an electronic patch that non-invasively measure glucose levels through the skin. It works by drawing out glucose from fluid between cells across hair follicles, which are individually accessed via an array of miniature sensors using a small electric current. The glucose collects in tiny reservoirs and is measured. An important advantage of this device over others is that each miniature sensor of the array can operate on a small area over an individual hair follicle – this significantly reduc-
es inter- and intra-skin variability in glucose extraction and increases the accuracy of the measurements taken such that calibration via a blood sample is not required. Further, the test can be taken as often as once every 10 to 15 minutes over a period of several hours. It is hoped that once commercialized, the inexpensive disposable device could wirelessly transmit those readings to an app on the user’s smartphone, providing alerts when necessary.
“The monitor developed at Bath promises a truly calibration-free approach, an essential contribution in the fight to combat the ever-increasing global incidence of diabetes,” he continued.
“A non-invasive – that is, needle-less – method to monitor blood sugar has proven a difficult goal to attain,” said professor of the university’s department of pharmacy and pharmacology Richard Guy. “The closest that has been achieved has required either at least a single-point calibration with a classic ‘finger-stick’, or the implantation of a pre-calibrated sensor via a single needle insertion.”
“The specific architecture of our array permits calibration-free operation, and it has the further benefit of allowing realization with a variety of materials in combination,” said Dr. Adelina Ilie, from the University’s Department of Physics. “We utilized graphene as one of the components as it brings important advantages: specifically, it is strong, conductive, flexible, and potentially low-cost and environmentally friendly. In addition, our de-
By Disha Padmanabha
sign can be implemented using high-throughput fabrication techniques like screen printing, which we hope will ultimately support a disposable, widely affordable device.” In lab tests, the patch has been successfully used to monitor fluctuating blood glucose levels both in healthy human volunteers, and on pig skin with glucose levels representing the range seen in human diabetics. The scientists are now planning on optimizing the number of sensors in the patch, demonstrating its functionality over a 24-hour wear period, and performing clinical trials.
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April 17th, 2018.
STAYING FIT COULD HELP STEER CLEAR OF GENETIC HEART DISEASES
By Disha Padmanabha
It takes a special person to enjoy every single workout every single time. You’re only human, right? So getting frustrated, angry, sleepy, teary, competitive and exhausted is all part of the process. That said, so is feeling happy, accomplished and proud when you make it to the end of your workout. And if you’re the kind that hates exercising with the fiery passion of a thousand suns, this piece.. erm, well I hope gets you right on back track (no pun intended). A new study indicates exercise may be the best way to keep off heart disease- even for those with a genetic pre-disposition.
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“The main message of this study is that genetic risk isn’t deterministic,” says Erik Ingelsson, M.D., Ph.D., professor of medicine at Stanford University School of Medicine and lead author of the study published in the American Heart Association journal, Circulation. “Even if your parents died early of heart disease, you can reduce your risk to the level of someone with no family history of the disease by increasing your fitness.” “This study further buoys what I’ve always said—that exercise is good for everyone and everything,” says Consumer Reports’ chief medical advisor Marvin M. Lipman, M.D.
In one of the largest observational studies on fitness and heart disease, researchers examined data collected from nearly a half-million people in the UK Biobank database. The investigators found that people with higher levels of grip strength, physical activity, and cardiorespiratory fitness had reduced risks of heart attacks and stroke, even if they had a genetic predisposition for heart disease. For participants deemed at intermediate genetic risk for cardiovascular diseases, those with the strongest grips were 36 percent less likely to develop coronary heart disease and had a 46 percent reduction in their risk for atrial fibrillation compared with study partic-
ipants who had the same genetic risk and the weakest grips. Researchers determined various levels of genetic risk according to measurements based on discoveries from genomewide association studies, the most common study design to discover genetic variation associated with disease. The study authors explained that the results of this research could have important implications for public health, especially considering the fact that little is known about the effects of exercise in individuals who have genetically inherited a risk of cardiovascular disease.