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Updates found with 'treat congenital disease'

A tool that tracks and stops bacterial blight outbreaks in ricericetoday.irri.org/a-tool-that-tracks-and-stops-bacterial-blight-outbreaks-in-rice/A new, faster, and more accurate way of identifying infectious organisms—down to their genetic fingerprint—could finally put farmers a step ahead of bacterial blight. Severe bacterial blight infection in a susceptible rice variety from West Java, Indonesia. (Photo by R. Oliva)Severe bacterial blight infection in a susceptible rice variety from West Java, Indonesia. (Photo by R. Oliva)A revolutionary tool called the PathoTracer has been developed at the International Rice Research Institute (IRRI) and it can identify the exact strain of the bacterium that causes bacterial blight present in a field in a matter of days instead of several months of laboratory work.“It’s like a paternity test that uses DNA profiling, ” said Ricardo Oliva, a plant pathologist at IRRI. “It will not only tell you that you have bacterial blight in your plant. It will tell you the particular strain of the pathogen so that we can recommend varieties resistant to it.”For more than four years, Dr. Oliva and his team worked on deciphering the genetic code of Xanthomonas oryzae pv. oryzae, the pathogen that causes bacterial blight, to develop the test. Bacterial blight is one of the most serious diseases of rice. The earlier the disease occurs, the higher the yield loss—which could be as much as 70% in vulnerable varieties.“Bacterial blight is a persistent disease in rice fields, ” said Dr. Oliva. “The epidemic builds up every season when susceptible varieties are planted. The problem is that the bacterial strains vary from one place to another and farmers don’t know which are the resistant varieties for that region. We were always behind because the pathogens always moved and evolved faster.”Identifying the strains of bacterial blight present in the field requires a lot of labor and time. You need people to collect as many samples as they can over large areas to accurately monitor the pathogen population. In addition, isolating the pathogens in the lab is laborious and it typically takes several months or even a year to determine the prevalent strains in a region.The PathoTracer can identify the local bacteria in the field using small leaf discs as samples. The samples will be sent to a certified laboratory to perform the genetic test and the results will be analyzed by IRRI.The team that developed PathoTracer. Left row: Maritess Carillaga, Cipto Nugroho, Ian Lorenzo Quibod, and Genelou Grande. Right row: Veronica Roman-Reyna, Sapphire Thea Charlene Coronejo, and Dr. Oliva. Not in photo: Eula Gems Oreiro, EiEi Aung, and Marian Hanna Nguyen. (Photo by Isagani Serrano, IRRI)The team that developed PathoTracer. Left row (front to back): Maritess Carillaga, Cipto Nugroho, Ian Lorenzo Quibod, and Genelou Grande. Right row: Veronica Roman-Reyna, Sapphire Thea Charlene Coronejo, and Dr. Oliva. Not in photo: Eula Gems Oreiro, EiEi Aung, Epifania Garcia, Ismael Mamiit, and Marian Hanna Nguyen. (Photo by Isagani Serrano, IRRI)“It takes only a few days to analyze the samples, ” Dr. Oliva explained. “With the PathoTracer, we can bring a year’s work down to probably two weeks. Because the tool can rapidly and efficiently monitor the pathogen present in each season, the information can be available before the cropping season ends.”It’s like knowing the future, and predicting what would happen the next season can empower the farmers, according to Dr. Oliva.“Recognizing the specific local bacteria present in the current season can help us plan for the next, ” he added. “We can come up with a list of recommended rice varieties that are resistant to the prevalent pathogen strains in the locality. By planting the recommended varieties, farmers can reduce the risk of an epidemic in the next season and increase their profits.”The PathoTracer was pilot tested in Mindanao in the southern part of the Philippines in April 2017. The rains came early in the region, just after the peak of the dry season, and that triggered an outbreak of bacterial blight.“We went there and took samples from different fields, ” Dr. Oliva said. “By the end of April, we had the results and we were able to come up with a list of resistant varieties that could stop the pathogen. We submitted our recommendation to give farmers a choice in reducing the risk. If the farmers planted the same rice varieties in the succeeding rainy seasons, I am 100% sure the results would be very bad.”The PathoTracer can run thousands of samples and can, therefore, easily cover large areas, making it an essential tool for extension workers of agriculture departments and private-sector rice producers, or it can be incorporated into monitoring platforms such as the Philippine Rice Information System (PRiSM) or Pest and Disease Risk Identification and Management (PRIME) to support national or regional crop health decision-making.“National breeding programs could also make more informed decisions, ” Dr. Oliva said. “If you know the pathogen population in the entire Philippines, for example, the country’s breeding program could target those strains.”IRRI is interested in expanding the genetic testing tool to include rice blast and, further down the road, all bacteria, viruses, and fungi that infect rice.The speed at which PathoTracer can identify the strains of bacterial blight present in the field can be used for recommending resistant rice varieties to farmers for planting in the next cropping season. (Photo: IRRI)The speed at which PathoTracer can identify the strains of bacterial blight present in the field can be used for recommending resistant rice varieties to farmers for planting in the next cropping season. (Photo: IRRI)The PathoTracer has been tested in other Asian countries and IRRI expects to roll it out early in 2018. When it becomes available, the expected potential impact of the PathoTracer on a devastating disease that affects rice fields worldwide would be huge.“Imagine if this tool prevented bacterial blight outbreaks every season across Asia, ” said Dr. Oliva. “It’s super cool!”For more information about bacterial blight, see Section II, Chapter 2 of IRRI’s Rice Diseases Online Resource
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A new Harvard Medical School GuideReady to put a stop to the itching, burning, and discomfort of hemorrhoids?This information-packed guide reveals how you can prevent and treat hemorrhoids.Healing Hemorrhoids In Healing Hemorrhoids, you'll discover:✓ Everything you need to know about the types, causes, and symptoms of hemorrhoids✓ Symptoms that might be signs of other, more serious conditions✓ How to prevent constipation—the #1 cause of hemorrhoids✓ The differences between stool softeners, suppositories, and laxatives✓ Non-surgical, office-based hemorrhoid treatments as well as surgical procedures✓ 19 high-fiber foods that can help keep you regularRead MoreIt's the healthcare issue no one likes talking about: hemorrhoids. Yet more than 75% of people over age 45 experience hemorrhoids. If you have hemorrhoids, you know just how uncomfortable they can be. Now, with Healing Hemorrhoids, a new guide from the experts at Harvard Medical School, you'll learn how to take charge of your hemorrhoids and get back to enjoying life.Everything about hemorrhoids you were too embarrassed to askHealing Hemorrhoids gives you a complete understanding of hemorrhoids (in the comfort and privacy of your own home!). For example, you'll read about the two types of hemorrhoids—internal and external—and their causes and symptoms. (Here's some good news: hemorrhoids are not dangerous and serious complications are rare.) The guide also reveals who is more likely to get hemorrhoids, and explains how hemorrhoids are diagnosed.The #1 tip for preventing hemorrhoidsWhat's the key to preventing hemorrhoids? Preventing constipation! The guide explains in detail how constipation occurs, and what you can do to avoid it. For example, you'll learn how adding fiber to your diet, drinking plenty of water, and exercising can make a big difference in your bowel health. You also get an in-depth look at stool softeners, laxatives, prescription medicines, and other means of reducing constipation.Simple lifestyle changes that help you fight hemorrhoidsThe guide offers additional easy-to-try tips for preventing and relieving hemorrhoids. These include elevating your feet when using the toilet, sitting on soft cushions vs. hard surfaces, and "training" your bowels to stay regular.A complete overview of your treatment optionsWhen it comes to treating hemorrhoids, you have many options, depending on your particular hemorrhoid condition. Healing Hemorrhoids includes safe and easy self-help remedies such as sitz baths, fiber supplements, and topical treatments like Tucks and Preparation H. The guide also goes over non-surgical, office-based treatments for hemorrhoids, as well as surgical procedures (and what to expect after surgery, too).Don't let hemorrhoids slow you down. Get your copy of Healing Hemorrhoids today!Read MoreTo your good health, Howard E. LeWine, M.D.Chief Medical Editor, Harvard Health Publishing
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IGIB researchers partially reverse a rare disorderThe HinduR. Prasad10 FEBRUARY 2018 18:13 ISTUPDATED: 10 FEBRUARY 2018 18:14 IST The syndrome also affects about one in one lakh people, causing a range of defectResearchers at Delhi’s Institute of Genomics & Integrative Biology (CSIR-IGIB) have for the first time used zebra fish to model the rare genetic disorder — Rubinstein Taybi Syndrome (RSTS) — seen in humans. They have also used two small molecules to partially reverse some of the defects caused by the disorder in zebrafish, thus showing them to be an ideal animal model for screening drug candidates. There is currently no cure or treatment for the disorder.The Rubinstein Taybi Syndrome has a frequency of about one in one lakh people, and causes intellectual disability, growth retardation (short stature), craniofacial deformities, heart defects and broad thumbs and toes. The results were published in the journal Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.Close to human genomeSince zebrafish genome has very close similarity to human genome and the embryonic developmental is very similar in the two, the team led by Dr. Chetana Sachidanandan at IGIB went about checking if EP300, one of the two genes that cause the disorder is present in the fish and if mutations in this gene result in a RSTS-like disease in fish.Using chemicals, the researchers inhibited the activity of the protein Ep300 to see if this resulted in the manifestation of the disorder in the brain, heart, face and pectoral fins (equivalent to forearm in humans). “Like in the case of humans, the same organs were affected in the fish when the functioning of the protein was stopped. This helped in confirming that the protein in question does the same functions in fish and humans, ” she says.Since zebrafish commonly has two copies of many human genes, the researchers first checked if one or both the genes were functional and equivalent to the human gene that causes the disorder. “We found Ep300a gene was active and functional while Ep300b was not, ” says Prof. Tapas K. Kundu from the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bengaluru, the other corresponding author. The Ep300a gene is responsible for producing a protein (Ep300) that opens up the DNA.“The protein Ep300 is evolutionarily conserved from fish to humans. Though the Ep300 gene has been earlier identified in fish, its function was not known, ” says Prof. Kundu.Reversal of effectsLike in the case of fish treated with chemicals manifesting the disorder, fish mutants that lacked the Ep300a gene too exhibited defects very similar to those seen in humans.“When we introduced excess amount of a tiny portion of the Ep300a protein in the mutants, the craniofacial deformities became less severe [mutants had severed craniofacial deformities] and pectoral fins in the fish became normal, ” she says.But neuronal defects were not reversed, even partially. “It might be because only a portion of the protein was put into the fish. Probably, that potion isn’t sufficient to compensate for the loss of the whole protein, ” she explains.“It’s proof-of-concept that just a piece of the protein is sufficient to reverse some defects, even if only partially, in zebrafish, ” Dr. Sachidanandan says.Alternatively, the researchers used two small molecules to reverse the defects. If the protein Ep300 is responsible for opening the DNA, there are other proteins that are responsible for closing the DNA.The two molecules were found from a screen of compounds well known for their ability to inhibit proteins responsible for closing the DNA.Like in the case when excess amount of Ep300 protein was introduced, both the molecules could partially restore facial defects but not the neuronal defects.“Introducing excess amount of a portion of the ep300 protein showed greater rescue of deformities than the small molecules, ” says Aswini Babu from IGIB and first author of the paper. “But rescuing the deformities using small molecules is a relatively easier and better option.”
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A Resurgence in Natural Product-Based Drug DiscoveryAdvances in analytical technology are making the screening of natural products and their substructures more viable.Jan 24, 2018By Simon PearcePharmaceutical Technology's In the Lab eNewsletterVolume 13, Issue 2Natural products and their substructures have long been valuable starting points for medicinal chemistry and drug discovery. Since the earliest days of medicine, we’ve turned to nature for our treatments. From the application of digitalis extract as a remedy for heart failure, to the use of Vitamin C to prevent scurvy, many of the first drug treatments were developed by studying the medicinal effects of plants, and isolating the specific compounds responsible for their therapeutic properties. As the knowledge of medicinal chemistry and chemical synthesis advances, the pharmaceutical industry has become more adept at creating synthetic analogues of natural products to reduce the reliance on natural sources, or to improve drug properties such as therapeutic potency, bioavailability, or metabolism by carefully modifying a molecule’s structure (1). Indeed, it’s thought that approximately 40% of drugs available on the market today are derived from chemical structures found in nature (2, 3). Yet over the past few decades, the influence of natural products on drug discovery has notably reduced, in part due to the perceived difficulties of isolating and synthesizing these complex molecules, as well as the challenges associated with screening them using high throughput assays, which are commonly used to identify potential lead compounds.The industry, however, could be at a turning point. In recent years, there has been a resurgence of interest in the inclusion of natural products and their substructures in compound screening collections. Here, the author considers how advances in technology and adoption of alternative screening strategies are playing a role in revitalizing natural product-based drug discovery.While nature has been an important source of medicines throughout human history, the value of natural products in drug discovery has been somewhat overlooked in recent times. There is, however, a resurgence of interest in their use, driven to a large extent by the recognition of their enormous potential in the search for new antimicrobials and their efficacy to challenging targets based on the disruption of protein–protein interactions. Alternative screening strategies, such as fragment-based and phenotypic approaches, as well as advances in assay detection technology, have the potential to open up unexplored areas of chemical space populated by these important structures in the search for new and effective treatments.
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In the future we won’t edit genomes—we’ll just print out new onesWhy redesigning the humble yeast could kick off the next industrial revolution.by Bryan Walsh February 16, 2018At least since thirsty Sumerians began brewing beer thousands of years ago, Homo sapiens has had a tight relationship with Saccharomyces cerevisiae, the unicellular fungus better known as brewer’s yeast. Through fermentation, humans were able to harness a microscopic species for our own ends. These days yeast cells produce ethanol and insulin and are the workhorse of science labs.That doesn’t mean S. cerevisiae can’t be further improved—at least not if Jef Boeke has his way. The director of the Institute for Systems Genetics at New York University’s Langone Health, Boeke is leading an international team of hundreds dedicated to synthesizing the 12.5 million genetic letters that make up a yeast’s cells genome.In practice, that means gradually replacing each yeast chromosome—there are 16 of them—with DNA fabricated on stove-size chemical synthesizers. As they go, Boeke and collaborators at nearly a dozen institutions are streamlining the yeast genome and putting in back doors to let researchers shuffle its genes at will. In the end, the synthetic yeast—called Sc2.0—will be fully customizable.“Over the next 10 years synthetic biology is going to be producing all kinds of compounds and materials with microorganisms, ” says Boeke. “We hope that our yeast is going to play a big role in that.”Think of the project as something like Henry Ford’s first automobile—hand built and, for now, one of a kind. One day, though, we may routinely design genomes on computer screens. Instead of engineering or even editing the DNA of an organism, it could become easier to just print out a fresh copy. Imagine designer algae that make fuel; disease-proof organs; even extinct species resurrected.Jef Boeke leads an effort to create yeast with a man-made genome.“I think this could be bigger than the space revolution or the computer revolution, ” says George Church, a genome scientist at Harvard Medical School.Researchers have previously synthesized the genetic instructions that operate viruses and bacteria. But yeast cells are eukaryotic—meaning they confine their genomes in a nucleus and bundle them in chromosomes, just as humans do. Their genomes are also much bigger.That’s a problem because synthesizing DNA is still nowhere near as cheap as reading it. A human genome can now be sequenced for $1, 000, with the cost still falling. By comparison, to replace every DNA letter in yeast, Boeke will have to buy $1.25 million worth of it. Add labor and computer power, and the total cost of the project, already under way for a decade, is considerably more.Along with Church, among others, Boeke is a leader of GP-write, an organization advocating for international research to reduce the cost of designing, engineering, and testing genomes by a factor of a thousand over the next decade. “We have all kinds of challenges facing ourselves as a species on this planet, and biology could have a huge impact on them, ” he says. “But only if we can drive down costs.”Bottom upA scientist named Ronald Davis at Stanford first suggested the possibility of synthesizing the yeast genome at a conference in 2004—though initially, Boeke didn’t see the point. “Why would anyone want to do this?” he recalls thinking.But Boeke came around to the idea that manufacturing a yeast genome might be the best way to comprehend the organism. By replacing each part, you might learn which genes are necessary and which the organism can live without. Some team members call the idea “build to understand.”“It’s a different take on trying to understand how living things work, ” says Leslie Mitchell, a postdoctoral fellow in the NYU lab and one of the main designers of the synthetic yeast. “We learn what gaps in our knowledge exist in a bottom-up genetic approach.”Joel Bader, a computer scientist at Johns Hopkins, signed on to develop software that let scientists see the yeast chromosomes on a screen and keep track of versions as they changed, like a Google Docs for biology. And in 2008, to make the DNA, Boeke launched an undergraduate course at Hopkins called “Build a Genome.” Students would learn basic molecular biology as each one assembled a continuous stretch of 10, 000 DNA letters that would go toward the synthetic-yeast project. Later, several institutions in China joined to share the workload, along with collaborators in Britain, Australia, and Japan.“We assign chromosomes to individual teams, like assigning a chapter of a book, and they have the freedom to decide how to do it, as long as it’s based 100 percent on what we design, ” says Patrick Cai, a synthetic biologist at the University of Manchester and the yeast project’s international coordinator.Next stepsIt took Boeke and his team eight years before they were able to publish their first fully artificial yeast chromosome. The project has since accelerated. Last March, the next five synthetic yeast chromosomes were described in a suite of papers in Science, and Boeke says that all 16 chromosomes are now at least 80 percent done. These efforts represent the largest amount of genetic material ever synthesized and then joined together.It helps that the yeast genome has proved remarkably resilient to the team’s visions and revisions. “Probably the biggest headline here is that you can torture the genome in a multitude of different ways, and the yeast just laughs, ” says Boeke.
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New DNA nanorobots successfully target and kill off cancerous tumorsBY SARAH BUHRFeb 12, 2018Science fiction no more — in an article out today in Nature Biotechnology, scientists were able to show tiny autonomous bots have the potential to function as intelligent delivery vehicles to cure cancer in mice.These DNA nanorobots do so by seeking out and injecting cancerous tumors with drugs that can cut off their blood supply, shriveling them up and killing them.“Using tumor-bearing mouse models, we demonstrate that intravenously injected DNA nanorobots deliver thrombin specifically to tumor-associated blood vessels and induce intravascular thrombosis, resulting in tumor necrosis and inhibition of tumor growth, ” the paper explains.DNA nanorobots are a somewhat new concept for drug delivery. They work by getting programmed DNA to fold into itself like origami and then deploying it like a tiny machine, ready for action.DNA nanorobots, Nature Biotechnology 2018The scientists behind this study tested the delivery bots by injecting them into mice with human breast cancer tumors. Within 48 hours, the bots had successfully grabbed onto vascular cells at the tumor sites, causing blood clots in the tumor’s vessels and cutting off their blood supply, leading to their death.Remarkably, the bots did not cause clotting in other parts of the body, just the cancerous cells they’d been programmed to target, according to the paper.The scientists were also able to demonstrate the bots did not cause clotting in the healthy tissues of Bama miniature pigs, calming fears over what might happen in larger animals.The goal, say the scientists behind the paper, is to eventually prove these bots can do the same thing in humans. Of course, more work will need to be done before human trials begin.Regardless, this is a huge breakthrough in cancer research. The current methods of either using chemotherapy to destroy every cell just to get at the cancer cell are barbaric in comparison. Using targeted drugs is also not as exact as simply cutting off blood supply and killing the cancer on the spot. Should this new technique gain approval for use on humans in the near future it could have impressive affects on those afflicted with the disease
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