News Article | April 18, 2017
MIT researchers have developed a way to make extremely high-resolution images of tissue samples, at a fraction of the cost of other techniques that offer similar resolution. The new technique relies on expanding tissue before imaging it with a conventional light microscope. Two years ago, the MIT team showed that it was possible to expand tissue volumes 100-fold, resulting in an image resolution of about 60 nanometers. Now, the researchers have shown that expanding the tissue a second time before imaging can boost the resolution to about 25 nanometers. This level of resolution allows scientists to see, for example, the proteins that cluster together in complex patterns at brain synapses, helping neurons to communicate with each other. It could also help researchers to map neural circuits, says Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT. “We want to be able to trace the wiring of complete brain circuits,” said Boyden, the study’s senior author. “If you could reconstruct a complete brain circuit, maybe you could make a computational model of how it generates complex phenomena like decisions and emotions. Since you can map out the biomolecules that generate electrical pulses within cells and that exchange chemicals between cells, you could potentially model the dynamics of the brain.” This approach could also be used to image other phenomena such as the interactions between cancer cells and immune cells, to detect pathogens without expensive equipment, and to map the cell types of the body. Former MIT postdoc Jae-Byum Chang is the first author of the paper, which appears in the April 17 issue of Nature Methods. To expand tissue samples, the researchers embed them in a dense, evenly generated gel made of polyacrylate, a very absorbent material that’s also used in diapers. Before the gel is formed, the researchers label the cell proteins they want to image, using antibodies that bind to specific targets. These antibodies bear “barcodes” made of DNA, which in turn are attached to cross-linking molecules that bind to the polymers that make up the expandable gel. The researchers then break down the proteins that normally hold the tissue together, allowing the DNA barcodes to expand away from each other as the gel swells. These enlarged samples can then be labeled with fluorescent probes that bind the DNA barcodes, and imaged with commercially available confocal microscopes, whose resolution is usually limited to hundreds of nanometers. Using that approach, the researchers were previously able to achieve a resolution of about 60 nanometers. However, “individual biomolecules are much smaller than that, say 5 nanometers or even smaller,” Boyden said. “The original versions of expansion microscopy were useful for many scientific questions but couldn’t equal the performance of the highest-resolution imaging methods such as electron microscopy.” In their original expansion microscopy study, the researchers found that they could expand the tissue more than 100-fold in volume by reducing the number of cross-linking molecules that hold the polymer in an orderly pattern. However, this made the tissue unstable. “If you reduce the cross-linker density, the polymers no longer retain their organization during the expansion process,” said Boyden, who is a member of MIT’s Media Lab and McGovern Institute for Brain Research. “You lose the information.” Instead, in their latest study, the researchers modified their technique so that after the first tissue expansion, they can create a new gel that swells the tissue a second time — an approach they call “iterative expansion.” Using iterative expansion, the researchers were able to image tissues with a resolution of about 25 nanometers, which is similar to that achieved by high-resolution techniques such as stochastic optical reconstruction microscopy (STORM). However, expansion microscopy is much cheaper and simpler to perform because no specialized equipment or chemicals are required, Boyden says. The method is also much faster and thus compatible with large-scale, 3-D imaging. The resolution of expansion microscopy does not yet match that of scanning electron microscopy (about 5 nanometers) or transmission electron microscopy (about 1 nanometer). However, electron microscopes are very expensive and not widely available, and with those microscopes, it is difficult for researchers to label specific proteins. In the Nature Methods paper, the MIT team used iterative expansion to image synapses — the connections between neurons that allow them to communicate with each other. In their original expansion microscopy study, the researchers were able to image scaffolding proteins, which help to organize the hundreds of other proteins found in synapses. With the new, enhanced resolution, the researchers were also able to see finer-scale structures, such as the location of neurotransmitter receptors located on the surfaces of the “postsynaptic” cells on the receiving side of the synapse. “My hope is that we can, in the coming years, really start to map out the organization of these scaffolding and signaling proteins at the synapse,” Boyden said. Combining expansion microscopy with a new tool called temporal multiplexing should help to achieve that, he believes. Currently, only a limited number of colored probes can be used to image different molecules in a tissue sample. With temporal multiplexing, researchers can label one molecule with a fluorescent probe, take an image, and then wash the probe away. This can then be repeated many times, each time using the same colors to label different molecules. “By combining iterative expansion with temporal multiplexing, we could in principle have essentially infinite-color, nanoscale-resolution imaging over large 3-D volumes,” Boyden said. “Things are getting really exciting now that these different technologies may soon connect with each other.” The researchers also hope to achieve a third round of expansion, which they believe could, in principle, enable resolution of about 5 nanometers. However, right now the resolution is limited by the size of the antibodies used to label molecules in the cell. These antibodies are about 10 to 20 nanometers long, so to get resolution below that, researchers would need to create smaller tags or expand the proteins away from each other first and then deliver the antibodies after expansion. This study was funded by the National Institutes of Health Director’s Pioneer Award, the New York Stem Cell Foundation Robertson Award, the HHMI-Simons Faculty Scholars Award, and the Open Philanthropy Project.
News Article | April 27, 2017
Working with human brain tissue samples and genetically engineered mice, Johns Hopkins Medicine researchers together with colleagues at the National Institutes of Health, the University of California San Diego Shiley-Marcos Alzheimer's Disease Research Center, Columbia University, and the Institute for Basic Research in Staten Island say that consequences of low levels of the protein NPTX2 in the brains of people with Alzheimer’s disease (AD) may change the pattern of neural activity in ways that lead to the learning and memory loss that are hallmarks of the disease. This discovery, described online in the April 25 edition of eLife, will lead to important research and may one day help experts develop new and better therapies for Alzheimer’s and other forms of cognitive decline. AD currently affects more than five million Americans. Clumps of proteins called amyloid plaques, long seen in the brains of people with AD, are often blamed for the mental decline associated with the disease. But autopsies and brain imaging studies reveal that people can have high levels of amyloid without displaying symptoms of AD, calling into question a direct link between amyloid and dementia. This new study shows that when the protein NPTX2 is “turned down” at the same time that amyloid is accumulating in the brain, circuit adaptations that are essential for neurons to “speak in unison” are disrupted, resulting in a failure of memory. “These findings represent something extraordinarily interesting about how cognition fails in human Alzheimer’s disease,” says Paul Worley, M.D., a neuroscientist at the Johns Hopkins University School of Medicine and the paper’s senior author. “The key point here is that it’s the combination of amyloid and low NPTX2 that leads to cognitive failure.” Since the 1990s, Worley’s group has been studying a set of genes known as “immediate early genes,” so called because they’re activated almost instantly in brain cells when people and other animals have an experience that results in a new memory. The gene NPTX2 is one of these immediate early genes that gets activated and makes a protein that neurons use to strengthen “circuits” in the brain. “Those connections are essential for the brain to establish synchronized groups of ‘circuits’ in response to experiences,” says Worley. “Without them, neuronal activation cannot be effectively synchronized and the brain cannot process information.” Worley says he was intrigued by previous studies indicating altered patterns of activity in brains of individuals with Alzheimer’s. Worley’s group wondered whether altered activity was linked to changes in immediate early gene function. To get answers, the researchers first turned to a library of 144 archived human brain tissue samples to measure levels of the protein encoded by the NPTX2 gene. NPTX2 protein levels, they discovered, were reduced by as much as 90 percent in brain samples from people with AD compared with age-matched brain samples without AD. By contrast, people with amyloid plaques who had never shown signs of AD had normal levels of NPTX2. This was an initial suggestion of a link between NPTX2 and cognition. Prior studies had shown NPTX2 to play an essential role for developmental brain wiring and for resistance to experimental epilepsy. To study how lower-than-normal levels of NPTX2 might be related to the cognitive dysfunction of AD, Worley and his collaborators examined mice bred without the rodent equivalent of the NPTX2 gene. Tests showed that a lack of NPTX2 alone wasn’t enough to affect cell function as tested in brain slices. But then the researchers added to mice a gene that increases amyloid generation in their brain. In brain slices from mice with both amyloid and no NPTX2, fast-spiking interneurons could not control brain “rhythms” important for making new memories. Moreover, a glutamate receptor that is normally expressed in interneurons and essential for interneuron function was down-regulated as a consequence of amyloid and NPTX2 deletion in mouse and similarly reduced in human AD brain. Worley says that results suggest that the increased activity seen in the brains of AD patients is due to low NPTX2, combined with amyloid plaques, with consequent disruption of interneuron function. And if the effect of NPTX2 and amyloid is synergistic — one depending on the other for the effect — it would explain why not all people with high levels of brain amyloid show signs of AD. The team then examined NPTX2 protein in the cerebrospinal fluid (CSF) of 60 living AD patients and 72 people without AD. Lower scores of memory and cognition on standard AD tests, they found, were associated with lower levels of NPTX2 in the CSF. Moreover, NPTX2 correlated with measures of the size of the hippocampus, a brain region essential for memory that shrinks in AD. In this patient population, NPTX2 levels were more closely correlated with cognitive performance than current best biomarkers — including tau, a biomarker of neurodegenerative diseases, and a biomarker known as A-beta-42, which has long been associated with AD. Overall, NPTX2 levels in the CSF of AD patients were 36 to 70 percent lower than in people without AD. “Perhaps the most important aspect of the discovery is that NPTX2 reduction appears to be independent of the mechanism that generates amyloid plaques. This means that NPTX2 represents a new mechanism, which is strongly founded in basic science research, and that has not previously been studied in animal models or in the context of human disease. This creates many new opportunities,” says Worley. “One immediate application may be to determine whether measures of NPTX2 can be helpful as a way of sorting patients and identifying a subset that are most responsive to emerging therapies.” Worley says. For instance, drugs that disrupt amyloid may be more effective in patients with relatively high NPTX2. His group is now providing reagents to companies to assess development of a commercial test that measures NPTX2 levels. More work is needed, Worley adds, to understand why NPTX2 levels become low in AD and how that process could be prevented or slowed. In addition to Paul Worley, the study’s authors are Meifang Xiao, Desheng Xu, Chun-Che Chien, Yang Shi, Juhong Zhang, Olga Pletnikova, Alena Savonenko, Roger Reeves, and Juan Troncoso of Johns Hopkins University School of Medicine; Michael Craig of University of Exeter; Kenneth Pelkey and Chris McBain of the National Institute of Child Health and Human Development; Susan Resnick of the National Institute on Aging’s Intramural Research Program; David Salmon, James Brewer, Steven Edland, and Douglas Galasko of the Shiley-Marcos Alzheimer's Disease Research Center at the University of California San Diego Medical Center; Jerzy Wegiel of the Institute for Basic Research in Staten Island; and Benjamin Tycko of Columbia University Medical Center. Funding for the studies described in the eLife article was provided by the National Institutes of Health under grant numbers MH100024, R35 NS-097966, P50 AG005146, and AG05131, Alzheimer’s Disease Discovery Foundation and Lumind.
News Article | April 22, 2017
He’s known as one of the industry’s most talented musicians. But on Saturday, The Roots and Tonight Show drummer Questlove traded in the arts to preach about the importance of science at the March for Science in Washington, D.C. Co-hosting the Earth Day event, the 46-year-old musician and multi-instrumentalist (né Ahmir Khalib Thompson) spoke out against the new presidential administration’s reliance on “alternative facts” - saying that science should belong to the masses and that making it accessible to people is now more important than ever. “The rational scientific thought gets us out of the highest corners and to the most open, wide spaces,” he said, according to Time - before referring to President Donald Trump as “that guy over there.” “Many people seem to be forgetting those facts and it’s been frustrating to watch as certain forces in our society try to squelch science or their refusal to believe in it or propose alternative realities and facts. Alternative facts or whatever that (bleep) is. All that works against science and we need to work for science. More than that, we need to make sure science belongs to the people.” Questlove was speaking to a crowd of thousands of scientists and citizens at the event, which is a celebration of science and the real role it plays in politics and society. Aimed to “champion science as a pillar of human freedom and prosperity” and “advocate for its role in informing the policies that shape our present and future,” the grassroots event comes in the face of “an alarming trend toward discrediting scientific consensus and restricting scientific discovery,” its website reads. “People who value science have remained silent for far too long in the face of policies that ignore scientific evidence and endanger both human life and the future of our world,” the group wrote in their mission statement. “New policies threaten to further restrict scientists’ ability to research and communicate their findings. We face a possible future where people not only ignore scientific evidence, but seek to eliminate it entirely. Staying silent is a luxury that we can no longer afford. We must stand together and support science.” RELATED VIDEO: Bill Nye At The March For Science: “Together we can save the world” While the application of science to policy is a non-partisan issue, the Trump administration has proposed budget cuts to the Environmental Protection Agency and the National Institutes of Health. But the problem is much bigger than Trump. Bill Nye the Science Guy star Bill Nye stressed the problem goes well beyond the United States government. “Without scientifically literate citizens, the United States - and country in fact - cannot compete on the world stage,” he said. “Yet today we have a great many lawmakers, not just here but around the world, deliberately ignoring and actively suppressing science. Their inclination is misguided and in no one’s best interest. Our lives are in every way improved by having clean water, reliable electricity, and access to electronic global information.” “Some may consider science the purview of a special or separate type of citizen,” he continued. “One who pursues natural facts and generates numerical models for their own sakes. But our numbers here today show the world that science is for all. Our lawmakers must know and accept that science serves every one of us. Every citizen of every nation and society. Science must shape policy. Science is universal. Science brings out the best of us.” The 61-year-old star ended his speech on a hopeful note. “With an informed, optimistic view of the future together we can, dare I say it, save the world!” he said, to the cheers of the crowd. The March of Science kicked off at 9 a.m. with a teach-in and rally - where Mona Hanna-Attisha, the pediatrician responsible for exposing the water crisis in Flint, Michigan, also spoke. Co-hosted with the Earth Day Network, the event ended with a march through the streets of D.C. And though this was a day about science, there was some art after all when Thomas Dolby gave a live performance of his 1982 hit “She Blinded Me with Science” - as seen on Questlove’s Instagram page. Trump has not yet commented on the March for Science but did comments about Earth Day on Twitter. “Today on Earth Day, we celebrate our beautiful forests, lakes and land,” he wrote. “We stand committed to preserving the natural beauty of our nation.” This article was originally published on PEOPLE.com
News Article | May 1, 2017
PITTSBURGH, May 1, 2017 - A novel gene therapy using CRISPR genome editing technology effectively targets cancer-causing "fusion genes" and improves survival in mouse models of aggressive liver and prostate cancers, University of Pittsburgh School of Medicine researchers report in a study published online today in Nature Biotechnology. "This is the first time that gene editing has been used to specifically target cancer fusion genes. It is really exciting because it lays the groundwork for what could become a totally new approach to treating cancer," explained lead study author Jian-Hua Luo, M.D., Ph.D., professor of pathology at Pitt's School of Medicine and director of its High Throughput Genome Center. Fusion genes, which often are associated with cancer, form when two previously separate genes become joined together and produce an abnormal protein that can cause or promote cancer. Luo and his team had previously identified a panel of fusion genes responsible for recurrent and aggressive prostate cancer. In a study published earlier this year in the journal Gastroenterology, the team reported that one of these fusion genes, known as MAN2A1-FER, also is found in several other types of cancer, including that of the liver, lungs and ovaries, and is responsible for rapid tumor growth and invasiveness. In the current study, the researchers employed the CRISPR-Cas9 genome editing technology to target unique DNA sequences formed because of the gene fusion. The team used viruses to deliver the gene editing tools that cut out the mutated DNA of the fusion gene and replaced it with a gene that leads to death of the cancer cells. Because the fusion gene is present only in cancer cells, not healthy ones, the gene therapy is highly specific. Such an approach could come with significantly fewer side effects when translated to the clinic, which is a major concern with other cancer treatments such as chemotherapy. To conduct the study, the researchers used mouse models that had received transplants of human prostate and liver cancer cells. Editing the cancer fusion gene resulted in up to 30 percent reduction in tumor size. None of the mice exhibited metastasis and all survived during the eight-week observation period. In contrast, in control mice treated with viruses designed to cut out another fusion gene not present in their tumors, the tumors increased nearly 40-fold in size, metastasis was observed in most animals, and all died before the end of the study. The new findings suggest a completely new way to combat cancer. "Other types of cancer treatments target the foot soldiers of the army. Our approach is to target the command center, so there is no chance for the enemy's soldiers to regroup in the battlefield for a comeback," said Luo. Another advantage over traditional cancer treatment is that the new approach is very adaptive. A common problem that renders standard chemotherapies ineffective is that the cancer cells evolve to generate new mutations. Using genome editing, the new mutations could be targeted to continue fighting the disease, Luo noted. In the future, the researchers plan to test whether this strategy could completely eradicate the disease rather than induce the partial remission observed in the current study. This work was supported by National Institutes of Health grant RO1 CA098249, Department of Defense grant W81XWH-16-1-0364 and a grant from the University of Pittsburgh Cancer Institute. Additional authors include: Zhang-Hui Chen, Ph.D., Yan Yu, M.D., Ph.D., Ze-Hua Zuo, Ph.D., Joel Nelson, M.D., George Michalopoulos, M.D., Ph.D., Satdatshan Monga, M.D., Silvia Liu, B.S., and George Tseng, Sc.D., all of Pitt. About the University of Pittsburgh School of Medicine As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support. Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see http://www. .
News Article | April 17, 2017
Our world seems to grow smaller by the day as biodiversity rapidly dwindles, but Mother Earth still has a surprise or two up her sleeve. An international team of researchers were the first to investigate a never before studied species -- a giant, black, mud dwelling, worm-like animal. The odd animal doesn't seem to eat much, instead it gets its energy from a form of sulfur. The findings, led by scientists at the University of Utah, Northeastern University, University of the Philippines, Sultan Kudarat State University and Drexel University, will be published online in the Apr. 17 issue of the Proceedings of the National Academy of Sciences. People have known about the existence of the creature for centuries. The three- to five-foot long, tusk-like shells that encase the animal were first documented in the 18th century. "The shells are fairly common," begins lead investigator Daniel Distel, Ph.D., a research professor and director of the Ocean Genome Legacy Center at Northeastern University, "But we have never had access to the animal living inside." The animal's preferred habitat was unclear, but the research team benefitted from a bit of serendipity when one of their collaborators shared a documentary that aired on Philippine television. The video showed the bizarre creatures planted, like carrots, in the mud of a shallow lagoon. Following this lead, the scientists set up an expedition and found live specimens of Kuphus polythalamia. With a live giant shipworm finally in hand, the research team huddled around Distel as he carefully washed the sticky mud caked to the outside of the giant shipworm shell and tapped off the outer cap, revealing the creature living inside. "I was awestruck when I first saw the sheer immensity of this bizarre animal," says Marvin Altamia, researcher at the marine sciences institute, University of the Philippines. "Being present for the first encounter of an animal like this is the closest I will ever get to being a 19th century naturalist," says the study's senior author Margo Haygood, a research professor in medicinal chemistry at the University of Utah College of Pharmacy. Because the animal had never been studied rigorously, little was known about its life history, habitat, or biology. "We suspected the giant shipworm was radically different from other wood-eating shipworms," says Haygood. "Finding the animal confirmed that." Altamia continues, "Frankly, I was nervous. If we made a mistake, we could lose the opportunity to discover the secrets of this very rare specimen." The scientists were then faced with an interesting dilemma explain why Kuphus is so unusual. The answer may lie in the remote habitat in which it was found, a lagoon laden with rotting wood. The normal shipworm burrows deep into the wood of trees that have washed into the ocean, munching on and digesting the wood with the help of bacteria. Unlike its shipworm cousins, Kuphus lives in the mud. It also turns to bacteria to obtain nourishment, but in a different way. Kuphus lives in a pretty stinky place. The organic-rich mud around its habitat emits hydrogen sulfide, a gas derived from sulfur, which has a distinct rotten egg odor. This environment may be noxious for you and me, but it is a feast for the giant shipworm. And yet Kuphus themselves don't eat, or if they do, they eat very little. Instead, they rely on beneficial bacteria that live in their gills that make food for them. Like tiny chefs, these bacteria use the hydrogen sulfide as energy to produce organic carbon that feeds the shipworm. This process is similar to the way green plants use the sun's energy to convert carbon dioxide in the air into simple carbon compounds during photosynthesis. As a result, many of Kuphus's internal digestive organs have shrunk from lack of use. The giant shipworm's lifestyle lends support to a hypothesis proposed by Distel almost two decades ago. Acquiring a different type of beneficial bacteria could explain how shipworms transition from a wood-eating organism to one that uses a noxious gas in mud to survive. The research team will continue to examine the role wood plays in the unique transition between the normal shipworm and the giant shipworm. "We are also interested to see if similar transitions can be found for other animals that live in unique habitats around the world," said Distel. The discovery of this flagship creature expands on our understanding of biodiversity in the Indo-Pacific region, which was made possible through collaborative nature of this interdisciplinary, international research group. This work is an important component of research grants provided by the International Cooperative Biodiversity Groups program. The program helps researchers conduct projects in developing countries to identify unique, novel compounds for future drug development, while building research capacity and conserving biodiversity in the host country. Distel and Haygood collaborated with colleagues from University of Utah, Drexel University, Second Genome in San Francisco, Ecole Normale Superieure, France and the University of the Philippines, the Sultan Kudarat State University and the Philippine Genome Center in the Philippines. The research was funded by National Institutes of Health, National Science Foundation and U.S Department of Energy, Joint Genome Institute.
News Article | April 24, 2017
Gut bacteria could influence whether or not babies survive infections of the digestive system, new research with mice suggests. Hundreds of thousands of babies worldwide die every year from infections that ravage their digestive systems, including those caused by salmonella and E. coli bacteria. Millions more children get sick. The bacteria Clostridia provide animals key protection against infection, in addition to helping digest food. But the data show the youngest newborn mice don’t have Clostridia yet, making them the most vulnerable to invading bacteria similar to those that sicken so many human babies. The findings, published in Science, could point to new approaches to protect human babies. “Any parent knows that newborns are very susceptible to infections in the first year of life, including enteric, or gut, infections,” says Gabriel Nunez, the study’s senior author and a pathology professor at the University of Michigan Medical School. “This work suggests that the lack of protective bacteria in the gut microbiota is a mechanism for that susceptibility, perhaps more than the age of the immune system.” Germ-free mice Nunez and his colleagues, including co-first authors and research fellows Yun-Gi Kim and Kei Sakamoto, started with a blank slate: mice bred in a germ-free environment. With no natural gut bacteria of their own, the mice offered a unique chance to see the effects of transplanted microbes from normal mice of different ages and to test vulnerability to infection. The researchers also used advanced DNA analysis techniques to detect the types and amounts of bacteria in mouse guts. The bottom line: Somewhere in the period around weaning mice from mother’s milk onto solid food, Clostridia bacteria begin to grow in the gut and work to prevent the growth of two forms of illness-causing bacteria. The research team used both newborn and adult germ-free mice and samples of gut microbes taken from the feces of 4-day-old, 12-day-old, and 16-day-old normal mice for the experiments. They found that the samples from the older normal mice had the most diversity of gut microbes, including Clostridia and Bacteroides bacteria not seen in the younger mice that were still getting their nutrition entirely from mother’s milk. First, the researchers gave the germ-free mice a transplant of bacteria from 4-day-old or 16-day-old normal mice and then exposed them to a strain of salmonella that can infect the gut but not spread bodywide. Half the mice that got the 4-day-old microbes died, but none of those with 16-day-old microbes did. New clues to why intestines of preemies stop working They tried it again with Citrobacter rodentium, a strain of bacteria similar to the E. coli strains that make humans sick. Germ-free mice with transplanted four-day-old microbes got sick, and many died. But when the researchers added bacteria from 16-day-old normal mice, the amount of C. rodentium in the guts of surviving mice went down. Next, the researchers looked at what happened to germ-free mice that had been given a newborn mouse’s microbes, but with extra doses of either Clostridia or Bacteroides bacteria added in. They exposed groups of these mice to C. rodentium and found that only the mice given Clostridia were able to resist the infections. After a week, 90 percent of the mice that got extra Clostridia, then salmonella, were still alive, compared with 50 percent of those that hadn’t received it. Because E. coli and salmonella also affect adults, the researchers tested what happened when normal adult mice were given vancomycin, an antibiotic that selectively kills bacteria like Clostridia and Bacteroides. Both C. rodentium and salmonella flourished in these environments. Added defense To see what role the body’s own immune system played in fighting infection compared with gut microbes, the team also studied two strains of mice that have impaired immune systems. Raised in a germ-free environment and then given a transplant of gut microbes from a four-day-old normal mouse, these mice were still able to resist salmonella infection without any help from their immune system—but only when they had received a dose of added Clostridia first. Finally, the researchers looked at the impact of adding succinate—a salt that oxygen-loving bacteria in the gut produce as a byproduct—into the drinking water of germ-free mice with four-day-old microbes that had received extra Clostridia. These mice fought off salmonella infection even better, suggesting that the anaerobic Clostridia feed off the waste products of the aerobic bacteria that flourish in the guts of newborns. Nunez and his colleagues are working on further research on the role of Clostridia in defending against gut infections. They want to determine which strains of Clostridia—and there are many—have the largest effect. Gut bacteria of preemies raise concerns about antibiotics They’re also looking at the role of mother’s milk in establishing a newborn’s gut microbiome and conveying protection from infection, as well as the transition to solid foods that can carry microbes into a newborn’s gut from the outside world. And they want to test whether other components of the microbiome protect against other pathogens. “Normally, we acquire Clostridia strains in our guts when we begin to eat solids, but this work suggests a window of vulnerability to enteric pathogens in the early stages of life,” says Nunez. He says that if the protective role of added Clostridia for newborns bears out in further animal studies, it might be possible to propose a clinical trial in humans to test a combination of strains. Nunez, Kim, Sakamoto, and their colleagues from the University of Michigan, the University of Chicago, and universities in Japan and Korea performed the work using funding from the National Institutes of Health. Source: University of Michigan The post These gut microbes may protect babies from infections appeared first on Futurity.
News Article | May 1, 2017
Bottom Line: A noninvasive PET imaging method that measures granzyme B, a protein released by immune cells to kill cancer cells, was able to distinguish mouse and human tumors that responded to immune checkpoint inhibitors from those that did not respond early in the course of treatment. Journal in Which the Study was Published: Cancer Research, a journal of the American Association for Cancer Research. Author: Umar Mahmood, MD, PhD, professor of radiology at Harvard Medical School and director of the Division of Precision Medicine at Athinoula A. Martinos Center for Biomedical Imaging in Massachusetts General Hospital (MGH), Boston. Background: Although immunotherapies, such as checkpoint inhibitors, have revolutionized cancer treatment, they only work in a minority of patients, which means that most patients receiving this treatment will not benefit but still have the increased risk of side effects, besides losing time that they could spend on other therapies, Mahmood explained. Response to immunotherapy often cannot be measured effectively at early time points by traditional imaging techniques that measure tumor size, such as CT and MRI scans, or those that measure tumor glucose uptake, such as FDG PET, because these techniques cannot distinguish a nonresponding tumor from a tumor that is responding to immunotherapy but appears to grow in size because it is filled with immune cells and accompanied by increased glucose uptake, Mahmood noted. Tissue biopsies can be unreliable because of tumor heterogeneity and constant changes in the levels of the biomarker proteins measured. How the Study Was Conducted: Mahmood and colleagues designed a probe that binds to granzyme B--a protein that immune cells release to kill their target--after it is released from the immune cells, so they could directly measure tumor cell killing. The researchers attached the probe to a radioactive atom and used PET scanning to noninvasively image the entire body and see where immune cells are actively releasing tumor-killing granzyme B. Results:The team tested their probe in tumor-bearing mice before and after treatment with immune checkpoint inhibitors and found that one group of mice had high PET signal, meaning high levels of granzyme B in the tumors, while the other group had low levels of PET signal in the tumors. When the two groups of mice were followed, all mice with high PET signal responded to the therapy and their tumors subsequently regressed, whereas those with low PET signal did not respond to the therapy, and their tumors continued to grow. "Because PET imaging is quantitative, we could measure the degree of effectiveness and put a number on it," Mahmood added. When they compared the data from monotherapy and combination therapy, they saw a significant increase in tumor granzyme B PET signal in the combination group. The researchers then collaborated with Keith Flaherty, MD, and Genevieve Boland, MD, PhD, from MGH, and tested their probe on nine human melanoma biopsy samples, six from patients treated with nivolumab (Opdivo) and three from those treated with pembrolizumab (Keytruda). They detected high levels of granzyme B in the samples from responders and much lower levels in the samples from nonresponders. Author Comment: "The ability to differentiate early in the course of treatment patients who are likely to benefit from immunotherapy from those who will not can greatly improve individual patient care and help accelerate the development of new therapies," Mahmood said. "In our study, we found a marker that was highly predictive of response to immunotherapy at a very early time after starting treatment, and we were able to design an imaging probe to detect this marker and accurately predict response noninvasively," said Mahmood. "These findings could have a significant impact on drug development, as different combinations could be imaged at very early time points in patients and the levels of tumor granzyme B used to compare treatments and rank effectiveness," Mahmood said. "Further, therapeutics that achieve high levels of granzyme B release can be advanced faster and those leading to low granzyme B release can be altered or eliminated." Limitations: A limitation of the study is that the probe has not yet been tested in the clinic, but the researchers are actively pursuing it, Mahmood noted. Funding & Disclosures: This study was funded by the National Institutes of Health. Mahmood is the cofounder and consultant at CytoSite BioPharma, a company that is further developing the granzyme B PET imaging probe for clinical translation. Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 37,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and patient advocates residing in 108 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 30 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 21,900 attendees. In addition, the AACR publishes eight prestigious, peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual investigator grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and other policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit http://www. .
News Article | April 20, 2017
A Massachusetts General Hospital (MGH)-led research team has identified a surprising new role for macrophages, the white blood cells primarily known for removing pathogens, cellular debris and other unwanted materials. In their paper published in Cell the investigators describe discovering that macrophages are also essential to the healthy functioning of the heart, helping conduct the electric signals that coordinate the heartbeat. "Our finding that a new cell type is involved in cardiac conduction may lead to better understanding of normal heart function. What really surprised me was that macrophages can depolarize -- change their electric charge -- when coupled to a myocyte. Down the line, this work on the role of macrophages in conduction may lead to new treatments for cardiac arrhythmias," says corresponding author Matthias Nahrendorf, MD, PhD, of the MGH Center for Systems Biology. Best known for their immune system activity of engulfing and digesting microbes, damaged cells and foreign substances, macrophages are found in tissues throughout the body and have recently been shown to have additional functions related to the tissues where they reside. While macrophages are required for healing damaged tissues in the heart, their presence within healthy heart muscle suggests a role in normal heart function. Nahrendorf's study was designed to investigate their potential role in transmitting and coordinating the electrical signals that stimulate heart muscle contraction. Initial experiments in mice revealed that cardiac macrophages are more abundant in the atrioventicular (AV) node -- a key structure connecting the atria (upper chambers) to the ventricles (lower chambers) -- which coordinates contraction timing for the upper and lower chambers. Similarly high concentrations of macrophages were found in AV nodes from human autopsy samples. Subsequent animal experiments found that macrophages connect to heart muscle cells via gap junctions -- pore-like structures known to coordinate heart muscle contractions -- and that the shifts in electric charge that carry the conduction signal are synchronized between macrophages and adjacent heart muscle cells called myocytes. Mice lacking a key gap junction protein showed an abnormal slowing of signal conduction through the AV node, and a complete depletion of tissue macrophages led to the development of AV block -- a delay in conduction between the atria and ventricles that, in human patients, requires pacemaker implantation. Overall, the findings suggest that cardiac macrophages are essential participants in the cardiac conduction system and that changes in their numbers or properties may contribute to heart rhythm abnormalities. Nahrendorf and his colleagues are continuing to explore the role of macrophages in both the healthy heart and in common disorders of signal conduction. He adds that the cells' natural propensity to surround and take up materials for disposal could be used to induce macrophages to ingest drugs carried on nanoparticles. The co-lead authors of the Cell paper are Maarten Hulsmans, PhD, of the MGH Center for Systems Biology and Sebastian Clauss, MD, and Ling Xiao, PhD, of the MGH Cardiovascular Research Center. Additional co-authors include David Milan, MD, and Patrick Ellinor, MD, PhD, of the CVRC. Support for the study includes National Institutes of Health grants NS084863, HL128264, HL114477, HL117829, HL092577, HL105780, and HL096576. The MGH has filed a patent application covering the work described in this paper. Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $800 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, genomic medicine, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2016 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of "America's Best Hospitals."
News Article | April 17, 2017
The newest exhibit on display at the University City Science Center’s Esther Klein Gallery (EKG) is a retrospective by sculptor Rebecca Kamen, featuring a collaborative multi-media installation that explores the relationship between inner and outer space. Continuum opens on April 13th and runs through May 27th. An opening reception featuring a dance performance by Megan Mizanty will be held at EKG on April 13th from 5 to 7:30 p.m. Among the pieces in the exhibit is NeuroCantos, a collaboration between Kamen, sound artist Susan Alexjander, and poet Steven J. Fowler. The installation investigates how the brain distinguishes between inner and outer space through its ability to perceive similar patterns of complexity at the micro and macro scale. The piece is made up of cone-shaped structures representing the neuronal networks in the brain with overlapping shapes and rocks that symbolize art’s ability to form bridges of understanding between diverse fields. Continuum also features works inspired by Kamen’s residencies at the American Philosophical Society Library and the Chemical Heritage Foundation. Kamen’s work is informed by wide-ranging research into cosmology, history, philosophy, and by connecting common threads that flow across various scientific fields to capture and re-imagine what scientists see. Rebecca Kamen has exhibited and lectured both nationally and internationally including China, Hong Kong, Korea, Austria, Chile, Egypt, Spain, and Australia. She has been the recipient of a Virginia Museum of Fine Arts Professional Fellowship, a Pollack Krasner Foundation Fellowship, two Strauss Fellowships, and a Travel Grant from the Chemical Heritage Foundation. As artist-in-residence in the neuroscience program at National Institutes of Health, Kamen has interpreted and transformed neuroscience research into sculptural form. Her artwork is represented in many private and public collections. Located in the heart of uCity Square, the Science Center is a mission-driven nonprofit organization that catalyzes and connects innovation to entrepreneurship and technology commercialization. For 50+ years, the Science Center has supported startups, research, and economic development in the life sciences, healthcare, physical sciences, and emerging technology sectors. As a result, graduate firms and current residents of the Science Center’s incubator support one out of every 100 jobs in the Greater Philadelphia region and drive $13 billion in economic activity in the region annually. By providing resources and programming for any stage of a business’s lifecycle, the Science Center helps scientists, entrepreneurs and innovators take their concepts from idea to IPO – and beyond. For more information about the Science Center, go to http://www.sciencecenter.org The Esther Klein Gallery (EKG), which opened in 1977, uses the creative arts as a platform to explore relationships between art, science and technology. EKG seeks to positively impact the cultural life of both its immediate neighborhood of West Philadelphia and the broader Philadelphia community. EKG programming is designed to explore the range of art, science and technology exhibitions, and includes gallery talks, panel discussions, and education programs. For more information, visit http://www.sciencecenter.org/discover/ekg.
News Article | April 24, 2017
ANAHEIM, CA / ACCESSWIRE / April 24, 2017 / BioCorRx Inc. (OTCQB: BICX) (the "Company"), a developer and provider of advanced solutions in the treatment of substance use disorders, today announced it entered into an agreement with DynamiCare Health™, Inc. to develop a co-branded mobile application to support patients engaged in counseling for the treatment of alcoholism or opioid addiction and receiving long-term naltrexone treatment. DynamiCare Health is focused on building evidence-based tools that motivate people to live healthy lives. The mobile application, DynamiCare Rewards™ with BioCorRx CBT, is being designed to offer patients a self-guided, interactive version of BioCorRx's proprietary, naltrexone specific, Cognitive Behavioral Therapy (CBT) program. The CBT program, in its current form, has been in use since 2015 by addiction counselors across the country as part of the company's comprehensive BioCorRx® Recovery Program. The platform will enable counselors to remotely monitor the progress of their patients as they complete the program modules. The BioCorRx program consists of 35 modules developed by addiction experts with years of experience counseling individuals receiving long term naltrexone therapy. DynamiCare Health will service the backend data provided by BioCorRx and provide a rewards system and reminder system to keep patients engaged in counseling. Brady Granier, President, CEO and Director stated, "The agreement with DynamiCare Health marks an important step to advance our addiction recovery program virtually anywhere. We are proud of the results that independent treatment providers and their patients have been experiencing with our naltrexone specific, medication assisted treatment (MAT) program over the last few years. We look forward to collaborating with the founders of DynamiCare Health, David R. Gastfriend, MD and Eric Gastfriend, MBA, who bring extensive experience in the addiction market and mobile technologies, respectively. With this new technology platform, we believe that we can elevate our program to a new level to better serve our domestic partners and their patients, while creating potential new opportunities abroad. We look forward to seeing our counseling modules become tangible, interactive, and engaging via a mobile application. The development has already begun and we hope to receive the first version for testing this Summer." Eric Gastfriend, co-founder of DynamiCare Health, commented, "We look forward to working closely with BioCorRx to develop a first-in-kind mobile application intended to support substance abuse treatment, creating a scalable tool that can improve outcomes and effectively measure results. We believe this revolutionary telemedicine drug recovery program has the potential to broadly transform the treatment of alcoholism and opioid addiction by combining cutting-edge medicine, behavioral science, and mobile technology." About BioCorRx BioCorRx Inc. (OTCQB: BICX) is an addiction treatment company offering a unique approach to the treatment of substance abuse addiction. The BioCorRx® Recovery Program, a non-addictive, medication-assisted treatment (MAT) program, consists of two main components. The first component of the program consists of an outpatient implant procedure performed by a licensed physician. The implant delivers the non-addictive medicine, naltrexone, an opioid antagonist that can significantly reduce physical cravings for alcohol and opioids. The second component of the program developed by BioCorRx Inc. is a one-on-one counseling program specifically tailored for the treatment of alcoholism and other substance abuse addictions for those receiving long-term naltrexone treatment. The Company also has an R&D subsidiary, BioCorRx Pharmaceuticals, which is currently developing a new injectable naltrexone technology (BICX101) through a partnership with TheraKine Ltd. The company plans to seek FDA approval for BICX101 and/or its naltrexone implant product(s). For more information on BICX, visit www.BioCorRx.com. About DynamiCare Health DynamiCare Health, Inc. is a Boston-based tech startup building a mobile platform to assist healthcare providers and patients with addiction recovery. DynamiCare Rewards™, the company's first product, is a set of tools for patients who want to focus and sustain their sobriety efforts by using state-of-the-art behavioral rewards. Based on the psychological model of operant conditioning, the use of incentives in addiction treatment, Contingency Management, is recommended by the U.S. Surgeon General, the American Society of Addiction Medicine, and the National Institutes of Health. The company was founded in May 2016 by David R. Gastfriend MD, a leading expert in addiction psychiatry, and his son Eric Gastfriend, former General Manager of the venture-backed cloud gaming startup Happy Cloud and a Harvard Business School MBA. Safe Harbor Statement The information in this release includes forward-looking statements. These forward-looking statements generally are identified by the words "believe," "project," "estimate," "become," "plan," "will," and similar expressions. These forward-looking statements involve known and unknown risks as well as uncertainties. Although the Company believes that its expectations are based on reasonable assumptions, the actual results that the Company may achieve may differ materially from any forward-looking statements, which reflect the opinions of the management of the Company only as of the date hereof. BioCorRx Inc. investors@BioCorRx.com 714-462-4880 Investor Relations: Crescendo Communications, LLC BICX@crescendo-ir.com 212-671-1020 x304 SOURCE: BioCorRx Inc. ReleaseID: 460265April 24, 2017 /AccessWire/ — ANAHEIM, CA / ACCESSWIRE / April 24, 2017 / BioCorRx Inc. (OTCQB: BICX) (the "Company"), a developer and provider of advanced solutions in the treatment of substance use disorders, today announced it entered into an agreement with DynamiCare Health™, Inc. to develop a co-branded mobile application to support patients engaged in counseling for the treatment of alcoholism or opioid addiction and receiving long-term naltrexone treatment. DynamiCare Health is focused on building evidence-based tools that motivate people to live healthy lives. The mobile application, DynamiCare Rewards™ with BioCorRx CBT, is being designed to offer patients a self-guided, interactive version of BioCorRx's proprietary, naltrexone specific, Cognitive Behavioral Therapy (CBT) program. The CBT program, in its current form, has been in use since 2015 by addiction counselors across the country as part of the company's comprehensive BioCorRx® Recovery Program. The platform will enable counselors to remotely monitor the progress of their patients as they complete the program modules. The BioCorRx program consists of 35 modules developed by addiction experts with years of experience counseling individuals receiving long term naltrexone therapy. DynamiCare Health will service the backend data provided by BioCorRx and provide a rewards system and reminder system to keep patients engaged in counseling. Brady Granier, President, CEO and Director stated, "The agreement with DynamiCare Health marks an important step to advance our addiction recovery program virtually anywhere. We are proud of the results that independent treatment providers and their patients have been experiencing with our naltrexone specific, medication assisted treatment (MAT) program over the last few years. We look forward to collaborating with the founders of DynamiCare Health, David R. Gastfriend, MD and Eric Gastfriend, MBA, who bring extensive experience in the addiction market and mobile technologies, respectively. With this new technology platform, we believe that we can elevate our program to a new level to better serve our domestic partners and their patients, while creating potential new opportunities abroad. We look forward to seeing our counseling modules become tangible, interactive, and engaging via a mobile application. The development has already begun and we hope to receive the first version for testing this Summer." Eric Gastfriend, co-founder of DynamiCare Health, commented, "We look forward to working closely with BioCorRx to develop a first-in-kind mobile application intended to support substance abuse treatment, creating a scalable tool that can improve outcomes and effectively measure results. We believe this revolutionary telemedicine drug recovery program has the potential to broadly transform the treatment of alcoholism and opioid addiction by combining cutting-edge medicine, behavioral science, and mobile technology." About BioCorRx BioCorRx Inc. (OTCQB: BICX) is an addiction treatment company offering a unique approach to the treatment of substance abuse addiction. The BioCorRx® Recovery Program, a non-addictive, medication-assisted treatment (MAT) program, consists of two main components. The first component of the program consists of an outpatient implant procedure performed by a licensed physician. The implant delivers the non-addictive medicine, naltrexone, an opioid antagonist that can significantly reduce physical cravings for alcohol and opioids. The second component of the program developed by BioCorRx Inc. is a one-on-one counseling program specifically tailored for the treatment of alcoholism and other substance abuse addictions for those receiving long-term naltrexone treatment. The Company also has an R&D subsidiary, BioCorRx Pharmaceuticals, which is currently developing a new injectable naltrexone technology (BICX101) through a partnership with TheraKine Ltd. The company plans to seek FDA approval for BICX101 and/or its naltrexone implant product(s). For more information on BICX, visit www.BioCorRx.com. About DynamiCare Health DynamiCare Health, Inc. is a Boston-based tech startup building a mobile platform to assist healthcare providers and patients with addiction recovery. DynamiCare Rewards™, the company's first product, is a set of tools for patients who want to focus and sustain their sobriety efforts by using state-of-the-art behavioral rewards. Based on the psychological model of operant conditioning, the use of incentives in addiction treatment, Contingency Management, is recommended by the U.S. Surgeon General, the American Society of Addiction Medicine, and the National Institutes of Health. The company was founded in May 2016 by David R. Gastfriend MD, a leading expert in addiction psychiatry, and his son Eric Gastfriend, former General Manager of the venture-backed cloud gaming startup Happy Cloud and a Harvard Business School MBA. Safe Harbor Statement The information in this release includes forward-looking statements. These forward-looking statements generally are identified by the words "believe," "project," "estimate," "become," "plan," "will," and similar expressions. These forward-looking statements involve known and unknown risks as well as uncertainties. Although the Company believes that its expectations are based on reasonable assumptions, the actual results that the Company may achieve may differ materially from any forward-looking statements, which reflect the opinions of the management of the Company only as of the date hereof. BioCorRx Inc. investors@BioCorRx.com 714-462-4880 Investor Relations: Crescendo Communications, LLC BICX@crescendo-ir.com 212-671-1020 x304 SOURCE: BioCorRx Inc. ReleaseID: 460265 Source URL: http://marketersmedia.com/biocorrx-collaborating-with-dynamicare-health-to-develop-mobile-application-for-patients-with-opioid-and-alcohol-addiction/189546Source: AccessWireRelease ID: 189546