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News Article | April 24, 2017
Site: www.eurekalert.org

Researchers at UConn Health used stem cells derived from patients with Angelman syndrome to identify the underlying cellular defects that cause the rare neurogenetic disorder, an important step in the ongoing search for potential treatments for Angelman and a possible cure. Up until now, scientists trying to understand why the brain cells of individuals with Angelman fail to develop properly have relied primarily on mouse models that mimic the disorder. By using human stem cells that are genetically identical to the brain cells of Angelman syndrome patients, researchers now have a much clearer and more accurate picture of what is going wrong. In a study appearing April 24 in the journal Nature Communications, the researchers report that the brain cells of individuals with Angelman syndrome fail to properly mature, causing a cascade of other developmental deficits that result in Angelman syndrome. "We looked at the electrical activity of these brain cells and their ability to form connections, which is critical to the working circuits in the brain," says UConn Health neuroscientist Eric Levine, the study's lead author. "We found that the cells from Angelman patients had impairments," says Levine. "They didn't develop the same way as they do in people who don't have the disorder. They failed to develop mature electrical activity and they didn't form connections as readily." Angelman syndrome appears in one out of every 15,000 live births. People with Angelman have developmental delays, are prone to seizures, and can have trouble walking or balancing. They have limited speech, but generally present a happy demeanor, frequently laughing and smiling. The disorder occurs when a single gene that individuals inherit from their mother's 15th chromosome is deleted or inactive. The paternal copy of that gene, known as UBE3A, is normally silenced in brain cells. The research study led by Levine was done in collaboration with another research team at UConn Health led by developmental geneticist Stormy Chamberlain. Chamberlain is investigating the underlying genetic mechanisms that cause Angelman and how they might be reversed. Levine's research team meanwhile is looking at the physiology behind the disorder or what happens in the brain when the maternal UBE3A gene is missing or fails to work properly. "What's interesting about this particular study is that Eric captured some of the first electrophysiological differences between Angelman syndrome neurons and typically developing neurons and it appears those primary deficits are setting up all of the other problems that are happening downstream," says Chamberlain. The human brain relies on electrical signals to process information. These signals pass between the neurons in our brain via special connections called synapses. In the current study, Levine found that at about three to five weeks into their development, brain cells in unaffected individuals ramp up their electrical activity while cells from Angelman patients do not. This failure to mature disrupts the ability of the Angelman cells to form proper synaptic connections, which is critical for learning, memory, and cognitive development. "Other researchers haven't seen this deficit in mouse models, but we think it might have some-thing to do with where they were looking," says Chamberlain, who is a co-author on the current study. "In the mouse studies, researchers have been looking at either adults, juvenile, or early postnatal neurons. Eric is looking at some of the earliest changes in neurons that likely occur during fetal development." Angelman patients are very active in the ongoing research into the disorder. The induced pluripotent stem cells used in Levine's research were derived from skin and blood cells donated by people with Angelman. Those cells were then reprogrammed into stem cells that were grown in the lab into brain cells that match the patient's genetic makeup. This process allowed Levine to closely monitor how the cells developed from their very earliest stages in vitro and to see how they differed from control cells taken from people without the disorder. To confirm that the cellular defects in the Angelman cells were caused by the loss of the UBE3A gene, Levine edited out the UBE3A gene in cells from the control group to see what would happen. Indeed, the same cascading chain of events occurred. "In the control subjects who did not have Angelman, we basically knocked out the gene in order to mimic the Angelman defect," Levine says. "If you do that early enough in development, you see all of the things go wrong in those cells. Interestingly, if you wait and knock out the gene later in development, you only see a subset of those deficits." Those results led Levine to believe that the delayed development of electrical activity in the brain cells from patients with Angelman is one of the driving factors causing other defects to occur. That knowledge is important for the development of possible drugs to combat Angelman. If scientists can stop that initial electrical failure from happening, it might prevent the other developmental problems from happening as well. Researchers with Ionis Pharmaceuticals from Carlsbad, Calif. also participated in the current study. With this new information in hand, Chamberlain and Levine are taking the research to the next level. They want to know exactly how the loss of the UBE3A gene causes the development of electrical activity in the early brain cells of Angelman patients to stop. Another benefit of the current study is that the stem cell model created by Chamberlain and Levine can now be used to screen potential therapeutics for Angelman. Having the ability to monitor human brain cells in the lab will allow researchers to test dozens if not hundreds of compounds to see if they reverse Angelman's cellular defects. The same process could be applied by scientists looking into other disorders. "The Angelman Syndrome Foundation was proud to fund Dr. Levine's research in 2011 and we are thrilled to see the results," says Eileen Braun, executive director of the national nonprofit organization that funds Angelman syndrome research and supports individuals with Angelman and their families. "Having results published in Nature Communications, a prestigious, peer-reviewed journal, illustrates the validity of this research, which ultimately helps us understand more about Angelman syndrome and helps lead us to our ultimate goal of treatments and a cure."


There’s a whole lot more to colon cancer prevention than just colonoscopy. A key here is understanding the progression of the cancer and polyps developing before it, according to experts. An important first step here is colonoscopy, but the condition still demands a larger, more comprehensive prevention plan. Dr. Joel Levine, who co-founded the Colon Cancer Prevention Program of UConn Health, harped on the interaction of three broad areas in better understanding colon cancer. "The key is the interaction of three broad areas: insulin biology, inflammation biology, and the billions of species of bacteria in the colon, the microbiome,” he said in a UConn report. Insulin biology is anything that affects insulin levels, insulin-linked proteins, as well as insulin resistance. Such are risk factors collectively known as metabolic syndrome and cover risk factors such as obesity, diabetes, and a sedentary lifestyle. Cellular inflammation is an invisible process for the patient, and it often signals a bacterial shift in the colon. Plenty of inflammatory signaling, Levine explained, leads to damage to one’s genes, DNA, and other cellular elements. It could set the stage for more mutations, which could result in the development of colon polyps with their own specific history. Changes in one’s microbiome, composed of the billions of species in one’s gut and body, are linked to certain outcomes such as colon cancer. “Further evidence has demonstrated a relationship between specific bacteria and specific molecular pathways for colon polyps,” Levine added. Colonoscopy identifies most polyps, yet recognizes inflammation as well as bacterial changes can offer red flags before actual polyp formation. And while this detection tool is crucial, it is also deemed a must to lower a person’s risk profile in between colonoscopies. Levine said, for instance, that they have not seen a colon cancer case in patients they follow in their risk identification and reduction program in the last five years. This also takes into account the fact that under normal circumstances, there is up to a 10-year interval for polyps to form, so regular monitoring proves critical. Their center tracks molecular-level changes between colonoscopies via a form of the fecal immunochemical test, which is tasked to measure protein in blood in a stool sample in billionths of one gram. According to colorectal surgeon Dr. Jitesh Patel, colorectal cancer is around 90 percent treatable when discovered in the earliest stages. “While a colonoscopy may not be a fun experience, it could save your life,” he wrote in a commentary, highlighting this diagnostic tool is recommended for everyone starting age 50 or much younger if one is high-risk. Blacks, for one, should be screened at 45 years old or younger. The American Cancer Society noted that colorectal cancer emerges as the third leading cause of death related to cancer in the United States. But while it generally affects people in their 50s, a new report warned that colon and rectal cancers are on the rise among young adults. And the condition has “very, very subtle” signs and symptoms, earning it the title of being an invisible disease. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


News Article | April 25, 2017
Site: www.sciencedaily.com

You wouldn't think chili peppers and marijuana have much in common. But when eaten, both interact with the same receptor in our stomachs, according to a paper by UConn researchers published in the April 24 issue of the journal Proceedings of the National Academy of Sciences. The research could lead to new therapies for diabetes and colitis, and opens up intriguing questions about the relationship between the immune system, the gut and the brain. Touch a chili pepper to your mouth and you feel heat. And biochemically, you aren't wrong. The capsaicin chemical in the pepper binds to a receptor that triggers a nerve that fires off to your brain: hot! Those same receptors are found throughout the gastrointestinal tract, for reasons that have been mysterious. Curious, UConn researchers fed capsaicin to mice, and found the mice fed with the spice had less inflammation in their guts. The researchers actually cured mice with Type 1 diabetes by feeding them chili pepper. When they looked carefully at what was happening at a molecular level, the researchers saw that the capsaicin was binding to a receptor called TRPV1, which is found on specialized cells throughout the gastrointestinal tract. When capsaicin binds to it, TRPV1 causes cells to make anandamide. Anandamide is a compound chemically akin to the cannabinoids in marijuana. It was the anandamide that caused the immune system to calm down. And the researchers found they could get the same gut-calming results by feeding the mice anandamide directly. The brain also has receptors for anandamide. It's these receptors that react with the cannabinoids in marijuana to get people high. Scientists have long wondered why people even have receptors for cannabinoids in their brains. They don't seem to interact with vital bodily functions that way opiate receptors do, for example. "This allows you to imagine ways the immune system and the brain might talk to each other. They share a common language," says Pramod Srivastava, Professor of Immunology and Medicine at UConn Health School of Medicine. And one word of that common language is anandamide. Srivastava and his colleagues don't know how or why anandamide might relay messages between the immune system and the brain. But they have found out the details of how it heals the gut. The molecule reacts with both TRPV1 (to produce more anandamide) and another receptor to call in a type of macrophage, immune cells that subdue inflammation. The macrophage population and activity level increases when anandamide levels increase. The effects pervade the entire upper gut, including the esophagus, stomach and pancreas. They are still working with mice to see whether it also affects disorders in the bowels, such as colitis. And there are many other questions yet to be explored: what is the exact molecular pathway? Other receptors also react with anandamide; what do they do? How does ingesting weed affect the gut and the brain? It's difficult to get federal license to experiment on people with marijuana, but the legalization of pot in certain states means there's a different way to see if regular ingestion of cannabinoids affects gut inflammation in humans. "I'm hoping to work with the public health authority in Colorado to see if there has been an effect on the severity of colitis among regular users of edible weed," since pot became legal there in 2012, Srivastava says. If the epidemiological data shows a significant change, that would make a testable case that anandamide or other cannabinoids could be used as therapeutic drugs to treat certain disorders of the stomach, pancreas, intestines and colon. It seems a little ironic that both chili peppers and marijuana could make the gut chill out. But how useful if it's true.


News Article | April 25, 2017
Site: www.chromatographytechniques.com

You wouldn't think chili peppers and marijuana have much in common. But when eaten, both interact with the same receptor in our stomachs, according to a paper by UConn researchers published in the April 24 issue of the journal Proceedings of the National Academy of Sciences. The research could lead to new therapies for diabetes and colitis, and opens up intriguing questions about the relationship between the immune system, the gut and the brain. Touch a chili pepper to your mouth and you feel heat. And biochemically, you aren't wrong. The capsaicin chemical in the pepper binds to a receptor that triggers a nerve that fires off to your brain: hot! Those same receptors are found throughout the gastrointestinal tract, for reasons that have been mysterious. Curious, UConn researchers fed capsaicin to mice, and found the mice fed with the spice had less inflammation in their guts. The researchers actually cured mice with Type 1 diabetes by feeding them chili pepper. When they looked carefully at what was happening at a molecular level, the researchers saw that the capsaicin was binding to a receptor called TRPV1, which is found on specialized cells throughout the gastrointestinal tract. When capsaicin binds to it, TRPV1 causes cells to make anandamide. Anandamide is a compound chemically akin to the cannabinoids in marijuana. It was the anandamide that caused the immune system to calm down. And the researchers found they could get the same gut-calming results by feeding the mice anandamide directly. The brain also has receptors for anandamide. It's these receptors that react with the cannabinoids in marijuana to get people high. Scientists have long wondered why people even have receptors for cannabinoids in their brains. They don't seem to interact with vital bodily functions that way opiate receptors do, for example. "This allows you to imagine ways the immune system and the brain might talk to each other. They share a common language," says Pramod Srivastava, Professor of Immunology and Medicine at UConn Health School of Medicine. And one word of that common language is anandamide. Srivastava and his colleagues don't know how or why anandamide might relay messages between the immune system and the brain. But they have found out the details of how it heals the gut. The molecule reacts with both TRPV1 (to produce more anandamide) and another receptor to call in a type of macrophage, immune cells that subdue inflammation. The macrophage population and activity level increases when anandamide levels increase. The effects pervade the entire upper gut, including the esophagus, stomach and pancreas. They are still working with mice to see whether it also affects disorders in the bowels, such as colitis. And there are many other questions yet to be explored: what is the exact molecular pathway? Other receptors also react with anandamide; what do they do? How does ingesting weed affect the gut and the brain? It's difficult to get federal license to experiment on people with marijuana, but the legalization of pot in certain states means there's a different way to see if regular ingestion of cannabinoids affects gut inflammation in humans. "I'm hoping to work with the public health authority in Colorado to see if there has been an effect on the severity of colitis among regular users of edible weed," since pot became legal there in 2012, Srivastava says. If the epidemiological data shows a significant change, that would make a testable case that anandamide or other cannabinoids could be used as therapeutic drugs to treat certain disorders of the stomach, pancreas, intestines and colon.


News Article | April 4, 2017
Site: www.techtimes.com

A newly retired woman from Harwinton was looking for ways to get fit, so she got herself a Fitbit fitness device to help her track her daily steps and guide her toward her desired weight loss and health goals. Little did 73-year-old Patricia Lauder know that her Fitbit would actually do more than keep her fit: it will also save her life. Lauder recalled that for a number of weeks, she had not been feeling well. “[I] thought I might be battling a bad cold or walking pneumonia that I just couldn’t kick,” she said in a UConn Today report, adding that medical tests, X-rays, and other lab work actually came back negative for any health concern. She then began to felt fatigue as well as shortness of breath, where walking short distances proved to be a chore. Her Fitbit was also telling her an unusual story: her usual resting heart rate of 68 to 70 beats per minute increased by the day by five points. One day it just climbed to 140 bpm, she recalled. That was when Lauder phoned 911 and asked the ambulance to take her to UConn Health. At the emergency department, a CT scan revealed two large blood clots in her lung arteries. Called pulmonary embolisms, the clots were stressing her heart and lungs, as her lung artery pressure shot to 65 from the normal 25 and her heart was enlarged due to being overworked. According to Dr. JuYong Lee, who applied clot-busting medications directly into the clots via a catheter, the mortality rate of pulmonary embolisms is over 30 percent once it becomes massive. The clots can over-pressurize one’s heart and lead one’s blood pressure and oxygen level to significantly drop. Its largest risk factor: deep vein thrombosis, where a blood clot forms in a vein (often in one’s leg) and potentially travels up to the lungs. Lauder’s procedure was fortunately a minimally invasive one, and within a 24-hour post-operation, the clots disappeared and her heart and lung function resumed to normal. “I had the procedure on Friday, removed the catheter on Saturday and was home Monday evening,” the patient shared. Lauder credited her Fitbit for its life-saving role in this frightening event, saying she has no way of knowing her heart rate was getting riskily high if she didn’t have the device on her wrist. The doctor echoed her thoughts, calling the condition very critical and potentially leading to death without prompt medical attention. In early March, Tech Times reported that Fitbit has launched a new product called Fitbit Alta HR, an update to the previous Alta and touted to be the slimmest wrist-based device in the world and with a full-time heart rate sensor to boot. The renowned wearable gadget company made the watch thinner through reducing the chip’s size as well as the number of components. The smart watch is designed to be a quarter slimmer than the Fitbit Charge 2. Its innovation is a continuous, on-the-go heart rate tracking feature paired with PurePulse heart rate technology, which offers daylong heart tracking for important related health information. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


News Article | May 23, 2017
Site: www.marketwired.com

Johns Hopkins Genomics at The Johns Hopkins University, Georgia Cancer Center at Augusta University, CID Research, Progenity, Inc., DarwinHealth, Inc., and Channing Division of Network Medicine at Brigham and Women's Hospital Among New Qumulo Customers; Qumulo Reports More Than 2X Growth in Petabytes Shipped to Life Sciences and Medical Research Customers in 12 Months SEATTLE, WA--(Marketwired - May 23, 2017) - Qumulo, the leader in modern scale-out storage, today announced that leading life sciences and medical research institutions are choosing Qumulo to accelerate their data-intensive workflows, including cancer and infectious disease research, genomics, bioinformatics, proteomics, microscopy and big data. Johns Hopkins Genomics (including the NIH CIDR Program at The Johns Hopkins University), the Center for Infectious Disease Research, Georgia Cancer Center at Augusta University, Channing Division of Network Medicine at Brigham and Women's Hospital, Progenity, Inc., and DarwinHealth, Inc. have joined the rapidly growing number of customers turning to Qumulo to speed discovery of new medical breakthroughs. "Workflows in life sciences are characterized by massive volumes of machine-generated file data pipelined into downstream processes for analysis," said Peter Godman, co-founder and CTO of Qumulo. "The rapid growth of file-based storage and processing requirements compounded by limited IT resources has created a scalability crisis for life sciences and medical research organizations. Efficient, high-performance processing of file-based data is at the heart of innovation and discovery in life sciences -- something legacy file storage cannot provide. Qumulo has become the clear answer for data-intensive life sciences workflows." Qumulo accelerates data-intensive workflows in life science and medical research including cancer and infectious disease research and microscopy. Analysis of tissue and cancer tumor studies generates millions to billions of small files, and the expanding bio-repository file data requirements are outgrowing the capacity of legacy storage. Qumulo's modern scale-out storage provides researchers with faster analysis times and IT staff with real-time visibility and control at scale. The high performing, cost-effective storage platform allows for a single file system to be shared across groups to prevent long wait times previously associated with sharing large data sets among groups. Qumulo is the modern replacement for legacy scale-out storage architectures that cannot keep up with modern data requirements. Ron Hood, director of IT at the Center for Infectious Disease Research said, "Qumulo Core's modern architecture is built for the future and that's what closed the deal for us. We didn't want to spend our budget on legacy scale-out storage systems that are obsolete or will be in two to three years. Qumulo supports our needs today and well into the future, so that we can achieve faster times to analysis for our most critical research." Microscopy systems often generate image data sets as large as 1TB per experiment. Those images are stored and accessed for processing and analysis from client computers running operating systems such as Windows, macOS and Linux. The sequencing data is a widely varied collection of files ranging in size from a few kilobytes, often numbering in the millions to billions, up to large image files that can be 50 GB each. Qumulo is the ideal solution for this workload, providing high scalability, high performance, fast access to files across the entire range for processing and analysis, storage of billions of files and support for mixed file workloads. Qumulo Core was designed from the ground up for the new era of multi-petabyte data scale on premises and in the cloud. Qumulo Core stores tens of billions of files with scalable throughput and is the only product that provides real-time visibility and control for file systems at petabyte scale. Storage administrators and life sciences researchers can instantly see usage, activity and throughput at any level of the unified directory structure, no matter how many files in the file system, allowing them to pinpoint problems and effectively manage how storage is used by analysis pipelines. In addition, a Qumulo Core storage cluster can be installed and deployed in minutes without specialized IT expertise. Qumulo's publicly announced life sciences customers include: Carnegie Institution for Science, CID Research, Channing Division of Network Medicine at Brigham and Women's Hospital, DarwinHealth, Inc., Georgia Cancer Center at Augusta University, Institute for Health Metrics and Evaluation (IHME) at University of Washington, Johns Hopkins Genomics at The Johns Hopkins University, Progenity, Inc., UConn Health, University of Utah Scientific Computing and Imaging (SCI) Institute. Connect with Qumulo at Bio-IT World Qumulo will be featured in booth #333 at Bio-IT World, taking place May 23-25 in Boston. The company will sponsor, exhibit, and demonstrate the power of Qumulo Core for life sciences workflows. In addition, Peter Godman, the company's co-founder and CTO, will present on Kickstarting Breakthroughs in Life Sciences with Intelligent, Next-Generation Scale-Out Storage on Thursday, May 25 at 11:40am ET. To schedule one-on-one meetings with Qumulo representatives at Bio-IT World, send an email to info@qumulo.com or schedule online here. Suggested Tweet: Life Sciences and Medical Research Turning to @Qumulo For Modern Scale-Out File #Storage http://qumulo.com/4061 About Qumulo Qumulo enables enterprises to manage and store billions of digital assets with real-time visibility and control built directly into the file system. Going past the design limitations of legacy NAS, Qumulo Core is modern scale-out storage for the new era of multi-petabyte data footprints on premises and in the cloud. It is used by the leaders of data-intensive industries. Founded in 2012 by the inventors of scale-out NAS, Qumulo has attracted a world-class team of innovators, investors and partners. For more information, visit www.qumulo.com.


News Article | May 12, 2017
Site: www.eurekalert.org

Get up and move! UConn study finds any exercise is good exercise when it comes to boosting your mood You don't have to spend hours at the gym or work up a dripping sweat to improve your mood and feel better about yourself, researchers at the University of Connecticut say in a new study. If you lead a sedentary lifestyle -- spending large parts of your day sitting at home or at work - simply getting out of your chair and moving around can reduce depression and lift your spirits. "We hope this research helps people realize the important public health message that simply going from doing no physical activity to performing some physical activity can improve their subjective well-being," says Gregory Panza, a graduate student in UConn's Department of Kinesiology and the study's lead author. "What is even more promising for the physically inactive person is that they do not need to exercise vigorously to see these improvements," Panza continues. "Instead, our results indicate you will get the best 'bang for your buck' with light or moderate intensity physical activity." For those keeping score, light physical activity is the equivalent of taking a leisurely walk around the mall with no noticeable increase in breathing, heart rate, or sweating, says Distinguished Kinesiology Professor Linda Pescatello, senior researcher on the project. Moderate intensity activity is equivalent to walking a 15-20-minute mile with an increase in breathing, heart rate, and sweating, yet still being able to carry on a conversation. Vigorous activity is equivalent to a very brisk walk or jogging a 13-minute mile with a very noticeable increase in breathing, heart rate, and sweating to the point of being unable to maintain a conversation. The study looked at 419 generally healthy middle-aged adults who wore accelerometers on their hips to track physical activity over four days. Participants also completed a series of questionnaires asking them to describe their daily exercise habits, psychological well-being, depression level, pain severity, and extent to which pain interfered with their daily activities. The last finding is actually good news for folks who enjoy hard, calorie-burning workouts, as it doesn't support a widely reported recent study that found high intensity workouts significantly lowered some people's sense of well-being. "Recent studies had suggested a slightly unsettling link between vigorous activity and subjective well-being," says Beth Taylor, associate professor of kinesiology and another member of the research team. "We did not find this in the current study, which is reassuring to individuals who enjoy vigorous activity and may be worried about negative effects." Many previous studies have attempted to identify the best exercise regimen to improve people's sense of well-being. Yet no clear consensus has emerged. Some studies say moderate or vigorous activity is best. Others say low intensity exercise is better. The differences, the UConn researchers say, may be due to the way the studies were designed and possible limitations in how people's well-being and levels of physical activity were measured. The UConn study is believed to be the first of its kind to use both objective (accelerometers) and subjective (questionnaires) measurements within a single group to examine the relationship between physical activity intensity and well-being. Yet the UConn research also has its limits, Panza says. All of the individuals who participated in the UConn study had a generally positive sense of well-being going into the project and were generally physically active. So their answers in the questionnaires need to be framed in that context. Whether the same results would hold true for people with lower subjective well-being or lower levels of physical activity is unknown, Panza says. Also, the conclusions formed in the UConn study are based on information gathered at a single point in time. A longitudinal study that tracks people's feelings and physical activity over time would go a long way toward helping determine what exercise regimen might be best for different populations, Panza said. "If it doesn't make us feel good, we don't want to do it," says Taylor. "Establishing the link between different types, doses, and intensities of physical activity on well-being is a very important step in encouraging more people to exercise." The study was published in the Journal of Health Psychology in February.


News Article | May 9, 2017
Site: www.chromatographytechniques.com

Certain blood vessels in the brainstem constrict when blood vessels elsewhere in the body would dilate. And that contrary behavior is what keeps us breathing, according to a new paper by UConn researchers published May 8 in eLife. If the body were a marching band, the brainstem would be the drum major. It keeps our heart beating and our lungs breathing in the essential rhythms of life. And just like a drum major, the job is more complex than it looks. If cellular waste products build up in the body, the brainstem has to jolt the lungs into action without disrupting other bodily functions, as surely as a drum major reins in a wayward woodwind section without losing the low brass. Neuroscientists studying the brainstem have focused on neurons, which are brain cells that send signals to one another and all over the body. But focusing just on the neurons in the brainstem is like staring only at the drum major's hands. Recently, neuroscientists have come to understand that astrocytes, cells once thought to simply provide structure to the brain, also release signaling molecules that regulate neurons' function. But until now, no one even considered the possibility that blood vessels may be similarly specialized. For more than a century, doctors and scientists have known that blood vessels dilate when cellular waste products like carbon dioxide build up. Widening the vessels allows fresh blood to flush through, carrying in oxygen and washing away the acidic carbon dioxide. This has been shown to be true throughout the body, and is standard dogma in undergraduate physiology classes. UConn physiologist Dan Mulkey was teaching exactly that to undergraduates one day when he realized that it couldn't possibly be true in a certain part of the brainstem. "I thought, wow. If that happened in the region of the brain I study, it would be counterproductive," Mulkey says. He studies the retrotrapezoid nucleus (RTN), a small region in the brainstem that controls breathing. He's shown in the past that RTN neurons respond to rising levels of carbon dioxide in the bloodstream by stimulating the lungs to breathe. But if the blood vessels in the RTN dilated in response to rising carbon dioxide the same way blood vessels do everywhere else, it would wash out that all-important signal, preventing cells in the RTN from doing their job driving us to breathe. It would be as if the drum major didn't notice the percussion section wandering off to left field. When Mulkey returned to the lab, he asked his team, including NIH postdoctoral fellow Virginia Hawkins, to see how blood vessels in thin slices of brainstem respond to carbon dioxide. And they saw it was indeed true - RTN blood vessels constricted when carbon dioxide levels rose. But blood vessels from slices of cortex (the wrinkled top part of the brain) dilated in response to high carbon dioxide, just like the rest of the body. But how did the blood vessels know to act differently in the RTN? Mulkey guessed that RTN astrocytes had something to do with it. He suspected that the astrocytes were releasing adenosine triphosphate (ATP), a small molecule cells can use to signal one another. And that was causing the RTN blood vessels to constrict. When they tested it, they found the hypothesis was correct. The astrocytes in the RTN were behaving differently than astrocytes anywhere else in the body. When these brainstem astrocytes detected high levels of carbon dioxide, they released ATP signaling to the neurons and blood vessels. When the researchers induced the astrocytes artificially to release ATP, they got the same results. Bathing the RTN blood vessels directly in ATP also caused them to constrict. Blocking ATP receptors blocked the ability of blood vessels to respond to carbon dioxide. When the team did the same experiments in live animals, they got the same results. Perhaps most importantly, manipulating blood vessels in the RTN actually influenced how animals breathe, thus linking regulation of blood vessel diameter to behavior. The majority of this research was done by UConn undergraduates, including Ashley Trinh, Colin Cleary, and Todd Dubreuil, as well as Elliot Rodriguez, a summer student in the National Science Foundation (NSF) Research Experience for Undergraduates in Physiology and Neurobiology program at UConn, who studies at Gettysburg College in Pennsylvania the rest of the year. The students' work uncovered a major discovery in neurophysiology. The work was funded in part by grants from the National Institutes of Health (HL104101 HL126381) and the Connecticut Department of Public Health (150263). "This is a big change in how we think about breathing," Mulkey says. And about blood vessels. Even in a single organ like the brain, the purpose of blood flow is not the same everywhere. Tailored responses in the RTN keep the body's drum major conducting, and let the band play on.


News Article | May 9, 2017
Site: www.eurekalert.org

Certain blood vessels in the brainstem constrict when blood vessels elsewhere in the body would dilate. And that contrary behavior is what keeps us breathing, according to a new paper by UConn researchers published May 8 in eLife. If the body were a marching band, the brainstem would be the drum major. It keeps our heart beating and our lungs breathing in the essential rhythms of life. And just like a drum major, the job is more complex than it looks. If cellular waste products build up in the body, the brainstem has to jolt the lungs into action without disrupting other bodily functions, as surely as a drum major reins in a wayward woodwind section without losing the low brass. Neuroscientists studying the brainstem have focused on neurons, which are brain cells that send signals to one another and all over the body. But focusing just on the neurons in the brainstem is like staring only at the drum major's hands. Recently, neuroscientists have come to understand that astrocytes, cells once thought to simply provide structure to the brain, also release signaling molecules that regulate neurons' function. But until now, no one even considered the possibility that blood vessels may be similarly specialized. For more than a century, doctors and scientists have known that blood vessels dilate when cellular waste products like carbon dioxide build up. Widening the vessels allows fresh blood to flush through, carrying in oxygen and washing away the acidic carbon dioxide. This has been shown to be true throughout the body, and is standard dogma in undergraduate physiology classes. UConn physiologist Dan Mulkey was teaching exactly that to undergraduates one day when he realized that it couldn't possibly be true in a certain part of the brainstem. "I thought, wow. If that happened in the region of the brain I study, it would be counterproductive," Mulkey says. He studies the retrotrapezoid nucleus (RTN), a small region in the brainstem that controls breathing. He's shown in the past that RTN neurons respond to rising levels of carbon dioxide in the bloodstream by stimulating the lungs to breathe. But if the blood vessels in the RTN dilated in response to rising carbon dioxide the same way blood vessels do everywhere else, it would wash out that all-important signal, preventing cells in the RTN from doing their job driving us to breathe. It would be as if the drum major didn't notice the percussion section wandering off to left field. When Mulkey returned to the lab, he asked his team, including NIH postdoctoral fellow Virginia Hawkins, to see how blood vessels in thin slices of brainstem respond to carbon dioxide. And they saw it was indeed true - RTN blood vessels constricted when carbon dioxide levels rose. But blood vessels from slices of cortex (the wrinkled top part of the brain) dilated in response to high carbon dioxide, just like the rest of the body. But how did the blood vessels know to act differently in the RTN? Mulkey guessed that RTN astrocytes had something to do with it. He suspected that the astrocytes were releasing adenosine triphosphate (ATP), a small molecule cells can use to signal one another. And that was causing the RTN blood vessels to constrict. When they tested it, they found the hypothesis was correct. The astrocytes in the RTN were behaving differently than astrocytes anywhere else in the body. When these brainstem astrocytes detected high levels of carbon dioxide, they released ATP signaling to the neurons and blood vessels. When the researchers induced the astrocytes artificially to release ATP, they got the same results. Bathing the RTN blood vessels directly in ATP also caused them to constrict. Blocking ATP receptors blocked the ability of blood vessels to respond to carbon dioxide. When the team did the same experiments in live animals, they got the same results. Perhaps most importantly, manipulating blood vessels in the RTN actually influenced how animals breathe, thus linking regulation of blood vessel diameter to behavior. The majority of this research was done by UConn undergraduates, including Ashley Trinh, Colin Cleary, and Todd Dubreuil, as well as Elliot Rodriguez, a summer student in the National Science Foundation (NSF) Research Experience for Undergraduates in Physiology and Neurobiology program at UConn, who studies at Gettysburg College in Pennsylvania the rest of the year. The students' work uncovered a major discovery in neurophysiology. The work was funded in part by grants from the National Institutes of Health (HL104101 HL126381) and the Connecticut Department of Public Health (150263). "This is a big change in how we think about breathing," Mulkey says. And about blood vessels. Even in a single organ like the brain, the purpose of blood flow is not the same everywhere. Tailored responses in the RTN keep the body's drum major conducting, and let the band play on.


News Article | May 9, 2017
Site: www.chromatographytechniques.com

Certain blood vessels in the brainstem constrict when blood vessels elsewhere in the body would dilate. And that contrary behavior is what keeps us breathing, according to a new paper by UConn researchers published May 8 in eLife. If the body were a marching band, the brainstem would be the drum major. It keeps our heart beating and our lungs breathing in the essential rhythms of life. And just like a drum major, the job is more complex than it looks. If cellular waste products build up in the body, the brainstem has to jolt the lungs into action without disrupting other bodily functions, as surely as a drum major reins in a wayward woodwind section without losing the low brass. Neuroscientists studying the brainstem have focused on neurons, which are brain cells that send signals to one another and all over the body. But focusing just on the neurons in the brainstem is like staring only at the drum major's hands. Recently, neuroscientists have come to understand that astrocytes, cells once thought to simply provide structure to the brain, also release signaling molecules that regulate neurons' function. But until now, no one even considered the possibility that blood vessels may be similarly specialized. For more than a century, doctors and scientists have known that blood vessels dilate when cellular waste products like carbon dioxide build up. Widening the vessels allows fresh blood to flush through, carrying in oxygen and washing away the acidic carbon dioxide. This has been shown to be true throughout the body, and is standard dogma in undergraduate physiology classes. UConn physiologist Dan Mulkey was teaching exactly that to undergraduates one day when he realized that it couldn't possibly be true in a certain part of the brainstem. "I thought, wow. If that happened in the region of the brain I study, it would be counterproductive," Mulkey says. He studies the retrotrapezoid nucleus (RTN), a small region in the brainstem that controls breathing. He's shown in the past that RTN neurons respond to rising levels of carbon dioxide in the bloodstream by stimulating the lungs to breathe. But if the blood vessels in the RTN dilated in response to rising carbon dioxide the same way blood vessels do everywhere else, it would wash out that all-important signal, preventing cells in the RTN from doing their job driving us to breathe. It would be as if the drum major didn't notice the percussion section wandering off to left field. When Mulkey returned to the lab, he asked his team, including NIH postdoctoral fellow Virginia Hawkins, to see how blood vessels in thin slices of brainstem respond to carbon dioxide. And they saw it was indeed true - RTN blood vessels constricted when carbon dioxide levels rose. But blood vessels from slices of cortex (the wrinkled top part of the brain) dilated in response to high carbon dioxide, just like the rest of the body. But how did the blood vessels know to act differently in the RTN? Mulkey guessed that RTN astrocytes had something to do with it. He suspected that the astrocytes were releasing adenosine triphosphate (ATP), a small molecule cells can use to signal one another. And that was causing the RTN blood vessels to constrict. When they tested it, they found the hypothesis was correct. The astrocytes in the RTN were behaving differently than astrocytes anywhere else in the body. When these brainstem astrocytes detected high levels of carbon dioxide, they released ATP signaling to the neurons and blood vessels. When the researchers induced the astrocytes artificially to release ATP, they got the same results. Bathing the RTN blood vessels directly in ATP also caused them to constrict. Blocking ATP receptors blocked the ability of blood vessels to respond to carbon dioxide. When the team did the same experiments in live animals, they got the same results. Perhaps most importantly, manipulating blood vessels in the RTN actually influenced how animals breathe, thus linking regulation of blood vessel diameter to behavior. The majority of this research was done by UConn undergraduates, including Ashley Trinh, Colin Cleary, and Todd Dubreuil, as well as Elliot Rodriguez, a summer student in the National Science Foundation (NSF) Research Experience for Undergraduates in Physiology and Neurobiology program at UConn, who studies at Gettysburg College in Pennsylvania the rest of the year. The students' work uncovered a major discovery in neurophysiology. The work was funded in part by grants from the National Institutes of Health (HL104101 HL126381) and the Connecticut Department of Public Health (150263). "This is a big change in how we think about breathing," Mulkey says. And about blood vessels. Even in a single organ like the brain, the purpose of blood flow is not the same everywhere. Tailored responses in the RTN keep the body's drum major conducting, and let the band play on.

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