Axcella Announces Positive Interim Findings from Ongoing Clinical Study of AXA1125/AXA1957 in Subjects with NAFLD and Expected 2020 Milestones -…

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Axcella (Nasdaq: AXLA), a clinical-stage biotechnology company focused on leveraging endogenous metabolic modulators (EMMs) to pioneer a new approach for treating complex diseases and improving health, today provided an update from its ongoing clinical study in adult subjects with non-alcoholic fatty liver disease (NAFLD) and announced its anticipated milestones for 2020.

Interim Analysis of Ongoing Clinical Study of AXA1125/AXA1957 (AXA1125-003)

Axcella has completed the enrollment of 102 adult subjects with NAFLD in an ongoing randomized, dose-ranging study in which subjects receive either AXA1125, one of two AXA1957 doses or placebo for 16 weeks. This study, which is being conducted at 18 U.S. medical centers, is assessing the impact of AXA1125/AXA1957 on safety, tolerability and physiology, as measured by a comprehensive panel of imaging and soluble biomarkers related to metabolism, inflammation and fibrosis.

An interim analysis has been conducted that includes data from approximately half of the study population through the full 16 weeks of administration. The analysis shows that AXA1125 and both doses of AXA1957 have been safe and well tolerated to date. Additionally, both AXA1125 and AXA1957 demonstrated clinically relevant responses on the three biological nodes fundamental to liver health and disease: metabolism (MRI-PDFF and HOMA-IR), inflammation (ALT, CK-18, cT1) and fibrogenesis (proC3). The onset of response in some biomarkers was seen as early as the eight-week, post-baseline assessment with continued improvement through 16 weeks.

These interim non-invasive data indicate that AXA1125 and AXA1957 are having a positive impact on multiple dysregulated biological pathways related to health and disease that are common in NAFLD/NASH patients, said Stephen A. Harrison, M.D., the principal investigator (PI) of the study, medical director of Pinnacle Clinical Research in San Antonio, TX, and visiting professor of Hepatology at the University of Oxford, UK. These are particularly encouraging early findings, providing hope that a multifactorial effect can be generated from novel compositions of endogenous metabolic modulators.

These findings will be included in the companys presentation at the J.P. Morgan Healthcare Conference next week. Details regarding this presentation will be provided in a separate press release.

We are pleased with the swift pace of enrollment and the data generated to date in our sizable clinical study of AXA1125 and AXA1957. The interim analysis increases our confidence in the potential for these candidates to become foundational therapeutics for NASH patients, said Bill Hinshaw, President and CEO of Axcella. Our excitement continues to build as we begin a major year for the company, with five planned clinical readouts and the initiation of our first planned Phase 2b/3 clinical trial in 2020.

2020 Milestones

Liver Product Candidates

Blood Product Candidate

About Endogenous Metabolic Modulators (EMMs)

EMMs are a broad family of molecules, including amino acids, that regulate human metabolism. Axcella is developing a range of novel product candidates that are comprised of multiple EMMs engineered in distinct combinations and ratios to simultaneously impact multiple metabolic pathways to modify the root causes of various complex diseases and improve health.

About Axcellas Ongoing Clinical Studies

Each of the companys ongoing clinical studies are being conducted as non-investigational new drug (IND) application clinical studies under U.S. Food and Drug Administration regulations and guidance supporting research with food. These studies evaluate product candidates for safety, tolerability and effects on the normal structures and functions in humans, including in individuals with disease. They are not designed or intended to evaluate a product candidates ability to diagnose, cure, mitigate, treat or prevent a disease. If Axcella decides to further develop a product candidate as a potential therapeutic, as is the case with AXA1665 and AXA1125/1957, subsequent studies will be conducted under an IND.

Internet Posting of Information

Axcella uses its website, http://www.axcellahealth.com, as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Such disclosures will be included on the companys website in the Investors and News section. Accordingly, investors should monitor such portions of the companys website, in addition to following its press releases, SEC filings and public conference calls and webcasts.

About Axcella

Axcella is a clinical-stage biotechnology company focused on leveraging endogenous metabolic modulators (EMMs) to pioneer a new approach for treating complex diseases and improving health. The companys product candidates are comprised of EMMs that are engineered in distinct combinations and ratios to simultaneously impact multiple biological pathways. Axcellas pipeline includes lead therapeutic candidates for overt hepatic encephalopathy (OHE) and non-alcoholic steatohepatitis (NASH). Additional muscle- and blood-related programs are in earlier-stage development. For more information, please visit http://www.axcellahealth.com.

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the development potential of the companys product candidates, including AXA1665, AXA1125 and AXA1957, potential expansion into new therapeutic fields, the ability of endogenous metabolic modulators to impact dysregulated metabolism and health and the timing of the companys clinical studies and trials and the timing of receipt of data from the same. The words may, will, could, would, should, expect, plan, anticipate, intend, believe, estimate, predict, project, potential, continue, target and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on managements current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those related to the breadth and potential uses of the companys pipeline of product candidates, the potential of AXA1125 and AXA1957 to become foundational therapies, interim and topline data readouts and timing of the same, the planned timing of an IND filing for AXA1665, the strength of the AXA Development Platform, the efficiency of the companys discovery and development approach, the clinical development and safety profile of the companys product candidates and their health or therapeutic potential, whether and when, if at all, the companys product candidates will receive approval from the U.S. Food and Drug Administration, or other comparable regulatory authorities, and for which, if any, indications, competition from other biotechnology companies, the companys liquidity, its ability to successfully develop product candidates through current and future milestones on the anticipated timeline, if at all, past results from non-IND clinical studies not being representative of future results, and other risks identified in the companys SEC filings, including Axcellas Quarterly Report on Form 10-Q and subsequent filings with the SEC. The company cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. Axcella disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent the companys views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. The company explicitly disclaims any obligation to update any forward-looking statements.

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Axcella Announces Positive Interim Findings from Ongoing Clinical Study of AXA1125/AXA1957 in Subjects with NAFLD and Expected 2020 Milestones -...

Study Refutes Findings that Acidification Affects Fish Behavior – The Scientist

New experimental results refute a decade of research suggesting that increased ocean acidificationthe process by which increasingly available atmospheric carbon dioxide is absorbed by the ocean, lowering its pHalters the behavior of coral reef fish, researchers reported today in Nature. The researchers saw no significant difference in the animals behavior in several different laboratory-based tests in water with varying pH.

Many studies published over the last 10 years reported that when the pH of seawater in the lab goes down to levels that match future predictions, coral reef fish behave differently. Specifically, rather than avoid areas where chemical signals indicate a predators presence, the fish would gravitate toward these areas. Acidification also changes their activity levels and their preference for turning right or left to avoid an obstacle in their path.

The initial results being published in this field were incredible from a biological perspective. The magnitude of the effect of ocean acidification (elevated CO2) on fish behaviour was huge, Timothy Clark, a biologist at Deakin University and the lead author of the latest study, tells The Scientist in an email. Yet there had been no attempt by independent research groups to replicate these profound findings.

Co-author Josephine Sundin looks into an exposure tan on Lizard Island in Australia in 2014.

tim clark

So the team set out to replicate the findings and possibly investigate their physiological bases using more than 900 individual fish from six species over three years. The fish, which came from the northern portion of the Great Barrier Reef or an Australian aquarium, were acclimated to different levels of acidification for four days or more and then exposed to a behavioral cuesuch as an obstacle to swim around or chemicals that signal that a predator is near.

The scientists didnt record any substantial differences in the ways the fish responded to their environments based on altered pH and concluded that ocean acidification has negligible effects on the behavior of coral reef fish.

As a part of this project, the scientists published standardized methods for studying how fish respond to chemical cues in 2017. They say one of the main challenges of conducting the new experiments was a lack of consistent and effective methodology reported by previous groups. In an effort to emphasize transparency, the team filmed all of their behavioral observations.

Replications are extremely important for the scientific process because they can unearth errors to help science progress down the correct path, says Fredrik Jutfelt, a biologist at the Norwegian University of Science and Biology and an author of the study. He says his team hopes that the results will demonstrate that value to scientists and funding agencies. But Danielle Dixson, a biologist at the University of Delaware who worked on some of those previous studies, including one about predator cues, calls a comparison between the new study and prior research inappropriate, based on a number of methodological differences.

It is not surprising that the experimental findings from Clark et al. differ from those we collected in the past, as a number of methodological changes were made, says Dixson, explaining in an email that Clarks team used fish at different life stages collected from different environments than those in previous studies. Replication of science is important, and the findings of our early ocean acidification studies have been confirmed independently in other systems, both temperate and tropical, by other laboratory groups, testing a number of different species, both invertebrate and vertebrate.

Tim Clark (left) and Fredrik Jutfelt (right) collecting fish near Lizard Island inAustralia in 2014

josephine sundin

Given their results, Clark and his team are confident that acidification doesnt affect coral reef fish behavior and do not plan to continue researching the question. Nevertheless, if any readers are not convinced by our study then we would welcome collaborations so that other scientists can see the same results with their own eyes, says Clark. We believe that there are much greater threats facing coral reef fish, such as ocean warming, habitat destruction and pollution, and thus these factors deserve more of our research attention with a goal to conserve coral reefs and all the wildlife they support.

Rachael Heuer, a postdoc studying acidification and fish physiology at the University of Miami, who has done recent work showing physiological and behavioral changes in fish in high-acid environments, says, the conclusion that CO2 does not impact behavior in coral reef fishes is overextended and fails to provide a full picture of the field. She emphasizes that behavioral effects of acidification have been reported by several research groups. There is undoubtedly variation in behavioral responses to CO2, but I dont believe these differences can be entirely attributed to methodology.

T. Clark et al., Ocean acidification does not impair the behaviour of coral reef fishes,Nature, doi:10.1038/s41586-019-1903-y, 2020.

Emma Yasinski is a Florida-based freelance reporter. Follow her on Twitter@EmmaYas24.

Editors note (January 8): The images of the authors were added after the story was originally published.

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Study Refutes Findings that Acidification Affects Fish Behavior - The Scientist

Meet The Deep-Diving, Ear-Splitting 4,500-Pound Rock Star of Ao Nuevo – – Bay Nature

Male elephant seals are among the loudest mammals ever recorded, and they can weigh more than two tons. (Photo by Steve Zamek, Feather Light Photography)

On a sparkling blue January morning, I meet marine biologist Patrick Robinson, who will escort me around Ao Nuevo State Park, a patch of dunes and bluffs an hours drive south of San Francisco. As we start along a sandy path toward the beach, he explains that his role is not only to protect me from the thousands of elephant seals currently camped out here, but to protect the elephant seals from me. That sounds sensible enoughuntil we come over a rise and I see what they actually look like in the flesh.

Blocking the path is a massive blob of quivering blubber, braying like a donkey. This hunk of chonk, the size and shape of Jabba the Hutt, is a male northern elephant seal. He might weigh as much as 4,500 pounds, and he can flop his jiggly body across the sand as fast as we can run. Robinson warns me to watch where I walk, and to be careful not to invade any seals personal space. I make eye contact with Jabba, who watches us with mild curiosity, his dark eyes lustrous over the dangling snoot that gives the species its name. I am not even slightly tempted to get closer.

A few hundred yards more down the path there are seals everywhere, lolling and scratching. We weave among them, trying not to get too close. But every rounded dune comes alive as a seal back or flank; what looks like driftwood sighs deeply and twitches a flipper. There are just so many of them. Like clockwork every winter, more than 2,000 adults congregate on these shores for their annual sealapalooza of fighting, birthing, nursing, matingall of lifes main events in just a few months. Sort of like Jersey Shore, but for seals.

When they come together in space and time, everything is very extreme. The level of competition is extreme, the level of risk is extreme. These animals are fasting, with no food and water, so the physiological constraints are extreme.

While the males battle for breeding rights and the females nurse their newborn pups, none of the adults eat or drink, losing more than 30 percent of their body weight. This ultra-endurance event is just one of the many extraordinary things elephant seals do. When they come together in space and time, everything is very extreme, says behavioral ecologist Colleen Reichmuth of the Institute of Marine Sciences at University of California Santa Cruz. The level of competition is extreme, the level of risk is extreme. These animals are fasting, with no food and water, so the physiological constraints are extreme.

Because it is both amazing and convenient to study, the northern elephant seal, which ranges throughout the North Pacific, is one of the best-measured of all marine mammals. Over the years, using harnesses and marine glue, straps and cattle-ear-tag guns, scientists have attached all sorts of gizmos to the creatures mighty heads and shoulderscameras, GPS tags, depth sensors, heartbeat monitorsto measure where theyre going and what theyre doing way out there in the ocean. Every time we turned around, wed uncover some really cool fact or observation, says UCSC evolutionary biologist Daniel Costa, who first began studying these mammals in the mid-70s and now supervises all Ao Nuevo elephant seal research. Scientists here and elsewhere learned that elephant seals dive deeper (nearly 6,000 feet), swim farther (averaging more than 9,000 miles a year), and hold their breath longer (up to two hours) than any other seal. Only their cousins, the southern elephant seals, can hold their breath for as long as they canup to two hours. (Harbor seals, by comparison, can hold their breath just a half hour and go no deeper than 1,500 feet.) Males are more than three times the size of females, one of the biggest sex-based size differences among mammals. They arent just polygamous, but maybe the most polygamous of mammals, forming harems in which one male might mate with up to 100 females.

The extraordinary nature of this animal has already forced scientists to question the supposed limits of mammal physiology. These deep-diving, breath-holding, long-fasting creatures are closely related to other marine mammals that cant pull off such feats. The implication is that minor tweaks to mammal biology can translate to huge differences in ability. Elephant seals may even teach us how our own bodies function and what we might be capable of. For now, though, the question that preoccupies the scientists of Ao Nuevo is what will happen to the animals in a warming world. Climate change is poised to disrupt everything in the ocean in coming decades, from ocean currents to the location of the most and best fish. A new wave of research projects here probe whether these unusual mammals are resilient enough to keep thrivingwhether they will be extraordinary enough to cope with the huge changes heading their way.

The sands of Ao Nuevo were not always jammed with dozing seals. In the late 1880s, the northern elephant seal was thought to be extinct, decimated by blubber-hunters, until some naturalists found a tiny band of holdouts on an island off Mexicoand promptly killed most of them to take them home as specimens.

But elephant seals are nothing if not gritty, and a few survivors held on, slowly rebuilding their numbers. By the 1970s the seals began pupping and breeding at Ao Nuevo, just 30 minutes drive north of UC Santa Cruz and its world-class marine biology department. That proximity was a lucky stroke for researchers: The animals tolerate the humans who tiptoe amongst them. And as biological outliers, they offer a singular chance to study the outer fringes of mammalian performance.

The portly creatures that Robinson and I sneak past dont look like stupendous athletes. Yet for up to eight months of the year, they roam the remote eastern and central North Pacific, plunging way below the surface on nearly continuous foraging dives. Blubber analysis conducted by Chandra Goetsch in Costas lab indicates they eat deepwater prey like lanternfish, squid, and viperfish, and they eat a lot of it. In roughly seven months of migration, female seals gain an average of nearly 600 pounds, which can mean they nearly double their body weight.

As they dive, their hearts slow to below five beats a minute while blood flow to the muscles shuts offa trick that interests anesthesiologists who would like to stop circulation to a body part during surgery, then restart the flow without damage. Elephant seals can also surface from marathon dives to breathe for less than five minutes, then dive again. Theres a lot we dont understand about how they do that, says behavioral ecologist Birgitte McDonald of Moss Landing Marine Laboratories. The behavior seems to break physiological rules: If a Weddell seal, for instance, dives for more than 20 minutes, it uses up all its oxygen. Its muscles start dumping lactate into its blood, and the seal must breathe for 90 minutes or more before diving again.

The fact that these seals wander so widely, dive so deep, and reliably return to Ao Nuevo means they can also be employed as sensors to probe parts of the ocean that are difficult or expensive to measure. One student in Costas lab recently explored using data gathered by fluorescence meters attached to the seals to cheaply chart chlorophyll levels out in the North Pacific, measuring that all-important first link of the food chainthe phytoplankton and algae that ultimately feed everything else in the ocean, from baby fish to blue whales, and which indirectly reflect how windy or warm ocean conditions are.

Robinson and I reach our first destination: an observation deck overlooking Bight Beach, where roughly 75 northern elephant seals sprawl in the sun, females honking and rasping, their chocolate-brown pups beside them mewling and trilling. Theres just one enormous male down near the water, keeping watch. It looks like a day spa with a really scary bouncer.

In three-quarters of confrontations one of the males backs down before things get violent. In a species famed for aggression, theres actually way more talk than action.

He looks tense, for good reason. The privilege of breeding is reserved for just a few dominant males like him; 99 percent of elephant seal males never mate. This guy vanquished the competition, but the also-rans just wont stop trying. Elephant seal combat can be brutal: the bulls square off, rear up, then smash their chests together, rassling and shoving and gashing at one anothers shoulders and flanks with their teeth, leaving each other raw and bloody.

Even now, a male with a big glob of dried blood on his shoulder lurks at the top of the cove. Chances are, Scary Bouncer Seal caught him trying to get with his ladies and taught him a lesson. But although it is spectacular, bull vs. bull is rare, because it is just too draining. Reichmuth and her former graduate student Caroline Casey discovered a few years ago that the big brutes prefer to roar at each other rather than waste their energy on physical attack.

Here at this beach, the variety of sounds is indescribable, although I try: Asthmatic lion, I scribble in my notebook. Old outboard motor. Gargling drain. Strangling a Pomeranian. Above it all rises the long, throbbing snort-roar of that big guy near the water. (Bonus elephant seal freak fact: They are among the loudest of any land mammal.)

To understand what those calls mean and how they relate to breeding success, Reichmuth and Casey first mapped the bull hierarchy. They filmed confrontations between tagged males, recording the outcome of each standoff or fight. Because not all bulls fight one another directly, and because she couldnt track every last conflict, Casey used a method borrowed from competitive chess called the Elo system to assign each bull a comparative rank.

Next, they recorded each males voice and did playback experiments. The seals evidently understood the bellows: Middle-status males charged toward the speaker when they heard recorded calls of low-ranking bulls, but those same mid-rank guys fled from sounds made by alpha males. We were like, What is going on here? What are they saying to each other? Casey says. We wanted to decode the language of male elephant seals.

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Top males did not have lower voices or longer calls or share any other obvious characteristic. What Caseys analysis showed instead is that each males voice is distinctive and stays the same from year to year. The kicker: When she drove up to Point Reyes National Seashore and played her Ao Nuevo recordings to the elephant seal colony there, the bulls didnt react either way.

Her interpretation is the bulls recognize the voices of bulls theyve met and keep a mental ledger of whom theyve fought and who won, so as to avoid unnecessary and exhausting rematches. Its amazing, she says. It means that they have really good memory, and are able to manage and remember a lot of unique calls. Its also an effective conflict-avoidance strategy: in three-quarters of confrontations, she found, one of the males backs down before things get violent. In a species famed for aggression, theres actually way more talk than action.

While the bulls bluster and brawl, elephant seal females endure their own physiological marathon. Without eating or drinking, a mother produces nine pounds of milk per day during the roughly four weeks she nurses her pup. The rich milk fattens the pup, preparing it to survive alone on the beach for months after the mother returns to the sea.

Mother seals draw on their own fat reserves to do this, so its essential they arrive here at a healthy weight. The researchers at Ao Nuevo are careful not to disturb the animals too often or for too long, particularly mother-pup pairs. So to track their health, Robinson is developing creative ways to weigh them without disturbing them, such as using drones that estimate their size with photography. Today were hoping to weigh seal #9454, one of two dozen females who has been carrying a satellite tag that tracked her path through the Pacific. Robinson plans to link her route to her weight for a multidimensional view of where and how well she ate.

We spot her among a dozen other mothers, her chin propped on her plump days-old pup. The small satellite device epoxyed to her head gives her an aristocratic, eccentric look, like a drunken duchess at a garden party. As Robinsons drone hums above her, snapping pictures, she regally ignores it.

Weighing her unobtrusively is important because her reproductive success requires her to conserve her energy. All mothers move around, jockeying for space on the beach and warding off intrusive males. But much of a mothers energy goes into milk. When pups are first born, McDonald found, mothers produce milk thats 20 percent fat, skyrocketing to nearly 60 percent right before weaning. (By comparison, cows milk is only about 4 percent fat.) Despite the physical toll of producing milk while also fasting, elephant seal mothers will sometimes nurse both their own pup and an orphaned onean effort doomed to fail. To nurse a pup thats not your own, thats really difficult to explain, given what we know about elephant seals, says Reichmuths postdoctoral student Juliette Linossier.

One possibility is that the mothers just dont notice the difference. But that doesnt seem to be the case, Linossier has found. She shows me a video from last winter, in which she plays a recording of calls made by a random stranger pup to a seal mother, who barely reacts. But in response to a recording of sounds from her own pup, the mother snaps her head up and whips around to stare at the source. She flops a foot or two toward the speaker, clucking and barking and swiveling her head in search of her baby, which is actually right beside her.

Linossier is trying out scent-recognition tests too, using a fake pup fashioned from old wetsuits. To imbue her model with eau de pup, she creeps up on a sleeping baby and rubs it with a towel so gently that it doesnt wake up. She then attaches the towel to the neoprene suit and places it near the mother. (How does a baby elephant seal smell? Worse than a dog, Linossier reports.)

Its painstaking, slow-moving research, because she must be careful not to upset the sealsboth for the animals sake and in order to truly understand mother-pup interactions. Linossier has yet to analyze her data, but what shes seen so far suggests that seals hear and maybe even smell the difference between their own and another mothers pup. If nursing a strange pup is no dumb mistake, one possible explanation lies in the genes. Since one male can sire dozens of pups each year, many of the seals on the beach are related, and the mothers may be actually feeding distant kin. Linossiers next plan: genetic tests to determine relatedness.

The northern elephant seal population now numbers about 150,000 and is spreading north. The seals normally molt on California beaches, but last summer, two elephant seals from Southern California were spotted onshore in Alaska, where theyve almost never been seen before. Its a hopeful sign. Maybe they will be able to seize new opportunitiesan essential skill in an era when climate change may transform everything these animals know.

Elephant seals seem to be creatures of habit, returning to the same spots to feed and to breed every year. In a changing world, that faithful tendency could become a problem. Their preferred pupping grounds may get swamped by rising seas. The beaches where they haul out to molt may get too hot. And in the future, as waters warm and currents shift, their favorite foraging spots may no longer provide fish by the ton. During El Nio years when the central Pacific becomes warmer than usual, the seals have had trouble finding foodpossibly a preview of whats to come.

Are they too preprogrammed to adapt, or are they flexible enough to say, This space isnt working out, Ill go somewhere else? asks graduate student Rachel Holser, whose research focuses on decision-making. To investigate this question, she cant interfere with the seals fishing grounds or experimentally warm the water the creatures swim in. Instead, she uses a type of experiment common in behavior research: measuring an animals response to something its never seen before to determine how risk-averse it is. Its responses tend to be consistent across different situations: A bold animal will probably be more willing to explore new places; one that flees from an unfamiliar object will tend to stick with what it knows.

For the test, she stripped a radio-controlled toy truck down to its chassis, outfitting it with a speaker and a GoPro video camera. Then she loaded it up with a recording of the T. rex roar from Jurassic Park. (Alternative experimental stimulus: the screech of Godzilla.)

Are they too preprogrammed to adapt, or are they flexible enough to say, This space isnt working out, Ill go somewhere else?

At her desk in the Institute of Marine Sciences in Santa Cruz, she shows me video of the experiment. The GoPro image jolts and shudders as the tricked-out car crawls across the beach toward a cluster of seals. It halts roughly 10 feet from a female, who stares into the camera and grunts.

A few minutes later, we hear the bellow of T. rex, and all six seals pivot toward the camera. Holser says this is about as big a reaction as she gets out of most seals, who quickly lose interest in the contraption. That female with the death stare, however, is one of the exceptions. Another dinosaur roar, and she charges right at the camera, pink mouth gaping wide, grunting angrilythe video captures her whole palate vibrating as she barks.

After decades of research, Ao Nuevo scientists have a pretty good idea of how much disturbance the animals can tolerate without lasting effects. They carefully weigh any potential impact on fitness, like the energy wasted on confronting a radio-controlled gizmo, against the gain of better understandingin this case, how this seal and her kin might deal with other unexpected situations. The majority of animals return to normal behavior within two to five minutes, Holser says, and this seal is no exception. While shes clearly not thrilled about the interruption, the whole drama blows over very quickly.

Holser must still analyze these data, but you dont need to be a scientist to grasp that this particular seal has little fear of the unknown. Whats less clear is what that implies about her future, that of her pups, and, really, of the whole colony at Ao Nuevo. Is an aggressive female a better mom, because she protects her pup, or is she worse because shes running around the beach wasting her energy? says Holser. We dont know what the answer is.

On the screen, the seal grunts one more time, then backs off with a last dirty look. And then this extraordinary animalthis exceptional survivor, this rule-breaker among mammals, this fearless challenger of unexpected scientific thingamajigslays her head back down on the sand and drifts back to sleep.

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Meet The Deep-Diving, Ear-Splitting 4,500-Pound Rock Star of Ao Nuevo - - Bay Nature

Report: Kansas farmers plant another 6.9M acres of wheat Posted Jan 11, 2020 – hays Post

KSU NEWS SERVICE

MANHATTAN A new study from Kansas State University on the treatment of non-responding cases of bovine respiratory disease, known as BRD, conducted byHans Coetzeeand his collaborators from Iowa State University, sheds light on the relationship between drug treatments and the emergence of antimicrobial resistance.

The study, "Association between antimicrobial drug class for treatment and retreatment of bovine respiratory disease (BRD) and frequency of resistant BRD pathogen isolation from veterinary diagnostic laboratory samples," was published in the December 2019 issue of the journal PLOS ONE."

Bovine respiratory disease is one of the most important diseases facing beef cattle producers in the United States with economic losses estimated to approach $1 billion a year," Coetzee said. "Antibiotics are critical to minimize losses associated with BRD caused by bacterial infections."

Antibiotics that are used to treat BRD are broadly classified into two groups: namely those that prevent growth of the bacteria i.e., bacteriostatic and those that kill the organism i.e., bactericidal.

Although 90% of BRD relapses are reported to receive retreatment with a different class of antimicrobial, the impact of antibiotic selection bactericidal or bacteriostatic on disease outcomes and the emergence of antimicrobial resistance has not been investigated, according to Coetzee.

The focus of the study is determining the association between antimicrobial class selection for treatment and retreatment of BRD relapses and antimicrobial susceptibility ofMannheimia haemolytica,Pasteurella multocidaandHistophilus somni.Pathogens were isolated from samples submitted to the Iowa State University Veterinary Diagnostic Laboratory from January 2013 to December 2015. A total of 781 isolates with corresponding animal case histories, including treatment protocols, were included in the analysis.

"Our overall interpretation of the data suggests that there is direct association between the number of treatments to which an animal was exposed and the emergence of antibiotic resistance in samples submitted to a veterinary diagnostic laboratory for analysis," Coetzee said. "In addition, these exploratory data suggest that BRD treatment protocols involving first-line treatment with a bacteriostatic antibiotic followed by second-line treatment with a bactericidal antibiotic may increase the probability of isolating BRD bacteria that are resistant to antibiotics."

While this observation suggests that consideration should be given to the mechanism of action of the antibiotic when selecting drugs for retreatment of non-responding cases of BRD, Coetzee said further research is needed to determine the clinical relevance of this finding in livestock production systems.

Coetzee is a professor and head of the anatomy and physiology department at theCollege of Veterinary Medicine. He has published 160 peer-reviewed scientific papers and has received more than $10 million in research funding.

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Report: Kansas farmers plant another 6.9M acres of wheat Posted Jan 11, 2020 - hays Post

Free whitepaper: Anatomy of work: a look at how employees really spend their time at work – The Drum

As organizations rely more and more heavily on collaborative tools and software platforms (IDC predicts that the market for collaborative applications will increase to $26.6BN by 2030), it has become harder to track what kind of work employees are actually getting up to.

A new Anatomy of Work Index whitepaper from Asana is all about learning how marketers actually spend their days in the office, and analyzing their overall rate of productivity. It uses this data, which has been drawn from a pool of 10,000 knowledge workers globally and includes workers in roles such as chief marketing officer, head of brand and senior marketing manager, to see where agencies and brands can improve in order to start becoming more effective in the 2020's.

Some of the key learnings include the fact that the majority of global employees (60%) spend most of their time on work about work, which could be emailing someone about plans or doing practical, non-creative tasks such as micro-managing others. In comparison, just 40% spend time on skilled work like executing a campaign, and this highlights the fact that most workers are losing the battle when it comes to finding time to embrace more thoughtful, deeper work tasks.

Even more worrying is the fact that polled employees are only spending 27% of their time at work on skills based work; the craft they were actually trained and hired to carry out. Therefore it is high time we found a solution, and this whitepaper will help to provide practical advice on how you can create a more inspired team thats set up to execute their roles much more effectively.

Asanas Anatomy of Work index also explores how unbalanced workloads are crippling employees and negatively impacting their productivity. The index has found 26% of employees have too much work to do, which subsequently drives stress and feelings of being unsettled. Its goal is to inspire you to find ways to ensure workers are doing their 9-to-5 more effectively, and not wasting their time on things that create unhappiness in the workplace.

Another fascinating insight the index provides is around how many hours a day workers find themselves distracted, and youll be able to compare how UK workers compare to the US, Germany, Australia, and even Japan. The fact, on average, 1 hour and 4 minutes is wasted daily by knowledge workers globally due to distractions or procrastination shows how much room there is for improvement.

The Anatomy of Work examines how to break down those barriers that stop workers from being productive and showing how technology, such as Asanas own work management tool, can help create a system that benefits everybody when applied correctly and not just at a whim.

The most forward-thinking organisations in the world know how to leverage time-saving work management software to reimagine their workplace, and this forward-thinking piece of research will show why taking control of workloads and collaborating more thoughtfully is a must if your workers are to reach the next level.

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Free whitepaper: Anatomy of work: a look at how employees really spend their time at work - The Drum

Liz Bonnin: I was nearly devoured by my tiger project in Nepal – The Times

Wildlife TV presenter LizBonnin recalls doing a masters in wild animal biology and feeling like shed bitten off way more than she could chew when trying to plan an overseas trip to study the eating habits of big cats in a national park near Kathmandu

Interview by Larissa Nolan

I studied biochemistry at Trinity College Dublin. I have always been passionate about science. It is my first love and it always will be understanding how living things work, down to the chemical equations that explain them.

I had done a project on degenerative diseases and applied for a PhD as the next logical step, and I was accepted at Oxford. But I wanted to work more on learning about how to protect the planet and wildlife, which is how I ended up doing a masters in wild animal biology in the Royal Veterinary College and Zoological Society of London instead.

I wrote to them. At first they said, Well consider your application and I said, No, no can I please come in and

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Liz Bonnin: I was nearly devoured by my tiger project in Nepal - The Times

Antibiotics could be promising therapy for certain forms of dementia – Specialty Medical Dialogues

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USA: Frontotemporal dementia is the most common type of early-onset dementia. It typically begins between ages 40 and 65 and affects the frontal and temporal lobes of the brain, which leads to behavior changes, difficulty speaking and writing, and memory deterioration. Now, a recent study published in the journal Human Molecular Genetics has found a class of antibiotics called aminoglycosides to be a promising treatment for frontotemporal dementia.

These results could be promising for drug development. Currently, there are no effective therapies for any type of dementia.

A subgroup of patients with frontotemporal dementia has a specific genetic mutation that prevents brain cells from making a protein called progranulin. Although progranulin is not widely understood, its absence is linked to the disease.

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These patients brain cells have a mutation that prevents progranulin from being made. The researchers found that by adding a small antibiotic molecule to the cells, they could trick the cellular machinery into making it, said Matthew Gentry, a co-author of the study and the Antonio S. Turco Endowed Professor in the Department of Molecular and Cellular Biochemistry.

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Haining Zhu, Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, and colleagues discovered that after the addition of aminoglycoside antibiotics to neuronal cells with this mutation, the cells started making the full-length progranulin protein by skipping the mutation.

The researchers found two specific aminoglycoside antibiotics Gentamicin and G418 were both effective in fixing the mutation and making the functional progranulin protein. After adding Gentamicin or G418 molecules to the affected cells, the progranulin protein level was recovered up to about 50 to 60%.

After this preclinical proof of concept study, the next step is to study the antibiotics effects on mice with the mutation that causes frontotemporal dementia, Zhu says. Another focus is to possibly develop new compounds from Gentamicin and G418 that could be safer and more effective. Although Gentamicin is an FDA-approved medication, its clinical usage is limited as it is associated with a number of adverse side effects.

If we can get the right resources and physician to work with, we could potentially repurpose this drug. This is an early stage of the study, but it provides an important proof of concept that these aminoglycoside antibiotics or their derivatives can be a therapeutic avenue for frontotemporal dementia, said Zhu.

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The study, Frontotemporal dementia nonsense mutation of progranulin rescued by aminoglycosides, is published in the journal Human Molecular Genetics.

DOI: https://doi.org/10.1093/hmg/ddz280

Disclaimer: This site is primarily intended for healthcare professionals. Any content/information on this website does not replace the advice of medical and/or health professionals and should not be construed as medical/diagnostic advice/endorsement or prescription. Use of this site is subject to our terms of use, privacy policy, advertisement policy. 2020 Minerva Medical Treatment Pvt Ltd

Medha Baranwal joined Medical Dialogues as an Editor in 2018 for Speciality Medical Dialogues. She covers several medical specialties including Cardiac Sciences, Dentistry, Diabetes and Endo, Diagnostics, ENT, Gastroenterology, Neurosciences, and Radiology. She has completed her Bachelors in Biomedical Sciences from DU and then pursued Masters in Biotechnology from Amity University. She has a working experience of 5 years in the field of medical research writing, scientific writing, content writing, and content management. She can be contacted atmedha@medicaldialogues.in. Contact no. 011-43720751

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Source: With inputs from Human Molecular Genetics

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Antibiotics could be promising therapy for certain forms of dementia - Specialty Medical Dialogues

Role Of Vitamin-D Supplementation In TB/HIV Co-Infected Patients | IDR – Dove Medical Press

Birhanu Ayelign, 1 Meseret Workneh, 1 Meseret Derbew Molla, 2 Gashaw Dessie 2

1Department of Immunology and Molecular Biology, School of Biomedical And Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; 2Department of Biochemistry, School of Medicine, College of Medicine And Health Sciences, University of Gondar, Gondar, Ethiopia

Correspondence: Birhanu Ayelign Email birhanuayelign42@gmail.com

Objective: This review aimed to assess the role of vitamin D supplementation on the decrement of mortality and morbidity rate among tuberculosis (TB)/human immune deficiency virus (HIV) co-infected clients.Method: Pub Med, google scholar and google search were accessed to find out all document to describe this review article.Results: Nowadays TB/HIV co-infection has become a major global concern, particularly in low and middle-income countries. Mycobacterium tuberculosis and HIV infections are co-endemic and more susceptible to the progression of TB. Immunosuppression associated with HIV is a strong risk factor for the reactivation of latent TB to the active form. Immune cells like macrophages recognized Mycobacterium tuberculosis through TLR2/1, and it increases the expression of the vitamin D receptor (VDR) and CYP27B1. The synthesis of 1,25-dihydroxy vitamin D promotes VDR-mediated transactivation of the antimicrobial peptide cathelicidin and the killing of intracellular Mycobacterium tuberculosis. Cathelicidins have a direct antimicrobial effect through membrane disruption. Besides, it has also antiviral effects via inhibition of retrovirus (HIV) replication. In fact, as some studies showed, there was a lower induction of cathelicidin in monocytes who have low vitamin D levels.Conclusion: Therefore, vitamin D supplementation can be directly involved in the reduction of TB/HIV co-infection and its progression.

Keywords: vitamin D, tuberculosis, HIV

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Role Of Vitamin-D Supplementation In TB/HIV Co-Infected Patients | IDR - Dove Medical Press

Mouse Lemurs Just Might Be the Next Big Thing in Genetics – Nature World News

Jan 08, 2020 11:04 AM EST

There are 500 animals studied so far in the mouse lemur project, a collaboration that aims to parse the genetics of this diminutive, prosimian primate. It is the brainchild of Stanford biochemist Mark Krasnow.

Because all 24 species of mouse lemurs look similar, the most reliable way for scientists to tell them apart is through genetic testing. (Scientists have recently identified three new species of mouse lemurs in Madagascar.)

They are quite possibly the answer to medical researchers' dreams.

This world's smallest primate may soon replace fruit flies, worms, and even mice as the primary lab animal for scientific research.

According to Stanford University School of Medicine researchers, they have the potential to serve as an ideal model for a wide range of primate biology, behavior, and medicine, including cardiovascular disease and Alzheimer's disease.

Mice, fruit flies, and worms as genetic models have routinely failed to mimic many aspects of primate biology, including many human diseases, said Mark Krasnow, MD, Ph.D., professor of biochemistry.

Krasnow and his colleagues turned to the mouse lemur and began conducting detailed physiologic and genetic studies on them.

It was reported that they already have identified more than 20 individual lemurs with unique genetic traits, including obesity, high cholesterol, high blood sugar, cardiac arrhythmias, progressive eye disease and motor and personality disorders.

The researchers hope it will soon become a genetic model organism that will help us better understand many aspects of primate biology, behavior, and health, including lemur and human diseases.

According to the June issue of GENETICS, Ezran et al.'s genetic research on these primates began as a project for three high school laboratory interns to find an appropriate model organism for primate genetics.

Mouse lemurs are more human than mice, as genetic research on mice has led to countless important discoveries, but their physiology and behavior differ in many ways from that of humans and other primates. They potentially rival the common laboratory mouse Mus musculus, at least for certain questions.

Mice, fruit flies, and worms were the prototypical lab specimen because they were inexpensive to maintain, easy to study, and reproduced quickly enough to offer researchers a constant stream of samples. According to Krasnow, MD, Ph.D., a professor of biochemistry at Stanford University, the genetic makeup of the 3 animals hasn't been a close enough match to humans to work well for the studies today's researchers need to conduct.

Krasnow's project is studying a large population of grey and brown mouse lemurs - Microcebus murinus and Microcebus rufus, respectively - in the wild to work out how their genes link to differences in biology, health, and behavior.

Other than being closely related to humans, they still have many of the advantages of mice in terms of small size, rapid reproduction, and relatively large litters.

These researchers hope that continued study of these abundant primates could lead to a better understanding, and possibly better treatments, of these and other conditions in lemurs and humans.

RELATED ARTICLE: DNA Analysis Helps Researchers Identify New Mouse Lemur Species

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Mouse Lemurs Just Might Be the Next Big Thing in Genetics - Nature World News