Tech

Sortilin may hold the key to combat pancreatic cancer more effectively

image: Caption Pancreatic cancer cells in control (A) vs treatment by anti-sortilin targeting drug (B). When sortilin is targeted, pancreatic cancer cells partially lose attachment and cannot migrate. Scale bars = 50um.

Image: 
Hubert Hondermarck's Laboratory

Philadelphia, August 20, 2020 - Pancreatic cancer has an extremely poor prognosis; it is the third most common cause of cancer deaths in the United States. In a novel study published in The American Journal of Pathology, published by Elsevier, scientists report the discovery of an increased level of the neuroprotein sortilin in pancreatic cancer cells that may open up the way to developing more effective treatment.

"There is currently no good therapy for pancreatic cancer," explained lead investigator Hubert Hondermarck, PhD, School of Biomedical Sciences and Pharmacy and Hunter Medical Research Institute at the University of Newcastle, Australia. "What we need is a targeted therapy that could slow down the rapid progression of the disease to allow more time for chemotherapy and radiotherapy to be more effective."

The neuronal membrane protein sortilin is emerging as a key player in the regulation of neuronal viability and function, and there are increasing indications that it is involved in the deregulation of cancer cell viability. Sortilin is overexpressed in breast, lung, and thyroid cancer; it can promote cancer cell invasion in glioblastoma; and it participates in cancer cell adhesion and metastasis in colorectal cancer. However, its expression and impact in pancreatic cancer was not previously known.

In this study, investigators examined several pancreatic cancer cell lines alongside pancreatic ductal epithelial cells and established that sortilin expression was higher in the cancer cells, as demonstrated by Western blot and mass spectrometry. The increased sortilin level in pancreatic cancer cells was confirmed by immunohistochemistry in a series of 99 human pancreatic adenocarcinomas compared to 48 normal pancreatic tissues.

Furthermore, sortilin was found to contribute to pancreatic cancer invasion in vitro through potentially maintaining the focal adhesion kinase (FAK) signaling pathway. Researchers also found that sortilin levels were higher in female pancreatic cancer patients compared to males. "Our finding of higher sortilin expression in female patients suggests a possible regulation of sortilin gene expression by estrogen receptors, but further functional analyses are needed to confirm this hypothesis," noted Dr. Hondermarck.

The main issue with pancreatic cancer is the local invasiveness of the tumor that leads to the destruction of the pancreas, rapidly causing death. This study showed that inhibiting sortilin with specific drugs or immunotherapy leads to a strong decrease in pancreatic cancer cell invasiveness. Therefore, specifically targeting sortilin is likely to complement and improve the efficacy of existing treatments. However, no statistically significant association was found between sortilin expression and pancreatic cancer aggressiveness. Therefore, although sortilin contributes to pancreatic cancer cell invasion, it is likely not the only factor involved.

"Together, these data reveal that sortilin contributes to pancreatic cancer invasion and is a potential therapeutic target," commented Dr. Hondermarck. "This discovery may lead to the development of more efficient treatment against the disease."

Pancreatic cancer is one of the most aggressive malignancies, with less than nine percent patient survival after five years. It is the seventh most common cause of cancer deaths worldwide and the third most common in the US. The most common type is pancreatic adenocarcinoma, which accounts for 90 percent of cases. Current therapeutic approaches include surgery, radiotherapy, and chemotherapy. Surgery is the most common treatment for early-stage pancreatic cancer, but it can be performed in less than twenty percent of patients. The main drug currently used to treat pancreatic cancer, gemcitabine, has only a limited therapeutic effect.

Credit: 
Elsevier

International team identifies a new regulatory pathway in bladder cancer

image: International team identifies a new regulatory pathway in bladder cancer

Image: 
Insilico Medicine

August 20th, 2020, Hong Kong - Researchers from Johns Hopkins University in collaboration with Insilico Medicine announce the publication of a new research paper titled "GULP1 regulates the NRF2-KEAP1 signaling axis in urothelial carcinoma" in Science Signaling.

The KEAP1-NRF2 pathway plays a key role in cancer prevention and protective cellular responses to oxidative and electrophilic stress. In normal and premalignant tissues the signaling pathways activated by NRF2 prevent cancer initiation and progression, but in fully malignant cells disruption of the KEAP1-NRF2 pathway results in the transactivation of NRF2 target genes, consequently inducing cell proliferation and other phenotypic changes in cancer cells.

In this study, the researchers from John Hopkins University in collaboration with Insilico Medicine analyzed the protein GULP1 and its influence on the KEAP1-NRF2 pathway. The results demonstrated that GULP1 knockdown leads to tumor cell proliferation in vitro and enhanced tumor growth in vivo, as well as the resistance to cisplatin treatment. In parallel with decreased GULP1 expression, an increased expression of antioxidant genes in cisplatin-resistant cells was observed. Furthermore, low or no expression of GULP1 was observed in most cisplatin nonresponder cases.

Together, the findings demonstrate that GULP1 is a KEAP1 binding protein that regulates KEAP1-NRF2 signaling in UCB, and that promoter hypermethylation of GULP1 is a potential mechanism of GULP1 silencing.

"I am extremely happy to see authors from Insilico Medicine on this important paper by one of the world's top research groups. While KEAP1-NRF2 pathway is a major signaling axis in bladder cancer and other solid malignancies, targeting of this complex pathway remains challenging. Building on the knowledge generated in this study, we will use novel computational platforms developed at Insilico Medicine, such as Pandomics, and its integral component called Target ID, to focus on identifying and validating novel compounds that could inhibit this signaling network with high specificity, efficacy and safety", said Alex Zhavoronkov, PhD, CEO of Insilico Medicine.

Credit: 
InSilico Medicine

Dinosaurs' unique bone structure key to carrying weight

image: Researchers recently learned of the unique weight-saving adaptation to dinosaur bone that enabled 8,000 pound dinosaurs like hadrosaurs to move easily. Illustration by Karen Carr.

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SMU

DALLAS (SMU) - Weighing up to 8,000 pounds, hadrosaurs, or duck-billed dinosaurs were among the largest dinosaurs to roam the Earth. How did the skeletons of these four-legged, plant-eating dinosaurs with very long necks support such a massive load?

New research recently published in PLOS ONE offers an answer. A unique collaboration between paleontologists, mechanical engineers and biomedical engineers revealed that the trabecular bone structure of hadrosaurs and several other dinosaurs is uniquely capable of supporting large weights, and different than that of mammals and birds.

"The structure of the trabecular, or spongy bone that forms in the interior of bones we studied is unique within dinosaurs," said Tony Fiorillo, SMU paleontologist and one of the study authors. The trabecular bone tissue surrounds the tiny spaces or holes in the interior part of the bone, Fiorillo says, such as what you might see in a ham or steak bone.

"Unlike in mammals and birds, the trabecular bone does not increase in thickness as the body size of dinosaurs increase," he says. "Instead it increases in density of the occurrence of spongy bone. Without this weight-saving adaptation, the skeletal structure needed to support the hadrosaurs would be so heavy, the dinosaurs would have had great difficulty moving."

The interdisciplinary team of researchers used engineering failure theories and allometry scaling, which describes how the characteristics of a living creature change with size, to analyze CT scans of the distal femur and proximal tibia of dinosaur fossils.

The team, funded by the National Science Foundation Office of Polar Programs and the National Geographic Society, is the first to use these tools to better understand the bone structure of extinct species and the first to assess the relationship between bone architecture and movement in dinosaurs. They compared their findings to scans of living animals, such as Asian elephants and extinct mammals such as mammoths.

"Understanding the mechanics of the trabecular architecture of dinosaurs may help us better understand the design of other lightweight and dense structures," said Trevor Aguirre, lead author of the paper and a recent mechanical engineering Ph.D. graduate of Colorado State University.

The idea for the study began ten years ago, when Seth Donahue, now a University of Massachusetts biomedical engineer and expert on animal bone structure, was invited to attend an Alaskan academic conference hosted by Fiorillo and other colleagues interested in understanding dinosaurian life in the ancient Arctic. That's where Fiorillo first learned of Donahue's use of CT scans and engineering theories to analyze the bone structure of modern animals.

"In science we rarely have lightning bolt or 'aha' moments," Fiorillo says. "Instead we have, 'huh?' moments that often are not close to what we envisioned, but instead create questions of their own."

Applying engineering theories to analyze dinosaur fossils and the subsequent new understanding of dinosaurs' unique adaptation to their huge size grew from the 'huh?' moment at that conference.

Credit: 
Southern Methodist University

Exoskeleton research marches forward with NIST study on fit

video: The optical tracking system captures and recreates the movement of the exoskeleton markers (red and pink clusters) and the human markers (orange and blue clusters) in a digital space. Discordant movement between the human and exoskeleton markers could indicate a poor fit that may lead to pain or injury.

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NIST

A shoddily tailored suit or a shrunken T-shirt may not be the most stylish, but wearing them is unlikely to hurt more than your reputation. An ill-fitting robotic exoskeleton on the battlefield or factory floor, however, could be a much bigger problem than a fashion faux pas.

Exoskeletons, many of which are powered by springs or motors, can cause pain or injury if their joints are not aligned with the user's. To help manufacturers and consumers mitigate these risks, researchers at the National Institute of Standards and Technology (NIST) developed a new measurement method to test whether an exoskeleton and the person wearing it are moving smoothly and in harmony.

In a new report, the researchers describe an optical tracking system (OTS) not unlike the motion capture techniques used by filmmakers to bring computer-generated characters to life.

The OTS uses special cameras that emit light and capture what is reflected back by spherical markers arranged on objects of interest. A computer calculates the position of the labeled objects in 3D space. Here, this approach was used to track the movement of an exoskeleton and test pieces, called "artifacts," fastened to its user.

"The ultimate goal is to strap these artifacts on to the person, put on the exoskeleton, compare the difference in the person wearing these artifacts versus the exoskeleton and see if they move the same," said Roger Bostelman, a robotics engineer at NIST and lead author of the study. "If they move in concert with one another, then it fits correctly. If they move differently, it's not fit correctly, and you could determine adjustments from there."

In the new study, the NIST researchers aimed to capture the motion of the knee -- one of the body's relatively simple joints, Bostelman said. To assess the measurement uncertainty of their new approach, they constructed two artificial legs as test beds. One featured an off-the-shelf prosthetic knee, while the other incorporated a 3D-printed knee that more closely mimicked the real thing. Metal plates were also fastened to the legs with bungee cords to represent exoskeletal limbs or test artifacts attached to the body.

After fixing markers to the legs and plates, the team used the OTS and a digital protractor to measure knee angles throughout their full range of motion. By comparing the two sets of measurements, they were able to determine that their system was capable of accurately tracking leg position.

The tests also established that their system could calculate the separate motions of the legs and exoskeletal plates, allowing the researchers to show how closely aligned the two are while moving.

To adapt their method to be used on an actual person's leg, the team designed and 3D-printed adjustable artifacts that -- like a knee brace -- fit to the user's thigh and shin. Unlike the skin, which shifts due to its own elasticity and contracting muscles underneath, or skin-tight clothing that may be uncomfortable for some, these artifacts offer a rigid surface to stably and consistently place markers on different people, Bostelman said.

The team mounted the knee artifacts and a full-body exoskeleton garnished in reflective markers onto Bostelman. With the OTS keeping a close eye on his legs, he proceeded to perform several sets of squats.

The tests showed that most of the time, Bostelman's leg and the exoskeleton moved in harmony. But for brief moments, his body moved while the exoskeleton didn't. These pauses could be explained by the way in which this exoskeleton works.

To provide extra strength, it uses springs, which engage and disengage as the person moves. The exoskeleton pauses when the springs shift modes, however, temporarily resisting the user's movement. By detecting the nuances of the exoskeleton's function, the new measurement method demonstrated its attention to detail.

The raw data alone doesn't always reveal whether a fit is adequate. To improve the accuracy of their method, Bostelman and his team will also use computational algorithms to analyze the positional data.

"The next steps are to develop artifacts for the arm, for the hip and basically all the joints this exoskeleton is supposed to be in line with and then perform similar tests," Bostelman said.

Credit: 
National Institute of Standards and Technology (NIST)

New database shows more than 20% of nursing homes still report staff, PPE shortages

Nearly half of all COVID-19 deaths in the United States have occurred among nursing home residents, whose age, chronic medical conditions, and congregate living quarters place them and their caregivers at high risk of contracting the disease.

And yet, six months into the pandemic, more than 20 percent of nursing homes in the US continue to report severe shortages of staff and personal protective equipment (PPE), according to a new study.

"Twenty percent is a lot, given where we are in the course of this pandemic. I would have hoped by month six we would be close to zero percent," says Brian E. McGarry, Ph.D., Assistant Professor of Geriatrics/Aging and Public Health Sciences at the University of Rochester Medical Center (URMC). He is lead author of a paper released as a fast track ahead of print article by the journal Health Affairs. "While there has been some shifting in which nursing homes have been reporting these problems, from a national level, we're still not on the right trajectory."

The study, conducted in collaboration with David C. Grabowski, Ph.D., Professor of Health Care Policy at Harvard Medical School, and Michael L. Barnett, M.D., M.S. Assistant Professor of Health Policy and Management at Harvard's T.H. Chan School of Public Health, is among the first to report results from a new Centers for Medicare and Medicaid Services (CMS) COVID-19 Nursing Home Database.

The database includes responses from more than 15,000 nursing homes and other long-term care facilities--or 98 percent of the US total--regarding the impact of COVID-19 on staff and residents. The database is far from perfect, McGarry says. Some of the questions nursing homes respond to are "ambiguous" and could be honed to elicit more details.

Nonetheless, based on nursing home responses submitted for the database from May 18 to June 14, and from June 24 to July 19, the researchers determined that:

Rates of both staff and PPE shortages did not meaningfully improve from May to July.

The facilities most likely to report shortages were those with COVID-19 cases among residents and staff, those serving a high proportion of Medicaid recipients, and those that score lower on a five-star quality rating system used by CMS.

"Having a shortage of any type of staff affects every aspect of clinical care, whereas a shortage of any PPE element can break infection control protocols," the study says.

N95 masks and gowns continued to be the most commonly reported PPE shortages, with gown shortages easing slightly by July 19. Though the federal government promised in May to provide nursing homes with a two-week supply of PPE, "many nursing homes reported that they did not receive adequate PPE through this initiative."

And although the Centers for Disease Control called for nursing homes to develop plans to mitigate staffing shortages, "many nursing homes struggled with staffing prior to COVID-19, and shortages have reportedly been magnified because many staff are unable or unwilling to work in these conditions," the study reports. Nurses, nursing aides and "other staff" continued to be staff categories with the most shortages.

"It is concerning, although not unexpected, that more disadvantaged and lower quality nursing homes, such as those with a higher percent of revenue from Medicaid or those with lower star ratings, have worse staff shortages. These are the facilities whose profit margins will be necessarily lower due to the underpayment of Medicaid for nursing home costs," the study says.

"This is not just about bad nursing homes doing a bad job," McGarry adds. "Nursing homes are very much at the mercy of the levels of infection in the communities around them. COVID-19 is indiscriminate. It doesn't care whether you're a five-star facility or not. The most effective way to prevent COVID-19 outbreaks in nursing homes is reducing the prevalence of the disease in the communities they serve."

In addition, the researchers recommend that:

Top priority be put on insuring that all nursing homes have a minimally sufficient supply of PPE "if policymakers intend to save as many lives as possible."

Future stimulus packages provide additional, targeted financial support for direct patient care and supplies in nursing homes with more disadvantaged populations, coupled with appropriate oversight to ensure funds are used appropriately.

States with the severest shortages of nursing home staff "prioritize their nursing homes' resilience" to deal with outbreaks.

Medicare continue its commitment to gathering and disseminating information on nursing homes' available resources, but also update survey questions to reflect current realities of the pandemic, including testing turnaround time.

Credit: 
University of Rochester

Study focuses on low-carb, high-fat diet effect on older populations

A new study, published in Nutrition and Metabolism, from researchers with the University of Alabama at Birmingham's Nutrition Obesity Research Center observed improvements in body composition, fat distribution and metabolic health in response to an eight-week, very low-carbohydrate diet.

Older adults with obesity are at particularly high risk of developing cardiometabolic disease such as Type 2 diabetes and cardiovascular disease. Rather than total fat mass, deposition of fat in certain areas, such as the abdominal cavity and skeletal muscle, may confer this greatest risk of disease development.

The study's lead author is Amy Goss, Ph.D., RDN, an assistant professor with UAB's Department of Nutrition Sciences. Goss says her team aimed to determine if a very low-carbohydrate, or VLCD, high-fat diet would deplete these fat depots and preserve lean mass without intentional caloric restriction in older adults with obesity, thereby improving outcomes related to cardiometabolic disease, such as insulin sensitivity and the lipid profile.

"After the eight-week intervention, despite the recommendation to consume a weight-maintaining diet, the group consuming the very low-carbohydrate diet lost more weight and total fat mass than the control diet group," Goss said.

Egg consumption was an important part of the VLCD prescription. Goss and her team provided eggs to the participants in this diet group and asked them to consume at least three per day.

"While eggs were a part of this study, we can't conclude that our findings are a result of daily egg consumption; but I think what we can conclude is that whole eggs can be incorporated into the diet in a healthful way without adversely impacting blood cholesterol in older adults," she said.

The primary difference in fat lost between the two groups was from the abdominal cavity and the skeletal muscle depots.

"We also found significant improvements in the overall lipid profile that would reflect decreased risk of cardiovascular disease," Goss said. "Further, insulin sensitivity improved in response to the very low-carbohydrate diet reflecting reduced risk of Type 2 diabetes. Overall, we observed improvements in body composition, fat distribution and metabolic health in response to an eight-week, very low-carbohydrate diet."

VLCD effect on diabetes

Goss says VLCDs are a therapeutic option for many conditions, including Type 2 diabetes, obesity and non-alcoholic fatty liver disease.

"This study extends previous research to show that it can be a safe, therapeutic option for older adults in their 70s experiencing obesity," she said. "This is the first study to demonstrate depletion of 'metabolically harmful' fat depots while preserving skeletal muscle during weight loss in response to a VLCD in older adults."

Goss adds that there is quite a bit of evidence about the benefits of a very low-carbohydrate diet in younger populations, and this study was one of the first to test this dietary approach to improve outcomes related to obesity in adults older than age 65 -- a population at particularly high risk of other diseases and in need of therapeutic interventions to improve health while preserving skeletal muscle mass to prevent or delay functional decline with age.

A good or bad egg?

"Historically, eggs have received a bad rap beginning with the nutrition guidelines on egg consumption set forth by the American Heart Association in 1968," Goss said. "It was recommended that no more than three whole eggs be consumed each week."

Goss adds that the concern stemmed from the cholesterol and saturated fat content of the egg yolk. Since then, these recommendations have loosened because more recent research demonstrated the negligible impact of dietary cholesterol on blood cholesterol. And just this month, the Dietary Guideline Advisory Committee issued recommendations to increase the consumption of eggs across the lifespan, including pregnant and lactating women, and also as a first food for infants and toddlers.

"This historical first for the Dietary Guidelines Committee recognized eggs as an important, nutrient-rich food source, as eggs are a rich source of protein, choline, B12, selenium, vitamin D and a long list of other nutrients vital to growth and development as well as maintenance of muscle mass," Goss said.

Credit: 
University of Alabama at Birmingham

Downstream effects: Sturgeon lifespan, fertility vary strikingly with river conditions

image: New research has found that pallid sturgeon stocked in a northerly segment of the Missouri River live an average of three times longer, produce roughly 10 times as many eggs and weigh up to seven times more than specimens stocked downriver. The findings represent a dramatic example of how environmental conditions -- in this case, fast-flowing channels introduced via human intervention -- can shape the life cycle of a species.

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Photo: Sam Stukel, U.S. Fish and Wildlife Service / Illlustration: University of Nebraska-Lincoln

As he discussed how the pallid sturgeon has responded to differing conditions along the Missouri River, the mind of soft-spoken fish ecologist Mark Pegg drifted to a Def Leppard lyric inspired by Neil Young.

"What is the old song? 'It's better to burn out than to fade away?' In this case, I'm not sure that's true," said Pegg, a professor with the University of Nebraska-Lincoln's School of Natural Resources.

Pegg was referring not to the existential fate of the shovel-nosed, long-lived endangered species, but to the life cycles of individual specimens. He was talking about the impressive developmental flexibility, but also the troubling developmental deficits, that some specimens have shown in the face of human intervention on the Missouri -- the power of nurture, or lack thereof, revealed by an unprecedented new study.

The study found that pallid sturgeon stocked around the lower basin of Nebraska, Iowa and Missouri live an average of just 19.8 years -- nearly three times shorter than in the upper basin of Montana and North Dakota, where the average was an estimated 56.4 years.

Combined with the fact that females in the lower basin weighed an average of seven times less than in the upper basin, that altered trajectory also seemed to dramatically influence reproduction. The shorter-lived female specimens appeared to compensate by reaching sexual maturity at around age 10, compared with age 17 in their longer-lived counterparts. Despite the head start, though, their looming demise caught up with them: The lower-basin females spawned between three and 11 times, well below the range of 13-20 times among females in the upper basin. According to the estimates of the research team, the lower-basin females consequently laid about 10 times fewer eggs over their lifetimes.

The researchers, led by the University of Georgia's Martin Hamel, came to the striking conclusions by analyzing existing data gathered from both wild and hatchery-raised sturgeon -- more than 1,200 in total. In the mid-2000s, a cadre of agencies began regularly measuring and monitoring the age, size and fertility of wild specimens in an effort to learn more about threats to the endangered species. But an even earlier effort, begun in the mid-1990s, sought to supplement the species' declining numbers.

"So they grabbed whatever fish they could that were of reproductive size and age and started making little sturgeon," Pegg said.

The sturgeon they initially grabbed and set to spawning in hatcheries came from the upper basin in Montana. When it came time to release those offspring into the Missouri River, the agencies stocked them across both the upper basin, where their parents had lived, and the lower basin.

Years later, that decision would manifest as a boon for Hamel, Pegg and their colleagues, Kirk Steffensen of the Nebraska Game and Parks Commission and Jonathan Spurgeon of the University of Arkansas at Pine Bluff. Because of it, the researchers had access to an exceedingly rare dataset: substantial numbers of genetically similar specimens left to grow and mature in two environments separated by more than a thousand miles. Any major differences in their development, then, would almost certainly arise from differences in those environments -- an ichthyological analog of studying identical human twins raised in different households.

"Replicating that (approach) is horribly difficult, especially in Mother Nature's lab," Pegg said. "We just don't have the space, time or resources to really do that. So this was more of a moment of serendipity than any real planning on our part.

"We knew where the fish were coming from, and we could start to look at how they were actually responding to their new environment."

Pegg said the extreme developmental differences the team discovered between the upper- and lower-basin populations probably speak to at least two major differences in their environments: depth and currents. Though the upper basin has undergone some human-related change over the past few centuries, it more closely resembles the relatively shallow, slow-moving river it was before the arrival of white colonialists. Even where it is deeper and faster, he said, it still offers some slower-flowing refuges where larvae and finger-length juveniles can settle and grow without much stress. Those refuges also house food, from algae to minnows, that make life easier for larvae and adults alike.

The lower basin, by contrast, features more reservoirs and deeper channels that were carved into the river to promote currents and ease the conveyance of ships down the river. The success of those efforts, Pegg said, has probably forced the sturgeon to invest an inordinate amount of time and energy essentially swimming in place -- investments that likely slow growth among juveniles and keep females from putting on the weight that is strongly tied to fertility.

"They have to spend a lot of energy maintaining position, as opposed to up in Montana ... where they have the ability to get bigger because they're not spending a lot of energy keeping themselves in the water column.

"We're sort of shortchanging the fish down here in a lot of different ways."

The team's study follows in the wake of others that have demonstrated the ability of organisms, including fish, to adjust their development and behavior in response to their environments -- and on timelines far too short for genetic-based evolution to explain. Some research, for instance, has tracked the fates of largemouth bass that were transported from Florida to bodies of water farther north. But from what Pegg has seen, no prior studies have examined the phenomenon on such a wide scale, either geographically or numerically.

"To my knowledge, this is the one and only that's covering literally 2,500 miles of river or so," he said of the study, published in the journal Scientific Reports. "From a fish perspective, this is pretty unprecedented, as far as I know, in the literature.

"Most of the other (similar studies) were dealing with tanks of fish or, at best, a pond of fish with maybe a few hundred. But we're talking about -- at least in the lower part of the river, where we really saw that change -- literally thousands of individuals. So I think from the magnitude of sample size, our effect is pretty large, in terms of what we can say about the results."

And what they can say, according to Pegg, is that the findings make a dramatic and literal case for the downstream effects of environmental change. While those effects may not be solely responsible for the species' endangered status, they probably account for some of the difficulty in resuscitating its population, he said. But they might also point the way to more successful conservation efforts, and more careful planning, down the line.

"What it really highlights is that we do need to be careful about just willy-nilly stocking or reintroducing fish or birds or mammals into places they may or may not be well-adapted to," he said. "At least in this case, (the sturgeon) seem to be holding on and maybe have adjusted to their new environments a little better than some other places. But we aren't necessarily producing a viable population based on those original stockings (to the extent) that we'd hoped for. So taking care to properly think through and plan with the best science we have available to us is certainly one of the big take-home messages."

Credit: 
University of Nebraska-Lincoln

A smart eye mask that tracks muscle movements to tell what 'caught your eye'

video: This video shows real-time performance of Chesma tracking eye movement

Image: 
S. Zohreh Homayounfar

Integrating first-of-its-kind washable hydrogel electrodes with a pulse sensor, researchers from the University of Massachusetts Amherst have developed smart eyewear to track eye movement and cardiac data for physiological and psychological studies. The eyewear--known as Chesma and presented August 20 in the journal Matter--provides accurate measurements in an everyday environment without compromising users' comfort.

"Our mask can track people's eye movement as they're shown images, so you can start to understand what they're paying attention to, for how long, whether they keep finding other places to look," says senior author Trisha L. Andrew of the University of Massachusetts Amherst.

Current technology for eye movement tracking relies on electrooculography (EOG), a technique designed over 50 years ago to measure the eye's electrical potential changes. "The problem is that you have to stick those adhesive electrodes on your face," says Andrew. "But people tend to be a little finicky about stuff put on their face, unsurprisingly."

One challenge in designing smart wearables is developing products that provide both accuracy and comfort. To achieve that, Andrew and her colleagues developed a novel hydrogel electrode by growing polymers on fabrics. Reaching the nooks and cranny of the fiber pattern, the hydrogel polymer bonds to and covers the fabric's topology, resulting in a mechanically stable coating that is imperceptible to one's eye and touch.

The team then combined these hydrogel electrodes with a pulse sensor to create an eye mask that can track eye movements and collect cardiac signals from the artery located at the brow bone. "Our team was able to really address that core problem to create a garment that you would be willing to wear and give you clinically accurate results when you use it," says Andrew. The research team, composed of Iranian, Indian American, Armenian-Greek, and Chinese American scientists named the eyewear Chesma, a word meaning eyeglasses or eyes in many of their languages.

One clinical use of the mask might be to monitor sleep. "One of the biggest classifiers between sleep stages is how radically you move your eyes," says Andrew. "We could correlate some of these sleep stages and also start to understand whether you have sleep disorder problems or if you have some underlying heart rate issues."

Besides performing as well as the adhesive clinical electrodes currently in use, the hydrogel electrodes used in Chesma are also extremely durable. The hydrogel can resist long-term build-up from makeup, pollution, and skin waste that may fault the electrodes, as well as withstand 15 laundry cycles. And the researchers found that Chesma's signal did not display any degradation after 6 hours of continuous use without rehydrating the hydrogel, suggesting that it could be worn for long periods of time. In fact, the hydrogel retains water so well that it takes almost 40 hours to dry out completely--and even if it does, Andrew says simply "a couple of drops of water on it, let it sit for about 30 seconds, and it becomes like gelatin once more."

Next, the research team wants to reduce the power demand of the device, which would allow users to charge the device once every three nights instead of every 8 hours. The extended battery life can also facilitate potential applications during people's waking hours. Besides its potential uses in health monitoring, the team would also like to see it deployed in other fields such as virtual reality and gaming or advertisement performance analysis, where it could help researchers understand if an ad literally "caught people's eye."

Credit: 
Cell Press

Black/white disparity in lung cancer incidence reversed or eliminated among young adults

A trend of higher lung cancer incidence rates in young Black people versus young white people in the United States has flipped, with the Black/white gap disappearing in men and reversing in women. The changing trends coincide with steeper declines in smoking in Black Americans, according to a new study, which appears in JNCI Cancer Spectrum.

Lung cancer is the leading cause of cancer death in the United States, with about 80% of the total 154,000 deaths recorded each year caused by cigarette smoking. Historically, lung cancer incidence rates have been higher in non-Hispanic Black people than non-Hispanic white people among men of all ages and among younger women, likely reflecting historically higher smoking rates in Black adults.

For the new study, American Cancer Society investigators led by Ahmedin Jemal DVM, PhD, examined smoking prevalence data and national lung cancer incidence rates for Black and white people by sex among contemporary young birth cohorts, to investigate whether incidence patterns are consistent with race- and sex-specific smoking patterns.

They found incidence decreased in both Black and white men born since about 1947 and in women born since abut 1957, with the declines steeper in Black people than white people. Those steeper declines led to the Black/white gap disappearing in men born in 1967 to 1972 and reversing in women born since about 1967. Similarly, historically higher smoking rates in Black people versus white people disappeared in men and reversed in women born since about 1965.

There was one notable exception. The authors identified increasing lung cancer incidence rates in Black men born around 1977-1982, which indeed led to higher lung cancer incidence rates in Black than white men born during this period. "This increase likely reflects the steep rise in initiation of smoking among Black adolescents in 1990s, which coincided with the R.J. Reynold's tobacco advertisement campaign targeting African Americans," write the authors. "Between 1991 and 1997, the prevalence of current cigarette use among Black high school students doubled from 14.1% to 28.2%."

The authors say that their findings have significant public health implications. "Our study reflects the success of national, state, and local anti-tobacco public health policies and activities in the Black community despite the tobacco companies' targeted and deceptive marketing strategies," said Dr. Jemal. "At the same time, the increase in lung cancer incidence among Black men born around 1982 reflects the lack of strong public health policies to prevent the rise in smoking initiation in 1990s."

"While these patterns herald progress in reducing racial disparities in lung cancer occurrence and the success of tobacco control in the Black community, the increasing lung cancer incidence rates in Black men born circa 1977-1982 is concerning and underscores the need for targeted tobacco prevention interventions," the authors conclude.

Credit: 
American Cancer Society

Robotic surgery may improve outcomes in mouth and throat cancer

image: A Cedars-Sinai surgical team conducts a robotic surgery.

Image: 
Cedars-Sinai

LOS ANGELES (Aug. 20, 2020) - Robotic surgery for patients with early stage, oropharyngeal squamous cell cancer is associated with improved health outcomes, including better long-term survival, according to a Cedars-Sinai study published Thursday in JAMA Oncology. Oropharyngeal cancer occurs in the back of the throat and includes the base of the tongue and tonsils. ­­

Transoral robotic surgery is a minimally invasive procedure in which a surgeon uses a computer-enhanced system to guide an endoscope - a flexible tube with a light and camera attached to it - to provide high-resolution, 3D images of the back of the mouth and throat, an area that is difficult to reach with conventional tools. Two robotically guided instruments, acting as a surgeon's arms, work around corners to safely remove tumors from surrounding tissue.

The Cedars-Sinai retrospective, observational study, which used data from the National Cancer Database, included 9,745 surgical patients - 2,694 of whom underwent transoral robotic surgery between 2010 and 2015. The authors found that the five-year overall survival rate for patients with early-stage disease who underwent robotic surgery was 84.5%, compared with 80.3% for patients who had non-robotic surgery, after adjusting for differences in health and other characteristics of the two patient groups.

"At a minimum, robotic surgery for oropharyngeal cancer patients seems safe and effective compared to what's been the standard of care for many years," said Zachary S. Zumsteg, MD, assistant professor of Radiation Oncology at Cedars-Sinai, referring to standard surgery, radiation therapy and chemotherapy. He is the study's senior and corresponding author. Anthony T. Nguyen, MD, PhD, a resident in the Department of Radiation Oncology at Cedars-Sinai, is the study's lead author.

Oropharyngeal cancer often is associated with the human papilloma virus, which is believed to cause 70% of oropharyngeal cancers in the United States, according to the Centers for Disease Control and Prevention. About 3,500 new cases of HPV-associated oropharyngeal cancers are diagnosed in women and about 15,500 in men each year in the U.S.

The Cedars-Sinai study observed that the proportion of patients undergoing transoral robotic surgery for early-stage oropharyngeal cancer increased dramatically after the U.S. Food and Drug Administration approved the surgery for that cancer in 2009 - from 18.3% in 2010 to 35.5% in 2015, according to the researchers' findings. Additionally, the proportion of facilities performing transoral robotic surgery during that same period more than doubled, from 6.3% to 13.9%.

The nationwide increase in transoral robotic surgery for oropharyngeal cancer prompted the investigators to assess whether the theoretical benefits of robotic surgery for oropharyngeal cancer patients actually provide outcomes that are superior or equivalent to the standard treatments for that cancer type and others.

In addition to increased overall survival rates, the researchers found that robotic surgery was associated with lower rates of positive surgical margins - 12.5% - compared with a rate of 20.3% for non-robotic surgery in patients with oropharyngeal cancer. Positive surgical margins refer to cancer cells that remain at the edge of tissue that has been surgically removed. Furthermore, robotic surgery was associated with less use of postoperative chemoradiation, at 28.6%, compared with 35.7% for patients who had non-robotic surgery.

"Our purpose in doing this study was to see how this new technology, which has never been tested in a randomized, controlled trial, has influenced patterns of treatment and outcomes since its FDA approval," Zumsteg said. "There is a learning curve with any new surgical technique, and new ones don't always translate into equal or improved outcomes."

Referring to their study results as "hypothesis-generating," the researchers hope it will inform future randomized, controlled clinical trials," Nguyen said.

"Meanwhile, it's reassuring to our patients that their survival rate is the same if not better with robotic surgery and they have the potential for a better quality of life," Nguyen said.

Credit: 
Cedars-Sinai Medical Center

Larger variability in sea level expected as Earth warms

image: Waves crash on the Waikiki shoreline of O'ahu, Hawaii during a high tide.

Image: 
Hawaii Sea Grant King Tides Project, 2017. Creative Commons Attribution 4.0 International License (CC BY 4.0).

A team of researchers from the University of Hawai'i (UH) at Mānoa School of Ocean and Earth Science and Technology (SOEST) identified a global tendency for future sea levels to become more variable as oceans warm this century due to increasing greenhouse gas emissions. Sea level variability alters tidal cycles and enhances the risks of coastal flooding and erosion beyond changes associated with sea level rise.

Sea level rise is occurring as Earth warms due to two main factors: melting of land-based ice such as glaciers and ice sheets, and the expansion of seawater as it warms - termed thermal expansion. Previously unknown was whether the rate of thermal expansion, which accelerates with warming, will also affect the variability of sea level.

In a study published this week in Communications Earth & Environment, the team led by Matthew Widlansky, associate director of the UH Sea Level Center, assessed future sea level projections from global climate models. The team found that while future sea level variability changes are uncertain in many locations, nearly all of the 29 models they analyzed agreed on an overall tendency for the variability to increase on seasonal-to-interannual timescales.

"Whereas it is well understood that the rate of global mean sea level rise will accelerate with future warming, in part due to the oceans expanding faster at higher temperatures, it was previously unexplored how this nonlinear thermal expansion property of seawater will affect future sea level variability," said Widlansky.

"Following thermodynamic laws, sea level variability increases in a warmer climate because the same temperature variations, for example related to the seasonal cycle, cause larger buoyancy and sea level fluctuations," added Fabian Schloesser, a researcher at the UH Sea Level Center who collaborated on the study.

In places where changes due to ocean thermodynamics and other climate variability processes align, the team found the largest increases in future sea level variability.

Coastal flooding occurs increasingly often due to a combination of slowly rising sea levels and ocean variability. The new findings therefore further emphasize the importance of sea level monitoring and forecasting.

"Forecasting can potentially provide alerts months in advance if sea levels are likely to cause tides to be more extreme than otherwise expected," said Widlansky.

While the science team explores how to develop better forecast outlooks, the UH Sea Level Center is actively monitoring extremes through a global network of tide gauge observations, including in Honolulu, Hawai'i.

Credit: 
University of Hawaii at Manoa

UMass Amherst scientists invent new sensing eye mask

image: Announcing a soft new wearable eye mask for use in sleep and other studies, lead author Trisha Andrew at UMass Amherst says that recording health and behavior signals on or near the face is challenging because most people are really sensitive and reactive to objects placed on their face or head.

Image: 
UMass Amherst/Andrew lab

AMHERST, Mass. - From the team that invented physiology-sensing pajamas at the University of Massachusetts Amherst, now comes a new, lightweight eye mask that can unobtrusively capture pulse, eye movement and sleep signals, for example, when worn in an everyday environment.

Senior authors writing this week in the journal Matter are materials chemist and Wearable Electronics Lab director Trisha L. Andrew, with computer scientist Deepak Ganesan and others. They point out that "being able to track pulse and eye movement in a single wearable device will enable a host of sleep and psycho-social studies, in addition to improving the accuracy and usability of gaming and virtual reality headsets." First author
S. Zohreh Homayounfar, will present the findings this week at the online Fall Meeting of the American Chemical Society.

Recording health and behavior signals on or near the face is challenging, notes Andrew, "because most people are really sensitive and reactive to objects placed on their face or head." Ganesan adds that "up to now, integrating many different sensing elements in one garment seemed burdensome, especially when it comes to small eye masks."

They say their lightweight, tailorable eye mask named "Chesma," is fitted with two kinds of fabric electrodes that can simply be sewn onto a variety of pre-made garments and further miniaturized, if desired. This capability allows them to integrate electrodes into a lightweight foam mask for recording electro-oculography and cardiac signals. Their design automatically positions the electrodes on the face with no need for custom fitting.

As explained in a video created by Ph.D. student and first author, S. Zohreh Homayounfar, the mask contains five silver (Ag) thread-based hydrogel electrodes -dubbed tAgTrodes - needed to translate ion-based biological signals into an electric current, among other goals. The researchers took advantage of a vapor-phase deposition process to create the electrodes, including what they call a first-of-its-kind reusable and washable hydrogel component that distinguishes the tAgTrode from other equivalents.

Here, Andrew says she takes pride in noting that "part of the work that went into carrying out the deposition process was performed by Emerson T. Alexander, an exceptional student from Springfield Technical Community College," who took part in a paid internship in her lab and funded by the L'Oréal USA For Women in Science program.

The mask also contains one fabric pressure sensor (PressION) positioned over an artery to monitor pulse as a proxy for cardiac function, with the whole linked to two microcontrollers with water-repellant silver threads as connectors. Another author, Ph.D. student Ali Kiaghadi, explains that "the electrode and sensor data need to be communicated once they are acquired. Our design transmits raw data to the cloud for processing and data visualization, so that we can reduce the amount of instrumentation that we need to include in the mask itself."

The team tested the new eye mask on subjects while they were chewing, talking, and during various head and eye movements. They also used the same device for more than a year and after 15 washings found no degradation in performance. Homayounfar notes that the tAgTrode "overcomes all the drawbacks of commercial wet electrodes such as aesthetic issues, discomfort and wash-stability, while maintaining high and constant signal-to-noise ratios during repeated, longterm applications."

Andrew expects that Chesma's "unique bimodality" - the combination of electrode network with the pressure sensor - will enable many new cutting-edge studies not possible until now, for investigating sleep quality, sleep disorders, mental health, neurodegenerative diseases and schizophrenia, for example.

Credit: 
University of Massachusetts Amherst

University of Louisville immunologist summarizes functions of protein family for scientific community

image: SnapShot created by Bing Li, Ph.D., to illustrate the functions of fatty acid binding proteins (FABPs)

Image: 
Cell

LOUISVILLE, Ky. - Fatty acid binding proteins (FABPs) serve as a type of chaperone, coordinating the transport of fatty acids and other molecules between cells. Bing Li, Ph.D., associate professor in the Department of Microbiology and Immunology at the University of Louisville and a leading researcher in understanding the role of FABPs, has created a "SnapShot" of the functions of these proteins published in the journal Cell, a highly regarded scientific journal covering cell biology.

At least nine types of FABPs, identified by the tissues and organs in which they were first discovered, are known to have numerous roles in lipid metabolism. While they are responsible for important functions in maintaining health, obesity can result in higher levels of these proteins, igniting disease.

"When people are obese, FABPs in different cells and tissues are upregulated, resulting in changes in lipid metabolism and responses," Li said.

Li's research focuses the role of FABPs in chronic inflammation, obesity and cancer development. He recently published a proposed mechanism for how increased levels of one of these proteins, FABP4, resulting from higher amounts of fat tissue, promote breast tumor growth.

"Studies from my laboratory demonstrate that FABP family members, especially FABP4 and FABP5, are critical in mediating obesity-associated diseases by regulating immune cell functions," Li said. "Thus, our studies on FABPs not only uncover the underlying mechanisms by which obesity undermines human health, but also provide new targets for novel immunotherapeutic strategies for clinics."

Editors of the journal Cell invited Li to create the SnapShot to illustrate the functions of all known FABPs in health and disease with an emphasis on their role in obesity, chronic inflammatory disease and cancer. SnapShots are graphic diagrams designed to serve as quick reference guides for researchers on a specific topic.

"The SnapShot format offers a great deal of opportunity for creativity and can be printed and pinned above lab benches to jog researchers' memories," Li said. "While our studies open a window to see the important functions of FABP family members in some disease contexts, a lot of questions remain unexplored in this field. I hope this piece will encourage more young scientists to contribute their talents to combat obesity and obesity-associated diseases."

Credit: 
University of Louisville

Lipid-Oligonucleotides (LONs) --- Promising materials for bioapplications

image: Schematic illustrations of some bioanalytical applications of LONs. (A) A reversible cell membrane-anchored K+ probe. Copyright (2016) Royal Society of Chemistry. (B) (C) Cell membrane-immobilized DNA tweezers for monitoring extracellular pH. Copyright (2018) American Chemical Society. (D) T cell-aptamer sensor for measuring cytokine secretion. Copyright (2017) Royal Society of Chemistry.

Image: 
Copyright (2017) Royal Society of Chemistry

Lipids are very essential components in composing living systems and are important for cell signaling and nutrient transport. Meanwhile, lipids have been widely used as carriers in many anticancer drugs development because of their capability in increasing solubilization and improving pharmacokinetics of drugs. Based on this, lipid-oligonucleotides (LONs), the new molecular materials have been designed and have shown outstanding properties in different molecular designs for applications from bioanalysis and biosensing to biomedical technologies.

Due to the information-transfer and self-assembly abilities of the two segments, LONs have presented advantages in designing membrane-anchored biosensors and synthetic membrane channels. For example, LONs have been used in the researches of cell membrane anchored sensors for monitoring extracellular molecules and measuring biophysical events on the live cell surface, because of the similarity between the lipid part of LONs and lipid bilayers in cell membrane. Moreover, LONs have great potential in making contributions to developing new therapies and controllable nanoreactors by designing different structures with tunable compositions of two moieties.

Recently, Professor Weihong Tan lead a group of researchers, including Dr. Xiaowei Li, et al. from University of Florida and Dr. Kejun Feng from Huizhou University reported a systematic review discussing this powerful molecular engineering material, LON, and its wide applications from biosensors to biomedicine.

They first summarized the current general synthesis strategies of preparing LONs (pre- and post-synthetic approaches), describing their basic structures and some related characterization analysis of properties, suggesting that LONs have unique recognition ability and excellent stability, which are the prerequisites for biomedical and analytical applications. The special amphiphilic structures of LONs also provide themselves enhancing drug encapsulation and targeted recognition abilities, benefiting the downstream applications.

Then, the researchers discussed the recent advances in applying LONs in various areas. LONs could be modified to build cell membrane anchored biosensors, targeted cancer therapeutics or imaging probes, as well as programmable nanoreactors, indicating that LONs are super versatile materials and could favor different purposes. At the same time, the current challenges and future directions of improving LONs were also mentioned in the review, which may help guide the better developments of LONs-based materials for more biological applications.

Credit: 
Science China Press

An active lifestyle reduces fearfulness in dogs - differences between breeds are great

Noise sensitivity, fear of novel situations and, for example, fear of slippery surfaces and heights are common behavioural problems among dogs. According to a behavioural survey of nearly 14,000 dogs conducted at the University of Helsinki, these non-social fears are associated with factors related to the dogs' living environment, lifestyle and breed.

Dogs that were engaged in activities the most and were actively trained were found to be the least fearful.

"Physical exercise has been shown to have a positive effect on the mood in both dogs and humans. As social animals, dogs enjoy doing things with their owners. At the same time, people do not necessarily wish to subject fearful dogs to training situations that are stressful for them. This can also make owners less inclined to train with their dog," says doctoral student Emma Hakanen from the Faculty of Medicine, University of Helsinki.

The survey indicates that insufficient socialisation of puppies to various situations and new environments in particular has a strong link with fearfulness related to novel situations, loud noises as well as different walking surfaces, such as slippery surfaces, transparent stairs or metal grilles. On the other hand, the company of other dogs reduced the occurrence of non-social fear.

Fear of fireworks and surfaces was more prevalent among the dogs of first-time dog owners, while differences were also seen between rural and urban dogs.

"Our prior research on the environmental effects of social fear observed the same phenomena where urban dogs were more fearful than their rural counterparts. Indeed, it is interesting that human mental health problems too occur more frequently in the city than in rural areas. The ways in which our environment shapes us and our best friend is definitely an interesting topic for further research," says Professor Hannes Lohi from the Faculty of Veterinary Medicine and Faculty of Medicine, University of Helsinki.

Furthermore, as suggested by prior research, the study demonstrated that non-social fearfulness also is more common in sterilised females and small dogs. Being fearful of slippery or otherwise unfamiliar surfaces was also associated with a generally fearful disposition in dogs.

Significant differences between breeds were identified in the study, with Cairn Terriers among the most fearful breeds and Chinese Crested Dogs among the least fearful.

However, variance was seen between different non-social fears in the fearfulness of individual breeds. For instance, Welsh Corgi Pembrokes expressed a lot of noise sensitivity but little fearfulness of surfaces. At the same time, the latter was common among Lapponian Herders, Miniature Schnauzers, Chihuahuas and Labrador Retrievers, while noise sensitivity was less so.

"The breed-specific differences support the idea that fearfulness is inherited. In other words, breeding choices matter, even without knowing the exact mechanisms of inheritance. However, this study offers dog owners tools and support for previous notions related to improving the wellbeing of their dogs. Diverse socialisation in puppyhood and an active lifestyle can significantly reduce social and non-social fearfulness," Lohi sums up.

The study is part of Professor Lohi's wider Academy of Finland project, which investigates the epidemiology of canine behaviour, as well as related environmental and genetic factors and metabolic changes.

Credit: 
University of Helsinki