Culture

WACO, Texas (July 13, 2021) - Climate change mitigation efforts have led to shifts from fossil-fuel dependence to large-scale renewable energy. However, renewable energy sources require significant land and could come at a cost to ecosystems. A new study led by Ryan McManamay, Ph.D., assistant professor of environmental science at Baylor University, evaluates potential conflicts between alternative energy strategies and biodiversity conservation.

The study, published in Biological Conservation, evaluates potential tradeoffs between climate benefits and energy costs, especially any negative impacts on biodiversity. While the environmental consequences of some renewable energy sources, like hydropower, have been widely studied, the large-scale impacts of other renewables, like solar, aren't well known.

"The study points to a need for the global community to understand the opposing endpoints of sustainability, which are scale-dependent," McManamay said. "At one endpoint, efforts to mitigate climate change at global scales via large-scale energy transitions may be completely incognizant of the consequences on local biodiversity. Likewise, local conservationists may not appreciate the magnitude of energy transitions required to shift global carbon emissions. Finally, I think there is a broad misconception among much of the community that if renewable energies are good for climate, they must also be good for the local ecosystem. Energies like solar have the potential to be deployed haphazardly with that mindset."

The challenges of climate mitigation in relation to different climate policy scenarios are projected in five Shared Socio-economic Pathways (SSPs) -- qualitative descriptions of plausible alternative socio-economic development in the next century. The SSPs include alternative projections in deployment of electricity generations by technology. Considering scenarios under the SSPs, ecological footprinting was used to evaluate the potential land and biodiversity tradeoffs of 10 different energy sources: solar photovoltaic, concentrated solar power, wind, hydropower, coal, conventional oil, conventional gas, unconventional oil, unconventional gas, and biomass.

"Ecological footprinting took into account land-use efficiencies of each technology as well as estimates of the degree of habitat alteration arising from technology deployment," McManamay said. "This provides a standardized way to compare the biodiversity consequences of large-scale deployment of alternative energy technologies."

Researchers estimated a biodiversity footprint for each of the 10 energy sources by overlaying energy densities and habitat alteration probabilities with biodiversity patterns. They then used spatial modeling to examine regional variations in future energy deployment and potential biodiversity impacts at a high-resolution. Different biodiversity footprints were scored based on their impact and a cumulative biodiversity score was determined for each of the 10 energy sources.

The cumulative impact scores among the SSPs showed significant and consistent differences -- the fossil-fueled development pathway (SSP 5) had the highest impacts while the regional rivalry scenario (SSP3) had the lowest. The sustainability-focused scenario (SSP1) represented a moderate impact score by comparison. Unexpectedly, the variation among SSPs didn't show a clear tradeoff between global climate mitigation and cumulative biodiversity impact.

"It was surprising to see the lack of a clear tradeoffs among sustainability endpoints," McManamay said. "This elicited us to take a deeper look into differences among the SSPs. Although SSP5 is termed 'fossil-fueled' development, the pathway includes significant technological advances in both advanced fossil and renewable technologies to meet highly consumptive, energy-luxurious lifestyles. In other words, the biodiversity impacts are more related to total energy deployment than fossil versus renewable technologies. Although SSP1 is also characterized by significant renewable energy deployment, overall energy demand decreases due to increases in energy efficiencies. So, our work suggests that climate mitigation may not necessarily have to be at odds with biodiversity conservation."

Additionally, land constraints accounted for the most variation in biodiversity impact, particularly with regard to protected land use. Downscaled electricity generation scenarios were constrained by alternative land conservation and energy development policies.

The results offer an approximation of land and biodiversity impacts of future energy strategies outlined in the SSPs. While there were differences in the SSPs, the impact scores suggest that land protection measures and energy diversification could have greater implications for biodiversity challenges than the national-level global energy pathways outlined in the SSPs. Future planning and objectives for climate mitigation will require both broad and local consideration of biodiversity challenges.

An important new study by researchers at the U.S. Department of Energy’s (DOE) Argonne National Laboratory has yielded critical fresh insights into the lithium production process and how it relates to long-term environmental sustainability, particularly in the area of transportation with batteries and electric vehicles.

The paper, “Energy, Greenhouse Gas, and Water Life Cycle Analysis of Lithium Carbonate and Lithium Hydroxide Monohydrate from Brine and Ore Resources and Their Use in Lithium Ion Battery Cathodes and Lithium Ion Batteries,” in the journal Resources, Conservation & Recycling, was the result of a unique collaboration with SQM, a Chilean company that is one of the world’s biggest producers of lithium.

According to Argonne lifecycle analyst and lead author Jarod Kelly, the researchers — using operational data supplied by SQM — found that the sourcing of lithium, from both a process and location perspective, can strongly affect its associated environmental impacts.

“The results show that concentrated lithium brine and its related end products can vary significantly in energy consumption, greenhouse gas emissions, sulfur dioxide emissions and water consumption depending upon the resource allocation method used,” Kelly explained.

The researchers modeled brine-based lithium extracted from the Salar de Atacama, a large salt flat in northern Chile near the Andes Mountains. The lithium is naturally dried in large ponds to evaporate the water, concentrate the lithium, and remove impurities. Materials and energy are later added to produce lithium carbonate and lithium hydroxide. These two end products are shipped worldwide to battery cathode producers that process them into a variety of battery materials.

The study findings could have major implications for how to optimize lithium production at each stage of the process, which would result in more environmentally-friendly products, particularly battery electric vehicles. The International Energy Agency predicts that demand for lithium may grow by as much as 40 times between 2020 and 2040, mainly due to global deployment of electric vehicles.

“Examination of current lithium production and the pursuit of future production, including from within the U.S., are critical to sustaining electric vehicle deployment,” said Michael Wang, director of the Systems Assessment Center at Argonne and a study co-author.

“This study establishes a baseline for current practices and shows us potential areas for improvement,” added Kelly. “With further research, it will be possible to use this information to help develop best practices for producing lithium in the most sustainable way.”

SQM initially approached Argonne last year about a collaboration in support of ambitious sustainability targets the company recently unveiled.

“According to our sustainability plan, we want to look more closely at carbon emissions, water consumption and energy consumption in our lithium products, and see how it affects the rest of the value chain,” said Veronica Gautier, SQM’s head of innovation. “This information will help us achieve our goal of being carbon neutral by 2030.”

The analysis will also help address an overarching question in the global trend toward the electrification of transportation with battery electric vehicles, Wang said.

“Often electrification is for the purpose of pursuing environmental sustainability. But we need to know more about lithium battery production before we can say we are truly on a sustainable path,” he said. “This study provides crucial insights into the electric mobility value chain.”

The formal analysis used Argonne’s open-source modeling tool, GREET (Greenhouse gases Regulated Emissions and Energy in Technologies), with detailed data and technical insight coming from SQM. In addition to the brine-based lithium extracted in Chile, the researchers augmented their data by modeling ore-based lithium extracted from spodumene ore in Western Australia.

Kelly said it was the first analysis of its kind to be based on such comprehensive data from an industrial partner. Gautier added that SQM was pleased that the study results were now publicly available and would help further global efforts toward ensuring responsible and sustainable lithium production.

“It is important for us to have full and complete transparency about how our process works, and we’re excited to leverage Argonne’s experience and expertise,” she said. “Sharing this information will have great educational value.”

Osaka, Japan - When things get too much, we're often advised to "take a load off," but when it comes to bone maintenance, doing the opposite can be a good thing. Researchers from Japan have discovered some key mechanisms of how physical load stimulates bone growth.

In a study published July 13, 2021 at 11 a.m. ET in Cell Reports, researchers from the National Cerebral and Cardiovascular Center Research Institute have revealed that the expression of the peptide osteocrin (OSTN) is influenced by load - decreasing when load is reduced, and increasing when it is added.

Bones and skeletal muscles are strengthened by the load associated with exercise, preventing bone and muscle atrophy, and maintaining bone and muscle strength is important for maintaining physical activity. The growth of long bones, such as the femur and tibia, is a very complex process controlled by genetic and environmental factors, such as exercise and gravity.

"Not much is known about how mechanical force initiates biochemical signals to control bone growth," says lead author of the study Haruko Watanabe-Takano. "We investigated how load is related to the metabolic balance adjustment of bone maintenance."

Bone is maintained by the balanced activities of two types of cells - osteoblasts, which make bone, and osteoclasts, which break down bone - and is thought to be made in response load demand. Specifically, the team investigated the expression of OSTN, a peptide produced by osteoblasts, in mice. OSTN is critical to the regulation of bone growth, as well as physical endurance.

The researchers found that OSTN was very strongly expressed in bones such as the tibia, radius, and ulna, and in the region where the load was applied. Additionally, they showed that OSTN was secreted by the periosteal osteoblasts in these bones. The periosteum is a membrane found on the outer surface of bones, except at the joints of long bones, and is involved in bone remodeling and production, especially during growth.

"We also found that OSTN expression decreased when load was reduced, and was increased by load stimulation," says Watanabe-Takano. "Moreover, when we genetically engineered mice lacking OSTN, we found that they had reduced bone mass compared with normal mice and lacked load-induced recovery of bone mass after prolonged load reduction. Thus, we concluded that OSTN makes bone in response to stimulation by load, promoting bone formation."

When they looked into how OSTN might achieve this effect, the team found that it increases levels of another peptide, called C natriuretic peptide, which in turn drives bone-forming osteoblasts to multiply, mature, and become functional.

The results of this study will be useful for the promotion of bone maintenance in bedridden patients, because bone formation is known to be inhibited by long-term bed rest, and for the prevention and treatment of frailty syndrome. Future studies will build on these results to discover further mechanisms, such as how periosteal cells detect load stimulation.

An associate professor of marketing at The University of Texas at Arlington says digital avatars can replace a sales force and customer service employees at a fraction of the cost.

In this context, avatars are typically computer-generated representations of people. UTA Associate Professor Fred Miao says they can fill the void in interactive assistance that a majority of shoppers says they want.

"An Accenture survey of online shoppers shows that 62% never completed their purchases because there was no real-time customer service or support. That Accenture survey also shows that 90% of those shoppers wanted some sort of interactive assistance during the shopping process," said Miao, faculty fellow of the John Merrill Endowed Professorship in Consultative Sales in UTA's College of Business. "Avatars, used in the right way, can fill this void at a fraction of the cost of hiring and training human salespeople and service employees."

Miao's paper, "An Emerging Theory of Avatar Marketing," appears in the Journal of Marketing, the premier research outlet for the American Marketing Association.

In his analysis, Miao argues that businesses using avatar representatives need to be on the lookout for misalignment between the form and behavioral realism of their avatars. Form realism relates to how much an avatar looks like a real human being. Behavioral realism relates to an avatar's "intelligence" and whether it acts like a human being.

"Getting those two parts of an avatar matched is difficult," Miao said. "When the physical and the behavioral aspects don't synch up, the effectiveness of using avatars can be inconsistent and at best contingent upon the context, such as perceived financial risk."

In complex relational exchanges with customers, such as when someone chooses a skincare product, avatars may be most effective when they are highly realistic looking and intelligent. When interactions involve privacy concerns, such as in mental health interviews, customers are better served with less realistic looking avatars that still act with intelligence.

Miao urges firms to consider five interrelated areas in using avatars:

timing

form realism

behavioral realism

form-behavioral realism alignment

situational factors and context

"The bottom line is that with budgets being so constricted among businesses, using avatars for marketing or customer service could not only be a worthwhile management tool to consider using, but also a means of increasing sales through consistent service quality," Miao said.

Elten Briggs, chair and associate professor in the Department of Marketing, said Miao's work conveys critical insights to businesses.

"Avatars and other forms of artificial intelligence are increasingly being employed to deliver services to customers," Briggs said. "Dr. Miao's paper provides much needed guidance on how businesses can utilize avatars to improve customers' service experiences."

UW researchers reveal new aspects of gum disease and body's protective response

SEATTLE - A team led by University of Washington researchers has, for the first time, identified and classified how different people respond to the accumulation of dental plaque, the sticky biofilm that gathers on teeth. Their work, recently published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS), sheds important new light on why some people may be more prone to serious conditions that lead to tooth loss and other problems.

Left unchecked, plaque buildup can induce gingivitis, or gum inflammation. Gingivitis, in turn, can lead to periodontitis, a serious gum infection that damages the soft tissue and can destroy the bone that supports teeth. Not only can this result in tooth loss, but chronic inflammation can also spur other serious health consequences, including heart disease, diabetes, cancer, arthritis, and bowel diseases.

The researchers also found a previously unidentified range of inflammatory responses to bacterial accumulation in the mouth. When bacteria build up on tooth surfaces, it generates inflammation, a tool the body uses to tamp down the buildup. Previously, there were two known major oral inflammation phenotypes, or individual traits: a high or strong clinical response and a low clinical response. The team identified a third phenotype, which they called "slow": a delayed strong inflammatory response in the wake of the bacterial buildup.

The study revealed for the first time that subjects with low clinical response also demonstrated a low inflammatory response for a wide variety of inflammation signals. "Indeed, this study has revealed a heterogeneity in the inflammatory response to bacterial accumulation that has not been described previously," said Dr. Richard Darveau of the UW School of Dentistry, one of the study's authors.

His School of Dentistry colleague and study co-author Dr. Jeffrey McLean said, "We found a particular group of people that have a slower development of plaque as well as a distinct microbial community makeup prior to the start of the study." The study authors wrote that understanding the variations in gum inflammation could help better identify people at elevated risk of periodontitis. In addition, it is possible that this variation in the inflammatory response among the human population may be related to susceptibility to other chronic bacterial-associated inflammatory conditions such as inflammatory bowel disease.

In addition, the researchers found a novel protective response by the body, triggered by plaque accumulation, that can save tissue and bone during inflammation. This mechanism, which was apparent among all three phenotypes, utilizes white blood cells known as neutrophils. In the mouth, they act something like cops on the beat, patrolling and regulating the bacterial population to maintain a stable condition known as healthy homeostasis.

In this instance, plaque is not a villain. To the contrary, the researchers said that the proper amount and makeup of plaque supports normal tissue function. Studies in mice have also shown that plaque also provides a pathway for neutrophils to migrate from the bloodstream through the gum tissue and into the crevice between the teeth and gums.

When healthy homeostasis exists and everything is working right, the neutrophils promote colonization resistance, a low-level protective inflammatory response that helps the mouth fend off an excess of unhealthy bacteria and resist infection. At the same time, the neutrophils help ensure the proper microbial composition for normal periodontal bone and tissue function.

The researchers' findings underscore why dentists preach the virtues of regular brushing and flossing, which prevent too much plaque buildup. "The idea of oral hygiene is to in fact recolonize the tooth surface with appropriate bacteria that participate with the host inflammatory response to keep unwanted bacteria out," Dr. Darveau said. The bacteria start repopulating the mouth's surfaces spontaneously and almost immediately afterward, he said.

DALLAS, July 12, 2021 -- People of South Asian ancestry have more than double the risk of developing heart disease compared to people of European ancestry, yet clinical risk assessment calculators used to guide decisions about preventing or treating heart disease may fail to account for the increased risk, according to new research published today in the American Heart Association's flagship journal Circulation.

About a quarter of the world's population (1.8 billion people) are of South Asian descent, and prior research has shown South Asians experience higher rates of heart disease compared to people of most other ethnicities.

To better understand the variables surrounding the heart disease risk for people of South Asian ancestry, researchers evaluated data from a subset of participants in the UK Biobank study who did not have atherosclerotic cardiovascular disease when they enrolled in the study between 2006 and 2010. There were 8,124 participants of South Asian Ancestry and 449,349 of European ancestry included in this analysis. Their average age was 57 and they were followed an average of 11 years. People in the South Asian ancestry group were defined as those who self-reported being of Indian, Pakistani or Bangladeshi origin, or who reported other South Asian heritage, such as their country of birth as Bhutan, Maldives, Nepal or Sri Lanka. European ancestry was based on self-identification as being white British, white Irish, or any other white European background.

Researchers compared the rates of developing cardiovascular disease (heart attack, stroke, or a procedure to restore normal blood supply to the heart) among people of South Asian ancestry to the rate among people of European ancestry.

They found that 6.8% of participants of South Asian ancestry had a cardiovascular disease event, compared to 4.4% of those who reported having European ancestry. After adjustment for age and sex, this represents a more than two-fold higher risk for people of South Asian descent. The higher relative risk was largely consistent across a variety of age, sex and clinical subgroups. However, this increased risk was not captured by the clinical estimators used in the United States or Europe.

"Based on previous studies, we expected South Asians would have higher rates of heart disease - in fact, the American Heart Association now considers South Asian ethnicity a 'risk enhancer' beyond the standard risk calculator," said senior study author Amit V. Khera, M.D., M.Sc., a cardiologist in the Corrigan Minehan Heart Center and leader of a research group within the Center for Genomic Medicine, both at Massachusetts General Hospital in Boston.

"We were surprised by the magnitude of the increased risk -- even within contemporary clinical practice, it was more than double -- and how much of it remains unexplained by traditional clinical or lifestyle risk factors," he said. "Our current tools do not help us predict this extra risk in the South Asian population, likely because no South Asians were included in developing the U.S. tool, so we may be missing opportunities to prevent heart attacks and strokes in this group. Intensive control of risk factors like high cholesterol and Type 2 diabetes are even more important in this population."

A higher percentage of people in the South Asian study group did have more risk factors for heart disease, including Type 2 diabetes (even in the absence of obesity), high blood pressure and increased central adiposity (belly fat). However, even when researchers accounted for the known risks, the risk for people of South Asian ancestry was still 45% higher than for people of European ancestry.

"We need to dig deeper to better understand why South Asians are having heart attacks and strokes at higher rates even after accounting for these risk factors," said Aniruddh P. Patel, M.D., lead author of the study and a cardiology fellow at Massachusetts General Hospital. "Our ability to study South Asian and other populations in general in the United States using public databases has been limited because individuals are grouped together by race rather than ancestry. This makes recognizing and addressing these disparities among a fast-growing South Asian population in the U.S. more difficult. In addition to recruiting more South Asians in clinical trials and cohort studies, better reporting of ancestry in addition to race in hospital data systems and electronic medical records would help us better understand and target these disparities."

The research does have some limitations. The study included adults between the ages of 40 and 69 living in the United Kingdom, thus the results may not be generalizable to younger individuals or those who live in other countries. Additionally, based upon the data, people who volunteered for the UK Biobank study were known to be healthier compared to the general population, thus, there were potentially reduced rates of heart disease in both ancestry groups. Further, medical records of study participants were reviewed electronically rather than manually, so underreporting may have occurred.

Khera and colleagues have assembled a team of international investigators to aggregate data and expertise needed to develop new genetic risk estimators for South Asian individuals as part of an NIH-funded consortium. As for the clinical risk estimator tools, South Asians have been severely under-represented to-date, accounting for only about 1% of studied individuals.

A novel method of gene therapy is helping children born with a rare genetic disorder called AADC deficiency that causes severe physical and developmental disabilities. The study, led by researchers at The Ohio State University Wexner Medical Center and The Ohio State University College of Medicine, offers new hope to those living with incurable genetic and neurodegenerative diseases.

Research findings are published online in the journal Nature Communications.

This study describes the findings from the targeted delivery of gene therapy to midbrain to treat a rare deadly neurodevelopmental disorder in children with a neurogenetic disease, aromatic L-amino acid decarboxylase (AADC) deficiency characterized by deficient synthesis of dopamine and serotonin.

Only about 135 children worldwide are known to be missing the enzyme that produces dopamine in the central nervous system, which fuels pathways in the brain responsible for motor function and emotions. Without this enzyme, children lack muscle control, and are usually unable to speak, feed themselves or even hold up their head. They also suffer from seizure-like episodes called oculogyric crises that can last for hours.

"Remarkably, these episodes are the first symptom to disappear after gene therapy surgery, and they never return," said study co-author Dr. Krystof Bankiewicz, professor of neurological surgery at Ohio State College of Medicine who leads the Bankiewicz Lab. "In the months that follow, many patients experience life-changing improvements. Not only do they begin laughing and have improved mood, but many are able to begin speaking and even walking. They are making up for the time they lost during their abnormal development."

The directed gene therapy in seven children ages 4 to 9 who were infused with the viral vector resulted in dramatic improvement of symptoms, motor function and quality of life. Six children were treated at UCSF Benioff Children's Hospital in San Francisco and one at Ohio State Wexner Medical Center. This therapeutic modality promises to transform the treatment of AADC deficiency and other similar disorders of the brain in the future, Bankiewicz said.

During the gene therapy surgery, physicians infuse a benign virus programmed with specific DNA into precisely targeted areas of the brain. The infusion is delivered extremely slowly as surgeons monitor exactly how it spreads within the brain using real-time MRI imaging.

"Really, what we're doing is introducing a different code to the cell," said Dr. James "Brad" Elder, director of neurosurgical oncology at Ohio State Wexner Medical Center's Neurological Institute. "And we're watching the whole thing happen live. So we continuously repeat the MRI and we can see the infusion blossom within the desired nucleus."

Researchers believe this same method of gene therapy can be used to treat other genetic disorders as well as common neurodegenerative diseases, such as Parkinson's and Alzheimer's disease. Clinical trials are underway to test this procedure in others living with debilitating and incurable neurological conditions.

The directed gene therapy, in these patients, resulted in dramatic improvement of symptoms, motor function and quality of life. This therapeutic modality promises to transform the treatment of AADC deficiency and other similar disorders of the brain in the future.

USC researchers have achieved a better way to identify elusive DNA variants responsible for genetic changes affecting cell functions and diseases.

Using computational biology tools, scientists at the university's Dornsife College of Letters, Arts and Sciences studied "variable-number tandem repeats" (VNTR) in DNA. VNTRs are stretches of DNA made of a short pattern of nucleotides repeated over and over, like a plaid pattern shirt. Though they comprise but 3% of the human genome, the repetitive DNA governs how some genes are encoded and levels of proteins are produced in a cell, and account for most of the structural variation.

Current methods do not accurately detect the variations in genes in some repetitive sequences. The new method by the USC scientists can detect variants among different populations of people and how it they affect gene expression, which helps to discover links between VNTR variation and traits or disease.

"This type of repetitive DNA has been called 'dark matter' of the human genome because it has been difficult to sequence and analyze how it varies," said Mark Chaisson, assistant professor of quantitative and computational biology and corresponding author of the study. "We showed that variation in dark matter can have a substantial effect on cellular processes, so future studies may use this approach to understand the genetic basis of disease and ways to improve our health."

The study was published in Nature Communications on July 12

The study also says:

Variants in genetic codes are responsible for Huntington's disease, Lou Gehrig's disease (ALS), schizophrenia, diabetes and attention-deficit disorder, as previous research has shown.

While other tools, based on algorithms, have been developed to detect genetic variants, they provide incomplete information, especially for the VNTRs.

The new software tool the USC scientists developed derives from a repeat-pangenome graph, a data structure that encodes population diversity and repetitions of VNTR locations on a chromosome to identify more gene sequences with better accuracy.

Scientists have produced the first fine-detail molecular blueprints of a bacterial enzyme known as Lit, which is suspected to play a "stealthy" role in the progression of infection by reducing the immune response.

Blueprints such as these allow drug designers to uncover potential weaknesses in bacterial arsenals as they seek to develop new therapeutics that may help us win the war against antibiotic resistance.

The study, led by scientists from the School of Biochemistry and Immunology and the Trinity Biomedical Sciences Institute (TBSI) at Trinity College Dublin, has just been published by leading international journal Nature Communications.

Lipoproteins and their role in bacterial infection

Lipoproteins serve diverse functions in the bacterial cell. Some are essential for survival while some play an important role by engaging with the innate immune response of the host.

The growing list of enzymes responsible for building lipoproteins includes the recently discovered Lit (lipoprotein intramolecular transacylase), which creates a specific lipoprotein that "cools the immune response" - raising the likelihood that Lit enables the bacteria to gain a foothold in the host by stealth.

With a view to understanding how Lit functions at the molecular level, the Trinity-led team has just produced Lit's all-important, high-resolution crystal structure from Bacillus cereus - a common bacteria found in soil and food.

Combined with other analytical techniques, molecular dynamics simulations and quantum mechanics approaches, the team now has a detailed understanding of how it functions.

Professor Martin Caffrey, Fellow Emeritus (Trinity and TBSI), is the senior author of the research. Underlining its significance and potential societal impact, he said:

"We believe Lit is very likely a virulence factor, negatively impacting host immune response to infection. As such, it could well turn out to be an important target for the development of critically needed antibiotics against which resistance is much less likely to evolve. And it is no exaggeration to say that antibiotic resistance poses a genuine, growing threat to our society.

"With a high-resolution crystal structure and a strong foundation for understanding how it functions in bacterial cells, we are in a similar position to where we were four years ago when we published similar work concerning a related lipoprotein processing enzyme, known as lipoprotein signal peptidase II (or LspA). LspA is currently under intense scrutiny as an antibiotic target by several research groups - including ours in TBSI - and by a number of pharmaceutical companies."

Oncotarget published "A novel E2F1-regulated lncRNA, LAPAS1, is required for S phase progression and cell proliferation" which reported that long non-coding RNAs are major regulators of many cellular processes, including cell cycle progression and cell proliferation.

Inhibition of LAPAS1 expression increases the percentage of S phase cells, and its silencing in synchronized cells delays their progression through S phase.

In agreement with its suggested role in cell cycle progression, prolonged inhibition of LAPAS1 attenuates proliferation of human cancer cells.

Importantly, knockdown of SPNS2 rescues the effect of LAPAS1 silencing on cell cycle and cell proliferation.

Summarily, they identify LAPAS1 as a novel E2F-regulated lncRNA that has a potential role in human cancer and regulates cell-cycle progression and cell proliferation, at least in part, via regulation of SPNS2.

They identify LAPAS1 as a novel E2F-regulated lncRNA that has a potential role in human cancer and regulates cell-cycle progression and cell proliferation

Dr. Doron Ginsberg from The Bar-Ilan University said, "The human genome expresses many thousands of long non-coding RNAs (lncRNAs), which are transcripts longer than 200 bases that lack a significant open reading frame."

Increasing evidence indicates that lncRNAs are key regulators of important biological processes including cell cycle progression, cell proliferation and apoptosis.

Specifically, some lncRNAs function in regulation of cell cycle progression via modulation of critical cell cycle players, such as the cyclins, CDKs, CDK inhibitors, pRB, and p53.

Transcription factors that regulate mRNA transcription were shown to also regulate lncRNAs expression.

Inhibition of LAPAS1 expression delays progression of cells through S phase and inhibits proliferation of human cancer cells.

Thus, the authors identify LAPAS1 as a new E2F-regulated lncRNA that has a potential role in human cancer and regulates cell proliferation and cell-cycle progression, at least in part, via regulation of SPNS2.

The Ginsberg Research Team concluded in their Oncotarget Research Output, "this study reports the identification of a novel lncRNA that affects cell cycle progression and cell proliferation and may affect cancer progression. Its initial characterization shows that it is transcriptionally regulated by E2F and it exerts its activity, at least in part, by regulating SPNS2."

Imagine sitting out in the sun, reading a digital screen as thin as paper, but seeing the same image quality as if you were indoors. Thanks to research from Chalmers University of Technology, Sweden, it could soon be a reality. A new type of reflective screen - sometimes described as 'electronic paper' - offers optimal colour display, while using ambient light to keep energy consumption to a minimum.

Traditional digital screens use a backlight to illuminate the text or images displayed upon them. This is fine indoors, but we've all experienced the difficulties of viewing such screens in bright sunshine. Reflective screens, however, attempt to use the ambient light, mimicking the way our eyes respond to natural paper.

"For reflective screens to compete with the energy-intensive digital screens that we use today, images and colours must be reproduced with the same high quality. That will be the real breakthrough. Our research now shows how the technology can be optimised, making it attractive for commercial use," says Marika Gugole, Doctoral Student at the Department of Chemistry and Chemical Engineering at Chalmers University of Technology.

The researchers had already previously succeeded in developing an ultra-thin, flexible material that reproduces all the colours an LED screen can display, while requiring only a tenth of the energy that a standard tablet consumes.

But in the earlier design the colours on the reflective screen did not display with optimal quality. Now the new study, published in the journal Nano Letters takes the material one step further. Using a previously researched, porous and nanostructured material, containing tungsten trioxide, gold and platinum, they tried a new tactic - inverting the design in such a way as to allow the colours to appear much more accurately on the screen.

Inverting the design for top quality colour

The inversion of the design represents a great step forward. They placed the component which makes the material electrically conductive underneath the pixelated nanostructure that reproduces the colours - instead of above it, as was previously the case. This new design means you look directly at the pixelated surface, therefore seeing the colours much more clearly.

In addition to the minimal energy consumption, reflective screens have other advantages. For example, they are much less tiring for the eyes compared to looking at a regular screen.

To make these reflective screens, certain rare metals are required - such as the gold and platinum - but because the final product is so thin, the amounts needed are very small. The researchers have high hopes that eventually, it will be possible to significantly reduce the quantities needed for production.

"Our main goal when developing these reflective screens, or 'electronic paper' as it is sometimes termed, is to find sustainable, energy-saving solutions. And in this case, energy consumption is almost zero because we simply use the ambient light of the surroundings," explains research leader Andreas Dahlin, Professor at the Department of Chemistry and Chemical Engineering at Chalmers.

Flexible with a wide range of uses

Reflective screens are already available in some tablets today, but they only display the colours black and white well, which limits their use.

"A large industrial player with the right technical competence could, in principle, start developing a product with the new technology within a couple of months," says Andreas Dahlin, who envisions a number of further applications. In addition to smart phones and tablets, it could also be useful for outdoor advertising, offering energy and resource savings compared with both printed posters or moving digital screens.

More about the research

Research on the nano-thin electronic paper has been ongoing for several years at Chalmers, and the work has been rewarded with both international attention and major strategic research grants.

The technology in Chalmers researchers' reflective screens is based on the material's ability to regulate how light is absorbed and reflected. In the current study, tungsten trioxide is the core material, but in previous studies, researchers also used polymers. The material that covers the surface conducts electronic signals throughout the screen and can be patterned to create high-resolution images.

The scientific article Electrochromic Inorganic Nanostructures with High Chromaticity and Superior Brightness has been published in Nano Letters and is written by Marika Gugole, Oliver Olsson, Stefano Rossi, Magnus P. Jonsson and Andreas Dahlin. The researchers are active at Chalmers University of Technology and Linköping University.

Researchers have identified a specialized protein that appears to help prevent tumor cells from entering the bloodstream and spreading to other parts of the body.

"We have discovered that this protein, TRPM7, senses the pressure of fluid flowing in the circulation and stops the cells from spreading through the vascular system," said Kaustav Bera, a Johns Hopkins University PhD candidate in chemical and biomolecular engineering and a lead author of the study, which was done with colleagues at the University of Alberta and Universitat Pompeu Fabra.

"We found that metastatic tumor cells have markedly reduced levels of this sensor protein, and that is why they efficiently enter into the circulation rather than turning away from fluid flow," said Bera.

The findings, published in Science Advances, help shed light on a little-understood part of metastasis called intravasation, when cancer cells that have separated from a primary tumor enter the circulation in order to travel to other parts of the body and establish colonies.

The researchers further show that artificially increasing the expression of TRPM7 in tumor cells may help stop intravasation--and ultimately metastasis--in its tracks.

TRPM7 has long been known to regulate calcium in cells, but this new insight into its role in cell migration is exciting, according to the researchers. "The process is akin to what happens when you touch a hot kettle, feel it's hot, and remove your hand," said senior study author Konstantinos Konstantopoulos, a professor of chemical and biomolecular engineering and member of the Johns Hopkins Kimmel Cancer Center.

The protein senses the flow of the fluid in the circulatory system and instructs the cell to reverse direction, thereby inhibiting intravasation, he said.

Typically, the cells in the human body--for example, muscle cells, fat cells, and epithelial cells--stay contained in their respective regions. The major exception are blood cells, which patrol the body fighting pathogens. And then there are cancer cells, which have mutations that allow them to travel and spread.

It is at this point of spreading that cancer becomes much more dangerous. "Many people will be diagnosed with a primary tumor, but as long as this tumor is contained, a surgical procedure can save the person," said Christopher Yankaskas, a lead author and former member of Konstantopoulos's lab who is now a scientist at Thermo Fisher Scientific.

For their initial experiment, the researchers observed healthy fibroblast cells moving through microchannels arranged perpendicularly in a ladder-like configuration in which the fluid could be controlled. When these cells encountered channels where fluid was moving, they reversed their direction in response to the shear stress exerted from the flow. However, when the cells encountered channels where fluid wasn't moving, they proceeded into them.

The researchers then used a process known as RNA interference to block the cells from expressing TRPM7. What they observed was striking, they say. When this sensor protein was disabled, the healthy cells no longer reversed direction in response to the flow. "Imagine you then pick up the kettle with an oven mitt, which reduces your sensitivity to the heat," said Konstantopoulos.

In subsequent experiments the researchers found that normal cells had higher levels of TRPM7 than sarcoma cells (a type of cancerous tumor cells), and that artificially expressing the protein in the tumor cells increased their sensitivity to the fluid flow.

When the normal cells reverse their direction of migration, they avoid exposure to shear stress, but this is not the case for tumor cells, explained Konstantopoulos. "The tumor cells are less sensitive, and that's why they continue entering the circulatory system."

"The goal was to see if we could take these cancerous cells and make them behave like normal cells," said Bera. "And we managed to do that."

A separate analysis of human patient data showed that those with osteosarcoma, breast, gastric, and liver cancer who expressed high levels of TRPM7 were more likely to live longer than those with lower levels of the protein.

More research is needed, but the team hopes that the findings could eventually lead to new cancer therapies using CRISPR activation, an exciting emerging DNA editing tool.

"We'll need further developments before we can take this to the clinical setting, but we believe we provide, for the first time, a definitive picture of the role of TRPM7 in a crucial step of tumor metastasis," said Konstantopoulos.

Athletes may have more than twice the risk of irregular heart rhythm

Younger athletes are at greater risk of atrial fibrillation than older athletes, say researchers

Athletes appear to be almost two and half times more likely than non-athletes to experience irregular heart rhythms (atrial fibrillation), suggests new research published in the British Journal of Sports Medicine.

In addition, those athletes involved in mixed sports such as football, rugby or netball appear to have the highest risk when compared with athletes taking part in endurance sports such as Nordic skiing, orienteering or rowing.

Previous studies have shown that physical activity can improve cardiovascular health and is associated with reduced illness and deaths, but they have suggested there is a threshold beyond which exposure to increasing levels of exercise is linked to heart issues including atrial fibrillation - a condition that can raise the risk of stroke, heart failure and other heart-related problems.

UK researchers led by Canterbury Christ Church University in Canterbury set out to review existing studies on the subject and explore what impact the type of sport in which athletes took part had on their risk of atrial fibrillation to reach a more conclusive picture of overall prevalence among athletes.

They reviewed and analysed 13 suitable studies that were published between 1990 and December 2020 which had looked at athletes who took part in sports including cycling, running, swimming, Nordic skiing, orienteering, rowing, football, rugby, and netball.

The 13 studies included data on 70,478 participants, collectively, which included 63,662 controls and 6,816 athletes.

The authors found that the risk of atrial fibrillation was 2.46 times higher among athletes than non-athletes.

When the authors split the studies into those that involved participants with and without cardiovascular disease risk factors (such as type 2 diabetes and high blood pressure), they found there was no significant difference in the relative risk of atrial fibrillation in athletes and non-athletes with these risk factors.

However, in athletes and non-athletes without cardiovascular disease risk factors athletes had a significantly higher relative risk (3.7 times higher) of atrial fibrillation than non-athletes.

In addition, younger athletes (aged under 55) had a much higher risk (3.6 times) of atrial fibrillation than older athletes (aged 55 and older) who were 76% more likely to have the condition than non-athletes.

Analysis also showed that athletes taking part in mixed sports rather than endurance sports had a higher risk of atrial fibrillation.

Their study had some limitations such as the fact that it analysed research with different approaches such as case control and cohort design, and there was limited data on female athletes, making it difficult to look at the relative risk of atrial fibrillation by gender.

Nevertheless, the researchers conclude: "Athletes have a significantly greater likelihood of developing atrial fibrillation compared with non-athlete controls.

"Younger aged athletes have a greater relative risk of atrial fibrillation compared with older athletes; however, exercise dose parameters, including training and competition history, as well as potential gender differences for the risk of atrial fibrillation requires future research."

BOSTON - By implementing a long-term, prospective approach to the development of celiac disease, a collaborative group of researchers has identified substantial microbial changes in the intestines of at-risk infants before disease onset. Using advanced genomic sequencing techniques, MassGeneral Hospital for Children (MGHfC) researchers, along with colleagues from institutions in Italy and the University of Maryland, College Park, uncovered distinct preclinical alterations in several species, pathways and metabolites in children who developed celiac disease compared to at-risk children who did not develop celiac disease.

As part of the MGHfC Celiac Disease, Genomic, Microbiome and Metabolomic (CDGEMM) Study, researchers identified changes in the gut microbiomes (collection of microorganisms) and metabolomes (molecular components of cells and tissues) of infants that occurred months before celiac disease onset. Changes include an "increased abundance of pro-inflammatory species and decreased abundances of protective and anti-inflammatory species at various time points preceding the onset of the disease," according to the group's article published in the Proceedings of the National Academy of Sciences.

"In this proof-of-concept study, we compared the gut microbiome of 10 infants who went on to develop celiac disease to the gut microbiome of 10 infants who did not develop the autoimmune condition," says Maureen Leonard, MD, lead author and clinical director of the Center for Celiac Research and Treatment at MGHfC. "We found significant changes in the intestinal microbes, pathways and metabolites as early as 18 months before disease onset. This was much earlier than we expected," adds Leonard.

In CDGEMM, researchers in Italy, Spain and the U.S. are studying 500 genetically at-risk infants from birth through age ten, allowing them to track changes in gut microbiota before celiac disease develops. CDGEMM researchers have been collecting extensive blood and fecal samples and voluminous environmental data on each participant since 2014. In this study, researchers used metagenomic analysis that enabled them to link microbial composition with function, highlighting changes in pathways associated with either increased inflammatory processes or reduced inflammation. "This study demonstrates the power of next-generation sequencing coupled with bioinformatics to detect these important changes," says co-author Rita Colwell, PhD, from the Institute of Advanced Computer Studies, University of Maryland, College Park.

"We needed a longitudinal, birth-cohort study of these at-risk infants to move microbiome research from associative observations to more causative studies," says senior author Alessio Fasano, MD, director of the Center for Celiac Research and Treatment at MGHfC. "This approach will help us to develop novel strategies for the diagnosis and treatment of a variety of conditions in which the microbiome could play a pathogenic role," adds Fasano.

He suggests that these findings, if confirmed by larger datasets, may represent specific therapeutic targets for disease interception and possible prevention of celiac disease onset through microbiome manipulation during the preclinical phase. "With these findings, we anticipate that we will be able to distinguish who will remain healthy and who will develop celiac disease months before the onset of the disease," adds Fasano.

Better treatments of HER2-positive breast cancer are closer at hand, thanks to new research by a team led by Université de Montréal professor Jean-François Côté at the cytoskeleton organization and cell-migration research unit of the UdeM-affiliated Montreal Clinical Research Institute.

Published in PNAS, the journal of the U.S. National Academy of Sciences, the new research by Marie-Anne Goyette, a doctoral student in Côté's laboratory, reveals a highly promising therapeutic target to counter the HER2-positive breast cancer.

In HER2-positive breast cancer, a gene called HER2 is expressed that promotes an aggressive form of the disease. Affecting 20 per cent of women suffering from breast cancer in Canada, the HER2-positive subtype is associated with a poor prognosis.

What threatens the life of the majority of cancer patients is the power of tumour cells to spread and thus metastasize to other organs, which can interfere with vital body functions. Increasingly, personalized medicine has generated a lot of hope for patients expressing the HER2 gene, but relapses are frequent in many.

Immunotherapy is an important avenue for treating these drug-resistant patients, but so far with little apparent benefit. As a result, researchers are trying to deepen their understanding of the tumours' immune environment and thereby better target the treatments and those most likely to respond to them.

It is with this in mind that Côté's team studied an important phenomenon in solid tumours called hypoxia. Hypoxia is manifested by a lack of oxygen caused by the rapid growth of the tumour, and leads to the production of metastases, a weakened immune system and resistance to treatment. In short, by making tumours more aggressive while reducing the body's ability to defend itself, hypoxia promotes cancer progression, which can be fatal to those affected.

In a preclinical model, the IRCM team identified a protein called AXL whose action is crucial for hypoxia to take place. By blocking the action of this protein in the tumour, using various novel techniques, the team observed a recovery of blood vessels and a revitalization of the tumour's immune environment. Blocking the action of the tumour also reduced its ability to metastasize in other organs.

"It's as if we had succeeded, on the one hand, in breaking down the protective walls of the tumour against the immune system, thus making it more vulnerable to immunological treatments, and, on the other hand, in preventing the tumour from moving elsewhere," said Goyette, the new study's first author.

The potential of this study is all the more important as it opens the way for further research on the subject from the perspective of various fields of biomedical research, the researchers believe. The sharing of expertise has once again proved its worth, they say.

"Cutting-edge personalized medicine in immunology has faced significant resistance from this type of cancer and we had the expertise in molecular research to help overcome these obstacles," said Côté. "We have not only shed light on a central mechanism of the functioning of some of the most aggressive tumours, but in doing so we have also unveiled a way to create an environment conducive to more effective treatments."