Culture

Hamilton, ON (March 31, 2021) - A global study led by Hamilton scientists has found a link between eating processed meat and a higher risk of cardiovascular disease. The same study did not find the same link with unprocessed red meat or poultry.

The information comes from the diets and health outcomes of 134,297 people from 21 countries spanning five continents, who were tracked by researchers for data on meat consumption and cardiovascular illnesses.

After following the participants for almost a decade, the researchers found consumption of 150 grams or more of processed meat a week was associated with a 46 per cent higher risk of cardiovascular disease and a 51 per cent higher risk of death than those who ate no processed meat.

However, the researchers also found moderate levels of consumption of non-processed meats had a neutral effect on health.

"Evidence of an association between meat intake and cardiovascular disease is inconsistent. We therefore wanted to better understand the associations between intakes of unprocessed red meat, poultry, and processed meat with major cardiovascular disease events and mortality," said Romaina Iqbal, first author of the study and an associate professor at the Aga Khan University in Karachi, Pakistan.

"The totality of the available data indicates that consuming a modest amount of unprocessed meat as part of a healthy dietary pattern is unlikely to be harmful," said Mahshid Dehghan, investigator for the Population Health Research Institute (PHRI) of McMaster University and Hamilton Health Sciences.

The Prospective Urban Rural Epidemiology (PURE) study was launched in 2003 and is the first multinational study that provides information on the association between unprocessed and processed meat intakes with health outcomes from low, middle and high-income countries.

"The PURE study examines substantially more diverse populations and broad patterns of diet, enabling us to provide new evidence that distinguishes between the effects of processed and unprocessed meats," said senior author Salim Yusuf, executive director of the PHRI.

Participants' dietary habits were recorded using food frequency questionnaires, while data was also collected on their mortality and major cardiovascular disease events. This allowed researchers to determine the associations between meat consumption patterns and cardiovascular disease events and mortality.

The authors believe that additional research may improve current understanding of the relationship between meat consumption and health outcomes. For example, it is unclear what study participants with lower meat intakes were eating instead of meat, and if the quality of those foods differed between countries.

Non-meat food substitutes may have implications in further interpreting the associations between meat consumption and health outcomes. Nonetheless, the study's authors believe their findings "indicate that limiting the intake of processed meat should be encouraged."

GENEVA, LAUSANNE, 31 March 2021: Cocaine is a highly addictive substance that, in the long term, can have adverse effects on health and wellbeing. There are around 18 million cocaine users globally, according to a UN report. Understanding how cocaine modifies brain networks could reveal potential targets for therapies to treat addiction and other neuropsychological disorders.

A new study published today in the journal Frontiers in Synaptic Neuroscience by a team of researchers from the University of Lausanne and the Wyss Center for Bio and Neuroengineering reveals that during cocaine withdrawal, neurons in a brain area associated with depression connect to neurons embedded in an anti-reward system.

When we receive a reward, neurons fire in the brain's ventral tegmental area (VTA) - a region of the brain that produces dopamine. Dopamine is a chemical messenger that creates feelings of joy or pleasure. It spreads throughout the brain, motivating us to repeat our actions and achieve the feeling of pleasure again, a central facet of addictive behavior.
When we miss out on a reward, or stop taking an addictive drug, the lateral habenula - a brain area linked to depression - becomes hyperactive and sends signals to the VTA that results in depressive symptoms.

What researchers did not know, until now, is exactly where the neurons from the lateral habenula extend into the VTA and what they connect to during withdrawal from cocaine. Through a series of experiments, the team discovered that, in mice, the neurons from the lateral habenula synapse mostly to neurons in the VTA that do not produce dopamine, creating a connection to an anti-reward system that may be key in driving adverse behavior.

Manuel Mameli, PhD, Associate Professor in the Department of Fundamental Neuroscience, University of Lausanne said: "We wanted to understand why individuals experience depression when they stop taking a substance like cocaine. We knew that cocaine withdrawal induces changes to brain circuits linked to depression and reward, but our results have now taken us a step further and show that there is a reorganization of brain circuits that drive negative behavior."

The team combined their expertise in sample preparation and advanced microscopy to capture 3D images of entire intact mouse brains. They used viral 'tags' to make the neurons fluoresce, then created completely transparent samples by removing lipids, before imaging with the Wyss Center's custom-built lightsheet microscope. With data analytics and visualization tools, they identified the 3D morphology of specific neurons to understand their anatomical distribution inside the brain.

Stephane Pages, PhD, Scientific Coordinator at the Wyss Center and Senior Research Associate at the University of Geneva said: "The beauty of lightsheet imaging is being able to see which neurons connect to each other in the brain. Our microscope and data analytics capabilities pinpointed the specific neuronal connections between the two major brain areas implicated in drug withdrawal."

The results of the study also show that neurons in the anti-reward circuits not only project to the VTA but also from there into other parts of the brain resulting in a cascade of 'anti-reward' information into areas responsible for decision making and motivation, amongst others. The next step is to dissect the functionality of these non-dopamine, anti-reward, circuits to better understand how they influence behavior.

DALLAS, March 31, 2021 -- Following a routine of regular physical activity combined with a diet including fruits, vegetables and other healthy foods may be key to middle-aged adults achieving optimal cardiometabolic health later in life, according to new research using data from the Framingham Heart Study published today in the Journal of the American Heart Association, an open access journal of the American Heart Association.

Cardiometabolic health risk factors include the metabolic syndrome, a cluster of disorders such as excess fat around the waist, insulin resistance and high blood pressure. Presence of the metabolic syndrome may increase the risk of developing heart disease, stroke and Type 2 diabetes.

Researchers noted it has been unclear whether adherence to both the U.S. Department of Health and Human Services' 2018 Physical Activity Guidelines for Americans and their 2015-2020 Dietary Guidelines for Americans - as opposed to only one of the two - in midlife confers the most favorable cardiometabolic health outcomes later in life. The physical activity guidelines recommend that adults achieve at least 150 minutes of moderate or 75 minutes of vigorous physical activity per week, such as walking or swimming. The dietary guidelines, which were updated in January 2021, offer suggestions for healthy eating patterns, nutritional targets and dietary limits.

In an analysis of data from participants of the Framingham Heart Study, which began more than 70 years ago in Framingham, Massachusetts, investigators examined data from 2,379 adults ages 18 and older and their adherence to the two guidelines. They observed that meeting a combination of the two recommendations during midlife was associated with lower odds of metabolic syndrome and developing serious health conditions as participants aged in their senior years in 2016-2019 examinations.

"Health care professionals could use these findings to further promote and emphasize to their patients the benefits of a healthy diet and a regular exercise schedule to avoid the development of numerous chronic health conditions in the present and in later life," said corresponding author Vanessa Xanthakis, Ph.D., FAHA, assistant professor of medicine and biostatistics in the Section of Preventive Medicine and Epidemiology at Boston University School of Medicine in Boston. "The earlier people make these lifestyle changes, the more likely they will be to lower their risk of cardiovascular-associated diseases later in life."

Study participants were selected from the third generation of the Framingham Heart Study. Participants (average age 47, 54% women) were examined between 2008 and 2011. Researchers evaluated physical activity using a specialized device known as an omnidirectional accelerometer. The device, which tracks sedentary and physical activity, was worn on the participant's hip for eight days. Researchers also collected dietary information from food frequency questionnaires to measure the kinds and levels of food and nutrients consumed.

In this investigation, researchers observed that among all participants, 28% met recommendations of both the physical activity and dietary guidelines, while 47% achieved the recommendations in only one of the guidelines. Researchers also observed that:

participants who followed the physical activity recommendations alone had 51% lower odds of metabolic syndrome;

participants who adhered to the dietary guidelines alone had 33% lower odds; and

participants who followed both guidelines had 65% lower odds of developing metabolic syndrome.

"It is noteworthy that we observed a dose-response association of adherence to diet and physical activity guidelines with risk of cardiometabolic disease later in life," Xanthakis said. "Participants who met the physical activity guidelines had progressively lower risk of cardiometabolic disease as they increased adherence to the dietary guidelines."

All study participants were white adults, therefore, the findings cannot be generalized to people in other racial or ethnic groups. Additional studies with a multiethnic participant sample are needed, researchers said.

More research is needed on the environmental impact of sunscreen on the world's coral reefs, scientists at the University of York say.

The concerns over the number of cases of cancer as a result of overexposure to UV solar radiation, has led to extensive production and use of skin protection products. The chemical compounds used in these products, however, can enter the environment at the points of manufacture as well as through use by the consumer.

It is already understood that UV-filter compounds have toxic effects on marine organisms, but research in this area is limited and does not take into account certain variables, such as differences in environmental conditions.

Dr Brett Sallach, from the University of York's Department of Environment and Geography, said: "Given the declining status of coral reef ecosystems and the many stressors they already face, it is important to identify the potential occurrence and toxicological risks associated with UV-filter exposure to reef ecosystems.

"Our research aimed to identify what research was out there and what gaps we had in our knowledge. Importantly we needed to understand what areas could be considered priority for future attention in order to understand the impacts of these products, and hopefully prevent any further damage to the environment.

"Undoubtedly products that can help protect against the harmful effects of UV radiation on human health are hugely important, and therefore we need reliable and extensive evidence to suggest any changes or scaling back of these products."

Researchers consulted with experts and industry representatives within the field of marine UV-filter exposure to understand the limitations of current research and what areas needed urgent attention.

They found that the majority of research on UV-filter compounds focuses on freshwater organisms and ecosystems, and that environmental conditions can either increase or decrease the response to toxic elements, making the true risk of the compounds difficult to establish.

This research does not translate easily to the unique ecology of coral reefs, and therefore long-term environmental monitoring would be needed in tropical and subtropical climates to understand the toxic effects here.

Yasmine Watkins, who led the work as part of her Masters degree in the Department of Environment and Geography, said: "We make four recommendations for priority research areas going forward, based on our consultation with experts. We need more work in the area of understanding UV-filter toxicity under different climate conditions, and long-term study into exposure and recovery of coral reefs.

"We also need to know realistic exposure to these compounds and how long they exist in the marine environment, to determine what the 'safe' limits are."

Researchers aim to highlight these priority areas to better inform regulators and policy makers to improve conservation and management of coral reefs, whilst ensuring that human health can continue to be protected by UV-filter products.

A*STAR's Institute of Bioengineering and Nanotechnology (IBN) has teamed up with Singapore Institute of Advanced Medicine Holdings Pte Ltd (SIAMH) to establish the first of its kind in-vitro patient-derived 3D organoid models of Nasopharyngeal Cancer (NPC).

The study was published in Frontiers in Oncology on 23 February 2021. It is the first direct experimental evidence to predict optimal Radiation Treatment (RT) boost dose required to cause sufficient damage to recurrent hypoxic (low oxygen level) NPC tumour cells, which can be further used to develop dose-painting algorithms in clinical practice.

Two patient-derived xenograft (PDX) lines were used to further establish in-vitro 3D models of hypoxic radioresistant NPC for the first time. This collaboration helps to fine-tune radiation treatment, lower the chances of recurrence of NPC and reduce the mortality rate.

Nasopharyngeal carcinoma is endemic in east and southeast Asia, where 95% of the cases are invariably associated with Epstein-Barr virus (EBV) infection. More than 50% of the patients present with locally advanced and distant metastasis during initial diagnosis, and the 5-year survival rate reduces to between 50% to 70%. The disease is most prevalent in Brunei, Maldives, Indonesia, and Singapore.

The current treatment for NPC includes Radiation Treatment. There are recurrent cases that occur due to insufficient radiation. This poses a clinical challenge to the oncologists. Usually, radiotherapy is used as a re-treatment on inoperable advanced recurrent cases. This results in patients having complications during treatment and the 5-year survival rate will be reduced further. With no relevant in-vitro models to study NPC except the C666-1 cell-line which was established in late 1990's, the lack of disease-specific in-vitro models of NPC has further hindered the development of personalised therapeutic options.

IBN and SIAMH collaborated with the Singapore General Hospital and The Hong Kong University of Science and Technology to create the new in-vitro hypoxic 3D organoid models. These mimicked the hypoxic radioresistant sub-volumes of recurrent NPC, and were found to closely resemble NPC patient tumours.

By using novel patient-derived 3D models, IBN and SIAMH were able to determine experimentally on the radiobiological parameters which provide a better guide in radiation dosing, such that hypoxic radioresistant NPC cells could be eliminated, thus reducing the chances of tumour recurrences.

The study has demonstrated that radiation dose escalation by about 1.4 folds to the hypoxic radioresistant areas in the tumour would further improve the outcome of the treatment. Delivering high dose radiation - in a smaller number of fractions (hypofractionated radiotherapy) may be the way to treat hypoxic radioresistant NPCs. This could reduce long-term side effects, mortality rates due to recurrence, and improve patients' quality of life.

Dr Lucky Sasidharan, Postdoctoral Fellow at A*STAR's IBN and first author of the Frontiers in Oncology paper said, "These insights may help to develop personalised radiotherapy regimens and dose painting algorithms which could save time and lives through the prevention of re-irradiation or re-treatment."

Dr Djeng Shih Kien, Chairman and CEO of SIAMH said, "We are indeed very happy to work with IBN and contribute towards the findings of escalating dose and fractionation of radiotherapy in the treatment of hypoxic radioresistant Nasopharyngeal carcinoma.

The use of in-vitro 3D organoid models of patient-derived xenografts for the first time opens up unlimited opportunities for further research with proton beams when it is available towards the end of 2021.

SIAMH's Proton Therapy Centre is a member of the FlashForwardTM Consortium and it will be extremely exciting to study the effects of Flash Therapy on hypoxic radioresistant 3D models of NPC."

IBN is planning to work with experts at the Proton Therapy Centre located in Biopolis on this study for evaluating the effects and benefit of utilising Proton therapy and Ultra-High Dose Rate (FLASH) Radiotherapy for the treatment of NPC. These new platforms would also add the advantage of delivering very high radiation doses in sub-seconds with high precision targeting on just the areas of the tumours -and sparing the surrounding normal tissues. IBN and SIAMH have been collaborating since 2019 to explore how to better tackle NPC.

Researchers from Loyola Marymount University, San Diego State University, Indian Institute of Management, and Iowa State University published a new paper in the Journal of Marketing that examines how effective marketplace participation by subsistence consumers requires knowledge and skills that relate to what, how, and why to participate.

The study, forthcoming in the Journal of Marketing, is titled "Marketplace Literacy as a Pathway to a Better World: Evidence from Field Experiments in Low-Access Subsistence Marketplaces" and is authored by Madhu Viswanathan, Nita Umashankar, Arun Sreekumar, and Ashley Goreczny.

Success for marketers looking to emerging markets for growth is inextricably linked to the wellbeing of the hundreds of millions of subsistence consumers and microentrepreneurs who face poor infrastructure, material resource constraints, and low literacy. Such markets are some of the fastest growing in the world, with nearly $5 trillion of consumption spending annually. As a result, many multinational companies (e.g., Proctor & Gamble, Nokia, Unilever) market products to subsistence consumers.

Unique to subsistence marketplaces is that micro-entrepreneurship serves as a primary source of livelihood, and consumers' purchasing power depends on their microenterprise success. A primary disconnect between marketers' engagement in such markets and subsistence consumers' demand for their products, however, is the latter's inability to participate in marketplaces effectively and beneficially.

Beneficial marketplace participation involves consumers making optimal decisions and generating income by creating value for others through micro-entrepreneurship. With low marketplace participation and suboptimal decision making, firms may sell substandard products rather than high-quality and valuable products. Moreover, firms might not partner with local entrepreneurs, which is an important strategy for market entry in emerging markets.

Viswanathan explains that "Our research demonstrates that subsistence consumers' effective and beneficial marketplace participation requires not only material resources, such as access to capital, but also marketplace literacy--the knowledge and skills that enable marketplace participation both as a consumer and as an entrepreneur." Umashankar adds that "Marketplace literacy causes an increase in psychological wellbeing and consumer outcomes related to wellbeing like consumer confidence and decision-making ability, especially for subsistence consumers with lower marketplace access. It also causes an increase in entrepreneurial outcomes related to wellbeing, such as starting a microenterprise, for those with higher marketplace access."

The research provides insights for public policy makers, development efforts, and companies' corporate social responsibility initiatives. First, subsistence consumers play a significant role in mainstream marketing research since they represent a sizable proportion of consumers globally and function in extreme conditions that challenge the theories developed for resource-rich consumers and markets. Second, marketplace literacy offers a pathway to a better world for subsistence consumers. This pathway is fundamentally about literacy in a marketing domain, which encompasses buyers, sellers, and their interactions. Third, marketplace access is an important contextual factor that should be considered when exploring marketing phenomena across income levels. Fourth, marketplace literacy is a critical form of literacy, in addition to consumer and financial literacy, that should be cultivated. Fifth, marketplace literacy interventions should be implemented to help subsistence consumers overcome their lack of marketplace access and allow them to engage in entrepreneurship.

Even brief programs (4 to 12 hours) with rudimentary methods can aid the development of marketplace literacy and generate substantive outcomes. Such programs can be customized for different audiences (e.g., women vs. men) and occupations (farmers vs. artists) and can have their causal impact assessed. Lessons can be reinforced through short clips on web-based smartphone applications (e.g., WhatsApp, which has widespread adoption, even in rural areas of developing economies) or through text messages.

Given that multinational firms engage in corporate social responsibility initiatives to build stakeholder engagement, policymakers should hold marketers accountable for playing a central role in engendering marketplace literacy. This can be achieved through consumer and entrepreneur protection agencies, subsidies, and metrics that reward firms adhering to such standards. Sreekumar says that "We recommend that the United Nations include marketplace literacy explicitly in its sustainable development goals to build consumer and entrepreneurial knowledge and skills."

Chestnut Hill, Mass. (3/31/21) -- Spinach, a cost-efficient and environmentally friendly scaffold, provided an edible platform upon which a team of researchers led by a Boston College engineer has grown meat cells, an advance that may accelerate the development of cultured meat, according to a new report in the advance online edition of the journal Food BioScience.

Stripped of all but its veiny skeleton, the circulatory network of a spinach leaf successfully served as an edible substrate upon which the researchers grew bovine animal protein, said Boston College Professor of Engineering Glenn Gaudette, the lead author of the new study. The results may help increase the production of cellular agriculture products to meet rising demand and reduce environmental costs.

"Cellular agriculture has the potential to produce meat that replicates the structure of traditionally grown meat while minimizing the land and water requirements," said Gaudette, the inaugural chair of BC's new Engineering Department. "We demonstrate that decellularizing spinach leaves can be used as an edible scaffold to grow bovine muscle cells as they develop into meat."

Earlier advances by Gaudette in this area garnered worldwide attention. In 2017, Gaudette and a multi-university team showed that human heart tissue could be cultivated on a spinach leaf scaffold, which was chosen because it offered a natural circulatory system that is nearly impossible to replicate with available scientific tools and techniques.

"In our previous work, we demonstrated that spinach leaves could be used to create heart muscle patches," said Gaudette. "Instead of using spinach to regrow replacement human parts, this latest project demonstrates that we can use spinach to grow meat."

Gaudette said the team, which included Worcester Polytechnic Institute graduate students Jordan Jones and Alex Rebello, removed the plant cells from the spinach leaf and used the remaining vascular framework to grow isolated cow precursor meat cells. The cells remained viable for up to 14 days and differentiated into muscle mass.

"We need environmentally and ethically friendly ways to grow meat in order to feed the growing population," said Gaudette, whose research is supported by New Harvest. "We set out to see if we can use an edible scaffold to accomplish this. Muscle cells are anchorage dependent, meaning they need to grab on to something in order to grow. In the lab, we can use plastic tissue culture plates, but plastic is not edible."

The researchers point out that the successful results will lead to further characterization of the materials and scientific processes to better understand how to meet consumer demand and gauge how large-scale production could be accomplished in accordance with health and safety guidelines.

"We need to scale this up by growing more cells on the leaves to create a thicker steak," said Guadette. "In addition, we are looking at other vegetables and other animal and fish cells."

LA JOLLA, CA--The faster-spreading B.1.1.7 variant of SARS-CoV-2 first detected in the United Kingdom, the coronavirus that causes COVID-19, is quickly on its way to becoming the dominant variant of the virus in the United States, according to a study from scientists at Scripps Research and the COVID-19 test maker Helix.

The findings, which appear today in Cell, suggest that future COVID-19 case numbers and mortality rates in the United States will be higher than would have been otherwise. The analysis suggests that the variant, which has been detectable in an increasing proportion of SARS-CoV-2 samples, is 40-50 percent more transmissible than SARS-CoV-2 lineages that were previously dominant. Other studies have found evidence that the B.1.1.7 variant may be about 50 percent more likely to cause fatal COVID-19.

"B.1.1.7 rapidly became the dominant SARS-CoV-2 variant in the U.K. and other countries after its emergence late last year, and the U.S. is now on a similar trajectory," says study co-senior author Kristian Andersen, PhD, a professor in the Department of Immunology and Microbiology at Scripps Research and director of Infectious Disease Genomics at the Scripps Research Translational Research Institute. "We need immediate and decisive action to minimize COVID-19 morbidity and mortality."

In addition to Andersen, the other senior author was William Lee, PhD, vice president of science at Helix, which provides PCR-based COVID-19 testing to organizations across the United States. The study was also authored by Nicole Washington, PhD, associate director of research at Helix, and Karthik Gangavarapu of the Andersen Lab.

"B.1.1.7 has a doubling rate of a little over a week and an increased transmission rate of 40-50 percent, which means it could have a meaningful impact on public health," says Lee. "It is critical that we continue to monitor the spread of this and other emerging variants, but our current level of surveillance is inadequate and lags behind that of other countries. We need a more comprehensive national SARS-CoV-2 genomics surveillance program to address this."

The B.1.1.7 variant emerged in southern England last year and has since become the dominant variant in the U.K. In December, Andersen's team at Scripps Research with colleagues at University of California, San Diego confirmed the first evidence of the variant in California.

A pattern of dominance

The B.1.1.7 variant contains several mutations, including several in the gene that encodes the viral spike protein. These mutations increase the spike's ability to bind to the ACE2 receptor on human cells. Although there is no evidence yet that the B.1.1.7 variant can evade COVID-19 vaccines, public health officials fear its relatively high rate of spread will significantly worsen the pandemic before vaccines can end it.

Standard swab tests for the coronavirus check for distinctive genetic sequences at three sites on the viral genome; the B.1.1.7 variant, due to its mutations, shows up as positive for two of those sites, but negative for the third site, which is within the virus's spike gene.

The new analysis of roughly 500,000 Helix test results since July 2020 revealed that this two-of-three pattern, known as S-gene target failure, or SGTF, became consistently evident at a low frequency (0.2 percent) in mid-October. By the third week of February, it had risen to a frequency of 10.6 percent and was detected in patients from 25 different U.S. states and territories.

The SGTF pattern can occur with other SARS-CoV-2 variants that have spike gene mutations, but the researchers found by sequencing every SGTF sample they had from December through February, 662 of the 986 samples (67 percent) contained the B.1.1.7 variant. This suggests that the SGTF pattern on the swab tests can provide a quick albeit rough indication of B.1.1.7 prevalence.

Variant entered the country many times

The analysis also indicated that B.1.1.7 since December has accounted for a rapidly rising proportion of SGTF results--for example, reaching about 95 percent in California by mid-January. In addition to the 659 B.1.1.7 cases they detected via the SGTF method the researchers found three other cases of the B.1.1.7 variant among samples gathered as part of unbiased SARS-CoV-2 genomic surveillance efforts in California.

The 662 instances of B.1.1.7 sequenced in the study were from samples gathered in 10 U.S. states, although the researchers note that other testing labs covering a total of 33 U.S. states and territories have by now reported to the CDC at least one B.1.1.7 case.

The researchers' family tree-type analysis of the detected B.1.1.7 sequences show the variant has been introduced to the U.S. multiple times since at least late November 2020, especially in California and Florida, and in periods coinciding with increased travel, including Thanksgiving week.

The scientists also found that the variant, on the whole, appears to be spreading 40-50 percent faster than the variants of SARS-CoV-2 that previously dominated. They estimated that by the first week of February 2021, B.1.1.7 made up about 4.3 percent of COVID-19 cases in the U.S., including 4.2 percent of cases in California and about 11.5 percent of cases in Florida.

Nagoya University researchers have identified a gene that plays a crucial role in regenerating neurons of African clawed frog tadpoles, which has an unusually high capacity for nerve regeneration. Their study, recently published in the journal iScience, showed that introducing the gene into mice with spinal cord injury (SCI) led to a partial recovery of their lost motor functions. These findings could contribute to the development of a new therapy for SCI, which often causes a person to experience permanent and severe physical and neurological disabilities.

Repairing spinal cord injuries in humans and other mammals is difficult, partly because of their limited ability to repair and regenerate neural tissues in the spinal cord. In contrast, there are animals with a high capacity for nerve regeneration, such as the African clawed frog. "As a tadpole, it is fully capable of functional recovery after a spinal cord injury," said Drs. Dasfne Lee-Liu and Juan Larrain from the P. Universidad Catolica de Chile in their study, "Genome-wide expression profile of the response to spinal cord injury in Xenopus laevis reveals extensive differences between regenerative and non-regenerative stages," published in 2014.

In this context, the Nagoya University research team conducted a collaborative study with Drs. Lee-Liu and Larrain to identify transcription factors that regulate nerve regeneration in the African clawed frog tadpole, with the aim of inducing regenerative effects in mammals. The team comprehensively analyzed the gene expression profiles of tadpoles in response to SCI, and found that a gene called Neurod4 was expressed predominantly during nerve regeneration. The team thus hypothesized that this gene is a key factor in the regeneration of neural tissues after an injury.

In this study, the team also focused on the fact that in mammals, neural stem cells (known as self-renewing cells) derived from the ependymal cells lining the central canal of the spinal cord are activated and proliferate in the early stage of SCI, although these types of neural stem cells eventually transform into astrocytes -- a type of cell that forms rigid glial scars.

"Taking these things together, we thought that introducing Neurod4 into activated neural stem cells may help regenerate neurons," said Associate Professor Atsushi Natsume of the Nagoya University Graduate School of Medicine, the corresponding author of the study.

To that end, the team conducted experiments in which the Neurod4 gene was introduced to activated neural stem cells in mice just after SCI. The researchers observed that the neural stem cells were successfully converted into neurons and, interestingly, the mice occasionally moved their paralyzed hind legs. Dr. Natsume explained, "Neurod4 introduced into activated neural stem cells facilitates the production of relay neurons, which project to motor neurons of the hind legs. As a secondary effect, glial scar formation was suppressed after the subacute phase of spinal cord injury. This effect allows an environment that was conducive for axons to elongate beyond the injury site and form synapses, thereby improving the motor function of the hind legs."

"Our method is to introduce a neuro regenerative gene directly into neural stem cells that are already present in the spinal cord. This could lessen the problems of rejection and tumor formation, which often occur in conventional stem cell transplantation methods. We believe this study will contribute to the development of new therapeutic approaches to spinal cord injury," he added.

Researchers from University of Tübingen (Tübingen, Germany) and Ural Federal University (Ekaterinburg, Russia) have developed and experimentally tested new method to understand how the brain builds associations between previously unrelated words. The findings are published in Journal of Neurolinguistics.

The scientists conducted used electroencephalography to measure how the brain responds to the incongruent sentence endings. So, the brain responses to the last word in the phrase "I like my coffee with cream and sugar" have much smaller magnitude as compared to the phrase "I like my coffee with cream and socks". The brain reacts in a similar way to words in pairs such as cat-dog and cat-sky.

"We get a neural index of how people learn new associations between words, in fact - a language," said researcher of Department of Psychology at Ural Federal University and Institute of Medical Psychology and Behavioral Neurobiology at University of Tübingen Yuri Pavlov. "At the same time, this index is completely independent from behavioral responses. The brain itself informs us what it has learnt."

At first stage of the experiment the participants listened to five pairs of semantically unrelated words, each pair repeated twenty times. To give an example, the participants could hear such word pairs as carriage-text, death-fruit, seriousness-cow. Then, to the freshly learnt pairs, new similarly weird but new pairs were added. The experiment showed that the brain responses to the learnt word pairs rapidly attenuated and, after twenty repetitions, did not differ from the responses to familiar word pairs such as coffee-cream.

In the future, the scientists plan to apply the developed experimental paradigm to patients in disorders of consciousness.

"Perhaps those patients whose brains preserve the ability to learn new semantic associations have a chance to regain consciousness," said Yuri Pavlov. "Indeed, such an ability depends on a multiverse of cognitive functions such as long-term and working memory, speech perceptionThis means that we can suspect that the underlying anatomical and functional connections within the brain are not entirely destroyed. It is even possible that the patient is conscious, but cannot inform us about this by speech or gestures."

The protein Asc-1 regulates whether fat-burning beige or fat-storing white adipocytes are formed, which can have an impact on the development of metabolic diseases. This is shown by a current study of the Helmholtz Zentrum München and the German Center for Diabetes Research (DZD). The results open up new approaches to prevent the development of metabolic diseases. The study has now been published in Nature Communications.

Not all fat is the same: there is white, brown and beige adipose tissue *. While white fat cells serve as energy stores, excess energy is burned in brown and beige fat tissue. Too much white fat is considered unhealthy. If the white adipose tissue increases significantly in adults with obesity, metabolic diseases such as diabetes or metabolic syndrome can develop. The situation is different in children: There, the initial formation of white adipose tissue is a prerequisite for a healthy metabolism. But how does adolescent adipose tissue differs from adult white adipose tissue? To answer this question, researchers have investigated the composition of white adipose tissue of young and adult mice using single cell RNA sequencing**.

Asc-1 promotes the formation of white adipocytes

The researchers found that adolescent adipose tissue differs greatly from adult white fat, especially in terms of the properties and composition of fat precursor cells. The researchers discovered a special subgroup of fat precursor cells in adolescent adipose tissue that contain the protein Asc-1, which is otherwise present in mature adipocytes. These precursor cells differentiate predominantly into white adipocytes, and the formation of "healthy" beige adipocytes is actively suppressed. In further cell biological investigations, the team around first author Lisa Suwandhi were able to show that the loss of Asc-1 function promotes the formation of beige adipocytes.

"These insights into the physiological processes of adipose tissue growth enable us to develop new strategies to prevent the harmful metabolic consequences of obesity," said last author Dr. Siegfried Ussar. The researchers are already pursuing this approach further. They are currently establishing strategies to modulate Asc-1 function in adipose tissue in the living organism and exploring ways to promote healthy adipose tissue expansion. The goal is to help obese patients maintain a healthy metabolism in the future and thus gain time to treat obesity with a holistic approach.

A thermos bottle has the task of preserving the temperature - but sometimes you want to achieve the opposite: Computer chips generate heat that must be dissipated as quickly as possible so that the chip is not destroyed. This requires special materials with particularly good heat conduction properties.

In collaboration with groups from China and the United States, a research team from TU Wien therefore set out to find the optimal heat conductor. They finally found what they were looking for in a very specific form of tantalum nitride - no other known metallic material has a higher thermal conductivity. In order to be able to identify this record-breaking material, they first had to analyse which processes play a role in heat conduction in such materials at the atomic level. The results have now been published in the scientific journal Physical Review Letters.

Electrons and lattice vibrations

"Basically, there are two mechanisms by which heat propagates in a material," explains Prof. Georg Madsen from the Institute of Materials Chemistry at TU Wien. "Firstly, through the electrons that travel through the material, taking energy with them. This is the main mechanism in good electrical conductors. And secondly through the phonons, which are collective lattice vibrations in the material." The atoms move, causing other atoms to wobble. At higher temperatures, heat conduction through propagation of these vibrations is usually the decisive effect.

But neither the electrons nor the lattice vibrations can propagate completely unhindered through the material. There are various processes that slow down this propagation of thermal energy. Electrons and lattice vibrations can interact with each other, they can scatter, they can be stopped by irregularities in the material.

In some cases, heat conduction can even be dramatically limited by the fact that different isotopes of an element are built into the material - i.e. similar atoms with different numbers of neutrons. In that case, the atoms do not have exactly the same mass, and this affects the collective vibrational behaviour of the atoms in the material.

"Some of these effects can be suppressed - but usually not all at the same time," says Georg Madsen. "It's like playing Whack-A-Mole: You solve one problem, and at the same time a new one arises somewhere else."

Tantalum nitride, the all-rounder

Despite our everyday experience of burning our hands on a hot metal plate, metals typically have a mediocre thermal conductivity. The metal with the highest known thermal conductivity is silver - with only a fraction of the conductivity of the record holding material diamond. But diamonds are expensive and very difficult to process.

With elaborate theoretical analyses and computer simulations, the team finally succeeded in identifying a suitable material: The hexagonal θ-phase of tantalum nitride. Tantalum is particularly favourable because there are hardly any different isotopes. Almost 99.99% of the naturally occurring tantalum is the isotope tantalum 181, other variants hardly occur.

"The combination with nitrogen and the special atomic scale geometry make the phase metallic, and it suppresses interactions of the heat carrying vibrations with other vibrations and with the conducting electrons. It is exactly those interactions that inhibit heat conduction in other materials," says Georg Madsen. "These interactions are not possible in this material because they would violate the law of energy conservation."

Therefore, this form of tantalum nitride combines several important advantages, making it a record-breaking material with a thermal conductivity several times higher than silver and comparable to diamond.

"For the chip industry, tantalum nitride is a highly promising material," Madsen is convinced. "Chips are getting smaller and more powerful, so conducting heat is becoming a bigger and bigger problem. No other material solves this problem better than the θ-phase tantalum nitride."

NEW YORK, NY (March 30, 2021)--Early in the pandemic, neurologists expressed concern that COVID-19 patients with dementia may be at higher risk for complications and mortality.

But those fears have not been realized, according to a new study of patients who were hospitalized with COVID-19 during the first wave of the pandemic in New York City. The study, led by James Noble, MD, MS, associate professor of neurology at Columbia University Vagelos College of Physicians and Surgeons and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, and Amro Harb, a Vagelos medical student, was published this month in the Journal of Alzheimer's Disease. 

Though the study found a greater proportion of patients with dementia had died, "other factors, including age and comorbidities, were really the driving factors and not dementia itself," Noble says.

One unmistakable difference among patients, however, was the greater incidence of delirium in those with dementia. 

"Early in the pandemic, we received many calls from caregivers about the sudden development of confusion and delirium in our dementia patients, even in those with only mild COVID symptoms," Noble says. "Delirium and confusion are common in elderly patients with other types of infections, including pneumonia, influenza, and urinary tract infections, and we realized delirium might be an unrecognized symptom of COVID-19 in this population."

That observation was reflected in the data from the hospitalized patients, where delirium was found in more than 36% of patients with dementia versus less than 12% of patients without dementia.

The dementia patients with COVID-19 were also less likely to report subjective symptoms such as shortness of breath, muscle aches, chills, nausea, or headaches compared with patients without dementia.

"It's hard to say if all of these are true differences," Noble says. "We know that, in general, people with dementia may be less likely to report some of the symptoms that we have come to recognize as typical COVID-19 symptoms because of poor awareness or they just don't remember to report these things." 

Regardless of the reason behind the differences, Noble says the study suggests we may need to look beyond conventional symptoms associated with COVID-19 in this population and consider confusion and delirium as possible common signs of infection.

"The CDC has recognized new confusion is a 'warning sign' of COVID-19, and this study suggests this symptom was especially common in people with dementia hospitalized with COVID-19," Noble says. "This is important for caregivers and health care providers of homebound Alzheimer's patients who have not been vaccinated yet."

Not all species may travel the same path to existence, at least according to new findings from the University of Colorado Boulder and collaborators.

This new research, out now in Science, looked at a newly discovered, endangered songbird located only in South America--the Iberá Seedeater--and found that this bird followed a very rare evolutionary path to come into existence at a much faster pace than the grand majority of species.

By comparing this bird to a closely related neighbor (the Tawny-Bellied Seedeater) in the same group (the southern capuchino seedeaters), the researchers determined that genetic shuffling of existing variations, rather than new random mutations, brought this species into existence--and their own behaviors are keeping them apart.

This species is one of only two known examples across the globe to have traveled this path, challenging the typical assumptions of how new species form.

"One of the aspects of this paper that makes it so cool is that we were able to address this question of how the Iberá Seedeaters formed from multiple different perspectives," said Sheela Turbek, a graduate student in ecology and evolutionary biology (EBIO) at University of Colorado Boulder and the study's lead author.

"Not only did we collect on-the-ground data on who mated with one another and the identity of their offspring, but we also generated genomic data to examine how similar these two species are on a genetic level. We then zoomed out further to look at where the Iberá Seedeater fits in the context of the broader capuchino group."

"Many studies will address one of these aspects or questions but not combine all of these different pieces of information into a single study."

The southern capuchino seedeaters are a group of recently evolved songbirds found throughout South America that is branching rapidly, with many of its species in the early stages of evolution. This family is best known for the dramatic variation with the males in terms of songs and plumage color, while the females are largely indistinguishable even to the most familiar researchers.

The Iberá Seedeater, the most recent member of this family, was first discovered in the remote, swampy grasslands of Iberá National Park in northern Argentina by study co-authors Adrián S. Di Giacomo and Cecilia Kopuchian from Centro de Ecología Aplicada del Litoral, Argentina, in 2001, and then described in scientific literature in 2016.

In that national park, though, are six other closely related species of capuchinos, including the Tawny-Bellied Seedeater, that breed closely beside each other. These species, despite occupying the same environment and eating the same food, rarely interbreed.

And so, researchers wondered why--and how--the Iberá Seedeater even came to be.

They explored these questions in two ways: First, they looked at how this new species may have formed by examining the ways in which its DNA differs from the Tawny-Bellied Seedeater, and second, looking at what mechanisms might be preventing it from interbreeding with the other species that occur in the park.

To do that, Turbek went down to Argentina for the breeding season for three years, staying two and a half to three months at a time, searching for and monitoring nests, collecting blood samples from adults and nestlings, and then, in the final year, performed a behavioral experiment to see whether plumage or song played a roll in terms of species recognition.

"The field work involved in collecting the assortative mating and behavioral data is extraordinarily hard, which is why these kinds of datasets rarely exist. This study and publication are a testament to Sheela's skill and hard work in the field," said Scott Taylor, an assistant professor in EBIO at University of Colorado Boulder, an author on the paper and Turbek's advisor.

What they found is that the two birds are closely related genetically, only distinguishable by the genes involved in plumage coloration. As well, they found that the males responded most aggressively to songs and plumage variations aligning with their own species.

This all means that the species could very well reproduce and hybridize--they just choose not to, therefore reinforcing their own reproductive barriers.

On a broader level, though, when comparing the Iberá Seedeater to other capuchino species, the researchers found that the Iberá Seedeater shares genomic variants with other capuchinos in these regions, but the variants have been shuffled to form a unique combination, which, the researchers argue, could be an evolutionary shortcut that most likely underlies much of the diversity among the different subspecies of this family.

"This is a really beautiful story about a process that we have never seen in quite this way before," says co-author Irby Lovette, director of the Fuller Evolutionary Biology Program at the Cornell Lab of Ornithology.

"The classic and most common evolutionary model for new species is the accumulation of genetic mutations when those species are separated by a geographic barrier over perhaps millions of years. But here we found that genetic shuffling can happen quickly and without geographical isolation. It's almost like 'instant speciation.'"

Leonardo Campagna, a research associate at the Cornell Lab of Ornithology and the senior author on the paper, agrees:

"This is the clearest example in birds of how reshuffling of genetic variation can generate a brand-new species."

The only other organism where this type of evolution has been seen, according to Turbek, is a group of fish found in Africa called the Lake Victoria cichlids.

"It's interesting to see this mechanism operating in something as different as birds," Turbek commented.

While this study focused in part on the role of male behaviors, the researchers are very interested in taking it one step further, examining the role that female choice may also play in reproduction.

"There are many more questions that we have to address," Turbek said.

Scientists have discovered a new genetic disease, which causes some children's brains to develop abnormally, resulting in delayed intellectual development and often early onset cataracts.

The majority of patients with the condition, which is so new it doesn't have a name yet, were also microcephalic, a birth defect where a baby's head is smaller than expected when compared to babies of the same sex and age.

Researchers from the universities of Portsmouth and Southampton found that changes in a gene called coat protein complex 1 (COPB1) caused this rare genetic disease.

Now the variant has been identified, it will help clinicians come up with targeted interventions to help patients and their families, also opening the door to screening and prenatal diagnosis.

The research team, made up of frog geneticists, medical genomic research scientists and clinical geneticists, sequenced the DNA of affected patients and their family members, which identified COPB1 as the potential underlying cause of the disease. Using tadpoles to mimic the human gene variants, the tadpoles with the COPB1 gene changes had variably smaller brains than the control tadpoles and many of them had cataracts, just like the patients. This showed the link between the gene and disease very clearly.

The findings are published in the journal Genome Medicine.

Study co-author Professor Matt Guille, who leads a laboratory in the Epigenetics and Developmental Biology research group at the University of Portsmouth, said: "This is the first time that the tadpole has been used in such a direct way to help solve a clinical challenge.

"In our initial experiments to test the link between a genetic variation and a disease we found to our surprise that by altering the DNA of tadpoles, four times out of five we could re-create the disease-related changes seen in human patients. This will allow us to support our colleagues in providing more timely, accurate diagnosis that patients and their families so desperately need."

Co-author Diana Baralle, Professor of Genomic medicine and a clinical geneticist at the University of Southampton, said: "Next generation sequencing is transforming our ability to make new diagnoses and discover new causes for rare disorders. This story started with sisters I saw in clinic without a known underlying cause for their signs and symptoms. Looking closely at their genes, along with further functional molecular work and xenopus studies, we saw that this was a new previously undescribed syndrome. A diagnosis is so important to the family."

One in 17 people will suffer from a rare disease at some time in their lives. Most of these rare diseases have a genetic cause and often affect children, but proving which gene change causes a disease is a huge challenge.

Professor Guille said that previously, while studies connecting a gene and a disease were mainly performed in mice; several labs, including his own at the University of Portsmouth, have recently shown that experiments in tadpoles can also provide very strong evidence about the function of variant human genes. The process of re-creating some gene variants in tadpoles is straightforward and can be done in as little as three days.

Professor Guille added: "We now need to extend and improve our technology to make it applicable to the wider range of disease-related DNA changes provided to us by our clinical collaborators.

"If the clinical researchers find the information sufficiently useful, then we will continue to work together to scale up the pipeline of gene function analysis so it can be used to direct effective interventions for a significant number of patients."