Culture

Baltimore, MD--The buildup of scar tissue makes recovery from torn rotator cuffs, jumper's knee, and other tendon injuries a painful, challenging process, often leading to secondary tendon ruptures. New research led by Carnegie's Chen-Ming Fan and published in Nature Cell Biology reveals the existence of tendon stem cells that could potentially be harnessed to improve tendon healing and even to avoid surgery.

"Tendons are connective tissue that tether our muscles to our bones," Fan explained. "They improve our stability and facilitate the transfer of force that allows us to move. But they are also particularly susceptible to injury and damage."

Unfortunately, once tendons are injured, they rarely fully recover, which can result in limited mobility and require long-term pain management or even surgery. The culprit is fibrous scars, which disrupt the tissue structure of the tendon.

Working with Carnegie's Tyler Harvey and Sara Flamenco, Fan revealed all of the cell types present in the Patellar tendon, found below the kneecap, including previously undefined tendon stem cells.

"Because tendon injuries rarely heal completely, it was thought that tendon stem cells might not exist," said lead author Harvey. "Many searched for them to no avail, but our work defined them for the first time."

Stem cells are "blank" cells associated with nearly every type of tissue, which have not fully differentiated into a specific functionality. They can also self-renew, creating a pool from which newly differentiated cell types can form to support a specific tissue's function. For example, muscle stem cells can differentiate into muscle cells. But until now, stem cells for the tendon were unknown.

Surprisingly, the team's research showed that both fibrous scar tissue cells and tendon stem cells originate in the same space--the protective cells that surround a tendon. What's more, these tendon stem cells are part of a competitive system with precursors of fibrous scars, which explains why tendon healing is such a challenge.

The team demonstrated that both tendon stem cells and scar tissue precursor cells are stimulated into action by a protein called platelet-derived growth factor-A. When tendon stem cells are altered so that they don't respond to this growth factor, then only scar tissue and no new tendon cells form after an injury.

"Tendon stem cells exist, but they must outcompete the scar tissue precursors in order to prevent the formation of difficult, fibrous scars," Fan explained. "Finding a therapeutic way to block the scar-forming cells and enhance the tendon stem cells could be a game-changer when it comes to treating tendon injuries.

Insurance schemes with the potential to improve the resilience of global fisheries face a host of future challenges, researchers say.

The world's first "Fisheries Index Insurance" scheme, launched by an international consortium in July, is a sovereign-level instrument designed to protect Caribbean fishing communities from extreme weather events which may become more frequent and intense due to climate change.

The team of scientists from the University of Exeter and Centre for Fisheries, Environment and Aquaculture Science (Cefas) today publish a letter in Nature Climate Change highlighting the challenges of extending climate risk insurance from agriculture to fisheries.

The lead author, Nigel Sainsbury, from the University of Exeter, said: "Climate risk insurance can help people and businesses involved in fisheries bounce back faster from extreme weather events, but it is important that this doesn't lead to less sustainable fishing outcomes and that more marginalised groups, particularly unregistered fishers and women involved in fisheries, don't miss out on payments."

The new insurance system may enable fishers to make decisions to postpone fishing in extreme weather, rather than risk a dangerous trip.

It can also help them to replace and repair fishing boats, gear, tools and infrastructure destroyed or damaged by storms much more rapidly.
Sainsbury added: "Extreme weather poses a direct threat to the lives of fishers and daily production, so the design of climate risk insurance needs to reflect this.

"Policymakers cannot rely solely on climate risk insurance in their climate adaptation plans.

"It must be complemented by adaptations actions in coastal ecosystems, such as the protection of mangroves, establishing pre-storm preparation plans and investment in less vulnerable fishing boats and gear."

The Caribbean Ocean and Aquaculture Sustainability faciliTy (COAST) unlocks insurance pay-outs to a pre-determined list of people and organisations involved in the fishing industry if an extreme weather event occurs and causes a set of environmental indicators - wave height, rainfall, wind speed and storm surge - to exceed pre-set thresholds.

COAST has been launched in St Lucia and Grenada. It is funded by the US State Department and relies on the specialist capabilities of the Caribbean Catastrophe Risk Insurance Facility (CCRIF SPC) and The World Bank.

Children's average daily time spent watching television or using a computer or mobile device increased from 53 minutes at age 12 months to more than 150 minutes at 3 years, according to an analysis by researchers at the National Institutes of Health, the University at Albany and the New York University Langone Medical Center. By age 8, children were more likely to log the highest amount of screen time if they had been in home-based childcare or were born to first-time mothers. The study appears in JAMA Pediatrics.

"Our results indicate that screen habits begin early," said Edwina Yeung, Ph.D., the study's senior author and an investigator in the Epidemiology Branch of NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). "This finding suggests that interventions to reduce screen time could have a better chance of success if introduced early."

NICHD researchers and their colleagues analyzed data from the Upstate KIDS Study, originally undertaken to follow the development of children conceived after infertility treatments and born in New York State from 2008 to 2010. Mothers of nearly 4,000 children who took part in the study responded to questions on their kids' media habits when they were 12, 18, 24, 30, and 36 months of age. They also responded to similar questions when the children were 7 and 8 years old. The study compiled additional demographic information on the mothers and children from birth records and other surveys.

The American Academy of Pediatrics recommends avoiding digital media exposure for children under 18 months of age, introducing children 18 to 24 months of age to screen media slowly, and limiting screen time to an hour a day for children from 2 to 5 years of age. In the current study, researchers found that 87% of the children had screen time exceeding these recommendations. However, while screen time increased throughout toddlerhood, by age 7 and 8, screen time fell to under 1.5 hours per day. The researchers believe this decrease relates to time consumed by school-related activities.

The study authors classified the children into two groups based on how much their average daily screen time increased from age 1 to age 3. The first group, 73% of the total, had the lowest increase, from an average of nearly 51 minutes a day to nearly an hour and 47 minutes a day. The second group, 27% of the total, had the highest increase, from nearly 37 minutes of screen time a day to about 4 hours a day. Higher levels of parental education were associated with lower odds of inclusion in the second group. In addition, girls were slightly less likely to be in the second group, compared to boys, while children of first-time mothers were more likely to be in the high-increase group.

The researchers also classified the children into percentiles based on their total daily screen time. Children were more likely to be in the 10th, or highest, percentile if their parents had only a high school diploma or equivalent (more than twice as likely) or were children of first-time mothers (almost twice as likely). Similarly, compared to single-born children, twins were more likely to belong to the highest screen time group. Compared to children in center-based care, children in home-based care, whether provided by a parent, babysitter or relative, were more than twice as likely to have high screen time.

New research led by the University of East Anglia (UEA) suggests that male migration and poor working conditions for women combine with institutional failure or poverty to hamper women's ability to adapt to climate variability and change in Asia and Africa.

There is growing concern about sustainable and equitable adaptation in climate change hotspots - locations where climatic shifts, social structures, and livelihood sensitivity converge to exacerbate vulnerability.

Examining gender within these debates highlights how demographic, socio-economic and agro-ecological circumstances combine in complex ways to impact the experiences and outcomes of climate change in specific contexts.

Entrenched social structures create power relations that shape women's and men's experiences of vulnerability through their access to resources, divisions of work, and cultural norms around mobility and decision-making, all of which determine their ability to adapt.

Drawing on data from 25 case studies across hotspots in Asia (India, Nepal, Pakistan, Bangladesh, Tajikistan) and Africa (Kenya, Ghana, Namibia, Mali, Ethiopia, Senegal), the study shows how and in what ways women's agency, or ability to make meaningful choices and strategic decisions, contributes to adaptation responses.

The study, published today in the journal Nature Climate Change, involved researchers from the UK, Nepal, India, Pakistan and South Africa. They argue that environmental stress weakens women's agency even when household structures and social norms are supportive, or legal entitlements available. This leads to household strategies that place increasing responsibilities and burdens on women, especially those who are young, less educated, and belonging to lower classes, or marginal castes and ethnicities.

While male migration for work does contribute to enhanced incomes, the degree of such support is both uncertain and irregular. Confronted with issues of everyday survival, in the absence of supportive infrastructure and services, women often work harder, in poorer conditions, and for lower wages, across the hotspots studied, with negative wellbeing outcomes, seen particularly in the neglect of their health and nutrition.

Lead author Prof Nitya Rao, of UEA's School of International Development, said: "In a sense, women do have voice and agency, as they are actively engaging in both production and reproduction, yet this is not contributing to strengthening longer-term adaptive capacities, or indeed their wellbeing.

"Our analysis suggests that some common conditions such as male migration and women's poor working conditions combine with either institutional failure, or poverty, to constrain women's ability to make choices and decisions. However these barriers, if addressed in creative ways, could potentially strengthen adaptive capacities, and enable more effective adaptation."

The findings have implications for the effective implementation of multilateral agreements such as the United Nations Framework Convention on Climate Change, through its Gender Action Plan, and commitments to gender-responsive adaptation as outlined in the Paris Agreement, along with the Sendai Framework for Disaster Risk Reduction and the Sustainable Development Goals.

These agreements require insights into what builds the adaptive capacity of women and men in specific contexts in order to support sustainable, equitable, and effective adaptation.

The authors suggest that, firstly, effective social protection, such as the universal public distribution system for cereals in India, or pensions and social grants in Namibia, can contribute to relieving immediate pressures on survival, creating some room for manouvre.

Secondly, rather than creating competition among individuals and households, such universal benefits can support processes that strengthen collective action at the community level. This however cannot always be done on the 'cheap'; investments are needed to enable better and more sustainable management of resources. Women's Self Help Groups are often presented as solutions, yet they are confronted by the lack of resources, skills and capacity to help their members effectively meet the challenges they confront.

While not discussed in depth in this paper, the authors say competitive markets are not working to strengthen women's agency, rather they end up undervaluing and appropriating the labour of poor women, but equally men in the case of migration.

"There appears to be a clear case for regulating labour markets to ensure decent work, whether for women or migrant men, but this is proving difficult in a globalised context," said Prof Rao.

The study uses case studies from three distinct regions: 14 in semi-arid regions, six in mountains and glacier fed river basins and five in deltas. Predominant livelihoods are agriculture, livestock pastoralism, and fishing, supplemented by wage labour, petty trade or business, and income from remittances.

These areas face a range of environmental risks including droughts, floods, rainfall variability, land erosion and landslides, heatwaves, coastal erosion and cyclones.

Hamilton, ON (Nov. 25, 2019) - Research led by scientists from McMaster University has yielded a potent antimicrobial that works against the toughest infectious disease strains. The find could be the beginning of developing new therapeutics to combat drug-resistant infections.

The discovery is important as it is directly related to the development of Staphylococcus aureus diseases, known popularly as staph infections, which are the leading cause of the growing global danger of antimicrobial resistance, particularly the Methicillin-resistant (MRSA) strains which are becoming resistant to all current antibiotics.

"This antimicrobial has a very exciting mode of action, kind of like hitting many birds with one stone," said Eric Brown, senior author and a professor of biochemistry and biomedical sciences at McMaster. "This provides a promising starting point."

After screening thousands of small molecules, the research team discovered a potent new antimicrobial they are calling MAC-545496 that is active against MRSA. Unlike conventional antibiotics, this new antimicrobial neither kills the staph infection nor halts its growth on its own, so the potential for antimicrobial resistance may be considerably lessened.

MAC-545496 cripples MRSA's ability to cause infection by diminishing its tolerance to the hostile components of the immune system and blocking the bacterium's capacity to resist the action of several front-line antibiotics.

To be more specific, the antimicrobial disarms MRSA from an important protein called GraR which enables the staph infection to respond to external threats, and allows the immune system to clear the infection more effectively. It also inhibits the ability of the MRSA to resist treatment by antibiotics.

First author Omar El-Halfawy, a postdoctoral fellow of biochemistry and biomedical sciences at McMaster, added: "We screened about 45,000 different compounds and found this potent bioactive, it's the needle in the haystack. But, although it will be a long road between this discovery and clinical use, we feel we're expanding our arsenal for combatting drug-resistant staph infections."

PULLMAN, Wash. - Inhaled cannabis reduces self-reported headache severity by 47.3% and migraine severity by 49.6%, according to a recent study led by Carrie Cuttler, a Washington State University assistant professor of psychology.

The study, published online recently in the Journal of Pain, is the first to use big data from headache and migraine patients using cannabis in real time. Previous studies have asked patients to recall the effect of cannabis use in the past. There has been one clinical trial indicating that cannabis was better than ibuprofen in alleviating headache, but it used nabilone, a synthetic cannabinoid drug.

"We were motivated to do this study because a substantial number of people say they use cannabis for headache and migraine, but surprisingly few studies had addressed the topic," said Cuttler, the lead author on the paper.

In the WSU study, researchers analyzed archival data from the Strainprint app, which allows patients to track symptoms before and after using medical cannabis purchased from Canadian producers and distributors. The information was submitted by more than 1,300 patients who used the app over 12,200 times to track changes in headache from before to after cannabis use, and another 653 who used the app more than 7,400 times to track changes in migraine severity.

"We wanted to approach this in an ecologically valid way, which is to look at actual patients using whole plant cannabis to medicate in their own homes and environments," Cuttler said. "These are also very big data, so we can more appropriately and accurately generalize to the greater population of patients using cannabis to manage these conditions."

Cuttler and her colleagues saw no evidence that cannabis caused "overuse headache," a pitfall of more conventional treatments which can make patients' headaches worse over time. However, they did see patients using larger doses of cannabis over time, indicting they may be developing tolerance to the drug.

The study found a small gender difference with significantly more sessions involving headache reduction reported by men (90.0%) than by women (89.1%). The researchers also noted that cannabis concentrates, such as cannabis oil, produced a larger reduction in headache severity ratings than cannabis flower.

There was, however, no significant difference in pain reduction among cannabis strains that were higher or lower in levels of tetrahydrocannabinol (THC) and cannabidiol (CBD), two of the most commonly studied chemical constituents in cannabis, also known as cannabinoids. Since cannabis is made up of over 100 cannabinoids, this finding suggests that different cannabinoids or other constituents like terpenes may play the central role in headache and migraine relief.

More research is needed, and Cuttler acknowledges the limitations of the Strainprint study since it relies on a self-selected group of people who may already anticipate that cannabis will work to alleviate their symptoms, and it was not possible to employ a placebo control group.

"I suspect there are some slight overestimates of effectiveness," said Cuttler. "My hope is that this research will motivate researchers to take on the difficult work of conducting placebo-controlled trials. In the meantime, this at least gives medical cannabis patients and their doctors a little more information about what they might expect from using cannabis to manage these conditions."

New biodegradable rods promise to provide better treatment for periodontal disease. Researchers from the Institute of Pharmacy at Martin Luther University Halle-Wittenberg (MLU) have re-combined an already approved active ingredient and filed for a patent for their invention together with two Fraunhofer Institutes from Halle. The innovation would spare patients from having many side effects. Their findings were published in the International Journal of Pharmaceutics.

Periodontal disease is widespread and usually caused by bacteria, which leads to an inflammation of the gums - the periodontitis. More than 50 % of adults in Germany develop periodontal disease in the course of their lives, mostly in old age. According to projections, more than ten million Germans have a severe form of the disease. "The body's barrier function is badly disrupted by the large wounds, allowing more substances and bacteria to enter the body," explains Professor Karsten Mäder, head of the Institute of Pharmacy at MLU. The inflammation affects the entire body and is often the cause of other diseases such as heart attacks or pneumonia. Therefore, mechanical cleaning procedures are often followed by antibiotics. These are usually administered in pill form, which puts a strain on the entire body. Common side effects are diarrhoea, abdominal pain and nausea as well as skin reactions such as redness and itching. The possible development of resistance to common antibiotics is also a major factor in this form of treatment.

Ideally, the antibiotic would only act locally in the mouth rather than throughout the entire body. Mäder's research group has therefore combined a proven antibiotic (minocycline) with an equally proven pharmaceutical excipient (magnesium stearate). "The complex is just as effective, but more stable. It slowly releases the antibiotic on the spot," explains Mäder. "In addition to the continuous and sustained release of the antibiotic, we needed to find an easy way of administering it." His research group found a practical solution to this problem by utilising pharma-grade polymers. The researchers were able to use these chemical substances to produce flexible, biodegradable rods containing the antibiotic. The small rods can be easily inserted into the gingival pocket. Since they are broken down by the body, they do not have to be removed after treatment. "The rods are much more effective in vitro than previous products on the market," says Martin Kirchberg, who is studying the topic as part of his doctoral thesis. Among other things, Kirchberg has optimised the composition of the polymers in order to achieve exactly the right balance between strength and flexibility and to make them long-lasting. Development is already so advanced that large-scale production would be possible.

The patent for the complex active ingredient and its formulation was applied for together with the Fraunhofer Institute for Cell Therapy and Immunology IZI and the Fraunhofer Institute for Microstructure of Materials and Systems IMWS, both in Halle, as well as with the Clinic for Dental Medicine at the University of Bern. Mäder and Kirchberg each have a 30 % stake in the invention, with the remaining 40 % shared by scientists from the Fraunhofer Institutes in Halle and the University of Bern. Rapid implementation in clinical studies is possible since all of the pharmaceutical-grade ingredients are already available on the market. The rods can also be produced using proven techniques so that they can be market ready in just a few years' time. The further development of the formulation and its subsequent market launch will be carried out by PerioTrap Pharmaceuticals GmbH, a start-up company founded by Fraunhofer IZI in Halle.

The project was financially supported by the State of Saxony-Anhalt with funds from the European Regional Development Fund (ERDF) as part of the "Transfer and High-Performance Centre Chemical and Biosystems Technology"

By the second trimester, long before a baby's eyes can see images, they can detect light.

But the light-sensitive cells in the developing retina -- the thin sheet of brain-like tissue at the back of the eye -- were thought to be simple on-off switches, presumably there to set up the 24-hour, day-night rhythms parents hope their baby will follow.

University of California, Berkeley, scientists have now found evidence that these simple cells actually talk to one another as part of an interconnected network that gives the retina more light sensitivity than once thought, and that may enhance the influence of light on behavior and brain development in unsuspected ways.

In the developing eye, perhaps 3% of ganglion cells -- the cells in the retina that send messages through the optic nerve into the brain -- are sensitive to light and, to date, researchers have found about six different subtypes that communicate with various places in the brain. Some talk to the suprachiasmatic nucleus to tune our internal clock to the day-night cycle. Others send signals to the area that makes our pupils constrict in bright light.

But others connect to surprising areas: the perihabenula, which regulates mood, and the amygdala, which deals with emotions.

In mice and monkeys, recent evidence suggests that these ganglion cells also talk with one another through electrical connections called gap junctions, implying much more complexity in immature rodent and primate eyes than imagined.

"Given the variety of these ganglion cells and that they project to many different parts of the brain, it makes me wonder whether they play a role in how the retina connects up to the brain," said Marla Feller, a UC Berkeley professor of molecular and cell biology and senior author of a paper that appeared this month in the journal Current Biology. "Maybe not for visual circuits, but for non-vision behaviors. Not only the pupillary light reflex and circadian rhythms, but possibly explaining problems like light-induced migraines, or why light therapy works for depression."

Parallel systems in developing retina

The cells, called intrinsically photosensitive retinal ganglion cells (ipRGCs), were discovered only 10 years ago, surprising those like Feller who had been studying the developing retina for nearly 20 years. She played a major role, along with her mentor, Carla Shatz of Stanford University, in showing that spontaneous electrical activity in the eye during development -- so-called retinal waves -- is critical for setting up the correct brain networks to process images later on.

Hence her interest in the ipRGCs that seemed to function in parallel with spontaneous retinal waves in the developing retina.

"We thought they (mouse pups and the human fetus) were blind at this point in development," said Feller, the Paul Licht Distinguished Professor in Biological Sciences and a member of UC Berkeley's Helen Wills Neuroscience Institute. "We thought that the ganglion cells were there in the developing eye, that they are connected to the brain, but that they were not really connected to much of the rest of the retina, at that point. Now, it turns out they are connected to each other, which was a surprising thing."

UC Berkeley graduate student Franklin Caval-Holme combined two-photon calcium imaging, whole-cell electrical recording, pharmacology and anatomical techniques to show that the six types of ipRGCs in the newborn mouse retina link up electrically, via gap junctions, to form a retinal network that the researchers found not only detects light, but responds to the intensity of the light, which can vary nearly a billionfold.

Gap junction circuits were critical for light sensitivity in some ipRGC subtypes, but not others, providing a potential avenue to determine which ipRGC subtypes provide the signal for specific non-visual behaviors that light evokes.

"Aversion to light, which pups develop very early, is intensity-dependent," suggesting that these neural circuits could be involved in light-aversion behavior, Caval-Holme said. "We don't know which of these ipRGC subtypes in the neonatal retina actually contributes to the behavior, so it will be very interesting to see what role all these different subtypes have."

The researchers also found evidence that the circuit tunes itself in a way that could adapt to the intensity of light, which probably has an important role in development, Feller said.

"In the past, people demonstrated that these light-sensitive cells are important for things like the development of the blood vessels in the retina and light entrainment of circadian rhythms, but those were kind of a light on/light off response, where you need some light or no light," she said. "This seems to argue that they are actually trying to code for many different intensities of light, encoding much more information than people had previously thought."

Theoreticians in two different fields defied the common knowledge that planets orbit stars like the Sun. They proposed the possibility of thousands of planets around a supermassive black hole.

"With the right conditions, planets could be formed even in harsh environments, such as around a black hole," says Keiichi Wada, a professor at Kagoshima University researching active galactic nuclei which are luminous objects energized by black holes.

According to the latest theories, planets are formed from fluffy dust aggregates in a protoplanetary disk around a young star. But young stars are not the only objects that possess dust disks. In a novel approach, the researchers focused on heavy disks around supermassive black holes in the nuclei of galaxies.

"Our calculations show that tens of thousands of planets with 10 times the mass of the Earth could be formed around 10 light-years from a black hole," says Eiichiro Kokubo, a professor at the National Astronomical Observatory of Japan who studies planet formation. "Around black holes there might exist planetary systems of astonishing scale."

Some supermassive black holes have large amounts of matter around them in the form of a heavy, dense disk. A disk can contain as much as a hundred thousand times the mass of the Sun worth of dust. This is a billion times the dust mass of a protoplanetary disk.

In a low temperature region of a protoplanetary disk, dust grains with ice mantles stick together and evolve into fluffy aggregates. A dust disk around a black hole is so dense that the intense radiation from the central region is blocked and low temperature regions are formed. The researchers applied the planet formation theory to circumnuclear disks and found that planets could be formed in several hundred million years.

Currently there are no techniques to detect these planets around black holes. However, the researchers expect this study to open a new field of astronomy.

A study led by researchers at Monash University has opened up new hope for diagnosing and treating Alzheimer's disease.

Alzheimer's disease is the most common form of dementia in older people and, as there are no effective treatments, is one of the leading contributors to the global disease burden.

Various genes have been implicated in the changes that happen in the brains of Alzheimer's patients. What is not known is how the activity of the genes - called gene expression - affects the many different cells of the brain.

The study, led by Monash University's Professor Jose Polo, from the Monash Biomedicine Discovery Institute and the Australian Regenerative Medicine Institute, focused on how individual cell types in the brain contribute to Alzheimer's disease.

Through a series of complex tests, they looked at patterns in gene expression in specific cells and how changes in specific cell subpopulations are associated with Alzheimer's.

The researchers were excited to make a number of key discoveries into understanding Alzheimer's disease that require further study.

This included the role of disease gene networks, genes working together, in the human brain, pathways to genetic susceptibility, subcellular changes in areas of the brain, and the role of myelination in Alzheimer's disease pathogenesis.

The study was co-led with researchers from Duke-National University of Singapore and in collaboration with the University of Melbourne, Florey Institute, the University of Western Australia and the Harry Perkins Institute of Medical Research. This is an excellent outcome from the Monash International Network of Excellence program, that is designed to bring together new international teams working towards the solution of big problems.

In a paper published in Nature Neuroscience on Tuesday, November 26, the researchers said: "although our study contributes significantly to our understanding of the transcriptional changes underpinning changes in brain cells in Alzheimer's disease, examining larger patient cohorts in the future will enable assessment of the effects and relative contribution of underlying genetic factors to the described cellular and transcriptomic changes in disease.

"We anticipate that our resource will stimulate and allow further discoveries in many different areas, as exemplified by our work."

Professor Polo said the findings are an exciting step in eventually diagnosing and treating Alzheimer's disease.

"Alzheimer's disease is an increasingly prevalent cause of dementia in ageing societies like Australia and Singapore. Despite billions of funds poured in, an effective drug has yet to be discovered," the lead researchers said.

"In order to make advancements, there is a need to focus on other cell types in the brain aside from neurons - the main cell type in the brain.

A key researcher in the study, Dr Alexandra Grubman, from Monash University's Australian Regenerative Medicine Institute and a NHMRC-ARC Dementia Fellow, is excited at the new therapeutic possibilities the study has opened.

"Perhaps the answer to treating Alzheimer's lies in understanding how these non-neuronal cells are affected during disease," she said.

This multinational team will now conduct further research on genes that can potentially be treated with medical drugs.

The CRISPR/Cas technology can do more than alter genes. A research team at the University of Freiburg is using what are known as gene scissors - which scientists can use to edit genetic material - in order to better diagnose diseases such as cancer. In a study, the researchers introduce a microfluidic chip which recognizes small fragments of RNA, indicating a specific type of cancer more rapidly and precisely than the techniques available up to now. The results are recently published in the scientific journal "Advanced Materials." They also tested the CRISPR biosensor on blood samples taken from four children who had been diagnosed with brain tumors. "Our electrochemical biosensor is five to ten times more sensitive than other applications which use CRISPR/Cas for RNA analysis," explains Freiburg microsystems engineer Dr. Can Dincer. He is leading the research team together with biologist Prof. Dr. Wilfried Weber, of the University of Freiburg. "We're doing pioneering work in Germany and Europe for this new application of gene scissors," Dincer emphasizes.

Short molecules known as microRNA (miRNA) are coded in the genome, but unlike other RNA sequences, they are not translated into proteins. In some diseases, such as cancer or the neurodegenerative disease, Alzheimer's, increased levels of miRNA can be detected in the blood. Doctors are already using miRNAs as a biomarker for certain types of cancer. Only the detection of a multitude of such signaling molecules allows an appropriate diagnosis. The researchers are now working on a version of the biosensor that recognizes up to eight different RNA markers simultaneously.

The CRISPR biosensor works as follows: A drop of serum is mixed with reaction solution and dropped onto the sensor. If it contains the target RNA, this molecule binds with a protein complex in the solution and activates the gene scissors - in a way similar to a key opening a door lock. Thus activated, the CRISPR protein cuts off, or cleaves, the reporter RNAs that are attached to signaling molecules, generating an electrical current. The cleavage results in a reduction of the current signals which can be measured electrochemically and indicates if the miRNA that is being sought is present in the sample. "What's special about our system is that it works without the replication of miRNA, because in that case, specialized devices and chemicals would be required. That makes our system low-cost and considerably faster than other techniques or methods," explains Dincer. He is working on new sensor technologies at the Freiburg Center for Interactive Materials and Bioinspired Technologies (FIT) and together with Prof. Dr. Gerald Urban at the Department of Microsystems Engineering (IMTEK).

Weber, a professor of synthetic biology at the cluster of excellence CIBSS - the Centre for Integrative Biological Signalling Studies of the University of Freiburg - emphasizes how important the interdisciplinary environment at CIBSS is for such a development: "The biologists at Freiburg work together on these technologies with their colleagues from the engineering and materials sciences. That opens new, exciting routes to solutions." The researchers are aiming to further develop the system in about five to ten years to become the first rapid test for diseases with established microRNA markers that can be used right at the doctor's office. "The laboratory equipment must nevertheless become easier to handle," says Weber.

Nature has sentenced humans to an inevitable death from the time of birth; the natural instrument of execution is the aging process. According to modern scientific notions, only two root causes of aging can be: stochastic physiological damage or the implementation of a special genetic program in the body. The first supposition is dominated from the onset of gerontology to the present day. Indeed, experiments provide conclusive evidence that infections produce toxins, that mitochondria generate ROS which cause mutations in nuclear and mitochondrial DNA, that errors occur in the processes of DNA reduplication, transcription and translation, that lipid peroxidation occurs in membranes, that non-enzymatic glycolysis and crosslinking between molecules occurs, and more; all of this accumulates over time. These facts leave no doubt about the cause of aging and suggest the clear measures to combat it. Almost all experiments aimed at increasing the maximum longevity of animals are reduced ultimately to methods that involve the prevention or restoration of this damage. A lot of different approaches have been tried, but the maximum animal longevity has remained unshakable. These results testify unequivocally that the concept of stochastic physiological damages accumulation is incorrect and therefore the alternative concept of genetically programmed aging is true.

In support of this conclusion, in the last decade, convincing experimental evidence has been found that the aging process is under direct genetic control: dysfunction of a single gene can increase the maximum lifespan of animals (several times for some invertebrates). About 80 such genes have been identified to date. However, this way of prolonging life has proved unsuitable for human due to dangerous side effects. Currently, only unfounded assumptions have been made about the existence of a genetic aging program, but there is no explanation for many empirically discovered phenomena, including this life-extending effect.

A fundamentally new mechanism of programmed aging is presented in this article by Alexander G. Trubitsyn (Institute of Biology, Russian Academy of Sciences). The mechanism of programmed aging has turned out to be much more complicated than that of accumulation of stochastic physiological damages. The destructive stochastic processes that are observed by researchers serve as the mechanism of execution of aging program rather than its root cause which should be fought.

A special bioenergetics aging clock follows from this mechanism of programmed aging and some other empirical data as a logical consequence. This clock gives us an opportunity to clarify nature of the above mentioned empirically found methods of life extending. It is this clock that sets the maximum species-specific longevity. This clock enables us to interpret all discovered phenomena concerning aging and longevity: the nature of the life-lengthening effect under calorie restriction (CR) and numerous CR-mimetic factors. It gives us an opportunity to understand why a bat and a bird lives 10 times longer than a terrestrial animal of a similar size, and a naked mole-rat (Heterocephalus glaber) has an impressively longer longevity in comparison with a home mouse, the nature of negligible senescence of some species and why cancer cells are immortal, and so on.

Most importantly, this special aging clock opens up a fundamentally new way of searching the means to control the aging process. Fundamental research in the field of molecular biology and related areas has already discovered the basic details of this clock, although even the authors of these studies are mostly not aware of the role of their discoveries in the mechanism of programed aging. These data, gathered together, provide insights into the molecular structure and functioning of the bioenergetics aging clock. This makes it possible to outline practical research on the management of the course of this clock, and hence the longevity. Three possible approaches to modify the course of this clock are visible. A creation of actual remedy for senescence in the near future looks like a real possibility.

A study conducted at the VIB-KU Leuven Center for Cancer Biology discovered that healthy liver tissue surrounding a tumor activates a defence mechanism that restrains tumor growth. Remarkably, the researchers found that hyperactivation of this mechanism above levels normally present in the liver, triggered the elimination of different types of liver tumors in mice. This discovery identifies a novel strategy to fight against liver cancer and could inspire new therapeutic approaches that mobilize normal cells to kill cancer cells. The results of the study are published in Science.

Fighting tumors

Current chemotherapies aim at killing rapidly proliferating cancer cells. However, such therapies are often only temporarily effective because cancer cells quickly evolve drug resistance. Nowadays, other approaches such as immune therapy do not target tumor cells themselves but activate the natural defense function of the immune system.

The study, led by Prof. Georg Halder (VIB-KU Leuven Center for Cancer Biology), showed that not only the immune system but also non-cancerous liver cells around liver tumors have the capacity to kill nearby tumor cells. When they experimentally activated this novel mechanism in mice with liver tumors, these mice survived significantly longer and had a drastically reduced tumor burden.

Prof. Halder says: "While the study shows that this anti-tumor mechanism exists, how exactly activated liver cells cause the elimination of cancer cells is not known, but it is obviously a highly significant question that we are currently investigating."

Unexpected genes

By studying tumor tissues from cancer patients and mouse models for liver cancer, the scientists found that the genes YAP and TAZ were activated around tumors in the liver and that this was the driving force of the anti-tumor mechanism.

This observation was surprising because YAP and TAZ are usually highly expressed in different human cancers where they drive tumor cell proliferation and survival. "The identification of anti-tumor functions in genes traditionally considered as tumor promoting genes completely changes how we think about cancer genes and their function in normal tissues," says Iván Moya, first author of the paper.

Towards new therapies

While this study showed that this anti-tumor mechanism can kill tumors and metastases in the liver, it is not yet known whether similar mechanisms can be activated in other organs. "Given the striking anti?tumor effect of YAP?activated liver cells on liver tumors, our discovery has the potential to provide ground-breaking insights into a novel strategy to fight," says Stephanie Castaldo, co-first-author.

However, while this remarkable finding identifies a completely new strategy to fight cancer in mice, this study is the first molecular characterization of this novel anti-tumor mechanism which means that more research is needed to investigate how these findings can be applied to benefit cancer patients. "Indeed, the next step is to test to what degree this mechanism also affects human cancer cells," says Laura Van den Mooter, also co-first-author.

Reports of new cancer treatments often raise high hopes and expectations, particularly, of course, among cancer patients and their families. But raising expectations is not something that Samer Ezziddin, Professor of Nuclear Medicine and Director of the Department of Nuclear Medicine at Saarland University Hospital is keen to do. 'In most cases, we cannot heal the patients who take part in our therapeutic programme. Our aim is to extend life expectancy by a number of months or even years, without impairing the patients' quality of life,' explains Ezziddin. And although over the course of his career he has seen patients whose cancer has regressed completely despite extremely poor prognoses, such cases remain the exception and should be regarded as 'statistical outliers' rather than miracle cures. The battle to treat the many different varieties of cancer continues to be very challenging, involving careful but laborious work, where progress is measured in small steps and where significant advancements only become apparent after an extended period of time.

The current study from the team of nuclear radiologists in Saarland is also a small step, but one that could be decisive for future therapeutic approaches. The physicians subjected patients with advanced prostate cancer to a radiation therapy regimen that was originally developed in Heidelberg and that has now been developed further by the team in Saarland. The approach used is known as targeted radionuclide therapy. A radioactive drug injected into a patient's vein is continuously fed to the tumour site where the radioactive substance ('the radionuclide') irradiates the tumour internally, thus destroying the tumour cells.

But rather than injecting just one type of radioactive drug into the tumour, the medical research team in Saarland chose to combine two different radiopharmaceuticals each having a different irradiation path length. One of the radionuclides used was lutetium-177. This radioactive material has an effective range of 0.5 to 10 millimetres, which is the distance over which the surrounding tissue is destroyed. It is highly precise, because the radionuclide is attached to a cell-targeting molecule that only binds to receptor sites almost exclusively located on the surface of prostate tumours, leaving other healthy body cells unaffected. However, even the very short distance over which lutetium-177 is effective may be too great when treating the tiniest tumours that can form when the cancer spreads to other parts of the body. The research team led by Professor Ezziddin therefore decided to add a second radioactive nuclide, actinium-225, to their therapy regimen. Samer Ezziddin explains the benefits as follows: 'Actinium-225 delivers excellent results; its effective path length is well down in the sub-millimetre range.'

By including actinium-225 as a therapeutic agent even the smallest of tumours, in principle even individual tumour cells, can be irradiated internally once the radioactive substance has infiltrated the cancer cell via the receptor site. 'Because the effective path length of actinium-225 is only three to four cell diameters, surrounding tissue is not destroyed,' explains Professor Ezziddin. However, previous radionuclide therapies based on actinium-225 suffered from one crucial disadvantage. The patient's salivary glands can also take up the radionuclide, causing decreased function of the glands and resulting in extreme dryness in the mouth, which can significantly reduce the patient's quality of life.

The paper just published describes the results of a pilot study that examined the effectiveness of the tandem therapy proposed by the research team from Saarland University Hospital. The study was able to demonstrate that these side effects no longer occur when lutetium and actinium are combined in a specific therapy regimen. 'Lutetium is very well tolerated for most sizes of tumour,' explains Professor Ezziddin. 'This allowed us to significantly reduce the actinium dosage level, so that our tandem therapy can be carried out with very few side effects.'

The study analysed the experiences of 20 patients aged between 57 and 88 with late-stage or end-stage metastatic prostate cancer and whose tumours no longer responded to treatment using only lutetium-177. 'The patients in our study were already heavily pre-treated. Many of them had already been told that there was little that could be done,' says Samer Ezziddin. In 14 of the 20 cases, the team observed a substantial decrease in tumour marker levels while the patients were undergoing tandem therapy. (Tumour marker concentrations indicate how much tumour mass is still in body.) It was found that after starting tandem therapy, tumour growth could be stabilized for about four and a half months (median average value) before the disease progressed, and that survival after starting tandem therapy was 11 months (median value) without any substantial reduction in the patients' quality of life.

UNIVERSITY PARK, Pa. -- As it becomes more common for women to be the breadwinner of their family, men's health may be affected depending on their views on gender ideology, according to Penn State researchers.

The researchers found that men who were financially dependent on their wives and who also had more traditional beliefs about gender roles tended to have higher "allostatic loads," or wear and tear on the body as the result of stress.

Men who had more "egalitarian" or progressive views about gender seemed to be protected from this effect.

Joeun Kim, a doctoral candidate in sociology and demography, said the results -- recently published in the Journal of Marriage and Family -- are an example of how gender equality can benefit men as well as women.

"In a lot of discussions about gender equality, men are often left out of the conversation," Kim said. "But it's not just about women, it's about true equality across gender. Men are also bearing the burdens imposed by society, for example, the pressure to be the family breadwinner. We know that men tend to die earlier than women, and this research speaks to how we can help improve health measures."

The researchers said that while men being the main breadwinner of the family is an enduring social norm in the United States, the percentage of women earning more than 50% of their household's income rose from 16% in 1981 to almost 30% in 2017, according to the U.S. Census Bureau.

Previous research has found links between threats to masculinity and increased stress, which the researchers said could have myriad effects on health. While a former study also found connections between male unemployment and stress, the researchers were curious about whether men's financial dependency on women would have a similar effect.

The researchers used data about 348 heterosexual males who were married to or cohabitating with women. Data was collected on the men's health and ideologies about gender, as well as details about the households' income. Ideologies were measured by asking the participants how much they agreed with the statements "men should equally share housework" and "men should equally share child care."

Saliva, blood and urine samples were also used to calculate the participants' allostatic load, which Kim explained is a biological indicator of wear and tear on the body that happens as a result of chronic stress.

"Previous studies have found that if you going through adverse experiences like poverty as a child, you have higher allostatic load as an adult," Kim said. "It's measured through several biomarkers, and combining that information gives you an allostatic load score. It's helpful to have biological data, because men often underreport their symptoms in health studies."

After analyzing the data, the researchers found that there was no general association between men having partners who make more money than they do and a higher allostatic load. But, when the researchers took into account the men's beliefs about gender roles, they found that more traditional views were linked to higher allostatic load.

"This may speak to the implications that female breadwinning may be threatening in a way that could potentially impact health, depending on a person's ideas about gender roles," Kim said. "When we talk about gender equality, I think it's important to remember to include men in the discussion, because these issues affect them, as well."

Kim said that because studies have shown that higher allostatic load can contribute to the development of chronic diseases such as diabetes, coronary heart disease, dementia and higher mortality risk, future research could explore ways to reduce these risks.