Culture

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.

CHAMPAIGN, Ill. -- Research from the University of Illinois and the University of California, Davis has chemists one step closer to recreating nature's most efficient machinery for generating hydrogen gas. This new development may help clear the path for the hydrogen fuel industry to move into a larger role in the global push toward more environmentally friendly energy sources.

The researchers report their findings in the Proceedings of the National Academy of Sciences.

Currently, hydrogen gas is produced using a very complex industrial process that limits its attractiveness to the green fuel market, the researchers said. In response, scientists are looking toward biologically synthesized hydrogen, which is far more efficient than the current human-made process, said chemistry professor and study co-author Thomas Rauchfuss.

Biological enzymes, called hydrogenases, are nature's machinery for making and burning hydrogen gas. These enzymes come in two varieties, iron-iron and nickel-iron - named for the elements responsible for driving the chemical reactions. The new study focuses on the iron-iron variety because it does the job faster, the researchers said.

The team came into the study with a general understanding of the chemical composition of the active sites within the enzyme. They hypothesized that the sites were assembled using 10 parts: four carbon monoxide molecules, two cyanide ions, two iron ions and two groups of a sulfur-containing amino acid called cysteine.

The team discovered that it was instead more likely that the enzyme's engine was composed of two identical groups containing five chemicals: two carbon monoxide molecules, one cyanide ion, one iron ion and one cysteine group. The groups form one tightly bonded unit, and the two units combine to give the engine a total of 10 parts.

But the laboratory analysis of the lab-synthesized enzyme revealed a final surprise, Rauchfuss said. "Our recipe is incomplete. We now know that 11 bits are required to make the active site engine, not 10, and we are in the hunt for that one final bit."

Team members say they are not sure what type of applications this new understanding of the iron-iron hydrogenase enzyme will lead to, but the research could provide an assembly kit that will be instructive to other catalyst design projects.

"The take-away from this study is that it is one thing to envision using the real enzyme to produce hydrogen gas, but it is far more powerful to understand its makeup well enough to able to reproduce it for use in the lab," Rauchfuss said.

Researchers from the Oregon Health and Science University also contributed to this study.

The air, earth and water of our planet are pulsating with living things. Yet, a vast and diverse web of life exists, about which almost nothing is known. This is the world of flagellates, tiny organisms that persist in staggering numbers in many diverse ecosystems around the world.

According to Jeremy Wideman, a researcher at the Biodesign Center for Mechanisms in Evolution at Arizona State University, we have a great deal to learn from these delicate and wildly varied creatures. Among other surprises, flagellates could provide valuable clues about a shadowy event that may have occurred 1.5-2 billion years ago, (no one is really sure of the timing), with the arrival of a new type of cell.

Known as LECA, it was a sort of primal egg out of which the astonishing profusion of complex life--from flagellate organisms, fungi and plants, to insects, zebra, and humans, exploded and spread over the earth.

In new research appearing today in the journal Nature Microbiology, Wideman and his colleagues, including Prof. Thomas Richards at the University of Exeter describe a new method for investigating the genomes of eukaryotic flagellate organisms, which have been notoriously tricky to pinpoint and sequence.

Specifically, they explored samples of mitochondrial DNA, sequencing around 100 such genomes for previously undocumented flagellates. The new technique could help scientists like Wideman begin to fill in the largely blank region of the eukaryotic puzzle, where flagellate life flourishes.

Cellular worlds

Wideman, originally a traditional cell biologist, became frustrated with the many unaddressed questions in the field, recently joining the emerging discipline of evolutionary cell biology. This rapidly advancing research area uses cells as fundamental units for the study of evolutionary processes and imports concepts from evolutionary biology to better understand how cells work. "I'm literally a cell biologist that wants to know more about things we know nothing about," he says.

Evolutionary cell biology is a profoundly transdisciplinary endeavor, fusing evolutionary theory, genomics and cell biology with quantitative branches of biochemistry, biophysics, and population genetics.

Flagellates include many parasites implicated in human disease, from the intestinal bug Giardia to more damaging trypanosomes, and leishmania. Flagellates also perform more benevolent tasks. As the major consumers of bacteria and other protists in aquatic ecosystems, they help ensure the recycling of limiting nutrients.

Single-celled eukaryotic organisms, which include flagellates, constitute the overwhelming majority of eukaryotic diversity, vastly outpacing the more familiar multicellular plants, animals, and fungi. Despite their importance and ubiquity across the globe, flagellates are, as Wideman stresses, an almost entirely unknown inhabitant of the living world and one of the most enigmatic. When viewed under a microscope, their often science fiction-like appearance is markedly distinct from the kinds of eukaryotic cells commonly described in biology textbooks. Their emergence from comparatively rudimentary prokaryotes marks the most momentous transition in the history of life on earth.

"Novel lineages of heterotrophic flagellates are being discovered at an alarming, rate," Wideman says. "In the last two years 2 kingdom level lineages have been discovered (see here and here), meaning lineages that have been evolving independently of animals and fungi for over a billion years." Nevertheless, researchers have barely scratched the surface of this astonishing diversity and new methods must be brought to bear to speed up the quest. (Heterotrophs are organisms that cannot synthesize their own food, relying instead on other organisms for nutrition.)

Microbial safari

Any drop of pond, lake or ocean water is likely to contain many flagellates, but separating them from a multitude of non-flagellates and accurately reading their genomes by conventional means has been slow and painstaking work. Only a minute fraction of extant flagellates have known genomic sequences and it's even possible that the overwhelming majority have never actually been seen. According to Wideman, flagellate life forms represent the 'dark matter' of the eukaryotic universe.

"Heterotrophic flagellates are the target," Wideman says. "They're not a lineage. They're many, many lineages that are from all over the tree of life. LECA, the Last Eukaryotic Common Ancestor, was a heterotrophic flagellate, which means, that every major lineage (of eukaryotes) evolved from some sort of heterotrophic flagellate."

To access the elusive flagellate mitochondrial DNA, the researchers exploited a feature common to all flagellates and from which they take their name--the existence of flagella, which, unlike in animal sperm are on the front of cells and are often used to pull them forward like a microscopic breast stroke but are also involved in sensation, feeding, and perhaps other, as-yet unknown functions.

Flagella are rich in a particular protein known as tubulin. The new method for identifying flagellates and distinguishing them from their aquatic neighbors--primarily algae and bacteria--capitalizes on this fact by applying a selective stain to flagella-bearing organisms, activated by their high tubulin content. (Algal cells are naturally marked by their chloroplasts, which the flagellates of interest in the new study lack.)

Samples of sea water collected in 2014 off the coast of California provided a test case. Using the technique, the researchers gathered a windfall of mitochondrial sequence data, significantly expanding the catalog of flagellates identified by molecular means. Indeed, they doubled the existing mitochondrial DNA library for flagellate organisms. "We got many, many different kinds of organisms. So it was a very rich sample and very few were identical," Wideman says.

In search of LECA

Apart from the mystery of life's origin, the puzzle of where eukaryotes came from and how the LECA event transpired is the most important and vexing unanswered question in all of biology. (It has been dubbed the black hole at the heart of the living world.)

Correctly establishing the sequence of events underlying the crucial innovations within eukaryotes, from whence all complex life sprang, will take much more research in unexplored regions of the existing eukaryotic domain, particularly, the flagellates. Wideman believes the rapid advance of techniques for identifying and sequencing these organisms, such as the one outlined in the new study, offer hope such questions may one day find answers.

CHAMPAIGN, Ill. -- When they share habitat, orangethroat and rainbow darters tend to avoid one another, even though they are closely related and can produce "hybrid" offspring. The males compete with males of their own species and will almost always ignore females of the other species. A new study offers an analysis of the genomic changes that occur when these fish hybridize, offering insight into the gradual accumulation of incompatible traits that likely drives them to diverge.

The researchers report their findings in the journal Molecular Biology and Evolution.

Scientists have spent decades trying to understand the factors that allow closely related organisms to evolve into separate species, said Becky Fuller, a University of Illinois professor of evolution, ecology and behavior who led the research with study lead author Rachel Moran. Now a postdoctoral researcher at the University of Minnesota, Moran conducted the research as a graduate student in Fuller's lab.

The most obvious driver of speciation is geographic isolation, but other factors also contribute, Fuller said.

"For example, two populations may randomly develop anatomical or physiological differences that prevent them from successfully mating with one another," she said.

Other behavioral and genomic changes that contribute to species divergence are subtler and more difficult to track, Moran said.

"We were particularly interested in comparing the orangethroat darter with the rainbow darter because the two species co-occur and can form hybrids," she said. "Interspecies mating is costly for these fish, as it does not result in healthy offspring."

If the offspring die, they fail to pass their genetic heritage to the next generation. Those lineages with a proclivity for interspecies mating gradually die out.

"Consequently, when the two species co-occur in the same habitat, they evolve strong preferences to mate with their own species and ignore the other species," Moran said.

To understand how genomic factors influence this process, the researchers mated orangethroat and rainbow darters in the lab and analyzed the genomes of the few hybrid offspring that survived past hatching. They sequenced the genome of the orangethroat darter and conducted a series of analyses to determine which regions of the two species were misaligned.

"We found that areas of the genome that had a lot of genetic divergence between the two species likely contributed to their reproductive incompatibility," Moran said. These differences are widespread and include problematic variations in the sequence and order of genes on the chromosomes.

The differences would likely disrupt cell division and could alter gene expression in hybrid offspring, Fuller said.

"This study opens a window on the post-reproductive mechanisms that contribute to the evolution of differing traits in closely related species," Fuller said.

"How species that exchange genetic material through hybridization are able to coexist and remain distinct from one another has puzzled evolutionary biologists for decades," Moran said. "The insights we've gained from this study have hopefully gotten us a little closer to answering that big question."