Culture

Researchers have devised a straightforward technique for building a laboratory device known as an electroporator - which applies a jolt of electricity to temporarily open cell walls - from inexpensive components, including a piezoelectric crystal taken from a butane lighter.

The goal would be to make the low-cost device available to high schools, budget-pressed laboratories and other organizations whose research might otherwise be limited by access to conventional lab-grade electroporators. Plans for the device, known as the ElectroPen, are being made available, along with the files necessary for creating a 3D-printed casing

"Our goal with the ElectroPen was to make it possible for high schools, budget-conscious laboratories and even those working in remote locations without access to electricity to perform experiments or processes involving electroporation," said M. Saad Bhamla, an assistant professor in Georgia Tech's School of Chemical and Biomolecular Engineering. "This is another example of looking for ways to bypass economic limitations to advance scientific research by putting this capability into the hands of many more scientists and aspiring scientists."

In a study to be reported January 9 in the journal PLOS Biology and sponsored by the National Science Foundation and the National Institutes of Health, the researchers detail the method for constructing the ElectroPen, which is capable of generating short bursts of more than 2,000 volts needed for a wide range of laboratory tasks.

One of the primary jobs of a cell membrane is to serve as a protective border, sheltering the inner workings of a living cell from the outside environment.

But all it takes is a brief jolt of electricity for that membrane to temporarily open and allow foreign molecules to flow in -- a process called electroporation, which has been used for decades in molecular biology labs for tasks ranging from bacterial detection to genetic engineering.

Despite how commonplace the practice has become, the high cost of electroporators and their reliance on a source of electricity has kept the technique mostly within the confines of academic or professional labs. Bhamla and undergraduate student Gaurav Byagathvalli set out to change that, with help from collaborators Soham Sinha, Yan Zhang, Assistant Professor Mark Styczynski and Lambert High School teacher Janet Standeven.

"Once we decided to tackle this issue, we began to explore the inner workings of electroporators to understand why they are so bulky and expensive," said Byagathvalli. "Since their conception in the early 1980s, electroporators have not had significant changes in design, sparking the question of whether we could achieve the same output at a fraction of the cost. When we identified a lighter that could produce these high voltages through piezoelectricity, we were excited to uncover new mysteries behind this common tool."

In addition to the piezoelectric lighter crystal - which generates current when pressure is applied to it - the other parts in the device include copper-plated wire, heat-shrinking wire insulator and aluminum tape. To hold it all together, the researchers designed a 3D-printed casing that also serves as its activator. With all the parts on hand, the device can be assembled in 15 minutes, the researchers reported.

While the ElectroPen is not designed to replace a lab-grade electroporator, which costs thousands of dollars and is capable of processing a broad range of cell mixtures, the device is still highly capable of performing tasks when high volumes are not required.

The researchers tested several different lighter crystals to find ones that produced a consistent voltage using a spring-based mechanism. To understand more about how the lighters function, the team used a high-speed camera at 1,057 frames-per-second to view their mechanics in slow motion.

"One of the fundamental reasons this device works is that the piezoelectric crystal produces a consistently-high voltage, independent of the amount of force applied by the user," Bhamla said. "Our experiments showed that the hammer in these lighters is able to achieve acceleration of 3,000 Gs, which explains why it is capable of generating such a high burst of voltage."

To test its capabilities, the researchers used the device on samples of E. coli to add a chemical that makes the bacterial cells fluorescent under special lights, illuminating the cell parts and making them easier to identify. Similar techniques could be used in a lab or in remote field operations to detect the presence of bacteria or other cells.

The team also evaluated whether the device was easy to use, shipping the assembled ElectroPens to students at other universities and high schools.

"The research teams were able to successfully obtain the same fluorescence expression, which I think validates how easily these devices can be disseminated and adopted by students across the globe," Bhamla said.

To that end, the researchers have made available the plans for how to build the device, along with digital files to be used by a 3D printer to fabricate the casing and actuator. Next steps of the research include testing a broader range of lighters looking for consistent voltages across a wider range, with the goal of creating ElectroPens of varying voltages.

The flight navigation strategy of moths can be used to develop programs that help drones to navigate unfamiliar environments, report Ioannis Paschalidis at Boston University, Thomas Daniel at University of Washington, and colleagues, in the open-access journal PLOS Computational Biology.

To understand how real moths plan their route, the researchers mounted 8 hawk moths (Mantuca sexta) on metal rods connected to a torque meter. In front of each moth they projected a moving forest scene created from beams of light for the moth to navigate. They captured data from the moth flight and built a mathematical model to describe the moth trajectory through the virtual forest. The flight data were translated into a decision-making program that could be used to control a drone. They compared how the drone and the moth performed in simulations of the same forest layout, as well as new configurations with different densities of trees.

The researchers found that hawk moths mainly rely on the pattern created by the apparent motion of objects caused by their flight, which agrees with studies of flight behavior in other insects. However, the flight programs optimized for drones performed 60% better in the simulated forest because they also incorporated information about the exact location of objects in their surroundings into their navigational decisions.

Although the researchers were able to optimize the strategy used by moths to improve performance in certain environments, the moths' strategy was more adaptable, performing well in a variety of different forest layouts. The moth model performed best in dense forests, suggesting that hawk moths have evolved a flight strategy adapted to the thick forests they often encounter.

The researchers say that by using real data from animal flight paths they can program bio-inspired drones that will be able to navigate autonomously in cluttered environments.

The small red planet is losing water more quickly than what theory as well as past observations would suggest. The gradual disappearance of water (H2O) occurs in the upper atmosphere of Mars: sunlight and chemistry disassociate water molecules into hydrogen and oxygen atoms that the weak gravity of Mars cannot prevent from escaping into space. An international research team,1 led partly by CNRS researcher Franck Montmessin, has just revealed that water vapour is accumulating in large quantities and unexpected proportions at an altitude of over 80 km in the Martian atmosphere. Measurements showed that large atmospheric pockets are even in a state of supersaturation, with the atmosphere containing 10 to 100 times more water vapour than its temperature should theoretically allow. With the observed supersaturation rates, the capacity of water to escape would greatly increase during certain seasons. These results, which were published in Science on 9 January 2020, were obtained thanks to the Trace Gas Orbiter probe from the ExoMars mission, financed by the European Space Agency and the Russian space agency Roscosmos.

The ongoing social unrest in Hong Kong may be affecting the mental health of the general adult population--potentially leading to substantial increases in demand for mental and psychosocial support services, according to a 10-year observational study published in The Lancet.

The new estimates obtained from surveys suggest that the prevalence of probable depression [1] (in Hong Kong residents aged 18 years or more) was five times higher during the 2019 social unrest than the general population norm before the 2014 Occupy Central Movement (11% vs 2%); whilst post-traumatic stress disorder (PTSD) symptoms were estimated to be six times higher (rising from around 5% shortly after Occupy Central in March 2015 to almost 32% in Sept-Nov, 2019).

Even though less than half of those affected by health problems related to the social unrest said they would seek professional help, the authors estimate that mental health-care providers should prepare for potentially a 12% rise in demand for public sector services, which will require major increases in the surge capacity of these services.

"Hong Kong is under-resourced to deal with this excess mental health burden", explains Professor Gabriel Leung from The University of Hong Kong who co-led the research. "With only around half the per-capita psychiatry capacity of the UK, and pre-existing average public sector outpatient waiting times of up to 64 weeks, it is important that we enhance mental health and social care provision so that all those in need are able to access high-quality services." [2]

The study is the largest and longest prospective cohort study of the population-wide impact of social unrest on mental health in the world. However, the researchers caution that measuring the impact of mental health due to social unrest has several data and methodological issues that might affect the accuracy of the estimates, including the potential measurement error of assessment tools for depression and PTSD, and the many assumptions around care-seeking behaviour, psychopathology, and the duration and disposition of the ongoing social unrest.

Hong Kong has experienced a wave of mass protests since June 2019, initiated by the now shelved extradition bill. Over the course of 7 months, peaceful protests have descended into escalating levels of violence. Depressive and PTSD symptoms have been reported following widespread unrest worldwide, including after the 2014 Ferguson unrest and the 2015 Baltimore unrest in the USA. However, little is known about the mental health impact on the general population during recent protests in Hong Kong.

Researchers at The University of Hong Kong used the large population-based FAMILY Cohort with nine successive waves of longitudinal data to assess the population mental health burden before, during, and after major protests over 10 years [3]. The findings of two initial surveys (March 2009-April 2011 and Aug 2011-March 2014) involving more than 18,000 randomly sampled Hong Kong residents were compared with a representative sample of 1,213-1,715 adults surveyed five times during and following the Occupy Central Movement (Oct and Nov, 2014; March and Nov, 2015; Sept 2017), and 1,600-1,736 adults surveyed two times during the 2019 social unrest (June-Aug and Sept-Nov, 2019).

Questionnaires were used to measure changes in the prevalence of probable major depression, suspected PTSD (which included direct exposure to traumatic events such as tear gas or physical violence), and symptoms of depression and PTSD. The researchers used a weighted prevalence approach such that the rate of probable depression and suspected PTSD in the adults surveyed would be more representative of all adults in Hong Kong.

The study also examined risk factors associated with social unrest (after adjusting for socio-demographics and doctor-diagnosed depression or anxiety disorders before the 2019 unrest), and estimated potential health-care needs.

One in five Hong Kong residents (22%; aged 18 or older) surveyed during the 2019 social unrest reported probable major depression or suspected PTSD. The authors say that this is comparable to the prevalence of mental health conditions observed following large-scale disasters, armed conflicts, or terrorist attacks.

Estimates suggest that up to 11% of the adult general population in 2019 were affected by probable depression compared to around 2% in 2009-2014 before the 2014 Occupy Central Movement, and 6.5% in 2017 (figure 2)--potentially equivalent to an additional 590,000 adults with probable depression compared to a decade ago, with an estimated 300,000 of these cases potentially linked to the 2019 unrest (figure 3C).

Similarly, symptoms of PTSD were reported by an estimated 2% of adults in November, 2015 (a year after Occupy Central), rising to almost 32% of those surveyed in September-November, 2019--and could be equivalent to an additional 1.9 million adults with PTSD symptoms.

During the 2019 social unrest, the researchers estimate that the prevalence of suspected PTSD was around 13%--equivalent to around 810,000 adults with PTSD (figure 3A).

Adults using social media for two hours or more a day on socio-political news and events appear to be more at risk of probable depression and suspected PTSD, the findings suggest. However, family support seemed to protect against probable depression, potentially acting as a buffer against stress (figures 4 & 5).

Whilst fewer than half of those affected said they would seek help from health-care professionals--citing a preference for self-management, seeking help from family or friends, and privacy concerns among others--the researchers estimate that the 2019 social unrest may be associated with an additional 140,000 adults seeking outpatient support services for depression, and roughly 360,000 adults looking for help with PTSD (figure 3C).

The authors acknowledge that their findings provide observational associations rather than cause and effect, and point to several limitations of their study, including that the true population burden may be underestimated because they did not account for individuals younger than 18 years old who make up a substantial proportion of protesters, and did not specially oversample members of the police force. They also note that probable depression or suspected PTSD might represent psychological distress in response to an abnormal event rather than true mental illness.

"With social unrest rising around the world, including in major cities such as Barcelona, Delhi, Paris, and Santiago in 2019, the issue of how social unrest impacts population mental health is of great public-health importance," says Dr Michael Ni from The University of Hong Kong who co-led the research. [2]

"We hope our study will alert health-care professionals, service planners, and policy makers to the need for mental health and psychosocial support during and after widespread unrest to better protect population mental health globally," adds co-author Ms Cynthia Yau from The University of Hong Kong. [2]

Plant life is expanding in the area around Mount Everest, and across the Himalayan region, new research shows.

Scientists used satellite data to measure the extent of subnival vegetation - plants growing between the treeline and snowline - in this vast area.

Little is known about these remote, hard-to-reach ecosystems, made up of short-stature plants (predominantly grasses and shrubs) and seasonal snow, but the study reveals they cover between 5 and 15 times the area of permanent glaciers and snow.

Using data from 1993 to 2018 from NASA's Landsat satellites, University of Exeter researchers measured small but significant increases in subnival vegetation cover across four height brackets from 4,150-6,000 metres above sea level.

Results varied at different heights and locations, with the strongest trend in increased vegetation cover in the bracket 5,000-5,500m.

Around Mount Everest, the team found a significant increase in vegetation in all four height brackets. Conditions at the top of this height range have generally been considered to be close to the limit of where plants can grow.

Though the study doesn't examine the causes of the change, the findings are consistent with modelling that shows a decline in "temperature-limited areas" (where temperatures are too low for plants to grow) across the Himalayan region due to global warming.

Other research has suggested Himalayan ecosystems are highly vulnerable to climate-induced vegetation shifts.

"A lot of research has been done on ice melting in the Himalayan region, including a study that showed how the rate of ice loss doubled between 2000 and 2016," said Dr Karen Anderson, of the Environment and Sustainability Institute on Exeter's Penryn Campus in Cornwall.

"It's important to monitor and understand ice loss in major mountain systems, but subnival ecosystems cover a much larger area than permanent snow and ice and we know very little about them and how they moderate water supply.

"Snow falls and melts here seasonally, and we don't know what impact changing subnival vegetation will have on this aspect of the water cycle - which is vital because this region (known as 'Asia's water towers') feeds the ten largest rivers in Asia."

Dr Anderson said "some really detailed fieldwork" and further validation of these findings is now required to understand how plants in this high-altitude zone interact with soil and snow.

Dominic Fawcett, who coded the image processing, said: "These large-scale studies using decades of satellite data are computationally intensive because the file sizes are huge. We can now do this relatively easily on the cloud by using Google Earth Engine, a new and powerful tool freely available to anyone, anywhere."

The Hindu Kush Himalayan region extends across all or part of eight countries, from Afghanistan in the west to Myanmar in the east. More than 1.4 billion people depend on water from catchments emanating here.

The paper, published in the journal Global Change Biology, is entitled: "Vegetation expansion in the subnival Hindu Kush Himalaya."

RICHLAND, Washington -- A protein newly identified as important in type 1 diabetes can delay onset of the disease in diabetic mice, providing a new target for prevention and treatment in people, according to research led by scientists at the U.S. Department of Energy's Pacific Northwest National Laboratory and Indiana University School of Medicine. Because type 1 diabetes is incurable and has serious lifelong health consequences, prevention is a major research goal.

The key to the new study, published online January 9, 2020, in the journal Cell Metabolism, is a technique called mass spectrometry, which can comprehensively detect proteins that are found at extremely low levels in the body, but can have large effects on health.

The multidisciplinary research team of physicians and biochemists used a new strategy to pinpoint proteins in beta cells, a subset of pancreatic islets that increase or decrease in response to immune system attack. Beta cells normally regulate blood sugar levels in the pancreas. In people susceptible to type 1 diabetes (previously called insulin-dependent or juvenile diabetes) these cells are slowly destroyed by the body's own immune system. Here, the researchers focused on how islets respond to inflammation.

The researchers treated human pancreatic islets with substances produced by the body and thought to be involved in the diabetes disease process. They identified a total of 11,324 proteins, with 387 affected by the treatment. Of these 387, they narrowed their focus to one: growth differentiation factor 15 (GDF15).

"We wanted to identify proteins that can intervene in the diabetes disease process," said Ernesto Nakayasu, a biomedical scientist at PNNL and co-lead author of the study. "We became interested in GDF15 because the protein level was suppressed by 70 percent after treatment."

GDF15 is known for its protective effects in different types of cells in the human body but it had never been studied in islets. When the researchers measured levels of GDF15 in pancreas tissue from people with diabetes, they found the protein was depleted in their malfunctioning islet cells.

But the key piece of evidence emerged when the scientists treated non-obese diabetic mice with GDF15, and it reduced development of diabetes by 53%. Non-obese diabetic mice are a common model for testing type 1 diabetes treatments because they spontaneously develop autoimmune diabetes with many similarities to the human disease.

"We hypothesized that reduced GDF15 was not a good thing for islet survival, and indeed that was the case," said Raghu Mirmira, a study principal investigator. "This work opens the way for us to consider these sorts of 'islet protective factors' as therapies to prevent or reverse type 1 diabetes." Mirmira until recently served as professor of pediatric diabetes and director of the Center for Diabetes and Metabolic Diseases at Indiana University School of Medicine. He is now a professor of medicine in the Section of Endocrinology, Diabetes & Metabolism at the University of Chicago.

"This approach differs substantially from current thinking that targets the immune system. While GDF15 may be one new therapy, we identified other proteins that may work in conjunction with GDF15, so this work really represents a treasure-trove of information that can be mined for new therapies," said Mirmira.

PNNL's Tom Metz, the co-principal investigator and an expert in mass spectrometry-based proteomics of islets, agreed, adding, "This study illustrates the power of non-reductionist, comprehensive approaches, such as proteomics, for discovering new information in complex systems. The protective role of GDF15 against islet destruction and its ability to delay onset of type 1 diabetes in the mouse model would have been very difficult to discover without performing the initial comprehensive proteomics analysis of stressed human islets."

The researchers are now working on the idea that low levels of GDF15 in islets may somehow be playing a proactive role in instigating the autoimmune attack that ultimately kills them.

"This thinking is somewhat counterintuitive in the type 1 diabetes field, but it is this kind of out-of-the-box thinking that may lead to therapies we never thought of previously," said Mirmira.

Scientists could soon better investigate the feeding behaviors of extinct dolphin and whale species. A third year student at Japan's Nagoya University has found that the range of motion offered by the joint between the head and neck in modern-day cetaceans, a group of marine mammals that also includes porpoises, accurately reflects how they feed. The authors of the study, published in the Journal of Anatomy, suggest this method could help overcome current limitations in extrapolating the feeding behaviors of extinct cetaceans.

Taro Okamura of Nagoya University and Shin-ichi Fujiwara of the Nagoya University Museum examined the skulls and cervical skeletons of 56 cetaceans that are still in existence, representing 30 different species. They assessed the range of motion of the 'atlanto-occipital joint' in each skeleton, a joint that forms between the base of the skull and the first cervical vertebra. They then categorized each cetacean according to their well-studied feeding behaviors, including how they approach their prey, move it within their oral cavities, and swallow it.

"We found that the range of neck-head flexibility strongly reflects the difference of feeding strategies among whales and dolphins," says Okamura. "This index can be easily applied to reconstruct the feeding strategies of extinct whales and dolphins," he adds.

Cetaceans are known for their diverse behaviors, physiologies, ecologies and diets. Some cetaceans feed on organisms in the open water, while others feed on those found near the ocean floor. Some whales are ram feeders, widely opening their mouths to gather zooplankton and other actively swimming organisms into their mouths while moving forward. Other whales, like the sperm whale, suction their prey into their oral cavities. The orca whale and some dolphins bite the fish they catch into smaller segments, a process that may require head movement. Other dolphins swallow their prey whole.

Until now, scientists have used the structures of teeth, throat bones and lower jaws in cetacean fossils to develop an idea of what their feeding behaviors might have looked like. But these individual features can't accurately predict the behaviors of extinct cetaceans. For example, the teeth of some suction feeders, like those of the sperm whale, aren't suggestive of this kind of feeding. Okamura and Fujiwara propose that using a combination of features, which include the range of motion of the atlanto-occipital joint, could help to develop more accurate descriptions of extinct cetacean feeding behaviors.

In prehistoric times, many different types of cetaceans existed, including ones with walrus-like tusks, extremely long snouts, and an ancient sperm whale with huge predatory teeth. The ancient baleen whale had teeth, whereas modern-day baleen whales have 'baleen,' or fringed plates, in their place. This has created much interest in how baleen whale feeding, for example, has evolved from catching prey with teeth to filtering it with baleen.

The two researchers next plan to determine the atlanto-occipital joint range of motion in some of these cetacean fossils to attempt to develop reconstructions of how they used to feed. Answering these questions could help reveal the evolutionary process of the diverse feeding behaviors among cetaceans.

In a world first, University of Sydney researchers have found evidence of how hydrogen causes embrittlement of steels. When hydrogen moves into steel, it makes the metal become brittle, leading to catastrophic failures. This has been one of the major challenges in moving towards a greener, hydrogen-fuelled future, where steel tanks and pipelines are essential components that must be able to survive in pure hydrogen environments.

Published in Science, the researchers found hydrogen accumulates at microstructures called dislocations and at the boundaries between the individual crystals that make up the steel.

This accumulation weakens the steel along these features, leading to embrittlement.

The researchers also found the first direct evidence that clusters of niobium carbide within the steel trap hydrogen in such a way that it cannot readily move to the dislocations and crystal boundaries to cause embrittlement. This effect has the potential to be used to design steels that can resist embrittlement.

Lead researcher Dr Yi-Sheng Chen from the Australian Centre for Microscopy and Microanalysis and Faculty of Engineering at the University of Sydney said these findings were an important step to finding a safe solution to produce, store and transport hydrogen.

"These findings are vital for designing embrittlement-resistant steel; the carbides offer a solution to ensuring high-strength steels are not prone to early fracture and reduced toughness in the presence of hydrogen," Dr Chen said.

Senior author Professor Julie Cairney from the Australian Centre for Microscopy and Microanalysis and Faculty of Engineering at the University of Sydney said these findings were a positive step towards implementing clean fuels.

"Hydrogen is a low carbon fuel source that could potentially replace fossil fuels. But there are challenges with the use of steel, the world's most important engineering material, to safely store and transport it. This research gives us key insights into how we might be able to improve this situation," Professor Cairney said.

Working in partnership with CITIC Metal, the researchers were able to directly observe hydrogen at microstructures in steels thanks to Microscopy Australia's state-of-the-art custom-designed cryogenic atom probe microscope.

When a non-scientist tries to imagine a scientist, the image that often arises is one of a somewhat remote, rather idealistic genius sitting alone in their room or laboratory and somehow discovering the most amazing things without every having contact with the 'normal' world. But science is just as much a part of life as any other activity. So it's perhaps not all that surprising to learn that - just like in normal life - intuition can occasionally play a major role in scientific progress.

The importance of intuition was made very clear to Professor Samer Ezziddin and his team at the Department of Nuclear Medicine at Saarland University when they followed up on findings made during their medical research work into the treatment of patients with late-stage prostate cancer. The work centres around two receptors on the surface of the tumour. The first is known as prostate-specific membrane antigen (PSMA), a protein molecule that is very prevalent on the surface of prostate tumours. This surface receptor molecule acts as a gateway and provides a channel through which nuclear radiologists can smuggle radioactive substances into the tumour cells and thus destroy these malignant cells from the inside. The more PSMA molecules on the surface, the more radioactivity can be introduced into the cells without needing to increase the total dosage of radioactive substance being administered to the patient.

The second type of receptor is one that male sex hormones, such as testosterone, are able to dock onto. 'Prostate tumours need testosterone like a car needs petrol,' explains Professor Ezzidin. So one of the therapies used to treat prostate cancer involves blocking these receptor sites, which effectively stops the cancer from refuelling. 'One of the drugs used to block these receptors is enzalutamide and enzalutamide therapy is often very successful for a certain period of time, during which the tumour shrinks,' says Samer Ezzidin. 'But after a while - which might be several months, perhaps even two years if things go well - the drug stops working and the tumour starts to grow again.' Typically, the patient will then be taken off the expensive medication, as there would seem to be no reason to continue to administer it if it's no longer effective.

This is where the intuition of the Homburg research team comes to the fore. What may be of no use for one type of therapy (an ineffective drug) might turn out to be beneficial in another form of cancer therapy. 'We suspected, and later on we showed quite definitively, that the density of PSMA sites on the surface of the tumour cell increases when the adrogen receptor to which testosterone attaches is blocked,' says Ezzidin. The gut feeling within the research group, combined with the group's clinical observations, strongly suggested that this mechanism would still function in patients for whom the receptor-blocking drug (enzalutamide) was no longer itself therapeutically effective and was therefore no longer being prescribed.

The intuition of the medical research team proved to be spot on. 'We were able to prove that administering enzalutamide resulted in a significant increase in the PSMA density on the tumour surface, even though the drug was no longer effective in its original therapeutic sense and was no longer being prescribed for that purpose,' explains Samer Ezzidin. Despite the fact that only ten patients were involved the study, Professor Ezzidin believes that the results are compelling. 'After administering enzalutamide, we observed a significant increase in PSMA density on the tumour surface in all patients in the study. This allows us to introduce far more of the radioactive therapeutic agent into the tumour cells and thus irradiate them from the inside with irradiation paths that are down at the micrometre level,' says Ezzidin. As a result, PSMA radioligand therapy will be able to treat prostate tumours more efficiently and more selectively than has been possible in the past (see the following report for more details: https://www.eurekalert.org/pub_releases/2019-11/su-pcr112519.php).

'These findings now need to be subjected to further study and corroborated in a future research project,' explains Professor Ezzidin. 'But we wanted to publish our results as quickly as possible, as our findings may be of help to lots of patients. That's why we decided to first issue this short communication. I expect that even this small-scale study will lead to a drastic change in the therapy management regimens used when treating patients with advanced prostate cancer,' says Samer Ezzidin. And it's very likely that Professor Ezzidin's intuition will once again turn out to be right on the mark.

One of the last obstacles hindering the photography and filming of processes occurring on a scale of attoseconds, i.e. billionths of a billionth of a second, has disappeared. The key to its removal lies in the random nature of the processes responsible for the formation of X-ray laser pulses.

There are only a few X-ray lasers in the world today. These sophisticated devices can be used to record even extremely fast processes such as the changes in the electron states of atoms. The pulses generated by modern X-ray lasers are already short enough to be able to consider taking attophotos or even attofilms. However, what remained a problem was the X-ray optics itself. When an ultra-short X-ray pulse leaves the laser in which it was created, it can be extended in time over a dozen-fold. An international group of physicists under the supervision of Dr. Jakub Szlachetko and Dr. Joanna Czapla-Masztafiak from the Institute of Nuclear Physics of the Polish Academy of Sciences (IFJ PAN) in Cracow and Dr. Yves Kayser of the Physikalisch-Technische Bundesanstalt in Berlin has proved in Nature Communications that X-ray optics should no longer be an obstacle. The publication is the result of research conducted at the Linac Coherent Light Source (LCLS) X-ray laser at the SLAC National Accelerator Laboratory in Menlo Park, California.

"The best way to get rid of problems with X-ray optics was... to get rid of X-ray optics", laughs Dr. Szlachetko. "Instead of solving the problem, we found a way around it. It is interesting that we replaced the optics... by chance. Literally! We have shown that much better parameters than the current X-ray laser pulses can be obtained by skilful use of processes of a stochastic nature."

It is not the first case in the history of X-ray lasers when physics itself comes to the aid of designers. In classical lasers, the key element is the optical resonator. This is a system of mirrors that only strengthens photons of a certain wavelength, moving in a certain direction. X-ray lasers were for a long time considered impossible to construct due to the lack of mirrors capable of reflecting X-rays. This obstacle was eliminated when it was noticed that the resonator could be replaced... with relativistic physics alone. When an electron accelerated to velocity close to the velocity of light passes along a system of many alternately oriented magnets, it does not move in a straight line, but moves around it, losing energy at the same time. Relativistic effects then force the electron to emit high-energy photons not in any random direction, but along the original course of the beam of electrons (hence the name: Free-Electron Laser - FEL).

The high hopes associated with X-ray lasers are due to the fact that they can be used to record chemical reactions. Each single laser pulse can provide information about the current electron state of the system being observed (atom or molecule). At the same time, the pulse energy is so high that immediately after recording the image, the illuminated objects cease to exist. Fortunately, the observation process can be repeated many times. The images collected during a longer session enable scientists to accurately reconstruct all the stages of the studied chemical reaction.

"The situation can be compared to attempts to photograph events of the same type with a flash camera. When we take enough photos of a sufficient number of the same events, we can use them to construct a film with high accuracy showing what happens during a single event", explains Dr. Czapla-Masztafiak and explains: "The problem is that the pulses generated in X-ray lasers arise in spontaneous self-reinforcing stimulated emission and cannot be fully controlled".

The spontaneous nature of the pulses means that in X-ray lasers the parameters of subsequent pulses are not exactly the same. The pulses appear once earlier, once later, they also differ slightly in the energy of photons and their number. In the presented analogy, this would correspond to a situation when subsequent photos are taken with different flash units, in addition, activated at random moments.

The inevitable randomness of X-ray pulses forced physicists to mount additional optical diagnostic equipment in FEL lasers. As a result, even if the laser generated an original pulse of attosecond duration, it was extended by X-ray optics to femtoseconds. Now it turns out that to record the electronic states of atoms or molecules in a manner that allows for reconstruction of chemical reactions, impulses with precisely controlled parameters are not needed.

"Removing X-ray optics also allowed us to use of extremely high-energy pulses to study non-linear effects. This means that atoms begin to be transparent to X-rays at some point, which in turn is associated with an increase in absorption in a different range of radiation", explains Dr. Szlachetko.

The new method will be introduced in cooperation with IFJ PAN in experiments carried out using both current X-ray lasers: European XFEL near Hamburg (Germany) and SwissFEL in Villigen (Switzerland). The work related to testing the new technique in the context of chemical experiments was carried out in close cooperation with Dr. Jacinto Sa from the Institute of Physical Chemistry of the Polish Academy of Sciences in Warsaw and the University of Uppsala.

In the context of the proposed technique, it is worth emphasizing that in the case of classical optics there are some purely physical limitations related to the resolution of the optical instruments, for example the famous diffraction limit. There are no physical limitations in the new method - because there is no optics. So, if X-ray lasers appear with even shorter pulses than those currently generated, the new technique can be successfully used in them.

Parrots are considered extraordinarily clever animals. Alex, the famous Harvard-based African grey parrot, communicated with a vocabulary of more than 500 human words, could answer questions and classify objects spontaneously. Scientists from the Max-Planck-Institute for Ornithology based at the research station outpost for parrot comparative cognition in the Loro Parque in Tenerife, Spain, have shown that parrots exhibit a high level of social intelligence and cooperativeness. They readily help others, even when there is no immediate opportunity for reciprocation. Moreover, they reciprocate received favours and do not appear jealous, if conspecifics obtain a better reward than themselves. This further supports that they have evolved a level of intelligence comparable to that of great apes, crows and dolphins.

In the laboratory in the Max-Planck-outpost research station for comparative cognition run in collaboration with the Loro Parque Fundación, in Puerto de la Cruz, Tenerife, the African grey parrot Bella obtains a few metal tokens from a human experimenter. She has learnt to exchange those tokens with one of the scientist against her favorite food. But there is a problem - the exchange hole in her testing chamber through which the exchange occurs has been blocked.

In the neighboring test chamber there is her friend Kimmi waiting. Her exchange hole for the token exchange is open. However, Bella notices that Kimmi is lacking any tokens. What is he going to do?

Indeed, the parrot female picks up token after token and passes them over to Kimmi though an opening in the wall separating the two neighbouring chambers. The latter, seemingly pleased, accepts those gifts and readily exchanges them against treats. Bella in the meantime, rather relaxed, observes how Kimmi benefits from her generosity, without knowing that at a later point in time, the other may return the favor.

Helping partners

According to the most recent scientific findings, other than humans, only some great apes species behave similarly selfless towards unrelated individuals in comparable studies. In contrast, all other species tested so far in did not seem to pay attention to the wellbeing of conspecifics. They either behaved indifferently or even selfishly in comparable test situations. „Our parrots indeed seem to have grasped that another individual requires their help in order to achieve a goal", says Désirée Brucks, first author of the study. If Kimmi's exchange hole was blocked too however, Bella did not bother to pass over tokens. The African grey parrots therefore appear to recognize exactly when a conspecific actually benefits from their help and when it would not.

In a second study, the same parrots proved their general "prosocial attitude", i.e. their willingness to help and capacity to attend to the wellbeing of others. Besides, they showed the ability to reciprocate the other's previous actions, following a "tit-for-tat" strategy, which is seen as an important prerequisite for the evolution of cooperation. In the experiment, the birds had to decide between two types of tokens. One of them rewarded just the subject, whereas the other token provided food to both the subject and its neighbor. "Initially the parrots chose randomly, without paying any attention to the wellbeing of their neighbor", explains Anastasia Krasheninnikova, first author of this study. „As soon as the parrots were tested alternatingly with their neighbor, they very rapidly learned to choose the token that benefitted both birds."

No jealousy if others get better treatments

Further more, the research team has shown in a third recent study that parrots apparently are not jealous if a conspecific receives a better payoff for the same work performance than themselves, or has to work less hard for the same payoff. „At first, this finding came as a surprise, given that a „sense of fairness" is considered a prerequisite for the evolution of cooperation", says Auguste von Bayern, the leader of the comparative cognition research group. If you are able to detect when somebody is cheating upon you, you can react and switch to a fairer and thus better cooperation partner.

Whereas the parrots remained easygoing, primates, for example, do not put up with such an unequal treatment but show clear signs of anger and at some point boycott the unfair game. Possibly, the explanation for this is that parrots tend to be life-long monogamous, i.e. they remain pair-bonded with a single partner throughout their lives, whereas primates typically maintain affiliative relationships and/or coalitions with several partners in parallel and switch partners often as new opportunities arise. „Given that parrots are so closely bonded with a single individual and thus so mutually interdependent, it does not make any difference if one of them gets a better pay-off once in a while. What counts is that together, they function as a unit that can achieve much more than each of them on their own (in addition to raising their joint offspring). This is probably why parrots are much more tolerant towards unequal treatment than species that are not long-term monogamous, while still being excellent cooperators", explains Auguste von Bayern.

Scientists at Martin Luther University Halle-Wittenberg (MLU) and Georg August University Göttingen have succeeded in proving that a claw disease in cows is primarily genetic. Until now, the occurrence of interdigital hyperplasia has mostly been attributed to poor hygiene conditions in the barn. However, a team led by Professor Hermann Swalve discovered a farm in which the disease occurred frequently and was able to identify the gene responsible. As a result, the disease may now be contained through selective breeding.

"We rarely see such a case where everything fits perfectly together," says Hermann Swalve, Professor of Animal Breeding at the Institute for Agricultural and Nutritional Sciences at MLU. Many factors have to fit in order to find a single gene that is primarily responsible for a disease. Swalve's team, whose findings have now been published in the journal Frontiers in Genetics, succeeded in making the discovery because his research group had been working for years with large cow databases in Germany. In the course of their work, they came across a farm in which interdigital hyperplasia, also known as limax or tyloma, frequently occurred. Three to eight percent of all cows in Germany suffer from the disease at some stage in their lives, however it mostly affects older cows. A further, "stunted" claw emerges between the two claws of the hoof, spreading apart the real claws. "This results in tears to the skin, which in turn provide openings for bacteria and other infectious agents," says Swalve. The animals become lame and their lifespans are shortened.

"We previously carried out studies on the genetics of the disease, but we didn't have enough affected animals at our disposal, so it was difficult to obtain statistical certainty," explains Swalve. It was therefore a stroke of luck to find a farm in north-western Germany where almost 60 per cent of the animals were affected by it. In a genome-wide association study, they compared 45,000 small DNA segments, so-called SNPs, from healthy and sick cows. Initially, they identified two sites that could be related to the disease. One was the gene for tyrosine kinase receptor 2 (ROR2). "Next we compared our results with medical studies on humans and found that this gene also plays a role in the development of human limbs," says Swalve. The team from the University of Göttingen, led by Professor Bertram Brenig, subsequently provided proof that the ROR2 gene actually is involved with the development of the disease. His research group sequenced the entire gene segment and found that a mutation leads to the exchange of an amino acid in the affected cows. In further experiments, Brenig was also able to prove that the defect actually leads to an alteration in protein concentration. "Once we were able to show that the mutation influences gene expression, we were able to conclusively explain how it is connected to the disease," said Brenig.

Swalve is surprised that the genetic background of the disease had been ignored for so long - even though, as early as 1952, Richard Götze, an internationally acclaimed veterinarian from Hanover, suspected that interdigital hyperplasia was almost exclusively genetic. This discovery did not find its way into animal breeding. Only now, with this new study, has Götze's assumption been confirmed. The disease can now be tackled through selective breeding.

Researchers at Radboud university medical center have developed a 'deep learning' system that is better than most pathologists at determining the aggressiveness of prostate cancer. The AI system, which uses tissue samples to arrive at its diagnosis, taught itself to identify prostate cancer based on data from over 1200 patients. The Radboud team is now working with researchers from the Karolinska Institute in Sweden and Kaggle, a Google subsidiary, with the intention to continue developing these methods as part of a major international competition.

Prostate cancer is a frequently occurring type of cancer, but not always aggressive: more men die with prostate cancer than from prostate cancer. However, its treatment has many consequences for the quality of life of patients, so determining aggressiveness is an important step in choosing a treatment. To determine the aggressiveness of the cancer, pieces of tissue (biopsies) are taken from the prostate, which are scored by a pathologist. This 'Gleason score' is then used to classify biopsies into five groups - the Gleason Grade Groups - which indicate the risk of dying from prostate cancer. However, this is a subjective process; whether and how a patient is treated may depend on the pathologist who assesses the tissue.

Better than a pathologist

The researchers at Radboudumc developed an AI system that examines those biopsies the same way a pathologist does. The AI system also determines the Gleason score, and then the system can classify a biopt according to the Gleason Grade Groups. By means of deep learning, the system examined thousands of images of biopsies to learn what a healthy prostate is, and what more or less aggressive prostate cancer tissue looks like. Researcher Wouter Bulten describes this process: "The AI system has now been trained with 5759 biopsies from more than 1200 patients. When we compared the performance of the algorithm with that of 15 pathologists from various countries and with differing levels of experience, our system performed better than ten of them and was comparable to highly experienced pathologists." An additional advantage of such a computer system is that it is consistent and can be used anywhere; the treatment of a patient no longer depends on the pathologist looking at the tissue.

An international competition

As 1.2 million men globally are diagnosed with prostate cancer every year, the development of an AI diagnostic system is interesting for many research groups and companies. "It is advantageous that we are an academic hospital," says Bulten. "We are close to the patient and the practitioner, and have our own database of biopsies." As a next step, the Radboud university medical center team - together with researchers from the Karolinska Institute in Sweden and Kaggle, a subsidiary of Google specialized in data science competitions - wants to hold an international competition in which participants try to beat the Radboudumc algorithm. The insights resulting from this competition will then be used to improve the algorithms.

Background: what is 'deep learning'?

Deep learning is a term used for systems that learn in a way that is similar to how our brain works. It consists of networks of electronic 'neurons', each of which learns to recognize one aspect of the desired image. Then it follows the principles of learning by doing, and practice makes perfect. The system is fed more and more images that include relevant information saying - in this case - whether this is cancer or not, and if so, what the Gleason score is. The system then learns to recognize which characteristics belong to cancer, and the more pictures it sees, the better it can recognize those characteristics in undiagnosed images. (We do something similar with small children: we hold up an apple in front of them and say that it is an apple. At a certain point, you don't have to say it anymore.) A major advantage of these systems is also that they learn much faster than humans and can work 24 hours a day.

The Nijmegen study, authored by Wouter Bulten, Geert Litjens and others, has been published in The Lancet Oncology.

Cardiff University scientists have shed new light on the Earth's climate behaviour during the last known period of global warming over 14 million years ago.

During this period, known as the middle Miocene Climate Optimum, global temperatures were as much as 3 to 4 degrees warmer than today's average temperatures, similar to estimates for 2100. The position of the continents were similar to today and the seas were flourishing with life.

This period, which occurred between 15 and 17 million years ago, has puzzled geologists for decades as they have tried to explain the initial cause of the global warming and the environmental conditions that existed on Earth afterwards.

It is already known that this period of global warming was accompanied by massive volcanic eruptions which covered most of the modern-day Pacific Northwest in the USA, called the Columbia River flood basalts.

Around the same time a significant oil-rich layer of rock, known as the Monterey Formation, was created along the coastline of California as a result of the burial of carbon-rich marine life.

Up until now scientists have struggled to piece together the puzzle and come up with a viable explanation for the origin of the warmth and the link between the volcanic eruptions and the increased amounts of carbon burial.

Prof Carrie Lear, the senior scientist on the study and based at Cardiff University's School of Earth and Ocean Sciences, said: "Our planet has been warm before. We can use ancient fossils to help understand how the climate system works during these times."

In their study, published today in the journal Nature Communications, the team used the chemistry of marine fossils taken from long sediment cores from the Pacific, Atlantic and Indian oceans to fingerprint the temperature and carbon levels of the seawater in which the ancient creatures once lived during the middle Miocene Climate Optimum.

Their results showed that the massive volcanic eruptions of the Columbia River flood basalts released CO2 into the atmosphere and triggered a decline in ocean pH. With global temperatures rising as a consequence of this, sea-levels also rose, flooding large areas of the continents.

This created the ideal conditions to bury large amounts of carbon from the accumulations of marine organisms in sediments, and to transfer volcanic carbon from the atmosphere to the ocean over tens of thousands of years.

"The elevated marine productivity and carbon burial helped to remove some of the carbon dioxide from the volcanoes and acted as a negative feedback, mitigating some, but not all, of the climatic effects associated with the outpouring of volcanic CO2," said lead author of the study Dr Sindia Sosdian from Cardiff University's School of Earth and Ocean Sciences.

Past large episodes of volcanism throughout Earth's history have been linked to mass extinctions and widespread oxygen depletion in the oceans; however, there was no such occurrence in the middle Miocene Climate Optimum.

Co-author of the study Dr Tali Babila from the School of Ocean and Earth Sciences at the Univesity of Southampton added: "During the Miocene Climatic Optimum the response of the oceans and climate was remarkably similar to other massive volcanic eruptions in the geological record. The presence of the Antarctic ice sheet and the relatively slow release of carbon however minimised the magnitude of environmental change and the associated consequences on marine life during this event."

"Thanks to our findings we now have a very clear picture of what was going on over 14 million years ago and this will change the way that scientists look at this period of global warming," continued Dr Sosdian.

"We know that our current climate is warming much faster than the Miocene Climatic Optimum so we won't be able to rely on these slow natural feedbacks to counteract global warming. But this research is still important because it helps us understand how our planet works when it is in a warm mode."

As many as seven to 10 million people in the world are thought to live with Parkinson's disease (PD). Being the second most common neurodegenerative disease, PD severely affects patients' quality of life, not just brining movement abnormalities. Despite its prevalence and negative impact, current medical treatments for PD rely on alleviating PD symptoms with little efforts to explore ways to reverse the symptoms.

It has been firmly believed that abnormal movements of PD begin in the brain where the production of dopamine, a neurotransmitter for movement control, is irreversibly impaired, i.e. in a state of neuronal death. Currently, L-DOPA, a potent PD medication is mainly prescribed to replenish dopamine in the deprived brain. However, such a treatment is symptomatic therapy, rather than a disease-modifying therapy. Long-term use of L-DOPA is well-known to cause serious side effects such as involuntary, erratic, and writhing movements.

Led by Dr. C. Justin Lee along with Dr. Hoon Ryu and Dr. Sang Ryong Jeon, researchers at the Center for Cognition and Sociality within the Institute for Basic Science (IBS), Korea Institute of Science and Technology (KIST), and Asan Medical Center (AMC) have discovered a new mechanism for PD pathology. The researchers reported that the symptoms of PD begin when dopaminergic neurons are "non-functional", even before they die off. Though the neuronal death had been till now believed to be the obvious cause of PD, the study found that the movement abnormalities of PD begin in the earlier stage when dopaminergic neurons, though being alive, cannot synthesize dopamine (in a dormant state). "Everyone has been so trapped in the conventional idea of the neuronal death as the single cause of PD. That hampers efforts to investigate roles of other neuronal activities, such as surrounding astrocytes," said Dr. C. Justin Lee, the corresponding author of the study. Lee adds, "The neuronal death ruled out any possibility to reverse PD. Since dormant neurons can be awakened to resume their production capability, this finding will allow us to give PD patients hopes to live a new life without PD."

The researchers observed when the number of astrocytes abnormally increases due to the destruction of nearby neurons, GABA, an inhibitory neurotransmitter is released in the brains of both animal PD models and human patients in an excessive amount. This excessive output of GABA suppresses dopaminergic neurons, putting the production of dopamine on a hold. Notably, they confirmed that the dormant dopaminergic neurons are alive with the existence of DOPA decarboxylase. Furthermore, they revealed that these neurons could be awakened by treatment with MAO-B inhibitor, which blocks astrocytic GABA synthesis. The awakening of dormant dopaminergic neurons leads to a significant alleviation of PD motor symptoms.

They also used optogenetic tools to inhibit dopaminergic neuron of normal rats, inducing Parkinsonian motor deficits. They also demonstrated that activating the dormant dopaminergic neurons by the optogenetic treatment can alleviate PD motor symptoms. "This research refutes the common belief that there is no disease-modifying treatment for PD due to its basis on neuronal cell death," said Dr. Hoon Ryu of Brain Science Institute at KIST. "The significance of this study lies in its potential as the new form of treatment for patients in early stages of PD."

Dr. Sang Ryong Jeon of AMC explained, "So far, it had been firmly believed that idiopathic PD is caused by the death of dopaminergic neurons in substantia nigra. However, this research demonstrates that functional inhibition of dopaminergic neurons by surrounding astrocytes is the core cause of PD. It should be a drastic turning point in understanding and treating PD and possibly other neurodegenerative disease as well." With this study, the researchers suggest that disinhibiting dormant dopaminergic neurons by blocking excessive astrocytic GABA could be an effective therapeutic strategy against PD, especially in early stages of PD in which non-functional yet live dopaminergic neurons are waiting to be awaken.