Culture

When water is scarce, plants can close their pores to prevent losing too much water. This allows them to survive even longer periods of drought, but with the majority of pores closed, carbon dioxide uptake is also limited, which impairs photosynthetic performance and thus plant growth and yield.

Plant accomplish a balancing act - navigating between drying out and starving in dry conditions - through an elaborate network of sensors. An international team of plant scientists led by Rainer Hedrich, a biophysicist from Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany, has now pinpointed these sensors. The results have been published in the journal Nature Plants.

Microvalves control photosynthesis and water supply

When light is abundant, plants open the pores in their leaves to take in carbon dioxide (CO2) which they subsequently convert to carbohydrates in a process called photosynthesis. At the same time, a hundred times more water escapes through the microvalves than carbon dioxide flows in.

This is not a problem when there is enough water available, but when soils are parched in the middle of summer, the plant needs to switch to eco-mode to save water. Then plants will only open their pores to perform photosynthesis for as long as necessary to barely survive. Opening and closing the pores is accomplished through specialised guard cells that surround each pore in pairs. The units comprised of pores and guard cells are called stomata.

Guard cells have sensors for CO2 and ABA

The guard cells must be able to measure the photosynthesis and the water supply to respond appropriately to changing environmental conditions. For this purpose, they have a receptor to measure the CO2 concentration inside the leaf. When the CO2 value rises sharply, this is a sign that the photosynthesis is not running ideally. Then the pores are closed to prevent unnecessary evaporation. Once the CO2 concentration has fallen again, the pores reopen.

The water supply is measured through a hormone. When water is scarce, plants produce abscisic acid (ABA), a key stress hormone, and set their CO2 control cycle to water saving mode. This is accomplished through guard cells which are fitted with ABA receptors. When the hormone concentration in the leaf increases, the pores close.

Analysing the CO2-ABA network

The JMU research team wanted to shed light on the components of the guard cell control cycles. For this purpose, they exposed Arabidopsis species to elevated levels of CO2 or ABA. They did so over several hours to trigger reactions at the level of the genes. Afterwards, the stomata were isolated from the leaves to analyse the respective gene expression profiles of the guard cells using bioinformatics techniques. For this task, the team took Tobias Müller and Marcus Dietrich on board, two bioinformatics experts at the University of Würzburg.

The two experts found out that the gene expression patterns differed significantly at high CO2 or ABA concentrations. Moreover, they noticed that excessive CO2 also caused the expression of some ABA genes to change. These findings led the researchers to take a closer look at the ABA signalling pathway. They were particularly interested in the ABA receptors of the PYR/PYL family (pyrabactin receptor and pyrabactin-like). Arabidopsis has 14 of these receptors, six of them in the guard cells.

ABA receptors under the microscope

"Why does a guard cell need as many as six receptors for a single hormone? To answer this question, we teamed up with Professor Pedro Luis Rodriguez from the University of Madrid, who is an expert in ABA receptors," says Hedrich. Rodriguez's team generated Arabidopsis mutants in which they could study the ABA receptors individually.

"This enabled us to assign each of the six ABA receptors a task in the network and identify the individual receptors which are responsible for the ABA- and CO2-induced closing of the stomata," Peter Ache, a colleague of Hedrich's, explains.

Guard cells use ABA as currency in calculations

"We conclude from the findings that the guard cells offset the current photosynthetic carbon fixation performance with the status of the water balance using ABA as the currency," Hedrich explains. "When the water supply is good, our results indicate that the ABA receptors evaluate the basic hormonal balance as quasi 'stress-free' and keep the stomata open for CO2 supply. When water is scarce, the drought stress receptors recognise the elevated ABA level and make the guard cells close the stomata to prevent the plant from drying out."

Next, the JMU researchers aim to study the special characteristics of the ABA and CO2 relevant receptors as well as their signalling pathways and components.

Researchers from the Molecular Cancer group at the Hospital del Mar Medical Research Institute (IMIM) and doctors from Hospital del Mar, have demonstrated the effectiveness of a drug for treating metastatic bladder cancer in patients who did not respond to the usual treatment. The preliminary results of an ongoing clinical trial show that TAK-228, a mTORC1/2 protein inhibitor, can stop the progression of the disease. Four of the seven patients in the trial showed positive results. The trial also involved Hospital de la Santa Creu i Sant Pau in Barcelona, Hospital Universitari Parc Taulí in Sabadell, Clínica Universitaria in Navarre, and Hospital General Universitario in Elche.

The principle behind this drug (developed by the Japanese pharmaceutical Takeda), is the inhibition of the mTORC1/2 protein, commonly present in tumours. This protein plays a key role in the development and spread of tumours. The researchers analysed its effectiveness in the laboratory, in bladder cancer cell lines both in vitro and implanted into mice. They also worked with fresh tissue from the tumours of patients. The novelty is that, at the same time, they designed a clinical trial that is now underway.

The results, published in Molecular Cancer Research, demonstrate not only the good preclinical results of this drug, but that these are even better when combined with other treatments. At the same time, the researchers determined that it was more effective on a subgroup of tumours with particular characteristics, certain genetic alterations that could be used as therapeutic targets. "The fact of discovering a new mechanism of action for this mTORC1/2 inhibitor, beyond inhibiting this pathway, in other words, which acts against a molecular target -a specific genetic alteration, allows us to hope for much more than we originally expected", explains Dr. Joaquim Bellmunt, director of the IMIM and principal author of the study.

Good results in patients

The clinical trial, which evaluated seven patients, reports that four of these showed a positive response to the drug. In these sufferers, tumour growth was slowed and tumour progression avoided. These were metastatic bladder cancer patients who did not respond to the usual treatments, including immunotherapy. "For the moment," says Dr. Bellmunt, "we have obtained a metastatic bladder cancer response in patients in whom the existing therapies have not worked."

Currently in the United States, only one treatment for a bladder cancer molecular target has been approved. It is a unique treatment, differing from chemotherapy or radiation therapy. Dr. Bellmunt highlights this fact, pointing out that "the drug we have studied could become a second potential therapeutic target in bladder cancer patients. It is not chemotherapy, radiotherapy, or immunotherapy, but it attacks specific genetic alterations found in tumours".

Bladder cancer

It is the tenth most common cancer in the world, with 550,000 new cases in 2018 (according to World Cancer Research Fund). 65% of cases occur in developed countries, it is more frequent in men than women, and it is strongly linked to smoking (from 70-75% of cases).

It is typically detected between the ages of 65 and 70, although it can also be diagnosed at other ages.

The Spanish Society of Medical Oncology (SEOM) predicts that this year nearly 24,000 cases of bladder cancer will be diagnosed in Spain. According to data from this society, it is the fourth most common cancer in men and the fifth most common in women, and has a prevalence of almost 60,000 people. Although 5-year survival is high, 75% in men and 70% in women, by 2017 this type of tumour had caused 4,620 deaths in Spain. In Catalonia, 2,535 cases were diagnosed in 2017, 6.5% of the total of cancer cases in Catalonia, and 821 patients died of it.

Messenger RNA molecules contain genetic information and thus control the synthesis of proteins in living cells. Biochemists at the University of Bayreuth and the University of Bonn have now discovered a way to regulate this process which is central to gene expression: Certain actinobacteria contain a protein that binds RNA molecules under blue light and can thereby deactivate them. In principle, it is thus possible to switch RNA-controlled protein synthesis on and off via light, not just in bacteria but also in mammalian and even human cells. The findings published in "Nature Chemical Biology" are the basis for a new field of research: optoribogenetics.

For some time now, light signals have been used to alter the transcription of genetic information - and consequently protein synthesis directed by RNA (Ribonucleic Acids) molecules - at the DNA level. This approach is part of optogenetics and is now a well-established method of molecular and cell biology. However, the new study now shows for the first time a mechanism by which the interaction between RNA and specific proteins can be influenced by light. Gene expression in bacteria can hence be controlled directly at the level of RNA molecules.

The researchers led by Prof. Dr. Andreas Möglich in Bayreuth and Prof. Dr. Günter Mayer in Bonn have demonstrated that this mechanism can be transferred to mammalian cells. "Over the next few years, we will extend the light-controlled regulation to various cellular processes involving RNA. The resulting tools, which have not been available to date, will greatly advance the investigation of central cellular processes. The foundation stone for optoribogenetics, a new complement to optogenetics, has now been laid," says Prof. Dr. Andreas Möglich.

Search for a candidate protein reacting to light

The starting point of the research work was the hunt for a bacterial photoreceptor protein able to change its own binding behaviour in relation to RNA under the influence of light. The scientists searched the existing sequence databases and found what they were looking for. Bacteria of the species Nakamurella multipartita contain a protein with a conspicuous tripartite architecture: three different sections or "domains" called "PAS", "ANTAR" and "LOV", are arranged one after the other in an unusual sequence.

As could be shown in cooperation with the research group of Prof. Dr. Robert Bittl at Freie Universität Berlin, the LOV photosensor domain reacts to blue light and transmits the signals to the ANTAR domain. The ANTAR domain then changes its structure so that RNA molecules are bound and thus made inaccessible: They are no longer available for gene expression and the genetic information contained in them is no longer used for the synthesis of proteins.

Only when the blue light irradiation ceases, and the ANTAR domain returns to its normal structure, does the interaction with the RNA come to a halt. Now the RNA becomes active again. The researchers first established and demonstrated this process using RNA aptamers. These are small RNA molecules with a hairpin-like structure that can enter the structure of the ANTAR domain, which is opened under blue light, and are bound there. Mayer: "Aptamers work in modular fashion: They can be linked to other units like a building block system."

The scientists also tested their new research approach on eukaryotic cells into which they had previously introduced the bacterial protein and the RNA aptamers. In these cells, too, the structural changes triggered by blue light lead to messenger RNA molecules binding to the protein and, in this state, suspending gene expression. "We now have a light switch with which the cellular activity of different RNA molecules can be specifically switched on and off," explains Prof. Dr. Günter Mayer from the LIMES Institute at the University of Bonn.

His colleague from Bayreuth, Prof. Dr. Andreas Möglich, adds: "The approach to light-regulated control can in principle be transferred to numerous other RNA-based processes, such as the processing of micro-RNAs and the associated phenomenon of gene silencing." In subsequent studies, the two scientists and their research groups hope to investigate the extent to which the newly discovered mechanism can be used in model organisms to control gene expression and other processes.

With the celebration of the 50th anniversary of the moon landing this year, it could be argued that the greatest science of the 20th Century was about big machines that could travel the universe. The rise of nanotechnology is suggesting that the 21th Century will be dedicated to much smaller machines that can travel inside the smallest spaces including human cells. Researchers at Nara Institute of Science and Technology (NAIST), Japan, in partnership with research teams in the University Paul Sabatier (France) and Prof. Saw-Wai Hla in Ohio University (USA), report in Nature Communications the latest nanomachine, a propeller that can rotate at will in both clockwise and counterclockwise directions and transfer this motion to another molecule like gears.

Nature has proven exceptional at designing similar machines by using molecules that can convert optical, chemical or electrical energy into interactions with the surface to generate motion. "For many nanomachines, we look at nature as our model. There are many examples of propellers with which organisms move in dynamic environments. Surprisingly, these natural nanomachines take the shape of large-scale propellers," says NAIST Professor Gwénaël Rapenne, who contributed to the new study.

Consistently, the propeller designed by Rapenne and his colleagues consists of three components: three blades each composed of an indazole, a stator consisting of five phenyl groups, and a ruthenium atom that binds to the two and allow the rotation like a ball bearing.

One of the major differences is the conditions in which artificial nanopropellers work. Where natural nanomachines tend to work in environments comfortable for life, artificial nanomachines can work in much harsher conditions. Rapenne demonstrates this point by attaching his machine to a gold surface and observing that some begin swirling at extremely cold temperatures (near -200 oC). At the same time no propellers move at -275 oC, verifying their ability to convert thermal energy into movement.

The propellers also showed the capacity to rotate in different directions in a controlled manner, but never to switch directions. This was the result of how the propeller was attached to the gold surface, which caused a slight tilt in the stator. The direction of the tilt determined the direction of the spin. This feature is reminiscent to macroscopic propellers we see in the real world.

"The stator acts as a ratchet-shaped gear that imposes a unidirectional rotation," notes Rapenne.

This is not the first time Rapenne has used gold to prove the capabilities of his nanomachines. Two years ago, he and colleagues organized the world's first nanocar competition using gold tracks. While he does not expect to follow that effort with the first nano single propeller competition, he does believe the new machines will serve an important purpose in the nanoworld.

"Our propellers can displace nearby molecules, showing that they can be used to move molecular loads for faster transfer of energy or information," he says.

Today's physicists mostly focus either on massive objects like black holes or on atom-sized objects. In both cases, significant deviations from conventional laws of physics are observed. The understanding of atomic level processes opens a wide range of prospects in nanoelectronics and material engineering. One of such studies is a model suggested by a team of scientists from Peter the Great St.Petersburg Polytechnic University (SPbPU). The model describes the distribution of heat in ultrapure crystals at the atomic level. The article was published in was published in the Journal of Applied Mathematics and Mechanics.

The distribution of heat in nanostructures is not regulated by the laws applied to conventional materials. This effect is most vividly expressed in the reaction between graphene and a laser-generated heat point source. Graphene is a 2D crystal made of carbon atoms. The material looks like a thin grid or a honeycomb. However, it is quite stable and has very high heat and electrical conductivity due to which it is widely used in electrical engineering. The discoverers of this unique crystal were awarded the Nobel Prize in Physics in 2010.

Scientists of SPbPU considered an infinite crystal consisting of identical particles obeying classical Newtonian equations of motion. Graphene-based technologies are rarely used in vacuum, so the team also took into account the effect of the environment (gas or liquid). This adjustment has a considerable impact on the model as a part of heat is spent on warming up the environment. Finally, the team derived an analytical solution describing heat transfer. To describe the processes that happen in the material, the scientists obtained simple equations and confirmed them with numerical data generated in the model for different distances from the heat source. Using the developed model, the team observed that a crystal have certain directions along which the heat rays distribute the major part of energy. Currently the authors are preparing for an experiment to confirm their theoretical conclusions with actual heat processes in a graphene crystal.

"Our results may be widely used for investigation of heat transfer in micro- and nanoprocessors. It is of great importance for the development of new generation high performance computers. Our analytical approach can be applied to a wide range of ultrapure materials such as graphene", concluded Anton KRIVTSOV, corresponding member of the Russian Academy of Sciences, the Head of the Higher School "Theoretical Mechanics", Director of Research & Education Center "Gaspromneft-Polytech" at Peter the Great St. Petersburg Polytechnic University.

Exercise seems to endow a wealth of benefits, from the release of happiness-inducing hormones to higher physical fitness. New research shows it may provide a boost to the mind too.

University of Iowa researchers have found that a single bout of exercise improves cognitive functions and working memory in some older people. In experiments that included physical activity, brain scans, and working memory tests, the researchers also found that participants experienced the same cognitive benefits and improved memory from a single exercise session as they did from longer, regular exercise.

"One implication of this study is you could think of the benefits day by day," says Michelle Voss, assistant professor in the Department of Psychological and Brain Sciences and the study's corresponding author. "In terms of behavioral change and cognitive benefits from physical activity, you can say, 'I'm just going to be active today. I'll get a benefit.' So, you don't need to think of it like you're going to train for a marathon to get some sort of optimal peak of performance. You just could work at it day by day to gain those benefits."

Previous research has shown exercise can confer a mental boost. But the benefits vary: One person may improve cognitively and have improved memory, while another person may show little to no gain.

Limited research has been done on how a single bout of physical activity may affect cognition and working memory specifically in older populations, despite evidence that some brain functions slip as people age.

Voss wanted to tease out how a single session of exercise may affect older individuals. Her team enrolled 34 adults between 60 and 80 years of age who were healthy but not regularly active. Each participant rode a stationary bike on two separate occasions--with light and then more strenuous resistance when pedaling--for 20 minutes. Before and after each exercise session, each participant underwent a brain scan and completed a memory test.

In the brain scan, the researchers examined bursts of activity in regions known to be involved in the collection and sharing of memories. In the working memory tests, each participant used a computer screen to look at a set of eight young adult faces that rotated every three seconds--flashcard style--and had to decide when a face seen two "cards" previously matched the one they were currently viewing.

After a single exercise session, the researchers found in some individuals increased connectivity between the medial temporal (which surrounds the brain's memory center, the hippocampus) and the parietal cortex and prefrontal cortex, two regions involved in cognition and memory. Those same individuals also performed better on the memory tests. Other individuals showed little to no gain.

The boost in cognition and memory from a single exercise session lasted only a short while for those who showed gains, the researchers found.

"The benefits can be there a lot more quickly than people think," Voss says. "The hope is that a lot of people will then keep it up because those benefits to the brain are temporary. Understanding exactly how long the benefits last after a single session, and why some benefit more than others, are exciting directions for future research."

The participants also engaged in regular exercise, pedaling on a stationary bike for 50 minutes three times a week for three months. One group engaged in moderate-intensity pedaling, while another group had a mostly lighter workout in which the bike pedals moved for them.

Most individuals in the moderate and lighter-intensity groups showed mental benefits, judging by the brain scans and working memory tests given at the beginning and at the end of the three-month exercise period. But the brain gains were no greater than the improvements from when they had exercised a single time.

"The result that a single session of aerobic exercise mimics the effects of 12 weeks of training on performance has important implications both practically and theoretically," the authors write.

The researchers note their study had a small participant pool, with a homogenous population that excluded anyone with chronic health conditions or who were taking beta-blockers.

To address those limitations, Voss has expanded her participant pool in a current, five-year study to confirm the initial findings and learn more about how exercise alters older people's brains. The participants are healthy older individuals who are not physically active, similar to the participants' profile in the study's results reported here.

LAWRENCE -- Organizations inescapably categorize people, and those in the most desirable categories may do whatever it takes to stay there and to exclude others until a more desirable category emerges. However, dominant groups also can rerank existing favorable and unfavorable categories when weaker groups gain greater access to the traditionally favorable categories. Two University of Kansas professors have published a study of this reranking process in education, which they refer to as categorical manipulation.

The paper outlines a theory of the reranking process against the backdrop of research on status competition and organizational stratification. It then tests the theory by drawing on data from a large urban school district, where categorical manipulation occurred to keep racial minorities out of the most desirable mild disability categories.

The article's co-authors are Argun Saatcioglu, associate professor of educational leadership & policy studies and by courtesy sociology, and Thomas Skrtic, Williamson Family Distinguished Professor of Special Education. The study appears in the American Journal of Sociology.

When groups who have enjoyed status and prestige for a long time are forced to accept outsiders into their customary categories, they can move down to what formerly was a less prime slot and use their influence to redefine the terms of categorization. The practice has happened in business, employment and popular culture. For the article, the KU authors document how one city school district moved upper-class white students from the least stigmatizing and well-resourced disability categories into what, at the time, was the least desirable category when a court order forced desegregation in the 1970s and minority students started joining the top categories.

"The idea is that the categories are arranged like a ladder. The most desirable are at the top, and women and minorities only move up a rung if men and whites move up first," Skrtic said. "This also happens by people moving down, because there was pressure from below and that category now becomes the 'good' category because the so-called 'good people' are now in it."

Through the analysis of student and school records, and fiscal data, along with interviews with parents and district personnel, Saatcioglu and Skrtic document how the manipulation happened. In the early '70s, there were three categories of learning disabilities, denoted as LD, in the district: Those served in regular classrooms, those pulled out for services in resource rooms and those placed full-time in segregated LD classrooms, which the authors refer to as LD1, LD2 and LD3, respectively. LD1 was most desirable, as it received the most support from teaching aides, the most exposure to the regular curriculum and least segregation from general education classrooms. LD1 students were typically white and from middle- and upper-class backgrounds. The district was slow to integrate following the Brown v. Topeka Board of Education decision, and a court order in the '70s required more integration. As more black students from low socioeconomic backgrounds began moving into LD1, white students who were there moved to LD3. Saatcioglu and Skrtic document how what was formerly the least desirable category, LD3, became the new destination.

"When desegregation started, they moved the white LD1 kids into LD3," Skrtic said. "We showed that not only did they do that, but they moved the kids and moved the money with them. But low-income white kids stayed behind. It was a racist as well as a classist move."

What was the least desirable category, LD3, was redefined by additional financial support, more support from teachers' aides and more support in testing and other measures. The shift was achieved by manipulating testing practices to artificially deflate the official performance of students formerly in LD1 and any incoming white student who normally would have been categorized as LD1. Soon after being labeled as LD3, white students' achievement went up, as the full curriculum and supports went with them to a category that now had more desirable conditions. White parents, including those interviewed for the study, created what was called the Learning Disabilities Association, which helped coordinate the moves. As white, middle- and upper-class parents moved into the district, the association informed them of the best placements, their changes and the attached benefits for their children.

"It wasn't like black students were going to dominate LD1 -- not that there would be anything wrong with that -- but the mere threat that at least some black kids were now coming into LD1 created significant concern among white parents, who started leaving like crazy... some left the district altogether," Saatcioglu said. "We've seen such exit behavior in traditionally white neighborhoods once a few black families move in. The difference here is that instead of moving out to other all-white neighborhoods, white families had to refurbish a previously all-black category and then keep blacks out of there."

The study was funded by a grant from the Division of Social and Economic Sciences of the National Science Foundation. The authors point out that by further studying categorical manipulation, researchers can understand how even fully complying with demands for change can fail to result in genuine change as dominant groups redefine status. They implore scholars to look for the phenomenon in other areas as better understanding how it happens can help prevent the perpetuation of inequality. In their own ongoing work, Saatcioglu and Skrtic are examining federal data from 1998 to 2006 to further understand how educational labels are parsed out through racial and class means, and how middle- and upper-class white parents have been able to hoard the best categories.

"This paper is about organizations and inequality," Saatcioglu said. "Our study documents how categorical manipulation occurs in schools, but it can happen in any bureaucratic context where people are labeled."

Bacteria could be used to produce large quantities of medicines and fuels using a new gene programming technique, research suggests.

The powerful method could enable bacteria to be used as cheap and environmentally friendly living factories that make a range of useful products.

It will allow researchers to target genes that are normally difficult to activate, including those involved in infections, or with industrial applications.

The advance could also make it easier to study how harmful strains of bacteria thrive and cause infections, researchers say.

Scientists at the University of Edinburgh invented the new technique - known as programmable gene activation - which enables them to control a wider range of genes and increase product yields.

Until now, a lack of techniques that work well in bacteria has hindered research and limited their ability to be used to make useful products.

Using the new method, levels of gene activation are around 100 times higher than existing techniques, the team says. Current methods also mainly target basic genes involved in bacterial survival.

The team's technique is adapted from an approach that uses scissor-like molecules - called CRISPR molecules - to make precise changes to the genetic code. They adapted the technology by attaching small guide molecules and proteins that target and switch on genes.

Their technique was developed for a widely studied species called Escherichia coli and a soil bacterium with potential industry applications. The method is also likely to work in many other species of bacteria, researchers say.

The team also developed a reusable scanning platform that makes it faster and cheaper to find the best ways of activating multiple genes in a pattern that produces high yields of useful substances.

The study, published in the journal Nature Communications, was funded by the Biotechnology and Biological Sciences Research Council, UK Research and Innovation, Leverhulme Trust and Wellcome.

Dr Baojun Wang, of the University of Edinburgh's School of Biological Sciences, who led the study, said: "This new method has the potential to be a powerful tool for programing bacteria, with diverse applications for research and industry. It could help save a lot of time and money."

Thanks to the advent of super-resolution microscopes some 30 years ago, scientists can observe subcellular structures, proteins and living tissue with unprecedented precision. These microscopes operate by measuring the fluorescent light that some compounds emit naturally or the light emitted by artificial fluorophores, and by exploiting various quantum properties of the fluorophore, can deliver a resolution smaller than the one imposed by the diffraction limit. One problem is that image quality varies considerably with the particular instrument being used and its settings - such as how powerful the laser is and how the individual components are aligned - as well as with the proprieties of the sample being studied.

A team of scientists at EPFL's Laboratory of Nanoscale Biology, headed by Aleksandra Radenovic in the School of Engineering, has developed an algorithm that can estimate a microscope's resolution in just a few seconds based on a single image. The algorithm's result indicates how closely a microscope is operating to its full potential. This could be particularly useful for the automated microscopes that have started appearing in research labs. The team's findings have just been published in Nature Methods.

A single image

The scientists used Fourier's transform as the basis for their algorithm, but they modified it so as to extract as much information as possible from a single image.

The results indicates how closely a microscope is operating to its full potential © EPFL

The algorithm performs the calculation in just a few seconds and generates a single number. "Researchers can compare this number with the microscope's maximum possible resolution to see whether the instrument can work even better or modify the experimental conditions and observe how the resolution evolves" says Adrien Descloux, the study's lead author.

The algorithm can be used with any kind of imaging modality, including super-resolution models. "Our technique is particularly promising for the emerging generation of automated microscopes, where a computer adjusts all their settings," says Radenovic. Her lab's algorithm is the first ever to allow researchers to estimate a microscope's resolution from a single image. Previously two images were needed, and the results were subject to high uncertainty if the images were not correctly pre-processed.

So that their discovery can be used on a large scale, the algorithm has been made available as an open source Image plugin. Researchers can download the tool and directly obtain the algorithm estimate - showing them how closely their microscope is operating to its maximum resolution. "Our algorithm is universal. And because only one image is needed, it is particularly suited for fast optimization of imaging conditions, which is challenging when observing dynamic processes. Also, the method can be applied in the image processing, as feedback for optimization of the advanced image reconstruction algorithms," concludes Descloux.

The study investigated epileptic seizures in zebrafish - a widely used model organism for modelling human brain physiology. Zebrafish contains the same cell types that are present also in human brains. Two of these cell types are glia and neurons. Neurons are primarily involved in transmitting signals. The main functions of Glial cells include maintaining a balanced environment and providing support for the neurons, assisting the immune system and increasing the speed of neural signalling.

The study found that just before an epileptic seizure, nerve cells were abnormally active but only in a localized area of the brain. Instead, glial cells showed large burst of synchronous activity that are widely dispersed across the brain. During the actual seizure, the neuronal activity increased abruptly. The functional connections between the nerve cells and glial cells became vigorous. When this happened, generalized seizure spread like a storm of electrical activity across the entire brain due to a strong increase in the level of glutamate, a chemical compound that transmits signals between neuronal cells. Glutamate was secreted by glial cells, which convert themselves from a friend to a foe.

The findings indicate that epilepsy may occur not only due to anomalies in neurons, but also in glial cells. "Our results provide a direct evidence that the interactions between glial cells and neurons change during the transition from a pre-seizure state to a generalized seizure. It will be interesting to see if this phenomenon is generalizable across different types of epilepsies," says Prof. Emre Yaksi. Normally, the glial cells absorb the excess glutamate that is excreted during the increased activity of the nerve cells. This study assumes that the secretion process of the glial cells that we observed in combination with their hyperactivity just before a seizure is a defence mechanism of the brain.

The shipping industry is vital to the existence of the global trade economy, yet seafarers face one of the highest risks of workplace injury or death. Understanding the causes and reducing the frequency of occupational injuries not only benefits the seafarers but directly benefits the shipping companies by reducing premiums, liabilities and legal costs. A new article published in Risk Analysis: An International Journal investigates the causes of these injuries and accidents and finds that injury reduction campaigns focused on personal protective equipment (PPE) would be most effective at reducing risks to workers.

The study, "Quantitative risk assessment of seafarers' nonfatal injuries due to occupational accidents based on Bayesian Network modeling," was conducted by a team of Singapore -based researchers. The team conducted an extensive survey to collect data on seafarers' working practice and their injury records.

A survey was designed to test the following potential risk factors: sex, age, experience, nationality, ship type, position, time in position, tour duration, change of ship, familiarity, training, adequate rest, distraction, job risk awareness, job risk assessment, risk communication, procedure design, shortcut, housekeeping, defective equipment/tools, PPE availability, PPE training, PPE usage, reasons not using PPE, shore visit frequency, maintenance, accident feedback loop and injury during latest tour. The researchers collected 354 responses from seafarers in Singapore, China, South Korea and Vietnam. These countries were selected because of their high representation in the international seafaring market.

The survey results indicated that:

Fourteen percent of seafarers suffered at least one injury during their latest tour of duty.

The biggest influential risk factors were age, risk awareness, sea experience and PPE availability.

Four percent reported not having received proper PPE training, yet the injury rate among those respondents was as much as 33 percent higher.

PPE availability was shown to have the greatest potential to decrease injury probability.

The 'risk awareness' factor could be improved through training and 'accident feedback loop,' but 18 percent of respondents reported that their company did not always share the accident lessons with the crew.

Since PPE availability is the most significant factor, it is suggested that:

Management could focus on improving the supply and stock of proper, nondefective PPEs aboard their vessels.

For companies looking to implement a new safety campaign, periodic review of the need for PPE for each task and subsequent updates of the PPE type, size and quality could be introduced.

Companies need to ensure that all workers are receiving training on the proper use of PPE as that is as important as the supply of equipment itself.

The risk awareness of employees could be improved by frequent sharing of common injuries, communicating risk assessment results and posting warning signs at the sites of potential hazards.

In situations where PPE was readily available, seafarers identified that the equipment's 'impact on efficiency' was the top factor that could hinder the use of PPE, followed by unavailable, uncomfortable and don't feel necessary. Management could improve upon these factors during the selection of PPEs and aim to develop a workplace culture that promotes PPE usage at all times.

"Shipping is the lifeblood of world trade and its viability depends on the key workforce - seafarers, who are competent and have their occupational health and safety assured at work. This research reveals key findings related to factors that have been shown to have the greatest potential to decrease injury probability of seafarers - the key element in the eco-system that contributes to IMO's goal of 'Safe, secure and efficient shipping on clean oceans,'" states Vinh Thai, associate professor at RMIT University, Australia.

New Rochelle, NY, August 26, 2019--Cannabis can help alleviate some of the symptoms of cancer and its treatment, and a new study examines the prevalence of its use among young adult cancer patients now that medical cannabis is becoming increasingly available. The demographic and clinical factors likely to correlate with cannabis use and differences in moderate to severe symptoms between users and non-users are reported in a study published in Journal of Adolescent and Young Adult Oncology (JAYAO), a multidisciplinary peer-reviewed publication from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article free on the Journal of Adolescent and Young Adult Oncology (JAYAO) website through September 26, 2019.

Kristine Donovan, PhD, MBA and colleagues from Moffitt Cancer Center, Tampa, FL coauthored the article entitled "Cannabis Use in Young Adult Cancer Patients." On urine drug testing for a breakdown product of cannabis, they showed that 30% of young adult cancer patients ages 18 to 39 tested positive. The researchers report that this prevalence rate of cannabis use is higher than for young adults in the general population and adult cancer patients seeking specialized symptom management. Young adult cannabis users were more likely to be male and, surprisingly, to report having more severe symptoms, including pain, nausea, lack of appetite, constipation, and difficulty sleeping.

Editor-in-Chief of JAYAO Leonard S. Sender, MD, CHOC Children's Hospital Hyundai Cancer Institute, Orange, CA, states: "As cannabis becomes legal for medical and recreational use in more states, it is increasingly important that its use in cancer patients is evidence-based. More research is needed into premorbidity and effectiveness relative to other pharmacological agents."

Elderly women battling breast cancer who have anxiety, depression or other mental health conditions are more likely to use opioids and more likely to die, a new study led by the University of Virginia School of Medicine suggests.

The findings should encourage doctors to better manage mental health in patients with breast cancer and spur care providers to consider alternative pain management such as physical therapy, massage and acupuncture, the researchers say.

"The complex relationship among breast cancer, mental health problems, and the use of opioids is not well understood and the results of this study provide clinicians the evidence they need to make optimal patient treatment related decisions," said lead researcher Rajesh Balkrishnan, PhD, of the Department of Public Health Sciences and the UVA Cancer Center. "Our findings suggest that patients with breast cancer with mental health conditions have higher opioid use and reduced survival. These results highlight the need for health care providers to evaluate treatment goals and assess whether better concurrent management of breast cancer and mental health conditions is required."

Breast Cancer and Opioids

Breast cancer kills more than 40,000 people in the United States each year, and patients often suffer from anxiety and depression. Research suggests that about 40 percent of patients with breast cancer have some type of mental health diagnosis.

Balkrishnan and his team set out to shed light on the relationship among mental health, opioid use and breast cancer outcomes. To do that, they reviewed more than 10,000 breast cancer cases recorded in the national SEER cancer database, which contains detailed (but depersonalized) information on care provided to Medicare beneficiaries with cancer. These cases consisted of women aged 65 years and older who were diagnosed with stage I, II or III breast cancer between Jan. 1, 2006, and Dec. 31, 2012. All received adjuvant endocrine therapy as treatment.

The researchers sorted the cases into two groups: women with mental health diagnoses and those without. They found that those with mental health diagnoses had higher opioid use and lower survival rates.

"Opioid use is higher in the women with breast cancer who suffer from mental health comorbidities and remains a significant problem," the researchers write in a new paper outlining their findings. "In addition, mental health comorbidities also contribute to reduced survival in these women. A need exists for collaborative care in the management of mental health comorbidities in women with breast cancer, which could improve symptoms, adherence to treatment, and recovery from these mental conditions. Mental health treatments also are recommended to be offered in primary care, which not only would be convenient for patients but also would reduce the stigma associated with treatments for mental health comorbidities and improve the patient-provider relationship."

The researchers, including UVA palliative care expert Leslie Blackhall, MD, recommend that doctors and other care providers consider "complementary forms of treatment for pain," such as physical therapy, cognitive behavioral therapy, acupuncture, acupressure and massage.

Findings Published

The researchers have published their findings in the Journal of Oncology Practice. In addition to Balkrishnan and Blackhall, the study's authors were Raj Desai, of the University of Florida; Fabian Camacho of the UVA School of Medicine; Xi Tan of West Virginia University; and Virginia LeBaron, of the UVA School of Nursing.

The researchers noted potential limitations to their study such as a lack of information on the opioids used and a lack of details on the patients' pain assessments. They also suggest that mental health conditions such as depression may be underdiagnosed and that, as a result, the research may underestimate the percentage of patients with those conditions.

Tan disclosed potential conflicts of interest including owning stock in and receiving compensation from biopharmaceutical company Merck. Balkrishnan disclosed that he has done consulting or advising for Merck.

An international team of BHF-funded researchers may have discovered why some people experience muscle pain after taking statins. The research, published in JACC: Basic to Translational Science, could help doctors prevent a known side effect of statins and ensure people are able to reap the benefits of the life-saving drugs.

According to the research, statins cause spontaneous and irregular leaks of calcium from storage compartments within muscle cells. Under normal conditions, coordinated releases of calcium from these stores make the muscles contract. Unregulated calcium leaks may cause damage to muscle cells, potentially leading to muscle pain and weakness.

The researchers suggest that in most people, muscle cells can tolerate this calcium leak. However, in people already susceptible due to their genes or lifestyle, the leak caused by statins may overwhelm the muscle cells, giving rise to muscle pain and weakness.

The findings explain why only some people experience muscle pain after taking statins and could help doctors to identify those most likely to experience symptoms so they can be offered alternative therapies.

The researchers also showed that exercise may prevent the changes which lead to calcium leaks from occurring, and it may be an effective way for people taking statins to avoid muscle symptoms.

Statins reduce a person's risk of a heart attack or stroke by lowering the levels of so-called 'bad cholesterol' in the body. They are particularly beneficial for people who have already had a heart attack or stroke and are also effective in those who are identified as being at risk of having one in future. Although side effects are rare, muscle pain and weakness are important reasons why some people stop taking these potentially life-saving drugs.

Researchers based at the University of Leeds and the Karolinska Institute in Sweden investigated the effects of statins on muscle biopsies from patients taking statins long term and from rats treated with statins for 4 weeks.

Treatment with statins compromised gatekeeper proteins called ryanodine receptors, which control calcium release from storage compartments in muscle cells, leading to spontaneous and irregular calcium leaks that could trigger signals promoting cell death. Pro-cell death signals were elevated in muscles from both people and rats treated with statins compared to untreated controls.

Despite the cell changes, statins did not affect muscle function or strength in rats. These findings support the theory that muscle cells can tolerate the calcium leak, meaning only those who are susceptible experience symptoms.

Importantly, the study also suggests that the potentially harmful effects of statins on muscle can be countered with exercise. When rats were given free access to an exercise wheel, the statin-related changes to the gatekeeper proteins no longer occurred and pro-cell death signals were not elevated in the muscles. In fact, rats treated with statins ran twice as far as control rats. The findings challenge previous reports that exercise makes statin side effects worse.

The researchers point out that they did not directly show that the cell changes lead to muscle weakness and pain in people, but note that this is likely. The proposed mechanism may also explain why heart muscle, which has different gatekeeper proteins for calcium release, is protected from any potentially harmful effects of statins.

Dr Sarah Calaghan, Associate Professor in Cardiac Physiology from the University of Leeds said:

"The idea that exercise makes statin side effects worse might be a misconception - what really matters is the intensity of exercise. We found that moderate exercise cancelled out the changes in muscle cells caused by statins. We know around 7 in 10 professional athletes can't tolerate statins - and we know that intense endurance exercise has profound effects on the gatekeeper proteins targeted by statins. The added effect of statins could push muscles over the edge, leading to symptoms.

"The good news is, after twenty years of searching, we finally have an explanation for statin-associated muscle pain, along with a possible solution. If you weren't convinced to exercise already, here's another reason."

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation said:

"Statins are life-saving drugs and most people who take them don't experience side effects. Those who do suffer muscle pain and weakness should always ask their doctor if a different statin or dose might solve the problem.

"Identifying how statins affect muscle cell biology is the first step in preventing potential muscle side effects - and ensuring that people who are susceptible to those side effects do not miss out on the protection afforded by statins.

"Ultimately, everyone has control over the medications they choose to take. When weighing up whether to take statins, talk to your GP. After assessing your personal risk and advising on lifestyle changes, they will help you make an informed decision that is right for you."

A new species of gigantic tumbleweed once predicted to go extinct is not only here to stay -- it's likely to expand its territory.

The species, Salsola ryanii, is significantly larger than either of its parent plants, which can grow up to 6 feet tall. A new study from UC Riverside supports the theory that the new tumbleweed grows more vigorously because it is a hybrid with doubled pairs of its parents' chromosomes.

Findings from the study are detailed in a new paper published in the Oxford University-produced journal AoB Plants.

"Salsola ryanii is a nasty species replacing other nasty species of tumbleweed in the U.S.," said study co-author Norman Ellstrand, UCR Distinguished Professor of Genetics. "It's healthier than earlier versions, and now we know why."

Humans are diploid organisms, with one set of chromosomes donated by the mother and one set from the father. Sometimes a mother's egg contains two sets of chromosomes rather than just the one she is meant to pass on. If this egg is fertilized, the offspring would be triploid, with three sets of chromosomes. Most humans do not survive this.

Plants with parents closely related enough to mate can produce triploid offspring that survive but are unable to reproduce themselves. However, a hybrid plant that manages to get two copies from the mother and two from the father will be fertile. Some species can have more than four sets of chromosomes. They can even have "hexaploidy," with six sets of chromosomes.

Scientists have long assumed there must be some kind of evolutionary advantage to polyploidy, the term for hybrids that have multiple sets of chromosomes, since it poses some immediate difficulties for the new hybrids.

"Typically, when something is new, and it's the only one of its kind, that's a disadvantage. There's nobody exactly like you to mate with," said study co-author Shana Welles, the graduate student in Ellstrand's laboratory that conducted the study as part of her Ph.D. research. She is now a postdoctoral fellow at Chapman University.

The advantage to having multiple sets of chromosomes, according to the study, is that the hybrid plant grows more vigorously than either of its parents. This has been suggested as the reason polyploidy is so common in plants. However, it has not, until now, been demonstrated experimentally.

Polyploidy is associated with our favorite crops; domesticated peanuts have four sets of chromosomes, and the wheat we eat has six.

Though tumbleweeds are often seen as symbols of America's old West, they are also invasive plants that cause traffic accidents, damage agricultural operations, and cause millions in property damage every year. Last year, the desert town of Victorville, California, was buried in them, piling up to the second story of some homes.

Currently, Salsola ryanii has a relatively small but expanding geographic range. Since the new study determined it is even more vigorous than its progenitors, which are invasive in 48 states, Welles said it is likely to continue to expand its range. Additionally, Welles said climate change could increase its territory takeover.

Though this tumbleweed is an annual, it tends to grow on the later side of winter.

"It's one of the only things that's still green in late summer," Welles said. "They may be well positioned to take advantage of summer rains if climate changes make those more prevalent."

Given its potential for damage, the knowledge now available about Salsola ryanii could be important for helping to suppress it, and Ellstrand believes that is what should happen before it takes over.

"An ounce of prevention is a pound of cure," he said.