Tech

The Texas Heart Institute (THI) has announced that a research team led by Dr. Mehdi Razavi, Director of Electrophysiology Clinical Research & Innovations, has developed a breakthrough new ex vivo benchtop system for evaluating the effects of ablation systems on excised tissues and assessing potential damage to collateral heart tissues. The unique system allows for fast and easy benchtop assessments rather than using costly in vivo tests. Critical findings associated with this innovation are outlined in a study published in the Journal Cardiovascular of Electrophysiology.

The new ablation method evaluated by Dr. Razavi and team is being assessed and used clinically as a promising development to combat the challenge of reducing atrial esophageal fistulas - which are uncommon but often deadly late-stage complications of atrial fibrillation ablation procedures that result from massive thermal injury to the esophagus and surrounding components. Atrial fibrillation (AF) is the most common sustained heart rhythm disorder in clinical cardiology practice worldwide.

"We created this custom, simple, easy to use fixture to study different ablation settings and the collateral impact of the ablation on the surrounding tissues. It has been useful not only in this particular study, but in many of our other projects as well. It's quite versatile," said Mathews John, Dr. Razavi's Research Engineer III at THI." Our expertise in ablation and access to an extensive set of ablation equipment enabled us to do these experiments in a way that truly mimics what actually happens in a clinical setting."

The most critical finding of the study is that High Power Short Duration (HPSD) ablation protocols may be associated with greater epiesophageal thermal deviations relative to endoluminal measurements. The inaccuracy, in turn, raises the threat of downstream clinical consequences. The results of this ex vivo study support the need for esophageal temperature monitoring, particularly during HPSD ablation.

"Electrophysiology doctors have been utilizing this method previously, but no one has really taken a closer look at the full scope of thermodynamics in play during ablation operations," Dr. Mehdi Razavi noted. He added, "Current technology does not monitor temperature outside of the esophagus during the procedure; it can only monitor temperature changes inside the esophagus itself, which is significant given the fact that major temperature changes occur outside of the organ. To that end, our study sheds light on the problem related to the lack of ability to comprehensively track temperature during these types of procedures and presents an ex vivo method for mitigating this setback."

The study setup detailed in the manuscript was easily modifiable for collaborations with outside companies to evaluate their new devices in order to help them better gather thermodynamic data and validate potential users of the novel technology.

"Overall, our publication demonstrates very interesting findings from the comparison of two different commonly used ablation methods that have been evaluated using this benchtop system and highlights safety measures that should be considered in a clinical setting. The THI Electrophysiology Clinical Research & Innovations team is excited to use this system for further evaluation and characterization of novel cutting-edge ablation systems," Dr. Razavi concluded.

The Texas Heart Institute research presented in the Journal of Cardiovascular Physiology represents a preliminary study of these differences; further studies with larger sample sizes and within vivo characterization will be required to make clinical recommendations.

Neurons are the primary cells of the nervous system, and the signals that are transmitted between them are responsible for all our actions and our cognitive ability. In particular, learning and memory are believed to be associated with a process called "long-term potentiation," which is the strengthening of connections between specific neurons via continued signal transmission through "synapses" (small gaps between neurons). Long-term potentiation can change the connection between neurons via synapses--by changing their size and composition. Understanding how long-term potentiation occurs can be valuable to clarifying how our brain learns and retains new knowledge. A team of scientists from Japan has now made significant strides in the understanding of long-term potentiation. Read on to know how!

One way to study long-term potentiation is by using "optogenetics," i.e., activating neurons and monitoring their responses upon light stimulation. Optogenetics allows scientists to activate single neurons and dissect how neurons work in neuronal networks. As such, optogenetics is a revolutionary advancement in neuroscience research, but optogenetic tools to modify single synapses (spines) have not been developed until now. This is an issue because neuronal signaling pathways may have spine-specific effects. In particular, the protein "CaMKII," critical for long-term potentiation, is activated by the molecule "glutamate" in a spine-specific way, but exactly what happens at the synapses during activation remains a mystery.

Fortunately, a research team at National Institute of Physiological Sciences, Japan, led by Dr. Hideji Murakoshi, resolved this issue. The team fused CaMKII with a specific domain of a plant photoreceptor (a type of cell that responds to light). This domain called "LOV2-Jα" caused CaMKII to become sensitive to light, after which they expressed this new photoactivatable CaMKII in different types of isolated neurons and in living mice. Their findings are recently published in the journal Nature Communications.

"We were very excited to find that activating CaMKII triggers some important effects, specifically recruiting receptors that cause a chain reaction that then leads to long-term potentiation," Dr. Murakoshi explains. The process physically changes the dendritic spines, expanding them, an outcome that the scientists also observed in their experiments. Importantly, all that was needed for this process to happen was CaMKII activation--to put it in scientific terms, CaMKII activation was sufficient for long-term potentiation of individual dendritic spines, which had not been demonstrated before. The team also used light-based imaging technology and the light-activated CaMKII to determine what signaling molecules are activated during long-term potentiation. All of these findings combine to provide a better picture of how long-term potentiation occurs at the synapse level.

"In addition to the valuable information we uncovered about an important neurological process, our light-activated CaMKII is a major addition to existing optogenetic tools," Dr. Murakoshi comments when asked about the significance of their work. "We've created something that can be used to manipulate neuronal signaling and investigate synaptic plasticity--or the physiological changes that happen at individual synapses during events like memory formation."

The scientists are optimistic that with further development, the ability to manipulate synapses also has important implications for the treatment of brain diseases (such as autism)--a remarkable feat for neuroscience!

Rivers and lakes at high latitudes are considered to be major sources for greenhouse gas emissions to the atmosphere, but these losses are poorly constrained. In a study published in Nature Communications, Umeå University researchers and collaborators quantify carbon emissions from rivers and lakes across Western Siberia, finding that emission are high and exceed carbon export to the Arctic Ocean.

High latitude regions play a key role in the global carbon cycle and climate system. An important question is the degree of mobilization and atmospheric release of vast soil carbon stocks, partly stored in permafrost, with amplified warming of these regions. A fraction of this carbon is exported to inland waters and emitted to the atmosphere, yet these losses are poorly constrained and seldom accounted for in assessments of high latitude carbon balances. This is particularly relevant for Western Siberia, with its extensive peatland carbon stocks that are expected to be affected by climate warming.

Now researchers at the Climate Impacts Research Centre (CIRC), Umeå University, and collaborators from Russia and France have quantified the carbon emission from inland waters of Western Siberia. Due to the remoteness and large area (3.6 million km2 area) of the study region, sampling of lakes and rivers were carried out over several years.

"We collected data of representative lakes and rivers over 2,000 km distance, including the main channel of Arctic's largest watershed the Ob' River", explains lead author Jan Karlsson.

Based on these data and information on the distribution of inland waters of the region the research team show high carbon emission from Western Siberian inland waters and that these systems play an important role in the continental carbon cycle.

"Our results emphasize the important role of carbon emissions from inland waters in the regional carbon cycle. The carbon emission from the inland waters was almost an order of magnitude higher that carbon export to the Arctic Ocean and reached nearly half of the region's land carbon uptake."

The high significance of inland waters in the carbon cycle of Western Siberia is likely a result of the overall flat terrain, which lead to relatively high water coverage and long water transit times, and thus favorable conditions for decomposition and outgassing of land derived carbon in inland waters. The authors stress that further studies on the coupled land-water carbon cycle are needed in order to improve the understanding of regional differences in the contemporary carbon cycle and predictions of future conditions in these understudied and climate-sensitive areas.

"Ignoring carbon outgassing from inland waters will likely largely underestimate the impact of warming on these regions and overlook their weakening capacity to act as terrestrial carbon sinks."

Cryopreservation involves preserving biological materials, such as cells, tissues, and organs, at ultra-low temperatures so that they can be revived and used at a later date. To achieve cryopreservation such that the preserved materials are not damaged, scientists use various chemicals called cryoprotectants, which facilitate the freezing process. Unfortunately, many of the existing cryoprotective agents have major limitations. For example, dimethyl sulfoxide is useful for cryopreserving red blood cells, but it is also toxic to the cells.

To overcome these limitations, researchers at the Japan Advanced Institute of Science and Technology (JAIST) and Japan's RIKEN have experimented with a class of chemicals known as polyampholytes, identifying one polyampholyte named carboxylated ε-poly-?-lysine (COOH-PLL) as a promising cryoprotectant that does not have toxic effects on cells.

However, the mechanism by which COOH-PLL acts as a cryoprotectant remained poorly understood, and this hindered efforts at developing better polyampholyte cryoprotectants. To address this knowledge gap, this team of researchers, which was led by Professor Kazuaki Matsumura from JAIST--and which also included Asst. Prof. Robin Rajan from JAIST and Dr. Fumiaki Hayashi and Dr. Toshio Nagashima from RIKEN--conducted another study in which they used a method called solid-state nuclear magnetic resonance (NMR) spectroscopy to characterize what happens to water molecules, sodium and chloride ions, and a form of COOH-PLL called PLL-(0.65) when they are mixed and frozen to temperatures used in cryopreservation. Their findings appear in a recent issue of the peer-reviewed journal Communications Materials.

As expected, the NMR signals recorded from these frozen solutions indicated reduced molecular-level mobility and increased solution viscosity (i.e., increased resistance to flow) at ultra-low temperatures. Importantly, the PLL-(0.65) molecules trapped the water molecules and ions in ways that prevented the formation of intracellular ice crystals and countered the effects of osmotic shock (a form of physiological dysfunction in which a sudden change in ion concentrations around a cell can lead to rapid inflow or outflow of fluid into or from the cell, damaging it). Intracellular ice crystals and osmotic shock are major causes of cellular or tissue damage during freezing, so the ability of PLL-(0.65) to prevent both helps to explain its effectiveness as a cryoprotectant.

In describing the scientific value of these findings, Prof. Matsumura notes that the use of NMR "enabled the characterization of the cryoprotective properties of polymers that operate through mechanisms different from those of current cryoprotectants." He predicts that this characterization "will facilitate the molecular design of new cryoprotectants," which will "promote the clinical use of polymeric cryoprotective agents that can serve as efficient alternatives to small molecule agents such as dimethyl sulfoxide and glycerol."

Small molecule cryoprotectants are only useful for preserving cells and small tissues, but polymeric cryoprotectants may enable researchers to achieve the cryopreservation of larger tissue volumes or even whole organs. This would be an important advance for emerging fields such as regenerative medicine, which aims to restore normal physiological functions by replacing or regenerating cells, tissues, and organs.

The team's findings may also have important implications for basic biology. In recent years, scientists have learned that intrinsically disordered proteins, which lack a fixed three-dimensional shape, serve an important role in protecting cells from damage related to desiccation and osmotic shock at low temperatures. Because proteins are themselves a class of polyampholytes, these recently published findings concerning COOH-PLL's behavior at ultra-low temperatures may help to explain the mechanisms by which intrinsically disordered proteins protect cells. Further research into the mechanisms of such proteins may in turn lead to the development of advanced materials with uses in regenerative medicine.

In conclusion, these findings may be of considerable value to biology and medicine. "Based on our now-improved understanding of mechanisms of polymeric cryoprotective agents," notes Prof. Matsumura, "we expect to develop new cryopreservation technologies for large tissue volumes and organs, which will permit the industrial-scale implementation of regenerative medicine via the establishment of banks of engineered tissues." These steps towards regenerative medicine will do much to improve the lives of people living with medical disorders that are currently incurable.

Glaciers are not only melting, but also collapsing in the Third Pole region. In 2016, two glaciers in the western Third Pole's Aru Mountains collapsed, one after another. The first collapse caused nine human casualties and the loss of hundreds of livestock. However, that may not be the end of the catastrophe.

According to a study recently published in The Cryosphere, meltwater from ice avalanches has been filling downstream lakes in a way that may cause previously separated lakes to merge within the next decade, thus disrupting the function of ecosystems in the region.

"The collapse of Aru glaciers has both short-term and long-term impacts on downstream lakes," said Dr. LEI Yanbin, lead author of the study and a researcher at the Institute of Tibetan Plateau Research (ITP), Chinese Academy of Sciences.

According to LEI and his team, the first glacier collapse sent at least 7.1 million cubic meters of ice, the volume of approximately 2,840 Olympic-size swimming pools, into the downstream Aru Co Lake. The avalanche of ice lowered the lake's surface temperature by 2-4 degree centigrade for two weeks and reshaped the near-shore lakebed. As the ice from the avalanches started to melt, it contributed 23% to the volume increase of Memar Co Lake, a neighboring terminal lake that has risen three meters from 2016 to 2019 - a rate that is 30% faster than that from 2003 to 2014.

The study was enabled by the glacier-meteorology-lake observation system built by a group of scientists led by Prof. YAO Tandong, co-chair of Third Pole Environment (TPE) and co-author of the study.

YAO and his group were the first scientists to arrive at the scene after the glacier collapse, and have since been working to reveal why and how the glaciers collapsed, as well as trying to understand the impact of the collapses on downstream lakes.

Their research found that ice avalanche debris from the first glacier collapse had nearly melted away by the summer of 2017, but 30% of the ice from the second glacier collapse still remained as of the end of 2019. "If Memar Lake continues to expand at this rate, it will merge with the Aru Co Lake in 7-11 years," said YAO. "A scenario like that could significantly change the regional landscape and disrupt local ecosystems. That's why we need to watch the two lakes more closely in case of such changes."

The BioRescue research project, a programme aiming at saving the northern white rhinoceros from extinction, exemplifies the challenges to overcome when conducting research and conservation in an international consortium in times of a global pandemic. COVID-19 hampered communication and travels, prevented or delayed crucial procedures, caused losses in revenues and by that may have lowered the chances of a survival of the northern white rhino. The consortium adjusted strategies, gained valuable knowledge during these challenging times and continued with its mission. The effects of the pandemic on the BioRescue project are described in detail in a scientific paper published in the Journal of Applied Animal Ethics Research.

There are only two northern white rhino individuals left in the world, both females. To prevent the extinction of the northern white rhino, an international consortium of scientists and conservationists seeks to advance assisted reproduction technologies and stem-cell associated techniques to create northern white rhino embryos in-vitro. In the near future, the embryos will be transferred to southern white rhino surrogate mothers to create northern white rhino offspring. This boundary-pushing programme is conducted by an international team working within a global framework and includes scientists and conservationists from institutions in Germany, Kenya, Japan, Czech Republic, USA and Italy. From March 2020 onwards, the work of the consortium has been severely affected by the Covid-19 pandemic in several ways at the local, national and international level.

At the international level, the most striking obstacle were international travel restrictions. "The consortium partners had previously agreed upon collecting oocytes from the last two northern white rhinos every three to four months. This is considered a safe interval to maintain the health of the females while maximising the number of harvested oocytes, equivalent to potential future embryos and offspring" says BioRescue project head Thomas Hildebrandt from the Leibniz-Institute for Zoo and Wildlife Research (Leibniz-IZW). Following such an interval, oocyte collection was planned for March 2020 at the Ol Pejeta Conservancy in Kenya. "Owing to international travel restrictions, the procedure had to be cancelled and could only be conducted after the re-opening of Kenya's borders in August 2020," adds Leibniz-IZW BioRescue scientist Susanne Holtze, who shares first authorship of the publication with Hildebrandt. "This does not only mean that one crucial opportunity was missed and possibly several valuable embryos could not be generated, it also affected the subsequent procedure in August 2020," Holtze explains. It is likely that the prolonged interval since the last oocyte collection in December 2019 compromised oocyte quality and was the reason that out of 10 oocytes, no embryos could be created. The delay of possible embryo transfers in Kenya will also decrease chances for northern white rhino calves to grow up with individuals of their kind. This ultimately implies that almost a year was lost for the programme - a serious delay in the race against time to prevent the extinction of the northern white rhino. "On the other hand, the involuntary break provided us with valuable new insights into the reproduction management of northern white rhinos," says Hildebrandt. "We still made progress in 2020 as we could successfully continue our research with our Kenya mission in December."

In addition to the delays in conducting the procedures at Ol Pejeta Conservancy in Kenya, for which strict travel regulations and on-site hygiene rules had to be followed, the pandemic posed several further challenges to the consortium. Lockdown and temporal closures of public facilities caused notable losses in revenues for the consortium partner Safari Park Dv?r Králové in the Czech Republic. "We faced the unprecedented situation of having no revenues from entrance fees and other services. However, against all odds, we were quickly able to develop new ways of how to approach our potential visitors and supporters online and this allowed us to keep our support to the northern white rescue programme on the same level as in previous years. Our highest priority is protecting species from extinction and COVID-19 confirmed how important the support by individual donors is," says Jan Stejskal, the Safari Park's Director of Communication and International Projects. Similarly, the not-for-profit Ol Pejeta Conservancy experienced drastic reductions in revenue from international tourism owing to a ban on international travel, national curfews and the isolation of the capital Nairobi. "Therefore, fundraising was necessary to maintain our wildlife and conservation programmes and pay for salaries," says Ol Pejeta Managing Director, Richard Vigne. "Nevertheless, safeguarding the animals and professional veterinary care were maintained at all times in cooperation with the Kenya Wildlife Service."

For the research facilities of the consortium partners in Germany, Italy and Japan, different levels of restrictions were put in place on laboratory work. Crucial work at Leibniz-IZW, Avantea Laboratory of Reproductive Technologies (Italy), Kyushu University (Japan) and the Max Delbrück Center for Molecular Medicine (Germany) could be carried on to a limited extent. "Staff at labs was limited, hygiene rules were enacted, transportation of samples and equipment were hampered and last but not least closure of schools and child care facilities forced parents to switch from lab work to mobile work at home," Sebastian Diecke from Max Delbrück Center sums up. Laboratories and offices at the University of Padova were also closed and online-teaching and research was implemented. The team in charge of the ethical monitoring of the BioRescue programme continued working from home, and had to adjust strategies to carry on the ethical assessment for all procedures. "Despite all difficulties, the ethical assessment was always performed and BioRescue procedures have uninterruptedly maintained high standards of quality and respect for the safety and welfare of both researchers and the animals involved," says Barbara de Mori from University of Padua.

"COVID-19 has disastrous consequences all over the world, but two new embryos that we produced in December 2020 demonstrate that our BioRescue team is committed to overcome all scientific and logistic challenges the northern white rhino rescue might bring. We will be grateful for everyone who decides to support us in our mission," adds Jan Stejskal."

Besides the downside effects of the pandemic, there were also a few positive ones. For example, closure of international borders opened up new opportunities for assisted reproduction procedures in Germany which were important for advancing and perfecting methods and techniques. For example, a designated mating partner of a southern white rhino female in a German zoo could not be transferred and therefore, assisted reproduction was a welcome alternative to regular natural mating. Secondly, social distancing regulations helped to establish a new culture of online meetings within the consortium partners on a more regular basis, which proved useful and will continue in future. Lastly, there is a renewed awareness for the destruction of habitat and the loss of biodiversity as key drivers for emerging zoonotic diseases. "BioRescue is not only about saving the northern white rhino. On the long run it also is a much-needed step for the healing of disrupted habitat in Central Africa and therefor for preventing global pandemics in future," says Thomas Hildebrandt. "It is ironic and bitter, that our mission was severely affected by the very thing it ultimately intends to make more unlikely, a pandemic." More information about BioRescue as well as options how to support the project can be found on http://www.biorescue.org.

In the span of only 15 years, a small academic elite has increased its share of academic citations significantly. In the year 2000, 14 per cent of all citations went to the top one percent of the most cited researchers. New research shows that this figure had risen to 21 per cent in 2015.

The people behind these remarkable findings are senior researcher Jens Peter Andersen, Danish Centre for Studies in Research and Research Policy (CFA) at Aarhus BSS, Aarhus University, and associate professor Mathias Wullum Nielsen (former CFA, now University of Copenhagen). Their examination of almost 26 million scientific papers and four million authors has just been published in the well-established interdisciplinary journal Proceedings of the National Academy of Sciences (PNAS).

"We had expected an increase, but we are surprised to find such a large one, meaning that more than every fifth citation now goes to such a small elite. This development might cause worry because we risk that a small powerful elite acquires immense influence on research ideas; on what is even considered as research topics," says Jens Peter Andersen.

A monopoly on the marketplace of ideas?

You could ask whether healthy competition exists when one per cent of researchers receive such a large share of the citations? Jens Peter Andersen points out that the trend can lead to an increased 'monopoly on the marketplace of ideas'.

According to Jens Peter Andersen, increased international competition leads to an academic world marked by greater inequality and in which the most cited researchers attract a growing part of the attention.

"Our data show that there is an elite who increasingly sets the agenda for the production of knowledge," says Jens Peter Andersen and continues:

"When established researchers set the agenda, we risk a stagnation in breakthroughs. This is a problem of diversity, not only related to those who get the opportunity to do research but also to the scope of ideas and methods that are accommodated - ideas and methods that could develop research along new lines."

An accelerating trend

The data do not say anything about the cause of the increasing citation concentration.

"You could imagine a self-reinforcing circle in which numerous citations lead to more grants and a broader network as a researcher, triggering an even larger number of citations," says Jens Peter Andersen.

According to Jens Peter Andersen, this has unfortunate consequences for the majority of researchers, seeing as citations play a large role in the applications for research funds and employment.

"It is not a one-to-one correlation, but all things being equal, those who receive many citations will often receive more grants and have an easier time getting accepted by the right places," says Jens Peter Andersen and continues:

"This makes it more difficult for others."

Jens Peter Andersen does not expect the accelerating trend to stop here, but rather a further increase in grants, publications and citations among elite researchers.

"We are now seeing more huge teams and interdisciplinary collaborations, the fusion of research fields, big data as well as improved measurements and computational techniques, and these factors could all play a role in increased citation concentration. However, it will require additional research to establish this link," he concludes.

When human cells have to adapt due to a wide variety of external influences, the BAF complex plays a central role because it controls the accessibility of the DNA and thus the information stored in it. In every fifth human cancer, a mutation is found in one of the BAF complex genes. Scientists from the research group of Principal Investigator Stefan Kubicek at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences have investigated this complex in more detail using novel techniques and were able to show how quickly changes in the BAF complex genes influence the accessibility of DNA. The study has now been published in Nature Genetics.

Chromatin is a central component of the cell nucleus and refers to the material that makes up the chromosomes. It organizes the approximately two meters of human DNA in such a way that certain genes are activated or deactivated depending on the cell type. The smallest "packaging unit" of chromatin is the nucleosome, consisting of 146 base pairs of DNA wrapped around a histone octamer. Whenever cells need to adapt, for example due to environmental influences or developmental signals, corresponding changes to chromatin are necessary. These are carried out by various enzymes, including chromatin remodeling complexes, which use the energy of adenosine triphosphate (ATP) to move nucleosomes along the DNA or to remove them completely. One important chromatin remodeling complex is the BAF complex. It consists of up to 14 subunits encoded by 29 genes which interact in different combinations. Previous studies have found mutations in certain subunits of the BAF complex in numerous cancers. In their recently published study, CeMM Principal Investigator Stefan Kubicek and his research group investigated the direct effects of changes in the BAF complex on DNA accessibility.

Faster than the cell cycle

In order to observe the functions of chromatin remodeling complexes, commonly genetic methods are used which can inactivate these proteins within 3-5 days. However, due to the slowness of these technologies, they were hardly suited to determine the immediate effects of changes to the BAF complex on DNA accessibility. Therefore, the scientists Sandra Schick, Sarah Grosche and Katharina Eva Kohl from Kubicek's research group relied on a so-called degron system. "Here, too, we use CRISPR genome editing. But instead of destroying a BAF subunit, we fuse it with a small protein called a 'dTag'. By adding a specific active substance, we can then recruit the 'dTag'-tagged subunit to components of the cellular 'waste removal'. The labelled BAF subunit is then degraded within one hour. This makes it possible to precisely observe whether and how accessibilities subsequently change," explain the study authors. Stefan Kubicek adds: "Our study has shown that removing a specific subunit of the BAF complex immediately leads to a loss of accessibility to certain DNA regions. The effect appears immediate, hinting that the cell cycle plays no role in this process. We were also able to confirm these results with pharmacological inhibitors of the BAF complex, which showed particularly fast effects. We assume that processes similar to those in our model system also play a role in carcinogenesis when mutations of a subunit of the BAF complex occur in cells for the first time."

Synthetic lethality amplifies effect

In earlier studies, Kubicek's research group had already investigated how different genes within the BAF complex interact. This showed that cells in which only a certain BAF subgroup has a mutation and reduces DNA accessibility can continue to live and grow. In some cases, however, the additional deactivation of another, specific subgroup leads to cell death. This interaction of specific genes is called synthetic lethality. A known synthetic lethality exists in the two genes SMARCA2 and SMARCA4. Cells can tolerate the loss of either of these genes but die as soon as both are mutated. Mutations of SMARCA4 have been found to be particularly common in cancer cells. Specific SMARCA2 inhibition has the potential to exploit synthetic lethality to specifically kill these SMARCA4-mutated cancer cells without damaging healthy cells. In their current study, the study authors observed the immediate effects of synthetic lethality. "We wanted to know what happens when we remove both subunits," says study author Sandra Schick. This showed that compared to the loss of each individual subunit, even more regions of the DNA lose accessibility, especially those that are crucial for cell identity. "We see that so-called 'super-enhancers', very active gene regulatory regions, only lose their accessibility when we trigger this synthetic lethality, i.e. lose both SMARCA4 and SMARCA2."

BAF complex needs constant activity

In addition, the scientists tried to trigger the same effect using pharmacological substances. These inhibit the activity of the BAF complex and prevent it from moving nucleosomes. Project leader Stefan Kubicek explains: "Our results show that maintaining the accessibility of BAF-controlled sites in the genome requires constant ATP-dependent remodeling. This means that the BAF complex needs constant energy provided by ATP to move nucleosomes and thus maintain access to the DNA. Complete abrogation of the BAF complex function results in a near-total loss of chromatin accessibility at BAF-controlled sites."

"86 percent of the respondents rate the home office regulation as appropriate," says BfR-President Professor Dr. Dr. Andreas Hensel. "This illustrates that people also accept changes in their everyday occupational life in order to contain the coronavirus."

https://www.bfr.bund.de/cm/349/210119-bfr-corona-monitor-en.pdf

Day-care centres and schools are still closed except for emergency care. However, this measure is judged as appropriate by a decreasing number of respondents: Since the beginning of the year, approval has dropped by 10 percentage points from 67 percent to now 57 percent. A similar development can be seen in the acceptance of the closure of shops: In the current survey, about half of the respondents consider the measure to be appropriate. Shortly before Christmas, this figure was still at 66 percent.

The lockdown, which has been in place since November, is increasingly perceived as a burden. The number of people who are worried about their social relationships rose from 30 percent at the beginning of the year to 40 percent in the current poll and is thus higher than at any other time in the survey. In addition, the proportion of people who think the existing contact restrictions are appropriate fell to 69 percent, which is at a similarly low level as in the early summer of 2020.

However, concern about the effects of the coronavirus on the economic situation and physical health has remained fairly consistent at between 20 and 23 percent in recent weeks. In the current survey, a quarter say they are concerned about their own mental health. The age group of 14 to 39-year-olds is particularly affected: Here, just under half of the respondents are worried about their social relationships and a good third about their mental health. This is considerably less the case in the older age groups.

During the COVID-19 pandemic, small and medium-sized firms (SME) have become increasingly dependent on social media as a tool for their international sales process, according to a recent study published in International Business Review. Digital communication tools seem to be most prevalent in finding and reaching new prospects and in the persuasion phase, whereas more traditional communication tools still prevail in customer relationship management.

"During the COVID-19 outbreak, small and medium sized firms have become more reliant on social media tools to reach internationally dispersed prospects and customers. Such use has helped them to overcome limitations set to face-to-face interaction by the pandemic," lead author, Senior Researcher Sara Fraccastoro from the University of Eastern Finland says.

The study clarifies the benefits of integrating social media to other sales communication tools during the business-to-business sales process phases. However, there seem to be important potential boundary conditions, including relationship culture, location proximity, technology resources, and strategic importance of the customer that affect the way international SMEs use different communication tools during a sales process.

"Our research team has assumed a leading position in research dealing with how B2B firms apply social media in their international sales. Our findings provide a structured framework for managers on how to best integrate social media into their communication portfolio along the sales process phases for international markets," Professor Mika Gabrielsson from the University of Eastern Finland says.

In both life and music, the secret to success is love. This universal emotion stands out as the key protagonist in the most listened-to songs of all time. According to a study by Salvador Climent Roca and Marta Coll-Florit from the GRIAL applied linguistics research group (tied to the UOC Faculty of Arts and Humanities), love is central to 52 of the 71 songs that topped the Billboard magazine's year-end charts from 1946 to 2016. "Pop music is created to achieve commercial success, and evocations of feelings of love and unrequited love are powerfully attractive for all types of audiences," said the authors.

Their analysis, published in open access in the Text and Talk journal, explores an area little explored by academics: pop music. "Few studies have qualitatively analysed the discourse reflected in the lyrics of hit songs. This kind of analysis helps us study social trends on a large scale," explained Climent Roca. The study analysed the lyrics of the songs most listened to in the USA over seven decades to explore how conceptions of love have changed over time.

The study indicates that metaphors represent over 70% of the figurative language used to express feelings of romantic love in pop music. "This observation corresponds to theoretical predictions that indicate that much of our thinking relies on metaphorical language, as metaphor helps us to effectively express concepts and complex emotions," said Coll-Florit. By analysing the metaphors used most often, we can see how love and associated feelings and experiences have been conceptualized over the years.

Metaphors for talking about love

Starting with the smoochy "Prisoner of Love" by Perry Como and ending with the viral hit "Love Yourself" by Justin Bieber, the journey through the most popular love songs of each era also reveals that the way we talk about love has changed in recent history. According to the analysis by Climent Roca and Coll-Florit, each of the songs analysed uses metaphor to speak of love. Among the hundreds of love metaphors used most, those that refer to love as proximity, possession, union, physical contact, captivity or as a journey stand out. It is also common to speak of the loved one as 'baby' or in terms of appetizing food.

Three quarters of the most popular songs about love refer to romantic love, while the rest have erotic themes. Put in perspective, the analysis reflects a curious phenomenon. From the 1970s, US pop music has used more sensual and explicit metaphors to talk about love. The analysis shows that songs with erotic themes are concentrated between 1977 and 1982, featuring in the six songs most listened to each year. Another boom in explicitly sensual songs occurs between 1996 and 2008, with five such hit songs in those 13 years. The analysis also reveals that 14 of the 15 songs listened to most between 1983 and 2016 refer to the anguish of love.

From physical proximity to possession

Many of the songs refer to love in terms of physical proximity: from the desire to be near the loved one to the contact of fusion between lovers. Many other songs speak of love in terms of possession or captivity. At least a score of the most popular love songs depict an unequal love relationship, in which one of the lovers considers the other to belong to them. In several cases, love is reflected as yet another form of subjugation. Just over two thirds of the songs, in fact, reflect a correlation between metaphors of physical proximity and of possession; in other words, both ideas seem to overlap.

"It's normal that physical proximity metaphors, as emerging naturally from love relationships, would be used in love songs. Metaphors of possession, on the other hand, reflect a cliché deeply rooted in popular culture," said Climent Roca and Coll-Florit. Their "All you need is love" study invites us to look beyond the catchy melodies and gain a deeper understanding of lyrics that we have all joined in with at one time or another, singing our hearts out in accompaniment.

Rising global temperatures are causing frozen Arctic soil-- permafrost--in the northern hemisphere to thaw and release CO2 that has been stored within it for thousands of years. The amount of carbon stored in permafrost is estimated to be four times greater than the combined amount of CO2 emitted by modern humans.

Research results from an international team, which includes a researcher from the University of Copenhagen among others, suggests that the newly discovered phenomenon will release even larger quantities of CO2 than once supposed from organic matter in permafrost--a pool of carbon previously thought to be bound tightly and safely sequestered by iron.

The amount of stored carbon that is bound to iron and gets converted to CO2 when released is estimated to be somewhere between two and five times the amount of carbon released annually through anthropogenic fossil fuel emissions.

Iron doesn't bind organic carbon after all

Researchers have long been aware that microorganisms play a key role in the release of CO2 as permafrost melts. Microorganisms activated as soil thaws convert dead plants and other organic material into greenhouse gases like methane, nitrous oxide and carbon dioxide.

What is new, is that the mineral iron was believed to bind carbon even as permafrost thawed. The new result demonstrates that bacteria incapacitate iron's carbon trapping ability, resulting in the release of vast amounts of CO2. This is an entirely new discovery.

"What we see is that bacteria simply use iron minerals as a food source. As they feed, the bonds which had trapped carbon are destroyed and it is released into the atmosphere as greenhouse gas," explains Associate Professor Carsten W. Müller of the University of Copenhagen's Department of Geosciences and Natural Resource Management. He elaborates:

"Frozen soil has a high oxygen content, which keeps iron minerals stable and allows carbon to bind to them. But as soon as the ice melts and turns to water, oxygen levels drop and the iron becomes unstable. At the same time, the melted ice permits access to bacteria. As a whole, this is what releases stored carbon as CO2," explains Müller.

The study has just been published in Nature Communications.

Absent from climate models

Although the researchers have only studied a single bog area in Abisko, northern Sweden, they have compared their results with data from other parts the northern hemisphere and expect their new results to also be valid in other areas of permafrost worldwide.

"This means that we have a large new source of CO2 emissions that needs to be included in climate models and more closely examined," says Carsten W. Müller.

Even though carbon stored in permafrost has a major impact on our climate, researchers know very little about the mechanisms that determine whether carbon in soil is converted into greenhouse gases.

"The majority of climate research in the Arctic focuses on the amount of stored carbon and how sensitive it is to climate change. There is a great deal less of a focus on the deeper mechanisms which trap carbon in soil," says Carsten W. Müller.

Researchers remain uncertain about how much extra carbon from soil could potentially be released through this newly discovered mechanism. Closer investigation is needed.

The findings add to current knowledge of how insects fly and keep stable in the air. They could also help to inspire new designs in small aerial vehicles like drones, which can be useful for search-and-rescue attempts and building inspection.

Our colourful sunny-day companions can glide, fly backwards, and travel up to 54 km/h when hunting prey or escaping predators - but like any flying creature, they can be thrown off balance and even find themselves upside down.

Many land-based animals like cats, and aerial animals like hoverflies, rotate themselves around a head-to-tail axis when falling, known as 'rolling', but not much is known about how most insects right themselves from extreme orientations.

In a new study published today in Proceedings of the Royal Society B, Imperial College London researchers have found that unlike many animals documented to date, dragonflies most frequently perform upside down backflips, known as 'pitching', to right themselves from upside down positions in the air.

They also found that dragonflies perform the same righting maneuver whilst unconscious, suggesting the response has a large component of passive stability - a flight mechanism like that which lets planes glide when their engines are switched off. The research reveals how the shape and joint stiffness of the dragonflies' wings provide passive stability and could inform designs for small drones.

Senior author Dr Huai-Ti Lin, of Imperial's Department of Bioengineering, said: "Engineers could take inspiration from flying animals to improve aerial systems. Drones tend to rely heavily on fast feedback to keep them upright and on course, but our findings could help engineers incorporate passive stability mechanisms into their wing structure."

To conduct the study, the researchers dressed 20 common darter dragonflies with tiny magnets and motion tracking dots like those used to create CGI imagery.

They then magnetically attached each dragonfly to a magnetic platform either rightside-up or upside-down with some variations in tilt, before releasing the insects into a freefall. The motion tracking dots provided moving 3D models of the dragonfly movements, which were captured by high-speed cameras for 3D reconstruction.

They found that conscious dragonflies, when dropped from the upside-down position, somersaulted backwards to regain the rightside-up position. Dragonflies that were unconscious also completed the somersault, but more slowly.

Dead dragonflies did not perform the maneuver at all, but when their wings were posed into specific live or unconscious positions by researchers, they were able to complete the righting maneuver - albeit with a little more spin around the vertical axis than in live dragonflies. The researchers say this suggests that the maneuver relies on both muscle tone and wing posture, which is inbuilt in the dragonfly as a passive response rather than an active control.

Lead author Dr Sam Fabian, also of the Department of Bioengineering, said: "Planes are often designed so that if their engines fail, they will glide along stably rather than drop out of the sky. We saw a similar response in dragonflies, despite the lack of active flapping, meaning that some insects, despite their small size, can leverage passive stability without active control.

"Passive stability lowers the effort requirements of flight, and this trait likely influenced how dragonfly shapes evolved. Dragonflies that use passive stability in flight are likely to have an advantage, as they use less energy and are better able to recover from inconvenient events."

The researchers continue to research dragonfly flight biomechanics and will next investigate how these passive effects impact a dragonfly's active vision and guidance strategies in prey interception and obstacle avoidance.

Growing the right crop in the right place within an impaired watershed can achieve significant water quality improvements, according to Penn State researchers, who conducted a novel study in the drainage of a Susquehanna River tributary in an agricultural area in southeastern Pennsylvania.

The research may reveal a potential path for restoring the troubled Chesapeake Bay, said Patrick Drohan, associate professor of pedology in the College of Agricultural Sciences and one of the study's authors. The bay -- which long has been impaired in large part by nutrients and sediment washing off crop fields and getting into surface waters that feed it -- needs bold solutions, such as changing cropping systems, he suggested.

"Other than when wastewater treatment plants came into compliance in the Chesapeake Bay watershed, no other 'practice' has been shown to have as large an effect on nitrogen, phosphorus and sediment reductions as simply reallocating existing crop percentages to less risky landscapes," he said. "Even without additional best management practices, just moving row crops such as corn and soybeans away from streams and off steep slopes can make a huge difference."

The research -- conducted in the 52-square-mile Conewago Creek watershed that drains parts of Lancaster and Dauphin counties -- was led by Fei Jiang, a recent soil science doctoral degree graduate and current postdoctoral scholar in the Department of Entomology. Jiang deployed a powerful computer program called the Soil and Water Assessment Tool to model crop growth and losses of total nitrogen, total phosphorus and sediment for an eight-year period, from 2010-2017.

Then, based on those model results, she developed an innovative algorithm to spatially reallocate crop rotations within existing agricultural land to reduce total nitrogen, total phosphorus and sediment losses based on soil properties, while maintaining a similar production area for each rotation. Hay was reallocated onto landscapes most vulnerable to erosion and nutrient loss, whereas corn-soybean rotations were reallocated onto less vulnerable areas.

In findings recently published in Agricultural Systems, those crop reallocation simulations resulted in a 15% reduction in total nitrogen losses, a 14% reduction in total phosphorus losses and a 39% reduction in sediment losses at an average annual scale across the watershed.

Considered to be a pollution "hot spot" in the Chesapeake Bay watershed, the Conewago Creek drainage was an ideal place to perform the experiment, Jiang noted. The stream carries high nutrient and sediment loads in a watershed with a high percentage of agricultural land use. She said she hopes the study opens a dialogue that results in real improvements for the bay.

"Originally, I worried that this research will be seen as too theoretical, that farmers will never change what they grow and where they grow it, and the research wouldn't have any real meaning," she said. "But given the sharp reductions in pollution that we have shown are possible with this fresh approach, I think people will be convinced to consider giving it a try. This model is actually doable in real life."

The concept of concentrating production in certain areas and replacing existing crops with alternatives in other areas is new in the United States but has been the subject of considerable experimentation in the European Union, Drohan pointed out. In countries such as Ireland and the Netherlands, scientists are exploring the potential of a soil-based, land-use framework to achieve economic and environmental targets in agriculturally dominated watersheds.

"The agricultural norm is for farmers to dictate what, when and where to plant based on market demand and the most economically efficient use of land resources for the individual farm enterprise," he said. "The EU is exploring a different approach in impaired watersheds; however, this framework has not been tried in the United States."

The results of this study suggest that redistributing crop rotations within the Chesapeake Bay watershed might achieve needed, substantial water-quality benefits that so far have eluded policymakers implementing other practices, Drohan noted. But the devil will be in the details.

"Future research is needed to understand how this approach affects farm-level factors, because implementation may require some farmers to change the type of crops they grow and how profits are shared," he said. "Models for how farmers could cooperate exist from several different fisheries around the world -- such models are referred to as co-management strategies. Economic payment or incentive strategies, such as the EU's Common Agricultural Payment scheme, also could be explored to incentivize cooperation as an alternative to the USDA farm bill."

Bats are the only mammals that can actively fly. Some species travel over one hundred kilometres on their nocturnal excursions in search of food. Researchers at the Max Planck Institute of Animal Behavior in Radolfzell have now discovered that European free-tailed bats use uplifting winds for their ascents - a behaviour that was previously known only from birds. To do this, they tracked the bats using mini GPS loggers and then linked the flight data to weather data. The animals can thus gain altitude of well over 1,000 metres without expending much energy. The results also show that the bats reach flight speeds of up to 135 kilometres per hour.

Thanks to the development of small yet powerful GPS transmitters, researchers can accurately track the flight paths of bats. Together with colleagues from Portugal and the US, researchers from the Max Planck Institute of Animal Behavior in Radolfzell have fitted European free-tailed bats with such transmitters. The astonishing findings on the flight behaviour of these small mammals have been made possible only by the international cooperation of experts in animal behaviour, meteorology, biomechanics, and modelling.

Analysis of the GPS data has revealed that the bats often follow the natural course of the landscape and maintain the same height above the ground. However, every now and then, they literally shoot upwards only to plummet down again - a behaviour that researchers call a roller-coaster flight. The bats climb 300 to 800 metres in the process. One bat even reached a peak value of 1,680 metres above the ground.

The scientists suspect that the bats do this in order to get an overview of the landscape or look for swarms of insects. "Or maybe they are just having fun", says Teague O'Mara, lead author of the study, who is now conducting research in the US. It is easy to explain why the animals plunge down again directly after the ascent: bats cannot glide for long. Their wings are not made for that; they are too flexible and stretchy. That is why they cannot use the gain in altitude for an extended gliding flight as storks do, for example.

Obstacles cause upwinds

The ascents, during which the bats gain up to 4.5 metres of height per second, would be enormously energy-sapping for the small animals in active flight. The researchers therefore investigated whether the animals take advantage of favourable winds. This behaviour is known from some bird species (e.g. vultures and storks), which soar upwards with the help of thermal updrafts. However, thermals develop only when the sun strongly heats the ground and thus the lower layers of air. At night, the bats must therefore use other types of uplifting wind. A close analysis of the flight paths revealed that they probably use the upward movement that occurs when winds cross obstacles such as mountains and other elevations.

However, it is still unclear how the animals find these places. They may recognize favourable landscape features such as steep slopes. They could learn from their positive experiences in these places and repeatedly seek them out. "Our results are only a small, initial glimpse. But they open up an exciting new research field", explains Dina Dechmann, group leader at the Max Planck Institute in Radolfzell.

In an earlier study, she and her colleagues measured flight speeds of over 150 kilometres per hour in the smaller Mexican free-tailed bat - a result that was received with some scepticism in the research community. However, the new data measured with even better methods confirm these earlier results and indicate a similar peak value of 135 kilometres per hour for flight under their own power - speeds that, to date, are exceeded only by birds in nosedive. "We don't know how the little animals reach these astounding speeds", says O'Mara. Almost all of the power for the wing beat comes from the pectoral muscles, which are only about two centimetres long.