Culture

Scientists have discovered an essential protein in cholera-causing bacteria that allows them to adapt to changes in temperature, according to a study published today in eLife.

The protein, BipA, is conserved across bacterial species, which suggests it could hold the key to how other types of bacteria change their biology and growth to survive at suboptimal temperatures.

Vibrio cholerae (V. cholerae) is the bacteria responsible for the severe diarrhoeal disease cholera. As with other species, V. cholerae forms biofilms - communities of bacteria enclosed in a structure made up of sugars and proteins - to protect against predators and stress conditions. V. cholerae forms these biofilms both in their aquatic environment and in the human intestine. There is evidence to suggest that biofilm formation is crucial to V. cholerae's ability to colonise in the intestine and might enhance its infectivity.

"V. cholerae experiences a wide range of temperatures, and adapting to them is not only important for survival in the environment but also for the infection process," explains lead author Teresa del Peso Santos, a postdoctoral researcher at the Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Sweden. "We know that at 37 degrees Celsius, V. cholerae grows as rough colonies that form a biofilm. However, at lower temperatures these colonies are completely smooth. We wanted to understand how it does this."

The researchers screened the microbes for genes known to be linked with biofilm formation. They found a marked increase in the expression of biofilm-related genes in colonies grown at 37C compared with 22C.

To find out how these biofilm genes are controlled at lower temperatures, they generated random mutations in V. cholerae and then identified which mutants developed rough instead of smooth colonies at 22C. They then isolated the colonies to determine which genes are essential for switching off biofilm genes at low temperatures.

The most common gene they found is associated with a protein called BipA. As anticipated, when they intentionally deleted BipA from V. cholerae, the resulting microbes formed rough colonies typical of biofilms rather than smooth colonies. This confirmed BipA's role in controlling biofilm formation at lower temperatures.

To explore how BipA achieves this, the researchers compared the proteins produced by normal V. cholerae with those produced by microbes lacking BipA, at 22 and 37 degrees Celsius. They found that BipA alters the levels of more than 300 proteins in V. cholerae grown at suboptimal temperatures, increasing the levels of 250 proteins including virtually all known biofilm-related proteins. They also showed that at 37 degrees Celsius, BipA adopts a conformation that may make it more likely to be degraded. In BipA's absence, the production of key biofilm regulatory proteins increases, leading to the expression of genes responsible for biofilm formation.

These results provide new insights into how V. cholerae adapts to temperature and will help understand - and ideally prevent - its survival in different environments and transmission into humans.

"We have shown that BipA is critical for temperature-dependent changes in the production of biofilm components and alters colony shape in some V. cholerae strains," concludes senior author Felipe Cava, Associate Professor at the Department of Molecular Biology, and MIMS Group Leader and Wallenberg Academy Fellow, Umeå University. "Future research will address the effect of temperature- and BipA-dependent regulation on V. cholerae during host infection and the consequences for cholera transmission and outbreaks."

Why do genes need to be silenced? The "genes" in question are in fact transposons, selfish genetic elements that seek to self-multiply at the host's expense and that need to be controlled. Julius Brennecke's group at IMBA focuses on lifting the mysteries of a specific type of transposon silencing, namely the piRNA pathway in animal gonads. Understanding this ancient silencing system promises to reveal general mechanistic principles of gene expression and chromatin biology.

Gene silencing: either before they "speak", or right as they attempt to

Heterochromatin, a tightly packed form of DNA, plays an essential role in transposon silencing and in safeguarding eukaryotes' genomic integrity. Distinct strategies are set in motion to guarantee that heterochromatin formation be sequence specific against undesirable genetic elements, or target loci. One such strategy uses so called nuclear Argonaute proteins, which are complexed with small RNAs that guide them to nascent transposon transcripts in chromatin (i.e., transposon mRNAs still associated with the transcribing polymerase). This strategy is therefore dependent on target locus transcription and is referred to as "co-transcriptional gene silencing". One specific Argonaute protein associated with co-transcriptional gene silencing in Drosophila ovaries is Piwi, bound to short piRNAs that are encoded by genomic master loci called piRNA clusters. Piwi-mediated silencing requires heterochromatin factors (silencing effectors) to be recruited, a step that is mediated by the SFiNX complex (silencing factor interacting nuclear export variant), a complex formed of the heterodimeric nuclear RNA export variant Nxf2-Nxt1 and the Piwi-associated orphan protein Panoramix (Panx). The SFiNX complex had been previously identified by four groups in the field independently, including the Brennecke lab. For more on this topic, have a look at a previous press release on how flies repeatedly coopted nuclear export factors for genome defense: https://www.imba.oeaw.ac.at/research-highlights/upcycling-of-proteins-protects-dna-from-parasites/ .

Cut up and the two SFiNXes

The current publication in the journal Genes & Development was spearheaded by the PhD student Jakob Schnabl and unravels the molecular mechanism and function of the SFiNX complex. The researchers first identified Cut up (Ctp), the Drosophila ortholog of the highly conserved Dynein Light Chain 8 (LC8), to be a functional member of the SFiNX complex. Intriguingly, Cut up mediates SFiNX dimerization, which turns out to be essential for its molecular functionality. "In order for Piwi to be able to silence transposons, the SFiNX complex needs to be dimerized by Cut up," says IMBA group leader Julius Brennecke. Just as one hand alone does not clap, it takes two SFiNXes, brought together by Cut up, to silence!

The least expected player and a myriad of other functions yet to be dissected

Jakob Schnabl has already been involved in the 2019 publication from the Brennecke lab describing SFiNX. This earlier work was guided by PhD student Julia Batki, who received award recognitions for her thesis and who is also an author on the current SFiNX publication. When asked about Julia's contribution to the Cut up paper, Jakob's eyes light up: "Quite some part of the paper is about this small protein [Ctp/LC8, aka Cut up] that acts as a dimerization mediator for the SFiNX complex, and there I collaborated very closely with Julia". Jakob elaborates: "Honestly, we originally thought that the Dynein Light Chain [Cut up] is a contaminant in our experiments because if you look at it superficially it just doesn't make sense that a component of a cytoplasmic motor protein complex is involved in nuclear SFiNX biology. But Cut up kept coming up in our interaction screens. At some point we just had to test for it directly with the aim of ruling out a function. That experiment, however, strongly pointed to Cut up being a functional SFiNX subunit!". Jakob goes on to say "In fact, when you look more closely into the literature, you notice that this protein [Cut up] is implicated in many, many functions! It is sort of a dimerization hub protein, yet somewhat overlooked in general".

A DNA-RNA crosstalk leading to gene silencing

Finding that SFiNX is a dimer set the stage for Jakob to characterize SFiNX biochemically. Jakob could show that dimeric SFiNX is able to interact with either the DNA target locus or the nascent RNA. These two distinct interactions ultimately lead to the same goal, namely transposon silencing. The authors also showed that the SFiNX complex can form condensates in vitro in the presence of nucleic acids and used this property to assay for SFiNX's ability to form multivalent interactions. In light of the new findings, the authors propose a model to explain the SFiNX complex's function and molecular mechanism. This model of multivalent interactions would involve a SFiNX-mediated DNA-RNA crosstalk to enable other domains within SFiNX or co-recruited silencing effectors to establish heterochromatin. "In the end, a nascent transcript is a transient molecule on chromatin, and SFiNX multivalency and its ability to bind DNA and RNA seems to be a key activity to keep the nascent RNA on chromatin. This might well be a more general mechanism underlying co-transcriptional or RNA-mediated heterochromatin formation," concludes Julius Brennecke.

Combining healthy lifestyle interventions reduces heart disease through beneficial effects on different lipoproteins and associated cholesterols, according to a study published February 9 in eLife.

Having a healthy lifestyle has long been associated with a lower risk of developing heart disease. The new study provides more detailed information on how healthy lifestyles improve cholesterol, and suggests that combining cholesterol-lowering medications and lifestyle interventions may yield the greatest benefits to heart health.

Cholesterol-lowering medications such as statins help reduce heart risks by lowering levels of low-density lipoprotein (LDL) cholesterol, the so-called "bad" cholesterol. Healthy lifestyle interventions, including exercising regularly, having a healthy diet, lowering alcohol consumption and maintaining a healthy weight, have also been shown to lower LDL as well as increase "healthy" high-density lipoprotein (HDL) cholesterol.

"Until now, no studies have compared the lipid-lowering effects of cholesterol-lowering medications and healthy lifestyle interventions side by side," says lead author Jiahui Si, Postdoctoral Research Fellow in the Department of Epidemiology at Harvard T.H. Chan School of Public Health, Boston, Massachusetts, US.

To address this gap, Si and colleagues used a technique called targeted nuclear magnetic resonance spectroscopy to measure 61 different lipid markers in blood samples from 4,681 participants in the China Kadoorie Biobank, including cases of stroke, coronary heart disease and healthy individuals. They studied lipid markers in the blood of participants who had multiple healthy lifestyle habits and compared them to those of participants with less healthy habits. They found 50 lipid markers associated with a healthy lifestyle.

When the team looked at a subset of 927 individuals who had coronary heart disease in the next 10 years and 1,513 healthy individuals, they found 35 lipid markers that showed statistically significant mediation effects in the pathway from healthy lifestyles to the reduction of heart disease. Together, the combined beneficial effects of the lipid changes associated with healthy lifestyle practices were linked to a 14% reduced risk of heart disease. Specifically, very-low-density lipoprotein (VLDL) and HDL levels in the blood were linked to the heart-protecting benefits of healthy lifestyles.

"Using a genetic scoring technique, we could compare the effect of cholesterol-lowering drugs with that of lifestyle side by side in the study participants," says co-senior author Liming Liang, Associate Professor of Statistical Genetics in the Department of Epidemiology at Harvard T.H. Chan School of Public Health. "Our analysis confirmed that cholesterol-lowering drugs would have the expected effect in lowering LDL cholesterol, but this is much weaker compared to the effect of healthy behaviours on VLDL cholesterol which also increases the risk of heart disease."

Overall, they found that taking cholesterol-lowering medications and engaging in multiple healthy lifestyles would likely help individuals to achieve the greatest heart-protecting benefits because of the complementary effects of the drugs and healthy behaviours.

"Lifestyle interventions and lipid-lowering medications may affect different components of the lipid profile, suggesting they are not redundant strategies but could be combined for improved benefits," concludes co-senior author Jun Lv, Professor at the Department of Epidemiology & Biostatistics at the School of Public Health, Peking University Health Science Center, Beijing, China.

The fact that cells are motile and come into contact with each other is one of biology's fundamental principles. During embryonic development, cells must communicate with their neighbors in order to find their proper place in the differentiating organism. Wound healing is another process in which direct intercellular interactions are essential. In this context, motility enables cells to migrate to the location of the lesion and regenerate lost structures. Cancer cells also make use of this property to leave their site of origin in the primary tumor, which allows them to initiate the formation of metastatic tumors in other tissues.

"In recent years, biologists and physicists who study motility have mainly focused on investigating how large collectives comprising hundreds or thousands of cells coordinate their movements," says doctoral student David Brückner. His PhD supervisor Chase Broedersz is Associate Professor of Theoretical Biophysics at Ludwig-Maximilians-Universitaet (LMU) in Munich and the Vrije Universiteit (VU) in Amsterdam. "We wanted to know how pairs of cells interact when they come into contact, and set out to analyze their behavior using the methods of statistical physics."

Caged cells

To do so, Brückner and his colleagues fabricated a microscopic 'cage', which they refer to as a 'cell collider'. The use of defined geometries is a popular strategy in studies of cell motlity, but Alexandra Fink, a PhD student in the group led by Joachim Rädler, Professor of Biophysics and the Physics of Soft Matter at LMU, has now applied it in a novel context.

"The idea was to isolate two cells, while permitting them to interact in a restricted fashion," Brückner explains. This was achieved by placing single cells in each of two compartments that were connected by a narrow channel. This geometry meant that the cells could interact by extending thin membrane projections called protrusions, inevitably leading to collisions. The cell nuclei were labeled fluorescently to enable the movements of both cells to be monitored by fluorescence microscopy, so that the positions of the two could be tracked over time. "Based on the resulting experimental data, we were able to develop a model that provides a physical description of how the cells interact," says Brückner.

Evasive action on a microscopic scale

The observations revealed that when normal cells come into contact in the cell collider, their protrusions repel each other, and are then fully retracted. "When normal cells make contact, they tend to change direction so as to avoid the obstacle," says Brückner. This response to initial contact enables the cells to keep their distance from one another. "We were surprised to find that tumor cells behave in a very different way," Brückner adds.

In almost all cases, the two cancer cells tried to get past each other. With the aid of their theoretical model, the team was able to simulate this response in detail. The analysis revealed that, when two tumor cells approach each other they do not - as one might expect - slow down. Instead, they accelerate to squeeze past one another.

"These findings suggest two interesting approaches for further investigations," says Brückner. In the next step, the LMU team plan to identify the molecular bases for the very different interactions of the two cell types. Cancer cells are known to differ from their normal counterparts with respect to the sets of proteins exposed on their surfaces. Among them, cadherins - a specific class of proteins that play a vital role in mediating cell adhesion - are of particular interest.

Whether or not cadherins alone can account for the differences observed in the study is not yet known. In addition, the authors intend to examine whether bigger cell aggregates, such as those found in tumors, display patterns of motility similar to those exhibited by pairs of cells.

Icebergs are melting faster than current models describe, according to a new study by mathematicians at the University of Sydney. The researchers have proposed a new model to more accurately represent the melt speed of icebergs into oceans.

Their results, published in Physical Review Fluids, have implications for oceanographers and climate scientists.

Lead author and PhD student Eric Hester said: "While icebergs are only one part of the global climate system, our improved model provides us with a dial that we can tune to better capture the reality of Earth's changing climate."

Current models, which are incorporated into the methodology used by the Intergovernmental Panel on Climate Change, assume that icebergs melt uniformly in ocean currents. However, Mr Hester and colleagues have shown that icebergs do not melt uniformly and melt at different speeds depending on their shape.

"About 70 percent of the world's freshwater is in the polar ice sheets and we know climate change is causing these ice sheets to shrink," said Mr Hester, a doctoral student in the School of Mathematics & Statistics.

"Some of this ice loss is direct from the ice sheets, but about half of the overall ice loss from Greenland and Antarctica happens when icebergs melt in the ocean, so understanding this process is important.

"Our model shows that icebergs are melting at faster rates than current models assume," he said.

As well as its importance for modelling how ice sheets are changing, Mr Hester said his research will help us better understand the impact of ice melt on ocean currents.

"Ocean circulation is the reason that Britain isn't as cold as Alberta, Canada, despite being at similar latitudes," Mr Hester said.

The Gulf Stream that takes warmer water from the tropics across the Atlantic keeps western Europe milder than it otherwise would be, he said.

"That current could shut down if too much freshwater is dumped into the system at once, so it's critical we understand the process of iceberg and ice sheet melt."

Where and when the freshwater is released, and how the ocean is affected, in part depends on the speed at which icebergs melt.

Co-author Dr Geoffrey Vasil from the University of Sydney said: "Previous work incorporating icebergs in climate simulations used very simple melting models. We wanted to see how accurate those were and whether we could improve on them."

Mr Hester said their models - confirmed in experiment - and the observations of oceanographers show that the sides of icebergs melt about twice as fast as their base. For icebergs that are moving in the ocean, melting at the front can be three or four times faster than what the old models predicted.

"The old models assumed that stationary icebergs didn't melt at all, whereas our experiments show melting of about a millimetre every minute," Mr Hester said.

"In icebergs moving in oceans, the melting on the base can be up to 30 percent faster than in old models."

The research shows that iceberg shape is important. Given that the sides melt faster, wide icebergs melt more slowly but smaller, narrower icebergs melt faster.

"Our paper proposes a very simple model that accounts for iceberg shape, as a prototype for an improved model of iceberg melting," Dr Vasil said.

To test these models, the researchers developed the first realistic small-scale simulations of melting ice in salt water.

"We are confident this modelling captures enough of the complexity so that we now have a much better way to explain how icebergs melt," Mr Hester said.

Dr Vasil, who is Mr Hester's PhD supervisor, said: "Before Eric started his PhD the computational tools to model these kinds of systems didn't really exist.

"Eric took a very simple prototype and made it work wonderfully on the complex ice-melting problem."

Dr Vasil said that these methods can be applied to many other systems, including glaciers melting or the melting of frozen, saline sea ice.

"But it doesn't end there. His methods could also be used by astrobiologists to better understand ice moons like Saturn's Enceladus, a candidate for finding life elsewhere in the Solar System."

Psychotherapy for panic disorder produces good results, and the effects are lasting. That is the result from a large long-term study from Lund University in Sweden. Two years after treatment were 70 per cent of the patients clearly improved and 45 per cent were remitted.

Panic disorder is one of the most common causes of mental illness in Sweden and worldwide. Approximately 2 per cent have panic disorder. When untreated, the condition is associated with emotional distress and social isolation. Panic attacks often debut in adolescence or early adulthood and many of those affected drop out of education, jobs, and can't fulfil their life dreams.

"Many people adapt to their panic disorder by various restrictions in their daily living", says psychologist Thomas Nilsson, who conducted the study, with 221 participants over 10 years, together with research colleague Martin Svensson.

"Treatment is crucial as the disorder often leads to a downward spiral in which the margin for everyday life activities becomes increasingly narrow."

The researchers studied not only the short and long-term effects of therapy but also how treatment outcome was affected by offering the patients to choose their treatment. The options were two forms of therapy, specifically designed to treat panic disorder - a psychodynamic psychotherapy (PDT) and a cognitive behavioural therapy (CBT). One half of the patients were allowed to choose their form of therapy and the other half were randomly assigned to one or the other.

The researchers' hypothesis was that the patients offered a choice between two validated treatments would benefit from receiving their chosen form of therapy. In previous research this has been the case, and psychologists generally take patient preferences into account in treatment decision. Therefore, the researchers were surprised by the result: patients' who had chosen PDT tended to have better outcomes than those who were randomly assigned to the same treatment. However, the exact opposite applied to patients in CBT: those who were randomly assigned to CBT tended to have better outcomes than those who had actively chosen that form of treatment. So far the researchers can only speculate on the reasons for this.

"Perhaps those who chose psychodynamic therapy had a more accurate perception of what they needed", says Svensson, while pointing out that more studies are required.

However, the most important finding from the study was that both treatments had both positive and lasting results. Two years after treatment 70 per cent of the patients was clearly improved and 45 per cent were remitted.

"The patients felt better in many ways. For instance depressive symptoms, that often accompany panic disorder, were significantly reduced and quality of life improved", says Svensson.

These findings are impressive given that both treatments were as brief as 12 weeks.

Following the civil war outbreak in Syria nearly ten years ago, Israel began admitting wounded Syrians into the country for humanitarian medical treatment.

In accordance with the Israeli government's decision, the Israel Defense Forces, medical corps, health care system and hospitals in the north of the country joined together to provide medical treatment to thousands of wounded Syrians. The logistics of evacuating the injured from the battlefield and transferring them to Israeli territory was often prolonged due to the fact that Israel and Syria are defined as enemy countries.

Most of the wounded were brought to the Galilee Medical Center (GMC) in northern Israel. Some were admitted within 24 hours of injury. For others, it took as long as 14-28 days to reach Israel from the combat zone.

The delay in the commencement of treatment provided medical professionals and researchers from GMC's Ear, Nose, and Throat Ward and Department of Oral and Maxillofacial Surgery with a rare window of opportunity to observe and evaluate how this lapse in time impacted the outcome of treatment.

In a study recently published in the journal Scientific Reports, the researchers report, quite surprisingly, that patients injured in the facial bones by high-speed fire and operated on approximately 2-4 weeks after the injury suffered fewer post-operative complications compared to wounded who underwent immediate surgical treatment (within 72 hours). The researchers hypothesize that this is due to a critical period of time before surgery, which facilitates healing and formation of new blood vessels in the area of the injury and, subsequently, an improvement in the blood and oxygen supply and a reduction in the incidence of complications. Prof. Samer Srouji, member of the Azrieli Faculty of Medicine of Bar-Ilan University and Chief of the Oral and Maxillofacial Institute at GMC and lead author of the study, and colleagues coined the term Critical Revascularization Period (CRP) to explain this phenomenon.

"We believe that this benefit stems from neovascularization, the formation and repair - over time -- of blood vessels in the injured region, which improves the supply of blood and oxygen to the area and, in turn, leads to smoother healing and fewer complications following surgery," explains Prof. Srouji. "This study also highlights the important interface between bedside and basic research in the lab. We are currently working on 3D organ printing methods to develop artificial organ scaffold optimized for ideal oxygenation bone construction and rapid wound healing."

Treating the wounded civilians also provided insight into injuries caused by sniper fire and high-velocity injuries unique to a battlefield. The researchers have developed a laboratory model that simulates shooting injuries and they continue to collect and process data from the period of treatment of the wounded from the Syrian civil war.

The findings in this study may lead to a reassessment of protocols for the treatment of high-speed head and facial injuries. It is not yet possible to draw unequivocal conclusions concerning the ideal time for surgical treatment. However, the research findings indicate that delayed treatment, characterized by an opportunity for maxillofacial revascularization, can enhance surgical outcomes while simultaneously decreasing postoperative morbidity and complications.

The researchers used a biophysical method called thermal proteome profiling (TPP) to gain a comprehensive overview of which human proteins are functionally altered during SARS-CoV-2 infection. TPP monitors protein amounts and denaturation temperatures - the points at which proteins heat up so much that they lose their 3D structure. A shift in denaturation temperature indicates that a particular protein has undergone a functional change upon infection, possibly due to the virus hijacking the protein for use in its own replication.

The scientists observed that infection with SARS-CoV-2 changed the abundance and thermal stability of hundreds of cellular proteins. This included thermal stability changes in proteins required to maintain the cytoskeleton - a protein network that maintains cell shape and stability - and a group of proteins called heat shock chaperones: proteins that take care of unfolded or misfolded proteins and help them to maintain their 3D structure.

Having identified candidate proteins and cellular processes that SARS-CoV-2 may hijack to promote its replication, the scientists used drugs to inhibit some of the host proteins that SARS-CoV-2 appeared to be exploiting. This resulted in a strong reduction in viral replication in the presence of two of the tested compounds, demonstrating their potential as antiviral therapeutics. The scientists believe that other proteins they identified could be targeted in a similar way to block SARS-CoV-2 proliferation.

The study was a collaborative effort, involving the Savitski team and Typas group in EMBL Heidelberg's Genome Biology Unit, EMBL's Proteomics Core Facility, the Beltrao group at EMBL's European Bioinformatics Institute (EMBL-EBI), the Boulant lab and colleagues from Heidelberg University Hospital, the German Cancer Research Center (DKFZ), and the Technical University of Munich. As well as gaining new insights into SARS-CoV-2 biology, the researchers were also able to expand the scope of the TPP methodology by adapting it to work with infectious samples under high biosafety conditions. This enables them to quickly analyse the effects of dangerous pathogens on the cell's proteins.

Psycholinguists from the HSE Centre for Language and Brain found that when reading, people are not only able to predict specific words, but also words' grammatical properties, which helps them to read faster. Researchers have also discovered that predictability of words and grammatical features can be successfully modelled with the use of neural networks. The study was published in the journal PLOS ONE.

The ability to predict the next word in another person's speech or in reading has been described by many psycho- and neurolinguistic studies over the last 40 years. It is assumed that this ability allows us to process the information faster. Some recent publications on the English language have demonstrated evidence that while reading, people can not only predict specific words, but also their properties (e.g., the part of speech or the semantic group). Such partial prediction also helps us to read faster.

In order to access predictability of a certain word in a context, researchers usually use cloze tasks, such as The cause of the accident was a mobile phone, which distracted the ______. In this phrase, different nouns are possible, but driver is the most probable, which is also the real ending of the sentence. The probability of the word driver in the context is calculated as the number of people who correctly guessed this word over the total number of people who completed the task.

The other approach for predicting word probability in context is the use of language models that offer word probabilities relying on a big corpus of texts. However, there are virtually no studies that would compare the probabilities received from the cloze task to those from the language model. Additionally, no one has tried to model the understudied grammatical predictability of words. The authors of the paper decided to learn whether native Russian speakers would predict grammatical properties of words and whether the language model probabilities could become a reliable substitution to probabilities from cloze tasks.

The researchers analysed responses of 605 native Russian speakers in the cloze task in 144 sentences and found out that people can precisely predict the specific word in about 18% of cases. Precision of prediction of parts of speech and morphological features of words (gender, number and case of nouns; tense, number, person and gender of verbs) varied from 63% to 78%. They discovered that the neural network model, which was trained on the Russian National Corpus, predicts specific words and grammatical properties with precision that is comparable to people's answers in the experiment. An important observation was that the neural network predicts low-probability words better than humans and predicts high-probability words worse than humans.

The second step in the study was to determine how experimental and corpus-based probabilities impact reading speed. To look into this, the researchers analysed data on eye movement in 96 people who were reading the same 144 sentences. The results showed that first, the higher the probability of guessing the part of speech, gender and number of nouns, as well as the tense of verbs, the faster the person read words with these features.

The researchers say that this proves that for languages with rich morphology, such as Russian, prediction is largely related to guessing words' grammatical properties.

Second, probabilities of grammatical features obtained from the neural network model explained reading speed as correctly as experimental probabilities. 'This means that for further studies, we will be able to use corpus-based probabilities from the language model without conducting new cloze task-based experiments,' commented Anastasiya Lopukhina https://www.hse.ru/en/staff/lopukhina, author of the paper and Research Fellow at the HSE Centre for Language and Brain.

Third, the probabilities of specific words received from the language model explained reading speed in a different way as compared to experiment-based probabilities. The authors assume that such a result may be related to different sources for corpus-based and experimental probabilities: corpus-based methods are better for low-probability words, and experimental ones are better for high-probability ones.

'Two things have been important for us in this work. First, we found out that reading native speakers of languages with rich morphology actively involve grammatical predicting,' Anastasiya Lopukhina said. 'Second, our colleagues, linguists and psychologists who study prediction got an opportunity to assess word probability with the use of language model: http://lm.ll-cl.org/. This will allow them to simplify the research process considerably'.

Nature has its way of maintaining balance. This statement rightly holds true for plants that are eaten by herbivores--insects or even mammals. Interestingly, these plants do not just silently allow themselves to be consumed and destroyed; in fact, they have evolved a defense system to warn them of predator attacks and potentially even ward them off. The defense systems arise as a result of inner and outer cellular signaling in the plants, as well as ecological cues. Plants have developed several ways of sensing damage; a lot of these involve the sensing of various "elicitor" molecules produced by either the predator or the plants themselves and initiation of an "SOS signal" of sorts.

In a recently published review in the journal Trends in Plant Science, Professor Gen-ichiro Arimura from Tokyo University of Science, Japan, encapsulates the research on the herbivory-sensing mechanism of plants through elicitors. Commenting of the immense value of these elicitors, Prof. Arimura states, "This review focuses mainly on elicitors because they are timely, novel, and have potential biotechnological applications".

When the same herbivorous animal comes to eat the plant multiple times, the plant learns to recognize its feeding behavior and records the "molecular pattern" associated with it. This is termed "herbivore-associated molecular patterns" or HAMPs. HAMPs are innate elicitors. Other plant elicitors include plant products present inside cells that leak out because of the damage caused by herbivory. Interestingly, when an herbivorous insect eats the plant, the digestion products of the plant cell walls and other cellular components become part of the oral secretions (OS) of the insect, which can also function as an elicitor!

Prof. Arimura highlights the fact that with the advancement of high-throughput gene- and protein-detecting systems, the characterization of elicitors of even specific and peculiar types of herbivores, such as those that suck cell sap and do not produce sufficient amounts of OS, has become possible. The proteins present in the salivary glands of such insects could be potential elicitors as they enter the plant during feeding. He explains, "RNA-seq and proteomic analyses of the salivary glands of sucking herbivores have led to the recent characterization of several elicitor proteins, including a mucin-like salivary protein and mite elicitor proteins, which serve as elicitors in the leaves of the host plants upon their secretion into plants during feeding."

The review also highlights some peculiar elicitors like the eggs and pheromones of insects that plants can detect and initiate a defense response against. In some special cases, the symbiotic bacteria living inside the insect's gut can also regulate the defense systems of the plants.

And now that we have understood different types of elicitors, the question remains--what signaling mechanisms do the plants use to communicate the SOS signal?

So far, it has been hypothesized that the signaling is made possible by proteins transported through the vascular tissue of plants. Interestingly, there is evidence of airborne signaling across plants, by a phenomenon called "talking plants." Upon damage, plants release volatile chemicals into the air, which can be perceived by neighboring plants. There is also evidence of epigenetic regulation of defense systems wherein plants maintain a sort of "genetic memory" of the insects that have attacked them and can fine-tune the defense response accordingly for future attacks.

Given the improvement in knowledge of the mechanisms of plant defense systems, we can embrace the possibility of a "genetic" form of pest control that can help us circumvent the use of chemical pesticides, which, with all their risks, have become a sort of "necessary evil" for farmers. This could usher in modern, scientifically sound ways of organic farming that would free agricultural practices from harmful chemicals.

It is almost ten years since the scientific journal Science called optogenetics the "breakthrough of the decade". Put simply, the technique makes it possible to control the electrical activity of cells with pulses of light. With its help, scientists can gain new insights into the functioning of nerve cells, for example, and thus better understand neurological and psychiatric diseases such as depression and schizophrenia.

Established procedure on animal cells

In research on animal cells, optogenetics is now an established technique used in many fields. The picture is different in plant research: transferring the principle to plant cells and applying it widely has not been possible until now.

However, this has now changed: Scientists at the Julius Maximilians University of Würzburg (JMU) have succeeded in applying optogenetic methods in tobacco plants. They present the results of their work in the current issue of the journal Nature Plants. "In particular, Dr. Kai Konrad from Prof. Hedrich's group (Botany I) and Dr. Shiqiang Gao from my group were mainly responsible for the success of this project" explains Professor Georg Nagel, co-founder of optogenetics. In addition to the Department of Neurophysiology in the Institute of Physiology, three chairs of the Julius-von-Sachs Institute were involved in the collaboration: Botany I, Botany II and Pharmaceutical Biology.

Light switch for cell activity

"Optogenetics is the manipulation of cells or living organisms by light after a 'light sensor' has been introduced into them using genetic engineering methods. In particular, the light-controlled cation channel channelrhodopsin-2 has helped optogenetics achieve a breakthrough," says Nagel, describing the method he co-developed. With the help of channelrhodopsin, the activity of cells can be switched on and off as if with a light switch.

In plant cells, however, this has so far only worked to a limited extent. There are two main reasons for this: "It is difficult to genetically modify plants so that they functionally produce rhodopsins. In addition, they lack a crucial cofactor without which rhodopsins cannot function: all-trans retinal, also known as vitamin A," explains Dr. Gao.

Green light for plant cells

Prof. Nagel, Dr. Gao, Dr. Konrad, and colleagues have now been able to solve both problems. They have succeeded in producing vitamin A in tobacco plants by means of an introduced enzyme from a marine bacterium, thus enabling improved incorporation of rhodopsin into the cell membrane. This allows, for the first time, non-invasive manipulation of intact plants or selected cells by light via the so-called anion channel rhodopsin GtACR1.

In an earlier approach, plant physiologists from Botany I had artificially added the much-needed cofactor vitamin A to cells to allow a light-gated cation channel to become active in plant cells (Reyer et al., 2020, PNAS). Using the genetic trick now presented, Prof. Nagel and colleagues have generated plants that produce a special enzyme in addition to a rhodopsin, called dioxygenase. These plants are then able to produce vitamin A - which is normally not present in plants - from provitamin A which is abundant in the plant chloroplast. The combination of vitamin A production and optimization of rhodopsins for plant application ultimately led the researchers led by Prof. Nagel, Dr. Konrad and Dr. Gao to success.

New approach for plant research

"If you irradiate these cells with green light, the permeability of the cell membrane for negatively charged particles increases sharply, and the membrane potential changes significantly," explains Dr. Konrad. In this way, he says, it is possible to specifically manipulate the growth of pollen tubes and the development of leaves, for example, and thus to study the molecular mechanisms of plant growth processes in detail. The Würzburg researchers are confident that this novel optogenetic approach to plant research will greatly facilitate the analysis of previously misunderstood signaling pathways in the future.

A pioneer of optogenetics

Rhodopsin is a naturally light-sensitive pigment that forms the basis of vision in many living organisms. The fact that a light-sensitive ion pump from archaebacteria (bacteriorhodopsin) can be incorporated into vertebrate cells and function there was first demonstrated by Georg Nagel in 1995 together with Ernst Bamberg at the Max Planck Institute for Biophysics in Frankfurt. In 2002/2003, this proof was then also achieved with light-sensitive ion channels from algae.

Together with Peter Hegemann, Nagel demonstrated the existence of two light-sensitive channel proteins, channelrhodopsin-1 and channelrhodopsin- 2 (ChR1/ChR2), in two papers published in 2002 and 2003. Crucially, the researchers discovered that ChR2 elicits an extremely rapid, light-induced change in membrane current and membrane voltage when the gene is expressed in vertebrate cells. In addition, ChR2's small size makes it very easy to use.

Nagel has since then received numerous awards for this discovery, most recently in 2020 - together with two other pioneers of optogenetics - the $1.2 million Shaw Prize for Life Sciences.

PLYMOUTH MEETING, PA [February 16, 2021] -- New research in the February 2021 issue of JNCCN--Journal of the National Comprehensive Cancer Network examined body mass index (BMI) data for people with HER2-positive early breast cancer, and found a 5% weight loss in patients over two years in was associated with worse outcomes. Weight gain over the same time period did not affect survival rates.

"The finding that weight loss, and not weight gain, was associated with worse outcomes is unexpected," said lead researcher Samuel Martel, MD, Universitè de Sherbrooke, Quebec, Canada, who worked with researchers in Belgium, Brazil, Germany, Italy, Switzerland, and the United Kingdom, as well as the National Cancer Institute and the Mayo Clinic in the United States. "We were unable to make a distinction between intentional versus unintentional weight loss, so it's a matter of speculation whether worse outcomes were due to weight loss, or vice versa. We hope our findings highlight the importance of incorporating consecutive and prolonged data collection on weight in oncology trials, and gaining greater understanding of the metabolic processes after cancer diagnosis that may impact outcomes."

The BMI data came from the ALTTO BIG 2-06 trial, which collected height and weight data in 8,381 patients with HER2-positive early breast cancer treated with chemotherapy plus trastuzumab and/or lapatinib. 2.2% were underweight at the start of treatment, 45.3% were normal weight, 32.1% were classified as overweight, with another 20.4% obese--defined as a BMI greater than 30. Initial obesity was associated with worse outcomes, including more frequent and serious adverse events leading to treatment discontinuation, as well as significantly worse overall survival rates.

"It was surprising to see that more than 5% weight loss at 2 years was associated with poorer distant disease-free survival. Is our general advice to obese/overweight patient to exercise and lose weight wrong?" questioned Anthony D. Elias, MD, University of Colorado Cancer Center, a member of the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Panel for Breast Cancer. "Careful examination of the Kaplan-Meier hazard plots suggests that the relapse curves for those with weight loss are steeper in the second and third years of follow-up, but thereafter are relatively parallel. It's possible that the weight loss observed early may be an indication for impending relapse of breast cancer."

The study highlights the importance of weight management in cancer survivorship. The authors hope their findings may provide the basis for further research and oncology trials to guide weight control during the survivorship period.

High levels of public support for strict measures to control COVID-19 during the first wave of the pandemic did not reflect high levels of public trust in the UK government's honesty, transparency or motives, suggests a new study published in PLOS One.

The 'mixed-methods' project, a collaboration between the London School of Hygiene & Tropical Medicine (LSHTM) and University College London (UCL), involved collecting data from more than 9,000 adults living in the UK using an online survey.

It found that during the first wave of COVID-19 (April 2020) 95% of participants were in support of the government having powers to enforce behaviour change. However, only around half (52%) thought that the government was actually doing a good job of controlling COVID-19. Even fewer (36%) thought the government "always or mostly" told the truth about COVID-19.

The study brought together scientists from many disciplines including outbreak specialists, anthropologists, data scientists and epidemiologists. The team asked people to talk about their experiences of lockdown in their own words and then, using sophisticated machine learning approaches, identified where participants talked about topics that related to trust and transparency.

The team's social scientists then read the responses to piece together how people's attitudes towards lockdown related to their perspectives on how trustworthy, truthful and transparent they felt the UK government was being about COVID-19 and the response.

Against a backdrop of relatively low opinions of the UK government's honesty and transparency, the team was surprised to find many of the study's participants still supported the implementation of strict measures to force people to comply with control guidelines. Many even said that they felt there were times when it was justifiable, or even necessary for the government to be less than fully open.

Dr Luisa Enria, Assistant Professor at LSHTM and primary author of the study, said: "In times of crisis and insecurity, citizens may be willing to accept lower levels of transparency for the sake of national security. But if this is a crisis effect that is driven by sudden dramatic changes and a climate of fear and uncertainty, then this is not something that the government can necessarily rely on in the long term to maintain confidence in, and support for control guidelines."

Previous work by Dr Enria and the study's co-lead investigator Professor Shelley Lees has shown that the success of outbreak responses is closely linked to the strength of public trust.

Professor Lees from LSHTM said: "Our work in communities affected by Ebola Virus in West Africa and DR Congo has shown that if the public doesn't trust the people leading the response, and if there are perceptions that those leaders lack transparency and honesty; then this can hamper control of the infection."

The project also looked at how levels of trust differed among communities from around the UK. Compared with those living in London, Scottish respondents had significantly lower levels of trust, whilst people from the West Midlands, East and South East of England all had significantly higher levels of trust.

Groups that had lower levels of household income, or who had higher levels of education such as a degree, were each around half as likely to trust the government as people at the other ends of the spectrum. Among the 48% of respondents who felt that the government was not making good decisions, a significant majority (60%) felt that the economy was being prioritised. Only around 5% thought that people and their health were the main priority for the government.

In the group who thought that the government was doing well, those figures were very different (respectively 10% and 32%). Despite efforts to distribute the survey to black and minority ethnic groups, the study team had a very low response and cautioned that further work was needed to understand issues of trust among members of these and other minority communities.

Dr Enria said: "Many of our respondents expressed concerns about the extent to which scientific evidence was really being used to guide policy. The consistency of communications from the government, the lack of insight into how policy decisions were being made, and about what were the government's real motivations, were also concerns of many people surveyed.

"These are questions we've come to hear a lot over the last year, but they were already being asked a year ago at the beginning of wave one."

The research team recommend that the UK government should develop targeted community engagement measures and tailor their messaging and public discussion to the realities faced by particular groups across the political, social and economic divides.

In contrast to the centralised and top-down communication so far, the team believes that this approach could directly address the diversity of experiences and perspectives that exist across the country, and help to maintain support and adherence to government guidelines.

Dr Chrissy Roberts, Associate Professor at LSHTM and the study's co-lead investigator, said: "We know from the lessons of past epidemics that public consent for control measures, meaning the willingness of people to follow the rules, can just evaporate when trust is gone. The government can't depend on crisis effects forever, nor ignore the hard to reach groups when trying to encourage good infection prevention and control behaviours.

"They have to gain the trust of every group. This means reaching out to, opening dialogues with, and engaging in constructive collaborations with people and communities outside their normal sphere of political and social influence."

The authors acknowledge limitations of the study, including that the survey was not population representative, meaning that the findings could not be generalised across all communities and demographic groups in the UK. There was over-representation of white, female and more highly educated people in the survey and significant under-representation of black, Asian and minority ethnic people. The study team emphasised the importance of exploring the political consequences of epidemic control measures in the contexts of structural inequality and lack of equity for ethnic and cultural minorities.

A recent qualitative study sheds light on how people cope with health and financial challenges, highlighting the important role that communication plays in these coping strategies.

"This is one of the first studies to look at how people respond to the combination of financial uncertainties and health uncertainties," says Lynsey Romo, first author of the study and an associate professor of communication at North Carolina State University. "And it drives home that uncertainty about money and uncertainty about health go hand in hand. Financial limitations created significant health challenges - such as an inability to afford prescription medications. And health problems created significant expenses leading to serious financial challenges.

"The study also highlights that these challenges span income levels. You can have a good job, good insurance, do everything 'right' and still find yourself struggling due to the nature of the healthcare system in the U.S."

For the study, researchers conducted in-depth interviews of 17 U.S. adults. All were white; 14 identified as women. Study participants had medical debt ranging from less than $10,000 to more than $150,000. Salaries also ranged from less than $10,000 to more than $150,000. The health problems that resulted in financial struggles included conditions such as cancer, cystic fibrosis and stroke.

The researchers found that health-related financial uncertainty had significant adverse consequences for the physical and mental health of many study participants. For example, many interviewees reported experiencing symptoms of emergent depression and other mental health issues related to their health conditions and related financial challenges.

As one study participant noted: "It gets to the point where [the financial uncertainty] just weighs against you. Like, am I worth doing this procedure?...I'll never make this much money. I'm never going to be able to pay this off."

The researchers discovered a range of strategies that study participants utilized to manage their uncertainty.

"Many of these strategies revolved around communication," Romo says. "Seeking information and emotional support from your social network is inherently about communication. Seeking financial help or help in getting to medical appointments is about communication. Advocating for yourself or others in the context of medical care is all about communication. So being able to share information effectively is incredibly important."

Other strategies for managing uncertainty involved making sacrifices - and provided clear examples of the impact that uncertainty can have on physical health.

For example, study participants reported buying less food in order to afford medication; being unable to afford medications at all; taking less medication than a doctor prescribed in order to make it last longer; being unable to attend health appointments due to cost.

"Qualitative studies, like this one, are important," Romo says. "There are lots of statistics about how many people are struggling with medical debt. I remember seeing survey data from early last year showing that more than 30% of U.S. workers carry medical debt - and that was looking at people with jobs, before the pandemic.

"Qualitative studies give us a fuller understanding of what those numbers mean in real-world terms. What effect does this combination of financial and health uncertainty have on people? And how do they deal with it? Our study suggests that the effect is profound. The pandemic, and related expenses, may make it worse. And this is something we need to be looking at."

By Maria Fernanda Ziegler | Agência FAPESP – The use of cover crops between cotton harvests protects the soil, conserves water, and reduces the risk of erosion. Researchers at the University of Western São Paulo (UNOESTE) and São Paulo State University (UNESP) in Brazil found that application of potassium (K) to a grass cover crop grown before cotton in sandy soil lowered production cost and resulted in cotton with a higher market value.

“The dynamics of early application of potassium to grass planted as a cover crop before cotton results in more resistant fibers and a smaller proportion of short fibers than when the conventional method of applying the nutrient to the cotton crop is used. In addition to the improvement in quality, the technique reduces production cost for the farmer because of its impact on operational dynamics. The farmer can apply potassium once instead of twice. The technique saves labor and diesel oil, as well as optimizing operational logistics. In the long run, it’s also expected to reduce fertilizer use,” said Fábio Echer, a professor at UNOESTE and lead author of an article on the study published in Scientific Reports.

The two-year study, which was conducted on UNOESTE’s experimental farm, compared the conventional method of fertilizing cotton directly with two other methods, both involving early application of potassium. It also evaluated cotton growing without fertilizer and without a cover crop.

The research was funded by a master’s scholarship awarded by FAPESP to Vinicius José Souza Peres. The São Paulo State Cotton Growers Association (APPA) and Fundação Agrisus also collaborated on the project.

Quantitative and qualitative analysis of fiber

In one of the treatments, the researchers applied potassium to the grass cover crop in two doses (70 kg per hectare each). They compared this with application to the cover crop of a single dose of 140 kg per hectare and split application, with half going to the cover crop and the other half to the cotton. The results in terms of fiber yield were identical to those of the conventional method. Yield and quality were both lower with no fertilizer than when the conventional method or early application was used.

“The study included a calculation of fertilizer use efficiency,” Echer told Agência FAPESP. “We found that early application enabled the forage grass used as a cover crop to recover nutrients from the soil, in addition to the function of protecting it. This plant has a deep rhizosphere and its roots are able to find soil nutrients lost via leaching from previous crops, recycling them, and pushing them back to the surface. When the plant dries out, it releases potassium in the first rain to the crops that come next.”

The main advantage of early application, however, is that it increases the commercial value of the cotton produced. The analysis of fiber quality and cotton value found that fertilizing the cover crop with potassium led to a smaller proportion of short fibers, which depreciate the finished product, and also enhanced fiber fineness (micronaire), maturity and strength. “These characteristics are important. They represent higher commercial value for the production of finer cotton fabric, which is better quality and fetches a higher price on the market,” Echer said.

The improvement in quality relates to the availability of potassium in the soil and plant water status. “Cotton fiber is a cell, and like all cells it needs water to expand. By conserving more water in the soil and in the plant, we can also improve fiber size,” he explained.

Potassium plays a key role in the control of plant water loss. It regulates stomata functioning, carbon dioxide fixation, enzyme activation, and nutrient transport, as well as aiding stress tolerance. Soil potassium reaches plant roots mainly by diffusion, which accounts for 72%-96% of each plant’s requirement.

“Extreme weather events, high temperatures, and droughts have become more frequent because of global warming, and conservationist soil management techniques such as those suggested by the study can mitigate the adverse effects of all this on production,” Echer said. “Inconsistent rainfall may limit crop viability, and because only about 8% of Brazil’s cotton plantations are irrigated, the use of a cover crop is especially important. Straw mulch helps reduce soil temperature, which in turn helps conserve water.”

In western São Paulo, where the experimental farm used in the study is located, the temperature can reach 70°C on cotton plantations without a cover crop (and hence with exposed soil). The use of a cover crop keeps the soil at about 28°C-30°C, conserving soil moisture.

Early application of potassium is widely used in plantations with clayey soil, Echer added, but the technique had not yet been tested on sandy soil with little organic matter, making nutrient retention harder. “Farmers were reluctant to apply fertilizer early in the case of crops planted in sandy soil,” he said. “The study proves that applying potassium to the cover crop maintains yield and improves fiber quality even in sandy soil, which is more fragile, stores less water and makes potassium more susceptible to leaching.”

According to the researchers, the method analyzed in western São Paulo can be replicated in cotton plantations with sandy soil in Mato Grosso (the leading cotton producer in Brazil) and Bahia, as well as in other countries. “The cover crop can be different from the one we used in this study, because the climate may be different, but a precedent has been set for testing new cover species in other parts of the world,” Echer said.

The article “Potassium application to the cover crop prior to cotton planting as a fertilization strategy in sandy soils” (doi: 10.1038/s41598-020-77354-x) by Fábio Rafael Echer, Vinicius José Souza Peres and Ciro Antonio Rosolem can be read at: www.nature.com/articles/s41598-020-77354-x.

Journal

Scientific Reports

DOI

10.1038/s41598-020-77354-x