Culture

Bottom Line: The U.S. Preventive Services Task Force (USPSTF) recommends that adults ages 45 to 75 be screened for colorectal cancer, lowering the age for screening that was previously 50 to 75. The USPSTF also recommends that clinicians selectively offer screening to adults 76 to 85 years of age. Colorectal cancer is the third leading cause of cancer death for both men and women in the United States. In 2016, 26% of eligible adults had never been screened and nearly one-third were not up to date with screening in 2018. The USPSTF routinely makes recommendations about the effectiveness of preventive care services and this statement replaces its 2016 recommendation.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2021.6238)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Note: More information about the U.S. Preventive Services Task Force, its process, and its recommendations can be found on the newsroom page of its website.

CLEVELAND - According to new study results, a team of researchers led by Cleveland Clinic's Thaddeus Stappenbeck, M.D., Ph.D., have found that a diet high in fat and sugar is associated with impaired intestinal immune cell function in mice. The findings, published in Cell Host & Microbe, provide novel insights into pathways linking obesity and disease-driving gut inflammation, and have implications for developing targets to treat inflammatory bowel diseases (IBD) in patients.

Using data from more than 900 patients, the researchers found that elevated body mass index is associated with abnormal Paneth cells among patients with Crohn's disease and non-IBD patients.

Paneth cells are a type of anti-inflammatory immune cell found in the intestines that helps to protect against microbial imbalances and infectious pathogens. Dysfunction of these cells is driven by a combination of genetic mutations and environmental factors. Dr. Stappenbeck and others have previously linked Paneth cell dysfunction to gut changes indicative of IBD in preclinical models and a subset of Crohn's disease patients from multiple cohorts around the world.

"With this understanding, we set out to investigate whether diet-induced obesity--specifically caused by a diet high in fat and sugar, or a 'western diet'--is one of the environmental factors that can lead to impaired Paneth cell function," said Dr. Stappenbeck, chair of Lerner Research Institute's Department of Inflammation & Immunity.

The researchers compared the effects of a western diet versus a standard diet. The team's western diet contained about 40 percent fat and an elevated level of simple carbohydrates, which better resembles the diet of an average U.S. adult than regimens prescribed in other preclinical studies.

After eight weeks, the group that ate the western diet had more abnormal Paneth cells than the group that ate a standard diet. In the western diet group, other changes become apparent two months after the Paneth cell defects, including increased gut permeability, where bacteria and toxins can enter the gut and which is well-linked with chronic inflammation. Notably, however, switching to a standard diet from the western diet completely reversed the Paneth cell dysfunction.

"When we started to look into large-scale datasets for the specific mechanisms that might connect the high-fat, high-sugar diet with the Paneth cell dysfunction, a secondary bile acid called deoxycholic acid caught our attention," said Dr. Stappenbeck.

Deoxycholic acid is a metabolic byproduct of intestinal bacteria. Researchers found that consuming a western diet increased the bile acid in a region of the intestines called the ileum and, as a result, increased the expression of two downstream molecules, farnesoid X receptor (FXR) and type I interferon (IFN).

"For the first time, we showed how coordinated elevation of FXR and type I IFN signals in multiple cell types contribute to Paneth cell defects in response to a diet high in fat and sugar. In previous research, stimulating FXR has shown to help treat other diseases, including fatty liver disease, so we are hopeful that with additional research we can interrogate how the combination of elevated FXR and IFN signals can be targeted to help treat diet-induced gut infections and chronic inflammation."

Dr. Stappenbeck also explained that while the team was interested to learn that changing the diet regimen reversed the pathological changes, more research would be needed to determine if these changes also occur in patients.

Researchers have identified specific influenza targets that could be used to better protect Indigenous people from experiencing severe influenza disease through a universal, T cell-based vaccine.

In a collaboration with Monash Biomedicine Discovery Institute, Menzies School of Health Research and CQUniversity, Peter Doherty Institute for Infection and Immunity (Doherty Institute) researchers took a deep-dive look into how the immune system can protect Aboriginal and Torres Strait Islander people from severe influenza disease.

"We know that some populations are at high risk from severe influenza, and these include Indigenous people globally," said University of Melbourne Professor Katherine Kedzierska, Laboratory Head at the Doherty Institute.

"As many as 10 to 20 per cent of Aboriginal and Torres Strait Islander people died of influenza during the 1919 pandemic, compared to less than one per cent mortality rate in non-Indigenous Australians. Hospitalisation and morbidity rates were also higher for Aboriginal and Torres Strait Islander people during the 2009 H1N1 pandemic.

"Similarly, high adult mortalities (up to 100 per cent) were reported in some isolated Alaskan villages. Our research aims to harness immune responses to protect these high-risk populations."

The research team particularly focused on killer T cells and proteins called HLAs, important in determining immune responses to different pathogens.

HLA proteins vary across individuals and ethnicities. A specific HLA protein, named HLA-A*24:02, can be linked to more severe (or even fatal) outcomes of influenza. It is also highly prevalent in Aboriginal and Torres Strait Islander people, as well as many other Indigenous populations around the world.

Using state-of-the-art antigen discovery technology at Monash University, Professor Anthony Purcell and Dr Patricia Illing identified small fragments of influenza (peptide antigens) that were subsequently screened by Dr Luca Hensen, a research officer at the Doherty Institute, who identified which of these fragments formed protective targets for killer CD8 T cells that are presented by HLA-A*24:02.

"We propose that a universal influenza vaccine could be developed using these targets to promote optimal killer CD8 T cell response in the context of HLA-A*24:02," Dr Hensen said.

"This could provide much better global protection and help prevent severe influenza disease and death in populations who are at higher risk."

Co-author, Associate Professor Steven Tong, Royal Melbourne Hospital Infectious Diseases Physician and Co-Lead of the Clinical Research Discipline at the Doherty Institute, said other factors that contribute to poorer outcomes in Indigenous populations need to be considered, including higher rates of chronic diseases and the importance of social determinants of health.

"These findings are a significant step forward in understanding the immune profile of Aboriginal and Torres Strait Islander people and enable us to put that in context with the other determinants contributing to a higher risk of severe influenza. It is critical that future T cell-based influenza vaccines are designed to also protect ethnic populations who experience a high burden of disease," Associate Professor Tong said.

CQUniversity researcher, Professor Adrian Miller, of the Jirrbal people of North Queensland, said Aboriginal and Torres Strait Islander people were some of the most vulnerable when it came to influenza.

"The spread of influenza poses particular risks for isolated Indigenous communities," Professor Miller said.

"We hope that the findings from this research ultimately lead to a universal flu vaccine that will also protect Indigenous populations."

This project looked at samples from 127 participants from the LIFT (Looking Into influenza T-cell immunity) cohort based in the Northern Territory.

Manufactured in a new process based on crystalline materials, these low-loss mirrors promise to open up completely new application areas, for example in optical respiratory gas analysis for early cancer detection or the detection of greenhouse gases. This work will be published in the current issue of the journal Optica.

In 2016 researchers at the LIGO laser interferometer succeeded in the first direct observation of gravitational waves, which had originally been predicted by Albert Einstein in 1916. A significant contribution to the observation of this wave-like propagation of disturbances in space-time, which was rewarded with the Nobel Prize a year later, was provided by the laser mirrors of the kilometer-long interferometer assembly. Optimization of these mirrors for extremely low optical absorption losses was a key advancement in realizing the sensitivity necessary to make such measurements. "Low-loss mirrors are a key technology for many different research fields," explains Oliver H. Heckl, head of the Christian Doppler Laboratory for Mid-IR Spectroscopy and Semiconductor Optics, "They are the link for such diverse research fields as cancer diagnosis and gravitational wave detection."

In fact, comparable mirror properties are also promising technological breakthroughs for significantly more practical applications. This includes, among other things, sensitive molecular spectroscopy, i.e. the detection of the smallest amounts of substances in gas mixtures - a research focus of the Christian Doppler Laboratory (CDL). Examples can be found in the early detection of cancer through the detection of the smallest concentrations of marker molecules in the breath of patients, or in the precise detection of methane leaks in large-scale natural gas production systems in order to limit the contribution of such greenhouse gases to climate change.

Unlike the experiments at LIGO, however, such investigations are conducted much further outside the visible light spectrum, in the mid-infrared range. In this wavelength region, also known as the "fingerprint region", many structurally similar molecules are clearly distinguishable on the basis of their characteristic absorption lines. Therefore, it is a longstanding wish of the photonics community, to realize similarly low loss levels in this technically challenging wavelength range.

This is exactly what the team led by Oliver H. Heckl has now achieved in an international cooperation. In this case, low loss means that the new type of mirror absorbs less than 10 out of a million photons. For comparison: A commercially available bathroom mirror "destroys" around ten thousand times more photons, and even the mirrors used in top research have ten to a hundred times higher losses.

This drastic improvement was made possible through the use of a completely new optical coating technology: First, single-crystal stacks of high-purity semiconductor materials are deposited via an epitaxial growth process. These monocrystalline multilayers are then transferred via a proprietary bonding process onto curved silicon optical substrates, completing the mirrors that were tested at both the CDL and NIST. This unique "crystalline coating" technology was developed and carried out by the industrial partner of the Christian Doppler Laboratory, Thorlabs Crystalline Solutions. This company was originally founded under the name Crystalline Mirror Solutions (CMS) in 2013 as a spin-off from the University of Vienna by Garrett Cole and Markus Aspelmeyer. CMS was acquired by Thorlabs Inc. in December 2019. This industry collaboration was made possible, with the support of the Federal Ministry for Digital and Economic Affairs, via the internationally unique model of the Christian Doppler Research Association (CDG) to promote application-oriented basic research. A research group led by Adam Fleisher from the National Institute for Standards and Technology (NIST) in Gaithersburg, Maryland (USA), which is renowned for precision measurements, also played a key role in this success. Georg Winkler, co-author of the current study expresses his enthusiasm: "Precise measurement technology is much more than just pedantry. Wherever you can take a closer look by an order of magnitude, you usually discover completely new phenomena, just think of the invention of the microscope and telescope!"

In fact, this assessment has already proven true in the detailed characterization of the new mirrors themselves, when a previously unknown effect of polarization-dependent absorption was discovered in the semiconductor layers and theoretically explored by collaborator Prof. Hartwin Peelaers at the University of Kansas. "These results open up great opportunities regarding further refinement of these mirrors ", co-author Lukas Perner is delighted: "Thanks to the extremely low losses can we now further optimize the bandwidth and reflectivity."

With this in mind, the project partners are already working on a further improvement of the technology: Expansion of the optical bandwidth of the mirrors will allow them to be used efficiently with so-called optical frequency combs. This will enable the analysis of particularly complex gas mixtures with unprecedented accuracy.

Spintronics is an emerging technology for manufacturing electronic devices that take advantage of electron spin and its associated magnetic properties, instead of using the electrical charge of an electron, to carry information. Antiferromagnetic materials are attracting attention in spintronics, with the expectation of spin operations with higher stability. Unlike ferromagnetic materials, in which atoms align along the same direction like in the typical refrigerator magnets, magnetic atoms inside antiferromagnets have antiparallel spin alignments that cancel out the net magnetization.

Scientists have worked on controlling the alignment of magnetic atoms within antiferromagnetic materials to create magnetic switches. Conventionally, this has been done using a 'field-cooling' procedure, which heats and then cools a magnetic system containing an antiferromagnet, while applying an external magnetic field. However, this process is inefficient for use in many micro- or nano- structured spintronics devices because the spatial resolution of the process itself is not high enough to be applied in a micro- or nano-scale devices.

"We discovered that we can control the antiferromagnetic state by simultaneously applying mechanical vibration and a magnetic field," says Jung-Il Hong of DGIST's Spin Nanotech Laboratory. "The process can replace the conventional heating and cooling approach, which is both inconvenient and harmful to the magnetic material. We hope our new procedure will facilitate the integration of antiferromagnetic materials into spintronics-based micro- and nano-devices."

Hong and his colleagues combined two layers: a cobalt-iron-boron ferromagnetic film on top of an iridium manganese antiferromagnetic film. The layers were grown on piezoelectric ceramic substrates. Combined application of mechanical vibration and a magnetic field allowed the scientists to control the alignments of magnetic spins repeatedly along any direction desired.

The team aims to continue the search and development of new magnetic phases beyond conventionally classified magnetic materials. "Historically, new material discovery has led to the development of new technologies," says Hong. "We want our research work to be a seed for new technologies."

In today's plants, photorespiration dissipates some of the energy produced by photosynthesis and releases CO2. It begins when the enzyme RuBisCO acts on oxygen instead of carbon dioxide and creates toxic side-products requiring costly recycling reactions. The detoxification process uses up fixed carbon and wastes energy, thus strongly limiting agricultural productivity.

Scientists generally pursue two approaches to minimizes the deleterious effects of photorespiration: mimic the carbon concentrating mechanism of C4 plants or introduce new metabolic pathways to bypass the photorespiration.

Researchers led by Andreas Weber from Heinrich Heine University Düsseldorf and Tobias Erb from the Max Planck Institute for terrestrial Microbiology have developed a solution that synergistically couples photorespiration and C4 metabolism, connecting two of the main targets in plant metabolism. Within the EU-funded project Gain4Crops (http://www.gain4crops.eu), they have turned a photorespiration bypass route, the recently discovered BHAC, into a carbon strengthening mechanism in C3 plants. The team has introduced enzymes from the microbial BHAC pathway in a model plant, Arabidopsis thaliana, where they successfully convert a product of photorespiration into the source of a synthetic C4 cycle and without dissipating carbon, nitrogen, or energy.

After a successful plant transformation, gas exchange measurement and metabolites profiling confirmed that the plant conserves nitrogen and accumulates signature C4 metabolites. The Arabidopsis model showed no gain in the amount of CO2 assimilated via photosynthesis at the expense of the CO2 released by photorespiration; but, as the team pointed out, several bottlenecks might be responsible for masking the full potential of the BHAC pathway.

To fully appreciate the gain in carbon fixed and ultimately in yield, the pathway needs to be improved by identified other targets via kinetic and genomic scale metabolic models. Indeed, prototyping in many model organisms, like Arabidopsis, allows identifying shortcomings before moving to a target crop, thus speeding up the development process. For example, the Gain4crops project plans to test the newly discovered pathway in a set of model organisms of increasing cellular and anatomical complexity before moving to its final target: the sunflower.

Overall this study represents the first proof of concept for carbon-concentrating mechanisms in C3 plant that dependent on photorespiration, coupling the solution with the problem, and creating opportunities for improved agricultural productivity in the future. Furthermore, higher photosynthetic crops might become a valuable tool in the face of climate change thanks to their climate resilience and reduced consumption of resources.

Agriculture needs to keep pace with a growing population on a planet in a short supply of resources and with changing environmental conditions. "Improving sustainability is probably the biggest challenge of the 21st century, and, even if there is no single silver bullet, the combination of different solutions might bring an effective improvement," says Andreas Weber. And in the quest for more sustainable agriculture, agriculture that uses less land and resources engineered crops that tackle photorespiration might be part of the solution.

In a recent research, researchers led by Prof. ZHANG Haimin from the Institute of Solid State Physics of the Hefei Institutes of Physical Science (HFIPS) realized the synthesis of Mo single atoms anchored on activated carbon (Mo-SAs/AC) by the formed Mo-Ox bonds. The result was published on Chemical Communications.

According to the researchers, this new oxygen-coordinated molybdenum single atom catalyst was proved efficient to electrosynthesis of ammonia. The O-coordinated environment in this study, different from N-coordinated environment reported before, provided the sites to anchor Mo single atoms and form Mo-Ox sites, which could be used as the active centers for the adsorption and activation of N2, resulting in high nitrogen reduction reaction (NRR) activity.

"We have been curious about the key to the high NRR catalytic activity," said GENG Jing, first author of the study, "then we found the Mo-Ox site in the catalyst."

In this research, the surface-rich oxygen functional groups of pre-treated activated carbon played an important role in capturing the Mo precursor, forming Mo-O coordination to anchor Mo atoms as the catalytic active sites.

As a result, in Na2SO4 electrolyte, the Mo-SAs/AC can produce ammonia and attain a faradaic efficiency with high stability and good durability.

This work would be very helpful for designing and developing oxygen-coordinated single atom NRR electrocatalysts for high efficiency electrosynthesis of ammonia.

This work was financially supported by the National Key R&D Program of China, the Natural Science Foundation of China, the China Postdoctoral Science Foundation, and the HFIPS Director's Fund.

A new software tool developed by Earlham Institute researchers will help bioinformaticians improve the quality and accuracy of their biological data, and avoid mis-assemblies. The fast, lightweight, user-friendly tool visualises genome assemblies and gene alignments from the latest next generation sequencing technologies.

Called Alvis, the new visualisation tool examines mappings between DNA sequence data and reference genome databases. This allows bioinformaticians to more easily analyse their data generated from common genomics tasks and formats by producing efficient, ready-made vector images.

First author and post-doctoral scientist at the Earlham Institute Dr Samuel Martin in the Leggett Group, said: "Typically, alignment tools output plain text files containing lists of alignment data. This is great for computer parsing and for being incorporated into a pipeline, but it can be difficult to interpret by humans.

"Visualisation of alignment data can help us to understand the problem at hand. As a new technology, several new alignment formats have been implemented by new tools that are specific to nanopore sequencing technology.

"We found that existing visualisation tools were not able to interpret these formats; Alvis can be used with all common alignment formats, and is easily extensible for future ones."

A key feature of the new command line tool is its unique ability to automatically highlight chimeric sequences - weak links in the DNA chain. This is where two sequences - from different parts of a genome or different species - are linked together by mistake to make one, affecting the data's accuracy.

Chimera sequences can be problematic for bioinformaticians when identifying specific DNA. The chimera formation can physically happen to the DNA molecules during either sequencing library preparation, during the sequencing process on some platforms, and by assembly tools when trying to piece together a genome.

During the development of the tool, the team compared genome assemblies with and without using Alvis chimera detection. The vector image (example_contigalignment.pdf) produced shows an example output, where the intuitive tool tracks all reads it recognises as chimeras.

"Although chimeric sequences don't make up a large proportion of samples, they can have a significant effect, so we have to be careful that we have identified them during analysis," said Dr Martin.

"In the Alvis diagram example of chimera data, each rectangle across the page represents a read, and the coloured blocks inside them represent alignments. Most chimeras are easy to see because their alignments are different colours, meaning they map to different genomes. Others are more subtle because both alignments are to the same genome, but different regions."

The Alvis tool can pinpoint visualisation of only chimeric sequences for further inspection, and output numerical data describing the chimeras. This demonstrates that by applying the tool and then bioinformatically splitting the chimeras, the quality of the assemblies is significantly improved.

Accessed over 600 times since being made available at the beginning of March this year, Dr Martin, adds: "We hope that Alvis continues to be useful to other researchers working with, for example, nanopore sequencing; improving their understanding of their data by visualising alignments,''.

"Alignments are so fundamental to bioinformatics that it could be of use to anyone working with long read sequencing data, as well as alignments generated by sequencing data from short-read platforms. The diagrams that Alvis generates can be easily exported to directly use in publications, demonstrated in our study already."

The paper "Alvis: a tool for contig and read ALignment VISualisation and chimera detection" is published in BMC Bioinformatics.

One day in the near future dyes in electric motors might indicate when cable insulation is becoming brittle and the motor needs replacing. Scientists at Martin Luther University Halle-Wittenberg (MLU), together with ELANTAS, a division of the specialty chemicals group ALTANA, have developed a new process that enables the dyes to be directly integrated into the insulation. By changing colour, they reveal how much the insulating resin layer around the copper wires in the motor has degraded. The results were published in the journal "Advanced Materials".

Modern combustion engines have long had detectors that recognise, for example, when an oil change is needed, saving unnecessary inspections. Electric motors also show signs of wear. Inside, they are usually made up of tightly wound copper wires - and these in turn are coated with an insulating resin. "This insulation changes over time. It becomes brittle as it degrades dues to heat and chemical processes," explains Professor Wolfgang Binder from the Institute of Chemistry at MLU. However, it is not possible to tell from the outside whether the insulation around the wires inside is still intact or whether the entire motor needs to be replaced.

The scientists from MLU were tasked with finding a solution to this problem on behalf of the ELANTAS division of ALTANA, which produces special resin systems for such insulation. "Until now, developers have focused on the degree to which material degrades under specific conditions," explains Alexander Funtan, a chemist at MLU. Recommendations were then made as to how long it would take before a replacement would be necessary. However, the actual wear depends on the conditions under which it is used, most particularly temperature. Funtan therefore developed a test rig which he used to analyse four different resin systems over several months to determine which degradation products form at different temperatures.

He discovered that the four resin systems consistently released a specific alcohol under the different temperature conditions. "We then worked closely with the researchers and developers at ELANTAS to find a sensor molecule for this alcohol," he says. In other words, a substance that is easily detectable and whose properties change when the alcohol binds to it. The sensor molecule must also withstand high temperatures and normal production processes. Another requirement was that it did not change the insulation's electrochemical properties. The choice fell on a dye that normally glows reddish orange under UV light; but when alcohol binds to it, the colour spectrum shifts to a light green.

The different colour spectra could then be analysed using special devices that could be installed directly in the engine. "This way, you can see if a replacement is necessary without having to open up the engine," says Binder. This will hopefully avoid unnecessary motor replacements in the future. The new insulation could be used in the motors of electric vehicles as well as in machines and other equipment. "These results reveal what can be achieved by combining basic university research with commercial application know-how," says Dr Simon Rost, head of research & development at ELANTAS in Hamburg. "In the future, this will enable us to provide added value to our customers and further contribute to sustainable development."

ELANTAS filed a patent for the new process at the beginning of the year. The research was financed by the specialty chemicals group ALTANA and also funded by the EU's BAT4EVER project as part of the "Horizon 2020" programme.

Recently, Prof. WANG Junfeng from the High Magnetic Field Laboratory of the Hefei Institutes of Physical Science (HFIPS), together with international scholars, developed a novel circular permutated light-oxygen-voltage 2 (LOV2) to expand the repertoire of genetically encoded photoswitches, which will accelerate the design of novel optogenetic devices. The result was published in Nature Chemical Biology.

LOV2 domain is a blue light-sensitive photoswitch. In a typical LOV2-based optogenetic device, an effector domain is fused after the C-terminal Jα helix of LOV2, intending to cage the effector via steric hindrance in the dark. On photostimulation, light-triggered unfolding of the Jα helix exposes the effector domain to restore its function. Crafting a LOV2-based photoswitchable protein often takes tremendous engineering efforts to optimize each component and the connecting linker in between. Therefore, it is desirable to expand the current optogenetic toolbox by creating new modules that simplify these steps.

In this study, the researchers designed cpLOV2 using circular permutation, a robust protein engineering approach previously used to evolve new variants of genetically encoded fluorescent probes and biocatalysts. The nitrogen (N) and carbon (C) termini of cpLOV2 were created at the N-terminus of Jα helix while the old ones were connected by a glycine and serine-rich linker. Therefore, the effector could be fused before the N-terminal Jα of cpLOV2 in addition to the C-terminus in LOV2.

Using high resolution NMR spectroscopy and other techniques, the researchers demonstrated that the structural integrity and function of light-induced Jα dissociation of cpLOV2 are well maintained. cpLOV2 was also well worked in LOVTRAP and improved light-induced dimer (iLid), both are LOV2 based optical heterodimerization systems.

cpLOV2 provided more choices for optogenetic application developments. The researchers generated a series of hybrids by fusing LOV2 or cpLOV2 with different Ca2+ channel-activating and autoinhibition fragments derived from stromal interaction molecule 1, and found several novel cpLOV2 based optical actuators to gate ORAI1 Ca2+ channel, therefore they demonstrated that cpLOV2 could afford new caging surfaces to overcome limitations associated with wild type LOV2.

For effectors required a free N terminus to execute its full function, cpLOV2 is a better choice. A key protein involved in necroptosis, mixed lineage kinase domain-like (MLKL) protein, was the successful caged and uncaged in cpLOV2-MLKL but not MLKL-LOV2 to optical control of cell suicides.

Chimeric antigen receptor (CAR) T cell therapy has emerged as a promising immunotherapeutic approach. However, the uncontrollable CAR T cell activity during therapy would cause severe side-effects e.g. cytokine release syndrome in some patients. Researchers designed cpLOV2 based optical heterodimerization systems (cpLID), and constructed photo-tunable split CAR (optoCAR). The therapeutic optoCAR T cells can be specifically activated by CD19 tumor antigen and blue light, and then proliferate to kill CD19+ Raji lymphoma cells.

In mouse model implanted with CD19+ Raji cells, researchers used upconversion nanoparticles (UCNPs) to convert the high tissue penetrative near-infrared light to blue light and activate the injected optoCAR T cells and achieved highly effective therapy of lymphoma tumor. OptoCAR T cells developed in this study permit the spatiotemporal and reversible control of T cell activities and cytokine production.

These encouraging results suggest optoCAR T cells could mitigate potential side effects without losing therapeutic efficacy. In the future, they plan to try "optogenetic immunotherapy" to treat different types of cancer.

A research group at the University of Córdoba studied the molecular properties of the holm oak (Quercus ilex) in search of trees that are more resistant to drought and root rot.

One of the biggest problems affecting holm oaks is drought. The holm oak (Quercus ilex) boasts a high natural adaptability and resistance to inclement weather conditions in dry environments with high temperatures. However, drought is one of the main causes of mortality in holm oak plantations, with "drought stress" also an important factor contributing to root rot.

This is a multifactorial syndrome that causes the decay and death of holm oaks, consisting of a combination of stress due to drought, high temperatures, and attacks by soil pathogens (mainly Phytophthora cinnamomi), a situation that will tend to worsen in a scenario of climate change. However, not all holm oaks are equally affected. Some exhibit greater resistance and tolerance to these stresses, and are called "elite" specimens, thus being the most interesting to study.

The research group AGR-164 "Biochemistry, Proteomics and Biology of Plant and Agroforestry Systems" at the University of Cordoba carried out a study that will make it possible to identify the trees with the best chance of surviving under the most adverse circumstances.

This study, coordinated by Dr. María Ángeles Castillejo, together with Professor Jesús V. Jorrín-Novo and Dr. Lola Rey, focused on investigating this species, about which very little is known at the molecular level, despite the fact that, according to the Castillejo: "the holm oak is the most important and representative species of the Andalusian forest ecosystem, la dehesa, and of the Mediterranean forest". Working with forest species entails a great effort and is a challenge due to their high biological variability and long life cycles, she explained. To this it must be added that "currently there is not yet a sequenced holm oak genome, although we are working on it and hope to have it shortly. This will mean, without a doubt, a great advance in the molecular study of this species", Castillejo explained.

The importance of studying the oak lies in its ecological, environmental and economic value. In fact, in addition to serving as sustenance for pigs, in recent years there has been a renewed interest in the human consumption of acorns, "due to its beneficial nutritional and pharmacological properties, about which little is still known", according to Castillejo.

Therefore, the molecular study of specimens exhibiting a high tolerance to drought has great potential. Thus, the objective of this research project was to identify trees that are more tolerant of drought through the study of their proteome proteins in order to determine those that may be involved in said tolerance.

For this, four populations from different parts of Andalusia were chosen, and a drought stress experiment was carried out with their seedlings. Physiological studies (such as the measurement of leaf fluorescence) were carried out to determine the drop in photosynthesis, and, thus, select two sampling times for the subsequent molecular analysis. Those proteins that increased in response to the drought, which happened in at least two of the populations studied, were selected for a second analysis.

This dual strategy for the quantification of proteins and peptides (a type of molecule) made it possible to select those most stable over time, which may be involved in drought tolerance, such that they could be used as possible molecular markers. "Those trees whose genome is expressing the greatest number or quantity of these proteins are probably more tolerant to drought", added the researcher.

Thus, it was possible to propose a list of possible markers that will be used by growers to include them in their selection of specimens and reforestation programs to repopulate areas affected by drought.

Autism spectrum disorder is a neurodevelopmental condition involving impaired social abilities, and this makes it a fascinating subject for neuroscientists like Prof. Teiichi Furuichi of the Tokyo University of Science who study the neuroscience of social behavior. Prof. Furuichi and his colleagues have previously worked on developing mouse models of autism to unravel the condition's neurochemical mechanisms, and in a paper recently published in the prestigious Journal of Neuroscience, they provide evidence that a genetic mutation associated with autism can impair the release of a peptide called oxytocin that plays an important role in regulating social behavior. This finding promises to broaden our understanding of the neurobiology of social behavior.

The gene that Prof. Furuichi's team chose to study is Caps2, which encodes a protein called Ca2+-dependent activator protein for secretion 2 (CAPS2) that regulates the release of brain chemicals (or "neurotransmitters"). Previous studies have shown that CAPS2 deficiencies in mice cause behavioral impairments such as reduced sociality, increased anxiety, and disrupted circadian rhythms. Furthermore, a study of Japanese patients with autism spectrum disorder revealed that some of them had Caps2 mutations that adversely affect the CAPS2 protein's functions. Prof. Furuichi and his colleagues had previously discovered that the CAPS2 protein is expressed in neurons in the hypothalamus and pituitary gland that release the neuropeptide oxytocin. This information formed the basis of their recent study. As Prof. Furuichi explains, "We hypothesized that CAPS2 deficiencies in mice should alter oxytocin release, which should in turn result in impaired social behavior."

To test this hypothesis, researchers Shuhei Fujima, Graduate Student at Tokyo University of Science; Yoshitake Sano, Junior Associate Professor at Tokyo University of Science; Yo Shinoda, Associate Professor at Tokyo University of Pharmacy and Life Sciences; Tetsushi Sadakata, Associate Professor in Gunma University; Manabu Abe, Associate Professor at Niigata University; and Kenji Sakimura, a Fellow of Niigata University, among others, led by Prof. Furuichi conducted a series of experiments involving mice that carried genetic alterations that prevented them from expressing the CAPS2 protein. These mice had lower-than-normal oxytocin levels in their blood but higher-than-normal oxytocin levels in the hypothalamus and pituitary gland. The researchers interpreted this finding as evidence that CAPS2 deficiencies impede the normal release of oxytocin from these brain regions into the bloodstream.

Unsurprisingly, the reduced bloodstream levels of oxytocin had clear behavioral effects. When placed inside a rectangular box, the oxytocin neuron-specific CAPS2-deficient mice were unwilling to spend much time in the center of the box, and the researchers interpreted this as evidence of increased anxiety about the risk of a predator attacking them. The CAPS2-deficient mice also exhibited diminished willingness to engage in social interactions when introduced to unfamiliar mice. Interestingly, spraying an oxytocin solution into the noses of the CAPS2-deficient mice acted to restore their willingness to socially interact with unfamiliar mice.

Based on these findings, Prof. Furuichi and his colleagues conclude that the CAPS2 protein plays a critical role in facilitating the release of peripheral oxytocin into the bloodstream. They similarly suggest that CAPS2 is also involved in the release of central oxytocin into the brain regions relating to the control of sociality. Given the key role that oxytocin plays in regulating social behaviors, this could help to explain how mutations in the Caps2 gene could lead to atypical patterns of social behavior in persons with autism spectrum disorder. When asked about the social significance of his team's work, Prof. Furuichi remarks, "We believe that this research, although basic, is an important achievement that will contribute to the development of tools for the early molecular diagnosis and effective treatment of autism spectrum disorder."

Given the relatively high prevalence of autism and how extremely disabling severe cases can be, the development of effective treatments would have major benefits for people with autism and the society as a whole.

In the field of international business research, lobbying is considered a legitimate and legal political action conducted in a developed economy. Bribery, on the other hand, is seen as an outright corrupt practice in an emerging economy.

In a study published in the March issue of the journal Business & Society, a researcher from The University of Texas at Dallas examined the gray area between lobbying and bribery among multinational companies, especially in countries where lobbying is not regulated strongly or institutional development is insufficient.

The analysis found that firms based in developed countries, as opposed to developing countries or transition economies, are more likely to influence the institutional environment of host countries through lobbying, even when bribery is expected to be a more prevalent way of doing business in many of these countries.

"We wanted to address this and call for more attention to the issue of lobbying as an equally important issue as bribery in firm activities to influence the institutional environment in the international business context. For example, addressing institutional constraints overseas by shaping regulatory and policy environments in a more favorable way can increase performance benefits," said study author Dr. Seung-Hyun Lee, professor of organizations, strategy and international management in the Naveen Jindal School of Management.

"Moreover, while bribery has been largely seen as what firms from transition economies do, there has been little discussion of the lobbying attempts that firms from more developed economies are doing. We wanted to shed light on this, too."

In the study, Lee and co-author Dr. Jisun Yu of Concordia University in Montreal investigated what determines a multinational enterprise's propensity to engage in lobbying and bribery in countries where the overall institutional development for market exchanges is insufficient and overall country governance is relatively weak.

A transition economy is one that endeavors to change from a planned economy to a market economy. Examples include China and Vietnam. For the study, the researchers focused on the transition economies of central and eastern European countries and members of the Commonwealth of Independent States, a regional organization of countries from the former Soviet Union.

"While transition economies are full of uncertainty due to structural transitions and the uneven development of adequate institutions, these very characteristics are also a source of opportunities, such as low-cost production, highly educated labor forces and easy access to the European market," Lee said.

Using data from the Business Environment and Enterprise Performance Survey conducted in transition economy countries by the World Bank, the researchers aimed to further discussions concerning the ethical and social implications of corporate activities conducted to influence institutions.

Their analysis found that multinational enterprises based in a country with a strong governance system are less involved in bribery but have a higher tendency to lobby their hosts in transition-economy countries. The researchers found that this tendency holds true even when these enterprises rely on the host country's local market for much of their sales.

The study also found that firms from a home country with more developed governance also attempt to change the laws to a greater extent in host countries with weaker institutional development.

"Multinational enterprises behave consistently in host countries and tend to stick to the way business was done in their domestic markets, even when dependence on local sales in host countries increases," he said. "It is a good thing to find that multinational enterprises from countries with a stronger governance system are less likely to bribe in transition economies, compared to their counterparts with weaker governance."

Lee said it is important for policymakers to understand that home country governance can be an effective mechanism in controlling a multinational enterprise's illegal political activities, even outside its home boundaries.

"When it comes to host countries, governments there may want to make sure that lobbying is effectively governed and bribery is curbed to incentivize multinational enterprises hailing from stronger governance systems to invest in their countries," he said.

Policymakers might also consider strengthening their country's governance system as a way of reducing their multinational enterprises' unwanted involvement in corruption overseas, Lee said.

Counselling sessions improve long term mental health in primary-school aged children, according to a new study. The research has implications for reversing declining mental health in young people in a COVID-19 era.

A team from the University of Exeter and the University of Cambridge worked in partnership with Place2Be to assess the longer-term impact of its school-based service.

The study assessed the impact of Place2Be's programme, in which trained counsellors operated in 171 schools nationwide in the academic year 2015/16. Under the scheme, children could self-refer to the counsellors for any reason, or be referred by parents or teachers.

Researchers analysed data on 740 children who took up one-to-one counselling, collected before the counselling started, after the sessions finished, and approximately one year after this. The children did not have to have mental health disorders to take up the counselling, however a comparison with children who were being seen by NHS mental health services indicated that they had similar levels of poor mental health.

The research, published in European Child and Adolescent Psychiatry, used data from the Strengths and Difficulties Questionnaire (SDQ) completed by teachers and parents. One year later, this data showed that the children who spoke to counsellors had considerably better mental health than a comparative group of children who had poor mental health yet had not seen a counsellor.

Lead author Dr Katie Finning, of the University of Exeter, said: "We know that children's mental health is deteriorating, while access to child and adolescent mental health services is decreasing. Our research indicates that children who have access to a counsellor at primary school see benefits to their mental health over the longer term compared to children who don't. School-based counselling could help address the urgent need to support children's mental health, and could help reduce pressure on oversubscribed child mental health services."

Previously published research has concluded that Place2Be's counselling intervention has economic benefits resulting from higher employment output and lower spending on public services, amounting to over £5,700 per child. However, this amount was based on the intervention having short-term benefits that faded more quickly than the new research suggests. So the savings per child are likely to be an under-estimate, given the new finding that benefits are longer-term.

Professor Tamsin Ford, from the University of Cambridge, who supervised the research, said: "We've previously found that children's mental health has worsened during the pandemic. We need to prioritise the provision of evidence-based mental health support in schools. Early intervention at this young age, before mental health problems become entrenched in adolescence and young adulthood, may help to prevent the long-term impacts of childhood mental health problems."

Catherine Roche, Chief Executive of Place2Be, said: "This study reinforces our evidence that high quality school-based mental health support not only helps children to get the most out of their education, but can also prevent problems from growing over time - impacting children's life chances. Schools are on the frontline and have the opportunity to make mental health services easily accessible for families. But school leaders and teachers cannot do this alone, they need quality training, easy referral routes and timely access to specialist mental health services - only when all parts of the system work together will children get the help they deserve."

HAMILTON, ON May 18, 2021 -- Five years after the disastrous wildfire in Fort McMurray, Alberta, researchers are warning that the complex role of peatlands, a factor critical to projecting the risk and behaviour of future fires, is missing from the forecasting model.

The Fort McMurray fire burned out of control from May 1 to July 5, 2016, though it continued to smoulder until it was finally declared extinguished Aug. 2, 2017.

Peat deposits - which are prevalent across Canada, especially in Alberta - are complex threats that can complicate and magnify the risk of severe, long-lasting fires and heavy smoke, but they are not yet part of the standard assessment tools that fire managers use.

It's a critical gap that should be addressed urgently, say the authors of a new paper published today in the International Journal of Wildland Fire, who have completed the first scientific assessment of peatland smouldering fire potential.

"Our understanding of this risk is advancing quickly because it needs to. Year on year, wildfires are becoming more severe and having greater impact," says researcher Sophie Wilkinson, lead author of the paper. "We need tools to understand this at every level of management and governance."

Wilkinson, a post-doctoral research fellow in McMaster's School of Earth, Environment and Society, authored the paper with McMaster colleagues Professor James Michael Waddington and Alex Furukawa, and Professor Mike Wotton of the University of Toronto.

The team looked most closely at peat deposits that are home to black spruce trees. The trees can burn quickly, throwing flaming embers into the air and across the landscape, while the peat, once lit, can smoulder for months and even move underground before re-emerging.

The compacted layers of dead Sphagnum moss and other vegetation, steeped in groundwater and topped by living moss and sometimes black spruce, are huge vaults of carbon.

Once viewed as benign wetland firebreaks, these complex ecosystems are not necessarily resistant to fire and can extend and accelerate wildfires. When climate change and human activity accelerate the drying of such wetlands, stored peat becomes even more dangerous fuel for smoky, stubborn and potentially devastating fires.

"I think the Fort McMurray fire really highlighted the lack of understanding of ecosystems in that area and the interplay between them," Wilkinson says. "It's concerning from a public health and safety perspective, and in terms of its feedback with climate change."

The researchers were able to perform a detailed study in Alberta because peatlands there are more thoroughly mapped, but they believe similar risks exist throughout the boreal peatlands of Canada.

The risk of peat fire is shaped by the type and depth of a peat deposit, the geological structure beneath it, and the presence of trees on its surface, all influenced by rain, wind and temperature - collectively known as "fire weather".

Sometimes fire moves swiftly over peatlands, while other times it digs in. Often, the researchers find, the potential for the worst peat fires is in the smallest, shallowest deposits, which are common in the more populated southern areas of the Boreal Plains.

"It's challenging because there are so many counterintuitive elements at play. These are wetlands that are burning," Wilkinson says.

"A good understanding of how fire is likely to behave in relation to these variables is not yet available to fire managers. I think awareness is growing, and peat fires are getting onto the radar of the public and policymakers more, but the actual scale of the carbon stored in peatlands and the potential to release it through fire is not well understood by the public."