Culture

A new technique established by a team of researchers from the University of Cambridge and the University of Massachusetts reveals the fundamental physics of how a polymer such as DNA threads through holes 10,000 times smaller than the width of a human hair.

Polymers are long, chain-like molecules which are everywhere in biology. DNA and RNA are polymers formed by many consecutive copies of nucleotides coupled together. When being transported within or between cells, these biological polymers must pass through nanometre-sized holes called "nanopores".

This process also underlies a rapidly developing method for analysing and sequencing DNA called nanopore sensing.

The study, published in the journal Nature Physics, shows how the Cavendish-led team developed a new LEGO-like technique for assembling DNA molecules that have protruding bumps at specific locations along their length. By passing these DNA molecules through a nanopore and analysing simultaneous changes in the pattern of ion flow, the researchers determined with great precision how the speed of the DNA changes as it moves through.

The experimental results revealed a two-step process where the DNA speed initially slows down before accelerating close to the end of the translocation. Simulations also demonstrated this two-stage process and helped to reveal that the underlying physics of the process is determined by changing friction between the DNA and surrounding fluid.

"Our method for assembling LEGO-like molecular DNA rulers has given new insight into the process of threading polymers through incredibly small holes just a few nanometres in size," explained Senior author Dr Nicholas Bell from Cambridge's Cavendish Laboratory. "The combination of both experiments and simulations have revealed a comprehensive picture of the underlying physics of this process and will aid the development of nanopore-based biosensors. It is very exciting that we can now measure and understand these molecular processes in such minute detail."

"These results will help improve the accuracy of nanopore sensors in their various applications, for instance localising specific sequences on DNA with nanometer accuracy or detecting diseases early with target RNA detection," said lead author Kaikai Chen.

"The superior resolution in analysing molecules passing through nanopores will allow for low-error decoding of digital information stored on DNA. We are exploring and improving the utility of nanopore sensors for these applications."

Researchers at the University of Leicester have developed a new method to recycle electric vehicle batteries using a ground-breaking new approach that many will have experienced in the dentist's chair.

The Faraday Institution project on the recycling of lithium-ion batteries (ReLiB) led by Professor Andy Abbott at the University of Leicester used a new method, involving ultrasonic waves, to solve a critical challenge: how to separate out valuable materials from electrodes so that the materials can be fully recovered from batteries at the end of their life.

Current recycling methods for lithium-ion battery recycling typically feed end-of-life batteries into a shredder or high-temperature reactor. A complex set of physical and chemical processes are subsequently needed to produce useable materials. These recycling routes are energy intensive and inefficient.

If an alternate approach is taken and end-of-life batteries are disassembled rather than shredded, there is the potential to recover more material, in a purer state. The disassembly of lithium-ion batteries has been shown to recover a high yield (around 80% of the original material) in a purer state than was possible using shredded material.

The stumbling block - of how to remove and separate critical materials (such as lithium, nickel, manganese and cobalt) from used batteries in a fast, economical and environmentally-friendly way - can now be avoided thanks to the new approach which adapts technology currently in widespread use in the food preparation industry.

The ultrasonic delamination technique effectively blasts the active materials required from the electrodes leaving virgin aluminium or copper. The process proved highly effective in removing graphite and lithium nickel manganese cobalt oxides, commonly known as NMC.

The research has been published in Green Chemistry and the research team led by Professor Abbott have applied for a patent for the technique.

Professor Abbott said:

"This novel procedure is 100 times quicker and greener than conventional battery recycling techniques and leads to a higher purity of recovered materials.

"It essentially works in the same way as a dentist's ultrasonic descaler, breaking down adhesive bonds between the coating layer and the substrate.

"It is likely that the initial use of this technology will feed recycled materials straight back into the battery production line. This is a real step change moment in battery recycling."

Professor Pam Thomas, CEO, The Faraday Institution commented:

"For the full value of battery technologies to be captured for the UK, we must focus on the entire life cycle -- from the mining of critical materials to battery manufacture to recycling -- to create a circular economy that is both sustainable for the planet and profitable for industry."

Faraday Institution researchers have been focused on the life cycle of the battery - from their first production to their re-use in secondary applications to their eventual recycling, to ensure that the environmental and economic benefits from Electric Vehicle batteries are fully realised.

The research team are in initial discussions with several battery manufacturers and recycling companies to place a technology demonstrator at an industrial site in 2021, with a longer-term aim to license the technology.

The research team has further tested the technology on the four most common battery types and found that it performs with the same efficiency in each case.

Mineral resources from Chile are of great importance to Germany. According to statistics from the World Bank, thousands of tons of valuable minerals are imported from the South American country every year, including raw materials for lithium-ion batteries. But their extraction causes ecological and social problems: "The use of the limited freshwater resources in northern Chile for mining regularly fuels conflicts with the local population," says Professor Thomas Kohl from KIT's Institute of Applied Geosciences (AGW). "Northern Chile is one of the driest regions on earth, but has extensive geothermal resources. With a novel type of plant, it is not only possible to generate electricity in a climate-friendly way, but also to extract drinking water and even mineral resources at the same time." The AGW team of BrineMine, a German-Chilean research project, is developing the necessary strategies and technologies.

AGW has a long history of cooperation in the field of geothermal research in Chile. Its main partner is the Centro de Excelencia en Geotermia de Los Andes (CEGA). "BrineMine demonstrates how well the cooperation between Chilean and German institutions works," says Professor Diego Morata, director of CEGA. "Sustainable development, achieved by the combination of geothermal and green mining, can benefit Europe and the Andean region alike."

First Demonstration Plant on the Upper Rhine Graben

Part of the transdisciplinary research initiative is dedicated to the geochemical and geothermal potential of thermal wells in Chile in order to identify suitable sites. A data survey is being conducted to determine the raw materials potential with a focus on the thermal fields of the Atacama Desert. In addition, the Fraunhofer Institute for Solar Energy Systems (ISE) takes part in the BrineMine project by developing the plant technology for later industrial use. It is based on a novel process chain: First, heat from the geothermal brine is used for energy recovery. The cooled liquid, which has a relatively low concentration, is then pre-concentrated by reverse osmosis; at the same time, drinking water is obtained. The brine concentrate is then further concentrated by membrane distillation until it is saturated. "The thermal energy required for the entire process can be covered directly from the excess heat of the power plant process," explains project manager Dr. Joachim Koschikowski from ISE. "We have already set up a demonstration plant in a geothermal power plant in the Upper Rhine Graben and successfully integrated key components into ongoing power plant operations."

Optimization of Processes for Raw Material Mining

Most of the process steps are based on proven methods, but they have never been combined in this way. Detailed research is required, because, for example, both concentration and cooling increase the risk of silicate deposits. "Conventional strategies for silicate removal would greatly impair the extraction of the resources. Without water treatment, the technical plant components would be damaged," explains Valentin Goldberg from KIT's AGW. The researchers found a viable solution by changing the pH value of the brine and adding divalent cations (e.g. calcium or magnesium). "Our silicate removal method is fast and effective. Most importantly, it has no negative impact on raw material extraction," Goldberg says. The researchers describe this new approach in the Geothermics journal.

Before the first plants can be installed in Chile, further details about the process need to be clarified. In addition, specific models for economic operation are also being developed.

When positioned strategically, garment seams sewn with conductive yarn can be used to accurately track body motion, according to computer scientists at the University of Bath in the UK. Best of all, these charged seams are able to respond to subtle movements that aren't picked up by popular fitness trackers, such as watches and wristbands.

In a new study, the Bath researchers found that clothing made with conductive seams can be analysed to identify the wearer's movements.

PhD student Olivia Ruston, who presented the work at the ACM Designing Interactive Systems conference this month, said: "There are lots of potential applications for conductive yarn in any activity where you want to identify and improve the quality of a person's movement. This could be very helpful in physiotherapy, rehabilitation, and sports performance."

Groups of scientists have been creating flexible, textile sensors for garments for some time, but the Bath project is the first where researchers have experimented with the location and concentration of conductive seams. They found that where seams are placed on a garment, and the number of seams that are added, are important considerations in the design of a movement-tracking smart garment.

Ms Ruston said: "There's great potential to exploit the wearing of clothing and tech - a lot of people are experimenting with e-textiles, but we don't have a coherent understanding between technologists and fashion designers, and we need to link these groups up so we can come up with the best ideas for embedding tech into clothing."

The yarn used by Ms Ruston and her team comprises a conductive core that is a hybrid metal-polymer resistive material intended for stretch and pressure sensing. Once incorporated into a garment's seam, it is activated at low voltages. The resistance fluctuates as body movement varies the tension across the seams.

In the study, the seams were connected to a microcontroller, and then a computer, where the voltage signal was recorded.

Professor Mike Fraser, co-author and head of Computer Science, said: "Our work provides implications for sensing-driven clothing design. As opportunities for novel clothing functionality emerge, we believe intelligent seam placement will play a key role in influencing design and manufacturing processes. Ultimately, this could influence what is considered fashionable."

Mice are an important animal model of human vision due to the powerful genetic tools available in this species. However, mouse vision was thought to be different to that of humans because humans have a region of the retina specialized for fine details called the 'fovea' whereas mice do not. Researchers from the Netherlands Institute of Neuroscience (NIN) have shown that the visual cortex of mice does contain a region of enhanced visual sensitivity dubbed the 'focea', making the mouse a better model of human vision than previously expected. The findings were published in Nature Communications on the 29th June.

A specialization for high resolution vision

The fovea is a region in the human retina in which the light-sensitive cells are more closely packed together yielding higher resolution vision. It is used for reading and recognizing faces. Humans move their eyes three times per second to point the fovea at interesting parts of the world. Mice do not have this specialization and it was thought that they have no reason to move their eyes to 'scan the world' in more detail.

While studying how the retina of the mouse was mapped in cortical regions of the brain, the researchers found that the map of visual space in the cortex has a better visual resolution at a location that represents a region directly in front of and slightly above the mouse in space. They named this cortical location the 'focea' as it is reminiscent of the fovea of humans.

A better organized map of space.

To determine the source of the better resolution the researchers measured the responses from individual brain cells using electrodes. The cells at the focea did not appear to the differ from other cells. "Initially we were puzzled" explains Matthew Self, lead researcher on the project, "we were seeing a very clear focea in the map, but nothing when we measured the data from single-neurons. We realized that the focea could originate from regions of the cortex where the maps are better organized across cells".

To study this, the researchers measured maps of space across thousands of cells using a two-photon microscope. The results confirmed their hypothesis; maps of space in the focea were well-organized with neighboring cells responding to neighboring parts of space. In contrast, the maps outside the focea were more scattered. The results suggested that mice might have better vision in the focea than elsewhere.

The focea in natural behaviors

The fact that mice have a focea could mean that they also move their eyes to point their focea at interesting parts of world, analogous to the human fovea. The findings have important consequences for the use of mice as a model of human vision. Dr Self stated: "The fact that mice have a focea opens up the possibility of understanding the neural circuits underlying high-detail vision and studying the neural basis of attention and eye-movements in this species".

Lithia, Florida -- June 29, 2021 -- Surgical resident training has traditionally occurred in a master-apprentice-type relationship, with graduated responsibilities until trainees are expected to perform procedures on their own. Given recent changes in the health care system, including reduced operating room time, increased difficulty of procedures and working hour restrictions, there is less time for residents to learn using traditional methods.

Researchers from the University of Manitoba and the Pan Am Clinic recently published a paper in the journal Arthroscopy, Sports Medicine, and Rehabilitation that looked at the effectiveness of a mixed reality simulator for the training of arthroscopy novices. Following this study, the residency program has made it a requirement in the curriculum that residents in the sports rotation complete the self-learning modules.

Dr. Samuel Larrivée, one of the study's authors, stated that "sports surgeons at our institution noted anecdotally that junior residents had difficulty reaching competency in arthroscopic skills by the end of their three-month rotation, and were not as prepared when starting their senior rotation. There was a need to increase training opportunities outside of the operating room in order to prepare our residents for independent practice."

Prior to obtaining the ArthroS™ simulator from VirtaMed, the University of Manitoba Orthopedic Surgery program occasionally used simulation such as benchtop dry simulators, cadavers and an older generation simulator with active haptics. These were mostly used to complement academic teaching sessions in small groups with some success, and available for use by residents as needed. However, due to the low fidelity and difficult setup, few residents took up the opportunity.

Medical student engagement with the ArthroS simulator was different. Alisha Beaudoin, a co-author and medical student, attested to her experience using the ArthroS simulator in her early training. "I found this training to be very helpful during my surgery rotation. Many of my preceptors were impressed by my superior arthroscopic and laparoscopic skills. This training may allow students with an interest in surgery to be more prepared."

Recently, many Canadian universities have moved to competency-based curriculums where residents must demonstrate competency prior to moving to the next defined practice level. The study noted that this is similar to the training available on ArthroS and that "a user enrolled in the mentoring program is progressed through various levels of training by meeting training targets, essentially providing a proficiency-based progression."

This paper is the first in what the authors hope is a larger body of work on validating arthroscopy simulators for resident training. There are currently plans to repeat similar studies with the other modules (hip, shoulder, and ankle), with larger sample sizes, and at different levels of training.

The Study

Study participants were divided into three groups: simulator training only, mentor-based training, and a control. At the end of four weeks, surgical performance improved among both traditional and simulator-based training groups. The study concluded that "simulator training may provide enhanced skills to improve patient safety overall, as residents may become more skilled earlier in their training, leaving more time for the mentor to teach more advanced skills." Beaudoin further explains: "I believe that simulation training should be introduced into the standardized curriculum because I believe it offers a safe space to hone your skills and improve in a stress-free environment."

Based on the study results, residents are now required to complete the self-learning modules as part of training during their sports rotation. Certain modules have been identified at the junior and senior levels. Dr. Larrivée believes this will allow residents to develop their triangulation skills and memorize the steps prior to their first surgery and consolidate their knowledge.

Aerosol generated by playing woodwind and brass instruments is less than that produced when vocalising (speaking and singing) and is no different than a person breathing, new research has found. The findings, published online in the journal Aerosol Science and Technology, could be crucial to developing a roadmap for lifting COVID-19 restrictions in the performing arts, which have been significantly restricted since the start of the pandemic.

The research project, known as PERFORM (ParticulatE Respiratory Matter to InForm Guidance for the Safe Distancing of PerfOrmeRs in a COVID-19 PandeMic), was supported by Public Health England, the Department for Digital, Culture, Media and Sport (DCMS), and UKRI and was carried out by a collaborative team from Imperial College London, University of Bristol, Wexham Park Hospital, Lewisham and Greenwich NHS Trust and Royal Brompton Hospital.

The study looked at the amount of aerosols and droplets generated when playing woodwind and brass instruments compared with breathing and vocalisation (speaking and singing). The work was carried out in an environment with no background aerosol particles to complicate measurement interpretation, with nine musicians playing 13 woodwind and brass instruments.

The research team found aerosol (

Large droplets (>20 μm diameter) were not observed during instrument playing but were observed during singing and coughing. Together the findings indicate that playing woodwind and brass instruments generates less aerosol than vocalising at high volume levels.

Concentrations of aerosol emissions from the musicians during breathing and vocalising were consistent with results from a study carried out last year of a large group of professional singers. No difference was found between the aerosol concentrations generated by professional and amateur performers while breathing or vocalising, suggesting aerosol generation is consistent across amateur and professional singers regardless of vocal training.

Dr Bryan Bzdek, Lecturer in the School of Chemistry at the University of Bristol and corresponding author on the paper, said: "Our study found playing woodwind and brass instruments generates less aerosol than vocalisation, which could have important policy implications in a roadmap to lifting COVID-19 restrictions, as many performing arts activities have been, and continue to be, severely restricted."

Jonathan Reid, Director of Bristol Aerosol Research Centre and Professor of Physical Chemistry in the School of Chemistry at the University of Bristol, added: "This study confirms that the risks of transmission of SARS-CoV-2 are likely elevated during vocalisation at loud volume in poorly ventilated spaces. By comparison, playing wind instruments, like breathing, generates less particles that could carry the virus than speaking or singing."

The death of neurons specialised in the synthesis of dopamine, one of the brain's main neurotransmissors, deteriorates the motor and cognitive capacities of those with Parkinson's disease. The loss of these neurons is related to alpha-synuclein aggregation. Recent studies show that oligomers, the initial aggregates of this protein, are the most pathogenic forms of α-synuclein and are responsible for the spreading of the disease in the brain.

Therefore, one of the more promising approaches in fighting this disorder consists in neutralising these oligomers and, thus, slow down the pathological progression. However, the fact that these aggregates do not present a defined structure and that they are transitory by nature makes it extremely difficult to identify molecules that bind with enough strength as to explore any clinical application.

A scientific collaboration between researchers from the Institute for Biotechnology and Biomedicine (IBB) at the Universitat Autònoma de Barcelona (UAB) and from the Instituto de Biocomputación y Física de Sistemas Complejos (BIFI) of the Universidad de Zaragoza (UniZar) now has been able to identify a human endogenous peptide which strongly and specifically attaches to the α-synuclein oligomers, thus avoiding their aggregation and blocking their neurotoxicity, two processes closely related to the neurodegenerative decline of Parkinson's disease. The identification and study of the peptide, called LL-37, was recently published in Nature Communications.

"LL-37 interacts with the toxic alpha-synuclein oligomers in a selective manner and with a strength superior to that of any peptide previously described, equivalent to the strength exhibited by antibodies. It inhibits aggregation at very low concentrations and protects neuronal cells from being damaged", researchers point out.

They add that, "LL-37 is found naturally in the human organism, both in the brain and in the intestine, organs in which α-synuclein aggregation takes place in Parkinson's disease. This suggests that LL-37's activity might respond to a mechanism developed by the body itself as a means to naturally fight this disease."

Encouraged by this idea, researchers now want to study how its expression can be regulated and if this strategy can become a safe therapy with the potential of influencing the course of the disease. "There is a possibility that a therapy for Parkinson's disease already lies in our interior and that it only needs to be activated correctly", states Salvador Ventura, researcher at the IBB and coordinator of the study.

The identification of LL-37 was conducted under the framework of a research analysing the structure and characteristics of pathogenic oligomers with the aim of neutralising them in a specific manner. The analyses conducted demonstrate that helical peptides with a hydrophobic side and another positively charged side are ideal for this type of activity. The trials allowed researchers to identify three molecules with anti-aggregation activity: in addition to the human molecule, a second peptide present in bacteria and a third artificially made molecule were identified.

In addition to representing a possible therapeutic route for Parkinson's disease and other synuclein pathologies, the molecules identified in the study are promising tools for its diagnosis, given that they discriminate between functional and toxic α-synuclein species.

"Until now there were no molecules capable of selectively and efficiently identifying toxic α-synuclein aggregates; the peptides we present on these issues are unique and, therefore, have great potential as diagnostic and prognostic tools," says study co-coordinator Nunilo Cremades, researcher at BIFI-UniZar.

In the study, over 25,000 human peptides were computationally analysed, and single molecule spectroscopy methods, as well as protein engineering, were applied, in addition to cell cultures in vitro using toxic oligomers.

Participating in the study were researchers from the IBB-UAB and the Department of Biochemistry and Molecular Biology at the UAB Jaime Santos (first author of the article), Irantzu Pallarès and Salvador Ventura (co-coordinators of the study), members of the "Protein Folding and Conformational Diseases" group; and BIFI-UniZar researchers Pablo Gracia (second author of the article) and Nunilo Cremades (co-coordinator of the study, predoctoral researcher and lead researcher, respectively, of the "Amyloid Protein Misfolding and Aggregation" NEUROMOL group from the BIFI-Unizar.

Tuesday, 29 June 2021 - New research has shown that early testing for blood clots in patients who had received the AstraZeneca/Oxford vaccine led to them being treated successfully, highlighting the need for heightened awareness of the risk among doctors.

The work, led by researchers from RCSI University of Medicine and Health Sciences and the National Coagulation Centre at St James's Hospital, is published in the British Journal of Haematology.

Unusual blood clots with low blood platelets have been recognised as a very rare complication of the AstraZeneca vaccine. However, with increased awareness, patients may not have all of these symptoms when they initially present to medical services.

The researchers highlighted four patients who had clotting complications induced by the vaccine (Vaccine Induced Thrombotic Thrombocytopenia, VITT). Based on the current guidance, each patient could have been classified as a low likelihood for this syndrome when they presented to doctors, but due to the increased awareness and clinical vigilance from the medical teams involved, all were sent for testing early, diagnosed and treated successfully.

"The risk of developing a blood clot from the vaccine is still far lower than the risk of developing clots from Covid-19, but it is imperative that clinicians are vigilant in detecting symptoms among vaccinated patients," said Dr Michelle Lavin, the lead author of the paper and researcher at the Irish Centre for Vascular Biology and the RCSI School of Pharmacy and Biomolecular Science.

"Our research has shown that current guidelines lack the sensitivity to detect early cases of vaccine-induced clotting, which could risk missing or delaying diagnoses. As our understanding of this novel condition evolves, heightening our clinical awareness can improve outcomes for patients through early testing and treatment."

This work is part of the Irish COVID-19 Vasculopathy Study (ICVS), supported by a Health Research Board COVID-19 Rapid Response award and also by a philanthropic grant from the 3M Foundation to RCSI University of Medicine and Health Sciences in support of COVID-19 research. The work was carried out in hospitals in both the Republic of Ireland and Northern Ireland.

The LSL60101 compound, a specific ligand of the I2-IR receptors in the brain, could shed light on the development of future strategies against Alzheimer's disease. This is stated in the recent studies by the Research Group on Medicinal Chemistry and Pharmacology of Neurodegenerative Diseases of the University of Barcelona, published in the journals European Journal of Medicinal Chemistry and British Journal Pharmacology. In studies carried out with mice, LSL60101 has improved the cognitive deficit and the biomarkers related to the disease in these animal models.

These studies result from the collaboration of the research teams led by professors Carmen Escolano, from the Faculty of Pharmacy and Food Sciences and the Institute of Biomedicine of the UB (IBUB), and Mercè Pallàs, from the same Faculty and the Institute of Neurosciences (UBNeuro). Framed within a program in the CaixaImpulse program, the studies are also signed by the UB researchers Christian Griñán Ferré, Foteinin Vasilopoulou, Sergio Rodríguez Arévalo and Andrea Bagán. Among the participants are teams of the

Alzheimer's is a neurodegenerative disease without a cure yet. Despite the efforts made by the international scientific community, many initiatives in medical chemistry to find future drugs to treat have failed and it is postulated that this situation could be explained by the selection of unsuitable therapeutic targets. Therefore, it is decisive to tackle the fight against Alzheimer's from perspectives that help to shape new therapeutic targets from the side of the innovation in biomedical research.

The paper published in the European Journal of Medicinal Chemistry describes the synthesis of a new family of compounds with high affinity and selectivity for I2 imidazoline receptors, altered in the brain of patients with Alzheimer's. The synthesis pathway of compounds, which is efficient and affordable, would allow to apply different structural modifications to access a notable range of compounds of pharmaceutical interest.

The new family of I2-IR receptor ligands is formed by compounds with different structural features. In particular, the interaction of a representative compound --LSL60101 or garsevil-- with the I2 imidazoline receptors improves the cognitive deficit in murine models with neurodegeneration and Alzheimer's. This compound, described for the first time in the scientific literature in 1995 as a specific I2-IR receptor ligand, outstands for its properties in preclinical studies of pharmacokinetics, metabolism and toxicity, and presents a high affinity and selectivity regarding these receptors in the human brain.

Nowadays, the function of the I2-IR receptors under physiological conditions is unknown. However, researchers know these are altered in some neurodegenerative diseases such as Alzheimer's or Parkinson's. Moreover, the scientific bibliography features studies with ligands of these receptors as markers of the progress of Alzheimer's disease.

"Apart from fighting the formation of amyloid-beta plaques or neurofibrillary tangles, acting on the neuroinflammation mechanisms could be a suitable therapeutic strategy to stop the progression of such a complex disease like Alzheimer's", notes Professor Carmen Escolano.

LSL60101 versus donepezil: the future of a combined therapy

According to the article in British Journal Pharmacology, the effects of LSL60101 in laboratory animals prove to be mor beneficial than those from donepezil, one of the most commercialized drugs for Alzheimer's treatments.

In the murine models with Alzheimer's, "the new compound created changes in oxidative stress markers and in neuroinflammation makers, one of the main dysfunctions present in most of the neurodegenerative diseases. In particular, LSL60101 reduced the number of amyloid-beta plaques and the levels of this altered protein in the brain of the treated animals. Parallelly, it reduced the phosphorylation of the tau protein, another important biomarker in the progression of the diseases", says Professor Mercè Pallàs.

The results could be explained with the several action mechanisms of LSL60101 and donepezil. Donepezil increases the levels of acetylcholine --a neurotransmitter related to memory and cognitive skills-- because it inhibits the enzyme in charge of its degradation (acetylcholinesterase). Also, LSL60101 is described as a I2 imidazoline receptor ligand, which have increased in the brain of people with dementia. Everything points out to the fact that the interaction of this drug with its receptor is involved in the generation of proinflammatory molecules that would increase the ongoing neuroinflammation in the disease. Therefore, I2 ligands would contribute to reduce the inflammation and thus, would slow the progression of the disease.

Both compounds were efficient in the recovery of the cognitive damage, but one of the objectives of the research study was to find whether the combination could improve the success of the treatment. "The results show that the SL60101-donepezil combined therapy is more efficient in some biomarkers of the disease. Therefore, it is possible that, with the combination of the suitable dose, we could reach an additive or even synergic effect", note the researchers.

Conducting new researches in the study will be a decisive factor to focus on the relation between I2 imidazoline receptors and Alhzeimer's and other diseases, and to boost the design of new therapeutic strategies based on the use of new selective I2-IR ligands to modulate the altered receptors in neurodegenerative pathologies.

Six antibody characteristics could help scientists identify which pregnant women are at risk of placental malaria infections, finds a study published today in eLife.

Malaria infections can be devastating for pregnant mothers, particularly during their first pregnancies. If malaria parasites invade the placenta, they can starve babies of nutrition, potentially causing low birth weight, preterm deliveries, stillbirths, and pregnancy loss. But not all women are susceptible to placental malaria infections, and the new study may help clinicians to identify those at risk and researchers to develop new therapies to protect pregnant women from malaria and related complications.

A protein made by malaria parasites called VAR2CSA allows them to attach to placental cells and invade the placenta. "Many women produce antibodies that can prevent this infection, and even those who have placental malaria during their first pregnancy are less likely to become infected during subsequent pregnancies because they have already developed protective antibodies," explains co-first author Dr Elizabeth Aitken, Research Officer at the Doherty Institute, University of Melbourne, Australia. "We set out to identify the features of these antibodies that help protect women from placental infections."

In their experiments, the research team used a machine learning technique to identify naturally acquired antibody features mid pregnancy that were associated with protection from placental malaria at delivery. They analysed 169 antibody features in 77 pregnant women from Madang, Papua New Guinea.

Of these features, they identified six that were associated with placental malaria protection. These fell into two broad groups: those related to preventing the parasites from binding to placental cells, and those that led to the destruction of infected blood cells. "Using these features, we created a model that could predict which pregnant women would develop placental malaria infections with 86% accuracy," says co-first author Timon Damelang, a PhD student at the Doherty Institute.

"These results suggest it is likely there are multiple pathways to protection against placental malaria," adds co-first author Amaya Ortga-Pajares, also a PhD student at the Doherty Institute.

"It will be interesting to learn whether this same combination of features can protect pregnant women from placental malaria infections in other populations," concludes senior author Professor Stephen Rogerson, Head of the Malaria Laboratory at the Doherty Institute, University of Melbourne. "This new insight is important for the development of novel vaccines or other treatments to protect pregnant women and their babies from the effects of malaria."

New insight on how our experiences during a task or interaction shape our current mood has been published today in the open-access eLife journal.

The study suggests that early experiences may have a larger effect on our mood than more recent events. These findings hold implications for the timing of events in experimental or clinical settings, and suggest new directions for mood interventions tailored to individual patients.

People routinely report on their moods during everyday activities and when they interact with clinicians providing mental health care. It is commonly believed that the most recent experiences during a task or interaction with someone else may have the strongest effect on how an individual feels at a given time. But in a series of experiments, researchers show that early experiences can have a more significant impact on someone's mood. The research team included first author and Postdoctoral Research Fellow Hanna Keren and colleagues at the Intramural Research Program of the National Institute of Mental Health (NIMH), National Institutes of Health, Bethesda, US.

To address the question of how the timing of an event can impact our current mood, Keren and colleagues began with a computational modelling approach. They developed a novel Primacy model, based on the concept that experiences occurring early in an interaction or game prevail over more recent ones in affecting our mood. They then pitted this model against a Recency model, based on the idea that more recent experiences have a stronger effect on mood. They showed that the Primacy model accounts more for self-reported mood when compared to the Recency and other computational models.

They also examined their models in relation to the moods of people of different ages, as well as healthy and depressed participants. To do this, they recruited a group of adult volunteers to participate in an online gambling game with small monetary rewards based on their success in the game. They invited the volunteers to report their moods using a sliding scale at several points during the game. In a second set of experiments, they recruited a group of adolescent volunteers to play a similar game in the laboratory while measuring these participants' brain activity using functional magnetic resonance imaging. They also collected data on whether the participants had depression, as this can also impact an individual's current mood.

The researchers found that early events during the game had the greatest impact on mood in both the adolescent and adult groups. This was also true for individuals with and without depression. Their imaging data also suggested that earlier experiences in the game 'switched on' parts of the frontal brain associated with moods, rather than later events. These results provided evidence for the neural encoding of the team's Primacy, but not Recency model.

Altogether, the findings raise some important questions, such as why adverse experiences early in a task or interaction may have lasting effects on an individual's mood. Future studies assessing the impact of events on mood over longer time periods might help answer these questions.

In the meantime, Keren and the team suggest their current work may have implications for the way clinicians providing mental health care interact with patients or assess the effectiveness of their treatment, as the timing of good and bad experiences may affect how patients feel about their treatment.

Rising nighttime temperatures are curbing crop yields for rice, and new research moves us closer to understanding why. The study found that warmer nights alter the rice plant's biological schedule, with hundreds of genes being expressed earlier than usual, while hundreds of other genes are being expressed later than usual.

"Essentially, we found that warmer nights throw the rice plant's internal clock out of whack," says Colleen Doherty, an associate professor of biochemistry at North Carolina State University and corresponding author of a paper on the work.

"Most people think plants aren't dynamic, but they are. Plants are constantly regulating their biological processes - gearing up for photosynthesis just before dawn, winding that down in the late afternoon, determining precisely how and where to burn their energy resources. Plants are busy, it's just difficult to observe all that activity from the outside."

And what researchers have learned is that the clock responsible for regulating all of that activity gets messed up when the nights get hotter relative to the days.

"We already knew that climate change is leading to increased temperatures globally, and that nighttime temperatures are rising faster than daytime temperatures," Doherty says. "We also knew that warmer nights hurt rice production. But until now, we had very little insight into why warmer nights are bad for rice.

"We still don't know all the details, but we're narrowing down where to look."

Research that addresses rice yield losses is important because rice is an essential crop for feeding hundreds of millions of people each year - and because a changing climate poses challenges for global food security.

To better understand how warm nights affects rice, Doherty worked with an international team of researchers - including Krishna Jagadish of Kansas State University and Lovely Lawas of the International Rice Research Institute - to study the problem in the field. The researchers established two study sites in the Philippines. Temperatures were manipulated in different areas of each study site using either ceramic heaters or heat tents.

A research team led by Jagadish used the ceramic heaters to maintain experimental plots at 2 degrees Celsius above the ambient temperature, and took samples from the rice plants every three hours for 24 hours. Control plots were not heated, but were also sampled every three hours during the same 24-hour period. These tests were repeated four times. The heat tents were later used to validate the results from the ceramic heater tests.

Meanwhile, a team led by Doherty found that more than a thousand genes were being expressed at the "wrong" time when nighttime temperatures were higher. Specifically, hotter nights resulted in hundreds of genes - including many associated with photosynthesis - becoming active later in the day. Meanwhile, hundreds of other genes were becoming active much earlier in the evening than normal, disrupting the finely tuned timing necessary for optimal yield.

"It's not clear what all of these genes do, but it is clear that these conflicting schedule shifts are not good for the plant," Doherty says.

The researchers found that many of the affected genes are regulated by 24 other genes, called transcription factors. Of those 24, four of the transcription factors were deemed most promising for future study.

"We need to do additional work to figure out exactly what's happening here, so that we can begin breeding rice that's resilient against warmer nights," Doherty says. "Rice is an important food crop. And other staple crops are also affected by hotter nights - including wheat. This isn't just an interesting scientific question, it's a global food security issue."

A team of neuroscientists at the Beckman Institute for Advanced Science and Technology led by Baher Ibrahim and Dr. Daniel Llano published a study in eLife that furthers our understanding of how the brain perceives everyday sensory inputs.

"There is a traditional idea that the way that we experience the world is sort of like a movie being played on a projector. All the sensory information that is coming in is being played on our cerebral cortex and that's how we see things and hear things," said Llano, a Beckman researcher and associate professor in the Department of Molecular and Integrative Physiology at the University of Illinois Urbana-Champaign.

However, quite a few studies over the years have challenged this traditional view of how we perceive the world. These studies present a new model: rather than projecting information onto the cortex, the thalamus might be selecting information that is already present in the cortex, based on our learned experiences.

Using a unique mouse brain slice that retains connectivity between three different regions of the brain (midbrain, thalamus, and cortex), Ibrahim and colleagues conducted a series of experiments that involved complicated techniques like electrophysiology, optogenetics, and computer modeling.

Ibrahim discerned that the neurons controlling which signals are relayed to the cortex are cortico-thalamic neurons that act through the thalamic reticular nucleus. These neurons descend from the cortex to the thalamus, making up a population of neurons that is not often talked about, but is nevertheless responsible for controlling what information is relayed to the cortex.

The implications of this research are far-reaching. It is possible to discern from this study that, amongst a veritable sea of sensory inputs, the brain uses these cortico-thalamic neurons to select which sensory inputs to relay up to the cortex via a "non-linear response." This results in humans paying attention to only those sensory inputs that are being relayed to the cortex. Hence, this publication brings to light the neuronal circuitry that is involved in perception-specific sensory information.

"Prior to us doing this particular study, other studies were showing the presence of these non-linear responses in the cortex in other sensory systems, like the visual system. Therefore, I suspect that what we discovered in the auditory system might be a generic mechanism that would be seen across sensory systems with the exception of olfaction," said Llano.

"Learning how to perform all these techniques correctly and efficiently to get reliable data was the most challenging part of this study," added Ibrahim.

Ibrahim, a postdoctoral research associate in Llano's lab, came from a pharmacological scientific background and was not previously trained in performing electrophysiological techniques. This posed unique challenges.

The study ultimately begs the question as to whether everyday sensory perception is a mixture of the internal models of the world that our brain is selecting based on cognitive demand and the input streams flowing from the outside world. This would be a very different way of understanding sensory perception as opposed to what is traditionally taught. Clarity of such concepts is fundamental to understanding situations where these processes of perceptions go awry, namely hallucinations.

The Beckman Institute's recent acquisition of a state-of-the-art multiphoton microscope renders a wide array of possibilities for moving this study forward. This microscope will allow scientists to image the living brain at the cellular level. This will allow Llano and colleagues to study the cerebral cortex of living animals at the cellular level, further allowing them to study hundreds of neurons at a time, and silence specific subpopulations of neurons and see how the responses change.

This study is another step towards understanding the infinitely complex organ that is our brain.

ROCHESTER, Minn. -- Mayo Clinic researchers are taking a close look at rare cases of inflammation of the heart muscle, or myocarditis, in young men who developed symptoms shortly after receiving the second dose of the Moderna or Pfizer messenger RNA (mRNA) COVID-19 vaccines. Several recent studies suggest that health care professionals should watch for hypersensitivity myocarditis as a rare adverse reaction to being vaccinated for COVID-19. However, researchers stress that this awareness should not diminish overall confidence in vaccination during the current pandemic.

While reports of post-vaccine myocarditis in some areas are higher than baseline, the imminent and greater risk for heart damage and death continues to be from becoming infected with COVID-19. Up to 60% of people who are seriously ill with COVID-19 experience injury to their heart, and nearly 1% of fit athletes who had a mild COVID-19 infection show myocarditis on an MRI.

A retrospective case series published in JAMA Cardiology studied 23 men in the U.S. military who were hospitalized with myocarditis symptoms within four days of receiving the second dose of a messenger RNA COVID-19 vaccine. Three of the patients previously had been infected with COVID-19, and their symptoms started after the first dose of the vaccine. The cases occurred between January and April. Sixteen had received the Moderna vaccine and seven had received the Pfizer vaccine. For context, it is important to note that the military administered more than 2.8 million doses of messenger RNA COVID-19 vaccines during that time.

All 23 military patients had symptoms of severe chest pain and significantly elevated cardiac troponin levels, which is a protein marker used to measure heart damage. Each patient rapidly recovered, which, combined with the timing and symptoms, supports the diagnosis of hypersensitivity myocarditis. This unusual type of myocarditis is usually related to a drug allergy, but it has been researched in relation to the smallpox vaccine.

"Hypersensitivity myocarditis following vaccination is rare, with the exception of smallpox vaccine. The risk of myocarditis after receiving mRNA vaccine is far less than the risk of myocarditis following actual COVID-19 infection," says Leslie Cooper, M.D., chair of the Department of Cardiology at Mayo Clinic in Florida. Dr. Cooper is senior author of the study, which was conducted with U.S. military medical centers.

Another observational case study recorded details of eight men between the ages of 21 and 56 who were hospitalized with chest pain and diagnosed with myocarditis by laboratory and cardiac MRI. The patients developed symptoms, starting with a fever, within two to four days of receiving their second dose of a COVID-19 vaccine. One patient who had previously recovered from COVID-19 had symptoms after the first dose. All eight patients in the study recovered from the effects of myocarditis and no longer had chest pain. The findings, co-authored by Dr. Cooper with researchers from Mayo Clinic and other medical institutions in the U.S. and Italy, are published in Circulation.

"People of all ages should choose to get a COVID-19 vaccine because the risks are extremely low compared to the benefits. Additionally, the growing body of research shows that vaccine-associated myocarditis resolves quickly in almost all cases," says Dr. Cooper.