Culture

ROCKVILLE, Md. - June 10, 2021 - The Association for Molecular Pathology (AMP), the premier global, molecular diagnostic professional society, today published consensus recommendations to aid in the design and validation of clinical CYP2D6 assays, promote standardization of testing across different laboratories and improve patient care. The manuscript, "Recommendations for Clinical CYP2D6 Genotyping Allele Selection: A Joint Consensus Recommendation of the Association for Molecular Pathology, College of American Pathologists, Dutch Pharmacogenetics Working Group of the Royal Dutch Pharmacists Association, and European Society for Pharmacogenomics and Personalized Therapy," was released online ahead of publication in The Journal of Molecular Diagnostics.

The AMP Pharmacogenetics (PGx) Working Group is developing a series of guidelines designed to help standardize clinical testing for frequently used genotyping assays. The latest CYP2D6 report builds on the earlier recommendations for clinical genotyping of CYP2C19, CYP2C9, and genes important for warfarin testing. The recommendations should be implemented together with other relevant clinical guidelines such as those issued by the Clinical Pharmacogenetics Implementation Consortium (CPIC), Dutch Pharmacogenetics Working Group (DPWG), Canadian Pharmacogenomics Network for Drug Safety (CPNDS), and the American College of Medical Genetics and Genomics (ACMG), which mostly focus on the interpretation of PGx test results and therapeutic recommendations for specific drug-gene pairs.

"CYP2D6 is known to be responsible for the metabolism of many commonly prescribed medications including some antidepressants, atypical and typical antipsychotics, beta-blockers, opioids, antiemetics, and atomoxetine," said Victoria M. Pratt, PhD, Professor and Director of Pharmacogenetics and Molecular Genetics Laboratories, Indiana University School of Medicine, and AMP PGx Working Group Chair. "The ultimate goal of the AMP PGx Working Group is to promote standardization of PGx gene/allele testing across clinical laboratories. While the CYP2D6 gene is especially complex, with this latest report, we have been able to define a minimum set of variants that should be included in all future clinical CYP2D6 PGx genotyping assays."

Similar to the previous reports in the series, the CYP2D6 genotyping guideline offers a two-tier categorization of alleles that are recommended for inclusion in clinical PGx genotyping assays. Using criteria such as allele frequencies in different populations and ethnicities, the availability of reference materials, and other technical considerations, the AMP PGx Working Group recommended a minimum set of alleles and their defining variants that should be included in all clinical CYP2D6 genotyping tests (Tier 1). The team also defined a Tier 2 list of optional alleles that do not currently meet one or more of the criteria for inclusion in Tier 1. These recommendations are meant to be a reference guide and not to be interpreted as a restrictive list. AMP intends to update these recommendations as new data and/or reference materials become available.

"AMP is committed to collaborating with the broader laboratory community to continuously improve professional PGx practices amidst a rapidly evolving molecular diagnostic landscape," said Antonia R. Sepulveda, MD, PhD, AMP President and Professor and Chair of the George Washington School of Medicine Department of Pathology. "Standardizing clinical testing for frequently used PGx genotyping assays will improve concordance across laboratories and enable healthcare professionals to provide high-quality patient care."

(Boston)--Medical education aspires to mitigate bias in future professionals by providing a robust curriculum that includes perspectives and practices for caring for sexual and gender minority (SGM) populations, including lesbian, gay, bisexual, transgender and intersex (LGBTQI) persons. To provide medical schools with a more systematic, uniform approach to teaching these topics in their curriculum, the Association of American Medical Colleges (AAMC) in 2014 published 30 SGM competencies and topics that curricula should address. However, implementation of these ideals remains challenging.

Building off the AAMC's comprehensive resource guide, medical education leaders at Boston University School of Medicine (BUSM) have developed a curriculum assessment tool to efficiently assess whether a medical school adequately incorporates recommended SGM core competencies.

"Medical schools vary in how they cover SGM topics and to what extent graduating students feel prepared to meet the needs of these populations. Medical school leaders motivated to improve curricula on caring for SGM populations must survey their school's current curricula to identify their school's strengths and opportunities for improvement," said corresponding author Ann Zumwalt, PhD, associate professor of anatomy and neurobiology at BUSM and chair of the Gender and Sexual Diversity Vertical Integration Group (GSD VIG).

In 2018, the school convened the GSD VIG, comprising a group of BUSM faculty and students with experience and expertise regarding SGM health, to examine the state of BUSM's curriculum on SGM health. The group distilled the 30 AAMC competencies into 12 SGM topic areas that should be addressed in any medical school curriculum. They then developed the SGM Curriculum Assessment Tool (SGM-CAT), which employs targeted curriculum assessment questions to assess whether these topic areas are addressed within the curriculum--and, if they are, how and where.

This tool was distributed to all course and clerkship directors responsible for the required curriculum at BUSM to investigate where these core topics are addressed. The curriculum assessment tool identified several strengths in the pre-clerkship and clerkship curricula, including faculty willingness and enthusiasm to include SGM topics, but also revealed that some SGM topics are underrepresented in the BUSM curriculum.

"What is exciting about our tool is that we used our proficiency to distill the 30 AAMC competencies into 12 easily understandable topics that should be taught in any curriculum. We then surveyed all course and clerkship directors on whether they teach any of those 12 topics. The process/tool we developed is a straightforward way to get a snapshot of what is being taught where across the entire curriculum," added Zumwalt.

"As it is still not a requirement of medical training, identifying where SGM content even exists in medical schools is extremely difficult. This tool aims to easily and quickly reveal where SGM content is addressed in undergraduate medical education, thereby allowing for more rapid and comprehensive interventions to improve training," explained co-author Carl Streed, Jr., MD, MPH, FACP, assistant professor of medicine at BUSM and a primary care physician and research lead in the Center for Transgender Medicine & Surgery at Boston Medical Center (BMC).

According to the researchers, many faculty may miss opportunities to teach about SGM health because they do not recognize how the material fits with their topic. "The tool was designed to be used by individuals who are less familiar with SGM health and makes curricular change easier by helping users understand how SGM health is incorporated into existing curricula," added Jenny Siegel, MD, assistant professor of medicine at BUSM and medical director, Center for Transgender Medicine & Surgery at BMC.

Breakthrough in metamaterials: for the first time in the world, researchers at Tel Aviv University developed an innovative nanotechnology that transforms a transparent calcite nanoparticle into a sparkling gold-like particle. In other words, they turned the transparent particle into a particle that is visible despite its very small dimensions. According to the researchers the new material can serve as a platform for innovative cancer treatments.

In a new paper published in Advanced Materials, an international team of scientists, coordinated by Dr. Roman Noskov and Dr. Pavel Ginzburg from the Iby and Aladar Fleischman Faculty of Engineering at Tel Aviv University, Prof. Dmitry Gorin from the Center for Photonics and Quantum Materials at the Skolkovo Institute of Science and Technology (Skoltech) and Dr. Evgeny Shirshin from M.V. Lomonosov Moscow State University, has introduced the concept of biofriendly delivery of optical resonances via a mesoscopic metamaterial, a material with properties that are not found in nature. This approach opens promising prospects for multifunctionality in biomedical systems, allowing the use of a single designer-made nanoparticle for sensing, photothermal therapy, photoacoustic tomography, bioimaging, and targeted drug delivery.

"This concept is the result of cross-disciplinary thinking at the interface between the physics of metamaterials and bioorganic chemistry, aiming to meet the needs of nanomedicine. We were able to create a mesoscopic submicron metamaterial from biocompatible components that demonstrates strong Mie resonances covering the near-infrared spectral window in which biological tissues are transparent," says Dr. Roman Noskov.

The nanostructures capable of nanoscale light localization as well as performing several functions are highly desirable in a plethora of biomedical applications. However, biocompatibility is typically a problem, as engineering of optical properties often calls for using toxic compounds and chemicals. The researchers have resolved this issue by employing gold nanoseeds and porous vaterite (calcium carbonate) spherulites, currently considered promising drug-delivery vehicles. This approach involves controllable infusion of gold nanoseeds into a vaterite scaffold resulting in a mesoscopic metamaterial - golden vaterite - whose resonance properties can be widely tuned by changing the quantity of gold inside the vaterite. Additionally, high payload capacity of vaterite spherulites allows simultaneous loading of both drugs and fluorescent tags. To exemplify the performance of their system, the researchers demonstrated efficient laser heating of golden vaterite at red and near?infrared wavelengths, highly desirable in photothermal therapy, and photoacoustic tomography.

Prof. Pavel Ginzburg summarizes: "This novel platform enables the accommodation of multiple functionalities - as simple add-ons that can be introduced almost on demand. Alongside optical imaging and thermotherapy, MRI visibility, functional biomedical materials and many other modalities can be introduced within a miniature nano-scale particle. I believe that our collaborative efforts will lead to in-vivo demonstrations, which will pave the way for a new biomedical technology."

Through the biological fixation of the element nitrogen by the enzyme nitrogenase, organisms gain access to molecular nitrogen (N2) in the Earth's atmosphere, which is essential for building cellular structures. In addition, a vanadium-dependent variant of nitrogenase can reduce the toxic gas carbon monoxide (CO) to hydrocarbons. These reductions of N2 and CO are among the most important processes in industrial chemistry, as they are used to produce both fertilizers and synthetic fuels. However, researchers have not yet been able to decipher the different pathways of the two reactions. Dr. Michael Rohde from Prof. Dr. Oliver Einsle's team at the Institute of Biochemistry at the University of Freiburg, in collaboration with two research groups at Freie Universität Berlin, has now been able to show how the active site of the vanadium-dependent nitrogenase is able to bind two CO molecules simultaneously, thereby creating the basis for combining the spatially adjacent carbon atoms of both molecules in a reductive process. The researchers recently presented their results in the journal Science Advances.

The industrial reductions of N2 and CO - known as the Haber-Bosch and Fischer-Tropsch processes, respectively - require high temperatures and pressure. While N2 reduction leads to the bioavailable product ammonium (NH4+), at least two carbon atoms combine during the conversion of CO. The predominant reaction product is ethylene (ethene, C2H4), a colorless gas that plays an important role not only in fuels but also in the production of plastics. Although the cleavage of an N-N bond in nitrogen fixation is chemically quite fundamentally different from the formation of a C-C bond in CO reduction, scientists previously suspected that nitrogenase uses the same basic mechanistic principles for both reactions.

In a previous work, the team led by Rohde and Einsle used nitrogenase to react with CO gas, resulting in the specific binding of a single molecule. In their current study, which builds on this work, the researchers show that they gassed crystals of this first state with CO under pressure and then subjected them to X-ray crystallographic analysis. This allowed them to directly observe how a second CO molecule binds. "The form of nitrogenase obtained in this way, with two CO molecules at the active site, probably represents a blocked state," Rohde explains, "but it provides direct clues to the mechanism of the enzyme." As a result, Einsle's team can now outline a detailed mechanism of CO reduction through nitrogenase.

MINNEAPOLIS/ST.PAUL (06/10/2021) -- New findings from the University of Minnesota Medical School are helping uncover why some people are more likely to be overweight and develop Type 2 diabetes -- and it starts in the womb.

Previous association studies have shown that low birthweight among infants is a strong determinant for eventual obesity and Type 2 diabetes. The placenta of infants with a low birthweight have reduced levels of mTOR (mechanistic target of rapamycin), and the placenta of bigger infants have increased levels of mTOR. Building off of that research, a U of M Medical School study, published in JCI Insight, is the first to directly implicate mTOR, a nutrient-sensor protein in the placenta, as a possible regulator of an infant's birthweight.

"It is clear from human and preclinical studies that Type 2 diabetes has fetal origins, but we do not yet know the mechanisms of how this programming of metabolic dysfunction or Type 2 diabetes occurs," said senior author, Emilyn Alejandro, PhD, an associate professor in the Department of Integrative Biology and Physiology. "Our study is the first to show a direct role of a placental protein, like mTOR."

They found that in preclinical studies:

- After eliminating mTOR in the placenta, female offspring had lower birthweights and had an increased risk for obesity and insulin resistance in adulthood.

- In contrast, after increasing mTOR signaling in the placenta, female adult offspring were protected from high-fat diet induced obesity.

"A causal relationship between placental mTOR and the metabolic health of the offspring has not been tested before, and our study suggests that manipulating mTOR in the placenta is sufficient to cause permanent and lasting impact on the health trajectory of the offspring" said Brian Akhaphong, first author and a post-baccalaureate trainee in the Alejandro Lab. "Our hope is that we can identify proteins that we may target therapeutically through maternal health to reduce the prevalence of Type 2 diabetes."

The research team will continue their study, probing which metabolic tissues in the offspring are permanently impacted by placental mTOR signaling. Megan Beetch, PhD, a postdoctoral fellow, will look at the epigenetics, or heritable changes in gene expression, that do not involve changes to the underlying DNA sequence.

Genova (Italy) 10 June, 2021 - The U-Vip (Unit for Visually Impaired People) research team led by Monica Gori at the IIT- Istituto Italiano di Tecnologia (Italian Institute of Technology) has recently published a study which shows for the first time how children aged from 3 to 5 years old have problems in recognising the emotions of people wearing surgical masks. This collateral effect of the preventive measures linked to the Covid-19 health emergency could influence the correct development of children's capabilities of social interaction. The research paper has been published in Frontiers in Psychology.

The use of facemasks for children within the context of the COVID-19 pandemic was a focus of a document compiled by the World Health Organisation (WHO) and UNICEF to provide guidance for decision-makers and authorities in public and professional fields, discouraging exposure to the use of facemasks when dealing with children aged up to five years old. In addition, even for older children, WHO recommends giving careful consideration to the benefits of wearing facemasks in comparison with the potential damage that could include social and psychological problems, and difficulties in communication and learning.

The study by the IIT research team led by Monica Gori regards this context, and, for the first time it focuses on pre-school age group and it helps define the measures that can be taken to reduce the impact of the use of surgical masks amongst children. In fact, even though from 3 to 5 years of age, wearing facemasks is not mandatory, children are in any case exposed to the use of such preventive measures in various everyday social and educational contexts.

The IIT researchers prepared a quiz containing images of people with and without facemasks, and displayed them by computer, tablet or smartphone to 119 individuals comprising 31 children aged between 3 and 5 years old, 49 children between 6 and 8 years old, and 39 adults between 18 and 30 years old. The subjects, independently or with parental assistance in the case of the youngest participants, were asked to try to recognise the faces' expressions, with and without facemask, conveying different emotions such as happiness, sadness, fear and anger.

The results showed that children aged between 3 and 5 years old are capable of recognising facial expressions conveying happiness and sadness on only 40% of occasions when the faces are covered by a facemask. The percentages were higher for other age groups: children aged from 6 to 8 years old (55-65%) and adults (70-80%) but in general, all age groups showed a degree of difficulty in interpreting these emotions expressed while the face was partially covered by a facemask. As regards the other emotions, there were better results, but we can say that the age group that finds it hardest to recognise emotions expressed from behind a facemask is that of children in pre-school age.

"The experiment was performed in the earliest phases of the 2020 pandemic, and at that time facemasks were still a new experience for everyone.", comments Monica Gori, "Children's brains are highly flexible, and at the moment we are performing tests to ascertain whether children's understanding of emotions has increased or not", concludes Gori.

"In the study, we worked with children and adults with no forms of disability", explains Maria Bianca Amadeo, IIT researcher and co-author of the research study, "of course, these observations are even more important when considering children affected by disabilities". "Indeed", explains Lucia Schiatti, IIT researcher and co-author of the study "for example visual impairment implies difficulties in social interaction. For such individuals in particular, it will be even more necessary to concentrate on possible preventive measures or specific rehabilitation activities".

Over the next few years, it will be essential to perform work designed to explore the actual impact of this preventive health measure on children's ability to interact, both those affected by disabilities and those without disabilities.
In the meantime, the IIT study suggests considering the use of transparent facemasks for all operators in contact with children in the 3-5 year-old age group, or the formulation of specific training activities designed to teach children how to recognise emotions purely through observation of the eyes.

Because of a phenomenon called gravitational locking, the Moon always faces the Earth from the same side. This proved useful in the early lunar landing missions in the 20th century, as there was always a direct line of sight for uninterrupted radiocommunications between Earth ground stations and equipment on the Moon. However, gravitational locking makes exploring the hidden face of the moon--the far side--much more challenging, because signals cannot be sent directly across the Moon towards Earth.

Still, in January 2019, China's lunar probe Chang'e-4 marked the first time a spacecraft landed on the far side of the Moon. Both the lander and the lunar rover it carried have been gathering and sending back images and data from previously unexplored areas. But how does Chang'e-4 probe communicate with the Earth? The answer is Queqiao, a relay communications satellite, explains Dr. Lihua Zhang from DFH Satellite Co., Ltd., China.

As explained by Dr. Zhang in a review paper recently published in Space: Science & Technology, Queqiao is an unprecedented satellite designed specifically for one purpose: to act as a bridge between Chang'e-4 probe and the Earth. Queqiao was launched in 2018 and put into orbit around a point 'behind' the Moon. This point is known as the Earth-Moon Libration point 2, where a special case of gravitational balance allows Queqiao to maintain an orbit such that it has almost constant direct line of sight with both the far side of the Moon and the Earth. Getting the satellite into this peculiar orbit required careful planning and maintenance management, and the success of this operation set a precedent for future attempts at putting satellites in orbit around other Earth-Moon libration points.

From its stable place in space, Queqiao helped guide the soft-landing and surface operations of Chang'e-4 probe and has been our intermediary with it ever since. The satellite is equipped with two different kinds of antennas: a parabolic antenna and several spiral antennas. The former, which has a large diameter of 4.2 m, was designed to send and receive signals on the X band (7-8GHz) to and from the rover and lander on the surface of the Moon. Its large size is related the expected noise levels and the low intensity of the transmissions that are sent by surface equipment.

On the other hand, the spiral antennas operate on the S band (2-4 GHz) and communicate with Earth ground stations, forwarding commands to the lunar surface equipment and exchanging telemetry and tracking data. Most notably, all these different links can transmit and receive simultaneously, making Queqiao highly versatile. The review paper addresses other important design considerations for Queqiao and future relay satellites, such as the use of regenerative forwarding, the various link data rates involved, and data storage systems for when no Earth ground station is accessible.

Over two years of exploration, a great amount of data has been received from the rover and lander through Queqiao. "Scientists in both China and other countries have conducted analysis and research based on the retrieved data, and they have produced valuable scientific results. The longer the operational life of Queqiao, the more scientific outcomes will be achieved," remarks Dr. Zhang. Based on current predictions, Queqiao should be operable on mission orbit for at least five years.

Dr. Zhang also addressed the prospects for future lunar missions and how relay communication systems should evolve to support them. Many unexplored areas on the Moon, such as the largest crater at the South Pole, call for multiple relay satellites to maintain constant communication links, which poses an expensive and time-consuming challenge. But what if relay satellites were suitable for more than a single mission? "A sustainable communication and navigation infrastructure should be established to benefit all lunar missions rather than dealing with each mission independently," comments Dr. Zhang, "This infrastructure should adopt an open and extensible architecture and provide flexible, interoperable, cross-supportable, and compatible communications services, which are critical to the success of future lunar explorations." It's likely that future endeavors on the far side of the Moon will be a test on how well we can cooperate to unveil the secrets of our natural satellite.

Plants are constantly exposed to microbes: pathogens that cause disease, commensals that cause no harm or benefit, and mutualists that promote plant growth or help fend off pathogens. For example, most land plants can form positive relationships with arbuscular mycorrhizal fungi to improve nutrient uptake. How plants fight off pathogens without also killing beneficial microbes or wasting energy on commensal microbes is a largely unanswered question.

In fact, when scientists within the field of Molecular Plant-Microbe Interactions were asked to come up with their Top 10 Unanswered Questions, the #1 question was "How do plants engage with beneficial microorganisms while at the same time restricting pathogens?" Put more simply, how do plants tell good microbes from bad and what do they do about it? As part of a Top10MPMI review series in the open access MPMI Journal, this question of how plants and microbes engage in symbiosis was recently interrogated by Dr. Cara Haney and Dr. David Thoms, microbiologists at the University of British Columbia, in collaboration with Dr. Yan Liang at Zhejiang University in China.

"Maintaining a balance in plant disease resistance where plants can fight off pests and pathogens but still engage with microbes that can help with nutrient uptake is essential for the health of our crops," emphasizes Haney. To fully engage with such a large question, paradigms are needed to drive specific research questions towards the unanswered pieces. As Haney says, "this question is so broad, I think the review raises more questions than it answers. We attempted to highlight much of what was known, but also what wasn't known and to provide paradigms and models that could be frameworks going forward." In a proposed framework for considering mechanisms of symbiotic engagement, Haney, Thoms, and Liang distinguish three principles: chemical selection with metabolites, dual receptor recognition, and tuning of an immune thermostat.

Plants first use metabolite compounds like antimicrobials and chemical signals to recruit beneficial organisms and restrict pathogens, but not all pathogens are excluded. Once plant and microbe are in contact, Thoms proposes that "a dual input model" is used by the plant to distinguish both the type of microbe (bacterial, fungal, or nematode) and the lifestyle (mutualist, commensal, or pathogen). Microbes can be detected by receptor proteins on the surface of plant cells. When receptor proteins detect a piece of fungal cell wall known as chitin, the plant discovers a fungal microbe is present. But as chitin, and other microbe-associated molecular patterns (MAMPS), are often shared among microbes, they are insufficient signals to distinguish commensals from pathogens according to Thoms.

"Unlike most animals, plants do not have an adaptive immune system. However, plant genomes contain many more innate immune receptors than animals," Liang explains. "Plants also use similar receptors to sense signaling molecules from beneficial microbes, environments, as well as their own cells." So, additional receptors use a second layer of information to identify pathogens versus mutualists. Symbiosis receptors can identify signaling molecules specifically produced by beneficial microbes, while immune receptors can identify pathogen proteins intended to shut down plant defense. Addressing the need to know both the type and lifestyle of a microbe, Thoms remarks, "I think it's cool that plants can perceive so many types of MAMPs across different kingdoms of life and I think one use of that is recognizing where the microbe is coming from to give the appropriate physiological response." Essentially, a plant cell follows a flowchart to determine what reaction is needed in response to the type and lifestyle of microbe it perceives.

Yet, a plant can simultaneously engage with multiple microbes that require different responses, making it more complicated than following the flowchart directly. Energy use for immunity and symbiosis must be balanced based on present microbes and current plant needs. So, the remaining piece of the story is a "normal immune setpoint." "It is important to understand what this is and how it can be adjusted over a plant's life in order to maximize yields of our crops," explain Haney. Because of the impact of the environment and nutrient stress as well, how plants decide to use resources to engage in symbiosis or prevent infection is perhaps one of the biggest areas for exploration.

How to identify and respond to different microbes in variable environments is not a problem unique to plants. "Many living things, ranging from plants to humans, are faced with the challenge of engaging with beneficial microbes while restricting pathogens," highlights Haney. "As a result, paradigms in plant-microbe interactions may shed light on eukaryotic interactions with microbes in diverse organisms."

An exploratory investigation into the behavior of materials with desirable electric properties resulted in the discovery of a structural phase of two-dimensional (2D) materials. The new family of materials are electrides, wherein electrons occupy a space usually reserved for atoms or ions instead of orbiting the nucleus of an atom or ion. The stable, low-energy, tunable materials could have potential applications in nanotechnologies.

The international research team, led by Hannes Raebiger, associate professor in the Department of Physics at Yokohama National University in Japan, published their results on June 10th as frontispiece in Advanced Functional Materials.

Initially, the team set out to better understand the fundamental properties of a 2D system known as Sc2CO2. Containing two atoms of metallic scandium, one atom of carbon and two atoms of oxygens, the system belongs to a family of chemical compounds collectively referred to as MXenes. They are typically composed of a carbon or nitrogen layer one atom thick sandwiched between metal layers, dotted with oxygen or fluorine atoms.

The researchers were particularly interested in MXene Sc2CO2 due to the predictions that, when structured into a hexagonal phase, the system would have desired electrical properties.

"Despite these fascinating predictions of hexagonal phases of Sc2CO2, we are not aware of its successful fabrication as of yet," said Soungmin Bae, first author and researcher in the Department of Physics at Yokohama National University. "Analyzing its fundamental properties, we discovered a completely new structural phase."

The new structural phase results in new electride materials. The atomic-thin 2D structural phase is described as tiled shapes forming the central carbon plane. The previously predicted shape was a hexagon, with a carbon atom at every vertex and one in the middle. The new materials have a rhombus-like shape, with electrons at the vertices and a carbon trimer -- three carbon atoms in a row -- in the middle.

"Carbon is one of the most common materials on our planet, and quite important for living beings, but it is hardly ever found as trimers," Raebiger said. "The closest place where carbon trimers are typically found is interstellar space."

The overall shape is less symmetric than the previously described hexagonal structure, but it is more symmetric with regard to the central plane. This structure offers unique characteristics due to the appearance of the new family of electrides, according to Raebiger.

"Electrides contain electrons as a structural unit and often are extremely good electrical conductors," Raebiger said. "The present family of electrides are insulators, and while most insulators can be made conductive by adding or removing electrons, these materials simply become more insulating."

MXenes are particularly attractive as a material, because they can be reconfigured with other metallic elements to offer a cornucopia of properties, including tunable conductivity, various forms of magnetism, and/or accelerate chemical reactions as catalysts. On top of this, they are ultra-thin sheets only a few atoms thick, that is, 2D materials. The newly discovered electrides have electrons in lattice voids between atoms and ions, which can be readily emitted into surrounding space, such as the electron sources for large particle accelerators, as well as be borrowed to catalyze a specifically desired chemical reaction.

"We made this discovery because we wanted to understand how these materials work better," Bae said. "If you encounter something you don't understand, dig deeper."

Co-authors include William Espinosa-García and Gustavo M. Dalpian, Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Brazil; Yoon-Gu Kang and Myung Joon Han, Department of Physics, Korea Advanced Institute of Science and Technology; Juho Lee and Yong-Hoon Kim, Department of Electrical Engineering, Korea Advanced Institute of Science and Technology; Noriyuki Egawa, Kazuaki Kuwahata and Kaoru Ohno, Department of Physics at Yokohama National University; and Mohammad Khazaei and Hideo Hosono, Materials Research Center for Element Strategy, Tokyo Institute of Technology. Espinosa-García is also affiliated with Grupo de investigación en Modelamienot y Simulación Computacional, Facultad de Ingenierías, Universidad de San Buenaventura-Medellín.

The Iwaki Scholarship Foundation; São Paulo Research Foundation; Korea's National Research Foundation, Ministry of Science and ICT and Ministry of Education; KAIST (formerly the Korea Advanced Institute of Science and Technology); and Samsung Research Funding & Incubation Center of Samsung Electronics funded this work.

Music is a tool that has accompanied our evolutionary journey and provided a sense of comfort and social connection for millennia. New research published today in the American Psychologist provides a neuroscientific understanding of the social connection with a new map of the brain when playing music.

A team of social neuroscientists from Bar-Ilan University and the University of Chicago introduced a model of the brain that sheds light on the social functions and brain mechanisms that underlie the musical adaptations used for human connection. The model is unique because it focuses on what happens in the brain when people make music together, rather than when they listen to music individually.

The research was inspired by creative efforts of people around the world to reproduce music-making together while social distancing during the COVID-19 pandemic. This included people singing songs in unison from balcony to balcony, group singing on video conferencing platforms such as Zoom, and live living room concerts by the likes of Yo Yo Ma, Chris Martin from Coldplay, and Norah Jones.

The team fused the latest advances in social neuroscience and the field of music, including evolutionary theory. They synthesized these advances and highlighted five key functions and mechanisms of the brain that contribute to social connection through music.

These are (1) empathy circuits, (2) oxytocin secretion, (3) reward and motivation, including dopamine release, (4) language structures, and (5) cortisol. These five functions and mechanisms involve at least 12 important brain regions and two pathways which are mapped here.

Empathy helps us to tune into how other people are thinking and feeling, and can be improved through interpersonal musical coordination.

Oxytocin is sometimes called the "love hormone" because it contributes to our sense of feeling socially bonded with others. It is secreted when people sing together, even when the singing is improvised.

Dopamine is a neurotransmitter that produces a sense of pleasure and is released during musical anticipation and expectation, and pivotal for our sense of reward and motivation.

Language structures in the brain are involved in back-and-forth musical dialogue (sometimes referred to as "call" and "response").

Cortisol is a hormone that contributes to stress, but it is decreased in the brain when people sing together and when they listen to music together in groups.

The research provides the groundwork for an emerging field called the "social neuroscience of music", which builds on the previously established cognitive neuroscience of music, which largely focuses on music listening.

The authors say a better understanding of the social neuroscience of music can play an important role for helping to improve social bonding around the world, particularly in cultures that are in conflict. They conclude that music is a powerful tool that can bring individuals together, promote empathy and communication, and heal social divisions. They say that a better scientific understanding of how music provides brain-to-brain social connections helps highlight that music isn't mere entertainment, but instead is a core feature of human existence with important social implications.

Dr. David Greenberg, who led the research, is a social neuroscientist, professional musician, and Zuckerman Postdoctoral Scholar at Bar-Ilan University in Israel. He says, "Music connects us to our humanity. Through social neuroscience, we can discover that our sense of social connection isn't just subjective, but that it is rooted in important brain mechanisms. Especially in a time when there is so much social division around the world, we need to find new ways to to bridge cultures in conflict. Music is one of those ways. We hope our research will lead to more grass-roots programs like the West-Eastern Divan Orchestra and the Jerusalem Youth Chorus, which bring people from differing cultures together through music."

Dr. Ilanit Gordon, an Associate Professor at the Department of Psychology and Director of the Social Neuroscience Lab at the Gonda (Goldschmied) Multidisciplinary Brain Research Center at Bar-Ilan, says: "Human sociality is rooted in our biological makeup. Through music we can connect and interact with others, and via the scientific exploration of the neurobiological basis of music, we can further our understanding of major issues in social neuroscience."

Jean Decety, the Irving B. Harris Distinguished Service Professor in Psychology and Psychiatry, and director of Child Neurosuite at the University of Chicago, says, "Music is a fundamental part of our evolution, allowing for unique expressions of social ties. It can strengthen cohesion and mutual trust between people by signaling shared values. It is quite fascinating to understand the neurobiological mechanisms of music."

GRAND RAPIDS, Mich. (JUNE 10, 2021) -- Much like a supply truck crossing the countryside, the misfolded proteins that damage neurons in Alzheimer's disease travel the "roads" of the brain, sometimes stopping and sometimes re-routing to avoid roadblocks, reports a study published in Science Advances by researchers at Van Andel Institute and University of Pennsylvania.

The findings shed light on how tau proteins, which form tangled clumps that damage brain cells in Alzheimer's, move through the brain. The study also provides new insights into why some areas of the brain are more vulnerable to damage than other areas.

"While the interconnected structure of the brain is essential to its function, these misfolded proteins commandeer that structure to travel through the brain and cause progressive degeneration," said Michael X. Henderson, Ph.D., an assistant professor at Van Andel Institute and corresponding author of the study. "By understanding how these proteins travel through the brain and what causes certain neurons to be at risk for damage, we can develop new therapies that can be directed to the right place at the right time to have maximal impact on disease progression."

Using models of Alzheimer's disease, the team mapped misfolded tau proteins as they progressed through the brain. They found that tau pathology moved from region to region along the brain's neural networks, which are similar to biological highways, but that it did not travel to every connected region.

To find out why some areas of the brain seemed to resist the proteins' spread, the team turned to gene expression patterns.

They identified some genes that were expressed more in regions that had more tau pathology than expected from protein spread alone. By understanding the genetic factors that control protein accumulation in the brain, the team hopes to identify ways to interfere with misfolded protein movement and slow or stop the progression of Alzheimer's and similar neurodegenerative diseases.

"We used these network models to test our hypothesis that tau spreads both forward and backward along connections between brain regions," said Eli Cornblath, Ph.D., an M.D./Ph.D. student at University of Pennsylvania and the study's first author. "After using our models to account for this two-way spreading process, we found several genes that could help inform new molecular targets to clear or prevent these protein aggregates from forming."

Just as the governor announced the start of python hunting season in Florida this month, researchers at the University of Central Florida have published a first- of-its-kind study that shows that near-infrared (NIR) spectrum cameras can help hunters more effectively track down these invasive snakes, especially at night.

The snakes, which can reach 26 feet in length and 200 pounds, have invaded the Everglades in Florida -- threatening native species and disrupting the ecosystem. The number of common native species observed in the Everglades since the snakes were first discovered in the 1990s dropped in some species by 90% through 2010, according to an earlier study. Since then, the state has been implementing mitigation strategies and encouraging residents to hunt down the massive snakes. On average snakes removed from the Everglades are about eight feet long, according to the Florida Fish and Wildlife Conservation Commission.

The new study found that by using NIR cameras, pythons could be detected 20 percent farther away than with visible cameras. Researchers say that with more work they may be able to develop an automated snake detection system. That could be a game changer especially since the pythons are marching northward and could threaten native species as far north as Virginia and Texas to the west.

"Manual removal of Burmese pythons has been the most effective management strategy, but snakes are difficult to see due to their natural camouflage," says Kyle Renshaw, a co-author of the study and an assistant professor at CREOL - UCF's College of Optics and Photonics. "NIR cameras will help python hunters find and remove pythons. These small, inexpensive cameras could be mounted on trucks or drones to help catch the hard-to-find pythons. Using cameras also opens the possibility for automated detection using computer algorithms to search the imagery faster and more comprehensively than the hunters can do on their own."

Jennifer Hewitt, a graduate student in Renshaw's lab led the study, which was published this week in the journal Applied Optics.

This research is one example showing how cameras can be "tuned" to improve performance of a specific task, the researcher say. The detection band, time constants, lens parameters, image processing and algorithms provide a rich set of variables to optimize a camera system for a particular application. The work with the snakes was based on viewing from a stationary position, but the team hopes to expand its work to include moving sensors.

"That could have big applications in search & rescue, explosives detection, border security, etc.," Renshaw says. "Jen is developing and testing models for time-limited search using a moving camera as we speak as part of her thesis."

How did they do it?

The work builds on previous spectral reflectivity characterization of pythons conducted at CREOL by then UCF Professor Ron Driggers.

Hewitt collected images of pythons at different locations and with different background scenery. Images were collected using two similar cameras that differed only in their spectral sensitivity. Images were taken in the daytime and at night at 10 different locations with similar foliage.

Hewitt then wrote software to randomly present images to the volunteers, asking them to "click" on the snake in the scene. Some scenes had no snakes. User responses were collected and analyzed. Volunteers spent an hour looking at imagery on a computer to locate pythons and clicking on the python image.

"For both day and night conditions, volunteers were able to detect the pythons further away with NIR than with visible," Hewitt says. "From here, we are continuing to fine tune the camera system to further improve the detection rate."

The NIR cameras were tuned to the snakes and appear to be more effective at night because the snake's camouflage doesn't create the same glare it does in the sunlight.

Renshaw joined UCF in 2015. He has a doctorate in applied physics and a master's degree in electrical engineering from the University of Michigan. He also has a bachelor's degree in engineering physics from Cornell University. He leads the Thin-Film Optoelectronics (TFO) Lab, which conducts research and development on materials, components, and technologies for imaging systems.

Researchers remain perplexed as to what causes dementia and how to treat and reverse the cognitive decline seen in patients. In a first-of-its-kind study, researchers at the Medical University of South Carolina (MUSC) and Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School discovered that cis P-tau, a toxic, non-degradable version of a healthy brain protein, is an early marker of vascular dementia (VaD) and Alzheimer's disease (AD). Their results, published on June 2 in Science Translational Medicine, define the molecular mechanism that causes an accumulation of this toxic protein. Furthermore, they showed that a monoclonal antibody (mAb) that targets this toxic protein was able to prevent disease pathology and memory loss in AD- and VaD-like preclinical models. Additionally, this treatment was even capable of reversing cognitive impairment in an AD-like preclinical model.

"We believe our findings have not only discovered cis P-tau as a previously unrecognized major early driver of VaD and AD but also identified a highly effective and specific immunotherapy to target this common disease driver for treating and preventing AD and VaD at early stages," said Onder Albayram, Ph.D., co-lead author and assistant professor in the Division of Cardiology in the Department of Medicine at MUSC.

Aging is a normal part of life - we experience weakening of our bones and muscles, stiffening of our blood vessels and some memory lapses. But for around 50 million people worldwide, these memory lapses become progressively more severe, ultimately leading to a diagnosis of dementia.

Dementia is an umbrella term that covers AD, which accounts for 60% to 80% of cases; VaD, the second most common cause; and other less common pathologies. Currently, there are no effective treatments for AD. Interestingly, most AD cases have a vascular component, suggesting a broader relationship between cognitive function and healthy brain vasculature. A better understanding of that relationship could provide a platform to discover novel therapeutic targets.

"Our work provides evidence that cis P-tau may be a pathogenic factor that explains VaD, which is not generally linked to other dementias," added Chenxi Qiu, Ph.D., co-lead author and a postdoctoral research fellow at BIDMC, Harvard Medical School.

In a preclinical model of VaD, young mice showed signs of brain inflammation and memory loss within one month. However, treating these mice with the cis P-tau mAb prevented neural degradation and cognitive decline out to six months. In a separate preclinical model of AD, old mice showed severe cognitive impairment. Excitingly, this severe impairment was significantly reversed when mice were given the cis P-tau mAb.

"These data show that cis P-tau could be an early upstream pathogenic factor common to both diseases," said Albayram.

Translating information gained from preclinical models to humans is often difficult, but this study offers reasons to be optimistic. Accumulation of cis P-tau caused dramatic changes in the genetic architecture of affected cells in a VaD model; these changes were consistent with those seen in human AD patients. The researchers went on to show that treatment with the cis P-tau mAb reversed 85% to 90 % of those changes suggesting the power of this potential therapy.

"The genomic landscape really adapts after the silencing of this toxic protein," said Albayram. "That was a big discovery."

Not only are Albayram and Qiu excited about these findings, but colleagues at MUSC are already quite enthusiastic about this work.

"I can go on and on about this paper," said Adviye Ergul, M.D., Ph.D., professor in the College of Medicine, Department of Pathology and Laboratory Medicine at MUSC. "They provide robust evidence that there is accumulation of a specific form of the tau protein - cis P-tau - that highlights a different tau protein pathology in VaD research."

This groundbreaking research has opened the door for new potential immunotherapies and highlighted several new areas of research that need to be explored. While the researchers delineated a pathway that leads to the accumulation of cis P-tau, the underlying linkage between vascular abnormalities and activation of the pathway needs to be identified. A better understanding of how toxic cis P-tau interacts with the healthy trans P-tau could provide further insights into the progression of AD disease.

AD and VaD might not be the only diseases affected by high levels of cis P-tau. Other brain disorders with a vascular component might also arise from this toxic protein, but further study will be required to establish such a link.

"Cis P-tau may be a common, early and pathogenic factor underlying traumatic brain injury, VaD and AD," said Qiu.

As we get older and our memory begins to lapse - misplacing our car keys or forgetting the name of a new acquaintance - we fear the possibility that these are the first signs of dementia. And while there is currently no approved treatment to reverse the physiological effects of dementia, this new research may provide hope that new therapies are around the corner.

WACO, Texas (June 9, 2021) - Most people listen to music throughout their day and often near bedtime to wind down. But can that actually cause your sleep to suffer? When sleep researcher Michael Scullin, Ph.D., associate professor of psychology and neuroscience at Baylor University, realized he was waking in the middle of the night with a song stuck in his head, he saw an opportunity to study how music -- and particularly stuck songs -- might affect sleep patterns.

Scullin's recent study, published in Psychological Science, investigated the relationship between music listening and sleep, focusing on a rarely-explored mechanism: involuntary musical imagery, or "earworms," when a song or tune replays over and over in a person's mind. These commonly happen while awake, but Scullin found that they also can happen while trying to sleep.

"Our brains continue to process music even when none is playing, including apparently while we are asleep," Scullin said. "Everyone knows that music listening feels good. Adolescents and young adults routinely listen to music near bedtime. But sometimes you can have too much of a good thing. The more you listen to music, the more likely you are to catch an earworm that won't go away at bedtime. When that happens, chances are your sleep is going to suffer."

People who experience earworms regularly at night -- one or more times per week -- are six times as likely to have poor sleep quality compared to people who rarely experience earworms. Surprisingly, the study found that some instrumental music is more likely to lead to earworms and disrupt sleep quality than lyrical music.

The study involved a survey and a laboratory experiment. The survey involved 209 participants who completed a series of surveys on sleep quality, music listening habits and earworm frequency, including how often they experienced an earworm while trying to fall asleep, waking up in the middle of the night and immediately upon waking in the morning.

In the experimental study, 50 participants were brought into Scullin's Sleep Neuroscience and Cognition Laboratory at Baylor, where the research team attempted to induce earworms to determine how it affected sleep quality. Polysomnography -- a comprehensive test and the gold standard measurement for sleep -- was used to record the participants' brain waves, heart rate, breathing and more while they slept.

"Before bedtime, we played three popular and catchy songs -- Taylor Swift's 'Shake It Off,' Carly Rae Jepsen's 'Call Me Maybe' and Journey's 'Don't Stop Believin'," Scullin said. "We randomly assigned participants to listen to the original versions of those songs or the de-lyricized instrumental versions of the songs. Participants responded whether and when they experienced an earworm. Then we analyzed whether that impacted their nighttime sleep physiology. People who caught an earworm had greater difficulty falling asleep, more nighttime awakenings, and spent more time in light stages of sleep."

Additionally, EEG readings -- records of electrical activity in the brain -- from the experimental study were quantitatively analyzed to examine physiological markers of sleep-dependent memory consolidation. Memory consolidation is the process by which temporary memories are spontaneously reactived during sleep and transformed into a more long-term form.

"We thought that people would have earworms at bedtime when they were trying to fall asleep, but we certainly didn't know that people would report regularly waking up from sleep with an earworm. But we saw that in both the survey and experimental study," he said.

Participants who had a sleep earworm showed more slow oscillations during sleep, a marker of memory reactivation. The increase in slow oscillations was dominant over the region corresponding to the primary auditory cortex which is implicated in earworm processing when people are awake.

"Almost everyone thought music improves their sleep, but we found those who listened to more music slept worse," Scullin said. "What was really surprising was that instrumental music led to worse sleep quality -- instrumental music leads to about twice as many earworms."

The study found that individuals with greater music listening habits experienced persistent earworms and a decline in sleep quality. These results are contrary to the idea of music as a hypnotic that might help sleep. Health organizations commonly recommend listening to quiet music before bedtime -- recommendations that largely arise from self-reported studies. Instead, Scullin has objectively measured that the sleeping brain continues to process music for several hours, even after the music stops.

Knowing that earworms negatively affect sleep, Scullin recommends first trying to moderate music listening or taking occasional breaks if bothered by earworms. Timing of music also is important -- try to avoid it before bed.

"If you commonly pair listening to music while being in bed, then you'll have that association where being in that context might trigger an earworm even when you're not listening to music, such as when you're trying to fall asleep," he said.

Another way to get rid of an earworm is to engage in cognitive activity -- fully focusing on a task, problem or activity helps to distract your brain from earworms. Near bedtime, rather than engaging in a demanding activity or something that would disrupt your sleep, like watching TV or playing video games, Scullin suggests spending five to 10 minutes writing out a to-do list and putting thoughts to paper. A previous study by Scullin -- partially funded by a National Institutes of Health grant and the Sleep Research Society Foundation -- found that participants who took five minutes to write down upcoming tasks before bed helped "offload" those worrying thoughts about the future and led to faster sleep.

June 10, 2021, CLEVELAND: A new Cleveland Clinic-led study has identified mechanisms by which COVID-19 can lead to Alzheimer's disease-like dementia. The findings, published in Alzheimer's Research & Therapy, indicate an overlap between COVID-19 and brain changes common in Alzheimer's, and may help inform risk management and therapeutic strategies for COVID-19-associated cognitive impairment.

Reports of neurological complications in COVID-19 patients and "long-hauler" patients whose symptoms persist after the infection clears are becoming more common, suggesting that SARS-CoV-2 (the virus that causes COVID-19) may have lasting effects on brain function. However, it is not yet well understood how the virus leads to neurological issues.

"While some studies suggest that SARS-CoV-2 infects brain cells directly, others found no evidence of the virus in the brain," says Feixiong Cheng, Ph.D., assistant staff in Cleveland Clinic's Genomic Medicine Institute and lead author on the study. "Identifying how COVID-19 and neurological problems are linked will be critical for developing effective preventive and therapeutic strategies to address the surge in neurocognitive impairments that we expect to see in the near future."

In the study, the researchers harnessed artificial intelligence using existing datasets of patients with Alzheimer's and COVID-19. They measured the proximity between SARS-CoV-2 host genes/proteins and those associated with several neurological diseases where closer proximity suggests related or shared disease pathways. The researchers also analyzed the genetic factors that enabled SARS-COV-2 to infect brain tissues and cells.

While researchers found little evidence that the virus targets the brain directly, they discovered close network relationships between the virus and genes/proteins associated with several neurological diseases, most notably Alzheimer's, pointing to pathways by which COVID-19 could lead to Alzheimer’s disease-like dementia. To explore this further, they investigated potential associations between COVID-19 and neuroinflammation and brain microvascular injury, which are both hallmarks of Alzheimer's.

"We discovered that SARS-CoV-2 infection significantly altered Alzheimer's markers implicated in brain inflammation and that certain viral entry factors are highly expressed in cells in the blood-brain barrier," explained Dr. Cheng. "These findings indicate that the virus may impact several genes or pathways involved in neuroinflammation and brain microvascular injury, which could lead to Alzehimer's disease-like cognitive impairment."

The researchers also found that individuals with the allele APOE E4/E4, the greatest genetic risk factor for Alzheimer's, had decreased expression of antiviral defense genes, which could make these patients more susceptible to COVID-19.

"Ultimately, we hope to have paved the way for research that leads to testable and measurable biomarkers that can identify patients at the highest risk for neurological complications with COVID-19," said Dr. Cheng.

Dr. Cheng and his team are now working to identify actionable biomarkers and new therapeutic targets for COVID-19-associated neurological issues in COVID long-haulers using cutting-edge network medicine and artificial intelligence technologies.