Brain

It has been nearly two decades since the American College of Medical Genetics and Genomics (ACMG), together with the American College of Obstetricians and Gynecologists, made the landmark recommendation that cystic fibrosis (CF) become the first target of pan-ethnic universal carrier screening, with ACMG identifying a core panel of 23 pathogenic variants to be tested. Now, with the widespread availability and decreased cost of next-generation sequencing, it is possible to more easily interrogate all regions of the CFTR gene and correlate variants with phenotypes. This ability to move beyond targeted molecular testing methods for routine CF screening and diagnosis led to the ACMG Laboratory Quality Assurance Committee's release of a new key document: "CFTR Variant Testing: A Technical Standard of the American College of Medical Genetics and Genomics (ACMG)," published in ACMG's official journal, Genetics in Medicine.

This technical standard includes revised information about CF and the CFTR gene, new testing considerations and methodologies, and updated recommendations for the interpretation and reporting of test results. Written in clearly delineated sections, this important new resource will become a well-used reference by molecular genetics laboratories everywhere.

"Now that CF screening and diagnosis are established tests and next-generation sequencing is an established method in many clinical genetics laboratories, the ACMG wanted to update its technical laboratory standards for CFTR variant testing so that they would not only better reflect current laboratory practices but would also better enable future advancements in the field," said lead author Josh Deignan, PhD, FACMG. "Though it wasn't originally planned, it seems appropriate to have these updated ACMG standards published in May since May is also National Cystic Fibrosis Awareness Month."

The new ACMG document includes detailed sections on What to Test, How to Test and What to Report regarding CFTR variant testing.

Light detection and ranging (LiDAR) comprised an array of techniques using laser light to measure distances by multiplying the time delay between transmitted and received optical signals with the speed of light. Modern 3D LiDAR sensors combine high lateral/vertical and radial resolution, and are key components in the ongoing revolution of level 4 and 5 self-driving cars.

The prominence of 3D LiDAR sensing has its roots in 2007 DARPA autonomous driving challenge with the introduction of the first Velodyne spinning laser array sensors measuring up to 128 laser lines in parallel. Most modern LiDAR sensors rely on the time-of-flight operation principle where short pulses or pulse patterns are emitted from the sensor aperture and the power of back-reflected light is detected using a square-law photodetector.

A different principle is that of coherent laser ranging, most importantly frequency-modulated continuous wave (FMCW) LiDAR, where the laser is set up to emit linear optical frequency chirps. Heterodyne mixing with a replica of the emitted laser light maps the target distance to a radiofrequency.

Coherent detection has many inherent advantages such as enhanced distance resolution, direct velocity detection via the Doppler effect, and imperviousness to sunlight glare and interference. But the technical complexity of precisely controlling narrow-linewidth frequency-agile lasers has so far prevented the successful parallelization of FMCW LiDAR.

Now, researchers at the lab of Tobias Kippenberg at EPFL have found a new way to implement a parallel FMCW LiDAR engine by using integrated nonlinear photonic circuitry. They coupled a single FMCW laser into a silicon-nitride planar microresonator, where the continuous wave laser light is converted into a stable optical pulse train due to the double balance of dispersion, nonlinearity, cavity pumping and loss.

The study has been published in Nature.

"Surprisingly, the formation of the dissipative Kerr soliton, does not only persist when the pump laser is chirped, but transfers the chirp faithfully to all the generated comb teeth," says Johann Riemensberger, postdoc at Kippenberg's lab and first author of the study.

The small size of the microresonator means that the comb teeth are spaced 100 GHz apart, which is enough to separate them using standard diffraction optics. Because each comb tooth inherits the linear chirping of the pump laser, it was possible to create up to 30 independent FMCW LiDAR channels in the microresonator.

Each channel is capable to measure distance and velocity of a target simultaneously, while the spectral separation of the different channels makes the device immune to channel crosstalk, as well as a natural fit for co-integration with recently deployed optical phased arrays based on photonic integrated optical grating emitters.

The spatial separation of emitted beams and operation in the 1550 nm-wavelength band relaxes otherwise stringent eye and camera safety limitations. "The technology developed here at EPFL could improve acquisition rates of coherent FMCW LiDAR tenfold in the near future," says Anton Lukashchuk, PhD student in Kippenberg's lab.

The concept relies on high-quality silicon-nitride microresonsators with record-low losses amongst planar nonlinear waveguide platforms, which were produced at EPFL's Centre of MicroNanotechnology (CMi). The silicon-nitride microresonators are already commercially available by EPFL spinoff LiGENTEC SA that has specialized on fabrication of silicon nitride-based photonic integrated circuits (PIC).

This work paves a way for the widespread application of coherent LiDAR in autonomous vehicle applications in the future. The researchers are now focused on heterogeneous co-integration of laser, low-loss nonlinear microresonators, and photodetectors in a single and compact photonic package.

Due to the improvement and increased use of geochemical fingerprinting techniques during the last 25 years, the archaeological compositional data of stone tools has grown exponentially. The Pofatu Database is a large-scale collaborative project that enables curation and data sharing. The database also provides instrumental details, analytical procedures and reference standards used for calibration purposes or quality control. Thus, Pofatu ensures reproducibility and comparability between provenance studies.

Provenance studies (documenting where artefacts are found relative to their sources or place of manufacture) help archaeologists understand the "life-histories" of artefacts, in this case, stone tools. They show where the raw material come from and how artefacts were manufactured and distributed between individuals and groups. Reliable data allows scientists to reconstruct technological, economic, and social behaviors of human societies over many thousands of years.

To facilitate access to this growing body of geochemical data, Aymeric Hermann and Robert Forkel of the Department for Linguistic and Cultural Evolution, Max Planck Institute for the Science of Human History, conceived and designed Pofatu, the first open-access database of geochemical compositions and contextual information for archaeological sources and artefacts in a form readily accessible to the scientific community.

Reconstructing ancient strategies of raw material and artefact procurement

Geochemical "fingerprinting" of artefacts is the most effective way to reconstruct how and where ancient peoples extracted, transformed, and exchanged stone materials and artefacts. These fingerprints also serve as clues to understand a number of phenomenon in past human societies, such as technical and economic behaviors, as well as sociopolitical organizations.

The Pofatu Database provides researchers with access to an ever-expanding dataset and facilitates comparability and reproducibility in provenance studies. Each sample is comprehensively documented for elemental and isotopic compositions, and includes detailed archaeological provenance, as well as supporting analytical metadata, such as sampling processes, analytical procedures, and quality control.

"By providing analytical data and comprehensive archaeological details in a form that can be readily accessed by the scientific community," Hermann says, "the Pofatu Database will facilitate assigning unambiguous provenance to artefacts in future studies and will lead to more robust, large-scope modelling of long-distance voyaging and traditional exchange systems."

Additionally, Marshall Weisler, a collaborator in the Pofatu project from the University of Queensland in Australia, stated that "By tracing the transport of artefacts carried across the wide expanse of the Pacific Ocean, we will be able to reconstruct the ancient journeys enabling the greatest maritime migration in human history."

Pofatu - an operational framework for data sharing in archaeometry

Pofatu's structure was designed by Forkel and Hermann. Hermann compiled and described the data with contributions and validations by colleagues and co-authors from universities and research institutions in New Zealand, Australia, and the USA. The database uses GitHub for open-source storage and version control and common non-proprietary file formats (CSV) to enable transparency and built-in reproducibility for future studies of prehistoric exchange. The database currently contains 7759 individual samples from archaeological sites and geological sources across the Pacific Islands, but Pofatu is made for even more, Hermann notes.

"With Pofatu we activated an operational framework for data sharing in archaeometry. The database is currently focused on sites and collections from the Pacific Islands, but we welcome all contributions of geochemical data on archaeological material, regardless of geographic or chrono-cultural boundaries. Our vision is an inclusive and collaborative data resource that will hopefully continue to develop with more datasets from the Pacific as well as from other regions. The ultimate goal is a more global project contemporary to other existing online repositories for geological materials."

Although the Pofatu Database is meant to be used primarily by archaeologists, analyses of geological samples and raw material extracted from prehistoric quarries could also be used by geologists to gather essential information on the smaller or more remote Pacific islands, which are among the least studied places on the planet and sometimes lack geochemical documentation. In that sense, Pofatu is a tool that will facilitate interdisciplinary research.

New images reveal the earliest impairments to nonhuman primate fetal brain development due to alcohol ingested by the mother, in a study led by scientists at Oregon Health & Science University involving rhesus macaques.

Magnetic resonance imaging showed impairments to brain growth during the third trimester of pregnancy, even though the fetus was exposed to alcohol only during the first trimester.

The research, published in the Proceedings of the National Academy of Sciences, highlights the danger of binge drinking early in a pregnancy, even before a woman realizes she's pregnant. It also suggests the potential benefit of using in-utero imaging to detect signs of fetal-alcohol syndrome before birth.

"The earlier the detection, the better," said senior author Chris Kroenke, Ph.D., associate professor in the Division of Neuroscience at the Oregon National Primate Research Center at OHSU. "Predicting risks for specific impairments means that therapy can start soon after the baby is born, when the brain has the greatest plasticity."

The study builds upon recent advancements in the quality and resolution of magnetic resonance imaging methods used to examine the fetal brain in utero.

"The goal of this study was to assess the sensitivity of this common clinical diagnostic to detect the impact of drinking binge level intakes of alcohol [4-6 drinks] early in pregnancy to model patterns of drinking in women before they know they are pregnant," said co-author Kathleen Grant, Ph.D., professor and chief of the Division of Neuroscience at the primate center.

Researchers at the primate center monitored a total of 28 pregnant macaques, measuring brain development through MRIs at three stages of pregnancy. In an experiment that would not be possible to conduct in people, half of the macaques consumed the daily human equivalent of six alcoholic drinks per day while the rest consumed no alcohol.

Imaging during the course of the pregnancy revealed a difference in fetal brain development by the 135th day of a 168-day gestational term, at the beginning of the third trimester. Imaging revealed no difference with the control group measured during the second trimester.

Electrophysiological recordings of the brains following MRI suggested the differences are functionally significant. Aside from validating the potential usefulness as an early diagnostic tool for fetal alcohol syndrome, researchers say the images generated during the study were of high enough quality that they expect it to be useful as a point of comparison for other scientists working in the field.

"The brain atlases described in our paper have been uploaded to a website where other researchers can access it," Kroenke said.

An imbalance of unstable molecular species called 'free radicals' will change the colour of cells - and a new imaging technique could one day allow scientists to detect and decode this colour without needing to take samples from the body, a new study by UNSW Sydney researchers has found.

The paper was published online yesterday in Redox Biology.

"In our study of cell cultures and tissues in the lab, we found that colour is like a thermometer for oxidative stress," says UNSW Engineering Professor Ewa Goldys, lead author of the study and Deputy Director of the ARC Centre of Excellence for Nanoscale Biophotonics.

Oxidative stress is caused by an overabundance of free radicals, which can cause damage to cells, DNA and proteins if left unchecked. Poor diet, alcohol consumption and obesity are some factors that can lead to the overproduction of free radicals.

Our body has a natural system for balancing these free radicals with antioxidants, but too many free radicals will make it harder for the body to repair damaged cells. Oxidative stress can cause chronic inflammation and is linked to many diseases, such as heart disease, diabetes and cancer.

"Oxidative stress isn't disease-specific, but its restoration to healthy levels is an excellent measure of how well a therapeutic approach is working," says Prof Goldys.

Despite the important role of oxidative stress to our health, it is often overlooked in medical diagnostics. This is largely because it's difficult to measure on cells 'in-vivo' - within the body.

Current methods for testing oxidative stress involve extracting cells from the body and testing their response in a lab. While some cells can be easily removed, such as blood, this method isn't an option for other parts of the body.

To solve this problem, Prof Goldys and her team adapted a standard fluorescent microscope - a microscope that detects natural fluorescent emissions from cells - to test whether cell and tissue colour is impacted by oxidative stress. They also developed a UV-free version of this technology for instances when UV is too dangerous to use, like in ophthalmology and reproductive health.

The microscopic camera works by emitting bursts of low-level LED light at various wavelengths onto cells and tissues. The light is absorbed by fluorescent molecules, which then emit their own light in response.

This fluorescent light allows the researchers to capture detailed maps of cells and tissues via a series of photographs. The microscope then decodes what the colours mean at a molecular level.

"The microscope has a device that precisely captures the colours in the cells," explains Prof Goldys.

"We then use a big data approach to digitally 'unmix' the colour into its molecular components - red, green and blue, for example."

The team developed a way to quantify each colour component by assigning it with a value. Once these values are tallied, scientists can measure oxidisation levels without need for cell extraction and analytical procedures.

"Once you have numbers, you can test all sorts of things," says Prof Goldys, who was awarded a prestigious Eureka Award in 2016 for her discovery that the colours of cells and tissues can be subtle indicators of health and disease.

While their adapted microscope is not yet on the market, Prof Goldys is undertaking steps to begin the clinical trial in two years' time. First, she will conduct an animal study, then seek TGA approval for the adapted microscope to be used in human studies, before starting a human trial in a selected disease condition.

If these steps are successful, the adapted microscope could become a common tool used in medical practices and scientific research.

In the meantime, Prof Goldys is excited about her next project, which will focus on how this technology can help monitor eye disease - particularly glaucoma.

Alongside researchers including UNSW Scientia Fellow Dr Nicole Carnt, the team are developing a bespoke camera that will photograph the back of the eye via the pupil. This camera will help ophthalmologists measure the oxidative stress of cells and tissues in the retina.

"The findings could change how we monitor and treat eye diseases," says Prof Goldys.

"Early detection could hopefully help medical staff and patients slow disease progression."

Social and community disruptions caused by the COVID-19 restrictions could have a lasting effect on child wellbeing, Flinders University researchers warn.

While health, safety and education responses are the focus of restrictions, the needs of childhood independence, self-determination and play are less acknowledged, Flinders University experts explain in a new publication.

"Play is a key aspect of children's wellbeing from their perspectives," says lead author Jennifer Fane. "The closure of playgrounds, schools and the fear and worry associated with being in public spaces has likely had significant impacts on children during this time.

"As children return to school, and life starts to resume as it did pre-COVID-19, focus and attention to children's opportunities for play - and their ability to exercise reasonable 'agency' during this time of significant transition - are two key aspects that can support their wellbeing during this difficult time."

While everyone's freedoms have been impacted by COVID-19 pandemic, children's agency, or ability to make choices and decisions within adult-imposed constraints, has never been more apparent.

"Young children interviewed in the study told us of the importance to their lives of trying new things and having a say about play," says Flinders Professor of Public Health Colin MacDougall, a co-author on the Child Indicators Research paper.

"As the world takes baby steps to ease these life-saving restrictions, and move into an uncertain future, we must take the time to think about very young children.

"This research can be used to help chart a course for the multiple transitions these children are undergoing."

Ms Fane, whose PhD at Flinders focused on communicating with preschoolers, says these perspectives can support child wellbeing in future, including as government restrictions on people's boundaries affects where children play and how much they can have a say.

PHOENIX (May 12, 2020) - Children and young adult burn survivors are more troubled by staring, bullying, and uncomfortable questions than the actual physical discomfort and memories of their accidents, according to research that was selected to be presented at the American Burn Association's Annual Meeting and published in the Journal of Burn Care & Research. While treatment is typically focused primarily on acute care for physical wounds, the surveys suggest that survivors are left with few tools to handle social anxieties and traumatizing memories.

"Over the years, we have made many advancements in treating the physical wounds of burn survivors, but more needs to be done to treat the social and emotional wounds that come from these injuries," said Ruth Rimmer, PhD, CLCP, volunteer and former director of psychosocial research for the Arizona Burn Center at Valleywise Health in Phoenix. "Our research shows that the most difficult issue that children and young adult survivors deal with is the reaction they get from other people. Giving them the tools to handle these interactions is critical to their well-being."

The findings come from two studies that asked more than 200 young adult (17-25 years old) and child (10-16 years old) burn survivors to reflect on the key challenges they faced while recovering and growing up.

In the first study, 64 young adults were asked to respond to the statement: "The hardest thing about being burned is..." Their reactions identified seven primary themes common to burn survivors:

People staring

Being bullied

Memories of being burned

Needing additional surgeries

Self-consciousness about scars

Getting unwanted questions about burns

Pain and itching

In the second study, 147 child burn survivors and 81 young adult survivors were asked to rate the level of difficulty they experienced for each of those seven themes on a four-point scale. More than 70% of respondents said they were bothered by staring and bullying, with 72% identifying bullying as the most painful reaction, and 71% identifying staring. More than half of respondents reported issues with scars (65%), memories of being burned (52%) and pain and itching (50%). Girls were bothered significantly more than boys by their scars.

The top mean scores for child burn survivors on the four-point scale included: Remembering the Burn (61%) & Getting Unwanted Questions (61%). Some significant differences emerged between the two age groups. Child burn survivors were more likely than young adults to report being troubled by "Getting Unwanted Questions," (61% vs. 43%) while the young adults were significantly more likely than child burn survivors to report pain from "Being Bullied" (63% vs. 46%).

"While both groups of survivors have to cope with unwanted stares and comments, it's interesting that bullying seems to be less of a problem for survivors today than a few years ago," said Rimmer. "This suggests that there may be a shift in how child burn survivors are treated by their peers and that bullying programs in schools should be supported and perhaps expanded."

As a result of these findings, the researchers suggest that burn units should incorporate supportive strategies, such as psychological or social interventions such as burn camp to complement surgical and medical treatments. By providing survivors with constructive coping strategies, the researchers suggest that it will help to improve burn-injured youth's social interactions and overall quality of life.

Earth may have been far more oxygen-rich early in its history than previously thought, setting the stage for the evolution of complex life, according to new research by scientists at the University of Alberta and the University of Tartu in Estonia. The study provides evidence for elevated oxygen levels 2 billion years ago and flies in the face of previously accepted models.

The international team of researchers, led by UAlberta scientists, studied a Russian drill core containing shungite--a unique carbon-rich sedimentary rock deposited 2 billion years ago. The material provides several clues about oxygen concentrations on Earth's surface at that time, including strikingly high levels of molybdenum, uranium, and rhenium, as well as elevated uranium isotope ratios.

"These trace metals are only thought to be common in Earth's oceans and sediments when oxygen is abundant," explained Kaarel Mänd, a PhD candidate in the University of Alberta's Department of Earth and Atmospheric Sciences and lead author of the study. "These trace metal concentrations are unrivaled in early Earth's history, suggesting elevated levels of oxygen at the time when the shungite was deposited."

What's puzzling, Mänd explained, is that many widely accepted models of Earth's carbon and oxygen cycles predict that shungite should have been deposited at a time of rapid decrease in oxygen levels.

"What we found contradicts the prevailing view," says Mänd, who is completing his PhD under the supervision of Professor Kurt Konhauser. "This will force the Earth science community to rethink what drove the carbon and oxygen cycles on the early Earth."

The new findings also provide insight into the evolution of complex life. Earth's "middle age" represents the backdrop for the appearance of eukaryotes. Eukaryotes are the precursors to all complex life, and require high oxygen levels in their environment to thrive. This study strengthens the idea that suitable conditions for the evolution of complex life on early Earth began much earlier than previously thought.

Future research will examine the delay between the initial rise of oxygen and the appearance and spread of eukaryotes, remaining an area of active research, one that University of Alberta and University of Tartu researchers are well positioned to help answer.

Once upon a time, the Three Kings brought precious gifts to the new-born baby Jesus: as well as gold and myrrh, they also had frankincense in their bags. "Even today, frankincense is a valuable gift," says Prof. Oliver Werz of Friedrich Schiller University - although he is not really thinking about the biblical meaning of frankincense. "The resin extracted from the bark of the frankincense tree contains anti-inflammatory substances, which make it suitable for the treatment of diseases such as asthma, rheumatoid arthritis or neurodermatitis, among others," he explains.

Pharmacist Werz and his team have been investigating the anti-inflammatory effect of frankincense resin and its components for several years. Now, together with colleagues in the US, the Jena University researchers have succeeded in uncovering the molecular mechanism of boswellic acid, a substance which is responsible for the anti-inflammatory effect of frankincense. They present their results in the current issue of the specialist journal "Natural Chemical Biology" (DOI: 10.1038/s41589-020-0544-7).

Crystal structure analyses reveal where active substances target the inflammatory enzyme

The enzyme 5-lipoxygenase plays a key role in the effect of frankincense. "It has been known for more than 40 years that this enzyme promotes the formation of leukotrienes, an important group of inflammatory mediators in the human body," explains Werz. However, in its current paper, the research team has for the first time been able to clarify and image the crystal structure of this central inflammatory enzyme with bound inhibitors. The images of the crystal structure allow detailed studies of the enzyme and its interaction with active substances, as well as the development of new anti-inflammatory drugs.

And that is exactly what Werz and his colleagues have done. In addition to zileuton, an anti-inflammatory drug already on the market, which is a synthetic preparation used to treat asthma, the researchers have combined the enzyme with various natural products and analysed the crystal structures of the resulting complexes. The result initially surprised the researchers: while other natural products, in a similar way to zileuton, dock directly to the active site of the enzyme and thus inhibit its function, boswellic acid binds to another site of the enzyme molecule, far from the active site. "However, this binding leads to structural changes in the active site and this also inhibits the enzyme activity," says Werz.

Domino effect in the enzyme structure

Therefore, these structural changes triggered by the frankincense component already have an anti-inflammatory effect. "But the influence of boswellic acid goes far beyond this," says Dr Jana Gerstmeier. The pharmacist from Werz's team is one of the study's two lead authors. "This binding creates a domino effect, which also causes a change in the specificity of the enzyme," Gerstmeier adds. Instead of catalysing the synthesis of pro-inflammatory leukotrienes, 5-lipoxygenase produces anti-inflammatory substances under the influence of boswellic acid. "That means, in simple terms, that the frankincense component reprograms the inflammatory enzyme into an anti-inflammatory enzyme."

According to the authors of the study, these findings can now be used on the one hand to test the boswellic acids from frankincense in relevant disease models and perhaps later to develop them as a drug to treat inflammatory diseases. On the other hand, thanks to the newly discovered binding site on 5-lipoxygenase, other potential drugs can be developed and their effectiveness as anti-inflammatory agents tested in experiments.

Questions about the genealogical imprint of tumors have hovered over cancer research since the completion of the Human Genome Project in 2003. Is liver cancer different at a basic, molecular level in people of African descent than people of European descent? Does breast cancer have a different genetic profile in East Asians than Native Americans?

A new paper by researchers from the NCI Cancer Genome Analysis Network, a collaborative group with investigators in the U.S., Canada and Europe, provides the most comprehensive look to date at the effect of ancestry on the molecular makeup of normal and cancerous tissues. Drawing on data from The Cancer Genome Atlas (TCGA) involving 10,678 patients and 33 cancer types, the investigators found that ancestry was tied to variations in hundreds of genes, but that the most important of these differences were linked to specific tissue types. The study is being published online today by Cancer Cell.

"We found that in patients of different ancestries, the molecular features corresponding to those differences were largely confined to specific organs and tissue types," said Rameen Beroukhim, MD, PhD, of Dana-Farber and the Broad Institute, the co-senior author of the study with Andrew Cherniack, PhD, group leader at Dana-Farber and the Broad Institute. "This suggests that tracking the molecular effects of ancestry - both in normal and cancer tissue - needs to take a tissue-by-tissue approach."

Among the researchers' specific findings:

From a molecular standpoint, people of African ancestry tend to have a different type of kidney cancer than people of European ancestry. The African variety is marked less often by mutations that disable the VHL gene, spurring the growth of new blood vessels for tumors.

Bladder cancers in people of East Asian extraction show fewer signs of drawing an immune system response than bladder tumors in people of European background.

In the study, investigators used a variety of molecular techniques to determine the ancestry of the patients whose tissue samples were analyzed. Patients were classified as being primarily of European, East Asian, African, Native/Latin American, or South Asian descent. Patients whose ancestry was at least 20% mixed were classified as being of admixed descent. (These patients were subcategorized by their primary ancestry, such as African-Admixed, European-Admixed, etc.) As a group, the patients had 33 cancer types, 13 of which were further divided into subtypes.

TCGA had conducted a deep analysis of each patient's tissue, testing cancerous and normal cells for a range of molecular features. These included mutations (miscopied sections of DNA); patterns of DNA methylation (a process that influences whether genes are switched on or off); messenger RNA (a molecule that carries a transcribed version of DNA and is indicative of gene activity); and microRNA (a form of RNA that assists or hampers gene activity). The NCI Cancer Genome Analysis Network investigators used this data to see whether differences in any of these features reflected differences in ancestry.

"We found that ancestry-associated differences spanned all of these features and were present in hundreds of different genes," Cherniack stated. "It turned out, though, that the most significant differences - the ones that affect how cells function and interact with the rest of the body - were profoundly tissue-specific." Although ancestry affected molecular features in most cancer types, these effects were not shared across cancer types. Molecular differences in lung cancers that were traceable to African ancestry, for example, were not found in breast, pancreatic, or other cancers.

The data also enabled investigators to ask whether the ancestry-related features of normal cells carried over into the cancerous versions of those cells - whether the molecular particularities of lung cells in people of European extraction for example, are also found in the lung cancer cells of such individuals. They found that this was overwhelmingly the case. "Most of the differences in the normal tissues of people with specific ancestries are recapitulated in cancer," Beroukhim stated. Moreover, evidence suggests that some of these differences may contribute to the development of certain cancers in people with similar backgrounds.

Having access to data from patients of mixed lineage proved to be an asset, the study authors say. Investigators conducted their initial analysis in patients whose ancestry was at least 80% within one of the five genealogical groups. They followed this with a similar analysis of data from the admixed populations. "When the results of the two analyses jibed - when molecular differences specific to one ancestral group also appear in patients whose ancestry is a combination of that group and others - it was particularly strong evidence of the validity of the original finding." said one of the study's co-lead authors, Jian Carrot-Zhang, PhD, postdoctoral research fellow of the Meyerson group at Dana-Farber and the Broad. "The patients of mixed background were a particularly powerful group in which to study the molecular effects of ancestry in cancer," Beroukhim stated. "It helped us narrow down which regions of the genome contribute to these differences."

The comprehensive nature of the study revealed some of the shortcomings of previous efforts to link ethnicity and ancestry to molecular elements of cells. For one, such studies tended to lump various subtypes of cancer together, Beroukhim said, despite the fact that certain subtypes are more common in certain ancestries than others. Some of the techniques used to dissect molecular features may also have skewed the results of previous studies.

Researchers have yet to determine whether the molecular differences between ancestries result from environmental factors or genetic factors. However, they did identify genetic differences between ancestries that could explain many of their findings.

"Our findings point to a need for more samples from diverse ancestries to conduct a truly comprehensive ancestry analysis, especially of normal tissues," Beroukhim remarks. "This study represents an important step in that direction."

An international consortium of researchers have identified particular sources of prenatal stress, as experienced by mothers, that have a direct effect on a child's subsequent mental health. The findings emerged from the DREAM-BIG (Developmental Research in Environmental Adversity, Mental health, BIological susceptibility and Gender) project, and are published in the Journal of the American Academy of Child & Adolescent Psychiatry.

"We already understood that the foundations for life-long mental health are laid in the very first years of life, but we have further validated the idea that prenatal stress, the mother's psychological well-being during pregnancy, is an important factor," said Dr. Ashley Wazana, the principal investigator on DREAM-BIG and Director of the Early Childhood Disorders Day Hospital at the Jewish General Hospital. "With data to support the impact of prenatal stress, we can look at protective measures that could help mothers to insulate their babies."

The paper identifies four prenatal maternal factors. A general affective symptoms factor and three specific factors: an anxiety/depression factor, a somatic factor, and a pregnancy-specific worries factor.

The authors conclude, "The findings in this paper underscore the importance of intervening in the prenatal period, including for pregnancy-specific worries. Currently, there are few prenatal interventions to reduce maternal depression, anxiety, or stress, and even fewer studies that track the long-term effects in the offspring whose mothers receive such interventions."

As much as anxiety and stress factor into pregnancy during normal times, the on-going COVID-19 pandemic is an added stressor and, furthermore, causes mothers-to-be to adapt to social distancing provisions.

"Of course, there are multiple factors at play, including genetics,sex and gender, and the environment after birth, but when you combine maternal stress with this particular environmental adversity, you have the potential for greater mental health challenges for children who are born into this post-pandemic world," said Dr. Eszter Szekely, a postdoctoral research scholar at the Lady Davis Institute (LDI) and McGill University's Department of Psychiatry, the first author on the paper.

The general affective symptoms, which relate to the overall mood of the mother, during pregnancy are predictive of mental health problems that emerge between the ages of four and eight. Some fifty-percent of mental health disorders emerge before the age of five, while seventy-five-percent are evident before adulthood. To offer perspective on the burden of mental health problems, on a global basis, they constitute the leading cause of disability.

"We believe that mental health ought to be a fundamental part of prenatal health," said Dr. Wazana, a researcher at the LDI and Assistant Professor of Psychiatry at McGill, speaking about DREAM-BIG's concern with the earliest environment which children experience. "Pregnancy is not a cocoon and stress can be an important factor in childhood mental health. We need to appreciate the importance of mental health needs across the lifespan, starting with pregnancy. We would like to see mothers have access to prenatal mental health resources, but, unfortunately, the wait time for such services can be longer than the gestation period."

A new study from researchers at North Carolina State University suggests that a material consisting of a polymer compound embedded with bismuth trioxide particles holds tremendous potential for replacing conventional radiation shielding materials, such as lead.

The bismuth trioxide compound is lightweight, effective at shielding against ionizing radiation such as gamma rays, and can be manufactured quickly - making it a promising material for use in applications such as space exploration, medical imaging and radiation therapy.

"Traditional radiation shielding materials, like lead, are often expensive, heavy and toxic to human health and the environment," says Ge Yang, an assistant professor of nuclear engineering at NC State and corresponding author of a paper on the work. "This proof-of-concept study shows that a bismuth trioxide compound could serve as effective radiation shielding, while mitigating the drawbacks associated with traditional shielding materials."

In the new study, researchers demonstrated that they could create the compound using a curing method that relies on ultraviolet (UV) light - rather than relying on time-consuming high-temperature techniques.

"Using the UV curing method, we were able to create the compound on the order of minutes at room temperature - which holds potential for the rapid manufacturing of radiation shielding materials," Yang says. "This is an important point because thermal polymerization, a frequently used method for making polymer compounds, often relies on high temperatures and can take hours or even days to complete. The UV curing method is both faster and less expensive."

Using the UV curing method, the researchers created samples of the polymer compound that include as much as 44% bismuth trioxide by weight. The researchers then tested the samples to determine the material's mechanical properties and whether it could effectively shield against ionizing radiation.

"This is foundational work," Yang says. "We have determined that the compound is effective at shielding gamma rays, is lightweight and is strong. We are working to further optimize this technique to get the best performance from the material.

"We are excited about finding a novel radiation shielding material that works this well, is this light, and can be manufactured this quickly."

2,5-furandicarboxylic acid (FDCA), which is produced by oxidation of 5-hydroxymethylfurfural (HMF), is the crucial precursor for the production of polyethylene 2,5-furandicarboxylate to replace petroleum-derived polyethylene terephthalate. Electrochemical oxidation of HMF to FDCA is regarded as a clean and environment-friendly process since electrons drive the reaction at the cathode without extra chemical oxidants. Since abundant 3d electrons and unique eg orbitals enhance the covalency of transition metal-oxygen bonds, Ni-based catalysts have been considered as a great candidate for HMF electrocatalysis. For instance, a porous Ni-based electrocatalyst was prepared by the electrodeposition method for alcohol and hydrogen evolution reactions. Ni2P nanoparticles and porous Ni3S2 were reported as efficient electrocatalysts for HMF oxidation.

Very recently, Dr. Yuqin Zou and colleagues in Hunan University elaborately prepared a hierarchically nanostructured NiO-Co3O4 electrode with plentiful interface defects through a simple hydrothermal-annealing method. The interface effect could create rich cation vacancies, modulate the electronic properties of Co and Ni atoms, and raise the oxidation state of Ni species. As a result, the as-synthesized hierarchical NiO-Co3O4 nanosheets exhibited the excellent HMF oxidation activity and stability. Furthermore, in-situ SFG results and ex-situ HPLC were used to better understand the reactive intermediates and pathways during the HMF oxidation. The current study offers an efficient way to create cation vacancies at the interfacial sites and proves the positive role of cation vacancies on catalyzing the HMF electro-oxidation. The current study offers an efficient way to create cation vacancies and proves the positive role of cation vacancies on catalyzing the HMF electro-oxidation.

Recently, this research group also demonstrated the catalytic activity of Ni3N for HMF oxidation. Besides, NiO electrocatalysts are impressive in biomass conversion due to their low cost and simple synthetic methods. On the other hand, the interface engineering is a promising approach to modulate the electronic properties, tune the intermediate adsorption, and expose more active sites. For example, the core/shell NiO@Co3O4 nanocomposites with abundant edge sites because the interface effect shows enhanced catalytic activities for oxygen evolution reactions (OER).

A woman walking down the street hears a bang. Several moments later she discovers her boyfriend, who had been walking ahead of her, has been shot. A month later, the woman checks into the emergency room. The noises made by garbage trucks, she says, are causing panic attacks. Her brain had formed a deep, lasting connection between loud sounds and the devastating sight she witnessed.

This story, relayed by clinical psychiatrist and co-author of a new study Mohsin Ahmed, MD, PhD, is a powerful example of the brain's powerful ability to remember and connect events separated in time. And now, in that new study in mice published today in Neuron, scientists at Columbia's Zuckerman Institute have shed light on how the brain can form such enduring links.

The scientists uncovered a surprising mechanism by which the hippocampus, a brain region critical for memory, builds bridges across time: by firing off bursts of activity that seem random, but in fact make up a complex pattern that, over time, help the brain learn associations. By revealing the underlying circuitry behind associative learning, the findings lay the foundation for a better understanding of anxiety and trauma- and stressor-related disorders, such as panic and post-traumatic stress disorders, in which a seemingly neutral event can elicit a negative response.

"We know that the hippocampus is important in forms of learning that involve linking two events that happen even up to 10 to 30 seconds apart," said Attila Losonczy, MD, PhD, a principal investigator at Columbia's Mortimer B. Zuckerman Mind Brain Behavior Institute and the paper's co-senior author. "This ability is a key to survival, but the mechanisms behind it have proven elusive. With today's study in mice, we have mapped the complex calculations the brain undertakes in order to link distinct events that are separated in time."

The hippocampus -- a small, seahorse-shaped region buried deep in the brain -- is an important headquarters for learning and memory. Previous experiments in mice showed that disruption to the hippocampus leaves the animals with trouble learning to associate two events separated by tens of seconds.

"The prevailing view has been that cells in the hippocampus keep up a level of persistent activity to associate such events," said Dr. Ahmed, an assistant professor of clinical psychiatry at Columbia's Vagelos College of Physicians and Surgeons, and co-first author of today's study. "Turning these cells off would thus disrupt learning."

To test this traditional view, the researchers imaged parts of the hippocampus of mice as the animals were exposed to two different stimuli: a neutral sound followed by a small but unpleasant puff of air. A fifteen-second delay separated the two events. The scientists repeated this experiment across several trials. Over time, the mice learned to associate the tone with the soon-to-follow puff of air. Using advanced two-photon microscopy and functional calcium imaging, they recorded the activity of thousands of neurons, a type of brain cell, in the animals' hippocampus simultaneously over the course of each trial for many days.

"With this approach, we could mimic, albeit in a simpler way, the process our own brains undergo when we learn to connect two events," said Dr. Losonczy, who is also a professor of neuroscience at Columbia's Vagelos College of Physicians and Surgeons.

To make sense of the information they collected, the researchers teamed up with computational neuroscientists who develop powerful mathematical tools to analyze vast amounts of experimental data.

"We expected to see repetitive, continuous neural activity that persisted during the fifteen-second gap, an indication of the hippocampus at work linking the auditory tone and the air puff," said computational neuroscientist Stefano Fusi, PhD, a principal investigator at Columbia's Zuckerman Institute and the paper's co-senior author. "But when we began to analyze the data, we saw no such activity."

Instead, the neural activity recorded during the fifteen-second time gap was sparse. Only a small number of neurons fired, and they did so seemingly at random. This sporadic activity looked distinctly different from the continuous activity that the brain displays during other learning and memory tasks, like memorizing a phone number.

"The activity appears to come in fits and bursts at intermittent and random time periods throughout the task," said James Priestley, a doctoral candidate co-mentored by Drs. Losonczy and Fusi at Columbia's Zuckerman Institute and the paper's co-first author. "To understand activity, we had to shift the way we analyzed data and use tools designed to make sense of random processes."

Ultimately, the researchers discovered a pattern in the randomness: a style of mental computing that seems to be a remarkably efficient way that neurons store information. Instead of communicating with each other constantly, the neurons save energy -- perhaps by encoding information in the connections between cells, called synapses, rather than through the electrical activity of the cells.

"We were happy to see that the brain doesn't maintain ongoing activity over all these seconds because, metabolically, that's not the most efficient way to store information," said Dr. Fusi, who is also a professor of neuroscience at Columbia's Vagelos College of Physicians and Surgeons. "The brain seems to have a more efficient way to build this bridge, which we suspect may involve changing the strength of the synapses."

In addition to helping to map the circuitry involved in associative learning, these findings also provide a starting point to more deeply explore disorders involving dysfunctions in associative memory, such as panic and pos-ttraumatic stress disorder.

"While our study does not explicitly model the clinical syndromes of either of these disorders, it can be immensely informative," said Dr. Ahmed, who is also a member of the Losonczy lab at Columbia's Zuckerman Institute. "For example, it can help us to model some aspects of what may be happening in the brain when patients experience a fearful association between two events that would, to someone else, not elicit fright or panic."

Scientists have successfully developed a new technique to reliably grow crystals of organic soluble molecules from nanoscale droplets, unlocking the potential of accelerated new drug development.

Chemistry experts from Newcastle and Durham universities, working in collaboration with SPT Labtech, have grown the small crystals from nanoscale encapsulated droplets. Their innovative method, involving the use of inert oils to control evaporative solvent loss, has the potential to enhance the drug development pipeline.

Whilst crystallization of organic soluble molecules is a technique used by scientists all over the world, the ability to do so with such small quantities of analyte is ground-breaking.

Through the use of this new method, called Encapsulated Nanodroplet Crystallisation (ENaCt), the researchers have shown that hundreds of crystallisation experiments can be set up within a few minutes. Each experiment involves a few micrograms of molecular analyte dissolved in a few nanolitres of organic solvent and is automated, allowing for rapid set up of hundreds of unique experiments with ease. Concentration of these nanodroplet experiments results in the growth of the desired high quality single crystals that are suitable for modern X-ray diffraction analysis.

Publishing their findings in the journal Chem, the team, led by Drs Hall and Probert, of Newcastle University, UK, successfully developed a new approach to molecular crystallisation which allows access, within a few days, to high quality single crystals, whilst requiring only few milligrams of analyte.

Dr Hall, Senior Lecturer in Chemistry, Newcastle University, said: "We have developed a nanoscale crystallisation technique for organic-soluble small molecules, using high-throughput liquid-handling robotics to undertake multiple crystallisation experiments simultaneously with minimal sample requirements and high success rates.

"This new method has the potential to have far-reaching impact within the molecular sciences and beyond. Fundamental research will benefit from highly detailed characterisation of new molecules, such as natural products or complex synthetic molecules, by X-ray crystallography, whilst the development of new drugs by the pharmaceutical industry will be accelerated, through rapid access to characterised crystalline forms of new active pharmaceutical ingredients."

Understanding these new crystalline forms, known as polymorphs, is essential to the successful generation of new pharmaceutical agents and drugs. The ability to investigate these forms quickly and on a vast scale, whilst minimising the amount of analyte required, could be a key

Breakthrough enabled by the new ENaCT protocol.

Dr Paul Thaw from SPT Labtech, added: "Enabling this work to develop a novel high-throughput method for single crystal X-ray diffraction on mosquito® with the Newcastle team has been a pleasure. Having the ability to quickly screen organic soluble small molecules on the microgram scale will deliver valuable insight for both academic research and pharmaceutical drug design and validation."

Dr Probert, Senior Lecturer in Inorganic Chemistry and Head of Crystallography, Newcastle University, commented "...this new approach to crystallisation has the ability to transform the scientific landscape for the analysis of small molecules, not only in the drug discovery and delivery areas but also in the more general understanding of the crystalline solid state ..."

The whole team believe that the ENaCt methodology has the potential rewrite some of the preconceptions within the molecular sciences and beyond.