Brain

The functional ability of older people is nowadays better when it is compared to that of people at the same age three decades ago. This was observed in a study conducted at the Faculty of Sport and Health Sciences at the University of Jyväskylä, Finland. The study compared the physical and cognitive performance of people nowadays between the ages of 75 and 80 with that of the same-aged people in the 1990s.

"Performance-based measurements describe how older people manage in their daily life, and at the same time, the measurements reflect one's functional age," says the principal investigator of the study, Professor Taina Rantanen.

Among men and women between the ages of 75 and 80, muscle strength, walking speed, reaction speed, verbal fluency, reasoning and working memory are nowadays significantly better than they were in people at the same age born earlier. In lung function tests, however, differences between cohorts were not observed.

"Higher physical activity and increased body size explained the better walking speed and muscle strength among the later-born cohort," says doctoral student Kaisa Koivunen, "whereas the most important underlying factor behind the cohort differences in cognitive performance was longer education."

Postdoctoral researcher Matti Munukka continues: "The cohort of 75- and 80-year-olds born later has grown up and lived in a different world than did their counterparts born three decades ago. There have been many favourable changes. These include better nutrition and hygiene, improvements in health care and the school system, better accessibility to education and improved working life."

The results suggest that increased life expectancy is accompanied by an increased number of years lived with good functional ability in later life. The observation can be explained by slower rate-of-change with increasing age, a higher lifetime maximum in physical performance, or a combination of the two.

"This research is unique because there are only a few studies in the world that have compared performance-based maximum measures between people of the same age in different historical times," says Rantanen.

"The results suggest that our understanding of older age is old-fashioned. From an aging researcher's point of view, more years are added to midlife, and not so much to the utmost end of life. Increased life expectancy provides us with more non-disabled years, but at the same time, the last years of life comes at higher and higher ages, increasing the need for care. Among the ageing population, two simultaneous changes are happening: continuation of healthy years to higher ages and an increased number of very old people who need external care."

Late blight is the most important pathogen in potato and causes devastation worldwide. The disease, caused by the oomycete Phytophthora infestans, was the trigger of the Irish Famine and still one of the most serious threats to potato production that causes significant economic losses.

In a recent collaboration between the Chinese Academy of Agricultural Sciences and the James Hutton institute, scientists identified a diploid wild potato with a high resistance to P. infestans. They discovered novel R genes in this potato using dRenSeq analysis, and further transcriptional analysis revealed the essential role of multiple signal transduction pathways and secondary metabolic pathways in plant immunity in the wild potato.

"We found that the observed resistance in this wild potato was due to previously uncharacterized novel resistance genes," explained Guangcun Li, one of the scientists involved in the study. "We also discovered that photosynthesis was inhibited to promote the immune response."

It is a new discovery that photosynthetic inhibition exists in potatoes. However, the scientists also found that the physical barrier of leaves was very important.

"The leaves of this wild potato are hard and show immunity when inoculated with P. infestans at low concentration," said Li.

This research provides new resources for potato late blight resistance breeding and a new theoretical basis for disease resistance breeding of potato. To learn more, read "New Findings on the Resistance Mechanism of an Elite Diploid Wild Potato Species JAM1-4 in Response to a Super Race Strain of Phytophthora infestans," published in the August issue of Phytopathology.

October Issue SLAS Technology Features Cover Article, "Role of Digital Microfluidics in Enabling Access to Laboratory Automation and Making Biology Programmable"

Oak Brook, IL - The October issue of SLAS Technology features the cover article, "Role of Digital Microfl-uidics in Enabling Access to Laboratory Automation and Making Biology Programmable" by Varun B. Kothamachu, Ph.D., Sabrina Zaini and Federico Muffatto (Digi.Bio).

October's cover article explores the role of digital microfluidics (DMF) as a "digital bioconverter"" that brings together the digital aspects of the design-build-learn cycle with the physical nature of experimentation. The article also discusses the function of a DMF device and examines how DMF is limited by known technical and operational challenges and the key to overcoming these challenges.

Such challenges that face scientists are the associated costs and late-stage risk in developing microfluid technologies for the purpose of diagnosing and preventing bodily disorders, including haemostatic disorders, cancers and molecular abnormalities. New capabilities and avenues are required to provide a landscape fit for further research and development.
The latest issue includes six articles of original research, in addition to a technical brief, a methods and protocol article, and the featured cover article.

Original research articles include:

Microfluidic Pneumatic Printed Sandwiched Microdroplet Array for High-Throughput Enzymatic Reaction and Screening

Microflow-Based Device for In Vitro and Ex Vivo Drug Permeability Studies

Integration of Acoustic Liquid Handling into Quantitative Analysis of Biological Matrix Samples

Diffusion MRI-Derived per Area Vessel Density as a Surrogate Biomarker for Detecting Viral Hepatitis-B Induced Liver Fibrosis: A Proof of Concept Study

Hybrid Blood Collection Tubes: Combining the Best Attributes of Glass and Plastic for Safety and Shelf Life

A Comparative Analysis of Methods for Quantitation of Sugar during the Corn-to-Ethanol Fermentation Process
Other articles include:

Role of Digital Microfluidics in Enabling Access to Laboratory Automation and Making Biology Programmable

Xcellerate Investigator Portal: A New Web-Based Tool for Online Delivery of Central Laboratory Data, Reports and Communications to Clinical Sites

Centrifugal Generation of Droplet-Based 3D Cell Cultures

U.S. adults increasingly experienced symptoms associated with acute stress and depression as COVID-19 cases and deaths skyrocketed between mid-March and mid-April 2020, according to a study of more than 6,500 people from three large, nationally representative cohorts. These symptoms were related to preexisting mental and physical health conditions, as well as secondary stressors such as job and wage loss. Acute stress and depressive symptoms were also related to greater COVID-19-related media consumption, a general increase in media consumption during the outbreak, and exposure to conflicting information in the media about the outbreak. E. Alison Holman and colleagues suggest these findings may be used to develop targeted public mental health interventions. While the scientific community has largely focused on understanding and treating COVID-19, little research has investigated the accompanying mental health crisis. Prior studies that examined the pandemic's mental health implications have relied on non-representative samples from opt-in online panels that may not accurately reflect the nation as a whole. Between March 18, 2020 and April 18, 2020, Holman et al. assessed acute stress; symptoms of depression; and direct, community, and media-based exposures to COVID-19 in three nationally representative cohorts (a total of more than 6,500 people) in staggered 10-day periods. Holman et al. found that while personal exposure to COVID-19, such as testing positive for the virus or coping with a close friend or family member's diagnosis, was associated with heightened anxiety and depression symptoms, community-level exposure was not. This suggests U.S. adults are more concerned with contracting the virus than dealing with pandemic-induced daily life disruptions.

HOUSTON - (Sept. 18, 2020) - Points matter when designing nanoparticles that drive important chemical reactions using the power of light.

Researchers at Rice University's Laboratory for Nanophotonics (LANP) have long known that a nanoparticle's shape affects how it interacts with light, and their latest study shows how shape affects a particle's ability to use light to catalyze important chemical reactions.

In a comparative study, LANP graduate students Lin Yuan and Minhan Lou and their colleagues studied aluminum nanoparticles with identical optical properties but different shapes. The most rounded had 14 sides and 24 blunt points. Another was cube-shaped, with six sides and eight 90-degree corners. The third, which the team dubbed "octopod," also had six sides, but each of its eight corners ended in a pointed tip.

All three varieties have the ability to capture energy from light and release it periodically in the form of super-energetic hot electrons that can speed up catalytic reactions. Yuan, a chemist in the research group of LANP director Naomi Halas, conducted experiments to see how well each of the particles performed as photocatalysts for hydrogen dissociation reaction. The tests showed octopods had a 10 times higher reaction rate than the 14-sided nanocrystals and five times higher than the nanocubes. Octopods also had a lower apparent activation energy, about 45% lower than nanocubes and 49% lower than nanocrystals.

"The experiments demonstrated that sharper corners increased efficiencies," said Yuan, co-lead author of the study, which is published in the American Chemical Society journal ACS Nano. "For the octopods, the angle of the corners is about 60 degrees, compared to 90 degrees for the cubes and more rounded points on the nanocrystals. So the smaller the angle, the greater the increase in reaction efficiencies. But how small the angle can be is limited by chemical synthesis. These are single crystals that prefer certain structures. You cannot make infinitely more sharpness."

Lou, a physicist and study co-lead author in the research group of LANP's Peter Nordlander, verified the results of the catalytic experiments by developing a theoretical model of the hot electron energy transfer process between the light-activated aluminum nanoparticles and hydrogen molecules.

"We input the wavelength of light and particle shape," Lou said. "Using these two aspects, we can accurately predict which shape will produce the best catalyst."

The research builds on LANP's efforts to develop methods of chemically synthesizing aluminum nanoparticles of varying shapes and sizes.

The work is part of an ongoing green chemistry effort by LANP to develop commercially viable light-activated nanocatalysts that can insert energy into chemical reactions with surgical precision. LANP has previously demonstrated catalysts for ethylene and syngas production, the splitting of ammonia to produce hydrogen fuel and for breaking apart "forever chemicals."

"This study shows that photocatalyst shape is another design element engineers can use to create photocatalysts with the higher reaction rates and lower activation barriers," said Halas, Rice's Stanley C. Moore Professor of Electrical and Computer Engineering, director of Rice's Smalley-Curl Institute and a professor of chemistry, bioengineering, physics and astronomy, and materials science and nanoengineering.

In the past decade, researchers have engineered an array of new tools that control the balance of genetic inheritance. Based on CRISPR technology, such gene drives are poised to move from the laboratory into the wild where they are being engineered to suppress devastating diseases such as mosquito-borne malaria, dengue, Zika, chikungunya, yellow fever and West Nile. Gene drives carry the power to immunize mosquitoes against malarial parasites, or act as genetic insecticides that reduce mosquito populations.

Although the newest gene drives have been proven to spread efficiently as designed in laboratory settings, concerns have been raised regarding the safety of releasing such systems into wild populations. Questions have emerged about the predictability and controllability of gene drives and whether, once let loose, they can be recalled in the field if they spread beyond their intended application region.

Now, scientists at the University of California San Diego and their colleagues have developed two new active genetic systems that address such risks by halting or eliminating gene drives in the wild. On Sept.18, 2020 in the journal Molecular Cell, research led by Xiang-Ru Xu, Emily Bulger and Valentino Gantz in the Division of Biological Sciences offers two new solutions based on elements developed in the common fruit fly.

"One way to mitigate the perceived risks of gene drives is to develop approaches to halt their spread or to delete them if necessary," said Distinguished Professor Ethan Bier, the paper's senior author and science director for the Tata Institute for Genetics and Society. "There's been a lot of concern that there are so many unknowns associated with gene drives. Now we have saturated the possibilities, both at the genetic and molecular levels, and developed mitigating elements."

The first neutralizing system, called e-CHACR (erasing Constructs Hitchhiking on the Autocatalytic Chain Reaction) is designed to halt the spread of a gene drive by "shooting it with its own gun." e-CHACRs use the CRISPR enzyme Cas9 carried on a gene drive to copy itself, while simultaneously mutating and inactivating the Cas9 gene. Xu says an e-CHACR can be placed anywhere in the genome.

"Without a source of Cas9, it is inherited like any other normal gene," said Xu. "However, once an e-CHACR confronts a gene drive, it inactivates the gene drive in its tracks and continues to spread across several generations 'chasing down' the drive element until its function is lost from the population."

The second neutralizing system, called ERACR (Element Reversing the Autocatalytic Chain Reaction), is designed to eliminate the gene drive altogether. ERACRs are designed to be inserted at the site of the gene drive, where they use the Cas9 from the gene drive to attack either side of the Cas9, cutting it out. Once the gene drive is deleted, the ERACR copies itself and replaces the gene-drive.

"If the ERACR is also given an edge by carrying a functional copy of a gene that is disrupted by the gene drive, then it races across the finish line, completely eliminating the gene drive with unflinching resolve," said Bier.

The researchers rigorously tested and analyzed e-CHACRs and ERACRs, as well as the resulting DNA sequences, in meticulous detail at the molecular level. Bier estimates that the research team, which includes mathematical modelers from UC Berkeley, spent an estimated combined 15 years of effort to comprehensively develop and analyze the new systems. Still, he cautions there are unforeseen scenarios that could emerge, and the neutralizing systems should not be used with a false sense of security for field-implemented gene drives.

"Such braking elements should just be developed and kept in reserve in case they are needed since it is not known whether some of the rare exceptional interactions between these elements and the gene drives they are designed to corral might have unintended activities," he said.

According to Bulger, gene drives have enormous potential to alleviate suffering, but responsibly deploying them depends on having control mechanisms in place should unforeseen consequences arise. ERACRs and eCHACRs offer ways to stop the gene drive from spreading and, in the case of the ERACR, can potentially revert an engineered DNA sequence to a state much closer to the naturally-occurring sequence.

"Because ERACRs and e-CHACRs do not possess their own source of Cas9, they will only spread as far as the gene drive itself and will not edit the wild type population," said Bulger. "These technologies are not perfect, but we now have a much more comprehensive understanding of why and how unintended outcomes influence their function and we believe they have the potential to be powerful gene drive control mechanisms should the need arise."

Allowing yourself a few minutes of downtime significantly boosts mental and physical relaxation. Research by psychologists at the University of Konstanz observed higher levels of psychological and physiological relaxation in people after only ten minutes of receiving a massage. Even ten minutes of simple rest increased relaxation, albeit to a lesser degree than massage. The findings, reported on 8 September 2020 in the journal Scientific Reports, provide the first indication that short-term treatments can robustly reduce stress on a psychological and physiological level by boosting the body's principal engine for relaxation - the parasympathetic nervous system (PNS).

Stress is known to have negative consequences for health and disease. However, our bodies have an inbuilt regenerative system, the PNS, to ward off stress during times of threat. Launching a relaxation response is thus key to protecting our health and restoring balance in our body. Massage has been used to improve relaxation, yet no systematic approach exists to robustly confirm its effect on the PNS and whether or not this could be used as rehabilitation for patients suffering from stress-related disease.

Boosting the body's engine for relaxation

This study indicates that massage is an easy-to-apply intervention that can boost the body's principal engine for relaxation - the PNS - and also lead to a reduction in perceived mental stress. The discovery that massage is effective on the level of both psychology and physiology via the PNS will pave the way for future studies on understanding the role of relaxation on stress.

"To get a better handle on the negative effects of stress, we need to understand its opposite - relaxation," says Jens Pruessner, head of the Neuropsychology lab and Professor at the Cluster of Excellence "Centre for the Advanced Study of Collective Behaviour" at the University of Konstanz. "Relaxation therapies show great promise as a holistic way to treat stress, but more systematic scientific appraisal of these methods is needed."

Standardised testing approach

Researchers from the Department of Psychology in Konstanz developed a standardised approach for testing if tactile stimulation could improve mental and physical relaxation. They applied two different ten-minute massages on human subjects in the laboratory to test: A head-and-neck massage was designed to actively stimulate the PNS by applying moderate pressure on the vagal nerve, which is the largest nerve running to the PNS. Then a neck-and-shoulder massage with soft stroking movements was designed to examine whether just touch can also be relaxing. Finally, a control group of participants sitting quietly at a table was tested for the effect of rest without tactile stimulation. Physiological relaxation was gauged by monitoring the heart rate of participants and measuring heart rate variability (HRV), which indicates how flexibly the PNS can respond to changes in the environment. The higher the HRV, the more relaxed is the body. Psychological relaxation was gauged by asking participants to describe how relaxed or stressed they feel.

Ten minutes of resting or receiving either massage resulted in psychological and physiological reduction in stress. All participants reported that they felt more relaxed, and less stressed, compared with before the treatments. Further, all participants showed significant increases in heart rate variability, which demonstrates that the PNS was activated and the body physiologically relaxed just by resting alone. The physiological effect was more pronounced when participants received a massage. It was, however, not important whether the massage was soft or moderate - tactile contact in general seemed to improve the relaxation of the body.

Small moments with big impact

"We are very encouraged by the findings that short periods of dis-engagement are enough to relax not just the mind but also the body," says Maria Meier, a doctoral student in the lab of Neuropsychology and first author on the study. "You don't need a professional treatment in order to relax. Having somebody gently stroke your shoulders, or even just resting your head on the table for ten minutes, is an effective way to boost your body's physiological engine of relaxation."

By developing a standardised method for robustly testing and validating relaxation therapies, the study allows further experiments to test the effects of additional relaxation interventions that could be used in prevention or rehabilitation programmes for people suffering from stress-related diseases such as depression.

"Massage, being such a commonly used relaxation therapy, was our first study," says Meier. "Our next step is to test if other short interventions, like breathing exercises and meditation, show similar psychological and physiological relaxation results."

To capture panoramic views in a single shot, photographers typically use fisheye lenses -- ultra-wide-angle lenses made from multiple pieces of curved glass, which distort incoming light to produce wide, bubble-like images. Their spherical, multipiece design makes fisheye lenses inherently bulky and often costly to produce.

Now engineers at MIT and the University of Massachusetts at Lowell have designed a wide-angle lens that is completely flat. It is the first flat fisheye lens to produce crisp, 180-degree panoramic images. The design is a type of "metalens," a wafer-thin material patterned with microscopic features that work together to manipulate light in a specific way.

In this case, the new fisheye lens consists of a single flat, millimeter-thin piece of glass covered on one side with tiny structures that precisely scatter incoming light to produce panoramic images, just as a conventional curved, multielement fisheye lens assembly would. The lens works in the infrared part of the spectrum, but the researchers say it could be modified to capture images using visible light as well.

The new design could potentially be adapted for a range of applications, with thin, ultra-wide-angle lenses built directly into smartphones and laptops, rather than physically attached as bulky add-ons. The low-profile lenses might also be integrated into medical imaging devices such as endoscopes, as well as in virtual reality glasses, wearable electronics, and other computer vision devices.

"This design comes as somewhat of a surprise, because some have thought it would be impossible to make a metalens with an ultra-wide-field view," says Juejun Hu, associate professor in MIT's Department of Materials Science and Engineering. "The fact that this can actually realize fisheye images is completely outside expectation.

This isn't just light-bending -- it's mind-bending."

Hu and his colleagues have published their results in the journal Nano Letters. Hu's MIT coauthors are Mikhail Shalaginov, Fan Yang, Peter Su, Dominika Lyzwa, Anuradha Agarwal, and Tian Gu, along with Sensong An and Hualiang Zhang of UMass Lowell.

Design on the back side

Metalenses, while still largely at an experimental stage, have the potential to significantly reshape the field of optics. Previously, scientists have designed metalenses that produce high-resolution and relatively wide-angle images of up to 60 degrees. To expand the field of view further would traditionally require additional optical components to correct for aberrations, or blurriness -- a workaround that would add bulk to a metalens design.

Hu and his colleagues instead came up with a simple design that does not require additional components and keeps a minimum element count. Their new metalens is a single transparent piece made from calcium fluoride with a thin film of lead telluride deposited on one side. The team then used lithographic techniques to carve a pattern of optical structures into the film.

Each structure, or "meta-atom," as the team refers to them, is shaped into one of several nanoscale geometries, such as a rectangular or a bone-shaped configuration, that refracts light in a specific way. For instance, light may take longer to scatter, or propagate off one shape versus another -- a phenomenon known as phase delay.

In conventional fisheye lenses, the curvature of the glass naturally creates a distribution of phase delays that ultimately produces a panoramic image. The team determined the corresponding pattern of meta-atoms and carved this pattern into the back side of the flat glass.

'We've designed the back side structures in such a way that each part can produce a perfect focus," Hu says.

On the front side, the team placed an optical aperture, or opening for light.

"When light comes in through this aperture, it will refract at the first surface of the glass, and then will get angularly dispersed," Shalaginov explains. "The light will then hit different parts of the backside, from different and yet continuous angles. As long as you design the back side properly, you can be sure to achieve high-quality imaging across the entire panoramic view."

Across the panorama

In one demonstration, the new lens is tuned to operate in the mid-infrared region of the spectrum. The team used the imaging setup equipped with the metalens to snap pictures of a striped target. They then compared the quality of pictures taken at various angles across the scene, and found the new lens produced images of the stripes that were crisp and clear, even at the edges of the camera's view, spanning nearly 180 degrees.

"It shows we can achieve perfect imaging performance across almost the whole 180-degree view, using our methods," Gu says.

In another study, the team designed the metalens to operate at a near-infrared wavelength using amorphous silicon nanoposts as the meta-atoms. They plugged the metalens into a simulation used to test imaging instruments. Next, they fed the simulation a scene of Paris, composed of black and white images stitched together to make a panoramic view. They then ran the simulation to see what kind of image the new lens would produce.

"The key question was, does the lens cover the entire field of view? And we see that it captures everything across the panorama," Gu says. "You can see buildings and people, and the resolution is very good, regardless of whether you're looking at the center or the edges."

The team says the new lens can be adapted to other wavelengths of light. To make a similar flat fisheye lens for visible light, for instance, Hu says the optical features may have to be made smaller than they are now, to better refract that particular range of wavelengths. The lens material would also have to change. But the general architecture that the team has designed would remain the same.

The researchers are exploring applications for their new lens, not just as compact fisheye cameras, but also as panoramic projectors, as well as depth sensors built directly into smartphones, laptops, and wearable devices.

"Currently, all 3D sensors have a limited field of view, which is why when you put your face away from your smartphone, it won't recognize you," Gu says. "What we have here is a new 3D sensor that enables panoramic depth profiling, which could be useful for consumer electronic devices."

HSE University researchers have confirmed that the level of phonological processing skills in children can impact their ability to master reading. Complex phonological tests are best suited to detect phonological impairment. The study was published on September 6, 2020, in the Journal of Research in Reading.

Phonological processing is the ability to distinguish phonemes (minimal distinctive linguistic sounds), analyse sound sequences, and perform various operations with phonemes. These are the skills children master at an early age. Numerous international studies have proven that there is a correlation between phonological processing and reading abilities, and this is true not only for the English language. Meanwhile, the correlation between phonological skills and reading in Russian remains an under-researched area. In addition, it has remained elusive which phonological tests are the most predictive for people's reading skills.

To find this out, researchers from HSE University's Center for Language and Brain developed seven phonological tests of varying complexity. The complexity of a given test wasmeasured as the number of linguistic processes involved for an individual's successful performance on a particular task. In the simplest test, the participants answered whether the sound consequences they hear are different or the same, after listening to recording with, for example, the sound of 'bom/pom' or 'eva/eva'. This only requires decoding input sounds and minimum involvement of one's working memory. For the most complex tests, children were asked to count phonemes in a word pronounced by a speaker, or replace one of the sounds in a pseudoword. This task requires the ability to decode input sounds, recognize words (i.e., involve lexical access), and involve one's working memory, as well as perform sound analysis and other operations with phonemes.

The researchers invited 90 typically developing children aged seven to eleven from three schools in Moscow and Volgograd to participate in the experiment. All of them had confirmed normal hearing and vision, and had earlier successfully passed a screening for nonverbal intelligence. Each child took part in all seven phonological tests, followed by an assignment to evaluate their reading skills. For that, children had to read two short texts aloud, followed by questions on their contents. This allowed the researchers to assess children's reading fluency (i.e., the number of words read accurately in the first minute) and reading comprehension (i.e., the number of correct responses to the questions).

It was shown that the more errors the participants made as the complexity of the phonological tests increased, the fewer words they were able to read in a single minute. More complex phonological tests were better in predicting an individual's reading fluency, with less school students being able to pass them successfully. A specially developed statistical model demonstrated that the individual costs of adding one more linguistic process to a phonological test are significantly correlated with reading performance. Nevertheless, the question remains: how does reading comprehension correlate with phonological skills? This issue requires further investigation.

'Stand-alone tasks are insufficient, since children without any phonological deficit can also make singular errors. Simple phonological tests may be not discriminative enough, as they do not help to distinguish typically developing children from those disposed to reading disorders,' commented Svetlana Dorofeeva, one of the paper authors, who added: 'On the other hand, the completion of the whole set of seven tests for detecting phonological deficits can help to determine the extent of a certain problem, and choose the most effective assignments to develop phonological skills in a specific child.'

The results of this study can help improve the methods for diagnosing and dealing with reading problems, such as dyslexia. The researchers' conclusions confirm that in order to manage the phonological deficit, which may lead to reading disorders, it makes sense to use complex phonological tests.

Greenwood, SC (September 17, 2020) - Greenwood Genetic Center (GGC) researchers, in collaboration with scientists from Belgium, Spain, and Italy, have confirmed that variants in LMNB1 cause syndromic microcephaly with variable short stature, intellectual disability, and other neurological symptoms. The findings are reported in the October issue of the American Journal of Human Genetics.

The paper describes seven patients from five families with novel de novo variants in LMNB1, all with pronounced primary microcephaly as the core feature. Variants were identified through whole exome sequencing.

Functional analysis of each of the gene variants and resultant lamin B1 protein showed that these variants act in a dominant fashion to disrupt nuclear envelope integrity which in turn causes the nucleus to become misshapen.

"We used a HeLa cell system to analyze the three missense mutations in this gene and demonstrated impaired function of the nuclear lamina," said Tonya Moss, GGC research technologist and co-lead author along with Francesca Cristofoli, PhD, of University Hospitals Leuven in Belgium. "Two other variants displayed misshapen nuclei and a decrease in nuclear localization of the lamin B1 protein, and another showed an increased frequency of condensed nuclei."

Duplications in LMNB1 are a known cause of autosomal dominant adult-onset leukodystrophy, but this paper is the first to show that variants in this gene can cause congenital abnormalities through nuclear envelope disruption.

"Because this gene product has multiple domains, it is likely that different variants in LMNB1 will work by different mechanisms, necessitating a case-by-case analysis of pathogenicity, which is important for future treatment studies as well as reproductive planning for families," said Richard Steet, PhD, co-corresponding author and Director of Research at the JC Self Research Institute at GGC. "These findings add LMNB1 to the growing list of genes implicated in severe autosomal dominant microcephaly and broadens the phenotypic spectrum of the laminopathies."

High-speed cameras can take pictures in quick succession. This makes them useful for visualizing ultrafast dynamic phenomena, such as femtosecond laser ablation for precise machining and manufacturing processes, fast ignition for nuclear fusion energy systems, shock-wave interactions in living cells, and certain chemical reactions.

Among the various parameters in photography, the sequential imaging of microscopic ultrafast dynamic processes requires high frame rates and high spatial and temporal resolutions. In current imaging systems, these characteristics are in a tradeoff with one another.

However, scientists at Shenzhen University, China, have recently developed an all-optical ultrafast imaging system with high spatial and temporal resolutions, as well as a high frame rate. Because the method is all-optical, it's free from the bottlenecks that arise from scanning with mechanical and electronic components.

Their design focuses on non-collinear optical parametric amplifiers (OPAs). An OPA is a crystal that, when simultaneously irradiated with a desired signal light beam and a higher-frequency pump light beam, amplifies the signal beam and produces another light beam known as an idler. Because the crystal used in this study is non-collinear, the idler is fired in a different direction from that of the signal beam. But how is such a device useful in a high-speed imaging system?

The answer lies in cascading OPAs. The information of the target, contained in the signal beam, is mapped onto the idler beam by the OPA while the pump beam is active. Because the idler moves in a different direction, it can be captured using a conventional charge-coupled device (CCD) camera "set to the side" while the signal beam moves toward the next stage in the OPA cascade.

Just like how water would descend in a waterfall, the signal beam reaches the subsequent OPA, and the pump beam generated from the same laser source activates it; except now, a delay line makes the pump beam arrive later, causing the CCD camera next to the OPA in the second stage to take a picture later. Through a cascade of four OPAs with four associated CCD cameras and four different delay lines for the pump laser, the scientists created a system that can take four pictures in extremely quick succession.

The speed of capturing consecutive pictures is limited by how small the difference between two laser delay lines can be. In this regard, this system achieved an effective frame rate of 15 trillion frames per second - a record shutter speed for high-spatial-resolution cameras. Conversely, the temporal resolution depends on the duration of the laser pulses triggering the OPAs and generating the idler signals. In this case, the pulse width was 50 fs (fifty millionths of a nanosecond). Coupled with the incredibly fast frame rate, this method is able to observe ultrafast physical phenomena, such as an air plasma grating and a rotating optical field spinning at 10 trillion radians per second.

According to Anatoly Zayats, Co-Editor-in-Chief of Advanced Photonics, "The team at Shenzhen University has demonstrated ultrafast photographic imaging with the record fastest shutter speed. This research opens up new opportunities for studies of ultrafast processes in various fields."

This imaging method has scope for improvement but could easily become a new microscopy technique. Future research will unlock the potential of this approach to give us a clearer picture of ultrafast transient phenomena.

About a year ago, a conversation during a faculty meeting piqued Marcus Crede's interest. A senior faculty member in Iowa State University's Department of Psychology said that he believed frequent quizzes help students better grasp classroom material. Crede, an associate professor of psychology, was skeptical that something as simple as a quiz could positively impact students' academic performance. He decided to dig deeper and conduct a meta-analytic study of existing research to see if there was any merit to the claim. What he discovered truly surprised him.

"I have a long history of trying to understand the variables that contribute to learning and performance in the classroom," Crede said. "For me, this study is part of a larger effort to understand what works and what doesn't work. It turned out to be a much more interesting paper than I thought it was going to be. I was surprised."

The study

Crede teamed up with psychology graduate student Lukas Sotola, who took the lead on much of the research. They analyzed data from previously published studies that examined 52 classes with almost 8,000 students, primarily college-level courses, to determine if frequent quizzes improved the students' academic performance. Laboratory settings were excluded from the study because Crede and Sotola wanted to observe whether similar studies from labs would apply to general classrooms. They defined quizzes as low-stakes assessments of learned material that occurred at least once a week.

Crede emphasizes that this study did not involve true experiments, where some students were randomly assigned quiz conditions and others were not.

"As soon as we don't have random assignments, we can't be 100% certain that the difference is really do to the quizzes. It could be something else."

Nevertheless, the results suggest there may be a strong link between frequent quizzing and student success.

The study's results are detailed in the paper, "Regarding Class Quizzes: A Meta-analytic Synthesis of Studies on the Relationship Between Frequent Low-stakes Testing and Class Performance," published last month in the journal Educational Psychology Review.

A few surprises

Crede and Sotola discovered that when students are quizzed over class material at least once a week, they tend to perform better on midterm and final exams compared to students who did not take quizzes. They also found that students who took frequent quizzes were less likely to fail the class, especially if they were struggling with the course content.

"I was surprised the effect of quizzes was relatively strong," Crede said. "I was skeptical. I didn't think this would have much of an effect. The other surprising thing was how much quizzes helped reduce failure rates in classes. The odds of passing a class went through the roof where instructors used this."

Even if quizzes only modestly impact students' ability to pass a class, Sotola said this tool should be part of an instructor's teaching curriculum.

"A modest effect can have a large impact over the course of many years," Sotola said. "If quizzes improve performance and lead to even a slightly lower percentage of students failing their classes, then that will presumably have positive effects on graduation and drop-out rates down the road, which will save students and institutions time and money."

Crede noted that students who struggle the most in a class seem to benefit the greatest from frequent quizzes. This is a profound finding, he said, especially since implementing short quizzes into course curriculum is a relatively simple task.

"In many universities, including Iowa State, there's often concern about drop-out rates and failure rates, and so the fact that we can apparently do so much with so little effort is really encouraging for us," Crede said.

In addition to quiz frequency, another factor that seemed to positively impact students' performance was immediate feedback from instructors. Also, Crede and Sotola said quizzes that required students to answer with written responses proved more beneficial to their understanding of class material compared to multiple-choice questions, though their pool of data for this particular aspect of the study was small.

"You have to be cautious about the amount of data we have, but multiple-choice questions seem to be a little less effective than what we call a constructive-response question, when you actually have to come up with the answer yourself," Crede said. "It's about recognizing the right answer and actually remembering what the right answer is."

Crede acknowledges that asking teachers to grade written quizzes daily or weekly may discourage some from implementing them in their classes. Instead, he recommends instructors utilize online quizzes that can be automatically graded by a course management system, such as Canvas.

Crede and Sotola said some quiz attributes proved insignificant in their study, including whether the tests were pop quizzes versus planned, or if they were online or on paper. No matter how they are delivered, Crede and Sotola agree that their study shows frequent quizzes with immediate instructor feedback help students, especially those who are having difficulties, succeed in the classroom.

"The impact on struggling students was really remarkable," Crede said. "Again, we only have data on about 1,000 students, but it's really quite dramatic. If it's even remotely in that neighborhood, this is something we should all be doing."

Fruit flies have the uncanny ability to wake up from a months-long hibernation right when their food of choice—say, the fruit from apple or Hawthorn trees—is at its peak. They’re active for a couple of weeks, eating and mating, before going dormant for the rest of the year. How this synchronization and remarkable timing happens has long been a mystery. In a world where global climate change is shifting the growing seasons, somehow the fruit flies keep up.

In a new study, scientists have found many genes responsible for setting the flies’ internal alarm clock and found that an imperceptibly slow development during dormancy is key to their rapid genetic adaption.

The study is published in the journal PNAS.

Internal Seasonal Timers

Like bears or ground squirrels, fruit flies time their slumber to coincide with seasonal food availability. They even evolve quickly enough to, say, shorten their dormancy to exploit longer growing seasons. Though some species rely on the predictable shortening and lengthening of days to cue their hibernation (called photoperiodism), others appear to have an internal mechanism.

“In addition to the 24-hour circadian clock that we all have, many fruit flies have an internal seasonal timer,” says study co-author Gregory Ragland, PhD, assistant professor of integrative biology at University of Colorado Denver. “They pop up, exploit their host, and disappear for nine or 10 months. There’s a useful marriage between what we know about the ecology and genetics of this process, which is why we approached this as a collaborative effort.”

Unlike photoperiodism, much of this particular type of dormancy, or diapause, remains unknown. To investigate, a team of researchers led by Edwina Dowle, PhD, and Ragland at CU Denver, and Tom Powell, PhD, and Daniel Hahn, PhD, at University of Florida, joined forces with Jeff Feder, PhD, from University of Notre Dame and Stewart Berlocher, PhD, from University of Illinois at Urbana–Champaign.

Tracking the Rate of Development

The group explored the hypothesis that differences in the rate of development during diapause drive the differences in the timing of seasonal activity. To test it, they collected two populations of the Rhagoletis pomonella flies that have one generation per year and overwinter as diapausing pupae. One population eats hawthorn berries, which are native to North America, while the other evolved the ability to eat apples introduced by colonists in North America about 400 years ago.

“Though it’s actually a fly larva, this is the proverbial ‘worm’ in the apple that has evolved into a major crop pest by adjusting its timing to coincide with the early fruiting time of apple,” says Ragland.

The researchers monitored the apple and haw flies in a lab, simulating overwintering for designated time intervals. During each interval, they tested the flies’ transcriptome, the bundle of RNA transcripts that determines traits. Sampling from the fly brains, researchers can compare snapshots of the RNA composition to measure developmental differences in the nervous system over long time periods.

“Watching their morphology over time, they appear to be in suspended animation” says Ragland. “But the brain transcriptome revealed subtle, yet steady developmental changes that accumulated over six months, eventually completing the process that cued them to pop out of dormancy.”

Polygenic Traits Key to a Speedy Evolution

This provides a possible mechanism that flies use to set their seasonal timer. The process also appears to be key for the rapid evolution of seasonality—apple flies have a slightly faster rate of development during dormancy, causing them to emerge earlier in the year.

By comparing genetic variants differing in the two fly populations, researchers found that polygenic traits led to the quickness of adaptation; many genes, each with very small effects, worked together to determine the rate of development. The research illustrates that crop pests and insect disease vectors with similar biology may rapidly respond to changing climates by a similar genetic mechanism.

Understanding the mechanics of diapause could also have a big impact on biomedical research, which depends on massive genetic stocks of the Drosophila fly curated in labs all over the world.

“People are interested in how to best preserve these flies because we can’t cryogenically preserve them yet,” says Ragland. “But if we could modify these lines to go into diapause, it would be a huge breathrough.”

Journal

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2002357117

An Australian collaboration has reviewed the fundamental theories underpinning the quantum anomalous Hall effect (QAHE).

QAHE is one of the most fascinating and important recent discoveries in condensed-matter physics.

It is key to the function of emerging 'quantum' materials, which offer potential for ultra-low energy electronics.

QAHE causes the flow of zero-resistance electrical current along the edges of a material.

QAHE IN TOPOLOGICAL MATERIALS: KEY TO LOW-ENERGY ELECTRONICS

Topological insulators, recognised by the Nobel Prize in Physics in 2016, are based on a quantum effect known as the quantum anomalous Hall effect (QAHE).

"Topological insulators conduct electricity only along their edges, where one-way 'edge paths' conducts electrons without the scattering that causes dissipation and heat in conventional materials," explains lead author Muhammad Nadeem.

QAHE was first proposed by 2016 Nobel-recipient Prof Duncan Haldane (Manchester) in the 1980s, but it subsequently proved challenging to realize QAHE in real materials. Magnetic-doped topological insulators and spin-gapless semiconductors are the two best candidates for QAHE.

It's an area of great interest for technologists," explains Xiaolin Wang. "They are interested in using this significant reduction in resistance to significantly reduce the power consumption in electronic devices."

"We hope this study will shed light on the fundamental theoretical perspectives of quantum anomalous Hall materials," says co-author Prof Michael Fuhrer (Monash University), who is Director of FLEET.

THE STUDY

The collaborative, theoretical study concentrates on these two mechanisms:

large spin-orbit coupling (interaction between electrons' movement and their spin)

strong intrinsic magnetization (ferromagnetism)

A new study by researchers at the University of Illinois Chicago and the University of Pittsburgh suggests that a significant proportion of older patients receiving opioids at dental visits also use psychotropic medications -- a potentially harmful combination. Their findings are published in the journal Pharmacotherapy.

Rates of polypharmacy, or taking multiple medications, are high among older adults who are more likely to be managing more than one health issue at any given time. Psychotropic medications that act on the central nervous system, such as antianxiety or antidepressant medications, are especially dangerous if taken with opioids because they can interact with each other and have negative effects.

"Some of the most concerning negative outcomes of these combinations include overdosing on opioids or falling, which can necessitate a visit to the hospital, which in itself carries greater risk for older adults," said Gregory Calip, associate professor of pharmacy systems, outcomes and policy at the UIC College of Pharmacy and corresponding author on the paper.

The researchers looked at medical, dental and pharmacy claims data from 40,800 older adult dental patients who visited a dentist between 2011 and 2015 and were prescribed opioids. The data was from the IBM Watson MarketScan databases.

The average age of the patients included in the study was 69 years old and 45% were female. Of these patients, 10% were taking medications that are associated with increased risks for harm with opioid prescriptions.

There were a total of 947 hospitalizations or emergency room visits among these patients.

The researchers found that among patients prescribed opioids by their dentist, 1 in 10 were already taking a prescription medication that should not be prescribed with opioids.

They also found that patients inappropriately prescribed an opioid medication combination by their dentist were 23% more likely to be hospitalized or visit an emergency department in the 30 days after the dental visit where they were prescribed an opioid, compared with dental patients who were not prescribed an opioid medication.

"Dentists are among the top prescribers of opioids," said Katie Suda, professor of medicine at the University of Pittsburgh School of Medicine and principal investigator of the study. "It seems that the increased messaging regarding limiting opioid prescriptions has been aimed primarily at medical physicians and not tailored to other specialist providers, including dentists. This can have dire consequences. As we saw in our study, opioid interactions with other medications was likely responsible for the significant rise in emergency room visits and hospitalizations."

"Although the percentage of opioids prescribed by dentists has decreased in the last 20 years, dentists must continue interprofessional collaboration with primary care physicians, pharmacists, and other health care providers to address devastating and preventable drug interactions affecting vulnerable patients who look to them for safe and compassionate care," said Dr. Susan Rowan, executive associate dean and associate dean for clinical affairs at the UIC College of Dentistry.