Culture

Genetics of the tree of life

image: The African baobab tree has 168 chromosomes in total. USDA researchers used fluorescent probes to see the genetic components of individual chromosomes within the cells.

Image: 
Islam-Faradi, Sakhanokho & Nelson

The African baobab tree (Adansonia digitata) is called the tree of life. Baobab trees can live for more than a thousand years and provide food, livestock fodder, medicinal compounds, and raw materials. Baobab trees are incredibly significant. However, there are growing conservation concerns and until now, a lack of genetic information.

The African baobab tree has 168 chromosomes - critical knowledge for further genetic studies, conservation, and improvement for agricultural purposes. The findings were published in the journal Scientific Reports. Previous studies estimated that the tree has between 96 and 166 chromosomes.

"We were able to unequivocally count the chromosomes," says Nurul Faridi, a USDA Forest Service research geneticist who co-led the study with Hamidou Sakhanokho, a USDA Agricultural Research Service research geneticist.

The researchers used fluorescent probes to see the genetic components of individual chromosomes within the cells - which glow like jewels.

The analysis also revealed that the tree has a massive nucleolus organizer region (NOR). Relative to the main chromosome body, this region appears larger than that of any other plant species. During certain stages of the cell cycle, nucleoli form at the NORs. The nucleoli are essential for ribosome assembly and protein synthesis in eukaryotes and are an important feature that differentiates eukaryotes from prokaryotes.

"These genetic findings are foundational and will make genetic conservation of the African baobab tree more efficient and effective," says Dana Nelson, a coauthor and project leader of the Southern Research Station's genetic unit. "This research is also a precursor for tree breeding programs seeking to improve baobab for silvicultural applications."

Credit: 
USDA Forest Service ‑ Southern Research Station

Mouse-adapted SARS-CoV-2 model provides new tool for COVID-19 discoveries

CHAPEL HILL, N.C. - A new COVID-19 mouse model developed at the University of North Carolina at Chapel Hill captures many of the features of human disease and has helped advance a COVID-19 vaccine candidate to clinical trial.

Researchers, among them virologists and microbiologists at UNC-Chapel Hill's Gillings School of Global Public Health, describe the mouse-adapted SARS-CoV-2 model in a paper fast-tracked and published Aug. 27 in Nature.

Small animal models that replicate SARS-CoV-2 are desperately needed to rapidly evaluate medical countermeasures. The mouse model developed in the laboratory of virologist Ralph Baric has already been used to accelerate the development of Operation Warp Speed vaccines such as those by Moderna.

The model is expected to have a positive impact on the development of antivirals, vaccines and antibodies for the fight against COVID-19, which has risen to 5.7 million cases in the U.S. and continues to be widespread in some communities.

In January, as scientists began gearing up to research the dangerous new illness, all eyes were on ACE2, a protein that sits on the surface of many types of cells in the human body including the heart, gut, lungs and inside the nose. SARS-CoV-2, the coronavirus that causes COVID-19, latches on to ACE2 receptor and uses it to enter cells and begin growing, leading to infection.

But it was discovered that SARS-CoV-2 cannot use the mouse version of the viral receptor ACE2. The Baric laboratory has a history of generating mouse models of other coronaviruses, such as SARS-CoV and MERS-CoV, so the team used their expertise to adapt SARS-CoV2 to use the mouse receptor.

They changed two amino acid positions in the viral genome to generate a mouse-adapted virus capable of infecting standard laboratory mice.

It worked, said study co-author Sarah R. Leist, a research associate at UNC-Chapel Hill, "generating mild symptoms in young mice and in old mice, we saw more severe disease in line with what has been reported in the human population."

By spring the laboratory was able to begin many studies involving mice.

"We have used our SARS-CoV-2 mouse adapted model to test a few medical countermeasures already," said lead study author Kenneth H. Dinnon III, a graduate research assistant in the Gillings School of Global Public Health. "We have collaborated with the National Institutes of Health Vaccine Research Center and Moderna to test their mRNA-1273 human vaccine candidate and shown that the therapy effectively protected mice from infection. We have also worked with several academic groups to test other vaccines platforms, including alphavirus replicon platforms developed in our own laboratory."

The model is helping to make inroads in another therapeutic avenue: antibodies which are designed to harness the body's ability to target and fight threats.

The team has worked with other labs to identify and test the best human monoclonal antibodies capable of binding and neutralizing SARS-CoV-2 in mice.

Experiments described in the Nature study found mice given single injections of interferon lambda-1a either before or after infection with SARS-CoV-2 protected mice from virus replication and loss of lung function.

The mouse model is the first to show that this kind of treatment works against SARS-CoV-2 in a living organism. The finding supports clinical trials ongoing at Stanford University.

Such milestones are part of the track record of researchers in the Baric lab at UNC-Chapel Hill's Gillings School of Global Public Health. Lab work at Gillings accelerated the antiviral remdesivir to clinical trial. Today, remdesivir is in demand worldwide for its ability to speed recovery among hospitalized COVID-19 patients.

"This new mouse model will be available to other researchers and will allow the greater research community a system to understand how the virus causes diseases and to test various therapies and vaccines under development around the country and world," said Baric, a professor of epidemiology and microbiology and immunology at UNC-Chapel Hill.

Credit: 
University of North Carolina at Chapel Hill

Estrogen may lessen severity of COVID-19 symptoms in women, study says

WINSTON-SALEM, N.C. - Aug. 27, 2020 - Why are men at greater risk than women for more severe symptoms and worse outcomes from COVID-19 regardless of age?

In an effort to understand why this occurs, scientists at Wake Forest School of Medicine conducted a review of published preclinical data on sex-specific hormone activity, especially estrogen. The review is published in the September online issue of the journal Current Hypertension Reports.

"We know that coronavirus affects the heart and we know that estrogen is protective against cardiovascular disease in women, so the most likely explanation seemed to be hormonal differences between the sexes," said the lead author of the review, Leanne Groban, M.D., professor of anesthesiology at Wake Forest School of Medicine, part of Wake Forest Baptist Health.

Groban's researchers said the published literature indicated that the angiotensin-converting enzyme2 (ACE2), which is attached to cell membranes in the heart, arteries, kidneys and intestines, is the cellular receptor of the coronavirus responsible for COVID-19 infections, and helps bring the virus into the cells of those organ systems.

The review, they said, also pointed to estrogen's lowering the level of ACE2 in the heart, which may modulate the severity of COVID-19 in women. Conversely, higher levels of ACE2 in tissues could account for why symptoms are worse in men than women, Groban said.

"We hope that our review regarding the role of estrogenic hormones in ACE2 expression and regulation may explain the gender differences in COVID-19 infection and outcomes, and serve as a guide for current treatment and the development of new therapies," Groban said.

Credit: 
Atrium Health Wake Forest Baptist

Songbirds reduce reproduction to help survive drought

image: An indigo flycatcher visits its nest in Malaysia.

Image: 
Photo by Thomas Martin

MISSOULA - With climate change heating the globe, drought more frequently impacts the reproduction and survival of many animal species.

New research from the University of Montana suggests tropical songbirds in both the Old and New Worlds reduce reproduction during severe droughts, and this - somewhat surprisingly - may actually increase their survival rates.

The work was published Aug. 24 in the journal Nature Climate Change by UM research scientist Thomas Martin and doctoral student James Mouton.

"We were extremely surprised to find that not only did reductions in breeding activity mitigate costs to survival, many long-lived species actually experienced higher survival rates during the drought year than during non-drought years," said Martin, assistant unit leader of UM's Montana Cooperative Wildlife Research Unit. "In contrast, shorter-lived species that kept breeding during droughts faced strong reductions in survival."

Martin has spent his career venturing into remote jungles and living there for months to study the lives of birds. For this work, he and Mouton studied 38 different bird species in Venezuela and Malaysia over multiple years. There was one drought year for each field site, and the authors modeled future population results for the birds using three different climate change scenarios.

They knew behavioral responses to drought might determine the relative impacts on survival and reproduction. At the jungle study sites, researchers located and monitored nests of all species over many years to examine reproductive activity prior to and during the droughts. They also banded birds with colored material and used intensive re-sighting of these birds to obtain rigorous estimates of survival.

The researchers found drought reduced reproduction an average of 36% in the 20 Malaysian species and 52% in the 18 Venezuelan species.

"The negative impacts of drought on survival are well documented," Martin said. "We therefore also expected the droughts to reduce survival, but thought that the reduced breeding activity might limit the decrease in survival."

He said they found the population impacts of droughts were largely nullified by the reproductive behavioral shifts in longer-lived species, but shorter-lived species saw less of a benefit.

"Overall, our results have several major implications," Martin said. "First, we show that understanding behavioral responses to drought are critical for predicting population responses. Behavioral responses to environmental conditions can help buffer the most sensitive vital rates for a given species and mitigate the overall effect on fitness.

"Second, our results provide unique support to the idea that reproduction can negatively affect survival," he said. "This idea of a 'cost of reproduction' is central to life history theory but only rarely documented in wild populations."

Finally, long-lived species are argued to be most sensitive to climate change, but the UM research suggests that many longer-lived species actually may be more resilient to drought impacts of climate change than previously expected.

"Ultimately, we hope our study can help motivate future studies into behavioral and demographic responses to shifting patterns of rainfall in more species so we can better anticipate the different impacts of climate change among species," Martin said.

Credit: 
The University of Montana

An improved wearable, stretchable gas sensor using nanocomposites

image: An example of a flexible gas sensor worn over a knuckle.

Image: 
Cheng Lab, Penn State

A stretchable, wearable gas sensor for environmental sensing has been developed and tested by researchers at Penn State, Northeastern University and five universities in China.

The sensor combines a newly developed laser-induced graphene foam material with a unique form of molybdenum disulfide and reduced-graphene oxide nanocomposites. The researchers were interested in seeing how different morphologies, or shapes, of the gas-sensitive nanocomposites affect the sensitivity of the material to detecting nitrogen dioxide molecules at very low concentration. To change the morphology, they packed a container with very finely ground salt crystals.

Nitrogen dioxide is a noxious gas emitted by vehicles that can irritate the lungs at low concentrations and lead to disease and death at high concentrations.

When the researchers added molybdenum disulfide and reduced graphene oxide precursors to the canister, the nanocomposites formed structures in the small spaces between the salt crystals. They tried this with a variety of different salt sizes and tested the sensitivity on conventional interdigitated electrodes, as well as the newly developed laser-induced graphene platform. When the salt was removed by dissolving in water, the researchers determined that the smallest salt crystals enabled the most sensitive sensor.

"We have done the testing to 1 part per million and lower concentrations, which could be 10 times better than conventional design," says Huanyu Larry Cheng, assistant professor of engineering science and mechanics and materials science and engineering. "This is a rather modest complexity compared to the best conventional technology which requires high-resolution lithography in a cleanroom."

Ning Yi and Han Li, doctoral students at Penn State and co-authors on the paper in Materials Today Physics, added, "The paper investigated the sensing performance of the reduced graphene oxide/moly disulfide composite. More importantly, we find a way to enhance the sensitivity and signal-to-noise ratio of the gas sensor by controlling the morphology of the composite material and the configuration of the sensor-testing platform. We think the stretchable nitrogen dioxide gas sensor may find applications in real-time environmental monitoring or the healthcare industry."

Credit: 
Penn State

Rare encounters between cosmic heavyweights

image: SDSS J141637.44+003352.2, a dual quasar at a distance for which the light reaching us was emitted 4.6 billion years ago. The two quasars are 13,000 light years apart on the sky, placing them near the center of a single massive galaxy that appears to be part of a group, as shown by the neighboring galaxies in the left panel. In the lower panels, optical spectroscopy has revealed broad emission lines associated with each of the two quasars, indicating that the gas is moving at thousands of kilometers per second in the vicinity of two distinct supermassive black holes. The two quasars are different colors, due to different amounts of dust in front of them.

Image: 
Silverman et al.

Maunakea, Hawaii - A cosmic dance between two merging galaxies, each one containing a supermassive black hole that's rapidly feeding on so much material it creates a phenomenon known as a quasar, is a rare find.

Astronomers have discovered several pairs of such merging galaxies, or luminous "dual" quasars, using three Maunakea Observatories in Hawaii - Subaru Telescope, W. M. Keck Observatory, and Gemini Observatory.

These dual quasars are so rare, a research team led by the Kavli Institute for the Physics and Mathematics of the Universe at the University of Tokyo estimates only 0.3% of all known quasars have two supermassive black holes that are on a collision course with each other.

The study is published in the August 26, 2020 issue of the Astrophysical Journal.

"In spite of their rarity, they represent an important stage in the evolution of galaxies, where the central giant is awakened, gaining mass, and potentially impacting the growth of its host galaxy," said Shenli Tang, a graduate student at the University of Tokyo and co-author of the study.

Quasars are one of the most luminous, energetic objects known in the universe, powered by supermassive black holes that are millions to billions times more massive than our Sun. As material swirls around a black hole at the center of a galaxy, it is heated to high temperatures, releasing so much light that the quasar can outshine its host galaxy.

This makes a merging pair of galaxies with quasar activity hard to detect; it is difficult to separate the light from the two quasars because they are in such close proximity to each other. Also, observing a wide enough area of the sky to catch these rare events in sufficient numbers is a challenge.

To overcome these obstacles, the team took advantage of a sensitive wide survey of the sky using the Hyper Suprime-Cam (HSC) camera on the Subaru Telescope.

"To make our job easier, we started by looking at the 34,476 known quasars from the Sloan Digital Sky Survey with HSC imaging to identify those having two (or more) distinct centers," said lead author John Silverman of the Kavli Institute for the Physics and Mathematics of the Universe. "Honestly, we didn't start out looking for dual quasars. We were examining images of these luminous quasars to determine which type of galaxies they preferred to reside in when we started to see cases with two optical sources in their centers where we only expected one."

The team identified 421 promising cases. However, there was still the chance many of these were not bona-fide dual quasars but rather chance projections such as starlight from our own galaxy. Confirmation required detailed analysis of the light from the candidates to search for definitive signs of two distinct quasars.

Using Keck Observatory's Low Resolution Imaging Spectrometer (LRIS) and Gemini Observatory's Near-Infrared Integral Field Spectrometer, Silverman and his team identified three dual quasars, two of which were previously unknown. Each object in the pair showed the signature of gas moving at thousands of kilometers per second under the influence of a supermassive black hole.

The newly-discovered dual quasars demonstrate the promise of wide-area imaging combined with high-resolution spectroscopic observations to reveal these elusive objects, which are key to better understanding the growth of galaxies and their supermassive black holes.

Credit: 
W. M. Keck Observatory

Stop! Grand theft water

An international team of researchers led by the University of Adelaide has developed a new method to better understand the drivers of water theft, a significant worldwide phenomenon, and deterrents to help protect this essential resource.

In a paper published in Nature Sustainability, researchers developed a novel framework and model, which they applied to three case studies: in Australia, the US and Spain.

Lead author, Dr Adam Loch, Senior Lecturer at the University of Adelaide's Centre for Global Food and Resources, said that water theft is a research topic that has not received a lot of coverage due to a lack of data and because often those stealing water are poor, vulnerable and at risk in developing countries.

"But theft also occurs in the developed world, especially in agricultural settings," said Dr Loch.

"According to Interpol, thieves steal as much as 30-50 per cent of the world's water supply annually - a big number.

"Compounding this problem is the fact that, as the scarcity of our most precious resource increases due to climate and other challenges, so too do the drivers for water theft."

Drivers to water theft include social attitudes, institutions and future supply uncertainty.

With the novel framework and model, water managers can test the impact of changes to detection, prosecution and conviction systems, and accurately measure the effectiveness of current penalties which may not provide an effective deterrent.

"If users are motivated to steal water because it is scarce, and they need it to keep a crop alive, then the opportunity cost of that water may far exceed the penalty, and theft will occur," said Dr Loch.

The case studies also provide evidence that where authorities fail to support detection and prosecution theft will increase, and stronger deterrents may be needed to dissuade users from stealing water to maximise profits.

"In Spain regulators were assaulted by users when they tried to stop them from stealing water; in the US marijuana growers stole water from fire hydrants and the police felt powerless to do anything about it," said Dr Loch.

Researchers said there are many cases of water theft that could be studied using the framework and model - and they encourage institutions to use the free tools located within the paper's supplementary materials.

"Much of the world's focus right now is on water efficiency investments, which might achieve (at best) between 10-20 per cent savings for water managers. But if we can recover 30-50% of 'lost' water, targeting those who steal for profit making, then that would be good for our water supply, and good for us," said Dr Loch.

Credit: 
University of Adelaide

From photons to feelings: Researchers reveal a color palette in brain

image: A. Visible wavelengths of electromagnetic radiation are not intrinsically colored. Cone cells in the retina can convert spectral information into neural signals, and these signals are further processed by the visual brain to ultimately create color perception. How color signals are processed through serial cortical stages is poorly understood; B. By applying multiple techniques, researchers charted and analyzed hue maps across three successive cortical areas - V1, V2 and V4; C. This comparative sudy reveals the brain's hue-maps develop hierarchically from cone-activation signals to isotropic hue representation, better reflecting the perceptual color space.

Image: 
CEBSIT

A recent study published in Neuron described in greater detail than ever before the anatomical embodiment of color sensations in the cerebral cortex, linking brain structure to perceptual function.

This discovery was the fruit of cooperative work between researchers in Dr. WANG Wei's lab at the Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology of the Chinese Academy of Sciences, State Key Laboratory of Neuroscience, and Dr. TANG Shiming's lab at Peking University.

Color is often found at the center of philosophical debates about the nature of conscious experience, mainly because color, more than any other sensation, illustrates that all perception is a mental creation. As realised early in the 18th century by Isaac Newton, visible wavelengths of electromagnetic radiation are not intrinsically colored; all the thousands of different hues we can recognize are simply arbitrary tags devised by the brain to represent various spectral compositions of light across the retinal image.

More technically, the outputs of retinal photoreceptors that discriminate wavelengths are combined and processed to eventually generate a perceptual color space. Color signals are processed through multiple neural stages in the deep brain; however, how our brains transform quantum-level events in photoreceptors to yield the many thousands of different hues we see every day is poorly understood.

To address this question, researchers in Drs. WANG and TANG's labs applied multiple techniques capable of imaging macaque brain activity at different scales and levels of resolution across successive processing stations in the cortex known as areas V1, V2 and V4. The aim of their study was to examine hierarchical changes in the patterns of activity when these areas process exactly the same color pattern.

The imaging methods reveal "hue maps," i.e., color palettes in the brain, spectrally organized arrangements of multiple hue responses. Figuratively, they can be thought of as rainbows of various conformations that are scattered across the brain surface.

The novel findings of this study arise from the fine structure of these hue maps. In V1, red and blue hues predominate, but this pattern of so-called "endspectral" dominance recedes in V2 and is nearly absent in V4. Essentially, the brain's hue maps develop hierarchically toward the uniformity of the perceptual hue map.

Computationally, the brain appears to be progressively integrating two distinct classes of cone-opponent signals originating in the retina. The information defining the precise hue of any given light is thus present in V1, coded by the ratio of activity between cone-opponent inputs - but it is not perceptible until it undergoes combinatorial processing by single neurons in area V4 and higher processing stations.

In summary, this comparative study reveals a progressive integration from cone-activation signals to isotropic hue representation along the visual hierarchy upon which our perceptual color space is built.

Credit: 
Chinese Academy of Sciences Headquarters

Planetary ball-milling helps protect our planet from plastics pollution

image: Functions of the supramolecular materials. When the materials were wounded, they healed within 1 min. Further, when applied as a coating on a glass substrate, the material showed extremely fast healing properties, like skin. The recyclable property can treat severe damage which cannot be treated by the self-healing property. This extends the lifetime of the material.

Image: 
Osaka University

Osaka, Japan - Plastics are ubiquitous in modern life; unfortunately, once they lose function, they pollute the environment. Now, researchers at Osaka University have developed polymer materials that combine self-healing with strength and recyclability that could extend the functional lifetimes of manufactured plastics, thus minimizing the surging problem of discarded remnants.

Polymers are versatile substances, composed of many repeating molecular subunits, with essential and diverse functions in biological processes and industry. Sadly, their durability is double-edged: waste plastics generate litter and can contaminate our environment for centuries. About 50 kg of plastics is produced annually for every human; this doubles every decade. By the year 2050, there may be more plastics in our oceans than fish. As plastics are indispensable, extending their functional life by enhancing durability, self-healing and recyclability can help reduce waste.

Host-guest interactions, a fascinating branch of supramolecular chemistry, describes molecular complexes held in unique structural relationships by non-covalent bonding. These physical linkages allow molecular recognition and are ideal for preparing materials with rapidly reversible properties.

"We prepared supramolecular materials by mixing host and guest polymers of acetylated β-cyclodextrin and adamantane," explains Junsu Park, lead author. "We compared three mixing methods: conventional casting, planetary kneading and ball-milling. Ball-milling employs zirconia balls in a zirconia grinding jar on a sun-wheel revolving eccentrically in reverse. The additional rotational forces on the grinding surfaces and the interplay between impact and friction cause nanoscale mixing."

The researchers analyzed the polymers by wounding, re-joining, as coating of a glass substrate and after repeated ball-milling. Using dynamic mechanical analysis, thermal property measurements, small angle X-ray scattering measurements, and confocal laser scanning microscopy, etc they assessed scratch resistance, deformability and tensile strength.

The results were remarkable. Planetary mixing efficiently produced tough, self-healable, and recyclable supramolecular materials. Surface scratches disappeared in seconds and fractured fragments united in minutes. Moreover, mechanical properties were preserved even after repeated milling. "Ball-milling disentangles the polymer chains in the materials and increases their mobility while facilitating their re-formation," Park explains. "This maintains the number of host-guest interactions, ensuring both self-healing and toughness."

Senior author Yoshinori Takashima describes the potential of these discoveries: "We can develop tough materials capable of self-repair that retain these properties even when recycled. Prolonging their functional lifespan is key to saving the environment as they are being increasingly deployed in manufacture. Additionally, their unique biomimetic properties open up avenues of application in fields such as artificial skin for prostheses, robots and even vehicles."

Credit: 
Osaka University

New study takes aim at advanced types of non-addictive pain therapies

image: Heat activates the TRPV1 channel which is in the middle. In red, is the domain the authors show to be central to heat activation, the molecule on the right is capsaicin. It is the cognate agonist for TRPV1, it is also the active ingredient in spicy food and pepper/bear spray. In the end TRPV1 integrates these stimuli which sends the signals to the brain for interpretation (i.e. TRPV1 is the receptor that initiates signal transduction).

Image: 
Wade Van Horn

A team of scientists from ASU's School of Molecular Sciences and the Biodesign Institute have recently published a study in Nature Communications that helps clarify the contributions to an ion channel's temperature - dependent activation. This in turn should aid in the development of new types of non-addictive pain therapies.

The ability to sense and respond to temperature is fundamental in biology. Ion channels are formed by membrane proteins that allow ions to pass through the otherwise impermeable lipid cell membrane, where they are used as a communication network.

"TRPV1 is an ion channel that is widely expressed in various tissues and plays a variety of roles in biology," explains SMS professor Wade Van Horn, senior author of the current research. "It is best known for its role as the primary hot sensor in humans; it is the main way that we sense heat in our environment."

Although important contributions have been made in the investigation of TRPV1 thermosensing, its mechanism has remained elusive.

TRPV1 is also a common taste and pain sensor, think spicy foods and pepper spray. Beyond these roles, it has been implicated in longevity, inflammation, obesity, and cancer. For decades it has been a target in the search for new types of pain medication, ones that are not addictive.

"However, to date, a common feature is that while TRPV1 targeting compounds can relieve pain, they also cause off-target effects, especially causing changes in body temperature, which has limited their utility. These off-target effects happen because TRPV1 is activated by many distinct stimuli, including ligands (i.e., capsaicin - the main ingredient in pepper spray), heat, and protons (acidic pH)," says Van Horn.

Also particularly limiting, is the uncertainty about the mechanisms that underlie temperature-sensing and how the different activation mechanisms are linked together.

This study used a variety of techniques, from cellular to atomic in nature, to investigate the domain of TRPV1 that is key to its ligand activation.

The techniques included Nuclear Magnetic Resonance spectroscopy experiments (like an MRI) aided by Brian Cherry (Associate Research Professional in the Magnetic Resonance Research Center), intrinsic fluorescence carried out in SMS associate professor Marcia Levitus' lab. Levitus is also part of the Biodesign Center for Single Molecule Biophysics. Other techniques included far ultraviolet circular dichroism and temperature dependent electrophysiology.

Van Horn explains that this work identifies for the first time, both functionally and thermodynamically, that a particular region (of TRPV1) is crucial to heat activation. The team proposes, and provides experimental validation for, the heat activation mechanism and details a number of structural changes that happen as the temperature is changed.

This study provides a framework that the team anticipates will be foundational for future studies to further refine how we sense high temperatures and, importantly, how we can distinguish and target specific activation mechanisms that should promote the development of new types of non-addictive pain therapies.

All the interdisciplinary studies were completed at ASU. The team also included: Minjoo Kim, Nicholas Sisco and Jacob Hilton who are currently postdoctoral researchers at Columbia University, Barrow Neurological Institute and NIH respectively. Camila Montano and Wade Van Horn, are also part of the Biodesign Institute Virginia G. Piper Center for Personalized Diagnostics and Manuel (Mac) Castro is currently a doctoral student at Vanderbilt University.

Credit: 
Arizona State University

New Cretaceous Jehol fossil sheds light on evolution of ancestral mammalian middle ear

image: Reconstruction of Sinobaatar pani

Image: 
IVPP

A joint research team led by Dr. MAO Fangyuan from the Institute of Vertebrate Paleontology and Paleoanthropology (IVPP) of the Chinese Academy of Sciences and Prof. MENG Jin from the American Museum of Natural History has reported a new multituberculate mammal, Sinobaatar pani, with well-preserved middle ear bones.

The new mammal comes from the Early Cretaceous Jehol Biota in Northeast China. Comparing three types of fossils with extant mammals at different embryological stages, the researchers identified various evolutionary stages and ancestral phenotypes of the mammalian middle ear.

Their findings were published in National Science Review on Aug. 25.

For mammals, the external ear (the pinna) collects airborne sounds that vibrate the eardrums, and the middle ear bones on the inner side of the eardrum function as a delivery system that transmits sound vibrations to the inner ear.

According to previous studies, we know that the extra mammalian ear bones actually originated from the jawbones of reptiles. However, few studies have actually looked at the detailed morphologies of ear bones that are the ancestral phenotypes for the middle ear of modern mammals.

Multituberculates are an extinct group of mammals that lived from the Middle Jurassic (about 165 million years ago) to the Eocene (about 35 million years ago). The most exciting discovery about the new animal is its middle ear bones, which are the first unequivocal evidence of the five auditory bones from this extinct mammalian group.

These miniscule bones are still embedded in rock and not visible. Using computerized tomography (CT), MAO and her colleagues were able to digitally "extract" the ear bones from the rock and reconstruct them in three-dimensional form so that their morphology could be observed in detail.

The data provided by MAO and her colleagues are by far the best evidence of middle ear morphology in known Mesozoic mammals. For comparison, the data also included similar CT reconstructions of the middle ear of extant monotremes, marsupials and placentals.

"There are two basic patterns of the middle ear in living mammals, represented by monotremes and therians, respectively. In the former, the middle ear is characterized by an 'abutting contact' between the incus and malleus, which is distinct from the one in therian mammals where the incus-malleus articulation is saddle-shaped," said Dr. MAO.

The researchers recognized that the three main Mesozoic mammalian groups (i.e., multituberculates, eutriconodontans, and symmetrodontans) share a similar middle ear structure between the incus and malleus, which they termed the "braced hinge joint".

Although they acknowledged that the middle ear may have evolved independently in several mammalian groups, they proposed that the braced hinge joint could represent a critical feature of the ancestral phenotype of the mammalian middle ear.

The abutting pattern in monotremes and the saddle-shaped joint in therians may well be derived from the braced hinge joint linking the incus and malleus as observed in Mesozoic mammals. At the least, these fossil forms have narrowed the morphological gap between the middle ear of mammal-like reptiles, formed by the postdentary bones lodged in the lower jaw, to the middle ear of extant mammals.

The researchers proposed that the surangular bone, which is another postdentary bone in mammal-like reptiles, persisted in Mesozoic mammals; its fate in living mammals remains uncertain.

They further showed that middle ear morphologies in Mesozoic mammals represent different evolutionary stages, with that of Liaocodondon being the most primitive, Origolestes the intermediate, and Sinobaatar the most advanced.

Developmental features observed in extant mammals and evolution of the mammalian middle ear in fossil records are correlated, said MAO.

Credit: 
Chinese Academy of Sciences Headquarters

Study finds association between nightmares and heart disease in veterans

DARIEN, IL - A new study found a surprising association between frequent and severe nightmares and cardiovascular disease in veterans, even after controlling for post-traumatic stress disorder.

Preliminary results show that 32% of veterans reported having frequent nightmares and 35% reported severe nightmares over the past week. Frequent and severe nightmares were associated with heart problems, high blood pressure, and heart attack after adjusting for age, sex and race. Associations between nightmares and high blood pressure and heart problems remained significant after controlling for PTSD diagnosis, depression diagnosis and status as a smoker.

"Our cross-sectional findings set the stage for future research examining the possibility that nightmares may confer cardiovascular disease risks beyond those conferred by PTSD diagnosis alone," said principal investigator Christi Ulmer, who has a doctorate in clinical psychology and is a clinical research psychologist at the Durham VA Health Services Research and Development ADAPT Center and assistant professor in the Department of Psychiatry and Behavioral Sciences at Duke University Medical Center. "If longitudinal research demonstrates a causal role for nightmares in cardiovascular disease risk, nightmare treatment could be a strategy for improving cardiovascular health."

The study involved 3,468 veterans with an average age of 38 years. Nightmare frequency and severity was assessed using the Davidson Trauma Scale, with nightmares classified as "frequent" if they occurred at least 2 to 3 times per week and severe if they were at least moderately distressing. Medical problems were assessed using a medical questionnaire, and PTSD and depression diagnoses were established using a clinical interview. Thirty percent of participants met criteria for current PTSD.

The research was supported by the VISN 6 Mental Illness Research, Education and Clinical Center (MIRECC) and the Department of Veterans Affairs HSR&D ADAPT Center at the Durham VA Health Care System.

The research abstract was published recently in an online supplement of the journal Sleep and will be presented as a poster Aug. 28-30 during Virtual SLEEP 2020. SLEEP is the annual meeting of the Associated Professional Sleep Societies, a joint venture of the American Academy of Sleep Medicine and the Sleep Research Society.

Credit: 
American Academy of Sleep Medicine

The patients left behind by HIV research

People with HIV from BAME communities, women and heterosexual men are underrepresented in HIV studies - according to new research from the University of East Anglia and Western Sydney University.

Medication to manage HIV is now very effective at keeping people well. But over half of people living with HIV do not take their medication as prescribed.

We are yet to find solutions that are routinely used by healthcare teams to successfully support people to take their medication as prescribed - despite many studies designed to investigate the problem.

New research published today reveals that the problem could be in the way that studies are designed in the first place - with BAME communities, women and straight men under-represented.

The research team say that this imbalance of representation needs to be fixed, in order to design solutions that suit the needs of a diverse population and keep people with HIV living longer, healthier lives.

Lead researcher Prof Debi Bhattacharya from UEA's School of Pharmacy said: "It's really important that people with HIV start taking medication as soon as possible and continue taking it as prescribed for life. While medication can't cure HIV, taking it correctly helps people live longer, healthier lives. Medication can also reduce the risk of HIV transmission.

The research team reviewed 80 studies designed to evaluate different approaches for supporting people to take their HIV medication correctly.

They found that people from ethnic minorities, women and heterosexual men were underrepresented for the country in which the study was taking place.

Prof Bhattacharya said: "We found that none of the 80 studies had a trial population that reflected the actual population of people living with HIV.

"For example in many cases, gay men were over-represented in studies, compared with the amount of gay men living with HIV.

"In one American study not a single woman was included even though women represent around one in five people with HIV."

"This is a problem because we know that in several countries including America, HIV rates in men are falling more than they are for women."

"As these patient groups are being significantly underrepresented in these types of trials, their needs, beliefs and attitudes to treatment are not fully understood. This potentially leaves these populations without the support they need to live well with HIV.

"We also know that language profoundly affects the way patients understand their treatment routines - which impacts on how they engage with their disease and medication. Failure to take this into account seriously hinders people from getting the best clinical outcomes.

"We found that none of the studies used research methods to encourage people with differing languages and culture to contribute in the ways that are needed for the research to be successful.

"This may explain why we have seen few of these solutions that are shown to work in the studies then go on to be routinely used in healthcare.

"Over the years we have seen greater scrutiny over how research is conducted to ensure that people invited to participate in research are fully informed before they decide to participate. These changes, like making sure that we have written consent, have been very important for protecting the public.

"But, the changes have led to new problems, such as people with limited literacy or those less fluent in the local language being excluded from studies. It is important that we continue to protect the public whilst also supporting people with differing needs to participate in research."

"The guidelines for carrying out research need to recognise that research methods must be adapted to support the wide range of people with differing needs that make up the diversity of people with a specific disease.

"The guidelines also need to communicate more strongly, the importance of properly involving people for whom the research is intended to help, at the earliest possible stage of the research otherwise these health inequalities may continue."

Credit: 
University of East Anglia

New analysis shows hydroxychloroquine does not lower mortality in COVID-19 patients, and is associated with increased mortality when combined with the antibiotic azithromycin

A new meta-analysis of published studies into the drug hydroxychloroquine shows that it does not lower mortality in COVID-19 patients, and using it combined with the antibiotic azithromycin is associated with a 27% increased mortality. The study is published in Clinical Microbiology and Infection, the official journal of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID).

"This meta-analysis shows that hydroxychloroquine alone is not effective for the treatment of COVID-19 patients and that the combination of hydroxychloroquine and azithromycin increases the risk of mortality," say the authors who include Thibault Fiolet, Center for Research in Epidemiology and Population Health, INSERM, Institut Gustave Roussy and Paris-Sud 11 University/Paris-Saclay University, Paris, France. "These data support current clinical recommendations such as those of the US National Institutes of Health (NIH) which do not recommend the use of hydroxychloroquine alone or in combination with azithromycin for COVID-19 patients."

Chloroquine is used to prevent and treat malaria, while hydroxychloroquine is a less toxic metabolite of chloroquine and is used to treat rheumatic diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) and Sjogren's syndrome. Hydroxychloroquine in particular has received extensive media coverage since the outbreak of the SARS-CoV-2 pandemic as a potential treatment for COVID-19. Azithromycin is used to treat a wide range of bacterial infections, but has also been promoted as a potential treatment for COVID-19 due to its alleged antiviral or anti-inflammatory properties.

In this new analysis, the authors searched for studies that assessed chloroquine or hydroxychloroquine with or without the antibiotic azithromycin. The authors found 29 articles that met their criteria, all except one of which were conducted on hospitalised patients and evaluated the effects of hydroxychloroquine with or without azithromycin.

Among the 29 articles, 3 were randomised controlled trials, one was a non-randomised trial and 25 were observational studies, including 11 with a 'critical' risk of bias and 14 with a 'serious or moderate' risk of bias*. After excluding studies with a critical risk of bias, the meta-analysis included 11,932 patients in the hydroxychloroquine group, 8,081 in the hydroxychloroquine with azithromycin group and 12,930 in the control group (who received neither drug).

The results showed that hydroxychloroquine was not associated with mortality, either in all trials combined, or in separate analyses of randomised controlled trials or observational studies. The relative risk of death for use of hydroxychloroquine was 17% lower than controls for all studies combined, but 9% higher in randomised controlled trials. In both cases, these results were not statistically significant.

However, the combination of hydroxychloroquine and azithromycin in patients with COVID-19 was associated with a statistically significant 27% increase in mortality compared with controls. The authors say: "These results confirm the preliminary findings of several observational studies which have shown that the combination of hydroxychloroquine and azithromycin might increase the risk of acute, life-threatening cardiovascular events."

The authors discuss limitations of their work which include the differing levels of COVID-19 disease severity across patients and also the actual definition of severity. Furthermore, most of the studies included were observational studies (not designed to find a causal relationship). Finally, this meta-analysis did not include results from the European DisCoVeRy trial and the WHO Solidarity trial that are not yet published or communicated (but both have already discontinued their hydroxychloroquine arms).

The authors conclude: "There is already a great number of studies that have evaluated hydroxychloroquine alone or in combination and it seems unlikely at this stage that any efficacy will ever emerge. Our results suggest that there is no need for further studies evaluating these molecules, and the European DisCoveRy and WHO international Solidarity clinical trials have already discontinued treatment arms using hydroxychloroquine."

Credit: 
European Society of Clinical Microbiology and Infectious Diseases

How vitamin C could help over 50s retain muscle mass

Vitamin C could be the key to better muscles in later life - according to new research from the University of East Anglia (UEA).

A study published today shows that older people who eat plenty of vitamin C - commonly found in citrus fruits, berries and vegetables - have the best skeletal muscle mass.

This is important because people tend to lose skeletal muscle mass as they get older - leading to sarcopenia (a condition characterised by loss of skeletal muscle mass and function), frailty and reduced quality of life.

Lead researcher Prof Ailsa Welch, from UEA's Norwich Medical School said: "As people age, they lose skeletal muscle mass and strength.

"People over 50 lose up to one per cent of their skeletal muscle mass each year, and this loss is thought to affect more than 50 million people worldwide."

"It's a big problem, because it can lead to frailty and other poor outcomes such as sarcopenia, physical disability, type-2 diabetes, reduced quality of life and death."

"We know that Vitamin C consumption is linked with skeletal muscle mass. It helps defend the cells and tissues that make up the body from potentially harmful free radical substances. Unopposed these free radicals can contribute to the destruction of muscle, thus speeding up age-related decline."

"But until now, few studies have investigated the importance of Vitamin C intake for older people. We wanted to find out whether people eating more Vitamin C had more muscle mass than other people."

The research team studied data from more than 13,000 people aged between 42-82 years, who are taking part in the EPIC (European Prospective Investigation into Cancer and Nutrition) Norfolk Study.

They calculated their skeletal muscle mass and analysed their vitamin C intakes from a seven-day food diary. They also examined the amount of vitamin C in their blood.

Dr Richard Hayhoe, also from UEA's Norwich Medical School, said: "We studied a large sample of older Norfolk residents and found that people with the highest amounts of vitamin C in their diet or blood had the greatest estimated skeletal muscle mass, compared to those with the lowest amounts.

"We are very excited by our findings as they suggest that dietary vitamin C is important for muscle health in older men and women and may be useful for preventing age-related muscle loss.

"This is particularly significant as Vitamin C is readily available in fruits and vegetables, or supplements, so improving intake of this vitamin is relatively straightforward.

"We found that nearly 60 per cent of men and 50 per cent of women participants were not consuming as much Vitamin C as they should, according to the European Food Safety Agency recommendations.

"We're not talking about people needing mega-doses. Eating a citrus fruit, such as an orange, each day and having a vegetable side to a meal will be sufficient for most people."

Credit: 
University of East Anglia