Culture

Bird brains are surprisingly complex

image: The fiber structure of pigeons and various mammals in comparison. The 3D-PLI method shows the directions of the nerve fibers color-coded. The depictions seen here do not reflect the true sizes - a human brain is about 500 times larger than pigeon brain.

Image: 
Copyright: HHU Düsseldorf / Herold et al.

Some birds can achieve extraordinary cognitive performance - but their brains were considered to be rather disorganized compared to those of mammals. Scientists from Bochum (RUB), Düsseldorf (HHU), Jülich (FZJ), and Aachen (RWTH), now for the first time, show striking similarities between the neocortex of mammals and sensory brain areas of birds: Both are wired in horizontal layers and vertical columns. The finding refutes 150-year-old assumptions. Decisive insights were provided by a method developed by Jülich and Düsseldorf brain researchers. The results have been published this week in the journal "Science".

Birds and mammals have the largest brains relative to their body size. Otherwise they have little in common, so the assumption of scientists for more than hundred years: Mammalian brains have a cerebral cortex that is made up of six horizontal layers and columns that run perpendicular to these layers. The avian brain in contrast appears to be poorly organized at first glance, and only shows accumulations of cells with more or less density.

"In view of the astonishing cognitive performance that birds can achieve, however, it was suspected that their brain is higher organized than previously assumed," says Prof. Dr. Onur Güntürkün, head of the Biopsychology work unit at the Faculty of Psychology at the RUB and an expert on the cognition of birds.

Indeed, researchers around Dr. Christina Herold (C. and O. Vogt Institute for Brain Research, HHU) and Dr. Martin Stacho (RUB) have now succeeded in proving that the brains of birds and mammals look surprisingly similar in their organization.

The fibers in the bird brain run horizontally and vertically, just like in the neocortex of mammals.

Previously, it was not possible to map the fiber structure of larger areas of the avian brain with the required accuracy. Commonly used techniques are either limited to small tissue samples or lack resolution and sensitivity to reveal microstructural features that define the brain's neuronal organization. The level in between therefore remained in the dark.

"3D PLI has a slightly lower resolution than tracing methods, but is capable of analyzing large tissue volumes in a reasonable time - a decisive advantage," explains Dr. Markus Axer, head of the fibre architecture group at the Forschungszentrum Jülich. Using this method, the researchers were able to analyze three complete pigeon brains at a resolution of 1.3 micrometers (millionths of a millimeter). Per brain, 250 sections were scanned at high resolution and reconstructed in 3D.

"3D PLI is a technique that contributes significantly to a deeper understanding of the brain's connectivity and makes it possible to identify similarities and differences in neuronal networks across species," emphasizes Prof. Katrin Amunts, Director of the two institutes in Jülich and Düsseldorf.

Because the method is computationally very challenging, the researchers use the FENIX supercomputing platform, to process the data. FENIX is a European network of High Perfomance Computing Centers that includes Jülich Supercomputing Centre, and is part of the new EBRAINS infrastructure developed by the Human Brain Project. EBRAINS provides neuroscientists worldwide with a set of advanced new methods and resources, including the 3D atlases of the human brain, BigBrain and Julich-Brain, which were created in Jülich and Düsseldorf.

Further tracing experiments in Bochum made it possible to examine the cross-linking of cells in the bird brain in detail. The technique uses tiny crystals that spread into the smallest branches of the nerve cells in brain slices. "Here, similarly, the structure was shown to consist of columns in which signals are transmitted from top to bottom and vice versa, and long fibers running horizontally," explains Onur Güntürkün. However, this structure is only found in the sensory areas of the bird brain. Other areas, such as associative areas, are organized differently.

Credit: 
Forschungszentrum Juelich

MarrowQuant: A new digital-pathology tool

image: A screenshot of MarrowQuant annotating a bone marrow trephine biopsy from a patient surfing from chemotherapy-induced aplasia.

Image: 
Olaia Naveiras (EPFL)

The bone marrow is the soft tissue inside our bones. Its main role is to produce stem cells that will go on to become various cells of the blood, including white blood cells that fight infections, red blood cells that carry oxygen throughout the body, and platelets that control bleeding.

But the bone marrow also contains fat cells, the adipocytes, which were for a long time thought of as "passive fillers" of the marrow cavity. In recent years, however, bone marrow adipocytes have been shown to carry out a far more important role within the microenvironment of the bone marrow than initially thought.

The ratio between blood-forming cells (red color) and adipocytes (yellow color) is not constant. It changes with age, between different parts of the skeleton, and in various disease conditions or cancer treatments like chemo- and radio-therapy, which cause a condition called "bone marrow aplasia". Changes in the cells' ratio produce so-called "yellow-to-red" and "red-to-yellow" shifts in the color of the bone marrow, which is used for monitoring its condition.

This monitoring however is not entirely standardized, but relies on assessments by pathologists of histological images. In research, the relative health of bone marrow samples is also assessed qualitatively, through histological images. This subjectivity, although greatly compensated for, can still cause diagnostic and research limitations.

Publishing in Frontiers Endocrinology, scientists led by Olaia Naveiras at EPFL, introduce MarrowQuant, a new digital pathology software that can "read" histological images of bone marrow and "describe" them quantitatively, building maps based on values to complement the images. The potential applications of this approach can revolutionize digital histology.

Its code already uploaded on GitHub, MarrowQuant is described as "a user-friendly algorithm for the quantification of H&E bone marrow tissue biopsies in whole slide images."

In the paper, the researchers use MarrowQuant to build the first-ever quantitative map of the heterogeneity of bone marrow throughout the skeleton of mice suffering from age-induced and radiation-induced aplasia.

"The work was a massive effort only possible thanks to the long and fruitful collaboration with EPFL's BioImaging and Optics Platform [BIOP]," says Naveiras who is also the President of the International Bone Marrow Adiposity Society (BMAS).

MarrowQuant, uses the open-source software QuPath, and can systematically quantify multiple bone components in histological images without bias. It does this by discerning and quantifying the areas occupied by various parts of the bone marrow - including the vasculature and the bone itself.

One of the potential uses of MarrowQuant will be to re-examine historical sample collections of bone samples and even data from old clinical trials.

"MarrowQuant has already been extremely well received by the digital pathology community," says Naveiras. "Moreover, the very selective Image Database Resource (IDR) has selected the associated dataset for publication, which includes over 300 annotated images."

Professor Olaia Naveiras' lab is part of EPFL's Swiss Institute for Experimental Cancer Research (ISREC), situated in the School of Life Sciences.

Credit: 
Ecole Polytechnique Fédérale de Lausanne

The cost of drought in Italy

Droughts are, after floods and storms, the costliest natural hazard. The expected increa,se in the frequency and intensity of drought events due to climate change reinforces the necessity to improve the quality and reliability of information about the economic impacts of droughts and the need for more accurate cost analyses to embed these estimates into the assessment of the costs of climate change.

A new study realized with the contribution of the CMCC Foundation, recently published on Land Use Policy, proposes a novel method to assess the overall economic effects of agricultural droughts using a coupled agronomic-economic approach that accounts for the direct and indirect impacts of this hazard in the economy.

"Our results reveal", commented researcher David García-León, lead author of the study, "over the period analyzed, droughts of different severity hit Italy and drought-induced economic losses ranged in Italy between 0.55 and 1.75 billion euros".

David García-León, who was Marie Sk?odowska-Curie Postdoctoral Fellow at CMCC@Ca'Foscari Division and he's now at the European Commission, Joint Research Centre, focused his research on assessing the overall macro-economic effects (% GDP) of agricultural drought impacts in Italy using a coupled CGE-econometric approach. The other authors of the study are the CMCC researchers Gabriele Standardi and Andrea Staccione, respectively working at CMCC Divisions ECIP - Economic analysis and Climate Impacts and Policy and RAAS - Risk Assessment and Adaptation Strategies.

In this study, the authors focused on agricultural droughts, which represent the impact on crop yields. "We used a satellite-based indicator of agricultural drought, the vegetation indicator fAPAR - fraction of Absorbed Photosynthetically Active Radiation -", Dr. García-León explains, "to detect and monitor the impacts on vegetation growth and productivity of environmental stress factors, especially plant water stress due to drought".

"This data", CMCC researcher Andrea Staccione adds, "have been then correlated with the geo-referenced data of land use and agricultural production at the farm-level provided by the Italian Council for Agricultural Research and Economics (Consiglio per la Ricerca in agricoltura e l'analisi dell'Economia Agraria - CREA) in order to assess the direct impacts of agricultural droughts on crop productivity."

The study distinguished between three types of drought severity levels (mild, moderate and extreme), and three representative years of each state were selected to describe each scenario: solar years 2003, 2006 and 2011 were studied as extreme, moderate and mild dry years, respectively. After the estimation of the direct impacts of droughts on crop yields using statistical models calibrated for each crop, the authors estimated the indirect impacts at the sectoral, regional and country-wide level. "Local-level, crop-dependent productivity shocks were fed into a regionalised Computable General Equilibrium model specifically calibrated for the Italian economy", CMCC researcher Gabriele Standardi explains. "Our estimates indicate that the total damages caused by agricultural droughts in the Italian economy can range from 0.01?0.10% of Italian GDP, that is, from approximately EUR 0.55 to EUR 1.75 billion. These damages concentrate but extend beyond the agricultural sector, with substantial identified impacts on food industry manufacturing and wholesale and trade services". This estimated overall effect on GDP is coherent with other outcomes obtained in different studies and, in particular, the agricultural production loss identified under severe drought conditions (EUR 2 billion) is consistent with the figure reported by the Italian Association of farmers in 2017, considered an extreme dry year. The spatial distribution of the identified losses showed large regional heterogeneity, according to the geographical configuration of droughts in a specific year, and on the specific crops cultivated in the different areas analysed. Moreover, the simulations suggested the presence of a recomposition of land use and production, that is a land-use substitution effect from less to more drought-resistant crops following a drought (e.g. olive).

"In the end, Andrea Staccione concludes, "it's important to highlight that our approach is fully systematic and scalable and thus could be applied to more specific areas or could be expanded to implement large pan-European drought cost assessments. Our study therefore might improve policy approaches to managing drought risks, while pointing out the best pre-impact (mitigation) and post-impact (response) interventions to be included in drought plans".

The proposed methodology shows its full potential as a support to decision-making processes on land use and drought management. For example, regional risk maps could help to identify areas with the highest exposure and vulnerability. The analyses of the drought risk on specific regions could also contribute to defining insurance tools that reflect the costs produced by drought events and, consequently, appropriate compensation tools.

Credit: 
CMCC Foundation - Euro-Mediterranean Center on Climate Change

Covid-19: Social distancing is more effective than travel bans

Forecasting the spreading of a pandemic is paramount in helping governments to enforce a number of social and economic measures, apt at curbing the pandemic and dealing with its aftermath.

Now researchers present an efficient model to study and forecast the spreading dynamics and containment across different regions of the world.

- We discover that social distancing measures are more effective than travel limitations across borders in delaying the epidemic peak, says Professor of theoretical physics, Francesco Sannino, University of Southern Denmark and Danish Institute of Advanced Science, continuing:

Development in individual regions

- The results corroborate our finding that the travel across regions sparks the epidemic diffusion, which then develops in each region independently.

Virus-induced pandemics like Covid-19 are a threat to humans not only because of the number of human lives taken but also because of the profound and long-lasting impact on the economy and social dynamics.

While different empirical models already exist to describe the epidemic dynamics locally and globally, a coherent framework is missing. Using a powerful language and methodology borrowed from high energy physics, Professor Sannino and his colleague Giacomo Cacciapaglia from University of Lyon, can now study and forecast the spreading dynamics and containment across different regions of the world.

- We plan on embarking on a world-wide monitoring to make global projections that will help governments and industries make containment plans and strategize about reopening society and how to best implement border control, says Professor Sannino.

Credit: 
University of Southern Denmark

Oligomeric materials to enhance water splitting

image: oligomeric catalyst

Image: 
Marcos Gil-Sepulcre (ICIQ)

Researchers from the Llobet group have developed a new molecular material made out of oligomers and used it as a catalyst in water oxidation, achieving unprecedented current densities for molecular catalysts. The paper "Water oxidation electrocatalysis using ruthenium coordination oligomers adsorbed on multiwalled carbon nanotubes" has been published in Nature Chemistry.

The generation of electro-anodes and cathodes for water splitting devices based on molecular complexes anchored onto solid surfaces is gaining traction thanks to their versatile and modular properties through ligand design. After studying the catalytic behaviour of oligomers of general formula {[Ru(tda)(4,4'- bpy)]n(4,4'-bpy)} (where n is 1, 2, 4, 5 or 15), the scientists from ICIQ's Llobet team set out to anchor them onto graphitic surfaces. "We decided to design an oligomeric material based on our powerful Ru(tda) catalyst to move from homogeneous to heterogeneous applications. We had to anchor the catalyst on a surface to find a tangible application on water-splitting devices," explains Marcos Gil-Sepulcre, postdoctoral researcher and group coordinator at the Llobet group and first co-author of the paper.

In collaboration with international partners such as Johannes Elemans at the Institute for Molecules and Materials Radboud University and Christina Scheu at the Max-Planck-Institut fu?r Eisenforschung GmbH in Du?sseldorf, the scientists carried out multiple Microscopy studies to characterize the hybrid materials. In addition, Grazing-incidence small-angle X-ray scattering (GIWAXS) was carried out at the Alba synchrotron by Marc Malfois and Eduardo Solano. Further, Density-functional theory (DFT) calculations, conducted by the ICIQ Maseras group, to explore the nature of the interaction between the oligomers and the graphitic surfaces. X-ray absorption spectroscopic (XAS) measurements were also employed, in collaboration with the group of D. Moonshiram at IMDEA Nanociencia, to analyse the oligomers at the graphitic surfaces, and evaluate their fate during and after catalysis. This way the researchers confirmed the molecular nature of the oligomer and found out that it is adsorbed to the graphitic surface via aromatic catalyst-surface C-H-π interactions - an anchoring strategy that has never been described for molecular catalysts up to now.

A single monomer of the oligomer employed is unable to anchor because its interactions with the surface are too weak. Finding strength in numbers, once multiple units are introduced, the large number of C-H-π interactions stabilise the whole chain. The conformation of the hybrid material (a nanotube surrounded by oligomers) is the reason behind its high efficiency: all the ruthenium atoms in the oligomers are active catalytic centres - as opposed to dumping tones of oxides on electrodes as usually done in material science.

The resulting hybrid molecular material behaves as a rugged and powerful electro-anode for the water oxidation reaction achieving unprecedented current densities for molecular catalysts in the whole range of pH, but especially at neutral pH. "To our knowledge, there's no coordination polymer, MOF or COF, or organometallic material that works under neutral conditions, gives these currents and is stable," claims Gil-Sepulcre.

The work provides the basis for designing robust and efficient hybrid molecular electro-anode materials for the oxidation of water-based on Ru complexes, that can be extended to other transition metals and other catalytic reactions. The team is already working on implementing the hybrid material on photoelectrochemical cells to test its applications in a water-splitting device.

Credit: 
Institute of Chemical Research of Catalonia (ICIQ)

Wound-healing waves

video: Chemical waves of protein activation observed in a layer of cells.

Image: 
Tsuyoshi Hirashima

Many cells in our bodies are on the move and somehow seem to "know" where to go. But how do they learn the location of their destination? This question is key to understanding phenomena such as the renewal of cells in our body, the migration of cancer cells, and especially how wounds heal. Edouard Hannezo and his group at the Institute of Science and Technology Austria (IST Austria) in collaboration with Tsuyoshi Hirashima and his student at Kyoto University propose a new model of information transfer in which cells utilize long-distance traveling waves in a self-organized manner to close a wound. This study was recently published in the journal Nature Physics.

The researchers built a mathematical model to describe the interactions within a layer of cells on a substrate, similar to a layer of skin. These cells contain chemical signalers--proteins--that allow them to sense other cells around them, so whether they are pushed or pulled, and to control their own movement. What the scientists found is that the intricate interplay of cell movement, sensing of the environment, and states of protein activation within the cells combine to create coupled mechanical and chemical traveling waves in which directional information is encoded.

Feedback loops

The mechanical wave appears as denser and sparser regions of cells alternating in space and time. The chemical wave appears as protein activity and is triggered by cell movement and mechanical feedback. The cells' chemistry in turn drives cell shape changes and movement closing a feedback loop with cell mechanics. In this coupled system these mechanical and chemical waves arise spontaneously due to feedback and amplification.

In a normal unwounded layer of cells, these waves propagate without a preferred direction, but when an artificial wound is introduced on one side, waves re-orient to propagate exclusively away from the wound. The researchers thus hypothesized that the waves could be a communication tool, allowing cells very far from the wound--and thus not directly "seeing" it--to sense which way to go.

Reading the Waves

A density wave makes the neighbors of a cell push and pull on it along the direction in which the wave is traveling. Since the forces exerted on the cell are equal and opposite between the crests and troughs of each wave, the result is that the cell just moves small distances back and forth without any net motion. In effect, the cell has no way of knowing the direction the wave came from and thus has no information about the location of the wound.

This is where the second wave of protein activity comes in. It hits the cell slightly after the density wave due to the delay that it takes for proteins to activate. And because protein activity controls the speed at which the cells move, a delay between the two waves allows for cells to move quickly when being pulled in the direction of the wound, and slowly when being pushed away. In this way, cells can break symmetry and start to move in the preferred direction towards the wound.

Out-of-equilibrium Experiments

The researchers at Kyoto University observed this out-of-equilibrium behavior of wound healing during in vitro experiments with real cells on a substrate. They used a novel microscopy technique to allow them to measures protein activity within each cell: the protein was modified so that it lit up when activated thus revealing waves of protein activation propagating throughout the cell layer. The researchers were able to quantitatively predict the wave patterns, which they then also observed experimentally. More strikingly, they also found that the delay between the two waves was close to the theoretically predicted optimum for allowing cells to extract maximum information from the waves.

This mechanism of self-organization is remarkable for allowing robust and spontaneous communication of direction over large distances within cell layers. It demonstrates one way in which coordinated behavior can arise in our bodies helping them to heal and grow.

Credit: 
Institute of Science and Technology Austria

Looking at evolution's genealogy from home

image: As the developers of 2-n-way, Dr. Jürgen Schmitz, Dr. Liliya Doronina, Norbert Grundmann, Fengjun Zhang and Dr. Gennady Churakov (from left) are delighted at the publication of their project in the specialist press

Image: 
Erk Wibberg

Evolution leaves its traces in particular in genomes. Pinpointing its influence is a laborious process - but one in which Dr. Jürgen Schmitz and his team at the University of Münster are at home. Five years ago, the team made public a web app which can compare the genomes of humans and animals and thus help to provide an understanding of evolutionary developments. The Münster researchers are now going one step further: their new software - "2-n-way" - can compare any genomes from and for anyone and systematically search for regions which are characterized by the presence or absence of certain sequences - or, to put it simply, what is missing and where in the genome and when it got lost or when it newly emerged. This makes it possible to recognize relationships among species or individuals. The Münster researchers have now published details of their new development - which, like its predecessor - is freely available on the internet - in the journal Genome Research.

Jürgen Schmitz, a biologist and zoologist at the Institute of Experimental Pathology at Münster University's Faculty of Medicine, led the study together with Dr. Gennady Churakov and for him it represents a "unique, forward-pointing opportunity to take a close look at the mutability of multiple genomes". It means that not only genome evolutions can be analysed, but also the occurrence of genetic diseases as a result of deletions or insertions - i.e. the loss of a DNA segment or the insertion of a new one. The decisive difference between the new model and its predecessor, GPAC - which has been used hundreds of thousands of times since it was activated - is that 2-n-way can sequence any number of genomes. "The tool is a response to the modern genomic era - and it is a piece of software which, despite the complexity behind it, can be used by anyone, whether a non-medical layperson, a student or a professor. Last but not least, the tool links up a very wide range of areas, such as evolution, population genetics and medicine" says Schmitz.

The term "2-n-way" is derived from two abbreviations used by specialists: "2-way" stands for the linear alignment of sequences to be compared; and "n-way" means the combination of individual components and the subsequent multiple comparison. But users do not need to know such background information. "They only have to download on the internet the genomes they want to compare. One source, for example, is the website of the National Center for Biotechnology Information (NCBI) in the USA. The genomes fed into 2-n-way are then aligned with each other by the software. The genes which are of particular interest are selected from the genomic "coordinates" - or "loci", to give them their proper technical term. "The search can be geared for example to some or all of the so-called jumping genes, i.e. those genes which have changed their position in the genome," Schmitz explains.

If for example a search is made for certain jumping genes in humans, chimpanzees or rhesus monkeys, the results are given in a table with "plus" and "minus". If the evaluation contains two finds and an exact gap in the rhesus monkey, then the conclusion is that humans and chimpanzees have inherited the jumping gene from a common ancestor and are therefore closely related - while the rhesus monkey still displays the original locus without any insertion and is therefore only distantly related. However, the software not only indicates whether a certain insertion is present, but also the region in which it is to be found. In addition to the table of correlations, 2-n-way also provides the user with a list of DNA sequences for all loci.

Although the new tool has only just been made public, the team of researchers is already looking ahead - working on the simplification of the individual creation of 2-ways, i.e. the alignment. "This is a process which, at the moment, can take up a lot of time - which is a bit annoying," says Schmitz. Otherwise, he comments, the tool "has been tested intensively and is absolutely perfect".

Credit: 
University of Münster

Fine-tuning stem cell metabolism prevents hair loss

image: Cross-section of a skin biopsy showing hair follicles extending downwards from the skin surface. Low oxygen around the hair follicle stem cells activates Rictor signaling (phosphorylated Akt; in magenta) locally at this site. Cell nuclei are labeled in blue.

Image: 
Sara Wickström

A team of researchers from Cologne and Helsinki has discovered a mechanism that prevents hair loss: hair follicle stem cells, essential for hair to regrow, can prolong their life by switching their metabolic state in response to low oxygen concentration in the tissue. The team was led by Associate Professor Sara Wickström (University of Helsinki and Max Planck Institute for the Biology of Ageing) and the dermatologist Professor Sabine Eming (University of Cologne), and included researchers from the University of Cologne's Cluster of Excellence in Aging Research CECAD, the Max Planck Institute for the Biology of Ageing, Collaborative Research Centre 829 'Molecular Mechanisms Regulating Skin Homeostasis', the Center for Molecular Medicine (CMMC) (all in Cologne), and the University of Helsinki. The paper 'Glutamine Metabolism Controls Stem Cell Fate Reversibility and Long-Term Maintenance in the Hair Follicle' has been published in Cell Metabolism.

Every day, tissues such as the skin and its hair follicles are exposed to environmental damage like ultraviolet radiation. Damaged material is continuously removed and renewed. On average, 500 million cells and 100 hairs are shed every day, amounting to 1.5 gram of material. The dead material is replaced by stem cells, which are specialized, highly proliferative and long-lived. Tissue function relies on the activity and health of these stem cells; compromised function or reduced number leads to aging. 'Although the critical role of stem cells in aging is established, little is known about the mechanisms that regulate the long-term maintenance of these important cells. The hair follicle with its well understood functions and clearly identifiable stem cells was a perfect model system to study this important question', said Sara Wickström.

To understand what made stem cells functionally distinct from their differentiated daughter cells, the team investigated the transcriptional and metabolic profiles of the two cell populations. 'Intriguingly, these studies showed that stem cells and daughter cells have distinct metabolic characteristics', said Dr. Christine Kim, co-leading scientist of the study. 'Our analyses further predicted that Rictor, an important but relatively poorly understood molecular component of the metabolic master regulator mTOR pathway, would be involved.' The mTOR signal transduction regulates processes like growth, energy, and oxygen consumption of cells.

In more detailed analyses, the team showed that stem cell depletion was due to the loss of metabolic flexibility. At the end of each regenerative cycle, during which a new hair is made, the stem cells will return to their specific location and resume a quiescent state. Dr. Xiaolei Ding, the other co-leading scientist, explained: 'The key finding of this study is that this so called "fate reversibility" requires a shift from glutamine metabolism and cellular respiration to glycolysis. The stem cells reside in an environment with low oxygen availability and thus use glucose rather than glutamine as a carbon source for energy and protein synthesis. This shift is triggered by the low oxygen concentration and Rictor signaling. The removal of Rictor impaired the ability of this stem cell fate reversal, triggering slow, age-dependent exhaustion of the stem cells and age-induced hair loss.' Ding and Eming had recently generated a genetic mouse model to study Rictor function and observed that mice lacking Rictor had significantly delayed hair follicle regeneration and cycling, which indicated impaired stem cell regulation. 'Interestingly, with aging these mice showed hair loss and reduction in stem cell numbers', said Ding.

'A major future goal will be to understand how these preclinical findings might translate into stem cell biology in humans and potentially could be pharmaceutically harnessed to protect from hair follicle aging', said Eming. 'We are particularly excited about the observation that the application of a glutaminase inhibitor was able to restore stem cell function in the Rictor-deficient mice, proving the principle that modifying metabolic pathways could be a powerful way to boost the regenerative capacity of our tissues.'

Credit: 
University of Cologne

Scientists precisely measure total amount of matter in the universe

image: The team determined that matter makes up about 31% of the total amount of matter and energy in the universe. Cosmologists believe about 20% of the total matter is made of regular -- or "baryonic" matter -- which includes stars, galaxies, atoms, and life, while about 80% is made of dark matter, whose mysterious nature is not yet known but may consist of some as-yet-undiscovered subatomic particle.

Image: 
Mohamed Abdullah, UC Riverside.

RIVERSIDE, Calif. -- A top goal in cosmology is to precisely measure the total amount of matter in the universe, a daunting exercise for even the most mathematically proficient. A team led by scientists at the University of California, Riverside, has now done just that.

Reporting in the Astrophysical Journal, the team determined that matter makes up 31% of the total amount of matter and energy in the universe, with the remainder consisting of dark energy.

"To put that amount of matter in context, if all the matter in the universe were spread out evenly across space, it would correspond to an average mass density equal to only about six hydrogen atoms per cubic meter," said first author Mohamed Abdullah, a graduate student in the UCR Department of Physics and Astronomy. "However, since we know 80% of matter is actually dark matter, in reality, most of this matter consists not of hydrogen atoms but rather of a type of matter which cosmologists don't yet understand."

Abdullah explained that one well-proven technique for determining the total amount of matter in the universe is to compare the observed number and mass of galaxy clusters per unit volume with predictions from numerical simulations. Because present-day galaxy clusters have formed from matter that has collapsed over billions of years under its own gravity, the number of clusters observed at the present time is very sensitive to cosmological conditions and, in particular, the total amount of matter.

"A higher percentage of matter would result in more clusters," Abdullah said. "The 'Goldilocks' challenge for our team was to measure the number of clusters and then determine which answer was 'just right.' But it is difficult to measure the mass of any galaxy cluster accurately because most of the matter is dark so we can't see it with telescopes."

To overcome this difficulty, the UCR-led team of astronomers first developed "GalWeight", a cosmological tool to measure the mass of a galaxy cluster using the orbits of its member galaxies. The researchers then applied their tool to observations from the Sloan Digital Sky Survey (SDSS) to create "GalWCat19," a publicly available catalog of galaxy clusters.  Finally, they compared the number of clusters in their new catalog with simulations to determine the total amount of matter in the universe.

"We have succeeded in making one of the most precise measurements ever made using the galaxy cluster technique," said coauthor Gillian Wilson, a professor of physics and astronomy at UCR in whose lab Abdullah works. "Moreover, this is the first use of the galaxy orbit technique which has obtained a value in agreement with those obtained by teams who used noncluster techniques such as cosmic microwave background anisotropies, baryon acoustic oscillations, Type Ia supernovae, or gravitational lensing."

"A huge advantage of using our GalWeight galaxy orbit technique was that our team was able to determine a mass for each cluster individually rather than rely on more indirect, statistical methods," said the third coauthor Anatoly Klypin, an expert in numerical simulations and cosmology.

By combining their measurement with those from the other teams that used different techniques, the UCR-led team was able to determine a best combined value, concluding that matter makes up 31.5±1.3% of the total amount of matter and energy in the universe.

Credit: 
University of California - Riverside

Unconventional T cell subset enriched in airways of some patients with severe COVID-19

Unconventional T cells called mucosa-associated invariant T (MAIT) cells are recruited to the airways and strongly activated in some patients with severe COVID-19, a new study has found, suggesting the cells' possible involvement in the development of disease. These findings corroborate other recent studies that highlight potential associations between strong MAIT cell activation and severe COVID-19 outcomes. MAIT cells, representing 1% to 10% of T cells in the blood, can readily home into specific tissues and are particularly abundant in the liver and lungs. Emerging evidence has shown these primarily antibacterial cells can also act as quick-acting sensors of viral infection as well, leading Tiphaine Parrot and colleagues to investigate the MAIT cell population in the context of SARS-CoV-2. They analyzed blood samples taken from 24 hospitalized COVID-19 patients with moderate and severe disease, as well as 23 patients recovering from mild disease and 22 in recovery after severe disease. They discovered MAIT cells declined significantly in the blood and swarmed the airways of patients with COVID-19, compared with controls. By contrast, MAIT cell levels normalized in the blood of patients in recovery. Together, these patterns are consistent with the concept that MAIT cells home into tissues during disease and later return into the blood when disease is resolved. Furthermore, gene expression analyses revealed that MAIT cell expression of certain inflammatory proteins in the airways - including IL-17A, CD69, and CXCR3 - was associated with poor clinical outcome. Four out of 24 patients studied here who died at hospital had significantly higher CD69 expression by MAIT cells than patients who survived. The authors note several limitations of their study that must be resolved with further work, including that the cohorts studied here do not reflect the full complexity of COVID-19.

Credit: 
American Association for the Advancement of Science (AAAS)

Spinal injuries: the recovery of motor skills thanks to nanomaterials

video: Virtual journey into 3-dimensional carbon nanotube structures (visualised by confocal microscopy)

Available also at https://youtu.be/SqD9Z26Eacw

Image: 
Raffaele Casani and Pedro Ramos-Cabre

A new study conducted by SISSA and the University of Trieste shows the efficacy of carbon nanotube implants to restore motor functions and paves the way for a new therapeutic approach for spinal cord injuries.

Re-establishing motor skills and neuronal connectivity thanks to the implantation of carbon nanotubes in the injury site. This is the result of a new study conducted by SISSA - Scuola Internazionale Superiore di Studi Avanzati and the University of Trieste that rewards a ten years interdisciplinary collaboration. For the first time, the researchers have used nanomaterial implants in animals with spinal injury, observing the regrowth of nerve fibres and the restoration of motor functions. The research, published in PNAS - Proceedings of the National Academy of Sciences, shows the potential of therapeutic approaches that use the mechanical and electric properties of regenerative scaffolds to treat the injured area.

"We have been studying the interaction between neurons and carbon nanotubes for 15 years. Finally, we have been able to challenge their function in vivo", say Laura Ballerini, neurophysiologist at SISSA, and Maurizio Prato, chemist at the University of Trieste, who have been investigating nerve cell growth when interfaced to smart materials, such as carbon nanotubes in the last decade, using increasingly complex systems. "In recent years, we passed from single neurons to brain tissue explants and from single nanotubes to two-dimensional structures and, now, three dimensional ones."

"We studied the effect of the carbon nanotube implant in small mammals with a disease model of incomplete spinal cord injury," explains Sadaf Usmani, PhD in neurobiology and lead author of the study. "We observed their motor recovery during the next six months through standard protocols for locomotor evaluation which revealed a greater recovery of motor skills when compared to non-implanted animals".

This phenomenon is associated with nerve fibre regrowth through the injury site, as shown by the magnetic resonance experiments carried out in collaboration with the Center for Cooperative Research in Biomaterials (CIC biomaGUNE). A regrowth that is certainly favoured by nanotube implantation, explain Ballerini and Prato. "Nerve fibre regeneration is promoted by the physical characteristics of nanomaterials. These implants are able to guarantee mechanical support and, at the same time, interact electrically with neurons."

"The functionality of the regenerated tissue was not taken for granted, just as the biocompatibility of the implants" continue the researchers "And yet, not only there have been no cases of rejection, but electron microscope observations and the use of specific markers have confirmed that there is no real boundary between the tissue surrounding the injury, the regenerated tissue and the nanomaterials."

These results not only confirm the possible applications of the nanomaterials in the biomedical sector but also pave the way to new therapeutic approaches which use the physical, mechanical and electrical properties in particular, of the injured zone to favour functional recovery.

Credit: 
Scuola Internazionale Superiore di Studi Avanzati

New study finds novel functions of the pyruvate-sensing protein PdhR in E. Coli

image: Pyruvate is a key compound to many essential biological pathways that generate energy (TCA cycle, respiratory electron transfer, fatty acid oxidation) in E. coli. The transcription factor PdhR responds to the amount of intracellular pyruvate present to regulate these pathways.

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Microbial Genomics, Tokyo Tech

Organisms, ranging from bacteria to humans, run on an interconnected series of metabolic pathways--with glycolysis being the essential process that generates energy from sugars (glucose) in food. Pyruvate is the final product of glycolysis: it is an important molecule that acts as a node between different pathways (Figure 1). To better understand how these pathways work, a team of scientists, led by Dr Tomohiro Shimada from Meiji University and including Dr Akira Ishihama from Hosei University and Dr Sousuke Imamura from Tokyo Institute of Technology (Tokyo Tech), decided to investigate a protein called "PdhR," the master regulator of pyruvate catabolism (or breakdown) in Escherichia coli (a common model organism). They knew from previous research that PdhR regulates the expression of at least nine proteins involved in carbon metabolism pathways (breakdown of sugars into energy sources). But, given the many roles of pyruvate from scavenging free radicals to generating amino acids, it was logical to think PdhR had multiple targets.

Researchers used a process called gSELEX (Genomic SELEX) screening, in which PdhR is mixed with small pieces of E. coli genome. PdhR was tagged with a marker that allowed researchers to isolate the targets of PdhR. This led to the successful identification of multiple targets of PdhR. "We were able to find 16-27 possible targets of PdhR this way," Dr Shimada explained. "And from these, we decided to analyze the ones that had never been identified before. The goal was to find new pathways involving PdhR."

The team identified PdhR regulatory targets that were involved in bacterial movement, specifically acting as a repressor of genes affecting flagella (the appendage that many bacteria use to move). They also found that PdhR regulated breakdown of fatty acids (an important energy source in bacteria) by suppressing a protein that inhibits this process. In other words, active PdhR decreases bacterial mobility and increases fatty acid degradation--functions of PdhR that are completely novel. Moreover, the scientists also identified other carbon-metabolism genes regulated by PdhR, including enzymes that produces pyruvate during glycolysis, lactate metabolism, and TCA cycle.

The scientists are optimistic that these findings from E. coli can be applied to more complex, multicellular animals. They could also help us to better manipulate E. coli metabolism, which has important implications for bioengineering and molecular biology experiments." Dr Shimada concludes, "Our work allowed us to expand the role of PdhR beyond what was already known. Because pyruvate concentrations influence PdhR activity, these results really helps us better understand the critical central role of pyruvate in E. coli metabolism. E. coli is an extremely common bacteria, and understanding it can lead to significant insights into the medical field."

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Tokyo Institute of Technology

Boosting public trust in scientists hangs on communications methods

image: Geah Pressgrove, WVU associate professor and program chair of advertising and public relations

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West Virginia University

While debate over COVID-19 guidelines and vaccine development has raised skeptics' eyebrows and undermined confidence, a West Virginia University associate professor says that communication is essential for the science community to gain the American public's trust. According to Geah Pressgrove, scientists and communications professionals need to rethink how they communicate through four distinct dimensions of trust: competence, integrity, benevolence and openness.

Quotes

"In practice, communication objectives should be considered when assessing trust. In other words, 'What are you trying to accomplish with the communication to your audience?' Those objectives should influence the ways in which you assess perceptions. For instance, we see many science communicators simply assessing the outcome of knowledge gain; however, there is substantial evidence that knowledge doesn't change behaviors."

"We set out to increase conceptual clarity of trust and found that a four-factor measurement scale provides value when measuring perceptions of scientists, depending on the communication objectives and research goals. In this solution, items measure competence (ability/expertise), integrity (honesty), benevolence (warmth) and openness (willingness to listen)."

"It is reasonable to assume the public is skeptical of science-related issues. In the past, there has been a tendency towards dumping volumes of information and expecting our audience to naturally understand and accept the claims. Instead, we need to refocus on the communication objectives that make the most sense for science-based communication. Recognizing when and why people trust scientists will help us communicate more effectively by putting the emphasis where needed." - Geah Pressgrove, associate professor, advertising and public relations program chair, WVU Reed College of Media

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West Virginia University

New potential treatment approach for patients with salt sensitive hypertension

(Boston)--High blood pressure (hypertension) affects one in two U.S. adults and can cause hardening and thickening of the arteries (atherosclerosis), which can lead to heart attacks, strokes or other complications including chronic kidney disease. Dietary salt intake can evoke salt-sensitive hypertension, which exists in approximately half of hypertensive patients.

A new study from Boston University School of Medicine (BUSM) has found that an alpha adrenoceptor blocker (a class of drugs that relaxes smooth muscle or blood vessels) may represent a new treatment approach for patients with salt sensitive hypertension. This is the first study to demonstrate that α1-adrenoceptor antagonism reduces the activity of a mechanism in the kidney that reabsorbs salt to reduce blood pressure.

The researchers used an experimental model that was fed a high salt diet (to model the content of a western diet) which led to an increase in their blood pressure. A portion of these models were then treated with an alpha 1 adrenoceptor blocker that reduced their blood pressure by decreasing the activity of a pathway in the kidney that reabsorbs salt. "Our data suggest blocking renal α1-adrenoceptors may represent a new treatment approach for patients with salt sensitive hypertension," said corresponding author Richard Wainford, PhD, associate professor of Pharmacology & Experimental Therapeutics at BUSM.

According to the researcher this study highlights the critical role of looking at the disease of hypertension in an integrated way by examining the interaction between multiple organ systems, in this case the sympathetic nervous system and kidney versus working in isolation. "We hope that these studies, that highlight a new mechanism underlying the salt sensitivity of blood pressure, will drive new treatment approaches for hypertension."

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Boston University School of Medicine

SwRI study describes discovery of close binary trans-Neptunian object

image: This image is an artist's impression of the trans-Neptunian object that two Southwest Research Institute scientists recently discovered is a binary object.

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Southwest Research Institute

SAN ANTONIO -- Sept. 28, 2020 -- A new study authored by Southwest Research In-stitute scientists Rodrigo Leiva and Marc Buie reveals the binary nature of a trans-Neptunian object (TNO). Leiva and Buie utilized data obtained by the Research and Education Collaborative Occultation Network (RECON), a citizen science research net-work dedicated to observing the outer solar system. The study was published this month in The Astrophysical Journal.

Trans-Neptunian objects (TNOs) are small icy bodies that orbit the Sun beyond Nep-tune. Binary TNOs occur when two of these objects orbit each other while together or-biting the Sun. Leiva and Buie discovered two objects in a particularly close gravita-tional configuration. The pair was detected using a stellar occultation, which occurs when an object passes between Earth and a distant star which hides, or "occults," the star from view. Observers located in the path of the object's shadow can record the star blinking out and reappearing. The length of time that the object blocks the starlight can be used to determine its size.

"In this instance, the occulted star also turned out to be a binary system. Binary stars are not unusual and binary objects are not unusual," Buie said. "But it is unusual that we had a binary TNO occulting a binary star."

"What's also interesting and unusual is this object's characteristics," Leiva said. "The two components are quite close, only 350 kilometers apart. Most binary TNOs are very separated, usually 1,000 kilometers or more. This closeness makes this type of binary TNO difficult to detect with other methods, which is what RECON was designed to ac-complish."

The discovery of the new TNO was made possible by RECON, a collection of 56 obser-vation stations stretching from Yuma, Arizona, to Orville, Washington. The NSF-funded project provides each station with an array of observation equipment, including 11-inch telescopes. High school teachers are trained by Leiva, Buie and Fiske Planetari-um Director Dr. John Keller to operate the stations and observe occultations so they can then teach students how to make the same observations. RECON has seen several stu-dents go on to do research related to their observations in college.

"To me this project is citizen science at its best," Buie said. "They're learning as well as making observations and helping to collect data. If they didn't do this, we wouldn't learn about these objects."

RECON stations are commonly placed in small communities along an ideal line, from the southern to the northern border of the United States, for observation of stellar occul-tations. Eight additional stations were established in Canada in 2018 by colleagues of Leiva and Buie.

Going forward, Leiva and Buie will continue to search for previously unobserved TNOs, with the aim of discovering whether close binaries are common or unusual in our Solar System.

"Most models of the Solar System indicate that binaries are very common, particularly close binaries like this one," Leiva said. "If you have an accurate measurement of how common they are, you can fine tune these models."

"Our overarching aim is to know how common close binary TNOs are," Buie said. "Is this object one in a million or just like 90% of them? This is fueling our knowledge for building better models of how the Solar System formed."

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Southwest Research Institute