bluuebunny/crossref_metadata_2025_split huggingface dataset:
Membrane-mediated forces can stabilize tubular assemblies of I-Bar proteins
Authors: Jarin Z. , Pak A. J. , Bassereau P. , Voth G. A. 
Published: June 2020

AbstractCollective action by Inverse-BAR (I-BAR) domains drive micron-scale membrane remodeling. The macroscopic curvature sensing and generation behavior of I-BAR domains is well characterized, and computational models have suggested various mechanisms on simplified membrane systems, but there remain missing connections between the complex environment of the cell and the models proposed thus far. Here, we show a connection between the role of protein curvature and lipid clustering in the stabilization of large membrane deformations. We find lipid clustering provides a directional membrane-mediated interaction between membrane-bound I-BAR domains. Lipid clusters stabilize I-BAR domain aggregates that would not arise through membrane fluctuation-based or curvature-based interactions. Inside of membrane protrusions, lipid cluster-mediated interaction draws long side-by-side aggregates together resulting in more cylindrical protrusions as opposed to bulbous, irregularly shaped protrusions.Statement of SignificanceMembrane remodeling occurs throughout the cell and is crucial to proper cellular function. In the cellular environment, I-BAR proteins are responsible for sensing membrane curvature and initiating the formation of protrusions outward from the cell. Additionally, there is a large body of evidence that I-BAR domains are sufficient to reshape the membrane on scales much larger than any single domain. The mechanism by which I-BAR domains can remodel the membrane is uncertain. However, experiments show that membrane composition and most notably negatively-charge lipids like PIP2play a role in the onset of tubulation. Using coarse-grained models, we show that I-BAR domains can cluster negatively charge lipids and clustered PIP2-like membrane structures facilitate a directional membrane-mediated interaction between I-BAR domains.
Worldwide strains of the nematophagous fungusPochonia chlamydosporiaare endophytic in banana roots and promote plant growth
Authors: Mingot-Ureta Cristina , Lopez-Moya Federico , Lopez-Llorca Luis Vicente 
Published: June 2020

SUMMARYThe biocontrol fungus,Pochonia chlamydosporia, colonizes endophytically banana roots. Root hairs and root surface were found colonize by the fungus using a stable GFP transformant. Hyphal penetration of root cells was also observed. Spores ofP. chlamydosporia123, significantly increase root and leaf length and weight in banana plantlets(Musa acuminatacv. ‘Dwarf Cavendish’) in growth chamber experiments 30 days post-inoculation (dpi). In greenhouse 8L pot experiments,P. chlamydosporia123 spore inoculation significantly increases leaf and root length and leaf weight in banana plants (75 dpi). Spore inoculation ofP. chlamydosporiastrains from worldwide origin (Pc21 Italy, Pc123 Spain, Pc399 China, and Pccat Cuba), significantly increases root, corm and leaf length and weight in banana plantlets. Pc21 was the best colonizer of banana roots. Consequently, this strain significantly increases most banana root and leaf length. Root colonization byP. chlamydosporiawas also detected using cultural techniques and qPCR.
On phage adsorption to bacterial chains
Authors: Eriksen R. S. , Mitarai N. , Sneppen K. 
Published: June 2020

ABSTRACTBacteria often arrange themselves in various spatial configurations which changes how they interact with their surroundings. In this paper, we investigatein silicohow the structure of the bacterial arrangements influences the adsorption of bacteriophages. We quantify how the adsorption rate scales with the number of bacteria in the arrangement, and show that the adsorption rates for microcolonies (increasing with exponent ∼1/3) and bacterial chains (increasing with exponent ∼0.5 − 0.8) are substantially lower than for well-mixed bacteria (increasing with exponent 1). We further show that, after infection, the spatially clustered arrangements reduce the effective burst size by more than 50 % and cause substantial superinfections in a very short time interval after phage lysis.SIGNIFICANCEWhen bacteria forms clusters they substantially change their exposure to invading phages and other external agents from the well-mixed scenario. Despite this fact, much research has focused on and is focusing on using well-mixed bacteria. Understanding the kinetics of the spatial structures is paramount to developing robust analyses and theories of experimental results. We carefully investigate how the clusters lower the adsorption rate of external phages and how the clustering modifies the hit probabilities for the bacteria.
Investigation of the effect of temperature on the structure of SARS-Cov-2 Spike Protein by Molecular Dynamics Simulations
Authors: Rath Soumya Lipsa , Kumar Kishant 
Published: June 2020

ABSTRACTStatistical and epidemiological data imply temperature sensitivity of the SARS-CoV-2 coronavirus. However, the molecular level understanding of the virus structure at different temperature is still not clear. Spike protein is the outermost structural protein of the SARS-CoV-2 virus which interacts with the Angiotensin Converting Enzyme 2 (ACE2), a human receptor, and enters the respiratory system. In this study, we performed an all atom molecular dynamics simulation to study the effect of temperature on the structure of the Spike protein. After 200ns of simulation at different temperatures, we came across some interesting phenomena exhibited by the protein. We found that the solvent exposed domain of Spike protein, namely S1, is more mobile than the transmembrane domain, S2. Structural studies implied the presence of several charged residues on the surface of N-terminal Domain of S1 which are optimally oriented at 10-30 °C. Bioinformatics analyses indicated that it is capable of binding to other human receptors and should not be disregarded. Additionally, we found that receptor binding motif (RBM), present on the receptor binding domain (RBD) of S1, begins to close around temperature of 40 °C and attains a completely closed conformation at 50 °C. The closed conformation disables its ability to bind to ACE2, due to the burying of its receptor binding residues. Our results clearly show that there are active and inactive states of the protein at different temperatures. This would not only prove beneficial for understanding the fundamental nature of the virus, but would be also useful in the development of vaccines and therapeutics.Graphical AbstractHighlightsStatistical and epidemiological evidence show that external climatic conditions influence the SARS-CoV infectivity, but we still lack a molecular level understanding of the same.Here, we study the influence of temperature on the structure of the Spike glycoprotein, the outermost structural protein, of the virus which binds to the human receptor ACE2.Results show that the Spike’s S1 domain is very sensitive to external atmospheric conditions compared to the S2 transmembrane domain.The N-terminal domain comprises of several solvent exposed charged residues that are capable of binding to human proteins. The region is specifically stable at temperatures ranging around 10-30° C.The Receptor Binding Motif adopts a closed conformation at 40°C and completely closes at higher temperatures making it unsuitable of binding to human receptors
α-Synuclein facilitates dopamine release during burst firing of substantia nigra neuronsin vivo
Authors: Somayaji Mahalakshmi , Cataldi Stefano , Edwards Robert H. , Mosharov Eugene V. , Sulzer David 
Published: June 2020

Abstractα-Synuclein is expressed at high levels at presynaptic terminals, but defining its role on neurotransmission under physiologically-relevant conditions has proven elusive. We report that α-synuclein is responsible for a rapid facilitation of dopamine release during action potential burstsin vivo. This occurs in tandem with a far slower stimulus-dependent depression, appears to be independent of the presence of β- and γ-synucleins or effects on presynaptic calcium and is consistent with a role for synucleins in the enhancement of synaptic vesicle fusion and turnover. The results indicate that the presynaptic effects of α-synuclein are dependent on specific patterns of neuronal activity.
The long-distance flight behavior ofDrosophilasuggests a general model for wind-assisted dispersal in insects
Authors: Leitch Katherine , Ponce Francesca , van Breugel Floris , Dickinson Michael H. 
Published: June 2020

AbstractDespite the ecological importance of long-distance dispersal in insects, its underlying mechanistic basis is poorly understood. One critical question is how insects interact with the wind to increase their travel distance as they disperse. To gain insight into dispersal using a species amenable to further investigation using genetic tools, we conducted release-and-recapture experiments in the Mojave Desert using the fruit fly,Drosophila melanogaster. We deployed chemically-baited traps in a 1 km-radius ring around the release site, equipped with machine vision systems that captured the arrival times of flies as they landed. In each experiment, we released between 30,000 and 200,000 flies. By repeating the experiments under a variety of conditions, we were able to quantify the influence of wind on flies’ dispersal behavior. Our results confirm that even tiny fruit flies could disperse ∼15 km in a single flight in still air, and might travel many times that distance in a moderate wind. The dispersal behavior of the flies is well explained by a model in which animals maintain a fixed body orientation relative to celestial cues, actively regulate groundspeed along their body axis, and allow the wind to advect them sideways. The model accounts for the observation that flies actively fan out in all directions in still air, but are increasingly advected downwind as winds intensify. In contrast, our field data do not support a Lévy flight model of dispersal, despite the fact that our experimental conditions almost perfectly match the core assumptions of that theory.Significance StatementFlying insects play a vital role in terrestrial ecosystems, and their decline over the past few decades has been implicated in a collapse of many species that depend upon them for food. By dispersing over large distances, insects transport biomass from one region to another and thus their flight behavior influences ecology on a global scale. Our experiments provide key insight into the dispersal behavior of insects, and suggest that these animals employ a single algorithm that is functionally robust in both still air and under windy conditions. Our results will make it easier to study the ecologically important phenomenon of long-distance dispersal in a genetic model organism, facilitating the identification of cellular and genetic mechanisms.
COVID-19 Variants Database: A repository for Human SARS-CoV-2 Polymorphism Data
Authors: Rakha Allah , Rasheed Haroon , Batool Zunaira , Akram Javed , Adnan Atif , Du Jiang 
Published: June 2020

ABSTRACTCOVID-19 is a newly communicable disease with a catastrophe outbreak that affects all over the world. We retrieved about 8,781 nucleotide fragments and complete genomes of SARS-CoV-2 reported from sixty-four countries. The CoV-2 reference genome was obtained from the National Genomics Data Center (NGDC), GISAID, and NCBI Genbank. All the sequences were aligned against reference genomes using Clustal Omega and variants were called using in-house built Python script. We intend to establish a user-friendly online resource to visualize the variants in the viral genome along with the Primer Infopedia. After analyzing and filtering the data globally, it was made available to the public. The detail of data available to the public includes mutations from 5688 SARS-CoV-2 sequences curated from 91 regions. This database incorporated 39920 mutations over 3990 unique positions. According to the translational impact, these mutations include 11829 synonymous mutations including 681 synonymous frameshifts and 21701 nonsynonymous mutations including 10 nonsynonymous frameshifts. Development of SARS-CoV-2 mutation genome browsers is a fundamental step obliging towards the virus surveillance, viral detection, and development of vaccine and therapeutic drugs. The SARS-COV-2 mutation browser is available athttp://covid-19.dnageography.com.
The architecture of co-morbidity networks of physical and mental health conditions in military veterans
Authors: Alexander-Bloch Aaron F , Raznahan Armin , Shinohara Russell T , Mathias Samuel R , Bathulapalli Harini , Bhalla Ish P , Goulet Joseph , Satterthwaite Theodore , Bassett Danielle S. , Glahn David C , Brandt Cynthia A. 
Published: June 2020

AbstractCo-morbidity between medical and psychiatric conditions is commonly considered between individual pairs of conditions. However, an important alternative is to consider all conditions as part of a co-morbidity network, which encompasses all interactions between patients and a healthcare system. Analysis of co-morbidity networks could detect and quantify general tendencies not observed by smaller-scale studies. Here, we investigate the co-morbidity network derived from longitudinal healthcare records from approximately 1-million U.S. military veterans, a population disproportionately impacted by psychiatric morbidity and psychological trauma. Network analyses revealed marked and heterogenous patterns of co-morbidity, including a multi-scale community structure composed of groups of commonly co-morbid conditions. Psychiatric conditions including posttraumatic stress disorder were strong predictors of future medical morbidity. Neurological conditions and conditions associated with chronic pain were particularly highly co-morbid with psychiatric conditions. Across conditions, the degree of co-morbidity was positively associated with mortality. Co-morbidity was modified by biological sex and could be used to predict future diagnostic status, with out-of-sample prediction accuracy of 90-92%. Understanding complex patterns of disease co-morbidity has the potential to lead to improved designs of systems of care and the development of targeted interventions that consider the broader context of mental and physical health.
Identifying novel factors associated with COVID-19 transmission and fatality using the machine learning approach
Authors: Li Mengyuan , Zhang Zhilan , Cao Wenxiu , Liu Yijing , Du Beibei , Chen Canping , Liu Qian , Uddin Md. Nazim , Jiang Shanmei , Chen Cai , Zhang Yue , Wang Xiaosheng 
Published: June 2020

AbstractThe COVID-19 virus has infected millions of people and resulted in hundreds of thousands of deaths worldwide. By using the logistic regression model, we identified novel critical factors associated with COVID19 cases, death, and case fatality rates in 154 countries and in the 50 U.S. states. Among numerous factors associated with COVID-19 risk, we found that the unitary state system was counter-intuitively positively associated with increased COVID-19 cases and deaths. Blood type B was a protective factor for COVID-19 risk, while blood type A was a risk factor. The prevalence of HIV, influenza and pneumonia, and chronic lower respiratory diseases was associated with reduced COVID-19 risk. Obesity and the condition of unimproved water sources were associated with increased COVID-19 risk. Other factors included temperature, humidity, social distancing, smoking, and vitamin D intake. Our comprehensive identification of the factors affecting COVID-19 transmission and fatality may provide new insights into the COVID-19 pandemic and advise effective strategies for preventing and migrating COVID-19 spread.
On the interplay between mobility and hospitalization capacity during the COVID-19 pandemic: The SEIRHUD model
Authors: Veloz Tomás , Maldonado Pedro , Ropert Samuel , Ravello César , Mora Soraya , Barrios Alejandra , Villaseca Tomás , Valdenegro César , Perez-Acle Tomás 
Published: June 2020

AbstractMeasures to reduce the impact of the COVID-19 pandemic require a mix of logistic, political and social capacity. Depending on the country, different approaches to increase hospitalization capacity or to properly apply lock-downs are observed. In order to better understand the impact of these measures we have developed a compartmental model which, on the one hand allows to calibrate the reduction of movement of people within and among different areas, and on the other hand it incorporates a hospitalization dynamics that differentiates the available kinds of treatment that infected people can receive. By bounding the hospitalization capacity, we are able to study in detail the interplay between mobility and hospitalization capacity.
The interplay between information flux and temporal dynamics in infraslow frequencies
Authors: Golesorkhi Mehrshad , Tumati Shankar , Gomez-Pilar Javier , Stamatakis Emmanuel. A. , Northoff Georg. 
Published: June 2020

AbstractUnlike the brain’s faster frequencies, the exact role of its more powerful infraslow frequencies (ISF, 0.01 – 0.1Hz) in information processing remains poorly understood. Do and how ISF process information? We investigate information processing and related temporal dynamics of ISF in resting and task state fMRI. To quantify information, we apply the Lempel-Ziv complexity (LZC), a measure of signal compression indexing information. The LZC is combined with direct measurement of the dynamics of ISF themselves, namely their power spectral density by median frequency (MF). We demonstrate the following: (I) topographical differences in resting state between higher- and lower-order networks, showing statistically lower LZC in the former; (II) task-related changes in LZC; (III) modulation of LZC associated with MF changes, with low and high MF resting-state values correlated with different degrees of LZC change. In sum, we provide evidence that ISF carry and process information as mediated through their temporal dynamics.
Phase-separation of EML4-ALK variant 3 is dependent upon an active ALK conformation
Authors: Sampson Josephina , Richards Mark W. , Choi Jene , Fry Andrew M. , Bayliss Richard 
Published: June 2020

ABSTRACTOncogenic fusions involving tyrosine kinases are common drivers of non-small cell lung cancer (NSCLC). There are at least 15 different variants of the EML4-ALK fusion, all of which have a similar portion of ALK that includes the kinase domain, but different portions of EML4. Targeted treatment with ALK tyrosine kinase inhibitors (TKIs) has proven effective but patient outcomes are variable. Here, we focus on one common variant, EML4-ALK V3, which drives an aggressive form of the disease. EML4-ALK V3 protein forms cytoplasmic liquid droplets that contain the signalling proteins GRB2 and SOS1. The TKIs ceritinib and lorlatinib dissolve these droplets and the EML4-ALK V3 protein re-localises to microtubules, an effect recapitulated by an inactivating mutation in the ALK catalytic site. Mutations that promote a constitutively active ALK stabilise the liquid droplets even in the presence of TKIs, indicating that droplets do not depend on kinase activityper se. Uniquely, the TKI alectinib promotes droplet formation of both the wild-type and catalytically inactive EML4-ALK V3 mutant, but not in a mutant that disrupts a hallmark of the kinase activity, the Lys-Glu salt-bridge. We propose that EML4-ALK V3 liquid droplet formation occurs through transient dimerization of the ALK kinase domain in its active conformation in the context of stable EML4-ALK trimers. Our results provide insights into the relationship between ALK activity, conformational state and the sub-cellular localisation of EML4-ALK V3 protein, and reveal the different effects of structurally divergent ALK TKIs on these properties.
An integrative study of five biological clocks in somatic and mental health
Authors: Jansen Rick , Verhoeven Josine , Han Laura KM , Aberg Karolina A , van den Oord Edwin CGJ , Milaneschi Yuri , Penninx Brenda WJH 
Published: June 2020

ABSTRACTBiological clocks have been developed at different molecular levels and were found to be more advanced in the presence of somatic illnesses and mental disorders. However, it is unclear whether different biological clocks reflect similar aging processes and determinants. In ~3000 subjects, we examined whether 5 biological clocks (telomere length, epigenetic, transcriptomic, proteomic and metabolomic clocks) were interrelated and associated to somatic and mental health determinants. Correlations between biological clocks were small (allr<0.2), indicating little overlap. The most consistent associations with the advanced biological clocks were found for male sex, higher BMI, metabolic syndrome, smoking and depression. As compared to the individual clocks, a composite index of all five clocks showed most pronounced associations with health determinants. The large effect sizes of the composite index and the low correlation between biological clocks, indicate that one’s biological age is best reflected by combining aging measures from multiple cellular levels.
2-amino-1,3-benzothiazole-6-carboxamide Preferentially Binds the Tandem Mismatch Motif r(UY:GA)
Authors: Chang Andrew T. , Chen Lu , Song Luo , Zhang Shuxing , Nikonowicz Edward P. 
Published: June 2020

AbstractRNA helices are often punctuated with non-Watson-Crick features that can be the target of chemical compounds, but progress towards identifying small molecules specific for non-canonical elements has been slow. We have used a tandem UU:GA mismatch motif (5’-UG-3’:5’-AU-3’) embedded within the helix of an RNA hairpin as a model to identify compounds that bind the motif specifically. The three-dimensional structure of the RNA hairpin and its interaction with a small molecule compound identified through a virtual screen are presented. The G-A of the mismatch forms a sheared pair upon which the U-U base pair stacks. The hydrogen bond configuration of the U-U pair involves the O2 of the U adjacent to the G and the O4 of the U adjacent to the A. The G-A and U-U pairs are flanked by A-U and G-C base pairs, respectively, and the mismatch exhibits greater stability than when the motif is within the context of other flanking base pairs or when the 5’-3’ orientation of the G-A and U-U is swapped. Residual dipolar coupling constants were used to generate an ensemble of structures against which a virtual screen of 64,480 small molecules was performed to identify candidate compounds that the motif specifically binds. The tandem mismatch was found to be specific for one compound, 2-amino-1,3-benzothiazole-6-carboxamide, which binds with moderate affinity but extends the motif to include the flanking A-U and G-C base pairs. The finding that affinity for the UU:GA mismatch is flanking sequence dependent emphasizes the importance of motif context and potentially increases the number of small non-canonical features within RNA that can be specifically targeted by small molecules.