bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissociation of salts in water under pressure
Authors: Zhang Cunzhi , Giberti Federico , Sevgen Emre , de Pablo Juan J. , Gygi Francois , Galli Giulia 
Published: June 2020

AbstractThe investigation of salts in water at extreme conditions is crucial to understanding the properties of aqueous fluids in the Earth. We report first principles (FP) and classical molecular dynamics simulations of NaCl in the dilute limit, at temperatures and pressures relevant to the Earth’s upper mantle. Similar to ambient conditions, we observe two metastable states of the salt: the contact (CIP) and the solvent-shared ion-pair (SIP), which are entropically and enthalpically favored, respectively. We find that the free energy barrier between the CIP and SIP minima increases at extreme conditions, and that the stability of the CIP is enhanced in FP simulations, consistent with the decrease of the dielectric constant of water. The minimum free energy path between the CIP and SIP becomes smoother at high pressure, and the relative stability of the two configurations is affected by water self-dissociation, which can only be described properly by FP simulations.
Motion corrected MRI differentiates male and female human brain growth trajectories from mid-gestation
Authors: Studholme Colin , Kroenke Christopher D. , Dighe Manjiri 
Published: June 2020

AbstractIt is of considerable scientific, medical, and societal interest to understand the developmental origins of differences between male and female brains. Here we report the use of advances in MR imaging and analysis to accurately measure global, lobe and millimetre scale growth trajectory patterns over 18 gestational weeks in normal pregnancies with repeated measures. Statistical modelling of absolute growth trajectories revealed underlying differences in many measures, potentially reflecting overall body size differences. However, models of relative growth accounting for global measures revealed a complex temporal form, with strikingly similar cortical development in males and females at lobe scales. In contrast, local cortical growth patterns and larger scale white matter volume and surface measures differed significantly between male and female. Many proportional differences were maintained during neurogenesis and over 18 weeks of growth. These indicate sex related sculpting of neuroanatomy begins early in development, before cortical folding, potentially influencing postnatal development.
Intragenic recruitment of NF-κB drives splicing modifications upon activation by the oncogene Tax of HTLV-1
Authors: Ameur Lamya Ben , Marie Paul , Thenoz Morgan , Giraud Guillaume , Combe Emmanuel , Claude Jean-Baptiste , Lemaire Sebastien , Fontrodona Nicolas , Polveche Hélène , Bastien Marine , Gessain Antoine , Wattel Eric , Bourgeois Cyril F. , Auboeuf Didier , Mortreux Franck 
Published: June 2020

AbstractChronic NF-κB activation in inflammation and cancer has long been linked to persistent activation of NF-κB–responsive gene promoters. However, NF-κB factors also massively bind to gene bodies. Here, we demonstrate that recruitment of the NF-κB factor RELA to intragenic regions regulates alternative splicing upon NF-κB activation by the viral oncogene Tax of HTLV-1. Integrative analyses of RNA splicing and chromatin occupancy, combined with chromatin tethering assays, demonstrate that DNA-bound RELA interacts with and recruits the splicing regulator DDX17, in an NF-κB activation-dependent manner. This leads to alternative splicing of target exons due to the RNA helicase activity of DDX17. Similar results were obtained upon Tax-independent NF-κB activation, indicating that Tax likely exacerbates a physiological process where RELA provides splice target specificity. Collectively, our results demonstrate a physical and direct involvement of NF-κB in alternative splicing regulation, which significantly revisits our knowledge of HTLV-1 pathogenesis and other NF-κB-related diseases.
Mesenchymal stem cells offer a drug-tolerant and immune-privileged niche to Mycobacterium tuberculosis
Authors: Jain Neharika , Kalam Haroon , Singh Lakshyaveer , Sharma Vartika , Kedia Saurabh , Das Prasenjit , Ahuja Vineet , Kumar Dhiraj 
Published: June 2020

AbstractAnti-tuberculosis (TB) drugs, while being highly potent in vitro, require prolonged treatment to control Mycobacterium tuberculosis (Mtb) infections in vivo. We report here that mesenchymal stem cells (MSCs) shelter Mtb to help tolerate anti-TB drugs. MSCs readily take up Mtb and allow unabated mycobacterial growth despite having a functional innate pathway of phagosome maturation. Unlike macrophage-resident ones, MSC-resident Mtb tolerates anti-TB drugs remarkably well, a phenomenon requiring proteins ABCC1, ABCG2 and vacuolar-type H+ATPases. Additionally, the classic pro-inflammatory cytokines IFNγ and TNFα aid mycobacterial growth within MSCs. Mechanistically, evading drugs and inflammatory cytokines by MSC-resident Mtb is dependent on elevated PGE2 signaling, which we verify in vivo analyzing sorted CD45−Sca1+CD73+-MSCs from lungs of infected mice. Moreover, MSCs are observed in and around human tuberculosis granulomas, harboring Mtb bacilli. We therefore propose, targeting the unique immune-privileged niche, provided by MSCs to Mtb, can have a major impact on tuberculosis prevention and cure.
High-throughput interrogation of programmed ribosomal frameshifting in human cells
Authors: Mikl Martin , Pilpel Yitzhak , Segal Eran 
Published: June 2020

AbstractProgrammed ribosomal frameshifting (PRF) is the controlled slippage of the translating ribosome to an alternative frame. This process is widely employed by human viruses such as HIV and SARS coronavirus and is critical for their replication. Here, we developed a high-throughput approach to assess the frameshifting potential of a sequence. We designed and tested >12,000 sequences based on 15 viral and human PRF events, allowing us to systematically dissect the rules governing ribosomal frameshifting and discover novel regulatory inputs based on amino acid properties and tRNA availability. We assessed the natural variation in HIV gag-pol frameshifting rates by testing >500 clinical isolates and identified subtype-specific differences and associations between viral load in patients and the optimality of PRF rates. We devised computational models that accurately predict frameshifting potential and frameshifting rates, including subtle differences between HIV isolates. This approach can contribute to the development of antiviral agents targeting PRF.
Integrated analysis of a compendium of RNA-Seq datasets for splicing factors
Authors: Yu Peng , Li Jin , Deng Su-Ping , Zhang Feiran , Grozdanov Petar N. , Chin Eunice W. M. , Martin Sheree D. , Vergnes Laurent , Islam M. Saharul , Sun Deqiang , LaSalle Janine M. , McGee Sean L. , Goh Eyleen , MacDonald Clinton C. , Jin Peng 
Published: June 2020

AbstractA vast amount of public RNA-sequencing datasets have been generated and used widely to study transcriptome mechanisms. These data offer precious opportunity for advancing biological research in transcriptome studies such as alternative splicing. We report the first large-scale integrated analysis of RNA-Seq data of splicing factors for systematically identifying key factors in diseases and biological processes. We analyzed 1,321 RNA-Seq libraries of various mouse tissues and cell lines, comprising more than 6.6 TB sequences from 75 independent studies that experimentally manipulated 56 splicing factors. Using these data, RNA splicing signatures and gene expression signatures were computed, and signature comparison analysis identified a list of key splicing factors in Rett syndrome and cold-induced thermogenesis. We show that cold-induced RNA-binding proteins rescue the neurite outgrowth defects in Rett syndrome using neuronal morphology analysis, and we also reveal that SRSF1 and PTBP1 are required for energy expenditure in adipocytes using metabolic flux analysis. Our study provides an integrated analysis for identifying key factors in diseases and biological processes and highlights the importance of public data resources for identifying hypotheses for experimental testing.
Electric field assisted alignment of monoatomic carbon chains
Authors: Kutrovskaya Stella , Chestnov Igor , Osipov Anton , Samyshkin Vlad , Sapegina Irina , Kavokin Alexey , Kucherik Alexey 
Published: June 2020

AbstractWe stabilize monoatomic carbon chains in water by attaching them to gold nanoparticles (NPs) by means of the laser ablation process. Resulting nanoobjects represent pairs of NPs connected by multiple straight carbon chains of several nanometer lengths. If NPs at the opposite ends of a chain differ in size, the structure acquires a dipole moment due to the difference in work functions of the two NPs. We take advantage of the dipole polarisation of carbon chains for ordering them by the external electric field. We deposit them on a glass substrate by the sputtering method in the presence of static electric fields of magnitudes up to 105 V/m. The formation of one-dimensional carbyne quasi-crystals deposited on a substrate is evidenced by high-resolution TEM and X-ray diffraction measurements. The original kinetic model describing the dynamics of ballistically flowing nano-dipoles reproduces the experimental diagram of orientation of the deposited chains.
Dual-Seq reveals genome and transcriptome of Caedibacter taeniospiralis, obligate endosymbiont of Paramecium
Authors: Pirritano Marcello , Zaburannyi Nestor , Grosser Katrin , Gasparoni Gilles , Müller Rolf , Simon Martin , Schrallhammer Martina 
Published: June 2020

AbstractInterest in host-symbiont interactions is continuously increasing, not only due to the growing recognition of the importance of microbiomes. Starting with the detection and description of novel symbionts, attention moves to the molecular consequences and innovations of symbioses. However, molecular analysis requires genomic data which is difficult to obtain from obligate intracellular and uncultivated bacteria. We report the identification of the Caedibacter genome, an obligate symbiont of the ciliate Paramecium. The infection does not only confer the host with the ability to kill other cells but also renders them immune against this effect. We obtained the C. taeniospiralis genome and transcriptome by dual-Seq of DNA and RNA from infected paramecia. Comparison of codon usage and expression level indicates that genes necessary for a specific trait of this symbiosis, i.e. the delivery of an unknown toxin, result from horizontal gene transfer hinting to the relevance of DNA transfer for acquiring new characters. Prediction of secreted proteins of Caedibacter as major agents of contact with the host implies, next to several toxin candidates, a rather uncharacterized secretome which appears to be highly adapted to this symbiosis. Our data provides new insights into the molecular establishment and evolution of this obligate symbiosis and for the pathway characterization of toxicity and immunity.
Ergot alkaloid mycotoxins: physiological effects, metabolism and distribution of the residual toxin in mice
Authors: Reddy Priyanka , Hemsworth Joanne , Guthridge Kathryn M. , Vinh Antony , Vassiliadis Simone , Ezernieks Vilnis , Spangenberg German C. , Rochfort Simone J. 
Published: June 2020

AbstractThe complex ergot alkaloids, ergovaline and ergotamine, cause dysregulation of physiological functions, characterised by vasoconstriction as well as thermoregulatory and cardiovascular effects in grazing livestock. To assess the effect of the mycotoxins, blood pressure and heart rate of male mice were measured, and metabolite profiling undertaken to determine relative abundances of both ergotamine and its metabolic products in body and brain tissue. Ergotamine showed similar cardiovascular effects to ergovaline, causing elevations in blood pressure and reduced heart rate. Bradycardia was preserved at low-levels of ergovaline despite no changes in blood pressure. Ergotamine was identified in kidney, liver and brainstem but not in other regions of the brain, which indicates region-specific effects of the toxin. The structural configuration of two biotransformation products of ergotamine were determined and identified in the liver and kidney, but not the brain. Thus, the dysregulation in respiratory, thermoregulatory, cardiac and vasomotor function, evoked by ergot alkaloids in animals observed in various studies, could be partially explained by dysfunction in the autonomic nervous system, located in the brainstem.
A cross-reactive mouse monoclonal antibody against rhinovirus mediates phagocytosis in vitro
Authors: Behzadi Mohammad Amin , Choi Angela , Duehr James , Feyznezhad Roya , Upadhyay Chitra , Schotsaert Michael , Palese Peter , Nachbagauer Raffael 
Published: June 2020

AbstractRhinoviruses (RVs) are the main cause of the common cold worldwide. To date, more than 160 types of the virus have been recognized, categorized into three major species - A, B, and C. There are currently no approved vaccines available to prevent infection with RVs. To elicit antibodies against conserved regions located on capsid proteins of RV A viruses, mice were sequentially vaccinated with DNA plasmids encoding capsid proteins of different RV A types. After a final boost with whole virus, antibody-expressing hybridomas were generated. After isotyping, 11 monoclonal antibodies (mAbs) expressing an IgG subtype Fc-domain were selected for further expansion and purification. Three mAbs showed cross-reactivity against multiple strains of RV A viruses by ELISA, including strains A1A, A1B, A15, A16 and A49. Other mAbs had strain-specific binding patterns, with the majority of mAbs showing reactivity to RV-A15, the strain used for the final vaccination. We found that the RV-A15-specific mAbs, but not the cross-reactive mAbs, had neutralizing activity against RV-A15. An antibody dependent cellular phagocytosis (ADCP) assay revealed substantial ADCP activity for one of the cross-reactive mAbs. Epitope mapping of the neutralizing mAbs via escape mutant virus generation revealed a shared binding epitope on VP1 of RV-A15 for several neutralizing mAbs. The epitope of the ADCP-active, non-neutralizing mAb was determined by microarray analysis of peptides generated from the VP1 capsid protein. VP1-specific, cross-reactive antibodies, especially those with ADCP activity, could contribute to protection against RV infections.
Determining effects of water and nitrogen input on maize (Zea mays) yield, water- and nitrogen-use efficiency: A global synthesis
Authors: Li Yuan , Cui Song , Zhang Zhixin , Zhuang Kezhang , Wang Zhennan , Zhang Qingping 
Published: June 2020

AbstractA major challenge in maize (Zea mays) production is to achieve high grain yield (yield hereafter) by improving resource use efficiency. Using a dataset synthesized from 83 peer-reviewed articles, this study mainly investigated the effects of water and/or nitrogen (N) input on maize yield, water productivity (WP), and N use efficiency (NUE); and evaluated the effects caused by planting density, environmental (temperature, soil texture), and managerial factors (water and/or N input). The input of water increased maize yield, WP, and NUE only when the input was less than 314, 709, and 311 mm, respectively; input of N increased maize yield, WP, and NUE until input was greater than 250, 128, and 196 kg ha−1, respectively. Additionally, results of the mixed-effects model and random forest analysis suggested that mean annual temperature (MAT) was the most critical factor for narrowing gaps (between the actual and attainable variable, which was indicated as response ratio of the treatment relative to the control) of yield (RRY), WP (RRWP), and NUE (RRNUE), respectively. Specifically, RRY, RRWP, or RRNUE were negatively correlated to MAT when MAT was higher than 15 °C. Additionally, the structural equation model showed that water input and RRWP with the higher coefficient were more important than N input and RRNUE in improving RRY. These findings provide new insights into the causes and limitations of global maize production and offer some guidances for water and/or N managements.
The Prognostic Value of Deficient Mismatch Repair in Stage II–IVa Nasopharyngeal Carcinoma in the Era of IMRT
Authors: Chen Fang-ming , Zhang Yun-xiang , Li Xiu-feng , Gao Jian-fang , Ma Hao , Wang Xiao-li , Li Yang , Li Cheng , Zhang Ya-nan , Zhang Ya-ting , Kan Hong-xing , Li Han , Zhang Shi-geng , Hao Fu-rong , Wang Ming-chen 
Published: June 2020

AbstractIn the era of intensity-modulated radiotherapy (IMRT), it is important to analyse the prognostic value of deficient mismatch repair (dMMR) in nasopharyngeal carcinoma (NPC). In this study, in pretreatment biopsies of 69 patients with stage II–IVa NPC, the expression levels of MMR proteins, including MLH1, MSH2, MSH6 and PMS2, were assessed by immunohistochemistry (IHC). The median follow-up time was 37.5 months (3.1–87.4 months). 50.7% of cases (35/69) showed preserved expression of all 4 MMR proteins, which was interpreted as proficient mismatch repair (pMMR). Only 1.5% of cases (1/69) lost expression of all 4 MMR proteins, 26.1% of cases (18/69) have PMS2 loss alone and 21.7% of cases (15/69) lost expression of both PMS2 and MLH1. Thus, 49.3% of cases (34/69) lost expression of one or more MMR proteins, which was interpreted as dMMR. There was no significant difference (P > 0.05) in terms of sex, age, clinical stage, T category, N category or therapy regimens between the dMMR and pMMR groups. The multivariate Cox regression analysis revealed that dMMR was an independent significant prognostic factor for distant metastasis-free survival (DMFS) (dMMR vs pMMR: P = 0.01, HR = 0.25, 95% CI: 0.09~0.75). Therefore, NPC patients with dMMR had significantly superior DMFS compared with patients with pMMR. It can be expected that dMMR will become a new independent prognostic factor for NPC.
A Neural Network Approach to Identify the Peritumoral Invasive Areas in Glioblastoma Patients by Using MR Radiomics
Authors: Yan Jiun-Lin , Li Chao , van der Hoorn Anouk , Boonzaier Natalie R. , Matys Tomasz , Price Stephen J. 
Published: June 2020

AbstractThe challenge in the treatment of glioblastoma is the failure to identify the cancer invasive area outside the contrast-enhancing tumour which leads to the high local progression rate. Our study aims to identify its progression from the preoperative MR radiomics. 57 newly diagnosed cerebral glioblastoma patients were included. All patients received 5-aminolevulinic acid (5-ALA) fluorescence guidance surgery and postoperative temozolomide concomitant chemoradiotherapy. Preoperative 3 T MRI data including structure MR, perfusion MR, and DTI were obtained. Voxel-based radiomics features extracted from 37 patients were used in the convolutional neural network to train and as internal validation. Another 20 patients of the cohort were tested blindly as external validation. Our results showed that the peritumoural progression areas had higher signal intensity in FLAIR (p = 0.02), rCBV (p = 0.038), and T1C (p = 0.0004), and lower intensity in ADC (p = 0.029) and DTI-p (p = 0.001) compared to non-progression area. The identification of the peritumoural progression area was done by using a supervised convolutional neural network. There was an overall accuracy of 92.6% in the training set and 78.5% in the validation set. Multimodal MR radiomics can demonstrate distinct characteristics in areas of potential progression on preoperative MRI.
Recent effective population size in Eastern European plain Russians correlates with the key historical events
Authors: Yunusbaev Ural , Ionusbaev Arslan , Han Giyoun , Kwon Hyung Wook 
Published: June 2020

AbstractEffective population size reflects the history of population growth, contraction, and structuring. When the effect of structuring is negligible, the inferred trajectory of the effective population size can be informative about the key events in the history of a population. We used the IBDNe and DoRIS approaches, which exploit the data on IBD sharing between genomes, to reconstruct the recent effective population size in two population datasets of Russians from Eastern European plain: (1) ethnic Russians sampled from the westernmost part of Russia; (2) ethnic Russians, Bashkirs, and Tatars sampled from the Volga-Ural region. In this way, we examined changes in effective population size among ethnic Russians that reside in their historical area at the West of the plain, and that expanded eastward to come into contact with the indigenous peoples at the East of the plain. We compared the inferred demographic trajectories of each ethnic group to written historical data related to demographic events such as migration, war, colonization, famine, establishment, and collapse of empires. According to IBDNe estimations, 200 generations (~6000 years) ago, the effective size of the ancestral populations of Russians, Bashkirs, and Tatars hovered around 3,000, 30,000, and 8,000 respectively. Then, the ethnic Russians exponentially grew with increasing rates for the last 115 generations and become the largest ethnic group of the plain. Russians do not show any drop in effective population size after the key historical conflicts, including the Mongol invasion. The only exception is a moderate drop in the 17th century, which is well known in Russian history as The Smuta. Our analyses suggest a more eventful recent population history for the two small ethnic groups that came into contact with ethnic Russians in the Volga-Ural region. We found that the effective population size of Bashkirs and Tatars started to decrease during the time of the Mongol invasion. Interestingly, there is an even stronger drop in the effective population size that coincides with the expansion of Russians to the East. Thus, 15–20 generations ago, i.e. in the 16–18th centuries in the trajectories of Bashkirs and Tatars, we observe the bottlenecks of four and twenty thousand, respectively. Our results on the recent effective population size correlate with the key events in the history of populations of the Eastern European plain and have importance for designing biomedical studies in the region.