bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease
Authors: Lang Judith , Bohn Patrick , Bhat Hilal , Jastrow Holger , Walkenfort Bernd , Cansiz Feyza , Fink Julian , Bauer Michael , Olszewski Dominik , Ramos-Nascimento Ana , Duhan Vikas , Friedrich Sarah-Kim , Becker Katrin Anne , Krawczyk Adalbert , Edwards Michael J. , Burchert Andreas , Huber Magdalena , Friebus-Kardash Justa , Göthert Joachim R. , Hardt Cornelia , Probst Hans Christian , Schumacher Fabian , Köhrer Karl , Kleuser Burkhard , Babiychuk Eduard B. , Sodeik Beate , Seibel Jürgen , Greber Urs F. , Lang Philipp A. , Gulbins Erich , Lang Karl S. 
Published: March 2020

AbstractMacrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid ceramidase (aCDase) converts ceramide into sphingosine and increases the formation of sphingosine-rich intraluminal vesicles (ILVs). Once HSV-1 particles reach MVBs, sphingosine-rich ILVs bind to HSV-1 particles, which restricts fusion with the limiting endosomal membrane and prevents cellular infection. Lack of aCDase in macrophage cultures or in Asah1−/− mice results in replication of HSV-1 and Asah1−/− mice die soon after systemic or intravaginal inoculation. The treatment of macrophages with sphingosine enhancing compounds blocks HSV-1 propagation, suggesting a therapeutic potential of this pathway. In conclusion, aCDase loads ILVs with sphingosine, which prevents HSV-1 capsids from penetrating into the cytosol.
Aptamer-based optical manipulation of protein subcellular localization in cells
Authors: Xie Sitao , Du Yulin , Zhang Yu , Wang Zhimin , Zhang Dailiang , He Lei , Qiu Liping , Jiang Jianhui , Tan Weihong 
Published: March 2020

AbstractProtein-dominant cellular processes cannot be fully decoded without precise manipulation of their activity and localization in living cells. Advances in optogenetics have allowed spatiotemporal control over cellular proteins with molecular specificity; however, these methods require recombinant expression of fusion proteins, possibly leading to conflicting results. Instead of modifying proteins of interest, in this work, we focus on design of a tunable recognition unit and develop an aptamer-based near-infrared (NIR) light-responsive nanoplatform for manipulating the subcellular localization of specific proteins in their native states. Our results demonstrate that this nanoplatform allows photocontrol over the cytoplasmic-nuclear shuttling behavior of the target RelA protein (a member of the NF-κβ family), enabling regulation of RelA-related signaling pathways. With a modular design, this aptamer-based nanoplatform can be readily extended for the manipulation of different proteins (e.g., lysozyme and p53), holding great potential to develop a variety of label-free protein photoregulation strategies for studying complex biological events.
Ab initio electron-defect interactions using Wannier functions
Authors: Lu I-Te , Park Jinsoo , Zhou Jin-Jian , Bernardi Marco 
Published: March 2020

AbstractComputing electron–defect (e–d) interactions from first principles has remained impractical due to computational cost. Here we develop an interpolation scheme based on maximally localized Wannier functions (WFs) to efficiently computee–d interaction matrix elements. The interpolated matrix elements can accurately reproduce those computed directly without interpolation and the approach can significantly speed up calculations ofe–d relaxation times and defect-limited charge transport. We show example calculations of neutral vacancy defects in silicon and copper, for which we compute thee–d relaxation times on fine uniform and random Brillouin zone grids (and for copper, directly on the Fermi surface), as well as the defect-limited resistivity at low temperature. Our interpolation approach opens doors for atomistic calculations of charge carrier dynamics in the presence of defects.
Immunization of mice with chimeric antigens displaying selected epitopes confers protection against intestinal colonization and renal damage caused by Shiga toxin-producing Escherichia coli
Authors: Montero David A. , Del Canto Felipe , Salazar Juan C. , Céspedes Sandra , Cádiz Leandro , Arenas-Salinas Mauricio , Reyes José , Oñate Ángel , Vidal Roberto M. 
Published: March 2020

AbstractShiga toxin-producing Escherichia coli (STEC) cause diarrhea and dysentery, which may progress to hemolytic uremic syndrome (HUS). Vaccination has been proposed as a preventive approach against STEC infection; however, there is no vaccine for humans and those used in animals reduce but do not eliminate the intestinal colonization of STEC. The OmpT, Cah and Hes proteins are widely distributed among clinical STEC strains and are recognized by serum IgG and IgA in patients with HUS. Here, we develop a vaccine formulation based on two chimeric antigens containing epitopes of OmpT, Cah and Hes proteins against STEC strains. Intramuscular and intranasal immunization of mice with these chimeric antigens elicited systemic and local long-lasting humoral responses. However, the class of antibodies generated was dependent on the adjuvant and the route of administration. Moreover, while intramuscular immunization with the combination of the chimeric antigens conferred protection against colonization by STEC O157:H7, the intranasal conferred protection against renal damage caused by STEC O91:H21. This preclinical study supports the potential use of this formulation based on recombinant chimeric proteins as a preventive strategy against STEC infections.
Draft genomes of female and male turbot Scophthalmus maximus
Authors: Xu Xi-wen , Shao Chang-wei , Xu Hao , Zhou Qian , You Feng , Wang Na , Li Wen-long , Li Ming , Chen Song-lin 
Published: March 2020

AbstractTurbot (Scophthalmus maximus) is a commercially important flatfish species in aquaculture. It has a drastic sexual dimorphism, with females growing faster than males. In the present study, we sequenced and de novo assembled female and male turbot genomes. The assembled female genome was 568 Mb (scaffold N50, 6.2 Mb, BUSCO 97.4%), and the male genome was 584 Mb (scaffold N50, 5.9 Mb, BUSCO 96.6%). Using two genetic maps, we anchored female scaffolds representing 535 Mb onto 22 chromosomes. Annotation of the female anchored genome identified 87.8 Mb transposon elements and 20,134 genes. We identified 17,936 gene families, of which 369 gene families were flatfish specific. Phylogenetic analysis showed that the turbot, Japanese flounder and Chinese tongue sole form a clade that diverged from other teleosts approximately 78 Mya. This report of female and male turbot draft genomes and annotated genes provides a new resource for identifying sex determination genes, elucidating the evolution of adaptive traits in flatfish and developing genetic techniques to increase the sustainability of turbot aquaculture.
Variability in Language used on Social Media prior to Hospital Visits
Authors: Guntuku Sharath Chandra , Schwartz H. Andrew , Kashyap Adarsh , Gaulton Jessica S. , Stokes Daniel C. , Asch David A. , Ungar Lyle H. , Merchant Raina M. 
Published: March 2020

AbstractForecasting healthcare utilization has the potential to anticipate care needs, either accelerating needed care or redirecting patients toward care most appropriate to their needs. While prior research has utilized clinical information to forecast readmissions, analyzing digital footprints from social media can inform our understanding of individuals’ behaviors, thoughts, and motivations preceding a healthcare visit. We evaluate how language patterns on social media change prior to emergency department (ED) visits and inpatient hospital admissions in this case-crossover study of adult patients visiting a large urban academic hospital system who consented to share access to their history of Facebook statuses and electronic medical records. An ensemble machine learning model forecasted ED visits and inpatient admissions with out-of-sample cross-validated AUCs of 0.64 and 0.70 respectively. Prior to an ED visit, there was a significant increase in depressed language (Cohen’s d = 0.238), and a decrease in informal language (d = 0.345). Facebook posts prior to an inpatient admission showed significant increase in expressions of somatic pain (d = 0.267) and decrease in extraverted/social language (d = 0.357). These results are a first step in developing methods to utilize user-generated content to characterize patient care-seeking context which could ultimately enable better allocation of resources and potentially early interventions to reduce unplanned visits.
A novel hotspot specific isothermal amplification method for detection of the common PIK3CA p.H1047R breast cancer mutation
Authors: Kalofonou Melpomeni , Malpartida-Cardenas Kenny , Alexandrou George , Rodriguez-Manzano Jesus , Yu Ling-Shan , Miscourides Nicholas , Allsopp Rebecca , Gleason Kelly L. T. , Goddard Katie , Fernandez-Garcia Daniel , Page Karen , Georgiou Pantelis , Ali Simak , Coombes R. Charles , Shaw Jacqueline , Toumazou Christofer 
Published: March 2020

AbstractBreast cancer (BC) is a common cancer in women worldwide. Despite advances in treatment, up to 30% of women eventually relapse and die of metastatic breast cancer. Liquid biopsy analysis of circulating cell-free DNA fragments in the patients’ blood can monitor clonality and evolving mutations as a surrogate for tumour biopsy. Next generation sequencing platforms and digital droplet PCR can be used to profile circulating tumour DNA from liquid biopsies; however, they are expensive and time consuming for clinical use. Here, we report a novel strategy with proof-of-concept data that supports the usage of loop-mediated isothermal amplification (LAMP) to detect PIK3CA c.3140 A > G (H1047R), a prevalent BC missense mutation that is attributed to BC tumour growth. Allele-specific primers were designed and optimized to detect the p.H1047R variant following the USS-sbLAMP method. The assay was developed with synthetic DNA templates and validated with DNA from two breast cancer cell-lines and two patient tumour tissue samples through a qPCR instrument and finally piloted on an ISFET enabled microchip. This work sets a foundation for BC mutational profiling on a Lab-on-Chip device, to help the early detection of patient relapse and to monitor efficacy of systemic therapies for personalised cancer patient management.
Strain perceptibility of elements on the diffusion in Zr-based amorphous alloys
Authors: Lee A. Y. , Kim S. Y. , Jang H. , Kim Y. D. , Spieckermann F. , Wilde G. , Eckert J. , Lee M. H. 
Published: March 2020

AbstractWith the discovery of bulk metallic glasses (BMGs), there has been considerable interest in understanding their mechanical behavior. In spite of these previous observations on the relation between plastic deformation of metallic glasses and their diffusion behavior, a detailed understanding on the diffusion of BMGs is still unexplored. We evaluated the contribution of deformation-induced structural transformations (elastic, anelastic, viscoplastic or viscoelastic responsive and plastic strain) on the diffusion of Zr-based bulk metallic glasses in as-cast, elastostatically stressed and plastically deformed states. Experimental investigations of the diffusion process and the elemental distributions in the glassy alloy were performed following plastic deformation by multiple cold rolling and elastostatic cyclic compression, respectively. We compared the vacancy model and the transition state model to verify the diffusion mechanism in the deformed bulk metallic glass. The diffusion of tracer atoms, i.e., Fe, in the bulk metallic glass is affected by viscoelastic responsive strain governing the transition-state model. In contrast, the diffusion of constituent atoms, i.e., Ti, Zr, in the bulk metallic glass is dominantly affected by plastic strain governing the vacancy model. The results reveal that the diffusion behavior of bulk glassy alloys can be changed by variation of the constituent elements and applying different strain modes upon deformation.
Telomere length correlates with subtelomeric DNA methylation in long-term mindfulness practitioners
Authors: Mendioroz Maite , Puebla-Guedea Marta , Montero-Marín Jesús , Urdánoz-Casado Amaya , Blanco-Luquin Idoia , Roldán Miren , Labarga Alberto , García-Campayo Javier 
Published: March 2020

AbstractMindfulness and meditation techniques have proven successful for the reduction of stress and improvement in general health. In addition, meditation is linked to longevity and longer telomere length, a proposed biomarker of human aging. Interestingly, DNA methylation changes have been described at specific subtelomeric regions in long-term meditators compared to controls. However, the molecular basis underlying these beneficial effects of meditation on human health still remains unclear. Here we show that DNA methylation levels, measured by the Infinium HumanMethylation450 BeadChip (Illumina) array, at specific subtelomeric regions containing GPR31 and SERPINB9 genes were associated with telomere length in long-term meditators with a strong statistical trend when correcting for multiple testing. Notably, age showed no association with telomere length in the group of long-term meditators. These results may suggest that long-term meditation could be related to epigenetic mechanisms, in particular gene-specific DNA methylation changes at distinct subtelomeric regions.
Assessment of the human bone lacuno-canalicular network at the nanoscale and impact of spatial resolution
Authors: Yu Boliang , Pacureanu Alexandra , Olivier Cécile , Cloetens Peter , Peyrin Françoise 
Published: March 2020

AbstractRecently, increasing attention has been given to the study of osteocytes, the cells that are thought to play an important role in bone remodeling and in the mechanisms of bone fragility. The interconnected osteocyte system is deeply embedded inside the mineralized bone matrix and lies within a closely fitted porosity known as the lacuno-canalicular network. However, quantitative data on human samples remain scarce, mostly measured in 2D, and there are gaps to be filled in terms of spatial resolution. In this work, we present data on femoral samples from female donors imaged with isotropic 3D spatial resolution by magnified X-ray phase nano computerized-tomography. We report quantitative results on the 3D structure of canaliculi in human femoral bone imaged with a voxel size of 30 nm. We found that the lacuno-canalicular porosity occupies on average 1.45% of the total tissue volume, the ratio of the canalicular versus lacunar porosity is about 37.7%, and the primary number of canaliculi stemming from each lacuna is 79 on average. The examination of this number at different distances from the surface of the lacunae demonstrates branching in the canaliculi network. We analyzed the impact of spatial resolution on quantification by comparing parameters extracted from the same samples imaged with 120 nm and 30 nm voxel sizes. To avoid any bias related to the analysis region, the volumes at 120 nm and 30 nm were registered and cropped to the same field of view. Our results show that the measurements at 120 and 30 nm are strongly correlated in our data set but that the highest spatial resolution provides more accurate information on the canaliculi network and its branching properties.
Forecasting risk gene discovery in autism with machine learning and genome-scale data
Authors: Brueggeman Leo , Koomar Tanner , Michaelson Jacob J. 
Published: March 2020

AbstractGenetics has been one of the most powerful windows into the biology of autism spectrum disorder (ASD). It is estimated that a thousand or more genes may confer risk for ASD when functionally perturbed, however, only around 100 genes currently have sufficient evidence to be considered true “autism risk genes”. Massive genetic studies are currently underway producing data to implicate additional genes. This approach — although necessary — is costly and slow-moving, making identification of putative ASD risk genes with existing data vital. Here, we approach autism risk gene discovery as a machine learning problem, rather than a genetic association problem, by using genome-scale data as predictors to identify new genes with similar properties to established autism risk genes. This ensemble method, forecASD, integrates brain gene expression, heterogeneous network data, and previous gene-level predictors of autism association into an ensemble classifier that yields a single score indexing evidence of each gene’s involvement in the etiology of autism. We demonstrate that forecASD has substantially better performance than previous predictors of autism association in three independent trio-based sequencing studies. Studying forecASD prioritized genes, we show that forecASD is a robust indicator of a gene’s involvement in ASD etiology, with diverse applications to gene discovery, differential expression analysis, eQTL prioritization, and pathway enrichment analysis.
Superconductivity and Shubnikov - de Haas effect in polycrystalline Cd3As2 thin films
Authors: Oveshnikov Leonid N. , Davydov Alexander B. , Suslov Alexey V. , Ril’ Alexey I. , Marenkin Sergey F. , Vasiliev Alexander L. , Aronzon Boris A. 
Published: March 2020

AbstractIn this study we observed the reproducible superconducting state in Cd3As2 thin films without any external stimuli. Comparison with our previous results reveals similar qualitative behavior for films synthesized by different methods, while the difference in the values of the critical parameters clearly shows the possibility to control this state. The X-ray diffraction measurements demonstrate the presence of the tetragonal Cd3As2 crystal phase in studied films. Measurements of high-field magnetoresistance reveal pronounced Shubnikov - de Haas oscillations. The analysis of these oscillations suggests that, due to high carrier concentration in studied Cd3As2 films, the initial Dirac semimetal phase may be partially suppressed, which, however, does not contradict with possible topological nature of the observed superconductivity.
Novel RvD6 stereoisomer induces corneal nerve regeneration and wound healing post-injury by modulating trigeminal transcriptomic signature
Authors: Pham Thang L. , Kakazu Azucena H. , He Jiucheng , Jun Bokkyoo , Bazan Nicolas G. , Bazan Haydee E. P. 
Published: March 2020

AbstractThe high-density corneal innervation plays a pivotal role in sustaining the integrity of the ocular surface. We have previously demonstrated that pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) promotes corneal nerve regeneration; here, we report the mechanism involved and the discovery of a stereospecific Resolvin D6-isomer (RvD6si) that drives the process. RvD6si promotes corneal wound healing and functional recovery by restoring corneal innervation after injury. RvD6si applied to the eye surface elicits a specific transcriptome signature in the trigeminal ganglion (TG) that includes Rictor, the rapamycin-insensitive complex-2 of mTOR (mTORC2), and genes involved in axon growth, whereas genes related to neuropathic pain are decreased. As a result, attenuation of ocular neuropathic pain and dry eye will take place. Thus, RvD6si opens up new therapeutic avenues for pathologies that affect corneal innervation.
Fluorescence polarization assay to detect the presence of traces of ciprofloxacin
Authors: El Kojok Hiyam , El Darra Nada , Khalil Mahmoud , Capo Alessandro , Pennacchio Angela , Staiano Maria , Camarca Alessandra , D’Auria Sabato , Varriale Antonio 
Published: March 2020

AbstractDetection of ciprofloxacin residues in milk by sensitive and rapid methods is of great interest due to its use in the treatment of dairy livestock health. Current analytical approaches to antibiotics detection, are laboratory-based methods and they are time-consuming and require trained personnel. To cope this problem, we propose an assay, based on fluorescence polarization principle, able to detect the presence of ciprofloxacin in diluted milk sample without any pre-treatment. The proposed method is based on the use of ciprofloxacin-protein conjugate labeled with near infrared fluorescence dye, which upon binding to specific antibody causes an increase of the fluorescence polarization emission signal. The developed assay allows for the detection of ciprofloxacin at a concentration of 1ppb, which represents an amount lower than the maximum residual limit (MRL) of ciprofloxacin in milk, as set by the European Union regulation (100 ppb).
Associations between Central Obesity and Outcomes of Adult In-hospital Cardiac Arrest: A Retrospective Cohort Study
Authors: Wang Chih-Hung , Chang Wei-Tien , Huang Chien-Hua , Tsai Min-Shan , Lu Tsung-Chien , Chou Eric , Wu Yen-Wen , Chen Wen-Jone 
Published: March 2020

AbstractTo investigate the association between central obesity and outcomes following in-hospital cardiac arrest (IHCA). A single-centred retrospective study was conducted. Adult patients that experienced IHCA during 2006–2015 were screened. Body mass index (BMI) was calculated at hospital admission. Central obesity-related anthropometric parameters were measured by analysing computed tomography images. A total of 648 patients were included, with mean BMI of 23.0 kg/m2. The proportions of BMI-defined obesity in this cohort were underweight (13.1%), normal weight (41.4%), overweight (31.5%) and obesity (14.0%). The mean waist circumference was 85.9 cm with mean waist-to-height ratio (WHtR) of 0.53. The mean sagittal abdominal diameter was 21.2 cm with mean anterior and posterior abdominal subcutaneous adipose tissue (SAT) depths of 1.6 and 2.0 cm, respectively. Multivariate logistic regression analyses indicated BMI of 11.7–23.3 kg/m2 (odds ratio [OR]: 2.53, 95% confidence interval [CI]: 1.10–5.85; p-value = 0.03), WHtR of 0.49–0.59 (OR: 3.45, 95% CI: 1.56–7.65; p-value = 0.002) and anterior abdominal SAT depth <1.9 cm (OR: 2.84, 95% CI: 1.05–7.74; p-value = 0.04) were positively associated with the favourable neurological outcome. Central obesity was associated with poor IHCA outcomes, after adjusting for the effects of BMI.
Brownian fluctuations and hydrodynamics of a microhelix near a solid wall
Authors: Bianchi Silvio , Carmona Sosa Viridiana , Vizsnyiczai Gaszton , Di Leonardo Roberto 
Published: March 2020

AbstractWe combine two-photon lithography and optical tweezers to investigate the Brownian fluctuations and propeller characteristics of a microfabricated helix. From the analysis of mean squared displacements and time correlation functions we recover the components of the full mobility tensor. We find that Brownian motion displays correlations between angular and translational fluctuations from which we can directly measure the hydrodynamic coupling coefficient that is responsible for thrust generation. By varying the distance of the microhelices from a no-slip boundary we can systematically measure the effects of a nearby wall on the resistance matrix. Our results indicate that a rotated helix moves faster when a nearby no-slip boundary is present, providing a quantitative insight on thrust enhancement in confined geometries for both synthetic and biological microswimmers.