bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulmonary Hypertension Parameters Assessment by Electrocardiographically Gated Computed Tomography
Authors: Zhu Yinsu , Tang Xin , Wang Zhiyue , Wei Yongyue , Zhu Xiaomei , Liu Wangyan , Xu Yi , Tang Lijun , Shi Haibin 
Published: August 2018

Purpose:
Pulmonary hypertension (PH) parameters such as pulmonary artery or right ventricular size can be measured easily on computed tomography (CT). However, there are limited data on electrocardiographically (ECG) gated CT. We sought to determine age-specific and sex-specific normal reference values for PH parameters normalized by body surface area (BSA) using ECG-gated cardiac CT in a Chinese population.

Materials and Methods:
In total, we enrolled 519 non-PH patients undergoing ECG-gated CT coronary angiography and measured PH parameters, including main pulmonary artery (MPA) and right pulmonary artery (RPA) diameters and distension, the ratio of MPA to ascending aorta (AAO) diameter (MPA/AAO), and the ratio of right ventricular to left ventricular diameter (RV/LV). Maximum MPA and RPA diameters were also normalized to BSA (nMPA, nRPA).

Results:
Age, sex, BSA, and body mass index (BMI) were variably associated with PH parameters. Age was an independent predictor of all PH parameters. The maximum MPA diameter (26.5±2.7 mm), maximum RPA diameter (20.9±3.0 mm), nMPA (15.8±2.0 mm/m2), nRPA (12.4±2.0 mm/m2), and RV/LV (0.85±0.11) increased with age. MPA/AAO (0.80±0.10), MPA, and RPA distension (25.4%±7.1%; 23.3%±6.7%) correlated negatively with age. Although absolute MPA and RPA diameters were slightly larger in men, women had significantly larger nMPA and nRPA values. MPA and RPA sizes and RV/LV were correlated positively with BSA and BMI.

Conclusions:
Using ECG-gated cardiac CT, we determined the normal reference values of PH parameters for non-PH adult Chinese patients, and these values were variably influenced by age, sex, BSA, and BMI.
Chromatin architecture reorganisation during neuronal cell differentiation in Drosophila genome
Authors: Chathoth Keerthi T , Zabet Nicolae Radu 
Published: August 2018

ABSTRACTCompartmentalisation of the genome as topologically associating domains (TADs) may have regulatory role in development and cellular functioning, but the, mechanism involved in TAD establishment is still unclear. Here, we present the first high-resolution contact map ofDrosophila melanogasterneuronal cells (BG3) and identified different classes of TADs by comparing this to genome organisation in embryonic cells (Kc167). We find new rearrangements during differentiation in neuronal cells reflected as enhanced long-range interactions, which is supported by pronounced enrichment of CTCF at cell type specific borders. Furthermore, we show the presence of strong divergent transcription corroborated with RNA Polymerase II occupancy and increased DNA accessibility at the TAD borders. Interestingly, TAD borders that are specific to neuronal cells are enriched in enhancers controlled by neuronal specific transcription factors. Our results suggest that TADs are dynamic across developmental stages and reflect the interplay between insulators, transcriptional states and enhancer activities.
Catalytic promiscuity potentiated the divergence of new cytochrome P450 enzyme functions in cyanogenic defense metabolism
Authors: Barco Brenden , Zipperer Lara , Clay Nicole K. 
Published: August 2018

AbstractCytochrome P450 monooxygenases (P450s) constitute the largest metabolic enzyme family in plants, responsible for synthesizing hundreds of thousands of specialized metabolites with essential roles in chemical defenses against herbivores and pathogens (Banks et al., 2011; Nelson and Werck-Reichhart, 2011; Wurtzel and Kutchan, 2016). Substrate promiscuity has been documented to play a central role in the evolution of plant specialized metabolic enzymes (Weng et al., 2012; Leong and Last, 2017), however most plant P450s are highly substrate-specific (Verpoorte, 2013). Here, we show the rapid inversion of primary and weak secondary (promiscuous) catalytic activities between two distinct yet evolutionarily linked multifunctional P450s, CYP71A12 and CYP71A13, based on intramolecular epistasis of two amino acid residues under positive selection in CYP71A12. Furthermore, we uncover previously undocumented catalytic activity during the inversion as well as naturally occurring amino acid substitution patterns that could have been present in evolutionary intermediates between the two enzymes. Comparative expression profiling and homology modeling reveal that natural selection acted on the promoter of CYP71A13 and the substrate-recognition elements of CYP71A12 to improve the efficiencies of their promiscuous reactions. The rise in catalytic promiscuity potentiated the divergence of new P450 enzyme functions in cyanogenic defense metabolism. Directed evolution of promiscuous reactions is one of the core technologies underpinning the field of synthetic biology. Our results provide a more complete understanding of how natural selection uses promiscuous reactions to generate new enzymes in nature and chemical diversity in pathogen defense, as well as demonstrate a novel strategy for identifying their molecular origins in highly divergent, related enzymes.
IsoformSwitchAnalyzeR: Analysis of changes in genome-wide patterns of alternative splicing and its functional consequences
Authors: Vitting-Seerup Kristoffer , Sandelin Albin 
Published: August 2018

AbstractAlternative splicing is an important mechanism involved in both health and disease. Recent work highlights the importance of investigating genome-wide changes in patters of splicing and the subsequent functional consequences. Unfortunately current computational methods only support such analysis on a gene-by-gene basis. To fill this gap, we extended IsoformSwitchAnalyzeR thereby enabling analysis of genome-wide changes in both specific types of alternative splicing as well as the predicted functional consequences of the resulting isoform switches. As a case study, we analyzed RNA-seq data from The Cancer Genome Atlas and found systematic changes in both alternative splicing and the consequences of the associated isoform switches.AvailabilityWindows, Linux and Mac OS: http://bioconductor.org/packages/IsoformSwitchAnalyzeR.ContactKVS: k.vitting.seerup@gmail.com, AS: albin@binf.ku.dk
Optimizing non-invasive sampling of an infectious bat virus
Authors: Giles John R. , Peel Alison J. , Wells Konstans , Plowright Raina K. , McCallum Hamish , Restif Olivier 
Published: August 2018

AbstractNotable outbreaks of infectious viruses resulting from spillover events from bats have brought much attention to the ecological origins of bat-borne zoonoses, resulting in an increase in ecological and epidemiological studies on bat populations in Africa, Asia, and Australia. The aim of many of these studies is to identify new viral agents with field sampling methods that collect pooled urine samples from large plastic sheets placed under a bat roost. The efficiency of under-roost sampling also makes it an attractive method for gathering roost-level prevalence data. However, the method allows multiple individuals to contribute to a pooled sample, potentially introducing positive bias. To assess the ability of under-roost sampling to accurately estimate viral prevalence, we constructed a probabilistic model to explore the relationship between four sampling designs (quadrant, uniform, stratified, and random) and estimation bias. We modeled bat density and movement with a Poisson cluster process and spatial kernels, and simulated the four underroost sheet sampling designs by manipulating a spatial grid of hexagonal tiles. We performed global sensitivity analyses to identify major sources of estimation bias and provide recommendations for field studies that wish to estimate roost-level prevalence. We found that the quadrant-based design had a positive bias 5–7 times higher than other designs due to spatial auto-correlation among sampling sheets and clustering of bats in the roost. The sampling technique is therefore highly sensitive to viral presence; but lacks specificity, providing poor information regarding dynamics in viral prevalence. Given population sizes of 5000–14000, our simulation results indicate that using a stratified random design to collect 30–40 urine samples from 80–100 sheets, each with an area of 0.75–1m2, would provide sufficient estimation of true prevalence with minimum sampling bias and false negatives. However, acknowledging the general problem of data aggregation, we emphasize that robust inference of true prevalence from field data require information of underpinning roost sizes. Our findings refine our understanding of the underroost sampling technique with the aim of increasing its specificity, and suggest that the method be further developed as an efficient non-invasive sampling technique that provides roost-level estimates of viral prevalence within a bat population.
A modelling exercise to show why population models should incorporate distinct life histories of dispersers
Authors: Deere Jacques A. , van den Berg Ilona , Roth Gregory , Smallegange Isabel M. 
Published: August 2018

AbstractDispersal is an important form of movement influencing population dynamics, species distribution, and gene flow between populations. In population models, dispersal is often included in a simplified manner by removing a random proportion of the population. Many ecologists now argue that models should be formulated at the level of individuals instead of the population-level. To fully understand the effects of dispersal on natural systems, it is therefore necessary to incorporate individual-level differences in dispersal behaviour in population models. Here we parameterised an integral projection model (IPM), which allows for studying how individual life histories determine population-level processes, using bulb mites,Rhizoglyphus robini, to assess to what extent dispersal expression (frequency of individuals in the dispersal stage) and dispersal probability affect the proportion of dispersers and natal population growth rate. We find that allowing for life-history differences between resident phenotypes and disperser phenotypes shows that multiple combinations of dispersal probability and dispersal expression can produce the same proportion of leaving individuals. Additionally, a given proportion of dispersing individuals results in different natal population growth rates. The results highlight that dispersal life histories, and the frequency with which disperser phenotypes occur in the natal population, significantly affect population-level processes. Thus, biological realism of dispersal population models can be increased by incorporating the typically observed life history differences between resident phenotypes and disperser phenotypes, and we here present a methodology to do so.
Coding of whisker motion across the mouse face
Authors: Severson Kyle S. , Xu Duo , Yang Hongdian , O’Connor Daniel H. 
Published: August 2018

AbstractHaptic perception synthesizes touch with proprioception, or sense of body position. Humans and mice alike experience rich active touch of the face. Because most facial muscles lack proprioceptor endings, the sensory basis of facial proprioception remains unsolved. Facial proprioception may instead rely on mechanoreceptors that encode both touch and self-motion. In rodents, whisker mechanoreceptors provide a signal that informs the brain about whisker position. Whisking involves coordinated orofacial movements, so mechanoreceptors innervating facial regions other than whiskers could also provide information about whisking. To define all sources of sensory information about whisking available to the brain, we recorded spikes from mechanoreceptors innervating diverse parts of the face. Whisker motion was encoded best by whisker mechanoreceptors, but also by those innervating whisker pad hairy skin and supraorbital vibrissae. Redundant self-motion responses may provide the brain with a stable proprioceptive signal despite mechanical perturbations such as whisker growth and active touch.
Rapid heuristic inference of antibiotic resistance and susceptibility by genomic neighbor typing
Authors: Břinda Karel , Callendrello Alanna , Ma Kevin C. , MacFadden Derek R , Charalampous Themoula , Lee Robyn S , Cowley Lauren , Wadsworth Crista B , Grad Yonatan H , Kucherov Gregory , O’Grady Justin , Baym Michael , Hanage William P 
Published: August 2018

AbstractSurveillance of drug-resistant bacteria is essential for healthcare providers to deliver effective empiric antibiotic therapy. However, traditional molecular epidemiology does not typically occur on a timescale that could impact patient treatment and outcomes. Here we present a method called ‘genomic neighbor typing’ for inferring the phenotype of a bacterial sample by identifying its closest relatives in a database of genomes with metadata. We show that this technique can infer antibiotic susceptibility and resistance for both S. pneumoniae and N. gonorrhoeae. We implemented this with rapid k-mer matching, which, when used on Oxford Nanopore MinION data, can run in real time. This resulted in determination of resistance within ten minutes (sens/spec 91%/100% for S. pneumoniae and 81%/100% N. gonorrhoeae from isolates with a representative database) of sequencing starting, and for clinical metagenomic sputum samples (75%/100% for S. pneumoniae), within four hours of sample collection. This flexible approach has wide application to pathogen surveillance and may be used to greatly accelerate appropriate empirical antibiotic treatment.
A model for physiological transmembrane transport derived from thermodynamical principles
Authors: Herrera-Valdez Marco Arieli 
Published: August 2018

AbstractA generic formulation for both passive and active transmembrane transport is derived from basic thermodynamical principles. The derivation takes into account the energy required for the motion of molecules across membranes, and includes the possibility of modeling asymmetric flow. Transmembrane currents can then be described by the generic model in the case of electrogenic flow. As it is desirable in new models, it is possible to derive other well known expressions for transmembrane currents as particular cases of the generic formulation. For instance, the conductance-based formulation for current turns out to be a linear approximation of the generic current. Also, under suitable assumptions, other formulas for current based on electrodiffusion, like the constant field approximation by Goldman, can also be recovered from the generic formulation. The applicability of the generic formulations is illustrated first with fits to existing data, and after, with models of transmembrane potential dynamics for pacemaking cardiocytes and neurons. The generic formulations presented here provide a common ground for the biophysical study of physiological phenomena that depend on transmembrane transport.
Sleep regulates visual selective attention inDrosophila
Authors: Kirszenblat Leonie , Ertekin Deniz , Goodsell Joseph , Zhou Yanqiong , Shaw Paul J , Swinderen Bruno van 
Published: August 2018

AbstractAlthough sleep-deprivation is known to impair attention in humans and other mammals, the underlying reasons are not well understood, and whether similar effects are present in non-mammalian species is not known. We therefore sought to investigate whether sleep is important for optimising attention in an invertebrate species, the genetic modelDrosophila melanogaster. We developed a high-throughput paradigm to measure visual attention in freely-walkingDrosophila, using competing foreground/background visual stimuli. We found that whereas sleep-deprived flies could respond normally to either stimulus alone, they were more distracted by background cues in a visual competition task. Other stressful manipulations such as starvation, heat exposure, and mechanical stress had no effects on visual attention in this paradigm. In contrast to sleep-deprivation, providing additional sleep using the GABA-A agonist 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol (THIP) did not affect attention in wild-type flies, but significantly improved attention in the learning mutantdunce. Our results reveal a key function of sleep in optimising attention processes inDrosophila, and establish a behavioural paradigm that can be used to explore the molecular mechanisms involved.Summary statementSleep deprivation specifically impairs visual selective attention in fruit flies, without affecting behavioural responses to simple visual stimuli.
Fusion pore regulation by Epac2/cAMP controls cargo release during insulin exocytosis
Authors: Gucek Alenka , Gandasi Nikhil R , Omar-Hmeadi Muhmmad , Bakke Marit , Døskeland Stein O. , Tengholm Anders , Barg Sebastian 
Published: August 2018

AbstractRegulated exocytosis establishes a narrow fusion pore as the initial aqueous connection to the extracellular space, through which small transmitter molecules such as ATP can exit. Co-release of larger peptides and hormones like insulin requires further expansion of the pore. There is evidence that pore expansion is regulated and can fail in type-2 diabetes and neurodegenerative disease. Here we report that the cAMP-sensor Epac2 (Rap-GEF4) controls fusion pore behavior by acutely recruiting two pore-restricting proteins, amisyn and dynamin-1, to the exocytosis site in insulin-secreting beta-cells. cAMP elevation leads to pore expansion and peptide release, but not when Epac2 is inactivated pharmacologically or in Epac2-/- mice. Conversely, overexpression of Epac2 impedes pore expansion. Widely used antidiabetic drugs (GLP-1 agonists and sulfonylureas) activate this pathway and thereby paradoxically restrict hormone release. We conclude that Epac2/cAMP controls fusion pore expansion and thus the balance of hormone and transmitter release during insulin granule exocytosis.
Automated literature mining and hypothesis generation through a network of Medical Subject Headings
Authors: Wilson Stephen Joseph , Wilkins Angela Dawn , Holt Matthew V. , Choi Byung Kwon , Konecki Daniel , Lin Chih-Hsu , Koire Amanda , Chen Yue , Kim Seon-Young , Wang Yi , Wastuwidyaningtyas Brigitta Dewi , Qin Jun , Donehower Lawrence Allen , Lichtarge Olivier 
Published: August 2018

ABSTRACTThe scientific literature is vast, growing, and increasingly specialized, making it difficult to connect disparate observations across subfields. To address this problem, we sought to develop automated hypothesis generation by networking at scale the MeSH terms curated by the National Library of Medicine. The result is a Mesh Term Objective Reasoning (MeTeOR) approach that tallies associations among genes, drugs and diseases from PubMed and predicts new ones.Comparisons to reference databases and algorithms show MeTeOR tends to be more reliable. We also show that many predictions based on the literature prior to 2014 were published subsequently. In a practical application, we validated experimentally a surprising new association found by MeTeOR between novel Epidermal Growth Factor Receptor (EGFR) associations and CDK2. We conclude that MeTeOR generates useful hypotheses from the literature (http://meteor.lichtargelab.org/).AUTHOR SUMMARYThe large size and exponential expansion of the scientific literature forms a bottleneck to accessing and understanding published findings. Manual curation and Natural Language Processing (NLP) aim to address this bottleneck by summarizing and disseminating the knowledge within articles as key relationships (e.g. TP53 relates to Cancer). However, these methods compromise on either coverage or accuracy, respectively. To mitigate this compromise, we proposed using manually-assigned keywords (MeSH terms) to extract relationships from the publications and demonstrated a comparable coverage but higher accuracy than current NLP methods. Furthermore, we combined the extracted knowledge with semi-supervised machine learning to create hypotheses to guide future work and discovered a direct interaction between two important cancer genes.
Switch-Like Phosphorylation of WRN Integrates End-Resection with RAD51 Metabolism at Collapsed Replication Forks
Authors: Palermo Valentina , Malacaria Eva , Semproni Maurizio , Perdichizzi Benedetta , Valenzisi Pasquale , Sanchez Massimo , Marini Federica , Pellicioli Achille , Franchitto Annapaola , Pichierri Pietro 
Published: August 2018

ABSTRACTReplication-dependent DNA double-strand breaks are harmful lesions preferentially repaired by homologous recombination; a process that requires processing of DNA ends to allow RAD51-mediated strand invasion. End-resection and subsequent repair are two intertwined processes, but the mechanism underlying their execution is still poorly appreciated. The WRN helicase is one of the crucial factors for the end-resection and is instrumental to select the proper repair pathway. Here, we reveal that ordered phosphorylation of WRN by the CDK1, ATM and ATR kinases define a complex regulatory layer that is essential for correct long-range end-resection connecting it to repair by homologous recombination. We establish that long-range end-resection requires an ATM-dependent phosphorylation of WRN at Ser1058 and that phosphorylation at Ser1141, together with dephosphorylation at the CDK1 site Ser1133, is needed for the correct metabolism of RAD51 foci and RAD51-dependent repair. Collectively, our findings suggest that regulation of WRN by multiple kinases functions as molecular switch to allow a timely execution of end-resection and repair at replication-dependent DNA double-strand breaks.