bluuebunny/crossref_metadata_2025_split huggingface dataset:
The glycoprotease CpaA secreted by medically relevantAcinetobacterspecies targets multipleO-linked host glycoproteins
Authors: Haurat M. Florencia , Scott Nichollas E. , Di Venanzio Gisela , Lopez Juvenal , Pluvinage Benajmin , Boraston Alisdair B. , Ferracane Michael J. , Feldman Mario F. 
Published: July 2020

ABSTRACTGlycans decorate proteins and affect their biological function, including protection against proteolytic degradation. However, pathogenic, and commensal bacteria have evolved specific glycoproteases that overcome the steric impediment posed by carbohydrates, cleaving glycoproteins precisely at their glycosylation site(s). Medically relevantAcinetobacterstrains employ their type II secretion system (T2SS) to secrete the glycoprotease CpaA, which contributes to virulence. Previously, CpaA was shown to cleave twoO-linked glycoproteins, factors V and XII, leading to reduced blood coagulation. In this work, we show that CpaA cleaves a broader range ofO-linked human glycoproteins, including several glycoproteins involved in complement activation, such as CD55 and CD46. However, only CD55 was removed from the cell surface, while CD46 remained unaltered during theA. nosocomialisinfection assay. We show that CpaA has a unique consensus target sequence that consists of a glycosylated serine or threonine residue after a proline residue (P-S/T), and its activity is not affected by sialic acids. Molecular modeling and mutagenesis analysis of CpaA suggest that the indole ring of Trp493 and the ring of the Pro residue in the substrate form a key interaction that contributes to CpaA sequence selectivity. Similar bacterial glycoproteases have recently gained attention as tools for proteomic analysis of human glycoproteins, and CpaA appears to be a robust and attractive new component of the glycoproteomics toolbox. Combined, our work provides insight into the function and possible application of CpaA, a member of a widespread class of broad-spectrum bacterial glycoproteases involved in host-pathogen interactions.IMPORTANCECpaA is a glycoprotease expressed by members of theAcinetobacter baumannii-calcoaceticuscomplex and it is the firstbona fidesecreted virulence factor identified in these species. Here, we show that CpaA cleaves multiple targets precisely atO-glycosylation sites preceded by a Pro residue. This feature, together with the observation that sialic acid does not impact CpaA activity, makes of this enzyme an attractive tool for the analysis ofO-linked human protein for biotechnical and diagnostic purposes. Previous work identified proteins involved in blood coagulation as targets of CpaA. Our work broadens the set of targets of CpaA, pointing towards additional roles in bacteria-host interactions. We propose that CpaA belongs to an expanding class of functionally-defined glycoproteases that targets multipleO-linked host glycoproteins.
Associations of severe COVID-19 with polypharmacy in the REACT-SCOT case-control study
Authors: McKeigue Paul M , Kennedy Sharon , Weir Amanda , Bishop Jen , McGurnaghan Stuart J , McAllister David , Robertson Chris , Wood Rachael , Lone Nazir , Murray Janet , Caparrotta Thomas M , Smith-Palmer Alison , Goldberg David , McMenamin Jim , Ramsay Colin , Guthrie Bruce , Hutchinson Sharon , Colhoun Helen M 
Published: July 2020

AbstractObjectivesTo investigate the relation of severe COVID-19 to prior drug prescribing.DesignMatched case-control study (REACT-SCOT) based on record linkage to hospital discharges since June 2015 and dispensed prescriptions issued in primary care during the last 240 days.SettingScottish population.Main outcome measureSevere COVID-19, defined by entry to critical care or fatal outcome.ParticipantsAll 4272 cases of severe COVID-19 in Scotland since the start of the epidemic, with 36948 controls matched for age, sex and primary care practice.ResultsSevere COVID-19 was strongly associated with the number of non-cardiovascular drug classes dispensed. This association was strongest in those not resident in care homes, in whom the rate ratio (95% CI) associated with dispensing of 12 or more drug classes versus none was 10.8 (8.7, 13.2), and was not accounted for by treatment of conditions designated as conferring increased risk. Of 17 drug classes postulated at the start of the epidemic to be “medications compromising COVID”, all were associated with increased risk of severe COVID-19. The largest effect was for antipsychotic agents: rate ratio 4.14 (3.39, 5.07). Other drug classes with large effects included proton pump inhibitors (rate rato 2.19 (1.70, 2.80) for >= 2 defined daily doses/day), opioids (3.62 (2.65, 4.94) for >= 50 mg morphine equivalent/day) and gabapentinoids. These associations persisted after adjusting for covariates, and were stronger with recent than with non-recent exposure.ConclusionsSevere COVID-19 is associated with polypharmacy and with drugs that cause sedation, respiratory depression or dyskinesia, have anticholinergic effects or affect the gastrointestinal system. These associations are not easily explained by co-morbidity. Although the evidence for causality is not conclusive, these results support existing guidance on reducing overprescribing of these drug classes and limiting inappropriate polypharmacy as a potential means of reducing COVID-19 risk.RegistrationENCEPP number EUPAS35558What is already known on this topicTwo previous studies have examined the relationship of severe COVID-19 to drugs for the cardiovascular system. This is the first systematic study of the relationship of severe COVID-19 to prior drug prescribing.What this study addsSevere COVID-19 is associated with polypharmacy and with drugs that cause sedation, respiratory depression or dyskinesia, have anticholinergic effects or affect the gastrointestinal system. These associations are not easily explained by co-morbidity. These results support earlier warnings that these drug classes that these drugs might increase susceptibility to COVID-19, and reinforce existing guidance on reducing overprescribing of these drug classes.
Dual-purpose isocyanides produced byAspergillus fumigatuscontribute to cellular copper sufficiency and exhibit antimicrobial activity
Authors: Raffa Nicholas , Won Tae Hyung , Sukowaty Andrew , Candor Kathleen , Cui Chengsen , Halder Saayak , Dai Mingji , Figueroa Julio Landero , Schroeder Frank C. , Keller Nancy 
Published: July 2020

AbstractThe maintenance of sufficient but non-toxic pools of metal micronutrients is accomplished through diverse homeostasis mechanisms in fungi. Siderophores play a well-established role for iron homeostasis; however, no copper-binding analogs have been found in fungi. Here we demonstrate that inAspergillus fumigatusisocyanides derived from thexanbiosynthetic gene cluster (BGC) bind copper, impact cellular copper content, and have significant metal-dependent antimicrobial properties.xanBGC-derived isocyanides are secreted and bind copper as visualized by a chrome azurol S (CAS) assay and inductively coupled plasma-mass spectrometry (ICP-MS) analysis ofA. fumigatusintracellular copper pools demonstrated a role forxancluster metabolites in the accumulation of copper.A. fumigatuscoculture withA. nidulans, Candida albicansand a variety of pathogenic bacteria establish copper-dependent antimicrobial properties ofxanBGC metabolites including inhibition of laccase activity. Similarly, inhibition ofPseudomonas aeruginosaby low concentrations of thexanisocyanide xanthocillin was copper-dependent. Other metals also reduced xanthocillin’s antimicrobial properties, but less efficiently than copper. As variations of thexanBGC exist in other filamentous fungi, we suggest that xanthocillin-like natural products represent a first example for fungal small molecules that serve to maintain copper sufficiency and mediate interactions with competing microbes.SignificanceMetal homeostasis is an integral part of metabolism for any organism. A vast array of small molecules are already known to mediate metal homeostasis in fungi and bacteria; however, unlike their bacterial counterparts, to-date there are no known fungal small molecules that function to maintain copper homeostasis. Discovery of copper binding small molecules produced byA. fumigatusgives insight into mechanisms other than the extensively studied copper transporters or metalloproteins for how fungi can regulate copper. This has important ecological implications as securing scarce nutrients is central for fitness and survival. Additionally, studying this mechanism inA. fumigatusprovides a basis for investigation of copper regulation pathways in other fungi.
The genetic architecture of the sexually selected sword ornament and its evolution in hybrid populations
Authors: Powell Daniel L. , Payne Cheyenne , Keegan Mackenzie , Banerjee Shreya M. , Cui Rongfeng , Andolfatto Peter , Schumer Molly , Rosenthal Gil G. 
Published: July 2020

AbstractBiologists since Darwin have been fascinated by the evolution of sexually selected ornaments, particularly those that reduce viability. Uncovering the genetic architecture of these traits is key to understanding how they evolve and are maintained. Here, we investigate the genetic architecture of a sexually selected ornament, the “sword” fin extension that characterizes many species of swordtail fish (Xiphophorus). Using sworded and swordless sister species ofXiphophorus, we generated a mapping population and show that the sword ornament is polygenic – with ancestry across the genome explaining substantial variation in the trait. After accounting for the impacts of genome-wide ancestry, we identify one major effect QTL that explains ∼5% of the overall variation in the trait. Using a series of approaches, we narrow this large QTL interval to a handful of likely candidate genes, including the genesp8. Notably,sp8plays a regulatory role in fin regeneration and harbors several derived substitutions that are predicted to impact protein function in the species that has lost the sword ornament. Furthermore, we find evidence of selection on ancestry atsp8in four natural hybrid populations, consistent with selection against the sword in these populations.
Computer vision approach to characterize size and shape phenotypes of horticultural crops using high-throughput imagery
Authors: Haque Samiul , Lobaton Edgar , Nelson Natalie , Yencho G Craig , Pecota Kenneth V , Mierop Russell , Kudenov Michael W , Boyette Mike , Williams Cranos M 
Published: July 2020

AbstractFor many horticultural crops, variation in quality (e.g., shape and size) contribute significantly to the crop’s market value. Metrics characterizing less subjective harvest quantities (e.g., yield and total biomass) are routinely monitored. In contrast, metrics quantifying more subjective crop quality characteristics such as ideal size and shape remain difficult to characterize objectively at the production-scale due to the lack of modular technologies for high-throughput sensing and computation. Several horticultural crops are sent to packing facilities after having been harvested, where they are sorted into boxes and containers using high-throughput scanners. These scanners capture images of each fruit or vegetable being sorted and packed, but the images are typically used solely for sorting purposes and promptly discarded. With further analysis, these images could offer unparalleled insight on how crop quality metrics vary at the industrial production-scale and provide further insight into how these characteristics translate to overall market value. At present, methods for extracting and quantifying quality characteristics of crops using images generated by existing industrial infrastructure have not been developed. Furthermore, prior studies that investigated horticultural crop quality metrics, specifically of size and shape, used a limited number of samples, did not incorporate deformed or non-marketable samples, and did not use images captured from high-throughput systems. In this work, using sweetpotato (SP) as a use case, we introduce a computer vision algorithm for quantifying shape and size characteristics in a high-throughput manner. This approach generates 3D model of SPs from two 2D images captured by an industrial sorter 90 degrees apart and extracts 3D shape features in a few hundred milliseconds. We applied the 3D reconstruction and feature extraction method to thousands of image samples to demonstrate how variations in shape features across sweetptoato cultivars can be quantified. We created a sweetpotato shape dataset containing sweetpotato images, extracted shape features, and qualitative shape types (U.S. No. 1 or Cull). We used this dataset to develop a neural network-based shape classifier that was able to predict Cull vs. U.S. No. 1 sweetpotato with 84.59% accuracy. In addition, using univariate Chi-squared tests and random forest, we identified the most important features for determining qualitative shape (U.S. No. 1 or Cull) of the sweetpotatoes. Our study serves as the first step towards enabling big data analytics for sweetpotato agriculture. The methodological framework is readily transferable to other horticultural crops, particularly those that are sorted using commercial imaging equipment.
Inducing highly physiologically relevant phenotypes of human vascular smooth muscle cells via 3D printing
Authors: Zhu Peiran , Li Xuzhao , Xin Wang , Wang Menglin , Yin Chengzhen , Li Jinze , Chen Hangyu , Zhu Hengjia , Sun Yubing , Jia Jiemin , Zhou Nanjia 
Published: July 2020

ABSTRACTVascular smooth muscle cells (vSMCs) are one of the essential cell types in blood vessel walls. A significant vSMC phenotype characteristic is that they collectively wrap around the outer layer of the healthy blood vessels with spindle-like morphology and help maintain the vascular tones and regulate the blood flow. Both physiological and biomedical research are impeded by the standard 2D cell culture approaches which do not createin vivolike microenvironment. Here, we systematically investigated the vSMCs culturing within 3D printed geometrical constraints and on printed microfilaments. Based on these models, we demonstrate a simple bioprinting approach for fast manufacturing vessel architectures with micro-grooved surfaces for vSMCs alignment. We validated that the vSMCs cultured on the printed vessel with microfilaments (VWMF) present a more physiologically relevant morphological phenotype and gene expression profile, and they are considerably more active in wound healing and ischemia than conventional planarly cultured vSMCs.
Transcriptomic Response of Brain Tissue to Focused Ultrasound-Mediated Blood-Brain Barrier Disruption Depends Strongly on Anesthesia
Authors: Mathew A.S. , Gorick C.M. , Thim E.A. , Garrison W.J. , Klibanov A.L. , Miller G.W. , Sheybani N.D. , Price R.J. 
Published: July 2020

AbstractFocused ultrasound (FUS) mediated blood brain barrier disruption (BBBD) is a promising strategy for the targeted delivery of systemically-administered therapeutics to the central nervous system (CNS). Pre-clinical investigations of BBBD have been performed on different anesthetic backgrounds; however, the potential influence of the choice of anesthetic on the molecular response to BBBD is unknown, despite its potential to critically affect interpretation of experimental therapeutic outcomes. Here, using bulk RNA sequencing approaches, we comprehensively examined the transcriptomic response of both normal brain tissue and brain tissue exposed to FUS-induced BBBD in mice anesthetized with either isoflurane with medical air (Iso) or ketamine/dexmedetomidine (KD). In normal murine brain tissue, Iso alone elicited minimal differential gene expression (DGE) and repressed pathways associated with neuronal signaling. KD alone, however, led to massive DGE and enrichment of pathways associated with protein synthesis. In brain tissue exposed to BBBD (1 MHz, 0.5 Hz pulse repetition frequency, 0.4 MPa peak-negative pressure), we systematically evaluated the relative effects of anesthesia, microbubbles, and FUS on the transcriptome. Of particular interest, we observed that gene sets associated with sterile inflammatory responses and cell-cell junctional activity were induced by BBBD, regardless of the choice of anesthesia. Meanwhile, gene sets associated with metabolism, platelet activity, tissue repair, and signaling pathways, were differentially affected by BBBD, with a strong dependence on the anesthetic. We conclude that the underlying transcriptomic response to FUS-mediated BBBD may be powerfully influenced by anesthesia. These findings raise considerations for the translation of FUS-BBBD delivery approaches that impact, in particular, metabolism, tissue repair, and intracellular signaling.
Two-dimensional video-based analysis of human gait using pose estimation
Authors: Stenum Jan , Rossi Cristina , Roemmich Ryan T. 
Published: July 2020

ABSTRACTWalking is the primary mode of human locomotion. Accordingly, people have been interested in studying human gait since at least the fourth century BC. Human gait analysis is now common in many fields of clinical and basic research, but gold standard approaches – e.g., three-dimensional motion capture, instrumented mats or footwear, and wearables – are often expensive, immobile, data-limited, and/or require specialized equipment or expertise for operation. Recent advances in video-based pose estimation have suggested exciting potential for analyzing human gait using only two-dimensional video inputs collected from readily accessible devices (e.g., smartphones, tablets). However, we currently lack: 1) data about the accuracy of video-based pose estimation approaches for human gait analysis relative to gold standard measurement techniques and 2) an available workflow for performing human gait analysis via video-based pose estimation. In this study, we compared a large set of spatiotemporal and sagittal kinematic gait parameters as measured by OpenPose (a freely available algorithm for video-based human pose estimation) and three-dimensional motion capture from trials where healthy adults walked overground. We found that OpenPose performed well in estimating many gait parameters (e.g., step time, step length, sagittal hip and knee angles) while some (e.g., double support time, sagittal ankle angles) were less accurate. We observed that mean values for individual participants – as are often of primary interest in clinical settings – were more accurate than individual step-by-step measurements. We also provide a workflow for users to perform their own gait analyses and offer suggestions and considerations for future approaches.
Causal evidence for a double dissociation between object- and scene-selective regions of visual cortex: A pre-registered TMS replication study
Authors: Wischnewski Miles , Peelen Marius V. 
Published: July 2020

AbstractNatural scenes are characterized by individual objects as well as by global scene properties such as spatial layout. Functional neuroimaging research has shown that this distinction between object and scene processing is one of the main organizing principles of human high-level visual cortex. For example, object-selective regions, including the lateral occipital complex (LOC), were shown to represent object content (but not scene layout), while scene-selective regions, including the occipital place area (OPA), were shown to represent scene layout (but not object content). Causal evidence for a double dissociation between LOC and OPA in representing objects and scenes is currently limited, however. One TMS experiment, conducted in a relatively small sample (N=13), reported an interaction between LOC and OPA stimulation and object and scene recognition performance (Dilks et al., 2013). Here, we present a high-powered pre-registered replication of this study (N=72, including male and female human participants), using group-average fMRI coordinates to target LOC and OPA. Results revealed unambiguous evidence for a double dissociation between LOC and OPA: Relative to vertex stimulation, TMS over LOC selectively impaired the recognition of objects, while TMS over OPA selectively impaired the recognition of scenes. Furthermore, we found that these effects were stable over time and consistent across individual objects and scenes. These results show that LOC and OPA can be reliably and selectively targeted with TMS, even when defined based on group-average fMRI coordinates. More generally, they support the distinction between object and scene processing as an organizing principle of human high-level visual cortex.Significance StatementOur daily-life environments are characterized both by individual objects and by global scene properties. The distinction between object and scene processing features prominently in visual cognitive neuroscience, with fMRI studies showing that this distinction is one of the main organizing principles of human high-level visual cortex. However, causal evidence for the selective involvement of object- and scene-selective regions in processing their preferred category is less conclusive. Here, testing a large sample (N=72) using an established paradigm and a pre-registered protocol, we found that TMS over object-selective cortex (LOC) selectively impaired object recognition while TMS over scene-selective cortex (OPA) selectively impaired scene recognition. These results provide conclusive causal evidence for the distinction between object and scene processing in human visual cortex.
Temporally and Spatially Partitioned Neuropeptide Release from Individual Clock Neurons
Authors: Klose Markus K. , Bruchez Marcel P. , Deitcher David L. , Levitan Edwin S. 
Published: July 2020

Neuropeptides control rhythmic behaviors, but the timing and location of their release within circuits is unknown. Here imaging in the brain shows that synaptic neuropeptide release byDrosophilaclock neurons is diurnal, peaking at times of day that were not anticipated by prior electrical and Ca2+data. Furthermore, hours before peak synaptic neuropeptide release, neuropeptide release occurs at the soma, a neuronal compartment that has not been implicated in peptidergic transmission. The timing disparity between release at the soma and terminals results from independent and compartmentalized mechanisms for daily rhythmic release: consistent with conventional electrical activity-triggered synaptic transmission, terminals require Ca2+influx, while somatic neuropeptide release is triggered by the biochemical signal IP3. Upon disrupting the somatic mechanism, the rhythm of terminal release and locomotor activity period are unaffected, but the number of flies with rhythmic behavior and sleep-wake balance are reduced. These results support the conclusion that somatic neuropeptide release controls specific features of clock neuron dependent behaviors. Thus, compartment specific mechanisms within individual clock neurons produce temporally and spatially partitioned neuropeptide release to expand the peptidergic connectome underlying daily rhythmic behaviors.Significance StatementIt is believed that electrical activity simultaneously stimulates widespread release sites in single neurons to elicit neuropeptide dependent behaviors. However, optically detecting neuropeptide release in the intact brain shows that clock neurons release neuropeptides from different sites at different times of the day. This is possible because one neuronal compartment, the soma, uses biochemical signaling instead of electrical activity to evoke release. Disrupting somatic release affects specific features of circadian locomotor activity and sleep. Thus, neuropeptide release is elicited by independent triggers from distinct parts of clock neurons to engage different regions of behavior regulating circuitry. This strategy for expanding the connectome may be used for other neuropeptide dependent behaviors, such as feeding and pain perception.