bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metagenomic sequencing for rapid identification of Xylella fastidiosa from leaf samples
Authors: Roman-Reyna Veronica , Dupas Enora , Cesbron Sophie , Marchi Guido , Campigli Sara , Hansen Mary Ann , Bush Elizabeth , Prarat Melanie , Shiplett Katherine , Ivey Melanie L. Lewis , Pierzynski Joy , Miller Sally A. , Hand Francesca Peduto , Jacques Marie-Agnes , Jacobs Jonathan M. 
Published: May 2021

ABSTRACTXylella fastidiosa (Xf) is a globally distributed plant pathogenic bacterium. The primary control strategy for Xf diseases is eradicating infected plants; therefore, timely and accurate detection is necessary to prevent crop losses and further pathogen dispersal. Conventional Xf diagnostics primarily relies on quantitative PCR (qPCR) assays. However, these methods do not consider new or emerging variants due to pathogen genetic recombination and sensitivity limitations. We developed and tested a metagenomics pipeline using in-house short-read sequencing as a complementary approach for affordable, fast, and highly accurate Xf detection. We used metagenomics to identify Xf to strain level in single and mixed infected plant samples at concentrations as low as one picogram of bacterial DNA per gram of tissue. We also tested naturally infected samples from various plant species originating from Europe and the United States. We identified Xf subspecies in samples previously considered inconclusive with real-time PCR (Cq > 35). Overall, we showed the versatility of the pipeline by using different plant hosts and DNA extraction methods. Our pipeline provides taxonomic and functional information for Xf diagnostics without extensive knowledge of the disease. We hope this pipeline can be used for early detection of Xf and incorporated as a tool to inform disease management strategies.IMPORTANCEXylella fastidiosa (Xf) destructive outbreaks in Europe highlight this pathogen’s capacity to expand its host range and geographical distribution. The current disease diagnostic approaches are limited by a multiple-step process, biases to known sequences, and detection limits. We developed a low-cost, user-friendly metagenomic sequencing tool for Xf detection. In less than three days, we were able to identify Xf subspecies and strains in field-collected samples. Overall, our pipeline is a diagnostics tool that could be easily extended to other plant-pathogen interactions and implemented for emerging plant threat surveillance.
ABCDEF Bundle Implementation: The influence of access to bundle-enhancing supplies and equipment
Authors: Jeffery Alvin D. , Werthman Jennifer A. , Danesh Valerie , Dietrich Mary S. , Mion Lorraine C. , Boehm Leanne M. 
Published: May 2021

AbstractImportanceThe ABCDEF bundle is a guideline-recommended framework for implementing evidence-based practices in the Intensive Care Unit (ICU), but it is underutilized across the world.ObjectiveDescribe the physical environment factors (i.e., availability, accessibility) of bundle-enhancing items in units implementing the bundle and the influence of physical environment on bundle adherence.Design, Setting, and ParticipantsThis multicenter, exploratory, cross-sectional study used data from two ICU-based randomized controlled trials (RCTs) (NCT01211522 and NCT01739933) that measured daily bundle adherence. The study included 10 medical and surgical ICUs in 6 academic medical centers in the continental United States. Adults with qualifying respiratory failure and/or septic shock (e.g., mechanical ventilation, vasopressor use) were included in the RCTs. Unit- and patient-level data collection occurred between 2011 and 2016. We conducted hierarchical logistic regression models using Frequentist and Bayesian frameworks.ExposureThe ABCDE bundle (Awakening and Breathing trial Coordination, Delirium assessment/management, Early mobility) was recommended standard of care for RCT patients and adherence tracked daily.Measure(s)The primary outcome was adherence to the full bundle and the early mobility bundle component as identified from daily adherence documentation (n=751 patient observations). Unit-level measures included minimum and maximum distances to 25 bundle-enhancing items and the relationship to bundle adherence.ResultsIn all cases, mechanical ventilation was associated with decreased bundle adherence. Some of the models suggested the following variables were also influential: age (older associated with decreased adherence), unit size (larger associated with decreased adherence), and a standard walker (presence associated with increased adherence).Conclusions and RelevanceBoth unit- and patient-level barriers influenced full bundle and early mobility implementation. There is potential benefit of physical proximity to essential items for ABCDEF bundle and early mobility adherence. Future studies with larger sample sizes should explore how equipment location and availability influences practice.Key PointsQuestionDoes the physical environment, specifically the availability and accessibility of ABCDEF bundle-enhancing items, influence bundle adherence?FindingsIn this cross-sectional study in 10 units evaluating ABCDEF bundle adherence across 751 patient observations, units with access to a standard walker were significantly more likely to provide bundled care. Across all models, patients who were on the ventilator or older were significantly less likely to received bundled care.MeaningBoth unit- and patient-level factors influence ABCDEF bundle implementation and amenable targets for implementation strategy development.
Tyrosine Kinase Inhibitor Family of Drugs as Prospective Targeted Therapy for COVID-19 Based on In Silico And 3D-Human Vascular Lung Model Studies
Authors: Saxena Shalini , Meher Kranti , Rotella Madhuri , Vangala Subhramanyam , Chandran Satish , Malhotra Nikhil , Palakodeti Ratnakar , Voleti Sreedhara R , Saxena Uday 
Published: May 2021

AbstractCOVID-19 pandemic has ravaged the world and vaccines have been rapidly developed as preventive measures. But there is no target-based therapy which can be used if infection sets in. Remdesiver and dexamethasone were not designed to combat COVID-19 but are used clinically till better targeted therapies are available. Given this situation target based therapies that intervene in the disease pathway are urgently needed.Since COVID-19 genesis is driven by uncontrolled inflammation/thrombosis and protein kinases are critical in mounting this response, we explored if available tyrosine kinase inhibitors (TKI’s) can be used as intervention. We profiled four TKI’s namely; Lapatinib, Dasatinib, Pazopanib and Sitravatinib which inhibit tyrosine kinases but are completely distinct in their chemical structures.We demonstrate using in silico and an in vitro 3D-human vascular lung model which profiles anti-inflammatory and anti-thrombogenic properties that all four TKI’s are active in varying degrees. Our findings that chemically different TKI’s which share kinase inhibition as the common mechanism of action are active, strongly indicates that it’s a tyrosine kinase target-based activity and not off-target arbitrary effect. We propose that TKI’s, approved for human use and widely available, can be rapidly deployed as specific target-based therapy for COVID-19.
The compound of baicalein, wogonin, and oroxylin-A inhibiting EMT in A549 cell line via PI3K/AKT-TWIST1- glycolysis pathway
Authors: Cao Hui-Juan , Zhou Wei , Xian Xiao-Le , Sun Shu-Jun , Ding Pei-Jie , Tian Chun-Yu , Tian Fu-Ling , Jiang Chun-Hua , Fu Ting-Ting , Zhao Shu , Dai Jian-Ye 
Published: May 2021

AbstractNon-small cell lung cancer (NSCLC) is a worldwide disease with high morbidity and mortality, which is most derived from its metastasis. Some researches show that the epithelial-mesenchymal transition (EMT) process promotes lung cancer cells migration and invasion, leading to NSCLC metastasis. Total Flavonoid Aglycones Extract (TFAE) isolated from Scutellaria baicalensis was reported to inhibit tumor growth and induce apoptosis. In this study, we found that baicalein, wogonin, and oroxylin-A were the active compounds of TFAE. After reconstructing with these three compounds (baicalein (65.8%), wogonin (21.2%), and oroxylin-A (13.0%)), the reconstructed TFAE (reTFAE) present inhibitory effect on the EMT process of A549 cells. Then, bioinformatic technology was employed to elucidate the potential pharmacodynamic mechanism network of reTFAE. We identified the relationship between reTFAE and PI3K/Akt signaling pathways, with TWIST1 as the key protein. LY294002, the inhibitor of PI3K/Akt signaling pathway, and knock-down TWIST1 could significantly enhance the efficacy of reTFAE, with increasing expression of epithelial markers and decreasing expression of mesenchymal markers in A549 cells at the same time. Furthermore, stable isotope dimethyl-labeled proteomics technology was conducted to complement the follow-up mechanism that the EMT-inhibition process may be realized through glycolysis pathway. In conclusion, we claim that TWIST1-targeted flavonoids could provide a new strategy to inhibit EMT progress for the treatment of NSCLC.
Reversal of the adipostat control of torpor during migration in hummingbirds
Authors: Eberts Erich R. , Guglielmo Christopher G. , Welch Kenneth C. 
Published: May 2021

AbstractMany small endotherms use torpor to reduce metabolic rate and manage daily energy balance. However, the physiological “rules” that govern torpor use are unclear. We tracked torpor use and body composition in ruby-throated hummingbirds (Archilochus colubris), a long-distance migrant, throughout the summer using respirometry and quantitative magnetic resonance. During the mid-summer, birds entered torpor at consistently low fat stores (∼5% of body mass), and torpor duration was negatively related to evening fat load. Remarkably, this energy-emergency strategy was abandoned in the late summer when birds accumulated fat for migration. Migrating birds were more likely to enter torpor on nights when they had higher fat stores, and fat gain was positively correlated with the amount of torpor used. These findings demonstrate the versatility of torpor throughout the annual cycle and suggest a fundamental change in physiological feedback between adiposity and torpor during migration. Moreover, this study highlights the underappreciated importance of facultative heterothermy in migratory ecology.
Distinct Alterations in Cerebellar Connectivity with Substantia Nigra and Ventral Tegmental Area in Parkinson’s Disease
Authors: O’Shea Ian M. , Popal Haroon S. , Olson Ingrid R. , Murty Vishnu P. , Smith David V. 
Published: May 2021

AbstractIn Parkinson’s disease (PD), neurodegeneration of dopaminergic neurons occurs in the midbrain, specifically targeting the substantia nigra (SN), while leaving the ventral tegmental area (VTA) relatively spared in early phases of the disease. Although the SN and VTA are known to be functionally dissociable in healthy adults, it remains unclear how this dissociation is altered in PD. To examine this issue, we performed a whole-brain analysis to compare functional connectivity in PD to healthy adults using resting-state functional magnetic resonance imaging (rs-fMRI) data compiled from three independent datasets. Our analysis showed that across the sample, the SN had greater connectivity with the precuneus, anterior cingulate gyrus, and areas of the occipital cortex, partially replicating our previous work in healthy young adults. Notably, we also found that, in PD, VTA-right cerebellum connectivity was higher than SN-right cerebellum connectivity, whereas the opposite trend occurred in healthy controls. This double dissociation may reflect a compensatory role of the cerebellum in PD and could provide a potential target for future study and treatment.
Neuronal NADPH oxidase 2 in Parkinson’s disease pathogenesis
Authors: Keeney Matthew T. , Hoffman Eric K. , Farmer Kyle , Bodle Christopher R. , Fazzari Marco , Zharikov Alevtina , Castro Sandra L. , Kofler Julia K. , Cifuentes-Pagano Eugenia , Pagano Patrick J. , Burton Edward A. , Hastings Teresa G. , Greenamyre J. Timothy , Di Maio Roberto 
Published: May 2021

AbstractMitochondrial dysfunction and oxidative stress are strongly implicated in the pathogenesis of Parkinson’s disease (PD) and there is evidence that mitochondrially-generated superoxide can activate NADPH oxidase 2 (NOX2), which is a major enzymatic generator of superoxide. Although NOX2 has been examined in the context of PD, previous studies have focused on microglial function; the role of neuronal NOX2 in PD pathogenesis remains to be defined. Here we devised and validated a proximity ligation assay for NOX2 activity and demonstrated that in human PD and 2 models thereof, neuronal NOX2 is highly active in substantia nigra dopamine neurons. Further, NOX2 activity is responsible for accumulation, post-translational modification and oligomerization of α-synuclein as well as activation of leucine-rich repeat kinase 2 (LRRK2). Administration of a brain-penetrant, specific NOX2 inhibitor prevented NOX2 activation and its downstream effectsin vivoin a rat model of PD. We conclude that neuronal NOX2 is a major contributor to oxidative stress in PD, to α-synuclein pathology and to LRRK2 activation in idiopathic PD. In this context, NOX2 inhibitors hold potential as a disease-modifying therapy in PD.SummaryIn dopamine neuron, NADPH oxidase isoform 2 amplifies the oxidative stress-related pathogenic cascade in Parkinson’s disease
Insights into the secondary and tertiary structure of the Bovine Viral Diarrhea Virus Internal Ribosome Entry Site
Authors: Gosavi Devadatta , Wower Iwona , Beckmann Irene K. , Hofacker Ivo L. , Wower Jacek , Wolfinger Michael T. , Sztuba-Solinska Joanna 
Published: May 2021

ABSTRACTThe Internal Ribosome Entry Site (IRES) RNA of Bovine viral diarrhea virus (BVDV), an economically significant Pestivirus, is required for the cap-independent translation of viral genomic RNA. Thus, it is essential for viral replication and pathogenesis. We applied a combination of high-throughput biochemical RNA structure probing (SHAPE-MaP) and in silico modeling approaches to gain insight into the secondary and tertiary structures of BVDV IRES RNA. Our study demonstrated that BVDV IRES RNA forms in solution a modular architecture composed of three distinct structural domains (I-III). Two regions within domain III are engaged in tertiary interactions to form an H-type pseudoknot. Computational modeling of the pseudoknot motif provided a fine-grained picture of the tertiary structure and local arrangement of helices in the BVDV IRES. Furthermore, comparative genomics and consensus structure predictions revealed that the pseudoknot is evolutionarily conserved among many Pestivirus species. These studies provide detailed insight into the structural arrangement of BVDV IRES RNA H-type pseudoknot and encompassing motifs that likely contribute to the optimal functionality of viral cap-independent translation element.
Pseudomonas arenae sp. nov., Pseudomonas glycinis sp. nov. and Pseudomonas harudinis sp. nov., three novel bacterial species and plant endophytes
Authors: Seaton Sarah , Lemaire Jacqueline , Inderbitzin Patrik , Knight-Connoni Victoria , White James F. , Trujillo Martha E. 
Published: May 2021

ABSTRACTThree novel Pseudomonas species associated with healthy plants are described from the United States. They are Pseudomonas arenae sp. nov. from soybean in Missouri and Phragmites sp. in New Jersey; Pseudomonas glycinis sp. nov. from Vaccinium macrocarpon fruit in Massachusetts, groundwater in Tennessee and soybean in Indiana; and Pseudomonas harudinis sp. nov. from Phragmites sp. in New Jersey. No pathogenic strains are known for any of the novel species based on genome comparisons to assemblies in GenBank.
The conserved endocannabinoid anandamide modulates olfactory sensitivity to induce hedonic feeding in C. elegans
Authors: Levichev Anastasia , Faumont Serge , Berner Rachel Z. , Purcell Zhifeng , Lockery Shawn R. 
Published: May 2021

AbstractThe ability of cannabis to increase consumption of food has been known for centuries. In addition to producing hyperphagia, cannabinoids can amplify existing preferences for calorically dense, palatable food sources, a phenomenon called hedonic feeding. These effects result from the action of plant-derived cannabinoids on brain receptors where they mimic natural ligands called endocannabinoids. The high degree of conservation of cannabinoid signaling at the molecular level across the animal kingdom suggests hedonic feeding may also be widely conserved. Here we show that exposure of C. elegans to anandamide, an endocannabinoid common to nematodes and mammals, shifts both appetitive and consummatory responses toward nutritionally superior food, an effect analogous to hedonic feeding. We find that anandamide’s effect on feeding requires the C. elegans cannabinoid receptor NPR-19 but it can also be mediated by the human CB1 cannabinoid receptor, indicating functional conservation between the nematode and mammalian endocannabinoid systems for regulation of food preferences. Furthermore, the effect of anandamide in C. elegans is bidirectional, as it increases appetitive and consummatory responses to superior food but decreases these responses to inferior food. This bidirectionality is mirrored at the cellular level. Anandamide’s behavioral effects require the AWC chemosensory neurons, and anandamide renders these neurons more sensitive to superior food and less sensitive to inferior food. Our findings reveal a surprising degree of functional conservation in the effects of endocannabinoids on hedonic feeding across species and establish a new system in which to investigate the cellular and molecular basis of endocannabinoid system function in the regulation of food choice.
Population-level variation of enhancer expression identifies novel disease mechanisms in the human brain
Authors: Dong Pengfei , Hoffman Gabriel E. , Apontes Pasha , Bendl Jaroslav , Rahman Samir , Fernando Michael B. , Zeng Biao , Vicari James M. , Zhang Wen , Girdhar Kiran , Townsley Kayla G. , Misir Ruth ,   the CommonMind Consortium, Brennand Kristen J. , Haroutunian Vahram , Voloudakis Georgios , Fullard John F. , Roussos Panos 
Published: May 2021

AbstractIdentification of risk variants for neuropsychiatric diseases within enhancers underscores the importance of understanding the population-level variation of enhancers in the human brain. Besides regulating tissue- and cell-type-specific transcription of target genes, enhancers themselves can be transcribed. We expanded the catalog of known human brain transcribed enhancers by an order of magnitude by generating and jointly analyzing large-scale cell-type-specific transcriptome and regulome data. Examination of the transcriptome in 1,382 brain samples in two independent cohorts identified robust expression of transcribed enhancers. We explored gene-enhancer coordination and found that enhancer-linked genes are strongly implicated in neuropsychiatric disease. We identified significant expression quantitative trait loci (eQTL) for 25,958 enhancers which mediate 6.8% of schizophrenia heritability, mostly independent from standard gene eQTL. Inclusion of enhancer eQTL in transcriptome-wide association studies enhanced functional interpretation of disease loci. Overall, our study characterizes the enhancer-gene regulome and genetic mechanisms in the human cortex in both healthy and disease states.
Fast-spiking interneurons of the premotor cortex contribute to action planning
Authors: Giordano Nadia , Alia Claudia , Fruzzetti Lorenzo , Pasquini Maria , Mazzoni Alberto , Micera Silvestro , Fogassi Leonardo , Bonini Luca , Caleo Matteo 
Published: May 2021

SUMMARYPlanning and execution of voluntary movement depend on the contribution of distinct classes of neurons in primary motor and premotor areas. However, the specific functional role of GABAergic cells remains only partly understood. Here, electrophysiological and computational analyses are employed to compare directly the response properties of putative pyramidal (PNs) and fast-spiking, GABAergic neurons (FSNs) during licking and forelimb retraction in mice. Recordings from anterolateral motor cortex and rostral forelimb area, reveal that FSNs fire earlier and for a longer duration than PNs, with the exception of a subset of early-modulated PNs in deep layers. Computational analysis reveals that FSNs carry vastly more information than PNs about the onset of movement. While PNs differently modulate their discharge during distinct motor acts, most FSNs respond with a stereotyped increase in firing rate. Accordingly, the informational redundancy was greater among FSNs than PNs. These data suggest that a global rise of inhibition contributes to early action planning.
Archival influenza virus genomes from Europe reveal genomic and phenotypic variability during the 1918 pandemic
Authors: Patrono Livia Victoria , Vrancken Bram , Budt Matthias , Düx Ariane , Lequime Sebastian , Boral Sengül , Gilbert M. Thomas P. , Gogarten Jan F. , Hoffmann Luisa , Horst David , Merkel Kevin , Morens David , Prepoint Baptiste , Schlotterbeck Jasmin , Schuenemann Verena , Suchard Marc A. , Taubenberger Jeffery K. , Tenkhoff Luisa , Urban Christian , Widulin Navena , Winter Eduard , Worobey Michael , Leendertz Fabian H. , Schnalke Thomas , Wolff Thorsten , Lemey Philippe , Calvignac-Spencer Sébastien 
Published: May 2021

AbstractThe 1918 influenza pandemic was the deadliest respiratory pandemic of the 20th century and determined the genomic make-up of subsequent human influenza A viruses (IAV). Here, we analyze the first 1918 IAV genomes from Europe and from the first, milder wave of the pandemic. 1918 IAV genomic diversity is consistent with local transmission and frequent long-distance dispersal events and in vitro polymerase characterization suggests potential phenotypic variability. Comparison of first and second wave genomes shows variation at two sites in the nucleoprotein gene associated with resistance to host antiviral response, pointing at a possible adaptation of 1918 IAV to humans. Finally, phylogenetic estimates based on extended molecular clock modelling suggests a pure pandemic descent of seasonal H1N1 IAV as an alternative to the hypothesis of an intrasubtype reassortment origin.One Sentence SummaryMuch can be learned about past pandemics by uncovering their footprints in medical archives, which we here demonstrate for the 1918 flu pandemic.