bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ozone-induced changes in murine lung extracellular vesicle number and small RNA content
Authors: Smith Gregory J. , Tovar Adelaide , Kanke Matt , Sethupathy Praveen , Kelada Samir N. P. 
Published: June 2020

AbstractInhalation exposure to ozone (O3) causes adverse respiratory health effects that result from airway inflammation, a complex response mediated by changes to airway cellular transcriptional programs. These programs may be regulated in part by a subset of microRNAs transferred between cells (e.g. epithelial cells and macrophages) via extracellular vesicles (EV miRNA). To explore this, we exposed female C57BL/6J mice to filtered air (FA), 1, or 2 ppm O3by inhalation and collected bronchoalveolar lavage fluid (BALF) 21 hours later for markers of airway inflammation, EVs, and EV miRNA. Both concentrations of O3significantly increased markers of inflammation (neutrophils and total protein) and the number of EVs in the BALF. Using high-throughput small RNA sequencing, we identified several differentially expressed (DE) BALF EV miRNAs after 1 ppm (16 DE miRNAs) and 2 ppm (99 DE miRNAs) O3versus FA exposure. O3concentration response patterns in EV miRNA expression were apparent, particularly for the two most highly expressed (miR-2137 and miR-126-3p) and lowly expressed (miR-378-3p and miR-351-5p) miRNAs. Integrative analysis of EV miRNA expression and airway cellular mRNA expression identified EV miR-22-3p as a candidate regulator of transcriptomic responses to O3in airway macrophages. In contrast, we did not identify candidate miRNA regulators of mRNA expression data from conducting airways (predominantly composed of epithelial cells). In summary, our data show that O3exposure alters EV release and EV miRNA expression, suggesting that further investigation of EVs may provide insight into their effects on airway macrophage function and other mechanisms of O3-induced respiratory inflammation.
Phylogenomics of Ichneumonoidea (Hymenoptera) and implications for evolution of mode of parasitism and viral endogenization
Authors: Sharanowski Barbara J. , Ridenbaugh Ryan D. , Piekarski Patrick K. , Broad Gavin R. , Burke Gaelen R. , Deans Andrew R. , Lemmon Alan R. , Lemmon Emily C. Moriarty , Diehl Gloria J. , Whitfield James B. , Hines Heather M. 
Published: June 2020

AbstractIchneumonoidea is one of the most diverse lineages of animals on the planet with more than 48,000 described species and many more undescribed. Parasitoid wasps of this superfamily are beneficial insects that attack and kill other arthropods and are important for understanding diversification and the evolution of life history strategies related to parasitoidism. Further, some lineages of parasitoids within Ichneumonoidea have acquired endogenous virus elements (EVEs) that are permanently a part of the wasp’s genome and benefit the wasp through host immune disruption and behavioral control. Unfortunately, understanding the evolution of viral acquisition, parasitism strategies, diversification, and host immune disruption mechanisms, is deeply limited by the lack of a robust phylogenetic framework for Ichneumonoidea. Here we design probes targeting 541 genes across 91 taxa to test phylogenetic relationships, the evolution of parasitoid strategies, and the utility of probes to capture polydnavirus genes across a diverse array of taxa. Phylogenetic relationships among Ichneumonoidea were largely well resolved with most higher-level relationships maximally supported. We noted codon use biases between the outgroups, Braconidae, and Ichneumonidae and within Pimplinae, which were largely solved through analyses of amino acids rather than nucleotide data. These biases may impact phylogenetic reconstruction and caution for outgroup selection is recommended. Ancestral state reconstructions were variable for Braconidae across analyses, but consistent for reconstruction of idiobiosis/koinobiosis in Ichneumonidae. The data suggest many transitions between parasitoid life history traits across the whole superfamily. The two subfamilies within Ichneumonidae that have polydnaviruses are supported as distantly related, providing strong evidence for two independent acquisitions of ichnoviruses. Polydnavirus capture using our designed probes was only partially successful and suggests that more targeted approaches would be needed for this strategy to be effective for surveying taxa for these viral genes. In total, these data provide a robust framework for the evolution of Ichneumonoidea.
Comparative phylogeography reveals how a barrier filters and structures taxa in North American warm deserts
Authors: Provost Kaiya L. , Myers Edward A. , Smith Brian Tilston 
Published: June 2020

AbstractThe study of biogeographic barriers have been instrumental in understanding the evolution and distribution of taxa. Now with the increased availability of empirical datasets, it is possible to infer emergent patterns from communities by synthesizing how barriers filter and structure populations across species. We assemble phylogeographic data for a barrier and perform spatially-explicit simulations to quantify temporal and spatial patterns of divergence, the influence of species traits on these patterns, and understand the statistical power of differentiating alternative diversification modes. We incorporate published datasets to examine taxa around the Cochise Filter Barrier, separating the Sonoran and Chihuahuan deserts of North America, to synthesize phylogeographic structuring across the community with respect to organismal functional traits. We then use a simulation and machine learning pipeline to assess the power of phylogeographic model selection. Taxa distributed across the Cochise Filter Barrier show heterogeneous responses to the barrier in levels of gene flow, phylogeographic structure, divergence timing, barrier width, and divergence mechanism. These responses vary concordantly with locomotor and thermoregulatory traits. Many taxa show a Pleistocene population genetic break, often with introgression after divergence. Allopatric isolation and isolation-by-environment are the primary mechanisms purported to structure taxa. Simulations reveal that in spatially-explicit isolation-with-migration models across the barrier, age of divergence, presence of gene flow, and presence of isolation-by-distance can confound the interpretation of evolutionary history and model selection by producing easily-confusable results. By synthesizing phylogeographic data for the Cochise Filter Barrier we show a pattern where barriers interact with species traits to differentiate taxa in communities over millions of years. Identifying the modes of differentiation across the barriers for these taxa remains challenging because commonly invoked demographic models may not be identifiable across a range of likely parameter space.
A hand-off of DNA between archaeal polymerases allows high-fidelity replication to resume at a discrete intermediate three bases past 8-oxoguanine
Authors: Cranford Matthew T. , Kaszubowski Joseph D. , Trakselis Michael A. 
Published: June 2020

AbstractDuring DNA replication, the presence of 8-oxoguanine (8-oxoG) lesions in the template strand cause the high-fidelity (HiFi) DNA polymerase (Pol) to stall. An early response to 8-oxoG lesions involves ‘on-the-fly’ translesion synthesis (TLS), in which a specialized TLS Pol is recruited and replaces the stalled HiFi Pol for bypass of the lesion. The length of TLS must be long enough for effective bypass, but it must also be regulated to minimize replication errors by the TLS Pol. The exact position where the TLS Pol ends and the HiFi Pol resumes (i.e. the length of the TLS patch) has not been described. We use steady-state and pre-steady-state kinetic assays to characterize lesion bypass intermediates formed by different archaeal polymerase holoenzyme complexes that include PCNA123 and RFC. After bypass of 8-oxoG by TLS PolY, products accumulate at the template position three base pairs beyond the lesion. PolY is catalytically poor for subsequent extension from this +3 position beyond 8-oxoG, but this inefficiency is overcome by rapid extension of HiFi PolB1. The reciprocation of Pol activities at this intermediate indicates a defined position where TLS Pol extension is limited and where the DNA substrate is handed back to the HiFi Pol after bypass of 8-oxoG.
The mechanisms behind perivascular fluid flow
Authors: Daversin-Catty Cécile , Vinje Vegard , Mardal Kent-André , Rognes Marie E. 
Published: June 2020

Flow of cerebrospinal fluid (CSF) in perivascular spaces (PVS) is one of the key concepts involved in theories concerning clearance from the brain. Experimental studies have demonstrated both net and oscillatory movement of microspheres in PVS (Mestre et al. (2018), Bedussi et al. (2018)). The oscillatory particle movement has a clear cardiac component, while the mechanisms involved in net movement remain disputed. Using computational fluid dynamics, we computed the CSF velocity and pressure in a PVS surrounding a cerebral artery subject to different forces, representing arterial wall expansion, systemic CSF pressure changes and rigid motions of the artery. The arterial wall expansion generated velocity amplitudes of 60–260µm/s, which is in the upper range of previously observed values. In the absence of a static pressure gradient, predicted net flow velocities were small (<0.5µm/s), though reaching up to 7µm/s for non-physiological PVS lengths. In realistic geometries, a static systemic pressure increase of physiologically plausible magnitude was sufficient to induce net flow velocities of 20–30µm/s. Moreover, rigid motions of the artery added to the complexity of flow patterns in the PVS. Our study demonstrates that the combination of arterial wall expansion, rigid motions and a static CSF pressure gradient generates net and oscillatory PVS flow, quantitatively comparable with experimental findings. The static CSF pressure gradient required for net flow is small, suggesting that its origin is yet to be determined.Significance StatementCerebrospinal fluid flow along perivascular spaces is hypothesized to be instrumental for clearance of metabolic waste from the brain, such as e.g. clearance of amyloid-beta, a protein known to accumulate as plaque within the brain in Alzheimer’s patients. Arterial pulsations have been proposed as the main driving mechanism for perivascular fluid flow, but it is unclear whether this mechanism alone is sufficient. Our results show that arterial pulsations drive oscillatory movement in perivascular spaces, but also indicate that a pressure gradient is required for net flow. However, the required pressure gradient is relatively small, thus suggesting that its origins can be associated with physiological processes within the brain and/or experimental procedures.
Local and global analysis of macromolecular Atomic Displacement Parameters
Authors: Masmaliyeva Rafiqa C , Babai Kaveh H , Murshudov Garib N 
Published: June 2020

AbstractThis paper describes the global and local analyses of Atomic Displacement Parameters (ADP) of macromolecules solved and refined using X-ray crystallography method. It is shown that the distribution of ADPs follows the (mixture of) Shifted Inverse Gamma distribution(s). The parameters of the mixture of SIGDs are estimated using Expectation/Maximisation methods. In addition, a method for resolution and individual ADP dependent local analysis of neighbouring atoms has been designed. This method facilitates the detection of the mismodelled atoms and indicates potential identity of heavy metal atoms. It also helps in detecting of disordered and/or wrongly modelled ligands. Both global and local analyses can be used to detect errors in atomic structures thus helping in (re)building, refinement and validation of macromolecular structures. It can also serve as an additional validation tool during data deposition to the PDB.SynopsisMacromolecular atomic B value distributions have been modelled using a mixture of Shifted Inverse Gamma Distribution. Also, B value and resolution dependent local ADP differences have been applied for validation of heavy atoms and ligands.
Y disruption, autosomal hypomethylation and poor male lung cancer survival
Authors: Willis-Owen Saffron A.G. , Sabugo Clara Domingo , Starren Elizabeth , Liang Liming , Freidin Maxim B. , Arseneault Madeleine , Zhang Youming , Lu Shir Kiong , Popat Sanjay , Lim Eric , Nicholson Andrew G. , Riazalhosseini Yasser , Lathrop Mark , Cookson William O.C. , Moffatt Miriam F. 
Published: June 2020

SummaryLung cancer is the most frequent cause of cancer death worldwide1. It is male predominant and for reasons that are unknown also associated with significantly worse outcomes in men2. Here we compared gene co-expression networks in affected and unaffected pulmonary tissue derived from 126 patients with Stage IA–IV lung cancer. We observed marked degradation of a sex-associated gene co-expression network in tumour tissue. The disturbance was linked to fractional loss of the Y chromosome and was detected in 28% of male tumours in the discovery dataset and 27% of male tumours in a 123 sample replication dataset. Depression of Y chromosome expression was accompanied by extensive autosomal DNA hypomethylation. The male specific H3K4 demethylase, KDM5D, was identified as an apex hub within this co-expression network. Male patients exhibiting relative tumour KDM5D deficiency had an increased risk of death in the discovery dataset (Hazard Ratio [HR] 3.80, 95% CI 1.40 – 10.3, P=0.009) and in an independent sample of 1,100 male lung tumours (HR 1.67, 95% CI 1.4-2.0, P=1.2⨯10−10). Our findings identify tumour-specific weakening of male-specific expression, in particular deficiency of KDM5D, as a common replicable prognostic marker and credible mechanism underlying sex disparity in cancer.
The Endothelial Dysfunction and Pyroptosis Might Drive the SARS-CoV-2 Lung Injury to the Systemic Immunothrombosis
Authors: Nagashima Seigo , Mendes Monalisa C. , Martins Ana Paula C. , Borges Nicolas H. , Godoy Thiago M. , dos Santos Miggiolaro Anna Flavia Ribeiro , Dezidério Felipe S. , de Noronha Lucia , Machado-Souza Cleber 
Published: June 2020

ABSTRACTObjectiveEndothelial cells that are close to the alveolar-capillary exchange membranes can be activated by SARS-CoV-2 infection leading to cytokine release and macrophage activation syndrome. This could trigger endothelial dysfunction, pyroptosis, and immunothrombosis, which are the vascular changes commonly referred to as COVID-19 endotheliopathy. Thus, this study aimed to identify tissue biomarkers associated with endothelial activation/dysfunction and the pyroptosis pathway in the lung and myocardial samples of COVID-19 patients and to compare them to pandemic Influenza A virus H1N1 subtype – 2009 and Control cases.Approach and ResultsPost-mortem lung (COVID-19 group=6 cases; H1N1 group=10 cases, and Control group=11 cases) and myocardial samples (COVID-19=2 cases and control=1 case) were analyzed using immunohistochemistry and the following monoclonal primary antibodies: anti-CD163, anti-interleukin-6 (IL-6), anti-tumor necrosis factor-alpha (TNF-alpha), anti-intercellular adhesion molecule-1 (ICAM-1), and anti-caspase-1. From the result, IL-6, TNF-alpha, ICAM-1, and caspase-1 showed higher tissue expression in the COVID-19 group than in the H1N1 and control groups.ConclusionOur results demonstrated the presence of endotheliopathy and suggest the participation of the pyroptosis pathway in both the pulmonary and myocardial samples. These conditions might lead to systemic immunothrombotic events that could impair the efforts of clinical staff to avoid fatal outcomes. One of the goals of health professionals should be to identify the high-risk of immunothrombosis patients early to block endotheliopathy and its consequences.
FAR AWAY FROM HERD IMMUNITY TO SARS-CoV-2: results from a survey in healthy blood donors in South Eastern Italy
Authors: Fiore Josè Ramòn , Centra Michele , De Carlo Armando , Granato Tommaso , Rosa Annamaria , Sarno Michelina , De Feo Lucia , Di Stefano Mariantonietta , D’Errico Maria L. , Caputo Sergio Lo , De Nittis Rosella , Arena Fabio , Corso Gaetano , Margaglione Maurizio , Santantonio Teresa Antonia 
Published: June 2020

ABSTRACTHere we present results from a survey on anti-SARS-CoV-2 seroprevalence in healthy blood donors from a low incidence COVID-19 area (Apulia region, South Eastern Italy).Among 904 subjects tested, only in 9 cases (0.99%) antibodies against SARS-CoV-2 were demonstrated. All the 9 seropositive patients were negative for the research of viral RNA by RT-PCR in nasopharyngeal swab.These data, along with those recently reported from other countries, clearly show that we are very far from herd immunity and that the containment measures are at the moment the only realistic instrument we have to slow the spread of the pandemic.
UV-C Tower for point-of-care decontamination of filtering facepiece respirators
Authors: Kayani Badar J. , Weaver Davis T. , Gopalakrishnan Vishvaan , King Eshan S. , Dolson Emily , Krishnan Nikhil , Pelesko Julia , Scott Michael J. , Hitomi Masahiro , Cadnum Jennifer L. , Li Daniel F. , Donskey Curtis J. , Scott Jacob G. , Charnas Ian 
Published: June 2020

ABSTRACTFiltering facepiece respirators (FFR) are critical for protecting essential personnel and limiting the spread of disease. Due to the current COVID-19 pandemic, FFR supplies are dwindling in many health systems, necessitating re-use of potentially contaminated FFR. Multiple decontamination solutions have been developed to meet this pressing need, including systems designed for bulk decontamination of FFR using vaprous hydrogen peroxide or UV-C radiation. However, the large scale on which these devices operate may not be logistically practical for small or rural health care settings or for ad hoc use at points-of-care. Here, we present the Synchronous UV Decontamination System (SUDS), a novel device for rapidly deployable, point-of-care decontamination using UV-C germicidal irradiation. We designed a compact, easy-to-use device capable of delivering over 2 J· cm−2 of UV-C radiation in one minute. We experimentally tested SUDS’ microbicidal capacity and found that it eliminates near all virus from the surface of tested FFRs, with less efficacy against pathogens embedded in the inner layers of the masks. This short decontamination time should enable care-providers to incorporate decontamination of FFR into a normal donning and doffing routine following patient encounters.
Toward patient-centered tuberculosis preventive treatment: preferences for regimens and formulations in Lima, Peru
Authors: Yuen Courtney M. , Millones Ana K. , Galea Jerome T. , Puma Daniela , Jimenez Judith , Lecca Leonid , Becerra Mercedes C. , Keshavjee Salmaan 
Published: June 2020

ABSTRACTBackgroundTo ensure patient-centered TB preventive treatment, it is important to consider factors that make it easier for patients to complete treatment. However, there is little published literature about patient preferences for different preventive treatment regimen options, particularly from countries with high tuberculosis burdens.MethodsWe conducted a qualitative research study using a framework analysis approach to understand preventive treatment preferences among household contacts. We conducted three focus group discussions with 16 members of families affected by TB in Lima, Peru. Participants were asked to vote for preferred preventive treatment regimens and discuss the reasons behind their choices. Coding followed a deductive approach based on prior research, with data-driven codes added.ResultsIn total, 7 (44%) participants voted for 3 months isoniazid and rifapentine, 4 (25%) chose 3 months isoniazid and rifampicin, 3 (19%) chose 4 months rifampicin, and 2 (13%) chose 6 months isoniazid. Preferences for shorter regimens over 6 months of isoniazid were driven by concerns over “getting tired” or “getting bored” of taking medications, the difficulty of remembering to take medications, side effects, and interference with daily life. For some, weekly dosing was perceived as being easier to remember and less disruptive, leading to a preference for 3 months isoniazid and rifapentine, which is dosed weekly. However, among caregivers, having a child-friendly formulation was more important than regimen duration. Caregivers reported difficulty in administering pills to children, and preferred treatments available as syrup or dispersible formulations.ConclusionsThere is demand for shorter regimens and child-friendly formulations for preventive treatment in a high-burden setting. Individual preferences differ, suggesting that patient-centered care would best be supported by having multiple shorter regimens available.
Systematic analysis of REBASE identifies numerous Type I restriction-modification systems that contain duplicated, variablehsdSspecificity genes that randomly switch methyltransferase specificity by recombination
Authors: Atack John M. , Guo Chengying , Litfin Thomas , Yang Long , Blackall Patrick J. , Zhou Yaoqi , Jennings Michael P. 
Published: June 2020

AbstractN6-adenine DNA methyltransferases associated with some Type I and Type III restriction-modification (R-M) systems are able to randomly switch expression by variation in the length of locus-encoded simple sequence repeats (SSRs). SSR tract-length variation causes ON/OFF switching of methyltransferase expression, resulting in genome-wide methylation differences, and global changes in gene expression. These epigenetic regulatory systems are called phasevarions, phase-variable regulons, and are widespread in bacteria. A distinct switching system has also been described in Type I R-M systems, based on recombination-driven changes inhsdSgenes, which dictate the DNA target site. In order to determine the prevalence of recombination-driven phasevarions, we generated a program called RecombinationRepeatSearch to interrogate REBASE and identify the presence and number of inverted repeats ofhsdSdownstream of Type I R-M loci. We report that 5.9% of Type I R-M systems have duplicated variablehsdSgenes containing inverted repeats capable of phase-variation. We report the presence of these systems in the major pathogensEnterococcus faecalisandListeria monocytogenes, which will have important implications for pathogenesis and vaccine development. These data suggest that in addition to SSR-driven phasevarions, many bacteria have independently evolved phase-variable Type I R-M systems via recombination between multiple, variablehsdSgenes.ImportanceMany bacterial species contain DNA methyltransferases that have random on/off switching of expression. These systems called phasevarions (phase-variable regulons) control the expression of multiple genes by global methylation changes. In every previously characterised phasevarion, genes involved in pathobiology, antibiotic resistance, and potential vaccine candidates are randomly varied in their expression, commensurate with methyltransferase switching. A systematic study to determine the extent of phasevarions controlled by invertible Type I R-M systems has never before been performed. Understanding how bacteria regulate genes is key to the study of physiology, virulence, and vaccine development; therefore it is critical to identify and characterize phase-variable methyltransferases controlling phasevarions.