bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid evolution drives the rise and fall of carbapenem resistance during an acutePseudomonas aeruginosainfection
Authors: Wheatley Rachel , Caballero Julio Diaz , Kapel Natalia , Quinn Angus , del Barrio-Tofiño Ester , López-Causapé Carla , Hedge Jessica , Torrens Gabriel , Van der Schalk Thomas , Britto Xavier Basil , Fernández-Cuenca Felipe , Arenzana Angel , Recanatini Claudia , Timbermont Leen , Sifakis Frangiscos , Ruzin Alexey , Ali Omar , Lammens Christine , Goossens Herman , Kluytmans Jan , Kumar-Singh Samir , Oliver Antonio , Malhotra-Kumar Surbhi , MacLean Craig 
Published: August 2020

AbstractIt is well established that antibiotic treatment selects for resistance in pathogenic bacteria. However, the evolutionary responses of pathogen populations to antibiotic treatment during infections remain poorly resolved, especially in acute infections. Here we map the evolutionary responses to treatment in high definition through genomic and phenotypic characterization of >100 isolates from a patient withP. aeruginosapneumonia. Antibiotic therapy (meropenem, colistin) caused a rapid crash of theP. aeruginosapopulation in the lung, but this decline was followed by the spread of meropenem resistance mutations that restrict antibiotic uptake (oprD) or modify LPS biosynthesis (wbpM). Low fitness strains with high-level meropenem resistance (oprD) were then replaced by high fitness strains with ‘anti-resistance’ mutations in the MexAB-OprM efflux pump, causing a rapid decline in resistance to both meropenem and a collateral loss of resistance to a broad spectrum of antibiotics. In contrast, we did not observe any evolutionary responses to antibiotic treatment in the intestinal population ofP. aeruginosa. Carbapenem antibiotics are key to the treatment of infections caused by Gram negative pathogens, and our work highlights the ability of natural selection to drive both the rapid rise and fall of carbapenem resistance during acute infections.
Modeling Risks and Mitigation Options for the Chronic Wasting Disease (CWD) in Scandinavia
Authors: Franklin Oskar , Moltchanova Elena , Krasovskiy Andrey , Kraxner Florian 
Published: August 2020

AbstractChronic wasting disease (CWD) is a contagious neural prion-disease affecting deer populations in North America with severe ecological and societal consequences. CWD is fatal and infectious prions spread and remain in the environment for many years even without animals present. The recent appearance of CWD in reindeers in Norway called for a drastic culling operation to prevent further spreading of the disease. This appears to have stopped the spreading of CWD among reindeers, but due to the persistence of CWD prions in the environment a reappearance of new cases among reindeer or other species in the future cannot be excluded. To evaluate the risks and the effectiveness of alternative management (monitoring and culling) options, we developed a model of CWD dynamics and management. The model includes stochastic population and spatial dynamics of the four relevant deer species in northern Sweden and Norway: reindeer (Rangifer tarandus), roe deer (Capreolus capreolus), red deer (Cervus elaphus) and moose (Alces alces). Transmission of CWD is modelled via direct contacts and via the environment. The model was parameterized and calibrated based on CWD studies from USA, data from the Norwegian CWD cases, and local deer population and vegetation data. The results indicate that without management, a CWD epidemic can be initiated by a single infected reindeer and would spread to other deer species. It would lead to dramatic population declines of reindeer and red deer and would also reduce the populations of roe deer and moose. The disease prevalence would stabilise at a about 50% after 50 years, as observed in some areas in the USA. A management strategy to cull only visibly sick animals, even with very efficient detection, cannot prevent a catastrophic development but merely slow the outbreak. To prevent an outbreak and the establishment of CWD it is necessary to cull all individuals, not only visibly sick ones, of an affected species in a relatively large area (30×30 km in our model) once a case is detected. Further, to prevent a slow buildup of CWD in the environment and eliminate the risk of outbreaks in the future it is necessary to expand this area of culling even further. Although the model has not yet been thoroughly validated due to scarcity of data, the results suggest that the drastic culling done in Norway was appropriate and necessary to prevent establishment of CWD and that further monitoring and potential culling is required to prevent outbreaks in the future.
SPARC regulation of PMN clearance protects from pristane induced lupus and rheumatoid arthritis
Authors: Sangaletti Sabina , Botti Laura , Gulino Alessandro , Lecis Daniele , Bassani Barbara , Portararo Paola , Milani Matteo , De Cecco Loris , Dugo Matteo , Tripodo Claudio , Colombo Mario P. 
Published: August 2020

AbstractOne step along the pathogenesis of Systemic lupus erythematosus (SLE) is associated with polymorphonuclear leukocyte (PMN) death and their ineffective removal by M2-macrophages. The secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein with unexpected immunosuppressive function in M2-macrophages and myeloid cells. To investigate the role of SPARC in autoimmunity, we adopted a pristane–induced model of lupus in mice, which recapitulates clinical manifestations of human SLE.Sparc-/-mice developed earlier and more severe renal disease, lung and liver parenchymal damage than the WT counterpart. Most prominently,Sparc-/-mice had anticipated and severe occurrence of arthritis. An intermediate phenotype was obtained inSparc+/-hemizygous mice, a result that suggestsSparcgene-dosage as relevant in autoimmune-related events. Mechanistically, a defectiveSparcexpression in PMN blocks their clearance by macrophages, through a defective delivery of eat-me and don’t eat-me signals.Sparc-/-PMN that escape macrophage scavenging becomes a source of autoantigens for dendritic cell (DC) presentation and a direct stimulus for IL-17 expression in γδ-T-cells. Gene profile analysis of synovial biopsies of knees affected by SLE-associated arthritis showed an inverse correlation between SPARC and key autoimmune genes. These results point to SPARC down-regulation as a key event characterizing SLE and associated rheumatoid arthritis pathogenesis.
Heterotrophic flagellates and centrohelid heliozoans from marine waters of Curacao, the Netherlands Antilles
Authors: Prokina Kristina I. , Keeling Patrick J. , Tikhonenkov Denis V. 
Published: August 2020

AbstractRecent progress in understanding the early evolution of eukaryotes was tied to morphological identification of flagellates and heliozoans in the natural samples, isolation of their cultures and genomic and ultrastructural investigations. These protists are the smallest and least studied microbial eukaryotes but play an important role in functioning of microbial food webs. Using light and electron microscopy, we have studied the diversity of heterotrophic flagellates and centrohelid heliozoans from marine waters of Curacao (The Netherlands Antilles), and provide micrographs and morphological descriptions of observed species. Among 86 flagellates and 3 centrohelids encountered in this survey, five heterotrophic flagellates and one Centrohelid heliozoan were not identified even to the genus. Some flagellate protists have a unique morphology, and may represent undescribed lineages of eukaryotes of high taxonomic rank. The vast majority (89%) of identified flagellates are characterized by wide geographical distribution and had been reported previously from all hemispheres and various climatic regions. More than half of the species were previously observed not only from marine, but also from freshwater habitats. The parameters of the species accumulation curve indicate that our species list obtained for the Curacao study sites is far from complete, and each new sample should yield new species.
Identification of limb-specificLmx1bauto-regulatory modules with Nail-Patella Syndrome pathogenicity
Authors: Haro Endika , Petit Florence , Pira Charmaine U. , Spady Conor D. , Ivey Lauren A. , Gray Austin L. , Escande Fabienne , Jourdain Anne-Sophie , Nguyen Andy , Fellmann Florence , Good Jean-Marc , Francannet Christine , Manouvrier-Hanu Sylvie , Ros Marian A. , Oberg Kerby C. 
Published: August 2020

AbstractLMX1Bhaploinsufficiency causes Nail-patella syndrome (NPS; MIM 161200), characterized by nail dysplasia, absent/hypoplastic patellae, chronic kidney disease, and glaucoma. Accordingly, in miceLmx1bhas been shown to play crucial roles in the development of the limb, kidney and eye. Although one functional allele of murineLmx1bappears adequate for development,Lmx1bnull mice display ventral-ventral distal limbs with abnormal kidney, eye and cerebellar development, more disruptive, but fully concordant with NPS. Interestingly, inLmx1bfunctional knockouts (KOs),Lmx1btranscription in the limb is decreased nearly 6-fold indicating autoregulation. Herein, we report on two conservedLmx1b-associatedcis-regulatorymodules (LARM1andLARM2)that are bound by Lmx1b, amplifyLmx1bexpression in the limb and are necessary for Lmx1b-mediated limb dorsalization. Remarkably, we also report on two NPS patient families with normalLMX1Bcoding sequence, but loss-of-function variations in theLARM1/2region, stressing the role of regulatory modules in disease pathogenesis.
Genome-wide analysis of DNA replication and DNA double strand breaks by TrAEL-seq
Authors: Kara Neesha , Krueger Felix , Rugg-Gunn Peter , Houseley Jonathan 
Published: August 2020

AbstractUnderstanding the distribution of sites at which replication forks stall, and the ensuing fork processing events, requires genome-wide methods sensitive to both changes in replication fork structure and the formation of recombinogenic DNA ends. Here we describeTransferase-ActivatedEndLigationsequencing (TrAEL-seq), a method that captures single stranded DNA 3’ ends genome-wide and with base pair resolution. TrAEL-seq labels DNA breaks, and profiles both stalled and processive replication forks in yeast and mammalian cells. Replication forks stalling at defined barriers and expressed genes are detected by TrAEL-seq with exceptional signal-to-noise, most likely through labelling of DNA 3’ ends exposed during fork reversal. TrAEL-seq also labels unperturbed processive replication forks to yield maps of replication fork direction similar to those obtained by Okazaki fragment sequencing, however TrAEL-seq is performed on asynchronous populations of wild-type cells without incorporation of labels, cell sorting, or biochemical purification of replication intermediates, rendering TrAEL-seq simpler and more widely applicable than existing replication fork direction profiling methods. The specificity of TrAEL-seq for DNA 3’ ends also allows accurate detection of double strand break sites after the initiation of DNA end resection, which we demonstrate by genome-wide mapping of meiotic double strand break hotspots in admc1Δ mutant. Overall, TrAEL-seq provides a flexible and robust methodology with high sensitivity and resolution for studying DNA replication and repair, which will be of significant use in determining mechanisms of genome instability.
Gut microbial communities associated with phenotypically divergent populations of the striped stem borerChilo suppressalis
Authors: Zhong Haiying , Chen Jianming , Zhang Juefeng , Li Fang 
Published: August 2020

AbstractChilo suppressalisis a serious stem borer of rice and water-oat, however, little is known about the effect of diet and gut compartments on the gut microbial communities of this species. We analyzed the microbial communities in phenotypically divergent populations ofC. suppressalis. In original and cross-rearing populations, the most dominant phyla were Proteobacteria (16.0% to 96.4%) and Firmicutes (2.3% to 78.9%); the most abundant family were Enterobacteriaceae (8.0% to 78%), followed by Enterococcaceae (1.7% to 64.2%) and Halomonadaceae (0.3% to 69.8%). The genera distribution showed great differences due to diet types and gut compartments. The fewest microbial species were shared by original populations, whereas the highest bacteria diversity was found for midgut of rice population feeding on water-oat. The bacterial communities in the midgut were more diverse than those in the hindgut. A comparison among phenotypically divergent populations ofC. suppressalisshows that gut microbial communities vary with diet types and gut compartment.
A comparison of non-magnetic and magnetic beads for measuring IgG antibodies againstP. vivaxantigens in a multiplexed bead-based assay using Luminex®technology (Bio-Plex®200 or MAGPIX®)
Authors: Mazhari Ramin , Brewster Jessica , Fong Rich , Bourke Caitlin , Liu Zoe SJ , Takashima Eizo , Tsuboi Takafumi , Tham Wai-Hong , Harbers Matthias , Chitnis Chetan , Healer Julie , Ome-Kaius Maria , Sattabongkot Jetsumon , Kazura James , Robinson Leanne J. , King Christopher , Mueller Ivo , Longley Rhea J. 
Published: August 2020

AbstractMultiplexed bead-based assays that use Luminex xMAP®technology have become popular for measuring antibodies against proteins of interest in many fields, including malaria and more recently SARS-CoV-2/COVID-19. There are currently two formats that are widely used: non-magnetic beads or magnetic beads. Data is lacking regarding the comparability of results obtained using these two types of beads, and for assays run on different instruments. Whilst non-magnetic beads can only be run on flow-based instruments (such as the Luminex®100/200™ or Bio-Plex®200), magnetic beads can be run on both these and the newer MAGPIX®instruments. In this study we utilized a panel of purified recombinantPlasmodium vivaxproteins and samples from malaria-endemic areas to measureP. vivax-specific IgG responses using different combinations of beads and instruments. We directly compared: i) non-magnetic versus magnetic beads run on a Bio-Plex®200, ii) magnetic beads run on the Bio-Plex®200 versus MAGPIX®and iii) non-magnetic beads run on a Bio-Plex®200 versus magnetic beads run on the MAGPIX®. We also performed an external validation of our optimized assay. We observed that IgG antibody responses, measured against our panel ofP. vivaxproteins, were strongly correlated in all three of our comparisons, however higher amounts of protein were required for coupling to magnetic beads. Our external validation indicated that results generated in different laboratories using the same coupled beads are also highly comparable, particularly if a reference standard curve is used.
CoRhythMo: A Computational Framework for Modeling Biobehavioral Rhythms from Mobile and Wearable Data Streams
Authors: Yan Runze , Liu Xinwen , Dutcher Janine M , Tumminia Michael J , Villalba Daniella , Cohen Sheldon , Creswell David , Creswell Kasey , Mankoff Jennifer , Dey Anind K , Doryab Afsaneh 
Published: August 2020

AbstractThis paper presents CoRhythMo, the first computational framework for modeling biobehavioral rhythms - the repeating cycles of physiological, psychological, social, and environmental events - from mobile and wearable data streams. The framework incorporates four main components: mobile data processing, rhythm discovery, rhythm modeling, and machine learning. We use a dataset of smartphone and Fitbit data collected from 138 college students over a semester to evaluate the framework’s ability to 1) model biobehavioral rhythms of students, 2) measure the stability of their rhythms over the course of the semester, 3) model differences between rhythms of students with different health status, and 4) predict the mental health status in students using the model of their biobehavioral rhythms. Our evaluation provides evidence for the feasibility of using CoRhythMo for modeling and discovering human rhythms and using them to assess and predict different life and health outcomes.
Scanned optogenetic control of mammalian somatosensory input to map input-specific behavioral outputs
Authors: Schorscher-Petcu Ara , Takács Flóra , Browne Liam E. 
Published: August 2020

AbstractSomatosensory stimuli guide and shape behavior, from immediate protective reflexes to longer-term learning and high-order processes related to pain and touch. However, somatosensory inputs are challenging to control in awake mammals due to the diversity and nature of contact stimuli. Application of cutaneous stimuli is currently limited to relatively imprecise methods as well as subjective behavioral measures. The strategy we present here overcomes these difficulties by achieving spatiotemporally precise, remote and dynamic optogenetic stimulation of skin by projecting light to a small defined area in freely-behaving mice. We mapped behavioral responses to specific nociceptive inputs and revealed a sparse code for stimulus intensity: using the first action potential, the number of activated nociceptors governs the timing and magnitude of rapid protective pain-related behavior. The strategy can be used to define specific behavioral repertoires, examine the timing and nature of reflexes, and dissect sensory, motor, cognitive and motivational processes guiding behavior.
The record of Deinotheriidae from the Miocene of the Swiss Jura Mountains (Jura Canton, Switzerland)
Authors: Gagliardi Fanny , Maridet Olivier , Becker Damien 
Published: August 2020

AbstractThe Miocene sands of the Swiss Jura Mountains, long exploited in quarries for the construction industry, have yielded abundant fossil remains of large mammals. Among Deinotheriidae (Proboscidea), two species,Prodeinotherium bavaricumandDeinotherium giganteum, had previously been identified in the Delémont valley, but never described. A third species,Deinotherium levius, from the locality of Charmoille in Ajoie, is reported herein for the first time in Switzerland. These occurrences are dated from the middle to the late Miocene, correlating to the European Mammal biozones MN5 to MN9. The study is completed by a discussion on the palaeobiogeography of deinotheres at the European scale.
Anti-oxidant andin-vitroalpha amylase inhibitory activities of leaves and barks ofRandia dumetorum
Authors: Timalsina Deepak 
Published: August 2020

AbstractThe process of drug discovery and development in the world over a recent year has been increasingly shaped by the formulaic approaches and natural products, prioritized by popular pharmaceutical industries. In many countries like Nepal,Randia dumetorum(Maidal) is one of the popular alternatives for overcoming various symptoms such as acidity, food poisoning ulcers, diabetes and ulcers. It has been using by the people because of its wide range of therapeutic uses. Though, the considerable research had been conducted to reveal the biologically active compounds and its pharmacological effect, the rich constituent of this plant and its major biological perspective was yet to be studied comprehensively. Accordingly, the main focus of this study was the alpha amylase inhibition of methanolic extracts obtained from leaves and barks ofRandia dumetorumplant. The plant extracts were obtained by dissolving dried plant with 100% methanol overnight and evaporating to the dryness. The obtained plant extract was used to study mentioned biological activities. The results obtained showed that the extract obtained from leaves and barks showed antioxidant and alpha amylase inhibition activities. This research can be helpful to discover new types of therapeutics in the future.
A Broadly Neutralizing Macaque Monoclonal Antibody Against the HIV-1 V3-Glycan Patch
Authors: Wang Zijun , Barnes Christopher O. , Gautam Rajeev , Lorenzi Julio C. C. , Mayer Christian T. , Oliveira Thiago Y. , Ramos Victor , Cipolla Melissa , Gordon Kristie M. , Gristick Harry B. , West Anthony P. , Nishimura Yoshiaki , Raina Henna , Seaman Michael S. , Gazumyan Anna , Martin Malcolm A. , Bjorkman Pamela J. , Escolano Amelia , Nussenzweig Michel C. 
Published: August 2020

AbstractA small fraction of HIV-1 infected humans develop potent broadly neutralizing antibodies (bNAbs) against HIV-1 that can protect macaques from infection with simian immunodeficiency HIV chimeric virus (SHIV). Similarly, a small number of macaques infected with SHIVs also develop broadly neutralizing serologic activity, but less is known about the nature of these simian antibodies. Here we report on a monoclonal antibody, Ab1485, isolated from a macaque infected with SHIVAD8that developed broadly neutralizing serologic activity mapping to the V3-glycan region of HIV-1 Env. Ab1485 neutralizes 38.1 % of HIV-1 isolates in a panel of 42 pseudoviruses with a geometric mean IC50of 0.055 μg/ml and SHIVAD8with an IC50of 0.028 μg/ml. Ab1485 binds to the V3-glycan epitope in a glycan-dependent manner as determined by ELISA and neutralization assays with JRCSF mutant viruses. A 3.5 Å cryo-electron microscopy structure of Ab1485 in complex with a native-like SOSIP Env trimer showed conserved contacts with the N332gp120glycan and gp120 GDIR peptide motif, but in a distinct Env-binding orientation relative to human V3/N332gp120glycan-targeting bNAbs. Finally, intravenous infusion of Ab1485 protected macaques from a high dose intrarectal challenge with SHIVAD8. We conclude that macaques can develop bNAbs against the V3-glycan patch that resemble human V3-glycan bNAbs.Significance statementRhesus macaques infected with SHIV are an important model for evaluating HIV-1 prevention and therapy strategies and can also be used to evaluate humoral immune responses to candidate HIV-1 vaccines, but whether macaques produce human-like bNAbs has not been evaluated. Like HIV-1 infected humans, 10-20% of the SHIVAD8challenged macaques develop low levels of neutralizing antibodies, and only one macaque has developed broad and potent serologic neutralizing activity. We have examined the antibody response of this macaque (CE8J) and we report on the cloning and molecular characterization of a bNAb produced in this elite neutralizing non-human primate, its structure bound to an HIV-1 Env trimer, and the implications for development of vaccines targeting the V3-glycan patch of Env.
ViruSurf: an integrated database to investigate viral sequences
Authors: Canakoglu Arif , Pinoli Pietro , Bernasconi Anna , Alfonsi Tommaso , Melidis Damianos P. , Ceri Stefano 
Published: August 2020

ABSTRACTViruSurf, available athttp://gmql.eu/virusurf/, is a large public database of viral sequences and integrated and curated metadata from heterogeneous sources (GenBank, COG-UK and NMDC); it also exposes computed nucleotide and amino acid variants, called from original sequences. A GISAID-specific ViruSurf database, available athttp://gmql.eu/virusurf_gisaid/, offers a subset of these functionalities. Given the current pandemic outbreak, SARS-CoV-2 data are collected from the four sources; but ViruSurf contains other virus species harmful to humans, including SARS-CoV, MERS-CoV, Ebola, and Dengue.The database is centered on sequences, described from their biological, technological, and organizational dimensions. In addition, the analytical dimension characterizes the sequence in terms of its annotations and variants. The web interface enables expressing complex search queries in a simple way; arbitrary search queries can freely combine conditions on attributes from the four dimensions, extracting the resulting sequences.Several example queries on the database confirm and possibly improve results from recent research papers; results can be recomputed over time and upon selected populations. Effective search over large and curated sequence data may enable faster responses to future threats that could arise from new viruses.