bluuebunny/crossref_metadata_2025_split huggingface dataset:
The competition dynamics of resistant and sensitive infections
Authors: Lee T. E. , Bonhoeffer S. , Penny M. A. 
Published: January 2021

AbstractAntimicrobial resistance is a major health problem with complex dynamics. Resistance may occur in an area because treated infections mutated and developed resistance, and the proportion of infections in a population may then increase. We developed a novel and flexible model that captures several features of resistance dynamics and competition. The model is able to account for many antimicrobials and thus can generally explore competition dynamics and their impact on pathogens and bacteria.Unlike simpler models, our nested model allows the population of resistant pathogen to smoothly increase or decrease. Time dependent dynamics are incorporated into difference equations which examines the effects of 12 parameters. This enables us to explicitly include three key competition dynamics: the transmission cost of resistance that occurs between hosts, the fitness cost of resistance that occurs within untreated hosts, and the release of this competition (from the fitness cost) that occurs once a host is treated. For malaria, our results suggest that without competitive release, drug resistance does not emerge. However, once emerged, competitive release has little effect, and the best way to mitigate the spread is to ensure that treatment is very effective.
Switches, stability and reversals: the evolutionary history of sexual systems in fish
Authors: Pla Susanna , Benvenuto Chiara , Capellini Isabella , Piferrer Francesc 
Published: January 2021

AbstractSexual systems are highly diverse and have profound consequences for population dynamics and resilience. Yet, little is known about how they evolved. Using phylogenetic Bayesian modelling and a sample of 4614 species, we show that gonochorism is the likely ancestral condition in teleost fish. While all hermaphroditic forms revert quickly to gonochorism, protogyny and simultaneous hermaphroditism are evolutionarily more stable than protandry. In line with theoretical expectations, simultaneous hermaphroditism does not evolve directly from gonochorism but can evolve slowly from sequential hermaphroditism, particularly protandry. We find support for the predictions from life history theory that protogynous, but not protandrous, species live longer than gonochoristic species and invest the least in male gonad mass. The distribution of teleosts’ sexual systems on the tree of life does not seem to reflect just adaptive predictions, suggesting that adaptations alone may not fully explain why some sexual forms evolve in some taxa but not others (Williams’ paradox). We propose that future studies should incorporate mating systems, spawning behaviours, and the diversity of sex determining mechanisms. Some of the latter might constrain the evolution of hermaphroditism, while the non-duality of the embryological origin of teleost gonads might explain why protogyny predominates over protandry in teleosts.
Transcranial direct current stimulation does not improve performance in a whole-body movement task
Authors: Caesley Harriet , Sewell Isabella , Gogineni Nikita , Javadi Amir-Homayoun 
Published: January 2021

AbstractResearch has investigated the use of non-invasive brain interventions, such as transcranial direct current stimulation (tDCS), to enhance motor learning and rehabilitation. Much research has shown that tDCS improves motor learning and that bilateral tDCS is more beneficial than unilateral tDCS in improving motor learning. However, past research has primarily utilised simple motor tasks in measuring motor skill learning. These are not ecologically reliable as whole-body movement is required for everyday activities. This study involved two experiments. Each experiment involved participants learning 12 Ballroom and Latin dance moves whilst undergoing tDCS. All participants underwent three sessions of tDCS, (unilateral, bilateral and sham), over three consecutive days. Participants in the first experiment (n=30) had stimulation to the primary motor cortex (PMC) and those in the second experiment (n=31) had stimulation to the dorsolateral prefrontal cortex (DLPFC). In each experiment, a baseline was taken before the training sessions and two outcome measures were taken; a day after the last training session and two weeks later. In each testing session participants’ dance ability was measured. Our results showed that bilateral tDCS impaired performance in both experiments. Unilateral stimulation impaired performance in the first experiment, and did not significantly improve performance any better than the sham stimulation in the second experiment. These results suggest that task complexity plays a crucial role when tDCS procedures are used to modulate motor performance and highlights possible limitations of tDCS in practice.
New distributional data for the northern forestfly,Lednia borealisBaumann and Kondratieff, 2010 (Plecoptera: Nemouridae), Washington, USA
Authors: Fallon Candace E. , Blevins Emilie , Blackburn Michele , Cotten Taylor B. , Stinson Derek W. 
Published: January 2021

ABSTRACTThe northern forestfly,Lednia borealis(Plecoptera: Nemouridae) is a rare montane stonefly believed to be endemic to Washington. The species, first recognized as a valid taxon in 2010, is the only member of the genusLedniaknown from the state. Like other species in its genus, it is found in mid- to high-elevation cold water habitat, including lakes, glacial-fed streams, and rheocrenes (channelized springs).Ledniaspecies in general appear to be rare or at least rarely collected. Because of their reliance on alpine and subalpine habitat,Ledniamay be especially vulnerable to threats associated with climate change. However, relatively little is known about this species, and distribution data are scarce. From 2015 to 2019, 94 sites were surveyed in order to document unmapped populations ofLednia borealisto improve range and distributional information from montane areas of Washington State. In this paper, we share locations ofL. borealisdocumented to date, including collections from eight newly documentedLedniasites in the Mt. Baker and Glacier Peak Wildernesses in the Cascade Mountains of Washington, and report recent COI barcoding results. We also provide updated details on the species’ distribution, highlight a confirmed habitat association with glacial edge meltwater, and provide recommendations for future surveys.
Hybrid Clustering of Long and Short-read for Improved Metagenome Assembly
Authors: Lu Yakang , Shi Lizhen , Van Goethem Marc W. , Sevim Volkan , Mascagni Michael , Deng Li , Wang Zhong 
Published: January 2021

ABSTRACTNext-generation sequencing has enabled metagenomics, the study of the genomes of microorganisms sampled directly from the environment without cultivation. We previously developed a proof-of-concept, scalable metagenome clustering algorithm based on Apache Spark to cluster sequence reads according to their species of origin. To overcome its under-clustering problem on short-read sequences, in this study we developed a new, two-step Label Propagation Algorithm (LPA) that first forms clusters of long reads and then recruits short reads to these clusters. Compared to alternative label propagation strategies, this hybrid clustering algorithm (hybrid-LPA) yields significantly larger read clusters without compromising cluster purity. We show that adding an extra clustering step before assembly leads to improved metagenome assemblies, predicting more complete genomes or gene clusters from a synthetic metagenome dataset and a real-world metagenome dataset, respectively. These results suggest that hybrid-LPA is a good alternative to current metagenome assembly practice by providing benefits in both scalability and accuracy on large metagenome datasets.Availability and implementationhttps://bitbucket.org/zhong_wang/hybridlpa/src/master/.Contactzhongwang@lbl.gov
Induction of Antioxidant and Detoxifying Enzymes via the Nrf2-ARE Pathway by Oriental Bezoar
Authors: Tsubonoya Tomoe , Inoue Eiji , Sudo Keiichi , Shimizu Yasuharu 
Published: January 2021

AbstractObjectivesOriental bezoar, a gallstone formed in the gall sac ofBos taurusLinné var.domesticusGmelin (Bovidae), has been used as a crude drug in oriental medicine for stroke, convulsion, epilepsy, swelling and pain in the throat, and high fever. Despite reports on the antioxidative effect of oriental bezoar-containing drugs,in vitro-cultured calculus bovis (a substitute for oriental bezoar), and its components (namely, bilirubin and biliverdin), the intracellular mechanism of the antioxidative action of oriental bezoar remains unclear. Therefore, we studied the effect of oriental bezoar on the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which transcriptionally regulates genes encoding antioxidant and detoxifying enzymes, such as heme oxygenase-1 (HO-1), glutathione-S-transferase alpha 1 (GSTA1), and quinone oxidoreductase 1 (NQO1), to elucidate its antioxidative effect.MethodsARE promoter activity and mRNA expression (HO-1, GSTA1, andNQO1) in HepG2 cells supplemented with test drugs were examinedin vitroby luciferase reporter assay and real-time PCR, respectively.ResultsOriental bezoar induced ARE promoter activity and increased the mRNA expression level ofHO-1, GSTA1, andNQO1. Its components, namely, bilirubin and biliverdin, also increased the ARE promoter activity.ConclusionThese results suggest that oriental bezoar can induce antioxidative and detoxification effects via the Nrf2-ARE pathway.
Commercial porcine gastric mucin contributes to variation in production of small molecule virulence factors byPseudomonas aeruginosawhen cultured in different formulations of artificial sputum medium
Authors: Neve Rachel L. , Carrillo Brent D. , Phelan Vanessa V. 
Published: January 2021

ABSTRACTSite-specificin vitroculture media are being developed to investigate microbial pathogenicity and ecology in nutrient environments that are more reflective of disease. For microbial ecology research in cystic fibrosis (CF), different artificial sputum media (ASM) formulations have been created to recapitulate the nutrient availability of the CF lung environment. However, these ASM formulations vary in concentration of amino acids, mucin, and other niche-specific compounds. Here, we measured the differential production of small molecule virulence factors byPseudomonas aeruginosa, the predominant pathogen in CF pulmonary infections, cultured in nine different ASM formulations via liquid chromatography tandem mass spectrometry (LC-MS/MS) and molecular networking. We show that different ASM formulations lead to different phenotypes and metabolic profiles ofP. aeruginosaand commercial porcine gastric mucin (PGM) contains a myriad of contaminants, including iron, which affectP. aeruginosaphysiology.IMPORTANCEDifferent media formulations aiming to replicatein vivoinfection environments contain different nutrients, which affects interpretation of experimental results. Inclusion of undefined components, such as commercial porcine gastric mucin (PGM), in an otherwise chemically defined medium can alter the nutrient content of the medium in unexpected ways and influence experimental outcomes.
Water, sanitation, and hygiene practices and challenges during the COVID-19 pandemic: a cross-sectional study in rural Odisha, India
Authors: Bauza Valerie , Sclar Gloria D. , Bisoyi Alokananda , Majorin Fiona , Ghugey Apurva , Clasen Thomas 
Published: January 2021

AbstractWater, sanitation, and hygiene (WASH) practices emerged as a critical component to controlling and preventing the spread of the COVID-19 pandemic. We conducted 131 semi-structured phone interviews with households in rural Odisha, India to understand behavior changes made in WASH practices as a result of the pandemic and challenges that would prevent best practices. Interviews were conducted from May-July 2020 with 73 heads of household, 37 caregivers of children less than five years old, and 21 members of village water and sanitation committees in villages with community-level piped water and high levels of latrine ownership. The majority of respondents (86%, N=104) reported a change in their handwashing practice due to COVID-19 or the related government lockdown, typically describing an increase in handwashing frequency, more thorough washing method, and/or use of soap. These improved handwashing practices remained in place a few months after the pandemic began and were often described as a new consistent practice after additional daily actions (such as returning home), suggesting new habit formation. Few participants (13%) reported barriers to handwashing. Some respondents also detailed improvements in other WASH behaviors including village-level cleaning of water tanks and/or treatment of piped water (48% of villages), household water treatment and storage (17% of respondents), and household cleaning (41% of respondents). However, there was minimal change in latrine use and child feces management practices as a result of the pandemic. We provide detailed thematic summaries of qualitative responses to allow for richer insights into these WASH behavior changes, or lack thereof, during the pandemic. The results also highlight the importance of ensuring communities have adequate WASH infrastructure to enable the practice of safe behaviors and strengthen resilience during a large-scale health crisis.
The genetic architecture of obsessive-compulsive disorder: alleles across the frequency spectrum contribute liability to OCD
Authors: Mahjani Behrang , Klei Lambertus , Mattheisen Manuel , Halvorsen Matthew W. , Reichenberg Abraham , Roeder Kathryn , Pedersen Nancy L. , Boberg Julia , de Schipper Elles , Bulik Cynthia M. , Landén Mikael , Fundín Bengt , Mataix-Cols David , Sandin Sven , Hultman Christina M. , Crowley James J. , Buxbaum Joseph D. , Rück Christian , Devlin Bernie , Grice Dorothy E. 
Published: January 2021

AbstractObjectiveObsessive-compulsive disorder (OCD) is known to be substantially heritable; however, the contribution of common genetic variation across the allele frequency spectrum to this heritability remains uncertain. We use two new, homogenous cohorts to estimate heritability of OCD from common genetic variation and contrast results with prior studies.MethodsThe sample consisted of 2096 Swedish-born individuals diagnosed with OCD and 4609 controls, all genotyped for common genetic variants, specifically >400,000 single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) ≥ 0.01. Using genotypes of these SNPs to estimate distant familial relationships among individuals, we estimated heritability of OCD, both overall and partitioned according to MAF bins.ResultsWe estimated narrow-sense heritability of 28% (SE=4%). The estimate was robust, varying only modestly under different models. Contrary to an earlier study, however, SNPs with MAF between 0.01 and 0.05 accounted for 8% of heritability and estimated heritability per bin roughly follows expectations based on a simple model for SNP-based heritability.ConclusionsThese results indicate that common inherited risk variation (MAF ≥ 0.01) accounts for most of the heritable variation in OCD. SNPs with low MAF contribute meaningfully to the heritability of OCD and the results are consistent with expectation under the “infinitesimal model,” where risk is influenced by a large number of loci across the genome and across MAF bins.
Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and meta-analysis
Authors: Castañeda-Sabogal Alex , Chambergo-Michilot Diego , Toro-Huamanchumo Carlos J. , Silva-Rengifo Christian , Gonzales-Zamora José , Barboza Joshuan J. 
Published: January 2021

AbstractBackgroundTo assess the outcomes of ivermectin in ambulatory and hospitalized patients with COVID-19.MethodsFive databases and websites for preprints were searched until January 2021 for randomized controlled trials (RCTs) and retrospective cohorts assessing ivermectin versus control in ambulatory and hospitalized participants. The primary outcome was overall mortality. Secondary outcome was recovered patients. For meta-analysis, random-effects and inverse variance meta-analyses with logarithmic transformation were performed. ROBINS-I for cohort studies, and the Cochrane Risk of Bias 2.0 tool for trials were used. The strength of evidence was assessed using GRADE.ResultsAfter the selection, twelve studies (five retrospective cohort studies, six randomized clinical trials and one case series), were included. In total, 7412 participants were reported, the mean age was 47.5 (SD 9.5) years, and 4283 (58%) were male. Ivermectin was not associated with reduced mortality (logRR: 0.89, 95% CI 0.09 to 1.70, p = 0.04, I2= 84.7%), or reduced patient recovery (logRR 5.52, 95% CI -24.36 to 35.4, p = 0.51, I2= 92.6%). All studies had a high risk of bias, and showed a very low certainty of the evidence.ConclusionsThere insufficient certainty and quality of evidence to recommend the use of ivermectin to prevent or treat ambulatory or hospitalized patients with COVID-19.
Unsupervised discovery of dynamic cell phenotypic states from transmitted light movies
Authors: Nguyen Phuc H.B. , Chien Sylvia , Dai Jin , Monnat Raymond J. , Becker Pamela S , Kueh Hao Yuan 
Published: January 2021

SummaryIdentification of cell phenotypic states within heterogeneous populations, along with elucidation of their switching dynamics, is a central challenge in modern biology. Conventional single-cell analysis methods typically provide only indirect, static phenotypic readouts. Transmitted light images, on the other hand, provide direct morphological readouts and can be acquired over time to provide a rich data source for dynamic cell phenotypic state identification. Here, we describe an end-to-end deep learning platform, UPSIDE (for Unsupervised Phenotypic State IDEntification), for discovering cell states and their dynamics from transmitted light movies.UPSIDE uses the variational auto-encoder architecture to learn latent cell representations, that are then clustered for state identification, decoded for feature interpretation, and linked across movie frames for transition rate inference. Using UPSIDE, we identified distinct blood cell types in a heterogeneous dataset. From acute myeloid leukemia cell movies, we then identified stem-cell associated morphological states and their inter-conversion rates. UPSIDE opens up use of transmitted light movies for systematic exploration of cell state heterogeneity and dynamics in biology and medicine.
Molecular mechanism of a parasite kinesin motor and implications for its inhibition
Authors: Cook Alexander D. , Roberts Anthony , Atherton Joseph , Tewari Rita , Topf Maya , Moores Carolyn A. 
Published: January 2021

ABSTRACTPlasmodiumparasites cause malaria and are responsible annually for hundreds of thousands of deaths. They have a complex life cycle in which distinct stages are transmitted between, and reproduce in, human and mosquito hosts. In the light of emerging resistance to current therapies, components of the parasite replicative machinery are potentially important targets for anti-parasite drugs. Members of the superfamily of kinesin motors play important roles in the microtubule-based replicative spindle machinery, and kinesin-5 motors are established anti-mitotic targets in other disease contexts. We therefore studied kinesin-5 fromPlasmodium falciparum(PfK5) and characterised the biochemical properties and structure of thePfK5 motor domain. We found that thePfK5 motor domain is an ATPase with microtubule plus-end directed motility. We used cryo-EM to determine the motor’s microtubule-bound structure in no nucleotide and AMPPNP-bound states. Despite significant sequence divergence in this motor, these structures reveal that this parasite motor exhibits classical kinesin mechanochemistry. This includes ATP-induced neck-linker docking to the motor domain, which is consistent with the motor’s plus-ended directed motility. Crucially, we also observed that a large insertion in loop5 of thePfK5 motor domain creates a dramatically different chemical environment in the well characterised human kinesin-5 drug-binding site. Our data thereby reveal the possibility for selective inhibition ofPfK5 and can be used to inform future exploration ofPlasmodiumkinesins as anti-parasite targets.
Phenotypic plasticity is aligned with phenological adaptation on both micro- and macroevolutionary timescales
Authors: De Lisle Stephen P. , Mäenpää Maarit I. , Svensson Erik I. 
Published: January 2021

AbstractIn seasonally-variable environments, phenotypic plasticity in phenology may be critical for adaptation to fluctuating environmental (temperature) conditions. Using an 18-generation longitudinal dataset from natural insect (damselfly) populations, we show that phenology has strongly advanced. Individual fitness data suggest this is likely an adaptive response towards a thermally-dependent fitness optimum. A laboratory experiment revealed that developmental plasticity qualitatively matches environmental-dependence of selection, partially explaining observed phenological advance. Expanding our analysis to the macroevolutionary level, we use a database of over 1-million occurrence records and spatiotemporally-matched temperature data from 49 Swedish Odonate species to infer macroevolutionary dynamics of phenology. Phenological plasticity was more closely aligned with adaptation for species that have recently colonized northern latitudes, with more phenological mismatch at lower latitudes. Our results show that phenological plasticity plays a key role in microevolutionary dynamics within a single species, and such plasticity may have facilitated post-Pleistocene range expansion in this insect clade.
Novel method for quantifying AhR-ligand binding affinities using Microscale Thermophoresis
Authors: Stinn Anne , Furkert Jens , Kaufmann Stefan H.E. , Moura-Alves Pedro , Kolbe Michael 
Published: January 2021

AbstractThe aryl hydrocarbon receptor (AhR) is a highly conserved cellular sensor of a variety of environmental pollutants and dietary-, cell- and microbiota-derived metabolites with important roles in fundamental biological processes. Deregulation of the AhR pathway is implicated in several diseases, including autoimmune diseases and cancer, rendering AhR a promising target for drug development and host-directed therapy. The pharmacological intervention of AhR processes requires detailed information about the ligand binding properties to allow specific targeting of a particular signalling process without affecting the remaining. Here, we present a novel microscale thermophoresis-based approach to monitoring the binding of purified recombinant human AhR to its natural ligands in a cell-free system. This approach facilitates a precise identification and characterization of unknown AhR ligands and represents a screening strategy for the discovery of potential selective AhR modulators.