bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Strain and Estrous Cycle on Heroin- and Sucrose-Maintained Responding in Female Rats
Authors: Schmidt Karl T. , Sharp Jessica L. , Ethridge Sarah B. , Pearson Tallia , Ballard Shannon , Potter Kenzie M. , Smith Mark A. 
Published: November 2020

AbstractHeroin intake decreases during the proestrus phase of the estrous cycle in female, Long-Evans rats. The purpose of this study was to (1) determine if proestrus-induced decreases in heroin intake extend across rat strains and (2) determine if proestrus-induced decreases in responding extend to a nondrug reinforcer. Female rats were implanted with intravenous catheters and trained to self-administer heroin. Estrous cycle was tracked daily for the duration of the study. During testing, Lewis, Sprague-Dawley, and Long Evans rats self-administered low (0.0025 mg/kg) and high (0.0075 mg /kg) doses of heroin (Experiment 1) and then self-administered sucrose (Experiment 2) on fixed ratio (FR1) schedules of reinforcement. Heroin intake decreased significantly during proestrus in all three rat strains under at least one dose condition; however, sucrose intake did not decrease during proestrus in any strain. These data indicate that responding maintained by heroin, but not a nondrug reinforcer, significantly decreases during proestrus in female rats and that these effects are consistent across rat strain.
Whole genome sequencing provides evidence of two biologically and clinically distinct entities of asymptomatic monoclonal gammopathies: progressive versus stable myeloma precursor condition
Authors: Oben Bénedith , Froyen Guy , Maclachlan Kylee H. , Leongamornlert Daniel , Abascal Federico , Zheng-Lin Binbin , Yellapantula Venkata , Derkach Andriy , Geerdens Ellen , Diamond Benjamin T. , Arijs Ingrid , Maes Brigitte , Vanhees Kimberly , Hultcrantz Malin , Manasanch Elisabet E. , Kazandjian Dickran , Dogan Ahmet , Zhang Yanming , Mikulasova Aneta , Walker Brian , Morgan Gareth , Campbell Peter J. , Landgren Ola , Rummens Jean-Luc , Bolli Niccolò , Maura Francesco 
Published: November 2020

AbstractMultiple myeloma (MM) is consistently preceded by precursor conditions recognized clinically as monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). We interrogate, for the first time, the whole genome sequence (WGS) profile of 18 MGUS and compare them with those from 14 SMMs and 80 MMs. We show that cases with a non-progressing, clinically stable myeloma precursor condition (n=15) are characterized by later initiation in the patient’s life and by the absence of myeloma defining genomic events including: chromothripsis, templated insertions, mutations in driver genes, aneuploidy, and canonical APOBEC mutational activity. This data provides evidence that WGS can be used to recognize two biologically and clinically distinct myeloma precursor entities that are either progressive or stable.
Socio-economic disparities in social distancing during the COVID-19 pandemic in the United States
Authors: Garnier Romain , Benetka Jan R. , Kraemer John , Bansal Shweta 
Published: November 2020

AbstractImportanceEliminating disparities in the burden of COVID-19 requires equitable access to control measures across socio-economic groups. Limited research on socio-economic differences in mobility hampers our ability to understand whether inequalities in social distancing are occurring during the SARS-CoV-2 pandemic.ObjectiveTo assess how mobility patterns have varied across the United States during the COVID-19 pandemic, and identify associations with socio-economic factors of populations.Design, Setting, and ParticipantsWe used anonymized mobility data from tens of millions of devices to measure the speed and depth of social distancing at the county level between February and May 2020. Using linear mixed models, we assessed the associations between social distancing and socio-economic variables, including the proportion of people below the poverty level, the proportion of Black people, the proportion of essential workers, and the population density.Main outcomes and ResultsWe find that the speed, depth, and duration of social distancing in the United States is heterogeneous. We particularly show that social distancing is slower and less intense in counties with higher proportions of people below the poverty level and essential workers; and in contrast, that social distancing is intense in counties with higher population densities and larger Black populations.Conclusions and relevanceSocio-economic inequalities appear to be associated with the levels of adoption of social distancing, potentially resulting in wide-ranging differences in the impact of COVID-19 in communities across the United States. This is likely to amplify existing health disparities, and needs to be addressed to ensure the success of ongoing pandemic mitigation efforts.
Assembly of higher-order SMN oligomers is essential for metazoan viability and requires an exposed structural motif present in the YG zipper dimer
Authors: Gupta Kushol , Wen Ying , Ninan Nisha S. , Raimer Amanda C. , Sharp Robert , Spring Ashlyn M. , Sarachan Kathryn L. , Johnson Meghan C. , Van Duyne Gregory D. , Matera A. Gregory 
Published: November 2020

AbstractProtein oligomerization is one mechanism by which homogenous solutions can separate into distinct liquid phases, enabling assembly of membraneless organelles. Survival Motor Neuron (SMN) is the eponymous component of a large macromolecular complex that chaperones biogenesis of eukaryotic ribonucleoproteins, and localizes to distinct membraneless organelles in both the nucleus and cytoplasm. SMN forms the oligomeric core of this complex, and missense mutations within its YG box domain are known to cause Spinal Muscular Atrophy (SMA). The SMN YG box utilizes a variation of the glycine zipper motif to form dimers, but the mechanism of higher-order oligomerization remains unknown. Here, we use a combination of molecular genetic, bioinformatic, biophysical, and computational approaches to show that formation of higher-order SMN oligomers depends on a set of YG box residues that are not involved in dimerization. Mutation of key residues within this new structural motif restricts assembly of SMN to dimers and causes locomotor dysfunction and viability defects in animal models.
Predicting drug resistance inM. tuberculosisusing a Long-term Recurrent Convolutional Network
Authors: Safari Amir Hosein , Sedaghat Nafiseh , Zabeti Hooman , Forna Alpha , Chindelevitch Leonid , Libbrecht Maxwell 
Published: November 2020

ABSTRACTMotivationDrug resistance in Mycobacterium tuberculosis (MTB) is a growing threat to human health worldwide. One way to mitigate the risk of drug resistance is to enable clinicians to prescribe the right antibiotic drugs to each patient through methods that predict drug resistance in MTB using whole-genome sequencing (WGS) data. Existing machine learning methods for this task typically convert the WGS data from a given bacterial isolate into features corresponding to single-nucleotide polymorphisms (SNPs) or short sequence segments of a fixed lengthK(K-mers). Here, we introduce a gene burden-based method for predicting drug resistance in TB. We define one numerical feature per gene corresponding to the number of mutations in that gene in a given isolate. This representation greatly reduces the number of model parameters. We further propose a model architecture that considers both gene order and locality structure through a Long-term Recurrent Convolutional Network (LRCN) architecture, which combines convolutional and recurrent layers.ResultsWe find that using these strategies yields a substantial, statistically significant improvement over state-of-the-art methods on a large dataset ofM. tuberculosisisolates, and suggest that this improvement is driven by our method’s ability to account for the order of the genes in the genome and their organization into operons.AvailabilityThe implementations of our feature preprocessing pipeline1and our LRCN model2are publicly available, as is our complete dataset3.Supplementary informationAdditional data are available in theSupplementary Materialsdocument4.
The diagonal band of broca regulates olfactory-mediated behaviors by modulating odor-evoked responses within the olfactory bulb
Authors: Schwarz Inna , Müller Monika , Pavlova Irina , Schweihoff Jens , Musacchio Fabrizio , Mittag Manuel , Fuhrmann Martin , Schwarz Martin K. 
Published: November 2020

AbstractSensory perception is modulated in a top-down fashion by higher brain regions to regulate the strength of its own input resulting in the adaptation of behavioral responses. In olfactory perception, the horizontal diagonal band of broca (HDB), embedded in the basal forebrain modulates olfactory information processing by recruiting olfactory bulb (OB) interneurons to shape excitatory OB output. Currently, little is known about how specific HDB to OB top-down signaling affects complex olfactory-mediated behaviors. Here we show that the olfactory bulb is strongly and differentially innervated by HDB projections. HDB-silencing via tetanus toxin light chain led to reduced odor-evoked Ca2+-responses in glomeruli of the OB, underscoring HDB’s role in odor response modulation. Furthermore, selective, light-mediated silencing of HDB to OB afferents completely prevented olfactory-mediated habituation and discrimination behaviors. Notably, also social habituation and discrimination behaviors were affected. Mono-transsynaptic tracing studies indicated a robust HDB innervation from the paraventricular nucleus (PVN). Here we provide evidence for a novel tri-synaptic PVN-HDB-OB axis responsible for modulating these types of behavior. Thus, HDB to OB projections constitute a central top-down pathway for olfactory-mediated habituation and discrimination behaviors.
TSC1loss-of-function increases risk for tauopathy by inducing tau acetylation and preventing autophagy-mediated tau clearance
Authors: Alquezar Carolina , Schoch Kathleen M , Geier Ethan G , Ramos Eliana Marisa , Scrivo Aurora , Li Kathy , Argouarch Andrea R , Mlynarski Elisabeth E , Dombroski Beth , Yokoyama Jennifer S , Cuervo Ana M , Burlingame Alma L , Schellenberg Gerard D , Miller Timothy M , Miller Bruce L , Kao Aimee W 
Published: November 2020

AbstractAge-associated neurodegenerative disorders demonstrating tau-laden intracellular inclusions, including Alzheimer’s disease (AD), frontotemporal lobar degeneration (FTLD) and progressive supranuclear palsy (PSP), are collectively known as tauopathies. The vast majority of human tauopathies accumulate non-mutant tau rather than mutant forms of the protein, yet cell and animal models for non-mutant tauopathies are lacking. We previously linked a monoallelic mutation in theTSC1gene to tau accumulation and FTLD. Now, we have identified new variants inTSC1that predisposed to other tauopathies such as AD and PSP. These newTSC1risk variants significantly decreased the half-life of TSC1/hamartinin vitro. Cellular and murine models ofTSC1haploinsufficiency (TSC1+/-) accumulated tau protein that exhibited aberrant acetylation on six lysine residues. Tau acetylation hindered its lysosomal degradation via chaperone-mediated autophagy leading to neuronal tau accumulation. Enhanced tau acetylation inTSC1+/- models was achieved through both an increase in p300 acetyltransferase activity and a decrease in SIRT1 deacetylase levels. Pharmacological modulation of either enzyme restored tau levels. Together, these studies substantiateTSC1as a novel tauopathy risk gene and advanceTSC1haploinsufficiency as a new genetic model for tauopathy. In addition, these results promote acetylated tau as a rational target for diagnostic and therapeutic modalities in multiple tauopathies.
The need for alternative plant species interaction models
Authors: Damgaard Christian , Weiner Jacob 
Published: November 2020

AbstractThe limitations of classical Lotka-Volterra models for analyzing and interpreting competitive interactions among plant species have become increasingly clear in recent years. Three problems that have been identified are (1) the absence of frequency dependence, which is important for long-term coexistence of species, (2) the need to take unmeasured (often unmeasurable) variables influencing individual performance into account (e.g. spatial variation in soil nutrients or pathogens) and (3) the need to separate measurement error from biological variation. We modify the classical Lotka-Volterra competition models to address these limitations and we fit 8 alternative models to pin-point cover data onFestuca ovinaandAgrostis capillarisover 3 years in a herbaceous plant community in Denmark, applying a Bayesian modelling framework to ascertain whether the model amendments improve the performance of the models and increase their ability to predict community dynamics and therefore to test hypotheses. Inclusion of frequency dependence and measurement error improved model performance greatly but taking possible unmeasured variables into account did not. Our results emphasize the importance of comparing alternative models in quantitative studies of plant community dynamics. Only by comparing alternative models can we identify the forces driving community assembly and change and improve our ability to predict the behavior of plant communities.
Leveraging the Mendelian Disorders of the Epigenetic Machinery to Systematically Map Functional Epigenetic Variation
Authors: Luperchio Teresa R. , Boukas Leandros , Zhang Li , Pilarowski Genay O. , Jiang Jenny , Kalinousky Allison , Hansen Kasper D. , Bjornsson Hans T. 
Published: November 2020

AbstractThe Mendelian Disorders of the Epigenetic Machinery (MDEMs) have emerged as a class of Mendelian disorders caused by loss-of-function variants in epigenetic regulators. Although each MDEM has a different causative gene, they exhibit several overlapping disease manifestations. Here, we hypothesize that this phenotypic convergence is a consequence of common abnormalities at the epigenomic level, which directly or indirectly lead to downstream convergence at the transcriptomic level. Therefore, we seek to identify abnormalities shared across multiple MDEMs, in order to pinpoint locations where epigenetic variation is causally related to disease phenotypes. To this end, we perform a comprehensive interrogation of chromatin (ATAC-Seq) and expression (RNA-Seq) states in B cells from mouse models of three MDEMs (Kabuki types 1&2 and Rubinstein-Taybi syndromes). We build on recent work in covariate-powered multiple testing to develop a new approach for the overlap analysis, which enables us to find extensive overlap primarily localized in gene promoters. We show that disruption of chromatin accessibility at promoters often leads to disruption of downstream gene expression, and identify 463 loci and 249 genes with shared disruption across all three MDEMs. As an example of how widespread dysregulation leads to specific phenotypes, we show that subtle expression alterations of multiple, IgA-relevant genes, collectively contribute to IgA deficiency in KS1 and RT1. In contrast, we predict that KS2 does not have IgA deficiency, and confirm this observationin vivo. We propose that the joint study of MDEMs offers a principled approach for systematically mapping functional epigenetic variation in mammals.
Disproportionate CH4sink strength from an endemic, sub-alpine Australian soil microbial community
Authors: McDaniel M.D. , Hernández M. , Dumont M.G. , Ingram L.J. , Adams M.A. 
Published: November 2020

AbstractSoil-to-atmosphere methane (CH4) fluxes are dependent on opposing microbial processes of production and consumption. Here we use a soil-vegetation gradient in an Australian sub-alpine ecosystem to examine links between composition of soil microbial communities, and the fluxes of greenhouse gases they regulate. For each soil-vegetation type (forest, grassland, and bog), we measured carbon dioxide (CO2) and CH4fluxes and their production/consumption at 5-cm intervals to a depth of 30 cm. All soils were sources of CO2, ranging from 49-93 mg CO2m-2h-1. Forest soils were strong net sinks for CH4at rates up to −413 µg CH4m-2h-1. Grassland soils varied with some soils acting as sources and some as sinks, but overall averaged −97 µg CH4m-2h-1. Bog soils were net sources of CH4(+340 µg CH4m-2h-1). Methanotrophs were dominated by USCα in forest and grassland soils, andCandidatusMethylomirabilis sp. in the bog soils.Methylocystiswere also detected at relatively low abundance. The potential disproportionately large contribution of these ecosystems to global CH4oxidation, and poorly understood microbial community regulating it, highlight our dependence on soil ecosystem services in remote locations can be driven by a unique population of soil microbes.Originality-Significance Statement(Identify the key aspects of originality and significance that place the work within the top 10% of current research in environmental microbiology)Novel methanotrophic bacteria have been discovered in recent years, but few studies have examined the total known diversity of methanotrophs together with the net flux of CH4from soils. We used an ecosystem with a vegetation-soil gradient in the sub-alpine regions of Australia (with extremely strong consumption of atmospheric CH4) to examine microbial and abiotic drivers of CH4fluxes across this gradient. Recently characterized methanotrophs, either USCα in forest and grassland soils, or oxygenicCandidatusMethylomirabilis sp. in the bog soil were dominant. Methanotrophs belonging to the families Methylococcaceae and Methylocystaceae represented only a small minority of the methanotrophs in this ecosystem.
The DEAD-box RNA helicase Ded1 from yeast is associated with the signal recognition particle (SRP), and its enzymatic activity is regulated by SRP21
Authors: Yeter-Alat Hilal , Belgareh-Touzé Naïma , Huvelle Emmeline , Mokdadi Molka , Banroques Josette , Kyle Tanner N. 
Published: November 2020

ABSTRACTThe DEAD-box RNA helicase Ded1 is an essential yeast protein involved in translation initiation. It belongs to the DDX3 subfamily of proteins implicated in developmental and cell-cycle regulation.In vitro, the purified Ded1 protein is an ATP-dependent RNA binding protein and an RNA-dependent ATPase, but it lacks RNA substrate specificity and enzymatic regulation. Here we demonstrate by yeast genetics,in situlocalization andin vitrobiochemical approaches that Ded1 is associated with, and regulated by, the signal recognition particle (SRP), which is a universally conserved ribonucleoprotein complex required for the co-translational translocation of polypeptides into the endoplasmic reticulum lumen and membrane. Ded1 is physically associated with SRP componentsin vivoandin vitro. Ded1 is genetically linked with SRP proteins. Finally, the enzymatic activity of Ded1 is inhibited by SRP21 with SCR1 RNA. We propose a model where Ded1 actively participates in the translocation of proteins during translation. Our results open a new comprehension of the cellular role of Ded1 during translation.
Telomere length dynamics in response to DNA damage in malaria parasites
Authors: Reed Jake , Kirkman Laura A , Kafsack Bjӧrn FC , Mason Christopher , Deitsch Kirk W 
Published: November 2020

SUMMARYMalaria remains a major cause of morbidity and mortality within the developing world. Recent work has implicated chromosome end stability and the repair of DNA breaks through telomere healing as potent drivers of variant antigen diversification, thus associating basic mechanisms for maintaining genome integrity with aspects of host-parasite interactions. Here we applied long-read sequencing technology to precisely examine the dynamics of telomere addition and chromosome end stabilization in response to double strand breaks within subtelomeric regions. We observed that the process of telomere healing induces the initial synthesis of telomere repeats well in excess of the minimal number required for end stability. However once stabilized, these newly created telomeres appear to function normally, eventually returning to a length nearing that of intact chromosome ends. These results parallel recent observations in humans, suggesting an evolutionarily conserved mechanism for chromosome end repair.
The diffusion of sustainability key performance indicators in a developing country context
Authors: Thoradeniya Prabanga , Ferreira Aldónio , Lee Janet , Tan Rebecca 
Published: November 2020

PurposeDrawing upon Abrahamson's (1991) typology of innovation diffusion, this study aims to investigate the factors underpinning diffusion of sustainability key performance indicators (SKPIs) in a developing country.Design/methodology/approachA qualitative study was conducted in Sri Lanka involving semi-structured interviews with managers, as users of SKPIs (demand-side), and both consultants and academics, as agents in diffusion process (supply-side).FindingsDiffusion of SKPIs was found to be driven by efficient-choice considerations, with fashion motives intertwined with these. The diffusion was influenced by developing country context issues relating to market competition, education, government and culture. It was somewhat surprising that market forces played a key role to the extent they did. Minimal stakeholder pressure was found to undermine the diffusion process, contrasting with developed countries in which key stakeholders act as catalysts. The developing country context appears to slow down the pace, rather than alter the pattern, of diffusion of SKPIs.Research limitations/implicationsThis study is limited by its focus on SKPI adopters, which does not permit to draw insights regarding motivations of non-adopters.Originality/valueThis study draws upon Abrahamson's typology to explore the diffusion of SKPIs in the poorly understood developing country context. The findings provide insights into driving forces behind diffusion of SKPIs, suggesting the developing country context creates “stickiness” that influences pace rather than the pattern of diffusion of SKPIs.
Preliminary research on sponge city concept for urban flood reduction: a case study on ten sponge city pilot projects in Shanghai, China
Authors: Feng Shuxian , Yamamoto Toshiya 
Published: November 2020

PurposeThis research aimed to determine the differences and similarities in each pilot project to understand the primary design forms and concepts of sponge city concept (SCC) projects in China. It also aimed to examine ten pilot projects in Shanghai to extrapolate their main characteristics and the processes necessary for implementing SCC projects effectively.Design/methodology/approachA literature review and field survey case study were employed. Data were mostly collected through a field survey in Shanghai, focusing on both the projects and the surrounding environment. Based on these projects' examination, a comparative method was used to determine the characteristics of the ten pilot SCC projects and programs in Shanghai.FindingsSix main types of SCC projects among 30 pilot cities were classified in this research to find differences and similarities among the pilot cities. Four sponge design methods were classified into ten pilot projects. After comparing each project size using the same geographical size, three geometrical types were categorized into both existing and new city areas. SCC project characteristics could be identified by combining four methods and three geometrical types and those of the SCC programs by comparing the change in land-use and the surrounding environment in ten pilot projects.Originality/valueThe results are valuable for implementing SCC projects in China and elsewhere and future research on the impact of SCC projects.