bluuebunny/crossref_metadata_2025_split huggingface dataset:
Canada’s human footprint reveals large intact areas juxtaposed against areas under immense anthropogenic pressure
Authors: Hirsh-Pearson Kristen , Johnson Chris J. , Schuster Richard , Wheate Roger D. , Venter Oscar 
Published: June 2021

AbstractEfforts are underway in Canada to set aside terrestrial lands for conservation, thereby protecting them from anthropogenic pressures. Here we produce the first Canadian human footprint map to identify intact and modified lands and ecosystems. Our results showed strong spatial variation in pressures across the country, with just 18% of Canada experiencing measurable human pressure. However, some ecosystems are experiencing very high pressure, such as the Great Lakes Plains and Prairies national ecological areas which have over 75% and 56% of their areas, respectively, with a high human footprint. In contrast, the Arctic and Northern Mountains have less than 0.02% and 0.2% under high human footprint. A validation of the final map resulted in a Cohen Kappa statistic of 0.911, signifying an ‘almost perfect’ agreement between the human footprint and the validation data set. By increasing the number and accuracy of mapped pressures, our map demonstrates much more widespread pressures in Canada than were indicated by previous global mapping efforts, demonstrating the value in specific national data applications. Ecological areas with immense anthropogenic pressure, highlight challenges that may arise when planning for ecologically representative protected areas.
Heterogeneity in effective size across the genome: effects on the Inverse Instantaneous Coalescence Rate (IICR) and implications for demographic inference under linked selection
Authors: Boitard Simon , Arredondo Armando , Noûs Camille , Chikhi Lounès , Mazet Olivier 
Published: June 2021

AbstractThe relative contribution of selection and neutrality in shaping species genetic diversity is one of the most central and controversial questions in evolutionary theory. Genomic data provide growing evidence that linked selection, i.e. the modification of genetic diversity at neutral sites through linkage with selected sites, might be pervasive over the genome. Several studies proposed that linked selection could be modelled as first approximation by a local reduction (e.g. purifying selection, selective sweeps) or increase (e.g. balancing selection) of effective population size (Ne). At the genome-wide scale, this leads to variations ofNefrom one region to another, reflecting the heterogeneity of selective constraints and recombination rates between regions. We investigate here the consequences of such genomic variations ofNeon the genome-wide distribution of coalescence times. The underlying motivation concerns the impact of linked selection on demographic inference, because the distribution of coalescence times is at the heart of several important demographic inference approaches. Using the concept of Inverse Instantaneous Coalescence Rate, we demonstrate that in a panmictic population, linked selection always results in a spurious apparent decrease ofNealong time. Balancing selection has a particularly large effect, even when it concerns a very small part of the genome. We also study more general models including genuine population size changes, population structure or transient selection and find that the effect of linked selection can be significantly reduced by that of population structure. The models and conclusions presented here are also relevant to the study of other biological processes generating apparent variations ofNealong the genome.
Interpretable modeling of genotype-phenotype landscapes with state-of-the-art predictive power
Authors: Tonner Peter D. , Pressman Abe , Ross David 
Published: June 2021

AbstractLarge-scale measurements linking genetic background to biological function have driven a need for models that can incorporate these data for reliable predictions and insight into the underlying biochemical system. Recent modeling efforts, however, prioritize predictive accuracy at the expense of model interpretability. Here, we present LANTERN (https://github.com/usnistgov/lantern), a hierarchical Bayesian model that distills genotype-phenotype landscape (GPL) measurements into a low-dimensional feature-space that represents the fundamental biological mechanisms of the system while also enabling straightforward, explainable predictions. Across a benchmark of large-scale datasets, LANTERN equals or outperforms all alternative approaches, including deep neural networks. LANTERN furthermore extracts useful insights into the landscape including its inherent dimensionality, a latent space of additive mutational effects, and novel metrics of landscape structure. LANTERN facilitates straightforward discovery of fundamental mechanisms in GPLs, while also reliably extrapolating to unexplored regions of genotypic-space.
Monoclonal antibodies against cell wall chitooligomers as accessory tools for the control of cryptococcosis
Authors: Figueiredo Alexandre Bezerra Conde , Fonseca Fernanda L. , de Paiva Conte Fernando , Arissawa Marcia , Rodrigues Marcio L. 
Published: June 2021

AbstractTherapeutic strategies against systemic mycoses can involve antifungal resistance and significant toxicity. Thus, novel therapeutic approaches to fight fungal infections are urgent. Monoclonal antibodies (mAbs) are promising tools to fight systemic mycoses. In this study, mAbs of the IgM isotype were developed against chitin oligomers. Chitooligomers derive from chitin, an essential component of the fungal cell wall and a promising therapeutic target, as it is not synthesized by humans or animals. Surface plasmon resonance (SPR) assays and cell-binding tests showed that the mAbs recognizing chitooligomers have high affinity and specificity for the chitin derivatives. In vitro tests showed that the chitooligomer mAbs increased the fungicidal capacity of amphotericin B against Cryptococcus neoformans. The chitooligomer-binding mAbs interfered with two essential properties related to cryptococcal pathogenesis: biofilm formation and melanin production. In a murine model of C. neoformans infection, the combined administration of the chitooligomer-binding mAb and subinhibitory doses of amphotericin B promoted disease control. The data obtained in this study support the hypothesis that chitooligomer antibodies are of great potential as accessory tools in the control of cryptococcosis.
Evolution of Selective RNA Processing and Stabilization operons in cellulosome-harboring Clostridium spp
Authors: Bhaskar Yogendra , Heidari B. Mohammadhadi , Xu Chenggang , Xu Jian 
Published: June 2021

AbstractIn selective RNA processing and stabilization (SRPS) operons, the stoichiometry of encoded proteins is determined by their respective 3’-end stem-loops (SLs), yet the evolution of this mechanism remains elusive. In cellulosomal operons of Clostridium spp., we show that the SLs and their associated genes form a monogamy companionship during the operon evolution. Based on ΔG of such SLs, we propose CoSLOE (Composite SL-based Operon Evolution) model with evolutionary ratio (ER) >1 or <1 for positive or negative selection of SRPS operons. In the composite SL-ΔG-based tree (CoSL-tree) of cellulosomal operons, when traversing from leafs to the root nodes, ERs reveal diversifying/positive selection towards a less efficient cellulosomal system, consistent with glycoside-hydrolase gene variation both in-operon and genome-wide. A similar pattern is followed by the ATPase operon and the majority of orthologous SRPS operons genome-wide, suggesting conservation among operons in such selection. Thus SRPS operons via their transcript-stabilizing non-coding elements are highlighting a link between operon stoichiometry and operon evolution.
Genetic structure in patchy populations of a candidate foundation plant: a case study ofLeymus chinensis(Poaceae) using genetic and clonal diversity
Authors: Guo Jian , Richards Christina L. , Holsinger Kent E. , Fox Gordon A. , Zhang Zhuo , Zhou Chan 
Published: June 2021

ABSTRACTPREMISEThe distribution of genetic diversity on the landscape has critical ecological and evolutionary implications. This may be especially the case on a local scale for foundation plant species since they create and define ecological communities, contributing disproportionately to ecosystem function.METHODSWe examined the distribution of genetic diversity and clones, which we defined first as unique multi-locus genotypes (MLG), and then by grouping similar MLGs into multi-locus lineages (MLL). We used 186 markers from inter-simple sequence repeats (ISSR) across 358 ramets from 13 patches of the foundation grassLeymus chinensis. We examined the relationship between genetic and clonal diversities, their variation with patch-size, and the effect of the number of markers used to evaluate genetic diversity and structure in this species.RESULTSEvery ramet had a unique MLG. Almost all patches consisted of individuals belonging to a single MLL. We confirmed this with a clustering algorithm to group related genotypes. The predominance of a single lineage within each patch could be the result of the accumulation of somatic mutations, limited dispersal, some sexual reproduction with partners mainly restricted to the same patch, or a combination of all three.CONCLUSIONSWe found strong genetic structure among patches ofL. chinensis. Consistent with previous work on the species, the clustering of similar genotypes within patches suggests that clonal reproduction combined with somatic mutation, limited dispersal, and some degree of sexual reproduction among neighbors causes individuals within a patch to be more closely related than among patches.
Glycolytic inhibitor 2-Deoxy-D-glucose attenuates SARS-CoV-2 multiplication in host cells and weakens the infective potential of progeny virions
Authors: Bhatt Anant Narayan , Kumar Abhishek , Rai Yogesh , Kumari Neeraj , Vedagiri Dhiviya , Harshan Krishnan H. , Chinnadurai Vijayakumar , Chandna Sudhir 
Published: June 2021

AbstractThe COVID-19 pandemic is an ongoing public health emergency of international concern. While a lot of efforts are being invested in vaccinating the population, there is also an emergent requirement to find potential therapeutics to effectively counter this fast mutating SARS-CoV-2 virus-induced pathogenicity. Virus-infected host cells switch their metabolism to a more glycolytic phenotype. This switch induced by the virus is needed for faster production of ATP and higher levels of anabolic intermediates, required for new virion synthesis and packaging. In this study, we used 2-Deoxy-D-glucose (2-DG) to target and inhibit the metabolic reprogramming induced by SARS-CoV-2 infection. Our results showed that virus infection induces glucose influx and glycolysis resulting in selective high accumulation of the fluorescent glucose/2-DG analogue, 2-NBDG in these cells. Subsequently, 2-DG inhibits glycolysis in infected cells thereby reducing the virus multiplication and alleviates the cells from virus induced cytopathic effect (CPE) and cell death. Herein, we demonstrate that the crucial Nglycosites (N331 and N343) of RBD in spike protein of progeny virions produced from 2-DG treated cells were found unglycosylated and defective with compromised infectivity potential. In line with earlier reported observations, our study also showed that 2-DG mediated metabolic inhibiton can attenuate SARS-COV-2 multiplication. In addition, mechanistic study revealed that the inhibition of SARS-COV-2 multiplication is attributed to 2-DG induced un-glycosylation of spike protein. Our findings strengthen the notion that 2-DG effectively inhibits SARS-CoV-2 multiplication. Therefore, based on its previous human trials in different types of Cancer and Herpes patients, it could be a potential molecule to study in COVID-19 patients.
Tangential high-density electrode insertions allow to simultaneously measure neuronal activity across an extended region of the visual field in mouse superior colliculus
Authors: Sibille Jérémie , Gehr Carolin , Teh Kai Lun , Kremkow Jens 
Published: June 2021

AbstractThe superior colliculus (SC) is a midbrain structure that plays a central role in visual processing. Although we have learned a considerable amount about the function of single SC neurons, the way in which sensory information is represented and processed on the population level in awake behaving animals and across a large region of the retinotopic map is still largely unknown. Partially because the SC is anatomically located below the cortical sheet and the transverse sinus, it is technically difficult to measure neuronal activity from a large population of neurons in SC. To address this, we propose a tangential recording configuration using high-density electrode probes (Neuropixels) in mouse SC in vivo that permits a large number of recording sites (~200) accessibility inside the SC circuitry. This approach thereby provides a unique opportunity to measure the activity of SC neuronal populations composing up to ~2 mm of SC tissue and characterized by receptive fields covering an extended region in the visual field. Here we describe how to perform tangential recordings along the anterior-posterior and the medio-lateral axis of the mouse SC in vivo and how to combine this approach with optogenetic tools for cell-type identification on the population level.
Exposure route, sex, and age influence disease outcome in a golden Syrian hamster model of SARS-CoV-2 infection
Authors: Griffin Bryan D. , Warner Bryce M. , Chan Mable , Mendoza Emelissa J. , Tailor Nikesh , Banadyga Logan , Leung Anders , He Shihua , Boese Amrit S. , Audet Jonathan , Cao Wenguang , Moffat Estella , Garnett Lauren , Tierney Kevin , Tran Kaylie N. , Albietz Alixandra , Manguiat Kathy , Soule Geoff , Bello Alexander , Vendramelli Robert , Lin Jessica , Deschambault Yvon , Zhu Wenjun , Safronetz David , Wood Heidi , Mubareka Samira , Strong James E. , Embury-Hyatt Carissa , Kobasa Darwyn 
Published: June 2021

AbstractThe emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resultant pandemic of coronavirus disease 2019 (COVID-19) has led to over one hundred million confirmed infections, greater than three million deaths, and severe economic and social disruption. Animal models of SARS-CoV-2 are critical tools for the pre-clinical evaluation of antivirals, vaccines, and candidate therapeutics currently under urgent development to curb COVID-19-associated morbidity and mortality. The golden (Syrian) hamster model of SARS-CoV-2 infection recapitulates key characteristics of severe COVID-19, including high-titer viral replication in the upper and lower respiratory tract and the development of pathogenic lesions in the lungs. In this work we examined the influence of the route of exposure, sex, and age on SARS-CoV-2 pathogenesis in golden hamsters. We report that delivery of SARS-CoV-2 primarily to the nasal passages (low-volume intranasal), the upper and lower respiratory tract (high-volume intranasal), or the digestive tract (intragastric) results in comparable viral titers in the lung tissue and similar levels of viral shedding during acute infection. However, low-volume intranasal exposure results in milder weight loss during acute infection while intragastric exposure leads to a diminished capacity to regain body weight following the period of acute illness. Further, we examined both sex and age differences in response to SARS-CoV-2 infection. Male hamsters, and to a greater extent older male hamsters, display an impaired capacity to recover from illness and a delay in viral clearance compared to females. Lastly, route of exposure, sex, and age were found to influence the nature of the host inflammatory cytokine response, but they had a minimal effect on both the quality and durability of the humoral immune response as well as the susceptibility of hamsters to SARS-CoV-2 re-infection. Together, these data indicate that the route of exposure, sex, and age have a meaningful impact SARS-CoV-2 pathogenesis in hamsters and that these variables should be considered when designing pre-clinical challenge studies.
Monitoring fish spawning sites in freshwater ecosystems using low-cost UAV data: A case study of salmonids in lakes in Iceland
Authors: Ponsioen Lieke , Kapralova Kalina H. , Holm Fredrik , García Martínez Silvia , Hennig Benjamin D. 
Published: June 2021

AbstractLow-cost unmanned aerial vehicles (UAV), widely known as drones, have become ubiquitous and improved considerably in their technical capabilities and data quality. This opens new opportunities for their utilisation in scientific research that can help to reduce equipment and data collection costs. Remote sensing methods in ecological fieldwork can be a suitable approach to complementing, augmenting or even replacing certain aspects of fieldwork. In this study we tested the suitability of UAV for the detection of salmonid spawning grounds in two lakes in Iceland, Thingvallavatn and Ellidavatn. Salmonids are very susceptible to environmental changes, especially during embryonic development when highly oxygenated water flow and low temperatures are required. Monitoring the changes of the redd density over time will help understand the population dynamics of salmonid species and create strategies for species conservation. As part of this pilot study, we conducted aerial surveys during the spawning seasons in both locations in 2018 recording standard photographs in the visible spectrum (red, green, blue) to fully cover the respective areas of interest. Different flight altitudes were recorded to test the effects of image resolution on the final analyses. The images were then processed by applying standard remote sensing analyses in the software ENVI. The maximum likelihood classification combined with post-classification improvement methods resulted in satisfactory accuracies that are valuable for further monitoring efforts. From these findings we established a workflow that allows the implementation of UAV in ecological fieldwork for regular long-term observations. We discuss our experiences with regards to their utility, their limitations and identify future directions of research for implementing the potential that low-cost approaches have in supporting ecological studies of freshwater ecosystems.
Transcriptome features of striated muscle aging and predictability of protein level changes
Authors: Han Yu , Li Lauren Z. , Kastury Nikhitha L. , Thomas Cody T , Lam Maggie P. Y. , Lau Edward 
Published: June 2021

AbstractRNA and protein levels correlate only partially and some transcripts are better correlated with their protein counterparts than others. This suggests that in aging and disease studies, some transcriptomics markers may carry more information in predicting protein-level changes. Here we applied a computational data analysis workflow to predict which transcriptomic changes are more likely relevant to protein-level regulation in striated muscle aging. The protein predictability of each transcript is estimated from existing large proteogenomics data sets, then transferred to new total RNA sequencing data comparing skeletal muscle and cardiac muscle in young adult (~4 months) mice vs. early aging (~20 months) mice. Aging cardiac and skeletal muscles both invoke transcriptomic changes in innate immune system and mitochondria pathways but diverge in extracellular matrix processes. On an individual gene level, we identified 611 age-associated signatures in skeletal and cardiac muscles at 10% FDR, including a number of myokine and cardiokine encoding genes. We estimate that about 48% of the aging-associated transcripts may predict protein levels well (r ≥ 0.5). In parallel, a comparison of the identified aging-regulated genes with public human transcriptomics data showed that only 35–45% of the identified genes show an age-dependent expression in corresponding human tissues. Finally, integrating both RNA-protein correlation and human conservation across data sources, we nominate 134 prioritized aging striated muscle signature genes that are predicted to correlate strongly with protein levels and that show age-dependent expression in humans. These prioritized signatures may hold promise to understanding heart and skeletal muscle physiology in human and mouse aging.
Coordinated multivoxel coding beyond univariate effects is not likely to be observable in fMRI data
Authors: Pakravan Mansooreh , Ghazizadeh Ali 
Published: June 2021

ABSTRACTSimultaneous recording of activity across brain regions can contain additional information compared to regional recordings done in isolation. In particular, multivariate pattern analysis (MVPA) across voxels has been interpreted as evidence for distributed coding of cognitive or sensorimotor processes beyond what can be gleaned from a collection of univariate responses (UVR) using functional magnetic resonance imaging (fMRI). Here, we argue that regardless of patterns revealed, conventional MVPA is merely a decoding tool with increased sensitivity arising from considering a large number of ‘weak classifiers’ (i.e. single voxels) in higher dimensions. We propose instead that ‘real’ multivoxel coding should result in changes in higher-order statistics across voxels between conditions such as second-order multivariate responses (sMVR). Surprisingly, analysis of conditions with robust multivariate responses (MVR) revealed by MVPA failed to show significant sMVR in two species (humans and macaques). Further analysis showed that while both MVR and sMVR can be readily observed in the spiking activity of neuronal populations, the slow and nonlinear hemodynamic coupling and low spatial resolution of fMRI activations make the observation of higher-order statistics between voxels highly unlikely. These results reveal inherent limitations of fMRI signals for studying coordinated coding across voxels. Together, these findings suggest that care should be taken in interpreting significant MVPA results as representing anything beyond a collection of univariate effects.
NMPylation and de-NMPylation of SARS-CoV-2 Nsp9 by the NiRAN domain
Authors: Wang Bing , Svetlov Dmitri , Artsimovitch Irina 
Published: June 2021

ABSTRACTNsp12, the catalytic subunit of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), contains two active sites that catalyze nucleotidyl-monophosphate (NMP) transfer (NMPylation). RNA synthesis is mediated by the RdRp active site that is conserved among all RNA viruses and has been a focus of mechanistic studies and drug discovery. The second active site resides in a Nidovirus RdRp-Associated Nucleotidyl transferase (NiRAN) domain. Both catalytic reactions are essential for viral replication, but the mechanism and targets of NiRAN are poorly characterized. One recent study showed that NiRAN transfers NMP to the first residue of RNA-binding protein Nsp9. Another study reported a structure of SARS-CoV-2 replicase with an extended Nsp9 in the NiRAN active site but observed NMP transfer to RNA instead. We show that SARS-CoV-2 Nsp12 efficiently and reversibly NMPylates the native but not the extended Nsp9. Substitutions of the invariant NiRAN residues abolish NMPylation, whereas a substitution of a catalytic RdRp Asp residue does not. NMPylation is inhibited by nucleotide analogs, pyrophosphate, and bisphosphonates, suggesting a path for rational design of NiRAN inhibitors. We hypothesize that Nsp9 remodels both active sites of Nsp12 to support initiation of RNA synthesis by RdRp and subsequent capping of the product RNA by the NiRAN domain.