bluuebunny/crossref_metadata_2025_split huggingface dataset:
Historical disturbances to rivers appear to constrain contemporary distribution of a river-dependent frog
Authors: Linnell Mark A. , Davis Raymond J. 
Published: January 2021

AbstractFrogs dependent on lotic environments are sensitive to disturbances that alter the hydrology (e.g., water impoundments), substrate (e.g., debris torrents), and riparian vegetation (e.g., wildfires) of river ecosystems. Although rivers are often very dynamic, disturbances can push environmental baselines outside of narrowly defined ecological tolerances under which a species evolved. Short-lived lotic-dependent organisms, restricted to movements within the water or the riparian corridor, are at risk of local extirpations owing to such disturbances if they fragment and isolate affected populations from recolonizing source populations. In Oregon, USA, the foothill yellow-legged frog (Rana boylii) is at its northernmost range margin and has experienced an approximately 41% range contraction compared to their historical distribution. To inform conservation and management, we used species distribution models to identify environmentally suitable watersheds based on intrinsic baseline environmental variables, and then examined potential effects of human-caused alterations to rivers, including splash dams used to ferry timber downstream prior to 1957, large water impoundments, and adjacency to agricultural croplands. We used machine-learning in program Maxent and three different river layers that varied in extent and location of mapped rivers but contained distinct information to produce species distribution models which we then combined into a single ensemble model. Stream order, annual precipitation, and precipitation frequency were the highest ranked baseline environmental variables in most models. Watersheds with highly suitable baseline conditions in our ensemble model were negatively correlated with anthropogenic disturbances to rivers. Foothill yellow-legged frogs appeared to be sensitive to human-caused disturbances to rivers, perhaps indicative of their narrow ecological tolerance to in-river conditions. We do not anticipate variables in our model to change much through time. Rather, for conservation we identified potential legacy (spash dams) and ongoing human-caused disturbances that are more likely to change conditions for the species in the short- and long-term.
Succinate Dehydrogenase (SDH)-subunit C regulates muscle oxygen consumption and fatigability in an animal model of pulmonary emphysema
Authors: Balnis Joseph , Drake Lisa A. , Vincent Catherine E. , Korponay Tanner C. , Singer Diane V. , Lacomis David , Lee Chun Geun , Elias Jack A. , Singer Harold A. , Jaitovich Ariel 
Published: January 2021

AbstractPatients with pulmonary emphysema often develop locomotor muscle dysfunction, which is independently associated with disability and higher mortality in that population. Muscle dysfunction entails reduced force-generation capacity which partially depends on fibers’ oxidative potential, yet very little mechanistic research has focused on muscle respiration in pulmonary emphysema. Using a recently established animal model of pulmonary emphysema-driven skeletal muscle dysfunction, we found downregulation of succinate dehydrogenase (SDH) subunit C in association with lower oxygen consumption and fatigue-tolerance in locomotor muscles. Reduced SDH activity has been previously observed in muscles from patients with pulmonary emphysema and we found that SDHC is required to support respiration in cultured muscle cells. Moreover,in-vivogain of SDH function in emphysema animals muscles resulted in better oxygen consumption rate (OCR) and fatigue tolerance. These changes correlated with a larger number of relatively more oxidative type 2-A and 2X fibers, and a reduced amount of 2B fibers. Our data suggests that SDHC is a key regulator of respiration and fatigability in pulmonary emphysema-driven skeletal muscles, which could be impactful to develop strategies aimed at attenuating this comorbidity.
Prioritizing and characterizing functionally relevant genes across human tissues
Authors: Somepalli Gowthami , Sahoo Sarthak , Singh Arashdeep , Hannenhalli Sridhar 
Published: January 2021

AbstractKnowledge of genes that are critical to a tissue’s function remains difficult to ascertain and presents a major bottleneck toward a mechanistic understanding of genotype-phenotype links. Here, we present the first machine learning model – FUGUE – combining transcriptional and network features, to predict tissue-relevant genes across 30 human tissues. FUGUE achieves an average cross-validation auROC of 0.86 and auPRC of 0.50 (expected 0.09). In three independent datasets, FUGUE accurately distinguishes tissue or cell type-specific genes, significantly outperforming the conventional metric based on tissue-specific expression alone. Comparison of tissue-relevant transcription factors across tissue recapitulate their developmental relationships. Interestingly, the tissue-relevant genes cluster on the genome within topologically associated domains and furthermore, are highly enriched for differentially expressed genes in the corresponding cancer type. We provide the prioritized gene lists in 30 human tissues and an open-source software to prioritize genes in a novel context given multi-sample transcriptomic data.
Performance of a scalable extraction-free RNA-seq method
Authors: Ghimire Shreya , Stewart Carley G. , Thurman Andrew L. , Pezzulo Alejandro A. 
Published: January 2021

AbstractRNA sequencing enables high-contents/high-complexity measurements in small molecule screens performed on biological samples. Whereas the costs of DNA sequencing and the complexity of RNA-seq library preparation and analysis have decreased consistently, RNA extraction remains a significant bottleneck for RNA-seq of hundreds of samples in parallel. Direct use of cell lysate for RNA-seq library prep is common in single cell RNA-seq but not in bulk RNA-seq protocols. Recently published protocols suggest that direct lysis is compatible with simplified RNA-seq library prep. Here, we evaluate the performance of a bulk RNA-seq library prep protocol optimized for analysis of many samples of adherent cultured cells in parallel. We combine a low-cost direct lysis buffer compatible with cDNA synthesis (“in-lysate cDNA synthesis”) with Smart-3SEQ and examine the effects of calmidazolium and fludrocortisone-induced perturbation of primary human dermal fibroblasts. We compared this method to normalized purified RNA inputs from matching samples followed by Smart-3SEQ or Illumina TruSeq library prep. Our results show that whereas variable RNA inputs for each sample in the in-lysate cDNA synthesis protocol result in variable sequencing depth, this had minimal effect on data quality, measurement of gene expression patterns, or generation of differentially expressed gene lists. We found that in-lysate cDNA synthesis combined with Smart-3SEQ RNA-seq library prep allows generation of high-quality data when compared to library prep with extracted RNA, or when compared to Illumina TruSeq. Our data show that small molecule screens using RNA-seq are feasible at low reagent and time costs.
Pre-diabetes linked microRNA miR-193b-3p targets PPARGC1A and increases lipid accumulation in hepatocytes: potential biomarker of fatty liver disease
Authors: Mollet Inês Guerra , Macedo Maria Paula 
Published: January 2021

AbstractDistinct plasma microRNA profiles associate with different disease features. Elevated plasma microRNA hsa-miR-193b-3p has been reported in patients with pre-diabetes where early liver dysmetabolism plays a crucial role. MicroRNA target databases revealed that hsa-miR-193b-3p could potentially target PPARGC1A, a master switch transcriptional co-activator that orchestrates the expression of genes involved in multiple metabolic pathways. In this study we evaluated the effects of hsa-miR-193b-3p in the human HepG2 hepatocyte cell line. We show that hsa-miR-193b-3p targets PPARGC1A/PGC1α mRNA 3’UTR and reduces its expression. Overexpression of hsa-miR-193b-3p under hyperglycemia resulted in increased accumulation of intracellular lipid droplets; and quantitative real-time RT-PCR of a panel of 24 genes revealed significant disruption in the expression of genes coordinating glucose uptake, glycolysis, pyruvate metabolism, fatty acid synthesis, fatty acid oxidation, triglyceride synthesis, VLDL secretion, insulin signalling, and mitochondrial biogenesis, dynamics and function. These results providein vitroevidence that microRNA hsa-miR-193b-3p downregulates PPARGC1A/PGC1α, disrupts downstream metabolic pathways and leads to the accumulation of intracellular lipids in hepatocytes. We propose that microRNA hsa-miR-193b-3p may have potential as a clinically relevant plasma biomarker for metabolic associated fatty liver disease in a pre-diabetic dysglycemic context.
An exceptionally preserved euarthropod with unique feather-like appendages from the Chengjiang biota
Authors: Zhai Dayou , Williams Mark , Siveter David J. , Siveter Derek J. , Harvey Thomas H.P. , Sansom Robert S. , Mai Huijuan , Zhou Runqing , Hou Xianguang 
Published: January 2021

AbstractMicro-CT scanning of the Cambrian euarthropodChuandianella ovatareveals unprecedented three-dimensional soft-part details. It has an elongate uniramous antennule and a short uniramous second appendage, followed by ten homonomous biramous appendages, each comprising a short paddle-shaped exopod and a unique feather-like endopod with at least 27 podomeres each of which bears a long blade-like endite with a short terminal seta. Based on its carapace and previously known soft-part anatomyC. ovatawas compared with the Burgess Shale mandibulate euarthropodWaptia. However,Waptiahas recently been shown to bear specialized head appendages that are interpreted as a mandible and maxillula, posterior to which are four appendages each with five-segmented endopods. In contrast, we interpretChuandianellaas an ‘upper’ stem-group euarthropod that possessed neither a differentiated mandible nor a maxillula.Chuandianellafurther demonstrates that early Cambrian ‘upper’ stem-group euarthropods were experimenting with a range of different limb arrangements and morphologies.
Bidirectional Associations between Short or Long Sleep Duration and Cognitive Function: the China Health and Retirement Longitudinal Study
Authors: Hua Jianian , Sun Hongpeng , Fang Qi 
Published: January 2021

AbstractIMPORTANCEThe bidirectional association between sleep duration and cognitive function has not been conclusively demonstrated.OBJECTIVETo investigate the longitudinal association between sleep duration and cognitive function among middle-aged and elderly Chinese participants.Design, SETTING, AND PARTICIPANTSA national representative and prospective longitudinal study in China. 7984 participants aged 45 years and above were assessed at baseline between June 2011 and March 2012 (wave 1) and 2013 (wave 2), 2015 (wave 3) and 2018 (wave4).MAIN OUCOMES AND MEASURESSelf-reported nighttime sleep duration was evaluated by interview. Cognitive function was evaluated via assessments of global cognition, which reflected the ability of episodic memory, visuospatial construction, calculation, orientation and attention.ResultsRegarding the 7984 participants in wave 4, the mean (SD) age was 64.7 (8.4), 3862 (48.4) were male, and 6453 (80.7) lived in rural area. There were 14981, 11768 (78.6%), 10192 (68.0%), 7984 (53.3%) participants in the four waves of the study, respectively. Latent growth models showed both sleep duration and global cognition worsen over time. Cross-lagged models indicated that long or short sleep duration in the previous wave was associated lower global cognition in the next wave (standardized β=-0.066; 95%CI: −0.073, −0.059; P<0.001; Wave 1 to 2), and lower global cognition in the previous wave was associated with long or short sleep duration in the next wave (standardized β=-0.106; 95%CI: −0.116, −0.096; P<0.001; Wave 1 to 2). Global cognition was probably the major driver in this reciprocal associations.CONCLUSIONS AND REVELANCEThere were bidirectional associations between long or short sleep duration and cognitive function. Lower cognitive function had a stronger association with worse cognitive function than the reverse. A moderate sleep duration is always recommended. Moreover, attention should be paid on the declined cognition and cognitive therapy among older adults with short or long sleep duration.
Effect of mutations in the SARS-CoV-2 spike protein on protein stability, cleavage, and cell-cell fusion function
Authors: Barrett Chelsea T. , Neal Hadley E. , Edmonds Kearstin , Moncman Carole L. , Thompson Rachel , Branttie Jean M. , Boggs Kerri Beth , Wu Cheng-Yu , Leung Daisy W. , Dutch Rebecca E. 
Published: January 2021

AbstractThe SARS-CoV-2 spike protein (S) is the sole viral protein responsible for both viral binding to a host cell and the membrane fusion event needed for cell entry. In addition to facilitating fusion needed for viral entry, S can also drive cell-cell fusion, a pathogenic effect observed in the lungs of SARS-CoV-2 infected patients. While several studies have investigated S requirements involved in viral particle entry, examination of S stability and factors involved in S cell-cell fusion remain limited. We demonstrate that S must be processed at the S1/S2 border in order to mediate cell-cell fusion, and that mutations at potential cleavage sites within the S2 subunit alter S processing at the S1/S2 border, thus preventing cell-cell fusion. We also identify residues within the internal fusion peptide and the cytoplasmic tail that modulate S cell-cell fusion. Additionally, we examine S stability and protein cleavage kinetics in a variety of mammalian cell lines, including a bat cell line related to the likely reservoir species for SARS-CoV-2, and provide evidence that proteolytic processing alters the stability of the S trimer. This work therefore offers insight into S stability, proteolytic processing, and factors that mediate S cell-cell fusion, all of which help give a more comprehensive understanding of this highly sought-after therapeutic target.
Drivers of site fidelity in ungulates
Authors: Morrison Thomas A. , Merkle Jerod A. , Hopcraft J. Grant C. , Aikens Ellen O. , Beck Jeffrey L. , Boone Randall B. , Courtemanch Alyson B. , Dwinnell Samantha P. , Fairbanks W. Sue , Griffith Brad , Middleton Arthur D. , Monteith Kevin L. , Oates Brendan , Riotte‐Lambert Louise , Sawyer Hall , Smith Kurt T. , Stabach Jared A. , Taylor Kaitlyn L. , Kauffman Matthew J. 
Published: January 2021

Abstract

While the tendency to return to previously visited locations—termed ‘site fidelity’—is common in animals, the cause of this behaviour is not well understood. One hypothesis is that site fidelity is shaped by an animal's environment, such that animals living in landscapes with predictable resources have stronger site fidelity. Site fidelity may also be conditional on the success of animals’ recent visits to that location, and it may become stronger with age as the animal accumulates experience in their landscape. Finally, differences between species, such as the way memory shapes site attractiveness, may interact with environmental drivers to modulate the strength of site fidelity.

We compared inter‐year site fidelity in 669 individuals across eight ungulate species fitted with GPS collars and occupying a range of environmental conditions in North America and Africa. We used a distance‐based index of site fidelity and tested hypothesized drivers of site fidelity using linear mixed effects models, while accounting for variation in annual range size.

Mule deer Odocoileus hemionus and moose Alces alces exhibited relatively strong site fidelity, while wildebeest Connochaetes taurinus and barren‐ground caribou Rangifer tarandus granti had relatively weak fidelity. Site fidelity was strongest in predictable landscapes where vegetative greening occurred at regular intervals over time (i.e. high temporal contingency). Species differed in their response to spatial heterogeneity in greenness (i.e. spatial constancy). Site fidelity varied seasonally in some species, but remained constant over time in others. Elk employed a ‘win‐stay, lose‐switch’ strategy, in which successful resource tracking in the springtime resulted in strong site fidelity the following spring. Site fidelity did not vary with age in any species tested.

Our results provide support for the environmental hypothesis, particularly that regularity in vegetative phenology shapes the strength of site fidelity at the inter‐annual scale. Large unexplained differences in site fidelity suggest that other factors, possibly species‐specific differences in attraction to known sites, contribute to variation in the expression of this behaviour.

Understanding drivers of variation in site fidelity across groups of organisms living in different environments provides important behavioural context for predicting how animals will respond to environmental change.
Towards a Theory of Network Facilitation: A Microfoundations Perspective on the Antecedents, Practices and Outcomes of Network Facilitation
Authors: Mueller Elisabeth F. 
Published: January 2021

AbstractFirms cooperate in inter‐firm networks to foster their competitiveness and improve their innovation outcomes. In many cases, network facilitators who are either embedded in a lead firm or a third‐party organization manage the cooperation among the network firms. This qualitative study adopts a microfoundations perspective to investigate the behavioural antecedents of the network facilitators, their facilitation practices and the related network‐level outcomes. Results show that lead‐firm facilitators more strongly invest in trust‐building measures since they are considered deficient in benevolence and integrity. Without these investments, they run the risk that conflicts of interest hinder the stimulation of positive network‐level outcomes. Third‐party facilitators, by contrast, enjoy certain credits of trust and focus on balancing firm interests from the network's activation, but need to invest in enhancing their competencies and skills with regard to the industry the firms operate in. The findings contribute to developing a theory of network facilitation by providing a nuanced understanding of how network‐level outcomes can be reduced to individual‐level factors.
Accounting for uncertainty in policy decision making: Improving access to pediatric dental care
Authors: Curry Stewart , Serban Nicoleta 
Published: January 2021

AbstractObjectiveTo introduce a statistical inference framework for policy decision making on access to pediatric dental care.Data SourcesSecondary data were collected for the state of Colorado for year 2019.Study DesignThe access model was an optimization model, matching the demand (patients) and supply (providers) of dental care. Sampling distributions of model inputs were specified using hierarchical Bayesian models, with hyperparameters informed by prior information derived from multiple data sources. Simultaneous inference was applied to identify areas for access improvement. The model was applied to make inference on the pediatric dental care in Colorado, accounting for financial access, differentiated into public (Medicaid and CHIP), private (commercial and out‐of‐pocket), and without financial access.Data Collection/Extraction MethodsMultiple data sources informed the access measurement approach including: 2017 American Community Survey, 2019 Colorado Dental Board, and 2019 National Provider Plan and Enumeration System, 2019 InsureKidsNow.gov among others.Principal FindingsThe median access measure (travel distance) was greater than the Colorado access standards in 16.9% and 65.1% of census tracts for children with private financial access and publicly insured, respectively. Accounting for uncertainty (confidence level 99%), these percentages decreased to 14.6% and 25.6%, respectively, with mostly suburban and rural tracts failing to meet the standards. The median disparity for Medicaid and CHIP versus private financial access was greater than 5 miles in 84.5% and 81.6% of census tracts, respectively. Accounting for uncertainty (confidence level 99%), these percentages declined to 19.5% and 10.5%, respectively, with significant disparities around the metropolitan areas.ConclusionsWhile many communities failed to meet access standards, when accounting for uncertainty, most urban ones did not fail. Disparities in spatial access between publicly and privately insured were most acute in urban communities. Medicaid insured experienced higher disparities than CHIP insured; those differences were not identified when not accounting for uncertainty.
Upregulation of SIX4 indicates poor clinical outcome and promotes tumor growth and cell metastasis in esophageal squamous cell carcinoma
Authors: Li Yanping , Jiang Xiaomei , Yan Xiaoyan , Wang Yanzheng 
Published: January 2021

AbstractBackgroundThe role of sine oculis homeobox 4 (SIX4) has been found in some malignant tumors. However, there have been few studies on the function of SIX4 in esophageal squamous cell carcinoma (ESCC). This study aimed to explore the regulatory mechanism of SIX4 in ESCC.MethodsRT‐qPCR and Western blot analysis were used to measure mRNA and protein expression. The function of SIX4 was investigated using CCK‐8, colony formation, flow cytometry, wound healing and transwell assays. A mouse xenograft tumor assay was designed to perform in vivo experiments.ResultsSIX4 was upregulated in ESCC and indicated poor clinical outcomes in ESCC patients. Functionally, knockdown of SIX4 inhibited cell proliferation and induced apoptosis in ESCC. In addition, the silencing of SIX4 inhibited cell migration, invasion and EMT in ESCC. More importantly, upregulation of SIX4 could activate the PI3K/AKT pathway in ESCC cells and promote tumor growth in vivo.ConclusionsUpregulation of SIX4 indicates poor clinical outcomes in ESCC patients and promotes tumor growth and cell metastasis in ESCC.
Use and outcome of empiric echinocandins in critically ill patients
Authors: Ylipalosaari Pekka , Ala‐Kokko Tero I. , Koskenkari Juha , Laurila Jouko J. , Ämmälä Sirpa , Syrjälä Hannu 
Published: January 2021

AbstractBackgroundEchinocandins are recommended as a first‐line empiric treatment for fungal infections of patients in an intensive care unit (ICU) with critical illness. The primary aim of the study was to compare outcomes among ICU patients treated with empiric anidulafungin (ANI), caspofungin (CASPO), or micafungin (MICA).MethodsA retrospective cohort study in a mixed adult ICU. Patient demographics, reason for ICU admission, ICU risk scores and organ support therapies were analyzed. Outcome parameters included ICU and hospital stay, 30‐day mortality and 1‐year mortality.ResultsEmpiric echinocandin therapy was given to 367 patients (ANI; 73 patients, CASPO; 84 patients, and MICA; 210 patients) with a median duration of 3 days in an ICU. Patient median age was 60.7 years. As a first‐line therapy, 52% of patients received fluconazole. Positive Candida cultures were found in the following samples: blood, 16 (4.4%); central line, 27 (7.4%); deep site, 92 (25.1%). Median ICU stay (ANI 6.4 days, CASPO 5.3 days, MICA 8.1 days), hospital stay (ANI 33 days, CASPO 30 days, MICA 30 days), 30‐day mortality (ANI 27%, CASPO 32%, MICA 32%), and 1‐year mortality (ANI 33%, CASPO 44%, MICA 45%) did not differ between the groups . The cost of antifungal therapy during the ICU period was similar in the three echinocandin groups (ANI; €1 872, CASPO; €1 799, and MICA; €1783).ConclusionOur results show that ICU, hospital stay, and mortality (hospital, 30‐day and 1‐year) did not differ among patients with empiric anidulafungin, caspofungin, or micafungin treatment in a mixed adult ICU.