bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic variation and population histories of spotted (Strix occidentalis) and barred (S. varia) owls
Authors: Fujito Naoko T. , Hanna Zachary R. , Levy-Sakin Michal , Bowie Rauri C. K. , Kwok Pui-Yan , Dumbacher John P. , Wall Jeffrey D. 
Published: February 2020

AbstractSpotted owls (SO,Strix occidentalis) are a keystone species inhabiting old-growth forests in Western North America. In recent decades, their populations have declined due to ongoing reductions in suitable habitat caused by logging, wildfires, and competition with the congeneric barred owl (BO,Strix varia). The northern spotted owl (subspeciesS. o. caurina) has been listed as “threatened” under the Endangered Species Act since 1990. Here we present a comprehensive look at genetic variation to elucidate the population histories of SO and invading western BO. Specifically, we present an improved SO genome assembly, based on 10x and Bionano Genomics data, along with 51 high-coverage whole-genome sequences including 11 SO from two subspecies (caurinaandoccidentalis), 25 BO, 2 confirmed and 13 potential hybrids. We identified potential hybrids based on intermediate morphology and found them to be a mixture of pure BO, F1 hybrids, and F1 x BO backcrosses. Unlike previous studies reporting asymmetries in the species-specific genders of the parents of F1 hybrids, we did not observe any significant asymmetry. Within species, we found that Western BO genetic variation is not simply a subset of the genetic variation in Eastern BO, suggesting that the two groups have been genetically isolated for longer (thousands of years) than previously suspected (80-130 years). Similarly, we found evidence of substantial genetic differentiation between the two SO subspecies. Finally, our analyses suggest that Northern SO experienced a moderate population bottleneck around the end of the last glaciation, while BO population sizes have always been large.
Thioesterase Superfamily Member 1 Undergoes Stimulus-coupled Reorganization to Regulate Metabolism
Authors: Li Yue , Imai Norihiro , Goyal Samaksh , Nicholls Hayley T. , Krisko Tibor I. , Baqai Mahnoor , Ang Lay-Hong , Tillman Matthew C. , Ortlund Eric A. , Cohen David E. , Hagen Susan J. 
Published: February 2020

AbstractIn brown adipose tissue, cold exposure promotes thermogenesis, in large part by increasing mitochondrial β-oxidation of lipid droplet-derived fatty acids. This process is suppressed by thioesterase superfamily member 1 (Them1), a long chain fatty acyl-CoA thioesterase that is highly upregulated by cold ambient temperatures. Them1 reduces fatty acid availability for β-oxidation in mitochondria and limits thermogenesis by cellular mechanisms that are not well defined. We show that Them1 regulates metabolism by undergoing marked intracellular conformational changes that occur in response to β-adrenergic stimulation. Mechanistically, Them1 formed puncta that were localized near LD and mitochondria in an immortalized brown adipose cell line. In response to stimulation by norepinephrine, Them1 was phosphorylated by PKCβ at S15, which specifically inhibited puncta formation and resulted in a diffuse intracellular localization. This change in Them1 localization also occurred after stimulation in vivo. Puncta formation activated Them1 metabolic activity in vitro, as evidenced by suppression of oxygen consumption following β-adrenergic stimulation. We show by correlative light and electron microscopy that puncta are biomolecular condensates (also known as membraneless organelles) that typically form by phase separation. Them1 contains one intrinsically disordered region at the N-terminus with multiple interacting motifs that is frequently observed in phase-separating proteins. Phosphorylation, which is known to disrupt phase separation and aggregation, results in a diffuse Them1 localization. Our data thus establish that Them1 forms intracellular biomolecular condensates that limit fatty acid oxidation and suppress thermogenesis. During a period of energy demand, the condensates are disrupted by phosphorylation to allow for maximal thermogenesis. The stimulus-coupled reorganization of Them1 thus provides fine-tuning of thermogenesis and energy expenditure.
The Gene Expression Profile of UropathogenicEscherichia coliin Women with Uncomplicated Urinary Tract Infections Is Recapitulated in the Mouse Model
Authors: Frick-Cheng Arwen E. , Sintsova Anna , Smith Sara N. , Krauthammer Michael , Eaton Kathryn A. , Mobley Harry L. T. 
Published: February 2020

AbstractUropathogenicEscherichia coli(UPEC) is the primary causative agent of uncomplicated urinary tract infections (UTIs). UPEC fitness and virulence determinants have been evaluated in a variety of laboratory settings that include a well-established mouse model of UTI. However, the extent to which bacterial physiology differs between experimental models and human infections remains largely understudied. To address this important question, we compared the transcriptomes of three different UPEC isolates in human infection and a variety of laboratory conditions including LB culture, filter-sterilized urine culture, and the UTI mouse model. We observed high correlation in gene expression between the mouse model and human infection in all three strains examined (Pearson correlation coefficient of 0.86-0.87). Only 175 of 3,266 (5.4%) genes shared by all three strains had significantly different expression levels, with the majority of them (145 genes) down-regulated in patients. Importantly, gene expression of both canonical virulence factors and metabolic machinery were highly similar between the mouse model and human infection, while thein vitroconditions displayed more substantial differences. Interestingly, comparison of gene expression between the mouse model and human infection hint at differences in bladder oxygenation as well as nutrient composition. In summary, our work strongly validates the continued use of this mouse model for the study of the pathogenesis of human UTI.ImportanceDifferent experimental models have been used to study UPEC pathogenesis includingin vitrocultures in different media, tissue culture, as well as mouse models of infection. The latter is especially important since it allows evaluation of mechanisms of pathogenesis and potential therapeutic strategies against UPEC. Bacterial physiology is greatly shaped by environment and it is therefore critical to understand how closely bacterial physiology in any experimental model relates to human infection. In this study, we found a very strong correlation in bacterial gene expression between the mouse model and human UTI using identical strains, suggesting that the mouse model accurately mimics human infection, definitively supporting its continued use in UTI research.
Anethole dithiolethione improves liver fatty acid metabolism in hamster fed high-fat diets
Authors: Zhao Chengcheng , Yu Nannan , Li Wenqun , Cai Hualin , Liu Mouze , Hu Yanjie , Liu Yiping , Tang Mimi 
Published: February 2020

Abstract“Lipotoxicity” induced by excessive accumulation of free fatty acids (FFAs) in the liver, especially saturated FAs and their toxic metabolites, is closely related to metabolic diseases such as nonalcoholic fatty liver disease (NAFLD). Hydrogen sulfide (H2S), a novel gaseous signaling molecule, has been reported to have lipid-lowering effects, but its effect on FAs metabolism remains unclear. The purpose of this study was to investigate the effect and mechanisms of anethole dithiolethione (ADT, a sustained-release H2S donor) on hepatic FAs metabolism. ADT was administered daily for 4 weeks in male Syrian golden hamsters fed a high fat diet (HFD), and FAs profiles of liver tissues were analyzed using GC-MS. The results showed that in HFD-fed hamsters, ADT treatment significantly reduced the accumulation of saturated and monounsaturated fatty acids (C16:0, C18:0, C16:1, and C18:1n9), while increased the content of n-6 and n-3 series polyunsaturated fatty acids (C20:3n6, C20:4n6, and C22:6n3). Mechanistically, ADT obviously inhibited the overexpression of ACC1, FAS and SCD1, and up-regulated the levels of FATPs, L-FABP, CPT1α, FADS1 and FADS2. Notably, ADT evidently induced Mitofusin1 to facilitate mitochondrial fusion and optimize β-oxidation. These findings suggest that ADT plays a beneficial role by regulating the synthesis, desaturation, β-oxidation, uptake, binding/isolation, and transport of FAs. In conclusion, ADT is effective in improving liver FAs metabolic disorders and liver injuries caused by HFD.
Plant-soil nitrogen, carbon and phosphorus content after the addition of biochar, bacterial inoculums and N fertilizer
Authors: Mikajlo Irina , Pourrut Bertrand , Louvel Brice , Hynšt Jaroslav , Záhora Jaroslav 
Published: February 2020

AbstractThe use of biochar in combination with mineral or biological amendments in order to improve its influence on soil-plant properties has received growing attention. The changes of N, C and P content inLactuca sativa var. capitataaboveground plant biomass and soil after the addition of beech wood biochar combined with the addition of bacterial inoculums (Bacofil and Novarefm) and N fertilizer have been studied using spectrophotometry methods. Pots were filled with the arable soil from the plots in protection zone of water sources (Březová nad Svitavou, South Moravia, Czech Republic). Biochar with inoculums decreased plant growth in the first yield of Novaferm treatment and in both yields of Bactofil treatment. Increased plant biomass growth was observed with Novaferm addition in the second yield. Total N increase has been obtained in the plant aboveground biomass and soil of the treatments amended with inoculums and nitrogen fertilizer. The decrease of P content has been observed in plant aboveground biomass in the biochar amended samples.
Adolescent Social Isolation Reprograms the Medial Amygdala: Transcriptome and Sex Differences in Reward
Authors: Walker Deena M. , Zhou Xianxiao , Ramakrishnan Aarthi , Cates Hannah M. , Cunningham Ashley M. , Peña Catherine J. , Bagot Rosemary C. , Issler Orna , Van der Zee Yentl , Lipschultz Andrew P. , Godino Arthur , Browne Caleb J. , Hodes Georgia E. , Parise Eric M. , Torres-Berrio Angélica , Kennedy Pamela J. , Shen Li , Zhang Bin , Nestler Eric J. 
Published: February 2020

ABSTRACTAdolescence is a sensitive window for reward- and stress-associated behavior. Although stress during this period causes long-term changes in behavior in males, how females respond is relatively unknown. Here we show that social isolation stress in adolescence, but not adulthood, induces persistent but opposite effects on anxiety- and cocaine-related behaviors in male vs. female mice, and that these effects are reflected in transcriptional profiles within the adult medial amygdala (meA). By integrating differential gene expression with co-expression network analyses, we identified crystallin mu (Crym), a thyroid-binding protein, as a key driver of these transcriptional profiles. Manipulation ofCrymspecifically withinadultmeA neurons recapitulates the behavioral and transcriptional effects of social isolation and re-opens a window of plasticity that is otherwise closed. Our results establish that meA is essential for sex-specific responses to stressful and rewarding stimuli through transcriptional programming that occurs during adolescence.
Urine as a high-quality source of host genomic DNA from wild populations
Authors: Ozga Andrew T. , Webster Timothy H. , Gilby Ian C. , Wilson Melissa A. , Nockerts Rebecca S. , Wilson Michael L. , Pusey Anne E. , Li Yingying , Hahn Beatrice H. , Stone Anne C. 
Published: February 2020

AbstractThe ability to generate genomic data from wild animal populations has the potential to give unprecedented insight into the population history and dynamics of species in their natural habitats. However, in the case of many species, it is impossible legally, ethically, or logistically to obtain tissues samples of high-quality necessary for genomic analyses. In this study we evaluate the success of multiple sources of genetic material (feces, urine, dentin, and dental calculus) and several capture methods (shotgun, whole-genome, exome) in generating genome-scale data in wild eastern chimpanzees (Pan troglodytes schweinfurthii) from Gombe National Park, Tanzania. We found that urine harbors significantly more host DNA than other sources, leading to broader and deeper coverage across the genome. Urine also exhibited a lower rate of allelic dropout. We found exome sequencing to be far more successful than both shotgun sequencing and whole-genome capture at generating usable data from low-quality samples such as feces and dental calculus. These results highlight urine as a promising and untapped source of DNA that can be noninvasively collected from wild populations of many species.
Multiple timescales of neural dynamics and integration of task-relevant signals across cortex
Authors: Spitmaan Mehran , Seo Hyojung , Lee Daeyeol , Soltani Alireza 
Published: February 2020

AbstractRecent studies have proposed the orderly progression in the time constants of neural dynamics as an organizational principle of cortical computations. However, relationships between these timescales and their dependence on response properties of individual neurons are unknown. We developed a comprehensive method to simultaneously estimate multiple timescales in neuronal dynamics and integration of task-relevant signals along with selectivity to those signals. We found that most neurons exhibited multiple timescales in their response, which consistently increased from parietal to prefrontal to cingulate cortex. While predicting rates of behavioral adjustments, these timescales were not correlated across individual neurons in any cortical area, resulting in independent parallel hierarchies of timescales. Additionally, none of these timescales depended on selectivity to task-relevant signals. Our results not only suggest multiple canonical mechanisms for increasing timescales of neural dynamics across cortex but also point to additional mechanisms that allow decorrelation of these timescales to enable more flexibility.
Molecular origins of transcriptional heterogeneity in diazotrophicK. oxytoca
Authors: Bashir Tufail , Brackston Rowan D , Waite Christopher J , Kotta-Loizou Ioly , Engl Christoph , Buck Martin , Schumacher Jörg 
Published: February 2020

AbstractPhenotypic heterogeneity in clonal bacterial batch cultures is an important adaptive strategy to changing environments, including in diazotrophs with the unique capacity to convert di-nitrogen into bio-available ammonium. In diazotrophicKlebsiella oxytocawe simultaneously measured mRNA levels of key regulatory (glnK-amtB, nifLA) and structural (nifHDK) operons required for establishing nitrogen fixation, using dual molecule, single cell RNA-FISH. Through stochastic transcription models and mutual information analysis we revealed likely molecular origins for heterogeneity in nitrogenase expression. In wildtype and regulatory variant strains we inferred contributions from intrinsic and extrinsic noise, finding thatnifHDKtranscription is inherently bursty, but that noise propagation through signalling is also significant. The regulatory geneglnKhad the highest discernible effect onnifHDKvariance, while noise from factors outside of the regulatory pathway were negligible. Results provide evidence that heterogeneity is a fundamental property of this regulatory system, indicating potential constraints for engineering homogeneous nitrogenase expression.
Mutations inTAC1B: a novel genetic determinant of clinical fluconazole resistance inC. auris
Authors: Rybak Jeffrey M. , Muñoz José F. , Barker Katherine S. , Parker Josie E. , Esquivel Brooke D. , Berkow Elizabeth L. , Lockhart Shawn R. , Gade Lalitha , Palmer Glen E. , White Theodore C. , Kelly Steve L. , Cuomo Christina A. , Rogers P. David 
Published: February 2020

ABSTRACTCandida aurishas emerged as a multidrug-resistant pathogen of great clinical concern. Approximately 90% of clinicalC. aurisisolates are resistant to fluconazole, the most commonly prescribed antifungal agent, yet it remains unknown what mechanisms underpin this fluconazole resistance. To identify novel mechanisms contributing to fluconazole resistance inC. auris, the fluconazole-susceptibleC. aurisclinical isolate AR0387 was passaged in media supplemented with fluconazole to generate derivative strains which had acquired increased fluconazole resistancein vitro. Comparative analysis of comprehensive sterol profiles, [3H]-fluconazole uptake, sequencing ofC. aurisgenes homologous to genes known to contribute to fluconazole resistance in other species ofCandida, and the relative expression ofC. auris ERG11, CDR1, andMDR1were performed. All fluconazole-evolved derivative strains were found to have acquired mutations in the zinc-cluster transcription factor-encoding gene,TAC1B, and a corresponding increase inCDR1expression relative to the parental clinical isolate, AR0387. Mutations inTAC1Bwere also identified in a set of 304 globally distributedC. aurisclinical isolates representing each of the four major clades. Introduction of the most common mutation found among fluconazole-resistant clinical isolates ofC. aurisinto the fluconazole-susceptible isolate AR0387, was confirmed to increase fluconazole resistance by 8-fold, and the correction of the same mutation in a fluconazole-resistant isolate, AR0390, decreased fluconazole MIC by 16-fold. Taken together, these data demonstrate thatC. auriscan rapidly acquire resistance to fluconazolein-vitro, and that mutations inTAC1Bsignificantly contribute to clinical fluconazole resistance.IMPORTANCECandida aurisis an emerging multidrug-resistant pathogen of global concern, known to be responsible for outbreaks on six continents and commonly resistant to antifungals. While the vast majority of clinicalC. aurisisolates are highly resistant to fluconazole, an essential part of the available antifungal arsenal, very little is known about the mechanisms contributing to resistance. In this work, we show that mutations in the transcription factorTAC1Bsignificantly contribute to clinical fluconazole resistance. These studies demonstrate that mutations inTAC1Bcan arise rapidly in vitro upon exposure to fluconazole, and that a multitude of resistance-associatedTAC1Bmutations are present among the majority of fluconazole-resistantC. aurisisolates from a global collection and appear specific to a subset of lineages or clades. Thus, identification of this novel genetic determinant of resistance significantly adds to the understanding of clinical antifungal resistance inC. auris.
Elucidating the molecular interactions between uremic toxins and the Sudlow II binding site of human serum albumin
Authors: Smith Josh , Pfaendtner Jim 
Published: February 2020

AbstractProtein bound uremic toxins (PBUTs) are known to bind strongly with the primary drug carrying sites of human serum albumin (HSA), Sudlow site I and Sudlow site II. A detailed energetic and structural description of PBUT interactions with these binding sites would provide useful insight into the design of materials that specifically displace and capture PBUTs. In this work, we used molecular dynamics (MD) simulations to study in atomistic detail 4 PBUTs bound in Sudlow site II. Specifically, we used the experimentally resolved X-ray structure of simulated indoxyl sulfate (IS) bound to Sudlow site II (PBD ID: 2BXH) to generate initial binding poses for p-cresyl sulfate (pCS), indole-3-acetic acid (IAA), and hippuric acid (HA). We calculated the interaction energy between toxin and protein in MD simulations and performed mean shift clustering on the collection of molecular structures from MD to identify the primary binding modes of each toxin. We find that all 4 toxins are primarily stabilized by electrostatic interactions between their anionic moiety and the hydrophilic residues in Sudlow site II. We observed transience in the strongest toxin-protein interaction, a charge-pairing with the positively charged R410 residue. We confirm the finding that the primary binding pose of IS in Sudlow site II is stabilized by a hydrogen bond with the carbonyl oxygen of L430, and find that this is also true for IAA. We provide insight into the chemical functional groups that might be incorporated to improve the specificity of synthetic materials for PBUT capture. This work represents a next step toward the de novo design of solutions to the problem of PBUT management in CKD patients.Significance StatementIn spite of their implication in poor clinical outcomes, surprisingly little information is available about the structure and mechanisms that govern the binding of protein bound uremic toxins to their primary carrier human serum albumin. To date, only the structure of indoxyl sulfate has been determined by experiment. This paper describes a comprehensive characterization of four toxins that are known to bind Sudlow site II using molecular dynamics simulations. Based on the experimental structure of indoxyl sulfate bound to HSA, the binding mode within Sudlow site II of three additional PBUTs was determined. The structures, energetic and mechanistic analysis provide substantial new information for the nephrology community about these toxins as well as new protocols to aid future studies of PBUTs.
Differential gene expression inDrosophila melanogasterandD. nigrosparsainfected with the sameWolbachiastrain
Authors: Detcharoen Matsapume , Schilling Martin P. , Arthofer Wolfgang , Schlick-Steiner Birgit C. , Steiner Florian M. 
Published: February 2020

AbstractWolbachia, maternally inherited endosymbionts, infect nearly half of all arthropod species.Wolbachiamanipulate their hosts to maximize their transmission, but they can also provide benefits such as nutrients and resistance to viruses for their hosts. TheWolbachiastrainwMel was recently found to increase locomotor activities and possibly trigger cytoplasmic incompatibility in the flyDrosophila nigrosparsa. Here, we compared differential gene expression inDrosophila melanogaster(original host) andD. nigrosparsa(novel host), both uninfected and infected withwMel, using RNA sequencing to see if the two Drosophila species respond to the infection in the same or different ways. A total of 2164 orthologous genes were used. We found species-specific gene expression patterns. Significant changes shared by the fly species were confined to the expression of genes involved in heme binding and oxidation-reduction; the two host species differently changed the expression of genes when infected. Some of the genes were down-regulated in the infectedD. nigrosparsa, which might indicate small positive effects ofWolbachia. We discuss our findings also in the light of howWolbachiasurvive within both the native and the novel host.