bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogenomic analysis reveals the basis of adaptation of Pseudorhizobium species to extreme environments
Authors: Lassalle Florent , Dastgheib Seyed M. M. , Zhao Fang-Jie , Zhang Jun , Verbarg Susanne , Frühling Anja , Brinkmann Henner , Osborne Thomas H. , Sikorski Johannes , Balloux Francois , Didelot Xavier , Santini Joanne M. , Petersen Jörn 
Published: July 2019

AbstractThe family Rhizobiaceae includes many genera of soil bacteria, often isolated for their association with plants. Herein, we investigate the genomic diversity of a group of Rhizobium species and unclassified strains isolated from atypical environments, including seawater, rock matrix or polluted soil. Based on whole-genome similarity and core genome phylogeny, we show that this group corresponds to the genus Pseudorhizobium. We thus reclassify Rhizobium halotolerans, R. marinum, R. flavum and R. endolithicum as P. halotolerans comb. nov., P. marinum comb. nov., P. flavum comb. nov. and R. endolithicum comb. nov., respectively, and show that P. pelagicum is a synonym of P. marinum. We also delineate a new chemolithoautotroph species, P. banfieldiae sp. nov., whose type strain is NT-26T (= DSM 106348T = CFBP 8663T). This genome-based classification was supported by a chemotaxonomic comparison, with gradual taxonomic resolution provided by fatty acid, protein and metabolic profiles. In addition, we used a phylogenetic approach to infer scenarios of duplication, horizontal transfer and loss for all genes in the Pseudorhizobium pangenome. We thus identify the key functions associated with the diversification of each species and higher clades, shedding light on the mechanisms of adaptation to their respective ecological niches. Respiratory proteins acquired at the origin of Pseudorhizobium are combined with clade-specific genes to encode different strategies for detoxification and nutrition in harsh, nutrient-poor environments. Finally, we predict diagnostic phenotypes for the distinction of P. banfieldiae from other Pseudorhizobium species, including autotrophy and sensitivity to the azo dye Congo Red, which we experimentally validated.
TheDrosophilafertility factorkl-3is linked to the Y-chromosome of the vector of Chagas’ diseaseTriatoma infestans(Hemiptera: Reduviidae) and is essential for male fertility
Authors: Martins Carlos H. , da Silva Rodrigo S. V. P , Ferreira Thalia K. , Paim Rafaela , Pessoa Grasielle C. D. , Sant’Anna Mauricio V. , Gontijo Nelder F. , Araujo Ricardo N. , Pereira Marcos H. , Carvalho A. Bernardo , Koerich Leonardo B. 
Published: July 2019

AbstractIn many insects, the Y chromosome plays a key role in sexual determination and male fertility. The Chagas disease vectorTriatoma infestanshas 22 autosomal chromosomes and a pair of XY sex chromosomes. However, the knowledge on the Y chromosome of this species, its genetic content or its biological function, is very poor. Due to repetitive DNA, Y chromosome sequences are poorly assembled in genome projects, hindering structural and functional studies on Y-linked genes. Our group has developed many of the bioinformatic tools to identify Y-linked sequences in assembled genomes. Here, we describe the identification of a γ-dynein heavy chain linked to the Y-chromosome ofT. infestans. This protein is orthologous to theDrosophila melanogasterY-linked genekl-3. InD. melanogaster, dyneins of the Y chromosome are known as male fertility factors and their deletion causes male infertility. We performed knockdown of thekl-3expression to ascertain its function inT. infestans. Our results showed that injection of dsKL3 reduced, significantly, the fertility ofT. infestansmales (p<0.01). The mean number of eggs laid by the control group was 35.64 eggs/couple while the kl-3 knockdown group was of 11.82 eggs/couple (five couples did not lay any eggs). Differences in eclosion rate was even more significant, with a hatching mean rate of 16.85±10.03 and 1.69±3.58 (p<0.001) for the control and the silenced groups respectively. Our results suggest thatkl-3maintains its functional role as essential for male fertility inT. infestans. Hence, it seems that the Y-chromosome ofT. infestanshas a key role in male fertility. This is the first report of akl-3orthologue linked to the Y chromosome of an insect species outside the diptera clade. In addition to the first report of a Y-linked gene inT. infestanswith a role for male fertility, this finding is of great relevance for the study of the evolution of Y chromosomes and further studies that could lead to novel approaches in insect control.
uap: Reproducible and Robust HTS Data Analysis
Authors: Kämpf Christoph , Specht Michael , Scholz Alexander , Puppel Sven-Holger , Doose Gero , Reiche Kristin , Schor Jana , Hackermüller Jörg 
Published: July 2019

AbstractBackgroundA lack of reproducibility has been repeatedly criticized in computational research. High throughput sequencing (HTS) data analysis is a complex multi-step process. For most of the steps a range of bioinformatic tools is available and for most tools manifold parameters need to be set. Due to this complexity, HTS data analysis is particularly prone to reproducibility and consistency issues. We have defined four criteria that in our opinion ensure a minimal degree of reproducible research for HTS data analysis. A series of workflow management systems is available for assisting complex multi-step data analyses. However, to the best of our knowledge, none of the currently available work flow management systems satisfies all four criteria for reproducible HTS analysis.ResultsHere we present uap, a workflow management system dedicated to robust, consistent, and reproducible HTS data analysis. uap is optimized for the application to omics data, but can be easily extended to other complex analyses. It is available under the GNU GPL v3 license at https://github.com/yigbt/uap.Conclusionsuap is a freely available tool that enables researchers to easily adhere to reproducible research principles for HTS data analyses.
A missense variant in CREBRF is associated with taller stature in Samoans
Authors: Carlson Jenna C. , Rosenthal Samantha L. , Russell Emily M. , Hawley Nicola L. , Sun Guangyun , Cheng Hong , Naseri Take , Reupena Muagututi‘a Sefuiva , Tuitele John , Deka Ranjan , McGarvey Stephen T. , Weeks Daniel E. , Minster Ryan L. 
Published: July 2019

AbstractObjectivesStudies have demonstrated that rs373863828, a missense mutation in CREBRF, is associated with a number of anthropometric traits including body mass index (BMI), obesity, percent body fat, hip circumference, and abdominal circumference. Given the biological relationship between height and adiposity, we hypothesized that the effect of this variant on BMI might be due in part to a previously untested association of this variant with height.MethodsWe tested the hypothesis that minor allele of rs373863828 is associated with height in a Samoan population in two adult cohorts and in a separate cohort of children (age 5 - 18 years old) using linear mixed modeling.ResultsWe found evidence of a strong relationship between rs373863828 and greater mean height in Samoan adults (0.77 cm greater average height for each copy of the minor allele) with the same direction of effect in Samoan children.ConclusionsThese results suggest that the missense variant rs373863828 in CREBRF, first identified through an association with larger BMI, may be related to an underlying biological mechanism affecting overall body size including stature.
Air-interfaced colonization model suggests a commensal-like interaction ofNeisseria meningitidiswith the epithelium, which benefit from colonization byStreptococcus mitis
Authors: Audry Mathilde , Robbe-Masselot Catherine , Barnier Jean-Philippe , Gachet Benoit , Saubaméa Bruno , Schmitt Alain , Schönherr-Hellec Sophia , Léonard Renaud , Nassif Xavier , Coureuil Mathieu 
Published: July 2019

ABSTRACTNeisseria meningitidisis an inhabitant of the nasopharynx, from which it is transmitted from person to person or disseminates in the blood and becomes a harmful pathogen. In this work, we addressed the colonization of the nasopharyngeal niche by focusing on the interplay between meningococci and the mucus that lines the mucosa of the host. Using Calu-3 cells grown in air-interfaced culture, we studied the meningococcal colonization of the mucus and the host response. Our results suggested thatN. meningitidisbehaved like commensal bacteria in mucus, without interacting with human cells or actively transmigrating through the cell layer. As such, meningococci did not trigger a strong innate immune response from the Calu-3 cells. Finally, we have shown that this model is suitable for studying interaction ofN. meningitidiswith other bacteria living in the nasopharynx, and thatStreptococcus mitisbut notMoraxella catarrhaliscan promote meningococcal growth in this model.
Common neurodegeneration-associated proteins are physiologically expressed by antigen-presenting cells and are interconnected via the inflammation/autophagy-related proteins TRAF6 and SQSTM1
Authors: Nataf Serge , Guillen Marine , Pays Laurent 
Published: July 2019

ABSTRACTThere is circumstantial evidence that, under neurodegenerative conditions, peptides deriving from aggregated or misfolded specific proteins elicit adaptive immune responses. On another hand, several genes involved in familial forms of neurodegenerative diseases were found to exert key innate immune functions. However, whether or not such observations are causally linked remains unknown. To start addressing this issue, we followed a systems biology strategy based on the mining of large proteomics and immunopeptidomics databases. First, we retrieved the expression patterns of common neurodegeneration-associated proteins in two professional antigen-presenting cells, namely B-cells and dendritic cells. Surprisingly, we found that under physiological conditions, numerous neurodegeneration-associated proteins are abundantly expressed by human B-cells. A survey of the human proteome allowed us to map a unique protein-protein interaction network linking common neurodegeneration-associated proteins and their first shell interactors in human B-cells. Surprisingly, network connectivity analysis identified two major hubs that both relate with inflammation and autophagy, namely TRAF6 (TNF Receptor Associated Factor 6) and SQSTM1 (Sequestosome-1). Moreover, the mapped network in B-cells also comprised two other hub proteins involved in both inflammation and autoimmunity: HSPA8 (Heat Shock Protein Family A Member 8 also known as HSC70) and HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1). Based on these results, we then explored the Immune Epitope Database “IEDB-AR” and actually found that a large share of neurodegeneration-associated proteins were previously reported to provide endogenous MHC class II-binding peptides in human B-cells. Of note, peptides deriving from amyloid beta A4 protein, sequestosome-1 or profilin-1 were reported to bind multiple allele-specific MHC class II molecules. In contrast, peptides deriving from microtubule-associated protein tau, presenilin 2 and serine/threonine-protein kinase TBK1 were exclusively reported to bind MHC molecules encoded by the HLA-DRB1 1501 allele, a recently-identified susceptibility gene for late onset Alzheimer’s disease. Finally, we observed that the whole list of proteins reported to provide endogenous MHC class II-binding peptides in human B-cells is specifically enriched in neurodegeneration-associated proteins. Overall, our work indicates that immunization against neurodegeneration-associated proteins might be a physiological process which is shaped, at least in part, by B-cells.
Abundance, fatty acid composition and saturation index of neutral lipids are significantly different between isogenic primary and metastatic colon cancer cell lines
Authors: Munir Rimsha , Lisec Jan , Jaeger Carsten , Zaidi Nousheen 
Published: July 2019

AbstractLipid droplets, the dynamic organelles that store triglycerides (TG) and cholesterol esters (CE), are highly accumulated in colon cancer cells. This work studies the TG and CE subspecies profile in colon carcinoma cells lines, SW480 derived from primary tumor, and SW620 derived from a metastasis of the same tumor. It was previously reported that the total TG and CE content is dramatically higher in SW620 cells; however, TG and CE subspecies profile has not been investigated in detail. The presented work confirms that total TG and CE content is significantly higher in SW620 cells. Moreover, the FA-composition of TGs is significantly altered in SW620 cells, with significant decrease in the abundance of saturated triglycerides. This resulted in significantly decreased TG saturation index in SW620 cells. The saturation index of CEs was also significantly decreased in SW620 cells. The saturation indices of some other major lipid classes were either similar or only moderately different between SW480 and SW620 cells. We also compared the expression of metabolic genes that may regulate these changes in the lipidomic profiles.
An HSP90-regulated reduced-eye phenotype in Tribolium shows fitness benefits and thus provides evidence for evolutionary capacitance
Authors: Aboelsoud Rasha , Kurtz Joachim 
Published: July 2019

AbstractEvolution relies on genetic variation as the raw material for adaptation. The release of cryptic genetic variation (CGV), which can be regulated by the evolutionary capacitor heat shock protein 90 (HSP90), may thus be important for rapid adaptation. However, the fitness benefits of HSP90-regulated phenotypes are still under debate. Here, we show in the important model insect Tribolium castaneum that HSP90 impairment by two independent methods, RNA interference and chemical inhibition, revealed the same reduced-eye phenotype, which was stably inherited without further HSP90 inhibition. The penetrance and fitness of this trait increased under ambient light stress. This is the first demonstration that a phenotype released through HSP90 inhibition can be adaptive.
A novel multidimensional reinforcement task in mice elucidates sex-specific behavioral strategies
Authors: Kutlu Munir Gunes , Zachry Jennifer E , Brady Lillian J , Melugin Patrick R , Sanders Christina , Tat Jennifer , Johnson Amy R , Thibeault Kimberly , Lopez Alberto J. , Calipari Erin S. 
Published: July 2019

AbstractBackgroundSex is a critical biological variable in the neuropathology of psychiatric disease, and in many cases, women represent a vulnerable population. It has been hypothesized that sex differences in neuropsychiatric disorders are manifestations of differences in basic reward processing. However, preclinical models often present rewards in isolation, ignoring that ethologically, reward seeking requires the consideration of potential aversive outcomes.MethodsWe developed a Multidimensional Cue Outcome Action Task (MCOAT) to dissociate motivated action from cue learning and valence. Mice are trained in a series of operant tasks. In phase 1, mice acquire positive and negative reinforcement in the presence of discrete discriminative stimuli. In phase 2, both discriminative stimuli are presented concurrently allowing us to parse innate behavioral strategies based on reward seeking and shock avoidance. Phase 3 is punished responding where a discriminative stimulus predicts that nose-poking for sucrose occurs concurrently with footshock, allowing for the assessment of how positive and negative outcomes are relatively valued.ResultsFemales prioritize avoidance of negative outcomes over seeking positive, while males have the opposite strategy. In cases where rules are uncertain, males and females employ different strategies, with females demonstrating bias for shock avoidance.ConclusionsThe MCOAT has broad utility for neuroscience research where pairing this task with recording and manipulation techniques will allow for the definition of the discrete information encoded within cellular populations. Ultimately, we show that making conclusions from unidimensional data leads to inaccurate generalizations about sex-specific behaviors that do not accurately represent ground truth.
Metabolic signature in nucleus accumbens for anti-depressant-like effects of acetyl-L-carnitine: Anin vivo1H-magnetic resonance spectroscopy study at 14 T
Authors: Cherix Antoine , Larrieu Thomas , Grosse Jocelyn , Rodrigues João , McEwen Bruce , Nasca Carla , Gruetter Rolf , Sandi Carmen 
Published: July 2019

AbstractBackgroundEmerging evidence suggests that hierarchical status may provide vulnerability to develop stress-induced depression. Energy metabolism in the nucleus accumbens (NAc) was recently related to hierarchical status and vulnerability to develop depression-like behavior. Acetyl-L-carnitine (LAC), a mitochondria-boosting supplement, has shown promising antidepressant-like effects opening promising therapeutic strategies for restoring energy balance in depressed patients. Here, we investigated the metabolic impact in the NAc of antidepressant LAC treatment in chronically stressed mice.MethodMice were characterized for emotional behaviors and social rank. They were then exposed to chronic restraint stress (CRS) for 21 days and subsequently tested in a social behavior (SB) test. A group of mice was also given LAC supplementation during the 7 last CRS days. Mice were then tested in the SB and forced swim tests (FST) and scannedin vivousing1H-magnetic resonance spectroscopy (1H-MRS) to quantitatively assess the NAc neurochemical profile.ResultsDominant, but not subordinate, mice showed behavioral vulnerability to CRS. In the NAc, dominant mice showed reduced levels of several energy-related metabolites. LAC treatment counteracted stress-induced behavioral changes in dominant mice, and normalized levels of taurine, phosphocreatine, glutamine and phosphocholine in the NAc. No major accumbal metabolic changes were observed in subordinate mice.ConclusionHigh social rank is confirmed as a vulnerability factor to develop chronic stress-induced depressive-like behaviors. We reveal a metabolic signature in the NAc for the antidepressant-like effects of LAC in vulnerable mice, characterized by restoration of stress-induced alterations in neuroenergetics and lipid function.
Isolation of muscle stem cells from rat skeletal muscles
Authors: Sesillo Francesca Boscolo , Wong Michelle , Cortez Amy , Alperin Marianna 
Published: July 2019

ABSTRACTBackgroundMuscle stem cells (MuSCs) are involved in homeostatic maintenance of skeletal muscles and play a central role in muscle regeneration in response to injury. Thus, understanding MuSC autonomous properties is of fundamental importance for studies of muscle degenerative diseases and muscle plasticity. Rat, as an animal model, has been widely used in the skeletal muscle field, however an efficient approach for MuSC isolation through fluorescence-activated cell sorting from rat muscles has never been described. This work aims to develop and validate an effective protocol for MuSC isolation from rat skeletal muscles.MethodsTibialis anterior, gastrocnemius, diaphragm, and the individual components of the pelvic floor muscle complex (coccygeus, iliocaudalis, and pubocaudalis) were harvested from female rats and digested for isolation of MuSCs. Three protocols, employing different cell surface markers (CD106, CD56, and CD29), were compared for their ability to isolate a pure MuSC population.ResultsCells obtained using the protocol that relies only on VCAM-1 (CD106) as a positive marker showed high expression of Pax7 upon isolation, ability to progress through myogenic lineage while in culture, and complete differentiation in serum deprived conditions. The protocol was further validated in other skeletal muscles proving to be reproducible.ConclusionsCD106 is an efficient marker for reliable isolation of MuSCs from a variety of rat skeletal muscles.
Temporal and spatiotemporal perturbations in paced finger tapping point to a common mechanism for the processing of time errors
Authors: López Sabrina L. , Laje Rodrigo 
Published: July 2019

AbstractPaced finger tapping is a sensorimotor synchronization task where a subject is instructed to keep pace with an external metronome, as when following along with the beat of music, and the time differences (asynchronies) between each stimulus and its response are recorded. The usual way to study the underlying error correction mechanism is to make unexpected temporal perturbations to the stimuli sequence and then let the subject recover average synchronization. A critical but overlooked issue in traditional temporal perturbations, however, is that at the moment of perturbation two things change: both the stimuli period (a parameter) and the asynchrony (a variable). In terms of experimental manipulation, it would be desirable to have separate, independent control of parameter and variable values. In this work we perform paced finger tapping experiments combining simple temporal perturbations (tempo step change) and spatial perturbations with temporal effect (raised or lowered point of contact). In this way we decouple the parameter-and-variable confounding of traditional temporal perturbations and perform novel perturbations where either the parameter only changes or the variable only changes. Our results show nonlinear features like asymmetry and are compatible with the idea of a common mechanism for the correction of all types of asynchronies. We suggest taking this confounding into account when analyzing perturbations of any kind in finger tapping tasks but also in other areas of sensorimotor synchronization, like music performance experiments and paced walking in gait coordination studies.
Identification of activators of human fumarate hydratase by quantitative high-throughput screening
Authors: Zhu Hu , Lee Olivia W. , Shah Pranav , Jadhav Ajit , Xu Xin , Patnaik Samarjit , Shen Min , Hall Matthew D. 
Published: July 2019

AbstractFumarate hydratase (FH) is a metabolic enzyme that is part of the Krebs-cycle, and reversibly catalyzes the hydration of fumarate to malate. Mutations of the FH gene have been associated with fumarate hydratase deficiency (FHD), hereditary leiomyomatosis, renal cell cancer (HLRCC), and other diseases. Currently there are no high-quality small molecule probes for studying human fumarate hydratase. To address this, we developed a quantitative high throughput screening (qHTS) FH assay and screened a total of 57,037 compounds from in-house libraries in dose-response. While no inhibitors of FH were confirmed, a series of phenyl-pyrrolo-pyrimidine-diones were identified as activators of human fumarate hydratase. These compounds were not substrates of fumarate hydratase, were inactive in a malate dehydrogenase counter screen, and showed no detectable reduction–oxidation activity. The binding of two compounds from the series to human fumarate hydratase was confirmed by microscale thermophoresis. The low hit rate in this screening campaign confirmed that FH is a ‘tough target’ to modulate, and the small molecule activators of human fumarate hydratase reported here may serve as a starting point for further optimization and development into cellular probes of human FH and potential drug candidates.