bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular mechanism of sulfur chemolithotrophy in the betaproteobacterium Pusillimonas ginsengisoli
Authors: Mandal Subhrangshu , Rameez Moidu Jameela , Pyne Prosenjit , Bhattacharya Sabyasachi , Sarkar Jagannath , Ghosh Wriddhiman 
Published: July 2019

AbstractMolecular mechanism of chemolithotrophic sulfur oxidation in Betaproteobacteria is less explored than that in Alphaproteobacteria. Here we carried out whole genome sequencing and analysis of a new betaproteobacterial isolate Pusillimonas ginsengisoli SBSA which oxidizes thiosulfate via formation tetrathionate as an intermediate. The 4.7-Mb SBSA genome was found to encompass a complete soxCDYZAXOB operon, plus one thiosulfate dehydrogenase (tsdA) and sulfite:acceptor oxidoreductase (sorAB) genes. Recombination-based knock-out of tsdA revealed that the entire thiosulfate oxidized by SBSA is first converted to tetrathionate, and no thiosulfate is directly converted to sulfate as typical of the Alphaproteobacterial Sox pathway whereas its tetrathionate-oxidizing ability was as good as that of the wild-type. The ∆soxYZ knock-out mutant exhibited wild-type-like phenotype for thiosulfate/tetrathionate oxidation, whereas ∆soxB oxidized thiosulfate only up to tetrathionate and had complete impairment of tetrathionate oxidation. However, substrate-dependent O2-consumption rate of whole cells, and sulfur-oxidizing enzyme activities of cell-free extracts, measured in the presence/absence of thiol-inhibitors/glutathione, indicated that glutathione plays a key role in SBSA tetrathionate oxidation. All the present findings collectively indicated that glutathione:tetrathionate coupling in Pusillimonas ginsengisoli may involve some unknown proteins other than thiol dehydrotransferase(ThdT), while subsequent oxidation of the potential glutathione:sulfodisulfane and sulfite molecules produced may proceed via soxBCD action.
Negative plant-microbiome feedback limits productivity in aquaponics
Authors: Day Jessica A. , Otwell Anne E. , Diener Christian , Tams Kourtney E. , Bebout Brad , Detweiler Angela M. , Lee Michael D. , Scott Madeline T. , Ta Wilson , Ha Monica , Carreon Shienna A. , Tong Kenny , Ali Abdirizak A. , Gibbons Sean M. , Baliga Nitin S. 
Published: July 2019

AbstractThe demand for food will outpace productivity of conventional agriculture due to projected growth of the human population, concomitant with shrinkage of arable land, increasing scarcity of freshwater, and a rapidly changing climate. Efforts to increase conventional agricultural output come with significant environmental impacts stemming from deforestation and excessive use of chemicals, including soil salinization, erosion, and nutrient runoffs. While aquaponics has potential to sustainably supplement food production with minimal environmental impact, there is a need to better characterize the complex interplay between the various components (fish, plant, microbiome) of these systems to optimize scale up and productivity. For instance, much of our knowledge of beneficial and detrimental microbial communities vis-à-vis crop productivity comes from studies on plant-microbiome interactions in soil. Here, we investigated how the practice of continued transfer of microbial communities from pre-existing systems might promote or impede productivity of aquaponics. Specifically, we monitored plant growth phenotypes, water chemistry, and microbiome composition of rhizospheres, biofilters, and fish feces over 61-days of lettuce (Lactuca sativa) growth in aquaponic systems inoculated with bacteria that were either commercially sourced or originating from a pre-existing aquaponic system. Strikingly, L. sativa plant and root growth was significantly reduced across all replicates inoculated with the established microbiome. Further analyses revealed the reduced productivity was potentially a consequence of plant-specific pathogen enrichment, including Pseudomonas, through transfer of microbiomes from pre-existing systems – a phenomenon consistent with negative feedbacks in soil ecology. These findings underscore the need for diagnostic tools to monitor microbiome composition, detect negative feedbacks early, and minimize pathogen accumulation in aquaponic systems.
Innovations in Primate Interneuron Repertoire
Authors: Krienen Fenna M. , Goldman Melissa , Zhang Qiangge , del Rosario Ricardo , Florio Marta , Machold Robert , Saunders Arpiar , Levandowski Kirsten , Zaniewski Heather , Schuman Benjamin , Wu Carolyn , Lutservitz Alyssa , Mullally Christopher D. , Reed Nora , Bien Elizabeth , Bortolin Laura , Fernandez-Otero Marian , Lin Jessica , Wysoker Alec , Nemesh James , Kulp David , Burns Monika , Tkachev Victor , Smith Richard , Walsh Christopher A. , Dimidschstein Jordane , Rudy Bernardo , Kean Leslie , Berretta Sabina , Fishell Gord , Feng Guoping , McCarroll Steven A. 
Published: July 2019

ABSTRACTPrimates and rodents, which descended from a common ancestor more than 90 million years ago, exhibit profound differences in behavior and cognitive capacity. Modifications, specializations, and innovations to brain cell types may have occurred along each lineage. We used Drop-seq to profile RNA expression in more than 184,000 individual telencephalic interneurons from humans, macaques, marmosets, and mice. Conserved interneuron types varied significantly in abundance and RNA expression between mice and primates, but varied much more modestly among primates. In adult primates, the expression patterns of dozens of genes exhibited spatial expression gradients among neocortical interneurons, suggesting that adult neocortical interneurons are imprinted by their local cortical context. In addition, we found that an interneuron type previously associated with the mouse hippocampus—the “ivy cell”, which has neurogliaform characteristics—has become abundant across the neocortex of humans, macaques, and marmosets. The most striking innovation was subcortical: we identified an abundant striatal interneuron type in primates that had no molecularly homologous cell population in mouse striatum, cortex, thalamus, or hippocampus. These interneurons, which expressed a unique combination of transcription factors, receptors, and neuropeptides, including the neuropeptide TAC3, constituted almost 30% of striatal interneurons in marmosets and humans. Understanding how gene and cell-type attributes changed or persisted over the evolutionary divergence of primates and rodents will guide the choice of models for human brain disorders and mutations and help to identify the cellular substrates of expanded cognition in humans and other primates.
Hydrogen peroxide as regeneration-initiation signal that activates pERK to trigger planarian regeneration
Authors: Jaenen Vincent , Fraguas Susanna , Bijnens Karolien , Vaca Mireia , Artois Tom , Romero Rafael , Smeets Karen , Cebrià Francesc 
Published: July 2019

AbstractDespite the extensive research on molecular pathways controlling the process of regeneration in planarians and other regeneration models, little is known about the actual initiation signals necessary to induce regeneration. Previously the involvement of ROS, EGFR and MAPK/ERK has been demonstrated during planarian regeneration, however the exact interplay has not been yet described. By selectively interfering with major mediators in all three key parts (ROS, EGFR & MAPK/ERK), we were able to identify amputation/wound-induced ROS, and H2O2specifically, as upstream cue in activating regeneration-initiation. In addition, our results demonstrate new relationships between regeneration related ROS production and MAPK/ERK activation at early regeneration stages, as well as the involvement of the EGFR-signaling pathway. In summary, our results suggest a new and more extensive signaling model with ROS, and H2O2, highlighted as upstream initiation-factor and its important functions in the downstream EGFR-MAPK/ERK pathway during planarian regeneration.
Continuous transcription initiation guarantees robust repair of transcribed genes and regulatory regions in response to DNA damage
Authors: Liakos Anastasios , Konstantopoulos Dimitris , Lavigne Matthieu D. , Fousteri Maria 
Published: July 2019

ABSTRACTInhibition of RNA synthesis caused by DNA damage-impaired RNA polymerase II (Pol II) elongation is found to conceal a local increase inde novotranscription, slowly progressing from Transcription Start Sites (TSSs) to gene ends. Although associated with accelerated repair of Pol II-encountered lesions and limited mutagenesis, it is still unclear how this mechanism is maintained during recovery from genotoxic stress. Here we uncover a surprising widespread gain in chromatin accessibility and preservation of the active histone mark H3K27ac after UV-irradiation. We show that the concomitant increase in Pol II release from promoter-proximal pause (PPP) sites of most active genes, PROMoter uPstream Transcripts (PROMPTs) and enhancer RNAs (eRNAs) favors unrestrained initiation, as demonstrated by the synthesis of short nascent RNAs, including TSS-associated RNAs (start-RNAs). In accordance, drug-inhibition of the transition into elongation replenished the post-UV reduced levels of pre-initiating pol II at TSSs. Continuous engagement of new Pol II thus ensures maximal transcription-driven DNA repair of active genes and non-coding regulatory loci. Together, our results reveal an unanticipated layer regulating the UV-triggered transcriptional-response and provide physiologically relevant traction to the emerging concept that transcription initiation rate is determined by pol II pause-release dynamics.
Regulation of thymocyte β-selection, development and positive selection by glycogen synthase kinase-3
Authors: Parsons Michael J. , Patel Satish , Doble Bradley W. , Ohashi Pamela S. , Woodgett James R. 
Published: July 2019

AbstractGlycogen synthase kinase-3 (GSK-3) is a ubiquitously expressed serine/threonine kinase, that exists as two isoforms in mammals, GSK-3α and GSK-3β, that are key downstream mediators of the phosphatidylinositol 3’ kinase, Wnt, Notch and other pathways. Here, we report that simultaneous inactivation of both GSK-3α and GSK-3β during early thymocyte ontogeny has profound effects on both β-selection and positive selection, key checkpoints essential to producing functionally mature αβ T cells. Conditional GSK-3α/β knockout animals (LckCre+ GSK-3αβfl/fl) possessed pre-double positive (pre-DP) thymocytes (CD4−CD8−CD117−CD25−) with compromised TCRβ chain expression along with elevated levels of β-catenin and reduced Notch activity. β-selection was impaired allowing pre-DP thymocytes to differentiate to DP thymocytes (CD4+CD8+) while bypassing strict requirements for productive TCRβ chain rearrangements and functional expression. Also impaired was the requisite pre-TCR and Notch-mediated expansion that normally precedes differentiation to the DP stage. Consequently, LckCre+ GSK-3αβfl/fl mice initially generated fewer DP thymocytes that expressed significantly reduced levels of mature TCR. The aberrant DP thymocytes expressed high levels of the pro-survival Bcl-2 family member Mcl-1, failed positive selection and accumulated as CD4hiCD8lo positive selection intermediates resulting in loss of both mature CD4 and CD8 lineages. LckCre+ GSK-3αβfl/fl mice succumbed to oligoclonal peripheral lymphomas with high penetrance. These data reveal essential roles for GSK-3 in several checkpoints of early T cell development.
Parameters and determinants of responses to selection in antibody libraries
Authors: Schulz Steven , Boyer Sébastien , Smerlak Matteo , Cocco Simona , Monasson Rémi , Nizak Clément , Rivoire Olivier 
Published: July 2019

AbstractAntibody repertoires contain binders to nearly any target antigen. The sequences of these antibodies differ mostly at few sites located on the surface of a scaffold that itself consists of much less varied amino acids. What is the impact of this scaffold on the response to selection of a repertoire? To gauge this impact, we carried out quantitative phage display experiments with three antibody libraries based on distinct scaffolds harboring the same diversity at randomized sites, which we selected for binding to four arbitrary targets. We first show that the response to selection of an antibody library is captured by a simple and measurable parameter with direct physical and information-theoretic interpretations. Second, we identify a major determinant of this parameter which is encoded in the scaffold, its degree of evolutionary maturation. Antibodies undergo an accelerated evolutionary process, called affinity maturation, to improve their affinity to a given target antigen as part of the adaptive immune response. We find that libraries of antibodies built around such maturated scaffolds have a lower response to selection to other arbitrary targets than libraries built around naïve scaffolds of germline origin. Our results are a first step towards quantifying and controlling the evolutionary potential of biomolecules.
Diurnal variation in xylem water isotopic signature biases depth of root-water uptake estimates
Authors: De Deurwaerder Hannes , Visser Marco D. , Detto Matteo , Boeckx Pascal , Meunier Félicien , Zhao Liangju , Wang Lixin , Verbeeck Hans 
Published: July 2019

SummaryStable water isotopes are a powerful and widely used tool to derive the depth of root water uptake (RWU) in lignified plants. Uniform xylem water isotopic signature (i-H2O-xyl) along the length of a lignified plant is a central assumption, which has never been properly evaluated.Here we studied the effects of diurnal variation in RWU, sap flow velocity and various other soil and plant parameters oni-H2O-xylsignature within a plant using a mechanistic plant hydraulic model.Our model predicts significant variation ini-H2O-xylalong the full length of an individual plant arising from diurnal RWU fluctuations and vertical soil water heterogeneity. Moreover, significant differences ini-H2O-xylemerge between individuals with different sap flow velocities. We corroborated our model predictions with field observations from French Guiana and northwestern China. Modelledi-H2O-xylvaried considerably along stem length ranging up to 18.3‰ in δ2H and 2.2‰ in δ18O, largely exceeding the range of measurement error.Our results show clear violation of the fundamental assumption of uniformi-H2O-xyland occurrence of significant biases when using stable isotopes to assess RWU. As a solution, we propose to include monitoring of sap flow and soil water potential for more robust RWU depth estimates.
In vivo characterization of neurophysiological diversity in the lateral supramammillary nucleus during hippocampal sharp-wave ripples of adult rats
Authors: Vicente Ana F , Slézia Andrea , Ghestem Antoine , Bernard Christophe , Quilichini Pascale P 
Published: July 2019

AbstractThe extent of the networks that control the genesis and modulation of hippocampal sharp wave ripples (SPW-Rs), which are involved in memory consolidation, remains incompletely understood. Here, we performed a detailed in vivo analysis of single cell firing in the lateral supramammillary nucleus (lSuM) during theta and slow oscillations, including SPW-Rs, in anesthetized rats. We classified neurons as SPW-R-active and SPW-R unchanged according to whether or not they increased their firing during SPW-Rs. We show that lSuM SPW-R-active neurons increase their firing prior SPW-Rs peak power and prior hippocampal pyramidal cell activation. Moreover, lSuM SPW-R-active neurons show increased firing activity during theta and slow oscillations as compared to unchanged-neurons. SPW-R-active neurons are more active during high peak power SPW-Rs, whereas SPW-R-unchanged neurons are more active during long SPW-Rs. These results suggest that a sub-population of lSuM neurons can interact with the hippocampus during SPW-Rs, raising the possibility that the lSuM may modulate memory consolidation.
Genome-scale profiling reveals higher proportions of phylogenetic signal in non-coding data
Authors: Literman Robert , Schwartz Rachel S. 
Published: July 2019

AbstractAccurate estimates of species relationships are integral to our understanding of evolution, yet many relationships remain controversial despite whole-genome sequence data. These controversies are due in part to complex patterns of phylogenetic and non-phylogenetic signal coming from regions of the genome experiencing distinct evolutionary forces, which can be difficult to disentangle. Here we profile the amounts and proportions of phylogenetic and non-phylogenetic signal derived from loci spread across mammalian genomes. We identified orthologous sequences from primates, rodents, and pecora, annotated sites as one or more of nine locus types (e.g. coding, intronic, intergenic), and profiled the phylogenetic information contained within locus types across evolutionary timescales associated with each clade. In all cases, non-coding loci provided more overall signal and a higher proportion of phylogenetic signal compared to coding loci. This suggests potential benefits of shifting away from primarily targeting genes or coding regions for phylogenetic studies, particularly in this era of accessible whole genome sequence data. In contrast to long-held assumptions about the phylogenetic utility of more variable genomic regions, most locus types provided relatively consistent phylogenetic information across timescales, although we find evidence that coding and intronic regions may, respectively and to a limited degree, inform disproportionately about older and younger splits. As part of this work we also validate the SISRS pipeline as an annotation-free ortholog discovery pipeline capable of identifying millions of phylogenetically informative sites directly from raw sequencing reads.
Neural systems for memory-based value judgment and decision-making
Authors: Vaidya Avinash R. , Badre David 
Published: July 2019

AbstractReal life choices often require that we draw inferences about the value of options based on structured, schematic knowledge about their utility for our current goals. Other times, value information may be retrieved directly from a specific prior experience with an option. In a functional magnetic resonance imaging (fMRI) experiment, we investigated the neural systems involved in retrieving and assessing information from different memory sources to support value-based choice. Participants completed a task in which items could be conferred positive or negative value based on schematic associations (i.e. schema value), or learned directly from experience via deterministic feedback (i.e. experienced value). We found that ventromedial prefrontal cortex (vmPFC) activity correlated with the influence of both experience- and schema-based values on participants’ decisions. Connectivity between vmPFC and middle temporal cortex also tracked the inferred value of items based on schematic associations on the first presentation of ingredients, prior to any feedback. In contrast, the striatum responded to participants’ willingness to bet on ingredients as a function of the unsigned strength of their memory for those options’ values. These results argue that striatum and vmPFC play distinct roles in memory-based value judgment and decision-making. Specifically, the vmPFC assesses the value of options based on information inferred from schematic knowledge and retrieved from prior direct experience, while the striatum controls a decision to act on options based on memory strength.
Global analysis of protein degradation in prion infected cells
Authors: Hutti Charles , Welle Kevin A. , Hryhorenko Jennifer R. , Ghaemmaghami Sina 
Published: July 2019

ABSTRACTPrion diseases are rare neurological disorders caused by the misfolding of the cellular prion protein (PrPC) into cytotoxic fibrils (PrPSc). Intracellular PrPScaggregates primarily accumulate within late endosomes and lysosomes, organelles that participate in the degradation and turnover of a large subset of the proteome. Thus, intracellular accumulation of PrPScaggregates have the potential to globally influence protein degradation kinetics within an infected cell. We analyzed the proteome-wide effect of prion infection on protein degradation rates in N2a neuroblastoma cells by dynamic stable isotopic labeling with amino acids in cell culture (dSILAC) and bottom-up proteomics. The analysis quantified the degradation rates of more than 4,700 proteins in prion-infected and uninfected cells. As expected, the degradation rate of the prion protein is significantly decreased upon aggregation in infected cells. In contrast, the degradation kinetics of the remainder of the N2a proteome generally increases upon prion infection. This effect occurs concurrently with increases in the cellular activities of autophagy and lysosomal hydrolases. The resulting enhancement in proteome flux may play a role in the survival of N2a cells upon prion infection.
Differentiation of Pluripotent Synthetic Minimal Cells via Genetic Circuits and Programmable Mating
Authors: Gaut Nathaniel J. , Gomez-Garcia Jose , Heili Joseph M. , Cash Brock , Han Qiyuan , Engelhart Aaron E. , Adamala Katarzyna P. 
Published: July 2019

AbstractSynthetic minimal cells, here defined as liposomal bioreactors synthesizing protein, are a recent technology that models the intricate gene and protein networks of live cells, without the noise inherent to natural systems. Here we show a toolset for engineering combinatorial genetic circuits in synthetic cells, where distinct populations of synthetic cells control single-gene components, and those populations are assembled via programmable fusion to construct complex biological pathways. We utilize this technology to demonstrate that progenitor populations can mimic differentiation into new lineages in response to small molecule stimuli or as an effect of “mating” with another synthetic cell population. This provides a practical tool for metabolic engineering and natural pathway study, as well as paving the way towards the construction of live synthetic cells with complex gene pathways and the ability to form distinct lineages.
SCelVis: Powerful explorative single cell data analysis on the desktop and in the cloud
Authors: Obermayer Benedikt , Holtgrewe Manuel , Nieminen Mikko , Messerschmidt Clemens , Beule Dieter 
Published: July 2019

AbstractBackgroundSingle cell omics technologies present unique opportunities for biomedical and life sciences from lab to clinic, but the high dimensional nature of such data poses challenges for computational analysis and interpretation. Furthermore, FAIR data management as well as data privacy and security become crucial when working with clinical data, especially in cross-institutional and translational settings. Existing solutions are either bound to the desktop of one researcher or come with dependencies on vendor-specific technology for cloud storage or user authentication.ResultsTo facilitate analysis and interpretation of single-cell data by users without bioinformatics expertise, we present SCelVis, a flexible, interactive and user-friendly app for web-based visualization of pre-processed single-cell data. Users can survey multiple interactive visualizations of their single cell expression data and cell annotation, and download raw or processed data for further offline analysis. SCelVis can be run both on the desktop and cloud systems, accepts input from local and various remote sources using standard and open protocols, and allows for hosting data in the cloud and locally.MethodsSCelVis is implemented in Python using Dash by Plotly. It is available as a standalone application as a Python package, via Conda/Bioconda and as a Docker image. All components are available as open source under the permissive MIT license and are based on open standards and interfaces, enabling further development and integration with third party pipelines and analysis components. The GitHub repository is https://github.com/bihealth/scelvis.