bluuebunny/crossref_metadata_2025_split huggingface dataset:
Press disturbance unveils different community structure, function and assembly of bacterial taxa and functional genes in mesocosm-scale bioreactors
Authors: Santillan E. , Constancias F. , Wuertz S. 
Published: October 2019

AbstractSustained perturbations, or press disturbances, are of interest in microbial ecology as they can drive systems to alternative stable states. Here, we tested the effect of a sustained doubling of organic carbon loading on structure, assembly and function of bacterial communities. Two sets of replicate 5-liter sequencing batch reactors were operated at two different organic carbon loading levels (323 and 629 mg COD L-1) for a period of 74 days, following 53 days of acclimation after inoculation with sludge from a full-scale treatment plant. Temporal dynamics of community taxonomic and functional gene structure were derived from metagenomics and 16S rRNA gene metabarcoding data. Assembly mechanisms were assessed through a mathematical null model on the effective bacterial turnover expressed as a proportion of total bacterial diversity. Disturbed reactors exhibited different community function, structure and assembly compared to the undisturbed reactors. Bacterial taxa and functional genes showed dissimilar alpha-diversity and community assembly patterns. Deterministic assembly mechanisms were generally stronger in disturbed reactors, associated with common taxa. Stochastic assembly was more important for functional genes and was driven by rare genes. We urge caution when assessing microbial community assembly mechanisms, as results can vary depending on the approach.
How beat perception coopts motor neurophysiology
Authors: Cannon Jonathan J. , Patel Aniruddh D. 
Published: October 2019

AbstractBeat perception is central to music cognition. The motor system is involved in beat perception, even in the absence of movement, yet current frameworks for modeling beat perception do not strongly engage with the motor system’s neurocomputational properties. We believe fundamental progress on modeling beat perception requires a synthesis between cognitive science and motor neuroscience, yielding predictions to guide research. Success on this front would be a landmark in the study of how “embodied cognition” is implemented in brain activity. We illustrate this approach by proposing specific roles for two key motor brain structures (the supplementary motor area, and the dorsal striatum of the basal ganglia) in covert beat maintenance, building on current research on their role in actual movement.Highlights⍰Components of the brain’s motor system are activated by the perception of a musical beat, even in the absence of movement, and may play an important role in beat-based temporal prediction.⍰Two key brain regions involved in movement, the supplementary motor area and dorsal striatum, have neurocomputational properties that lend themselves to beat perception.⍰In supplementary motor area, neural firing rates represent the phase of cyclic sensorimotor processes.⍰Supplementary motor area’s involvement in perceptual suppression of self-generated sounds suggests that it could play a broader role in informing auditory expectations.⍰Dorsal striatum plays a central role in initiating and sequencing units of movement, and may serve similar functions in structuring beat-based temporal anticipation.
A simple mass-action model predicts genome-wide protein timecourses from mRNA trajectories during a dynamic response in two strains ofSaccharomyces cerevisiae
Authors: Kuo Sidney , Egertson Jarrett D. , Merrihew Gennifer E. , MacCoss Michael J. , Pollard Daniel A. , Rifkin Scott A. 
Published: October 2019

AbstractAlthough mRNA is a necessary precursor to protein, several studies have argued that the relationship between mRNA and protein levels is often weak. This claim undermines the functional relevance of conclusions based on quantitative analyses of mRNA levels, which are ubiquitous in modern biology from the single gene to the whole genome scale. Furthermore, if post-translational processes vary between strains and species, then comparative studies based on mRNA alone would miss an important driver of diversity. However, gene expression is dynamic, and most studies examining relationship between mRNA and protein levels at the genome scale have analyzed single timepoints. We measure yeast gene expression after pheromone exposure and show that, for most genes, protein timecourses can be predicted from mRNA timecourses through a simple, gene-specific, generative model. By comparing model parameters and predictions between strains, we find that while mRNA variation often leads to protein differences, evolution also manipulates protein-specific processes to amplify or buffer transcriptional regulation.
Dopamine and risky decision-making in pathological and problem gamblers
Authors: Peters Jan , Vega Taylor , Weinstein Dawn , Mitchell Jennifer , Kayser Andrew 
Published: October 2019

AbstractGambling disorder is a behavioral addiction that is associated with impairments in value-based decision-making such as increased temporal discounting and reduced risk-aversion. Dopamine regulates learning and decision-making by modulating information processing throughout fronto-striatal circuits. Although the role of alterations in dopamine neurotransmission in the etiology of gambling disorder is controversial, preliminary evidence suggests that specifically increasing frontal dopamine levels might improve cognitive functioning in pathological and problem gamblers. We therefore examined whether increasing frontal dopamine levels via the catechol-O-methyltransferase (COMT) inhibitor tolcapone would reduce risky choice in a group of pathological and problem gamblers (n=14) in a repeated-measures counter-balanced placebo-controlled double-blind study. Choice data were fit using hierarchical Bayesian parameter estimation and a modeling scheme that combined a risky choice model with the drift diffusion model to account for both choices and response time distributions. Model comparison revealed that the data were best accounted for by a variant of the drift diffusion model with a non-linear modulation of trial-wise drift rates by value differences, confirming recent findings. Contrary to our hypothesis, risk-taking was slightly increased under tolcapone vs. placebo (Cohen’s d= −.281). Examination of drug effects on diffusion model parameters revealed an increase in the value-dependency of the drift rate (Cohen’s d= .932) with a simultaneous reduction in the maximum drift rate (Cohen’s d= −1.84). These results add to previous work on the potential role of COMT inhibitors in behavioral addictions, and show no consistent beneficial effect of tolcapone on risky choice in gambling disorder. Modeling results add to mounting evidence for the applicability of diffusion models in value-based decision-making. Future work should focus on individual genetic, clinical and cognitive factors that might account for the heterogeneity in the effects of COMT inhibition.
Reference transcriptome data in silkwormBombyx mori
Authors: Yokoi Kakeru , Tsubota Takuya , Jouraku Akiya , Sezutsu Hideki , Bono Hidemasa 
Published: October 2019

AbstractBackgroundThe silkwormBombyx moriis a lepidopteran model insect with biological and industrial importance. Its high-quality genome sequence has recently become available and the utilization of this information in combination with extensive transcriptomic analyses is expected to provide an elaborate gene model. It will also be possible to clarify gene expression in detail using this approach.ResultsWe herein performed RNA-seq analysis of ten major tissues/subparts of silkworm larvae. Sequences were mapped onto the reference genome assembly and reference transcriptome data was successfully constructed. The reference data provided a nearly complete sequence forsericin-1, a major silk gene with a complex structure. We also markedly improved the gene model for other genes. Transcriptomic expression was investigated in each tissue and a number of transcripts were identified that were exclusively expressed in tissues such as the testis. Transcripts strongly expressed in the midgut formed tight genomic clusters, suggesting that they originated from tandem gene duplication. Transcriptional factor genes expressed in specific tissues or the silk gland subparts were also identified.ConclusionsWe successfully constructed reference transcriptome data in the silkworm and found that a number of transcripts showed unique expression profiles. These results will facilitate basic studies on the silkworm and accelerate its applications, which will contribute to further advances in lepidopteran and entomological research and the practical use of these insects.
Anatomically remote education of B cells is required for colonic health
Authors: Surana Neeraj K. , Couter Cheryn J. , Alvarez David , von Andrian Uli H. , Kasper Dennis L. 
Published: October 2019

AbstractMucosa-associated lymphoid tissues contain roughly 80% of all immune cells and produce virtually all of the body’s IgA1–3. Although the majority of IgA-secreting cells educated within a mucosal site home back to the same anatomic region, some cells are also found in distant mucosal tissues2–6. These observations underlie the notion of a common mucosal immune system, which holds that anatomically unrelated mucosal sites are functionally connected by a shared immune system2,3. However, the ontological basis of this separation between site of immune education and functionality has remained elusive. Here we show that mice lacking Peyer’s patches (PPs)—small-intestinal lymphoid tissue covered by antigen-sampling M cells—have no immunologic defect in the small-intestinal lamina propria. Surprisingly, the primary immunological abnormality in PP-deficient mice was a reduction in colonic B cells, including plasmablasts but not plasma cells. Adoptive transfer experiments conclusively demonstrated that PP-derived cells preferentially give rise to colonic—but not small-intestinal—B cells and plasmablasts. Finally, these PP-derived colonic B cells were critical for restraining colonic inflammation. Thus, PPs bridge the small-intestinal and colonic immune systems and provide a clear example of immune education being required in an anatomic compartment distinct from the effector site. Our findings, which highlight that the majority of fecal IgA is produced by colonic plasmablasts that originate from PPs, will help inform design of mucosal vaccines.
Lymphoid follicle formation and human vaccination responses recapitulated in an organ-on-a-chip
Authors: Goyal G. , Prabhala P. , Mahajan G. , Bausk B. , Gilboa T. , Xie L. , Zhai Y. , Lazarovits R. , Mansour A. , Kim Min Sun , Curran D. , Long J. M. , Sharma S. , Cohen L. , Levy O. , Prantil-Baun R. , Walt D.R. , Ingber D.E. 
Published: October 2019

ABSTRACTLymphoid follicles (LFs) are responsible for generation of adaptive immune responses in secondary lymphoid organs and form ectopically during chronic inflammation. A human model of LF formation would provide a tool to understand LF development and an alternative to non-human primate models for preclinical evaluation of vaccines. Here, we show that primary human blood B- and T-lymphocytes autonomously assemble into ectopic LFs when cultured in a three-dimensional (3D) extracellular matrix gel within an organ-on-a-chip microfluidic device. Dynamic fluid flow is required for LF formation and prevention of lymphocyte autoactivation. These germinal center-like LFs contain B cells expressing Activation-Induced Cytidine Deaminase and exhibit plasma cell (PC) differentiation upon activation. To explore their utility for vaccine testing, autologous monocyte-derived dendritic cells were integrated into LF Chips. The human LF chips demonstrated improved antibody responses to split virion influenza vaccination compared to 2D cultures, which were enhanced by addition of a squalene-in-water emulsion adjuvant, and this was accompanied by increases in LF size and number. When inoculated with commercial influenza vaccine, PC formation and production of anti-hemagglutinin IgG were observed, as well as secretion of cytokines similar to those observed in vaccinated humans over clinically relevant timescales.
Assessing exposure effects on gene expression
Authors: Reifeis Sarah A. , Hudgens Michael G. , Civelek Mete , Mohlke Karen L. , Love Michael I. 
Published: October 2019

AbstractIn observational genomics datasets, there is often confounding of the effect of an exposure on gene expression. To adjust for confounding when estimating the exposure effect, a common approach involves including potential confounders as covariates with the exposure in a regression model of gene expression. However, when the exposure and confounders interact to influence gene expression, the fitted regression model does not necessarily estimate the overall effect of the exposure. Using inverse probability weighting (IPW) or the parametric g-formula in these instances is straightforward to apply and yields consistent effect estimates. IPW can readily be integrated into a genomics data analysis pipeline with upstream data processing and normalization, while the g-formula can be implemented by making simple alterations to the regression model. The regression, IPW, and g-formula approaches to exposure effect estimation are compared herein using simulations; advantages and disadvantages of each approach are explored. The methods are applied to a case study estimating the effect of current smoking on gene expression in adipose tissue.
A Computational Model of Thalamic Tonic-burst Motor Projection Neurons and Their Regulation by Pallidal GABAergic Neurons
Authors: Azam Md Ali , Kumbhare Deepak , Hadimani Ravi , Toms Jamie , Baron Mark S. , Atulasimha Jayasimha 
Published: October 2019

AbstractA modified computational model of pallidal receiving ventral oral posterior (Vop) thalamocortical motor relay neurons was adapted based on in vivo observations in our rodent model. The model accounts for different input neuronal firing patterns in the primary motor output nucleus of basal ganglia, the globus pallidus interna (GPi) and subsequently generate Vop outputs as observed in vivo under different conditions. Hyperpolarizing input de-inactivates its T-type calcium channel and sets the thalamic neurons in the preferable burst firing mode over a tonic mode and induces low threshold spikes (LTS). In the hyperpolarized state, both spontaneously and in response to excitatory (e.g. corticothalamic) inputs, burst spiking occurs on the crest of the LTS. By selecting and determining the timing and extent of opening of thalamic T-type calcium channels via GABAergic hyperpolarizing input, the GPi precisely regulates Vop-cortical burst motor signaling. Different combinations of tonic, burst, irregular tonic and irregular burst inputs from GPi were used to verify our model. In vivo data obtained from recordings in the entopedunucular nucleus (EP; rodent equivalent of GPi) from resting head restrained healthy and dystonic rats were used to simulate the influences of different inputs from GPi. In all cases, GPi neuronal firing patterns are demonstrated to act as a firing mode selector for thalamic Vop neurons.
Dynamic Transcriptome, Accessible Genome and PGR Cistrome Profiles in the Human Myometrium
Authors: Wu San-Pin , Anderson Matthew L. , Wang Tianyuan , Zhou Lecong , Emery Olivia M. , Li Xilong , DeMayo Francesco J. 
Published: October 2019

AbstractThe myometrium undergoes structural and functional remodeling during pregnancy. We hypothesize that myometrial genomic elements alter correspondingly in preparation for parturition. Human myometrial tissues from nonpregnant (NP) and term pregnant (TP) human subjects were examined by RNAseq, ATACseq and PGR ChIPseq assays to profile transcriptome, assessible genome and PGR occupancy. NP and TP specimens exhibit 2890 differentially expressed genes, reflecting an increase of metabolic, inflammatory and PDGF signaling, among others, in adaptation to pregnancy. At the epigenome level, patterns of accessible genome change between NP and TP myometrium, leading to altered enrichment of binding motifs for hormone and muscle regulators such as the progesterone receptor (PGR), Krüppel-like factors and MEF2A transcription factors. PGR genome occupancy exhibits a significant difference between the two stages of the myometrium, concomitant with distinct transcriptomic profiles including genes such as ENO1, LHDA, and PLCL1 in the glycolytic and calcium signaling pathways. Over-representation of SRF, MYOD and STAT binding motifs in PGR occupying sites further suggests interactions between PGR and major muscle regulators for myometrial gene expression. In conclusion, changes in accessible genome and PGR occupancy are part of the myometrial remodeling process and may serve as mechanisms to formulate the state-specific transcriptome profiles.
CXCL4 links inflammation and fibrosis through transcriptional and epigenetic reprogramming of monocyte-derived cells
Authors: Silva-Cardoso Sandra C , Tao Weiyang , Angiolilli Chiara , Lopes Ana P. , Bekker Cornelis P.J. , Devaprasad Abhinandan , Giovannone Barbara , van Laar Jaap , Cossu Marta , Marut Wioleta , Hack Erik , de Boer Rob J , Boes Marianne , Radstake Timothy R.D.J. , Pandit Aridaman 
Published: October 2019

AbstractFibrosis is a condition shared by numerous inflammatory diseases. Our incomplete understanding of the molecular mechanisms underlying fibrosis has severely hampered effective drug development. CXCL4 is associated with the onset and extent of fibrosis development in systemic sclerosis, a prototypic inflammatory and fibrotic disease. Here, we integrated 65 paired longitudinal transcriptional and methylation profiles from monocyte-derived cells with/without CXCL4 exposure. Using data-driven gene regulatory network analyses, we demonstrate that CXCL4 dramatically alters the trajectory of monocyte differentiation, inducing a novel pro-inflammatory and pro-fibrotic phenotype mediated via key transcriptional regulators including CIITA. CXCL4 exposed monocyte-derived cells directly trigger a fibrotic cascade by producing ECM molecules and inducing myofibroblast differentiation. Inhibition of CIITA mimicked CXCL4 in inducing a pro-inflammatory and pro-fibrotic phenotype, validating the relevance of the gene regulatory network. Our study unveils CXCL4 as a key secreted factor driving innate immune training and forming the long-sought link between inflammation and fibrosis.
Opioids depress breathing through two small brainstem sites
Authors: Bachmutsky Iris , Wei Xin Paul , Kish Eszter , Yackle Kevin 
Published: October 2019

AbstractThe rates of opioid overdose in the United States quadrupled between 1999 and 2017, reaching a staggering 130 deaths per day. This health epidemic demands innovative solutions that require uncovering the key brain areas and cell types mediating the cause of overdose—opioid respiratory depression. Here, we identify two primary changes to breathing after administering opioids. These changes implicate the brainstem’s breathing circuitry which we confirm by locally eliminating the μ-Opiate receptor. We find the critical brain site is the origin of the breathing rhythm, the preBötzinger Complex, and use genetic tools to reveal that just 70-140 neurons in this region are responsible for its sensitivity to opioids. Future characterization of these neurons may lead to novel therapies that prevent respiratory depression while sparing analgesia.
Top-down feature-based cueing modulates conflict-specific ERP components in a Stroop-like task with equiprobable conditions
Authors: Galashan Daniela , Siemann Julia , Herrmann Manfred 
Published: October 2019

AbstractBoth attention and interference processing involve the selection of relevant information from incoming signals. Studies already show that interference decreases when the target location is precued correctly using spatial cueing. Complementary, we examine the effect of feature-based attentional cueing on interference processing. We used a design with equal stimulus probabilities where no response preparation was possible in the valid condition due to a response mapping alternation from trial to trial. The color of the Stroop stimuli was precued either validly or invalidly. Electrophysiological data (EEG) from 20 human participants are reported. We expected reduced interference effects with valid cueing for behavioral data and for both Stroop-associated event-related potential (ERP) components (N450 and sustained positive potential; SP). The N450 showed a significant effect for valid trials but no effect in the invalid condition. In contrast, the SP was absent with valid cueing and present with invalid cues. These findings suggest that focused feature-based attention leads to a more effective attentional selectivity. Furthermore, the top-down influence of feature-based attention differentially affects the N450 and SP components.
The RNA Atlas, a single nucleotide resolution map of the human transcriptome
Authors: Lorenzi Lucia , Chiu Hua-Sheng , Cobos Francisco Avila , Gross Stephen , Volders Pieter-Jan , Cannoodt Robrecht , Nuytens Justine , Vanderheyden Katrien , Anckaert Jasper , Lefever Steve , Goovaerts Tine , Hansen Thomas Birkballe , Kuersten Scott , Nijs Nele , Taghon Tom , Vermaelen Karim , Bracke Ken R. , Saeys Yvan , De Meyer Tim , Deshpande Nandan , Anande Govardhan , Chen Ting-Wen , Wilkins Marc R. , Unnikrishnan Ashwin , De Preter Katleen , Kjems Jørgen , Koster Jan , Schroth Gary P. , Vandesompele Jo , Sumazin Pavel , Mestdagh Pieter 
Published: October 2019

AbstractThe human transcriptome consists of various RNA biotypes including multiple types of non-coding RNAs (ncRNAs). Current ncRNA compendia remain incomplete partially because they are almost exclusively derived from the interrogation of small- and polyadenylated RNAs. Here, we present a more comprehensive atlas of the human transcriptome that is derived from matching polyA-, total-, and small-RNA profiles of a heterogeneous collection of nearly 300 human tissues and cell lines. We report on thousands of novel RNA species across all major RNA biotypes, including a hitherto poorly-cataloged class of non-polyadenylated single-exon long non-coding RNAs. In addition, we exploit intron abundance estimates from total RNA-sequencing to test and verify functional regulation by novel non-coding RNAs. Our study represents a substantial expansion of the current catalogue of human ncRNAs and their regulatory interactions. All data, analyses, and results are available in the R2 web portal and serve as a basis to further explore RNA biology and function.
(p)ppGpp directly regulates translation initiation during entry into quiescence
Authors: Diez Simon , Ryu Jaewook , Caban Kelvin , Gonzalez Ruben L. , Dworkin Jonathan 
Published: October 2019

SummaryMany bacteria exist in a state of metabolic quiescence where they must minimize energy consumption so as to maximize available resources over a potentially extended period of time. As protein synthesis is the most energy intensive metabolic process in a bacterial cell, it would be an appropriate target for downregulation during the transition from growth to quiescence. We find that whenBacillus subtilisexits growth, a subpopulation of cells emerges with very low levels of protein synthesis dependent on synthesis of the nucleotides (p)ppGpp. We show that (p)ppGpp inhibits protein synthesisin vivoandin vitroby preventing the allosteric activation of the essential GTPase Initiation Factor 2 (IF2) during translation initiation. Finally, we demonstrate that IF2 is an authenticin vivotarget of (p)ppGpp during the entry into quiescence, thus providing a mechanistic basis for the observed attenuation of protein synthesis.