bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nutrient acquisition, rather than stress response over diel cycles, drives microbial transcription in a dessicated Namib Desert soil
Authors: León-Sobrino Carlos , Ramond Jean-Baptiste , Maggs-Kölling Gillian , Cowan Don A 
Published: October 2018

AbstractHot desert surface soils are characterised by extremely low water activities for large parts of any annual cycle. It is widely assumed that microbial processes in such soils are very limited. Here we present the first metatranscriptomic survey of microbial community function in a low water activity hyperarid desert soil. Sequencing of total mRNA revealed a diverse and active community, dominated byActinobacteria. Metatranscriptomic analysis of samples taken at different times over three days indicated that most functions did not fluctuate on a diel basis, except for a eukaryotic subpopulation which was induced during the cooler night hours. High levels of transcription of chemoautotrophic carbon fixation genes contrasted with limited expression of photosynthetic genes, indicating that chemoautotrophy is an important alternative to photosynthesis for carbon cycling in desiccated desert soils. Analysis of the transcriptional levels of key N-cycling genes provided strong evidence that soil nitrate was the dominant nitrogen input source. Transcriptional network analyses and taxon-resolved functional profiling suggested that nutrient acquisition processes, and not diurnal environmental variation, were the main drivers of community activity in hyperarid Namib Desert soil. While we also observed significant levels of expression of common stress response genes, these genes were not dominant hubs in the co-occurrence network.
Kinetic Model of Translational Autoregulation
Authors: Tyng Vivian , Kellman Michael E. 
Published: October 2018

AbstractWe investigate dynamics of a kinetic model of inhibitory autoregulation as exemplified when a protein inhibits its own production by interfering with its messenger RNA, known in molecular biology as translational autoregulation. We first show how linear models without feedback set the stage with a nonequilibrium steady state that constitutes the target of the regulation. However, regulation in the simple linear model is far from optimal. The negative feedback mechanism whereby the protein “jams” the mRNA greatly enhances the effectiveness of the control, with response to perturbation that is targeted, rapid, and metabolically efficient. Understanding the full dynamics of the system phase space is essential to understanding the autoregulation process.
The time course of different surround suppression mechanisms
Authors: Schallmo Michael-Paul , Kale Alex M. , Murray Scott O. 
Published: October 2018

AbstractWhat we see depends on the spatial context in which it appears. Previous work has linked the reduction of perceived stimulus contrast in the presence of surrounding stimuli to the suppression of neural responses in early visual cortex. It has also been suggested that this surround suppression depends on at least two separable neural mechanisms, one ‘low-level’ and one ‘higher-level,’ which can be differentiated by their response characteristics. In a recent study, we found evidence consistent with these two suppression mechanisms using psychophysical measurements of perceived contrast. Here, we used EEG to demonstrate for the first time that neural responses in the human occipital lobe also show evidence of two separable suppression mechanisms. Eighteen adults (10 female and 8 male) each participated in a total of 3 experimental sessions, in which they viewed visual stimuli through a mirror stereoscope. The first session was used to definitively identify the C1 component, while the second and third comprised the main experiment. ERPs were measured in response to center gratings either with no surround, or with surrounding gratings oriented parallel or orthogonal, and presented either in the same eye (monoptic) or opposite eye (dichoptic). We found that the earliest ERP component (C1; ∼60 ms) was suppressed in the presence of surrounding stimuli, but that this suppression did not depend on surround configuration, suggesting a low-level suppression mechanism which is not tuned for relative orientation. A later response component (N1; ∼160 ms) showed stronger surround suppression for parallel and monoptic stimulus configurations, consistent with our earlier psychophysical results and a higher-level, binocular, orientation-tuned suppression mechanism. We conclude that these two surround suppression mechanisms have distinct response time courses in the human visual system, which can be differentiated using electrophysiology.
View-channel-depth light-field microscopy: real-time volumetric reconstruction of biological dynamics by deep learning
Authors: Wang Zhaoqiang , Zhu Lanxin , Zhang Hao , Li Guo , Yi Chengqiang , Li Yi , Yang Yicong , Ding Yichen , Zhen Mei , Gao Shangbang , Hsiai Tzung K. , Fei Peng 
Published: October 2018

AbstractLight-field microscopy has emerged as a technique of choice for high-speed volumetric imaging of fast biological processes. However, artefacts, non-uniform resolution, and a slow reconstruction speed have limited its full capabilities for in toto extraction of the dynamic spatiotemporal patterns in samples. Here, we combined a view-channel-depth (VCD) neural network with light-field microscopy to mitigate these limitations, yielding artefact-free three-dimensional image sequences with uniform spatial resolution and three-order-higher video-rate reconstruction throughput. We imaged neuronal activities across moving C. elegans and blood flow in a beating zebrafish heart at single-cell resolution with volume rates up to 200 Hz.
A novel localization based biosensor, SEDAR, visualizes spatio-temporal dynamics of activated Ras in endogenousDrosophilatissues
Authors: Changede Rishita 
Published: October 2018

AbstractChemokine signaling via growth factor receptor tyrosine kinases (RTKs) regulates development, differentiation, growth and disease implying that it is involved in a myriad of cellular processes. A single RTK, for example the Epidermal Growth Factor Receptor (EGFR), is used repeatedly for a multitude of developmental programs. Quantitative differences in magnitude and duration of RTK signaling can bring about different signaling outcomes. Understanding this complex RTK signals requires real time visualization of the signal. To visualize spatio-temporal signaling dynamics, a biosensor calledSEnsitiveDetection ofActivatedRas (SEDAR) was developed. It is a localization-based sensor that binds to activated Ras directly downstream of the endogenous activated RTKs. This binding was reversible and SEDAR expression did not cause any detectable perturbation of the endogenous signal. Using SEDAR, endogenous guidance signaling was visualized during RTK mediated chemotaxis of border cells inDrosophilaovary. SEDAR localized to both the leading and rear end of the cluster but polarized at the leading edge of the cluster. Perturbation of RTKs that led to delays in forward migration of the cluster correlated with loss of SEDAR polarization in the cluster. Gliding or tumbling behavior of border cells was a directly related to the high or low magnitude of SEDAR polarization respectively, in the leading cell showing that signal polarization at the plasma membrane provided information for the migratory behavior. Further, SEDAR localization to the plasma membrane detected EGFR mediated signaling in five distinct developmental contexts. Hence SEDAR, a novel biosensor could be used as a valuable tool to study the dynamics of endogenous Ras activation in real time downstream of RTKs, in three-dimensional tissues, at an unprecedented spatial and temporal resolution.
Impact of temperature and photoperiod on survival and biomarkers of senescence in common woodlouse
Authors: Depeux Charlotte , Samba-Louaka Ascel , Braquart-Varnier Christine , Moreau Jérôme , Lemaître Jean-François , Laverre Tiffany , Pauhlac Hélène , Dechaume-Moncharmont François-Xavier , Gaillard Jean-Michel , Beltran-Bech Sophie 
Published: October 2018

AbstractMost living organisms display a decline in physiological performances when ageing, a process called senescence that is most often associated with increased mortality risk. Previous researches have shown that both the timing and the intensity of senescence vary a lot within and among species, but the role of environmental factors in this variation is still poorly understood. To fill this knowledge gap, we investigated the impact of environmental conditions on the strength of senescence using an experimental design applied to a population of common woodlouseArmadillidium vulgareintensively monitored in the lab. Cellular senescence biomarkers are available in woodlouse and are age-related. These biomarkers provide relevant biomarkers to test the impact of environmental conditions, through changes in temperature and photoperiod, on individuals of the same age maintained in different environmental conditions. We found different effects of the environmental changing: the increasing of day light modification leaded the same effect as age on our senescence biomarkers while temperature modifications leaded the opposite effect as age on the β-galactosidase activity and cell size. We also demonstrated the existence of sex-specific responses to changes in environmental conditions. By using an experimental approach and biomarkers of senescence in woodlouse, we show that environmental conditions and sex both shape the diversity observed in senescence patterns of woodlouse and underline the importance of identifying senescence biomarkers to understand how environmental conditions influence the evolution of senescence.
Behavioural and neural signatures of perceptual evidence accumulation are modulated by pupil-linked arousal
Authors: van Kempen Jochem , Loughnane Gerard M. , Newman Daniel P. , Kelly Simon P. , Thiele Alexander , O’Connell Redmond G , Bellgrove Mark A. 
Published: October 2018

AbstractThe timing and accuracy of perceptual decision making is exquisitely sensitive to fluctuations in arousal. Although extensive research has highlighted the role of neural evidence accumulation in forming decisions, our understanding of how arousal impacts these processes remains limited. Here we isolated electrophysiological signatures of evidence accumulation alongside signals reflecting target selection, attentional engagement and motor output and examined their modulation as a function of both tonic and phasic arousal, indexed by baseline and task-evoked pupil diameter, respectively. For both pupillometric measures, the relationship with reaction time was best described by a second-order, U-shaped, polynomial. Additionally, the two pupil measures were predictive of a unique set of EEG signatures that together represent multiple information processing steps of perceptual decision-making, including evidence accumulation. Finally, we found that behavioural variability associated with fluctuations in both tonic and phasic arousal was largely mediated by variability in evidence accumulation.
Response outcomes gate the impact of expectations on perceptual decisions
Authors: Hermoso-Mendizabal Ainhoa , Hyafil Alexandre , Rueda-Orozco Pavel E. , Jaramillo Santiago , Robbe David , de la Rocha Jaime 
Published: October 2018

ABSTRACTPerceptual decisions are not only determined by current sensory information but are also influenced by expectations based on recent experiences. Can the impact of these expectations be flexibly modulated based on the outcome of previous decisions? We trained rats in several two-alternative forced choice auditory tasks, where the probability to repeat the previous stimulus category was varied in blocks of trials. All rats capitalized on the serial correlations of the stimulus sequence by consistently exploiting atransition bias:a tendency to repeat or alternate their previous response using an internal trial-by-trial estimate of the sequence repeating probability. Surprisingly, this bias was null in trials immediately following an error. The internal estimate however was not reset and it became effective again causing a bias after the next correct response. This ability to rapidly activate and inactivate the bias was captured by a non-linear generative model of rat behavior, whereby a reward-driven modulatory signal gated the use of the latent estimate of the environment statistics on the current decision. These results demonstrate that, based on the outcome of previous choices, rats flexibly modulate how expectations influence their current decisions.
Membrane-cytoskeleton mechanical feedback mediated by myosin-I controls phagocytic efficiency
Authors: Barger Sarah R. , Reilly Nicholas S. , Shutova Maria S. , Li Qingsen , Maiuri Paolo , Mooseker Mark S. , Flavell Richard A. , Svitkina Tatyana , Oakes Patrick W. , Krendel Mira , Gauthier Nils 
Published: October 2018

AbstractPhagocytosis of invading pathogens or cellular debris requires a dramatic change in cell shape driven by actin polymerization. For antibody-covered targets, phagocytosis is thought to proceed through the sequential engagement of Fc-receptors on the phagocyte with antibodies on the target surface, leading to the extension and closure of the phagocytic cup around the target. We have found that two actin-dependent molecular motors, class 1 myosins myosin 1e and myosin 1f, are specifically localized to Fc-receptor adhesions and required for efficient phagocytosis of antibody-opsonized targets. Using primary macrophages lacking both myosin 1e and myosin 1f, we found that without the actin-membrane linkage mediated by these myosins, the organization of individual adhesions is compromised, leading to excessive actin polymerization, slower adhesion turnover, and deficient phagocytic internalization. This work identifies a novel role for class 1 myosins in coordinated adhesion turnover during phagocytosis and supports a model for a membrane-tension based feedback mechanism for phagocytic cup closure.
RNA polymerases display collaborative and antagonistic group behaviors over long distances through DNA supercoiling
Authors: Kim Sangjin , Beltran Bruno , Irnov Irnov , Jacobs-Wagner Christine 
Published: October 2018

SUMMARYTranscription by RNA polymerases (RNAPs) is essential for cellular life. Genes are often transcribed by multiple RNAPs. While the properties of individual RNAPs are well appreciated, it remains less explored whether group behaviors can emerge from co-transcribing RNAPs under most physiological levels of gene expression. Here, we provide evidence inEscherichia colithat well-separated RNAPs can exhibit collaborative and antagonistic group dynamics. Co-transcribing RNAPs translocate faster than a single RNAP, but the density of RNAPs has no significant effect on their average speed. When a promoter is inactivated, RNAPs that are far downstream from the promoter slow down and experience premature dissociation, but only in the presence of other co-transcribing RNAPs. These group behaviors depend on transcription-induced DNA supercoiling, which can also mediate inhibitory dynamics between RNAPs from neighboring divergent genes. Our findings suggest that transcription on topologically-constrained DNA, a norm across organisms, can provide an intrinsic mechanism for modulating the speed and processivity of RNAPs over long distances according to the promoter’s on/off state.
Unsupervised deep learning with variational autoencoders applied to breast tumor genome-wide DNA methylation data with biologic feature extraction
Authors: Titus Alexander J. , Wilkins Owen M. , Bobak Carly A. , Christensen Brock C. 
Published: October 2018

AbstractRecent advances in deep learning, particularly unsupervised approaches, have shown promise for furthering our biological knowledge through their application to gene expression datasets, though applications to epigenomic data are lacking. Here, we employ an unsupervised deep learning framework with variational autoencoders (VAEs) to learn latent representations of the DNA methylation landscape from three independent breast tumor datasets. Through interrogation of methylation-based learned latent dimension activation values, we demonstrate the feasibility of VAEs to track representative differential methylation patterns among clinical subtypes of tumors. CpGs whose methylation was most correlated VAE latent dimension activation values were significantly enriched for CpG sparse regulatory regions of the genome including enhancer regions. In addition, through comparison with LASSO, we show the utility of the VAE approach for revealing novel information about CpG DNA methylation patterns in breast cancer.
Erythrocyte indices, anaemia levels and types in Kenyan injection and non-injection substance users
Authors: Mulaya Khazalwa Emmanuel , Were Tom , Hughes Mulama David , Budambula Valentine 
Published: October 2018

AbstractThe impact of injection and non-injection substance use in HIV infections is an area of great public importance especially with respect to hematologic and immune profiles. Evaluations of hematologic and immune status are critical for better disease classification and clinical management especially of HIV positive substance users. However, not much information is known about the hematologic and immune derangements in HIV infected injection and non-injection substance users. This study, therefore, aimed at determining the laboratory markers of hematologic and immune derangements in HIV infected substance users. Hematologic and immune profiles were evaluated on venous blood specimens obtained from injection substance users, ISU (HIV-infected, n=62 and -uninfected, n=213) and non-injection substance users (HIV-infected, n=33 and -uninfected, n=186); and non-substance using controls (n=56) from Mombasa, coastal town of Kenya. The prevalence of anemia was higher in HIV infected ISU (48.4%) and non-ISU (63.6%) (p<0.0001); and HIV uninfected ISUs (56.3%) compared to HIV-uninfected non-ISUs (39.2%) and non-substance using controls (28.6%; p=0.0028). Hypochromic anaemia was more prevalent in the HIV-infected ISU (50.0%) and non-ISU (61.9%), and HIV-negative ISU (63.3%) relative to the HIV-negative non-ISU (39.7%) and non-substance using controls (56.3%; p=0.0007). Mild immunodeficiency dominated in the HIV infected individuals (HIV-infected ISU, 32.3% and non-ISU, 21.2%) versus HIV-uninfected ISU (16.9%); non-ISU (12.9%); and non-substance users (14.3%) while severe immunosuppression prevailed in HIV infected substance users (ISU, 14.5% and non-ISU, 15.2%) against HIV uninfected substance users (ISU, 5.2% and non-ISU, 3.8%); thus immunosuppression in substance users is aggravated with HIV infection. Moreover, drug-induced immunosuppression is associated with a higher likelihood of anaemia in HIV-uninfected substance users; ISU (OR=3.95, CI=1.934-8.077, p<0.0001) and non-ISU (OR=3.63, CI=1.571-8.39, p=0.003). Altogether, hypochromic anaemia, normochromic anaemia and CD4+ T-helper cytopenia are the most prevalent hemocytopenias in HIV infected and uninfected injection and non-injection substance users.
Within-subject Consistency of Paired Associative Stimulation as Assessed by Linear Mixed Models
Authors: Ottenhoff Myrthe Julia , Fani Lana , Erler Nicole Stephanie , Castricum Jesminne , Obdam Imara Fedora , der Vaart Thijs van , Kushner Steven Aaron , de Wit Marie-Claire Yvette , Elgersma Ype , Tulen Joke H.M. 
Published: October 2018

AbstractPaired associative stimulation (PAS) is a frequently used TMS paradigm that induces long-term potentiation in the human cortex. However, little is known about the within-subject consistency of PAS-induced effects. We determined PAS-induced effects and their consistency in healthy volunteers between two PAS sessions. Additionally, we assessed the benefit of applying linear mixed models (LMMs) to PAS data. Thirty-eight healthy volunteers underwent two identical PAS sessions with a >1 week interval. During each session, motor evoked potentials (MEPs) were assessed once before PAS induction and 3 times after at 30 min intervals. We did not detect any significant potentiation of MEP size after PAS induction. However, MEP size during PAS induction showed significant potentiation over time in both sessions (LR(1)=13.36, p<0.001). Nevertheless, there was poor within-subject consistency of PAS-induced effects both during (ICC=0.15) and after induction (ICC=0.04-0.09). Additionally, statistical model selection procedures demonstrate that a LMM with an unstructured covariance matrix better estimated PAS-induced effects than one with a conventional compound symmetry matrix (LR(34)=214.73, p<0.001). While our results are supportive of a high intra-individual variability of PAS-induced effects, the generalizability of our results is unclear, as we were only partially successful in replicating results from previous PAS studies typically showing potentiation of MEPs during and after PAS induction. We do, however, demonstrate that linear mixed models can improve the reliability of PAS-induced effects estimation.
Arrhythmia Mechanisms and Spontaneous Calcium Release: II - From Calcium Spark to Re-entry and Back
Authors: Colman Michael A. 
Published: October 2018

AbstractMotivationThe role of sub-cellular spontaneous calcium release events (SCRE) in the development of arrhythmia associated with atrial and ventricular tachycardia and fibrillation has yet to be investigated in detail. SCRE may underlie the emergence of spontaneous excitation in single cells, resulting in arrhythmic triggers in tissue. Furthermore, they can promote the substrate for conduction abnormalities. However, the potential interactions with re-entrant excitation have yet to be explored. The primary aim of this study was therefore to apply a novel computational approach to understand the multi-scale coupling between re-entrant excitation and SCRE.MethodsA general implementation of Spontaneous Release Functions - which reproduce the calcium dependent SCRE dynamics of detailed cell models at a significantly reduced computational cost - was used to reproduce SCRE in tissue models. Arrhythmic dynamics, such as rapid pacing and re-entry, were induced in the tissue models and the resulting interactions with SCRE were analysed.ResultsIn homogeneous tissue, the emergence of a spontaneous beat from a single source was observed and the positive role of coupling was demonstrated. Conduction block could be promoted by SCRE by both inactivation of the fast sodium channel as well as focal pacing heterogeneity interactions. Sustained re-entrant excitation promoted calcium overload, and led to the emergence of focal excitations both after termination of re-entry and also during re-entrant excitation. These results demonstrated a purely functional mechanism of re-entry and focal activity localisation, related to the unexcited spiral wave core.ConclusionsSCRE may interact with tissue excitation to promote and perpetuate arrhythmia through multiple mechanisms, including functional localisation and mechanism switching. These insights may be particularly relevant for successful pharmacological management of arrhythmia.