bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing mechanism of sexually dimorphic nervous system differentiation
Authors: Pereira Laura , Aeschimann Florian , Wang Chen , Lawson Hannah , Serrano-Saiz Esther , Portman Douglas S. , Großhans Helge , Hobert Oliver 
Published: September 2018

ABSTRACTIn all animals, sexual differentiation of somatic tissue is precisely timed, yet the molecular mechanisms that control the timing of sexual differentiation, particularly in the brain, are poorly understood. We have used sexually dimorphic molecular, anatomical and behavioral features of theC. elegansnervous system to decipher a regulatory pathway that controls the precise timing of sexual differentiation. We find that the sexually dimorphic differentiation of postmitotic neurons in the male nervous system is abrogated in animals that carry a mutation in the miRNAlet-7and prematurely executed in animals either lacking thelet-7inhibitorlin-28, or the directlet-7targetlin-41, an RNA-binding, posttranscriptional regulator. We show that an isoform of a phylogenetically conserved transcription factor,lin-29a, is a critical target of LIN-41 in controlling sexual maturation of sex-shared neurons.lin-29ais expressed in a male-specific manner in a subset of sex-shared neurons at the onset of sexual maturation.lin-29aacts cell-autonomously in these neurons to control the expression of sexually dimorphic neurotransmitter switches, sensory receptor expression, neurite anatomy and connectivity, and locomotor behavior.lin-29ais not only required but also sufficient to impose male-specific features at earlier stages of development and in the opposite sex. The temporal, sexual and spatial specificity oflin-29aexpression is controlled intersectionally through thelin-28/let-7/lin-41heterochronic pathway, sex chromosome configuration and neuron type-specific terminal selector transcription factors. Two Doublesex-like transcription factors represent additional neuron-type specific targets of LIN-41 and are regulated in a similar intersectional manner, indicating the existence of modular outputs downstream of the heterochronic pathway. In conclusion, we have provided insights into the molecular logic of the timing of sexual differentiation in theC. elegansnervous system. Remarkably, thelin28/let7axis also controls the timing of sexual differentiation in mice and humans thereby hinting toward a striking universality of the control mechanisms of sexual differentiation.
High throughput gene expression profiling of yeast colonies with microgel-culture Drop-seq
Authors: Liu Leqian , Dalal Chiraj , Heineike Ben , Abate Adam 
Published: September 2018

AbstractYeasts can be engineered into “living foundries” for non-natural chemical production by reprogramming their genome using a synthetic biology “design-build-test” cycle. While methods for “design” and “build” are scalable and efficient, “test” remains a labor-intensive bottleneck, limiting the effectiveness of the genetic reprogramming results. Here we describe Isogenic Colony Sequencing (ICO-seq), a massively-parallel strategy to assess the gene expression, and thus engineered pathway efficacy, of large numbers of genetically distinct yeast colonies. We use the approach to characterize opaque-white switching in 658 C. albicans colonies. By profiling transcriptomes of 1642 engineered S. cerevisiae strains, we use it to assess gene expression heterogeneity in a protein mutagenesis library. Our approach will accelerate synthetic biology by allowing facile and cost-effective transcriptional profiling of large numbers of genetically distinct yeast strains.
Gut Microbiota in male patients with chronic traumatic complete spinal cord injury
Authors: Zhang Chao , Zhang Wenhao , Zhang Jie , Jing Yingli , Yang Mingliang , Du Liangjie , Gao Feng , Gong Huiming , Chen Liang , Li Jun , Liu Hongwei , Qin Chuan , Jia Yanmei , Qiao Jiali , Wei Bo , Yu Yan , Zhou Hongjun , Liu Zhizhong , Yang Degang , Li Jianjun 
Published: September 2018

AbstractThis study examined the diversity and structure of gut microbiota in healthy adults and chronic traumatic complete spinal cord injury (SCI) patients, documented neurogenic bowel management of SCI patients. The V3-V4 region of 16S rRNA gene from DNA of 91 fecal samples of 48 healthy and 43 diseased subjects was amplified and sequenced. There was difference in gut microbiota between healthy adult males and females. Neurogenic bowel dysfunction (NBD) was common in patients with chronic traumatic complete SCI, patients with quadriplegia have longer time to defecate than paraplegic patients, with higher NBD scores and heavier neurogenic bowel symptoms. Gut microbiota dysbiosis existed in SCI patients. The abundance of Veillonellaceae and Prevotellaceae increased while Bacteroidaceae and Bacteroides decreased in SCI group. The abundance of Bacteroidaceae, Bacteroides in quadriplegia group and Acidaminococcaceae, Blautia in paraplegia group were significant high than the health male group. Serum biomarkers GLU, HDL, CR and NBD symptoms defecation time, COURSE had significant correlation with microbial community structure. This study presents a comprehensive landscape of gut microbiota in adult male patients with chronic traumatic complete SCI and documents their neurogenic bowel management. The gut microbiota dysbiosis of SCI patients was correlation with serum biomarkers and NBD symptoms.IMPORTANCENeurogenic bowel dysfunction is a major physical and psychological problem in patients with spinal cord injury, which can seriously affect the quality life of them. Gut dysbiosis are highly likely to occur in spinal cord injury patients There are few studies on intestinal microecology after spinal cord injury, and the clinical studies are fewer. It is importance to document their neurogenic bowel management and present a landscape of gut microbiota in them. We found the gut microbiota dysbiosis of spinal cord injury patients was correlation with serum biomarkers and neurogenic bowel dysfunction symptoms. These results may have implications in the next study about metagenomics and precision treatment of neurogenic bowel dysfunction in spinal cord injury patients.
Synthetic Metabolic Pathway for the Production of 1-Alkenes from Lignin-derived Molecules
Authors: Luo Jin , Lehtinen Tapio , Efimova Elena , Santala Ville , Santala Suvi 
Published: September 2018

AbstractIntegration of synthetic metabolic pathways to catabolically diverse chassis provides new opportunities for sustainable production. One attractive scenario is the use of abundant waste material to produce readily collectable product, minimizing production costs. Towards that end, we established the production of semivolatile medium-chain α-olefins from lignin-derived monomers: we constructed 1-undecene synthesis pathway inAcinetobacter baylyiADP1 using ferulate as the sole carbon source. In order to overcome the toxicity of ferulate, we first applied adaptive laboratory evolution, resulting in a highly ferulate-tolerant strain. Next, we demonstrated the 1-undecene production from glucose by heterologously expressing a fatty acid decarboxylase UndA and a thioesterase ‘TesA in the wild type strain. Finally, we constructed the alkene synthesis pathway in the ferulate-tolerant strain. We were able to produce 1-undecene from ferulate and collect the product from the culture headspace without downstream processing. This study demonstrates the potential of bacterial lignin upgradation into value-added products.
Modeling the Electro-chemical Properties of Microbial Opsin ChrimsonR for Application to Optogenetics-based Vision Restoration
Authors: Sabatier Quentin , Joffrois Corentin , Gauvain Grégory , Chavas Joël , Pruneau Didier , Picaud Serge , Benosman Ryad 
Published: September 2018

AbstractOptogenetic activation of neurons [1] have greatly contributed to our understanding of how neural circuits operate, and holds huge promise in the field of neural prosthetics, particularly in sensory restoration. The discovery of new channelrhodopsins, Chrimson — which is 45 nm more red-shifted than any previously discovered or engineered channelrhodopsin — and its mutant ChrimsonR with faster kinetics [2] made this technology available for medical applications. However, a detailed model that would be able to accurately reproduce the membrane potential dynamics in cells transfected with ChrimsonR under light stimulation is missing. We address this issue by developing the first model for the electrochemical behavior of ChrimsonR that predicts its conductance in response to arbitrary light stimulation. Our model captures ON and OFF dynamics of the protein for stimuli with frequencies up to 100 Hz and their relationship with the brightness, as well as its activation curve, the steady-state amplitude of the response as a function of light intensity. Additionally, we capture a slow adaptation mechanism at a timescale at the order of minutes. Our model holds for light intensities covering the whole dynamic range of the channel (from response onset to saturation) and for timescales in the order of up to several minutes. This model is a new step towards modeling the spiking activity of ChrimsonR-expressing neurons, required for the precise control of information transmission in optogenetics-based Brain-Computer Interfaces, and will inform future applications of ChrimsonR based optogenetics.
Multi-laminate Annulus Fibrosus Repair Scaffold with an Interlamellar Matrix Enhances Impact Resistance, Prevents Herniation and Assists in Restoring Spinal Kinematics
Authors: Borem Ryan , Madeline Allison , Vela Ricardo , Gill Sanjitpal , Mercuri Jeremy 
Published: September 2018

AbstractFocal defects in the annulus fibrosus (AF) of the intervertebral disc (IVD) from herniation or surgical injury have detrimental impacts on IVD mechanical function. Thus, biomaterial-based repair strategies, which can restore the mechanical integrity of the AF and support long-term tissue regeneration are needed. Accordingly, a collagen-based multi-laminate scaffold with an underlying “angle-ply” architecture has been previously reported demonstrating similar mechanical properties to native AF tissue. The objectives of this work were to: 1) enhance the biomaterials impact strength, 2) define its contribution to spinal kinematics, and 3) assess its ability to prevent IVD herniation. First, AFRP’s were enriched with a glycosaminoglycan-based (GAG) interlamellar matrix (ILM), and then tested for its radially-directed impact resistance under physiological stresses. Subsequent kinematic testing was conducted using a characterized GAG-enriched AFRP as an AF focal defect closure device. In summary, AFRPs demonstrated 1) incorporation of a GAG-based ILM significantly increased radial impact strength, 2) restoration of axial FSU kinematics and 3) ability to prevent herniation of native IVD tissues. Together, these results suggest that the AFRP demonstrates the mechanical robustness and material properties to restore an IVD’s physiological mechanical function through the adequate closure of an AF focal defect.
Intrahost speciations and host switches shaped the evolution of herpesviruses
Authors: Brito Anderson F. , Pinney John W. 
Published: September 2018

ABSTRACTCospeciation has been suggested to be the main force driving the evolution of herpesviruses, with viral species co-diverging with their hosts along more than 400 million years of evolutionary history. Recent studies, however, have been challenging this assumption, showing that other co-phylogenetic events, such as intrahost speciations and host switches play a central role on their evolution. Most of these studies, however, were performed with undated phylogenies, which may underestimate or overestimate the frequency of certain events. In this study we performed co-phylogenetic analyses using time-calibrated trees of herpesviruses and their hosts. This approach allowed us to (i) infer co-phylogenetic events over time, and (ii) integrate crucial information about continental drift and host biogeography to better understand virus-host evolution. We observed that cospeciations were in fact relatively rare events, taking place mostly after the Late Cretaceous (~100 Millions of years ago). Host switches were particularly common among alphaherpesviruses, where at least 10 transfers were detected. Among beta- and gammaherpesviruses, transfers were less frequent, with intrahost speciations followed by losses playing more prominent roles, especially from the Early Jurassic to the Early Cretaceous, when those viral lineages underwent several intrahost speciations. Our study reinforces the understanding that cospeciations are uncommon events in herpesvirus evolution. More than topological incongruences, mismatches in divergence times were the main disagreements between host and viral phylogenies. In most cases, host switches could not explain such disparities, highlighting the important role of losses and intrahost speciations in the evolution of herpesviruses.
A multi-scale model reveals cellular and physiological mechanisms underlying hyperpolarisation-gated synaptic plasticity
Authors: Xie Yubin , Kazmierczyk Marcel , Graham Bruce P. , Dutia Mayank B. , Stefan Melanie I. , Dutia Mayank B. 
Published: September 2018

AbstractNeurons in the medial vestibular nucleus (MVN) display hyperpolarisation-gated synaptic plasticity, where inhibition believed to come from cerebellar cortical Purkinje cells can induce long-term potentiation (LTP) or long-term depression (LTD) of vestibular nerve afferent synapses. This phenomenon is thought to underlie the plasticity of the vestibulo-ocular reflex (VOR). The molecular and cellular mechanisms involved are largely unknown. Here we present a novel multi-scale computational model, which captures both electrophysiological and biochemical signalling at vestibular nerve synapses on proximal dendrites of the MVN neuron. We show that AMPA receptor phosphorylation at the vestibular synapse depends in complex ways on dendritic calcium influx, which is in turn shaped by patterns of post-synaptic hyperpolarisation and vestibular nerve stimulation. Hyperpolarisation-gated synaptic plasticity critically depends on the activation of LVA calcium channels and on the interplay between CaMKII and PP2B in dendrites of the post-synaptic MVN cell. The extent and direction of synaptic plasticity depend on the strength and duration of hyperpolarisation, and on the relative timing of hyperpolarisation and vestibular nerve stimulation. The multi-scale model thus enables us to explore in detail the interactions between electrophysiological activation and post-synaptic biochemical reaction systems. More generally, this model has the potential to address a wide range of questions about neural signal integration, post-synaptic biochemical reaction systems and plasticity.
Alcohol consumption and mate choice in UK Biobank: comparing observational and Mendelian randomization estimates
Authors: Howe Laurence J , Lawson Daniel J , Davies Neil M , Pourcain Beate St. , Lewis Sarah J , Smith George Davey , Hemani Gibran 
Published: September 2018

AbstractAlcohol use is correlated within spouse-pairs, but it is difficult to disentangle the effects of alcohol consumption on mate-selection from social factors or cohabitation leading to spouses becoming more similar over time. We hypothesised that genetic variants related to alcohol consumption may, via their effect on alcohol behaviour, influence mate selection.Therefore, in a sample of over 47,000 spouse-pairs in the UK Biobank we utilised a well-characterised alcohol related variant, rs1229984 in ADH1B, as a genetic proxy for alcohol use. We compared the phenotypic concordance between spouses for self-reported alcohol use with the association between an individual’s self-reported alcohol use and their partner’s rs1229984 genotype using Mendelian randomization. This was followed up by an exploration of the spousal genotypic concordance for the variant and an analysis determining if relationship length may be related to spousal alcohol behaviour similarities.We found strong evidence that both an individual’s self-reported alcohol consumption and rs1229984 genotype are associated with their partner’s self-reported alcohol use. The Mendelian randomization analysis found that each unit increase in an individual’s weekly alcohol consumption increased their partner’s alcohol consumption by 0.26 units (95% C.I. 0.15, 0.38; P=1.10×10-5). Furthermore, the rs1229984 genotype was concordant within spouse-pairs, suggesting that some spousal concordance for alcohol consumption existed prior to cohabitation. Although the SNP is strongly associated with ancestry, our results suggest that this concordance is unlikely to be explained by population stratification. Overall, our findings suggest that alcohol behaviour directly influences mate selection.
Active Transport of Membrane Components by Self-Organization of the Min Proteins
Authors: Shih YL , Huang LT , Tu YM , Lee BF , Bau YC , Hong CY , Lee HL , Shih YP , Hsu MF , Chen JS , Lu ZX , Chao L 
Published: September 2018

ABSTRACTHeterogeneous distribution of components in the biological membrane is critical in the process of cell polarization. However, little is known about the mechanisms that can generate and maintain the heterogeneous distribution of the membrane components. Here we report that the propagating wave patterns of the bacterial Min proteins can impose corresponding steric pressure on the membrane to establish a directional accumulation of the membrane components, resulting in segregation of the components in the membrane. The diffusivity, influenced by the membrane anchor of the component, and the repulsed ability, influenced by the steric property of the soluble region of the component and molecular crowding, determine the differential spatial distribution of the component in the membrane. Thus, transportation of the membrane components by the Min proteins follows a simple physical principle, which resembles a linear peristaltic pumping process, to selectively segregate and maintain heterogeneous distribution of materials in the membrane.
SLiM 3: Forward genetic simulations beyond the Wright–Fisher model
Authors: Haller Benjamin C. , Messer Philipp W. 
Published: September 2018

AbstractWith the desire to model population genetic processes under increasingly realistic scenarios, forward genetic simulations have become a critical part of the toolbox of modern evolutionary biology. The SLiM forward genetic simulation framework is one of the most powerful and widely used tools in this area. However, its foundation in the Wright–Fisher model has been found to pose an obstacle to implementing many types of models; it is difficult to adapt the Wright–Fisher model, with its many assumptions, to modeling ecologically realistic scenarios such as explicit space, overlapping generations, individual variation in reproduction, density-dependent population regulation, individual variation in dispersal or migration, local extinction and recolonization, mating between subpopulations, age structure, fitness-based survival and hard selection, emergent sex ratios, and so forth. In response to this need, we here introduce SLiM 3, which contains two key advancements aimed at abolishing these limitations. First, the new non-Wright–Fisher or “nonWF” model type provides a much more flexible foundation that allows the easy implementation of all of the above scenarios and many more. Second, SLiM 3 adds support for continuous space, including spatial interactions and spatial maps of environmental variables. We provide a conceptual overview of these new features, and present several example models to illustrate their use. These two key features allow SLiM 3 models to go beyond the Wright–Fisher model, opening up new horizons for forward genetic modeling.
Automated in situ profiling of chromatin modifications resolves cell types and gene regulatory programs
Authors: Janssens Derek H. , Wu Steven J. , Sarthy Jay F. , Meers Michael P. , Myers Carrie H. , Olson James M. , Ahmad Kami , Henikoff Steven 
Published: September 2018

AbstractOur understanding of eukaryotic gene regulation is limited by the complexity of protein-DNA interactions that comprise the chromatin landscape and by inefficient methods for characterizing these interactions. We recently introduced CUT&RUN, an antibody-targeted nuclease-cleavage method that profiles DNA-binding proteins, histones and chromatin modifying proteins in situ with exceptional sensitivity and resolution. Here we describe an automated CUT&RUN platform and apply it to characterize the chromatin landscapes of human cell lines. We find that CUT&RUN profiles of histone modifications crisply demarcate active and repressed chromatin regions, and we develop a continuous metric to identify cell-type specific promoter and enhancer activities. We test the ability of automated CUT&RUN to profile frozen tumor samples, and find that our method readily distinguishes two diffuse midline gliomas by their subtype-specific gene expression programs. The easy, cost-effective workflow makes automated CUT&RUN an attractive tool for high-throughput characterization of cell types and patient samples.
Exploring the Binding Mechanism between Human Profilin (PFN1) and Polyproline-10 through Binding Mode Screening
Authors: Zhang Leili , Bell David R. , Luan Binquan , Zhou Ruhong 
Published: September 2018

AbstractThe large magnitude of protein-protein interaction (PPI) pairs within the human interactome necessitates the development of predictive models and screening tools to better understand this fundamental molecular communication. However, despite enormous efforts from various groups to develop predictive techniques in the last decade, PPI complex structures are in general still very challenging to predict due to the large number of degrees of freedom. In this study, we use the binding complex of human profilin (PFN1) and polyproline-10 (P10) as a model system to examine various approaches, with the aim of going beyond normal protein docking for PPI prediction and evaluation. The potential of mean force (PMF) was first obtained from the timeconsuming umbrella sampling, which confirmed that the most stable binding structure identified by the maximal PMF difference is indeed the crystallographic binding structure. Moreover, crucial residues previously identified in experimental studies, W3, H133 and S137 of PFN1, were found to form favorable hydrogen bonds with P10, suggesting a zipping process during the binding between PFN1 and P10. We then explored both regular molecular dynamics (MD) and steered molecular dynamics (SMD) simulations, seeking for better criteria of ranking the PPI prediction. Despite valuable information obtained from conventional MD simulations, neither the commonly used interaction energy between the two binding parties nor the long-term root mean square displacement (RMSD) correlates well with the PMF results. On the other hand, with a sizable collection of trajectories, we demonstrated that the average rupture work calculated from SMD simulations correlates fairly well with the PMFs (R2= 0.67), making it a promising PPI screening method.