bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell transcriptional dynamics and origins of neuronal diversity in the developing mouse neocortex
Authors: Telley L. , Agirman G. , Prados J. , Fièvre S. , Oberst P. , Vitali I. , Nguyen L. , Dayer A. , Jabaudon D. 
Published: September 2018

During cortical development, distinct subtypes of glutamatergic neurons are sequentially born and differentiate from dynamic populations of progenitors. The neurogenic competence of these progenitors progresses as corticogenesis proceeds; likewise, newborn neurons transit through sequential states as they differentiate. Here, we trace the developmental transcriptional trajectories of successive generations of apical progenitors (APs) and isochronic cohorts of their daughter neurons using parallel single-cell RNA sequencing between embryonic day (E) 12 and E15 in the mouse cerebral cortex. Our results identify the birthdate- and differentiation stage-related transcriptional dynamics at play during corticogenesis. As corticogenesis proceeds, APs transit through embryonic age-dependent molecular states, which are transmitted to their progeny to generate successive initial daughter cell identities. In neurons, essentially conserved post-mitotic differentiation programs are applied onto these distinct AP-derived ground states, allowing temporally-regulated sequential emergence of specialized neuronal cell types. Molecular temporal patterning of sequentially-born daughter neurons by their respective mother cell thus underlies emergence of neuronal diversity in the neocortex.One Sentence SummaryDuring corticogenesis, temporally dynamic molecular birthmarks are transmitted from progenitors to their post-mitotic progeny to generate neuronal diversity.
The neural basis of hand choice: An fMRI investigation of the Posterior Parietal Interhemispheric Competition model
Authors: Fitzpatrick Aoife M. , Dundon Neil M. , Valyear Kenneth F. 
Published: September 2018

AbstractThe current study investigates a new neurobiological model of human hand choice: The Posterior Parietal Interhemispheric Competition (PPIC) model. The model specifies that neural populations in bilateral posterior intraparietal and superior parietal cortex (pIP-SPC) encode actions in hand-specific terms, and compete for selection across and within hemispheres. Actions with both hands are encoded bilaterally, but the contralateral hand is overrepresented. We use a novel fMRI paradigm to test the PPIC model. Participants reach to visible targets while in the scanner, and conditions involving free choice of which hand to use (Choice) are compared with when hand-use is instructed. Consistent with the PPIC model, bilateral pIP-SPC is preferentially responsive for the Choice condition, and for actions made with the contralateral hand. In the right pIP-SPC, these effects include anterior intraparietal and superior parieto-occipital cortex. Left dorsal premotor cortex, and an area in the right lateral occipitotemporal cortex show the same response pattern, while the left inferior parietal lobule is preferentially responsive for the Choice condition and when using the ipsilateral hand. Behaviourally, hand choice is biased by target location – for targets near the left/right edges of the display, the hand in ipsilateral hemispace is favoured. Moreover, consistent with a competitive process, response times are prolonged for choices to more ambiguous targets, where hand choice is relatively unbiased, and fMRI responses in bilateral pIP-SPC parallel this pattern. Our data provide support for the PPIC model, and reveal a selective network of brain areas involved in free hand choice, including bilateral posterior parietal cortex, left-lateralized inferior parietal and dorsal premotor cortices, and the right lateral occipitotemporal cortex.
Landscape of stimulation-responsive chromatin across diverse human immune cells
Authors: Calderon Diego , Nguyen Michelle L. T. , Mezger Anja , Kathiria Arwa , Nguyen Vinh , Lescano Ninnia , Wu Beijing , Trombetta John , Ribado Jessica V. , Knowles David A. , Gao Ziyue , Parent Audrey V. , Burt Trevor D. , Anderson Mark S. , Criswell Lindsey A. , Greenleaf William J. , Marson Alexander , Pritchard Jonathan K. 
Published: September 2018

AbstractThe immune system is controlled by a balanced interplay among specialized cell types transitioning between resting and stimulated states. Despite its importance, the regulatory landscape of this system has not yet been fully characterized. To address this gap, we collected ATAC-seq and RNA-seq data under resting and stimulated conditions for 25 immune cell types from peripheral blood of four healthy individuals, and seven cell types from three fetal thymus samples. We found that stimulation caused widespread chromatin remodeling, including a large class of response elements shared between stimulated B and T cells. Furthermore, several autoimmune traits showed significant heritability in stimulation-responsive elements from distinct cell types, highlighting the critical importance of these cell states in autoimmunity. Use of allele-specific read-mapping identified thousands of variants that alter chromatin accessibility in particular conditions. Notably, variants associated with changes in stimulation-specific chromatin accessibility were not enriched for associations with gene expression regulation in whole blood – a tissue commonly used in eQTL studies. Thus, large-scale maps of variants associated with gene regulation lack a condition important for understanding autoimmunity. As a proof-of-principle we identified variant rs6927172, which links stimulated T cell-specific chromatin dysregulation in theTNFAIP3locus to ulcerative colitis and rheumatoid arthritis. Overall, our results provide a broad resource of chromatin landscape dynamics and highlight the need for large-scale characterization of effects of genetic variation in stimulated cells.
Rapidly Assessing the Quality of Targeted Proteomics Experiments Through Monitoring Stable-isotope Labeled Standards
Authors: Gibbons Bryson C. , Fillmore Thomas L. , Gao Yuqian , Moore Ronald J. , Liu Tao , Nakayasu Ernesto S. , Metz Thomas O. , Payne Samuel H. 
Published: September 2018

AbstractTargeted proteomics experiments based on selected reaction monitoring (SRM) have gained wide adoption in clinical biomarker, cellular modeling and numerous other biological experiments due to their highly accurate and reproducible quantification. The quantitative accuracy in targeted proteomics experiments is reliant on the stable-isotope, heavy-labeled peptide standards which are spiked into a sample and used as a reference when calculating the abundance of endogenous peptides. Therefore, the quality of measurement for these standards is a critical factor in determining whether data acquisition was successful. With improved MS instrumentation that enables the monitoring of hundreds of peptides in hundreds to thousands of samples, quality assessment is increasingly important and cannot be performed manually. We present Q4SRM, a software tool that rapidly checks the signal from all heavy labeled peptides and flags those that fail quality control metrics. Using four metrics, the tool detects problems both with individual SRM transitions and the collective group of transitions that monitor a single peptide. The program’s speed enables its use at the point of data acquisition and can be ideally run immediately upon the completion of an LC-SRM-MS analysis.
Morphological profile determines the frequency of spontaneous calcium events in astrocytic processes
Authors: Wu Yu-Wei , Gordleeva Susan , Tang Xiaofang , Shih Pei-Yu , Dembitskaya Yulia , Semyanov Alexey 
Published: September 2018

AbstractAstrocytes express a complex repertoire of intracellular Ca2+ transients (events) that represent a major form of signaling within individual cells and in the astrocytic syncytium. These events have different spatiotemporal profiles, which are modulated by neuronal activity. Spontaneous Ca2+ events appear more frequently in distal astrocytic processes and independently from each other. However, little is known about the mechanisms underlying such subcellular distribution of the Ca2+ events. Here we identify the initiation points of the Ca2+ events within the territory of single astrocytes expressing genetically encoded Ca2+ indicator GCaMP2 in culture or in hippocampal slices. We found that most of the Ca2+ events start in thin distal processes. Our mathematical model demonstrated that a high surface-to-volume (SVR) of the thin processes leads to increased amplitude of baseline Ca2+ fluctuations caused by a stochastic opening of Ca2+ channels in the plasma membrane. Suprathreshold fluctuations trigger Ca2+-induced Ca2+ release (CICR) from the Ca2+ stores by activating inositol 1,4,5-trisphosphate (IP3) receptors. In agreement with the model prediction, the spontaneous Ca2+ events frequency depended on the extracellular Ca2+ concentration. Astrocytic depolarization by high extracellular K+ increased the frequency of the Ca2+ events through activation of voltage-gated Ca2+ channels (VGCC) in cultured astrocytes. Our results suggest that the morphological profile of the astrocytic processes is responsible for tuning of the Ca2+ event frequency. Therefore, the structural plasticity of astrocytic processes can be directly translated into changes in astrocytic Ca2+ signaling. This may be important for both physiological and pathological astrocyte remodeling.Main pointsMajority of spontaneous Ca2+ events start in thin astrocytic processesHigher surface-to-volume ratio of the process is responsible for larger intracellular Ca2+ fluctuationsLarger intracellular Ca2+ fluctuations trigger Ca2+-dependent Ca2+ release
Long-term phenotypic effects following vitrified-thawed embryo transfer in a rabbit model
Authors: Garcia-Dominguez Ximo , Peñaranda David. S. , Estruch Guillem , Blanca José , García-Carpintero Victor , Cañizares Joaquín , Marco-Jiménez Francisco , Vicente José Salvador 
Published: September 2018

AbstractSince the first human was conceived through in vitro fertilisation in 1978, over 6.5 million babies have been born by assisted reproductive technologies (ARTs). Although most ART babies and children seem healthy, in recent years several studies have evidenced a potential impact of ARTs on long-term development and health. Herein, we have developed an animal model to determine whether vitrified embryo transfer procedure induces phenotypic changes over the growth performance and in the complementary transcriptomic and proteomic analyses at hepatic level. To this end, 2 populations were developed; vitrified embryos transferred to the surrogate mothers (VT) and naturally conceived animals (NC). After delivery, animals were weighed weekly from 1 to 20 weeks of age. In adulthood, animals were euthanized and organs were harvested and weighed. After that, liver tissue was used to identify changes in the transcriptomic and proteomic profile. At adulthood, VT group showed significant lower body, liver and heart weight. After functional analysis of RNA-Seq data, a subset of 96 differentially expressed transcripts in VT animal were related to alteration in zinc homeostasis, lipid metabolism, and hepatic immune pathways. After proteomic analysis, a subset of 76 differentially expressed proteins also revealed some disturbed metabolic pathways related with the lipid and glycan metabolism, and an impaired oxidative metabolism related to ATP synthesis in the mitochondria. Current findings suggest that progeny derived after transfer of vitrified embryos have long-term consequences on growth rate and vital organs weights in adulthood, correlated with molecular signatures at transcriptomic and proteomic level of hepatic tissue.
Regenerative capacity in the lamprey spinal cord is not altered after a repeated transection
Authors: Hanslik Kendra L. , Allen Scott R. , Harkenrider Tessa L. , Fogerson Stephanie M. , Guadarrama Eduardo , Morgan Jennifer R. 
Published: September 2018

AbstractThe resilience of regeneration in vertebrate tissues is not well understood. Yet understanding how well tissues can regenerate after repeated insults, and identifying any limitations, is an important step towards elucidating the underlying mechanisms of tissue plasticity. This is particularly challenging in tissues such as the nervous system, which contain a large number of terminally differentiated cells (i.e. neurons) and that often exhibits limited regenerative potential in the first place. However, unlike mammals that exhibit very little spinal cord regeneration, many non-mammalian vertebrate species, including lampreys, fishes, amphibians and reptiles, regenerate their spinal cords and functionally recover even after a complete spinal cord transection. It is well established that lampreys undergo full functional recovery of swimming behaviors after a single spinal cord transection, which is accompanied by tissue repair at the lesion as well as axon and synapse regeneration. Here, using the lamprey model, we begin to explore resilience of spinal cord regeneration after a second spinal re-transection. We report that by all functional and anatomical measures tested, the lampreys regenerated after spinal re-transection just as robustly as after single transections. Recovery of swimming behaviors, axon regeneration, synapse and cytoskeletal distributions, and neuronal survival were nearly identical after a single spinal transection or a repeated transection. Thus, regenerative potential in the lamprey spinal cord is largely unaffected by spinal re-transection, indicating a greater persistent regenerative potential than exists in some other highly-regenerative models. These findings establish a new path for uncovering pro-regenerative targets that could be deployed in non-regenerative conditions.
Temporal dynamics of bacterial and fungal communities during the infection of Brassica rapa roots by the protist Plasmodiophora brassicae: The impact of a pathogen on the plant root and rhizosphere microbiota
Authors: Lebreton Lionel , Guillerm-Erckelboudt Anne-Yvonne , Gazengel Kévin , Linglin Juliette , Ourry Morgane , Glory Pascal , Sarniguet Alain , Daval Stéphanie , Manzanares-Dauleux Maria J. , Mougel Christophe 
Published: September 2018

AbstractThe temporal dynamics of rhizosphere and root microbiota composition was compared between healthy and infected Chinese cabbage plants by the pathogen Plasmodiophora brassicae. When inoculated with P. brassicae, disease was measured at five sampling dates from early root hair infection to late gall development. The first symptoms of clubroot disease appeared 14 days after inoculation (DAI) and increased drastically between 14 and 35 DAI. The structure of microbial communities associated to rhizosphere soil and root from healthy and inoculated plants was characterized through high-throughput DNA sequencing of bacterial (16S) and fungal (18S) molecular markers and compared at each sampling date. In healthy plants, Proteobacteria and Bacteroidetes bacterial phyla dominated the rhizosphere and root microbiota of Chinese cabbage. Rhizosphere bacterial communities contained higher abundances of Actinobacteria and Firmicutes compared to the roots. Moreover, a drastic shift of fungal communities of healthy plants occurred between the two last sampling dates, especially in plant roots, where most of Ascomycota fungi dominated until they were replaced by a fungus assigned to the Chytridiomycota phylum. Parasitic invasion by P. brassicae disrupted the rhizosphere and root-associated community assembly at a late step during the root secondary cortical infection stage of clubroot disease. At this stage, Flavisolibacter and Streptomyces in the rhizosphere, and Bacillus in the roots, were drastically less abundant upon parasite invasion. Rhizosphere of plants colonized by P. brassicae was significantly more invaded by the Chytridiomycota fungus, which could reflect a mutualistic relationship in this compartment between these two microorganisms.
Transcriptomic characterization of signaling pathways associated with osteoblastic differentiation of MC-3T3E1 cells
Authors: Luttrell Louis M. , Dar Moahad S. , Gesty-Palmer Diane , El-Shewy Hesham M. , Robinson Katherine M. , Haycraft Courtney J. , Barth Jeremy L. 
Published: September 2018

AbstractBone remodeling involves the coordinated actions of osteoclasts, which resorb the calcified bony matrix, and osteoblasts, which refill erosion pits created by osteoclasts to restore skeletal integrity and adapt to changes in mechanical load. Osteoblasts are derived from pluripotent mesenchymal stem cell precursors, which undergo differentiation under the influence of a host of local and environmental cues. To characterize the autocrine/paracrine signaling networks associated with osteoblast maturation and function, we performed gene network analysis using complementary “agnostic” DNA microarray and “targeted” NanoString™nCounter datasets derived from murine MC3T3-E1 cells induced to undergo synchronized osteoblastic differentiationin vitro. Pairwise datasets representing changes in gene expression associated with growth arrest (day 2 to 5 in culture), differentiation (day 5 to 10 in culture), and osteoblast maturation (day 10 to 28 in culture) were analyzed using Ingenuity Systems™Pathways Analysis to generate predictions about signaling pathway activity based on the temporal sequence of changes in target gene expression. Our data indicate that some pathways known to be involved in osteoblast differentiation, e.g. Wnt/β-catenin signaling, are most active early in the process, while others, e.g. TGFβ/BMP, cytokine/JAK-STAT and TNFα/RANKL signaling, increase in activity as differentiation progresses. Collectively, these pathways contribute to the sequential expression of genes involved in the synthesis and mineralization of extracellular matrix. These results provide insight into the temporal coordination and complex interplay between signaling networks controlling gene expression during osteoblast differentiation. A more complete understanding of these processes may aid the discovery of novel methods to promote osteoblast development for the trea™ent of conditions characterized by low bone mineral density.
Functional analysis of Scratch2 domains: implications in the evolution of Snail transcriptional repressors
Authors: Nakamura Kanno Tatiane Yumi , Fogo Mariana Soares , Goes Carolina Purcell , Vieceli Felipe M. , Irene Yan Chao Yun 
Published: September 2018

AbstractThe Snail superfamily of transcription factors have a modular organization and their similarities and divergences are the basis for subdividing the superfamily into the Snail1/2 and Scratch families. As it is generally accepted that the Snail and Scratch families originated through gene duplication, understanding the functional contribution of each module could provide us with further insight about the molecular and functional evolution of the Snail superfamily. Thus, in this work, we investigated the function of the SNAG and SCRATCH domains in chicken Scratch2. Through evolutionary comparison analysis we identified a novel HINGE domain that lies between the SNAG and SCRATCH domain. Similar to members of the Snail1/2 families, Scratch2- mediated transcriptional repression requires SNAG and nuclear localization requires the zinc-finger domain. We also identified a novel HINGE domain that lies between the SNAG and SCRATCH domain. HINGE is highly conserved in amniotes. Single mutations of the conserved Tyrosine and Serine residues of HINGE downregulated Scratch2-mediated transcriptional repression. This effect depended on the presence of the SCRATCH domain.
How do firms utilize the deferred patent examination system? Evidence from Korea
Authors: Cao Siwei , Lei Zhen , Oh Junbyoung 
Published: September 2018

Purpose
The purpose of this paper is to investigate firm behaviors on patent examination request under the deferred patent examination system in Korea. The authors examine firm decisions on whether and when to request patent examinations when they face both uncertainty about invention’s value and market competition.

Design/methodology/approach
The authors provide a simple theoretical model and test a couple of hypothesis using Korea patent data. The authors employ KIPO (Korean intellectual patent office) patent applications data during 2006–2009 and incorporate it with firm financial data retrieved from1 Korea investor service-financial analysis system (KIS-FAS) database in Korea. The authors use the variation in the probability of lapsed patent applications filed in the same year and in the same technology field (at the four-digit IPC class level) of a patent application i as a proxy for the value of uncertainty, and further use one minus a firm’s market share (at the three-digit SIC industry level) as an indicator of the market competition faced by the firm/applicant.

Findings
The authors find that the examination requests of firms in Korea have interesting bipolar distribution, and both uncertainty about an invention’s value and market competition have significant impacts on firm’s decision for examination request. Applicants tend to utilize option value of waiting when uncertainty is high, but market competition attenuates the option value: the higher the competition, the less likely applicants are to delay or forego examination.

Originality/value
The authors’ study makes interesting contributions to the literature on the optimal design of the patent system in general and the deferred patent examination request system in particular. By considering the roles of both uncertainty and market competition in firm decisions, it provides a more comprehensive perspective on the deferred patent examination system. The study also provides empirical evidences on the broader research topic regarding firm decision for irreversible investment when faced with both uncertainty and competition, for which a strand of theoretical literature exists but empirical literature is largely limited. This study, which explicitly takes into account uncertainty and market competition, extends this line of empirical literature and fills the gap in the literature.
Employees’ preferences for services and facilities offered in serviced offices
Authors: Appel-Meulenbroek Rianne , van de Kar Mike , van den Berg Pauline , Arentze Theo 
Published: September 2018

PurposeServiced offices are popular, offering many services and facilities to attract tenants. As research showed that most business centres occupy similar buildings, services are important to differentiate. All kinds of people use them (from freelancers to employees of large corporates) and their characteristics are likely to influence how they value different services. This study aims to identify which services/facilities are perceived as most important and whether end-user characteristics explain differences between users regarding these preferences. Serviced office owners and operators can use the insights obtained from this study to differentiate their product offer from competitors and aim for specific tenant market segments.Design/methodology/approachData were collected through a questionnaire among 137 end-users in 13 serviced offices in The Netherlands. With principal component analysis, 31 services and facilities could be reduced to six independent factors and four additional services. Multiple regression analysis was used to determine effects of user characteristics (employee demographics, job characteristics and reasons for using serviced offices) on perceived importance of each service/facility (factor).FindingsResults showed that organisational characteristics had little effect on perceived importance of services and facilities. Especially the time spent at the office and the reasons for using it showed effects on importance of different services and facilities. Amenities like a gym and childcare were not deemed important by most of the respondents.Originality/valueSo far, research on office users focused largely on single-tenant offices and large corporates. Serviced offices have only been studied from the supply side until now.