bluuebunny/crossref_metadata_2025_split huggingface dataset:
The conservation landscape of the human ribosomal RNA gene repeats
Authors: Agrawal Saumya , Ganley Austen R.D. 
Published: April 2018

ABSTRACTRibosomal RNA gene repeats (rDNA) encode ribosomal RNA, a major component of ribosomes. Ribosome biogenesis is central to cellular metabolic regulation, and several diseases are associated with rDNA dysfunction, notably cancer, However, its highly repetitive nature has severely limited characterization of the elements responsible for rDNA function. Here we make use of phylogenetic footprinting to provide a comprehensive list of novel, potentially functional elements in the human rDNA. Complete rDNA sequences for six non-human primate species were constructed usingde novowhole genome assemblies. These new sequences were used to determine the conservation profile of the human rDNA, revealing 49 conserved regions in the rDNA intergenic spacer (IGS). To provide insights into the potential roles of these conserved regions, the conservation profile was integrated with functional genomics datasets. We find two major zones that contain conserved elements characterised by enrichment of transcription-associated chromatin factors, and transcription. Conservation of some IGS transcripts in the apes underpins the potential functional significance of these transcripts and the elements controlling their expression. Our results characterize the conservation landscape of the human IGS, and suggest that noncoding transcription and chromatin elements are conserved and important features of this unique genomic region.
Prenatal alcohol exposure and facial morphology in a UK cohort
Authors: Howe Laurence J , Sharp Gemma C , Hemani Gibran , Zuccolo Luisa , Richmond Stephen , Lewis Sarah J 
Published: April 2018

AbstractHigh levels of prenatal alcohol exposure are known to cause an array of adverse outcomes including foetal alcohol syndrome (FAS); however, the effects of low to moderate exposure are less-well characterised. Previous findings suggest that differences in normal-range facial morphology may be a marker for alcohol exposure and related adverse effects. Therefore, in the Avon Longitudinal Study of Parents and Children, we tested for an association between maternal alcohol consumption and six FAS-related facial phenotypes in their offspring, using both self-report questionnaires and the maternal genotype at rs1229984 inADH1Bas measures of maternal alcohol consumption. In both self-reported alcohol consumption (N=4,233) and rs1229984 genotype (N=3,139) analyses, we found no strong statistical evidence for an association between maternal alcohol consumption and facial phenotypes tested. The directions of effect estimates were compatible with the known effects of heavy alcohol exposure, but confidence intervals were largely centred around zero. We conclude that, in a sample representative of the general population, there is no strong evidence for an effect of prenatal alcohol exposure on normal-range variation in facial morphology.
Mapping molecular datasets back to the brain regions they are extracted from: Remembering the native countries of hypothalamic expatriates and refugees
Authors: Khan Arshad M. , Grant Alice H. , Martinez Anais , Burns Gully A.P.C. , Thatcher Brendan S. , Anekonda Vishwanath T. , Thompson Benjamin W. , Roberts Zachary S. , Moralejo Daniel H. , Blevins James E. 
Published: April 2018

AbstractThis article, which includes novel unpublished data along with commentary and analysis, focuses on approaches to link transcriptomic, proteomic, and peptidomic datasets mined from brain tissue to the original locations within the brain that they are derived from using digital atlas mapping techniques. We use, as an example, the transcriptomic, proteomic and peptidomic analyses conducted in the mammalian hypothalamus. Following a brief historical overview, we highlight studies that have mined biochemical and molecular information from the hypothalamus and then lay out a strategy for how these data can be linked spatially to the mapped locations in a canonical brain atlas where the data come from, thereby allowing researchers to integrate these data with other datasets across multiple scales. A key methodology that enables atlas-based mapping of extracted datasets – laser-capture microdissection – is discussed in detail, with a view of how this technology is a bridge between systems biology and systems neuroscience.
FMRI processing with AFNI: Some comments and corrections on “Exploring the Impact of Analysis Software on Task fMRI Results”
Authors: Taylor Paul A. , Chen Gang , Glen Daniel R. , Rajendra Justin K. , Reynolds Richard C. , Cox Robert W. 
Published: April 2018

ABSTRACTA recent study posted on bioRxiv by Bowring, Maumet and Nichols aimed to compare results of FMRI data that had been processed with three commonly used software packages (AFNI, FSL and SPM). Their stated purpose was to use “default” settings of each software’s pipeline for task-based FMRI, and then to quantify overlaps in final clustering results and to measure similarity/dissimilarity in the final outcomes of packages. While in theory the setup sounds simple (implement each package’s defaults and compare results), practical realities make this difficult. For example, different softwares would recommend different spatial resolutions of the final data, but for the sake of comparisons, the same value must be used across all. Moreover, we would say that AFNI does not have an explicit default pipeline available: a wide diversity of datasets and study designs are acquired across the neuroimaging community, often requiring bespoke tailoring of basic processing rather than a “one-size-fits-all” pipeline. However, we do have strong recommendations for certain steps, and we are also aware that the choice of a given step might place requirements on other processing steps. Given the very clear reporting of the AFNI pipeline used in Bowring et al. paper, we take this opportunity to comment on some of these aspects of processing with AFNI here, clarifying a few mistakes therein and also offering recommendations. We provide point-by-point considerations of using AFNI’s processing pipeline design tool at the individual level, afni_proc.py, along with supplementary programs; while specifically discussed in the context of the present usage, many of these choices may serve as useful starting points for broader processing. It is our intention/hope that the user should examine data quality at every step, and we demonstrate how this is facilitated in AFNI, as well.
Real-time functional connectivity-based neurofeedback of amygdala-frontal pathways reduces anxiety
Authors: Zhao Zhiying , Yao Shuxia , Li Keshuang , Sindermann Cornelia , Zhou Feng , Zhao Weihua , Li Jianfu , Lührs Michael , Goebel Rainer , Kendrick Keith M. , Becker Benjamin 
Published: April 2018

AbstractDeficient emotion regulation and exaggerated anxiety represent a major transdiagnostic psychopathological marker. On the neural level these deficits have been closely linked to impaired, yet treatment-sensitive, prefrontal regulatory control over the amygdala. Gaining direct control over these pathways could therefore provide an innovative and promising strategy to regulate exaggerated anxiety. To this end the current proof-of-concept study evaluated the feasibility, functional relevance and maintenance of a novel connectivity-informed real-time fMRI neurofeedback training. In a randomized within-subject sham-controlled design high anxious subjects (n = 26) underwent real-time fMRI-guided training to enhance connectivity between the ventrolateral prefrontal cortex (vlPFC) and the amygdala (target pathway) during threat exposure. Maintenance of regulatory control was assessed after three days and in the absence of feedback. Training-induced changes in functional connectivity of the target pathway and anxiety ratings served as primary outcomes. Training of the target, yet not the sham-control, pathway significantly increased amygdala-vlPFC connectivity and decreased subjective anxiety levels. On the individual level stronger connectivity increases were significantly associated with anxiety reduction. At follow-up, volitional control over the target pathway and decreased anxiety level were maintained in the absence of feedback. The present results demonstrate for the first time that successful self-regulation of amygdala-prefrontal top-down regulatory circuits may represent a novel strategy to control anxiety. As such, the present findings underscore both the critical contribution of amygdala-prefrontal circuits to emotion regulation and the therapeutic potential of connectivity-informed real-time neurofeedback.
Discovery of a new path for red blood cell generation in the mouse embryo
Authors: Pinheiro Irina , Bölükbaşi Özge Vargel , Ganter Kerstin , Sabou Laura A. , Tew Vick Key , Bolasco Giulia , Shvartsman Maya , Pavlovich Polina V. , Buness Andreas , Nikolakopoulou Christina , Bergiers Isabelle , Kouskoff Valerie , Lacaud Georges , Lancrin Christophe 
Published: April 2018

AbstractErythropoiesis occurs through several waves during embryonic development. Although the source of the primitive wave is well characterized, the origin of erythrocytes later in embryogenesis is less clear due to overlaps between the different erythroid waves. Using the miR144/451-GFP mouse model to track cells expressing the erythroid microRNAs miR144/451, we identified cells co-expressing VE-Cadherin and GFP in the yolk sac between E9.5 and E12. This suggested the existence of hemogenic endothelial cells committed to erythropoiesis (Ery-HEC). We showed that these cells were capable of generating erythrocytesex vivoand we demonstrated that the formation of Ery-HEC was independent of theRunx1gene expression. Using transcriptome analysis, we demonstrated that these cells coexpressed endothelial and erythroid genes such asHbb-bh1andGata1but we were surprised to detect the primitive erythroid genesAqp3andAqp8suggesting the formation of primitive erythrocytes at a much later time point than initially thought. Finally, we showed that enforced expression ofGata1in endothelial cells was enough to initiate the erythroid transcriptional program.
Molecular dynamics suggests antiviral compounds active against Dengue Virus show similar binding patterns to Zika Virus proteins
Authors: de Lima Neto Daniel Ferreira , Soares Anderson Pereira , Pour Shahab Zaki , Baez Ayda Susana Ortiz , de Castro Neuhaus Patrick , de Melo Freire Caio Cesar , Bonafé Carlos Francisco Sampaio 
Published: April 2018

AbstractThe Zika virus (ZIKV) arrival in Brazilian territory brought to light the need for preparedness regarding arboviruses in Brazil. Compound screening is a cumbersome process dependent upon in vitro testing and validation. Recently, virtual screening methods have improved precision and reliability providing a framework for in silico testing of lead compound candidates. Here we have applied these methods on compounds that were previously shown to be active against Dengue virus in vitro, taking the structural information of such compounds and applying docking methods to identify putative binding sites. A molecular dynamics approach was also used to refine the docking results. The computational experiments ran here suggests that compounds such as Epigallocatechin Gallate, Ergotamine and Avermectin-B1a bind to active sites on the viral enzymes NS5 and NS3, as well as on its Envelope protein. Refinement shows that such bindings were not lost during the production run and key regions on both enzymes were structurally displaced on average over the simulation time. Interestingly there is no documented drug interactions among these candidates, raising the possibility of drug combinations during treatments. Moreover, the candidate compounds have been extensively studied, thus providing important information regarding intracellular interactions caused by them, which are also associated with pathways exploited by the virus, suggesting possible side interactions hindering the replication process.
A network of epigenomic and transcriptional cooperation encompassing an epigenomic master regulator in cancer
Authors: Wilson Stephen , Filipp Fabian V. 
Published: April 2018

AbstractCoordinated experiments focused on transcriptional responses and chromatin states are well-equipped to capture different epigenomic and transcriptomic levels governing the circuitry of a regulatory network. We propose a workflow for the genome-wide identification of epigenomic and transcriptional cooperation to elucidate transcriptional networks in cancer. Gene promoter annotation in combination with network analysis and sequence-resolution of enriched transcriptional motifs in epigenomic data reveals transcription factor families that act synergistically with epigenomic master regulators. A close teamwork of the transcriptional and epigenomic machinery was discovered. The network is tightly connected and includes the histone lysine demethylase KDM3A, basic helix-loop-helix factors MYC, HIF1A, and SREBF1, as well as differentiation factors AP1, MYOD1, SP1, MEIS1, ZEB1 and ELK1. In such a cooperation network, one component opens the chromatin, another one recognizes gene-specific DNA motifs, others scaffold between histones, cofactors, and the transcriptional complex. In cancer, due to the ability to team up with transcription factors, epigenetic factors concert mitogenic and metabolic gene networks, claiming the role of a cancer master regulators or epioncogenes.Specific histone modification patterns are commonly associated with open or closed chromatin states, and are linked to distinct biological outcomes by transcriptional activation or repression. Disruption of patterns of histone modifications is associated with loss of proliferative control and cancer. There is tremendous therapeutic potential in understanding and targeting histone modification pathways. Thus, investigating cooperation of chromatin remodelers and the transcriptional machinery is not only important for elucidating fundamental mechanisms of chromatin regulation, but also necessary for the design of targeted therapeutics.
Solving for X: evidence for sex-specific autism biomarkers across multiple transcriptomic studies
Authors: Lee Samuel C. , Quinn Thomas P. , Lai Jerry , Kong Sek Won , Hertz-Picciotto Irva , Glatt Stephen J. , Crowley Tamsyn M. , Venkatesh Svetha , Nguyen Thin 
Published: April 2018

AbstractAutism spectrum disorder (ASD) is a markedly heterogeneous condition with a varied phenotypic presentation. Its high concordance among siblings, as well as its clear association with specific genetic disorders, both point to a strong genetic etiology. However, the molecular basis of ASD is still poorly understood, although recent studies point to the existence of sex-specific ASD pathophysiologies and biomarkers. Despite this, little is known about how exactly sex influences the gene expression signatures of ASD probands. In an effort to identify sex-dependent biomarkers (and characterise their function), we present an analysis of a single paired-end post-mortem brain RNA-Seq data set and a meta-analysis of six blood-based microarray data sets. Here, we identify several genes with sex-dependent dysregulation, and many more with sex-independent dysregulation. Moreover, through pathway analysis, we find that these sex-independent biomarkers have substantially different biological roles than the sex-dependent biomarkers, and that some of these pathways are ubiquitously dysregulated in both post-mortem brain and blood. We conclude by synthesizing the discovered biomarker profiles with the extant literature, by highlighting the advantage of studying sex-specific dysregulation directly, and by making a call for new transcriptomic data that comprise large female cohorts.
Regulation of evidence accumulation by pupil-linked arousal processes
Authors: Keung Waitsang , Hagen Todd A. , Wilson Robert C. 
Published: April 2018

AbstractIntegrating evidence over time is crucial for effective decision making. For simple perceptual decisions, a large body of work suggests that humans and animals are capable of integrating evidence over time fairly well, but that their performance is far from optimal. This suboptimality is thought to arise from a number of different sources including: (1) noise in sensory and motor systems, (2) unequal weighting of evidence over time, (3) order effects from previous trials and (4) irrational side biases for one choice over another. In this work we investigated these di.erent sources of suboptimality and how they are related to pupil dilation, a putative correlate of norepinephrine tone. In particular, we measured pupil response in humans making a series of decisions based on rapidly-presented auditory information in an evidence accumulation task. We found that people exhibited all four types of suboptimality, and that some of these suboptimalities covaried with each other across participants. Pupillometry showed that only noise and the uneven weighting of evidence over time, the ‘integration kernel’, were related to the change in pupil response during the stimulus. Moreover, these two different suboptimalities were related to different aspects of the pupil signal, with the individual differences in pupil response associated with individual differences in integration kernel, while trial-by-trial fluctuations in pupil response were associated with trial-by-trial fluctuations in noise. These results suggest that di.erent sources of suboptimality in human perceptual decision making are related to distinct pupil-linked processes possibly related to tonic and phasic norepinephrine activity.
Lactococcin B is inactivated by intrinsic proteinase PrtP digestion inLactococcus lactissubsp.lactisBGMN1-501
Authors: Vukotic Goran , Polovic Natalija , Mirkovic Nemanja , Jovcic Branko , Stanisavljevic Nemanja , Fira Djordje , Kojic Milan 
Published: April 2018

AbstractIn our previous study, we showed that PrtP is able to impair bacteriocin LcnB activity despite being produced by the same organism, and even if they were encoded by the same plasmid. However, exact cleavage site within LcnB bacteriocin, as well as the activity of the resulting peptides remained unknown. Here we further explored the interplay between these two proteins and defined, using mass spectrometry, that the hydrolysis occurs between the sixth and seventh amino acid on the N terminus of LcnB. Although it was suspected that the cleaved form of LcnB could retain some level of activity, both chemically synthesized and recombinant variant of truncated LcnB exhibited no antimicrobial activity. Wild type form of LcnB was recombinantly overexpressed using the same expression system, its antimicrobial activity was tested before and after the treatment with PrtP proteinase, and the degradation products were analyzed with reverse-phase high-pressure liquid chromatography. The results confirmed the inactivity of the truncated LcnB and additionally corroborated the PrtP cleavage site in LcnB bacteriocin.ImportanceLactococcal enzyme PrtP, considered as a growth promoting factor, is involved in casein breakdown and enabling bacteria efficient growth in amino acids-poor, but protein-rich media. However, its interaction with bacteriocins was not known until recently. Bacteriocin LcnB can also be considered as growth promoting factor, since its known physiological role mirrors in preventing competing bacteria of reaching high growth densities. In this manuscript, we define the exact peptide bond inside the bacteriocin LcnB which is recognized by PrtP. This N-terminal removal of six amino acids completely inactivates the bacteriocin. The biological function of such action remains elusive. It is unexpected that in the same strain one enzyme inactivates a protein important for survival, unless it is some type of regulation.
Tricellular junction proteins promote disentanglement of daughter and neighbour cells during epithelial cytokinesis
Authors: Wang Zhimin , Bosveld Floris , Bellaïche Yohanns 
Published: April 2018

AbstractIn epithelial tissue, new cell-cell junctions are formed upon cytokinesis. To understand junction formation during cytokinesis, we explored in Drosophila epithelium, de novo formation of tricellular septate junctions (TCJs). We found that upon midbody formation, the membranes of the two daughter cells and of the neighbouring cells located below the adherens junction (AJ) remain entangled in a 4-cell structure apposed to the midbody. The septate junction protein Discs-Large and components of the TCJ, Gliotactin and Anakonda accumulate in this 4-cell structure. Subsequently, a basal movement of the midbody parallels the detachment of the neighbouring cell membranes from the midbody, the disengagement of the daughter cells from their neighbours and the reorganisation of TCJs between the two daughter cells and their neighbouring cells. While the movement of midbody is independent of the Alix and Shrub abscission regulators, the loss of Gliotactin or Anakonda function impedes both the resolution of the connection between the daughter-neighbour cells and midbody movement. TCJ proteins therefore control an additional step of cytokinesis necessary for the disentanglement of the daughter cells and their neighbours during cytokinesis.
Anxiety induced by extra-hypothalamic BDNF deficiency instigates resistance to diet-induced obesity
Authors: Xie Xiangyang , Yang Haili , An Juan Ji , Liao Guey-Ying , Xu Zhi-Xiang , Tan Jiwei , Xu Baoji 
Published: April 2018

SUMMARYAnxiety disorders are associated with body weight changes in humans. However, mechanisms underlying anxiety-related weight changes remain poorly understood. Using Emx1Cre/+ mice, we deleted the gene for brain-derived neurotrophic factor (BDNF) in the cortex, hippocampus, and some parts of the amygdala. The resulting mutant mice displayed elevated anxiety levels and were markedly lean when fed either chow diet or high-fat diet (HFD). The mice showed higher levels of sympathetic activity, thermogenesis and lipolysis in both brown and white adipose tissues, and higher oxygen consumption and body temperature, compared with control mice. They were still lean at thermoneurality when fed HFD, indicating elevated basal metabolism in addition to activated thermogenesis. Anxiety induced by site-specific Bdnf deletion similarly increased energy expenditure and minimized HFD-induced weight gain. These results reveal that anxiety can stimulate adaptive thermogenesis and basal metabolism by activating sympathetic nervous system, which enhances lipolysis and limits weight gain.