bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered sleep architecture, rapid eye movement sleep, and neural oscillation in a mouse model of human chromosome 16p11.2 microdeletion
Authors: Lu Hung-Chi , Pollack Harvey , Lefante John J , Mills Alea A , Tian Di 
Published: December 2018

AbstractSleep abnormalities are common among children with neurodevelopmental disorders. The human chr16p11.2 microdeletion is associated with a range of neurological and neurobehavioral abnormalities. Previous studies of a mouse model of human chr16p11.2 microdeletion (chr16p11.2df/+) have demonstrated pathophysiological changes at the synapses in the hippocampus and striatum; however, the impact of this genetic abnormality on system level brain functions, such as sleep and neural oscillation, has not been adequately investigated. Here, we show that chr16p11.2df/+ mice have altered sleep architecture, with increased wake time and reduced time in rapid eye movement (REM) and non-REM (NREM) sleep. Importantly, several measurements of REM sleep are significantly changed in deletion mice. The REM bout number and the bout number ratio of REM to NREM are decreased in mutant mice, suggesting a deficit in REM-NREM transition. The average REM bout duration is shorter in mutant mice, indicating a defect in REM maintenance. In addition, whole-cell patch clamp recording of the ventrolateral periaqueductal gray (vlPAG)-projecting gamma-aminobutyric acid (GABA)ergic neurons in the lateral paragigantocellular nucleus of ventral medulla of mutant mice reveal that these neurons, which are important for NREM–REM transition and REM maintenance, have hyperpolarized resting membrane potential and increased membrane resistance. These changes in intrinsic membrane properties suggest that these projection-specific neurons of mutant mice are less excitable, and thereby may play a role in deficient NREM–REM transition and REM maintenance. Furthermore, mutant mice exhibit changes in neural oscillation involving multiple frequency classes in several vigilance states. The most significant alterations occur in the theta frequency during wake and REM sleep.
Salivary Biomarkers of Parenting Stress in Mothers Under Community Criminal Justice Supervision
Authors: Rieder Jenna K. , Goshin Lorie S. , Sissoko D.R. Gina , Kleshchova Olena , Weierich Mariann R. 
Published: December 2018

BackgroundCommunity criminal justice supervised mothers are an underserved population who experience high rates of psychological distress and unique parenting challenges, but little is known about physiological stress system function in this population.ObjectiveWe tested the salivary biomarkers of the sympathetic nervous system (SNS) and hypothalamic–pituitary–adrenal (HPA) axis function as predictors of subjective maternal stress.MethodWe recruited 23 mothers (age:M= 35.6 years,SD= 9.3 years; 35% Hispanic, 22% Black, 22% White, 22% multiracial) who were court mandated to a residential treatment center. We measured salivary alpha-amylase (AA) and cortisol, which index SNS and HPA activity, respectively, before and after a naturalistic reminder of a stressful parenting experience. We assessed self-reported parenting stress using the Parenting Stress Index–Short Form (PSI-SF) subscales Parental Distress, Parent–Child Dysfunctional Interactions, and Difficult Child. We used regression to test AA and cortisol mean levels and reactivity as predictors of subscale scores.ResultsMean, but not reactive, salivary stress biomarker levels were associated with parenting stress domains. Mean cortisol levels predicted scores on the Parent–Child Dysfunctional Interaction subscale (adj.R2= .48), whereas mean AA predicted Difficult Child subscale scores (adj.R2= .28).DiscussionOur results demonstrate the potential predictive utility of AA and cortisol as salivary biomarkers of maternal stress in community-supervised mothers. Given that maternal stress is associated with criminal recidivism and child behavioral health in this population, these biomarkers could potentially inform interventions to improve dyadic health and social outcomes.
Autologous Fat Injection for the Correction of Facial Depression Resulting From Silent Sinus Syndrome
Authors: Lim Byeong Woo , Jung Joo Hyun , Kim Seon Tae , Kim Dong Hyun , Park Jung Woo , Cha Heung Eog , Kang Il Gyu 
Published: December 2018

Abstract
The case of a 59-year-old woman who underwent endoscopic sinus surgery for right maxillary sinusitis 5 years before visiting our otorhinolaryngologic department complaining of right-sided facial depression was described in this study. Computed tomography (CT) scans revealed right facial depression and retraction of the orbital floor due to a hypoplastic right maxillary sinus. Symptoms and CT findings corresponded with silent sinus syndrome. Facial depression is a rare symptom in silent sinus syndrome and is well corrected by autologous fat transfer.
Human Genes Escaping X-inactivation Revealed by Single Cell Expression Data
Authors: Katsir Kerem Wainer , Linial Michal 
Published: December 2018

AbstractBackgroundIn mammals, sex chromosomes pose an inherent imbalance of gene expression between sexes. In each female somatic cell, random inactivation of one of the X-chromosomes restores this balance. While most genes from the inactivated X-chromosome are silenced, 15-25% are known to escape X-inactivation (termed escapees). The expression levels of these genes are attributed to sex-dependent phenotypic variability.ResultsWe used single-cell RNA-Seq to detect escapees in somatic cells. As only one X-chromosome is inactivated in each cell, the origin of expression from the active or inactive chromosome can be determined from the variation of sequenced RNAs. We analyzed primary, healthy fibroblasts (n=104), and clonal lymphoblasts with sequenced parental genomes (n=25) by measuring the degree of allelic-specific expression (ASE) from heterozygous sites. We identified 24 and 49 candidate escapees, at varying degree of confidence, from the fibroblast and lymphoblast transcriptomes, respectively. We critically test the validity of escapee annotations by comparing our findings with a large collection of independent studies. We find that most genes (66%) from the unified set were previously reported as escapees. Furthermore, out of the overlooked escapees, 11 are long noncoding RNA (lncRNAs).ConclusionsX-chromosome inactivation and escaping from it are robust, permanent phenomena that are best studies at a single-cell resolution. The cumulative information from individual cells increases the potential of identifying escapees. Moreover, despite the use of a limited number of cells, clonal cells (i.e., same X-chromosomes are coordinately inhibited) with genomic phasing are valuable for detecting escapees at high confidence. Generalizing the method to uncharacterized genomic loci resulted in lncRNAs escapees which account for 20% of the listed candidates. By confirming genes as escapees and propose others as candidates from two different cell types, we contribute to the cumulative knowledge and reliability of human escapees.
Spectral memory: Illumination-evoked plasticity
Authors: Adeyefa-Olasupo Ifedayo-Emmanuel 
Published: December 2018

AbstractHere human trichromats were presented with two types of scenes – geometric and real-world scenes –tinted with a shade of colour in order to destabilize the perceived illumination, and chromaticity of the retinal image of each scene. Each trichromat was instructed to adjust the chromaticity of the object embedded within each scene until its surface appeared devoid of any hue in the DKL colour space which spans two chromatic opponent axes – the S–(L+M) and L– M axis – and a luminance axis – the L+M axis. The following observations were made : (i) across scenes, adjustments were dispersed along the S–(L+M) axis, along which daylight is known to vary; (ii) across trichromats, for the geometric scenes, adjustments were biased towards the S pole of the S–(L+M) axis for one group (group 1), and towards the (L+M) pole for the other group (group 2); (iii) for the real-world scenes, adjustments for both groups systematically converged towards the (L+M) pole. These results suggest that when the core set of priors upon which the human visual system typically relies become ill-equipped, the human visual system is able to recruit one of the two illumination priors – PriorS or PriorL+M – in combination with the representation it has formed over time about the spectral composition of the illuminant associated with scenes the trichromatic observer is currently being exposed to within its ecological niche, as it attempts to stabilize the chromaticity of the retinal image of real-world scenes.
Gamblers: an Antibiotic-induced Evolvable Cell Subpopulation Differentiated by Reactive-oxygen-induced General Stress Response
Authors: Pribis John P , García-Villada Libertad , Zhai Yin , Lewin-Epstein Ohad , Wang Anthony , Liu Jingjing , Xia Jun , Mei Qian , Fitzgerald Devon M. , Bos Julia , Austin Robert , Herman Christophe , Bates David , Hadany Lilach , Hastings P.J. , Rosenberg Susan M 
Published: December 2018

SUMMARYAntibiotics can induce mutations that cause antibiotic resistance. Yet, despite their importance, mechanisms of antibiotic-promoted mutagenesis remain elusive. We report that the fluoroquinolone antibiotic ciprofloxacin (cipro) induces mutations that cause drug resistance by triggering differentiation of a mutant-generating cell subpopulation, using reactive oxygen species (ROS) to signal the sigma-S (σS) general-stress response. Cipro-generated DNA breaks activate the SOS DNA-damage response and error-prone DNA polymerases in all cells. However, mutagenesis is restricted to a cell subpopulation in which electron transfer and SOS induce ROS, which activate the σSresponse, allowing mutagenesis during DNA-break repair. When sorted, this small σS-response-“on” subpopulation produces most antibiotic cross-resistant mutants. An FDA-approved drug prevents σSinduction specifically inhibiting antibiotic-promoted mutagenesis. Furthermore, SOS-inhibited cell division, causing multi-chromosome cells, is required for mutagenesis. The data support a model in which within-cell chromosome cooperation together with development of a “gambler” cell subpopulation promote resistance evolution without risking most cells.
Focal adhesion-generated cues in extracellular matrix regulate cell migration by local induction of clathrin-coated plaques
Authors: Bucher Delia , Mukenhirn Markus , Sochacki Kem A. , Saharuka Veronika , Huck Christian , Zambarda Chiara , Taraska Justin W. , Cavalcanti-Adam Elisabetta Ada , Boulant Steeve 
Published: December 2018

AbstractClathrin is a unique scaffold protein, which forms polyhedral lattices with flat and curved morphology. The function of curved clathrin-coated pits in forming endocytic structures is well studied. On the contrary, the role of large flat clathrin arrays, called clathrin-coated plaques, remains ambiguous. Previous studies suggested an involvement of plaques in cell adhesion. However, the molecular origin leading to their formation and their precise functions remain to be determined. Here, we study the origin and function of clathrin-coated plaques during cell migration. We revealed that plaque formation is intimately linked to extracellular matrix (ECM) modification by focal adhesions (FAs). We show that in migrating cells, FAs digest the ECM creating extracellular topographical cues that dictate the future location of clathrin-coated plaques. We identify Eps15 and Eps15R as key regulators for the formation of clathrin-coated plaques at locally remodelled ECM sites. Using a genetic silencing approach to abrogate plaque formation and 3D-micropatterns to spatially control the location of clathrin-coated plaques, we could directly correlate cell migration directionality with the formation of clathrin-coated plaques and their ability to recognize extracellular topographical cues. We here define the molecular mechanism regulating the functional interplay between FAs and plaques and propose that clathrin-coated plaques act as regulators of cell migration promoting contact guidance-mediated collective migration in a cell-to-cell contact independent manner.
The telomeric Cdc13-Stn1-Ten1 complex regulates RNA polymerase II transcription
Authors: Calvo Olga , Grandin Nathalie , Jordán-Pla Antonio , Miñambres Esperanza , González-Polo Noelia , Pérez-Ortín José E. , Charbonneau Michel 
Published: December 2018

SummarySpecialized telomeric proteins have an essential role in maintaining genome stability through chromosome end protection and telomere length regulation. In the yeastSaccharomyces cerevisiae, the evolutionary conserved CST complex, composed of the Cdc13, Stn1 and Ten1 proteins, largely contributes to these functions. Here, we report the existence of genetic interactions betweenTEN1and several genes coding for transcription regulators. Molecular assays confirmed this novel function of Ten1 and further established that it regulates the occupancies of RNA polymerase II and the Spt5 elongation factor within transcribed genes. Since Ten1, but also Cdc13 and Stn1, were found to physically associate with Spt5, we propose that Spt5 represents the target of CST in transcription regulation. Moreover, CST physically associates with Hmo1, previously shown to mediate the architecture of S phase-transcribed genes. The fact that, genome-wide, the promoters of genes down-regulated in theten1-31mutant are prefentially bound by Hmo1, leads us to propose a potential role for CST in synchronizing transcription with replication fork progression following head-on collisions.
Resistance to diet induced obesity in the apolipoprotein E deficient mouse is associated with an attenuated transcriptional response in visceral fat
Authors: Fitzgibbons Timothy P. , Kelly Mark , Kim Jason K. , Czech Michael P. 
Published: December 2018

ABSTRACTThe apolipoprotein E knockout (EKO) mouse is a well-established model of atherosclerosis. Macrophages in the arterial intima of EKO mice serve a protective role, scavenging oxidatively modified LDL in order to protect cells from toxic free cholesterol. Recent studies have highlighted a similar role for macrophage foam cells in restraining the increased rates of lipolysis in adipose tissue of obese and fasting mice. Interestingly, EKO adipocytes have been shown to have increased rates of lipolysisin vitro. Therefore, the aim of this study was to examine how apoE deficiency might alter the transcriptional response of visceral adipose tissue (VAT) to high fat diet (HFD). EKO mice fed HFD for 24 weeks gained less fat mass and were more insulin sensitive than their wild type (WT) littermates. Metabolic cages showed that HFD EKO mice had increased post-prandial oxygen consumption and increased serum β-hydroxybutyrate. DNA microarrays revealed that EKO VAT was comparatively insensitive to HFD in terms of alterations in gene expression, with only 0.1% of probe sets differentially expressed. In contrast, the VAT of WT mice had a 30 fold more extensive alteration in gene expression (3% of probes sets), characterized predominantly by increased expression of immune cell specific genes. In addition, analysis ofa prioridetermined gene sets revealed broad down-regulation of PPARγ target and fatty acid catabolism genes in WT VAT, and increased expression of lipid storage and cholesterol synthesis genes. In comparison, expression of PPARγ target genes was not down-regulated in EKO VAT and expression of fatty acid oxidation genes was increased. In summary, we report three novel findings with regards to metabolism in the EKO mouse: 1) increased post-prandial oxygen consumption, 2) increased serum β hydroxybutyrate concentrations and 3) a dramatically less robust transcriptional response to HFD in EKO VAT. These findings suggest that limiting adipocyte exposure to dietary fatty acids may be an attractive therapy for diet induced obesity, provided that compensatory mechanisms that prevent hyperlipidemia can be activated.
cis-Regulatory Chromatin Contacts in Neural Cells Reveal Contributions of Genetic Variants to Complex Neurological Disorders
Authors: Song Michael , Yang Xiaoyu , Ren Xingjie , Maliskova Lenka , Li Bingkun , Jones Ian , Wang Chao , Jacob Fadi , Wu Kenneth , Traglia Michela , Tam Tsz Wai , Jamieson Kirsty , Lu Si-Yao , Ming Guo-Li , Yao Jun , Weiss Lauren A. , Dixon Jesse , Judge Luke M. , Conklin Bruce R , Song Hongjun , Gan Li , Shen Yin 
Published: December 2018

AbstractMutations in gene regulatory elements have been associated with a wide range of complex neurological disorders. However, due to their inherent cell type-specificity and difficulties in characterizing their regulatory targets, our ability to identify causal genetic variants has remained limited. To address these constraints, we perform integrative analysis of chromatin interactions using promoter capture Hi-C (pcHi-C), open chromatin regions using ATAC-seq, and transcriptomes using RNA-seq in four functionally distinct neural cell types: iPSC-induced excitatory neurons and lower motor neurons, iPSC-derived hippocampal dentate gyrus (DG)-like neurons, and primary astrocytes. We identify hundreds of thousands of long-rangecisinteractions between promoters and distal promoter-interacting regions (PIRs), enabling us to link regulatory elements to their target genes and reveal putative pathways that are dysregulated in disease. We validate several novel PIRs using CRISPR techniques in human excitatory neurons, demonstrating thatCDK5RAP3, STRAP, andDRD2are transcriptionally regulated by physically linked enhancers. Finally, we show that physical chromatin interactions mediate genetic interactions in autism spectrum disorder (ASD). Our study illustrates how characterizing the 3D epigenome elucidates novel regulatory relationships in the central nervous system (CNS), shedding light on previously unknown functions for noncoding variants in complex neurological disorders.
Estrogen promotes pro-resolving microglial behaviour and phagocytic cell clearance through the actions of annexin A1
Authors: Loiola Rodrigo Azevedo , Wickstead Edward S. , Solito Egle , McArthur Simon 
Published: December 2018

AbstractLocal production of estrogen rapidly follows brain tissue injury, but the role this hormone plays in regulating the response to neural damage or in the modulation of mediators regulating inflammation is in many ways unclear. Using the murine BV2 microglia model as well as primary microglia from wild-type and annexin A1 (AnxA1) null mice, we have identified two related mechanisms whereby estradiol can modulate microglial behaviour in a receptor specific fashion. Firstly, estradiol, via estrogen receptor β (ERβ), enhanced the phagocytic clearance of apoptotic cells, acting through increased production and release of the protein AnxA1. Secondly, stimulation of either ERβ or the G protein coupled estrogen receptor GPER promoted the adoption of an anti-inflammatory/proresolving phenotype, an action similarly mediated through AnxA1. Together, these data suggest the hypothesis that locally produced estrogen acts through AnxA1 to exert powerful pro-resolving actions, controlling and limiting brain inflammation and ultimately protecting this highly vulnerable organ. Given the high degree of receptor selectivity in evoking these responses, we suggest that the use of selective estrogen receptor ligands may hold therapeutic promise in the treatment of neuroinflammation, avoiding unwanted generalised effects.
Snf2 controls pulcherriminic acid biosynthesis and connects pigmentation and antifungal activity of the yeastMetschnikowia pulcherrima
Authors: Gore-Lloyd Deborah , Sumann Inés , Brachmann Alexander O. , Schneeberger Kerstin , Ortiz-Merino Raúl A. , Moreno-Beltrán Mauro , Schläfli Michael , Kirner Pascal , Kron Amanda Santos , Wolfe Kenneth H. , Piel Jörn , Ahrens Christian H. , Henk Daniel , Freimoser Florian M. 
Published: December 2018

AbstractMetschnikowia pulcherrimasynthesizes the red pigment pulcherrimin, from cyclodileucine (cyclo(Leu-Leu)) as a precursor, and exhibits strong antifungal activity against notorious plant pathogenic fungi such asBotrytisandGibberella(i.e.,Fusarium). This yeast therefore has great potential for biocontrol applications against fungal diseases; particularly in the phyllosphere where this species is frequently found. To elucidate the molecular basis of the antifungal activity ofM. pulcherrima, we compared a wildtype strain with a spontaneously occurring, pigmentless, weakly antagonistic mutant derivative. Whole genome sequencing of the wildtype and mutant strains identified a point mutation that creates a premature stop codon in the transcriptional regulatorSNF2in the mutant strain. Complementation of thesnf2mutant strain with the wildtypeSNF2gene restored pigmentation and recovered the strong antifungal activity ofM. pulcherrimaagainst plant pathogensin vitroand on cherries. Ultra-performance liquid chromatography-high resolution heated electrospray ionization mass spectrometry (UPLC HR HESI-MS) proved the presence and structure of the pulcherrimin precursors cyclo(Leu-Leu) and pulcherriminic acid and also identified new compounds that likely represented an additional precursor and degradation products of pulcherriminic acid and/or pulcherrimin. All of these compounds were identified in the wildtype and complemented strain, but were undetectable in the pigmentlesssnf2mutant strain. These results thus identifySNF2as a regulator of antifungal activity and pulcherriminic acid biosynthesis inM. pulcherrimaand provide a starting point for deciphering the molecular functions underlying the antagonistic activity of this yeast.Significance statementMetschnikowia pulcherrimais a strongly antifungal yeast and a most promising species for the control of notorious plant diseases. This multidisciplinary study on theM. pulcherrimamode of action compared a wildtype isolate with a pigmentless mutant exhibiting reduced antifungal activity. The transcriptional regulator Snf2 was identified as a “biocontrol regulator” controlling antifungal activity ofM. pulcherrimaviaPULgene transcription, cyclodipeptide synthesis and additional, yet uncharacterized mechanisms. The identification of cyclo(Leu-Leu), pulcherriminic acid, as well as novel precursor and degradation products of pulcherrimin, opens up new avenues for research on the metabolism and functions of pulcherrimin. Overall, this works establishesM. pulcherrimaas a genetically tractable model and will benefit the development of biocontrol solutions for important plant diseases.