bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinguishing “self” from “other” in a dynamic synchronization task with an adaptive virtual partner
Authors: Fairhurst Merle T. , Janata Petr , Keller Peter E. 
Published: May 2019

AbstractFor precise interpersonal coordination, some degree of merging a sense of self with other is required. In group music making, one may want to be in “sync” with one’s ensemble and, if playing a similar instrument, one can assume a degree of temporal and acoustic overlap. However, to what extent is self-other merging optimal? An incorrect balance of segregation and integration of self and other information would result in a lack of interpersonal cohesion or a disruption of self-agency. Using an interactive finger-tapping task with a virtual partner and functional MRI, we explored neural differences between self-other merging and distinction. Varying both the level of adaptivity of a virtual partner and the quality of self-related auditory feedback, we show that the predictability of the other and availability of distinguishable, self-related information improve performance and demonstrate how dynamic interactions vary one’s sense of agency. From neuroimaging data, we identify regions that are more active when self and other are distinct, including the TPJ. Conversely, we observe activity in the cerebellum, EBA and SMA when self and other blur. These findings suggest that a certain degree of self-other distinction at sensorimotor, experiential, and neurophysiological levels is required to maintain successful interpersonal coordination.
Insights about variation in meiosis from 31,228 human sperm genomes
Authors: Bell Avery Davis , Mello Curtis J. , Nemesh James , Brumbaugh Sara A. , Wysoker Alec , McCarroll Steven A. 
Published: May 2019

AbstractMeiosis, while critical for reproduction, is also highly variable and error prone: crossover rates vary among humans and individual gametes, and chromosome nondisjunction leads to aneuploidy, a leading cause of miscarriage. To study variation in meiotic outcomes within and across individuals, we developed a way to sequence many individual sperm genomes at once. We used this method to sequence the genomes of 31,228 gametes from 20 sperm donors, identifying 813,122 crossovers, 787 aneuploid chromosomes, and unexpected genomic anomalies. Different sperm donors varied four-fold in the frequency of aneuploid sperm, and aneuploid chromosomes gained in meiosis I had 36% fewer crossovers than corresponding non-aneuploid chromosomes. Diverse recombination phenotypes were surprisingly coordinated: donors with high average crossover rates also made a larger fraction of their crossovers in centromere-proximal regions and placed their crossovers closer together. These same relationships were also evident in the variation among individual gametes from the same donor: sperm with more crossovers tended to have made crossovers closer together and in centromere-proximal regions. Variation in the physical compaction of chromosomes could help explain this coordination of meiotic variation across chromosomes, gametes, and individuals.
An Electrophysiological Marker of Arousal Level in Humans
Authors: Lendner Janna D. , Helfrich Randolph F. , Mander Bryce A. , Romundstad Luis , Lin Jack J. , Walker Matthew P. , Larsson Pal G. , Knight Robert T. 
Published: May 2019

AbstractDeep non-rapid eye movement sleep (NREM) – also called slow wave sleep (SWS) – and general anesthesia are prominent states of reduced arousal linked to the occurrence of slow oscillations in the electroencephalogram (EEG). Rapid eye movement (REM) sleep, however, is also associated with a diminished arousal level, but is characterized by a desynchronized, ‘wake-like’ EEG. This observation challenges the notion of oscillations as the main physiological mediator of reduced arousal. Using intracranial and surface EEG recordings in four independent data sets, we establish the 1/f spectral slope as an electrophysiological marker that accurately delineates wakefulness from anesthesia, SWS and REM sleep. The spectral slope reflects the non-oscillatory, scale-free measure of neural activity and has been proposed to index the local balance between excitation and inhibition. Taken together, these findings reconcile the long-standing paradox of reduced arousal in both REM and NREM sleep and provide a common unifying physiological principle — a shift in local Excitation/ Inhibition balance — to explain states of reduced arousal such as sleep and anesthesia in humans.Significance StatementThe clinical assessment of arousal levels in humans depends on subjective measures such as responsiveness to verbal commands. While non-rapid eye movement (NREM) sleep and general anesthesia share some electrophysiological markers, rapid eye movement sleep (REM) is characterized by a ‘wake-like’ electroencephalogram. Here, we demonstrate that non-oscillatory, scale-free electrical brain activity — recorded from both scalp electroencephalogram and intracranial recordings in humans — reliably tracks arousal levels during both NREM and REM sleep as well as under general anesthesia with propofol. Our findings suggest that non-oscillatory brain activity can be used effectively to monitor vigilance states.
Regulated spindle orientation buffers tissue growth in the epidermis
Authors: Morrow Angel , Underwood Julie , Seldin Lindsey , Hinnant Taylor , Lechler Terry 
Published: May 2019

SummaryTissue homeostasis requires a balance between progenitor cell proliferation and loss. Mechanisms that maintain this robust balance are needed to avoid tissue loss or overgrowth. Here we demonstrate that regulation of spindle orientation/asymmetric cell divisions is one mechanism that is used to buffer changes in proliferation and tissue turnover in mammalian skin. Genetic and pharmacologic experiments demonstrate that asymmetric cell divisions were increased in hyperproliferative conditions and decreased under hypoproliferative conditions. Further, active K-Ras also increased the frequency of asymmetric cell divisions. Disruption of spindle orientation in combination with constitutively active K-Ras resulted in massive tissue overgrowth. Together, these data highlight the essential roles of spindle orientation in buffering tissue homeostasis in response to perturbations.
Transcriptomic networks implicate neuronal energetic abnormalities in three mouse models harboring autism and schizophrenia-associated mutations
Authors: Gordon Aaron , Grønborg-Forsingdal Annika , Klewe Ib Vestergaard , Nielsen Jacob , Didriksen Michael , Werge Thomas , Geschwind Daniel 
Published: May 2019

AbstractGenetic risk for psychiatric illness is complex, so identification of shared molecular pathways where distinct forms of genetic risk might coincide is of substantial interest. A growing body of genetic and genomic studies suggest that such shared molecular pathways exist across disorders with different clinical presentations, such as schizophrenia and autism spectrum disorder (ASD). But how this relates to specific genetic risk factors is unknown. Further, whether some of the molecular changes identified in brain relate to potentially confounding antemortem or post-mortem factors is difficult to prove. We analyzed the transcriptome from the cortex and hippocampus of three mouse lines modeling human copy number variants (CNVs) associated with schizophrenia and ASD: Df(h15q13)/+, Df(h22q11)/+, and Df(h1q21)/+ which carry the 15q13.3 deletion, 22q11.2 deletion, and 1q21.1 deletion, respectively. Although we found very little overlap of differential expression at the level of individual genes, gene network analysis identified two modules of co-expressed genes that were dysregulated across all three mouse models. One module observed in both cortex and hippocampus was associated with neuronal energetics and firing rate, and overlapped with changes identified in post mortem human brain from SCZ and ASD patients. These data highlight aspects of convergent gene expression in mouse models harboring major risk alleles, and strengthen the connection between neuronal energetic dysfunction and neuropsychiatric disorders in humans.
Massively parallel reporter assays combined with cell-type specific eQTL informed multiple melanoma loci and identified a pleiotropic function of HIV-1 restriction gene,MX2, in melanoma promotion
Authors: Choi Jiyeon , Zhang Tongwu , Vu Andrew , Ablain Julien , Makowski Matthew M , Colli Leandro M , Xu Mai , Rothschild Harriet , Gräwe Cathrin , Kovacs Michael A , Brossard Myriam , Taylor John , Pasaniuc Bogdan , Chari Raj , Chanock Stephen J , Hoggart Clive J , Demenais Florence , Barrett Jennifer H , Law Matthew H , Iles Mark M , Yu Kai , Vermeulen Michiel , Zon Leonard I , Brown Kevin M 
Published: May 2019

AbstractGenome-wide association studies (GWAS) have identified ∼20 melanoma susceptibility loci. To identify susceptibility genes and variants simultaneously from multiple GWAS loci, we integrated massively-parallel reporter assays (MPRA) with cell type-specific epigenomic data as well as melanocyte-specific expression quantitative trait loci (eQTL) profiling. Starting from 16 melanoma loci, we selected 832 variants overlapping active regions of chromatin in cells of melanocytic lineage and identified 39 candidate functional variants displaying allelic transcriptional activity by MPRA. For four of these loci, we further identified four colocalizing melanocytecis-eQTL genes (CTSS,CASP8,MX2, andMAFF) matching the allelic activity of MPRA functional variants. Among these, we further characterized the locus encompassing the HIV-1 restriction gene,MX2, on chromosome band Chr21q22.3 and validated a functional variant, rs398206, among multiple high LD variants. rs398206 mediates allelic transcriptional activity via binding of the transcription factor, YY1. This allelic transcriptional regulation is consistent with a significantcis-eQTL ofMX2in primary human melanocytes, where the melanoma risk-associated A allele of rs398206 is correlated with higherMX2levels. Melanocyte-specific transgenic expression of humanMX2in a zebrafish model demonstrated accelerated melanoma formation in aBRAFV600Ebackground. Thus, using an efficient scalable approach to streamline GWAS follow-up functional studies, we identified multiple candidate melanoma susceptibility genes and variants, and uncovered a pleiotropic function ofMX2in melanoma susceptibility.
Copper Blocks V-ATPase Activity and SNARE Complex Formation to Inhibit Yeast Vacuole Fusion
Authors: Miner Gregory E. , Sullivan Katherine D. , Zhang Chi , Hurst Logan R. , Starr Matthew L. , Rivera-Kohr David A. , Jones Brandon C. , Guo Annie , Fratti Rutilio A. 
Published: May 2019

ABSTRACTThe accumulation of Copper in organisms can lead to altered functions of various pathways, and become cytotoxic through the generation of reactive oxygen species. In yeast, cytotoxic metals such as Hg+, Cd2+, and Cu2+are transported into the lumen of the vacuole through various pumps. Copper ions are initially transported into the cell by the copper transporter Ctr1 at the plasma membrane and sequestered by chaperones and other factors to prevent cellular damage by free cations. Excess copper ions can subsequently be transported into the vacuole lumen by an unknown mechanism. Transport across membranes requires the reduction of Cu2+to Cu+. Labile copper ions can interact with membranes to alter fluidity, lateral phase separation and fusion. Here we found that CuCl2potently inhibited vacuole fusion by blocking SNARE pairing. This was accompanied by the inhibition of V-ATPase H+pumping. Deletion of the vacuolar reductase Fre6 had no effect on the inhibition of fusion by copper. This suggests that that Cu2+is responsible for the inhibition of vacuole fusion and V-ATPase function. This notion is supported by the differential effects chelators. The Cu2+-specific chelator TETA rescued fusion, whereas the Cu+-specific chelator BCS had no effect on the inhibited fusion.
Machine Learning Prediction of Incidence of Alzheimer’s Disease Using Large-Scale Administrative Health Data
Authors: Park Ji Hwan , Cho Han Eol , Kim Jong Hun , Wall Melanie , Stern Yaakov , Lim Hyunsun , Yoo Shinjae , Kim Hyoung Seop , Cha Jiook 
Published: May 2019

AbstractNationwide population-based cohort provides a new opportunity to build a completely automated risk prediction model based on individuals’ history of health and healthcare beyond existing risk prediction models. We tested the possibility of machine learning models to predict future incidence of Alzheimer’s disease (AD) using large-scale administrative health data. From the Korean National Health Insurance Service database between 2002 and 2010, we obtained de-identified health data in elders above 65 years (N=40,736) containing 4,894 unique clinical features including ICD-10 codes, medication codes, laboratory values, history of personal and family illness, and socio-demographics. To define incident AD two operational definitions were considered: “definite AD” with diagnostic codes and dementia medication (n=614) and “probable AD” with only diagnosis (n=2,026). We trained and validated a random forest, support vector machine, and logistic regression to predict incident AD in 1,2,3, and 4 subsequent years. For predicting future incidence of AD in balanced samples (bootstrapping), the machine learning models showed reasonable performance in 1-year prediction with AUC of 0.775 and 0.759, based on “definite AD” and “probable AD” outcomes, respectively; in 2-year, 0.730 and 0.693; in 3-year, 0.677 and 0.644; in 4-year, 0.725 and 0.683. The results were similar when the entire (unbalanced) samples were used. Important clinical features selected in logistic regression included hemoglobin level, age, and urine protein level. This study may shed a light on the utility of the data-driven machine learning model based on large-scale administrative health data in AD risk prediction, which may enable better selection of individuals at risk for AD in clinical trials or early detection in clinical settings.
Generation of transgenic quails by in vivo transfection of primordial germ cells
Authors: Serralbo Olivier , Véron Nadège , Cooper Caitlin , Dejardin Marie-Julie , Doran Timothy , Marcelle Christophe 
Published: May 2019

AbstractDuring development, dynamic changes in tissue shapes known as morphogenesis result from the exquisite orchestration of signalling pathways, cell–cell interactions, cell divisions, and coordinated movements. How cells within embryos adopt a vast array of cell fates and tissue shapes in such an ever-changing environment has fascinated scientists for generations, yet the ability to observe and characterize those rapid changes has proven technically challenging in higher vertebrates. The japanese quail (Coturnix coturnix japonica) is an attractive model where basic rules driving morphogenesis in amniotes can be deciphered using genetic approaches. Similar to the more popular chicken model, the quail embryo is easily accessible to a wide range of manipulations and live imaging. A decisive asset of quail over chicken is a much shorter life cycle, which makes its use as genetic model for basic research extremely appealing. To date, all existing transgenic quail lines were generated using replication-deficient lentiviruses, but diverse limitations of this approach have hindered the widespread expansion of such technology. Here, we successfully used a plasmid-based in vivo transfection of quail primordial germ cells (PGCs) to generate a number of transgenic quail lines over a short period of time. The plasmid-based approach is simple, efficient and it allows using the infinite variety of genome engineering approaches developed in other models, such as strategies to facilitate transgenic bird selection, shown here. This major technological development completes the vast panel of techniques applicable to the avian model, making it one of the most versatile experimental systems available.
Knocking out non-muscle myosin II in retinal ganglion cells promotes long-distance optic nerve regeneration
Authors: Wang Xue-Wei , Yang Shu-Guang , Zhang Chi , Ma Jin-Jin , Zhang Yingchi , Yang Bin-Bin , Weng Yi-Lan , Ming Guo-Li , Kosanam Anish R. , Saijilafu  , Zhou Feng-Quan 
Published: May 2019

AbstractIn addition to altered gene expression, pathological cytoskeletal dynamics in the axon are another key intrinsic barrier for axon regeneration in the central nervous system (CNS). Here we showed that knocking out myosin IIA/B in retinal ganglion cells alone either before or after optic nerve crush induced marked and sustained optic nerve regeneration. Combined Lin28 overexpression and myosin IIA/B knockout led to synergistic promoting effect and long-distance axon regeneration. Immunostaining, RNA-seq and western blot analyses revealed that myosin II deletion did not affect known axon regeneration signaling pathways or the expression of regeneration associated genes. Instead, it abolished the retraction bulb formation and significantly enhanced the axon extension efficiency. The study provided clear evidence that directly targeting neuronal cytoskeleton was sufficient to induce strong CNS axon regeneration, and combining gene expression in the soma and modified cytoskeletal dynamics in the axon was a promising approach for long-distance CNS axon regeneration.
C1orf109L promote R-loop accumulation induced DNA damage to inhibit cell growth
Authors: Peng Dou , Yiqun Li , Wanqiu Xie , Xiaoqing Zhang , Dandan Zhang , Yanpeng Ci , Xiaohan Zhang , Shupei Qiao , Akhtar Muhammad Luqman , Fang Han , Li Yu 
Published: May 2019

AbstractAs a function unknown gene, C1orf109 is lower expression in various cells. Here, we reported that C1orf109L, the longest variant of C1orf109, which interacted with R-loop-regulating proteins to trigger R-loop, a three-stranded nucleic acid structure frequently mediated genome instability, accumulation. C1orf109L induce chronic DNA damage to promote P21 upregulation and strongly inhibits cell growth in vitro and in vivo by arresting the cell cycle in the G2 phase. With camptothecin (CPT), an R-loop activator, treatment, C1orf109L further triggers R-loop accumulation-induced DNA damage and promotes cell death by activating cell-death pathway. Furthermore, CPT treatment increases C1orf109L ubiquitination and turnover, which inhibits cell death and promotes the G0/G1 phase of the cell cycle. Therefore, our data illustrated the mechanisms underlying C1orf109L-related cell growth inhibition and provide feasibility and limitations for C1orf109L as a potential target for cancer therapy.
The memory of hyperosmotic stress response in yeast is modulated by gene-positioning
Authors: Ben Meriem Zacchari , Khalil Yasmine , Hersen Pascal , Fabre Emmanuelle 
Published: May 2019

AbstractCellular memory is a critical ability displayed by microorganisms in order to adapt to potentially detrimental environmental fluctuations. In the unicellular eukaryoteS. cerevisiaecellular memory can take the form of a faster or a decreased response following repeated stresses in cell population. Using microfluidics and fluorescence time-lapse microscopy, we studied how yeasts respond to short-pulsed hyperosmotic stresses at the single-cell level by analyzing the dynamical behavior of the stress responsive STL1 promoter fused to a fluorescent reporter. We established that pSTL1 shows variability in its successive activations following two repeated short stresses. Despite this variability, most cells displayed a memory of past stresses through a decreased activity of pSTL1 upon repeated stress. Notably, we showed that genomic location is important for the memory effect since promoter displacement to a pericentromeric chromatin domain leads to a decreased transcriptional strength of pSTL1 and to the loss of memory. This study provides a quantitative description of a cellular memory that includes single-cell variability and points towards the contribution of the chromatin structure in stress memory.
Glyoxal Does Not Preserve Cellular Proteins as Accurately as PFA: A Microscopical Survey of Epitopes
Authors: Celikkan Ferda Topal , Mungan Ceren , Sucu Merve , Uysal Fatma , Kahveci Selda , Hayme Serhat , Kuscu Nilay , Ozkavukcu Sinan , Celik-Ozenci Ciler , Can Alp 
Published: May 2019

AbstractChemical fixation is one of the most critical steps to retaining cellular targets as naturally as possible. Recent developments in microscopy allow sophisticated detection and measuring techniques with which spatio-temporal molecular alterations is conceivable. Here, we document the fixation competence of glyoxal (Gly), a less-toxic dialdehyde molecule, and paraformaldehyde (PFA) side-by-side (with or without Triton-X 100 permealization) in live- and fixed-cell preparations including human stem cells, spermatozoa, mouse oocytes/embryos using super-resolution microscopy. Although Gly seemed to act faster than PFA, catastrophic consequences were found not acceptable, especially in oocytes and embryos. Due to cell lysate and immunocytochemistry surveys, it was obvious that PFA is superior to Gly in retaining cellular proteinsin situwith little/no background staining. In many samples, PFA revealed more reliable and consistent results regarding the protein quantity and cellular localization corresponding to previously defined patterns in the literature. Although the use of Gly is beneficial as indicated by previous reports, we concluded that it does not meet the requirement for proper fixation, at least for the tested cell types and proteins.
Taxonomic resolution of the ribosomal RNA operon in bacteria: Implications for its use with long read sequencing
Authors: de Oliveira Martins Leonardo , Page Andrew J. , Charles Ian G. 
Published: May 2019

AbstractLong-read sequencing technologies enable capture of the full-length of ribosomal RNA operons in a single read. Bacterial cells usually have multiple copies of this ribosomal operon; sequence variation within a species of bacterium can exceed variation between species. For uncultured organisms this may affect the overall taxonomic resolution, to genus level, of the full-length ribosomal operon.
Prevalence and distribution of antimicrobial resistance determinants ofEscherichia coliisolates obtained from meat in South Africa
Authors: Jaja Ishmael Festus , Oguttu James , Green Ezekiel , Muchenje Voster 
Published: May 2019

AbstractObjectiveThis study aimed to characterise antibiotics resistance ofEscherichia coliisolates from the formal meat sector (FMS) and informal meat sectors (INMS).MethodA total of 162 and 102E. coliisolates from the FMS, and INMS respectively were isolated by standard culture-based, and biochemical reactions. The isolates were further confirmed by polymerase chain reaction (PCR). The disc diffusion method was used to screen for antimicrobial susceptibility against 19 different antibiotics. The presence of class 1-2 integrons in eachE. coliisolates was assessed usingandregions specific primers.ResultAmong the 19 antimicrobials, resistance to tetracyclines, aminoglycosides, cephalosporins, and nitrofurans were found to be more frequent than carbapenems and phenicol with a noticeable increase in the number of multi-drug resistance ranging from three to ten antimicrobials. A total of 20 resistance determinants were assessed with their prevalence and distributions obtained as follows for FMS and INMS respectively; [aminoglycosides:aadA(40.6%; 31.9%),aacC2(21.4%; 31%),aphA1(20.8%; 15.1%),aphA2(37.7%; 18.9%) andstrA(6.5%; 9.4%)], [β-lactams:ampC(20%; 45%),blaTEM, (4.4%; 13.3), andblaZ(8.9%; 2.2%)], [Chloramphenicol:catI(1.7%; 1.7%), andcmIA1(1.7%; 1.7%)] and [tetracyclines:tetA(7.7%; 15.4%),tetB(11.5%; 24%), andtetM, (1.9%; 8.7%)], and [sulfonamides: sul1 (22.2%; 26.7%), sul2 (17.8%; 6.7%)].ConclusionMultiple antibiotic resistance (MAR) indexes ranged from 0.2 - 0.5. The results reveal a high prevalence of multidrug-resistantE. coliisolates and resistance determinants suggesting that consumers and handlers of such meat are at risk of contracting antibiotic resistantE. coli-related foodborne disease.