bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein expression of prenyltransferase subunits in postmortem schizophrenia dorsolateral prefrontal cortex
Authors: Pinner Anita L. , Mueller Toni M. , Alganem Khaled , McCullumsmith Robert , Meador-Woodruff James H. 
Published: June 2019

AbstractThe pathophysiology of schizophrenia includes altered neurotransmission, dysregulated intracellular signaling pathway activity, and abnormal dendritic morphology that contribute to deficits of synaptic plasticity in the disorder. These processes all require dynamic protein-protein interactions at cell membranes. Lipid modifications target proteins to membranes by increasing substrate hydrophobicity by the addition of a fatty acid or isoprenyl moiety, and recent evidence suggests that dysregulated post-translational lipid modifications may play a role in multiple neuropsychiatric disorders including schizophrenia. Consistent with these emerging findings, we have recently reported decreased protein S-palmitoylation in schizophrenia. Protein prenylation is a lipid modification that occurs upstream of S-palmitoylation on many protein substrates, facilitating membrane localization and activity of key intracellular signaling proteins. Accordingly, we hypothesized that in addition to palmitoylation, protein prenylation may be abnormal in schizophrenia. To test this, we assayed protein expression of the five prenyltransferase subunits (FNTA, FNTB, PGGT1B, RABGGTA, and RABGGTB) in postmortem dorsolateral prefrontal cortex from patients with schizophrenia and paired comparison subjects (N = 13 pairs). We found decreased levels of FNTA (14%), PGGT1B (13%), and RABGGTB (8%) in schizophrenia. To determine if upstream or downstream factors may be driving these changes, we also assayed protein expression of the isoprenoid synthases FDPS and GGPS1, and prenylation-dependent processing enzymes REC and ICMT. We found these upstream and downstream enzymes to have normal protein expression. To rule out effects from chronic antipsychotic treatment, we assayed FNTA, PGGT1B and RABGGTB in cortex from rats treated long-term with haloperidol decanoate, and found no change in the expression of these proteins. Given the role prenylation plays in localization of key signaling proteins found at the synapse, these data offer a potential mechanism underlying abnormal protein-protein interactions and protein localization in schizophrenia.
Layer 6 ensembles can selectively regulate the behavioral impact and layer-specific representation of sensory deviants
Authors: Voigts Jakob , Deister Christopher A , Moore Christopher I 
Published: June 2019

AbstractPredictive models can enhance the salience of unanticipated input, and the neocortical laminar architecture is believed to be central to this computation. Here, we examined the role of a key potential node in model formation, layer (L) 6, using behavioral, electrophysiological and imaging methods in mouse somatosensory cortex. To test the contribution of L6, we applied weak optogenetic drive that changed which L6 neurons were sensory-responsive, without affecting overall firing rates in L6 or L2/3. This stimulation suppressed L2/3 deviance encoding, but maintained other stimulus encoding. The stimulation also selectively suppressed behavioral sensitivity to deviant stimuli without impacting baseline performance. In contrast, stronger L6 drive inhibited firing and suppressed overall sensory function. These findings indicate that, despite their sparse activity, specific ensembles of stimulus-driven L6 neurons are required to form neocortical predictions, and for their behavioral benefit.
Selective Activation of TASK-3-containing K+ Channels Reveals Their Therapeutic Potentials in Analgesia
Authors: Liao Ping , Qiu Yunguang , Mo Yiqing , Fu Jie , Song Zhenpeng , Huang Lu , Bai Suwen , Wang Yang , Zhu Jia-Jie , Tian Fuyun , Chen Zhuo , Pan Nanfang , Sun Er-Yi , Yang Linghui , Lan Xi , Chen Yinbin , Huang Dongping , Sun Peihua , Zhao Lifen , Yang Dehua , Lu Weiqiang , Yang Tingting , Xiao Junjie , Li Wei-Guang , Gao Zhaobing , Shen Bing , Zhang Qiansen , Liu Jin , Jiang Hualiang , Jiang Ruotian , Yang Huaiyu 
Published: June 2019

ABSTRACTThe paucity of selective agonists for TASK-3, a member of two-pore domain K+ (K2P) channels, has contributed to our limited understanding of its biological functions. By targeting a novel druggable transmembrane cavity using a structure-based drug design approach, we discovered a biguanide compound, CHET3, as a highly selective allosteric activator for TASK-3-containing K2P channels, including TASK-3 homomer and TASK-3/TASK-1 heteromer. CHET3 displayed unexpectedly potent analgesic effects in vivo in a variety of acute and chronic pain models in rodents that could be abolished by pharmacology or genetic ablation of TASK-3. We further found that TASK-3-containing channels anatomically define a unique subset population of small-sized, TRPM8, TRPV1 or tyrosine hydroxylase-positive nociceptive sensory neurons and functionally regulate their membrane excitability, supporting CHET3 analgesia in thermal hyperalgesia and mechanical allodynia under chronic pain. Overall, our proof-of-concept study reveals TASK-3-containing K2P channels as a novel druggable target for treating pain.One Sentence SummaryIdentification of a novel drug target and its new hit compounds for developing new-generation non-opioid analgesics.
NADH dehydrogenases contribute to extracellular electron transfer byShewanella oneidensisMR-1 in bioelectrochemical systems
Authors: Madsen Cody S. , TerAvest Michaela A. 
Published: June 2019

AbstractShewanella oneidensisMR-1 is quickly becoming a synthetic biology workhorse for bioelectrochemical technologies due to a high level of understanding of its interaction with electrodes. Transmembrane electron transfer via the Mtr pathway has been well characterized, however, the role of NADH dehydrogenases in feeding electrons to Mtr has been only minimally studied inS. oneidensisMR-1. Four NADH dehydrogenases are encoded in the genome, suggesting significant metabolic flexibility in oxidizing NADH under a variety of conditions. Strains containing in-frame deletions of each of these dehydrogenases were grown in anodic bioelectrochemical systems with N-acetylglucosamine or D,L-lactate as the carbon source to determine impact on extracellular electron transfer. A strain lacking the two dehydrogenases essential for aerobic growth exhibited a severe growth defect with an anode (+0.4 VSHE) or Fe(III)-NTA as the terminal electron acceptor. Our study reveals that the same NADH dehydrogenase complexes are utilized under oxic conditions or with a high potential anode. Understanding the role of NADH in extracellular electron transfer may help improve biosensors and give insight into other applications for bioelectrochemical systems.TOC Graphic
Augmenting biologging with supervised machine learning to studyin situbehavior of the medusaChrysaora fuscescens
Authors: Fannjiang Clara , Mooney T. Aran , Cones Seth , Mann David , Alex Shorter K. , Katija Kakani 
Published: June 2019

AbstractZooplankton occupy critical roles in marine ecosystems, yet their fine-scale behavior remains poorly understood due to the difficulty of studying individualsin situ. Here we combine biologging with supervised machine learning (ML) to demonstrate a pipeline for studyingin situbehavior of larger zooplankton such as jellyfish. We deployed the ITAG, a biologging package with high-resolution motion sensors designed for soft-bodied invertebrates, on 8Chrysaora fuscescensin Monterey Bay, using the tether method for retrieval. Using simultaneous video footage of the tagged jellyfish, we develop ML methods to 1) identify periods of tag data corrupted by the tether method, which may have compromised prior research findings, and 2) classify jellyfish behaviors. Our tools yield characterizations of fine-scale jellyfish activity and orientation over long durations, and provide evidence that developing behavioral classifiers onin siturather than laboratory data is essential.Summary StatementHigh-resolution motion sensors paired with supervised machine learning can be used to infer fine-scalein situbehavior of zooplankton for long durations.
Biased competition in semantic representation during natural visual search
Authors: Shahdloo Mohammad , Çelik Emin , Çukur Tolga 
Published: June 2019

AbstractHumans divide their attention among multiple visual targets in daily life, and visual search gets more difficult as the number of targets increases. The biased competition hypothesis (BC) has been put forth as an explanation for this phenomenon. BC suggests that brain responses during divided attention are a weighted linear combination of the responses during search for each target individually. Furthermore, this combination is biased by the intrinsic selectivity of cortical regions. Yet, it is unknown whether attentional modulations of semantic representations of cluttered and dynamic natural scenes are consistent with this hypothesis. Here, we investigated whether BC accounts for semantic representation during natural category-based visual search. Human subjects viewed natural movies, and their whole-brain BOLD responses were recorded while they attended to “humans”, “vehicles” (i.e. single-target attention tasks), or “both humans and vehicles” (i.e. divided attention) in separate runs. We computed a voxelwise linearity index to assess whether semantic representation during divided attention can be modeled as a weighted combination of representations during the two single-target attention tasks. We then examined the bias in weights of this linear combination across cortical ROIs. We find that semantic representations during divided attention are linear to a substantial degree, and that they are biased toward the preferred target in category-selective areas across ventral temporal cortex. Taken together, these results suggest that the biased competition hypothesis is a compelling account for attentional modulations of semantic representation across cortex.Significance StatementNatural vision is a complex task that involves splitting attention between multiple search targets. According to the biased competition hypothesis (BC), limited representational capacity of the cortex inevitably leads to a competition among representation of these targets and the competition is biased by intrinsic selectivity of cortical areas. Here we examined BC for semantic representation of hundreds of object and action categories in natural movies. We observed that: 1) semantic representation during simultaneous attention to two object categories is a weighted linear combination of representations during attention to each of them alone, and 2) the linear combination is biased toward semantic representation of the preferred object category in strongly category-selective areas. These findings suggest BC as a compelling account for attentional modulations of semantic representation across cortex in natural vision.
Experience- and sex-dependent intrinsic plasticity in the zebra finch auditory cortex during song memorization
Authors: Chen Andrew N , Meliza C Daniel 
Published: June 2019

AbstractEarly auditory experience is critical to the development of vocal communication. Zebra finches and other songbirds have a sensitive period when young birds memorize a song to use as a model for vocal production. We found that intrinsic spiking dynamics change dramatically during this period in the caudal mesopallium, a cortical-level auditory area. Specifically, the proportion of neurons that only fire transiently at the onset of intracellular current injections increases, along with Kv1.1, a channel that facilitates transient spiking. Plasticity is greater in males and requires exposure to a complex, noisy environment. These observations indicate that intrinsic dynamics are modulated in response to the acoustic environment to support robust auditory processing during a critical phase of vocal learning.
Interdependence of balance mechanisms during bipedal locomotion
Authors: Fettrow Tyler , Reimann Hendrik , Grenet David , Thompson Elizabeth , Crenshaw Jeremy , Higginson Jill , Jeka John 
Published: June 2019

AbstractOur main interest is to identify how humans maintain upright while walking. Balance during standing and walking is different, primarily due to a gait cycle which the nervous system must contend with a variety of body configurations and frequent perturbations (i.e., heel-strike). We have identified three mechanisms that healthy young adults use to respond to a visually perceived fall to the side. The lateral ankle mechanism and the foot placement mechanism are used to shift the center of pressure in the direction of the perceived fall, and the center of mass away from the perceived fall. The push-off mechanism, a systematic change in ankle plan-tarflexion angle in the trailing leg, results in fine adjustments to medial-lateral balance near the end of double stance. The focus here is to understand how the three basic balance mechanisms are coordinated to produce an overall balance response. The results indicate that lateral ankle and foot placement mechanisms are inversely related. Larger lateral ankle responses lead to smaller foot placement changes. Correlations involving the push-off mechanism, while significant, were weak. However, the consistency of the correlations across stimulus conditions suggest the push-off mechanism has the role of small adjustments to medial-lateral movement near the end of the balance response. This verifies that a fundamental feature of human bipedal gait is a highly flexible balance system that recruits and coordinates multiple mechanisms to maintain upright balance during walking to accommodate extreme changes in body configuration and frequent perturbations.
NOISYmputer: genotype imputation in bi-parental populations for noisy low-coverage next-generation sequencing data
Authors: Lorieux Mathias , Gkanogiannis Anestis , Fragoso Christopher , Rami Jean-François 
Published: June 2019

AbstractMotivationLow-coverage next-generation sequencing (LC-NGS) methods can be used to genotype bi-parental populations. This approach allows the creation of highly saturated genetic maps at reasonable cost, precisely localized recombination breakpoints, and minimize mapping intervals for quantitative-trait locus analysis.The main issues with these genotyping methods are (1) poor performance at heterozygous loci, (2) a high percentage of missing data, (3) local errors due to erroneous mapping of sequencing reads and reference genome mistakes, and (4) global, technical errors inherent to NGS itself.Recent methods like Tassel-FSFHap or LB-Impute are excellent at addressing issues 1 and 2, but nonetheless perform poorly when issues 3 and 4 are persistent in a dataset (i.e. “noisy” data). Here, we present an algorithm for imputation of LC-NGS data that eliminates the need of complex pre-filtering of noisy data, accurately types heterozygous chromosomic regions, corrects erroneous data, and imputes missing data. We compare its performance with Tassel-FSFHap, LB-Impute, and Genotype-Corrector using simulated data and three real datasets: a rice single seed descent (SSD) population genotyped by genotyping by sequencing (GBS) by whole genome sequencing (WGS), and a sorghum SSD population genotyped by GBS.AvailabilityNOISYmputer, a Microsoft Excel-Visual Basic for Applications program that implements the algorithm, is available at mapdisto.free.fr. It runs in Apple macOS and Microsoft Windows operating systems.Supplementary files: Download link
Integrative Network Analysis of Differentially Methylated and Expressed Genes for Biomarker Identification in Leukemia
Authors: Sanchez Robersy , Mackenzie Sally A. 
Published: June 2019

AbstractGenome-wide DNA methylation and gene expression are commonly altered in pediatric acute lymphoblastic leukemia (PALL). Integrated analysis of cytosine methylation and expression datasets has the potential to provide deeper insights into the complex disease states and their causes than individual disconnected analyses. Studies of protein-protein interaction (PPI) networks of differentially methylated (DMGs) and expressed genes (DEGs) showed that gene expression and methylation consistently targeted the same gene pathways associated with cancer:Pathways in cancer, Ras signaling pathway, PI3K-Akt signaling pathway, andRap1 signaling pathway, among others. Detected gene hubs and hub sub-networks are integrated by signature loci associated with cancer that include, for example,NOTCH1, RAC1, PIK3CD, BCL2, andEGFR. Statistical analysis disclosed a stochastic deterministic dependence between methylation and gene expression within the set of genes simultaneously identified as DEGs and DMGs, where larger values of gene expression changes are probabilistically associated with larger values of methylation changes. Concordance analysis of the overlap between enriched pathways in DEG and DMG datasets revealed statistically significant agreement between gene expression and methylation changes, reflecting a coordinated response of methylation and gene-expression regulatory systems. These results support the identification of reliable and stable biomarkers for cancer diagnosis and prognosis.
Structural and functional brain parameters related to cognitive performance across development: Replication and extension of the parieto-frontal integration theory in a single sample
Authors: Gur Ruben C. , Butler Ellyn R. , Moore Tyler M. , Rosen Adon F.G. , Ruparel Kosha , Satterthwaite Theodore D. , Roalf David R. , Gennatas Efstathios D. , Bilker Warren B. , Shinohara Russell T. , Port Allison , Elliott Mark A. , Verma Ragini , Davatzikos Christos , Wolf Daniel H. , Detre John A. , Gur Raquel E. 
Published: June 2019

AbstractThe Parieto-Frontal Integration Theory (PFIT) identified a fronto-parietal network of regions where individual differences in brain parameters most strongly relate to cognitive performance. PFIT was supported and extended in adult samples, but not in youths or within single-scanner well-powered multimodal studies. We performed multimodal neuroimaging in 1601 youths age 8-22 on the same 3-Tesla scanner with contemporaneous neurocognitive assessment, measuring volume, gray matter density (GMD), mean diffusivity (MD), cerebral blood flow (CBF), resting-state functional MRI measures of amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo), and activation to a working memory and a social cognition task. Across age and sex groups, better performance was associated with higher volumes, greater GMD, lower MD, lower CBF, higher ALFF and ReHo and greater activation for the working memory task in PFIT regions. However, additional cortical, striatal, limbic and cerebellar regions showed comparable effects, hence PFIT needs expansion into an Extended PFIT (ExtPFIT) network incorporating nodes that support motivation and affect. Associations of brain parameters became stronger with advancing age group from childhood to adolescence to young adulthood, effects occurring earlier in females. This ExtPFIT network is developmentally fine-tuned, optimizing abundance and integrity of neural tissue while maintaining low resting energy state.
An improved plant toolset for high-throughput recombineering
Authors: Brumos J. , Zhao C. , Gong Y. , Soriano D. , Patel A.P. , Perez-Amador M.A. , Stepanova A.N. , Alonso J.M 
Published: June 2019

AbstractGene functional studies often rely on the expression of a gene of interest as transcriptional and translational fusions with specialized tags. Ideally, this is done in the native chromosomal contexts to avoid potential misexpression artifacts. Although recent improvements in genome editing make it possible to directly modify the target genes in their native chromosomal location, classical transgenesis is still the preferred experimental approach chosen in most gene tagging studies because of its time efficiency and accessibility. We have developed a recombineering-based tagging system that brings together the convenience of the classical transgenic approaches and the high degree of confidence in the obtained results provided by the direct chromosomal tagging achievable by genome editing strategies. These simple and customizable recombineering toolsets and protocols allow for high-throughput generation of a variety of genetic modifications. In addition, a highly efficient recombinase-mediated cassette exchange system has been developed to facilitate the transfer of the desired sequences from a BAC clone to a transformation-compatible binary vector, expanding the use of the recombineering approaches beyond Arabidopsis. The utility of this system is demonstrated by the generation of over 250 whole-gene translational fusions and 123 Arabidopsis transgenic lines corresponding to 62 auxin-related genes, and the characterization of the translational reporter expression patterns for 14 auxin biosynthesis genes.
Recounting the FANTOM Cage Associated Transcriptome
Authors: Imada Eddie-Luidy , Sanchez Diego Fernando , Collado-Torres Leonardo , Wilks Christopher , Matam Tejasvi , Dinalankara Wikum , Stupnikov Aleksey , Lobo-Pereira Francisco , Yip Chi-Wai , Yasuzawa Kayoko , Kondo Naoto , Itoh Masayoshi , Suzuki Harukazu , Kasukawa Takeya , Hon Chung-Chau , de Hoon Michiel JL , Shin Jay W , Carninci Piero ,   FANTOM consortium, Jaffe Andrew E , Leek Jeffrey T , Favorov Alexander , Franco Gloria R , Langmead Ben , Marchionni Luigi 
Published: June 2019

ABSTRACTLong non-coding RNAs (lncRNAs) have emerged as key coordinators of biological and cellular processes. Characterizing lncRNA expression across cells and tissues is key to understanding their role in determining phenotypes including human diseases. We present hereFC-R2, a comprehensive expression atlas across a broadly-defined human transcriptome, inclusive of over 109,000 coding and non-coding genes, as described in the FANTOM CAGE-Associated Transcriptome (FANTOM-CAT) study. This atlas greatly extends the gene annotation used in the originalrecount2resource. We demonstrate the utility of theFC-R2atlas by reproducing key findings from published large studies and by generating new results across normal and diseased human samples. In particular, we (a) identify tissue specific transcription profiles for distinct classes of coding and non-coding genes, (b) perform differential expression analyses across thirteen cancer types, providing new insights linking promoter and enhancer lncRNAs expression to tumor pathogenesis, and (c) confirm the prognostic value of several enhancers in cancer. Comprised of over 70,000 samples, theFC-R2atlas will empower other researchers to investigate functions and biological roles of both known coding genes and novel lncRNAs. Most importantly, access to theFC-R2atlas is available fromhttps://jhubiostatistics.shinyapps.io/recount/, therecountBioconductor package, andhttp://marchionnilab.org/fcr2.html.
The frequency of cortical microstimulation shapes artificial touch
Authors: Callier Thierri , Brantly Nathan , Caravelli Attilio , Bensmaia Sliman J. 
Published: June 2019

AbstractIntracortical microstimulation (ICMS) of somatosensory cortex evokes vivid tactile sensations and can be used to convey sensory feedback in brain-controlled bionic hands. Changes in ICMS frequency result in discriminable percepts, but the effects of frequency have only been investigated over a narrow range of low frequencies, spanning only a small fraction of that relevant for neuroprosthetics. Furthermore, the sensory correlates of changes in ICMS frequency remain to be elucidated. To fill these gaps, we trained monkeys to discriminate the frequency of ICMS pulse trains over a wide range of frequencies (from 10 to 400 Hz). ICMS amplitude also varied across stimuli to reduce the animals’ reliance on magnitude in making frequency judgments. We found that animals could discriminate ICMS frequency up to about 200 Hz but that the sensory correlates of frequency were highly electrode dependent. We discuss the implications of our findings for neural coding and brain-machine interfaces.