bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anomalies in language as a biomarker for schizophrenia
Authors: de Boer Janna N. , Brederoo Sanne G. , Voppel Alban E. , Sommer Iris E.C. 
Published: February 2020

Purpose of review
After more than a century of neuroscience research, reproducible, clinically relevant biomarkers for schizophrenia have not yet been established. This article reviews current advances in evaluating the use of language as a diagnostic or prognostic tool in schizophrenia.

Recent findings
The development of computational linguistic tools to quantify language disturbances is rapidly gaining ground in the field of schizophrenia research. Current applications are the use of semantic space models and acoustic analyses focused on phonetic markers. These features are used in machine learning models to distinguish patients with schizophrenia from healthy controls or to predict conversion to psychosis in high-risk groups, reaching accuracy scores (generally ranging from 80 to 90%) that exceed clinical raters. Other potential applications for a language biomarker in schizophrenia are monitoring of side effects, differential diagnostics and relapse prevention.

Summary
Language disturbances are a key feature of schizophrenia. Although in its early stages, the emerging field of research focused on computational linguistics suggests an important role for language analyses in the diagnosis and prognosis of schizophrenia. Spoken language as a biomarker for schizophrenia has important advantages because it can be objectively and reproducibly quantified. Furthermore, language analyses are low-cost, time efficient and noninvasive in nature.
Epigenetic immune-modulation by Histone Deacetylase Activity (HDAC) of tissue and organ regeneration inXenopus laevis
Authors: Pentagna Nathalia , dos Santos Felipe Soares , de Almeida Fernanda Martins , Abreu José Garcia , Levin Michael , Carneiro Katia 
Published: February 2020

AbstractIn the present work we propose to shed light on the epigenetic control of immune mechanisms involved duringXenopustail regeneration. Here we show that the first 24 hour post amputation (hpa), which exclusively encompasses the first wave of myeloid differentiation, are crucial to epigenetically modulate the regenerative ability ofXenopustadpoles. During this developmental window, HDAC activity was shown to be necessary for the proper establishment of myeloid cells dynamics in the regenerative bud, mainly contributing to modulate the behavior of monocytes/macrophages and neutrophils as well the mRNA expression pattern of the main myeloid markers, such as LURP, MPOX, Spib and mmp7. In addition, we functionally bridge the spatial and temporal dynamics of lipid droplets, the main platform of lipid mediators synthesis in myeloid cells during the inflammatory response, and the regenerative ability ofXenopustadpoles showing that 15-LOX activity is a key player during tail regeneration. Taken together our results support a role for the epigenetic control of inflammatory response during tissue and organ regeneration, which may positively impact translational approaches for regenerative medicine.Summary statementWe propose that Epigenetic mechanisms HDAC-dependent can control myeloid cells behavior upon tissue injury and that HDAC inhibitors may be used for tissue regeneration in translational studies.
Autism-linked Cullin3 germline haploinsufficiency impacts cytoskeletal dynamics and cortical neurogenesis through RhoA signaling
Authors: Amar Megha , Pramod Akula Bala , Yu Nam-Kyung , Herrera Victor Munive , Qiu Lily R. , Moran-Losada Patricia , Zhang Pan , Trujillo Cleber A. , Ellegood Jacob , Urresti Jorge , Chau Kevin , Diedrich Jolene , Chen Jiaye , Gutierrez Jessica , Sebat Jonathan , Ramanathan Dhakshin , Lerch Jason P. , Yates John R. , Muotri Alysson R. , Iakoucheva Lilia M. 
Published: February 2020

SummaryE3-ubiquitin ligase Cullin3 (Cul3) is a high confidence risk gene for Autism Spectrum Disorder (ASD) and Developmental Delay (DD). To investigate howCul3mutations impact brain development, we generated haploinsufficientCul3mouse model using CRISPR/Cas9 genome engineering.Cul3mutant mice exhibited social and cognitive deficits and hyperactive behavior. Brain MRI found decreased volume of cortical regions and changes in many other brain regions ofCul3mutant mice starting from early postnatal development. Spatiotemporal transcriptomic and proteomic profiling of the brain implicated neurogenesis and cytoskeletal defects as key drivers ofCul3functional impact. Specifically, dendritic growth, filamentous actin puncta, and spontaneous network activity were reduced inCul3mutant mice. Inhibition of small GTPase RhoA, a molecular substrate of Cul3 ligase, rescued dendrite length and network activity phenotypes. Our study identified neuronal cytoskeleton and Rho signaling as primary targets ofCul3mutation during early brain development.
A Cohort Study: Evaluating Self-Efficacy in Adolescents Attending a Tailored Youth-Informed Breastfeeding Program
Authors: Cantin Christina M. , Peterson Wendy E. , Agarwal Amisha , Hamid Jemila S. , Stortini Bianca , Fleming Nathalie 
Published: February 2020

ABSTRACTAdolescents (≤19 years of age) have lower rates of breastfeeding (BF) compared to older mothers. BF self-efficacy (SE), defined as a mother’s confidence in her ability to breastfeed her infant, has been identified as an important factor influencing BF outcomes. An innovative youth-informed BF program for young women was designed and implemented, which included staff training, a prenatal BF class and BF peer support. The objective of this cohort study was to evaluate the effectiveness of the program in improving young mother’s BF SE.Participants were pregnant adolescents recruited from a large urban non-profit social service outreach centre. The Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF) was administered to participants before and after participating in the BF program. BSES-SF scores were summed to determine a composite score and compared descriptively using mean score. Un-aggregated, item-by-item, comparison of pre-vs post-BF program scores were also compared to examine improvements in SE. A total of 20 adolescent mothers (mean age = 16.6) attended the BF program. An increase in the total BSES-SF score was observed based on descriptively comparing the mean pre vs post intervention.Prenatal education and peer support adapted to the needs of adolescent mothers was associated with increased BSES-SF. These results are promising given that clients attending programs at this agency have low-income, low educational attainment, variable family support, housing instability, and are at-risk for not breastfeeding. Future studies with larger cohort are required to further validate and establish generalizability, as well as to determine the effect on BF duration rates.
Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP)
Authors: Wan Suxin , Yi Qingjie , Fan Shibing , Lv Jinglong , Zhang Xianxiang , Guo Lian , Lang Chunhui , Xiao Qing , Xiao Kaihu , Yi Zhengjun , Qiang Mao , Xiang Jianglin , Zhang Bangshuo , Chen Yongping 
Published: February 2020

AbstractBackgroundTo explore the cellular immunity and cytokines status of NCP patients and to predict the correlation between the cellular immunity levels, cytokines and the severity of patients.Methods123 NCP patients were divided into mild and severe groups. Peripheral blood was collected, lymphocyte subsets and cytokines were detected. Correlation analysis was performed on the lymphocyte subsets and cytokines, and the differences between the indexes of the two groups were analyzed.Results102 mild and 21 severe patients were included. Lymphocyte subsets were reduced in two groups. The proportion of CD8 + T reduction in the mild and severe group was 28.43% and 61.9%, respectively; The proportion of B cell reduction was 25.49% and 28.57%; The proportion of NK cell reduction was 34.31% and 47.62%; The detection value of IL-6 was 0 in 55.88% of the mild group, mild group has a significantly lower proportion of patients with IL-6 higher than normal than severe group; There was no significant linear correlation between the lymphocyte subsets and cytokines, while significant differences were noticed between the two groups in CD4 + T, CD8 + T, IL-6 and IL-10.ConclusionsLow levels of CD4+T and CD8+T are common in severe NCP. IL-6 and IL-10 levels were higher in severe patients. T cell subsets and cytokines can be used as one of the basis for predicting the transition from mild to severe. Large number of samples are still needed to confirm the “warning value” of CD4 + T, CD8 + T IL-6 and IL-10.
Protein-carbohydrate ingestion alters Vps34 cellular localization independent of changes in kinase activity in human skeletal muscle
Authors: Hodson Nathan , Dent Jessica R. , Song Zhe , O’Leary Mary F. , Nicholson Thomas , Jones Simon W. , Murray James T. , Jeromson Stewart , Hamilton D. Lee , Breen Leigh , Philp Andrew 
Published: February 2020

AbstractThe mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) regulates cell size and growth in response to nutrients, however, the mechanisms by which nutrient levels are sensed by mTORC1 in human skeletal muscle are yet to be fully elucidated. The Class III PI3Kinase Vps34 has recently been proposed as a sensor essential for mTORC1 activation following nutrient stimulation. We therefore investigated the effects of increasing nutrient availability through protein-carbohydrate (PRO-CHO) feeding on Vps34 kinase activity and cellular localization in human skeletal muscle. Eight young, healthy males (age – 21 ± 0.5yrs, mean ± SEM) ingested a PRO-CHO beverage containing 20/44/1g PRO/CHO/FAT respectively, with skeletal muscle biopsies obtained at baseline and 1h and 3h post-feeding. PRO-CHO feeding did not alter Vps34 kinase activity, but did stimulate Vps34 translocation toward the cell periphery (PRE (mean±SEM) - 0.273±0.021, 1h - 0.347±0.022, Pearson’s Coefficient (r)) where it co-localized with mTOR (PRE – 0.312±0.018, 1h – 0.348±0.024, Pearson’s Coefficient (r))). These alterations occurred in parallel to an increase in S6K1 kinase activity – 941±164% of PRE at 1h post-feeding). Subsequentin vitroexperiments in C2C12 and human primary myotubes displayed no effect of the Vps34-specific inhibitor SAR405 on mTORC1 signalling responses to elevated nutrient availability. Therefore, in summary, PRO-CHO ingestion does not increase Vps34 activity in human skeletal muscle, whilst pharmacological inhibition of Vps34 does not prevent nutrient stimulation of mTORC1in vitro. However, PRO-CHO ingestion promotes Vps34 translocation to the cell periphery, enabling Vps34 to associate with mTOR. Therefore, our data suggests that interaction between Vps34 and mTOR, rather than changes in Vps34 activityper semay be involved in PRO-CHO activation of mTORC1 in human skeletal muscle.
Ubiquitin ligase component LRS1 and transcription factor CrHy5 act as a light switch for photoprotection inChlamydomonas
Authors: Lämmermann Nina , Wulf Donat , Chang Kwang Suk , Wichmann Julian , Jang Junhwan , Jin EonSeon , Bräutigam Andrea , Wobbe Lutz , Kruse Olaf 
Published: February 2020

ABSTRACTSurvival under excess light conditions requires the light-induced accumulation of protein LHCSR3 and other photoprotection factors, to enable efficient energy-dependent quenching in the green microalgaChlamydomonas reinhardtii. Here, we demonstrate that the high light-tolerant phenotype of mutanthit1is caused by a de-repression of promoters belonging to photoprotection genes, which in turn results from an inactivation of the E3 ubiquitin ligase substrate adaptor LRS1. Transcriptome analyses ofhit1revealed massive alterations of gene expression modulation as a consequence of perturbed LRS1 function, indicating its role as a crown regulator. In conjunction with random forest-based network modeling, these transcriptome analyses predicted that LRS1 controls photoprotection gene expression via an algal HY5 homolog as its prime transcription factor target. CrHY5 binds to T-box elements present in the promoters of these genes and its inactivation in thehit1mutant via CRISPR-Cas9 genome editing, confirmed the regulatory connection between LRS1 and CrHY5, predicted by the network analysis.
Arid1aloss potentiates pancreatic β-cell regeneration through activation of EGF signaling
Authors: Celen Cemre , Chuang Jen-Chieh , Shen Shunli , Otto Jordan E. , Collings Clayton K. , Luo Xin , Li Lin , Wang Yunguan , Wang Zixi , Jia Yuemeng , Sun Xuxu , Nassour Ibrahim , Park Jiyoung , Ghaben Alexandra , Wang Tao , Wang Sam C. , Scherer Philipp E. , Kadoch Cigall , Zhu Hao 
Published: February 2020

SummaryThe dynamic regulation of β-cell abundance is poorly understood. Since chromatin remodeling plays critical roles in liver regeneration, these mechanisms could be generally important for regeneration in other tissues. Here we show that the ARID1A mammalian SWI/SNF complex subunit is a critical regulator of β-cell regeneration.Arid1ais highly expressed in quiescent β-cells but is physiologically suppressed when β-cells proliferate during pregnancy or after pancreas resection. Whole-bodyArid1aknockout mice were protected against streptozotocin induced diabetes. Cell-type and temporally specific genetic dissection showed that β-cell specificArid1adeletion could potentiate β-cell regeneration in multiple contexts. Transcriptomic and epigenomic profiling of mutant islets revealed increased Neuregulin-ERBB-NR4A signaling. Functionally,ERBB3overexpression in β-cells was sufficient to protect against diabetes, and chemical inhibition of ERBB or NR4A was able to block increased regeneration associated withArid1aloss. mSWI/SNF complex activity is a barrier to β-cell regeneration in physiologic and disease states.
Reduced language lateralization in autism and the broader autism phenotype as assessed with robust individual-subjects analyses
Authors: Jouravlev Olessia , Kell Alexander J.E. , Mineroff Zachary , Haskins A.J. , Ayyash Dima , Kanwisher Nancy , Fedorenko Evelina 
Published: February 2020

AbstractOne of the few replicated functional brain differences between individuals with autism spectrum disorders (ASD) and neurotypical (NT) controls is reduced language lateralization. However, most prior reports relied on comparisons of group-level activation maps or functional markers that had not been validated at the individual-subject level, and/or used tasks that do not isolate language processing from other cognitive processes, complicating interpretation. Furthermore, few prior studies have examined functional responses in other functional networks, as needed to determine the selectivity of the effect. Using fMRI, we compared language lateralization between 28 ASD participants and carefully pairwise-matched controls, with the language regions defined individually with a well-validated language localizer. ASD participants showed less lateralized responses due to stronger right hemisphere activations. Further, this effect did not stem from a ubiquitous reduction in lateralization across the brain: ASD participants did not differ from controls in the lateralization of two other large-scale networks—the Theory of Mind network and the Multiple Demand network. Finally, in an exploratory study, we tested whether reduced language lateralization may also be present in NT individuals with high autistic trait load. Indeed, autistic trait load in a large set of NT participants (n=189) was associated with less lateralized language activations. These results suggest that reduced language lateralization is a robust and spatially selective neural marker of autism, present in individuals with ASD, but also in NT individuals with higher genetic liability for ASD, in line with a continuum model of underlying genetic risk.
Vegetative nuclear positioning is required for calcium and ROS signaling in Arabidopsis pollen tubes
Authors: Moser Morgan , Kirkpatrick Andrew , Groves Norman Reid , Meier Iris 
Published: February 2020

AbstractEfficient transport and delivery of sperm cells (SCs) is vital for angiosperm plant fertility. InArabidopsis thaliana, SCs are transported through the growing pollen tube by a connection with the vegetative nucleus (VN). During pollen tube growth, the VN leads the way and maintains a fixed distance from the pollen tube tip, while the SCs lag behind the VN. Upon reception at the ovule, the pollen tube bursts and the SCs are released for fertilization. In pollen tubes of Arabidopsis mutantswit12andwifi, deficient in the outer nuclear membrane component of a plant LINC complex, the SCs precede the VN and the VN falls behind. Subsequently, pollen tubes frequently fail to burst upon reception. In this study, we sought to determine if the pollen tube reception defect observed inwit12andwifiis due to decreased sensitivity to reactive oxygen species (ROS). Here we show thatwit12andwifiare hyposensitive to exogenous H2O2, and that this hyposensitivity is correlated with decreased proximity of the VN to the pollen tube tip. Additionally, we report the first instance of nuclear Ca2+spikes in growing pollen tubes, which are disrupted in thewit12mutant. In thewit12mutant, nuclear Ca2+spikes are reduced in response to exogenous ROS, but these spikes are not correlated with pollen tube burst. This study finds that VN proximity to the pollen tube tip is required for both response to exogenous ROS, as well as internal nuclear Ca2+fluctuations.SummaryMutants deficient in outer nuclear membrane proteins display defects in reactive oxygen species-induced pollen tube burst and nuclear Ca2+signatures that correlate with the position of the vegetative nucleus.
Mechanics regulate human embryonic stem cell self-organization to specify mesoderm
Authors: Muncie Jonathon M. , Ayad Nadia M.E. , Lakins Johnathon N. , Weaver Valerie M. 
Published: February 2020

AbstractEmbryogenesis is directed by morphogens that induce differentiation within a defined tissue geometry. Tissue organization is mediated by cell-cell and cell-extracellular matrix (ECM) adhesions and is modulated by cell tension and tissue-level force. Whether cell tension regulates development by directly influencing morphogen signaling remains unclear. Human embryonic stem cells (hESCs) exhibit an intrinsic capacity for self-organization that motivates their use as a tractable model of early human embryogenesis. We engineered patterned substrates that enhance cell-cell interactions to direct the self-organization of cultured hESCs into “gastrulation-like” nodes. Tissue geometries that generate local nodes of high cell-cell tension and induce these self-organized tissue nodes drive BMP4-dependent gastrulation by enhancing phosphorylation and nuclear translocation of β-catenin to promote Wnt signaling and mesoderm specification. The findings underscore the interplay between tissue organization, cell tension, and morphogen-dependent differentiation, and demonstrate that cell- and tissue-level forces directly regulate cell fate specification in early human development.Graphical AbstractHighlightsSubstrates that enhance cell-cell adhesion promote hESC self-organizationTissue nodes exhibiting high tension are predisposed to gastrulation inductionColony geometry dictates the localization of tension nodes to specify mesodermTension activates β-catenin and stimulates Wnt signaling to induce mesodermIn BriefEngineered substrates that promote cell-cell adhesion and reconstitute epiblast tissue organization facilitate “gastrulation-like” morphogenesis in cultured hESCs. Tissue geometries that foster localized regions of high cell-cell tension potentiate BMP4-dependent mesoderm specification by enhancing phosphorylation and nuclear translocation of β-catenin to promote Wnt signaling.
Evidence that ion conduction in 5-HT3Areceptors proceeds through lateral portals in the cytosol
Authors: Stuebler Antonia G. , Jansen Michaela 
Published: February 2020

AbstractThe intracellular domain of the serotonin type 3A receptor, a pentameric ligand-gated ion channel, is crucial for regulating conductance. However, the specific ion conduction pathway through this domain is less clear. The intracellular domain starts with a short loop after the third transmembrane segment, followed by a short α-helical segment, a large unstructured loop, and finally the membrane-associated MA-helix that continues into the last transmembrane segment. The MA-helices from all five subunits form the extension of the transmembrane ion channel and shape what has been described as a “closed vestibule”, with their lateral portals obstructed by loops and their cytosolic ends forming a tight hydrophobic constriction. The question remains whether the lateral portals or cytosolic constriction conduct ions upon channel opening. In the present study, we used disulfide bond formation between pairs of engineered cysteines to probe the proximity and mobility of segments of the MA-helices most distal to the membrane bilayer. Our results indicate that the proximity and orientation for cysteine pairs at I409C/R410C, in close proximity to the lateral windows, and L402C/L403C, at the cytosolic ends of the MA-helices, are conducive for disulfide bond formation. While conformational changes associated with gating promote crosslinking for I409C/R410C, which in turn decreases channel currents, crosslinking of L402C/L403C is functionally silent in macroscopic currents. These results support the hypothesis that concerted conformational changes open the lateral portals for ion conduction, rendering ion conduction through the vertical portal unlikely.SignificanceThe intracellular domain (ICD) of pentameric ligand-gated ion channels (pLGICs) is the most diverse domain within receptors of the Cys-loop superfamily. Despite being the least understood domain of pLGICs, its impact on ion-channel function and contribution to the cytosolic exit pathway of the channel have been investigated. X-ray and cryo-EM structures have captured the structured segments of the ICD of 5-HT3Areceptors in different conformational states with lower resolution of the ICD as compared to the other domains. Here, we provide experimentally derived evidence for the importance of the differential mobility of the cytosolic segment of the MA-helices, which supports the existence of lateral portals as opposed to a vertical pathway for 5-HT3Areceptors.