bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain connectivity alterations in early psychosis: from clinical to neuroimaging staging
Authors: Griffa Alessandra , Baumann Philipp S. , Klauser Paul , Mullier Emeline , Cleusix Martine , Jenni Raoul , van den Heuvel Martijn P. , Do Kim Q. , Conus Philippe , Hagmann Patric 
Published: February 2019

AbstractEarly in the course of psychosis, alterations in brain connectivity accompany the emergence of psychiatric symptoms and cognitive impairments, including processing speed. The clinical-staging model is a refined form of diagnosis that places the patient along a continuum of illness conditions, which allows stage-specific interventions with the potential of improving patient care and outcome. This cross-sectional study investigates brain connectivity features that characterize the clinical stages following a first psychotic episode. Structural brain networks were derived from diffusion-weighted MRI for 71 early-psychosis patients and 76 healthy controls. Patients were classified into stage II (first-episode), IIIa (incomplete remission), IIIb (one relapse), and IIIc (two or more relapses), according to the course of the illness until the time of scanning. Brain connectivity measures and diffusion parameters (fractional anisotropy, apparent diffusion coefficient) were investigated using general linear models and sparse linear discriminant analysis (sLDA), studying distinct subgroups of patients who were at specific stages of early psychosis. We found that brain connectivity impairments were more severe in clinical stages following the first-psychosis episode (stages IIIa, IIIb, IIIc) than in first-episode psychosis (stage II) patients. These alterations were spatially diffuse but converged on a set of vulnerable regions, whose inter-connectivity selectively correlated with processing speed in patients and controls. The sLDA suggested that relapsing-remitting (stages IIIb, IIIc) and non-remitting (stage IIIa) patients are characterized by distinct dysconnectivity profiles. Our results indicate that neuroimaging markers of brain dysconnectivity in early psychosis may reflect the heterogeneity of the illness and provide a connectomics signature of the clinical-staging model.
Genetic loci for alcohol-related life events and substance-induced affective symptoms: indexing the “dark side” of addiction
Authors: Peng Qian , Bizon Chris , Gizer Ian R. , Wilhelmsen Kirk C. , Ehlers Cindy L. 
Published: February 2019

AbstractA limited number of genetic variants have been identified in traditional GWAS as risk or protective factors for alcohol use disorders (AUD) and related phenotypes. We herein report whole-genome association and rare-variant analyses on AUD traits in American Indians (AI) and European Americans (EA). We evaluated 742 AIs and 1711 EAs using low-coverage whole-genome sequencing. Phenotypes included: (1) a metric based on the occurrence of 36 alcohol-related life events that reflect AUD severity; (2) two alcohol-induced affective symptoms that accompany severe AUDs. We identified two new loci for alcohol-related life events with converging evidence from both cohorts: rare variants of K2Pchannel geneKCNK2, and rare missense and splice-site variants in pro-inflammatory mediator genePDE4C. ANAF1-FSTL5intergenic variant and anFSTL5variant were respectively associated with alcohol-related life events in AI and EA.PRKG2of serine/threonine protein kinase family, and rare variants in interleukin subunit geneEBI3(IL-27B) were uniquely associated with alcohol-induced affective symptoms in AI. LncRNALINC02347on 12q24.32 was uniquely associated with alcohol-induced depression in EA. The top GWAS findings were primarily rare/low-frequency variants in AI, and common variants in EA. Adrenal gland was the most enriched in tissue-specific gene expression analysis for alcohol-related life events, and nucleus accumbens was the most enriched for alcohol-induced affective states in AI. Prefrontal cortex was the most enriched in EA for both traits. These studies suggest that whole-genome sequencing can identify novel, especially uncommon, variants associated with severe AUD phenotypes although the findings may be population specific.
Affective modulation of the associative-limbic subthalamic nucleus: deep brain stimulation in obsessive–compulsive disorder
Authors: Polosan Mircea , Droux Fabien , Kibleur Astrid , Chabardes Stephan , Bougerol Thierry , David Olivier , Krack Paul , Voon Valerie 
Published: February 2019

AbstractAffective states underlie daily decision-making and pathological behaviours relevant to obsessive–compulsive disorders (OCD), mood disorders and addictions. Deep brain stimulation targeting the motor and associative-limbic subthalamic nucleus (STN) has been shown to be effective for Parkinson’s disease (PD) and OCD, respectively. Cognitive and electrophysiological studies in PD showed responses of the motor STN to emotional stimuli, impairments in recognition of negative affective states and modulation of the intensity of subjective emotion. Here we studied whether the stimulation of the associative-limbic STN in OCD influences the subjective emotion to low-intensity positive and negative images and how this relates to clinical symptoms. We assessed 10 OCD patients with on and off STN DBS in a double-blind randomized manner by recording ratings of valence and arousal to low- and high-intensity positive and negative emotional images. STN stimulation increased positive ratings and decreased negative ratings to low-intensity positive and negative stimuli, respectively, relative to off stimulation. We also show that the change in severity of obsessive–compulsive symptoms pre- versus post-operatively interacts with both DBS and valence ratings. We show that stimulation of the associative-limbic STN might influence the negative cognitive bias in OCD and decreasing the negative appraisal of emotional stimuli with a possible relationship with clinical outcomes. That the effect is specific to low intensity might suggest a role of uncertainty or conflict related to competing interpretations of image intensity. These findings may have implications for the therapeutic efficacy of DBS.
Dynamic expression of genes associated with schizophrenia and bipolar disorder across development
Authors: Clifton Nicholas E. , Hannon Eilís , Harwood Janet C. , Di Florio Arianna , Thomas Kerrie L. , Holmans Peter A. , Walters James T. R. , O’Donovan Michael C. , Owen Michael J. , Pocklington Andrew J. , Hall Jeremy 
Published: February 2019

AbstractCommon genetic variation contributes a substantial proportion of risk for both schizophrenia and bipolar disorder. Furthermore, there is evidence of significant, but not complete, overlap in genetic risk between the two disorders. It has been hypothesised that genetic variants conferring risk for these disorders do so by influencing brain development, leading to the later emergence of symptoms. The comparative profile of risk gene expression for schizophrenia and bipolar disorder across development over different brain regions however remains unclear. Using genotypes derived from genome-wide associations studies of the largest available cohorts of patients and control subjects, we investigated whether genes enriched for schizophrenia and bipolar disorder association show a bias for expression across any of 13 developmental stages in prefrontal cortical and subcortical brain regions. We show that genetic association with schizophrenia is positively correlated with expression in the prefrontal cortex during early midfetal development and early infancy, and negatively correlated with expression during late childhood, which stabilises in adolescence. In contrast, risk-associated genes for bipolar disorder did not exhibit a bias towards expression at any prenatal stage, although the pattern of postnatal expression was similar to that of schizophrenia. These results highlight the dynamic expression of genes harbouring risk for schizophrenia and bipolar disorder across prefrontal cortex development and support the hypothesis that prenatal neurodevelopmental events are more strongly associated with schizophrenia than bipolar disorder.
Longitudinal investigation of DNA methylation changes preceding adolescent psychotic experiences
Authors: Roberts Susanna , Suderman Matthew , Zammit Stanley , Watkins Sarah H. , Hannon Eilis , Mill Jonathan , Relton Caroline , Arseneault Louise , Wong Chloe C. Y. , Fisher Helen L. 
Published: February 2019

AbstractChildhood psychotic experiences (PEs), such as seeing or hearing things that others do not, or extreme paranoia, are relatively common with around 1 in 20 children reporting them at age 12. Childhood PEs are often distressing and can be predictive of schizophrenia, other psychiatric disorders, and suicide attempts in adulthood, particularly if they persist during adolescence. Previous research has demonstrated that methylomic signatures in blood could be potential biomarkers of psychotic phenomena. This study explores the association between DNA methylation (DNAm) and the emergence, persistence, and remission of PEs in childhood and adolescence. DNAm profiles were obtained from the ALSPAC cohort at birth, age 7, and age 15/17 (n = 901). PEs were assessed through interviews with participants at ages 12 and 18. We identified PE-associated probes (p < 5 × 10−5) and regions (corrected p < 0.05) at ages 12 and 18. Several of the differentially methylated probes were also associated with the continuity of PEs across adolescence. One probe (cg16459265), detected consistently at multiple timepoints in the study sample, was replicated in an independent sample of twins (n = 1658). Six regions, including those spanning the HLA-DBP2 and GDF7 genes, were consistently differentially methylated at ages 7 and 15–17. Findings from this large, population-based study suggest that DNAm at multiple stages of development may be associated with PEs in late childhood and adolescence, though further replication is required. Research uncovering biomarkers associated with pre-clinical PEs is important as it has the potential to facilitate early identification of individuals at increased risk who could benefit from preventive interventions.
Cul4 E3 ubiquitin ligase regulates ovarian cancer drug resistance by targeting the antiapoptotic protein BIRC3
Authors: Hu Xiaoyan , Meng Yang , Xu Lian , Qiu Lei , Wei Mingtian , Su Dan , Qi Xu , Wang Ziqiang , Yang Shengyong , Liu Cong , Han Junhong 
Published: February 2019

AbstractCRL4, a well-defined E3 ligase, has been reported to be upregulated and is proposed to be a potential drug target in ovarian cancers. However, the biological functions of CRL4 and the underlying mechanism regulating cancer chemoresistance are still largely elusive. Here, we show that CRL4 is considerably increased in cisplatin-resistant ovarian cancer cells, and CRL4 knockdown with shRNAs is able to reverse cisplatin-resistance of ovarian cancer cells. Moreover, CRL4 knockdown markedly inhibits the expression of BIRC3, one of the inhibitors of apoptosis proteins (IAPs). Besides, lower expression level of BIRC3 is associated with better prognosis of ovarian cancer patients, and BIRC3 knockdown in ovarian cancer cells can recover their sensitivity to cisplatin. More importantly, we demonstrate that CRL4 regulates BIRC3 expression by mediating the STAT3, but not the PI3K pathway. Therefore, our results identified CRL4 as an important factor in ovarian cancer chemoresistance, suggesting that CRL4 and BIRC3 may serve as novel therapeutic targets for relapsed patients after treatment with cisplatin and its derivative to overcome the bottle neck of ovarian cancer chemoresistance.
miR-29c-3p regulates DNMT3B and LATS1 methylation to inhibit tumor progression in hepatocellular carcinoma
Authors: Wu Hao , Zhang Wei , Wu Zhenru , Liu Yan , Shi Yujun , Gong Jianping , Shen Wei , Liu Changan 
Published: February 2019

AbstractAccumulating evidence suggests that microRNAs and DNA methylation can cause tumor suppressor gene inactivation and promote tumor malignancy. However, the functional mechanisms of miR-29c-3p and DNA methylation in hepatocellular carcinoma (HCC) are unclear. Here, we reported that miR-29c-3p expression was significantly downregulated in HCC tissues and cell lines. Low miR-29c-3p expression correlated with tumor size, multiplicity pathologic features, and shorter overall survival. Overexpression of miR-29c-3p significantly inhibited HCC cell proliferation, apoptosis, migration, and tumor growth in vivo. Moreover, DNA methyltransferases 3B (DNMT3B) was upregulated in HCC tissues, and was negatively correlated with miR-29c-3p expression. Luciferase reporter and western blotting assays revealed that DNMT3B is a target gene directly regulated by miR-29c-3p. Furthermore, miR-29c-3p regulates the methylation of large tumor suppressor gene 1 (LATS1) by DNMT3B, and abnormal methylation of LATS1 inactivates Hippo signaling pathway. We subsequently identified that high DNMT3B expression and low LATS1 expression were frequently identified in HCC tissues and were associated with poor prognosis. In conclusion, our results indicate that miR-29c-3p acts as a tumor suppressor in HCC by targeting DNMT3B and the LATS1-associated Hippo signaling pathway, which might represent a novel potential therapeutic target for HCC.
CYTL1 regulates bone homeostasis in mice by modulating osteogenesis of mesenchymal stem cells and osteoclastogenesis of bone marrow-derived macrophages
Authors: Shin Youngnim , Won Yoonkyung , Yang Jeong-In , Chun Jang-Soo 
Published: February 2019

AbstractWe previously showed that mice with knockout of Cytl1, a functionally uncharacterized cytokine candidate, exhibit normal endochondral ossification and long-bone development. Here, we investigated the potential functions of CYTL1 in bone homeostasis. We found that Cytl1−/− mice exhibited higher bone mass than wild-type littermates and resisted ovariectomy-induced bone resorption. This led us to investigate the functions of CYTL1 in the osteogenesis and osteoclastogenesis of bone marrow-derived stem cells. CYTL1 was down-regulated during the osteogenesis of human mesenchymal stem cells (hMSCs). The osteogenesis of hMSCs was inhibited by overexpression or exogenous treatment of CYTL1, but enhanced by CYTL1 knockdown. CYTL1 decreased osteogenesis by inhibiting RUNX2 and promoted proliferation among undifferentiated hMSCs, but stimulated apoptosis among osteogenically differentiating cells. Finally, Cytl1−/− mice exhibited inhibition of osteoclast activity and the osteoclastogenesis of bone marrow-derived macrophages. Our results collectively suggest that CYTL1 negatively regulates the osteogenesis of MSCs and positively regulates osteoclastogenesis to modulate bone mass in mice.
Reconstructing the quantum critical fan of strongly correlated systems using quantum correlations
Authors: Frérot Irénée , Roscilde Tommaso 
Published: February 2019

AbstractAlbeit occurring at zero temperature, quantum critical phenomena have a huge impact on the finite-temperature phase diagram of strongly correlated systems, giving experimental access to their observation. Indeed, the existence of a gapless, zero-temperature quantum critical point induces the existence of an extended region in parameter space—the quantum critical fan (QCF)—characterized by power-law temperature dependences of all observables. Identifying experimentally the QCF and its crossovers to other regimes (renormalized classical, quantum disordered) remains nonetheless challenging. Focusing on paradigmatic models of quantum phase transitions, here we show that quantum correlations—captured by the quantum variance of the order parameter—exhibit the temperature scaling associated with the QCF over a parameter region much broader than that revealed by ordinary correlations. The link existing between the quantum variance and the dynamical susceptibility paves the way to an experimental reconstruction of the QCF using spectroscopic techniques.
Label-free Quantitative Analysis of Protein Expression Alterations in miR-26a-Knockout HeLa Cells using SWATH-MS Technology
Authors: Shen Hexiao , Li Li , Teng Zhaowei , Meng Tianqing , Kong Xiangbin , Hu Yan , Zhu Yun , Ma Lixin 
Published: February 2019

AbstractMicroRNAs (miRNAs) bind to the 3ʹ-untranslated region of target mRNAs in a sequence-specific manner and subsequently repress gene translation. Human miR-26a has been studied extensively, but the target transcripts are far from complete. We first employed the CRISPR-Cas9 system to generate an miR-26a-knockout line in human cervical cancer HeLa cells. The miR26a-knockout line showed increased cell growth and altered proliferation. Proteomics technology of sequential window acquisition of all theoretical mass spectra (SWATH-MS) was utilized to compare the protein abundance between the wild-type and the knockout lines, with an attempt to identify transcripts whose translation was influenced by miR-26a. Functional classification of the proteins with significant changes revealed their function in stress response, proliferation, localization, development, signaling, etc. Several proteins in the cell cycle/proliferation signaling pathway were chosen to be validated by western blot and parallel reaction monitoring (PRM). The satisfactory consistency among the three approaches indicated the reliability of the SWATH-MS quantification. Among the computationally predicted targets, a subset of the targets was directly regulated by miR-26a, as demonstrated by luciferase assays and Western blotting. This study creates an inventory of miR-26a-targeted transcripts in HeLa cells and provides fundamental knowledge to further explore the functions of miR-26a in human cancer.
Quantum-like decreased embryogenesis time with increased cold exposure time
Authors: Vasanthan Tarushika , Nederveen Joshua P. , Stone Jonathon 
Published: February 2019

AbstractThree theoretical models have been proposed to explain lifespan extension resulting from exposure to extreme conditions in microscopic animals: individuals become completely dormant and stop aging, continue to age or age but at a diminished rate. Here we show that the earliest life history stages, embryonic cell divisions, in the tardigrade species Hypsibius dujardini are retarded when eggs are reared at 0 °C. Compared to control specimens reared at 22 °C, juveniles that hatched from eggs exposed to 0 °C for 4 days and returned to 22 °C experienced a three-day lag, indicating that their biological age was less than their chronological age. As cold exposure duration increased (days = 10, 20, 40), incubation period at 22 °C decreased incrementally (days = 3, 2, 1), suggesting that tardigrades involve a threshold-determined, quantum-like, energetic-based system for controlling embryogenesis.
Biofilm Formation of Staphylococcus aureus under Food Heat Processing Conditions: First Report on CML Production within Biofilm
Authors: Miao Jian , Lin Shiqi , Soteyome Thanapop , Peters Brian M. , Li Yanmei , Chen Huishan , Su Jianyu , Li Lin , Li Bing , Xu Zhenbo , Shirtliff Mark E. , harro Janette M. 
Published: February 2019

AbstractThis study aimed to evaluate the Staphylococcus aureus biofilm formation and Nε-carboxymethyl-lysine generation ability under food heat processing conditions including pH (5.0–9.0), temperature (25 °C, 31 °C, 37 °C, 42 °C and 65 °C), NaCl concentration (10%, 15% and 20%, w/v) and glucose concentration (0.5%, 1%, 2%, 3%, 5%, 10%, w/v). S. aureus biofilm genetic character was obtained by PCR detecting atl, ica operon, sasG and agr. Biofilm biomass and metabolic activity were quantified with crystal violet and methyl thiazolyl tetrazolium staining methods. S. aureus biofilm was sensitive to food heat processing conditions with 37 °C, pH 7.0, 2% glucose concentration (w/v) and 10% NaCl concentration (w/v) were favorable conditions. Besides, free and bound Nε-carboxymethyl-lysine level in weak, moderate and strong biofilm were detected by optimized high performance liquid chromatography tandem mass spectrometry. Nε-carboxymethyl-lysine level in S. aureus biofilm possessed a significant gap between strong, moderate and weak biofilm strains. This investigation revealed the biological and chemical hazard of Staphylococcus aureus biofilm to food processing environment.
Structural and biochemical insight into mode of action and subsite specificity of a chitosan degrading enzyme from Bacillus spec. MN
Authors: Singh Ratna , Weikert Tobias , Basa Sven , Moerschbacher Bruno M. 
Published: February 2019

AbstractChitosans, partially de-N-acetylated derivatives of chitin, are multifunctional biopolymers. In nature, biological activities of partially acetylated chitosan polymers are mediated in part by their oligomeric breakdown products, which are generated in situ by the action of chitosanolytic enzymes. Understanding chitosanolytic enzymes, therefore, can lead to the production of chitosan oligomers with fully defined structures that may confer specific bioactivities. To address whether defined oligomer products can be produced via chitosanolytic enzymes, we here characterized a GH8 family chitosanase from Bacillus spec. MN, determining its mode of action and product profiles. We found that the enzyme has higher activity towards polymers with lower degree of acetylation. Oligomeric products were dominated by GlcN3, GlcN3GlcNAc1, and GlcN4GlcNAc1. The product distribution from oligomers were GlcN3 > GlcN2. Modeling and simulations show that the binding site comprises subsites ranging from (−3) to (+3), and a putative (+4) subsite, with defined preferences for GlcN or GlcNAc at each subsite. Flexible loops at the binding site facilitate enzyme-substrate interactions and form a cleft at the active site which can open and close. The detailed insight gained here will help to engineer enzyme variants to produce tailored chitosan oligomers with defined structures that can then be used to probe their specific biological activities.
Diagnostic Value of Circulating microRNAs for In-Stent Restenosis in Patients with Lower Extremity Arterial Occlusive Disease
Authors: Yuan Liangxi , Dong Jian , Zhu Guanglang , Bao Junmin , Lu Qingsheng , Zhou Jian , Jing Zaiping 
Published: February 2019

AbstractIn-stent restenosis (ISR) is still a major cause of failure of endovascular stenting treatment in patients with lower extremity arterial occlusive disease (LEAOD). Sensitive and reliable biomarkers for early diagnosis to predict ISR should be considered. This study was conducted to explore the diagnostic value of microRNA in predicting ISR in patients with LEAOD after endovascular stenting treatment. From March 2014 to July 2016, 208 patients (170 males and 38 females) with LEAOD undergoing interventional treatment were enrolled in this research. Patients were divided into the restenosis and non-restenosis groups according to routine postoperative angiography. Circulating microRNAs expression were detected in 208 participants, including 78 ISR patients, 68 non-ISR patients and 62 healthy volunteers. We selected 6 microRNAs from microarray screening as candidates for further testing via qRT-PCR. A receiver operating characteristic (ROC) curve was generated to assess the diagnostic value of circulating microRNAs in predicting ISR for LEAOD patients. The results showed that circulating microRNA-320a and microRNA-572 in patients with ISR (n = 78) had significantly higher expression levels than it from non-ISR and healthy volunteers. By receiver operating characteristic curve analysis, the sensitivity was 82.1% and the specificity was 63.8% for microRNA-320a; the sensitivity was 69.2% and the specificity was 68.9% for microRNA-572, and the AUC was 0.766 and 0.690 for detection of ISR, respectively. Furthermore, 78 patients with ISR had significantly higher circulating expression levels of microRNA-3937 and microRNA-642a-3p and lower circulating expression levels of microRNA-4669 and microRNA-3138 compared with 68 non-ISR patients and 62 healthy volunteers, but they have no significant difference. We found that differential circulating microRNA expression in patients after stenting with ISR, and the data indicate that circulating microRNA-320a and microRNA-572 have promising value in diagnosing ISR in patients with LEAOD.