A Novel microRNA and transcription factor mediated regulatory network in schizophrenia

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is a complex brain disorder with molecular mechanisms that have yet to be elucidated. Previous studies have suggested that changes in gene expression may play an important role in the etiology of schizophrenia, and that microRNAs (miRNAs) and transcription factors (TFs) are primary regulators of this gene expression. So far, several miRNA-TF mediated regulatory modules have been verified. We hypothesized that miRNAs and TFs might play combinatory regulatory roles for schizophrenia genes and, thus, explored miRNA-TF regulatory networks in schizophrenia.</p> <p>Results</p> <p>We identified 32 feed-forward loops (FFLs) among our compiled schizophrenia-related miRNAs, TFs and genes. Our evaluation revealed that these observed FFLs were significantly enriched in schizophrenia genes. By converging the FFLs and mutual feedback loops, we constructed a novel miRNA-TF regulatory network for schizophrenia. Our analysis revealed EGR3 and hsa-miR-195 were core regulators in this regulatory network. We next proposed a model highlighting EGR3 and miRNAs involved in signaling pathways and regulatory networks in the nervous system. Finally, we suggested several single nucleotide polymorphisms (SNPs) located on miRNAs, their target sites, and TFBSs, which may have an effect in schizophrenia gene regulation.</p> <p>Conclusions</p> <p>This study provides many insights on the regulatory mechanisms of genes involved in schizophrenia. It represents the first investigation of a miRNA-TF regulatory network for a complex disease, as demonstrated in schizophrenia.</p

OPM3® Portugal project: analysis of preliminary results

Project Management (PM) has emerged as a crucial factor that determines the success of an organization. In this sense, there is a growing concern for organizations to assess their PM maturity. This paper presents the PM maturity results for 19 organizations, using Organizational Project Management Maturity Model (OPM3®) emerging from OPM3® Portugal Project research, that is presently in progress. All aspects of OPM3® Portugal Project are explained in detail, and a brief descriptive analysis of the 19 organizations assessed is presented. The preliminary results were obtained using two scoring methods, and are presented in tables organized by PM processes, Portfolio Management processes and Organizational Enablers areas. No other similar studies were found, thus it was not possible to compare the preliminary Portuguese results with other results

Schizophrenia Gene Networks and Pathways and Their Applications for Novel Candidate Gene Selection

Background Schizophrenia (SZ) is a heritable, complex mental disorder. We have seen limited success in finding causal genes for schizophrenia from numerous conventional studies. Protein interaction network and pathway-based analysis may provide us an alternative and effective approach to investigating the molecular mechanisms of schizophrenia. Methodology/Principal Findings We selected a list of schizophrenia candidate genes (SZGenes) using a multi-dimensional evidence-based approach. The global network properties of proteins encoded by these SZGenes were explored in the context of the human protein interactome while local network properties were investigated by comparing SZ-specific and cancer-specific networks that were extracted from the human interactome. Relative to cancer genes, we observed that SZGenes tend to have an intermediate degree and an intermediate efficiency on a perturbation spreading throughout the human interactome. This suggested that schizophrenia might have different pathological mechanisms from cancer even though both are complex diseases. We conducted pathway analysis using Ingenuity System and constructed the first schizophrenia molecular network (SMN) based on protein interaction networks, pathways and literature survey. We identified 24 pathways overrepresented in SZGenes and examined their interactions and crosstalk. We observed that these pathways were related to neurodevelopment, immune system, and retinoic X receptor (RXR). Our examination of SMN revealed that schizophrenia is a dynamic process caused by dysregulation of the multiple pathways. Finally, we applied the network/pathway approach to identify novel candidate genes, some of which could be verified by experiments. Conclusions/Significance This study provides the first comprehensive review of the network and pathway characteristics of schizophrenia candidate genes. Our preliminary results suggest that this systems biology approach might prove promising for selection of candidate genes for complex diseases. Our findings have important implications for the molecular mechanisms for schizophrenia and, potentially, other psychiatric disorders

Diagenetic–Porosity Evolution and Reservoir Evaluation in Multiprovenance Tight Sandstones: Insight from the Lower Shihezi Formation in Hangjinqi Area, Northern Ordos Basin

AbstractThe reservoir property of tight sandstones is closely related to the provenance and diagenesis, and multiprovenance system and complex diagenesis are developed in Hangjinqi area. However, the relationship between provenance, diagenesis, and physical characteristics of tight reservoirs in Hangjinqi area has not yet been reported. The Middle Permian Lower Shihezi Formation is one of the most important tight gas sandstone reservoirs in the Hangjinqi area of Ordos Basin. This research compared the diagenesis-porosity quantitative evolution mechanisms of Lower Shihezi Formation sandstones from various provenances in the Hangjinqi area using thin-section descriptions, cathodoluminescence imaging, X-ray diffraction (XRD), scanning electron microscopy (SEM), and homogenization temperature of fluid inclusions, along with general physical data and high-pressure mercury intrusion (HPMI) data. The sandstones mainly comprise quartzarenite, sublitharenite, and litharenite with low porosity and low permeability and display obvious zonation in the content of detrital components as a result of multiprovenance. Pore space of those sandstone mainly consists of primary pores, secondary pores, and microfractures, but their proportion varies in different provenances. According to HPMI, the order of the pore-throat radius from largest to smallest is central provenance, eastern provenance, and western provenance, which is consistent with the change tend of porosity (middle part&gt;northern part&gt;western part) in Hangjinqi region. The diagenetic evolution path of those sandstones is comparable, with compaction, cementation, dissolution, and fracture development. The central provenance has the best reservoir quality, followed by the eastern provenance and the western provenance, and this variation due to the diverse diagenesis (diagenetic stage and intensity) of different provenances. These findings reveal that the variations in detrital composition and structure caused by different provenances are the material basis of reservoir differentiation, and the main rationale for reservoir differentiation is varying degrees of diagenesis during burial process

A Frameshift Variant in the CHST9 Gene Identified by Family-Based Whole Genome Sequencing Is Associated with Schizophrenia in Chinese Population

Recent studies imply that rare variants contribute to the risk of schizophrenia, however, the exact variants or genes responsible for this condition are largely unknown. In this study, we conducted whole genome sequencing (WGS) of 20 Chinese families. Each family consisted of at least two affected siblings diagnosed with schizophrenia and at least one unaffected sibling. We examined functional variants that were found in affected sibling(s) but not in unaffected sibling(s) within a family. Matching this criterion, a frameshift heterozygous deletion of CA (–/CA) at chromosome 18:24722722, also referred to as rs752084147, in the Carbohydrate Sulfotransferase 9 (CHST9) gene, was detected in two families. This deletion was confirmed by PCR-based Sanger sequencing. With the observed frequency of 0.00076 in Han Chinese population, we performed both case-control and family-based analyses to evaluate its association with schizophrenia. In the case-control analyses, Chi-square test P-value was 6.80e-12 and the P-value was 0.0008 after one million simulations. In family-based segregation analyses, segregation P-value was 7.72e-7 and simulated P-value was 5.70e-6. For both the case-control and family-based analyses, the CA deletion was significantly associated with schizophrenia in the Chinese population. Further investigation of this gene is warranted in the development of schizophrenia by utilizing larger and more ethnically diverse samples

CNx-modified Fe3O4 as Pt nanoparticle support for the oxygen reduction reaction

A novel electrocatalyst support material, nitrogendoped carbon (CNx)-modified Fe3O4 (Fe3O4-CNx), was synthesized through carbonizing a polypyrrole-Fe3O4 hybridized precursor. Subsequently, Fe3O4-CNx-supported Pt (Pt/Fe3O4-CNx) nanocomposites were prepared by reducing Pt precursor in ethylene glycol solution and evaluated for the oxygen reduction reaction (ORR). The Pt/Fe3O4-CNx catalysts were characterized by X-ray diffraction, Raman spectra, X-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy. The electrocatalytic activity and stability of the as-prepared electrocatalysts toward ORR were studied by cyclic voltammetry and steady-state polarization measurements. The results showed that Pt/ Fe3O4-CNx catalysts exhibited superior catalytic performance for ORR to the conventional Pt/C and Pt/C-CNx catalysts.Web of Scienc

Electrochemical mechanical micromachining based on confined etchant layer technique

National Science Foundation of China [91023006, 91023047, 91023043, 21061120456, 21021002]; Natural Science Foundation of Fujian Province of China [2012J06004]; Fundamental Research Funds for the Central Universities [2010121022]; Scientific Research Foundation for the Returned Overseas Chinese Scholars (State Education Ministry)The confined etchant layer technique (CELT) has been proved an effective electrochemical microfabrication method since its first publication at Faraday Discussions in 1992. Recently, we have developed CELT as an electrochemical mechanical micromachining (ECMM) method by replacing the cutting tool used in conventional mechanical machining with an electrode, which can perform lathing, planing and polishing. Through the coupling between the electrochemically induced chemical etching processes and mechanical motion, ECMM can also obtain a regular surface in one step. Taking advantage of CELT, machining tolerance and surface roughness can reach micro-or nano-meter scale

Retraction Note: Identification of de Novo Mutations in Prenatal Neurodevelopment-Associated Genes in Schizophrenia in Two Han Chinese Patient-Sibling Family-Based Cohorts (Translational Psychiatry, (2020), 10, 1, (307), 10.1038/s41398-020-00987-Z)

© 2020, The Author(s). This article1 has been retracted at the request of Authors Xingwang Li and Lin He. After publication, it was realized that approval to use data from the NSFC-NIH Sino-US cooperation project (Project No. 81361120389) was not obtained from the data owners. Authors Dongmei Cao, Xiangning Chen, Lin He, Kenneth Kendler, Xingwang Li, Travis Mize, Chunling Wan and Jain-Shing Wu agree to this retraction. Authors Shan Jiang, Jingchun Chen and Zongming Zhao do not agree to this retraction. Authors Guang He, Peilin Jia, Xiaoqian Jiang, Yimei Lu, Ming Tsuang, Yin-Ying Wang and Daizhan Zhou did not respond to correspondence from the Publisher about this retraction

Genetic Relationship between Schizophrenia and Nicotine Dependence

It is well known that most schizophrenia patients smoke cigarettes. There are different hypotheses postulating the underlying mechanisms of this comorbidity. We used summary statistics from large meta-analyses of plasma cotinine concentration (COT), Fagerström test for nicotine dependence (FTND) and schizophrenia to examine the genetic relationship between these traits. We found that schizophrenia risk scores calculated at P-value thresholds of 5 × 10−3 and larger predicted FTND and cigarettes smoked per day (CPD), suggesting that genes most significantly associated with schizophrenia were not associated with FTND/CPD, consistent with the self-medication hypothesis. The COT risk scores predicted schizophrenia diagnosis at P-values of 5 × 10−3 and smaller, implying that genes most significantly associated with COT were associated with schizophrenia. These results implicated that schizophrenia and FTND/CPD/COT shared some genetic liability. Based on this shared liability, we identified multiple long non-coding RNAs and RNA binding protein genes (DA376252, BX089737, LOC101927273, LINC01029, LOC101928622, HY157071, DA902558, RBFOX1 and TINCR), protein modification genes (MANBA, UBE2D3, and RANGAP1) and energy production genes (XYLB, MTRF1 and ENOX1) that were associated with both conditions. Further analyses revealed that these shared genes were enriched in calcium signaling, long-term potentiation and neuroactive ligand-receptor interaction pathways that played a critical role in cognitive functions and neuronal plasticity.</p

Genetic Relationship between Schizophrenia and Nicotine Dependence

It is well known that most schizophrenia patients smoke cigarettes. There are different hypotheses postulating the underlying mechanisms of this comorbidity. We used summary statistics from large meta-analyses of plasma cotinine concentration (COT), Fagerstrom test for nicotine dependence (FTND) and schizophrenia to examine the genetic relationship between these traits. We found that schizophrenia risk scores calculated at P-value thresholds of 5 x 10(-3) and larger predicted FTND and cigarettes smoked per day (CPD), suggesting that genes most significantly associated with schizophrenia were not associated with FTND/CPD, consistent with the self-medication hypothesis. The COT risk scores predicted schizophrenia diagnosis at P-values of 5 x 10(-3) and smaller, implying that genes most significantly associated with COT were associated with schizophrenia. These results implicated that schizophrenia and FTND/CPD/COT shared some genetic liability. Based on this shared liability, we identified multiple long non-coding RNAs and RNA binding protein genes (DA376252, BX089737, LOC101927273, LINC01029, LOC101928622, HY157071, DA902558, RBFOX1 and TINCR), protein modification genes (MANBA, UBE2D3, and RANGAP1) and energy production genes (XYLB, MTRF1 and ENOX1) that were associated with both conditions. Further analyses revealed that these shared genes were enriched in calcium signaling, long-term potentiation and neuroactive ligand-receptor interaction pathways that played a critical role in cognitive functions and neuronal plasticity.Peer reviewe