Spinocerebellar ataxia type 35 (SCA35)-associated transglutaminase 6 mutants sensitize cells to apoptosis.

Spinocerebellar ataxia type 35 (SCA35) is an autosomal dominant neurodegenerative disorder. In our previous study, using exome sequencing and linkage analysis, two missense mutations of the transglutaminase 6 (TGM6) gene were identified as causative for SCA35. TGM6 encodes transglutaminase 6 (TG6), a member of the transglutaminase family of enzymes that catalyze the formation of a covalent bond between a free amine group and the γ-carboxamide group of protein- or peptide-bound glutamine.

The accumulations of HIF-1α and HIF-2α by JNK and ERK are involved in biphasic effects induced by different levels of arsenite in human bronchial epithelial cells.

The biphasic effects of arsenite, in which low levels of arsenite induce cell proliferation and high levels of arsenite induce DNA damage and apoptosis, apparently contribute to arsenite-induced carcinogenesis. However, the mechanisms underlying this phenomenon are not well understood. In this study, we investigated the effects of different levels of arsenite on cell proliferation, DNA damage and apoptosis as well as on signal transduction pathways in human bronchial epithelial (HBE) cells.

EMT and CSC-like properties mediated by the IKKβ/IκBα/RelA signal pathway via the transcriptional regulator, Snail, are involved in the arsenite-induced neoplastic transformation of human keratinocytes.

Exposure of humans to inorganic arsenic can cause skin cancer. The epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like properties are essential steps in the initiation of human skin cancers; however, the mechanisms of action remain obscure. We have found that, during the neoplastic transformation induced by a low concentration (1.

[Strategies for exome sequence data analysis for discovering genes underlying autosomal recessive disorders].

Introduced in 2009, whole-exome sequencing (WES) is a technology in which target capture methods are used to enrich sequences of coding regions of genes from fragmented total genomic DNA, which is followed by high-throughput sequencing of the captured fragments. As reported, WES has been successfully applied for discovering genes underlying several Mendelian diseases, especially autosomal recessive types. In this review, authors have summarized the main computational strategies which have been applied to identify novel autosomal recessive diseases genes using whole-exome data.

Spinocerebellar ataxia type 23 is an uncommon SCA subtype in the Chinese Han population.

The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative diseases. In 2010, four missense mutations in the prodynorphin (PDYN) gene were found in two families and two sporadic cases of SCA type 23 (SCA23) from the Netherlands. In addition, one missense mutation in PDYN was also found in one sporadic SCA23 case in America in 2012.

Opposed arsenite-mediated regulation of p53-survivin is involved in neoplastic transformation, DNA damage, or apoptosis in human keratinocytes.

Biphasic dose-response relationship induced by environmental agents is often characterized with the effect of low-dose stimulation and high dose inhibition. Some studies showed that arsenite may induce cell proliferation and apoptosis via biphasic dose-response relationship in human cells; however, mechanisms underlying this phenomenon are not well understood. Our present study shows that, for human keratinocytes (HaCaT) cells, a low concentration of arsenite activates extracellular signal-regulated kinases (ERKs), which leads to up-regulation of nuclear factor κB (NF-κB) binding to DNA and to elevated, NF-κB-dependent expression of mot-2 (a p53 inhibitor) and survivin (an inhibitor of apoptosis).

EMT and stem cell-like properties associated with HIF-2α are involved in arsenite-induced transformation of human bronchial epithelial cells.

Background: Arsenic is well-established as a human carcinogen, but the molecular mechanisms leading to arsenic-induced carcinogenesis are complex and elusive. It is not been determined if the epithelial-mesenchymal transition (EMT) and stem cell-like properties contribute in causing to carcinogen-induced malignant transformation and subsequent tumor formation.

Methods: To investigate the molecular mechanisms underlying EMT and the emergence of cancer stem cell-like properties during neoplastic transformation of human bronchial epithelial (HBE) cells induced by chronic exposure to arsenite.

Genetic polymorphisms in CYP2E1: association with schizophrenia susceptibility and risperidone response in the Chinese Han population.

Background: CYP2E1 is a member of the cytochrome P450 superfamily, which is involved in the metabolism and activation of both endobiotics and xenobiotics. The genetic polymorphisms of CYP2E1 gene (Chromosome 10q26.3, Accession Number NC_000010.

Quantitative assessment of the effect of LRRK2 exonic variants on the risk of Parkinson's disease: a meta-analysis.

Leucine-rich repeat kinase 2 (LRRK2, PARK8) gene has attracted considerable attention since the variants in this gene are recognized as the most common cause of Parkinson's disease (PD) so far. A number of association studies concerning variants of LRRK2 gene and PD susceptibility have been conducted in various populations. However, some results were inconclusive.

[Roles of axonal transport affected by K141N mutant HSP22 in the pathogenesis of CMT2L].

Objective: To compare the axonal transport of wild-type (WT) and K141N mutant HSP22 in transfected primary cultured cortical neurons.

Methods: The plasmid (pCAGGS-HA-wtHSP22 or pCAGGS-HA-K141NHSP22) with WT or K141N mutant HSP22 gene and a GFP-expressing plasmid (pEGFP-N1) were co-transfected respectively into primary cultured cortical neurons. The axonal transport of WT and K141N mutant HSP22 was observed.

A novel approach for secretion of heterologous proteins with correct n-terminal processing by using α-factor pre sequence in Pichia pastoris.

Numerous proteins have been secreted in P. pastoris by fusing the target gene with α-factor pre-pro sequence at Kex2 endopeptidase cleavage site. However, in some instances the product cannot be correctly processed due to aberrant cleavage by Kex2 endopeptidase such as aprotinin.

Blockade of p53 by HIF-2α, but not HIF-1α, is involved in arsenite-induced malignant transformation of human bronchial epithelial cells.

Hypoxia-inducible factors (HIFs), which consist of α and β subunits, are transcription factors involved in regulation of a variety of cellular functions. By blocking the function of the tumor suppressor p53, over-expressions of HIFs are linked to carcinogenesis and tumor progression. Inorganic arsenic, a ubiquitous environmental contaminant, is associated with an increased risk of cancer.

Analysis of PLA2G6 gene mutation in sporadic early-onset parkinsonism patients from Chinese population.

Recent studies have shown that PLA2G6 is a causative gene for PARK14-linked autosomal recessive early-onset complicated dystonia-parkinsonism, early-onset parkinsonism with frontotemporal dementia and autosomal recessive early-onset Parkinsonism without added complicated clinical features. In order to investigate the characteristics of PLA2G6 gene mutations in Chinese sporadic early-onset parkinsonism (EOP) patients, we performed polymerase chain reaction and DNA direct sequencing on a cohort of sporadic EOP patients from Chinese population. In this study, we found a novel heterozygous varient (p.

Lower serum UA levels in Parkinson's disease patients in the Chinese population.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, and oxidative stress plays an important role in its pathogenesis. Uric acid (UA) is a product of purine metabolism and is a natural antioxidant that can relieve the oxidative stress that occurs in PD. Recent studies have indicated that the serum UA level are associated with a risk of PD and PD progression of motor symptoms and have proposed UA as a possible biomarker of the underlying pathophysiology of PD.

Regulation of miRNA-21 by reactive oxygen species-activated ERK/NF-κB in arsenite-induced cell transformation.

After acute exposure of cells to arsenic, reactive oxygen species mediate changes in cell behavior, including activation of proliferative signaling. For chronic exposure to arsenic, however, the function of reactive oxygen species in cell transformation remains poorly understood. Although microRNA-21 (miR-21) has been implicated in various aspects of carcinogenesis, its functions and molecular mechanisms in carcinogen-induced tumorigenesis are unclear.

High aspect subdiffraction-limit photolithography via a silver superlens.

Photolithography is the technology of choice for mass patterning in semiconductor and data storage industries. Superlenses have demonstrated the capability of subdiffraction-limit imaging and been envisioned as a promising technology for potential nanophotolithography. Unfortunately, subdiffraction-limit patterns generated by current superlenses exhibited poor profile depth far below the requirement for photolithography.

DNA-PKcs-mediated stabilization of p53 by JNK2 is involved in arsenite-induced DNA damage and apoptosis in human embryo lung fibroblast cells.

When cells encounter genotoxic stress, sensors for DNA lesions stabilize and activate p53; the signals involved, however, are largely unclear. Inorganic arsenite is a ubiquitous environmental contaminant associated with an increased risk of lung and skin damage and cancer. Although DNA double-strand breaks and apoptosis may relate to arsenite-induced damage and carcinogenesis, the mechanism of action remains obscure.

Identification of PRRT2 as the causative gene of paroxysmal kinesigenic dyskinesias.

Paroxysmal kinesigenic dyskinesias is a paroxysmal movement disorder characterized by recurrent, brief attacks of abnormal involuntary movements induced by sudden voluntary movements. Although several loci, including the pericentromeric region of chromosome 16, have been linked to paroxysmal kinesigenic dyskinesias, the causative gene has not yet been identified. Here, we identified proline-rich transmembrane protein 2 (PRRT2) as a causative gene of paroxysmal kinesigenic dyskinesias by using a combination of exome sequencing and linkage analysis.

DNA methylation as a biomarker for neuropsychiatric diseases.

ABSTRACT DNA methylation, which has been investigated extensively recently, has been studied in various human diseases, including cancer, and the analysis of DNA methylation has provided useful biomarkers for diagnosing cancer, monitoring treatment, and predicting the prognosis of cancer. Recently, aberrant DNA methylation has been reported in various neuropsychiatric diseases in both postmortem brains and peripheral blood cells. This review summarizes the current evidence on aberrant DNA methylation in peripheral blood cells from patients with neurodevelopmental, neurodegenerative, and psychiatric disorders, and we propose that DNA methylation could be a novel biomarker for these disorders.

Variant in the 3' region of SNCA associated with Parkinson's disease and serum α-synuclein levels.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. The presence of Lewy bodies is a major pathological change of PD. α-synuclein is the main component of Lewy bodies and is encoded by the SNCA gene.

Magnetic resonance spectroscopy of the cerebellum in patients with spinocerebellar ataxia type 3/Machado-Joseph disease.

Objective: To evaluate the metabolite pattern and the severity in patients with spinocerebellar ataxia type 3/ Machado-Joseph disease (SCA3/MJD) by (1)H magnetic resonance spectroscopy ((1)H-MRS) on different cerebellar regions, including cerebellar vermis, cerebellar peduncles, cerebellar cortex, and dentatum.

Methods: Thirty-six SCA3/MJD patients, and 27 sex, age-matched healthy controls were scanned with (1)H-MRS for N-acetylaspartate (NAA), choline (Cho) and creatine (Cr). We made cerebellar vermis, cerebellar peduncles, cerebellar cortex, and dentatum as the region of interests (ROI), and finally got access to NAA/Cr, Cho/Cr, and NAA/Cho ratios.

Serum concentrations of NSE and S100B in spinocerebellar ataxia type 3/Machado-Joseph disease.

Objective: To determine the neuronal damage or loss and gliosis at the cellular level in spinocerebellar ataxia type 3/Machado-Joseph disease(SCA3/MJD), and evaluate the potential use of neuron-specific enolase (NSE) and protein S 100 B(S100B) serum concentrations as biochemical markers.

Methods: Serum concentrations of NSE and S100B were measured in 102 SCA3/MJD patients and 100 healthy subjects matched by sex and age. The correlations between both markers and age, age of onset, disease duration, CAG repeat size, scores of international cooperative ataxia rating scale(ICARS), and scale for the assessment and rating of ataxia(SARA) were analyzed.

Related factors of ICARS and SARA scores on spinocerebellar ataxia type 3/Machado-Joseph disease.

Objective: To investigate the related factors of international cooperative ataxia rating scale (ICARS) and scale for the assessment and rating of ataxia scores (SARA) in patients with spinocerebellar ataxia type 3/Machado-Joseph disease.

Methods: A total of 126 SCA3/MJD patients were assessed by ICARS and SARA. The relation between ICARS or SARA scores and age of onset, disease duration and CAG repeat size was analyzed.

Spinocerebellar ataxias in mainland China: an updated genetic analysis among a large cohort of familial and sporadic cases.

Objective: To undertake an updated genetic spectrum analysis in patients with hereditary spinocerebellar ataxia (SCA) in mainland China.

Methods: SCA 1, 2, 3, 6, 7, 8, 10, 12, 17 and dentatorubral-pallidoluysian atrophy (DRPLA) nucleotide repeat mutations were detected in 430 families with autosomal dominant SCA (ADCA) and 237 patients with sporadic ataxias by PCR and DNA sequencing. Subsequently, point and Indel (Insertion/deletion) mutation analyses of SCA5, SCA11, SCA13, SCA14, SCA15/16/29, SCA27, SCA31 and SCA35 were detected in 91 families with ADCA and 196 patients with sporadic ataxias excluded from SCA1, 2, 3, 6, 7, 8, 10, 12, 17 and DRPLA genotypes via PCR and Denaturing High Performance Liquid Chromatography (PCR-DHPLC), Multiplex ligation-dependent probe amplification and DNA direct sequencing analysis.

Up-regulation of cyclin D1 by JNK1/c-Jun is involved in tumorigenesis of human embryo lung fibroblast cells induced by a low concentration of arsenite.

Inorganic arsenic, a ubiquitous environmental contaminant, is associated with an increased risk of cancer. There are several hypotheses regarding arsenic-induced carcinogenesis. The mechanism of action remains obscure, although hyper-proliferation of cells is involved.