Role of genomics in translational research for Parkinson's disease.

Research on Parkinson's disease (PD) has made remarkable progress in recent decades, due largely to new genomic technologies, such as high throughput sequencing and microarray analyses. Since the discovery of a linkage of a missense mutation of the α-synuclein (αS) gene to a rare familial dominant form of PD in 1996, positional cloning and characterization of a number of familial PD risk factors have established a hypothesis that aggregation of αS may play a major role in the pathogenesis of PD. Furthermore, dozens of sensitizing alleles related to the disease have been identified by genome wide association studies (GWAS) and meta-GWAS, contributing to a better understanding of the pathological mechanisms of sporadic PD.

NCOA4 transcriptional coactivator inhibits activation of DNA replication origins.

NCOA4 is a transcriptional coactivator of nuclear hormone receptors that undergoes gene rearrangement in human cancer. By combining studies in Xenopus laevis egg extracts and mouse embryonic fibroblasts (MEFs), we show here that NCOA4 is a minichromosome maintenance 7 (MCM7)-interacting protein that is able to control DNA replication. Depletion-reconstitution experiments in Xenopus laevis egg extracts indicate that NCOA4 acts as an inhibitor of DNA replication origin activation by regulating CMG (CDC45/MCM2-7/GINS) helicase.

Diversity of mitochondrial pathology in a mouse model of axonal degeneration in synucleinopathies.

There is mounting evidence for a role of mitochondrial dysfunction in the pathogenesis of α -synucleinopathies such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In particular, recent studies have demonstrated that failure of mitochondrial quality control caused by loss of function of the PTEN-induced kinase 1 (PINK1, PARK6) Parkin (PARK2) pathway may be causative in some familial PD. In sporadic PD, α -synuclein aggregation may interfere with mitochondrial function, and this might be further exacerbated by leucine-rich repeat kinase 2 (LRRK2).

Diverse systems for pheromone perception: multiple receptor families in two olfactory systems.

Traditionally, the olfactory epithelium is considered to recognize conventional odors, while the vomeronasal organ detects pheromones. However, recent advances suggest that vertebrate pheromones can also be detected by the olfactory epithelium. In the vomeronasal organ and the olfactory epithelium, structurally distinct multiple receptor families are expressed.

The toxic effect of Alzheimer amyloid protein precursor overexpressed in the neuroblastoma cell line NB-1 on neurite outgrowth.

The neuroblastoma cell line NB-1 is induced to start neurite outgrowth by dibutyryl cyclic AMP (Bt2cAMP). To study the function of Alzheimer amyloid protein precursor (APP), a stable cell line overexpressing APP was established by cDNA transfection. The APP cDNA was driven by the cytomegalovirus early gene promoter.

Point mutations in the upstream region of the alpha-galactosidase A gene exon 6 in an atypical variant of Fabry disease.

Single point mutations in the upstream region of exon 6 of the alpha-galactosidase A gene were found in two Japanese cases of the cardiac form of Fabry disease; 301Arg----Gln (902G----A) in a case that has already been published and 279Gln----Glu (835C----G) in a new case. They both expressed markedly low, but significant, amounts of residual activity in COS-1 cells. In contrast, two unrelated cases with classic Fabry disease were found to have different point mutations, which showed a complete loss of enzyme activity in a transient expression assay; 328Gly----Arg (982G----A) in the downstream region of exon 6 in one case and two combined mutations, 66Glu----Gln (196G----C)/112Arg----Cys (334C----T), in exon 2 in the other.

Electron transfer reactions in the NADPH oxidase system of neutrophils--involvement of an NADPH-cytochrome c reductase in the oxidase system.

Membrane-bound NADPH oxidase of pig blood neutrophils was solubilized with heptylthioglucoside in a high yield. The solubilized preparation from myristate-stimulated cells (sample S) showed high O2- generating activity, and the preparation from resting cells (sample R) had no activity, but the two samples had equal amounts of flavins and cytochrome b-558 (cyt b-558). The electron transfer reactions to exogenous cytochrome c (cyt c) or cyt b-558 in samples S and R were examined.

Antibodies to translation products of the pre-S1 and pre-S2 regions of the envelope gene of hepatitis B virus in fulminant hepatitis B.

Sera from 11 patients with fulminant hepatitis B were tested for antibodies to translation products of the pre-S1 and pre-S2 regions of hepatitis B virus of IgM, IgA and IgG classes, as well as of IgA1, IgA2 and SIgA, with solid-phase enzyme immunoassays using native viral polypeptides. Antibodies to pre-S1 region product of IgM and/or IgA class were detected invariably in six patients who still had detectable hepatitis B surface antigen in serum at the time of clinical presentation. The remaining five patients who had lost HBsAg at presentation had antibodies to pre-S region products of various immunoglobulin classes in higher titers.

Native pyrophosphate gel analysis of smooth muscle myosin phosphorylated with protein kinase C.

We have shown that the phosphorylation of smooth muscle regulatory myosin light chain (L20) with myosin light chain kinase (MLCK) produces faster moving bands (GMP1: heterodimer myosin with 1 unphosphorylated L20 and 1 mono-phosphorylated L20, GMP2: homodimer myosin with 2 mono-phosphorylated L20S) on native pyrophosphate polyacrylamide gel electrophoresis (PP1 PAGE) (J. Biochem. 100, 259-268, 1986; J.