Plasma lipid profiling of different types of hepatic fibrosis induced by carbon tetrachloride and lomustine in rats

Supplementary tables. Table S1. Class, m/z, retention time, ion of detected and identified lipid molecules, and determined their fatty side chains. Table S2. Normalized levels of lipid molecules in individual samples. Table S3. Fold change and p-value of the levels of lipid molecules. (XLSX 317 kb

Bilateral Renal Cell Carcinoma and its Treatment

A report is presented on two cases of bilateral renal cell carcinoma together with a review of the literature. Bilateral renal cell carcinoma is rare and there is much controversy concerning its treatment. Our current experience supports conservative therapy for bilateral renal cell carcinoma

Comments on Quantum Aspects of Three-Dimensional de Sitter Gravity

We investigate the quantum aspects of three-dimensional gravity with a positive cosmological constant. The reduced phase space of the three-dimensional de Sitter gravity is obtained as the space which consists of the Kerr-de Sitter space-times and their Virasoro deformations. A quantization of the phase space is carried out by the geometric quantization of the coadjoint orbits of the asymptotic Virasoro symmetries. The Virasoro algebras with real central charges are obtained as the quantum asymptotic symmetries. The states of globally de Sitter and point particle solutions become the primary states of the unitary irreducible representations of the Virasoro algebras. It is shown that those states are perturbatively stable at the quantum level. The Virasoro deformations of these solutions correspond to the excited states in the unitary irreducible representations. In view of the dS/CFT correspondence, we also study the relationship between the Liouville field theory obtained by a reduction of the SL(2;$\mathbb{C}$) Chern-Simons theory and the three-dimensional gravity both classically and quantum mechanically. In the analyses of the both theories, the Kerr-de Sitter geometries with nonzero angular momenta do not give the unitary representations of the Virasoro algebras.Comment: 25 pages, LaTeX, typos corrected. References are adde

μ1B, a novel adaptor medium chain expressed in polarized epithelial cells11The nucleotide sequences reported in this paper have been submitted to GenBank with accession numbers AF020797 (human μ1B) and AF067146 (mouse μ1B).

AbstractThe apical and basolateral plasma membrane domains of polarized epithelial cells contain distinct sets of integral membrane proteins. Biosynthetic targeting of proteins to the basolateral plasma membrane is mediated by cytosolic tail determinants, many of which resemble signals involved in the rapid endocytosis or lysosomal targeting. Since these signals are recognized by adaptor proteins, we hypothesized that there could be epithelial-specific adaptors involved in polarized sorting. Here, we report the identification of a novel member of the adaptor medium chain family, named μ1B, which is closely related to the previously described μ1A (79% amino acid sequence identity). Northern blotting and in situ hybridization analyses reveal the specific expression of μ1B mRNA in a subset of polarized epithelial and exocrine cells. Yeast two-hybrid analyses show that μ1B is capable of interacting with generic tyrosine-based sorting signals. These observations suggest that μ1B may be involved in protein sorting events specific to polarized cells

Trk-fused gene (TFG) regulates pancreatic beta cell mass and insulin secretory activity

The Trk-fused gene (TFG) is reportedly involved in the process of COPII-mediated vesicle transport and missense mutations in TFG cause several neurodegenerative diseases including hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P). The high coincidence ratio between HMSN-P and diabetes mellitus suggests TFG to have an important role(s) in glucose homeostasis. To examine this possibility, β-cell specific TFG knockout mice (βTFG KO) were generated. Interestingly, βTFG KO displayed marked glucose intolerance with reduced insulin secretion. Immunohistochemical analysis revealed smaller β-cell masses in βTFG KO than in controls, likely attributable to diminished β-cell proliferation. Consistently, β-cell expansion in response to a high-fat, high-sucrose (HFHS) diet was significantly impaired in βTFG KO. Furthermore, glucose-induced insulin secretion was also markedly impaired in islets isolated from βTFG KO. Electron microscopic observation revealed endoplasmic reticulum (ER) dilatation, suggestive of ER stress, and smaller insulin crystal diameters in β-cells of βTFG KO. Microarray gene expression analysis indicated downregulation of NF-E2 related factor 2 (Nrf2) and its downstream genes in TFG depleted islets. Collectively, TFG in pancreatic β-cells plays a vital role in maintaining both the mass and function of β-cells, and its dysfunction increases the tendency to develop glucose intolerance.This study was partly supported by a Grant-in-Aid for Research Activity Start-up (JSPS KAKENHI Grant Number JP15H06427) (to T.Y.) from the Ministry of Education, Science, Sports and Culture, Japan, and grants from Mitsubishi Tanabe Pharma (to T.Y.), Novartis Pharma (to T.Y.), Takeda Science Foundation (to Y.N.), Asahi Life Foundation (to Y.N.) and The Uehara Memorial Foundation (to Y.N.)

Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor

AP-3 is a member of the adaptor protein (AP) complex family that regulates the vesicular transport of cargo proteins in the secretory and endocytic pathways. There are two isoforms of AP-3: the ubiquitously expressed AP-3A and the neuron-specific AP-3B. Although the physiological role of AP-3A has recently been elucidated, that of AP-3B remains unsolved. To address this question, we generated mice lacking μ3B, a subunit of AP-3B. μ3B−/− mice suffered from spontaneous epileptic seizures. Morphological abnormalities were observed at synapses in these mice. Biochemical studies demonstrated the impairment of γ-aminobutyric acid (GABA) release because of, at least in part, the reduction of vesicular GABA transporter in μ3B−/− mice. This facilitated the induction of long-term potentiation in the hippocampus and the abnormal propagation of neuronal excitability via the temporoammonic pathway. Thus, AP-3B plays a critical role in the normal formation and function of a subset of synaptic vesicles. This work adds a new aspect to the pathogenesis of epilepsy

XAB2, a novel tetratricopeptide repeat protein, involved in transcription-coupled repair and transcription.

Nucleotide excision repair is a highly versatile DNA repair system responsible for elimination of a wide variety of lesions from the genome. It is comprised of two subpathways: transcription-coupled repair that accomplishes efficient removal of damage blocking transcription and global genome repair. Recently, the basic mechanism of global genome repair has emerged from biochemical studies. However, little is known about transcription-coupled repair in eukaryotes. Here we report the identification of a novel protein designated XAB2 (XPA-binding protein 2) that was identified by virtue of its ability to interact with XPA, a factor central to both nucleotide excision repair subpathways. The XAB2 protein of 855 amino acids consists mainly of 15 tetratricopeptide repeats. In addition to interacting with XPA, immunoprecipitation experiments demonstrated that a fraction of XAB2 is able to interact with the transcription-coupled repair-specific proteins CSA and CSB as well as RNA polymerase II. Furthermore, antibodies against XAB2 inhibited both transcription-coupled repair and transcription in vivo but not global genome repair when microinjected into living fibroblasts. These results indicate that XAB2 is a novel component involved in transcription-coupled repair and transcription

Applications of Soft Computing in Engineering Problems

Non

Complete and Incomplete Genome Packaging of Influenza A and B Viruses

The genomes of influenza A and B viruses comprise eight segmented, single-stranded, negative-sense viral RNAs (vRNAs). Although segmentation of the virus genome complicates the packaging of infectious progeny into virions, it provides an evolutionary benefit in that it allows viruses to exchange vRNAs with other strains. Influenza A viruses are believed to package their eight different vRNAs in a specific manner. However, several studies have shown that many viruses are noninfectious and fail to package at least one vRNA. Therefore, the genome-packaging mechanism is not fully understood. In this study, we used electron microscopy to count the number of ribonucleoproteins (RNPs) inside the virions of different influenza A and B virus strains. All eight strains examined displayed eight RNPs arranged in a “7+1” configuration in which a central RNP was surrounded by seven RNPs. Three-dimensional analysis of the virions showed that at least 80% of the virions packaged all eight RNPs; however, some virions packaged only five to seven RNPs, with the exact proportion depending on the strain examined. These results directly demonstrate that most viruses package eight RNPs, but some do indeed package fewer. Our findings support the selective genome-packaging model and demonstrate the variability in the number of RNPs incorporated by virions, suggesting that the genome-packaging mechanism of influenza viruses is more flexible than previously thought