Molecular dynamics simulation of diffusion of hydrogen in binary hydrogen–tetrahydrofuran hydrate

The binary structure II hydrogen–tetrahydrofuran (THF) hydrate was studied with molecular dynamics simulation. The simulations were carried out at 300, 310 K and 10.1 MPa, and with various contents of hydrogen and THF. The migrations of hydrogen molecules from cage to cage were observed. The migration process of hydrogen was also analysed, and the diffusion coefficients of hydrogen in the hydrate were calculated. The calculated diffusion coefficients qualitatively agreed with the experimental data. Double and quintet occupancies of hydrogen molecules were observed in the small and large cages, respectively, without changing the hydrate structure.     

Mutations in SERPINB7, Encoding a Member of the Serine Protease Inhibitor Superfamily,Cause Nagashima-type Palmoplantar Keratosis

“Nagashima-type” palmoplantar keratosis (NPPK) is an autosomal recessive nonsyndromic diffuse palmoplantar keratosis characterized by well-demarcated diffuse hyperkeratosis with redness, expanding on to the dorsal surfaces of the palms and feet and the Achilles tendon area. Hyperkeratosis in NPPK is mild and nonprogressive, differentiating NPPK clinically from Mal de Meleda. We performed whole-exome and/or Sanger sequencing analyses of 13 unrelated NPPK individuals and identified biallelic putative loss-of-function mutations in SERPINB7, which encodes a cytoplasmic member of the serine protease inhibitor superfamily. We identified a major causative mutation of c.796C>T (p.Arg266^∗) as a founder mutation in Japanese and Chinese populations. SERPINB7 was specifically present in the cytoplasm of the stratum granulosum and the stratum corneum (SC) of the epidermis. All of the identified mutants are predicted to cause premature termination upstream of the reactive site, which inhibits the proteases, suggesting a complete loss of the protease inhibitory activity of SERPINB7 in NPPK skin. On exposure of NPPK lesional skin to water, we observed a whitish spongy change in the SC, suggesting enhanced water permeation into the SC due to overactivation of proteases and a resultant loss of integrity of the SC structure. These findings provide an important framework for developing pathogenesis-based therapies for NPPK.     

Synthesis and properties of thymidines with six-membered amide bridge

Artificial thymidine monomers possessing amide or N-methylamide bridges were designed, synthesized, and introduced into oligonucleotides. UV-melting experiments showed that these oligonucleotides preferred single-stranded RNA (ssRNA) to single-stranded DNA (ssDNA) in duplex formation. Both amide- and N-methylamide-modified oligonucleotides led to a significant increase in the binding affinity to ssRNA by up to +4.7 and +3.7 °C of the T_m value per modification, respectively, compared with natural oligonucleotide. In addition, their oligonucleotides showed high stability against 3′-exonuclease.     

The obesity epidemic and changes in self‐report biases in BMI

Objective:

To assess time trends in measurement error of BMI and the sensitivity/specificity of classifying weight status in the United States by analyzing the difference in BMI between self‐reported and measured height and weight.

Design and Methods:

Data from 18,394 respondents aged 20‐89 years from the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2008 were analyzed. Multiple linear regression and logistic regression models estimated trends in reporting bias and misclassification of weight status by BMI categories, sex, age, and racial/ethnic groups, adjusting for the sampling design.

Results:

We find no evidence that there are time trends in the accuracy of self‐report by BMI categories, sex, age, or racial/ethnic groups. The well‐known downward bias in self‐report has remained stable over the last decade; approximately one in six to seven obese individuals were misclassified as nonobese due to underestimation of BMI.

Conclusion:

Increases in obesity rates based on self‐reported height and weight are likely to reflect actual weight increases and are not inflated by changes in reporting accuracy.     

Dnajb8, a Member of the Heat Shock Protein 40 Family Has a Role in the Tumor Initiation and Resistance to Docetaxel but Is Dispensable for Stress Response

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined by their abilities of tumor initiation, self-renewal and differentiation. In a previous study, we showed by gene knockdown using siRNA and gene overexpression experiments that Dnaj (Hsp40) homolog, subfamily B, member 8 (DNAJB8), a role in the maintenance, of renal cell carcinoma CSCs/CICs. In the present study, we established Dnajb8 knockout (KO) renal cell carcinoma (RCC) line cells (RenCa cells) and analyzed the cells to confirm the function of Dnajb8 in RCC CSCs/CICs. Dnajb8 KO cells showed reduced ratios of side population cells and reduced sphere forming ability. An in vivo single cell tumor initiation assay revealed that the numbers of CSCs/CICs were 3 in 4 wild-type RenCa cells and 1 in 4 Dnajb8 KO cells. Dnajb8 KO cells showed sensitivity to Docetaxel. On the other hand, Dnajb8 KO cells did not show any sensitivities to stresses including low pH, low glucose, heat shock and sensitivity to cisplatin. The results indicate that Dnajb8 has a role in tumor initiation, side population ratio and sphere formation but it is dispensable for stress responses.     

Temperature dependence on the pesticide sampling rate of polar organic chemical integrative samplers (POCIS)

Laboratory experiments were performed to determine the sampling rates of pesticides for the polar organic chemical integrative samplers (POCIS) used in Japan. The concentrations of pesticides in aquatic environments were estimated from the accumulated amounts of pesticide on POCIS, and the effect of water temperature on the pesticide sampling rates was evaluated. The sampling rates of 48 pesticides at 18, 24, and 30 °C were obtained, and this study confirmed that increasing trend of sampling rates was resulted with increasing water temperature for many pesticides.     

Structure-activity relationship studies of Bz amide-containing α-GalCer derivatives as natural killer T cell modulators

Abstract

CD1d is a non-polymorphic antigen-presenting glycoprotein that recognizes glycolipids as ligands. Ligands bind to the hydrophobic grooves of CD1d, and the resulting ligand-CD1d complexes activate natural killer T (NKT) cells by means of T cell receptor recognition, leading to the secretion of various cytokines. However, details of the ligand recognition mechanism of a large hydrophobic ligand binding pocket and the relationship between cytokine induction and ligand structure are unclear. We report the synthesis of α-GalCer derivatives containing a Bz amide group having various substituting groups in the ceramide moiety, and the analysis of the structure-activity relationships. The assays reveal that the Bz amide-containing CD1d ligands function as NKT cell modulators displaying Th2 cytokine biasing responses. Furthermore, molecular dynamics simulation studies suggest that the phenyl groups can interact with the aromatic amino acid residues in the lipid binding pocket of CD1d.     

Differences in flowering phenology,architecture, sexual expression and resource allocation between a heavily haired and a lightly haired nettle population: relationships with sika deer

Plant Ecology - Japanese stinging nettles, Urtica thunbergiana, in Nara Park (660 ha), central Japan, where several hundred sika deer Cervus nippon have been protected for...     

Oncostatin M induces upregulation of claudin-2 in rodent hepatocytes coinciding with changes in morphology and function of tight junctions

In rodent livers, integral tight junction (TJ) proteins claudin-1, -2, -3, -5 and -14 are detected and play crucial roles in the barrier to keep bile in bile canaculi away from the blood circulation. Claudin-2 shows a lobular gradient increasing from periportal to pericentral hepatocytes, whereas claudin-1 and -3 are expressed in the whole liver lobule. Although claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells, the physiological functions and regulation of claudin-2 in hepatocytes remain unclear. Oncostatin M (OSM) is a multifunctional cytokine implicated in the differentiation of hepatocytes that induces formation of E-cadherin-based adherens junctions in fetal hepatocytes. In this study, we examined whether OSM could induce expression and function of claudin-2 in rodent hepatocytes, immortalized mouse and primary cultured proliferative rat hepatocytes. In the immortalized mouse and primary cultured proliferative rat hepatocytes, treatment with OSM markedly increased mRNA and protein of claudin-2 together with formation of developed networks of TJ strands. The increase of claudin-2 enhanced the paracellular barrier function which depended on molecular size. The increase of claudin-2 expression induced by OSM in rodent hepatocytes was regulated through distinct signaling pathways including PKC. These results suggest that expression of claudin-2 in rodent hepatocytes may play a specific role as controlling the size of paracellular permeability in the barrier to keep bile in bile canaculi.     

Transient expression of bone morphogenic protein-2 in acute liver injury by carbon tetrachloride

Acute liver injury induced by administration of carbon tetrachloride (CCl4) was shown to be a model of wound-repair in rat liver. Albumin gene expression was significantly reduced at 24 h post injection with CCl4, but recovered at 48 h. We also observed significant and transient expression of bone morphogenic protein-2 (BMP-2) at 6-24 h post treatment. This expression was also shown with depletion of Kupffer cell by GdCl3, and immunostaining with anti-BMP-2 antibody showed BMP-2-producing cells interspersed in intralobular spaces of injured liver. These observations suggest that BMP-2 secreted from oval-like cells plays important roles in the wound healing response of injured liver.