HSP‐enriched properties of extracellular vesicles involve survival of metastatic oral cancer cells

Cancer cells often secrete extracellular vesicles (EVs) that carry heat shock proteins (HSPs) with roles in tumor progression. Oral squamous cell carcinoma (OSCC) belongs to head and neck cancers (HNC) whose lymph-node-metastases often lead to poor prognosis. We have examined the EV proteome of OSCC cells and found abundant secretion of HSP90-enriched EVs in lymph-node-metastatic OSCC cells. Double knockdown of HSP90α and HSP90β, using small interfering RNA significantly reduced the survival of the metastatic OSCC cells, although single knockdown of each HSP90 was ineffective. Elevated expression of these HSP90 family members was found to correlate with poor prognosis of HNC cases. Thus, elevated HSP90 levels in secreted vesicles are potential prognostic biomarkers and therapeutic targets in metastatic OSCC

Gene Expression Signatures That Predict Radiation Exposure in Mice and Humans

BACKGROUND: The capacity to assess environmental inputs to biological phenotypes is limited by methods that can accurately and quantitatively measure these contributions. One such example can be seen in the context of exposure to ionizing radiation. METHODS AND FINDINGS: We have made use of gene expression analysis of peripheral blood (PB) mononuclear cells to develop expression profiles that accurately reflect prior radiation exposure. We demonstrate that expression profiles can be developed that not only predict radiation exposure in mice but also distinguish the level of radiation exposure, ranging from 50 cGy to 1,000 cGy. Likewise, a molecular signature of radiation response developed solely from irradiated human patient samples can predict and distinguish irradiated human PB samples from nonirradiated samples with an accuracy of 90%, sensitivity of 85%, and specificity of 94%. We further demonstrate that a radiation profile developed in the mouse can correctly distinguish PB samples from irradiated and nonirradiated human patients with an accuracy of 77%, sensitivity of 82%, and specificity of 75%. Taken together, these data demonstrate that molecular profiles can be generated that are highly predictive of different levels of radiation exposure in mice and humans. CONCLUSIONS: We suggest that this approach, with additional refinement, could provide a method to assess the effects of various environmental inputs into biological phenotypes as well as providing a more practical application of a rapid molecular screening test for the diagnosis of radiation exposure

Criterion and Construct Validity of the CogState Schizophrenia Battery in Japanese Patients with Schizophrenia

BACKGROUND: The CogState Schizophrenia Battery (CSB), a computerized cognitive battery, covers all the same cognitive domains as the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery but is briefer to conduct. The aim of the present study was to evaluate the criterion and construct validity of the Japanese language version of the CSB (CSB-J) in Japanese patients with schizophrenia. METHODOLOGY/PRINCIPAL FINDINGS: Forty Japanese patients with schizophrenia and 40 Japanese healthy controls with matching age, gender, and premorbid intelligence quotient were enrolled. The CSB-J and the Brief Assessment of Cognition in Schizophrenia, Japanese-language version (BACS-J) were performed once. The structure of the CSB-J was also evaluated by a factor analysis. Similar to the BACS-J, the CSB-J was sensitive to cognitive impairment in Japanese patients with schizophrenia. Furthermore, there was a significant positive correlation between the CSB-J composite score and the BACS-J composite score. A factor analysis showed a three-factor model consisting of memory, speed, and social cognition factors. CONCLUSIONS/SIGNIFICANCE: This study suggests that the CSB-J is a useful and rapid automatically administered computerized battery for assessing broad cognitive domains in Japanese patients with schizophrenia

Genetic and environmental contributions to variation in the inclination of human mandibular molars

Copyright © 2004 Japanese Orthodontic SocietyEguchi Shosei, Grant C Townsend, Toby Hughes and Kasai Kazutakahttp://www.jos.gr.jp/mz/Jjos/E/je63-E4-95.ht

Genetic contribution to dental arch size variation in Australian twins

Copyright © 2004 Elsevier Ltd All rights reserved.The aim of this study was to quantify the relative contributions of genetic and environmental factors to variations in dental arch breadth, length and palatal height in a sample of Australian twins, and to estimate heritabilities using modern model-fitting methods. Dental casts of 20 male and 24 female monozygous (MZ) twin pairs, 17 male and 8 female dizygous (DZ) twin pairs, and 9 opposite-sexed DZ twin pairs were selected from the collection of records of twins housed at the Adelaide Dental School. The mean ages of subjects were 15.8 +/- 3.5 years (MZ) and 17.0 +/- 4.7 years (DZ). Dental casts were scanned using a contact-type 3D scanner, PICZA interfaced to a personal computer running 3D-Rugle3 software. Data were subjected to univariate genetic analysis with the structural equation modelling package, Mx, using the normal assumptions of the twin model. A model incorporating additive genetic (A) and unique environmental (E) variation was found to be the most parsimonious for dental arch breadth and length, and palatal height. Estimates of heritability for dental arch breadth ranged from 0.49 to 0.92, those for arch length from 0.86 to 0.94, and those for palatal height were 0.80 and 0.81, respectively. These results indicate a high genetic contribution to the variation in dental arch dimensions in mainly teenage twins.Shosei Eguchi, Grant C. Townsend, Lindsay C. Richards, Toby Hughes, Kazutaka Kasa

Low frequency of spontaneous rearrangements during plasmid incorporation in CHO-K1 mutant cells defective in DNA repair

pLrec plasmid DNA was introduced into Chinese hamster cell lines defective in DNA repair (Pa13, Pb4, xrs6) and the parental CHO-K1 cell line. Clones with stable integrated plasmid were isolated and integrity of the incorporated DNA was checked by Southern blotting and PCR. Intact pLrec plasmid was found in 11% of the isolated CHO-K1 clones. In contrast, intact plasmid copies were found in 68.8%, 50%, 35.7% clones of Pa13, Pb4 and xrs6 cell lines, respectively. We conclude that certain DNA repair defects may facilitate intact plasmid integration. The higher frequency of integration of the intact vector into the genome of cell lines defective in DNA repair as compared to the parental cell line points to two possibilities, not mutually exclusive: (1) these cells possess a mechanism that facilitates the process of plasmid incorporation and hence, plasmid DNA is incorporated into the genome before extrachromosomal recombination takes place; (2) the vector is inserted into a less recombination prone site in the genome