Molecular Genetics of Conjunctival Melanoma and Prognostic Value of TERT Promoter Mutation Analysis

The aim of this study was exploration of the genetic background of conjunctival melanoma (CM) and correlation with recurrent and metastatic disease. Twenty-eight CM from the Rotterdam Ocular Melanoma Study group were collected and DNA was isolated from the formalin-fixed paraffin embedded tissue. Targeted next-generation sequencing was performed using a panel covering GNAQ, GNA11, EIF1AX, BAP1, BRAF, NRAS, c-KIT, PTEN, SF3B1, and TERT genes. Recurrences and metastasis were present in eight (29%) and nine (32%) CM cases, respectively. TERT promoter mutations were most common (54%), but BRAF (46%), NRAS (21%), BAP1 (18%), PTEN (14%), c-KIT (7%), and SF3B1 (4%) mutations were also observed. No mutations in GNAQ, GNA11, and EIF1AX were found. None of the mutations was significantly associated with recurrent disease. Presence of a TERT promoter mutation was associated with metastatic disease (p-value = 0.008). Based on our molecular findings, CM comprises a separate entity within melanoma, although there are overlapping molecular features with uveal melanoma, such as the presence of BAP1 and SF3B1 mutations. This warrants careful interpretation of molecular data, in the light of clinical findings. About three quarter of CM contain drug-targetable mutations, and TERT promoter mutations are correlated to metastatic disease in CM.     

From paper to pixels: A comparison of paper and computer formats in psychological assessment

Internet based data collection methods have many advantages for psychological assessment when compared with more traditional paper formats, including, reduced costs, and greater convenience for both the researcher and the participant. However, prior to the wide-spread adoption of these methods, equivalence with paper tests formats must be established. The present study compared questionnaire data from the computer with that from a traditional paper format in a sample of college students both directly and through an opinion survey. Three types of questionnaires that represent distinct areas commonly assessed in psychological research included: quality of life (SF-36), depression (BDI-II) and personality (NEO). A within-subjects design counterbalanced order across the computer and paper formats. Overall the findings showed no differences for the Neuroticism and Extraversion facts of the NEO, for the BDI and for the subscales and composite scores of the SF-36. Significant differences were found between the paper and computer formats for the Openness, Agreeableness, and Conscientiousness facets of the NEO. Additionally, the computer was perceived to be convenient, user-friendly, comfortable, and secure. Results suggest that a computerized format is an efficient way to conduct quality of life research, especially for the assessment of distress levels and quality of life.     

Repair materials and techniques for concrete structures in nuclear power plants

The paper summaries portions of work of the Structural Aging Program, sponsored by the Nuclear Regulatory Commission (NRC). The paper addresses the assessment and repair of concrete structures in nuclear power plants. It presents the results of a survey of the the nuclear power plants in the United States to identify susceptible concrete components, rates of occurrence of deterioration, and to determine the durability of repairs. The paper describes deterioration mechanisms and discusses their effect. Repair techniques are described. Evaluation techniques and nondestructive test techniques are also discussed.     

Comparison of transdermal versus oral estradiol on endometrial receptivity

OBJECTIVE: To compare the effects of oral micronized E2 with transdermal E2 on endometrial receptivity in women undergoing oocyte donation. DESIGN: Prospective, randomized, crossover trial. Serum E2 and P concentrations were measured on cycle days 14 and 22 (luteal day +8). Endometrial biopsies were obtained on day 22 and read in a blinded fashion for histology and beta-3-integrin expression. SETTING: University-based donor oocyte program. PATIENTS: Twenty-seven patients presenting for donor oocytes. MAIN OUTCOME MEASURES: Endometrial histology and beta-3-integrin expression. RESULTS: The endometrial glandular histology in women given oral micronized E2 was delayed by a mean of 1.6 days in comparison to that of women given transdermal E2. Seventy percent of women given oral E2 displayed a lag > or = 4 days whereas 29.6% given transdermal E2 displayed a similar lag. Serum E2 levels were 1,194 +/- 108.8 pg/mL (mean +/- SEM; conversion factor to SI unit, 3.671) in women on oral micronized E2 and 117.4 +/- 14.0 pg/mL in those on transdermal E2. CONCLUSION: The supraphysiologic serum E2 levels associated with oral micronized E2 may have a deleterious impact on endometrial receptivity. The development of more physiologic hormone replacement protocols may enhance endometrial receptivity and lead to improved clinical pregnancy rates.     

Expression of gap junctions in cultured rat L6 cells during myogenesis

Although gap junctions are absent from adult skeletal muscle, they have been described in embryonic and neonatal rat skeletal muscle and in cultured rat myoblasts. In order to determine the precise developmental expression and molecular composition of gap junctions during myogenesis, RNA was isolated from cultures of rat L6 myoblasts and examined using Northern blot analysis with cDNA probes specific for connexin32 and connexin43. Connexin32 mRNA could not be detected in rat myoblast and myotube samples. However, connexin43 mRNA was expressed at high levels in cycling L6 myoblasts and this expression decreased by approximately 60% in L6 myotubes following fusion. Immunofluorescent localization with an antibody specific for connexin43 confirmed the accumulation of connexin43 protein in membranes shared between adjacent myoblasts at 12 hr of culture. By 24 hr of culture, connexin43 disappeared from most cells, only to reappear at 36 hr at a low level that was maintained through 72 hr in culture. Although most myoblasts in these cultures expressed connexin43, myotubes expressed little or no membrane-associated connexin43. Dye transfer experiments established that, at 12 hr of culture, the majority of myoblasts were dye coupled suggesting that connexin43 protein is assembled into functional gap junctions. At 24 hr, the number of coupled cells decreased slightly, while at 48 hr, most of the myoblasts were not dye coupled. These results demonstrate that the expression of connexin43 is temporally correlated with myoblast fusion and may play a role in this process.     

Human IgE, IgG subclass, and IgM responses to worm and egg antigens in schistosomiasis haematobium: a 12-month study of reinfection in Cameroonian children

Methylglyoxal (MG), a dicarbonyl compound produced by the fragmentation of triose phosphates, forms advanced glycation endproducts (AGEs) in vitro. Glyoxalase-I catalyzes the conversion of MG to S-D-lactoylglutathione, which in turn is converted to D-lactate by glyoxalase-II. To evaluate directly the effect of glyoxalase-I activity on intracellular AGE formation, GM7373 endothelial cells that stably express human glyoxalase-I were generated. Glyoxalase-I activity in these cells was increased 28-fold compared to neo-transfected control cells (21.80+/-0.1 vs. 0. 76+/-0.02 micromol/min/mg protein, n = 3, P < 0.001). In neo-transfected cells, 30 mM glucose incubation increased MG and D-lactate concentration approximately twofold above 5 MM (35.5+/-5.8 vs. 19.6+/-1.6, P < 0.02, n = 3, and 21.0+/-1.3 vs. 10.0+/-1.2 pmol/ 10(6) cells, n = 3, P < 0.001, respectively). In contrast, in glyoxalase-I-transfected cells, 30 mM glucose incubation did not increase MG concentration at all, while increasing the enzymatic product D-lactate by > 10-fold (18.9+/-3.2 vs. 18.4+/- 5.8, n = 3, P = NS, and 107.1+/-9.0 vs. 9.4+/-0 pmol/10(6) cells, n = 3, P < 0.001, respectively). After exposure to 30 mM glucose, intracellular AGE formation in neo cells was increased 13.6-fold (2.58+/-0.15 vs. 0.19+/-0.03 total absorbance units, n = 3, P < 0.001). Concomitant with increased intracellular AGEs, macromolecular endocytosis by these cells was increased 2.2-fold. Overexpression of glyoxalase-I completely prevented both hyperglycemia-induced AGE formation and increased macromolecular endocytosis.     

Retrieving for rehearsal: An analysis of active rehearsal in children's memory.

Two experiments with 96 2nd graders and 24 6th graders explored the operation of retrieval processes in Ss' active rehearsal strategies. Both experiments used free-recall tasks, in which Ss were given instructions in active rehearsal as well as supports that might facilitate the retrieval operation and thus enhance both rehearsal and recall performance. In Exp I, 2nd and 6th graders were given visual or auditory access to an 18-item stimulus-word list. Results show that, by providing 2nd graders with an opportunity to view previously presented words, rehearsal activity and recall increased substantially, whereas the performance of the 6th graders was not affected. In Exp II, presentation time and visual access to a similar 18-word list were manipulated for 2nd graders. Results show that the provision of extra time for an item enabled Ss to execute a more active rehearsal strategy. Extra time had only minimal effects on recall, except when it was combined with visual access to the items. Findings suggest that retrieval per se is not necessary for the beneficial effects of active rehearsal, if other procedures can be followed to permit the juxtaposition of several items in rehearsal. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)