A WXW Motif Is Required for the Anticancer Activity of the TAT-RasGAP317-326 Peptide.

TAT-RasGAP317-326, a cell-permeable 10-amino acid-long peptide derived from the N2 fragment of p120 Ras GTPase-activating protein (RasGAP), sensitizes tumor cells to apoptosis induced by various anticancer therapies. This RasGAP-derived peptide, by targeting the deleted in liver cancer-1 (DLC1) tumor suppressor, also hampers cell migration and invasion by promoting cell adherence and by inhibiting cell movement. Here, we systematically investigated the role of each amino acid within the RasGAP317-326 sequence for the anticancer activities of TAT-RasGAP317-326. We report here that the first three amino acids of this sequence, tryptophan, methionine, and tryptophan (WMW), are necessary and sufficient to sensitize cancer cells to cisplatin-induced apoptosis and to reduce cell migration. The WMW motif was found to be critical for the binding of fragment N2 to DLC1. These results define the interaction mode between the active anticancer sequence of RasGAP and DLC1. This knowledge will facilitate the design of small molecules bearing the tumor-sensitizing and antimetastatic activities of TAT-RasGAP317-326.

Research resource: the dynamic transcriptional profile of sertoli cells during the progression of spermatogenesis.

Sertoli cells (SCs), the only somatic cells within seminiferous tubules, associate intimately with developing germ cells. They not only provide physical and nutritional support but also secrete factors essential to the complex developmental processes of germ cell proliferation and differentiation. The SC transcriptome must therefore adapt rapidly during the different stages of spermatogenesis. We report comprehensive genome-wide expression profiles of pure populations of SCs isolated at 5 distinct stages of the first wave of mouse spermatogenesis, using RNA sequencing technology. We were able to reconstruct about 13 901 high-confidence, nonredundant coding and noncoding transcripts, characterized by complex alternative splicing patterns with more than 45% comprising novel isoforms of known genes. Interestingly, roughly one-fifth (2939) of these genes exhibited a dynamic expression profile reflecting the evolving role of SCs during the progression of spermatogenesis, with stage-specific expression of genes involved in biological processes such as cell cycle regulation, metabolism and energy production, retinoic acid synthesis, and blood-testis barrier biogenesis. Finally, regulatory network analysis identified the transcription factors endothelial PAS domain-containing protein 1 (EPAS1/Hif2α), aryl hydrocarbon receptor nuclear translocator (ARNT/Hif1β), and signal transducer and activator of transcription 1 (STAT1) as potential master regulators driving the SC transcriptional program. Our results highlight the plastic transcriptional landscape of SCs during the progression of spermatogenesis and provide valuable resources to better understand SC function and spermatogenesis and its related disorders, such as male infertility.

Migrations and gradations : reappraising the health profile of immigrants to Canada

New immigrants to Canada typically have a more favourable health profile than the non-immigrant population. This phenomenon, known as the 'healthy immigrant effect', has been attributed to both the socioeconomic advantage (ie. educational attainment, occupational opportunity) of non-refugee immigrants and existing screening protocols that admit only the healthiest of persons to Canada. It has been suggested that this health advantage diminishes as the time of residence in Canada increases, due in part to the adoption of health-risk behaviours such as alcohol and cigarette use, an increase in excess body weight, and declining rates of physical activity. However, the majority of health research concerning immigrants to Canada has been limited to cross-sectional studies (Dunn & Dyck, 2000; Newbold & Danforth, 2003), which may mask an immigrant-specific cohort effect. Furthermore, the practice of aggregating foreign-bom persons by geographical regions or treating all immigrants as a homogeneous group may also obfuscate intra-immigrant differences in health. Accordingly, this study uses the Canadian National Population Health Surveys (NPHS) and data from the United Nations Development Program (UNDP) to prospectively evaluate factors that predict health status among immigrants to Canada. Each immigrant in the NPHS was linked to the UNDP Human Development Index of their country of birth, which uses a combined measure of health, education, and per capita income of the populace. The six-year change in health function, psychological distress, and self-rated health were considered from a population health perspective (Evans, 1994), using generalized-estimating equations (GEE) to examine the compounding effect of past and recent predictors of health. Demographic

Diversity among bacteria causing blotch disease on the commercial mushroom, agaricus bisporus /

A total of 251 bacterial isolates were isolated from blotched mushroom samples obtained from various mushroom farms in Canada. Out of 251 stored isolates, 170 isolates were tested for pathogenicity on Agaricus bisporus through mushroom rapid pitting test with three distinct pathotypes observed: dark brown, brovm and yellow/yellow-brown blotch. Phenotypic analysis of 83 isolates showed two distinct proteinase K resistant peptide profiles. Profile group A isolates exhibited peptides with masses of 45, 18, 16 and 14 kDa and fiirther biochemical tests identified them as Pseudomonasfluorescens III and V. Profile group B isolates lacked the 16-kDa peptide and the blotch causing bacterial isolates of this group was identified as Serratia liquefaciens and Cedecea davisae. Comparative genetic analysis using Amplified Fragment Length Polymorphism (AFLP) on 50 Pseudomonas sp. isolates (Group A) showed that various blotch symptoms were caused by isolates distributed throughout the Pseudomonas sp. clusters with the exception of the Pseudomonas tolaasii group and one non-pathogenic Pseudomonas fluorescens cluster. These results show that seven distinct Pseudomonas sp. genotypes (genetic clusters) have the ability to cause various symptoms of blotch and that AFLP can discriminate blotch causing from non-blotch causing Pseudomonasfluorescens. Therefore, a complex of diverse bacterial organisms causes bacterial blotch disease

Modulation of muscle contraction by a FMRFamide-related peptide

A FMRFamide-like neuropeptide with the sequence "DRNFLRF-NH2" was recently isolated from pericardial organs of crayfish (Mercier et aI., Peptides, 14, 137-143, 1993). This neuropeptide, referred to as "DF2'" has already been shown to elicit cardioexcitation and to enhance synaptic transmission at neuromuscular junctions. Possible effects ofDF2 on muscle were investigated using superficial extensor muscles of the abdomen of the crayfish, Procambarus clar/ai. These muscles are of the tonic type and generate slow contractions that affect posture. DF2, at concentrations of 10-8 M or higher, increased muscle tonus and induced spontaneous, rhythmic contractions. These effects were antagonized by 5 rnM Mn2+ but not by lO-7M tetrodotoxin (TTX). Thus, they represent direct actions on muscle cells (rather than effects on motor neurons) and are likely to involve calcium influx. In contrast, deep abdominal extensor muscles, responsible for rapid swimming movements, and superficial flexor muscles do not generate contractions in response to the peptide. 2 Spontaneous contractions were also induced in the superficial extensor muscles by decreasing the temperature to II-13°C. Such contractions were also TTX-insensitive and they were antagonized by adding calcium channel blockers (Mn2+, Cd2+ or Ni2+) or by removing calcium from the bathing solution. This suggests that the spontaneous contractions depend on an influx of calcium from the extracellular solution. N-type and L-type voltage dependent calcium channel blockers did not reduce the effect of the peptide or the spontaneous contractions suggesting that calcium influx is not through N- or L-type calcium channels.

Mode of action of FMRFamide-like peptide on drosophila body wall muscle conractions

Neuropeptides are the largest group of signalling chemicals that can convey the information from the brain to the cells of all tissues. DPKQDFMRFamide, a member of one of the largest families of neuropeptides, FMRFamide-like peptides, has modulatory effects on nerve-evoked contractions of Drosophila body wall muscles (Hewes et aI.,1998) which are at least in part mediated by the ability of the peptide to enhance neurotransmitter release from the presynaptic terminal (Hewes et aI., 1998, Dunn & Mercier., 2005). However, DPKQDFMRFamide is also able to act directly on Drosophila body wall muscles by inducing contractions which require the influx of extracellular Ca 2+ (Clark et aI., 2008). The present study was aimed at identifying which proteins, including the membrane-bound receptor and second messenger molecules, are involved in mechanisms mediating this myotropic effect of the peptide. DPKQDFMRFamide induced contractions were reduced by 70% and 90%, respectively, in larvae in which FMRFamide G-protein coupled receptor gene (CG2114) was silenced either ubiquitously or specifically in muscle tissue, when compared to the response of the control larvae in which the expression of the same gene was not manipulated. Using an enzyme immunoassay (EIA) method, it was determined that at concentrations of 1 ~M- 0.01 ~M, the peptide failed to increase cAMP and cGMP levels in Drosophila body wall muscles. In addition, the physiological effect of DPKQDFMRFamide at a threshold dose was not potentiated by 3-lsobutyl-1-methylxanthine, a phosphodiesterase inhibitor, nor was the response to 1 ~M peptide blocked or reduced by inhibitors of cAMP-dependent or cGMP-dependent protein kinases. The response to DPKQDFMRFamide was not affected in the mutants of the phosholipase C-~ (PLC~) gene (norpA larvae) or IP3 receptor mutants, which suggested that the PLC-IP3 pathway is not involved in mediat ing the peptide's effects. Alatransgenic flies lacking activity of calcium/calmodul in-dependent protein kinase (CamKII showed an increase in muscle tonus following the application of 1 JlM DPKQDFMRFamide similar to the control larvae. Heat shock treatment potentiated the response to DPKQDFMRFamide in both ala1 and control flies by approximately 150 and 100 % from a non heat-shocked larvae, respectively. Furthermore, a CaMKII inhibitor, KN-93, did not affect the ability of peptide to increase muscle tonus. Thus, al though DPKQDFMRFamide acts through a G-protein coupled FMRFamide receptor, it does not appear to act via cAMP, cGMP, IP3, PLC or CaMKl1. The mechanism through which the FMRFamide receptor acts remains to be determined.

Profile Portrait of Major General Sir Isaac Brock 1769-1812

This work is a copy of a pastel oval portrait of General Brock that is supposedly the only known portrait of Brock to be done in his lifetime. The original was by William Berczy, circa 1808, and is in the possession of Captain M.H.T Mellish, a descendant of one of Brock's sisters. This portrait was completed on canvas.

Academic advising, eh : a profile of undergraduate academic advising at Ontario universities

Despite its importance to postsecondary students' success, there is little known about academic advisement in Canada. Academic advising can be a very intensive and demanding job, yet it is not well understood what duties or student populations of advising make it so. On a practical level, this study sought to learn more about academic advisement in Ontario universities and provide a general overview of who advisors are and what they do. This study also investigated academic advising duties and time allocation for these responsibilities in an attempt to relate theory to practice incorporating Vilfredo Pareto's theoretical underpinnings to confirm or negate the applicability of the Pareto Principle in relationship to time utilization by advisors. Essentially this study sought to discover which students require the greatest advisement time and effort, and how advisors could apply these findings to their work. Academic advising professionals in Ontario universities were asked to complete a researcher-designed electronic survey. Quantitative data from the responses were analyzed to describe generalized features of academic advising at Ontario universities. Discussion and implications for practice will prompt advisors and institutions using the results of this study to measure themselves against a provincial assessment. Advisors' awareness of time allocation to different student groups can help focus attention where new strategies are needed to maximize time and efforts. This study found that caseload and time spent with student populations were proportional. Regular undergraduate students accounted for the greatest amount of caseload and time followed by working with students struggling academically. This study highlights the need for further evaluation, education, and research in academic advising in Canadian higher education.

Canadian Niagara Power Glass Slide - Plan and Profile of Discharge Tunnel

Plan and profile of discharge tunnel along Niagara River. The horizontal scale is 1 inch = 100 feet, the vertical scale is 1 inch = 40 feet. The drawing is dated November 7, 1902.

Profile of levels of the ditch and creek from Lyon Creek Culvert to Gordon’s Bridge

Profile of levels of the ditch and creek from Lyon Creek Culvert to Gordon’s Bridge (1 page, hand drawn), n.d.

Evaluación de dos diferentes técnicas de instrumentación Light Speed y Profile en conductos moderadamente curvos (Un estudio comparativo)

Tesis ( Maestría en Ciencias Odontológicas con Especialidad en Endodoncia) U.A.N.L.

A Profile of Gamblers

This Study Presents Both a Comprehensive Survey Jof the Empirical Literature on Gambling and Our Most Recent Research Based on Data Provided by Both Loto-Quebec and Statistics Canada. in Spite of All the Excitement Surrounding the Subject, the Typical Gambler Emerges with the Relatively Boring Image of a Regular, Relatively Lower Paid Blue Or White Collar Worker, Whose Career Stalled, Who Is Relatively Older and Has More Children Than the Rest of the Population. But He Is Not Criminal and Does Not Spend Recklessly. the Game Gives Him Hope, Type of Hope That No Other Existing Spending Opportunities Can Provide. the Study Also Reveals That People Do Not Tell the Truth About Their Spendings on Games of Chance.

Harsanyi’s Social Aggregation Theorem : A Multi-Profile Approach with Variable-Population Extensions

This paper provides new versions of Harsanyi’s social aggregation theorem that are formulated in terms of prospects rather than lotteries. Strengthening an earlier result, fixed-population ex-ante utilitarianism is characterized in a multi-profile setting with fixed probabilities. In addition, we extend the social aggregation theorem to social-evaluation problems under uncertainty with a variable population and generalize our approach to uncertain alternatives, which consist of compound vectors of probability distributions and prospects.

Anonymous Single-Profile Welfarism

This note reexamines the single-profile approach to social-choice theory. If an alternative is interpreted as a social state of affairs or a history of the world, it can be argued that a multi-profile approach is inappropriate because the information profile is determined by the set of alternatives. However, single-profile approaches are criticized because of the limitations they impose on the possibility of formulating properties such as anonymity. We suggest an alternative definition of anonymity that applies in a single-profile setting and characterize anonymous single-profile welfarism under a richness assumption.