Specific inhibition of the differentiation of Trypanosoma cruzi

The morphological transformation of Trypanosoma cruzi amastigotes was studied in both mammalian cells and an extracellular differentiation system. Inhibitors of ADP-ribosyl transferase were found to block differentiation in both cases, without affecting proliferation. The inhibitory effect was reversible and was not observed with chemical analogues that do not inhibit ADP-ribosyl transferase. As inhibitors of ADP-ribosyl transferase have recently been shown to block the differentiation of several cell types from vertebrates (Farzaneh, F., R. Zalin, D. Brill, and S. Shall, 1982, Nature (Lond.), 300:362-366; Johnstone, A. P., and G. T. Williams, 1982, Nature (Lond.), 300:368-370), our results suggest that the enzyme is of general importance in eucaryotic differentiation both in multicellular and unicellular organisms. In addition, since the compounds can block T. cruzi differentiation inside mammalian cells, these results suggest that it may be possible to exploit such inhibition in a new and potentially powerful approach to the chemotherapy of several important parasitic diseases

The Spycatcher Saga

The central facts in the unfolding of the Spycatcher saga are relatively well-known. Peter Wright left M.I.5 in 1976 after some twenty years\u27 service in the shadows; his health was bad , his pension derisory , but he had his memories. After retirement he went to live in Tasmania, where (according to Kirby P in the Court of Appeal of New South Wales) he still resides in a place with the idyllic name of Cygnet. Despite the distance Peter Wright remained closely involved in the welter of allegations and denials, which emerged especially after the unmasking of Anthony Blunt as a former double agent in late 1979, about the inner workings of M.I.5 and Soviet penetration of M.I.5. In 1984 a television interview with Mr. Wright concerned in part the suggestion that Sir Roger Hollis, a former Director-General of M.I.5, had been a Soviet agent. In March 1985 Mr. Wright was approached by a representative of Heinemann, the publisher, to write a candid account of his life in the shadows; and the British government, on learning of these plans, sought injunctions in the courts of New South Wales. The contents of Spycatcher, as it became, ranged far beyond the allegations concerning Sir Roger Hollis to encompass allegations about the bugging of diplomatic premises and of diplomatic conferences, about a plot to assassinate President Nasser of Egypt, about attempts to destabilise the Labour government under Mr. Harold Wilson, and about much else. Many of the allegations had appeared in print before Spycatcher emerged, but the status of the author, it was claimed by the Crown, gave them a special ring of authenticity

The antiapoptotic RBM5/LUCA-15/H37 gene and its role in apoptosis and human cancer: research update.

The candidate tumour-suppressor gene, LUCA-15/RBM5/H37, maps to the lung cancer tumour-suppressor locus 3p21.3. The LUCA-15 gene locus encodes at least four alternatively spliced transcripts that have been shown to function as regulators of apoptosis, a fact which may have major significance in tumour regulation. This review highlights recent evidence that further implicates the LUCA-15 locus in the control of apoptosis and cell proliferation, and focuses on the observations that confirm the tumour-suppressor activity of this gene

Inhibition of Human T-Cell Proliferation by mTOR antagonists requires Non-Coding RNA growth-arrest-specific transcript 5 (GAS5)

BACKGROUND: Eosinophils are characteristic participants in allergic inflammation. The intracellular signalling mechanisms involved in the migration of eosinophils to sites of allergic inflammation are poorly understood. Chemotactic responses of eosinophils to platelet-activating factor (PAF), but not eotaxin, have been demonstrated to be dependent upon the activation of phosphoinositide 3-kinase (PI3K) but the specific isoform of PI3K involved has not been identified. OBJECTIVE: To determine the roles of the leukocyte-specific PI3K gamma and PI3K delta isoforms of PI3K in PAF-induced chemotaxis of human eosinophils. METHODS: Chemotactic responses of the EoL-1 eosinophilic cell line and human peripheral blood eosinophils were measured. The effects of a PI3K gamma-selective inhibitor (5-[2,2-difluorobenzo(1,3)dioxol-5-ylmethylene]-thiazolidine-2,4-dione; AS604850) and gene knock-down of PI3K gamma and PI3K delta on chemotactic responses were determined. RESULTS: AS604850 caused a concentration-dependent suppression of chemotactic responses of EoL-1 cells and blood eosinophils to PAF but not eotaxin. Specific siRNAs reduced the expression of PI3K gamma and PI3K delta in EoL-1 cells. Knock-down of PI3K gamma by siRNA resulted in a 75% inhibition of the chemotactic response to PAF but had no effect on the response to eotaxin. Knock-down of endogenous PI3K delta by siRNA resulted in a 38% inhibition of the chemotactic response to PAF but had no effect on the response to eotaxin. CONCLUSION: PI3K gamma plays a major role in the induction of chemotaxis in PAF-stimulated eosinophils, while PI3K delta plays a lesser role. Interventions which reduce the activity The central importance of the serine/threonine protein kinase mTOR (mammalian Target of Rapamycin) in the control of cell growth and proliferation is well established. However, our knowledge both of the upstream pathways controlling mTOR activity and of the downstream events mediating these effects is still seriously incomplete. We report a previously unsuspected role for the nonprotein-coding RNA GAS5 in the inhibition of T-cell proliferation produced by mTOR antagonists such as rapamycin. GAS5 transcripts are up-regulated during growth arrest and after rapamycin treatment, and GAS5 has recently been shown to be necessary and sufficient for normal T-cell growth arrest. Down-regulation of GAS5 using RNA interference protects both leukemic and primary human T cells from the inhibition of proliferation produced by mTOR antagonists. The GAS5 transcript is a member of the 5' terminal oligopyrimidine class of RNAs, which is specifically controlled at the level of translation by the mTOR pathway, and the effects of GAS5 on the cell cycle provide a novel and important link to the control of proliferation. These observations point to a significant advance in our understanding of the mechanism of action of mTOR inhibitors, which is likely to lead to improvements in immunosuppressive and cancer therapy

BCL2L14 (BCL2-like 14 (apoptosis facilitator))

Review on BCL2L14, with data on DNA/RNA, on the protein encoded and where the gene is implicated

Poor sleep quality, antepartum depression and suicidal ideation among pregnant women.

To evaluate the independent and combined associations of maternal self-reported poor sleep quality and antepartum depression with suicidal ideation during the third trimester METHODS: A cross-sectional study was conducted among 1298 pregnant women (between 24 and 28 gestational weeks) attending prenatal clinics in Lima, Peru. Antepartum depression and suicidal ideation were assessed using the Patient Health Questionnaire-9 (PHQ-9). The Pittsburgh Sleep Quality Index (PSQI) questionnaire was used to assess sleep quality. Multivariate logistical regression procedures were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) after adjusting for putative confounders. Approximately, 17% of women were classified as having poor sleep quality (defined using the recommended criteria of PSQI global score of >5 vs. ≤5). Further, the prevalence of antepartum depression and suicidal ideation were 10.3% and 8.5%, respectively in this cohort. After adjusting for confounders including depression, poor sleep quality was associated with a 2.81-fold increased odds of suicidal ideation (OR=2.81; 95% CI 1.78-4.45). When assessed as a continuous variable, each 1-unit increase in the global PSQI score resulted in a 28% increase in odds for suicidal ideation, even after adjusting for depression (OR=1.28; 95% CI 1.15-1.41). The odds of suicidal ideation was particularly high among depressed women with poor sleep quality (OR=13.56 95% CI 7.53-24.41) as compared with women without either risk factor. This cross-sectional study utilized self-reported data. Causality cannot be inferred, and results may not be fully generalizable. Poor sleep quality, even after adjusting for depression, is associated with antepartum suicidal ideation. Our findings support the need to explore sleep-focused interventions for pregnant women

The many positive impacts of participating in outreach activities on postgraduate students

Postgraduate students are excellent role models for school students, where their passion and energy play a vital role in engaging younger students and spreading enthusiasm and excitement about science. However, participating in outreach is not a one way activity for these postgraduate students. Through focus groups we show that the postgraduate students perceive that there are many benefits for themselves. These benefits are identified and discussed. This paper also contrasts the postgraduate with their undergraduate counterpart in terms of their contributions to engagement activities

Prognostic value of lymph node ratio and extramural vascular invasion on survival for patients undergoing curative colon cancer resection

There was no study funding. We are grateful to Tony Rafferty (Tailored Information for the People of Scotland, TIPs) for providing survival data.Peer reviewedPublisher PD

The relationship between sensory sensitivity and autistic traits in the general population.

Individuals with Autism Spectrum Disorders (ASDs) tend to have sensory processing difficulties (Baranek et al. in J Child Psychol Psychiatry 47:591–601, 2006). These difficulties include over- and under-responsiveness to sensory stimuli, and problems modulating sensory input (Ben-Sasson et al. in J Autism Dev Disorders 39:1–11, 2009). As those with ASD exist at the extreme end of a continuum of autistic traits that is also evident in the general population, we investigated the link between ASD and sensory sensitivity in the general population by administering two questionnaires online to 212 adult participants. Results showed a highly significant positive correlation (r = .775, p < .001) between number of autistic traits and the frequency of sensory processing problems. These data suggest a strong link between sensory processing and autistic traits in the general population, which in turn potentially implicates sensory processing problems in social interaction difficulties