Hoxa6 potentiates short-term hemopoietic cell proliferation and extended self-renewal.

Hemopoietic progenitor cells express clustered homeobox (Hox) genes in a pattern characteristic of their lineage and stage of differentiation. In general, HOX expression tends to be higher in more primitive and lower in lineage-committed cells. These trends have led to the hypothesis that self-renewal of hemopoietic stem/progenitor cells is HOX-dependent and that dysregulated HOX expression underlies maintenance of the leukemia-initiating cell. Gene expression profile studies support this hypothesis and specifically highlight the importance of the HOXA cluster in hemopoiesis and leukemogenesis. Within this cluster HOXA6 and HOXA9 are highly expressed in patients with acute myeloid leukemia and form part of the "Hox code" identified in murine models of this disease. We have examined endogenous expression of Hoxa6 and Hoxa9 in purified primary progenitors as well as four growth factor-dependent cell lines FDCP-Mix, EML, 32Dcl3, and Ba/F3, representative of early multipotential and later committed precursor cells respectively. Hoxa6 was consistently higher expressed than Hoxa9, preferentially expressed in primitive cells and was both growth-factor and cell-cycle regulated. Enforced overexpression of HOXA6 or HOXA9 in FDCP-Mix resulted in increased proliferation and colony formation but had negligible effect on differentiation. In both FDCP-Mix and the more committed Ba/F3 precursor cells overexpression of HOXA6 potentiated factor-independent proliferation. These findings demonstrate that Hoxa6 is directly involved in fundamental processes of hemopoietic progenitor cell development.

Is shyness context specific? Relation between shyness and online self-disclosure with and without a live webcam in young adults

The Internet provides a new tool to investigate old questions in experimental social psychology regarding Person x Context interaction. We examined the interaction of self-reported shyness and context on computer-mediated communication measures. Sixty female undergraduates unfamiliar were paired in dyads and engaged in a 10 min free chat conversation on the Internet with and without a live webcam. Free chat conversations were archived, transcripts were objectively coded for communication variables, and a linear mixed model used for data analysis of dyadic interaction was performed on each communication measure. As predicted, increases in self-reported shyness were significantly related to decreases in the number of prompted self-disclosures (after controlling for the number of opportunities to self-disclose) only in the webcam condition. Self-reported shyness was not related to the number of prompted self-disclosures in the no webcam condition, suggesting that shyness was context dependent. The present study appears to be the first to objectively code measures of Internet behaviour in relation to the study of personality in general and shyness in particular. Theoretical and clinical implications for understanding the contextual nature of shyness are discussed. (C) 2006 Elsevier Inc. All rights reserved.

Genetic testing and the relationship between specific and general self-efficacy

The study examined the extent to which variations in health-specific self-efficacy could affect general self-efficacy. In a repeated measures design, 300 participants were administered an efficacy questionnaire, before and after an alleged news report, aimed at increasing or decreasing self-efficacy over genetic-testing decision making. The results found that self-efficacy over testing was significantly reduced after reading the negative news report in those participants who felt personal efficacy over testing decisions was important. Levels of general self-efficacy were also significantly decreased. The findings suggest that being denied control over a specific area of self-efficacy can have a wider impact, with a lack of perceived efficacy over testing decision making adversely impacting on levels of general well-being. The wider implications of this generalization effect and the processes involved in efficacy generalization are discussed.

Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5.

The 5' cap structures of higher eukaryote mRNAs have ribose 2'-O-methylation. Likewise, many viruses that replicate in the cytoplasm of eukaryotes have evolved 2'-O-methyltransferases to autonomously modify their mRNAs. However, a defined biological role for 2'-O-methylation of mRNA remains elusive. Here we show that 2'-O-methylation of viral mRNA was critically involved in subverting the induction of type I interferon. We demonstrate that human and mouse coronavirus mutants lacking 2'-O-methyltransferase activity induced higher expression of type I interferon and were highly sensitive to type I interferon. Notably, the induction of type I interferon by viruses deficient in 2'-O-methyltransferase was dependent on the cytoplasmic RNA sensor Mda5. This link between Mda5-mediated sensing of viral RNA and 2'-O-methylation of mRNA suggests that RNA modifications such as 2'-O-methylation provide a molecular signature for the discrimination of self and non-self mRNA.

Living arrangements, relationship to people in the household and admission to care homes for older people

Objective: to assess the separate contributions of marital status, living arrangements and the presence of children to subsequent admission to a care home.

Design and methods: a longitudinal study derived from the health card registration system and linked to the 2001 Census, comprising 28% of the Northern Ireland population was analysed using Cox regression to assess the likelihood of admission for 51,619 older people in the 6 years following the census. Cohort members’ age, sex, marital and health status and relationship to other household members were analysed.

Results: there were 2,138 care home admissions; a rate of 7.4 admissions per thousand person years. Those living alone had the highest likelihood of admission [hazard ratio (HR) compared with living with partner 1.66 (95% CI 1.48, 1.87)] but there was little difference between the never-married and the previously married. Living with children offered similar protection as living with a partner (HR 0.97; 95% CI 0.81, 1.16). The presence of children reduced admissions especially for married couples (HR 0.67 95% CI 0.54, 0.83; models adjusting for age, gender and health). Women were more likely to be admitted, though there were no gender differences for people living alone or those co-habiting with siblings.

Implications: presence of potential caregivers within the home, rather than those living elsewhere, is a major factor determining admission to care home. Further research should concentrate on the health and needs of these co-residents.

Fasciola hepatica: Comparative effects of host resistance and parasite intra-specific interactions on size and reproductive histology in flukes from rats infected with isolates differing in triclabendazole sensitivity

The efficacies of putative fasciolicides and vaccines against Fasciola hepatica are frequently monitored in clinical and field trials by determination of fluke egg output in host faeces and by worm counts in the host liver at autopsy. Less often used are parameters based on fluke size and histology, yet these can provide important indications of specific effects on the development of particular germ-line or somatic tissues, especially in relation to the timing and profligacy of egg production. In this study. F. hepatica metacercariae of two distinct isolates, the triclabendazole (TCBZ)-sensitive Cullompton isolate and the TCBZ-resistant Oberon isolate, were administered to rats as single-isolate or mixed-isolate infections. At autopsy 16 weeks later individual adult flukes were counted, measured and the reproductive organs were examined histologically. The degree of development of the testis tubules in each fluke was represented by a numerical score, based on the proportion of the histological section profiles occupied by testis tissue. The level of anti-F. hepatica antibody in the serum of each rat was determined by ELISA. It was found that Cullompton flukes were significantly larger than Oberon flukes, and that significantly more Cullompton metacercariae developed to adults than Oberon metacercariae. The Cullompton flukes showed histological evidence of aspermy and spermatogenic arrest, which was reflected in quantitatively reduced testicular development, as compared with the Oberon isolate. In Cullompton flukes, parthenogenetic egg development is implied. The size of Cullompton and Oberon flukes was significantly related to the number of adult flukes recovered, to the number of metacercariae administered, and to the percentage success of infection. The testis development score in both isolates was significantly related to the number of adult flukes recovered but not to the number of metacercariae administered, or to the percentage success of infection. Fluke size was positively related to testis score for both isolates, and a significant negative relationship was found between percentage success of infection and metacercarial dose. The results are interpreted in terms of differing interactions between various numbers of young flukes and host immunity during invasion of and migration in the hepatic parenchyma, and of fluke intra-specific (possibly pheromonal) stimulatory effects in the final stages of development, within the host bile ducts. No significant relationships were found between host antibody levels and fluke size or testis score. False positive serological reactions were found in some rats that had been infected, but found to harbour no flukes at autopsy. Clearly the act of eliminating the flukes involved generation of an immune response. (C) 2011 Elsevier B.V. All rights reserved.