A new polycythaemia vera-associated SOCS3 SH2 mutant (SOCS3(F136L)) cannot regulate erythropoietin responses

Recently several different JAK2 exon12 mutations have been identified in V617F negative polycythaemia vera (PV) or idiopathic erythrocytosis (IE) patients. The patients present with erythrocytosis, ligand-independent cell growth and low serum erythropoietin (EPO) levels. Within this group, a deletion of amino acids 542-543 (N542-E543del) of JAK2 is most prevalent. We have previously shown that in the presence of JAK2(V617F), suppressor of cytokine signalling 3 (SOCS3) is unable to negatively regulate EPO signalling and proliferation of V617F-expressing cells. Here we report a PV patient heterozygous for the somatic JAK2(N542-E543del) mutation and a previously unreported germline mutation within the SH2 domain of SOCS3 (F136L). Interestingly, the SOCS3(F136L) mutation was detected in a Japanese myeloproliferative disorder patient cohort at double the frequency of healthy controls. Cells expressing SOCS3(F136L) had markedly elevated EPO-induced proliferation and extended EPO-induced JAK2 phosphorylation. Additionally, compared to wild-type SOCS3, mutant SOCS3 had an extended half-life in the presence of JAK2 and JAK2(N542-E543del). Our findings suggest that this loss-of-function SOCS3 mutation may have contributed to disease onset by causing deregulated JAK2 signalling in the presence of a constitutively active JAK2(N542-E543del) mutant.

Identifying families with multiple problems: Possible responses from child and family social work to current policy developments

In the development of family policy under New Labour there has been a growing tendency to identify groups who are likely to be high in lifetime costs to the state. Investment in such groups is seen as crucial. Whilst the economic case for current investment is compelling, idenitiying one of these groups, ‘families with multiple problems’ raises complex research problems and ethical issues. Reseach indicates that families with multiple problems may be identified on the caseloads of child and family social worker and there are claims that key events such as the registration of a child on the child protection register may indicate such multiple problems. This offers new opportunities for child and family social work to embrace less incident based ways of working in favour of longer term provision of services to address longer term risks.

A healthy settings framework: an evaluation and comparison of midwives' responses to addressing domestic violence

Objectives: to compare and contrast how midwives working in either hospital- or community-based settings address domestic violence by evaluating their views on: prevalence of domestic violence; their role in addressing domestic violence; the acceptability of routine enquiry; and barriers encountered in asking clients questions about violence and abuse in pregnancy. Design: a postal survey questionnaire. Setting: Northern Ireland. Study population: 983 hospital and community midwives. Findings: overall, 488 midwives returned a completed questionnaire; a 57% response rate. Comparisons were made using descriptive, inferential statistics and cross-tabulation. Although there were significant differences between hospital- and community-based midwives in relation to domestic violence, both groups of midwives tended to underestimate its prevalence. Key conclusions: the findings suggest that midwives per se identify and respond to a fraction of the cases of domestic abuse in pregnancy, due to lack of confidence, education and training. This reinforces the need for both hospital and community midwives to gain further confidence and an understanding of the many psychosocial factors that surround domestic violence. Implications for practice: healthy settings theory can be used effectively to identify good practice with women who experience domestic violence. Effective investment for health care requires the gaps between hospital- and community-based practice to be bridged, and for work to be integrated.

The Responses of States to the Comments of the CEDAW Committee on Domestic Violence

This article examines the question of how states have responded to the comments of the United Nations Committee on the Elimination of Discrimination against Women (CEDAW Committee) on the issue of domestic violence, through an analysis of 11 Western European States. It is argued that the majority of the states surveyed are complying with only some of the recommendations of the Committee in relation to domestic violence. This finding serves to highlight the fact that there are certainly major difficulties regarding the implementation of human rights law. This article focuses on the Concluding Observations made by the CEDAW Committee on the reports submitted by the Member States, and problems surrounding these Concluding Observations and the work of the Committee are also examined.

Echinostoma caproni: Differential tegumental responses to growth in compatible and less compatible hosts

The topography of the tegument of Echinostoma caproni adults collected from high (mice) and low (rats) compatible hosts was compared by SEM. In the oral (OS) and the ventral sucker (VS) areas, a worm age-host species interaction was found with regard to the density of spines. There was a decrease in the density of spines in the adults collected from mice, whereas an increase occurred in the OS area in worms from rats over time. The tegumentary spines in adults from mice became larger and blunter. Some spines from the VS area in adults from mice at 4 wpi were multipointed. The spines of adults from rats were sharper, not covered by the tegument and no multipointed spines were observed. We detected a greater level of actin gene expression in the adults collected from rats. These facts suggest that the low compatible host induces an increased turnover of tegumentary spines. (C) 2010 Elsevier Inc. All rights reserved.

Aggressive responses to broadband trills are related to subsequent pairing success in nightingales

In sexually selected signals, distinct components often have specific signal value in mate choice or male-male competition. In songbirds, structural song traits such as trills, that is, a series of repetitive notes, can be important in female choice. However, little is known about their signal value in male-male interactions. Here, we investigated the hypothesis that males assess the competitive abilities of rivals based on the use and performance of rapid broadband trills produced within songs. Using a 2-speaker playback experiment, we exposed territorial male nightingales, Luscinia megarhynchos, that differed in their subsequent pairing success, to a simulated vocal interaction between 2 unfamiliar rivals. The singing of the 2 simulated rivals differed in the number of songs containing rapid broadband trills. Subjects responded significantly more strongly to the loudspeaker that broadcast songs containing such trills than to the loudspeaker that broadcast exclusively songs without such trills. Moreover, responses also depended on the fine structure of trills. Males that became paired later in the season significantly increased their response intensity with increasing trill performance, whereas males that remained unpaired responded in the opposite way and decreased their response intensity with increasing trill performance. These results indicate that rapid broadband trills are a signal of aggression and that the nature of the response in vocal interactions reflects aspects of the challenged male's fitness. © The Author 2008. Published by Oxford University Press on behalf of the International Society for Behavioral Ecology. All rights reserved.


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Responses of calves to acute stress: Individual consistency and relations between behavioral and physiological measures

The present study examined the consistency over time of individual differences in behavioral and physiological responsiveness of calves to intuitively alarming test situations as well as the relationships between behavioral and physiological measures. Twenty Holstein Friesian heifer calves were individually subjected to the same series of two behavioral and two hypothalamo-pituitary-adrenocortical (HPA) axis reactivity tests at 3, 13 and 26 weeks of age. Novel environment (open field, OF) and novel object (NO) tests involved measurement of behavioral, plasma cortisol and heart rate responses. Plasma ACTH and/or cortisol response profiles were determined after administration of exogenous CRH and ACTH, respectively, in the HPA axis reactivity tests. Principal component analysis (PCA) was used to condense correlated measures within ages into principal components reflecting independent dimensions underlying the calves' reactivity. Cortisol responses to the OF and NO tests were positively associated with the latency to contact and negatively related to the time spent in contact with the NO. Individual differences in scores of a principal component summarizing this pattern of inter-correlations, as well as differences in separate measures of adrenocortical and behavioral reactivity in the OF and NO tests proved highly consistent over time. The cardiac response to confinement in a start box prior to the OF test was positively associated with the cortisol responses to the OF and NO tests at 26 weeks of age. HPA axis reactivity to ACTH or CRH was unrelated to adrenocortical and behavioral responses to novelty. These findings strongly suggest that the responsiveness of calves was mediated by stable individual characteristics. Correlated adrenocortical and behavioral responses to novelty may reflect underlying fearfulness, defining the individual's susceptibility to the elicitation of fear. Other independent characteristics mediating reactivity may include activity or coping style (related to locomotion) and underlying sociality (associated with vocalization). (c) 2005 Elsevier Inc. All rights reserved.

Repertoire of HLA-DR1-restricted CD4 T cell responses to capsular Caf1 antigen of Y. pestis HLA-transgenic mice

Yersinia pestis is the causative agent of plague, a rapidly fatal infectious disease that has not been eradicated worldwide. The capsular Caf1 protein of Y. pestis is a protective antigen under development as a recombinant vaccine. However, little is known about the specificity of human T cell responses for Caf1. We characterized CD4 T cell epitopes of Caf1 in 'humanized'-HLA-DR1 transgenic mice lacking endogenous MHC class II molecules. Mice were immunized with Caf1 or each of a complete set of overlapping synthetic peptides, and CD4 T cell immunity was measured with respect to proliferative and IFNgamma T cell responses and recognition by a panel of T cell hybridomas, as well as direct determination of binding affinities of Caf1 peptides to purified HLA-DR molecules. Although a number of DR1-restricted epitopes were identified following Caf1 immunization, the response was biased towards a single immunodominant epitope near the C-terminus of Caf1. In addition, potential promiscuous epitopes, including the immunodominant epitope, were identified by their ability to bind multiple common HLA alleles, with implications for the generation of multivalent vaccines against plague for use in humans.

Interactions between invasive and native crustaceans: differential functional responses of intraguild predators towards juvenile hetero-specifics

Intraguild predation (IGP) between invasive and native species can lead to species exclusions or co-existence, dependent on the direction and strength of the interaction. Recently, derivation of 'functional responses' has been identified as a means of comparing the community impacts of invasive and native species. Here, we employ a novel use of this functional response methodology to evaluate any IGP asymmetries between the invasive Ponto-Caspian amphipod Echinogammarus ischnus and the North American native Gammarus fasciatus. The direction and magnitude of intraguild predation of adult males on hetero-specific adult females has previously been shown to reverse across a water conductivity gradient. This partially explains field patterns, but does not predict the co-existence of the two species observed in many habitats and locations. Here, we compared intraguild predation by both species on each other's juveniles in high- and low- conductivity water. G. fasciatus has a higher type II functional response towards E. ischnus juveniles compared to the reciprocal interaction. Conductivity did not influence the predation rate on juveniles of either E. ischnus or G. fasciatus. Thus, the male/female IGP advantage to the native G. fasciatus in low conductivity water is compounded by a juvenile IGP asymmetry, which also counteracts the male/female IGP advantage to E. ischnus in high conductivity waters, helping to explain field patterns of exclusion and co-existence. Thus, complex asymmetries in mutual IGP associated with inherent species differences, environmental modulation, and life-history effects can help us understand and predict the population and community level outcomes of species invasions.