284 resultados para Sexual signalling hypothesis


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The Irish case provides a particularly appropriate test of the increasing merit selection hypothesis deriving from the liberal theory of industrialization. This is so not only because the lateness and speed of economic change allows us to capture such change through a set of national surveys conducted in the past three decades, but also because such change was based on a sustained policy of increased openness to international competitive forces. The functional requirements of the economy and a rapid increase in the supply of those with higher educational qualifications provided an ideal context in which to observe the movement from ascription to achievement predicted by the liberal theory. However, while changes in the class structure and a rapid expansion of educational opportunity had significant consequences in terms of absolute mobility, there was no evidence of a significant shift towards meritocratic principles. At the same time as the service class increased their advantage over other classes in the pursuit of educational qualifications, the impact of educational qualifications on class destination diminished. Controlling for education, we find that the impact of class origin effects is substantial and shows little sign of diminishing over time. In our conclusion we discuss the implications of our findings in the context of the recent debate on meritocracy.

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The purpose of this paper is to examine the manner in which beliefs relating to sense of control and perceived social support mediate the impact of objective circumstances on psychological distress. In particular it focuses on the nature of the interaction between such variables. The results provide no evidence favouring the displacement hypothesis whereby the benefits of social support involve costs in terms of independence. Consistent support, however, is found for the functional substitution hypothesis. The conclusion is unaffected by the introduction of distinctions relating to types of support and types of power.

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It is now widely accepted that intercellular communication can cause significant variations in cellular responses to genotoxic stress. The radiation-induced bystander effect is a prime example of this effect, where cells shielded from radiation exposure see a significant reduction in survival when cultured with irradiated cells. However, there is a lack of robust, quantitative models of this effect which are widely applicable. In this work, we present a novel mathematical model of radiation-induced intercellular signalling which incorporates signal production and response kinetics together with the effects of direct irradiation, and test it against published data sets, including modulated field exposures. This model suggests that these so-called "bystander" effects play a significant role in determining cellular survival, even in directly irradiated populations, meaning that the inclusion of intercellular communication may be essential to produce robust models of radio-biological outcomes in clinically relevant in vivo situations.

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Rationale: Smooth muscle cells (SMCs) are a key component of tissue-engineered vessels. However, the sources by which they can be isolated are limited.

Objective: We hypothesized that a large number of SMCs could be obtained by direct reprogramming of fibroblasts, that is, direct differentiation of specific cell lineages before the cells reaching the pluripotent state.

Methods and Results: We designed a combined protocol of reprogramming and differentiation of human neonatal lung fibroblasts. Four reprogramming factors (OCT4, SOX2, KLF4, and cMYC) were overexpressed in fibroblasts under reprogramming conditions for 4 days with cells defined as partially-induced pluripotent stem (PiPS) cells. PiPS cells did not form tumors in vivo after subcutaneous transplantation in severe combined immunodeficiency mice and differentiated into SMCs when seeded on collagen IV and maintained in differentiation media. PiPS-SMCs expressed a panel of SMC markers at mRNA and protein levels. Furthermore, the gene dickkopf 3 was found to be involved in the mechanism of PiPS-SMC differentiation. It was revealed that dickkopf 3 transcriptionally regulated SM22 by potentiation of Wnt signaling and interaction with Kremen1. Finally, PiPS-SMCs repopulated decellularized vessel grafts and ultimately gave rise to functional tissue-engineered vessels when combined with previously established PiPS-endothelial cells, leading to increased survival of severe combined immunodeficiency mice after transplantation of the vessel as a vascular graft.

Conclusions: We developed a protocol to generate SMCs from PiPS cells through a dickkopf 3 signaling pathway, useful for generating tissue-engineered vessels. These findings provide a new insight into the mechanisms of SMC differentiation with vast therapeutic potential.

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Non-typable Haemophilus influenzae (NTHi) is a common commensal of the human nasopharynx, but causes opportunistic infection when the respiratory tract is compromised by infection or disease. The ability of NTHi to invade epithelial cells has been described, but the underlying molecular mechanisms are poorly characterized. We previously determined that NTHi promotes phosphorylation of the serine-threonine kinase Akt in A549 human lung epithelial cells, and that Akt phosphorylation and NTHi cell invasion are prevented by inhibition of phosphoinositide 3-kinase (PI3K). Because PI3K-Akt signalling is associated with several host cell networks, the purpose of the current study was to identify eukaryotic molecules important for NTHi epithelial invasion. We found that inhibition of Akt activity reduced NTHi internalization; differently, bacterial entry was increased by phospholipase C?1 inhibition but was not affected by protein kinase inhibition. We also found that a5 and ß1 integrins, and the tyrosine kinases focal adhesion kinase and Src, are important for NTHi A549 cell invasion. NTHi internalization was shown to be favoured by activation of Rac1 guanosine triphosphatase (GTPase), together with the guanine nucleotide exchange factor Vav2 and the effector Pak1. Also, Pak1 might be associated with inactivation of the microtubule destabilizing agent Op18/stathmin, to facilitate microtubule polymerization and NTHi entry. Conversely, inhibition of RhoA GTPase and its effector ROCK increased the number of internalized bacteria. Src and Rac1 were found to be important for NTHi-triggered Akt phosphorylation. An increase in host cyclic AMP reduced bacterial entry, which was linked to protein kinase A. These findings suggest that NTHi finely manipulates host signalling molecules to invade respiratory epithelial cells.

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Men and women differ statistically in the relative lengths of their index and ring fingers; and the ratio of these lengths has been used as a biomarker for prenatal testosterone. The ratio has been correlated with a wide range of traits and conditions including prostate cancer, obesity, autism, ADHD, and sexual orientation. In a genome-wide association study of 979 healthy adults, we find that digit ratio is strongly associated with variation upstream of SMOC1 (rs4902759: P = 1.41 × 10(-8)) and a meta-analysis of this and an independent study shows a probability of P = 1.5 × 10(-11). The protein encoded by SMOC1 has recently been shown to play a critical role in limb development; its expression in prostate tissue is dependent on sex hormones, and it has been implicated in the sexually dimorphic development of the gonads. We put forward the hypothesis that SMOC1 provides a link between prenatal hormone exposure and digit ratio.

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Sex steroids contribute to modulate GH secretion in man. However, both the exact locus and mechanism by which their actions are exerted still remain not clearly understood. We undertook a number of studies designed to ascertain: (1) whether or not sudden or chronic changes in circulating gonadal steroids may affect GH secretion in normal adults; and (2) the reason(s) for gender-related dimorphic pattern of GH release. The pituitary reserve of GH, as evaluated by means of a GHRH challenge, was similar in women with anorexia nervosa and in normally menstruating women. Estrogenic receptor blockade with tamoxifen (TMX) did not significantly change GHRH-induced GH response in these normal women. Therefore, acute or chronic hypoestrogenism apparently had no important effects at level of somatotrophs. In another group of normal women we tested the possibility that changes in circulating estrogens might induce changes in the hypothalamic-somatotroph rhythm (HSR). GHRH challenges were performed throughout a menstrual cycle, and again after having achieved functional ovarian blockade with a GnRH agonist treatment. Short-term ovarian blockade did not significantly affect the parameters of GH response to GHRH, although it was accompanied by an increase in the number of women ina refractory HSR phase at testing. This suggested a low potentiating effect on the basic pattern of somatostatin (SS) release occurring as a consequence of the decrease in circulating estrogens. In normal men, neither the GH response to GHRH nor the HSR were affected by functional testicular blockade (after GnRH agonist treatment). However, the administration of testosterone enanthate (250 mg) to another group of men increased both the GHRH-induced GH release and the number of subjects in a spontaneous secretory HSR phase at testing; these were reversed by estrogenic receptor blockade with TMS. In another group of normal men, the fraction of GH secreted in pulses (FGHP) during a nocturnal sampling period was significantly decreased by testicular blockade. Other parameters of GH secretion, such as the number of GH pulses and their mean amplitude (A), and the mean plasma GH concentration (MCGH), showed a slight, although not significant, decrease following the lack of androgens. The administration of testosterone enanthate (500 mg) reversed these parameters to values similar to those in the basal study. Interestingly, when tamoxifen was given after testosterone enanthate, A, MCGH and FGHP increased to values significantly higher than in any other experimental condition in that study. In all, these data suggest that 17ß-estradiol may participate in GH modulation by inhibiting the hypothalamic release of somatostatin, while testosterone stimulates it. The results obtained after estrogenic receptor blockade appear to indicate that the effect of testosterone in such a modulation is dependent on its aromatization to 17ß-estradiol. The differential levels of this steroid in both sexes might account for the sexual dimorphic pattern of GH secretion. From other data in the literature, obtained in rats, and our preliminary data in children with constitutional delay of growth and puberty, it is tempting to speculate that the effect of 17ß-estradiol may be exerted by modifying the functional activity of a-2 adrenergic pathways involved in the negative modulation of SS release.

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2013 marks 10 years since the Sexual Offences Act 2003 was passed. That Act made significant changes to the law of rape which appear now to have made very little difference to reporting, prosecution or conviction rates. This article argues that the Act has failed against its own measures because it remains enmeshed within a conceptual framework of sexual indifference in which woman continues to be constructed as man’s (defective) other. This construction both constricts the frame in which women’s sexuality can be thought and distorts the harm of rape for women. It also continues woman’s historic alienation from her own nature and denies her entitlement to a becoming in line with her own sexuate identity. Using Luce Irigaray’s critical and constructive frameworks, the article seeks to imagine how law might ‘cognize’ sexual difference and thus take the preliminary steps to a juridical environment in which women can more adequately understand and articulate the harm of rape.

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Objective: This paper uses data provided by the Police Service for Northern Ireland (PSNI) to compare the characteristics and outcomes of reported sexual offences involving child and adult victims and explore the factors associated with case outcomes.
Method: PSNI provided data on 8,789 sexual offences recorded between April 2001 and March 2006. Case outcomes were based on whether a case was recorded by police as having sufficient evidence to summons, charge, or caution an offender (detected). Where an offender was summonsed, charged, or cautioned, this is classified as detection with a formal sanction. A case can also be classified as "detected" without a formal sanction. The analysis focused on two key categories of detection without formal sanction: cases in which the police deem there to be sufficient evidence to charge an offender but took no further action because the victim did not wish to prosecute, or because the police or the Public Prosecution Service (PPS) decided that no useful purpose would be served by proceeding.
Results: The analysis confirmed that the characteristics of recorded sexual offences involving adult and child victims vary significantly according to gender, offence type, the timing of report and victim-offender relationship. Almost half of child sex abuse cases are not detected by police and a quarter do not proceed through the criminal justice system because either the victim declines to prosecute or the Police/PPS decide not to proceed. Only one in five child cases involved detection with a formal sanction. Child groups with lower detection with formal sanction rates included children under 5, teenagers, those who do not report when the abuse occurs but disclose at a later date; and those who experience abuse at the hands of peers and adults known to them but not related. The analysis also highlighted variation in formal sanction rates depending on where the offence was reported.
Conclusions: Consideration needs to be given to improving the criminal justice response to specific child groups as well as monitoring detection rates in different police areas in order to address potential practice variation.
Practice implications: Consideration needs to be given to improving the professional response in relation to with particularly lower detection with formal sanction rates. There is also a need to monitor case outcomes to ensure that child victims in different areas receive a similar service.

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This paper describes the key findings of an NSPCC study estimating need, in the UK, for therapeutic services for children who have experienced sexual abuse. This is based upon current estimates of the prevalence and impact of sexual abuse towards children and young people against the availability of therapeutic services in the UK. Data were collected on service location, availability, scope and coverage across England, Wales, Northern Ireland and Scotland. Researchers: (1) mapped 508 services; (2) collected data from 195 services via a structured questionnaire; (3) followed up 21 service managers and 11 service commissioners with a semi-structured interview; and (4) carried out two focus groups with young people. Data were collected on service location, availability, scope and coverage The overall level of specialist provision is low, with less than one service available per 10 000 children and young people in the UK. Calculations of need indicate that 57 156 children across the UK in the last year may have been unable to access a service. Findings from services support the view that need outstrips availability; that referral routes are limited, leaving few options for young people who have been raped or seriously sexually assaulted to directly access support; that significant waiting lists mean services must focus on reactive, rather than preventive, work; and that services are less accessible for certain groups, especially sexually abused teenagers, children with disabilities and those from Black, Asian, Minority Ethnic and Refugee backgrounds. Copyright (c) 2012 John Wiley & Sons, Ltd. Key Practitioner Messages Relevant professionals must be adequately trained to talk to children about sexual abuse and to identify those vulnerable in order to identify need. Expert specialist services are well placed to share learning on early help and identification with broader children's service providers. Active steps need to be taken by commissioners in consultation with young people, voluntary sector and adult sexual violence service providers to meet the shortfall at the level of local authorities.

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Female involvement in sexual offences against children is more common than is generally thought and has serious implications for the long-term emotional and psychological well-being of victims. Drawing on findings from: a comprehensive review of the literature; an overview of relevant literature and legislation; and an electronic survey of Multi-Agency Public Protection Panels; this paper explores the criminal justice response to female sex offending in England, Wales and Northern Ireland. The literature highlights that the way in which professionals identify and respond to child sexual abuse has been shown to be influenced by the gender of the perpetrator. Equally, whilst similar to male sex offending in terms of the intrusiveness and seriousness of the abuse, some aspects of female sex offending can cause particular problems for professionals. The fact that some sexual abuse can be disguised as childcare can make it difficult for professionals to identify this type of abuse whilst high rates of co-offending bring additional difficulties in determining the degree of female involvement and assigning responsibility. The survey findings indicate that risk assessment tools for female sex offenders is a key area requiring development and point towards small inconsistencies in the current practice of risk assessing females in the community. The survey also identifies the lack of treatment programmes for this group of offenders as well as drawing attention to the need for national policies and procedures, staff training and the identification of areas of good practice. Increased discussion and debate about how best to work with this group of sex offenders is also required. Copyright © 2007 John Wiley & Sons, Ltd.