Accessibility of immunoglobulin (Ig) gene segments to V(D)J recombination is highly regulated and is normally only achieved in B cell precursors. We previously showed that ectopic expression of E2A ...or early B cell factor (EBF) with recombination activating gene (RAG) induces rearrangement of IgH and IgL genes in nonlymphoid cells. VkappaI genes throughout the locus were induced to rearrange after transfection with E2A, suggesting that the entire Vkappa locus was accessible. However, here we show that Ig loci are not opened globally but that recombination is localized. Gene families are interspersed in the D(H), Vkappa, and Vlambda loci, and we show that certain families and individual genes undergo high levels of recombination after ectopic expression of E2A or EBF, while other families within the same locus are not induced to rearrange. Furthermore, in some families, induction of germline transcription correlates with the level of induced recombination, while in others there is no correlation, suggesting that recombination is not simply initiated by induction of germline transcription. The induced repertoire seen at 24 hours does not change significantly over time indicating the absence of many secondary rearrangements and also suggesting a direct targeting mechanism. We propose that accessibility occurs in a local manner, and that binding sites for factors facilitating accessibility are therefore likely to be associated with individual gene segments.
This study examined the utility of the Attachment Style Questionnaire (ASQ) in an Italian sample of 487 consecutively admitted psychiatric participants and an independent sample of 605 nonclinical ...participants. Minimum average partial analysis of data from the psychiatric sample supported the hypothesized five-factor structure of the items; furthermore, multiple-group component analysis showed that this fivefactor structure was not an artifact of differences in item distributions. The five-factor structure of the ASQ was largely replicated in the nonclinical sample. Furthermore, in both psychiatric and nonclinical samples, a two-factor higher order structure of the ASQ scales was observed. The higher order factors of Avoidance and Anxious Attachment showed meaningful relations with scales assessing parental bonding, but were not redundant with these scales. Multivariate normal mixture analysis supported the hypothesis that adult attachment patterns, as measured by the ASQ, are best considered as dimensional constructs.
Immunoglobulin (Ig) and T cell receptor (TCR) genes are assembled during lymphocyte maturation through site-specific V(D)J recombination events. Here we show that E2A proteins act in concert with ...RAG1 and RAG2 to activate Ig Vκ1J but not Igλ VλIII–Jλ1 rearrangement in an embryonic kidney cell line. In contrast, EBF, but not E2A, promotes VλIII–Jλ1 recombination. Either E2A or EBF activate IgH D
H4J recombination but not V(D)J rearrangement. The Ig coding joints are diverse, contain nucleotide deletions, and lack N nucleotide additions. Igκ VJ recombination requires the presence of the E2A transactivation domains. These observations indicate that in nonlymphoid cells a diverse Ig repertoire can be generated by the mere expression of the V(D)J recombinase and a transcriptional regulator.
Intraportal islet transplantation has shown initial promise for the treatment of type 1 diabetes. However, the portal vein site is associated with complications such as thrombosis and hepatic ...steatosis, leading to transplant failure. The aims of this study were to (1) test the feasibility of an alternative islet transplantation method that utilises a FDA-approved gelatin sponge as a novel islet carrier and (2) assess if exogenous addition of nerve growth factor (NGF) has any additional beneficial effects on graft performance in diabetic mice. Mice were rendered diabetic by a single intraperitoneal injection of streptozotocin. Five hundred syngeneic islets were seeded onto a Gelitaspon((R)) disc in the presence or absence of NGF, and placed into a silicone chamber surrounding the femoral neurovascular pedicle. Islet function was assessed by weekly monitoring of blood glucose levels and an intraperitoneal glucose tolerance test performed at the end of the study. Chambers were harvested for further histological analysis. Four of five mice transplanted with islets seeded onto Gelitaspon with NGF showed a significant reduction in blood glucose levels by 4 weeks after transplantation, and demonstrated a response similar to non-diabetic mice when tested with an intraperitoneal glucose tolerance test. Chamber tissue from this group contained islets with insulin-producing beta cells adjacent to the vascular pedicle. Islets seeded onto Gelitaspon with NGF and sited on femoral vessels using a tissue-engineering chamber offer an alternative method for islet transplantation in diabetic mice. This may have potential as a method for clinical islet transplantation.
Although insecure attachment has been associated with a range of variables linked with problematic adjustment to chronic pain, the causal direction of these relationships remains unclear. Adult ...attachment style is, theoretically, developmentally antecedent to cognitions, emotions and behaviours (and might therefore be expected to contribute to maladjustment). It can also be argued, however, that the experience of chronic pain increases attachment insecurity. This project examined this issue by determining associations between adult attachment characteristics, collected prior to an acute (coldpressor) pain experience, and a range of emotional, cognitive, pain tolerance, intensity and threshold variables collected during and after the coldpressor task. A convenience sample of 58 participants with no history of chronic pain was recruited. Results demonstrated that attachment anxiety was associated with lower pain thresholds; more stress, depression, and catastrophizing; diminished perceptions of control over pain; and diminished ability to decrease pain. Conversely, secure attachment was linked with lower levels of depression and catastrophizing, and more control over pain. Of particular interest were findings that attachment style moderated the effects of pain intensity on the tendency to catastrophize, such that insecurely attached individuals were more likely to catastrophize when reporting high pain intensity. This is the first study to link attachment with perceptions of pain in a pain-free sample. These findings cast anxious attachment as a vulnerability factor for chronic pain following acute episodes of pain, while secure attachment may provide more resilience.
The aim of this paper is to examine some of the factors that facilitate and hinder interagency collaboration between child protection services and mental health services in cases where there is a ...parent with a mental illness and there are protection concerns for the child(ren). The paper reports on agency practices, worker attitudes and experiences, and barriers to effective collaboration.
A self-administered, cross-sectional survey was developed and distributed via direct mail or via line supervisors to workers in statutory child protection services, adult mental health services, child and youth mental health services, and Suspected Child Abuse and Neglect (SCAN) Teams. There were 232 completed questionnaires returned, with an overall response rate of 21%. Thirty-eight percent of respondents were statutory child protection workers, 39% were adult mental health workers, 16% were child and youth mental health workers, and 4% were SCAN Team medical officers (with 3% missing data).
Analysis revealed that workers were engaging in a moderate amount of interagency contact, but that they were unhappy with the support provided by their agency. Principle components analysis and multivariate analysis of variance (MANOVA) on items assessing attitudes toward other workers identified four factors, which differed in rates of endorsement: inadequate training, positive regard for child protection workers, positive regard for mental health workers, and mutual mistrust (from highest to lowest level of endorsement). The same procedure identified the relative endorsement of five factors extracted from items about potential barriers: inadequate resources, confidentiality, gaps in interagency processes, unrealistic expectations, and professional knowledge domains and boundaries.
Mental health and child protection professionals believe that collaborative practice is necessary; however, their efforts are hindered by a lack of supportive structures and practices at the organizational level.
Le but de cet article est d’examiner quelques uns des facteurs qui facilitent ou génent la collaboration interadministrative entre les services de protection infantile et les services de santé mentale dans des cas où il existe un parent malade mental et la nécessité de protection à l’égard d’enfants. L’article décrit les pratiques des services, les comportements et les expériences des personnels, ainsi que les obstacles à une collaboration effective.
Une étude représentative auto-gérée a été mise en route et distribuée par courrier direct ou par des superviseurs en ligne à des travailleurs de services spécialisés en protection infantile, des services de santé mentale adulte, des services de santé mentale pour enfants et adolescents, et des équipes spécialisées dans les suspicions de maltraitance et de négligence grave à l’égard d’enfants. 232 questionnaires remplis ont été obtenus, avec un taux global de réponses de 21%. Trente-huit pour cent des répondants étaient des travailleurs spécialisés en protection infantile, 39% des travailleurs en santé mentale adulte, 16% en santé mentale pour enfants et adolescents, 4% des médecins d’equipes spécialisées dans les suspicions de maltraitance ou de négligence grave à l’égard d’enfants (3% d’observations manquantes).
L’analyse a montré que les travailleurs avaient un niveau modéré de contacts interadministration mais qu’ils étaient mécontents de l’aide fournie par leur propre administration. L’analyse des composants et le MANOVA (analyse multivariée de variance) sur les thèmes témoignant des attitudes à l’égard des autres travailleurs ont mis en évidence quatre facteurs différents d’appréciation: formation inadéquate, reconnaissance positive à l’égard des travailleurs en protection infantile, reconnaissance positive à l’égard des travailleurs en santé mentale, méfiance mutuelle (en allant du plus haut au plus bas niveau d’appréciation). La même procédure a montré le niveau relatif d’appréciation sur cinq points portant sur les obstacles potentiels: des moyens inadéquats, la confidentialité, des dysfonctionnements interadministration, des attentes irréalistes, les domaines et les limites de connaissance professionnelle.
Les professionnels en santé mentale et en protection infantile croient qu’une collaboration est nécessaire; cependant leurs efforts sont contrariés par un manque de structures d’aide et les pratiques au niveau organisationnel.
Spanish-language abstract not available at the time of publication.
HLA-B57, as well as cytotoxic T-lymphocyte (CTL) responses restricted by this allele, have been strongly associated with long-term non-progressive chronic HIV-1 infection. However, their impact on ...viral replication during acute HIV-1 infection is not known.
Clinical and immunological parameters during acute and early HIV-1 infection in individuals expressing HLA-B57 were assessed. HIV-1-specific T-cell responses were determined by peptide-specific interferon-gamma production measured using Elispot assay and flow-based intracellular cytokine quantification.
Individuals expressing HLA-B57 presented significantly less frequently with symptomatic acute HIV-1 infection (4/116, 3.4%) than expected from the frequency of chronically infected individuals expressing this allele (43/446, 9.6%; P < 0.05). During acute infection, virus-specific CD8 T-cell responses were dominated by HLA-B57-restricted responses, with significantly broader (P < 0.02) and stronger (P < 0.03) responses restricted by HLA-B57 than restricted by all other co-expressed HLA class I alleles combined. Six out of nine individuals expressing HLA-B57 controlled HIV-1 viremia in the absence of therapy at levels < 5000 copies/ml (median, 515 copies/ml) during up to 29 months following acute infection.
These data demonstrate that host genetic factors can influence the clinical manifestations of acute HIV-1 infection and provide a functional link between HLA-B57 and viral immune control.
This research program focused on perceptions of the appraisals and emotions involved in hurtful events in couple relationships. Study 1 tested the broad proposition that hurt feelings are elicited by ...relational transgressions that generally imply relational devaluation and that evoke a sense of personal injury by threatening positive mental models of self and/or others. Participants (N= 224) provided retrospective accounts of an experience of being hurt by a romantic partner. These accounts, together with expert judges’ ratings, showed that most hurtful events involved relational transgressions that signal both relational devaluation and threat to positive mental models; however, relational devaluation was relatively unimportant in explaining the hurt associated with partners’ distrust. A sense of injury emerged as the dominant theme in open‐ended accounts of emotional reactions; however, other negative emotions also featured and were related to the type of event reported. The emotion terms generated in Study 1 were used as stimuli in a word‐sorting task (Study 2). This study confirmed that many of the terms were perceived specifically as injury related, and shed further light on the link between appraisals and emotions. Theoretical and practical implications of the findings are discussed.
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