935 resultados para Partner


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We have cloned a fusion partner of the MLL gene at 11q23 and identified it as the gene encoding the human formin-binding protein 17, FBP17. It maps to chromosome 9q34 centromeric to ABL. The gene fusion results from a complex chromosome rearrangement that was resolved by fluorescence in situ hybridization with various probes on chromosomes 9 and 11 as an ins(11;9)(q23;q34)inv(11)(q13q23). The rearrangement resulted in a 5′-MLL/FBP17-3′ fusion mRNA. We retrovirally transduced murine-myeloid progenitor cells with MLL/FBP17 to test its transforming ability. In contrast to MLL/ENL, MLL/ELL and other MLL-fusion genes, MLL/FBP17 did not give a positive readout in a serial replating assay. Therefore, we assume that additional cooperating genetic abnormalities might be needed to establish a full malignant phenotype. FBP17 consists of a C-terminal Src homology 3 domain and an N-terminal region that is homologous to the cell division cycle protein, cdc15, a regulator of the actin cytoskeleton in Schizosaccharomyces pombe. Both domains are separated by a consensus Rho-binding motif that has been identified in different Rho-interaction partners such as Rhotekin and Rhophilin. We evaluated whether FBP17 and members of the Rho family interact in vivo with a yeast two-hybrid assay. None of the various Rho proteins tested, however, interacted with FBP17. We screened a human kidney library and identified a sorting nexin, SNX2, as a protein interaction partner of FBP17. These data provide a link between the epidermal growth factor receptor pathway and an MLL fusion protein.

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E2F is a heterodimeric transcription factor that regulates the expression of genes at the G1/S boundary and is composed of two related but distinct families of proteins, E2F and DP. E2F/DP heterodimers form complexes with the retinoblastoma (Rb) protein, the Rb-related proteins p107 and p130, and cyclins/cdks in a cell cycle-dependent fashion in vivo. E2F is encoded by at least five closely related genes, E2F-1 through -5. Here we report studies of DP-2, the second member of the DP family of genes. Our results indicate that (i) DP-2 encodes at least five distinct mRNAs, (ii) a site of alternative splicing occurs within the 5' untranslated region of DP-2 mRNA, (iii) at least three DP-2-related proteins (of 55, 48, and 43 kDa) are expressed in vivo, (iv) each of these proteins is phosphorylated, and (v) one DP-2 protein (43 kDa) carries a truncated amino terminus. Our data also strongly suggest that the 55-kDa DP-2-related protein is a novel DP-2 isoform that results from alternative splicing. Thus, we conclude that DP-2 encodes a set of structurally, and perhaps functionally, distinct proteins in vivo.

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The myc gene family encodes a group of transcription factors that regulate cell proliferation and differentiation. These genes are widely studied because of their importance as proto-oncogenes. Phylogenetic analyses are described here for 45 Myc protein sequences representing c-, N-, L-, S-, and B-myc genes. A gene duplication early in vertebrate evolution produced the c-myc lineage and another lineage that later gave rise to the N- and L-myc lineages by another gene duplication. Evolutionary divergence in the myc gene family corresponds closely to the known branching order of the major vertebrate groups. The patterns of sequence evolution are described for five separate highly conserved regions, and these analyses show that differential rates of sequence divergence (= mosaic evolution) have occurred among conserved motifs. Further, the closely related dimerization partner protein Max exhibits significantly less sequence variability than Myc. It is suggested that the reduced variability in max stems from natural selection acting to preserve dimerization capability with products of myc and related genes.

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During the last 15 years several laboratories have attempted to generate rabbit monoclonal antibodies, mainly because rabbits recognize antigens and epitopes that are not immunogenic in mice or rats, two species from which monoclonal antibodies are usually generated. Monoclonal antibodies from rabbits could not be generated, however, because a plasmacytoma fusion partner was not available. To obtain a rabbit plasmacytoma cell line that could be used as a fusion partner we generated transgenic rabbits carrying two transgenes, c-myc and v-abl. These rabbits developed plasmacytomas, and we obtained several plasmacytoma cell lines from which we isolated hypoxanthine/aminopterin/thymidine-sensitive clones. One of these clones, when fused with spleen cells of immunized rabbits, produced stable hybridomas that secreted antibodies specific for the immunogen. The hybridomas can be cloned and propagated in nude mice, and they can be frozen without change in their ability to secrete specific monoclonal antibodies. These rabbit-rabbit hybridomas will be useful not only for production of monoclonal antibodies but also for studies of immunoglobulin gene rearrangements and isotype switching.

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Metazoan cyclin C was originally isolated by virtue of its ability to rescue Saccharomyces cerevisiae cells deficient in G1 cyclin function. This suggested that cyclin C might play a role in cell cycle control, but progress toward understanding the function of this cyclin has been hampered by the lack of information on a potential kinase partner. Here we report the identification of a human protein kinase, K35 [cyclin-dependent kinase 8 (CDK8)], that is likely to be a physiological partner of cyclin C. A specific interaction between K35 and cyclin C could be demonstrated after translation of CDKs and cyclins in vitro. Furthermore, cyclin C could be detected in K35 immunoprecipitates prepared from HeLa cells, indicating that the two proteins form a complex also in vivo. The K35-cyclin C complex is structurally related to SRB10-SRB11, a CDK-cyclin pair recently shown to be part of the RNA polymerase II holoenzyme of S. cerevisiae. Hence, we propose that human K35(CDK8)-cyclin C might be functionally associated with the mammalian transcription apparatus, perhaps involved in relaying growth-regulatory signals.

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In Drosophila the response to the hormone ecdysone is mediated in part by Ultraspiracle (USP) and ecdysone receptor (EcR), which are members of the nuclear receptor superfamily. Heterodimers of these proteins bind to ecdysone response elements (EcREs) and ecdysone to modulate transcription. Herein we describe Drosophila hormone receptor 38 (DHR38) and Bombyx hormone receptor 38 (BHR38), two insect homologues of rat nerve growth factor-induced protein B (NGFI-B). Although members of the NGFI-B family are thought to function exclusively as monomers, we show that DHR38 and BHR38 in fact interact strongly with USP and that this interaction is evolutionarily conserved. DHR38 can compete in vitro against EcR for dimerization with USP and consequently disrupt EcR-USP binding to an EcRE. Moreover, transfection experiments in Schneider cells show that DHR38 can affect ecdysone-dependent transcription. This suggests that DHR38 plays a role in the ecdysone response and that more generally NGFI-B type receptors may be able to function as heterodimers with retinoid X receptor type receptors in regulating transcription.

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The present study explores relationships among several established correlates of trauma in women exposed to intimate partner abuse (IPA), including PTSD, depression, and dissociation symptoms as well as alcohol use as well as other trauma-related variables, such as social support and violence exposure. Two analysis methods were utilized: variable-oriented methods, which examine relationships between variables, and person-oriented analysis methods, which examine groupings of participants within a larger sample (N = 233). Results of the variable-oriented analyses indicated positive links among depression, PTSD, dissociation, and alcohol use in women exposed to IPA, as well as positive links between the aforementioned psychological symptoms and exposure to violence. Social support was related to decreased psychological symptoms. Person-oriented analyses indicated the presence of four unique profiles of women within the larger study sample: Profile 1 (n = 21), which was labeled High Dissociation, Low Depression/PTSD; Profile 2 (n = 150), which was labeled Low Symptoms, High Social Support, Profile 3 (n = 41); which was labeled Low Dissociation, High Depression/PTSD; and Profile 4 (n = 22), which was labeled High Symptoms, Low Social Support. This research supports previous findings about the relationships among several variables related to IPA as well as suggests the need for careful consideration of differences among women within the larger context of research, advocacy, and clinical interventions related to IPA.

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Exposure to intimate partner violence (IPV) puts women at risk for severe and chronic physical and mental health consequences, including elevations in IPV-related psychopathology and increased risk for future victimization. Previous research has examined attention as one of the key information processing mechanisms associated with elevated psychopathology and risk for victimization; however, the nature of attentional processing in response to IPV-related information in women exposed to IPV is poorly understood. Therefore, the current study aimed to further understanding of associations between attentional processing, IPV exposure, and related distress using measures of eye movement and subjective interpretations of IPV-related information. A sample of women exposed to IPV (n = 57) viewed sets of negative, positive, and neutral relationship images for 15 s each while having their eye movements monitored and later provided subjective ratings and interpretations of levels of risk and safety in those images. We examined associations of outcome measures with proximal victimization experiences and IPV-related psychopathology (i.e., depression, posttraumatic stress disorder (PTSD), anxiety, and dissociation). Results indicated a bias to attend to negative relationship images relative to positive and neutral images, though this attention bias fluctuated over time and varied as a function of symptomatology such that depression corresponded with increases in attention to negative images over time and PTSD corresponded with decreases in attention to negative images. The general attention bias for negative images appeared to be explained by rumination on and/or difficulty disengaging from negative images, which was related to general elevations in psychopathology as well as exposure to revictimization by different perpetrators. Subjective interpretations and perception of danger cues were related to victimization history and level and type of IPV-related distress. We replicated these procedures with a sample of undergraduate students without IPV histories or related symptomatology (n = 33) and found that the overall attention bias for negative images was not replicated, despite general similarities in patterns of attention over time. Results therefore indicated associations between attentional processing and IPV exposure and related symptomatology. Implications for models of IPV-related psychopathology and attentional processing as well as directions for future study and interventions are discussed.

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Perinatal depression significantly impacts the mother, her partner, the unborn fetus, and the infant/child after delivery. A review of the literature supports the need for preventive intervention methods as research has shown that even with successful treatment, disruptions in attachment, temperament, and cognitive development often remain. Primary care settings are ideal targets for prevention given that they can reach a number of people at low-cost without the stigma associated with seeking help in a mental health facility. This paper purposes a preventive intervention method for perinatal depression that can be implemented in primary care settings in both Western and non-Western countries. The intervention targets two of the primary risk factors for perinatal depression; partner support and relationship quality. The intervention is structured around key target periods in gestational development and during the early weeks after delivery. Suggestions for each target visit are based on prior research that has demonstrated how psychoeducation about the transition to parenthood, as well as increased communication, can positively affect partner support and relationship quality. The ultimate goal of the intervention is not only to prevent perinatal depression but also to improve the mental health and wellbeing of the entire family system.

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The body of research on the relationship functioning of adults with attention deficit hyperactivity disorder (ADHD) is relatively small; the aim of the present study is to advance our understanding of this topic. It has been estimated that three to ten percent of children and one to five percent of adults have impairing symptoms of ADHD, which is a total of 4 million children and 4-5 million adults in the U.S. (Wender, 2000). A recent prevalence study found that approximately 4.4% of adults in the U.S. meet the criteria for a diagnosis of ADHD (Kessler et al., 2006). Children with ADHD show innate temperamental characteristics, usually inattentiveness, distractibility, impulsivity, restlessness, demandingness, hyperreactivity, low tolerance for frustration, temperoutbursts, bossiness and stubbornness, and mood lability, along with an innate proclivity for academic underachievement. It has been estimated that one- to two-thirds of children with ADHD have symptoms that continue into adulthood, and for 40-50% of these adults, these symptoms are serious enough to cause impairment in functioning (Everett & Everett, 1999; Wender, 2000). Research suggests that the majority of cases are transmitted genetically, but some may be due to exposure to environmental toxins such as lead. Consumption of excess sugar or allergies to food may exacerbate or mimic ADHD symptoms in some children, but they are not a cause of ADHD (Wender, 2000). One hypothesized cause of the symptoms associated with ADHD is a deficit in the brain's executive functioning (Barkley & Gordon, 2002). Executive functioning can be conceptualized as the ability to inhibit, organize, and plan behaviors. Barkley and Gordon (2002) define it as the abilityto self-direct and regulate behaviors toward future goals, including social behaviors and goals. Other research suggests that executive functioning consists of inhibition, control of interference, verbal and nonverbal working memory, emotional regulation, attention, verbal fluency, visual scanning, and processing speed. Studies have shown impairments in these areas among adults with ADHD (Barkley & Gordon, 2002; Barkley, Murphy & Kwasnik, 1996; Goldstein, 2002).

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This study analyzes the effect on levels of patient anxiety and depression of a partner joining a cardiac rehabilitation program support group, also taking into account the sex of the patient. The study was undertaken using a two-group comparison design with pre-and post-test measures in non-equivalent groups. The sample comprised patients in the cardiac rehabilitation program (CRP) at the Ramón y Cajal Hospital, Madrid (Spain). Analysis of covariance (ANCOVA) showed direct effects of sex and partner participation in support groups on the anxiety trait. Similarly, interaction effects were observed between the sex variable and partner participation. These results indicate the pertinence of designing separate groups for patients and partners. © 2014 Universidad Complutense de Madrid and Colegio Oficial de Psicólogos de Madrid.

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PURPOSE: We sought to analyze whether the sociodemographic profile of battered women varies according to the level of severity of intimate partner violence (IPV), and to identify possible associations between IPV and different health problems taking into account the severity of these acts. METHODS: A cross-sectional study of 8,974 women (18-70 years) attending primary healthcare centers in Spain (2006-2007) was performed. A compound index was calculated based on frequency, types (physical, psychological, or both), and duration of IPV. Descriptive and multivariate procedures using logistic regression models were fitted. RESULTS: Women affected by low severity IPV and those affected by high severity IPV were found to have a similar sociodemographic profile. However, divorced women (odds ratio [OR], 8.1; 95% confidence interval [CI], 3.2-20.3), those without tangible support (OR, 6.6; 95% CI, 3.3-13.2), and retired women (OR, 2.7; 95% CI, 1.2-6.0) were more likely to report high severity IPV. Women experiencing high severity IPV were also more likely to suffer from poor health than were those who experienced low severity IPV. CONCLUSIONS: The distribution of low and high severity IPV seems to be influenced by the social characteristics of the women involved and may be an important indicator for estimating health effects. This evidence may contribute to the design of more effective interventions.

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Objectives: To analyze whether sociodemographics and social support have a different or similar effect on the likelihood of Intimate Partner Violence in immigrants and natives, and to estimate prevalences and associations between different types of IPV depending on women's birthplace. Methods: Cross-sectional study of 10,048 women (18–70 years) attending primary healthcare in Spain (2006–2007). Outcome: Current Intimate Partner Violence (psychological, physical and both). Sociodemographics and social support were considered first as explicative and later as control variables. Results: Similar Intimate Partner Violence sociodemographic and social support factors were observed among immigrants and natives. However, these associations were stronger among immigrants, except in the case of poor social support (adjusted odds ratio natives 4.36 and adjusted odds ratio immigrants 4.09). When these two groups were compared, immigrants showed a higher likelihood of IPV than natives (adjusted odds ratios 1.58). Conclusion: Immigrant women are in a disadvantaged Intimate Partner Violence situation. It is necessary that interventions take these inequalities into account.

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Background: Despite the existence of ample literature dealing, on the one hand, with the integration of innovations within health systems and team learning, and, on the other hand, with different aspects of the detection and management of intimate partner violence (IPV) within healthcare facilities, research that explores how health innovations that go beyond biomedical issues—such as IPV management—get integrated into health systems, and that focuses on healthcare teams’ learning processes is, to the best of our knowledge, very scarce if not absent. This realist evaluation protocol aims to ascertain: why, how, and under what circumstances primary healthcare teams engage (if at all) in a learning process to integrate IPV management in their practices; and why, how, and under what circumstances team learning processes lead to the development of organizational culture and values regarding IPV management, and the delivery of IPV management services. Methods: This study will be conducted in Spain using a multiple-case study design. Data will be collected from selected cases (primary healthcare teams) through different methods: individual and group interviews, routinely collected statistical data, documentary review, and observation. Cases will be purposively selected in order to enable testing the initial middle-range theory (MRT). After in-depth exploration of a limited number of cases, additional cases will be chosen for their ability to contribute to refining the emerging MRT to explain how primary healthcare learn to integrate intimate partner violence management. Discussion: Evaluations of health sector responses to IPV are scarce, and even fewer focus on why, how, and when the healthcare services integrate IPV management. There is a consensus that healthcare professionals and healthcare teams play a key role in this integration, and that training is important in order to realize changes. However, little is known about team learning of IPV management, both in terms of how to trigger such learning and how team learning is connected with changes in organizational culture and values, and in service delivery. This realist evaluation protocol aims to contribute to this knowledge by conducting this project in a country, Spain, where great endeavours have been made towards the integration of IPV management within the health system.

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The purpose of this study is to estimate the prevalence of lifetime intimate partner violence (IPV) in older women and to analyze its effect on women's health and Healthcare Services utilization. Women aged 55 years and over (1,676) randomly sampled from Primary Healthcare Services around Spain were included. Lifetime IPV prevalence, types, and duration were calculated. Descriptive and multivariate procedures using logistic and multiple lineal regression models were used. Of the women studied, 29.4% experienced IPV with an average duration of 21 years. Regardless of the type of IPV experienced, abused women showed significantly poorer health and higher healthcare services utilization compared to women who had never been abused. The high prevalence detected long standing duration, negative health impact, and high healthcare services utilization, calling attention to a need for increased efforts aimed at addressing IPV in older women.