"Not Just One, It's Both of Us": Low-Income Mothers' Perceptions of Structural Family Therapy Delivered in a Semi-rural Community Mental Health Center.

Qualitative methods were used to explore mothers' perceptions of structural family therapy (SFT) delivered in a semi-rural community mental health clinic. In-depth, semi-structured interviews were conducted with sixteen mothers who received SFT after seeking services for their children. Thematic analysis suggests mothers found SFT acceptable and valuable. Mothers reported using SFT strategies to regain parental authority, which they believed improved their ability to manage their child's needs and decreased their own stress. SFT also increased some mothers' receptivity to individual treatment. Mothers identified their low dose of treatment and lack of father involvement as impediments to improvement, raising concerns about intervention sustainability.

Reduced Crossover Interference and Increased ZMM-Independent Recombination in the Absence of Tel1/ATM.

Meiotic recombination involves the repair of double-strand break (DSB) precursors as crossovers (COs) or noncrossovers (NCOs). The proper number and distribution of COs is critical for successful chromosome segregation and formation of viable gametes. In budding yeast the majority of COs occurs through a pathway dependent on the ZMM proteins (Zip2-Zip3-Zip4-Spo16, Msh4-Msh5, Mer3), which form foci at CO-committed sites. Here we show that the DNA-damage-response kinase Tel1/ATM limits ZMM-independent recombination. By whole-genome mapping of recombination products, we find that lack of Tel1 results in higher recombination and reduced CO interference. Yet the number of Zip3 foci in tel1Δ cells is similar to wild type, and these foci show normal interference. Analysis of recombination in a tel1Δ zip3Δ double mutant indicates that COs are less dependent on Zip3 in the absence of Tel1. Together these results reveal that in the absence of Tel1, a significant proportion of COs occurs through a non-ZMM-dependent pathway, contributing to a CO landscape with poor interference. We also see a significant change in the distribution of all detectable recombination products in the absence of Tel1, Sgs1, Zip3, or Msh4, providing evidence for altered DSB distribution. These results support the previous finding that DSB interference depends on Tel1, and further suggest an additional level of DSB interference created through local repression of DSBs around CO-designated sites.

Controlling meiotic recombinational repair - specifying the roles of ZMMs, Sgs1 and Mus81/Mms4 in crossover formation.

Crossovers (COs) play a critical role in ensuring proper alignment and segregation of homologous chromosomes during meiosis. How the cell balances recombination between CO vs. noncrossover (NCO) outcomes is not completely understood. Further lacking is what constrains the extent of DNA repair such that multiple events do not arise from a single double-strand break (DSB). Here, by interpreting signatures that result from recombination genome-wide, we find that synaptonemal complex proteins promote crossing over in distinct ways. Our results suggest that Zip3 (RNF212) promotes biased cutting of the double Holliday-junction (dHJ) intermediate whereas surprisingly Msh4 does not. Moreover, detailed examination of conversion tracts in sgs1 and mms4-md mutants reveal distinct aberrant recombination events involving multiple chromatid invasions. In sgs1 mutants, these multiple invasions are generally multichromatid involving 3-4 chromatids; in mms4-md mutants the multiple invasions preferentially resolve into one or two chromatids. Our analysis suggests that Mus81/Mms4 (Eme1), rather than just being a minor resolvase for COs is crucial for both COs and NCOs in preventing chromosome entanglements by removing 3'- flaps to promote second-end capture. Together our results force a reevaluation of how key recombination enzymes collaborate to specify the outcome of meiotic DNA repair.

Kinetic analysis of synaptonemal complex dynamics during meiosis of yeast Saccharomyces cerevisiae reveals biphasic growth and abortive disassembly.

The synaptonemal complex (SC) is a dynamic structure formed between chromosomes during meiosis which stabilizes and supports many essential meiotic processes such as pairing and recombination. In budding yeast, Zip1 is a functionally conserved element of the SC that is important for synapsis. Here, we directly measure the kinetics of Zip1-GFP assembly and disassembly in live cells of the yeast S. cerevisiae. The imaging of SC assembly in yeast is challenging due to the large number of chromosomes packed into a small nucleus. We employ a zip3Δ mutant in which only a few chromosomes undergo synapsis at any given time, initiating from a single site on each chromosome, thus allowing the assembly and disassembly kinetics of single SCs to be accurately monitored in living cells. SC assembly occurs with both monophasic and biphasic kinetics, in contrast to the strictly monophasic assembly seen in C. elegans. In wild-type cells, once maximal synapsis is achieved, programmed final disassembly rapidly follows, as Zip1 protein is actively degraded. In zip3Δ, this period is extended and final disassembly is prolonged. Besides final disassembly, we found novel disassembly events involving mostly short SCs that disappeared in advance of programmed final disassembly, which we termed "abortive disassembly." Abortive disassembly is distinct from final disassembly in that it occurs when Zip1 protein levels are still high, and exhibits a much slower rate of disassembly, suggesting a different mechanism for removal in the two types of disassembly. We speculate that abortive disassembly events represent defective or stalled SCs, possibly representing SC formation between non-homologs, that is then targeted for dissolution. These results reveal novel aspects of SC assembly and disassembly, potentially providing evidence of additional regulatory pathways controlling not just the assembly, but also the disassembly, of this complex cellular structure.

Case managers' perspectives on what they need to do their job.

OBJECTIVE: The purpose of this brief report is to identify the perceived training needs of case managers working on community support teams in a community mental health center serving a semi-rural/suburban area. METHODS: Semi-structured interviews were conducted with 18 case managers and 3 supervisors to inquire about areas of training need in case management. Interviews were coded and analyzed for common themes regarding training needs and methods of training improvement. RESULTS: Identified training needs called for a hands-on, back-to-basics approach that included education on the symptoms of severe mental illness, co-morbid substance use problems, and methods of engaging consumers. A mentoring model was proposed as a potential vehicle for disseminating knowledge in these domains. CONCLUSIONS: Case managers identify significant training needs that would address their basic understanding of severe mental illness. Programs targeting these needs may result in improved outcomes for case managers and the individuals with psychiatric disabilities they serve.

Quality of life for persons living with schizophrenia: more than just symptoms.

Quality of life is an important outcome for persons living with schizophrenia and for the treatment of schizophrenia. However, studies of quality of life among persons living with schizophrenia have focused primarily on the symptoms experienced by the individual. This study sought to determine the influence of unmet need and social support on the quality of life of individuals with schizophrenia. Thirty-two persons living in the community with schizophrenia or schizoaffective disorder were assessed on quality of life, psychopathology, unmet need and social support. Hierarchical regression analyses indicated that unmet need and social support are important contributors to the quality of life of a person with schizophrenia, even after controlling for symptoms. Implications for schizophrenia treatment are discussed.

Why lower income mothers do not engage with the formal mental health care system: perceived barriers to care.

Lower income mothers who bring their children for mental health services also have high rates of depression and anxiety, yet few seek help. Maternal and child mental health are intimately intertwined; thus, the distress of both is likely to continue if the mother's needs are unaddressed. Because mothers overcome numerous instrumental challenges to help their children, the authors identify potential perceptual barriers to mothers' help seeking. An ethnographic analysis of in-depth qualitative interviews with 127 distressed mothers suggests several critical perceptual factors. For example, mothers attributed their distress to external causes (e.g., poverty, negative life stressors), which they believed individually focused mental health services could not affect. Interviewees also anticipated negative ramifications for seeking care, including being labeled unfit mothers, and thus potentially losing custody of their children. The authors discuss the implications of these and other key themes for engaging lower income mothers and their children.

Weight gain information on the Internet for people who have schizophrenia.

Weight gain and chronic health problems are highly prevalent among people with schizophrenia. Basic information about diet and exercise changes would be very useful to people with schizophrenia as well as the family members and clinicians. Because people increasingly seek information from the World Wide Web, this paper reports on a survey of weight-related information on available web sites. A survey of 21 schizophrenia websites revealed that although fourteen sites (67%) included some information about weight gain and related health problems, more than half of the information was limited to site user-generated comments, and consisted of less than one paragraph of information.

Return to treatment after assessment in a community children's mental health clinic.

Most people who receive mental health assessments do not follow up on needed treatment. The authors examined factors that predicted return for at least one treatment visit among 113 children who presented for treatment at a rural community mental health center, using predictors of return for adults from a previous study. Sixty-four percent of the children, compared with 46 percent of the adults, returned at least once. Time until the first appointment predicted whether patients returned for treatment. The age of the child was the only other variable that predicted initial treatment engagement. The results strongly suggest that community mental health agencies can improve treatment acceptance rates by providing rapid response to requests for treatment.

ReCombine: a suite of programs for detection and analysis of meiotic recombination in whole-genome datasets.

In meiosis, the exchange of DNA between chromosomes by homologous recombination is a critical step that ensures proper chromosome segregation and increases genetic diversity. Products of recombination include reciprocal exchanges, known as crossovers, and non-reciprocal gene conversions or non-crossovers. The mechanisms underlying meiotic recombination remain elusive, largely because of the difficulty of analyzing large numbers of recombination events by traditional genetic methods. These traditional methods are increasingly being superseded by high-throughput techniques capable of surveying meiotic recombination on a genome-wide basis. Next-generation sequencing or microarray hybridization is used to genotype thousands of polymorphic markers in the progeny of hybrid yeast strains. New computational tools are needed to perform this genotyping and to find and analyze recombination events. We have developed a suite of programs, ReCombine, for using short sequence reads from next-generation sequencing experiments to genotype yeast meiotic progeny. Upon genotyping, the program CrossOver, a component of ReCombine, then detects recombination products and classifies them into categories based on the features found at each location and their distribution among the various chromatids. CrossOver is also capable of analyzing segregation data from microarray experiments or other sources. This package of programs is designed to allow even researchers without computational expertise to use high-throughput, whole-genome methods to study the molecular mechanisms of meiotic recombination.

Web-based psychoeducational intervention for persons with schizophrenia and their supporters: one-year outcomes.

OBJECTIVE: This study examined the use of a uniquely designed Web site and home computers to deliver online multifamily psychoeducational therapy to persons with schizophrenia and their informal supports (family and friends). Web site usage and outcome benefits are reported. METHODS: Thirty-one persons with schizophrenia or schizoaffective disorder and 24 support persons were randomly assigned to the online intervention (telehealth) or treatment as usual (usual care) condition. At three, six, and 12 months, interviewer-administered assessments were conducted with participants. Intention-to-treat analyses compared persons with schizophrenia in the two study conditions on severity of positive symptoms and knowledge of schizophrenia. Support persons in the two study conditions were compared on knowledge of schizophrenia. Each participant's usage of the Web site was logged. RESULTS: Persons with schizophrenia in the telehealth condition had a large and significant reduction in positive symptoms (p=.042, d=-.88) and a large and significant increase in knowledge of schizophrenia compared with their counterparts in the usual care condition. Support persons in the telehealth condition showed a large and significant increase in knowledge about prognosis compared with those in the usual care condition (p=.036, d=1.94). Persons with schizophrenia used the Web site to a much greater extent (pages viewed and time spent) than support persons. CONCLUSIONS: These findings suggest that online delivery of psychotherapeutic treatment and educational resources to consumers' homes has considerable potential to improve consumer well-being and offers several advantages over standard clinic-based delivery models.

Mec1 function in the DNA damage response does not require its interaction with Tel2.

The essential, conserved Tel2 protein plays a role in the response to DNA damage and replication stress in a wide range of eukaryotes. Tel2 interacts physically with multiple members of the PI3-kinase related protein kinase (PIKK) family in mammalian cells and fission yeast. In mammalian cells, loss of Tel2 leads to destabilization of PIKKs. Our previous work in the yeast Saccharomyces cerevisiae showed that Tel2 interacts with the PIKK Tel1 (yeast ATM kinase), and that this interaction is abrogated by the only known non-lethal TEL2 mutation in S. cerevisiae, tel2-1. We showed that this mutation specifically disrupts the function of Tel1 and not the function of the closely related protein Mec1 (yeast ATR kinase) in DNA damage responses. Here we show that Tel2 and Mec1 interact in S. cerevisiae, and that surprisingly, this physical interaction is also disrupted by the tel2-1 mutation. Although the tel2-1 mutation leads to moderately lower Mec1 levels, the ability of Mec1 to localize to a site of DNA damage and to function in DNA damage signaling remains intact. These results suggest that the model of Tel2 as solely a global regulator of PIKK stability is insufficient. Rather, Tel2 can specifically and differentially regulate the function of individual PIKKs.

A novel Tel1/ATM N-terminal motif, TAN, is essential for telomere length maintenance and a DNA damage response.

Tel1/ATM, a conserved phosphatidylinositol 3-kinase-related kinase (PIKK), acts in the response to DNA damage and regulates telomere maintenance. PIKK family members share an extended N-terminal region of low sequence homology. Sequence alignment of the N terminus of Tel1/ATM orthologs revealed a conserved, novel motif we term TAN (for Tel1/ATM N-terminal motif). Point mutations in conserved residues of the TAN motif resulted in telomere shortening, and its deletion caused the same short telomere phenotype as complete deletion of Tel1 did. Overexpressing Tel1 TAN mutants did not rescue telomere shortening. The TAN motif was also essential for the function of Tel1 in the response to DNA damage, as TAN-deleted Tel1 was indistinguishable from the complete lack of Tel1 in causing reduced viability and signaling through Rad53 upon DNA damage. Strikingly, TAN deletion reduced recruitment of Tel1 to a double-strand DNA break. Together, these results define a conserved sequence motif within an otherwise poorly defined region of the Tel1/ATM kinase family proteins that is essential for normal Tel1 function in Saccharomyces cerevisiae.

Tel2 mediates activation and localization of ATM/Tel1 kinase to a double-strand break.

The kinases ATM and ATR (Tel1 and Mec1 in the yeast Saccharomyces cerevisiae) control the response to DNA damage. We report that S. cerevisiae Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling. We show that Tel1 and Tel2 interact, and that even when Tel1 protein levels are high, this interaction is specifically required for Tel1 localization to a DNA break and its activation of downstream targets. Computational analysis revealed structural homology between Tel2 and Ddc2 (ATRIP in vertebrates), a partner of Mec1, suggesting a common structural principle used by partners of phoshoinositide 3-kinase-like kinases.

Designing websites for persons with cognitive deficits: Design and usability of a psychoeducational intervention for persons with severe mental illness.

The purpose of this study was to develop an understanding of the design elements that influence the ability of persons with severe mental illness (SMI) and cognitive deficits to use a website, and to use this knowledge to design a web-based telehealth application to deliver a psychoeducation program to persons with schizophrenia and their families. Usability testing was conducted with 98 persons with SMI. First, individual website design elements were tested. Based on these results, theoretical website design models were used to create several alternative websites. These designs were tested for their ability to facilitate use by persons with SMI. The final website design is presented. The results indicate that commonly prescribed design models and guidelines produce websites that are poorly suited and confusing to persons with SMI. Our findings suggest an alternative model that should be considered when designing websites and other telehealth interventions for this population. Implications for future studies addressing the characteristics of accessible designs for persons with SMI and cognitive deficits are discussed.

Opposing action of estrogen receptors alpha and beta on cyclin D1 gene expression.

Induction of cyclin D1 gene transcription by estrogen receptor alpha (ERalpha) plays an important role in estrogen-mediated proliferation. There is no classical estrogen response element in the cyclin D1 promoter, and induction by ERalpha has been mapped to an alternative response element, a cyclic AMP-response element at -57, with possible participation of an activating protein-1 site at -954. The action of ERbeta at the cyclin D1 promoter is unknown, although evidence suggests that ERbeta may inhibit the proliferative action of ERalpha. We examined the response of cyclin D1 promoter constructs by luciferase assay and the response of the endogenous protein by Western blot in HeLa cells transiently expressing ERalpha, ERalphaK206A (a derivative that is superactive at alternative response elements), or ERbeta. In each case, ER activation at the cyclin D1 promoter is mediated by both the cyclic AMP-response element and the activating protein-1 site, which play partly redundant roles. The activation by ERbeta occurs only with antiestrogens. Estrogens, which activate cyclin D1 gene expression with ERalpha, inhibit expression with ERbeta. Strikingly, the presence of ERbeta completely inhibits cyclin D1 gene activation by estrogen and ERalpha or even by estrogen and the superactive ERalphaK206A. The observation of the opposing action and dominance of ERbeta over ERalpha in activation of cyclin D1 gene expression has implications for the postulated role of ERbeta as a modulator of the proliferative effects of estrogen.