Do echinoderm genomes measure up?

Echinoderm genome sequences are a corpus of useful information about a clade of animals that serve as research models in fields ranging from marine ecology to cell and developmental biology. Genomic information from echinoids has contributed to insights into the gene interactions that drive the developmental process at the molecular level. Such insights often rely heavily on genomic information and the kinds of questions that can be asked thus depend on the quality of the sequence information. Here we describe the history of echinoderm genomic sequence assembly and present details about the quality of the data obtained. All of the sequence information discussed here is posted on the echinoderm information web system, Echinobase.org.

Genenames.org: the HGNC resources in 2013.

The HUGO Gene Nomenclature Committee situated at the European Bioinformatics Institute assigns unique symbols and names to human genes. Since 2011, the data within our database has expanded largely owing to an increase in naming pseudogenes and non-coding RNA genes, and we now have >33,500 approved symbols. Our gene families and groups have also increased to nearly 500, with ∼45% of our gene entries associated to at least one family or group. We have also redesigned the HUGO Gene Nomenclature Committee website http://www.genenames.org creating a constant look and feel across the site and improving usability and readability for our users. The site provides a public access portal to our database with no restrictions imposed on access or the use of the data. Within this article, we review our online resources and data with particular emphasis on the updates to our website.

Gender research in the National Institute on Drug Abuse National Treatment Clinical Trials Network: a summary of findings.

BACKGROUND: The National Institute of Drug Abuse's National Drug Abuse Treatment Clinical Trials Network (CTN) was established to foster translation of research into practice in substance abuse treatment settings. The CTN provides a unique opportunity to examine in multi-site, translational clinical trials, the outcomes of treatment interventions targeting vulnerable subgroups of women; the comparative effectiveness of gender-specific protocols to reduce risk behaviors; and gender differences in clinical outcomes. OBJECTIVES: To review gender-related findings from published CTN clinical trials and related studies from January 2000 to March 2010. METHODS: CTN studies were selected for review if they focused on treatment outcomes or services for special populations of women with substance use disorders (SUDs) including those with trauma histories, pregnancy, co-occurring eating and other psychiatric disorders, and HIV risk behaviors; or implemented gender-specific protocols. The CTN has randomized 11,500 participants (41% women) across 200 clinics in 24 randomized controlled trials in community settings, of which 4 have been gender-specific. RESULTS: This article summarizes gender-related findings from CTN clinical trials and related studies, focusing on trauma histories, pregnancy, co-occurring eating and other psychiatric disorders, and HIV risk behaviors. CONCLUSIONS: These published studies have expanded the evidence base regarding interventions for vulnerable groups of women with SUDs as well as gender-specific interventions to reduce HIV risk behaviors in substance-using men and women. The results also underscore the complexity of accounting for gender in the design of clinical trials and analysis of results. SCIENTIFIC SIGNIFICANCE: To fully understand the relevance of gender-specific moderators and mediators of outcome, it is essential that future translational studies adopt more sophisticated approaches to understanding and measuring gender-relevant factors and plan sample sizes that are adequate to support more nuanced analytic methods.

genenames.org: the HGNC resources in 2011.

The HUGO Gene Nomenclature Committee (HGNC) aims to assign a unique gene symbol and name to every human gene. The HGNC database currently contains almost 30,000 approved gene symbols, over 19,000 of which represent protein-coding genes. The public website, www.genenames.org, displays all approved nomenclature within Symbol Reports that contain data curated by HGNC editors and links to related genomic, phenotypic and proteomic information. Here we describe improvements to our resources, including a new Quick Gene Search, a new List Search, an integrated HGNC BioMart and a new Statistics and Downloads facility.

Substance abuse treatment entry, retention, and outcome in women: a review of the literature.

This paper reviews the literature examining characteristics associated with treatment outcome in women with substance use disorders. A search of the English language literature from 1975 to 2005 using Medline and PsycInfo databases found 280 relevant articles. Ninety percent of the studies investigating gender differences in substance abuse treatment outcomes were published since 1990, and of those, over 40% were published since the year 2000. Only 11.8% of these studies were randomized clinical trials. A convergence of evidence suggests that women with substance use disorders are less likely, over the lifetime, to enter treatment compared to their male counterparts. Once in treatment, however, gender is not a significant predictor of treatment retention, completion, or outcome. Gender-specific predictors of outcome do exist, however, and individual characteristics and treatment approaches can differentially affect outcomes by gender. While women-only treatment is not necessarily more effective than mixed-gender treatment, some greater effectiveness has been demonstrated by treatments that address problems more common to substance-abusing women or that are designed for specific subgroups of this population. There is a need to develop and test effective treatments for specific subgroups such as older women with substance use disorders, as well as those with co-occurring substance use and psychiatric disorders such as eating disorders. Future research on effectiveness and cost-effectiveness of gender-specific versus standard treatments, as well as identification of the characteristics of women and men who can benefit from mixed-gender versus single-gender treatments, would advance the field.

Inpatient desire to drink as a predictor of relapse to alcohol use following treatment.

Cravings for alcohol are identified as a trigger for relapse, though laboratory studies of cravings produce mixed results in predicting relapse. The objective of this analysis is to assess the usefulness of craving as a predictor of relapse by assessing 218 adult, alcohol-dependent patients admitted to two separate residential addiction treatment programs. Days craving reported in the week prior to discharge predicted alcohol use at three-month follow-up. Admission spirituality, alcohol-refusal self-efficacy, and depression levels differentiated cravers from non-cravers. Patients who crave alcohol in residential treatment may be at higher relapse risk and identified by intake assessments of self-efficacy, depression, and spirituality.

Levels of spirituality and treatment outcome: a preliminary examination.

OBJECTIVE: The primary aim of this study was to examine whether admission differences in levels of spirituality predisposed alcohol-dependent individuals to favorable or unfavorable outcomes following admission to facilities that differed in the degree to which spirituality was emphasized. It was hypothesized that individuals whose admission level of spirituality was congruent with the treatment program's orientation and who as such were considered optimally placed (i.e., "matched") for treatment would evince better in-treatment outcomes. METHOD: Four hundred and five participants completed measures of spirituality and psychosocial well-being at intake and at end of treatment. RESULTS: In examining the entire sample, no matching effects were observed on discharge status, abstinence efficacy, or desire to drink. When analyses were restricted to those cases scoring in the upper or lower quartiles in spirituality, we observed a paradoxical effect, as individuals recording lower levels of spirituality at the less spiritual program evinced significantly poorer outcomes (i.e., less abstinence efficacy, greater desire to drink). CONCLUSIONS: These findings hint at the importance of spirituality in the environment of care, indicating that individuals low in spirituality were at risk for poorer outcomes, but exposure to a program that emphasized spirituality lowered that risk.

Tetratricopeptide-motif-mediated interaction of FANCG with recombination proteins XRCC3 and BRCA2.

Fanconi anaemia is an inherited chromosomal instability disorder characterised by cellular sensitivity to DNA interstrand crosslinkers, bone-marrow failure and a high risk of cancer. Eleven FA genes have been identified, one of which, FANCD1, is the breast cancer susceptibility gene BRCA2. At least eight FA proteins form a nuclear core complex required for monoubiquitination of FANCD2. The BRCA2/FANCD1 protein is connected to the FA pathway by interactions with the FANCG and FANCD2 proteins, both of which co-localise with the RAD51 recombinase, which is regulated by BRCA2. These connections raise the question of whether any of the FANC proteins of the core complex might also participate in other complexes involved in homologous recombination repair. We therefore tested known FA proteins for direct interaction with RAD51 and its paralogs XRCC2 and XRCC3. FANCG was found to interact with XRCC3, and this interaction was disrupted by the FA-G patient derived mutation L71P. FANCG was co-immunoprecipitated with both XRCC3 and BRCA2 from extracts of human and hamster cells. The FANCG-XRCC3 and FANCG-BRCA2 interactions did not require the presence of other FA proteins from the core complex, suggesting that FANCG also participates in a DNA repair complex that is downstream and independent of FANCD2 monoubiquitination. Additionally, XRCC3 and BRCA2 proteins co-precipitate in both human and hamster cells and this interaction requires FANCG. The FANCG protein contains multiple tetratricopeptide repeat motifs (TPRs), which function as scaffolds to mediate protein-protein interactions. Mutation of one or more of these motifs disrupted all of the known interactions of FANCG. We propose that FANCG, in addition to stabilising the FA core complex, may have a role in building multiprotein complexes that facilitate homologous recombination repair.

FANCC, FANCE, and FANCD2 form a ternary complex essential to the integrity of the Fanconi anemia DNA damage response pathway.

Fanconi anemia (FA) is a genetically heterogeneous disorder characterized by bone marrow failure, cancer predisposition, and increased cellular sensitivity to DNA-cross-linking agents. The products of seven of the nine identified FA genes participate in a protein complex required for monoubiquitination of the FANCD2 protein. Direct interaction of the FANCE protein with both fellow FA complex component FANCC and the downstream FANCD2 protein has been observed in the yeast two-hybrid system. Here, we demonstrate the ability of FANCE to mediate the interaction between FANCC and FANCD2 in the yeast three-hybrid system and confirm the FANCE-mediated association of FANCC with FANCD2 in human cells. A yeast two-hybrid system-based screen was devised to identify randomly mutagenized FANCE proteins capable of interaction with FANCC but not with FANCD2. Exogenous expression of these mutants in an FA-E cell line and subsequent evaluation of FANCD2 monoubiquitination and DNA cross-linker sensitivity indicated a critical role for the FANCE/FANCD2 interaction in maintaining FA pathway integrity. Three-hybrid experiments also demonstrated the ability of FANCE to mediate the interaction between FA core complex components FANCC and FANCF, indicating an additional role for FANCE in complex assembly. Thus, FANCE is shown to be a key mediator of protein interactions both in the architecture of the FA protein complex and in the connection of complex components to the putative downstream targets of complex activity.

Characteristics of adolescents in residential treatment for heroin dependence.

A retrospective review of the clinical charts of 97 adolescents who had received residential treatment for heroin dependence was conducted to determine predictors of heroin use. The average age for the adolescent patients reviewed was 17 years. Almost half of the adolescents (48%) were female and over half of the adolescents (53.6%) used heroin intravenously. Both males and females had substantial heroin habits, but differing amounts of use. Boys used an average of six bags of heroin per day and girls used an average of four bags of heroin per day. Using gender, age, number of heroin dependence symptoms, and other substances as predictors, 64.21% of the adolescents were correctly classified as injectors or noninjectors of heroin. Heroin appears to be a significant drug of abuse among these predominately white, middle class, suburban adolescents.

Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems.

Fanconi anemia (FA) is an autosomal recessive syndrome characterized by progressive bone marrow failure and cancer predisposition. Eight FA complementation groups have been identified. The FANCA, FANCC, FANCE, FANCF, and FANCG proteins form a nuclear complex required for the monoubiquination of the FANCD2 protein. To investigate the architecture of the FA protein complex, the yeast 2-hybrid system was used to map contact points of the FANCA/FANCG, FANCC/FANCE, and FANCF/FANCG interactions. FANCG was shown to interact with both the amino-terminus of FANCA and the carboxyl-terminal region of FANCF. A FANCG mutant truncated at the carboxyl-terminus retained the ability to interact with FANCA. The interaction between FANCG and FANCF was ablated by a Leu71Pro mutant of FANCG. A central region of FANCE was sufficient for FANCC binding. A Leu554Pro mutant of FANCC failed to interact with FANCE. To further examine complex assembly, the yeast 3-hybrid system was used to investigate the ability of FANCG to act as a molecular bridge in mediating interaction between other FA proteins. FANCG was able to mediate interaction between FANCA and FANCF, as well as between monomers of FANCA. Direct interaction between FANCE and FANCD2 was also demonstrated in the yeast 2-hybrid system. This interaction involving an amino-terminal region of FANCD2 may provide a link between the FA protein complex and its downstream targets.