Large-scale associations between the leukocyte transcriptome and BOLD responses to speech differ in autism early language outcome subtypes.

Heterogeneity in early language development in autism spectrum disorder (ASD) is clinically important and may reflect neurobiologically distinct subtypes. Here, we identified a large-scale association between multiple coordinated blood leukocyte gene coexpression modules and the multivariate functional neuroimaging (fMRI) response to speech. Gene coexpression modules associated with the multivariate fMRI response to speech were different for all pairwise comparisons between typically developing toddlers and toddlers with ASD and poor versus good early language outcome. Associated coexpression modules were enriched in genes that are broadly expressed in the brain and many other tissues. These coexpression modules were also enriched in ASD-associated, prenatal, human-specific, and language-relevant genes. This work highlights distinctive neurobiology in ASD subtypes with different early language outcomes that is present well before such outcomes are known. Associations between neuroimaging measures and gene expression levels in blood leukocytes may offer a unique in vivo window into identifying brain-relevant molecular mechanisms in ASD

A β-Catenin-Dependent Wnt Pathway Mediates Anteroposterior Axon Guidance in C. elegans Motor Neurons

Wnts are secreted glycoproteins that regulate diverse aspects of development, including cell proliferation, cell fate specification and differentiation. More recently, Wnts have been shown to direct axon guidance in vertebrates, flies and worms. However, little is known about the intracellular signaling pathways downstream of Wnts in axon guidance.Here we show that the posterior C. elegans Wnt protein LIN-44 repels the axons of the adjacent D-type motor neurons by activating its receptor LIN-17/Frizzled on the neurons. Moreover, mutations in mig-5/Disheveled, gsk-3, pry-1/Axin, bar-1/beta-catenin and pop-1/TCF, also cause disrupted D-type axon pathfinding. Reduced BAR-1/beta-catenin activity in D-type axons leads to undergrowth of axons, while stabilization of BAR-1/beta-catenin in a lin-23/SCF(beta-TrCP) mutant results in an overextension phenotype.Together, our data provide evidence that Wnt-mediated axon guidance can be transduced through a beta-catenin-dependent pathway

To transduce a zebra finch: interrogating behavioral mechanisms in a model system for speech

The ability to alter neuronal gene expression, either to affect levels of endogenous molecules or to express exogenous ones, is a powerful tool for linking brain and behavior. Scientists continue to finesse genetic manipulation in mice. Yet mice do not exhibit every behavior of interest. For example, Mus musculus do not readily imitate sounds, a trait known as vocal learning and a feature of speech. In contrast, thousands of bird species exhibit this ability. The circuits and underlying molecular mechanisms appear similar between disparate avian orders and are shared with humans. An advantage of studying vocal learning birds is that the neurons dedicated to this trait are nested within the surrounding brain regions, providing anatomical targets for relating brain and behavior. In songbirds, these nuclei are known as the song control system. Molecular function can be interrogated in non-traditional model organisms by exploiting the ability of viruses to insert genetic material into neurons to drive expression of experimenter-defined genes. To date, the use of viruses in the song control system is limited. Here, we review prior successes and test additional viruses for their capacity to transduce basal ganglia song control neurons. These findings provide a roadmap for troubleshooting the use of viruses in animal champions of fascinating behaviors-nowhere better featured than at the 12th International Congress

Psychological symptoms

Psychological symptoms are highly prevalent in people requiring palliative care. They are much more challenging to elicit, and more controversy exists about what is normal and what might require intervention than physical symptoms. There are significant issues in determining what is normal and what is not. Sadness, distress, anxiety, and depression can coexist and require careful assessment. Management of psychological symptoms and conditions can broadly be considered in terms of non-pharmacological and pharmacological therapies, “the talking and the drug therapies.” These are not mutually exclusive, and for people with limited energy, failing cognition, and limited time, some pragmatic decisions may be necessary. To be distressed and immobilized by emotion is not normal. Depression is not a normal part of dying. There should be discussion about the nature of psychological issues and conditions, explanation of common somatic symptoms, and a plan for intervention and support. The burden on the carer, both professional and personal, in such situations should not be underestimated.Gregory B. Crawfor

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

Examining the Relationship Between Supports for Youth Development and School Connectedness in a Police Athletic League After School Program

For the past twenty years , research and practice in recreation and after-school services have utilized the positive youth development (PYD) framework. PYD is guided by principles that emphasize investing in youth through the promotion of developmental assets; it steers clear of past models that view youth as risks (Benson , Scales & Syvertsen , 2011). Internal assets are outcomes for youth that include a commitment to learning , developing positive values and identity , and having social competency (Scales , Benson , Leffert & Blyth , 2000). Schools and after-school recreation programs affect internal assets by supporting external assets such as the establishment of boundaries and expectations , empowerment of youth , constructive use of time , and support from family , peers , schools , neighbors , and other adults (Scales et al.). Staff practices related to supporting developmental assets fall into four categories: (a) safe environment (e.g. , psychological and physical safety; (b) supportive environment (e.g. , skill building , conflict resolution); (c) interaction (e.g. , mentoring , fostering belonging); and (d) engagement (e.g. , opportunities to plan and lead) (Smith et al. , 2012). While there have been several studies of school-based after-school programs , there is very little research on programs run under the Police Athletic League model. The current study seeks to investigate the following research questions: (1) What program practices do PAL participants identify as important? and (2) What is the relationship between PAL program practices and youths' report of school connectedness? Results suggest that the PAL staff were performing well in all areas; however , two areas , being able to talk to staff about important things and PAL staff treating students fairly , were determined to be practices areas in which the staff could improve upon. Additionally , the results determined that a safe and supportive environment were positively correlated with school connectedness

THE IMPACT OF FORMAL AND INFORMAL CONTROLS ON RECIDIVISM IN NORWAY AND THE UNITED STATES: THE CASE OF NORTH DAKOTA PRISON EXPERIMENT

The goal of this research is to investigate to what degree the differences in recidivism rates can be accounted by differences in the dynamics of interaction between informal and formal aspects of prison organizations and their cultures in the United States and Norway. Effectiveness of prison policies as impacted by interactions of informal and formal groups within and outside the correctional systems is analyzed by using U.S. and Scandinavian Census data, official reports, and secondary literature review. Data on the North Dakota Prison Experiment was collected on a visit to two of North Dakota's correctional facilities. A counselor from the Organization for Families and Friends of Prisoners based out of Oslo, Norway was also interviewed. Scandinavian policy implications for strategies to reduce recidivism in the United States are discussed

"I Thought You Loved Me too?": Outcomes of Discrepant Involvement in Romantic Relationships

As romantic relationships begin and evolve, it is sometimes the case that partners are discrepant in their attraction to, love for, andcommitment to each other. Data were collected from 460 undergraduates who completed a 40 item Internet survey on the various types ofdiscrepancies and outcomes for their respective relationships. Results revealed that half of participants had been in a discrepantrelationship in which they were more attracted to, in love with, and committed to their partner and half were less attracted, in love andcommitted than a partner in a current or past relationship. Men were significantly more likely than women to report that they had been in adiscrepant relationship in which they were more in love with their partner. Being more attracted and less attracted, in love with, andcommitted was positively associated with infidelity. Depression was positively associated with being more or less attracted to, in love withand committed. Alcohol/drug use was positively associated with being more attracted and in love with a partner, as well as being lessattracted and committed to a partner. Of discrepant relationships that ended, 45% were by the respondent, 20% mutually, and 11% by thepartner. Of discrepant relationships that continued, 44% of the respondents reported that the discrepancies did not matter and that therespondents were happy despite the discrepancies