Stage-specific functions of Semaphorin7A during adult hippocampal neurogenesis rely on distinct receptors

The guidance protein Semaphorin7A (Sema7A) is required for the proper development of the immune and nervous systems. Despite strong expression in the mature brain, the role of Sema7A in the adult remains poorly defined. Here we show that Sema7A utilizes different cell surface receptors to control the proliferation and differentiation of neural progenitors in the adult hippocampal dentate gyrus (DG), one of the select regions of the mature brain where neurogenesis occurs. PlexinC1 is selectively expressed in early neural progenitors in the adult mouse DG and mediates the inhibitory effects of Sema7A on progenitor proliferation. Subsequently, during differentiation of adult-born DG granule cells, Sema7A promotes dendrite growth, complexity and spine development through β1-subunit-containing integrin receptors. Our data identify Sema7A as a key regulator of adult hippocampal neurogenesis, providing an example of how differential receptor usage spatiotemporally controls and diversifies the effects of guidance cues in the adult brain

Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as novel risk factors for Alzheimers Disease

The genetic component of Alzheimer’s disease (AD) has been mainly assessed using Genome Wide Association Studies (GWAS), which do not capture the risk contributed by rare variants. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals —16,036 AD cases and 16,522 controls— in a two-stage analysis. Next to known genes TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Next to these genes, the rare variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential driver genes in AD-GWAS loci. Rare damaging variants in these genes, and in particular loss-of-function variants, have a large effect on AD-risk, and they are enriched in early onset AD cases. The newly identified AD-associated genes provide additional evidence for a major role for APP-processing, Aβ-aggregation, lipid metabolism and microglial function in AD

Risk indicators for depressed mood in urban youth : the role of socioeconomic and cultural status

Socioeconomic status and Aboriginal cultural status are believed to be key risk indicators of mental health status in youth.The main purpose of the study was to explore the role of Aboriginal cultural status as an independent risk indicator associated with depressed mood after controlling for other covariates; including socioeconomic status. Methods A population based cross sectional survey was used. Every student in grades 5-8 in Saskatoon was asked to complete a short self-report questionnaire in their classroom in February of 2007. Depressed mood was measured with a validated depression scale (CES-D-12).Results In total, 4093 adolescents completed the study questionnaire. For youth whose parents were of Aboriginal cultural status, the prevalence rate of moderate or severe depressed mood was 21.6% in comparison to 8.9% for youth whose parents were Caucasian (RR=2.43; 95% CI 1.92-3.08). In the final adjusted multivariate logistic regression model, moderate or severe depressed mood was more likely to be associated with female gender (OR=1.665; 95% CI 1.179-2.352), having low self esteem (OR=3.185; 95% CI 2.084-4.870), feeling like an outsider at school (OR=3.364; 95% CI 2.386-4.743), being bullied within the past year (OR=1.879; 95% CI 1.278-2.761), alcohol usage (OR=2.518; 95% CI 1.730-3.666), high levels of anxiety (OR=22.171; 95% CI 14.170-34.960), suicide ideation (OR=3.734; 95% CI 2.502-5.572), being hungry some or most of the time (OR=2.071; 95% CI 1.357-3.162) and parents having a lower education status (OR=1.503; 95% CI 1.066-2.120). Although Aboriginal cultural status was strongly associated with moderate or severe depressed mood after cross tabulation and stratification, Aboriginal cultural status was not associated with higher levels of depressed mood after full adjustment for other covariates in the final multivariate model (OR= 1.132; 95% CI 0.682-1.881).ConclusionsThe results demonstrate that Aboriginal cultural status has a more limited and statistically non-significant association with moderate or severe depressed mood in youth after controlling for other covariates. There is a need to transfer the results of this research to the Saskatoon community to allow policy makers and the public at large to know that prevention of disparity in mental health is possible because the determinants of mental health (i.e., education) are now modifiable (in comparison to Aboriginal cultural status)

Third-world realities in a first-world setting: A study of the HIV/AIDS-related conditions and risk behaviors of sex trade workers in Saskatoon, Saskatchewan, Canada

The transmission and prevalence of Human Immunodeficiency Virus (HIV) among those employed as sex trade workers (STW) is a major public health concern. The present study describes the self-reported responses of 340 STW, at-risk for contracting HIV. The participants were recruited by selective targeting between 2009 and 2010 from within the Saskatoon Health Region (SHR), Saskatchewan, Canada. As of 2012, the SHR has the highest incidence rate of positive test reports for HIV in Canada, at more than three times the national average (17.0 vs. 5.9 per 100,000 people). Additionally, the epidemiology of HIV/AIDS in the SHR is different from that seen elsewhere in Canada (still mostly men having sex with men and Caucasians), with its new HIV cases predominantly associated with injection drug use and Aboriginal cultural status. The purpose of this study was to (a) describe the demographic and socio-economic characteristics of the STW in the SHR, (b) identify their significant life events, self-reported problems, knowledge, attitudes, behaviors, self-efficacy, and barriers regarding HIV, and (c) determine the significant independent risk indicators for STW self-reporting a chance of greater than 50% of becoming infected with HIV/AIDS. The majority of the study participants were females, who were never married, of Aboriginal descent, without a high school diploma, and had an annual income of less than $10,000. Using multivariate regression analysis, four significant independent risk indicators were associated with STW reporting a greater that 50% chance of acquiring HIV/AIDS, including experiencing sexual assault as a child, injecting drugs in the past four weeks, being homeless, and a previous Chlamydia diagnosis. These findings provide important evidence of the essential sexual and drug-related vulnerabilities associated with the risk of HIV infection among STW and offer insight into the design and implementation of effective and culturally sensitive public health intervention and prevention efforts. To be most effective, it is recommended that such intervention and prevention initiatives: (1) use specifically tailored community-based outreach to high risk STW who are drug users and link them with appropriate drug treatment and HIV/AIDS prevention and treatment services, (2) provide free and confidential, routine HIV counseling and testing in substance abuse programs, and (3) build capacity among the local, Aboriginal NGOs so as to address with cultural sensitivity both the drug and HIV-related risk factors prevalent among this vulnerable population

Daily smoking in Saskatoon: the independent effect of income and cultural status

OBJECTIVE: Smoking prevalence in the Saskatoon Health Region (SHR) went from 23.9% in 2003 to 23.3% in 2005 to 26.2% in 2007. The prevalence of smoking within the SHR Aboriginal population is substantially higher than the rest of the population. The purpose of the current study was to determine the independent effects of Aboriginal cultural status and income status on daily smoking status. METHODS: Data from three cycles of the Canadian Community Health Survey (2001, 2003, 2005) were merged with identical data collected by the SHR in 2007. All four cycles were random telephone survey samples. RESULTS: 5948 participants (81.1% response rate) completed the survey. After cross-tabulation, Aboriginal cultural status and income were strongly associated with daily smoking status. Using logistic regression, the odds of daily smoking for residents of Aboriginal cultural status was reduced substantially from the initial odds of 3.43 to 2.26 after adjusting for income alone, and reduced further to 1.57 after full multivariate adjustment. CONCLUSION: Given the association between smoking status and income status, future policies to reduce smoking prevalence should include generic policies to reduce income disparity as well as targeted strategies to improve the social conditions of Aboriginal peopl