BackgroundSchistosomiasis is one of the most prevalent parasitic diseases worldwide and is a public health problem. Schistosoma mansoni is the most widespread species responsible for schistosomiasis in the Americas, Middle East and Africa. Adult female worms (mated to males) release eggs in the hepatic portal vasculature and are the principal cause of morbidity. Comparative separate transcriptomes of female and male adult worms were previously assessed with using microarrays and Serial Analysis of Gene Expression (SAGE), thus limiting the possibility of finding novel genes. Moreover, the egg transcriptome was analyzed only once with limited bacterially cloned cDNA libraries.Methodology/Principal findingsTo compare the gene expression of S. mansoni eggs, females, and males, we performed RNA-Seq on these three parasite forms using 454/Roche technology and reconstructed the transcriptome using Trinity de novo assembly. The resulting contigs were mapped to the genome and were cross-referenced with predicted Smp genes and H3K4me3 ChIP-Seq public data. For the first time, we obtained separate, unbiased gene expression profiles for S. mansoni eggs and female and male adult worms, identifying enriched biological processes and specific enriched functions for each of the three parasite forms. Transcripts with no match to predicted genes were analyzed for their protein-coding potential and the presence of an encoded conserved protein domain. A set of 232 novel protein-coding genes with putative functions related to reproduction, metabolism, and cell biogenesis was detected, which contributes to the understanding of parasite biology.Conclusions/SignificanceLarge-scale RNA-Seq analysis using de novo assembly associated with genome-wide information for histone marks in the vicinity of gene models constitutes a new approach to transcriptome analysis that has not yet been explored in schistosomes. Importantly, all data have been consolidated into a UCSC Genome Browser search- and download-tool (http://schistosoma.usp.br/). This database provides new ways to explore the schistosome genome and transcriptome and will facilitate molecular research on this important parasite.

Background Biobehavioural research methodology can be invasive and burdensome for participants—particularly adolescents with mental illnesses. Human biological researchers should consider how methodological impositions may hinder adolescent research participation. However, literature on adolescent’s voices and concerns toward biobehavioural research participation is virtually non-existent. Aim This study was designed to determine adolescents’ perceptions of participation in research involving the collection of biomarkers via blood, saliva and/or urine samples. Subjects and methods Urban adolescent females (aged 12–19) receiving outpatient mental health treatment (n = 37) participated in focus groups with concurrent survey administration to explore attitudes, beliefs and willingness/intentions toward biobehavioural research participation. Results Participants had favourable attitudes toward biobehavioural research and were amenable to provide each specimen type. Mistrust for research emerged, however, and concerns related to privacy and confidentiality were expressed. Conclusion Participant recruitment is a critical component in study design and implementation; this includes knowledge of population-specific recruitment barriers and facilitators. This innovative paper provides a context for the research participants’ decision-making process, strategies to allay fears and concerns and concrete areas to target in research-related interventions. Although the findings are from a specific, US-based sample, the implications warrant replication of the research in other geosocial settings.

Clinically depressed and non-depressed African American adolescent females aged 13-19 (N = 131) were interviewed and surveyed to determine the relationship between depression and HIV risk-related sexual behaviors. Narratives indicate that the psychopathology of depression may create situations where the target population could become exposed to HIV. Specifically, depressed participants described feelings of loneliness, isolation and wanting somebody to “comfort them” as aspects of depression that affect the decisions they make about sex and relationships. In essence, sex was viewed as a stress reliever, an anti-depressant and a way to increase self-esteem. They shared that even if they didn't feel like having sex, they might just “git it over wit” so they're partners would stop asking. Some also discussed financial and emotional stability offered by older, more sexually experienced partners. These age-discordant relationships often translated into trusting that their partners knew what was best for their sexual relationships (i.e. having unprotected sex). Sixty-nine percent (n = 88) of the sample reported engaging in sexual activity. Given their mean age (16 ± 1.9) participants had been sexually active for 2 ± 1.8 years. The adolescents reported an average of 2 ± 1.8 sexual partners within the past three months. Depressed participants reported a higher frequency of having ever had sex (78% vs. 59%, X2= 5.236, p = .022), and had a higher mean number of sexual partners (2 vs. 1, t= −2.023, p= .048) and sexual encounters under the influence of drugs and alcohol (8 vs. 2, t= −3.078, p = .005) in the past three months. The results of this study can guide the modification and/or development of tailored HIV/STI prevention programs. The findings provide explicit, psychologically and culturally relevant information regarding the interaction between depression, self-medicating behaviors and risk for HIV/STIs among clinically depressed African American adolescent females.

Leishmaniasis is an infectious disease caused by Leishmania species. Leishmania amazonensis is a New World Leishmania species belonging to the Mexicana complex, which is able to cause all types of leishmaniasis infections. The L. amazonensis reference strain MHOM/BR/1973/M2269 was sequenced identifying 8,802 codifying sequences (CDS), most of them of hypothetical function. Comparative analysis using six Leishmania species showed a core set of 7,016 orthologs. L. amazonensis and Leishmania mexicana share the largest number of distinct orthologs, while Leishmania braziliensis presented the largest number of inparalogs. Additionally, phylogenomic analysis confirmed the taxonomic position for L. amazonensis within the “Mexicana complex”, reinforcing understanding of the split of New and Old World Leishmania. Potential non-homologous isofunctional enzymes (NISE) were identified between L. amazonensis and Homo sapiens that could provide new drug targets for development.

BackgroundSchistosomiasis is a parasitic disease infecting hundreds of millions of people worldwide. Treatment depends on a single drug, praziquantel, which kills the Schistosoma spp. parasite only at the adult stage. HDAC inhibitors (HDACi) such as Trichostatin A (TSA) induce parasite mortality in vitro (schistosomula and adult worms), however the downstream effects of histone hyperacetylation on the parasite are not known.Methodology/Principal findingsTSA treatment of adult worms in vitro increased histone acetylation at H3K9ac and H3K14ac, which are transcription activation marks, not affecting the unrelated transcription repression mark H3K27me3. We investigated the effect of TSA HDACi on schistosomula gene expression at three different time points, finding a marked genome-wide change in the transcriptome profile. Gene transcription activity was correlated with changes on the chromatin acetylation mark at gene promoter regions. Moreover, combining expression data with ChIP-Seq public data for schistosomula, we found that differentially expressed genes having the H3K4me3 mark at their promoter region in general showed transcription activation upon HDACi treatment, compared with those without the mark, which showed transcription down-regulation. Affected genes are enriched for DNA replication processes, most of them being up-regulated. Twenty out of 22 genes encoding proteins involved in reducing reactive oxygen species accumulation were down-regulated. Dozens of genes encoding proteins with histone reader motifs were changed, including SmEED from the PRC2 complex. We targeted SmEZH2 methyltransferase PRC2 component with a new EZH2 inhibitor (GSK343) and showed a synergistic effect with TSA, significantly increasing schistosomula mortality.Conclusions/SignificanceGenome-wide gene expression analyses have identified important pathways and cellular functions that were affected and may explain the schistosomicidal effect of TSA HDACi. The change in expression of dozens of histone reader genes involved in regulation of the epigenetic program in S. mansoni can be used as a starting point to look for possible novel schistosomicidal targets.

Purpose The purpose was to evaluate the effectiveness of SHARP, an academic asthma health education and counseling program, on fostering use of effective asthma self-care behaviors. Design and Methods This was a phase III, two-group, cluster randomized, single-blinded, longitudinal design guided the study. Caregivers of 205 fourth- and fifth-grade students completed the asthma health behaviors survey at pre-intervention and 1, 12, and 24 months post-intervention. Analysis involved multilevel modeling. Results All students demonstrated improvement in episode management, risk-reduction/prevention, and health promotion behaviors; SHARP students demonstrated increased improvement in episode management and risk-reduction/prevention behaviors. Practice Implications Working with schoolteachers, nurses can improve use of effective asthma self-care behaviors.

Problem-To examine if the experience of peer relational aggression victimization can be linked to feelings of depression in the African American adolescent female population.Method-The sample included 241 African American college age adolescent females assessed for peer relational aggression victimization (PRAV) and depression. Statistical analysis was done to determine the relationship between the variables.Findings-PRAV, in this study population does exist as a detrimental phenomenon whereby PRAV significantly correlates with depression, r (214) = .29, p < .01. Conclusion-Nursescan assist the adolescent client experiencing relational aggression by becoming knowledgeable on the presentation and manifestations of this experience.

Effective B cell responses such as cytokine secretion, proliferation, and Ab-specific responses are essential to clear hepatitis B virus (HBV) infection. However, HBV alters numerous immune pathways to persist in the host. B cell activity depends on activation of the innate sensor TLR9 by viral or bacterial DNA motifs. How HBV can deregulate B cell functions remains unknown. In this study, we show that HBV can enter and decrease TLR9 expression in human primary B cells. Using PBMCs from human blood donors, we show that TLR9 expression was reduced in all peripheral B cells subsets exposed to HBV. B cell function mediated by TLR9, but not TLR7, such as proliferation and proinflammatory cytokines secretion, were abrogated in the presence of HBV; however, global Ig secretion was not downregulated. Mechanistically, we show, using human myeloma B cell line RPMI 8226, that the surface Ag hepatitis B surface Ag was responsible for TLR9 dysfunction. hepatitis B surface Ag suppressed the phosphorylation and thus the activation of the transcription factor CREB, preventing TLR9 promoter activity. Finally, we corroborated our in vitro findings in a cohort of chronic HBV carriers and found that TLR9 expression and function were significantly suppressed. The effect of HBV on TLR9 activity in B cells gives insights into oncoviral immune escape strategies, providing knowledge to develop novel immunotherapeutic approaches in chronic HBV-carrier patients.