A transcription factor DAF-5 functions in Haemonchus contortus development.

BACKGROUND: Abnormal dauer formation gene (daf-5), located downstream of the DAF-7 signalling pathway, mainly functions in dauer formation and reproductive processes in the free-living nematode Caenorhabditis elegans. Although the structure and function of daf-5 have been clarified in C. elegans, they still remain totally unknown in Haemonchus contortus, a socio-economically important parasitic nematode of gastric ruminants. METHODS: A homologue of daf-5, Hc-daf-5, and its inferred product (Hc-DAF-5) in H. contortus were identified and characterized in this study. Then the transcriptional profiles of Hc-daf-5 and the anatomical expression of Hc-DAF-5 in H. contortus were studied using an integrated molecular approach. RNA interference (RNAi) was performed to explore its function in transition from the exsheathed third-stage larvae (xL3s) to the fourth-stage larvae (L4s) in vitro. Finally, the interaction between Hc-DAF-5 and Hc-DAF-3 (a co-Smad) was detected by bimolecular fluorescence complementation (BiFc) in vitro. RESULTS: It was shown that Hc-DAF-5 was a member of the Sno/Ski superfamily. Hc-daf-5 was transcribed in all developmental stages of H. contortus, with significant upregulation in L3s. Native Hc-DAF-5 was localized in the reproductive organs, cuticle, and intestine via immunohistochemistry. RNAi revealed that specific small interfering RNAs (siRNAs) could retard xL3 development. In addition, the interaction between Hc-DAF-5 and Hc-DAF-3 indicated that the SDS box of Hc-DAF-5 was dispensable for the binding of Hc-DAF-5 to Hc-DAF-3, and the MH2 domain was the binding region between Hc-DAF-3 and Hc-DAF-5. CONCLUSIONS: In summary, these findings show that Hc-daf-5 functions in the developmental processes of H. contortus, and this study is the first attempt to characterize the daf-5 gene in parasitic nematodes.

PPAR-γ Is Critical for HDAC3-Mediated Control of Oligodendrocyte Progenitor Cell Proliferation and Differentiation after Focal Demyelination.

Disruption of remyelination contributes to neurodegeneration and cognitive impairment in chronically disabled patients. Valproic acid (VPA) inhibits histone deacetylase (HDAC) function and probably promotes oligodendrocyte progenitor cell (OPC) proliferation and differentiation; however, the relevant molecular mechanisms remain unknown. Here, focal demyelinating lesions (FDLs) were generated in mice by two-point stereotactic injection of lysophosphatidylcholine (LPC) into the corpus callosum. Cognitive functions, sensorimotor abilities and histopathological changes were assessed for up to 28 days post-injury with or without VPA treatment. Primary OPCs were harvested and used to study the effect of VPA on OPC differentiation under inflammatory conditions. VPA dose-dependently attenuated learning and memory deficits and robustly protected white matter after FDL induction, as demonstrated by reductions in SMI-32 and increases in myelin basic protein staining. VPA also promoted OPC proliferation and differentiation and increased subsequent remyelination efficiency by day 28 post-FDL induction. VPA treatment did not affect HDAC1, HDAC2 or HDAC8 expression but reduced HDAC3 protein levels. In vitro, VPA improved the survival of mouse OPCs and promoted their differentiation into oligodendrocytes following lipopolysaccharide (LPS) stimulation. LPS caused OPCs to overexpress HDAC3, which translocated from the cytoplasm into the nucleus, where it directly interacted with the nuclear transcription factor PPAR-γ and negatively regulated PPAR-γ expression. VPA decreased the expression of HDAC3 and promoted remyelination and functional neurological recovery after FDL. These findings may support the use of strategies modulating HDAC3-mediated regulation of protein acetylation for the treatment of demyelination-related cognitive dysfunction.

Tobacco-Nicotine Education and Training for Health-Care Professional Students and Practitioners: A Systematic Review.

Introduction: The objective of this systematic review was to investigate what education and training characteristics prepares and supports health-care professionals (HCPs) in the delivery of competent and effective care to clients who use tobacco-nicotine. Aims and Methods: A search of eight bibliographic databases for English-language peer-reviewed publications from January 2006 to March 2015. Studies were included if they met the a priori inclusion criteria, which consisted of: (1) quantitative study design and (2) focus on tobacco-nicotine education or training for HCP students and practitioners. All studies were independently screened for inclusion by two reviewers. Data from included studies were extracted for study characteristics and key outcomes then critically appraised for methodological quality. Results: Fifty-nine studies were included for narrative synthesis. Two categories emerged: (1) curriculum characteristics (n = 10) and (2) education and training interventions (n = 49). Included curriculum studies identified the following themes: content, intensity, competencies evaluation, and barriers. Study findings about education and training interventions were grouped by level of education (prelicensure, post-licensure, and faculty training), teaching modality, health discipline, and the associated HCP and client outcomes. Conclusions: This comprehensive review suggests that there is a lack of consistency in HCP tobacco-nicotine education and training characteristics. This paper provides valuable categorization of the most frequently utilized components of academic curriculum and discusses the interventions in relation to HCP and client outcomes. Gaps in the literature are highlighted, and the need for standardization of tobacco-nicotine training competencies and evaluation is discussed. Future research investigating the most effective approaches to training is needed. Implications: This systematic review summarizes existing tobacco-related curriculum components (content, intensity, competency evaluation, and barriers) and training interventions for health-care professionals worldwide and demonstrates that they are associated with positive health-care professional outcomes (knowledge, attitudes, behaviors, and skills) and client outcomes (quit attempts and smoking abstinence).