64 research outputs found
Overexpression of interferon alpha or beta receptors in the brain of adult Ts1Cje mouse model of Down syndrome
Introduction: Down syndrome (DS) is a generic disorder with trisomy of human chromosome 21 (HSA21) and all DS patients exhibited intellectual disability. Ts1Cje mouse model of DS has partial triplication of mouse chromosome 16 (MMU16) which is homologous to HSA21. The JAK (Janus kinase) and STAT (signal transducer and activator of transcription) signalling pathway is involved in neurogenesis and gliogenesis regulation. Cytokines especially the interferons (IFN) family is the major activator of JAK-STAT signalling pathway. Furthermore, interferon receptor genes (Ifnar), Ifnar2 and Ifngr2 are located at the triplicated region in MMU16 and also in HSA21.
Method: Gene expression of Ifnar1, Ifnar2, Ifngr2 and associated genes in JAK-STAT signalling pathway (Jak1, Jak2, Stat1, Stat3 and Stat6) in the cerebral cortex and cerebellum between Ts1Cje and wild type control at four time-points; post natal day (P)1, P15, P30 and P84 was investigated by using qRT-PCR techniques. Western blotting was used to confirm the overexpression of Ifnar1, Ifnar2 and Stat1 in the cerebral cortex and cerebellum of Ts1Cje aged P84.
Results: Ifnar1, Ifnar2, Ifngr2 and Stat1 were significantly overexpression in the cerebral cortex and cerebellum of Ts1Cje at various time points as compared to control littermates. Protein expression analysis confirmed the overexpression of Ifnar1 and Stat1 in the cerebellum of Ts1Cje mouse at P84 as compared to wild type. The findings suggest that overexpression of interferon receptors will increase sensitivity towards interferon levels in Ts1Cje mouse brain. Consequently, the over-stimulated JAK-STAT signalling pathway may contribute to the defective neurogenesis the Down syndrome mouse brain
Molecular networks involved in mouse cerebral corticogenesis and spatio-temporal regulation of Sox4 and Sox11 novel antisense transcripts revealed by transcriptome profiling.
Background:
Development of the cerebral cortex requires highly specific spatio-temporal regulation of gene expression. It is proposed that transcriptome profiling of the cerebral cortex at various developmental time points or regions will reveal candidate genes and associated molecular pathways involved in cerebral corticogenesis.
Results:
Serial analysis of gene expression (SAGE) libraries were constructed from C57BL/6 mouse cerebral cortices of age embryonic day (E) 15.5, E17.5, postnatal day (P) 1.5 and 4 to 6 months. Hierarchical clustering analysis of 561 differentially expressed transcripts showed regionalized, stage-specific and co-regulated expression profiles. SAGE expression profiles of 70 differentially expressed transcripts were validated using quantitative RT-PCR assays. Ingenuity pathway analyses of validated differentially expressed transcripts demonstrated that these transcripts possess distinctive functional properties related to various stages of cerebral corticogenesis and human neurological disorders. Genomic clustering analysis of the differentially expressed transcripts identified two highly transcribed genomic loci, Sox4 and Sox11, during embryonic cerebral corticogenesis. These loci feature unusual overlapping sense and antisense transcripts with alternative polyadenylation sites and differential expression. The Sox4 and Sox11 antisense transcripts were highly expressed in the brain compared to other mouse organs and are differentially expressed in both the proliferating and differentiating neural stem/progenitor cells and P19 (embryonal carcinoma) cells.
Conclusions:
We report validated gene expression profiles that have implications for understanding the associations between differentially expressed transcripts, novel targets and related disorders pertaining to cerebral corticogenesis. The study reports, for the first time, spatio-temporally regulated Sox4 and Sox11 antisense transcripts in the brain, neural stem/progenitor cells and P19 cells, suggesting they have an important role in cerebral corticogenesis and neuronal/glial cell differentiation
Therapeutic Down-Modulators of Staphylococcal Superantigen-Induced Inflammation and Toxic Shock
Staphylococcal enterotoxin B (SEB) and related superantigenic toxins are potent stimulators of the immune system and cause a variety of diseases in humans, ranging from food poisoning to toxic shock. These toxins bind directly to major histocompatibility complex (MHC) class II molecules on antigen-presenting cells and specific Vβ regions of T-cell receptors (TCR), resulting in hyperactivation of both monocytes/macrophages and T lymphocytes. Activated host cells produce massive amounts of proinflammatory cytokines and chemokines, activating inflammation and coagulation, causing clinical symptoms that include fever, hypotension, and shock. This review summarizes the in vitro and in vivo effects of staphylococcal superantigens, the role of pivotal mediators induced by these toxins in the pathogenic mechanisms of tissue injury, and the therapeutic agents to mitigate the toxic effects of superantigens
Electronic reminders did not improve postal questionnaire response rates or response times: a randomized controlled trial
OBJECTIVE: We aim to evaluate the effectiveness of electronic reminders (ERs) to improve the response rates and time to response of postal questionnaires in a health research setting. STUDY DESIGN AND SETTING: This pragmatic randomized controlled trial (RCT) was nested within a multicenter RCT of yoga for lower back pain. Participants who provided an electronic mail address and/or mobile phone number were randomized to receive an ER or no reminder (controls) on the day they were due to receive a follow-up questionnaire. RESULTS: One hundred twenty-five participants (32 males and 93 females) mean age 46 (standard deviation: 11, range: 20-65) were randomized to ER (n=62) or controls (n=63). Overall 85.6% of participants returned postal questionnaires (87.1% ER group and 84.1% from controls). No significant differences were found between the two groups for response rate (difference between groups=3.0%, 95% confidence interval [CI]=-10, 16; P=0.64) or time to response after adjusting for age, gender, and treatment allocation (χ(2) ([3df])=7.10; P=0.07). CONCLUSION: In the present RCT, we found little evidence for the effectiveness of ERs to increase response rates or time to respond for the return of questionnaires in this study population group
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