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Selected AbstractsLRRN6A/LERN1 (leucine-rich repeat neuronal protein 1), a novel gene with enriched expression in limbic system and neocortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2003Laura Carim-Todd Abstract Human chromosome 15q24-q26 is a very complex genomic region containing several blocks of segmental duplications to which susceptibility to anxiety disorders has been mapped (Gratacos et al., 2001, Cell, 106, 367,379; Pujana et al., 2001, Genome Res., 11, 98,111). Through an in silico gene content analysis of the 15q24-q26 region we have identifie1d a novel gene, LRRN6A (leucine-rich repeat neuronal 6A), and confirmed its location to the centromeric end of this complex region. LRRN6A encodes a transmembrane leucine-rich repeat protein, LERN1 (leucine-rich repeat neuronal protein 1), with similarity to proteins involved in axonal guidance and migration, nervous system development and regeneration processes. The identification of homologous genes to LRRN6A on chromosomes 9 and 19 and the orthologous genes in the mouse genome and other organisms suggests that LERN proteins constitute a novel subfamily of LRR (leucine-rich repeat)-containing proteins. The LRRN6A expression pattern is specific to the central nervous system, highly and broadly expressed during early stages of development and gradually restricted to forebrain structures as development proceeds. Expression level in adulthood is lower in general but remains stable and significantly enriched in the limbic system and cerebral cortex. Taken together, the confirmation of LRRN6A's expression profile, its predicted protein structure and its similarity to nervous system-expressed LRR proteins with essential roles in nervous system development and maintenance suggest that LRRN6A is a novel gene of relevance in the molecular and cellular neurobiology of vertebrates. [source] Depressive Symptoms in Middle Age and the Development of Later-Life Functional Limitations: The Long-Term Effect of Depressive SymptomsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2010Kenneth E. Covinsky MD OBJECTIVES: To determine whether middle-aged persons with depressive symptoms are at higher risk for developing activity of daily living (ADL) and mobility limitations as they advance into older age than those without. DESIGN: Prospective cohort study. SETTING: The Health and Retirement Study (HRS), a nationally representative sample of people aged 50 to 61. PARTICIPANTS: Seven thousand two hundred seven community living participants in the 1992 wave of the HRS. MEASUREMENTS: Depressive symptoms were measured using the 11-item Center for Epidemiologic Studies Depression Scale (CES-D 11), with scores of 9 or more (out of 33) classified as significant depressive symptoms. Difficulty with five ADLs and basic mobility tasks (walking several blocks or up one flight of stairs) was measured every 2 years through 2006. The primary outcome was persistent difficulty with ADLs or mobility, defined as difficulty in two consecutive waves. RESULTS: Eight hundred eighty-seven (12%) subjects scored 9 or higher on the CES-D 11 and were classified as having significant depressive symptoms. Over 12 years of follow-up, subjects with depressive symptoms were more likely to reach the primary outcome measure of persistent difficulty with mobility or difficulty with ADL function (45% vs 23%, Cox hazard ratio (HR)=2.33, 95% confidence interval (CI)=2.06,2.63). After adjusting for age, sex, measures of socioeconomic status, comorbid conditions, high body mass index, smoking, exercise, difficulty jogging 1 mile, and difficulty climbing several flights of stairs, the risk was attenuated but still statistically significant (Cox HR=1.44, 95% CI=1.25,1.66). CONCLUSION: Depressive symptoms independently predict the development of persistent limitations in ADLs and mobility as middle-aged persons advance into later life. Middle-aged persons with depressive symptoms may be at greater risk for losing their functional independence as they age. [source] Cytokine stimulation and the choice of promoter are critical factors for the efficient transduction of mouse T cells with HIV-1 vectorsTHE JOURNAL OF GENE MEDICINE, Issue 2 2010David E. Gilham Abstract Background HIV-1 fails to successfully infect mouse T cells as a result of several blocks in the viral replication cycle. We investigated whether this also impacted on the use of HIV-1 derived lentiviral vectors for stable gene transfer into mouse T cells. Methods Freshly isolated primary mouse T cells were immediately mixed with lentiviral vectors encoding an enhanced green fluorescent protein marker gene and transduction frequency was determined after 5 days of culture. Results Optimal transduction required both mouse T cell activation and cytokine support. Furthermore, transduction was also dependent upon the promoter chosen, with the rank order of potency being PGK > EF1 > SFFV > CMV. HIV-1 lentiviral vectors also efficiently transduced cytokine-stimulated T cells (in the absence of antibody driven T cell activation), albeit with a lower level of transgene expression compared to fully-activated T cells. Conclusions The present study demonstrates that primary mouse T cells can be efficiently transduced with HIV-1 lentiviral vectors, opening up prospects for their use in mouse models of gene-modified adoptive cellular therapy. Copyright © 2009 John Wiley & Sons, Ltd. [source] Comparison of best,worst and hedonic scaling for the measurement of consumer wine preferencesAUSTRALIAN JOURNAL OF GRAPE AND WINE RESEARCH, Issue 3 2009S. MUELLER Abstract Background and Aims:, Best,worst scaling (BWS) is compared to standard hedonic scaling for measuring consumer wine preferences. BWS is a relatively new method for producing ratio-level scales and has gained recent attention for application in sensory research, but has not been applied to wine. Methods and Results:, Regular wine consumers (112) evaluated eight designed wines with both scaling methods in an intra-subject design over two test periods. The methods did not result in comparable product liking results. The eight wines could almost be differentiated on an aggregated level with hedonic ratings (P = 0.076); there was no significant difference with BWS. Latent class analysis was used to identify two clusters, which differed on the preferences for the designed sensory components. The BWS design had to be split into several blocks, so no complete individual measures were available, which prevented analysing heterogeneity for this method. Conclusions:, BWS needs more wines to be assessed per person in order to discriminate between red wines and to allow modelling of consumer preference heterogeneity. Respondents would have to accomplish complete individual BWS designs, which requires repeated exposure to the same set of wines over several tasting sessions. Significance of the Study:, This study demonstrates that BWS is not as suitable for sensory consumer preference measurement of red wine as hedonic rating. While BWS has shown a higher discriminative ability for different products and in non-sensory research, the factors of alcohol, tannin and memory fatigue make it less practical for red wine sensory measurement compared to hedonic rating. [source] |