Apolipoprotein C3 (APOC3) mutations carriers typically display high plasma high‐density lipoprotein cholesterol (HDL‐C) and low triglycerides (TGs). We set out to investigate the prevalence and ...clinical consequences of APOC3 mutations in individuals with hyperalphalipoproteinemia. Two novel mutations (c.‐13‐2A>G and c.55+1G>A) and one known mutation (c.127G>A;p.Ala43Thr) were found. Lipid profiles and apoCIII isoform distributions were measured. c.55+1G>A mutation carriers displayed higher HDL‐C percentiles (35.6 ± 35.8 vs 99.0 ± 0, p = 0.002) and lower TGs (0.51 (0.37–0.61) vs 1.42 (1.12–1.81) mmol/l, p = 0.007) and apoCIII levels (4.24 ± 1.57 vs 7.33 ± 3.61 mg/dl, p = 0.18). c.‐13‐2A>G mutation carriers did not display significantly different HDL‐C levels (84.0 ± 30.0 vs 63.7 ± 45.7, p = 0.50), a trend towards lower TGs 0.71 (0.54 to 0.78) vs 0.85 (0.85 to –) mmol/l, p = 0.06 and significantly lower apoCIII levels (3.09 ± 1.08 vs 11.45 ± 1.06 mg/dl, p = 0.003). p.Ala43Thr mutation carriers displayed a trend towards higher HDL‐C percentiles (91.2 ± 31.8 vs 41.0 ± 29.7 mmol/l, p = 0.06) and significantly lower TGs 0.58 (0.36–0.63) vs 0.95 (0.71–1.20) mmol/l, p = 0.02 and apoCIII levels (4.92 ± 2.33 vs 6.60 ± 1.60, p = 0.25). Heterozygosity for APOC3 mutations results in high HDL‐C and low TGs and apoCIII levels. This favourable lipid profile in patients with genetically low apoCIII levels holds promise for current studies investigating the potential of apoCIII inhibition as a novel therapeutic in cardiovascular disease prevention.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The extraordinary cellular heterogeneity of the mammalian nervous system has largely hindered the molecular analysis of neuronal identity and diversity. In order to uncover mechanisms involved in ...neuronal differentiation and diversification, we have monitored the expression profiles of individual neurons and progenitor cells collected from dissociated tissue or captured from intact slices. We demonstrate that this technique provides a sensitive and reproducible representation of the single-cell transcriptome. In the olfactory system, hundreds of transcriptional differences were identified between olfactory progenitors and mature sensory neurons, enabling us to define the large variety of signaling pathways expressed by individual progenitors at a precise developmental stage. Finally, we show that regional differences in gene expression can be predicted from transcriptional analysis of single neuronal precursors isolated by laser capture from defined areas of the developing brain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The 2020 World Happiness Report suggests that rural residents in Northern and Western Europe, North America, Australia and New Zealand are generally happier than their urban counterparts. Similar ...findings have been reported in country-level studies and broader regional research, especially in Europe. Such findings go against conventional wisdom in the field and represent something of a conundrum to researchers and policymakers alike: the rural–urban happiness paradox. Is quality of life really better in the countryside? How and under which circumstances is this the case? Did influential writers like Edward Glaeser get it all wrong when suggesting that the city had now triumphed? What can we learn from digging deeper in the rural–urban happiness paradox and which critical questions does this leave us with for the future? What might policymakers, planners, architects and other influential actors learn from such an exercise? The purpose of the proposed book is to delve deeper into these matters by asking what quality of life in rural areas is actually all about. Since 2018 a cross-disciplinary team of researchers from four research environments at three Danish universities has been carrying out an ambitious research project to do just that. In this edited volume their findings are presented alongside chapters written by specially commissioned international authors from across Europe, North America, Asia and Africa.
Mutagenic analyses have identified structural motifs important for TCR-mediated signaling in the antigen-binding chains, CD3 and zeta subunits of the TCR complex. In this study, we altered selected ...residues in the transmembrane and extracellular constant regions of the TCR beta chain and expressed the mutants in a T hybridoma line bearing endogenous receptor. We measured cytokine production and apoptosis in response to antigen or antibody. We found that mutation of one or both of the transmembrane tyrosine residues in the TCR beta chain caused a marked reduction in responsiveness. Mutation of the transmembrane serine to alanine also reduced responses, although less markedly. Immunoprecipitation analyses showed that the TCR beta mutations did not alter association with zeta. These experiments identify a signaling role for the transmembrane domain of the TCR beta chain.
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