Knockdown of zebrafish Nav1.6 sodium channel impairs embryonic locomotor activities

[[abstract]]Although multiple subtypes of sodium channels are expressed in most neurons, the specific contributions of the individual sodium channels remain to be studied. The role of zebrafish Nav1.6 sodium channels in the embryonic locomotor movements has been investigated by the antisense morpholino (MO) knockdown. MO1 and MO2 are targeted at the regions surrounding the translation start site of zebrafish Nav1.6 mRNA. MO3 is targeted at the RNA splicing donor site of exon 2. The correctly spliced Nav1.6 mRNA of MO3 morphants is 6% relative to that of the wild-type embryos. Nav1.6-targeted MO1, MO2 and MO3 attenuate the spontaneous contraction, tactile sensitivity, and swimming in comparison with a scrambled morpholino and mutated MO3 morpholino. No significant defect is observed in the development of slow muscles, the axonal projection of primary motoneurons, and neuromuscular junctions. The movement impairments caused by MO1, MO2, and MO3 suggest that the function of Nav1.6 sodium channels is essential on the normal early embryonic locomotor activities.[[notice]]補正完畢[[journaltype]]國

Measurements of the qsq dependence of the D0 to K mu nu and D0 to pi mu nu form factors

Using a large sample of D0 to K mu nu and pi mu nu decays collected by the FOCUS photoproduction experiment at Fermilab, we present new measurements of the q^2 dependence for the f+(q^2) form factor. These measured f+(q^2) form factors are fit to common parameterizations such as the pole dominance form and compared to recent unquenched Lattice QCD calculations. We find m_pole = 1.93+-0.05+-0.03 GeV/c^2 for D0 to K mu nu and m_pole = 1.91+0.30-0.15+-0.07 GeV/c^2 for D0 to pi mu nu and f-^{K}(0)/f+^{K}(0) = -1.7+1.5-1.4+-0.3.Comment: 14 pages, 6 figure

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

A first tentative Holocene sea-level curve for Singapore

Journal of Coastal Research141308-314JCRS

Performance of vertical flow constructed wetlands for faecal sludge drying bed leachate: Effect of hydraulic loading

The discharge of raw faecal sludge directly into the environment is a common practice that threatens environmental and public health in low-income countries. Planted drying beds are a promising and low-cost option for treatment of faecal sludge and the production of fodder plants, but current research shows the leachate quality does not meet guidelines for discharge. This paper investigates the use of Vertical Flow Constructed Wetlands (VFCWs) planted with Echinochloa pyramidalis for polishing of leachate from faecal sludge drying beds. At a pilot-scale, three hydraulic loads (50, 100 and 150 mm/d) were applied with single loadings once a week on VFCWs (corresponding to 31 ± 9, 63 ± 19, 94 ± 28 g/m2/month of BOD5; 21 ± 6, 42 ± 12, 63 ± 19 TKN; and 2 ± 1; 4 ± 4; 6 ± 6 PO4–P, respectively, for hydraulic loading rates of 50, 100 and 150 mm/d). Infiltration flow rate, plant growth, rhizospheric bacteria, and leachate characteristics were monitored. VFCWs were effective in reducing on average more than 80% of the pollutants monitored (COD, BOD5, NH4–N, TKN, PO4–P, and faecal bioindicators), which met all National Cameroon and WHO guidelines for safe reuse in agriculture, except for total nitrogen and faecal indicators. Results confirmed a correlation between plant density and rhizospheric bacteria growth with increasing hydraulic load. These are important results, demonstrating that VFCWs can operate efficiently at multiple hydraulic loadings, and are hence adaptable to different sized treatment schemes. It also illustrates that if plant production for fodder is a goal, increased loading rates are preferable as they achieve overall treatment goals and result in greater plant production