Whole exome sequencing reveals novel COL4A3 and COL4A4 mutations and resolves diagnosis in Chinese families with kidney disease.

Collagen IV-related nephropathies, including thin basement membrane nephropathy and Alport Syndrome (AS), are caused by defects in the genes COL4A3, COL4A4 and COL4A5. Diagnosis of these conditions can be hindered by variable penetrance and the presence of non-specific clinical or pathological features

First identification of PODXL nonsense mutations in autosomal dominant focal segmental glomerulosclerosis

Recently, a novel heterozygous missense mutation c.T1421G (p. L474R) in the PODXL gene encoding podocalyxin, was identified in an autosomal dominant focal segmental glomerulosclerosis (AD-FSGS) pedigree. However, this PODXL mutation appeared not to impair podocalyxin function and it is necessary to identify new PODXL mutations and determine their causative role for FSGS. In this study, we report the identification of a heterozygous nonsense PODXL mutations (Arg326X) in a Chinese pedigree featured by proteinuria and renal insufficiency with AD inheritance by whole exome sequencing (WES). Total mRNA and PODXL protein abundance were decreased in available peripheral blood cell samples of two affected patients undergoing hemodialysis, compared to those in healthy controls and hemodialysis controls without PODXL mutation. We identified another novel PODXL heterozygous nonsense mutation (c.C1133G; p.Ser378X) in a British-Indian pedigree of AD-FSGS by WES. In vitro study showed that, human embryonic kidney (HEK) 293T cells transfected with the pEGFP-PODXL-Arg326X or pEGFP-PODXL-Ser378X plasmid expressed significantly lower mRNA and PODXL protein compared to cells transfected with the wild-type plasmid. Blocking nonsense-mediated mRNA decay (NMD) significantly restored the amount of mutant mRNA and PODXL proteins, which indicated that the pathogenic effect of PODXL nonsense mutations is likely due to NMD, resulting in podocalyxin deficiency. Functional consequences caused by the PODXL nonsense mutations were inferred by siRNA knockdown in cultured podocytes and podocalyxin downregulation by siRNA resulted in decreased RhoA and ezrin activities, cell migration and stress fiber formation. Our results provided new data implicating heterozygous PODXL nonsense mutations in the development of FSGS

Insights into the Anaerobic Biodegradation Pathway of n-Alkanes in Oil Reservoirs by Detection of Signature Metabolites

published_or_final_versio

Understanding AGN-Host Connection in Partially Obscured Active Galactic Nuclei. Part I: The Nature of AGN+HII Composites

The goal of our serial papers is to examine the evolutionary connection between AGN and star formation in its host galaxy in the partially obscured AGNs (i.e., Seyfert 1.8 and 1.9 galaxies). Taking advantage of these galaxies, the properties of both components can be studied together by direct measurements. In this paper, we focus on the broad-line composite galaxies (composite AGNs) which are located between the theoretical and empirical separation lines in the [NII]/Ha vs. [OIII]/Hb diagram. These galaxies are searched for from the composite galaxies provided by the SDSS DR4 MPA/JHU catalogs. After re-analyze the spectra, we perform a fine classification for the 85 composite AGNs in terms of the BPT diagrams. All the objects located below the three theoretical separation lines are associated with a young stellar population (<1Gyrs), while either a young or old stellar population is identified in the individual multiply-classified object. The multiply-classified objects with a very old stellar population are located in the LINER region in the [OI]/Ha vs. [OIII]/Hb diagram. We then consider the connection between AGN and star formation to derive the key results. The Eddington ratio inferred from the broad Ha emission, the age of the stellar population of AGN's host as assessed by D_n(4000), and the line ratio [OI]/Ha are found to be related with each other. These relations strongly support the evolutionary scenario in which AGNs evolve from high L/L_Edd state with soft spectrum to low L/L_Edd state with hard spectrum as young stellar population ages and fades. The significant correlation between the line ratio [OI]/Ha and D_n(4000) leads us to suggest that the line ratio could be used to trace the age of stellar population in type I AGNs.Comment: 39 pages, 11 figures, 1 table, accepted by Ap

Search for D to phi l nu and measurement of the branching fraction for D to phi pi

Using a data sample of integrated luminosity of about 33 pb$^{-1}$ collected around 3.773 GeV with the BESII detector at the BEPC collider, the semileptonic decays $D^+ \to \phi e ^+\nu_e$, $D^+ \to \phi \mu^+\nu_\mu$ and the hadronic decay $D^+ \to \phi \pi^+$ are studied. The upper limits of the branching fractions are set to be $BF(D^+ \to \phi e ^+\nu_e) <$ 2.01% and $BF(D^+ \to \phi \mu^+ \nu_\mu) <$ 2.04% at the 90% confidence level. The ratio of the branching fractions for $D^+ \to \phi \pi^+$ relative to $D^+ \to K^-\pi^+\pi^+$ is measured to be $0.057 \pm 0.011 \pm 0.003$. In addition, the branching fraction for $D^+ \to \phi \pi^+$ is obtained to be $(5.2 \pm 1.0 \pm 0.4) \times 10^{-3}$.Comment: 6 pages, 5 figures, to be published in Eur.Phys.J.

Measurements of branching fractions for inclusive K0~/K0 and K*(892)+- decays of neutral and charged D mesons

Using the data sample of about 33 pb-1 collected at and around 3.773 GeV with the BES-II detector at the BEPC collider, we have studied inclusive K0~/K0 and K*(892)+- decays of D0 and D+ mesons. The branching fractions for the inclusive K0~/K0 and K*(892)- decays are measured to be BF(D0 to K0~/K0 X)=(47.6+-4.8+-3.0)%, BF(D+ to K0~/K0 X)=(60.5+-5.5+-3.3)%, BF(D0 to K*- X)=(15.3+- 8.3+- 1.9)% and BF(D+ to K*- X)=(5.7+- 5.2+- 0.7)%. The upper limits of the branching fractions for the inclusive K*(892)+ decays are set to be BF(D0 to K*+ X)<3.6% and BF(D+ to K*+ X) <20.3% at 90% confidence level

Measurement of the branching fractions of psi(2S) -> 3(pi+pi-) and J/psi -> 2(pi+pi-)

Using data samples collected at sqrt(s) = 3.686GeV and 3.650GeV by the BESII detector at the BEPC, the branching fraction of psi(2S) -> 3(pi+pi-) is measured to be [4.83 +- 0.38(stat) +- 0.69(syst)] x 10^-4, and the relative branching fraction of J/psi -> 2(pi+pi-) to that of J/psi -> mu+mu- is measured to be [5.86 +- 0.19(stat) +- 0.39(syst)]% via psi(2S) -> (pi+pi-)J/psi, J/psi -> 2(pi+pi-). The electromagnetic form factor of 3(pi+pi-) is determined to be 0.21 +- 0.02 and 0.20 +- 0.01 at sqrt(s) = 3.686GeV and 3.650GeV, respectively.Comment: 17pages, 7 figures, submitted to Phys. Rev.