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

Low frequency split cycle cryocooler

A split cycle Stirling cryocooler with two different drive motors and operating at a low drive frequency can have high thermodynamic efficiency. The temperature of the cold end of the cryocooler varies with drive frequency, voltage of the input electrical power and initial charge pressure values. The cryocooler operating at 8 Hz can provide 7 watts of refrigeration at 77 K for 230 watts of electrical input power

A comparison of the local spiral structure from Gaia DR2 and VLBI maser parallaxes

Context. The Gaia mission has released the second data set (Gaia DR2), which contains parallaxes and proper motions for a large number of massive, young stars. Aims. We investigate the spiral structure in the solar neighborhood revealed by Gaia DR2 and compare it with that depicted by VLBI maser parallaxes. Methods. We examined three samples with different constraints on parallax uncertainty and distance errors and stellar spectral types: (1) all OB stars with parallax errors of less than 10%; (2) only O-type stars with 0.1 mas errors imposed and with parallax distance errors of less than 0.2 kpc; and (3) only O-type stars with 0.05 mas errors imposed and with parallax distance errors of less than 0.3 kpc. Results. In spite of the significant distance uncertainties for stars in DR2 beyond 1.4 kpc, the spiral structure in the solar neighborhood demonstrated by Gaia agrees well with that illustrated by VLBI maser results. The O-type stars available from DR2 extend the spiral arm models determined from VLBI maser parallaxes into the fourth Galactic quadrant, and suggest the existence of a new spur between the Local and Sagittarius arms.Comment: 4 pages, 3 figures, 1 table, accepted for publication in A&

Extracting the phase information from atomic memory by intensity correlation measurement

We demonstrate experimentally controlled storage and retrieval of the optical phase information in a higher-order interference scheme based on Raman process in 87Rb atomic vapor cells. An interference pattern is observed in intensity correlation measurement between the write Stokes field and the delayed read Stokes field as the phase of the Raman write field is scanned. This result implies that the phase information of the Raman write field can be written into the atomic spin wave via Raman process in a high gain regime and subsequently read out via a spin-wave enhanced Raman process, thus achieving optical storage of phase information. This technique should find applications in optical phase image storage, holography and information processing

Excessive Activation of TGFβ by Spinal Instability Causes Vertebral Endplate Sclerosis

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miR-9 and miR-124 synergistically affect regulation of dendritic branching via the AKT/GSK3β pathway by targeting Rap2a

A single microRNA (miRNA) can regulate expression of multiple proteins, and expression of an individual protein may be controlled by numerous miRNAs. This regulatory pattern strongly suggests that synergistic effects of miRNAs play critical roles in regulating biological processes. miR-9 and miR-124, two of the most abundant miRNAs in the mammalian nervous system, have important functions in neuronal development. In this study, we identified the small GTP-binding protein Rap2a as a common target of both miR-9 and miR-124. miR-9 and miR-124 together, but neither miRNA alone, strongly suppressed Rap2a, thereby promoting neuronal differentiation of neural stem cells (NSCs) and dendritic branching of differentiated neurons. Rap2a also diminished the dendritic complexity of mature neurons by decreasing the levels of pAKT and pGSK3β. Our results reveal a novel pathway in which miR-9 and miR-124 synergistically repress expression of Rap2a to sustain homeostatic dendritic complexity during neuronal development and maturation

Coordination of PSSs and SVC damping controller to improve probabilistic small-signal stability of power system with wind farm integration

A modified fruit fly optimization algorithm (MFOA) combined with a probabilistic approach are proposed in this paper to coordinate and optimize the parameters of power system stabilizers (PSSs) and static VAR compensator (SVC) damping controller for improving the probabilistic small-signal stability of power systems with large-scale wind generation, taking into consideration the stochastic uncertainty of system operating conditions. It is generally accepted that there is a threat to the stability of power system with penetration of wind farm. In addition, the stochastic fluctuations of wind generation make PSSs tuning more difficult. In this paper, PSSs and SVC damping controller are employed for suppressing local and inter-area low frequency oscillation. In order to eliminate the adverse effect between PSSs and SVC damping controller, the MFOA based on the probabilistic eigenvalue is applied to coordinate and optimize their parameters. The effectiveness of the proposed approach is verified on two test systems