Prenatal genotyping of Gaucher disease in Egypt

Objective: To use chorionic villi sampling (CVS) and amniocentesis to determine the genotyping of Gaucher Disease (GD) of fetuses of pregnant mothers who had a previous child affected by GD.Methods: The study was conducted between January 2009 and December 2012. It included 42 pregnant women that gave informed written consent. Thirty mothers presented early so they underwent CVS at 10–12 weeks of pregnancy while 12 mothers presented later and underwent amniocentesis at 14–16 weeks. Strip assay for the identification of Glucocerebrosidase (GBA) gene mutations in the samples of chrorionic villi and amniotic fluid was based on polymerase chain reaction (PCR) and reverse hybridization.Results: The age of the studied pregnant women ranged from 19 to 26 years. Consanguinity was present in 38 cases. Eighteen women were pregnant in affected fetuses. The results of genotyping revealed 15 cases were homozygous L444P/L444P and one case homozygous (N370s/N370s) while two cases were heterogeneous (L444P/D409H). Twenty-four pregnant women had carrier fetuses which were all heterozygous L444P.Conclusion: This study highlights the findings of an extended gene mutation examination for prenatal diagnosis of Guacher Disease. The study found out that the most common mutation was L444P/L444P.Keywords: Gaucher diseases; Prenatal diagnosis; Egypt; Gene; Mutatio

Cisplatin induces tolerogenic dendritic cells in response to TLR agonists via the abundant production of IL-10, thereby promoting Th2-and Tr1-biased T-cell immunity

Although many advantageous roles of cisplatin (cis-diamminedichloroplatinum (II), CDDP) have been reported in cancer therapy, the immunomodulatory roles of cisplatin in the phenotypic and functional alterations of dendritic cells (DCs) are poorly understood. Here, we investigated the effect of cisplatin on the functionality of DCs and the changes in signaling pathways activated upon toll-like receptor (TLR) stimulation. Cisplatin-treated DCs down-regulated the expression of cell surface molecules (CD80, CD86, MHC class I and II) and up-regulated endocytic capacity in a dose-dependent manner. Upon stimulation with various TLR agonists, cisplatin-treated DCs showed markedly increased IL-10 production through activation of the p38 MAPK and NF-kappa B signaling pathways without altering the levels of TNF-alpha and IL-12p70, indicating the cisplatin-mediated induction of tolerogenic DCs. This effect was dependent on the production of IL-10 from DCs, as neither DCs isolated from IL-10(-/-) mice nor IL-10-neutralized DCs generated tolerogenic DCs. Interestingly, DCs that were co-treated with cisplatin and lipopolysaccharide (LPS) exhibited a decreased immunostimulatory capacity for inducing the proliferation of Th1- and Th17-type T cells; instead, these DCs contributed to Th2-type T cell immunity. Furthermore, in vitro and in vivo investigations revealed a unique T cell population, IL-10-producing CD3(+)CD4(+)LAG-3(+)CD49b(+)CD25(-)Foxp3(-) Tr1 cells, that was significantly increased without altering the Foxp3(+) regulatory T cell population. Taken together, our results suggest that cisplatin induces immune-suppressive tolerogenic DCs in TLR agonist-induced inflammatory conditions via abundant IL-10 production, thereby skewing Th cell differentiation towards Th2 and Tr1 cells. This relationship may provide cancer cells with an opportunity to evade the immune system.1123Ysciescopu

Cisplatin induces tolerogenic dendritic cells in response to TLR agonists via the abundant production of IL-10, therby promoting Th2- and Tr1-biased T-cell immunity

Although many advantageous roles of cisplatin (cis-diamminedichloroplatinum (II), CDDP) have been reported in cancer therapy, the immunomodulatory roles of cisplatin in the phenotypic and functional alterations of dendritic cells (DCs) are poorly understood. Here, we investigated the effect of cisplatin on the functionality of DCs and the changes in signaling pathways activated upon toll-like receptor (TLR) stimulation. Cisplatin-treated DCs down-regulated the expression of cell surface molecules (CD80, CD86, MHC class I and II) and up-regulated endocytic capacity in a dose-dependent manner. Upon stimulation with various TLR agonists, cisplatintreated DCs showed markedly increased IL-10 production through activation of the p38 MAPK and NF-κB signaling pathways without altering the levels of TNF-α and IL- 12p70, indicating the cisplatin-mediated induction of tolerogenic DCs. This effect was dependent on the production of IL-10 from DCs, as neither DCs isolated from IL-10- /- mice nor IL-10-neutralized DCs generated tolerogenic DCs. Interestingly, DCs that were co-treated with cisplatin and lipopolysaccharide (LPS) exhibited a decreased immunostimulatory capacity for inducing the proliferation of Th1- and Th17-type T cells; instead, these DCs contributed to Th2-type T cell immunity. Furthermore, in vitro and in vivo investigations revealed a unique T cell population, IL-10-producing CD3+CD4+LAG-3+CD49b+CD25-Foxp3- Tr1 cells, that was significantly increased without altering the Foxp3+ regulatory T cell population. Taken together, our results suggest that cisplatin induces immune-suppressive tolerogenic DCs in TLR agonistinduced inflammatory conditions via abundant IL-10 production, thereby skewing Th cell differentiation towards Th2 and Tr1 cells. This relationship may provide cancer cells with an opportunity to evade the immune system.1231sciescopu

Wandering behaviour prevents inter and intra oceanic speciation in a coastal pelagic fish

Small pelagic fishes have the ability to disperse over long distances and may present complex evolutionary histories. Here, Old World Anchovies (OWA) were used as a model system to understand genetic patterns and connectivity of fish between the Atlantic and Pacific basins. We surveyed 16 locations worldwide using mtDNA and 8 microsatellite loci for genetic parameters, and mtDNA (cyt b; 16S) and nuclear (RAG1; RAG2) regions for dating major lineage-splitting events within Engraulidae family. The OWA genetic divergences (0-0.4%) are compatible with intra-specific divergence, showing evidence of both ancient and contemporary admixture between the Pacific and Atlantic populations, enhanced by high asymmetrical migration from the Pacific to the Atlantic. The estimated divergence between Atlantic and Pacific anchovies (0.67 [0.53-0.80] Ma) matches a severe drop of sea temperature during the Gunz glacial stage of the Pleistocene. Our results support an alternative evolutionary scenario for the OWA, suggesting a coastal migration along south Asia, Middle East and eastern Africa continental platforms, followed by the colonization of the Atlantic via the Cape of the Good Hope.Portuguese Foundation for Science & Technology (FCT) [SFRH/BD/36600/2007]; FCT [UID/MAR/04292/2013, SFRH/BPD/65830/2009]; FCT strategic plan [UID/Multi/04326/2013]info:eu-repo/semantics/publishedVersio

Benchmark Problems in Eddy-Current NDE

Inversion of eddy-current data and the reconstruction of flaws is the preeminent problem in electromagnetic nondestructive evaluation (NDE). This places a premium on developing good forward models for computing field-flaw interactions, because all inversion algorithms must, of necessity, rely on such calculations. There has evolved in recent years several sophisticated computational models for the forward problem [1–4], but these models differ significantly in their theoretical and numerical approaches. For example, [1-3] use a volume-integral approach that incorporates fast Fourier transforms with conjugate gradients to solve the resulting linear system of equations, whereas [4] uses finite-elements

Destabilization of the thermohaline circulation by transient perturbations to the hydrological cycle

We reconsider the problem of the stability of the thermohaline circulation as described by a two-dimensional Boussinesq model with mixed boundary conditions. We determine how the stability properties of the system depend on the intensity of the hydrological cycle. We define a two-dimensional parameters' space descriptive of the hydrology of the system and determine, by considering suitable quasi-static perturbations, a bounded region where multiple equilibria of the system are realized. We then focus on how the response of the system to finite-amplitude surface freshwater forcings depends on their rate of increase. We show that it is possible to define a robust separation between slow and fast regimes of forcing. Such separation is obtained by singling out an estimate of the critical growth rate for the anomalous forcing, which can be related to the characteristic advective time scale of the system.Comment: 37 pages, 8 figures, submitted to Clim. Dy

On acceleration of Krylov-subspace-based Newton and Arnoldi iterations for incompressible CFD: replacing time steppers and generation of initial guess

We propose two techniques aimed at improving the convergence rate of steady state and eigenvalue solvers preconditioned by the inverse Stokes operator and realized via time-stepping. First, we suggest a generalization of the Stokes operator so that the resulting preconditioner operator depends on several parameters and whose action preserves zero divergence and boundary conditions. The parameters can be tuned for each problem to speed up the convergence of a Krylov-subspace-based linear algebra solver. This operator can be inverted by the Uzawa-like algorithm, and does not need a time-stepping. Second, we propose to generate an initial guess of steady flow, leading eigenvalue and eigenvector using orthogonal projection on a divergence-free basis satisfying all boundary conditions. The approach, including the two proposed techniques, is illustrated on the solution of the linear stability problem for laterally heated square and cubic cavities

A universal model for mobility and migration patterns

Introduced in its contemporary form by George Kingsley Zipf in 1946, but with roots that go back to the work of Gaspard Monge in the 18th century, the gravity law is the prevailing framework to predict population movement, cargo shipping volume, inter-city phone calls, as well as bilateral trade flows between nations. Despite its widespread use, it relies on adjustable parameters that vary from region to region and suffers from known analytic inconsistencies. Here we introduce a stochastic process capturing local mobility decisions that helps us analytically derive commuting and mobility fluxes that require as input only information on the population distribution. The resulting radiation model predicts mobility patterns in good agreement with mobility and transport patterns observed in a wide range of phenomena, from long-term migration patterns to communication volume between different regions. Given its parameter-free nature, the model can be applied in areas where we lack previous mobility measurements, significantly improving the predictive accuracy of most of phenomena affected by mobility and transport processes.Comment: Main text and supplementary informatio