LHCGR (luteinizing hormone/choriogonadotropin receptor)

Review on LHCGR (luteinizing hormone/choriogonadotropin receptor), with data on DNA, on the protein encoded, and where the gene is implicated

Survivin a radiogenetic promoter for glioblastoma viral gene therapy independently from CArG motifs

BACKGROUND: Radiogenetic therapy is a novel approach in the treatment of cancer, which employs genetic modification to alter the sensitivity of tumor cells to the effect of applied radiation. AIM: To select a potent radiation inducible promoter in the context of brain tumors and to investigate if CArG radio responsive motifs or other elements in the promoter nucleotide sequences can correlate to its response to radiation. METHODS: To select initial candidates for promoter inducible elements, the levels of mRNA expression of six different promoters were assessed using Quantitative RTPCR in D54 MG cells before and after radiation exposure. Recombinant Ad/reporter genes driven by five different promoters; CMV, VEGF, FLT-1, DR5 and survivin were constructed. Glioma cell lines were infected with different multiplicity of infection of the (promoter) Ad or CMV Ad. Cells were then exposed to a range of radiation (0–12 Gy) at single fraction. Fluorescent microscopy, Luc assay and X-gal staining was used to detect the level of expression of related genes. Different glioma cell lines and normal astrocytes were infected with Ad survivin and exposed to radiation. The promoters were analyzed for presence of CArG radio-responsive motifs and CCAAT box consensus using NCBI blast bioinformatics software. RESULTS: Radiotherapy increases the expression of gene expression by 1.25–2.5 fold in different promoters other than survivin after 2 h of radiation. RNA analysis was done and has shown an increase in copy number of tenfold for survivin. Most importantly cells treated with RT and Ad Luc driven by survivin promoter showed a fivefold increase in expression after 2 Gy of radiation in comparison to non-irradiated cells. Presence or absence of CArG motifs did not correlate with promoter response to radiation. Survivin with the best response to radiation had the lowest number of CCAAT box. CONCLUSION: Survivin is a selective potent radiation inducible promoter for glioblastoma viral gene therapy and this response to radiation could be independent of CArG motifs

A parameter-free total Lagrangian smooth particle hydrodynamics algorithm applied to problems with free surfaces

This paper presents a new Smooth Particle Hydrodynamics computational framework for the solution of inviscid free surface flow problems. The formulation is based on the Total Lagrangian description of a system of first-order conservation laws written in terms of the linear momentum and the Jacobian of the deformation. One of the aims of this paper is to explore the use of Total Lagrangian description in the case of large deformations but without topological changes. In this case, the evaluation of spatial integrals is carried out with respect to the initial undeformed configuration, yielding an extremely efficient formulation where the need for continuous particle neighbouring search is completely circumvented. To guarantee stability from the SPH discretisation point of view, consistently derived Riemann-based numerical dissipation is suitably introduced where global numerical entropy production is demonstrated via a novel technique in terms of the time rate of the Hamiltonian of the system. Since the kernel derivatives presented in this work are fixed in the reference configuration, the non-physical clumping mechanism is completely removed. To fulfil conservation of the global angular momentum, a posteriori (least-squares) projection procedure is introduced. Finally, a wide spectrum of dedicated prototype problems is thoroughly examined. Through these tests, the SPH methodology overcomes by construction a number of persistent numerical drawbacks (e.g. hour-glassing, pressure instability, global conservation and/or completeness issues) commonly found in SPH literature, without resorting to the use of any ad-hoc user-defined artificial stabilisation parameters. Crucially, the overall SPH algorithm yields equal second order of convergence for both velocities and pressure

Structural diversity in alkali metal and alkali metal magnesiate chemistry of the bulky 2,6-diisopropyl-N-(trimethylsilyl)anilino ligand

Bulky amido ligands are precious in s-block chemistry since they can implant complementary strong basic and weak nucleophilic properties within compounds. Recent work has shown the pivotal importance of the base structure with enhancement of basicity and extraordinary regioselectivities possible for cyclic alkali metal magnesiates containing mixed n-butyl/amido ligand sets. This work advances alkali metal and alkali metal magnesiate chemistry of the bulky aryl-silyl amido ligand [N(SiMe3)(Dipp)] (Dipp = 2,6-iPr2-C6H3). Infinite chain structures of the parent sodium and potassium amides are disclosed, adding to the few known crystallographically characterised unsolvated s-block metal amides. Solvation by PMDETA or TMEDA gives molecular variants of the lithium and sodium amides; whereas for potassium, PMDETA gives a molecular structure but TMEDA affords a novel, hemi-solvated infinite chain. Crystal structures of the first magnesiate examples of this amide in [MMg{N(SiMe3)(Dipp)}2(μ-nBu)]∞ (M = Na or K), are also revealed though these breakdown to their homometallic components in donor solvent as revealed through NMR and DOSY studies

The RNA Binding Protein SAM68 Transiently Localizes in the Chromatoid Body of Male Germ Cells and Influences Expression of Select MicroRNAs

The chromatoid body (CB) is a unique structure of male germ cells composed of thin filaments that condense into a perinuclear organelle after meiosis. Due to the presence of proteins involved in different steps of RNA metabolism and of different classes of RNAs, including microRNAs (miRNAs), the CB has been recently suggested to function as an RNA processing centre. Herein, we show that the RNA binding protein SAM68 transiently localizes in the CB, in concomitance with the meiotic divisions of mouse spermatocytes. Precise staging of the seminiferous tubules and co-localization studies with MVH and MILI, two well recognized CB markers, documented that SAM68 transiently associates with the CB in secondary spermatocytes and early round spermatids. Furthermore, although SAM68 co-immunoprecipitated with MVH in secondary spermatocytes, its ablation did not affect the proper localization of MVH in the CB. On the other hand, ablation of the CB constitutive component MIWI did not impair association of SAM68 with the CB. Isolation of CBs from Sam68 wild type and knockout mouse testes and comparison of their protein content by mass spectrometry indicated that Sam68 ablation did not cause overall alterations in the CB proteome. Lastly, we found that SAM68 interacts with DROSHA and DICER in secondary spermatocytes and early round spermatids and that a subset of miRNAs were altered in Sam68−/−germ cells. These results suggest a novel role for SAM68 in the miRNA pathway during spermatogenesis

Myeloid Heme Oxygenase-1 Haploinsufficiency Reduces High Fat Diet-Induced Insulin Resistance by Affecting Adipose Macrophage Infiltration in Mice

Increased adipose tissue macrophages contribute to obesity-induced metabolic syndrome. Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with potent anti-inflammatory and proangiogenic activities in macrophages. However, the role of macrophage HO-1 on obesity-induced adipose inflammation and metabolic syndrome remains unclear. Here we show that high-fat diet (HFD) feeding in C57BL/6J mice induced HO-1 expression in the visceral adipose tissue, particularly the stromal vascular fraction. When the irradiated C57BL/6J mice reconstituted with wild-type or HO-1+/− bone marrow were fed with HFD for over 24 weeks, the HO-1+/− chimeras were protected from HFD-induced insulin resistance and this was associated with reduced adipose macrophage infiltration and angiogenesis, suggesting that HO-1 affects myeloid cell migration toward adipose tissue during obesity. In vivo and in vitro migration assays revealed that HO-1+/− macrophages exhibited an impaired migration response. Chemoattractant-induced phosphorylation of p38 and focal adhesion kinase (FAK) declined faster in HO-1+/− macrophages. Further experiments demonstrated that carbon monoxide and bilirubin, the byproducts derived from heme degradation by HO-1, enhanced macrophage migration by increasing phosphorylation of p38 and FAK, respectively. These data disclose a novel role of hematopoietic cell HO-1 in promoting adipose macrophage infiltration and the development of insulin resistance during obesity

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Comparative Structural Analysis of Human DEAD-Box RNA Helicases

DEAD-box RNA helicases play various, often critical, roles in all processes where RNAs are involved. Members of this family of proteins are linked to human disease, including cancer and viral infections. DEAD-box proteins contain two conserved domains that both contribute to RNA and ATP binding. Despite recent advances the molecular details of how these enzymes convert chemical energy into RNA remodeling is unknown. We present crystal structures of the isolated DEAD-domains of human DDX2A/eIF4A1, DDX2B/eIF4A2, DDX5, DDX10/DBP4, DDX18/myc-regulated DEAD-box protein, DDX20, DDX47, DDX52/ROK1, and DDX53/CAGE, and of the helicase domains of DDX25 and DDX41. Together with prior knowledge this enables a family-wide comparative structural analysis. We propose a general mechanism for opening of the RNA binding site. This analysis also provides insights into the diversity of DExD/H- proteins, with implications for understanding the functions of individual family members