Subseasonal variability associated with Asian summer monsoon simulated by 14 IPCC AR4 coupled GCMs

This study evaluates the subseasonal variability associated with the Asian summer monsoon in 14 coupled general circulation models (GCMs) participating in the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4). Eight years of each model's twentieth-century climate simulation are analyzed. The authors focus on the three major components of Asian summer monsoon: the Indian summer monsoon (ISM), the western North Pacific summer monsoon (WNPSM), and the East Asian summer monsoon (EASM), together with the two dominant subseasonal modes: the eastward- and northward-propagating boreal summer intraseasonal oscillation (BSIO) and the westward-propagating 12-24-day mode. The results show that current state-of-the-art GCMs still have difficulties and display a wide range of skill in simulating the subseasonal variability associated with Asian summer monsoon. During boreal summer (May-October), most of the models produce reasonable seasonal-mean precipitation over the ISM region, but excessive precipitation over the WNPSM region and insufficient precipitation over the EASM region. In other words, models concentrate their rain too close to the equator in the western Pacific. Most of the models simulate overly weak total subseasonal (2-128 day) variance, as well as too little variance for BSIO and the 12-24-day mode. Only 4-5 models produce spectral peaks in the BSIO and 12-24-day frequency bands; instead, most of the models display too red a spectrum, that is, an overly strong persistence of precipitation. For the seven models with three-dimensional data available, five reproduce the preconditioning of moisture in BSIO but often with a too late starting time, and only three simulate the phase lead of low-level convergence. Interestingly, although models often have difficulty in simulating the eastward propagation of BSIO, they tend to simulate well the northward propagation of BSIO, together with the westward propagation of the 12-24-day mode. The northward propagation in these models is thus not simply a NW-SE-tilted tail protruding off of an eastward-moving deep-tropical intraseasonal oscillation.open444

Structural and biochemical characterization of the KLHL3-WNK kinase interaction important in blood pressure regulation

WNK1 [with no lysine (K)] and WNK4 regulate blood pressure by controlling the activity of ion co-transporters in the kidney. Groundbreaking work has revealed that the ubiquitylation and hence levels of WNK isoforms are controlled by a Cullin-RING E3 ubiquitin ligase complex (CRL3KLHL3) that utilizes CUL3 (Cullin3) and its substrate adaptor, KLHL3 (Kelch-like protein 3). Loss-of-function mutations in either CUL3 or KLHL3 cause the hereditary high blood pressure disease Gordon's syndrome by stabilizing WNK isoforms. KLHL3 binds to a highly conserved degron motif located within the C-terminal non-catalytic domain of WNK isoforms. This interaction is essential for ubiquitylation by CRL3KLHL3 and disease-causing mutations in WNK4 and KLHL3 exert their effects on blood pressure by disrupting this interaction. In the present study, we report on the crystal structure of the KLHL3 Kelch domain in complex with the WNK4 degron motif. This reveals an intricate web of interactions between conserved residues on the surface of the Kelch domain β-propeller and the WNK4 degron motif. Importantly, many of the disease-causing mutations inhibit binding by disrupting critical interface contacts. We also present the structure of the WNK4 degron motif in complex with KLHL2 that has also been reported to bind WNK4. This confirms that KLHL2 interacts with WNK kinases in a similar manner to KLHL3, but strikingly different to how another KLHL protein, KEAP1 (Kelch-like enoyl-CoA hydratase-associated protein 1), binds to its substrate NRF2 (nuclear factor-erythroid 2-related factor 2). The present study provides further insights into how Kelch-like adaptor proteins recognize their substrates and provides a structural basis for how mutations in WNK4 and KLHL3 lead to hypertension

In situ annealing of superconducting MgB2 films prepared by pulsed laser deposition

The in situ annealing conditions of pulsed laser deposited MgB2 films were studied. The precursor films were deposited at 250 C from a stoichiometric MgB2 target in a 120mTorr Ar atmosphere. The films were then in situ annealed at a temperature from 450 C to 800 C and an annealing time from 1 minute to 10 minutes. We found that the superconducting properties depend in a crucial way on the annealing conditions: temperature, heating rate and time. The best film with a thickness of ~600nm was obtained under the following annealing conditions: Tanneal=680-690 C, tanneal=1 min, heating rate= 38 C/min. The Tc onset of the film is 28K with a transition width of ~10K. The hysteresis loop of magnetic moment of the film indicates weak field dependence in high fields. Magneto-optical imaging of the film showed quite homogeneous magnetic flux penetration, indicating structural homogeneity. The films without annealing showed no superconductivity.Comment: 12 pages, 6 figure

Modulation of RANTES expression by HCV core protein in liver derived cell lines

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) infection is associated with high percentage of chronicity which implies the ability of the virus to evade or modulate host cell immune system. Modulation of chemokines, such as RANTES may be part of the virus induced pathogenicity. We examined the effect of core and structural proteins of HCV on RANTES expression in two liver derived cell lines, HepG2 and Chang Liver (CHL).</p> <p>Methods</p> <p>HepG2 and Chang Liver (CHL) cell lines were established and selected for constitutive expression of HCV core and structural genes. Flow cytometry and quantitative RT-PCR analysis were performed to examine the effect of HCV core protein on RANTES expression. Luciferase analysis after RANTES-Luc-promoter transfection of established cell lines was assayed by luminometer measurements (RLU) of RANTES promoter activity. IRF-1 and IRF-7 expression was then examined by immunoblotting analysis.</p> <p>Results</p> <p>Results of flow cytometry and RT-PCR analysis indicated that RANTES is differentially regulated by HCV core protein in the two cell lines examined as its expression was inhibited in HepG2 cells, by a reduction of RANTES promoter activity. Conversely, RANTES protein and mRNA were induced by the core protein in CHL cells, through the induction of the promoter.</p> <p>Since HCV genome modulates IRF-1 and IRF-7 in replicon system and IRF-1, IRF-3 and IRF-7 have been reported to regulate RANTES promoter in various cell systems, analysis of the mechanism underlying RANTES modulation by the core protein revealed that IRF-1 expression was induced in HepG2 cells by the core protein, whereas in CHL cells it was expressed at a very low level that was not influenced by transfection with the core protein construct. This suggested that IRF-1 level may mediate the expression of RANTES in cell lines of liver origin. The effect of the core protein on RANTES promoter was countered by co-transfection with NF90, a double-stranded-RNA binding protein that activates some interferon response genes and acts as a component of cell defense against viral infection.</p> <p>Conclusion</p> <p>HCV core protein have opposite effects on the expression of RANTES in different cell types <it>in vitro</it>, possibly reflecting a similar scenario in different microenvironments <it>in vivo</it>.</p

A Lipopeptide Facilitate Induction of Mycobacterium leprae Killing in Host Cells

Little is known of the direct microbicidal activity of T cells in leprosy, so a lipopeptide consisting of the N-terminal 13 amino acids lipopeptide (LipoK) of a 33-kD lipoprotein of Mycobacterium leprae, was synthesized. LipoK activated M. leprae infected human dendritic cells (DCs) to induce the production of IL-12. These activated DCs stimulated autologous CD4+ or CD8+ T cells towards type 1 immune response by inducing interferon-gamma secretion. T cell proliferation was also evident from the CFSE labeling of target CD4+ or CD8+ T cells. The direct microbicidal activity of T cells in the control of M. leprae multiplication is not well understood. The present study showed significant production of granulysin, granzyme B and perforin from these activated CD4+ and CD8+ T cells when stimulated with LipoK activated, M. leprae infected DCs. Assessment of the viability of M. leprae in DCs indicated LipoK mediated T cell-dependent killing of M. leprae. Remarkably, granulysin as well as granzyme B could directly kill M. leprae in vitro. Our results provide evidence that LipoK could facilitate M. leprae killing through the production of effector molecules granulysin and granzyme B in T cells