Cryptococcus neoformans (Cn) is a deadly fungal pathogen whose intracellular lifestyle is important for virulence. Host mechanisms controlling fungal phagocytosis and replication remain obscure. Here, we perform a global phosphoproteomic analysis of the host response to Cryptococcus infection. Our analysis reveals numerous and diverse host proteins that are differentially phosphorylated following fungal ingestion by macrophages, thereby indicating global reprogramming of host kinase signaling. Notably, phagocytosis of the pathogen activates the host autophagy initiation complex (AIC) and the upstream regulatory components LKB1 and AMPKα, which regulate autophagy induction through their kinase activities. Deletion of Prkaa1, the gene encoding AMPKα1, in monocytes results in resistance to fungal colonization of mice. Finally, the recruitment of AIC components to nascent Cryptococcus-containing vacuoles (CnCVs) regulates the intracellular trafficking and replication of the pathogen. These findings demonstrate that host AIC regulatory networks confer susceptibility to infection and establish a proteomic resource for elucidating host mechanisms that regulate fungal intracellular parasitism. © 2017 Elsevier Inc.
الوصف Mixed ligand complexes of Cu (II), Co (II) and Zn (II) with 2-((4-(1-(4-chlorophenylimino) ethyl) phenylimino) methyl) phenol (L) and histidine (His) have been prepared and diagnosed by ¹H and13 C NMR, FT-IR and electronic spectral data, thermal gravimetric, molar conductance and metal analysis measurements. The ligand (L) shows a bidentate nature and the coordination occurs through N and O atoms of imine group and phenol group respectively whereas (His) behave as tridentate ligand, coordinating through the-NH2 group and carboxylate oxygen group and N atoms of imidazole ring. The analytical studies for three complexes have shown octahedral structure. The anticancer activity was screened against human cancer cell such Follicular
... Show MoreKarst aquifers in semi-arid regions are vital yet exceptionally vulnerable lifelines. This study investigates how tectonic, geomorphological, and climatic factors control the dynamics of karst springs in the El Menzel Causse (Middle Atlas, Morocco). Using an integrated approach that combines field investigations, remote sensing, and quantitative hydro-climatic analysis, we identify the mechanisms driving the system’s severe decline. Results indicated that the structural architecture of the major fault systems in the North Middle Atlas Fault (NMAF) and the Median Middle Atlas Fault (MMAF), governs the spatial distribution of more than 50 springs, which occur preferentially within highly permeable fault damage zones. However, the aquifer is
... Show MoreThe objective Effect of Internal and External Environment and its Psychological & Practical Reflection on the Political Decision-Making Process
Background: Dyslipidemia is defined as an abnormally high level of various lipids in the blood. It is considered a major risk for atherosclerosis and coronary artery disease. Genetic susceptibility can have a significant influence on the development and progression of dyslipidemia. ApoB-100 R3500Q mutation and ApoE variants are among those genetic risks for dyslipidemia. This study aims to assess the possible contribution of ApoB and ApoE variants on lipid profile among a group of early-onset ischemic heart disease (IHD) patients in comparison to a group of controls. Methods: Forty patients with dyslipidemia and early-onset IHD without chronic conditions likely to cause derangement of lipid levels were recruited to this case-control study
... Show MoreThe problem of the research is that there is a weakness in speed endurance, which has a direct impact on achievement, as it leads to early fatigue, lack of concentration, and a low level of effectiveness of performance, which made the researchers interested in this problem and finding solutions to it. Hence the importance of the research is evident: preparing cardiorespiratory fitness training to develop speed endurance and rate adaptation. The heartbeat that occurs in runners is a continuous result of training and the use of a type of training that suits the requirements of the 1500-meter running competition. The researchers used the experimental approach with pre- and post-testing for the experimental and control groups. The resea
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