Class II ADP-ribosylation factors are required for efficient secretion of Dengue viruses

This article is available open access through the publisher’s website.Identification and characterization of virus-host interactions are very important steps toward a better understanding of the molecular mechanisms responsible for disease progression and pathogenesis. To date, very few cellular factors involved in the life cycle of flaviviruses, which are important human pathogens, have been described. In this study, we demonstrate a crucial role for class II Arf proteins (Arf4 and Arf5) in the dengue flavivirus life cycle. We show that simultaneous depletion of Arf4 and Arf5 blocks recombinant subviral particle secretion for all four dengue serotypes. Immunostaining analysis suggests that class II Arf proteins are required at an early pre-Golgi step for dengue virus secretion. Using a horseradish peroxidase protein fused to a signal peptide, we show that class II Arfs act specifically on dengue virus secretion without altering the secretion of proteins through the constitutive secretory pathway. Co-immunoprecipitation data demonstrate that the dengue prM glycoprotein interacts with class II Arf proteins but not through its C-terminal VXPX motif. Finally, experiments performed with replication-competent dengue and yellow fever viruses demonstrate that the depletion of class II Arfs inhibits virus secretion, thus confirming their implication in the virus life cycle, although data obtained with West Nile virus pointed out the differences in virus-host interactions among flaviviruses. Our findings shed new light on a molecular mechanism used by dengue viruses during the late stages of the life cycle and demonstrate a novel function for class II Arf proteins.Research Fund for Control of Infectious Diseases of Hong Kong and BNP Paribas Corporate and Investment Banking

DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics

The spatiotemporal proteome of the intervertebral disc (IVD) underpins its integrity and function. We present DIPPER, a deep and comprehensive IVD proteomic resource comprising 94 genome-wide profiles from 17 individuals. To begin with, protein modules defining key directional trends spanning the lateral and anteroposterior axes were derived from high-resolution spatial proteomes of intact young cadaveric lumbar IVDs. They revealed novel region-specific profiles of regulatory activities and displayed potential paths of deconstruction in the level- and location-matched aged cadaveric discs. Machine learning methods predicted a 'hydration matrisome' that connects extracellular matrix with MRI intensity. Importantly, the static proteome used as point-references can be integrated with dynamic proteome (SILAC/degradome) and transcriptome data from multiple clinical samples, enhancing robustness and clinical relevance. The data, findings, and methodology, available on a web interface (http://www.sbms.hku.hk/dclab/DIPPER/), will be valuable references in the field of IVD biology and proteomic analytics

Composite Membranes Containing Nanoparticles of Inorganic Ion Exchangers for Electrodialytic Desalination of Glycerol

Abstract Composite membranes were obtained by modification of heterogeneous polymer cation and anion-exchange membranes with nanoparticles of zirconium hydrophosphate and hydrated zirconium dioxide, respectively. The ion-exchange materials were investigated with the methods of electron microscopy, potentiometry, voltammetry, and impedance spectroscopy. Single nanoparticles, which were precipitated in aqueous media, form aggregates, when the composites are in a contact with polar organic solvent. Both single nanoparticles (up to 10 nm) and their aggregates (up to 200 nm) were precipitated in ion-exchange polymers in glycerol media. Non-aggregated nanoparticles improve electrical conductivity of the ion-exchange materials, the aggregates are barriers against fouling. The membranes were applied to NaCl removal from highly concentrated glycerine-water mixture containing organic additives (byproduct of biodiesel production). As opposite to pristine materials, the composites demonstrate stability against fouling

Association between atopy and recurrent vaginal candidiasis

To determine whether there is an association between atopy and recurrent vaginal candidiasis (RVC) and to evaluate the type-2 immune response in patients with RVC. Evaluation of immediate hypersensitivity skin tests to aeroallergens, measurement of total IgE and Candida albicans specific IgE and levels of IL-5 in 44 women with RVC and 26 with sporadic vaginal candidiasis (SVC). Statistical analyses were performed by Mann–Whitney test and χ(2) test with Yates correction. History of atopy (68%) and positive skin test (42%) were higher (P < 0·05) in RVC than in patients with SVC. No significant difference was found in total IgE, C. albicans specific IgE and IL-5 levels. There was a strong association between atopy and RVC, but type-2 immune response to C. albicans antigen was absent or similar in the two groups of patients

The Finland–United States Investigation of Non–Insulin-Dependent Diabetes Mellitus Genetics (FUSION) Study. I. An Autosomal Genome Scan for Genes That Predispose to Type 2 Diabetes

We performed a genome scan at an average resolution of 8 cM in 719 Finnish sib pairs with type 2 diabetes. Our strongest results are for chromosome 20, where we observe a weighted maximum LOD score (MLS) of 2.15 at map position 69.5 cM from pter and secondary weighted LOD-score peaks of 2.04 at 56.5 cM and 1.99 at 17.5 cM. Our next largest MLS is for chromosome 11 (MLS = 1.75 at 84.0 cM), followed by chromosomes 2 (MLS = 0.87 at 5.5 cM), 10 (MLS = 0.77 at 75.0 cM), and 6 (MLS = 0.61 at 112.5 cM), all under an additive model. When we condition on chromosome 2 at 8.5 cM, the MLS for chromosome 20 increases to 5.50 at 69.0 cM (P=.0014). An ordered-subsets analysis based on families with high or low diabetes-related quantitative traits yielded results that support the possible existence of disease-predisposing genes on chromosomes 6 and 10. Genomewide linkage-disequilibrium analysis using microsatellite marker data revealed strong evidence of association for D22S423 (P=.00007). Further analyses are being carried out to confirm and to refine the location of these putative diabetes-predisposing genes