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

KDEL receptors assist dengue virus exit from the endoplasmic reticulum

Membrane receptors at the surface of target cells are key host factors for virion entry; however, it is unknown whether trafficking and secretion of progeny virus requires host intracellular receptors. In this study, we demonstrate that dengue virus (DENV) interacts with KDEL receptors (KDELR), which cycle between the ER and Golgi apparatus, for vesicular transport from ER to Golgi. Depletion of KDELR by siRNA reduced egress of both DENV progeny and recombinant subviral particles (RSPs). Coimmunoprecipitation of KDELR with dengue structural protein prM required three positively charged residues at the N terminus, whose mutation disrupted protein interaction and inhibited RSP transport from the ER to the Golgi. Finally, siRNA depletion of class II Arfs, which results in KDELR accumulation in the Golgi, phenocopied results obtained with mutagenized prME and KDELR knockdown. Our results have uncovered a function for KDELR as an internal receptor involved in DENV trafficking.published_or_final_versio

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

Дослідження сорбційних властивостей фільтруючих матеріалів на основі композицій фосфат титану – пористий титан

Inorganic sorbents are more selective in comparison with commercial ion exchange resins towards of metal ions. However, inorganic sorbents characterized not high kinetic properties. One of the way to increase the kinetic rate of inorganic sorbents is to reduce the particle size of these materials, other way is synthesizing inorganic sorbents as porous products from powder materials. A sample of such inorganic sorbents is titanium phosphate of various compositions. Studying the properties of microfilters based on composition titanium phosphate - porous titanium has been developed. The sorbents based on acidic titanium phosphate Ti(HPO4)2-H2O were used for filtering solution with Fe(II) content. It is found that the number of impregnations with inorganic sorbent modificator is important and influence filtration process. The obtained results demonstrated that after the first impregnation of porous material with a smaller pore size, it is possible to obtain such sorbent as a mass content of powder material. By varying the ionic form of titanium phosphate, the porosity of titanium, the amount of impregnation, it could be possible effect on the sorption Fe(II). The sorption properties of titanium-titanium phosphate microfilters were studied by potentiometric titration in the NaCl-NaOH system, as well as the sorption of Fe2+ ions. The degree of purification for Fe(II) from solution with a concentration of 10 mg/l is 64 %. Application an electric potential to the microfilter of porous titanium - phosphate titanium increases the degree of purification of Fe(II) to 88 %.По відношенню до іонів металів неорганічні сорбенти є селективнішими порівняно з промисловими іонообмінними смолами, але ці сорбенти характеризуються невисокими кінетичними властивостями. Одним із способів підвищення кінетичної швидкості неорганічних сорбентів є зменшення розміру частинок цих матеріалів, іншим способом є синтез неорганічних сорбентів у вигляді пористих продуктів на основі порошкових матеріалів. Зразком таких неорганічних сорбентів є фосфат титану різного складу. Розроблено спосіб модифікації мікрофільтрів на основі композицій фосфат титану – пористий титан. В досліджені було використано сорбент на основі кислого фосфату титану (ФТ) складу Тi(НРО4)2-Н2О. Знайдено, що важливим є кількість просочень (імпрегнувань) модифікатором поверхні пористого мікрофільтра. Варіюючи іонну форму фосфат титану, пористість титану, кількість просочень (імпрегнувань), можна впливати на ступінь сорбції Fe(II) з розчинів під час фільтрації. Сорбційні властивості титантитанфосфатних мікрофільтрів досліджували шляхом потенціометричного титрування в системі NaCl-NaOH, а також сорбції іонів Fe(II). Ступінь очищення від Fe(II) розчинів, концентрація яких складала 10 мг/дм3 , становить 64 %. При накладанні електричного потенціалу до мікрофильтру пористий титан - фосфат титана, можна підвищити ступінь очищення Fe(II) до 88 %

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