Psoriasis vulgaris is a complex chronic skin disease with immunological and genetic background. The most important predisposing genetic factors in psoriasis are genes of the human leukocyte antigen (HLA) region. Accumulative evidence has shown that several HLA alleles are closely associated with psoriasis; however, they tend to vary in different racial and ethnic backgrounds. One hundred forty-seven unrelated Slovak patients with psoriasis vulgaris (average age at onset 28?±?14 years) were genotyped for the HLA-C, DQB1 and DRB1 alleles by the polymerase chain reaction using sequence-specific primers. Allele frequencies observed in the group of psoriatic patients were compared to those obtained in the ethnically matched control group comprising 194 subjects with no history of psoriasis. Susceptibility to psoriasis vulgaris in our study group is significantly associated with HLA-C*06 (odds ratio (OR)?=?3.85), DRB1*07 (OR?=?2.56) and DQB1*02 (OR?=?1.09), respectively, whereas DRB*01 (OR?=?0.05) is associated negatively. Hereby, we provide the first report on the association of HLA-C, DRB1 and DQB1 alleles with psoriasis in the Slovak population. Our findings confirm HLA-C*06 and DRB1*07 as the most important genetic risk factors for psoriasis. However, the role of HLA genes as causative in the pathogenesis of the disease remains unclear. Identification of genetic factors that increase the risk of psoriasis is a precondition that helps to elucidate the pathogenesis of this troubling disease and identify targets for a more specific and effective therapy. 相似文献
Melanin has an important role in the ability of fungi to survive extreme conditions, like the high NaCl concentrations that are typical of hypersaline environments. The black fungus Hortaea werneckii that has been isolated from such environments has 1,8-dihydroxynaphthalene-melanin incorporated into the cell wall, which minimises the loss of glycerol at low NaCl concentrations. To further explore the role of melanin in the extremely halotolerant character of H. werneckii, we studied the effects of several melanin biosynthesis inhibitors on its growth, pigmentation and cell morphology. The most potent inhibitors were a 2,3-dihydrobenzofuran derivative and tricyclazole, which restricted the growth of H. werneckii on high-salinity media, as shown by growth curves and plate-drop assays. These inhibitors promoted release of the pigments from the H. werneckii cell surface and changed the medium colour. Inhibitor-treated H. werneckii cells exposed to high salinity showed both decreased and increased cell lengths. We speculate that this absence of melanin perturbs the integrity of the cell wall in H. werneckii, which affects its cell division and exposes it to the harmful effects of high NaCl concentrations. Surprisingly, melanin had no effect on H. werneckii survival under H2O2 oxidative stress. 相似文献
Photoinduced charge generation (PCG) dynamics are notoriously difficult to correlate with specific molecular properties in device relevant polymer:fullerene organic photovoltaic blend films due to the highly complex nature of the solid state blend morphology. Here, this study uses six judiciously selected trifluoromethylfullerenes blended with the prototypical polymer poly(3‐hexylthiophene) and measure the PCG dynamics in 50 fs–500 ns time scales with time‐resolved microwave conductivity and femtosecond transient absorption spectroscopy. The isomeric purity and thorough chemical characterization of the fullerenes used in this study allow for a detailed correlation between molecular properties, driving force, local intermolecular electronic coupling and, ultimately, the efficiency of PCG yield. The findings show that the molecular design of the fullerene not only determines inter‐fullerene electronic coupling, but also influences the decay dynamics of free holes in the donor phase even when the polymer microstructure remains unchanged. 相似文献
Protonation in the two-electron/two-proton reduction processes of 2,6-dichlorophenolindophenolate (DCIP) is investigated combining density functional theory (DFT) and molecular dynamics (MD) methods. DCIP (anion), DCIP?– (radical anion), and DCIP2? (dianion) are considered, including the electronic structure analysis from the prospective of quantum theory of atoms and molecules (QTAIM). It is shown that oxygen on the indophenolate moiety and nitrogen are the first and/or the second proton acceptor sites and their energetic order depends on the total charge of the system. MD simulations of differently charged species interacting with the solvent molecules have been performed for methanol, water, and oxonium cation (H3O+). Methanol and water molecules are found to form only hydrogen bonds with the solute irrespective of its charge. The calculated pKa values show that the imino group of DCIPH? is a weaker acid than water. While in the case of DCIP (and DCIP?–) plus oxonium cation, proton transfer from the solvent to the solute was evidenced for both aforementioned acceptor sites. In addition, MD simulations of bulks containing 15 and 43 molecules of water around the DCIP molecule have been performed, revealing the formation of 2–4 hydrogen bonds.
Graphical Abstract 2,6-Dichlorophenolindophenolate interacts with solvent molecules (water, oxonium cation and methanol). Hydrogen transfer and electronic structure are studied by DFT and molecular dynamics methods
European honey bees are highly important in crop pollination, increasing the value of global agricultural production by billions of dollars. Current knowledge about virulence and pathogenicity of Deformed wing virus (DWV), a major factor in honey bee colony mortality, is limited. With this study, we close the gap between field research and laboratory investigations by establishing a complete in vitro model for DWV pathogenesis. Infectious DWV was rescued from a molecular clone of a DWV-A genome that induces DWV symptoms such as crippled wings and discoloration. The expression of DWV proteins, production of infectious virus progeny, and DWV host cell tropism could be confirmed using newly generated anti-DWV monoclonal antibodies. The recombinant RNA fulfills Koch’s postulates circumventing the need of virus isolation and propagation of pure virus cultures. In conclusion, we describe the development and application of a reverse genetics system for the study of DWV pathogenesis. 相似文献
Scientific studies of society increasingly rely on digital traces produced by various aspects of human activity. In this paper, we exploit a relatively unexplored source of data–anonymized records of bank card transactions collected in Spain by a big European bank, and propose a new classification scheme of cities based on the economic behavior of their residents. First, we study how individual spending behavior is qualitatively and quantitatively affected by various factors such as customer’s age, gender, and size of his/her home city. We show that, similar to other socioeconomic urban quantities, individual spending activity exhibits a statistically significant superlinear scaling with city size. With respect to the general trends, we quantify the distinctive signature of each city in terms of residents’ spending behavior, independently from the effects of scale and demographic heterogeneity. Based on the comparison of city signatures, we build a novel classification of cities across Spain in three categories. That classification exhibits a substantial stability over different city definitions and connects with a meaningful socioeconomic interpretation. Furthermore, it corresponds with the ability of cities to attract foreign visitors, which is a particularly remarkable finding given that the classification was based exclusively on the behavioral patterns of city residents. This highlights the far-reaching applicability of the presented classification approach and its ability to discover patterns that go beyond the quantities directly involved in it. 相似文献
AbstractCarbonic anhydrase inhibitors (CAIs) are of growing interest since various isoforms of the enzyme are identified as promising drug targets for treatment of disease. The principal drawback of the clinically used CAIs is the lack of isoform selectivity, which may lead to observable side effects. Studies aiming at the design of isoform-selective CAIs entail generation and biological testing of arrays of compounds, which is a resource- and time-consuming process. Employment of multicomponent reactions is an efficient synthetic strategy in terms of gaining convenient and speedy access to a range of scaffolds with a high degree of molecular diversity. However, this powerful tool appears to be underutilized for the discovery of novel CAIs. A number of studies employing multicomponent reactions in CAI synthesis have been reported in literature. Some of these reports provide inspiring examples of successful use of multicomponent chemistry to construct novel potent and often isoform-selective inhibitors. On critical reading of several publications, however, it becomes apparent that for some chemical series designed as CAIs, the desired inhibitory properties are only assumed and never tested for. In these cases, the biological profile is reported based on the results of phenotypical cellular assays, with no correlation with the intended on-target activity. Present review aims at critically assessing the current literature on the multicomponent chemistry in the CAI design. 相似文献