Innate transcriptional networks activated in bladder in response to uropathogenic Escherichia coli drive diverse biological pathways and rapid synthesis of IL-10 for defense against bacterial urinary tract infection

Early transcriptional activation events that occur in bladder immediately following bacterial urinary tract infection (UTI) are not well defined. In this study, we describe the whole bladder transcriptome of uropathogenic Escherichia coli (UPEC) cystitis in mice using genome-wide expression profiling to define the transcriptome of innate immune activation stemming from UPEC colonization of the bladder. Bladder RNA from female C57BL/6 mice, analyzed using 1.0 ST-Affymetrix microarrays, revealed extensive activation of diverse sets of innate immune response genes, including those that encode multiple IL-family members, receptors, metabolic regulators, MAPK activators, and lymphocyte signaling molecules. These were among 1564 genes differentially regulated at 2 h postinfection, highlighting a rapid and broad innate immune response to bladder colonization. Integrative systems-level analyses using InnateDB (http://www.innatedb.com) bioinformatics and ingenuity pathway analysis identified multiple distinct biological pathways in the bladder transcriptome with extensive involvement of lymphocyte signaling, cell cycle alterations, cytoskeletal, and metabolic changes. A key regulator of IL activity identified in the transcriptome was IL-10, which was analyzed functionally to reveal marked exacerbation of cystitis in IL-10–deficient mice. Studies of clinical UTI revealed significantly elevated urinary IL-10 in patients with UPEC cystitis, indicating a role for IL-10 in the innate response to human UTI. The whole bladder transcriptome presented in this work provides new insight into the diversity of innate factors that determine UTI on a genome-wide scale and will be valuable for further data mining. Identification of protective roles for other elements in the transcriptome will provide critical new insight into the complex cascade of events that underpin UTI.

Occupational and non-occupational risk factors in bladder cancer patients in an industrialized area located in former East-Germany [Berufliche und außerberufliche Risikofaktoren für das Harnblasenkarzinom in einem ehemaligen Industriegebiet der neuen Bundesländer]

Purpose: Several occupational carcinogens are metabolized by polymorphic enzymes. The distribution of the polymorphic enzymes N-acetyltransferase 2 (NAT2; substrates: aromatic amines), glutathione S-transferase M1 (GSTM1; substrates: e.g., reactive metabolites of polycyclic aromatic hydrocarbons), and glutathione S-transferase T1 (GSTT1; substrates: small molecules with 1-2 carbon atoms) were investigated. Material and Methods: At the urological department in Lutherstadt Wittenberg, 136 patients with a histologically proven transitional cell cancer of the urinary bladder were investigated for all occupations performed for more than 6 months. Several occupational and non-occupational risk factors were asked. The genotypes of NAT2, GSTM1, and GSTT1 were determined from leucocyte DNA by PCR. Results: Compared to the general population in Middle Europe, the percentage of GSTT1 negative persons (22.1 %) was ordinary; the percentage of slow acetylators (59.6%) was in the upper normal range, while the percentage of GSTM1 negative persons (58.8%) was elevated in the entire group. Shifts in the distribution of the genotypes were observed in subgroups who had been exposed to asbestos (6/6 GSTM1 negative, 5/6 slow acetylators), rubber manufacturing (8/10 GSTM1 negative), and chlorinated solvents (9/15 GSTM1 negative). Conclusions: The overrepresentation of GSTM1 negative bladder cancer patients also in this industrialized area and more pronounced in several occupationally exposed subgroups points to an impact of the GSTM1 negative genotype in bladder carcinogenesis. [Article in German]

Cyclododecane as support material for clean and facile transfer of large-area few-layer graphene

The transfer of chemical vapor deposited graphene is a crucial process, which can affect the quality of the transferred films and compromise their application in devices. Finding a robust and intrinsically clean material capable of easing the transfer of graphene without interfering with its properties remains a challenge. We here propose the use of an organic compound, cyclododecane, as a transfer material. This material can be easily spin coated on graphene and assist the transfer, leaving no residues and requiring no further removal processes. The effectiveness of this transfer method for few-layer graphene on a large area was evaluated and confirmed by microscopy, Raman spectroscopy, x-ray photoemission spectroscopy, and four-point probe measurements. Schottky-barrier solar cells with few-layer graphene were fabricated on silicon wafers by using the cyclododecane transfer method and outperformed reference cells made by standard methods.

Physical mechanism of the compressive response of F-actin networks : significance of crosslinker unbinding events

A model of crosslinker unbinding is implemented in a highly coarsegrained granular model of F-actin cytoskeleton. We employ this specific granular model to study the mechanisms of the compressive responses of F-actin networks. It is found that the compressive response of F-actin cytoskeleton has dependency on the strain rate. The evolution of deformation energy in the network indicates that crosslinker unbinding events can induce the remodelling of F-actin cytoskeleton in response to external loadings. The internal stress in F-actin cytoskeleton can efficiently dissipate with the help of crosslinker unbinding, which could lead to the spontaneous relaxation of living cells.

Application of XRF and correspondence analysis to provenance studies of coastal and inland archaeological pottery from the Mngeni river area, South Africa

XRF spectrometry was applied to provenance studies of Iron Age pottery specimens that originated from the Mngeni river area in South Africa. Ten transition metals (Sc to Zn) mere determined in 107 potsherds, excavated from four different sites. The data were subjected to a computerized mathematical technique (correspondence analysis), which was used to group the samples according to the similarity of their elemental distributions. The groupings were interpreted in terms of social or cultural interaction between the sites. (C) 1997 by John Wiley & Sons, Ltd.

The use of correspondence analysis to compare major and trace elements for provenance studies of iron-age pottery from the Mngeni river area, South Africa

Provenance studies of iron-age pottery specimens originating from the Mngeni river area in South Africa was carried out by applying XRF spectrometry. A total of sixteen major and trace elements were analysed in a batch of 107 potsherds, excavated from four different archaeological sites in the aforementioned area. A multivariate statistical programme Correspondence Analysis was used in this study to obtain the relevant clustering patterns according to the similarity of the elemental distributions. Differences and similarities in the clusters obtained for the majors and trace elements are discussed.