Drag Force Minimizing Shape Identification of Body Located in Compressible Fluid Flow

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv

Dominant negative mutant Cyclin T1 proteins inhibit HIV transcription by specifically degrading Tat

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Nestin expression in the kidney with an obstructed ureter

Nestin is an intermediate filament protein originally identified in neuroepithelial stem cells. This cytoskeletal-associated protein is also expressed in some non-neuronal organs including renal tubular cells and glomerular endothelial cells during kidney development. Little is known, however, about nestin expression in the kidney during injury. In this study, we find nestin expression induced in renal tubular and interstitial myofibroblasts in the adult rat kidney following unilateral ureteral obstruction. The degree of nestin expression was well correlated with the degree of tubulointerstitial fibrosis. Immunohistochemical identification of specific nephron segments showed that nestin was primarily expressed by proximal tubules, partially by distal tubules and thick ascending limbs of Henle but not by collecting ducts. The nestin-positive tubular cells also expressed vimentin and heat-shock protein 47 (HSP47) suggesting these cells reverted to a mesenchymal phenotype. Not all vimentin- or HSP-expressing cells expressed nestin; however, suggesting that nestin is distinct from these conventional mesenchymal markers. Nestin expression was also found associated with phenotypical changes in cultured renal cells induced by hypoxia or transforming growth factor-β. Nestin expression was located in hypoxic regions of the kidney with an obstructed ureter. Our results indicate that nestin could be a novel marker for tubulointerstitial injury

Genetic enhancement of behavioral itch responses in mice lacking phosphoinositide 3-kinase-γ (PI3Kγ)

Phosphoinositide 3-kinases (PI3Ks) are important for synaptic plasticity and various brain functions. The only class IB isoform of PI3K, PI3Kγ, has received the most attention due to its unique roles in synaptic plasticity and cognition. However, the potential role of PI3Kγ in sensory transmission, such as pain and itch has not been examined. In this study, we present the evidence for the first time, that genetic deletion of PI3Kγ enhanced scratching behaviours in histamine-dependent and protease-activated receptor 2 (PAR-2)-dependent itch. In contrast, PI3Kγ-deficient mice did not exhibit enhanced scratching in chloroquine-induced itch, suggesting that PI3Kγ selectively contributes to certain types of behavioal itch response. Furthermore, PI3Kγ-deficient mice exhibited normal acute nociceptive responses to thermal and mechanical noxious stimuli. Behavioral licking responses to intraplantar injections of formalin and mechanical allodynia in a chronic inflammatory pain model (CFA) were also not affected by PI3Kγ gene deletion. Our findings indicate that PI3Kγ selectively contributes to behavioral itching induced by histamine and PAR-2 agonist, but not chloroquine agonist

Genopal™: A Novel Hollow Fibre Array for Focused Microarray Analysis

Expression profiling of target genes in patient blood is a powerful tool for RNA diagnosis. Here, we describe Genopal™, a novel platform ideal for efficient focused microarray analysis. Genopal™, which consists of gel-filled fibres, is advantageous for high-quality mass production via large-scale slicing of the Genopal™ block. We prepared two arrays, infectant and autoimmunity, that provided highly reliable data in terms of repetitive scanning of the same and/or distinct microarrays. Moreover, we demonstrated that Genopal™ had sensitivity sufficient to yield signals in short hybridization times (0.5 h). Application of the autoimmunity array to blood samples allowed us to identify an expression pattern specific to Takayasu arteritis based on the Spearman rank correlation by comparing the reference profile with those of several autoimmune diseases and healthy volunteers (HVs). The comparison of these data with those obtained by other methods revealed that they exhibited similar expression profiles of many target genes. Taken together, these data demonstrate that Genopal™ is an advantageous platform for focused microarrays with regard to its low cost, rapid results and reliable quality

Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polη in cellular response to various DNA lesions

Replicative DNA polymerases are frequently stalled by DNA lesions. The resulting replication blockage is released by homologous recombination (HR) and translesion DNA synthesis (TLS). TLS employs specialized TLS polymerases to bypass DNA lesions. We provide striking in vivo evidence of the cooperation between DNA polymerase η, which is mutated in the variant form of the cancer predisposition disorder xeroderma pigmentosum (XP-V), and DNA polymerase ζ by generating POLη−/−/POLζ−/− cells from the chicken DT40 cell line. POLζ−/− cells are hypersensitive to a very wide range of DNA damaging agents, whereas XP-V cells exhibit moderate sensitivity to ultraviolet light (UV) only in the presence of caffeine treatment and exhibit no significant sensitivity to any other damaging agents. It is therefore widely believed that Polη plays a very specific role in cellular tolerance to UV-induced DNA damage. The evidence we present challenges this assumption. The phenotypic analysis of POLη−/−/POLζ−/− cells shows that, unexpectedly, the loss of Polη significantly rescued all mutant phenotypes of POLζ−/− cells and results in the restoration of the DNA damage tolerance by a backup pathway including HR. Taken together, Polη contributes to a much wide range of TLS events than had been predicted by the phenotype of XP-V cells