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1.
The proliferative inflammatory atrophy (PIA) is considered as a possible precursor of prostate intraepithelial neoplasia (PIN)
or prostate cancer (PCa). In this study we assessed quantitatively the expression of AMACR, p63, COX-2, GST and iNOS in serial
paraffin-embedded tissue sections obtained after radical prostatectomy of PCa patients (n = 30). The applicability of these markers to distinguish PIA, PIN and PCa was evaluated. We also compared the immunohistochemical
expression profiles of AMACR, COX-2 and GST in the luminal and basal cells in lesions of PIN arisen in PIA or PIA alone. Two
different patterns of COX-2 expression according to the p63 status of the basal cells were found. This observation gives us
grounds to hypothesize that the diverse COX-2 patterns resulted from an initial basal cell damage which subsequently propagated
to its luminal secretory cells progeny. 相似文献
2.
Zega A Mlinsek G Solmajer T Trampus-Bakija A Stegnar M Urleb U 《Bioorganic & medicinal chemistry letters》2004,14(6):1563-1567
A series of azaphenylalanine derivatives were investigated as novel thrombin inhibitors based on the prodrug principle. By systematic structural modifications we have identified optimal groups for this series that led us to potent inhibitors of thrombin incorporating the benzamidine fragment at the P1 position, and their potentially orally active benzamidoxime prodrugs. The binding modes in the thrombin active site of two representative compounds were identified by X-ray crystallographic analysis. 相似文献
3.
Jeffrey J. Wine Damjan Glavač Gregory Hurlock Clare Robinson Margaret Lee Uros Potočnik Metka Ravnik-Glavač Michael Dean 《Mammalian genome》1998,9(4):301-305
Cystic fibrosis is a common human genetic disease caused by mutations in CFTR, a gene that codes for a chloride channel that
is regulated by phosphorylation and cytosolic nucleotides. As part of a program to discover natural animal models for human
genetic diseases, we have determined the genomic sequence of CFTR in the Rhesus monkey, Macaca mulatta. The coding region of rhesus CFTR is 98.3% identical to human CFTR at the nucleotide level and 98.2% identical and 99.7% similar at the amino acid level. Partial
sequences of flanking introns (5582 base pair positions analyzed) revealed 91.1% identity with human introns. Relative to
rhesus intronic sequence, the human sequences had 27 insertions and 22 deletions. Primer sequences for amplification of rhesus
genomic CFTR sequences are provided. The accession number is AF013753 (all 27 exons and some flanking intronic sequence).
Received: 27 August 1992 / Accepted: 5 December 1997 相似文献
4.
PHA-1 encodes a cytoplasmic protein that is required for embryonic morphogenesis and attachment of the foregut (pharynx) to the mouth (buccal capsule). Previous reports have in some cases suggested that PHA-1 is essential for the differentiation of most or all pharyngeal cell types. By performing mosaic analysis with a recently acquired pha-1 null mutation (tm3671), we found that PHA-1 is not required within most or all pharyngeal cells for their proper specification, differentiation, or function. Rather, our evidence suggests that PHA-1 acts in the arcade or anterior epithelial cells of the pharynx to promote attachment of the pharynx to the future buccal capsule. In addition, PHA-1 appears to be required in the epidermis for embryonic morphogenesis, in the excretory system for osmoregulation, and in the somatic gonad for normal ovulation and fertility. PHA-1 activity is also required within at least a subset of intestinal cells for viability. To better understand the role of PHA-1 in the epidermis, we analyzed several apical junction markers in pha-1(tm3671) homozygous embryos. PHA-1 regulates the expression of several components of two apical junction complexes including AJM-1–DLG-1/discs large complex and the classical cadherin–catenin complex, which may account for the role of PHA-1 in embryonic morphogenesis. 相似文献
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Kotnik M Humljan J Contreras-Martel C Oblak M Kristan K Hervé M Blanot D Urleb U Gobec S Dessen A Solmajer T 《Journal of molecular biology》2007,370(1):107-115
Mur ligases play an essential role in the intracellular biosynthesis of bacterial peptidoglycan, the main component of the bacterial cell wall, and represent attractive targets for the design of novel antibacterials. UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase (MurD) catalyses the addition of D-glutamic acid to the cytoplasmic intermediate UDP-N-acetylmuramoyl-L-alanine (UMA) and is the second in the series of Mur ligases. MurD ligase is highly stereospecific for its substrate, D-glutamic acid (D-Glu). Here, we report the high resolution crystal structures of MurD in complexes with two novel inhibitors designed to mimic the transition state of the reaction, which contain either the D-Glu or the L-Glu moiety. The binding modes of N-sulfonyl-D-Glu and N-sulfonyl-L-Glu derivatives were also characterised kinetically. The results of this study represent an excellent starting point for further development of novel inhibitors of this enzyme. 相似文献
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Karsenti E Acinas SG Bork P Bowler C De Vargas C Raes J Sullivan M Arendt D Benzoni F Claverie JM Follows M Gorsky G Hingamp P Iudicone D Jaillon O Kandels-Lewis S Krzic U Not F Ogata H Pesant S Reynaud EG Sardet C Sieracki ME Speich S Velayoudon D Weissenbach J Wincker P;Tara Oceans Consortium 《PLoS biology》2011,9(10):e1001177
The structure, robustness, and dynamics of ocean plankton ecosystems remain poorly understood due to sampling, analysis, and computational limitations. The Tara Oceans consortium organizes expeditions to help fill this gap at the global level. 相似文献
9.
SUMMARY: VizRank is a tool that finds interesting two-dimensional projections of class-labeled data. When applied to multi-dimensional functional genomics datasets, VizRank can systematically find relevant biological patterns. AVAILABILITY: http://www.ailab.si/supp/bi-vizrank SUPPLEMENTARY INFORMATION: http://www.ailab.si/supp/bi-vizrank. 相似文献
10.
Christensen KE Patel H Kuzmanov U Mejia NR MacKenzie RE 《The Journal of biological chemistry》2005,280(9):7597-7602
The Mthfd1 gene encoding the cytoplasmic methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase enzyme (DCS) was inactivated in embryonic stem cells. The null embryonic stem cells were used to generate spontaneously immortalized fibroblast cell lines that exhibit the expected purine auxotrophy. Elimination of these cytoplasmic activities allowed for the accurate assessment of similar activities encoded by other genes in these cells. A low level of 10-formyltetrahydrofolate synthetase was detected and was shown to be localized to mitochondria. However, NADP-dependent methylenetetrahydrofolate dehydrogenase activity was not detected. Northern blot analysis suggests that a recently identified mitochondrial DCS (Prasannan, P., Pike, S., Peng, K., Shane, B., and Appling, D. R. (2003) J. Biol. Chem. 278, 43178-43187) is responsible for the synthetase activity. The lack of NADP-dependent dehydrogenase activity suggests that this RNA may encode a monofunctional synthetase. Moreover, examination of the primary structure of this novel protein revealed mutations in key residues required for dehydrogenase and cyclohydrolase activities. This monofunctional synthetase completes the pathway for the production of formate from formyltetrahydrofolate in the mitochondria in our model of mammalian one-carbon folate metabolism in embryonic and transformed cells. 相似文献