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131.
Background
Methylation levels of genomic repeats such as long interspersed nucleotide elements (LINE-1) are representative of global methylation status and play an important role in maintenance of genomic stability. The objective of the study was to assess LINE-1 methylation status in colorectal cancer (CRC) in relation to adenomatous and malignant progression, tissue heterogeneity, and TNM-stage.Methodology/Principal Findings
DNA was collected by laser-capture microdissection (LCM) from normal, adenoma, and cancer tissue from 25 patients with TisN0M0 and from 92 primary CRC patients of various TNM-stages. The paraffin-embedded tissue sections were treated by in-situ DNA sodium bisulfite modification (SBM). LINE-1 hypomethylation index (LHI) was measured by absolute quantitative analysis of methylated alleles (AQAMA) realtime PCR; a greater index indicated enhanced hypomethylation. LHI in normal, cancer mesenchymal, adenoma, and CRC tissue was 0.38 (SD 0.07), 0.37 (SD 0.09), 0.49 (SD 0.10) and 0.53 (SD 0.08), respectively. LHI was significantly greater in adenoma tissue compared to its contiguous normal epithelium (P = 0.0003) and cancer mesenchymal tissue (P<0.0001). LHI did not differ significantly between adenoma and early cancer tissue of Tis stage (P = 0.20). LHI elevated with higher T-stage (P<0.04), was significantly greater in node-positive than node-negative CRC patients (P = 0.03), and was significantly greater in stage IV than all other disease stages (P<0.05).Conclusion/Significance
By using in-situ SBM and LCM cell selection we demonstrated early onset of LINE-1 demethylation during adenomatous change of colorectal epithelial cells and demonstrated that LINE-1 demethylation progression is linear in relation to TNM-stage progression. 相似文献132.
Studies were conducted to identify oil-based formulating agents (paraffinic oil, palm oil and emulsifiable adjuvant oils (EAOs))
for Metarhizium anisopliae that were superior to water with simple surfactants using a germination test and a bioassay against Boophilus microplus. Germination of conidia in all formulations, except 10% coconut EAO, produced more than 68% germination at 24 h and nearly
100% at 48 h. Coconut oil (average survival time (AST)=4.6±0.28 days) and 10% liquid paraffin EAO (AST=4.4±0.15 days) enhanced
the pathogenicity of M. anisopliae to B. microplus relative to water (AST=8.4±0.42 days). M. anisopliae in 10% liquid paraffin EAO was the most effective formulation having a moderately high germination after 24 h and a low AST
as well as a high AST in the control. In the second experiment, germination of conidia in 2% liquid paraffin EAO and 2% Cropspray
was higher than in 2% Codacide oil at 24 h, however, all treatments reached 100% germination after 48 h. The ASTs of the EAO
based M. anisopliae formulations (Average AST=6.4±0.54 days) were similar but lower that the ASTs of the controls (Average AST=9.6±0.28 days). 相似文献
133.
Ammiraju JS Yu Y Luo M Kudrna D Kim H Goicoechea JL Katayose Y Matsumoto T Wu J Sasaki T Wing RA 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2005,111(8):1596-1607
The International Rice Genome Sequencing Project has recently announced the high-quality finished sequence that covers nearly
95% of the japonica rice genome representing 370 Mbp. Nevertheless, the current physical map of japonica rice contains 62 physical gaps corresponding to approximately 5% of the genome, that have not been identified/represented
in the comprehensive array of publicly available BAC, PAC and other genomic library resources. Without finishing these gaps,
it is impossible to identify the complete complement of genes encoded by rice genome and will also leave us ignorant of some
5% of the genome and its unknown functions. In this article, we report the construction and characterization of a tenfold
redundant, 40 kbp insert fosmid library generated by random mechanical shearing. We demonstrated its utility in refining the
physical map of rice by identifying and in silico mapping 22 gap-specific fosmid clones with particular emphasis on chromosomes
1, 2, 6, 7, 8, 9 and 10. Further sequencing of 12 of the gap-specific fosmid clones uncovered unique rice genome sequence
that was not previously reported in the finished IRGSP sequence and emphasizes the need to complete finishing of the rice
genome.
Fosmid library reported here is publicly available from our web site 相似文献
134.
Hyaluronic acid production in Bacillus subtilis 总被引:1,自引:0,他引:1
Widner B Behr R Von Dollen S Tang M Heu T Sloma A Sternberg D Deangelis PL Weigel PH Brown S 《Applied and environmental microbiology》2005,71(7):3747-3752
The hasA gene from Streptococcus equisimilis, which encodes the enzyme hyaluronan synthase, has been expressed in Bacillus subtilis, resulting in the production of hyaluronic acid (HA) in the 1-MDa range. Artificial operons were assembled and tested, all of which contain the hasA gene along with one or more genes encoding enzymes involved in the synthesis of the UDP-precursor sugars that are required for HA synthesis. It was determined that the production of UDP-glucuronic acid is limiting in B. subtilis and that overexpressing the hasA gene along with the endogenous tuaD gene is sufficient for high-level production of HA. In addition, the B. subtilis-derived material was shown to be secreted and of high quality, comparable to commercially available sources of HA. 相似文献
135.
In summary, this project proposes to explore the feasibility of a new temporary implant and surgical technique to improve the DCR procedure. This is a significant improvement over current DCR practice for the following primary reasons: (1) it eliminates the risk of injury to both the eye and upper lacrimal system; (2) it permits tear flow into the nose immediately following surgery, potentially 6 months earlier than current practice and procedure, which frequently does not re-establish normal tear flow until stents are removed. Plans have been made to implant stents of different sizes and proportions into cadavers in order to test implantation and removal of the stent via external and intranasal approaches. 相似文献
136.
Leung S Holbrook A King B Lu HT Evans V Miyamoto N Mallari C Harvey S Davey D Ho E Li WW Parkinson J Horuk R Jaroch S Berger M Skuballa W West C Pulk R Phillips G Bryant J Subramanyam B Schaefer C Salamon H Lyons E Schilling D Seidel H Kraetzschmar J Snider M Perez D 《Journal of biomolecular screening》2005,10(2):157-167
Effector functions and proliferation of T helper (Th) cells are influenced by cytokines in the environment. Th1 cells respond to a synergistic effect of interleukin-12 (IL-12) and interleukin-18 (IL-18) to secrete interferon-gamma (IFN-gamma). In contrast, Th2 cells respond to interleukin-4 (IL-4) to secrete IL-4, interleukin-13 (IL-13), interleukin-5 (IL-5), and interleukin-10 (IL-10). The authors were interested in identifying nonpeptide inhibitors of the Th1 response selective for the IL-12/IL-18-mediated secretion of IFN-gamma while leaving the IL-4-mediated Th2 cytokine secretion relatively intact. The authors established a screening protocol using human peripheral blood mononuclear cells (PBMCs) and identified the hydrazino anthranilate compound 1 as a potent inhibitor of IL-12/IL-18-mediated IFN-gamma secretion from CD3(+) cells with an IC(50) around 200 nM. The inhibitor was specific because it had virtually no effect on IL-4-mediated IL-13 release from the same population of cells. Further work established that compound 1 was a potent intracellular iron chelator that inhibited both IL-12/IL-18- and IL-4-mediated T cell proliferation. Iron chelation affects multiple cellular pathways in T cells. Thus, the IL-12/IL-18-mediated proliferation and IFN-gamma secretion are very sensitive to intracellular iron concentration. However, the IL-4-mediated IL-13 secretion does not correlate with proliferation and is partially resistant to potent iron chelation. 相似文献
137.
Wyatt PG Allen MJ Borthwick AD Davies DE Exall AM Hatley RJ Irving WR Livermore DG Miller ND Nerozzi F Sollis SL Szardenings AK 《Bioorganic & medicinal chemistry letters》2005,15(10):2579-2582
This paper covers efforts to discover orally active potent and selective oxytocin antagonists. Screening pooled libraries identified a novel series of 2,5-diketopiperazine derivatives with antagonist activity at the human oxytocin receptor. We report the initial structure-activity relationship investigations and the determination of the stereochemistry of the most potent compounds. 相似文献
138.
Novel triazole based inhibitors of Ras farnesyl transferase 总被引:1,自引:0,他引:1
Saha AK Liu L Simoneaux R DeCorte B Meyer C Skrzat S Breslin HJ Kukla MJ End DW 《Bioorganic & medicinal chemistry letters》2005,15(24):5407-5411
A novel series of potent inhibitors of Ras farnesyl transferase possessing a 1,2,4-triazole pharmacophore is described. These inhibitors were discovered from a parallel synthesis effort and were subsequently optimized to in vitro IC50 value of less than 1 nM. 相似文献
139.
Shutler D Reece SE Mullie A Billingsley PF Read AF 《Proceedings. Biological sciences / The Royal Society》2005,272(1579):2397-2402
Several vector-borne infectious agents facultatively alter their life history strategies in response to local vector densities. Some evidence suggests that malaria parasites invest more heavily in transmission stage production (gametocytogenesis) when vectors are present. Such a strategy could rapidly increase malaria transmission rates, particularly when adult mosquitoes begin to appear after dry seasons. However, in contrast to a recent experiment with a rodent malaria (Plasmodium chabaudi), we found no change in gametocytogenesis in either P. chabaudi or in another rodent malaria, P. vinckei, when their mouse hosts were exposed to mosquitoes. Positive results in the earlier study may have been because mosquito-feeding caused anaemia in hosts, a known promoter of gametocytogenesis. The substantial evidence that malaria and a variety of other parasites facultatively alter transmission strategies in response to a variety of environmental influences makes our results surprising. 相似文献
140.
Wenming Wang Milos Tanurdzic Meizhong Luo Nicholas Sisneros Hye Ran Kim Jing-Ke Weng Dave Kudrna Christopher Mueller K Arumuganathan John Carlson Clint Chapple Claude de Pamphilis Dina Mandoli Jeff Tomkins Rod A Wing Jo Ann Banks 《BMC plant biology》2005,5(1):1-8