Genome sequences of actinobacteriophages JorRay, Blocker23, Nibbles, and OlgasClover.

JorRay, Blocker23, Nibbles, and OlgasClover are actinobacteriophages belonging to clusters G1, B2, CT, and DJ, respectively. JorRay and Blocker23 were identified in host bacterium Mycobacterium smegmatis mc2155. Nibbles and OlgasClover were identified in host bacterium Gordonia rubripertincta NRRL B-16540.

LINE-1 hypomethylation during primary colon cancer progression.

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.

Anti-IL-17A therapy protects against bone erosion in experimental models of rheumatoid arthritis.

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine secreted by a subset of memory T cells and other innate immune cells. It is associated with rheumatoid arthritis (RA) due to IL-17A expression in RA synovial fluid. The severe bone erosive rat adjuvant-induced arthritis (rAIA) and mouse collagen-induced arthritis (mCIA) models were used to address the therapeutic efficacy of anti-IL-17A treatment with a focused investigation on bone protection. In the rAIA model, treatment with anti-IL-17A completely alleviated arthritis, lowered the level of receptor activator of NFκB ligand (RANKL), and inhibited structural damage to the bones. In the mCIA model, IL-17A neutralization coincident with arthritis development or in mice with established arthritis diminished joint swelling by inhibiting disease initiation and progression. Intriguingly, even the few joints that became outwardly severely inflamed in the presence of an anti-IL-17A antagonist had diminished joint histopathology scores compared to severely inflamed, control-treated mice. The bone-preserving property correlated with decreased RANKL message in severely inflamed paws of arthritic mice. These data identify IL-17A as a key factor in inflammation-mediated bone destruction and support anti-IL-17A therapy for the treatment of inflammatory bone diseases such as RA.

Expression of caspase-14 reduces tumorigenicity of skin cancer cells.

BACKGROUND: The green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) possesses anti-carcinogenic properties and was found to induce terminal differentiation in epidermal keratinocytes. Caspase-14, a member of the caspase family associated with epithelial cell differentiation, planned cell death, and barrier formation, is induced by EGCG in normal human epidermal keratinocytes but not in cancer cells. MATERIALS AND METHODS: A human epidermoid cancer cell line, A431, was co-transfected with a caspase-14-expressing pCMV vector and a GFP/neo-etpressingpCMVvector. Cell growth and tumorigenicity of the stable transfectant were determined in comparison to cells transfected with the control GFP/neo-expressing pCMV vector. RESULTS: Expression of exogenous caspase-14 led to growth inhibition and reduced the tumorigenicity of A431 cells. CONCLUSION: Pending future studies, caspase-14 could be used as a novel approach to skin cancer therapy via gene delivery systems.