Low cytosine triphosphate synthase 2 expression renders resistance to 5-fluorouracil in colorectal cancer

Understanding the determinants of resistance of 5-fluorouracil (5FU) is of significant value to optimizing administration of the drug, and introducing novel agents and treatment strategies. Here, the expression of 92 genes involved in 5FU transport, metabolism, co-factor (folate) metabolism and downstream effects was measured by real-time PCR low density arrays in 14 patient-derived colorectal cancer xenografts characterized for 5FU resistance. Candidate gene function was tested by siRNA and uridine modulation, and immunoblotting, apoptosis and cell cycle analysis. Predictive significance was tested by immunohistochemistry of tumors from 125 stage III colorectal cancer patients treated with and without 5FU. Of 8 genes significantly differentially expressed between 5FU sensitive and resistant xenograft tumors, CTPS2 was the gene with the highest probability of differential expression (p = 0.008). Reduction of CTPS2 expression by siRNA increased the resistance of colorectal cancer cell lines DLD1 and LS174T to 5FU and its analog, FUDR. CTPS2 siRNA significantly reduced cell S-phase accumulation and apoptosis following 5FU treatment. Exposure of cells to uridine, a precursor to the CTPS2 substrate uridine triphosphate, also increased 5FU resistance. Patients with low CTPS2 did not gain a survival benefit from 5FU treatment (p = 0.072), while those with high expression did (p = 0.003). Low CTPS2 expression may be a rationally-based determinant of 5FU resistance.

Structure-Based Mutational Analysis of eIF4E in Relation to sbm1 Resistance to Pea Seed-Borne Mosaic Virus in Pea

Background: Pea encodes eukaryotic translation initiation factor eIF4E (eIF4E(S)), which supports the multiplication of Pea seed-borne mosaic virus (PSbMV). In common with hosts for other potyviruses, some pea lines contain a recessive allele (sbm1) encoding a mutant eIF4E (eIF4E(R)) that fails to interact functionally with the PSbMV avirulence protein, VPg, giving genetic resistance to infection.

Molecular characterization and phylogenetic analysis of quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC and parE gene loci in viridans group streptococci isolated from adult patients with cystic fibrosis

This study demonstrated key resistance genes to fluroquinilones in Streptococcci isolated from sputum of people with CF. This suggests that other bacteria which are sometimes considered commensal may be a resovoir for resistance. Jse designed the study with Moore.

Abrasive wear resistance of electroless Ni-P coated aluminium after post treatment

Electroless nickel (EN) coatings are recognised for their hardness and wear resistance in automotive and aerospace industries. In this work, electroless Ni–P coatings were deposited on aluminium alloy substrate LM24 (Al–9 wt.% Si alloy) and the effect of post treatment on the wear resistance was studied. The post treatments included heat treatment and lapping with two different surface textures. Scanning electron microscopy (SEM), energy dispersive spectrometry (EDS), X-ray diffraction (XRD) and micro-abrasion tester were used to analyse morphology, structure and abrasive wear resistance of the coatings. Post heat treatment significantly improved the coating density and structure, giving rise to enhanced hardness and wear resistance. Microhardness of electroless Ni–P coatings with thickness of about 15 μm increased due to the formation of Ni3P after heat treatment.

Resistance, transition and exclusion: Politically motivated ex-prisoners and conflict transformation in Northern Ireland

The landscape of political imprisonment in Northern Ireland was changed due to the general release and reintegration of politically motivated prisoners as part of the Belfast Agreement. This article reflects upon the post-prison experiences of former prisoners and their families, and in particular how the move from a resistant to a transitional framework has facilitated a greater openness and willingness amongs ex-prisoners to acknowledge the personal and familial problems related to incarceration. We also explore the ways in which ex-prisoners have attempted to deal with the continued social, political and civic exclusion which arises as a result of their conflict-related 'criminal' convictions. In the final section of the article, the authors further develop the move from a resistant to a transitional characterization of incarceration and its consequences.