Mutations in the human CSB gene cause Cockayne syndrome (CS). In addition to increased photosensitivity, CS patients suffer from severe developmental abnormalities, including growth retardation and mental retardation. Whereas a deficiency in the preferential repair of UV lesions from the transcribed strand accounts for the increased photosensitivity of CS patients, the reason for developmental defects in these individuals has remained unclear. Here we provide in vivo evidence for a role of RAD26, the counterpart of the CSB gene in Saccharomyces cerevisiae, in transcription elongation by RNA polymerase II, and in addition we show that under conditions requiring rapid synthesis of new mRNAs, growth is considerably reduced in cells lacking RAD26. These findings implicate a role for CSB in transcription elongation, and they strongly suggest that impaired transcription elongation is the underlying cause of the developmental problems in CS patients.Cockayne syndrome (CS) in humans is characterized by severe growth retardation that has the outward appearance of cachetic dwarfism, and CS patients suffer from progressive neurologic dysfunction and mental retardation. CS individuals also exhibit mild sun sensitivity, but they do not suffer from the increased incidence of skin cancers so prevalent in xeroderma pigmentosum patients. The mean age of death in CS patients is ϳ12 years (13). Mutations in two human genes, CSA and CSB, account for over 90% of CS cases (8). CS cells are impaired in their ability to perform preferential repair of DNA lesions from the transcribed strand (21), a phenomenon known as transcription-coupled repair (TCR) (11). Although the defect in preferential repair of UV lesions from the transcribed strand explains the photosensitivity of CS patients, it fails to account for the characteristic growth and neurological defects associated with CS.RAD26 is the CSB counterpart in Saccharomyces cerevisiae, and inactivation of this gene causes a defect in the TCR of UV-damaged DNA (20). The proteins encoded by the RAD26 and CSB genes are members of the SWI2/SNF2 family of ATPases, and both proteins have DNA-dependent ATPase activities (6, 17). Interestingly, in vitro studies with the purified human CSB protein have suggested a role for CSB as an RNA polymerase II (Pol II) elongation factor (16). Here we utilize S. cerevisiae as a model to investigate the role of RAD26 in transcription elongation in vivo and to examine the possibility that the clinical features of CS patients derive from defects in transcription elongation.Elongation factor SII enables Pol II to transcribe through intrinsic arrest sites in DNA. SII binds arrested Pol II and activates the cleavage of nascent transcript by a latent endoribonuclease intrinsic to Pol II, which eventually results in the clearance of the impediment (15). In S. cerevisiae, DST1, the gene encoding SII, is not essential for viability; however, the dst1⌬ mutant exhibits enhanced sensitivity to the base analog 6-azauracil (6AU) (12), which depletes cellular levels of th...

Microlenses and microlens arrays were fabricated using a novel fabrication technology based on the exposure of a resist (usually PMMA) to deep x-rays and subsequent thermal treatment. The fabrication technology is very simple and produces microlenses and microlens arrays with good surface roughness (less than 1 nm). The molecular weight and glass transition temperature of PMMA is reduced when it is irradiated with deep x-rays. The microlenses were produced through the effects of volume change, surface tension, and reflow during thermal treatment of irradiated PMMA. The geometry of the microlens was determined by parameters such as the x-ray dose applied to the PMMA, the diameter of the microlens, along with the heating temperature, heating time and cooling rate in the thermal treatment. Microlenses were produced with diameters ranging from 30 to 1500 μm. The modified LIGA process was used to construct not only hemispherical microlenses, but also structures that were rectangular-shaped, star-shaped, etc.

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The aim of the present study was to evaluate the effects on the susceptibility to colorectal cancer (CRC) of genetic polymorphisms in P-glycoprotein (PGP) and the metabolic enzymes cytochrome P450 1A2 (CYP1A2) and flavin-containing monooxygenase 3 (FMO3). We analyzed five single-nucleotide polymorphisms (SNP) in 93 cancer-free volunteers and 111 patients with CRC: one common genetic variant of the PGP-encoding MDR1 gene and four SNP in genes for metabolic enzymes (two SNP in FMO3 and two SNP in CYP1A2). The genotypes and allele frequencies of the MDR1/C3435T, FMO3/G488A, FMO3/A923G and CYP1A2/G-3860 A polymorphisms were not significantly different in cancerfree subjects and CRC patients. However, a significant association was found between the CYP1A2/A-163C polymorphism and the risk of CRC, particularly in elderly (>55 years) subjects and smokers. A phenotyping study in normal smokers showed that the CYP1A2 activity of subjects with the CYP1A2/− − − −163 AA genotype was significantly lower than that of subjects carrying the CYP1A2 (1-6) The carcinogens that cause the development of CRC enter the body as (pro)carcinogens via transporters, (7)(8)(9) and are activated to carcinogens or eliminated by various enzymes.(10) These toxicokinetic-related proteins are also controlled by our genetic background (e.g. by genetic polymorphisms). In considering the effects of genetic polymorphisms on the toxicokinetic profiles of xenobiotics, particularly (pro) carcinogens, we must evaluate the combined effects of genetic polymorphisms in both transporters and metabolic enzymes.To date, numerous studies have been conducted to correlate the genetic polymorphisms of single proteins and the risk of disease development or progression. In particular, genetic polymorphisms in drug metabolizing enzymes, such as the cytochrome P450 1 (CYP1A) family, (11,12) glutathione Stransferases, (13) N-acetyltransferases (14) and UDP-glucuronosyltransferases, (15) are the most well-known and important genetic factors in the development of CRC. Flavin-containing monooxygenase 3 (FMO3) is one of the major hepatic metabolic enzymes that catalyze the NADPH-dependent attachment of molecular oxygen to endogenous and foreign chemicals containing nucleophilic N, S and P heteroatoms. There are few studies of the relationship between FMO3 activity and carcinogenesis. A drug transporter, P-glycoprotein (PGP), is a recognized gatekeeper that limits the accumulation of xenobiotics in the body by facilitating ATPconsuming efflux. Recently, studies of the relationship between MDR1 polymorphisms and disease susceptibility have been conducted. (16,17) However, there has been no report of the relationship between the combined genetic polymorphisms of drug transporters and metabolic enzymes and CRC development.Against this background, we analyzed the common genetic polymorphisms in the genes for the drug transporter MDR1 and the metabolic enzymes CYP1A2 and FMO3, and attempted to elucidate the association between these polymorphisms and sporadic CRC in Koreans. We a...

We propose a method to capture light ray field of three-dimensional scene using focal plane sweeping. Multiple images are captured using a usual camera at different focal distances, spanning the three-dimensional scene. The captured images are then back-projected to four-dimensional spatio-angular space to obtain the light ray field. The obtained light ray field can be visualized either using digital processing or optical reconstruction using various three-dimensional display techniques including integral imaging, layered display, and holography.