Inverse Association between Methylation of Human Papillomavirus Type 16 DNA and Risk of Cervical Intraepithelial Neoplasia Grades 2 or 3

The clinical relevance of human papillomavirus type 16 (HPV16) DNA methylation has not been well documented, although its role in modulation of viral transcription is recognized.Study subjects were 211 women attending Planned Parenthood clinics in Western Washington for routine Papanicolaou screening who were HPV16 positive at the screening and/or subsequent colposcopy visit. Methylation of 11 CpG dinucleotides in the 3' end of the long control region of the HPV16 genome was examined by sequencing the cloned polymerase chain reaction products. The association between risk of CIN2/3 and degree of CpG methylation was estimated using a logistic regression model.CIN2/3 was histologically confirmed in 94 (44.5%) of 211 HPV16 positive women. The likelihood of being diagnosed as CIN2/3 increased significantly with decreasing numbers of methylated CpGs (meCpGs) in the 3' end of the long control region (P(for trend) = 0.003). After adjusting for HPV16 variants, number of HPV16-positive visits, current smoking status and lifetime number of male sex partners, the odds ratio for the association of CIN2/3 with ≥4 meCpGs was 0.31 (95% confidence interval, 0.12-0.79). The proportion of ≥4 meCpGs decreased appreciably as the severity of the cervical lesion increased (P(for trend) = 0.001). The inverse association remained similar when CIN3 was used as the clinical endpoint. Although not statistically significant, the ≥4 meCpGs-related risk reduction was more substantial among current, as compared to noncurrent, smokers.Results suggest that degree of the viral genome methylation is related to the outcome of an HPV16 cervical infection

Pretreatment and enzymatic hydrolysis of lignocellulosic biomass for reducing sugar production

Conversion of lignocellulosic biomass into reducing sugar has contributed to an alternative use of lignocellulose source, especially in the production of value-added products such as amino acids, biofuels, and vitamins. In the bioconversion process, pretreatment of lignocellulosic biomass is important to enhance the accessibility of enzyme hydrolysis, thus increasing the yield of reducing sugar. Lignocellulosic biomass has a very complex arrangement of structure that needs a proper study in pretreatment and enzymatic hydrolysis process to obtain an optimum yield of reducing sugar. This chapter discusses chemical and enzymatic pretreatment methods that are commonly applied to effectively modify the chemical structures of lignocellulosic biomass. Acid pretreatment using dilute sulfuric acid (H2SO4) is the most commonly employed for chemical pretreatment while sodium hydroxide (NaOH) is the most commonly applied for alkaline pretreatment because of its ability to delignify biomass. Then, enzymatic hydrolysis of lignocellulosic biomass for the production of reducing sugar is discussed in detail. The kinetics and optimization of hydrolysis which are the key parameters that determine the yields of reducing sugar are also presented. The right pretreatment method combined with an efficient hydrolysis process will ensure successful conversion of lignocellulosic biomass into reducing sugar, thus providing a sustainable production of reducing sugar from biomass for various applications

Sheep herd management during the Early Neolithic in the inland of the Iberian Peninsula. Isotopic analyses of El Mirador cave (Sierra de Atapuerca, Spain)

The beginning of husbandry in the Iberian Peninsula has been documented from the second half of the 6th millennium BCE and was based on the breeding of domestic caprines, mainly sheep. The first evidence of these practices comes from the Mediterranean region, but they quickly expanded inland. Previous studies have reported on the importance of the El Mirador sheepfold cave (Sierra de Atapuerca, Burgos, Spain) for understanding the process of the adoption of a farming economy in this inland region. In this study, we focus on husbandry and sheep management occurring in the 6th and 5th millennium cal BCE occupations of El Mirador cave by means of sequential oxygen (δ18O) and carbon (δ13C) isotope analyses in sheep molar tooth enamel. The results show a rapid adaptation and adoption of domestic sheep in the inland of the Iberian Peninsula. In El Mirador cave, well-organised sheep breeding was developed based on the concentration of births at the end of winter and early spring, for a period of ~2.64 months, which made husbandry more compatible with other economic activities. In 5th millennium levels, autumn births were also documented and may be indicative of the intervention of the shepherd in the reproductive cycle of the sheep and of a progressive adaptation of these animals to the interior of the Peninsula. All these strategies may have been supported by the recurrent occupations of the sheepfold, flocks grazing in the areas surrounding the cave and the possible use of leaf fodder in winter