Sources of Sex Information Used by Young British Women Who Have Sex with Women (WSW) and Women Who Have Sex Exclusively with Men (WSEM): Evidence from the National Survey of Sexual Attitudes and Lifestyles

There is little consideration about the provision of information about sex to women who have sex with women (WSW). This study drew on data from the third National Survey of Sexual Attitudes and Lifestyle, a nationally representative survey of people in Great Britain. Logistic regression was undertaken to examine firstly the relationships between WSW and women who have sex exclusively with men (WSEM) and their main source of information about sex, and secondly between WSW/WSEM and unmet need for information about sex. Each source was included as the binary outcome indicating yes this was the main source, or no this was not the main source of information about sex. The results found that WSW had significantly lower odds of reporting lessons at schools as their main source of information, and significantly higher odds of reporting sources defined as ‘other’ (predominantly first girlfriend/boyfriend or sexual partner) as their main source of information. Reported levels of unmet need for information was also higher amongst young WSW compared with WSEM. This study provides new insights into the sex educational needs of young women and highlights the need for sex education in schools in Great Britain to include information on a full-range of sexual practices, including same-sex sexual relationships

Surface induced disorder in body-centered cubic alloys

We present Monte Carlo simulations of surface induced disordering in a model of a binary alloy on a bcc lattice which undergoes a first order bulk transition from the ordered DO3 phase to the disordered A2 phase. The data are analyzed in terms of an effective interface Hamiltonian for a system with several order parameters in the framework of the linear renormalization approach due to Brezin, Halperin and Leibler. We show that the model provides a good description of the system in the vicinity of the interface. In particular, we recover the logarithmic divergence of the thickness of the disordered layer as the bulk transition is approached, we calculate the critical behavior of the maxima of the layer susceptibilities, and demonstrate that it is in reasonable agreement with the simulation data. Directly at the (110) surface, the theory predicts that all order parameters vanish continuously at the surface with a nonuniversal, but common critical exponent. However, we find different exponents for the order parameter of the DO3 phase and the order parameter of the B2 phase. Using the effective interface model, we derive the finite size scaling function for the surface order parameter and show that the theory accounts well for the finite size behavior of the DO3 ordering but not for that of B2 ordering. The situation is even more complicated in the neighborhood of the (100) surface, due to the presence of an ordering field which couples to the B2 order.Comment: To appear in Physical Review

A multicenter phase II study of the combination of oxaliplatin, irinotecan and capecitabine in the first-line treatment of metastatic colorectal cancer

The triple drug combination consisting of irinotecan, oxaliplatin and 5-fluorouracil (FOLFOXIRI) has demonstrated higher activity and efficacy compared to the doublet FOLFIRI. 5-Fluorouracil could be substituted in FOLFOXIRI regimen by capecitabine, an oral fluoropyrimidine with similar efficacy. Recently, a dose-finding trial has demonstrated the feasibility of the combination of irinotecan, oxaliplatin and capecitabine (XELOXIRI) and established their recommended doses. The aim of this study was to evaluate the activity of XELOXIRI. A total of 36 patients with unresectable metastatic colorectal cancer received irinotecan 165 mg m−2 and oxaliplatin 85 mg m−2 on day 1 plus capecitabine 2000 mg m−2 per day orally in two doses from day 1 to day 7, every 2 weeks. Grade 3–4 toxicities were infrequent, expect for neutropenia and diarrhoea, which were each observed in 30% of patients. Two complete and twenty-two partial responses were obtained, corresponding to an overall response rate of 67% (95% CI 51.4–82%). After a median follow-up of 17.7 months, the median progression-free and overall survival were 10.1 and 17.9 months, respectively

Extending Epigenesis: From Phenotypic Plasticity to the Bio-Cultural Feedback

The paper aims at proposing an extended notion of epigenesis acknowledging an actual causal import to the phenotypic dimension for the evolutionary diversification of life forms. Section 1 offers introductory remarks on the issue of epigenesis contrasting it with ancient and modern preformationist views. In Section 2 we propose to intend epigenesis as a process of phenotypic formation and diversification a) dependent on environmental influences, b) independent of changes in the genomic nucleotide sequence, and c) occurring during the whole life span. Then, Section 3 focuses on phenotypic plasticity and offers an overview of basic properties (like robustness, modularity and degeneracy) that allows biological systems to be evolvable – i.e. to have the potentiality of producing phenotypic variation. Successively (Section 4), the emphasis is put on environmentally-induced modification in the regulation of gene expression giving rise to phenotypic variation and diversification. After some brief considerations on the debated issue of epigenetic inheritance (Section 5), the issue of culture (kept in the background of the preceding sections) is considered. The key point is that, in the case of humans and of the evolutionary history of the genus Homo at least, the environment is also, importantly, the cultural environment. Thus, Section 6 argues that a bio-cultural feedback should be acknowledged in the “epigenic” processes leading to phenotypic diversification and innovation in Homo evolution. Finally, Section 7 introduces the notion of “cultural neural reuse”, which refers to phenotypic/neural modifications induced by specific features of the cultural environment that are effective in human cultural evolution without involving genetic changes. Therefore, cultural neural reuse may be regarded as a key instance of the bio-cultural feedback and ultimately of the extended notion of epigenesis proposed in this work

Sidestream cigarette smoke effects on cardiovascular responses in conscious rats: involvement of oxidative stress in the fourth cerebral ventricle

Background: Cigarette exposure increases brain oxidative stress. The literature showed that increased brain oxidative stress affects cardiovascular regulation. However, no previous study investigated the involvement of brain oxidative stress in animals exposed to cigarette and its relationship with cardiovascular regulation. We aimed to evaluate the effects of central catalase inhibition on baroreflex and cardiovascular responses in rats exposed to sidestream cigarette smoke (SSCS). Methods: We evaluated males Wistar rats (320-370 g), which were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4th V). Femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. Rats were exposed to SSCS during three weeks, 180 minutes, 5 days/week (CO: 100-300 ppm). Baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 mu g/kg, bolus) to induce bradycardic reflex and a depressor dose of sodium nitroprusside (SNP, 50 mu g/kg, bolus) to induce tachycardic reflex. Cardiovascular responses were evaluated before, 5, 15, 30 and 60 minutes after 3-amino-1,2,4-triazole (ATZ, catalase inhibitor, 0.001 g/100 mu L) injection into the 4th V. Results: Central catalase inhibition increased basal HR in the control group during the first 5 minutes. SSCS exposure increased basal HR and attenuated bradycardic peak during the first 15 minutes. Conclusion: We suggest that SSCS exposure affects cardiovascular regulation through its influence on catalase activity.Foundation of Support to Research of Sao Paulo State (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP [07/59127-9

Intracellular Serine Protease Inhibitor SERPINB4 Inhibits Granzyme M-Induced Cell Death

Granzyme-mediated cell death is the major pathway for cytotoxic lymphocytes to kill virus-infected and tumor cells. In humans, five different granzymes (i.e. GrA, GrB, GrH, GrK, and GrM) are known that all induce cell death. Expression of intracellular serine protease inhibitors (serpins) is one of the mechanisms by which tumor cells evade cytotoxic lymphocyte-mediated killing. Intracellular expression of SERPINB9 by tumor cells renders them resistant to GrB-induced apoptosis. In contrast to GrB, however, no physiological intracellular inhibitors are known for the other four human granzymes. In the present study, we show that SERPINB4 formed a typical serpin-protease SDS-stable complex with both recombinant and native human GrM. Mutation of the P2-P1-P1′ triplet in the SERPINB4 reactive center loop completely abolished complex formation with GrM and N-terminal sequencing revealed that GrM cleaves SERPINB4 after P1-Leu. SERPINB4 inhibited GrM activity with a stoichiometry of inhibition of 1.6 and an apparent second order rate constant of 1.3×104 M−1s−1. SERPINB4 abolished cleavage of the macromolecular GrM substrates α-tubulin and nucleophosmin. Overexpression of SERPINB4 in tumor cells inhibited recombinant GrM-induced as well as NK cell-mediated cell death and this inhibition depended on the reactive center loop of the serpin. As SERPINB4 is highly expressed by squamous cell carcinomas, our results may represent a novel mechanism by which these tumor cells evade cytotoxic lymphocyte-induced GrM-mediated cell death

Investigating Behaviour and Population Dynamics of Striped Marlin (Kajikia audax) from the Southwest Pacific Ocean with Satellite Tags

Behaviour and distribution of striped marlin within the southwest Pacific Ocean were investigated using electronic tagging data collected from 2005–2008. A continuous-time correlated random-walk Kalman filter was used to integrate double-tagging data exhibiting variable error structures into movement trajectories composed of regular time-steps. This state-space trajectory integration approach improved longitude and latitude error distributions by 38.5 km and 22.2 km respectively. Using these trajectories as inputs, a behavioural classification model was developed to infer when, and where, ‘transiting’ and ‘area-restricted’ (ARB) pseudo-behavioural states occurred. ARB tended to occur at shallower depths (108±49 m) than did transiting behaviours (127±57 m). A 16 day post-release period of diminished ARB activity suggests that patterns of behaviour were affected by the capture and/or tagging events, implying that tagged animals may exhibit atypical behaviour upon release. The striped marlin in this study dove deeper and spent greater time at ≥200 m depth than those in the central and eastern Pacific Ocean. As marlin reached tropical latitudes (20–21°S) they consistently reversed directions, increased swimming speed and shifted to transiting behaviour. Reversals in the tropics also coincided with increases in swimming depth, including increased time ≥250 m. Our research provides enhanced understanding of the behavioural ecology of striped marlin. This has implications for the effectiveness of spatially explicit population models and we demonstrate the need to consider geographic variation when standardizing CPUE by depth, and provide data to inform natural and recreational fishing mortality parameters

EPHA2 Is Associated with Age-Related Cortical Cataract in Mice and Humans

Age-related cataract is a major cause of blindness worldwide, and cortical cataract is the second most prevalent type of age-related cataract. Although a significant fraction of age-related cataract is heritable, the genetic basis remains to be elucidated. We report that homozygous deletion of Epha2 in two independent strains of mice developed progressive cortical cataract. Retroillumination revealed development of cortical vacuoles at one month of age; visible cataract appeared around three months, which progressed to mature cataract by six months. EPHA2 protein expression in the lens is spatially and temporally regulated. It is low in anterior epithelial cells, upregulated as the cells enter differentiation at the equator, strongly expressed in the cortical fiber cells, but absent in the nuclei. Deletion of Epha2 caused a significant increase in the expression of HSP25 (murine homologue of human HSP27) before the onset of cataract. The overexpressed HSP25 was in an underphosphorylated form, indicating excessive cellular stress and protein misfolding. The orthologous human EPHA2 gene on chromosome 1p36 was tested in three independent worldwide Caucasian populations for allelic association with cortical cataract. Common variants in EPHA2 were found that showed significant association with cortical cataract, and rs6678616 was the most significant in meta-analyses. In addition, we sequenced exons of EPHA2 in linked families and identified a new missense mutation, Arg721Gln, in the protein kinase domain that significantly alters EPHA2 functions in cellular and biochemical assays. Thus, converging evidence from humans and mice suggests that EPHA2 is important in maintaining lens clarity with age

Terrestrialization, Miniaturization and Rates of Diversification in African Puddle Frogs (Anura: Phrynobatrachidae)

Terrestrialization, the evolution of non-aquatic oviposition, and miniaturization, the evolution of tiny adult body size, are recurring trends in amphibian evolution, but the relationships among the traits that characterize these phenomena are not well understood. Furthermore, these traits have been identified as possible “key innovations” that are predicted to increase rates of speciation in those lineages in which they evolve. We examine terrestrialization and miniaturization in sub-Saharan puddle frogs (Phrynobatrachidae) in a phylogenetic context to investigate the relationship between adaptation and diversification through time. We use relative dating techniques to ascertain if character trait shifts are associated with increased diversification rates, and we evaluate the likelihood that a single temporal event can explain the evolution of those traits. Results indicate alternate reproductive modes evolved independently in Phrynobatrachus at least seven times, including terrestrial deposition of eggs and terrestrial, non-feeding larvae. These shifts towards alternate reproductive modes are not linked to a common temporal event. Contrary to the “key innovations” hypothesis, clades that exhibit alternate reproductive modes have lower diversification rates than those that deposit eggs aquatically. Adult habitat, pedal webbing and body size have no effect on diversification rates. Though these traits putatively identified as key innovations for Phrynobatrachus do not seem to be associated with increased speciation rates, they may still provide opportunities to extend into new niches, thus increasing overall diversity