Comprehensive Transcriptome Analysis of Sex-Biased Expressed Genes Reveals Discrete Biological and Physiological Features of Male and Female Schistosoma japonicum

Schistosomiasis is a chronic and debilitating disease caused by blood flukes (digenetic trematodes) of the genus Schistosoma. Schistosomes are sexually dimorphic and exhibit dramatic morphological changes during a complex lifecycle which requires subtle gene regulatory mechanisms to fulfil these complex biological processes. In the current study, a 41,982 features custom DNA microarray, which represents the most comprehensive probe coverage for any schistosome transcriptome study, was designed based on public domain and local databases to explore differential gene expression in S. japonicum. We found that approximately 1/10 of the total annotated genes in the S. japonicum genome are differentially expressed between adult males and females. In general, genes associated with the cytoskeleton, and motor and neuronal activities were readily expressed in male adult worms, whereas genes involved in amino acid metabolism, nucleotide biosynthesis, gluconeogenesis, glycosylation, cell cycle processes, DNA synthesis and genome fidelity and stability were enriched in females. Further, miRNAs target sites within these gene sets were predicted, which provides a scenario whereby the miRNAs potentially regulate these sex-biased expressed genes. The study significantly expands the expressional and regulatory characteristics of gender-biased expressed genes in schistosomes with high accuracy. The data provide a better appreciation of the biological and physiological features of male and female schistosome parasites, which may lead to novel vaccine targets and the development of new therapeutic interventions.

Biosensor-based detection of reduced sex hormone-binding globulin binding capacities in response to growth-promoter administrations

Growth-promoting agents are illicitly used during animal rearing processes and the detection of their use is limited by new compounds and dosing practices that limit the efficiency of current testing which is based on residue analysis by liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatography–mass spectrometry (GC–MS) methodology. An alternative approach is to use indirect biological evidence as a screening tool to identify growth-promoter treated animals thus improving the effectiveness of residue testing through the targeted sampling of these animals. Sex hormone-binding globulin (SHBG) is a glycoprotein which binds and controls the levels of sex-hormones within the circulation. Using a biosensor assay based on measurement of binding to an immobilised 1a-dihydrotestosterone (1a-DHT) derivative, reduced SHBG binding capacities were detected in growth-promoter treated animals. During the course of a veal treatment regime based on repeated oestradiol benzoate, nortestosterone decanoate and dexamethasone administrations, treated male and female calves were shown to have significantly lower SHBG capacities. To assess the effectiveness of using SHBG binding capacities as a biomarker of treatment and to investigate the role of individual growth-promoter components to the SHBG capacity lowering effects, adult heifer animals were subjected to repeated doses of nortestosterone decanoate. These animals also demonstrated a reduction in SHBG capacity levels at Day 39 of the study, in contrast to oestradiol benzoate treated adult steers who were found to have unaltered levels. These findings suggest that the measurement of SHBG binding capacities using a biosensor assay has potential in the identification of illegally treated animals, particularly those exposed to androgens.

‘Ulster Says No’: Regulating the consumption of commercial sex spaces and services in Northern Ireland

Commercial forms of sex such as prostitution/sex work, strip clubs and even sex shops have been the subject of much political debate and policy regulation over the last decade or so in the UK and Ireland. These myriad forms of commercial sex and land usage have managed to survive and even thrive in the face of public outcry and regulation. Despite being part of the UK we suggest that Northern Ireland has steered its own regulatory course, whereby the consumption of commercial sexual spaces and services have been the subject of intense moral and legal oversight in ways that are not apparent in other UK regions. Nevertheless, in spite of this we also argue that the context of Northern Ireland may provide some lessons for the ways that religious values and moral reasoning can influence debates on commercial sex elsewhere.

Sexual behaviour of young people in Northern Ireland: First sexual experience

Two National Surveys of Sexual Attitudes and Lifestyles in Britain (Natsal) were conducted, one in 1990 and one in 2000. Northern Ireland was excluded from both studies. Now, for the first time, comparable data about sexual attitudes and lifestyles of young people (14- to 25-year-olds) in Northern Ireland are available. Data were collected through self-administered questionnaires, one-to-one interviews and focus-group discussions. As in Natsal 1990 and 2000, young people were asked about their sexual attitudes towards sex, experiences of sex education, knowledge of sexually transmitted infections (STIs) and, if sexually active, about the circumstances in which sexual intercourse occurred. A total of 1013 young people in the target age group completed the self-administered questionnaire. Young people in Northern Ireland do not differ significantly from their counterparts in Britain in terms of sexual lifestyles and attitudes. Some 53.3% of all respondents reported that they had had sexual intercourse. Condom use at first sex was reported by 64% of sexually active respondents; 27.4% said they used no contraception; 26.7% of all respondents said they had sex before age 16. Respondents who first had sex when they were 15 or 16 years were more likely than other respondents to say that 'being drunk' was the main reason why intercourse occurred. Peer pressure to engage in sex was more prevalent among males than females. Young people in Northern Ireland regard friends as their most important source of sex education. School is the second most important source but most respondents wanted more sex education in school. It is important that it is needs focused and includes potentially sensitive and contentious information.

Spin asymmetries in spatially resolved processes of ionization of heavy atoms by relativistic electrons

The triple-differential cross section for ionization of a heavy atom is shown to depend on the spin of the incident electron even if this is polarized entirely parallel or antiparallel to its direction of propagation, the atom is unpolarized, and the spins of the ejected electrons are not resolved. Quantitative predictions for the spin asymmetry are presented in a relativistic distorted-wave Born approximation. Simple physical models are introduced to understand both these results and further symmetry properties involving the reversal of a spatial momentum component also.

Assembly intermediates in polyketide biosynthesis; enantioselective syntheses of beta-hydroxycarbonyl compounds

A versatile approach for the enantioselective synthesis of functionalised beta-hydroxy N-acetylcysteamine thiol esters has been developed which allows the facile incorporation of isotopic labels. It has been shown that a remarkable reversal of selectivity occurs in the titanium mediated aldol reaction of the acyloxazolidone intermediate using either (S)- or (R)-tert-butyldimethylsilyloxybutanal. The aldol products are valuable intermediates in the synthesis of 4-hydroxy-6-substituted gamma-lactones.

Org 25969 (sugammadex), a selective relaxant binding agent for antagonism of prolonged rocuronium-induced neuromuscular block

Background. Org 25969 is a cyclodextrin compound designed to reverse a rocuronium-induced neuromuscular block. The aim of this study was to explore the efficacy, dose-response relation and safety of Org 25969 for reversal of a prolonged rocuronium-induced neuromuscular block. Methods. Thirty anaesthetised adult patients received rocuronium 0.6mg kg as an initial dose followed by increments to maintain a deep block at level of

Neostigmine antagonism of rocuronium block during anesthesia with sevoflurane, isoflurane or propofol

Purpose: To examine the influence of continuing administration of sevoflurane or isoflurane during reversal of rocuronium induced neuromuscular block with neostigmine. Methods: One hundred and twenty patients, divided into three equal groups, were randomly allocated to maintenance of anesthesia with sevoflurane, isoflurane or propofol. Neuromuscular block was induced with rocuronium and monitored using train-of-four (TOF) stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. Neostigmine was administered when the first response in TOF had recovered to 25%. At this time the volatile agent administration was stopped or propofol dosage reduced in half the patients in each group (n = 20 in each group). The times to attain TOF ratio of 0.8, and the number of patients attaining this end point within 15 min were recorded. Results: The times (mean ± SD) to recovery of the TOF ratio to 0.8 were 12.0 ± 5.5 and 6.8 ± 2.3 min in the sevoflurane continued and sevoflurane stopped groups, 9.0 ± 8.3 and 5.5 ± 3.0 min in the isoflurane continued and isoflurane stopped groups, and 5.2 ± 2.8 and 4.7 ±1.5 min in the propofol continued and propofol stopped groups (P <0.5- 01). Only 9 and 15 patients in the sevoflurane and isoflurane continued groups respectively had attained a TOF ratio of 0.8 within 15 min (P <0.001 for sevoflurane). Conclusions: The continued administration of sevoflurane, and to a smaller extent isoflurane, results in delay in attaining adequate antagonism of rocuronium induced neuromuscular block.

Kir2.2 inward rectifier potassium channels are inhibited by an endogenous factor in Xenopus oocytes independently from the action of a mitochondrial uncoupler.

We previously showed inhibition of Kir2 inward rectifier K+ channels expressed in Xenopus oocytes by the mitochondrial agents carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) and sodium azide. Mutagenesis studies suggested that FCCP may act via phosphatidylinositol 4,5-bisphosphate (PIP2) depletion. This mechanism could be reversible in intact cells but not in excised membrane patches which preclude PIP2 regeneration. This prediction was tested by investigating the reversibility of the inhibition of Kir2.2 by FCCP in intact cells and excised patches. We also investigated the effect of FCCP on Kir2.2 expressed in human embryonic kidney (HEK) cells. Kir2.2 current, expressed in Xenopus oocytes, increased in inside-out patches from FCCP-treated and untreated oocytes. The fraction of total current that increased was 0.79?±?0.05 in control and 0.89?±?0.03 in 10 µM FCCP-treated (P?>?.05). Following “run-up,” Kir2.2 current was re-inhibited by “cramming” inside-out patches into oocytes. Therefore, run-up reflected not reversal of inhibition by FCCP, but washout of an endogenous inhibitor. Kir2.2 current recovered in intact oocytes within 26.5 h of FCCP removal. Injection of oocytes with 0.1 U apyrase completely depleted ATP (P?<?.001) but did not inhibit Kir2.2 and inhibited Kir2.1 by 35% (P?<?.05). FCCP only partially reduced [ATP] (P?<?.001), despite inhibiting Kir2.2 by 75% (P?<?.01) but not Kir2.1. FCCP inhibited Kir2.2 expressed in HEK cells. The recovery of Kir2.2 from inhibition by FCCP requires intracellular components, but direct depletion of ATP does not reproduce the differential inhibitory effect of FCCP. Inhibition of Kir2.2 by FCCP is not unique to Xenopus oocytes. J. Cell. Physiol. 219: 8–13, 2009. © 2008 Wiley-Liss, Inc.

Restorative Justice as a Response to Sexual Offending – Addressing the Failings of Current Punitive Approaches

This article explores the use of restorative justice as a response to sexual crime. The management of high risk sex offenders, particularly in the community post-release, has been a key focus of contemporary popular and political debates on sexual offending. Many offenders fail to come to the attention of the criminal justice system. For those that do, there is the almost blanket application of recent control in the community measures such as sex offender registries and community notification which have failed to prevent reoffending. The response by the media and the public to the presence of sex offenders in the community may also impede offender rehabilitation. The use of punishment alone via formal criminal justice is, therefore, an inadequate deterrent for sexual crimes. Although controversial, this article advocates the use of restorative practices with sexual crime as a proactive, holistic response to the problem and ultimately as a more effective means of reducing the incidence of sexual offences and sex offender recidivism.

Sex differences in responsiveness to begging in a cooperative mammal

In species where young are provisioned by both parents, males commonly contribute less to parental care than females, and are less responsive to variation in begging rates. Similar differences in the care of young occur among adults in cooperative breeders, but fewer studies have investigated whether these are associated with differences in responsiveness. Here, we present results from a playback experiment investigating responsiveness to begging in the meerkat (Suricata suricatta), a cooperatively breeding mammal. Although increased begging rate raised the feeding rate of adults of both sexes, there was no consistent tendency for females to be more responsive than males. However, when we examined changes in the proportion of food items found that were fed to pups (generosity), we found that females were more responsive than males to increased begging rate. These results can be explained in terms of sex differences in dispersal: in meerkats, females are philopatric and receive considerable benefits from investing in young, both directly, by increasing group size, and indirectly, by recruiting helpers if they inherit the breeding position. In addition, they emphasize that generosity provides a more sensitive measure of responsiveness to begging than feeding rate, as it accounts for variation in foraging success. © 2008 The Royal Society.

Tackling antibiotic resistance: a dose of common antisense?

Resistance to antimicrobial agents undermines our ability to treat bacterial infections. It attracts intense media and political interest and impacts on personal health and costs to health infrastructures. Bacteria have developed resistance to all licensed antibacterial agents, and their ability to become resistant to unlicensed agents is often demonstrated during the development process. Conventional approaches to antimicrobial development, involving modification of existing agents or production of synthetic derivatives, are unlikely to deliver the range or type of drugs that will be needed to meet all future requirements. Although many companies are seeking novel targets, further radical approaches to both antimicrobial design and the reversal of resistance are now urgently required. In this article, we discuss ‘antisense’ (or ‘antigene’) strategies to inhibit resistance mechanisms at the genetic level. These offer an innovative approach to a global problem and could be used to restore the efficacy of clinically proven agents. Moreover, this strategy has the potential to overcome critical resistances, not only in the so-called ‘superbugs’ (methicillin-resistant Staphylococcus aureus, glycopeptide-resistant enterococci and multidrug-resistant strains of Acinetobacter baumannii, and Pseudomonas aeruginosa), but in resistant strains of any bacterial species.

The genetics of coronary heart disease: The contribution of twin studies

Despite the decline in coronary heart disease in many European countries, the disease remains an enormous public health problem. Although we know a great deal about environmental risk factors for coronary heart disease, a heritable component was recognized a long time ago. The earliest and best known examples of how our genetic constitution may determine cardiovascular risk relate to lipoprotein(a), familial hypercholesterolaemia and apolipoprotein E. In the past 20 years a fair number of polymorphisms assessed singly have shown strong associations with the disease but most are subject to poor repeatability. Twins constitute a compelling natural experiment to establish the genetic contribution to coronary heart disease and its risk factors. GenomEUtwin, a recently funded Framework 5 Programme of the European Community, affords the opportunity of comparing the heritability of risk factors in different European Twin Registries. As an illustration we present the heritabilities of systolic and diastolic blood pressure, based on data from over 4000 twin pairs from six different European countries and Australia. Heritabilities for systolic blood pressure are between 52 and 66% and for diastolic blood pressure between 44 and 66%. There is no evidence of sex differences in heritability estimates and very little to no evidence for a significant contribution of shared family environment. A non-twin based prospective case/cohort study of coronary heart disease and stroke (MORGAM) will allow hypotheses relating to cardiovascular disease, generated in the twin cohorts, to be tested prospectively in adult populations. Twin studies have also contributed to our understanding of the life course hypothesis, and GenomEUtwin has the potential to add to this.

Managing Risk: From Regulation to the Reintegration of Sexual Offenders

In the last number of years the management of the dangerous in the community, particularly sex offenders, has generated enormous concern. This concern has been reflected at a number of different levels - in media and popular responses to the risk posed by released sex offenders in the community and in official discourses where an abundance of legislation and policy reforms have been enacted within a relatively short period of time. This analysis seeks to critically evaluate these developments within the context of contemporary criminal justice policy and practice in relation to the management of sex offenders in the community. The article analyses the contemporary focus on risk management or preventative governance which underpins the current regulatory framework and has been reflected in both the sentencing options and in control in the community initiatives for sex offenders. In this respect, the article highlights the gap between policy and practice in terms of the effective risk management of sex offenders. Given the failure of the traditional justice system with respect to these types of offences, it will be argued that the retributive framework could usefully be supplemented by the theory and practice of reintegrative or restorative community justice, and public education in particular, in order to better manage the risk presented by sex offenders in the community.

Sex Offender Registration: Implications and Difficulties for Ireland

The aim of this paper is to explore the implications and difficulties of a system of sex offender registration for Northern Ireland and the Republic of Ireland. From the orthodox perspective, registration appears justified. Sexual offending has increased and this is used by the media to generate a ‘moral panic’. However, sexual offenders in the community have also been socially constructed in Ireland, as a problem requiring specific action, through Blumer’s (1971) developmental perspective. It is this perspective which most adequately explains the formulation of the legislation. Arguments expounded in favour of registration include the supposedly high recidivism among sex offenders, the inadequacy of supervision provisions and the resulting need to ‘track’ the offender for public protection. Yet, in practice there are a plethora of obstacles such as cost and inadequate policing resources, not considered at the time the legislation was being formulated, which may impede its effectiveness in aiding law enforcement and reduce it to symbolic significance only. Given these difficulties, it is argued that registration is not an appropriate response to the problem of released sexual offenders in Ireland. Rather, from the social constructionist perspective, it is suggested that it is better to ‘treat’ the sex offender through less formal and stringent means in the community away from the criminal justice process.