Interleukin 3 and schizophrenia:the impact of sex and family history

Chromosome 5q21-33 has been implicated in harboring risk genes for schizophrenia. In this paper, we report evidence that multiple single nucleotide polymorphisms in and around interleukin 3 (IL3) are associated with the disease in the Irish Study of High-Density Schizophrenia Families (ISHDSF), the Irish Case-Control Study of Schizophrenia (ICCSS) and the Irish Trio Study of Schizophrenia (ITRIO). The associations are sex-specific and depend on the family history (FH) of schizophrenia. In all three samples, rs31400 shows female-specific and FH-dependent associations (P=0.0062, 0.0647 and 0.0284 for the ISHDSF, ICCSS and ITRIO, respectively). Several markers have similar associations in one or two of the three samples. In haplotype analyses, identical risk and protective haplotypes are identified in the ISHDSF and ITRIO samples in several multimarker combinations. For ICCSS, the same haplotypes are implicated; however, the risk haplotypes observed in the family samples become protective. Several significant markers, rs440970, rs31400 and rs2069803, are located in and around known estrogen response elements, promoter and enhancer of the IL3 gene. They may explain the sex-specific associations and be functional for the expression of IL3 gene.

The Reintegration of Sex Offenders: Barriers and Opportunities for Employment

The process of reintegration of offenders after release from prison, or during a community sentence, is a key aim of criminal justice policy. This article provides details from recent research that investigated the barriers and opportunities to employment for sex offenders. The authors describe the barriers that are faced by sex offenders and the anxieties that employers experience when employing sex offenders. The authors conclude that the approach taken by the State is less than reintegrative and serves to increase the barriers and reduce the opportunities for employment for sex offenders.

Sex hormone binding globulin and insulin resistance

Sex hormone binding globulin (SHBG) is a glycoprotein composed of two 373-amino-acid subunits. The SHBG gene and a promotor region have been identified. The SHBG receptor has yet to be cloned but is known to act through a G-protein-linked second-messenger system following plasma membrane binding. The principal function of SHBG has traditionally been considered to be that of a transport protein for sex steroids, regulating circulating concentrations of free (unbound) hormones and their transport to target tissues. Recent research suggests that SHBG has functions in addition to the binding and transport of sex steroids. Observational studies have associated a low SHBG concentration with an increased incidence of type 2 diabetes mellitus (DM) independent of sex hormone levels in men and women. Genetic studies using Mendelian randomization analysis linking three single nucleotide polymorphisms of the SHBG gene to risk of developing type 2 DM suggest SHBG may have a role in the pathogenesis of type 2 DM. The correlation between SHBG and insulin resistance that is evident in a number of cross-sectional studies is in keeping with the suggestion that the association between SHBG and incidence of type 2 DM is explained by insulin resistance. Several potential mechanisms may account for this association, including the identification of dietary factors that influence SHBG gene transcription. Further research to characterize the SHBG-receptor and the SHBG second messenger system is required. An interventional study examining the effects on insulin resistance of altering SHBG concentrations may help in determining whether this association is causal.

Sex equality law after Kalanke and Marschall

In Marschall, the ECJ looked for the second time into the admissibility of positive action in German public services; a third reference on this issue is still pending.
Despite the Court’s positive response to the ‘women’s quota’ in Marschall, its application in Germany remains controversial. This article tries to shed some light on the specific conditions under which women’s quotas were implemented in Germany and on the different approaches to anti-discrimination, indirect discrimination law and structural discrimination, which underlie efforts to justify women’s quotas against equality standards derived from EC Law.

Restorative Justice and Sex Offending

This essay examines the origins and uses of restorative justice with sexual offending and the contemporary challenges and controversies surrounding this. It charts the range of ad hoc initiatives which have sought to apply a restorative form of intervention with violent or sexual offending from first time and ‘acquaintance’ rape as well as young sexual abusers to high risk sexual offenders in the form of circles of support and accountability. Such schemes are often presented as a counter to the failings of retributive forms of justice and are premised on Braithwaite’s (1989) notion of ‘reintegrative shaming’ that seek to reintegrate offenders into the community. Critics of restorative justice traditionally put forward a number of core objectives when restorative justice is applied to serious forms of offending such as sexual offending. The essay also sets out and seeks to counter these principal challenges and how they may be overcome. For the most part, however, restorative justice has failed to reach its potential as a fully fledged sentencing rationale in being applied as a mainstream response to a wide range of offending including that at the higher end of the spectrum. The essay also seeks to examine barriers to restorative justice within contemporary penal policy and to highlight some of the most controversial applications of the restorative paradigm including those related to clergy sexual abuse. It concludes by offering some thoughts on the future of restorative justice as a mainstream responses to serious forms of offending.

In utero exposure to cigarette chemicals induces sex-specific disruption of one-carbon metabolism and DNA methylation in the human fetal liver

Background: Maternal smoking is one of the most important modifiable risk factors for low birthweight, which is strongly associated with increased cardiometabolic disease risk in adulthood. Maternal smoking reduces the levels of the methyl donor vitamin B12 and is associated with altered DNA methylation at birth. Altered DNA methylation may be an important mechanism underlying increased disease susceptibility; however, the extent to which this can be induced in the developing fetus is unknown.

Methods: In this retrospective study, we measured concentrations of cobalt, vitamin B12, and mRNA transcripts encoding key enzymes in the 1-carbon cycle in 55 fetal human livers obtained from 11 to 21 weeks of gestation elective terminations and matched for gestation and maternal smoking. DNA methylation was measured at critical regions known to be susceptible to the in utero environment. Homocysteine concentrations were analyzed in plasma from 60 fetuses.

Results: In addition to identifying baseline sex differences, we found that maternal smoking was associated with sex-specific alterations of fetal liver vitamin B12, plasma homocysteine and expression of enzymes in the 1-carbon cycle in fetal liver. In the majority of the measured parameters which showed a sex difference, maternal smoking reduced the magnitude of that difference. Maternal smoking also altered DNA methylation at the imprinted gene IGF2 and the glucocorticoid receptor (GR/NR3C1).

Conclusions: Our unique data strengthen studies linking in utero exposures to altered DNA methylation by showing, for the first time, that such changes are present in fetal life and in a key metabolic target tissue, human fetal liver. Furthermore, these data propose a novel mechanism by which such changes are induced, namely through alterations in methyl donor availability and changes in 1-carbon metabolism.