Behavioral and epigenetic consequences of oxytocin treatment at birth.

Oxytocin is used in approximately half of all births in the United States during labor induction and/or augmentation. However, the effects of maternal oxytocin administration on offspring development have not been fully characterized. Here, we used the socially monogamous prairie vole to examine the hypothesis that oxytocin exposure at birth can have long-term developmental consequences. Maternally administered oxytocin increased methylation of the oxytocin receptor (Oxtr) in the fetal brain. As adults, oxytocin-exposed voles were more gregarious, with increased alloparental caregiving toward pups and increased close social contact with other adults. Cross-fostering indicated that these effects were the result of direct action on the offspring, rather than indirect effects via postnatal changes in maternal behavior. Male oxytocin-exposed offspring had increased oxytocin receptor density and expression in the brain as adults. These results show that long-term effects of perinatal oxytocin may be mediated by an epigenetic mechanism

Prevalence and predictors of video game addiction: a study based on a national representative sample of gamers

Video gaming has become a popular leisure activity in many parts of the world, and an increasing number of empirical studies examine the small minority that appears to develop problems as a result of excessive gaming. This study investigated prevalence rates and predictors of video game addiction in a sample of gamers, randomly selected from the National Population Registry of Norway (N =3389). Results showed there were 1.4 % addicted gamers, 7.3 % problem gamers, 3.9 % engaged gamers, and 87.4 % normal gamers. Gender (being male) and age group (being young) were positively associated with addicted-, problem-, and engaged gamers. Place of birth (Africa, Asia, South- and Middle America) were positively associated with addicted- and problem gamers. Video game addiction was negatively associated with conscientiousness and positively associated with neuroticism. Poor psychosomatic health was positively associated with problem- and engaged gaming. These factors provide insight into the field of video game addiction, and may help to provide guidance as to how individuals that are at risk of becoming addicted gamers can be identified

A genome-wide association study to identify genetic markers associated with endometrial cancer grade

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Synthetic Lethality of Chk1 Inhibition Combined with p53 and/or p21 Loss During a DNA Damage Response in Normal and Tumor Cells

Cell cycle checkpoints ensure genome integrity and are frequently compromised in human cancers. A therapeutic strategy being explored takes advantage of checkpoint defects in p53-deficient tumors in order to sensitize them to DNA-damaging agents by eliminating Chk1-mediated checkpoint responses. Using mouse models, we demonstrated that p21 is a key determinant of how cells respond to the combination of DNA damage and Chk1 inhibition (combination therapy) in normal cells as well as in tumors. Loss of p21 sensitized normal cells to the combination therapy much more than did p53 loss and the enhanced lethality was partially blocked by CDK inhibition. In addition, basal pools of p21 (p53 independent) provided p53 null cells with protection from the combination therapy. Our results uncover a novel p53-independent function for p21 in protecting cells from the lethal effects of DNA damage followed by Chk1 inhibition. As p21 levels are low in a significant fraction of colorectal tumors, they are predicted to be particularly sensitive to the combination therapy. Results reported in this study support this prediction

Entomological Surveillance of Behavioural Resilience and Resistance in Residual Malaria Vector Populations.

The most potent malaria vectors rely heavily upon human blood so they are vulnerable to attack with insecticide-treated nets (ITNs) and indoor residual spraying (IRS) within houses. Mosquito taxa that can avoid feeding or resting indoors, or by obtaining blood from animals, mediate a growing proportion of the dwindling transmission that persists as ITNs and IRS are scaled up. Increasing frequency of behavioural evasion traits within persisting residual vector systems usually reflect the successful suppression of the most potent and vulnerable vector taxa by IRS or ITNs, rather than their failure. Many of the commonly observed changes in mosquito behavioural patterns following intervention scale-up may well be explained by modified taxonomic composition and expression of phenotypically plastic behavioural preferences, rather than altered innate preferences of individuals or populations. Detailed review of the contemporary evidence base does not yet provide any clear-cut example of true behavioural resistance and is, therefore, consistent with the hypothesis presented. Caution should be exercised before over-interpreting most existing reports of increased frequency of behavioural traits which enable mosquitoes to evade fatal contact with insecticides: this may simply be the result of suppressing the most behaviourally vulnerable of the vector taxa that constituted the original transmission system. Mosquito taxa which have always exhibited such evasive traits may be more accurately described as behaviourally resilient, rather than resistant. Ongoing national or regional entomological monitoring surveys of physiological susceptibility to insecticides should be supplemented with biologically and epidemiologically meaningfully estimates of malaria vector population dynamics and the behavioural phenotypes that determine intervention impact, in order to design, select, evaluate and optimize the implementation of vector control measures

Impaired decisional impulsivity in pathological videogamers

Abstract Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment. Results In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time. Conclusions We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management

Expanding student teachers’ implicit theories about explanations for the science classrooms

This study explored student teachers’ implicit theories about explaining for the science classroom in three courses at diverse universities. Based on microteaching situations, the participants simulated explanations and discussed the elements they considered relevant for giving peer feedback. This led to the design of rubrics for peer assessment, which expressed their implicit theories about what a good explanation for the science classroom would look like. The three rubrics are presented and discussed in the light of the connections between teachers’ thinking and practice. Shulman’s ideas about professional teaching knowledge development, as well as negotiation of meaning, provide theoretical under-pinning for understanding and expanding student teachers’ thinking about explanations for the science classrooms.</p

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

"Give me some space" : exploring youth to parent aggression and violence

A small scale qualitative project, undertaken by an interdisciplinary domestic violence research group involving academic researchers and research assistants, with colleagues from Independent Domestic Abuse Services (IDAS), investigated youth aggression and violence against parents. Following the literature review, data was generated through several research conversations with young people (n = 2), through semi-structured interviews with mothers (n = 3) and practitioners (n = 5), and through a practitioner focus group (n = 8). Thematic analysis and triangulation of the data from parents, practitioners and young people, elicited interconnected and complex overarching themes. Young people could be both victim and perpetrator. The witnessing or experiencing of domestic aggression and violence raised the concept of ‘bystander children’. The impact of young people experiencing familial violence was underestimated by parents. For practitioners, the effects of working with domestic violence was shown to be significant - both positively and negatively

Suv4-20h Histone Methyltransferases Promote Neuroectodermal Differentiation by Silencing the Pluripotency-Associated Oct-25 Gene

Post-translational modifications (PTMs) of histones exert fundamental roles in regulating gene expression. During development, groups of PTMs are constrained by unknown mechanisms into combinatorial patterns, which facilitate transitions from uncommitted embryonic cells into differentiated somatic cell lineages. Repressive histone modifications such as H3K9me3 or H3K27me3 have been investigated in detail, but the role of H4K20me3 in development is currently unknown. Here we show that Xenopus laevis Suv4-20h1 and h2 histone methyltransferases (HMTases) are essential for induction and differentiation of the neuroectoderm. Morpholino-mediated knockdown of the two HMTases leads to a selective and specific downregulation of genes controlling neural induction, thereby effectively blocking differentiation of the neuroectoderm. Global transcriptome analysis supports the notion that these effects arise from the transcriptional deregulation of specific genes rather than widespread, pleiotropic effects. Interestingly, morphant embryos fail to repress the Oct4-related Xenopus gene Oct-25. We validate Oct-25 as a direct target of xSu4-20h enzyme mediated gene repression, showing by chromatin immunoprecipitaton that it is decorated with the H4K20me3 mark downstream of the promoter in normal, but not in double-morphant, embryos. Since knockdown of Oct-25 protein significantly rescues the neural differentiation defect in xSuv4-20h double-morphant embryos, we conclude that the epistatic relationship between Suv4-20h enzymes and Oct-25 controls the transit from pluripotent to differentiation-competent neural cells. Consistent with these results in Xenopus, murine Suv4-20h1/h2 double-knockout embryonic stem (DKO ES) cells exhibit increased Oct4 protein levels before and during EB formation, and reveal a compromised and biased capacity for in vitro differentiation, when compared to normal ES cells. Together, these results suggest a regulatory mechanism, conserved between amphibians and mammals, in which H4K20me3-dependent restriction of specific POU-V genes directs cell fate decisions, when embryonic cells exit the pluripotent state