Multilevel Deconstruction of the In Vivo Behavior of Looped DNA-Protein Complexes

Protein-DNA complexes with loops play a fundamental role in a wide variety of cellular processes, ranging from the regulation of DNA transcription to telomere maintenance. As ubiquitous as they are, their precise in vivo properties and their integration into the cellular function still remain largely unexplored. Here, we present a multilevel approach that efficiently connects in both directions molecular properties with cell physiology and use it to characterize the molecular properties of the looped DNA-lac repressor complex while functioning in vivo. The properties we uncover include the presence of two representative conformations of the complex, the stabilization of one conformation by DNA architectural proteins, and precise values of the underlying twisting elastic constants and bending free energies. Incorporation of all this molecular information into gene-regulation models reveals an unprecedented versatility of looped DNA-protein complexes at shaping the properties of gene expression.Comment: Open Access article available at http://www.plosone.org/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.000035

Cervical cytological changes in HIV-infected patients attending care and treatment clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania

\ud Tanzania is among Sub-Saharan countries mostly affected by the HIV and AIDS pandemic, females being more vulnerable than males. HIV infected women appear to have a higher rate of persistent infection by high risk types of human papillomavirus (HPV) strongly associated with high-grade squamous intraepithelial lesions (HSIL) and invasive cervical carcinoma. Furthermore, although HIV infection and cervical cancer are major public health problems, the frequency and HIV/HPV association of cervical cancer and HSIL is not well documented in Tanzania, thus limiting the development of preventive and therapeutic strategies. A prospective unmatched, case-control study of HIV-seropositive, ≥ 18 years of age and consenting non-pregnant patients attending the care and treatment center (CTC) at Muhimbili National Hoospital (MNH) as cases was done between 2005 and 2006. HIV seronegative, non-pregnant and consenting women recruited from the Cervical Cancer Screening unit (CCSU) at ORCI were used as controls while those who did not consent to study participation and/or individuals under < 18 years were excluded. Pap smears were collected for routine cytodiagnosis and P53 immunohistochemistry (IHC). Cervical lesions were classified according to the Modified Bethesda System. A total of 170 participants from the two centers were recruited including 50 HIV-seronegative controls were from the CCSU. Ages ranged from 20-66 years (mean 40.5 years) for cases and 20-69 years (mean 41.6 years) for controls. The age group 36-45 years was the most affected by HIV (39.2%, n = 47). Cervicitis, squamous intraepithelial lesions (SIL) and carcinoma constituted 28.3% (n = 34), 38.3% (n = 46) and 5.8% (n = 7) respectively among cases, and 28% (n = 14), 34% (n = 17) and 2% (n = 1) for controls, although this was not statistically significant (P-value = 0.61). IHC showed that p53 was not detectable in HPV + Pap smears and cell blocks indicating possible degradation. The frequency of SIL and carcinoma appeared to be higher among HIV-infected women on HAART compared to seronegative controls and as expected increased with age. HIV seropositive patients appeared to present earlier with SIL compared to those HIV seronegative suggesting a role of HIV in altering the natural history of HPV infection and cervical lesions. The absence of p53 immunoreactivity in HPV + lesions is indicative of the ability of HPV E6 proteins to interact with the tumor suppressor gene and pave way for viral-induced oncogenesis in the studied Tanzanian women.\u

Interventions for psychosexual dysfunction in women treated for gynaecological malignancy

Backgroun

Cerebral activations during viewing of food stimuli in adult patients with acquired structural hypothalamic damage: A functional neuroimaging study

BACKGROUND/OBJECTIVES: Obesity is common following hypothalamic damage due to tumours. Homeostatic and non-homeostatic brain centres control appetite and energy balance but their interaction in the presence of hypothalamic damage remains unknown. We hypothesized that abnormal appetite in obese patients with hypothalamic damage results from aberrant brain processing of food stimuli. We sought to establish differences in activation of brain food motivation and reward neurocircuitry in patients with hypothalamic obesity (HO) compared with patients with hypothalamic damage whose weight had remained stable. SUBJECTS/METHODS: In a cross-sectional study at a University Clinical Research Centre, we studied 9 patients with HO, 10 age-matched obese controls, 7 patients who remained weight-stable following hypothalamic insult (HWS) and 10 non-obese controls. Functional magnetic resonance imaging was performed in the fasted state, 1 h and 3 h after a test meal, while subjects were presented with images of high-calorie foods, low-calorie foods and non-food objects. Insulin, glucagon-like peptide-1, Peptide YY and ghrelin were measured throughout the experiment, and appetite ratings were recorded. RESULTS: Mean neural activation in the posterior insula and lingual gyrus (brain areas linked to food motivation and reward value of food) in HWS were significantly lower than in the other three groups (P=0.001). A significant negative correlation was found between insulin levels and posterior insula activation (P=0.002). CONCLUSIONS: Neural pathways associated with food motivation and reward-related behaviour, and the influence of insulin on their activation may be involved in the pathophysiology of HO.International Journal of Obesity advance online publicatio

Sexual dysfunction among married couples living in Kumasi metropolis, Ghana

<p>Abstract</p> <p>Background</p> <p>Sexuality and its manifestation constitute some of the most complex of human behaviour and its disorders are encountered in community. Sexual dysfunction is more prevalent in women than in men. While studies examining sexual dysfunction among males and females in Ghana exist, there are no studies relating sexual problems in males and females as dyadic units. This study therefore investigated the prevalence and type of sexual disorders among married couples.</p> <p>Method</p> <p>The study participants consisted of married couples between the ages of 19 and 66 living in the province of Kumasi, Ghana. Socio-demographic information and Golombok-Rust Inventory of Sexual Satisfaction (GRISS) questionnaires were administered to 200 couples who consented to take part in the study. All 28 questions of the GRISS are answered on a five-point (Likert type) scale from "always", through "usually', "sometimes", and "hardly ever", to "never". Responses are summed up to give a total raw score ranging from 28-140. The total score and subscale scores are transformed using a standard nine point scale, with high scores indicating greater problems. Scores of five or more are considered to indicate SD. The study was conducted between July and September 2010.</p> <p>Results</p> <p>Out of a total of 200 married couples, 179 completed their questionnaires resulting in a response rate of 89.5%. The mean age of the participating couples as well as the mean duration of marriage was 34.8 ± 8.6 years and 7.8 ± 7.6 years respectively. The husbands (37.1 ± 8.6) were significantly older (p < 0.0001) than their corresponding wives (32.5 ± 7.9). After adjusting for age, 13-18 years of marriage life poses about 10 times significant risk of developing SD compared to 1-6 years of married life among the wives (OR: 10.8; CI: 1.1 - 49.1; p = 0.04). The total scores (6.0) as well as the percentage above the cut-off (59.2) obtained by the husbands compared to the total score (6.2) and the percentage above cut-off (61.5) obtained by the wives, indicates the likely presence of sexual dysfunction. The prevalence of impotence and premature ejaculation were 60.9% and 65.4% respectively from this study and the prevalence of vaginismus and anorgasmia were 69.3% and 74.9% respectively. The highest prevalence of SD subscales among the men was dissatisfaction with sexual act followed by infrequency, whereas the highest among the women was infrequency followed by anorgasmia. Dissatisfaction with sexual intercourse among men correlated positively with anorgasmia and wife's non-sensuality and infrequency of sex.</p> <p>Conclusion</p> <p>The prevalence of sexual dysfunction in married couples is comparable to prevalence rates in the general male and female population and is further worsened by duration of marriage. This could impact significantly on a couple's self-esteem and overall quality of life.</p

BMC Public Health

BACKGROUND: In 2009, the World Health Organization's Commission on Social Determinants of Health set out its recommendations for action, which included establishing equity from early childhood onwards by enabling all children and their mothers to benefit from a comprehensive package of quality programmes. In order to address social inequalities in health, it is recommended that action be taken from early childhood, and actions providing support for parenting are an effective lever in this respect. The aim of this review of systematic reviews is to analyse, on the one hand, the components and characteristics of effective interventions in parenting support and, on the other, the extent to which the reviews took into account social inequalities in health. METHODS: A total of 796 reviews were selected from peer-reviewed journals published between 2009 and 2016 in French or English. Of these, 21 reviews responding to the AMSTAR and selected ROBIS criteria were retained. These were analysed in relation to the consideration they gave to social inequalities in health according to PRISMA-equity. RESULTS: The reviews confirmed that parenting support programmes improved infants' sleep, increased mothers' self-esteem and reduced mothers' anger, anxiety and stress levels. The mainly authors noted that the contexts in which the interventions had taken place were described either scantly or not at all, making it difficult to evaluate them. Only half of the reviews had addressed the question of social inequalities in health. In particular, there had been little research conducted on the relational aspect and the social link. CONCLUSION: In terms of addressing social inequalities in perinatal health, the approach remains both modest and reductive. Understanding how, for whom and in what conditions interventions operate is one way of optimising their results. Further research is needed to study the interactions between the interventions and their contexts

The ongoing evolution of behavioral couples therapy: Retrospect and prospect

Behavioral couples therapy (BCT) was first described thirty years ago, and the conceptual basis of the approach has been evolving ever since. Whilst BCT in its current form is a well established treatment for relationship problems, there are significant limitations to its efficacy, and there are a number of new developments intended to enhance the efficacy of the approach. Currently BCT primarily is a skills training therapy, targeting change in couple's interactions to promote greater relationship satisfaction. Current developments focus on broadening this traditional emphasis on changing couple interactions to greater attention to reducing negative emotional responses to partner behaviors (increasing acceptance), and increasing self-directed personal change efforts. Future developments of BCT are likely to pay greater attention to different types of couple interaction which are associated with sustained relationship satisfaction, the individual vulnerabilities partners bring to relationships, and the environmental stresses impinging upon the couple. (C) 1998 Elsevier Science Ltd

Behavior-Therapy and Schizophrenia - An Introduction

This brief article introduces a two-part series of special issues of Behaviour Change on the cognitive-behavioural treatment of schizophrenia. Two pervasive myths about schizophrenia inhibit effective psychological treatment and rehabilitation: (1) that schizophrenia inevitably has poor outcome, and (2) that drugs are effective in the management of schizophrenia. Neither of these myths is supported by available data. A stress-vulnerability model is described which provides a framework for understanding the variability in outcome of schizophrenia, and for conducting cognitive-behaviour therapy

Empirically validated psychological treatment: What does it mean in the domain of relationship problems?

The concept of empirically validated treatments is an attempt to focus psychological training and practice on treatments that work. In this paper, I examine the complexities of defining the concept with reference to the treatment of relationship problems. The key criterion employed to define a treatment as empirically validated is established efficacy within controlled trials. I suggest that the criteria need to be expanded to include assessment of the variability, clinical significance, and durability of treatment effects, the relative efficacy of alternative approaches, and the ease of dissemination of treatments. Whilst few, if any, psychological treatments currently have data on whether they meet all these criteria, I suggest that setting these more ambitious criteria will direct us towards the ultimate goal of offering better psychological treatments