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PubMed2000

Identification of multiple proteins expressed in murine embryos as binding partners for the WW domains of the ubiquitin-protein ligase Nedd4.

Nedd4 is a member of a growing family of ubiquitin-protein ligases which consist of a lipid-binding domain, two to four WW domains and a C-terminal ubiquitin-protein ligase domain. The Nedd4 mRNA levels are developmentally regulated and Nedd4 protein is highly expressed in many mouse embryonic tissues. In this study we have used a far-Western screen to identify embryonic proteins that interact with the WW domains in mouse Nedd4. We report here identification of eight Nedd4 WW-domain-interacting proteins from mouse embryonic cDNA expression libraries. Two of the proteins are novel, while two have been identified previously as ligands for a WW domain. All of these proteins contain one or more PY motifs. In seven of the eight proteins, these PY motifs are necessary for their interaction with the WW domains of Nedd4. Using site-directed mutagenesis, and by using individual WW domains of Nedd4 as probes for far-Western analysis, we show that the three WW domains in Nedd4 interact with varying affinities with the PY motifs present in various Nedd4-binding proteins. These results provide evidence that Nedd4 can potentially interact with multiple proteins, possibly simultaneously, through its WW domains.

Amino Acid Motifs↗
PubMed1996

Casual sex, extramarital sex, condom use and alcohol intake among heterosexual patients attending an STD clinic in Norway.

A study excluding homosexuals was performed to study casual sex, extramarital sex, the use of a condom with a casual sexual partner and the combination of alcohol intake and casual sex among patients attending a clinic for sexually transmitted diseases (STDs). Heterosexual patients (467) received a questionnaire, and 458 were included. Men reported more (94%) casual sexual partners than did women (76%). According to a multiple logistic regression analysis a condom was used significantly less frequently in "old" respondents, those having a permanent sexual partner, those having low education, those infected with STDs (earlier STDs), those who had had more than 4 sexual partners over the last year, and those combining alcohol intake and casual sex. Intravenous drug users/prostitutes used a condom more often than did men with paid sex and "other heterosexuals". To have an effect on STD patients, innovative forms of health education may be necessary, and greater emphasis should be placed on more informal means of information, including interactive health education and communication strategies to promote positive attitudes regarding condom use.

Adolescent↗
PubMed2006

The many faces of protein-protein interactions: A compendium of interface geometry.

A systematic classification of protein-protein interfaces is a valuable resource for understanding the principles of molecular recognition and for modelling protein complexes. Here, we present a classification of domain interfaces according to their geometry. Our new algorithm uses a hybrid approach of both sequential and structural features. The accuracy is evaluated on a hand-curated dataset of 416 interfaces. Our hybrid procedure achieves 83% precision and 95% recall, which improves the earlier sequence-based method by 5% on both terms. We classify virtually all domain interfaces of known structure, which results in nearly 6,000 distinct types of interfaces. In 40% of the cases, the interacting domain families associate in multiple orientations, suggesting that all the possible binding orientations need to be explored for modelling multidomain proteins and protein complexes. In general, hub proteins are shown to use distinct surface regions (multiple faces) for interactions with different partners. Our classification provides a convenient framework to query genuine gene fusion, which conserves binding orientation in both fused and separate forms. The result suggests that the binding orientations are not conserved in at least one-third of the gene fusion cases detected by a conventional sequence similarity search. We show that any evolutionary analysis on interfaces can be skewed by multiple binding orientations and multiple interaction partners. The taxonomic distribution of interface types suggests that ancient interfaces common to the three major kingdoms of life are enriched by symmetric homodimers. The classification results are online at http://www.scoppi.org.

Amino Acid Sequence↗
PubMed2003

Impact of recently diagnosed multiple sclerosis on quality of life, anxiety, depression and distress of patients and partners.

OBJECTIVES: Studies demonstrating reduced quality of life and psychological well-being in multiple sclerosis (MS) have typically investigated patients within more advanced stages of disease. The aim of the present paper was to evaluate the emotional burden and quality of life of recently diagnosed MS patients and their partners. METHODS: Data on health-related quality of life (SF-36), anxiety and depression (Hospital Anxiety and Depression Scale) and disease-related distress (Impact of Event Scale) were obtained in 101 patients and their partners (n=78). RESULTS: On average 8 months after diagnosis (range 0-24 months), 34% of the patients and 40% of the partners had clinically high levels of anxiety, and 36% of the patients and 24% of the partners had levels of severe distress. Scores of anxiety, depression and distress were higher in patients with more functional limitations (Expanded Disability Status Scale=3.0). Quality of life was significantly poorer in patients compared with controls, particularly among those with higher disability. CONCLUSIONS: Both patients and their partners demonstrated high levels of anxiety and distress in the early period after the diagnosis. These findings indicate careful attention by health care professionals to identify those who may benefit from further psychological support.

Adult↗
PubMed1991

Human immunodeficiency virus and migrant labor in South Africa.

The authors investigate the impact of the migrant labor system on heterosexual relationships on South African mines and assess the implications for the future transmission of human immunodeficiency virus (HIV) infection. The migrant labor system has created a market for prostitution in mining towns and geographic networks of relationships within and between urban and rural communities. A section of the migrant workforce and a group of women dependent on prostitution for economic support appear especially vulnerable to contracting HIV infection since they are involved in multiple sexual encounters with different, changing partners, usually without condom protection. Furthermore, sexually transmitted disease morbidity is extensive in the general and mineworker populations. Historically, migration facilitated the transmission of sexually transmitted diseases and may act similarly for HIV. Problems of combating the HIV epidemic in South Africa are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Conservation of orientation and sequence in protein domain--domain interactions.

The repertoire of naturally occurring protein structures is usually characterised in structural terms at the domain level by their constituent folds. As structure is acknowledged to be an important stepping stone to the understanding of protein function, an appreciation of how individual domain interactions are built to form complete, functional protein structures is essential. A comprehensive study of protein domain interactions has been undertaken, covering all those observed in known structures, as well as those predicted to occur in 46 completed genome sequences from all three domains of life. In particular, we examine the promiscuity of protein domains characterised by SCOP superfamilies in terms of their interacting partners, the surface they use to form these interactions, and the relative orientations of their domain partners. Protein domains are shown to display a variety of behaviours, ranging from high promiscuity to absolute monogamy of domain surface employed, with both multiple and single domain partners. In addition, the conservation of sequence and volume at domain interface surfaces is observed to be significantly higher than at accessible surface in general, acting as a powerful potential predictor for domain interactions. We also examine the separation of interacting domains in protein sequence, showing that standard thresholds of 30 amino acid residues lead to a significant false positive rate, and an even more significant false negative rate of approximately 40%. These data suggest that there may be many more than the 2000 domain--domain interactions that have not yet been observed structurally, and we provide a top 30 hit-list of putative domain interactions which should be targeted.

Amino Acid Motifs↗
PubMedDate not supplied

Lone motherhood and risk for cardiovascular disease: the National Population Health Survey (NPHS), 1998-99.

PURPOSE: To examine whether lone parenthood among Canadian women is associated with risk factors for cardiovascular disease (CVD). METHODS: The sample was from the National Population Health Survey (NPHS) and it included 2,184 mothers (women with dependent children < 18 years of age) of whom 478 were lone (22%) and 1,706 (78%) were partnered mothers. Descriptive statistics and multiple logistic regression were undertaken with weighted data. RESULTS: Compared to partnered mothers, lone mothers were significantly younger, and reported lower levels of education and income. Lone mothers reported significantly lower levels of health, less social support, and more distress and depression than partnered mothers. Further, lone mothers were significantly more likely to be smokers than partnered mothers. Odds ratios for being a lone mother and current smoker on social assistance in this analysis was 4.15 (95% CI 2.27-7.60), and for those reporting low or mid/high incomes respectively, were 2.99 (1.51-5.90) and 3.01 (1.93-4.70). There were no significant differences between the two groups for obesity or physical activity. CONCLUSIONS: Smoking is a significant CVD lifestyle risk for lone mothers. Smoking occurred in the context of considerable life stress, depression, and distress pointing to links between health behaviour, psychosocial factors, and CVD health. These results suggest that lone mothers are a key target group for primary prevention in the CVD field. Programs and policies that support lone mothers in their goals of attaining healthier lifestyles have the potential to contribute to the prevention of cardiovascular disease in Canadian women.

Adult↗
PubMed2001

Structural determinants outside the PXDLS sequence affect the interaction of adenovirus E1A, C-terminal interacting protein and Drosophila repressors with C-terminal binding protein.

C-Terminal binding protein (CtBP) interacts with a highly conserved amino acid motif (PXDLS) at the C terminus of adenovirus early region 1A (AdE1A) protein. This amino acid sequence has recently been demonstrated in the mammalian protein C-terminal interacting protein (CtIP) and a number of Drosophila repressors including Snail, Knirps and Hairy. In the study described here we have examined the structures of synthetic peptides identical to the CtBP binding sites on these proteins using NMR spectroscopy. It has been shown that peptides identical to the CtBP binding site in CtIP and at the N terminus of Snail form a series of beta-turns similar to those seen in AdE1A. The PXDLS motif towards the C terminus of Snail forms an alpha-helix. However, the motifs in Knirps and Hairy did not adopt well-defined structures in TFE/water mixtures as shown by the absence of medium range NOEs and a high proportion of signal overlap. The affinities of peptides for Drosophila and mammalian CtBP were compared using enzyme-linked immunosorbent assay. CtIP, Snail (N-terminal peptide) and Knirps peptides all bind to mammalian CtBP with high affinity (K(i) of 1.04, 1.34 and 0.52 microM, respectively). However, different effects were observed with dCtBP, most notably the affinity for the Snail (N-terminal peptide) and Knirps peptides were markedly reduced (K(i) of 332 and 56 microM, respectively) whilst the Hairy peptide bound much more strongly (K(i) for dCtBP of 6.22 compared to 133 microM for hCtBP). In addition we have shown that peptides containing identical PXDLS motifs but with different N and C terminal sequences have appreciably different affinities for mammalian CtBP and different structures in solution. We conclude that the factors governing the interactions of CtBPs with partner proteins are more complex than simple possession of the PXDLS motif. In particular the overall secondary structures and amino acid side chains in the binding sites of partner proteins are of importance as well as possible global structural effects in both members of the complex. These data are considered evidence for a multiplicity of CtBPs and partner proteins in the cell.

Adenovirus E1A Proteins↗
PubMed1998

Condom use among Aboriginal people in Ontario, Canada.

A survey of 658 Aboriginal men and women living in 11 reserve communities in Ontario, Canada, was utilized to collect data on patterns of condom use. Individuals who had sexual intercourse in the previous 12 months were included in the analysis (n=400). Descriptive statistics and multiple logistic regression were used to analyse condom use in the previous 12 months. Eight per cent always, 31% sometimes, and 61% never used condoms. Rates of condom use differed with the number of sex partners in the last year, age, gender, having a steady sex partner, and marital status. Multiple logistic regression revealed that people most likely to use condoms were under the age of 30, male, did not have a long-term steady sex partner, had more than one sex partner, worried about pregnancy, were knowledgeable about HIV/AIDS, and were not embarrassed to obtain condoms. Condom users who were knowledgeable about HIV/AIDS and who knew someone with HIV/AIDS were more likely to always use condoms. The most common reason for not using a condom was 'I was with my steady sex partner'. These results have implications for STD prevention efforts and for future research of sexual and STD preventive behaviour among Aboriginal people.

Adolescent↗
PubMedDate not supplied

Sexual partnership patterns as a behavioral risk factor for sexually transmitted diseases.

CONTEXT: Women's and men's number of sexual partners and protective practices such as condom use can have a direct effect on their risk of contracting sexually transmitted diseases (STDs), including HIV. METHODS: The 1988 and 1995 cycles of the National Survey of Family Growth and five rounds of the General Social Survey conducted from 1988 to 1996 are used to examine women's and men's numbers of recent sexual partners. Levels of direct risk for STDs (two or more partners in the past year) and the social and demographic correlates of multiple partnership are analyzed among women and men. In addition, women's indirect risk for STDs (their partners' involvement with other partners in the past year) is used to estimate their overall risk of STDs through multiple partnerships. RESULTS: At least three-quarters of sexually active U.S. women and men in the late 1980s and mid-1990s had had only one sexual partner in the preceding 12 months. Moreover, there is no indication that the proportion with more than one partner in the past year changed substantially over that period. Nevertheless, combining women's and men's partnership reports suggests that about 17 million women aged 15-44--34% of those sexually active in the past year--were at risk for STDs because of direct exposure to multiple partners (5.4 million), indirect exposure (6.3 million) or both direct and indirect exposure (5.5 million). In all, 21% of women were at direct risk and 23% were at indirect risk. In comparison, among men aged 18-44, 24% were at direct risk for STDs and an unknown proportion were at indirect risk. Multivariate analyses indicated that unmarried individuals, women younger than 40 and men aged 20-29, blacks and women in the South were all at elevated risk for STDs because of multiple partnership. Overall, in 1995, 19% of sexually active women aged 15-44 had used condoms to protect against STDs over the preceding year, and 19% of those sexually active in the three months before the survey were current condom users. Condom use specifically for STD prevention was more common among women reporting both direct and indirect risk for STDs (58%) and among those at direct risk (46%) than among other women; women whose partners put them at indirect risk only were less likely to be current or recent condom users than women who were not at risk or were only at direct risk. CONCLUSIONS: There is a continuing need to educate people regarding their risk for STDs, to increase the use of existing barrier methods and to develop new methods that protect against STD infection. In addition, if we are to develop a better understanding of the extent of STD risk through multiple partnership, the collection of information on number of partners and relationships between partners must be expanded and improved.

Adolescent↗
PubMed2005

Women's experience of intimate partner violence in Haiti.

This study examined individual, partner, and community characteristics associated with the occurrence of intimate partner violence among ever-married women of reproductive age, using data from the 2000 Haiti Demographic and Health Survey. Separate logistic regressions were analyzed to assess women's risks of experiencing emotional, physical and sexual violence and multiple forms of intimate partner violence in the past 12 months. Twenty-nine percent of women in the sample experienced some form of intimate partner violence in the past 12 months, with 13 percent having experienced at least two different forms of violence. Significant positive associations with all forms of violence were found for lack of completion of primary school, history of violence exposure in women's families of origin either through witnessing violence between parents while growing up or direct experience of physical violence perpetrated by family members, partner's jealousy, partner's need for control, partner's history of drunkenness, and female-dominated financial decision-making. Significant positive associations were found between men's physical abuse of children at the community level and women's risk of experiencing emotional and physical violence. Neighborhood poverty and male unemployment, number of children living at home, women's attitudinal acceptance of wife beating, and male-dominated financial decision-making were additional risk factors for sexual violence. Women's economic independence was a protective factor for emotional and physical violence, while relationship quality was protective for all forms of violence and multiple victimizations.

Adult↗
PubMed1989

Predictors of AIDS-preventive behavior among homosexually active men: a longitudinal study.

Predictors of adoption of safer sexual behaviors were examined in a cohort of 278 homosexually active men with stable HIV-antibody status followed over 12 months at a Boston community health center. The behaviors examined included: (1) restriction of partners to one monogamous or steady relationship and (2) among men who maintained multiple or non-steady partners, the avoidance of unprotected receptive and insertive anogenital contact. For each behavior, men who adopted consistently safer behavior were compared with those who remained unsafe, using bivariate analyses and multiple logistic regression modelling. The strongest predictor of all behaviors was the initial level of the unsafe behavior. After controlling for this, weak effects of several health beliefs were found, including perceived susceptibility and medical efficacy. Men who became aware of a positive HIV-antibody test result and who reported greater effort to change their behavior were more likely to adopt safer insertive anogenital contact. In this generally well-educated cohort with high levels of knowledge about AIDS, adoption of safer sexual behaviors is best predicted from previous levels of unsafe behavior.

Acquired Immunodeficiency Syndrome↗
PubMed2005

High HIV, hepatitis C and sexual risks among drug-using men who have sex with men in northern Thailand.

BACKGROUND: Men who have sex with men (MSM) and who use drugs have shown high HIV risks in Europe, and the Americas. We investigated MSM-drug user demographics, HIV sexual and drug use risks and behaviors in Chiang Mai, northern Thailand to identify prevention targets. METHODS: A total of 2005 males aged 13 years and older were enrolled during inpatient drug treatment from 1999-2000 and assessed for HIV, hepatitis C virus (HCV), syphilis, and for demographics and risks by questionnaire. Data were analyzed using chi and multiple logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of 2005 males in treatment, 1752 (87.4%) had ever had sex, and 66 of 1752 (3.8%) reported ever having sex with another man; mostly Katoey (transgendered male) partners. MSM had higher HIV rates (OR, 2.32; 95% CI, 1.36-3.96) and were younger (P = 0.002); more likely to be Thai (P < 0.0001); better educated (P < 0.0001); had more lifetime sex partners (P < 0.0001), more female partners (P = 0.002), more female paid partners (P < 0.0001), and been paid for sex (P < 0.0001). MSM were more likely to have ever injected (P < 0.0001), sold drugs, been in prison, injected in prison, used heroin, and to have HCV (OR, 2.59; 95% CI, 1.55-4.34). CONCLUSIONS: Northern Thai MSM-drug users are at high HIV and HCV risk. In addition to sex risks with men, they have more sex with women and sex workers than other men, which fits Thai MSM patterns but not Western ones. Prevention must take into account their high rates of substance use and multiple partner types.

Adolescent↗
PubMed1995

Fighting as a marker for multiple problem behaviors in adolescents.

PURPOSE: Behaviors that put adolescents at risk frequently occur together. To help identify high-risk adolescents, we analyzed a national, self-reported behavior survey of high school students to assess the suitability of fighting as a marker for students with multiple problem behaviors. METHODS: A cross-sectional cluster survey of 11,631 U.S. high school students in 1990 was used to compare the prevalence of recent problem behaviors among all students and those who fight. RESULTS: One (8%) of every 12 students was in a fight during the 30 days before the survey. Reported problem behaviors were prevalent among fighters: during the previous 12 months, 24% attempted suicide; during the previous 30 days, 26% carried a firearm, 13% used cocaine, and 39% drove a motor vehicle while intoxicated; during the previous 3 months 41% had two or more sex partners; and 45% had sexual intercourse and did not use a condom the last time they had sex. Of all students, fighters accounted for 22% of those who reported attempting suicide, 49% carrying a firearm, 46% using cocaine, 18% driving while intoxicated, 25% having sex with multiple partners, and 11% not using condoms. Three or more of these six problem behaviors were reported by 26% of the fighters. The problem behaviors were all positively correlated, and the first principal component accounted for 35% of the total variation among the individual variables.

Adolescent↗
PubMed1993

Heterosexual transmission of HIV in a cohort of couples in New York City.

OBJECTIVE: Since heterosexual transmission of HIV in the United States is occurring at an increasing rate, especially among black and Hispanic couples and those in which one member has a history of intravenous drug use, we sought to study the heterosexual transmission of HIV in couples. DESIGN: Multiple logistic regression analysis of risks for HIV infection in female partners. METHODS: We enrolled 158 non-intravenous drug user (IVDU) steady heterosexual partners of HIV-infected individuals (indexes) in this study. Of these, 93% were women, 54% were Hispanic whites, 23% were black and 65.6% were partners of IVDU. RESULTS: In a multiple logistic regression analysis of risks for HIV infection in female partners, the strongest predictors of transmission were AIDS or AIDS-related complex (ARC) in the index [adjusted odds ratios (OR), 16.81; P < 0.001 and 12.53; P = 0.003, respectively], a history of anal intercourse (adjusted OR, 10.81; P < 0.001) and bleeding as a result of intercourse (adjusted OR, 4.90; P < 0.05). Female-to-male transmission was detected in seven out of 11 couples at risk. Ethnicity, number of episodes of vaginal intercourse, number of other sexual partners and history of sexually transmitted infections were not significantly associated with transmission to women. CONCLUSION: Our study demonstrates that health of the index, anal intercourse and bleeding as a result of intercourse are the major determinants of sexual transmission of HIV to women in couples.

Adolescent↗
PubMed2006

Sexual behavior among men who have sex with women, men, and Hijras in Mumbai, India--multiple sexual risks.

We describe the same-sex partnerships and sexual risk behavior of men attending sexually transmitted infection (STI) clinics in Mumbai, India. The HIV prevalence among 2,381 men sampled was 14%; 62% had a documented STI. Almost all men reported sex with women; additionally, 13% also reported having sex with other men, 13% reported sex with Hijras (male-to-female transgenders), and 11% had sex with all 3 genders. Men who had sex with men and/or Hijras as well as women, reported having greater numbers of partners, including female sex workers (FSW), and were more likely to engage in insertive anal and oral sex with women. The prevalence of HIV was higher among men having sex with Hijras (14%) or with all 3 genders (13%) than among men having sex with men and women (8%). A high proportion of men who attend STI clinics in Mumbai are behaviorally bi- or tri-sexual and have multiple partners with whom they engage in risky sex. STI/HIV prevention programs should not assume that men only have sex with women.

Adolescent↗
PubMed1995

Differences in HIV risk characteristics between bisexual and exclusively gay men.

Research investigating HIV-risk sexual behaviors of men who have sex with men usually combines gay and bisexual men, treating them as a single, homogeneous group. However, gay and bisexual men may differ in their HIV risk behavior and in psychological characteristics indicative of risk. Exclusively gay (N = 1,180) and bisexual men (N = 136) completed anonymous surveys at gay bars. The surveys assessed demographic, psychological, and behavioral data related to sexual behavior and HIV risk. Relative to exclusively gay men, bisexual men had lower intentions to use condoms in their next intercourse occasion, reported a greater frequency of oral sex with men and more oral-sex partners, knew fewer people who were HIV positive, and perceived weaker peer norms favoring safer sex and risk avoidance. One-third of bisexual men reported engaging in unprotected anal intercourse, and 17% of bisexual men had multiple unprotected anal sex partners in the past two months. Interventions tailored to the needs of bisexual men are urgently needed and should focus on increasing intentions to use condoms, increasing HIV-risk sensitization, and fostering norms favoring safer sex and risk avoidance.

Adult↗
PubMedDate not supplied

Predictors of partner numbers in homosexual men: psychosocial factors in four societies.

Six hundred four homosexual men in four countries (Sweden, Finland, Australia, and the Republic of Ireland) were investigated with regard to their number of sexual partners over the past year and a number of psychological variables including masculinity and femininity, number of infections with sexually transmitted agents, relationships with parents, attitudes toward homosexuality, degree of homosexuality, sex-role conservatism, and a number of demographic variables. By use of multiple linear regression on partner numbers for each sample, it was found that between 15% and 28% of the variance of number of partners was accounted for by psychosocial factors, and that the great majority of these were significant in more than one country. Predictors included masculine and feminine personality traits, relationships with mother, degree of homosexuality, perceived societal attitudes toward homosexuality, age, and education. The data strongly suggest that psychosocial factors are significant predictors of numbers of partners of homosexual men, and that psychological approaches to treatment and prevention of sexually transmitted diseases may be warranted.

Adult↗