Using HHsearch to tackle proteins of unknown function: A pilot study with PH domains.

Advances in membrane cell biology are hampered by the relatively high proportion of proteins with no known function. Such proteins are largely or entirely devoid of structurally significant domain annotations. Structural bioinformaticians have developed profile-profile tools such as HHsearch (online version called HHpred), which can detect remote homologies that are missed by tools used to annotate databases. Here we have applied HHsearch to study a single structural fold in a single model organism as proof of principle. In the entire clan of protein domains sharing the pleckstrin homology domain fold in yeast, systematic application of HHsearch accurately identified known PH-like domains. It also predicted 16 new domains in 13 yeast proteins many of which are implicated in intracellular traffic. One of these was Vps13p, where we confirmed the functional importance of the predicted PH-like domain. Even though such predictions require considerable work to be corroborated, they are useful first steps. HHsearch should be applied more widely, particularly across entire proteomes of model organisms, to significantly improve database annotations.

VAP, a Versatile Access Point for the Endoplasmic Reticulum: Review and analysis of FFAT-like motifs in the VAPome.

Dysfunction of VAMP-associated protein (VAP) is associated with neurodegeneration, both Amyotrophic Lateral Sclerosis and Parkinson's disease. Here we summarize what is known about the intracellular interactions of VAP in humans and model organisms. VAP is a simple, small and highly conserved protein on the cytoplasmic face of the endoplasmic reticulum (ER). It is the sole protein on that large organelle that acts as a receptor for cytoplasmic proteins. This may explain the extremely wide range of interacting partners of VAP, with components of many cellular pathways binding it to access the ER. Many proteins that bind VAP also target other intracellular membranes, so VAP is a component of multiple molecular bridges at membrane contact sites between the ER and other organelles. So far approximately 100 proteins have been identified in the VAP interactome (VAPome), of which a small minority have a "two phenylalanines in an acidic tract" (FFAT) motif as it was originally defined. We have analyzed the entire VAPome in humans and yeast using a simple algorithm that identifies many more FFAT-like motifs. We show that approximately 50% of the VAPome binds directly or indirectly via the VAP-FFAT interaction. We also review evidence on pathogenesis in genetic disorders of VAP, which appear to arise from reduced overall VAP levels, leading to ER stress. It is not possible to identify one single interaction that underlies disease. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.

Influence of exercise type on maternal blood pressure adaptation throughout pregnancy.

BACKGROUND: It has been reported that 10% of all pregnancies are complicated by a hypertensive disorder of pregnancy. Previous research has shown that moderate-vigorous intensity exercise has a positive effect on maternal resting blood pressure. A research gap, however, exists related to how different types of exercise (resistance, aerobic, combined resistance and aerobic) affect maternal blood pressure. Most of the previous studies solely focused on aerobic exercise. OBJECTIVE: The aim of this study was to examine the effects of exercise types on maternal blood pressure throughout pregnancy. STUDY DESIGN: This study employed a secondary analysis using data from a randomized controlled prenatal exercise intervention trial. This study utilized 3 exercise intervention groups (aerobic, resistance, combination) and compared the results with those of a nonexercize control group. Participants completed 3 50-minute sessions weekly from 16 weeks of gestation until delivery. Maternal vital signs and physical measurements such as systolic blood pressure, diastolic blood pressure, and heart rate were measured every 4 weeks throughout the intervention period. Between-group mean differences in maternal measurements were assessed using Pearson's chi-square tests for continuous (age, prepregnancy body mass index, heart rate, systolic blood pressure, diastolic blood pressure, pulse pressure) variables. For gravida, exact Wilcox 2-sample tests were performed to determine between-group differences in mean values. Hierarchical linear growth curves were used to estimate maternal trajectories of systolic blood pressure and diastolic blood pressure from 16 weeks to 36 weeks' gestation in each of the 4 groups (aerobic, combination, control, and resistance). RESULTS: There were no differences among the groups in maternal age or prepregnancy body mass index. Controlling for maternal body mass index, the lowest significant systolic blood pressure curve was noted throughout the pregnancy for women who participated in resistance exercise, followed by women in the aerobic exercise group all relative to the no exercise control group. At 36 weeks' gestation, the systolic blood pressure was lower in the resistance group by 12.17 mm Hg (P<.001) and in the aerobic group by 7.90 mm Hg (P<.001) relative to controls. No significant change in systolic blood pressure was noted in the combination group in comparison with controls at 36 weeks' gestation. Similarly, we demonstrated a significantly lower linear growth curve in diastolic blood pressure that was maintained throughout pregnancy in any exercise type relative to controls. After controlling for maternal body mass index, all 3 exercise types (combination, resistance, and aerobic) significantly predicted a similar decrease in diastolic blood pressure that was maintained throughout pregnancy. At 36 weeks' gestation, the diastolic blood pressure was lower in the aerobic group by 7.30 mm Hg (P<.01), in the combination group by 6.43 mm Hg (P<.05), and in the resistance group relative to controls. CONCLUSION: Overall, all exercise types were beneficial in lowering maternal resting blood pressure throughout pregnancy. Resistance training was noted to be the most beneficial in improving systolic blood pressure, followed by aerobic exercise. All 3 exercise groups were noted to improve diastolic blood pressure equally. Further research needs to be done to determine if either resistance or aerobic exercise throughout pregnancy decreases the risk for hypertensive disorders of pregnancy and the associated morbidity and mortality.

Drug Resistance and Novel Therapeutic Approaches in Invasive Candidiasis.

Candida species are the leading cause of invasive fungal infections worldwide and are associated with acute mortality rates of ~50%. Mortality rates are further augmented in the context of host immunosuppression and infection with drug-resistant Candida species. In this review, we outline antifungal drugs already in clinical use for invasive candidiasis and candidaemia, their targets and mechanisms of resistance in clinically relevant Candida species, encompassing not only classical resistance, but also heteroresistance and tolerance. We describe novel antifungal agents and targets in pre-clinical and clinical development, including their spectrum of activity, antifungal target, clinical trial data and potential in treatment of drug-resistant Candida. Lastly, we discuss the use of combination therapy between conventional and repurposed agents as a potential strategy to combat the threat of emerging resistance in Candida.

Marital, parental, and whole-family predictors of toddlers' emotion regulation: The role of parental emotional withdrawal.

The present study aims to address how dyadic and triadic family interactions across the transition to parenthood contribute to the later development of toddlers' adaptive emotion regulation using structural equation modeling methods. Specifically, we examined the interrelations of observed marital negative affect before childbirth, parents' emotional withdrawal during parent-infant interactions at 8 months, and coparenting conflict at 24 months as predictors of toddlers' adaptive emotion regulation at 24 months. Data for the present study were drawn from a longitudinal dataset in which 125 families were observed across the transition to parenthood. Results suggested that prenatal marital negativity predicted mothers' and fathers' emotional withdrawal toward their infants at 8 months postbirth as well as coparenting conflict at 24 months postbirth. Coparenting conflict and father-infant emotional withdrawal were negatively associated with toddlers' adaptive emotion regulation; however, mother-infant emotional withdrawal was not related. The implications of our study extend family systems research to demonstrate how multiple levels of detrimental family functioning over the first 2 years of parenthood influence toddlers' emotion regulation and highlight the importance of fathers' emotional involvement with their infants. (PsycINFO Database Record

Support for indoor tanning policies among young adult women who indoor tan.

The purpose of this study to examine support for indoor tanning policies and correlates of policy support among young adult women who indoor tan. Non-Hispanic white women ages 18-30 who indoor tanned in the past year (n = 356, M 23.3 age, SD 3.1) recruited in the Washington, DC area from 2013 to 2016 completed measures of indoor tanning behaviors, attitudes, perceptions, beliefs, and policy support. Most women in the sample supported policies to prevent children under the age of 18 from indoor tanning (74.0 %) and stronger warnings about the risks of indoor tanning on tanning devices (77.6 %); only 10.1 % supported a total ban. In multivariable analyses, support for individual indoor tanning policies varied by demographics (e.g., age), frequent indoor tanning behavior, indoor tanning beliefs, and risk perceptions. Non-Hispanic white young adult women who indoor tan, the primary consumers of indoor tanning, and a high-risk population, largely support indoor tanning prevention policies implemented by many state governments and those currently under review for national enactment. Given low levels of support for a total indoor tanning ban, support for other potential policies (e.g., increasing the minimum age to 21) should be investigated to inform future steps to reduce indoor tanning and the associated health risks.

Survey on Addressing the Information and Support Needs of Jewish Women at Increased Risk for or Diagnosed with Breast Cancer: The Sharsheret Experience.

Approximately 12% of women living in the United States will be diagnosed with breast cancer during their lifetimes. While all women face formidable challenges posed by the threat of living with or at increased risk for breast cancer, those of Ashkenazi Jewish descent face additional challenges owing to higher BRCA1/2 mutation prevalence in this population. Amidst calls for population-based screening for hereditary breast cancer risk, much can be learned from the experiences of Jewish women about their needs. The present study is a secondary analysis of psychoeducational program satisfaction and evaluation data previously collected by a community organization dedicated to serving women of all Jewish backgrounds facing, or at risk for, breast cancer. Among respondents (n = 347), over one-third were referred to the organization by family or friends, most often after a cancer crisis. Of the information and support resources offered, the greatest level of engagement occurred with the one-on-one peer support and health care symposia resources. Respondents endorsed high levels of satisfaction with the programs and services, and a strong desire to give back to the community. These data suggest that culturally-relevant information and support services for Jewish women could be scaled-up for larger dissemination to meet the anticipated needs in this special population.

A pilot study of research methods for determining the impact of pictorial cigarette warning labels among smokers.

BACKGROUND: Science to determine the impact of pictorial cigarette warning labels can inform decisions about warning label implementation and adjustments to their contents to maximize impact. This pilot study builds from earlier research on plain cigarette packaging to examine the feasibility of a method for determining the impact of pictorial warnings among smokers. FINDINGS: The study was a prospective, within-subjects pilot trial where smokers ages 18-30 (n = 10) were exposed to pictorial warnings on their cigarette packs. On day one, participants completed a baseline interview with an expired carbon monoxide reading and affixed pictorial warning labels to their cigarette pack(s) they would use the next day. On day two, participants completed mobile phone text message assessments of smoking behaviors and protocol adherence. On day three, participants completed a follow-up interview similar to baseline. We achieved 100% sample retention and adherence with procedures. Compared with baseline assessments of perceptions and behaviors related to existing text-only warnings, at follow-up participants were more likely to report that pictorial warnings used during the study were noticeable (M 4.1, SD 1.3 vs. M 2.7, SD 1.2, p = .013), stopped them from smoking (M 1.6, SD 0.8 vs. M 1.1, SD 0.3, p = .052), and conveyed health risks of smoking (M 3.5 SD 1.3 vs. M 2.2, SD 1.1, p = .006). At follow-up, participants also reported the protocol was acceptable. CONCLUSIONS: These findings suggest this is a feasible method that with further validation could provide evidence that can inform decisions regarding implementation of pictorial cigarette warnings.

Attitudes toward motherhood and social support as predictors of emotional distress in recently diagnosed young women with cancer undergoing fertility preservation / Actitudes hacia la maternidad y el apoyo social como predictores de trastornos emocionales en mujeres jóvenes con cáncer recientemente diagnosticadas que se someten a la preservación de la fertilidad

Objective. Young women with cancer can benefit from various treatment options for fertility preservation. More work is needed to discern which factors affect psychological outcomes and the decision to undergo fertility preservation for female cancer survivors. The purpose of this study was to examine the relationship between attitudes toward motherhood, concerns about fertility, satisfaction with information received, social support and emotional distress among young women with cancer undergoing fertility preservation treatment. Method. Cross-sectional administration of instruments (semi-structured interview, Scale of Perceived Social Support, BSI-18) to 115 young women (average age 31 years) newly diagnosed with cancer. Assessment was done on the same day or day after undergoing Ovarian Tissue Cryopreservation (OTC). Results. The degree of concern reported by the women when they knew that cancer treatment might affect their reproductive capacity was high. Almost half stated that they would change the treatment-related information they received. Factors influencing their decision to receive OTC include the importance of having a child and maintaining hormonal function. Higher emotional distress was significantly associated with increase desire to have children, belief that having children is necessary for couple's fulfillment, desire to change the information received, higher degree of concern about the possible loss of fertility, and less perceived social support. Conclusions. Both attitudes to motherhood and social support are factors that determine the emotional distress experienced by young women with cancer when faced with the possible loss of infertility. There is a need to offer fertility preservation counseling to these women

Objetivo. Mujeres jóvenes con cáncer pueden beneficiarse de opciones para la preservación de su fertilidad. Se necesitan estudios que determinen las implicaciones psicológicas de someterse a estas técnicas y de la propia decisión de recibirlas. Este estudio analiza el distres emocional, las preocupaciones sobre la fertilidad, las actitudes ante la maternidad, la satisfacción con la información recibida y el apoyo social en mujeres con cáncer que reciben un tratamiento de preservación de la fertilidad. Método. Una muestra de 115 mujeres (edad media 31 años) recién diagnosticas de cáncer fueron evaluadas (Entrevista semiestructurada, Escala de apoyo social percibido, BSI-18) el mismo día o día después de someterse a una criopreservación de tejido ovárico. Resultados. El grado de preocupación manifestado por las mujeres cuando supieron que el tratamiento del cáncer podría afectar su capacidad reproductiva fue alto. Casi la mitad declaró que cambiarían la información recibida sobre el tratamiento de preservación de la fertilidad. Un mayor distrés se asoció significativamente con mayor deseo de tener hijos, la creencia de que tener hijos es necesario para la relación de pareja, el deseo de cambiar la información recibida, mayor grado de preocupación por la posible pérdida de fertilidad y menor apoyo social. Conclusiones. Tanto las actitudes hacia la maternidad como el apoyo social son factores que determinan el distrés emocional que experimentan las mujeres jóvenes con cáncer cuando se enfrentan a la posible pérdida de infertilidad. Es necesario ofrecer asesoramiento sobre la preservación de la fertilidad a estas mujeres