The relationship between potentially traumatic or stressful events, HIV infection and neurocognitive impairment (NCI): a systematic review of observational epidemiological studies.

BACKGROUND: HIV/AIDS and potentially traumatic events (PTEs) or stressful life events (SLEs) and/or PTSD are independently associated with neurocognitive impairment (NCI). Literature suggests that HIV and PTE/SLE exposure independently and consistently affect various domains of cognition including language ability, working memory and psychomotor speed. There are limited data on the interaction between HIV infection and PTEs and their combined effect on NCI. OBJECTIVE: In this systematic review, we synthesise evidence for the combined effect of HIV infection and PTEs and SLEs and/or post-traumatic stress disorder (PTSD) on NCI of people living with HIV/AIDS (PLWHA) from high-, middle- and low- income countries. METHOD: Our inclusion criteria were observational epidemiological studies (case-control, cohort and cross-sectional designs) that investigated the interaction of HIV infection, PTEs and SLEs and/or PTSD and specifically their combined effect on NCI in adults. We searched a number of electronic databases including Pubmed/Medline, PsycINFO, Scopus and Global Health using the search terms: cognition, HIV/AIDS, observational studies, trauma and permutations thereof. RESULTS: Fifteen studies were included in the review, of which the majority were conducted in high-income countries. Ten of the fifteen studies were conducted in the United States of America (USA) and five in South Africa. Seven of these focused on early life stress/childhood trauma. The remaining studies assessed adult-onset PTEs and SLEs only. Eight studies included women only. Overall, the studies suggest that PTE and SLE exposure and/or PTSD are a significant risk factor for NCI in adults living with HIV, with impairments in memory and executive functions being the most likely consequence of PTE and SLE exposure. CONCLUSION: These findings highlight the need for trauma screening and for the integration of trauma-focused interventions in HIV care to improve outcomes.

Antecedentes: El VIH/SIDA y los eventos potencialmente traumáticos (PTEs) o los eventos estresantes de la vida (SLEs) y/o TEPT se asocian independientemente con el deterioro neurocognitivo (NCI). La literatura sugiere que la exposición al VIH, PTE y SLE afecta de manera independiente y consistente varios dominios de la cognición, incluida la capacidad del lenguaje, la memoria de trabajo y la velocidad psicomotora. Hay datos limitados sobre la interacción entre la infección por VIH y los PTE, y su efecto combinado sobre el NCI.Objetivo: En esta revisión sistemática sintetizamos evidencia del efecto combinado de la infección por VIH, PTEs y SLEs, y/o TEPT en el NCI de personas que viven con VIH/SIDA (PLWHA) en países de ingresos altos, medios y bajos.Método: Nuestros criterios de inclusión fueron estudios epidemiológicos observacionales (diseño de caso-control, cohortes y diseños transversales) que investigaron la interacción de la infección por VIH, PTEs y SLEs y/o TEPT, y específicamente su efecto combinado sobre el NCI en adultos. Se realizaron búsquedas en varias bases de datos electrónicas, que incluyeron a Pubmed/Medline, PsycINFO, Scopus y Global Health, utilizando los términos de búsqueda: cognición, VIH/SIDA, estudios de observación, trauma y permutaciones de los mismos.Resultados: Quince estudios se incluyeron en la revisión, de los cuales la mayoría se realizaron en países de altos ingresos. Diez de los quince estudios fueron realizados en los Estados Unidos de América (EE.UU.) y cinco en Sudáfrica. Siete de éstos se centraron en el estrés de la vida temprana/trauma infantil. Los estudios restantes evaluaron PTEs y SLEs cuya aparición fue en la vida adulta solamente. Ocho estudios incluyeron sólo mujeres. En general, los estudios sugieren que la exposición a PTE y SLE y/o TEPT es un factor de riesgo significativo para NCI en adultos que viven con VIH, con el deterioro en la memoria y las funciones ejecutivas como la consecuencia más probable de la exposición a PTE y SLE.Conclusión: Estos hallazgos resaltan la necesidad de la detección de traumas y la integración de intervenciones centradas en el trauma en la atención del VIH para mejorar sus resultados.

The relationship between cognitive change and physical health and behavioural outcomes in a Ugandan cohort of adults living with HIV - a longitudinal study.

We investigated changes in cognitive function and physical health and behavioural outcomes (HIV disease progression, health-seeking behaviour, adherence to HIV medications and risky sexual behaviour) at baseline and 12 months later among 1126 Ugandan adults living with HIV. Overall, cognitive function improved from baseline to follow-up, except for gait speed, which was slower at follow-up compared to baseline. There were improvements in physical health and behavioural outcomes by follow-up, with greater improvements among individuals on ART compared to those not on ART. Change in gait speed over time significantly predicted risky sexual behaviours at follow-up. This is the first study to investigate the longitudinal relationships between cognitive function and health outcomes among Ugandan adults living with HIV and provide insights into the possible links between cognitive function and negative clinical and behavioural health outcomes in people living with HIV.

Can digital breast tomosynthesis perform better than standard digital mammography work-up in breast cancer assessment clinic?

PURPOSE: To compare the efficacy of use of digital breast tomosynthesis (DBT) with standard digital mammography (DM) workup views in the breast cancer assessment clinic. MATERIALS AND METHODS: The Tomosynthesis Assessment Clinic trial (TACT), conducted between 16 October 2014 and 19 April 2016, is an ethics-approved, monocenter, multireader, multicase split-plot reading study. After written informed consent was obtained, 144 females (age > 40 years) who were recalled to the assessment clinic were recruited into TACT. These cases (48 cancers) were randomly allocated for blinded review of (1) DM workup and (2) DBT, both in conjunction with previous DM from the screening examination. Fifteen radiologists of varying experience levels in the Australia BreastScreen Program were included in this study, wherein each radiologist read 48 cases (16 cancers) in 3 non-overlapping blocks. Diagnostic accuracy was measured by means of sensitivity, specificity, and positive (PPV) and negative predictive values (NPV). The receiver-operating characteristic area under the curve (AUC) was calculated to determine radiologists' performances. RESULTS: Use of DBT (AUC = 0.927) led to improved performance of the radiologists (z = 2.62, p = 0.008) compared with mammography workup (AUC = 0.872). Similarly, the sensitivity, specificity, PPV, and NPV of DBT (0.93, 0.75, 0.64, 0.96) were higher than those of the workup (0.90, 0.56, 0.49, 0.92). Most radiologists (80%) performed better with DBT than standard workup. Cancerous lesions on DBT appeared more severe (U = 33,172, p = 0.02) and conspicuous (U = 24,207, p = 0.02). There was a significant reduction in the need for additional views (χ2 = 17.63, p < 0.001) and recommendations for ultrasound (χ2 = 8.56, p = 0.003) with DBT. CONCLUSIONS: DBT has the potential to increase diagnostic accuracy and simplify the assessment process in the breast cancer assessment clinic. KEY POINTS: • Use of DBT in the assessment clinic results in increased diagnostic accuracy. • Use of DBT in the assessment clinic improves performance of radiologists and also increases the confidence in their decisions. • DBT may reduce the need for additional views, ultrasound imaging, and biopsy.

'Restoring the person's life': a qualitative study to inform development of care for people with severe mental disorders in rural Ethiopia.

AIMS: In low-income countries, care for people with severe mental disorders (SMDs) who manage to access treatment is usually emergency-based, intermittent or narrowly biomedical. The aim of this study was to inform development of a scalable district-level mental health care plan to meet the long-term care needs of people with SMD in rural Ethiopia. METHODS: The present study was carried out as formative work for the Programme for Improving Mental health CarE which seeks to develop, implement and evaluate a district level model of integrating mental health care into primary care. Six focus group discussions and 25 in-depth interviews were conducted with service planners, primary care providers, traditional and religious healers, mental health service users, caregivers and community representatives. Framework analysis was used, with findings mapped onto the domains of the Innovative Care for Chronic Conditions (ICCC) framework. RESULTS: Three main themes were identified. (1) Focused on 'Restoring the person's life', including the need for interventions to address basic needs for food, shelter and livelihoods, as well as spiritual recovery and reintegration into society. All respondents considered this to be important, but service users gave particular emphasis to this aspect of care. (2) Engaging with families, addressed the essential role of families, their need for practical and emotional support, and the importance of equipping families to provide a therapeutic environment. (3) Delivering collaborative, long-term care, focused on enhancing accessibility to biomedical mental health care, utilising community-based health workers and volunteers as an untapped resource to support adherence and engagement with services, learning from experience of service models for chronic communicable diseases (HIV and tuberculosis) and integrating the role of traditional and religious healers alongside biomedical care. Biomedical approaches were more strongly endorsed by health workers, with traditional healers, religious leaders and service users more inclined to see medication as but one component of care. The salience of poverty to service planning was cross-cutting. CONCLUSIONS: Stakeholders prioritised interventions to meet basic needs for survival and endorsed a multi-faceted approach to promoting recovery from SMD, including social recovery. However, sole reliance on this over-stretched community to mobilise the necessary resources may not be feasible. An adapted form of the ICCC framework appeared highly applicable to planning an acceptable, feasible and sustainable model of care.

Cryogenic Tensile Strength and Fatigue Life of Carbon Nanotube Multi-Yarn.

Carbon nanotube (CNT) multi-yarns, consisting of 30 yarns, were tested under monotonic tensile load and fatigue at the room temperature (298 K) and two cryogenic temperatures (232 and 123 K). Tensile stiffness increased with the decrease of temperature. The average ultimate tensile strength was higher at 123 K when compared to the higher temperatures (232 and 298 K). Failure mechanism changed from a combination of classical variant and independent fiber breakage at the two higher temperatures to mostly classical variant failure mechanism at the lower temperature. The CNT-yarn's fatigue life also increased with decreasing temperature. CNT-yarns have been shown to function well at lower temperatures making them usable for applications requiring operation at cryogenic temperatures, such as in satellites and high altitude aircraft.

High-Temperature Cross-Linking of Carbon Nanotube Multi-Yarn Using Polyvinylpyrrolidone as a Binding Agent.

Carbon nanotube (CNT) multi-yarn was cross-linked together at elevated temperatures using a poly- mer, with the intent of improving their strength and electrical conductivity. They were functionalized using an acid treatment and immersed in a bath of different concentrations (0.5%, 0.1%, and 0.2%) of polyvinylpyrrolidone (PVP). Then they were placed in an oven at various temperatures (180 °C, 200 °C, and 220 °C) in order to cause cross-linking among the carbon nanotube yarns. The phys- ical, chemical, electrical, and mechanical properties of the cross-linked yarns were investigated. The yarns cross-linked at higher temperatures and greater concentrations of PVP had a greater increase in linear mass density, indicating that the cross-linking process had worked as expected. Yarns that were cross-linked at lower temperatures had greater tensile strength and better spe- cific electrical conductivity. Those that were treated with a greater concentration of polymer had a greater ultimate tensile strength. All these results are encouraging first step, but still need further development if CNT yarn is to replace copper wire.

Surveillance and Outbreak Response Management System (SORMAS) to support the control of the Ebola virus disease outbreak in West Africa.

In the context of controlling the current outbreak of Ebola virus disease (EVD), the World Health Organization claimed that 'critical determinant of epidemic size appears to be the speed of implementation of rigorous control measures', i.e. immediate follow-up of contact persons during 21 days after exposure, isolation and treatment of cases, decontamination, and safe burials. We developed the Surveillance and Outbreak Response Management System (SORMAS) to improve efficiency and timeliness of these measures. We used the Design Thinking methodology to systematically analyse experiences from field workers and the Ebola Emergency Operations Centre (EOC) after successful control of the EVD outbreak in Nigeria. We developed a process model with seven personas representing the procedures of EVD outbreak control. The SORMAS system architecture combines latest In-Memory Database (IMDB) technology via SAP HANA (in-memory, relational database management system), enabling interactive data analyses, and established SAP cloud tools, such as SAP Afaria (a mobile device management software). The user interface consists of specific front-ends for smartphones and tablet devices, which are independent from physical configurations. SORMAS allows real-time, bidirectional information exchange between field workers and the EOC, ensures supervision of contact follow-up, automated status reports, and GPS tracking. SORMAS may become a platform for outbreak management and improved routine surveillance of any infectious disease. Furthermore, the SORMAS process model may serve as framework for EVD outbreak modeling.

Web-based questionnaires to capture acute infections in long-term cohorts : findings of a feasibility study.

BACKGROUND: Incidence of acute respiratory infections (ARI) and gastrointestinal infections (GII) are difficult to assess due to high frequency episodes, limited severity and short duration. Retrospective assessments therefore are particularly prone to recall bias, while prospective assessment with conventional questionnaires requires high discipline from participants which is difficult to maintain over longer time periods. Web-based questionnaires (WQ) allow integration of a recall system and thus carry the potential to prospectively capture acute infections. We investigated the feasibility of a weekly WQ assessing symptoms of ARI and GII among participants of the German National Cohort (GNC). MATERIAL AND METHODS: In the study centres Hamburg and Bremen of the GNC participants of the Pretest 1 phase (September to November 2011) were invited to additionally take part in this feasibility study testing the WQ. Every Monday participants received an e-mail, containing a link to the WQ, asking for occurrence of ARI or GII symptoms during the past 7 days. The study took place from the beginning of February until mid-July 2012. We calculated the overall proportion of participation, weekly participation and the number of weekly reports per participant and we estimated incidences of ARI, ILI and GII. RESULTS: Of 200 Pretest 1 participants 171 (86 %) reported having an email address and thus were eligible for the web-based study. A total of 167 (98 %) agreed to participate. Participants of the web-based study were younger and better educated than non-participants. Access to Internet decreased with increasing age. Of the 167 participants in the feasibility study, 144 (86 %) responded at least once during the study period of 23 weeks, 5 persons (3 %) had non-functioning email addresses and 18 (11 %) did not respond at all. The weekly response varied between 62 % and 81 %, the median was 74 % (IQR: 71-77 %). Weekly median reports per person were 20 (IQR: 14-22; range 1-23). More than 90 % of participants responded during the first 3 days. The following mean incidence rates were found: ARI, 12 %; ILI, 0.49 %; and GII, 3 %. CONCLUSION: Use of WQ in prospective studies seems well possible, as Internet access is frequent among study participants and major technical problems did not occur. We observed high participation during the study period of 6 months and low drop out numbers. Participants of the web-based study were slightly younger and better educated than non-participants, so selection bias is possible and must be kept in mind when discussing generalizability of the results.

Therapeutic targeting of naturally presented myeloperoxidase-derived HLA peptide ligands on myeloid leukemia cells by TCR-transgenic T cells.

T cells have been proven to be therapeutically effective in patients with relapsed leukemias, although target antigens on leukemic cells as well as T-cell receptors (TCRs), potentially recognizing those antigens, are mostly unknown. We have applied an immunopeptidomic approach and isolated human leukocyte antigen (HLA) ligands from primary leukemia cells. We identified a number of ligands derived from different genes that are restrictedly expressed in the hematopoietic system. We exemplarily selected myeloperoxidase (MPO) as a potential target and isolated a high-avidity TCR with specificity for a HLA-B*07:02-(HLA-B7)-restricted epitope of MPO in the single HLA-mismatched setting. T cells transgenic for this TCR demonstrated high peptide and antigen specificity as well as leukemia reactivity in vitro and in vivo. In contrast, no significant on- and off-target toxicity could be observed. In conclusion, we here demonstrate, exemplarily for MPO, that leukemia-derived HLA ligands can be selected for specific effector tool development to redirect T cells to be used for graft manipulation or adoptive T-cell therapies in diverse transplant settings. This approach can be extended to other HLA ligands and HLA molecules in order to provide better treatment options for this life-threatening disease.

Creep and inverse stress relaxation behaviors of carbon nanotube yarns.

Creep, creep recovery and inverse stress relaxation behaviors of carbon nanotube yarns that consisted of 1-, 30-, and 100-yarn(s) were characterized. Primary and secondary creep stages were observed over the duration of 336 h. The primary creep stage lasted for about 4 h at an applied load equal to 75% of the ultimate tensile strength. The total strain in the primary stage was significantly larger in the carbon nanotube multi-yarn than in the carbon nanotube 1-yarn. In the secondary stage, 1-yarn also had a smaller steady state strain rate than the multi-yarn, and it was independent of number of yarns in multi-yarn. Strain response under cyclic creep loading condition was comparable to its counterpart in non-cyclic (i.e., standard) creep test except that strain response during the first cycle was slightly different from the subsequent cycles. Inverse creep (i.e., strain recovery) was observed in the 100-yarn during the cyclic creep tests after the first unloading cycle. Furthermore, inverse stress relaxation of the multi-yarns was characterized. Inverse stress relaxation was larger and for longer duration with the larger number of yarns.

Using a treatment partner and text messaging to improve adherence to psychotropic medication: a qualitative formative study of service users and caregivers in Cape Town, South Africa.

OBJECTIVE: Poor adherence to medications, including psychotropic medications contributes to the burden of disease. Mental health service users (MHSU) may also not attend follow-up appointments at their health care facilities where they could discuss adherence with their health care provider. This paper reports on preliminary qualitative research preceding a randomised controlled trial that aims to improve adherence to psychotropic medication and to follow up treatment visits. The intervention will entail the support of individuals with serious mental disorder by a treatment partner and short message service (SMS) text messaging. METHODS: The preliminary research reported in this paper aimed to extract views about the intervention from both mental health service users (MHSU) and caregivers through focus group discussions and individual interviews. Data were analysed using ATLAS TI qualitative software. RESULTS: The caregivers interviewed were all mothers of MHSU who took measures to encourage adherence. They held mixed opinions on whether the treatment partner should be a family member. Most participants expressed the view that due to living conditions, family members were natural treatment partners, but others stated that they would prefer a treatment partner who was not a family member. Similarly, while most MHSU supported the idea of a treatment partner, a minority were concerned that a treatment partner may potentially be too controlling and compromise their autonomy. The vast majority of participants supported SMS text messaging as a means of reminding MHSU to take their medication and attend follow-up appointments. One participant mentioned the importance of broader social inclusion issues that should be incorporated in the intervention. CONCLUSION: Qualitative research may provide useful insights for the design of interventions of this nature related to social inclusion randomised control trials with its focus on adherence.

Applicability and fairness of the oral examination in undergraduate psychiatry training in South Africa.

OBJECTIVE: There are several methods of evaluating medical students' performance, such as written examination, oral examination and objective structured clinical examination (OSCE). Many studies have focused on the reliability and validity of these methods but few studies have explored comparison between these methods. Psychiatry is the only subject at the University of Stellenbosch where the final assessment consists of solely an oral component. The aim of the study was to compare students' final overall and discipline specific examination marks (i.e. in the other subjects) with the examination marks in psychiatry, and to determine if content or structure (e,g. oral, written or OSCE format) of examination impacts more on the student performance in the examination. METHOD: 343 final year medical students were included. All undertook their psychiatry rotation at the University of Stellenbosch, South Africa during 2008 and 2009. Data of marks obtained in all the disciplines during 2008 and 2009 were collected and class marks were compared with their final examination marks across all disciplines. Bland-Altman plots were used to assess the level of agreement between the class and examination marks. Cases below the lower threshold were compared to all other cases across all disciplines. The odds ratio for group status was calculated for gender distribution of examiners. RESULTS: The psychiatry class mark and final oral examination mark provided similar measures within a width of 31.5. Cases below the threshold had poorer performance in two other disciplines. The gender distribution of the examiners (female-female) significantly increased the odds ratio for poorer performance in the oral examination. CONCLUSION: The results suggest that a group of students underperform in their final examination independent of method of evaluation and that the gender of examiners impacts on examination marks. Therefore future research should focus on identifying and modifying factors (including choice of examiner combinations) that contribute to the poor performance of medical students in their final examination, in order to help students perform better. Gender distribution of examiners should also be considered when examinations are structured and designed.

Family therapy for schizophrenia: cultural challenges and implementation barriers in the South African context.

Family therapy is an effective, evidence based intervention for schizophrenia. This literature review explores the impact of culture on family therapy as a treatment model for schizophrenia and examines how cultural beliefs impact on access to care. Although there is a good deal of evidence to suggest that certain principles of family therapy such as empathy and psycho-education are universal, there is a paucity of literature about the role of culture in designing family interventions for people living with schizophrenia in a culturally diverse setting such as South Africa. It is well acknowledged that cultural ideologies influence families' belief systems of schizophrenia, expected expressed emotion, and levels of stigma in relation to mental illness. Additionally, in adapting models designed for first-world settings, consideration needs to be given to aspects such as language, educational level and accessibility of mental health care facilities. Family therapists are increasingly recognising the need for the study and implementation of evidence based culture-relevant and culture-responsive therapeutic techniques. These techniques need to be cost-effective and will require training, supervision, staff support, and management input in order to become generally available.

The structure of endothiapepsin complexed with the gem-diol inhibitor PD-135,040 at 1.37 A.

The crystal structure of endothiapepsin complexed with the gem-diol inhibitor PD-135,040 has been anisotropically refined to a resolution of 1.37 A. The structure of this inhibitor complex is in agreement with previous structures of endothiapepsin gem-diol inhibitor complexes that have been used to develop proposed catalytic mechanisms. However, the increase in resolution over previous structures confirms the presence of a number of short hydrogen bonds within the active site that are likely to play an important role in the catalytic mechanism. The presence of low-barrier hydrogen bonds was indicated in a previous one-dimensional H NMR spectrum.

Self-association of model transmembrane alpha-helices is modulated by lipid structure.

We have developed a fluorescence quenching method using peptides containing 3,5-dibromotryrosine to measure oligomerization of model transmembrane alpha-helices in lipid bilayers. Peptides of the type Ac-LysLysGlyLeu(m)XLeu(n)LysLysAla-amide where X is tryptophan or 3,5-dibromotyrosine were found to form heterodimers in bilayers of phosphatidylcholine in the liquid-crystalline phase. The free energy of dimer formation changed little with increasing number of Leu residues from 16 to 22 but increased with increasing phospholipid fatty acyl chain length, with a slope of about 0.5 kJ mol(-1) per fatty acyl chain carbon. Peptides were excluded from lipid in the gel phase, resulting in increased levels of oligomerization. Addition of cholesterol to form the liquid-ordered state led to increased dimerization but without phase separation. The presence of phosphatidylethanolamine had little effect on dimerization.

Fabrication and characterization of microwell array chemical sensors.

Microwell arrays have been fabricated on the distal face of coherent fiber-optic bundles. A typical microwell array comprises approximately 3,000 individual optical fibers that were etched chemically. Individual microwells were 1 to 14-microm deep with approximately 22-microm widths and were filled partially with a chemical sensing (polymer + dye) layer to produce a microwell array sensor (MWAS). MWASs were fabricated using a technically expedient, photoinitiated polymerization reaction whereby a approximately 2 to 10-microm thick pH-sensitive or O2-sensitive sensing layer was immobilized inside each microwell. The pH-sensing layer comprised fluorescein isothiocyanate-dextran conjugate immobilized in a photopolymerizable poly(vinyl alcohol) membrane. The O2-sensing layer comprised a ruthenium metal complex entrapped in a gas-permeable photopolymerizable siloxane membrane. pH and PO2 were quantitated by acquiring luminescence images using an epifluorescence microscope/charge-coupled device imaging system. The pH-sensitive MWAS displayed a pKa of approximately 6.4 and a response time of approximately 2.5 s. The O2-sensitive MWAS behaved according to a nonlinear Stern-Volmer model with a maximum I0/I of approximately 4 and a response time of approximately 2.5 s. MWASs are advantageous in that suitably sized samples such as single biological cells can be co-localized with the sensing matrix in individual microwells.

Effects of aromatic residues at the ends of transmembrane alpha-helices on helix interactions with lipid bilayers.

We have studied the effects of aromatic residues at the ends of peptides of the type Ac-KKGL(n)()WL(m)()KKA-amide on their interactions with lipid bilayers as a function of lipid fatty acyl chain length, physical phase, and charge. Peptide Ac-KKGFL(6)WL(8)FKKA-amide (F(2)L(14)) incorporated into bilayers of phosphatidylcholines containing monounsaturated fatty acyl chains of lengths C14-C24 at a peptide:lipid molar ratio of 1:100 in contrast to Ac-KKGL(7)WL(9)KKA-amide (L(16)) which did not incorporate at all into dierucoylphosphatidylcholine [di(C24:1)PC]; Ac-KKGYL(6)WL(8)YKKA-amide (Y(2)L(14)) incorporated partly into di(C24:1)PC. Lipid-binding constants relative to that for dioleoylphosphatidylcholine (C18:1)PC were obtained using a fluorescence quenching method. For Y(2)L(14) and F(2)L(14), relative lipid-binding constants increased with increasing fatty acyl chain length from C14 to C24; strongest binding did not occur at the point where the hydrophobic length of the peptide equalled the hydrophobic thickness of the bilayer. For Ac-KKGYL(9)WL(11)YKKA-amide (Y(2)L(20)), increasing chain length from C18 to C24 had little effect on relative binding constants. Anionic phospholipids bound more strongly than zwitterionic phospholipids to Y(2)L(14) and Y(2)L(20) but effects of charge were relatively small. In two phase (gel and liquid crystalline) mixtures, all the peptides partitioned more strongly into liquid crystalline than gel phase; effects were independent of the structure of the peptide or of the lipid (dipalmitoylphosphatidylcholine or bovine brain sphingomyelin). Addition of cholesterol had little effect on incorporation of the peptides into lipid bilayers. It is concluded that the presence of aromatic residues at the ends of transmembrane alpha-helices effectively buffers them against changes in bilayer thickness caused either by an increase in the chain length of the phospholipid or by the presence of cholesterol.

Anionic phospholipids decrease the rate of slippage on the Ca(2+)-ATPase of sarcoplasmic reticulum.

Accumulation of Ca(2+) by the Ca(2+)-ATPase of skeletal-muscle sarcoplasmic reticulum has been measured in reconstituted, sealed vesicles as a function of lipid composition. Measurements were performed in the presence of carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) to eliminate any effects of H(+) transport; in the presence of FCCP, addition of valinomycin had no effect on the level or rate of accumulation of Ca(2+) showing that, in the presence of FCCP, no electrical potential built up across the membrane. Levels of accumulation were low when the phospholipid was dioleoylphosphatidylcholine (DOPC), even though DOPC supports high ATPase activity. Inclusion of 10 mol% anionic phospholipid [dioleoylphosphatidic acid (DOPA) or dioleoylphosphatidylserine (DOPS)] led to higher levels of accumulation of Ca(2+), 10 mol% being the optimum concentration. Cardiolipin or phosphatidylinositol 4-phosphate were more effective than DOPA or DOPS in increasing accumulation of Ca(2+). Effects of anionic phospholipids were seen in the presence of an ATP-regenerating system to remove ADP, and in the presence of phosphate within the reconstituted vesicles to precipitate calcium phosphate. Rates of passive leak of Ca(2+) from the reconstituted vesicles were slow. The Ca(2+)-accumulation process was simulated assuming either simple passive leak of Ca(2+) from the vesicles or assuming slippage on the ATPase, a process in which the phosphorylated intermediate of the ATPase releases bound Ca(2+) on the cytoplasmic rather than the lumenal side of the membrane. The experimental data fitted to a slippage model, with anionic phospholipids decreasing the rate of slippage.