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Identification of diverse lipid-binding modes in the groove of zinc α2 glycoprotein reveals its functional versatilityZAG is a multifunctional glycoprotein with a class I MHC-like protein fold and an α1-α2 lipid-binding groove. The intrinsic ZAG ligand is unknown. Our previous studies showed that ZAG binds the dansylated C11 fatty acid, DAUDA, differently to the boron dipyrromethane C16 fatty acid, C16-BODIPY. Here, the molecular basis for this difference was elucidated. Multi-wavelength analytical ultracentrifugation confirmed that DAUDA and C16-BODIPY individually bind to ZAG and compete for the same binding site. Molecular docking of lipid-binding in the structurally related CD1-proteins predicted nine conserved ligand contact residues in ZAG. Twelve mutants were accordingly created by alanine scanning site directed mutagenesis for characterisation. Mutation of Y12 caused ZAG to misfold. Mutation of K147, R157 and A158 abrogated C16-BODIPY but not DAUDA binding. L69 and T169 increased the fluorescence emission intensity of C16-BODIPY but not of DAUDA compared to wild-type ZAG and showed that C16-BODIPY binds close to T169 and L69. Distance measurements of the crystal structure revealed K147 forms a salt bridge with D83. A range of bioactive bulky lipids including phospholipids and sphingolipids displaced DAUDA from the ZAG binding site but unexpectedly did not displace C16-BODIPY. We conclude that the ZAG α1-α2 groove contains separate but overlapping sites for DAUDA and C16-BODIPY and is involved in binding to a bulkier and wider repertoire of lipids than previously reported. This work suggested that the in vivo activity of ZAG may be dictated by its lipid ligand.
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Enabling women to access preferred methods of contraception: a rapid review and behavioural analysisMany pregnancies in the UK are either unplanned or ambivalent. This review aimed to (i) explore barriers and facilitators to women choosing and accessing a preferred method of contraception in the United Kingdom, and (ii) identify opportunities for behavioural interventions based on examination of interventions that are currently available nationally. Three databases were searched, and experts contacted to identify grey literature for studies presenting barriers and facilitators to women choosing and accessing a preferred method of contraception, conducted in the UK and published between 2009 and October 2019. Information on barriers and facilitators were coded into overarching themes, which were then coded into Mechanisms of Actions (MoAs) as listed in the Theory and Techniques Tool. National interventions were identified by consulting stakeholders and coded into the Behaviour Change Wheel. The match between barriers/facilitators and intervention content was assessed using the Behaviour Change Wheel. We included 32 studies and identified 46 barrier and facilitator themes. The most cited MoA was Environmental Context and Resources, which primarily related to the services women had access to and care they received. Social Influences, Beliefs about Consequences (e.g., side effects) and Knowledge were also key. The behavioural analysis highlighted four priority intervention functions (Modelling, Enablement, Education and Environmental Restructuring) that can be targeted to support women to choose and access their preferred method of contraception. Relevant policy categories and behaviour change techniques are also highlighted. This review highlights factors that influence women's choices and access to contraception and recommends opportunities that may be targeted for future interventions in order to support women to access preferred contraception. Protocol was registered with PROSPERO (an international database of prospectively registered systematic reviews in health and social care) in December 2019, CRD42019161156 .
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Breakfast consumption suppresses appetite but does not increase daily energy intake or physical Activity energy expenditure when compared with breakfast omission in adolescent girls who habitually skip breakfast: a 7-day randomised crossover trialWith concerns that adolescent girls often skip breakfast, this study compared the effects of breakfast consumption versus breakfast omission on free-living physical activity (PA) energy expenditure (PAEE) and dietary intakes among adolescent girls classified as habitual breakfast skippers. The participants went through two 7-day conditions in a trial with a crossover design: daily standardised breakfast consumption (energy content: 25% of resting metabolic rate) before 09:00 (BC) and daily breakfast omission (no energy-providing nutrients consumed) until 10:30 (BO). Free-living PAEE, dietary intakes, and perceived appetite, tiredness, and energy levels were assessed. Analyses were linear mixed models. Breakfast manipulation did not affect PAEE or PA duration. Daily fibre intake was higher (p = 0.005; d = 1.31), daily protein intake tended to be higher (p = 0.092; d = 0.54), post-10:30 carbohydrate intake tended to be lower (p = 0.096; d = 0.41), and pre-10:30 hunger and fullness were lower and higher, respectively (p ≤ 0.065; d = 0.33–1.01), in BC versus BO. No other between-condition differences were found. Breakfast-skipping adolescent girls do not compensate for an imbalance in energy intake caused by breakfast consumption versus omission through subsequent changes in PAEE but may increase their carbohydrate intakes later in the day to partially compensate for breakfast omission. Furthermore, breakfast can make substantial contributions to daily fibre intake among adolescent girls.
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The effects of extended planning time on candidates’ performance, processes and strategy use in the lecture listening-into-speaking tasks of the TOEFL iBT TestThis study investigated the effects of two different planning time conditions (i.e., operational [20 s] and extended length [90 s]) for the lecture listening-into-speaking tasks of the TOEFL iBT® test for candidates at different proficiency levels. Seventy international students based in universities and language schools in the United Kingdom (35 at a lower level; 35 at a higher level) participated in the study. The effects of different lengths of planning time were examined in terms of (a) the scores given by ETS-certified raters; (b) the quality of the speaking performances characterized by accurately reproduced idea units and the measures of complexity, accuracy, and fluency; and (c) self-reported use of cognitive and metacognitive processes and strategies during listening, planning, and speaking. The results found neither a statistically significant main effect of the length of planning time nor an interaction between planning time and proficiency on the scores or on the quality of the speaking performance. There were several cognitive and metacognitive processes and strategies where significantly more engagement was reported under the extended planning time, which suggests enhanced cognitive validity of the task. However, the increased engagement in planning did not lead to any measurable improvement in the score. Therefore, in the interest of practicality, the results of this study provide justifications for the operational length of planning time for the lecture listening-into-speaking tasks in the speaking section of the TOEFL iBT test.
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Prevalence of Human Immunodeficiency Virus among pregnant women in NigeriaBackground Human Immunodeficiency Virus (HIV) infection among pregnant women has been associated with a number of adverse maternal and infant outcomes. Nigeria accounts for about 10% of the HIV/AIDS burden worldwide and has the second highest incidence of new HIV infections among women globally. This study estimated the overall prevalence of HIV among pregnant women in Nigeria and examined variations across the geo-political zones of the country. Methods We conducted a systematic review and meta-analysis. A comprehensive search was conducted using eight electronic databases and grey sources for studies published from 1·1·2008 to 31·8·2019. Primary studies reporting prevalence estimates of HIV among pregnant women diagnosed using a diagnostic/ screening test were identified, screened and appraised using a two-stage process. A meta-analysis was conducted with the primary outcome measure as proportion (%) of pregnant women identified as having HIV infection. Results Twenty three eligible studies involving 72,728 pregnant women were included in the meta-analysis. The overall pooled prevalence of HIV among pregnant women was 7·22% (95% CI: 5·64, 9·21). A high degree of heterogeneity (I2=97·2%) and publication bias (p = 0.728) was reported. Prevalence rate for South-East geo-political zone (17·04%, 95% CI: 9·01, 29·86) was higher compared to the overall prevalence. Conclusions Findings imply that 7 out of every 100 pregnant women in Nigeria are likely to have HIV infection. The magnitude of the issue highlight the need for targeted efforts at local, national and international levels towards prevention, diagnosis and treatment.
