Endogenous human cytomegalovirus gB is efficiently presented by MHC class II molecules to CD4+ CTL

Human cytomegalovirus (HCMV) infects endothelial, epithelial, and glial cells in vivo. These cells can express MHC class II proteins, but are unlikely to play important roles in priming host immunity. Instead, it seems that class II presentation of endogenous HCMV antigens in these cells allows recognition of virus infection. We characterized class II presentation of HCMV glycoprotein B (gB), a membrane protein that accumulates extensively in endosomes during virus assembly. Human CD4+ T cells specific for gB were both highly abundant in blood and cytolytic in vivo. gB-specific CD4+ T cell clones recognized gB that was expressed in glial, endothelial, and epithelial cells, but not exogenous gB that was fed to these cells. Glial cells efficiently presented extremely low levels of endogenous gB--expressed by adenovirus vectors or after HCMV infection--and stimulated CD4+ T cells better than DCs that were incubated with exogenous gB. Presentation of endogenous gB required sorting of gB to endosomal compartments and processing by acidic proteases. Although presentation of cellular proteins that traffic into endosomes is well known, our observations demonstrate for the first time that a viral protein sorted to endosomes is presented exceptionally well, and can promote CD4+ T cell recognition and killing of biologically important host cells

Video-supported Analysis of Beggiatoa Filament Growth, Breakage, and Movement

A marine Beggiatoa sp. was cultured in semi-solid agar with opposing oxygen-sulfide gradients. Growth pattern, breakage of filaments for multiplication, and movement directions of Beggiatoa filaments in the transparent agar were investigated by time-lapse video recording. The initial doubling time of cells was 15.7 ± 1.3 h (mean ± SD) at room temperature. Filaments grew up to an average length of 1.7 ± 0.2 mm, but filaments of up to approximately 6 mm were also present. First breakages of filaments occurred approximately 19 h after inoculation, and time-lapse movies illustrated that a parent filament could break into several daughter filaments within a few hours. In >20% of the cases, filament breakage occurred at the tip of a former loop. As filament breakage is accomplished by the presence of sacrificial cells, loop formation and the presence of sacrificial cells must coincide. We hypothesize that sacrificial cells enhance the chance of loop formation by interrupting the communication between two parts of one filament. With communication interrupted, these two parts of one filament can randomly move toward each other forming the tip of a loop at the sacrificial cell

Evolution of strigolactone receptors by gradual neofunctionalization of KAI2 paralogues

Background: Strigolactones (SLs) are a class of plant hormones that control many aspects of plant growth. The SL signalling mechanism is homologous to that of karrikins (KARs), smoke-derived compounds that stimulate seed germination. In angiosperms, the SL receptor is an a/p hydrolase known as DWARF14 (D14); its close homologue, KARRIKIN INSENSITIVE2 (KAI2), functions as a KAR receptor, and likely recognizes an uncharacterized, endogenous signal (‘KL’). Previous phylogenetic analyses have suggested that the KAI2 lineage is ancestral in land plants, and that canonical D14-type SL receptors only arose in seed plants; this is paradoxical, however, as nonvascular plants synthesize and respond to SLs. Results: We have used a combination of phylogenetic and structural approaches to re-assess the evolution of the D14/KAI2 family in land plants. We analyzed 339 members of the D14/KAI2 family from land plants and charophyte algae. Our phylogenetic analyses show that the divergence between the eu-KAI2 lineage and the DDK (D14/DLK2/KAI2) lineage that includes D14 occurred very early in land plant evolution. We show that eu-KAI2 proteins are highly conserved, and have unique features not found in DDK proteins. Conversely, we show that DDK proteins show considerable sequence and structural variation to each other, and lack clearly definable characteristics. We use homology modelling to show that the earliest members of the DDK lineage structurally resemble KAI2, and that SL receptors in non-seed plants likely do not have D14-like structure. We also show that certain groups of DDK proteins lack the otherwise conserved MAX2-interface, and may thus function independently of MAX2, which we show is highly conserved throughout land plant evolution. Conclusions: Our results suggest D14-like structure is not required for SL perception, and that SL perception has relatively relaxed structural requirements compared to KAI2-mediated signalling. We suggest that SL perception gradually evolved by neo-functionalization within the DDK lineage, and that the transition from KAI2-like to D14-like protein may have been driven by interactions with protein partners, rather than being required for SL perception per se

Pregnancy glycaemia and cord-blood levels of insulin and leptin in Pakistani and white British mother–offspring pairs: findings from a prospective pregnancy cohort

Aims/hypothesis To determine the extent to which gestational fasting and postload levels of glucose explain differences in infant fat mass between UK-born Pakistani and white British infants. Methods Analyses were undertaken in a prospective pregnancy cohort study of 1,415 women and their singleton live-born infants (629 white British and 786 Pakistani). Infant fat mass was assessed by cord-blood leptin levels and fetal insulin secretion by cord-blood insulin levels. Maternal OGTTs were completed at 26–28 weeks of gestation. Results Pakistani women had higher fasting and postload glucose levels and greater incidence of gestational diabetes than white British women. Higher fasting and postload glucose levels were associated with higher cord-blood levels of insulin and leptin in all participants, irrespective of ethnicity. Cord-blood leptin levels were 16% (95% CI 6, 26) higher in Pakistani than in white British infants. After adjustment for fasting glucose levels, this difference attenuated to 7% (−3, 16), and with additional adjustment for cord-blood insulin levels it attenuated further to 5% (−4, 14). Path analyses supported the hypothesis that fasting glucose levels mediate the relationship of Pakistani ethnicity to greater fat mass at birth, as measured by cord-blood leptin levels; on average, 19% of this mediation involved fetal insulin secretion. Postload glucose levels did not act as an important mediator of ethnic differences in cord-blood leptin levels. Results were very similar when 130 women with gestational diabetes were removed. Conclusions/interpretation These novel findings suggest a role of maternal pregnancy glycaemia in mediating differences in fat mass between Pakistani and white British infants

A model for removing the increased recall of recent events from the temporal distribution of autobiographical memory

The reminiscence bump is the tendency to recall relatively many personal events from the period in which the individual was between 10 and 30 years old. This effect has only been found in autobiographical memory studies that used participants who were older than 40 years of age. The increased recall of recent events possibly obscures the reminiscence bump in the results of younger participants. In this study, a model was proposed that removes the increase for recent events from the temporal distribution. The model basically estimates a retention function based on the 10 most recent years from the observed distributions and divides the observed distributions by predictions derived from the estimated retention function. The model was examined with three simulated data sets and one experimental data set. The results of the experiment offered two practical examples of how the model could be used to investigate the temporal distribution of autobiographical memories

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives

Bananas as an Energy Source during Exercise: A Metabolomics Approach

This study compared the acute effect of ingesting bananas (BAN) versus a 6% carbohydrate drink (CHO) on 75-km cycling performance and post-exercise inflammation, oxidative stress, and innate immune function using traditional and metabolomics-based profiling. Trained cyclists (N = 14) completed two 75-km cycling time trials (randomized, crossover) while ingesting BAN or CHO (0.2 g/kg carbohydrate every 15 min). Pre-, post-, and 1-h-post-exercise blood samples were analyzed for glucose, granulocyte (GR) and monocyte (MO) phagocytosis (PHAG) and oxidative burst activity, nine cytokines, F2-isoprostanes, ferric reducing ability of plasma (FRAP), and metabolic profiles using gas chromatography-mass spectrometry. Blood glucose levels and performance did not differ between BAN and CHO (2.41±0.22, 2.36±0.19 h, P = 0.258). F2-isoprostanes, FRAP, IL-10, IL-2, IL-6, IL-8, TNFα, GR-PHAG, and MO-PHAG increased with exercise, with no trial differences except for higher levels during BAN for IL-10, IL-8, and FRAP (interaction effects, P = 0.003, 0.004, and 0.012). Of 103 metabolites detected, 56 had exercise time effects, and only one (dopamine) had a pattern of change that differed between BAN and CHO. Plots from the PLS-DA model visualized a distinct separation in global metabolic scores between time points [R2Y(cum) = 0.869, Q2(cum) = 0.766]. Of the top 15 metabolites, five were related to liver glutathione production, eight to carbohydrate, lipid, and amino acid metabolism, and two were tricarboxylic acid cycle intermediates. BAN and CHO ingestion during 75-km cycling resulted in similar performance, blood glucose, inflammation, oxidative stress, and innate immune levels. Aside from higher dopamine in BAN, shifts in metabolites following BAN and CHO 75-km cycling time trials indicated a similar pattern of heightened production of glutathione and utilization of fuel substrates in several pathways

Murine model for Fusarium oxysporum invasive fusariosis reveals organ-specific structures for dissemination and long-term persistence

Peer reviewedPublisher PD

Traffic-Related Air Pollution and Perinatal Mortality: A Case–Control Study

BACKGROUND: Ambient levels of air pollution may affect the health of children, as indicated by studies of infant and perinatal mortality. Scientific evidence has also correlated low birth weight and preterm birth, which are important determinants of perinatal death, with air pollution. However, most of these studies used ambient concentrations measured at monitoring sites, which may not consider differential exposure to pollutants found at elevated concentrations near heavy-traffic roadways. OBJECTIVES: Our goal was to examine the association between traffic-related pollution and perinatal mortality. METHODS: We used the information collected for a case-control study conducted in 14 districts in the City of Sao Paulo, Brazil, regarding risk factors for perinatal deaths. We geocoded the residential addresses of cases (fetal and early neonatal deaths) and controls (children who survived the 28th day of life) and calculated a distance-weighted traffic density (DWTD) measure considering all roads contained in a buffer surrounding these homes. RESULTS: Logistic regression revealed a gradient of increasing risk of early neonatal death with higher exposure to traffic-related air pollution. Mothers exposed to the highest quartile of the DWTD compared with those less exposed exhibited approximately 50% increased risk (adjusted odds ratio = 1.47; 95% confidence interval, 0.67-3.19). Associations for fetal mortality were less consistent. CONCLUSIONS: These results suggest that motor vehicle exhaust exposures may be a risk factor for perinatal mortality

Bovine colostrum supplementation and upper respiratory symptoms during exercise training: a systematic review and meta-analysis of randomised controlled trials

Abstract Background Bovine colostrum is proposed as a nutritional countermeasure to the risk of upper respiratory symptoms (URS) during exercise training. The aim of this systematic review and meta-analysis was to estimate the size of the effect of bovine colostrum supplementation on URS. Methods Databases (CDSR, CENTRAL, Cinahl, ClinicalTrials.gov, Current Controlled Trials, DARE, EMBASE, Medline, PROSPERO and Web of Science) of published, unpublished and ongoing studies were searched for randomised controlled trials of healthy adults (≥18 years), evaluating the effect of oral bovine colostrum supplementation compared to a concurrent control group on URS. Results Five trials (152 participants) met the inclusion criteria, all of which involved individuals involved in regular exercise training. Over an 8–12 week follow-up period, bovine colostrum supplementation when compared to placebo significantly reduced the incidence rate of URS days (rate ratio 0.56, 95 % confidence intervals 0.43 to 0.72, P value < 0.001) and URS episodes (0.62, 0.40 to 0.99, P value = 0.04) by 44 and 38 % respectively. There were limited data and considerable variation in results of included studies for duration of URS episodes hence a meta-analysis of this outcome was deemed inappropriate. The risk of bias assessment in this review was hindered by poor reporting practices of included studies. Due to incomplete reporting of study methods, four of the five studies were judged to have a moderate or high risk of overall bias. Our findings must be interpreted in relation to quantity and quality of the available evidence. Conclusions The present systematic review and meta-analysis provides evidence that bovine colostrum supplementation may be effective in preventing the incidence of URS days and episodes in adults engaged in exercise training. The fact that the majority of included studies did not report significant effects on URS outcomes mitigates concerns about publication bias. The point estimates of the random-effects meta-analyses are greater than the smallest clinically important difference, but the low precision of the individual study estimates means the evidence presented in this review needs to be followed up with an appropriately designed and adequately powered, randomised control trial