33 research outputs found

    Targeted nasal vaccination provides antibody-independent protection against Staphylococcus aureus.

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    Despite showing promise in preclinical models, anti-Staphylococcus aureus vaccines have failed in clinical trials. To date, approaches have focused on neutralizing/opsonizing antibodies; however, vaccines exclusively inducing cellular immunity have not been studied to formally test whether a cellular-only response can protect against infection. We demonstrate that nasal vaccination with targeted nanoparticles loaded with Staphylococcus aureus antigen protects against acute systemic S. aureus infection in the absence of any antigen-specific antibodies. These findings can help inform future developments in staphylococcal vaccine development and studies into the requirements for protective immunity against S. aureus

    Measurement of the νe and total 8B solar neutrino fluxes with the Sudbury Neutrino Observatory phase-III data set

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    This paper details the solar neutrino analysis of the 385.17-day phase-III data set acquired by the Sudbury Neutrino Observatory (SNO). An array of 3He proportional counters was installed in the heavy-water target to measure precisely the rate of neutrino-deuteron neutral-current interactions. This technique to determine the total active 8B solar neutrino flux was largely independent of the methods employed in previous phases. The total flux of active neutrinos was measured to be 5.54-0.31+0.33(stat.)-0.34+0.36(syst.)×106 cm-2 s-1, consistent with previous measurements and standard solar models. A global analysis of solar and reactor neutrino mixing parameters yielded the best-fit values of Δm2=7.59-0.21+0.19×10 -5eV2 and θ=34.4-1.2+1.3degrees

    Scintillator ageing of the T2K near detectors from 2010 to 2021

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    The T2K experiment widely uses plastic scintillator as a target for neutrino interactions and an active medium for the measurement of charged particles produced in neutrino interactions at its near detector complex. Over 10 years of operation the measured light yield recorded by the scintillator based subsystems has been observed to degrade by 0.9–2.2% per year. Extrapolation of the degradation rate through to 2040 indicates the recorded light yield should remain above the lower threshold used by the current reconstruction algorithms for all subsystems. This will allow the near detectors to continue contributing to important physics measurements during the T2K-II and Hyper-Kamiokande eras. Additionally, work to disentangle the degradation of the plastic scintillator and wavelength shifting fibres shows that the reduction in light yield can be attributed to the ageing of the plastic scintillator. The long component of the attenuation length of the wavelength shifting fibres was observed to degrade by 1.3–5.4% per year, while the short component of the attenuation length did not show any conclusive degradation

    Associations between dietary patterns, eating behaviours, and body composition and adiposity in 3-year children of mothers with obesity

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    BACKGROUND: The relationships between eating habits, behaviours, and the development of obesity in preschool children is not well established. OBJECTIVE: As children of mothers with obesity are themselves at risk of obesity, we examined these relationships in a cohort of 482 three-year-old children of mothers with obesity from the UK Pregnancy Better Eating and Activity Trial (UPBEAT). METHOD: Dietary patterns were derived using factor analysis of an 85-item food frequency questionnaire (FFQ). Eating behaviours were assessed using the Children's Eating Behaviour Questionnaire (CEBQ). Measures of body composition included age-specific BMI cut-offs, WHO z scores, sum of skinfolds, waist and arm circumferences, and body fat percentage. Using adjusted regression analysis, we examined associations between dietary patterns, eating behaviours, and measures of body composition. RESULTS: Three distinct dietary patterns were defined: "healthy/prudent," "African/Caribbean," and "processed/snacking." The "processed/snacking" pattern was associated with greater odds of obesity; OR 1.53 (95% CI, 1.07-2.19). The "African/Caribbean" and the "healthy/prudent" patterns were associated with a lower arm circumference (β = -0.23 cm [-0.45 to -0.01]) and sum of skinfolds (β = -1.36 cm [-2.88 to -0.37]), respectively. Lower enjoyment of food and food responsiveness, and greater slowness in eating and satiety, were associated with lower arm and waist circumferences, WHO z scores, and obesity (all P < .05). CONCLUSION: In children of mothers with obesity, those who had higher scores on a "processed/snacking" dietary pattern had greater odds of obesity. In contrast, slowness in eating was associated with lower measures of body composition. These novel findings highlight modifiable behaviours in high-risk preschool children which could contribute to public health strategies for prevention of childhood obesity

    Transmembrane Peptides Influence the Affinity of Sterols for Phospholipid Bilayers

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    Cholesterol is distributed unevenly between different cellular membrane compartments, and the cholesterol content increases from the inner bilayers toward the plasma membrane. It has been suggested that this cholesterol gradient is important in the sorting of transmembrane proteins. Cholesterol has also been to shown play an important role in lateral organization of eukaryotic cell membranes. In this study the aim was to determine how transmembrane proteins influence the lateral distribution of cholesterol in phospholipid bilayers. Insight into this can be obtained by studying how cholesterol interacts with bilayer membranes of different composition in the presence of designed peptides that mimic the transmembrane helices of proteins. For this purpose we developed an assay in which the partitioning of the fluorescent cholesterol analog CTL between LUVs and mβCD can be measured. Comparison of how cholesterol and CTL partitioning between mβCD and phospholipid bilayers with different composition suggests that CTL sensed changes in bilayer composition similarly as cholesterol. Therefore, the results obtained with CTL can be used to understand cholesterol distribution in lipid bilayers. The effect of WALP23 on CTL partitioning between DMPC bilayers and mβCD was measured. From the results it was clear that WALP23 increased both the order in the bilayers (as seen from CTL and DPH anisotropy) and the affinity of the sterol for the bilayer in a concentration dependent way. Although WALP23 also increased the order in DLPC and POPC bilayers the effects on CTL partitioning was much smaller with these lipids. This indicates that proteins have the largest effect on sterol interactions with phospholipids that have longer and saturated acyl chains. KALP23 did not significantly affect the acyl chain order in the phospholipid bilayers, and inclusion of KALP23 into DMPC bilayers slightly decreased CTL partitioning into the bilayer. This shows that transmembrane proteins can both decrease and increase the affinity of sterols for the lipid bilayers surrounding proteins. This is likely to affect the sterol distribution within the bilayer and thereby the lateral organization in biomembranes
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