The effect of charge location in ion mobility mass spectrometry for small molecule analytes

In travelling wave IM-MS an electric field is applied across the IMS cell and analyte collisions with the inert gas give rise to a relationship between the drift time and the molecular shape and overall charge. Recent findings show near baseline IMS separation (R>1) where shape and overall charge appear not to explain the IMS separation. Multiple ion mobility peaks are observed for a single m/z including the fluoroquinolone antibiotics norfloxacin and lomefloxacin, the pesticide indoxacarb and a number of steroids

Can ion mobility mass spectrometry and density functional theory help elucidate protonation sites in 'small' molecules?

Ion mobility spectrometry-mass spectrometry (IMS-MS) offers an opportunity to combine measurements and/or calculations of the collision cross-sections and subsequent mass spectra with computational modelling in order to derive the three-dimensional structure of ions. IMS-MS has previously been reported to separate two components for the compound norfloxacin, explained by protonation on two different sites, enabling the separation of protonated isomers (protomers) using ion mobility with distinguishable tandem mass spectrometric (MS/MS) data. This study reveals further insights into the specific example of norfloxacin and wider implications for ion mobility mass spectrometry

Treatment of wild-type mice with 2,3-butanediol, a urinary biomarker of fmo5-/- mice, decreases plasma cholesterol and epididymal fat deposition

We previously showed that Fmo5−/− mice exhibit a lean phenotype and slower metabolic ageing. Their characteristics include lower plasma glucose and cholesterol, greater glucose tolerance and insulin sensitivity, and a reduction in age-related weight gain and whole-body fat deposition. In this paper, nuclear magnetic resonance (NMR) spectroscopy-based metabolite analyses of the urine of Fmo5−/− and wild-type mice identified two isomers of 2,3-butanediol as discriminating urinary biomarkers of Fmo5−/− mice. Antibiotic-treatment of Fmo5−/− mice increased plasma cholesterol concentration and substantially reduced urinary excretion of 2,3-butanediol isomers, indicating that the gut microbiome contributed to the lower plasma cholesterol of Fmo5−/− mice, and that 2,3-butanediol is microbially derived. Short- and long-term treatment of wild-type mice with a 2,3-butanediol isomer mix decreased plasma cholesterol and epididymal fat deposition but had no effect on plasma concentrations of glucose or insulin, or on body weight. In the case of long-term treatment, the effects were maintained after withdrawal of 2,3-butanediol. Short-, but not long-term treatment, also decreased plasma concentrations of triglycerides and non-esterified fatty acids. Fecal transplant from Fmo5−/− to wild-type mice had no effect on plasma cholesterol, and 2,3-butanediol was not detected in the urine of recipient mice, suggesting that the microbiota of the large intestine was not the source of 2,3-butanediol. However, 2,3-butanediol was detected in the stomach of Fmo5−/− mice, which was enriched for Lactobacillus genera, known to produce 2,3-butanediol. Our results indicate a microbial contribution to the phenotypic characteristic of Fmo5−/− mice of decreased plasma cholesterol and identify 2,3-butanediol as a potential agent for lowering plasma cholesterol

A multi-ingredient containing, proteins, carbohydrate and creatine does not attenuate humoral immune response or performance decrease compared to carbohydrate during resistance training

Background: Nowadays, only carbohydrate has shown to be an effective countermeasure to exercise-induced immune dysfunction while the effect of protein remains controversial. The purpose of this study was to investigate the acute effects of a commercially available multi-nutrient supplement on performance and salivary markers of humoral immunity, following a bout of circuit resistance training in young athletes. Methods: Twelve recreationally resistance-trained males (age: 22 ± 1.4 years; body mass 79 ±9.78 kg; 1.81 ± 0.07 m height) volunteered to participate in the study completing 2 randomised controlled circuit resistance training sessions (CT). Participants ingested 2 doses of 500ml of water mixed 60g of a multi-ingredient (MTN) containing whey proteins, carbohydrate, creatine, HMB and sodium bicarbonate or maltodextrin (PL). Beverages were consumed (3 doses of ~166ml) during and after the workout (1 × 500ml). Both MTN and PL looks the same colour and flavour and provide a similar amount of calories (~230 per serving). CT involved three rounds of 7 resistance exercises (CMJs, Bench Press, Parallel-Squat, Upright row, Alternate Lunges, Dead Lift, Push-press, Abdominals) followed by 1 min rest. Participants performed 12 repetitions at 70% 1RM in each of the exercises with no rest in between (only the time to change from one exercise to the next). Measurements included pre and post (30 min and 60 min) salivary markers of humoral immune response: Antimicrobial Peptide, Alpha Defensins (HNP 1-3). The total kg lifted per exercise and in the overall workout was considered as indicator of performance. ANOVA design and Cohen d effect sizes (ES) were used to analyse potential differences between times and treatment conditions. Results: No significant differences were observed between the total weight (kg) lifted per exercise or for the entire session (p > 0.05). HNP 1-3 showed a strong trend (p = 0.06) with a moderate effect size (d = 0.53) at 30 min for the CHO condition [2.001 (1.95) vs 3.037 (2.49) ng/mL], nevertheless, no significant differences were observed at 60 min with respect to the values measured at both pre [3.825 (3.21) vs 2.001 (1.95) ng/mL] and 30 min [3.825 (3.21) vs 3.037 (2.49) ng/mL]. On the other side, HNP 1-3 did not increase at either 30 min [2.464 (3.31) vs 3.656 (3.22) ng/mL] or 60 min [2.464(3.31) vs 2.387 (2.46) ng/mL] post workout for the MTN treatment condition. No differences were observed between the two tested treatment conditions for the three analysed times points (pre, post 30 min and post 60 min). Conclusion: Ingesting both MTN and CHO supplements during and after a circuit resistance-training workout, resulted in no impact on performance. However, even when both nutritional interventions were effective to attenuate the increase of antimicrobial peptide alpha-defensins, MTN showed a stronger effect to blunt exercise-induced immune-dysfunction. These results did not support the notion that only carbohydrate with no added proteins is the only effective nutritional countermeasure against the transient post exercise immunosuppression

Household Hardships, Public Programs, and Their Associations with the Health and Development of Very Young Children: Insights from Children’s HealthWatch

America’s low-income families struggle to protect their children from multiple threats to their health and growth. Many research and advocacy groups explore the health and educational effects of food insecurity, but less is known about these effects on very young children. Children’s HealthWatch, a group of pediatric clinicians and public health researchers, has continuously collected data on the effects of food insecurity alone and in conjunction with other household hardships since 1998. The group’s peer reviewed research has shown that a number of economic risks at the household level, including food, housing and energy insecurity, tend to be correlated. These insecurities alone or in conjunction increase the risk that a young child will suffer various negative health consequences, including increases in lifetime hospitalizations, parental report of fair or poor health,1 or risk for developmental delays.2 Child food insecurity is an incremental risk indicator above and beyond the risk imposed by household-level food insecurity. The Children’sHealthwatch research also suggests public benefits programs modify some of these effects for families experiencing hardships. This empirical evidence is presented in a variety of public venues outside the usual scientific settings, such as congressional hearings, to support the needs of America’s most vulnerable population through policy change. Children’s HealthWatch research supports legislative solutions to food insecurity, including sustained funding for public programs and re-evaluation of the use of the Thrifty Food Plan as the basis of SNAP benefits calculations. Children’s HealthWatch is one of many models to support the American Academy of Pediatrics’ call to “stand up, speak up, and step up for children.”3 No isolated group or single intervention will solve child poverty or multiple hardships. However, working collaboratively each group has a role to play in supporting the health and well-being of young children and their families. 1. Cook JT, Frank DA, Berkowitz C, et al. Food insecurity is associated with adverse health outcomes among human infants and toddlers. J Nutr. 2004;134:1432-1438. 2. Rose-Jacobs R, Black MM, Casey PH, et al. Household food insecurity: associations with at-risk infant and toddler development. Pediatrics. 2008;121:65-72. 3. AAP leader says to stand up, speak up, and step up for child health [news release]. Boston, MA: American Academy of Pediatrics; October 11, 2008. http://www2.aap.org/pressroom/nce/nce08childhealth.htm. Accessed January 1, 2012

2018 Alumni Achievement Awards Presentation

2018 Alumni Achievement Awards presentation

The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules

Recent studies have demonstrated that the CD3-ζ subunit of the T cell antigen receptor (TCR) complex is involved in signal transduction. However, the function of the remaining invariant subunits, CD3-γ, -δ, and , is still poorly understood. To examine their role in TCR function, we have constructed TCR/CD3 complexes devoid of functional ζ subunit and showed that they are still able to trigger the production of interleukin-2 in response to antigen or superantigen. These data, together with previous results, indicate that the TCR/CD3 complex is composed of at least two parallel transducing units, made of the γδ and ζ chains, respectively, Furthermore, the analysis of partially truncated ζ chains has led us to individualize a functional domain that may have constituted the building block of most of the transducing subunits associated with antigen receptors and some Fc receptors

CONQUEST Quality Standards : For the Collaboration on Quality Improvement Initiative for Achieving Excellence in Standards of COPD Care

Acknowledgments We thank Dr Seyi Soremekun, Jonathan Marshall, Jennie Medin and Irena Brookes-Smith for their valuable contributions to the design of the study. We would also like to acknowledge Ms Andrea Teh Xin Yi (BSc, Hons) of the Observational and Pragmatic Research Institute (OPRI), Singapore, for editorial and formatting assistance which supported the development of this publication. Professor Dave Singh is supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC). Funding CONQUEST is conducted by Optimum Patient Care Global and Observational and Pragmatic Research Institute and is co-funded by Optimum Patient Care Global and AstraZenecaPeer reviewedPublisher PD

Construction and physiochemical characterisation of a multi-composite, potential oral vaccine delivery system (VDS)

An increasing human population requires a secure food supply and a cost effective, oral vaccine delivery system for livestock would help facilitate this end. Recombinant antigen adsorbed onto silica beads and coated with myristic acid, was released (∼15% (w/v)) over 24 h at pH 8.8. At pH 2, the myristic acid acted as an enteric coating, protecting the antigen from a variety of proteases. The antigen adsorbed onto silica particles, coated in myristic acid had a conserved secondary structure (measured by circular dichroism (CD) spectroscopy) following its pH-triggered release. Small angle neutron scattering (SANS) was used to measure the thickness of the adsorbed antigen, finding that its adsorbed conformation was slightly greater than its solution radius of gyration, i.e. 120–160 Å. The addition of myristic acid led to a further increase in particle size, with scattering data consistent with an acid thickness slightly greater than a monolayer of fully extended alkyl chains and a degree of hydration of around 50%. Whilst adsorbed onto the silica and coated in myristic acid, the protein was stable over 14 days at 42 °C, indicating a reduced need for cold chain storage. These data indicate that further investigation is warranted into the development of this technology