Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis

BACKGROUND. Tuberculosis (TB) kills more people than any other infection, and new diagnostic tests to identify active cases are required. We aimed to discover and verify novel markers for TB in nondepleted plasma. / METHODS. We applied an optimized quantitative proteomics discovery methodology based on multidimensional and orthogonal liquid chromatographic separation combined with high-resolution mass spectrometry to study nondepleted plasma of 11 patients with active TB compared with 10 healthy controls. Prioritized candidates were verified in independent UK (n = 118) and South African cohorts (n = 203). / RESULTS. We generated the most comprehensive TB plasma proteome to date, profiling 5022 proteins spanning 11 orders-of-magnitude concentration range with diverse biochemical and molecular properties. We analyzed the predominantly low–molecular weight subproteome, identifying 46 proteins with significantly increased and 90 with decreased abundance (peptide FDR ≤ 1%, q ≤ 0.05). Verification was performed for novel candidate biomarkers (CFHR5, ILF2) in 2 independent cohorts. Receiver operating characteristics analyses using a 5-protein panel (CFHR5, LRG1, CRP, LBP, and SAA1) exhibited discriminatory power in distinguishing TB from other respiratory diseases (AUC = 0.81). / CONCLUSION. We report the most comprehensive TB plasma proteome to date, identifying novel markers with verification in 2 independent cohorts, leading to a 5-protein biosignature with potential to improve TB diagnosis. With further development, these biomarkers have potential as a diagnostic triage test. / FUNDING. Colciencias, Medical Research Council, Innovate UK, NIHR, Academy of Medical Sciences, Program for Advanced Research Capacities for AIDS, Wellcome Centre for Infectious Diseases Research

Longitudinal study of the associations between change in sedentary behavior and change in adiposity during childhood and adolescence:Gateshead Millennium Study

BACKGROUND: Sedentary time (ST) has been reported to have a range of negative health effects in adults, however, the evidence for such effects among children and adolescents is sparse. The primary aim of the study was to examine associations between changes in sedentary behavior (time and fragmentation) and changes in adiposity across childhood and adolescence. METHODS: Participants were recruited as part of the Gateshead Millennium Study. Measures were taken at age 7y (n=502), 9y (n=506), 12y (n=420) and 15y (n=306). Participants wore an ActiGraph GT1M and accelerometer epochs were 'sedentary' when recorded counts were ⩽25 counts/15 s. ST was calculated and fragmentation (SF) was assessed by calculating the number of sedentary bouts per sedentary hour. Associations of changes in ST and SF with changes in adiposity (Body Mass Index (BMI), and Fat Mass Index (FMI)) were examined using bivariate linear spline models. RESULTS: Increasing ST by 1% per year was associated with an increase in BMI of 0.08 kg/m(2)/year (95%CI: 0.06-0.10; P<0.001) and FMI of 0.15 kg/m(2)/year (0.11-0.19; P<0.001). Change in SF was associated with BMI and FMI (P<0.001). An increase of 1 bout per sedentary hour per year (i.e. sedentary time becoming more fragmented) was associated with an increase in BMI of 0.07 kg/m(2)/year (0.06-0.09; P<0.001) and an increase in FMI of 0.14 kg/m(2)/year (0.10-0.18; P<0.001) over the 8y period. However, an increase in SF between 9y-12y was associated with a 0.09 kg/m(2)/year decrease in BMI (-0.18-0.00; p=0.046) and 0.11 kg/m(2)/year decrease in FMI (-0.22-0.00; P=0.049). CONCLUSIONS: Increased ST and increased SF from 7y to 15y were associated with increased adiposity. This is the first study to show age-specific associations between change in objectively measured sedentary behaviour and adiposity after adjustment of MVPA in children and adolescents.. The study suggests that, targeting sedentary behaviour for obesity prevention may be most effective during periods in which we see large increases in ST.International Journal of Obesity accepted article preview online, 15 March 2017. doi:10.1038/ijo.2017.69

Roadmap on dynamics of molecules and clusters in the gas phase

This roadmap article highlights recent advances, challenges and future prospects in studies of the dynamics of molecules and clusters in the gas phase. It comprises nineteen contributions by scientists with leading expertise in complementary experimental and theoretical techniques to probe the dynamics on timescales spanning twenty order of magnitudes, from attoseconds to minutes and beyond, and for systems ranging in complexity from the smallest (diatomic) molecules to clusters and nanoparticles. Combining some of these techniques opens up new avenues to unravel hitherto unexplored reaction pathways and mechanisms, and to establish their significance in, e.g. radiotherapy and radiation damage on the nanoscale, astrophysics, astrochemistry and atmospheric science