Subsets of proteins involved in distinct functional processes are subject to different selective pressures. We investigated whether there is an amino acid composition bias (AACB) inherent in discrete subsets of proteins, and whether we could identify changing patterns of AACB during the life cycle of the social bacterium Myxococcus xanthus. We quantitatively characterised the cellular, soluble secreted, and outer membrane vesicle (OMV) sub-proteomes of M. xanthus, identifying 315 proteins. The AACB of the cellular proteome differed only slightly from that deduced from the genome, suggesting that genome-inferred proteomes can accurately reflect the AACB of their host. Inferred AA deficiencies arising from prey consumption were exacerbated by the requirements of the 68%GC genome, whose character thus seems to be selected for directly rather than via the proteome. In our analysis, distinct subsets of the proteome (whether segregated spatially or temporally) exhibited distinct AACB, presumably tailored according to the needs of the organism's lifestyle and nutrient availability. Secreted AAs tend to be of lower cost than those retained in the cell, except for the early developmental A-signal, which is a particularly costly sub-proteome. We propose a model of AA reallocation during the M. xanthus life cycle, involving ribophagy during early starvation and sequestration of limiting AAs within cells during development.

Purpose The influence of vitamin D status on exercise-induced immune dysfunction remains unclear. The aim of this study was to investigate the effects of vitamin D status (circulating 25(OH)D) on innate immune responses and metabolomic profiles to prolonged exercise. Methods Twenty three healthy, recreationally active males (age 25 ± 7 years; maximal oxygen uptake [$${\dot{\text{V}}\text{O}}_{{2}}$$ V ˙ O 2 max] 56 ± 9 mL·kg−1·min−1), classified as being deficient (n = 7) or non-deficient n = 16) according to plasma concentrations of 25(OH)D, completed 2.5 h of cycling at 15% Δ (~ 55–60% $${\dot{\text{V}}\text{O}}_{{2}}$$ V ˙ O 2 max). Venous blood and unstimulated saliva samples were obtained before and after exercise. Results Participants with deficient plasma 25(OH)D on average had lower total lymphocyte count (mean difference [95% confidence interval], 0.5 cells × 109 L [0.1, 0.9]), p = 0.013) and greater neutrophil:lymphocyte ratio (1.3 cells × 109 L, [0.1, 2.5], p = 0.033). The deficient group experienced reductions from pre-exercise to 1 h post-exercise (− 43% [− 70, − 15], p = 0.003) in bacterial stimulated elastase in blood neutrophils compared to non-deficient participants (1% [− 20, 21], p = 1.000) Multivariate analyses of plasma metabolomic profiles showed a clear separation of participants according to vitamin D status. Prominent sources of variation between groups were purine/pyrimidine catabolites, inflammatory markers (linoleic acid pathway), lactate and tyrosine/adrenaline. Conclusion These findings provide evidence of the influence of vitamin D status on exercise-induced changes in parameters of innate immune defence and metabolomic signatures such as markers of inflammation and metabolic stress.

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As COVID-19 testing is rolled out increasingly widely, the use of a range of alternative testing methods will be beneficial in ensuring testing systems are resilient and adaptable to different clinical and public health scenarios. Here, we compare and discuss the diagnostic performance of a range of different molecular assays designed to detect the presence of SARS-CoV-2 infection in people with suspected COVID-19. Using findings from a systematic review of 103 studies, we categorised COVID-19 molecular assays into 12 different test classes, covering point-of-care tests, various alternative RT-PCR protocols, and alternative methods such as isothermal amplification. We carried out meta-analyses to estimate the diagnostic accuracy and clinical utility of each test class. We also estimated the positive and negative predictive values of all diagnostic test classes across a range of prevalence rates. Using previously validated RT-PCR assays as a reference standard, 11 out of 12 classes showed a summary sensitivity estimate of at least 92% and a specificity estimate of at least 99%. Several diagnostic test classes were estimated to have positive predictive values of 100% throughout the investigated prevalence spectrum, whilst estimated negative predictive values were more variable and sensitive to disease prevalence. We also report the results of clinical utility models that can be used to determine the information gained from a positive and negative test result in each class, and whether each test is more suitable for confirmation or exclusion of disease. Our analysis suggests that several tests exist that are suitable alternatives to standard RT-PCR and we discuss scenarios in which these could be most beneficial, such as where time to test result is critical or, where resources are constrained. However, we also highlight methodological concerns with the design and conduct of many included studies, and also the existence of likely publication bias for some test classes. Our results should be interpreted with these shortcomings in mind. Furthermore, our conclusions on test performance are limited to their use in symptomatic populations: we did not identify sufficient suitable data to allow analysis of testing in asymptomatic populations.