Daily life stress and the cortisol awakening response : testing the anticipation hypothesis

Acknowledgments We thank Paul Stewart for his contribution to data collection and Dr Matthew Jones for programming the handheld computers. Author Contributions Conceived and designed the experiments: WS DJP. Performed the experiments: DJP. Analyzed the data: WS. Wrote the paper: WS DJP.Peer reviewedPublisher PD

Fluctuating selection models and Mcdonald-Kreitman type analyses

It is likely that the strength of selection acting upon a mutation varies through time due to changes in the environment. However, most population genetic theory assumes that the strength of selection remains constant. Here we investigate the consequences of fluctuating selection pressures on the quantification of adaptive evolution using McDonald-Kreitman (MK) style approaches. In agreement with previous work, we show that fluctuating selection can generate evidence of adaptive evolution even when the expected strength of selection on a mutation is zero. However, we also find that the mutations, which contribute to both polymorphism and divergence tend, on average, to be positively selected during their lifetime, under fluctuating selection models. This is because mutations that fluctuate, by chance, to positive selected values, tend to reach higher frequencies in the population than those that fluctuate towards negative values. Hence the evidence of positive adaptive evolution detected under a fluctuating selection model by MK type approaches is genuine since fixed mutations tend to be advantageous on average during their lifetime. Never-the-less we show that methods tend to underestimate the rate of adaptive evolution when selection fluctuates

From weak coupling to spinning strings

We identify the gauge theory dual of a spinning string of minimal energy with spins S_1, S_2 on AdS_5 and charge J on S^5. For this purpose we focus on a certain set of local operators with two different types of covariant derivatives acting on complex scalar fields. We analyse the corresponding nested Bethe equations for the ground states in the limit of large spins. The auxiliary Bethe roots form certain string configurations in the complex plane, which enable us to derive integral equations for the leading and sub-leading contribution to the anomalous dimension. The results can be expressed through the observables of the sl(2) sub-sector, i.e. the cusp anomaly f(g) and the virtual scaling function B_L(g), rendering the strong-coupling analysis straightforward. Furthermore, we also study a particular sub-class of these operators specialising to a scaling limit with finite values of the second spin at weak and strong coupling.Comment: 23 pages, 3 figures, minor changes, references adde

Measurement of cortisol in saliva: a comparison of measurement error within and between international academic-research laboratories

Objective: Hundreds of scientific publications are produced annually that involve the measurement of cortisol in saliva. Intra- and inter-laboratory variation in salivary cortisol results has the potential to contribute to cross- study inconsistencies in findings, and the perception that salivary cortisol results are unreliable. This study rigor- ously estimates sources of measurement variability in the assay of salivary cortisol within and between established international academic-based laboratories that specialize in saliva analyses. One hundred young adults (Mean age: 23.10 years; 62 females) donated 2 mL of whole saliva by passive drool. Each sample was split into multiple- 100 µL aliquots and immediately frozen. One aliquot of each of the 100 participants’ saliva was transported to academic laboratories (N = 9) in the United States, Canada, UK, and Germany and assayed for cortisol by the same commercially available immunoassay. Results: 1.76% of the variance in salivary cortisol levels was attributable to differences between duplicate assays of the same sample within laboratories, 7.93% of the variance was associated with differences between laboratories, and 90.31% to differences between samples. In established-qualified laboratories, measurement error of salivary cortisol is minimal, and inter-laboratory differences in measurement are unlikely to have a major influence on the determined values

Exclusive neuronal expression of SUCLA2 in the human brain

SUCLA2 encodes the ATP-forming subunit (A-SUCL-) of succinyl-CoA ligase, an enzyme of the citric acid cycle. Mutations in SUCLA2 lead to a mitochondrial disorder manifesting as encephalomyopathy with dystonia, deafness and lesions in the basal ganglia. Despite the distinct brain pathology associated with SUCLA2 mutations, the precise localization of SUCLA2 protein has never been investigated. Here we show that immunoreactivity of A-SUCL- in surgical human cortical tissue samples was present exclusively in neurons, identified by their morphology and visualized by double labeling with a fluorescent Nissl dye. A-SUCL- immunoreactivity co-localized >99% with that of the d subunit of the mitochondrial F0-F1 ATP synthase. Specificity of the anti-A-SUCL- antiserum was verified by the absence of labeling in fibroblasts from a patient with a complete deletion of SUCLA2. A-SUCL- immunoreactivity was absent in glial cells, identified by antibodies directed against the glial markers GFAP and S100. Furthermore, in situ hybridization histochemistry demonstrated that SUCLA2 mRNA was present in Nissl-labeled neurons but not glial cells labeled with S100. Immunoreactivity of the GTP-forming subunit (G-SUCL-) encoded by SUCLG2, or in situ hybridization histochemistry for SUCLG2 mRNA could not be demonstrated in either neurons or astrocytes. Western blotting of post mortem brain samples revealed minor G-SUCL- immunoreactivity that was however, not upregulated in samples obtained from diabetic versus non-diabetic patients, as has been described for murine brain. Our work establishes that SUCLA2 is expressed exclusively in neurons in the human cerebral cortex

Definition of the σW regulon of Bacillus subtilis in the absence of stress

Bacteria employ extracytoplasmic function (ECF) sigma factors for their responses to environmental stresses. Despite intensive research, the molecular dissection of ECF sigma factor regulons has remained a major challenge due to overlaps in the ECF sigma factor-regulated genes and the stimuli that activate the different ECF sigma factors. Here we have employed tiling arrays to single out the ECF σW regulon of the Gram-positive bacterium Bacillus subtilis from the overlapping ECF σX, σY, and σM regulons. For this purpose, we profiled the transcriptome of a B. subtilis sigW mutant under non-stress conditions to select candidate genes that are strictly σW-regulated. Under these conditions, σW exhibits a basal level of activity. Subsequently, we verified the σW-dependency of candidate genes by comparing their transcript profiles to transcriptome data obtained with the parental B. subtilis strain 168 grown under 104 different conditions, including relevant stress conditions, such as salt shock. In addition, we investigated the transcriptomes of rasP or prsW mutant strains that lack the proteases involved in the degradation of the σW anti-sigma factor RsiW and subsequent activation of the σW-regulon. Taken together, our studies identify 89 genes as being strictly σW-regulated, including several genes for non-coding RNAs. The effects of rasP or prsW mutations on the expression of σW-dependent genes were relatively mild, which implies that σW-dependent transcription under non-stress conditions is not strictly related to RasP and PrsW. Lastly, we show that the pleiotropic phenotype of rasP mutant cells, which have defects in competence development, protein secretion and membrane protein production, is not mirrored in the transcript profile of these cells. This implies that RasP is not only important for transcriptional regulation via σW, but that this membrane protease also exerts other important post-transcriptional regulatory functions

The science of clinical practice: disease diagnosis or patient prognosis? Evidence about "what is likely to happen" should shape clinical practice.

BACKGROUND: Diagnosis is the traditional basis for decision-making in clinical practice. Evidence is often lacking about future benefits and harms of these decisions for patients diagnosed with and without disease. We propose that a model of clinical practice focused on patient prognosis and predicting the likelihood of future outcomes may be more useful. DISCUSSION: Disease diagnosis can provide crucial information for clinical decisions that influence outcome in serious acute illness. However, the central role of diagnosis in clinical practice is challenged by evidence that it does not always benefit patients and that factors other than disease are important in determining patient outcome. The concept of disease as a dichotomous 'yes' or 'no' is challenged by the frequent use of diagnostic indicators with continuous distributions, such as blood sugar, which are better understood as contributing information about the probability of a patient's future outcome. Moreover, many illnesses, such as chronic fatigue, cannot usefully be labelled from a disease-diagnosis perspective. In such cases, a prognostic model provides an alternative framework for clinical practice that extends beyond disease and diagnosis and incorporates a wide range of information to predict future patient outcomes and to guide decisions to improve them. Such information embraces non-disease factors and genetic and other biomarkers which influence outcome. SUMMARY: Patient prognosis can provide the framework for modern clinical practice to integrate information from the expanding biological, social, and clinical database for more effective and efficient care

Combination of electroweak and QCD corrections to single W production at the Fermilab Tevatron and the CERN LHC

Precision studies of the production of a high-transverse momentum lepton in association with missing energy at hadron colliders require that electroweak and QCD higher-order contributions are simultaneously taken into account in theoretical predictions and data analysis. Here we present a detailed phenomenological study of the impact of electroweak and strong contributions, as well as of their combination, to all the observables relevant for the various facets of the p\smartpap \to {\rm lepton} + X physics programme at hadron colliders, including luminosity monitoring and Parton Distribution Functions constraint, $W$ precision physics and search for new physics signals. We provide a theoretical recipe to carefully combine electroweak and strong corrections, that are mandatory in view of the challenging experimental accuracy already reached at the Fermilab Tevatron and aimed at the CERN LHC, and discuss the uncertainty inherent the combination. We conclude that the theoretical accuracy of our calculation can be conservatively estimated to be about 2% for standard event selections at the Tevatron and the LHC, and about 5% in the very high $W$ transverse mass/lepton transverse momentum tails. We also provide arguments for a more aggressive error estimate (about 1% and 3%, respectively) and conclude that in order to attain a one per cent accuracy: 1) exact mixed ${\cal O}(\alpha \alpha_s)$ corrections should be computed in addition to the already available NNLO QCD contributions and two-loop electroweak Sudakov logarithms; 2) QCD and electroweak corrections should be coherently included into a single event generator.Comment: One reference added. Final version to appear in JHE

Measurement of inclusive J/ψ suppression in Au+Au collisions at sNN=200 GeV through the dimuon channel at STAR

J/ψ suppression has long been considered a sensitive signature of the formation of the Quark-Gluon Plasma (QGP) in relativistic heavy-ion collisions. In this letter, we present the first measurement of inclusive J/ψ production at mid-rapidity through the dimuon decay channel in Au+Au collisions at sNN=200 GeV with the STAR experiment. These measurements became possible after the installation of the Muon Telescope Detector was completed in 2014. The J/ψ yields are measured in a wide transverse momentum (pT) range of 0.15 GeV/c to 12 GeV/c from central to peripheral collisions. They extend the kinematic reach of previous measurements at RHIC with improved precision. In the 0-10% most central collisions, the J/ψ yield is suppressed by a factor of approximately 3 for pT>5 GeV/c relative to that in p+p collisions scaled by the number of binary nucleon-nucleon collisions. The J/ψ nuclear modification factor displays little dependence on pT in all centrality bins. Model calculations can qualitatively describe the data, providing further evidence for the color-screening effect experienced by J/ψ mesons in the QGP