Tetracyclines are among the most used antibiotics in livestock worldwide. Resistance is widely disseminated in Escherichia coli, where it is generally mediated by tetracycline efflux pumps, such as ...TetA. Expression of tetracycline efflux pumps is tightly controlled by the repressor TetR, which has been shown to be tetracycline-responsive at sub-MIC tetracycline concentrations. The objective of this study was to investigate the effects of increasing tetracycline concentrations on the growth of TetA-producing E. coli, and to determine how expression of tetA and tetR related to each other in different growth phases in the presence of tetracycline.
A tetracycline resistant E. coli strain containing tetA and tetR on the chromosome was constructed and cultured in the presence of increasing concentrations of tetracycline. Expression of tetR and tetA was measured at four time points in different growth phases by quantitative real-time PCR. The TetA-producing E. coli exhibited prolonged lag phase with increasing concentrations of tetracycline, while expression of tetA and tetR increased and decreased, respectively, with increasing tetracycline concentration. The levels of tetA and tetR mRNA varied depending on growth phase, resulting in a gradual decrease of the tetA/tetR ratio from approximately 4 in the lag phase to approximately 2 in the stationary phase.
This study shows that the expression of tetR and tetA is tetracycline concentration- and growth phase-dependent, contributing to improved understanding of the relationships between E. coli growth, tetracycline exposure and expression of tetracycline resistance.
Based on density functional theory calculations, kinetic measurements, microkinetic and Monte Carlo simulations, thermogravimetric analysis (TGA) experiments, extended X-ray absorption spectroscopy ...(EXAFS) measurements, and experimental results from the literature, we present a detailed and comprehensive mechanistic picture of the steam reforming process on a Ni catalyst. The complete potential energy diagram for the full reaction is presented and compared to experiments. Structures, energies of all reaction intermediates, and activation barriers are identified. We conclude that there are at least two kinds of active sites with different reactivities for steam reforming: a more active one associated with defect (step) sites, and a less active one associated with close-packed facets. It is further suggested that the nucleation of graphite is initiated at the step sites. We show that additives like potassium, sulfur, and gold preferentially bind to the step sites of Ni, and on this basis it is suggested that the promotion by these additives in terms of a higher tolerance toward graphite formation involves the same basic mechanism: blocking of the step sites.
8000 years ago, prior to Neolithic agriculture, Europe was mostly a wooded continent. Since then, its forest cover has been progressively fragmented, so that today it covers less than half of ...Europe's land area, in many cases having been cleared to make way for fields and pasture-land. Establishing the origin of Europe's current, more open land-cover mosaic requires a long-term perspective, for which pollen analysis offers a key tool. In this study we utilise and compare three numerical approaches to transforming pollen data into past forest cover, drawing on >1000
C-dated site records. All reconstructions highlight the different histories of the mixed temperate and the northern boreal forests, with the former declining progressively since ~6000 years ago, linked to forest clearance for agriculture in later prehistory (especially in northwest Europe) and early historic times (e.g. in north central Europe). In contrast, extensive human impact on the needle-leaf forests of northern Europe only becomes detectable in the last two millennia and has left a larger area of forest in place. Forest loss has been a dominant feature of Europe's landscape ecology in the second half of the current interglacial, with consequences for carbon cycling, ecosystem functioning and biodiversity.
Purpose
Previous research has identified social support to be associated with risk of posttraumatic stress disorder (PTSD) symptoms among military personnel. While the lack of social support ...influences PTSD symptomatology, it is unknown how changes in perceived social support affect the PTSD symptom level in the aftermath of deployment. Furthermore, the influence of specific sources of social support from pre- to post-deployment on level of PTSD symptoms is unknown. We aim to examine how changes in perceived social support (overall and from specific sources) from pre- to 2.5 year post-deployment are associated with the level of post-deployment PTSD symptoms.
Methods
Danish army military personnel deployed to Afghanistan in 2009 and 2013 completed questionnaires at pre-deployment and at 2.5 year post-deployment measuring perceived social support and PTSD symptomatology and sample characteristics of the two cohorts. Data were analyzed using univariate and multivariate nominal logistic regression.
Results
Negative changes in perceived social support from pre- to post-deployment were associated with both moderate (OR 1.99, CI 1.51–2.57) and high levels (OR 2.71, CI 1.94–3.78) of PTSD symptoms 2.5 year post-deployment (adjusted analysis). Broadly, the same direction was found for specific sources of social support and level of PTSD symptoms. In the adjusted analyses, pre-deployment perceived social support and military rank moderated the associations.
Conclusions
Deterioration in perceived social support (overall and specific sources) from pre- to 2.5 year post-deployment increases the risk of an elevated level of PTSD symptoms 2.5 year post-deployment.
The combination of vitrinite reflectance, apatite fission track and present‐day borehole temperature data is very useful when performing tectonic and thermal reconstructions in sedimentary basins ...which, in turn, are essential for assessing risk in hydrocarbon exploration and for testing hypotheses of basin evolution. Releasing the full potential of the combined data set requires that the predictive models are accurate in themselves. Here, we calibrate a new kinetic vitrinite reflectance model ‘basin%Ro’ using borehole data from a number of sedimentary basins and vitrinite reflectance data from laboratory maturation experiments. The entire data set is inverted for the kinetic parameters of the reflectance model under consideration of uncertainty in the temperature histories of the calibration samples. The method is not sensitive to inconsistent calibration data, which are revealed by significant corrections to the temperature histories. The performance of the model is tested on independent well data from the East China Sea and the Nova Scotian Shelf. The widely used easy%Ro‐model overestimates vitrinite reflectance in the interval 0.5–1.7% Ro by up to 0.35%. Delimiting of oil generating intervals by prediction of vitrinite reflectance may lead to significant underestimation of the generative potential, which may call for a revision of some petroleum systems. The overestimation by easy%Ro may have fuelled the idea of pressure retardation of vitrinite reflectance evolution under sedimentary basin conditions, where pressures in fact are too low for this to be important.
The growing literature conceptualizing mental disorders like posttraumatic stress disorder (PTSD) as networks of interacting symptoms faces three key challenges. Prior studies predominantly used (a) ...small samples with low power for precise estimation, (b) nonclinical samples, and (c) single samples. This renders network structures in clinical data, and the extent to which networks replicate across data sets, unknown. To overcome these limitations, the present cross-cultural multisite study estimated regularized partial correlation networks of 16 PTSD symptoms across four data sets of traumatized patients receiving treatment for PTSD (total N = 2,782). Despite differences in culture, trauma type, and severity of the samples, considerable similarities emerged, with moderate to high correlations between symptom profiles (0.43–0.82), network structures (0.62–0.74), and centrality estimates (0.63–0.75). We discuss the importance of future replicability efforts to improve clinical psychological science and provide code, model output, and correlation matrices to make the results of this article fully reproducible.
Abstract Background Approximately 30% of ischemic strokes have an unknown cause. Increased atrial ectopy (AE) increases the risk of atrial fibrillation (AF), but the risk of stroke in patients with ...increased AE is unknown. Objectives This study aimed to examine whether increased AE and short atrial runs increase the risk of stroke beyond incident AF. Methods Data were collected during a 15-year follow-up of the Copenhagen Holter Study cohort with 678 men and women between 55 and 75 years of age, with no earlier history of cardiovascular disease, stroke, or AF. Study subjects underwent 48-h ambulatory electrocardiography, fasting blood tests, and clinical examination. Excessive supraventricular ectopic activity (ESVEA) was defined as the presence of either ≥30 premature atrial contractions (PACs)/hour daily or any runs of ≥20 PACs. Results Ninety-nine subjects (15%) demonstrated ESVEA. After adjusting for baseline risk factors, ESVEA was associated with ischemic stroke when censoring subjects at time of AF (hazard ratio HR: 1.96; 95% confidence interval CI: 1.10 to 3.49) or when modeling AF as a time-varying exposure (HR: 2.00; 95% CI: 1.16 to 3.45). Among subjects with ESVEA who developed a stroke, 14.3% had diagnosed AF before their stroke. The incidence of stroke in subjects with ESVEA and a CHA2 DS2 -VASc (congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, previous stroke or transient ischemic attack, vascular disease, age 65 to 74 years, female) score of ≥2 was 2.4% per year, comparable to the risk observed in AF. In day-to-day analysis, ESVEA was a consistent finding. Conclusions ESVEA was associated with an increased risk of ischemic stroke beyond manifest AF in this middle-aged and older population. Stroke was more often the first clinical presentation, rather than AF, in these study subjects.
The height of mountain ranges reflects the balance between tectonic rock uplift, crustal strength and surface denudation. Tectonic deformation and surface denudation are interdependent, however, and ...feedback mechanisms—in particular, the potential link to climate—are subjects of intense debate. Spatial variations in fluvial denudation rate caused by precipitation gradients are known to provide first-order controls on mountain range width, crustal deformation rates and rock uplift. Moreover, limits to crustal strength are thought to constrain the maximum elevation of large continental plateaus, such as those in Tibet and the central Andes. There are indications that the general height of mountain ranges is also directly influenced by the extent of glaciation through an efficient denudation mechanism known as the glacial buzzsaw. Here we use a global analysis of topography and show that variations in maximum mountain height correlate closely with climate-controlled gradients in snowline altitude for many high mountain ranges across orogenic ages and tectonic styles. With the aid of a numerical model, we further demonstrate how a combination of erosional destruction of topography above the snowline by glacier-sliding and commensurate isostatic landscape uplift caused by erosional unloading can explain observations of maximum mountain height by driving elevations towards an altitude window just below the snowline. The model thereby self-consistently produces the hypsometric signature of the glacial buzzsaw, and suggests that differences in the height of mountain ranges mainly reflect variations in local climate rather than tectonic forces.
Despite several years of research and attempts to develop prognostic models a considerable fraction of stage II colon cancer patients will experience relapse within few years from their operation. ...The aim of the present study was to investigate the prognostic importance of miRNA-21 (miR-21), quantified by in situ hybridisation, in a unique, large population-based cohort.
The study included 764 patients diagnosed with stage II colon cancer in Denmark in the year 2003. One section from a representative paraffin-embedded tumour tissue specimen from each patient was processed for analysis of miR-21 and quantitatively assessed by image analysis.
The miR-21 signal was predominantly observed in fibroblast-like cells located in the stromal compartment of the tumours. We found that patients expressing high levels of miR-21 had significantly inferior recurrence-free cancer-specific survival (RF-CSS): HR=1.26; 95% CI: 1.15-1.60; P<0.001. In Cox regression analysis, a high level of miR-21 retained its prognostic importance and was found to be significantly related to poor RF-CSS: HR=1.41; 95% CI: 1.19-1.67; P<0.001.
The present study showed that increasing miR-21 expression levels were significantly correlated to decreasing RF-CSS. Further investigations of the clinical importance of miR-21 in the selection of high-risk stage II colon cancer patients are merited.
Rationale
Dopaminergic dysfunction is implicated in disorders of impulsivity and inattention. The rodent continuous performance test (rCPT) has been used to quantify changes in attention and ...impulsivity.
Objective
To examine the roles of dopamine receptors in attention and impulsivity behaviours measured in the rCPT variable stimulus duration (vSD) and the variable intertrial interval schedules (vITI) using DA receptor antagonists.
Methods
Two cohorts of 35 and 36 female C57BL/6JRj mice were examined separately in the rCPT, vSD, and vITI schedules, respectively. Both cohorts received antagonists of the following receptors: D
1/5
(SCH23390, SCH: 0.01, 0.02, 0.04 mg/kg) and D
2/3
(raclopride, RAC 0.03, 0.10, 0.30 mg/kg) in consecutive balanced Latin square designs with flanking reference measurements. The antagonists were subsequently examined for effects on locomotor activity.
Results
SCH showed similar effects in both schedules, and the effects were reference-dependent in the vITI schedule. SCH reduced responding, but improved response accuracy, impulsivity, discriminability, and locomotor activity. RAC showed mixed effects on responsivity, but improved accuracy and discriminability. The discriminability improvement was driven by an increase in hit rate in the vITI schedule and a reduction in false alarm rate in the vSD schedule. RAC also decreased locomotor activity.
Conclusion
Both D
1/5
and D
2/3
receptor antagonism reduced responding, but the outcome on discriminability differed, stemming from individual effects on hit and false alarm rate, and the weight of omissions within the calculation. The effects of SCH and RAC suggest that endogenous DA increases responding and impulsivity, but reduces accuracy and shows mixed effects on discriminability.
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