Relationship between cellular response and behavioral variability in bacterial chemotaxis

Over the last decades, bacterial chemotaxis in Escherichia coli has emerged as a canonical system for the study of signal transduction. A remarkable feature of this system is the coexistence of a robust adaptive behavior observed at the population level with a large fluctuating behavior in single cells [Korobkova E, Emonet T, Vilar JMG, Shimizu TS, Cluzel P (2004) Nature 428:574-578]. Using a unified stochastic model, we demonstrate that this coexistence is not fortuitous but a direct consequence of the architecture of this adaptive system. The methylation and demethylation cycles that regulate the activity of receptor-kinase complexes are ultrasensitive because they operate outside the region of first-order kinetics. As a result, the receptor-kinase that governs cellular behavior exhibits a sigmoidal activation curve. We propose that the steepness of this kinase activation curve simultaneously controls the behavioral variability in nonstimulated individual bacteria and the duration of the adaptive response to small stimuli. We predict that the fluctuating behavior and the chemotactic response of individual cells both peak within the transition region of this sigmoidal curve. Large-scale simulations of digital bacteria suggest that the chemotaxis network is tuned to simultaneously maximize both the random spread of cells in the absence of nutrients and the cellular response to gradients of attractant. This study highlights a fundamental relation from which the behavioral variability of nonstimulated cells is used to infer the timing of the cellular response to small stimuli.     

Ventricular Conduction Defects After Transcatheter Aortic Valve Implantation: A Single‐Institute Analysis

Patients with aortic stenosis tend to develop ventricular conduction problems, which are known adverse events following transcatheter aortic valve implantation (TAVI). Changes in ventricular conduction status after TAVI were analyzed in 195 consecutive patients from a single institute registered in FRANCE2 between February 2010 and June 2012. Among the 195 patients, 29 had a prior pacemaker implantation (+PM) and 6 had acute catastrophic hemodynamics that made a full electrocardiogram (ECG) unavailable. Among the remaining 160, PM was newly required in 28 (17.5%, PM+) but not in 132 (PM?), which included 21 (13.1%) who developed new left bundle branch block (BBB), 12 (7.5%) had right BBB, and 99 (61.9%) had no change. While PM requirement had no correlation with preoperative factors, there was significant association with the development of right BBB with Edwards Sapien/XT (P = 0.003), and new left BBB (P = 0.012) and complete heart block requiring PM with CoreValve (22.6% vs. Edwards Sapien/XT, 7.4%, P = 0.016). Whereas postoperative survival regarding PM status (+PM, PM+, PM–), vascular access, valve size or type showed no difference, delayed heart block (n = 12, Day 2 or later) was associated with poor survival (P = 0.038) compared with the remaining PM+ patients with earlier onset (n = 16, Day 0 or 1). As a result, PM+ patients (n = 28) had significantly longer intensive care unit (ICU) stay and hospitalization than PM? or +PM patients. The results suggest that ventricular conduction problems requiring PM occurred more frequently after TAVI (17.5%) than with usual surgical replacement. Nonetheless, conduction problems failed to influence postoperative survival for up to 3 years on average with use of PM, but therefore did increase medical costs.     

Reliability analysis for manual measurement of coronal plane deformity in adolescent scoliosis. Are 30?×?90?cm plain films better than digitized small films?

For several years, digitized small radiographs are used to measure Cobb angle in idiopathic scoliosis. The interobserver and intraobserver Cobb angle measurement variability associated with small radiographs were compared with measurement variability associated with the long-cassette radiographs. Twenty adolescent patients with a double major idiopathic scoliosis had erect full-spine p-A radiographs and Cobb angle measurements performed by eight different observers on a 30 x 90 cm plain-film radiograph and a digitized 14 x 42 cm image. Inter-observer and intra-observer reliability using each techniques were assessed using a paired t-test, Spearman rank correlation study and intraclass correlation coefficients. The angle variability between small film and plain-film measurements was assessed using the same methods. Intra-observer and inter-observer study showed good reliability using both techniques. The comparison between small films and plain-films measurements showed very good agreement with an intraclass correlation coefficient of 95% and confidence interval between 0.962 and 0.972. In our study, Cobb angle determination was not found to vary significantly with film size. The small film image used for full-spine radiographs in our institution allows manual Cobb angle measurements to be performed. A study is currently conducted in our institution to determine if a computer-assisted measurement method significantly improves Cobb angle measurements reliability in routine practice compared with manual measurements of Cobb angles on small films.     

Comparison of intraocular treatment of DMTU and SOD following retinal ischemia in rats.

The effect of intravitreal injections of DMTU (dimethylthiourea) and SOD (superoxide dismutase), two free radical scavengers, was evaluated in a rat model of retinal ischemia induced by elevated intraocular pressure. The drugs were administered just before or just after a 60 min ischemia. At days 2 and 7 after reperfusion, retinal recovery was evaluated by electroretinography. At day 7, layer thicknesses and cell rows were measured from histologic sections of paraffin-embedded retinas. In the vehicle-treated control group, we observed a decrease in the inner retinal layers and b-wave amplitude impairment. SOD injection (6 units/eye) protected the retina from ischemia/reperfusion injury. At day 2 after reperfusion, electroretinographic recovery was more efficient when SOD was administered just after ischemia (99%) than after pretreatment with SOD (81%) (p<0.03). In the DMTU-treated group (75 microg/eye), only the pretreatment induced significant electrophysiologic (40%) (p<0.001) and morphologic recovery.     

Multimodality imaging of percutaneous closure of the left atrial appendage

An 81-year-old woman with a past history of systemic hypertension,chronic paroxysmal atrial fibrillation, three-time     

Polyvascular subclinical atherosclerosis in familial hypercholesterolemia: The role of cholesterol burden and gender

Background and aimHeterozygous familial hypercholesterolemia (HeFH) is a genetic disease characterized by a heterogeneous phenotype. The assessment of cardiovascular (CV) risk is challenging for HeFH. Cholesterol burden (CB) allows to estimate the lifelong exposure to high levels of cholesterol. The aim of this study was to analyze the distribution of subclinical atherosclerosis and the relationship between atherosclerosis and the CB in a sample of HeFH patients, focusing on sex-related differences.Methods and Results154 asymptomatic HeFH subjects underwent coronary-artery-calcium score (CACs) and Doppler ultrasound of carotid and femoral arteries. Yearly lipid profiles and HeHF history were obtained from patients' files in order to calculate total CB. Atherosclerotic burden was defined by the presence of CACs > 0 or by the presence of carotid or femoral plaque. Study population was stratified according to gender. The prevalence of CAC, carotid and femoral atherosclerosis was of 62%, 55% and 56%, respectively. Coronary district was the least involved in women, who had a higher prevalence in carotid atherosclerosis. When two vascular districts were affected, women had an increased prevalence of femoral and carotid atherosclerosis whereas men had a higher prevalence of coronary and femoral atherosclerosis. CB correlated to the presence of atherosclerosis in any of the three vascular districts with a significant increasing trend depending on the number of affected areas.ConclusionsA polyvascular atherosclerotic burden is found in asymptomatic HeFH patients. Gender differences in the territory distribution were observed. The early and lasting exposure to high cholesterol, as expressed by CB, is a major determinant of atherosclerotic burden.     

Research directions in eco-innovation: a French perspective

The French network Eco-design of Sustainable Systems (EcoSD) has initiated collaborative research projects in order to foster collaborations between academic and industrial partners. Two projects concerning eco-innovation processes, methods and tools have been carried out between 2012 and 2014. This paper first offers a synthesis of the projects, and questions the new directions to feed research in eco-innovation for the forthcoming years. The first project concerned the perception of eco-innovation by companies. It aimed at defining the features and goals of eco-innovation compared to eco-design through a survey with 12 French industrial partners. Results confirm that eco-innovation still is an emerging topic and does not seem to be supported by any structured process. The second project made a focus on the stage of eco-evaluation and eco-selection of the most promising ideas. In order to understand the emergence of ideas with a high environmental potential, three groups of mixed academics and industrials were asked to test two methods involving mapping, selection, combination and environmental evaluation of ideas. Main results show that there is a large inter-group variability in the evaluation of the environmental potential of ideas. Lastly, three interlinked directions for research in eco-innovation are identified. The first direction deals with the eco-ideation phase, where appropriate stimulation mechanisms should be integrated to. The second direction deals with the environmental evaluation of ideas very early in the process. It is necessary to characterize the inputs and outputs from this phase, building a bridge towards a latter simplified environmental assessment. The last direction deals with the construction of an efficient eco-innovation process based on the two previous phases. The challenge is to reduce the gap between academia and industry, enabling companies to introduce an eco-innovation process into their current design process.     

Is 18F‐fluorodeoxyglucose positron emission tomography scanning a reliable way to assess disease activity in takayasu arteritis?

Objective

¹⁸F‐fluorodeoxyglucose–positron emission tomography (FDG‐PET) scanning has been proposed as a new way of assessing disease activity in Takayasu arteritis (TA), but previous studies have used the nonvalidated National Institutes of Health (NIH) global activity criteria, and thus might be biased. This study was undertaken to determine the value of PET scanning for assessment of disease activity in TA, by comparing PET scan data with clinical, biologic, and magnetic resonance imaging (MRI) data assessed separately.

Methods

Twenty‐eight patients with TA (according to the American College of Rheumatology criteria) underwent a total of 40 PET scans. Images were reviewed by 2 pairs of independent nuclear medicine physicians and assessed for pattern and intensity of vascular uptake. TA activity data were obtained within 15 days of the PET scans.

Results

PET scanning revealed abnormal vascular uptake in 47% of the 40 examinations. The uptake intensity grade was 0 in 7 scans, grade 1 in 7 scans, grade 2 in 13 scans, and grade 3 in 13 scans. Morphologic analysis was conducted by grading the pattern of the vascular uptake as diffuse (73%), segmental (20%), or focal (13%). There was a trend toward an association between clinically active disease and the semiquantitative assessment of FDG uptake (P = 0.08). We found no statistical association between levels of acute‐phase reactants and intensity of uptake. There was no significant association between the semiquantitative assessment of FDG uptake and the presence of vascular wall thickening (P = 0.23), gadolinium uptake (P = 0.73), or the presence of vascular wall edema (P = 0.56).

Conclusion

Our findings indicate that there is no association between FDG vascular uptake intensity and clinical, biologic, or MRI assessment of disease activity. Previous studies using the nonvalidated NIH global activity criteria are likely biased.