Adaptation of Root Function by Nutrient-Induced Plasticity of Endodermal Differentiation.

Plant roots forage the soil for minerals whose concentrations can be orders of magnitude away from those required for plant cell function. Selective uptake in multicellular organisms critically requires epithelia with extracellular diffusion barriers. In plants, such a barrier is provided by the endodermis and its Casparian strips-cell wall impregnations analogous to animal tight and adherens junctions. Interestingly, the endodermis undergoes secondary differentiation, becoming coated with hydrophobic suberin, presumably switching from an actively absorbing to a protective epithelium. Here, we show that suberization responds to a wide range of nutrient stresses, mediated by the stress hormones abscisic acid and ethylene. We reveal a striking ability of the root to not only regulate synthesis of suberin, but also selectively degrade it in response to ethylene. Finally, we demonstrate that changes in suberization constitute physiologically relevant, adaptive responses, pointing to a pivotal role of the endodermal membrane in nutrient homeostasis.

CO2 utilization in the perspective of industrial ecology, an overview

Carbon dioxide emissions from anthropic activities have accumulated in the atmosphere in excess of 800 Gigatons since preindustrial times, and are continuously increasing. Among other strategies, CO2 capture and storage is one option to mitigate the emissions from large point sources. In addition, carbon dioxide extraction from ambient air is assessed to reduce the atmospheric concentration of CO2. Both direct and indirect (through photosynthesis) pathways are possible. Geological sequestration has significant disadvantages (high cost, low public acceptance, long term uncertainty) whereas carbon dioxide recycling (or utilization) is more consistent with the basic principle of industrial ecology, almost closing material cycles. In this article, a series of technologies for CO2 capture and valorization is described as integrated and optimized pathways. This integration increases the environmental and economic benefits of each technology. Depending on the source of carbon dioxide, appropriate capture and valorization processes are evaluated based on material and energy constraints.

La dépendance à l'égard de l'environnement lors de lésions cérébrales: conduites d'imitation, de préhension et d'utilisation [Environmental dependence in brain lesions: imitative behavior, prehension and utilization].

This paper reviews the literature on clinical signs such as imitation behavior, grasp reaction, manipulation of tools, utilization behavior, environmental dependency, hyperlexia, hypergraphia and echolalia. Some aspects of this semiology are of special interest because they refer to essential notions such as free-will and autonomy.

Correlation of wear in vivo and six laboratory wear methods.

OBJECTIVE: We examined the correlation between clinical wear rates of restorative materials and enamel (TRAC Research Foundation, Provo, USA) and the results of six laboratory test methods (ACTA, Alabama (generalized, localized), Ivoclar (vertical, volumetric), Munich, OHSU (abrasion, attrition), Zurich). METHODS: Individual clinical wear data were available from clinical trials that were conducted by TRAC Research Foundation (formerly CRA) together with general practitioners. For each of the n=28 materials (21 composite resins for intra-coronal restorations [20 direct and 1 indirect], 5 resin materials for crowns, 1 amalgam, enamel) a minimum of 30 restorations had been placed in posterior teeth, mainly molars. The recall intervals were up to 5 years with the majority of materials (n=27) being monitored, however, only for up to 2 years. For the laboratory data, the databases MEDLINE and IADR abstracts were searched for wear data on materials which were also clinically tested by TRAC Research Foundation. Only those data for which the same test parameters (e.g. number of cycles, loading force, type of antagonist) had been published were included in the study. A different quantity of data was available for each laboratory method: Ivoclar (n=22), Zurich (n=20), Alabama (n=17), OHSU and ACTA (n=12), Munich (n=7). The clinical results were summed up in an index and a linear mixed model was fitted to the log wear measurements including the following factors: material, time (0.5, 1, 2 and 3 years), tooth (premolar/molar) and gender (male/female) as fixed effects, and patient as random effect. Relative ranks were created for each material and method; the same was performed with the clinical results. RESULTS: The mean age of the subjects was 40 (±12) years. The materials had been mostly applied in molars (81%) and 95% of the intracoronal restorations were Class II restorations. The mean number of individual wear data per material was 25 (range 14-42). The mean coefficient of variation of clinical wear data was 53%. The only significant correlation was reached by OHSU (abrasion) with a Spearman r of 0.86 (p=0.001). Zurich, ACTA, Alabama generalized wear and Ivoclar (volume) had correlation coefficients between 0.3 and 0.4. For Zurich, Alabama generalized wear and Munich, the correlation coefficient improved if only composites for direct use were taken into consideration. The combination of different laboratory methods did not significantly improve the correlation. SIGNIFICANCE: The clinical wear of composite resins is mainly dependent on differences between patients and less on the differences between materials. Laboratory methods to test conventional resins for wear are therefore less important, especially since most of them do not reflect the clinical wear.

Challenging recommended oral and intravenous voriconazole doses for improved efficacy and safety: population pharmacokinetics-based analysis of adult patients with invasive fungal infections.

BACKGROUND: Recommended oral voriconazole (VRC) doses are lower than intravenous doses. Because plasma concentrations impact efficacy and safety of therapy, optimizing individual drug exposure may improve these outcomes. METHODS: A population pharmacokinetic analysis (NONMEM) was performed on 505 plasma concentration measurements involving 55 patients with invasive mycoses who received recommended VRC doses. RESULTS: A 1-compartment model with first-order absorption and elimination best fitted the data. VRC clearance was 5.2 L/h, the volume of distribution was 92 L, the absorption rate constant was 1.1 hour(-1), and oral bioavailability was 0.63. Severe cholestasis decreased VRC elimination by 52%. A large interpatient variability was observed on clearance (coefficient of variation [CV], 40%) and bioavailability (CV 84%), and an interoccasion variability was observed on bioavailability (CV, 93%). Lack of response to therapy occurred in 12 of 55 patients (22%), and grade 3 neurotoxicity occurred in 5 of 55 patients (9%). A logistic multivariate regression analysis revealed an independent association between VRC trough concentrations and probability of response or neurotoxicity by identifying a therapeutic range of 1.5 mg/L (>85% probability of response) to 4.5 mg/L (<15% probability of neurotoxicity). Population-based simulations with the recommended 200 mg oral or 300 mg intravenous twice-daily regimens predicted probabilities of 49% and 87%, respectively, for achievement of 1.5 mg/L and of 8% and 37%, respectively, for achievement of 4.5 mg/L. With 300-400 mg twice-daily oral doses and 200-300 mg twice-daily intravenous doses, the predicted probabilities of achieving the lower target concentration were 68%-78% for the oral regimen and 70%-87% for the intravenous regimen, and the predicted probabilities of achieving the upper target concentration were 19%-29% for the oral regimen and 18%-37% for the intravenous regimen. CONCLUSIONS: Higher oral than intravenous VRC doses, followed by individualized adjustments based on measured plasma concentrations, improve achievement of the therapeutic target that maximizes the probability of therapeutic response and minimizes the probability of neurotoxicity. These findings challenge dose recommendations for VRC.

Accuracy of a new transmittance-reflectance pulse oximetry sensor in critically ill neonates.

OBJECTIVE: To test the accuracy of a new pulse oximeter sensor based on transmittance and reflectance. This sensor makes transillumination of tissue unnecessary and allows measurements on the hand, forearm, foot, and lower limb. DESIGN: Prospective, open, nonrandomized criterion standard study. SETTING: Neonatal intensive care unit, tertiary care center. PATIENTS: Sequential sample of 54 critically ill neonates (gestational age 27 to 42 wks; postnatal age 1 to 28 days) with arterial catheters in place. MEASUREMENTS AND MAIN RESULTS: A total of 99 comparisons between pulse oximetry and arterial saturation were obtained. Comparison of femoral or umbilical arterial blood with transcutaneous measurements on the lower limb (n = 66) demonstrated an excellent correlation (r2 = .96). The mean difference was +1.44% +/- 3.51 (SD) % (range -11% to +8%). Comparison of the transcutaneous values with the radial artery saturation from the corresponding upper limb (n = 33) revealed a correlation coefficient of 0.94 with a mean error of +0.66% +/- 3.34% (range -6% to +7%). The mean difference between noninvasive and invasive measurements was least with the test sensor on the hand, intermediate on the calf and arm, and greatest on the foot. The mean error and its standard deviation were slightly larger for arterial saturation values < 90% than for values > or = 90%. CONCLUSION: Accurate pulse oximetry saturation can be acquired from the hand, forearm, foot, and calf of critically ill newborns using this new sensor.

Skeletal Muscle Mitochondrial and Lipid Droplet Volume Density: Validity of Electron Microscopy Point-counting Measurements

Mitochondrial (M) and lipid droplet (L) volume density (vd) are often used in exercise research. Vd is the volume of muscle occupied by M and L. The means of calculating these percents are accomplished by applying a grid to a 2D image taken with transmission electron microscopy; however, it is not known which grid best predicts these values. PURPOSE: To determine the grid with the least variability of Mvd and Lvd in human skeletal muscle. METHODS: Muscle biopsies were taken from vastus lateralis of 10 healthy adults, trained (N=6) and untrained (N=4). Samples of 5-10mg were fixed in 2.5% glutaraldehyde and embedded in EPON. Longitudinal sections of 60 nm were cut and 20 images were taken at random at 33,000x magnification. Vd was calculated as the number of times M or L touched two intersecting grid lines (called a point) divided by the total number of points using 3 different sizes of grids with squares of 1000x1000nm sides (corresponding to 1µm2), 500x500nm (0.25µm2) and 250x250nm (0.0625µm2). Statistics included coefficient of variation (CV), 1 way-BS ANOVA and spearman correlations. RESULTS: Mean age was 67 ± 4 yo, mean VO2peak 2.29 ± 0.70 L/min and mean BMI 25.1 ± 3.7 kg/m2. Mean Mvd was 6.39% ± 0.71 for the 1000nm squares, 6.01% ± 0.70 for the 500nm and 6.37% ± 0.80 for the 250nm. Lvd was 1.28% ± 0.03 for the 1000nm, 1.41% ± 0.02 for the 500nm and 1.38% ± 0.02 for the 250nm. The mean CV of the three grids was 6.65% ±1.15 for Mvd with no significant differences between grids (P>0.05). Mean CV for Lvd was 13.83% ± 3.51, with a significant difference between the 1000nm squares and the two other grids (P<0.05). The 500nm squares grid showed the least variability between subjects. Mvd showed a positive correlation with VO2peak (r = 0.89, p < 0.05) but not with weight, height, or age. No correlations were found with Lvd. CONCLUSION: Different size grids have different variability in assessing skeletal muscle Mvd and Lvd. The grid size of 500x500nm (240 points) was more reliable than 1000x1000nm (56 points). 250x250nm (1023 points) did not show better reliability compared with the 500x500nm, but was more time consuming. Thus, choosing a grid with square size of 500x500nm seems the best option. This is particularly relevant as most grids used in the literature are either 100 points or 400 points without clear information on their square size.

Separate neuronal and glial Na+,K+-ATPase isoforms regulate glucose utilization in response to membrane depolarization and elevated extracellular potassium.

The role of cell type-specific Na+,K+-ATPase isozymes in function-related glucose metabolism was studied using differentiated rat brain cell aggregate cultures. In mixed neuron-glia cultures, glucose utilization, determined by measuring the rate of radiolabeled 2-deoxyglucose accumulation, was markedly stimulated by the voltage-dependent sodium channel agonist veratridine (0.75 micromol/L), as well as by glutamate (100 micromol/L) and the ionotropic glutamate receptor agonist N-methyl-D-aspartate (NMDA) (10 micromol/L). Significant stimulation also was elicited by elevated extracellular potassium (12 mmol/L KCl), which was even more pronounced at 30 mmol/L KCl. In neuron-enriched cultures, a similar stimulation of glucose utilization was obtained with veratridine, specific ionotropic glutamate receptor agonists, and 30 mmol/L but not 12 mmol/L KCl. The effects of veratridine, glutamate, and NMDA were blocked by specific antagonists (tetrodotoxin, CNQX, or MK801, respectively). Low concentrations of ouabain (10(-6) mol/L) prevented stimulation by the depolarizing agents but reduced only partially the response to 12 mmol/L KCl. Together with previous data showing cell type-specific expression of Na+,K+-ATPase subunit isoforms in these cultures, the current results support the view that distinct isoforms of Na+,K+-ATPase regulate glucose utilization in neurons in response to membrane depolarization, and in glial cells in response to elevated extracellular potassium.

Effect of diets high or low in unavailable and slowly digestible carbohydrates on the pattern of 24-h substrate oxidation and feelings of hunger in humans.

BACKGROUND: The pattern of substrate utilization with diets containing a high or a low proportion of unavailable and slowly digestible carbohydrates may constitute an important factor in the control, time course, and onset of hunger in humans. OBJECTIVE: We tested the hypothesis that isoenergetic diets differing only in their content of unavailable carbohydrates would result in different time courses of total, endogenous, and exogenous carbohydrate oxidation rates. DESIGN: Two diets with either a high (H diet) or a low (L diet) content of unavailable carbohydrates were fed to 14 healthy subjects studied during two 24-h periods in a metabolic chamber. Substrate utilization was assessed by whole-body indirect calorimetry. In a subgroup of 8 subjects, endogenous and exogenous carbohydrate oxidation were assessed by prelabeling the body glycogen stores with [(13)C]carbohydrate. Subjective feelings of hunger were estimated with use of visual analogue scales. RESULTS: Total energy expenditure and substrate oxidation did not differ significantly between the 2 diets. However, there was a significant effect of diet (P: = 0.03) on the carbohydrate oxidation pattern: the H diet elicited a lower and delayed rise of postprandial carbohydrate oxidation and was associated with lower hunger feelings than was the L diet. The differences in hunger scores between the 2 diets were significantly associated with the differences in the pattern of carbohydrate oxidation among diets (r = -0.67, P: = 0. 006). Exogenous and endogenous carbohydrate oxidation were not significantly influenced by diet. CONCLUSIONS: The pattern of carbohydrate utilization is involved in the modulation of hunger feelings. The greater suppression of hunger after the H diet than after the L diet may be helpful, at least over the short term, in individuals attempting to better control their food intake.

Une IgA à coefficient de sédimentation 11 S dans les sécrétions externes de l'espèce bovine

The sedimentation coefficient of a secretory IgA found in bovine colostrum and saliva is compared with that of IgG and IgM from the same colostrum. The IgA fraction gives a value of 10.8 S, whereas the major part of the IgG has a value of 7.1 S and the IgM 19.2 S. The sedimentation coefficient of the free secretory piece has also been determined: its value is 4.95 S.

Physiology and transcriptome of the polycyclic aromatic hydrocarbon-degrading Sphingomonas sp. LH128 after long-term starvation.

The survival, physiology and gene expression profile of the phenanthrene-degrading Sphingomonas sp. LH128 was examined after an extended period of complete nutrient starvation and compared with a non-starved population that had been harvested in exponential phase. After 6 months of starvation in an isotonic solution, only 5 % of the initial population formed culturable cells. Microscopic observation of GFP fluorescent cells, however, suggested that a larger fraction of cells (up to 80 %) were still alive and apparently had entered a viable but non-culturable (VBNC) state. The strain displayed several cellular and genetic adaptive strategies to survive long-term starvation. Flow cytometry, microscopic observation and fatty acid methyl ester (FAME) analysis showed a reduction in cell size, a change in cell shape and an increase in the degree of membrane fatty acid saturation. Transcriptome analysis showed decreased expression of genes involved in ribosomal protein biosynthesis, chromosomal replication, cell division and aromatic catabolism, increased expression of genes involved in regulation of gene expression and efflux systems, genetic translocations, and degradation of rRNA and fatty acids. Those phenotypic and transcriptomic changes were not observed after 4 h of starvation. Despite the starvation situation, the polycyclic aromatic hydrocarbon (PAH) catabolic activity was immediate upon exposure to phenanthrene. We conclude that a large fraction of cells maintain viability after an extended period of starvation apparently due to tuning the expression of a wide variety of cellular processes. Due to these survival attributes, bacteria of the genus Sphingomonas, like strain LH128, could be considered as suitable targets for use in remediation of nutrient-poor PAH-contaminated environments.

Population pharmacokinetic modelling and evaluation of different dosage regimens for darunavir and ritonavir in HIV-infected individuals.

OBJECTIVES: Darunavir is a protease inhibitor that is administered with low-dose ritonavir to enhance its bioavailability. It is prescribed at standard dosage regimens of 600/100 mg twice daily in treatment-experienced patients and 800/100 mg once daily in naive patients. A population pharmacokinetic approach was used to characterize the pharmacokinetics of both drugs and their interaction in a cohort of unselected patients and to compare darunavir exposure expected under alternative dosage regimens. METHODS: The study population included 105 HIV-infected individuals who provided darunavir and ritonavir plasma concentrations. Firstly, a population pharmacokinetic analysis for darunavir and ritonavir was conducted, with inclusion of patients' demographic, clinical and genetic characteristics as potential covariates (NONMEM(®)). Then, the interaction between darunavir and ritonavir was studied while incorporating levels of both drugs into different inhibitory models. Finally, model-based simulations were performed to compare trough concentrations (Cmin) between the recommended dosage regimen and alternative combinations of darunavir and ritonavir. RESULTS: A one-compartment model with first-order absorption adequately characterized darunavir and ritonavir pharmacokinetics. The between-subject variability in both compounds was important [coefficient of variation (CV%) 34% and 47% for darunavir and ritonavir clearance, respectively]. Lopinavir and ritonavir exposure (AUC) affected darunavir clearance, while body weight and darunavir AUC influenced ritonavir elimination. None of the tested genetic variants showed any influence on darunavir or ritonavir pharmacokinetics. The simulations predicted darunavir Cmin much higher than the IC50 thresholds for wild-type and protease inhibitor-resistant HIV-1 strains (55 and 550 ng/mL, respectively) under standard dosing in >98% of experienced and naive patients. Alternative regimens of darunavir/ritonavir 1200/100 or 1200/200 mg once daily also had predicted adequate Cmin (>550 ng/mL) in 84% and 93% of patients, respectively. Reduction of darunavir/ritonavir dosage to 600/50 mg twice daily led to a 23% reduction in average Cmin, still with only 3.8% of patients having concentrations below the IC50 for resistant strains. CONCLUSIONS: The important variability in darunavir and ritonavir pharmacokinetics is poorly explained by clinical covariates and genetic influences. In experienced patients, treatment simplification strategies guided by drug level measurements and adherence monitoring could be proposed.

Variability of gait patterns during unconstrained walking assessed by satellite positioning (GPS).

It is established that the ratio between step length (SL) and step frequency (SF) is constant over a large range of walking speed. However, few data are available about the spontaneous variability of this ratio during unconstrained outdoor walking, in particular over a sufficient number of steps. The purpose of the present study was to assess the inter- and intra-subject variability of spatio-temporal gait characteristics [SL, SF and walk ratio (WR=SL/SF)] while walking at different freely selected speeds. Twelve healthy subjects walked three times along a 100-m athletic track at: (1). a slower than preferred speed, (2). preferred speed and (3). a faster than preferred speed. Two professional GPS receivers providing 3D positions assessed the walking speed and SF with high precision (less than 0.5% error). Intra-subject variability was calculated as the variation among eight consecutive 5-s samples. WR was found to be constant at preferred and fast speeds [0.41 (0.04) m.s and 0.41 (0.05) m.s respectively] but was higher at slow speeds [0.44 (0.05) m.s]. In other words, between slow and preferred speed, the speed increase was mediated more by a change in SF than SL. The intra-subject variability of WR was low under preferred [CV, coefficient of variation = 1.9 (0.6)%] and fast [CV=1.8 (0.5)%] speed conditions, but higher under low speed condition [CV=4.1 (1.5)%]. On the other hand, the inter-subject variability of WR was 11%, 10% and 12% at slow, preferred and fast walking speeds respectively. It is concluded that the GPS method is able to capture basic gait parameters over a short period of time (5 s). A specific gait pattern for slow walking was observed. Furthermore, it seems that the walking patterns in free-living conditions exhibit low intra-individual variability, but that there is substantial variability between subjects.

Oxidative and nonoxidative glucose metabolism following graded doses of oral glucose in man.

The oxidative and nonoxidative glucose metabolism represent the two major mechanisms of the utilization of a glucose load. Eight normal subjects were administered oral loads of 50, 100 and 150 g glucose and gas exchange measurements were performed for eight hours by means of computerized continuous indirect calorimetry. The glycemic peaks were almost identical with all three doses with a rise to between 141 and 147 mg/dl at 60 min. The fall back to basal level was reached later with the high than with the low glucose doses. The glucose oxidation rate rose to values between 223 and 253 mg/min after the three glucose doses, but while falling immediately after the peak at 120 min following the 50 g load, the glucose oxidation rate remained at its maximum rate until 210 min for the 100 g glucose load and plateaued up to 270 min for the 150 g glucose dose. The oxidation rates then fell gradually to reach basal levels at 270, 330 and 420 min according to the increasing size of the load. Altogether 55 +/- 3 g glucose were oxidized during the 8 hours following the 50 g glucose load, 75 +/- 3 g after the 100 g load and 80 +/- 5 g after the 150 g load. The nonoxidative glucose disposal, which corresponds essentially to glucose storage, varied according to the size of the glucose load, with uptakes of 20 +/- 1, 60 +/- 1 and 110 +/- 1 g glucose 180 min after the 50, 100 and 150 g glucose loads respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

A cross-cultural study of the higher-order structures underlying personality disorders in French-speaking Africa and Switzerland

Most studies about the higher-order dimensions to be considered in order to parsimoniously describe Personality Disorders (PDs) have identified between two and four factors but there is still no consensus about their exact number. In this context, the cultural stability of these structures might be a criterion to be considered. The aim of this study was to identify stable higher-order structures of PD traits in a French-speaking African and Swiss sample (N = 2,711). All subject completed the IPDE screening questionnaire. Using Everett's criterion and conducting a series of principal component analyses, a cross-culturally stable two- and four-factor structure were identified, associated with a total congruence coefficient of respectively .98 and .94 after Procrustes rotation. Moreover, these two structures were also highly replicable across the four African regions considered, North Africa, West Africa, Central Africa, and Mauritius, with a mean total congruence coefficient of respectively .97 and .87. The four-factor structure presented the advantage of being similar to Livesely's four components and of describing the ten PDs more accurately.