Round robin test: wear of nine dental restorative materials in six different wear simulators - supplement to the round robin test of 2005.

OBJECTIVE: The purpose of the present study was to submit the same materials that were tested in the round robin wear test of 2002/2003 to the Alabama wear method. METHODS: Nine restorative materials, seven composites (belleGlass, Chromasit, Estenia, Heliomolar, SureFil, Targis, Tetric Ceram) an amalgam (Amalcap) and a ceramic (IPS Empress) have been submitted to the Alabama wear method for localized and generalized wear. The test centre did not know which brand they were testing. Both volumetric and vertical loss had been determined with an optical sensor. After completion of the wear test, the raw data were sent to IVOCLAR for further analysis. The statistical analysis of the data included logarithmic transformation of the data, the calculation of relative ranks of each material within each test centre, measures of agreement between methods, the discrimination power and coefficient of variation of each method as well as measures of the consistency and global performance for each material. RESULTS: Relative ranks of the materials varied tremendously between the test centres. When all materials were taken into account and the test methods compared with each other, only ACTA agreed reasonably well with two other methods, i.e. OHSU and ZURICH. On the other hand, MUNICH did not agree with the other methods at all. The ZURICH method showed the lowest discrimination power, ACTA, IVOCLAR and ALABAMA localized the highest. Material-wise, the best global performance was achieved by the leucite reinforced ceramic material Empress, which was clearly ahead of belleGlass, SureFil and Estenia. In contrast, Heliomolar, Tetric Ceram and especially Chromasit demonstrated a poor global performance. The best consistency was achieved by SureFil, Tetric Ceram and Chromasit, whereas the consistency of Amalcap and Heliomolar was poor. When comparing the laboratory data with clinical data, a significant agreement was found for the IVOCLAR and ALABAMA generalized wear method. SIGNIFICANCE: As the different wear simulator settings measure different wear mechanisms, it seems reasonable to combine at least two different wear settings to assess the wear resistance of a new material.

A quantitative test of Hamilton's rule for the evolution of altruism.

The evolution of altruism is a fundamental and enduring puzzle in biology. In a seminal paper Hamilton showed that altruism can be selected for when rb - c > 0, where c is the fitness cost to the altruist, b is the fitness benefit to the beneficiary, and r is their genetic relatedness. While many studies have provided qualitative support for Hamilton's rule, quantitative tests have not yet been possible due to the difficulty of quantifying the costs and benefits of helping acts. Here we use a simulated system of foraging robots to experimentally manipulate the costs and benefits of helping and determine the conditions under which altruism evolves. By conducting experimental evolution over hundreds of generations of selection in populations with different c/b ratios, we show that Hamilton's rule always accurately predicts the minimum relatedness necessary for altruism to evolve. This high accuracy is remarkable given the presence of pleiotropic and epistatic effects as well as mutations with strong effects on behavior and fitness (effects not directly taken into account in Hamilton's original 1964 rule). In addition to providing the first quantitative test of Hamilton's rule in a system with a complex mapping between genotype and phenotype, these experiments demonstrate the wide applicability of kin selection theory.

Circadian clock-coordinated 12 Hr period rhythmic activation of the IRE1alpha pathway controls lipid metabolism in mouse liver.

The mammalian circadian clock plays a fundamental role in the liver by regulating fatty acid, glucose, and xenobiotic metabolism. Impairment of this rhythm has been shown to lead to diverse pathologies, including metabolic syndrome. Currently, it is supposed that the circadian clock regulates metabolism mostly by regulating expression of liver enzymes at the transcriptional level. Here, we show that the circadian clock also controls hepatic metabolism by synchronizing a secondary 12 hr period rhythm characterized by rhythmic activation of the IRE1alpha pathway in the endoplasmic reticulum. The absence of circadian clock perturbs this secondary clock and provokes deregulation of endoplasmic reticulum-localized enzymes. This leads to impaired lipid metabolism, resulting in aberrant activation of the sterol-regulated SREBP transcription factors. The resulting aberrant circadian lipid metabolism in mice devoid of the circadian clock could be involved in the appearance of the associated metabolic syndrome.

Evaluation of the caloric test by combining 3 response parameters.

The slow-phase velocity of nystagmus is one of the most sensitive parameters of vestibular function and is currently the standard for evaluating the caloric test. However, the assessment of this parameter requires recording the response by using nystagmography. The aim of this study was to evaluate whether frequency and duration of the caloric nystagmus, as measured by using a clinical test with Frenzel glasses, could predict the result of the recorded test. The retrospective analysis of 222 caloric test results recorded by means of electronystagmography has shown a good association between the 3 parameters for unilateral weakness. The asymmetry observed in the velocity can be predicted by a combination of frequency and duration. On the other hand, no relationship was observed between the parameters for directional preponderance. These results indicate that a clinical caloric test with frequency and duration as parameters can be used to predict the unilateral weakness, which would be obtained by use of nystagmography. We propose an evaluation of the caloric test on the basis of diagrams combining the 3 response parameters.

COLOX: a new blood-based test for colorectal cancer (CRC)screening

BACKGROUND: The objective is to develop a cost-effective, reliable and non invasive screening test able to detect early CRCs and adenomas. This is done on a nucleic acids multigene assay performed on peripheral blood mononuclear cells (PBMCs). METHODS: A colonoscopy-controlled study was conducted on 179 subjects. 92 subjects (21 CRC, 30 adenoma >1 cm and 41 controls) were used as training set to generate a signature. Other 48 subjects kept blinded (controls, CRC and polyps) were used as a test set. To determine organ and disease specificity 38 subjects were used: 24 with inflammatory bowel disease (IBD),14 with other cancers (OC). Blood samples were taken and PBMCs were purified. After the RNA extraction, multiplex RT-qPCR was applied on 92 different candidate biomarkers. After different univariate and multivariate analysis 60 biomarkers with significant p-values (<0.01) were selected. 2 distinct biomarker signatures are used to separate patients without lesion from those with CRC or with adenoma, named COLOX CRC and COLOX POL. COLOX performances were validated using random resampling method, bootstrap. RESULTS: COLOX CRC and POL tests successfully separate patients without lesions from those with CRC (Se 67%, Sp 93%, AUC 0.87), and from those with adenoma > 1cm (Se 63%, Sp 83%, AUC 0.77). 6/24 patients in the IBD group and 1/14 patients in the OC group have a positive COLOX CRC. CONCLUSION: The two COLOX tests demonstrated a high Se and Sp to detect the presence of CRCs and adenomas > 1 cm. A prospective, multicenter, pivotal study is underway in order to confirm these promising results in a larger cohort.

Functional responses and heterogeneities: an experimental test with cladocerans

The functional response of predators is usually modelled as a function of absolute prey density. Arditi and Ginzburg have suggested that it should often depend instead on the prey available per capita of predators, i.e. on the prey/predator ratio. Theory suggests that these two forms of dependence are related to the degree of spatial and temporal heterogeneity. Experiments using four filter-feeding cladoceran species were designed to test this hypothesis and to investigate the relation between individual behaviour and population dynamics. The patterns of population abundance that the cladocerans reached at equilibrium match the expectation that species with homogeneous spatial behaviour follow prey-dependent dynamics while those with heterogeneous behaviour follow ratio-dependent dynamics.

Conditional manipulation of sex ratios by ant workers: A test of kin selection theory

Variable queen mating frequencies provide a unique opportunity to study the resolution of worker-queen conflict over sex ratio in social Hymenoptera, because the conflict is maximal in colonies headed by a singly mated queen and is weak or nonexistent in colonies headed by a multiply mated queen. In the wood ant Formica exsecta, workers in colonies with a singly mated queen, but not those in colonies with a multiply mated queen, altered the sex ratio of queen-laid eggs by eliminating males to preferentially raise queens. By this conditional response to queen mating frequency, workers enhance their inclusive fitness.

What drives invasibility? A multi-model inference test and spatial modelling of alien plant species richness patterns in northern Portugal

Understanding and anticipating biological invasions can focus either on traits that favour species invasiveness or on features of the receiving communities, habitats or landscapes that promote their invasibility. Here, we address invasibility at the regional scale, testing whether some habitats and landscapes are more invasible than others by fitting models that relate alien plant species richness to various environmental predictors. We use a multi-model information-theoretic approach to assess invasibility by modelling spatial and ecological patterns of alien invasion in landscape mosaics and testing competing hypotheses of environmental factors that may control invasibility. Because invasibility may be mediated by particular characteristics of invasiveness, we classified alien species according to their C-S-R plant strategies. We illustrate this approach with a set of 86 alien species in Northern Portugal. We first focus on predictors influencing species richness and expressing invasibility and then evaluate whether distinct plant strategies respond to the same or different groups of environmental predictors. We confirmed climate as a primary determinant of alien invasions and as a primary environmental gradient determining landscape invasibility. The effects of secondary gradients were detected only when the area was sub-sampled according to predictions based on the primary gradient. Then, multiple predictor types influenced patterns of alien species richness, with some types (landscape composition, topography and fire regime) prevailing over others. Alien species richness responded most strongly to extreme land management regimes, suggesting that intermediate disturbance induces biotic resistance by favouring native species richness. Land-use intensification facilitated alien invasion, whereas conservation areas hosted few invaders, highlighting the importance of ecosystem stability in preventing invasions. Plants with different strategies exhibited different responses to environmental gradients, particularly when the variations of the primary gradient were narrowed by sub-sampling. Such differential responses of plant strategies suggest using distinct control and eradication approaches for different areas and alien plant groups.

Circadian clock-coordinated hepatic lipid metabolism: only transcriptional regulation?

By regulating the metabolism of fatty acids, carbohydrates, and xenobiotic, the mammalian circadian clock plays a fundamental role on the liver physiology. At present, it is supposed that the circadian clock regulates metabolism mostly by regulating the expression of liver enzymes at the transcriptional level. However, recent evidences suggest that some signaling pathways synchronized by the circadian clock can also influence metabolism at a post-transcriptional level. In this context, we have recently shown that the circadian clock synchronizes the rhythmic activation of the IRE1alpha pathway in the endoplasmic reticulum. The absence of circadian clock perturbs this secondary clock, provokes deregulation of endoplasmic reticulum-localized enzymes, and leads to impaired lipid metabolism. We will describe here the additional pathways synchronized by the clock and discussed the influence of the circadian clock-controlled feeding rhythm on them.

Molecular clock is involved in predictive circadian adjustment of renal function.

Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e., distal convoluted tubule (DCT) and connecting tubule (CNT) and the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf, and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, alphaENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms, and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function.