104 resultados para over-generalization and under-generalization problems


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Animals may use plant compounds to defend themselves against parasites. Wood ants, Formica paralugubris, incorporate pieces of solidified conifer resin into their nests. This behaviour inhibits the growth of bacteria and fungi in nest material and protects the ants against some detrimental microorganisms. Here, we studied the resin-collecting behaviour of ants under field and laboratory conditions. First, we focused on an important assumption of the self-medication hypothesis, which is that the animals deliberately choose the active plant material. In field cafeteria tests, the ants indeed showed a strong preference for resin over twigs and stones, which are building materials commonly encountered in their environment. We detected seasonal variation in the choice of ants: the preference for resin over twigs was more pronounced in spring than in summer, whereas in autumn the ants collected twigs and resin at equal rates. Second, we found almost similar seasonal patterns when comparing the collecting rates of pieces of wood that had been impregnated with turpentine (a distillate of oleoresin) and untreated pieces of wood, which reveals that the preference for resin is based on odour cues. Third, we tested whether the collection of resin is prophylactic or therapeutic. We found that the relative collection rate of resin versus stones did not depend on an experimental infection with the entomopathogenic fungus Metarhizium anisopliae in laboratory colonies. Together, these results show that the ants deliberately choose the resin and suggest that resin collection is prophylactic rather than therapeutic.

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The human protozoan parasite Leishmania major has been shown to exhibit several morphological and biochemical features characteristic of a cell death program when differentiating into infectious stages and under a variety of stress conditions. Although some caspase-like peptidase activity has been reported in dying parasites, no caspase gene is present in the genome. However, a single metacaspase gene is present in L. major whose encoded protein harbors the predicted secondary structure and the catalytic dyad histidine/cysteine described for caspases and other metacaspases identified in plants and yeast. The Saccharomyces cerevisiae metacaspase YCA1 has been implicated in the death of aging cells, cells defective in some biological functions, and cells exposed to different environmental stresses. In this study, we describe the functional heterologous complementation of a S. cerevisiae yca1 null mutant with the L. major metacaspase (LmjMCA) in cell death induced by oxidative stress. We show that LmjMCA is involved in yeast cell death, similar to YCA1, and that this function depends on its catalytic activity. LmjMCA was found to be auto-processed as occurs for caspases, however LmjMCA did not exhibit any activity with caspase substrates. In contrast and similarly to Arabidopsis thaliana metacaspases, LmjMCA was active towards substrates with arginine in the P1 position, with the activity being abolished following H147A and C202A catalytic site mutations. These results suggest that metacaspases are members of a family of peptidases with a role in cell death conserved in evolution notwithstanding possible differences in their catalytic activity.

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Granitic and mafic magma pulses were sequentially accreted in the spectacularly exposed shallow crustal Torres del Paine laccolith, in southern Patagonia. This 12.5 Ma pluton forms a composite intrusion with a subvertical feeding system in the west and a laccolith in the east. A key unknown in the formation of sill complexes is how individual magma pulses are assembled over time and the geometry and localization of their feeding system. High resolution zircon CA-ID-TIMS U-Pb dating shows that the laccolith grew first by under-accretion of granitic sills over 90 +/- 30 ka, linked to a `sheet-like' feeding system, followed by underplating of mafic sills after similar to 20 ka of quiescence. In the mafic sills complex, individual sills were injected by over-accretion during 41 +/- 11 ka. Our data show that successive granitic and mafic magmas emplacement generated a volume of similar to 88 km(3) in 162 +/- 11 ka. (C) 2012 Elsevier B.V. All rights reserved.

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Nephrolithiasis still remains a too frequent - and under-appreciated - cause of end-stage renal disease (ESRD), and this is all the most unfortunate since such an untoward course is now preventable in most cases. Among 1391 patients who started maintenance dialysis at Necker hospital between 1989 and 2000, nephrolithiasis was identified as the cause of ESRD in 45 of them, an overall prevalence of 3.2%. Infection stones accounted for 42.2% of cases, calcium stones for 26.7%, uric acid stones for 17.8% and hereditary diseases for 13.3%. The proportion of nephrolithiasis-associated ESRD declined from 4.7% to 2.2% from the 1989-1991 to the 1998-2000 period, as a result of the decreased incidence of ESRD in patients with infection and calcium nephrolithiasis. Based on our observations and on published reports, it emerges that most cases of nephrolithiasis-associated ESRD were due to sub-optimal management (especially in the case of infection or cystine stones) or to late (or erroneous) etiologic diagnosis, precluding early institution of appropriate therapeutic measures. In particular, several patients with primary hyperoxaluria or 2,8-dihydroxyadeninuria were diagnosed while already on dialysis or after unsuccessful kidney transplantation, due to wrong initial diagnosis. In conclusion, thanks to recent advances in diagnosis and management of stone formers, ESRD should now be prevented in the great majority of patients, at the condition of early etiologic diagnosis based on accurate morphoconstitutional analysis of calculi and metabolic evaluation, and early implementation of appropriate preventive medical treatment.

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Divergence of protein sequences and gene expression patterns are two fundamental mechanisms that generate organismal diversity. Here, we have used genome and transcriptome data from eight mammals and one bird to study the positive correlation of these two processes throughout mammalian evolution. We demonstrate that the correlation is stable over time and most pronounced in neural tissues, which indicates that it is the result of strong negative selection. The correlation is not driven by genes with specific functions and may instead best be viewed as an evolutionary default state, which can nevertheless be evaded by certain gene types. In particular, genes with developmental and neural functions are skewed toward changes in gene expression, consistent with selection against pleiotropic effects associated with changes in protein sequences. Surprisingly, we find that the correlation between expression divergence and protein divergence is not explained by between-gene variation in expression level, tissue specificity, protein connectivity, or other investigated gene characteristics, suggesting that it arises independently of these gene traits. The selective constraints on protein sequences and gene expression patterns also fluctuate in a coordinate manner across phylogenetic branches: We find that gene-specific changes in the rate of protein evolution in a specific mammalian lineage tend to be accompanied by similar changes in the rate of expression evolution. Taken together, our findings highlight many new aspects of the correlation between protein divergence and expression divergence, and attest to its role as a fundamental property of mammalian genome evolution.

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BACKGROUND: Treatment strategies for acute basilar artery occlusion (BAO) are based on case series and data that have been extrapolated from stroke intervention trials in other cerebrovascular territories, and information on the efficacy of different treatments in unselected patients with BAO is scarce. We therefore assessed outcomes and differences in treatment response after BAO. METHODS: The Basilar Artery International Cooperation Study (BASICS) is a prospective, observational registry of consecutive patients who presented with an acute symptomatic and radiologically confirmed BAO between November 1, 2002, and October 1, 2007. Stroke severity at time of treatment was dichotomised as severe (coma, locked-in state, or tetraplegia) or mild to moderate (any deficit that was less than severe). Outcome was assessed at 1 month. Poor outcome was defined as a modified Rankin scale score of 4 or 5, or death. Patients were divided into three groups according to the treatment they received: antithrombotic treatment only (AT), which comprised antiplatelet drugs or systemic anticoagulation; primary intravenous thrombolysis (IVT), including subsequent intra-arterial thrombolysis; or intra-arterial therapy (IAT), which comprised thrombolysis, mechanical thrombectomy, stenting, or a combination of these approaches. Risk ratios (RR) for treatment effects were adjusted for age, the severity of neurological deficits at the time of treatment, time to treatment, prodromal minor stroke, location of the occlusion, and diabetes. FINDINGS: 619 patients were entered in the registry. 27 patients were excluded from the analyses because they did not receive AT, IVT, or IAT, and all had a poor outcome. Of the 592 patients who were analysed, 183 were treated with only AT, 121 with IVT, and 288 with IAT. Overall, 402 (68%) of the analysed patients had a poor outcome. No statistically significant superiority was found for any treatment strategy. Compared with outcome after AT, patients with a mild-to-moderate deficit (n=245) had about the same risk of poor outcome after IVT (adjusted RR 0.94, 95% CI 0.60-1.45) or after IAT (adjusted RR 1.29, 0.97-1.72) but had a worse outcome after IAT compared with IVT (adjusted RR 1.49, 1.00-2.23). Compared with AT, patients with a severe deficit (n=347) had a lower risk of poor outcome after IVT (adjusted RR 0.88, 0.76-1.01) or IAT (adjusted RR 0.94, 0.86-1.02), whereas outcomes were similar after treatment with IAT or IVT (adjusted RR 1.06, 0.91-1.22). INTERPRETATION: Most patients in the BASICS registry received IAT. Our results do not support unequivocal superiority of IAT over IVT, and the efficacy of IAT versus IVT in patients with an acute BAO needs to be assessed in a randomised controlled trial. FUNDING: Department of Neurology, University Medical Center Utrecht.

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Non-medical use of prescription drugs (NMUPD) is increasing among the general population, particularly among teenagers and young adults. Although prescription drugs are considered safer than illicit street drugs, NMUPD can lead to detrimental consequences. The aim of the present study was to investigate the relationship between drug use (NMUPD on the one side, illicit street drugs on the other side) with mental health issues and then compare these associations. A representative sample of 5719 young Swiss men aged around 20 years filled in a questionnaire as part of the ongoing baseline Cohort Study on Substance Use Risk Factors (C-SURF). Drug use (16 illicit street drugs and 5 NMUPDs, including sleeping pills, sedatives, pain killers, antidepressants, stimulants) and mental health issues (depression, SF12) were assessed. Simple and multiple linear regressions were employed. In simple regressions, all illicit and prescription drugs were associated with poorer mental health. In multiple regressions, most of the NMUPDs, except for stimulants, were significantly associated with poorer mental health and with depression. On the contrary, the only associations that remained significant between illicit street drugs and mental health involved cannabis. NMUPD is of growing concern not only because of its increasing occurrence, but also because of its association with depression and mental health problems, which is stronger than the association observed between these problems and illicit street drug use, excepted for cannabis. Therefore, NMUPD must be considered in screening for substance use prevention purposes.

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The amount of sequence data available today highly facilitates the access to genes from many gene families. Primers amplifying the desired genes over a range of species are readily obtained by aligning conserved gene regions, and laborious gene isolation procedures can often be replaced by quicker PCR-based approaches. However, in the case of multigene families, PCR-based approaches bear the often ignored risk of incomplete isolation of family members. This problem is most prominent in gene families with highly variable and thus unpredictable number of gene copies among species, such as in the major histocompatibility complex (MHC). In this study, we (i) report new primers for the isolation of the MHC class IIB (MHCIIB) gene family in birds and (ii) share our experience with isolating MHCIIB genes from an unprecedented number of avian species from all over the avian phylogeny. We report important and usually underappreciated problems encountered during PCR-based multigene family isolation and provide a collection of measures to help significantly improving the chance of successfully isolating complete multigene families using PCR-based approaches.

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Deduction allows us to draw consequences from previous knowledge. Deductive reasoning can be applied to several types of problem, for example, conditional, syllogistic, and relational. It has been assumed that the same cognitive operations underlie solutions to them all; however, this hypothesis remains to be tested empirically. We used event-related fMRI, in the same group of subjects, to compare reasoning-related activity associated with conditional and syllogistic deductive problems. Furthermore, we assessed reasoning-related activity for the two main stages of deduction, namely encoding of premises and their integration. Encoding syllogistic premises for reasoning was associated with activation of BA 44/45 more than encoding them for literal recall. During integration, left fronto-lateral cortex (BA 44/45, 6) and basal ganglia activated with both conditional and syllogistic reasoning. Besides that, integration of syllogistic problems additionally was associated with activation of left parietal (BA 7) and left ventro-lateral frontal cortex (BA 47). This difference suggests a dissociation between conditional and syllogistic reasoning at the integration stage. Our finding indicates that the integration of conditional and syllogistic reasoning is carried out by means of different, but partly overlapping, sets of anatomical regions and by inference, cognitive processes. The involvement of BA 44/45 during both encoding (syllogisms) and premise integration (syllogisms and conditionals) suggests a central role in deductive reasoning for syntactic manipulations and formal/linguistic representations.

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Size-selective fishing, environmental changes and reproductive strategies are expected to affect life-history traits such as the individual growth rate. The relative contribution of these factors is not clear, particularly whether size-selective fishing can have a substantial impact on the genetics and hence on the evolution of individual growth rates in wild populations. We analysed a 25-year monitoring survey of an isolated population of the Alpine whitefish Coregonus palaea. We determined the selection differentials on growth rate, the actual change of growth rate over time and indicators of reproductive strategies that may potentially change over time. The selection differential can be reliably estimated in our study population because almost all the fish are harvested within their first years of life, i.e. few fish escape fishing mortality. We found a marked decline in average adult growth rate over the 25 years and a significant selection differential for adult growth, but no evidence for any linear change in reproductive strategies over time. Assuming that the heritability of growth in this whitefish corresponds to what was found in other salmonids, about a third of the observed decline in growth rate would be linked to fishery-induced evolution. Size-selective fishing seems to affect substantially the genetics of individual growth in our study population.

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The use of bone mineral density (BMD) for fracture discrimination may be improved by considering bone microarchitecture. Texture parameters such as trabecular bone score (TBS) or mean Hurst parameter (H) could help to find women who are at high risk of fracture in the non-osteoporotic group. The purpose of this study was to combine BMD and microarchitectural texture parameters (spine TBS and calcaneus H) for the detection of osteoporotic fractures. Two hundred and fifty five women had a lumbar spine (LS), total hip (TH), and femoral neck (FN) DXA. Additionally, texture analyses were performed with TBS on spine DXA and with H on calcaneus radiographs. Seventy-nine women had prevalent fragility fractures. The association with fracture was evaluated by multivariate logistic regressions. The diagnostic value of each parameter alone and together was evaluated by odds ratios (OR). The area under curve (AUC) of the receiver operating characteristics (ROC) were assessed in models including BMD, H, and TBS. Women were also classified above and under the lowest tertile of H or TBS according to their BMD status. Women with prevalent fracture were older and had lower TBS, H, LS-BMD, and TH-BMD than women without fracture. Age-adjusted ORs were 1.66, 1.70, and 1.93 for LS, FN, and TH-BMD, respectively. Both TBS and H remained significantly associated with fracture after adjustment for age and TH-BMD: OR 2.07 [1.43; 3.05] and 1.47 [1.04; 2.11], respectively. The addition of texture parameters in the multivariate models didn't show a significant improvement of the ROC-AUC. However, women with normal or osteopenic BMD in the lowest range of TBS or H had significantly more fractures than women above the TBS or the H threshold. We have shown the potential interest of texture parameters such as TBS and H in addition to BMD to discriminate patients with or without osteoporotic fractures. However, their clinical added values should be evaluated relative to other risk factors.

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Clients' personality traits and individual characteristics, such as age, gender, reason for seeking counselling, and further compounding problems in their personal or academic lives, may pose risk factors that render career decision making difficult and may also impact the overall effectiveness of a career counselling intervention. Neuroticism and conscien- tiousness as well as clients' age and gender directly affected clients' satisfaction with life and certain aspects of their career indecision scores before participating in our short-term career counselling intervention. Career counsellors can use personality and career-specific and career-non-specific instruments to tailor career counselling interventions to meet clients' individual needs.

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DNA that survives in museum specimens, bones and other tissues recovered by archaeologists is invariably fragmented and chemically modified. The extent to which such modifications accumulate over time is largely unknown but could potentially be used to differentiate between endogenous old DNA and present-day DNA contaminating specimens and experiments. Here we examine mitochondrial DNA sequences from tissue remains that vary in age between 18 and 60,000 years with respect to three molecular features: fragment length, base composition at strand breaks, and apparent C to T substitutions. We find that fragment length does not decrease consistently over time and that strand breaks occur preferentially before purine residues by what may be at least two different molecular mechanisms that are not yet understood. In contrast, the frequency of apparent C to T substitutions towards the 5'-ends of molecules tends to increase over time. These nucleotide misincorporations are thus a useful tool to distinguish recent from ancient DNA sources in specimens that have not been subjected to unusual or harsh treatments.

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OBJECTIVES: (1) To evaluate the changes in surface roughness and gloss after simulated toothbrushing of 9 composite materials and 2 ceramic materials in relation to brushing time and load in vitro; (2) to assess the relationship between surface gloss and surface roughness. METHODS: Eight flat specimens of composite materials (microfilled: Adoro, Filtek Supreme, Heliomolar; microhybrid: Four Seasons, Tetric EvoCeram; hybrid: Compoglass F, Targis, Tetric Ceram; macrohybrid: Grandio), two ceramic materials (IPS d.SIGN and IPS Empress polished) were fabricated according to the manufacturer's instructions and optimally polished with up to 4000 grit SiC. The specimens were subjected to a toothbrushing (TB) simulation device (Willytec) with rotating movements, toothpaste slurry and at three different loads (100g/250g/350g). At hourly intervals from 1h to 10h TB, mean surface roughness Ra was measured with an optical sensor and the surface gloss (Gl) with a glossmeter. Statistical analysis was performed for log-transformed Ra data applying two-way ANOVA to evaluate the interaction between load and material and load and brushing time. RESULTS: There was a significant interaction between material and load as well as between load and brushing time (p<0.0001). The microhybrid and hybrid materials demonstrated more surface deterioration with higher loads, whereas with the microfilled resins Heliomolar and Adoro it was vice versa. For ceramic materials, no or little deterioration was observed over time and independent of the load. The ceramic materials and 3 of the composite materials (roughness) showed no further deterioration after 5h of toothbrushing. Mean surface gloss was the parameter which discriminated best between the materials, followed by mean surface roughness Ra. There was a strong correlation between surface gloss and surface roughness for all the materials except the ceramics. The evaluation of the deterioration curves of individual specimens revealed a more or less synchronous course suspecting hinting specific external conditions and not showing the true variability in relation to the tested material. SIGNIFICANCE: The surface roughness and gloss of dental materials changes with brushing time and load and thus results in different material rankings. Apart from Grandio, the hybrid composite resins were more prone to surface changes than microfilled composites. The deterioration potential of a composite material can be quickly assessed by measuring surface gloss. For this purpose, a brushing time of 10h (=72,000 strokes) is needed. In further comparative studies, specimens of different materials should be tested in one series to estimate the true variability.

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Differences in physico-chemical characteristics of bone grafts to fill bone defects have been demonstrated to influence in vitro bacterial biofilm formation. Aim of the study was to investigate in vivo staphylococcal biofilm formation on different calcium phosphate bone substitutes. A foreign-body guinea-pig infection model was used. Teflon cages prefilled with β-tricalcium phosphate, calcium-deficient hydroxyapatite, or dicalcium phosphate (DCP) scaffold were implanted subcutaneously. Scaffolds were infected with 2 × 10(3) colony-forming unit of Staphylococcus aureus (two strains) or S. epidermidis and explanted after 3, 24 or 72 h of biofilm formation. Quantitative and qualitative biofilm analysis was performed by sonication followed by viable counts, and microcalorimetry, respectively. Independently of the material, S. aureus formed increasing amounts of biofilm on the surface of all scaffolds over time as determined by both methods. For S. epidermidis, the biofilm amount decreased over time, and no biofilm was detected by microcalorimetry on the DCP scaffolds after 72 h of infection. However, when using a higher S. epidermidis inoculum, increasing amounts of biofilm were formed on all scaffolds as determined by microcalorimetry. No significant variation in staphylococcal in vivo biofilm formation was observed between the different materials tested. This study highlights the importance of in vivo studies, in addition to in vitro studies, when investigating biofilm formation of bone grafts.