247 resultados para acetyl group specificity
Resumo:
Intraspecific coalitional aggression between groups of individuals is a widespread trait in the animal world. It occurs in invertebrates and vertebrates, and is prevalent in humans. What are the conditions under which coalitional aggression evolves in natural populations? In this article, I develop a mathematical model delineating conditions where natural selection can favor the coevolution of belligerence and bravery between small-scale societies. Belligerence increases an actor's group probability of trying to conquer another group and bravery increase the actors's group probability of defeating an attacked group. The model takes into account two different types of demographic scenarios that may lead to the coevolution of belligerence and bravery. Under the first, the fitness benefits driving the coevolution of belligerence and bravery come through the repopulation of defeated groups by fission of victorious ones. Under the second demographic scenario, the fitness benefits come through a temporary increase in the local carrying capacity of victorious groups, after transfer of resources from defeated groups to victorious ones. The analysis of the model suggests that the selective pressures on belligerence and bravery are stronger when defeated groups can be repopulated by victorious ones. The analysis also suggests that, depending on the shape of the contest success function, costly bravery can evolve in groups of any size.
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The aim of this study was to determine the impact of the learning curve on the diagnostic performances of CT colonography. Two blinded teams, each having a radiologist and gastroenterologist, prospectively examined 50 patients using helical CT scan followed by colonoscopy. Intermediate data evaluation was performed after 24 data sets (group 1) and compared with data from 26 subsequent patients (group 2). Parameters evaluated included sensitivity, specificity, false-positive and false-negative findings, time of data acquisition and interpretation. Using colonoscopy as the gold standard, sensitivity for CT colonography was for lesions >5 mm 63% for both teams for group 1 patients; for group 2 patients sensitivity was 45% for team 1 and 64% for team 2. Specificity per patients was for patient group 1 42% for team 1 and 58% for team 2; for patient group 2 it was 79% for both teams ( p=0.04 for team 1; p=0.2 for team 2). Comparing group 1 with group 2, the number of false-positive findings decreased significantly ( p=0.02). Furthermore, the mean time of data evaluation decreased from 45 to 17 min ( p=0.002) and the mean time of data acquisition from 19 to 17 min. With increasing experience, specificity and the time required for data interpretation improved and false positives decreased. There was no significant change of sensitivity, false-negative findings and time of data acquisition. A minimum experience of the readers is required for data interpretation of CT colonography.
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Effective empirical treatment is of paramount importance to improve the outcome of patients with Staphylococcus aureus bacteraemia. We aimed to evaluate a PCR-based rapid diagnosis of methicillin resistance (GeneXpert MRSA) after early detection of S. aureus bacteraemia using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Patients with a first episode of S. aureus bacteraemia identified using MALDI-TOF MS were randomized in a prospective interventional open study between October 2010 and August 2012. In the control group, antibiotic susceptibility testing was performed after MALDI-TOF MS identification on blood culture pellets. In the intervention group, a GeneXpert MRSA was performed after S. aureus identification. The primary outcome was the performance of GeneXpert MRSA directly on blood cultures. We then assessed the impact of early diagnosis of methicillin resistance on the empirical treatment. In all, 197 episodes of S. aureus bacteraemia were included in the study, of which 106 were included in the intervention group. Median time from MALDI-TOF MS identification to GeneXpert MRSA result was 97 min (range 25-250). Detection of methicillin resistance using GeneXpert MRSA had a sensitivity of 99% and a specificity of 100%. There was less unnecessary coverage of MRSA in the intervention group (17.1% versus 29.2%, p 0.09). GeneXpert MRSA was highly reliable in diagnosing methicillin resistance when performed directly on positive blood cultures. This could help to avoid unnecessary prescriptions of anti-MRSA agents and promote the introduction of earlier adequate coverage in unsuspected cases.
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There are no validated criteria for the diagnosis of sensory neuronopathy (SNN) yet. In a preliminary monocenter study a set of criteria relying on clinical and electrophysiological data showed good sensitivity and specificity for a diagnosis of probable SNN. The aim of this study was to test these criteria on a French multicenter study. 210 patients with sensory neuropathies from 15 francophone reference centers for neuromuscular diseases were included in the study with an expert diagnosis of non-SNN, SNN or suspected SNN according to the investigations performed in these centers. Diagnosis was obtained independently from the set of criteria to be tested. The expert diagnosis was taken as the reference against which the proposed SNN criteria were tested. The set relied on clinical and electrophysiological data easily obtainable with routine investigations. 9/61 (16.4 %) of non-SNN patients, 23/36 (63.9 %) of suspected SNN, and 102/113 (90.3 %) of SNN patients according to the expert diagnosis were classified as SNN by the criteria. The SNN criteria tested against the expert diagnosis in the SNN and non-SNN groups had 90.3 % (102/113) sensitivity, 85.2 % (52/61) specificity, 91.9 % (102/111) positive predictive value, and 82.5 % (52/63) negative predictive value. Discordance between the expert diagnosis and the SNN criteria occurred in 20 cases. After analysis of these cases, 11 could be reallocated to a correct diagnosis in accordance with the SNN criteria. The proposed criteria may be useful for the diagnosis of probable SNN in patients with sensory neuropathy. They can be reached with simple clinical and paraclinical investigations.
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This study evaluated the prenatal diagnosis of Turner syndrome by ultrasound examination in an unselected population from all over Europe. Data from 19 congenital malformation registries from 11 European countries were analyzed. Turner syndrome was diagnosed in 125 cases (7.2%) in a total of 1,738 chromosome abnormalities. Sixty-seven percent of cases were detected prenatally by ultrasound examination due to the presence of congenital defects. The most frequent anomalies were cystic hygroma (59.5%) and hydrops fetalis (19%). The most frequent karyotype was 45,X (81.6%) followed by different types of mosaicism (16.8%). Significant differences in congenital defects (P = 0.0003) were observed between 45,X karyotypes and 45,X mosaicism cases. Prenatal counseling for 45,X mosaicism should take into account the expectation of a milder phenotype. In 78.6% of cases diagnosed by ultrasound examination due to congenital anomalies, the pregnancy was terminated. Prenatal detection of Turner syndrome by ultrasound examination was high in this unselected population.
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This study examined the validity and reliability of a sequential "Run-Bike-Run" test (RBR) in age-group triathletes. Eight Olympic distance (OD) specialists (age 30.0 ± 2.0 years, mass 75.6 ± 1.6 kg, run VO2max 63.8 ± 1.9 ml· kg(-1)· min(-1), cycle VO2peak 56.7 ± 5.1 ml· kg(-1)· min(-1)) performed four trials over 10 days. Trial 1 (TRVO2max) was an incremental treadmill running test. Trials 2 and 3 (RBR1 and RBR2) involved: 1) a 7-min run at 15 km· h(-1) (R1) plus a 1-min transition to 2) cycling to fatigue (2 W· kg(-1) body mass then 30 W each 3 min); 3) 10-min cycling at 3 W· kg(-1) (Bsubmax); another 1-min transition and 4) a second 7-min run at 15 km· h(-1) (R2). Trial 4 (TT) was a 30-min cycle - 20-min run time trial. No significant differences in absolute oxygen uptake (VO2), heart rate (HR), or blood lactate concentration ([BLA]) were evidenced between RBR1 and RBR2. For all measured physiological variables, the limits of agreement were similar, and the mean differences were physiologically unimportant, between trials. Low levels of test-retest error (i.e. ICC <0.8, CV<10%) were observed for most (logged) measurements. However [BLA] post R1 (ICC 0.87, CV 25.1%), [BLA] post Bsubmax (ICC 0.99, CV 16.31) and [BLA] post R2 (ICC 0.51, CV 22.9%) were least reliable. These error ranges may help coaches detect real changes in training status over time. Moreover, RBR test variables can be used to predict discipline specific and overall TT performance. Cycle VO2peak, cycle peak power output, and the change between R1 and R2 (deltaR1R2) in [BLA] were most highly related to overall TT distance (r = 0.89, p < 0. 01; r = 0.94, p < 0.02; r = 0.86, p < 0.05, respectively). The percentage of TR VO2max at 15 km· h(-1), and deltaR1R2 HR, were also related to run TT distance (r = -0.83 and 0.86, both p < 0.05).
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Metabolic problems lead to numerous failures during clinical trials, and much effort is now devoted to developing in silico models predicting metabolic stability and metabolites. Such models are well known for cytochromes P450 and some transferases, whereas less has been done to predict the activity of human hydrolases. The present study was undertaken to develop a computational approach able to predict the hydrolysis of novel esters by human carboxylesterase hCES2. The study involved first a homology modeling of the hCES2 protein based on the model of hCES1 since the two proteins share a high degree of homology (congruent with 73%). A set of 40 known substrates of hCES2 was taken from the literature; the ligands were docked in both their neutral and ionized forms using GriDock, a parallel tool based on the AutoDock4.0 engine which can perform efficient and easy virtual screening analyses of large molecular databases exploiting multi-core architectures. Useful statistical models (e.g., r (2) = 0.91 for substrates in their unprotonated state) were calculated by correlating experimental pK(m) values with distance between the carbon atom of the substrate's ester group and the hydroxy function of Ser228. Additional parameters in the equations accounted for hydrophobic and electrostatic interactions between substrates and contributing residues. The negatively charged residues in the hCES2 cavity explained the preference of the enzyme for neutral substrates and, more generally, suggested that ligands which interact too strongly by ionic bonds (e.g., ACE inhibitors) cannot be good CES2 substrates because they are trapped in the cavity in unproductive modes and behave as inhibitors. The effects of protonation on substrate recognition and the contrasting behavior of substrates and products were finally investigated by MD simulations of some CES2 complexes.
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PURPOSE: To evaluate the diagnostic value of previously described MR features used for detecting suspected placental invasion according to observers' experience. MATERIALS AND METHODS: Our population included 25 pregnant women (mean age 35.16) investigated by prenatal MRI (1.5T, T1- and T2-weighted MR-sequences without i.v. contrast), among them 12 with histopathologically proven placental invasion and 13 women (52%) without placental invasion used as control group. Two senior and two junior radiologists blindly and independently reviewed MR-examinations in view of 6 previously defined MR-features indicating presence and degree of placental invasion (placenta increta, accreta or percreta). For each reader the sensibility, specificity, and receiver operating curve (ROC) were calculated. Interobserver agreements between senior and junior readers were determined. Stepwise logistic regression was performed including the 6 MR-features predictive of placental invasion. RESULTS: Demographics between both groups were statistically equivalent. Overall sensitivity and specificity for placental invasion was 90.9% and 75.0% for seniors and 81.8% and 61.8% for juniors, respectively. The best single MR-feature indicating placental invasion was T2-hypointense placental bands (r(2)=0.28), followed by focally interrupted myometrial border, infiltration of pelvic organs and tenting of the bladder (r(2)=0.36). Interobserver agreement for detecting placental invasion was 0.64 for seniors and 0.41 for juniors, thus substantial and moderate, respectively. Seniors detected placental invasion and depth of infiltration with significantly higher diagnostic certitude than juniors (p=0.0002 and p=0.0282, respectively). CONCLUSION: MRI can be a reliable and reproducible tool for the detection of suspected placental invasion, but the diagnostic value significantly depends on observers' experience.
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Pathogens represent a threat to all organisms, which generates a coevolutionary arms race. Social insects provide an interesting system to study host-pathogen interactions, because their defences depend on both the individual and collective responses, and involve genetic, physiological, behavioral and organizational mechanisms. In this thesis, I studied the evolutionary ecology of the resistance of ant queens and workers to natural fungal pathogens. Mechanisms that increase within-colony genetic diversity, like polyandry and polygyny, decrease relatedness among colony mates, which reduces the strength of selection for the evolution and maintenance of altruistic behavior. A leading hypothesis posits that intracolonial genetic diversity is adaptive because it reduces the risk of pathogen transmission. In chapter 1, I examine individual resistance in ant workers of Formica selysi, a species that shows natural variation in colony queen number. I discuss how this variation might be beneficial to resist natural fungal pathogens in groups. Overall my results indicate that there is genetic variation for fungal resistance in workers, a requirement for the 'genetic diversity for pathogen resistance' hypothesis. However I was not able to detect direct evidence that group diversity improves the survival of focal ants or reduces pathogen transmission. Thus, although the coexistence of multiple queens increases the within-colony variance in worker resistance, it remains unclear whether it protects ant colonies from pathogens and whether it is comparable to polyandry in other social insects. Traditionally, it was thought that the immune system of invertebrates lacked memory and specificity. In chapter 2, I investigate individual immunity in ant queens and show that they may be able to adjust their pathogen defences in response to their current environment by means of immune priming, which bears similarities with the adaptive immunity of vertebrates. However, my results indicate that the expression of immune priming in ant queens may be influenced by factors like mating status, mating conditions or host species. In addition, I showed that mating increases pathogen resistance in çhe two ant species that I studied (F. selysi and Lasius niger). This raises the question of how ant queens invest heavily in both maintenance and reproduction, which I discuss in the context of the evolution of social organization. In chapter 3,1 investigate if transgenerational priming against a fungal pathogen protects the queen progeny. I failed to detect this effect, and discuss why the detection of transgenerational immune priming in ants is a difficult task. Overall, this thesis illustrates some of the individual and collective mechanisms that likely played a role in allowing ants to become one of the most diverse and ecologically successful groups of organisms. -- Les pathogènes représentent une menace pour tous les organismes, ce qui a engendré l'évolution d'une course aux armements. Les insectes sociaux sont un système intéressant permettant d'étudier les interactions hôtes-pathogènes, car leurs défenses dépendent de réponses aussi bien individuelles que collectives, et impliquent des mécanismes génétiques, physiologiques, comportementaux et organisationnels. Dans cette thèse, j'ai étudié l'écologie évolutive de la résistance des reines et des ouvrières de fourmis exposées à des champignons pathogènes. Les facteurs augmentant la diversité génétique à l'intérieur de la colonie, comme la polyandrie et la polygynie, diminuent la parenté, ce qui réduit la pression de sélection pour l'évolution et la maintenance des comportements altruistes. Une hypothèse dominante stipule que la diversité génétique à l'intérieur de la colonie est adaptative car elle réduit le risque de transmission des pathogènes. Dans le chapitre 1, nous examinons la résistance individuelle à des pathogènes fongiques chez les ouvrières de Formica selysi, une espèce présentant une variation naturelle dans le nombre de reines par colonie. Nous discutons aussi de la possibilité que ces variations individuelles augmentent la capacité du groupe à résister à des champignons pathogènes. Dans l'ensemble, nos résultats indiquent une variation génétique dans la résistance aux champignons chez les ouvrières, un prérequis à l'hypothèse que la diversité génétique du groupe augmente la résistance aux pathogènes. Cependant, nous n'avons pas pu détecter une preuve directe que la diversité du groupe augmente la survie de fourmis focales ou réduise la transmission des pathogènes. Ainsi, bien que la coexistence de plusieurs reines augmente la variance dans la résistance des ouvrières à l'intérieur de la colonie, la question de savoir si cela protège les colonies de fourmis contre les pathogènes et si cela est comparable à la polyandrie chez d'autres insectes sociaux reste ouverte. Traditionnellement, il était admis que le système immunitaire des invertébrés ne possédait pas de mémoire et était non-spécifique. Dans le chapitre 2, nous avons étudié l'immunité individuelle chez des reines de fourmis. Nous avons montré que les reines pourraient être capables d'ajuster leurs défenses contre les pathogènes en réponse à leur environnement, grâce à une pré-activation du système immunitaire (« immune priming ») ressemblant à l'immunité adaptative des vertébrés. Cependant, nos résultats indiquent que cette pré-activation du système immunitaire chez les reines dépend du fait d'être accouplée ou non, des conditions d'accouplement, ou de l'espèce. De plus, nous avons montré que l'accouplement augmente la résistance aux pathogènes chez les deux espèces que nous avons étudié (F. selysi et Lasius niger). Ceci pose la question de la capacité des reines à investir fortement aussi bien dans la maintenance que dans la reproduction, ce que nous discutons dans le contexte de l'évolution de l'organisation sociale. Dans le chapitre 3, nous étudions si la pré-activation trans-générationelle du système immunitaire [« trans-generational immune priming ») protège la progéniture de la reine contre un champignon pathogène. Nous n'avons par réussi à détecter cet effet, et discutons des raisons pour lesquelles la détection de la pré-activation trans-générationelle du système immunitaire chez les fourmis est une tâche difficile. Dans l'ensemble, cette thèse illustre quelques-uns des mécanismes individuels et collectifs qui ont probablement contribué à la diversité et à l'important succès écologique des fourmis.
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In the Ballabeina study, we investigated age- and BMI-group-related differences in aerobic fitness (20 m shuttle run), agility (obstacle course), dynamic (balance beam) and static balance (balance platform), and physical activity (PA, accelerometers) in 613 children (M age = 5.1 years, SD = 0.6). Normal weight (NW) children performed better than overweight (OW) children in aerobic fitness, agility, and dynamic balance (all p <.001), while OWchildren had a better static balance (p < .001). BMI-group-related differences in aerobic fitness and agility were larger in older children (p for interaction with age = .01) in favor of the NW children. PA did not differ between NW and OW (p > or = .1), but did differ between NW and obese children (p < .05). BMI-group-related differences in physical fitness can already be present in preschool-age children.
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We evaluated whether preeclampsia is associated with elevated circulating levels of High mobility group box 1 protein (HMGB-1), a nuclear protein with proinflammatory effects when released extracellularly. We enrolled 48 women, 32 in third trimester pregnancy (16 with, 16 without preeclampsia), and 16 healthy non pregnant. In the peripheral blood of pregnant women, HMGB-1 concentration was assessed serially, before and after delivery. With or without preeclampsia, third trimester pregnancy was associated with elevated levels of HMGB-1. This elevation is exaggerated in preeclampsia. The source of HMGB-1 observed in these conditions is likely to involve tissues other than the placenta itself.
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BACKGROUND AND AIMS: Ficolin-2 is an acute phase reactant produced by the liver and targeted to recognize N-acetyl-glucosamine which is present in bacterial and fungal cell walls. We recently showed that ficolin-2 serum levels were significantly higher in CD patients compared to healthy controls. We aimed to evaluate serum ficolin-2 concentrations in CD patients regarding their correlation with endoscopic severity and to compare them with clinical activity, fecal calprotectin, and CRP. METHODS: Patients provided fecal and blood samples before undergoing ileo-colonoscopy. Disease activity was scored clinically according to the Harvey-Bradshaw Index (HBI) and endoscopically according to the simplified endoscopic score for CD (SES-CD). Ficolin-2 serum levels and fecal calprotectin levels were measured by ELISA. RESULTS: A total of 136 CD patients were prospectively included (mean age at inclusion 41.5±15.4 years, 37.5% females). Median HBI was 3 [2-6] points, median SES-CD was 5 [2-8], median fecal calprotectin was 301 [120-703] μg/g, and median serum ficolin-2 was 2.69 [2.02-3.83] μg/mL. SES-CD correlated significantly with calprotectin (R=0.676, P<0.001), CRP (R=0.458, P<0.001), HBI (R=0.385, P<0.001), and serum ficolin-2 levels (R=0.171, P=0.047). Ficolin-2 levels were higher in CD patients with mild endoscopic disease compared to patients in endoscopic remission (P=0.015) but no difference was found between patients with mild, moderate, and severe endoscopic disease. CONCLUSIONS: Ficolin-2 serum levels correlate worse with endoscopic CD activity when compared to fecal calprotectin or CRP.