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[Assessment of the nutritional state of a 10-14 year-old adolescent population in primary care. Evolution study (1994-2000)].

OBJECTIVE: To analyse the evolution over the last six years of the nutritional state of the current adolescent population (10-14 years old) of our health area in order to identify risk groups and to draw up specific therapeutic strategies. DESIGN: Observational, retrospective and longitudinal study. Systematic and stratified sampling. SETTING: Rural primary care. PATIENTS: Sample of 360 healthy adolescents, aged between 10 and 14 (176 boys and 184 girls) out of a sample frame of 811. Interventions. During the 1999-2000 school year (year 2000), weight, height, Quetelet index (QI) and Body Mass Index (BMI) of one in every three young people at their routine health check-up were recorded. Those with acute and/or chronic pathology that might affect their nutritional state or with dietary restrictions of any sort were excluded. The weight, height, QI and BMI of the check-ups 2, 4 and 6 years previously (1998, 1996 and 1994) were also recorded. RESULTS: In the year 2000, 17.5% and 16.4% of the young people evaluated had excess weight and obesity, respectively. Between 1994 and 2000 there was an increase (p < 0.05) in obesity (5.9% against 16.4%). 31.8% of the obese young people in the year 2000 were already obese 6 years previously, 18.2% were normal then, but 50% of them were already overweight in 1994. There were no significant differences between sexes. CONCLUSIONS: In the year 2000, 33% of adolescents between 10 and 14 in our health area had a BMI that suggested excess body fat. As excess weight in school students supposes a situation of risk of obesity in adolescence, this demands follow-up and preventive activity.

Adolescent↗

Novel Mediator proteins of the small Mediator complex in Drosophila SL2 cells.

The Mediator complex is generally required for transcriptional regulation in species ranging from yeast to human. Throughout evolution, the functional diversity of the Mediator complex has been enhanced to meet the increasing requirements for sophisticated gene regulation. It is likely that greater structural complexity is thus required to accomplish these new, complex regulatory functions. In this study, we took systematic steps to examine various types of Mediator complexes in Drosophila melanogaster. Such efforts led to the identification of three distinct forms of Mediator complexes. In exploring their compositional and functional heterogeneity, we found that the smallest complex (C1) is highly enriched in a certain type of Drosophila cells and possesses novel Mediator proteins. The subunits shared among the three Mediator complexes (C1, C2, and C3) appear to form a stable modular structure that serves as a binding surface for transcriptional activator proteins. However, only C2 and C3 were able to support activated transcription in vitro. These findings suggest that different cell types may require distinct Mediator complexes, some of which may participate in nuclear processes other than the previously identified functions.

Amino Acid Sequence↗

Phylotranscriptomics Allows Distinguishing Major Gene Flow Events from Incomplete Lineage Sorting in Rapidly Diversifying Mimetic Orchids (Genus Ophrys).

Ophrys orchids (or bee orchids) provide an outstanding example of a plant adaptive radiation. Over the last 5 million years, this genus has diversified into hundreds of taxa as a result of its unconventional pollination strategy, known as "sexual swindling". However, the rapid and substantial diversification of this genus, combined with its capacity for hybridization and large genome size, poses significant challenges in addressing its systematics. We used phylotranscriptomics as a genome complexity reduction technique to infer the phylogenetic relationships among Ophrys main lineages. More than seven thousand gene trees enabled us to determine the relative contributions of gene flow and incomplete lineage sorting (ILS) in Ophrys evolution. First, we propose a new phylogenetic hypothesis for the genus with an unprecedented resolution that largely confirms the relationships between the main Ophrys lineages, but also provides new insights within each subgenera. By combining phylogenetic network inference with introgression analyzes based on gene tree topologies and branch lengths, we then show that the numerous phylogenetic incongruences among gene tree topologies result from a pervasive background of ILS, over which stand out several well-supported, ancient and potentially adaptive gene flow events between lineages. These major gene flow events provide a new perspective on the evolution of the Ophrys genus and its pollination, questioning previous hypotheses inferred without considering its reticulate evolution, and providing a better understanding of discrepancies observed among previous phylogenetic studies of the genus.

Orchidaceae↗

Maximum-entropy closures for kinetic theories of neuronal network dynamics.

We analyze (1 + 1)D kinetic equations for neuronal network dynamics, which are derived via an intuitive closure from a Boltzmann-like equation governing the evolution of a one-particle (i.e., one-neuron) probability density function. We demonstrate that this intuitive closure is a generalization of moment closures based on the maximum-entropy principle. By invoking maximum-entropy closures, we show how to systematically extend this kinetic theory to obtain higher-order, kinetic equations and to include coupled networks of both excitatory and inhibitory neurons.

Algorithms↗

Evolution of practice nursing in Australia.

AIM: This paper describes the evolution of Australian practice nursing and documents seminal events in crystallizing the importance of the nursing role in general practice. BACKGROUND: Internationally, the potential for nurses to improve health in primary care settings is acknowledged. The general practice setting is a focal point for primary care in many health systems. Despite the important role played in the delivery of primary health care by nurses working in general practice in the United Kingdom and New Zealand, the role of nurses in Australian general practice is much less clearly defined, as reflected by the paucity of research and scholarship in this area. Fuelled by the increasing challenges of workforce shortages and the increasing need for multidisciplinary care, interest in the developing role of the Australian practice nurse among clinicians, researchers and policy makers is increasing. DISCUSSION: Australian practice nursing has reached a critical point in its evolution. It is imperative for the promotion of nursing in general practice that knowledge from descriptive, exploratory research be used to inform strategic decision-making in terms of professional development issues, policy, research and scholarship. These data also need to inform systematic outcome studies. To date, the embryonic nature of practice nursing as a discrete professional entity in Australia has inhibited its representation in nursing curricula and professional bodies. CONCLUSION: In order to advance the Australian practice nurse movement and demonstrate its important contribution to primary health care, nurses need to take the lead in strategic planning of this emerging specialty. As well as leadership from an academic, research and policy perspective, clinical leaders need to be fostered among the ranks of practice nurse clinicians to drive clinical practice development and the delivery of evidence-based primary care.

Australia↗

Expression systems for the production of recombinant pharmaceuticals.

The new generation of biological products are largely the result of genetic engineering. The qualitative and quantitative demand for recombinant proteins is steadily increasing. Molecular biologists are constantly challenged by the need to improve and optimise the existing expression systems, and also develop novel approaches to face the demands of producing the complex proteins of tomorrow. This continuous evolution is paralleled by growing concerns about the safety of these novel pharmaceuticals, with health authorities setting high standards for certification. One of the strategies used by researchers in this field involves sourcing new genetic elements for incorporation into expression systems by systematically analysing the rich natural diversity of microorganisms and plant-based expression systems. There are, in addition, numerous tools for modifying microorganisms and for re-engineering existing biological pathways or processes to meet the needs of the pharmaceutical industry. The aim of this review is to present the conventional and alternative expression systems, focusing on prokaryotic expression systems and briefly exploring other complementary recombinant protein production systems and their unique features.

Animals↗

Antirrhinum and Asteridae--evolutionary changes of floral symmetry.

Lamiales s.l., a prominent clade in the Asteridae, commonly have pentamerous monosymmetric flowers with the upper (odd) stamen reduced or lacking. Of the five largest families of the Lamiales s.l. (Gesneriaceae, Scrophulariaceae, Bignoniaceae, Acanthaceae, and Verbenaceae/Lamiaceae), perhaps the most phylogenetically basal, the Gesneriaceae, is the only one with odd staminodes or stamens occurring in all genera. In addition, Gesneriaceae have relatively large odd staminodes often with a differentiation in filament and reduced anther. They also have the largest proportion of genera (approx. 8%) with more or less polysymmetric flowers with five fertile stamens. In the more advanced families of the Lamiales s.l. the pattern varies. In Bignoniaceae an odd staminode is also commonly present. The traditional Scrophulariaceae is the most diverse family with some tribes constantly having an odd staminode (e.g. Antirrhineae) and others missing it (e.g. Manuleae, Pedicularieae), reflecting its probable polyphyly. In Acanthaceae, and still more in Verbenaceae/Lamiaceae with their extremely monosymmetric flowers an odd staminode is more often missing than present. From the systematic distribution of the different floral forms it is most likely that monosymmetric flowers were already present at the base of the Lamiales s.l. but 'reversal' to polysymmetry was still easy in the basal groups with only weak expression of monosymmetry. The evolution of more pronounced monosymmetry proceeded in different lineages and loss of the odd stamen occurred in various clades. The developmentally most intriguing groups are those with loss of the perianth and reduction of floral organ numbers to two or one, Callitriche being the most extreme genus.

Biological Evolution↗

Expression of human blood group antigens A and B in stomach cells of C. carpio, C. auratus, R. ridibunda and H. sapiens.

Human blood group ABH antigens are found not only on red blood cell membranes, but in many other cell types as well. Their biological functions still remain unclear. The aim of the present study was to examine the cellular expression of these antigens in the stomach of representatives of different Vertebrates--Pisces and Amphibia and to compare it with their expression found in Man. The immunohistochemical technique applied was based on the biotinstreptavidin-peroxidase complex. Monoclonal antibodies to human A and B antigens were used as primary antibodies in the system. Stomach paraffin sections from Cyprinus carpio, Carassius auratus, Rana ridibunda and Homo sapiens were examined. Blood group antigens were found mainly in tunica mucosa of C. carpio, C. auratus and R. ridibunda. Tunica muscularis and tunica serosa were always immunonegative. The antigens were localized in the apical part of the cytoplasm of epithelial cells in lamina epithelialis. Strong positive reaction was seen in secretory granules of the stomach of C. auratus, while in R. ridibunda the antigens were expressed by single epithelial cells in cardial stomach glands. A and B antigens were not found in human stomach sections most probably due to the negative secretor status of the individuals studied. Our results show that ABH human blood group antigens are evolutionary conserved structures similarly expressed by different Vertebrates. The phylogenetic stability in their cellular expression possibly results from the important biological role they have. Future large scale systematic investigations could elucidate the undefined and disputable physiological functions of human blood group antigens.

ABO Blood-Group System↗

[Thromboembolus migrating into the right heart in pulmonary embolism. Echocardiographic and clinico-therapeutic aspects in 7 cases and review of the literature].

We report the clinical, echocardiographic and therapeutic aspects and the evolution of 7 cases of right cardiac migrant thromboembolus in pulmonary embolism (5 M and 2 F, aged 43 to 91). Our data are also compared with all the cases reported in the literature (77 patients). During a sample year (1987) we systematically performed two-dimensional echocardiograms (2D Echo) as early as possible in all the patients admitted to our Coronary Care Unit for suspected pulmonary embolism; among 42 patients the diagnosis of pulmonary embolism was confirmed in 30 out of 42 patients. A relatively high incidence of thromboembolus was found (5/30, 17% in 1987); this finding seems to be relative to the early execution of the 2D Echo study (thromboembolus was found in 4/5 patients when 2D Echo was performed within 20 hours and in only 1/23 when 2D Echo was performed later). The 2D Echo was always evocative of freely floating migrant thromboembolus (6 in right atrium, 1 in right ventricle) and no differential diagnosis with thrombi in situ or other masses was necessary. The therapy for 6 patients hospitalized for pulmonary embolism and surviving the first hours (1 patient died immediately) was: surgical in 1 case, medical in the other 5. Medical therapy consisted only of heparin-calcium in one patient and heparin-calcium + dipyridamole in another because of contra-indications for more aggressive therapy. One patient underwent anticoagulant therapy with i.v. heparin. The remaining two underwent fibrinolytic therapy with urokinase and, afterwards, anticoagulant therapy: in 1 case the therapy was started after the embolization of the mass in the pulmonary artery had occurred; in the other one we observed the progressive reduction of thromboembolus until its disappearance within 5 days without any signs of further embolization. All patients survived and were discharged within 25 days, despite the occurrence of lung embolization in 4 of them. The review of 77 cases reported in the literature shows good outcomes for embolectomy when compared with medical therapy, but almost half of the patients underwent surgical therapy directly. Medical therapy experience, particularly with thrombolytic agents (10 cases in all), is still too scarce to exclude its role, as indeed our experience seems to indicate.

Adult↗

Comprehensive survey of carapacial ridge-specific genes in turtle implies co-option of some regulatory genes in carapace evolution.

The turtle shell is an evolutionary novelty in which the developmental pattern of the ribs is radically modified. In contrast to those of other amniotes, turtle ribs grow laterally into the dorsal dermis to form a carapace. The lateral margin of carapacial primordium is called the carapacial ridge (CR), and is thought to play an essential role in carapace patterning. To reveal the developmental mechanisms underlying this structure, we systematically screened for genes expressed specifically in the CR of the Chinese soft-shelled turtle, Pelodiscus sinensis, using microbead-based differential cDNA analysis and real-time reverse transcription-polymerase chain reaction. We identified orthologs of Sp5, cellular retinoic acid-binding protein-I (CRABP-I), adenomatous polyposis coli down-regulated 1 (APCDD1), and lymphoid enhancer-binding factor-1 (LEF-1). Although these genes are conserved throughout the major vertebrate lineages, comparison of their expression patterns with those in chicken and mouse indicated that these genes have acquired de novo expression in the CR in the turtle lineage. In association with the expression of LEF-1, the nuclear localization of beta-catenin protein was detected in the CR ectoderm, suggesting that the canonical Wnt signaling triggers carapace development. These findings indicate that the acquisition of the turtle shell did not involve the creation of novel genes, but was based on the co-option of pre-existing genes.

Animals↗

Improved sampling of the pareto-front in multiobjective genetic optimizations by steady-state evolution: a pareto converging genetic algorithm.

Previous work on multiobjective genetic algorithms has been focused on preventing genetic drift and the issue of convergence has been given little attention. In this paper, we present a simple steady-state strategy, Pareto Converging Genetic Algorithm (PCGA), which naturally samples the solution space and ensures population advancement towards the Pareto-front. PCGA eliminates the need for sharing/niching and thus minimizes heuristically chosen parameters and procedures. A systematic approach based on histograms of rank is introduced for assessing convergence to the Pareto-front, which, by definition, is unknown in most real search problems. We argue that there is always a certain inheritance of genetic material belonging to a population, and there is unlikely to be any significant gain beyond some point; a stopping criterion where terminating the computation is suggested. For further encouraging diversity and competition, a nonmigrating island model may optionally be used; this approach is particularly suited to many difficult (real-world) problems, which have a tendency to get stuck at (unknown) local minima. Results on three benchmark problems are presented and compared with those of earlier approaches. PCGA is found to produce diverse sampling of the Pareto-front without niching and with significantly less computational effort.

Algorithms↗

Evolution of large-subunit rRNA structure. The diversification of divergent D3 domain among major phylogenetic groups.

During evolution, the potential for sequence (and length) variation of large-subunit rRNA has been mostly restricted over 12 divergent domains (termed D1-D12) interspersed along the molecule. Here, we have focused our attention onto the D3 divergent domain, through a detailed analysis of its pattern of variation in the phylogeny, both in terms of primary and secondary structures. We have systematically compared all the procaryotic and eucaryotic sequences published so far (i.e. 36 species), together with a series of 10 additional eucaryotic specimens, which were determined by direct RNA sequencing. Secondary structures supported by comparative evidence have been derived for archaebacteria, eubacteria and eucaryotes respectively, which shows that the D3 domain contains a subset of universally conserved structural features interspersed with four variable subdomains. Within the four portions where a structural diversification has taken place, elementary structures specific of large phylogenetic groups can be identified. Remarkably such diversified structures appear to be preserved despite sequence divergence, suggesting they correspond to functionally important structures. Accordingly, the mode of sequence variation of the D3 domain suggests this region of the molecule may encode elementary functions of rRNA which could have significantly diversified during the evolution of the major groups of organisms.

Animals↗

A high-throughput screen for porphyrin metal chelatases: application to the directed evolution of ferrochelatases for metalloporphyrin biosynthesis.

Porphyrins are of particular interest in a variety of applications ranging from biocatalysis and chemical synthesis to biosensor and electronic technologies as well as cancer treatment. Recently, we have developed a versatile system for the high-level production of porphyrins in engineered E. coli cells with the aim of diversifying substitution patterns and accessing porphyrin systems not readily available through chemical synthesis. However, this approach failed to produce significant amounts of the metalloporphyrin in vivo from overproduced protoporphyrin due to insufficient metal insertion. Therefore, we systematically assessed the activity of the B. subtilis ferrochelatase in vivo and in vitro. A true high-throughput-screening approach based on catalytic in vivo ferrochelatase activity was developed by using fluorescence-activated cell sorting (FACS). This assay was used to screen a library of 2.4 x 10(6) ferrochelatase mutants expressed in protoporphyrin-overproducing recombinant E. coli cells. Several selected protein variants were purified, and their improved catalytic activity was confirmed in vitro. In addition to ferrochelatase activity, metal transport into E. coli was identified as another limitation for in vivo heme overproduction. Overexpression of the metal transporter zupT as part of the assembled pathway increased the overall metalloporphyrin production twofold. This report represents the most exhaustive in vitro evolution study of a ferrochelatase and demonstrates the effectiveness of our novel high-throughput-screening system for directed evolution of ferrochelatases based on their catalytic activity.

Ferrochelatase↗

Neurotological complications after radiosurgery versus conservative management in acoustic neuromas: a systematic review-based study.

OBJECTIVE: Treatment modalities for acoustic neuroma (AN) include surgery, observation and gamma-knife surgery. The aim of this study was to compare neurotological complications resulting from two treatment alternatives to microsurgery: radiosurgery and observation. MATERIAL AND METHODS: We conducted a systematic review of the literature dealing with radiosurgery for AN and compared the rate of neurotological complications in this population with that in a cohort of patients managed conservatively. RESULTS: We found that neurotological complications, namely facial hypoesthesia (p = 0.002), hearing loss (p < 0.05) and hydrocephalus (p = 0.02), were more frequently encountered after radiosurgery than with conservative management. In contrast, we found that the risk of growth of AN is significantly higher with conservative management and that the rate of stability of the tumor did not differ significantly between the two treatments. CONCLUSION: We prefer a conservative management regimen for patients who cannot be operated on for their AN. However, there are some difficulties inherent in this conservative management policy, namely non-compliance and difficulties in establishing the evolution of the tumor.

Facial Neuralgia↗

Fugu genome analysis provides evidence for a whole-genome duplication early during the evolution of ray-finned fishes.

With about 24,000 extant species, teleosts are the largest group of vertebrates. They constitute more than 99% of the ray-finned fishes (Actinopterygii) that diverged from the lobe-finned fish lineage (Sarcopterygii) about 450 MYA. Although the role of genome duplication in the evolution of vertebrates is now established, its role in structuring the teleost genomes has been controversial. At least two hypotheses have been proposed: a whole-genome duplication in an ancient ray-finned fish and independent gene duplications in different lineages. These hypotheses are, however, based on small data sets and lack adequate statistical and phylogenetic support. In this study, we have made a systematic comparison of the draft genome sequences of Fugu and humans to identify paralogous chromosomal regions ("paralogons") in the Fugu that arose in the ray-finned fish lineage ("fish-specific"). We identified duplicate genes in the Fugu by phylogenetic analyses of the Fugu, human, and invertebrate sequences. Our analyses provide evidence for 425 fish-specific duplicate genes in the Fugu and show that at least 6.6% of the genome is represented by fish-specific paralogons. We estimated the ages of Fugu duplicate genes and paralogons using the molecular clock. Remarkably, the ages of duplicate genes and paralogons are clustered, with a peak around 350 MYA. These data strongly suggest a whole-genome duplication event early during the evolution of ray-finned fishes, probably before the origin of teleosts.

Animals↗

Evolution of a series of peptidoleukotriene antagonists: synthesis and structure-activity relationships of 1,6-disubstituted indoles and indazoles.

A perception of structural similarities between two independent series of leukotriene antagonists (one emanating from FPL 55712 and one based upon the leukotrienes themselves) led to the discovery of a novel class of indole and indazole derived antagonists of peptidoleukotrienes. A systematic exploration of C-6 substituted 4-(indol-1-ylmethyl)-3-methoxybenzoic acids identified cyclopentylacetamide and cyclopentylurethane as preferred substituents. The corresponding indazoles were equipotent. These compounds are selective leukotriene antagonists with pKB values of 7.5-7.8 vs LTE4 on guinea pig trachea.

Animals↗

[Macromutation and evolution: the fixation of Goldschmidt's macromutations as species and genus traits. Hairlessness mutations in mammals].

A brief survey of the development of concepts on the role of macromutations in evolution is given. Contrary to Iu. A. Filipchenko (1926, 1927), who introduced the "micro- and macromutation" terms and believed that regularities of macroevolution could not be reduced to microevolutionary processes, the majority of "synthetists" explained any form of evolution by changes in allele frequencies. From the studies of Drosophila homoeotic mutants R. Goldschmidt (1940) developed the concept of "hopeful monsters" and their role in macroevolution. However, the homoeotic mutants are of drastically reduced viability, which allows the gradualists to reject Goldschmidt's ideas. The distribution of hairlessness mutations (hairless, nude etc.) with the monogenic pattern of inheritance in mammals was studied. Hairless mutants are known in Peromyscus, Mus musculus, Rattus rattus, R. norvegicus, Canis familiaris, Ovis aries. Hairlessness as norm is found in 53 among contemporaneous 1037 mammalian genera. Part of these cases (hairlessness in all Cetacea and Sirenia) may be explained in terms of both macromutations and obligatory gradualism. There is no doubt as to the macromutational origin of hairlessness in the bat Cheiromeles and the rodent Heterocephalus (Bathyergidae); the genera systematically and ecologically close to these have normal pelage. It is quite possible that hairlessness of walrus (Odobenus) has the same origin. The appearance and fixation of single Goldschmidt's macromutation cannot yet be considered as a macroevolutionary process, though the possibility of fixation of a macromutation in nature as a species and genus character contradicts strongly the concept of obligatory gradualism of evolution.

Animals↗

A systematic invasive strategy in non-ST elevation acute coronary syndromes: is age a limiting factor?

INTRODUCTION: A systematic invasive therapeutic strategy for acute coronary syndromes (ACS) is currently accepted as safe and effective and evidence is growing for its superiority compared to a conservative attitude. Elderly patients, given their greater susceptibility, are frequently excluded from this approach, and this may limit the potential benefits. OBJECTIVE: To evaluate the influence of age on the characteristics and clinical evolution of patients with ACS treated by an invasive strategy and to determine whether this in itself limits its adoption. METHODS: We retrospectively studied 203 patients admitted for ACS (consecutive and non-selected). considered of medium to high risk after evaluation and treated with glycoprotein IIb/IIIa receptor inhibitors. Of these, 45 patients were aged > or =75 years and they constituted the Elderly group, the remainder constituting the Non-elderly group. Their baseline characteristics, treatment and clinical evolution were analyzed and compared. RESULTS: The Elderly group had more women, although the difference was not statistically significant. Of the other characteristics studied, family history of coronary disease and smoking presented significant differences, both being less frequent among the elderly. There was a non-significant tendency to perform less catheterization in the elderly, the two groups being similar regarding the revascularization therapy chosen. Overall, hemorrhagic complications were more frequent in the Elderly group, but the difference regarding significant hemorrhages did not reach statistical significance. In-hospital mortality was higher in the elderly, but diminished and did not reach statistical significance when only patients in whom catheterization was performed were considered. CONCLUSION: In this population the elderly had more non-significant hemorrhagic complications but their higher in-hospital mortality was not associated with the adoption of an invasive approach. We therefore suggest that age by itself does not limit the adoption of a systematic invasive strategy.

Acute Disease↗