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[Brain stem ischemia in a boy with resistance to C activated protein and elevated lipoprotein A].

INTRODUCTION: Activated protein C resistance is the most common hereditary coagulation abnormality. In the majority of cases it results from a point mutation Arg506-->Gln of the factor V gene, and characterized by a poor anticoagulant response to activated protein C. CLINICAL CASE: We report the clinical case of a 6-year-old obese boy, who presented with acute hemiparesis. A cerebral MRI revealed an area of infarction in the left hemiprotuberance. Further investigation identified activated protein C resistance (heterozygosity for factor V Leiden) and elevation in lipoprotein (a). His mother also had factor V Leiden mutation. Prophylaxis with acetylsalicylic acid was instituted with favorable evolution. CONCLUSIONS: This mutation, isolated, is usually asymptomatic, unless other risk factors coexist. Although venous thromboembolism seems to be the main clinical manifestation, recent reports consider that activated protein C resistance is also a risk factor for arterial thrombosis and stroke in children. We reinforce the need for systematic and thorough evaluation of etiology and risk factors in cases of stroke in children.

Activated Protein C Resistance↗

PubMed1985

[Paraneoplastic palmar erythema].

The authors one human case of symmetric palmar erythema with chronic evolution going before subclinical metastasis of gastric adenocarcinoma. Short review of palmar erythema cases associated with others diseases is presented. They point out the similarity of clinical aspect and iconography with another case associated to Hodgkin disease. Considering the few bibliographical references on this topic, they suggest the systematic investigation of neoplastic disease when a palmar erythema is detected without any other etiology.

Adenocarcinoma↗

PubMed1992

Rate and mode differences between nuclear and mitochondrial small-subunit rRNA genes in mushrooms.

Sequences from homologous regions of the nuclear and mitochondrial small-subunit rRNA genes from 10 members of the mushroom order Boletales were used to construct evolutionary trees and to compare the rates and modes of evolution. Trees constructed independently for each gene by parsimony and tested by bootstrap analysis have identical topologies in all statistically significant branches. Examination of base substitutions revealed that the nuclear gene is biased toward C-T transitions and that the distribution of transversions in the mitochondrial gene is strongly effected by an A-T bias. When only homologous regions of the two genes were compared, base substitutions per nucleotide were roughly 16-fold greater in the mitochondrial gene. The difference in the frequency of length mutations was at least as great but was impossible to estimate accurately because of their absence in the nuclear gene. Maximum likelihood was used to show that base-substitution rates vary dramatically among the branches. A significant part of the rate inconstancy was caused by an accelerated nuclear rate in one branch and a retarded mitochondrial rate in a different branch. A second part of the rate variability involved a consistent inconstancy: short branches exhibit ratios of mitochondrial to nuclear divergences of less than 1, while longer branches had ratios of approximately 4:1-8:1. This pattern suggests a systematic error in the branch length calculation. The error may be related to the simplicity of the divergence estimates, which assumes that all base positions have an equal probability of change.

Base Composition↗

PubMed2026

Genomic Footprints of Historical Introgression Between Ancient Lineages of Wild Oryza AA-Genome Species With Widely Separated Contemporary Distributions.

Phylogenetic incongruence is increasingly recognized as pervasive, yet the extent to which reticulate evolution occurs between groups separated by substantial geographical distances and deep phylogenetic divergence remains poorly characterized. In the Oryza AA-genome group-a model for plant speciation and domestication-the traditional bifurcation model posits that Australian Oryza meridionalis and African Oryza longistaminata occupy basal branches, distinct from the more recently diversified monophyletic clade comprising Asian and other African lineages, including major cultivars. However, recent evidence from endogenous viral sequences has hinted at unexpected genetic relatedness between African O. longistaminata and Asian Oryza sativa, which are geographically and phylogenetically distant. Here, we conducted a genome-wide survey across 11 Oryza species to systematically identify genomic regions exhibiting phylogenetic incongruence. Widespread phylogenetic discordance was observed, notably involving genomic segments in which O. longistaminata showed phylogenetic proximity to Asian species, contradicting their established deep divergence. To distinguish between introgression and incomplete lineage sorting, we performed four-taxon ABBA-BABA tests, which provided statistical support for introgression. Furthermore, divergence time estimates for these incongruent regions were younger than the species divergence times, suggesting historical introgression between the ancestors of lineages that are currently separated by vast geographical distances. Systematic assessments indicated that potential analytical artifacts, such as compositional bias and substitution saturation, were unlikely to explain the observations. These convergent lines of evidence suggest that ancient introgression had occurred between currently geographically separated and evolutionarily divergent Oryza lineages, leaving detectable footprints across their modern genomes.

Oryza↗

PubMed1998

Phylogenetic utility of the nuclear gene arginine decarboxylase: an example from Brassicaceae.

Arginine decarboxylase (ADC) is an important enzyme in the production of putrescine and polyamines in plants. It is encoded by a single or low-copy nuclear gene that lacks introns in sequences studied to date. The rate of Adc amino acid sequence evolution is similar to that of ndhF for the angiosperm family studied. Highly conserved regions provide several target sites for PCR priming and sequencing and aid in nucleotide and amino acid sequence alignment across a range of taxonomic levels, while a variable region provides an increased number of potentially informative characters relative to ndhF for the taxa surveyed. The utility of the Adc gene in plant molecular systematic studies is demonstrated by analysis of its partial nucleotide sequences obtained from 13 representatives of Brassicaceae and 3 outgroup taxa, 2 from the mustard oil clade (order Capparales) and 1 from the related order Malvales. Two copies of the Adc gene, Adc1 and Adc2, are found in all members of the Brassicaceae studied to data except the basal genus Aethionema. The resulting Adc gene tree provides robust phylogenetic data regarding relationships within the complex mustard family, as well as independent support for proposed tribal realignments based on other molecular data sets such as those from chloroplast DNA.

Arabidopsis↗

PubMed2001

Systematic study of occult pulmonary thromboembolism in patients with deep venous thrombosis.

PURPOSE: This study was carried out to evaluate the prevalence and extension of pulmonary thromboembolism (PTE) in symptom-free patients with symptomatic deep venous thrombosis (DVT) of lower limbs and to evaluate their possible implication in the adequate treatment of thromboembolic disease. MATERIALS AND METHODS: We prospectively studied, using noninvasive examination (pulmonary spiral computed tomography [CT] angiography), 159 consecutive patients with acute DVT confirmed by duplex scanning without symptoms of PTE. CT was repeated at 30 days to study evolution of these clinically occult PTE. RESULTS: We observed silent PTE in 65 patients (41%) in all levels of lower limb venous thrombosis. Prevalence of PTE showed significant association with male sex (P =.001) and previously diagnosed heart disease (P =.023). There was no significant association between the level of DVT and the presence of PTE nor the DVT side and thromboembolic pulmonary localization. Of the 65 patients with positive CT exploration results for PTE, 52 had characteristics of acute PTE, 10 had chronic PTE, and 3 patients had both. Chronic PTE was found more frequently in patients with previous episodes of DVT (P =.024). A total of 165 pulmonary artery-affected segments were found at several locations: 5 main, 35 lobar, 58 interlobar, and 67 segmental. Multiple segments were affected in 59% of patients. Repeat CT examinations were performed at 30 days in 53 of 65 patients with positive CT scanning results. In 48 cases (90.6%) PTE had completely disappeared. CONCLUSIONS: Silent PTE occurred frequently in association with clots of lower limbs. The CT scan had a good availability and cost-effectiveness to detect clinically underestimated PTE. The incorporation of this exploration in the systematic diagnostic strategy of most patients with DVT to establish the extension of thromboembolic disease at diagnosis may be useful in the evaluation of added pulmonary artery symptoms and treatment strategies.

Adolescent↗

PubMed2026

Trade-offs in avian parental care: a review of theory and meta-analysis of brood size manipulations.

The selective forces shaping parental care have been studied for over 50 years. While theoretical and experimental work has yielded qualitative progress, the large body of empirical work testing predictions about parental investment based on life-history trade-offs has yet to be synthesized. We first provide an overview of the core life-history theory exploring how selection might shape parental care. We then conduct a systematic review and meta-analysis on studies that experimentally manipulated brood size in birds, a widely used experimental approach to manipulate parental investment. We extracted 313 estimates from 62 studies representing 31 species of birds from 19 different families and tested key predictions on trade-offs in parental care derived from theory. Our analysis provides strong support for some predictions about life-history trade-offs in parental care, but weak or equivocal support for others. Specifically, we found that overall, avian parents respond to brood size manipulations as predicted by life-history theory: they increased care in response to brood enlargement, and decreased care in response to brood reductions. Furthermore, for the same relative manipulation size, responses to brood reductions were greater than responses to brood enlargements. This finding is consistent with predictions derived from life-history theory based on some types of non-linear utility curves. However, many predictions derived from theory are not well supported by our comparative analysis. Species' life-history traits such as clutch size (a measure of current reproduction), adult survival, and broods per year (two measures of future reproduction), explained little, if any, among-species variation in response to brood size manipulations. Several factors may explain this. We highlight that brood size manipulations may affect more than just perception of the value of current reproduction, such as altering parents' perception of predation risk. Importantly, these unintended consequences could lead to asymmetric responses like those we observed. Other common experimental approaches - such as hormone manipulations, altering a partner's effort, and food supplementation - often affect multiple traits or fitness components simultaneously, or may involve cues that poorly match the evolved mechanisms guiding parental behaviour. Our review of both theory and experimental approaches suggests that there are multiple opportunities for more precise experiments. We offer several recommendations for effective designs. One is improved understanding of the biology underlying the functions relating to costs and benefits, with careful consideration of not only how the manipulation will affect only one of those, but also the mechanisms that might alter how parents perceive the manipulation. We also emphasize general principles, such as assessing alternative hypotheses and devising multiple independent tests. Armed with these recommendations, we believe there are new opportunities to increase the strength of inference achieved from studies aimed at understanding the trade-offs affecting the evolution of parental care.

Animals↗

PubMed2004

Evolution and divergence of the genes for cytoplasmic, mitochondrial, and flagellar creatine kinases.

Creatine kinase (CK) plays a central role in energy homeostasis in cells that display high and variable rates of energy turnover. A number of CK genes exist, each being targeted to particular intracellular compartments. In the vertebrates, two genes code for proteins which form homo- and heterodimers targeted to the cytoplasm, while two additional genes code for primarily octameric proteins targeted to the mitochondrial intermembrane space. Yet another gene is present in certain groups which codes for three fused, complete CK domains and is typically targeted to the flagellar membrane of primitive-type spermatozoa. CK is widely distributed in protochordates and both protostome and deuterostome invertebrate groups. The evolutionary relationships of these CK genes have not been fully elucidated. The present communication reports new cDNA-derived deduced amino acid sequences for four cytoplasmic and three mitochondrial CKs and one flagellar CK from lophotrochozoan, protostome invertebrates as well as a new cytoplasmic CK sequence from a protochordate tunicate. These new sequences, coupled with available sequences in the databases and sequences extracted from genome sequencing projects, provide revealing insights into the evolution and divergence of CK genes. Phylogenetic analyses showed that single cytoplasmic, mitochondrial, and flagellar CK genes were present prior to the divergence of the protostomes and deuterostomes. The flagellar CK gene may have evolved within the cytoplasmic gene clade, although the evidence is somewhat equivocal. The two cytoplasmic genes in the vertebrates, and most likely the two mitochondrial genes, evolved after the divergence of the craniates from the protochordates. Comparison of the structure of the genes for selected cytoplasmic, mitochondrial, and flagellar CKs revealed two identical intron boundaries, further reinforcing the notion of a common evolutionary origin, but also showed patterns of changes in structure consistent with each gene type. These studies show that the cytoplasmic, mitochondrial, and flagellar CK genes are rather ancient and that there has been a systematic pattern of duplication and divergence consistent with changing nature of energy demands and physicochemical environment in the cells where they are expressed.

Amino Acid Sequence↗

PubMed2004

Molecular phylogenetics of the Meteoriaceae s. str.: focusing on the genera Meteorium and Papillaria.

In order to delimit and understand the evolution of the Meteoriaceae, we provide phylogenetic analyses using the internal transcribed spacer 2 (ITS2) of nuclear ribosomal DNA in combination with two plastid markers, trnL-F and psbT-H. In contrast to the widely used trnL-F region, the psbT-H gene cluster, coding for proteins of photosystem II, has been rarely used to address systematic questions among the different land plant lineages. To overcome the problem of potential ambiguous alignments of non-coding DNA regions, the data were independently analyzed using direct optimization. The comparison and evaluation of the obtained results showed that the inferred cladograms based on the different phylogenetic approaches are very similar, with only minor differences. In combination with morphological characters, generic relationships as well as taxonomic and nomenclatural problems, especially regarding the key genera Meteorium and Papillaria are discussed in detail. New insights into generic relationships of the Meteoriaceae are provided, such as the exclusion of the monospecific southern South American genera Ancistrodes and Cryphaeophilum, which are subsequently transferred to the Hookeriaceae and Cryphaeaceae, respectively. Phylogenetic reconstructions using maximum likelihood as well as parsimony approaches reveal that at the familial level the Meteoriaceae s. l. are polyphyletic, if the formerly recognized "Trachypodaceae" are considered as a separate family. Based on our results we favor the synonym of the Trachypodaceae with the Meteoriaceae.

Bryopsida↗

PubMed1996

Psychiatrists as treatment team leaders: pitfalls and rewards.

The multidisciplinary treatment team has become a conventional component of inpatient psychiatric care delivery. Treatment team dynamics and their implications for the patient, the team members, the organization, and the team leader in particular have been generally understated in the training of psychiatrists, however, as has its value as a model for learning about administration. This article highlights the history and evolution of the multidisciplinary treatment team in psychiatry, the mix of mental health disciplines, philosophies, and roles involved, the characteristics of mental health care professionals, the conflicting manifest and latent work group tasks, and the dynamics and functions of team leadership. While reviewing information on which to base a systematic approach to team leadership, the author advocates for application of universal standards for education in administrative psychiatry including supervised leadership of multidisciplinary treatment teams and discussions of complimentary readings, examples of which are provided.

Competitive Behavior↗

PubMed2004

A phase cycle scheme that significantly suppresses offset-dependent artifacts in the R2-CPMG 15N relaxation experiment.

R2-CPMG 15N relaxation experiments form the basis of NMR dynamics measurements, both for analysis of nano-pico second dynamics and milli-micro second dynamics (kinetics). It has been known for some time that in the practical limit of finite pulse widths, which becomes acute when using cryogenic probes, systematic errors in the apparent R2 relaxation behavior occur for spins far off-resonance from the RF carrier. Inaccurate measurement of R2 rates propagates into quantitative models such as model-free relaxation analysis, rotational diffusion tensor analysis, and relaxation dispersion. The root of the problem stems from evolution of the magnetization vectors out of the XY-plane, both during the pulses as well as between the pulses. These deviations vary as a function of pulse length, number of applied CPMG pulses, and CPMG inter-pulse delay. Herein, we analyze these effects in detail with experimentation, numerical simulations, and analytical equations. Our work suggests a surprisingly simple change in the phase progression of the CPMG pulses, which leads to a remarkable improvement in performance. First, the applicability range of the CPMG experiment is increased by a factor of two in spectral width; second, the dynamical/kinetic processes that can be assessed are significantly extended towards the slower time scale; finally, the robustness of the relaxation dispersion experiments is greatly improved.

Artifacts↗

PubMed2006

Novel integrative genomics strategies to identify genes for complex traits.

Forward genetics is a common approach to dissecting complex traits like common human diseases. The ultimate aim of this approach was the identification of genes that are causal for disease or other phenotypes of interest. However, the forward genetics approach is by definition restricted to the identification of genes that have incurred mutations over the course of evolution or that incurred mutations as a result of chemical mutagenesis, and that as a result lead to disease or to variations in other phenotypes of interest. Genes that harbour no such mutations, but that play key roles in parts of the biological network that lead to disease, are systematically missed by this class of approaches. Recently, a class of novel integrative genomics approaches has been devised to elucidate the complexity of common human diseases by intersecting genotypic, molecular profiling, and clinical data in segregating populations. These novel approaches take a more holistic view of biological systems and leverage the vast network of gene-gene interactions, in combination with DNA variation data, to establish causal relationships among molecular profiling traits and between molecular profiling and disease (or other classic phenotypes). A number of novel genes for disease phenotypes have been identified as a result of these approaches, highlighting the utility of integrating orthogonal sources of data to get at the underlying causes of disease.

Animals↗

PubMed1997

Multipolar endocardial mapping of the right heart using a basket catheter: acute and chronic animal studies.

The development of catheter-based ablative techniques for primary atrial and ventricular arrhythmias is likely to be assisted by improved techniques for systematic endocardial activation sequence mapping. RA mapping using a multielectrode basket catheter has been shown to be feasible with minimal acute toxicity in a prior study. The objectives of the current study are to investigate: (1) the utility of the basket catheter for mapping RV activation; and (2) the evolution of acute endocardial lesions produced by basket catheter use in both the RA and RV over 4-8 weeks time. A flexible, 5-spoke basket catheter bearing 25 electrode pairs was placed in the RA (n = 9) or the RV (n = 13) in 22 juvenile sheep (22-56 kg). The catheter was deployed for 0.1-4.1 hr (RA) and 0.3-3.9 hr (RV). In 20 of these 22 animals, 32 recordings were made of filtered (30-250 Hz) bipolar electrograms and surface ECG. Electrograms were timed and used to construct activation sequences based on a schematic of catheter geometry. Hearts were examined either acutely (4 RA and 9 RV studies) or 4-8 weeks after the procedure (5 RA and 4 RV studies). One animal undergoing RA placement had an air embolism resulting in cardiac arrest immediately prior to basket placement; all other animals were stable during placement. RA electrograms of sufficient quality to determine activation time were recorded from 82% of pairs in RA maps, and RV electrograms from 89% of pairs in RV maps. Mean activation sequence duration in RV was 16 ms versus 47 ms in RA (P < 0.0001), making construction of RV maps more difficult. Acute postmortem studies of RV placement revealed a silent apical RV puncture in one animal. Superficial abrasion or ecchymosis of RV endocardium and/or tricuspid valve were noted in six animals. Postmortem exams in both RA and RV chronic studies showed healed endocardial lesions, with only superficial scarring. Rapid RV activation mapping using a basket catheter is feasible, but requires precision recording techniques. Endocardial abrasions produced in lambs both by RA and RV placement of the catheter are healed in < 4-8 weeks, with trivial residua. The multielectrode basket catheter may be applicable to the mapping of tachycardias originating in or involving the right ventricle.

Animals↗

PubMed2001

New simulators for the optimum management and operation of wastewater treatment plant.

This paper presents the basic description and the first full-scale implementation of a new kind of simulator specially designed to facilitate and improve the management and operation of modern wastewater treatment plants (WWTP). This new kind of simulator for plant operation is specifically adapted to every WWTP and the software is developed considering the common needs of the operators in plant exploitation. The internal structure of the plant operation simulator is based on a complete connection between the real data and the mathematical model of the plant. The software is then able to perform the processing, storage and management of the plant data and to predict the evolution of the process reading the required inputs from its stored files. The results obtained with the first application recommend the implementation of this new kind of simulators for plant operation in other treatment plants. However, it is important to note that the application of this technology implies a systematic and rigorous methodology in the acquisition and processing of the most significant plant data.

Data Collection↗

PubMed2005

Conservation of Y-linked genes during human evolution revealed by comparative sequencing in chimpanzee.

The human Y chromosome, transmitted clonally through males, contains far fewer genes than the sexually recombining autosome from which it evolved. The enormity of this evolutionary decline has led to predictions that the Y chromosome will be completely bereft of functional genes within ten million years. Although recent evidence of gene conversion within massive Y-linked palindromes runs counter to this hypothesis, most unique Y-linked genes are not situated in palindromes and have no gene conversion partners. The 'impending demise' hypothesis thus rests on understanding the degree of conservation of these genes. Here we find, by systematically comparing the DNA sequences of unique, Y-linked genes in chimpanzee and human, which diverged about six million years ago, evidence that in the human lineage, all such genes were conserved through purifying selection. In the chimpanzee lineage, by contrast, several genes have sustained inactivating mutations. Gene decay in the chimpanzee lineage might be a consequence of positive selection focused elsewhere on the Y chromosome and driven by sperm competition.

Animals↗

PubMed2005

Accuracy of rate estimation using relaxed-clock models with a critical focus on the early metazoan radiation.

In recent years, a number of phylogenetic methods have been developed for estimating molecular rates and divergence dates under models that relax the molecular clock constraint by allowing rate change throughout the tree. These methods are being used with increasing frequency, but there have been few studies into their accuracy. We tested the accuracy of several relaxed-clock methods (penalized likelihood and Bayesian inference using various models of rate change) using nucleotide sequences simulated on a nine-taxon tree. When the sequences evolved with a constant rate, the methods were able to infer rates accurately, but estimates were more precise when a molecular clock was assumed. When the sequences evolved under a model of auto-correlated rate change, rates were accurately estimated using penalized likelihood and by Bayesian inference using lognormal and exponential models of rate change, while other models did not perform as well. When the sequences evolved under a model of uncorrelated rate change, only Bayesian inference using an exponential rate model performed well. Collectively, the results provide a strong recommendation for using the exponential model of rate change if a conservative approach to divergence time estimation is required. A case study is presented in which we use a simulation-based approach to examine the hypothesis of elevated rates in the Cambrian period, and it is found that these high rate estimates might be an artifact of the rate estimation method. If this bias is present, then the ages of metazoan divergences would be systematically underestimated. The results of this study have implications for studies of molecular rates and divergence dates.

Algorithms↗

PubMed2006

Insights into the historical construction of species-rich biomes from dated plant phylogenies, neutral ecological theory and phylogenetic community structure.

Analytical methods are now available that can date all nodes in a molecular phylogenetic tree with one calibration, and which correct for variable rates of DNA substitution in different lineages. Although these techniques are approximate, they offer a new tool to investigate the historical construction of species-rich biomes. Dated phylogenies of globally distributed plant families often indicate that dispersal, even across oceans, rather than plate tectonics, has generated their wide distributions. By contrast, there are indications that animal lineages have undergone less long distance dispersal. Dating the origin of biome-specific plant groups offers a means of estimating the age of the biomes they characterize. However, rather than a simple emphasis on biome age, we stress the importance of studies that seek to unravel the processes that have led to the accumulation of large numbers of species in some biomes. The synthesis of biological inventory, systematics and evolutionary biology offered by the frameworks of neutral ecological theory and phylogenetic community structure offers a promising route for future work.

Animals↗

PubMed2006

Systematics and emerging infectious diseases: from management to solution.

The crisis of emerging infectious disease stems from the absence of comprehensive taxonomic inventories of the world's parasites, which includes the world's pathogens. Recent technological developments raise hopes that the global inventory of species, including potential pathogens, can be accomplished in a timely and cost-effective manner. The phylogenetics revolution initiated by systematists provides a means by which information about pathogen transmission dynamics can be placed in a predictive framework. Increasingly, that information is widely available in digital form on the Internet. Systematic biology is well positioned to play a crucial role in efforts to be proactive in the arena of emerging parasitic and infectious diseases.

Animals↗