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PubMed2004

Development of Y-chromosomal microsatellite markers for nonhuman primates.

We have analysed 136 newly identified human Y-chromosomal microsatellites in five (sub)species of nonhuman primates. We identified 83 male-specific loci for central chimpanzees, 82 for western chimpanzees, 67 for gorillas, 45 for orangutans and 19 loci for mandrills. Polymorphism was detected at 56 loci in central chimpanzees, 29 in western chimpanzees, 24 in western gorillas, 17 in orangutans and at three in mandrills. Success in male-specific amplification of human Y-chromosomal microsatellites in nonhuman primates was significantly negatively correlated with divergence time from the human lineage. We observed significantly more Y-chromosomal microsatellite diversity in central chimpanzees than in western chimpanzees. There were significantly more male-specific loci with longer alleles in humans than with longer alleles in the nonhuman primates; however, this significant difference disappeared when only the loci which are polymorphic in nonhuman primates were analysed, suggesting that ascertainment bias is responsible. This study provides primatologists with a large number of polymorphic, male-specific microsatellite markers that will be valuable for investigating relevant questions in behavioural ecology such as male reproductive strategies, kin-based cooperation among males and male-specific dispersal patterns in wild groups of nonhuman primates.

Animals↗
PubMed2006

Dispersal, philopatry and intergroup relatedness: fine-scale genetic structure in the white-breasted thrasher, Ramphocinclus brachyurus.

Dispersal is a fundamental process influencing evolution, social behaviour, and the long-term persistence of populations. We use both observational and genetic data to investigate dispersal, kin-clustering and intergroup relatedness in the white-breasted thrasher, Ramphocinclus brachyurus, a cooperatively breeding bird that is globally endangered. Mark-resighting data suggested sex-biased dispersal, with females dispersing over greater distances while males remained philopatric. Accordingly, spatial autocorrelation analysis showed highly significant fine-scale genetic structure among males, but not among females. This fine-scale genetic structuring of the male population resulted in very high levels of relatedness between dominant males at neighbouring nests, similar to that seen within cooperative groups in many species where kin selection is cited as a cause of cooperation. By implication, between-group as well as within-group cooperation may be important, potentially creating a feedback loop in which short-distance dispersal by males leads to the formation of male kin clusters that in turn facilitate nepotistic interactions and favour further local recruitment. The strength of spatial autocorrelation, as measured by the autocorrelation coefficient, r, was approximately two to three times greater than that reported in previous studies of animals. Relatively short dispersal distances by both males and females may have a negative impact on the white-breasted thrasher's ability to colonize new areas, and may influence the long-term persistence of isolated populations. This should be taken into account when designating protected areas or selecting sites for habitat restoration.

Animal Migration↗
PubMed1995

Using patient surveys to measure health plan performance and improve quality of care.

The market place is demanding more information about health plan performance. Employer efforts to restrain increasing premium costs have spawned numerous business coalition initiatives to obtain and analyze performance information. Employer and health plan cooperation on the development of the Health Plan Employer Data Information Set (HEDIS) represents progress toward standardizing data capture, but the complexity of the information does not lend itself to consumer use. This article explores the evolution of the demand for health care performance information and the role of member/employee satisfaction surveys as a tool to capture meaningful data to help measure performance and improve quality.

Data Collection↗
PubMed2002

Treatment options in pediatric epilepsy syndromes.

Recent evidence suggests that various epilepsy syndromes respond differently to antiepileptic drugs. It follows that a more precise diagnosis, together with a better understanding of AED mechanisms of action, enables them to be used more specifically, and therefore more effectively. Patient characteristics including age of onset, seizure frequency, EEG data and the findings of imaging studies, provide diagnostic pointers which enable the physician to reach a syndrome diagnosis and to choose the most appropriate AED for the individual patient. Home videotapes of paroxysmal events are becoming increasingly available and are often of great assistance. Parents should be encouraged to record their children's attacks. Careful history-taking and correct interpretation of clinical data remain the cornerstones of accurate diagnosis and successful treatment. However, the specificity of antiepileptic drugs is relatively limited and often pharmacotherapy should start using an agent with a broad spectrum of activity appropriate for the primary seizure type. It is in fact common that several antiepileptic agents have similar or identical effectiveness for one particular form of epilepsy. Therefore, the eventual side effects and the greater or lesser difficulties in handling the drug play an essential role in the choice of a therapeutic agent. Polypharmacy should be avoided and surgery should be considered early for selected patients, particularly children, who fail to respond to an appropriate drug trial. Correct diagnosis and the first drug(s) used may have a crucial impact on the evolution of given epilepsy. One major emphasis in the management of epilepsy is on information that should be complete, adapted to the level of understanding, and objective, although given in a positive manner. The understanding and cooperation of children and their families is clearly decisive for the success of therapy, and this requires a confident relationship between the physician and the patient. Current knowledge, on antiepileptic drugs options in paediatric epilepsy syndromes, is discussed.

Adrenocorticotropic Hormone↗
PubMed1980

Clays in prebiological chemistry.

In this review an attempt is made to highlight the structures and properties of clay that may contribute to a better understanding of the role of clays in chemical evolution. The adsorption of organic molecules on clays has been demonstrated, as has the synthesis of bioorganic monomers in the presence of clays. For instance, amino acids (glycine, aspartic acid, threonine, alanine and others) as well as purines and pyrimidines, have been obtained from CO and NH3 in the presence of clays at relatively high temperatures (250-325 degrees C). Carbohydrates are also easily derived from formaldehyde at relatively low temperatures (approximately equal to 80 degrees C). The oligomerization of biochemical monomers, mediated by clays has also been shown to result in the formation of polymer molecules basic to life. For instance the condensation of amino acyl adenylates at room temperature in the presence of montmorillonite is known to yield polypeptides in discrete ranges of molecular weights with degrees of polymerization up to 56. Clays have also been found to affect the condensation of mononucleotides to oligonucleotides. Although the role of clays in the origin or metabolic pathways has not been demonstrated, it is possible that clays may have played a cooperative role with catalytic peptides in an intermediate stage of prebiological chemistry preceding the emergence of life on this planet.

Adsorption↗
PubMed2005

Comparative analysis of gnathostome Otx gene expression patterns in the developing eye: implications for the functional evolution of the multigene family.

We have performed a detailed analysis of the expression pattern of the three gnathostome Otx classes in order to gain new insights into their functional evolution. Expression patterns were examined in the developing eye of a chondrichthyan, the dogfish, and an amniote, the chick, and compared with the capacity of paralogous proteins to induce a pigmented phenotype in cultured retina cells in cooperation with the bHLH-leucine zipper protein Mitf. This analysis indicates that each Otx class is characterized by highly specific and conserved expression features in the presumptive RPE, where Otx1 and Otx2, but not Otx5, are transcribed at optic vesicle stages, in the differentiating neural retina, where Otx2 and Otx5 show a conserved dynamic expression pattern, and in the forming ciliary process, a major site of Otx1 expression. Furthermore, the paralogous proteins of the dogfish and the mouse do not display any significant difference in their capacity to induce a pigmented phenotype, suggesting a functional equivalency in the specification and differentiation of the RPE. These data indicate that specific functions selectively involving each Otx orthology class were fixed prior to the gnathostome radiation and highlight the prominent role of regulatory changes in the functional diversification of the multigene family.

Animals↗
PubMed1976

Synergetic Cultures of Glycine max Root Cells and Rhizobia Separated by Membrane Filters.

When suspension cultures of actively growing soybean (Glycine max L.) root cells were separated by two or three membrane filters from suspension cultures of the bacteria, a synergetic (cooperative) activation of nitrogenase was observed in the Rhizobium japonicum used in the bacterial side. Either plant cells or plant cell-conditioned medium was needed for this activation to take place. Both acetylene reduction and hydrogen evolution by the activated R. japonicum persisted for several days after removal from the apparatus when (a) a suitable carbon source was provided, (b) oxygen supply was limited, and (c) growth of bacteria was suppressed by lowering of ammonia and nitrate concentrations. Activation could also take place when the bacteria were placed in media to which plant cell-conditioned medium was added. The advantages of this method for studies on symbiosis are discussed.

Journal Article↗
PubMed1997

In vivo sequence changes of HIV-1 envelope V2 and V3 loops.

Human immunodeficiency virus type 1 (HIV-1) circulates in vivo as heterogeneous mixed populations (quasispecies). We analyzed the quasispecies nature of the first, second, and third hypervariable loops (V1, V2, and V3) of the gp 120 in plasma and viral isolates obtained from 19 infected individuals. Sequence analysis of 7 SI and 10 NSI isolates showed that the increased positive charge in V3 and elongation of V1 clearly correlated with viral SI capability in PBMC. Contrary to the previous report (M. Groenink et al. Science 260: 1513-1525, 1993), there appeared to be no correlation between SI or non-SI phenotype and length of V2. However, all the 5 isolates with long V2 and basic V3 showed SI phenotype, whereas 4 out of 6 isolates with short V2 and basic V3 showed NSI phenotype, still suggesting some functional cooperation of V2 and V3 on viral syncytium inducing capability. Sequence analysis of HIV-1 in plasma showed the positive correlation between V3 charge and V1 or V2 length in 4 cases. This result suggests the associated evolution of V1/V2 and V3 in these cases.

Cloning, Molecular↗
PubMed2003

The cook, the thief, his wife and her lover: on the evolution of the human reproductive strategy.

Human reproductive strategy differs from that of most other mammals, including Apes such as the closely related chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). For example, humans, although basically polygamic, exhibit a strong tendency to (serial) monogamy and--very rare for a mammal--provide biparental care. Moreover, humans are (almost) permanently willing to mate but, in contrast to other species, do so only in private. Unlike chimpanzees and bonobos, the human female exhibits no external signs of ovulation; rather a number of bodily features, e.g. permanently swollen milk glands and the quality of skin and hair, indicate fitness to breed. Human males also exhibit qualities that are rare among mammals: fertile males can be in the company of fertile females without sex being an imperative--although the awareness of sexuality is generally omnipresent. Moreover, unlike most other Apes, human males can cooperate in large groups, in spite of their polygynic inclination and their tendency to compete with each other for access to females. This capacity probably evolved in response to the necessity to acquire food, in particular meat, which was difficult to obtain by a single man. But life in large, complex, multi-male, multi-female groups places great demands on the members' social skills and, to be able to meet these demands, a large, sophisticated brain (neocortex) is needed. Food (and in its wake, cooking) probably forced man to live in ever-larger groups and to evolve the capacity to cooperate. This, in its turn, drove man's present-days psychosocial (emotional and intellectual) make-up. But for this to evolve, an adaptation of reproductive strategy was a conditio sine qua non.

Animals↗
PubMed1984

T-lymphocyte and B-lymphocyte dichotomy in anuran amphibians: II. Further investigations on the E-rosetting lymphocyte by using monoclonal antibody azathioprine inhibition and mitogen-induced polyclonal expansion.

We have continued to search for characteristics of T-lymphocytes in anuran amphibians. Inhibition assays using the monoclonal antibodies OKT-11 and T-11, the T-cell immunosuppressive drug azathioprine, and mitogens confirmed the nature of E-rosetting peripheral blood lymphocytes (PBL) in Rana pipiens. Both monoclonal antibodies specifically inhibited E-rosetting in a dose-dependent fashion; absorption of the monoclonals by frog PBL specifically removed inhibition on human E-rosetting T-cells. Lysostripping frog E-receptors with monoclonals and a second FITC antibody revealed a fluorescent lymphocyte population which capped off the receptor as shown by subsequent inhibition of E-rosetting. Significant resynthesis of E-receptors occurred 24 hours after lysostripping, especially in nylon wool effluent fractions. Azathioprine allowed us to define tentatively two subpopulations of E-rosetting lymphocytes: one nylon wool adherent and sensitive to inhibition at low concentrations and another resistant but sensitive to higher (cytotoxic) concentrations of azathioprine. In addition, T-cell but not B-cell mitogens induced expansion of E-rosetting cell populations. Our results support a thymic origin for Rana pipiens' E-rosetting cells. With respect to evolution, human and frog E-receptors are probably homologous, sharing at least one and probably two different antigenic determinants.

Animals↗
PubMed2003

How clonal is Staphylococcus aureus?

Staphylococcus aureus is an important human pathogen and represents a growing public health burden owing to the emergence and spread of antibiotic-resistant clones, particularly within the hospital environment. Despite this, basic questions about the evolution and population biology of the species, particularly with regard to the extent and impact of homologous recombination, remain unanswered. We address these issues through an analysis of sequence data obtained from the characterization by multilocus sequence typing (MLST) of 334 isolates of S. aureus, recovered from a well-defined population, over a limited time span. We find no significant differences in the distribution of multilocus genotypes between strains isolated from carriers and those from patients with invasive disease; there is, therefore, no evidence from MLST data, which index variation within the stable "core" genome, for the existence of hypervirulent clones of this pathogen. Examination of the sequence changes at MLST loci during clonal diversification shows that point mutations give rise to new alleles at least 15-fold more frequently than does recombination. This contrasts with the naturally transformable species Neisseria meningitidis and Streptococcus pneumoniae, in which alleles change between 5- and 10-fold more frequently by recombination than by mutation. However, phylogenetic analysis suggests that homologous recombination does contribute toward the evolution of this species over the long term. Finally, we note a striking excess of nonsynonymous substitutions in comparisons between isolates belonging to the same clonal complex compared to isolates belonging to different clonal complexes, suggesting that the removal of deleterious mutations by purifying selection may be relatively slow.

Alleles↗
PubMed1999

Discretized torsional dynamics and the folding of an RNA chain.

The aim of this work is to implement a discrete coarse codification of local torsional states of the RNA chain backbone in order to explore the long-time limit dynamics and ultimately obtain a coarse solution to the RNA folding problem. A discrete representation of the soft-mode dynamics is turned into an algorithm for a rough structure prediction. The algorithm itself is inherently parallel, as it evaluates concurrent folding possibilities by pattern recognition, but it may be implemented in a personal computer as a chain of perturbation-translation-renormalization cycles performed on a binary matrix of local topological constraints. This requires suitable representational tools and a periodic quenching of the dynamics for system renormalization. A binary coding of local topological constraints associated with each structural motif is introduced, with each local topological constraint corresponding to a local torsional state. This treatment enables us to adopt a computation time step far larger than hydrodynamic drag time scales. Accordingly, the solvent is no longer treated as a hydrodynamic drag medium. Instead we incorporate its capacity for forming local conformation-dependent dielectric domains. Each translation of the matrix of local topological constraints (LTM's) depends on the conformation-dependent local dielectric created by a confined solvent. Folding pathways are resolved as transitions between patterns of locally encoded structural signals which change within the 1 ns-100 ms time scale range. These coarse folding pathways are generated by a search at regular intervals for structural patterns in the LTM. Each pattern is recorded as a base-pairing pattern (BPP) matrix, a consensus-evaluation operation subject to a renormalization feedback loop. Since several mutually conflicting consensus evaluations might occur at a given time, the need arises for a probabilistic approach appropriate for an ensemble of RNA molecules. Thus, a statistical dynamics of consensus formation is determined by the time evolution of the base pairing probability matrix. These dynamics are generated for a functional RNA molecule, a representative of the so-called group I ribozymes, in order to test the model. The resulting ensemble of conformations is sharply peaked and the most probable structure features the predominance of all phylogenetically conserved intrachain helices tantamount to ribozyme function. Furthermore, the magnesium-aided cooperativity that leads to the shaping of the catalytic core is elucidated. Once the predictive folding algorithm has been implemented, the validity of the so-called "adiabatic approximation" is tested. This approximation requires that conformational microstates be lumped up into BPP's which are treated as quasiequilibrium states, while folding pathways are coarsely represented as sequences of BPP transitions. To test the validity of this adiabatic ansatz, a computation of the coarse Shannon information entropy sigma associated to the specific partition of conformation space into BPP's is performed taking into account the LTM evolution and contrasted with the adiabatic computation. The results reveal a subordination of torsional microstate dynamics to BPP transitions within time scales relevant to folding. This adiabatic entrainment in the long-time limit is thus identified as responsible for the expediency of the folding process.

Algorithms↗
PubMed2004

Overlapping CRE and E box motifs in the enhancer sequences of the bovine leukemia virus 5' long terminal repeat are critical for basal and acetylation-dependent transcriptional activity of the viral promoter: implications for viral latency.

Bovine leukemia virus (BLV) infection is characterized by viral latency in a large proportion of cells containing an integrated provirus. In this study, we postulated that mechanisms directing the recruitment of deacetylases to the BLV 5' long terminal repeat (LTR) could explain the transcriptional repression of viral expression in vivo. Accordingly, we showed that BLV promoter activity was induced by several deacetylase inhibitors (such as trichostatin A [TSA]) in the context of episomal LTR constructs and in the context of an integrated BLV provirus. Moreover, treatment of BLV-infected cells with TSA increased H4 acetylation at the viral promoter, showing a close correlation between the level of histone acetylation and transcriptional activation of the BLV LTR. Among the known cis-regulatory DNA elements located in the 5' LTR, three E box motifs overlapping cyclic AMP responsive elements (CREs) in U3 were shown to be involved in transcriptional repression of BLV basal gene expression. Importantly, the combined mutations of these three E box motifs markedly reduced the inducibility of the BLV promoter by TSA. E boxes are susceptible to recognition by transcriptional repressors such as Max-Mad-mSin3 complexes that repress transcription by recruiting deacetylases. However, our in vitro binding studies failed to reveal the presence of Mad-Max proteins in the BLV LTR E box-specific complexes. Remarkably, TSA increased the occupancy of the CREs by CREB/ATF. Therefore, we postulated that the E box-specific complexes exerted their negative cooperative effect on BLV transcription by steric hindrance with the activators CREB/ATF and/or their transcriptional coactivators possessing acetyltransferase activities. Our results thus suggest that the overlapping CRE and E box elements in the BLV LTR were selected during evolution as a novel strategy for BLV to allow better silencing of viral transcription and to escape from the host immune response.

5' Untranslated Regions↗
PubMed2004

Evolutionary conservation and selection of human disease gene orthologs in the rat and mouse genomes.

BACKGROUND: Model organisms have contributed substantially to our understanding of the etiology of human disease as well as having assisted with the development of new treatment modalities. The availability of the human, mouse and, most recently, the rat genome sequences now permit the comprehensive investigation of the rodent orthologs of genes associated with human disease. Here, we investigate whether human disease genes differ significantly from their rodent orthologs with respect to their overall levels of conservation and their rates of evolutionary change. RESULTS: Human disease genes are unevenly distributed among human chromosomes and are highly represented (99.5%) among human-rodent ortholog sets. Differences are revealed in evolutionary conservation and selection between different categories of human disease genes. Although selection appears not to have greatly discriminated between disease and non-disease genes, synonymous substitution rates are significantly higher for disease genes. In neurological and malformation syndrome disease systems, associated genes have evolved slowly whereas genes of the immune, hematological and pulmonary disease systems have changed more rapidly. Amino-acid substitutions associated with human inherited disease occur at sites that are more highly conserved than the average; nevertheless, 15 substituting amino acids associated with human disease were identified as wild-type amino acids in the rat. Rodent orthologs of human trinucleotide repeat-expansion disease genes were found to contain substantially fewer of such repeats. Six human genes that share the same characteristics as triplet repeat-expansion disease-associated genes were identified; although four of these genes are expressed in the brain, none is currently known to be associated with disease. CONCLUSIONS: Most human disease genes have been retained in rodent genomes. Synonymous nucleotide substitutions occur at a higher rate in disease genes, a finding that may reflect increased mutation rates in the chromosomal regions in which disease genes are found. Rodent orthologs associated with neurological function exhibit the greatest evolutionary conservation; this suggests that rodent models of human neurological disease are likely to most faithfully represent human disease processes. However, with regard to neurological triplet repeat expansion-associated human disease genes, the contraction, relative to human, of rodent trinucleotide repeats suggests that rodent loci may not achieve a 'critical repeat threshold' necessary to undergo spontaneous pathological repeat expansions. The identification of six genes in this study that have multiple characteristics associated with repeat expansion-disease genes raises the possibility that not all human loci capable of facilitating neurological disease by repeat expansion have as yet been identified.

Animals↗
PubMed2004

[Nursing role in cardiac prevention].

The lack of a multidisciplinary approach is certainly among the causes of the ineffectiveness of intervention in the field of cardiovascular secondary prevention. By multidisciplinary approach is meant involving cardiologists, nurses, rehabilitation therapists, dieticians as well as psychologists in the framing of interventions tailor made to patients needs. In particular, people working in the nursing area can play a very important role which can be summed up into three different levels: a technical level, aiming at the cooperation with cardiologists to carry out diagnostic examinations and give a portrait of patients in terms of risks; a second level consists in giving information, and helping to face the disease, as well as stepping in during its evolution, almost a health counsellor for the patients; finally the nurse can act as a psychological support both to the patient and his/her family during acute illnesses and reassure him/her that he/she is being treated properly and that successively will resume a good quality of life. Hospital represent an ideal place for secondary prevention, at least in the first phases of the intervention. The results collected during hospitalization would be rapidly lost if they were not followed and sustained in the medium-long term by structured follow-up programmes. The development of ambulatories might represent a link between hospitals and the territory, i.e. the specialist and one's personal physician. The staff of ambulatories should comprise a cardiologist and a trained professional nurse, this being specialized, specifically, in cardiology and cardiovascular prevention. Staff of the type described could work independently, co-ordinating ambulatories on the territory within the framework of standardized recognized protocols and relating information concerning patients, general practitioners and other surgeries. In this way, an essential link of the continuity in medical care would be guaranteed.

Cardiovascular Diseases↗