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PubMed2005

An ancient transcriptional regulatory linkage.

Changes in gene regulatory networks are a major engine for creating developmental novelty during evolution. Conversely, regulatory linkages that survive for very long evolutionary periods might be characteristic of ancient and abstract functions of fundamental utility to all metazoans. The proneural genes, which encode a distinctive family of basic helix-loop-helix (bHLH) transcriptional activators, act to promote neural cell fates in the ectoderm of diverse species. Here we report that these genes have been associated for at least 600-700 million years--since before the cnidarian/bilaterian divergence--with a high-affinity binding site for Hairy/Enhancer of split (Hes) repressor proteins. We suggest that the systematic identification of such ancient and conserved connections will be a powerful means of uncovering the primordial functions of transcription factors and signaling systems.

Animals↗

PubMed2001

[The population treated in the general psychiatric sector in 1993 and 1998. Clinical and demographic evolution].

BACKGROUND: The French information system in public psychiatry sectors does not collect morbidity data for the population being treated, estimated as more than a million persons in 1997. Consequently, two surveys were financed by the "Direction Générale de la Santé" and carried out in 1993 and 1998 in order to specify clinical, social and demographic characteristics of the patients. These surveys allowed a follow-up of evolutions according to the pathology and mode of treatment in a context where outpatient treatments are becoming increasingly frequent. METHODS: A census of the patients was made at a given moment, between one and fifteen days according to the mode of treatment. One sector out of two was surveyed, using a systematic selection process. The ICD-10 was used for diagnosis reference. The same methodology was applied in 1993 and 1998. Comparisons were made with the data supplied by the sectors annually and with the data concerning the general population in order to calculate rates per age groups. RESULTS: Between 1993 and 1998, the number of patients increased by +37% in outpatient care, and in part time care, and decreased by -12% in full time care. Rates for patients increased for all age groups in outpatient and part time care, more particularly for the 35 to 49 years old. Conversely, rates decreased in full time care, above all for patients over seventy. In each mode of treatment, the number of patients presenting mood disorders and neurotic disorders increased more than the average, and the proportion of patients with organic mental disorders and mental retardation decreased. Evolutions were different according to the mode of treatment schizophrenia, schizotypal and delusional disorders, and disorders of adult personality and behaviour. CONCLUSIONS: Recourse to outpatient care and part time care increased considerably over five years but evolutions were markedly different from one diagnosis to another. In full time care, the decrease more particularly concerned certain pathologies and age groups. Three phenomena, with possible interactions, could explain the evolutions observed: the population liable to have recourse to psychiatric care is increasing, health policies have changed and care supply has become diversified, and recourse to psychiatric care is now increasingly accepted.

Adult↗

PubMed2004

A systematic method to identify genomic islands and its applications in analyzing the genomes of Corynebacterium glutamicum and Vibrio vulnificus CMCP6 chromosome I.

MOTIVATION: Some genomic islands contain horizontally transferred genes, which play critical roles in altering the genotypes and phenotypes of organisms, and horizontal gene transfer has been recognized as a universal event throughout bacterial evolution. A windowless method to display the distribution of genomic GC content, the cumulative GC profile, is proposed to identify genomic islands in genomes whose complete genome sequences are available. Two new indices are proposed to assess the codon usage bias and amino acid usage bias in genomic islands. RESULTS: A 211 kb genomic island (CGGI-1) has been identified in the genome of Corynebacterium glutamicum, and three genomic islands VVGI-1, VVGI-2 and VVGI-3, with lengths 167, 40 and 33 kb, respectively, have been identified in the genome of Vibrio vulnificus CMCP6 chromosome I. The CGGI-1 is flanked by two approximately 500 bp direct repeats, and utilizes a Val-tRNA as the integration site. For the VVGI-1 and VVGI-2, each has an integrase gene at 5' junction. All the identified genomic islands show unusual GC content, codon usage and amino acid usage, compared with the rest of the genomes. In addition, it is found that genomic islands are fairly homogenous in terms of GC content variation. An index, h, to quantify the homogeneity of GC content for genomic islands is proposed, and it is shown that h is less than 0.1 for all the genomic islands analyzed. The cumulative GC profile, as well as various indices to assess the codon usage bias, amino acid usage bias and homogeneity of the genomic islands, will be useful in the analysis of other genomes. AVAILABILITY: Programs used in this work and numerical results are available upon request.

Algorithms↗

PubMed2006

Assessing site-interdependent phylogenetic models of sequence evolution.

In recent works, methods have been proposed for applying phylogenetic models that allow for a general interdependence between the amino acid positions of a protein. As of yet, such models have focused on site interdependencies resulting from sequence-structure compatibility constraints, using simplified structural representations in combination with a set of statistical potentials. This structural compatibility criterion is meant as a proxy for sequence fitness, and the methods developed thus far can incorporate different site-interdependent fitness proxies based on other measurements. However, no methods have been proposed for comparing and evaluating the adequacy of alternative fitness proxies in this context, or for more general comparisons with canonical models of protein evolution. In the present work, we apply Bayesian methods of model selection-based on numerical calculations of marginal likelihoods and posterior predictive checks-to evaluate models encompassing the site-interdependent framework. Our application of these methods indicates that considering site-interdependencies, as done here, leads to an improved model fit for all data sets studied. Yet, we find that the use of pairwise contact potentials alone does not suitably account for across-site rate heterogeneity or amino acid exchange propensities; for such complexities, site-independent treatments are still called for. The most favored models combine the use of statistical potentials with a suitably rich site-independent model. Altogether, the methodology employed here should allow for a more rigorous and systematic exploration of different ways of modeling explicit structural constraints, or any other site-interdependent criterion, while best exploiting the richness of previously proposed models.

Bayes Theorem↗

PubMed2000

The untranslated regions of eukaryotic mRNAs: structure, function, evolution and bioinformatic tools for their analysis.

The crucial role of the non-coding portion of genomes is now widely acknowledged. In particular, mRNA untranslated regions are involved in many post-transcriptional regulatory pathways that control mRNA localisation, stability and translation efficiency. A review is given of the most recent research works on the functional characterisation of eukaryotic mRNA untranslated regions. In order to make possible a systematic and detailed sequence analysis of mRNA untranslated regions (UTRs), a non-redundant database of metazoan mRNA untranslated sequences annotated for the occurrence of specific functional elements, UTRdb, was devised. These elements, whose consensus structure has been devised on the basis of experimental assays and of comparative analyses, have been collected in the UTRsite database. A suitable pattern-matching software has been devised to search UTRsite patterns in user-submitted sequences, also assessing their statistical significance. Structural, compositional and evolutionary features of untranslated sequences of metazoan mRNAs have been investigated showing peculiar intra- and interspecific patterns.

Animals↗

PubMed2000

Molecular, functional and ultrastructural characterisation of plastids from six species of the parasitic flowering plant genus Cuscuta.

Plastids of Cuscuta reflexa Roxb., C. subinclusa D. et H., C. gronovii Willd. and C. campestris Yunck. possess thylakoids and contain both chlorophyll a and b in a ratio similar to that of stem tissue of the systematically closely related but 'normal' green Ipomoea tricolor. In contrast, plastids of C. odorata R. et P. and C. grandiflora H.B.K. do not contain any chlorophyll or possess thylakoids. Light-driven electron transport, as measured by oxygen evolution and indicated by analysis of chlorophyll fluorescence, was present in all chlorophyll-containing species. The photosystem II efficiency was low and ranged from 0.511 to 0.687. The plastid rbcL gene could not be detected in C. odorata, but was present in all other tested species. Neither rbcL transcripts nor the large subunit of ribulose-1,5-bisphosphate carboxylase-oxygenase (Rubisco) could be detected in C. odorata and C. grandiflora. Low amounts of the large subunit of Rubisco were detected immunologically in all other Cuscuta species. Apparently, the genus Cuscuta comprises species with different degrees of plastid functionality, ranging from intact chloroplasts, via plastids with impaired protein production and gene expression to plastids with reduced plastome gene content.

Blotting, Northern↗

PubMed2005

Evolutionary experience with immunosuppression in pediatric intestinal transplantation.

BACKGROUND/PURPOSE: Intestinal transplantation has developed to become the standard of care for patients with irreversible intestinal failure who are not responding to total parenteral nutrition. Once considered experimental, it has taken time and much effort for the procedure to become a clinical reality, with final acceptance primarily because of the vastly improved outcomes. Advances and novel modifications in immunosuppression have been at the forefront of these improvements. The authors review their evolutionary experience with intestinal transplantation, particularly relating changes in immunosuppression protocols to improved outcomes. METHODS: From July 1990 to December 2003, 122 children received 129 intestinal containing allografts (70 liver/intestine, 42 isolated intestine, 17 multivisceral). Mean age was 5.3 +/- 5.2 years, and 55% were boys. Indications for transplantation were mostly short gut syndrome. The allografts were cadaveric, ABO identical (except one), with no immunomodulation. Bone marrow augmentation was used in 29% of the recipients since 1995. T-cell lymphoctytotoxic crossmatch was positive in 24% cases. Immunosuppression protocols can be divided into 3 categories: (i) maintenance tacrolimus and steroids (n = 52, 1990-1995, 1997-1998); (ii) addition of induction therapy with cyclophosphamide (n = 16, 1995-1997) then daclizumab (n = 24, 1998-2001). A third immunosuppressive agent was added in either group where increased immunosuppression was indicated; (iii) pretreatment/induction with antilymphocyte conditioning and steroid-free posttransplantation tacrolimus monotherapy (n = 37, 2002-2003). In this later group, if clinically stable at 60 to 90 days posttransplantation, and no recent rejection, the tacrolimus was weaned by decreasing frequency of dosing. RESULTS: The overall Kaplan-Meier patient/graft survival was 81%/76% at 1 year, 62%/60% at 3 years, and 61%/51% at 5 years. Survival continues to improve, with 1-year patient/graft survival being 71%/62%, 77%/75%, and 100%/100% for groups (i), (ii), and (iii), respectively. Acute intestinal allograft rejection has decreased markedly in group (iii). The rate of infectious diseases, such as cytomegalovirus and Epstein-Barr virus, is lowest in group (iii). Graft-versus-host disease has not significantly increased with the latest protocol. Most importantly, the overall level of immunosuppression requirements has decreased markedly, with most patients in group (iii) being on monotherapy. Of these, most had their monotherapy weaned down to spaced doses, something never systematically attempted or achieved in pediatric intestinal transplantation. CONCLUSIONS: Intestinal transplantation has progressed markedly over the last 13 years. Although there have been modifications in all aspects of the procedure, the story of intestinal transplantation has been the evolution of successful immunosuppression regimens. Our latest pretreatment/induction conditioning and posttransplantation monotherapy strategy improves graft acceptance and lowers subsequent immunosuppression dosing requirements. It is expected this will overcome many of the complications related to the previously high immunosuppression requirements. Minimization of immunosuppression with avoidance of steroid therapy offers profound long-term benefits, especially in the pediatric population. The patients still remain challenging and complex in every aspect; however, these advances offer significant hope to both patients and caregivers alike.

Adolescent↗

PubMed1998

Eosinophilia in the returning traveler.

Eosinophilia is one of the most common laboratory abnormalities seen in the returning traveler. Although elevations in peripheral eosinophil levels can occur in a wide variety of disease processes, worldwide, helminth parasites are the major group of infectious agents responsible for eosinophilia. While often directed at helminth infections in their early stages of clinical evolution, the approach to the evaluation of the returning traveler with eosinophilia must consider the many causes of eosinophilia including those not casually related to travel. This article reviews the major parasitic causes of eosinophilia and provides a systematic approach to the evaluation of eosinophilia following travel.

Eosinophilia↗

PubMed2001

Comparative genomics of the human and mouse T cell receptor loci.

The availability of the complete genomic sequences of the human and mouse T cell receptor loci opens up new opportunities for understanding T cell receptors (TCRs) and their genes. The full complement of TCR gene segments is finally known and should prove a valuable resource for supporting functional studies. A rational nomenclature system has been implemented and is widely available through IMGT and other public databases. Systematic comparisons of the genomic sequences within each locus, between loci, and across species enable precise analyses of the various diversification mechanisms and some regulatory signals. The genomic landscape of the TCR loci provides fundamental insights into TCR evolution as highly localized and tightly regulated gene families.

Animals↗

PubMed2001

Peptoid oligomers with alpha-chiral, aromatic side chains: effects of chain length on secondary structure.

Oligomeric N-substituted glycines or "peptoids" with alpha-chiral, aromatic side chains can adopt stable helices in organic or aqueous solution, despite their lack of backbone chirality and their inability to form intrachain hydrogen bonds. Helical ordering appears to be stabilized by avoidance of steric clash as well as by electrostatic repulsion between backbone carbonyls and pi clouds of aromatic rings in the side chains. Interestingly, these peptoid helices exhibit intense circular dichroism (CD) spectra that closely resemble those of peptide alpha-helices. Here, we have utilized CD to systematically study the effects of oligomer length, concentration, and temperature on the chiral secondary structure of organosoluble peptoid homooligomers ranging from 3 to 20 (R)-N-(1-phenylethyl)glycine (Nrpe) monomers in length. We find that a striking evolution in CD spectral features occurs for Nrpe oligomers between 4 and 12 residues in length, which we attribute to a chain length-dependent population of alternate structured conformers having cis versus trans amide bonds. No significant changes are observed in CD spectra of oligomers between 13 and 20 monomers in length, suggesting a minimal chain length of about 13 residues for the formation of stable poly(Nrpe) helices. Moreover, no dependence of circular dichroism on concentration is observed for an Nrpe hexamer, providing evidence that these helices remain monomeric in solution. In light of these new data, we discuss chain length-related factors that stabilize organosoluble peptoid helices of this class, which are important for the design of helical, biomimetic peptoids sharing this structural motif.

Circular Dichroism↗

PubMed2001

Peripheral neuropathy during stavudine-didanosine antiretroviral therapy.

Peripheral neuropathy (PN) is among the most frequent side effects described with nucleoside reverse transcriptase inhibitors (NRTIs). We investigated the incidence, evolution and predictive factors of PN during stavudine (d4T)-didanosine (ddI) combination therapy in 65 HIV infected patients, previously treated with zidovudine and/or zalcitabine (ddC) for at least 3 months. A subset of 16 patients was referred for systematic electromyographic examination at weeks 0 and 24: six among the 16 exhibited nerve conduction abnormalities at day 0, probably related to previous ddC treatment in four of those and to HIV infection in the other two, with worsening of abnormalities in one patient at week 24. In total, seven of the 59 assessable patients (11.8%) exhibited grade 2-3 neuropathy, with a median time of occurrence of 17 weeks. Distal, symmetrical paraesthesias of the extremities were the first symptoms in all the patients; none had motor symptoms. In all the patients, PN resolved rapidly after stopping d4T. There were no statistically different parameters between the seven cases and the other 52 patients according to CD4 T cells, HIV RNA, Centers for Disease Control and Prevention (CDC) stage C or d4T daily dose. In our study, the d4T-ddI combination did not seem to increase the incidence of PN; risk factors for PN could not be identified, probably in part because of the low number of patients with PN.

Adult↗

PubMedDate not supplied

Symbolic representation and visual querying of left ventricular image sequences.

In the evaluation of regional left ventricular function, relevant cardiac disorders manifest themselves not only in static features, such as shape descriptors and motion excursion in end-diastolic and end-systolic frames, but also in their temporal evolution. In common diagnostic practice, such dynamic patterns are analysed by direct inspection of frame sequences through the use of a moviola. This permits only a subjective and poorly defined evaluation of functional parameters, and definitely prevents a systematic and reproducible analysis of large sets of reports. Retrieval by contents techniques may overcome this limitation by permitting the automatic comparison of the reports in a database against queries expressing descriptive properties related to significant pathological conditions. A system is presented which is aimed at investigating the potential of this approach by supporting retrieval by contents from a database of cineangiographic or echocardiographic images. The system relies on a symbolic description of both geometrical and temporal properties of left ventricular contours. This is derived automatically by an image processing and interpretation module and associated with the report at its storage time. In the retrieval stage, queries are expressed by means of an iconic visual language which describes searched content properties over a computer screen. The system automatically interprets iconic statements and compares them against concrete descriptions in the database. This enables medical users to interact with the system to search for motion and shape abnormalities on a regional basis, in single or homogeneous groups of reports, so as to enable both prospective and retrospective diagnosis.

Cineangiography↗

PubMed2006

Hamiltonian analysis of transverse beam dynamics in high-brightness photoinjectors.

A general Hamiltonian suitable for perturbative analysis of rapidly accelerating beams is derived from first principles. With the proper choice of coordinates, the resulting Hamiltonian has a simple and familiar form, yet is able to take into account the rapid acceleration, rf focusing, magnetic focusing, and average space-charge forces in rf photoinjectors. From the linear Hamiltonian, the beam-envelope evolution is solved and analyzed, which better illuminates the invariant-envelope solution as well as the theory of emittance compensation. The third-order nonlinear Hamiltonian is derived and analyzed to some extent. To make the analysis systematic and self-contained, alternative derivations are given for the smoothed ponderomotive rf focusing and the transfer matrix of a rf cavity.

Journal Article↗

PubMed2005

Mapping dark matter with cosmic magnification.

We develop a new tool to generate statistically precise dark matter maps from the cosmic magnification of galaxies with distance estimates. We show how to overcome the intrinsic clustering problem using the slope of the luminosity function, because magnification changes strongly over the luminosity function, while intrinsic clustering only changes weakly. This may allow precision cosmology beyond most current systematic limitations. The Square Kilometre Array is able to reconstruct the projected matter density map at smoothing scale approximately 10' with S/N > or = 1, at the rate of 200-4000 deg2 per year, depending on the abundance and evolution of 21 cm emitting galaxies. This power of mapping dark matter is comparable to, or even better than, that of cosmic shear from deep optical surveys or 21 cm surveys.

Journal Article↗

PubMed2002

[Wolfram syndrome. A new case report].

The WOLFRAM syndrome (SW) is a rare hereditary disorder described for the first time in 1938 as the coexistence of a diabetes mellitus and an optic atrophy to which join frequently a diabetes insipidus and a bilateral deafness. Several genetic studies are current to determine transmission mechanisms, physiopathology of the disorder to update a curative therapy. On the occasion of a new case report we remind the main characteristics of this syndrome. The SW is a rare neurodegenerative disorder characterized by the coexistence of diabetes mellitus, diabetes insipidus, optic atrophy and deafness. Several other manifestations are frequently associated: neurological, urologic and endocrinous abnormalities as well as growth troubles. Only diabetes mellitus and optic atrophy are compulsory for the diagnosis. This Syndrome is transmitted to the autosomic recessive mode. Mitochondrial heredity is in the course of study. The systematic practice of a cerebral IRM during a SW allows finding several malformative abnormalities of which the most typical is the agenesis of the post-pituitary gland. The prognosis of the affection is essentially conditioned by the evoluting complications of the uropathy and the diabetes mellitus. The treatment is symptomatic. Genetic therapy is in.

Adult↗

PubMed1976

[Dorsal tenosynovectomy of the wrist in rheumatoid arthritis. Results obtained in 30 cases].

With reference to a series of thirty synovectomies of the wrist in patients with rheumatoid arthritis, the authors report the results observed after an average interval of three years and six months. There was a remarkable reduction in pain in three-quarters of the cases. On the other hand, loss of mobility was noted in 15 patients. Resection of the cubital head was carried out in half of the cases. This was followed in two cases by internal translocation of the carpus, and in three cases by internal translocation combined with cubital inclination of the hand. The results of the tenddon repairs carried out in six patients have been completely satisfactory. A study of the present cases and of data from the literature confirms the local prophylactic value of tenosynovectomy which may also prevent tendon ruptures. The best result are seen in the less evolutive forms in which the risk of relapse is least, and in cases in which surgery is carried out on stable wrists with cartilage showing little alteration. In the presence of inferior radiocubital arthritis the resection must be systematic as it makes it possible to carry out a complete synovectomy of this joint. The authors compare the value of surgical synovectomy of the wrist with that of radioactive synoviorthesis.

Adult↗

PubMed2002

[Systematics meanders of microsporidia].

Meanders of systematics of Microsporidia. Taxonomical questions of Microsporidia, its systematic position and evolutionary relationship with other Eukaryota are discussed. Utilizations of modern methods of investigations of microsporidians cause new taxonomical troubles. At the present time it is difficult to create a clear hypothesis concerning the phylogeny and evolution of Microsporidia. Most likely they are representatives of a new kingdom of Eukaryota. Existing problems will not be dissolved until new detailed data concerning the new and common species are obtained.

Animals↗

PubMed1990

[Cost-effectiveness analysis of HIV screening in pregnant women in hospitals in the Paris region].

Spontaneous diffusion of HIV screening at the occasion of pregnancy has been especially rapid in France. In April-May 1988, 45% of general practitioners systematically prescribed HIV screening during premarital or prenatal consultations. Experimentation of systematic prenatal HIV screening has been performed for some time in various French maternity hospitals. On the basis of real data concerning HIV screening of more than 15,000 pregnant women between August 1987 and July 1988 in 9 Paris hospitals, a cost-effectiveness analysis has been performed. It showed that the total cost of systematic screening for women admitted to maternity hospitals for prenatal care and whose HIV status was previously unknown, was about 1.5 million French francs (about $240,000) and that 22 new cases of HIV positive were discovered. During the first five months (first period), the mean cost per pregnant woman found to be HIV positive was about 42 to 45,000 FF ($6,700-7,150). A similar calculation over the following months, gave a mean cost 4 times higher. The cost and effectiveness of a selective screening for high risk women were also estimated. In this hypothetical case, 13.6% of women would have been tested, the mean cost of discovering, at the hospital, a new HIV positive pregnant woman would have been 7,500 FF ($1,200) during the first period. The quadrupling of the mean cost of identifying an HIV positive pregnant woman by systematic hospital screening, despite a concomitant increase in prevalence in the population, can be explained only by an increase in prenatal screening prescribed by the private practitioner in ambulatory medicine before the first hospital prenatal visit. The monthly evolution of the proportion of women already screened before consultation in one of the nine maternity hospitals had increased by almost 50% between the beginning and the end of the studied period. An evaluation of a policy of HIV screening during pregnancy depends, at least in the French health care system, on the different ways the ambulatory and hospital sectors complement themselves.

Acquired Immunodeficiency Syndrome↗