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PubMed2004

[The long term (15 years) evolution after valvular replacement with mechanical prosthesis or bioprosthesis between the age of 60 and 70 years].

OBJECTIVE: the aim of this study was to document the choice between prosthesis and bioprosthesis in cases of valvular replacement during the seventh decade of life. METHODS: a retrospective and cooperative study linking eleven cardiac surgical teams and five medical cardiology teams combined 497 subjects born between 1915 and 1925 (average age 64.4 years) who underwent aortic (313 cases) or mitral (184 cases) valvular replacement with mechanical prosthesis (259 cases) or bioprosthesis (238 cases). Information was collected at each centre during the year 2000 on the long term evolution (going back 15 years), in particular on the mortality, non-fatal complications linked to the valve, cardiac complications and extra-cardiac events. These results were subjected to statistical analysis. RESULTS: the operative mortality of this group was 4.8%. The 15 year survival was 46% for the aortic mechanical prostheses, 32% for the aortic bioprostheses (p=0.04). 34% for the mitral bioprostheses and 33% for the mitral mechanical prostheses. Events linked to the valve were more frequent for the mitral valvulopathies than for the aortic valves (49% vs 26%, p<0.001). The absence of events linked to the valve at 15 years was 69% for the aortic mechanical prostheses and 68% for the aortic bioprostheses. This was the case in only 57% of mitral mechanical prostheses and 36% of the mitral bioprostheses (p=0.11). Thromboembolic accidents were three times more frequent in the mitrals than in the aortics (11.5 vs 3.8%, p=0.002). Haemorrhage was four times more frequent for the mechanical prostheses than for the bioprostheses (7.7 vs 2%, p=0.01). The risk of degeneration for the aortic bioprostheses was 20% at 15 years, three times less so after 65 years of age (p=0.03). At 48% it was much higher in the mitral valves at 15 years with no significant difference before and after 65 years of age (p=0.3). CONCLUSION: the current life expectancy of subjects in their seventh decade is important. The greatly elevated risk of bioprosthesis degeneration in the mitral position does not allow this alternative to be advocated before 70 years of age. In the aortic position, this risk is elevated before 65 years of age. It is lower after 65 years old. Nevertheless, this means the risk of reoperation in certain octogenarians must be accepted, balanced with the linear risk of haemorrhagic accidents for which a future reduction is expected thanks to milder anticoagulation for aortic mechanical prostheses and anticoagulation autocontrol.

Age Factors↗

PubMed2005

Breakpoint analysis of the pericentric inversion distinguishing human chromosome 4 from the homologous chromosome in the chimpanzee (Pan troglodytes).

The study of breakpoints that occurred during primate evolution promises to yield valuable insights into the mechanisms underlying chromosome rearrangements in both evolution and pathology. Karyotypic differences between humans and chimpanzees include nine pericentric inversions, which may have potentiated the parapatric speciation of hominids and chimpanzees 5-6 million years ago. Detailed analysis of the respective chromosomal breakpoints is a prerequisite for any assessment of the genetic consequences of these inversions. The breakpoints of the inversion that distinguishes human chromosome 4 (HSA4) from its chimpanzee counterpart were identified by fluorescence in situ hybridization (FISH) and comparative sequence analysis. These breakpoints, at HSA4p14 and 4q21.3, do not disrupt the protein coding region of a gene, although they occur in regions with an abundance of LINE and LTR-elements. At 30 kb proximal to the breakpoint in 4q21.3, we identified an as yet unannotated gene, C4orf12, that lacks an homologous counterpart in rodents and is expressed at a 33-fold higher level in human fibroblasts as compared to chimpanzee. Seven out of 11 genes that mapped to the breakpoint regions have been previously analyzed using oligonucleotide-microarrays. One of these genes, WDFY3, exhibits a three-fold difference in expression between human and chimpanzee. To investigate whether the genomic architecture might have facilitated the inversion, comparative sequence analysis was used to identify an approximately 5-kb inverted repeat in the breakpoint regions. This inverted repeat is inexact and comprises six subrepeats with 78 to 98% complementarity. (TA)-rich repeats were also noted at the breakpoints. These findings imply that genomic architecture, and specifically high-copy repetitive elements, may have made a significant contribution to hominoid karyotype evolution, predisposing specific genomic regions to rearrangements.

Animals↗

PubMed1986

Photoenergetics of octopus rhodopsin. Convergent evolution of biological photon counters?

The enthalpy changes associated with each of the major steps in the photoconversion of octopus rhodopsin have been measured by direct photocalorimetry. Formation of the primary photoproduct (bathorhodopsin) involves energy uptake of about 130 kJ/mol, corresponding to storage of over 50% of the exciting photon energy, and is comparable to the energy storage previously observed in bovine rhodopsin. Subsequent intermediates involve the step-wise dissipation of this energy to give the physiological end-product (acid metarhodopsin) at a level only slightly above the parent rhodopsin. No significant differences in energetics are observed between rhodopsin in microvilli membrane suspensions or detergent dispersions. Use of different buffer systems in the calorimetric experiments shows that conversion of rhodopsin to acid metarhodopsin involves no light-induced protonation change, whereas alkali metarhodopsin photoproduction occurs with the release of one proton per molecule and an additional enthalpy increase of about 50 kJ/mol. Van't Hoff analysis of the effect of temperature on the reversible metarhodopsin equilibrium gives an enthalpy for the acid----alkali transition consistent with this calorimetric result, and the proton release is confirmed by direct observation of light-induced pH changes. Acid-base titration of metarhodopsin yields an apparent pK of 9.5 for this transition, though the pH profile deviates slightly from ideal titration behaviour. We suggest that a high energy primary photoproduct is an obligatory feature of efficient biological photo-detectors, as opposed to photon energy transducers, and that the similarity at this stage between cephalopod and vertebrate rhodopsins represents either convergent evolution at the molecular level or strong conservation of a crucial functional characteristic.

Animals↗

PubMed1989

A glycosylated liver-specific transcription factor stimulates transcription of the albumin gene.

HNF1 is a liver-specific transcription factor that plays the dominant role in determining the cell type-specific in vitro transcription of the albumin gene. Here we report the purification and preliminary characterization of HNF1. HNF1 appears to be heavily glycosylated since it is retained on a wheat germ agglutinin-agarose column and can be eluted from it with N-acetylglucosamine, a property not observed with other factors binding to the albumin promoter. Using in vitro transcription assays we demonstrate that purified HNF1 strongly stimulates albumin promoter activity in spleen nuclear extracts, which are devoid of this factor. Likewise, an artificial promoter consisting of two HNF1 recognition sites in front of a TATA motif is strongly activated by HNF1 in such extracts. In addition to stimulating transcription directly by binding to its cognate site, HNF1 may further enhance albumin promoter activity by interacting cooperatively with other trans-acting factors.

Albumins↗

PubMed1995

Molecular mechanisms of cell-type determination in budding yeast.

Studies of cell-type determination in the yeast Saccharomyces cerevisiae have revealed a regulatory network of proteins that are highly conserved in evolutionary terms. In the past few years, genetic, biochemical, and structural approaches have shown what many of these components do, how they fit together, and how they cooperate to regulate the expression of many different target genes.

Biological Evolution↗

PubMedDate not supplied

Isolation and comparison of the IgM heavy chain constant regions from Australian (Trichosurus vulpecula) and American (Monodelphis domestica) marsupials.

cDNAs encoding IgM heavy chain constant region (Cmu) were isolated from two metatherians (marsupials)--the Australian common brushtail possum (Trichosurus vulpecula) and the South American grey short-tailed opossum (Monodelphis domestica). Analysis of the sequences suggested that they correspond to the secreted form of Cmu in both species. The domain size and structure of the marsupial Cmu sequences were compared with other Cmu sequences and a high degree of conservation throughout vertebrate evolution was observed. Amino acid sequence comparisons revealed a marked level of sequence similarity between the two marsupial sequences (79%), relatively high similarity between the marsupials and eutherians (63%), and lower similarities between marsupials and birds (45%), marsupials and amphibians (47%), marsupials and reptiles (45%) and marsupials and fish (37%). These data allow the incorporation of metatherians into the study of mammalian IgM evolution.

Amino Acid Sequence↗

PubMed1998

Meiotic prophase arrest with failure of chromosome synapsis in mice deficient for Dmc1, a germline-specific RecA homolog.

DMC1 is a meiosis-specific gene first discovered in yeast that encodes a protein with homology to RecA and may be component of recombination nodules. Yeast dmc1 mutants are defective in crossing over and synaptonemal complex (SC) formation, and arrest in late prophase of meiosis I. We have generated a null mutation in the Dmc1 gene in mice and show that homozygous mutant males and females are sterile with arrest of gametogenesis in the first meiotic prophase. Chromosomes in mutant spermatocytes fail to synapse, despite the formation of axial elements that are the precursor to the SC. The strong similarity of phenotypes in Dmc1-deficient mice and yeast suggests that meiotic mechanisms have been highly conserved through evolution.

Adenosine Triphosphatases↗

PubMed2002

Extended parental care in communal social groups.

Recent developments in social insect research have challenged the need for close kinship as a prerequisite for the evolution of stable group living. In a model communal bee species, Lasioglossum (Chilalictus) hemichalceum, previous allozyme work indicated that groups of cooperating adult females are not relatives. Yet at any given time, not all group members perform the risky task of foraging. We previously hypothesized that tolerance for non-foragers was a component of extended parental care, previously known only for kin based social systems. DNA microsatellites were used to study colony genetic structure in order to test this hypothesis. Microsatellite polymorphism was substantial (He = 0.775). Overall intracolony relatedness, mainly of immatures, was low but significant in nine, late season nests (r = 0.136 +/- 0.023), indicating that broods contain five to six unrelated sib ships. Detailed analyses of kinship between pairs of individuals revealed that most pairs were unrelated and most related pairs were siblings. Mothers are absent for 89-91% of the developing immature females, and 97% of developing males. Alternatively, 46% of adult females had neither sibs nor offspring in their nests. These findings indicate that the extended parental care model applies broadly to both kin based and nonkin based social systems in the Hymenoptera.

Age Distribution↗

PubMed2000

Origin of complexity in multicellular organisms.

Through extensive studies of dynamical system modeling cellular growth and reproduction, we find evidence that complexity arises in multicellular organisms naturally through evolution. Without any elaborate control mechanism, these systems can exhibit complex pattern formation with spontaneous cell differentiation. Such systems employ a "cooperative" use of resources and maintain a larger growth speed than simple cell systems, which exist in a homogeneous state and behave "selfishly." The relevance of the diversity of chemicals and reaction dynamics to the growth of a multicellular organism is demonstrated. Chaotic biochemical dynamics are found to provide the multipotency of stem cells.

Cell Communication↗

PubMed1991

Episomal and integrated human papillomavirus in cervical neoplasia shown by non-isotopic in situ hybridisation.

It was postulated that non-isotopic in situ hybridisation (NISH) signal types 1-3 for human papillomavirus in cervical biopsy specimens represent episomal or integrated virus. The aim of this study was to validate this hypothesis by independent molecular techniques. Fresh cervical intraepithelial neoplasia (CIN) and squamous cell cancer (SCC) tissue were examined for NISH signal pattern by hybridising with digoxigenin labelled HPV 16. DNA was extracted from the same samples and analysed by restriction endonuclease digestion and Southern blotting to determine the physical state of the viral genome. Six CIN biopsy specimens showed a type 1 NISH signal for HPV 16. On Southern analysis these biopsy specimens contained only episomal HPV 16. Three SCC with a type 2 NISH signal contained integrated HPV 16 by Southern analysis. Two specimens, a CIN 3 and an SCC with a type 3 NISH signal for HPV 16, showed the presence of both episomal and integrated HPV 16 with conventional Southern analysis and two dimensional gel electrophoresis. These results show that episomal HPV can be reliably determined by NISH type 1 signal, integrated HPV by type 2, and a combination of both episomal and integrated HPV, by a type 3 signal in archival paraffin wax embedded cervical biopsy specimens. This will add another variable to the epidemiological studies of HPV infection. In particular, it will now allow retrospective studies to be done to define the role of episomal and integrated HPV in the evolution of cervical intraepithelial neoplasia and other cervical disease associated with this virus.

Blotting, Southern↗

PubMed2006

Mutualistic stability in the arbuscular mycorrhizal symbiosis: exploring hypotheses of evolutionary cooperation.

The 450-million-year-old symbiosis between the majority of land plants and arbuscular mycorrhizal fungi (AMF) is one of the most ancient, abundant, and ecologically important mutualisms on Earth. Yet, the evolutionary stability of mycorrhizal associations is still poorly understood, as it follows none of the constraints thought to stabilize cooperation in other well-known mutualisms. The capacity of both host and symbiont to simultaneously interact with several partners introduces a unique dilemma; detecting and punishing those exploiting the mutualism becomes increasingly difficult if these individuals can continue to access resources from alternative sources. Here, we explore four hypotheses to explain evolutionary cooperation in the arbuscular mycorrhizal symbiosis: (1) pseudo-vertical transmission and spatial structuring of plant and fungal populations leading to local adaptation of partners; (2) luxury resource exchange in which plants trade surplus carbon for excess fungal nutrients; (3) partner choice allowing partners to associate with better cooperators; and (4) host and symbiont sanctions which actively reward good partners and punish less cooperative ones. We propose that mycorrhizal cooperation is promoted by an exchange of surplus resources between partners and enforced through sanctions by one or both partners. These mechanisms may allow plant and fungal genotypes to discriminate against individuals employing exploitative strategies, promoting patterns of partner choice. Together these selection pressures provide a framework for understanding the stabilization of mycorrhizal cooperation over evolutionary time.

Biological Evolution↗

PubMed2005

Aggressive forms of non-Hodgkin's lymphoma in two patients bearing coinfection of Epstein-Barr and hepatitis C viruses.

Although epidemiologic and experimental data suggest an etiopathogenetic role for both hepatitis C virus (HCV) and Epstein-Barr virus (EBV) infection in development of B-cell non-Hodgkin's lymphoma (NHL), potential interactions between EBV and HCV during progression of B-cell NHL have not yet been fully investigated. In the present study, tumor biopsy specimens from patients with both B-cell NHL and chronic HCV infection (HCV(+)) were analyzed for the presence of EBV-encoded RNA (EBER) by in situ hybridization (ISH). VH and VL gene segments were amplified from tumor biopsy specimen DNA by PCR. EBV infection (EBV(+)) was detected in tumors from 2 of 31 (6%) HCV(+) B-cell NHL patients. Clinical histories of these two EBV(+)/HCV(+) B-cell NHL patients indicated a particularly aggressive course of disease. Chemotherapy failed to induce long lasting remission for either of these EBV(+)/HCV(+) B-cell NHL patients. Amplification of CDR3 of the Ig heavy chain gene from DNA isolated from each EBV(+)/HCV(+) B-cell NHL indicated the presence of monoclonal B-cell expansion. Rearrangement of Ig genes in neoplastic B-cell clones from both EBV(+)/HCV(+) patients was similar to that previously reported for EBV(-)/HCV(+) B-cell NHL patients. Additionally, neoplastic B-cell clones from these two EBV(+)/HCV(+) B-cell NHL patients did not exhibit intraclonal variation. Previous studies have demonstrated that intraclonal variation is common among neoplastic B-cell clones from EBV(-)/HCV(+) patients. EBV infection may have prevented evolution of variant neoplastic B-cell clones by suppressing antibody affinity maturation. Together, these data suggest that EBV infection may cooperate with HCV infection during progression of B-cell NHL in immunocompetent individuals. Such an interaction may accelerate the course of disease in B-cell NHL patients.

Aged↗

PubMed1991

Kinetics of thermal inactivation and quaternary structure symmetry of rabbit muscle glyceraldehyde 3-phosphate dehydrogenase.

Kinetics of thermal inactivation of apo-glyceraldehyde 3-phosphate dehydrogenase have been investigated under various conditions. At most pH values, the loss of enzyme activity takes place in two phases, a fast and a slow phase. The data correspond to the rate equation A = Afast.e-kfast.t + Aslow.e-kslow, where A is the observed residual activity (expressed as % of initial activity) at time t, Afast and Aslow are amplitudes (expressed as % of initial activity, so that Afast + Aslow = 100) and kfast and kslow the rate constants of the fast and slow phases, respectively. At pH 9 or below, Afast = Aslow = 50%. As pH is increased above 9, Afast increases gradually till at pH 10 or above when it accounts for the entire initial activity (single exponential decay). The rate constants of the two phases are strongly affected by the nature of the buffer, temperature and pH, but the amplitudes depend on pH alone. It has been suggested that the tetrameric enzyme exists in two conformations of different molecular symmetry, namely C2 (two pairs of sites of unequal stability, predominating at pH 9 or below) and D2 symmetry (four equivalent sites, predominating at pH 10 or above). The C2 in equilibrium D2 transformation is found to be highly cooperative with midpoint at pH 9.6.

Animals↗

PubMed2002

Timing of transmission and the evolution of virulence of an insect virus.

We used the nuclear polyhedrosis virus of the gypsy moth, Lymantria dispar, to investigate whether the timing of transmission influences the evolution of virulence. In theory, early transmission should favour rapid replication and increase virulence, while late transmission should favour slower replication and reduce virulence. We tested this prediction by subjecting one set of 10 virus lineages to early transmission (Early viruses) and another set to late transmission (Late viruses). Each lineage of virus underwent nine cycles of transmission. Virulence assays on these lineages indicated that viruses transmitted early were significantly more lethal than those transmitted late. Increased exploitation of the host appears to come at a cost, however. While Early viruses initially produced more progeny, Late viruses were ultimately more productive over the entire duration of the infection. These results illustrate fitness trade-offs associated with the evolution of virulence and indicate that milder viruses can obtain a numerical advantage when mild and harmful strains tend to infect separate hosts.

Analysis of Variance↗

PubMed2003

Structural studies on ADP activation of mammalian glutamate dehydrogenase and the evolution of regulation.

Glutamate dehydrogenase (GDH) is found in all organisms and catalyzes the reversible oxidative deamination of L-glutamate to 2-oxoglutarate. Unlike GDH from bacteria, mammalian GDH exhibits negative cooperativity with respect to coenzyme, activation by ADP, and inhibition by GTP. Presented here are the structures of apo bovine GDH, bovine GDH complexed with ADP, and the R463A mutant form of human GDH (huGDH) that is insensitive to ADP activation. In the absence of active site ligands, the catalytic cleft is in the open conformation, and the hexamers form long polymers in the crystal cell with more interactions than found in the abortive complex crystals. This is consistent with the fact that ADP promotes aggregation in solution. ADP is shown to bind to the second, inhibitory, NADH site yet causes activation. The beta-phosphates of the bound ADP interact with R459 (R463 in huGDH) on the pivot helix. The structure of the ADP-resistant, R463A mutant of human GDH is identical to native GDH with the exception of the truncated side chain on the pivot helix. Together, these results strongly suggest that ADP activates by facilitating the opening of the catalytic cleft. From alignment of GDH from various sources, it is likely that the antenna evolved in the protista prior to the formation of purine regulatory sites. This suggests that there was some selective advantage of the antenna itself and that animals evolved new functions for GDH through the addition of allosteric regulation.

Adenosine Diphosphate↗

PubMed1999

Delayed increase in infarct volume after cerebral ischemia: correlations with thrombolytic treatment and clinical outcome.

BACKGROUND AND PURPOSE: Growing experimental evidence indicates that the development of cerebral ischemic damage is slower than previously believed. The aims of this work were (1) to study the evolution of CT hypoattenuation between 24 to 36 hours and 7 days in ischemic stroke patients; (2) to evaluate whether thrombolytic treatment given within 6 hours of stroke affects delayed infarction evolution; and (3) to investigate possible correlations between lesion volume changes over time and clinical outcome. METHODS: Of 620 patients included in the European Cooperative Acute Stroke Study 1 (ECASS1), we selected 450 patients whose control CT scans at day 1 (CT1) and day 7 (CT7) were available. They had been randomly divided into 2 groups: 206 patients had been treated with rtPA and 244 with placebo. CT1 and CT7 were classified according to the location of the infarct. The volume of CT hypoattenuation was measured using the formula AxBxC/2 for irregular volumes. The 95% confidence interval of inter- and intrarater variability was used to determine whether significant changes in lesion volume had occurred between CT1 and CT7. Clinical severity was evaluated by means of the Scandinavian Stroke Scale (SSS) at entry (SSS0) and at day 30 (SSS30). RESULTS: Mean lesion volumes were significantly (P<0.0001) higher at day 7 than at day 1 in all the subgroups of patients and particularly in patients with a subcortical lesion. Of the 450 patients studied, 287 (64%) did not show any significant change in lesion volume between CT1 and CT7, 143 (32%) showed a significant increase and the remaining 20 (4%) a significant decrease. No significant correlation was observed between treatment and lesion evolution between CT1 and CT7. Both clinical scores (SSS0 and SSS30) and degree of neurological recovery were significantly (P<0.05) lower in the subgroup of patients with a significant lesion volume increase than in the other 2 groups. CONCLUSIONS: In approximately two thirds of patients, infarct size is established 24 to 36 hours after stroke onset, whereas in the remaining one third, changes in lesion volume may occur later than the first 24 to 36 hours. Many factors may be responsible for delayed infarct enlargement and for a lower degree of clinical recovery, both of which may occur despite early recombinant tissue plasminogen activator treatment.

Aged↗

PubMed2004

Crystal structure of Bacillus subtilis YckF: structural and functional evolution.

The crystal structure of the YckF protein from Bacillus subtilis was determined with MAD phasing and refined at 1.95A resolution. YckF forms a tight tetramer both in crystals and in solution. Conservation of such oligomerization in other phosphate sugar isomerases indicates that the crystallographically observed tetramer is physiologically relevant. The structure of YckF was compared to with its ortholog from Methanococcus jannaschii, MJ1247. Both of these proteins have phosphate hexulose isomerase activity, although neither of the organisms can utilize methane or methanol as source of energy and/or carbon. Extensive sequence and structural similarities with MJ1247 and with the isomerase domain of glucosamine-6-phosphate synthase from Escherichia coli allowed us to group residues contributing to substrate binding or catalysis. Few notable differences among these structures suggest possible cooperativity of the four active sites of the tetramer. Phylogenetic relationships between obligatory and facultative methylotrophs along with B. subtilis and E. coli provide clues about the possible evolution of genes as they loose their physiological importance.

Amino Acid Sequence↗

PubMed1993

Evolution and aggregulates: role of the Polycomb-group genes of Drosophila.

The Polycomb-group (Pc-G) genes of Drosophila melanogaster are responsible for fixation of the repressed state for other selector genes, mostly homeotic but not exclusively. Different arguments suggest that they work cooperatively by specific recognition and structural modification of their targets. Their pleiotropic mutant phenotypes are strikingly similar to morphological traits used to classify Dipteran groups. I propose that the products of Pc-G genes can form a combinatorial multimeric regulatory system (the Aggregulates of F. Jacob) and that stable variations in the composition of this system have played an important role in Dipteran evolution.

Animals↗