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[Doppler ultrasonography of the common carotid artery in persons of different age].

The author carried out ultrasonography of the common carotid arteries by the method based on Doppler's phenomenon in 100 subjects aged 16--86 years. The maximal, minimal and mean flow velocity, vascular resistance, and symmetry and shape of the recorded curve were evaluated. Early and progressing with age changes were found in the curve indicating decreasing vascular wall elasticity. The maximal flow velocity decreased also rapidly. On the other hand, the mean and the minimal flow velocity and the index of vascular resistance remained without substantial changes up to the age of 70 years. In later age the minimal and mean flow velocity decreased rapidly and the index of vascular resistance increased greatly. This suggested accelerated rate of atherosclerosis development and/or exhaustion of compensatory mechanisms. In 3 cases of considerable asymmetry of the curve was observed caused by asymptomatic stenosis of one artery. Doppler ultrasonography could be useful at the time of intensification and evolution of atherosclerotic changes in the carotid arteries, and their effect on the condition of cerebral circulation.

Adolescent↗
PubMed1989

Dinoflagellates in evolution. A molecular phylogenetic analysis of large subunit ribosomal RNA.

The sequence of the large subunit ribosomal RNA (LsuRNA) gene of the dinoflagellate Prorocentrum micans has been determined. The inferred rRNA sequence [3408 nucleotides (nt)] is presented in its most probable secondary structure based on compensatory mutations, energy, and conservation criteria. No introns have been found but a hidden break is present in the second variable domain, 690 nt from the 5' end, as judged by agarose gel electrophoresis and primer extension experiments. Prorocentrum micans LsuRNA length and G+C content are close to those of ciliates and yeast. The conserved portions of the molecule (1900 nt) have been aligned with corresponding sequences from various eukaryotes, including five protista, one metaphyta, and three metazoa. An extensive phylogenetic study was performed, comparing two phenetic methods (neighbor joining on difference matrix, and Fitch and Margoliash on Knuc values matrix) and one cladistic (parsimony). The three methods led to similar tree topologies, except for the emergence of yeast that groups with ciliates and dinoflagellates when phenetic methods are used, but emerges later in the most parsimonious tree. This discrepancy was checked by statistical analyses on reduced trees (limited to four species) inferred using parsimony and evolutionary parsimony methods. The data support the phenetic tree topologies and a close relationship between dinoflagellates, ciliates, and yeast.

Animals↗
PubMed1992

Evolutionary adaptation to different thermal environments via transcriptional regulation.

Populations of the teleost fish Fundulus heteroclitus are subjected to the clinical variation in environmental temperatures that occurs along the eastern seacoast of North America. In concordance with this change in temperature is the clinal variation in the enzyme concentration of the heart-type lactate dehydrogenase (LDH-B; E.C.1.1.1.27). Previously we have shown that the compensating change in the LDH-B enzyme concentration is due to a change in the amount of LDH-B mRNA, but we did not define whether this was due to differences in mRNA stability or to differences in rate of transcription. The results presented here help clarify the molecular mechanism responsible for the variation in Ldh-B gene expression: the rate of transcription from the Ldh-B locus is significantly different between populations, and this difference is responsible for the compensatory change in LDH-B enzyme concentration.

Adaptation, Biological↗
PubMed2001

Noncoding RNA gene detection using comparative sequence analysis.

BACKGROUND: Noncoding RNA genes produce transcripts that exert their function without ever producing proteins. Noncoding RNA gene sequences do not have strong statistical signals, unlike protein coding genes. A reliable general purpose computational genefinder for noncoding RNA genes has been elusive. RESULTS: We describe a comparative sequence analysis algorithm for detecting novel structural RNA genes. The key idea is to test the pattern of substitutions observed in a pairwise alignment of two homologous sequences. A conserved coding region tends to show a pattern of synonymous substitutions, whereas a conserved structural RNA tends to show a pattern of compensatory mutations consistent with some base-paired secondary structure. We formalize this intuition using three probabilistic "pair-grammars": a pair stochastic context free grammar modeling alignments constrained by structural RNA evolution, a pair hidden Markov model modeling alignments constrained by coding sequence evolution, and a pair hidden Markov model modeling a null hypothesis of position-independent evolution. Given an input pairwise sequence alignment (e.g. from a BLASTN comparison of two related genomes) we classify the alignment into the coding, RNA, or null class according to the posterior probability of each class. CONCLUSIONS: We have implemented this approach as a program, QRNA, which we consider to be a prototype structural noncoding RNA genefinder. Tests suggest that this approach detects noncoding RNA genes with a fair degree of reliability.

Algorithms↗
PubMed1984

[The ambitio-impulse different from narcissism].

We should not let our dynamic drive bog down in the ambiguous concept of "libido". A concept which disturbed Freud himself as is clearly demonstrated in his latest works and which has been considerably misused afterwards. In order to achieve this aim we have in the light of psychopathology, of the symbolic nature of dreams and of our own personal experience set to describe three fundamental drives-the real roots of Man unseparable from his constitution-namely 1. ambitio: (which prompts Man to assert himself, to develop and dominate); 2. agressio: (the urge to defend our internal territory or to overcome obstacles according to our will); 3. attractio: (the disposition to be moved or attracted by this or that object). The present paper shall deal with ambitio which is not to be mixed up with conscious ambition. This unconscious drive, axial and archaic which nourishes the evolution of all living matter (even a tree trunk) should not be interspersed with guilt but is indispensable to our emergence from the Cosmos. Ambitio can be subject to hypertrophy by a compensatory process in cases of megalomania and on the contrary it can be atrophied in the case of a failure syndrome or inferiority complex for example. The most delicate stage of the process is that of its taming and of its conscious acceptance. All things which if properly dealt with and if we want to avoid the traps of authoritarianism or of the narcissistic delusion will lead us in the interest of others, to the most realistic modesty.

Acute Disease↗
PubMed2002

Dobzhansky-Muller incompatibilities in protein evolution.

We study fitness landscape in the space of protein sequences by relating sets of human pathogenic missense mutations in 32 proteins to amino acid substitutions that occurred in the course of evolution of these proteins. On average, approximately 10% of deviations of a nonhuman protein from its human ortholog are compensated pathogenic deviations (CPDs), i.e., are caused by an amino acid substitution that, at this site, would be pathogenic to humans. Normal functioning of a CPD-containing protein must be caused by other, compensatory deviations of the nonhuman species from humans. Together, a CPD and the corresponding compensatory deviation form a Dobzhansky-Muller incompatibility that can be visualized as the corner on a fitness ridge. Thus, proteins evolve along fitness ridges which contain only approximately 10 steps between successive corners. The fraction of CPDs among all deviations of a protein from its human ortholog does not increase with the evolutionary distance between the proteins, indicating that substitutions that carry evolving proteins around these corners occur in rapid succession, driven by positive selection. Data on fitness of interspecies hybrids suggest that the compensatory change that makes a CPD fit usually occurs within the same protein. Data on protein structures and on cooccurrence of amino acids at different sites of multiple orthologous proteins often make it possible to provisionally identify the substitution that compensates a particular CPD.

Amino Acid Sequence↗
PubMed1995

Maintenance of pre-mRNA secondary structure by epistatic selection.

Linkage disequilibrium between polymorphisms in a natural population may result from various evolutionary forces, including random genetic drift due to sampling of gametes during reproduction, restricted migration between subpopulations in a subdivided population, or epistatic selection. In this report, we present evidence that the majority of significant linkage disequilibria observed in introns of the alcohol dehydrogenase locus (Adh) of Drosophila pseudoobscura are due to epistatic selection maintaining secondary structure of precursor mRNA (pre-mRNA). Based on phylogenetic-comparative analysis and a likelihood approach, we propose secondary structure models of Adh pre-mRNA for the regions of the adult intron and intron 2 where clustering of linkage disequilibria has been observed. Furthermore, we applied the likelihood ratio test to the phylogenetically predicted secondary structure in intron 1. In contrast to the other two structures, polymorphisms associated with the more conserved stem-loop structure of intron 1 are in low frequency, and linkage disequilibria have not been observed. These findings are qualitatively consistent with a model of compensatory fitness interactions. This model assumes that mutations disrupting pairing in a secondary structural element are individually deleterious if they destabilize a functionally important structure; a second "compensatory" mutation, however, may restabilize the structure and restore fitness.

Animals↗
PubMed1975

Palatal epithelium of a monotreme and a marsupial.

The palatal epithelium of a monotreme, Tachyglossus aculeatus and a marsupial, Tarsipes spenserae were examined histologically and with the scanning electron microscope. Each animal possess keratinized palatal spines which although histologically similar, show significant differences in their external morphology. It is suggested that the spines in each case are highly differentiated filiform papillae which have developed as a compensatory mechanism of mastication, since both animals are in effect, edentulous. In the light of these findings and observations on the tongue of both animals, it is suggested that a degree of parallel evolution of the palate (as part of the masticatory apparatus) has occurred.

Animals↗
PubMed1998

Karyotypic evolution of cells in culture: a new concept.

The Chapter summarizes peculiarities of karyotypic variability during establishment and long-term cultivation of permanent cell lines. A new concept on pathways of karyotypic evolution of cells in culture is put forward. A detailed description is presented of the author's original approach of cytogenetic analysis of cell lines provided for a principally new characteristic of the cell line: its generalized reconstructed karyotype (GRK). Its use as a criterion to evaluate authenticity, purity, and stability of cell lines is discussed. Based on analysis of the GRK, two stages of karyotype evolution of cell lines are revealed: establishment and stabilization, different in karyotypic variability of the cell population and in peculiarities of clone selection. Comparison of peculiarities of karyotypic variability of leukemic and tumor cells both in vitro and in vivo was made, and general regularities of their karyotypic evolution have been established, such as nonrandom changes in the number and structure of chromosomes and deletion of one of the sex chromosomes, as well as regularities characteristic only of cells in culture in most human and animal cell lines (at least 85%) of disomy on all autosomes. The rest of the cell lines, 15%, are characterized by either partial or total monosomies on certain autosomes during long-term cultivation. Three main compensatory mechanisms of maintaining viability of cell lines that have lost genetic material are discussed: polyploidization of the initial cell clone, amplification of oncogenes (predominantly of mys family), and extracopying of whole autosomes or of their fragments.

Animals↗
PubMed1992

Changes in contractile and non-contractile proteins, intracellular Ca2+ and ultrastructures during the development of right ventricular hypertrophy and failure in rats.

Whether cardiac hypertrophy is a compensatory response or a cause of decompensation has been an interesting and important controversy in cardiology. The purpose of this study is to assess qualitative and quantitative changes in biological factors involved in the evolution and the development of right ventricular hypertrophy (RVH) and right ventricular failure in response to pressure overload in rats with pulmonary hypertension induced by monocrotaline injection, and to clarify the process from compensation to deterioration in cardiac hypertrophy biochemically and morphologically. Significant RVH was produced in rats at 2 weeks after single subcutaneous injection of monocrotaline, and signs of right ventricular failure became obvious at 4 weeks as RVH became more severe. In the right ventricle of these rats, we found that: 1) myosin isoenzymes shifted from V1 to V3 both at 2 and 4 weeks; 2) total collagen content increased, and type III and type V collagens increased with a relative decrease in type I collagen at both 2 and 4 weeks; 3) intracellular Ca2+ transient recorded from isolated myocytes showed a lower peak and slower descent slope compared to those of control rats; 4) ultrastructural changes observed by scanning electron microscopy at 1 and 2 weeks disappeared gradually as heart failure developed, and degeneration or destruction of mitochondria or sarcoplasmic reticulum became remarkable at 3 and 4 weeks. These findings suggest that cardiac hypertrophy might be an ominous sign of cardiac failure rather than a benign adaptive process, at least in this model.

Animals↗
PubMed1986

Late modifications of residual parenchyma after splenic resections.

The increased experience in the field of splenic resections have brought up questions about the evolution of the residual parenchyma. Weight increase and the histologic structure of the splenic remnant were studied during a year following hemisplenectomy in rats. Histological studies show that the residual spleen presents a permanent compensatory hyperplasia rather than a true regeneration. This hyperplasia causes an increase in weight of the residual parenchyma which is moderate and only transitory. Indirect confirmation of findings obtained in rats comes from scintigraphic study of residual human splenic tissue after hemisplenectomy. The residual tissue keeps its original form without increase in volume, and the sectioned surface is always well identified one year after splenic resection.

Animals↗
PubMed1999

Increased fitness of drug resistant HIV-1 protease as a result of acquisition of compensatory mutations during suboptimal therapy.

OBJECTIVE: It is thought as a consequence of continuous replication, HIV-1 has acquired an optimal fitness state and that suboptimal antiretroviral therapy selects for drug resistant variants which show impaired fitness in the absence of the drug. In this paper we studied the evolution and fitness of viral populations appearing in a patient who received protease monotherapy. METHODS: Two factors contributing to fitness, drug resistance and protease catalytic activity, were studied at the enzymatic and virological level. RESULTS: The first drug resistant viral variants that were selected in vivo harboured one to three protease substitutions. These mutants showed reduced protease activity and consequently a reduction in viral replication capacity. During continued in vivo replication of these viruses in the presence of the drug, novel variants harbouring additional substitutions in the viral protease appeared. These variants did not display any further increase in drug resistance but demonstrated clearly increased protease activity. Consequently the replication capacity of these viruses was raised to a level at which they replicated better than the original wild-type virus. CONCLUSION: This study indicates that the viral population in the patient does not have to represent the fittest possible variants, and thus antiretroviral therapy may drive the viral population first through a lower fitness level and then to a higher fitness level.

Amino Acid Sequence↗
PubMed2000

Genetics of survival.

The fields of gerontology and genetics have merged, spawning novel lines of investigation and generating a wealth of new results in recent years. However, the lack of clarity and consistency in the basic definitions upon which the science of gerontology must rest has fostered a certain amount of enduring confusion. Among the unclear issues are the genetic components of life span and the distinction between "normal" and "pathologic" aging. At a time of massive world population aging, such issues have, beyond their scientific importance, a momentous social and economic impact. A simple axiomatic framework, consisting of three definitions and five axioms, is proposed that clarifies the aforementioned issues and reconciles disparate data in gerontology. Based on this framework, a new classification of genes involved in survival is proposed. Within the Compensatory Adaptation Theory of aging, apparent paradoxes are solved and problems in gerontology may be formulated anew.

Adaptation, Physiological↗
PubMed2000

Progression of renal failure in patients with compromised renal function is not always present: evaluation of underlying disease.

BACKGROUND: It has been proposed that, once renal function has been restricted in chronic kidney disease, compensatory hyperfiltration results in a compulsory deterioration of renal function. PATIENTS AND METHODS: In this study, 83 patients originally starting from a serum creatinine (S(crea)) between 2.0 and 5.0 mg/dl were followed for the evolution of renal function. This overall population, with a follow-up (FU) of(M +/- SD) 67 +/- 50 months, was stratified into two groups based upon their slope of 1/S(crea), whereby the median of this slope (-0.0019) was taken as the cut-off value. RESULTS: There was an expected decline of renal function in the group with the lowest slope (group A = progression) whereas renal function remained stable in the group with the highest slope (group B = no progression). This evolution occurred in spite of a similar S(crea) in both groups at the start of the study (group A: 2.45 +/- 0.71 mg/100 ml (n = 41) vs. group B: 2.94 +/- 0.88 mg/100 ml (n = 42); p = ns) and an even higher creatinine clearance in group A (group A: 46.43 +/- 18.65 mg/100 ml(n = 41)vs. group B: 34.03 +/- 20.11 mg/100 ml (n = 42); p = 0.0049). Group B contained a higher number of patients with interstitial nephritis (34/42 = 81% vs. 6/41 = 15%; p < 0.00001) while patients with chronic glomerulopathy could be found especially in group A (23/41 = 56% vs. 8/42 = 19%; p < 0.00001). Proteinuria was continuously higher in group A (start FU: p = 0.0097; FU 72 months: p = 0.0155) and tended to decrease in group B (start FU, 0.89 +/- 1.42 g/l (n = 42) vs. FU 72 months, 0.41 +/- 0.78 g/l (n = 26); p = 0.0474) whereas no significant decrease was observed in group A (start FU, 2.16 +/- 2.83 g/l (n = 41) vs. FU 72 months, 1.77 +/- 0.72 g/l (n = 6); p = ns). CONCLUSION: Within the time limit and patient inclusion criteria of this FU, a compromised renal function does not necessarily result in a further decline. This study points more towards a major role for the underlying nature of renal disease.

Creatinine↗
PubMed1976

Temperature: a "shaping force' in protein evolution.

1. Comparisons of homologous enzymes from species adapted to widely different temperatures reveal that ligand-binding affinities are rigorously conserved. This is interpreted to mean that a critical relationship between ligand-binding ability and intracellular ligand concentrations must be maintained for proper enzymic regulation. 2. The catalytic efficiencies of enzyme homologues differ in temperature-compensatory manners. Activation free energies are proportional to adaptation temperature and, consequently, low-temperature-adapted enzymes have the highest substrate turnover numbers. 3. Temperature compensatory adjustments in catalytic efficiency may be achieved by altering the number of weak bonds that form or break during a catalytic conformational change. Support for this hypothesis comes from the finding that activation enthalpy and activation entropy values co-vary in a regular manner and by magnitudes consistent with different amounts of weak-bond formation/rupture during catalytic activation in differnt enzyme homologues. 4. Adaptive adjustments in ligand-binding energetics may also involve utilization of the energy changes that occur during conformational changes. This mechanism would permit enzymes with identical binding-site chemistries to display adaptively different ligand affinities. 5. The greater heat-stabilities of enzymes from warm-adapted species may cause these enzymes to be less efficient catalysts than cold-adapted heat-labile enzymes. Heat-stable enzymes may have to break more weak bonds during a catalytic conformational change than do cold-adapted enzymes. The requirements for thermal stability and high catalytic efficiency thus appear to force an adaptational 'compromise'.

Adaptation, Physiological↗
PubMed1984

Plasma cortisol transport and primate evolution.

Primates have diverged into three major evolutionary groups: prosimians, Old World primates, and New World primates; the last group is distinguished by high circulating cortisol concentrations and resistance to the action of glucocorticoids. We have studied a large spectrum of primate species within these groups to characterize the phylogenetic relationships of cortisol-binding globulin (CBG) among them. The CBG in each species was found to be glycosylated, as judged from lectin interactions, and to exhibit an electrophoretic mobility similar to that of human CBG. Although the CBG affinity for cortisol differed among species, the effects of changes in temperature on the CBG affinity were similar. Strikingly, the CBG-binding capacity of plasma in the New World primates was 1/10th to 1/100th those in the Old World primates and prosimians, while the CBG-binding affinity for cortisol was lower. The reduced capacity and affinity of CBG result in a markedly higher fraction of unbound plasma cortisol in the New World primates than in the Old World primates or the prosimian species examined. This evolutionary pattern of CBG may be a compensatory mechanism for the target organ resistance to glucocorticoids that characterizes the New World monkeys.

Animals↗
PubMed2003

Molecular circumscription of the hornworts (Anthocerotophyta) based on the chloroplast DNA trnL-trnF region.

In phylogenetic trees generated from partial trnL(UAA) intron sequences, the hornworts (represented by nine species from the genera Anthoceros, Dendroceros, Megaceros, Notothylas and Phaeoceros) are resolved as a monophyletic group and are separated from the clades of mosses, liverworts and tracheophytes. A secondary structure of the trnL(UAA) intron of Anthoceros agrestis is presented, displaying the arrangement of the stem-loop regions P1-P9. Compensatory base-pair changes (coevolutionary sites) are detected in regions P4/5 and P9 within the hornwort sequences. The original homology of the most variable region, P8, cannot be detected anymore due to the extremely fast divergent evolution of this segment in the major land plant groups. Similarly, a high sequence divergence occurs in the trnL-trnF intergenic spacer. Apart from synapomorphic substitutions in the trnL(UAA) intron, the hornworts are characterised by a large P6 region consisting of many repetitive elements. The molecular data therefore support the hornworts as representing an independent land plant lineage (Anthocerotophyta). Although relationships between hornworts and the other land plant groups remain unresolved in the trnL(UAA) intron trees, it is rather unlikely that bryophytes are monophyletic in their traditional circumscription, i.e. comprising hornworts, mosses and liverworts.

Anthocerotophyta↗
PubMed2003

Evolution of calcium antagonists: past, present, and future.

Calcium antagonists were originally introduced as fast-acting vasodilators exhibiting powerful antihypertensive properties. They have now evolved into agents exhibiting a smooth onset and a long duration of action. Early agents, because of their rapid onset of action, were associated with a host of compensatory hemodynamic adverse effects including cardioacceleration and sympathetic stimulation. In contrast, the newer agents appear to retain the antihypertensive properties, but with an improved tolerability profile. Across the cardiovascular disease continuum, the presence of diabetes adds to the risk forcardiovascular events. In diabetic patients with hypertension, multiple drug therapy is clearly indicated. Agents such as calcium antagonists that normalize hemodynamics in this patient population might be expected to demonstrate beneficial effects on mortality. Evidence from the Systolic Hypertension in Europe and the Systolic Hypertension in China trials demonstrated over a 50% reduction in total mortality in the diabetic subgroup in patients treated with calcium antagonists. Among the calcium antagonists, particularly among the dihydropyridine subclasses, the efficacy of the drugs has been accompanied by some side effects, in particular pedal edema. The incidence of pedal edema is dose dependent and is the result of vasodilation and intracapillary hypertension. Newer calcium antagonists demonstrate antihypertensive efficacy similar to that of their predecessors but appear to have a reduced propensity to cause edema.

Amlodipine↗