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PubMed2001

Evolution in silico and in vitro: the RNA model.

Theoretical concepts and experiments dealing with the evolution of molecules in vitro reached a state that allows for direct applications to the design of biomolecules with predefined properties. RNA evolution in vitro represents a basis for the development of a new and comprehensive model of evolution, focusing on the phenotype and its fitness relevant properties. Relations between genotypes and phenotypes are described by mappings from genotype space onto a space of phenotypes, which are many-to-one and thus give ample room for neutrality as expressed by the existence of extended neutral networks in genotype space. The RNA model reduces genotype-phenotype relations to mappings from sequences into secondary structures of minimal free energies and allows for derivation of otherwise inaccessible quantitative results. Continuity and discontinuity in evolution are defined through a new notion of accessibility in phenotype space that provides a basis for straight forward interpretation of computer simulations on RNA optimization; furthermore, it reveals the constructive role of random genomic drift in the search for phenotypes of higher fitness. The effects of population size on the course of evolutionary optimization can be predicted quantitatively by means of a simple stochastic model based on a birth-anddeath process with immigration.

Base Sequence↗
PubMed1994

The prognosis and outcome of alcoholic liver disease.

Alcoholic liver disease evolves from fatty change through alcoholic hepatitis to alcoholic cirrhosis. Its development is associated with an excess mortality both in relation to the presence of liver disease and to other complications of alcohol abuse. In the majority of patients fatty liver is a benign lesion which will reverse completely following abstinence from alcohol. Continued drinking is associated with the eventual development of cirrhosis in approximately 20% of individuals. Survival rates of 70% are reported both at 2 years and at 10 years. Alcoholic hepatitis is a precirrhotic lesion; progression to cirrhosis is observed more commonly in women, in individuals with severe disease and in those who continue to drink. Thirty-day mortality rates of less than 20% are observed in patients with mild to moderate disease but exceed 40% in individuals with severe liver injury. Corticosteroids may improve short term survival in a small subgroup of patients with severe alcoholic hepatitis. Survival rates of 55 to 60% are reported both at 2 years and at 10 years. Survival is significantly reduced in women and in the elderly and is adversely affected by the presence of severe liver injury, evolution to cirrhosis and continued drinking. Two-thirds of patients with alcoholic cirrhosis present with decompensated disease; 15% will develop hepatocellular carcinoma. Survival rates at 5 years vary from zero to 80%; 60 to 90% of individuals die of their liver disease. Survival is adversely affected by the presence of decompensated disease, superimposed alcoholic hepatitis, continued drinking and the development of hepatocellular carcinoma. The advent of hepatic transplantation, which has a 5-year survival rate in excess of 70%, will influence these survival figures.

Carcinoma, Hepatocellular↗
PubMed2003

HIV biological variability unveiled: frequent isolations and chimeric receptors reveal unprecedented variation of coreceptor use.

OBJECTIVE: To follow the evolution of coreceptor use in HIV-1-infected individuals with varying rates of disease progression. METHODS: The coreceptor use of 278 sequential HIV-1 isolates from 23 individuals was tested by infection of two human cell lines, U87.CD4 and GHOST(3), expressing CD4 and CCR1, CCR2b, CCR3, CCR5, CXCR4, CXCR6 or BOB. Differences in coreceptor use were further dissected by testing chimeric coreceptors constructed by exchanging successively larger parts of CCR5 for corresponding regions of CXCR4. RESULTS: Three patterns of coreceptor use were distinguished: no evolution, evolution to CXCR4 use, and fluctuation. No evolution with stable CCR5 use (R5 phenotype) was linked to slow progression over 8-10 years in four patients. CXCR4-using virus was present from the onset (five patients) or appeared during clinical progression in all other patients, while taking zidovudine or didanosine monotherapy. The fluctuating pattern of coreceptor use, defined as reappearance of virus with R5 phenotype, was observed in five patients and, interestingly, followed initiation of highly active antiretroviral therapy in three of these. Monotropic R5 or X4 viruses were more selective in chimeric receptor use than R5X4 or multitropic viruses. Most importantly, the efficiency of chimeric receptor use increased over time. CONCLUSION: The increase in efficiency of chimeric receptor use allows a new interpretation of evolution of HIV-1 coreceptor use. Evolution could be a continuous process that may lead to changes in the way a coreceptor is used, with the potential of profound alteration in signalling at that receptor.

Adult↗
PubMed1993

Structured interviews for assessing children.

Structured interviews provide a valuable means of obtaining and quantifying information about the mental status of children. This review indicates that children can reliably self-report and that the information they provide can concur with the opinion of adults knowledgeable about them. However, considerably more research is warranted before it may be assumed that these interviews are adequately reliable and valid. In general, it appears that the task of documenting the psychometric soundness of these interviews has not been taken seriously, as if content validity were sufficient. For example, except for the CAS and the DISC, there has been little effort to study contrast group validity (i.e. whether the interview even differentiates "known groups"). More specifically, review of the reliability and validity data relevant to DSM-III-R diagnoses provides support for the CAS, DICA, ISC and K-SADS, with the validity data for the DICA being weaker than for the others. One limitation of these data for the DICA, ISC and K-SADS is that the diagnoses were clinician-generated, rather than algorithm-generated. Unfortunately the processes for generating clinical diagnoses were not specified, except for criterion reference to DSM-III-R. The findings for the DISC and the DISC-R are notably weak. There is no evidence for DISC reliability, except for adolescents, and the validity studies have demonstrated only weak relationships. There has been limited study of the psychometric properties of symptom scales. In fact, for two interviews (i.e. DICA and ISC), there are no data available. Reliability for the DISC scales is adequate only for adolescents. Psychometric data have been generated for the CAS and the K-SADS, with considerably more studies conducted with the CAS. The relative paucity of interest in scale scores is striking given that they provide a continuous variable which can indicate extent of symptoms. Other measures of mental status, besides presence/absence of diagnosis, will become increasingly important as research in child psychopathology progresses toward more sophisticated studies (i.e. treatment effects, risk factors). These interviews are labor intensive and costly to the researcher as well as time-consuming and tedious for the children and parents. Given this commitment, researchers should invest in developing other ways of exploiting the richness of the data generated. An example is the CAS "content" scales, which generate scores reflecting on the child's functioning in various areas (e.g. school, friends, family). As the evolution of these interviews continues, it will be important to remain attentive to the developmental limitations of children.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1994

Species-specific amplification of tRNA-derived short interspersed repetitive elements (SINEs) by retroposition: a process of parasitization of entire genomes during the evolution of salmonids.

Fourteen members of the Hpa I subfamilies of tRNA-derived SINEs in particular salmonid species were isolated from genomic libraries of chum salmon, kokanee, coho salmon, masu salmon, and steelhead. Alignment of the sequences of these 14 members, together with those of 4 members already published, 3 of which were previously demonstrated to have been amplified specifically in certain lineages, revealed the presence of five subfamilies with particular diagnostic nucleotides. The amplification of members of the same subfamily in different salmonid lineages and the amplification of members of different subfamilies in the same salmonid lineage suggest that multiple dispersed loci were responsible for amplification or, alternatively, that SINEs were transmitted horizontally between species. These two possibilities are not mutually exclusive. Our results also indicate that the Hpa I SINEs in salmonids behave like parasites. The amplification of these SINEs is ongoing and continues to shape the evolution of salmonid genomes.

Animals↗
PubMedDate not supplied

Repair-modification and evolution of the eukaryotic genome organization.

For a complete reconstruction of the damaged unmethylated islands, in theory, the conventional excision-repair is sufficient. For a complete reconstruction of the damaged methylated domains, a coupling has to take place involving the excision-repair (able to reestablish their ATGC-language) plus the DNA-methylase (able to reestablish their modified ATGC5mC-language). This coupling, defined as "repair-modification," is essentially functioning during the S-phase, because the DNA-polymerase beta (pol beta) is active during the whole cell cycle, whereas the DNA-methylase (met) is active in S and appears to be repressed or inactive during the major part of G1 and during the phases G2 and M. Consequently, after damage, some silent genes might become expressed during these phases, if it is true that DNA methylation is inversely proportional to transcription. Repair-modification should, therefore, exert a continuous differential pressure on evolution of given parts of the genome, when they are methylated to a different extent. According to Darwinian concepts, repair-modification would lead to a high variability, especially of uncoding DNA sequences (if hypermethylated), whereas on the basis of this variability, selection might favor transposition of specific regulatory elements into given transcriptional units. In these, the conservative nature of the coding elements (if unmethylated) would obviously be ensured by the conventional excision-repair.

Animals↗
PubMedDate not supplied

Comparison of metabolic abnormalities and clinical lipodystrophy 48 weeks after switching from HAART to Trizivir versus continued HAART: the Trizal study.

PURPOSE: To analyze the evolution of clinical lipodystrophy (LD) and metabolic abnormalities in patients continuing to receive HAART versus patients switched to Trizivir (zidovudine, lamivudine, abacavir) after 48 weeks. METHOD: Patients treated with HAART >6 months with plasma HIV-1 RNA viral load (VL) <400 copies/mL and <50 copies/mL at screening were randomly assigned to continue HAART (103 patients) or to receive Trizivir (106 patients). Clinical LD was evaluated using a standardized patient questionnaire only at baseline, weeks 4 and 8, and then every 8 weeks until Week 48. Laboratory evaluation was performed every 4 weeks. RESULTS: The proportion of patients exhibiting >or=1 LD symptom at baseline was 40% in the Trizivir arm and 50% in HAART arm (difference not significant). After 48 weeks, the prevalence was 28% and 42% respectively (p =.03), and the median number of LD symptoms per patient was 2 in the Trizivir arm and 4 in the continued HAART arm (p =.016). Median decreases in cholesterol levels over the 48-week study period were greater in the Trizivir arm than in the continued HAART arm (-0.80 vs. -0.44 mmol/L; p lt.001). Median triglyceride levels decreased in the Trizivir arm but increased in the continued HAART arm (-0.17 and +0.01 mmol/L; p =.006). Suppression of VL was maintained in most patients with no differences between the two arms. CONCLUSION: A switch from "standard" HAART to Trizivir was associated with an improvement in clinical LD and blood lipid abnormalities after 48 weeks.

Adult↗
PubMedDate not supplied

Relationships between specialized cells, capillaries and intermediary cytofibrillary elements. XVIIth Note. Biological evolution of the respiratory subsystem in Reptilia.

This note continues the XIIth, XVth and XVIth ones concerning the biological evolution of the respiratory subsystem (SS.Rs.) in invertebrates, aquatic vertebrates and amphibians. Author tries to discern some of the factors involved in the passage from Amphibia to Reptilia. The lengthy evolution of embryotrophic mechanisms during this process in the light of the aromorphotic theory (A. N. Sewertsow) and the accelerating form of dyschronism (De Beer) are highlighted. The result of these changes is the formation of a large telolecithal egg endowed with all the embryotrophic reserves needed for the terrestrial evolution, for its acceleration and condensation, through the suppression of the larval stage and of metamorphosis, as well as through the appearance of some new characters. The evolution of the extraembryonic area in Amniota precursors and in Amniota and their homeothermal descendants, both oviparous and viviparous, is also discussed. The succession of respiratory organs is followed up (yolk sac, external branchiae, allantois, placenta) in the light of the organ substitution theory and of the biological stereo-type theory (Mârza, Repciuc, Eskenasy).

Animals↗
PubMed1982

Life support system development in West Germany.

The delivery of fully qualified Environmental Control and Life Support System (ECLS) flight hardware for the Spacelab Flight Unit was completed in 1979, and the first Spacelab flight is scheduled for mid 1983. With Spacelab approaching its operational stage, ESA has initiated the Follow-on Development Programme. The future evolution of Spacelab elements in a continued U.S./European cooperation is obviously linked to the U.S. STS evolution and leads from the sortie-mode improvements (Initial Step) towards pallet systems and module applications in unmanned and manned space platforms (Medium and Far Term Alternatives). Extensive studies and design work have been accomplished on life support systems for Life Sciences Laboratories (Biorack) in Spacelab (incubators and holding units for low vertebrates). Future long term missions require the implementation of closed loop life support systems and in order to meet the long range development cycle feasibility studies have been performed. Terrestrial applications of the life support technologies developed for space have been successfully implemented.

Animals↗
PubMed1978

[Progressive enlargement and thrombosis of an anterior communicating artery aneurysm. Clinical, radiological and histological study (author's transl)].

A non operated aneurysm of the anterior communicating artery enlarged considerably over a seven years period; it finally thrombosed and behaved like a suprasellar tumor. The clinical course, the angiographic evolution and the anatomical examination allowed, in this case, to account for the increase in volume by progressive stretching of the wall, and not by incorporation of a false aneurysmal sack resulting from an encapsulated haematoma. Histologically, the wall of this giant aneurysm showed various changes : on the inner aspect, progressive thickening occurs, due to fibrous organization of mural thrombosis; in the depth, far from the nutrient sources, necrotic atheromatous like foci occur, which isolate an inner leaflet, prone to become nectrotic at a later stage. Distension of such a weakened wall may lead to several consequences; a progressive increase in volume of the aneurysm, partial ruptures with haemodissection starting from the aneurysmal lumen, or even complete rupture of the wall and subarachnoid haemorrhage. On the other hand, circulatory stasis, due to the important increase in volume, may facilitate progressive thrombosis of the aneurysm. The living character of the wall is emphasized by the coexistance of these unfavourable (degeneration, ruptures) and favourable (thrombosis, fibrous organization) features, which continuously influence the spontaneous evolution of the aneurysm.

Cerebral Arteries↗
PubMed2004

Associative nitrogen fixation, C4 photosynthesis, and the evolution of spittlebugs (Hemiptera: Cercopidae) as major pests of neotropical sugarcane and forage grasses.

Neotropical grass-feeding spittlebugs of several genera are important pests of pasture grasses from the southeastern USA to northern Argentina, and of sugarcane from southern Mexico to southern Brazil, causing estimated reductions of up to 70% in yield and estimated monetary losses of 840-2100 million US dollars annually. With few exceptions, the species badly damaged by these spittlebugs are introduced C4 grasses that exhibit associative nitrogen fixation. This study synthesizes evidence that the pest status of many tropical and subtropical grass-feeding spittlebugs is linked to associative N-fixation in their C4 hosts. Recognition that associative N-fixation is a major factor in spittlebug host preferences should deepen understanding of spittlebug agricultural ecology and facilitate efforts to combat spittlebug pests. In particular, spittlebugs should be susceptible to manipulation of xylem transport solutes. However, reduction of nitrate fertilizer rates, increase in ammonium fertilizer rates, or enhancement of associative N-fixation as a consequence of genetic engineering could make hosts more susceptible to spittlebug attack. Because of their predilection for C4 grasses, spittlebugs present a clear counterexample to the hypothesis that herbivores prefer C3 plants to C4 plants. Finally, it appears that declines in atmospheric carbon dioxide levels during recent geological history promoted the proliferation of C4 grasses. This, compounded by human agricultural activities, has driven an ecological and evolutionary radiation of grass-feeding spittlebugs that presents continuing opportunities for the evolution of spittlebug pests.

Animals↗
PubMed1996

Escape and migration of nucleic acids between chloroplasts, mitochondria, and the nucleus.

The escape and migration of genetic information between mitochondria, chloroplasts, and nuclei have been an integral part of evolution and has a continuing impact on the biology of cells. The evolutionary transfer of functional genes and fragments of genes from chloroplasts to mitochondria, from chloroplasts to nuclei, and from mitochondria to nuclei has been documented for numerous organisms. Most documented instances of genetic material transfer have involved the transfer of information from mitochondria and chloroplasts to the nucleus. The pathways for the escape of DNA from organelles may include transient breaches in organellar membranes during fusion and/or budding processes, terminal degradation of organelles by autophagy coupled with the subsequent release of nucleic acids to the cytoplasm, illicit use of nucleic acid or protein import machinery, or fusion between heterotypic membranes. Some or all of these pathways may lead to the escape of DNA or RNA from organellar compartments with subsequent uptake of nucleic acids from the cytoplasm into the nucleus. Investigations into the escape of DNA from mitochondria in yeast have shown the rate of escape for gene-sized fragments of DNA from mitochondria and its subsequent migration to the nucleus to be roughly equivalent to the rate of spontaneous mutation of nuclear genes. Smaller fragments of mitochondrial DNA may appear in the nucleus even more frequently. Mutations of nuclear genes that define gene products important in controlling the rate of DNA escape from mitochondria in yeast also have been described. The escape of genetic material from mitochondria and chloroplasts has clearly had an impact on nuclear genetic organization throughout evolution and may also affect cellular metabolic processes.

Animals↗
PubMed1997

A molecular predator and its prey: coupled isothermal amplification of nucleic acids.

BACKGROUND: A novel approach to the study of in vitro evolution is provided by the investigation of continuous, functionally coupled, amplifying systems. To date, in vitro evolution experiments have focused on issues of mutation and selection. Our work contributes to the new field of in vitro molecular ecology studies in which detailed information about the relationship between sequence changes and molecular interactions is obtained. Predator-prey systems are interesting in this context both in terms of evolutionary limits and in terms of the potential kinetic properties of oscillation and spatial pattern formation. Such molecular predator-prey models can be extended to a further negative-interaction mode, viral-host molecular evolution. RESULTS: A simple, nonfunctional predator-prey system based on the self-sustained sequence replication reaction is proposed. Coupling within the system is achieved using the single-stranded DNA intermediate of one cycle, the prey cycle, as primer for the second one, the predator cycle. Hybridization by complementary base pairing is the second order reaction step underlying the predation. Single steps of the whole reaction system have been investigated by radiolabeling. Each isolated subsystem operates according to the proposed reaction scheme, and evidence for an efficient coupling of both subsystems according to the proposed mechanism was found. CONCLUSIONS: Simple, interacting model systems based on nucleic acids can be designed and constructed for the study of coevolution. The results of studies such as the one described here will provide a basis for the construction of coupled systems of ribozymes, from which point the engineering of catalytic units for applications in biotechnology is feasible.

Base Sequence↗
PubMed1991

Gastrointestinal endoscopy and general surgical practice. Surgical endoscopy versus surgeon endoscopists.

Endoscopic studies and treatment are a necessary and vital component of General Surgery practice. Since most of the concepts related to therapeutic endoscopy were conceived and developed in the context of surgical science, it is both appropriate and necessary that surgeons continue their involvement with this modality. Furthermore, within the evolution of surgical science, endoscopic tools will continue to be utilized.

Digestive System↗
PubMed2025

Cross-Kingdom Genomic Conservation of Putative Human Sleep-Related Genes: Phylogenomic Evidence From Chlamydomonas reinhardtii.

Sleep is a widespread and evolutionarily conserved process observed in diverse organisms, from jellyfish to mammals, hinting at its origin as a life-supporting mechanism over 500 million years ago. Although its fundamental purpose and mechanisms remain unclear, sleep's evolution and adaptive significance continue to be debated. This study explores the evolutionary origins of sleep using Chlamydomonas reinhardtii as a model organism, identifying 112 putative sleep-related genes across species and highlighting the evolutionary conservation of sleep-regulatory pathways. Additionally, discovering uncharacterized proteins with high sequence similarity and significant e-values suggests unexplored roles in sleep regulation, underscoring the potential of C. reinhardtii to reveal new insights into the molecular basis of sleep. This study provides a foundation for identifying previously unknown sleep-associated proteins, particularly within single-celled organisms, which may offer novel perspectives on the biological role of sleep. The study demonstrates that phylogenomic analysis of diverse model organisms can expand our understanding of the evolutionary trajectory of sleep and its fundamental function, paving the way for further research in sleep biology and its health implications. Overall, the fundamental functions of sleep observed in higher animal phyla originated from its primordial activities, demonstrating an evolutionary continuum wherein more specialized tasks were integrated with sleep's essential restorative properties.

Chlamydomonas reinhardtii↗
PubMed2005

[Euthanasia in patients with cancer and the continuous-care providers].

During the clinical evolution of patients with cancer there are many occasions, or phases of the disease, when there are no specific treatments and, as such, we need to provide maximum comfort following appropriate symptom control; in this stage it is fundamental to respect personal autonomy together with the option to reject futile treatment. With appropriate control of symptoms it is possible to reach the stage where the majority of the patients do not continue to suffer. Continuous-care providers for cancer patients are those who are responsible for providing help to resolve these situations. In palliative medicine there are highly-efficacious procedures to the help in these last hours. Sedation is applied when it is impossible to control symptoms by other means. With appropriate Carer cover, it is not necessary to introduce laws on assisted suicide and/or active voluntary euthanasia, neither because of the magnitude of demand, nor because of the difficulties in achieving appropriate control of symptoms.

Australia↗
PubMed2002

The human endogenous retrovirus family HERV-K(HML-3).

A substantial amount of the human genome is composed of human endogenous retroviruses (HERVs). Manifold HERV families have been identified, among them several so-called HERV-K(HML) families. Although the HERV-K(HML-2) family has been studied in detail, other HERV-K families are not as well characterized. We describe here the HERV-K HML-3 family in more detail. We estimate that there are about 140 proviral loci or remains of such per haploid genome. Most loci are severely mutated. Proviruses displaying larger deletions in gag and pol are common. A multiple alignment of 73 HERV-K(HML-3) sequences displays several potentially important differences compared with the HERVK9I sequence in Repbase. A consensus sequence with open reading frames for all retroviral genes was generated, for which intact dUTPase motifs and env gene variants with different coding capacities are observed. Phylogenetic analysis shows near-monophyly with distinction of two closely related subgroups. Proviruses formed about 36 million years ago. However, no continuous activity through primate evolution is indicated.

Base Sequence↗