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At least 1,207 records · Page 67Linked to original sources
PubMed1997

Properties of interictal discharges induced by hippocampal kindling.

The present experiment was designed to reveal the characteristics of interictal discharges (IIDs) induced by kindling of the rabbit hippocampus. Out of 21 animals, 13 developed stage 5 convulsions with a mean of 18 stimulations (Kindled (K) group), whereas the remaining eight animals did not (incomplete kindling (IK) group). A correlation between the duration of the afterdischarge and the behavioral stages was found in the K group. However, changes in frequency of total IIDs during kindling did not differ between the two groups. In the acute experiments performed after kindling, IIDs were classified into two types: simple and complex IIDs. The former was further classified into two subtypes (A and B) according to the laminar profile in the CA1 region. The A type of simple IIDs showed a negative polarity in the apical dendritic layer, while the B type showed a negative polarity in the basal dendritic layer. Complex IIDs basically consisted of two to three simple IIDs and were often followed by large irregular activity. Retrospective analysis was done, based on the classification of IIDs in the acute experiments (n = 12). Consequently, in the K group (n = 7), the frequency of complex IIDs rather than that of simple ones was closely related to the enhancement of behavioral responses during kindling. On the other hand, in the IK group (n = 5), simple IIDs occurred at a higher frequency, and did not parallel the changes in seizure behavior. It is concluded that complex IIDs play an important role in the propagation as well as the evolution of kindling effects.

Animals↗
PubMed1982

Calcium-dependent alpha-helical structure in osteocalcin.

Osteocalcin is an abundant Ca2+-binding protein of bone containing three residues of vitamin K dependent gamma-carboxyglutamic acid (Gla) among its 49 (human, monkey, cow) or 50 (chicken) amino acids. Gla side chains participate directly in the binding of Ca2+ ions and the adsorption of osteocalcin to hydroxylapatite (HA) surfaces in vivo and in vitro. Osteocalcin exhibits a major conformational change when Ca2+ is bound. Metal-free chicken osteocalcin is a random coil with only 8% of its residues in the alpha helix as revealed by circular dichroism. In the presence of physiological levels of Ca2+, 38% of the protein adopts the alpha-helical conformation with a transition midpoint at 0.75 mM Ca2+ in a rapid, reversible fashion which (1) requires an intact disulfide bridge, (2) is proportionally diminished when Gla residues are decarboxylated to Glu, (3) is insensitive to 1.5 m NaCl, and (4) can be mimicked by other cations. Tyr fluorescence, UV difference spectra, and Tyr reactivity to tetranitromethane corroborate the conformational change. Homologous monkey osteocalcin also exhibits Ca2+-dependent structure. Integration of predictive calculations from osteocalcin sequence has yielded a structural model for the protein, the dominant features of which include two opposing alpha-helical domains of 9-12 residues each, connected by a bea turn and stabilized by the Cys23-Cys29 disulfide bond. Cation binding permits realization of the full alph a-helical potential by partial neutralization of high anionic charge in the helical domains. Periodic Gla occurrence at positions 17, 21, and 24 has been strongly conserved throughout evolution and places all Gla side chains on the same face of one alpha helix spaced at intervals of approximately 5.4 A, closely paralleling the interatomic separation of Ca2+ in the HA lattice. Helical osteocalcin has greatly increased affinity for HA; thus, the Ca2+-induced structural transition may perform an informational role related to bone metabolism.

1-Carboxyglutamic Acid↗
PubMed2001

Extreme morphological and ecological homoplasy in tropical salamanders.

Fossorial salamanders typically have elongate and attenuated heads and bodies, diminutive limbs, hands and feet, and extremely elongate tails. Batrachoseps from California, Lineatriton from eastern México, and Oedipina from southern México to Ecuador, all members of the family Plethodontidae, tribe Bolitoglossini, resemble one another in external morphology, which has evolved independently. Whereas Oedipina and Batrachoseps are elongate because there are more trunk vertebrae, a widespread homoplasy (parallelism) in salamanders, the genus Lineatriton is unique in having evolved convergently by an alternate "giraffe-neck" developmental program. Lineatriton has the same number of trunk vertebrae as related, nonelongated taxa, but individual trunk vertebrae are elongated. A robust phylogenetic hypothesis, based on sequences of three mtDNA genes, finds Lineatriton to be deeply nested within a clade characterized by generalized ecology and morphology. Lineatriton lineolus, the only currently recognized taxon in the genus, shows unanticipated genetic diversity. Surprisingly, geographically separated populations of L. lineolus are not monophyletic, but are sister taxa of different species of the morphologically generalized genus Pseudoeurycea. Lineatriton, long thought to be a unique monospecific lineage, is polyphyletic. Accordingly, the specialized morphology of Lineatriton displays homoplasy at two hierarchical levels: (i) with respect to other elongate lineages in the family (convergence), and (ii) within what is currently recognized as a single taxon (parallelism). These evolutionary events are of adaptive significance because to invade the lowland tropics salamanders must be either arboreal or fossorial; the repeated evolution of elongation and attenuation has led to multiple lowland invasions.

Animals↗
PubMed1983

Purification and characterization of two ribosomal proteins of Saccharomyces cerevisiae. Homologies with proteins from eukaryotic species and with bacterial protein EC L11.

Two non-acidic proteins, extracted from the ribosomes of Saccharomyces cerevisiae using 1 M ammonium chloride in the presence of 50% ethanol, have been purified and characterized. Similar proteins are present in other eukaryotic ribosomes tested, as determined by two-dimensional gel electrophoresis and cross-reaction with antisera. One of the two yeast proteins, protein YL23, seems to be very well preserved during evolution, since antisera specific for YL23 cross-react with protein EC L11 from Escherichia coli. The structural similarity between these two proteins parallels a functional equivalence shown by the ability of the bacterial protein to reconstitute the activity of protein-deficient core particles from yeast. However, in contrast to protein EC L11, protein YL23 interacts with the yeast acidic proteins, forming a complex probably similar to the one made by bacterial protein EC L10 with proteins EC L7 and EC L12 in the E. coli ribosome. Protein YL23 might play similar roles to those of proteins EC L10 and EC L11 in bacteria.

Animals↗
PubMed2004

Drug resistance, virus fitness and HIV-1 mutagenesis.

The evolution of antiretroviral drug resistance is a major problem in the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Drug therapy failure is associated with accumulation of drug resistance mutations and results in the development of drug resistance. Drugs targeted against reverse transcriptase (RT) as well as drug-resistant RT have been shown to increase HIV-1 mutation frequencies. Furthermore, combinations of drug and drug-resistant RT can increase virus mutation frequencies in a multiplicative manner. The evolution of drug resistance also alters virus fitness. The correlation of increased HIV-1 mutation rates with the evolution of antiretroviral drug resistance indicates that drug failure could increase the likelihood of further resistance evolving from subsequent drug regimens. These observations parallel studies from microbial systems that provide evidence for a correlation between drug resistance development and increased pathogen mutation rates. Although increased mutant frequencies may be detrimental to effective therapy, the lethal mutagenesis of the HIV-1 genome may provide a new means for antiretroviral therapy.

Animals↗
PubMed1977

Temperature relations of aerial and aquatic respiration in six littoral snails in respiration in six littoral snails in relation to their vertical zonation.

Aerial and aquatic rates of oxygen consumption were determined over a range of 5 degrees to 45 degrees C at 5 degrees C intervals for six species of marine littoral snails: including the sublittoral species, Acmaea testudinalis, Mitrella lunata, and Lacuna vincta; and the truly intertidal species, Littorina obtusata, L. littorea, and L. saxatilis. Polarographic oxygen electrodes were used with normally active snails collected from populations on Nobska and Manomet Points, Massachusetts. Three subtidal species, A. testudinalis, Lacuna vincta, and M. lunata, do not display any metabolic adjustment to increasing temperature, with thermal limits reached at 30 degrees to 35 degrees C. Aerial respiration in A. testudinalis is similar to aquatic O2 uptake, but rates average only 36.4% of aquatic rates. The intertidal congeners, Littorina obtusata, L. littorea and L. saxatilis, have varying degrees of aerial and aquatic metabolic regulation with increasing temperature. L. obtusata, a low intertidal snail exposed to air for 15% to 45% of the tidal cycle, displays a respiratory pattern of "passive endurance" to high temperatures both in air and in water. L. littorea, the dominant snail of the midlittoral region, remains active when exposed to air (30% to 75% of the tidal cycle) and has a zone of metabolic regulation between 20 degrees C and 30 degrees C. Over this, the normal ambient temperature range, the Q10 closely approximates one, and nearly equivalent O2 uptake rates occur in air and in water. L. saxatilis from the upper littoral region is exposed to air for 70% to 95% of the tidal cycle and is characterized by reduced aerial and aquatic O2 uptake rates above 25 degrees C, representing a reversible torpor up to its thermal maximum at 44 degrees C. For these six snail species, respiratory responses to increasing temperature are thus directly related to the pattern of vertical distribution in the intertidal environment. Discussion of this relationship stresses that the evolution of other nearterrestrial structures and functions in littoral snails has proceeded in a discontinuous fashion. Despite this, the temperature responses in respiration parallel the functional morphology of the pallial structures and the physiological patterns of response to low oxygen stress, as well as adaptive features of reproduction, larval development, water-control, and nitrogenous excretion.

Acclimatization↗
PubMed2005

HIV-1 mutagenesis during antiretroviral therapy: implications for successful drug treatment.

The evolution of antiretroviral drug resistance is a major problem in the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Drug therapy failure is associated with accumulation of mutations and results in the development of drug resistance. Drugs targeted against reverse transcriptase (RT) as well as drug-resistant RT have been shown to increase HIV-1 mutation frequencies. Furthermore, combinations of drug and drug-resistant RT can increase virus mutation frequencies in a multiplicative manner. The evolution of drug resistance also alters virus fitness. The correlation of increased HIV-1 mutation rates with the evolution of antiretroviral drug resistance indicates that drug failure could increase the likelihood of further resistance evolving from subsequent drug regimens. These observations parallel studies from microbial systems that provide evidence for a correlation between drug resistance development and increased pathogen mutation rates. Although increased mutant frequencies may be detrimental to effective therapy, the lethal mutagenesis of the HIV-1 genome may provide a new means for antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed2002

[Method for measuring dental roots by roentgenograms for making experimental models].

Two methods were used for measuring the true size of abutment teeth roots for making experimental models. One method was based on the use of intraoral contact roentgenograms made with a Russian 5D-2 x-ray diagnostic dental device and the other on the use of roentgenograms made with parallel beam bundles from a longer distance using an x-ray diagnostic dental device with a more potent x-ray tube, Evolution-300 (Italy) on a Kodak x-ray film (USA) Ultra-speed-58, 3.1[symbol: see text]4.1 cm. The results obtained by the latter method are more accurate, the difference from the true size being no more than 0.5 mm. However intraoral contact roentgenograms give the results close to the true size of abutment teeth roots, for example, for one of the mandibular premolars; however a correction coefficient should be used.

Dental Abutments↗
PubMed2003

It's time to rework the blueprints: building a science for clinical psychology.

The aims in this article are to connect the conceptual structure of clinical psychological science to what the author believes to be the omnipresent principles of evolution, use the evolutionary model to create a deductively derived clinical theory and taxonomy, link the theory and taxonomy to comprehensive and integrated approaches to assessment, and outline a framework for an integrative synergistic model of psychotherapy. These foundations also provide a framework for a systematic approach to the subject realms of personology and psychopathology. Exploring nature's deep principles, the model revives the personologic concept christened by Henry Murray some 65 years ago; it also parallels the interface between human social functioning and evolutionary biology proposed by Edward Wilson in his concept of sociobiology.

Biological Evolution↗
PubMed2001

Structural constraints and emergence of sequence patterns in protein evolution.

The aim of this work was to study the relationship between structure conservation and sequence divergence in protein evolution. To this end, we developed a model of structurally constrained protein evolution (SCPE) in which trial sequences, generated by random mutations at gene level, are selected against departure from a reference three-dimensional structure. Since at the mutational level SCPE is completely unbiased, any emergent sequence pattern will be due exclusively to structural constraints. In this first report, it is shown that SCPE correctly predicts the characteristic hexapeptide motif of the left-handed parallel beta helix (LbetaH) domain of UDP-N-acetylglucosamine acyltransferases (LpxA).

Acyltransferases↗
PubMed2006

Sexual reproduction and the evolution of microbial pathogens.

Three common systemic human fungal pathogens--Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus--have retained all the machinery to engage in sexual reproduction, and yet their populations are often clonal with limited evidence for recombination. Striking parallels have emerged with four protozoan parasites that infect humans: Toxoplasma gondii, Trypanosoma brucei, Trypanosoma cruzi and Plasmodium falciparum. Limiting sexual reproduction appears to be a common virulence strategy, enabling generation of clonal populations well adapted to host and environmental niches, yet retaining the ability to engage in sexual or parasexual reproduction and respond to selective pressure. Continued investigation of the sexual nature of microbial pathogens should facilitate both laboratory investigation and an understanding of the complex interplay between pathogens, hosts, vectors, and their environments.

Animals↗
PubMed1996

Excessive homoplasy in an evolutionarily constrained protein.

The evolution of monomorphic proteins among closely related species has not been examined in detail. To investigate this phenomenon, the glycerol-3-phosphate dehydrogenase (Gpdh) locus was sequence in a broad range of Drosophila species. Although purifying selection to remove amino acid variation is the dominant force in the evolution of Gpdh, some replacements have occurred. The sequences were compared in the context of the phylogeny of the genus, revealing a high proportion of amino acid parallelism and reversal (homoplasy) at four sites. The level of homoplasy is significantly greater than that seen in other proteins for which multiple sequences are available, showing that Gpdh is strongly constrained by both the number of amino acid differences and the types of changes allowed. These four sites evolve at a much higher rate than do the other variable positions in the protein, accounting for half of the interspecific amino acid replacements. However, unlike typical hypervariable sites, where multiple changes to several different amino acids are seen, evolutionary 'flip-flopping' between two amino acid states defines this new class of hypervariable site.

Amino Acid Sequence↗
PubMed1975

Sulfur dioxide inhibition of photosynthesis in isolated spinach chloroplasts.

Photosynthetic oxygen evolution by isolated spinach (Spinacia oleracea L.) chloroplasts approached complete inhibition in the presence of a 5 mm concentration of sulfur dioxide. A similar inhibition was observed in the presence of equimolar concentrations of bisulfite ions, suggesting a parallel mode of action. In contrast, an equimolar concentration of sulfite ions was markedly less inhibitory and sulfate ions caused negligible inhibition of apparent photosynthesis. The mode of action of sulfur dioxide and related sulfur anions in inhibiting photosynthesis was found to be essentially independent of direct hydrogen-ion effects. Supplements of inorganic pyrophosphate lessened the inhibition of oxygen evolution caused by sulfur dioxide and the sulfur anions.Sulfur dioxide and the sulfur anions were almost equally effective in inhibiting cyclic and noncyclic photophosphorylation in chloroplast suspensions. However, the extent of the inhibition of these photosynthetic reactions does not appear sufficient to account for the inhibition of photosynthetic oxygen evolution by sulfur dioxide.

Journal Article↗
PubMed1981

Microtubule turnover as a mechanism of mitosis and its possible evolution.

Movement of chromosomes during mitosis appears to be coupled to the unidirectional turnover of spindle microtubules. This paper outlines a directional turnover model of mitosis which hypothesizes that: (1) Unidirectional turnover of tubulin subunits and microtubule-associated proteins occurs from an assembly site at one end to a disassembly site at the other end of mitotic apparatus microtubules. (2) The components of interpolar microtubules are continuously moving toward each pole due to their assembly in the opposite half spindle and disassembly in the near half spindle. (3) Mitotic chromosome movements are coupled to this directional turnover by selective formation of semi-stable lateral interactions or bridges between kinetochore microtubules and parallel interpolar microtubules. (4) The anaphase velocity of kinetochores relative to the poles is determined by the rate that kinetochore microtubules disassemble on their poleward ends minus the rate they assemble at their kinetochore ends. (5) Spindle elongation occurs when assembly of interpolar microtubules is more rapid than their disassembly or when interpolar microtubules slide in an anti-parallel arrangement. (6) The velocity of chromosome separation is the sum of spindle elongation and the poleward movements of sister chromosomes. Evidence for and against these hypotheses and some possible steps in the evolution of this type of mechanism are discussed.

Animals↗
PubMed2000

Permanence or change? The meaning of genetic variation.

Selected aspects of the evolutionary process and more specifically of the genetic variation are considered, with an emphasis in studies performed by my group. One key aspect of evolution seems to be the concomitant occurrence of dichotomic, contradictory (dialect) processes. Genetic variation is structured, and the dynamics of change at one level is not necessarily paralleled by that in another. The pathogenesis-related protein superfamily can be cited as an example in which permanence (the maintenance of certain key genetic features) coexists with change (modifications that led to different functions in different classes of organisms). Relationships between structure and function are exemplified by studies with hemoglobin Porto Alegre. The genetic structure of tribal populations may differ in important aspects from that of industrialized societies. Evolutionary histories also may differ when considered through the investigation of patrilineal or matrilineal lineages. Global evaluations taking into consideration all of these aspects are needed if we really want to understand the meaning of genetic variation.

Africa↗
PubMed1975

The place of the australopithecines in human evolution: grounds for doubt?

Although most studies emphasise the similarity of the australopithecines to modern man, and suggest, therefore, that these creatures were bipedal tool-makers at least one form of which (Australopithecus africanus--"Homo habilis", "Homo africanus") was almost directly ancestral to man, a series of multivariate statistical studies of various postcranial fragments suggests other conclusions. Their locomotion may not have been like that of modern man, and may, though including a form or forms of bipedality, have been different enough to allow marked abilities for climbing. Bipedality may have arisen more than once, the Australopithecinae displaying one or more experiments in bipedality that failed. The genus Homo may, in fact, be so ancient as to parallel entirely the genus Australopithecus thus denying the latter a direct place in the human lineage.

Animals↗
PubMed2026

Regulatory Evolution and the Genetic Basis of Human Brain Expansion.

The evolution of the human brain is characterized by profound changes in structure and function, despite relatively limited divergence in protein-coding genes compared to other primates. This paradox has led to increasing recognition of gene regulatory elements (GREs) as primary drivers of evolutionary innovation. In this review, we synthesize current knowledge on the role of conserved noncoding elements (CNEs), human accelerated regions (HARs), and transposable element (TE)-derived sequences in shaping gene regulatory networks (GRNs) underlying brain development. Comparative analyses across humans and closely related primates, including the chimpanzee, gorilla, and orangutan, reveal that while core regulatory architectures are highly conserved, subtle changes in regulatory elements drive species-specific gene expression patterns. We highlight how CNEs provide a stable regulatory framework, whereas HARs and TE-derived elements introduce lineage-specific modifications that fine-tune neurodevelopmental processes. Advances in functional genomics, including CRISPR-based perturbations, massively parallel reporter assays, and single-cell multi-omics, have enabled direct interrogation of regulatory function, linking sequence variation to cellular phenotypes. Furthermore, we discuss how regulatory evolution contributes to both cognitive innovation and susceptibility to neurological disorders. Despite significant progress, challenges remain in establishing causal relationships between regulatory variation and phenotypic outcomes. Future integration of multi-omics data and comparative models will be essential for resolving these complexities. Together, this review provides a comprehensive framework for understanding the molecular basis of primate brain evolution through the lens of gene regulation.

Brain evolution↗
PubMed2004

Mutation exposed: a neutral explanation for extreme base composition of an endosymbiont genome.

The influence of neutral mutation pressure versus selection on base composition evolution is a subject of considerable controversy. Yet the present study represents the first explicit population genetic analysis of this issue in prokaryotes, the group in which base composition variation is most dramatic. Here, we explore the impact of mutation and selection on the dynamics of synonymous changes in Buchnera aphidicola, the AT-rich bacterial endosymbiont of aphids. Specifically, we evaluated three forms of evidence. (i) We compared the frequencies of directional base changes (AT-->GC vs. GC-->AT) at synonymous sites within and between Buchnera species, to test for selective preference versus effective neutrality of these mutational categories. Reconstructed mutational changes across a robust intraspecific phylogeny showed a nearly 1:1 AT-->GC:GC-->AT ratio. Likewise, stationarity of base composition among Buchnera species indicated equal rates of AT-->GC and GC-->AT substitutions. The similarity of these patterns within and between species supported the neutral model. (ii) We observed an equivalence of relative per-site AT mutation rate and current AT content at synonymous sites, indicating that base composition is at mutational equilibrium. (iii) We demonstrated statistically greater equality in the frequency of mutational categories in Buchnera than in parallel mammalian studies that documented selection on synonymous sites. Our results indicate that effectively neutral mutational pressure, rather than selection, represents the major force driving base composition evolution in Buchnera. Thus they further corroborate recent evidence for the critical role of reduced N(e) in the molecular evolution of bacterial endosymbionts.

Animals↗