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At least 1,351 records · Page 75Linked to original sources
PubMed1987

Resynchronization of the circadian system following a 9-hr advance or a delay zeitgeber shift: real flights and simulations by a Van-der-Pol oscillator.

After a flight from Germany to California, eight subjects stayed there for 3 weeks and then were flown back to Germany. After both the westbound and the eastbound flights, body temperature was measured for 2 weeks in the new time zone. Data obtained every 3 hr throughout the day and night were analyzed by the complex demodulation technique to visualize phase adjustments and the nonstationary amplitude of the measured circadian rhythms. The response to the zeitgeber delay was very similar in all subjects and consisted of a phase adjustment of 6 hr in the first 2 days following the flight and a subsequent slow completion of the resynchronization with a rate of 0.5 to 1 hr per day. After the eastbound flight the resynchronization was generally slower, and the circadian amplitudes were more reduced than after the zeitgeber delay. In addition, the advance shift led to different patterns of phase adjustment for the individuals. Shortening and lengthening of circadian periods as well as phase jumps by about 12 hr were observed. Simulations with a Van-der-Pol oscillator forced by a rectangular zeitgeber function clearly reflected the divergence in resynchronization between eastbound and westbound flights. The different resynchronization patterns found after the 9-hr zeitgeber advance, including the corresponding duration of readjustment, could also be well simulated.

Adaptation, Physiological↗
PubMed1994

Tetrapeptide tyrosine kinase inhibitors. Enantioselective synthesis of p-hydroxymethyl-L-phenylalanine, incorporation into a tetrapeptide, and subsequent elaboration into p-(R,S-hydroxyphosphonomethyl)-L-phenylalanine.

A convenient enantioselective synthesis of p-hydroxymethyl-L-phenylalanine was developed which produces a 4/1 ratio of L/D enantiomers resulting from a chiral phase-transfer-catalyzed alkylation. This amino acid was coupled into the p56(1)ck tyrosine kinase substrate Ac-Leu-Pro-Tyr-Ala-NHCH3 as a replacement for Tyr and can subsequently be elaborated into a variety of potential tyrosine kinase inhibitor designs of general structure Ac-Leu-Pro-AA-Ala-NHCH3, wherein AA is an unnatural amino acid. The contaminating D enantiomer was readily removed after coupling to L-Ala-NHCH3 of this sequence. The utility of the p-hydroxymethyl functionality in an efficient divergent synthetic strategy leading to various inhibitor designs is illustrated with the synthesis of Ac-Leu-Pro-AA-Ala-NHCH3, wherein AA is p-(R,S-hydroxyphosphonomethyl)-L-phenylalanine.

Amino Acid Sequence↗
PubMed1996

Opposing effects of the basic helix-loop-helix transcription factor SCL on erythroid and monocytic differentiation.

The SCL gene (also called Tal-1 or TCL5) was identified because of its association with chromosomal translocations in childhood T-cell lymphoid leukemias. SCL codes for a basic helix-loop-helix (bHLH) factor that can function as a transcriptional activator or repressor. In the adult, SCL expression is restricted to hematopoietic cells and tissues, but its function in the process of lineage commitment is unknown. The present study was designed to address the role of SCL in hematopoietic cell differentiation. SCL expression was determined in primary hematopoietic cells through the screening of cDNA samples obtained by reverse transcription-polymerase chain reaction (RT-PCR) from single cells at different stages of differentiation. SCL RNA expression was highest in bipotential and committed erythroid precursors and diminished with subsequent maturation to proerythroblasts and normoblasts. In contrast, SCL mRNA was low to undetectable in precursors of granulocytes and monocytes and their maturing progeny. The same pattern of expression was observed after erythroid or monocytic differentiation of a bipotent cell line, TF-1, in that SCL mRNA levels remained elevated during erythroid differentiation and were downregulated with monocytic differentiation. Accordingly, TF-1 was chosen as a model to investigate the functional significance of this divergent pattern of SCL expression in the two lineages. Four independent clones stably transfected with an SCL expression vector exhibited enhanced spontaneous and delta-aminolevulinic acid-induced erythroid differentiation as measured by glycophorin expression and hemoglobinization, consistent with the view that SCL is a positive regulator of erythroid differentiation. Furthermore, constitutive SCL expression interfered with monocytic differentiation, as assessed by the generation of adherent cells and the expression of Fc gamma RII in response to TPA. These results suggest that the downregulation of SCL may be required for monocytic differentiation.

Adult↗
PubMed1995

Divergent signal transduction pathways and effects on natural killer cell functions induced by interaction of Fc receptors with physiologic ligands or antireceptor antibodies.

Natural killer (NK) cells express receptors that bind to the Fc portion of immunoglobulin molecules (FcR), and their function can potentially be modulated positively or negatively by such receptor:ligand interactions. This review discusses recent developments in the understanding of expression of various forms and isoforms of FcRs by NK cells, and the sequelae of binding of physiologic ligands. Particular attention is paid to the significance of FcR:Ig interactions in both activating and inactivating NK cells under various conditions.

Animals↗
PubMed1987

Three Drosophila beta-tubulin sequences: a developmentally regulated isoform (beta 3), the testis-specific isoform (beta 2), and an assembly-defective mutation of the testis-specific isoform (B2t8) reveal both an ancient divergence in metazoan isotypes and structural constraints for beta-tubulin function.

The genomic DNA sequence and deduced amino acid sequence are presented for three Drosophila melanogaster beta-tubulins: a developmentally regulated isoform beta 3-tubulin, the wild-type testis-specific isoform beta 2-tubulin, and an ethyl methanesulfonate-induced assembly-defective mutation of the testis isoform, B2t8. The testis-specific beta 2-tubulin is highly homologous to the major vertebrate beta-tubulins, but beta 3-tubulin is considerably diverged. Comparison of the amino acid sequences of the two Drosophila isoforms to those of other beta-tubulins indicates that these two proteins are representative of an ancient sequence divergence event which at least preceded the split between lines leading to vertebrates and invertebrates. The intron/exon structures of the genes for beta 2- and beta 3-tubulin are not the same. The structure of the gene for the variant beta 3-tubulin isoform, but not that of the testis-specific beta 2-tubulin gene, is similar to that of vertebrate beta-tubulins. The mutation B2t8 in the gene for the testis-specific beta 2-tubulin defines a single amino acid residue required for normal assembly function of beta-tubulin. The sequence of the B2t8 gene is identical to that of the wild-type gene except for a single nucleotide change resulting in the substitution of lysine for glutamic acid at residue 288. This position falls at the junction between two major structural domains of the beta-tubulin molecule. Although this hinge region is relatively variable in sequence among different beta-tubulins, the residue corresponding to glu 288 of Drosophila beta 2-tubulin is highly conserved as an acidic amino acid not only in all other beta-tubulins but in alpha-tubulins as well.

Amino Acid Sequence↗
PubMedDate not supplied

Optical imaging of orientation and ocular dominance maps in area 17 of cats with convergent strabismus.

Strabismus (or squint) is both a well-established model for developmental plasticity of the brain and a frequent clinical symptom. While the layout and topographic relationship of functional domains in area 17 of divergently squinting cats has been analyzed extensively in recent years (e.g. Löwel et al., 1998), functional maps in convergently squinting animals have so far not been visualized with comparable detail. We have therefore investigated the functional organization of area 17 in adult cats with a surgically induced convergent squint angle. In these animals, visual acuity was determined by both behavioral tests and recordings of visual evoked potentials, and animals with comparable acuities in both eyes were selected for further experiments. The functional layout of area 17 was visualized using optical imaging of intrinsic signals. Monocular iso-orientation domains had a patchy appearance and their layout was different for left and right eye stimulation, so that segregated ocular dominance domains could be visualized. Iso-orientation domains exhibited a pinwheel-like organization, as previously described for normal and divergently squinting cats. Mean pinwheel density was the same in the experimental and control animals (3.4 pinwheel centers per mm2 cortical surface), but significantly (P < 0.00001) higher than that reported previously for normal and divergently squinting cats (2.7/mm2). A comparison of orientation with ocular dominance maps revealed that iso-orientation domains were continuous across the borders of ocular dominance domains and tended to intersect these borders at steep angles. However, in contrast to previous reports in normally raised cats, orientation pinwheel centers showed no consistent topographical relationship to the peaks of ocular dominance domains. Taken together, these observations indicate an overall similarity between the functional layout of orientation and ocular dominance maps in area 17 of convergently and divergently squinting cats. The higher pinwheel densities compared with previous reports suggest that animals from different gene pools might generally differ in this parameter and therefore also in the space constants of their cortical orientation maps.

Animals↗
PubMed1999

Sequence evolution in bacterial endosymbionts having extreme base compositions.

A major limitation on ability to reconstruct bacterial evolution is the lack of dated ancestors that might be used to evaluate and calibrate molecular clocks. Vertically transmitted symbionts that have cospeciated with animal hosts offer a firm basis for calibrating sequence evolution in bacteria, since fossils of the hosts can be used to date divergence events. Sequences for a functionally diverse set of genes have been obtained for bacterial endosymbionts (Buchnera) from two pairs of aphid host species, each pair diverging 50-70 MYA. Using these dates and estimated numbers of Buchnera generations per year, we calculated rates of base substitution for neutral and selected sites of protein-coding genes and overall rates for rRNA genes. Buchnera shows homogeneity among loci with regard to synonymous rate. The Buchnera synonymous rate is about twice that for low-codon-bias genes of Escherichia coli-Salmonella typhimurium on an absolute timescale, and fourfold higher on a generational timescale. Nonsynonymous substitutions show a greater rate disparity in favor of Buchnera, a result consistent with a genomewide decrease in selection efficiency in Buchnera. Ratios of synonymous to nonsynonymous substitutions differ for the two pairs of Buchnera, indicating that selection efficiency varies among lineages. Like numerous other intracellular bacteria, such as Rickettsia and Wolbachia, Buchnera has accumulated amino acids with codons rich in A or T. Phylogenetic reconstruction of amino acid replacements indicates that replacements yielding increased A + T predominated early in the evolution of Buchnera, with the trend slowing or stopping during the last 50 Myr. This suggests that base composition in Buchnera has approached a limit enforced by selective constraint acting on protein function.

AT Rich Sequence↗
PubMed1999

[Divergent asymmetries of the temporo-parietal cortical areas: anatomo-functional correlations and evolutionary and developmental implications].

Human brains present a clear asymmetry of the postero-lateral cortical area, so called "planum temporale" (Geschwind and Levitsky). This asymmetry is on favour of the left brain. A similar asymmetry is observed on the parietal operculum. MRI studies of 37 healthy volunteers have shown a clear difference between individuals. Mixing the index of temporal and parietal asymmetry, the authors consider four types: the most frequent pattern concerns 90% of right handed. For the others, 10% there are left handed as right handed. On conclusion, planum as many asymmetry and opercular asymmetry can be divergent, and both canan to determines handedness.

Adolescent↗
PubMedDate not supplied

Parametric scaling from species to growth-form diversity: an interesting analogy with multifractal functions.

We propose a measure of divergence from species to life-form diversity aimed at summarizing the ecological similarity among different plant communities without losing information on traditional taxonomic diversity. First, species and life-form relative abundances within a given plant community are determined. Next, using Rényi's generalized entropy, the diversity profiles of the analyzed community are computed both from species and life-form relative abundances. Finally, the speed of decrease from species to life-form diversity is obtained by combining the outcome of both profiles. Interestingly, the proposed measure shows some formal analogies with multifractal functions developed in statistical physics for the analysis of spatial patterns. As an application for demonstration, a small data set from a plant community sampled in the archaeological site of Paestum (southern Italy) is used.

Fractals↗
PubMed2005

Dissecting functional similarities of ribosome-associated chaperones from Saccharomyces cerevisiae and Escherichia coli.

Ribosome-tethered chaperones that interact with nascent polypeptide chains have been identified in both prokaryotic and eukaryotic systems. However, these ribosome-associated chaperones share no sequence similarity: bacterial trigger factors (TF) form an independent protein family while the yeast machinery is Hsp70-based. The absence of any component of the yeast machinery results in slow growth at low temperatures and sensitivity to aminoglycoside protein synthesis inhibitors. After establishing that yeast ribosomal protein Rpl25 is able to recruit TF to ribosomes when expressed in place of its Escherichia coli homologue L23, the ribosomal TF tether, we tested whether such divergent ribosome-associated chaperones are functionally interchangeable. E. coli TF was expressed in yeast cells that lacked the endogenous ribosome-bound machinery. TF associated with yeast ribosomes, cross-linked to yeast nascent polypeptides and partially complemented the aminoglycoside sensitivity, demonstrating that ribosome-associated chaperones from divergent organisms share common functions, despite their lack of sequence similarity.

Amino Acid Sequence↗
PubMed1991

[Children's respiratory health and air pollution].

Two surveys--one in children 9-11 living in an industrially polluted area, the other one on younger children in an urban environment--combined the collect of previous health impairments through a standardized questionnaire, clinical examination and respiratory functional testing with automatized air pollution measurement. Results confirmed those of similar surveys, that is the mildness of observed anomalies and the diverging perturbations: clinical symptoms without functional alterations or the reverse. Complementary research is therefore needed, if possible longitudinal.

Air Pollutants↗
PubMed2003

Retention of enzyme gene duplicates by subfunctionalization.

Duplication-degeneration-complementation (DDC) describes a process by which evolving duplicates of a pleiotropic ancestral gene divide up the multiple functions of the ancestor between them (i.e. subfunctionalize), and this ultimately frustrates the rate of pseudogene formation. Focusing explicitly on enzyme-like pleiotropic function, we model DDC driven by sequence divergence between duplicates. The model incorporates an idealized sequence-function mapping in which enzyme-substrate binding affinity is related to hydrophobic versus polar (HP) amino-acid composition of tertiary structure about the binding pocket. In this sense, a transparent coupling between physical-chemical function of an enzyme and sequence evolution is presented.

Enzymes↗
PubMed1990

The insulin receptor. A multifunctional protein.

The insulin receptor is a multifunctional protein encoded by a modular gene. Certain discrete domains within the insulin-receptor structure subserve specific functional properties. In some instances, these discrete domains are encoded by individual exons. This organizational model of the insulin receptor predicts the existence of divergent signaling pathways facilitating specific bioeffects. Some of these signaling pathways are shared with the closely related insulinlike growth factor I receptor (convergent pathways), whereas others are different (divergent). The concept of discrete functional domains also provides several mechanisms whereby inactive insulin receptors (no kinase activity) can inhibit the function of normal receptors. The ability of kinase-inactive insulin receptors to inhibit the signaling function of normal insulin receptors may be an operative mechanism in certain insulin-resistant states.

Adenosine Triphosphate↗
PubMed2006

Scaling laws at the phase transition of systems with divergent order parameter and/or internal length: the example of DNA denaturation.

We used the transfer-integral method to compute, with an uncertainty smaller than 5%, the six fundamental characteristic exponents of two dynamical models for DNA thermal denaturation and investigate the validity of the scaling laws. Doubts concerning this point arise because the investigated systems (i) have a divergent internal length, (ii) are described by a divergent order parameter, and (iii) are of dimension 1. We found that the assumption that the free energy can be described by a single homogeneous function is robust, despite the divergence of the order parameter, so that Rushbrooke's and Widom's identities are valid relations. Josephson's identity is instead not satisfied. This is probably due to the divergence of the internal length, which invalidates the assumption that the correlation length is solely responsible for singular contributions to thermodynamic quantities. Fisher's identity is even more wrong. We showed that this is due to the d=1 dimensionality and obtained an alternative law, which is well satisfied at DNA thermal denaturation.

Base Sequence↗
PubMed2006

Transposable element derived DNaseI-hypersensitive sites in the human genome.

BACKGROUND: Transposable elements (TEs) are abundant genomic sequences that have been found to contribute to genome evolution in unexpected ways. Here, we characterize the evolutionary and functional characteristics of TE-derived human genome regulatory sequences uncovered by the high throughput mapping of DNaseI-hypersensitive (HS) sites. RESULTS: Human genome TEs were found to contribute substantially to HS regulatory sequences characterized in CD4+ T cells: 23% of HS sites contain TE-derived sequences. While HS sites are far more evolutionarily conserved than non HS sites in the human genome, consistent with their functional importance, TE-derived HS sites are highly divergent. Nevertheless, TE-derived HS sites were shown to be functionally relevant in terms of driving gene expression in CD4+ T cells. Genes involved in immune response are statistically over-represented among genes with TE-derived HS sites. A number of genes with both TE-derived HS sites and immune tissue related expression patterns were found to encode proteins involved in immune response such as T cell specific receptor antigens and secreted cytokines as well as proteins with clinical relevance to HIV and cancer. Genes with TE-derived HS sites have higher average levels of sequence and expression divergence between human and mouse orthologs compared to genes with non TE-derived HS sites. CONCLUSION: The results reported here support the notion that TEs provide a specific genome-wide mechanism for generating functionally relevant gene regulatory divergence between evolutionary lineages. REVIEWERS: This article was reviewed by Wolfgang J. Miller (nominated by Jerzy Jurka), Itai Yanai and Mikhail S.Gelfand.

Journal Article↗
PubMed2006

Nonrandom divergence of gene expression following gene and genome duplications in the flowering plant Arabidopsis thaliana.

BACKGROUND: Genome analyses have revealed that gene duplication in plants is rampant. Furthermore, many of the duplicated genes seem to have been created through ancient genome-wide duplication events. Recently, we have shown that gene loss is strikingly different for large- and small-scale duplication events and highly biased towards the functional class to which a gene belongs. Here, we study the expression divergence of genes that were created during large- and small-scale gene duplication events by means of microarray data and investigate both the influence of the origin (mode of duplication) and the function of the duplicated genes on expression divergence. RESULTS: Duplicates that have been created by large-scale duplication events and that can still be found in duplicated segments have expression patterns that are more correlated than those that were created by small-scale duplications or those that no longer lie in duplicated segments. Moreover, the former tend to have highly redundant or overlapping expression patterns and are mostly expressed in the same tissues, while the latter show asymmetric divergence. In addition, a strong bias in divergence of gene expression was observed towards gene function and the biological process genes are involved in. CONCLUSION: By using microarray expression data for Arabidopsis thaliana, we show that the mode of duplication, the function of the genes involved, and the time since duplication play important roles in the divergence of gene expression and, therefore, in the functional divergence of genes after duplication.

Amino Acid Substitution↗
PubMed1993

A validation study of the domains of the core EORTC quality of life questionnaire.

A cohort study was conducted to investigate the construct validity of the domains of the EORTC QLQ-C30 (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire). Ninety-six patients undergoing chemotherapy at the Kingston Regional Cancer Centre, Kingston, Canada were given the EORTC QLQ-C30 and two out of four comparison scales; the Sickness Impact Profile, the McGill Pain Questionnaire, the General Health Questionnaire and the Cancer Rehabilitation Evaluation System, to complete during their clinic visits. Using the multitrait-multimethod matrix to examine relationships, the Spearman ranked correlation coefficients of similar and dissimilar domains between the EORTC QLQ-C30 and the comparison scales were compared. The EORTC QLQ-C30 domains of pain and physical and role functioning performed well in that they converged and diverged appropriately with the other instruments. The domain of psychological functioning had strong associations with domains thought to be dissimilar (social interaction and fatigue). Social interaction and financial impact diverged across dissimilar domains. This lack of specificity may relate to question wording. The symptom domain had strong associations with other domains across the comparison scales. This study shows that the domains of the EORTC QLQ-C30 have substantial construct validity in the multidimensional assessment of the quality of life of cancer patients and identifies where further work is required.

Adult↗
PubMed1981

Dichotic listening by brain-injured adults: observation of divergent test responses.

Research on central functions presents difficult problems, including heterogeneity among normals and subjects with central nervous system (CNS) defects. General conclusions are that there is an ear advantage related to cerebral dominance; testing for results of CNS damage requires stimuli of reduced redundancy; and fusion of dichotic stimuli is a brainstem function. Responses to digits presented dichotically were obtained. Data were in agreement with the usual findings that brain injury results in a reduced ability to understand dichotic speech and that injury to the dominant cerebral hemisphere results in lower speech perception via the opposite ear than by the ipsilateral ear. Significantly almost one third of the subjects performed differently than other members of their respective subgroups. A direction for additional research is to consider factors in otherwise apparently homogeneous groups that lead to nonhomogenous responses.

Adult↗