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Sleep in post-traumatic stress disorder and panic: convergence and divergence.

Disturbed sleep is a common clinical problem in anxiety disorders, particularly in patients with post-traumatic stress disorder (PTSD) and panic disorder (PD). Several studies have attempted to validate the subjective sleep complaints of these disorders using laboratory polysomnography. These attempts, typically focusing on PTSD or PD independently, have demonstrated inconsistent results. To our knowledge, no such studies have attempted to directly compare and contrast sleep disturbances in PTSD and PD together. Our review of the studies of subjective sleep disturbances, sleep architecture, and sleep-related biologic phenomena suggests that a comparative characterization of sleep disturbances in these two disorders is timely. Such an inference is based on our identification of several areas of convergence and divergence between PTSD and PD found in the published literature, as well as our own preliminary investigations. Specifically, PTSD and PD seem to converge on several sleep-related parameters, namely, sleep quality, presence of episodic parasomnias, and movement time. They also appear to diverge in other important sleep-related areas such as respiratory disturbances and the particular phenomenological nature of episodic parasomnias, namely nightmares or nocturnal panic attacks. Investigations focusing on such overlapping phenomena may provide groundwork for further elucidation of central fear systems underlying these two disorders. Additionally, such sleep studies have the potential to provide important insights into ongoing efforts to develop a cohesive conceptual framework into the patho-physiologies of these disorders.

Animals↗

Convergent validity of two measures of the quality of life.

In the paper, a test of convergent validity is undertaken for two methods of quality of life assessment, one based on a shortened version of the Health Measurement Questionnaire and the other based on professional clinical judgement. The Nottingham Health Profile is used as the comparator, and the data derive from a sample of colorectal cancer patients. Criteria for convergent validity are established and both methods yield outcomes broadly consistent with such criteria.

Activities of Daily Living↗

Convergent transcription interferes with expression of the copy number control gene, copA, from plasmid R1.

The copy number control gene, copA, of plasmid R1 codes for an 80-nucleotide untranslatable RNA. In Escherichia coli minicells, some copA hybrid plasmids and R1 miniplasmids also express a transcript of 200 nucleotides. Only the small RNA mediates the CopA phenotype. The switch between 80- and 200-nucleotide RNA synthesis is shown to be caused by convergent transcription; if transcription proceeds in both directions the inactive larger RNA is synthesised; the active small RNA is formed when copA transcription is not opposed by transcription from the other direction. The data presented indicate that convergent transcription interferes with copA expression by abolishing or reducing normal copA transcription termination.

Journal Article↗

Attaining exponential convergence for the flux error with second- and fourth-order accurate finite-difference equations. II. Application to systems comprising first-order chemical reactions.

This article demonstrates that exponential convergence of the flux error can be achieved for any kinetic-diffusion system comprising an arbitrary number of (pseudo) first-order chemical reactions if the underlying PDEs are discretized as outlined for the box 2 or box 4 method in the preceding part of this article. By investigating the eigenvalues and eigenvectors of the first-order kinetic coupling matrix in general form the present article demonstrates that the simulation of any multispecies first-order kinetic diffusion system can be as accurately done as the simulation of a single representative one-species system. The Fourier coefficients governing the error level of the flux are much smaller in the limiting case of kinetic control as those reported in the preceding article for the limiting case of diffusion control. The higher rate of exponential convergence predicted on the basis of the mathematical model has been fully verified by the numerical results.

Journal Article↗

Techniques of convergent beam electron diffraction.

The techniques required to record standard convergent beam electron diffraction patterns in an analytical electron microscope are discussed in detail, with emphasis on the design of electron optics in commercial instruments. Practical comments are included on specimen preparation, the influence of crystal defects, tilting to major zone axes, and alignment of the instrument. The influence of parameters under experimental control such as probe size, accelerating voltage, temperature, specimen thickness, and convergence angle is discussed in detail. Some comments are included on the alignment and limitations of large angle patterns formed by a defocused probe.

Crystallography↗

Convergent beam diffraction studies of interfaces, defects, and multilayers.

This paper explains how the convergent beam electron diffraction (CBED) and large angle convergent beam (LACBED) techniques can be used to study crystal defects, bicrystals, and multilayers. It is shown how the LACBED technique in particular can be used to derive the magnitude and sign of the Burgers vectors of dislocations and displacements at stacking faults. For bicrystals and multilayers examined in plan-view, LACBED gives the rocking curve for a chosen reflection. This enables layer strains to be measured to approximately 0.1% and composition profiles derived for both periodic and aperiodic structures. It is shown that a simple kinematic approach can be used to interpret the essential results in most cases.

Chemical Phenomena↗

Larval development of Phoronis pallida (Phoronida): implications for morphological convergence and divergence among larval body plans.

Morphological variation among larval body plans must be placed into a phylogenetic and ecological context to assess whether similar morphologies are the result of phylogenetic constraints or convergent selective pressures. Investigations are needed of the diverse larval forms within the Lophotrochozoa, especially the larvae of phoronids and brachiopods. The actinotroch larva of Phoronis pallida (Phoronida) was reared in the laboratory to metamorphic competence. Larval development and growth were followed with video microscopy, SEM, and confocal microscopy. Early developmental features were similar to other phoronid species. Gastrulation was accomplished by embolic invagination of the vegetal hemisphere. Mesenchymal cells were found in the remaining blastocoelic space after invagination began. Mesenchymal cells formed the body wall musculature during the differentiation of larval features. Body wall musculature served as the framework from which all other larval muscles proliferated. Larval growth correlated best with developmental stage rather than age. Consistent with other phoronid species, differentiation of juvenile tissues occurred most rapidly at the latest stages of larval development. The minimum precompetency period of P. pallida was estimated to be approximately 4-6 weeks. Previously published studies have documented that the planktonic embryos of P. pallida develop faster than the brooded embryos of P. vancouverensis. However, these data showed that the difference in developmental rate between the two species decreased in succeeding larval stages. There may be convergent selective pressures that result in similar timing to metamorphic competence among phoronid and brachiopod planktotrophic larval types. Morphological differences between these larval types result from heterochronic developmental shifts in the differentiation of juvenile tissue. Similarities in the larval morphology of phoronids and basal deuterostomes are likely the result of functional and developmental constraints rather than a shared (recent) evolutionary origin. These constraints are imposed by the functional design of embryological stages, feeding structures, and swimming structures.

Animals↗

Convergent evolution of sexual shape dimorphism in Diptera.

Several patterns of sexual shape dimorphism, such as male body elongation, eye stalks, or extensions of the exoskeleton, have evolved repeatedly in the true flies (Diptera). Although these dimorphisms may have evolved in response to sexual selection on male body shape, conserved genetic factors may have contributed to this convergent evolution, resulting in stronger phenotypic convergence than might be expected from functional requirements alone. I compared phenotypic variation in body shape in two distantly related species exhibiting sexually dimorphic body elongation: Prochyliza xanthostoma (Piophilidae) and Telostylinus angusticollis (Neriidae). Although sexual selection appears to act differently on male body shape in these species, they exhibited strikingly similar patterns of sexual dimorphism. Likewise, patterns of within-sex shape variation were similar in the two species, particularly in males: relative elongation of the male head capsule, antenna, and legs was associated with reduced head capsule width and wing length, but was nearly independent of variation in thorax length. However, the two species presented contrasting patterns of static allometry: male sexual traits exhibited elevated allometric slopes in T. angusticollis, but not in P. xanthostoma. These results suggest that a shared pattern of covariation among traits may have channeled the evolution of sexually dimorphic body elongation in these species. Nonetheless, static allometries may have been shaped by species-specific selection pressures or genetic architectures.

Animals↗

Mitogen- and stress-activated protein kinase 1: convergence of the ERK and p38 pathways in Alzheimer's disease.

Two of the earliest manifestations of the selective neurodegeneration that occurs in Alzheimer's disease (AD) involve the oxidative modification of various biomacromolecules and the reexpression of a multitude of cell cycle-related proteins. Taken together with the proximal and ectopic increases in activated components of the ERK and p38 pathways, involved in mitotic and cellular stress signaling, respectively, there is a clear and important role for mitotic and oxidative insults in the pathogenesis of AD. Despite the mounting evidence, however, for the causal role of mitogenic abnormalities and oxidative stress in AD pathogenesis, the effect of the converging relevant pathways due to chronic stimulation in AD remains largely unknown. To delineate further the mechanism by which mitogenic and stress signaling cascades converge, we focused on one of the downstream effectors of activated ERK and p38, mitogen- and stress-activated kinase 1 (MSK1). Activated MSK1, phosphorylated at residues Ser376 and Thr581, was upregulated in vulnerable neurons in AD when compared to that in age-matched controls, whereas MSK1 phosphorylated at residue Ser360 was not increased in AD. Furthermore, activated MSK1 phosphorylated at Thr581 colocalized strongly with activated p38 but only weakly with activated ERK, whereas MSK1 phosphorylated at Ser376 colocalized strongly with activated ERK but only weakly with activated p38, suggesting potential preferential phosphorylation sites for the two upstream effectors.

Aged↗

Genomic convergence to identify candidate genes for Parkinson disease: SAGE analysis of the substantia nigra.

Genomic convergence is a multistep approach that combines gene expression with genomic linkage to identify and prioritize susceptibility genes for complex disease. As a first step, we previously performed linkage analysis on 174 multiplex Parkinson's disease (PD) families, identifying five peaks for PD risk and two for genes affecting age at onset (AAO) in PD [Hauser et al., Hum Mol Genet 2003;12:671-677]. We report here the next step: serial analysis of gene expression [SAGE; Scott et al., JAMA 2001;286:2239-2242] to analyze substantia nigra tissue from three PD patients and two age-matched controls. We find 933 differentially expressed genes (P<0.05) between PD and controls, but of these, only 50 genes represented by unique SAGE tags map within our previously described PD linkage regions. Furthermore, genes encoded by mitochondrial DNA are expressed 1.5-fold higher in PD patients versus controls, without an increase in the corresponding nuclear-encoded mitochondrial components, suggesting an increase in mtDNA genomes in PD or a disjunction with nuclear expression. The next step in the genomic convergence process will be to screen these 50 high-quality candidate genes for association with PD risk susceptibility and genetic effects on AAO.

Aged↗

Assessing equilibration and convergence in biomolecular simulations.

If molecular dynamics simulations are used to characterize the folding of peptides or proteins, a wide range of conformational states needs to be sampled. This study reports an analysis of peptide simulations to identify the best methods for assessing equilibration and sampling in these systems where there is significant conformational disorder. Four trajectories of a beta peptide in methanol and four trajectories of an alpha peptide in water, each of 5 ns in length, have been studied. Comparisons have also been made with two 50-ns trajectories of the beta peptide in methanol. The convergence rates of quantities that probe both the extent of conformational sampling and the local dynamical properties have been characterized. These include the numbers of hydrogen bonds populated, clusters identified, and main chain torsion angle transitions in the trajectories. The relative equilibrium rates of different quantities are found to vary significantly between the two systems studied reflecting both the differences in peptide primary structure and the different solvents used. A cluster analysis of the simulation trajectories is identified as a very effective method for judging the convergence of the simulations. This is particularly the case if the analysis includes a comparison of multiple trajectories calculated for the same system from different starting structures.

Amino Acid Sequence↗

Genomic convergence and suppression of centrosome hyperamplification in primary p53-/- cells in prolonged culture.

Chromosome instability, a major property of cancer cells, is believed to promote mutations that establish malignant phenotypes. Centrosome hyperamplification and the consequential increase in the frequency of aberrant mitoses are the major causes of chromosome instability in cancer cells that lack the functional p53 tumor suppressor protein. Here, we examined dynamic changes of chromosome and centrosome behaviors during long-term culturing of primary epithelial cells derived from p53-null mice. The heterogeneity in the number of chromosomes per cell in the early to mid passage cell population diminished in late passage cells, giving rise to distinct subpopulations of cells. Concomitantly, centrosome hyperamplification that was observed at a high frequency in early to mid passage cells was suppressed in late passage cells. These results provide an explanation for the frequent observations that some cancer cell lines and tissues that lack functional p53 show normal centrosome behaviors and altered, yet relatively stable, chromosomes. Moreover, our in vitro findings may provide a model for possible genomic convergence in cultured cells. This may be analogous to the genomic convergence model proposed for in vivo tumor progression in which chromosome instability initially imposed during tumorigenesis becomes suppressed when neoplastic cells have acquired chromosome compositions that promise an optimal growth in a given environment.

Animals↗

EGF and beta1 integrin convergently regulate migration of A431 carcinoma cell through MAP kinase activation.

We found that the convergently epidermal growth factor (EGF)-induced signal and the collagen-induced signal activate mitogen-activated protein kinase (MAPK), which induces migration. We examined the signaling mechanisms of EGF-induced cell migration on collagen using the A431 carcinoma cell. EGF (10 ng/ml) induced migration on collagen, but inhibited proliferation. Using a MAPK cascade inhibitor, PD98059, it was shown that EGF-induced migration on collagen was mediated by MAPK whereas EGF-induced migration on fibronectin and vitronectin was not. PD98059 also showed that activation of MAPK induced by EGF enhanced the adhesiveness of A431 cells to collagen. By Western blotting analysis, the kinetics of MAPK phosphorylation induced by EGF and collagen was examined separately, and convergently. First of all, EGF without collagen caused transient MAPK phosphorylation. Collagen without EGF caused MAPK to be immediately and transiently dephosphorylated, and rephosphorylated followed by sustained hyperphosphorylation. EGF together with collagen caused an immediate, and sustained, hyperphosphorylation. These facts suggest that the transient MAPK dephosphorylation induced by collagen is required for migration in order to maintain an appropriate level of sustained phosphorylation. Furthermore, we found that adhesion of A431 cells to collagen was blocked by the anti-beta1 integrin antibody or by the mixed antibodies composed of anti-alpha1, -alpha2, and -alpha3 antibodies, indicating that collagen-induced MAPK phosphorylation was mediated through alpha1beta1, alpha2beta1, and alpha3beta1 integrins.

Cell Movement↗

Three-dimensional view of the surface motif associated with the P-loop structure: cis and trans cases of convergent evolution.

Here we identify the determinants of the nucleotide-binding ability associated with the P-loop-containing proteins, inferring their functional importance from their structural convergence to a unique three- dimensional (3D) motif. (1) A new surface 3D pattern is identified for the P-loop nucleotide-binding region, which is more selective than the corresponding sequence pattern; (2) the signature displays one residue that we propose is the determinant for the guanine-binding ability (the residues aligned to ras D119; this residue is known to be important only in the G-proteins, we extend the prediction to all the other P-loop- containing proteins); and (3) two cases of convergent evolution at the molecular level are highlighted in the analysis of the active site: the positive charge aligned to ras K117 and the arginine residues aligned to the GAP arginine finger. The analysis of the residues conserved on protein surfaces allows one to identify new functional or evolutionary relationships among protein structures that would not be detectable by conventional sequence or structure comparison methods.

Adenosine Triphosphate↗

Molecular mechanism of convergent regulation of brain Na(+) channels by protein kinase C and protein kinase A anchored to AKAP-15.

Activation of D1-like dopamine (DA) receptors reduces peak Na(+) current in hippocampal neurons voltage-dependent in a manner via phosphorylation of the alpha subunit. This modulation is dependent upon activation of cAMP-dependent protein kinase (PKA) and requires phosphorylation of serine 573 (S573) in the intracellular loop connecting homologous domains I and II (L(I-II)) by PKA anchored to A kinase anchoring protein-15 (AKAP-15). Activation of protein kinase C (PKC) also reduces peak Na(+) currents and enhances the strength of the PKA modulatory pathway. Here we probe the molecular mechanism responsible for the convergent effects of PKA and PKC on brain Na(v)1.2a channels. Analysis of the interaction of AKAP-15 with the intracellular loops of the Na(v)1.2a channel shows that it binds to L(I-II), thereby targeting PKA directly to its sites of phosphorylation on the Na(+) channel by specific protein-protein interactions. Mutagenesis and expression experiments indicate that reduction of peak Na(+) current by PKC requires S554 and S573 in L(I-II) in addition to S1506 in the inactivation gate. In addition, PKC-dependent phosphorylation of S576 in L(I-II) is necessary for enhancement of PKA modulation of brain Na(+) channels. When S576 is phosphorylated by PKC, the increase in modulation by PKA activation requires phosphorylation of S687 in L(I-II). Thus, the maximal modulation of these Na(+) channels by concurrent activation of PKA and PKC requires phosphorylation at four distinct sites in L(I-II): S554, S573, S576, and S687. This convergent regulation provides a novel mechanism by which information from multiple signaling pathways may be integrated at the cellular level in the hippocampus and throughout the central nervous system.

A Kinase Anchor Proteins↗

Convergence properties of a modified Hopfield-Tank model.

The neural network model of Hopfield and Tank applied to the Travelling Salesman Problem, has been analyzed in order to improve its convergence properties. A simple change of the parameter sets always allows to reach states corresponding to valid tours. Besides a more interesting modification has been presented by adding a new term to force expression. This modified model has a high value of convergence and it is able to find short tours. So, more confidence can be given to these type of models, and real applications could be performed.

Algorithms↗

Self-organizing maps: ordering, convergence properties and energy functions.

We investigate the convergence properties of the self-organizing feature map algorithm for a simple, but very instructive case: the formation of a topographic representation of the unit interval [0, 1] by a linear chain of neurons. We extend the proofs of convergence of Kohonen and of Cottrell and Fort to hold in any case where the neighborhood function, which is used to scale the change in the weight values at each neuron, is a monotonically decreasing function of distance from the winner neuron. We prove that the learning dynamics cannot be described by a gradient descent on a single energy function, but may be described using a set of potential functions, one for each neuron, which are independently minimized following a stochastic gradient descent. We derive the correct potential functions for the one- and multi-dimensional case, and show that the energy functions given by Tolat (1990) are an approximation which is no longer valid in the case of highly disordered maps or steep neighborhood functions.

Algorithms↗

Convergence of skin reflex and corticospinal effects in segmental and propriospinal pathways to forelimb motoneurones in the cat.

The organization of facilitatory convergence from cutaneous afferents (Skin) and the corticospinal tract (pyramidal tract, Pyr) in pathways to forelimb motoneurones of mainly distal muscles was studied in anaesthetized cats by analysing postsynaptic potentials (PSPs), which were spatially facilitated by combinations of stimuli to the two sources at different time intervals. Conditioning Pyr volleys facilitated Skin-evoked PSPs of fixed (1.2-3.6 ms) central latencies (Skin PSPs), suggesting that disynaptic and polysynaptic skin reflex pathways are facilitated from the pyramidal tract. The shortest latencies (1.2-1.7 ms) of pyramidal facilitation suggested direct connection of pyramidal fibres with last order neurones of skin reflex pathways. Conditioning Skin volleys facilitated Pyr-evoked PSPs of fixed, mostly disynaptic latencies (1.0-2.5 ms; Pyr PSPs), suggesting that pyramido-motoneuronal pathways are facilitated from Skin at a premotoneuronal level. The shortest pathway from skin afferents to the premotor neurones appeared to be monosynaptic. Although Pyr and Skin volleys were mutually facilitating, the facilitation curve of Pyr PSPs and that of Skin PSPs were discontinuous to each other, with the peak facilitation at different Skin-Pyr volley intervals. Transection of the dorsal column (DC) at the C5/C6 border had little effect on the latencies or amplitudes evoked by maximal stimulation and the pyramidal facilitation of Skin PSPs. In contrast, the facilitation of Pyr PSPs by Skin stimulation was greatly decreased after the DC transection, and the facilitation curve of Pyr PSPs was continuous to that of Skin PSPs, with no separate peak. Latencies of Pyr PSPs ranged similarly to those in DC intact preparations. More rostral DC transection (C4/C5 border) reduced Skin-facilitated Pyr excitatory PSPs (EPSPs) less than C5/C6 lesions, suggesting that the C5 segment also contains neurones mediating Skin-facilitated Pyr EPSPs. The results show that convergence from skin afferents and the corticospinal tract occurs at premotor pathways of different cervical segments. We suggest that corticospinal facilitation of skin reflex occurs mostly in the brachial segments and Skin facilitation of cortico-motoneuronal effects takes place largely in the rostral cervical segments and partly in the brachial segments.

Animals↗