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Signal transmission through the dark-adapted retina of the toad (Bufo marinus). Gain, convergence, and signal/noise.

Responses to light were recorded from rods, horizontal cells, and ganglion cells in dark-adapted toad eyecups. Sensitivity was defined as response amplitude per isomerization per rod for dim flashes covering the excitatory receptive field centers. Both sensitivity and spatial summation were found to increase by one order of magnitude between rods and horizontal cells, and by two orders of magnitude between rods and ganglion cells. Recordings from two hyperpolarizing bipolar cells showed a 20 times response increase between rods and bipolars. At absolute threshold for ganglion cells (Copenhagen, D.R., K. Donner, and T. Reuter. 1987. J. Physiol. 393:667-680) the dim flashes produce 10-50-microV responses in the rods. The cumulative gain exhibited at each subsequent synaptic transfer from the rods to the ganglion cells serves to boost these small amplitude signals to the level required for initiation of action potentials in the ganglion cells. The convergence of rod signals through increasing spatial summation serves to decrease the variation of responses to dim flashes, thereby increasing the signal-to-noise ratio. Thus, at absolute threshold for ganglion cells, the convergence typically increases the maximal signal-to-noise ratio from 0.6 in rods to 4.6 in ganglion cells.

Action Potentials↗

Parental Care: The Key to Understanding Endothermy and Other Convergent Features in Birds and Mammals.

Birds and mammals share a number of features that are remarkably similar but that have evolved independently. One of these characters, endothermy, has been suggested to have played a cardinal role in avian and mammalian evolution. I hypothesize that it is parental care, rather than endothermy, that is the key to understanding the amazing convergence between mammals and birds. Endothermy may have arisen as a consequence of selection for parental care because endothermy enables a parent to control incubation temperature. The remarkable ability of many birds and mammals to sustain vigorous exercise may also have arisen as a consequence of selection for parental care because provisioning of offspring often requires sustained vigorous exercise. Because extensive parental care encompasses a wide range of behaviors, morphology, and physiology, it may be a key innovation that accounts for the majority of convergent avian and mammalian characters.

Journal Article↗

Convergent evolution and divergent selection: lizards at the White Sands ecotone.

Ecological transition zones, where organismal phenotypes result from a delicate balance between selection and migration, highlight the interplay of local adaptation and gene flow. Here, I study the response of an entire species assemblage to natural selection across a common ecotone. Three lizard species, distributed along a dramatic environmental gradient in substrate color, display convergent adaptation of blanched coloration on the gypsum dunes of White Sands National Monument. I investigate the role of gene flow in modulating phenotypic response to selection by quantifying color variation and genetic variation across the ecotone. I find species differences in degree of background matching and in genetic connectivity of populations across the ecotone. Differences among species in phenotypic response to selection scale precisely to levels of genetic isolation. Species with higher levels of gene flow across the ecotone exhibit less dramatic responses to selection. Results also reveal a strong signal of ecologically mediated divergence for White Sands lizards. For all species, phenotypic variation is better explained by habitat similarity than genetic similarity. Convergent evolution of blanched coloration at White Sands clearly reflects the action of strong divergent selection; however, adaptive response appears to be modulated by gene flow and demographic history and can be predicted by divergence-with-gene-flow models.

Animals↗

The problem of isotropically orienting N converging vectors in space with application to radiotherapy planning.

This note presents the solutions to the problem of orienting N converging vectors with a common origin in space with maximal separation for N = 3,4,...,8. With a specific definition of maximal separation, an algorithm was developed and coded which iteratively converges to the solutions. It has been suggested that these orientations might be appropriate for photon beam directions in conformal radiotherapy. When N = 4, the solution is the previously proposed tetrad geometry. The solutions for other N are discussed.

Algorithms↗

Computerized optimization of multiple isocentres in stereotactic convergent beam irradiation.

A method for the fully computerized determination and optimization of positions of target points and collimator sizes in convergent beam irradiation is presented. In conventional interactive trial and error methods, which are very time consuming, the treatment parameters are chosen according to the operator's experience and improved successively. This time is reduced significantly by the use of a computerized procedure. After the definition of target volume and organs at risk in the CT or MR scans, an initial configuration is created automatically. In the next step the target point positions and collimator diameters are optimized by the program. The aim of the optimization is to find a configuration for which a prescribed dose at the target surface is approximated as close as possible. At the same time dose peaks inside the target volume are minimized and organs at risk and tissue surrounding the target are spared. To enhance the speed of the optimization a fast method for approximate dose calculation in convergent beam irradiation is used. A possible application of the method for calculating the leaf positions when irradiating with a micromultileaf collimator is briefly discussed. The success of the procedure has been demonstrated for several clinical cases with up to six target points.

Arteriovenous Malformations↗

Improved estimation of the detector response function for converging beam collimators.

Converging beam collimator geometries offer improved tradeoffs between resolution and noise for single photon emission computed tomography (SPECT). The major factor limiting the resolution in SPECT is the collimator-detector response blurring. In order to compensate for this blurring it is useful to be able to calculate the collimator response function. A previous formulation presented a method for calculating the response for parallel and converging beam collimators that assumed that the shape of the holes did not change over the face of the collimator. However, cast collimators are fabricated using pins with a constant cross-section (shape perpendicular to the pin axis). As a result, due to the angulation of the pins, the holes made by these pins have shapes on the front and back faces of the collimator that change with position. This change in hole shape is especially pronounced when the angle between the collimator hole and the collimator normal is large, as is the case for half-fan-beam or short-focal-length collimators. This paper presents a derivation of a modification to the original method that accounts for the change in shape of the collimator holes. The method has been verified by comparing predicted line spread functions to experimentally measured ones for a collimator with a maximum hole angle of 35 degrees with respect to the normal. This formulation is useful for predicting the response of fan-beam collimators in the design process and for use in detector response compensation algorithms.

Equipment Design↗

Global convergence analysis of fast multiobjective gradient-based dose optimization algorithms for high-dose-rate brachytherapy.

We consider the problem of the global convergence of gradient-based optimization algorithms for interstitial high-dose-rate (HDR) brachytherapy dose optimization using variance-based objectives. Possible local minima could lead to only sub-optimal solutions. We perform a configuration space analysis using a representative set of the entire non-dominated solution space. A set of three prostate implants is used in this study. We compare the results obtained by conjugate gradient algorithms, two variable metric algorithms and fast-simulated annealing. For the variable metric algorithm BFGS from numerical recipes, large fluctuations are observed. The limited memory L-BFGS algorithm and the conjugate gradient algorithm FRPR are globally convergent. Local minima or degenerate states are not observed. We study the possibility of obtaining a representative set of non-dominated solutions using optimal solution rearrangement and a warm start mechanism. For the surface and volume dose variance and their derivatives, a method is proposed which significantly reduces the number of required operations. The optimization time, ignoring a preprocessing step, is independent of the number of sampling points in the planning target volume. Multiobjective dose optimization in HDR brachytherapy using L-BFGS and a new modified computation method for the objectives and derivatives has been accelerated, depending on the number of sampling points, by a factor in the range 10-100.

Algorithms↗

Convergence study of an accelerated ML-EM algorithm using bigger step size.

In SPECT/PET, the maximum-likelihood expectation-maximization (ML-EM) algorithm is getting more attention as the speed of computers increases. This is because it can incorporate various physical aspects into the reconstruction process leading to a more accurate reconstruction than other analytical methods such as filtered-backprojection algorithms. However, the convergence rate of the ML-EM algorithm is very slow. Several methods have been developed to speed it up, such as the ordered-subset expectation-maximization (OS-EM) algorithm. Even though OS-type algorithms can bring about significant acceleration in the iterative reconstruction, it is generally believed that ML-EM produces better images, in terms of statistical noise in the reconstruction. In this paper, we present an accelerated ML-EM algorithm with bigger step size and show its convergence characteristics in terms of variance noise and log-likelihood values. We also show some advantages of our method over other accelerating methods using additive forms.

Algorithms↗

Convergence of non-clathrin- and clathrin-derived endosomes involves Arf6 inactivation and changes in phosphoinositides.

The trafficking of two plasma membrane (PM) proteins that lack clathrin internalization sequences, major histocompatibility complex class I (MHCI), and interleukin 2 receptor alpha subunit (Tac) was compared with that of PM proteins internalized via clathrin. MHCI and Tac were internalized into endosomes that were distinct from those containing clathrin cargo. At later times, a fraction of these internalized membranes were observed in Arf6-associated, tubular recycling endosomes whereas another fraction acquired early endosomal autoantigen 1 (EEA1) before fusion with the "classical" early endosomes containing the clathrin-dependent cargo, LDL. After convergence, cargo molecules from both pathways eventually arrived, in a Rab7-dependent manner, at late endosomes and were degraded. Expression of a constitutively active mutant of Arf6, Q67L, caused MHCI and Tac to accumulate in enlarged PIP(2)-enriched vacuoles, devoid of EEA1 and inhibited their fusion with clathrin cargo-containing endosomes and hence blocked degradation. By contrast, trafficking and degradation of clathrin-cargo was not affected. A similar block in transport of MHCI and Tac was reversibly induced by a PI3-kinase inhibitor, implying that inactivation of Arf6 and acquisition of PI3P are required for convergence of endosomes arising from these two pathways.

ADP-Ribosylation Factor 6↗

Convergence of plant-rich and plant-only diets.

Discussants at the Third International Congress on Vegetarian Nutrition considered the nutritional adequacy, benefits, and health outcomes of plant-only (e.g., vegan and fruitarian), plant-based (e.g., macrobiotic, lactovegetarian, semivegetarian, and meatless), and omnivorous dietary patterns. The increased availability of a variety of plant foods, the advent of nutrient-fortified plant foods, the use of vitamin and mineral supplements, and the widespread dissemination of sound information on dietary patterns mean that convergence between the essential nutrient profiles of plant-only and plant-rich, plant-based diets is possible. Special attention should be paid to nutrition among vulnerable groups by age or physiologic status if they consume diets based solely on plants. Research has shown that both plant-only and plant-based eating patterns have health benefits, most notably in reducing the risk of chronic, degenerative diseases. The panel concluded that evidence for a convergence of scientific opinion on the safety and healthfulness of plant-only diets that are appropriately planned to meet all nutrient requirements compared with plant-based diets is considerable.

Diet, Macrobiotic↗

On the convergence of a clustering algorithm for protein-coding regions in microbial genomes.

MOTIVATION: As the number of fully sequenced prokaryotic genomes continues to grow rapidly, computational methods for reliably detecting protein-coding regions become even more important. Audic and Claverie (1998) Proc. Natl Acad. Sci. USA, 95, 10026-10031, have proposed a clustering algorithm for protein-coding regions in microbial genomes. The algorithm is based on three Markov models of order k associated with subsequences extracted from a given genome. The parameters of the three Markov models are recursively updated by the algorithm which, in simulations, always appear to converge to a unique stable partition of the genome. The partition corresponds to three kinds of regions: (1) coding on the direct strand, (2) coding on the complementary strand, (3) non-coding. RESULTS: Here we provide an explanation for the convergence of the algorithm by observing that it is essentially a form of the expectation maximization (EM) algorithm applied to the corresponding mixture model. We also provide a partial justification for the uniqueness of the partition based on identifiability. Other possible variations and improvements are briefly discussed.

Algorithms↗

Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells.

Estrogen receptors display high levels of promiscuity in accommodating a wide range of ligand structures, but the functional consequence of changing receptor conformations in complex with distinct agonists is highly controversial. To determine variations in the transactivation capacity induced by different estrogenic agonists, we assessed global transcriptional profiles elicited by natural or synthetic xenoestrogens in comparison with the endogenous hormone 17beta-estradiol. Human MCF7 and T47D carcinoma cells, representing the most frequently used model systems for tumorigenic responses in the mammary gland, were synchronized by hormone starvation during 48 h. Subsequently, a 24 h exposure was carried out with equipotent concentrations of the selected xenoestrogens or 17beta-estradiol. Analysis of messenger RNA was performed on high-density oligonucleotide microarrays that display the sequences of 33,000 human transcripts, yielding a total of 181 gene products that are regulated upon estrogenic stimulation. Surprisingly, genistein (a phytoestrogen), bisphenol-A and polychlorinated biphenyl congener 54 (two synthetic xenoestrogens) produced highly congruent genomic fingerprints by regulating the same range of human genes. Also, the monotonous genomic signature observed in response to xenoestrogens is identical to the transcriptional effects induced by physiological concentrations of 17beta-estradiol. This striking functional convergence indicates that the transcription machinery is largely insensitive to the particular structure of estrogen receptor agonists. The occurrence of such converging transcriptional programs reinforces the hypothesis that multiple xenoestrogenic contaminants, of natural or anthropogenic origin, may act in conjunction with the endogenous hormone to induce additive effects in target tissues.

Antineoplastic Agents↗

Interhemispheric integration: I. Symmetry and convergence of the corticocortical connections of the left and the right principal sulcus (PS) and the left and the right supplementary motor area (SMA) in the rhesus monkey.

The relationship between the termination zones of projections from paired homotopic areas in the frontal lobe was examined in the cerebral cortex of the macaque monkey. Injections of WGA-HRP and tritiated amino acids were made in topographically matched regions of the principal sulcus (PS) or the supplementary motor area (SMA) in each hemisphere, such that the projections from the same area on each side were differentially labeled in the same animal. Adjacent sections through the cortical regions that received bilateral inputs from these areas were processed for the respective tracers, permitting the relationship between the converging projections to be defined. Comparison of the cortical connections of the left and right PS or of the left and right SMA yielded two major findings. First, only minor differences in the topographic distribution and strength of connections of homotopic areas were observed, providing little evidence of asymmetry in the connections of either the PS or the SMA in the macaque. Second, with the exception of interdigitation observed in a portion of the dorsal bank of the PS, the cortical projections from both the left and the right PS and SMA converged (overlapped) in common columnar territories. These termination patterns allow for a remarkable degree of interhemispheric integration.

Animals↗

Convergence and plasticity of monoaminergic systems in the medial prefrontal cortex during the postnatal period: implications for the development of psychopathology.

A variety of observations have suggested that the dopamine and serotonin systems may play a role in the pathophysiology and treatment of major mental disorders of childhood, adolescence and early adulthood. A recent triple immunofluorescence study has demonstrated a convergence of serotonin and dopamine fibers onto both pyramidal cells and GABAergic interneurons in the rat medial prefrontal cortex (mPFCx). These findings are consistent with the results of an electrophysiological study conducted in another laboratory that suggested such a relationship exists in the pyriform cortex of the rodent brain. During postnatal development, the dopamine system shows a progressive ingrowth of fibers into this region that continues until the early adult period. In contrast, GABAergic neurons appear to complete their postnatal maturation by the fourth postnatal week (the early post-weanling period). As dopamine fibers infiltrate the rat mPFCx, they progressively increase their interaction with neural elements within the neuropil and with the cell bodies of both pyramidal cells and GABAergic interneurons. This process appears to be influenced by the serotonin system, since lesioning of the nucleus raphe dorsalis during the neonatal period results in a significant increase of dopamine fibers. This finding suggests that lesions of the serotonin system induce plasticity of the cortical dopamine system; however, it is not known whether this inferred suppressive effect of serotonin fibers occurs at brainstem levels or within the mPFCx itself. Taken together, these various studies suggest that the convergence of dopamine and serotonin fiber systems on intrinsic cortical neurons shows considerable plasticity during postnatal life that could theoretically contribute to the development of 'miswired' circuits in individuals with neuropsychiatric disorders.

Animals↗

Convergent and complementary projections of the caudal paralaminar thalamic nuclei to rat temporal and insular cortex.

Thalamic nuclei adjacent to the medial geniculate body play a pivotal role in processing of sensory stimuli during emotional situations. These nuclei, which include the suprageniculate nucleus (SG), the posterior intralaminar nucleus (PIN), the peripeduncular nucleus (PP) and the medial division of the medial geniculate body (MGm), project to both cortex and amygdala, but target areas and the extent of the projection of individual nuclei are not known yet. The aim of the present study was to analyze the contribution of individual nuclei to the cortical projection with modern sensitive tracing techniques. Small injections of Miniruby or PHA-L were made into single thalamic nuclei. All thalamic nuclei have in common a projection into the upper portion of layer I of the temporal aspect of the cortical mantle. Furthermore, SG, PIN, MGm and PP each demonstrated a convergent projection to lower layer III and to layer IV of the ectorhinal and visceral cortex. Only MGm projects to layer VI of primary auditory and temporal association cortices. Within the perirhinal cortex zones of convergence and divergence exist. The present results demonstrate a differential thalamocortical projection of single thalamic nuclei to those cortical areas which are involved in the transmission of sensory signals to the amygdala via the thalamocortico-cortical pathway and to the hippocampus via the entorhinal cortex. The thalamic nuclei are thus in a position to activate the amygdala and to modulate the information flow of the thalamocortico-cortical pathway to both amygdala and hippocampus.

Animals↗

Sub-area-specific Suppressive Interaction in the BOLD responses to simultaneous finger stimulation in human primary somatosensory cortex: evidence for increasing rostral-to-caudal convergence.

In the primary somatosensory cortex (SI) of non-human primates, receptive field properties have been shown to differ between its sub-areas with increasing convergence in areas 1 and 2 as compared with area 3b. In this study, we searched for a similar functional organization of human SI. We performed fMRI in healthy subjects during separate or simultaneous electrical stimulation of the second and third finger of the right hand. Activation patterns in response to stimulation of single fingers reflected the somatotopical arrangement within the hand area of SI. Somatotopy was more clear-cut in area 3b as compared with areas 1 and 2. The response to simultaneous stimulation was considerably smaller than the summed responses to separate stimulation of each finger alone, pointing to a suppressive interaction effect. A region-of-interest analysis in the representational areas of the second and third finger revealed sub-area-specific differential suppressive interaction with an increase along the rostral-caudal axis (areas 3b, 1 and 2: 26, 32.7 and 42.2%, respectively). These findings on differences in the topographic as well as functional organization between sub-areas of SI support the notion of increasing convergence and integration from area 3b to areas 1 and 2 in human subjects.

Adult↗

Exceptional convergent evolution in a virus.

Replicate lineages of the bacteriophage phiX 174 adapted to growth at high temperature on either of two hosts exhibited high rates of identical, independent substitutions. Typically, a dozen or more substitutions accumulated in the 5.4-kilobase genome during propagation. Across the entire data set of nine lineages, 119 independent substitutions occurred at 68 nucleotide sites. Over half of these substitutions, accounting for one third of the sites, were identical with substitutions in other lineages. Some convergent substitutions were specific to the host used for phage propagation, but others occurred across both hosts. Continued adaptation of an evolved phage at high temperature, but on the other host, led to additional changes that included reversions of previous substitutions. Phylogenetic reconstruction using the complete genome sequence not only failed to recover the correct evolutionary history because of these convergent changes, but the true history was rejected as being a significantly inferior fit to the data. Replicate lineages subjected to similar environmental challenges showed similar rates of substitution and similar rates of fitness improvement across corresponding times of adaptation. Substitution rates and fitness improvements were higher during the initial period of adaptation than during a later period, except when the host was changed.

Bacteriophage phi X 174↗

Polymorphism, shared functions and convergent evolution of genes with sequences coding for polyalanine domains.

Mutations causing expansions of polyalanine domains are responsible for nine hereditary diseases. Other GC-rich sequences coding for some polyalanine domains were found to be polymorphic in human. These observations prompted us to identify all sequences in the human genome coding for polyalanine stretches longer than four alanines and establish their degree of polymorphism. We identified 494 annotated human proteins containing 604 polyalanine domains. Thirty-two percent (31/98) of tested sequences coding for more than seven alanines were polymorphic. The length of the polyalanine-coding sequence and its GCG or GCC repeat content are the major predictors of polymorphism. GCG codons are over-represented in human polyalanine coding sequences. Our data suggest that GCG and GCC codons play a key role in polyalanine-coding sequence appearance and polymorphism. The grouping by shared function of polyalanine-containing proteins in Homo sapiens, Drosophila melanogaster and Caenorhabditis elegans shows that the majority are involved in transcriptional regulation. Phylogenetic analyses of HOX, GATA and EVX protein families demonstrate that polyalanine domains arose independently in different members of these families, suggesting that convergent molecular evolution may have played a role. Finally polyalanine domains in vertebrates are conserved between mammals and are rarer and shorter in Gallus gallus and Danio rerio. Together our results show that the polymorphic nature of sequences coding for polyalanine domains makes them prime candidates for mutations in hereditary diseases and suggests that they have appeared in many different protein families through convergent evolution.

Amino Acid Sequence↗