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At least 1,045 records · Page 58Linked to original sources
PubMed2004

Position of the CrPV IRES on the 40S subunit and factor dependence of IRES/80S ribosome assembly.

The cricket paralysis virus intergenic region internal ribosomal entry site (CrPV IGR IRES) can assemble translation initiation complexes by binding to 40S subunits without Met-tRNA(Met)(i) and initiation factors (eIFs) and then by joining directly with 60S subunits, yielding elongation-competent 80S ribosomes. Here, we report that eIF1, eIF1A and eIF3 do not significantly influence IRES/40S subunit binding but strongly inhibit subunit joining and the first elongation cycle. The IRES can avoid their inhibitory effect by its ability to bind directly to 80S ribosomes. The IRES's ability to bind to 40S subunits simultaneously with eIF1 allowed us to use directed hydroxyl radical cleavage to map its position relative to the known position of eIF1. A connecting loop in the IRES's pseudoknot (PK) III domain, part of PK II and the entire domain containing PK I are solvent-exposed and occupy the E site and regions of the P site that are usually occupied by Met-tRNA(Met)(i).

Animals↗
PubMedDate not supplied

[Arterial tortuosity syndrome].

The arterial tortuosity syndrome is a rare congenital disorder characterized by elongation and generalized tortuosity of the major arteries including the aorta. Associated clinical features consist of excessively stretchable skin and joint laxity which is indicative of a connective tissue disorder such as Ehlers-Danlos or Cutis laxa syndrome. The gene locus of the arterial tortuosity syndrome has recently been localised on chromosome 20q13; inheritance ist autosomal recessive. - We report on a newborn with arterial tortuosity syndrome and hiatal hernia, bilateral hip dislocation, inguinal hernias and diffuse tortuosity of the great arteries including the aorta. Known gene loci involved in Ehlers-Danlos syndrome, cutis laxa syndrome and other connective tissue disorders were excluded by specific DNA markers. By homozygosity mapping with polymorphic microsatellite markers it was possible to confirm the gene locus for the ATS on chromosome 20q13. In addition to the presentation of this patient, a review of the literature is presented.

Abnormalities, Multiple↗
PubMed1997

Neurotization of motor nerves innervating the lower extremity by utilizing the lower intercostal nerves.

An animal model in the rat was developed to study the reinnervation of ventral roots contributing to lower-extremity nerves by use of intercostal nerves. Intercostal nerves and distal cauda equina roots were anastomosed, using a collagen tube and microsurgical technique. Most experimental animals could lift their previously paralyzed legs and could walk with a severe limp by 9 months postoperatively. Recordings of nerve action potentials (NAPs) and muscle action potentials (MAPs) indicated that the intercostal and sciatic nerves had some functional connections. Histologic analysis 12 months after repair demonstrated axonal regeneration extending from the intercostal nerves to and down lumbar ventral roots. Most of the regenerated fibers were moderately well-myelinated. Connections between the neurons of the anterior horn cells in the lower thoracic spinal cord and the reinnervated sciatic nerve were confirmed by retrograde tracer, using fast blue.

Action Potentials↗
PubMed2004

Improved theoretical description of protein folding kinetics from rotations in the phase space of relevant order parameters.

A method is introduced to construct a better approximation for the reaction coordinate for protein folding from known order parameters. The folding of a two-state off-lattice alpha helical Go-type protein is studied using molecular dynamics simulations. Folding times are computed directly from simulation, as well as theoretically using an equation derived by considering Brownian-type dynamics for the putative reaction coordinate. Theoretical estimates of the folding time using the number of native contacts (Qn) as a reaction coordinate were seen to differ quite significantly from the true folding time of the protein. By considering the properties of the bimodal free energy surface of this protein as a function of Qn and another relevant coordinate for folding Q (the total number of contacts), we show that by introducing a rotation in the phase space of the order parameters Q and Qn, we can construct a new reaction coordinate q that leads to a fivefold improvement in the estimate of the folding rate. This new coordinate q, resulting from the rotation, lies along the line connecting the unfolded and folded ensemble minima of the free energy map plotted as a function of the original order parameters Q and Qn. Possible reasons for the remaining discrepancy between the folding time computed theoretically and from folding simulations are discussed.

Computer Simulation↗
PubMed1989

An investigation of trained neural networks from a neurophysiological perspective.

The application of theoretical neural networks to preprocessed images was investigated with the aim of developing a computational recognition system. The neural networks were trained by means of a back-propagation algorithm, to respond selectively to computer-generated bars and edges. The receptive fields of the trained networks were then mapped, in terms of both their synaptic weights and their responses to spot stimuli. There was a direct relationship between the pattern of weights on the inputs to the hidden units (the units in the intermediate layer between the input and the output units), and their receptive field as mapped by spot stimuli. This relationship was not sustained at the level of the output units in that their spot-mapped responses failed to correspond either with the weights of the connections from the hidden units to the output units, or with a qualitative analysis of the networks. Part of this discrepancy may be ascribed to the output function used in the back-propagation algorithm.

Algorithms↗
PubMed1994

Connectional topography in the zebrafish olfactory system: random positions but regular spacing of sensory neurons projecting to an individual glomerulus.

It is unknown how neuronal connections are specified in the olfactory system. To define rules of connectivity in this system, we investigated whether the projection of sensory neurons from the olfactory epithelium to the olfactory bulb is topographically ordered. By backtracking with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), we find that neurons projecting into a single identified glomerulus are widely dispersed over the olfactory epithelium. Their positions in the sensory surface do not predict their glomerulus specificity and are probably random. A statistical analysis reveals that neurons connected to the same glomerulus are spaced at distances of several cell diameters from each other. The convergence of projections to one point in the target area from neurons that are widely and evenly distributed in the sensory surface constitutes an unusual type of connectional topography that contrasts with the precise topological (neighborhood-preserving) maps found in other sensory systems. It may maximize the probability to detect odorants that activate a single glomerular unit.

Animals↗
PubMed2006

Mean number of visits to sites in Levy flights.

Formulas are derived to compute the mean number of times a site has been visited during symmetric Levy flights. Unrestricted Levy flights are considered first, for lattices of any dimension: conditions for the existence of finite asymptotic maps of the visits over the lattice are analyzed and a connection is made with the transience of the flight. In particular it is shown that flights on lattices of dimension greater than 1 are always transient. For an interval with absorbing boundaries the mean number of visits reaches stationary values, which are computed by means of numerical and analytical methods; comparisons with Monte Carlo simulations are also presented.

Journal Article↗
PubMed2005

Random delays and the synchronization of chaotic maps.

We investigate the dynamics of an array of chaotic logistic maps coupled with random delay times. We report that for adequate coupling strength the array is able to synchronize, in spite of the random delays. Specifically, we find that the synchronized state is a homogeneous steady state, where the chaotic dynamics of the individual maps is suppressed. This synchronization behavior is largely independent of the connection topology and depends mainly on the average number of links per node. We carry out a statistical linear stability analysis that confirms the numerical results and provides a better understanding of the nontrivial roles of random delayed interactions.

Logistic Models↗
PubMed2005

Quasiperiodic route to chaotic dynamics of internet transport protocols.

We show that the dynamics of transmission control protocol (TCP) may often be chaotic via a quasiperiodic route consisting of more than two independent frequencies, by employing a commonly used ns-2 network simulator. To capture the essence of the additive increase and multiplicative decrease mechanism of TCP congestion control, and to qualitatively describe why and when chaos may occur in TCP dynamics, we develop a 1D discrete map. The relevance of these chaotic transport dynamics to real Internet connections is discussed.

Journal Article↗
PubMed1998

Large-scale sprouting of cortical connections after peripheral injury in adult macaque monkeys.

Distributions of thalamic and cortical connections were investigated in four macaque monkeys with long-standing, accidental trauma to a forelimb, to determine whether the growth of new connections plays a role in the reorganization of somatosensory cortex that occurs after major alterations in peripheral somatosensory inputs. In each monkey, microelectrode recordings of cortical areas 3b and 1 demonstrated massive reorganizations of the cortex related to the affected limb. Injections of tracers in area 1 of these monkeys revealed normal patterns of thalamocortical connections, but markedly expanded lateral connections in areas 3b and 1. Thus, the growth of intracortical but not thalamocortical connections could account for much of the reorganization of the sensory maps in cortex.

Amputation, Surgical↗
PubMed2006

Revealing domain structure through linker-scanning analysis of the murine leukemia virus (MuLV) RNase H and MuLV and human immunodeficiency virus type 1 integrase proteins.

Linker-scanning libraries were generated within the 3' terminus of the Moloney murine leukemia virus (M-MuLV) pol gene encoding the connection-RNase H domains of reverse transcriptase (RT) as well as the structurally related M-MuLV and human immunodeficiency virus type 1 (HIV-1) integrase (IN) proteins. Mutations within the M-MuLV proviral vectors were Tn7 based and resulted in 15-bp insertions. Mutations within an HIV-1 IN bacterial expression vector were based on Tn5 and resulted in 57-bp insertions. The effects of the insertions were examined in vivo (M-MuLV) and in vitro (HIV-1). A total of 178 individual M-MuLV constructs were analyzed; 40 in-frame insertions within RT connection-RNase H, 108 in-frame insertions within IN, 13 insertions encoding stop codons within RNase H, and 17 insertions encoding stop codons within IN. For HIV-1 IN, 56 mutants were analyzed. In both M-MuLV and HIV-1 IN, regions are identified which functionally tolerate multiple-linker insertions. For MuLV, these correspond to the RT-IN proteolytic junction, the junction between the IN core and C terminus, and the C terminus of IN. For HIV-1 IN, in addition to the junction between the IN core and C terminus and the C terminus of IN, insertions between the N terminus and core domains maintained integration and disintegration activity. Of the 40 in-frame insertions within the M-MuLV RT connection-RNase H domains, only the three C-terminal insertions mapping to the RT-IN proteolytic junction were viable. These results correlate with deletion studies mapping the domain and subdomain boundaries of RT and IN. Importantly, these genetic footprints provide a means to identify nonessential regions within RT and IN for targeted gene therapy applications.

Amino Acid Sequence↗
PubMed2006

The highly ordered assembly of retinal axons and their synaptic partners is regulated by Hedgehog/Single-minded in the Drosophila visual system.

During development of the Drosophila visual center, photoreceptor cells extend their axons (R axons) to the lamina ganglion layer, and trigger proliferation and differentiation of synaptic partners (lamina neurons) by delivering the inductive signal Hedgehog (Hh). This inductive mechanism helps to establish an orderly arrangement of connections between the R axons and lamina neurons, termed a retinotopic map because it results in positioning the lamina neurons in close vicinity to the corresponding R axons. We found that the bHLH-PAS transcription factor Single-minded (Sim) is induced by Hh in the lamina neurons and is required for the association of lamina neurons with R axons. In sim mutant brains, lamina neurons undergo the first step of differentiation but fail to associate with R axons. As a result, lamina neurons are set aside from R axons. The data reveal a novel mechanism for regulation of the interaction between axons and neuronal cell bodies that establishes precise neuronal networks.

Animals↗
PubMed1989

Hearing aid evaluation using psychoacoustical proximity between Japanese monosyllables.

To facilitate hearing aid selection, a new method was developed to assess the qualitative changes in speech perception with and without a hearing aid. This method utilizes maps of the Japanese monosyllables where the degrees of confusion are represented by distances between the monosyllables. On these maps, perceptual failures of the monosyllables can be simply analyzed by connecting confused stimuli and the corresponding wrong responses. The qualitative characteristics of monosyllable confusion for 53 patients with hearing impairment were comparatively analyzed with and without hearing aids. Results show that this method is useful for describing the qualitative effects of hearing aids on speech perception, and that it thus provides important information for hearing aid selection.

Adolescent↗
PubMedDate not supplied

[Total anomalous infra-cardiac pulmonary venous connection. Value of the color Doppler echocardiography].

A case of total anomalous pulmonary venous connection is described in a newborn. The pulmonary veins join a common trunk entering portal vein below the diaphragm. The pattern of pulmonary venous connections was identified by two-dimensional Doppler color flow-mapping echocardiography. The common pulmonary venous trunk was anastomosed to the left atrium at the age of 3 weeks but the infant died because of pulmonary hypertension and acute renal insufficiency. The Doppler color echocardiography allows a good preoperative evaluation. The spontaneous prognosis being poor, surgical correction is indicated and should be performed early, even for critically ill neonates. Patients who survive to childhood lead active and full lives.

Coronary Vessel Anomalies↗
PubMedDate not supplied

[Inhibitory interactions in neuronal networks including cells of the auditory cortex and the medial geniculate body].

Cross-correlation method was used for revealing effective inhibitory interactions in neural networks containing simultaneously recorded neurons from different loci of auditory cortex (A1) and medial geniculate body (MGB). It was shown that (i) inhibitory connections were "divergent", i. e., one neuron in A1 (MGB) depressed activity of neurons in different loci of A1 and MGB simultaneously; (ii) inputs to inhibitory neuron were "convergent", i.e., one neuron in A1 (MGB) was excited by neurons from different loci of A1 and MGB simultaneously. There were inhibitory neurons which selectively depressed activity of only one neighbouring neuron. The results allow to suggest that the same inhibitory neuron may be involved in afferent and feedback inhibition. We supposed that the principles of organization of inhibitory connections in thalamo-cortical networks underlie the observed exceptions to mapping (tonotopic) principle of organization of receptive fields of A1 and MGB.

Action Potentials↗
PubMed1994

Solution structure of the epsilon-aminohexanoic acid complex of human plasminogen kringle 1.

The solution structure of the human plasminogen kringle 1 domain complexed to the antifibrinolytic drug 6-aminohexanoic acid (epsilon Ahx) was obtained on the basis of 1H-NMR spectroscopic data and dynamical simulated annealing calculations. Two sets of structures were derived starting from (a) random coil conformations and (b) the (mutated) crystallographic structure of the homologous prothrombin kringle 1. The two sets display essentially the same backbone folding (pairwise root-mean-square deviation, 0.15 nm) indicating that, regardless of the initial structure, the data is sufficient to locate a conformation corresponding to an essentially unique energy minimum. The conformations of residues connected to prolines were localized to energetically preferred regions of the Ramachandran map. The Pro30 peptide bond is proposed to be cis. The ligand-binding site of the kringle 1 is a shallow cavity composed of Pro33, Phe36, Trp62, Tyr64, Tyr72 and Tyr74. Doubly charged anionic and cationic centers configured by the side chains of Asp55 and Asp57, and Arg34 and Arg71, respectively, contribute to anchoring the zwitterionic epsilon Ahx molecule at the binding site. The ligand exhibits closer contacts with the kringle anionic centers (approximately 0.35 nm average O...H distance between the Asp55/Asp57 carboxylate and ligand amino groups) than with the cationic ones (approximately 0.52 nm closest O...H distances between the ligand carboxylate and the Arg34/Arg71 guanidino groups). The epsilon Ahx hydrocarbon chain rests flanked by Pro33, Tyr64, Tyr72 and Tyr74 on one side and Phe36 on the other. Dipolar (Overhauser) connectivities indicate that the ligand aliphatic moiety establishes close contacts with the Phe36 and Trp62 aromatic rings. The computed structure suggests that the epsilon Ahx molecule adopts a kinked conformation when complexed to kringle 1, effectively shortening its dipole length to approximately 0.65 nm.

Aminocaproic Acid↗
PubMed2001

Adaptive adjustment of connectivity in the inferior colliculus revealed by focal pharmacological inactivation.

In the midbrain sound localization pathway of the barn owl, a map of auditory space is synthesized in the external nucleus of the inferior colliculus (ICX) and transmitted to the optic tectum. Early auditory experience shapes these maps of auditory space in part by modifying the tuning of the constituent neurons for interaural time difference (ITD), a primary cue for sound-source azimuth. Here we show that these adaptive modifications in ITD tuning correspond to changes in the pattern of connectivity within the inferior colliculus. We raised owls with an acoustic filtering device in one ear that caused frequency-dependent changes in sound timing and level. As reported previously, device rearing shifted the representation of ITD in the ICX and tectum but not in the primary source of input to the ICX, the central nucleus of the inferior colliculus (ICC). We applied the local anesthetic lidocaine (QX-314) iontophoretically in the ICC to inactivate small populations of neurons that represented particular values of frequency and ITD. We measured the effect of this inactivation in the optic tecta of a normal owl and owls raised with the device. In the normal owl, inactivation at a critical site in the ICC eliminated responses in the tectum to the frequency-specific ITD value represented at the site of inactivation in the ICC. The location of this site was consistent with the known pattern of ICC-ICX-tectum connectivity. In the device-reared owls, adaptive changes in the representation of ITD in the tectum corresponded to dramatic and predictable changes in the locations of the critical sites of inactivation in the ICC. Given that the abnormal representation of ITD in the tectum depended on frequency and was likely conveyed directly from the ICX, these results suggest that experience causes large-scale, frequency-specific adjustments in the pattern of connectivity between the ICC and the ICX.

Adaptation, Physiological↗
PubMed1997

Genome cross-referencing and XREFdb: implications for the identification and analysis of genes mutated in human disease.

Comparative genomics approaches and multi-organismal biology are valuable tools for genetic analysis. Cross-species connections between genes mutated in human disease states and homologues in model organisms can be particularly powerful, as model-organism gene function data and experimental approaches can shed light on the molecular mechanisms defective in the disease. We describe a project that is systematically identifying novel expressed sequence tag (EST) sequences that are highly related to genes in model organisms and mapping them to positions on the mouse and human maps. This process effectively cross-references model organism genes with mapped mammalian phenotypes, facilitating the identification of genes mutated in human disease states via the positional candidate approach. A public database, XREFdb (http:@www.ncbi.nlm.nih.gov/XREFdb/), disseminates similarity search, mapping and mammalian phenotype information and increases the rate at which these cross-species connections are established.

Animals↗