bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the Stability of DC Plasma Gun Operating with Ar‐He‐H2 Gas Mixtures
Authors: JANISSON STEPHANE , VARDELLE ARMELLE , COUDERT JEAN‐FRANCOIS , FAUCHAIS PIERRE , MEILLOT ERICK
Published: February 2006

ABSTRACT: The plasma‐forming gas composition is one of the parameters of a plasma spray process which can be adjusted by the operator to obtain deposits with the required properties. The gas composition affects the heat and momentum transfer to the particles injected in the flow, but also the working and stability of the plasma gun. This paper presents an investigation of the effect of gas composition and flow rate, and arc current on arc instabilities. The study was carried out for various ternary gas mixtures of argon, helium and hydrogen. The movement of the arc root attachment spot on the anode wall was characterized from the time‐evolution of arc voltage and the fluctuations of the plasma jet from the velocity fluctuations. The experiments were carried out with a new and a worn anode. The characteristic frequency of arc fluctuations was correlated in terms of the primary parameters of the spray process and gas mixture properties.
SYSTEMATIZATION OF GENERALIZED ANALYTICAL EXPRESSIONS FOR CALCULATING CHARACTERISTICS OF CASCADED ARCS
Authors: BUBLIEVSKY ALEXANDER F. , SHARAKHOVSKY LEONID I. , YAS'KO OLEG I.
Published: February 2006

ABSTRACT: A classification of analytical dimensionless equations for characteristics of cascaded electric arcs is proposed. It is based on the distinction in forms of functions specification and on the difference in characteristic value of quantities. The variety of the equations forms is brought into a system that facilitates calculation of arcs characteristics. The obtained equations coincide with results of other authors in some particular cases.
Formation of Jets and Ejection under Metastable Plasma Conditions
Authors: EMELIN SERGEI E. , KOVSHIK ALEXANDER P. , RJUMTSEV EVGENIY I.
Published: February 2006

ABSTRACT: In the paper a description and photos of non‐stationary forms of erosional discharge in a radial slot are given that demonstrate the process of formation of jets and ejection of current loops. Rise of new found peculiarities of plasma jets, analogous to that discovered earlier in a capillary discharge, is explained by appearance of non‐equilibrium dynamic state, having a marked direction of transport wave flux, and plasma anisotropy in metastable plasma.
Chance Favors the Prepared Genome
Authors: CAPORALE LYNN HELENA
Published: February 2006

ABSTRACT: Most descriptions of mutation have emphasized its negative consequences, and randomness with respect to biological function. This book seeks to balance the discussion by emphasizing mechanisms that both diversify the genome and increase the probability that a genome's descendants will survive. This chapter provides a framework for, and overview of, the diverse contributions to this book; these contributions will be stimulating companions, well into the 21st Century, as we work to comprehend the information contained in genomic databases. Genomes that encode “better” amino acid sequences are at a selective advantage. Genomes that generate diversity also are at an advantage to the extent that they can navigate efficiently through the space of possible sequence changes. a Biochemical systems that tend to increase the ratio of useful to destructive genetic change may harness preexisting information (horizontal gene transfer, DNA translocation and/or DNA duplication), focus the location, timing, and extent of genetic change, adjust the dynamic range of a gene's activity, and/or sample regulatory connections between sites distributed across the genome. Rejecting entirely random genetic variation as the substrate of genome evolution is not a refutation, but rather provides a deeper understanding, of the theory of natural selection of Darwin and Wallace. The fittest molecular strategies survive, along with descendants of the genomes that encode them.
Genome System Architecture and Natural Genetic Engineering in Evolution
Authors: SHAPIRO JAMES A.
Published: February 2006

ABSTRACT:Molecular genetics teaches three lessons relevant to the nature of genetic change during evolution: (1) Genomes are organized as hierarchies of composite systems (multidomain protein‐coding sequences; functional loci made up of regulatory, coding, processing, and intervening sequences; and multilocus regulons and replicons) interconnected and organized into specific “system architectures” by repetitive DNA elements. (2) Genetic change often occurs via natural genetic engineering systems (cellular biochemical functions, such as recombination complexes, topoisomerases, and mobile elements, capable of altering DNA sequence information and joining together different genomic components). (3) The activity of natural genetic systems is regulated by cellular control circuits with respect to the timing, activity levels, and specificities of DNA rearrangements (e.g., adaptive mutation, Ty element mobility, and P factor insertions). These three lessons provide plausible molecular explanations for the episodic, multiple, nonrandom DNA rearrangements needed to account for the evolution of novel genomic system architectures and complex multilocus adaptations. This molecular genetic perspective places evolutionary change in the biologically responsive context of cellular biochemistry.
Involvement of Gene Products in Bacterial Evolution
Authors: ARBER WERNER
Published: February 2006

ABSTRACT: Three strategies of different quality contribute in parallel to the natural formation of genetic variants in bacteria: (1) small local alterations of DNA sequences; (2) recombinational reshuffling of segments of the genome; and (3) acquisition of DNA sequences by horizontal gene transfer. Key enzymes involved in these processes often act as variation generators by making use of structural flexibilities of biological macromolecules and of the effect of random encounter. In the theory of molecular evolution, genetic determinants of variation generators as well as of modulators of the frequency of genetic variation are defined as evolutionary genes. This postulate is consistent with the notion that spontaneous mutagenesis is in general not adaptive and that the direction of evolution depends on natural selection exerted on populations of genetic variants.
Palindromic DNA and Genome Stability: Further Studiesa
Authors: LEWIS SUSANNA , AKGÜN ERCAN , JASIN MARIA
Published: February 2006

ABSTRACT: Unusual DNA structures promote genetic instability. One such example is hairpin DNA, which can form from palindromic sequences and triplet repeats, and is also a characteristic intermediate in V(D)J recombination. We previously found that a large 15.3‐kb palindrome that was introduced as a transgene into the mouse germline was highly unstable. Although it could be transmitted, the transgene was found to be rearranged in up to 56% of the progeny, and rearrangement events often involved deletion at the center of symmetry. Here, the fine structure of centrally deleted palindromes was sampled by analysis of recombinant junctions isolated from testes DNA, providing further evidence for a model, previously proposed, that accounts for such deletions on the basis of a hairpin‐tip nicking activity. In addition to central deletions, gene conversion events were also elevated in the transgenic palindrome. We have now analyzed instability in two mouse sublines in which (as a result of inversion) the transgenic palindrome had been shortened to 4.2 kb. In these sublines, the transgene was still subject to both rearrangement and gene conversion events at a high frequency, similar to the original 15.3‐kb palindrome. Recombination was not limited to the sequences constituting the inverted repeat, but was seen to include sequences lying outside the palindrome. As discussed, the salient feature in all of these observations, a high level of genetic change associated with palindromic DNA, underscores the significance of hairpin DNA and hairpin‐tip nicking in genome stability.
Evolutionary Genomics of Vertebrates and Its Implications
Authors: D'ONOFRIO GIUSEPPE , JABBARI KAMEL , MUSTO HÉCTOR , ALVAREZ‐VALIN FERNANDO , CRUVEILLER STEPHANE , BERNARDI GIORGIO
Published: February 2006

ABSTRACT: The discovery that the vertebrate genomes of warm‐blooded vertebrates are mosaics of isochores, long DNA segments homogeneous in base composition, yet belonging to families covering a broad spectrum of GC levels, has led to two major observations. The first is that gene density is strikingly non‐uniform in the genome of all vertebrates, gene concentration increasing with increasing GC levels. (Although the genomes of cold‐blooded vertebrates are characterized by smaller compositional heterogeneities than those of warm‐blooded vertebrates and high GC levels are not attained, their gene distribution is basically similar to that of warm‐blooded vertebrates.) The second observation is that the GC‐richest and gene‐richest isochores underwent a compositional transition (characterized by a strong increase in GC level) between cold‐ and warm‐blooded vertebrates. Evidence to be discussed favors the idea that this compositional transition and the ensuing highly heterogeneous compositional pattern was due to, and was maintained by, natural selection.
The Distribution of Rates of Spontaneous Mutation over Viruses, Prokaryotes, and Eukaryotes
Authors: DRAKE JOHN W.
Published: February 2006

ABSTRACT: Although mutation has chaotic aspects, spontaneous mutation rates assume certain characteristic values when expressed per genome per genome duplication. The rate among lytic RNA viruses is roughly 1, while the rate among retroelements is roughly 0.2. The rate among viral and cellular microbes with DNA chromosomes is close to 0.0034. Mutation rates among higher eukaryotes, estimated from specific‐locus studies, vary greatly. Most of this variation can be suppressed if the rates are expressed per cell division instead of per sexual generation, and if the genome size is taken to be only a little larger than the sum of the protein‐encoding sequences; then, the mutation rate is roughly 0.01. The reasons for different characteristic mutation rates among different organism groups remain mysterious and pose a substantial challenge to students of evolution.
Fidelity of Retrotransposon Replication
Authors: GABRIEL ABRAM , MULES EMILIE H.
Published: February 2006

ABSTRACT: Ty1, the genetically tractable retrotransposable element found in the yeast Saccharomyces cerevisiae, closely resembles vertebrate retroviruses both in structure and in mechanism of replication. By direct sequence analysis, we examined the rate and spectrum of new mutations appearing during a single cycle of Ty1 replication. The rate of new mutations was comparable to those seen for replicating retroviruses. All observed changes were base substitutions, and their location suggested that template ends may be hot spots for generating these mutations. To test this, we developed methods to examine, at the nucleotide level, the end structure of the expected Ty1 replication intermediates. Our results demonstrate that Ty1 reverse transcriptase can add terminal non‐templated bases in vivo during each step in replication. Furthermore, Ty1 RNAse H creates multiple template ends by imprecisely cleaving RNA. This expands the range of sites of subsequent non‐templated base addition. Finally, on reaching template ends, Ty1 reverse transcriptase can strand transfer to inappropriate templates. Taken together, these mutagenic mechanisms may influence the evolution of particular regions of the Ty1 genome and serve as a mechanism to regulate the overall level of Ty1 transposition in its host cell.
DNA‐Directed Mutations: Leading and Lagging Strand Specificity
Authors: SINDEN RICHARD R. , HASHEM VERA I. , ROSCHE WILLIAM A.
Published: February 2006

ABSTRACT: The fidelity of replication has evolved to reproduce B‐form DNA accurately, while allowing a low frequency of mutation. The fidelity of replication can be compromised, however, by defined order sequence DNA (dosDNA) that can adopt unusual or non B‐DNA conformations. These alternative DNA conformations, including hairpins, cruciforms, triplex DNAs, and slipped‐strand structures, may affect enzyme‐template interactions that potentially lead to mutations. To analyze the effect of dosDNA elements on spontaneous mutagenesis, various mutational inserts containing inverted repeats or direct repeats were cloned in a plasmid containing a unidirectional origin of replication and a selectable marker for the mutation. This system allows for analysis of mutational events that are specific for the leading or lagging strands during DNA replication in Escherichia coli. Deletions between direct repeats, involving misalignment stabilized by DNA secondary structure, occurred preferentially on the lagging strand. Intermolecular strand switch events, correcting quasipalindromes to perfect inverted repeats, occurred preferentially during replication of the leading strand.
Immunoglobulin Switch Recombination May Occur by a DNA End‐Joining Mechanisma
Authors: KENTER AMY , WUERFFEL ROBERT
Published: February 2006

ABSTRACT: Immunoglobulin switch recombination is a specialized recombination event that occurs exclusively in B lymphocytes and is focused on tandemly repetitive DNA sequences called switch regions. Switch recombination occurs as an intrachromosomal deletion event in which the deleted genetic material is excised as a circle. Although the developmental profile of this recombination event is well characterized, the underlying mechanism for switch recombination is poorly understood. Recent studies detected the presence of double strand breaks in switch DNA and the dependency of switching on the Ku and DNA‐dependent protein kinase proteins which are involved in repair of double strand breaks by nonhomologous end‐joining. Taken together these findings strongly suggest that switch recombination is a specialized recombination system that occurs through a DNA end‐joining mechanism.
Speciation of Cone Snails and Interspecific Hyperdivergence of Their Venom Peptides: Potential Evolutionary Significance of Intronsa
Authors: OLIVERA BALDOMERO M. , WALKER CRAIG , CARTIER G. EDWARD , HOOPER DAVID , SANTOS AMEURFINA D. , SCHOENFELD ROBERT , SHETTY RESHMA , WATKINS MAREN , BANDYOPADHYAY PRADIP , HILLYARD DAVID R.
Published: February 2006

ABSTRACT:All 500 species of cone snails (Conus) are venomous predators. From a biochemical/genetic perspective, differences amongConusspecies may be based on the 50‐200 different peptides in the venom of each species. Venom is used for prey capture as well as for interactions with predators and competitors. The venom of every species has its own distinct complement of peptides. Some of the interspecific divergence observed in venom peptides can be explained by differential expression of venom peptide superfamilies in different species and of peptide superfamily branching in variousConuslineages into pharmacologic groups with different targeting specificity. However, the striking interspecific divergence of peptide sequences is the dominant factor in the differences observed between venoms. The small venom peptides (typically 10‐35 amino acids in length) are processed from larger prepropeptide precursors (ca. 100 amino acids). If interspecific comparisons are made between homologous prepropeptides, the three different regions of aConuspeptide precursor (signal sequence, pro‐region, mature peptide) are found to have diverged at remarkably different rates. Analysis of synonymous and nonsynonymous substitution rates for the different segments of a prepropeptide suggests that mutation frequency varies by over an order of magnitude across the segments, with the mature toxin region undergoing the highest rate. The three sections of the prepropeptide which exhibit apparently different mutation rates are separated by introns. This striking segment‐specific rate of divergence ofConusprepropeptides suggests a role for introns in evolution: exons separated by introns have the potential to evolve very different mutation rates. Plausible mechanisms that could underlie differing mutational frequency in the different exons of a gene are discussed.
Mechanisms of Genome‐Wide Hypermutation in Stationary Phasea
Authors: LOMBARDO MARY‐JANE , TORKELSON JOEL , BULL HAROLD J. , McKENZIE GREGORY J. , ROSENBERG SUSAN M.
Published: February 2006

ABSTRACT: Stationary‐phase mutation (a subset of which was previously called adaptive mutation) occurs in apparently nondividing, stationary‐phase cells exposed to a nonlethal genetic selection. In one experimental system, stationary‐phase reversion of an Escherichia coli F′‐borne lac frameshift mutation occurs by a novel molecular mechanism that requires homologous recombination functions of the RecBCD system. Chromosomal mutations at multiple loci are detected more frequently in Lac+ stationary‐phase revertants than in cells that were also exposed to selection but did not become Lac+. Thus, mutating cells represent a subpopulation that experiences hypermutation throughout the genome. This paper summarizes current knowledge regarding stationary‐phase mutation in the lac system. Hypotheses for the mechanism of chromosomal hypermutation are discussed, and data are presented that exclude one hypothetical mechanism in which chromosomal mutations result from Hfr formation.
Evolution of DNA Organization in Hypotrichous Ciliatesa
Authors: PRESCOTT DAVID M.
Published: February 2006

ABSTRACT: Profound changes have been introduced into the germline (micronuclear) and somatic (macronuclear) genomes of hypotrichous ciliates during evolution. First, multiple, short, unique, noncoding sequences, called IESs, have been inserted into micronuclear genes. IESs are spliced out of each gene, and the gene segments, called MDSs, are ligated during conversion of the micronuclear genome to a macronuclear genome after cell mating. The IESs in a particular gene can change dramatically in number, position, length, and sequence during speciation. Once inserted, IESs can shift along the DNA of a gene 1 or 2 bp at a time by a mutational mechanism that does not alter the coding sequence of the gene. Second, the MDSs in the same genes have been rearranged into random or nonrandom, scrambled disorder. The origin of nonrandom scrambling patterns can be explained by a model of simultaneous insertion of multiple IESs into a germline gene during evolution. Subsequent recombinations among the IESs may change the MDS arrangement from a nonrandomly scrambled to a randomly scrambled pattern, including inversions of MDSs. Third, during the conversion of a micronucleus to a macronucleus after cell mating, MDSs are ligated in the unscrambled, orthodox order in association with IES excision, and the genes are then removed from the chromosomes as individual, short DNA molecules. These gene‐size molecules are amplified many‐fold to produce a mature macronucleus. All of these phenomena attest to a remarkable fluidity of the hypotrich genome both over evolutionary time and in the conversion of a germline genome to a somatic genome. The significance of this fluidity for the life and evolution of these organisms is still obscure. Recombination among IESs could shuffle MDSs and facilitate faster evolution of new genes.
Elucidating Sequence Codes: Three Codes for Evolution
Authors: TRIFONOV EDWARD N.
Published: February 2006

ABSTRACT: The sequences are related to evolution in several ways. First, they carry traces of a distant past. Two sequence features point to the earliest sequence organization. The universal hidden GCU‐periodical pattern in mRNA suggests the earliest codons: GCU and its nine‐point‐change derivatives. They code for seven amino acids that by several criteria are also the oldest. Together it makes the earliest form of the triplet code, still recognizable in the extant sequences. Another feature present in the sequences, apparently, since separation of prokaryotes and eukaryotes, is hidden genome segmentation. Both protein‐coding and noncoding sequences appear to have been formed by fusion of standard size units, about 360 bp (120 aa) in eukaryotes and 450 bp (150 aa) in prokaryotes. Presumably, the units have been functioning at some stage of evolution as autonomous single‐gene size elements. There are sequence designs that promote evolution. One such design suitable for fast adaptation is the tandem repetition of identical sequences, so that their copy numbers in the repeat arrays would modulate (tune) the expression of nearby genes. The tandem repeat expansion diseases illustrate this mechanism in a dramatic way: overtuning of the respective gene expression leads to the disease.
Otolith Ocular Reflex Function of the Tangential Nucleus in Teleost Fish
Authors: SUWA HIROSHI , GILLAND EDWIN , BAKER ROBERT
Published: February 2006

Abstract: In teleost fish, the tangential nucleus can be identified as a compact, separate cell group lying ventral to the VIIIth nerve near the middle of the vestibular complex. Morphological analysis of larval and adult hindbrains utilizing biocytin and fluorescent tracers showed the tangential nucleus to be located entirely within rhombomeric segment 5 with all axons projecting into the contralateral MLF. Combined single‐cell electrophysiology and morphology in alert goldfish found three classes of neurons whose physiological sensitivity could be readily correlated with rotational axes about either the anterior (45°), posterior (135°), or horizontal (vertical axis) semicircular canals. Tangential neurons could be distinguished from those in semicircular‐canal specific subnuclei by an irregular, spontaneous background of 10‐15 sp/s and sustained static sensitivity after ±4° head displacements. Each axis‐specific tangential subtype terminated appropriately onto oculomotor subnuclei responsible for either vertical, torsional, or horizontal eye movements and, in a few cases, axon collaterals descended in the MLF toward the spinal cord. We hypothesize, therefore, that the tangential nucleus consists of 3 axis‐specific phenotypes that process gravitoinertial signals largely responsible for controlling oculomotor function, but that also in part, maintain body posture.
Miniature EPSPs and Sensory Encoding in the Primary Afferents of the Vestibular Lagena of the Toadfish, Opsanus tau
Authors: LOCKE RACHEL , VAUTRIN JEAN , HIGHSTEIN STEPHEN
Published: February 2006

Abstract: The synaptic activity transmitted from vestibular hair cells of the lagena to primary afferent neurons was recorded in vitro using sharp, intracellular micro‐electrodes. At rest, the activity was composed of miniature excitatory postsynaptic potentials (mEPSPs) at frequencies from 5 to 20/s and action potentials (APs) at frequencies between 0 and 10/s. mEPSPs recorded from a single fiber displayed a large variability. For mEPSPs not triggering APs, amplitudes exhibited an average coefficient of variance (CV) of 0.323 and rise times an average CV of 0.516. APs were only triggered by mEPSPs with larger amplitudes (estimated 4‐6 mV) and/or steeper maximum rate of rise (10.9 mV/ms, ± 3.7 SD, n= 4 experiments) compared to (3.50 mV/ms, ±0.07 SD, n= 6 experiments) for nontriggering mEPSPs. The smallest mEPSPs showed a fast rise time (0.99 ms between 10% and 90% of peak amplitude) and limited variability across fibers (CV: 0.18) confirming that they were not attenuated signals, but rather represented single‐transmitter discharges (TDs). The mEPSP amplitude and rise‐time relationship suggests that many mEPSPs represented several, rather than a single pulse of secretion or TDs. According to the estimated overall TD frequency, the coincidence of TDs contributing to the same mEPSP were not statistically independent, indicating a positive interaction between TDs that is reminiscent of the way subminiature signals group to form minature signals at the neuromuscular junction. Depending on the duration and intensity of efferent stimulation, a complete block of AP initiation occurred either immediately or after a delay of a few seconds. Efferent stimulation did not significantly change AP threshold level, but abruptly decreased mEPSP frequency to a near‐complete block that followed the block of APs. Maximum mEPSP rate of rise decreased during, and recovered progressively after, efferent stimulation. After termination of efferent stimulation, mEPSP amplitude did not recover instantly and for a few seconds the amplitude distribution of synaptic events showed fewer large‐amplitude events than during the control period. This confirms that mEPSP amplitude and rate of rise properties, which are critical for triggering afferent APs, are modified by efferent activity. The depression of afferent AP firing during efferent stimulation corresponded to a decrease in mEPSP frequency and, to a lesser extent, a decrease in mEPSP amplitude and rate of rise, suggesting, a decrease in the level of interaction among TDs contributing to a mEPSP.
Signal Processing Related to the Vestibulo‐Ocular Reflex during Combined Angular Rotation and Linear Translation of the Head
Authors: MCCREA ROBERT A. , CHEN‐HUANG CHIJU
Published: February 2006

Abstract: The contributions of vestibular nerve afferents and central vestibular pathways to the angular (AVOR) and linear (LVOR) vestibulo‐ocular reflex were studied in squirrel monkeys during fixation of near and far targets. Irregular vestibular afferents did not appear to be necessary for the LVOR, since when they were selectively silenced with galvanic currents the LVOR was essentially unaffected during both far‐ and near‐target viewing. The linear translation signals generated by secondary AVOR neurons in the vestibular nuclei were, on average, in phase with head velocity, inversely related to viewing distance, and were nearly as strong as AVOR‐related signals. We suggest that spatial‐temporal transformation of linear head translation signals to angular eye velocity commands is accomplished primarily by the addition of viewing distance multiplied, centrally integrated, otolith regular afferent signals to angular VOR pathways.
Otolith Processing in the Deep Cerebellar Nuclei
Authors: BÜTTNER U. , GLASAUER S. , GLONTI L. , KLEINE J. F. , SIEBOLD C.
Published: February 2006

Abstract: To investigate the otolith contribution to the responses of “vestibular only” neurons in the rostral fastigial nucleus (FN), single‐unit activity was recorded in the alert monkey with the head fixed during static and dynamic stimulation (± 15 deg, 0.06‐1.4 Hz) around an earth‐fixed horizontal axis. Head orientation could be altered allowing for roll, pitch, and intermediate planes of orientation. For the vast majority of neurons a response vector orientation (RVO) with an optimal response and a null‐response at a head orientation 90 deg apart could be determined. Presumably more than 30% of the vestibular only neurons had an otolith input, as indicated by responses to static tilt, head‐position‐related activity, large phase changes (> 100 deg) of neuronal activity between 0.06 and 1.4 Hz, changes of the RVO at different frequencies and complex responses (spatio‐temporal convergence). Thus, neurons in FN reflecting an otolith or a combined canal‐otolith input are much more common than up to now thought. Vestibular‐only neurons are most likely involved in vestibulospinal mechanisms. Their precise functional role has yet to be determined.
Control of Spatial Orientation of the Angular Vestibulo‐Ocular Reflex by the Nodulus and Uvula of the Vestibulocerebellum
Authors: SHELIGA BORIS M. , YAKUSHIN SERGEI B. , SILVERS ADAM , RAPHAN THEODORE , COHEN BERNARD
Published: February 2006

Abstract: Eye velocity produced by the angular vestibulo‐ocular reflex (aVOR) tends to align with the summed vector of gravity and other linear accelerations [gravito‐inertial acceleration (GIA)]. Defined as “spatial orientation of the aVOR,” we propose that it is controlled by the nodulus and uvula of the vestibulocerebellum. Here, electrical stimulation, injections of the GABAA agonist, muscimol, and single‐cell recordings were utilized to investigate this spatial orientation. Stimulation, injection, and recording sites in the nodulus were determined in vivo by MRI and verified in histological sections. MRI proved to be a sensitive, reliable way to localize electrode placements. Electrical stimulation at sites in the nodulus and sublobule d of the uvula produced nystagmus whose slow‐phase eye‐velocity vectors were either head centric or spatially invariant. When head centric, the eye velocity vector remained within ±45° of the vector obtained with the animal upright, regardless of head position with respect to gravity. When spatially oriented, the vector remained relatively constant in space in one on‐side position, with respect to the vector determined with the animal upright. A majority of induced movements from the nodulus were spatially oriented. Spatially oriented movements were generally followed by after‐nystagmus, which had the characteristics of optokinetic after‐nystagmus (OKAN), including orientation to the GIA. After muscimol injections, horizontal‐to‐vertical cross‐coupling was lost or reduced during OKAN in tilted positions. This supports the hypothesis that the nodulus mediates yaw‐to‐vertical or roll cross‐coupling. The injections also shortened the yaw‐axis time constant and produced contralateral horizontal spontaneous nystagmus, whose velocity varied as a function of head position with regard to gravity. Nodulus units were tested with static head tilt, sinusoidal oscillation around a spatial horizontal axis with the head in different orientations relative to the pitching plane, and off‐vertical axis rotation (OVAR). The direction of the response vectors of the otolith‐recipient units in the nodulus, determined from static and/or dynamic head tilts, were confirmed by OVAR. These vector directions lay close to the planes of the vertical canals in 7/10 units; many units also had convergent input from the vertical canals. It is postulated that the orientation properties of the aVOR result from a transfer of otolith input regarding head tilt along canal planes to canal‐related zones of the nodulus. In turn, Purkinje cells in these zones project to vestibular nuclei neurons to control eye velocity around axes normal to these same canal planes.
Characteristics of the VOR in Response to Linear Acceleration
Authors: PAIGE GARY D. , SEIDMAN SCOTT H.
Published: February 2006

Abstract: The primate linear VOR (LVOR) includes two forms. First, eye‐movement responses to translation [e.g., horizontal responses to interaural (IA) motion] help maintain binocular fixation on targets, and therefore a stable bifoveal image. The translational LVOR is strongly modulated by fixation distance, and operates with high‐pass dynamics (>1 Hz). Second, other LVOR responses occur that cannot be compensatory for translation and instead seem compensatory for head tilt. This reflects an otolith response ambiguity‐that is, an inability to distinguish head translation from head tilt relative to gravity. Thus, ocular torsion is appropriately compensatory for head roll‐tilt, but also occurs during IA translation, since both stimuli entail IA acceleration. Unlike the IA‐horizontal response, IA torsion behaves with low‐pass dynamics (with respect to “tilt”), and is uninfluenced by fixation distance. Interestingly, roll‐tilt, like IA translation, also produces both horizontal (a translational reflex) and torsional (a tilt reflex) responses, further emphasizing the ambiguity problem. Early data from subjects following unilateral labyrinthectomy, which demonstrates a general immediate decline in translational LVOR responses, are also presented, followed by only modest recovery over several months. Interestingly, the usual high‐pass dynamics of these reflexes shift to an even higher cutoff. Both eyes respond roughly equally, suggesting that unilateral otolith input generates a binocularly symmetric LVOR.
Cross‐Striolar and Commissural Inhibition in the Otolith System
Authors: UCHINO Y. , SATO H. , KUSHIRO K. , ZAKIR M. , IMAGAWA M. , OGAWA Y. , KATSUTA M. , ISU N.
Published: February 2006

Abstract: Neural connections from the saccular and utricular nerves to the ipsilateral vestibular neurons and the commissural effects were studied by using intracellular recordings of excitatory (E) and inhibitory (I) postsynaptic potentials (PSPs) in vestibular neurons of cats after focal stimulation of the saccular and the utricular maculae. Neural circuits from the maculae to vestibular neurons, termed crossstriolar inhibition, may provide a mechanism for increasing the sensitivity to linear acceleration and tilt of the head. It was examined whether secondary vestibular neurons activated by an ipsilateral otolith organ received a commissural inhibition from a contralateral otolith organ that occupied the same geometric plane. Results suggest that utricular‐activated vestibular neurons receiving commissural inhibition may provide a mechanism for increasing the sensitivity to horizontal linear acceleration and tilt of the head. The commissural inhibition of the saccular system was much weaker than that of the utricular system.
Human Ocular Counterrolling During Roll‐Tilt and Centrifugation
Authors: MacDOUGALL H. G. , CURTHOYS I. S. , BETTS G. A. , BURGESS A. M. , HALMAGYI G. M.
Published: February 2006

Abstract: To test a hypothesis about how otoliths resolve roll‐tilts from translations, we measured human ocular torsion position [ocular counterrolling (OCR)] to maintained linear acceleration stimuli. All subjects (n=8) were tested in two conditions where the same magnitude of shear along an interaural axis was generated in one of two ways: either by roll‐tilt on a tilt‐chair in a 1‐g environment, or by centripetal linear acceleration during constant velocity rotation 1 m from the axis of rotation on a fixed‐chair human centrifuge. The interaural shear to the otoliths was the same for these two conditions, but the dorsoventral shear was different and for all eight subjects the OCR on the centrifuge was significantly greater than the torsion on the tilt‐chair, although the resultant angle was in fact smaller on the centrifuge than on the tilt‐chair. The results confirm that dorsoventral shear is important for determining OCR. The otoliths may resolve potential stimulus ambiguities between tilts and translations by virtue of the different patterns of interaural and dorsoventral shear that these stimuli generate.
Canal and Otolith Afferent Activity Underlying Eye Velocity Responses to Pitching While Rotating
Authors: RAPHAN T. , DAI M. , MARUTA J. , WAESPE W. , HENN V. , SUZUKI J.‐I. , COHEN B.
Published: February 2006

Abstract: Pitching the head while rotating (PWR) combines periodic activation of the semicircular canals and the otoliths to generate pitch and roll eye deviations and continuous horizontal nystagmus. Monkeys were tested after individual pairs of semicircular canals were plugged and single units were recorded in the vestibular nerve while the animals were sinusoidally pitched 20‐40 deg about a spatial horizontal axis with 5‐ and 16‐s periods and simultaneously rotated about a spatial vertical axis at 30‐120 deg/s. As previously shown, the steady‐state horizontal response disappeared after plugging the vertical semicircular canals, but was maintained when the lateral canals were plugged. When the left anterior and right posterior canal (LARP) pair was left intact, the steady‐state response depended on the axis about which the pitching took place. When the axis was normal to the LARP plane, there was no steady‐state response. When the pitching axis was perpendicular to the LARP normal, the response was maximal. Firing rates of otolith units were approximately in phase with pitch position, and the addition of rotation about a vertical axis did not change the response. Lateral canal units did not have a steady‐state modulation during pitch or constant velocity rotation. During PWR, they oscillated at twice the pitch frequency. This corresponded to the frequency at which the canal was maximally activated as it aligned with the plane of rotation. The amplitude of modulation increased proportionally to rotational velocity, but the phase remained the same. These characteristics were unchanged during roll while rotating (RWR), which induces little continuous nystagmus. Anterior and posterior canal units were maximally excited near pitch‐velocity maxima and minima, respectively, during pure pitching. During PWR, however, the phases of both components simultaneously shifted toward each other and toward being in phase with otolith units. The peak excitation tended toward a forward‐pitch position when the rotation was to the ipsilateral side, and toward a backward pitch position when the rotation was to the contralateral side. With 120‐deg/s rotation during a 16‐s pitch period, the phase difference between anterior and posterior canal units was as small as 17 deg. These data support the postulate that the correlation between vertical canal and otolith units is the critical factor in generating continuous unidirectional horizontal nystagmus during PWR.
Directional Abnormalities of Vestibular and Optokinetic Responses in Cerebellar Disease
Authors: WALKER MARK F. , ZEE DAVID S.
Published: February 2006

Abstract: Directional abnormalities of vestibular and optokinetic responses in patients with cerebellar degeneration are reported. Three‐axis magnetic search‐coil recordings of the eye and head were performed in eight cerebellar patients. Among these patients, examples of directional cross‐coupling were found during (1) high‐frequency, high‐acceleration head thrusts; (2) constant‐velocity chair rotations with the head fixed; (3) constant‐velocity optokinetic stimulation; and (4) following repetitive head shaking. Cross‐coupling during horizontal head thrusts consisted of an inappropriate upward eye‐velocity component. In some patients, sustained constant‐velocity yaw‐axis chair rotations produced a mixed horizontal‐torsional nystagmus and/or an increase in the baseline vertical slow‐phase velocity. Following horizontal head shaking, some patients showed an increase in the slow‐phase velocity of their downbeat nystagmus. These various forms of cross‐coupling did not necessarily occur to the same degree in a given patient; this suggests that different mechanisms may be responsible. It is suggested that cross‐coupling during head thrusts may reflect a loss of calibration of brainstem connections involved in the direct vestibular pathways, perhaps due to dysfunction of the flocculus. Cross‐coupling during constant‐velocity rotations and following head shaking may result from a misorientation of the angular eye‐velocity vector in the velocity‐storage system. Finally, responses to horizontal optokinetic stimulation included an inappropriate torsional component in some patients. This suggests that the underlying organization of horizontal optokinetic tracking is in labyrinthine coordinates. The findings are also consistent with prior animal‐lesion studies that have shown a role for the vestibulocerebellum in the control of the direction of the VOR.
Vestibular‐Pursuit Interactions: Gaze‐Velocity and Target‐Velocity Signals in the Monkey Frontal Eye Fields
Authors: FUKUSHIMA KIKURO , FUKUSHIMA JUNKO , SATO TOSHIKAZU
Published: February 2006

Abstract: Visual information about a moving object is obtained by accurate tracking with the eyes using the smooth pursuit system, which must interact with the vestibular system during head movement. Such pursuit‐vestibular interactions require calculation of gaze (i.e., eye in space) in order to match eye velocity in space to actual target velocity, using vestibular, retinal‐image velocity, and eye‐velocity information. To understand the role the frontal eye fields (FEFs) play in pursuit‐vestibular interactions, we examined responses of pursuit‐related neurons near the arcuate sulcus in head‐stabilized monkeys during visual tracking tasks that dissociate eye movement in the orbit from that in space. The activity of the majority of pursuit‐related neurons was related to gaze velocity. They also responded to passive body rotation in complete darkness. When the monkeys fixated the stationary target, similar modulation was observed, reflecting the velocity signal of a second test target. Muscimol infusion into the FEF pursuit areas severely impaired smooth gaze tracking. These results suggest that the region near the arcuate sulcus coordinates its various inputs to provide signals for target velocity in space and accurate gaze‐velocity command during pursuit‐vestibular interactions.
Short‐Latency Visual Stabilization Mechanisms that Help to Compensate for Translational Disturbances of Gaze
Authors: MILES F. A.
Published: February 2006

Abstract: Recent studies in primates have revealed short‐latency visual tracking mechanisms that help to stabilize the eyes during translational disturbances of the observer, and so operate as backups to otolith‐mediated vestibulo‐ocular reflexes. One such mechanism generates version eye movements to help stabilize gaze when the moving observer looks off to one side, utilizing binocular disparity to help single out the images in the plane of fixation (ocular following). Two others generate vergence eye movements to help maintain binocular alignment on objects that lie ahead: one responds to the radial patterns of optic flow (radial‐flow vergence) and the other to the changes in binocular parallax (disparity vergence). Accumulating evidence suggests that, despite their short latency, all are mediated by the medial superior temporal area of cortex.
Replication of Passive Whole‐Body Linear Displacements from Inertial Cues: Facts and Mechanisms
Authors: GRASO R. , GLASAUER S. , GEORGE‐FRANÇOIS P. , ISRAËL I.
Published: February 2006

Abstract: Using path integration, normal subjects should be able to compute the distance of a traveled path even from the sole inertial sensory input. Blindfolded subjects were submitted to a passive linear forward displacement along 2 to 10 m. Their task was to replicate the traveled distance, still blindfolded, by driving the vehicle they were seated upon using a joystick that controlled linear speed.

Subjects replicated both the length and the velocity profile of the passive travel, suggesting that a dynamic record of experienced motion is stored in memory. Even when the replication of passive motion dynamics was made impossible, the subjects could still replicate the displacement.

The results are explained by a dynamic feedback model that performs a running comparison between the perceived instantaneous displacement of the ongoing motion and the displacement derived from a spatiotemporal record of perceived passive motion. A multimodal acceleration‐related sensory input is transformed into a displacement‐related perception through double time‐integration.
The Ins and Outs of Caveolar Signaling: m2 Muscarinic Cholinergic Receptors and eNOS Activation versus Neuregulin and ErbB4 Signaling in Cardiac Myocytesa
Authors: FERON OLIVIER , ZHAO YOU‐YANG , KELLY RALPH A.
Published: February 2006

Abstract: Endothelial cells constitutively express the NOS isoform eNOS, which generates NO in response to specific extracellular signals to regulate vascular smooth muscle tone, vascular permeability, and platelet adhesion, among other actions. In addition to coronary vascular and endocardial endothelium, both atrial and ventricular myocytes express eNOS, the activation of which is also dependent on specific intracellular and extracellular signals. eNOS is targeted in cardiac myocytes to caveolae in plasma membranes and, in the case of cardiac myocytes, possibly T‐tubular membranes as well. eNOS targeting to caveolae in cardiac myocytes requires co‐translational myristoylation and subsequent palmitoylation for efficient targeting of the enzyme to the specialized lipid microdomains characteristic of caveolae. Although eNOS also contains a caveolin binding motif, this is insufficient for correct targeting of eNOS to caveolae. Recent evidence obtained from ventricular myocytes of mice with targeted disruption of the eNOS gene indicates that the lack of functional eNOS interrupts muscarinic cholinergic control of ICA‐L in these cells. eNOS‐/‐mice are hypertensive and develop cardiac hypertrophy as they age, and these animals also exhibit an accelerated degree of vascular remodeling in response to injury. Reconstitution experiments confirm both the essential role of eNOS in coupling m2 AchR signaling to the control of ICA‐L and myocyte automaticity and the importance of eNOS subcellular localization within caveolae in mediating this signal transduction pathway. It appears that translocation into caveolae is essential for signaling. However, this is not the case with all receptors associated with caveolae.
Mitochondrial ATP‐Dependent Potassium Channels: Viable Candidate Effectors of Ischemic Preconditioninga
Authors: LIU YONGGE , SATO TOSHIAKI , SEHARASEYON JEGATHEESAN , SZEWCZYK ADAM , O'ROURKE BRIAN , MARBÁN EDUARDO
Published: February 2006

Abstract: Pharmacological evidence has implicated ATP‐dependent potassium (KATP) channels in the mechanism of ischemic preconditioning; however, the effects of sarcolemmal KATP channels on excitability cannot account for the protection. KATP channels also exist in mitochondrial inner membrane. To test whether such channels play a role in cardioprotection, we simultaneously measured flavoprotein fluorescence, an index of mitochondrial redox state, and sarcolemmal KATP currents in intact rabbit ventricular myocytes. Our results show that diazoxide, a KATP channel opener, induced reversible oxidation of flavoproteins, but did not activate sarcolemmal KATP channels. This effect of diazoxide was blocked by 5‐hydroxydecanoic acid (5‐HD). We further verified that 5‐HD is a selective blocker of the mitochondrial KATP channels. These methods have enabled us to demonstrate that the activity of mitochondrial KATP channels can be regulated by protein kinase C. In a cellular model of simulated ischemia, inclusion of diazoxide decreased the rate of cell death to about half of that in control. Such protection is inhibited by 5‐HD. In conclusion, our results demonstrate that diazoxide targets mitochondrial but not sarcolemmal KATP channels, and imply that mitochondrial KATP channels may mediate pre‐conditioning.
The Molecular Mechanism of Cardiac Hypertrophy and Failure
Authors: YAMAZAKI TSUTOMU , KOMURO ISSEI , SHIOJIMA ICHIRO , YAZAKI YOSHIO
Published: February 2006

Abstract: Mechanical stretch induced by high blood pressure is an initial factor leading to cardiac hypertrophy. In an in vivo study, an angiotensin II (AngII) type 1 receptor antagonist TCV116 reduced left ventricular (LV) weight, LV wall thickness, transverse myocyte diameter, relative amount of V3 myosin heavy chain, and interstitial fibrosis, while treatment with hydralazine did not. In an in vitro study using cultured cardiomyocytes, mechanical stretch activated second messengers such as mitogen‐activated protein (MAP) kinase, followed by increased protein synthesis. Additionally, in the stretch‐conditioned medium AngII and endothelin‐1 concentrations were increased. Furthermore, the Na+/H+ exchanger activated by mechanical stretch modulated the hypertrophic responses of cardiomyocytes. The pathways leading to MAP kinase activation differed between cell types. In cardiac fibroblasts AngII activated MAP kinase via Gβγ subunit of Gi, Src, Shc, Grb2, and Ras, whereas Gq and protein kinase C were critical in cardiomyocytes.