bluuebunny/crossref_metadata_2025 huggingface dataset:
MAGNIFYING ENDOSCOPIC OBSERVATION OF THE UPPER GASTROINTESTINAL TRACT
Authors: Kumagai Youichi , Iida Michio , Yamazaki Shigeru
Published: May 2006

Recent advances in technology enable us to obtain more detailed information during endoscopic procedures. Diagnosis of the pit pattern or microvascular architecture allow the earlier detection of neoplastic lesions in the gastrointestinal tract. These advances have led to the enhanced selection of appropriate treatments. Cancers that are discovered at an early stage can be treated by mucosal resection, whereas advanced cancers are treated with surgery. Recently, some groups have tried to acquire direct in vivo histological images of gastrointestinal mucosa (virtual histology or optical biopsy). Now optical coherence tomography (OCT), confocal laser endoscopy and endo‐cytoscopy systems enable this conception. However, none of these techniques has been proven, although some investigators have been able to use them to enhance cancer detection, and have reported the usefulness of these techniques. The present review assesses the strengths and weaknesses of these technologies, and describes the magnifying observations of the upper gastrointestinal tract using magnifying endoscopy equipment available on the market as well as newly developed endo‐cytoscopy systems. Published and unpublished data for this review were identified by searches of MEDLINE, Register of Cancer Trials: National Cancer Institute (http://cancertrials.nci.nih.gov/) and references from relevant articles. We also contacted researchers. The authors’ own database of references was also used. The search items were as follows: magnifying endoscopy, endo‐cytoscopy system, confocal endoscopy, optical coherence tomography, contact endoscopy, esophageal cancer, Barrett’s esophagus, Barrett’s esophageal cancer, gastric cancer, colon cancer, chromoendoscopy, methylene blue etc.
Multivariate genetic analysis of atopy phenotypes in a selected sample of twins
Authors: Thomsen S. F. , Ulrik C. S. , Kyvik K. O. , Ferreira M. A. R. , Backer V.
Published: May 2006

Background
Atopic traits often co‐occur and this can potentially be caused by common aetiological relationships between traits, i.e. a common genetic or a common environmental background.

Objective
To estimate to what extent the same genetic and environmental factors influence wheeze, rhinitis, airway hyper‐responsiveness (AHR), and positive skin prick test (posSPT) in a sample of adult twins.

Methods
Within a sampling frame of 21 162 twin subjects, 20–49 years of age, from the Danish Twin Registry, a total of 575 subjects (256 intact pairs and 63 single twins), who either themselves and/or their co‐twins reported a history of asthma at a nationwide questionnaire survey, were clinically examined. Symptoms of wheeze and rhinitis were obtained by interview; airway responsiveness and skin test reactivity were measured using standard techniques. Correlations in liability between the different traits were estimated and latent factor models of genetic and environmental effects were fitted to the observed data using maximum likelihood methods.

Results
The various phenotypic correlations between wheeze, rhinitis, AHR and posSPT were all significant and ranged between 0.50 and 0.86. Traits that showed highest genetic correlations were wheeze–rhinitis (ρA=0.95), wheeze–AHR (ρA=0.85) and rhinitis–posSPT (ρA=0.92), whereas lower genetic correlations were observed for rhinitis–AHR (ρA=0.43) and AHR–posSPT (ρA=0.59). Traits with a high degree of environmental sharing were rhinitis–posSPT (ρE=0.92) and wheeze–posSPT (ρE=0.71), whereas a lower environmental correlation was seen for wheeze–rhinitis (ρE=0.25). The estimates were corrected for ascertainment and adjusted for age, sex, inhaled corticosteroids and smoking.

Conclusions
Different atopic conditions share, to a large extent, a common genetic background. In particular, upper and lower respiratory symptoms seem to be different phenotypic expressions of a common set of genes. These results add new insight into the origins of clinical heterogeneity within atopy and should stimulate the search for pleiotropic genes of importance for these conditions.
Antimicrobial Peptide LL‐37 Internalized by Immature Human Dendritic Cells Alters their Phenotype
Authors: Bandholtz L. , Ekman G. Jacobsson , Vilhelmsson M. , Buentke E. , Agerberth B. , Scheynius A. , Gudmundsson G. H.
Published: May 2006

The human cathelicidin LL‐37 has been shown to be involved in the barrier function of the innate immunity, being released from specific cells upon challenge and exerting immunomodulatory effects. We here demonstrate that LL‐37 affects immature dendritic cells, derived from human peripheral blood monocytes (MDDC). LL‐37 is internalized by MDDC with subsequent localization primarily in the cytoplasmic compartment. However, LL‐37 could also be detected in the nuclei of MDDC, suggesting that LL‐37 may be transported into the nucleus. The uptake of LL‐37 is dose, time and energy dependent, indicating that the observed internalization process involves an endocytic pathway. Incubation of immature MDDC with LL‐37 caused phenotypic changes, characterized by an increased expression of the antigen‐presenting molecule HLA‐DR, and the costimulatory molecule CD86. Taken together, these findings suggest that LL‐37 released upon triggering of the innate immunity, may affect cellular adaptive immunity through an interaction with immature dendritic cells.
Analysis of 87 patients with Löfgren’s syndrome and the pattern of seasonality of subacute sarcoidosis
Authors: SIPAHI DEMIRKOK Sevtap , BASARANOGLU Metin , DERVIS Emine , BAL Mert , KARAYEL Tuncer
Published: May 2006

Background and objective:  Sarcoidosis is a multisystem disease of unknown aetiology. The seasonality of sarcoidosis in symptomatic, recently diagnosed patients with Löfgren’s syndrome was evaluated to help better understand the possible causative factor(s) in the pathogenesis of sarcoidosis.

Methods:  Four hundred and ninety‐two consecutive patients with sarcoidosis were investigated. The demographic and clinical features, course of the disease, initial diagnostic methods and both the month and age at initial diagnosis for each patient were analysed. Roger’s test for cyclic variation was used to determine the significance of any seasonal variation of incidence.

Results:  Löfgren’s syndrome was diagnosed in 87 patients (18%). The diagnosis of sarcoidosis was delayed in 45% of subjects (mean: 11.2 weeks). The distribution of cumulative monthly presentations peaked in May (spring) and was the lowest in January (winter) and November (autumn) (P < 0.001). The seasonal pattern was also influenced by age and gender (P < 0.05). At the onset, arthralgia was present in 46%, cough or dyspnoea in 37%, constitutional symptoms in 32% and skin lesions in 30% of the patients.

Conclusions:  In this study, there were differences in the amplitude of the seasonal variation by age and by gender. Well‐designed prospective studies are required to better understand the importance of the findings we respect to the pathogenesis of the disease.
A phyletic perspective on the allometry of plant biomass‐partitioning patterns and functionally equivalent organ‐categories
Authors: Niklas Karl J.
Published: May 2006

Biomass‐partitioning patterns influence the functioning of aquatic and terrestrial vegetation at all levels, ranging from individual growth and reproduction to the flow of mass and energy through entire communities. For this reason, leaf, stem and root dry biomass‐partitioning patterns across taxonomically and ecologically diverse seed plants (spermatophytes) have been intensively investigated, both empirically and theoretically. By contrast, phyletically disparate plants (e.g. green and brown algal macrophytes, mosses and pteridophytes) have not been examined to determine whether the partitioning of their body parts into ‘leaf’, ‘stem’ and ‘root’ analogs accords with that of spermatophytes. In this review, the biomass‐partitioning patterns of siphonous and brown algal macrophytes, mosses and pteridophytes were compared allometrically with those of spermatophytes and were shown to be largely in statistical accordance (thus lending support to the hypothesis that a single scaling relationship exists across eukaryotic photoautotrophs). This concordance is argued to support the hypothesis of functional equivalence across analogous, but developmentally different, body parts, a feature that permits the use of simpler biological model systems with which to derive analytical explanations for the biomass‐partitioning patterns reported for more complex seed plants.

ContentsSummary27I.Introduction28II.Statistical considerations30III.Phyletic considerations and the null hypothesis31IV.Observable biomass‐partitioning patterns32V.Two intraspecific digressions34VI.The functional equivalence hypothesis35VII.Plato's cave38VIII.Conclusions38Acknowledgements39References39
Mechanical Evaluation of Pin and Tension‐Band Wire Factors in an Olecranon Osteotomy Model
Authors: NEAT BENJAMIN C. , KOWALESKI MICHAEL P. , LITSKY ALAN S. , BOUDRIEAU RANDY J.
Published: May 2006

Objective— To evaluate the effect of altering pin and wire diameter, wire position and configuration, and osteotomy angle on applied load and absorbed strain energy in a pin and tension‐band wire (PTBW) fixation model.

Study Design— In vitro mechanical study.

Sample Population— Delrin® models (n=96).

Methods— PTBW was applied to Delrin® olecranon osteotomy models. A control configuration was defined and then altered, 1 variable (wire diameter, pin diameter, wire‐hole position, wire configuration, osteotomy angle) at a time, to create 11 test configurations. Tensile force was applied and displacement at the caudal aspect of the osteotomy was measured. Fixation strength, in terms of tensile load and strain energy, was compared between control and each test configuration at 4 osteotomy displacements.

Results— Models with larger wire, pins, or combined figure‐of‐eight/lateral wires were stronger than control, whereas those with smaller wire, pins, or a solitary lateral wire were weaker. The superior strength of the larger wire was apparent for all assessed osteotomy displacement.

Conclusions— PTBW fixation strength increases as implant diameter is increased, with wire diameter having greatest effect. Lateral wire configuration is weaker than figure‐of‐eight, but can be added to figure‐of‐eight configuration to increase strength. Wire‐hole position and osteotomy angle have little effect on PTBW strength.

Clinical Relevance— Wire diameter is the key determinant of PTBW strength, whereas pin diameter is somewhat less critical. Wire passage through an additional hole proximally provides equivalent strength and may avoid soft‐tissue entrapment and subsequent loosening.
Understanding Risk Management
Authors: Döderlein Jan M.
Published: May 2006

Discussions of technological risks and their management by corporations and society are ubiquitous and often acrimonious. Equally ubiquitous are several important misconceptions of key risk questions. This paper (i) argues that serious epistemological confusion pervades much of the scientific basis for risk assessment, especially confusion among objective, subjective, and perceived risk, and between facts and ethical values; and (ii) asserts that this confusion combines with psychological aspects of risk perception to produce a confused risk debate, a societal management of risks often based on diffuse or contradictory objectives, and consequently mismanagement of resource allocation to risk reduction.
How Close Is Close Enough: Public Perceptions of the Risks of Industrial Facilities
Authors: Lindell Michael K. , Earle Timothy C.
Published: May 2006

Public opinion poll data have consistently shown that the proportion of respondents who are willing to have a nuclear power plant in their own community is smaller than the proportion who agree that more nuclear plants should be built in this country. Respondents’ judgments of the minimum safe distance from each of eight hazardous facilities confirmed that this finding results from perceived risk gradients that differ by facility (e.g., nuclear vs. natural gas power plants) and social group (e.g., chemical engineers vs. environmentalists) but are relatively stable over time. Ratings of the facilities on thirteen perceived risk dimensions were used to determine whether any of the dimensions could explain the distance data. Because the rank order of the facilities with respect to acceptable distance was very similar to the rank order on a number of the perceived risk dimensions, it is difficult to determine which of the latter is the critical determinant of acceptable distance if, indeed, there is only one. There were, however, a number of reversals of rank order that indicate that the respondents had a differentiated view of technological risk. Finally, data from this and other studies were interpreted as suggesting that perceived lack of any other form of personal control over risk exposure may be an important factor in stimulating public opposition to the siting of hazardous facilities.
The ultraluminous X-ray source in M82: an intermediate-mass black hole with a giant companion
Authors: Patruno A. , Portegies Zwart S. , Dewi J. , Hopman C.
Published: May 2006

The starburst galaxy M82, at a distance of 12 million light years, is the host of an unusually bright 2.4-16 × 1040 erg s−1 X-ray point source, which is best explained by an accreting black hole 102 to 104 times more massive than the Sun. Though the strongest candidate for a so-called intermediate-mass black hole, the only support stems from the observed luminosity and the 0.05-0.1 Hz quasi-periodicity in its signal. Interestingly, the 7-12 Myr old star cluster MGG-11 which has been associated with the X-ray source is sufficiently dense that an intermediate mass black hole could have been produced in the cluster core via collision runaway. The recently discovered 62.0 ± 2.5 d periodicity in the X-ray source X-1 further supports the hypothesis that this source is powered by a black hole several hundred times more massive than the Sun. We perform detailed binary evolution simulations with an accreting compact object of 10-5000 M⊙ and find that the X-ray luminosity, the age of the cluster, the observed quasi-periodic oscillations and the now observed orbital period are explained best by a black hole of 200-5000 M⊙ that accretes material from a 22-25 M⊙ giant companion in a state of Roche-lobe contact. Interestingly, such a companion star is consistent with the expectation based on the tidal capture in a young and dense star cluster such as MGG-11, making the picture self-consistent.
SENSORY AND RHEOLOGICAL CHARACTERIZATION OF LOW‐FAT STIRRED YOGURT
Authors: JANHØJ THOMAS , PETERSEN CHARLOTTE BLANGSTED , FRØST MICHAEL BOM , IPSEN RICHARD
Published: May 2006

With the specific objective of investigating the sensory concept of creaminess, as well as other sensory attributes obtained from descriptive analysis, a set of 25 samples of stirred low‐fat yogurt were submitted to rheological (shear and imperfect squeeze flow viscometry, dynamic oscillation and Posthumus funnel) and sensory testing. Fat levels ranged from 0.3 to 3.5% and protein from 3.4 to 6.0%, and four different protein sources were employed, one being skimmed milk powder, the remaining three were milk protein preparations, one of which contained partially microparticulated whey protein (MPP). Based on averaged data from the sensory panel (n = 12), creaminess could be modeled by two other sensory descriptors, oral viscosity and smoothness (R2 = 0.78), but was poorly modeled by the entire set of rheological data. The MPP‐containing blend did best in terms of matching the creaminess scores of a control yogurt containing 3.5% fat (no additional protein added).
Pursuit Speed Compensation in Cortical Area MSTd
Authors: Shenoy Krishna V. , Crowell James A. , Andersen Richard A.
Published: May 2006

When we move forward the visual images on our retinas expand. Humans rely on the focus, or center, of this expansion to estimate their direction of self-motion or heading and, as long as the eyes are still, the retinal focus corresponds to the heading. However, smooth pursuit eye movements add visual motion to the expanding retinal image and displace the focus of expansion. In spite of this, humans accurately judge their heading during pursuit eye movements even though the retinal focus no longer corresponds to the heading. Recent studies in macaque suggest that correction for pursuit may occur in the dorsal aspect of the medial superior temporal area (MSTd); neurons in this area are tuned to the retinal position of the focus and they modify their tuning to partially compensate for the focus shift caused by pursuit. However, the question remains whether these neurons shift focus tuning more at faster pursuit speeds, to compensate for the larger focus shifts created by faster pursuit. To investigate this question, we recorded from 40 MSTd neurons while monkeys made pursuit eye movements at a range of speeds across simulated self- or object motion displays. We found that most MSTd neurons modify their focus tuning more at faster pursuit speeds, consistent with the idea that they encode heading and other motion parameters regardless of pursuit speed. Across the population, the median rate of compensation increase with pursuit speed was 51% as great as required for perfect compensation. We recorded from the same neurons in a simulated pursuit condition, in which gaze was fixed but the entire display counter-rotated to produce the same retinal image as during real pursuit. This condition yielded the result that retinal cues contribute to pursuit compensation; the rate of compensation increase was 30% of that required for accurate encoding of heading. The difference between these two conditions was significant ( P < 0.05), indicating that extraretinal cues also contribute significantly. We found a systematic antialignment between preferred pursuit and preferred visual motion directions. Neurons may use this antialignment to combine retinal and extraretinal compensatory cues. These results indicate that many MSTd neurons compensate for pursuit velocity, pursuit direction as previously reported and pursuit speed, and further implicate MSTd as a critical stage in the computation of egomotion.
Chronic NMDA Receptor Blockade From Birth Delays the Maturation of NMDA Currents, but Does Not Affect AMPA/Kainate Currents
Authors: Colonnese Matthew T. , Shi Jian , Constantine-Paton Martha
Published: May 2006

The activity of the N-methyl-d-aspartate receptor (NR) regulates the composition of excitatory synapses and mediates multiple forms of synaptic and structural plasticity. In the superficial superior colliculus (sSC) of the rat, NR activity is essential for the full refinement of retinotopy during development. We have examined the NR's role in synaptic development by chronically treating the sSC from birth with the competitive antagonist (±)-2-amino-5-phosphonopentanoic acid (AP5) released by the slow-release polymer Elvax. Whole-cell voltage-clamp recordings were used to characterize excitatory postsynaptic potentials (EPSCs) in slices from postnatal day (P)12–20 sSC. Chronic NR blockade reduced the ratio of AMPA/kainate receptor (AMPAR) to NR peak current amplitudes of both spontaneous (s)EPSCs and evoked EPSCs. Spontaneous NR current amplitude was increased following treatment, while spontaneous AMPAR currents were identical to those of controls, indicating that the ratio change was due to an increased NR current. Comparison of sEPSC frequency, AMPAR current rectification, and quantitative Western blots indicated that the characteristics of AMPARs at the synapse are normal following AP5 treatment. In the sSC, NR currents show a rapid decrease in decay time on P11 and previous studies in slices indicate this change results from a NR-mediated activation of the phosphatase calcineurin. Consistent with this in vitro finding, the down-regulation failed to occur in sSC chronically treated with AP5 in vivo. Together the present data show that NR function is necessary for subsequent NR current regulation in vivo, but it is not essential for the developmental expression of normal AMPAR currents.
Development of Echolocation Calls in the Mustached Bat,Pteronotus parnellii
Authors: Vater M. , Kössl M. , Foeller E. , Coro F. , Mora E. , Russell I. J.
Published: May 2006

Adult mustached bats employ Doppler-sensitive sonar to hunt fluttering prey insects in acoustically cluttered habitats. The echolocation call consists of 4–5 harmonics, each composed of a long constant frequency (CF) component flanked by brief frequency modulations (FM). The 2nd harmonic CF component (CF2) at 61 kHz is the most intense, and analyzed by an exceptionally sharply tuned auditory system. The maturation of echolocation calls and the development of Doppler-shift compensation was studied in Cuba where large maternity colonies are found in hot caves. In the 1st postnatal week, infant bats did not echolocate spontaneously but could be induced to vocalize CF-FM signals by passive body motion. The CF2frequency emitted by the smallest specimens was at 48 kHz (i.e., 0.4 octaves lower than the adult signal). CF-FM signals were spontaneously produced in the 2nd postnatal week at a CF2frequency of 52 kHz. The CF2frequencies of induced and spontaneous calls shifted upward to reach a value of 60.5 kHz in the 5th postnatal week. Standard deviations of CF2frequency were large (up to ±1.5 kHz) in the youngest bats and dropped to values of ±250 Hz at the end of the 3rd postnatal week. Some individuals in the 4th and 5th postnatal weeks emitted with adultlike frequency precision of about ±100 Hz. In the youngest bats, the 1st harmonic CF component (CF1) was up to 22 dB stronger than CF2. Adultlike relative levels of CF1(–28 dB relative to CF2) were reached in the 5th postnatal week. In spontaneously emitted CF-FM calls, the duration of the CF2component gradually increased with age from 5 ms to maximum values of 18 ms. Durations of the CF2component in induced calls averaged 7 ± 2.6 ms in the 1st postnatal week and 8.2 ± 1.5 ms in the 5th postnatal week. There were no age-related changes in duration of the terminal FM sweep (3 ± 0.4 ms) in both induced and spontaneous calls. The magnitude of the terminal FM sweep in spontaneous calls was not correlated with age (mean 13.5 ± 2 kHz). Values for induced calls slightly increased with age from 11 ± 2 to 13 ± 2 kHz. The emission rate of induced CF-FM signals increased with age from values of 2.5 ± 2 to 17 ± 5 pulses/s. Values for spontaneously emitted calls were 4.4 ± 3 and 9 ± 4.5 pulses/s, respectively. Doppler-shift compensation, as tested in the pendulum task, emerged during the 4th postnatal week in young bats that were capable of very brief active flights, but before the time of active foraging outside the cave.
Cerebellar Control of Constrained and Unconstrained Movements. II. EMG and Nuclear Activity
Authors: Goodkin H. P. , Thach W. T.
Published: May 2006

The aim of this study was to see in monkeys if neurons in dentate and lateral interposed deep cerebellar nuclei are preferentially active in relation to certain movements relative to others. Simple and compound digit movements were trained with digits, hand, and elbow constrained in a cast. The constrained simple movement was flexion of Thumb or Index; the constrained compound movement, flexion of Thumb+Index. An unconstrained compound movement consisted of a reach to, pinch of, and retrieval of a small food reward (Reach+Pinch). Electromyographic (EMG) recording showed that many muscles in the upper extremity, shoulder girdle, and trunk were active in all movements. EMG/muscle stimulation during the constrained digit movements showed that the digit prime movers were active during, sufficient for, and necessary for performance of these digit tasks. By contrast, EMG/muscle stimulation showed that the proximal muscles (though co-active during the tasks) were neither sufficient nor necessary for performance of the digit tasks. A fraction of those neurons that were active during both the constrained and the unconstrained movements fired at a higher frequency during the unconstrained task. Some neurons were active during Reach+Pinch only; a few others were active during one or more of Thumb, Index, Thumb+Index only. There was no distinct preferential discharge relationship to the compound Thumb+Index as compared with the simple Thumb or Index. These correlational data are consistent with an interpretation that the cerebellar discharge influenced all of these movements—simple and compound, constrained, and unconstrained—no one type seemingly more than any other.
Acoustic Startle Evokes Bilaterally Synchronous Oscillatory EMG Activity in the Healthy Human
Authors: Grosse Pascal , Brown Peter
Published: May 2006

Despite animal evidence that the reticulospinal system is of major importance to movement, this motor pathway has remained relatively inaccessible to experimentation in the human. Consequently, little is known about its function in health and disease. Here, we use the acoustic startle response to demonstrate that one type of reticulospinal activity in the human is associated with a characteristic pattern of bilateral synchronization between motor units. Surface electromyography (EMG) was recorded from upper limb muscles in 15 healthy subjects during the reflex startle to unexpected acoustic stimulation, voluntary movements mimicking the startle and during sustained voluntary tonic contraction. Frequency analysis demonstrated autospectral peaks at ∼14 Hz in deltoid and biceps muscles only during the startle reflex. Similarly, coherence spectra of the EMG recorded between homologous proximal upper limb muscles demonstrated a peak centered ∼12–16 Hz during reflex startles. Coherence in the 10- to 20-Hz band was significantly greater in the startle reflex than during voluntary sham startles or voluntary tonic contraction for deltoid, but not first dorsal interosseous, muscles. The coherence at 10–20 Hz between EMGs from homologous muscles represents a potential surrogate measure of reticulospinal activity that may be useful in determining the contribution of the reticulospinal system to different types of movement in health and disease.
Multiple Presynaptic and Postsynaptic Sites of Inhibitory Modulation by Myomodulin at ARC Neuromuscular Junctions ofAplysia
Authors: Orekhova Irina V. , Alexeeva Vera , Church Paul J. , Weiss Klaudiusz R. , Brezina Vladimir
Published: May 2006

The functional activity of even simple cellular ensembles is often controlled by surprisingly complex networks of neuromodulators. One such network has been extensively studied in the accessory radula closer (ARC) neuromuscular system of Aplysia. The ARC muscle is innervated by two motor neurons, B15 and B16, which release modulatory peptide cotransmitters to shape ACh-mediated contractions of the muscle. Previous analysis has shown that key to the combinatorial ability of B15 and B16 to control multiple parameters of the contraction is an asymmetry in their peptide modulatory actions. B16, but not B15, releases myomodulin, which, among other actions, inhibits the contraction. Work in single ARC muscle fibers has identified a distinctive myomodulin-activated K current as a candidate postsynaptic mechanism of the inhibition. However, definitive evidence for this mechanism has been lacking. Here, working with the single fibers and then motor neuron-elicited excitatory junction potentials (EJPs) and contractions of the intact ARC muscle, we have confirmed two central predictions of the K-current hypothesis: the myomodulin inhibition of contraction is associated with a correspondingly large inhibition of the underlying depolarization, and the inhibition of both contraction and depolarization is blocked by 4-aminopyridine (4-AP), a potent and selective blocker of the myomodulin-activated K current. However, in the intact muscle, the experiments revealed a second, 4-AP-resistant component of myomodulin inhibition of both B15- and B16-elicited EJPs. This component resembles, and mutually occludes with, inhibition of the EJPs by another peptide modulator released from both B15 and B16, buccalin, which acts by a presynaptic mechanism, inhibition of ACh release from the motor neuron terminals. Direct measurements of peptide release showed that myomodulin also inhibits buccalin release from B15 terminals. At the level of contractions, nevertheless, the postsynaptic K-current mechanism is responsible for much of the myomodulin inhibition of peak contraction amplitude. The presynaptic mechanism, which is most evident during the initial build-up of the EJP waveform, underlies instead an increase of contraction latency.
Coordinated Turn-and-Reach Movements. II. Planning in an External Frame of Reference
Authors: Pigeon Pascale , Bortolami Simone B. , DiZio Paul , Lackner James R.
Published: May 2006

The preceding study demonstrated that normal subjects compensate for the additional interaction torques generated when a reaching movement is made during voluntary trunk rotation. The present paper assesses the influence of trunk rotation on finger trajectories and on interjoint coordination and determines whether simultaneous turn-and-reach movements are most simply described relative to a trunk-based or an external reference frame. Subjects reached to targets requiring different extents of arm joint and trunk rotation at a natural pace and quickly in normal lighting and in total darkness. We first examined whether the larger interaction torques generated during rapid turn-and-reach movements perturb finger trajectories and interjoint coordination and whether visual feedback plays a role in compensating for these torques. These issues were addressed using generalized Procrustes analysis (GPA), which attempts to overlap a group of configurations (e.g., joint trajectories) through translations and rotations in multi-dimensional space. We first used GPA to identify the mean intrinsic patterns of finger and joint trajectories (i.e., their average shape irrespective of location and orientation variability in the external and joint workspaces) from turn-and-reach movements performed in each experimental condition and then calculated their curvatures. We then quantified the discrepancy between each finger or joint trajectory and the intrinsic pattern both after GPA was applied individually to trajectories from a pair of experimental conditions and after GPA was applied to the same trajectories pooled together. For several subjects, joint trajectories but not finger trajectories were more curved in fast than slow movements. The curvature of both joint and finger trajectories of turn-and-reach movements was relatively unaffected by the vision conditions. Pooling across speed conditions significantly increased the discrepancy between joint but not finger trajectories for most subjects, indicating that subjects used different patterns of interjoint coordination in slow and fast movements while nevertheless preserving the shape of their finger trajectory. Higher movement speeds did not disrupt the arm joint rotations despite the larger interaction torques generated. Rather, subjects used the redundant degrees of freedom of the arm/trunk system to achieve similar finger trajectories with differing joint configurations. We examined finger movement patterns and velocity profiles to determine the frame of reference in which turn-and-reach movements could be most simply described. Finger trajectories of turn-and-reach movements had much larger curvatures and their velocity profiles were less smooth and less bell-like in trunk-based coordinates than in external coordinates. Taken together, these results support the conclusion that turn-and-reach movements are controlled in an external frame of reference.
Perception and Reproduction of Force Direction in the Horizontal Plane
Authors: Toffin D. , McIntyre J. , Droulez J. , Kemeny A. , Berthoz A.
Published: May 2006

In this study, we evaluated the capacity of human beings to perceive and reproduce forces applied to the hand. We tested for perceptive distortions and/or privileged directions in the performance of these two tasks. Subjects resisted a reference force applied by a joystick in a given direction, with instructions to keep the hand at a constant position. In a perception task, subjects subsequently resisted a second such force, the direction of which they could adjust with a potentiometer; the task was to reorient the second force to be in the same perceived direction as the reference. In a reproduction task, subjects were instructed to push against the now elastically constrained joystick with the same force that was required to resist the initially applied reference force. Twenty-four reference force directions in the horizontal plane were tested twice each. We observed systematic distortions in the reproduction of force direction that were not present in the perception task. We further observed that the distortions could be predicted by anisotropy of limb stiffness and could be affected by manipulating the mechanical impedance of the hand-joystick interaction. We conclude that human subjects specify and store forces to be applied by the hand not in terms of a perceived force vector, but rather in terms of the motor activity required to resist or produce the force—i.e., subjects possess a multi-dimensional “sense of effort.”
Dissociating Cortical Regions Activated by Semantic and Phonological Tasks: A fMRI Study in Blind and Sighted People
Authors: Burton H. , Diamond J. B. , McDermott K. B.
Published: May 2006

Previous neuroimaging studies of language processing in blind individuals described cortical activation of primary (V1) and higher tier visual areas, irrespective of the age of blindness onset. Specifically, participants were given nouns and asked to generate an associated verb. These results confirmed the presence of adaptations in the visual cortex of blind people and suggested that these responses represented linguistic operations. The present functional magnetic resonance imaging study attempted to further characterize these responses as being preferential for semantic or phonological processing. Three groups of participants (sighted, earlyonset, and late-onset blind) heard lists of related words and attended to either a common meaning (semantic task) or common rhyme (phonological task) that linked the words. In all three groups, the semantic task elicited stronger activity in the left anterior inferior frontal gyrus and the phonological task evoked stronger activity bilaterally in the inferior parietal cortex and posterior aspects of the left inferior frontal gyrus. Only blind individuals showed activity in occipital, temporal, and parietal components of visual cortex. The spatial extent of visual cortex activity was greatest in early blind, who exhibited activation in all ventral and dorsal visual cortex subdivisions (V1 through MT) for both tasks. Preferential activation appeared for the semantic task. Late blind individuals exhibited responses in ventral and dorsal V1, ventral V2, VP and V8, but only for the semantic task. Our findings support prior evidence of visual cortex activity in blind people engaged in auditory language processing and suggest that this activity may be related to semantic processing.
Computational Analysis of Subthalamic Nucleus and Lenticular Fasciculus Activation During Therapeutic Deep Brain Stimulation
Authors: Miocinovic Svjetlana , Parent Martin , Butson Christopher R. , Hahn Philip J. , Russo Gary S. , Vitek Jerrold L. , McIntyre Cameron C.
Published: May 2006

The subthalamic nucleus (STN) is the most common target for the treatment of Parkinson’s disease (PD) with deep brain stimulation (DBS). DBS of the globus pallidus internus (GPi) is also effective in the treatment of PD. The output fibers of the GPi that form the lenticular fasciculus pass in close proximity to STN DBS electrodes. In turn, both STN projection neurons and GPi fibers of passage represent possible therapeutic targets of DBS in the STN region. We built a comprehensive computational model of STN DBS in parkinsonian macaques to study the effects of stimulation in a controlled environment. The model consisted of three fundamental components: 1) a three-dimensional (3D) anatomical model of the macaque basal ganglia, 2) a finite element model of the DBS electrode and electric field transmitted to the tissue medium, and 3) multicompartment biophysical models of STN projection neurons, GPi fibers of passage, and internal capsule fibers of passage. Populations of neurons were positioned within the 3D anatomical model. Neurons were stimulated with electrode positions and stimulation parameters defined as clinically effective in two parkinsonian monkeys. The model predicted axonal activation of STN neurons and GPi fibers during STN DBS. Model predictions regarding the degree of GPi fiber activation matched well with experimental recordings in both monkeys. Only axonal activation of the STN neurons showed a statistically significant increase in both monkeys when comparing clinically effective and ineffective stimulation. Nonetheless, both neural targets may play important roles in the therapeutic mechanisms of STN DBS.
Blockade of Cyclic AMP-Dependent Protein Kinase Does Not Prevent the Reverse Ocular Dominance Shift in Kitten Visual Cortex
Authors: Shimegi Satoshi , Fischer Quentin S. , Yang Yupeng , Sato Hiromichi , Daw Nigel W.
Published: May 2006

Monocular deprivation (MD) during the critical period for the development of visual cortex causes a loss of binocular response of neurons and a shift to the open eye, a normal ocular dominance (OD) shift. However, when MD is combined with chronic inactivation of the visual cortex by muscimol, the OD distribution of the neurons shifts to the deprived eye (reverse OD shift). We have previously shown that the normal OD shift is abolished by chronic infusion of the protein kinase A (PKA) inhibitor, 8-chloroadenosine-3′, 5′-cyclic monophosphorothioate, Rpisomer (Rp-8-Cl-cAMPS), into kitten visual cortex. In this study, we investigated the effect of this inhibitor on the reverse OD shift. Combination of MD and muscimol infusion into the visual cortex of 6-wk-old kittens caused a reverse OD shift that was comparable to that seen in previous studies. However, a reverse OD shift was also seen with concurrent infusion of the PKA inhibitor with muscimol. The strongest OD shift was observed in layer IV regardless of the presence or absence of the PKA inhibitor. This suggests that the dissociation of pre- and postsynaptic activities, which occurs mainly at thalamocortical synapses, induces the reverse OD shift and that inhibition of PKA does not prevent it. Presumably, an inhibition of PKA has no effect in silent cortex. We conclude that 1) an activation of PKA is not required for the induction of the reverse OD shift, and 2) the intracellular signaling mechanism underlying MD-induced OD plasticity differs between normal and reverse OD shifts.
Passive Transport Disrupts Directional Path Integration by Rat Head Direction Cells
Authors: Stackman Robert W. , Golob Edward J. , Bassett Joshua P. , Taube Jeffrey S.
Published: May 2006

A subset of neurons in the rat limbic system encodes head direction (HD) by selectively discharging when the rat points its head in a preferred direction in the horizontal plane. The preferred firing direction is sensitive to the location of landmark cues, as well as idiothetic or self-motion cues (i.e., vestibular, motor efference copy, proprioception, and optic flow). Previous studies have shown that the preferred firing direction remains relatively stable (average shift ± 18°) after the rat walks from a familiar environment into a novel one, suggesting that without familiar landmarks, the preferred firing direction can be maintained using idiothetic cues, a process called directional path integration. This study repeated this experiment and manipulated the idiothetic cues available to the rat as it moved between the familiar and novel environment. Motor efference copy/proprioceptive cues were disrupted by passively transporting the animal between the familiar and novel environment. Darkening the room as the animal moved to the novel environment eliminated optic flow cues. HD cell preferred firing directions shifted in the novel environment by an average of 30° after locomotion from the familiar environment with the room lights off; by an average of 70° after passive transport from the familiar environment with the room lights on; and by an average of 67° after passive transport with the room lights off. These findings are consistent with the view that motor efference copy/proprioception cues are important for maintaining the preferred firing direction of HD cells under conditions requiring path integration.
Dynamical Organization of Directional Tuning in the Primate Premotor and Primary Motor Cortex
Authors: Ben-Shaul Yoram , Stark Eran , Asher Itay , Drori Rotem , Nadasdy Zoltan , Abeles Moshe
Published: May 2006

Although previous studies have shown that activity of neurons in the motor cortex is related to various movement parameters, including the direction of movement, the spatial pattern by which these parameters are represented is still unresolved. The current work was designed to study the pattern of representation of the preferred direction (PD) of hand movement over the cortical surface. By studying pairwise PD differences, and by applying a novel implementation of the circular variance during preparation and movement periods in the context of a center-out task, we demonstrate a nonrandom distribution of PDs over the premotor and motor cortical surface of two monkeys. Our analysis shows that, whereas PDs of units recorded by nonadjacent electrodes are not more similar than expected by chance, PDs of units recorded by adjacent electrodes are. PDs of units recorded by a single electrode display the greatest similarity. Comparison of PD distributions during preparation and movement reveals that PDs of nearby units tend to be more similar during the preparation period. However, even for pairs of units recorded by a single electrode, the mean PD difference is typically large (45° and 75° during preparation and movement, respectively), so that a strictly modular representation of hand movement direction over the cortical surface is not supported by our data.
EEG Slow (∼1 Hz) Waves Are Associated With Nonstationarity of Thalamo-Cortical Sensory Processing in the Sleeping Human
Authors: Massimini Marcello , Rosanova Mario , Mariotti Maurizio
Published: May 2006

Intracellular studies reveal that, during slow wave sleep (SWS), the entire cortical network can swing rhythmically between extremely different microstates, ranging from wakefulness-like network activation to functional disconnection in the space of a few hundred milliseconds. This alternation of states also involves the thalamic neurons and is reflected in the EEG by a slow (<1 Hz) oscillation. These rhythmic changes, occurring in the thalamo-cortical circuits during SWS, may have relevant, phasic effects on the transmission and processing of sensory information. However, brain reactivity to sensory stimuli, during SWS, has traditionally been studied by means of sequential averaging, a procedure that necessarily masks any short-term fluctuation of responsiveness. The aim of this study was to provide a dynamic evaluation of brain reactivity to sensory stimuli in naturally sleeping humans. To this aim, single-trial somatosensory evoked potentials (SEPs) were grouped and averaged as a function of the phase of the ongoing sleep slow (<1 Hz) oscillation. This procedure revealed a dynamic profile of responsiveness, which was conditioned by the phase of the spontaneous sleep EEG. Overall, the amplitude of the evoked potential changed sistematically, increasing and approaching wakefulness levels along the negative slope of the EEG oscillation and decaying below SWS average levels along the positive drift. These marked and fast changes of stimulus-correlated electrical activity involved both short (N20) and long latency (P60 and P100) components of SEPs. In addition, the observed short-term response variability appeared to be centrally generated and specifically related to the evolution of the spontaneous oscillatory pattern. The present findings demonstrate that thalamo-cortical processing of sensory information is not stationary in the very short period (approximately 500 ms) during natural SWS.
Selective Effects of Light Exposure on Distribution of Motility in the Chick Embryo at E18
Authors: Bradley Nina S. , Jahng Dongwon Y.
Published: May 2006

It is well established that orderly patterns of motor neuron activity, muscle recruitment, and limb movement are generated in chicks during motility by embryonic day (E)9, the midpoint in embryonic development. However, our recent work suggests that some attributes of motility, such as the rhythm of repetitive limb movements and distribution of activity, become less orderly after E9. In this study, we extend these observations by performing continuous force recordings over a 24-h period in ovo at E18 with augmented sampling of synchronized video and electromyogram (EMG) recordings. We report the distribution of three repetitive behaviors, rapid limb movement, respiratory-like movement, and beak clapping, identified in force recordings, and the general distribution of motility. We also test a model recently proposed to account for age-related changes in motility parameters. In the model, we proposed that circadian networks contribute to the age-related changes in distribution of motility. As a first test of this hypothesis, we examine whether light exposure contributes to the variable distribution of motility by comparing motility parameters at E18 for embryos incubated and tested under either a 12-h light/dark cycle or continuous light. Results suggest that exposure to light increases the total amount of activity and hastens the onset of extended respiratory-like movement sequences but does not impact expression of repetitive limb movement or beak clapping at E18. The possible influence of circadian mechanisms on embryonic behavior and insensitivity of repetitive limb movements to light exposure are discussed.
Interaction Between Gaze and Pointing Toward Remembered Visual Targets
Authors: Admiraal M. A. , Keijsers N.L.W. , Gielen C.C.A.M.
Published: May 2006

We examined the role of gaze in a task where subjects had to reproduce the position of a remembered visual target with the tip of the index finger, referred to as pointing. Subjects were tested in 3 visual feedback conditions: complete darkness (dark), complete darkness with visual feedback of the finger position (finger), and with vision of a well-defined environment and feedback of the finger position (frame). Pointing accuracy increases with feedback about the finger or visual environment. In the finger and frame conditions, the 95% confidence regions of the variable errors have an ellipsoidal distribution with the main axis oriented toward the subjects' head. During the 1-s period when the target is visible, gaze is almost on target. However, gaze drifts away from the target relative to the subject in the delay period after target disappearance. In the finger and frame conditions, gaze returns toward the remembered target during pointing. In all 3 feedback conditions, the correlations between the variable errors of gaze and pointing position increase during the delay period, reaching highly significant values at the time of pointing. Our results demonstrate that gaze affects the accuracy of pointing. We conclude that the covariance between gaze and pointing position reflects a common drive for gaze and arm movements and an effect of gaze on pointing accuracy at the time of pointing. Previous studies interpreted the orientation of variable errors as indicative for a frame of reference used for pointing. Our results suggest that the orientation of the error ellipses toward the head is at least partly the result of gaze drift in the delay period.