bluuebunny/crossref_metadata_2025 huggingface dataset:
The Nature of V1 Neural Responses to 2D Moving Patterns Depends on Receptive-Field Structure in the Marmoset Monkey
Authors: Tinsley Chris J. , Webb Ben S. , Barraclough Nick E. , Vincent Chris J. , Parker Amanda , Derrington Andrew M.
Published: May 2006

A plaid pattern is formed when two sinusoidal gratings of different orientations are added together. Previous work has shown that V1 neurons selectively encode the direction and orientation of the component gratings in a moving plaid but not the direction of the plaid itself ( Movshon et al. 1985 ). We recorded the responses of 49 direction-selective neurons to moving gratings and plaid patterns in area V1 of the anesthetized marmoset monkey ( Callithrix jacchus). The responses of V1 neurons to rectangular patches of varying lengths and widths containing gratings of optimal spatial frequency were used to measure size and aspect ratio of the receptive-field subunits. We measured responses to plaid patterns moving in different directions and graded the magnitude of the response to the direction of motion of the plaid and the response to the direction of motion of the component gratings. We found significant correlations between receptive-field structure and the type and strength of its response to moving plaid patterns. The strength of pattern and component responses was significantly correlated with the interrelated properties of direction tuning width (Spearman's r = 0.82, P < 0.001), and receptive-field subunit aspect ratio (Spearman's r = –0.79, P < 0.001). Neurons with broad direction tuning and short, wide receptive-field subunits gave their greatest response when the plaid moved in their preferred direction. Conversely, neurons with narrow direction tuning and long, narrow receptive-field subunits gave their greatest responses when the plaid moved in a direction such that one of its components moved in the preferred direction.
Neuronal Aggregate Formation Underlies Spatiotemporal Dynamics of Nonsynaptic Seizure Initiation
Authors: Bikson Marom , Fox John E. , Jefferys John G. R.
Published: May 2006

High-frequency activity often precedes seizure onset. We found that electrographic seizures, induced in vitro using the low-Ca2+ model, start with high-frequency (>150 Hz) activity that then decreases in frequency while increasing in amplitude. Multichannel and unit recordings showed that the mechanism of this transition was the progressive formation of larger neuronal aggregates. Thus the apparenthigh-frequency activity, at seizure onset, can reflect the simultaneous recording of several slower firing aggregates. Aggregate formation rate can be accelerated by reducing osmolarity. Because synaptic transmission is blocked when extracellular Ca2+ is reduced, nonsynaptic mechanisms (gap junctions, field effects) must be sufficient for aggregate formation and recruitment.
G Protein Signaling in a Neuronal Network is Necessary for Rhythmic Motor Pattern Production
Authors: Clemens Stefan , Katz Paul S.
Published: May 2006

G protein-coupled receptors are widely recognized as playing important roles in mediating the actions of extrinsic neuromodulatory inputs to motor networks. However, the potential for their direct involvement in rhythmic motor pattern generation has received considerably less attention. Results from this study indicate that G protein signaling appears to be integral to the operation of the central pattern generator (CPG) underlying the escape swim of the mollusk Tritonia diomedea. Blocking G protein signaling in a single CPG neuron, cerebral neuron C2, with intracellular iontophoresis of the guanine nucleotide analogue guanosine 5′- O-(2-thiodiphosphate) (GDP-β-S), prevented the production of the swim motor program. Moreover, tonic activation of G protein signaling in this neuron by iontophoresis of the GTP analogues guanosine 5′- O-(3-thiotriphosphate) (GTP-γ-S) and 5′-guanylyl-imidodiphosphate also inhibited motor pattern production. The possible sites of action of these guanine nucleotide analogues were examined to assess potential mechanisms by which they interfered with motor pattern production. Intracellular iontophoresis of GDP-β-S into C2 did not affect C2 basal synaptic strength. However, it did reduce heterosynaptic facilitation of C2 synapses caused by the dorsal swim interneurons (DSIs), a set of serotonergic swim CPG neurons. In contrast, GTP-γ-S directly enhanced C2 synaptic strength onto DFN, mimicking the neuromodulatory effect of the DSIs. GDP-β-S, but not the GTP analogues, decreased C2 excitability, whereas both GTP analogues, but not GDP-β-S, blocked the ability of DSI stimulation to increase C2 excitability. The decrease in C2 excitability caused by GDP-β-S is not likely to be responsible for the inhibition of the swim motor pattern because decreasing C2 firing rate, by injecting hyperpolarizing current, did not prevent the production of the rhythmic motor pattern. Taken together, these data suggest that G protein signaling is a necessary and integral component of the escape swim CPG in Tritonia and that G protein signaling mediates DSI heterosynaptic facilitation of C2 but may not mediate the DSI-evoked enhancement of C2 excitability.
OMP Gene Deletion Results in an Alteration in Odorant-Induced Mucosal Activity Patterns
Authors: Youngentob S. L. , Kent P. F. , Margolis F. L.
Published: May 2006

Previous behavioral work, using a complex five-odorant identification task, demonstrated that olfactory marker protein (OMP) is critically involved in odor processing to the extent that its loss results in an alteration in odorant quality perception. Exactly how the lack of OMP exerts its influence on the perception of odorant quality is unknown. However, there is considerable neurophysiological evidence that different odorants produce different spatiotemporal patterns of neural activity at the level of the mucosa and that these patterns predict the psychophysically determined perceptual relationship among odorants. In this respect, OMP gene deletion is known to result in a constellation of physiologic defects (i.e., marked reduction in the electroolfactogram (EOG) and altered response and recovery kinetics) that would be expected to alter the odorant-induced spatiotemporal activity patterns that are characteristic of different odorants. This, in turn, would be expected to alter the spatiotemporal patterning of information that results from the mucosal projection onto the bulb, thereby changing odorant quality perception. To test the hypothesis that odorant-induced mucosal activity patterns are altered in mice lacking the gene for OMP, we optically recorded the fluorescent changes in response to odorant stimulation from both the septum and turbinates of both OMP-null and control mice using a voltage-sensitive dye (di-4-ANEPPS Molecular Probes, Eugene, OR) and a Dalsa 120 × 120, 12-bit CCD camera. To maintain continuity with the previous behavioral work, the odorants 2-propanol, citral, carvone, ethylacetoacetate, and propyl acetate were again used. Each odorant was randomly presented to each mucosal surface in a Latin-Square design. The results of this study demonstrated that, for both mouse strains, there do indeed exist different spatiotemporal activity patterns for different odorants. More importantly, however, these patterns significantly differed between OMP-null and control mice. That is, although the general regions of characteristic activity for different odorants were the same in both mouse strains, the patterns in the null animals were degraded relative to controls. These data suggest therefore that the alterations in mucosal activity may serve as the substrate for the behaviorally observed changes in odorant quality perception in the null mutant.
Pontine Omnipause Activity During Conjugate and Disconjugate Eye Movements in Macaques
Authors: Busettini C. , Mays L. E.
Published: May 2006

Previous reports have shown that saccades executed during vergence eye movements are often slower and longer than conjugate saccades. Lesions in the nucleus raphe interpositus, where pontine omnipause neurons (OPNs) are located, were also shown to result in slower and longer saccades. If vergence transiently suppresses the activity of the OPNs just before a saccade, then reduced presaccadic activity might mimic the behavioral effects of a lesion. To test this hypothesis, 64 OPNs were recorded from 7 alert rhesus monkeys during smooth vergence and saccades with and without vergence. The firing rate of many OPNs was modulated by static vergence angle but not by version and showed transient changes during slow vergence without saccades. This modulation was smooth, and not the abrupt pause seen for saccades, indicating that OPNs do not act as gates for vergence commands. We confirmed that saccades made during both convergence and divergence are significantly slower and longer than conjugate saccades. OPNs paused for all saccades, and the pause lead (interval between pause onset and saccadic onset) was significantly longer for saccades with convergence, in agreement with our hypothesis. Contrary to our hypothesis, pause lead was not longer for saccades with divergence, even though these saccades were slowed as much as those occurring during convergence. Furthermore, there was no significant correlation, on a trial-by-trial basis, between pause lead and saccadic slowing. These results suggest that it is unlikely that presaccadic slowing of OPNs is responsible for the slower saccades seen during vergence movements.
Sodium Imaging of Climbing Fiber Innervation Fields in Developing Mouse Purkinje Cells
Authors: Scelfo Bibiana , Strata Piergiorgio , Knöpfel Thomas
Published: May 2006

Maturation of specific neuronal connections in the mature nervous system includes elimination of redundant synapses formed earlier during development. In the cerebellum of adult animals, each Purkinje cell (PC) is innervated by a single climbing fiber (CF). In early postnatal development each PC is innervated by multiple CFs and elimination of synapses formed by supernumerary CFs occurs until monoinnervation is established at around postnatal day 20 (P20) in mice. It is not clear whether multiple CFs, or only a single CF, translocate from the cell body of immature PCs to the developing dendrite and, in case several CFs translocate, whether they share or segregate their innervation fields. To localize CF innervation fields, we imaged changes in postsynaptic sodium concentration resulting from CF-mediated postsynaptic currents. We found that more than one CF translocates from an innervation field on the cell body of the PC to the developing dendrite and that these CFs share rather than segregate their innervation fields. We concluded that both the soma and the proximal dendrite of the PC are territories of competition for the developing CFs and that the overlapping of their termination fields may be the prerequisite for a local process of elimination of all but one CF, as previously demonstrated in the developing neuromuscular junction.
Reciprocal Interactions Between Calcium and Chloride in Rod Photoreceptors
Authors: Thoreson Wallace B. , Bryson Eric J. , Rabl Katalin
Published: May 2006

This study used imaging and electrophysiological techniques in salamander retinal slices to correlate Ca2+and Cl–levels in rods and thus test the hypothesis of a feedback interaction between Ca2+- and Ca2+-activated Cl–channels whereby Cl–efflux through Cl–channels can inhibit Ca2+channels. Increasing [K+]olevels produced a concentration-dependent depolarization of rods accompanied by increases in [Ca2+]imeasured with Fura-2. The voltage dependence of increases in [Ca2+]iwas compared with the voltage dependence of the calcium current ( ICa). [Cl–]iwas measured with the dye, MEQ. Depolarization with high K+to membrane potentials below –20 mV reduced [Cl–]i; larger depolarizations increased [Cl–]i. The Na/K/Cl cotransport inhibitor, bumetanide, shifted the apparent Cl–equilibrium potential ( ECl) to more negative potentials, suggesting that this cotransporter helps establish a relatively depolarized ECl. MEQ fluorescence changes evoked by high K+were inhibited by niflumic acid (0.1 mM), NPPB (2 μM), or replacement of Ca2+with Ba2+, suggesting that depolarization-evoked Cl–changes result partly from stimulation of Ca2+-activated Cl–channels. Replacing ≥12 mM [Cl–]owith CH3SO4–produced a significant reduction in [Cl–]i. [Ca2+]iincreases evoked by 20 or 50 mM K+were also significantly inhibited by replacing ≥12 mM [Cl–]owith CH3SO4–. Thus modest depolarization can evoke increases in [Ca2+]ithat lead to reductions in [Cl–]i, and conversely, reductions in [Cl–]iinhibit depolarization-evoked [Ca2+]iincreases. These findings support the hypothesis that feedback interactions between Ca2+- and Ca2+-activated Cl–channels may contribute to the regulation of presynaptic Ca2+currents involved in synaptic transmission from rod photoreceptors.
Binocular Deficits Associated With Early Alternating Monocular Defocus. II. Neurophysiological Observations
Authors: Zhang Bin , Matsuura Kazuki , Mori Takafumi , Wensveen Janice M. , Harwerth Ronald S. , Smith Earl L. , Chino Yuzo
Published: May 2006

Experiencing binocularly conflicting signals early in life dramatically alters the binocular responses of cortical neurons. Because visual cortex is highly plastic during a critical period of development, cortical deficits resulting from early abnormal visual experience often mirror the nature of interocular decorrelation of neural signals from the two eyes. In the preceding paper, we demonstrated that monkeys that experienced early alternating monocular defocus (–1.5, –3.0, or –6.0 D) show deficits in stereopsis that generally reflected the magnitude of imposed monocular defocus. Because these results indicated that alternating monocular defocus affected the higher spatial frequency components of visual scenes more severely, we employed microelectrode recording methods to investigate whether V1 neurons in these lens-reared monkeys exhibited spatial-frequency-dependent alterations in their binocular response properties. We found that a neuron's sensitivity to interocular spatial phase disparity was reduced in the treated monkeys and that this reduction was generally more severe for units tuned to higher spatial frequencies. In the majority of the affected units, the disparity-sensitivity loss was associated with interocular differences in monocular receptive field properties. The present results suggest that the behavioral deficits in stereopsis produced by abnormal visual experience reflect at least in part the constraints imposed by alterations at the earliest stages of binocular cortical processing and support the hypothesis that the local disparity processing mechanisms in primates are spatially tuned and can be independently compromised by early abnormal visual experience.
Spatial Sensitivity in Field PAF of Cat Auditory Cortex
Authors: Stecker G. Christopher , Mickey Brian J. , Macpherson Ewan A. , Middlebrooks John C.
Published: May 2006

We compared the spatial tuning properties of neurons in two fields [primary auditory cortex (A1) and posterior auditory field (PAF)] of cat auditory cortex. Broadband noise bursts of 80-ms duration were presented from loudspeakers throughout 360° in the horizontal plane (azimuth) or 260° in the vertical median plane (elevation). Sound levels varied from 20 to 40 dB above units' thresholds. We recorded neural spike activity simultaneously from 16 sites in field PAF and/or A1 of α-chloralose-anesthetized cats. We assessed spatial sensitivity by examining the dependence of spike count and response latency on stimulus location. In addition, we used an artificial neural network (ANN) to assess the information about stimulus location carried by spike patterns of single units and of ensembles of 2–32 units. The results indicate increased spatial sensitivity, more uniform distributions of preferred locations, and greater tolerance to changes in stimulus intensity among PAF units relative to A1 units. Compared to A1 units, PAF units responded at significantly longer latencies, and latencies varied more strongly with stimulus location. ANN analysis revealed significantly greater information transmission by spike patterns of PAF than A1 units, primarily reflecting the information transmitted by latency variation in PAF. Finally, information rates grew more rapidly with the number of units included in neural ensembles for PAF than A1. The latter finding suggests more accurate population coding of space in PAF, made possible by a more diverse population of neural response types.
Temporal Modulation of Scotopic Visual Signals by A17 Amacrine Cells in Mammalian Retina In Vivo
Authors: Dong Cun-Jian , Hare William A.
Published: May 2006

We examined function of the feedback pathway from A17 GABAergic amacrine cells to rod bipolar cells (A17 feedback), a critically located inhibitory circuit in the classic rod pathway of the mammalian retina whose role in processing of scotopic visual information is still poorly understood. We show evidence that this A17 feedback has a profound influence on the temporal properties of rod-driven postphotoreceptoral responses (assessed with the scotopic electroretinogram b-wave). Application of a GABAcantagonist prolonged preferentially the decay of the scotopic b-wave. The degree of prolongation increased as the light intensity decreased. Application of selective GABAa antagonists accelerated the kinetics of the scotopic b-wave. This effect was abolished when the GABAc antagonist was coapplied. Selective ablation of A17 cells mimicked the action of the GABAc antagonist. In A17 cell–ablated retinas, the GABAc antagonist was no longer very effective to slow the decay of the scotopic b-wave. Thus the A17 feedback, activated by light stimulation and mediated mainly by the GABAc receptors, makes the scotopic b-wave more transient by accelerating preferentially its decay. The strength of the feedback can be modulated by GABAa receptor–mediated inhibition and by light intensity. Our results also suggest that in the mammalian retina the feedback may be a novel mechanism that contributes postphotoreceptorally to the termination of rod signals, especially those elicited by very dim light stimuli.
Activity-Dependent Increase of the AHP Amplitude in T Sensory Neurons of the Leech
Authors: Scuri Rossana , Mozzachiodi Riccardo , Brunelli Marcello
Published: May 2006

We identified a new form of activity-dependent modulation of the afterhyperpolarization (AHP) in tactile (T) sensory neurons of the leech Hirudo medicinalis. Repetitive intracellular stimulation with 30 trains of depolarizing impulses at 15-s inter-stimulus interval (ISI) led to an increase of the AHP amplitude (∼60% of the control). The enhancement of AHP lasted for ≥15 min. The AHP increase was also elicited when a T neuron was activated by repetitive stimulation of its receptive field. The ISI was a critical parameter for the induction and maintenance of AHP enhancement. ISI duration had to fit within a time window with the upper limit of 20 s to make the training effective to induce an enhancement of the AHP amplitude. After recovery from potentiation, AHP amplitude could be enhanced once again by delivering another training session. The increase of AHP amplitude persisted in high Mg2+saline, suggesting an intrinsic cellular mechanism for its induction. Previous investigations reported that AHP of leech T neurons was mainly due to the activity of the Na+/K+ATPase and to a Ca2+-dependent K+current ( IK/Ca). In addition, it has been demonstrated that serotonin (5HT) reduces AHP amplitude through the inhibition of the Na+/K+ATPase. By blocking the IK/Cawith pharmacological agents, such as cadmium and apamin, we still observed an increase of the AHP amplitude after repetitive stimulation, whereas 5HT application completely inhibited the AHP increment. These data indicate that the Na+/K+ATPase is involved in the induction and maintenance of the AHP increase after repetitive stimulation. Moreover, the AHP increase was affected by the level of serotonin in the CNS. Finally, the increase of the AHP amplitude produced a lasting depression of the synaptic connection between two T neurons, suggesting that this activity-dependent phenomenon might be involved in short-term plasticity associated with learning processes.
Interneuronal Projections to Identified Cilia-Activating Pedal Neurons inHermissenda
Authors: Crow Terry , Tian Lian-Ming
Published: May 2006

Neural networks have been shown to support the generation of more than one behavioral motor act. In the nudibranch mollusk Hermissenda, Pavlovian conditioning results in light, the conditioned stimulus (CS), evoking both inhibition of locomotion and foot contraction. The synaptic organization of the eyes and optic ganglion is well documented; however, the characterization of the neural network mediating visually modulated behaviors is incomplete. We have now characterized synaptic connections between identified photoreceptors and a newly identified interneuron (IIb), identified synaptic projections from type I and type II interneurons to an inhibitory interneuron (IIIi) and to two newly identified pedal neurons, VP1 and VP2. Here we show that VP1 activates ciliary movement on the anterior foot and VP2 innervates the anterior foot and ventral tentacle. Stimulation of the photoreceptors with light produced two effects on the activity of VP1 and VP2. First, light inhibits type Iiand IIiinterneurons and disinhibits VP1 and VP2. Depolarization of type IIeinterneurons also disinhibits VP1 and VP2. Second, the light-elicited depolarization and increased tonic activity of VP1 and VP2 is produced by excitatory synaptic input from ipsilateral and contralateral type IIbinterneurons. Pedal neurons VP1 and VP2 receive similar synaptic input from type I, II, and IIIiinterneurons; this is in agreement with previous research showing that the visual pathway influences both ciliary locomotion and foot movement. The organization of the visual system in Hermissenda provides for the expression of cellular and synaptic plasticity supporting learning without altering the networks ability to carry out the requirements for normal visual processing.
Vagal Input to Lateral Area 3a in Cat Cortex
Authors: Ito Shin-Ichi , Craig A. D. (Bud)
Published: May 2006

Penfield's sensory homunculus included visceral organs at its lateral extreme, and vagal input was recently identified lateral to the intraoral representation in primary somatosensory cortex (S1) of rats. We tested whether vagal input is similarly located in cats where area 3b (equivalent to S1) is clearly distinguishable from adjacent regions. Field potentials were recorded from the intact dura over the left hemisphere using electrical stimulation of the left or right cervical vagus nerve in seven cats. A surface positive-negative potential was evoked from either side in the lateral part of the sigmoid gyrus. Finer mapping made at the pial surface with a microelectrode identified a focal site anteromedial to the anterior tip of the coronal sulcus. Depth recordings demonstrated polarity reversals and multi-unit vagal responses, indicating that the potentials were generated by an afferent activation focus in the middle layers of the cortex. The S1 mechanoreceptive representation was localized by mapping multi-unit somatosensory receptive fields in the middle cortical layers near the coronal sulcus. The vagal-evoked potential site was distinctly anterior to the intraoral S1 representation and adjacent to the masseteric-nerve-evoked potential focus. Lesions made at the focal site revealed that this site is cytoarchitectonically located in area 3a not area 3b. Thus vagal input to the sensorimotor cortex in cats resembles deep rather than cutaneous somatic input, similar to the localization of nociceptive-specific input to area 3a in monkeys. The possibilities are considered that this vagal input is involved in motor control and in the sensory experience of visceral afferent activity.
Long-Term Plasticity of Ipsilesional Medial Vestibular Nucleus Neurons After Unilateral Labyrinthectomy
Authors: Beraneck Mathieu , Hachemaoui Mohammed , Idoux Erwin , Ris Laurence , Uno Atsuhiko , Godaux Emile , Vidal Pierre-Paul , Moore Lee E. , Vibert Nicolas
Published: May 2006

Unilateral labyrinthectomy results in oculomotor and postural disturbances that regress in a few days during vestibular compensation. The long-term (after 1 mo) consequences of unilateral labyrinthectomy were investigated by characterizing the static and dynamic membrane properties of the ipsilesional vestibular neurons recorded intracellularly in guinea pig brain stem slices. We compared the responses of type A and type B medial vestibular nucleus neurons identified in vitro to current steps and ramps and to sinusoidal currents of various frequencies. All ipsilesional vestibular neurons were depolarized by 6–10 mV at rest compared with the cells recorded from control slices. Both their average membrane potential and firing threshold were more depolarized, which suggests that changes in active conductances compensated for the loss of excitatory afferents. The afterhyperpolarization and discharge regularity of type B but not type A neurons were increased. All ipsilesional vestibular cells became more sensitive to current injections over a large range of frequencies (0.2–30 Hz), but this increase in sensitivity was greater for type B than for type A neurons. This was associated with an increase of the peak frequency of linear response restricted to type B neurons, from 4–6 to 12–14 Hz. Altogether, we show that long-term vestibular compensation involves major changes in the membrane properties of vestibular neurons on the deafferented side. Many of the static and dynamic membrane properties of type B neurons became more similar to those of type A neurons than in control slices, leading to an increase in the overall homogeneity of medial vestibular nucleus neurons.
A Corollary Discharge Mechanism Modulates Central Auditory Processing in Singing Crickets
Authors: Poulet J.F.A. , Hedwig B.
Published: May 2006

Crickets communicate using loud (100 dB SPL) sound signals that could adversely affect their own auditory system. To examine how they cope with this self-generated acoustic stimulation, intracellular recordings were made from auditory afferent neurons and an identified auditory interneuron—the Omega 1 neuron (ON1)—during pharmacologically elicited singing (stridulation). During sonorous stridulation, the auditory afferents and ON1 responded with bursts of spikes to the crickets' own song. When the crickets were stridulating silently, after one wing had been removed, only a few spikes were recorded in the afferents and ON1. Primary afferent depolarizations (PADs) occurred in the terminals of the auditory afferents, and inhibitory postsynaptic potentials (IPSPs) were apparent in ON1. The PADs and IPSPs were composed of many summed, small-amplitude potentials that occurred at a rate of about 230 Hz. The PADs and the IPSPs started during the closing wing movement and peaked in amplitude during the subsequent opening wing movement. As a consequence, during silent stridulation, ON1's response to acoustic stimuli was maximally inhibited during wing opening. Inhibition coincides with the time when ON1 would otherwise be most strongly excited by self-generated sounds in a sonorously stridulating cricket. The PADs and the IPSPs persisted in fictively stridulating crickets whose ventral nerve cord had been isolated from muscles and sense organs. This strongly suggests that the inhibition of the auditory pathway is the result of a corollary discharge from the stridulation motor network. The central inhibition was mimicked by hyperpolarizing current injection into ON1 while it was responding to a 100 dB SPL sound pulse. This suppressed its spiking response to the acoustic stimulus and maintained its response to subsequent, quieter stimuli. The corollary discharge therefore prevents auditory desensitization in stridulating crickets and allows the animals to respond to external acoustic signals during the production of calling song.
Systemic and Pulmonary Effects of Vasopressors and Inotropes in the Neonate
Authors: Seri Istvan
Published: May 2006

This paper briefly reviews the systemic and pulmonary hemodynamic actions of the most frequently used vasopressor-inotropes and inotropes in the preterm and term neonate. It is important to note that very little is known about the medium- and long-term cardiovascular and neurodevelopmental benefits of the use of these medications in the neonate.
PSORS2 Markers Are Not Associated with Psoriatic Arthritis in the Italian Population
Authors: Giardina Emiliano , Predazzi Irene , Sinibaldi Cecilia , Peconi Cristina , Amerio Paolo , Costanzo Antonio , Paradisi Andrea , Capizzi Rodolfo , Paradisi Mauro , Chimenti Sergio , Taccari Egisto , Novelli Giuseppe
Published: May 2006

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy characterized by the association of arthritis and psoriasis (Ps). The precise etiology of PsA is unknown, but epidemiological studies supported the existence of a genetic component for the disease. Here we report an association study on a large PsA Italian cohort for DNA variants recently reported as associated alleles at PSORS2 (17q25) in Ps cohorts from the US. We focused on discovering a possible involvement of PSORS2 associated SNPs in pathogenesis of PsA. We selected two SNPs (rs7420, rs734232) within the proximal peak and two SNPs (rs869190 and rs1561946) within distal peak of PSORS2. Our results ruled out PSORS2 alleles as susceptibility factors in arthritis psoriatic patients of Italian origin and suggested that previous linkage signal reported for chromosome 17q25 should be independent on the presence of PsA.
Carotid Intima-Media Thickness in HIV-Infected Individuals: Relationship of Premature Atherosclerosis to Neuropsychological Deficits?
Authors: Yaldizli Özgür , Kastrup Oliver , Obermann Mark , Esser Stefan , Wilhelm Hans , Ley Christian , Diener Hans-Christoph , Maschke Matthias
Published: May 2006

Background: Intima-media thickness (IMT) measured by extracranial duplex sonography is a surrogate marker for atherosclerosis. It is well known that IMT is greater in HIV patients than in age-matched healthy controls due to HIV- induced endothelial damage and metabolic side-effects of antiretroviral therapy. However, it remains unclear whether atherosclerosis has an additional impact on cognitive function in HIV patients. Therefore, the objective of this study was to investigate the correlation between IMT and neuropsychological deficits in HIV patients. Methods: 47 HIV patients and 40 age-matched healthy controls were examined by extracranial ultrasound 2 and 3 cm before the flow divider to evaluate differences in IMT. Possible neuropsychological deficits in HIV patients were assessed using a battery of 10 neuropsychological tests. Results of neuropsychological tests and markers of disease severity were correlated with IMT in HIV patients. Results: IMT was significantly greater in patients than in healthy controls (p < 0.001). However, none of the neuropsychological tests correlated significantly with IMT measurements in HIV patients. There was only a weak correlation between deficits in attention and IMT in HIV patients (r = 0.44; p = 0.005), which was non-significant after correction for multiple comparisons. Markers of disease severity (CD4 cell count, HIV load in plasma, duration of HIV disease) did not correlate with IMT either. Conclusion: IMT was greater in HIV patients compared to age-matched controls but it appears that premature atherosclerosis has no additional impact on the evolution of neuropsychological deficits in HIV patients. IMT did not correlate with the severity of immunodeficiency.
Inhibition of Rat Renal Fibroblast Proliferation by Halofuginone
Authors: Haran Nurit , Leschinski Ludmila , Pines Mark , Rapoport Jayson
Published: May 2006

Background/Aim: Interstitial fibrosis is the final common pathway of renal damage and represents an important therapeutic target. Halofuginone is a nontoxic alkaloid, used as a coccidiostat, and is a potent inhibitor of collagen α1(I) and matrix metalloproteinase-2 (MMP-2) expression. We thus studied the effects of halofuginone on proliferation, collagen I synthesis, and MMP-2 activity of rat renal papillary fibroblasts in culture. Methods: Fibroblasts were isolated from rat renal papillae and studied during passages 3–4. The cell proliferation was studied in the presence of varying concentrations of halofuginone. The collagen synthesis was studied by [3H]proline uptake, before and after collagenase digestion, at varying concentrations of halofuginone. The MMP-2 activity was determined by zymography. The gelatinolytic activity was determined on gelatin-impregnated polyacrylamide gels containing samples of cell medium after incubation for 24 h with different halofuginone doses. Results: We studied a phenotype of papillary fibroblasts which stained positive for alpha smooth muscle actin. These cells are phenotypically myofibroblasts. Halufuginone inhibited the proliferation of these cells in a dose-related and reversible manner. Platelet-derived growth factor is known to stimulate fibroblast proliferation. Halofuginone at a concentration of 250 ng/ml almost completely abolished the effect of platelet-derived growth factor. It also almost completely inhibited the MMP-2 activity at doses of 250–350 ng/ml, as shown by zymography. Conclusions: Halofuginone exhibits antifibrotic effects in rat renal papillary fibroblasts in culture, in terms of inhibition of proliferation and inhibition of MMP-2. These findings could have therapeutic potential.
Assessment of neuromuscular and haemodynamic activity in individuals with and without chronic low back pain
Authors: McKeon Melissa D , Albert Wayne J , Neary J Patrick
Published: May 2006

Background

Biering-Sørenson (1984) found that individuals with less lumbar extensor muscle endurance had an increased occurrence of first episode low back pain. As a result, back endurance tests have been recommended for inclusion in health assessment protocols. However, different studies have reported markedly different values for endurance times, leading some researchers to believe that the back is receiving support from the biceps femoris and gluteus maximus. Therefore, this study was designed to examine the haemodynamic and neuromuscular activity of the erector spinae, biceps femoris, and gluteus maximus musculature during the Biering-Sørenson Muscular Endurance Test (BSME).

Methods

Seventeen healthy individuals and 46 individuals with chronic low back pain performed the Biering-Sørenson Muscular Endurance Test while surface electromyography was used to quantify neuromuscular activity. Disposable silver-silver-chloride electrodes were placed in a bipolar arrangement over the right or left biceps femoris, gluteus maximus, and the lumbosacral paraspinal muscles at the level of L3. Near Infrared Spectroscopy was used simultaneously to measure tissue oxygenation and blood volume changes of the erector spinae and biceps femoris.

Results

The healthy group displayed a significantly longer time to fatigue (Healthy: 168.5s, LBP: 111.1s; p ≤ 0.05). Significant differences were shown in the median frequency slope of the erector spinae between the two groups at 90–100% of the time to fatigue while no significant differences were noted in the haemodynamic data for the two groups.

Conclusion

Although the BSME has been recognized as a test for back endurance, individuals with chronic LBP appear to incorporate a strategy that may help support the back musculature by utilizing the biceps femoris and gluteus maximus to a greater degree than their healthy counterparts.
Group interpersonal psychotherapy for depression in rural Uganda: 6-month outcomes
Authors: Bass Judith , Neugebauer Richard , Clougherty Kathleen F. , Verdeli Helen , Wickramaratne Priya , Ndogoni Lincoln , Speelman Liesbeth , Weissman Myrna , Bolton Paul
Published: May 2006

Background

A randomised controlled trial comparing group interpersonal psychotherapy with treatment as usual among rural Ugandans meeting symptom and functional impairment criteria for DSM–IV major depressive disorder or sub-threshold disorder showed evidence of effectiveness immediately following the intervention.

Aims

To assess the long-term effectiveness of this therapy over a subsequent 6-month period.

Method

A follow-up study of trial participants was conducted in which the primary outcomes were depression diagnosis, depressive symptoms and functional impairment.

Results

At 6 months, participants receiving the group interpersonal psychotherapy had mean depression symptom and functional impairment scores respectively 14.0 points (95% CI 12.2–15.8; P < 0.0001) and 5.0 points (95% CI 3.6–6.4; P < 0.0001) lower than the control group. Similarly, the rate of major depression among those in the treatment arm (11.7%) was significantly lower than that in the control arm (54.9%) (P < 0.0001).

Conclusions

Participation in a 16-week group interpersonal psychotherapy intervention continued to confer a substantial mental health benefit 6 months after conclusion of the formal intervention.
Quality of Life Among Long-Term Adolescent and Adult Survivors of Childhood Cancer
Authors: Maunsell Elizabeth , Pogany Lisa , Barrera Maru , Shaw Amanda K. , Speechley Kathy N.
Published: May 2006

Purpose

We assessed effects of childhood or adolescent cancer on quality of life among adolescent and adult cancer survivors, a group who are thought to be at particular risk for adverse late effects.

Patients and Methods

We studied 1,334 survivors and 1,477 age- and sex-matched, general population controls from across Canada using a mailed questionnaire which included the Short Form-36 (SF-36) and measures of self-esteem, optimism, and life satisfaction. General linear models and logistic regression were used. Survivor-control differences corresponding to an effect size (ES) ≥ 0.5 were considered clinically important.

Results

Participants were age 15 years to 37 years. Most survivors (83.8%) were diagnosed ≥ 10 years earlier. Fewer survivors (62.1%) than controls (71.1%) reported very good or excellent general health (adjusted odds ratio, 0.6; 95% CI, 0.5 to 0.7). However, quality of life differences between survivors and controls were small, and for the most part probably not clinically important. Three clinical characteristics—having had CNS or bone cancer, more than one treatment series, and ≥ two organs with a dysfunction at treatment end—were independently associated with poorer quality of life in the physical dimensions. Only survivors with ≥ two organs with dysfunction (8.7%) reported poorer quality of life in both physical and psychosocial domains, with several clinically important ES. The largest ES for the SF-36 physical summary scores were found in the 8% of survivors with two or three of these characteristics simultaneously, compared with those survivors who had none (−0.79 and −1.13, respectively).

Conclusion

Overall, a sizeable majority of adolescent and adult long-term survivors of childhood cancer in Canada appear to have adapted well.
Loss of calcineurin Aα results in altered trafficking of AQP2 and in nephrogenic diabetes insipidus
Authors: Gooch J. L. , Guler R. L. , Barnes J. L. , Toro J. J.
Published: May 2006

The serine/threonine phosphatase calcineurin is an important signaling molecule involved in kidney development and function. One potential target of calcineurin action is the water channel aquaporin 2 (AQP2). In this study, we examined the effect of loss of calcineurin Aα (CnAα) on AQP2 function in vivo. CnAα null mice were found to have defective post-natal urine-concentrating ability and an impaired urine-concentrating response to vasopressin. Expression of AQP2 is normal but, paradoxically, vasopressin-mediated phosphorylation of the channel is decreased compared with wild-type littermates and there is no accumulation of AQP2 in the apical membrane. Calcineurin protein and activity was found in innermedullary collecting duct vesicles, and loss of calcineurin expression and activity was associated with a loss of AQP2 in the vesicle fraction. As such, the lack of vasopressin-mediated phosphorylation of AQP2 might be the result of a defect in normal trafficking of AQP2 to apical-targeted vesicles. Likewise, treatment of wild-type mice with cyclosporin A to inhibit calcineurin produces a similarly impaired urine-concentrating response to vasopressin and alterations in AQP2 phosphorylation and trafficking. These experiments demonstrate that, CnAα is required for normal intracellular trafficking of AQP2 and loss of calcineurin protein or activity disrupts AQP2 function.
Minority group members' theories of intergroup contact: A case study of British Muslims' conceptualizations of Islamophobia and social change
Authors: Hopkins Nick , Kahani‐Hopkins Vered
Published: May 2006

Much research in intergroup relations concerns the potential for interventions (e.g. intergroup contact) to reduce majorities' discrimination against minorities. In this paper we focus on how minority group members construe such interventions, especially as they affect their abilities to act in terms of their collective identity to realize social change. In addressing this issue, we focus on a minority's beliefs and theories concerning the intergroup dynamics lying behind their marginalization. Our data are qualitative and concern British Muslims' analyses of the dynamics of Islamophobia. Specifically, we explore two theorizations of Muslims' marginalization. Both share a concern with improving Muslims' collective position in Britain. However, they construe the dynamics to Islamophobia in very different ways, and this shapes their approach to intergroup contact and dialogue. Our analysis is informed by, and seeks to complement, social psychological theorizing on social change and intergroup contact.
Role of the Olivo-Cerebellar System in Timing
Authors: Xu Duo , Liu Tao , Ashe James , Bushara Khalafalla O.
Published: May 2006

Timing has been proposed as a basic function of the cerebellar cortex (particularly the climbing fiber afferents and their sole source, the inferior olive) that explains the contribution of the cerebellum to both motor control and nonmotor cognitive functions. However, whether the olivo-cerebellar system mediates time perception without motor behavior remains controversial. We used event-related functional magnetic resonance imaging to dissociate the neural correlates of the perceptual from the motor aspects of timing. The results show activation of multiple areas within the cerebellar cortex during both perception and motor performance of temporal sequences. The results further show that the inferior olive was activated only when subjects perceived the temporal sequences without motor activity. This finding is most consistent with electrophysiological studies showing decreased responsiveness of the inferior olivary neurons to sensory input during expected, self-produced movement. Our results suggest that the primary role of the inferior olive and the climbing fiber system in timing is the encoding of temporal information independent of motor behavior.
Mammalian Motoneuron Axon Targeting Requires Receptor Protein Tyrosine Phosphatases σ and δ
Authors: Uetani Noriko , Chagnon Mélanie J. , Kennedy Timothy E. , Iwakura Yoichiro , Tremblay Michel L.
Published: May 2006

The leukocyte common antigen-related (LAR) subfamily of receptor protein tyrosine phosphatases (RPTPs), LAR, RPTP-σ, and RPTP-δ, regulate neuroendocrine development, axonal regeneration, and hippocampal long-term potentiation in mammals. InDrosophila, RPTPs are required for appropriate axon targeting during embryonic development. In contrast, deletion of any one of the three LAR-RPTP family members in mammals does not result in gross axon targeting defects. Both RPTP-σ and RPTP-δ are highly expressed in the developing mammalian nervous system, suggesting they might be functionally redundant. To test this hypothesis, we generated RPTP-σ and RPTP-δ (RPTP-σ/δ) double-mutant mice. Although embryonic day 18.5 RPTP-σ and RPTP-δ single-mutant embryos were viable, RPTP-σ/δ double mutants were paralyzed, were never observed to draw a breath, and died shortly after cesarean section. RPTP-σ/δ double mutants exhibit severe muscle dysgenesis and severe loss of motoneurons in the spinal cord. Detailed analysis of the projections of phrenic nerves in RPTP-σ/δ double mutants indicated that these motoneuron axons emerge normally from the cervical spinal cord, but stall on reaching the diaphragm. Our results demonstrate that RPTP-σ and RPTP-δ complement each other functionally during mammalian development, and reveal an essential contribution of RPTP-σ and RPTP-δ to appropriate motoneuron axon targeting during mammalian axonogenesis.
The Detection of Salivary Minerals in Smokers and Non‐Smokers With Chronic Periodontitis by the Inductively Coupled Plasma‐Atomic Emission Spectrophotometry Technique
Authors: Erdemir Ebru Olgun , Erdemir Ali
Published: May 2006

Background: The purpose of this study was to evaluate the effect of smoking on the salivary minerals in subjects with chronic periodontitis by the inductively coupled plasma‐atomic emission spectrophotometry (ICP‐AES) technique.

Methods: The study group included 24 subjects–12 smokers and 12 non‐smokers–with chronic periodontitis. Clinical measurements and non‐stimulated whole saliva were obtained, and the levels of five elements–sodium, potassium, calcium, magnesium, and phosphate–in each specimen were analyzed.

Results: When the clinical parameters were compared between groups, only plaque index was significantly higher in smokers than non‐smokers (P <0.05). The mean plaque index of smokers and non‐smokers was 1.93 ± 0.51 and 1.51 ± 0.39, respectively. The results of this study showed that there were no significant differences between groups in the mineral content of saliva. In smokers, there were positive correlations between the levels of calcium, sodium, and magnesium and clinical attachment level. There was also a positive correlation between the level of phosphate and the percentage of bleeding on probing. In non‐smokers, there was a negative correlation only between the mean level of sodium and plaque index (P <0.05).

Conclusions: The present study showed that no significant differences were found between the mineral content of saliva of smokers and non‐smokers by the ICP‐AES technique. It is a useful, fast, and sensitive technique compared to other techniques, and it can be advised for researchers while analyzing the mineral content of saliva.
Hip Fracture Risk Among Community-Dwelling Elderly People in the United States: A Prospective Study of Physical, Cognitive, and Socioeconomic Indicators
Authors: Wilson Robin Taylor , Chase Gary A. , Chrischilles Elizabeth A. , Wallace Robert B.
Published: May 2006

Objectives. We determined risks of short-term (2-year) hip fracture in a nationally representative, prospective cohort of community-dwelling elderly people 70 years or older.

Methods. We used self-report data from 2 waves of the Asset and Health Dynamics Survey (n = 5630). Sample-weighted logistic regression analyses were conducted to determine risk of hip fracture in relation to several demographic, cognitive, physical, and socioeconomic indicators.

Results. During the 2-year study period, 102 participants reported a new hip fracture. Several indicators of physical functioning and cognitive status, including incorrect delayed word recall and inability to lift 10 lbs (4.5 kg), were significantly associated with hip fracture risk. In the final model, mobile home residents, individuals without Medicare part B insurance, and those without a high-school diploma were at more than a 2-fold risk of hip fracture. Educational level, physical functioning, and insurance status were the top 3 contributors to hip fracture risk.

Conclusions. In addition to functional status measures, health insurance status, educational level, and type of residence appear to be independent predictors of hip fracture.