bluuebunny/crossref_metadata_2025 huggingface dataset:
Do gap junctions play a role in nerve transmissions as well as pacing in mouse intestine?
Authors: Daniel E. E. , Yazbi Ahmed El , Mannarino Marco , Galante Gary , Boddy Geoffrey , Livergant Jonathan , Oskouei Tahereh Eteraf
Published: November 2006

Varicosities of nitrergic and other nerves end on deep muscular plexus interstitial cells of Cajal or on CD34-positive, c- kit-negative fibroblast-like cells. Both cell types connect to outer circular muscle by gap junctions, which may transmit nerve messages to muscle. We tested the hypotheses that gap junctions transmit pacing messages from interstitial cells of Cajal of the myenteric plexus. Effects of inhibitors of gap junction conductance were studied on paced contractions and nerve transmissions in small segments of circular muscle of mouse intestine. Using electrical field stimulation parameters (50 V/cm, 5 pps, and 0.5 ms) which evoke near maximal responses to nitrergic, cholinergic, and apamin-sensitive nerve stimulation, we isolated inhibitory responses to nitrergic nerves, inhibitory responses to apamin-sensitive nerves and excitatory responses to cholinergic nerves. 18β-Glycyrrhetinic acid (10, 30, and 100 μM), octanol (0.1, 0.3, and 1 mM) and gap peptides (300 μM of40Gap27,43Gap26,37,43Gap27) all failed to abolish neurotransmission. 18β-Glycyrrhetinic acid inhibited frequencies of paced contractions, likely owing to inhibition of l-type Ca2+channels in smooth muscle, but octanol or gap peptides did not. 18β-Glycyrrhetinic acid and octanol, but not gap peptides, reduced the amplitudes of spontaneous and nerve-induced contractions. These reductions paralleled reductions in contractions to exogenous carbachol. Additional experiments with gap peptides in both longitudinal and circular muscle segments after NG-nitro-l-arginine and TTX revealed no effects on pacing frequencies. We conclude that gap junction coupling may not be necessary for pacing or nerve transmission to the circular muscle of the mouse intestine.
Magnetic resonance imaging of progressive cardiomyopathic changes in the db/db mouse
Authors: Yue Patrick , Arai Takayasu , Terashima Masahiro , Sheikh Ahmad Y. , Cao Feng , Charo David , Hoyt Grant , Robbins Robert C. , Ashley Euan A. , Wu Joseph , Yang Phillip C. , Tsao Philip S.
Published: November 2006

The db/db mouse is a well-established model of diabetes. Previous reports have documented contractile dysfunction (i.e., cardiomyopathy) in these animals, although the extant literature provides limited insights into cardiac structure and function as they change over time. To better elucidate the natural history of cardiomyopathy in db/db mice, we performed cardiac magnetic resonance (CMR) scans on these animals. CMR imaging was conducted with a 4.7-T magnet on female db/db mice and control db/+ littermates at 5, 9, 13, 17, and 22 wk of age. Gated gradient echo sequences were used to obtain cineographic short-axis slices from apex to base. From these images left ventricular (LV) mass (LVM), wall thickness, end-diastolic volume (LVEDV), and ejection fraction (LVEF) were determined. Additionally, cardiac [18F]fluorodeoxyglucose ([18F]FDG) PET scanning, pressure-volume loops, and real-time quantitative PCR on db/db myocardium were performed. Relative to control, db/db mice developed significant increases in LVM and wall thickness as early as 9 wk of age. LVEDV diverged slightly later, at 13 wk. Interestingly, compared with the baseline level, LVEF in the db/db group did not decrease significantly until 22 wk. Additionally, [18F]FDG metabolic imaging showed a 40% decrease in glucose uptake in db/db mice. Furthermore, contractile dysfunction was observed in 15-wk db/db mice undergoing pressure-volume loops. Finally, real-time quantitative PCR revealed an age-dependent recapitulation of the fetal gene program, consistent with a myopathic process. In summary, as assessed by CMR, db/db mice develop characteristic structural and functional changes consistent with cardiomyopathy.
Lysophosphatidic acid induces endothelial cell death by modulating the redox environment
Authors: Brault Sonia , Gobeil Fernand , Fortier Audrey , Honoré Jean-Claude , Joyal Jean-Sébastien , Sapieha Przemyslaw S. , Kooli Amna , Martin Élodie , Hardy Pierre , Ribeiro-da-Silva Alfredo , Peri Krishna , Lachapelle Pierre , Varma Daya , Chemtob Sylvain
Published: November 2006

Oxidant stress plays a significant role in hypoxic-ischemic injury to the susceptible microvascular endothelial cells. During oxidant stress, lysophosphatidic acid (LPA) concentrations increase. We explored whether LPA caused cytotoxicity to neuromicrovascular cells and the potential mechanisms thereof. LPA caused a dose-dependent death of porcine cerebral microvascular as well as human umbilical vein endothelial cells; cell death appeared oncotic rather than apoptotic. LPA-induced cell death was mediated via LPA1receptor, because the specific LPA1receptor antagonist THG1603 fully abrogated LPA's effects. LPA decreased intracellular GSH levels and induced a p38 MAPK/JNK-dependent inducible nitric oxide synthase (NOS) expression. Pretreatment with the antioxidant GSH precursor N-acetyl-cysteine (NAC), as well as with inhibitors of NOS [ Nω-nitro-l-arginine (l-NNA); 1400W], significantly prevented LPA-induced endothelial cell death (in vitro) to comparable extents; as expected, p38 MAPK (SB203580) and JNK (SP-600125) inhibitors also diminished cell death. LPA did not increase indexes of oxidation (isoprostanes, hydroperoxides, and protein nitration) but did augment protein nitrosylation. Endothelial cytotoxicity by LPA in vitro was reproduced ex vivo in brain and in vivo in retina; THG1603, NAC, l-NNA, and combined SB-203580 and SP600125 prevented the microvascular rarefaction. Data implicate novel properties for LPA as a modulator of the cell redox environment, which partakes in endothelial cell death and ensued neuromicrovascular rarefaction.
Effect of acute activation of 5′-AMP-activated protein kinase on glycogen regulation in isolated rat skeletal muscle
Authors: Miyamoto Licht , Toyoda Taro , Hayashi Tatsuya , Yonemitsu Shin , Nakano Masako , Tanaka Satsuki , Ebihara Ken , Masuzaki Hiroaki , Hosoda Kiminori , Ogawa Yoshihiro , Inoue Gen , Fushiki Tohru , Nakao Kazuwa
Published: November 2006

5′-AMP-activated protein kinase (AMPK) has been implicated in glycogen metabolism in skeletal muscle. However, the physiological relevance of increased AMPK activity during exercise has not been fully clarified. This study was performed to determine the direct effects of acute AMPK activation on muscle glycogen regulation. For this purpose, we used an isolated rat muscle preparation and pharmacologically activated AMPK with 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleoside (AICAR). Tetanic contraction in vitro markedly activated the α1- and α2-isoforms of AMPK, with a corresponding increase in the rate of 3- O-methylglucose uptake. Incubation with AICAR elicited similar enhancement of AMPK activity and 3- O-methylglucose uptake in rat epitrochlearis muscle. In contrast, whereas contraction stimulated glycogen synthase (GS), AICAR treatment decreased GS activity. Insulin-stimulated GS activity also decreased after AICAR treatment. Whereas contraction activated glycogen phosphorylase (GP), AICAR did not alter GP activity. The muscle glycogen content decreased in response to contraction but was unchanged by AICAR. Lactate release was markedly increased when muscles were stimulated with AICAR in buffer containing glucose, indicating that the glucose taken up into the muscle was catabolized via glycolysis. Our results suggest that AMPK does not mediate contraction-stimulated glycogen synthesis or glycogenolysis in skeletal muscle and also that acute AMPK activation leads to an increased glycolytic flux by antagonizing contraction-stimulated glycogen synthesis.
Modified Sensory Processing in the Barrel Cortex of the Adult Mouse After Chronic Whisker Stimulation
Authors: Quairiaux Charles , Armstrong-James Michael , Welker Egbert
Published: November 2006

Chronic stimulation of a mystacial whisker follicle for 24 h induces structural and functional changes in layer IV of the corresponding barrel, with an insertion of new inhibitory synapses on spines and a depression of neuronal responses to the stimulated whisker. Under urethane anesthesia, we analyzed how sensory responses of single units are affected in layer IV and layers II & III of the stimulated barrel column as well as in adjacent columns. In the stimulated column, spatiotemporal characteristics of the activation evoked by the stimulated whisker are not altered, although spontaneous activity and response magnitude to the stimulated whisker are decreased. The sensitivity of neurons for the deflection of this whisker is not altered but the dynamic range of the response is reduced as tested by varying the amplitude and repetition rate of the deflection. Responses to deflection of nonstimulated whiskers remain unaltered with the exception of in-row whisker responses that are depressed in the column corresponding to the stimulated whisker. In adjacent nonstimulated columns, neuronal activity remains unaltered except for a diminished response of units in layer II/III to deflection of the stimulated whisker. From these results we propose that an increased inhibition within the stimulated barrel reduced the magnitude of its excitatory output and accordingly the flow of excitation toward layers II & III and the subsequent spread into adjacent columns. In addition, the period of uncorrelated activity between pathways from the stimulated and nonstimulated whiskers weakens synaptic inputs from in-row whiskers in the stimulated barrel column.
Reward Value Coding Distinct From Risk Attitude-Related Uncertainty Coding in Human Reward Systems
Authors: Tobler Philippe N. , O'Doherty John P. , Dolan Raymond J. , Schultz Wolfram
Published: November 2006

When deciding between different options, individuals are guided by the expected (mean) value of the different outcomes and by the associated degrees of uncertainty. We used functional magnetic resonance imaging to identify brain activations coding the key decision parameters of expected value (magnitude and probability) separately from uncertainty (statistical variance) of monetary rewards. Participants discriminated behaviorally between stimuli associated with different expected values and uncertainty. Stimuli associated with higher expected values elicited monotonically increasing activations in distinct regions of the striatum, irrespective of different combinations of magnitude and probability. Stimuli associated with higher uncertainty (variance) elicited increasing activations in the lateral orbitofrontal cortex. Uncertainty-related activations covaried with individual risk aversion in lateral orbitofrontal regions and risk-seeking in more medial areas. Furthermore, activations in expected value-coding regions in prefrontal cortex covaried differentially with uncertainty depending on risk attitudes of individual participants, suggesting that separate prefrontal regions are involved in risk aversion and seeking. These data demonstrate the distinct coding in key reward structures of the two basic and crucial decision parameters, expected value, and uncertainty.
Electrophysiological Differences Between Neurogliaform Cells From Monkey and Rat Prefrontal Cortex
Authors: Povysheva N. V. , Zaitsev A. V. , Kröner S. , Krimer O. A. , Rotaru D. C. , Gonzalez-Burgos G. , Lewis D. A. , Krimer L. S.
Published: November 2006

Current dogma holds that a canonical cortical circuit is formed by cellular elements that are basically identical across species. However, detailed and direct comparisons between species of specific elements of this circuit are limited in number. In this study, we compared the morphological and physiological properties of neurogliaform (NGF) inhibitory neurons in the prefrontal cortex (PFC) of macaque monkeys and rats. In both species, NGF cells were readily identified based on their distinctive morphological features. Indeed, monkey NGF cells had only a few morphological features that differed from rat, including a larger soma, a greater number of dendrites, and a more compact axonal field. In contrast, whole cell recordings of the responses to injected current steps revealed important differences between monkey and rat NGF cells. Monkey NGF cells consistently generated a short-latency first spike riding on an initial depolarizing hump, whereas in rat NGF cells, the first spike appeared after a substantial delay riding on a depolarizing ramp not seen in monkey NGF cells. Thus although rat NGF cells are traditionally classified as late-spiking cells, monkey NGF cells did not meet this physiological criterion. In addition, NGF cells in monkey appeared to be more excitable than those in rat because they displayed a higher input resistance, a lower spike threshold, and a higher firing frequency. Finally, NGF cells in monkey showed a more prominent spike-frequency adaptation as compared with rat. Our findings indicate that the canonical cortical circuit differs in at least some aspects of its constituent elements across species.
Response of Vestibular-Nerve Afferents to Active and Passive Rotations Under Normal Conditions and After Unilateral Labyrinthectomy
Authors: Sadeghi Soroush G. , Minor Lloyd B. , Cullen Kathleen E.
Published: November 2006

We investigated the possible contribution of signals carried by vestibular-nerve afferents to long-term processes of vestibular compensation after unilateral labyrinthectomy. Semicircular canal afferents were recorded from the contralesional nerve in three macaque monkeys before [horizontal (HC) = 67, anterior (AC) = 66, posterior (PC) = 50] and 1–12 mo after (HC = 192, AC = 86, PC = 57) lesion. Vestibular responses were evaluated using passive sinusoidal rotations with frequencies of 0.5–15 Hz (20–80°/s) and fast whole-body rotations reaching velocities of 500°/s. Sensitivities to nonvestibular inputs were tested by: 1) comparing responses during active and passive head movements, 2) rotating the body with the head held stationary to activate neck proprioceptors, and 3) encouraging head-restrained animals to attempt to make head movements that resulted in the production of neck torques of ≤2 Nm. Mean resting discharge rate before and after the lesion did not differ for the regular, D (dimorphic)-irregular, or C (calyx)-irregular afferents. In response to passive rotations, afferents showed no change in sensitivity and phase, inhibitory cutoff, and excitatory saturation after unilateral labyrinthectomy. Moreover, head sensitivities were similar during voluntary and passive head rotations and responses were not altered by neck proprioceptive or efference copy signals before or after the lesion. The only significant change was an increase in the proportion of C-irregular units postlesion, accompanied by a decrease in the proportion of regular afferents. Taken together, our findings show that changes in response properties of the vestibular afferent population are not likely to play a major role in the long-term changes associated with compensation after unilateral labyrinthectomy.
Contrast Gain Control Is Drift-Rate Dependent: An Informational Analysis
Authors: Hietanen M. A. , Crowder N. A. , Ibbotson M. R.
Published: November 2006

Neurons in the visual cortex code relative changes in illumination (contrast) and adapt their sensitivities to the visual scene by centering the steepest regions of their sigmoidal contrast response functions (CRFs: spike rate as a function of contrast) on the prevailing contrast. The influence of this contrast gain control has not been reported at nonoptimal drift rates. We calculated the Fisher information contained in the CRFs of halothane-anesthetized cats. Fisher information gives a measure of the accuracy of contrast representations based on the ratio of the square of the steepness of the CRF and the spike-rate dependency of the spiking variance. Variance increases with spike rate, so Fisher information is maximal where the CRF is steep and spike rates are low. Here, we show that the contrast at which the maximal Fisher information (CMFI) occurs for each adapting drift rate is at a fixed level above the adapting contrast. For adapting contrasts of 0 to 0.32 the relationship between CMFIand adapting contrast is well described by a straight line with a slope close to 1. The intercept of this line on the CMFI-axis is drift-rate dependent, although the slope is not. At high drift rates relative to each cell's peak the CMFIoffset is higher than that for low drift rates. The results show that the contrast coding strategy in visual cortex maximizes accuracy for contrasts above the prevailing contrast in the environment for all drift rates. We argue that tuning the system for accuracy at contrasts above the prevailing value is optimal for viewing natural scenes.
A Causal Role for Endothelin-1 in the Vascular Adaptation to Skeletal Muscle Deconditioning in Spinal Cord injury
Authors: Thijssen Dick H.J. , Ellenkamp Reinier , Kooijman Miriam , Pickkers Peter , Rongen Gerard A. , Hopman Maria T.E. , Smits Paul
Published: November 2006

Objective—

Endothelin-1 (ET-1) contributes to the increased peripheral resistance in heart failure and hypertension. Physical inactivity is associated with cardiovascular disease and characterized by increased vascular tone. In this study, we assess the contribution of ET-1 to the increased vascular tone in the extremely deconditioned legs of spinal cord-injured (SCI) individuals before and after exercise training.

Methods and Results—

In 8 controls and 8 SCI individuals, bilateral thigh blood flow was measured by plethysmography before and during the administration of an ET
A
/ET
B
-receptor blocker into the femoral artery. In SCI, this procedure was repeated after 6 weeks of electro-stimulated training. In a subset of SCI (n=4), selective ET
A
-receptor blockade was performed to determine the role of the ET
A
-receptors. In controls, dual ET-receptor blockade increased leg blood flow at the infused side (10%,
P
<0.05), indicating a small contribution of ET-1 to leg vascular tone. In SCI, baseline blood flow was lower compared with controls (
P
=0.05). In SCI, dual ET-receptor blockade increased blood flow (41%,
P
<0.001). This vasodilator response was significantly larger in SCI compared with controls (
P
<0.001). The response to selective ET
A
-receptor blockade was similar to the effect of dual blockade. Electro-stimulated training normalized baseline blood flow in SCI and reduced the response to dual ET-receptor blockade in the infused leg (29%,
P
=0.04).

Conclusion—

ET-1 mediates the increased vascular tone of extremely inactive legs of SCI individuals by increased activation of ET
A
-receptors. Physical training reverses the ET-1-pathway, which normalizes basal leg vascular tone.
Genome-Wide Linkage Scan of Common Stroke in Families From Northern Sweden
Authors: Nilsson-Ardnor Sofie , Janunger Tomas , Wiklund Per-Gunnar , Lackovic Kurt , Nilsson Anna Karin , Lindgren Petter , Escher Stefan A. , Stegmayr Birgitta , Asplund Kjell , Holmberg Dan
Published: November 2006

Background and Purpose—

Taking advantage of low genetic variations in northern Sweden, we performed a genome-wide linkage scan to investigate the susceptibility loci for common forms of stroke.

Methods—

Fifty-six families, containing multiple cases of stroke and whose data had been previously used to replicate linkage to the phosphodiesterase 4D locus on chromosome 5q, were genotyped in a genome-wide scan. Fine mapping was performed, and subsequently 53 additional families from the same region were genotyped over the candidate regions.

Results—

Linkage calculations were performed by using 3 different disease models, from a very broad (all stroke cases defined by World Health Organization MONICA criteria) to a narrower (ischemic stroke only) stroke phenotype. With all models, nonparametric multipoint linkage analysis yielded allele-sharing log of the odds (LOD) scores >1.2 at 9 locations: 1p34, 5q13, 7q35, 9q22, 9q34, 13q32, 14q32, 18p11, and 20q13. The highest allele-sharing LOD scores were obtained on chromosomes 5q (previously reported), 1p (LOD=2.09), and 18p (LOD=2.14). Fine mapping resulted in increased allele-sharing LOD scores for chromosome 5q (previously reported) and 9q22 (LOD=1.56), but all others decreased. Combining these initial results with a subsequent analysis of 53 additional families, we obtained the highest allele-sharing LOD scores on chromosomes 5q, 13q, and 18p, although none reached the initial genome-wide allele-sharing LOD scores.

Conclusions—

Genetic analysis of stroke in families from northern Sweden did not identify any new major stroke loci. This indicates that multiple minor susceptibility loci in addition to the previously known locus on chromosome 5 could contribute to the disease.
Asymptomatic Hemorrhage After Thrombolysis May Not Be Benign
Authors: Dzialowski Imanuel , Pexman J. H. Warwick , Barber Philip A. , Demchuk Andrew M. , Buchan Alastair M. , Hill Michael D.
Published: November 2006

Background and Purpose—

There is ongoing controversy about the impact of hemorrhagic transformation after thrombolysis on long-term functional outcome. We sought to study the relation between the type of hemorrhagic transformation on CT scans and functional outcome.

Methods—

Data were obtained from the Canadian Alteplase for Stroke Effectiveness Study. This study was established as a registry to prospectively collect data for acute stroke patients receiving intravenous alteplase within 3 hours from stroke onset between February 1999 and June 2001. Follow-up was completed at 90 days, and good functional outcome was defined as a modified Rankin Scale score of 0 or 1. Copies of head CT scans obtained at 24 to 48 hours after starting treatment were read in consensus by a central reading panel consisting of 1 neuroradiologist and 1 stroke neurologist. According to European Cooperative Acute Stroke Study criteria, hemorrhagic transformation was classified as none, hemorrhagic infarction (HI-1 and HI-2), or parenchymal hematoma (PH-1 and PH-2). We compared outcome across groups and performed a multivariable analysis including previously determined important predictors of good outcome in acute ischemic stroke.

Results—

From 1135 patients enrolled at 60 centers across Canada, 954 follow-up CT scans were assessable. We observed some hemorrhagic transformation in 259 of 954 (27.1%) patients (110 HI-1, 57 HI-2, 48 PH-1, and 44 PH-2). Proportions of patients with good outcome were 41% with no hemorrhagic transformation, 30% with HI-1, 17% with HI-2, 15% with PH-1, and 7% with PH-2 (
P
<0.0001, χ
2
test). After adjustment for age, baseline serum glucose, baseline Alberta Stroke Program Early CT score, and baseline National Institutes of Health Stroke Scale score, HI-1 was not a predictor of outcome. However, HI-2 (odds ratio=0.38, 95% CI=0.17 to 0.83), PH-1 (odds ratio=0.32, 95% CI=0.12 to 0.80), and PH-2 (odds ratio=0.14, 95% CI=0.04 to 0.48) were all negative predictors of outcome.

Conclusions—

The likelihood of a poor outcome after thrombolysis was proportional to the extent of hemorrhage on CT scans. HI grades of hemorrhagic transformation may not be benign.
Effects of Splinting on Wrist Contracture After Stroke
Authors: Lannin Natasha A. , Cusick Anne , McCluskey Annie , Herbert Robert D.
Published: November 2006

Background and Purpose—

Splints are commonly applied to the wrist and hand to prevent and treat contracture after stroke. However, there have been few randomized trials of this intervention. We sought to determine whether wearing a hand splint, which positions the wrist in either a neutral or an extended position, reduces wrist contracture in adults with hemiplegia after stroke.

Methods—

Sixty-three adults who had experienced a stroke within the preceding 8 weeks participated. They were randomized to either a control group (routine therapy) or 1 of 2 intervention groups (routine therapy plus splint in either a neutral or an extended wrist position). Splints were worn overnight for, on average, between 9 and 12 hours, for 4 weeks. The primary outcome, measured by a blinded assessor, was extensibility of the wrist and long finger flexor muscles (angle of wrist extension at a standardized torque).

Results—

Neither splint appreciably increased extensibility of the wrist and long finger flexor muscles. After 4 weeks, the effect of neutral wrist splinting was to increase wrist extensibility by a mean of 1.4° (95% CI, −5.4° to 8.2°), and splinting the wrist in extension reduced wrist extensibility by a mean of 1.3° (95% CI, −4.9° to 2.4°) compared with the control condition.

Conclusions—

Splinting the wrist in either the neutral or extended wrist position for 4 weeks did not reduce wrist contracture after stroke. These findings suggest that the practice of routine wrist splinting soon after stroke should be discontinued.
Pharmacological Induction of Ischemic Tolerance by Glutamate Transporter-1 (EAAT2) Upregulation
Authors: Chu Kon , Lee Soon-Tae , Sinn Dong-In , Ko Song-Yi , Kim Eun-Hee , Kim Jeong-Min , Kim Se-Jeong , Park Dong-Kyu , Jung Keun-Hwa , Song Eun-Cheol , Lee Sang Kun , Kim Manho , Roh Jae-Kyu
Published: November 2006

Background and Purpose—

Astrocytic glutamate transporter protein, GLT-1 (EAAT2), recovers extracellular glutamate and ensures that neurons are protected from excess stimulation. Recently, β-lactam antibiotics, like ceftriaxone (CTX), were reported to induce the upregulation of GLT-1. Here, we investigated ischemic tolerance induction by CTX in an experimental model of focal cerebral ischemia.

Methods—

CTX (200 mg/kg per day, IP) was administered for 5 consecutive days before transient focal ischemia, which was induced by intraluminal thread occlusion of the middle cerebral artery for 90 minutes or permanently.

Results—

Repeated CTX injections enhanced GLT-1 mRNA and protein expressions after 3 and 5 days of treatment, respectively. CTX-pretreated animals showed a reduction in infarct volume by 58% (reperfusion) and 39% (permanent), compared with the vehicle-pretreated animals at 24 hours postischemia (
P
<0.01). Lower doses of CTX (20 mg/kg per day and 100 mg/kg per day) reduced infarct volumes to a lesser degree. The injection of GLT-1 inhibitor (dihydrokainate) at 30 minutes before ischemia ameliorated the effect of CTX pretreatment. However, CTX administration at 30 minutes after ischemia produced no significant reduction in infarct volume. CTX reduced the levels of proinflammatory cytokines (tumor necrosis factor-α, FasL), matrix metalloproteinase (MMP)-9, and activated caspase-9 (
P
<0.01). In addition, CTX-pretreated animals showed better functional recovery at day 1 to week 5 after ischemia (
P
<0.05).

Conclusions—

This study presents evidence that CTX induces ischemic tolerance in focal cerebral ischemia and that this is mediated by GLT-1 upregulation.
Serial Diffusion Tensor MRI After Transient and Permanent Cerebral Ischemia in Nonhuman Primates
Authors: Liu Yutong , D’Arceuil Helen E. , Westmoreland Susan , He Julian , Duggan Michael , Gonzalez R. Gilberto , Pryor Johnny , Crespigny Alex J. de
Published: November 2006

Background and Purpose—

We measured the temporal evolution of the T2 and diffusion tensor imaging parameters after transient and permanent cerebral middle cerebral artery occlusion (MCAo) in macaques, and compared it to standard histological analysis at the study end point.

Methods—

Stroke was created in adult male macaques by occluding a middle cerebral artery branch for 3 hours (transient MCAo, n=4 or permanent occlusion, n=3). Conventional MRI and diffusion tensor imaging scans were performed 0 (acute day), 1, 3, 7, 10, 17, and 30 days after MCAo. Animals were euthanized after the final scan and the brains removed for histological analysis.

Results—

Apparent diffusion coefficient in the lesion was decreased acutely, fractional anisotropy was elevated, and T2 remained normal. Thereafter, apparent diffusion coefficient increased above normal, fractional anisotropy decreased to below normal, T2 increased to a maximum and then declined. Reperfusion at 3 hours accelerated these MRI changes. Only the fractional anisotropy value was significantly different between transient and permanent groups at 30 days. Final MRI-defined fractional lesion volumes were well correlated with corresponding histological lesion volumes. Permanent MCAO animals showed more severe histological damage than their transient MCAO counterparts, especially myelin damage and axonal swelling.

Conclusions—

Overall, the MRI evolution of stroke in macaques was closer to what has been observed in humans than in rodent models. This work supports the use of serial MRI in stroke studies in nonhuman primates.
Endovascular Treatment of Experimental Aneurysms by Use of Fibroblast-Coated Platinum Coils
Authors: Dai Daying , Ding Yong Hong , Danielson Mark A. , Kadirvel Ramanathan , Hunter Larry W. , Zhan Wen-Zhi , Helm Gregory A. , Lewis Debra A. , Cloft Harry J. , Sieck Gary C. , Kallmes David F.
Published: November 2006

Background and Purpose—

The purpose of this study was to determine whether implanting exogenous fibroblasts on platinum coils could enhance intra-aneurysmal fibrosis. Hypotheses included: (1) fibroblast-coated (FBC) platinum coils can improve angiographic results after embolization; and (2) FBC platinum coils can accelerate histological healing of embolized aneurysms.

Methods—

Experimental aneurysms in rabbits were embolized with control platinum coils (n=18) or FBC coils (n=18). Subjects were euthanized at 14 days, 1 month, 3 months and 6 months after implantation. Digital subtraction angiography was used to evaluate stability after embolization. Histological samples were examined with a grading system (range, 0 to 12) based on neck and dome healing.

Results—

Histology total scores and fibrosis ratio at 14 days were significantly greater in the FBC coil group compared with controls (6.6±1.9 versus 2.5±1.1, 1.2±0.6% versus 0.2±0.3%, respectively;
P
=0.0090). Cavities embolized with FBC coils showed cellular proliferation and thrombus organization, with an endothelialized membrane bridging the neck. There were no differences between groups in the later timepoints. The FBC coil group showed radiographic stability in 11 (61%) cases, coil compaction in 2 (11%) cases, and progressive occlusion in 5 (28%) cases. No progressive occlusion was seen in controls; 3 (17%) of 18 control cases exhibited coil compaction (
P
=0.0546).

Conclusions—

FBC coils can accelerate early histological healing compared with control coils in the rabbit aneurysm model.
MRI Monitoring of Neuroinflammation in Mouse Focal Ischemia
Authors: Wiart Marlène , Davoust Nathalie , Pialat Jean-Baptiste , Desestret Virginie , Moucharrafie Samir , Cho Tae-Hee , Mutin Mireille , Langlois Jean-Baptiste , Beuf Olivier , Honnorat Jérôme , Nighoghossian Norbert , Berthezène Yves
Published: November 2006

Background and Purpose—

A growing body of evidence suggests that inflammatory processes are involved in the pathophysiology of stroke. Phagocyte cells, involving resident microglia and infiltrating macrophages, secrete both protective and toxic molecules and thus represent a potential therapeutic target. The aim of the present study was to monitor phagocytic activity after focal cerebral ischemia in mice.

Methods—

Ultrasmall superparamagnetic particles of iron oxide (USPIO) were intravenously injected after permanent middle cerebral artery occlusion and monitored by high resolution MRI for 72 hours.

Results—

We here present the first MRI data showing in vivo phagocyte-labeling obtained in mice with focal cerebral ischemia. USPIO-enhanced MRI kinetic analysis disclosed an inflammatory response surrounding the ischemic lesion and in the contralateral hemisphere via the corpus callosum. The imaging data collected during the first 36 hours postinjury suggested a spread of USPIO-related signal from ipsi- to contralateral hemisphere. Imaging data correlated with histochemical analysis showing inflammation remote from the lesion and ingestion of nanoparticles by microglia/macrophages.

Conclusions—

The present study shows that MR-tracking of phagocyte cells is feasible in mice, which may have critical therapeutic implications given the potential neurotoxicity of activated microglia/macrophages in central nervous system disorders.
The Trabecula cranii: development and homology of an enigmatic vertebrate head structure
Authors: Cerny Robert , Horáček Ivan , Olsson Lennart
Published: November 2006

The vertebrate cranium consists of three parts: neuro-, viscero- and dermatocranium, which differ in both developmental and phylogenetic origin. Traditionally, developmental origin has been used as a criterion for homology, but this becomes problematic when skull elements such as the parietal bone are now shown, by modern fate-mapping studies, to have different developmental origins in different groups of tetrapods. This indicates a flexibility of developmental programmes and regulatory pathways which has probably been very important in cranial evolution. The trabecula cranii is an intriguing cranial element in the anterior cranial base in vertebrates. It forms a viscerocranial part of the neurocranium and is believed to be neural crest-derived in gnathostomes, but a similarly named structure in lampreys has been shown to have a mesodermal origin. Topographically, this trabecula seems to be homologous to the gnathostome trabecula cranii, and might also have the same function: to form a border between adjacent morphogenetic domains, to constrain and redirect growth of both brain and stomodeum and thus to refine developmental schedules of both. We suggest that such a border zone can recruit cells from either the mesoderm (as in the lamprey) or from the neural crest (as in the gnathostomes investigated), and still retain its homology. In our view, the trabecula is an interface element that integrates the respective divergent morphogenetics programs of the preotic head into a balanced unit; we suggest that such a definition can be used to define "the sameness" of this element throughout vertebrates.
Out of place and out of time – towards a more integrated approach to heterochrony
Authors: Spicer John , Rundle Simon
Published: November 2006

Heterochrony (changes in the relative timing of development between species) has been studied almost exclusively using morphological characters, with a focus on changes in size and shape (as a surrogate for time) between ancestral species and their descendents. Such an approach is restrictive in that it precludes the investigation of heterochronies in other, non-morphological traits and, therefore, hampers a more integrated approach to heterochrony. Such an integrated approach, where cellular, molecular and genetic approaches are used within a comparative phylogenetic framework to investigate developmental sequences, has been advocated by workers such as Smith and Raff. Here we suggest that equal emphasis should be given to the importance of physiological and ecological mechanisms that relate to changes in developmental sequence. Reviews of the history and status of physiological and ecological heterochrony reveal several examples for each, although progress has been hampered to some degree by a lack of recognition of physiological heterochrony and a lack of mechanistic understanding (heterochronies in evolutionary ecology). What emerges is that each discipline potentially brings something quite different, and complementary, to the study of heterochrony. The emergence of physiological heterochrony has arguably put the emphasis back on the object of selection and how the developing organism works: studies relating ecology and heterochrony have sought to establish whether or not there is an adaptive basis to altered sequences. We propose that any future studies of heterochrony should seek to exploit these different strengths rather than see them as merely complementary approaches.
Peptides and proteins regulating food intake: a comparative view
Authors: Gorissen Marnix , Flik Gert , Huising Mark
Published: November 2006

Energy homeostasis is under multiple endocrine and neural controls that involve both central and peripheral hormones and neuropeptides. Disorders of energy balance (e.g., obesitas and anorexia nervosa) are caused by subtle dysregulation of these regulatory mechanisms. The hypothalamic arcuate nucleus is a main site of central regulation where two distinct subpopulations of neurons co-express either neuropeptide Y (NPY) and agouti-related protein (AgRP), or proopiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART): the former set of peptides increases food intake; the latter decreases food intake and affect energy metabolism. Key peripheral hormones affecting energy metabolism include cholecystokinin (CCK), leptin and insulin, which decrease food intake, and ghrelin, which increases food intake. CCK and ghrelin regulate food intake in the short term (by affecting meal size), whereas leptin and insulin regulate food intake over longer periods spanning several meals. These signals and their physiology are reasonably well understood in mammals. On the other hand, knowledge on energy metabolism in earlier vertebrates is scant. Recently characterised central food intake regulatory mechanisms in fish suggest that they operate in a manner similar to their mammalian counterparts. Peripheral mechanisms have been poorly studied outside mammals. The recent identification of leptin in several fish species provides new insights and opportunities to enhance our understanding of the regulation of food intake. Comparative analysis of these peripheral mechanisms may shed new light on the function and evolution of the mechanisms controlling energy homeostasis. In this review, we summarise recent developments in understanding of mechanisms and signals that regulate energy balance in mammals, and compare these to what we now know about their orthologues in earlier vertebrates, with a particular focus on bony fishes.
Does Negotiation Have a Future in Controlling Weapons of Mass Destruction?
Authors: Jensen Lloyd
Published: November 2006

Despite the heightened level of concern about weapons of mass destruction since 9/11, negotiations for strengthening the WMD nonproliferation regime have been somewhat less than productive. The fact that the material and technology for producing such weapons is also used for peaceful purposes helps explain the limited progress. Lack of trust, concern about equality and fairness as well as the tendency to use negotiations for ulterior purposes also make progress difficult. After considering these points, the article discusses some of the incentives and disincentives that have been used to influence positions on the nonproliferation issue and how paying attention to the needs and interests of the would-be proliferators might increase the chances of reaching mutually beneficial agreements.
The Logic of a Soft Intervention Strategy: The United States and Conflict Conciliation in Africa
Authors: Rothchild Donald
Published: November 2006

What forms of U.S. intervention are likely to prove realizable and to be appropriate for facilitating the implementation of peace agreements and protecting human rights in Africa? The choices for action are certainly wider than the polar opposites of disengagement and large-scale military intervention. Because the United States can afford neither prolonged military hegemony nor the indulgence of neo-isolationism, it must find some form of creative engagement that fulfills its obligations to facilitate and protect in ways that are acceptable to both American and overseas opinion. Limited interests in Africa and the nature of public pressures leave little alternative to utilizing soft intervention approaches in most cases. Within the category of soft intervention, there appears to be a continuum of means leading to possible movement into muscular intervention. At one end, there is coercive diplomacy, which is associated with threats of military and economic sanctions; if these sanctions are actually used, the intervening state becomes involved in muscular intervention. At the other end is diplomacy associated not with threats, but with the promise of rewards. Between the two poles lies diplomacy that involves neither threats nor rewards (i.e., conciliation and mediation without the use of pressures and incentives). In real world contexts, third parties tend to apply mixed packages of non-coercive and coercive incentives, with coercive incentives becoming increasingly dominant as the costs of altering preferences and the intensity of conflict rise.
Group Attachments in Negotiation and Collective Action
Authors: Druckman Daniel
Published: November 2006

The impact of group attachments on negotiating behavior is a theme (or variable) that runs through many articles published in International Negotiation. It is also a popular topic for research on groups reported in other outlets. This literature set in motion the analytical probe discussed in this article. Focusing attention primarily on ingroup-favoring biases, four questions are asked: What is the phenomenon? Why does it occur? How can it be reduced? Where is it manifest in a larger policy context within which negotiations take place? Highlighted in this essay are the prevalence of the bias, the variety of plausible explanations for its occurrence, the distinction between patriotic and nationalistic group attachments, and the connections between group loyalty, policy making, and collective action. The insights achieved also reveal a number of areas for further research. This topic is one example of the many research accomplishments that herald the birth and maturity of a field of study and practice. In this special issue, we take pause to document these accomplishments as we look forward to another decade of progress.
Doped ZnO Nanowires Obtained by Thermal Annealing
Authors: Shan C. X. , Liu Z. , Wong C. C. , Hark S. K.
Published: November 2006

Doped ZnO nanowires were prepared in a very simple and inexpensive thermal annealing method using ZnSe nanowires as a precursor. As doped, P doped, and As/P codoped ZnO nanowires were obtained in this method. X-ray diffraction shows that the zincblende ZnSe nanowires were converted
to doped wurtzite ZnO nanowires. The incorporation of the dopants was confirmed by energy dispersive X-ray spectroscopy. The doping concentration could be adjusted by changing the annealing temperature and duration. Scanning electron microscopy indicated that the morphology of the ZnSe nanowires
was essentially retained after the annealing and doping process. Photoluminescence spectroscopy also verified the incorporation of the dopants into the nanowires.
Mechanical Characterization of Cellulosic Thecal Plates in Dinoflagellates by Nanoindentation
Authors: Lau Ringo K. L. , Kwok Alvin C. M. , Chan W. K. , Zhang T. Y. , Wong Joseph T. Y.
Published: November 2006

Dinoflagellates constitute an important group of microorganisms. Symbiotic dinoflagellates are responsible for the primary production of coral reef ecosystems and the phenomenon of their demise is known as "coral bleaching." Blooming of the planktonic dinoflagellates is the major cause
of "red tides." Many dinoflagellates have prominent membrane-bound thecal plates at their cell cortices. These thecal plates have high cellulose content and are biologically fabricated into various shapes. However, the mechanical properties of theca have not previously been characterized;
understanding these properties, including hardness and elastic modulus, will give insights into the ecological significance and biotechnological potential of bio-fabricated structures. A series of nanoindentation tests were performed on various locations of cellulosic thecal plates isolated
from the dinoflagellates Alexandrium catenella and Lingulodinium polyedrum.2 Despite having transparent properties, thecal plates possess mechanical properties comparable to softwood cell walls, implicating their role as a protective cell covering. Consistent measurements were
obtained when indentation was performed at various locations, which contrasts with the high variability of cellulose microfibers from plant sources. The present study demonstrated the novel properties of this potential new source of cellulose.
Electromagnetic Interference Shielding Characteristics of Carbon Nanofiber-Polymer Composites
Authors: Yang Yonglai , Gupta Mool C. , Dudley Kenneth L. , Lawrence Roland W.
Published: November 2006

Electromagnetic interference (EMI) shielding characteristics of carbon nanofiber-polystyrene composites were investigated in the frequency range of 12.4–18 GHz (Ku-band). It was observed that the shielding effectiveness of such composites was frequency independent, and increased
with increasing carbon nanofiber loading within Ku-band. The experimental data exhibited that the shielding effectiveness of the polymer composite containing 20 wt% carbon nanofibers could reach more than 36 dB in the measured frequency region, indicating such composites can be applied to
the potential EMI shielding materials. In addition, the results showed that the contribution of reflection to the EMI shielding effectiveness was much larger than that of absorption, implying the primary EMI shielding mechanism of such composites was reflection of electromagnetic radiation
within Ku-band.
Carbon Nanotube Reinforced Aluminum Nanocomposite via Plasma and High Velocity Oxy-Fuel Spray Forming
Authors: Laha T. , Liu Y. , Agarwal A.
Published: November 2006

Free standing structures of hypereutectic aluminum-23 wt% silicon nanocomposite with multiwalled carbon nanotubes (MWCNT) reinforcement have been successfully fabricated by two different thermal spraying technique viz Plasma Spray Forming (PSF) and High Velocity Oxy-Fuel (HVOF) Spray
Forming. Comparative microstructural and mechanical property evaluation of the two thermally spray formed nanocomposites has been carried out. Presence of nanosized grains in the Al–Si alloy matrix and physically intact and undamaged carbon nanotubes were observed in both the nanocomposites.
Excellent interfacial bonding between Al alloy matrix and MWCNT was observed. The elastic modulus and hardness of HVOF sprayed nanocomposite is found to be higher than PSF sprayed composites.
Analysis of Stress Responsive Genes Induced by Single-Walled Carbon Nanotubes in BJ Foreskin Cells
Authors: Sarkar Shubhashish , Sharma Chidananda , Yog Rajeshwari , Periakaruppan Adaikkappan , Jejelowo Olufisayo , Thomas Renard , Barrera Enrique V. , Rice-Ficht Allison C. , Wilson Bobby L. , Ramesh Govindarajan T.
Published: November 2006

Nanotechnology is finding its use as a potential technology in consumer products, defense, electronics, and medical applications by exploiting the properties of nanomaterials. Single-walled carbon nanotubes are novel forms of these nanomaterials with potential for large applications.
However, the toxicity studies on this material are not explored in detail and therefore limiting its use. It has been earlier reported that single-walled carbon nanotubes induces oxidative stress and also dictates activation of specific signaling pathway in keratinocytes. The present study
explores the effect of single-walled carbon nanotubes on stress genes in human BJ Foreskin cells. The results show induction of oxidative stress in BJ Foreskin cells by single-walled carbon nanotubes and increase in stress responsive genes. The genes included inducible genes like HMOX1, HMOX2,
and Cyp1B1. In addition we validated increase for four genes by SWCNT, namely ATM, CCNC, DNAJB4, and GADD45A by RT-PCR. Moreover results of the altered stress related genes have been discussed and that partially explains some of the toxic responses induced by single-walled carbon nanotubes.