bluuebunny/crossref_metadata_2025 huggingface dataset:
Ischemic preconditioning protects by activating prosurvival kinases at reperfusion
Authors: Hausenloy Derek J. , Tsang A. , Mocanu Mihaela M. , Yellon Derek M.
Published: September 2004

Pharmacological activation of the prosurvival kinases Akt and ERK-1/2 at reperfusion, after a period of lethal ischemia, protects the heart against ischemia-reperfusion injury. We hypothesized that ischemic preconditioning (IPC) protects the heart by phosphorylating the prosurvival kinases Akt and ERK-1/2 at reperfusion. In isolated perfused Sprague-Dawley rat hearts subjected to 35 min of lethal ischemia, the phosphorylation states of Akt, ERK-1/2, and p70 S6 kinase (p70S6K) were determined after 15 min of reperfusion, and infarct size was measured after 120 min of reperfusion. IPC induced a biphasic response in Akt and ERK-1/2 phosphorylation during the preconditioning and reperfusion phases after the period of lethal ischemia. IPC induced a fourfold increase in Akt, ERK-1/2, and p70S6K phosphorylation at reperfusion and reduced the infarct risk-to-volume ratio (56.9 ± 5.7 and 20.9 ± 3.6% for control and IPC, respectively, P < 0.01). Inhibiting the IPC-induced phosphorylation of Akt, ERK-1/2, and p70S6K at reperfusion with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002 or the MEK-1/2 inhibitor PD-98059 abrogated IPC-induced protection (46.3 ± 5.8, 49.2 ± 4.0, and 20.9 ± 3.6% for IPC + LY-294002, IPC + PD-98059, and IPC, respectively, P < 0.01), demonstrating that the phosphorylation of these kinases at reperfusion is required for IPC-induced protection. In conclusion, we demonstrate that the reperfusion phase following sustained ischemia plays an essential role in mediating IPC-induced protection. Specifically, we demonstrate that IPC protects the heart by phosphorylating the prosurvival kinases Akt and ERK-1/2 at reperfusion.
Regulation of the membrane-localized prostaglandin E synthases mPGES-1 and mPGES-2 in cardiac myocytes and fibroblasts
Authors: Giannico Giovanna , Mendez Mariela , LaPointe Margot C.
Published: September 2004

The proinflammatory mediator cyclooxygenase (COX)-2 and its product PGE2 are induced in the ischemic heart, contributing to inflammatory cell infiltration, fibroblast proliferation, and cardiac hypertrophy. PGE2 synthesis coupled to COX-2 involves two membrane-localized PGE synthases, mPGES-1 and mPGES-2; however, it is not clear how these synthases are regulated in cardiac myocytes and fibroblasts. To study this, we used primary cultures of neonatal ventricular myocytes (VM) and fibroblasts (VF) treated with IL-1β for 24 h. To test for involvement of MAPKs in IL-1β regulation of mPGES-1 and-2, cells were pretreated with the pharmacological inhibitors of p42/44 MAPK, p38 MAPK, and c-Jun kinase (JNK). mRNA was analyzed by RT-PCR. Protein was analyzed by densitometry of Western blots. mPGES-1 was undetectable in untreated VF but induced by IL-1β; inhibition of either p42/44 MAPK or JNK, but not p38 MAPK, was almost completely inhibitory. In VM, inhibition of the three MAPKs reduced IL-1β-stimulated mPGES-1 protein by 70–90%. mPGES-2 was constitutively synthesized in both VM and VF and was not regulated by IL-1β or MAPKs. Confocal microscopy revealed colocalization of both mPGES-1 and mPGES-2 with COX-2 in the perinuclear area of both VF and VM. Finally, PGE2 production was higher in VM than VF. Our data show that 1) mPGES-1 is induced in both VF and VM, 2) regulation of mPGES-1 by MAPK family members is different in the two cell types, 3) mPGES-2 is constitutively synthesized in both VM and VF and is not regulated, and 4) mPGES-1 and mPGES-2 are colocalized with COX-2 in both cells. Thus differences in activity of mPGES-1 and COX-2 or coupling of COX-2 with mPGES-1 may contribute to differences in PGE2 production by myocytes and fibroblasts.
Increased oral and decreased intestinal sensitivity to sucrose in obese, prediabetic CCK-A receptor-deficient OLETF rats
Authors: De Jonghe Bart C. , Hajnal Andras , Covasa Mihai
Published: September 2004

CCK-A receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rats are hyperphagic and develop obesity and Type 2 diabetes. In this strain, taste preference functions have not been investigated. Therefore, a series of short-access, two-bottle tests were performed in age-matched prediabetic OLETF and nonmutant Long-Evans Tokushima Otsuka (LETO) rats to investigate preference for sucrose (0.03, 0.1, 0.3, or 1.0 M) presented with a choice of water. To discern orosensory from postgastric factors that may contribute to this preference, in a separate experiment, rats were allowed to sham feed sucrose in the absence or presence of duodenal sucrose infusion (0.3, 0.6, or 1.0 M). In the two-bottle real-feeding tests, OLETF rats exhibited a greater preference for 0.3 M sucrose (91.2 ± 1.7 and 78.5 ± 3.4% for OLETF and LETO, respectively; P < 0.01) and 1.0 M sucrose (65.3 ± 1.2 and 57.5 ± 2.7% for OLETF and LETO, respectively; P < 0.05) than LETO rats. OLETF rats also sham fed less of the lowest (0.03 M; 33.8 ± 4.8 and 58.3 ± 7.3 ml for OLETF and LETO, respectively; P < 0.05) and more of the highest (1.0 M; 109.9 ± 6.5 and 81.0 ± 3.9 ml for OLETF and LETO, respectively; P < 0.01) concentration of sucrose relative to LETO rats. Finally, intraduodenal sucrose infusions (0.6 and 1.0 M) produced a smaller reduction of 0.3 M sham sucrose intake [14.1 ± 8.1 vs. 52.5 ± 3.3 ml and 49.4 ± 8.0 vs. 82.4 ± 3.2 ml for 0.6 M ( P < 0.01) and 1.0 M ( P < 0.05) infusions in OLETF and LETO, respectively]. These findings demonstrate that OLETF rats display an increased preference for sucrose, an effect that is at least partially influenced by the orosensory stimulating effect of sucrose. This enhanced responsiveness to oral stimulation, coupled with the deficit in responding to the postingestive feedback of intestinal sucrose, may contribute additively to the development of hyperphagia and weight gain in OLETF rats.
Doxycycline effects on mechanical and morphometrical properties of early- and late-stage osteoarthritic bone following anterior cruciate ligament injury
Authors: Pardy Connor K. , Matyas John R. , Zernicke Ronald F.
Published: September 2004

As posttraumatic osteoarthritis (OA) progresses, the mechanical and morphometrical properties of the subchondral bone change and may be linked to damage of the articular cartilage. Potentially to slow that progression, doxycycline was administered orally twice daily (4 mg·kg−1·day−1) in skeletally mature canines after anterior cruciate ligament transection (ACLX). To test if doxycycline significantly altered the structure and function of OA bone, we tested cancellous bone mechanical properties, measured bone mineral content, and analyzed bone structure by microcomputed tomography. Our investigation focused on subchondral trabecular bone changes in the medial femoral condyle at 36 and 72 wk after ACLX. Significant mechanical changes discovered at 36 wk post-ACLX were less obvious at 72 wk in both treated and ACLX groups. Doxycycline treatment conserved bone strain energy density at 72 wk. Doxycycline had little effect on the degradation of superficial osseous tissue at 36 wk post-ACLX; by 72 wk, doxycycline in an ACLX model limited subchondral bone loss within the first 3 mm of periarticular bone with established OA. Significant bone loss occurred in the deeper trabecular bone for all groups. Substantial architectural adaptation within deeper trabecular bone accompanied changes in mechanics in early and established OA.
Lactate dehydrogenase expression at the onset of altered loading in rat soleus muscle
Authors: Washington Tyrone A. , Reecy James M. , Thompson Raymond W. , Lowe Larry L. , McClung Joseph M. , Carson James A.
Published: September 2004

Both functional overload and hindlimb disuse induce significant energy-dependent remodeling of skeletal muscle. Lactate dehydrogenase (LDH), an important enzyme involved in anaerobic glycolysis, catalyzes the interconversion of lactate and pyruvate critical for meeting rapid high-energy demands. The purpose of this study was to determine rat soleus LDH-A and -B isoform expression, mRNA abundance, and enzymatic activity at the onset of increased or decreased loading in the rat soleus muscle. The soleus muscles from male Sprague-Dawley rats were functionally overloaded for up to 3 days by a modified synergist ablation or subjected to disuse by hindlimb suspension for 3 days. LDH mRNA concentration was determined by Northern blotting, LDH protein isoenzyme composition was determined by zymogram analysis, and LDH enzymatic activity was determined spectrophotometrically. LDH-A mRNA abundance increased by 372%, and LDH-B mRNA abundance decreased by 43 and 31% after 24 h and 3 days of functional overload, respectively, compared with that in control rats. LDH protein expression demonstrated a shift by decreasing LDH-B isoforms and increasing LDH-A isoforms. LDH-B activity decreased 80% after 3 days of functional overload. Additionally, LDH-A activity increased by 234% following 3 days of hindlimb suspension. However, neither LDH-A or LDH-B mRNA abundance was affected following 3 days of hindlimb suspension. In summary, the onset of altered loading induced a differential expression of LDH-A and -B in the rat soleus muscle, favoring rapid energy production. Long-term altered loading is associated with myofiber conversion; however, the rapid changes in LDH at the onset of altered loading may be involved in other physiological processes.
Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons
Authors: Kc Prabha , Mayer Catherine A. , Haxhiu Musa A.
Published: September 2004

In ferrets, we investigated the presence of choline acetyltransferase (ChAT), vasoactive intestinal peptide (VIP), and markers for nitric oxide synthase (NOS) in preganglionic parasympathetic neurons innervating extrathoracic trachea and intrapulmonary airways. Cholera toxin β-subunit, a retrograde axonal transganglionic tracer, was used to identify airway-related vagal preganglionic neurons. Double-labeling immunohistochemistry and confocal microscopy were employed to characterize the chemical nature of identified airway-related vagal preganglionic neurons at a single cell level. Physiological experiments were performed to determine whether activation of the VIP and ChAT coexpressing vagal preganglionic neurons plays a role in relaxation of precontracted airway smooth muscle tone after muscarinic receptor blockade. The results showed that 1) all identified vagal preganglionic neurons innervating extrathoracic and intrapulmonary airways are acetylcholine-producing cells, 2) cholinergic neurons innervating the airways coexpress ChAT and VIP but do not contain NOS, and 3) chemical stimulation of the rostral nucleus ambiguus had no significant effect on precontracted airway smooth muscle tone after muscarinic receptor blockade. These studies indicate that vagal preganglionic neurons are cholinergic in nature and coexpress VIP but do not contain NOS; their stimulation increases cholinergic outflow, without activation of inhibitory nonadrenergic, noncholinergic ganglionic neurons, stimulation of which induces airway smooth muscle relaxation. Furthermore, these studies do not support the possibility of direct inhibitory innervation of airway smooth muscle by vagal preganglionic fibers that contain VIP.
Alveolus formation: what have we learned from genetic studies?
Authors: Yan Cong , Du Hong
Published: September 2004

The respiratory system has two basic functions: air exchange and pathogen clearance. The conducting airway and alveolar parenchyma are the basic structures to fulfill these functions during respiratory cycles. In humans, there are ∼40 cell types in the lung that coordinately work together through various structural and signaling molecules. These molecules are vital for maintaining normal lung functions in response to environmental changes. Aberrant expression of these molecules can jeopardize human health and cause various pulmonary diseases. In this article, we will review some recent progress made in the pulmonary field, using genetic animal model systems to elucidate molecular mechanisms that are important for alveolar formation and lung diseases.
Branched-chain amino acid supplementation and human performance when hypohydrated in the heat
Authors: Cheuvront Samuel N. , Carter Robert , Kolka Margaret A. , Lieberman Harris R. , Kellogg Mark D. , Sawka Michael N.
Published: September 2004

The serotonin system may contribute to reduced human performance when hypohydrated in the heat. This study determined whether branched-chain amino acid (BCAA) supplementation could sustain exercise and cognitive performance in the heat (40°C dry bulb, 20% relative humidity) when hypohydrated by 4% of body mass. Seven heat-acclimated men completed two experimental trials, each consisting of one preparation and one test day. On day 1, a low-carbohydrate diet was eaten and subjects performed exhaustive cycling (morning) and treadmill exercise in the heat (afternoon) to lower muscle glycogen and achieve the desired hypohydration level. On day 2, subjects consumed an isocaloric BCAA and carbohydrate (BC) or carbohydrate-only drink during exercise. Experimental trials included 60 min of cycle ergometry (50% peak oxygen uptake) followed by a 30-min time trial in the heat. A cognitive test battery was completed before and after exercise, and blood samples were taken. BC produced a 2.5-fold increase ( P < 0.05) in plasma BCAA and lowered ( P < 0.05) the ratios of total tryptophan to BCAA and large neutral amino acid. Blood prolactin, glucose, lactate, and osmolality were not different between trials but increased over time. Cardiovascular and thermoregulatory data were also similar between trials. BC did not alter time-trial performance, cognitive performance, mood, perceived exertion, or perceived thermal comfort. We conclude that BCAA does not alter exercise or cognitive performance in the heat when subjects are hypohydrated.
Use of intramuscular triacylglycerol as a substrate source during exercise in humans
Authors: van Loon Luc J. C.
Published: September 2004

Fat and carbohydrate are the principal substrates that fuel aerobic ATP synthesis in skeletal muscle. Most endogenous fat is stored as triacylglycerol in subcutaneous and deep visceral adipose tissue. Smaller quantities of triacylglycerol are deposited as lipid droplets inside skeletal muscle fibers. The potential role of intramyocellular triacylglycerol (IMTG) as a substrate source during exercise in humans has recently regained much of its interest because of the proposed functional relationship between IMTG accumulation and the development of skeletal muscle insulin resistance. Exercise likely represents an effective means to prevent excess IMTG accretion by stimulating its rate of oxidation. However, there is much controversy on the actual contribution of the IMTG pool as a substrate source during exercise. The apparent discrepancy in the literature likely stems from methodological difficulties that have been associated with the methods used to estimate IMTG oxidation during exercise. However, recent studies using stable isotope methodology,1H-magnetic resonance spectroscopy, and electron and/or immunofluorescence microscopy all support the contention that the IMTG pool can function as an important substrate source during exercise. Although more research is warranted, IMTG mobilization and/or oxidation during exercise seem to be largely determined by exercise intensity, exercise duration, macronutrient composition of the diet, training status, gender, and/or age. In addition, indirect evidence suggests that the capacity to mobilize and/or oxidize IMTG is substantially impaired in an obese and/or Type 2 diabetic state. As we now become aware that skeletal muscle has an enormous capacity to oxidize IMTG stores during exercise, more research is warranted to develop combined exercise, nutritional, and/or pharmacological interventions to effectively stimulate IMTG oxidation in sedentary, obese, and/or Type 2 diabetes patients.
Cannabinoid receptor expression in peripheral arterial chemoreceptors during postnatal development
Authors: McLemore Gabrielle L. , Cooper Reed Z. B. , Richardson Kimberlei A. , Mason Ariel V. , Marshall Cathleen , Northington Frances J. , Gauda Estelle B.
Published: September 2004

Prenatal exposure to tobacco smoke increases risk of sudden infant death syndrome (SIDS). Marijuana is frequently smoked in conjunction with tobacco, and perinatal exposure to marijuana is associated with increased incidence of SIDS. Abnormalities in peripheral arterial chemoreceptor responses during sleep may be operative in infants at risk for SIDS, and nicotine exposure adversely affects peripheral arterial chemoreceptor responses. To determine whether marijuana could potentially affect the activity of peripheral arterial chemoreceptors during early postnatal development, we used in situ hybridization histochemistry to characterize the pattern and level of mRNA expression for cannabinoid type 1 receptor (CB1R) in the carotid body, superior cervical ganglia (SCG), and nodose-petrosal-jugular ganglia (NG-PG-JG) complex in newborn rats. We used immunohistochemistry and light, confocal, and electron microscopy to characterize the pattern of CB1R and tyrosine hydroxylase protein expression. CB1R mRNA expression was intense in the NG-PG-JG complex, low to moderate in the SCG, and sparse in the carotid body. With maturation, CB1R gene expression significantly increased ( P < 0.01) in the NG-PG-JG complex. CB1R immunoreactivity was localized to nuclei of ganglion cells in the SCG and NG-PG-JG complex, whereas tyrosine hydroxylase immunoreactivity was localized to the cytoplasm. Exposure to marijuana during early development could potentially modify cardiorespiratory responses via peripheral arterial chemoreceptors. The novel finding of nuclear localization of CB1Rs in peripheral ganglion cells suggests that these receptors may have an, as yet, undetermined role in nuclear signaling in sensory and autonomic neurons.
Apoptosis in lung injury and remodeling
Authors: Li Xiaopeng , Shu Ruijie , Filippatos Gerasimos , Uhal Bruce D.
Published: September 2004

The mode of cell death termed apoptosis, sometimes referred to as programmed cell death, is as critical a determinant of cell population size as is cell proliferation. Although best characterized in cells of the immune system, apoptosis is now known to be a key factor in the maintenance of normal cell turnover within structural cells in the parenchyma of virtually every organ. Recent interest in apoptosis in the lung has sparked a surge of investigations designed to determine the roles of apoptosis in lung development, injury, and remodeling. Of particular recent interest are the roles of apoptosis in disease pathogenesis and resolution, in which the concept of apoptosis as a “programmed” cell death, i.e., genetically determined, is often more accurately viewed as “inappropriate cell suicide” with regard to its extent and/or timing. Data accumulating over the past decade have made clear the complexity of the control of lung cell apoptosis; concepts of the regulation of apoptosis originally determined in classical cell culture models are often, but not always, applicable to structural cells. For this reason, each of the many cell types of the lung must be studied as a potentially new subject with its own idiosyncrasies yet to be discovered. In light of the large volume of literature now available, this article focuses on the roles of apoptosis in three pathophysiological contexts: acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis. Each section presents key data describing the evidence for apoptosis in the lung, its possible relevance to disease pathogenesis, and proposed mechanisms that might suggest potential avenues for therapeutic intervention.
Lung volumes and alveolar expansion pattern in immature rabbits treated with serum-diluted surfactant
Authors: Xu Yongmei , Kobayashi Tsutomu , Cui Xiaoguang , Ohta Keisuke , Kabata Chiharu , Tashiro Katsumi
Published: September 2004

In acute respiratory distress syndrome, mechanical ventilation often induces alveolar overdistension aggravating the primary insult. To examine the mechanism of overdistension, surfactant-deficient immature rabbits were anesthetized with pentobarbital sodium, and their lungs were treated with serum-diluted modified natural surfactant (porcine lung extract; 2 mg/ml, 10 ml/kg). By mechanical ventilation with a peak inspiration pressure of 22.5 cmH2O, the animals had a tidal volume of 14.7 ml/kg (mean), when 2.5 cmH2O positive end-expiratory pressure was added. This volume was similar to that in animals treated with nondiluted modified natural surfactant (24 mg/ml in Ringer solution, 10 ml/kg). However, the lungs fixed at 10 cmH2O on the deflation limbs of the pressure-volume curve had the largest alveolar/alveolar duct profiles (≥48,000 μm2), accounting for 38% of the terminal air spaces, and the smallest (<6,000 μm2), accounting for 31%. These values were higher than those in animals treated with nondiluted modified natural surfactant ( P < 0.05). We conclude that administration of serum-diluted surfactant to immature neonatal lungs leads to patchy overdistension of terminal air spaces, similar to the expansion pattern that may be seen after dilution of endogenous surfactant with proteinaceous edema fluid in acute respiratory distress syndrome.
Contribution of Afferent Feedback to the Soleus Muscle Activity During Human Locomotion
Authors: Mazzaro Nazarena , Grey Michael J. , Sinkjær Thomas
Published: September 2004

During the stance phase of the human step cycle, the ankle undergoes a natural dorsiflexion that stretches the soleus muscle. The afferent feedback resulting from this stretch enhances the locomotor drive. In this study a robotic actuator was used to slightly enhance or reduce the natural ankle dorsiflexion, in essence, mimicking the small variations in the ankle dorsiflexion movement that take place during the stance phase of the step cycle. The soleus (SOL) and tibialis anterior EMG were analyzed in response to the ankle trajectory modifications. The dorsiflexion enhancements and reductions generated gradual increments and decrements, respectively, in the ongoing SOL EMG. We exercised care to ensure that the imposed ankle movements were too slow to elicit distinct burst-like stretch reflex responses that have been investigated previously. The increased SOL EMG after the dorsiflexion enhancements was reduced when the group Ia afferents were blocked with peripheral ischemia at the thigh, and during high-frequency Achilles tendon vibration. However, neither ischemia nor tendon vibration affected the decrements in the SOL EMG during the dorsiflexion reductions. These findings give evidence of the contribution of afferent feedback to the SOL activity in an ongoing basis during the stance phase. The results suggest that mainly feedback from the group Ia pathways is responsible for the increments in the SOL EMG during the dorsiflexion enhancements. However, the decrements in the SOL activity might be mediated by different afferent mechanisms.
Regulation of Synaptic Inputs to Paraventricular-Spinal Output Neurons by α2 Adrenergic Receptors
Authors: Li De-Pei , Atnip Lindsay M. , Chen Shao-Rui , Pan Hui-Lin
Published: September 2004

Neurons in the paraventricular nucleus (PVN) that project to the brain stem and spinal cord are important for autonomic regulation. The excitability of preautonomic PVN neurons is controlled by the noradrenergic input from the brain stem. In this study, we determined the role of α2 adrenergic receptors in the regulation of excitatory and inhibitory synaptic inputs to spinally projecting PVN neurons. Excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) were recorded using whole cell voltage-clamp techniques on PVN neurons labeled by a retrograde fluorescence tracer injected into the thoracic spinal cord of rats. Bath application of 5–20 μM clonidine, an α2 receptor agonist, significantly reduced the amplitude of evoked GABAergic IPSCs in a dose-dependent manner. Also, 10 μM clonidine significantly decreased the frequency (from 2.68 ± 0.41 to 1.22 ± 0.40 Hz) but not the amplitude of miniature IPSCs (mIPSCs), and this effect was blocked by the α2 receptor antagonist yohimbine. Furthermore, clonidine increased the paired-pulse ratio of evoked IPSCs from 1.25 ± 0.05 to 1.61 ± 0.08 ( P < 0.05). On the other hand, clonidine had little effect on evoked glutamatergic EPSCs, mEPSCs, and the paired-pulse ratio of evoked EPSCs in most labeled cells examined. Additionally, immunofluorescence labeling revealed that the α2A receptor and GABA immunoreactivities were co-localized in close apposition to labeled PVN neurons. Collectively, these data suggest that stimulation of α2 adrenergic receptors primarily attenuates GABAergic inputs to PVN output neurons to the spinal cord. The presynaptic α2 receptors function as heteroreceptors to modulate synaptic GABA release and contribute to the hypothalamic regulation of sympathetic outflow.
Contralateral White Noise Selectively Changes Right Human Auditory Cortex Activity Caused by a FM-Direction Task
Authors: Behne Nicole , Scheich Henning , Brechmann André
Published: September 2004

Animal and human studies suggest that directional categorization of frequency-modulated (FM) tones (rising vs. falling) is a function of the right auditory cortex (AC). To investigate this hemispheric specialization in more detail, we analyzed both the binaural and monaural representation of FM tones and the influence of contralateral white noise on the processing of FM tone direction. In two fMRI-experiments, FM tones with varied direction, center-frequencies, and duration were presented binaurally or monaurally without contralateral white noise (experiment 1) and with contralateral white noise (experiment 2) while the subjects had to perform the same directional categorization task. In experiment 1, contralateral FM tones led to strongest activation, binaural FM tones to intermediate, and ipsilateral FM tones to weakest activation in each AC. This is in accordance with binaural response properties of neurons in animal AC. In experiment 2, contralateral white noise had no significant effect on the activation of left AC by FM tones, whereas in right AC, it led to a significant increase in activation for ipsilateral FM tones. This result provides further support for the critical role of right AC for directional categorization of FM tones, which for ipsilateral input has to be processed in competition to the excitatory input of white noise via the direct contralateral pathway.
Synaptic Depression in Conjunction With A-Current Channels Promote Phase Constancy in a Rhythmic Network
Authors: Greenberg Idan , Manor Yair
Published: September 2004

In many central pattern generators, pairs of neurons maintain an approximately fixed phase despite large changes in the frequency. The mechanisms underlying phase maintenance are not clear. Previous theoretical work suggested that inhibitory synapses that show short-term depression could play a critical role in this respect. In this work we examine how the interaction between synaptic depression and the kinetics of a transient potassium (A-like) current could be advantageous for phase constancy in a rhythmic network. To demonstrate the mechanism in the context of a realistic central pattern generator, we constructed a detailed model of the crustacean pyloric circuit. The frequency of the rhythm was modified by changing the level of a ligand-activated current in one of the pyloric neurons. We examined how the time difference of firing activities between two selected neurons in this circuit is affected by synaptic depression, A-current, and a combination of the two. We tuned the parameters of the model such that with synaptic depression alone, or A-current alone, phase was not maintained between these two neurons. However, when these two components came together, they acted synergistically to maintain the phase across a wide range of cycle periods. This suggests that synaptic depression may be necessary to allow an A-current to delay a postsynaptic neuron in a frequency-dependent manner, such that phase invariance is ensured.
Cerebellar Involvement in Anticipating the Consequences of Self-Produced Actions During Bimanual Movements
Authors: Diedrichsen Jörn , Verstynen Timothy , Lehman Steven L. , Ivry Richard B.
Published: September 2004

Anticipatory postural adjustments (APA) during bimanual actions can be observed when participants hold an object in one hand and then lift it with the other hand. The postural force used to hold the object is reduced in anticipation of unloading, indicating an accurate prediction of the change in load. We examined patients with unilateral or bilateral cerebellar damage as well as two individuals lacking the corpus callosum on the bimanual unloading task. The acallosal patients showed an intact APA, suggesting subcortical integration of motor signals for anticipatory adjustments during bimanual actions. Contrary to the hypothesis that the cerebellum is critical for predicting and compensating for the consequences of our actions, we found that the well-learned APA in this task was largely intact in cerebellar patients. However, cerebellar damage abolished short-term adaptation of the APA, and the patients were unable to acquire an APA in a similar but previously untrained situation. These results indicate that while over-learned anticipatory adjustments are preserved after cerebellar lesions, adaptation of this response and the acquisition of a novel coordination requires the cerebellum ipsilateral to the postural hand. Furthermore, this structure appears to be essential for the accurate timing of previously learned behaviors. The patients with cerebellar damage showed poorly timed adjustments with the APA beginning earlier than in healthy participants.
A Point Process Framework for Relating Neural Spiking Activity to Spiking History, Neural Ensemble, and Extrinsic Covariate Effects
Authors: Truccolo Wilson , Eden Uri T. , Fellows Matthew R. , Donoghue John P. , Brown Emery N.
Published: September 2004

Multiple factors simultaneously affect the spiking activity of individual neurons. Determining the effects and relative importance of these factors is a challenging problem in neurophysiology. We propose a statistical framework based on the point process likelihood function to relate a neuron's spiking probability to three typical covariates: the neuron's own spiking history, concurrent ensemble activity, and extrinsic covariates such as stimuli or behavior. The framework uses parametric models of the conditional intensity function to define a neuron's spiking probability in terms of the covariates. The discrete time likelihood function for point processes is used to carry out model fitting and model analysis. We show that, by modeling the logarithm of the conditional intensity function as a linear combination of functions of the covariates, the discrete time point process likelihood function is readily analyzed in the generalized linear model (GLM) framework. We illustrate our approach for both GLM and non-GLM likelihood functions using simulated data and multivariate single-unit activity data simultaneously recorded from the motor cortex of a monkey performing a visuomotor pursuit-tracking task. The point process framework provides a flexible, computationally efficient approach for maximum likelihood estimation, goodness-of-fit assessment, residual analysis, model selection, and neural decoding. The framework thus allows for the formulation and analysis of point process models of neural spiking activity that readily capture the simultaneous effects of multiple covariates and enables the assessment of their relative importance.
Integration of Target and Effector Information in Human Posterior Parietal Cortex for the Planning of Action
Authors: Medendorp W. Pieter , Goltz Herbert C. , Crawford J. Douglas , Vilis Tutis
Published: September 2004

Recently, using event-related functional MRI (fMRI), we located a bilateral region in the human posterior parietal cortex (retIPS) that topographically represents and updates targets for saccades and pointing movements in eye-centered coordinates. To generate movements, this spatial information must be integrated with the selected effector. We now tested whether the activation in retIPS is dependent on the hand selected. Using 4-T fMRI, we compared the activation produced by movements, using either eyes or the left or right hand, to targets presented either leftward or rightward of central fixation. The majority of the regions activated during saccades were also activated during pointing movements, including occipital, posterior parietal, and premotor cortex. The topographic retIPS region was activated more strongly for saccades than for pointing. The activation associated with pointing was significantly greater when pointing with the unseen hand to targets ipsilateral to the hand. For example, although there was activation in the left retIPS when pointing to targets on the right with the left hand, the activation was significantly greater when using the right hand. The mirror symmetric effect was observed in the right retIPS. Similar hand preferences were observed in a nearby anterior occipital region. This effector specificity is consistent with previous clinical and behavioral studies showing that each hand is more effective in directing movements to targets in ipsilateral visual space. We conclude that not only do these regions code target location, but they also appear to integrate target selection with effector selection.
Sufficient and necessary condition for the permanence of periodic predator‐prey system
Authors: Cui Jingan , Song Xinyu
Published: September 2004

We consider the permanence of a periodic predator‐prey system, where the prey disperse in a two‐patch environment. We assume the Volterra within‐patch dynamics and provide a sufficient and necessary condition to guarantee the predator and prey species to be permanent by using the techniques of inequality analysis. Our work improves previous relevant results.
On the classification of the Lie algebras Lr,ts
Authors: Hanna L. A-M.
Published: September 2004

The Lie algebras introduced by the author (2003) are classified from an algebraic point of view. A matrix representation of least degree is given for each isomorphism class.
I‐Lindelof spaces
Authors: Al-Zoubi Khalid , Al-Nashef Bassam
Published: September 2004

We define a space (X, T) to be I‐Lindelof if every cover 𝒜 of X by regular closedsubsetsof the space (X, T) contains a countable subfamily 𝒜′ suchthat X = ∪{int(A) : A ∈ A′}. We provide several characterizations of I‐Lindelofspaces and relate them to some other previously known classes of spaces, for example, rc‐Lindelof, nearly Lindelof, and so forth. Our study here of I‐Lindelofspaces also deals with operations on I‐Lindelof spaces and, in its last part, investigates images and inverseimagesof I‐Lindelofspacesundersome consideredtypesof functions.
The fluid profile during spin‐coating over a small sinusoidal topography
Authors: Hayes M. A. , O′Brien S. B. G.
Published: September 2004

We consider spin‐coating over a small sinusoidal topography modelling the physical problem of the coating of a television screen. This involves depositing a phosphor layer on a substrate with a precoating consisting of small parallel striations. Despite the fact that the basic flow is radial, we show that the final liquid coating does not have radial variation; rather, it varies according to the underlying topography. We use a thin film model resulting in an evolution equation for the fluid thickness and sketch several techniques for obtaining approximate solutions in appropriate limiting situations.
Making nontrivially associated modular categories from finite groups
Authors: Al-Shomrani M. M. , Beggs E. J.
Published: September 2004

We show that the double 𝒟 of the nontrivially associated tensor category constructed from left coset representatives of a subgroup of a finite group X is a modular category. Also we give a definition of the character of an object in this category as an element of a braided Hopf algebra in the category. This definition is shown to be adjoint invariant and multiplicative on tensor products. A detailed example is given. Finally, we show an equivalence of categories between the nontrivially associated double 𝒟 and the trivially associated category of representations of the Drinfeld double of the group D(X).
On differential subordinations for a class of analytic functions defined by a linear operator
Authors: Ravichandran V. , Silverman Herb , Kumar S. Sivaprasad , Subramanian K. G.
Published: September 2004

We obtain several results concerning the differential subordination between analytic functions and a linear operator defined for a certain family of analytic functions which are introduced here by means of these linear operators. Also, some special cases are considered.
Operators commuting with the shift on sequence spaces
Authors: Prada J.
Published: September 2004

A complete characterization of shift‐invariant operators that are isomorphisms is given in certain sequence spaces. Also given is a sufficient condition for an operator commuting with a shift‐invariant operator to be shift invariant.
On the ranges of discrete exponentials
Authors: Caragiu Florin , Caragiu Mihai
Published: September 2004

Let a > 1 be a fixed integer. We prove that there is no first‐order formula ϕ(X) in one free variable X, written in the language of rings, such that for any prime p with gcd(a, p) = 1 the set of all elements in the finite prime field Fp satisfying ϕ coincides with the range of the discrete exponential function t ↦ at(modp).
A remark on a complementarity problem in Banach space
Authors: Nanda Sudarsan
Published: September 2004

We give a modified proof of the theorem given in an earlier paper of the author (1994).
On existence of extremal solutions of nonlinear functional integral equations in Banach algebras
Authors: Dhage B. C.
Published: September 2004

An algebraic fixed point theorem involving the three operators in a Banach algebra is proved using the properties of cones and they are further applied to a certain nonlinear integral equations of mixed type for proving the existence of maximal and minimal solutions. Our results include the earlier fixed point theorems of Dhage (1992 and 1999) as special cases with a different but simple method.
The Pólya‐Aeppli process and ruin problems
Authors: Minkova Leda D.
Published: September 2004

The Pólya‐Aeppli process as a generalization of the homogeneous Poisson process is defined. We consider the risk model in which the counting process is the Pólya‐Aeppli process. It is called a Pólya‐Aeppli risk model. The problem of finding the ruin probability and the Cramér‐Lundberg approximation is studied. The Cramér condition and the Lundberg exponent are defined. Finally, the comparison between the Pélya‐Aeppli risk model and the corresponding classical risk model is given.
Recursive estimation of the claim rates and sizes in an insurance model
Authors: Aggoun Lakhdar
Published: September 2004

It is a common fact that for most classes of general insurance, many possible sources of heterogeneity of risk exist. Premium rates based on information from a heterogeneous portfolio might be quite inadequate. One way of reducing this danger is by grouping policies according to the different levels of the various risk factors involved. Using measure change techniques, we derive recursive filters and predictors for the claim rates and claim sizes for the different groups.
Existence, uniqueness, and regularity of solutions to semilinear retarded differential equations
Authors: Bahuguna D.
Published: September 2004

In the present work, we consider a semilinear retarded differential equation in a Banach space. We first establish the existence and uniqueness of a mild solution and then prove its regularity under different additional conditions. Finally, we consider some applications of the abstract results.
Hemiequilibrium problems
Authors: Noor Muhammad Aslam
Published: September 2004

We consider a new class of equilibrium problems, known as hemiequilibrium problems. Using the auxiliary principle technique, we suggest and analyze a class of iterative algorithms for solving hemiequilibrium problems, the convergence of which requires either pseudomonotonicity or partially relaxed strong monotonicity. As a special case, we obtain a new method for hemivariational inequalities. Since hemiequilibrium problems include hemivariational inequalities and equilibrium problems as special cases, the results proved in this paper still hold for these problems.
The fundamental solutions for fractional evolution equations of parabolic type
Authors: El-Borai Mahmoud M.
Published: September 2004

The fundamental solutions for linear fractional evolution equations are obtained. The coefficients of these equations are a family of linear closed operators in the Banach space. Also, the continuous dependence of solutions on the initial conditions is studied. A mixed problem of general parabolic partial differential equations with fractional order is given as an application.
A singular initial value problem for some functional differential equations
Authors: Agarwal Ravi P. , O′Regan Donal , Zernov Oleksandr E.
Published: September 2004

For the initial value problem trx′(t) = at + b1x(t) + b2x(q1t) + b3trx′(q2t) + φ(t, x(t), x(q1t), x′(t), x′(q2t)), x(0) = 0, where r > 1, 0 < qi ≤ 1, i ∈ {1, 2}, we find a nonempty set of continuously differentiable solutions x : (0, ρ] → ℝ, each of which possesses nice asymptotic properties when t → +0.
Effects of Deletion of the Tissue Inhibitor of Matrix Metalloproteinases-1 Gene on the Progression of Murine Thoracic Aortic Aneurysms
Authors: Ikonomidis John S. , Gibson William C. , Butler Jessica E. , McClister David M. , Sweterlitsch Sarah E. , Thompson Robert P. , Mukherjee Rupak , Spinale Francis G.
Published: September 2004

Objective—

The cause of thoracic aortic aneurysms (TAAs) is poorly understood. Previous work has suggested an association between development of aortic aneurysms and matrix metalloproteinase (MMP) activity. We hypothesized that removal of the primary endogenous aortic MMP inhibitor (TIMP) through TIMP-1 gene deletion will increase TAA progression.

Methods and Results—

The descending thoracic aortas of wild-type 129 SvE and TIMP-1 gene knockout (TIMP-1
−/−
) mice were exposed to 0.5 mol/L CaCl
2
for 15 minutes, with terminal studies performed at 4 or 8 weeks. TAA lumen diameter was measured using confocal microscopy and normalized to the ascending aorta. In addition, sections were studied with in situ zymography and immunohistochemistry staining for MMP-9. Both wild-type [TAA/ascending ratio (mean±SEM): control, 0.85±0.02 (n=14); 4 weeks, 1.00±0.03 (n=13); 8 weeks, 1.05±0.10 (n=9)] and TIMP-1
−/−
[control, 0.98±0.04 (n=11); 4 weeks, 1.10±0.03 (n =21); 8 weeks, 1.22±0.09 (n=10)] groups developed aneurysms at 4 and 8 weeks compared with their respective controls (
P
<0.05). TIMP-1
−/−
animals developed larger aneurysms than the corresponding wild-type group (
P
<0.05). Aneurysms in the TIMP-1
−/−
group were larger at 8 weeks than at 4 weeks (
P
<0.05), which was not seen in the wild-type aneurysm groups. Both groups showed presence of MMP-9 in 4 and 8 weeks, most prominently in the adventitia and outer media. In situ zymographic activity was increased in the 8-week TIMP-1
−/−
group compared with wild-type.

Conclusions—

Deletion of the TIMP-1 gene results in increased and continued progression of aneurysm formation compared with wild-type mice in a unique TAA model caused at least in part by an alteration in the balance between gelatinase activity and its endogenous inhibition. Therapeutic strategies aimed at modifying MMP activity may reduce or prevent the progression of TAAs.
Cytomegalovirus Infection in Heart Transplant Recipients Is Associated With Impaired Endothelial Function
Authors: Petrakopoulou Paraskevi , Kübrich Marion , Pehlivanli Sinan , Meiser Bruno , Reichart Bruno , von Scheidt Wolfgang , Weis Michael
Published: September 2004

Background—

Cardiac allograft vasculopathy (CAV) is initiated by allograft endothelial injury. We hypothesized that a major mechanism by which cytomegalovirus (CMV) could contribute to CAV is by dysregulation of the endothelial vasomotor response.

Methods—

Coronary endothelial vasomotor function was determined in 183 consecutive patients (24±33 months after transplantation), and was correlated with recipient and donor CMV serological status before transplantation and with documented CMV infection episodes (CMVpp65Ag+). Serial endothelial function measurements were performed in a subgroup of 53 transplant recipients (1 month and 12 months after transplantation). The composite endpoint of cardiovascular related events and death during a follow-up of 66±41 months was analyzed based on the CMV serological status before transplantation.

Results—

The medium event-free time for CMV-negative recipients of CMV-positive hearts was 8.1 years compared with 13.3 years for the other groups (
P
<0.05). Distal epicardial but not microvascular endothelial function was significantly impaired in CMV seronegative recipients of seropositive donor hearts (n=48) compared with all other groups (
P
<0.01 versus seronegative recipient/seronegative donor;
P
<0.05 versus seropositive recipient/seronegative donor;
P
<0.05 versus seropositive recipient/seropositive donor). Distal epicardial endothelial dysfunction was more pronounced in heart transplant recipients with a history of documented CMV infection compared with patients without any documented CMV infection (
P
<0.01). In a longitudinal subgroup analysis, distal epicardial and microcirculatory endothelial vasomotor response deteriorated significantly in recipients with documented CMV infection (
P
<0.05 versus baseline) but not in patients without previous CMV infection.

Conclusion—

Documented CMV infection episodes in heart transplant recipients are associated with impaired coronary endothelial function. CMV-negative recipients of CMV-positive donor hearts have an impaired distal epicardial endothelial function and an increased incidence of cardiovascular-related events and death during follow-up. CMV infection may contribute to allograft failure by accelerating coronary endothelial dysfunction.
Atrial Tachyarrhythmias After the Maze Procedure
Authors: Ishii Yosuke , Gleva Marye J. , Gamache M. Carolyn , Schuessler Richard B. , Boineau John P. , Bailey Marci S. , Damiano Ralph J.
Published: September 2004

Background—

The Maze procedure restores normal sinus rhythm in the majority of patients. However, atrial tachyarrhythmias (ATA) are a common early complication after the operation. The purpose of this study was to define the incidence and natural history of ATA after the Maze procedure.

Methods—

Complete medical records from 200 patients who underwent the Maze procedures (I, II, and III) from 1987 to 2002 were examined for all episodes of early postoperative ATA that occurred during the first 30 days after the procedure. Two electrophysiologists independently reviewed all postoperative 12-lead electrocardiograms.

Results—

ATA occurred in 86 patients (43%) after the Maze procedure. Of the patients with ATA, 59% had atrial fibrillation (AF), 14% had atrial flutter (AFL), and 27% had both AF and AFL. Of the patients with AF or AFL, 20% and 5%, respectively, also had episodes of atrial tachycardia and supraventricular tachyarrhythmia. The peak incidence of early postoperative ATA was on postoperative day 8. The average duration of ATA was 5.7±5.0 days. Late recurrence of AF (>1 year postoperatively) occurred in 7.0% of patients who had early postoperative ATA and 8.8% of patients without early postoperative ATA (
P
=0.8).

Conclusions—

ATA occurred in 43% of patients after the Maze procedure. The tachyarrhythmias occurred primarily within 8 days after surgery and resolved within 3 weeks in almost all patients. There was no relationship between the incidence of early postoperative ATA and the late recurrence of AF.