bluuebunny/crossref_metadata_2025 huggingface dataset:
Vesicular Trafficking of Semaphorin 3A is Activity‐Dependent and Differs Between Axons and Dendrites
Authors: de Wit Joris , Toonen Ruud F. , Verhaagen Joost , Verhage Matthijs
Published: May 2006

Secreted semaphorins act as guidance cues in the developing nervous system and may have additional functions in mature neurons. How semaphorins are transported and secreted by neurons is poorly understood. We find that endogenous semaphorin 3A (Sema3A) displays a punctate distribution in axons and dendrites of cultured cortical neurons. GFP–Sema3A shows a similar distribution and co‐localizes with secretory vesicle cargo proteins. Live‐cell imaging reveals highly dynamic trafficking of GFP–Sema3A vesicles with distinct properties in axons and dendrites regarding directionality, velocity, mobility and pausing time. In axons, most GFP–Sema3A vesicles move fast without interruption, almost exclusively in the anterograde direction, while in dendrites many GFP–Sema3A vesicles are stationary and move equally frequent in both directions. Disruption of microtubules, but not of actin filaments, significantly impairs GFP–Sema3A transport. Interestingly, depolarization induces a reversible arrest of axonal transport of GFP–Sema3A vesicles but has little effect on dendritic transport. Conversely, action potential blockade using tetrodotoxin (TTX) accelerates axonal transport, but not dendritic transport. These data indicate that axons and dendrites regulate trafficking of Sema3A and probably other secretory vesicles in distinct ways, with axons specializing in fast, uninterrupted, anterograde transport. Furthermore, neuronal activity regulates secretory vesicle trafficking in axons by a depolarization‐evoked trafficking arrest.
Association of Yeast Transporters with Detergent‐Resistant Membranes Correlates with Their Cell‐Surface Location
Authors: Lauwers Elsa , André Bruno
Published: May 2006

Detergent‐resistant membrane (DRM) fractions enriched in ergosterol and sphingolipids can be isolated from yeast cells and have been proposed to represent the biochemical equivalents of lipid rafts. Most yeast plasma membrane proteins studied for their detergent solubility have been found in DRMs, except for the Hxt1 and Gap1 permeases. We here compared Gap1 detergent solubility in wild‐type and various mutant cells under conditions promoting cell surface accumulation or ubiquitin‐dependent down‐regulation of the permease. We show that Gap1 present at the plasma membrane is associated with DRMs. This association occurs at the Golgi level. In the absence of sphingolipid neosynthesis, Gap1 fails to accumulate at the plasma membrane and is missorted to the vacuolar lumen. Furthermore, the presence of Gap1 at the plasma membrane correlates perfectly with its association with DRMs, whatever the activity or ubiquitination state of the permease and regardless of whether it has reached the cell surface via normal secretion, after recycling, or upon missorting to the vacuole before rerouting to the plasma membrane. Finally, we show that Hxt1 present at the cell surface is also associated with DRMs. We discuss a model where yeast plasma membrane proteins are systematically associated with sphingolipid/ergosterol‐enriched microdomains when located at the cell surface.
GABA‐site antagonism and pentobarbital actions do not depend on the α‐subunit type in the recombinant rat GABAA receptor
Authors: Rahman M. , Zhu D. , Lindblad C. , Johansson I.‐M. , Holmberg E. , Isaksson M. , Taube M. , Bäckström T. , Wang M.‐D.
Published: May 2006

Aim:  The roles of α‐subunits on the gamma‐aminobutyric acid (GABA)‐site antagonism and pentobarbital actions were examined in rat recombinant GABAA receptors in Xenopus oocytes.

Methods:  Experiments were performed with binary and ternary GABAA receptors containing α1‐, α4‐ or α5‐subunit by the two‐electrode voltage‐clamp technique.

Results:  The potency of GABA was significantly higher in the α1β2, α4β2 and α5β2 receptors compared with the α1β2γ2L, α4β2γ2L and α5β2γ2L receptors. However, the α5β2 receptor possessed significantly lower GABA efficacy compared with the α5β2γ2L receptor. While the γ2‐subunit was essential to the potency of GABA, its influence on the apparent GABA‐site antagonism was less profound. The antagonist affinity constants (KB) of bicuculline inhibition and slopes of Schild plots were similar between all types of ternary and binary receptors except α5β2 receptor which was not tested. The pKBs and IC50s of the GABA‐site antagonism were not significantly different between the α1β2γ2L, α4β2γ2L and α5β2γ2L receptors. Bicuculline blocked pentobarbital‐activated currents in a reversible and non‐competitive manner with the α1β2γ2L, α4β2γ2L, and α5β2γ2L receptors, indicating an allosteric inhibition of the GABA‐site. No significant difference of bicuculline potencies in inhibiting GABA‐ and pentobarbital‐activated currents was found between the α1β2γ2L, α4β2γ2L and α5β2γ2L receptors.

Conclusion:  The GABA‐site antagonism does not depend on the subtype of α‐subunits. Similarly, pentobarbital activates ternary receptors composed of different α‐subunits in a bicuculline‐sensitive manner. The potencies of bicuculline to inhibit pentobarbital‐activated currents are identical with receptors containing α1, α4 or α5‐subunit. The α1β2 and α4β2 receptors possess higher GABA potencies compared with the α1β2γ2L and α4β2γ2L receptors.
Time course of changes in angiogenesis‐related factors in denervated muscle
Authors: Wagatsuma A. , Osawa T.
Published: May 2006

Aim:  Denervation leads to capillary regression in skeletal muscle. To gain insight into the regulation of this process, we investigated the time course of changes in capillary supply and gene expression of angiogenesis‐related factors during muscle denervation.

Method:  Female mice underwent surgery to transect the sciatic nerve, and then the gastrocnemius muscles were isolated at 12 h, 1, 3, 5, 10, 20, or 30 days after surgery. The capillary supply was assessed by immunohistochemistry using anti‐PECAM‐1/CD31 antibody. The mRNA levels for angiogenesis‐related factors were analysed using a real‐time polymerase chain reaction.

Results:  We found that the capillary‐to‐fibre ratio began to decrease 10 days after muscle denervation and decreased by 52% after 30 days. The levels of mRNA for vascular endothelial growth factor (VEGF), its receptors [fms‐like tyrosine kinase (Flt‐1) and a kinase insert domain‐containing receptor/fetal liver kinase‐1 (KDR/Flk‐1)], angiopoietin‐1 and angiopoietin‐2 of denervated muscle were immediately down‐regulated after 12 h and remained lower than control muscle until 30 days after muscle denervation. The levels of mRNA for the VEGF receptor, neuropilin‐1, angiopoietin receptor and Tie‐2 decreased within 12–24 h, but returned to near those of control muscle after 10–20 days, and again decreased after 30 days.

Conclusions:  These findings suggest that denervation‐induced capillary regression may be associated with down‐regulation of VEGF and angiopoietin signalling.
BSAVA Manual of Canine and Feline Endocrinology
Authors: Scarff David H
Published: May 2006

BSAVA Manual of Canine and Feline Endocrinology
 Eds Carmel Mooney and Mark Peterson Published by BSAVA, 2004. Paperback, 240 pages Price £75.00. ISBN 0‐905214‐72‐2
Manual of Veterinary Dietetics
Authors: Elwood Clive
Published: May 2006

Manual of Veterinary Dietetics
 Tony Buffington, Cheryl Holloway, Sarah Abood Published by Elsevier, 2004. Paperback, 251 pages Price £29.99. ISBN 0‐7216‐0123‐5
Ultrasonographic diagnosis of unusual portal vascular abnormalities in two cats
Authors: McConnell J. F. , Sparkes A. H. , Ladlow J. , Doust R. , Davies S.
Published: May 2006

Two cases of ascites secondary to portal vascular abnormalities associated with portal hypertension are described. In the first case a five‐month‐old cat was presented with recurrent ascites and investigations showed that the underlying cause was a hepatic arteriovenous fistula. Ultrasonography showed direct communication of the coeliac artery and right branch of the portal vein. There was also hepatofugal flow in the main portal vein consistent with portal hypertension. The ultrasonographic features were similar to those seen in dogs with hepatic arteriovenous fistulae. In the second case, ascites, portal hypertension and an intraluminal mass in the main portal vein was diagnosed in a 16‐year‐old cat that had been presented with hyperthyroidism and hepatomegaly. Acquired portosystemic collaterals involving the left renal vein were present. Additional diagnostic investigations were not permitted. Ultrasonography was useful in both cases to document portal hypertension and the underlying cause.
Diagnosis of canine nasal aspergillosis by cytological examination: a comparison of four different collection techniques
Authors: De Lorenzi D. , Bonfanti U. , Masserdotti C. , Caldin M. , Furlanello T.
Published: May 2006

Objectives: To compare the efficacy and diagnostic value of four different sample collection techniques for cytological identification of nasal aspergillosis‐penicilliosis in dogs.

Methods: Fifteen dogs with a history of persistent nasal discharge and clinical and radiographic findings suggestive of aspergillosis were evaluated using four different cytological sampling techniques. These were a direct smear from the nasal discharge, blind swab collection under general anaesthesia, brushing from suspect lesions under direct endoscopic visualisation and a squash technique of mucosal biopsies from suspect lesions obtained under direct endoscopic visualisation.

Results: Direct smear collection and blind swab collection detected fungal hyphae in 13·3 and 20 per cent of examinaed cases, respectively; brush samples detected fungal hyphae in 93·3 per cent and fungal spores in the 45 per cent of examined cases and squash samples detected fungal hyphae in 100 per cent and fungal spores in 36 per cent of examined cases.

Clinical Significance: This study confirmed the high accuracy of cytology samples in the diagnosis of nasal aspergillosis‐penicilliosis when collected under direct endoscopic visualisation and showed the poor value of samples that were collected by blind swabs or prepared from samples of nasal discharge.
Surgical treatment of canine nasal aspergillosis by rhinotomy combined with enilconazole infusion and oral itraconazole
Authors: Claeys S. , Lefebvre J. ‐B. , Schuller S. , Hamaide A. , Clercx C.
Published: May 2006

Objectives:To evaluate the effectiveness of rhinotomy and surgical debridement associated with topical administration of 2 per cent enilconazole and oral itraconazole in dogs with severe or recurrent sinonasal aspergillosis.

Methods:A standard rhinotomy was performed on seven dogs. In the initial study, the bone flap was left attached cranially and replaced at the end of the procedure. In the main study group, the bone flap was discarded. Nasal passages were debrided and irrigated with enilconazole solution for one hour. Oral itraconazole was administered to four dogs for one month postoperatively. Follow‐up rhinoscopy was performed in all dogs.

Results:All three dogs in the initial study had recurrence of the disease and two dogs had a second surgery to remove the flap. The main study group included four dogs in which the flap was initially removed, and the two dogs from the initial study that required a second surgery. At follow‐up rhinoscopy, five dogs were free of aspergillus but had bacterial or inflammatory rhinitis and one dog had a small aspergilloma but was subsequently asymptomatic. Telephone follow‐up revealed that four dogs were asymptomatic, one dog had intermittent sneezing and serous nasal discharge, and one dog had intermittent epistaxis.

ClinicalSignificance:Rhinotomy with removal of the flap combined with one‐hour infusion of 2 per cent enilconazole and oral itraconazole resulted in satisfactory outcome in dogs with severe or recurrent aspergillosis.
A martial arts injury: karate induced unilateral haematoma of the adrenal gland
Authors: Ortu M , Vaccarezza M , Trovati S , Galli M , Gervasoni C
Published: May 2006

Adrenal gland haematoma is often a complication of traumatic events. The case is reported of a 45 year old man with unilateral non-symptomatic adrenal gland haematoma caused by a trauma during martial arts practice.
Relation between serum creatinine and body mass index in elite athletes of different sport disciplines
Authors: Banfi G , Del Fabbro M
Published: May 2006

Objectives:To document the relation between serum creatinine concentration and body mass index in elite athletes from five different sports, and to study potential differences among athletes performing different sports with different features and requirements.

Methods:Before the start of the competitive season, serum creatinine was measured in 151 elite athletes from five different sports: rugby (n  =  44), soccer (n  =  27), alpine skiing (n  =  34), sailing (n  =  22), cycling (n  =  24). Pearson’s correlation analysis was used to evaluate the relation between serum creatinine and body mass index (BMI). Analysis of variance and unpaired Student’sttest were used to compare creatinine concentration and BMI in different sport disciplines.

Results:In the whole group of athletes, a positive correlation between serum creatinine and BMI was found (r =  0.48, p<0.001). Significant differences in creatinine concentration and BMI were found between athletes competing in different sports: their mean (SD) values were respectively 1.31 (0.12) mg/dl and 28.83 (2.41) for rugby players, 1.27 mg/dl (0.10) and 23.10 (1.01) for soccer players, 1.15 (0.11) mg/dl and 25.8 (1.50) for skiers, 1.08 (0.11) mg/dl and 26.93 (2.36) for sailors, and 0.91 (0.07)mg/dl and 21.33 (1.21) for cyclists.

Conclusions:There is a correlation between creatinine concentration and BMI in elite athletes competing in different sports characterised by different kinds of training, competitive season, and involvement of aerobic and anaerobic metabolism. Interpretation of creatinine concentrations in male athletes should consider professional status as well as the specific sport performed. All athletes should be monitored with consecutive creatinine assessments, using as the baseline the concentration determined before the start of training and the competitive season, but taking into consideration the specific sport performed and the BMI until equations that include creatinine and factors that affect its concentration are used.
Concentric myocardial hypertrophy after one year of increased training volume in experienced distance runners
Authors: Venckunas T , Stasiulis A , Raugaliene R
Published: May 2006

Objectives:As evidence on the predominant type of cardiac hypertrophy due to endurance running training is inconsistent, the aim of this study was to investigate the effect of increased training volume on echocardiographic variables of distance runners.

Methods:Twenty three adult, experienced, male distance runners underwent standard two dimensionally guided M mode and Doppler echocardiography before and after a one year period during which they were randomly allocated to either control (n  =  11) or intervention (n  =  12) groups. The intervention group increased their training volume from (mean (SD)) 8.0 (3.0) to 12.5 (3.9) hours/week without increasing the intensity, and the controls changed neither training parameter.

Results:In the intervention group, training induced an increase in left ventricular (LV) mass (from 240.4 (53.8) to 279.5 (60.6) g, p<0.001) and LV mass index (from 126.7 (28.2) to 147.6 (32.3) g/m2, p<0.001) mainly due to an increase in end diastolic interventricular septum (from 10.4 (1.8) to 11.5 (1.7) mm, p<0.01) and LV posterior wall thickness (from 10.4 (1.6) to 11.5 (1.6) mm, p<0.001). No significant changes in LV internal diameter or measured indices of LV function occurred (p>0.05). The sum of the right ventricular diameter and wall thickness was greater after the increased volume training (p<0.05). None of the variables changed significantly in the control group (p>0.05).

Conclusions:In experienced, subelite distance runners, further increasing the training volume results in concentric cardiac hypertrophy.
Introducing tobacco cessation in developing countries: an overview of Project Quit Tobacco International
Authors: Nichter M
Published: May 2006

Project Quit Tobacco International is a pioneering attempt to develop culturally appropriate approaches to tobacco cessation within the health sectors of India and Indonesia. An overview of the formative research that contributed to intervention development is presented followed by a discussion of the research design adopted to evaluate the introduction of tobacco cessation in medical schools and clinics chosen for pilot testing. Four stages of research and implementation are described as a means of providing colleagues in developing countries with a prototype for future tobacco cessation research and training efforts.
Tobacco use in the Dominican Republic: understanding the culture first: Table 1
Authors: Dozier A M , Ossip-Klein D J , Diaz S , Chin N P , Sierra E , Quiñones Z , Dye T D , McIntosh S , Armstrong L
Published: May 2006

Objective:To conduct formative research on the landscape of tobacco use to guide survey and subsequent intervention development in the Dominican Republic (DR).

Design:Rapid Assessment Procedures, systematic qualitative methods (participant-observations, in-depth interviewing, focus groups) using bilingual mixed age and gendered teams from the United States and DR.

Subjects:Over 160 adults (men and women), ages 18 to 90 years, current, former and never smokers, community members and leaders from six underserved, economically disadvantaged DR communities.

Main outcome measures:Key domains: tobacco use patterns and attitudes; factors affecting smoking initiation, continuation, quitting; perceived risks/benefits/effects of smoking; and awareness/effects of advertising/regulations.

Results:Perceptions of prevalence varied widely. While “everybody” smokes, smokers or ex-smokers were sometimes difficult to find. Knowledge of health risks was limited to the newly mandated statement “Fumar es prejudicial para la salud” [Smoking is harmful to your health]. Smokers started due to parents, peers, learned lifestyle, fashion or as something to do. Smoking served as an escape, relaxation or diversion. Quit attempts relied on personal will, primarily for religious or medical reasons. Social smoking (custom or habit) (< 10 cigarettes per day) was viewed as a lifestyle choice rather than a vice or addiction. Out of respect, smokers selected where they smoked and around whom. Health care providers typically were reactive relative to tobacco cessation, focusing on individuals with smoking related conditions. Tobacco advertising was virtually ubiquitous. Anti-tobacco messages were effectively absent. Cultures of smoking and not smoking coexisted absent a culture of quitting.

Conclusions:Systematic qualitative methods provided pertinent information about tobacco attitudes and use to guide subsequent project steps. Integrating qualitative then quantitative research can be replicated in similar countries that lack empirical data on the cultural dimensions of tobacco use.
FIELD OF HOMOGENEOUS PLANE IN QUANTUM ELECTRODYNAMICS
Authors: FIALKOVSKI I. V. , MARKOV V. N. , PIS'MAK YU. M.
Published: May 2006

We study quantum electrodynamics coupled to the matter field on singular background, which we call defect. For defect on the infinite plane we calculated the fermion propagator and mean electromagnetic field. We show that at large distances from the defect plane, the electromagnetic field is constant what is in agreement with the classical results. The quantum corrections determining the field near the plane are calculated in the leading order of perturbation theory.
PT-SYMMETRY BREAKING HAMILTONIAN INTERACTIONS IN BF MODELS
Authors: CIOROIANU E. M. , SĂRARU S. C.
Published: May 2006

Starting with a finite collection of Abelian models, all consistent interactions (in n≥4 dimensions) that break the PT invariance are obtained by means of the Hamiltonian deformation procedure based on local BRST cohomology. This paper enhances one of our previous works, where only PT-invariant deformations were considered. The associated coupled theory is an interacting, topological BF model exhibiting an open gauge algebra and on-shell reducibility relations.
SIGNATURES OF NEW PHYSICS IN DILEPTONIC B-DECAYS
Authors: CHOUDHURY S. RAI , CORNELL A. S. , GAUR NAVEEN , JOSHI G. C.
Published: May 2006

Leptonic decays of B-mesons are theoretically very clean probes for testing the Standard Model (SM) and possible physics beyond it. Amongst the various leptonic decays of the B-meson, the pure dileptonic decay B → ℓ+ ℓ- is very important, as this mode is helicity suppressed in the SM but can be substantially enhanced in some of the models beyond the SM, such as supersymmetric (SUSY) theories and the two Higgs doublet model (2HDM). Although the purely dileptonic decay mode is helicity suppressed in the SM its associated mode B → ℓ+ ℓ-γ does not have the same suppression, due to the presence of γ in the final state. In this paper we will also analyze the effects of enhanced Z-penguins on these two decay modes.
PERELOMOV AND BARUT–GIRARDELLO SU(1, 1) COHERENT STATES FOR HARMONIC OSCILLATOR IN ONE-DIMENSIONAL HALF SPACE
Authors: LIU Q. H. , ZHUO H.
Published: May 2006

The Perelomov and the Barut–Girardello SU(1, 1) coherent states for harmonic oscillator in one-dimensional half space are constructed. Results show that the uncertainty products ΔxΔp for these two coherent states are bound from below [Formula: see text] that is the uncertainty for the ground state, and the mean values for position x and momentum p in classical limit go over to their classical quantities respectively. In classical limit, the uncertainty given by Perelomov coherent does not vanish, and the Barut–Girardello coherent state reveals a node structure when positioning closest to the boundary x = 0 which has not been observed in coherent states for other systems.
THE POLARIZATION OF THE COSMIC MICROWAVE BACKGROUND DUE TO PRIMORDIAL GRAVITATIONAL WAVES
Authors: KEATING BRIAN G. , POLNAREV ALEXANDER G. , MILLER NATHAN J. , BASKARAN DEEPAK
Published: May 2006

We review current observational constraints on the polarization of the Cosmic Microwave Background (CMB), with a particular emphasis on detecting the signature of primordial gravitational waves. We present an analytic solution to the Polanarev approximation for CMB polarization produced by primordial gravitational waves. This simplifies the calculation of the curl, or B-mode power spectrum associated with gravitational waves during the epoch of cosmological inflation. We compare our analytic method to existing numerical methods and also make predictions for the sensitivity of upcoming CMB polarization observations to the inflationary gravitational wave background. We show that upcoming experiments should be able either detect the relic gravitational wave background or completely rule out whole classes of inflationary models.
Endothelial response to stress from exogenous Zn2+ resembles that of NO-mediated nitrosative stress, and is protected by MT-1 overexpression
Authors: Wiseman Dean A. , Wells Sandra M. , Wilham Jason , Hubbard Maryann , Welker Jonathan E. , Black Stephen M.
Published: May 2006

While nitric oxide (NO)-mediated biological interactions have been intensively studied, the underlying mechanisms of nitrosative stress with resulting pathology remain unclear. Previous studies have demonstrated that NO exposure increases free zinc ions (Zn2+) within cells. However, the resulting effects on endothelial cell survival have not been adequately resolved. Thus the purpose of this study was to investigate the role of altered zinc homeostasis on endothelial cell survival. Initially, we confirmed the previously observed significant increase in free Zn2+ with a subsequent induction of apoptosis in our pulmonary artery endothelial cells (PAECs) exposed to the NO donor N-[2-aminoethyl]- N-[2-hydroxy-2-nitrosohydrazino]-1,2-ethylenediamine. However, NO has many effects upon cell function and we wanted to specifically evaluate the effects mediated by zinc. To accomplish this we utilized the direct addition of zinc chloride (ZnCl2) to PAEC. We observed that Zn2+-exposed PAECs exhibited a dose-dependent increase in superoxide (O2−·) generation that was localized to the mitochondria. Furthermore, we found Zn2+-exposed PAECs exhibited a significant reduction in mitochondrial membrane potential, loss of cardiolipin from the inner leaflet, caspase activation, and significant increases in TdT-mediated dUTP nick end labeling-positive cells. Furthermore, using an adenoviral construct for the overexpression of the Zn2+-binding protein, metallothionein-1 (MT-1), we found either MT-1 overexpression or coincubation with a Zn2+-selective chelator, N, N,N′, N′-tetrakis(2-pyridylmethyl)ethylene-diamide, in PAECs significantly protected the mitochondria from both NO and Zn2+-mediated disruption and induction of apoptosis and cell death. In summary, our results indicate that a loss of Zn2+ homeostasis produces mitochondrial dysfunction, increased oxidative stress, and apoptotic cell death. We propose that regulation of Zn2+ levels may represent a potential therapeutic target for disease associated with both nitrosative and oxidative stress.
ANG II-induced cell proliferation is dually mediated by c-Src/Yes/Fyn-regulated ERK1/2 activation in the cytoplasm and PKCζ-controlled ERK1/2 activity within the nucleus
Authors: Godeny Michael D. , Sayeski Peter P.
Published: May 2006

High-affinity binding of angiotensin II (ANG II) to the ANG II type 1 receptor (AT1R) results in the activation of ERK1/2 mitogen-activated protein kinases (MAPK). However, the precise mechanism of ANG II-induced ERK1/2 activation has not been fully characterized. Here, we investigated the signaling events leading to ANG II-induced ERK1/2 activation using a c-Src/Yes/Fyn tyrosine kinase-deficient mouse embryonic fibroblast (MEF) cell line stably transfected with the AT1R (SYF/AT1). ERK1/2 activation was reduced by ∼50% within these cells compared with wild-type controls (WT/AT1). The remaining ∼50% of intracellular ERK1/2 activation was dependent upon heterotrimeric G protein and protein kinase C zeta (PKCζ) activation. Therefore, ANG II-induced ERK1/2 activation occurs via two independent mechanisms. We next investigated whether a loss of either c-Src/Yes/Fyn or PKCζ signaling affected ERK1/2 nuclear translocation and cell proliferation in response to ANG II. ANG II-induced cell proliferation was markedly reduced in SYF/AT1 cells compared with WT/AT1 cells ( P < 0.01), but interestingly, ERK2 nuclear translocation was normal. ANG II-induced nuclear translocation of ERK2 was blocked via pretreatment of WT/AT1 cells with a PKCζ pseudosubstrate. ANG II-induced cell proliferation was significantly reduced in PKCζ pseudosubstrate-treated WT/AT1 cells ( P < 0.01) and was completely blocked in SYF/AT1 cells treated with this same compound. Thus ANG II-induced cell proliferation appears to be regulated by both ERK1/2-driven nuclear and cytoplasmic events. In response to ANG II, the ability of ERK1/2 to remain within the cytoplasm or translocate into the nucleus is controlled by c-Src/Yes/Fyn or heterotrimeric G protein/PKCζ signaling, respectively.
ERK1/2 regulates ANG II-dependent cell proliferation via cytoplasmic activation of RSK2 and nuclear activation of elk1
Authors: Godeny Michael D. , Sayeski Peter P.
Published: May 2006

In a concurrently submitted article, we show that ANG II-induced ERK1/2 activation is mediated by both c-Src/Yes/Fyn and heterotrimeric G protein/PKCζ-dependent signaling. Furthermore, we show that heterotrimeric G protein/PKCζ-activated ERK1/2 is destined for the nucleus while ERK1/2 activated by c-Src/Yes/Fyn-dependent signaling remains in the cytoplasm. Interestingly, both mechanisms of activation are required for maximum ANG II-induced cell proliferation. In this study, we sought to determine the mechanisms by which ERK1/2 facilitate cell proliferation via these distinct nuclear and cytoplasmic events, using cells that were lacking either c-Src/Yes/Fyn or heterotrimeric G protein/PKCζ-dependent ERK1/2 activation. A loss of c-Src/Yes/Fyn blocked ANG II-dependent RSK2 activation, RSK2 nuclear translocation, serum-response factor (SRF) phosphorylation, a portion of c-fos transcriptional activity and c-Fos phosphorylation. Blocking ANG II-induced heterotrimeric G protein/PKCζ activity resulted in a loss of ERK1/2 nuclear translocation, elk1 phosphorylation, and the remaining portion of c-fos transcriptional activity not dependent on c-Src/Yes/Fyn. Inhibition of RSK with the potent and selective inhibitor, SL0101, attenuated ANG II-induced cell proliferation, and, in combination with a PKCζ pseudosubstrate, completely attenuated cell proliferation. Thus we conclude that ERK1/2 mediate ANG II-dependent cell proliferation via distinct cytoplasmic and nuclear signaling events, which are in turn governed by c-Src/Yes/Fyn and heterotrimeric G protein/PKCζ-dependent signaling, respectively.
Integration of rapid cytosolic Ca2+ signals by mitochondria in cat ventricular myocytes
Authors: Sedova Marina , Dedkova Elena N. , Blatter Lothar A.
Published: May 2006

Decoding of fast cytosolic Ca2+ concentration ([Ca2+]i) transients by mitochondria was studied in permeabilized cat ventricular myocytes. Mitochondrial [Ca2+] ([Ca2+]m) was measured with fluo-3 trapped inside mitochondria after removal of cytosolic indicator by plasma membrane permeabilization with digitonin. Elevation of extramitochondrial [Ca2+] ([Ca2+]em) to >0.5 μM resulted in a [Ca2+]em-dependent increase in the rate of mitochondrial Ca2+ accumulation ([Ca2+]em resulting in half-maximal rate of Ca2+ accumulation = 4.4 μM) via Ca2+ uniporter. Ca2+ uptake was sensitive to the Ca2+ uniporter blocker ruthenium red and the protonophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone and depended on inorganic phosphate concentration. The rates of [Ca2+]m increase and recovery were dependent on the extramitochondrial [Na+] ([Na+]em) due to Ca2+ extrusion via mitochondrial Na+/Ca2+ exchanger. The maximal rate of Ca2+ extrusion was observed with [Na+]em in the range of 20–40 mM. Rapid switching (0.25–1 Hz) of [Ca2+]em between 0 and 100 μM simulated rapid beat-to-beat changes in [Ca2+]i (with [Ca2+]i transient duration of 100–500 ms). No [Ca2+]m oscillations were observed, either under conditions of maximal rate of Ca2+ uptake (100 μM [Ca2+]em, 0 [Na+]em) or with maximal rate of Ca2+ removal (0 [Ca2+]em, 40 mM [Na+]em). The slow frequency-dependent increase of [Ca2+]m argues against a rapid transmission of Ca2+ signals between cytosol and mitochondria on a beat-to-beat basis in the heart. [Ca2+]m changes elicited by continuous or pulsatile exposure to elevated [Ca2+]em showed no difference in mitochondrial Ca2+ uptake. Thus in cardiac myocytes fast [Ca2+]i transients are integrated by mitochondrial Ca2+ transport systems, resulting in a frequency-dependent net mitochondrial Ca2+ accumulation.
Decreased gastric mechanodetection, but preserved gastric emptying, in CCK-1 receptor-deficient OLETF rats
Authors: De Jonghe Bart C. , Hajnal Andras , Covasa Mihai
Published: May 2006

Obese CCK-1 receptor-lacking Otsuka Long Evans Tokushima fatty (OLETF) rats are hyperphagic relative to control, nonmutant Long Evans Tokushima Otsuka (LETO) rats. This study sought to assess whether the overeating observed in OLETF rats is associated with changes in gastric emptying rates or detection of gastric volume. We performed experiments in both 12- and 29-wk-old OLETF and LETO rats to address possible alterations in gastric functions during the development of increased body weight and blood glucose abnormalities in OLETF rats. Gastric emptying of a 5-g solid chow test meal was not significantly different between strains at either 1, 2, or 4 h postmeal. When rats with ad libitum access to chow were tested, there were no significant differences in gastric emptying between strains at any time period despite OLETF rats consuming significantly more chow than LETO rats. Similar to solid food, 5-min gastric emptying of a 5-ml isosmotic and hyperosmotic saline or glucose load was not significantly different between strains. When the stomach was distended with a 15-ml semisolid chow load, there was no significance difference in emptying at either 1 or 2 h. No significant differences in gastric emptying were detected between 12- and 29-wk-old rats under any conditions. Both young and old OLETF rats, however, reduced sham intake significantly less compared with LETO rats during a brief period of gastric distension by 5- or 10-ml balloon inflation. Finally, OLETF rats showed decreased Fos expression in the nucleus of the solitary tract relative to LETO rats after an 8-ml gastric distension. These findings demonstrate that OLETF rats do not express deficits in controlling gastric emptying rates; however, they exhibit decreased behavioral and vagal responsiveness to gastric distension that may contribute to the increased meal size in these animals.
Propofol and thiopental attenuate adenosine triphosphate-sensitive potassium channel relaxation in pulmonary veins
Authors: Roh Woon-Seok , Ding Xueqin , Murray Paul A.
Published: May 2006

Pulmonary veins (PV) make a significant contribution to total pulmonary vascular resistance. We investigated the cellular mechanisms by which the intravenous anesthetics propofol and thiopental alter adenosine triphosphate-sensitive potassium (KATP+) channel relaxation in canine PV. The effects of KATP+ channel inhibition (glybenclamide), cyclooxygenase inhibition (indomethacin), nitric oxide synthase inhibition (l-NAME), and L-type voltage-gated Ca2+ channel inhibition (nifedipine) on vasorelaxation responses to levcromakalim (KATP+ channel activator) alone and in combination with the anesthetics were assessed. The maximal relaxation response to levcromakalim was attenuated by removing the endothelium and by l-NAME, but not by indomethacin. Propofol (10−5, 3 × 10−5, and 10−4 M) and thiopental (10−4 and 3 × 10−4 M) each attenuated levcromakalim relaxation in endothelium-intact (E+) rings, whereas propofol (3 × 10−5 and 10−4 M) and thiopental (3 × 10−4 M) attenuated levcromakalim relaxation in endothelium-denuded (E−) rings. In E+ rings, the anesthesia-induced attenuation of levcromakalim relaxation was decreased after pretreatment with l-NAME but not with indomethacin. In E-strips, propofol (10−4 M) and thiopental (3 × 10−4 M) inhibited decreases in tension and intracellular Ca2+ concentration ([Ca2+]i) in response to levcromakalim, and these changes were abolished by nifedipine. These findings indicate that propofol and thiopental attenuate the endothelium-dependent component of KATP+ channel-induced PV vasorelaxation via an inhibitory effect on the nitric oxide pathway. Both anesthetics also attenuate the PV smooth muscle component of KATP+ channel-induced relaxation by reducing the levcromakalim-induced decrease in [Ca2+]i via an inhibitory effect on L-type voltage-gated Ca2+ channels.
Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK-dependent mechanism
Authors: Wang Meijing , Crisostomo Paul R. , Herring Christine , Meldrum Kirstan K. , Meldrum Daniel R.
Published: May 2006

Accumulating evidence suggests that progenitor cells may decrease destructive inflammation and reduce tissue loss by antiapoptotic mechanisms. However, they remain poorly characterized, and many questions remain regarding the mechanisms by which they may positively affect wound healing, tissue remodeling, or tissue regeneration. It has been speculated that various growth factors are responsible, but what components of the wound milieu stimulate progenitor cell production of growth factors and by what mechanisms? We hypothesized that tumor necrosis factor-α (TNF-α) stimulated progenitor cell secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and insulin-like growth factor I (IGF-I) by a p38 mitogen-activated protein kinase (MAPK)-dependent mechanism. Human mesenchymal stem cells (hMSCs) and human adipose progenitor cells (hAPCs) were divided into four groups: control, p38 MAPK inhibitor (p38MKI), TNF, and TNF + p38MKI. After 24 h of incubation, supernatants were harvested for ELISA of VEGF, HGF, and IGF-I. Cells were collected for Western blot analysis of p38 MAPK activation. Secretion of VEGF, HGF, and IGF-I in hMSCs and hAPCs was significantly increased by stimulation with TNF and was associated with increased activation of p38 MAPK. The p38 MAPK inhibitor decreased production of TNF-stimulated VEGF, HGF, and IGF-I in hMSCs and hAPCs. However, p38 MAPK inhibitor alone had no effect on production of growth factors. These data demonstrate that progenitor cells are potent sources of VEGF, HGF, and IGF-I. TNF, a prominent tissue cytokine, strongly stimulated production of growth factors by hMSCs and hAPCs via a p38 MAPK-dependent mechanism.
Amperometric Study of the Kinetics of Exocytosis in Mouse Adrenal Slice Chromaffin Cells: Physiological and Methodological Insights
Authors: Arroyo Gloria , Fuentealba Jorge , Sevane-Fernández Natalia , Aldea Marcos , García Antonio G. , Albillos Almudena
Published: May 2006

This study was designed to examine the kinetics of neurotransmitter release using the carbon fiber amperometric technique on cells in slices of mouse adrenal glands superfused with bicarbonate phosphate buffer–based solutions. The exocytotic amperometric response evoked by electrical stimulation was significantly faster than that produced after exogenous application of ACh or K+. Splanchnic nerve–evoked neurotransmitter release was blocked by hexamethonium, indicating the involvement of ACh nicotinic receptors. We discuss the implications of our data for understanding the mechanisms underlying the vesicle fusion process.
Sphingosine-1-Phosphate Via Activation of a G-Protein-Coupled Receptor(s) Enhances the Excitability of Rat Sensory Neurons
Authors: Zhang Y. H. , Fehrenbacher J. C. , Vasko M. R. , Nicol G. D.
Published: May 2006

Sphingosine-1-phosphate (S1P) is released by immune cells and is thought to play a key role in chemotaxis and the onset of the inflammatory response. The question remains whether this lipid mediator also contributes to the enhanced sensitivity of nociceptive neurons that is associated with inflammation. Therefore we examined whether S1P alters the excitability of small diameter, capsaicin-sensitive sensory neurons by measuring action potential (AP) firing and two of the membrane currents critical in regulating the properties of the AP. External application of S1P augments the number of APs evoked by a depolarizing current ramp. The enhanced firing is associated with a decrease in the rheobase and an increase in the resistance at firing threshold although neither the firing threshold nor the resting membrane potential are changed. Treatment with S1P enhanced the tetrodotoxin-resistant sodium current and decreased the total outward potassium current ( IK). When sensory neurons were internally perfused with GDP-β-S, a blocker of G protein activation, the S1P-induced increase in APs was completely blocked and suggests the excitatory actions of S1P are mediated through G-protein-coupled receptors called endothelial differentiation gene or S1PR. In contrast, internal perfusion with GDP-β-S and S1P increased the number of APs evoked by the current ramp. These results and our finding that the mRNAs for S1PRs are expressed in both the intact dorsal root ganglion and cultures of adult sensory neurons supports the notion that S1P acts on S1PRs linked to G proteins. Together these findings demonstrate that S1P can regulate the excitability of small diameter sensory neurons by acting as an external paracrine-type ligand through activation of G-protein-coupled receptors and thus may contribute to the hypersensitivity during inflammation.
Influence of Visual Motion on Tactile Motion Perception
Authors: Bensmaïa S. J. , Killebrew J. H. , Craig J. C.
Published: May 2006

Subjects were presented with pairs of tactile drifting sinusoids and made speed discrimination judgments. On some trials, a visual drifting sinusoid, which subjects were instructed to ignore, was presented simultaneously with one of the two tactile stimuli. When the visual and tactile gratings drifted in the same direction (i.e., from left to right), the visual distractors were found to increase the perceived speed of the tactile gratings. The effect of the visual distractors was proportional to their temporal frequency but not to their perceived speed. When the visual and tactile gratings drifted in opposite directions, the distracting effect of the visual distractors was either substantially reduced or, in some cases, reversed (i.e., the distractors slowed the perceived speed of the tactile gratings). This result suggests that the observed visual-tactile interaction is dependent on motion and not simply on the oscillations inherent in drifting sinusoids. Finally, we find that disrupting the temporal synchrony between the visual and tactile stimuli eliminates the distracting effect of the visual stimulus. We interpret this latter finding as evidence that the observed visual-tactile interaction operates at the sensory level and does not simply reflect a response bias.
Muscle-Pair Specific Distribution and Grip-Type Modulation of Neural Common Input to Extrinsic Digit Flexors
Authors: Winges Sara A. , Johnston Jamie A. , Santello Marco
Published: May 2006

To gain insight into the synergistic control of hand muscles, we have recently quantified the strength of correlated neural activity across motor units from extrinsic digit flexors during a five-digit object-hold task. We found stronger synchrony and coherence across motor units from thumb and index finger flexor muscle compartment than between the thumb flexor and other finger flexor muscle compartments. The present study of two-digit object hold was designed to determine the extent to which such distribution of common input among thumb-finger flexor muscle compartments, revealed by holding an object with five digits, is preserved when varying the functional role of a given digit pair. We recorded normal force exerted by the digits and electrical activity of single motor units from muscle flexor pollicis longus (FPL) and two compartments of the m. flexor digitorum profundus (FDP2 and FDP3; index and middle finger, respectively). Consistent with our previous results from five-digit grasping, synchrony and coherence across motor units from FPL-FDP2 was significantly stronger than in FPL-FDP3 during object hold with two digits [common input strength: 0.49 ± 0.02 and 0.35 ± 0.02 (means ± SE), respectively; peak coherence: 0.0054 and 0.0038, respectively]. This suggests that the distribution of common neural input is muscle-pair specific regardless of grip type. However, the strength of coherence, but not synchrony, was significantly stronger in two- versus five-digit object hold for both muscle combinations, suggesting the periodicity of common input is sensitive to grip type.
The Stratified Pulson
Authors: Rubino Angelo , Dotsenko Sergey
Published: May 2006

New analytical nonstationary circular eddy solutions of the nonlinear, reduced-gravity shallow-water equations in a multilayer stratified rotating ocean are presented. The new solutions extend previous “pulson” analytical solutions, which describe circular oscillating lenslike warm core eddies in a reduced-gravity homogeneous ocean on the f plane, to arbitrary stable vertical stratifications within surface as well as intermediate vortices. As a result, cyclonic as well as anticyclonic horizontal swirl velocities can coexist on different vortex layers within parts of an inertial period, while vertical distributions of the vortex mean tangential velocity resembling observed vertical velocity distributions of surface as well as intermediate lenslike vortices are obtained. The dynamics of a two-layer pulson is discussed and it is shown that, for nonnegligible lower- and upper-layer thickness, its total water transport substantially differs from the total water transport of the corresponding homogeneous pulson. In linearly stratified warm core vortices it is found that the amplitude of the temporal oscillation of the azimuthal velocity is maximum in the bottom layer and decreases toward the surface, while the mean azimuthal velocity is minimum in the bottom layer and increases toward the surface. In linearly stratified intermediate vortices it is found that the mean azimuthal velocity is no longer a monotonic function of the water depth: it is maximum at the top and at the bottom of the vortex and minimum at the vortex central depth. The new solutions add realism to known analytical vortex solutions and elucidate aspects of the observed complexity of geophysical vortex motions.
Temperature Advection by Tropical Instability Waves
Authors: Jochum Markus , Murtugudde Raghu
Published: May 2006

A numerical model of the tropical Pacific Ocean is used to investigate the processes that cause the horizontal temperature advection of tropical instability waves (TIWs). It is found that their temperature advection cannot be explained by the processes on which the mixing length paradigm is based. Horizontal mixing of temperature across the equatorial SST front does happen, but it is small relative to the “oscillatory” temperature advection of TIWs. The basic mechanism is that TIWs move water back and forth across a patch of large vertical entrainment. Outside this patch, the atmosphere heats the water and this heat is then transferred into the thermocline inside the patch. These patches of strong localized entrainment are due to equatorial Ekman divergence and due to thinning of the mixed layer in the TIW cyclones. The latter process is responsible for the zonal temperature advection, which is as large as the meridional temperature advection but has not yet been observed. Thus, in the previous observational literature the TIW contribution to the mixed layer heat budget may have been underestimated significantly.