bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of prostaglandin G/H synthase (PGHS) and heat shock protein-70 (HSP-70) in the corpus luteum (CL) of prostaglandin F2α-treated immature superovulated rats
Authors: Narayansingh R M , Senchyna M , Vijayan M M , Carlson J C
Published: September 2004

In this study we examined the mechanism of corpus luteum (CL) regression by measuring changes in expression of prostaglandin G/H synthase-1 (PGHS-1) and -2 (PGHS-2) in day 4 CL and inducible heat shock protein 70 (HSP-70) in day 4 and day 9 CL of immature superovulated rats. The rats were superovulated and treated with 500 µg of prostaglandin F2α(PGF2α) on day 4 or day 9 after CL formation. Ovaries and serial blood samples were removed during the 24-hour period following treatment. Plasma progesterone was determined by radioimmunoassay while mRNA abundance and protein expression were assessed by semiquantitative RT-PCR and immunoblot analysis, respectively. One hour after PGF2α, both day 4 and day 9 rats exhibited a significant decrease in progesterone secretion; however, there was a greater decrease in day 9 rats. In ovarian samples removed on day 4, there was a significant increase in mRNA for PGHS-2 at 1 hour after PGF2α. PGHS-1 mRNA content remained unchanged. Immunoblot analyses showed an increase in PGHS-2 protein expression only at 8 h. There were no changes in PGHS-1 protein expression. In day 9 rats, ovarian HSP-70 protein levels increased by 50% after PGF2αinjection; however, on day 4 there was no change in expression of this protein over the sampling period. These results suggest that expression of PGHS-2 may be involved in inhibiting progesterone production and that expression of HSP-70 may be required for complete CL regression in the rat.Key words: rat, prostaglandin F2α, corpus luteum, prostaglandin G/H synthase, heat shock protein-70.
Permeability to water in a tight epithelium: possible modulating action of gap junctions
Authors: Orce Gabriel , Castillo Graciela , Chanampa Yolanda , Bellomio Alejandra
Published: September 2004

Osmotic water flow (Jw) across tight distal nephron epithelial membranes increases upon exposure to vasopressin: following binding of the hormone to its receptors, intracellular cyclic AMP concentration increases, leading to insertion of aquaporins in the apical membrane. The involvement of intercellular communication in the process, however, has not been adequately explored. Octanol, 1.2 × 103 M, a gap junction inhibitor, significantly reduced Jw (expressed as mg·20 min1) in isolated toad urinary bladders (a model of the distal nephron) subjected to a transepithelial osmotic gradient and exposed to agents mimicking the vasopressin-triggered mechanism: oxytocin, 50 mIU·mL1 (from 185.3 ± 28.0, P < 0.001, to 69.0 ± 23.6, P < 0.05; Pdiff < 0.01, n = 6), and cyclic AMP, 2.5 × 103 M (from 98.0 ± 32.6, P < 0.02, to 31.0 ± 13.9, NS; Pdiff < 0.05, n = 12), without altering the effect of nystatin, 450 U·mL1, which increases Jw via a mechanism unrelated to apical aquaporin insertion (163.2 ± 16.3, P < 0.001, in controls vs. 150.3 ± 10.4, P < 0.001, in octanol-treated bladders; Pdiff: NS, n = 6). Another gap junction blocker, carbenoxolone, 2.0 × 104 M (CBX), exerted similar effects on the responses to oxytocin, 100 mIU·mL1, reducing the response from 256.7 ± 33.6, P < 0.001, to 102.7 ± 10.4, P < 0.001; Pdiff < 0.01, n = 6) and nystatin, which was unaffected (95.0 ± 20.9, P < 0.01, vs. 132.0 ± 27.0, P < 0.01; Pdiff: NS, n = 6). Our results suggest that either gap junctions or, alternatively, unapposed gap junction hemichannels, may be important in the regulation of Jw in the isolated toad bladder, by modulating a step in the physiological process leading to increased apical membrane permeability. Key words: Bufo arenarum, toad urinary bladder, water flow, epithelial permeability, n-octanol, carbenoxolone.
An indomethacin-sensitive contraction induced by β-antagonists in guinea pig airways
Authors: Johansson Fredrik , Andersson Rolf G.G , Lindström Eva , Svensson Samuel S
Published: September 2004

β-adrenergic receptor (β-AR) antagonists have been associated with increased airway reactivity in asthmatics and potentiation of contractile stimuli in animal models. In the present study, using an in vitro model of tracheal preparations from guinea pigs, we show that the β-AR antagonists propranolol and pindolol induce a smooth muscle contraction. A prerequisite for this contraction is that the airway preparations have been pre-treated with an β-AR agonist. Our data show that the contractile effect of β-AR antagonists is not a simple consequence of reversing the agonist-induced relaxation. Furthermore, the effect seems to be mediated through interaction with β2-ARs since the response is stereo-selective, and the selective β1-AR receptor antagonist atenolol did not induce any contractile response. SQ 29,546, a thromboxane A2 antagonist; MK 886, a lipoxygenase inhibitor; and indomethacin, a cyclooxygenase inhibitor significantly inhibited the contractions of the tracheal preparations induced with propranolol or pindolol. We put forward the hypothesis that the contractile effect of the β-AR antagonist is a consequence of their inverse agonist activity, which is only evident when the receptor population have a higher basal activity. Our results indicate a novel additional explanation for the known side effect, bronchoconstriction, of β-AR antagonist.Key words: beta antagonist, guinea pig trachea, propranolol, formoterol, pindolol, indomethacin.
Endoxin-mediated myocardial ischemia reperfusion injury in rats in vitro
Authors: Ke Yong-Sheng , Wang He-Gui , Wang De-Guo , Zhang Gen-Bao
Published: September 2004

Myocardial ischemia reperfusion results in an increase in intracellular sodium concentration, which secondarily increases intracellular calcium via Na+-Ca2+exchange, resulting in cellular injury. Endoxin is an endogenous medium of digitalis receptor and can remarkably inhibit Na+/K+-ATPase activity. Although the level of plasma endoxin is significantly higher during myocardial ischemia, its practical significance is unclear. This research is to investigate whether endoxin is one of important factors involved in myocardial ischemia reperfusion injury. Ischemia reperfusion injury was induced by 30 min of global ischemia and 30 min of reperfusion in isolated rat hearts. Heart rate (HR), left ventricular developed pressure (LVDP), and its first derivative (±dp/dtmax) were recorded. The endoxin contents, intramitochondrial Ca2+contents, and the Na+/K+-ATPase activity in myocardial tissues were measured. Myocardial damages were evaluated by electron microscopy. The endoxin and intramitochondrial Ca2+contents in myocardial tissues were remarkably higher, myocardial membrane ATPase activity was remarkably lower, the cardiac function was significantly deteriorated, and myocardial morphological damages were severe in myocardial ischemia reperfusion group vs. control. Anti-digoxin antiserum (10, 30 mg/kg) caused a significant improvement in cardiac function (LVDP and ±dp/dtmax), Na+/K+-ATPase activity, and myocardial morphology, and caused a reduction of endoxin and intramitochondrial Ca2+contents in myocardial tissues. In the present study, the endoxin antagonist, anti-digoxin antiserum, protected the myocardium against the damages induced by ischemia reperfusion in isolated rat hearts. The results suggest that endoxin might be one of main factors mediating myocardial ischemia reperfusion injury.Key words: endoxin, anti-digoxin antiserum, myocardial reperfusion injury, morphological evaluation, Na+/K+-exchanging ATPase.
Pyruvate prevents cardiac dysfunction and AMP-activated protein kinase activation by hydrogen peroxide in isolated rat hearts
Authors: Leon Hernando , Atkinson Laura L , Sawicka Jolanta , Strynadka Ken , Lopaschuk Gary D , Schulz Richard
Published: September 2004

Ischemia-reperfusion injury in the heart results in enhanced production of H2O2and activation of AMP-activated protein kinase (AMPK). Since mutations in AMPK result in cardiovascular dysfunction, we investigated whether the activation of AMPK mediates the H2O2-induced reduction in cardiac mechanical function. Isolated working rat hearts were perfused at 37 °C with Krebs-Henseleit solution. Following a 20-minute equilibration period, a single bolus of H2O2(300 µmol/L) was added and the hearts were perfused for an additional 5 min. H2O2induced a dramatic and progressive reduction in cardiac function. This was accompanied by rapid and significant activation of AMPK, an increase in Thr-172 phosphorylation of AMPK, and an increase in the creatine to phosphocreatine (Cr/PCr) ratio. Addition of pyruvate (5 mmol/L) to the perfusate prevented the H2O2-mediated reduction in cardiac mechanical dysfunction, activation of myocardial AMPK activity, increase in AMPK phosphorylation and the increase in the Cr/PCr ratio. Hearts challenged with H2O2(300 µmol/L) in presence of either AMPK inhibitor Compound C (10 µmol/L) or its vehicle (dimethyl sulfoxide (DMSO), 0.1%) showed reduced impairment in cardiac mechanical function. Compound C but not its vehicle significantly inhibited myocardial AMPK activity. Thus, H2O2induces cardiac dysfunction via both AMPK-dependent and independent mechanisms.Key words: oxidative stress, AMPK, antioxidant, isolated rat heart, pyruvate.
Subspecies discrimination in the Scandinavian beaver (Castor fiber): combining behavioral and chemical evidence
Authors: Rosell Frank , Steifetten Øyvind
Published: September 2004

Geographic isolation is one of several models that has been proposed to explain the evolutionary course of speciation. In this study, we examined how geographical isolation may affect subspecies discrimination in the free-ranging Scandinavian beaver (Castor fiber fiber L., 1758) by simulating a territorial intrusion by using scent (castoreum and anal gland secretion) from a con-subspecific (N = 8 for castoreum and N = 7 for anal gland secretion) and a hetero-subspecific (Castor fiber albicus Matschie, 1907; N = 2 for both castoreum and anal gland secretion). Direct observations of 33 families during evenings showed that beavers (i) sniffed castoreum but not anal gland secretion from C. f. fiber significantly longer than from C. f. albicus and (ii) responded aggressively (i.e., stood on the mound on their hind feet, pawing and (or) overmarking) significantly longer to castoreum but not anal gland secretion from C. f. fiber than from C. f. albicus. When experimental scent mounds were allowed to remain overnight, the response was significantly stronger to castoreum but not to anal gland secretion from C. f. fiber than from C. f. albicus. Gas chromatographic comparisons of castoreum and anal gland secretion from the two subspecies supported our behavioral observations for castoreum but not for anal gland secretion. These findings suggest that geographical isolation has developed discriminatory abilities in C. f. fiber. We further suggest that the proximate factors involved are of environmental origin.
Escarpia southwardae sp. nov., a new species of vestimentiferan tubeworm (Annelida, Siboglinidae) from West African cold seeps
Authors: Andersen Ann C , Hourdez S , Marie B , Jollivet D , Lallier F H , Sibuet M
Published: September 2004

A new species of vestimentiferan tubeworm belonging to the genus Escarpia is described from cold seeps off the western coast of Africa. The description is based on two collections (one of 180 animals, the other of 30 animals) using both morphological and molecular techniques. Morphologically, the African tubeworms are very similar to Escarpia laminata Jones, 1985 but differ from all other escarpids by the lack of branchial pinnules, a unique feature among vestimentiferans. Molecular evidence from sequences of the cytochrome-c oxidase subunit I gene places the species in the escarpid clade, closely related to E. laminata and Escarpia spicata Jones, 1985, but fails to discriminate among the three species. Four morphotypes are identified in the African species, corresponding to the four permutations of the following characters: presence or absence of an axial rod on the obturaculum and presence or absence of a split on the posterior ventral margin of the vestimentum. However, molecular data could not distinguish them as separate species. We suggest that the lack of an axial rod reflects predation. Biometrical data indicate a discontinuous recruitment period, as is known for other vestimentiferan species. Sex ratios are balanced, but females tend to be larger than males. We hypothesize that the males grow more slowly or die younger than the females.
Influence of gut morphology on passive transport of freshwater bryozoans by waterfowl in Doñana (southwestern Spain)
Authors: Figuerola Jordi , Green Andy J , Black Katrina , Okamura Beth
Published: September 2004

Waterbirds have been proposed as important vectors for the passive dispersal of those aquatic invertebrates and plants that lack a capacity for active dispersal between isolated water bodies. We analysed the frequency of internal transport of bryozoan propagules (statoblasts) by waterbirds in Doñana, Spain, by examining their presence in the intestines and ceca of dead birds and analysing the role of different aspects of gut characteristics in explaining variation in the presence/absence and abundance of statoblasts. Of the 228 samples examined, 7.9% presented intact statoblasts of Plumatella fungosa (Pallas, 1768), Plumatella emarginata Allman, 1844, and two unidentified Plumatella species. For a given bird species, individuals with heavier gizzards and shorter ceca had a lower incidence and abundance of statoblasts in the lower gut. Grit mass and intestine length were unrelated to the presence or abundance of statoblasts. Our results suggest that waterbirds frequently transport bryozoans on a local scale, with lighter gizzards and longer ceca favouring such transport. Lighter gizzards are likely to destroy fewer propagules before they reach the lower gut. Species and individuals with longer ceca are particularly good candidates for long-distance dispersal of bryozoans, given the longer passage time of propagules that enter the ceca.
Andiorrhinus (Andiorrhinus) kuru sp. nov. (Oligochaeta: Glossoscolecidae), a giant earthworm as food resource for Makiritare Indians of the Alto Rio Padamo, Amazonas, Venezuela
Authors: Moreno Ana G , Paoletti Maurizio G
Published: September 2004

A new species, Andiorrhinus (Andiorrhinus) kuru sp. nov., of Glossoscolecidae (Oligochaeta) from the Alto Orinoco, Amazonas, Venezuela, is described. The Makiritare Indians traditionally consume this species of earthworm together with another one called motto (Andiorrhinus (Amazonidrilus) motto Righi and Araujo, 1999) and a few other caterpillars, termites, aquatic insects, and weevill larvae. Andiorrhinus (A.) kuru is a large terrestrial earthworm living in the upland forest of the high river Padamo. The Makiritare collect it by digging into the soil with machetes. The species lives 10–20 cm deep in the soil close to the root mat of the trees.
Comparing the freezing susceptibility of third-instar larvae of Gnorimus variabilis (Cetoniidae: Trichiinae) from three distant geographical regions
Authors: Renault D , Vernon P , Vannier G
Published: September 2004

We compared the freezing susceptibility of three populations of Gnorimus variabilis (L., 1758) (Coleoptera: Cetoniidae) sampled from three distant locations in France. To separate the effects of habitat quality from those of genetics, we reared imagos from all field populations in a common garden experiment until the emergence of the third-instar larvae. The local climate appeared to determine the cold hardiness of the third-instar larvae, which live exclusively in cold seasons. The geographical location had an effect on the frost resistance (supercooling point) of the third-instar larvae of G. variabilis. We found no significant differences between the supercooling points of the populations originating from separate latitudes but from the same longitude, Sare (–10.9 ± 4.1 °C) and Husson (–11.5 ± 3.8 °C). Nonetheless, significant differences occurred between the larvae originating from the same northern latitude but from separate longitudes, Husson and La Robertsau (–17.8 ± 2.9 °C). It is the first time that a highly significant difference in the supercooling point of one stage within a single species has been observed along geographical gradients. Moreover, 19 of the 24 larvae originating from La Robertsau were alive after they were kept for 22 h at –10 °C compared with only 7 of the 24 larvae originating from Sare. When the three populations were reared in the laboratory under the same experimental conditions, the differential cryoresistance was preserved. It is likely that the greater freezing resistance found in the third-instar larvae of G. variabilis from La Robertsau could have a genetic component.
Modeled climate change effects on distributions of Canadian butterfly species
Authors: Peterson A Townsend , Martínez-Meyer Enrique , González-Salazar Constantino , Hall Peter W
Published: September 2004

Climate change effects on biodiversity are being documented now frequently in the form of changes in phenology and distributional shifts. However, the form that these effects will take over a longer timespan is unclear; for this understanding, a quantitative, validated, predictive approach is key. Here, we use ecological niche modeling and general circulation model outputs to estimate future potential geographic distributions of 111 Canadian butterfly species. We develop future estimates under two emission scenarios from each of two climate change modeling centers; future projections for biodiversity are not only scenario dependent (more severe emission scenarios produce more severe effects on species' distributions) but also model dependent (the Canadian Centre for Climate Modelling and Analysis results were more severe than the Hadley Centre results). One interesting feature is the appearance of disjunctions in species' distributions, hence creating "vicariant events" over very short time periods. In general, however, a cost of 1%–3% additional loss of species' distributions is associated with more severe scenarios of emissions and climate change, suggesting that subtle biodiversity consequences are associated with the different climate futures debated in political circles.
Trade-offs in the choice of refuges by common wall lizards: do thermal costs affect preferences for predator-free refuges?
Authors: Amo Luisa , López Pilar , Martín José
Published: September 2004

Prey often respond to predator presence by increasing refuge use. However, some types of refuges may expose prey to other types of predators. In addition, in selecting refuges ectothermic animals may have a conflict between safety and thermal suitability. In this paper we examined in the laboratory whether common wall lizards, Podarcis muralis (Laurenti, 1768), (i) prefer to use warm refuges to cold ones, (ii) prefer safe refuges to those with chemical cues of a saurophagous snake, and (iii) whether lizards face a trade-off between using a warm but snake-scented refuge or a cold but odorless one. Results did not show differences in refuge use in relation to refuge temperature, because common wall lizards only entered to investigate it, but they were not forced to hide. So, common wall lizards did not have to be at suboptimal temperatures for longer times. Common wall lizards avoided the use of predator-scented refuges, regardless of thermal conditions, and they also increased their movement rate, trying to escape from the terrarium. Because snakes are inconspicuous inside refuges, an avoidance response to their chemicals may enhance the survival possibilities of common wall lizards. We conclude that in common wall lizards, predation-risk costs are more important than thermal costs in determining refuge use.
The effects of crayfish predation on phenotypic and life-history variation in fathead minnows
Authors: Kusch R C , Chivers D P
Published: September 2004

Ecological theory predicts that the timing of the transition between life-history stages should vary with the costs and benefits associated with each stage. For example, the timing of hatching or metamorphosis may vary with the predation risk in each stage. Predator-induced changes in hatching time are well documented in some taxa but have not been reported in fishes. We provide the first empirical evidence that a species of fish can alter its hatching time in response to predator cues. We showed that fathead minnows, Pimephales promelas Rafinesque, 1820, exposed to chemical cues from virile crayfish, Orconectes virilis (Hagen, 1870), foraging on minnow embryos hatch sooner than those exposed to a blank control. Moreover, in the presence of cues from virile crayfish feeding on minnow embryos, the hatchlings exhibited a change in morphology because they had significantly shorter total lengths. There was a significant positive correlation between hatchling size and length of the developmental period, except in the high predation threat treatment. By hatching earlier, the fathead minnows escaped predation from virile crayfish that were actively foraging on fathead minnow eggs. Hatching at a smaller size, however, may make the fry more vulnerable to other predators.
Hydrodynamic and phylogenetic aspects of the adipose fin in fishes
Authors: Reimchen T E , Temple N F
Published: September 2004

The adipose fin on fishes is a highly conserved and enigmatic, small, non-rayed fin that has persisted from the Mesozoic on some basal teleosts such as salmonids. Using juvenile steelhead, Oncorhynchus mykiss (Walbaum, 1792), ranging from 5 to 18 cm standard length, we experimentally test the effects of adipose fin removal on swimming performance in a variable velocity flow chamber and quantify, with seven independent trials, amplitude and frequency of caudal fin movement at multiple flow velocities (range 10–39 cm·s–1). Results demonstrate that adipose fin removal on smolts produces an average 8% (range –3% to 23%) increase in caudal fin amplitude relative to unclipped fish across all velocities. However, we observed no effects in trials with smaller fish (<7 cm) or larger fish (>12 cm). Consistent with speculations in the literature, our results show that the adipose fin may function to control vortices enveloping the caudal fin during swimming or, alternatively, function as a passive precaudal sensor of turbulent flow. Phylogenetic persistence of this trait among multiple groups of early bony fishes is probably due to its hydrodynamic attributes rather than developmental constraints, and the current widespread practice in fisheries of removing the adipose fin as a marking technique may have significant biological costs.
Egg size predicts motor performance and postnatal weight gain of Australian Brush-turkey (Alectura lathami) hatchlings
Authors: Göth Ann , Evans Christopher S
Published: September 2004

Birds usually influence offspring survival through the amount of parental care they provide. Megapodes have evolved a different life history. Eggs are incubated by external heat sources, and chicks dig themselves out of their underground nest and live independently of their parents. Egg size is one of the few means by which females can influence chick survival. We found that in the Australian Brush-turkey, Alectura lathami Gray, 1831, eggs and hatchlings varied considerably in size, with a ratio of 1.62 between the largest and the smallest egg. Egg size was positively correlated with hatchling body mass and tarsus length. It also significantly predicted the chicks' motor performance: chicks from larger eggs dug their way out of their underground nest faster and were more active when kept in a resting box and monitored by motion detection software. The main advantage of reaching the surface more quickly is likely that such chicks will have more time to find suitable food, refuge, and a tree for roosting at night while still feeding on their internal yolk reserves. Egg size also interacted significantly with body mass during the first 10 months of life. A size advantage at hatching thus seems to have an immediate effect on motor performance and a longer term effect on the ability to gain mass.
CONNECTED EQUI-LENGTH LINE SEGMENTS FOR CURVE AND STRUCTURE MATCHING
Authors: ZHAO YU , CHEN YAN QIU
Published: September 2004

This paper deals with the problem of matching curves and structures extracted from 2D images that are subject to translation, rotation, scaling and other geometric transformations. We present in this paper a novel approach, Connected Equi-Length Line Segments (CELLS), for curve representation and matching. In our framework, a curve is represented by a number of connected equi-length line segments and a new matrix called Orientation Difference Matrix (ODM) is constructed for the curve, which reflects the distribution of the rest of the line segments with respect to the current one using orientation differences between them. The representation is invariant to rotation, scaling and translation. The problem of structure matching is also considered in this paper and is solved based on CELLS. The matching of structures is performed by (1) detecting tri-junctions and quad-junctions on the structures, (2) representing each arch using CELLS. A practical use of the proposed approach is demonstrated by registering a SAR image of a certain area to a map.
FROM PIXELS TO TRUE XML STRUCTURES IN DIGITAL DOCUMENT IMAGES
Authors: MA MATTHEW Y. , GUO JINHONG K. , WANG PATRICK S. P.
Published: September 2004

XML has been widely used as metadata for image retrieval. As a standard, it makes it easier to index and retrieve information across different platforms. However, how to automatically convert an image into XML format remains a challenge. In this paper, a system for generating structured document in XML from digitally captured document images is presented. The system is aimed at providing an easy to use tool for average users without requiring depth of knowledge in the document processing areas. Further, a XML/XSL generator is developed to accurately represent a document in a XML structure, yet in a representation that reflects its original layout.
A TWO-STAGE SYNERGETIC APPROACH FOR FACE RECOGNITION
Authors: CHEN WEIGANG , QI FEIHU , WANG ZHAOZHONG
Published: September 2004

A two-stage face recognition method is presented in this paper. In the first stage, the set of candidate patterns is narrowed down with the global similarity being taken into account. In the second stage, synergetic approach is employed to perform further recognition. Face image is segmented into meaningful regions, each of which is represented as a prototype vector. The similarity between a given region of the test pattern and a stored sample is obtained as the order parameter which serves as an element of the order vector. Finally, a modified definition of the potential function is given, and the dynamic model of recognition is derived from it. The effectiveness of the proposed method is experimentally confirmed.
Suppression of Visually and Memory-Guided Saccades Induced by Electrical Stimulation of the Monkey Frontal Eye Field. II. Suppression of Bilateral Saccades
Authors: Izawa Yoshiko , Suzuki Hisao , Shinoda Yoshikazu
Published: September 2004

To understand the neural mechanism of fixation, we investigated effects of electrical stimulation of the frontal eye field (FEF) and its vicinity on visually guided (Vsacs) and memory-guided saccades (Msacs) in trained monkeys and found that there were two types of suppression induced by the electrical stimulation: suppression of ipsilateral saccades and suppression of bilateral saccades. In this report, we characterized the properties of the suppression of bilateral Vsacs and Msacs. Stimulation of the bilateral suppression sites suppressed the initiation of both Vsacs and Msacs in all directions during and ∼50 ms after stimulation but did not affect the vector of these saccades. The suppression was stronger for ipsiversive larger saccades and contraversive smaller saccades, and saccades with initial eye positions shifted more in the saccadic direction. The most effective stimulation timing for the suppression of ipsilateral and contralateral Vsacs was ∼40–50 ms before saccade onset, indicating that the suppression occurred most likely in the superior colliculus and/or the paramedian pontine reticular formation. Suppression sites of bilateral saccades were located in the prearcuate gyrus facing the inferior arcuate sulcus where stimulation induced suppression at ≤40 μA but usually did not evoke any saccades at 80 μA and were different from those of ipsilateral saccades where stimulation evoked saccades at ≤50 μA. The bilateral suppression sites contained fixation neurons. The results suggest that fixation neurons in the bilateral suppression area of the FEF may play roles in maintaining fixation by suppressing saccades in all directions.
Synaptic Inputs to Trigeminal Primary Afferent Neurons Cause Firing and Modulate Intrinsic Oscillatory Activity
Authors: Verdier Dorly , Lund James P. , Kolta Arlette
Published: September 2004

In this paper, we investigated the influence of synapses on the cell bodies of trigeminal muscle spindle afferents that lie in the trigeminal mesencephalic nucleus (NVmes), using intracellular recordings in brain stem slices of young rats. Three types of synaptic responses could be evoked by electrical stimulation of the adjacent supratrigeminal, motor, and main sensory nuclei and the intertrigeminal area: monophasic depolarizing postsynaptic potentials (PSPs), biphasic PSPs, and all or none action potentials without underlying excitatory PSPs (EPSPs). Many PSPs and spikes were abolished by bath-application of 6,7-dinitroquinoxaline (DNQX) alone or combined with d,l-2-amino-5-phosphonovaleric acid (APV), suggesting that they are mediated by non– N-methyl-d-aspartate (NMDA) and NMDA glutamatergic receptors, while some action potentials were sensitive to bicuculline, indicating involvement of GABAA receptors. A number of cells showed spontaneous membrane potential oscillations, and stimulation of synaptic inputs increased the amplitude of the oscillations for several cycles, which often triggered repetitive firing. Furthermore, the oscillatory rhythm was reset by the stimulation. Our results show that synaptic inputs to muscle primary afferent neurons in NVmes from neighboring areas are mainly excitatory and that they cause firing. In addition, the inputs synchronize intrinsic oscillations, which may lead to sustained, synchronous firing in a subpopulation of afferents. This may be of importance during rapid biting and during the mastication of very hard or tough foods.
Transfer of Motor Performance in an Obstacle Avoidance Task to Different Walking Conditions
Authors: Lam Tania , Dietz Volker
Published: September 2004

The aim of this study was to examine whether subjects who have learned a skilled locomotor task can transfer the acquired performance to conditions involving either a change in the external coordinates or in the sensory input from one leg. Subjects were trained to step over an obstacle with minimal foot clearance without visual information about either the obstacle or their legs during treadmill walking. Leg muscle activity and joint kinematics were recorded and analyzed. Acoustic signals provided feedback about foot clearance over the obstacle. After successful training, the transfer of learning between level and downhill walking and to walking with additional weight attached to the leg was examined. It was found that once subjects learned to step over the obstacle at an optimal foot clearance, they could transfer their performance within the first step over the obstacle in the new walking conditions. Closer examination of the transfer between level and downhill walking revealed no consistent kinematic strategy across subjects. To transfer the learned performance to walking with additional weight, subjects consistently and automatically increased biceps femoris muscle activation. The results are discussed in the context of emerging concepts in the neural control of walking and motor learning.
Changing Brain Networks for Visuomotor Control With Increased Movement Automaticity
Authors: Floyer-Lea A. , Matthews P. M.
Published: September 2004

Learning a motor skill is associated with changes in patterns of brain activation with movement. Here we have further characterized these dynamics during fast (short-term) learning of a visuomotor skill using functional magnetic resonance imaging. Subjects ( n = 15) were studied as they learned to visually track a moving target by varying the isometric force applied to a pressure plate held in the right hand. Learning was confirmed by demonstration of improved performance and automaticity (the relative lack of need for conscious attention during task execution). We identified two distinct, time-dependent patterns of functional changes in the brain associated with these behavioral changes. An initial, more attentionally demanding stage of learning was associated with the greatest relative activity in widely distributed, predominantly cortical regions including prefrontal, bilateral sensorimotor, and parietal cortices. The caudate nucleus and ipsilateral cerebellar hemisphere also showed significant activity. Over time, as performance improved, activity in these regions progressively decreased. There was an increase in activity in subcortical motor regions including that of the cerebellar dentate and the thalamus and putamen. Short-term motor-skill learning thus is associated with a progressive reduction of widely distributed activations in cortical regions responsible for executive functions, processing somatosensory feedback and motor planning. The results suggest that early performance gains rely strongly on prefrontal-caudate interactions with later increased activity in a subcortical circuit involving the cerebellum and basal ganglia as the task becomes more automatic. Characterization of these changes provides a potential tool for functional “dissection” of pathologies of movement and motor learning.
Deciphering the Renal Code: Advances in Conditional Gene Targeting
Authors: Gawlik Alexander , Quaggin Susan E.
Published: September 2004

Several powerful new techniques can examine gene function in mammals. Recombinase systems and kidney-specific promoters enable gene knockout and overexpression. Genetic systems induced on administration or removal of antibiotics or hormones permit control of gene expression. Gene silencing using short interfering RNA expression systems should accelerate loss-of-function studies. Thorough characterization of animals that have undergone conditional gene targeting has already provided insights into renal development and diseases. Here we discuss the advantages and pitfalls of currently available gene-targeting systems.
Why Calcium-Stimulated Adenylyl Cyclases?
Authors: Ferguson Gregory D. , Storm Daniel R.
Published: September 2004

The Ca2+/calmodulin-stimulated adenylyl cyclases, AC1 and AC8, play a critical role in several forms of neuroplasticity, including long-lasting long-term potentiation (L-LTP) and long-term memory (LTM). By coupling neuronal activity and Ca2+increases to the production of cAMP, AC1 and AC8 activate cAMP-dependent signal transduction and transcriptional pathways critical for L-LTP and LTM.
A Hypothesis About the Role of Adult Neurogenesis in Hippocampal Function
Authors: Schinder Alejandro F. , Gage Fred H.
Published: September 2004

The functional relevance of adult hippocampal neurogenesis has long been a matter of intense experimentation and debate, but the precise role of new neurons has not been sufficiently elaborated. Here we propose a hypothesis in which specific features of newly generated neurons contribute to hippocampal plasticity and function and discuss the most recent and relevant findings in the context of the proposed hypothesis.
The Architecture of the Active Zone in the Presynaptic Nerve Terminal
Authors: Zhai R. Grace , Bellen Hugo J.
Published: September 2004

Active zones are highly specialized sites for release of neurotransmitter from presynaptic nerve terminals. The architecture of the active zone is exquisitely designed to facilitate the regulated tethering, docking, and fusing of the synaptic vesicles with the plasma membrane. Here we present our view of the structural and molecular organization of active zones across species and propose that all active zones are organized according to a common principle in which the structural differences correlate with the kinetics of transmitter release.
First Encounter: How Pathogens Compromise Epithelial Transport
Authors: Kunzelmann Karl , McMorran Brendan
Published: September 2004

Pathogenic organisms trigger numerous signaling pathways that ultimately lead to drastic changes in physiological functions. Apart from altering structure and function of the epithelial tight junction barrier and activating inflammatory cascades, they induce changes in fluid and electrolyte transport. Pathogens do so by activating or by inhibiting ion channels and transporters, and the result might be to their benefit or to their disadvantage.
A Two-Holed Story: Structural Secrets About ClC Proteins Become Unraveled?
Authors: Babini Elena , Pusch Michael
Published: September 2004

ClC Cl− channels are found in almost all organisms, ranging from bacteria to mammals, in which nine Cl− channels belonging to the ClC family have been identified. The biophysical properties and physiological functions of ClC Cl− channels have been extensively reviewed. In this short review, we will focus on recent results obtained on the X-ray structure and functional properties of the prokaryotic ClC-ec1 protein and some results obtained on the role of the cytoplasmic COOH terminus of mammalian ClCs.
The Nuclear Envelope and Human Disease
Authors: Muchir Antoine , Worman Howard J.
Published: September 2004

Mutations in nuclear lamins A and C, intermediate filament proteins of the nuclear envelope, cause diseases affecting various tissues and the aging process. We review what is known about nuclear lamin function and the different diseases caused by mutations in lamins A and C and associated inner nuclear membrane proteins.
Paxillin: Adapting to Change
Authors: Brown Michael C. , Turner Christopher E.
Published: September 2004

Molecular scaffold or adaptor proteins facilitate precise spatiotemporal regulation and integration of multiple signaling pathways to effect the optimal cellular response to changes in the immediate environment. Paxillin is a multidomain adaptor that recruits both structural and signaling molecules to focal adhesions, sites of integrin engagement with the extracellular matrix, where it performs a critical role in transducing adhesion and growth factor signals to elicit changes in cell migration and gene expression.
Genetic Models of Mechanotransduction: The NematodeCaenorhabditis elegans
Authors: Syntichaki Popi , Tavernarakis Nektarios
Published: September 2004

Mechanotransduction, the conversion of a mechanical stimulus into a biological response, constitutes the basis for a plethora of fundamental biological processes such as the senses of touch, balance, and hearing and contributes critically to development and homeostasis in all organisms. Despite this profound importance in biology, we know remarkably little about how mechanical input forces delivered to a cell are interpreted to an extensive repertoire of output physiological responses. Recent, elegant genetic and electrophysiological studies have shown that specialized macromolecular complexes, encompassing mechanically gated ion channels, play a central role in the transformation of mechanical forces into a cellular signal, which takes place in mechanosensory organs of diverse organisms. These complexes are highly efficient sensors, closely entangled with their surrounding environment. Such association appears essential for proper channel gating and provides proximity of the mechanosensory apparatus to the source of triggering mechanical energy. Genetic and molecular evidence collected in model organisms such as the nematode worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the mouse highlight two distinct classes of mechanically gated ion channels: the degenerin (DEG)/epithelial Na+channel (ENaC) family and the transient receptor potential (TRP) family of ion channels. In addition to the core channel proteins, several other potentially interacting molecules have in some cases been identified, which are likely parts of the mechanotransducing apparatus. Based on cumulative data, a model of the sensory mechanotransducer has emerged that encompasses our current understanding of the process and fulfills the structural requirements dictated by its dedicated function. It remains to be seen how general this model is and whether it will withstand the impiteous test of time.
Renal Vacuolar H+-ATPase
Authors: Wagner Carsten A. , Finberg Karin E. , Breton Sylvie , Marshansky Vladimir , Brown Dennis , Geibel John P.
Published: September 2004

Vacuolar H+-ATPases are ubiquitous multisubunit complexes mediating the ATP-dependent transport of protons. In addition to their role in acidifying the lumen of various intracellular organelles, vacuolar H+-ATPases fulfill special tasks in the kidney. Vacuolar H+-ATPases are expressed in the plasma membrane in the kidney almost along the entire length of the nephron with apical and/or basolateral localization patterns. In the proximal tubule, a high number of vacuolar H+-ATPases are also found in endosomes, which are acidified by the pump. In addition, vacuolar H+-ATPases contribute to proximal tubular bicarbonate reabsorption. The importance in final urinary acidification along the collecting system is highlighted by monogenic defects in two subunits (ATP6V0A4, ATP6V1B1) of the vacuolar H+-ATPase in patients with distal renal tubular acidosis. The activity of vacuolar H+-ATPases is tightly regulated by a variety of factors such as the acid-base or electrolyte status. This regulation is at least in part mediated by various hormones and protein-protein interactions between regulatory proteins and multiple subunits of the pump.
Role of Caveolae and Caveolins in Health and Disease
Authors: Cohen Alex W. , Hnasko Robert , Schubert William , Lisanti Michael P.
Published: September 2004

Although they were discovered more than 50 years ago, caveolae have remained enigmatic plasmalemmal organelles. With their characteristic “flasklike” shape and virtually ubiquitous tissue distribution, these interesting structures have been implicated in a wide range of cellular functions. Similar to clathrin-coated pits, caveolae function as macromolecular vesicular transporters, while their unique lipid composition classifies them as plasma membrane lipid rafts, structures enriched in a variety of signaling molecules. The caveolin proteins (caveolin-1, -2, and -3) serve as the structural components of caveolae, while also functioning as scaffolding proteins, capable of recruiting numerous signaling molecules to caveolae, as well as regulating their activity. That so many signaling molecules and signaling cascades are regulated by an interaction with the caveolins provides a paradigm by which numerous disease processes may be affected by ablation or mutation of these proteins. Indeed, studies in caveolin-deficient mice have implicated these structures in a host of human diseases, including diabetes, cancer, cardiovascular disease, atherosclerosis, pulmonary fibrosis, and a variety of degenerative muscular dystrophies. In this review, we provide an in depth summary regarding the mechanisms by which caveolae and caveolins participate in human disease processes.
Role of Oxidative Modifications in Atherosclerosis
Authors: Stocker Roland , Keaney John F.
Published: September 2004

This review focuses on the role of oxidative processes in atherosclerosis and its resultant cardiovascular events. There is now a consensus that atherosclerosis represents a state of heightened oxidative stress characterized by lipid and protein oxidation in the vascular wall. The oxidative modification hypothesis of atherosclerosis predicts that low-density lipoprotein (LDL) oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis. In support of this hypothesis, oxidized LDL can support foam cell formation in vitro, the lipid in human lesions is substantially oxidized, there is evidence for the presence of oxidized LDL in vivo, oxidized LDL has a number of potentially proatherogenic activities, and several structurally unrelated antioxidants inhibit atherosclerosis in animals. An emerging consensus also underscores the importance in vascular disease of oxidative events in addition to LDL oxidation. These include the production of reactive oxygen and nitrogen species by vascular cells, as well as oxidative modifications contributing to important clinical manifestations of coronary artery disease such as endothelial dysfunction and plaque disruption. Despite these abundant data however, fundamental problems remain with implicating oxidative modification as a (requisite) pathophysiologically important cause for atherosclerosis. These include the poor performance of antioxidant strategies in limiting either atherosclerosis or cardiovascular events from atherosclerosis, and observations in animals that suggest dissociation between atherosclerosis and lipoprotein oxidation. Indeed, it remains to be established that oxidative events are a cause rather than an injurious response to atherogenesis. In this context, inflammation needs to be considered as a primary process of atherosclerosis, and oxidative stress as a secondary event. To address this issue, we have proposed an “oxidative response to inflammation” model as a means of reconciling the response-to-injury and oxidative modification hypotheses of atherosclerosis.
Periostin as a Novel Factor Responsible for Ventricular Dilation
Authors: Katsuragi Naruto , Morishita Ryuichi , Nakamura Noriko , Ochiai Tayehito , Taniyama Yoshiaki , Hasegawa Yasuhiro , Kawashima Kayoko , Kaneda Yasufumi , Ogihara Toshio , Sugimura Keijiro
Published: September 2004

Background—

Periostin is highly expressed in the myocardium in patients with heart failure. However, no report has documented the function of periostin. To identify the function of periostin in the pathophysiology of heart failure, overexpression or loss of function of the periostin gene was examined by direct transfection into the rat heart.

Methods and Results—

Rats transfected with the periostin gene by the HVJ-liposome method showed left ventricular (LV) dilation as assessed by echocardiography, accompanied by an increase in periostin expression. Consistently significant differences were observed in LV pressure, LV end-diastolic pressure, LV
dP
/
dt
max
, and LV
dP
/
dt
min
at 6 and 12 weeks after transfection in rats transfected with the periostin gene, accompanied by a decrease in cardiac myocytes and an increase in collagen deposition. Importantly, periostin has the ability to inhibit the spreading of myocytes and the adhesion of cardiac fibroblasts with or without fibronectin. Markers of cardiac dysfunction such as brain natriuretic peptide and endothelin-1 gene expression were significantly increased after transfection in the LV of rats transfected with the periostin gene. These data demonstrate that overexpression of the periostin gene led to cardiac dysfunction. Thus, we examined the inhibition of periostin in Dahl salt-sensitive rats by an antisense strategy because periostin is highly expressed in heart failure. Importantly, inhibition of periostin gene expression resulted in a significant increase in survival rate, accompanied by an improvement of LV function.

Conclusion—

The present study demonstrates the contribution of the periostin gene to cardiac dilation in animal models. Inhibition of periostin might become a new therapeutic target for the treatment of heart failure.