bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of soil type on burrowing behavior and cocoon formation in the green-striped burrowing frog,Cyclorana alboguttata
Authors: Booth D.T.
Published: August 2006

This study examined the effect of soil type on burrowing behaviour and cocoon formation during aestivation in the green-striped burrowing frog, Cyclorana alboguttata (Günther, 1867). Given a choice, frogs always chose to burrow in wet sand in preference to wet clay. Frogs buried themselves faster and dug deeper burrows in sandy soil. However, under my laboratory conditions, there was little difference in the pattern of soil drying between the two soil types. Frogs in both sand and clay soil experienced hydrating conditions for the first 3 months and dehydrating conditions for the last 3 months of the 6-month aestivation period, and cocoons were not formed until after 3 months of aestivation. After 6 months, there were more layers in the cocoons of frogs aestivating in sand than those aestivating in clay. Frogs were able to absorb water from sandy soil with water potentials greater than –400 kPa, but lost water when placed on sand with a water potential of –1000 kPa.
Influence of nest location and yolkless eggs on the hatching success of leatherback turtle clutches in French Guiana
Authors: Caut Stéphane , Guirlet Elodie , Jouquet Pascal , Girondot Marc
Published: August 2006

The hatching success of leatherback turtles, Dermochelys coriacea (Vandelli, 1761), is influenced by heterogeneously distributed ecological factors. However, the hatching success according to nest-site selection has rarely been studied and little is known about the role of nest-site selection and infertile (yolkless) egg production on the predation rate and development of fertile eggs in leatherback turtle nests laid in French Guiana. A field study of 99 leatherback turtle nests was conducted to quantify the relationships between hatching success and (i) the nest-site selection (i.e., vegetation line, sea tide line) and (ii) the infertile eggs, especially their state after incubation (i.e., hydrated or dehydrated) and their effects on predation rate. We found that hatching success on this beach was very low (38.2%). This study illustrates that nest-site selection influences the predation rate and the dehydration of yolkless eggs, while the production of yolkless eggs by leatherback turtles has consequences on nest success. The proportion of yolkless eggs in the clutch, as well as their status at the end of incubation (hydrated or not, preyed upon), correlates with predation rate, development of yolked eggs, and hatching success. There was a significant relationship between nest location (relative to high tide line and vegetation line) and both the predation rates of eggs and the percentage of dehydrated yolkless eggs within a clutch. The production of yolkless eggs was related to hatching success and supports the hypothesis that yolkless eggs have a positive effect on the future of the clutch.
Singing in the shade: song and song posts of northern cardinals near nesting Cooper’s hawks
Authors: Duncan William J. , Bednekoff Peter A.
Published: August 2006

Animals may compensate for increased predation risk by changing the behaviours that make them vulnerable. In this study, we compared the singing and perching behaviours of northern cardinals ( Cardinalis cardinalis L., 1758) living within 100 m of nesting Cooper’s hawks ( Accipiter cooperii (Bonaparte, 1828)) with that of cardinals in similar control sites. Cardinals sang similar amounts at hawk nests and at control sites, but they sang from less exposed perches when near Cooper’s hawk nests. These results suggest that singing from an exposed perch is both more dangerous and more effective for northern cardinals.
Combining stable isotope and intestinal parasite information to evaluate dietary differences between individual ringed seals (Phoca hispida botnica)
Authors: Sinisalo Tuula , Valtonen E. Tellervo , Helle Eero , Jones Roger I.
Published: August 2006

The diet and foraging behaviour of nine individual Baltic ringed seals ( Phoca hispida botnica Gmelin, 1785) in the Bothnian Bay were studied by combining results from stable isotope analyses (δ13C and δ15N) with data on intestinal parasites whose occurrence varied among the fish hosts. The patterns of infection with three acanthocephalan parasites, Corynosoma semerme (Forssell, 1904), Corynosoma magdaleni Montreuil, 1958, and Corynosoma strumosum (Rudolphi, 1802), and with a cestode larva, Schistocephalus solidus (Müller, 1776), were examined. The ringed seals become infected with these intestinal parasites by feeding on the fish hosts and hence have different parasite species and different parasite burdens according to their dietary history. δ13C and δ15N values were determined from diaphragm muscle of the seals and from tissues of potential prey items. A dual isotope plot of δ13C and δ15N values for individual seals and mean values for key potential prey species, together with the parasitological data from the seals, allowed inferences to be drawn about the feeding of individual seals. It appeared that two seals foraged particularly on fourhorn sculpin ( Myoxocephalus quadricornis (L., 1758)) and one seal consumed a high proportion of the isopod Saduria entomon (L., 1758). Three seals apparently preferred coastal benthic prey in their diets, while two other seals fed more on pelagic herring ( Clupea harengus membras L., 1761). One older female seal evidently also fed on salmon ( Salmo salar L., 1758).
What drives variation in habitat use by Anolis lizards: habitat availability or selectivity?
Authors: Johnson M.A. , Kirby R. , Wang S. , Losos J.B.
Published: August 2006

Geographic variation in habitat availability may drive geographic variation in a species’ habitat use; alternatively, species adapted to particular habitat characteristics may use a habitat regardless of its availability within an environment. In this study, we investigated habitat use of two sympatric species of Anolis lizards that are morphologically specialized to use different microhabitats. We examined variation in microhabitat use and availability among four distinct forest types. In each forest type, we quantified available microhabitats (i.e., perch diameter, angle of inclination, and visibility), as well as microhabitats actually used by each species. We found that species consistently differed in microhabitat use, corresponding to each species’ morphological specializations. However, microhabitat use of both species varied among sites. This variation in Anolis gundlachi Peters, 1876 reflected differences in microhabitat availability, while the variation in Anolis krugi Peters, 1876 resulted from differential microhabitat selectivity. These results indicate that both habitat availability and habitat preferences must be examined in multiple localities for a species to understand the causes of variation in its habitat use.
Effect of dietary cues on kin discrimination of juvenile Atlantic salmon (Salmo salar) and brook trout (Salvelinus fontinalis)
Authors: Rajakaruna R.S. , Brown J.A.
Published: August 2006

Several salmonid species can discriminate kin from non-kin using recognition cues. These are known to involve both genetic and environmental components. This study examined the effect of diet, an environmental cue, on kin discrimination in juvenile Atlantic salmon ( Salmo salar L., 1758) and brook trout ( Salvelinus fontinalis (Mitchill, 1814)). Juveniles were reared in kin and non-kin groups. Three different diets were fed to three kin groups and three non-kin groups. Juveniles were then tested for their ability to discriminate kin. We found that juveniles discriminated individuals between kin and non-kin when they shared a common diet with kin, but did not do so when kin were fed a different diet. Moreover, we predicted that diet and genotype together would provide stronger cues than sharing either dietary cues or genetic cues. When the juveniles were given a choice between kin fed the same diet and kin fed a different diet, they did not show a consistent preference for the former. However, in the absence of kinship, juveniles preferred cues from a common diet, i.e., they preferred cue water conditioned by non-kin sharing a common diet than cue water from non-kin fed a different diet. Our results show that dietary cues affect kin discrimination in juvenile Atlantic salmon and brook trout and provide the first empirical evidence for the influence of diet on kin discrimination in salmonids. The functional explanation of these results is that the preferences in kin discrimination are likely context dependent.
Orientation-cage experiments with the European Quail during the breeding season and autumn migration
Authors: Rodríguez-Teijeiro J.D. , Barroso A. , Gallego S. , Puigcerver M. , Vinyoles D.
Published: August 2006

The directional movements of the male European Quail, Coturnix coturnix (L., 1758), during the breeding season and autumn migration were studied using Emlen orientation cages. The characteristics and evolution of the habitat in which males were captured and the sexual behaviour shown at capture indicate that these birds move in search of mating partners rather than of suitable habitats. These displacements are known as “gypsy movements” but are better described, as argued in this paper, as “movements in search of females”. A majority of caged birds (59%) showed a preferred direction (α = 238.5°), which coincided almost exactly with that observed in recoveries of ringed birds during autumn migration (α = 251.3°) but not with results from cage experiments during the same migratory period (α = 187.8°). Therefore, we conclude that displacements of the male European Quail, as shown in ringing recoveries, are much more influenced by “movements in search of females” than by migration. These movements are clearly towards the southwest, the males taking short flights towards suitable breeding grounds and driven by river-course habitats. In addition, we confirm that Emlen funnels are suitable for controlled experiments on the orientation of males in demes of European Quail.
Is the perception of their own odour effective in orienting the exploratory activity of cave fishes?
Authors: Paglianti Annalisa , Messana Giuseppe , Cianfanelli Alessandro , Berti Roberto
Published: August 2006

Spatial knowledge of the surrounding environment is extremely important for animals to locate and efficiently exploit available resources (e.g., food, shelters, mates). Fishes usually acquire spatial information about their home range through vision, but vision fails in the dark and other sensory pathways have to be exploited. Fishes possess a remarkable olfactory system and have evolved a refined ability of chemical detection and recognition. Nevertheless, while the role of chemical cues in spatial orientation is well known in long-distance salmonid migrations, it has never been investigated in orientation within local, familiar areas. Here we report the first evidence that fish swimming can be topographically polarized by self-odour perception. When an unfamiliar area was experimentally scented with fish self-odour, the cave cyprinid Phreatichthys andruzzii Vinciguerra, 1924 behaved as if the area was previously explored. The fish preferred an odour-free area to a self-odour-scented one, and when offered the choice between a familiar and an unfamiliar area, they preferred the unexplored environment. Avoidance of self-odour-scented areas would allow effective exploration of the subterranean environment, minimizing the risks of repeatedly exploring the same water volumes. Our results are the first clear evidence that fish can use their own odour to orient their locomotor activity when visual cues are not available. This highlights the possible role of chemical information in fish orientation.
Effect of exposure to short-term heat stress on survival and fecundity in Drosophila ananassae
Authors: Sisodia Seema , Singh Bashisth N.
Published: August 2006

In ectothermic organisms, temperature plays a vital role in survival and reproductive success. Founding isofemale lines from wild-collected females is a basic tool for characterizing quantitative traits in a natural population. The effects of heat shock, i.e., short exposure to heat stress, on survival and reproductive success in 10 recently collected isofemale lines of Drosophila ananassae Doleschall, 1858 were compared. Flies were treated as follows: (i) unstressed control; (ii) placed at 37 °C for 90 min (pre-treatment); (iii) placed at 40 °C for 60 min 24 h before the fecundity test; and (iv) placed at 40 °C for 60 min with pre-treatment 16 h before they were exposed to 40 °C. The heat stress strongly affected survival. However, there was no significant difference between the survival of males and females. Furthermore, the female fecundity, measured as F1 offspring produced over the next 12 days, was also reduced. Heat pre-treatment improved survival of both male and female and also improved female productivity. We found significant variation in female fecundity among isofemale lines, and intraclass correlations increased for stress treatments. The results suggest that a small increase in environmental stress may affect fitness traits, and there is enough genetic variation for thermal adaptation in D. ananassae.
FORWARD-RATE VOLATILITIES AND THE SWAPTION MATRIX: WHY NEITHER TIME-HOMOGENEITY NOR TIME-DEPENDENCE ARE ENOUGH
Authors: REBONATO RICCARDO
Published: August 2006

This work presents the first systematic analysis of the whole swaption matrix by fitting a parsimonious, nonlinear, financially-inspired volatility model to market data. The study uses several years of data spanning period of major market volatility. We find that the quality of the fits is good (on average of the same magnitude as the bid-offer spread), and better when a displaced-diffusion approach is chosen, but some systematic shortcomings are observed and discussed. The analysis suggests that a two-regime Markov chain approach may be more successful and better financially motivated.

More generally, the present study highlights the shortcomings of purely time-dependent or time-homogenous approaches. These findings should be applicable to other option markets as well.

Finally, we find that the present (nonlinear) model vastly outperforms PCA-based approaches when in comes to predicting moves in implied volatilities.
ANALYTICAL MODELING AND SIMULATION OF PHASE NOISE IN BISTATIC SYNTHETIC APERTURE RADAR SYSTEMS
Authors: WANG WENQIN
Published: August 2006

The requirement of phase noise imposed on the stable local oscillator for bistatic synthetic aperture radar (SAR) is much more severe than in the monostatic cases. So accurate phase noise simulation is of great importance during the design and development of bistatic SAR systems. This letter concentrates on the impacts of limited oscillator stability between bistatic transmitter and receiver, and presents an analytical model of phase noise that solves some drawbacks implicitly present in the previously proposed models. This model uses the Gaussian noise as the input of a hypothetical low-pass filter and its output is then considered as phase noise. Finally, some simulation results are provided to demonstrate the validity of this model.
International student exchange and the medical curriculum: evaluation of a medical sciences translational physiology course in Brazil
Authors: Morris Mariana , Jones T. David , Rocha Maria Jose Alves , Fazan Rubens , Chapleau Mark W. , Salgado Helio C. , Johnson Alan Kim , Irigoyen Maria Claudia , Michelini Lisete C. , Goldstein David L.
Published: August 2006

The objective of the present study was to conduct a short-term international course on translational physiology for medical students from Wright State University and the University of Iowa. The goals were to 1) provide students with an exposure to the academic, cultural, and medical environments in Brazil; 2) promote awareness of the global medical community; and 3) provide an academic course focused on translational physiology. An evaluation of the students was conducted to determine whether such a short-term course might be useful in the medical curriculum. The 2-wk course was held in the summer of 2005 at the University of São Paulo School of Medicine in Ribeirão Preto, Brazil, for 23 American students. The program included presentations of basic and clinical topics, meetings with medical students, and clinical presentations. The program finished with student attendance at a scientific meeting sponsored by the Brazilian Society of Hypertension. Student surveys evaluated issues related to perceived treatment, Brazilian medical school environment, culture and personal attributes, and career aspirations. The international Medical Sciences Translational Physiology course for medical students provided a brief, but intense, experience. It gave students a picture of the medical environment in Brazil and an appreciation for the differences and similarities in cultures. Most students reported that it was a positive experience that would be beneficial to their careers. In conclusion, a short-term international course provides an efficient means for medical students to experience aspects of global medical science.
Pancreatic islet function in ω-3 fatty acid-depleted rats: alteration of calcium fluxes and calcium-dependent insulin release
Authors: Zhang Y. , Oguzhan B. , Louchami K. , Chardigny J.-M. , Portois L. , Carpentier Y. A. , Malaisse W. J. , Herchuelz A. , Sener A.
Published: August 2006

Considering the insufficient supply of long-chain polyunsaturated ω-3 fatty acids often prevailing in Western populations, this report deals mainly with alterations of Ca2+fluxes and Ca2+-dependent insulin secretory events in isolated pancreatic islets from ω-3-depleted rats. In terms of45Ca2+handling, the islets from ω-3-depleted rats, compared with those from normal animals, displayed an unaltered responsiveness to an increase in extracellular K+concentration, a lower inflow rate and lower fractional outflow rate of the divalent cation, and higher45Ca2+-labeled cellular pool(s) at isotopic equilibrium. The latter anomaly was corrected 120 min after intravenous injection of a novel medium-chain triglyceride-fish oil (MCT:FO) emulsion, distinct from a control ω-3-poor MCT-olive oil (MCT:OO) emulsion. At 8.3 mM d-glucose, insulin release was higher in islets from ω-3-depleted rats vs. control animals, coinciding with a higher cytosolic Ca2+concentration. The relative magnitude of the increase in insulin output attributable to a rise in d-glucose as well as extracellular Ca2+or K+concentration, to the absence vs. presence of verapamil and to the presence vs. absence of extracellular Ca2+, theophylline, phorbol 12-myristate 13-acetate, or Ba2+, was always more pronounced in islets from ω-3-depleted rats injected with the MCT:OO compared with the MCT:FO emulsion. A comparable situation prevailed when comparing islets from noninjected ω-3-depleted and normal rats. In light of these and previous findings, we propose that an impairment of Na+,K+-ATPase activity plays a major, although not an exclusive, role in the perturbation of Ca2+fluxes and Ca2+-dependent secretory events in the islets from ω-3-depleted rats.
Growth hormone-releasing hormone and corticotropin-releasing hormone enhance non-rapid-eye-movement sleep after sleep deprivation
Authors: Schüssler P. , Yassouridis A. , Uhr M. , Kluge M. , Weikel J. , Holsboer F. , Steiger A.
Published: August 2006

The neuropeptides growth hormone (GH)-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) regulate sleep and nocturnal hormone secretion in a reciprocal fashion, at least in males. GHRH promotes sleep and GH and inhibits hypothalamo-pituitary-adrenocortical (HPA) hormones. CRH exerts opposite effects. In women, a sexual dimorphism was found because GHRH impairs sleep and stimulates HPA hormones. Sleep deprivation (SD) is the most powerful stimulus for inducing sleep. Studies in rodents show a key role of GHRH in sleep promotion after SD. The effects of GHRH and CRH on sleep-endocrine activity during the recovery night after SD are unknown. We compared sleep EEG, GH, and cortisol secretion between nights before and after 40 h of SD in 48 normal women and men aged 19–67 yr. During the recovery night, GHRH, CRH, or placebo were injected repetitively. After placebo during the recovery night, non-rapid-eye-movement sleep (NREMS) and rapid-eye-movement sleep (REMS) increased and wakefulness decreased compared with the baseline night. After GHRH, the increase of NREMS and the decrease of wakefulness were more distinct than after placebo. Also, after CRH, NREMS increased higher than after placebo, and a positive correlation was found between age and the baseline-related increase of slow-wave sleep. REMS increased after placebo and after GHRH, but not after CRH. EEG spectral analysis showed increases in the lower frequencies and decreases in the higher frequencies during NREMS after each of the treatments. Cortisol and GH did not differ between baseline and recovery nights after placebo. After GHRH, GH increased and cortisol decreased. Cortisol increased after CRH. No sex differences were found in these changes. Our data suggest that GHRH and CRH augment NREMS promotion after SD. Marked differences appear to exist in peptidergic sleep regulation between spontaneous and recovery sleep.
Chronic hyperglycemia impairs functional vasodilation via increasing thromboxane-receptor-mediated vasoconstriction
Authors: Xiang Lusha , Naik Jay S. , Abram Sean R. , Hester Robert L.
Published: August 2006

Individuals with hyperglycemia exhibit impaired exercise performance and functional vasodilatory response. Based on the importance of arachidonic acid (AA) metabolites in functional vasodilation and the increased thromboxane-to-prostacyclin ratio in diabetes, we hypothesized that chronic hyperglycemia in diabetes increases thromboxane-receptor (TP)-mediated vasoconstriction, resulting in an attenuated functional vasodilation. Three groups of lean Zucker rats (8 wk) were used to test the effects of chronic hyperglycemia on endothelial function: normal, streptozotocin (STZ; 70 mg/kg ip), and STZ + insulin (2 U/day). After 4 wk of treatment, spinotrapezius arcade arterioles were chosen for microcirculatory observation. Arteriolar diameter was measured following muscle stimulation and 10 μM AA application in the absence and presence of 1 μM SQ-29548 (TP antagonist). STZ rats exhibited significantly higher fasting glucose levels and attenuated functional and AA-induced dilation compared with normal animals. SQ-29548 improved the vasodilatory responses in STZ rats but had no effect in controls. Insulin treatment normalized both the glucose levels and the vasodilatory responses, and SQ-29548 treatment had no effect on functional or AA-mediated vasodilation in STZ + insulin animals. These results suggest that the impaired functional vasodilation in diabetic rats is due to hyperglycemia-mediated increases in TP-mediated vasoconstriction.
Acute ascorbate supplementation alone or combined with arginase inhibition augments reflex cutaneous vasodilation in aged human skin
Authors: Holowatz Lacy A. , Thompson Caitlin S. , Kenney W. Larry
Published: August 2006

Full expression of reflex cutaneous vasodilation (VD) is dependent on nitric oxide (NO) and is attenuated in older humans. NO may be decreased by an age-related increase in reactive oxygen species or a decrease in l-arginine availability via upregulated arginase. The purpose of this study was to determine the effect of acute antioxidant supplementation alone and combined with arginase inhibition on reflex VD in aged skin. Eleven young (Y; 22 ± 1 yr) and 10 older (O; 68 ± 1 yr) human subjects were instrumented with four intradermal microdialysis (MD) fibers. MD sites were control (Co), NO synthase inhibited (NOS-I), l-ascorbate supplemented (Asc), and Asc + arginase-inhibited (Asc + A-I). After baseline measurements, subjects underwent whole body heating to increase oral temperature (Tor) by 0.8°C. Red blood cell flux was measured by using laser-Doppler flowmetry, and cutaneous vascular conductance (CVC) was calculated (CVC = flux/mean arterial pressure) and normalized to maximal (CVCmax). VD during heating was attenuated in O (Y: 37 ± 3 vs. O: 28 ± 3% CVCmax; P < 0.05). NOS-I decreased VD in both groups compared with Co (Y: 20 ± 4; O: 15 ± 2% CVCmax; P < 0.05 vs. Co within group). Asc and Asc + A-I increased VD beyond Co in O (Asc: 35 ± 4% CVCmax; Asc + A-I: 41 ± 3% CVCmax; P < 0.001) but not in Y (Asc: 36 ± 3% CVCmax; Asc + A-I: 40 ± 5% CVCmax; P > 0.05). Combined Asc + A-I resulted in a greater increase in VD than Asc alone in O ( P = 0.001). Acute Asc supplementation increased reflex VD in aged skin. Asc combined with arginase inhibition resulted in a further increase in VD above Asc alone, effectively restoring CVC to the level of young subjects.
Long-term mineralocorticoid receptor blockade reduces fibrosis and improves cardiac performance and coronary hemodynamics in elderly SHR
Authors: Susic Dinko , Varagic Jasmina , Ahn Jwari , Matavelli Luis , Frohlich Edward D.
Published: August 2006

Aldosterone has been implicated as one of the mediators of cardiovascular injury in various diseases. This study examines whether mineralocorticoid antagonism ameliorates or prevents the adverse cardiac effects of hypertension and aging. Male 22-wk-old spontaneously hypertensive rats (SHR) were divided into two groups, 15 rats in each. One group received no treatment; the other was given eplerenone (∼100 mg·kg−1·day−1). At the age of 54 wk, indexes of cardiovascular mass, systemic and regional hemodynamics, including coronary, left ventricular function, and myocardial collagen content, were determined in all rats. Hemodynamic studies were done in conscious rats. Arterial pressure was lowered only slightly in eplerenone-treated rats, and cardiac output and total peripheral resistance did not differ from control rats. Left and right ventricular and aortic mass indexes were unaffected by eplerenone; however, concentration of hydroxyproline in the right and left ventricle was decreased significantly ( P < 0.05) by eplerenone. This was accompanied by an improvement in left ventricular diastolic function and coronary hemodynamics. In conclusion, long-term therapy with the mineralocorticoid receptor antagonist eplerenone ameliorated adverse cardiac effects of both hypertension and aging in SHR. Thus reduction in myocardial fibrosis, paralleled by improvements in left ventricular function and coronary hemodynamics, was observed in eplerenone-treated SHR.
Left ventricular pressure-volume relationship in conscious mice
Authors: Joho Shuji , Ishizaka Shinji , Sievers Richard , Foster Elyse , Simpson Paul C. , Grossman William
Published: August 2006

With the availability of transgenic models, the mouse has become an increasingly important subject for genetic-hemodynamic studies. Recently, we developed a technique to measure left ventricular (LV) pressure in conscious mice with an implanted LV polyethylene tube. We extended our new method by evaluating the LV pressure-volume relationship and examined the feasibility of this method in this study. We studied 17 male mice (age, 11–20 wk) with a conductance catheter inserted into the LV through the polyethylene tube. Load-independent parameters of contractility derived from pressure-volume relationship [slope of the end-systolic pressure-volume relationship ( Ees), slope of the maximum first derivative of LV pressure (dP/d tmax)-end-diastolic volume (EDV) relation, and preload-recruitable stroke work (PRSW)] were evaluated by inferior vena caval occlusion with an implanted snare. LV function assessed by this technique on two different days showed that the parameters were very similar, indicating reproducibility. Both linear and nonlinear regression analyses were performed for Ees. Contractility was enhanced by isoproterenol ( Ees, 13.1 ± 6.6 to 20.8 ± 8.7 mmHg/μl; dP/d tmax-EDV, 496 ± 139 to 825 ± 178 mmHg·s−1·μl−1; and PRSW, 110 ± 23 to 127 ± 21 mmHg), depressed by atenolol ( Ees, 14.5 ± 6.1 to 4.6 ± 2.0 mmHg/μl; dP/d tmax-EDV, 543 ± 188 to 185 ± 94 mmHg·s−1·μl−1; and PRSW, 117 ± 20 to 70 ± 15 mmHg) and isoflurane ( Ees, 12.3 ± 6.0 to 5.7 ± 2.1 mmHg/μl; dP/d tmax-EDV, 528 ± 172 to 164 ± 68 mmHg/s·μl; and PRSW, 124 ± 19 to 48 ± 10 mmHg), significantly. In conclusion, this is the first description of the LV pressure-volume relationship in conscious mice. These findings suggest that this method is feasible to detect changes of contractility in the conscious state, allowing serial assessment of pressure-volume-derived cardiac function indexes over time without anesthesia or repeated surgery.
Resistin impairs endothelium-dependent dilation to bradykinin, but not acetylcholine, in the coronary circulation
Authors: Dick Gregory M. , Katz Paige S. , Farias Martin , Morris Michael , James Jeremy , Knudson Jarrod D. , Tune Johnathan D.
Published: August 2006

Elevated plasma levels of fat-derived signaling molecules are associated with obesity, vascular endothelial dysfunction, and coronary heart disease; however, little is known about their direct coronary vascular effects. Accordingly, we examined mechanisms by which one adipokine, resistin, affects coronary vascular tone and endothelial function. Studies were conducted in anesthetized dogs and isolated coronary artery rings. Resistin did not change coronary blood flow, mean arterial pressure, or heart rate. Resistin had no effect on acetylcholine-induced relaxation of artery rings; however, resistin did impair bradykinin-induced relaxation. Selective impairment was also observed in vivo, as resistin attenuated vasodilation to bradykinin but not to acetylcholine. Resistin had no effect on dihydroethidium fluorescence, an indicator of superoxide (O2−) production, and the inhibitory effect of resistin on bradykinin-induced relaxation persisted in the presence of Tempol, a superoxide dismutase mimetic. To determine whether resistin impaired production of and/or responses to nitric oxide (NO) or prostaglandins (e.g., prostacyclin; PGI2), we performed experiments with Nω-nitro-l-arginine methyl ester (l-NAME) and indomethacin. The effect of resistin to attenuate bradykinin-induced vasodilation persisted in the presence of l-NAME or indomethacin, suggesting resistin may act at a cell signaling point upstream of NO or PGI2 production. Resistin-induced endothelial dysfunction is not generalized, and it is not consistent with effects mediated by O2− or interference with NO or PGI2 signaling. The site of the resistin-induced impairment is unknown but may be at the bradykinin receptor or a closely associated signal transduction machinery proximal to NO synthase or cyclooxygenase.
A 1-D model to explore the effects of tissue loading and tissue concentration gradients in the revised Starling principle
Authors: Zhang Xiaobing , Adamson Roger H. , Curry Fitz-Roy E. , Weinbaum Sheldon
Published: August 2006

The recent experiments in Hu et al. ( Am J Physiol Heart Circ Physiol 279: H1724–H1736, 2000) and Adamson et al. ( J Physiol 557: 889–907, 2004) in frog and rat mesentery microvessels have provided strong evidence supporting the Michel-Weinbaum hypothesis for a revised asymmetric Starling principle in which the Starling force balance is applied locally across the endothelial glycocalyx layer rather than between lumen and tissue. These experiments were interpreted by a three-dimensional (3-D) mathematical model (Hu et al.; Microvasc Res 58: 281–304, 1999) to describe the coupled water and albumin fluxes in the glycocalyx layer, the cleft with its tight junction strand, and the surrounding tissue. This numerical 3-D model converges if the tissue is at uniform concentration or has significant tissue gradients due to tissue loading. However, for most physiological conditions, tissue gradients are two to three orders of magnitude smaller than the albumin gradients in the cleft, and the numerical model does not converge. A simpler multilayer one-dimensional (1-D) analytical model has been developed to describe these conditions. This model is used to extend Michel and Phillips’s original 1-D analysis of the matrix layer ( J Physiol 388: 421–435, 1987) to include a cleft with a tight junction strand, to explain the observation of Levick ( Exp Physiol 76: 825–857, 1991) that most tissues have an equilibrium tissue concentration that is close to 0.4 lumen concentration, and to explore the role of vesicular transport in achieving this equilibrium. The model predicts the surprising finding that one can have steady-state reabsorption at low pressures, in contrast to the experiments in Michel and Phillips, if a backward-standing gradient is established in the cleft that prevents the concentration from rising behind the glycocalyx.
Severity of myocardial injury following ischemia-reperfusion is increased in a mouse model of allergic asthma
Authors: Hazarika Surovi , Van Scott Michael R. , Lust Robert M.
Published: August 2006

Cardiovascular disease is common in asthmatic patients but often is attributed to respiratory drug therapy. With mounting evidence for an inflammatory role in the development of cardiovascular disease, we hypothesized that the inflammation associated with asthma adversely affects the cardiovascular system independent of therapeutic interventions. The hypothesis was tested in a murine model of myocardial ischemia-reperfusion injury. BALB/C mice were sensitized by intraperitoneal injection of ragweed (RW) or normal saline (NS) and challenged by intratracheal instillation of RW or NS. Effective allergic sensitization and challenge were confirmed by hyperresponsiveness to aerosolized methacholine and bronchoalveolar lavage. In vivo myocardial ischemia-reperfusion injury was induced by ligation of the left anterior descending artery for 20 min, followed by reperfusion for 2 h. The infarct size (% risk area) and neutrophil density in the myocardial area at risk were significantly higher in the RW/RW group than in the control groups. The tissue neutrophil count correlated with the infarct size but did not correlate with blood neutrophil counts. Furthermore, in the RW/RW group, circulating granulocytes showed an enhanced expression of CD11b and P-selectin glycoprotein ligand-1, enhanced stimulated release of myeloperoxidase, and enhanced expression of P-selectin in the coronary vasculature. These results indicate that allergic responses in the airways enhance expression of attachment molecules in coronary vasculature and activate circulating neutrophils, resulting in recruitment of highly activated neutrophils to the infarct zone during an acute ischemia-reperfusion event, thereby enhancing tissue destruction.
Proteasome dysfunction inhibits surfactant protein gene expression in lung epithelial cells: mechanism of inhibition of SP-B gene expression
Authors: Das Aparajita , Boggaram Vijayakumar
Published: August 2006

Surfactant proteins maintain lung function through their actions to reduce alveolar surface tension and control of innate immune responses in the lung. The ubiquitin proteasome pathway is responsible for the degradation of majority of intracellular proteins in eukaryotic cells, and proteasome dysfunction has been linked to the development of neurodegenerative, cardiac, and other diseases. Proteasome function is impaired in interstitial lung diseases associated with surfactant protein C (SP-C) mutation mapping to the BRICHOS domain located in the proSP-C protein. In this study we determined the effects of proteasome inhibition on surfactant protein expression in H441 and MLE-12 lung epithelial cells to understand the relationship between proteasome dysfunction and surfactant protein gene expression. Proteasome inhibitors lactacystin and MG132 reduced the levels of SP-A, SP-B, and SP-C mRNAs in a concentration-dependent manner in H441 and MLE-12 cells. In H441 cells, lactacystin and MG132 inhibition of SP-B mRNA was associated with similar decreases in SP-B protein, and the inhibition was due to inhibition of gene transcription. Proteasome inhibitors decreased thyroid transcription factor-1 (TTF-1)/Nkx2.1 DNA binding activity, and the reduced TTF-1 DNA binding activity was due to reduced expression levels of TTF-1 protein. These data indicated that the ubiquitin proteasome pathway is essential for the maintenance of surfactant protein gene expression and that disruption of this pathway inhibits surfactant protein gene expression via reduced expression of TTF-1 protein.
Sulforaphane-stimulated phase II enzyme induction inhibits cytokine production by airway epithelial cells stimulated with diesel extract
Authors: Ritz Stacey A. , Wan Junxiang , Diaz-Sanchez David
Published: August 2006

Airborne particulate pollutants, such as diesel exhaust particles, are thought to exacerbate lung and cardiovascular diseases through induction of oxidative stress. Sulforaphane, derived from cruciferous vegetables, is the most potent known inducer of phase II enzymes involved in the detoxification of xenobiotics. We postulated that sulforaphane may be able to ameliorate the adverse effects of pollutants by upregulating expression of endogenous antioxidant enzymes. Stimulation of bronchial epithelial cells with the chemical constituents of diesel particles result in the production of proinflammatory cytokines. We first demonstrated a role for phase II enzymes in regulating diesel effects by transfecting the airway epithelial cell line (BEAS-2B) with the sentinel phase II enzyme NAD(P)H: quinine oxidoreductase 1 (NQO1). IL-8 production in response to diesel extract was significantly reduced in these compared with untransfected cells. We then examined whether sulforaphane would stimulate phase II induction and whether this would thereby ablate the effect of diesel extracts on cytokine production. We verified that sulforaphane significantly augmented expression of the phase II enzyme genes GSTM1 and NQO1 and confirmed that sulforaphane treatment increased glutathione S-transferase activity in epithelial cells without inducing cell death or apoptosis. Sulforaphane pretreatment inhibited IL-8 production by BEAS-2B cells upon stimulation with diesel extract. Similarly, whereas diesel extract stimulated production of IL-8, granulocyte-macrophage colony-stimulating factor, and IL-1β from primary human bronchial epithelial cells, sulforaphane pretreatment inhibited diesel-induced production of all of these cytokines. Our studies show that sulforaphane can mitigate the effect of diesel in respiratory epithelial cells and demonstrate the chemopreventative potential of phase II enzyme enhancement.
Subcellular distribution of the TSC2 gene product tuberin in human airway smooth muscle cells is driven by multiple localization sequences and is cell-cycle dependent
Authors: Clements Debbie , Mayer R. John , Johnson Simon R.
Published: August 2006

The products of the tuberous sclerosis complex (TSC) genes, hamartin and tuberin (TSC1 and 2), form a heteromer, which represses the kinase mammalian target of rapamycin. Loss of TSC1 or 2 results in diseases characterized by loss of cell-cycle control, including TSC and lymphangioleiomyomatosis. As tuberin has multiple signaling inputs, including phosphatidylinositide-3-OH kinase, mitogen-activated protein kinase, and adenosine monophosphate kinase, we postulated tuberin would have multiple protein interactions governed by subcellular localization and cellular status and examined this in primary human airway smooth muscle cells. Using immunofluorescence and confocal microscopy, tuberin was detected in cytoplasm, nucleus, nucleoli, and mitochondria. Fractionation of synchronized airway smooth cells showed that tuberin enters the nucleus in late G1, and passage through the cell cycle is necessary for nuclear entry. Deletion constructs showed localization sequences for the nucleus between amino acids 1351 and 1807, for mitochondria between 901 and 1350, and for cytoplasmic speckles between 1 and 450. Using fluorophore-tagged proteins, we observed fluorescence resonance energy transfer between tuberin and hamartin within these speckles, indicating a direct interaction between the proteins at this site. The observations that tuberin is localized to mitochondria and translocated to the nucleus in G1 are novel and consistent with interactions with proteins within multiple signaling pathways. Dynamic relocalization of tuberin may control these interactions to integrate these pathways. As tuberin has potential roles in proliferation, migration, and cell phenotype, it therefore warrants further investigation in diseases categorized by abnormalities in airway smooth muscle.
Use of a hanging-weight system for isolated renal artery occlusion during ischemic preconditioning in mice
Authors: Grenz Almut , Eckle Tobias , Zhang Hua , Huang Dan Yang , Wehrmann Manfred , Köhle Christoph , Unertl Klaus , Osswald Hartmut , Eltzschig Holger K.
Published: August 2006

Renal failure from ischemia contributes to morbidity and mortality. Ischemic preconditioning (IP) represents a powerful strategy for kidney protection, and recent advances in transgenic mice may help elucidate its molecular mechanisms. However, murine IP is technically challenging and experimental details significantly influence results. Thus we developed a novel model for renal IP using a hanging-weight system for isolated renal artery occlusion. In contrast to previous models, this technique eliminates the need for clamping the vascular pedicle (artery/vein). In fact, assessment of renal injury after different time periods of ischemia (10–60 min) revealed highly reproducible increases in plasma creatinine and potassium levels, while creatinine clearance, urinary flow and potassium/sodium excretion were significantly attenuated. Using different numbers of IP cycles, we found maximal protection with four cycles of 4 min of ischemia-reperfusion. In contrast, no significant renal protection was observed with IP of the vascular pedicle. To assess transcriptional responses in this model, we isolated RNA from preconditioned kidneys and found time-dependent induction of erythropoietin mRNA and plasma levels with IP. Taken together, this model provides highly reproducible renal injury and protection by IP, thus minimizing variability associated with previous techniques based on clamping of the renal pedicle. Further studies on renal ischemia/IP in mice may consider this technique.
LKB1/STK11 Suppresses Cyclooxygenase-2 Induction and Cellular Invasion through PEA3 in Lung Cancer
Authors: Upadhyay Sunil , Liu Chunyan , Chatterjee Aditi , Hoque Mohammad O. , Kim Myoung Sook , Engles James , Westra William , Trink Barry , Ratovitski Edward , Sidransky David
Published: August 2006

We showed that the PEA3 transcriptional factor interacted with LKB1, a serine/threonine kinase, which is somatically mutated in lung cancer. This interaction occurred through the ETS domain of PEA3 and the kinase domain of LKB1. Mutation of LKB1 in lung cancer cells stabilized PEA3. Reintroduction of wild-type (WT) LKB1 into cells induced down-regulation of PEA3 and subsequently resulted in reduced cyclooxygenase-2 RNA and protein expression, whereas germ-line and somatic LKB1 mutants were defective in this activity. LKB1 phosphorylated PEA3 and promoted its degradation through a proteasome-mediated mechanism. Cells expressing mutant LKB1 possessed greater invasive potential compared with cells expressing WT LKB1. Increased invasion of cells with mutant LKB1 was partly due to PEA3 expression, as RNA interference inhibition of PEA3 resulted in dramatic decrease of Matrigel invasion. However, forced expression of PEA3 resulted in down-regulation of epithelial markers and induction of mesenchymal markers. These results suggest that PEA3 stabilization due to LKB1 inactivation could lead to epithelial/mesenchymal transition and greater lung cancer invasion potential. (Cancer Res 2006; 66(16): 7870-9)
Met, the Hepatocyte Growth Factor Receptor, Localizes to the Nucleus in Cells at Low Density
Authors: Pozner-Moulis Sharon , Pappas Derek J. , Rimm David L.
Published: August 2006

Some breast cancer cases in our previous immunohistochemical studies show Met expression in the nucleus. Given nuclear localization of other receptor tyrosine kinases, we proceeded to investigate Met. Nuclear Met is seen in numerous cell lines and in germinal regions of many tissues using four unique antibodies. Cell fractionation reveals a 60-kDa band recognized by COOH-terminal Met antibodies that is present independent of hepatocyte growth factor treatment. Green fluorescent protein (GFP) fusion proteins of the cytoplasmic domain of Met transfected into HEK293 cells are found in the nucleus whereas the full-length Met-GFP fusion is membranous. Further deletions of the Met-GFP fusions identify a region of the juxtamembrane domain required for nuclear translocation. In a CaCo2 cell line model for epithelial maturation, we find that Met is initially nuclear, and then becomes membranous, after confluence. This work suggests processing of the Met receptor, analogous to ErbB4, resulting in the release of the cytoplasmic domain and its translocation to the nucleus in cells at low density. (Cancer Res 2006; 66(16): 7976-82)
Cellular Retinoic Acid–Binding Protein II Is a Direct Transcriptional Target of MycN in Neuroblastoma
Authors: Gupta Anu , Williams Bryan R.G. , Hanash Samir M. , Rawwas Jawhar
Published: August 2006

Neuroblastoma is a heterogeneous disease in which 22% of tumors show MycN oncogene amplification and are associated with poor clinical outcome. MycN is a transcription factor that regulates the expression of a number of proteins that affect the clinical behavior of neuroblastoma. We report here that cellular retinoic acid–binding protein II (CRABP-II) is a novel MycN target, expressed at significantly higher levels in primary neuroblastoma tumors with mycN oncogene amplification as compared with non–MycN-amplified tumors. Moreover, regulated induction and repression of MycN in a neuroblastoma-derived cell line resulted in temporal and proportionate expression of CRABP-II. CRABP-II is expressed in several cancers, but its role in tumorigenesis has not been elucidated. We show that MycN binds to the promoter of CRABP-II and induces CRABP-II transcription directly. In addition, CRABP-II-transfected neuroblastoma cell lines show an increase in MycN protein levels resulting in increased cell motility. Gene expression profiling of CRABP-II-expressing cell lines uncovered increased expression of the HuB (Hel N1) gene. Hu proteins have been implicated in regulating the stability of MycN mRNA and other mRNAs by binding to their 3′ untranslated regions. We did not, however, observe any change in MycN mRNA stability or protein half-life in response to CRABP-II expression. In contrast, de novo MycN protein synthesis was increased in CRABP-II-expressing neuroblastoma cells, thereby suggesting an autoregulatory loop that might exacerbate the effects of MycN gene amplification and affect the clinical outcome. Our findings also suggest that CRABP-II may be a potential therapeutic target for neuroblastoma. (Cancer Res 2006; 66(16): 8100-8)