bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogenetic position of the small Kashmir flying squirrel, Hylopetes fimbriatus (≡ Eoglaucomys fimbriatus), in the subfamily Pteromyinae
Authors: Oshida Tatsuo , Shafique Chaudhry M , Barkati Sohail , Yasuda Masatoshi , Hussein Nor Azman , Endo Hideki , Yanagawa Hisashi , Masuda Ryuichi
Published: January 2005

The phylogenetic relationships of flying squirrels (Pteromyinae) were studied by obtaining complete sequence data from the mitochondrial cytochrome b gene of eight Old World and two New World flying squirrel species, with special reference to the systematic and phylogenetic status among Hylopetes fimbriatus (Gray, 1837) (≡ Eoglaucomys fimbriatus (Gray, 1837)) from Pakistan, two Glaucomys Thomas, 1908 species from North America, and two Hylopetes Thomas, 1908 species from Southeast Asia. Phylogenetic trees supported clustering of (i) Belomys pearsonii (Gray, 1842), (ii) H. fimbriatus, the Glaucomys species, Hylopetes lepidus (Horsfield, 1823), and Hylopetes phayrei (Blyth, 1859), (iii) species of Pteromys G. Cuvier, 1800, and (iv) species of Petaurista Link, 1795. Early polytomic divergence among the flying squirrel genera could have taken place in the northern part of the Eurasian continent. The unclear divergence between the Old and New World flying squirrels shows that divergence among flying squirrel genera could have occurred before the formation of the Bering Strait. Hylopetes fimbriatus was more closely related to the two Glaucomys species than to H. lepidus or H. phayrei, supporting placement of the species fimbriatus in the monotypic genus Eoglaucomys Howell, 1915.
Microhabitat separation during winter among sympatric giant pandas, red pandas, and tufted deer: the effects of diet, body size, and energy metabolism
Authors: Zhang Zejun , Wei Fuwen , Li Ming , Zhang Baowei , Liu Xuehua , Hu Jinchu
Published: January 2005

The giant panda (Ailuropoda melanoleuca (David, 1869)), red panda (Ailurus fulgens F.G. Cuvier, 1825), and tufted deer (Elaphodus cephalophus Milne-Edwards, 1872) are endemic to the Himalayan Hengduan Mountains; the red panda extends into India, Burma, Bhutan, and Nepal, and the tufted deer extends marginally into Burma, while the giant panda is endemic to China. In Sichuan Province, uniquely, all three species occur sympatrically. We investigated microhabitat characteristics at 150 fecal-group sites from November 2002 to March 2003 to improve understanding of microhabitat separation among the three species at the Fengtongzhai Nature Reserve, Baoxing County, Sichuan Province, People's Republic of China. Density and height of bamboo were greater in the giant and red pandas' micro habitats than in those of the tufted deer. The red panda preferred microhabitats with greater tree-stump density, smaller trees, and shorter fallen log dispersion distance than the other two species. Tufted deer often occurred at sites with greater shrub density and herb cover and more open land with poorer concealment conditions than sites where the two panda species occurred. Both pandas' microhabitats were mostly concentrated on the upper hillside, unlike those of the tufted deer. The giant panda preferred microhabitats with a gentler slope and lower density of fallen logs. Selection of specific microhabitats by each species is an ecological adaptation dependent on behavior linked to its diet, body size, energy metabolism, and other factors. Microhabitat separation among these species reflects the integrated effects of their differences in diet, body size, and energy metabolism, which could facilitate their successful coexistence.
Fish assemblage structure and relations with environmental conditions in a Rocky Mountain watershed
Authors: Quist Michael C , Hubert Wayne A , Isaak Daniel J
Published: January 2005

Fish and habitat were sampled from 110 reaches in the Salt River basin (Idaho and Wyoming) during 1996 and 1997 to assess patterns in fish assemblage structure across a Rocky Mountain watershed. We identified four distinct fish assemblages using cluster analysis: (1) allopatric cutthroat trout (Oncorhynchus clarki (Richardson, 1836)); (2) cutthroat trout – brook trout (Salvelinus fontinalis (Mitchell, 1814)) – Paiute sculpin (Cottus beldingi Eigenmann and Eigenmann, 1891); (3) cutthroat trout – brown trout (Salmo trutta L., 1758) – mottled sculpin (Cottus bairdi Girard, 1850); and (4) Cyprinidae–Catostomidae. The distribution of fish assemblages was explained by thermal characteristics, stream geomorphology, and local habitat features. Reaches with allopatric cutthroat trout and the cutthroat trout – brook trout – Paiute sculpin assemblage were located in high-elevation, high-gradient streams. The other two fish assemblages were generally located in low-elevation streams. Associations between habitat gradients, locations of reaches in the watershed, and occurrence of species were further examined using canonical correspondence analysis. The results suggest that stream geomorphology, thermal conditions, and local habitat characteristics influence fish assemblage structure across a Rocky Mountain watershed, and they provide information on the ecology of individual species that can guide conservation activities.
At-sea behavior of juvenile male northern fur seals (Callorhinus ursinus)
Authors: Sterling J T , Ream R R
Published: January 2005

The at-sea behavior of juvenile male northern fur seals, Callorhinus ursinus (L., 1758), captured at two haul-out sites on St. Paul Island, Alaska, during the 1999 and 2000 breeding seasons (July–September) was studied. To compare at-sea locations, dive behavior, and changes in body mass, 31 juveniles between the estimated ages of 3–6 years were captured, instrumented, and released. Individuals behaved like central-place foragers by making trips to sea and returning to the Pribilof Islands. Trip durations ranged between 8.74 and 29.81 d, whereas distances from departure site ranged between 171.27 and 680.68 km (maximum straight-line distance). Differences in maximum straight-line distance traveled and trip duration were not observed when comparing years or departure site. Diving tended to reflect patterns associated with different bathymetric domains; shallow nighttime diving was common in ~3000 m deep waters, whereas deeper diving was generally observed in <200 m deep waters. Proportion of body mass gained over a single trip to sea averaged 27.8% (range 3%–65%, n = 19). Mass gain was similar between individuals that dove in shallow waters (over the continental shelf; 10.9 ± 1.8 kg (mean ± 1 SE), n = 11) versus individuals that dove in pelagic waters (8.5 ± 1.0 kg, n = 8). These results demonstrate that the at-sea behavior of juvenile males can extend farther from the Pribilof Islands when compared with previous reports of parturient female at-sea behavior, thus revealing important variation within this species.
Wavelength-dependent waveform characteristics of tectal evoked potentials in rainbow trout
Authors: McDonald C G , Haimberger T J , Hawryshyn C W
Published: January 2005

Wavelength-dependent properties of tectal evoked potentials (TEPs) in rainbow trout, Oncorhynchus mykiss (Walbaum, 1792), were examined. It was found that TEP waveforms show distinct variation as a function of wavelength. In addition, the data suggest that the On and Off channels of the tectum each possess different wavelength-dependent characteristics. Middle wavelength stimulation typically evoked a waveform similar to that reported for another anamniote vertebrate, the toad (genus Bufo Laurenti, 1768). For the On and Off responses, this waveform comprised two negative deflections, N1 and N2, which were interrupted by a positive deflection, P2. The N2 deflection was followed by a final positive deflection, P3. Principal component analysis revealed that the N2–P3 complex of the On response was significantly more pronounced at longer wavelengths. In contrast, the N2–P3 complex was most pronounced at middle wavelengths for the Off response. The N1 deflection was relatively invariant with respect to wavelength. Should colour-opponent tectal units provide a significant contribution to the TEP, it is probable that its waveform characteristics provide signs of underlying neural processes which facilitate colour discrimination.
Seasonal variability in the gut ultrastructure of the parasitic copepod Neoergasilus japonicus (Copepoda, Poecilostomatoida)
Authors: Baud A , Cuoc C , Grey J , Chappaz R , Alekseev V
Published: January 2005

The gut structure and ultrastructure of Neoergasilus japonicus (Harada, 1930), a copepod from the family Ergasilidae (Copepoda, Poecilostomatoida) and a parasite of fish, were compared at different periods of the life cycle: in free-living specimens in October and after attaching to fish in January and June. Differences in the depth of the intestinal epithelium were prominent and other cellular characteristics appeared seasonally variable. We relate these to changes in the physiological activity. Preliminary data from stable-isotope analyses of attached specimens suggest nutritional contribution from parasitism. The possibility of a diapause in the life cycle, as well as the relationship between the morphology of the gut and early evolutionary parasitism of N. japonicus, are discussed.
CALCULATION OF BINDING ENERGY FOR THE CHARGE-NONSYMMETRIC MUONIC MOLECULES IN THE HYPER-SPHERICAL APPROACH
Authors: ESKANDARI M. R. , MAHDAVI M.
Published: January 2005

The hyper-spherical adiabatic expansion is a representation for the investigation of the muonic three-body bound states. In this research we have used the method of hyper-spherical "surface" functions for charge-nonsymmetric muonic molecules (isotopes of helium-deuterium-muon). Through this approach, the binding energy of the ground state and the lowest eigenpotentials for the muonic molecular ions are calculated in extreme adiabatic approximation. The obtained results are close to other's calculation.
TRANSIENT CONDUCTIVE–RADIATIVE HEAT TRANSFER: DISCRETE EXISTENCE AND UNIQUENESS FOR A FINITE VOLUME SCHEME
Authors: KLEIN OLAF , PHILIP PETER
Published: January 2005

This article presents a finite volume scheme for transient nonlinear heat transport equations coupled by nonlocal interface conditions modeling diffuse-gray radiation between the surfaces of (both open and closed) cavities. The model is considered in three space dimensions; modifications for the axisymmetric case are indicated. Proving a maximum principle as well as existence and uniqueness for roots to a class of discrete nonlinear operators that can be decomposed into a scalar-dependent sufficiently increasing part and a benign rest, we establish a discrete maximum principle for the finite volume scheme, yielding discrete L∞-L∞ a priori bounds as well as a unique discrete solution to the finite volume scheme. We present results of numerical experiments to illustrate the effectiveness of the considered scheme.
Chloride conductance of CFTR facilitates basal Cl−/HCO3−exchange in the villous epithelium of intact murine duodenum
Authors: Simpson Janet E. , Gawenis Lara R. , Walker Nancy M. , Boyle Kathryn T. , Clarke Lane L.
Published: January 2005

Villi of the proximal duodenum are situated for direct exposure to gastric acid chyme. However, little is known about active bicarbonate secretion across villi that maintains the protective alkaline mucus barrier, a process that may be compromised in cystic fibrosis (CF), i.e., in the absence of a functional CF transmembrane conductance regulator (CFTR) anion channel. We investigated Cl−/HCO3−exchange activity across the apical membrane of epithelial cells located at the midregion of villi in intact duodenal mucosa from wild-type (WT) and CF mice using the pH-sensitive dye BCECF. Under basal conditions, the Cl−/HCO3−exchange rate was reduced by ∼35% in CF compared with WT villous epithelium. Cl−/HCO3−exchange in WT and CF villi responded similarly to inhibitors of anion exchange, and membrane depolarization enhanced rates of Cl−out/HCO3−inexchange in both epithelia. In anion substitution studies, anionin/HCO3−outexchange rates were greater in WT epithelium using Cl−or NO3−, but decreased to the level of the CF epithelium using the CFTR-impermeant anion, SO42−. Similarly, treatment of WT epithelium with the CFTR-selective blocker glybenclamide decreased the Cl−/HCO3−exchange rate to the level of CF epithelium. The mRNA expression of Slc26a3 (downregulated in adenoma) and Slc26a6 (putative anion exchanger-1) was similar between WT and CF duodena. From these studies of murine duodenum, we conclude 1) characteristics of Cl−/HCO3−exchange in the villous epithelium are most consistent with Slc26a6 activity, and 2) Cl−channel activity of CFTR facilitates apical membrane Cl−in/HCO3−outexchange by providing a Cl−“leak” under basal conditions.
Exercise training improves endogenous nitric oxide mechanisms within the paraventricular nucleus in rats with heart failure
Authors: Zheng Hong , Li Yi-Fan , Cornish Kurt G. , Zucker Irving H. , Patel Kaushik P.
Published: January 2005

Previously, we have demonstrated that an altered endogenous nitric oxide (NO) mechanism within the paraventricular nucleus (PVN) contributes to increased renal sympathetic nerve activity (RSNA) in heart failure (HF) rats. The goal of this study was to examine the effect of exercise training (ExT) in improving the endogenous NO mechanism within the PVN involved in the regulation of RSNA in rats with HF. ExT significantly restored the decreased number of neuronal NO synthase (nNOS)-positive neurons in the PVN (129 ± 17 vs. 99 ± 6). nNOS mRNA expression and protein levels in the PVN were also significantly increased in HF-ExT rats compared with HF-sedentary rats. To examine the functional role of NO within the PVN, an inhibitor of NOS, NG-monomethyl-l-arginine, was microinjected into the PVN. Dose-dependent increases in RSNA, arterial blood pressure (BP), and heart rate (HR) were produced in all rats. There was a blunted increase in these parameters in HF rats compared with the sham-operated rats. ExT significantly augmented RSNA responses in rats with HF (33% vs. 20% at the highest dose), thus normalizing the responses. The NO donor sodium nitroprusside, microinjected into the PVN, produced dose-dependent decreases in RSNA, BP, and HR in both sham and HF rats. ExT significantly improved the blunted decrease in RSNA in HF rats (36% vs. 17% at the highest dose). In conclusion, our data indicate that ExT improves the altered NO mechanism within the PVN and restores NO-mediated changes in RSNA in rats with HF.
Extending the cardioprotective window using a novel δ-opioid agonist fentanyl isothiocyanate via the PI3-kinase pathway
Authors: Gross Eric R. , Peart Jason N. , Hsu Anna K. , Auchampach John A. , Gross Garrett J.
Published: January 2005

Selective δ-opioid agonists produce delayed cardioprotection that lasts for 24–48 h in rats; however, the maximum length of the cardioprotective window is unclear. In this study, we attempted to prolong the cardioprotective window using a unique δ-opioid agonist, fentanyl isothiocyanate (FIT), which binds irreversibly to the δ-receptor, and determined the role of the phosphatidylinositol 3-kinase (PI3K) pathway as a trigger or end effector of FIT-induced cardioprotection. Initially, male rats were administered FIT (10 μg/kg) 10 min before hearts were subjected to 30 min of ischemia and 2 h of reperfusion followed by infarct size (IS) assessment. Acute FIT administration reduced IS when given before ischemia, 5 min before reperfusion, or 10 s after reperfusion compared with control. IS reduction also occurred following a single dose of FIT at 48, 72, 96, and 120 h after administration vs. control, with the maximum effect observed at 96 h. FIT-induced IS reduction at 96 h was completely abolished when the irreversible PI3K inhibitor wortmannin (15 μg/kg) was given before FIT during the trigger phase; however, the effect was only partially abrogated when wortmannin was given 96 h later. These data suggest that FIT has a prolonged cardioprotective window greater than that of any previously described cardioprotective agent that requires PI3K primarily in the trigger phase but also partially, as a mediator or end effector.
Adipokines: molecular links between obesity and atheroslcerosis
Authors: Lau David C. W. , Dhillon Bikramjit , Yan Hongyun , Szmitko Paul E. , Verma Subodh
Published: January 2005

Atherosclerotic disease remains the leading cause of death in industrialized nations despite major advances in its diagnosis, treatment, and prevention. The increasing epidemic of obesity, insulin resistance, and diabetes will likely add to this burden. Increasingly, it is becoming apparent that adipose tissue is an active endocrine and paracrine organ that releases several bioactive mediators that influence not only body weight homeostasis but also inflammation, coagulation, fibrinolysis, insulin resistance, diabetes, and atherosclerosis. The cellular mechanisms linking obesity and atherosclerosis are complex and have not been fully elucidated. This review summarizes the experimental and clinical evidence on how excess body fat influences cardiovascular health through multiple yet converging pathways. The role of adipose tissue in the development of obesity-linked insulin resistance, metabolic syndrome, and diabetes will be reviewed, including an examination of the molecular links between obesity and atherosclerosis, namely, the effects of fat-derived adipokines. Finally, we will discuss how these new insights may provide us with innovative therapeutic strategies to improve cardiovascular health.
Lesions of the anteroventral third ventricle region (AV3V) disrupt cardiovascular responses to an elevation in core temperature
Authors: Whyte Douglas G. , Johnson Alan Kim
Published: January 2005

Blood flow is redistributed from the viscera to the periphery during periods of heat stress to maximize heat loss. The heat-induced redistribution of blood flow is strongly influenced by nonthermal inputs such as hydration status. At present, little is known about where thermal and nonthermal information is integrated to generate an appropriate effector response. Recently, the periventricular tissue that surrounds the anteroventral third ventricle (AV3V) has been implicated in the integration of thermal and osmotic information. The purpose of the present study was to determine the effects of electrolytic lesions of the AV3V on the cardiovascular response to a passive heat stress in unanesthetized, free-moving male Sprague-Dawley rats. Core temperature was elevated at a constant rate of ∼0.03°C/min in sham- and AV3V-lesion rats using an infrared heat lamp. Changes in mesenteric and hindquarter vascular resistance were determined using Doppler flow probes, and heat-induced salivation was estimated using the spit-print technique. The rise in mean arterial pressure (MAP), heart rate (HR), and mesenteric resistance in response to elevations in core temperature were all attenuated in AV3V-lesion rats; however, hindquarter resistance was unaffected. Heat-induced salivation was also diminished. In addition, AV3V-lesion rats were more affected by the novelty of the experimental environment, resulting in a higher basal core temperature, HR, and MAP. These results indicate that AV3V lesions disrupt the cardiovascular and salivatory response to a passive heat stress in rats and produce an exaggerated stress-induced fever triggered by a novel environment.
Age-related differences in apoptosis with disuse atrophy in soleus muscle
Authors: Leeuwenburgh Christiaan , Gurley Cathy M. , Strotman Beau A. , Dupont-Versteegden Esther E.
Published: January 2005

Muscle atrophy is associated with a loss of muscle fiber nuclei, most likely through apoptosis. We investigated age-related differences in the extent of apoptosis in soleus muscle of young (6 mo) and old (32 mo) male Fischer 344 × Brown Norway rats subjected to acute disuse atrophy induced by 14 days of hindlimb suspension (HS). HS-induced atrophy (reduction in muscle weight and cross-sectional area) was associated with loss of myofiber nuclei in soleus muscle of young, but not old, rats. This resulted in a significant decrease in the myonuclear domain (cross-sectional area per nucleus) in young and old rats, with changes being more pronounced in old animals. Levels of apoptosis (TdT-mediated dUTP nick end labeling and DNA fragmentation) were higher in soleus muscles of old control rats than young animals. Levels were significantly increased with HS in young and old rats, with the greatest changes in old animals. Caspase-3 activity in soleus muscle tended to be increased with age, but changes were not statistically significant ( P = 0.052). However, with HS, caspase-3 activity significantly increased in young, but not old, rats. Immunohistochemistry showed that the proapoptotic endonuclease G (EndoG, a mitochondrion-specific nuclease) was localized in the subsarcolemmal mitochondria in control muscles, and translocation to the nucleus occurred in old, but not young, control animals. There was no difference between EndoG total protein content in young and old control rats, but EndoG increased almost fivefold in soleus muscle of old, but not young, rats after HS. These results show that deregulation of myonuclear number occurs in old skeletal muscle and that the pathways involved in apoptosis are distinct in young and old muscles. Apoptosis in skeletal muscle is partly mediated by the subsarcolemmal mitochondria through EndoG translocation to the nucleus in response to HS.
Roles of nitric oxide and prostaglandins in pathogenesis of delayed colonic transit after burn injury in rats
Authors: Gan Hua Tian , Chen J. D. Z.
Published: January 2005

Burn injury has been shown to impair gut transit, but the exact mechanism remains unknown. The present study investigated whether nitric oxide synthase (NOS) and cyclooxygenase (COX) mediated changes in burn-induced colonic transit. After rats underwent 30% total body surface area burn injury, they were injected with S-methylisothiourea (SMT, selective inducible NOS inhibitor), 7-nitronidazole (7-NI, selective neuronal NOS inhibitor), and nimesulide (NIM, selective COX-2 inhibitor), respectively. The protein and mRNA of NOS and COX-2 were measured by Western blot analysis and real-time RT-RCR, and localization of NOS and COX-2 protein was determined by immunohistochemistry. Our results showed that colonic transit assessed by the geometric center was delayed from 3.47 ± 0.28 in controls to 2.21 ± 0.18 after burn ( P < 0.009). SMT and NIM significantly improved colonic transit in burned rats but had no effect in sham-operated rats. 7-NI failed to modify delayed transit in burned rats but significantly delayed colonic transit in sham-operated rats. Both protein and mRNA of inducible NOS and COX-2 increased significantly but not neuronal NOS in burned rats. Inducible NOS protein expression was noted not only in epithelial cells but also in neurons of the myenteric ganglia in burned rats. These findings suggest that nitric oxide (NO) produced by neuronal NOS plays an important role in mediating colonic transit under the physiological condition. NO produced by inducible NOS and prostaglandins synthesized by COX-2 are both involved in the pathogenesis of delayed colonic transit after burn injury. Inducible NOS expression in neurons of the myenteric ganglia may contribute to dysmotility with burn injury.
Effects of eccentric exercise training on cortical bone and muscle strength in the estrogen-deficient mouse
Authors: Hubal M. J. , Ingalls C. P. , Allen M. R. , Wenke J. C. , Hogan H. A. , Bloomfield S. A.
Published: January 2005

The purpose of this study was to determine whether eccentrically biased exercise training could attenuate changes in muscle and bone function associated with estrogen deficiency in the mouse model. Four groups of ICR mice were used: control (Con), sham ovariectomized (Sham), ovariectomized (OVX), and ovariectomized + high-force resistance training (OVX+Train). All groups except Con were implanted with a nerve cuff surrounding the peroneal nerve to stimulate the left ankle dorsiflexors. Training consisted of 30 stimulated eccentric contractions of the left ankle dorsiflexors at ∼150% of peak isometric torque every third day for 8 wk. After the training period, groups were not significantly different with regard to peak torque or muscle size. However, the tibial midshaft of the trained leg in the OVX+Train mice exhibited greater stiffness (+15%) than that in the untrained OVX mice, which could not be explained by changes in cross-sectional geometry of the tibia. Scaling of bone mechanical properties to muscle strength were not altered by ovariectomy or training. These data indicate that eccentric exercise training in adult mice can significantly increase bone stiffness, despite the absence of ovarian hormones.
Orthostatic blood pressure control before and after spaceflight, determined by time-domain baroreflex method
Authors: Gisolf J. , Immink R. V. , van Lieshout J. J. , Stok W. J. , Karemaker J. M.
Published: January 2005

Reduction in plasma volume is a major contributor to orthostatic tachycardia and hypotension after spaceflight. We set out to determine time- and frequency-domain baroreflex (BRS) function during preflight baseline and venous occlusion and postflight orthostatic stress, testing the hypothesis that a reduction in central blood volume could mimic the postflight orthostatic response. In five cosmonauts, we measured finger arterial pressure noninvasively in supine and upright positions. Preflight measurements were repeated using venous occlusion thigh cuffs to impede venous return and “trap” an increased blood volume in the lower extremities; postflight sessions were between 1 and 3 days after return from 10- to 11-day spaceflight. BRS was determined by spectral analysis and by PRVXBRS, a time-domain BRS computation method. Although all completed the stand tests, two of five cosmonauts had drastically reduced pulse pressures and an increase in heart rate of ∼30 beats/min or more during standing after spaceflight. Averaged for all five subjects in standing position, high-frequency interbeat interval spectral power or transfer gain did not decrease postflight. Low-frequency gain decreased from 8.1 (SD 4.0) preflight baseline to 6.8 (SD 3.4) postflight ( P = 0.033); preflight with thigh cuffs inflated, low-frequency gain was 9.4 (SD 4.3) ms/mmHg. There was a shift in time-domain-determined pulse interval-to-pressure lag, Tau, toward higher values ( P < 0.001). None of the postflight results were mimicked during preflight venous occlusion. In conclusion, two of five cosmonauts showed abnormal orthostatic response 1 and 2 days after spaceflight. Overall, there were indications of increased sympathetic response to standing, even though we can expect (partial) restoration of plasma volume to have taken place. Preflight venous occlusion did not mimic the postflight orthostatic response.
Endogenous PGE2Regulates Membrane Excitability and Synaptic Transmission in Hippocampal CA1 Pyramidal Neurons
Authors: Chen Chu , Bazan Nicolas G.
Published: January 2005

The significance of cyclooxygenases (COXs), the rate-limiting enzymes that convert arachidonic acid (AA) to prostaglandins (PGs) in the brain, is unclear, although they have been implicated in inflammatory responses and in some neurological disorders such as epilepsy and Alzheimer's disease. Recent evidence that COX-2, which is expressed in postsynaptic dendritic spines, regulates PGE2signaling in activity-dependent long-term synaptic plasticity at hippocampal perforant path-dentate granule cell synapses, suggests an important role of the COX-2–generated PGE2in synaptic signaling. However, little is known of how endogenous PGE2regulates neuronal signaling. Here we showed that endogenous PGE2selectively regulates fundamental membrane and synaptic properties in the hippocampus. Somatic and dendritic membrane excitability was significantly reduced when endogenous PGE2was eliminated with a selective COX-2 inhibitor in hippocampal CA1 pyramidal neurons in slices. Exogenous application of PGE2produced significant increases in frequency of firing, excitatory postsynaptic potentials (EPSP) amplitude, and temporal summation in slices treated with the COX-2 inhibitor. The PGE2-induced increase in membrane excitability seemed to result from its inhibition of the potassium currents, which in turn, boosted dendritic Ca2+influx during dendritic-depolarizing current injections. In addition, the PGE2-induced enhancement of EPSPs was blocked by eliminating both PKA and PKC activities. These findings indicate that endogenous PGE2dynamically regulates membrane excitability, synaptic transmission, and plasticity and that the PGE2-induced synaptic modulation is mediated via cAMP-PKA and PKC pathways in rat hippocampal CA1 pyramidal neurons.
Membrane Microparticles: Two Sides of the Coin
Authors: Hugel Bénédicte , Martínez M. Carmen , Kunzelmann Corinne , Freyssinet Jean-Marie
Published: January 2005

Microparticles are plasma membrane-derived vesicles shed from stimulated cells, in the broad sense of the term. Their presence is interpreted by proximal or remote cells in fundamental physiological processes including intercellular communication, hemostasis, and immunity. On the other hand, variations of their number or characteristics are frequently observed in pathophysiological situations.
Airway Remodeling in Asthma: Therapeutic Implications of Mechanisms
Authors: Homer Robert J. , Elias Jack A.
Published: January 2005

Asthma is currently recognized as a chronic inflammatory disorder of the airways that leads to tissue injury and subsequent structural changes collectively called airway remodeling. Transgenic modeling of inflammatory mediators allows for the discovery of unexpected effects, dissection of downstream signaling events, and clues to future therapies.
Neurotrophin-Mediated Rapid Signaling in the Central Nervous System: Mechanisms and Functions
Authors: Blum Robert , Konnerth Arthur
Published: January 2005

Neurotrophins regulate growth, survival, and differentiation of central neurons. In addition to the “classical” effects that are relatively slow neurotrophins also elicit rapid signaling that modulates a variety of cellular functions such as membrane excitability, synaptic transmission, and activity-dependent synaptic plasticity. These rapid actions are mediated mainly through the interaction of Trk receptors with ion channels and ionotropic receptors in the plasma membrane.
Platelet Heterogeneity
Authors: Kempton Christine L. , Hoffman Maureane , Roberts Harold R. , Monroe Dougald M.
Published: January 2005

Objective—

Previous work has shown that platelets stimulated with the combination of thrombin and convulxin, a glycoprotein VI agonist, develop 2 populations with different levels of α-granule factor V bound to the platelet surface. To evaluate whether this phenomenon is restricted to α-granule components or is a feature that can be generalized to other coagulation factors, we studied the binding of factors V, VIII, IX, and X on the surface of platelets stimulated by convulxin and thrombin.

Methods and Results—

The relative amount of factors V, VIII, IX, and X on the surface of platelets stimulated with thrombin or convulxin plus thrombin was measured using flow cytometry. Simultaneous measurements of factor Xa and thrombin generation were obtained and correlated with the binding of coagulation factors on the platelet surface. The binding of factors V, VIII, IX, and X all increased on a subpopulation of platelets when stimulated with the combined agonists. The development of this platelet subpopulation is dependent on convulxin concentration and correlates with increases in factor Xa and thrombin generation.

Conclusions—

The development of increased coagulation factor binding to a subpopulation of platelets is not limited to α-granule components. Convulxin-induced increases in thrombin generation are regulated by the proportion of platelets with increased coagulation factor binding.
Dual Mechanisms Regulating AMPK Kinase Action in the Ischemic Heart
Authors: Baron Suzanne J. , Li Ji , Russell Raymond R. , Neumann Dietbert , Miller Edward J. , Tuerk Roland , Wallimann Theo , Hurley Rebecca L. , Witters Lee A. , Young Lawrence H.
Published: January 2005

AMP-activated protein kinase (AMPK) is emerging as an important signaling protein during myocardial ischemia. AMPK is a heterotrimeric complex containing an α catalytic subunit and β and γ regulatory subunits. Phosphorylation of Thr
172
in the activation loop of the α subunit by upstream AMPK kinase(s) (AMPKK) is a critical determinant of AMPK activity. However, the mechanisms regulating AMPK phosphorylation in the ischemic heart remain uncertain and were therefore investigated. In the isolated working rat heart, low-flow ischemia rapidly activated AMPKK activity when measured using recombinant AMPK (rAMPK) as substrate. The addition of AMP (10 to 200 μmol/L) augmented the ability of heterotrimeric α
1
β
1
γ
1
or α
2
β
1
γ
1
rAMPK to be phosphorylated by heart AMPKK in vitro, whereas physiologic concentrations of ATP inhibited rAMPK phosphorylation. However, neither AMP nor ATP directly influenced AMPKK activity: they had no effect on AMPKK-mediated phosphorylation of rAMPK substrates lacking normal AMP-binding γ subunits (isolated truncated α
1
1–312
or α
1
β
1
γ
1
rAMPK containing an R70Q mutation in the γ
1
AMP-binding site). Regional ischemia in vivo also increased AMPKK activity and AMPK phosphorylation in the rat heart. AMPK phosphorylation could also be induced in vivo without activating AMPKK: AICAR infusion increased AMPK phosphorylation without activating AMPKK; however, the AMP-mimetic AICAR metabolite ZMP enhanced the ability of heterotrimeric rAMPK to be phosphorylated by AMPKK. Thus, heart AMPKK activity is increased by ischemia and its ability to phosphorylate AMPK is highly modulated by the interaction of AMP and ATP with the heterotrimeric AMPK complex, indicating that dual mechanisms regulate AMPKK action in the ischemic heart.
Genetic Deletion of the A
1
Adenosine Receptor Limits Myocardial Ischemic Tolerance
Authors: Reichelt Melissa E. , Willems Laura , Molina Jose G. , Sun Chun-Xiao , Noble Janci C. , Ashton Kevin J. , Schnermann Jurgen , Blackburn Michael R. , Headrick John P.
Published: January 2005

Adenosine receptors may be important determinants of intrinsic ischemic tolerance. Genetically modified mice were used to examine effects of global A
1
adenosine receptor (A
1
AR) knockout (KO) on function and ischemic tolerance in perfused mouse hearts. Baseline contractile function and heart rate were unaltered by A
1
AR KO, which was shown to abolish the negative chronotropic effects of 2-chloroadenosine (A
1
AR-mediated) without altering A
2
adenosine receptor–mediated coronary dilation. Tolerance to 25 minutes global normothermic ischemia (followed by 45 minutes reperfusion) was significantly limited by A
1
AR KO, with impaired contractile recovery (reduced by ≈25%) and enhanced lactate dehydrogenase (LDH) efflux (increased by ≈100%). Functional effects of A
1
AR KO involved worsened systolic pressure development with little to no change in diastolic dysfunction. In contrast, cardiac specific A
1
AR overexpression enhanced ischemic tolerance with a primary action on diastolic dysfunction. Nonselective receptor agonism (10 μmol/L 2-chloroadenosine) protected wild-type and also A
1
AR KO hearts (albeit to a lesser extent), implicating protection via subtypes additional to A
1
ARs. However, A
1
AR KO abrogated effects of 2-chloroadenosine on ischemic contracture and diastolic dysfunction. These data are the first demonstrating global deletion of the A
1
AR limits intrinsic myocardial resistance to ischemia. Data indicate the function of intrinsically activated A
1
ARs appears primarily to be enhancement of postischemic contractility and limitation of cell death.
Land Preservation: An Essential Ingredient in Smart Growth
Authors: Daniels Tom , Lapping Mark
Published: January 2005

The preservation of land for working rural landscapes, wildlife habitat, urban parks, recreational trails, and protecting water supplies and floodplains is emerging as an integral component of smart growth programs. Both the general public and nonprofit organizations have been willing to spend billions of dollars on land preservation because of a perception that traditional land use planning and regulation are not successfully accommodating growth or protecting valuable natural resources. The literature on smart growth has largely overlooked the potential of land preservation to curb sprawl and to foster livable communities. The literature on land preservation has focused on the mechanics of conservation easements and land purchases rather than on how land preservation can fit in the comprehensive planning process to achieve community smart growth goals. More research needs to be done on the strategic use of land preservation in shaping and directing growth as part of a comprehensive planning effort.
What Is “Smart Growth?”—Really?
Authors: Ye Lin , Mandpe Sumedha , Meyer Peter B.
Published: January 2005

A“smart growth” agenda has been adopted by many different organizations. The label thus may have lost any clear-cut meaning due to the divergent perceptions and agendas of organizations using the term. Some appear to have adopted it as a form of political cover, whether for antigrowth or antiregulation positions. In other cases, the principles seem to be reformulated in response to the realities of local planning. This article first reviews smart growth statements from ten national organizations with divergent land use agendas. Despite their differing agendas, their broad conceptual definitions are found to converge. Turning to implementation efforts, the article then reviews forty-nine documents from two states: Georgia and Kentucky. The documents exhibit extreme variety in the meanings ascribed to smart growth. Moreover, few of the plans and policies incorporate multiple interventions, which is a key dimension of the smart growth approach as described by the national groups.
The Role of Inner Ring Suburbs in Metropolitan Smart Growth Strategies
Authors: Lee Sugie , Leigh Nancey Green
Published: January 2005

Strengthening the effectiveness of metropolitan smart growth policies requires an understanding of the role and conditions of inner ring suburbs. Nevertheless, the issue of the deterioration of the inner ring suburbs has only recently received significant consideration by urban scholars and policy makers. In this article, the authors review the literature on metropolitan formation and the smart growth movement to critically assess how well it characterizes and explains the evolution of inner ring suburbs, as well as to emphasize the role that inner ring suburbs can play in metropolitan smart growth strategies. They next characterize the literature specifically focused on inner ring suburbs in terms of what it has to offer on defining such areas. After identifying the gaps in the literature, the authors offer a methodology for accurately defining inner ring suburbs and conclude with a discussion of policy for effectively addressing the socioeconomic needs of the inner ring suburbs within the context of metropolitan smart growth.
Loss of Hspa9b in zebrafish recapitulates the ineffective hematopoiesis of the myelodysplastic syndrome
Authors: Craven Sarah E. , French Dorothy , Ye Weilan , de Sauvage Frederic , Rosenthal Arnon
Published: January 2005

Myelodysplastic syndrome (MDS) comprises a heterogeneous group of oftenfatal hematopoietic stem cell disorders for which neither curative nor standard treatment exists. The complex karyotypes and multistep nature of MDS have severely restricted the identification of causative genetic mutations and thus limited insight into new and more effective therapies. Here we describe a zebrafish mutant crimsonless (crs) with a developmental blood defect that closely recapitulates the ineffective hematopoiesis of MDS including anemia, dysplasia, increased blood cell apoptosis, and multilineage cytopenia. By positional cloning, rescue, and morpholino knockdown experiments, we demonstrate that crs encodes a conserved mitochondrial matrix chaperone HSPA9B containing a glycine-to-glutamate substitution within the substrate-binding domain. This mutation compromises mitochondrial function, producing oxidative stress and apoptosis distinctly in blood cells. Thus, we identify an essential role for Hspa9b in hematopoiesis and implicate both loss of HSPA9B specifically and mitochondrial dysfunction generally in the pathogenesis of the MDS.
Fc receptor γ-chain activation via hOSCAR induces survival and maturation of dendritic cells and modulates Toll-like receptor responses
Authors: Merck Estelle , de Saint-Vis Blandine , Scuiller Mathieu , Gaillard Claude , Caux Christophe , Trinchieri Giorgio , Bates Elizabeth E. M.
Published: January 2005

We previously reported the characterization of human osteoclast-associated receptor (hOSCAR), a novel Fc receptor γ-chain (FcRγ)–associated receptor expressed by myeloid cells. Here we show that ligation of hOSCAR by specific antibodies promotes dendritic cell (DC) survival by an extracellular signal-regulated kinase (ERK)- and phosphatidylinositol 3-kinase (PI3K)–dependent pathway, linked to expression of the Bcl-2 and Bcl-xL antiapoptotic molecules. Crosslinking of hOSCAR leads to maturation of DCs, as demonstrated by up-regulation of maturation markers, decrease in dextran uptake capacity, and secretion of immunesystem effectors such as interleukin-8 (IL-8)/CXC chemokine ligand 8 (CXCL8), IL-12 p40, monocyte chemoattractant protein-1 (MCP-1)/chemokine receptor ligand 2 (CCL2) and macrophage-derived chemokine (MDC)/CCL22. Stimulation of hOSCAR acts in conjunction with the Toll-like receptor (TLR) ligands, lipopolysaccharide (LPS), R-848, and polyinosinic-polycytidylic acid (poly(I:C)), to increase the expression of maturation markers, and to modulate cytokine release. A PI3K-dependent up-regulation of IL-10 release is observed with all the TLR ligands used, whereas regulation of IL-12 production is variable depending on the TLR stimulated. hOSCAR engagement on DCs did not significantly increase the proliferation of naive T cells; however, when co-incubated with TLR ligands, an enhanced proliferation was observed. The percentage of interferon (IFN)–γ–producing T cells is decreased when hOSCAR engagement is combined with LPS stimulation. Altogether, these data suggest that hOSCAR may modulate the responses of both innate resistance and adaptive immunity.
Identification of a human B-cell/myeloid common progenitor by the absence of CXCR4
Authors: Hou Yong-Hao , Srour Edward F. , Ramsey Heather , Dahl Richard , Broxmeyer Hal E. , Hromas Robert
Published: January 2005

CXCR4 is a chemokine receptor required for hematopoietic stem cell engraftment and B-cell development. This study found that a small fraction of primitive CD34+/CD19+ B-cell progenitors do not express CXCR4. These CD34+/CD19+/CXCR4- cells were also remarkable for the relative lack of primitive myeloid or lymphoid surface markers. When placed in B-lymphocyte culture conditions these cells matured to express CXCR4 and other surface antigens characteristic of B cells. Surprisingly, when placed in a myeloid culture environment, the CXCR4- B-cell progenitors could differentiate into granulocyte, macrophage, and erythroid cells at a high frequency. These data define a novel B-cell/myeloid common progenitor (termed the BMP) and imply a less restrictive pathway of myeloid versus lymphoid development than previously postulated.
Molecular modification of idiotypes from B-cell lymphomas for expression in mature dendritic cells as a strategy to induce tumor-reactive CD4+ and CD8+ T-cell responses
Authors: Muraro Sara , Bondanza Attilio , Bellone Matteo , Greenberg Philip D. , Bonini Chiara
Published: January 2005

Most non-Hodgkin B-cell lymphomas (NHLs) are characterized by the clonal expansion of a single cell expressing a unique rearranged immunoglobulin gene. This idiotype (Id) is a tumor-specific antigen that can be immunologically targeted. The therapeutic efficacy of Id-based vaccines correlates best with detection of cellular immune responses, although these have not been as well characterized as the humoral responses. This study exploited a molecular approach to modify the Id of 38C13 lymphoma for processing via class I and II antigen-processing pathways and evaluated protein expression in dendritic cells (DCs) to simultaneously stimulate tumor reactive CD8+ and CD4+ lymphocytes. Recombinant vaccinia viruses (rVVs) were constructed, coding for Id fused with the targeting signal of the lysosomal-associated membrane protein1 (Id-LAMP1) to promote antigen presentation in the context of major histocompatibility complex (MHC) class II. Mature DCs infected with rVV/Id-LAMP1 elicited both CD4+ and CD8+ Id-specific T cells and protected animals from tumor challenge. Id-specific CD8+ cells were required to mediate the effector phase of a therapeutic response, and CD4+ cells were beneficial in the induction phase of the response. These results demonstrate that fusing Id to LAMP1 enhances CD8+ and CD4+ Id-specific responses for NHLs and may be useful therapeutically.
Proteomic analysis of mantle-cell lymphoma by protein microarray
Authors: Ghobrial Irene M. , McCormick Daniel J. , Kaufmann Scott H. , Leontovich Alexey A. , Loegering David A. , Dai Nga T. , Krajnik Kelly L. , Stenson Mary J. , Melhem Mona F. , Novak Anne J. , Ansell Stephen M. , Witzig Thomas E.
Published: January 2005

Mantle-cell lymphoma (MCL) is a unique subtype of B-cell non-Hodgkin lymphoma (NHL) that behaves aggressively and remains incurable. In order to understand the pathogenesis of MCL and design new therapies, it is important to accurately analyze molecular changes in pathways dysregulated in MCL. We used antibody microarrays to compare patterns of protein expression between CD19+ purified B lymphocytes from normal tonsil and 7 cases of histologically confirmed MCL. Protein overexpression was defined as a higher than 1.3-fold or 2-fold increase in at least 67% of tumor samples compared with normal B-cell control. Of the polypeptides, 77 were overexpressed using the higher than 1.3-fold cutoff, and 13 were overexpressed using the 2-fold cutoff. These included cell cycle regulators (regulator of chromosome condensation 1 [RCC1], murine double minute 2 [MDM2]), a kinase (citron Rho-interacting kinase [CRIK]), chaperone proteins (heat shock 90-kDa protein [Hsp90], Hsp10), and phosphatase regulators (A-kinase anchor protein 1 [AKAP149], protein phosphatase 5 [PP5], and inhibitor 2). The elevated expression of some of these polypeptides was confirmed by immunoblotting and immunohistochemistry, whereas elevated expression of others could not be confirmed, illustrating the importance of confirmatory studies. This study describes a novel technique that identifies proteins dysregulated in MCL.
Jagged2 promotes the development of natural killer cells and the establishment of functional natural killer cell lines
Authors: DeHart Sarah L. , Heikens Marc J. , Tsai Schickwann
Published: January 2005

Emerging evidence indicates that Notch receptors and their ligands play important roles in the development of T cells and B cells. However, little is known about their possible roles in the development of other lymphoid cells. Here we demonstrate that Jagged2, a Notch ligand, stimulates the development of natural killer (NK) cells from Lin- Sca-1+ c-kit+ hematopoietic stem cells. Our culture system supports NK cell development for 2 to 3 months, often leading to the establishment of continuous NK cell lines. The prototype of such cell lines is designated as KIL. KIL depends on interleukin-7 for survival and proliferation and is NK1.1+ CD3- TCRαβ- TCRδγ- CD4- CD8- CD19- CD25+ CD43+ CD45+ CD49b- CD51+ CD94+ NKG2D+ Mac-1-/low B220- c-kit+ perforin I+ granzyme B+ Notch-1+, and cytotoxic. Like normal natural killer cells, the T-cell receptor-β loci of KIL remain in the germ-line configuration. In response to interleukin-2, KIL proliferates extensively (increasing cell number by approximately 1010-fold) and terminally differentiates into adherent, hypergranular NK cells. Our findings indicate that Jagged2 stimulates the development of natural killer cells and the KIL cell line preserves most properties of the normal NK precursors. As such, KIL provides a valuable model system for NK cell research.