bluuebunny/crossref_metadata_2025 huggingface dataset:
Graptolites from the Laforce and St. Léon Formations, Northern Gaspé, Quebec
Authors: Lenz Alfred C.
Published: April 2010

Graptolites described from the Laforce Formation include Monograptus priodon, Pristiograptus bohemicus bohemicus, P. dubius cf. P. dubius thuringicus, and Saetograptus? colonus compactus. A Wenlockian to early Ludlovian age is indicated. St. Léon Formation graptolites include Lobograptus? scanicus, Monoclimacis micropoma, Pristiograptus bohemicus bohemicus, and Saetograptus? colonus compactus, of Ludlovian age, and Monograptus ex. gr. microdon, M. praehercynicus, Pristiograptus aequabilis aequabilis, and Linograptus posthumus posthumus of Early Devonian, probably Gedinnian, age.A new subspecies Pristiograptus aequabilis gaspesiensis of early Devonian age is described from the St. Léon Formation of the Lesseps Brook locality.
Nd isotopic evidence for crustal recycling in the ca. 2.0 Ga subsurface of western Canada
Authors: Thériault R. J. , Ross G. M.
Published: April 2010

Sm–Nd isotopic data are presented for 23 drill-core samples from five aeromagnetically and geochronologically (U–Pb zircon) distinct domains of the Precambrian basement of northern Alberta. The domains in question are the Taltson (1.96–1.94 Ga), Buffalo Head (2.32–1.99 Ga), Chinchaga (2.19–2.09 Ga), Ksituan (1.99–1.90 Ga), and Nova (2.81 Ga). These domains are truncated to the north and south by the Great Slave Lake shear zone and the Snowbird tectonic zone, respectively.Initial εNd values are −5.0 to −9.7 for the Taltson, +0.2 to −6.3 for the Buffalo Head, +0.6 to −1.8 for the Chinchaga, −1.8 to −2.1 for the Ksituan and +5.6 for the Nova. Crustal residence model ages fall in the 2.5–2.8 Ga range. The Nd isotopic signatures may be viewed in terms of mixing a minimum of 10% Archean continental crust with a depleted-mantle component. Speculations on the tectonic history of the basement domains in question involve the assembly of Archean crustal nuclei to form the Buffalo Head – Chinchaga composite domain. Arc magmatism resulting from plate subduction to the east and west of the Buffalo Head – Chinchaga composite domain would have generated the Taltson and Ksituan domains. The Nd isotopic data suggest that the basement of northern Alberta consists of crust of late Archean crustal residence age which has been extensively remobilized in the Early Proterozoic.
Proterozoic craton to basin crustal transition in western Canada and its influence on the evolution of the Cordillera
Authors: Cook Frederick A. , Varsek John L. , Clark Elizabeth A.
Published: April 2010

Deep seismic reflection data have imaged a crustal-scale, west-facing ramp or ramp system in the subsurface of western Canada. In northwestern Canada the ramp is within Proterozoic crust east of the Cordillera and is unconformably overlain by Paleozoic sedimentary rocks, indicating that it was formed during the Proterozoic in this region. Similar structures are visible within the Cordillera in southern Canada and the northwestern United States along a south projection of the ramp observed in the north. In the Monashee Complex of British Columbia and in the Priest River Complex in northern Washington, reflections are visible that dip westward from the surface to near the base of the crust and are structurally discordant with underlying more horizontal reflections, thus outlining footwall ramps. We propose that the Proterozoic crustal ramp in the north and the footwall ramps in the Cordillera probably coincide with a Proterozoic crustal transition from thick craton on the east to thin crust on the west. This transition may have influenced sedimentation patterns during deposition of Middle Proterozoic Belt–Purcell and Wernecke strata (ca. 1.6–1.3 Ga) and probably controlled the arcuate shape of the Mackenzie Mountains during their formation in the Mesozoic. This interpretation is consistent with the notion that thrust sheets of the Mackenzie Mountains did not extend onto the craton a sufficient distance to produce flexural subsidence of the thick crust and associated foreland basin development, whereas thrust sheets of the southern Canadian Cordillera were driven eastward and loaded the thick craton, causing crustal flexure and development of the Alberta Basin.
Age and isotopic character of Early Proterozoic basement gneisses in the southern Monashee Complex, southeastern British Columbia
Authors: Parkinson Dave
Published: April 2010

The southern Monashee Complex is a fault-bounded exposure of upper-amphibolite-grade basement gneisses (core gneisses) and unconformably overlying mantling metasedimentary gneisses. The eastern margin is marked by the Early Eocene ductile to brittle Columbia River fault zone; the western and southern margins are marked by the Monashee Decollement and structurally higher Selkirk allochthon.The basement gneisses are exposed in the cores of large, northeast-verging nappes that subsequently have been overprinted towards the east by the Columbia River fault zone. The basement gneisses are a supracrustal sequence intruded by at least two distinct orthogneisses: (i) a biotite granite gneiss ("gray gneiss") dated by U/Pb zircon at 1874 ± 21 Ma; and (ii) a ±hornblende–biotite K-feldspar augen gneiss dated by U/Pb zircon at 1934 ± 6 Ma.The supracrustal gneisses are predominantly heterogeneous biotite–quartz–feldspar gneiss interlayered with less common pelitic schist and calc-silicate gneiss. U/Pb zircon data on detrital zircon populations from this heterogeneous supracrustal sequence give 207Pb*/206Pb* ages of less than 2.2 Ga. Whole-rock Pb isotopic data indicate an age of approximately 2.0 Ga. Whole-rock Sm/Nd model ages on the two intrusive suites indicate separate sources, the 1874 Ma gneiss having been produced from similar-age juvenile Early Proterozoic material (TDM ≈ 2.2 Ga). In contrast, Nd data from the 1934 Ma augen gneiss clearly indicate interaction with a component of older (late Archean) material (TDM ≈ 2.8 Ga). Whole-rock Sm/Nd data from the supracrustal gneisses follow this same pattern, with one group (seven samples) similar to the 1874 Ma gneiss (with TDM ≈ 2.3–2.6 Ga) and a second group (five samples) showing provenance or derivation from an Archean source (TDM = 2.8–3.3 Ga). The age of the intrusive suites, combined with the Nd data, strongly argues for a correlation with the Early Proterozoic Wopmay orogenic belt in northern Canada.
Detrital zircon geochronology of metasedimentary rocks in the southern Omineca Belt, Canadian Cordillera
Authors: Ross Gerald M. , Parrish Randall R.
Published: April 2010

We address two problems of Cordilleran geology in this study using U–Pb dating of single detrital zircon grains from metasedimentary rocks: the provenance of the Windermere Supergroup, and the age and correlation of metasedimentary rocks within the Shuswap Complex that are at high metamorphic grade. Because some of these rocks are clearly of North American affinity, the ages of zircons provide indirect constraints on the age and distribution of continental basement from which the zircons were derived.A consistent pattern emerges from ages of about 50 grains from six rocks. Nearly all samples analyzed (48–53°N) are characterized by a bimodal distribution of zircon ages of 1.65–2.16 Ga and > 2.5 Ga, with a distinct lack of ages between 2.1 and 2.5 Ga. Exceptions to this pattern are young zircons from two samples, from Valhalla and Grand Forks – Kettle complexes of southeastern British Columbia, that have grains 1435 ± 35 and 650 ± 15 Ma, respectively. These younger grains are inferred to have been derived from magmatic rocks, and they have no obvious source in either the Canadian Shield or the Alberta subsurface basement to the east. The Early Proterozoic and Archean ages of detrital zircons resemble those of dated basement rocks beneath the Alberta Basin as well as basement exposed within the Cordilleran hinterland (gneisses of Thor–Odin, Frenchman Cap, and Malton regions). However, 2.1–2.4 Ga rocks that are extensive in the subsurface of northern Alberta are not represented in the inventory of detrital zircon ages presented in this paper.This pattern suggests that much of the Cordilleran basement between these latitudes is underlain by Archean crust of the Hearne–Wyoming provinces that may be mantled to the west by an orogenic–magmatic belt of Early Proterozoic (1.7–1.9 Ga) age which may largely have been parallel to the present Cordilleran orogen.
Detrital zircon geochronology of Upper Proterozoic to lower Paleozoic continental margin strata of the Kootenay Arc: implications for the early Paleozoic tectonic development of the eastern Canadian Cordillera
Authors: Smith Moira T. , Gehrels George E.
Published: April 2010

The Kootenay Arc in northeastern Washington and southeastern British Columbia contains the transition between autochthonous Upper Proterozoic to lower Paleozoic miogeoclinal strata and outboard Paleozoic to Mesozoic eugeoclinal terranes of uncertain paleogeographic affinity. To better understand the nature of this transition, U–Pb detrital zircon geochronologic studies were carried out on Upper Proterozic and lower Paleozoic sedimentary units in the Kootenay Arc, including miogeoclinal strata of the Horsethief Creek and Hamill groups and eugeoclinal strata of the Broadview and Ajax formations (Lardeau Group) and Daisy Formation (Covada Group). The results indicate that all units sampled are derived from source terranes of ~1.7 to 2.7 Ga, with notable populations of 1.76–1.85, 1.9–2.1, and 2.5–2.7 Ga zircons. These results are consistent with derivation of both the miogeoclinal and lower Paleozoic eugeoclinal units from adjacent portions of the southern Alberta craton. This extends the western limit of supracrustal rocks of known North American affinity, formed approximately in situ in the southern Canadian Cordillera, to outboard of the lower Paleozoic eugeoclinal strata in the Kootenay Arc.
U–Pb geochronology of detrital zircons from a continental margin assemblage in the northern Coast Mountains, southeastern Alaska
Authors: Gehrels George E. , McClelland William C. , Samson Scott D. , Patchett P. Jonathan
Published: April 2010

Metamorphic rocks within and west of the northern Coast Mountains in southeastern Alaska consist of an Upper Proterozoic(?) to upper Paleozoic continental margin assemblage that we interpret to belong to the Yukon-Tanana terrane. U–Pb geochronologic analyses of single detrital zircon grains from four samples of quartzite suggest that the zircons were shed from source regions containing rocks of ~495 Ma, ~750 Ma, 1.05–1.40 Ga, 1.75–2.00 Ga, ~2.3 Ga, 2.5–2.7 Ga, and ~3.0 Ga. Multigrain fractions from two samples yield upper intercepts between 2.0 and 2.3 Ga, but the scarcity of single grains of similar age suggests that these fractions comprise a mixture of < 2.0 and > 2.3 Ga grains. Zircons in these rocks generally overlap in age with (i) detrital zircons in metasedimentary rocks of the Yukon–Tanana terrane in eastern Alaska and Yukon, (ii) detrital zircons in strata of the Cordilleran miogeocline, and (iii) plutonic and gneissic rocks that intrude or are overlain by miogeoclinal strata. In addition, the pre-1.7 Ga grains overlap in age with dated crystalline rocks of the western Canadian Shield. These similarities raise the possibility that metaclastic rocks in the northern Coast Mountains accumulated in proximity to western North America. The younger zircon populations were likely shed from mid-Proterozoic to early Paleozoic igneous rocks that now occur locally (but may have been widespread) along the Cordilleran margin. Recognition of a continental margin assemblage of possible North American affinity in the Coast Mountains raises the possibility that some arc-type and oceanic terranes inboard of the Coast Mountains may be large klippen that have been thrust over the North American margin.
SCALE TESTING IN SMALL SAMPLES WITH MISSING TIME-TO-FAILURE INFORMATION
Authors: STEHLÍK MILAN
Published: April 2010

We provide the exact likelihood ratio testing procedure of the scale parameter of the Erlang and gamma distribution when there is a missing time-to-failure information. This is an important result because the asymptotical χ2-test is oversized an thus inappropriate especially for small merged samples. The small merged samples can arise also for a large sample sizes, e.g. when individual times-to-failure are not available. Data sets with missing time-to-failure data can arise from field data collection systems. Real data and simulated examples are provided to illustrate the methods discussed.
REINFORCEMENT OF POWER SYSTEM RELIABILITY MEASURES THROUGH JOINT DETERMINISTIC AND PROBABILISTIC APPROACHES
Authors: VENU V. VIJAY , VERMA A. K.
Published: April 2010

By adapting the emerging conceptualization of reliability network equivalents, originally developed to obtain reliability indices in the restructured scenario, a suitable framework encapsulating relatively independent modularity could be evolved that shall enable the application of joint deterministic- probabilistic well being-analysis for the composite restructured power systems. Reliability management forms the core component of successful transition from vertical integration of power systems to their deregulation. Timely reinforcements to the resource adequacy will ensure reliably operating power systems. Redundancy apportioning without pessimistic appraisals or exceedingly optimistic estimates is a vital ingredient for the success of restructured systems. With these goals in mind, this paper puts forward a philosophical modeling paradigm that investigates the feasibility of extending the hybrid approach of well-being analysis to a composite bilateral contracts market structure, a potential indicator of generation reinforcements to gear up for. Probabilistic load flow studies as a means to justify transmission reinforcements is also brought forward. Also presented is an overview of the reliability cost-worth methods, information from which forms an integral part of the reinforcement strategies.
GENERAL FRAMEWORK FOR CHANGE POINT PROBLEM IN SOFTWARE RELIABILITY AND RELATED RELEASE TIME PROBLEM
Authors: KAPUR P. K. , GARG R. B. , AGGARWAL ANU. G. , TANDON ABHISHEK
Published: April 2010

Reliable software is the need of the hour especially as it is an indispensable part of our new technological world. Many SRGMs have been proposed considering the change point approach in literature. Change point is defined as the point where the fault detection rate changes, it happens due to number of reasons viz, proficiency of the testing team, nature of faults to be detected etc. In this paper we develop a generalized modeling framework incorporating change point discussing the changing nature of fault detection rate and form a related release time problem which minimizes the total cost of the software and maintains a desirable level of reliability. A numerical example is given for the release problem and the proposed models are validated on real software error data to show their goodness of fit and applicability.
NATURAL LANGUAGE SPECIFICATION IMPROVEMENT WITH ONTOLOGIES
Authors: KÖRNER SVEN J. , BRUMM TORBEN
Published: April 2010

Requirements engineering can solve and cause many problems in a software development cycle. The difficulties in understanding and eliciting the desired functionality from the customer and then delivering the correct implementation of a software system lead to delays, mistakes, and high costs. Working with requirements means handling incomplete or faulty textual specifications. It is vital for a project to fully understand the purpose and the functionality of a software. The earlier specifications are corrected and improved, the better. We created a tool called RESI to support requirement analysts working with textual specifications. RESI checks for linguistic defects [1, 2] in specifications and offers a dialog-system which makes suggestions to improve the text. It points out to the user which parts of the specification are ambiguous, faulty or inaccurate and therefore need to be changed. For this task, RESI needs additional semantic information which is inherent to natural language specifications. It receives this information by utilizing ontologies.
TOWARDS A SEMANTIC STATE TRANSITION SYSTEM FOR AUTOMATED GENERATION OF DATA FLOW IN WEB SERVICE COMPOSITION
Authors: LÉCUÉ FREDDY , DELTEIL ALEXANDRE , LÉGER ALAIN
Published: April 2010

Most of the work on automated web service composition has focused so far on composition of stateful web services. This level of composition so-called "Process Level" considers web services with their internal and complex behaviors. At process level formal models such as State Transition Systems (STS from now) or Interface Automata are the most appropriate models to represent the internal behavior of stateful web services. However such models focus only on semantics of their behaviors and unfortunately not on semantics of actions and their parameters. In this paper, we suggest to extend the STS model, by following the WSMO based annotation for Abstract State Machine. This semantic enhancement of STS so called S2 TS will enable to model semantics of internal behaviors and semantics of their actions together with their input and output parameters. Secondly, we will focus on automated generation of data flow (or the process to perform automated assignments between parameter of services involved in a composition). Thus we do not restrict to assignments of exact parameters (which is practically never used in industrial scenario) but extend assignments to semantically close parameters (e.g., through a subsumption matching) in the same ontology. Our system is implemented and interacting with web services dedicated to Telecommunication scenarios. The preliminary evaluation results showed high efficiency and effectiveness of the proposed approach.
MAPPING VERBAL ARGUMENT PREFERENCES TO DEVERBAL NOUNS
Authors: GUREVICH OLGA , WATERMAN SCOTT A.
Published: April 2010

We describe an experiment mapping semantic role preferences for transitive verbs to their deverbal nominal forms. The preferences are learned by data mining large parsed corpora. Preferences are modeled for deverbal/argument pairs, falling back to a model for the deverbal only when sufficient data is not available. Errors in role assignment are reduced by 30–40%.
Neutrophils exposed to A. phagocytophilum under shear stress fail to fully activate, polarize, and transmigrate across inflamed endothelium
Authors: Schaff U. Y. , Trott K. A. , Chase S. , Tam K. , Johns J. L. , Carlyon J. A. , Genetos D. C. , Walker N. J. , Simon S. I. , Borjesson D. L.
Published: April 2010

Anaplasma phagocytophilum is an obligate intracellular bacterium that has evolved mechanisms to hijack polymorphonuclear neutrophil (PMN) receptors and signaling pathways to bind, infect, and multiply within the host cell. E-selectin is upregulated during inflammation and is a requisite endothelial receptor that supports PMN capture, rolling, and activation of integrin-mediated arrest. Ligands expressed by PMN that mediate binding to endothelium via E-selectin include sialyl Lewis x (sLex)-expressing ligands such as P-selectin glycoprotein ligand-1 (PSGL-1) and other glycolipids and glycoproteins. As A. phagocytophilum is capable of binding to sLex-expressing ligands expressed on PMN, we hypothesized that acute bacterial adhesion to PMN would subsequently attenuate PMN recruitment during inflammation. We assessed the dynamics of PMN recruitment and migration under shear flow in the presence of a wild-type strain of A. phagocytophilum and compared it with a strain of bacteria that binds to PMN independent of PSGL-1. Acute bacterial engagement with PMN resulted in transient PMN arrest and minimal PMN polarization. Although the wild-type pathogen also signaled activation of β2 integrins and elicited a mild intracellular calcium flux, downstream signals including PMN transmigration and phosphorylation of p38 mitogen-activated protein kinase (MAPK) were inhibited. The mutant strain bound less well to PMN and failed to activate β2 integrins and induce a calcium flux but did result in decreased PMN arrest and polarization that may have been partially mediated by a suppression of p38 MAPK activation. This model suggests that A. phagocytophilum binding to PMN under shear flow during recruitment to inflamed endothelium interferes with normal tethering via E-selectin and navigational signaling of transendothelial migration.
Voltage-gated K+ channels sensitive to stromatoxin-1 regulate myogenic and neurogenic contractions of rat urinary bladder smooth muscle
Authors: Chen Muyan , Kellett Whitney F. , Petkov Georgi V.
Published: April 2010

Members of the voltage-gated K+ (KV) channel family are suggested to control the resting membrane potential and the repolarization phase of the action potential in urinary bladder smooth muscle (UBSM). Recent studies report that stromatoxin-1, a peptide isolated from tarantulas, selectively inhibits KV2.1, KV2.2, KV4.2, and KV2.1/9.3 channels. The objective of this study was to investigate whether KV channels sensitive to stromatoxin-1 participate in the regulation of rat UBSM contractility and to identify their molecular fingerprints. Stromatoxin-1 (100 nM) increased the spontaneous phasic contraction amplitude, muscle force, and tone in isolated UBSM strips. However, stromatoxin-1 (100 nM) had no effect on the UBSM contractions induced by depolarizing agents such as KCl (20 mM) or carbachol (1 μM). This indicates that, under conditions of sustained membrane depolarization, the KV channels sensitive to stromatoxin-1 have no further contribution to the membrane excitability and contractility. Stromatoxin-1 (100 nM) increased the amplitude of the electrical field stimulation-induced contractions, suggesting also a role for these channels in neurogenic contractions. RT-PCR experiments on freshly isolated UBSM cells showed mRNA expression of KV2.1, KV2.2, and KV9.3, but not KV4.2 channel subunits. Protein expression of KV2.1 and KV2.2 channels was detected using Western blot and was further confirmed by immunocytochemical detection in freshly isolated UBSM cells. These novel findings indicate that KV2.1 and KV2.2, but not KV4.2, channel subunits are expressed in rat UBSM and play a key role in opposing both myogenic and neurogenic UBSM contractions.
Regular exercise prevents the development of hyperglucocorticoidemia via adaptations in the brain and adrenal glands in male Zucker diabetic fatty rats
Authors: Campbell Jonathan E. , Király Michael A. , Atkinson Daniel J. , D'souza Anna M. , Vranic Mladen , Riddell Michael C.
Published: April 2010

We determined the effects of voluntary wheel running on the hypothalamic-pituitary-adrenal (HPA) axis, and the peripheral determinants of glucocorticoids action, in male Zucker diabetic fatty (ZDF) rats. Six-week-old euglycemic ZDF rats were divided into Basal, Sedentary, and Exercise groups ( n = 8–9 per group). Basal animals were immediately killed, whereas Sedentary and Exercising rats were monitored for 10 wk. Basal (i.e., ∼0900 AM in the resting state) glucocorticoid levels increased 2.3-fold by week 3 in Sedentary rats where they remained elevated for the duration of the study. After an initial elevation in basal glucocorticoid levels at week 1, Exercise rats maintained low glucocorticoid levels from week 3 through week 10. Hyperglycemia was evident in Sedentary animals by week 7, whereas Exercising animals maintained euglycemia throughout. At the time of death, the Sedentary group had ∼40% lower glucocorticoid receptor (GR) content in the hippocampus, compared with the Basal and Exercise groups ( P < 0.05), suggesting that the former group had impaired negative feedback regulation of the HPA axis. Both Sedentary and Exercise groups had elevated ACTH compared with Basal rats, indicating that central drive of the axis was similar between groups. However, Sedentary, but not Exercise, animals had elevated adrenal ACTH receptor and steroidogenic acute regulatory protein content compared with the Basal animals, suggesting that regular exercise protects against elevations in glucocorticoids by a downregulation of adrenal sensitivity to ACTH. GR and 11β-hydroxysteroid dehydrogenase type 1 content in skeletal muscle and liver were similar between groups, however, GR content in adipose tissue was elevated in the Sedentary groups compared with the Basal and Exercise ( P < 0.05) groups. Thus, the gradual elevations in glucocorticoid levels associated with the development of insulin resistance in male ZDF rats can be prevented with regular exercise, likely because of adaptations that occur primarily in the adrenal glands.
Food deprivation alters thermoregulatory responses to lipopolysaccharide by enhancing cryogenic inflammatory signaling via prostaglandin D2
Authors: Krall Catherine M. , Yao Xiujuan , Hass Martha A. , Feleder Carlos , Steiner Alexandre A.
Published: April 2010

We tested the hypothesis that food deprivation alters body temperature (Tb) responses to bacterial LPS by enhancing inflammatory signaling that decreases Tb (cryogenic signaling) rather than by suppressing inflammatory signaling that increases Tb (febrigenic signaling). Free-feeding or food-deprived (24 h) rats received LPS at doses (500 and 2,500 μg/kg iv) that are high enough to activate both febrigenic and cryogenic signaling. At these doses, LPS caused fever in rats at an ambient temperature of 30°C, but produced hypothermia at an ambient temperature of 22°C. Whereas food deprivation had little effect on LPS fever, it enhanced LPS hypothermia, an effect that was particularly pronounced in rats injected with the higher LPS dose. Enhancement of hypothermia was not due to thermogenic incapacity, since food-deprived rats were fully capable of raising Tb in response to the thermogenic drug CL316,243 (1 mg/kg iv). Neither was enhancement of hypothermia associated with altered plasma levels of cytokines (TNF-α, IL-1β, and IL-6) or with reduced levels of an anti-inflammatory hormone (corticosterone). The levels of PGD2 and PGE2 during LPS hypothermia were augmented by food deprivation, although the ratio between them remained unchanged. Food deprivation, however, selectively enhanced the responsiveness of rats to the cryogenic action of PGD2 (100 ng icv) without altering the responsiveness to febrigenic PGE2 (100 ng icv). These findings support our hypothesis and indicate that cryogenic signaling via PGD2 underlies enhancement of LPS hypothermia by food deprivation.
Lipid-induced insulin resistance is prevented in lean and obese myotubes by AICAR treatment
Authors: Bikman Benjamin T. , Zheng Donghai , Reed Melissa A. , Hickner Robert C. , Houmard Joseph A. , Dohm G. Lynis
Published: April 2010

The molecular mechanisms of obesity-associated insulin resistance are becoming increasingly clear, and the effects of various lipid molecules, such as diacylglycerol and ceramide, on the insulin signal are being actively explored. To better understand the divergent response to lipid exposure between lean and obese, we incubated primary human muscle cells from lean [body mass index (BMI) <25 kg/m2] and morbidly obese (BMI >40 kg/m2) subjects with the saturated fatty acid palmitate. Additionally, given that AMPK-activating drugs are widely prescribed for their insulin-sensitizing effects, we sought to determine whether 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR)-stimulated AMPK activation could prevent or reverse the deleterious effects of lipid on insulin signaling. We found that a 1-h palmitate incubation in lean myotubes reduced ( P < 0.05) insulin-stimulated phosphoprotein kinase B (Akt), Akt substrate 160 (AS160), and inhibitory factor κBα (IκBα) mass, all of which were prevented with AICAR inclusion. With a longer incubation, we observed that myotubes from morbidly obese individuals appear to be largely resistant to the detrimental effects of 16 h lipid exposure as was evident, in contrast to the lean, by the absence of a reduction in insulin-stimulated insulin receptor substrate (IRS)-1 Tyr phosphorylation, phospho-Akt, and phospho-AS160 ( P < 0.05). Furthermore, 16 h lipid exposure significantly reduced IκBα levels and increased phosphorylation of c-Jun NH2-terminal kinase (JNK) and IRS1-Ser312 in lean myotubes only ( P < 0.05). Despite a divergent response to lipid between lean and obese myotubes, AICAR inclusion improved insulin signaling in all myotubes. These findings suggest an important role for regular exercise in addition to offering a potential mechanism of action for oral AMPK-activating agents, such as thiazolidinediones and metformin.
Aging and its effects on inflammation in skeletal muscle at rest and following exercise-induced muscle injury
Authors: Peake Jonathan , Gatta Paul Della , Cameron-Smith David
Published: April 2010

The world's elderly population is expanding rapidly, and we are now faced with the significant challenge of maintaining or improving physical activity, independence, and quality of life in the elderly. Counteracting the progressive loss of muscle mass that occurs in the elderly, known as sarcopenia, represents a major hurdle in achieving these goals. Indirect evidence for a role of inflammation in sarcopenia is that markers of systemic inflammation correlate with the loss of muscle mass and strength in the elderly. More direct evidence is that compared with skeletal muscle of young people, the number of macrophages is lower, the gene expression of several cytokines is higher, and stress signaling proteins are activated in skeletal muscle of elderly people at rest. Sarcopenia may also result from inadequate repair and chronic maladaptation following muscle injury in the elderly. Macrophage infiltration and the gene expression of certain cytokines are reduced in skeletal muscle of elderly people compared with young people following exercise-induced muscle injury. Further research is required to identify the cause(s) of inflammation in skeletal muscle of elderly people. Additional work is also needed to expand our understanding of the cells, proteins, and transcription factors that regulate inflammation in the skeletal muscle of elderly people at rest and after exercise. This knowledge is critical for devising strategies to restrict sarcopenia, and improve the health of today's elderly population.
Basal adrenergic tone is required for maximal stimulation of rat brown adipose tissue UCP1 expression by chronic PPAR-γ activation
Authors: Festuccia William T. , Blanchard Pierre-Gilles , Richard Denis , Deshaies Yves
Published: April 2010

We investigated the involvement of basal sympathetic tone in brown adipose tissue (BAT) recruitment and gene expression profile induced by peroxisome proliferator-activated receptor-γ (PPAR-γ) activation. Innervated and surgically denervated BAT pads of rats treated or not with rosiglitazone (15 mg·kg−1·day−1, 7 days) were evaluated for weight, triacylglycerol (TAG) and DNA content, mitochondrial mass, and gene expression. Rosiglitazone induced BAT recruitment (increased mass, TAG and DNA content) and mRNA levels of lipolytic (adipose tissue triglyceride lipase and CGI58) and lipogenic (lipoprotein lipase, phosphoenolpyruvate carboxykinase, fatty acid binding protein 4, and diacylglycerol acyltransferase 1) proteins independently of tissue innervation status. Mitochondrial mass and mRNA levels of its regulators peroxisome proliferator-activated receptor coactivator-α and CCAAT/enhancer binding protein-β were not affected by rosiglitazone, while being significantly reduced by denervation. By contrast, maximal stimulation of uncoupling protein 1 (UCP1) (thermogenesis), cell death-inducing DNA fragmentation factor-45-like effector A (inhibitor of UCP1 activity), monoacylglycerol lipase (lipolysis), small heterodimer partner (transcription), and glycerokinase (TAG synthesis) by rosiglitazone depended on the presence of intact BAT innervation. Cold exposure (5°C, 24 h) significantly increased UCP1 mRNA levels in innervated BAT pads of untreated rats, without affecting the already high BAT UCP1 levels of rosiglitazone-treated animals. A similar pattern of response was found in denervated pads, but with markedly lower UCP1 expression than that in innervated BAT. In conclusion, whereas the mass (hyperplasia and hypertrophy), lipogenic, and lipolytic components of BAT recruitment induced by rosiglitazone occur independently of tissue sympathetic innervation, maximal UCP1 expression induced by PPAR-γ in vivo depends on the presence of basal BAT adrenergic tone. The residual sympathetic tone found under rosiglitazone treatment is, therefore, involved in the modulation of a subset of major components of PPAR-γ-mediated BAT recruitment.
RasGRP1 stimulation enhances ubiquitination and endocytosis of the sodium-chloride cotransporter
Authors: Ko Benjamin , Kamsteeg Erik-Jan , Cooke Leslie L. , Moddes Lauren N. , Deen Peter M. T. , Hoover Robert S.
Published: April 2010

The sodium-chloride cotransporter (NCC) is the principal salt-absorptive pathway in the distal convoluted tubule. Recently, we described a novel pathway of NCC regulation in which phorbol esters (PE) stimulate Ras guanyl-releasing protein 1 (RasGRP1), triggering a cascade ultimately activating ERK1/2 MAPK and decreasing NCC cell surface expression (Ko B, Joshi LM, Cooke LL, Vazquez N, Musch MW, Hebert SC, Gamba G, Hoover RS. Proc Natl Acad Sci USA 104: 20120–20125, 2007). Little is known about the mechanisms which underlie these effects on NCC activity. Regulation of NCC via changes in NCC surface expression has been reported, but endocytosis of NCC has not been demonstrated. In this study, utilizing biotinylation, internalization assays, and a dynamin dominant-negative construct, we demonstrate that the regulation of NCC by PE occurs via an enhancement in internalization of NCC and is dynamin dependent. In addition, immunoprecipitation of NCC and subsequent immunoblotting for ubiquitin showed increased ubiquitination of NCC with phorbol ester treatment. MEK1/2 inhibitors and gene silencing of RasGRP1 indicated that this effect was dependent on RasGRP1 and ERK1/2 activation. Inhibition of ubiquitination prevents any PE-mediated decrease in NCC surface expression as measured by biotinylation or NCC activity as measured by radiotracer uptake. These findings confirmed that the PE effect on NCC is mediated by endocytosis of NCC. Furthermore, ubiquitination of NCC is essential for this process and this ubiquitination is dependent upon RasGRP1-mediated ERK1/2 activation.
Localization of members of MCT monocarboxylate transporter family Slc16 in the kidney and regulation during metabolic acidosis
Authors: Becker Helen M. , Mohebbi Nilufar , Perna Angelica , Ganapathy Vadivel , Capasso Giovambattista , Wagner Carsten A.
Published: April 2010

The monocarboxylate transporter family (MCT) comprises 14 members with distinct transport properties and tissue distribution. The kidney expresses several members of the MCT family, but only little is known about their exact distribution and function. Here, we investigated selected members of the MCT family in the mouse kidney. MCT1, MCT2, MCT7, and MCT8 localized to basolateral membranes of the epithelial cells lining the nephron. MCT1 and MCT8 were detected in proximal tubule cells whereas MCT7 and MCT2 were located in the thick ascending limb and the distal tubule. CD147, a β-subunit of MCT1 and MCT4, showed partially overlapping expression with MCT1 and MCT2. However, CD147 was also found in intercalated cells. We also detected SMCT1 and SMCT2, two Na+-dependent monocarboxylate cotransporters, on the luminal membrane of type A intercalated cells. Moreover, mice were given an acid load for 2 and 7 days. Acidotic animals showed a marked but transient increase in urinary lactate excretion. During acidosis, a downregulation of MCT1, MCT8, and SMCT2 was observed at the mRNA level, whereas MCT7 and SMCT1 showed increased mRNA abundance. Only MCT7 showed lower protein abundance whereas all other transporters remained unchanged. In summary, we describe for the first time the localization of various MCT transporters in mammalian kidney and demonstrate that metabolic acidosis induces a transient increase in urinary lactate excretion paralleled by lower MCT7 protein expression.
Detrusor overactivity is associated with downregulation of large-conductance calcium- and voltage-activated potassium channel protein
Authors: Chang Shaohua , Gomes Cristiano Mendes , Hypolite Joseph A. , Marx James , Alanzi Jaber , Zderic Stephen A. , Malkowicz Bruce , Wein Alan J. , Chacko Samuel
Published: April 2010

Large-conductance voltage- and calcium-activated potassium (BK) channels have been shown to play a role in detrusor overactivity (DO). The goal of this study was to determine whether bladder outlet obstruction-induced DO is associated with downregulation of BK channels and whether BK channels affect myosin light chain 20 (MLC20) phosphorylation in detrusor smooth muscle (DSM). Partial bladder outlet obstruction (PBOO) was surgically induced in male New Zealand White rabbits. The rabbit PBOO model shows decreased voided volumes and increased voiding frequency. DSM from PBOO rabbits also show enhanced spontaneous contractions compared with control. Both BK channel α- and β-subunits were significantly decreased in DSM from PBOO rabbits. Immunostaining shows BKβ mainly expressed in DSM, and its expression is much less in PBOO DSM compared with control DSM. Furthermore, a translational study was performed to see whether the finding discovered in the animal model can be translated to human patients. The urodynamic study demonstrates several overactive DSM contractions during the urine-filling stage in benign prostatic hyperplasia (BPH) patients with DO, while DSM is very quiet in BPH patients without DO. DSM biopsies revealed significantly less BK channel expression at both mRNA and protein levels. The degree of downregulation of the BK β-subunit was greater than that of the BK α-subunit, and the downregulation of BK was only associated with DO, not BPH. Finally, the small interference (si) RNA-mediated downregulation of the BK β-subunit was employed to study the effect of BK depletion on MLC20phosphorylation. siRNA-mediated BK channel reduction was associated with an increased MLC20phosphorylation level in cultured DSM cells. In summary, PBOO-induced DO is associated with downregulation of BK channel expression in the rabbit model, and this finding can be translated to human BPH patients with DO. Furthermore, downregulation of the BK channel may contribute to DO by increasing the basal level of MLC20phosphorylation.
Expression of ammonia transporter family members, Rh B glycoprotein and Rh C glycoprotein, in the developing rat kidney
Authors: Han Ki-Hwan , Lee Su-Youn , Kim Wan-Young , Shin Jung-A , Kim Jin , Weiner I. David
Published: April 2010

Ammonia metabolism is a primary component of acid-base homeostasis but is incompletely developed at time of birth. Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg) are recently recognized ammonia transporter family members expressed in the mammalian kidney. This study's purpose was to establish the expression and localization of Rhbg and Rhcg during kidney development. We examined kidneys from fetal days 16 ( E16), 18 ( E18), and 20 ( E20), and from the first 21 days of postnatal development. Rhbg was expressed initially at E18, with expression only in the connecting tubule (CNT); at E20, Rhbg was expressed in both the CNT and the medullary collecting duct (MCD). In contrast, Rhcg was first expressed at E16 with basal expression in the ureteric bud; at E18, it was expressed in a subset of CNT cells with an apical pattern, followed by apical and basolateral expression in the MCD at E20. In the cortex, Rhbg and Rhcg expression increased in the CNT before expression in the cortical collecting duct during fetal development. In the MCD, both Rhbg and Rhcg expression was initially in cells in the papillary tip, with gradual removal from the tip during the late fetal period and transition during the early neonatal period to an adult pattern with predominant expression in the outer MCD and only rare expression in cells in the initial inner MCD. Double-labeling with intercalated cell-specific markers identified that Rhbg and Rhcg were expressed initially in CNT cells, CNT A-type intercalated cells and non-A, non-B intercalated cells, and in MCD A-type intercalated cells. We conclude that expression of Rhbg and Rhcg parallels intercalated cell development and that immature Rhbg and Rhcg expression at birth contributes to incomplete ammonia excretion capacity.
Circulating bioactive and immunoreactive IGF-I remain stable in women, despite physical fitness improvements after 8 weeks of resistance, aerobic, and combined exercise training
Authors: Nindl Bradley C. , Alemany Joseph A. , Tuckow Alexander P. , Rarick Kevin R. , Staab Jeffery S. , Kraemer William J. , Maresh Carl M. , Spiering Barry A. , Hatfield Disa L. , Flyvbjerg Allan , Frystyk Jan
Published: April 2010

Insulin-like growth factor-I (IGF-I) is regulated by a number of IGF-binding proteins (IGFBPs) and proteases that influence IGF-I bioactivity. A specific IGF-I kinase receptor activation assay (KIRA) has been developed that determines the ability of IGF-I to activate the IGF-I receptor by quantification of intracellular receptor autophosphorylation on IGF-I binding. KIRA-assessed IGF-I bioactivity has not been utilized within the context of chronic exercise training paradigms. This study measured total and free immunoreactive IGF-I, bioactive IGF-I, and IGFBP-1, -2, and -3 before (Pre), during (Mid), and after (Post) 8 wk of exercise training in young, healthy women, who were randomized into one of four groups: control ( n = 10), resistance ( n = 18), aerobic ( n = 13), and combined ( n = 15) exercise training. The training programs were effective in improving physical fitness specific to the exercise mode engaged in: increases were observed for lean mass (∼2%), aerobic fitness (6–7%), and upper (20–24%) and lower (15–48%) body strength (all P values < 0.05). By contrast, no time, group, or interaction effects were observed for the circulating IGF-I system, as immunoreactive total (Pre = 264 ± 16 μg/l; Mid = 268 ± 17 μg/l; Post = 271 ± 17 μg/l), free (Pre = 0.70 ± 0.1 μg/l; Mid = 0.63 ± 0.1 μg/l; Post = 0.63 ± 0.2 μg/l) and bioactive (Pre = 2.35 ± 0.3 μg/l; Mid = 2.25 ± 0.3 μg/l; Post = 2.33 ± 0.3 μg/l) IGF-I were unchanged throughout the study. All IGFBP measures were also unchanged. We conclude that increased lean mass, aerobic fitness, and upper and lower body strength resulting from an 8-wk exercise training programs can occur without concomitant increases in either circulating bioactive or immunoreactive IGF-I, as well as associated IGFBPs. In terms of reflecting positive anabolic neuromuscular outcomes, these data do not support a role for endocrine-derived IGF-I.
Spatial Arrangement of Glomerular Molecular-Feature Clusters in the Odorant-Receptor Class Domains of the Mouse Olfactory Bulb
Authors: Matsumoto Hideyuki , Kobayakawa Ko , Kobayakawa Reiko , Tashiro Takuya , Mori Kenji , Sakano Hitoshi , Mori Kensaku
Published: April 2010

The glomerular layer of the mammalian olfactory bulb (OB) forms odorant receptor (OR) maps. Each OR map is structurally and functionally compartmentalized into zones (dorsal and ventral) and domains (DI and DII in the dorsal zone). We previously reported that glomeruli with similar molecular receptive range properties formed molecular feature clusters at stereotypical positions in the rat OB. However, the spatial arrangement of the molecular feature clusters with regard to the OR zones and domains has not been systematically examined. In this study, we optically mapped the molecular feature clusters of glomeruli within the domain and zone framework of the OB using domain-visible class II GFP transgenic mice. In all mice examined, fatty acid-responsive cluster A was located in the lateral part of domain DI, whereas clusters B, C, and D were arranged in an anterior to posterior order within domain DII. We also found a new cluster of glomeruli that respond to fox odor trimethyl-thiazoline and its structural analogs (heterocyclic odorants that contain sulfur and nitrogen atoms within the ring). This cluster (named cluster J) was located posterior to cluster D within the DII domain. These results show that molecular feature clusters correspond to specific subsets of glomeruli in selective domains of the OR map, suggesting that the molecular feature clusters represent specific ORs that have similar molecular receptive range properties and functional roles.
Dissociable Neural Responses to Hands and Non-Hand Body Parts in Human Left Extrastriate Visual Cortex
Authors: Bracci Stefania , Ietswaart Magdalena , Peelen Marius V. , Cavina-Pratesi Cristiana
Published: April 2010

Accumulating evidence points to a map of visual regions encoding specific categories of objects. For example, a region in the human extrastriate visual cortex, the extrastriate body area (EBA), has been implicated in the visual processing of bodies and body parts. Although in the monkey, neurons selective for hands have been reported, in humans it is unclear whether areas selective for individual body parts such as the hand exist. Here, we conducted two functional MRI experiments to test for hand-preferring responses in the human extrastriate visual cortex. We found evidence for a hand-preferring region in left lateral occipitotemporal cortex in all 14 participants. This region, located in the lateral occipital sulcus, partially overlapped with left EBA, but could be functionally and anatomically dissociated from it. In experiment 2, we further investigated the functional profile of hand- and body-preferring regions by measuring responses to hands, fingers, feet, assorted body parts (arms, legs, torsos), and non-biological handlike stimuli such as robotic hands. The hand-preferring region responded most strongly to hands, followed by robotic hands, fingers, and feet, whereas its response to assorted body parts did not significantly differ from baseline. By contrast, EBA responded most strongly to body parts, followed by hands and feet, and did not significantly respond to robotic hands or fingers. Together, these results provide evidence for a representation of the hand in extrastriate visual cortex that is distinct from the representation of other body parts.
The Slack Sodium-Activated Potassium Channel Provides a Major Outward Current in Olfactory Neurons of Kv1.3−/− Super-Smeller Mice
Authors: Lu Songqing , Das Paromita , Fadool Debra A. , Kaczmarek Leonard K.
Published: April 2010

The Kv1.3 voltage-dependent potassium channel is expressed at high levels in mitral cells of the olfactory bulb (OB). Deletion of the Kv1.3 potassium channel gene (Kv1.3−/−) in mice lowers the threshold for detection of odors, increases the ability to discriminate between odors, and alters the firing pattern of mitral cells. We have now found that loss of Kv1.3 produces a compensatory increase in Na+-activated K+ currents (KNa) in mitral cells. Levels of the KNa channel subunit Slack-B determined by Western blotting are substantially increased in the OB from Kv1.3−/− animals compared with those of wildtype animals. In voltage-clamp recordings of OB slices, elevation of intracellular sodium from 0 to 60 mM increased mean outward currents by 15% in mitral cells from wildtype animals and by 40% in cells from Kv1.3−/− animals. In Kv1.3−/− cells, KNa current could even be detected with 0 mM Na+ internal solutions, provided extracellular Na+ was present, and this current could be abolished by TTX and ZD7288, blockers of Na+ influx through voltage-dependent Na+ channels and H-channels, respectively. The role of enhanced expression of Slack subunits in the increase of KNa current in Kv1.3−/− cells was also confirmed using an RNA interference (RNAi) approach to suppress Slack expression in primary cultures of olfactory neurons. In Kv1.3−/− neurons, treatment with Slack-specific RNAi inhibited approximately 75% of the net outward current, whereas in wildtype cells, the same treatment suppressed only about 25% of the total current. Scrambled and mismatched RNAi oligonucleotides failed to suppress currents. Our findings raise the possibility that the olfactory phenotype of Kv1.3−/− animals results in part from an enhancement of KNa currents.