bluuebunny/crossref_metadata_2025 huggingface dataset:
Dormancy and flowering in two mariposa lilies (Calochortus) with contrasting distribution patterns
Authors: Miller Michael T , Allen Geraldine A , Antos Joseph A
Published: January 2005

We investigated patterns of dormancy and reproduction over time in two long-lived grassland perennial species, Calochortus lyallii Baker and Calochortus macrocarpus Dougl. Three populations of each species were monitored over 5 years near Osoyoos, British Columbia, at the northern range limit for C. lyallii and near the elevational limit for C. macrocarpus. On average, C. macrocarpus bulbs flowered less frequently but had higher fruit set and produced more seeds per capsule than C. lyallii bulbs. In C. lyallii, low fruit set was related primarily to premature abortion of buds and flowers, whereas the potentially higher seed production of C. macrocarpus was largely offset by deer herbivory. Prolonged bulb dormancy was common in both species, with up to 18% of C. lyallii and 26% of C. macro carpus bulbs dormant in a given population and year. Dormancy episodes typically lasted a single year, although episodes as long as 4 years were also recorded. In both species dormancy was synchronized across sites, implying that it was not a random occurrence within populations but a response to the same external factor(s). Population surveys involving geophytes should consider the possibility that the visible population is not necessarily indicative of actual population size, and that a population may still be extant even when no individuals are observed.Key words: Calochortus, bulb dormancy, herbivory, range limits, geophyte, population persistence.
The problematic fossilTriplicatellafrom the Early Cambrian of Greenland, Canada, and Siberia
Authors: Skovsted Christian B , Peel John S , Atkins Christian J
Published: January 2005

The cap-shaped Early Cambrian fossil Triplicatella, previously known only from Australia, is reported from the upper Lower Cambrian of North and North-East Greenland, western Newfoundland, and Siberia. The occurrence of Triplicatella in Laurentia strengthens faunal ties between Laurentia and the Australian margin of Gondwana in late Early Cambrian times and supports hypotheses advocating the close proximity for the two palaeocontinents. Two new species, Triplicatella sinuosa n. sp., and T. peltata n. sp. are described, morphological details of which help elucidate the functional morphology and taxonomic affinity of the group. Three opercular types attributable to Triplicatella are left in open taxonomy. The postulated affinity of Triplicatella to hyoliths is confirmed, although the genus can not be placed within either of the two orders of hyoliths currently recognized.
The Holland Paleosol: an informal pedostratigraphic unit in the coastal dunes of southeastern Lake Michigan
Authors: Arbogast Alan F , Schaetzl Randall J , Hupy Joseph P , Hansen Edward C
Published: January 2005

A very prominent buried soil crops out in coastal sand dunes along an ~200 km section of the southeastern shore of Lake Michigan. This study is the first to investigate the character of this soil  informally described here as the Holland Paleosol  by focusing on six sites from Indiana Dunes National Lakeshore north to Montague, Michigan. Most dunes in this region are large (>40 m high) and contain numerous buried soils that indicate periods of reduced sand supply and comcomitant stabilization. Most of these soils are buried in the lower part of the dunes and are thin Entisols. The soil described here, in contrast, is relatively well developed, is buried in the upper part of many dunes, and formed by podzolization under forest vegetation. Radiocarbon dates indicate that this soil formed between ~3000 and 300 calibrated years BP. Pedons of the Holland Paleosol range in development from thick Entisols (Regosols) with ABwBCC horizonation to weakly developed Spodosols (Podzols) with AEBsBwBCC profiles. Many profiles have overthickened and (or) stratified A horizons, indicative of slow and episodic burial. Differences in development are mainly due to paleolandscape position and variations in paleoclimate among the sites. The Holland Paleosol is significant because it represents a relatively long period of landscape stability in coastal dunes over a broad (200 km) area. This period of stability was concurrent with numerous fluctuations in Lake Michigan. Given the general sensitivity of coastal dunes to prehistoric lake-level fluctuations, the soil may reflect a time when the lake shore was farther west than it is today. The Holland Paleosol would probably qualify as a formal pedostratigraphic unit if it were buried by a formal lithostratgraphic or allostratigraphic unit.
High-resolution stratigraphy of the deep-water lower Cloridorme Formation (Ordovician), Gaspé Peninsula, based on K-bentonite and megaturbidite correlations
Authors: Awadallah Sherif AM , Hiscott Richard N
Published: January 2005

The Ordovician Cloridorme Formation is a thick foreland-basin turbidite succession that for several decades has served as a natural laboratory for the long-distance physical tracing and study of single turbidites. A robust temporal correlation of these deposits is a prerequisite for the evaluation of sedimentary processes. Published stratigraphic subdivisions of the lower part of the Cloridorme Formation have impeded rather than facilitated such studies because of errors in the physical correlation of contemporaneous deposits. Tracing of the deposits of exceptionally large gravity flows, known as "megaturbidites," was previously recognized as a useful stratigraphic tool. Here, we strengthen and revise the stratigraphic framework based on megaturbidites by considering nine widely traceable and geochemically fingerprinted tuffs (K-bentonites). Two discriminant functions incorporating the abundances of six trace elements (V, Sm, Nd, Th, Er, Zr) permit the unambiguous distinction of the lower four tuffs. The other tuffs can be successfully distinguished using bivariate plots of TiO2, Th, Sc, and Eu. The tracing and correlation of 71 megaturbidites and the nine K-bentonites permits a high-resolution subdivision of the lower Cloridorme Formation. Particularly thick megaturbidites mark the boundaries of three newly defined allostratigraphic members (St-Hélier Allomember, St-Yvon Allomember, and Petite-Vallée Allomember). This precise temporal framework shows that the stratigraphic heights of the contacts of lithostratigraphic members defined by other workers in 1969 and 1991 were miscorrelated by more than 400 m over short lateral distances!
Early Carboniferous deformation and mineralization in the Cobequid shear zone, Nova Scotia: an 40Ar/39Ar geochronology study
Authors: Pe-Piper Georgia , Reynolds Peter H , Nearing Joe , Piper David JW
Published: January 2005

Latest Devonian to Early Carboniferous igneous rocks along the Cobequid shear zone of central Nova Scotia record a complex history of intrusion, volcanism, deformation, and hydrothermal alteration. Twenty new 40Ar/39Ar age determinations have been made on biotite and hornblende separates from rocks that constrain these events. The mafic plutons of the Cobequid shear zone are synchronous with the previously dated granitoid plutons (363355 ± 4 Ma), with the exception of the younger Folly Lake gabbro (355350 ± 4 Ma). High temperature shear deformation continued along the Cobequid shear zone during this entire period of pluton emplacement. Several samples from mylonitic and hydrothermally altered rocks with dates ca. 340 Ma indicate renewed movement along the Cobequid shear zone at this time, accompanied by minor magmatism. Younger ∼330320 Ma ages reflect final movement along the Rockland Brook fault resulting in mid-Namurian uplift of the Cobequid Highlands. Following this regional Alleghenian event, there was no significant motion on the northern faults of the Cobequid shear zone and deformation moved southward to the Cobequid fault and its continuation in the Hollow and Chedabucto fault zones. Hydrothermal alteration, probably driven by a mid-crustal gabbro heat source, was widespread along the Cobequid and Rockland Brook faults in the early Carboniferous, resulting in albitization, potassic alteration, and iron mineralization.
The tephra stratigraphy of two lakes in south-central British Columbia, Canada and its implications for mid-late Holocene volcanic activity at Glacier Peak and Mount St. Helens, Washington, USA
Authors: Foit Jr. Franklin F , Gavin Daniel G , Hu Feng Sheng
Published: January 2005

Several mid-late Holocene Glacier Peak tephras along with Mazama and Mount St. Helens Wn and P tephras were found in cores from Cooley and Rockslide lakes in southeastern British Columbia, ∼300 km northeast of Glacier Peak. The sediments in Cooley Lake host the late Holocene Glacier Peak A tephra (2010 calibrated (cal) years BP), four separate Glacier Peak Dusty Creek (GPDC) tephras (57805830 cal years BP), and a Glacier Peak set D tephra (6060 cal years BP). This is the first report of Glacier Peak A and D tephras in British Columbia. The A tephra has been correlated on the basis of glass composition and age to a late Holocene Glacier Peak tephra in the sediments of Big Twin Lake, 75 km northeast of Glacier Peak. The glasses in the four GPDC tephra layers from Cooley Lake are compositionally indistinguishable from those in Mount Barr Cirque and Frozen lakes in southwestern British Columbia. The layers likely represent four eruptions taking place over 50 years. Although set D tephra has not been correlated to a known proximal or distal deposit, its glass bears the Glacier Peak glass compositional signature and its interpolated age corresponds to the initiation of the set D eruptive period. The presence of GPDC tephra in lake sediments across southern British Columbia suggests a broad plume trajectory to the north and northeast, whereas the apparent absence of the A and D tephras in all but Cooley Lake suggest plumes with a northeasterly direction.
MazatzalLabradorian-age (1.71.6 Ga) ductile deformation of the South Range Sudbury impact structure at the Thayer Lindsley mine, Ontario
Authors: Bailey J , Lafrance B , McDonald A M , Fedorowich J S , Kamo S , Archibald D A
Published: January 2005

The Thayer Lindsley mine is located in the South Range of the Sudbury impact structure, near the contact between the 1.85 Ga Sudbury Igneous Complex (SIC) and the Paleoproterozoic Southern Province. NiCu ore zones at the mine are strongly deformed within a southeast-dipping, lower amphibolite-grade shear zone, which offsets the contact between the SIC and Southern Province rocks. Numerous shear sense indicators, including shear bands, drag folds, and δ- and σ-type rotated porphyroclasts, consistently indicate south-over-north, reverse, dip-slip movement parallel to the mineral stretching lineation in the shear zone. The attitude, slip direction, and metamorphic grade of the shear zone are similar to those of the regional northeast-striking South Range Shear Zone that formed during post-impact, northwest-directed ductile contraction of the Sudbury impact structure. The South Range Shear Zone is generally interpreted as a ca. 1.91.8 Ga Penokean structure. Anhedral brown titanite grains from the Thayer Lindsley shear zone yield a mean 207Pb/206Pb Penokean age of 1815 ± 15 Ma. These grains are mantled by younger, syntectonic, colourless titanite, which have a mean 207Pb/206Pb age of 1658 ± 68 Ma. This younger age suggests that the South Range and Thayer Lindsley shear zones may have formed during a 1.71.6 Ga collisional tectonic event that is recorded along the southeast margin of Laurentia from the southwest USA. (Mazatzal Orogeny), through the mid-continent to Wisconsin, and as far northeast as Labrador (Labradorian Orogeny). 40Ar/39Ar analyses indicate post-tectonic thermal resetting of biotite occurred at 1477 ± 8 Ma during felsic plutonism across the Sudbury area.
Exo selectivity and the effect of disubstitution in the DielsAlder reactions of butadiene with 3,3-disubstituted cyclopropenes
Authors: Gosse Tammy L , Poirier Raymond A
Published: January 2005

A density functional computational study was performed to accomplish two tasks: to examine the endoexo selectivity in the DielsAlder reactions of 3,3-disubstituted cyclopropenes with s-cis-butadiene, and to study the effect of disubstitution on the reactivity of the cyclopropene dienophile. Cyclopropene is substituted at C-3 with CH3, SiH3, NH2, PH2, OH, SH, F, and Cl; both 3-substituted and 3,3-disubstituted ground states are examined to determine relative reactivities. The exo transition-state structures are consistently lower in energy than the endo transition-state structures for the 3,3-disubstituted cyclopropene  butadiene system, and surprisingly, both modes of addition have lower activation barriers than the syn 3-substituted cyclopropene  butadiene system. Through a series of isodesmic reactions, we have concluded that there is an additional stabilization in the transition-state structures of the 3,3-disubstituted system that can account for the lowering of the activation barriers below that of the 3-substituted cases. This stabilization is a combination of the anomeric effect and the ring relaxation that occurs in the transition-state structure.Key words: DielsAlder reaction, cyclopropene, exo selectivity, anomeric effect.
Lithiation of 1-arylimidazol-2(1H)-ones and 1-aryl-4,5-dihydroimidazol-2(1H)-ones
Authors: Llopart Carme Cantos , Ferrer Conchita , Joule John A
Published: January 2005

1-Arylimidazol-2(1H)-ones are shown to be readily lithiated, using 2 mol equiv. of n-butyllithium, on the benzene ring, ortho to the heterocycle. 1-Aryl-4,5-dihydroimidazol-2(1H)-ones also undergo metalation on the aromatic substitutuent ortho to the heterocycle, but less efficiently. 1-Aryl-3-methylimidazol-2(1H)-ones are lithiated on the heterocyclic ring and then on the benzene ring ortho to the heterocycle. No ortho-directing effect was found for 1-aryl-4,5-dihydro-3-methylimidazol-2(1H)-ones.Key words: ortho-lithation, ureas for directed ortho metalation, 1-arylimidazol-2-ones, 1-arylimidazolidin-2-ones.
Early dietary intervention: long-term effects on blood pressure, brain neuropeptide Y, and adiposity markers
Authors: Velkoska Elena , Cole Timothy J. , Morris Margaret J.
Published: January 2005

Early life nutrition impacts on subsequent risk of obesity and hypertension. Several brain chemicals responsible for both feeding and cardiovascular regulation are altered in obesity. We examined effects of early postnatal overnutrition on blood pressure, brain neuropeptide Y (NPY), and adiposity markers. Rat pup litters were adjusted to either 3 or 12 male animals (overnutrition and control, respectively) on day 1 of life. After weaning, rats were given either a palatable high-fat diet or standard chow. Smaller litter pups were significantly heavier by 17 days of age. By 16 wk, the effect of litter size was masked by that of diet, postweaning. Small and normal litter animals fed a high-fat diet had similar increases in body weight, plasma insulin, leptin, and adiponectin concentrations, leptin mRNA, and fat masses relative to chow-fed animals. An increase in 11β-hydroxysteroid dehydrogenase-1 mRNA in white adipose tissue, and a decrease in uncoupling protein-1 mRNA in brown adipose tissue in both small litter groups at 16 wk of age, may represent a programming effect of the altered litter size. NPY concentration in the paraventricular nucleus of the hypothalamus was reduced in high fat-fed groups. Blood pressure was significantly elevated at 13 wk in high-fat-fed animals. This study demonstrates that overnourishment during early postnatal development leads to profound changes in body weight at weaning, which tended to abate with maturation. Thus the effects of long-term dietary intervention postweaning can override those of litter size-induced obesity.
PPARγ2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes
Authors: Schadinger Susan E. , Bucher Nancy L. R. , Schreiber Barbara M. , Farmer Stephen R.
Published: January 2005

Peroxisome proliferator-activated receptor-γ (PPARγ) is considered to be one of the master regulators of adipocyte differentiation. PPARγ2 is abundantly expressed in mature adipocytes and is elevated in the livers of animals that develop fatty livers. The aim of this study was to determine the ability of PPARγ2 to induce lipid accumulation in hepatocytes and to delineate molecular mechanisms driving this process. The hepatic cell line AML-12 was used to generate a cell line stably expressing PPARγ2. Oil Red O staining revealed that PPARγ2 induces lipid accumulation in hepatocytes. This phenotype is accompanied by a selective upregulation of several adipogenic and lipogenic genes including adipose differentiation-related protein (ADRP), adipocyte fatty acid-binding protein 4, sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase, genes whose expression levels are known to increase in steatotic livers of ob/ob mice. Furthermore, the PPARγ2-regulated induction of both SREBP-1 and FAS parallels an increase in de novo triacylglycerol synthesis in hepatocytes. Triacylglycerol synthesis and lipid accumulation are further enhanced by culturing hepatocytes with troglitazone in the absence of exogenous lipids. These results correspond with an increase in the lipid droplet protein, ADRP, and the data demonstrate that ADRP functions to coat lipid droplets in hepatocytes as observed by confocal microscopy. Taken together, these observations propose a role for PPARγ2 as an inducer of steatosis in hepatocytes and suggest that this phenomenon occurs through an induction of pathways regulating de novo lipid synthesis.
Anabolic effects of insulin and IGF-I in the ovine fetus are reduced by prolonged maternal fasting
Authors: Shen Weihua , Wisniowski Paul , Denne Scott C. , Boyle David W. , Liechty Edward A.
Published: January 2005

Fetal nutritional stress may result in intrauterine growth restriction and postnatal insulin resistance. To determine whether insulin resistance can begin in utero, we subjected late-gestation (130–135 days) ewes to 120 h of complete fasting and compared the results with our previous work in fed ewes ( 38 ). We determined the effect of insulin and/or recombinant human (rh)IGF-I infusion on ovine fetal phenylalanine kinetics, protein synthesis, and phenylalanine accretion. Experimental infusates were 1) saline, 2) rhIGF-I plus a replacement dose of insulin (40 nmol IGF-I/h + 16 mIU insulin/h), 3) insulin (890 mIU/h), and 4) IGF-I plus insulin (40 nmol IGF-I/h + 890 mIU insulin/h). During hormone infusion, both glucose and amino acid concentrations were clamped at basal concentrations. Amino acid infusion was required during infusion of either hormone to maintain plasma concentrations constant. However, the amount required during insulin infusion was less than during IGF-I infusion and 40% less than the amount required during identical studies in nonfasted animals. Phenylalanine used for protein synthesis and accretion was increased compared with control animals but again less so than in the nonfasted animals. In contrast to nonfasted animals, neither hormone increased the fractional synthetic rate of skeletal muscle protein nor that of plasma albumin. These results indicate that a short but severe nutritional stress can significantly alter the fetal anabolic response to insulin even when both glucose and amino acid substrate supplies are restored. Therefore, adaptive responses characterized by insulin resistance begin in utero when the fetus is subjected to sufficient nutritional stress.
Endotoxemic acute renal failure is attenuated in caspase-1-deficient mice
Authors: Wang Wei , Faubel Sarah , Ljubanovic Danica , Mitra Amit , Falk Sandor A. , Kim Jun , Tao Yunxia , Soloviev Andrei , Reznikov Leonid L. , Dinarello Charles A. , Schrier Robert W. , Edelstein Charles L.
Published: January 2005

Caspase-1-deficient (−/−) mice are protected against sepsis-induced hypotension and mortality. We investigated the role of caspase-1 and its associated cytokines in a nonhypotensive model of endotoxemic acute renal failure (ARF). Mice were injected intraperitoneally with 2.5 mg of LPS that induces endotoxemic ARF. On immunoblot analysis of whole kidney, there was an increase in caspase-1 protein in LPS-treated mice compared with vehicle-treated controls. In LPS-treated mice, the glomerular filtration rate (GFR) was significantly higher in caspase-1 −/− vs. wild-type mice at 16 and 36 h after LPS. To determine the mechanism of this protection, the caspase-1-activated cytokines IL-1β and IL-18 were investigated. IL-1β and IL-18 protein were significantly increased in the kidneys of LPS- vs. vehicle-treated mice. To determine the role of these cytokines, mice were treated with recombinant IL-1 receptor antagonist (IL-1Ra) or IL-18-neutralizing antiserum. In LPS-treated mice, GFR was not different in IL-1Ra-treated or IL-18-neutralizing antiserum-treated or combination therapy (IL-1Ra plus IL-18-neutralizing antiserum-treated) compared with control mice. In addition, tubular cell apoptosis, neutrophil infiltration, myeloperoxidase activity, caspase-3 activity, and calpain activity were not different between wild-type and caspase-1 −/− mice with endotoxemic ARF. In LPS- vs. vehicle-treated wild-type mice, renal IL-1α was significantly increased. In both LPS- and vehicle-treated caspase-1 −/− mice, renal IL-1α was very low. In summary, caspase-1 −/− mice are functionally protected against endotoxemic ARF. Neutralization of IL-1β and IL-18 is not functionally protective. The role of the intracellular proinflammatory cytokine IL-1α in endotoxemic ARF merits further study.
Stimulation of AQP2 membrane insertion in renal epithelial cells in vitro and in vivo by the cGMP phosphodiesterase inhibitor sildenafil citrate (Viagra)
Authors: Bouley Richard , Pastor-Soler Nuria , Cohen Ori , McLaughlin Margaret , Breton Sylvie , Brown Dennis
Published: January 2005

Vasopressin-stimulated insertion of the aquaporin 2 (AQP2) water channel into the plasma membrane of kidney collecting duct principal cells is a key event in the urinary concentrating mechanism. The paradigm for vasopressin-receptor signaling involves cAMP-mediated protein kinase A activation, which results in the functionally critical phosphorylation of AQP2 on amino acid serine 256. We previously showed that a parallel cGMP-mediated signaling pathway also leads to AQP2 membrane insertion in AQP2-transfected LLC-PK1(LLC-AQP2) cells and in outer medullary collecting duct principal cells in situ (Bouley R, Breton S, Sun T, McLaughlin M, Nsumu NN, Lin HY, Ausiello DA, and Brown D. J Clin Invest 106: 1115–1126, 2000). In the present report, we show by immunofluorescence microscopy, and Western blotting of plasma membrane fractions, that 45-min exposure of LLC-AQP2 cells to the cGMP phosphodiesterase type 5 (PDE5) inhibitors sildenafil citrate (Viagra) or 4-{[3',4'-methylene-dioxybenzyl]amino}-6-methoxyquinazoline elevates intracellular cGMP levels and results in the plasma membrane accumulation of AQP2; i.e., they mimic the vasopressin effect. Importantly, our data also show that acute exposure to PDE5 inhibitors for 60 min induces apical accumulation of AQP2 in kidney medullary collecting duct principal cells both in tissue slices incubated in vitro as well as in vivo after intravenous injection of Viagra into rats. These data suggest that AQP2 membrane insertion can be induced independently of vasopressin-receptor activation by activating a parallel cGMP-mediated signal transduction pathway with cGMP PDE inhibitors. These results provide proof-of-principle that pharmacological activation of vasopressin-independent, cGMP signaling pathways could aid in the treatment of those forms of nephrogenic diabetes insipidus that are due to vasopressin-2 receptor dysfunction.
Acetylcholine-induced vasodilation is mediated by nitric oxide and prostaglandins in human skin
Authors: Kellogg D. L. , Zhao J. L. , Coey U. , Green J. V.
Published: January 2005

Acetylcholine (ACh) can effect vasodilation by several mechanisms, including activation of endothelial nitric oxide (NO) synthase and prostaglandin (PG) production. In human skin, exogenous ACh increases both skin blood flow (SkBF) and bioavailable NO levels, but the relative increase is much greater in SkBF than NO. This led us to speculate ACh may dilate cutaneous blood vessels through PGs, as well as NO. To test this hypothesis, we performed a study in 11 healthy people. We measured SkBF by laser-Doppler flowmetry (LDF) at four skin sites instrumented for intradermal microdialysis. One site was treated with ketorolac (Keto), a nonselective cyclooxygenase antagonist. A second site was treated with NG-nitro-l-arginine methyl ester (l-NAME) to inhibit NO synthase. A third site was treated with a combination of Keto and l-NAME. The fourth site was an untreated control site. After the three treated sites received the different inhibiting agents, ACh was administered to all four sites by intradermal microdialysis. Finally, sodium nitroprusside (SNP) was administered to all four sites. Mean arterial pressure (MAP) was monitored by Finapres, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP). For data analysis, CVC values for each site were normalized to their respective maxima as effected by SNP. The results showed that both Keto and l-NAME each attenuated the vasodilation induced by exogenous ACh (ACh control = 79 ± 4% maximal CVC, Keto = 55 ± 7% maximal CVC, l-NAME = 46 ± 6% maximal CVC; P < 0.05, ACh vs. Keto or l-NAME). The combination of the two agents produced an even greater attenuation of ACh-induced vasodilation (31 ± 5% maximal CVC; P < 0.05 vs. all other sites). We conclude that a portion of the vasodilation effected by exogenous ACh in skin is due to NO; however, a significant portion is also mediated by PGs.
Postexercise hypotension is not explained by a prostaglandin-dependent peripheral vasodilation
Authors: Lockwood Jennifer M. , Pricher Mollie P. , Wilkins Brad W. , Holowatz Lacy A. , Halliwill John R.
Published: January 2005

In normally active individuals, postexercise hypotension after a single bout of aerobic exercise occurs due to an unexplained peripheral vasodilation. Prostaglandin production has been suggested to contribute to the increases in blood flow during and after exercise; however, its potential contribution to postexercise hypotension has not been assessed. The purpose of this study was to determine the potential contribution of a prostaglandin-dependent vasodilation to changes in systemic vascular conductance underlying postexercise hypotension; this was done by inhibiting production of prostaglandins with the cyclooxygenase inhibitor ibuprofen. We studied 11 healthy normotensive men (aged 23.7 ± 4.2 yr) before and during the 90 min after a 60-min bout of cycling at 60% peak O2 uptake on a control and a cyclooxygenase inhibition day (randomized). Subjects received 10 mg/kg of oral ibuprofen on the cyclooxygenase inhibition day. On both study days, arterial blood pressure (automated auscultation) and cardiac output (acetylene uptake) were measured, and systemic vascular conductance was calculated. Inhibition of cyclooxygenase had no effect on baseline values of mean arterial pressure or systemic vascular conductance ( P > 0.2). After exercise on both days, mean arterial pressure was reduced (−2.2 ± 1.0 mmHg change with the control condition and −3.8 ± 1.5 mmHg change with the ibuprofen condition, both P < 0.05 vs. preexercise) and systemic vascular conductance was increased (5.2 ± 5.0% change with the control condition and 8.7 ± 4.1% change with the ibuprofen condition, both P < 0.05 vs. preexercise). There were no differences between study days ( P > 0.6). These data suggest that prostaglandin-dependent vasodilation does not contribute to the increased systemic vascular conductance underlying postexercise hypotension.
Diminished overload-induced hypertrophy in aged fast-twitch skeletal muscle is associated with AMPK hyperphosphorylation
Authors: Thomson David M. , Gordon Scott E.
Published: January 2005

Skeletal muscle mass declines with age, as does the potential for overload-induced fast-twitch skeletal muscle hypertrophy. Because 5′-AMP-activated protein kinase (AMPK) activity is thought to inhibit skeletal muscle protein synthesis and may therefore modulate muscle mass and hypertrophy, the purpose of this investigation was to examine AMPK phosphorylation status (a marker of AMPK activity) and its potential association with the attenuated overload-induced hypertrophy observed in aged skeletal muscle. One-week overload of fast-twitch plantaris and slow-twitch soleus muscles was achieved in young adult (8 mo; n = 7) and old (30 mo; n = 7) Fischer344 × Brown Norway male rats via unilateral gastrocnemius ablation. Significant ( P ≤ 0.05) age-related atrophy (as measured by total protein content) was noted in plantaris and soleus control (sham-operated) muscles. In fast-twitch plantaris muscles, percent hypertrophy with overload was significantly attenuated with age, whereas AMPK phosphorylation status as determined by Western blotting [phospho-AMPK (Thr172)/total AMPK] was significantly elevated with age (regardless of loading status). There was also a main effect of loading on AMPK phosphorylation status in plantaris muscles (overload > control). Moreover, a strong and significant negative correlation ( r = −0.82) was observed between AMPK phosphorylation status and percent hypertrophy in the overloaded plantaris muscles of all animals. In contrast to the plantaris, overload-induced hypertrophy of the slow-twitch soleus muscle was similar between ages, and AMPK phosphorylation in this muscle was also unaffected by age or overload. These data support the possibility that an age-related elevation in AMPK phosphorylation may partly contribute to the attenuated hypertrophic response observed with age in overloaded fast-twitch plantaris muscle.
NOS3 deficiency augments hypoxic pulmonary vasoconstriction and enhances systemic oxygenation during one-lung ventilation in mice
Authors: Liu Rong , Evgenov Oleg V. , Ichinose Fumito
Published: January 2005

Nitric oxide (NO), synthesized by NO synthases (NOS), plays a pivotal role in regulation of pulmonary vascular tone. To examine the role of endothelial NOS (NOS3) in hypoxic pulmonary vasoconstriction (HPV), we measured left lung pulmonary vascular resistance (LPVR), intrapulmonary shunting, and arterial Po2 (PaO2) before and during left mainstem bronchus occlusion (LMBO) in mice with and without a deletion of the gene encoding NOS3. The increase of LPVR induced by LMBO was greater in NOS3-deficient mice than in wild-type mice (151 ± 39% vs. 109 ± 36%, mean ± SD; P < 0.05). NOS3-deficient mice had a lower intrapulmonary shunt fraction than wild-type mice (17.1 ± 3.6% vs. 21.7 ± 2.4%, P < 0.05) during LMBO. Both real-time PaO2 monitoring with an intra-arterial probe and arterial blood-gas analysis during LMBO showed higher PaO2 in NOS3-deficient mice than in wild-type mice ( P < 0.05). Inhibition of all three NOS isoforms with Nω-nitro-l-arginine methyl ester (l-NAME) augmented the increase of LPVR induced by LMBO in wild-type mice (183 ± 67% in l-NAME treated vs. 109 ± 36% in saline treated, P < 0.01) but not in NOS3-deficient mice. Similarly, systemic oxygenation during one-lung ventilation was augmented by l-NAME in wild-type mice but not in NOS3-deficient mice. These findings indicate that NO derived from NOS3 modulates HPV in vivo and that inhibition of NOS3 improves systemic oxygenation during acute unilateral lung hypoxia.
Mid-Lumbar Segments Are Needed for the Expression of Locomotion in Chronic Spinal Cats
Authors: Langlet C. , Leblond H. , Rossignol S.
Published: January 2005

In acute experiments performed in decerebrated and spinalized (T13) cats, an intraspinal injection of clonidine, a noradrenergic agonist, restricted to mid-lumbar segments L3–L4, can induce hindlimb locomotion, whereas yohimbine, a noradrenergic antagonist, can block spinal locomotion, and a second spinal lesion at L4 can abolish all locomotor activity. In the present study, we investigated whether the abolition of locomotion after this second spinal lesion was due to an acute spinal shock or to the functional disconnection of the rostral and caudal lumbar segments. In seven cats, first spinalized at T13 and having recovered treadmill locomotion, a second transection was performed at lower lumbar levels. Video and electromyographic recordings were used to evaluate locomotor performance. Results show that after a second transection at L2 or rostral L3 levels, spinal locomotion was maintained; when the second lesion was performed at caudal L3 or L4, all locomotor activity was abolished even after several weeks of attempted locomotor training; vigorous fast paw shakes (FPS) were observed in all cases; and after an intraperitoneal injection of clonidine in cats with a second transection below L4, perineal stimulation induced hyperextension of the hindlimbs but no locomotion. Considering that the main motoneuron pools of the hindlimbs are caudal to L4 and are still functional after the second spinal transection, as evidenced by the presence of FPS, we conclude that the mid-lumbar spinal segments are essential for the specific expression of spinal locomotion but not necessarily for other rhythmic motor patterns.
Muscle Activity Determined by Cosine Tuning With a Nontrivial Preferred Direction During Isometric Force Exertion by Lower Limb
Authors: Nozaki Daichi , Nakazawa Kimitaka , Akai Masami
Published: January 2005

We investigated how the CNS selects a unique muscle activation pattern under a redundant situation resulting from the existence of bi-articular muscles. Surface electromyographic (EMG) activity was recorded from eight lower limb muscles while 11 subjects were exerting isometric knee and hip joint torque simultaneously ( Tk and Th, respectively. Extension torque was defined as positive). The knee joint was kept at either 90 or 60°. Various combinations of torque were imposed on both joints by pulling a cable attached to an ankle brace with approximately three levels of isometric force in 16 directions. The distribution of the data in the three-dimensional plot (muscle activation level quantified by the root mean squared value of EMG vs. Tk and Th) demonstrates that the muscle activation level M can be approximated by a single model as M = ⌊ aTk + bTh⌋ where ⌊ x⌋ = max ( x,0) and a and b are constants. The percentage of variance explained by this model averaged over all muscles was 82.3 ± 14.0% (mean ± SD), indicating that the degree of fit of the data to the plane was high. This model suggests that the CNS uses a cosine tuning function on the torque plane ( Tk, Th) to recruit muscles. Interestingly, the muscle's preferred direction (PD) defined as the direction where it is maximally active on the torque plane deviated from its own mechanical pulling direction (MD). This deviation was apparent in the mono-articular knee extensor (MD = 0°, whereas PD = 14.1 ± 3.7° for vastus lateralis) and in the mono-articular hip extensor (MD = 90°, whereas PD = 53.4 ± 6.4° for gluteus maximus). Such misalignment between MD and PD indicates that the mono-articular muscle's activation level depends on the torque of the joint that it does not span. Practical implications of this observation for the motor control studies were discussed. We also demonstrated that the observed shift from the MD to the PD is plausible in the configuration of our musculo-skeletal system and that the experimental results are likely to be explained by the CNS process to minimize the variability of the endpoint force vector under the existence of signal-dependent noise.
A-Type Voltage-Gated K+ Currents Influence Firing Properties of Isolectin B4-Positive But Not Isolectin B4-Negative Primary Sensory Neurons
Authors: Vydyanathan Amaresh , Wu Zi-Zhen , Chen Shao-Rui , Pan Hui-Lin
Published: January 2005

Voltage-gated K+ channels (Kv) in primary sensory neurons are important for regulation of neuronal excitability. The dorsal root ganglion (DRG) neurons are heterogeneous, and the types of native Kv currents in different groups of nociceptive DRG neurons are not fully known. In this study, we determined the difference in the A-type Kv current and its influence on the firing properties between isolectin B4 (IB4)-positive and -negative DRG neurons. Whole cell voltage- and current-clamp recordings were performed on acutely dissociated small DRG neurons of rats. The total Kv current density was significantly higher in IB4-positive than that in IB4-negative neurons. Also, 4-aminopyridine (4-AP) produced a significantly greater reduction in Kv currents in IB4-positive than in IB4-negative neurons. In contrast, IB4-negative neurons exhibited a larger proportion of tetraethylammonium-sensitive Kv currents. Furthermore, IB4-positive neurons showed a longer latency of firing and required a significantly larger amount of current injection to evoke action potentials. 4-AP significantly decreased the latency of firing and increased the firing frequency in IB4-positive but not in IB4-negative neurons. Additionally, IB4-positive neurons are immunoreactive to Kv1.4 but not to Kv1.1 and Kv1.2 subunits. Collectively, this study provides new information that 4-AP–sensitive A-type Kv currents are mainly present in IB4-positive DRG neurons and preferentially dampen the initiation of action potentials of this subpopulation of nociceptors. The difference in the density of A-type Kv currents contributes to the distinct electrophysiological properties of IB4-positive and -negative DRG neurons.
Posaconazole Pharmacokinetics, Safety, and Tolerability in Subjects With Varying Degrees of Chronic Renal Disease
Authors: Courtney R. , Sansone A. , Smith W. , Marbury T. , Statkevich P. , Martinho M. , Laughlin M. , Swan S.
Published: January 2005

Posaconazole is a triazole antifungal in development for the treatment of invasive fungal infections. The authors evaluated the pharmacokinetics and safety of posaconazole in healthy subjects and in those with mild (CLCR = 50–80 mL/min), moderate (CLCR = 20–49 mL/min), and severe chronic renal disease (CLCR <20 mL/min; receiving outpatient hemodialysis) (n = 6/group). Subjects received one 400‐mg dose of posaconazole oral suspension with a standardized high‐fat breakfast. For hemodialysis‐dependent subjects, this dose was given on a nonhemodialysis day, and a second 400‐mg dose was given 6 hours before hemodialysis. Blood samples were collected before dose and up to 120 hours postdose. For hemodialysis‐dependent subjects following the second dose, additional samples (predialyzed and postdialyzed) were collected before, during, and after dialysis. There was no correlation between posaconazole pharmacokinetics and mild to moderate renal disease; the slopes of the linear regressions for creatinine clearance versus posaconazole AUC, Cmax, CL/F, and t1/2 values were not significantly different from zero (P > .130). Mean CL/F values before and during hemodialysis were comparable. Furthermore, the difference in the predialyzed and postdialyzed posaconazole concentrations was only ∼3%, supporting that posaconazole was not removed by hemodialysis. Protein binding was similar in all groups (∼98%) and was unaffected by hemodialysis. Posaconazole was generally well tolerated. One patient had elevated liver function test results that were not present at baseline and were thought to be possibly related to posaconazole. Results of this single‐dose study indicate that dosage adjustments for patients with varying degrees of renal disease are not required.
Interaction of Warfarin With Drugs, Natural Substances, and Foods
Authors: Greenblatt David J. , von Moltke Lisa L.
Published: January 2005

Variability in the anticoagulant response to warfarin is an ongoing clinical dilemma. Fluctuations in dietary vitamin K are an important source of variance, and the need for constancy in vitamin K intake is routinely emphasized for warfarin‐treated patients. Anticoagulant response is also influenced by a number of drugs that induce or inhibit warfarin metabolism, as well as by genetic polymorphisms that may modulate expression or activity of CYP2C9, the isoform mediating clearance of S‐warfarin. The possible role of dietary factors other than vitamin K, as well as of herbal medicines or supplements as contributors to the instability of anticoagulation in warfarin‐treated patients, has received recent attention. St. John's wort and possibly some ginseng formulations may have the potential to diminish warfarin anticoagulation, apparently by inducing CYP2C9 activity. Otherwise, there is no reliable evidence to indicate that any dietary component (other than vitamin K) or any herbal product has an effect on the anticoagulant response to warfarin. Scientific conclusions on this important therapeutic issue should be based on valid scientific data rather than unvalidated case reports.
The Influence of Norfloxacin and Metronidazole on the Disposition of Mycophenolate Mofetil
Authors: Naderer Odin J. , Dupuis Robert E. , Heinzen Erin L. , Wiwattanawongsa Kamonthip , Johnson Mark W. , Smith Philip C.
Published: January 2005

The objective of this study was to investigate the effect of concurrent antibiotic administration on the disposition of mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG) after oral administration of mycophenolate mofetil (MMF) in healthy subjects. Eleven healthy subjects were enrolled. The study was divided into 4 treatment periods. Subjects received MMF as a single oral 1‐g dose alone and were then randomized to 3 antibiotic treatment periods. The 3 periods included norfloxacin, metronidazole, and a combination of norfloxacin and metronidazole. Antibiotic treatment was started 3 days prior to each MMF pharmacokinetic study day and was given for a total of 5 days. On day 4 of each antibiotic phase, subjects received a single 1‐g oral dose of MMF. Plasma and urine samples were obtained over 48 hours after the MMF dose in all treatment periods and were quantitatively measured for MPA and MPAG. Pharmacokinetic parameters for MPA and MPAG were determined for all periods. Compared to MMF alone, the area under the plasma concentration versus time curve (AUC) of MPA was reduced by an average of 10%, 19%, and 33% when given with norfloxacin, metronidazole, and norfloxacin plus metronidazole, respectively. The AUC of MPAG was also reduced on average by 10%, 27%, and 41% in the corresponding periods. The combination of norfloxacin and metronidazole significantly reduced the AUC of MPA and MPAG in healthy subjects. This likely occurs as a result of reduced enterohepatic recirculation.
Coping with Wage Regulation
Authors: Druker Janet , White Geoffrey , Stanworth Celia
Published: January 2005

This article investigates the effects of the introduction and uprating of the National Minimum Wage (NMW) on hairdressing businesses in the UK. The focus is on owner-manager responses to the NMW, in terms of business management, the utilization of human resources and whether the NMW constituted a ‘regulatory shock’. The data was collected from 48 in-depth interviews with hairdressing businesses in all regions of the UK during 2002. The research project was funded by the Low Pay Commission (LPC), and was designed to reflect the diversity of the hairdressing industry in terms of location, size of firm and type of services offered. The advent of the NMW did not act as a regulatory shock, and responses in terms of change to business management and utilization of staff can be best understood as reflections of existing philosophy and practice rather than a trigger for new directions.
Experience and Cognition
Authors: Westhead Paul , Ucbasaran Deniz , Wright Mike
Published: January 2005

Some policy makers and practitioners are considering whether resources could be more effectively utilized if they were targeted towards experienced entrepreneurs (i.e. individuals with prior private business ownership experience), rather than the provision of additional initiatives to increase the pool of inexperienced novice entrepreneurs. To inform this policy debate, similarities and differences between novice, serial and portfolio entrepreneurs are highlighted with regard to their experience and cognition. A stratified random sample of independent firms located throughout Scotland was identified. In total, 200 firms (56.5%) involved novice entrepreneurs. A further 66 firms involved serial entrepreneurs (18.6%). The remaining 88 firms involved portfolio entrepreneurs (24.9%). Portfolio entrepreneurs are associated with experience and cognitive mindsets that provide greater understanding surrounding why and how they own several businesses at the same time. A case for targeted support tailored to the aspirations and needs of novice, serial and portfolio entrepreneurs is presented.
Electronic Memory Aids for Community-Dwelling Elderly Persons: Attitudes, Preferences, and Potential Utilization
Authors: Cohen-Mansfield Jiska , Creedon Michael A. , Malone Thomas B. , Kirkpatrick Mark J. , Dutra Lisa A. , Herman Randy Perse
Published: January 2005

This article focuses on the attitudes of community-dwelling elderly persons toward the use of electronic memory aids. Questionnaire data from 100 elderly volunteers indicate that more than one half were interested in an electronic memory device for at least one purpose. Those who said that they would use the device had higher levels of education, used more household electronic devices, were more likely to have someone available to help them use a device, and had more health problems than those who preferred to not use it. Most would use a memory aid to monitor medications and remember appointments, followed by remembering addresses and phone numbers. The expected use, design, preferred methods of instruction, and concerns about the device varied. Study results suggest the need to develop devices with different degrees of flexibility and complexity. Future studies should evaluate training methods to use such technology.
HIV/AIDS and the Older Adult: An Exploratory Study of the Age-Related Differences in Access to Medical and Social Services
Authors: Fritsch Teresa
Published: January 2005

This exploratory study investigated the experiences that older adults infected with HIV/AIDS had accessing medical and social services, and compared their experiences to those of younger infected adults. Thirty-four individuals between ages 30 and 65 were interviewed, and data were analyzed quantitatively and qualitatively. The study found that overall, older adults aged 50-plus were able to access the medical and social services they needed to cope with being infected. Most study participants reported positive experiences with accessing medical services. Like younger adults, older adults accessed a variety of medical services and organizations, although to a slightly lesser degree. Older adults also accessed a variety of social and emotional supports and social organizations to a similar or greater degree than younger adults. The older adults’ positive and directive attitude, knowledge of the disease, and available supports, in addition to living in the gay community, explain their ability to access services.
Correlates of Five Intellectual Abilities in Chinese Older Adults
Authors: Chou Kee-Lee , Chi Iris
Published: January 2005

Whether older adults can maintain their independent living in community depends on their level of intellectual functioning. This study identified psychosocial factors contributing to five dimensions of intellectual abilities including verbal meaning, word fluency, spatial orientation, inductive reasoning, and number skill, which were measured by the Chinese version of the Primary Mental Abilities Scale. The respondents were 207 Hong Kong Chinese adults aged 60 years or older, and they were interviewed face to face. In hierarchical regression analyses, the authors found that the majority of variance of five intellectual abilities was accounted for by sociodemographic variables. Moreover, education was consistently associated with all five intellectual abilities, and the Lubben Social Network Scale was also significantly related to all five abilities except verbal meaning. Self-rated visual functioning was also related to respondents’ performance in three intellectual tests including word fluency, spatial orientation, and inductive reasoning.