bluuebunny/crossref_metadata_2025 huggingface dataset:
Wood density in Norway spruce: changes with thinning intensity and tree age
Authors: Jaakkola Tuula , Mäkinen Harri , Saranpää Pekka
Published: September 2005

The effect of thinning intensity on growth and wood density in Norway spruce (Picea abies (L.) Karst.) was investigated in two long-term thinning experiments in southeastern Finland. The stands were approaching maturity, and their development had already been studied for 30 years. The intensities of thinning were low, normal, and high (i.e., the stand basal area after the thinning was, on average, 40, 27, and 24 m2·ha1, respectively, in Heinola, and 30, 28, and 17 m2·ha1 in Punkaharju, respectively). Compared with the low thinning intensity, the normal and high thinning intensities increased the basal-area increment of individual trees by 52% and 68%, respectively. Normal and high thinning intensities resulted in a relatively small reduction (1%4%) of mean ring density compared with low thinning intensity. The random variation in wood density between and within trees was large. About 27% of the total variation in wood density was related to variation between rings. Our results indicate that the prevailing thinning intensities in Norway spruce stands in Fennoscandia cause no marked changes in wood density. At least, the possible reduction in wood density is low compared with the increase in individual tree growth.
On the role of enemies in divergence and diversification of prey: a review and synthesis
Authors: Vamosi Steven M
Published: September 2005

Understanding the contribution of ecological interactions to the origin and maintenance of diversity is a fundamental challenge for ecologists and evolutionary biologists, and one that is currently receiving a great deal of attention. Natural enemies (e.g., predators, parasites, and herbivores) are ubiquitous in food webs and are predicted to have significant impacts on phenotypic diversity and on speciation, and extinction rates of their prey. Spurred by the development of a theoretical framework beginning in the late 1970s, there is now a growing body of literature that addresses the effects of enemy–prey interactions on the evolution of prey. A number of theoretical models predict that enemies can produce phenotypic divergence between closely related species, even in the absence of interspecific competition for resources. Effects on diversification of prey are more variable, and enemies may either enhance or depress speciation and extinction rates of their prey. Empirical evidences from a number of study systems, notably those involving predators and prey in aquatic environments and interactions between insects and flowering plants, confirm both predictions. There is now considerable evidence for the role of enemies, especially those that are size-selective or use visual cues when identifying suitable prey, on phenotypic divergence of sympatric and allopatric taxa. Enemies may spur diversification rates in certain groups under some circumstances, and hinder diversification rates in other cases. I suggest that further research should focus on the role of enemies in diversification of prey, with significant insights likely to be the product of applying traditional experimental approaches and emerging comparative phylogenetic methods.
Female multiple mating for fertility assurance in red flour beetles (Tribolium castaneum)
Authors: Pai Aditi , Bennett Lauren , Yan Guiyun
Published: September 2005

The costs of mating with multiple partners include expenditure of energy and time and a reduction in lifespan, but females of many taxa mate with several different partners shortly after their first copulation. Often it is not clear what females gain from this behaviour. In this study, we used the red flour beetle (Tribolium castaneum Herbst, 1797) to test the hypothesis that females mate with multiple males for fertility assurance because the first copulation often does not lead to offspring production. We found that the probability of producing offspring, as measured by the proportion of females that produced offspring, was not affected by multiple mating when females were mated to virgin partners. However, when females were mated to nonvirgin partners, multiple mating led to an increased probability of producing offspring. To establish the mechanism through which multiple mating enhanced the probability of producing offspring, we further investigated whether this result was observed because multiple mating provided genetically compatible sperm or because it provided sufficient sperm. Viability of larvae from multiply mated females was higher than that of larvae from singly mated females, but the total number of adult offspring produced was not significantly different between the two groups. The capacity of males to inseminate females decreased in successive matings after the initial copulation, suggesting that ineffective copulations between virgin females and nonvirgin males are likely due to male sperm depletion. Therefore, mating with multiple males increased the probability that females would produce offspring and served as fertility assurance.
Variation in tiger salamander density within prairie potholes affects aquatic bird foraging behaviour
Authors: Benoy Glenn A
Published: September 2005

Through competitive asymmetry, coexisting fish populations can alter aquatic bird distributions and reduce the reproductive success of their offspring. Gray tiger salamanders (Ambystoma mavortium diaboli Dunn, 1940) may function similarly in fishless prairie potholes. To test the hypothesis that tiger salamanders compete with aquatic birds (including ducks, grebes, and American Coot (Fulica americana J.F. Gmelin, 1789)) for prey resources during the breeding season, 16 potholes were divided into halves by an impermeable plastic barrier and tiger salamander densities were increased or decreased on opposite sides of the barrier. From late May until early July, aquatic invertebrates were sampled from both sides of the divider and the foraging activities of birds were observed. Invertebrate samples revealed that densities of most macroinvertebrate taxa were lower in the halves of potholes with relatively higher densities of tiger salamanders. On average, bird occupancy was evenly distributed on either side of the divider. In contrast, birds spent 65% more time foraging where tiger salamander densities were low (71.2% of total time observed) than where they were high (46.2% of total time observed). The birds most responsive to differences in tiger salamander density and food availability were dabbling ducks, followed by American Coot and diving ducks. This ranking corresponds to the degree of dietary overlap documented between tiger salamanders and aquatic bird assemblages in the study area.
Habitat selection by the Puerto Rican yellow-chinned anole,Anolis gundlachi
Authors: Rodríguez-Robles Javier A , Leal Manuel , Losos Jonathan B
Published: September 2005

Habitat selection can directly affect the fitness of an individual and the evolutionary dynamics of the population to which that organism belongs. We studied habitat use of the Puerto Rican yellow-chinned anole (Anolis gundlachi Peters, 1876) to examine whether this arboreal lizard uses its environment in a nonrandom manner. Males and females preferred woody vegetation substrates over nonwoody plants and sierra palms (Prestoea acuminata var. montana (Graham) A. Henderson and G. Galeano) as perching sites, and they also selected wider vegetation than what was randomly available. Selection for minimizing conspicuousness to potential predators and for increased locomotion capacity may help explain the preference for woody substrates and broader surfaces, respectively. Anolis gundlachi relies almost exclusively on visual cues for foraging and social interactions, and using wider perches also increases an individual's ability to scan a larger proportion of its territory. Our findings thus indicate that the nonrandom habitat use of free-ranging A. gundlachi leads to the selection of perching substrates that may increase performance of ecologically relevant capabilities.
Carbon, nitrogen, and sulfur diet–tissue discrimination in mouse tissues
Authors: Arneson Lynne S , MacAvoy Stephen E
Published: September 2005

Stable-isotope ratios are increasingly being used to examine ecological questions pertaining to dietary choices, physiological status, and animal migration. It has been shown that animal tissues reflect the isotopic signature present in food, altered by a small reproducible fractionation value. The average diet–tissue discrimination for δ13C and δ15N is approximately 1‰ and 3‰, respectively, although the degree of diet–tissue discrimination may be affected by a range of factors and vary between organisms and tissue types. Although the average δ34S is approximately zero, the sulfur diet–tissue discrimination values have only been determined for a few organisms. It is necessary to determine accurate diet–tissue discrimination values between tissue and dietary components to have confidence in any food-web study or determination of diet quality. In this paper, we determine carbon, nitrogen, and sulfur diet–tissue discrimination values for whole blood, liver, skeletal muscle, heart, brain, and fat (carbon only) from adult mice (Mus musculus L., 1758) equilibrated on three diets with unique isotopic signatures for carbohydrate carbon and for protein carbon, nitrogen, and sulfur. These data will aid researchers in choosing tissues to be used to examine food-web changes over time.
Time budget and diving behaviour of chick-rearing Crozet shags
Authors: Tremblay Y , Cook T R , Cherel Y
Published: September 2005

Blue-eyed shags are known to be capable of the deepest dives in the cormorant family. Yet, the way these birds balance their energy and time budgets remains enigmatic. Using ventrally attached time–depth recorders on chick-rearing Crozet shags (Phalacrocorax melanogenis Blyth, 1860), we simultaneously described their time budget and diving behaviour. Crozet shags are diurnal, benthic foragers (mean foraging range 1.7 km) that spend 37% of the daytime at sea. While at sea, they spend 49% of their time on the water, 44% diving, and 7% flying, and consume mainly benthic nototheniid fish. Larger fish (>20 g) were caught at shallower depths during shorter trips. They made, on average, 4.4 trips/day, each including 2.5 diving periods of 14 dives. On average, Crozet shags dove to 28 m (max. 145 m) for 2 min 2 s (max. 6 min 11 s). Descent and ascent rates became less variable at a depth of 40 m, possibly owing to a change in bird relative buoyancy at that depth. Ten percent of dives exceeded the estimated behavioural aerobic dive limit (4 min) and diving depths showed a bimodal distribution at <5 and ~18 m for dives lasting ~1 min. This dive duration corresponded to dives with higher dive duration/postdive interval ratios. The Crozet shags managed their dive cycle to fully exploit their breathing capacities, thus optimizing foraging performance.
FINANCIAL RATIO ANALYSIS OF THE ELECTRIC POWER INDUSTRY
Authors: SUEYOSHI TOSHIYUKI
Published: September 2005

Financial Ratio Analysis is newly proposed to examine the financial performance of the American power/energy industry. The new approach compares the financial performances of 147 non-default firms with those of 24 default firms in the US power/energy market. The proposed approach is a new type of nonparametric discriminant analysis that provides a set of weights of a linear discriminant function, consequently yielding an evaluation score for group membership. Such weight estimates, along with an evaluation score, of the discriminant function provide a total financial evaluation measure, based upon which we can determine the financial performance of the power/energy firms. This empirical study informs that both leverage (debt) and profitability (returns on equity) are important financial factors in terms of avoiding corporate distress or bankruptcy. The empirical results obtained from the American power/energy industry are further extended to the international comparison of other major industrial nations including Japan and the European nations. The international comparison concludes that Japanese electric power firms have enough managerial and financial capabilities even if the American financial standard is hypothetically introduced into the evaluation of their financial performances. However, the empirical results also indicate that the Japanese power industry performs barely above the American standard. Thus, corporate leaders in the Japanese power industry need to pay more serious attention to their corporate finances and financial strategies. Such financial perspective will be increasingly important along with the current deregulation policy of the Japanese government.
SCHEDULING THE HARVESTING OPERATIONS OF A FOREST BLOCK: A CASE STUDY
Authors: CORNER J. L. , FOULDS L. R.
Published: September 2005

We discuss the harvesting of a single forest block from an operations scheduling viewpoint. We report on a harvesting case study, based on practical data from a commercial enterprise, involving minimum and maximum time lags and resource constraints. It appears that the scheduling of the harvesting forest blocks is a significantly different scenario from those represented by the scheduling models available in the literature. The differences come about because: the duration of each operation is dependent upon the combination of constrained resources allocated to it, individual worker-equipment allocation is restricted, and minimum or maximum time lags can be imposed. We report on harvesting operations, a scheduling model, and solution procedures, designed specifically for the case study.
ANNEALING EFFECTS IN PIT-PROCESSED MgB2/SUS316 (STAINLESS STEEL) COMPOSITE WIRES
Authors: BALAMURUGAN S. , HIGASHIKAWA K. , NAKAMURA T. , OSAMURA K.
Published: September 2005

The MgB 2/ SUS316 (stainless steel) wires were fabricated by powder-in-tube (PIT) method using commercially available superconducting MgB 2 powder at ambient pressure, and the annealing effects on Tc as well as Jc were investigated. The as-rolled MgB 2/ SUS316 wire showed a zero-resistance superconducting transition temperature (Tc) at 33.4 K and a critical current density [Formula: see text] of 2.22 kAcm-2 at 18.4 K. In order to check the annealing effect, the different pieces of the as-rolled wires were annealed at various annealing conditions under Ar atmosphere in vacuum (60 cm Hg) sealed silica-tube. As compared to the MgB 2/ Fe wires, the annealing temperature and duration were lower and much shorter respectively, for the MgB 2/ SUS316 (stainless steel) wires. On annealing at 873 K for ~ 1 s, we obtained the best sample with a [Formula: see text] of 12.1 kAcm-2 at 16.9 K with a maximum Tc of 36.1 K. Longer annealing time (~ 10 s) above 873 K reduced the Tc as well as the Jc, indicating a possible chemical reaction between the MgB 2 cores and the sheath material.
Endothelin-1 increases intracellular Ca2+in rabbit pulmonary artery smooth muscle cells through phospholipase C
Authors: Ko Eun A. , Park Won Sun , Ko Jae-Hong , Han Jin , Kim Nari , Earm Yung E.
Published: September 2005

In freshly isolated rabbit pulmonary artery smooth muscle cells, endothelin (ET)-1 induced a transient increase in intracellular Ca2+concentration ([Ca2+]i) followed by a return to the initial [Ca2+]i. This response was not abolished by the voltage-dependent Ca2+channel blocker nicardipine or removal of Ca2+from the bath solution but was inhibited by ryanodine and thapsigargin. This finding suggested that the increase in [Ca2+]iinduced by ET-1 was attributable to release of Ca2+from ryanodine- and inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+stores. The transient increase in [Ca2+]iinduced by ET-1 was also inhibited by pretreatment with antagonists of ET type A and B (ETAand ETB) receptors (BQ-123 and BQ-788, respectively). Furthermore, the ETBreceptor agonist IRL-1620 induced an increase in [Ca2+]ithat was followed by a sustained increase in [Ca2+]i; the sustained increase in [Ca2+]iwas blocked by nicardipine. Using the nystatin-perforated patch-clamp technique, we found that IRL-1620 caused an increase in Ca2+current that was inhibited by addition of ET-1. ET-1 did not inhibit Ca2+current when cells were pretreated with BQ-123. These results suggested that when both receptor types are activated, the opposing responses lead to abolition of the sustained [Ca2+]iincreases induced by ETBreceptor activation. Western blot analysis confirmed expression of ETAand ETBreceptors. Finally, U-73122 inhibited the ET-1-induced [Ca2+]iincrease, indicating that phospholipase C was involved in modulation of the ET-1-induced [Ca2+]iincrease in rabbit pulmonary artery smooth muscle cells.
Ischemic preconditioning increases the bioavailability of cardiac enkephalins
Authors: Younès Antoine , Pepe Salvatore , Yoshishige Darice , Caffrey James L. , Lakatta Edward G.
Published: September 2005

Growing evidence suggests that cardiac enkephalins and their receptors are involved in ischemic preconditioning (IPC). Because there is no evidence for vesicular storage of small bioactive enkephalins in the heart, studies were designed to test the hypothesis that ischemia depletes cardiac enkephalins and that IPC preserves the same enkephalins by accelerating their processing from the larger proenkephalin precursor (PEP) pool. The precursors and two bioactive representatives, Met-enkephalin (ME) and Met-enkephalin-Arg-Phe (MEAP), were separated by size-exclusion chromatography and quantified by radioimmunoassay. Isolated perfused rat hearts were prepared and exposed to global ischemia. After 30 min of global ischemia and 40 min of reflow, the PEP pool was reduced (from 17.99 ± 1.52 to 14.20 ± 2.38 pmol/g wet wt), MEAP increased by 53%, and ME declined by 68%. The sum of the two smaller peptides was unchanged (9.78 ± 0.83 vs. 9.33 ± 2.81). Thus the total enkephalin peptide content was not altered (27.77 ± 1.69 vs. 24.10 ± 4.75). Peptide distribution after ischemia and reflow was also unaltered by pretreatment with peptidase inhibitors. However, when the hearts were preconditioned, the PEP pool remained significantly lower and both of the bioactive peptides, MEAP and ME, were elevated (+49% and +86%, respectively). The decline in the PEP pool was prevented by peptidase inhibition and the rise in MEAP was exaggerated. In separate protocols, synthetic enkephalins (ME, MEAP, and Leu-enkephalin) were added to the coronary inflow before 30 min of global ischemia and throughout the subsequent reflow. The added enkephalins (10−8M) had no inotropic effect on baseline function but completely prevented the mechanical dysfunction observed in untreated controls during reflow. Thus IPC appears to increase available bioactive enkephalins (MEAP + ME) within the heart by enhancing synthesis of precursors and their subsequent processing from the PEP pool.
Estrogen-induced contraction of coronary arteries is mediated by superoxide generated in vascular smooth muscle
Authors: White Richard E. , Han Guichun , Dimitropoulou Christiana , Zhu Shu , Miyake Katsuya , Fulton David , Dave Shaylee , Barman Scott A.
Published: September 2005

Although previous studies demonstrated beneficial effects of estrogen on cardiovascular function, the Women's Health Initiative has reported an increased incidence of coronary heart disease and stroke in postmenopausal women taking hormone replacement therapy. The objective of the present study was to identify a molecular mechanism whereby estrogen, a vasodilatory hormone, could possibly increase the risk of cardiovascular disease. Isometric contractile force recordings were performed on endothelium-denuded porcine coronary arteries, whereas molecular and fluorescence studies identified estrogen signaling molecules in coronary smooth muscle. Estrogen (1–1,000 nM) relaxed arteries in an endothelium-independent fashion; however, when arteries were pretreated with agents to uncouple nitric oxide (NO) production from NO synthase (NOS), estrogen contracted coronary arteries with an EC50 of 7.3 ± 4 nM. Estrogen-induced contraction was attenuated by reducing superoxide (O2−). Estrogen-stimulated O2− production was detected in NOS-uncoupled coronary myocytes. Interestingly, only the type 1 neuronal NOS isoform (nNOS) was detected in myocytes, making this protein a likely target mediating both estrogen-induced relaxation and contraction of endothelium-denuded coronary arteries. Estrogen-induced contraction was completely inhibited by 1 μM nifedipine or 10 μM indomethacin, indicating involvement of dihydropyridine-sensitive calcium channels and contractile prostaglandins. We propose that a single molecular mechanism can mediate the dual and opposite effect of estrogen on coronary arteries: by stimulating type 1 nNOS in coronary arteries, estrogen produces either vasodilation via NO or vasoconstriction via O2−.
Aldosterone increases urine production and decreases apical AQP2 expression in rats with diabetes insipidus
Authors: Nielsen Jakob , Kwon Tae-Hwan , Praetorius Jeppe , Frøkiær Jørgen , Knepper Mark A. , Nielsen Søren
Published: September 2005

Vasopressin and aldosterone are essential hormones in the regulation of water and sodium balance. Aldosterone regulates sodium reabsorption, although synergistic effects on collecting duct water permeability have been shown. We investigated the effects of 7-day aldosterone infusion or oral spironolactone treatment on water balance and aquaporin (AQP) 2 expression in rats with 21 days of lithium-induced nephrogenic diabetes insipidus (Li-NDI). In rats with Li-NDI, aldosterone markedly increased (271 ± 14 ml/24 h), whereas spironolactone decreased (74 ± 11 ml/24 h) urine production compared with rats treated with lithium only (120 ± 11 ml/24 h). Aldosterone increased free-water clearance and creatinine clearance, whereas spironolactone caused a decreased creatinine clearance but unchanged free-water clearance. Immunoblotting showed unchanged AQP2 expression in cortex/outer stripe of the outer medulla and inner medulla. In the inner stripe of the outer medulla aldosterone caused a decreased AQP2 expression, whereas spironolactone caused an increase compared with rats treated with lithium only. Semiquantitative confocal immunofluorescence microscopy of AQP2 immunolabeling showed reduced AQP2 expression in the apical plasma membrane domain in connecting tubule (CNT) and initial cortical collecting ducts (iCCD) in response to aldosterone-treated rats compared with rats treated with lithium only. Spironolactone significantly increased apical AQP2 expression in the iCCD compared with rats treated with lithium only. We also tested whether similar changes could be observed in vasopressin-deficient BB rats and found similar changes in urine production and subcellular AQP2 expression in the CNT and iCCD in response to aldosterone and spironolactone. This study shows that aldosterone treatment perturbs diabetes insipidus and is associated with AQP2 redistribution in CNT and iCCD likely mediated by the spironolactone-sensitive mineralocorticoid receptor.
Anti-inflammatory effects of short-term pioglitazone therapy in men with advanced diabetic nephropathy
Authors: Agarwal Rajiv
Published: September 2005

Patients with diabetic nephropathy have a high rate of cardiovascular events and mortality. Nontraditional cardiovascular risk factors such as oxidative stress and inflammation are thought to be particularly important in mediating these events. Studies suggest that thiazolidinediones (TZDs) can reduce the level of nontraditional cardiovascular risk in people with or without diabetes mellitus. Whether this benefit occurs in patients with diabetic nephropathy is unknown. I hypothesized that the TZD pioglitazone will mitigate oxidative stress and inflammation compared with glipizide in patients with overt diabetic nephropathy. Markers of oxidative stress (plasma and urine albumin carbonyl and total protein carbonyls and malondialdehyde), inflammation [white blood cell (WBC) count, C-reactive protein (CRP), plasma IL-6, TNF-α], and plaque stability [matrix metalloproteinase 9 (MMP-9)] were measured in frozen samples obtained from patients with overt diabetic nephropathy participating in a randomized, open-label, blinded end-point, 16-wk trial with glipizide ( n = 22) or pioglitazone ( n = 22). Pioglitazone therapy in men with advanced diabetic nephropathy reduced WBC count by 1,125/μl ( P < 0.001), CRP by 41% ( P = 0.042), IL-6 by 38% ( P = 0.009), and MMP-9 by 29% ( P = 0.016). Specific differential reductions in WBC count of 1,251/μl ( P = 0.009) and reduction in IL-6 of 58% with pioglitazone ( P = 0.001) were seen compared with glipizide. There were no statistically significant changes observed with plasma TNF-α concentrations or markers of oxidative stress with either hypoglycemic agent. In conclusion, pioglitazone reduces proinflammatory markers in patients with overt diabetic nephropathy, which indicates potentially beneficial effects on overall cardiovascular risk. This surrogate end point needs to be confirmed in trials designed to demonstrate cardiovascular protection.
Hypotension inNKCC1null mice: role of the kidneys
Authors: Wall Susan M. , Knepper Mark A. , Hassell Kathryn A. , Fischer Michael P. , Shodeinde Adetola , Shin Wonkyong , Pham Truyen Derek , Meyer Jamie W. , Lorenz John N. , Beierwaltes William H. , Dietz John R. , Shull Gary E. , Kim Young-Hee
Published: September 2005

NKCC1 null mice are hypotensive, in part, from the absence of NKCC1-mediated vasoconstriction. Whether these mice have renal defects in NaCl and water handling which contribute to the hypotension is unexplored. Therefore, we asked 1) whether NKCC1 ( −/−) mice have a defect in the regulation of NaCl and water balance, which might contribute to the observed hypotension and 2) whether the hypotension observed in these mice is accompanied by endocrine abnormalities and/or downregulation of renal Na+transporter expression. Thus we performed balance studies, semiquantitative immunoblotting, and immunohistochemistry of kidney tissue from NKCC1 ( +/+) and NKCC1 ( −/−) mice which consumed either a high (2.8% NaCl)- or a low-NaCl (0.01% NaCl) diet for 7 days. Blood pressure was lower in NKCC1 ( −/−) than NKCC1 ( +/+) mice following either high or low dietary NaCl intake. Relative to wild-type mice, NKCC1 null mice had a lower plasma ANP concentration, a higher plasma renin and a higher serum K+concentration with inappropriately low urinary K+excretion, although serum aldosterone was either the same or only slightly increased in the mutant mice. Expression of NHE3, the α-subunit of the Na-K-ATPase, NCC, and NKCC2 were higher in NKCC1 null than in wild-type mice, although differences were generally greater during NaCl restriction. NKCC1 null mice had a reduced capacity to excrete free water than wild-type mice, which resulted in hypochloremia following the NaCl-deficient diet. Hypochloremia did not occur from increased aquaporin-1 (AQP1) or 2 protein expression or from redistribution of AQP2 to the apical regions of principal cells. Instead, NKCC1 null mice had a blunted increase in urinary osmolality following vasopressin administration, which should increase free water excretion and attenuate the hypochloremia. In conclusion, aldosterone release is inappropriately low in NKCC1 null mice. Moreover, the action of aldosterone and vasopressin is altered within kidneys of NKCC1 null mice, which likely contributes to their hypotension. Increased Na+transporter expression, increased plasma renin, and reduced plasma ANP, as observed in NKCC1 null mice, should increase vascular volume and blood pressure, thus minimizing hypotension.
Astrocytic Glutamate Release-Induced Transient Depolarization and Epileptiform Discharges in Hippocampal CA1 Pyramidal Neurons
Authors: Kang Ning , Xu Jun , Xu Qiwu , Nedergaard Maiken , Kang Jian
Published: September 2005

A paroxysmal depolarization shift (PDS) has been suggested to be a hallmark for epileptic activity in partial-onset seizures. By monitoring membrane potentials and currents in pairs of pyramidal neurons and astrocytes with dual patch-clamp recording and exocytosis of vesicles from astrocytes with two-photon laser scanning microscopy in hippocampal slices, we found that infusion of inositol 1,4,5-trisphosphate (IP3) into astrocytes by patch pipettes induced astrocytic glutamate release that triggered a transient depolarization (TD) and epileptiform discharges in CA1 pyramidal neurons. The TD is due to a tetrodotoxin (TTX)-insensitive slowly decaying transient inward current (STC). Astrocytic glutamate release simultaneously triggers both the STC in pyramidal neurons and a transport current (TC) in astrocytes. The neuronal STC is mediated by ionotropic glutamate receptors leading to the TD and epileptiform discharges; while the astrocytic TC is a glutamate reuptake current resulting from transporting released glutamate into the patched astrocyte. Fusion of a large vesicle in astrocytes was immediately followed by an astrocytic TC, suggesting that the fused vesicle contains glutamate. Both fusion of large vesicles and astrocytic TCs were blocked by tetanus toxin (TeNT), suggesting that astrocytic glutamate release is via SNARE-dependent exocytosis of glutamate-containing vesicles. In the presence of TTX, the epileptogenic reagent, 4-AP, also induced similar neuronal STCs and astrocytic TCs, suggesting that astrocytic glutamate release may play an epileptogenic role in initiation of epileptic seizures under pathological conditions. Our study provides a novel mechanism, astrocytic release of glutamate, for seizure initiation.
Limb Movements During Embryonic Development in the Chick: Evidence for a Continuum in Limb Motor Control Antecedent to Locomotion
Authors: Bradley Nina S. , Solanki Dhara , Zhao Dawn
Published: September 2005

New imaging technologies are revealing ever-greater details of motor behavior in fetuses for clinical diagnosis and treatment. Understanding the form, mechanisms, and significance of fetal behavior will maximize imaging applications. The chick is readily available for experimentation throughout embryogenesis, making it an excellent model for this purpose. Yet in 40 yr since Hamburger and colleagues described chick embryonic behavior, we have not determined if motility belongs to a developmental continuum fundamental to posthatching behavior. This study examined kinematics and synchronized electromyography (EMG) during spontaneous limb movements in chicks at four time points between embryonic days (E) 9–18. We report that coordinated kinematic and/or EMG patterns were expressed at each time point. Variability observed in knee and ankle excursions at E15–E18 sorted into distinct in-phase and out-of-phase patterns. EMG patterns did not directly account for out-of-phase patterns, indicating study of movement biomechanics will be critical to fully understand motor control in the embryo. We also provide the first descriptions of 2- to 10-Hz limb movements emerging E15–E18 and a shift from in-phase to out-of-phase interlimb coordination E9–E18. Our findings revealed that coordinated limb movements persist across development and suggest they belong to a developmental continuum for locomotion. Limb patterns were consistent with the half center model for a locomotor pattern generator. Achievement of these patterns by E9 may thus indicate the embryo has completed a critical phase beyond which developmental progression may be less vulnerable to experimental perturbations or prenatal events.
Serum alkaline phosphatase activity is regulated by a chromosomal region containing the alkaline phosphatase 2 gene (Akp2) in C57BL/6J and DBA/2J mice
Authors: Foreman Jennifer E. , Blizard David A. , Gerhard Glenn , Mack Holly A. , Lang Dean H. , Van Nimwegen Kathryn L. , Vogler George P. , Stout Joseph T. , Shihabi Zakariya K. , Griffith James W. , Lakoski Joan M. , McClearn Gerald E. , Vandenbergh David J.
Published: September 2005

Quantitative trait locus (QTL) analyses were conducted to identify chromosomal regions that contribute to variability in serum alkaline phosphatase (AP) enzyme activity in mice derived from the C57BL/6J (B6) and DBA/2J (D2) inbred strains. Serum AP was measured in 400 B6D2 F2mice at 5 mo and 400 B6D2 F2mice at 15 mo of age that were genotyped at 96 microsatellite markers, and in 19 BXD recombinant inbred (RI) strains at 5 mo of age. A QTL on the distal end of chromosome 4 was present in all sex- and age-specific analyses with a peak logarithm of odds (LOD) score of 20.36 at 58.51 cM. The Akp2 gene, which encodes the major serum AP isozyme, falls within this QTL region at 70.2 cM where the LOD score reached 13.2 (LOD significance level set at 4.3). Serum AP activity was directly related to the number of D2 alleles of a single nucleotide polymorphism in the 5′-flanking region of the Akp2 gene, although no strain-related differences in hepatic expression of Akp2 RNA were found. A variety of sequence polymorphisms in this chromosomal region could be responsible for the differences in serum AP activity; the Akp2 gene, however, with several known amino acid substitutions between protein sequences of the B6 and D2 strains, is a leading candidate.
Cross-Cultural and Historical Perspectives on the Developmental Consequences of Education
Authors: Cole Michael
Published: September 2005

The goal of this paper is to examine efforts to understand the developmental consequences, particularly the cognitive consequences, of children spending large amounts of time in formal schools where their activity is separated from the daily life of the rest of the community and mediated by technologies of literacy and numeracy as well as specialized uses of language. The analysis begins by examining the history of formal schooling in relation to its social and cultural circumstances and progresses through an examination of different research strategies for reaching plausible conclusions about its cognitive consequences in the sociocultural context. The discussion ends by considering two contradictory tendencies, centralized standardization versus de-centralized adaptation and separation versus embeddedness, which have characterized education since its inception and which societies around the world confront in our current historical circumstances.
Identity as a Source of Moral Motivation
Authors: Hardy Sam A. , Carlo Gustavo
Published: September 2005

Theory and research regarding moral motivation has focused for decades on the roles of moral reasoning and, to some extent, moral emotion. Recently, however, several models of morality have positioned identity as an additional important source of moral motivation. An individual has a moral identity to the extent that he or she has constructed his or her sense of self around moral concerns (e.g., moral values). This paper reviews theory and research linking moral identity to moral behavior and commitment. Additionally, it suggests several key unanswered questions about moral identity and provides recommendations for future research.
The Future Role of Thalidomide in Multiple Myeloma
Authors: Boccadoro Mario , Blade Joan , Attal Michel , Palumbo Antonio
Published: September 2005

Treatment for multiple myeloma typically is chemotherapy, high-dose therapy with stem cell transplantation or radiation. Thalidomide shows promise, but to improve knowledge and understanding of this drug, more clinical data is required. Workshops designed to propose new studies providing much needed data on the use of thalidomide as first-line therapy, as maintenance therapy and as treatment for refractory or relapsed disease are reported here. Thalidomide has been shown to be effective in previously untreated patients as monotherapy (36% remission), although greater remission is seen in combination therapy, for example, thalidomide with dexamethasone (72% remission). Thalidomide is an interesting maintenance therapy. It has the advantages of being effective in the bone marrow and having a long-lasting effect but suffers because of its significant side-effect profile; however, it is tolerated by most patients. The adverse effects are thought to be dose-limiting, and most are seen in all patients at the beginning of treatment. Further clinical evidence is needed to determine the effectiveness of thalidomide as maintenance therapy in patients with multiple myeloma, having been shown to be active against refractory multiple myeloma, even in patients who relapse after high-dose chemotherapy. The workshop acknowledged the problems associated with designing a phase III study, and it is clear that many areas need to be addressed in the use of thalidomide for the treatment of multiple myeloma.
Future Directions in Haematology: Beyond Multiple Myeloma
Authors: Prentice H. Grant , Sacchi Stephano , Russell Nigel
Published: September 2005

Thalidomide acts on the microenvironment of myelodysplastic syndromes (MDS) by influencing cytokine networks, and growing evidence supports thalidomide’s usefulness in the management of haematological malignancies, such as MDS. The European Collaboration Group on Myelofibrosis with Myeloid Metaplasia reviewed patients who received at least four weeks’ thalidomide treatment, in doses ranging from 50 mg/day to 400 mg/day. The results showed that 30% of patients had increases in haemoglobin, and, of these, almost 40% became transfusion independent. Platelets were increased in a significant proportion of patients, and approximately 40% of patients had a reduction in their spleen size. Data on thalidomide and acute myeloblastic leukaemia (AML) are conflicting: a recently published study indicated that thalidomide does not have a role in the management of acute myeloblastic leukaemia (AML), while other studies suggest some patients may respond because of thalidomide’s ability to activate natural killer cells and cytotoxic T-lymphocytes. Partial responses to thalidomide treatment have been recorded in patients with lymphoma. In a phase II study to assess the activity of thalidomide in patients with Waldenström’s macroglobulinaemia, a partial response was seen in 25% of patients who received a starting dose of 200 mg, which was escalated in 200 mg increments every 14 days as tolerated to a maximum of 600 mg. Although further study is required, thalidomide shows promise in the treatment of a number of haematological malignancies, many of which currently have limited treatment options and poor prognosis.
Viral Hepatitis C in Hong Kong
Authors: Leung Nancy , Chu Carol M.C. , Tam John S.
Published: September 2005

Objective: Hepatitis C virus (HCV) infection can lead to serious liver disease. Its medico-socio-economic burden on society can be immense. This study investigates the epidemiology of HCV infection in Hong Kong. Methods: Data from the Department of Health, relevant publications from Medline search and data from two acute hospitals were reviewed. Results: The prevalence of anti-HCV among voluntary blood donors is stable, remaining at approximately 0.035–0.099% over the past 10 years, and is higher in the older age group. Among the high-risk groups, the anti-HCV prevalence is as follows: (1) hospital patients 0.8%, (2) intravenous drug users 46.0%, (3) patients infected with HIV 7.9%, (4) children with transfusion-dependent hematologic disease 16.3%, (5) patients on continuous ambulatory peritoneal dialysis 1.8%, patients on hemodialysis 16.4%, recipients of kidney transplants 6.2% and (6) patients with hepatocellular carcinoma 7.3%. Among blood donors, 58.8% were infected with HCV genotype 1b and 27.0% with genotype 6a. Genotype 6a is particularly common among intravenous drug users. Conclusion: Hong Kong has a low prevalence of HCV infection. Patients are mostly infected through transfusion with blood or products prior to the introduction of anti-HCV screening to the blood transfusion service. Illicit drug use constitutes another significant risk. Since 1997, there has been a great increase in population movement between China and Hong Kong which might affect the epidemiology of HCV infection.
Impaired Function of Dendritic Cells Circulating in Patients Infected with Hepatitis C Virus Who Have Persistently Normal Alanine Aminotransferase Levels
Authors: Kanto Tatsuya , Inoue Michiyo , Miyazaki Masanori , Itose Ichiyo , Miyatake Hideki , Sakakibara Mitsuru , Yakushijin Takayuki , Kaimori Aki , Oki Chika , Hiramatsu Naoki , Kasahara Akinori , Hayashi Norio
Published: September 2005

Hepatitis C virus (HCV) induces chronic liver disease in hosts which can eventually progresses to liver cirrhosis and hepatocellular carcinoma. However, progression of liver disease is slower in patients with persistently normal levels of alanine aminotransferase (ALT) than in those with active hepatitis. Although distinct immune responses against HCV have been proposed in asymptomatic infection, the role of circulating dendritic cells (DC) in the pathogenesis of these patients remains obscure. To address this issue, we compared the number and function of myeloid DC (MDC) and plasmacytoid DC (PDC) between uninfected individuals and HCV-infected patients with or without elevated ALT levels. Numbers of DC and DC progenitors were significantly lower in patients with chronic active hepatitis than in control subjects. However, no differences were found in the number of DC between normal controls and HCV-infected patients with persistently normal ALT levels. MDC from patients with active hepatitis were less able to polarize naive CD4 T cells into the Th1 phenotype, while their MDC and PDC primed more CD4 T cells producing IL-10 than those from normal controls. Such dysfunction of DC was also observed in patients with persistently normal ALT levels. In conclusion, circulating DC decrease in number predominantly in HCV-infected patients with active hepatitis, and the function of DC is impaired even in those with normal ALT levels.
Treatment of Chronic Hepatitis C in Southern Taiwan
Authors: Chuang Wang-Long , Yu Ming-Lung , Dai Chia-Yen , Chang Wen-Yu
Published: September 2005

Chronic hepatitis C virus (HCV) infection may lead to cirrhosis and hepatocellular carcinoma. Interferon (IFN)-α is effective in the treatment of chronic hepatitis C. The rate of response to IFN is enhanced by increasing the IFN dose. Extending the treatment duration can reduce the relapse rate. Addition of ribavirin to IFN increases the sustained virological response (SVR). Thus, combination therapy with IFN and ribavirin was adopted for the treatment of chronic hepatitis C in Kaohsiung Medical University Hospital in 1998. Approximately 60% of patients receiving IFN/ribavirin therapy gained SVR. IFN 6 million units three times per week combined with daily ribavirin for 6 months achieved SVR more frequently than combination therapy with 3 million units. Factors for SVR in these combination regimens were HCV genotype, viral load and early virological response. Long-term follow-up of patients treated with IFN has shown that SVR might reduce the risk of progression to cirrhosis and hepatocellular carcinoma. Pegylated (peg)-IFN has a longer half-life and better efficacy. Combination therapy with peg-IFN and ribavirin accomplished higher SVR than conventional IFN and ribavirin. A multicenter clinical trial was conducted in Taiwan to compare the efficacy of combination therapy between peg-IFN/ribavirin and conventional IFN/ribavirin for 6 months. SVR was higher in patients receiving peg-IFN and ribavirin, especially in those infected with HCV genotype 1b. Based on the results obtained, the national health insurance started to sponsor the combination therapy in October 2003, with a suggested duration for 6 months. Some small-scale studies in Taiwan have postulated higher SVR for treatment duration of 12 than of 6 months in patients with genotype 1b. Further investigation should be conducted in the near future.
Single-Nucleotide Polymorphisms and Haplotype LD Analysis of the 29-kb IGF2 Region on Chromosome 11p15.5 in the Korean Population
Authors: Lee Hye-Ja , Kim Kwang-Joong , Park Mi-Hyun , Kimm Kuchan , Park Chan , Oh Bermseok , Lee Jong-Young
Published: September 2005

Objective: We investigated sequence variations of the 29-kb insulin-like growth factor 2 (IGF2) region in human chromosome region 11p15.5 in the Korean population. This region consists of IGF2, insulin-like growth factor 2 antisense (IGF2AS), and the insulin gene, all important candidate genes for various diseases, including cancer, obesity, diabetes, and coronary disease. While single nucleotide polymorphisms (SNPs) have been identified for this region and used in association studies, ethnic differences in genetic variation at this site have not been addressed. To date, SNPs for the entire 29-kb region in the Korean population have not been reported. Methods: We surveyed a population of 108 Koreans for SNPs in the 29-kb IGF2 region. Results: We identified 62 SNPs, consisting of 6 SNPs in the promoter region, 17 in the untranslated region, 19 in introns, and 20 in the intergenic region. We also analyzed linkage disequilibrium (LD) patterns and haplotypes using 36 high-frequency (> 5%)SNPs and found a well-defined LD block spanning about 13 kb that includes 8 kb of the IGF2AS gene, with two hot-spot regions flanking the LD block. Conclusion: These SNPs may be useful as genetic markers in disease association studies in the Korean population.
Wine Ingestion Has No Effect on Lipid Peroxidation Products
Authors: Ziegler Sophie , Kostner Karam , Thallinger Christiane , Bur Andreas , Brunner Martin , Wolzt Michael , Joukhadar Christian
Published: September 2005

Objective: Moderate alcohol consumption has been associated with beneficial effects on coronary heart disease. This positive effect has been partly attributed to the flavonol contents which promote vasodilatory, anti-aggregatory and antioxidative effects and protect low-density lipoprotein (LDL) cholesterol from oxidation. Thus, the present study was carried out to determine the acute effects of different wines on LDL oxidization in healthy volunteers. Methods: Healthy male and female subjects (15/group) on a flavonol-restricted diet were randomly assigned to drink 300 ml wine from one of four different grapes and fermentation processes. Conjugated fatty acid dienes and thiobarbituric acid reactive substances (TBARS) were determined as a measure of LDL oxidation in serum at baseline and up to 96 h after wine ingestion. Results: At baseline, mean conjugated dienes in serum were 12.5 ± 6.2 µmol/l and mean TBARS in serum were 15.7 ± 8.1 µmol/l. There were no differences between the groups and no effect of any wine type on conjugated dienes (p = 0.15) or TBARS (p = 0.38) over time. 96 h following wine ingestion, the mean conjugated dienes were 12.1 ± 4.12 µmol/l and mean TBARS were 16.4 ± 8.8 µmol/l (pooled data, n = 60). Conclusion: Ingestion of 300 ml wine does not protect LDL from oxidation in vivo in healthy subjects. However, this does not exclude an effect of habitual wine consumption on LDL plasma oxidation.