bluuebunny/crossref_metadata_2025 huggingface dataset:
Rotator cuff tendinopathy
Authors: Lewis J S
Published: September 2008

Purpose:

A review was conducted to synthesise the available research literature on the pathogenesis of rotator cuff tendinopathy.

Relevance:

Musculoskeletal disorders of the shoulder are extremely common, with reports of prevalence ranging from one in three people experiencing shoulder pain at some stage of their lives to approximately half the population experiencing at least one episode of shoulder pain annually. Pathology of the soft tissues of the shoulder, including the musculotendinous rotator cuff and subacromial bursa, is a principal cause of pain and suffering.

Conclusions:

The pathoaetiology of rotator cuff failure is multifactorial and results from a combination of intrinsic, extrinsic and environmental factors. The specialised morphology of the rotator cuff, together with the effects of stress shielding, may contribute to the development of rotator cuff tendinopathy. Profound changes within the subacromial bursa are strongly related to the pathology and resulting symptoms. A considerable body of research is necessary to more fully understand the aetiology and pathohistology of rotator cuff tendinopathy and its relationship with bursal pathology. Once this knowledge exists more effective management will become available.
Predation by brown trout (Salmo trutta) along a diversifying prey community gradient
Authors: Jensen Hallvard , Kahilainen Kimmo K. , Amundsen Per-Arne , Gjelland Karl Øystein , Tuomaala Antti , Malinen Tommi , Bøhn Thomas
Published: September 2008

Predation has a fundamental role in aquatic ecosystems, but the relative importance of factors governing prey selection by predators remains controversial. In this study, we contrast five lakes of a subarctic watershed to explore how prey community characteristics affect prey selection and growth rate of the common top predator, brown trout ( Salmo trutta ). The lakes constitute a distinct gradient of different coregonid prey fish, ranging from monomorphic common whitefish ( Coregonus lavaretus ) to polymorphic whitefish co-occurring with vendace ( Coregonus albula ). The brown trout was a morph–species- and size-specific pelagic predator, selecting the small-sized, pelagic whitefish morph or vendace over the benthic whitefish morphs. In all lakes, the average prey size increased with predator size, but small-sized prey were also included in the diet of large predators. The selection of small-sized, pelagic prey fish appeared to be a favourable foraging strategy for the brown trout, yielding higher growth rates and an earlier ontogenetic shift to piscivory. The findings emphasize that piscivory appear to be shaped by the diversity, size-structure, and abundance of available prey in a given community.
Potential limits to anthropogenic mortality of small cetaceans in coastal waters of British Columbia
Authors: Williams Rob , Hall Anna , Winship Arliss
Published: September 2008

Small cetaceans are by-caught in salmon gillnet fisheries in British Columbia (BC) waters. In Canada, there is currently no generic calculation to identify when management action is necessary to reduce cetacean bycatch below sustainable limits. We estimated potential anthropogenic mortality limits for harbour ( Phocoena phocoena ) and Dall’s ( Phocoenoides dalli ) porpoises and Pacific white-sided dolphins ( Lagenorhynchus obliquidens ) using quantitative objectives from two well-established frameworks for conservation and management (the United States’ Marine Mammal Protection Act and the Agreement on the Conservation of Small Cetaceans of the Baltic and North Seas), which are similar to some management objectives developed for marine mammal stocks elsewhere in Canada. Limits were calculated as functions of (i) a minimum abundance estimate (2004–2005); (ii) maximum rate of population increase; and (iii) uncertainty factors to account for bias in abundance estimates and uncertainty in mortality estimates. Best estimates of bycatch mortality in 2004 and 2005 exceeded only the most precautionary limits and only for porpoise species. Future research priority should be given to determining small cetacean stock structure in BC and refining species-specific entanglement rates in these and other fisheries. The approach offers a quantitative framework for Canada to meet its stated objectives to maintain favourable conservation status of cetacean populations.
Network models for ecosystem-based fishery analysis: a review of concepts and application to the Gulf of Alaska marine food web
Authors: Gaichas Sarah K. , Francis Robert C.
Published: September 2008

We apply graph theory and network analysis to the food web of the Gulf of Alaska marine ecosystem to classify its structural properties, which suggest how the ecosystem as a whole may respond to heavy fishing pressure on its components. Three conceptual models of network structure, random, small-world, and scale-free, each have different implications for system behavior and tolerance to perturbations. We constructed two food web network models using detailed quantitative information on the stomach contents of 57 predator (fish) species collected during trawl surveys of the Gulf of Alaska between 1981 and 2002. The resulting food webs displayed both small-world and scale-free network properties, suggesting that impacts on one species might spread to many through short interaction chains and that while most food web connections are not critical, a small set of fished species support critical structural connections. Ecosystem-based fishery management should therefore first focus on protecting the highly connected species in the network to avoid structural impacts of fishing on the food web.
Mechanisms underlying the increase in young-of-the-year Atlantic salmon (Salmo salar) density with habitat complexity
Authors: Venter Oscar , Grant James W.A. , Noël Michelle V. , Kim Jae-woo
Published: September 2008

We tested three hypotheses used to explain the increase in young-of-the-year (YOY) Atlantic salmon ( Salmo salar ) density with habitat complexity: the territory-size, predator-refuge, and foraging-benefits hypotheses. We manipulated habitat complexity in three different treatments (boulder-removed, control, and boulder-added) at eight sites in Catamaran Brook and the Little Southwest Miramichi River, New Brunswick. The density of juvenile salmon was two times higher in the boulder-added treatment than in the other treatments. Our data were consistent with the territory-size hypothesis; visual isolation was highest and territory size was smallest in the boulder-added treatment, and salmon selected microhabitats to maximize their field of view. Our results showed partial support for the predator-refuge hypothesis; salmon in the boulder-added sites were closer to cover and showed a reduced reaction distance to a novel stimulus, but did not preferentially select microhabitats closer to cover. We found no direct support for the foraging-benefits hypothesis; however, there is indirect evidence that boulders may improve the growth potential of instream habitat. Our results suggest that YOY Atlantic salmon may be attracted to complex environments for the increased cover and that the decreased visibility of these sites causes a reduction in territory size, allowing a higher density of fish.
Dynamics of bacteria–substrate stable isotope separation: dependence on substrate availability and implications for aquatic food web studies
Authors: McGoldrick Daryl J. , Barton David R. , Power Michael , Scott Ryan W. , Butler Barbara J.
Published: September 2008

Heterotrophic bacteria growing without substrate limitation discriminate against the heavier stable isotopes of C and N, which is reflected in the isotopic signatures of consumers of bacteria. We measured bacteria and substrate isotopic separation (C and N) during glucose and ammonium uptake by three strains of bacteria ( Pseudomonas putida , Bacillus megaterium , and Enterobacter aerogenes ) grown in batch culture at 4 and 30 °C. Isotopic separation between bacteria and substrate was dependent on substrate availability. Higher discrimination against the heavier isotopes, and therefore more depleted δ13C and δ15N values of bacterial biomass, were observed during the exponential growth phase when the nutrient supply was in excess of the demand. We also compared the isotopic ratios of Chironomus tentans grown on aged macrophyte detritus and commercial fish food. Isotopic signatures of Chironomus larvae grown on fish food were within the ranges typical of one trophic step, whereas larvae grown on detritus were strongly depleted in13C, suggesting assimilation of bacteria that had grown on the C-rich detritus. Our results are consistent with the very few other studies of bacterial fractionation of nonlimiting nutrients and may also explain the frequent observation of unexpectedly depleted isotopic signatures in aquatic food web studies.
Quantifying age-reading error for use in fisheries stock assessments, with application to species in Australia’s southern and eastern scalefish and shark fishery
Authors: Punt André E. , Smith David C. , KrusicGolub Kyne , Robertson Simon
Published: September 2008

Age-reading error occurs when estimates of age based on reading hard structures differ from the true age of the animal concerned. This error needs to be accounted for when conducting stock assessments. Common methods for quantifying age-reading error include the average percent error, the coefficient of variation, age bias plots, and age difference tables, but these techniques cannot be used to construct age-reading error matrices. A method for constructing age-reading error matrices that accounts for both ageing bias and ageing imprecision is outlined. Simulation evaluation of this method suggests that it is able to estimate both ageing bias (assuming that one reader is unbiased) and ageing imprecision for relatively large sample sizes and for the ages that constitute the bulk of the ages in the sample. However, the performance of the method is poor when sample sizes are small, age-reading error is correlated among readers, when both readers are biased, and for ages that are poorly represented in the sample. The method is applied for illustrative purposes to data on multiple-aged fish in Australia’s southern and eastern scalefish and shark fishery.
Intralacustrine site fidelity and nonrandom mating in the littoral-spawning northern redbelly dace (Phoxinus eos)
Authors: Massicotte Rachel , Magnan Pierre , Angers Bernard
Published: September 2008

Natal site fidelity of the northern redbelly dace ( Phoxinus eos ), a common minnow in North America, was confirmed by combining ecological and genetic approaches. A 2-year mark–recapture experiment conducted at four sites separated by 50–450 m strongly supported the propensity of the dace to practice site fidelity during the reproductive period. Individuals recaptured at their marking sites were characterized with five microsatellite loci. Hardy–Weinberg equilibrium and allelic differentiation tests revealed that the fish from different sites significantly differed from a single panmictic and genetically uniform population, thus confirming the homing behaviour of the dace. The detection of a pattern of isolation by distance revealed that migration mostly occurred between nearby sites and decreased as distance from birth site increased. When considering the high population density of dace, their high swimming capability, the distribution of the spawning sites along the littoral zone, and the small size of the lake studied (<5 ha), these results strongly suggest natal site fidelity in this species. The detection of this phenomenon for this species is extremely useful for empirical investigations of factors affecting patterns of isolation by distance and of evolutionary perspectives of natal site fidelity in fishes.
Assessing the importance of macroinvertebrate trophic dead ends in the lower transfer of methylmercury in littoral food webs
Authors: Cremona Fabien , Planas Dolors , Lucotte Marc
Published: September 2008

Total mercury and methylmercury concentrations ([THg], [MeHg]) were measured in littoral macroinvertebrates from Lake St. Pierre, Quebec, Canada. Functional groups (detritivore, grazer, edible predator, inedible predator) explained the greatest fraction of [MeHg] variation compared with time (year, month), and space (station and shore). Greatest [THg] and [MeHg] were found in inedible predators mostly from families of heteropterans and coleopterans. Detritivores and grazers exhibited the lowest Hg concentrations, while edible predators were intermediate. Inedible predators also had the highest percentage of MeHg ([MeHg]/[THg]), with some taxa close to 100%. Such high percentages are seldom observed in freshwater organisms other than piscivorous fish. MeHg burden (concentrations × biomass) in inedible predators accounted for 10% of the MeHg pool for the whole invertebrate community. These large quantities of MeHg are sequestrated in aquatic “trophic dead ends” and could partly explain the low [MeHg] measured in fish, compared with [MeHg] of macroinvertebrates from Lake St. Pierre and other freshwater ecosystems with large littoral zones. We recommend taking into account the inedible organisms in Hg cycling models to avoid a possible overestimation of the MeHg pool available to fish.
Postconsumption domoic acid generation by the diatom Pseudo-nitzschia multiseries as a factor in depuration models
Authors: Stewart James E.
Published: September 2008

A theoretical analysis of the clearance of the neurotoxin domoic acid (DA) from molluscan shellfish, notably the blue mussel ( Mytilus edulis ), indicated that the depuration simulation did not account for the maximum accumulation of DA nor for the failure to eliminate all of the DA from the mussels in the anticipated time. Subsequent examination of relatively young, neurotoxin-producing cells of Pseudo-nitzschia multiseries concentrated 8.5- to 10-fold and reincubated in the dark, however, showed significant amounts of DA were produced within the first 24 h of incubation. The possible production of DA, after ingestion, could generate an additional contribution to the toxin burden in the mollusc, which, when included in the depuration simulation, would explain part or all of the observed disparity in the depuration experiment.
Improving gap light index (GLI) to quickly calculate gap coordinates
Authors: Hu Lile , Zhu Jiaojun
Published: September 2008

Understory light is essential to the establishment and growth of understory plants and varies temporally and spatially within gaps. The previously defined gap light index (GLI) is a good model for assessing understory light levels, but it is time-consuming to determine gap coordinates, which are crucial to GLI, for numerous points within a gap. This paper introduces the geometric calculation (GeoCalc) of gap coordinates. GeoCalc quickly obtains gap coordinates for any specified point within a canopy gap and takes into account the tridimensional profile of the gap and the slope and aspect of the ground. The GeoCalc-based GLI was validated by the GLI derived from hemispherical photographs taken at 93 sampling points within seven natural gaps. Our results demonstrate that GeoCalc-based GLI was strongly positively correlated and not significantly differed from the GLI derived from hemispherical photographs. Next, to analyze gap light regimes and the effects of gap size, canopy height, and topography, three natural gaps of various size were selected and simulated as nine gaps with 1 and 1.5 times canopy height or on the opposite slope. Finally, we have summarized characteristics of GeoCalc-based GLI and its application.
Tree-ring evidence extends the historic northern range limit of severe defoliation by insects in the aspen stands of western Quebec, Canada
Authors: Huang Jian-Guo , Tardif Jacques , Denneler Bernhard , Bergeron Yves , Berninger Frank
Published: September 2008

A dendrochronological reconstruction of insect outbreaks was conducted along a latitudinal gradient from 46°N to 54°N in the boreal forest of western Quebec, Canada. Tree-ring chronologies of the host species, trembling aspen ( Populus tremuloides Michx.), were constructed to identify periods of severe defoliation and comparisons were made with tree-ring chronologies of nonhost species. In addition, the frequency of white and narrow rings was used to further confirm the occurrence of insect outbreaks at these latitudes. Some major outbreaks occurred in relatively close synchrony at the regional scale, but the initiation year, intensity, and extent of the outbreaks varied spatially. For example, the 1950s outbreaks were observed from 1951 to 1952 at 46°N, from 1953 to 1954 at 47°N, and from 1954 to 1956 at 48°N. Other major outbreaks like the 1964 and 1980 outbreaks were fairly well synchronized at northern latitudes. The observed outbreaks in trembling aspen stands at 54°N also provided clear evidence that severe insect defoliation occurs much further north than the currently reported range limit, that is, between 49°N and 51°N, of the most important trembling aspen defoliator, the forest tent caterpillar ( Malacosoma disstria Hubner). Our study demonstrated that careful identification of white rings in host species can provide valid information allowing the expansion of the forestry insect inventory database both at temporal and spatial scales.
A relascope for measuring canopy cover
Authors: Stenberg Pauline , Korhonen Lauri , Rautiainen Miina
Published: September 2008

Angle count or relascope sampling has traditionally been used in forestry to estimate stand basal area. In this paper, we present an extension to the basal area relascope, the crown relascope, which differs from the normal relascope in that the relascope’s slot is very high and wide. We describe the theoretical basis of the instrument and present results from a field test in which a crown relascope with a basal area factor of 250 m2/ha (0.025) was used to estimate canopy cover of 73 sample plots in northern Finland. The crown relascope estimates had a root mean square difference of 9.3% and an average difference of –3.1% when compared with estimates obtained with the control method, line intersect sampling using the Cajanus tube. The results indicated that the crown relascope is a quick and fairly reliable instrument for canopy cover estimation, especially in relatively sparse forests where crown overlap is insignificant and visibility does not limit an efficient use of the instrument.
The effect of spacing on the growth ofEucalyptus camaldulensison salt-affected soils of the Punjab, Pakistan
Authors: Akhtar Javaid , Saqib Z. A. , Qureshi R. H. , Haq M. A. , Iqbal M. S. , Marcar N. E.
Published: September 2008

This study compared the performance of Eucalyptus camaldulensis Dehnh. planted at four spacings (2.0 m × 2.0 m, 2.5 m × 2.5 m, 3.0 m × 3.0 m, and 3.5 m × 3.5 m) at three experimental saline sites in Punjab province of Pakistan over 5 years and assessed the impact of these planting densities on soil salinity amelioration. Tree response was assessed by measuring survival, height, and diameter at breast height (DBH) of trees at 1, 2, and 5 years as well as wood volume after 5 years. Wood volume per hectare, height, and DBH were greater at sites I and II than at site III. The 3.0 m × 3.0 m spacing resulted in taller trees, but DBH and wood volume were greater with the 3.5 m × 3.5 m spacing. The study confirmed that initial tree spacing or density has a significant impact on the subsequent height, DBH, and wood volume of E. camaldulensis plants. The study also showed that broad spacing could be a better option in saline environments. There was a definite reduction in soil salinity (electrical conductivity, ECe) at five soil depths after 5 years of tree growth at all sites and spacing treatments, with reductions varying from 46% to 47% at site I, 31% to 52% at site II, and 25% to 58% at site III. Soil ECewas generally higher in surface (0–15 cm) soils.
Nutrient fluxes via leaching from coarse woody debris in a Fagus sylvatica forest in the Solling Mountains, Germany
Authors: Kuehne C. , Donath C. , Müller-Using S. I. , Bartsch N.
Published: September 2008

To evaluate the importance of nutrient fluxes via leaching from coarse woody debris (CWD) in an area with high atmospheric nitrogen (N) inputs, throughfall and CWD leachate from logs at different stages of decomposition were investigated over a period of 14 and 27 months, respectively, in a 160-year-old European beech ( Fagus sylvatica L.) forest in northwestern Germany. Water samples, collected from 30 zero-tension lysimeters installed in pairs along 15 logs and from 27 neighboring raingauges, were chemically analyzed in the laboratory. Generally, as CWD decay advanced, the ratio of leachate to throughfall decreased, and the amount of dissolved nutrients in the leachate increased. With the exception of ammonium (NH4+) and dissolved inorganic carbon, the element concentrations in the CWD leachate were significantly higher than those in the throughfall. The concentrations of NH4+and nitrate (NO3–) in the CWD leachate, which were very high compared with values from North American studies, were caused by the continuously high atmospheric N inputs, and the resulting N saturation in the forest ecosystem investigated. The low concentrations of the cations calcium and magnesium indicate that at this site nutrients limiting plant and fungal growth are retained and accumulated in the CWD.
Comparison of bandwidth selection in application of geographically weighted regression: a case study
Authors: Guo Luo , Ma Zhihai , Zhang Lianjun
Published: September 2008

A forest plot with a clustered spatial pattern of tree locations was used to investigate the impacts of different kernel functions (fixed vs. adaptive) and different sizes of bandwidth on model fitting, model performance, and spatial characteristics of the geographically weighted regression (GWR) coefficient estimates and model residuals. Our results indicated that (i) the GWR models with smaller bandwidths fit the data better, yielded smaller model residuals across tree sizes, significantly reduced spatial autocorrelation and heterogeneity for model residuals, and generated better spatial patterns for model residuals; however, smaller bandwidth sizes produced a high level of coefficient variability; (ii) the GWR models based on the fixed spatial kernel function produced smoother spatial distributions for the model coefficients than those based on the adaptive kernel function; and (iii) the GWR cross-validation or Akaike’s information criterion (AIC) optimization process may not produce an “optimal” bandwidth for model fitting and performance. It was evident that the selection of spatial kernel function and bandwidth has a strong impact on the descriptive and predictive power of GWR models.
Effects of fire intensity on survival and recovery of soil microarthropods after a clearcut burning
Authors: Malmström Anna , Persson Tryggve , Ahlström Kerstin
Published: September 2008

We studied responses of soil microarthropods to different burning intensities at a clearcut that was burnt in May 2002. Fire intensity was manipulated by adding or removing logging residues as fuel from the experimental plots. Samples were taken 1 week before and 1 week after burning as well as during autumn of the same year. Samples were taken in the 2 following years to estimate long-term recovery. No difference in humus combustion could be detected between burning intensities, but most microarthropod species showed lower abundances in the hard-burnt than in the light-burnt plots immediately after fire. Surface-living species also declined in light-burnt plots, whereas soil-living species were particularly affected in hard-burnt plots. This is probably explained by greater heat transfer into the hard-burnt soil. Total abundances of Oribatida and Protura remained low for several years in the burnt plots, whereas abundances of Collembola and Mesostigmata recovered within 1 year, which indicates that at least these groups had enough habitat space and food resources after fire. The study indicates that fire severity (depth of burn) is more decisive than fire intensity (heat release) for the long-term recovery of soil fauna, whereas fire intensity determines the acute survival of animals.
NUMERICAL TREATMENT OF A NONLINEAR NONLOCAL TRANSPORT EQUATION MODELING CRYSTAL PRECIPITATION
Authors: GOBBI ROMINA , PALPACELLI SILVIA , SPIGLER RENATO
Published: September 2008

Numerical methods to solve certain nonlinear nonlocal transport equations (hyperbolic partial differential equations with smooth solutions), even singular at the boundary, are developed and analyzed. As a typical case, a model equation used to describe certain crystal precipitation phenomena (a slight variant of the so-called Lifshitz–Slyozov–Wagner model) is considered. Choosing a train of few delta functions as initial crystal size distribution, one can model the technologically important case of having only a modest number of crystal sizes. This leads to the reduction of the transport equation to a system of ordinary differential equations, and suggests a new method of solution for the transport equation, based on Shannon sampling, which is widely used in communication theory.
ON THE INVISCID LIMIT OF A MODEL FOR CRACK PROPAGATION
Authors: KNEES DOROTHEE , MIELKE ALEXANDER , ZANINI CHIARA
Published: September 2008

We study the evolution of a single crack in an elastic body and assume that the crack path is known in advance. The motion of the crack tip is modeled as a rate-independent process on the basis of Griffith's local energy release rate criterion. According to this criterion, the system may stay in a local minimum before it performs a jump. The goal of this paper is to prove the existence of such an evolution and to shed light on the discrepancy between the local energy release rate criterion and models which are based on a global stability criterion (as for example the Francfort/Marigo model). We construct solutions to the local model via the vanishing viscosity method and compare different notions of weak, local and global solutions.
Cancer Screening: The Clash of Science and Intuition
Authors: Kramer Barnett S. , Croswell Jennifer Miller
Published: September 2008

The concept of early detection of cancer holds great promise and intuitive appeal. However, powerful biases can mislead clinicians when evaluating the efficacy of screening tests by clinical observation alone. Selection bias, lead-time bias, length-biased sampling, and overdiagnosis are counterintuitive concepts with critical implications for early-detection efforts. This article explains these biases and other common confounders in cancer screening. The most direct and reliable way to avoid being led astray by intuitions is through the use of randomized controlled trials.
Aldosterone regulation of intestinal Na absorption involves SGK-mediated changes in NHE3 and Na+pump activity
Authors: Musch Mark W. , Lucioni Alvaro , Chang Eugene B.
Published: September 2008

Aldosterone-induced intestinal Na+absorption is mediated by increased activities of apical membrane Na+/H+exchange (aNHE3) and basolateral membrane Na+-K+-ATPase (BLM-Na+-K+-ATPase) activities. Because the processes coordinating these events were not well understood, we investigated human intestinal Caco-2BBE cells where aldosterone increases within 2–4 h of aNHE3 and α-subunit of BLM-Na+-K+-ATPase, but not total abundance of these proteins. Although aldosterone activated Akt2 and serum glucorticoid kinase-1 (SGK-1), the latter through stimulation of phosphatidylinositol 3-kinase (PI3K), only the SGK-1 pathway mediated its effects on Na+-K+-ATPase. Ouabain inhibition of the early increase in aldosterone-induced Na+-K+-ATPase activation blocked most of the apical NHE3 insertion, possibly by inhibiting Na+-K+-ATPase-induced changes in intracellular sodium concentration ([Na]i). Over the next 6–48 h, further increases in aNHE3 and BLM-Na+-K+-ATPase activity and total protein expression were observed to be largely mediated by aldosterone-activated SGK-1 pathway. Aldosterone-induced increases in NHE3 mRNA, for instance, could be inhibited by RNA silencing of SGK-1, but not Akt2. Additionally, aldosterone-induced increases in NHE3 promoter activity were blocked by silencing SGK-1 as well as pharmacological inhibition of PI3K. In conclusion, aldosterone-stimulated intestinal Na+absorption involves two phases. The first phase involves stimulation of PI3K, which increases SGK-dependent insertion and function of BLM-Na+-K+-ATPase and subsequent increased membrane insertion of aNHE3. The latter may be caused by Na+-K+-ATPase-induced changes in [Na] or transcellular Na flux. The second phase involves SGK-dependent increases in total NHE3 and Na+-K+-ATPase protein expression and activities. The coordination of apical and BLM transporters after aldosterone stimulation is therefore a complex process that requires multiple time- and interdependent cellular processes.
Positive net movements of amino acids in the hindlimb after overnight food deprivation contribute to sustaining the elevated anabolism of neonatal pigs
Authors: Thivierge M. Carole , Bush Jill A. , Suryawan Agus , Nguyen Hanh V. , Orellana Renan A. , Burrin Douglas G. , Jahoor Farook , Davis Teresa A.
Published: September 2008

During the neonatal period, high protein breakdown rate is a metabolic process inherent to elevated rates of protein accretion in skeletal muscle. To determine the relationship between hindlimb net movements of essential and nonessential amino acids in the regulation of hindlimb protein breakdown during an overnight fasting-feeding cycle, we infused overnight-food-deprived 10- and 28-day-old piglets with [1-13C]phenylalanine and [ ring-2H4]tyrosine over 7 h (during 3 h of fasting and then during 4 h of feeding). Extraction rates for aspartate and glutamate after an overnight fast were 15% and 51% in the 10-day-old compared with 6% and 25% in the 28-day-old ( P < 0.05) piglets, suggesting an altered requirement for precursors of amino acids to shuttle nitrogen to the liver as early life progresses. This occurred simultaneously with marginal positive hindlimb net balance of essential amino acids after an overnight fast, with negative net release of many nonessential amino acids, such as alanine, asparagine, glutamine, glycine, and proline. This suggests that newborn muscle does not undergo significant protein mobilization after a short period of fasting in support of an elevated rate of protein accretion. Furthermore, tyrosine efflux from hindlimb breakdown between overnight fasting and feeding periods was not different in the 10-day-old piglets, for which tyrosine was limiting, but when tyrosine supply balanced requirements in the 28-day-old piglet, hindlimb efflux was increased ( P = 0.01). The results of the present study indicate that proteolysis and net movements of amino acids are coordinated mechanisms that sustain the elevated rate of net protein accretion during overnight feeding-fasting cycles in the neonate.
Common SNPs in HMGCR in Micronesians and Whites Associated With LDL-Cholesterol Levels Affect Alternative Splicing of Exon13
Authors: Burkhardt Ralph , Kenny Eimear E. , Lowe Jennifer K. , Birkeland Andrew , Josowitz Rebecca , Noel Martha , Salit Jacqueline , Maller Julian B. , Pe'er Itsik , Daly Mark J. , Altshuler David , Stoffel Markus , Friedman Jeffrey M. , Breslow Jan L.
Published: September 2008

Background—

Variation in LDL-cholesterol (LDL-C) among individuals is a complex genetic trait involving multiple genes and gene-environment interactions.

Methods and Results—

In a genome-wide association study (GWAS) to identify genetic variants influencing LDL-C in an isolated population from Kosrae, we observed associations for SNPs in the gene encoding 3hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase (HMGCR). Three of these SNPs (rs7703051, rs12654264, and rs3846663) met the statistical threshold of genome-wide significance when combined with data from the Diabetes Genetics Initiative GWAS. We followed up the association results and identified a functional SNP in intron13 (rs3846662), which was in linkage disequilibrium with the SNPs of genome-wide significance and affected alternative splicing of HMGCR mRNA. In vitro studies in human lymphoblastoid cells demonstrated that homozygosity for the rs3846662 minor allele was associated with up to 2.2-fold lower expression of alternatively spliced HMGCR mRNA lacking exon13, and minigene transfection assays confirmed that allele status at rs3846662 directly modulated alternative splicing of HMGCR exon13 (42.9±3.9 versus 63.7±1.0%Δexon13/total HMGCR mRNA,
P
=0.02). Further, the alternative splice variant could not restore HMGCR activity when expressed in HMGCR deficient UT-2 cells.

Conclusion—

We identified variants in HMGCR that are associated with LDL-C across populations and affect alternative splicing of HMGCR exon13.
Impaired Notch4 Activity Elicits Endothelial Cell Activation and Apoptosis
Authors: Quillard T. , Coupel S. , Coulon F. , Fitau J. , Chatelais M. , Cuturi M.C. , Chiffoleau E. , Charreau B.
Published: September 2008

Objective—

Notch signaling pathway controls key functions in vascular and endothelial cells (EC). However, little is known about the role of Notch in allografted vessels during the development of transplant arteriosclerosis (TA). This study investigated regulation of the Notch pathway on cardiac allograft arteriosclerosis and further examined its implication in EC dysfunction.

Methods and Results—

Here we show that, among Notch receptors, Notch2, -3, and -4 transcript levels were markedly downregulated in TA compared to tolerant and syngeneic allografts. TA correlates with high levels of tumor necrosis factor (TNF), transforming growth factor (TGF)β, and IL10, which consistently decrease Notch4 expression in transplants and cultured ECs. We found that inhibition of Notch activity, reflected by both a reduced CBF1 activity and Hes1 expression, parallels the downregulation of Notch4 expression mediated by TNF in ECs. Notch4 and Hes1 knockdown enhances vascular cell adhesion molecule-1 expression and promotes EC apoptosis. Silencing Notch4 or Hes1 also drastically inhibits repair of endothelial injury. Overall, our results suggest that Notch4 and basal Notch activity are required to maintain EC quiescence and for optimal survival and repair in response to injury.

Conclusion—

Together, our findings indicate that impaired Notch4 activity in graft ECs is a key event associated with TA by triggering EC activation and apoptosis.
Liver X Receptor Activation Induces the Uptake of Cholesteryl Esters From High Density Lipoproteins in Primary Human Macrophages
Authors: Bultel Stephanie , Helin Lionel , Clavey Veronique , Chinetti-Gbaguidi Giulia , Rigamonti Elena , Colin Morvane , Fruchart Jean-Charles , Staels Bart , Lestavel Sophie
Published: September 2008

Objective—

Liver X receptors (LXRs) are oxysterol-activated nuclear receptors regulating reverse cholesterol transport, in part by modulating cholesterol efflux from macrophages to apoAI and HDL via the ABCA1 and ABCG1/ABCG4 pathways. Moreover, LXR activation increases intracellular cholesterol trafficking via the induction of NPC1 and NPC2 expression. However, implication of LXRs in the selective uptake of cholesteryl esters from lipoproteins in human macrophages has never been reported.

Methods and Results—

Our results show that (1) selective CE uptake from HDL
3
is highly efficient in human monocyte-derived macrophages; (2) surprisingly, HDL
3
-CE uptake is strongly increased by LXR activation despite antiatherogenic effects of LXRs; (3) HDL
3
-CE uptake increase is not linked to SR-BI expression modulation but it is dependent of proteoglycan interactions; (4) HDL
3
-CE uptake increase is associated with increased expression and secretion of apoE and LPL, two proteins interacting with proteoglycans; (5) HDL
3
-CE uptake increase depends on the integrity of raft domains and is associated with an increased caveolin-1 expression.

Conclusions—

Our study identifies a new role for LXRs in the control of cholesterol homeostasis in human macrophages. LXR activation results in enhanced dynamic intracellular cholesterol fluxes through an increased CE uptake from HDL and leads to an increased cholesterol availability to efflux to apoAI and HDL.
Disruption of Sarcolemmal ATP-Sensitive Potassium Channel Activity Impairs the Cardiac Response to Systolic Overload
Authors: Hu Xinli , Xu Xin , Huang Yimin , Fassett John , Flagg Thomas P. , Zhang Ying , Nichols Colin G. , Bache Robert J. , Chen Yingjie
Published: September 2008

Sarcolemmal ATP-sensitive potassium channels (K
ATP
) act as metabolic sensors that facilitate adaptation of the left ventricle to changes in energy requirements. This study examined the mechanism by which K
ATP
dysfunction impairs the left ventricular response to stress using transgenic mouse strains with cardiac-specific disruption of K
ATP
activity (SUR1-tg mice) or Kir6.2 gene deficiency (Kir6.2 KO). Both SUR1-tg and Kir6.2 KO mice had normal left ventricular mass and function under unstressed conditions. Following chronic transverse aortic constriction, both SUR1-tg and Kir6.2 KO mice developed more severe left ventricular hypertrophy and dysfunction as compared with their corresponding WT controls. Both SUR1-tg and Kir6.2 KO mice had significantly decreased expression of peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and a group of energy metabolism related genes at both protein and mRNA levels. Furthermore, disruption of K
ATP
repressed expression and promoter activity of PGC-1α in cultured rat neonatal cardiac myocytes in response to hypoxia, indicating that K
ATP
activity is required to maintain PGC-1α expression under stress conditions. PGC-1α gene deficiency also exacerbated chronic transverse aortic constriction–induced ventricular hypertrophy and dysfunction, suggesting that depletion of PGC-1α can worsen systolic overload induced ventricular dysfunction. Both SUR1-tg and Kir6.2 KO mice had decreased FOXO1 after transverse aortic constriction, in agreement with the reports that a decrease of FOXO1 can repress PGC-1α expression. Furthermore, inhibition of K
ATP
caused a decrease of FOXO1 associated with PGC-1α promoter. These data indicate that K
ATP
channels facilitate the cardiac response to stress by regulating PGC-1α and its target genes, at least partially through the FOXO1 pathway.
Nuclear α1-Adrenergic Receptors Signal Activated ERK Localization to Caveolae in Adult Cardiac Myocytes
Authors: Wright Casey D. , Chen Quanhai , Baye Nichole L. , Huang Yuan , Healy Chastity L. , Kasinathan Sivakanthan , O'Connell Timothy D.
Published: September 2008

We previously identified an α1-AR-ERK (α1A-adrenergic receptor–extracellular signal-regulated kinase) survival signaling pathway in adult cardiac myocytes. Here, we investigated localization of α1-AR subtypes (α1A and α1B) and how their localization influences α1-AR signaling in cardiac myocytes. Using binding assays on myocyte subcellular fractions or a fluorescent α1-AR antagonist, we localized endogenous α1-ARs to the nucleus in wild-type adult cardiac myocytes. To clarify α1 subtype localization, we reconstituted α1 signaling in cultured α1A- and α1B-AR double knockout cardiac myocytes using α1-AR–green fluorescent protein (GFP) fusion proteins. Similar to endogenous α1-ARs and α1A- and α1B-GFP colocalized with LAP2 at the nuclear membrane. α1-AR nuclear localization was confirmed in vivo using α1-AR-GFP transgenic mice. The α1-signaling partners Gαq and phospholipase Cβ1 also colocalized with α1-ARs only at the nuclear membrane. Furthermore, we observed rapid catecholamine uptake mediated by norepinephrine-uptake-2 and found that α1-mediated activation of ERK was not inhibited by a membrane impermeant α1-blocker, suggesting α1 signaling is initiated at the nucleus. Contrary to prior studies, we did not observe α1-AR localization to caveolae, but we found that α1-AR signaling initiated at the nucleus led to activated ERK localized to caveolae. In summary, our results show that nuclear α1-ARs transduce signals to caveolae at the plasma membrane in cardiac myocytes.
Glycogen Synthase Kinase 3 Inhibition Slows Mitochondrial Adenine Nucleotide Transport and Regulates Voltage-Dependent Anion Channel Phosphorylation
Authors: Das Samarjit , Wong Renee , Rajapakse Nishadi , Murphy Elizabeth , Steenbergen Charles
Published: September 2008

Inhibition of glycogen synthase kinase (GSK)-3 reduces ischemia/reperfusion injury by mechanisms that involve the mitochondria. The goal of this study was to explore possible molecular targets and mechanistic basis of this cardioprotective effect. In perfused rat hearts, treatment with GSK inhibitors before ischemia significantly improved recovery of function. To assess the effect of GSK inhibitors on mitochondrial function under ischemic conditions, mitochondria were isolated from rat hearts perfused with GSK inhibitors and were treated with uncoupler or cyanide or were made anoxic. GSK inhibition slowed ATP consumption under these conditions, which could be attributable to inhibition of ATP entry into the mitochondria through the voltage-dependent anion channel (VDAC) and/or adenine nucleotide transporter (ANT) or to inhibition of the F
1
F
0
-ATPase. To determine the site of the inhibitory effect on ATP consumption, we measured the conversion of ADP to AMP by adenylate kinase located in the intermembrane space. This assay requires adenine nucleotide transport across the outer but not the inner mitochondrial membrane, and we found that GSK inhibitors slow AMP production similar to their effect on ATP consumption. This suggests that GSK inhibitors are acting on outer mitochondrial membrane transport. In sonicated mitochondria, GSK inhibition had no effect on ATP consumption or AMP production. In intact mitochondria, cyclosporin A had no effect, indicating that ATP consumption is not caused by opening of the mitochondrial permeability transition pore. Because GSK is a kinase, we assessed whether protein phosphorylation might be involved. Therefore, we performed Western blot and 1D/2D gel phosphorylation site analysis using phos-tag staining to indicate proteins that had decreased phosphorylation in hearts treated with GSK inhibitors. Liquid chromatographic–mass spectrometric analysis revealed 1 of these proteins to be VDAC2. Taken together, we found that GSK-mediated signaling modulates transport through the outer membrane of the mitochondria. Both proteomics and adenine nucleotide transport data suggest that GSK regulates VDAC and that VDAC may be an important regulatory site in ischemia/reperfusion injury.
Isoprostanes Inhibit Vascular Endothelial Growth Factor–Induced Endothelial Cell Migration, Tube Formation, and Cardiac Vessel Sprouting In Vitro, As Well As Angiogenesis In Vivo via Activation of the Thromboxane A
2
Receptor
Authors: Benndorf Ralf A. , Schwedhelm Edzard , Gnann Anke , Taheri Raihana , Kom Ghainsom , Didié Michael , Steenpass Anna , Ergün Süleyman , Böger Rainer H.
Published: September 2008

Isoprostanes are endogenously formed end products of lipid peroxidation. Furthermore, they are markers of oxidative stress and independent risk markers of coronary heart disease. In patients experiencing coronary heart disease, impaired angiogenesis may exacerbate insufficient blood supply of ischemic myocardium. We therefore hypothesized that isoprostanes may exert detrimental cardiovascular effects by inhibiting angiogenesis. We studied the effect of isoprostanes on vascular endothelial growth factor (VEGF)-induced migration and tube formation of human endothelial cells (ECs), and cardiac angiogenesis in vitro as well as on VEGF-induced angiogenesis in the chorioallantoic membrane assay in vivo. The isoprostanes 8-iso-PGF
2α
, 8-iso-PGE
2
, and 8-iso-PGA
2
inhibited VEGF-induced migration, tube formation of ECs, and cardiac angiogenesis in vitro, as well as VEGF-induced angiogenesis in vivo via activation of the thromboxane A
2
receptor (TBXA2R): the specific TBXA2R antagonists SQ-29548, BM 567, and ICI 192,605 but not the thromboxane A
2
synthase inhibitor ozagrel blocked the effect of isoprostanes. The isoprostane 8-iso-PGA
2
degraded into 2 biologically active derivatives in vitro, which also inhibited EC tube formation via the TBXA2R. Moreover, short hairpin RNA–mediated knockdown of the TBXA2R antagonized isoprostane-induced effects. In addition, Rho kinase inhibitor Y-27632 reversed the inhibitory effect of isoprostanes and the thromboxane A
2
mimetic U-46619 on EC migration and tube formation. Finally, the various isoprostanes exerted a synergistic inhibitory effect on EC tube formation. We demonstrate for the first time that isoprostanes inhibit angiogenesis via activation of the TBXA2R. By this mechanism, isoprostanes may contribute directly to exacerbation of coronary heart disease and to capillary rarefaction in disease states of increased oxidative stress.
Delay to Diagnosis in Acute Pediatric Arterial Ischemic Stroke
Authors: Rafay Mubeen F. , Pontigon Ann-Marie , Chiang Jackie , Adams Margaret , Jarvis D. Anna , Silver Frank , MacGregor Daune , deVeber Gabrielle A.
Published: September 2008

Background and Purpose—

For the clinician, the diagnosis of arterial ischemic stroke (AIS) in children is a challenge. Prompt diagnosis of pediatric AIS within 6 hours enables stroke-specific thrombolytic and neuroprotective strategies.

Methods—

We conducted a retrospective study of prospectively enrolled consecutive cohort of children with AIS, admitted to The Hospital for Sick Children, Toronto, from January 1992 to December 2004. The data on clinical presentation, symptom onset, emergency department arrival, neuroimaging and stroke diagnosis were recorded. The putative predictors of delayed diagnosis were selected a priori for analysis.

Results—

A total of 209 children with AIS were studied. The median interval from symptom onset to AIS diagnosis was 22.7 hours (interquartile range: 7.1 to 57.7 hours), prehospital delay (symptom onset to hospital arrival) was 1.7 hours (interquartile range: 49 minutes to 8.1 hours), and the in-hospital delay (presentation to diagnosis) was 12.7 hours (interquartile range: 4.5 to 33.5 hours). The initial assessment was completed in 16 minutes and initial neuroimaging in 8.8 hours. The diagnosis of AIS was suspected on initial assessment in 79 (38%) children and the initial neuroimaging diagnosed AIS in 47%. The parent’s help seeking action, nonabrupt onset of symptoms, altered consciousness, milder stroke severity, posterior circulation infarction and lack of initial neuroimaging at a tertiary hospital were predictive delayed AIS diagnosis.

Conclusion—

In the diagnosis of AIS, significant prehospital and in-hospital delays exist in children. Several predictors of the delayed AIS diagnosis were identified in the present study. Efforts to target these predictors can reduce diagnostic delays and optimize the management of AIS in children.
Another Note on Zeno's Arrow
Authors: Magidor Ofra
Published: September 2008

In Physics VI.9 Aristotle addresses Zeno's four paradoxes of motion and amongst them the arrow paradox. In his brief remarks on the paradox, Aristotle suggests what he takes to be a solution to the paradox.In two famous papers, both called 'A note on Zeno's arrow', Gregory Vlastos and Jonathan Lear each suggest an interpretation of Aristotle's proposed solution to the arrow paradox. In this paper, I argue that these two interpretations are unsatisfactory, and suggest an alternative interpretation. In particular, I claim that what seems on the face of it to be Aristotle's solution to the paradox raises two puzzles to which my interpretation, as opposed to Lear's and Vlastos's, provides an adequate response.