bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental factors affecting growth of eastern sand darter (Ammocrypta pellucida)
Authors: Drake D. A.R. , Power M. , Koops M. A. , Doka S. E. , Mandrak N. E.
Published: June 2008

Environmental factors affecting growth of the threatened eastern sand darter ( Ammocrypta pellucida (Putnam, 1863)) were examined using specimens sampled from the northern edge of its range to determine the species’ critical habitat. Length-at-age increments were determined from scale samples as surrogates for growth rates based on back-calculated lengths using the Fraser–Lee method. During the first year of life, 82% of total length is attained, suggesting considerable energetic partitioning towards reproduction following age-0. Positive relationships between age-0 length increments and sand substrates and between age-0 length increments and mean annual channel discharge indicated greatest first-year growth within sand-dominated, high-discharge habitats. Environmental factors that occurred at coarse spatial and temporal levels (i.e., mean annual channel discharge) explained more of the growth variability among eastern sand darters than those occurring at fine levels (i.e., site-level substrate composition). This study indicates that environmental factors can be used to explain variability in cohort-structured population and site-level growth of eastern sand darters.
Central-place foraging in nursing, arthropod-gleaning bats
Authors: Daniel Shai , Korine Carmi , Pinshow Berry
Published: June 2008

Central-place (CP) foraging theory predicts a positive correlation between the time a breeding CP forager spends in a patch and the distance of the patch to the CP. We found that nursing female Hemprich’s long-eared bats ( Otonycteris hemprichii Peters, 1859; Vespertilionidae) that forage around a lake in the Negev roost in only two areas: one 0.5–2 km (near) and one 9 km (far) from the foraging area. If these bats are CP foragers, then the strategies of the two groups should differ. We predicted that females roosting farther away would have longer but fewer foraging bouts. Using radiotelemetry, we measured the activity of six females from the near site and three from the far site. Without exception, females from the far site made a single, prolonged foraging bout each night, while females roosting nearby made several shorter bouts. Among the females from the near site, daily foraging time, mean daily foraging bout length, and first daily foraging bout length were all significantly and positively correlated with distance between the roost and the foraging site. Our data support the prediction that female O. hemprichii are CP foragers. We suggest that the females trade off using a safe roost site, distant from a choice foraging area, and lower nursing frequency against using a risky roost site close to the foraging area and greater nursing frequency.
Genetic characterization of Kenai brown bears (Ursus arctos): microsatellite and mitochondrial DNA control region variation in brown bears of the Kenai Peninsula, south central Alaska
Authors: Jackson J. V. , Talbot S. L. , Farley S.
Published: June 2008

We collected data from 20 biparentally inherited microsatellite loci, and nucleotide sequence from the maternally inherited mitochondrial DNA (mtDNA) control region, to determine levels of genetic variation of the brown bears ( Ursus arctos L., 1758) of the Kenai Peninsula, south central Alaska. Nuclear genetic variation was similar to that observed in other Alaskan peninsular populations. We detected no significant inbreeding and found no evidence of population substructuring on the Kenai Peninsula. We observed a genetic signature of a bottleneck under the infinite alleles model (IAM), but not under the stepwise mutation model (SMM) or the two-phase model (TPM) of microsatellite mutation. Kenai brown bears have lower levels of mtDNA haplotypic diversity relative to most other brown bear populations in Alaska.
Beyond mtDNA: nuclear gene flow suggests taxonomic oversplitting in the little brown bat (Myotis lucifugus)
Authors: Lausen C. L. , Delisle I. , Barclay R. M.R. , Strobeck C.
Published: June 2008

In southern Alberta and north-central Montana, there is substantial mtDNA sequence divergence between two groups of the little brown bat, Myotis lucifugus (LeConte, 1831), previously thought to be subspecies ( Myotis lucifugus lucifugus and Myotis lucifugus carissima ) but recently hypothesized to be species. We tested this hypothesis using population genetic techniques. Using nuclear microsatellite markers (10 loci), we found a lack of differentiation between these two groups of bats (ascribed based on mitochondrial hypervariable region II sequence), suggesting interbreeding was sympatric. Our findings add to the recent discovery that M. l. lucifugus haplotypes are found throughout the range previously thought to be only M. l. carissima, suggesting widespread sympatry and extensively mixed gene pools, thus refuting the cryptic species hypothesis. Clinal morphology and individual variation demonstrated the impossibility to differentiate groups based on original subspecies definitions. The lack of geographic and morphological boundaries, in addition to the likelihood that the interbreeding observed in this study is occurring across western North America, suggests that no line can be drawn between these two groups. We thus suggest that the carissima subspecies designation be dropped. This study highlights the importance of investigating nuclear gene flow in widely sympatric animals suspected of being cryptic genetic species, and has important implications for applications of the DNA Barcoding Project.
Feeding ecology of the Great Basin Rattlesnake (Crotalus lutosus, Viperidae)
Authors: Glaudas Xavier , Jezkova Tereza , Rodríguez-Robles Javier A.
Published: June 2008

Documenting variation in organismal traits is essential to understanding the ecology of natural populations. We relied on stomach contents of preserved specimens and literature records to assess ontogenetic, intersexual, temporal, and geographic variations in the feeding ecology of the North American Great Basin Rattlesnake ( Crotalus lutosus Klauber, 1930). Snakes preyed mainly on rodents, occasionally on lizards, and less frequently on birds; squamate eggs and frogs were rarely eaten. There was a positive relationship between predator and prey size. The best predictors of this relationship were prey diameter as a function of snake body length and head size, underscoring the importance of prey diameter for gape-limited predators such as snakes. Crotalus lutosus displayed ontogenetic, sexual, and seasonal variations in diet. Smaller rattlesnakes fed predominantly on lizards, whereas larger individuals mostly fed on mammals. Females fed on lizards more often than males. The proportion of mammals in the diet was highest during the summer, a temporal variation that may be related to behavioral shifts in the diel activity and prey selectivity of C. lutosus, and (or) to differential abundance of rodents between seasons. Great Basin Rattlesnakes also displayed geographic variation in feeding habits, with snakes from the Great Basin Desert eating a higher proportion of lizards than serpents from the more northern Columbia Plateau.
Habitat-patch occupancy in the common goldeneye (Bucephala clangula) at different stages of the breeding cycle: implications to ecological processes in patchy environments
Authors: Paasivaara Antti , Pöysä Hannu
Published: June 2008

We studied the pattern of habitat-patch occupancy of radio-tagged common goldeneye ( Bucephala clangula (L., 1758)) females in two sequential stages of the breeding season, the nest stage and the brood stage, and whether the resources needed in nesting and brood-rearing are spatially inter-related as revealed by patch occupation rate of goldeneye females in these stages. We also studied patch-specific factors potentially explaining the rate of patch occupation separately during the nest stage and the brood stage. There was no association in patch occupation rate between the nest stage and the brood stage, indicating that all the critical resources needed to complete a successful breeding cycle were not met within the same habitat patch. At the nest stage, patch occupation rate increased with nest-site availability and decreased with nest predation rate but was not affected by vegetation luxuriance or patch size. Vegetation luxuriance had a positive effect on patch occupation rate at the brood stage, whereas nesting success of the focal patch had no effect. Results suggest that nest-site selection and brood-stage habitat selection are governed by different ecological factors. We conclude that breeding-stage-specific resource requirements redistributed individuals among habitat patches across the landscape, implying dynamic distribution of ducks between nesting and brooding stage.
IN VITROACOUSTIC WAVE PROPAGATION IN HUMAN AND BOVINE CANCELLOUS BONE AS PREDICTED BY BIOT'S THEORY
Authors: CARDOSO LUIS , MEUNIER ALAIN , ODDOU CHRISTIAN
Published: June 2008

Recent in vitro studies have provided evidence of the propagation of two different longitudinal wave modes at ultrasonic frequencies in cancellous bone. The genesis of these two plane waves in fluid-saturated porous media is predicted by the poroelastic approach to wave propagation originally developed by Biot. However, wave velocity is usually analyzed as a function of bone mass density only; therefore, the influence of the cancellous bone microstructure over the wave velocity is not taken into account. In the present study, a descriptor of the microstructure is considered in Biot's theory. This model is used to evaluate the large experimental variability of both fast and slow wave velocities measured on randomly oriented human and bovine cancellous bone samples. The role of the anisotropic solid structure and fluid in the behavior of fast and slow wave velocities is examined. Experimental and theoretically predicted velocities are found in close agreement when analyzed as a function of both porosity and structural index. This model has the potential to be used to determine an acoustically derived structural index in cancellous bone.
APPLICATION OF BIOMECHANICS TO TISSUE ENGINEERING: A PERSONAL VIEW
Authors: MILTHORPE BRUCE K.
Published: June 2008

Cellular biomechanics is an area of study that is receiving more attention as time progresses. The response of cells to their mechanical environment, including biomechanical stimuli, has far-reaching ramifications for the area of tissue engineering, especially for tissues designed to withstand mechanical loading (e.g. bone, cartilage, tendons and ligaments, and arteries). The effects of mechanical stimuli on cells are only recently being examined, and the potential role of mechanical stimuli in tissue engineering is still one that is largely ignored in the design of tissue engineering scaffolds. The relationship of mechanical properties of scaffolds or of mechanical stimuli to cell behavior is complex, but vital to the development of the field. Also, understanding the complex interplay of form and environment on cells involves an increase in our knowledge of how cells react to their total environment including mechanical stimuli and material properties. In order to improve tissue engineering outcomes, a nexus must be developed between the mechanical, biochemical, and biological studies of cellular behavior, in the context of extremely complex systems.
THEORETICAL ANALYSIS OF BLOOD FLOW THROUGH AN ARTERIAL SEGMENT HAVING MULTIPLE STENOSES
Authors: MISRA J. C. , SINHA A. , SHIT G. C.
Published: June 2008

The present paper is concerned with the study of a mathematical model for the flow of blood through a multi-stenosed artery. Blood is considered here to consist of a peripheral plasma layer which is free from red cells, and a core region which is represented by a Casson fluid. A suitable generalized geometry of multiple stenoses existing in the arterial segment under consideration is taken for the study. A thorough quantitative analysis has been made through numerical computations of the variables involved in the analysis that are of special interest in the study. The computational results are presented graphically.
LOCALIZATION AND IMAGE QUALITY OF SPIRAL GOLD MARKERS USING DIFFERENT X-RAY IMAGING MODALITIES IN RADIATION THERAPY
Authors: ODERO D. O. , HARTLEY J. R. , SHIMM D. S.
Published: June 2008

It is important to deliver radiation to treatment targets with accuracy. Typically, patients are positioned using marks on the surface of the skin. However, without imaging procedures, there is no information about the location of mobile internal organs and targets. The use of implanted radiopaque markers can help localize internal target organs using imaging modalities. Quality assurance procedures have been performed on commercially available spiral gold markers to determine their location and image quality. The results obtained from different, least essential imaging modalities employed in radiation therapy showed that these markers are not as clearly visible on radiographs as compared to the modalities with electronic output formats. The image quality was also poorer on megavoltage as compared to kilovoltage X-ray imaging modalities.
A NOTE ON THE GENERAL RELATIONSHIP BETWEEN D-DIFFERENTIATION AND COVARIANT DIFFERENTIATION
Authors: HURLEY D. J. , VANDYCK M. A.
Published: June 2008

The most general operator of D-differentiation is proved to be expressible as a combination of covariant differentiation and a tensor field. The torsion, the curvature and the non-metricity of an arbitrary D-operator are consequently given in terms of those of covariant differentiation. The scalar curvature is also obtained.
PIROGOV–SINAI THEORY WITH NEW CONTOURS FOR SYMMETRIC MODELS
Authors: GANIKHODJAEV N. N. , ROZIKOV U. A.
Published: June 2008

The contour argument was introduced by Peierls for two dimensional Ising model. Peierls benefited from the particular symmetries of the Ising model. For non-symmetric models the argument was developed by Pirogov and Sinai. It is very general and rather difficult. Intuitively clear that the Peierls argument does work for any symmetric model. But contours defined in Pirogov–Sinai theory do not work if one wants to use Peierls argument for more general symmetric models. We give a new definition of contour which allows relatively easier proof to the main result of the Pirogov–Sinai theory for symmetric models. Namely, our contours allow us to apply the classical Peierls argument (with contour removal operation).
NEGATIVE FORMS AND PATH SPACE FORMS
Authors: CHATTERJEE SAIKAT , LAHIRI AMITABHA , SENGUPTA AMBAR N.
Published: June 2008

We present an account of negative differential forms within a natural algebraic framework of differential graded algebras, and explain their relationship with forms on path spaces.
LOCAL COHOMOLOGY AND THE VARIATIONAL BICOMPLEX
Authors: FERREIRO PÉREZ ROBERTO
Published: June 2008

The differential forms on the jet bundle J∞E of a bundle E → M over a compact n-manifold M of degree greater than n determine differential forms on the space Γ(E) of sections of E. The forms obtained in this way are called local forms on Γ(E), and its cohomology is called the local cohomology of Γ(E). More generally, if a group [Formula: see text] acts on E, we can define the local [Formula: see text]-invariant cohomology. The local cohomology is computed in terms of the cohomology of the jet bundle by means of the variational bicomplex theory. A similar result is obtained for the local [Formula: see text]-invariant cohomology. Using these results and the techniques for the computation of the cohomology of invariant variational bicomplexes in terms of relative Gelfand–Fuchs cohomology introduced in [4], we construct non trivial local cohomology classes in the important cases of Riemannian metrics with the action of diffeomorphisms, and connections on a principal bundle with the action of automorphisms.
TIME MACHINE AT THE LHC
Authors: AREF'EVA I. YA. , VOLOVICH I. V.
Published: June 2008

Recently, black hole and brane production at CERN's Large Hadron Collider (LHC) has been widely discussed. We suggest that there is a possibility to test causality at the LHC. We argue that if the scale of quantum gravity is of the order of few TeVs, proton-proton collisions at the LHC could lead to the formation of time machines (spacetime regions with closed timelike curves) which violate causality. One model for the time machine is a traversable wormhole. We argue that the traversable wormhole production cross section at the LHC is of the same order as the cross section for the black hole production. Traversable wormholes assume violation of the null energy condition (NEC) and an exotic matter similar to the dark energy is required. Decay of the wormholes/time machines and signatures of time machine events at the LHC are discussed.
History of RIGS in Wales: an example of successful cooperation for geoconservation
Authors: Burek Cynthia V.
Published: June 2008

The history of RIGS in Wales is an example of a rise, fall and rise again of a voluntary sector organization operating within the field of geoconservation. The Welsh RIGS movement began as small individual groups, which then gave rise to a national organization with specific needs and problems. As RIGS started in Wales before devolution in 1999, it was regarded as a regional grouping but after devolution it was well placed to take the national Welsh agenda of geoconservation forward. This paper explores the development of this co-operation through national conferences, the development of the Association of Welsh RIGS Groups and looks at the unique position that Wales holds within the field of geoconservation. Finally, the achievements of this approach are highlighted.
A vision of ‘deep time’: the ‘Geological Illustrations’ of Crystal Palace Park, London
Authors: Doyle Peter
Published: June 2008

Crystal Palace Park in the London Borough of Bromley is a masterpiece of park design by the visionary Sir Joseph Paxton. Created to house the iron and glass ‘Crystal Palace’ (the temporary structure built for the 1851 Great Exhibition in Hyde Park), the park was developed on a series of themed terraces, with the palace itself at the top of Sydenham Hill. The terraces were linked by a grand central walkway, and massive fountains played in gigantic fountain bowls. Today, the palace is gone, destroyed by fire in 1936; the fountains are quiet and their bowls occupied by the stadia of the National Sports Centre; and the central walk is interrupted by intrusive twentieth century concrete architecture. But one jewel of the original remains. In the SE corner lies a remnant of Paxton's original English landscape garden, a fragment populated with ‘antediluvian monsters’ and geological cliffs. This remnant is arguably the world's first attempt at recreating, in a systematic, scientific and ordered way, the geology of the United Kingdom, and its survival and subsequent restoration in 2001 is a remarkable testimony to its constructors and originators.

This paper examines the background and achievement of this first accurate recreation of geology in a public park, a Victorian monument to the relevance of promoting awareness of the science as a foundation to effective geoconservation.
Geological site designation under the 1972 UNESCO World Heritage Convention
Authors: Boylan Patrick J.
Published: June 2008

The World Heritage Convention, 1972, which aims to promote and support the conservation of the world's cultural and natural heritage, can be considered one of the world's most successful international treaties as it has been adopted by 184 states. However, for very many states it is primarily a way in which places that they consider to be their most important heritage sites and monuments can gain additional international recognition through inscription on the World Heritage List. Though geological interest is one of the major criteria for inscription on the World Heritage List, in practice relatively few sites have been inscribed wholly or partly because of their geological or geomorphological importance, (just 72 out of the current 851 World Heritage sites). Further, the present list of geological inscriptions is very uneven and unrepresentative of geological periods and Earth processes, and localities of key significance in the history of geology are almost absent. One weakness is that, although there is some professional geological advice through the World Conservation Union (one of the two official advisory bodies to the World Heritage Committee) there is no mechanism through which international geological science or history of geology organizations can contribute to the development of world heritage policies and the evaluation of nominations to the World Heritage List. However, the greatest problem is that most countries are not evaluating and nominating their national geological heritage. The geological community needs to become much more active in promoting geological conservation and nominations to the World Heritage Committee at the national level.
Towards a history of geotourism: definitions, antecedents and the future
Authors: Hose Thomas A.
Published: June 2008

Geotourism is a relatively new form of tourism with considerable growth potential. Initially researched and defined within the UK, it is a growing field of international academic study. The term passed into general usage in the early 1990s, although its antecedents date back to the seventeenth century. Its resource base includes geosites, museum, library and archive collections and artistic outputs. It has significant social history and industrial archaeology underpinnings. Relatively recently defined, and benefiting from a new appreciation of its historical roots and various outcomes, the concept is already undergoing redefinition and refinement. However, because of an inadequately developed historical perspective and theoretical framework, the rationale for its provision and the societal significance of its resource base is not always fully appreciated by existing and potential stakeholders. This account presents geotourism's historical and theoretical development, especially in Britain from which examples are drawn, and explores its likely future.
The role of the voluntary sector in the evolving geoconservation movement
Authors: Burek Cynthia V.
Published: June 2008

The role of the voluntary sector in geoconservation has a long history. However, its involvement in biodiversity conservation is even longer. A contrast is made between the biodiversity and geodiversity voluntary sectors through time. With the start of the movement arguably by the National Trust in the late nineteenth century, the baton (or hammer) has been taken up by geological societies locally and nationally, by individuals and more recently by the RIGS initiative. The word voluntary in no way diminishes the work undertaken and achieved by these people. It can be argued that without them geoconservation would not exist. This paper explores their contribution using case studies: National Trust and UKRIGS as national organizations, the RIGS movement as a local initiative, the Chester Society of Natural Science as ‘local’ interest and the work of individuals through time. The latest Local Geodiversity Action Plans (LGAPs) development as a recent historical phenomenon is explored and the importance of
local
as context for geoconservation illustrated.
The Geologists' Association and geoconservation: history and achievements
Authors: Green C. P.
Published: June 2008

The vulnerability of the geological record and of the natural environment in general was recognized in the nineteenth century. The Geologists' Association (GA) contributed to the national debate after the First World War and was active in consultations leading to the development of conservation policy and legislation in the 1940s. The geological issues attracted less attention in the 1950s and 1960s, but in the years that followed the GA became increasingly involved in conservation initiatives. The Fieldwork Code was published, the Curry Fund established and the GA became active in supplying the geological input to a wide variety of environmental conservation campaigns.
Disulfide-Linked Protein Folding Pathways
Authors: Mamathambika Bharath S. , Bardwell James C.
Published: June 2008

Determining the mechanism by which proteins attain their native structure is an important but difficult problem in basic biology. The study of protein folding is difficult because it involves the identification and characterization of folding intermediates that are only very transiently present. Disulfide bond formation is thermodynamically linked to protein folding. The availability of thiol trapping reagents and the relatively slow kinetics of disulfide bond formation have facilitated the isolation, purification, and characterization of disulfide-linked folding intermediates. As a result, the folding pathways of several disulfide-rich proteins are among the best known of any protein. This review discusses disulfide bond formation and its relationship to protein folding in vitro and in vivo.
Regulation of Spermatogonial Stem Cell Self-Renewal in Mammals
Authors: Oatley Jon M. , Brinster Ralph L.
Published: June 2008

Mammalian spermatogenesis is a classic adult stem cell–dependent process, supported by self-renewal and differentiation of spermatogonial stem cells (SSCs). Studying SSCs provides a model to better understand adult stem cell biology, and deciphering the mechanisms that control SSC functions may lead to treatment of male infertility and an understanding of the etiology of testicular germ cell tumor formation. Self-renewal of rodent SSCs is greatly influenced by the niche factor glial cell line–derived neurotrophic factor (GDNF). In mouse SSCs, GDNF activation upregulates expression of the transcription factor–encoding genes bcl6b, etv5, and lhx1, which influence SSC self-renewal. Additionally, the non-GDNF-stimulated transcription factors Plzf and Taf4b have been implicated in regulating SSC functions. Together, these molecules are part of a robust gene network controlling SSC fate decisions that may parallel the regulatory networks in other adult stem cell populations.
Hepatocyte nuclear factor-1α regulates glucocorticoid receptor expression to control postnatal body growth
Authors: Lin Wan-Yi , Hu Yu-Jie , Lee Ying-Hue
Published: June 2008

Hepatocyte nuclear factor 1α (HNF-1α) is a homeodomain-containing transcription factor and is important in postnatal growth and development in mice. In the HNF-1α-deficient liver, the expressions of a large set of growth hormone (GH)-responsive genes were significantly downregulated. By analyzing various HNF-1α mutant mice, we disclosed a mechanism by which hepatic HNF-1α regulates the expression of GH-responsive genes that are crucial for growth and development. We found that HNF-1α is required for the normal expression of glucocorticoid receptor (GR) specifically in livers. In the liver, GR, together with STAT5, is known to mediate the GH action by transactivating the GH-responsive genes that function in body growth and development. We further demonstrated that HNF-1α modulated GR gene expression by directly transactivating the GR gene promoter via a cryptic regulatory element located 3 bp upstream of the translation start site in exon 2 of the GR gene locus.
A murine model of obesity implicates the adipokine milieu in the pathogenesis of severe acute pancreatitis
Authors: Zyromski Nicholas J. , Mathur Abhishek , Pitt Henry A. , Lu Debao , Gripe John T. , Walker Julia J. , Yancey Kyle , Wade Terence E. , Swartz-Basile Deborah A.
Published: June 2008

Obesity is clearly an independent risk factor for increased severity of acute pancreatitis (AP), although the mechanisms underlying this association are unknown. Adipokines (including leptin and adiponectin) are pleiotropic molecules produced by adipocytes that are important regulators of the inflammatory response. We hypothesized that the altered adipokine milieu observed in obesity contributes to the increased severity of pancreatitis. Lean (C57BL/6J), obese leptin-deficient (LepOb), and obese hyperleptinemic (LepDb) mice were subjected to AP by six hourly intraperitoneal injections of cerulein (50 μg/kg). Severity of AP was assessed by histology and by measuring pancreatic concentration of the proinflammatory cytokines IL-1β and IL-6, the chemokine MCP-1, and the marker of neutrophil activation MPO. Both congenitally obese strains of mice developed significantly more severe AP than wild-type lean animals. Severity of AP was not solely related to adipose tissue volume: LepObmice were heaviest; however, LepDbmice developed the most severe AP both histologically and biochemically. Circulating adiponectin concentrations inversely mirrored the severity of pancreatitis. These data demonstrate that congenitally obese mice develop more severe AP than lean animals when challenged by cerulein hyperstimulation and suggest that alteration of the adipokine milieu exacerbates the severity of AP in obesity.
Necrotic core thickness and positive arterial remodeling index: emergent biomechanical factors for evaluating the risk of plaque rupture
Authors: Ohayon Jacques , Finet Gérard , Gharib Ahmed M. , Herzka Daniel A. , Tracqui Philippe , Heroux Julie , Rioufol Gilles , Kotys Melanie S. , Elagha Abdalla , Pettigrew Roderic I.
Published: June 2008

Fibrous cap thickness is often considered as diagnostic of the degree of plaque instability. Necrotic core area (Corearea) and the arterial remodeling index (Remodindex), on the other hand, are difficult to use as clinical morphological indexes: literature data show a wide dispersion of Corearea thresholds above which plaque becomes unstable. Although histopathology shows a strong correlation between Corearea and Remodindex, it remains unclear how these interact and affect peak cap stress (Capstress), a known predictor of rupture. The aim of this study was to investigate the change in plaque vulnerability as a function of necrotic core size and plaque morphology. Capstress value was calculated on 5,500 idealized atherosclerotic vessel models that had the original feature of mimicking the positive arterial remodeling process described by Glagov. Twenty-four nonruptured plaques acquired by intravascular ultrasound on patients were used to test the performance of the associated idealized morphological models. Taking advantage of the extensive simulations, we investigated the effects of anatomical plaque features on Capstress. It was found that: 1) at the early stages of positive remodeling, lesions were more prone to rupture, which could explain the progression and growth of clinically silent plaques and 2) in addition to cap thickness, necrotic core thickness, rather than area, was critical in determining plaque stability. This study demonstrates that plaque instability is to be viewed not as a consequence of fibrous cap thickness alone but rather as a combination of cap thickness, necrotic core thickness, and the arterial remodeling index.
Regulation of myocardin factor protein stability by the LIM-only protein FHL2
Authors: Hinson Jeremiah S. , Medlin Matt D. , Taylor Joan M. , Mack Christopher P.
Published: June 2008

Extensive evidence indicates that serum response factor (SRF) regulates muscle-specific gene expression and that myocardin family SRF cofactors are critical for smooth muscle cell differentiation. In a yeast two hybrid screen for novel SRF binding partners expressed in aortic SMC, we identified four and a half LIM domain protein 2 (FHL2) and confirmed this interaction by GST pull-down and coimmunoprecipitation assays. FHL2 also interacted with all three myocardin factors and enhanced myocardin and myocardin-related transcription factor (MRTF)-A-dependent transactivation of smooth muscle α-actin, SM22, and cardiac atrial natriuretic factor promoters in 10T1/2 cells. The expression of FHL2 increased myocardin and MRTF-A protein levels, and, importantly, this effect was due to an increase in protein stability not due to an increase in myocardin factor mRNA expression. Treatment of cells with proteasome inhibitors MG-132 and lactacystin strongly upregulated endogenous MRTF-A protein levels and resulted in a substantial increase in ubiquitin immunoreactivity in MRTF-A immunoprecipitants. Interestingly, the expression of FHL2 attenuated the effects of RhoA and MRTF-B on promoter activity, perhaps through decreased MRTF-B nuclear localization or decreased SRF-CArG binding. Taken together, these data indicate that myocardin factors are regulated by proteasome-mediated degradation and that FHL2 regulates SRF-dependent transcription by multiple mechanisms, including stabilization of myocardin and MRTF-A.
Endurance capacity in maturing mdx mice is markedly enhanced by combined voluntary wheel running and green tea extract
Authors: Call Jarrod A. , Voelker Kevin A. , Wolff Andrew V. , McMillan Ryan P. , Evans Nick P. , Hulver Matthew W. , Talmadge Robert J. , Grange Robert W.
Published: June 2008

Duchenne muscular dystrophy is characterized by the absence of dystrophin from muscle cells. Dystrophic muscle cells are susceptible to oxidative stress. We tested the hypothesis that 3 wk of endurance exercise starting at age 21 days in young male mdx mice would blunt oxidative stress and improve dystrophic skeletal muscle function, and these effects would be enhanced by the antioxidant green tea extract (GTE). In mice fed normal diet, average daily running distance increased 300% from week 1 to week 3, and total distance over 3 wk was improved by 128% in mice fed GTE. Running, independent of diet, increased serum antioxidant capacity, extensor digitorum longus tetanic stress, and total contractile protein content, heart citrate synthase, and heart and quadriceps β-hydroxyacyl-CoA dehydrogenase activities. GTE, independent of running, decreased serum creatine kinase and heart and gastrocnemius lipid peroxidation and increased gastrocnemius citrate synthase activity. These data suggest that both endurance exercise and GTE may be beneficial as therapeutic strategies to improve muscle function in mdx mice.
Exercise training initiated after the onset of diabetes preserves myocardial function: effects on expression of β-adrenoceptors
Authors: Bidasee Keshore R. , Zheng Hong , Shao Chun-Hong , Parbhu Sheeva K. , Rozanski George J. , Patel Kaushik P.
Published: June 2008

The present study was undertaken to assess cardiac function and characterize β-adrenoceptor subtypes in hearts of diabetic rats that underwent exercise training (ExT) after the onset of diabetes. Type 1 diabetes was induced in male Sprague-Dawley rats using streptozotocin. Four weeks after induction, rats were randomly divided into two groups. One group was exercised trained for 3 wk while the other group remained sedentary. At the end of the protocol, cardiac parameters were assessed using M-mode echocardiography. A Millar catheter was also used to assess left ventricular hemodynamics with and without isoproterenol stimulation. β-Adrenoceptors were assessed using Western blots and [3H]dihydroalprenolol binding. After 7 wk of diabetes, heart rate decreased by 21%, fractional shortening by 20%, ejection fraction by 9%, and basal and isoproterenol-induced dP/d t by 35%. β1- and β2-adrenoceptor proteins were reduced by 60% and 40%, respectively, while β3-adrenoceptor protein increased by 125%. Ventricular homogenates from diabetic rats bound 52% less [3H]dihydroalprenolol, consistent with reductions in β1- and β2-adrenoceptors. Three weeks of ExT initiated 4 wk after the onset of diabetes minimized cardiac function loss. ExT also blunted loss of β1-adrenoceptor expression. Interestingly, ExT did not prevent diabetes-induced reduction in β2-adrenoceptor or the increase of β3-adrenoceptor expression. ExT also increased [3H]dihydroalprenolol binding, consistent with increased β1-adrenoceptor expression. These findings demonstrate for the first time that ExT initiated after the onset of diabetes blunts primarily β1-adrenoceptor expression loss, providing mechanistic insights for exercise-induced improvements in cardiac function.
Airway constriction measured from tantalum bronchograms in conscious mice in response to methacholine
Authors: Lai-Fook Stephen J. , Houtz Pamela K.
Published: June 2008

A single-projection X-ray technique showed an increase in functional residual capacity (FRC) in conscious mice in response to aerosolized methacholine (MCh) with little change in airway resistance (Raw) measured using barometric plethysmography (Lai-Fook SJ, Houtz PK, Lai Y-L. J Appl Physiol 104: 521–533, 2008). The increase in FRC presumably prevented airway constriction by offsetting airway contractility. We sought a more direct measure of airway constriction. Anesthetized Balb/c mice were intubated with a 22-G catheter, and tantalum dust was insufflated into the lungs to produce a well-defined bronchogram. After overnight recovery, the conscious mouse was placed in a sealed box, and bronchograms were taken at maximum and minimum points of the box pressure cycle before (control) and after 1-min exposures to 25, 50, and 100 mg/ml MCh aerosol. After overnight recovery, each mouse was studied under both room and body temperature box air conditions to correct for gas compression effects on the control tidal volume (Vt) and to determine Vt and Raw with MCh. Airway diameter ( D), FRC, and Vt were measured from the X-ray images. Compared with control, D decreased by 24%, frequency decreased by 35%, FRC increased by 120%, and Raw doubled, to reach limiting values with 100 mg/ml MCh. Vt was unchanged with MCh. The limiting D occurred near zero airway elastic recoil, where the maximal contractility was relatively small. The conscious mouse adapted to MCh by breathing at a higher lung volume and reduced frequency to reach a limit in constriction.
Glycogen Synthase Kinase-3 Inactivation Is Not Required for Ischemic Preconditioning or Postconditioning in the Mouse
Authors: Nishino Yasuhiro , Webb Ian G. , Davidson Sean M. , Ahmed Aminul I. , Clark James E. , Jacquet Sebastien , Shah Ajay M. , Miura Tetsuji , Yellon Derek M. , Avkiran Metin , Marber Michael S.
Published: June 2008

The inactivation of glycogen synthase kinase-3β (GSK-3β) is proposed as the event integrating protective pathways initiated by preconditioning and other interventions. The inactivation of GSK-3 is thought to decrease the probability of opening of the mitochondrial permeability transition pore. The aim of this study was to verify the role of GSK-3 using a targeted mouse line lacking the critical N-terminal serine within GSK-3β (Ser9) and the highly homologous GSK-3α (Ser21), which when phosphorylated results in kinase inactivation. Postconditioning with 10 cycles of 5 seconds of reperfusion/5 seconds of ischemia and preconditioning with 6 cycles of 4 minutes of ischemia/6 minutes of reperfusion, similarly reduced infarction of the isolated perfused mouse heart in response to 30 minutes of global ischemia and 120 minutes of reperfusion. Preconditioning caused noticeable inactivating phosphorylation of GSK-3. However, both preconditioning and postconditioning still protected hearts of homozygous GSK-3 double knockin mice. Moreover, direct pharmacological inhibition of GSK-3 catalytic activity with structurally diverse inhibitors before or after ischemia failed to recapitulate conditioning protection. Nonetheless, cyclosporin A, a direct mitochondrial permeability transition pore inhibitor, reduced infarction in hearts from both wild-type and homozygous GSK-3 double knockin mice. Furthermore, in adult cardiac myocytes from GSK-3 double knockin mice, insulin exposure was still as effective as cyclosporin A in delaying mitochondrial permeability transition pore opening. Our results, which include a novel genetic approach, suggest that the inhibition of GSK-3 is unlikely to be the key determinant of cardioprotective signaling in either preconditioning or postconditioning in the mouse.
Unexpected Structural and Functional Consequences of the R33Q Homozygous Mutation in Cardiac Calsequestrin
Authors: Rizzi Nicoletta , Liu Nian , Napolitano Carlo , Nori Alessandra , Turcato Federica , Colombi Barbara , Bicciato Silvio , Arcelli Diego , Spedito Alessandro , Scelsi Mario , Villani Laura , Esposito Giovanni , Boncompagni Simona , Protasi Feliciano , Volpe Pompeo , Priori Silvia G.
Published: June 2008

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disorder characterized by life threatening arrhythmias elicited by physical and emotional stress in young individuals. The recessive form of CPVT is associated with mutation in the cardiac calsequestrin gene (
CASQ2
). We engineered and characterized a homozygous
CASQ2
R33Q/R33Q
mouse model that closely mimics the clinical phenotype of CPVT patients.
CASQ2
R33Q/R33Q
mice develop bidirectional VT on exposure to environmental stress whereas
CASQ2
R33Q/R33Q
myocytes show reduction of the sarcoplasmic reticulum (SR) calcium content, adrenergically mediated delayed (DADs) and early (EADs) afterdepolarizations leading to triggered activity. Furthermore triadin, junctin, and CASQ2-R33Q proteins are significantly decreased in knock-in mice despite normal levels of mRNA, whereas the ryanodine receptor (RyR2), calreticulin, phospholamban, and SERCA2a-ATPase are not changed. Trypsin digestion studies show increased susceptibility to proteolysis of mutant CASQ2. Despite normal histology,
CASQ2
R33Q/R33Q
hearts display ultrastructural changes such as disarray of junctional electron-dense material, referable to CASQ2 polymers, dilatation of junctional SR, yet normal total SR volume. Based on the foregoings, we propose that the phenotype of the
CASQ2
R33Q/R33Q
CPVT mouse model is portrayed by an unexpected set of abnormalities including (1) reduced CASQ2 content, possibly attributable to increased degradation of CASQ2-R33Q, (2) reduction of SR calcium content, (3) dilatation of junctional SR, and (4) impaired clustering of mutant CASQ2.
The del22q11.2 Candidate Gene
Tbx1
Controls Regional Outflow Tract Identity and Coronary Artery Patterning
Authors: Théveniau-Ruissy Magali , Dandonneau Mathieu , Mesbah Karim , Ghez Olivier , Mattei Marie-Geneviève , Miquerol Lucile , Kelly Robert G.
Published: June 2008

TBX1
, encoding a T-box containing transcription factor, is the major candidate gene for del22q11.2 or DiGeorge syndrome, characterized by craniofacial and cardiovascular defects including tetralogy of Fallot and common arterial trunk. Mice lacking
Tbx1
have severe defects in the development of pharyngeal derivatives including cardiac progenitor cells of the second heart field that contribute to the arterial pole of the heart. The outflow tract of
Tbx1
mutant embryos is short and narrow resulting in common arterial trunk. Here we show by a series of genetic crosses using transgene markers of second heart field derived myocardium and coronary endothelial cells that a subdomain of myocardium normally observed at the base of the pulmonary trunk is reduced and malpositioned in
Tbx1
mutant hearts. This defect is associated with anomalous coronary artery patterning. Both right and left coronary ostia form predominantly at the right/ventral sinus in mutant hearts, proximal coronary arteries coursing across the normally coronary free ventral region of the heart. We have identified
Semaphorin3c
as a
Tbx1
-dependent gene expressed in subpulmonary myocardium. Our results implicate second heart field development in coronary artery patterning and provide new insights into the association between conotruncal defects and coronary artery anomalies.
Role of Sphingosine-1-Phosphate Phosphohydrolase 1 in the Regulation of Resistance Artery Tone
Authors: Peter Bernhard Friedrich , Lidington Darcy , Harada Aki , Bolz Hanno Jörn , Vogel Lukas , Heximer Scott , Spiegel Sarah , Pohl Ulrich , Bolz Steffen-Sebastian
Published: June 2008

Sphingosine-1-phosphate (S1P), which mediates pleiotropic actions within the vascular system, is a prominent regulator of microvascular tone. By virtue of its S1P-degrading function, we hypothesized that S1P-phosphohydrolase 1 (SPP1) is an important regulator of tone in resistance arteries. Hamster gracilis muscle resistance arteries express mRNA encoding SPP1. Overexpression of SPP1 (via transfection of a SPP1
wt
) reduced resting tone, Ca
2+
sensitivity, and myogenic vasoconstriction, whereas reduced SPP1 expression (antisense oligonucleotides) yielded the opposite effects. Expression of a phosphatase-dead mutant of SPP1 (SPP1
H208A
) had no effect on any parameter tested, suggesting that catalytic activity of SPP1 is critical. The enhanced myogenic tone that follows overexpression of S1P-generating enzyme sphingosine kinase 1 (Sk1
wt
) was functionally antagonized by coexpression with SPP1
wt
but not SPP1
H208A
. SPP1 modulated vasoconstriction in response to 1 to 100 nmol/L exogenous S1P, a concentration range that was characterized as S1P
2
-dependent, based on the effect of S1P
2
inhibition by antisense oligonucleotides and 1 μmol/L JTE013. Inhibition of the cystic fibrosis transmembrane regulator (CFTR) (1) restored S1P responses that were attenuated by SPP1
wt
overexpression; (2) enhanced myogenic vasoconstriction; but (3) had no effect on noradrenaline responses. We conclude that SPP1 is an endogenous regulator of resistance artery tone that functionally antagonizes the vascular effects of both Sk1
wt
and S1P
2
receptor activation. SPP1 accesses extracellular S1P pools in a manner dependent on a functional CFTR transport protein. Our study assigns important roles to both SPP1 and CFTR in the physiological regulation of vascular tone, which influences both tissue perfusion and systemic blood pressure.
Localized α4 Integrin Phosphorylation Directs Shear Stress–Induced Endothelial Cell Alignment
Authors: Goldfinger Lawrence E. , Tzima Eleni , Stockton Rebecca , Kiosses William B. , Kinbara Kayoko , Tkachenko Eugene , Gutierrez Edgar , Groisman Alex , Nguyen Phu , Chien Shu , Ginsberg Mark H.
Published: June 2008

Vascular endothelial cells respond to laminar shear stress by aligning in the direction of flow, a process which may contribute to atheroprotection. Here we report that localized α4 integrin phosphorylation is a mechanism for establishing the directionality of shear stress–induced alignment in microvascular endothelial cells. Within 5 minutes of exposure to a physiological level of shear stress, endothelial α4 integrins became phosphorylated on Ser
988
. In wounded monolayers, phosphorylation was enhanced at the downstream edges of cells relative to the source of flow. The shear-induced α4 integrin phosphorylation was blocked by inhibitors of cAMP-dependent protein kinase A (PKA), an enzyme involved in the alignment of endothelial cells under prolonged shear. Moreover, shear-induced localized activation of the small GTPase Rac1, which specifies the directionality of endothelial alignment, was similarly blocked by PKA inhibitors. Furthermore, endothelial cells bearing a nonphosphorylatable α4(S
988
A) mutation failed to align in response to shear stress, thus establishing α4 as a relevant PKA substrate. We thereby show that shear-induced PKA-dependent α4 integrin phosphorylation at the downstream edge of endothelial cells promotes localized Rac1 activation, which in turn directs cytoskeletal alignment in response to shear stress.