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Coincident
Terms modified by Coincident Selected AbstractsTorsade de pointes in a patient with complex medical and psychiatric conditions receiving low-dose quetiapineACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2005W. V. R. Vieweg Objective:, Describe potential cardiac complications of low-dose quetiapine and other atypical antipsychotic drugs. Method:, We present a case report of a 45-year-old Black woman with multiple medical and psychiatric problems taking low-dose quetiapine. Results:, Coincident with a generalized seizure, the patient developed ,ventricular fibrillation'. She was countershocked with restoration of normal sinus rhythm. The initial electrocardiogram showed QT interval prolongation. Shortly thereafter, classical torsade de pointes appeared, lasted 10 min, and resolved spontaneously. Hypomagnesemia was present. A cardiac electrophysiologist was concerned that the very slow shortening of the prolonged QTc interval after magnesium replacement implicated quetiapine as a risk factor for QTc interval prolongation and torsade de pointes. A psychosomatic medicine consultant asserted that the fragmented medical and psychiatric care almost certainly contributed to the patient's medical problems. We discuss other cases of QT interval prolongation by newer antipsychotic drugs and previous reports by our group concerning the association of psychotropic drugs, QT interval prolongation, and torsade de pointes. Conclusion:, Atypical antipsychotic drug administration, when accompanied by risk factors, may contribute to cardiac arrhythmias including torsade de pointes. [source] Mrp2 modulates the activity of chloride channels in isolated hepatocytesHEPATOLOGY, Issue 1 2002Xinhua Li Adenosine triphosphate binding cassette family transport proteins are important organic ion transporters in hepatocytes but these molecules may also exhibit other functions. In the present study we have measured the effects of substrates of the canalicular organic ion transporter multidrug resistance associated protein 2 (Mrp2) on chloride channel activation and cell volume regulation. We found that substrates such as leukotriene D4, 17-,-estradiol glucuronide, and the leukotriene inhibitor MK-571 accelerated the activation of chloride channels by cell swelling and activated chloride channels in cytokine-pretreated hepatocytes. Two conjugated estrogens that are not Mrp2 substrates did not produce this effect. Hepatocytes derived from a strain of transport-deficient rats (TR,), which lack Mrp2 expression, showed none of these substrate effects. Coincident with their ability to activate channels, the Mrp2 substrates increased the rate of volume regulatory decrease by approximately 50% (P < .01), confirming that enhanced channel activation under this condition stimulated volume regulation. In TR-hepatocytes the Mrp2 substrate had no effect on volume regulation. In conclusion, Mrp2 plays a role in regulation of chloride channel function by reducing the lag time necessary for channel activation and consequently accelerating the process of cell volume regulation. Substrates of Mrp2 affect the ability of the protein to interact with chloride channels. These findings represent an alternative function of Mrp2 in hepatocytes. [source] Murid herpesvirus-4 induces chronic inflammation of intrahepatic bile ducts in mice deficient in gamma-interferon signallingHEPATOLOGY RESEARCH, Issue 2 2009Babunilayam Gangadharan Aim:, Infection of gamma interferon receptor defective mice with murid herpesvirus-4 also known as murine gammaherpesvirus-68 results in multi-organ fibrosis. In this paper we characterise the pathological changes occurring in the liver in this model. Methods:, Standard immunohistochemistry and in situ hybridisation techniques were used to identify the cellular changes and the presence of virus at different times post infection. Results:, In liver sections from infected gamma interferon receptor defective mice sampled on day 16 to at least day 120, 79% showed proliferating intrahepatic bile ducts associated with a chronic mononuclear cell inflammation. Only 8% of wild type mice showed similar lesions. Coincident with the inflammatory response bile duct epithelial cells were positive for arginase 1. Around day 50 post infection onwards focal fibrotic lesions appeared in approximately 30% of gamma interferon receptor defective mice resulting in destruction of intrahepatic bile ducts. In contrast to the chronic persisting inflammatory response the presence of virus infected cells were only observed between day 12,20 post-infection. Conclusion:, Infection of gamma interferon receptor defective mice with a murine gammaherpesvirus initiates a chronic persisting inflammatory response with a pathological profile similar to the human fibrotic liver disorder Primary Sclerosing Cholangitis. [source] Performance evaluation of the New Connecticut Leading Employment Index using lead profiles and BVAR modelsJOURNAL OF FORECASTING, Issue 6 2006Anirvan Banerji Abstract The leading and coincident employment indexes for the state of Connecticut developed following the recession of the early 1990s fell short of expectations. This paper performs two tasks. First, it describes the process of revising the Connecticut Coincident and Leading Employment Indexes. Second, it analyzes the statistical properties and performance of the new indexes by comparing the lead profiles of the new and old indexes as well as their out-of-sample forecasting performance, using the Bayesian Vector Autoregressive (BVAR) method. The new coincident index shows improved performance in dating employment cycle chronologies. The lead profile test demonstrates that superiority in a rigorous, non-parametric statistic fashion. The mixed evidence on the BVAR forecasting experiments illustrates that leading indexes properly predict cycle turning points and do not necessarily provide accurate forecasts except at turning points, a view that our results support.,,Copyright © 2006 John Wiley & Sons, Ltd. [source] Hormonal control of somatic cell oocyte interactions during ovarian follicle development,MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 3 2004Catherine M.H. Combelles Abstract In the mammalian ovarian follicle, paracrine signaling between the oocyte and somatic granulosa cells is bidirectional but the structural basis and physiological regulations of communication between gametic and somatic compartments remain unknown. The present experiments were designed to test the hypothesis that follicle stimulating hormone (FSH) regulates the ability of granulosa cells to make connections with the oocyte. We show that in prepubertal unprimed mice and mice carrying a targeted deletion of the FSH, subunit gene, granulosa cells exhibit orientation towards the oocyte manifest by the elaboration of transzonal projections (TZPs) and "apical" centrosome positioning at sites of granulosa-zona contact. In vivo FSH treatment results in a retraction of TZPs. Coincident with TZP retraction induced by FSH are changes in oocyte transcriptional activity and meiotic competence, which suggests one means by which the oocyte-granulosa cell dialogue may be modulated during development of ovarian follicles. Mol. Reprod. Dev. 69: 347,355, 2004. © 2004 Wiley-Liss, Inc. [source] Coincident, 100 kpc scale damped Ly, absorption towards a binary QSO: how large are galaxies at z, 3?MONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 3 2007Sara L. Ellison ABSTRACT We report coincident damped Ly, (DLA) and sub-DLA absorption at zabs= 2.66 and zabs= 2.94 towards the z, 3, 13.8 arcsec separation binary quasar SDSS 1116+4118 AB. At the redshifts of the absorbers, this angular separation corresponds to a proper transverse separation of ,110 h,170 kpc. A third absorber, a sub-DLA at zabs= 2.47, is detected towards SDSS 1116+4118 B, but no corresponding high column density absorber is present towards SDSS 1116+4118 A. We use high-resolution galaxy simulations and a clustering analysis to interpret the coincident absorption and its implications for galaxy structure at z, 3. We conclude that the common absorption in the two lines of sight is unlikely to arise from a single galaxy, or a galaxy plus satellite system, and is more feasibly explained by a group of two or more galaxies with separations ,100 kpc. The impact of these findings on single line-of-sight observations is also discussed; we show that abundances of DLAs may be affected by up to a few tenths of a dex by line-of-sight DLA blending. From a Keck Echellette Spectrograph and Imager spectrum of the two quasars, we measure metal column densities for all five absorbers and determine abundances for the three absorbers with log N(H i) > 20. For the two highest N(H i) absorbers, we determine high levels of metal enrichment, corresponding to 1/3 and 1/5 Z,. These metallicities are amongst the highest measured for DLAs at any redshift and are consistent with values measured in Lyman-break galaxies at 2 < z < 3. For the DLA at zabs= 2.94 we also infer an approximately solar ratio of ,-to-Fe peak elements from [S/Zn]=+0.05, and measure an upper limit for the molecular fraction in this particular line of sight of log f (H 2) < ,5.5. [source] , -secretase inhibitors exerts antitumor activity via down-regulation of Notch and Nuclear factor kappa B in human tongue carcinoma cellsORAL DISEASES, Issue 6 2007J Yao Objective:, To investigate the effect of the , -secretase inhibitors (GSIs) on the growth of human tongue carcinoma cells and to provide the molecular mechanism for potential application of GSIs in the treatment of tongue carcinoma. Materials and methods:, Human tongue carcinoma Tca8113 cells were cultured with the GSI L-685 458. Cell growth was determined by the methylthiazole tetrazolium method. Cell cycle and apoptosis were analyzed by flow cytometry and/or confocal microscopy. RT-PCR and Western blot were employed to determine the intracellular expression levels. Nuclear factor kappa B (NF- ,B) activation was examined by electrophoretic mobility shift assay. Results:, L-685,458 dose-dependently inhibited the growth of human tongue carcinoma Tca8113 cells by inducing G0,G1 cell cycle arrest and apoptosis. The mRNA and protein levels of Hairy/Enhancer of Split-1, a target of Notch activation, were decreased dose-dependently by L-685,458. Furthermore, L-685,458 down-regulated cyclin D1, B-cell lymphocytic-leukemia proto-oncogene 2 and c-Myc expressions, which are regulated by the transcription factor NF- ,B. Coincident with this observation, L-685,458 induced a dose-dependent reduction of constitutive NF- ,B activation in Tca8113 cells. Conclusions:, The GSI L-685,458 may have a therapeutic value for the treatment of human tongue carcinoma. Moreover, the effects of L-685,458 in tumor inhibition may act partially via the modulation of Notch and NF- ,B. [source] Impact of regulatory labeling for troglitazone and rosiglitazone on hepatic enzyme monitoring compliance: findings from the state of Ohio medicaid program,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2005Robert J. Cluxton Jr PharmD Abstract Purpose Troglitazone, the first drug of the thiazolidinediones class for type II diabetes, was first marketed in March 1997 and was removed from the U.S. market 36 months later after 90 cases of liver failure were reported despite multiple warnings containing liver enzyme monitoring recommendations. Rosiglitazone has been available since June 1999 and is still on the market. The purpose of this study was to evaluate the impact of labeled hepatic enzyme monitoring for troglitazone and rosiglitazone. Methods Drug cohorts were assembled, using population-based fee-for-service Medicaid claims, for patients between 18 and 65 years of age who had received at least one troglitazone (n,=,7226) or rosiglitazone (n,=,1480) prescription between 1 April, 1997, and 21 March, 2000. The outcome of interest was the percentage of patients, based on their first treatment episode, who had baseline and post-baseline liver enzyme testing. Results Overall baseline testing was under 9% before regulatory actions, increased to 14% after the first two ,Dear Doctor' letters issued by the FDA in October and December 1997, and peaked to about 26% afterwards. Coincident with the marketing of rosiglitazone and the fourth ,Dear Doctor' letter issued in June 1999, baseline testing dropped to 18%. Baseline testing increased 2.5-fold (race-sex-age adjusted) after regulatory action. Achieving 50% post-baseline testing took approximately 6 months for both drugs. Conclusion Regulatory actions had only modest effects on the incidence of liver monitoring. More effective and timely communication strategies, health provider prescribing interventions and modification of health provider behaviors to enhance compliance with recommended risk management measures need to be identified, evaluated and implemented. Copyright © 2004 John Wiley & Sons, Ltd. [source] Methadone and Buprenorphine Toxicity in ChildrenTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 1 2010Edward W. Boyer MD Recent years have seen very large increases in the prescribing of methadone and buprenorphine formulations for treatment of opioid addiction as well as the increasing utilization of methadone for the treatment of chronic pain. Coincident with the rise in the prescribing of these drugs has been a substantial increase in pediatric opioid toxicities and adverse events. This review will address the current state of methadone- and buprenorphine-related adverse events in children in the United States. We will also discuss treatment of opioid toxicity in pediatric populations and make recommendations aimed at reducing these occurrences.,(Am J Addict 2009;19:89,95) [source] Contractual governance, business groups and transitionTHE ECONOMICS OF TRANSITION, Issue 2 2002Raja Kali We suggest a unified framework to explain the following stylized pattern in the development of contractual governance and industrial organization. Contractual governance in many emerging economies is characterized by relational contracting. Coincident with relational contracts are large, diversified organizations , often referred to as business groups. As institutions and market intermediaries develop, a process of transition from relational contracting to arms-length explicit contracting takes place. During this phase relational and explicit contracts complement each other. Business groups initially expand in size, scope and increase the strength of ties. As development proceeds, a threshold is crossed after which business groups begin to unravel. This process of transition in contractual governance is often accompanied by a period of rapid growth, which eventually comes to a stop. JEL classification: L22, L14, O17. [source] Access and Outcomes Among Minority Transplant Patients, 1999,2008, with a Focus on Determinants of Kidney Graft SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4p2 2010P.-Y. Fan Coincident with an increasing national interest in equitable health care, a number of studies have described disparities in access to solid organ transplantation for minority patients. In contrast, relatively little is known about differences in posttransplant outcomes between patients of specific racial and ethnic populations. In this paper, we review trends in access to solid organ transplantation and posttransplant outcomes by organ type, race and ethnicity. In addition, we present an analysis of categories of factors that contribute to the racial/ethnic variation seen in kidney transplant outcomes. Disparities in minority access to transplantation among wait-listed candidates are improving, but persist for those awaiting kidney, simultaneous kidney and pancreas and intestine transplantation. In general, graft and patient survival among recipients of solid organ transplants is highest for Asians and Hispanic/Latinos, intermediate for whites and lowest for African Americans. Although much of the difference in outcomes between racial/ethnic groups can be accounted for by adjusting for patient characteristics, important observed differences remain. Age and duration of pretransplant dialysis exposure emerge as the most important determinants of survival in an investigation of the relative impact of center-related versus patient-related variables on kidney graft outcomes. [source] Dispersal of Desiccation-Sensitive Seeds is not Coincident with High Rainfall in a Seasonal Tropical Forest in AustraliaBIOTROPICA, Issue 3 2010James P. Hill ABSTRACT We tested the hypothesis that dispersal periods of recalcitrant seeded species were coincident with the wet season in a seasonal tropical forest in Australia. Unlike similar forests, we found no support for this pattern. Intensification of seasonal aridity may increase mortality in desiccation-sensitive seeds. [source] Increased Cerebral Blood Flow And Cardiac Output Following Cerebral Arterial Air Embolism In SheepCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2001David J Williams SUMMARY 1. The effects of cerebral arterial gas embolism on cerebral blood flow and systemic cardiovascular parameters were assessed in anaesthetized sheep. 2. Six sheep received a 2.5 mL injection of air simultaneously into each common carotid artery over 5 s. Mean arterial blood pressure, heart rate, end-tidal carbon dioxide and an ultrasonic Doppler index of cerebral blood flow were monitored continuously. Cardiac output was determined by periodic thermodilution. 3. Intracarotid injection of air produced an immediate drop in mean cerebral blood flow. This drop was transient and mean cerebral blood flow subsequently increased to 151% before declining slowly to baseline. Coincident with the increased cerebral blood flow was a sustained increase in mean cardiac output to 161% of baseline. Mean arterial blood pressure, heart rate and end-tidal carbon dioxide were not significantly altered by the intracarotid injection of air. 4. The increased cardiac output is a pathological response to impact of arterial air bubbles on the brain, possibly the brainstem. The increased cerebral blood flow is probably the result of the increased cardiac output and dilation of cerebral resistance vessels caused by the passage of air bubbles. [source] The Late Prehistoric,Early Historic Game Sink in the Northwestern United StatesCONSERVATION BIOLOGY, Issue 1 2002R. Lee Lyman The number of big game killed by the Corps of Discovery in 1805,1806 and recorded by Lewis and Clark suggests that ungulates were abundant in central and eastern Montana and rare in western Montana, central Idaho, and southeastern Washington during the early nineteenth century. Paleoecologists Paul Martin and Chris Szuter conclude that this difference was a function of human predation. They support their conclusion that ungulates would have been abundant in southeastern Washington had humans not hunted them by arguing that the nineteenth-century livestock industry was successful without supplemental feeding. The livestock industry was, however, not consistently successful until artificial feeding was initiated. Archaeological data from eastern Washington indicate that ungulates have been taken by human hunters more frequently than small-mammal prey throughout the last 10,000 years and that ungulates decreased relative to small mammals coincident with changes in climate. Bison ( Bison bison) and elk (Cervus canadensis) were present in eastern Washington throughout the Holocene, but bison were abundant there only during a cooler and moister period; elk have been abundant only in the twentieth century, subsequent to transplants and the extermination of predators. Geographic variation in the abundance of bison across Montana, Idaho, and eastern Washington has been influenced by human predation but has also been influenced by biogeographic history, habitat differences, and climatic change. Resumen: Los datos históricos proveen información valiosa sobre las estructuras de los ecosistemas, sus funciones y procesos. El número de animales de caza grandes que fueron sacrificados por las tropas de descubrimiento en 1805-1806 y registradas por Lewis y Clark sugieren que los ungulados eran abundantes en Montana central y oriental y raros en Montana occidental, Idaho central y el sudeste de Washington durante los inicios del siglo diecinueve. Los paleontólogos Paul Martin y Chris Szuter concluyen que esta diferencia fue causada por la depredación humana. Ellos apoyan su conclusión de que los ungulados podrían haber sido abundantes en el sudeste de Washington si los humanos no los hubieran cazado argumentando que la industria de la ganadería del siglo diecinueve exitosa sin alimento suplementario. Sin embargo, la industria de la ganadería no fue consistentemente exitosa hasta que se inició la alimentación artificial. Los datos arqueológicos de Washington oriental indican que los ungulados fueron eliminados por los cazadores humanos mas frecuentemente que las presas pequeñas de mamíferos a lo largo de los últimos 10,000 años y que la disminución de ungulados, relativa a la de mamíferos pequeños coincidió con cambios en el clima. El bisonte (Bison bison) y el alce (Cervus canadiensis) estuvieron presentes en Washington oriental a lo largo del Holoceno, pero los bisontes fueron abundantes solo durante un periodo mas frío y húmedo; los alces habían sido abundantes solo en el siglo veinte subsecuente a los transplantes y a la exterminación de los depredadores. La variación en la abundancia de alces a lo largo de Montana, Idaho y el oriente de Washington estuvo influenciada por la depredación humana, pero también por la historia biogeográfica, las diferencias en hábitat y el cambio climático. [source] Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesionCYTOSKELETON, Issue 1 2005Tony Yeung Abstract The morphology and cytoskeletal structure of fibroblasts, endothelial cells, and neutrophils are documented for cells cultured on surfaces with stiffness ranging from 2 to 55,000 Pa that have been laminated with fibronectin or collagen as adhesive ligand. When grown in sparse culture with no cell-cell contacts, fibroblasts and endothelial cells show an abrupt change in spread area that occurs at a stiffness range around 3,000 Pa. No actin stress fibers are seen in fibroblasts on soft surfaces, and the appearance of stress fibers is abrupt and complete at a stiffness range coincident with that at which they spread. Upregulation of ,5 integrin also occurs in the same stiffness range, but exogenous expression of ,5 integrin is not sufficient to cause cell spreading on soft surfaces. Neutrophils, in contrast, show no dependence of either resting shape or ability to spread after activation when cultured on surfaces as soft as 2 Pa compared to glass. The shape and cytoskeletal differences evident in single cells on soft compared to hard substrates are eliminated when fibroblasts or endothelial cells make cell-cell contact. These results support the hypothesis that mechanical factors impact different cell types in fundamentally different ways, and can trigger specific changes similar to those stimulated by soluble ligands. Cell Motil. Cytoskeleton 60:24,34, 2005. © 2004 Wiley-Liss, Inc. [source] Periostin promotes a fibroblastic lineage pathway in atrioventricular valve progenitor cellsDEVELOPMENTAL DYNAMICS, Issue 5 2009Russell A. Norris Abstract Differentiation of prevalvular mesenchyme into valve fibroblasts is an integral step towards the development of functionally mature cardiac valves. Although clinically relevant, little is known regarding the molecular and cellular mechanisms by which this process proceeds. Genes that are regulated in a spatio-temporal pattern during valve remodeling are candidates for affecting this differentiation process. Based on its expression pattern, we have focused our studies on the role of the matricellular gene, periostin, in regulating the differentiation of cushion mesenchymal cells into valve fibroblasts. Herein, we demonstrate that periostin expression is coincident with and regulates type I collagen protein production, a major component of mature valve tissue. Adenoviral-mediated knock-down of periostin in atrioventricular mesenchyme resulted in a decrease in collagen I protein expression and aberrant induction of myocyte markers indicating an alteration in AV mesenchyme differentiation. In vitro analyses using a novel "cardiotube" assay further demonstrated that expression of periostin regulates lineage commitment of valve precursor cells. In these cells, expression of periostin and collagen I are regulated, in part, by TGF,-3. We further demonstrate that TGF,-3, through a periostin/collagen pathway, enhances the viscoelastic properties of AV cushion tissue surface tension and plays a crucial role in regulating valve remodeling. Thus, data presented here demonstrate that periostin, a TGF,-3 responsive gene, functions as a crucial mediator of chick AV valve maturation via promoting mesenchymal-to-fibroblast differentiation while blocking differentiation of alternative cell types (myocytes). Developmental Dynamics 238:1052,1063, 2009. © 2009 Wiley-Liss, Inc. [source] Zebrafish dou yan mutation causes patterning defects and extensive cell death in the retinaDEVELOPMENTAL DYNAMICS, Issue 5 2007Anne E. Catalano Abstract The size of an organ is largely determined by the number of cells it contains, which in turn is regulated by two opposing processes, cell proliferation and cell death, however, it is generally not clear how cell proliferation and cell death are coordinated during development. Here, we characterize the zebrafish dou yanmi234 mutation that results in a dramatic reduction of retinal size and a disruption of retinal differentiation and lamination. The retinal size reduction is caused by increased retinal cell death in a non,cell-autonomous manner during early development. The phenotypic defect in dou yanmi234 arises coincident with the onset of retinal neurogenesis and differentiation. Interestingly, unlike many other small eye mutations, the mutation does not increase the level of cell death in the brain, suggesting that the brain and retina use different mechanisms to maintain cell survival. Identification and further study of the dou yan gene will enhance our understanding of the molecular mechanisms regulating retinal cellular homeostasis, i.e., the balance between cell proliferation and cell death. Developmental Dynamics 236:1295,1306, 2007. © 2007 Wiley-Liss, Inc. [source] Inhibition of SMAD2 expression prevents murine palatal fusionDEVELOPMENTAL DYNAMICS, Issue 7 2006Nobuyuki Shiomi Abstract Transforming growth factor (TGF)-beta 3 is known to regulate the disappearance of murine medial edge epithelium (MEE) during palatal fusion. Our previous studies showed that SMAD2, a TGF-beta signaling mediator, was expressed and phosphorylated primarily in the MEE and that SMAD2 phosphorylation in the MEE was temporospatially regulated by TGF-beta 3. The goal of this study was to examine the requirement for SMAD2 to complete the developmental events necessary for palatal fusion. SMAD2 expression was inhibited with Smad2 siRNA transfection into palatal tissues in vitro. The results showed that Smad2 siRNA transfection resulted in the maintenance of MEE cells in the palatal midline. Western blot and immunofluorescence analyses confirmed that the endogenous SMAD2 and phospho-SMAD2 levels were reduced following siRNA transfection. The SMAD3 level was not altered by the Smad2 siRNA transfection. The persistence of the MEE and the decreased SMAD2/phospho-SMAD2 levels were coincident with increased MEE cell proliferation. Addition of exogenous TGF-beta 3 increased p-SMAD2 level but not the total SMAD2 level. Therefore, exogenous TGF-beta 3 was not able to induce p-SMAD2 enough to rescue the palatal phenotype in the Smad2 siRNA group. The results indicated that the endogenous SMAD2 level is crucial in the regulation of disappearance of MEE during palatal fusion. Developmental Dynamics 235:1785,1793, 2006. © 2006 Wiley-Liss, Inc. [source] Analysis of N-cadherin function in limb mesenchymal chondrogenesis in vitro,DEVELOPMENTAL DYNAMICS, Issue 2 2002Anthony M. Delise Abstract During embryonic limb development, cartilage formation is presaged by a crucial mesenchymal cell condensation phase. N-Cadherin, a Ca2+ -dependent cell,cell adhesion molecule, is expressed in embryonic chick limb buds in a spatiotemporal pattern suggestive of its involvement during cellular condensation; functional blocking of N-cadherin homotypic binding, by using a neutralizing monoclonal antibody, results in perturbed chondrogenesis in vitro and in vivo. In high-density micromass cultures of embryonic limb mesenchymal cells, N-cadherin expression level is high during days 1 and 2, coincident with active cellular condensation, and decreases upon overt chondrogenic differentiation from day 3 on. In this study, we have used a transfection approach to evaluate the effects of gain- and loss-of-function expression of N-cadherin constructs on mesenchymal condensation and chondrogenesis in vitro. Chick limb mesenchymal cells were transfected by electroporation with recombinant expression plasmids encoding wild-type or two mutant extracellular/cytoplasmic deletion forms of N-cadherin. Expression of the transfected N-cadherin forms showed a transient profile, being high on days 1,2 of culture, and decreasing by day 3, fortuitously coincident with the temporal profile of endogenous N-cadherin gene expression. Examined by means of peanut agglutinin (PNA) staining for condensing precartilage mesenchymal cells, cultures overexpressing wild-type N-cadherin showed enhanced cellular condensation on culture days 2 and 3, whereas expression of the deletion mutant forms (extracellular/cytoplasmic) of N-cadherin resulted in a decrease in PNA staining, suggesting that a complete N-cadherin protein is required for normal cellular condensation to occur. Subsequent chondrogenesis was also affected. Cultures overexpressing the wild-type N-cadherin protein showed enhanced chondrogenesis, indicated by increased production of cartilage matrix (sulfated proteoglycans, collagen type II, and cartilage proteoglycan link protein), as well as increased cartilage nodule number and size of individual nodules, compared with control cultures and cultures transfected with either of the two mutant N-cadherin constructs. These results demonstrate that complete N-cadherin function, at the levels of both extracellular homotypic binding and cytoplasmic linkage to the cytoskeleton by means of the catenin complex, is required for chondrogenesis by mediating functional mesenchymal cell condensation. © 2002 Wiley-Liss, Inc. [source] Activity of nAChRs containing ,9 subunits modulates synapse stabilization via bidirectional signaling programsDEVELOPMENTAL NEUROBIOLOGY, Issue 14 2009Vidya Murthy Abstract Although the synaptogenic program for cholinergic synapses of the neuromuscular junction is well known, little is known of the identity or dynamic expression patterns of proteins involved in non-neuromuscular nicotinic synapse development. We have previously demonstrated abnormal presynaptic terminal morphology following loss of nicotinic acetylcholine receptor (nAChR) ,9 subunit expression in adult cochleae. However, the molecular mechanisms underlying these changes have remained obscure. To better understand synapse formation and the role of cholinergic activity in the synaptogenesis of the inner ear, we exploit the nAChR ,9 subunit null mouse. In this mouse, functional acetylcholine (ACh) neurotransmission to the hair cells is completely silenced. Results demonstrate a premature, effusive innervation to the synaptic pole of the outer hair cells in ,9 null mice coinciding with delayed expression of cell adhesion proteins during the period of effusive contact. Collapse of the ectopic innervation coincides with an age-related hyperexpression pattern in the null mice. In addition, we document changes in expression of presynaptic vesicle recycling/trafficking machinery in the ,9 null mice that suggests a bidirectional information flow between the target of the neural innervation (the hair cells) and the presynaptic terminal that is modified by hair cell nAChR activity. Loss of nAChR activity may alter transcriptional activity, as CREB binding protein expression is decreased coincident with the increased expression of N-Cadherin in the adult ,9 null mice. Finally, by using mice expressing the nondesensitizing ,9 L9,T point mutant nAChR subunit, we show that increased nAChR activity drives synaptic hyperinnervation. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source] Relationship between GABAergic interneurons migration and early neocortical network activityDEVELOPMENTAL NEUROBIOLOGY, Issue 2-3 2009Ana D. de Lima Abstract Available evidence converges to suggest that during the early development of the cerebral cortex, the emergence of the spontaneous network activity chronologically overlap with the end of the cell migration period in the developing cortex. We approached the functional regulation of neuronal migration in a culture model of neocortical networks, using time lapses to detect migratory movements, calcium-imaging to assess the activity of migratory neurons, and immunocytochemical methods to identify the migratory cells retrospectively. In cell cultures, early physiological development and cell migration are reproduced at a local network level, thus allowing the study of the interrelationships between cell migration and network development independent of the topographical complexity. Neurons migrate at least until 12 days in vitro and GABAergic neurons migrate faster compared with non-GABAergic neurons. A decline of migratory activity was coincident with the development of spontaneous synchronous network activity. Migrating interneurons did not participate in synchronous network activity, but interneurons that ended cell migration during observation time frequently engaged in synchronous activity within less than an hour. Application of GABAA and ionotropic glutamate receptor antagonists significantly increased the number of migrating GABAergic neurons without changing the dynamics of the migratory movements. Thus, neurotransmitters released by early network activity might favor the termination of neuronal migration. These results reinforce the idea that network activity plays an important role in the development of late-born GABAergic cells. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source] In vivo dynamics of CNS sensory arbor formation: A time-lapse study in the embryonic leechDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2003Michael W. Baker Abstract In the embryo of the leech Hirudo medicinalis, afferent projections of peripheral sensory neurons travel along common nerve tracts to the CNS, where they defasciculate, branch, and arborize into separate, modality-specific synaptic laminae. Previous studies have shown that this process requires, at least in part, the constitutive and then modality-specific glycosylations of tractin, a leech L1 homologue. We report here on the dynamics of growth of these projections as obtained by examining the morphology of single growing dye-filled sensory afferents as a function of time. Using 2-photon laser-scanning microscopy of the intact developing embryo, we obtained images of individual sensory projections at 3 to 30 min intervals, over several hours of growth, and at different stages of development. The time-lapse series of images revealed a highly dynamic and maturation-state-dependent pattern of growth. Upon entering the CNS, the growth cone-tipped primary axon sprouted numerous long filopodial processes, many of which appeared to undergo repeated cycles of extension and retraction. The growth cone was transformed into a sensory arbor through the formation of secondary branches that extended within the ganglionic neuropil along the anterior-posterior axis of the CNS. Numerous tertiary and quaternary processes grew from these branches and also displayed cycles of extension and retraction. The motility of these higher-order branches changed with age, with younger afferents displaying higher densities and greater motility than older, more mature sensory arbors. Finally, coincident with a reduction in higher order projections was the appearance of concavolar structures on the secondary processes. Rows of these indentations suggest the formation of presynaptic en-passant specializations accompanying the developmental onset of synapse formation. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 41,53, 2003 [source] GABAergic modulation of primary gustatory afferent synaptic efficacyDEVELOPMENTAL NEUROBIOLOGY, Issue 2 2002Andrew A. Sharp Abstract Modulation of synaptic transmission at the primary sensory afferent synapse is well documented for the somatosensory and olfactory systems. The present study was undertaken to test whether GABA impacts on transmission of gustatory information at the primary afferent synapse. In goldfish, the vagal gustatory input terminates in a laminated structure, the vagal lobes, whose sensory layers are homologous to the mammalian nucleus of the solitary tract. We relied on immunoreactivity for the GABA-transporter, GAT-1, to determine the distribution of GABAergic synapses in the vagal lobe. Immunocytochemistry showed dense, punctate GAT-1 immunoreactivity coincident with the layers of termination of primary afferent fibers. The laminar nature and polarized dendritic structure of the vagal lobe make it amenable to an in vitro slice preparation to study early synaptic events in the transmission of gustatory input. Electrical stimulation of the gustatory nerves in vitro produces synaptic field potentials (fEPSPs) predominantly mediated by ionotropic glutamate receptors. Bath application of either the GABAA receptor agonist muscimol or the GABAB receptor agonist baclofen caused a nearly complete suppression of the primary fEPSP. Coapplication of the appropriate GABAA or GABAB receptor antagonist bicuculline or CGP-55845 significantly reversed the effects of the agonists. These data indicate that GABAergic terminals situated in proximity to primary gustatory afferent terminals can modulate primary afferent input via both GABAA and GABAB receptors. The mechanism of action of GABAB receptors suggests a presynaptic locus of action for that receptor. © 2002 Wiley Periodicals, Inc. J Neurobiol 52: 133,143, 2002 [source] Organization and mode of secretion of the granular prismatic microstructure of Entodesma navicula (Bivalvia: Mollusca)ACTA ZOOLOGICA, Issue 2 2009Elizabeth M. Harper The term homogeneous has been applied to molluscan microstructures that lack a readily discernible microstructure and as a result, it has become rather a ,dustbin' term, covering a multitude of unrelated finely crystalline textures. Here we investigate in detail the outer ,homogeneous' layer of the lyonsiid bivalve Entodesma navicula. The apparently equigranular crystals (up to 10 µm) are, in fact, short prisms which grow in a dense organic matrix with their c -axes and fibre axes coincident, perpendicular to the growth surface. These prisms are distinct from the aragonitic prisms grown by other bivalves in both their morphology and their mode of growth and so we propose the term granular prismatic microstructure. The organic content of granular prisms (7.4%) is the highest yet recorded for any molluscan microstructure and it is apparent that the short prisms have grown within a gel-filled space. Although this high organic content is likely to make the microstructure metabolically expensive to produce, it has the benefit of making the valves very flexible. This may be advantageous in the intertidal zone inhabited by E. navicula by allowing a tight seal between the valves. [source] Hydrologic and geomorphic effects of temporary ice-dammed lake formation during jökulhlaupsEARTH SURFACE PROCESSES AND LANDFORMS, Issue 7 2003Matthew J. Roberts Abstract Glacial outburst ,oods (jökulhlaups) occur frequently in glaciated environments, and the resultant ,ooding causes geomorphic change and, in some instances, damage to local infrastructure. During some jökulhlaups, ,oodwater is stored temporarily in ice-marginal locations. In July 1999, a linearly rising jökulhlaup burst from Sólheimajökull, Iceland. During this remarkable event, subglacial ,oodwater pooled transiently in two relict ice-dammed lake basins, before draining suddenly back into Sólheimajökull. The signi,cance of such rapid formation and attendant drainage of temporary ice-dammed lakes during jökulhlaups has not been addressed. Consequently, this paper: (i) assesses the hydrologic and geomorphic effects of temporary ice-dammed lake formation caused by lake-basin ,retro-,lling'; and (ii) discusses the impact and signi,cance of transient retro-,lling under jökulhlaup conditions. Pre- and post-,ood ,eldwork at Sólheimajökull enabled the impact and signi,cance of lake-basin retro-,lling to be assessed. Field evidence demonstrates that the July 1999 jökulhlaup had an unusually rapid rise to peak discharge, resulting in subglacial ,oodwater being purged to ice-marginal locations. The propensity for temporary retro-,lling was controlled by rapid expulsion of ,oodwater from Sólheimajökull, coincident with locations suitable for ,oodwater storage. Floodwater inundated both ice-marginal lake basins, permitting signi,cant volumes of sediment deposition. Coarse-grained deltas prograding from the ice margin and boulders perched on scoured bedrock provide geomorphic records of sudden retro-,lling. The depositional characteristics of lake-basin deposits at Sólheimajökull are similar to jökulhlaup sediments documented in proglacial settings elsewhere; however, their depositional setting and association with ice-marginal landforms is distinctive. Findings suggest that temporary ice-dammed lake formation and drainage has the capacity to alter the shape of the ,ood hydrograph, especially if drainage of a temporary lake is superimposed on the original jökulhlaup. Deposits associated with lake-basin retro-,lling have a long-term preservation potential that could help to identify temporary ice-dammed lake formation in modern and ancient glacial environments. Copyright © 2003 John Wiley & Sons, Ltd. [source] Local and regional-scale responses of ant diversity to a semiarid biome transitionECOGRAPHY, Issue 4 2001Brandon T. Bestelmeyer The locations of biome transitions and ecotones are frequently defined by the rapid shift from one form of dominant vegetation to another. The composition of animal taxa is predicted to shift in parallel with that of dominant plants and species diversity is predicted to he greater in transitional zones than in adjacent areas. We asked whether ant species diversity and composition supported these predictions across a biome transition between shortgrass steppe and Chihuahuan desert vegetation. Neither species richness nor diversity was highest at the biome transition region as a whole, or within habitats in the biome transition. The biome transition region was not intermediate in ant species composition or in the representation of different faunal complexes. The community similarity between matched habitats shared between the biome transition zone and adjacent regions was less than that between distinct habitats occurring within regions. A zoogeographic transition for ants may occur to the north of the phytogeographic transition and may be coincident with the northern limits of monsoonal precipitation patterns. In contrast, the phytogeographic transition may be related to less extreme climatic variation within the monsoonal region occurring further south. [source] Ecohydrological controls on snowmelt partitioning in mixed-conifer sub-alpine forestsECOHYDROLOGY, Issue 2 2009Noah P. Molotch Abstract We used co-located observations of snow depth, soil temperature, and moisture and energy fluxes to monitor variability in snowmelt infiltration and vegetation water use at mixed-conifer sub-alpine forest sites in the Valles Caldera, New Mexico (3020 m) and on Niwot Ridge, Colorado (3050 m). At both sites, vegetation structure largely controlled the distribution of snow accumulation with 29% greater accumulation in open versus under-canopy locations. Snow ablation rates were diminished by 39% in under-canopy locations, indicating increases in vegetation density act to extend the duration of the snowmelt season. Similarly, differences in climate altered snow-season duration, snowmelt infiltration and evapotranspiration. Commencement of the growing season was coincident with melt-water input to the soil and lagged behind springtime increases in air temperature by 12 days on average, ranging from 2 to 33 days under warmer and colder conditions, respectively. Similarly, the timing of peak soil moisture was highly variable, lagging behind springtime increases in air temperature by 42 and 31 days on average at the Colorado and New Mexico sites, respectively. Latent heat flux and associated evaporative loss to the atmosphere was 28% greater for the year with earlier onset of snowmelt infiltration. Given the large and variable fraction of precipitation that was partitioned into water vapour loss, the combined effects of changes in vegetation structure, climate and associated changes to the timing and magnitude of snowmelt may have large effects on the partitioning of snowmelt into evapotranspiration, surface runoff and ground water recharge. Copyright © 2009 John Wiley & Sons, Ltd. [source] Nocturnal migration of dragonflies over the Bohai Sea in northern ChinaECOLOGICAL ENTOMOLOGY, Issue 5 2006HONG-QIANG FENG Abstract 1.,A sudden increase and subsequent sharp decrease of catches of dragonflies in a searchlight trap, with Pantala flavescens Fabricius (Odonata: Libellulidae) predominating, observed at Beihuang Island in the centre of the Bohai Gulf, in 2003 and 2004, indicated a seasonal migration of these insects over the sea during the night in China. The movements were associated with the onset of fog. 2.,Simultaneous radar observations indicated that the nocturnally migrating dragonflies generally flew at altitudes of up to 1000 m above sea level, with high density concentrations at about 200,300 or 500 m; these concentrations were coincident with the temperature inversion. 3.,During early summer, the dragonflies oriented in a downwind direction, so that the displacement direction varied between different altitudes. In contrast, during late summer, the dragonflies were able to compensate for wind drift, even headwind drift, so as to orient south-westward no matter how the wind changed, and thus the displacement direction was towards the south-west. 4.,The duration of flight, estimated from the variation of area density derived from radar data and hourly catches in the searchlight trap through the night, was about 9,10 h. The displacement speed detected using radar was ,5,11 m s,1. Therefore, the dragonflies might migrate 150,400 km in a single flight. 5.,The dragonflies were thought to originate in Jiangsu province and they migrated into north-east China to exploit the temporary environment of paddy fields in early summer. Their offspring probably migrated back south during late summer and autumn. [source] Discontinuity in fish assemblages across an elevation gradient in a southern Appalachian watershed, USAECOLOGY OF FRESHWATER FISH, Issue 1 2005J. L. Robinson This region is noted for extreme topographical relief, high cumulative annual rainfall and many rare and endemic plants and animals. The study area encompasses a portion of the Blue Ridge Escarpment and the associated Brevard Fault Zone. We hypothesise that major waterfalls and cascade complexes have acted to limit invasion and colonisation by fishes from downstream. This hypothesis is supported by longitudinal fish assemblage patterns in our study streams. Fish species richness in Toxaway River increased from 4 to 23 between Lake Toxaway and Lake Jocassee, a distance of 10 river km. We found similar discontinuities in neighbouring Horsepasture River and Bearwallow Creek. We found no instances of species replacement along this elevation gradient, and the trend in increased diversity downstream showed discontinuities coincident with sharp elevation breaks. With regard to theories posited to explain community formation in headwater stream fish communities (especially in those characterised by high topographical relief), we suggest coloniser ,access' may be more important than other factors including competitive interactions. Resumen 1. En este estudio examinamos patrones en los ensamblajes de peces de los ríos Toxaway y Horsepasture, dos ríos de elevada altitud de Carolina del Norte (USA). Esta región se caracteriza por rupturas topografías extremas, gran cantidad de lluvia anual y numerosos endemismos animales y vegetales. El estudio incluye una porción de la región del Blue Ridge Escarpment y la zona asociada de Brevard Fault. 2. Nuestra hipótesis es que los complejos sistemas de cataratas han limitado la invasión y la colonización de los peces desde las localidades aguas abajo. Los patrones longitudinales de los ensamblajes de peces fueron consistentes con esta hipótesis. La riqueza de las especies de peces en el río Toxaway incrementó desde 4 a 23 especies en una distancia de 10 Km de río, entre los lagos Taxoway y Jocasee. Encontramos discontinuidades similares en los vecinos ríos Horsepasture y Bearwallow. No encontramos ningún caso de re-emplazamiento de especies a lo largo del gradiente de altitud y la tendencia a incrementar la diversidad aguas abajo mostró discontinuidades que coincidieron con rupturas de altitudes. 3. Al considerar teorías que explican la formación de comunidades en zonas altas de ríos (especialmente en regiones caracterizadas por rupturas topografías), sugerimos que el acceso para los colonizadores puede ser más importante que otros factores incluyendo interacciones competitivas. [source] Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansionEMBO MOLECULAR MEDICINE, Issue 6-7 2009Frédéric Varnat Abstract Human colon cancers often start as benign adenomas through loss of APC, leading to enhanced ,CATENIN (,CAT)/TCF function. These early lesions are efficiently managed but often progress to invasive carcinomas and incurable metastases through additional changes, the nature of which is unclear. We find that epithelial cells of human colon carcinomas (CCs) and their stem cells of all stages harbour an active HH-GLI pathway. Unexpectedly, they acquire a high HEDGEHOG-GLI (HH-GLI) signature coincident with the development of metastases. We show that the growth of CC xenografts, their recurrence and metastases require HH-GLI function, which induces a robust epithelial-to-mesenchymal transition (EMT). Moreover, using a novel tumour cell competition assay we show that the self-renewal of CC stem cells in vivo relies on HH-GLI activity. Our results indicate a key and essential role of the HH-GLI1 pathway in promoting CC growth, stem cell self-renewal and metastatic behavior in advanced cancers. Targeting HH-GLI1, directly or indirectly, is thus predicted to decrease tumour bulk and eradicate CC stem cells and metastases. [source] | ||||||||||||||||||||||||||||||||||||||||||||||||||||