bluuebunny/crossref_metadata_2025 huggingface dataset:
Notch Signaling Induces Osteogenic Differentiation and Mineralization of Vascular Smooth Muscle Cells
Authors: Shimizu Takehisa , Tanaka Toru , Iso Tatsuya , Doi Hiroshi , Sato Hiroko , Kawai-Kowase Keiko , Arai Masashi , Kurabayashi Masahiko
Published: May 2009

Objective—

Vascular calcification is closely correlated with cardiovascular morbidity and mortality. Here, we demonstrate the role of Notch signaling in osteogenic differentiation and mineralization of vascular smooth muscle cells (SMCs).

Methods and Results—

The Msx2 gene, a key regulator of osteogenesis, was highly induced by coculture with Notch ligand-expressing cells or overexpression of Notch intracellular domains (NICDs) in human aortic SMCs (HASMCs). Furthermore, the Notch1 intracellular domain (N1-ICD) overexpression markedly upregulated alkaline phosphatase (ALP) activity and matrix mineralization of HASMCs. A knockdown experiment with a small interfering RNA confirmed that Msx2 mediated N1-ICD–induced osteogenic conversion of HASMCs. Interestingly, Msx2 induction by N1-ICD was independent of bone morphogenetic protein–2 (BMP-2), an osteogenic morphogen upstream of Msx2. The transcriptional activity of the Msx2 promoter was significantly enhanced by N1-ICD overexpression. The RBP-Jk binding element within the Msx2 promoter was critical to Notch-induced Msx2 gene expression. Correspondingly, N1-ICD overexpression did not induce the Msx2 expression in RBP-Jk–deficient fibroblasts. Immunohistochemistry of human carotid artery specimens revealed localization of Notch1, Jagged1 and Msx2 to fibrocalcific atherosclerotic plaques.

Conclusion—

These results imply a new mechanism for osteogenic differentiation of vascular SMCs in which Notch/RBP-Jk signaling directly induces Msx2 gene expression and suggest its crucial role in mediating vascular calcification.
Genetically Determined Differences in Sodium Current Characteristics Modulate Conduction Disease Severity in Mice With Cardiac Sodium Channelopathy
Authors: Remme Carol Ann , Scicluna Brendon P. , Verkerk Arie O. , Amin Ahmad S. , van Brunschot Sandra , Beekman Leander , Deneer Vera H.M. , Chevalier Catherine , Oyama Fumitaka , Miyazaki Haruko , Nukina Nobuyuki , Wilders Ronald , Escande Denis , Houlgatte Rémi , Wilde Arthur A.M. , Tan Hanno L. , Veldkamp Marieke W. , de Bakker Jacques M.T. , Bezzina Connie R.
Published: May 2009

Conduction slowing of the electric impulse that drives the heartbeat may evoke lethal cardiac arrhythmias. Mutations in
SCN5A
, which encodes the pore-forming cardiac sodium channel α subunit, are associated with familial arrhythmia syndromes based on conduction slowing. However, disease severity among mutation carriers is highly variable. We hypothesized that genetic modifiers underlie the variability in conduction slowing and disease severity. With the aim of identifying such modifiers, we studied the
Scn5a
1798insD/+
mutation in 2 distinct mouse strains, FVB/N and 129P2. In 129P2 mice, the mutation resulted in more severe conduction slowing particularly in the right ventricle (RV) compared to FVB/N. Pan-genomic mRNA expression profiling in the 2 mouse strains uncovered a drastic reduction in mRNA encoding the sodium channel auxiliary subunit β4 (
Scn4b
) in 129P2 mice compared to FVB/N. This corresponded to low to undetectable β4 protein levels in 129P2 ventricular tissue, whereas abundant β4 protein was detected in FVB/N. Sodium current measurements in isolated myocytes from the 2 mouse strains indicated that sodium channel activation in myocytes from 129P2 mice occurred at more positive potentials compared to FVB/N. Using computer simulations, this difference in activation kinetics was predicted to explain the observed differences in conduction disease severity between the 2 strains. In conclusion, genetically determined differences in sodium current characteristics on the myocyte level modulate disease severity in cardiac sodium channelopathies. In particular, the sodium channel subunit β4 (
SCN4B
) may constitute a potential genetic modifier of conduction and cardiac sodium channel disease.
Hypoxic Preconditioning Enhances the Benefit of Cardiac Progenitor Cell Therapy for Treatment of Myocardial Infarction by Inducing CXCR4 Expression
Authors: Tang Yao Liang , Zhu Wuqiang , Cheng Min , Chen Lijuan , Zhang John , Sun Tao , Kishore Raj , Phillips M. Ian , Losordo Douglas W. , Qin Gangjian
Published: May 2009

Myocardial infarction rapidly depletes the endogenous cardiac progenitor cell pool, and the inefficient recruitment of exogenously administered progenitor cells limits the effectiveness of cardiac cell therapy. Recent reports indicate that interactions between the CXC chemokine stromal cell–derived factor 1 and its receptor CXC chemokine receptor 4 (CXCR4) critically mediate the ischemia-induced recruitment of bone marrow–derived circulating stem/progenitor cells, but the expression of CXCR4 in cardiac progenitor cells is very low. Here, we studied the influence of hypoxia on CXCR4 expression in cardiac progenitor cells, on the recruitment of intravenously administered cells to ischemic heart tissue, and on the preservation of heart function in a murine myocardial infarction model. We found that hypoxic preconditioning increased CXCR4 expression in CLK (cardiosphere-derived, Lin
−
c-kit
+
progenitor) cells and markedly augmented CLK cell migration (in vitro) and recruitment (in vivo) to the ischemic myocardium. Four weeks after surgically induced myocardial infarction, infarct size and heart function were significantly better in mice administered hypoxia-preconditioned CLK cells than in mice treated with cells cultured under normoxic conditions. Furthermore, these effects were largely abolished by the addition of a CXCR4 inhibitor, indicating that the benefits of hypoxic preconditioning are mediated by the stromal cell–derived factor 1/CXCR4 axis, and that therapies targeting this axis may enhance cardiac-progenitor cell–based regenerative therapy.
Prior Use of Statins Improves Outcome in Patients With Intracerebral Hemorrhage
Authors: Leker Ronen R. , Khoury Salim T. , Rafaeli Guy , Shwartz Roseline , Eichel Roni , Tanne David
Published: May 2009

Background and Purpose—

Intracerebral hemorrhage (ICH) is a deadly form of stroke. Pretreatment with statins exerts protective effects in patients with ischemic stroke, but their effects in patients with ICH remains unclear.

Methods—

The National Acute Stroke Israeli Surveys (NASIS) included all patients admitted with acute stroke to any of the 28 hospitals nationwide during February through March 2003 and March through April 2007. We compared stroke severity and outcomes of ICH patients who received statins before the index event with those who did not, using multivariable logistic regression models adjusting for the propensity to use statins before the event.

Results—

Among 3212 stroke patients, 312 had ICH and 89 of them were receiving statins at the time of the ICH. Patients on statins before ICH had lower baseline NIHSS scores, less systemic complications, higher proportions of good outcome (modified Rankin scale 0 to 3), lower death rates, and higher rates of discharge home or to a rehabilitation facility. On logistic regression analyses statin use before the event was associated with odds ratios of 0.46 for having a severe stroke defined as baseline NIHSS >15 (95% CI; 0.23 to 0.93), 2.97 for having good outcome (95% CI; 1.25 to 7.35) at discharge, and 0.25 for death or nursing facility disposition (95% CI; 0.09 to 0.63).

Conclusions—

Use of statins before ICH is associated with reduced mortality and neurological disability and with a higher chance for good outcome, suggesting that statins may be protective in the setting of ICH.
The Effect of Stereotype Threat on the Solving of Quantitative GRE Problems: A Mere Effort Interpretation
Authors: Jamieson Jeremy P. , Harkins Stephen G.
Published: May 2009

The mere effort account argues that stereotype threat motivates participants to want to perform well, which potentiates prepotent responses. If the prepotent response is correct, performance is facilitated. If incorrect and participants do not know, or lack the knowledge or time required for correction, performance is debilitated. The Graduate Record Examinations (GRE) quantitative test is made up of two problem types: (a) solve problems, which require the solution of an equation, and (b) comparison problems, which require the use of logic and estimation. Previous research shows that the prepotent tendency is to attempt to solve the equations. Consistent with mere effort predictions, Experiment 1 demonstrates that threatened participants perform better than controls on solve problems (prepotent response correct) but worse than controls on comparison problems (prepotent response incorrect). Experiment 2 shows that a simple instruction as to the correct solution approach eliminates the performance deficit on comparison problems.
Clinical outcome and tolerability of duloxetine in the treatment of major depressive disorder: a 12-week study with plasma levels
Authors: Volonteri LS , Colasanti A. , Cerveri G. , Fiorentini A. , De Gaspari IF , Mauri MC , Valli A. , Papa P. , Mencacci C.
Published: May 2009

Duloxetine (DLX) is a dual serotonin and norepinephrine reuptake inhibitor that has been recently approved for the treatment of major depressive disorder (MDD). However, little is known about the relationship between DLX plasma levels and clinical response. The aims of this open-label study were 1) to assess clinical outcome and tolerability of DLX by means of clinician and patient assessments and 2) to evaluate the value of plasma DLX levels as predictors of clinical response and tolerability. This was a naturalistic, open-label study of 45 outpatients affected with MDD (16 men and 29 women), who received DLX at doses of 30—120 mg/day and were evaluated at baseline (T0) and after 2, 4 and 12 weeks (T1—3). The assessments included the Hamilton Rating Scales for Depression (HRSD) and Anxiety (HRSA), Clinical Global Impression-Severity (CGI-S), Beck’s Depression Inventory (BDI) and a mood visual analogue scale (VAS). Compared with T0, there were significant improvements in HRSD at T1, T2 and T3 (P < 0.001), in HRSA, CGI-S and the self-administered BDI at T2 and T3 (P < 0.001), and in the VAS scores shown at T3 (P = 0.01). DLX treatment was safe and well tolerated. Plasma DLX levels at T2 ranged from 5 to 135 ng/mL (mean ± SD = 53.56 ± 39.45) and correlated almost significantly with the DLX dose (r = 0.35; P = 0.069). There was a significant curvilinear quadratic relationship between the improvement of HRSA scores and plasma DLX levels (R2 = 0.27; P = 0.02). The incidence of anxiety or irritability was associated with the highest plasma levels. Our findings suggest that monitoring plasma DLX levels may be helpful in predicting better treatment responses and tolerability. The present data seem to suggest an optimal anxiolytic efficacy of DLX at intermediate plasma levels.
Paradoxical enhancement of choice reaction time performance in patients with major depression
Authors: Chase HW , Michael A. , Bullmore ET , Sahakian BJ , Robbins TW
Published: May 2009

The Cued Reinforcement Reaction Time (CRRT) task is a choice reaction time task in which rewards (points) are available if the subject responds quickly enough and are signalled with a certain probability by stimuli. Reaction times (RTs) are faster following stimuli predicting reward with a high probability than with a low probability. This RT difference is sensitive to manipulations and individual differences in the serotonin (5-HT) system, but the CRRT task performance has not yet been examined in patients with depression. We observed that patients performed better on the task than controls, as evidenced by a greater points score, a greater likelihood of reaching their reinforcement threshold and fewer errors. RT variability was reduced in the patients. No group differences in the effect of the conditioned stimuli on RTs were observed. Accounts of these surprising data are discussed, considering possible effects of antidepressant medication or task-dependent differences in selective attention. Regardless of precise mechanism, the results do indicate that depressed patients are not invariably impaired in motivational paradigms and that their RT performance in certain situations can be superior to that of controls.
Fendiline-evoked [Ca2+]i rises and non-Ca2+-triggered cell death in human oral cancer cells
Authors: Huang CC , Huang CJ , Cheng JS , Liu SI , Chen IS , Tsai JY , Chou CT , Tseng PL , Jan CR
Published: May 2009

The effect of fendiline on cytosolic free Ca2+concentrations ([Ca2+]i) and proliferation has not been explored in human oral cancer cells. This study examined whether fendiline altered Ca2+levels and caused cell death in OC2 human oral cancer cells. [Ca2+]iand cell viability were measured using the fluorescent dyes fura-2 and WST-1, respectively. Fendiline at concentrations above 10 μM increased [Ca2+]iin a concentration-dependent manner. The Ca2+signal was reduced partly by removing extracellular Ca2+. The fendiline-induced Ca2+influx was sensitive to blockade of L-type Ca2+channel blockers. In Ca2+-free medium, after pretreatment with 50 μM fendiline, 1 μM thapsigargin (an endoplasmic reticulum Ca2+pump inhibitor)-induced [Ca2+]irises were inhibited; and conversely, thapsigargin pretreatment nearly abolished fendiline-induced [Ca2+]irises. Inhibition of phospholipase C with 2 μM U73122 did not change fendiline-induced [Ca2+]irises. At concentrations between 5 and 25 μM, fendiline killed cells in a concentration-dependent manner. The cytotoxic effect of 15 μM fendiline was not reversed by prechelating cytosolic Ca2+with BAPTA/AM. Collectively, in OC2 cells, fendiline induced [Ca2+]irises by causing Ca2+release from the endoplasmic reticulum and Ca2+influx from L-type Ca2+channels. Furthermore, fendiline-caused cytotoxicity was not via a preceding [Ca2+]irise.
Family Dissolution and Children's Criminal Careers
Authors: Skarðhamar Torbjørn
Published: May 2009

This study examines the relationship between family dissolution and children's crimes. The study uses a total population sample of a Norwegian birth cohort born in 1982 ( N = 49,975) and follows them through the crime statistics from ages 10 to 22 years, applying growth curve modelling. Both married and cohabiting parents are considered. There is a large and significant effect from family dissolution that persists after controlling for important economic confounders, even though these also show a high and significant effect. This suggests that, although some of the effect of parental break-up is explained by socioeconomic conditions, there also seems to be an independent and strong effect of family dissolution.
Weaving Color Lines: Race, Ethnicity, and the Work of Leadership in Social Change Organizations
Authors: Ospina Sonia , Su Celina
Published: May 2009

For social change organizations working to address intractable social problems throughou the US tackling race may not only be unavoidable, it may also represent away to fully engage stakeholders in social change work. We argue that illuminating the relationship between race and leaders hip can advance our understanding of how social change leadership happens in practice. We build upon scholarship that emphasizes the ways in which seemingly essentialist, intractable racial categories are actually mutable, and the simultaneous emergence of academic research calling attention to the constructed and collective dimensions of leadership. Using a constructionist lens to analyze narratives from 22 social change organizations and building six of these as in-depth cases, we document three distinct means of understanding race, explore how they help to do the work of leadership, and suggest ways in which they seem to move their work forward.
Developing Leaders in Cyber-space: The Paradoxical Possibilities of On-line Learning
Authors: Ladkin Donna , Case Peter , Gayá Wicks Patricia , Kinsella Keith
Published: May 2009

Whereas `distance learning' has often been seen as the poor relation of face-to- face educational encounters, this article suggests that paradoxically, this mode of delivery can offer significant advantages to those aiming to develop highly situated practices, such as leadership capability. In particular, the `distance' from the delivering educational establishment becomes `proximity' or an affordance in terms of where the learning is actually applied, and the constraints of the programme's structure enable greater freedom on the part of participants as they choose which aspects of theory they focus on. The argument presented here is based on research conducted to gain insight into participants' experience of a two-year Masters in Leadership Studies delivered primarily through on-line, web-based technology. We conclude that despite appearing to be a `transmission'-based learning intervention, the on-line mechanism fosters an experience similar to action learning in its engagement with participants' contexts, and also enables a more `constructivist' approach to learning about the practice, as well as the theory, of leadership.
Are the Best Leaders Both Transformational and Transactional? A Pattern-oriented Analysis
Authors: Gavan O'Shea Patrick , Foti Roseanne J. , Hauenstein Neil M. A. , Bycio Peter
Published: May 2009

Research exploring transformational and transactional leader behaviors has focused largely on bivarite relations among these behaviors and relevant criteria. This has limited the extent to which Bass's (1985) argument that optimally effective leaders engage in both types of behavior can be directly assessed. Pattern-oriented analyses were used here to discern which behavioral pattern was associated with the highest levels of subordinate satisfaction and commitment. In general, optimally effective leaders used a combination of transformational and contingent reward (e.g. exchange-based transactional leadership) behaviors, coupled with a low level of passive management-by-exception behavior (e.g. remaining uninvolved until problems emerge).
Ets1 and Ets2 are required for endothelial cell survival during embryonic angiogenesis
Authors: Wei Guo , Srinivasan Ruchika , Cantemir-Stone Carmen Z. , Sharma Sudarshana M. , Santhanam Ramasamy , Weinstein Michael , Muthusamy Natarajan , Man Albert K. , Oshima Robert G. , Leone Gustavo , Ostrowski Michael C.
Published: May 2009

The ras/Raf/Mek/Erk pathway plays a central role in coordinating endothelial cell activities during angiogenesis. Transcription factors Ets1 and Ets2 are targets of ras/Erk signaling pathways that have been implicated in endothelial cell function in vitro, but their precise role in vascular formation and function in vivo remains ill-defined. In this work, mutation of both Ets1 and Ets2 resulted in embryonic lethality at midgestation, with striking defects in vascular branching having been observed. The action of these factors was endothelial cell autonomous as demonstrated using Cre/loxP technology. Analysis of Ets1/Ets2 target genes in isolated embryonic endothelial cells demonstrated down-regulation of Mmp9, Bcl-XL, and cIAP2 in double mutants versus controls, and chromatin immunoprecipitation revealed that both Ets1 and Ets2 were loaded at target promoters. Consistent with these observations, endothelial cell apoptosis was significantly increased both in vivo and in vitro when both Ets1 and Ets2 were mutated. These results establish essential and overlapping functions for Ets1 and Ets2 in coordinating endothelial cell functions with survival during embryonic angiogenesis.
Frequency of vacA, cagA and babA2 virulence markers in Helicobacter pylori strains isolated from Mexican patients with chronic gastritis
Authors: Paniagua Gloria Luz , Monroy Eric , Rodríguez Raymundo , Arroniz Salvador , Rodríguez Cristina , Cortés José Luis , Camacho Ausencio , Negrete Erasmo , Vaca Sergio
Published: May 2009

Background

Helicobacter pylori has been strongly associated with chronic gastritis, peptic and duodenal ulcers, and it is a risk factor for gastric cancer. Three major virulence factors of H. pylori have been described: the vacuolating toxin (VacA), the cytotoxin-associated gene product (CagA) and the adhesion protein BabA2. Since considerable geographic diversity in the prevalence of H. pylori virulence factors has been reported, the aim of this work was to establish the H. pylori and vacA, cagA and babA2 gene status in 238 adult patients, from a marginal urban area of Mexico, with chronic gastritis.

Methods

H. pylori was identified in cultures of gastric biopsies by nested PCR. vacA and cagA genes were detected by multiplex PCR, whereas babA2 gene was identified by conventional PCR.

Results

H. pylori-positive biopsies were 143 (60.1%). All H. pylori strains were vacA
+; 39.2% were cagA
+; 13.3% were cagA
+
babA2
+ and 8.4% were babA2
+. Mexican strains examined possessed the vacA s1, m1 (43.4%), s1, m2 (24.5%), s2, m1 (20.3%) and s2, m2 (11.9%) genotypes.

Conclusion

These results show that the Mexican patients suffering chronic gastritis we have studied had a high incidence of infection by H. pylori. Forty four percent (63/143) of the H. pylori strains analyzed in this work may be considered as highly virulent since they possessed two or three of the virulence markers analyzed: vacA s1 cagA babA2 (9.8%, 14/143), vacA s1 babA2 (4.9%, 7/143), and vacA s1 cagA (29.4%, 42/143). However, a statistically significant correlation was not observed between vacAs1, cagA and babA2 virulence markers (χ2 test; P > 0.05).
Targeted Disruption of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Promotes Diet-Induced Hepatic Steatosis and Insulin Resistance
Authors: Xu Elaine , Dubois Marie-Julie , Leung Nelly , Charbonneau Alexandre , Turbide Claire , Avramoglu Rita Kohen , DeMarte Luisa , Elchebly Mounib , Streichert Thomas , Lévy Emile , Beauchemin Nicole , Marette André
Published: May 2009

Carcinoembryonic antigen-related cell adhesion molecule 1 (CC1) is a cell adhesion molecule within the Ig superfamily. The Tyr-phosphorylated isoform of CC1 (CC1-L) plays an important metabolic role in the regulation of hepatic insulin clearance. In this report, we show that CC1-deficient (Cc1−/−) mice are prone to hepatic steatosis, as revealed by significantly elevated hepatic triglyceride and both total and esterified cholesterol levels compared with age-matched wild-type controls. Cc1−/− mice were also predisposed to lipid-induced hepatic steatosis and dysfunction as indicated by their greater susceptibility to store lipids and express elevated levels of enzymatic markers of liver damage after chronic feeding of a high-fat diet. Hepatic steatosis in the Cc1−/− mice was linked to a significant increase in the expression of key lipogenic (fatty acid synthase, acetyl CoA carboxylase) and cholesterol synthetic (3-hydroxy-3-methylglutaryl-coenzyme A reductase) enzymes under the control of sterol regulatory element binding proteins-1c and -2 transcription factors. Cc1−/− mice also exhibited impaired insulin clearance, glucose intolerance, liver insulin resistance, and elevated hepatic expression of the key gluconeogenic transcriptional activators peroxisome proliferator-activated receptor-γ coactivator-1 and Forkhead box O1. Lack of CC1 also exacerbated both glucose intolerance and hepatic insulin resistance induced by high-fat feeding, but insulin clearance was not further deteriorated in the high-fat-fed Cc1−/− mice. In conclusion, our data indicate that CC1 is a key regulator of hepatic lipogenesis and that Cc1−/− mice are predisposed to liver steatosis, leading to hepatic insulin resistance and liver damage, particularly when chronically exposed to dietary fat.
Pioglitazone Acutely Reduces Insulin Secretion and Causes Metabolic Deceleration of the Pancreatic β-Cell at Submaximal Glucose Concentrations
Authors: Lamontagne Julien , Pepin Émilie , Peyot Marie-Line , Joly Érik , Ruderman Neil B. , Poitout Vincent , Madiraju S. R. Murthy , Nolan Christopher J. , Prentki Marc
Published: May 2009

Thiazolidinediones (TZDs) have beneficial effects on glucose homeostasis via enhancement of insulin sensitivity and preservation of β-cell function. How TZDs preserve β-cells is uncertain, but it might involve direct effects via both peroxisome proliferator-activated receptor-γ-dependent and -independent pathways. To gain insight into the independent pathway(s), we assessed the effects of short-term (≤90 min) exposure to pioglitazone (Pio) (10 to 50 μM) on glucose-induced insulin secretion (GIIS), AMP-activated protein kinase (AMPK) activation, and β-cell metabolism in INS 832/13 β-cells and rat islets. Pio caused a right shift in the dose-dependence of GIIS, such that insulin release was reduced at intermediate glucose but unaffected at either basal or maximal glucose concentrations. This was associated in INS 832/13 cells with alterations in energy metabolism, characterized by reduced glucose oxidation, mitochondrial membrane polarization, and ATP levels. Pio caused AMPK phosphorylation and its action on GIIS was reversed by the AMPK inhibitor compound C. Pio also reduced palmitate esterification into complex lipids and inhibited lipolysis. As for insulin secretion, the alterations in β-cell metabolic processes were mostly alleviated at elevated glucose. Similarly, the antidiabetic agents and AMPK activators metformin and berberine caused a right shift in the dose dependence of GIIS. In conclusion, Pio acutely reduces glucose oxidation, energy metabolism, and glycerolipid/fatty acid cycling of the β-cell at intermediate glucose concentrations. We suggest that AMPK activation and the metabolic deceleration of the β-cell caused by Pio contribute to its known effects to reduce hyperinsulinemia and preserve β-cell function and act as an antidiabetic agent.
In Vivo Interaction of Steroid Receptor Coactivator (SRC)-1 and the Activation Function-2 Domain of the Thyroid Hormone Receptor (TR) β in TRβ E457A Knock-In and SRC-1 Knockout mice
Authors: Alonso Manuela , Goodwin Charles , Liao XiaoHui , Ortiga-Carvalho Tania , Machado Danielle S. , Wondisford Fredric E. , Refetoff Samuel , Weiss Roy E.
Published: May 2009

The activation function-2 (AF-2) domain of the thyroid hormone (TH) receptor (TR)-β is a TH-dependent binding site for nuclear coactivators (NCoA), which modulate TH-dependent gene transcription. In contrast, the putative AF-1 domain is a TH-independent region interacting with NCoA. We determined the specificity of the AF-2 domain and NCoA interaction by evaluating thyroid function in mice with combined disruption of the AF-2 domain in TRβ, due to a point mutation (E457A), and deletion of one of the NCoAs, steroid receptor coactivator (SRC)-1. The E457A mutation was chosen because it abolishes NCoA recruitment in vitro while preserving normal TH binding and corepressor interactions resulting in resistance to TH. At baseline, disruption of SRC-1 in the homozygous knock-in (TRβE457A/E457A) mice worsened the degree of resistance to TH, resulting in increased serum T4 and TSH. During TH deprivation, disruption of AF-2 and SRC-1 resulted in a TSH rise 50% of what was seen when AF-2 alone was removed, suggesting that SRC-1 was interacting outside of the AF-2 domain. Therefore, 1) during TH deprivation, SRC-1 is necessary for activating the hypothalamic-pituitary-thyroid axis; 2) ligand-dependent repression of TSH requires an intact AF-2; and 3) SRC-1 may interact with the another region of the TRβ or the TRα to regulate TH action in the pituitary. This report demonstrates the dual interaction of NCoA in vivo: the TH-independent up-regulation possibly through another domain and TH-dependent down-regulation through the AF-2 domain.
What is the function of neuroglobin?
Authors: Burmester Thorsten , Hankeln Thomas
Published: May 2009

For a long time, haemoglobin and myoglobin had been assumed to represent the only globin types of vertebrates. In 2000, however, we discovered a third globin type by mining the genome sequence data. Based on a preferential expression in the nervous system, this globin is referred to as neuroglobin. Despite nine years of research, its function is still uncertain and a number of hypotheses have been put forward. Neuroglobin enhances cell viability under hypoxia and under various types of oxidative stress in transgenic systems, but does not appear to be strongly upregulated in response to stress. A close phylogenetic relationship with invertebrate nerve globins and its positive correlation with the oxidative metabolism and mitochondria suggest a role in O2 supply. In vitro studies and cell culture experiments imply that neuroglobin may detoxify reactive oxygen or nitric oxide. Still other studies propose neuroglobin as being part of a signalling chain that transmits the redox state of the cell or that inhibits apoptosis. Although some functions are more probable than others, we conclude that it is still too early to definitively decide what may be the physiological role(s) of neuroglobin in vertebrates. Nevertheless, there is no doubt that neuroglobin has an essential, conserved function and is beneficial to neurons.
A comparative study of the mechanical properties of Mytilid byssal threads
Authors: Pearce Trevor , LaBarbera Michael
Published: May 2009

Mytilid bivalves employ a set of threads (the byssus) to attach themselves to both hard and soft substrates. In this study, we measured the mechanical properties of byssal threads from two semi-infaunal mytilids (Geukensia demissa Dillwyn and Modiolus modiolus Linnaeus) and two epifaunal mytilids (Mytilus californianus Conrad and Mytilus edulis Linnaeus). We compared material properties with and without the assumption that changes of length and area during tensile testing are insignificant, demonstrating that previous researchers have overestimated extensibility values by 30% and may also have underestimated strength values. We detected significant differences in thread properties among tested mytilid species, contrary to previous findings. Threads from semi-infaunal species were significantly thinner than those from epifaunal species, perhaps to allow the production of a greater number of threads, which form a dense network within the substrate. Geukensia demissa threads were weaker than those of the other species, and had a significantly lower stiffness at failure. Modiolus modiolus threads were significantly stiffer than M. edulis threads but also significantly less extensible, suggesting a trade-off between stiffness and extensibility. The only thread property that did not show significant differences across species was toughness – even when byssal threads differ in strength or stiffness, they seem to absorb similar amounts of energy per unit volume prior to failure. This study reveals notable differences between the byssal thread properties of different mytilid bivalves and provides a reliable and thorough methodology for future comparative studies.
Dolphins maintain cognitive performance during 72 to 120 hours of continuous auditory vigilance
Authors: Ridgway Sam , Keogh Mandy , Carder Don , Finneran James , Kamolnick Tricia , Todd Mark , Goldblatt Allen
Published: May 2009

The present study reports the first use of a choice visual–vocal response time cognitive task, during 72 or 120 h of continuous auditory vigilance. Two adult bottlenose dolphins (Tursiops truncatus), NAY(male) and SAY (female), maintained a very high detection rate(91.1–98.7%) of random 1.5 s goal tones infrequently substituted in a background of frequent 0.5 s equal-amplitude tones over continuous 72 or 120 h sessions. In addition, a choice visual–vocal response time task (CVVRT)tested cognitive performance during night time sessions, when the dolphins would have ordinarily been resting or asleep as we had observed in previous studies. NAY and SAY detected a single-bar, posterior, vertical, green (S1g)or 3-bar, anterior, horizontal, red (S2r) LED light stimulus presented randomly to each eye. They responded with a different vocalization (whistle or pulse burst) to each stimulus (S1g or S2r) presented randomly to left and right eyes. The animals maintained high levels of goal tone detection without signs of sleep deprivation as indicated by behavior, blood indices or marked sleep rebound during 24 h of continuous post-experiment observation. Acoustic goal tone response time (AGTRT) overall did not change during the 72 h(F=0.528, P=0.655) or 120 h (F=0.384, P=0.816) sessions. Nor did CVVRT slow or degrade over the 72 h(F=4.188, P=0.104) or 120 h (F=2.298, P=0.119) AGTRT sessions.
Is the feeding and reproductive performance of the flea,Xenopsylla ramesis, affected by the gender of its rodent host,Meriones crassus?
Authors: Khokhlova Irina S. , Serobyan Vahan , Krasnov Boris R. , Degen A. Allan
Published: May 2009

Male-biased parasitism is commonly found in higher vertebrates and is most likely to be a result of higher mobility and lower immunocompetence of male hosts than female hosts. The latter would result in higher fitness of parasites exploiting males rather than females. To test this hypothesis, we investigated foraging and reproductive performance of fleas (Xenopsylla ramesis) parasitizing male and female Meriones crassus, a gerbilline rodent. We allowed fleas to feed on groom-restricted rodents and predicted that: (1) the size of a blood meal would be greater from a male than a female host and (2) female fleas will produce more eggs when exploiting a male than a female host. There was no effect of host gender on the mass-specific amount of blood consumed by a flea across eight days of feeding. However, on the first day fleas on a male rodent consumed significantly more blood than fleas on a female rodent. Thereafter, the amount of blood consumed from a male host tended to decrease whereas that from a female host tended to increase. A higher proportion of fleas satiated earlier than 60 min when they fed on male rather than on female hosts but this proportion decreased from the first to the last feeding event. Fleas produced significantly more eggs when they fed on male rather than on female hosts for days one to five of oviposition. We concluded that gender difference in immune defence is the mechanism behind male-biased parasitism.
Modelling electromechanical coupling in woven composites exhibiting damage
Authors: Bahei-El-Din Y A
Published: May 2009

Electroelastic woven composites are modelled with a transformation field analysis to determine the overall mechanical and electrical responses taking into consideration the progression of internal damage. The solution is found for a representative volume element of the composite material in terms of constant stress concentration factors, which quantify the local stresses caused by overall mechanical loads, and constant influence functions, which quantify the effect of local stress transformations such as those caused by electric fields. The effect of damage in limiting or eliminating local stresses is determined in terms of auxiliary transformation stresses. An example for a three-dimensional woven composite with piezoelectric filaments in the warp fibre direction shows that the computed electric displacement deviates from linearity with applied load at the onset of local damage. The indication of damage through electric displacement is more detectable when loading and electric measurement directions are not aligned. Local damage mechanisms show different effects on the magnitude of electric displacement. Damage within fibre bundles in the warp, weft, and z directions by sliding or splitting has the most significant effect on the electric displacement.
Medieval Romance and Wagner's Musical Narrative in the Ring
Authors: Harper-Scott J. P. E.
Published: May 2009

Wagner's engagement with medieval sources like the Nibelungenlied has generally been examined in relation to poetic style in his librettos. One of the defining structural features of his literary inspirations is the narrative interlace structure, which is common to literature, art, and even manuscript organization in the Middle Ages. In place of the classical Aristotelian unity of time, place, and action, the interlace design sets up a literary form based on sudden disjunctions, mysterious failures of explanation, and multiplicities of motive. These formal models propose radically different views of reality and the self: one suggests that human experience is shaped by a culmination that can already be known, the other more contingent, fractured, and paradoxically “modern.” Wagner's incorporation of the interlace design operates in the libretto and, more significantly and complexly, in the music. Wagner's structural and philosophical engagement with his medieval sources in the Ring may be elucidated via a combination of neo-Riemannian and modified Schenkerian analytical approaches and a sensitivity to Wagner's tendency to highlight the structural joints between his massive interlaced threads (rather than smoothly modulating, as the prevalent view suggests). The work is seen to have an existentialist, not an essentialist, view of human nature that provided an intellectual model for the artists and thinkers that grew up in Wagner's considerable intellectual shadow.
Mendelssohn in Nineteenth-Century American Hymnody
Authors: Mercer-Taylor Peter
Published: May 2009

The nineteenth century witnessed the rapid rise and gentle decline of an unprecedented vogue, particularly in the English-speaking world, for crafting hymn tunes from the work of Europe's most revered composers. Indeed, through the widely circulated publications of Lowell Mason and several like-minded American editors, it was in the form of hymnody that the European classical tradition reached a substantial part of the American population for the first time.

After setting forth broadly the historical underpinnings of such adaptations' dissemination, this study seeks to bring an unprecedented critical focus to the examination of a much-maligned repertoire through an exploration of the hymn tunes based on the work of one of its leading beneficiaries, Felix Mendelssohn. Gathered here are fifty-eight hymn tunes drawn from Mendelssohn's work, capturing what appears (based on a survey of 250 tune books and hymnals) to be the entry point of each particular melody into the American hymn repertoire. This body of music permits us not only to explore a multiplicity of approaches to the adaptation process itself, but to articulate a set of fundamental shifts that appear to have occurred in the genre as the nineteenth century wore on. From the late 1850s onward, we see not only a markedly heightened eagerness to adhere, in the adaptation process, to Mendelssohn's compositional will, but a pronounced move in the selection of melodic material away from the adventurous, catch-as-catch-can breadth of the mid-century publications toward tunes drawn from a more tightly circumscribed body of works that were coming to enjoy an established place in the concert repertoire at large.
Parallel Circulations
Authors: Mastropietro Christopher W. , Tourner Susan P.
Published: May 2009

Infants born with single-cardiac ventricle physiology frequently are treated preoperatively and postoperatively in neonatal intensive care units (NICUs), which requires neonatologists to be familiar with their unique anatomy, physiology, and consequent nonconventional principles of management. This case report reviews single-ventricle anatomy and physiology to explain appropriate interventions in the setting of cardiopulmonary arrest.
Rejection of Psychotropic Medicine and DSM–IV Nomenclature Produce Positive Outcomes for Gifted, Alienated, and Dually Diagnosed John Dewey Academy Students Who Were Self-Destructive: Part I
Authors: Bratter Thomas Edward
Published: May 2009

This is the first installment of a two-part article that describes the rejection of psychotropic medication and DSM–IV nomenclature at The John Dewey Academy (JDA), which has proven to be extremely effective for gifted, dually diagnosed, and unmotivated adolescents. One of the least studied phenomena that impact outcome are positive and negative expectations. These two psychotherapeutic principles maximize. Outcome results, when viewed from this perspective, certainly challenge the validity of the assumption that attributes pathology to a chemical imbalance, and in so doing ignores the roles of personal responsibility and choice (as opposed to compulsion). The second article will explicate the treatment guiding principles and effectiveness of compassionate confrontation. Critics challenge the philosophical and psychotherapeutic orientations that the JDA utilizes because they believe these constructs are simplistic and harsh, but cannot explain how superior success rates have been attained for a quarter of a century with a population of adolescents who rejected traditional therapeutic and teaching techniques.
Evaluation of dicloran's contribution to the mutagenic activity of Cristais river, Brazil, water samples
Authors: de Oliveira Danielle Palma , Sakagami Maureen , Warren Sarah , Kummrow Fábio , Umbuzeiro Gisela de Aragão
Published: May 2009

2,6-Dichloro-4-nitroaniline (dicloran) is a mutagenic aromatic amine used as an agricultural fungicide and in the synthesis of disperse dyes. It is a known mutagen (Salmonella/microsome assay) in strains TA98 and TA100. Dicloran was initially detected, but not quantified, in the Cristais River, Brazil. The objective of the present study was to estimate the contribution of dicloran to mutagenic activity in samples from this river. Dicloran was found in the raw water at 0.14 μg/L but not in the treated water. Comparison of mutagenic potencies in Salmonella strain YG1041 for dicloran and the river water sample indicated that dicloran contributed less than 0.1% of total mutagenic activity.
Comparison of two fecal egg recovery techniques and larval culture for cyathostomins in horses
Authors: Bello Thomas R. , Allen Tammy M.
Published: May 2009

Objective—To compare the McMaster and centrifugal flotation techniques and larval culture for recovery of cyathostomin (small strongyle) eggs from the feces of horses.

Sample Population—Fecal samples from 101 horses.

Procedures—In experiment I, homogenized fresh feces from a single horse were randomly subsampled by use of each technique for 10 replicates. In experiment II, samples from 43 horses that had no anthelmintic treatment were analyzed by use of McMaster, centrifugal flotation, and larval culture techniques. In experiment III, 57 horses were treated with an anthelmintic by owners, and fecal samples were analyzed as for experiment II.

Results—In experiment I, use of the McMaster technique recovered 72% of the eggs obtained by use of centrifugal flotation from paired subsamples. In experiment II, use of the McMaster technique recovered 81% of the eggs obtained by use of centrifugal flotation. Only cyathostomins resulted from individual larval cultures. In experiment III, 24 samples had negative results for all 3 tests, 18 samples had positive results only with larval cultures, and 15 samples had positive results of centrifugal flotation (only 5 of which had positive results via the McMaster technique).

Conclusions and Clinical Relevance—Centrifugal flotation consistently was superior to the McMaster technique, especially at low fecal egg numbers. The combination of centrifugal flotation and larval culture may provide the best accuracy for evaluation of anthelmintic efficacy.
Use of signal analysis of heart sounds and murmurs to assess severity of mitral valve regurgitation attributable to myxomatous mitral valve disease in dogs
Authors: Ljungvall Ingrid , Ahlstrom Christer , Höglund Katja , Hult Peter , Kvart Clarence , Borgarelli Michele , Ask Per , Häggström Jens
Published: May 2009

Objective—To investigate use of signal analysis of heart sounds and murmurs in assessing severity of mitral valve regurgitation (mitral regurgitation [MR]) in dogs with myxomatous mitral valve disease (MMVD).

Animals—77 client-owned dogs.

Procedures—Cardiac sounds were recorded from dogs evaluated by use of auscultatory and echocardiographic classification systems. Signal analysis techniques were developed to extract 7 sound variables (first frequency peak, murmur energy ratio, murmur duration > 200 Hz, sample entropy and first minimum of the auto mutual information function of the murmurs, and energy ratios of the first heart sound [S1] and second heart sound [S2]).

Results—Significant associations were detected between severity of MR and all sound variables, except the energy ratio of S1. An increase in severity of MR resulted in greater contribution of higher frequencies, increased signal irregularity, and decreased energy ratio of S2. The optimal combination of variables for distinguishing dogs with high-intensity murmurs from other dogs was energy ratio of S2 and murmur duration > 200 Hz (sensitivity, 79%; specificity, 71%) by use of the auscultatory classification. By use of the echocardiographic classification, corresponding variables were auto mutual information, first frequency peak, and energy ratio of S2 (sensitivity, 88%; specificity, 82%).

Conclusions and Clinical Relevance—Most of the investigated sound variables were significantly associated with severity of MR, which indicated a powerful diagnostic potential for monitoring MMVD. Signal analysis techniques could be valuable for clinicians when performing risk assessment or determining whether special care and more extensive examinations are required.
Effects of low-dose oligofructose treatment administered via nasogastric intubation on induction of laminitis and associated alterations in glucose and insulin dynamics in horses
Authors: Kalck Karen A. , Frank Nicholas , Elliott Sarah B. , Boston Raymond C.
Published: May 2009

Objective—To ascertain whether laminitis can be induced via administration of oligofructose (OF) at doses of 5.0 and 7.5 g/kg in horses and to assess glucose and insulin dynamics before and after treatment.

Animals—19 adult horses.

Procedures—Horses were fed OF (1.0 g/kg) mixed with oats for 6 days. Oligofructose at doses of 5.0 and 7.5 g/kg was then mixed with 4 L of water and administered (0 hours) to 8 (group A) and 4 (group B) horses, respectively, via nasogastric intubation; 8 horses received water alone. One horse in group A that did not develop laminitis was subsequently treated again and included in group B. Before and at intervals after treatment, resting plasma glucose and serum insulin concentrations were measured and frequently sampled IV glucose tolerance tests were performed. Area under the glucose curve (AUCg) and area under the insulin curve (AUCi) were calculated, and minimal model analyses were performed.

Results—3 of 8 horses in group A and all 4 horses in group B developed laminitis. Significant treatment-time effects were detected for resting plasma glucose concentrations and AUCg. Among horses in group A, mean AUCg values at 24 and 48 hours were 34% and 32% higher, respectively, than the mean value at 24 hours. Treatment groups did not differ significantly with respect to resting serum insulin concentration, AUCi, or minimal model analysis results.

Conclusions and Clinical Relevance—In horses, laminitis can be induced and glucose dynamics altered via nasogastric administration of 5.0 g of OF/kg. An alteration in insulin dynamics was not detected following treatment with OF.