bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrin-dependent translocation of LASP-1 to the cytoskeleton of activated platelets correlates with LASP-1 phosphorylation at tyrosine 171 by Src-kinase
Authors: Traenka Julia , Hauck Christof R , Lewandrowski Urs , Sickmann Albert , Gambaryan Stepan , Thalheimer Petra , Butt Elke
Published: July 2009

During platelet adhesion, the complex cytoskeletal structure is rearranged resulting in the formation of F-actin-based filopodia and lamellipodia. Stimulatory platelet signalling pathways include binding of integrin αIIbβ3 to fibrinogen followed by activation of protein tyrosine kinases (PTK) and phosphorylation of downstream signalling proteins. In this study, we demonstrate that the scaffolding and F-actin binding protein LASP-1 undergoes tyrosine phosphorylation in thrombin-stimulated human platelets. By means of specific inhibitors we identified Src-kinase as the primary enzyme phosphorylating LASP-1 in intact cells. These data were confirmed in platelet model cells (A5-CHO cells), constitutively expressing integrin αIIbβ3. Fibrinogen-mediated cell stimulation resulted in a similar tyrosine phosphorylation of transiently transfected LASP-1. Site directed mutagenesis identified tyrosine 171 as the Src-kinase phosphorylation site. Immunofluorescence microscopic analysis of these cells revealed a relocation of LASP-1 to focal contacts and the leading edge of the membrane upon fibrinogen activation and tyrosine 171 phosphorylation. This translocation was also seen in adherent platelets. Concomitant with adhesion, LASP-1 translocated from the cytosol along the arms of the pseudopodia into the leading lamellae of the spreading platelets, indicating a crucial role of the protein in platelet cytoskeleton rearrangement.
α1-acid glycoprotein (AGP)-induced platelet shape change involves the Rho/Rho kinase signalling pathway
Authors: Levander Louise , Påhlsson Peter , Grenegård Magnus , Gunnarsson Peter
Published: July 2009

α1-acid glycoprotein (AGP) is an acute-phase protein that contributes to inflammation processes.The role of AGP in platelet activation and thrombosis is, however, largely unknown.Therefore, we thoroughly investigated the effects of AGP on human platelets. Platelets were isolated from healthy volunteers and subsequently exposed to AGP. Platelet responses were monitored as change in light transmission, intracellular calcium concentration, light microscopy and protein phosphorylation by Western blot.We found that AGP induced platelet shape change independently of a second release of adenine nucleotides or thromboxane A2, and that effect was abolished by endotheliumderived platelet inhibitors such as nitric oxide (NO) and adenosine. Furthermore,AGP triggered a minor calcium response and a pronounced Rho/Rho-kinase-dependent increase in Thr696 phosphorylation of myosin phosphatase target subunit 1 (MYPT1). Moreover, the Rho/Rho-kinase inhibitor Y-27632 significantly decreased the AGP-induced shape change.The results also showed that the AGP-elicited shape change was antagonised by pretreatment with low doses of collagen and thrombospondin-1.Our results describe a novel mechanism by whichAGP stimulates platelet shape change via activation of the Rho/Rhokinase signalling pathway. Physiological important platelet inhibitors, such as NO, completely counterbalance the effect of AGP. Hence, the present study indicates that AGP directly contributes to platelet activation,which in turn might have an impact in physiological haemostasis and/or pathological thrombosis.
The recruitment of blood coagulation factor X into snake venom gland as a toxin
Authors: Kwong Shiyang , Woods Anthony E. , Mirtschin Peter J. , Ge Ruowen , Kini R.
Published: July 2009

Trocarin D is a prothrombin activator from the Tropidechis carinatus venom. It is a functional and structural homologue to mammalian blood coagulation factor Xa.Trocarin D is hypothesised to have evolved from its factor X counterpart (TrFX) through gene duplication and recruitment.The genes of trocarin D and TrFX have significant sequence identities, except for insertions/deletions in their intron 1 and promoter regions. In trocarin D intron 1 region, there are three insertions and two deletions. In trocarin D promoter region, there is a novel 264 bp insertion which has potential cis-elements.This insertion is termed as Venom Recruitment/Switch Element (VERSE) and is hypothesised to account for switching the low-level constitutive expression of factor X in the liver to the high-level inducible expression of trocarin D in the venom gland. To understand the role of VERSE in the trocarin D expression,its cis-elements were characterised by luciferase assays in mammalian cell lines as well as snake venom gland cells. The ability of VERSE to drive luciferase expression is comparable to that of the trocarin D promoter. The predicted cis-elements are important in promoting expression as their mutagenesis resulted in lower luciferase expression.VERSE minimal core promoter and three novel cis-elements (two up-regulatory and one suppressor elements) were identified using deletion/site-directed mutagenesis studies. VERSE is primarily responsible for the increase of trocarin D expression. The insertions/deletions within trocarin D intron 1 need to be characterised for their role in tissue-specific and inducible expression of trocarin D.
Mechanisms of platelet activation: Need for new strategies to protect against platelet-mediated atherothrombosis
Authors: Jennings Lisa
Published: July 2009

Platelets are central mediators of haemostasis at sites of vascular injury, but they also mediate pathologic thrombosis. Activated platelets stimulate thrombus formation in response to rupture of an atherosclerotic plaque or endothelial cell erosion, promoting atherothrombotic disease. They also interact with endothelial cells and leukocytes to promote inflammation, which contributes to atherosclerosis. Multiple pathways contribute to platelet activation, and current oral antiplatelet therapy with aspirin and a P2Y12 adenosine diphosphate (ADP) receptor antagonist target the thromboxane A2 and ADP pathways, respectively. Both can diminish activation by other factors, but the extent of their effects depends upon the agonist, agonist strength, and platelet reactivity status. Although these agents have demonstrated significant clinical benefit, residual morbidity and mortality remain high. Neither agent is effective in inhibiting thrombin, the most potent platelet activator. This lack of comprehensive inhibition of platelet function allows continued thrombus formation and exposes patients to risk for recurrent thrombotic events. Moreover, bleeding risk is a substantial limitation of antiplatelet therapy, because these agents target platelet activation pathways critical for both protective haemostasis and pathologic thrombosis. Novel antiplatelet therapies that provide more complete inhibition of platelet activation without increasing bleeding risk could considerably decrease residual risk for ischemic events. Inhibition of the protease-activated receptor (PAR)-1 platelet activation pathway stimulated by thrombin is a novel, emerging approach to achieve more comprehensive inhibition of platelet activation when used in combination with current oral antiplatelet agents. PAR-1 inhibition is not expected to increase bleeding risk, as this pathway does not interfere with haemostasis.
Risk stratification of patients with pulmonary embolism based on pulse rate and D-dimer concentration
Authors: van Bladel Esther R. , Schutgens Roger E. G. , Snijder Repke J. , Tromp Ellen A. M. , Prins Martin H. , Biesma Douwe H. , Agterof Mariette J.
Published: July 2009

To enable outpatient treatment of a selected group of patients with pulmonary embolism (PE), insight in the determinants of adverse clinical outcome is warranted. We have identified risk factors for serious adverse events (SAE) within the first 10 days of acute PE. We have retrospectively analysed data of 440 consecutive patients with acute PE. Collected data included age, gender, medical history, blood pressure, pulse rate and D-dimer concentration. The variables associated with SAE in the first 10 days in univariate analysis (p<0.15) have been included in a multivariate logistic regression model (backward conditional, p out>0.10). In 440 patients with acute PE, 20 SAEs occurred in a 10-day follow-up period. Pulse rate ≥100 beats per minute (bpm) (OR, 6.85; 95%CI 1.43–32.81) and D-dimer concentration ≥3,000 µg/ml (OR, 5.51; 95%CI 0.68–44.64) were significantly related to the SAEs. All SAEs were predicted by a pulse rate ≥100 bpm and/or a D-dimer concentration ≥3,000 µg/ml. Older age, gender, history of venous thromboembolism (VTE), heart failure, chronic obstructive pulmonary disease, cancer or a systolic blood pressure < 90 mm Hg had no significant influence on short term SAEs. Pulse rate and D-dimer concentration can be used to identify patients with acute PE, who are at risk for adverse clinical outcome during the first 10 days of hospitalisation. Outpatient treatment of PE-patients with a pulse rate ≥100 bpm and/or a D-dimer concentration ≥3,000 µg/ml has to be discouraged.
How much is too much? Interleukin-6 and its signalling in atherosclerosis
Authors: Schuett Harald , Luchtefeld Maren , Grothusen Christina , Grote Karsten , Schieffer Bernhard
Published: July 2009

The importance of inflammation as a driver of pathology is no longer confined to autoimmune and infectious diseases. In line with convincing experimental data as well as abundant clinical findings the current view of atherosclerosis points to inflammation as a critical regulator of atherosclerotic plaque formation and progression leading to the fatal clinical endpoints myocardial infarction, stroke or sudden cardiac death. The underlying mechanisms have been a matter of intense research during the last decades. In this regard, the interleukin-6 (IL-6) cytokines and their signalling events have been shown to contribute to both, atherosclerotic plaque development and plaque destabilisation via a variety of mechanisms. These involve the release of other pro-inflammatory cytokines, oxidation of lipoproteins by phospholipases, stimulation of acute phase protein secretion, the release of prothrombotic mediators, and the activation of matrix metalloproteinases. Moreover, the formation of reactive oxygen species generated by vascular enzyme systems may play a critical role in the regulation of IL-6 indicating a cross talk between vasoactive substances i.e. angiotensin II or adrenalin and pro-inflammatory cytokines such as IL-6. In this review we will summarise and discuss the underlying molecular and cellular mechanisms how IL-6 as an early and central regulator of inflammation contributes to atherosclerosis and how this knowledge can be integrated into the clinical context.
Muscarinic Receptor Upregulation in Patients With Myocardial Infarction
Authors: Mazzadi Alejandro N. , Pineau Julien , Costes Nicolas , Le Bars Didier , Bonnefoi Franck , Croisille Pierre , Porcher Raphaël , Chevalier Philippe
Published: July 2009

Background—

Despite the major role attributed to myocardial vagal activity in left ventricular arrhythmogenesis in chronic myocardial infarction, the impact of infarction on left ventricular muscarinic receptor density remains unknown.

Methods and Results—

Left ventricular muscarinic receptor density was measured in vivo by positron emission tomography using the specific antagonist [
11
C]methylquinuclidinyl benzilate ([
11
C]MQNB) in 11 patients 43�20 days after myocardial infarction and 9 healthy volunteers. The extent of myocardial damage was quantified by delayed contrast-enhanced MRI. Three short-axis slices from each subject were analyzed in matched positron emission tomography and MRI images. A 2-injection positron emission tomography protocol was used; [
11
C]MQNB time-activity curves were obtained in 6 regions per slice and fitted to a 3-compartment ligand-receptor model. Four classes of myocardial regions were considered: normal (in volunteers); remote, supplied by healthy or <70% diameter reduction arteries and without MRI signs of damage; potentially damaged, supplied by infarct-related or >70% diameter reduction arteries and without signs of damage; and damaged, with damage. The muscarinic receptor density in remote (67�30 pmol/mL tissue; n=86) and potentially damaged (71�30 pmol/mL tissue; n=42) regions of patients was higher than in normal regions of volunteers (32�17 pmol/mL tissue; n=156;
P
<0.001). The muscarinic receptor density in damaged regions (42�21 pmol/mL tissue; n=58) was reduced compared with remote and potentially damaged regions (
P
<0.001) but was not significantly different from normal regions in volunteers (
P
=0.093).

Conclusions—

Vagal control in patients with chronic myocardial infarction involves muscarinic receptor upregulation in remote nondamaged left ventricular regions. Our results suggest that the receptor density remains within normal values in myocardial regions containing damaged tissue.
Metabolic Syndrome and Periodontitis: Is Oxidative Stress a Common Link?
Authors: Bullon P. , Morillo J.M. , Ramirez-Tortosa M.C. , Quiles J.L. , Newman H.N. , Battino M.
Published: July 2009

A review of pathological mechanisms that can explain the relationship between periodontitis and cardiovascular disease (CVD) is necessary to improve the management of both conditions. Metabolic syndrome is a combination of obesity, hypertension, impaired glucose tolerance or diabetes, hyperinsulinemia, and dyslipidemia. All these have been examined in recent years in terms of their relationship to periodontitis. Reviewed data indicate an association between some of them (body mass index, high-density lipoprotein-cholesterol [HDL-C], triglycerides, high blood pressure, among others) and periodontitis. Oxidative stress may act as a potential common link to explain relationships between each component of metabolic syndrome and periodontitis. Both conditions show increased serum levels of products derived from oxidative damage, with a pro-inflammatory state likely influencing each other bidirectionally. Adipocytokines might modulate the oxidant/anti-oxidant balance in this relationship.
Localization of P. gingivalis in Preterm Delivery Placenta
Authors: Katz J. , Chegini N. , Shiverick K.T. , Lamont R.J.
Published: July 2009

Increasing evidence suggests an association between periodontal disease and adverse pregnancy outcomes. Although infection is considered as a risk factor for preterm delivery, the localization of oral bacteria or their antigens in chorioamnionitis placental tissue has never been demonstrated. This study was devised to test the hypothesis that periodontal pathogens may be present and affect human placenta in cases of chorioamnionitis. Using immunocytochemistry, we have identified the presence of Porphyromonas gingivalis antigens in placental tissues. The antigens were detected in the placental syncytiotrophoblasts, chorionic trophoblasts, decidual cells, and amniotic epithelial cells, as well as the vascular cells. There was a substantial increase in immunostaining intensity of the tissues sectioned from women with chorioamnionitis compared to those experiencing normalterm pregnancy, p < 0.019 (Mann‐Whitney test). These results suggest that P. gingivalis may commonly colonize placental tissue, and that the presence of the organism may contribute to preterm delivery.
Is Obesity an Oral Bacterial Disease?
Authors: Goodson J.M. , Groppo D. , Halem S. , Carpino E.
Published: July 2009

The world-wide explosion of overweight people has been called an epidemic. The inflammatory nature of obesity is widely recognized. Could it really be an epidemic involving an infectious agent? In this climate of concern over the increasing prevalence of overweight conditions in our society, we focus on the possible role of oral bacteria as a potential direct contributor to obesity. To investigate this possibility, we measured salivary bacterial populations of overweight women. Saliva was collected from 313 women with a body mass index between 27 and 32, and bacterial populations were measured by DNA probe analysis. Levels in this group were compared with data from a population of 232 healthy individuals from periodontal disease studies. The median percentage difference of 7 of the 40 bacterial species measured was greater than 2% in the saliva of overweight women. Classification tree analysis of salivary microbiological composition revealed that 98.4% of the overweight women could be identified by the presence of a single bacterial species ( Selenomonas noxia) at levels greater than 1.05% of the total salivary bacteria. Analysis of these data suggests that the composition of salivary bacteria changes in overweight women. It seems likely that these bacterial species could serve as biological indicators of a developing overweight condition. Of even greater interest, and the subject of future research, is the possibility that oral bacteria may participate in the pathology that leads to obesity.
Reflective Equilibrium in R & D Networks
Authors: van de Poel Ibo , Zwart Sjoerd D.
Published: July 2009

In this article, we develop an approach for the moral assessment of research and development (R & D) networks on the basis of the reflective equilibrium approach proposed by Rawls and Daniels. The reflective equilibrium approach aims at coherence between moral judgments, principles, and background theories. We use this approach because it takes seriously the moral judgments of the actors involved in R & D, whereas it also leaves room for critical reflection about these judgments. It is shown that two norms, namely reflective learning and openness and inclusiveness, which are used in the literature on policy and technological networks, contribute to achieving a justified overlapping consensus. We apply the approach to a case study about the development of an innovative sewage treatment technology and show how in this case the two norms are or could be instrumental in achieving a justified overlapping consensus on relevant moral issues.
`The One-Company Approach': Transnationalism in an Israeli—Palestinian Subsidiary of a Multinational Corporation
Authors: Ailon Galit , Kunda Gideon
Published: July 2009

This paper presents an ethnographic study of the Israeli—Palestinian subsidiary of a multinational hi-tech corporation. Critiquing the tendency of globalization theorists to conceptualize multinational corporations (MNCs) solely in terms of their impact on their external environment, this paper looks inward and examines the ideological and practical constituents of the transnational regime of consciousness as expressed through what management titles `the one-company approach'. We argue that this regime lays foundations for a transnational `imagined community' which does not rival the national one, but internalizes it, creating an arena of discretionary power for managers: deciding when to activate and when to suppress nationality in the global organizational universe. This study analyzes the relationship between transnationalism and nationalism inside the organization, and its implications for understanding MNCs' role in globalization.
Serendipity in Entrepreneurship
Authors: Dew Nicholas
Published: July 2009

This paper addresses the concept of serendipity in entrepreneurship, defined as search leading to unintended discovery. It conceptually delineates serendipity, showing how it is related to the entrepreneurship literature on prior knowledge and systematic search. The paper also discusses how serendipitous entrepreneurship relates to some aspects of evolutionary theory, socio-economic institutions, and social psychology. It is suggested that serendipity may be a quite prevalent feature of entrepreneurship and thus has implications for both research and practice.
Managing Expert Knowledge: Organizational Challenges and Managerial Futures for the UK Medical Profession
Authors: Waring Justin , Currie Graeme
Published: July 2009

The blurring of managerial and professional jurisdictions remains a significant area of organizational research. This process is often described as involving `re-stratification', the drawing of professional elites into bureaucratic roles; or `bureaucratization', the standardization of work operating procedures. We examine these processes further through considering how professional work is reordered through the application of knowledge management techniques, focusing in particular on the management of knowledge around clinical risk. We suggest attempts by hospital risk managers to manage medical knowledge towards organizational learning represent a significant challenge to clinical freedom, given the centrality of expert knowledge to professional autonomy. In considering this challenge, we are attentive to the idea that change occurs not through the top-down challenge of management, nor the bottom-up resistance of professionals, but through the dynamic mediation of these influences within a wider institutional context. Accordingly, we find that doctors respond to change through a number of situated responses that limit management control over knowledge and reinforce claims to medical autonomy. In extending professional jurisdiction for the management of knowledge, we show how professionals such as doctors can themselves become managerialized as they seek to stave off managerial encroachment. Rather than seeing professionals as being drawn into management roles or bureaucratic ways of working, we suggest that managerial techniques and jurisdictions are also strategically drawn into professional practice and identity.
The Prevalence of Middle Eastern Extremist Ideologies Among Some Canadian Offenders
Authors: Loza Wagdy
Published: July 2009

The Belief Diversity Scale (BDS) was administered to 89 male Canadian offenders of different religious backgrounds. The BDS is a 33-item, sixsubscale instrument designed to quantitatively measure the religious attitudes, beliefs, and ideologies of Middle Eastern extremists on risk areas described in the literature. Results indicated that the Muslim offenders scored much higher than and significantly different from both the Christian and atheist groups on the BDS. Results also suggested the prevalence of Middle Eastern extremist ideologies among the Muslim offenders involved in this study.
Differentials by Socioeconomic Status and Institutional Characteristics in Preventive Service Utilization by Older Persons in Costa Rica
Authors: Brenes-Camacho Gilbert , Rosero-Bixby Luis
Published: July 2009

Objective: The goals of this article are to assess the level of preventive service utilization by older persons in Costa Rica and to determine whether there are differentials in utilization across socioeconomic status (SES) and institutional characteristics. Method: Using data from the Costa Rican Study on Longevity and Healthy Aging (CRELES) project, a study of healthy aging in Costa Rica, the authors use self-reported information on preventive service utilization. The SES differentials are studied using logistic regressions. Results: Preventive services linked to cardiovascular disease prevention are frequently utilized; preventive services linked to cancer screening, vaccination, and sense impairments are not so widely used. Higher SES people are more likely to utilize most preventive services. Utilization rates among uninsured seniors are lower than among their insured peers. Home visits by community health workers are positively associated with higher utilization rates. Discussion: The SES disparities in preventive service utilization exist in Costa Rica, and institutional characteristics are positively associated with increasing utilization.
Acinar Cell Carcinoma With Prominent Intraductal Growth Pattern
Authors: Toll Adam D. , Mitchell Donald , Yeo Charles J. , Hruban Ralph H. , Witkiewicz Agnieszka K.
Published: July 2009

Acinar cell carcinoma of the pancreas is rare, accounting for less than 1% of carcinomas arising in the exocrine pancreas. Patients are typically between the fifth and seventh decade of life and show a 2:1 male predominance. Symptoms tend to be nonspecific, and approximately 50% of the patients have metastases at the time of presentation. There have been recent case reports of acinar cell carcinoma showing both intraductal and/or papillary patterns of growth that could potentially be mistaken for intraductal neoplasia. The cases reported up to date presented as solitary nodules. The authors describe the first case of acinar cell carcinoma with both intraductal and tubuloglandular growth diffusely involving the pancreas. In addition, the authors review the published cases reporting acinar cell carcinoma with intraductal and/or papillary growth patterns.
Finite Element Model for Hybrid Active-Passive Damping Analysis of Anisotropic Laminated Sandwich Structures
Authors: Araújo A.L. , Mota Soares C.M. , Mota Soares C.A.
Published: July 2009

In this article, we present a new finite element model for the analyzis of active sandwich laminated plates with a viscoelastic core and laminated anisotropic face layers, as well as piezoelectric sensor and actuator layers. The model is formulated using a mixed layerwise approach, by considering a higher order shear deformation theory to represent the displacement field of the viscoelastic core and a first-order shear deformation theory for the displacement field of the adjacent laminated anisotropic face layers and exterior piezoelectric layers. Control laws are implemented and the model is validated using reference solutions from the literature, and a benchmark application is proposed.
From reproduction to research
Authors: O'Riordan Kate , Haran Joan
Published: July 2009

This article provides an analysis of the relationships between IVF and therapeutic cloning, as they played out in the UK Human Fertilisation and Embryology Authority consultation of 2006: Donating Eggs for Research: Safeguarding Donors. We develop an account of current developments in IVF and cloning which foregrounds the role of mediation in structuring the discursive context in which they are constituted. We foreground the imperative of choice and the promise of cures as key features of this context. We also argue that the intercorporeal exchanges of IVF are materially restructured in relation to cloning research, despite their represented similitude in the consultation document. The discourse of choice in relation to reproductive technologies has become entrenched over the last twenty years. In relation to therapeutic cloning, it has been coupled with, and strengthened by, the discourse of cures. In examining relations between IVF and cloning with specific attention to both mediating imaginaries, and intercorporeal exchanges, we develop an analysis that displaces the rhetoric of choice and cures. This makes visible the limited subject positions available, and the limited possibilities for responding critically to the consultation. Identifying women as the gendered subjects of this consultation and placing intercorporeality at the centre of our analysis illuminates the interdependency of women undergoing IVF, cloning science and the governance of embryo research in the UK.
The Impact of the Spartathlon Ultramarathon Race on Athletes' Plantar Pressure Patterns
Authors: Karagounis Panagiotis , Prionas Giorgos , Armenis Elias , Tsiganos Georgios , Baltopoulos Panagiotis
Published: July 2009

More than 90% of injuries in runners are recorded in the lower extremity, equally affecting the regions of the knee, shank, and foot. Stress fractures are responsible for numerous running-related injuries. In the current study, the plantar pressure patterns of prerace, immediately postrace, and 24 hours after long-distance running in the Spartathlon were analyzed to compare foot loading in the respective conditions. Forty-six male participants of the Spartathlon ultramarathon were examined before, immediately after completion of the race, and 24 hours later with plantar pressure measurements during barefoot walking on a capacitive platform. The results revealed a significant increase in the peak pressure and impulse values in the forefoot areas and a decrease under the toes before and immediately after the race. On the contrary, no significant differences were found between the prerace and the 24-hour postrace values. The present findings indicate that the Spartathlon race leads to significant variations in foot-loading characteristics, especially in the peak pressure and impulse values under the forefoot and toe regions. Twenty-four-hour postrace data measurements reveal insignificant differences from the prerace statement, probably because of the restoration of local muscular activity.
Homing and invasiveness of MLL/ENL leukemic cells is regulated by MEF2C
Authors: Schwieger Maike , Schüler Andrea , Forster Martin , Engelmann Afra , Arnold Michael A. , Delwel Ruud , Valk Peter J. , Löhler Jürgen , Slany Robert K. , Olson Eric N. , Stocking Carol
Published: July 2009

Acute myelogenous leukemia is driven by leukemic stem cells (LSCs) generated by mutations that confer (or maintain) self-renewal potential coupled to an aberrant differentiation program. Using retroviral mutagenesis, we identified genes that generate LSCs in collaboration with genetic disruption of the gene encoding interferon response factor 8 (Irf8), which induces a myeloproliferation in vivo. Among the targeted genes, we identified Mef2c, encoding a MCM1-agamous-deficiens-serum response factor transcription factor, and confirmed that overexpression induced a myelomonocytic leukemia in cooperation with Irf8 deficiency. Strikingly, several of the genes identified in our screen have been reported to be up-regulated in the mixed-lineage leukemia (MLL) subtype. High MEF2C expression levels were confirmed in acute myelogenous leukemia patient samples with MLL gene disruptions, prompting an investigation of the causal interplay. Using a conditional mouse strain, we demonstrated that Mef2c deficiency does not impair the establishment or maintenance of LSCs generated in vitro by MLL/ENL fusion proteins; however, its loss led to compromised homing and invasiveness of the tumor cells. Mef2c-dependent targets included several genes encoding matrix metalloproteinases and chemokine ligands and receptors, providing a mechanistic link to increased homing and motility. Thus, MEF2C up-regulation may be responsible for the aggressive nature of this leukemia subtype.
Coordinated patterns of gene expressions for adult muscle build-up in transgenic mice expressing myostatin propeptide
Authors: Zhao Baoping , Li Eileena J , Wall Robert J , Yang Jinzeng
Published: July 2009

Background

Skeletal muscle growth and maintenance are essential for human health. One of the muscle regulatory genes, namely myostatin, a member of transforming growth factor-β, plays a dominant role in the genetic control of muscle mass. Myostatin is synthesized as a precursor protein, which generates the N-terminal propeptide and the C-terminal mature myostatin peptide by a post-translational cleavage event. Previously, transgenic over-expression of myostatin propeptide in skeletal muscle results in significant muscle growth in early stages of development. The objectives of present study were to further characterize muscle growth in later stages of life and to identify genes and their expression patterns that are responsible for adult muscle build-up by myostatin propeptide.

Results

Immunohistochemical staining with an antibody to the N-terminus indicates a high level of myostatin propeptide present in the muscles of transgenic mice while there were no apparent differences in myostatin protein distribution in the muscle fibers between the transgenic and wild-type mice. Main individual muscles increased by 76–152% in the transgenic mice over their wild-type littermate mice at 12 months of age. A large number of nuclei were localized in the central and basal lamina of the myofibers in the transgenic mice as the number of nuclei per fiber and 100 μm2 area was significantly higher in transgenic mice than wild-type mice. By systemic comparisons of global mRNA expression patterns between transgenic mice and wild-type littermates using microarray and qRT-PCR techniques, we have identified distinct gene expression patterns to support adult muscle build-up by myostatin propeptide, which are comprised of enhanced expressions of myogenic regulatory factors and extracelullar matrix components, and differentially down-regulated expressions of genes related to protein degradation and mitochondrial ATP synthesis.

Conclusion

The results present a coordinated pattern of gene expressions for reduced energy utilization during muscle build-up in adult stage. Enhanced muscle buildup by myostatin propeptide is sustained by reduced ATP synthesis as a result of a decreased activity of protein degradation. Myostatin propeptide may have a therapeutic application to the treatment of clinical muscle wasting problems by depressing myostatin activity.
Investigating the effects of climatic variables and reservoir on the incidence of hemorrhagic fever with renal syndrome in Huludao City, China: a 17-year data analysis based on structure equation model
Authors: Guan Peng , Huang Desheng , He Miao , Shen Tiefeng , Guo Junqiao , Zhou Baosen
Published: July 2009

Background

HFRS is a serious public health problem in China and the study on HFRS is important in China for its large population. The present study aimed to explore the impact of climatic variables and reservoir on the incidence of HFRS in Huludao City, an epidemic focus of the disease in northeastern China.

Methods

Structure Equation Model (SEM), a statistical technique for testing and estimating causal relationships, was conducted based on climatic variables, virus-carrying index among rodents, and incidence of HFRS in the city during the period 1990 to 2006. The linear structural relationships (LISREL) software (Scientific Software International, Lincolnwood, IL) was used to fit SEMs.

Results

Temperature, precipitation, relative humidity and virus-carrying index among rodents have shown positive correlations with the monthly incidence of HFRS, while air pressure had a negative correlation with the incidence. The best-fit SEM model fitted well with the data-based correlation matrix, P value was more than 0.56, root mean square error of approximation (RMSEA) equaled to 0, goodness-of-fit index (GFI) was more than 0.99.

Conclusion

Climate and reservoirs have affected the incidence of HFRS in Huludao City, located in northeastern China. Climate affects HFRS incidence mainly through the effect on reservoir in the study area. HFRS prevention and control should give more consideration to rodent control and climate variations.
Co-morbidities of vertiginous diseases
Authors: Warninghoff Jan C , Bayer Otmar , Ferrari Uta , Straube Andreas
Published: July 2009

Background

Co-morbidities of vertiginous diseases have so far not been investigated systematically. Thus, it is still unclear whether the different vertigo syndromes (e.g. benign paroxysmal positional vertigo (BPPV), Meniere's disease (MD), vestibular migraine and phobic vertigo (PPV)) have also different spectrums of co-morbidities.

Methods

All patients from a cohort of 131 participants were surveyed using a standardised questionnaire about the co-morbidities hypertension, diabetes mellitus, BMI (body mass index), migraine, other headache, and psychiatric diseases in general and the likelihood of a depression in particular.

Results

We noted hypertension in 29.0% of the cohort, diabetes mellitus in 6.1%, migraine in 8.4%, other headache in 32.1%, psychiatric diseases in 16.0%, overweight and obesity in 33.6% and 13.7% respectively, as well as a clinical indication for depression in 15.9%.

Conclusion

In general, we did not detect an increased prevalence of the co-morbidities diabetes mellitus, arterial hypertension, migraine, other headache and obesity compared to the general population. There was an increased prevalence of psychiatric co-morbidity in patients with PPV, and the prevalence of hypertension was elevated in patients with MD.
Mutations in many genes affect aggressive behavior in Drosophila melanogaster
Authors: Edwards Alexis C , Zwarts Liesbeth , Yamamoto Akihiko , Callaerts Patrick , Mackay Trudy FC
Published: July 2009

Background

Aggressive behavior in animals is important for survival and reproduction. Identifying the underlying genes and environmental contexts that affect aggressive behavior is important for understanding the evolutionary forces that maintain variation for aggressive behavior in natural populations, and to develop therapeutic interventions to modulate extreme levels of aggressive behavior in humans. While the role of neurotransmitters and a few other molecules in mediating and modulating levels of aggression is well established, it is likely that many additional genetic pathways remain undiscovered. Drosophila melanogaster has recently been established as an excellent model organism for studying the genetic basis of aggressive behavior. Here, we present the results of a screen of 170 Drosophila P-element insertional mutations for quantitative differences in aggressive behavior from their co-isogenic control line.

Results

We identified 59 mutations in 57 genes that affect aggressive behavior, none of which had been previously implicated to affect aggression. Thirty-two of these mutants exhibited increased aggression, while 27 lines were less aggressive than the control. Many of the genes affect the development and function of the nervous system, and are thus plausibly relevant to the execution of complex behaviors. Others affect basic cellular and metabolic processes, or are mutations in computationally predicted genes for which aggressive behavior is the first biological annotation. Most of the mutations had pleiotropic effects on other complex traits. We characterized nine of these mutations in greater detail by assessing transcript levels throughout development, morphological changes in the mushroom bodies, and restoration of control levels of aggression in revertant alleles. All of the P-element insertions affected the tagged genes, and had pleiotropic effects on brain morphology.

Conclusion

This study reveals that many more genes than previously suspected affect aggressive behavior, and that these genes have widespread pleiotropic effects. Given the conservation of aggressive behavior among different animal species, these are novel candidate genes for future study in other animals, including humans.
Development of an automated speech recognition interface for personal emergency response systems
Authors: Hamill Melinda , Young Vicky , Boger Jennifer , Mihailidis Alex
Published: July 2009

Background

Demands on long-term-care facilities are predicted to increase at an unprecedented rate as the baby boomer generation reaches retirement age. Aging-in-place (i.e. aging at home) is the desire of most seniors and is also a good option to reduce the burden on an over-stretched long-term-care system. Personal Emergency Response Systems (PERSs) help enable older adults to age-in-place by providing them with immediate access to emergency assistance. Traditionally they operate with push-button activators that connect the occupant via speaker-phone to a live emergency call-centre operator. If occupants do not wear the push button or cannot access the button, then the system is useless in the event of a fall or emergency. Additionally, a false alarm or failure to check-in at a regular interval will trigger a connection to a live operator, which can be unwanted and intrusive to the occupant. This paper describes the development and testing of an automated, hands-free, dialogue-based PERS prototype.

Methods

The prototype system was built using a ceiling mounted microphone array, an open-source automatic speech recognition engine, and a 'yes' and 'no' response dialog modelled after an existing call-centre protocol. Testing compared a single microphone versus a microphone array with nine adults in both noisy and quiet conditions. Dialogue testing was completed with four adults.

Results and discussion

The microphone array demonstrated improvement over the single microphone. In all cases, dialog testing resulted in the system reaching the correct decision about the kind of assistance the user was requesting. Further testing is required with elderly voices and under different noise conditions to ensure the appropriateness of the technology. Future developments include integration of the system with an emergency detection method as well as communication enhancement using features such as barge-in capability.

Conclusion

The use of an automated dialog-based PERS has the potential to provide users with more autonomy in decisions regarding their own health and more privacy in their own home.
A novel virus that infecting hypovirulent strain XG36-1 of plant fungal pathogen Sclerotinia sclerotiorum
Authors: Zhang Liyan , Fu Yanping , Xie Jiatao , Jiang Daohong , Li Guoqing , Yi Xianhong
Published: July 2009

Background

Sclerotinia sclerotiorumis a notorious plant fungal pathogen which spreads across the world. Hypovirulence is a phenomenon where the virulence of fungal pathogens is decreased, even lost, due to mycovirus infection. The potential of hypoviruses for biological control of the chestnut blight fungus (Cryphonectria parasitica) has attracted much interest, and has led to discovery of new hypovirulent strains in other fungi.

Results

A hypovirulent strain, strain XG36-1, was isolated from a typical lesion on the stem of rapeseed (Brassica napus) caused bySclerotinia sclerotiorum. Strain XG36-1 grew on PDA very slowly (average 2.5 ± 0.1 mm/d) with sectoring, and developed abnormal colony morphology with few sclerotia. Unlike health strains (such as wildtype strain XG-13), it was unable to induce lesions on detached leaves of rapeseed. Sclerotia of strain XG36-1 produced apothecia rarely. A sexual progeny test showed that the phenotypes of all 104 sexual progeny were not different from wildtype strain XG-13 which shows normal phenotype ofS. sclerotiorum, and protoplast regeneration tests showed that 25.5% of the regenerants of strain XG36-1 were recovered fully. Furthermore, the hypovirulence and its associated traits could be transmitted to XG36-1A34R, a hygromycin-resistance gene labelled sexual progeny of strain XG36-1, by hyphal anastomosis. Transmission electron microscope (TEM) observation showed that the cytoplasm of strain XG36-1 was destroyed and granulated; the membranes of nuclei and mitochondria were disintegrated; and mitochondrial cristae were cavitated. Viral particles (about 40 nm) in hyphae of strain XG36-1, but not in its sexual progeny and wildtype strain XG-13, could be observed with TEM, and several virus-like particles were uniquely enveloped by single layer membrane in the cells of strain XG36-1. Furthermore, the viral particles could be co-transmitted with the hypovirulence traits through hyphal anastomosis.

Conclusion

Hypovirulence and its associated traits of strain XG36-1 could be mediated by a fungal virus. Currently, we could not know the characteristic of this virus, but it likely represent a new type of mycovirus inS. sclerotiorum, and possibly in fungi.
Association between C-Reactive Protein and Adiposity in Women
Authors: Bochud Murielle , Marquant Fabienne , Marques-Vidal Pedro-Manuel , Vollenweider Peter , Beckmann Jacques S. , Mooser Vincent , Paccaud Fred , Rousson Valentin
Published: July 2009

Context: The link between C-reactive protein (CRP) and adiposity deserves to be further explored, considering the controversial diabetogenic role of CRP.

Objective: We explored the potential causal role of CRP on measures of adiposity.

Design: We used a Mendelian randomization approach with the CRP and LEPR genes as instrumental variables in a cross-sectional Caucasian population-based study comprising 2526 men and 2836 women. Adiposity was measured using body mass index (BMI), fat and lean mass estimated by bioelectrical impedance, and waist circumference.

Results: Log-transformed CRP explained by the rs7553007 single-nucleotide polymorphism tagging the CRP gene was significantly associated with BMI [regression coefficient: 1.22 (0.18; 2.25), P = 0.02] and fat mass [2.67 (0.65; 4.68), P = 0.01] but not with lean mass in women, whereas no association was found in men. Log-transformed CRP explained by the rs1805096 LEPR single-nucleotide polymorphism was also positively associated, although not significantly, with BMI or fat mass. The combined CRP-LEPR instrument explained 2.24 and 0.77% of CRP variance in women and men, respectively. Log-transformed CRP explained by this combined instrument was significantly associated with BMI [0.98 (0.32; 1.63), P = 0.004], fat mass [2.07 (0.79; 3.34), P = 0.001], and waist [2.09 (0.39; 3.78), P = 0.01] in women but not men.

Conclusion: Our data suggest that CRP is causally and positively related to BMI in women and that this is mainly due to fat mass. Results on the combined CRP-LEPR instrument suggest that leptin may play a role in the causal association between CRP and adiposity in women. Results in men were not significant.

Results in this study suggest that C-reactive protein is causally related to body mass index in women, and that this is mainly due to fat mass.
Masculinity in Video Games: The Gendered Gameplay of Silent Hill
Authors: Kirkland Ewan
Published: July 2009

This article explores construction and representation of masculinity in the “survival horror” video-game series Silent Hill. Noting the dominance of traditional male characters and masculine themes within the video-game medium, the Silent Hill franchise is seen as deviating from this assured, aggressive, and unexamined machismo. The series' protagonists are instead nondescript, flawed, domesticated men—unstable, angst-ridden, and unreliable in a manner that interrogates the dominant mode of masculine gameplay. The problematic nature of video-game interactivity and identity, the extent to which gameplay can exist independent of playable protagonists, and the gendering of video-game goals and objectives are considered. Despite conforming to certain masculine activities—fighting, collecting weaponry, exploring and dominating space—Silent Hill complicates such aspects through the game avatars' unremarkable abilities, limiting supplies, frantic combat styles, frustrating spatial progress, experiences of entrapment, and a pervading sense of helplessness, exemplified by the games' often deterministic linear structures. Overall, this article argues that the games encourage critical distance from the male game characters, the rescue missions they attempt and often fail, the monstrous images of femininity they imagine, and the voyeuristic practices in which they engage.
Reconstructing Shirley: Pedophilia and Interracial Romance in Hollywood's Age of Innocence
Authors: Osterweil Ara
Published: July 2009

In an era of motion picture history that forbade the representation of explicit adult sexuality and interracial romance, the appeal of Shirley Temple's innocent yet erotic persona was instrumentalized by the film industry as an important box office draw and powerful ideological weapon. This article examines Temple's pedophilic persona, concentrating on several plantation films she made with Bill “Bojangles” Robinson between 1935 and 1936, including The Little Colonel, The Littlest Rebel, and Dimples. By analyzing the complex discourses of pedophilia and miscegenation that coalesce in these films, Osterweil reads these texts as attempts to reconcile the trauma of interracial desire as represented in D. W. Griffith's Birth of a Nation (1915). Yet while these films superimpose their own utopian fantasies of interracial, intergenerational romance over the vision of racial violence “written in lighting” by Griffith, they also systematically engage in, and attempt to disguise, their own insidious racial exploitation, both onscreen and offscreen. Constructed to incite and assuage anxieties about the transgression of boundaries between black and white, male and female, and adult and child, Temple's adorable characters both naturalized and eroticized the racial exploitation these films celebrated. For in her performances of complex racial, sexual, and gendered masquerades, Temple's characters engaged in forms of passing that were crucial to the domestication of blackness during this period.