bluuebunny/crossref_metadata_2025 huggingface dataset:
Assimilation and Contrast in a Test of the Hostile Media Effect
Authors: Gunther Albert C. , Miller Nicole , Liebhart Janice L.
Published: October 2009

Recent empirical research has vividly demonstrated the hostile media effect—the tendency for individuals highly involved in a controversial issue to see media coverage of that issue as hostile to their own point of view. This type of contrast bias—along with its assimilation counterpart—is hypothesized to stem from preexisting partisan attitudes coupled with other explanatory factors, including perceived reach of the message and characteristics of the source. To test these predictions, we recruited partisan respondents who were either Native American or sympathetic to native issues. Participants ( N = 152) read information, varying in apparent circulation (low, medium and high reach) and source (friendly vs. not friendly) characteristics, on the issue of genetically modified wild rice, a controversial topic for native people in the upper Midwest. Variations in reach produced a linear trend in judgments of bias in the predicted direction. However, overall evaluations tended toward assimilation rather than contrast effects, and two distinct dimensions of partisanship produced surprising and provocative results.
Does Family Process Mediate the Effect of Religiosity On Adolescent Deviance?
Authors: Pickering Lloyd E. , Vazsonyi Alexander T.
Published: October 2009

A considerable amount of research has been conducted on the nature of the relationship between both religiosity and family process with deviance. There are few studies, however, that investigate the interplay among religiosity, family process, and deviance. The current study sought to examine whether family process mediates the relationship between religiosity (conceptualized as ritualistic participation and relational practice) and deviance. High school students ( N = 865) responded to survey questions dealing with religiosity (two scales), family process (six scales for both mothers and fathers), and deviance (seven subscales and a total deviance scale). A structural equation modeling (SEM) analytic approach was used. Results indicated that family process did not mediate the relationship between religiosity and deviance. Relational practice was found to be a more robust predictor of deviant behavior than ritualistic participation. Future research in this area should seek to improve methods of data collection (e.g., multimethod) and to develop better scalar measures of religiosity.
Ethnic Variations in the Connection Between Work-Induced Family Separation and Turnover Intent
Authors: Behnke Andrew O. , MacDermid Shelley M. , Anderson James C. , Weiss Howard M.
Published: October 2009

Using conservation of resources theory, this study examines the role of resources in the relationship between work-induced family separation and workers’ intentions to leave their employment and how these relationships vary across ethnic groups. Analyses of a large representative sample of military members reveal that family separation is significantly related to intent to leave the military and that this relationship is partially mediated by resources for all ethnic groups. Work- and family-related resources are the most strongly related to both separation and turnover for all ethnic groups, but significant ethnic variations are found for most paths in the model. Results are discussed in terms of applications inside and outside the military and potential implications for conservation of resources theory.
Halogen-free Flame Retardants that Outperform Halogenated Counterparts in Glass Fiber Reinforced Polyamides
Authors: Isitman Nihat Ali , Gunduz Huseyin Ozgur , Kaynak Cevdet
Published: October 2009

Flammability, fire performance, and thermal stability of short glass fiber reinforced polyamide-6 and polyamide-66 containing halogenated and halogen-free flame retardants (FRs) were compared. Flammabilities were assessed by limiting oxygen index tests and UL94 classifications. Fire behavior was evaluated by mass loss cone calorimetry, a bench-scale tool, to assess fire performance of materials. Halogen-free, phosphorus-based FRs were shown to perform superior to halogenated counterparts on the basis of important fire properties, peak heat release rate, time to ignition, and fire growth index. Moreover, thermal stabilities were maintained at an acceptable level as a clear advantage of halogen-free FRs.
Climates of risk: A field analysis of global climate change in US media discourse, 1997-2004
Authors: Sonnett John
Published: October 2009

How are industry and environmentalist discourses of climate risk related to dominant scientific and political discourses? This study operationalizes Bourdieu’s concept of symbolic capital in order to map dimensions of risk description and prescription onto a journalistic field of industry, environmentalist, scientific, and political media. Results show that conventional definitions of risk mirror an opposition between scientific and political discourses. Prescriptions for action on risk are partly autonomous from definitions however. Environmentalist and scientific media feature more proactive discourse, and industry and political media feature more reactive discourse. Implications for future research on climate risk and relational studies of media discourse are discussed.
“… a certain amount of engineering involved”: Constructing the public in participatory governance arrangements
Authors: Braun Kathrin , Schultz Susanne
Published: October 2009

This paper argues that it is time for public understanding of science to develop a critical inventory of the forms, formats and methods of public participation and their respective implications and ambiguities. It highlights the need for analysing not only the limitations and deficiencies of participatory arrangements but also their constructive dimension, in particular the construction of the subject of participation. Looking into participatory governance arrangements in the issue area of genetic testing in Germany and the UK the paper presents a typology of formats according to the way the respective public is constructed and identifies four major constructions of publics: the general public, the pure public, the affected public and the partisan public. Each of these enables certain speaking positions while foreclosing others. The study shows that the main purposes of participatory arrangements in this issue area are knowledge production and education rather than political deliberation and decision-making.
From enabling technology to applications: The evolution of risk perceptions about nanotechnology
Authors: Cacciatore Michael A. , Scheufele Dietram A. , Corley Elizabeth A.
Published: October 2009

Public opinion research on nanotechnology has primarily focused on judgments of abstract risks and benefits, rather than attitudes toward specific applications. This approach will be less useful as nanotechnology morphs from a scientific breakthrough into an enabling technology whose impacts on people’s lives come in the form of concrete applications in specific areas. This study examines the mental connections or associations US citizens have with nanotechnology (e.g. the extent to which people associate nanotechnology with the medical field, the military, consumer products, etc.), and how these associations moderate the influences of risk and benefit perceptions on attitudes toward nanotechnology. Our results suggest that the assumption that risk perceptions shape overall attitudes toward emerging technologies is simplistic. Rather, individuals who associate nanotech with particular areas of application, such as the medical field, take risk perceptions much more into account when forming attitudes than respondents who do not make these mental connections.
Transnational Cultural Ecologies: Evolving Challenges for Nurses in Canada
Authors: Isaacs Sandra
Published: October 2009

Canada is experiencing an evolving cultural ecology as new arrivals of immigrants now realize opportunities for sustaining familiar ties with home countries through advancing technologies and travel. Those arriving will have diverse experiences and preferences, many with opportunities for meeting their health needs elsewhere. For those less privileged, options for health care and health enabling resources are more limited as existing health systems continue to give preference to a dominant culture based on a European heritage—even though, progressively, Canadian society becomes more diverse in its cultural makeup. We as nurses and others engaged in health care systems need to consider our own acculturation processes as we adapt to the changes happening in our society. Systemic approaches to cultural competency in health care need to be considered that enable nurses and other health care providers to be adaptive and resilient in a transnational world.
The Journey Between Western and Indigenous Research Paradigms
Authors: Getty Grace A.
Published: October 2009

This article is an account of the author’s journey as a White researcher preparing to do a community-based participatory action research study with Mi’kmaq men. In this article, a postcolonial approach is examined, interrogating the utility of this theoretical approach in research with Aboriginal people. Next, the foundations of an Indigenous worldview is identified, followed by a debate about the strengths and weaknesses of a critical social theory approach in light of an Indigenous worldview. Finally, lessons about an Indigenous research paradigm including the benefits of using a theoretical approach based on an Indigenous knowledge system are identified.
The Paradox of Progress: Translating Evan Stark’s Coercive Control Into Legal Doctrine for Abused Women
Authors: Hanna Cheryl
Published: October 2009

This article examines Evan Stark’s model of coercive control and what this paradigm shift might mean for the law. Coercive control can help redefine both criminal offenses involving domestic violence and defenses available to women who kill their abusers. This redefinition would shift the law away from incident-based violence and toward a more comprehensive and accurate paradigm that accounts for the deprivation of a woman’s autonomy within the context of an abusive relationship. Such a change would likely provide more effective state intervention into what were once considered private relationships. Yet, this approach may also have some unintended consequences, including refocusing the law on a victim’s mental state and complicity in her own abuse rather than on the harm caused by abusive men. Thus, although the law should more fully account for coercive control, lawyers must be cautiously optimistic in implementing Stark’s proposed reforms.
Standing on One’s Own Feet: New Graduate Nurses’ Home Health Care Challenges and Work Experiences Study
Authors: Sneltvedt Torild , Odland Liv-Helen , Sørlie Venke
Published: October 2009

Interest is growing for information on recently qualified nurses’ initial meeting with working life. This study aims to shed light on recently qualified nurses’ experience working in home health care. The authors chose to design the study using a phenomenological hermeneutical approach with narrative interviews and text analysis. The respondents consist of a group of four recently qualified nurses. The results show that they are surprised by the many competence requirements and expectations, that they experience feeling alone, and that they also bear large responsibility. At the same time, they enjoy their work, in which they seek to influence the working conditions for their professional practice. They do experience the anxiety of not being able to cope with the challenge of nursing practice, but they are not marked by the shock of reality.
Review Series: What goes around, comes around: childhood influences on later lung health?: Relationship between environmental exposures in children and adult lung disease: The case for outdoor exposures
Authors: Soto-Martinez Manuel , Sly Peter D
Published: October 2009

There is a growing understanding that chronic respiratory diseases in adults have their origins in early life. Adverse environmental exposures occurring in vulnerable periods during lung growth and development in the fetal period and in early childhood that alter lung structure and limit the growth in lung function may have lifelong consequences. Evidence is increasing that exposure to the ambient environment, including air pollutants, persistent toxic substances, water pollutants and respiratory viral infections, can inhibit lung function growth and predispose to chronic non-malignant lung diseases. These exposures generally interact with a genetic predisposition, and gene—environment interactions and epigenetic phenomena are attracting considerable study. An understanding of how ambient exposures impact on normal lung growth and development will aid in understanding of how chronic respiratory diseases of adults develop and may lead to new preventative strategies.
Targeting Prosody: A Case Study of an Adolescent
Authors: Bellon-Harn Monica L.
Published: October 2009

Currently, there are few published treatment studies to address prosody in clinical populations. Developing treatment protocols is challenging due to the considerable degree of heterogeneity across individuals with prosodic disturbances and the multiple aspects of prosody, voice, speech, and language that can be affected. The purpose of this article is to describe the clinical management of prosody and outcomes in an adolescent who exhibits atypical prosody, residual segmental speech errors, morphosyntactic errors, and social communicative difficulties. An explicit approach using meta-awareness and discrimination strategies was used. Positive outcomes in some targeted behaviors were noted, whereas other behaviors did not change. Outcomes are discussed relative to the treatment approach.
Ultrasound of Focal Salivary Gland Lesions
Authors: Chowdhury Rajat , Pratt Hazel A , Dewbury Keith C , Rutherford Elizabeth E
Published: October 2009

Ultrasound is a sensitive tool for assessing focal salivary gland lesions and is the initial imaging modality of choice for investigating such conditions. Whilst certain lesions have very characteristic ultrasound appearances, many hyperechoic lesions have non-specific imaging features resulting in diagnostic uncertainty based on imaging alone. Here we review the appearances of these lesions on ultrasound and highlight the importance of proceeding to ultrasound-guided fine-needle aspiration for cytology or core biopsy to reach a definitive diagnosis.
Development of a Primary Testicular Tumour during Surveillance for Testicular Microlithiasis
Authors: Amaechi Iheoma , Khan Mohammed Z , Sidhu Paul S
Published: October 2009

We describe a case of the development of a testicular tumour in a patient with unilateral limited testicular microlithiasis after five years on a follow-up surveillance program. We discuss the risk factors for the development of a testicular tumour, review the literature, and suggest a management strategy for follow-up of patients with testicular microlithiasis.
The Parent’s Experience of Clubfoot Diagnosis Across the UK
Authors: Shelton Ros S , Banton Sue
Published: October 2009

This study presents a UK-wide snapshot of the experiences of families of children with idiopathic congenital talipes equinovarus (CTEV). 111 families with 112 affected children completed a questionnaire containing open and closed questions about demographic data, diagnosis, treatment, and support, from 50 of 72 UK counties. All children were born between July 2002 and June 2007. CTEV was diagnosed prenatally in 81 (72%) infants. Most families (73, 66%) felt that the prenatal care they received could have been improved. The most common complaint (38 families) was lack of information at the time of diagnosis. The most common reaction (50 families) was shock or distress. A comparison between modes of information delivery revealed that prenatal consultations and leaflets were commonly provided but that families preferred prenatal consultations, the internet, and a DVD. Almost all families (102 out of 111, 92%) who responded said they sought information independently. Most families (84%) used the internet and some were distressed by what they found. We conclude that the experience of families when a child is diagnosed with CTEV during the 20-week prenatal ultrasound scan is less stressful when good quality information is provided or when families are signposted to reputable sources.
Colony-Stimulating Factor-1 (CSF-1) Directly Inhibits Receptor Activator of Nuclear Factor-κB Ligand (RANKL) Expression by Osteoblasts
Authors: Wittrant Y. , Gorin Y. , Mohan S. , Wagner B. , Abboud-Werner S. L.
Published: October 2009

Colony-stimulating factor-1 (CSF-1), released by osteoblasts, stimulates the proliferation of osteoclast progenitors via the c-fms receptor (CSF-1R) and, in combination with receptor activator of nuclear factor-κB ligand (RANKL), leads to the formation of mature osteoclasts. Whether the CSF-1R is expressed by osteoblasts and mediates specific biological effects in osteoblasts has not been explored. Wild-type primary calvaria osteoblasts (OB) were analyzed for CSF-1R expression (RT-PCR and Western blot) and functionality (immunocomplex kinase assay). OB were serum starved for 24 h, and the effect of CSF-1 (0–100 ng/ml) on OB biological activities was determined at 48 h. In wild-type mouse bone marrow cultures, CSF-1 was tested for its effect on RANKL mRNA and osteoclast formation. Because ROS influence osteoblast RANKL expression, studies analyzed the effect of CSF-1 on reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and Nox1 and Nox4 proteins. Results indicate that OB express CSF-1R mRNA and protein and that CSF-1R could be phosphorylated in the presence of CSF-1. In osteoblasts, CSF-1 decreased RANKL mRNA in a dose- and time-dependent manner. Incubation of bone marrow cultures with CSF-1 resulted in a significant decline in tartrate-resistant acid phosphatase (TRACP) activity and CTR expression. RANKL-decreased expression by CSF-1 was correlated with a decrease of NADPH oxidase activity as well as Nox1 and Nox4 protein levels. These findings provide the first evidence that osteoblasts express CSF-1R and are a target for CSF-1 ligand. CSF-1-mediated inhibition of RANKL expression on osteoblasts may provide an important mechanism for coupling bone formation/resorption and preventing excessive osteoclastogenesis during normal skeletal growth.
Cathepsin D Is the Primary Protease for the Generation of Adenohypophyseal Vasoinhibins: Cleavage Occurs within the Prolactin Secretory Granules
Authors: Cruz-Soto Martha E. , Cosío Gabriela , Jeziorski Michael C. , Vargas-Barroso Víctor , Aguilar Manuel B. , Cárabez Alfonso , Berger Peter , Saftig Paul , Arnold Edith , Thebault Stéphanie , Martínez de la Escalera Gonzalo , Clapp Carmen
Published: October 2009

Vasoinhibins are a family of N-terminal prolactin (PRL) fragments that inhibit blood vessel growth, dilation, permeability, and survival. The aspartyl endoprotease cathepsin D is active at acidic pH and can cleave rat PRL to generate vasoinhibins. We investigated whether and where vasoinhibins could be generated by cathepsin D in the adenohypophysis of rats and mice and whether their production could be gender dependent. Vasoinhibins were detected in primary cultures of rat adenohypophyseal cells by Western blot with antibodies directed against the N terminus of PRL but not the C terminus. Ovariectomized, estrogen-treated females show greater levels of adenohypophyseal vasoinhibins than males. Peptide sequencing analysis revealed that the cleaved form of PRL in rat adenohypophyseal extracts contains the PRL N terminus and a second N terminus starting at Ser149, the reported cleavage site of cathepsin D in rat PRL. In addition, cathepsin D inhibition by pepstatin A reduced vasoinhibin levels in rat adenohypophyseal cell cultures. Confocal and electron microscopy showed the colocalization of cathepsin D and PRL within rat adenohypophyseal cells and secretory granules, and a subcellular fraction of rat adenohypophysis enriched in secretory granules contained cathepsin D activity able to generate vasoinhibins from PRL. Of note, vasoinhibins were absent in the adenohypophysis of mice lacking the cathepsin D gene but not in wild-type mice. These findings show that cathepsin D is the main protease responsible for the generation of adenohypophyseal vasoinhibins and that its action can take place within the secretory granules of lactotrophs.
Local Secretion of Urocortin 1 Promotes Microvascular Permeability during Lipopolysaccharide-Induced Inflammation
Authors: Cureton Elizabeth L. , Ereso Alexander Q. , Victorino Gregory P. , Curran Brian , Poole Daniel P. , Liao Min , Harken Alden H. , Bhargava Aditi
Published: October 2009

Urocortin 1 (Ucn1) is a neuropeptide that regulates vascular tone and is implicated in both the vascular and immune cell-mediated responses to inflammation. The role of Ucn1 in regulating microvascular permeability has not been determined. We hypothesized that local Ucn1 release promotes microvascular permeability and that this effect augments the local gastrointestinal vascular response to lipopolysaccharide (LPS)-induced systemic inflammation. We measured hydraulic (Lp) and macromolecule permeability in mesenteric venules. We show that a continuous infusion of 10−7m Ucn1 in a postcapillary venule increased Lp 2-fold over baseline, as did LPS-induced inflammation. However, simultaneous infusion of Ucn1 and LPS markedly increased Lp by 7-fold. After local knockdown of Ucn1 using RNA interference, infusion of Ucn1 with LPS resulted in return to 2-fold increase, confirming that Ucn1 synergistically augments hydraulic permeability during inflammation. LPS and Ucn1 treatment also resulted in increased numbers of interstitial microspheres, which colocalized with CD31+ immune cells. Ucn1 activity is mediated through two receptor subtypes, CRH-R1 and CRH-R2. CRH-R1 receptor blockade exacerbated, whereas CRH-R2 receptor blockade decreased the LPS-induced increase in Lp. Finally, treatment with the c-JUN N-terminal kinase (JNK) antagonist SP600125 during infusion of LPS, but not Ucn1, decreased Lp. These findings suggest that Ucn1 increases microvascular permeability and acts synergistically with LPS to increase fluid and macromolecule losses during inflammation. Knockdown of endogenous Ucn1 during inflammation attenuates synergistic increases in Lp. Ucn1’s effect on Lp is partially mediated by the CRH-R2 receptor and acts independently of the c-JUN N-terminal kinase signal transduction pathway.
The Rho Guanosine 5′-Triphosphatase, Cell Division Cycle 42, Is Required for Insulin-Induced Actin Remodeling and Glucagon-Like Peptide-1 Secretion in the Intestinal Endocrine L Cell
Authors: Lim Gareth E. , Xu Molie , Sun Jane , Jin Tianru , Brubaker Patricia L.
Published: October 2009

Rho GTPases, such as cell division cycle 42 (Cdc42) and ras-related C3 botulinum toxin substrate 1 (Rac1), have been identified as regulators of F-actin dynamics and hormone release from endocrine cells; however, their role in secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1), from the enteroendocrine L cell is unknown. Insulin induced a 1.4-fold increase in L cell GLP-1 release; however, secretion was potentiated to 2.1-fold in the presence of the F-actin depolymerizing agent, latrunculin B, suggesting that F-actin functions as a permissive barrier. In murine GLUTag L cells, insulin stimulated F-actin depolymerization and Cdc42 activation simultaneously, and these events occurred prior to detectable increases in insulin-induced GLP-1 release. After insulin treatment, Cdc42-dependent p21-activated kinase-1 (PAK1) activation was also detected, and transfection of small-interfering RNA against Cdc42 or of dominant-negative Cdc42(T17N) impaired insulin-stimulated PAK1 activation, actin remodeling, and GLP-1 secretion. Overexpression of kinase-dead PAK1(K299R) or PAK1 small interfering RNA similarly attenuated insulin-induced GLP-1 secretion. Knockdown or inhibition of Cdc42 and PAK1 activities also prevented activation of MAPK/ERK (MEK)-1/2-ERK1/2 by insulin, which was previously identified as a critical pathway for insulin-regulated GLP-1 release. Taken together, these data identify a novel signaling pathway in the endocrine L cell, whereby Cdc42 regulates actin remodeling, activation of the cannonical 1/2-ERK1/2 pathway and PAK1, and GLP-1 secretion in response to insulin.
Gene Therapy with Neurogenin 3 and Betacellulin Reverses Major Metabolic Problems in Insulin-Deficient Diabetic Mice
Authors: Yechoor Vijay , Liu Victoria , Paul Antoni , Lee Jeongkyung , Buras Eric , Ozer Kerem , Samson Susan , Chan Lawrence
Published: October 2009

Insulin deficiency in type 1 diabetes leads to disruptions in glucose, lipid, and ketone metabolism with resultant hyperglycemia, hyperlipidemia, and ketonemia. Exogenous insulin and hepatic insulin gene therapy cannot mimic the robust glucose-stimulated insulin secretion (GSIS) from native pancreatic islets. Gene therapy of streptozotocin-diabetic mice with neurogenin 3 (Ngn3) and betacellulin (Btc) leads to the induction of periportal oval cell-derived neo-islets that exhibit GSIS. We hence hypothesized that this gene therapy regimen may lead to a complete correction of the glucose and lipid metabolic abnormalities associated with insulin deficiency; we further hypothesized that the neo-islets formed in response to Ngn3-Btc gene delivery may display an ultrastructure and transcription profile similar to that of pancreatic islets. We injected streptozotocin-diabetic mice with helper-dependent adenoviral vectors carrying Ngn3 and Btc, which restored GSIS and reversed hyperglycemia in these animals. The treatment also normalized hepatic glucose secretion and reversed ketonemia. Furthermore, it restored hepatic glycogen content and reinstated hepatic lipogenesis-related gene transcripts back to nondiabetic levels. By transmission electron microscopy, the neo-islets displayed electron-dense granules that were similar in appearance to those in pancreatic islets. Finally, using RNA obtained by laser capture microdissection of the periportal neo-islets and normal pancreatic islets, we found that the neo-islets and pancreatic islets exhibited a very similar transcription profile on microarray-based transcriptome analysis. Taken together, this indicates that Ngn3-Btc gene therapy corrects the underlying dysregulated glucose and lipid metabolism in insulin-deficient diabetic mice by inducing neo-islets in the liver that are similar to pancreatic islets in structure and gene expression profile.
Free Fatty Acids Induce a Proinflammatory Response in Islets via the Abundantly Expressed Interleukin-1 Receptor I
Authors: Böni-Schnetzler Marianne , Boller Simone , Debray Sarah , Bouzakri Karim , Meier Daniel T. , Prazak Richard , Kerr-Conte Julie , Pattou Francois , Ehses Jan A. , Schuit Frans C. , Donath Marc Y.
Published: October 2009

Islets of patients with type 2 diabetes mellitus (T2DM) display features of an inflammatory process including elevated levels of the cytokine IL-1β, various chemokines, and macrophages. IL-1β is a master regulator of inflammation, and IL-1 receptor type I (IL-1RI) blockage improves glycemia and insulin secretion in humans with T2DM and in high-fat-fed mice pointing to a pivotal role of IL-1RI activity in intra-islet inflammation. Given the association of dyslipidemia and T2DM, we tested whether free fatty acids (FFA) promote the expression of proinflammatory factors in human and mouse islets and investigated a role for the IL-1RI in this response. A comparison of 22 mouse tissues revealed the highest IL-1RI expression levels in islets and MIN6 β-cells. FFA induced IL-1β, IL-6, and IL-8 in human islets and IL-1β and KC in mouse islets. Elevated glucose concentrations enhanced FFA-induced proinflammatory factors in human islets. Blocking the IL-1RI with the IL-1R antagonist (IL-1Ra) strongly inhibited FFA-mediated expression of proinflammatory factors in human and mouse islets. Antibody inhibition of IL-1β revealed that FFA stimulated IL-1RI activity via the induction of the receptor ligand. FFA-induced IL-1β and KC expression in mouse islets was completely dependent on the IL-1R/Toll-like receptor (TLR) docking protein Myd88 and partly dependent on TLR2 and -4. Activation of TLR2 in purified human β-cells and islets stimulated the expression of proinflammatory factors, and IL-1RI activity increased the TLR2 response in human islets. We conclude that FFA and TLR stimulation induce proinflammatory factors in islets and that IL-1RI engagement results in signal amplification.
Impact of Simvastatin on Adipose Tissue: Pleiotropic Effects in Vivo
Authors: Khan Tayeba , Hamilton Mark P. , Mundy Dorothy I. , Chua Streamson C. , Scherer Philipp E.
Published: October 2009

Statins belong to a class of drugs well known for their ability to reduce circulating low-density lipoprotein cholesterol. In addition to cholesterol lowering, they also exhibit potential antiinflammatory and antioxidant properties, suggesting that tissues other than liver may be targeted by statins to exert their beneficial metabolic effects. Adipocytes have received very little attention as a potential target of these drugs, possibly because adipocytes are not a major source of biosynthetic cholesterol. Here, we examine the effects of simvastatin on the secretory pathway, inflammation, and cellular metabolism of adipocytes as well as on whole-body insulin sensitivity. We find that statins have a selective effect on the secretion of the insulin-sensitizing adipokine adiponectin by reducing circulating levels of the high-molecular-weight form of adiponectin specifically with a concomitant increase in intracellular adiponectin levels. However, these effects on adiponectin do not translate into changes in metabolism or whole-body insulin sensitivity, potentially due to additional antiinflammatory properties of statins. In addition, ob/ob mice treated with statins have reduced adiposity and an altered ultrastructure of the plasma membrane with respect to caveolar histology. Our data demonstrate that statins have major effects on the cellular physiology of the adipocyte on multiple levels.
Smad1-Smad5 Ovarian Conditional Knockout Mice Develop a Disease Profile Similar to the Juvenile Form of Human Granulosa Cell Tumors
Authors: Middlebrook Brooke S. , Eldin Karen , Li Xiaohui , Shivasankaran Sujatha , Pangas Stephanie A.
Published: October 2009

Granulosa cell tumors (GCTs) of the ovary are rare sex cord stromal tumors. Although generally indolent, GCTs recur, and if not diagnosed and treated in early stages, survival rates are significantly shortened. Very little is known regarding GCT etiology. Because of the low incidence of cases and lack of standard diagnostics, mouse models for granulosa cell tumors are a valuable tool for studying GCTs and provide models for developing diagnostic and treatment strategies. We recently developed a novel mouse model of metastatic granulosa cell tumors by genetic deletion of the bone morphogenetic protein signaling transcription factors (SMADs) in granulosa cells of the ovary. Histological and serum hormone analyses reveal that this mouse model most closely resembles the juvenile form of GCT. We further analyzed samples of human juvenile GCT (JGCT) for expression of anti-Müllerian hormone and activation of two major signaling pathways: TGFβ/SMAD2/3 and wingless-related mouse mammary tumor virus integration site (Wnt)/β-catenin. The TGFβ family is active in mouse Smad1-Smad5 double knockout tumors, and here we show that this pathway, but not the β-catenin pathway, is activated in samples of human JGCT. These data suggest that the SMAD family, possibly through disruption of SMAD1/5 or activation of SMAD2/3 may contribute to the pathogenesis of JGCT in humans.
Glucocorticoids Amplify Dibutyl Phthalate-Induced Disruption of Testosterone Production and Male Reproductive Development
Authors: Drake Amanda J. , van den Driesche Sander , Scott Hayley M. , Hutchison Gary R. , Seckl Jonathan R. , Sharpe Richard M.
Published: October 2009

Common male reproductive abnormalities including cryptorchidism, hypospadias, and low sperm counts may comprise a testicular dysgenesis syndrome (TDS), resulting from fetal testis dysfunction during a critical developmental period involving reduced androgen production/action. The recent increase in TDS prevalence suggests environmental/lifestyle factors may be etiologically important. The developing fetus is exposed to multimodal challenges, and we hypothesized that exposure to a combination of factors rather than single agents may be important in the pathogenesis of TDS. We experimentally induced fetal testis dysfunction in rats via treatment of pregnant females daily from embryonic day (e) 13.5 to e21.5 with vehicle, 100 or 500 mg/kg · d dibutyl phthalate (DBP), 0.1 mg/kg · d dexamethasone (Dex), or a combination of DBP + Dex. In adulthood, penile length/normality, testis weight/descent, prostate weight, and plasma testosterone levels were measured plus anogenital distance (AGD) as a measure of androgen action within the masculinization programming window. Intratesticular testosterone and steroidogenic enzyme gene expression were measured in fetal testes at e17.5. High-dose DBP reduced fetal intratesticular testosterone and steroidogenic gene expression; induced mild hypospadias (31%) and cryptorchidism (53%); and reduced penile length, AGD, and testis and prostate weight in adulthood. Dex alone had no effect except to reduce birth weight but amplified the adverse effects of 500 mg/kg · d DBP and exacerbated the effects of 100 mg/kg · d DBP. All adverse effects were highly correlated to AGD, emphasizing the etiological importance of the masculinization programming window. These findings suggest that exposure to common environmental chemicals in combination with, for example, maternal stress, may increase the risk of common male reproductive abnormalities, with implications for human populations.
β-Cell-Specific Overexpression of Glutathione Peroxidase Preserves Intranuclear MafA and Reverses Diabetes in db/db Mice
Authors: Harmon Jamie S. , Bogdani Marika , Parazzoli Susan D. , Mak Sabrina S. M. , Oseid Elizabeth A. , Berghmans Marleen , LeBoeuf Renée C. , Robertson R. Paul
Published: October 2009

Chronic hyperglycemia causes oxidative stress, which contributes to damage in various tissues and cells, including pancreatic β-cells. The expression levels of antioxidant enzymes in the islet are low compared with other tissues, rendering the β-cell more susceptible to damage caused by hyperglycemia. The aim of this study was to investigate whether increasing levels of endogenous glutathione peroxidase-1 (GPx-1), specifically in β-cells, can protect them against the adverse effects of chronic hyperglycemia and assess mechanisms that may be involved. C57BLKS/J mice overexpressing the antioxidant enzyme GPx-1 only in pancreatic β-cells were generated. The biological effectiveness of the overexpressed GPx-1 transgene was documented when β-cells of transgenic mice were protected from streptozotocin. The transgene was then introgressed into the β-cells of db/db mice. Without use of hypoglycemic agents, hyperglycemia in db/db-GPx(+) mice was initially ameliorated compared with db/db-GPx(−) animals and then substantially reversed by 20 wk of age. β-Cell volume and insulin granulation and immunostaining were greater in db/db-GPx(+) animals compared with db/db-GPx(−) animals. Importantly, the loss of intranuclear musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) that was observed in nontransgenic db/db mice was prevented by GPx-1 overexpression, making this a likely mechanism for the improved glycemic control. These studies demonstrate that enhancement of intrinsic antioxidant defenses of the β-cell protects it against deterioration during hyperglycemia.
Convergence of 3′,5′-Cyclic Adenosine 5′-Monophosphate/Protein Kinase A and Glycogen Synthase Kinase-3β/β-Catenin Signaling in Corpus Luteum Progesterone Synthesis
Authors: Roy Lynn , McDonald Claudia A. , Jiang Chao , Maroni Dulce , Zeleznik Anthony J. , Wyatt Todd A. , Hou Xiaoying , Davis John S.
Published: October 2009

Progesterone secretion by the steroidogenic cells of the corpus luteum (CL) is essential for reproduction. Progesterone synthesis is under the control of LH, but the exact mechanism of this regulation is unknown. It is established that LH stimulates the LH receptor/choriogonadotropin receptor, a G-protein coupled receptor, to increase cAMP and activate cAMP-dependent protein kinase A (PKA). In the present study, we tested the hypothesis that cAMP/PKA-dependent regulation of the Wnt pathway components glycogen synthase kinase (GSK)-3β and β-catenin contributes to LH-dependent steroidogenesis in luteal cells. We observed that LH via a cAMP/PKA-dependent mechanism stimulated the phosphorylation of GSK3β at N-terminal Ser9 causing its inactivation and resulted in the accumulation of β-catenin. Overexpression of N-terminal truncated β-catenin (Δ90 β-catenin), which lacks the phosphorylation sites responsible for its destruction, significantly augmented LH-stimulated progesterone secretion. In contrast, overexpression of a constitutively active mutant of GSK3β (GSK-S9A) reduced β-catenin levels and inhibited LH-stimulated steroidogenesis. Chromatin immunoprecipitation assays demonstrated the association of β-catenin with the proximal promoter of the StAR gene, a gene that expresses the steroidogenic acute regulatory protein, which is a cholesterol transport protein that controls a rate-limiting step in steroidogenesis. Collectively these data suggest that cAMP/PKA regulation of GSK3β/β-catenin signaling may contribute to the acute increase in progesterone production in response to LH.
Phosphodiesterase 8B Gene Polymorphism Is Associated with Subclinical Hypothyroidism in Pregnancy
Authors: Shields Beverley M. , Freathy Rachel M. , Knight Bridget A. , Hill Anita , Weedon Michael N. , Frayling Timothy M. , Hattersley Andrew T. , Vaidya Bijay
Published: October 2009

Background: Maternal subclinical hypothyroidism is associated with a number of adverse outcomes in pregnancy. The Endocrine Society’s recent consensus guidelines have recommended treatment with T4 for this condition in pregnancy. The single nucleotide polymorphism rs4704397 in the phosphodiesterase 8B (PDE8B) gene has been found to be associated with altered serum TSH concentrations in the general population. We aimed to assess whether genetic variation in TSH due to the rs4704397 genotype affects the number of individuals classified as having subclinical hypothyroidism in pregnancy.

Methods: Serum TSH, FT4, FT3, and thyroid peroxidase antibodies (TPOAbs) were measured in 970 pregnant women at 28 wk gestation. rs4704397 genotype was available on 877 subjects. Reference range calculations were based on the TPOAb-negative women.

Results: TSH, but not FT4, FT3, or TPOAbs, varied with genotype and was highest in those with the AA genotype (median, 2.16, 1.84, and 1.73 mIU/liter for AA, AG, and GG genotypes, respectively; P = 0.0004). A greater proportion of women with the AA genotype had TSH concentrations above 4.21 mIU/liter, the upper limit of the reference range, compared with the AG and GG genotypes (9.6 vs. 3.5%, respectively; P = 0.004). Maternal PDE8B genotype was not associated with offspring birthweight or gestational age at delivery.

Conclusion: Genetic variation in TSH levels in pregnancy associated with the PDE8B rs4704397 genotype has implications for the number of women treated for subclinical hypothyroidism under current guidelines. Consideration should be made to individualization of normal ranges, potential effects on pregnancy outcome, and intention to treat for subclinical hypothyroidism in pregnancy.

Variation in the PDE8B gene leads to alteration in serum TSH concentration and different proportions of women picked up with subclinical hypothyroidism in pregnancy.
Modelling and stabilization of a series of self-balancing two-wheel vehicles
Authors: Karkoub M A , Zribi M , Parent M
Published: October 2009

This article deals with the modelling and control of a series of two-wheel vehicles connected via linear springs. The wheels of the two-wheel vehicles are connected to the side of the chassis via gear boxes and motors and rotate around the same axis. A non-linear dynamics model is derived for the system assuming that the vehicles move in tandem on a straight path. The system is underactuated and inherently unstable. A control scheme is designed to stabilize the vehicles all at the same time. The control technique used in this work is passivity based and guarantees the asymptotic convergence of the states towards stable trajectories. The non-linear control law is used to bring the states near the desired positions; subsequently, a second linear controller takes over to make the states converge towards the desired positions. The simulation results presented in this article show the success of the control schemes in controlling a system with two two-wheel vehicles.
Trans-Vacant and cis-Vacant 2:1 Layer Silicates: Structural Features, Identification, and Occurrence
Authors: Drits Victor A. , Zviagina Bella B.
Published: October 2009

A comprehensive study of clay minerals should include determination of the vacancy pattern of the dioctahedral sheet. The purpose of this report is to consider the advantages and limitations in various diffraction and non-diffraction methods for the determination of the layer types in clay minerals. Identification of trans-vacant (tv) and cis-vacant (cv) clay minerals reported here is based on powder X-ray diffraction (XRD) patterns calculated for different polytypes consisting of either tv or cv layers, on the simulation of experimental XRD patterns corresponding to illite or illite fundamental particles in which tv and cv layers are interstratified, and on the semi-quantitative assessment of the relative content of the layer types in the interstratified structures by generalized Méring’s rules. A simple and effective method for identification of tv and cv layers in dioctahedral 2:1 layer silicates employs thermal analysis and is based on different dehydroxylation temperatures for tv and cv illite and smectite layers.

Crystal chemical analysis of various dioctahedral 2:1 layer silicates consisting of tv and cv layers indicates that compositional control is present in the distribution of octahedral cations over trans- and cis-sites. In dioctahedral smectites the formation of tv and cv layers is related to the layer composition and local order-disorder in the distribution of isomorphous cations. Dioctahedral 1M micas with abundant Fe3+ and Mg occur only as tv varieties. In contrast, 1M-cv illite, as well as cv layers in illite fundamental particles of I-S, can form only as Fe- and Mg-poor varieties. In illites and illite fundamental particles of I-S consisting of tv and cv layers, cv layers prevail when the amounts of Al in octahedra and tetrahedra are >1.55 and >0.35 atoms per O10(OH)2, respectively.

The main factors responsible for the stability of cv and tv illites have been established. Monomineral cv 1M illite, its association with tv 1M illite, and interstratified cv/tv illite occur around ore deposits, in bentonites, and in sandstones mostly as a result of different types of hydrothermal activity. The initial material for their formation should be Al-rich, and hydrothermal fluids should be Mg- and Fe-poor.

Tv and cv smectites of volcanic origin differ in terms of octahedral cation composition and distribution of isomorphous octahedral cations. Mg-rich cv smectites have random distribution of isomorphous octahedral cations, whereas in Mg-bearing tv smectites octahedral Mg cations are dispersed so as to minimize the amount of Mg-OH-Mg arrangements.
Mineralogical Composition of Shallow Soils on Basic and Ultrabasic Rocks of East Fennoscandia and of the Ural Mountains, Russia
Authors: Lessovaia S. N. , Polekhovsky Yu. S.
Published: October 2009

The influence of epigenetic (pre-pedogenetic) alteration of basic and ultrabasic rocks leading to the formation of phyllosilicate mineral associations is not well known. The purpose of this study was to gain further understanding of the processes involved by investigating the mineral associations of shallow soils underlain by amphibolites and metamorphosed gabbro-diabases (East Fennoscandia) and by serpentinous dunites (olivinite) and metagabbro amphibolites (the Ural Mountains). Where phyllosilicates were absent from the bedrock, they were also absent from the sola. The pedogenic alteration of the initial mineral soil matrix was very weak and did not result in a significant accumulation of phyllosilicates in the soils (East Fennoscandia). Pedogenesis enhanced the transformation of phyllosilicates, a process initiated by epigenic rock alteration.

Phyllosilicates in the sola from basic and ultrabasic rocks of the Polar Urals were largely inherited according to their origin. The inherited phyllosilicate association of the sola from ultrabasic rocks included talc, serpentine, and chlorite. Saponite resulted from pedogenesis; its distribution in various thin soils depending on the processes of neoformation and decomposition, the latter probably taking place under the influence of lichens and moss.

Chlorite and illite and products of their transformation, including vermiculite, comprise the phyllosilicate association of a solum from basic rock, and traces of talc were found. The distribution of vermiculite and randomly interstratified chlorite-vermiculite (C-V) depended on the processes of chlorite vermiculitization and vermiculite decomposition.
Cation Exchange Reactions of Vermiculite With Cu-Triethylenetetramine as Affected by Mechanical and Chemical Pretreatment
Authors: Steudel Annett , Weidler Peter G. , Schuhmann Rainer , Emmerich Katja
Published: October 2009

The cation exchange capacity (CEC) is a characteristic property of expandable clay minerals, such as smectites and vermiculites. The aim of this work was to examine the cation exchange behavior of vermiculite using the Cu-triethylenetetramine (Cu-trien) CEC method and the influence of mechanical and chemical pretreatment, with the ammonium acetate method serving as a reference. The Cu-trien method makes rapid and direct CEC measurements possible. Three different kinds of mill were used to grind a vermiculite sample from Russia, in order to reduce the particle size to <10 µm. The Netzsch CGS 10 dry mill reduced the particle size more effectively than the other grinding methods. Chemical pretreatments were used to remove carbonates, organic matter, Fe oxides, and divalent exchangeable cations from vermiculite samples prior to CEC measurements. Subsamples of ground and chemically pretreated vermiculite samples were saturated with Na, Li, Mg, Ca, and Cu cations to determine the effect of exchangeable cations on measured CEC values. Chemical pretreatment, monovalent cation pretreatment, and 48 h of shaking time were needed to measure vermiculite CEC values effectively using the Cu-trien method.