bluuebunny/crossref_metadata_2025 huggingface dataset:
Migration of leukocytes across an endothelium-epithelium bilayer as a model of renal interstitial inflammation
Authors: Bijuklic Klaudija , Jennings Paul , Kountchev Jordan , Hasslacher Julia , Aydin Sonia , Sturn Daniel , Pfaller Walter , Patsch Josef R. , Joannidis Michael
Published: April 2007

Interstitial inflammation has emerged as a key event in the development of acute renal failure. To gain better insight into the nature of these inflammatory processes, the interplay between tubular epithelial cells, endothelial cells, and neutrophils (PMN) was investigated. A coculture transmigration model was developed, composed of human dermal microvascular endothelial (HDMEC) and human renal proximal tubular cells (HK-2) cultured on opposite sides of Transwell growth supports. Correct formation of an endoepithelial bilayer was verified by light and electron microscopy. The model was used to study the effects of endotoxin (LPS), tumor necrosis factor (TNF)-α, and α-melanocyte-stimulating hormone (α-MSH) by measuring PMN migration and cytokine release. To distinguish between individual roles of microvascular endothelial and epithelial cells in transmigration processes, migration of PMN was investigated separately in HK-2 and HDMEC monolayers. Sequential migration of PMN through endothelium and epithelium could be observed and was significantly increased after proinflammatory stimulation with either TNF-α or LPS (3.5 ± 0.58 and 2.76 ± 0.64-fold vs. control, respectively). Coincubation with α-MSH inhibited the transmigration of PMN through the bilayer after proinflammatory stimulation with LPS but not after TNF-α. The bilayers produced significant amounts of IL-8 and IL-6 mostly released from the epithelial cells. Furthermore, α-MSH decreased LPS-induced IL-6 secretion by 30% but had no significant effect on IL-8 secretion. We established a transmigration model showing sequential migration of PMN across microvascular endothelial and renal tubular epithelial cells stimulated by TNF-α and LPS. Anti-inflammatory effects of α-MSH in this bilayer model are demonstrated by inhibition on PMN transmigration and IL-6 secretion.
Simulated natural day lengths synchronize seasonal rhythms of asynchronously born male Siberian hamsters
Authors: Butler Matthew P. , Turner Kevin W. , Park Jin Ho , Butler James P. , Trumbull Justin J. , Dunn Sean P. , Villa Philip , Zucker Irving
Published: April 2007

Photoperiodism research has relied on static day lengths and abrupt transitions between long and short days to characterize the signals that drive seasonal rhythms. To identify ecologically relevant critical day lengths and to test the extent to which naturally changing day lengths synchronize important developmental events, we monitored nine cohorts of male Siberian hamsters ( Phodopus sungorus) born every 2 wk from 4 wk before to 12 wk after the summer solstice in a simulated natural photoperiod (SNP). SNP hamsters born from 4 wk before to 2 wk after the solstice underwent rapid somatic and gonadal growth; among those born 4–6 wk after the solstice, some delayed puberty by many weeks, whereas others manifested early puberty. Hamsters born eight or more weeks after the solstice failed to undergo early testicular development. The transition to delayed development occurred at long day lengths, which induce early puberty when presented as static photoperiods. The first animals to delay puberty may do so predominantly on the basis of postnatal decreases in day length, whereas in later cohorts, a comparison of postnatal day length to gestational day length may contribute to arrested development. Despite differences in timing of birth and timing of puberty, autumn gonadal regression and spring gonadal and somatic growth occurred at similar calendar dates in all cohorts. Incrementally changing photoperiods exert a strong organizing effect on seasonal rhythms by providing hamsters with a richer source of environmental timing cues than are available in simple static day lengths.
Profiling of the renal kinome: a novel tool to identify protein kinases involved in angiotensin II-dependent hypertensive renal damage
Authors: de Borst Martin H. , Diks Sander H. , Bolbrinker Juliane , Schellings Mark W. , van Dalen Mario B. A. , Peppelenbosch Maikel P. , Kreutz Reinhold , Pinto Yigal M. , Navis Gerjan , van Goor Harry
Published: April 2007

Regulation of protein kinase activities is crucial in both physiology and disease, but analysis is hampered by the multitude and complexity of kinase networks. We used novel peptide array chips containing 1,152 known kinase substrate sequences to profile different kinase activities in renal lysates from homozygous Ren2 rats, a model characterized by hypertension and angiotensin II (ANG II)-mediated renal fibrosis, compared with Sprague-Dawley (SD) control rats and Ren2 rats treated with an angiotensin-converting enzyme inhibitor (ACEi). Five-wk-old homozygous Ren2 rats were left untreated or treated with the ACEi ramipril (1 mg·kg−1·day−1) for 4 wk; age-matched SD rats served as controls ( n = 5 each). Peptide array chips were incubated with renal cortical lysates in the presence of radioactively labeled ATP. Radioactivity incorporated into the substrate motifs was measured to quantify kinase activity. A number of kinases with modulated activities, which might contribute to renal damage, were validated by Western blotting, immunoprecipitation, and immunohistochemistry. Relevant kinases identified by the peptide array and confirmed using conventional techniques included p38 MAP kinase and PDGF receptor-β, which were increased in Ren2 and reversed by ACEi. Furthermore, insulin receptor signaling was reduced in Ren2 compared with control rats, and G protein-coupled receptor kinase (GRK) activity decreased in Ren2 + ACEi compared with untreated Ren2 rats. Array-based profiling of tissue kinase activities in ANG II-mediated renal damage provides a powerful tool for identification of relevant kinase pathways in vivo and may lead to novel strategies for therapy.
Genome-wide analysis of PPARα activation in murine small intestine
Authors: Bünger Meike , van den Bosch Heleen M. , van der Meijde Jolanda , Kersten Sander , Hooiveld Guido J. E. J. , Müller Michael
Published: April 2007

The peroxisome proliferator-activated receptor alpha (PPARα) is a fatty acid-activated transcription factor that governs a variety of biological processes. Little is known about the role of PPARα in the small intestine. Since this organ is frequently exposed to high levels of PPARα ligands via the diet, we set out to characterize the function of PPARα in small intestine using functional genomics experiments and bioinformatics tools. PPARα was expressed at high levels in both human and murine small intestine. Detailed analyses showed that PPARα was expressed most highly in villus cells of proximal jejunum. Microarray analyses of total tissue samples revealed, that in addition to genes involved in fatty acid and triacylglycerol metabolism, transcription factors and enzymes connected to sterol and bile acid metabolism, including FXR and SREBP1, were specifically induced. In contrast, genes involved in cell cycle and differentiation, apoptosis, and host defense were repressed by PPARα activation. Additional analyses showed that intestinal PPARα-dependent gene regulation occurred in villus cells. Functional implications of array results were corroborated by morphometric data. The repression of genes involved in proliferation and apoptosis was accompanied by a 22% increase in villus height and a 34% increase in villus area of wild-type animals treated with WY14643. This is the first report providing a comprehensive overview of processes under control of PPARα in the small intestine. We show that PPARα is an important transcriptional regulator in small intestine, which may be of importance for the development of novel foods and therapies for obesity and inflammatory bowel diseases.
Metabolic and histochemical characteristics of fat and muscle tissues in homozygous or heterozygous pigs for the body composition QTL located on chromosome 7
Authors: Demars Julie , Riquet Juliette , Sanchez Marie-Pierre , Billon Yvon , Hocquette Jean-François , Lebret Bénédicte , Iannuccelli Nathalie , Bidanel Jean-Pierre , Milan Denis , Gondret Florence
Published: April 2007

Quantitative trait loci (QTL) influencing many traits including backfat thickness and carcass composition have been detected on porcine chromosome 7 (SSC7) in an F2 cross between Large White (LW) and Meishan (MS) pigs. However, the genes and controlled pathways underlying the QTL effects on body phenotype remain unknown. This study aimed at investigating the tissue characteristics at metabolic and cellular levels in pigs that were either homozygous or heterozygous for a body composition SSC7 QTL. A backcross pig (BC3) was first progeny tested to confirm its heterozygoty for the SSC7 QTL; results on all offspring ( n = 80) confirmed the QTL effects on body fatness. This boar was then mated with three sows known to be heterozygous for this QTL. In the subset of pigs per genotype, we found that heterozygous LWQTL7/MSQTL7pigs had smaller adipocytes in backfat, together with a lower basal rate of glucose incorporation into lipids and lower activities of selected lipogenic enzymes in backfat isolated cells, compared with homozygous LWQTL7/LWQTL7pigs. A higher number of adipocytes was also estimated in backfat of LWQTL7/MSQTL7animals compared with LWQTL7/LWQTL7pigs. The SSC7 QTL did not influence oxidative and glycolytic metabolisms of longissimus and trapezius muscles, as estimated by the activities of specific energy metabolism enzymes, or the myofiber type properties. Altogether, this study provides new evidence for an altered adipocyte cellularity in backfat of pigs carrying at least one MS allele for the SSC7 QTL. Some candidate genes known for their functions on adipocyte growth and differentiation are suggested.
Cardiac Myocyte Cell Cycle Control in Development, Disease, and Regeneration
Authors: Ahuja Preeti , Sdek Patima , MacLellan W. Robb
Published: April 2007

Cardiac myocytes rapidly proliferate during fetal life but exit the cell cycle soon after birth in mammals. Although the extent to which adult cardiac myocytes are capable of cell cycle reentry is controversial and species-specific differences may exist, it appears that for the vast majority of adult cardiac myocytes the predominant form of growth postnatally is an increase in cell size (hypertrophy) not number. Unfortunately, this limits the ability of the heart to restore function after any significant injury. Interest in novel regenerative therapies has led to the accumulation of much information on the mechanisms that regulate the rapid proliferation of cardiac myocytes in utero, their cell cycle exit in the perinatal period, and the permanent arrest (terminal differentiation) in adult myocytes. The recent identification of cardiac progenitor cells capable of giving rise to cardiac myocyte-like cells has challenged the dogma that the heart is a terminally differentiated organ and opened new prospects for cardiac regeneration. In this review, we summarize the current understanding of cardiomyocyte cell cycle control in normal development and disease. In addition, we also discuss the potential usefulness of cardiomyocyte self-renewal as well as feasibility of therapeutic manipulation of the cardiac myocyte cell cycle for cardiac regeneration.
Inositol Trisphosphate Receptor Ca2+Release Channels
Authors: Foskett J. Kevin , White Carl , Cheung King-Ho , Mak Don-On Daniel
Published: April 2007

The inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are a family of Ca2+release channels localized predominately in the endoplasmic reticulum of all cell types. They function to release Ca2+into the cytoplasm in response to InsP3produced by diverse stimuli, generating complex local and global Ca2+signals that regulate numerous cell physiological processes ranging from gene transcription to secretion to learning and memory. The InsP3R is a calcium-selective cation channel whose gating is regulated not only by InsP3, but by other ligands as well, in particular cytoplasmic Ca2+. Over the last decade, detailed quantitative studies of InsP3R channel function and its regulation by ligands and interacting proteins have provided new insights into a remarkable richness of channel regulation and of the structural aspects that underlie signal transduction and permeation. Here, we focus on these developments and review and synthesize the literature regarding the structure and single-channel properties of the InsP3R.
Arterial Stiffness Alterations during Hemodialysis: The Role of Dialysate Calcium
Authors: Kyriazis John , Katsipi Irene , Stylianou Kostas , Jenakis Nikolaos , Karida Anthoula , Daphnis Eugene
Published: April 2007

Background/Aims: We investigated the way dialysate calcium (dCa) level can influence arterial stiffness (AS), measured by stiffness index (SI), a surrogate of pulse wave velocity, and reflection index (RI), a measure of the amount of pulse wave reflection, derived by digital volume pulse (DVP). Methods: Fourteen hemodialysis (HD) patients underwent two consecutive midweek 4-hour HD treatments in randomized order with a low dCa concentration of 1.25 mmol/l (LdCa) and a high dCa concentration of 1.75 mmol/l (HdCa), respectively. Before HD and at 1-hour intervals during the subsequent 4-hour HD sessions, SI and RI measurements were obtained from DVP contour analysis. Blood pressure (BP) and heart rate (HR) were measured after each measurement of AS. Ionized serum calcium (iCa) was measured before HD and at 120 and 240 min into the HD session. Results: iCa increased and decreased by 15.3 and 5.4% in the HdCa and LdCa groups, respectively, at the end of HD. SI and RI increased by 5.7 and 6% in the HdCa group, respectively, whereas they remained unchanged in the LdCa group. The treatment effect and the time × treatment effect were significant for both indices (ANOVA). BP and HR changes did not differ between treatments. Conclusion: Contrary to LdCa, HdCa treatment induced a BP-independent, significant increase in measured AS parameters. In the long run, HD with LdCa, by reducing the incidence of HD-induced hypercalcemia, may have a beneficial role in minimizing the cardiovascular risk related to the intermittent, intradialytic increase in AS, inherent in the chronic use of HdCa.
The Generative Process, Music Composition and Games
Authors: Lefford Nyssim
Published: April 2007

The generative process through which artistic creators render artworks calls upon many perceptual and cognitive abilities. Because perceptions are knowledge and context dependent, creators and noncreators perceive structure in artworks differently. Analyses of artworks decoupled from the creating artists' perceptions offer an incomplete understanding of the generative process. The author's music composition games offer insight into the perceptions and styles of creators and provide a basis for empirical studies by enabling creators and non-creators to share a context and knowledge of constraints. Game results point toward more informed models of the generative process and new opportunities for the generative arts.
From the Avant-Garde: Re-Conceptualizing Cultural Origins in the Digital Media Art of Japan
Authors: Ippolito Jean M.
Published: April 2007

Misconceptions concerning digital artists in Japan make them out to be mere followers, savvy with technology but not necessarily the conceptual originators of their work. Examining the aesthetic and philosophical content of their work, however, reveals that their attitudes toward the exploration of process, performance and the inherent nature of materials come from innovative and daring avant-garde groups of the 1960s and 1970s in Japan, including the Gutai and Mono-ha groups, whose ideas predate those of the New York avant-garde schools, even outside of the technological milieu.
Crossing Conventions in Web-Based Art: Deconstruction as a Narrative Device
Authors: Robbins Christopher
Published: April 2007

The author explores the thesis that crossing the boundaries of genre within a medium requires the reassignment of defining constructs and can be used as a tool for deconstructing the medium. In this process, elements considered impartial or invisible become consciously manipulated tools, deconstructed and reassigned as narrative devices. The author posits that this reassessment is essential for the continued development of any medium or genre and discusses reasons for its recent renewed prominence. The author traces convention-crossing in several media, revealing attributes that are redefined by subversions, and explores subversions of digital media constructs, before discussing his own forays into web-based works that hinge on the artifice of convention.
Accountability in a Performance Appraisal Context: The Effect of Audience and Form of Accounting on Rater Response and Behavior
Authors: Mero Neal P. , Guidice Rebecca M. , Brownlee Amy L.
Published: April 2007

This study explored how context influences accountability in a performance appraisal context. Results demonstrate that audience characteristics influence rating quality, as raters accountable to higher status or mixed-status audiences provided more accurate ratings, whereas those accountable to a lower status audience provided more inflated ratings. Participant note taking also mediated the relationship between accountability to higher status or mixed-status audiences and rating accuracy. Raters required to account for ratings in person as opposed to in writing were more accurate when accountable to higher status or mixed audiences and provided more positive indicators of behavior when accountable to a lower status audience.
Timeframes and Absence Frameworks: A Test of Steers and Rhodes' (1978) Model of Attendance
Authors: Steel Robert P. , Rentsch Joan R. , Van Scotter James R.
Published: April 2007

Steers and Rhodes' (1978) model of employee attendance encompasses a variety of absence-predictor types (e.g., attitudes, personal factors, etc.). Recent conceptual frameworks suggest that the inconsistent findings on this model may be attributable, in part, to the use of absence timeframes that are incompatible with individual model components. Using data from 580 federal employees, a predictive analysis evaluated exogenous model predictors against absence criteria representing four different cumulation periods. Supplemental analysis explored the possibility of incremental endogenous-variable (i.e., Ability to Attend, Motivation to Attend) contributions. Results of both tests were consistent with a conclusion of partial model support.
Strategic Decision Making: The Effects of Cognitive Diversity, Conflict, and Trust on Decision Outcomes
Authors: Olson Bradley J. , Parayitam Satyanarayana , Yongjian Bao
Published: April 2007

Basing their hypotheses on information processing theory, the authors incorporate important group processes within strategic decision making. They examine the interrelationships of cognitive diversity, task conflict, and competence-based trust and their effects on decision outcomes. Their survey includes top management teams from 85 U.S. hospitals. They found that cognitive diversity has a strong positive relationship with task conflict and that competence-based trust strengthens this relationship. In addition, these results suggest that task conflict mediates the effects of cognitive diversity on decision outcomes.
Effort, Performance, and Conscientiousness: An Agency Theory Perspective
Authors: Fong Eric A. , Tosi Henry L.
Published: April 2007

The authors examine the moderating effects of conscientiousness on the relationships between agency controls and effort and agency controls and task performance. Results show that less conscientious individuals appear to increase effort through incentive alignment and monitoring, whereas conscientious individuals do not shirk with or without agency controls. Furthermore, results show that less conscientious individuals increase task performance through incentive alignment, but not through monitoring. The study confirms that motivation to act opportunistically differs between individuals unlike what is assumed by agency theory. Also, incentive alignment may be more effective than monitoring when attempting to align principal and agent interests.
Geographic information retrieval in a mobile environment: evaluating the needs of mobile individuals
Authors: Mountain David , MacFarlane Andrew
Published: April 2007

This paper describes research that aims to define the information needs of mobile individuals, to implement a mobile information system that can satisfy those needs, and finally to evaluate the performance of that system with end-users. First a review of the emerging discipline of geographic information retrieval (GIR) is presented as background to the more specific issue of mobile information retrieval. Following this, a user needs study is described evaluating the requirements of potential users of a mobile information system; the study finds that there is a strong geographic component to users' information needs. Next, four geographic post-query filters are described which attempt to represent the region of space associated with an individual's query made at some specific spatial location. These filters are spatial proximity (distance in space), temporal proximity (travel time), speed-heading prediction surfaces (likelihood of visiting locations) and visibility (locations that can be seen). Two of these filters — spatial proximity and speed-heading prediction surfaces — are implemented in a mobile information system and subsequently evaluated with users in an outdoor setting. The results of evaluation suggest that retrieved information to which post-query geographic filters have been applied is considered more relevant than unfiltered information, and that users find information sorted by spatial proximity to be more relevant than that sorted by a prediction surface of likely future locations. The paper closes with a discussion of the wider implications of these results for developers of mobile information systems and location-based services.
Popularity and findability through log analysis of search terms and queries: the case of a multilingual public service website
Authors: Ravid Gilad , Bar-Ilan Judit , Baruchson-Arbib Shifra , Rafaeli Sheizaf
Published: April 2007

SHIL on the Web is the website of the Israeli Citizens' Advice Bureau. It provides information about rights, social benefits, government and public services and civil obligations. Activity on the site approaches 10,000 pages visited per day. It has interfaces in four languages: Hebrew, Arabic, Russian and English. Logfile analysis of the SHIL website revealed to our surprise that about 60.7% of the requests reaching SHIL from external sites (excluding requests from robots) are from general search engines (e.g. Google and MSN), and users reach a specific page on the site linked from the search results page. This finding seems to indicate that the site is not known well enough to the public. On the other hand the site is very active, thus it seems to serve Israeli citizens well, even without being a well known brand. In this paper we analyzed the external requests coming from search engines. The analysis is based on the 266,295 queries from search engines that reached SHIL during March—October 2005. Studying queries submitted to search engines is a novel technique for analyzing the access patterns to the site and provides a better understanding of the user needs and intentions than analyzing the distribution of the visited pages only. We are not aware of any previous study that analyzed the relation between the query submitted to the search engine and the webpage the user clicked on the search results page. Since search engines provide snippets, when the user clicks on a specific page he already has some information on what is to be found on the page and the user makes a conscious decision to click on the specific result. Thus, this type of analysis provides additional information about the users' actual information needs.
An index rewriting scheme using compression for flash memory database systems
Authors: Byun Siwoo , Huh Moonhaeng , Hwang Hoyoung
Published: April 2007

Flash memories are one of the best media to support portable computers' storage areas in mobile database environments. Their features include non-volatility, low power consumption, and fast access time for read operations, which are sufficient to present flash memories as major database storage components for portable computers. However, we need to improve traditional index management schemes based on B-Tree due to the relatively slow characteristics of flash operations, as compared to RAM memory. In order to achieve this goal, we propose a new index rewriting scheme based on a compressed index called F-Tree. F-Tree-based index management improves index operation performance by compressing pointers and keys in tree nodes and rewriting the nodes without a slow erase operation in node insert/delete processes. Based on the results of the performance evaluation, we conclude that the F-Tree-based scheme outperforms the traditional schemes.
My Sassy Girl
Authors: Xiying Wang  , Petula, Sik Ying Ho
Published: April 2007

The Korean film My Sassy Girl was very popular among young people in urban China in 2001. After the release of the movie, the new image of the “sassy girl” emerged in different media. This study uses the media image of the sassy girl as a stimulus material in interviews and focus groups to explore how young men and women make sense of women's aggression in dating relationships. This qualitative study is mainly based on two focus groups and in-depth interviews with 20 informants (13 female and 7 male). The study sheds light on how the competing and multilayered discourses in contemporary China regarding gender, love, and sex have left some space for young adults to justify women's aggression in dating relationships. We see how young adults in Beijing situate themselves within this set of social cultural discourses and make use of them to “do” their gender through their aggressive behavior and interactions with each other. New images of men and women are thereby created.
Correlates of Partner Violence for Incarcerated Women and Men
Authors: Robertson Kirsten , Murachver Tamar
Published: April 2007

This study examines partner violence within an incarcerated sample of women and men. Specifically, it focused on the relationship between explicit and implicit attitudes to the perpetration and victimization of violence. Findings revealed that violence was bidirectional, with males and females equally likely to report being the perpetrator or victim of violence. The attitudes and beliefs associated with violence were similar regardless of gender, type of violence (physical or psychological), or whether individuals were the victim or perpetrator of violence. Hostility to women was the most significant factor associated with perpetrating and condoning partner violence. Hostility to women in combination with implicit beliefs condoning violence were the strongest predictors for suffering physical violence. Victims' self-reported communication problems uniquely predicted their suffering of psychological violence. The explanation for and consequences of these results are discussed.
Perceptions of Smoking and Nonsmoking Peers: The Value of Smoker and Nonsmoker Prototypes in Predicting Smoking Onset and Regular Smoking Among Adolescents
Authors: Spijkerman Renske , Van Den Eijnden Regina J. J. M. , Engels Rutger C. M. E.
Published: April 2007

Adolescents' perceptions of persons their age who smoke cigarettes (also known as prototypes of smoking peers) play a critical role in an adolescent's decision to start smoking. However, adolescents' perceptions of their peers who do not smoke (prototypes of nonsmoking peers) could be implicated in adolescents' smoking decisions as well. In the present study, the authors examined the additional role of nonsmoker prototypes in adolescents' smoking onset and regular smoking. At seven high schools, Dutch students ( n = 1,035) between the ages of 12 and 15 years who were attending the eighth grade provided self-reported data on their smoker and nonsmoker prototypes and smoking behavior during a baseline and 6-month follow-up measurement. Logistic regression analyses showed that both smoker and nonsmoker prototypes assessed at Time 1 predicted smoking onset by Time 2 among nonsmoking adolescents. However, only nonsmoker prototypes predicted regular smoking among adolescents who smoked occasionally at baseline.
Factors Associated With Mental Health and Juvenile Justice Involvement Among Children With Severe Emotional Disturbance
Authors: Graves Kelly N. , Frabutt James M. , Shelton Terri L.
Published: April 2007

Recent research has highlighted the fact that there is an overrepresentation of children with mental health problems in the juvenile justice system. Thus, this study uses a clinical sample of children receiving mental health services to examine demographic (e.g., age, ethnicity), person-level (e.g., anxious and/or depressed), family-level (e.g., number of transitions in living situations), and school-level factors associated with being involved in the mental health and juvenile justice service systems (i.e., dual involvement). Analyses were conducted separately by gender to investigate differences in dual involvement and possible differences in the predictors of dual involvement. For boys and girls, older adolescents and a higher number of living transitions were associated with dual involvement. For girls only, depression and/or anxiety and social problems were associated with dual involvement. The findings highlight the need for greater collaboration among service systems given the strong overlap between mental health and juvenile justice involvement for many children.
Controlling Suburban and Small-Town Hoods
Authors: Liederbach John
Published: April 2007

We currently lack systematic observational data concerning street-level interactions between police and juveniles in nonurban jurisdictions. This study uses systematic social observation (SSO) methods to examine the nature and character of police encounters with juveniles age 13 to 17 years in 20 suburban and small-town jurisdictions in terms of (a) the types of problems nonurban officers confronted while interacting with juveniles, (b) the actions taken by officers to resolve these problems, and (c) the discretionary decision making of officers in arrest situations involving juveniles. The findings suggest similarities and differences between nonurban officers and previously studied urban officers in terms of how they interact with juveniles. A discussion regarding how these findings may be interpreted is offered, highlighting the general need for more research concerning street-level interactions between police and juveniles, and the importance of including samples of nonurban communities in studies of police–juvenile encounters.
Correlation between Soluble Endoglin, Vascular Endothelial Growth Factor Receptor-1, and Adipocytokines in Preeclampsia
Authors: Masuyama Hisashi , Nakatsukasa Hideki , Takamoto Norio , Hiramatsu Yuji
Published: April 2007

Context: Recent reports have demonstrated that soluble endoglin (sEng), an antiangiogenic protein thought to impair TGF-β binding to receptors, and soluble vascular endothelial growth factor receptor (sVEGFR)-1 play important roles in the pathophysiology of preeclampsia (PE). Moreover, insulin resistance, which is greatly influenced by adipocytokines, characterizes PE.

Objectives: We examined possible links between sEng, VEGF, sVEGFR, and adipocytokines in the pathophysiology of PE.

Study Design: We performed a cross-sectional study in 30 PE patients and controls matched for gestational age and body mass index. Blood samples were collected soon after disease onset. We measured serum concentrations of leptin, adiponectin, sEng, VEGF, placental growth factor (PlGF), and sVEGFR [soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble fetal liver kinase 1 (sFlk-1)], and examined the placental protein content of sEng and sFlt-1.

Results: sEng concentrations in PE patients (60.9 ± 28.8 ng/ml) were significantly higher than those in controls (11.2 ± 4.4 ng/ml). There was a significant correlation between sEng and sFlt-1 or PlGF. Moreover, there were significant differences in mean blood pressure between the high and low sEng groups, and in proteinuria between the high and low sFlt-1 groups, and significant differences in placental sEng and sFlt-1 contents between patients with and without severe hypertension or proteinuria. sEng was also correlated positively with adiponectin levels and negatively with the leptin to adiponectin ratio.

Conclusions: Along with sFlt-1 and PlGF, sEng might play a role in the pathophysiology of PE, especially in elevating blood pressure, while the association with hypoadiponectinemia and the high leptin to adiponectin ratio in pregnancy seem to be risk factors for PE.
The Effects of Metabolic Syndrome Versus Infectious Burden on Inflammation, Severity of Coronary Atherosclerosis, and Major Adverse Cardiovascular Events
Authors: Dai Dao-Fu , Lin Jou-Wei , Kao Jia-Horng , Hsu Chih-Neng , Chiang Fu-Tien , Lin Jiunn-Lee , Chou Yi-Hua , Hsu Kwan-Lih , Tseng Chuen-Den , Tseng Yung-Zu , Hwang Juey-Jen
Published: April 2007

Background: The clinical predictors of inflammation in atherosclerosis remain controversial. The objective of this study was to compare the associations of metabolic factors vs. infectious burden (IB) with inflammation, the severity of coronary atherosclerosis, and major adverse cardiovascular events (MACEs).

Design, Setting, and Patients: Coronary angiography with Gensini score was applied to assess the severity of coronary atherosclerosis in 568 patients with coronary artery disease. Metabolic syndrome (MS) score (0–5) was defined according to the modified criteria of National Cholesterol Education Program Adult Treatment Panel III. IB score (0–7) was defined as the number of seropositivities to several agents.

Results: IB score was not associated with plasma C-reactive protein (CRP) concentration, Gensini score, or the risk of MACE. In contrast, MS score significantly correlated with both plasma CRP concentration and Gensini score (P < 0.001 for both). MS score and plasma CRP concentration were also significantly associated with the risk of MACE (hazard ratios 1.51, P < 0.001; and 1.90, P = 0.002, respectively).

Conclusion: Compared with IB, metabolic abnormalities have a more prominent association with the degree of inflammation, the severity of coronary atherosclerosis, and the risk of MACE in patients with coronary artery disease.
Genes for Enzymes Regulating Dehydroepiandrosterone Sulfonation Are Associated with Levels of Dehydroepiandrosterone Sulfate in Polycystic Ovary Syndrome
Authors: Goodarzi Mark O. , Antoine Heath J. , Azziz Ricardo
Published: April 2007

Context: The adrenal androgen (AA) metabolite dehydroepiandrosterone sulfate (DHEAS) is often elevated in women with polycystic ovary syndrome (PCOS); AA excess in PCOS appears to be, in part, a heritable trait. Dehydroepiandrosterone (DHEA) sulfonation is controlled by the enzymes DHEA sulfotransferase (SULT2A1) and steroid sulfatase (STS). Polymorphisms in these genes have not been evaluated as modulators of DHEAS level in PCOS.

Objective: The aim was to test the hypothesis that variants in the SULT2A1 and STS genes are associated with DHEAS levels in women with PCOS.

Design: Women with and without PCOS were genotyped for seven single nucleotide polymorphisms (SNPs) in SULT2A1 and seven SNPs in STS. SNPs and haplotypes were determined and tested for association with DHEAS.

Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles.

Participants: A total of 287 white women with PCOS and 187 controls participated in the study.

Main Measurements: SULT2A1 and STS genotype and DHEAS levels were measured.

Results: In women with PCOS, SNP rs182420 in SULT2A1 was associated with DHEAS (P = 0.0035). Two haplotypes carrying the minor allele of rs182420 were also associated with DHEAS (P = 0.04 each). Variants within STS were not associated with DHEAS level. No associations were observed in control women.

Conclusion: This study presents genetic evidence suggesting a potential role of SULT2A1, but not STS, in the inherited AA excess of PCOS.
Endocrine Abnormalities in Patients with Fanconi Anemia
Authors: Giri Neelam , Batista Dalia L. , Alter Blanche P. , Stratakis Constantine A.
Published: April 2007

Background: Fanconi anemia (FA) is an inherited disorder with chromosomal instability, bone marrow failure, developmental defects, and a predisposition to cancer. Systematic and comprehensive endocrine function data in FA are limited.

Objective: We studied a cohort of FA patients enrolled in the National Cancer Institute’s Inherited Bone Marrow Failure Syndrome study.

Study Design and Patients: Retrospective review of the medical records of 45 FA patients (ages 2–49 yr), 23 of whom were intensively evaluated at the National Institutes of Health. Anthropometric measurements, GH, IGF-I, IGF binding protein-3, thyroid, gonadal hormone, lipid levels, glucose homeostasis, brain imaging, and bone mineral density were obtained in these latter patients.

Results: Endocrine abnormalities were present in 73%, including short stature and/or GH deficiency (51%), hypothyroidism (37%), midline brain abnormalities (17%) (these patients had very short stature and 60% were GH-deficient); abnormal glucose/insulin metabolism (39%); obesity (27%); dyslipidemia (55%); and metabolic syndrome (21%). Patients with any endocrine abnormality were shorter than those without; only GH deficiency correlated significantly with short stature (P = 0.01). In addition, 65% of peripubertal or postpubertal patients had gonadal dysfunction. Ninety-two percent of the patients 18 yr or older had osteopenia or osteoporosis.

Conclusions: Endocrine dysfunction is widespread in children and adults with FA; we expand the FA phenotype to include early onset osteopenia/osteoporosis and lipid abnormalities. Despite the reputation of FA as a progressive, lethal disease, proper management of the full spectrum of FA-related endocrinopathy offers major opportunities to reduce morbidity and improve quality of life. Our findings emphasize the need for comprehensive endocrine and metabolic evaluation and long-term follow-up in patients with FA.
The Presence of the d3-Growth Hormone Receptor Polymorphism Is Negatively Associated with Fetal Growth but Positively Associated with Postnatal Growth in Healthy Subjects
Authors: Jensen Rikke Beck , Vielwerth Signe , Larsen Torben , Greisen Gorm , Leffers Henrik , Juul Anders
Published: April 2007

Context: A common polymorphism in the GH receptor (GHR) gene has been linked to increased growth response in GH-treated patients. No former study has focused on the association to prenatal growth.

Objective: The aim of the study was to evaluate the association between the d3-GHR isoforms and spontaneous pre- and postnatal growth.

Design: A prospective study was conducted on third-trimester fetal growth velocity (FGV), birth weight, birth length, and postnatal growth.

Setting: The study was conducted at Copenhagen University Hospital.

Participants: A total of 115 healthy adolescents were divided into those born small for gestational age (SGA) and appropriate for gestational age with or without intrauterine growth restriction.

Main Outcome Measures: FGV was measured by serial ultrasonography, birth weight, birth length, and adolescent height. Isoforms of the d3-GHR gene (fl/fl, d3/fl, and d3/d3) were determined.

Results: The prevalence of the d3-GHR isoforms was 50% but differed among the groups (P = 0.006), with a high prevalence (88%) in the group born SGA with verified intrauterine growth restriction. The d3-GRH allele were associated with decreased third-trimester FGV (P = 0.05) in SGA subjects. In the entire cohort, carriers of the d3-GHR allele had a significantly increased height (−0.10 vs. 0.34 sd score; P = 0.017) and change in height from birth to adolescence compared with carriers of the full-length GHR allele (0.57 vs. −0.02 sd score; P = 0.005).

Conclusions: This study showed an increased spontaneous postnatal growth velocity in the carriers of the d3-GHR allele. Interestingly, we found the opposite effect on prenatal growth in the SGA group, with a decreased FGV in carriers of the d3-GHR allele.
Surface-Scanning Mutational Analysis of Protein Arginine Methyltransferase 1: Roles of Specific Amino Acids in Methyltransferase Substrate Specificity, Oligomerization, and Coactivator Function
Authors: Lee David Y. , Ianculescu Irina , Purcell Daniel , Zhang Xing , Cheng Xiaodong , Stallcup Michael R.
Published: April 2007

Protein arginine methyltransferase 1 (PRMT1) is an arginine-specific protein methyltransferase that methylates a number of proteins involved in transcription and other aspects of RNA metabolism. Its role as a transcriptional coactivator for nuclear receptors involves its ability to bind to other coactivators, such as glucocorticoid receptor-interacting protein 1 (GRIP1), as well as its ability to methylate histone H4 and coactivators such as peroxisome proliferator-activated receptor γ coactivator-1α. Its ability to form homodimers or higher-order homo-oligomers also is important for its methyltransferase activity. To understand the function of PRMT1 further, 19 surface residues were mutated, based on the crystal structure of PRMT1. Mutants were characterized for their ability to bind and methylate various substrates, form homodimers, bind GRIP1, and function as a coactivator for the androgen receptor in cooperation with GRIP1. We identified specific surface residues that are important for methylation substrate specificity and binding of substrates, for dimerization/oligomerization, and for coactivator function. This analysis also revealed functional relationships between the various activities of PRMT1. Mutants that did not dimerize well had poor methyltransferase activity and coactivator function. However, surprisingly, all dimerization mutants exhibited increased GRIP1 binding, suggesting that the essential PRMT1 coactivator function of binding to GRIP1 may require dissociation of PRMT1 dimers or oligomers. Three different mutants with altered substrate specificity had widely varying coactivator activity levels, suggesting that methylation of specific substrates is important for coactivator function. Finally, identification of several mutants that exhibited reduced coactivator function but appeared normal in all other activities tested, and finding one mutant with very little methyltransferase activity but normal coactivator function, suggested that these mutated surface residues may be involved in currently unknown protein-protein interactions that are important for coactivator function.
A crucial role for Olig2 in white matter astrocyte development
Authors: Cai Jeff , Chen Ying , Cai Wen-Hui , Hurlock Edward C. , Wu Heng , Kernie Steven G. , Parada Luis F. , Lu Q. Richard
Published: April 2007

The mechanisms underlying astrocyte heterogeneity in the developing mouse brain are poorly understood. The bHLH transcription factor Olig2 is essential for motoneuron and oligodendrocyte formation; however, its role in astrocyte development remains obscure. During cortical development, Olig2 is transiently expressed in immature developing astrocytes at neonatal stages and is progressively downregulated in astrocytes at late postnatal stages. To assess the function of Olig2 in astrocyte formation, we conditionally ablated Olig2 in a spatiotemporally controlled manner. In the Olig2-ablated cortex and spinal cord, the formation of astrocytes in the white matter is severely compromised. Temporally controlled mutagenesis revealed that postnatal Olig2 function is required for astrocyte differentiation in the cerebral white matter. By contrast, astrocytes in the cortical gray matter are formed, but with sustained GFAP upregulation in the superficial layers. Cell type-specific mutagenesis and fate-mapping analyses indicate that abnormal astrocyte formation is at least in part attributable to the loss of Olig2 in developing astrocytes and their precursors. Thus, our studies uncover a crucial role for Olig2 in white matter astrocyte development and reveal divergent transcriptional requirements for,and developmental sources of, morphologically and spatially distinct astrocyte subpopulations.
Prolonged Renal Failure Secondary to Antithymocyte Globulin Treatment in Severe Aplastic Anemia
Authors: Barakat Ruchdi K , Schmolck Johann P , Finkel Kevin W , Foringer John R
Published: April 2007

Objective:

To report a case of acute renal failure in a patient with severe aplastic anemia after administration of antithymocyte globulin (ATG).

Case Summary:

A 41-year-old man diagnosed with severe aplastic anemia was treated with ATG and cyclosporine. After one dose of ATG (3012 mg. 40 mg/kg), the patient developed anuric acute renal failure, with serum creatinine 3.4 mg/dL (1.2 mg/dL at baseline) and blood urea nitrogen (BUN) 29 mg/dL (13 mg/dL at baseline), which required intermittent hemodialysis. Renal failure resolved with cessation of the drug, serum creatinine and BUN returned to baseline levels, and the patient no longer required hemodialysis.

Discussion:

ATG is a purified and concentrated gamma globulin, primarily a monomeric immunoglobulin G from hyperimmune serum of horses. It is widely used to treat severe aplastic anemia and to manage acute transplant rejection. This patient had no other confounding factors for the cause of the renal failure. An objective causality assessment using the Naranjo probability scale suggested that ATG was the probable cause of the acute renal failure. Primary glomerular disease was not excluded, as a renal biopsy was not performed.

Conclusions:

The association between renal injury and administration of ATG remains unclear; therefore, we recommend that renal function be assessed and carefully monitored prior to and after administration of ATG.
An Intersubunit Trigger of Channel Gating in the Muscle Nicotinic Receptor
Authors: Mukhtasimova Nuriya , Sine Steven M.
Published: April 2007

Binding of neurotransmitter triggers gating of synaptic receptor channels, but our understanding of the structures that link the binding site to the channel is just beginning to develop. Here, we identify an intersubunit triggering element required for rapid and efficient gating of muscle nicotinic receptors using a structural model of theTorpedoreceptor at 4 Å resolution, recordings of currents through single receptor channels, measurements of inter-residue energetic coupling, and functional consequences of disulfide trapping. Mutation of the conserved residues, αTyr 127, εAsn 39, and δAsn 41, located at the two subunit interfaces that form the agonist binding sites, markedly attenuates acetylcholine-elicited channel gating; mutant cycle analyses based on changes in the channel gating equilibrium constant reveal strong energetic coupling among these residues. After each residue is substituted with Cys, oxidizing conditions that promote disulfide bond formation attenuate gating of mutant, but not wild-type receptors. Gating is similarly attenuated when the Cys substitutions are confined to either of the binding-site interfaces, but can be restored by reducing conditions that promote disulfide bond breakage. Thus, the Tyr–Asn pair is an intersubunit trigger of rapid and efficient gating of muscle nicotinic receptors.