bluuebunny/crossref_metadata_2025 huggingface dataset:
Japanese encephalitis virus induces matrix metalloproteinase-9 expression via a ROS/c-Src/PDGFR/PI3K/Akt/MAPKs-dependent AP-1 pathway in rat brain astrocytes
Authors: Yang Chuen-Mao , Lin Chih-Chung , Lee I-Ta , Lin Yi-Hsin , Yang Caleb M , Chen Wei-June , Jou Mei-Jie , Hsiao Li-Der
Published: January 2012

Background

Japanese encephalitis virus (JEV) infection is a major cause of acute encephalopathy in children, which destroys central nervous system (CNS) cells, including astrocytes and neurons. Matrix metalloproteinase (MMP)-9 has been shown to degrade components of the basal lamina, leading to disruption of the blood-brain barrier (BBB) and to contribute to neuroinflammatory responses in many neurological diseases. However, the detailed mechanisms of JEV-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells) are largely unclear.

Methods

In this study, the effect of JEV on expression of MMP-9 was determined by gelatin zymography, western blot analysis, RT-PCR, and promoter assay. The involvement of AP-1 (c-Jun and c-Fos), c-Src, PDGFR, PI3K/Akt, and MAPKs in these responses were investigated by using the selective pharmacological inhibitors and transfection with siRNAs.

Results

Here, we demonstrate that JEV induces expression of pro-form MMP-9 via ROS/c-Src/PDGFR/PI3K/Akt/MAPKs-dependent, AP-1 activation in RBA-1 cells. JEV-induced MMP-9 expression and promoter activity were inhibited by pretreatment with inhibitors of AP-1 (tanshinone), c-Src (PP1), PDGFR (AG1296), and PI3K (LY294002), and by transfection with siRNAs of c-Jun, c-Fos, PDGFR, and Akt. Moreover, JEV-stimulated AP-1 activation was inhibited by pretreatment with the inhibitors of c-Src, PDGFR, PI3K, and MAPKs.

Conclusion

From these results, we conclude that JEV activates the ROS/c-Src/PDGFR/PI3K/Akt/MAPKs pathway, which in turn triggers AP-1 activation and ultimately induces MMP-9 expression in RBA-1 cells. These findings concerning JEV-induced MMP-9 expression in RBA-1 cells imply that JEV might play an important role in CNS inflammation and diseases.
Study of the expression levels of Hepatocyte nuclear factor 4 alpha and 3 beta in patients with different outcome of HBV infection
Authors: Chen En-Qiang , Sun Hui , Feng Ping , Gong Dao-Yin , Liu Cong , Bai Lang , Yang Wen-Bing , Lei Xue-Zhong , Chen Li-Yu , Huang Fei-Jun , Tang Hong
Published: January 2012

Hepatocyte nuclear factors 4 alpha (HNF4α) and 3 beta (HNF3β) are members of a group of liver-enriched transcription factors (LETFs) that play important roles in regulating the replication of hepatitis B virus (HBV) and liver inflammation. However, the relationship of the level of HNF4α and HNF3β with the severity of HBV-infected liver diseases is unclear. In this study, liver tissue samples from different types of HBV patients were collected, and HNF4α and HNF3β expression were detected by immunohistochemistry. The expression of HNF4α was significant higher in patients with severe hepatitis B(SHB) than those with chronic hepatitis B(CHB) and liver cirrhosis(LC) (both P < 0.05), but similar between patients with CHB and LC (P > 0.05). And the expression of HNF3β was similar among patients with CHB, LC and SHB (P > 0.05 for all pairwise comparison). This suggests that the expression level of HNF4α was different in patients with different outcome of HBV infection, high expression level of HNF4α may correlate with occurrence of SHB
Programmed cell death in type II neuroblast lineages is required for central complex development in the Drosophila brain
Authors: Jiang Yanrui , Reichert Heinrich
Published: January 2012

Background

The number of neurons generated by neural stem cells is dependent upon the regulation of cell proliferation and by programmed cell death. Recently, novel neural stem cells that amplify neural proliferation through intermediate neural progenitors, called type II neuroblasts, have been discovered, which are active during brain development in Drosophila. We investigated programmed cell death in the dorsomedial (DM) amplifying type II lineages that contribute neurons to the development of the central complex in Drosophila, using clonal mosaic analysis with a repressible cell marker (MARCM) and lineage-tracing techniques.

Results

A significant number of the adult-specific neurons generated in these DM lineages were eliminated by programmed cell death. Programmed cell death occurred during both larval and pupal stages. During larval development, approximately one-quarter of the neuronal (but not glial) cells in the lineages were eliminated by apoptosis before the formation of synaptic connectivity during pupal stages. Lineage-tracing experiments documented the extensive contribution of intermediate neural progenitor-containing DM lineages to all of the major modular substructures of the adult central complex. Moreover, blockage of apoptotic cell death specifically in these lineages led to prominent innervation defects of DM-derived neural progeny in the major neuropile substructures of the adult central complex.

Conclusions

Our findings indicate that significant neural overproliferation occurs normally in type II DM lineage development, and that elimination of excess neurons in these lineages through programmed cell death is required for the formation of correct neuropile innervation in the developing central complex. Thus, amplification of neuronal proliferation through intermediate progenitors and reduction of neuronal number through programmed cell death operate in concert in type II neural stem-cell lineages during brain development.
Cardiac autonomic impairment and chronotropic incompetence in fibromyalgia
Authors: da Cunha Ribeiro Roberta Potenza , Roschel Hamilton , Artioli Guilherme Gianini , Dassouki Thalita , Perandini Luiz Augusto , Calich Ana Luisa , de Sá Pinto Ana Lúcia , Lima Fernanda Rodrigues , Bonfá Eloísa , Gualano Bruno
Published: January 2012

Introduction

We aimed to gather knowledge on the cardiac autonomic modulation in patients with fibromyalgia (FM) in response to exercise and to investigate whether this population suffers from chronotropic incompetence (CI).

Methods

Fourteen women with FM (age: 46 ± 3 years; body mass index (BMI): 26.6 ± 1.4 kg/m2) and 14 gender-, BMI- (25.4 ± 1.3 kg/m2), and age-matched (age: 41 ± 4 years) healthy individuals (CTRL) took part in this cross-sectional study. A treadmill cardiorespiratory test was performed and heart-rate (HR) response during exercise was evaluated by the chronotropic reserve. HR recovery (deltaHRR) was defined as the difference between HR at peak exercise and at both first (deltaHRR1) and second (deltaHRR2) minutes after the exercise test.

Results

FM patients presented lower maximal oxygen consumption (VO2 max) when compared with healthy subjects (22 ± 1 versus CTRL: 32 ± 2 mL/kg/minute, respectively; P < 0.001). Additionally, FM patients presented lower chronotropic reserve (72.5 ± 5 versus CTRL: 106.1 ± 6, P < 0.001), deltaHRR1 (24.5 ± 3 versus CTRL: 32.6 ± 2, P = 0.059) and deltaHRR2 (34.3 ± 4 versus CTRL: 50.8 ± 3, P = 0.002) than their healthy peers. The prevalence of CI was 57.1% among patients with FM.

Conclusions

Patients with FM who undertook a graded exercise test may present CI and delayed HR recovery, both being indicative of cardiac autonomic impairment and higher risk of cardiovascular events and mortality.
Hyperuricemia and untreated gout are poor prognostic markers among those with a recent acute myocardial infarction
Authors: Krishnan Eswar , Pandya Bhavik J , Lingala Bharathi , Hariri Ali , Dabbous Omar
Published: January 2012

Introduction

Patients with a history of myocardial infarction (MI) are often at risk for complications, including subsequent MI and death. Use of prognostic markers may aid in preventing these poor outcomes. Hyperuricemia is associated with increased risk for coronary heart disease (CHD) and/or mortality; however, it is unknown if serum urate (sUA) levels predict outcomes in patients with previous MI. The purpose of this study was to assess hyperuricemia as a biomarker of CHD outcomes in such patients.

Methods

These were post hoc analyses of datasets from the Aspirin Myocardial Infarction Study, a 1:1 randomized, double-blind clinical trial, conducted from 1975 to 1979, that examined mortality rates following daily aspirin administration over three years in individuals with documented MI. The primary outcome measures were all-cause death, CHD mortality, coronary incidence, and stroke by quartile of baseline sUA. A sub-analysis of all outcome measures in the presence or absence of gouty arthritis was also performed.

Results

Of 4,524 enrolled participants, data on 4,352 were analyzed here. All outcomes were greatest for patients in the fourth sUA quartile. In multivariate regression models, the hazard ratios (HR) for patients in the highest quartile were 1.88 for all-cause mortality (95% confidence interval (CI), 1.45 to 2.46), 1.99 for CHD mortality (95% CI, 1.49 to 2.66), and 1.36 for coronary incidence (95% CI, 1.08 to 1.70). Participants with untreated gout had an adjusted hazard ratio ranging from 1.5 to 2.0 (all P < 0.01) for these outcomes. Participants with gout who were receiving treatment did not exhibit this additional risk.

Conclusions

sUA and untreated gout may be independent prognostic markers for poor all-cause and CHD mortality in patients with recent acute MI.
Maraviroc, a chemokine receptor-5 antagonist, fails to demonstrate efficacy in the treatment of patients with rheumatoid arthritis in a randomized, double-blind placebo-controlled trial
Authors: Fleishaker Dona L , Garcia Meijide Juan A , Petrov Andriy , Kohen Michael David , Wang Xin , Menon Sujatha , Stock Thomas C , Mebus Charles A , Goodrich James M , Mayer Howard B , Zeiher Bernhardt G
Published: January 2012

Introduction

The purpose of this study was to determine whether maraviroc, a human CC chemokine receptor 5 (CCR5) antagonist, is safe and effective in the treatment of active rheumatoid arthritis (RA) in patients on background methotrexate (MTX).

Methods

This phase IIa study comprised two distinct components: an open-label safety study of the pharmacokinetics (PK) of MTX in the presence of maraviroc, and a randomized, double-blind, placebo-controlled, proof-of-concept (POC) component. In the PK component, patients were randomized 1:1 to receive maraviroc 150 or 300 mg twice daily (BID) for four weeks. In the POC component, patients were randomized 2:1 to receive maraviroc 300 mg BID or placebo for 12 weeks. Patients were not eligible for inclusion in both components.

Results

Sixteen patients were treated in the safety/PK component. Maraviroc was well tolerated and there was no evidence of drug-drug interaction with MTX. One hundred ten patients were treated in the POC component. The study was terminated after the planned interim futility analysis due to lack of efficacy, at which time 59 patients (38 maraviroc; 21 placebo) had completed their week 12 visit. There was no significant difference in the number of ACR20 responders between the maraviroc (23.7%) and placebo (23.8%) groups (treatment difference -0.13%; 90% CI -20.45, 17.70; P = 0.504). The most common all-causality treatment-emergent adverse events in the maraviroc group were constipation (7.8%), nausea (5.2%), and fatigue (3.9%).

Conclusions

Maraviroc was generally well tolerated over 12 weeks; however, selective antagonism of CCR5 with maraviroc 300 mg BID failed to improve signs and symptoms in patients with active RA on background MTX.

Trial Registration

ClinicalTrials.gov: NCT00427934
A longitudinal study of the association between dietary factors, serum lipids, and bone marrow lesions of the knee
Authors: Doré Dawn , de Hoog Jonathon , Giles Graham , Ding Changhai , Cicuttini Flavia , Jones Graeme
Published: January 2012

Introduction

Bone marrow lesions (BMLs) play an important role in knee osteoarthritis, but their etiology is not well understood. The aim of this longitudinal study was to describe the association between dietary factors, serum lipids, and BMLs.

Methods

In total, 394 older men and women (mean age, 63 years; range, 52 to 79) were measured at baseline and approximately 2.7 years later. BMLs were determined by using T2-weighted fat-saturation magnetic resonance imaging (MRI) by measuring the maximal area of the lesion. Nutrient intake (total energy, fat, carbohydrate, protein, and sugar) and serum lipids were assessed at baseline.

Results

Cross-sectionally, dietary factors and lipids were not significantly associated with BMLs. Energy, carbohydrate, and sugar intake (but not fat) were positively associated with a change in BML size (β = 15.44 to 19.27 mm2 per 1 SD increase; all P < 0.05). High-density lipoprotein (HDL) cholesterol tended to be negatively associated with BML change (β = -11.66 mm2 per 1 SD increase; P = 0.088).

Conclusions

Energy, carbohydrate, and sugar intake may be risk factors for BML development and progression. HDL cholesterol seems protective against BMLs. These results suggest that macronutrients and lipids may be important in BML etiology and that dietary modification may alter BML natural history.
Evaluation of a Breast Cancer Nomogram for Predicting Risk of Ipsilateral Breast Tumor Recurrences in Patients With Ductal Carcinoma in Situ After Local Excision
Authors: Yi Min , Meric-Bernstam Funda , Kuerer Henry M. , Mittendorf Elizabeth A. , Bedrosian Isabelle , Lucci Anthony , Hwang Rosa F. , Crow Jaime R. , Luo Sheng , Hunt Kelly K.
Published: January 2012

Purpose

Prediction of patients at highest risk for ipsilateral breast tumor recurrence (IBTR) after local excision of ductal carcinoma in situ (DCIS) remains a clinical concern. The aim of our study was to evaluate a published nomogram from Memorial Sloan-Kettering Cancer Center to predict for risk of IBTR in patients with DCIS from our institution.

Patients and Methods

We retrospectively identified 794 patients with a diagnosis of DCIS who had undergone local excision from 1990 through 2007 at the MD Anderson Cancer Center (MDACC). Clinicopathologic factors and the performance of the Memorial Sloan-Kettering Cancer Center nomogram for prediction of IBTR were assessed for 734 patients who had complete data.

Results

There was a marked difference with respect to tumor grade, prevalence of necrosis, initial presentation, final margins, and receipt of endocrine therapy between the two cohorts. The biggest difference was that more patients received radiation in the MDACC cohort (75% at MDACC v 49% at MSKCC; P < .001). Follow-up time in the MDACC cohort was longer than in the MSKCC cohort (median 7.1 years v 5.6 years), and the recurrence rate was lower in the MDACC cohort (7.9% v 11%). The median 5-year probability of recurrence was 5%, and the median 10-year probability of recurrence was 7%. The nomogram for prediction of 5- and 10-year IBTR probabilities demonstrated imperfect calibration and discrimination, with a concordance index of 0.63.

Conclusion

Predictive models for IBTR in patients with DCIS who were treated with local excision are imperfect. Our current ability to accurately predict recurrence on the basis of clinical parameters alone is limited.
Meta-Analysis of Psychosocial Interventions to Reduce Pain in Patients With Cancer
Authors: Sheinfeld Gorin Sherri , Krebs Paul , Badr Hoda , Janke Elizabeth Amy , Jim Heather S.L. , Spring Bonnie , Mohr David C. , Berendsen Mark A. , Jacobsen Paul B.
Published: January 2012

Purpose

Pain is one of the most common, burdensome, and feared symptoms experienced by patients with cancer. American Pain Society standards for pain management in cancer recommend both pharmacologic and psychosocial approaches. To obtain a current, stable, and comprehensive estimate of the effect of psychosocial interventions on pain—an important clinical topic—we conducted a meta-analysis of randomized controlled studies among adult patients with cancer published between 1966 and 2010.

Methods

Three pairs of raters independently reviewed 1,681 abstracts, with a systematic process for reconciling disagreement, yielding 42 papers, of which 37 had sufficient data for meta-analysis. Studies were assessed for quality using a modified seven-item Physiotherapy Evidence Database (PEDro) coding scheme. Pain severity and interference were primary outcome measures.

Results

Study participants (N = 4,199) were primarily women (66%) and white (72%). The weighted averaged effect size across studies for pain severity (38 comparisons) was 0.34 (95% CI, 0.23 to 0.46; P < .001), and the effect size for pain interference (four comparisons) was 0.40 (95% CI, 0.21 to 0.60; P < .001). Studies that monitored whether treatment was delivered as intended had larger effects than those that did not (P = .04).

Conclusion

Psychosocial interventions had medium-size effects on both pain severity and interference. These robust findings support the systematic implementation of quality-controlled psychosocial interventions as part of a multimodal approach to the management of pain in patients with cancer.
Treatment Patterns Among Medicaid-Eligible Women With Breast Cancer in Georgia: Are Patterns Different Under the Breast and Cervical Cancer Prevention and Treatment Act?
Authors: Adams E. Kathleen , Chien Li-Nien , Gabram-Mendola Sheryl G.A.
Published: January 2012

The Breast and Cervical Cancer Prevention and Treatment Act program in Georgia creates a quicker pathway for low-income, uninsured women with breast cancer to access services and receive more treatment than women enrolled in traditional Medicaid eligibility groups.
US Cancer Center Implementation of ASCO/Oncology Nursing Society Chemotherapy Administration Safety Standards
Authors: Weingart Saul N. , Li Justin W. , Zhu Junya , Morway Laurinda , Stuver Sherri O. , Shulman Lawrence N. , Hassett Michael J.
Published: January 2012

Given wide variation in the implementation of ASCO/Oncology Nursing Society chemotherapy administration safety standards at US cancer centers, there are significant opportunities for improvement.
Improved Insulin Sensitivity after Long-Term Treatment with AT1 Blockers Is Not Associated with PPARγ Target Gene Regulation
Authors: Müller-Fielitz Helge , Landolt Julia , Heidbreder Marc , Werth Stefan , Vogt Florian M. , Jöhren Olaf , Raasch Walter
Published: January 2012

In both cell culture experiments and in vivo studies, a number of angiotensin II type 1 (AT1) receptor antagonists activated the peroxisome proliferator-activated receptor-γ (PPARγ). This mechanism has been discussed to be, at least in part, responsible for the improvement in glucose metabolism observed in animal studies and clinical trials. To investigate whether the PPARγ-dependent mechanism may represent a valid target for chronic therapy, spontaneously hypertensive rats (SHR) were fed either with a cafeteria diet (CD) or standard chow. CD-fed SHR were simultaneously treated with either telmisartan (TEL; 8 mg/kgbody weight·d) or candesartan (CAND; 10 mg/kgbody weight·d) for 3 months because TEL, but not CAND, has been demonstrated to be a strong activator of PPARγ. After 3 months, chow- and CD-fed controls were hypertensive, whereas TEL and CAND treatment resulted in normalized blood pressures in SHR. Body weight and the amount of abdominal fat (determined by magnetic resonance imaging) were higher in CD- than in chow-fed SHR. After TEL or CAND, body weight, abdominal fat quantity, and adipocyte size returned to normal. In glucose tolerance tests, the glucose responses were comparable in the TEL- and CAND-treated SHR and obese controls, whereas the insulin response was almost halved by AT1 blockade. Expression of PPARγ target genes aP2, FAT CD36, FASn, and PEPCK remained unaltered at the protein level in visceral fat after TEL and CAND compared with the CD-fed controls. Because the expression of examined PPARγ target genes was not affected, we concluded that improved insulin sensitivity after long-term treatment with AT1 blockers was not related to a PPARγ-dependent mechanism.
Molecular Characterization and Biological Function of Neuroendocrine Regulatory Peptide-3 in the Rat
Authors: Fujihara Hiroaki , Sasaki Kazuki , Mishiro-Sato Emi , Ohbuchi Toyoaki , Dayanithi Govindan , Yamasaki Motoo , Ueta Yoichi , Minamino Naoto
Published: January 2012

Neuroendocrine regulatory peptide (NERP)-3, derived from the neurosecretory protein VGF (non-aconymic), is a new biologically active peptide identified through peptidomic analysis of the peptides secreted by an endocrine cell line. Using a specific antibody recognizing the C-terminal region of NERP-3, immunoreactive (ir)-NERP-3 was identified in acid extracts of rat brain and gut as a 30-residue NERP-3 with N-terminal pyroglutamylation. Assessed by radioimmunoassay, ir-NERP-3 was more abundant in the brain, including the posterior pituitary (PP), than in the gut. Immunohistochemistry demonstrated that ir-NERP-3 was significantly increased in the suprachiasmatic nucleus, the magnocellular division of the paraventricular nucleus, and the external layer of the median eminence, but not in the supraoptic nucleus, after dehydration. The immunoreactivity was, however, markedly decreased in all of these locations after chronic salt loading. Intracerebroventricular administration of NERP-3 in conscious rats induced Fos expression in a subset of arginine vasopressin (AVP)-containing neurons in the supraoptic nucleus and the magnocellular division of the paraventricular nucleus. On in vitro isolated rat PP preparations, NERP-3 caused a significant AVP release in a dose-related manner, suggesting that NERP-3 in the PP could be an autocrine activator of AVP release. Taken together, the present results suggest that NERP-3 in the hypothalamo-neurohypophyseal system may be involved in the regulation of body fluid balance.
Early Postnatal Hyperalimentation Impairs Renal Function via SOCS-3 Mediated Renal Postreceptor Leptin Resistance
Authors: Alcazar Miguel Angel Alejandre , Boehler Eva , Rother Eva , Amann Kerstin , Vohlen Christina , von Hörsten Stephan , Plank Christian , Dötsch Jörg
Published: January 2012

Early postnatal hyperalimentation has long-term implications for obesity and developing renal disease. Suppressor of cytokine signaling (SOCS) 3 inhibits phosphorylation of signal transducer and activator of transcription (STAT) 3 and ERK1/2 and thereby plays a pivotal role in mediating leptin resistance. In addition, SOCS-3 is induced by both leptin and inflammatory cytokines. However, little is known about the intrinsic-renal leptin synthesis and function. Therefore, this study aimed to elucidate the implications of early postnatal hyperalimentation on renal function and on the intrinsic-renal leptin signaling. Early postnatal hyperalimentation in Wistar rats during lactation was induced by litter size reduction at birth (LSR) either to LSR10 or LSR6, compared with home cage control male rats. Assessment of renal function at postnatal day 70 revealed decreased glomerular filtration rate and proteinuria after LSR6. In line with this impairment of renal function, renal inflammation and expression as well as deposition of extracellular matrix molecules, such as collagen I, were increased. Furthermore, renal expression of leptin and IL-6 was up-regulated subsequent to LSR6. Interestingly, the phosphorylation of Stat3 and ERK1/2 in the kidney, however, was decreased after LSR6, indicating postreceptor leptin resistance. In accordance, neuropeptide Y (NPY) gene expression was down-regulated; moreover, SOCS-3 protein expression, a mediator of postreceptor leptin resistance, was strongly elevated and colocalized with NPY. Thus, our findings not only demonstrate impaired renal function and profibrotic processes but also provide compelling evidence of a SOCS-3-mediated intrinsic renal leptin resistance and concomitant up-regulated NPY expression as an underlying mechanism.
Phylogenetic Comparisons Implicate Sex Hormone-Binding Globulin in “Masculinization” of the Female Spotted Hyena (Crocuta crocuta)
Authors: Hammond Geoffrey L. , Miguel-Queralt Solange , Yalcinkaya Tamer M. , Underhill Caroline , Place Ned J. , Glickman Stephen E. , Drea Christine M. , Wagner Aaron P. , Siiteri Pentti K.
Published: January 2012

Exposures to sex steroids during fetal development are thought to contribute to the unique urogenital anatomy and social dominance of the female spotted hyena: overt phenotypes not shared by other hyenids (i.e. striped hyena, brown hyena, and aardwolf). Because both androgens and estrogens influence development of genitalia and behavior, and because plasma SHBG regulates their access to tissues, we compared the Shbg gene sequences, structures, and steroid-binding properties in the four extant hyenids. We found the hyenid Shbg genes (>95% identical) and mature protein sequences (98% identical) are highly conserved. As in other mammals, the hyenid SHBG all bind 5α-dihydrotestosterone with high affinity (Kd = 0.62–1.47 nm), but they also bind estrone and dehydroepiandrosterone with similarly high affinity, and this unusual property was attributed to specific amino acids within their SHBG steroid-binding sites. Phylogenetic comparisons also indicated that the spotted hyena SHBG precursor uniquely lacks two leucine residues and has a L15W substitution within its secretion signal polypeptide, the reduced size and hydrophobicity of which markedly decreases the production of SHBG and may therefore explain why serum SHBG concentrations in male and female spotted hyenas are approximately five times lower than in other hyenids. This is important because low plasma SHBG concentrations in spotted hyenas will increase exposure to biologically active androgens and estrogen as well as to their precursors (dehydroepiandrosterone and estrone), which may contribute to the masculinized external genitalia of female spotted hyenas and to female social dominance over males.
Uncovering Novel Reproductive Defects in Neurokinin B Receptor Null Mice: Closing the Gap Between Mice and Men
Authors: Yang Jasmine J. , Caligioni Claudia S. , Chan Yee-Ming , Seminara Stephanie B.
Published: January 2012

Patients bearing mutations in TAC3 and TACR3 (which encode neurokinin B and its receptor, respectively) have sexual infantilism and infertility due to GnRH deficiency. In contrast, Tacr3−/− mice have previously been reported to be fertile. Because of this apparent phenotypic discordance between mice and men bearing disabling mutations in Tacr3/TACR3, Tacr3 null mice were phenotyped with close attention to pubertal development, estrous cyclicity, and fertility. Tacr3−/− mice demonstrated normal timing of preputial separation and day of first estrus, markers of sexual maturation. However, at postnatal d 60, Tacr3−/− males had significantly smaller testes and lower FSH levels than their wild-type littermates. Tacr3−/− females had lower uterine weights and abnormal estrous cyclicity. Approximately half of Tacr3−/− females had no detectable corpora lutea on ovarian histology at postnatal d 60. Despite this apparent ovulatory defect, all Tacr3−/− females achieved fertility when mated. However, Tacr3−/− females were subfertile, having both reduced numbers of litters and pups per litter. The subfertility of these animals was not due to a primary ovarian defect, because they demonstrated a robust response to exogenous gonadotropins. Thus, although capable of fertility, Tacr3-deficient mice have central reproductive defects. The remarkable ability of acyclic female Tacr3 null mice to achieve fertility is reminiscent of the reversal of hypogonadotropic hypogonadism seen in a high proportion of human patients bearing mutations in TACR3. Tacr3 mice are a useful model to examine the mechanisms by which neurokinin B signaling modulates GnRH release.
The Effectiveness of Using a Web-Based Applet to Teach Concepts of Linear Programming: An Experiment in Active Learning
Authors: Kydd Christine T.
Published: January 2012

The graphical solution method to a two-variable linear program (LP) provides valuable insights about the general nature of multivariable linear programming models. As a result, introductory operations research/management science textbooks typically present a graphical solution method to a two-variable LP as a prelude to the presentation of more complex problems. Construction of a two-dimensional feasible region combined with iso-profit (or iso-cost) lines on a blackboard or overhead projector can be tedious, at best. Even with tools such as PowerPoint, that include drawing tools, it is difficult to show students what happens in a graphical LP as constraint lines and iso-profit lines shift around on a graph. To overcome this hurdle, this paper presents a Web-based Java script applet that was used by both instructors and students to graphically illustrate/learn fundamental concepts of LP models. It then describes the results of a study that compares student performance on exams of those who did use the applet versus those who did not. Results show that the students who used the applet to learn about LP concepts performed significantly better than those who did not. Implications for using such active learning techniques and models in the classroom are discussed.
The reach of early intervention: a case study of a Sure Start programme
Authors: Hannon Peter , Pickstone Caroline , Suckling Rupert , Crofts Deborah
Published: January 2012

Early intervention is part of policy concerning educational, health and social inequalities but whether programmes reach those for whom they are intended is under-researched. This article reports on a case study of one programme within the national Sure Start initiative in England, 1999-2005. Reach was conceptualised as having two aspects: contact and use. It was found that, conceptualised as contact, programme reach was virtually 100%. Conceptualised as use, it varied according to services within the programme and to some extent according to family characteristics. The relatively more disadvantaged families were reached almost as much as other families. Implications for practice and policy are discussed.
Troponin T Percentiles from a Random Population Sample, Emergency Room Patients and Patients with Myocardial Infarction
Authors: Hammarsten Ola , Fu Michael L X , Sigurjonsdottir Runa , Petzold Max , Said Lina , Landin-Wilhelmsen Kerstin , Widgren Bengt , Larsson Mårten , Johanson Per
Published: January 2012

BACKGROUND

High-sensitivity cardiac troponin T (cTnT) assays detect small clinically important myocardial infarctions (MI) but also yield higher rates of false-positive results owing to increased concentrations sometimes present in patients without MI. Better understanding is needed of factors influencing the 99th percentile of cTnT concentrations across populations and the frequency of changes in cTnT concentrations >20% often used in combination with increased cTnT concentrations for diagnosis of MI.

METHODS

cTnT percentiles were determined by use of the Elecsys® hscTnT immunoassay (Modular® Analytics E170) in a random population sample, in emergency room (ER) patients, and in patients with non–ST-elevation MI (NSTEMI). Changes in cTnT concentrations were determined in hospitalized patients without MI.

RESULTS

The 99th cTnT percentile in a random population sample (median age, 65 years) was 24 ng/L. In ER patients <65 years old without obvious conditions that increase cTnT, the 99th cTnT percentile was 12 ng/L with little age dependence, whereas in those >65 years old it was 82 ng/L and highly age dependent. In hospitalized patients without MI the 97.5th percentile for change in the cTnT concentration was 51%–67%. cTnT remained below the 99th percentile (12 ng/L) in 1% of patients with NSTEMI until 8.5 h after symptom onset and 6 h after ER arrival.

CONCLUSIONS

Age >65 years was the dominant factor associated with increased cTnT in ER patients. This age association was more prominent in ER patients than in a random population sample. Changes in serial cTnT concentrations >20% were common in hospitalized patients without MI.
Use of Circulating MicroRNAs to Diagnose Acute Myocardial Infarction
Authors: Devaux Yvan , Vausort Mélanie , Goretti Emeline , Nazarov Petr V , Azuaje Francisco , Gilson Georges , Corsten Maarten F , Schroen Blanche , Lair Marie-Lise , Heymans Stephane , Wagner Daniel R
Published: January 2012

BACKGROUND

Rapid and correct diagnosis of acute myocardial infarction (MI) has an important impact on patient treatment and prognosis. We compared the diagnostic performance of high-sensitivity cardiac troponin T (hs-cTnT) and cardiac enriched microRNAs (miRNAs) in patients with MI.

METHODS

Circulating concentrations of cardiac-enriched miR-208b and miR-499 were measured by quantitative PCR in a case-control study of 510 MI patients referred for primary mechanical reperfusion and 87 healthy controls.

RESULTS

miRNA-208b and miR-499 were highly increased in MI patients (>105-fold, P < 0.001) and nearly undetectable in healthy controls. Patients with ST-elevation MI (n= 397) had higher miRNA concentrations than patients with non–ST-elevation MI (n = 113) (P < 0.001). Both miRNAs correlated with peak concentrations of creatine kinase and cTnT (P < 10−9). miRNAs and hs-cTnT were already detectable in the plasma 1 h after onset of chest pain. In patients who presented <3 h after onset of pain, miR-499 was positive in 93% of patients and hs-cTnT in 88% of patients (P= 0.78). Overall, miR-499 and hs-cTnT provided comparable diagnostic value with areas under the ROC curves of 0.97. The reclassification index of miR-499 to a clinical model including several risk factors and hs-cTnT was not significant (P = 0.15).

CONCLUSION

Circulating miRNAs are powerful markers of acute MI. Their usefulness in the establishment of a rapid and accurate diagnosis of acute MI remains to be determined in unselected populations of patients with acute chest pain.
Conspectus interruptus: Dirty Harry and the trouble in the Fillmore district
Authors: ROLLS ALISTAIR
Published: January 2012

When people think of Dirty Harry, they tend to imagine a figure of absolute determination and unbreakable resolution. The opening film of the Dirty Harry Franchise (Dirty Harry, 1971) does not, however, fit neatly with that understanding. Indeed, Harry is deeply torn; his is a story
of hesitation. And as such, he vacillates across any number of dichotomies. Neither wholly objective nor wholly subjective, for example, he is always both inside and outside the action. In this article, we analyse the film's, and Harry's, fundamental hesitation through the lens of Freudian
psychoanalysis, and in particular the essay on the splitting of the ego. In so doing, we suggest that Scorpio is a representation of Harry's ego that has to be resolved. Indeed, the whole film can be read as the working through of trauma stemming from a primal scene, which we locate in the
trouble that Harry famously, but enigmatically, had in the Fillmore district. These events, which the mayor specifically does not want to see repeated, are shown to be repeated continually, and in various formats, throughout the film, to the extent that, in the final (psycho)analysis, the
trouble in the Fillmore district is all there is. The film can thus be said to be about the working through of traumatic events and the repairing of a fractured ego. In conclusion, we explore how the events of the Fillmore district are about the balancing of seeing and being seen, with all
that this entails for a heightening of our own responsibilities as voyeurs in Harry's San Francisco.
At one remove from reality: Style bloggers and outfit posts
Authors: FINDLAY ROSIE
Published: January 2012

In recent years, the outfit post - a defining feature of personal style blogs - has changed the seeing and being seen of dressing. What was once primarily a corporeal and temporal social practice has developed into a performed virtual reality in which style bloggers literally fashion
their identity on their blogs. Style blogs thus become both the space in which bloggers realize their own fashioned self and the site at which their readers experience them as stylish. These blogs have become a place for the display of the new and a realization of the imaginary, as well as
a site to record 'what I wore'. This article explores the phenomenon of outfit posts, focusing on the interanimation therein between bloggers' styled selves and their clothing. Central to this discussion will be a consideration of the ways that outfit posts are both performative and expressive
presentations of self.
Amongst women: Male romance authors and Irish chick lit author, Andrew O’Connor
Authors: RYAN MARY
Published: January 2012

It has been claimed that writing is not directly 'gendered'; that all, or at least most, subjects are universal and can be written about by anyone. Regardless of this, novels written by men, those seen to emphasize 'men's' values, have traditionally been granted more recognition and
respect. So-called 'women's fiction' - arguably some of the most commercially successful fiction in recent decades - is often criticized and ridiculed, though the reason for this may be as simple as the fact that, particularly in the case of male critics and reviewers, they simply may not
comprehend women's fiction, with its natural and understandable emphasis on woman-centred values and experiences, and, as such, feel uncomfortable in a strange, woman-centred environment. This raises an interesting point: whether typically woman-centred fiction would gain more respect and
recognition if it were written by men. This article will examine the situation of male writers of woman-centred fiction; it will discuss the reception these authors have typically received; and it will explore the work of Andrew O'Connor - also known as A. O'Connor - something of a rarity
as a male chick lit author, with the aim of revealing whether a man can effectively and convincingly write about women and their experiences.
Hidden injuries of class and bourgeoisie dreams: Casino workers, traditional shipbuilders and boutique hotels in Macao
Authors: ONG CHIN-EE
Published: January 2012

With more than US$15 billion invested in Macao's gaming industry between 2005 and 2010 for the creation of world-class casinos, theatres, theme parks and luxury shopping malls, intense casino development transformed Macao's urban landscape. Much is said about Macao's astonishing
rate of tourist arrivals and staggering gross domestic product in the last four years as a combined result of longstanding casino tourism and nascent World Heritage tourism in the 29.5-sq km postcolonial territory. Less is known about its 500,000 residents and workers. Building upon existing
work that interrogates the salient connection between the self and class position of workers, I examine the 'hidden injuries of class' or the difficulties for the individual worker in terms of achieving dignity and respect in capitalistic Macao. Specifically, drawing upon life and work history
interviews with former traditional shipbuilders and casino workers, I examine both pre-casino and casino Macao's class experiences and relations. In doing so, I seek to relate the present with the past and illustrate how the building of Macao's bourgeoisie dreams in forms of the territory's
pursuit of casino resorts and boutique hotels brought about 'hidden injuries of class' for two different generations of Macao proletariats.
Between automoción patria and maternal combustion: Driving through change in Sor Citroën (1967)
Authors: PROUT RYAN
Published: January 2012

Critics, fans and bloggers have recently articulated a polarized set of responses to the 1967 film Sor Citroën alongside a growth in nostalgia for early models of smallformat Spanish cars. This article uses key texts by Virginia Scharff and Deborah Clark on the history of women's
automobilism to posit that the dissonances and paradoxes that have previously been identified in Sor Citroën reflect not only the contradictions of a stagnant desarrollista politics but also the ambiguities and paradoxes of a car culture that has its roots in a patriarchal paradigm of
automobile production and consumption. The article further posits that Sor Citroën reflects an inflection point in Spanish automotive culture and that its central character anticipates debate over the relationship between cars, reproduction and female autonomy. Dialogue with post-transitional
Spanish film asks if Sor Citroën was a decisive departure from automoción patria or simply a brief detour from its trajectory.
Travel movies and the creation of a global memory: The cases of Lisbon and Granada
Authors: MASCARENHAS-MATEUS JOÃO , SALVADOR-VENTURA FRANCISCO
Published: January 2012

Images of cities as an expression of the identity of cultures and peoples are part of a memory file of the globalized world. These images are made up of consolidated stereotypes and new elements, in part resulting from film productions of various kinds and with different objectives.
This article discusses the cases of Granada and Lisbon through the first American travel movies dedicated to them (1920-1960), a genre of films that helped to create an 'image of the world' throughout much of the twentieth century. The context of the development of these film productions and
the partly common mechanisms they employed is addressed, shaping the global memory of these two emblematic cities of the Iberian peninsula.
The sad and painful news from Spain: Vatican relations with the Second Spanish Republic at the start of the Spanish Civil War, 1936
Authors: TRYBUS KARL J.
Published: January 2012

This article explores the relationship between the Holy See and the Second Spanish Republic during the first year of the Spanish Civil War - 1936. By exploring sources from the Secret Vatican Archives, a more complete understanding of this tenuous diplomatic relationship can be established.
The Holy See remained neutral during the conflict, but Republicans and Nationalists wanted to gain Vatican recognition to garner greater international support. The problem for the Republic was, however, that its unofficial militias lashed out against symbols of conservatism, especially members
of the Catholic Church. The Republic was angered that some Spanish Catholic clergymen had become outspoken supporters for the Nationalist rebellion against the government. The more radical actions of some followers helped to exacerbate the environment of confusion between the two states. This
article works to highlight locations where this confusion prevented the two states from understanding each other's opinions and actions.
Imagining relational violence: On taking a visual turn
Authors: Kosmala Katarzyna
Published: January 2012

The objective of this article is to problematize a notion of relational violence, also referred to as violence in domestic realms or relationship-based violence, drawing on its representation in the visual arts. The discussed examples illustrating the dynamics of violence include two American artists: Barbara Kruger's project organized in Glasgow in the Gallery of Modern Art in association with Amnesty International in 2005, and Bruce Nauman's video installations Anthro-Socio (1992) exhibited as part of his solo exhibition at Musee d'Art Contemporain in Montreal in 2007, and Violent Incident (1986) from the Tate Collection. Drawing on visual representation, I reflect on how different ways of narrating can either encourage or discourage our understandings of violence and the promotion of equality more generally. Framing the ways institutional power operates, here in relation to an organization of my academic role and other roles, involves a production and negotiation of meanings as well as embodiment. In such a context, reflections emerge with regard to my own positioning, concerning ambivalence about the politics of representation and the representation of the politics in the processes that are observed, analysed and showcased.
CONFERENCE REVIEW
Authors: Giesekam Greg
Published: January 2012

KNOWING WAYS, CRITICAL LEARNING IN PRACTICE CONFERENCE, NORTH EDINBURGH ARTS, MUIRHOUSE, EDINBURGH, 8–10 SEPTEMBER 2011
The Rett Syndrome Protein MeCP2 Regulates Synaptic Scaling
Authors: Qiu Zilong , Sylwestrak Emily L. , Lieberman David N. , Zhang Yan , Liu Xin-Yu , Ghosh Anirvan
Published: January 2012

Synaptic scaling is a form of homeostatic synaptic plasticity characterized by cell-wide changes in synaptic strength in response to changes in overall levels of neuronal activity. Here we report that bicuculline-induced increase in neuronal activity leads to a decrease in mEPSC amplitude and a decrease in expression of the AMPA receptor subunit GluR2 in rat hippocampal cultures. Bicuculline treatment also leads to an increase in the levels of the transcriptional repressor MeCP2, which binds to the GluR2 promoter along with the corepressors HDAC1 and mSin3A. Downregulation of MeCP2 by shRNA expression or genetic deletion blocks the bicuculline-induced decrease in GluR2 expression and mEPSC amplitude. These observations indicate that MeCP2 mediates activity-dependent synaptic scaling, and suggest that the pathophysiology of Rett syndrome, which is caused by mutations in MeCP2, may involve defects in activity-dependent regulation of synaptic currents.
Processing of Emotional Reactivity and Emotional Memory over Sleep
Authors: Baran Bengi , Pace-Schott Edward F. , Ericson Callie , Spencer Rebecca M. C.
Published: January 2012

Sleep enhances memories, particularly emotional memories. As such, it has been suggested that sleep deprivation may reduce posttraumatic stress disorder. This presumes that emotional memory consolidation is paralleled by a reduction in emotional reactivity, an association that has not yet been examined. In the present experiment, we used an incidental memory task in humans and obtained valence and arousal ratings during two sessions separated either by 12 h of daytime wake or 12 h including overnight sleep. Recognition accuracy was greater following sleep relative to wake for both negative and neutral pictures. While emotional reactivity to negative pictures was greatly reduced over wake, the negative emotional response was relatively preserved over sleep. Moreover, protection of emotional reactivity was associated with greater time in REM sleep. Recognition accuracy, however, was not associated with REM. Thus, we provide the first evidence that sleep enhances emotional memory while preserving emotional reactivity.
Maximal Variability of Phase Synchrony in Cortical Networks with Neuronal Avalanches
Authors: Yang Hongdian , Shew Woodrow L. , Roy Rajarshi , Plenz Dietmar
Published: January 2012

Ongoing interactions among cortical neurons often manifest as network-level synchrony. Understanding the spatiotemporal dynamics of such spontaneous synchrony is important because it may (1) influence network response to input, (2) shape activity-dependent microcircuit structure, and (3) reveal fundamental network properties, such as an imbalance of excitation (E) and inhibition (I). Here we delineate the spatiotemporal character of spontaneous synchrony in rat cortex slice cultures and a computational model over a range of differentE–Iconditions including disfacilitated (antagonized AMPA, NMDA receptors), unperturbed, and disinhibited (antagonized GABAAreceptors). Local field potential was recorded with multielectrode arrays during spontaneous burst activity. Synchrony among neuronal groups was quantified based on phase-locking among recording sites. As network excitability was increased from low to high, we discovered three phenomena at an intermediate excitability level: (1) onset of synchrony, (2) maximized variability of synchrony, and (3) neuronal avalanches. Our computational model predicted that these three features occur when the network operates near a unique balancedE–Icondition called “criticality.” These results were invariant to changes in the measurement spatial extent, spatial resolution, and frequency bands. Our findings indicate that moderate average synchrony, which is required to avoid pathology, occurs over a limited range ofE–Iconditions and emerges together with maximally variable synchrony. If variable synchrony is detrimental to cortical function, this is a cost paid for moderate average synchrony. However, if variable synchrony is beneficial, then by operating near criticality the cortex may doubly benefit from moderate mean and maximized variability of synchrony.