bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustained therapeutic hypercapnia attenuates pulmonary arterial Rho-kinase activity and ameliorates chronic hypoxic pulmonary hypertension in juvenile rats
Authors: Peng Gary , Ivanovska Julijana , Kantores Crystal , Van Vliet Todd , Engelberts Doreen , Kavanagh Brian P. , Enomoto Masahiro , Belik Jaques , Jain Amish , McNamara Patrick J. , Jankov Robert P.
Published: April 2012

Sustained therapeutic hypercapnia prevents pulmonary hypertension in experimental animals, but its rescue effects on established disease have not been studied. Therapies that inhibit Rho-kinase (ROCK) and/or augment nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling can reverse or prevent progression of chronic pulmonary hypertension. Our objective in the present study was to determine whether sustained rescue treatment with inhaled CO2(therapeutic hypercapnia) would improve structural and functional changes of chronic hypoxic pulmonary hypertension. Spontaneously breathing pups were exposed to normoxia (21% O2) or hypoxia (13% O2) from postnatal days 1–21 with or without 7% CO2(PaCO2elevated by ∼25 mmHg) or 10% CO2(PaCO2elevated by ∼40 mmHg) from days 14 to 21. Compared with hypoxia alone, animals exposed to hypoxia and 10% CO2had significantly ( P < 0.05) decreased pulmonary vascular resistance, right-ventricular systolic pressure, right-ventricular hypertrophy, and medial wall thickness of pulmonary resistance arteries as well as decreased lung phosphodiesterase (PDE) V, RhoA, and ROCK activity. Rescue treatment with 10% CO2, or treatment with a ROCK inhibitor (15 mg/kg ip Y-27632 twice daily from days 14 to 21), also increased pulmonary arterial endothelial nitric oxide synthase and lung NO content. In contrast, cGMP content and cGMP-dependent protein kinase (PKG) activity were increased by exposure to 10% CO2, but not by ROCK inhibition with Y-27632. In vitro exposure of pulmonary artery smooth muscle cells to hypercapnia suppressed serum-induced ROCK activity, which was prevented by inhibition of PKG with Rp-8-Br-PET-cGMPS. We conclude that sustained hypercapnia dose-dependently inhibited ROCK activity, augmented NO-cGMP-PKG signaling, and led to partial improvements in the hemodynamic and structural abnormalities of chronic hypoxic PHT in juvenile rats. Increased PKG content and activity appears to play a major upstream role in CO2-induced suppression of ROCK activity in pulmonary arterial smooth muscle.
Superiority of PC-SOD to other anti-COPD drugs for elastase-induced emphysema and alteration in lung mechanics and respiratory function in mice
Authors: Tanaka Ken-Ichiro , Sato Keizo , Aoshiba Kazutetsu , Azuma Arata , Mizushima Tohru
Published: April 2012

Bronchodilators (such as ipratropium bromide), steroids (such as fluticasone propionate), and newly developed anti-inflammatory drugs (such as roflumilast) are used for patients with chronic obstructive pulmonary disease (COPD). We recently reported that lecithinized superoxide dismutase (PC-SOD) confers a protective effect in mouse models of COPD. We here examined the therapeutic effect of the combined administration of PC-SOD with ipratropium bromide on pulmonary emphysema and compared the effect of PC-SOD to other types of drugs. The severity of emphysema in mice was assessed by various criteria. Lung mechanics (elastance) and respiratory function (ratio of forced expiratory volume in the first 0.05 s to forced vital capacity) were assessed. Administration of PC-SOD by inhalation suppressed elastase-induced pulmonary emphysema, alteration of lung mechanics, and respiratory dysfunction. The concomitant intratracheal administration of ipratropium bromide did not alter the ameliorating effects of PC-SOD. Administration of ipratropium bromide, fluticasone propionate, or roflumilast alone did not suppress the elastase-induced increase in the pulmonary level of superoxide anion, pulmonary inflammatory response, pulmonary emphysema, alteration of lung mechanics, or respiratory dysfunction as effectively as did PC-SOD. PC-SOD, but not the other drugs, showed a therapeutic effect even when the drug was administered after the development of emphysema. PC-SOD also suppressed the cigarette smoke-induced pulmonary inflammatory response and increase in airway resistance. Based on these results, we consider that the inhalation of PC-SOD would be therapeutically beneficial for COPD.
β-Adrenergic agonists differentially regulate highly selective and nonselective epithelial sodium channels to promote alveolar fluid clearance in vivo
Authors: Downs Charles A. , Kriener Lisa H. , Yu Ling , Eaton Douglas C. , Jain Lucky , Helms My N.
Published: April 2012

β-Adrenergic receptors (β-AR) increase epithelial sodium channel (ENaC) activity to promote lung fluid clearance. However, the effect of selective β-AR agonist on highly selective cation (HSC) channels or nonselective cation (NSC) channels in alveolar type 1 (T1) and type 2 (T2) cells is unknown. We hypothesized that stimulation with β1-AR agonist (denopamine) or β2-AR agonist (terbutaline) would increase HSC and/or NSC channel activity in alveolar epithelial cells. We performed single-channel measurements from T1 and T2 cells accessed from rat lung slices. Terbutaline (20 μM) increased HSC ENaC activity (open probability, NPo) in T1 (from 0.96 ± 0.61 to 1.25 ± 0.71, n = 5, P <0.05) and T2 cells (from 0.28 ± 0.14 to 1.0 ± 0.30, n = 8, P = 0.02). Denopamine (20 μM) increased NSC NPo in T1 cells (from 0.34 ± 0.09 to 0.63 ± 0.14, n = 7, P = 0.02) and in T2 cells (from 0.47 ± 0.09 to 0.68 ± 0.10, P = 0.004). In vivo X-ray imaging of lung fluid clearance and ICI 118,551 selective inhibition of β2-ARs confirmed patch-clamp findings. cAMP concentrations increased following treatment with denopamine or terbutaline ( n = 3, P < 0.002). The effects of systemic (intraperitoneal, IP) and local (intratracheal, IT) modes of delivery on lung fluid clearance were assessed. IT delivery of denopamine promoted alveolar flooding, whereas IP delivery promoted delayed fluid clearance. In summary, β-AR agonists differentially regulate HSC and NSC in T1 and T2 cells to promote lung fluid clearance in vivo, and the mode of drug delivery is critical for maximizing β-AR agonist efficacy.
RAGE signaling by alveolar macrophages influences tobacco smoke-induced inflammation
Authors: Robinson Adam B. , Johnson KacyAnn D. , Bennion Brock G. , Reynolds Paul R.
Published: April 2012

Receptors for advanced glycation end-products (RAGE) are multiligand cell surface receptors of the immunoglobin family expressed by epithelium and macrophages, and expression increases following exposure to cigarette smoke extract (CSE). The present study sought to characterize the proinflammatory contributions of RAGE expressed by alveolar macrophages (AMs) following CSE exposure. Acute exposure of mice to CSE via nasal instillation revealed diminished bronchoalveolar lavage (BAL) cellularity and fewer AMs in RAGE knockout (KO) mice compared with controls. Primary AMs were obtained from BAL, exposed to CSE in vitro, and analyzed. CSE significantly increased RAGE expression by wild-type AMs. Employing ELISAs, wild-type AMs exposed to CSE had increased levels of active Ras, a small GTPase that perpetuates proinflammatory signaling. Conversely, RAGE KO AMs had less Ras activation compared with wild-type AMs after exposure to CSE. In RAGE KO AMs, assessment of p38 MAPK and NF-κB, important intracellular signaling intermediates induced during an inflammatory response, revealed that CSE-induced inflammation may occur in part via RAGE signaling. Lastly, quantitative RT-PCR revealed that the expression of proinflammatory cytokines including TNF-α and IL-1β were detectably decreased in RAGE KO AMs exposed to CSE compared with CSE-exposed wild-type AMs. These results reveal that primary AMs orchestrate CSE-induced inflammation, at least in part, via RAGE-mediated mechanisms.
Renal interstitial hyaluronan: functional aspects during normal and pathological conditions
Authors: Stridh Sara , Palm Fredrik , Hansell Peter
Published: April 2012

The glycosaminoglycan (GAG) hyaluronan (HA) is recognized as an important structural component of the extracellular matrix, but it also interacts with cells during embryonic development, wound healing, inflammation, and cancer; i.e., important features in normal and pathological conditions. The specific physicochemical properties of HA enable a unique hydration capacity, and in the last decade it was revealed that in the interstitium of the renal medulla, where the HA content is very high, it changes rapidly depending on the body hydration status while the HA content of the cortex remains unchanged at very low amounts. The kidney, which regulates fluid balance, uses HA dynamically for the regulation of whole body fluid homeostasis. Renomedullary HA elevation occurs in response to hydration and during dehydration the opposite occurs. The HA-induced alterations in the physicochemical characteristics of the interstitial space affects fluid flux; i.e., reabsorption. Antidiuretic hormone, nitric oxide, angiotensin II, and prostaglandins are classical hormones/compounds involved in renal fluid handling and are important regulators of HA turnover during variations in hydration status. One major producer of HA in the kidney is the renomedullary interstitial cell, which displays receptors and/or synthesis enzymes for the hormones mentioned above. During several kidney disease states, such as ischemia-reperfusion injury, tubulointerstitial inflammation, renal transplant rejection, diabetes, and kidney stone formation, HA is upregulated, which contributes to an abnormal phenotype. In these situations, cytokines and other growth factors are important stimulators. The immunosuppressant agent cyclosporine A is nephrotoxic and induces HA accumulation, which could be involved in graft rejection and edema formation. The use of hyaluronidase to reduce pathologically overexpressed levels of tissue HA is a potential therapeutic tool since diuretics are less efficient in removing water bound to HA in the interstitium. Although the majority of data describing the role of HA originate from animal and cell studies, the available data from humans demonstrate that an upregulation of HA also occurs in diabetic kidneys, in transplant-rejected kidneys, and during acute tubular necrosis. This review summarizes the current knowledge regarding interstitial HA in the role of regulating kidney function during normal and pathological conditions. It encompasses mechanistic insights into the background of the heterogeneous intrarenal distribution of HA; i.e., late nephrogenesis, its regulation during variations in hydration status, and its involvement during several pathological conditions. Changes in hyaluronan synthases, hyaluronidases, and binding receptor expression are discussed in parallel.
Meal-contingent intestinal lymph sampling from awake, unrestrained rats
Authors: Arnold Myrtha , Dai Yunting , Tso Patrick , Langhans Wolfgang
Published: April 2012

Standard procedures for intestinal lymph collection involve continuous, quantitative drainage of the lymph fluid in anesthetized or restrained animals that are often euthanized within 48 h. We here describe a novel technique for the nonocclusive cannulation of the major intestinal lymph duct in rats that allows for repetitive in vivo sampling of intestinal lymph from unrestrained, awake, and ad libitum-fed animals. The distinctive feature of this novel technique is that a 5- to 7-mm long piece of Vialon tubing (OD/ID: 0.8/0.7 mm) with a small hole in its wall is first implanted into the major intestinal lymph duct for stabilization. The tapered tip (OD: ≈0.1 mm) of the catheter is then inserted into the hole of the tubing and fixed in place with a polyamid suture and a drop of tissue glue. In our hands, catheters implanted this way remain patent for up to 6 wk after surgery. In an initial experiment we collected lymph from six adult rats before (0) and 15, 30, 45, 60, 75, 90, 120, and 180 min (120 μl, each) after the onset of isocaloric (12.5 kcal) low-fat (LF) or high-fat (HF) test meals and measured active glucagon-like peptide-1 (GLP-1). Intestinal lymphatic GLP-1 concentration increased ( P < 0.05) from ≈4 pmol/l (0 min) to a peak of 33 ± 6 (means ± SE) or 22 ± 4 pmol/l at 15 (HF) or 30 min (LF) after meal onset and gradually returned to baseline levels by 180 min. With this new technique fewer animals are required to generate physiologically relevant data for various aspects of gastrointestinal physiology that involve the lymphatic system. Furthermore, the advantage of this system is that the animal can act as its own control when the effect of different experimental protocols is tested.
A Review on the Use of Confocal Laser Endomicroscopy in the Bile Duct
Authors: Smith Ioana , Kline Pamela E. , Gaidhane Monica , Kahaleh Michel
Published: April 2012

Background. Current methods to diagnose malignant biliary strictures are of low sensitivity. Probe-based confocal laser endomicroscopy (pCLE) is a new approach that can be used to evaluate in vivo histopathology of the GI tract. This paper is of studies evidencing pCLE’s application in the diagnosis of indeterminate biliary strictures.Methods. This paper examined peer-reviewed studies conducted between January 2000 and November 2011. A PubMed search for relevant articles was performed using the following keywords:“pCLE”, “confocal”, “endomicroscopy”, “probe-based confocal laser endomicroscopy”, “and “bile duct”. Further individual review was done to assess the screened articles’ relevance to the topic.Results. After individual review, 6 studies were included; with a cumulative sample size of 165, with 75 subjects identified as having a malignancy. These studies included tertiary care centers in Germany, France, and USA, including one multicenter trial. 3 studies assessed pCLE’s specificity (range 67%–88%) ,sensitivity (range 83%–98), and accuracy (range 81%–86%).Conclusion. Confocal endomicroscopy is a novel and promising modality for the biliary tree. Further studies need to be conducted both to establish its usefulness for the diagnosis of indeterminate biliary strictures and to understand the histological meaning of the imaging patterns that are observed.
Cell-Mediated Autophagy Promotes Cancer Cell Survival
Authors: Buchser William J. , Laskow Thomas C. , Pavlik Philip J. , Lin Hui-Min , Lotze Michael T.
Published: April 2012

Immune effector cells integrate signals that define the nature and magnitude of the subsequent response. Experimental measures for immune cell–mediated lysis of tumors or virally infected targets rely on average responses of permeability or apoptotic changes within a population of targets. Here, we examined individual target cells following interaction with lymphoid effectors. We found that human peripheral blood lymphocytes not only provide lytic signals but also promote autophagy in the remaining cells. At high effector-to-target ratios, autophagy was induced in several human tumors, as assessed by induction of LC3 puncta and diminished p62. Natural killer cells are a primary mediator of this process. In addition, target cell autophagy was enhanced by provision of interleukin (IL)-2, whereas IL-10 attenuated this effect, and cell-to-cell contact strongly enhanced lymphocyte-mediated autophagy. Although IFN-γ can induce autophagy in target cells, IFN-α acted directly on the targets or in concert with lymphocytes to diminish target autophagy in some cell types. Importantly, cell-mediated autophagy promoted resistance from treatment modalities designed to eradicate tumor cells. Our findings therefore show that the lymphocyte-induced cell-mediated autophagy promotes cancer cell survival and may represent an important target for development of novel therapies. Cancer Res; 72(12); 2970–9. ©2012 AACR.
ESE3/EHF Controls Epithelial Cell Differentiation and Its Loss Leads to Prostate Tumors with Mesenchymal and Stem-like Features
Authors: Albino Domenico , Longoni Nicole , Curti Laura , Mello-Grand Maurizia , Pinton Sandra , Civenni Gianluca , Thalmann George , D'Ambrosio Gioacchino , Sarti Manuela , Sessa Fausto , Chiorino Giovanna , Catapano Carlo V. , Carbone Giuseppina M.
Published: April 2012

Cancer stem cells (CSC) play a significant role in tumor progression, disease recurrence, and treatment failure. Here, we show that the endogenously expressed ETS transcription factor ESE3/EHF controls prostate epithelial cell differentiation and stem-like potential. We found that loss of ESE3/EHF induced epithelial-to-mesenchymal transition (EMT), stem-like features, and tumor-initiating and metastatic properties in prostate epithelial cells, and reexpression of ESE3/EHF inhibited the stem-like properties and tumorigenic potential of prostate cancer cells. Mechanistically, ESE3/EHF repressed the expression of key EMT and CSC genes, including TWIST1, ZEB2, BMI1, and POU5F1. Analysis of human tissue microarrays showed that reduced ESE3/EHF expression is an early event in tumorigenesis, frequently occurring independently of other ETS gene alterations. Additional analyses linked loss of ESE3/EHF expression to a distinct group of prostate tumors with distinctive molecular and biologic characteristics, including increased expression of EMT and CSC genes. Low ESE3/EHF expression was also associated with increased biochemical recurrence of prostate cancer and reduced overall survival after prostatectomy. Collectively, our findings define a key role for ESE3/EHF in the development of a subset of prostate tumors and highlight the clinical importance of identifying molecularly defined tumor subgroups. Cancer Res; 72(11); 2889–900. ©2012 AACR.
Analysis of Fcγ Receptor IIIa and IIa Polymorphisms: Lack of Correlation with Outcome in Trastuzumab-Treated Breast Cancer Patients
Authors: Hurvitz Sara A. , Betting David J. , Stern Howard M. , Quinaux Emmanuel , Stinson Jeremy , Seshagiri Somasekar , Zhao Ying , Buyse Marc , Mackey John , Driga Adrian , Damaraju Sambasivarao , Sliwkowski Mark X. , Robert Nicholas J. , Valero Vicente , Crown John , Falkson Carla , Brufsky Adam , Pienkowski Tadeusz , Eiermann Wolfgang , Martin Miguel , Bee Valerie , Marathe Omkar , Slamon Dennis J. , Timmerman John M.
Published: April 2012

Purpose: The mechanisms by which trastuzumab imparts clinical benefit remain incompletely understood. Antibody-dependent cellular cytotoxicity via interactions with Fcγ receptors (FcγR) on leukocytes may contribute to its antitumor effects. Single-nucleotide polymorphisms (SNP) in FCGR3A and FCGR2A genes lead to amino acid substitutions at positions 158 and 131, respectively, and affect binding of antibodies to FcγR such that 158V/V and 131H/H bind with highest affinity. This study aimed to determine whether high-affinity SNPs are associated with disease-free survival (DFS) among patients with HER2-positive nonmetastatic breast cancer.

Experimental Design: Genomic DNA was isolated from 1,286 patients enrolled in a trial of adjuvant trastuzumab-based chemotherapy. Genotyping was conducted using Sanger sequencing and Sequenom mass spectrometry.

Results: Patient samples (N = 1,189) were successfully genotyped for FCGR3A and 1,218 for FCGR2A. Compared with the overall results of the BCIRG006 study, in the subset of patients genotyped in this analysis, a less robust improvement in DFS was observed for the trastuzumab arms than control arm (HR, 0.842; P = 0.1925). When stratified for prognostic features, the HR in favor of trastuzumab was consistent with that of the overall study (HR, 0.74; P = 0.036). No correlation between DFS and FCGR3A/2A genotypes was seen for trastuzumab-treated patients (158V/V vs. V/F vs. F/F, P = 0.98; 131H/H vs. H/R vs. R/R, P = 0.76; 158V/V and/or 131H/H vs. others, P = 0.67).

Conclusion: This analysis evaluating the association between FCGR3A/2A genotypes and trastuzumab efficacy in HER2-positive breast cancer did not show a correlation between FCGR3A-V/F and FCGR2A-H/R SNPs and DFS in patients treated with trastuzumab. Clin Cancer Res; 18(12); 3478–86. ©2012 AACR.
A Cohort Study on the Association of Early Mutans Streptococci Colonisation and Dental Decay
Authors: Laitala M. , Alanen P. , Isokangas P. , Söderling E. , Pienihäkkinen K.
Published: April 2012

In children, a strong relationship between the timing of colonisation of mutans streptococci (MS) and future caries risk has been shown to exist. The aim of the study was to examine the association of early MS colonisation with dental decay and the need for restorative treatment. The subjects had been participants in an earlier Finnish mother-child study and assumed to be high-caries-risk subjects due to their mothers’ high MS levels. The information on MS colonisation at 2 years of age was available for 164 children. Of them, comprehensive data on dental health, visits and treatments until 10 years of age were found in the registers for 147 subjects. The children who had not been colonised by MS at 2 years of age (n = 118) maintained their teeth caries-free longer than the MS-colonised (n = 29) children. The median value for the caries-free time for MS-colonised children was 4.6 years, in comparison with 8.0 years for non-MS-colonised children (p < 0.001, hazard ratio 2.70; 95% CI 1.72–4.25, Cox regression). Until 10 years of age, the MS-colonised children had made on average 4.6 visits for restorative treatment, while the non-MS-colonised had made 2.8 visits (p = 0.005, Student’s t test). The results suggest that the avoided early MS colonisation may lead to favourable long-term effects on caries experience and need for restorative treatment.
A Common Variant in the
PTPN11
Gene Contributes to the Risk of Tetralogy of Fallot
Authors: Goodship Judith A. , Hall Darroch , Topf Ana , Mamasoula Chrysovalanto , Griffin Helen , Rahman Thahira J. , Glen Elise , Tan Huay , Palomino Doza Julian , Relton Caroline L. , Bentham Jamie , Bhattacharya Shoumo , Cosgrove Catherine , Brook David , Granados-Riveron Javier , Bu'Lock Frances A. , O'Sullivan John , Stuart A. Graham , Parsons Jonathan , Cordell Heather J. , Keavney Bernard
Published: April 2012

Background—

Tetralogy of Fallot (TOF) is the commonest cyanotic form of congenital heart disease. In 80% of cases, TOF behaves as a complex genetic condition exhibiting significant heritability. As yet, no common genetic variants influencing TOF risk have been robustly identified.

Methods and Results—

Two hundred and seven haplotype-tagging single nucleotide polymorphisms in 22 candidate genes were genotyped in a test cohort comprising 362 nonsyndromic British white patients with TOF together with 717 unaffected parents of patients and 183 unrelated healthy controls. Single nucleotide polymorphisms with suggestive evidence of association in the test cohort (
P
<0.01) were taken forward for genotyping in an independent replication cohort comprising 392 cases of TOF, 218 unaffected parents of patients, and 1319 controls. Significant association was observed for 1 single nucleotide polymorphism, rs11066320 in the
PTPN11
gene, in both the test and the replication cohort. Genotype at rs11066320 was associated with a per-allele odds ratio of 1.34 (95% confidence interval [CI], 1.19 to 1.52;
P
=2.9×10
−6
) in the total cohort of TOF cases and controls; this remained highly significant after Bonferroni correction for 207 analyses (corrected
P
=0.00061). Genotype at rs11066320 was responsible for a population-attributable risk of TOF of approximately 10%.

Conclusions—

Common variation in the linkage disequilibrium block including the
PTPN11
gene contributes to the risk of nonsyndromic TOF. Rare mutations in
PTPN11
are known to cause the autosomal dominant condition Noonan syndrome, which includes congenital heart disease, by upregulating Ras/mitogen-activated protein kinase (MAPK) signaling. Our results suggest a role for milder perturbations in
PTPN11
function in sporadic, nonsyndromic congenital heart disease.
Warming of Western North Pacific Ocean and Energetics of Transient Eddy Activity
Authors: Heo Ki-Young , Ha Kyung-Ja , Lee Sun-Seon
Published: April 2012

This study examines the increase in the sea surface temperature (SST) in the western North Pacific Ocean (WNPO) during December–February for the period 1959–2008. The relationship of this SST increase with significant interdecadal changes in the baroclinicity and the energetics of transient eddy activity is also examined. These results show that the interannual variations of the WNPO SST and atmospheric conditions including baroclinicity and turbulent heat flux are responses to the upstream atmospheric forcings associated with the East Asian winter monsoon (EAWM). For the interdecadal variations, the intensified baroclinicity downstream of the Pacific storm-track activity is responsible for an increase in the baroclinic energy conversion (BCEC) from the mean available potential energy (MAPE) to the eddy available potential energy (EAPE) to the east of 180°. This in turn increases the BCEC from the EAPE to the eddy kinetic energy (EKE) over this region. The BCEC and generation of EAPE by diabatic heating are enhanced to the east of 180° as a result of the intensified baroclinicity. This could be responsible for the development of transient eddy activity downstream of the Pacific storm track over the North Pacific.
High-Skilled Migrants
Authors: Martin Philip
Published: April 2012

Universities and employers want easier access to foreign science and engineering (S&E) students and workers. Most U.S. residents with degrees in S&E fields are U.S.-born citizens, and there are far more U.S. citizens with S&E degrees, about 15 million, than are employed in S&E occupations, about 5 million. Foreign students and workers in S&E occupations are concentrated in computer-related jobs, and their presence raises trade-offs for U.S. students and workers. For example, making it easier for U.S. employers to hire foreign S&E workers allows employers to specify precisely the qualities desired to fill a particular job quickly while limiting options for U.S. workers who could fill that job with some retraining. This article reviews the trade-offs between the competing goods raised by foreign S&E students and workers and the efforts of U.S. government agencies to reconcile them.
Reading the New Testament Household Codes in Light of New Research on Children and Childhood in the Roman World
Authors: MacDonald Margaret Y.
Published: April 2012

The references to children and the child–parent relationship in the New Testament household codes (Col 3:20–21; Eph 6:1–4) have received little attention from scholars. Yet recent, cross-disciplinary interest in the study of children and childhood invites us to consider these exhortations afresh. In particular, current research in Roman Family Studies has led to greater appreciation of the multifaceted circumstances of children, raising new questions about the children who were addressed directly in the household codes of Colossians and Ephesians. Two themes are especially important to consider: (1) overlapping categories of identity tied especially to the complex structures of a slave-holding society; and (2) the household as a locus for education throughout the life course. Informed by current research on children and childhood, the household codes appear to be even more significant than was previously thought for understanding the place of house churches in the Roman imperial world.

Les références aux enfants et la relation parent-enfant dans les codes domestiques du Nouveau Testament (Col 3.20–21; Ép 6.1–4) ont reçu peu d’attention des chercheurs. Pourtant, récemment, l’intérêt interdisciplinaire dans l’étude des enfants et de l’enfance nous invite à reconsidérer ces exhortations. En particulier, la recherche actuelle en études familiales romaines a conduit à une plus grande appréciation de la situation des enfants à multiples facettes, ce qui soulève de nouvelles questions sur les enfants qui ont été adressées directement dans les codes domestiques de Colossiens et Ephésiens. Deux thèmes sont particulièrement importants à considérer: (1) catégories qui se recoupent d’identité liée en particulier aux structures complexes d’une société esclavagiste, et (2) la maison comme un lieu d’éducation tout au long du cycle de la vie. Informé par la recherche actuelle sur les enfants et l’enfance, les codes domestiques semblent être encore plus importants qu’on ne le pensait pour comprendre la place des églises de maison dans le monde romain impérial.
Respect and agency: An empirical exploration
Authors: Schirmer Werner , Weidenstedt Linda , Reich Wendelin
Published: April 2012

Both in social science and in everyday life, ‘respect’ is an important and widely used term to describe positive conduct of one person towards another. However, just what respectful behaviour refers to, and how it can be differentiated from considerate, tolerant, kind, etc. behaviour continues to elude social-scientific analysis. In order to investigate the meaning that people give to the concept of respect, the authors carried out focus groups in that participants discussed two vignettes regarding respect and a very closely related concept – considerateness. A systematic analysis of the transcripts preliminary supported the study’s hypothesis that respect is a form of behaviour which refers to the ascribed agency of another person, as opposed to non-agential properties such as needs or feelings.
The Impact of Human Rights Organizations on Naming and Shaming Campaigns
Authors: Meernik James , Aloisi Rosa , Sowell Marsha , Nichols Angela
Published: April 2012

Given the myriad of human rights abuses that occur globally and daily, why are some nations on the receiving end of a substantial amount of international opprobrium, while others receive far less attention and condemnation? The authors contend that the increasing presence of human rights organizations in such states is the critical link between the local and the international. Increases in the number of such groups contributes significantly to the generation of Amnesty International urgent actions, one of the most-often-utilized tools in naming and shaming campaigns against human rights abusing regimes. The authors find strong support for nearly all their hypotheses.
Economic Expectations, Optimistic Bias, and Television Viewing During Economic Recession
Authors: Hetsroni Amir , Sheaffer Zachary , Ben Zion Uri , Rosenboim Mosi
Published: April 2012

We examine the relationship between TV viewing and economic expectations during economic recession. A content analysis of 84 hours of local network primetime programming (news and nonnews) identifies a moderate bias toward economic pessimism in the broadcasts. A survey of the adult population ( N = 356) points at a significant positive relationship between TV viewing (total viewing and viewing of news programming) and economic pessimism at both the national and the personal levels. A similar relationship exists between TV viewing and optimistic bias—the tendency to be more pessimistic on economic matters at the national than at the personal level. These results remain significant when controlled for demographics, trust in national institutions, evaluation of current economic situation and consumption of media other than TV, and corroborate a second-order cultivation effect in the economic context.
Factor Structure of the Bumby RAPE Scale
Authors: Hermann Chantal A. , Babchishin Kelly M. , Nunes Kevin L. , Leth-Steensen Craig , Cortoni Franca
Published: April 2012

Rape-supportive cognition is both theoretically and empirically related to rape. Several types of rape-supportive cognition (cognitive distortions) have been identified in the literature, suggesting that rapists’ rape-supportive cognition may be multidimensional. The Bumby RAPE Scale is one measure of rape-supportive cognition. The authors conducted an exploratory factor analysis using polychoric correlations to examine the types of rape-supportive cognition assessed by the Bumby RAPE Scale with a sample of 280 adult male sex offenders. A two-factor model was found; the two factors were labeled Excusing Rape and Justifying Rape. The current study suggests that the Bumby RAPE Scale is multidimensional. This factor structure may provide greater precision and clarity in the assessment of rape-supportive cognition, which may facilitate more informative research and, ultimately, contribute to more effective sex offender treatment and management.
Arab Uprisings, Armed Forces, and Civil–Military Relations
Authors: Lutterbeck Derek
Published: April 2012

Since late 2010, an unprecedented wave of protests demanding greater political freedoms, and in several countries even regime change, has swept across much of the Arab world. In Tunisia, Egypt, and Libya, long-standing autocrats have been toppled, and in other countries of the region seemingly well-established authoritarian regimes also appeared increasingly shaky in the face of growing opposition movements. The aim of this article is to examine the role of the armed forces in these popular uprisings. While military forces have been key actors in these Arab uprisings, they have responded quite differently across the region to prodemocracy movements, ranging from openness to protest movements, to internal fracturing, to firm support for the regime in power. This article argues that these differences can be explained with reference to different forms of civil–military relations and different characteristics of the military apparatus. It claims in particular that the degree of institutionalization of the armed forces and their relationship to society at large can account for the divergent responses to pro-reform movements.
The Effect of an Enrichment Program on Developing Analytical, Creative, and Practical Abilities of Elementary Gifted Students
Authors: Aljughaiman Abdullah M. , Ayoub Alaa Eldin A.
Published: April 2012

The current study investigated the effects of a school enrichment program on the analytical, creative, and practical abilities of elementary gifted students. Forty-two students ( N = 42) from the fifth and sixth grade of the Al-Shawkany School in Saudi Arabia were randomly chosen to participate in the study according to two criteria: (a) being among the top 5% on the general ability test designed for the Saudi environment and (b) a general studies achievement test score of 90% to 100%. The enrichment program lasted 6 weeks. The Aurora Battery was administered to the participants at the beginning as well as at the end of the program. The Mann-Whitney U test for independent groups yielded statistically significant differences between the medians of the experimental and control groups in analytical and creative abilities in favor of the experimental group. There were no statistically significant differences in the practical abilities and the total score. Results of the Wilcoxon Signed-Rank Test showed that there were statistically significant differences between the medians of the experimental group on pretest and posttest of the analytical and creative abilities, whereas there were no statistically significant differences in practical abilities and in the total score. A multivariate Kruskal–Wallis test revealed that there were significant differences among the three abilities in favor of analytical abilities.
Measuring presidential powers: Some pitfalls of aggregate measurement
Authors: Fortin Jessica
Published: April 2012

The purpose of this article is to address the issues of validity and reliability in existing additive indices measuring the strength of executives. Many data efforts, such as Frye et al. (2000) as well as Armingeon and Careja (2007), propose indices of presidential power based on a simple accumulation of a set of individual constitutional prerogatives allotted to the head of state according to the design proposed by Shugart and Carey (1992). These indices usually gather and count the powers of presidents on package and partial vetoes, decrees, budgetary powers, referenda provisions, initiation of legislation, cabinet formation, cabinet dismissal, censure, and the dissolution of assemblies. Despite the general acceptance of such measures of presidential power and their widespread use, empirical investigations to ascertain the degree to which existing indices measure a single latent construct, and are valid and reliable, were never conducted. In this article, I refute the assumptions of unimodality and unidimensionality underlying these indices, and challenge their usefulness in allowing researchers to differentiate between presidential, semi-presidential, and parliamentary institutional arrangements.
From state feminism to market feminism?
Authors: Kantola Johanna , Squires Judith
Published: April 2012

This article argues that the concept of ‘state feminism’ no longer adequately captures the complexity of emerging feminist engagements with new forms of governance. It suggests that ‘market feminism’ offers a new conceptual framework from which feminist engagements with the state can be analysed and evaluated, and the changes within state feminism can be understood. The article documents the growing feminist embrace of the logic of the market, which manifests itself in changed practices and priorities. The article gives examples of ‘market feminism’ and argues that the move from state feminism to market feminism impacts on both the political practices and policy priorities of women’s policy agencies.
Dialogue or compliance? Measuring legislatures’ policy responses to court rulings on rights
Authors: Macfarlane Emmett
Published: April 2012

There is a growing consensus that parliamentary systems with recently enacted bills of rights constitute a new model of constitutionalism that serves as a middle ground between parliamentary sovereignty and judicial supremacy. One of the key features often discussed in relation to this ‘weak-form’ or ‘Commonwealth’ model of judicial review is the notion of an inter-branch dialogue about rights that permits legislatures to respond to court rulings about the policies at stake. This article develops a framework for empirically assessing whether and how dialogue operates in practice. A systematic examination of legislative responses to Supreme Court rulings affecting legislation in Canada finds that relatively little genuine dialogue occurs in practice because legislatures rarely respond in a manner that departs from the dictates of the Court’s rulings. The article then explores the implications this type of empirical assessment might have for other parliamentary systems.
The Development of Subcutaneous Sarcomas in Rodents Exposed to Peroxisome Proliferators Agonists
Authors: Pruimboom-Brees Ingrid M. , Francone Omar , Pettersen John C. , Kerlin Roy L. , Will Yvonne , Amacher David E. , Boucher Germaine G. , Morton Daniel
Published: April 2012

Peroxisome proliferator-activated receptors (PPARs) represent therapeutic targets for the management of type 2 diabetes mellitus and dyslipidemia. Rodent carcinogenicity studies have revealed a link between γ and dual γ/α PPAR agonist treatment and the increased incidence of subcutaneous (SC) liposarcomas/fibrosarcomas or hemangiosarcomas, but very little has been reported for potent and selective PPARα agonists. We present a mode of action framework for the development of SC mesenchymal tumors in rodents given PPAR agonists. (1) Tumor promotion results from pharmacologically mediated recruitment (proliferation and differentiation), thermogenesis and adipogenesis of stromovascular cells, and subsequent generation of oxidative free radicals. (2) Tumor initiation consists of chemotype-driven mitochondrial dysfunction causing uncontrolled oxidative stress and permanent DNA damage. Promotion is characterized by enhanced adipogenesis in the SC adipose tissue, where the baseline PPARγ expression and responsiveness to PPARγ ligands is the highest, and by thermogenesis through expression of the uncoupling protein 1 (UCP-1) and the PPARγ co-activator 1 α (PGC-1α), two factors more highly expressed in brown versus white adipose tissue. Initiation is supported by the demonstration of mitochondrial uncoupling and OXPHOS Complexes dysfunction (Complexes III, IV and V) by compounds associated with increased incidences of sarcomas (muraglitazar and troglitazone), but not others lacking malignant tumor effects (pioglitazone, rosiglitazone).
Magnetic Resonance Histology of Age-Related Nephropathy in the Sprague Dawley Rat
Authors: Xie Luke , Cianciolo Rachel E. , Hulette Brian , Lee Ha Won , Qi Yi , Cofer Gary , Johnson G. Allan
Published: April 2012

Magnetic resonance histology (MRH) has become a valuable tool in evaluating drug-induced toxicity in preclinical models. However, its application in renal injury has been limited. This study tested the hypothesis that MRH could detect image-based biomarkers of chronic disease, inflammation, or age-related degeneration in the kidney, laying the foundation for more extensive use in evaluating drug toxicity. We examined the entire intact kidney in a spontaneous model of chronic progressive nephropathy. Kidneys from male Sprague Dawley rats were imaged at 8 weeks ( n = 4) and 52 weeks ( n =4) on a 9.4 T system dedicated to MR microscopy. Several potential contrast mechanisms were explored to optimize the scanning protocols. Full coverage of the entire kidney was achieved with isotropic spatial resolution at 31 microns (voxel volume = 30 pL) using a gradient recalled echo sequence. Isotropic spatial resolution of 15 microns (voxel volume < 4 pL) was achieved in a biopsy core specimen. Qualitative age-related structural changes, such as renal cortical microvasculature, tubular dilation, interstitial fibrosis, and glomerular architecture, were apparent. The nondestructive 3D images allowed measurement of quantitative differences of kidney volume, pelvis volume, main vessel volume, glomerular size, as well as thickness of the cortex, outer medulla, and inner medulla.
Class Attendance and Students’ Evaluations of Teaching
Authors: Wolbring Tobias
Published: April 2012

Background: Many university departments use students’ evaluations of teaching (SET) to compare and rank courses. However, absenteeism from class is often nonrandom and, therefore, SET for different courses might not be comparable. Objective: The present study aims to answer two questions. Are SET positively biased due to absenteeism? Do procedures, which adjust for absenteeism, change course rankings? Research Design: The author discusses the problem from a missing data perspective and present empirical results from regression models to determine which factors are simultaneously associated with students’ class attendance and course ratings. In order to determine the extent of these biases, the author then corrects average ratings for students’ absenteeism and inspect changes in course rankings resulting from this adjustment. Subjects: The author analyzes SET data on the individual level. One or more course ratings are available for each student. Measures: Individual course ratings and absenteeism served as the key outcomes. Results: Absenteeism decreases with rising teaching quality. Furthermore, both factors are systematically related to student and course attributes. Weighting students’ ratings by actual absenteeism leads to mostly small changes in ranks, which follow a power law. Only a few, average courses are disproportionally influenced by the adjustment. Weighting by predicted absenteeism leads to very small changes in ranks. Again, average courses are more strongly affected than courses of very high or low in quality. Conclusions: No-shows bias course ratings and rankings. SET are more appropriate to identify high- and low-quality courses than to determine the exact ranks of average courses.
The Interactive Role of Socioeconomic Status, Race/Ethnicity, and Birth Weight on Trajectories of Body Mass Index Growth in Children and Adolescents
Authors: Danner Fred W. , Toland Michael D.
Published: April 2012

This study assessed how socioeconomic status (SES), race/ethnicity, and birth weight interacted to predict differential patterns of body mass index (BMI) growth among U.S. children born in the early 1990s. Three BMI growth trajectories emerged—one above the 50th percentile across the age range of 5 to 14, one in which children rapidly became obese before adolescence, and one where children started out and remained seriously obese. Hispanic and African American children were more likely to show accelerated patterns of weight gain as were those of lower SES and/or higher birth weights. However, SES interacted with both race/ethnicity and birth weight. For girls of all race/ethnicity groups tested, lower SES and higher birth weights predicted membership in the seriously obese BMI growth trajectory. For African American and Asian boys, however, the higher the SES the more likely they were to be on a trajectory for rapidly developing obesity by early adolescence.
Why Do Bystanders of Bullying Help or Not? A Multidimensional Model
Authors: Pozzoli Tiziana , Gini Gianluca
Published: April 2012

The authors employed Latanè and Darley’s model about bystanders’ behavior to explain children’s active defending and passive bystanding behavior in school bullying. The three central steps of the model were operationalized by measuring provictim attitudes, personal responsibility for intervention, and coping strategies. Moreover, the role of perceived expectations from parents and peers was investigated. A total of 759 children and 995 early adolescents participated. The findings from structural equation modeling (SEM) confirmed the hypothesized relationships and the impact of perceived peer and parent pressure on nearly all the study variables. The model was confirmed for both age groups, with only a few differences in the paths’ magnitudes, and the model demonstrated the importance of considering both strictly individual characteristics and contextual variables. These results substantially expand previous findings and have potential interest for both researchers and educators.
Cambodian Early Adolescents’ Academic Achievement
Authors: Eng Sothy
Published: April 2012

This study examined the associations of parents’ cultural beliefs and attitudes with respect to fate, traditional gender roles, aspirations, and involvement in children’s academic achievement in Cambodia. Based on Coleman’s social capital theory, a good parent-child relationship enables children’s school success because resources are created as a result of the children’s recognizing the value their parents place on education. Samples included 202 parent-child dyads. Results showed that greater students’ academic achievement was predicted by lower parents’ fatalistic beliefs and longer length of residence. Parents’ gender role attitudes indirectly predicted academic achievement via extra class hours for only girls. However, parents’ academic involvement and aspirations often associated with academic achievement among children in North America were not similarly associated in this study, raising the question of cultural specificity of these variables in other places in the world. The results suggest the importance of studying child development in specific cultural contexts.