bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal separation produces lasting changes in cortisol and behavior in rhesus monkeys
Authors: Feng Xiaoli , Wang Lina , Yang Shangchuan , Qin Dongdong , Wang Jianhong , Li Chunlu , Lv Longbao , Ma Yuanye , Hu Xintian
Published: August 2011

Maternal separation (MS), which can lead to hypothalamic pituitary adrenal axis dysfunction and behavioral abnormalities in rhesus monkeys, is frequently used to model early adversity. Whether this deleterious effect on monkeys is reversible by later experience is unknown. In this study, we assessed the basal hair cortisol in rhesus monkeys after 1.5 and 3 y of normal social life following an early separation. These results showed that peer-reared monkeys had significantly lower basal hair cortisol levels than the mother-reared monkeys at both years examined. The plasma cortisol was assessed in the monkeys after 1.5 y of normal social life, and the results indicated that the peak in the peer-reared cortisol response to acute stressors was substantially delayed. In addition, after 3 y of normal social life, abnormal behavioral patterns were identified in the peer-reared monkeys. They showed decreases in locomotion and initiated sitting together, as well as increases in stereotypical behaviors compared with the mother-reared monkeys. These results demonstrate that the deleterious effects of MS on rhesus monkeys cannot be compensated by a later normal social life, suggesting that the effects of MS are long-lasting and that the maternal-separated rhesus monkeys are a good animal model to study early adversity and to investigate the development of psychiatric disorders induced by exposure to early adversity.
Adaptation of aerobic respiration to low O
2
environments
Authors: Han Huazhi , Hemp James , Pace Laura A. , Ouyang Hanlin , Ganesan Krithika , Roh Jung Hyeob , Daldal Fevzi , Blanke Steven R. , Gennis Robert B.
Published: August 2011

Aerobic respiration in bacteria, Archaea, and mitochondria is performed by oxygen reductase members of the heme-copper oxidoreductase superfamily. These enzymes are redox-driven proton pumps which conserve part of the free energy released from oxygen reduction to generate a proton motive force. The oxygen reductases can be divided into three main families based on evolutionary and structural analyses (A-, B- and C-families), with the B- and C-families evolving after the A-family. The A-family utilizes two proton input channels to transfer protons for pumping and chemistry, whereas the B- and C-families require only one. Generally, the B- and C-families also have higher apparent oxygen affinities than the A-family. Here we use whole cell proton pumping measurements to demonstrate differential proton pumping efficiencies between representatives of the A-, B-, and C-oxygen reductase families. The A-family has a coupling stoichiometry of 1 H
+
/e
-
, whereas the B- and C-families have coupling stoichiometries of 0.5 H
+
/e
-
. The differential proton pumping stoichiometries, along with differences in the structures of the proton-conducting channels, place critical constraints on models of the mechanism of proton pumping. Most significantly, it is proposed that the adaptation of aerobic respiration to low oxygen environments resulted in a concomitant reduction in energy conservation efficiency, with important physiological and ecological consequences.
Flow regime, temperature, and biotic interactions drive differential declines of trout species under climate change
Authors: Wenger Seth J. , Isaak Daniel J. , Luce Charles H. , Neville Helen M. , Fausch Kurt D. , Dunham Jason B. , Dauwalter Daniel C. , Young Michael K. , Elsner Marketa M. , Rieman Bruce E. , Hamlet Alan F. , Williams Jack E.
Published: August 2011

Broad-scale studies of climate change effects on freshwater species have focused mainly on temperature, ignoring critical drivers such as flow regime and biotic interactions. We use downscaled outputs from general circulation models coupled with a hydrologic model to forecast the effects of altered flows and increased temperatures on four interacting species of trout across the interior western United States (1.01 million km
2
), based on empirical statistical models built from fish surveys at 9,890 sites. Projections under the 2080s A1B emissions scenario forecast a mean 47% decline in total suitable habitat for all trout, a group of fishes of major socioeconomic and ecological significance. We project that native cutthroat trout
Oncorhynchus clarkii
, already excluded from much of its potential range by nonnative species, will lose a further 58% of habitat due to an increase in temperatures beyond the species’ physiological optima and continued negative biotic interactions. Habitat for nonnative brook trout
Salvelinus fontinalis
and brown trout
Salmo trutta
is predicted to decline by 77% and 48%, respectively, driven by increases in temperature and winter flood frequency caused by warmer, rainier winters. Habitat for rainbow trout,
Oncorhynchus mykiss
, is projected to decline the least (35%) because negative temperature effects are partly offset by flow regime shifts that benefit the species. These results illustrate how drivers other than temperature influence species response to climate change. Despite some uncertainty, large declines in trout habitat are likely, but our findings point to opportunities for strategic targeting of mitigation efforts to appropriate stressors and locations.
Bestatin-based chemical biology strategy reveals distinct roles for malaria M1- and M17-family aminopeptidases
Authors: Harbut Michael B. , Velmourougane Geetha , Dalal Seema , Reiss Gilana , Whisstock James C. , Onder Ozlem , Brisson Dustin , McGowan Sheena , Klemba Michael , Greenbaum Doron C.
Published: August 2011

Malaria causes worldwide morbidity and mortality, and while chemotherapy remains an excellent means of malaria control, drug-resistant parasites necessitate the discovery of new antimalarials. Peptidases are a promising class of drug targets and perform several important roles during the
Plasmodium falciparum
erythrocytic life cycle. Herein, we report a multidisciplinary effort combining activity-based protein profiling, biochemical, and peptidomic approaches to functionally analyze two genetically essential
P. falciparum
metallo-aminopeptidases (MAPs), PfA-M1 and Pf-LAP. Through the synthesis of a suite of activity-based probes (ABPs) based on the general MAP inhibitor scaffold, bestatin, we generated specific ABPs for these two enzymes. Specific inhibition of PfA-M1 caused swelling of the parasite digestive vacuole and prevented proteolysis of hemoglobin (Hb)-derived oligopeptides, likely starving the parasite resulting in death. In contrast, inhibition of Pf-LAP was lethal to parasites early in the life cycle, prior to the onset of Hb degradation suggesting that Pf-LAP has an essential role outside of Hb digestion.
Nucleic acid-binding polymers as anti-inflammatory agents
Authors: Lee Jaewoo , Sohn Jang Wook , Zhang Ying , Leong Kam W. , Pisetsky David , Sullenger Bruce A.
Published: August 2011

Dead and dying cells release nucleic acids. These extracellular RNAs and DNAs can be taken up by inflammatory cells and activate multiple nucleic acid-sensing toll-like receptors (TLR3, 7, 8, and 9). The inappropriate activation of these TLRs can engender a variety of inflammatory and autoimmune diseases. The redundancy of the TLR family encouraged us to seek materials that can neutralize the proinflammatory effects of any nucleic acid regardless of its sequence, structure or chemistry. Herein we demonstrate that certain nucleic acid-binding polymers can inhibit activation of all nucleic acid-sensing TLRs irrespective of whether they recognize ssRNA, dsRNA or hypomethylated DNA. Furthermore, systemic administration of such polymers can prevent fatal liver injury engendered by proinflammatory nucleic acids in an acute toxic shock model in mice. Therefore these polymers represent a novel class of anti-inflammatory agent that can act as molecular scavengers to neutralize the proinflammatory effects of various nucleic acids.
Mir-290–295
deficiency in mice results in partially penetrant embryonic lethality and germ cell defects
Authors: Medeiros Lea A. , Dennis Lucas M. , Gill Mark E. , Houbaviy Hristo , Markoulaki Styliani , Fu Dongdong , White Amy C. , Kirak Oktay , Sharp Phillip A. , Page David C. , Jaenisch Rudolf
Published: August 2011

Mir-290 through
mir-295
(
mir-290–295
) is a mammalian-specific microRNA (miRNA) cluster that, in mice, is expressed specifically in early embryos and embryonic germ cells. Here, we show that
mir-290–295
plays important roles in embryonic development as indicated by the partially penetrant lethality of mutant embryos. In addition, we show that in surviving
mir-290–295
-deficient embryos, female but not male fertility is compromised. This impairment in fertility arises from a defect in migrating primordial germ cells and occurs equally in male and female mutant animals. Male

mir-290–295
−/−

mice, due to the extended proliferative lifespan of their germ cells, are able to recover from this initial germ cell loss and are fertile. Female

mir-290–295
−/−

mice are unable to recover and are sterile, due to premature ovarian failure.
U
S
3 protein kinase of HSV-1 cycles between the cytoplasm and nucleus and interacts with programmed cell death protein 4 (PDCD4) to block apoptosis
Authors: Wang Xiaojia , Patenode Caroline , Roizman Bernard
Published: August 2011

The U
S
3 protein kinase of herpes simplex virus 1 plays a key role in blocking apoptosis induced by viral gene products or exogenous agents. The U
S
3 protein kinase is similar to protein kinase A with respect to substrate range and specificity. We report that in the yeast two-hybrid system a domain of U
S
3 essential for antiapoptotic activity reacted with programmed cell death protein 4 (PDCD4). We report that U
S
3 interacts with PDCD4, that PDCD4 is posttranslationally modified in infected cells both in a U
S
3-dependent and -independent fashion, and that depletion of PDCD4 by siRNA blocked apoptosis induced by a Δα4 mutant virus. In infected cells, PDCD4 accumulates in the nucleus, whereas U
S
3 accumulates in the cytoplasm. Studies designed to elucidate the convergence of these proteins led to the discovery that U
S
3 protein kinase cycles between the nucleus and cytoplasm and that U
S
3 retains PDCD4 in infected cell nuclei.
Actomyosin II contractility expels von Willebrand factor from Weibel–Palade bodies during exocytosis
Authors: Nightingale Thomas D. , White Ian J. , Doyle Emily L. , Turmaine Mark , Harrison-Lavoie Kimberly J. , Webb Kathleen F. , Cramer Louise P. , Cutler Daniel F.
Published: August 2011

The study of actin in regulated exocytosis has a long history with many different results in numerous systems. A major limitation on identifying precise mechanisms has been the paucity of experimental systems in which actin function has been directly assessed alongside granule content release at distinct steps of exocytosis of a single secretory organelle with sufficient spatiotemporal resolution. Using dual-color confocal microscopy and correlative electron microscopy in human endothelial cells, we visually distinguished two sequential steps of secretagogue-stimulated exocytosis: fusion of individual secretory granules (Weibel–Palade bodies [WPBs]) and subsequent expulsion of von Willebrand factor (VWF) content. Based on our observations, we conclude that for fusion, WPBs are released from cellular sites of actin anchorage. However, once fused, a dynamic ring of actin filaments and myosin II forms around the granule, and actomyosin II contractility squeezes VWF content out into the extracellular environment. This study therefore demonstrates how discrete actin cytoskeleton functions within a single cellular system explain actin filament–based prevention and promotion of specific exocytic steps during regulated secretion.
Loss of Roquin induces early death and immune deregulation but not autoimmunity
Authors: Bertossi Arianna , Aichinger Martin , Sansonetti Paola , Lech Maciej , Neff Frauke , Pal Martin , Wunderlich F. Thomas , Anders Hans-Joachim , Klein Ludger , Schmidt-Supprian Marc
Published: August 2011

The substitution of one amino acid in the Roquin protein by the sanroque mutation induces a dramatic autoimmune syndrome in mice. This is believed to occur through ectopic expression of inducible T cell co-stimulator (ICOS) and unrestrained differentiation of follicular T helper cells, which induce spontaneous germinal center reactions to self-antigens. In this study, we demonstrate that tissue-specific ablation of Roquin in T or B cells, in the entire hematopoietic system, or in epithelial cells of transplanted thymi did not cause autoimmunity. Loss of Roquin induced elevated expression of ICOS through T cell–intrinsic and –extrinsic mechanisms, which itself was not sufficient to break self-tolerance. Instead, ablation of Roquin in the hematopoietic system caused defined changes in immune homeostasis, including the expansion of macrophages, eosinophils, and T cell subsets, most dramatically CD8 effector–like T cells, through cell-autonomous and nonautonomous mechanisms. Germline Roquin deficiency led to perinatal lethality, which was partially rescued on the genetic background of an outbred strain. However, not even complete absence of Roquin resulted in overt self-reactivity, suggesting that the sanroque mutation induces autoimmunity through an as yet unknown mechanism.
An acetylcholine receptor lacking both γ and ε subunits mediates transmission in zebrafish slow muscle synapses
Authors: Mongeon Rebecca , Walogorsky Michael , Urban Jason , Mandel Gail , Ono Fumihito , Brehm Paul
Published: August 2011

Fast and slow skeletal muscle types in larval zebrafish can be distinguished by a fivefold difference in the time course of their synaptic decay. Single-channel recordings indicate that this difference is conferred through kinetically distinct nicotinic acetylcholine receptor (AChR) isoforms. The underlying basis for this distinction was explored by cloning zebrafish muscle AChR subunit cDNAs and expressing them in Xenopus laevis oocytes. Measurements of single-channel conductance and mean open burst duration assigned α2βδε to fast muscle synaptic current. Contrary to expectations, receptors composed of only αβδ subunits (presumed to be α2βδ2 receptors) recapitulated the kinetics and conductance of slow muscle single-channel currents. Additional evidence in support of γ/ε-less receptors as mediators of slow muscle synapses was reflected in the inward current rectification of heterologously expressed α2βδ2 receptors, a property normally associated with neuronal-type nicotinic receptors. Similar rectification was reflected in both single-channel and synaptic currents in slow muscle, distinguishing them from fast muscle. The final evidence for α2βδ2 receptors in slow muscle was provided by our ability to convert fast muscle synaptic currents to those of slow muscle by knocking down ε subunit expression in vivo. Thus, for the first time, muscle synaptic function can be ascribed to a receptor isoform that is composed of only three different subunits. The unique functional features offered by the α2βδ2 receptor likely play a central role in mediating the persistent contractions characteristic to this muscle type.
Statin effects on regulatory and proinflammatory factors in chronic idiopathic urticaria
Authors: Azor M H , dos Santos J C , Futata E A , de Brito C A , Maruta C W , Rivitti E A , da Silva Duarte A J , Sato M N
Published: August 2011

Immunological dysfunction has been described to occur in chronic idiopathic urticaria (CIU), most notably in association with an inflammatory process. Some pharmacological agents as statins – drugs used in hypercholesterolaemia – display a broad effect on the immune response and thus should be tested in vitro in CIU. Our main objectives were to evaluate the effects of statins on the innate and adaptive immune response in CIU. Simvastatin or lovastatin have markedly inhibited the peripheral blood mononuclear cells (PBMC) proliferative response induced by T and B cell mitogens, superantigen or recall antigen. Simvastatin arrested phytohaemaglutinin (PHA)-induced T cells at the G0/G1 phase, inhibiting T helper type 1 (Th1), Th2, interleukin (IL)-10 and IL-17A cytokine secretion in both patients and healthy control groups. Up-regulation of suppressor of cytokine signalling 3 (SOCS3) mRNA expression in PHA-stimulated PBMCs from CIU patients was not modified by simvastatin, in contrast to the enhancing effect in the control group. Statin exhibited a less efficient inhibition effect on cytokine production [IL-6 and macrophage inflammatory protein (MIP)-1α] induced by Toll-like receptor (TLR)-4, to which a statin preincubation step was required. Furthermore, statin did not affect the tumour necrosis factor (TNF)-α secretion by lipopolysaccharide (LPS)-stimulated PBMC or CD14+ cells in CIU patients. In addition, LPS-activated PBMC from CIU patients showed impaired indoleamine 2,3-dioxygenase (IDO) mRNA expression compared to healthy control, which remained at decreased levels with statin treatment. Statins exhibited a marked down-regulatory effect in T cell functions, but were not able to control TLR-4 activation in CIU patients. The unbalanced regulatory SOCS3 and IDO expressions in CIU may contribute to the pathogenesis of the disease.
Leading change: a three‐dimensional model of nurse leaders’ main tasks and roles during a change process
Authors: Salmela Susanne , Eriksson Katie , Fagerström Lisbeth
Published: August 2011

salmela s., eriksson k. & fagerström l. (2012) Leading change: a three‐dimensional model of nurse leaders’ main tasks and roles during a change process. Journal of Advanced Nursing 68(2), 423–433.

Aim.  This paper is a report of a qualitative study which explored how nurse leaders described and understood their main tasks and roles during a change process.

Background.  During a database search for literature, no actual research that highlighted the main tasks and roles of nurse leaders during a change process was found. Earlier research has indicated the need for different leadership styles and the importance of strategies and values.

Method.  In‐depth interviews with 17 nurse leaders took place in 2004. A phenomenological‐hermeneutical approach was used for data analysis.

Results.  The findings resulted in a model of leading change in health care that focuses on good patient care and consists of three dimensions: leading relationships, leading processes and leading a culture. In addition to leading relationships and processes, nurse leaders, as role models, greatly impact caring culture and its inherent ethical behaviour, especially about the responsibility for achieving good patient care. Nurse leaders are also instrumental in leading ward culture.

Conclusion.  Nurse leaders need guidance and knowledge of what is expected of them during a structural change process. They play different roles by directing, guiding, motivating, supporting and communicating without losing their cultural ethos of caring and use various leadership styles to bring about actual change, which, in turn, requires learning so that the thought patterns, values and attitudes of personnel can be changed.
Rapid diagnosis of the invasive species, Frankliniella occidentalis (Pergande): a species‐specific COI marker
Authors: Zhang G. F. , Meng X. Q. , Min L. , Qiao W. N. , Wan F. H.
Published: August 2011

The western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), is an invasive species and currently occurs in only a few areas in China. An easy, accurate and developmental‐stage independent method to identify F. occidentalis would be a valuable tool to facilitate pest management decision making and, more importantly, to provide an early warning so actions can be taken to prevent its introduction into non‐infested areas. Morphological identification of thrips adults and, to a lesser extent, of second‐stage larvae is the main method currently available to identify F. occidentalis. Molecular identification, however, can be easily carried out by a non‐thrips‐specialist with a little training. In this study, DNA sequence data [within the mitochondrial cytochrome oxidase I gene (COI)] and polymerase chain reaction (PCR) were utilized to develop a molecular diagnostic marker for F. occidentalis. A primer set and PCR cycling parameters were designed for the amplification of a single marker fragment (340 bp) of F. occidentalis COI mtDNA. Specificity tests performed on 28 thrips species, efficacy tests performed on five immature developmental stages as well as on male and female adults and tests on primer sensitivity all demonstrated the diagnostic utility of this marker. Furthermore, the primer set was tested on seventeen F. occidentalis populations from different countries and invaded areas in China and proved to be applicable for all geographic populations. It was used successfully to clarify the distribution of F. occidentalis in the Beijing metro area. These results suggested that this diagnostic PCR assay provides a quick, simple and reliable molecular technique for the identification of F. occidentalis.
Bayesian Meta-Analysis of Social Network Data via Conditional Uniform Graph Quantiles
Authors: Butts Carter T.
Published: August 2011

Many basic questions in the social network literature center on the distribution of aggregate structural properties within and across populations of networks. Such questions are of increasing relevance given the growing availability of network data suitable for meta-analytic studies, as well as the rise of study designs that involve the collection of data on multiple networks drawn from a larger population. Despite this, little work has been done on model-based inference for the properties of graph populations, or on methods for comparing such populations. Here, we attempt to rectify this gap by introducing a family of techniques that combines an existing approach to the identification of structural biases in network data (the use of conditional uniform graph quantiles) with strategies drawn from nonparametric Bayesian analysis. Conditional uniform graph quantiles are the quantiles of an observed structural property in the reference distribution produced by evaluating that property over all graphs with certain fixed characteristics (e.g., size or density). These quantiles have long been used to measure the extent to which a property of interest on a single network deviates from what would be expected given that network's other characteristics. The methods introduced here employ such quantile information to allow for principled inference regarding the distribution of structural biases within (and comparison across) populations of networks, given data sampled at the network level. The data requirements of these methods are minimal, thus making them well-suited to meta-analytic applications for which complete network data (as opposed to summary statistics) are often unavailable. The structural biases inferred using these methods can be expressed in terms of posterior predictives for familiar and easily communicated quantities, such as p-values. In addition to the methods themselves, we present algorithms for posterior simulation from this model class, illustrating their use with applications to the analysis of social structure within urban communes and radio communications among emergency personnel. We also discuss how this approach may applied to quantiles arising from other reference distributions, such as those obtained using general exponential-family random graph models.
Relation of reproductive performances and rectal palpation for luteum function of heifers 7 days after estrus
Authors: YOSHIDA Tatsuyuki , SEKI Makoto , WATANABE Norio , FURUTA Hiroki , YOSHIMURA Itaru , OSADA Masahiro , CHIBA Koji , OKADA Konosuke , KAWASUMI Koh , USHIJIMA Hitoshi
Published: August 2011

Diagnosis of corpus luteum (CL) function by rectal palpation (RP) has been widely used for recipient selection of embryo transfer (ET), a technology essential for genetic improvements in cattle. To examine the accuracy of RP diagnosis method, the relationship between RP‐based CL function and reproductive performance was compared in this study. In Experiment 1, CL of Holstein heifers on day 7 after estrus was classified into functional or hypoplastic by RP, and the results were compared with ultrasonographic (US) images and plasma progesterone (P4) levels. As a result, heifers with functional CL judged by RP had a mean maximum CL diameter of 20.1 ± 3.1 mm on US and a mean P4 concentration of 8.1 ± 2.3 ng/mL. These values were significantly greater than those of heifers with hypoplastic CL (12.4 ± 5.4 mm, 4.0 ± 2.8 ng/mL) (P < 0.001). In Experiment 2, the length of the estrus cycle was examined between functional CL and hypoplastic CL. The rate of heifers with a normal estrus cycle length with 18–25 days was significantly lower with hypoplastic CL than with functional CL (16/24 vs. 43/46, P < 0.01). In Experiment 3, 543 inseminated heifers were similarly classified by CL function by RP 7 days after estrus. The heifers with functional CL showed higher pregnancy rate compared with the heifers with hypoplastic CL (75.2 vs. 47.9%, P < 0.0001). Finally, the CL function of 66 heifers was examined by RP on day 7 post‐estrus, and ET was performed in 49 (74.2%) heifers with functional CL. As a result, 27 (55.1%) of them became pregnant. Taken together, these results reconfirm that RP on day 7 after estrus is useful for selection of heifers with functional CL.
Antimicrobial peptides important in innate immunity
Authors: Cederlund Andreas , Gudmundsson Gudmundur H. , Agerberth Birgitta
Published: August 2011

Antimicrobial peptides are present in all walks of life, from plants to animals, and they are considered to be endogenous antibiotics. In general, antimicrobial peptides are determinants of the composition of the microbiota and they function to fend off microbes and prevent infections. Antimicrobial peptides eliminate micro‐organisms through disruption of their cell membranes. Their importance in human immunity, and in health as well as disease, has only recently been appreciated. The present review provides an introduction to the field of antimicrobial peptides in general and discusses two of the major classes of mammalian antimicrobial peptides: the defensins and the cathelicidins. The review focuses on their structures, their main modes of action and their regulation.
Condominium and the City: The Rise of Property in Vancouver
Authors: Harris Douglas C.
Published: August 2011

Condominium is a form of land ownership that combines private ownership of an individual unit in a multi-unit building with an undivided share of the common property in the building and a right to participate in the collective governance of the private and common property. Introduced by statute across North America in the 1960s, condominium facilitated the vertical subdivision of land and enabled a massive increase in the density of private interests. This article describes condominium and considers the justifications that were offered for this rearrangement of property. It then chronicles the introduction of condominium to the city of Vancouver and maps its spread across the city from 1970 to 2010. In doing so, the article reveals that condominium, a legal innovation without peer in its capacity to increase the density of private ownership in land, has provided the legal architecture of ownership for the remaking of Vancouver.
Evaluation of Kidney Injury in Dogs with Pyometra Based on Proteinuria, Renal Histomorphology, and Urinary Biomarkers
Authors: Maddens B. , Heiene R. , Smets P. , Svensson M. , Aresu L. , van der Lugt J. , Daminet S. , Meyer E.
Published: August 2011

Background:Proteinuria is a feature of pyometra‐associated renal dysfunction, but its prevalence and clinical relevance are not well characterized.

Objectives:To define which subset of dogs with pyometra has clinically relevant kidney injury by quantification of proteinuria; light, immunofluorescence, and electron microscopic examination of kidney biopsy specimens; and measurement of urinary biomarkers.

Animals:Forty‐seven dogs with pyometra. Ten clinically healthy intact bitches of comparable age.

Methods:Prospective study. Routine clinicopathological variables including urinary protein to creatinine ratio (UPC) were analyzed. Validated assays were used to quantify urinary biomarkers for glomerular (urinary albumin, urinary immunoglobulin G, urinary C‐reactive protein, urinary thromboxane B2) and tubular function (urinary retinol‐binding protein, urinaryN‐acetyl‐β‐d‐glucosaminidase). Kidney biopsy specimens from 10 dogs with pyometra and dipstick urine protein concentrations of 2+ or 3+ were collected during ovariohysterectomy. Urinalysis was repeated within 3 weeks after surgery in 9 of the 10 dogs.

Results:UPC (median, range) was significantly higher in dogs with pyometra (0.48, 0.05–8.69) compared with healthy bitches (0.08, 0.02–0.16) (P< .01). Twenty‐two of 47 dogs with pyometra had UPC>0.5, 12 had UPC>1.0, and 7 had UPC>2.0. Glomerulosclerosis and tubulointerstitial nephritis were common kidney biopsy findings in proteinuric dogs with pyometra. Dogs with glomerulosclerosis (5/10), either global or focal and segmental, had UPC>1.0 at ovariohysterectomy and afterward. Dogs with structural glomerular and tubular changes mostly had urinary biomarker to creatinine ratios above the 75th percentile.

Conclusion:Dogs with pyometra and UPC>1.0 or high ratios of urinary biomarkers appear likely to have clinically relevant renal histologic lesions and require monitoring after ovariohysterectomy. Future studies should evaluate the role of pyometra‐associated pathogenic mechanisms in causing or exacerbating focal and segmental glomerulosclerosis in dogs.
Visual-Based Automation of Peg-in-Hole Microassembly Process
Authors: Chang R. J. , Lin C. Y. , Lin P. S.
Published: August 2011

An automatic visual-servo microassembly system is installed and tested. With a compliant polyurethane microgripper, a visual-servo system is implemented for micropeg alignment, micropeg transportation, and peg-in-hole assembly. The microassembly process is controlled by developing dynamic position-based servo through image calibration, regional-scanning with edge-fitting, and shadow-aided positioning algorithm. The main specifications of the system are gripping range of 60–90 μm, working space of 7 mm × 5.74 mm × 15 mm, and system bandwidth of 25 Hz. In performance test, cylindrical copper micropegs of diameter 80 μm and 88 μm are automatically aligned, gripped, transported, and assembled to a stainless rod with a mating hole of 100 μm.
Coherent Population Trapping Resonances in Cs Atomic Vapor Layers of Micrometric Thickness
Authors: Krasteva A. , Slavov D. , Cartaleva S.
Published: August 2011

We report on a novel behavior of the electromagnetically induced absorption (EIA) resonance observed on theD2line of Cs for atoms confined in cells with micrometric thickness. With the enhancement of light intensity, the EIA resonance amplitude suffers from fast reduction, and even at very low intensity (W < 1 mW/cm2), resonance sign reversal takes place and electromagnetically induced transparency (EIT) resonance is observed. Similar EIA resonance transformation to EIT one is not observed in conventional cm-size cells. A theoretical model is proposed to analyze the physical processes behind the EIA resonance sign reversal with light intensity. The model involves elastic interactions between Cs atoms as well as elastic interaction of atom micrometric-cell windows, both resulting in depolarization of excited state which can lead to the new observations. The effect of excited state depolarization is confirmed also by the fluorescence (absorption) spectra measurement in micrometric cells with different thicknesses.
Colorectal Cancers with Microsatellite Instability Display Unique miRNA Profiles
Authors: Balaguer Francesc , Moreira Leticia , Lozano Juan Jose , Link Alexander , Ramirez Georgina , Shen Yan , Cuatrecasas Miriam , Arnold Mildred , Meltzer Stephen J. , Syngal Sapna , Stoffel Elena , Jover Rodrigo , Llor Xavier , Castells Antoni , Boland C. Richard , Gironella Meritxell , Goel Ajay
Published: August 2011

Purpose: microRNAs (miRNA) are small noncoding transcripts that play an important role in carcinogenesis. miRNA expression profiles have been shown to discriminate between different types of cancers. The aim of this study was to analyze global miRNA signatures in various groups of colorectal cancers (CRC) based on the presence of microsatellite instability (MSI).

Experimental Design: We analyzed genome-wide miRNA expression profiles in 54 CRC tissues [22 with Lynch syndrome, 13 with sporadic MSI due to MLH1 methylation, 19 without MSI (or microsatellite stable, MSS)] and 20 normal colonic tissues by miRNA microarrays. Using an independent set of MSI-positive samples (13 with Lynch syndrome and 20 with sporadic MSI), we developed a miRNA-based predictor to differentiate both types of MSI by quantitative reverse transcriptase PCR.

Results: We found that the expression of a subset of nine miRNAs significantly discriminated between tumor and normal colonic mucosa tissues (overall error rate = 0.04). More importantly, Lynch syndrome tumors displayed a unique miRNA profile compared with sporadic MSI tumors; miR-622, miR-1238, and miR-192 were the most differentially expressed miRNAs between these two groups. We developed a miRNA-based predictor capable of differentiating between types of MSI in an independent sample set.

Conclusions: CRC tissues show distinct miRNA expression profiles compared with normal colonic mucosa. The discovery of unique miRNA expression profiles that can successfully discriminate between Lynch syndrome, sporadic MSI, and sporadic MSS colorectal cancers provides novel insights into the role of miRNAs in colorectal carcinogenesis, which may contribute to the diagnosis, prognosis, and treatment of this disease. Clin Cancer Res; 17(19); 6239–49. ©2011 AACR.
Dual EGFR/HER2 Inhibition Sensitizes Prostate Cancer Cells to Androgen Withdrawal by Suppressing ErbB3
Authors: Chen Liqun , Mooso Benjamin A. , Jathal Maitreyee K. , Madhav Anisha , Johnson Sherra D. , van Spyk Elyse , Mikhailova Margarita , Zierenberg-Ripoll Alexandra , Xue Lingru , Vinall Ruth L. , deVere White Ralph W. , Ghosh Paramita M.
Published: August 2011

Purpose: Patients with recurrent prostate cancer are commonly treated with androgen withdrawal therapy (AWT); however, almost all patients eventually progress to castration resistant prostate cancer (CRPC), indicating failure of AWT to eliminate androgen-sensitive prostate cancer. The overall goal of these studies is to determine whether dual inhibition of the receptor tyrosine kinases epidermal growth factor receptor (EGFR) and HER2 would prolong the effectiveness of this treatment in prostate cancer.

Experimental Design: We used androgen-dependent LNCaP cells and its CRPC sublines LNCaP-AI and C4-2. Additional data were collected in pRNS-1-1 cells stably expressing a mutant androgen receptor (AR-T877A), and in nude mice harboring CWR22 tumors. Studies utilized EGFR inhibitors erlotinib and AG1478, and HER2 inhibitors trastuzumab and AG879.

Results: Dual EGFR/HER2 inhibition induced apoptosis selectively in androgen-sensitive prostate cancer cells undergoing AWT, but not in the presence of androgens, or in CRPC cells. We show that AWT alone failed to induce significant apoptosis in androgen-dependent cells, due to AWT-induced increase in HER2 and ErbB3, which promoted survival by increasing Akt phosphorylation. AWT-induced ErbB3 stabilized the AR and stimulated PSA, while it was inactivated only by inhibition of both its dimerization partners EGFR and HER2 (prostate cancer cells do not express ErbB4); but not the inhibition of any one receptor alone, explaining the success of dual EGFR/HER2 inhibition in sensitizing androgen-dependent cells to AWT. The effectiveness of the inhibitors in suppressing growth correlated with its ability to prevent Akt phosphorylation.

Conclusion: These studies indicate that dual EGFR/HER2 inhibition, administered together with AWT, sensitize prostate cancer cells to apoptosis during AWT. Clin Cancer Res; 17(19); 6218–28. ©2011 AACR.
Vaccination with Different M2e Epitope Densities Confers Partial Protection against H5N1 Influenza A Virus Challenge in Chickens
Authors: Zhang Xintao , Liu Ming , Liu Chunguo , Du Jinling , Shi Weilin , Sun Encheng , Li Hongtao , Li Jianhui , Zhang Yun
Published: August 2011

Objective: Currently, research is focused on universal influenza vaccines based on various ectodomains of the influenza matrix protein 2 (M2e). Such vaccines are tested mostly using mouse-adapted influenza viruses and in mouse or ferret models. The aim of this study was to investigate in a chicken model the protective efficacy of vaccines based on avian-type M2e at different epitope densities. Methods: On the basis of the optimized avian-type M2e gene, recombinant plasmids that contained tandem copies of different M2e were constructed and expressed in Escherichia coli. The expression and immunogenicity of the proteins were confirmed by SDS-PAGE and Western blot, as well as immunofluorescence assay and enzyme-linked immunosorbent assay. Animals were immunized with fusion proteins emulsified with an appropriate adjuvant and then infected with highly pathogenic influenza virus of A/chicken/Guangdong/04 (H5N1). Antibody levels, survival rate and weight loss were investigated. Results: Multiple copies of M2e were highly expressed; higher epitope density engendered better protection but there was not a linear increase. Among the fusion proteins, the MBP-3·M2e fusion protein showed the best protective efficacy. Conclusions: This study has provided evidence that the immune response to avian-type M2e-based subunit vaccines was greater in chickens than that in mice. In addition, higher M2e epitope density can yield better protection, but not in a linear fashion.
Molecular Dating in the Evolution of Vertebrate Poxviruses
Authors: Babkin Igor V. , Babkina Irina N.
Published: August 2011

Objectives: The goal of this work was to study the evolutionary history of the vertebrate poxviruses using the Bayesian relaxed clock and a large set of highly conserved vitally important viral genes. Methods: Phylogenetic analysis was performed by the maximum likelihood method using the Paup program. The dating method of Bayes, realized in the Multidivtime, was made. Results: The rate of poxviral evolution is estimated as 0.5–7 × 10–6 nucleotide substitutions per site per year. We inferred that the modern viruses of the genus Avipoxvirus diverged from the ancestor nearly 249 ± 69 thousand years ago (Tya). The progenitor of the genus Orthopoxvirus separated approximately 166 ± 43 Tya. The separation of the forebear of the genus Leporipoxvirus took place about 137 ± 35 Tya. The next to diverge was the ancestor of the genus Yatapoxvirus. The progenitor of Capripoxvirus and Suipoxvirus diverged 111 ± 29 Tya. Conclusion: The evolutionary analysis based on the historical data and utilizing the Bayesian relaxed clock allowed us to determine the molecular evolution rates of the AT-rich genomes of the vertebrate poxviruses and assess the times of their emergences. Involvement of a large set of the conserved genes controlled by stabilizing selection allowed us to perform molecular dating of the vertebrate poxvirus history.
Necrosis of Ears after Use of Cocaine Probably Adulterated with Levamisole
Authors: de la Hera I. , Sanz V. , Cullen D. , Chico R. , Petiti G. , Villar M. , Burgués M. , Sanz J. , Castellanos M. , Zarco O. , Ortiz P.L. , Rodríguez-Peralto J.L. , Vanaclocha F.
Published: August 2011

Background/Aims: Levamisole is an anthelminthic drug with immunomodulatory properties that has been found to be an adulterant of cocaine in the last 2 years. It was present at least in 70% of tainted cocaine in the USA in 2009. Methods: We present the case of a 40-year-old patient with a history of weekend cocaine use who consulted for bilateral necrotic lesions in the ears that had appeared 3 days after the last use. Results: Levamisole causes a typical clinical picture characterized by bilateral necrosis of the ears, positive perinuclear antineutrophil cytoplasmic antibodies and laboratory findings of antiphospholipid syndrome, such as anticardiolipin antibodies and/or lupus anticoagulant. Conclusion: Dermatologists should be aware of this new entity, which is likely to be more and more frequent due to the increasing use of cocaine. Here we describe a clinical case that is likely to be secondary to levamisole-tainted cocaine and review the literature.
Comparative Effectiveness of Exercise Electrocardiography With or Without Myocardial Perfusion Single Photon Emission Computed Tomography in Women With Suspected Coronary Artery Disease
Authors: Shaw Leslee J. , Mieres Jennifer H. , Hendel Robert H. , Boden William E. , Gulati Martha , Veledar Emir , Hachamovitch Rory , Arrighi James A. , Bairey Merz C. Noel , Gibbons Raymond J. , Wenger Nanette K. , Heller Gary V. ,   for the WOMEN Trial Investigators
Published: August 2011

Background—

There is a paucity of randomized trials regarding diagnostic testing in women with suspected coronary artery disease (CAD). It remains unclear whether the addition of myocardial perfusion imaging (MPI) to the standard ECG exercise treadmill test (ETT) provides incremental information to improve clinical decision making in women with suspected CAD.

Methods and Results—

We randomized symptomatic women with suspected CAD, an interpretable ECG, and ≥5 metabolic equivalents on the Duke Activity Status Index to 1 of 2 diagnostic strategies: ETT or exercise MPI. The primary end point was 2-year incidence of major adverse cardiac events, defined as CAD death or hospitalization for an acute coronary syndrome or heart failure. A total of 824 women were randomized to ETT or exercise MPI. For women randomized to ETT, ECG results were normal in 64%, indeterminate in 16%, and abnormal in 20%. By comparison, the exercise MPI results were normal in 91%, mildly abnormal in 3%, and moderate to severely abnormal in 6%. At 2 years, there was no difference in major adverse cardiac events (98.0% for ETT and 97.7% for MPI;
P
=0.59). Compared with ETT, index testing costs were higher for exercise MPI (
P
<0.001), whereas downstream procedural costs were slightly lower (
P
=0.0008). Overall, the cumulative diagnostic cost savings was 48% for ETT compared with exercise MPI (
P
<0.001).

Conclusions—

In low-risk, exercising women, a diagnostic strategy that uses ETT versus exercise MPI yields similar 2-year posttest outcomes while providing significant diagnostic cost savings. The ETT with selective follow-up testing should be considered as the initial diagnostic strategy in symptomatic women with suspected CAD.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier: NCT00282711.
Uneasy Duets: Contemporary American Dances about Israel and the Mideast Crisis
Authors: Rossen Rebecca
Published: August 2011

Jewish choreographers have consistently created dances that embody the shifting role of Israel in American Jewish life. Countering the Zionism of mid-century dances about Israel, contemporary Jewish American choreographers such as Liz Lerman and Kristen Smiarowski actively question the ideology of unconditional support, deftly grapple with the Israeli-Palestinian conflict, and situate performance as an opportunity for activism, inquiry, and debate.
Three-point bending fatigue behavior of 3D angle-interlock woven composite
Authors: Jin Limin , Hu Hong , Sun Baozhong , Gu Bohong
Published: August 2011

This study reports the three-point bending fatigue behavior of three-dimensional angle-interlock glass/polyester woven composite (3DAWC). The S–N curve was obtained under the different bending stress levels. The bending stress vs. bending deflection curves were recorded to show the stiffness degradation and bending deformation of the 3DAWC during the fatigue test. The failure modes of the 3DAWC under the different fatigue loading conditions were photographed and compared with those in quasi-static bending tests. It was found that the integrated construction structure of the 3D angle-interlock woven fabric can resist the delamination of the 3DAWC under high-cycle fatigue loading. The cracks propagation and breakages of the warp yarns that run through the thickness direction of the 3DAWC dominate the fatigue failure. The resin cracks and resin-yarn interface debonding are the secondary factors for determining the fatigue behavior.
Experimental investigation of forced and wind assisted domestic solar hot water systems
Authors: Ramasamy K K , Srinivasan P S S
Published: August 2011

This paper investigates a proposal to replace the electrically operated pump of a forced circulation solar hot water system with a windmill-driven pump. A two-stage centrifugal pump driven by a vertical axis windmill with a Savonius type rotor is added to the fluid loop. Tests on the forced circulation system (FCS) mode, with two different pump speeds, driven by an electrically operated pump or in wind-assisted system (WAS) mode were carried out during January, April, July, and October 2009. Test results obtained on clear days are reported. A daily average thermal efficiency level of between 30 and 37 per cent was obtained in FCS mode and it was between 31 and 36 per cent in WAS mode. With higher wind velocities, higher collector flow rates and higher efficiencies are obtained. In general, the performance of a domestic hot water system operating in WAS mode is on a par with that obtained in FCS mode. The WAS mode is a viable alternative to FCS mode in remote areas where the supply of electricity is problematic.
From Dynasty to Songs of Praise: Television as cultural resource for gendered remembering
Authors: Keightley Emily
Published: August 2011

Despite detailed interrogations of the uses of media technologies and texts with overtly mnemonic functions in memory studies, there remains a limited engagement with the significance of television and everyday televisual texts in practices of remembering from specific social locations in the interests of performing and constructing particular social identities. Often, programming which refers to the past is considered from a textual rather than an audience perspective, and is viewed routinely through the analytical framework of history rather than memory. This article attempts to address this neglect by outlining the case for attending to television programmes beyond the conventionally historical as specifically gendered mnemonic resources. The article uses data drawn from in-depth interviews with women about their mnemonic practices to explore how they use television in everyday instances of remembering, and considers how these contribute to the articulation and construction of social identities.