bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Endothelial Cells and Progenitor Cell Subsets in Human Peripheral Blood
Authors: Estes Myka L. , Mund Julie A. , Ingram David A. , Case Jamie
Published: April 2010

An assay for circulating cell subsets in human peripheral blood by flow cytometry is used as a biomarker to determine cardiovascular disease risk and tumor responsiveness to chemotherapy since endothelial progenitor cells (EPCs) function in vasculogenesis and angiogenesis. Despite analytical advances in polychromatic flow cytometry (PFC), conventional approaches are routinely utilized to enumerate and isolate EPCs, which has led to varied results in clinical studies, potential cellular misidentification, and thus a lack of a plausible biological explanation for how purported EPCs function. Herein, a reproducible PFC protocol is provided to identify a rare circulating endothelial colony‐forming cell (ECFC) with proliferative potential, along with a population of circulating progenitor cells (CPCs) in which the ratio analysis distinguishes between healthy and disease populations. In sum, a reliable PFC protocol, which can be used to investigate the roles of human hematopoietic and endothelial elements in the growth and maintenance of the vasculature, is described. Curr. Protoc. Cytom. 52:9.33.1‐9.33.11. © 2010 by John Wiley & Sons, Inc.
Life Cycle Analysis of Unicellular Algae
Authors: Gerashchenko Bogdan I. , Takahashi Toshiyuki , Kosaka Toshikazu , Hosoya Hiroshi
Published: April 2010

Unicellular green alga is a very convenient object for flow cytometric characterization. Flow cytometry has been proposed as a quick and reliable tool for studying life cycle and growth of unicellular algae. Cell size of vegetating algae can be monitored in association with their DNA and endogenous chlorophyll content. Cells of interest (e.g., group of cells of a certain stage of the life cycle) in an asynchronously proliferating cell population can be sorted out for further microscopical or molecular biology studies. This methodological approach can be helpful for researchers who are interested in algal proliferation. Curr. Protoc. Cytom. 52:11.19.1‐11.19.6. © 2010 by John Wiley & Sons, Inc.
3D Deconvolution Microscopy
Authors: Biggs David S.C.
Published: April 2010

3D deconvolution microscopy is a combination of optical and computational techniques that are used to maximize the observed resolution and signal from a biological specimen. Mathematical models are used to predict the distribution of out‐of‐focus light caused by the inherent optical limitations of the instrument, which can then be compensated for using computer algorithms. This unit will review the theory of image formation and characteristics of the point spread function (PSF) based on the instrument modality and objective lens parameters. A variety of commonly used deblurring and deconvolution methods are described, and their applications to sample datasets are illustrated to show the performance of each algorithm. Steps for setting up the image acquisition to acquire data suitable for deconvolution are described, and the challenge of maximizing signal levels while minimizing light exposure addressed. Deconvolution examples from widefield epi‐fluorescence and laser scanning confocal are shown, and suitability for other modalities discussed. Curr. Protoc. Cytom. 52:12.19.1‐12.19.20. © 2010 by John Wiley & Sons, Inc.
Safety assessment on distillation columns: From shortcut methods and heuristics to dynamic simulation
Authors: Staak Daniel , Morillo Aristides , Schiffmann Patrick , Repke Jens‐Uwe , Wozny Günter
Published: April 2010

A new method for the design of safety devices for distillation columns based on dynamic simulation is presented. A simulation model for the description of the column behavior after an operational failure was developed and successfully validated. The model includes the description of weeping, entrainment, and pressure relief (one‐phase or two‐phase flow). Based on the simulation results, a more efficient design of safety measures is possible. © 2010 American Institute of Chemical Engineers AIChE J, 2011
The MECP2 duplication syndrome
Authors: Ramocki Melissa B. , Tavyev Y. Jane , Peters Sarika U.
Published: April 2010

In this review, we detail the history, molecular diagnosis, epidemiology, and clinical features of the MECP2 duplication syndrome, including considerations for the care of patients with this X‐linked neurodevelopmental disorder. MECP2 duplication syndrome is 100% penetrant in affected males and is associated with infantile hypotonia, severe to profound mental retardation, autism or autistic features, poor speech development, recurrent infections, epilepsy, progressive spasticity, and, in some cases, developmental regression. Most of the reported cases are inherited, however, de novo cases have been documented. While carrier females have been reported to be unaffected, more recent research demonstrates that despite normal intelligence, female carriers display a range of neuropsychiatric phenotypes that pre‐date the birth of an affected son. Given what we know of the syndrome to date, we propose that genetic testing is warranted in cases of males with infantile hypotonia and in cases of boys with mental retardation and autistic features with or without recurrent infections, progressive spasticity, epilepsy, or developmental regression. We discuss recommendations for clinical management and surveillance as well as the need for further clinical, genotype–phenotype, and molecular studies to assist the patients and their families who are affected by this syndrome. © 2010 Wiley‐Liss, Inc.
Synthesis and electrospun fiber mats of low Tg poly(propylene fumerate‐co‐propylene maleate)
Authors: Cicotte Kirsten N. , Hedberg‐Dirk Elizabeth L. , Dirk Shawn M.
Published: April 2010

Many publications have examined the biodegradable polymer poly(propylene fumate) (PPF) for use in tissue engineering applications. We have examined a similar crosslinkable polymer system, poly(propylene fumerate)‐co‐(propylene maleate) (PPFcPM), derived from maleic anhydride (MA) and 1,2‐propylene diol (PD). This copolymer system uses a less expensive monomer as well as leads to varied ratios of fumerate to maleate groups, allowing tuning of the crosslinked polymer properties such as degradation rate. Two different reaction conditions were used to synthesize the copolymer from MA and PD. In the first case (Method A), toluene was used as a solvent to azeotropically (85°C) remove water to drive the acid catalyzed esterification reaction. In the second case (Method B), the initial ring opening reaction was conducted, followed by addition of catalyst and removal of water to produce polymer of higher molecular weight. Both polymer systems had glass transition temperatures (Tg) below room temperature. The low Tg PPFcPM was dissolved in chloroform along with the photoinitiator phenylbis(2,4,6‐trimethylbenzoyl)‐phosphine oxide (BAPO) and electrospun. The polymer fibers were crosslinked soon after they formed to produce noncalendaring 3D porous scaffolds. Control experiments without the BAPO photoinitiator did not produce fiber mats. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Nanoclay reinforced rigid polyurethane foams
Authors: Kim S. H. , Lee M. C. , Kim H. D. , Park H. C. , Jeong H. M. , Yoon K. S. , Kim B. K.
Published: April 2010

Clay was intercalated and exfoliated by neutralized dimethylol butanoic acid (DMBA) and used to fabricate rigid polyurethane foam (RPUF)/clay nanocomposites. Cream time, gel time, and tack‐free time increased with the addition and increasing amount of clay whereas foam density and compression strength decreased. Cell size, closed cell content, volume change upon heating and cooling, and thermal conductivity of the foam decreased with the addition and increasing amount of clay with a minimum at 2 pphp (parts per 100 polyol by weight). The glass transition and decomposition temperatures increased with increasing clay content due to the restricted motion of chains and barrier property of the clay platelets. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Dangerous severe personality disorder: the controversy continues
Authors: Beck James C.
Published: April 2010

Following a high profile murder in 1996, the government in England moved to involuntarily contain individuals, almost all men, who were thought to be at risk of violence and to have a personality disorder. In 2008 the Dangerous Severe Personality Disorder program of assessment, commitment and treatment for this newly defined legal category of persons went into effect. The program was initially opposed by a majority of the forensic psychiatrists in England, but consistently supported by a minority. Copyright © 2010 John Wiley & Sons, Ltd.
Parent‐of‐origin and trans‐generational germline influences on behavioral development: The interacting roles of mothers, fathers, and grandparents
Authors: Curley J.P. , Mashoodh R.
Published: April 2010

Mothers and fathers do not contribute equally to the development of their offspring. In addition to the differential investment of mothers versus fathers in the rearing of offspring, there are also a number of germline factors that are transmitted unequally from one parent or the other that contribute significantly to offspring development. This article shall review four major sources of such parent‐of‐origin effects. Firstly, there is increasing evidence that genes inherited on the sex chromosomes including the nonpseudoautosomal part of the Y chromosome that is only inherited from fathers to sons, contribute to brain development and behavior independently of the organizing effects of sex hormones. Secondly, recent work has demonstrated that mitochondrial DNA that is primarily inherited only from mothers may play a much greater than anticipated role in neurobehavioral development. Thirdly, there exists a class of genes known as imprinted genes that are epigenetically silenced when passed on in a parent‐of‐origin specific manner and have been shown to regulate brain development and a variety of behaviors. Finally, there is converging evidence from several disciplines that environmental variations experienced by mothers and fathers may lead to plasticity in the development and behavior of offspring and that this phenotypic inheritance can be solely transmitted through the germline. Mechanistically, this may be achieved through altered programming within germ cells of the epigenetic status of particular genes such as retrotransposons and imprinted genes or potentially through altered expression of RNAs within gametes. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 312–330, 2010.
N‐cadherin is dispensable for pancreas development but required for β‐cell granule turnover
Authors: Johansson Jenny K. , Voss Ulrikke , Kesavan Gokul , Kostetskii Igor , Wierup Nils , Radice Glenn L. , Semb Henrik
Published: April 2010

The cadherin family of cell adhesion molecules mediates adhesive interactions that are required for the formation and maintenance of tissues. Previously, we demonstrated that N‐cadherin, which is required for numerous morphogenetic processes, is expressed in the pancreatic epithelium at E9.5, but later becomes restricted to endocrine aggregates in mice. To study the role of N‐cadherin during pancreas formation and function we generated a tissue‐specific knockout of N‐cadherin in the early pancreatic epithelium by inter‐crossing N‐cadherin‐floxed mice with Pdx1Cre mice. Analysis of pancreas‐specific ablation of N‐cadherin demonstrates that N‐cadherin is dispensable for pancreatic development, but required for β‐cell granule turnover. The number of insulin secretory granules is significantly reduced in N‐cadherin‐deficient β‐cells, and as a consequence insulin secretion is decreased. genesis 48:374–381, 2010. © 2010 Wiley‐Liss, Inc.
DNMT3a plays a role in switches between doxorubicin‐induced senescence and apoptosis of colorectal cancer cells
Authors: Zhang Yu , Gao Yanyan , Zhang Guoping , Huang Shuyan , Dong Zhixiong , Kong Chenfei , Su Dongmei , Du Juan , Zhu Shan , Liang Qian , Zhang Jianchao , Lu Jun , Huang Baiqu
Published: April 2010

The DNA‐damaging drug doxorubicin (Dox) induces cell senescence at concentrations significantly lower than those required for induction of apoptosis. At low Dox concentrations, tumor suppressor p53 is activated, which enhances the expression of p21Waf1/Cip1 (p21). At high concentrations, Dox activates p53 leading to apoptosis without enhancing p21 expression. The underlying mechanisms and factors that govern the differential effects of Dox in inducing senescence and apoptosis are unclear. Here, we report that the DNA methyltransferase (DNMT) DNMT3a was upregulated by Dox especially at concentrations that induced apoptosis in HCT116 colorectal cancer cells, and this process was regulated by p53. Meanwhile, p21 expression was significantly upregulated at senescence‐inducing concentrations and kept low on treatment with apoptosis‐inducing concentrations of Dox. The differential expression of DNMT3a and p21 in response to Dox suggests that DNMT3a may be a key factor in switches between Dox‐induced senescence and apoptosis. Moreover, when DNMT3a was silenced, treatment of HCT116 cells with apoptosis‐inducing concentration of Dox increased the percentage of cells undergoing senescence, accompanied by upregulation of p21. Contrarily, senescence‐inducing concentration of Dox promoted apoptosis rate, and p21 expression was repressed. Surprisingly, no changes in DNA methylation status at p21 promoter were detected at either ranges of Dox, although DNMT3a and HDAC1 were recruited to p21 promoter at apoptosis‐inducing Dox concentration, where they were present in the same complex. Overall, these data demonstrate that DNMT3a impacts the expression of p21 and plays a role in determining the Dox‐induced senescence and apoptosis in HCT116 cells.
Capecitabine plus oxaliplatin (XELOX) versus 5‐fluorouracil/leucovorin plus oxaliplatin (FOLFOX‐6) as first‐line treatment for metastatic colorectal cancer
Authors: Ducreux Michel , Bennouna Jaafar , Hebbar Mohamed , Ychou Marc , Lledo Gérard , Conroy Thierry , Adenis Antoine , Faroux Roger , Rebischung Christine , Bergougnoux Loic , Kockler Leila , Douillard Jean‐Yves
Published: April 2010

A regimen consisting of 5‐fluorouracil/leucovorin plus oxaliplatin (FOLFOX‐6) is widely used in France in the first‐line treatment of metastatic colorectal cancer (MCRC). The aim of our study was to demonstrate the non‐inferiority of capecitabine plus oxaliplatin (XELOX) versus FOLFOX‐6 for this indication. Patients were randomly assigned to receive XELOX or FOLFOX‐6 for 6 months. The primary endpoint was overall response rate (ORR) in the per‐protocol (PP) population; however, progression‐free and overall survival (OS), time to response and response duration were also assessed. A total of 306 patients were enrolled (XELOX n = 156; FOLFOX‐6 n = 150). ORR was 42 and 46% with XELOX and FOLFOX‐6, respectively, in the PP population. The difference between groups was 4.7%; the upper limit of the unilateral 95% confidence interval (14.4%) was below the non‐inferiority margin of 15%. In the intent‐to‐treat population, median progression‐free survival was 8.8 months with XELOX and 9.3 months with FOLFOX‐6, and median OS was 19.9 and 20.5 months, respectively. XELOX patients had significantly more grade 3/4 thrombocytopenia (12% vs. 5%) and diarrhoea (14% vs. 7%), but significantly less grade 3/4 neutropenia (5% vs. 47%), febrile neutropenia (0% vs. 6%) and neuropathy (11% vs. 26%) than FOLFOX‐6 patients. We conclude that XELOX is non‐inferior in terms of efficacy to FOLFOX‐6 in the first‐line treatment of MCRC, but has a different toxicity profile.
Hyperhomocysteinemia, methylenetetrahydrofolate reductase c.677C>T polymorphism and risk of cancer: Cross‐sectional and prospective studies and meta‐analyses of 75,000 cases and 93,000 controls
Authors: Zacho Jeppe , Yazdanyar Shiva , Bojesen Stig E. , Tybjærg‐Hansen Anne , Nordestgaard Børge G.
Published: April 2010

Global DNA hypomethylation associates with development of cancer. DNA hypomethylation also associates with hyperhomocysteinemia and MTHFR c.677C>T homozygosity, both of which may associate with increased risk of cancer. We tested the putative association of hyperhomocysteinemia with cancer and the association of the MTHFR c.677TC>T variant with hyperhomocysteinemia and with cancer. We performed a cross‐sectional study of 5,949 Danish general population adults, a prospective study of 9,235 Danish general population adults with up to 60 years of registry surveillance, and meta‐analyses of 231 studies including 74,671 cases and 93,344 controls. Cross‐sectionally, plasma homocysteine levels were 12.9 and 11.6 μmol/L in those with and without cancer (p < 0.0001). However, homocysteine levels increased with age and age‐adjusted odds ratio for any cancer in those with homocysteine levels >12.4 versus < 9.4 μmol/L did not differ from 1.0. In cancer‐free participants, plasma homocysteine levels were 14.7 and 11.7 μmol/L in MTHFR c.677C>T homozygtes and noncarriers (p < 0.0001). Prospectively, hazard ratios for any cancer and for cancer subtypes in MTHFR c.677C>T homozygotes versus noncarriers did not differ from 1.0. However, in meta‐analyses odds ratio for MTHFR c.677C>T homozygotes versus noncarriers were 1.07 (95% CI: 1.01–1.12) for any cancer, 1.77 (1.17–2.68) for esophagus cancer, 1.40 (1.19–1.66) for gastric cancer and 0.85 (0.77–0.94) for colorectal cancer. Increased plasma homocysteine levels are not associated with an increased age‐adjusted risk of any cancer. However, MTHFR c.677C>T homozygosity with lifelong hyperhomocysteinemia and hence hypomethylation associate with increased risk of esophagus and gastric cancer, and with decreased risk of colorectal cancer.
Berberine suppresses neuroinflammatory responses through AMP‐activated protein kinase activation in BV‐2 microglia
Authors: Lu Dah‐Yuu , Tang Chih‐Hsin , Chen Yi‐Hung , Wei I‐Hua
Published: April 2010

The AMPK cascade is a sensor of cellular energy change, which monitors the AMP/ATP ratio to regulate cellular metabolism by restoring ATP levels, but its regulation of neuroinflammation mechanism remains unclear. Berberine, one of the major constituents of Chinese herb Rhizoma coptidis, has been shown to improve several metabolic disorders, such as obesity and type II diabetes. However, the effect of berberine on neuroinflammatory responses in microglia are poorly understood. This study shows that berberine represses proinflammatory responses through AMP‐activated protein kinase (AMPK) activation in BV‐2 microglia. Our findings also demonstrate that berberine significantly down‐regulates LPS‐ or interferon (IFN)‐γ‐induced nitric oxide synthase (iNOS) and cyclo‐oxygenase‐2 (COX‐2) expression in BV‐2 microglia cells. Berberine also inhibited LPS‐ or IFN‐γ‐induced nitric oxide production. In addition, berberine effectively inhibited proinflammatory cytokines such as TNF‐α, IL‐1β, and IL‐6 expression. On the other hand, upon various inflammatory stimulus including LPS and IFN‐γ, berberine suppressed the phosphorylated of ERK but not p38 and JNK in BV‐2 microglia. AMPK activation is catalyzed by upstream kinases such as LKB1 and Ca2+/calmodulin‐dependent protein kinase kinase‐II (CaMKK II). Moreover, berberine induced LKB1 (Ser428), CaMKII (Thr286), and AMPK (Thr172) phosphorylation, but not AMPK (Ser485). Furthermore, the inhibitory effect of berberine on iNOS and COX‐2 expression was abolished by AMPK inhibition via Compound C, an AMPK inhibitor. Berberine‐suppressed ERK phosphorylation was also reversed by Compound C treatment. Our data demonstrate that berberine significantly induces AMPK signaling pathways activation, which is involved in anti‐neuroinflammation. J. Cell. Biochem. 110: 697–705, 2010. © 2010 Wiley‐Liss, Inc.
Smurf control in bone cells
Authors: Xing Lianping , Zhang Ming , Chen Di
Published: April 2010

The homologous to the E6‐assosiated protein carboxyl terminus (HECT) domain E3 ubiquitin ligase Smurf1 is the first E3 ligase to be implicated in regulating bone cell function. The involvement of Smurf1 in multiple signaling pathways and pathological conditions is presently an area of extensive scientific interest. This review highlights recent works exploring Smurf‐regulated biological processes in bone cells and highlights recent discoveries surrounding the regulatory mechanisms modulating its catalytic activity and substrate recognition capability. Moreover, we discuss the relevance of targeting the HECT E3s through the development of small‐molecule inhibitors as an anticancer therapeutic strategy. J. Cell. Biochem. 110: 554–563, 2010. © 2010 Wiley‐Liss, Inc.
Synthesis and characterization of dexamethasone‐conjugated linear polyethylenimine as a gene carrier
Authors: Kim Hyunjung , Bae Yun Mi , Kim Hyun Ah , Hyun Hyesun , Yu Gwang Sig , Choi Joon Sig , Lee Minhyung
Published: April 2010

Linear polyethylenimine (25 kDa, LPEI25k) has been shown to be an effective non‐viral gene carrier with higher transfection and lower toxicity than branched polyethylenimine (BPEI) of comparable molecular weight. In this study, dexamethasone was conjugated to LPEI25k to improve the efficiency of gene delivery. Dexamethasone is a synthetic glucocorticoid receptor ligand. Dexamethasone‐conjugated LPEI25k (LPEI–Dexa) was evaluated as a gene carrier in various cells. Gel retardation assays showed that LPEI–Dexa completely retarded plasmid DNA (pDNA) at a 0.75:1 weight ratio (LPEI/pDNA). LPEI–Dexa had the highest transfection efficiency at a 2:1 weight ratio (LPEI–Dexa/DNA). At this ratio, the size of the LPEI–Dexa/pDNA complex was approximately 125 nm and the zeta potential was 35 mV. LPEI–Dexa had higher transfection efficiency than LPEI and Lipofectamine 2000. In addition, the cytotoxicity of LPEI–Dexa was much lower than that of BPEI (25 kDa, BPEI25k). In conclusion, LPEI–Dexa has a high transfection efficiency and low toxicity and can therefore be used for non‐viral gene delivery. J. Cell. Biochem. 110: 743–751, 2010. © 2010 Wiley‐Liss, Inc.
Noradrenaline stimulates ATP release from DRG neurons by targeting β3 adrenoceptors as a factor of neuropathic pain
Authors: Kanno Takeshi , Yaguchi Takahiro , Nishizaki Tomoyuki
Published: April 2010

Noradrenaline (NA), released in association with sympathetic nerve sprouting into the dorsal root ganglion (DRG) after peripheral nerve injury, may enhance neuropathic pain. ATP serves as a pain mediator; however, NA‐regulated ATP mobilizations in the DRG is far from understanding. In the present study, we analyzed ATP mobilizations in acutely dissociated rat DRG neurons by recording single‐channel currents through P2X receptor channels as an ATP biosensor in an outside‐out patch‐clamp configuration and by monitoring real‐time enzymatic NADPH fluorescent imaging, and examined the role for β3 adrenoceptors in allodynia using an in vivo rat model. We show here that NA stimulates ATP release from DRG neurons as mediated via β3 adrenoceptors linked to Gs protein involving PKA activation, to cause allodynia. This represents a fresh regulatory pathway for neuropathic pain relevant to noradrenergic transmission in the DRG. J. Cell. Physiol. 224: 345–351, 2010. © 2010 Wiley‐Liss, Inc.
Dysregulated calcium homeostasis and oxidative stress in chronic myeloid leukemia (CML) cells
Authors: Ciarcia Roberto , d'Angelo Danila , Pacilio Carmen , Pagnini David , Galdiero Massimiliano , Fiorito Filomena , Damiano Sara , Mattioli Eliseo , Lucchetti Chiara , Florio Salvatore , Giordano Antonio
Published: April 2010

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder caused by the oncogenic activity of the Bcr‐Abl protein, a deregulated tyrosine kinase. Calcium may act directly on cellular enzymes and in conjunction with other cellular metabolites, such as cyclic nucleotides, to regulate cell functions. Alteration in the ionized calcium concentration in the cytosol has been implicated in the initiation of secretion, contraction, and cell proliferation as well as the production of reactive oxygen species (ROS) has been correlates with normal cell proliferation through activation of growth‐related signaling pathways. In this study we evaluated in peripheral blood leukocytes from CML patients the role of the balance between intracellular calcium and oxidative stress in CML disease in order to identify possible therapeutic targets in patients affected by this pathology. Our results demonstrated that peripheral blood mononuclear cells derived from CML patients displayed decreased intracellular calcium [Ca2+]i fluxes both after InsP3 as well as ATP and ionomycin (IONO) administration. CML cells showed lower levels of superoxide dismutase (SOD) activity and significantly higher malondialdehyde levels (MDA) than peripheral blood mononuclear cells derived from control patients. Finally we showed that resveratrol is able to down‐regulate InsP3 and ATP effects on intracellular calcium [Ca2+]i fluxes as well as the effects of ATP and IONO on oxidative stress in CML cells. J. Cell. Physiol. 224: 443–453, 2010. © 2010 Wiley‐Liss, Inc.
Role of proteoglycans and glycosaminoglycans in the pathogenesis of Alzheimer's disease and related disorders: Amyloidogenesis and therapeutic strategies—A review
Authors: Ariga Toshio , Miyatake Tadashi , Yu Robert K.
Published: April 2010

The extracellular accumulation of amyloid β proteins (Aβs) in neuritic plaques is one of the hallmarks of Alzheimer's disease (AD). The binding of Aβs to extracellular membranes (ECMs) is a critical step in developing AD. Aβs bind to many biomolecules, including lipids, proteins, and proteoglycans (PGs). PGs play several roles in amyloid formation, including promoting the aggregation of Aβs into insoluble amyloid fibrils, which contributes to the increased neurotoxicity of Aβs. Although Aβs readily self‐aggregate to form amyloid fibrils in vitro, their binding to PGs and heparin enhances amyloid aggregation and fibril formation. The sulfate moiety in glycosaminoglycans (GAGs), the carbohydrate portion of PGs, is necessary for the formation of amyloid fibrils; no fibrils are observed in the presence of hyaluronic acid (HA), a nonsulfated GAG. PGs and Aβs are known to colocalize in senile plaques (SPs) and neurofibrillary tangles (NFTs) in the AD brain. The binding site of PGs to Aβs has been identified in the 13–16‐amino‐acid region (His‐His‐Gln‐Lys) of Aβs and represents a unique target site for inhibition of amyloid fibril formation; His13 in particular is an important residue critical for interaction with GAGs. The sulfate moieties of GAGs play a critical role in the binding to Aβs and enhance Aβ fibril formation. Low‐molecular‐weight heparins (LMWHs) can reverse the process of amyloidosis to inhibit fibril formation by blocking the formation of β‐plated structures, suggesting a possible therapeutic approach using LMWHs to interfere with the interaction between PGs and Aβs and to arrest or prevent amyloidogenesis. © 2010 Wiley‐Liss, Inc.
The inhibitory neurotransmitter glycine modulates macrophage activity by activation of neutral amino acid transporters
Authors: Carmans Sofie , Hendriks Jerome J.A. , Thewissen Kristof , Van den Eynden Jimmy , Stinissen Piet , Rigo Jean‐Michel , Hellings Niels
Published: April 2010

Glycine, an important inhibitory neurotransmitter in the mammalian central nervous system (CNS), has been shown to modulate peripheral immune cell responses. In that respect, glycine levels are increased in several neuroinflammatory disorders, such as amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). In this study, we show that glycine modulates macrophage effector functions implicated in CNS inflammation and in other, related inflammatory conditions. We demonstrate that glycine does not affect the production of reactive oxygen species but stimulates myelin phagocytosis and the production of the proinflammatory mediators nitric oxide (NO) and tumor necrosis factor (TNF)‐α by rat macrophages. These effects of glycine are not mediated by the glycine receptor (GlyR) or by glycine transporters (GlyTs), as neither the GlyR antagonist strychnine nor the antagonist of GlyT1 (ALX5407) reverses the observed effects. In contrast, 2‐aminoisobutyric acid, a substrate of neutral amino acid transporters (NAATs), inhibits the glycine‐mediated enhancement of myelin phagocytosis as well as of NO and TNF‐α production. In conclusion, our findings demonstrate that glycine modulates macrophage function through activation of NAATs. Glycine may thereby influence immunological processes in inflammatory diseases involving macrophage activation and demyelination, including MS and related conditions associated with altered glycine levels. © 2010 Wiley‐Liss, Inc.
Preferential inhibition by antidiarrheic 2‐methoxy‐4‐methylphenol of Ca2+ influx across acquired N‐methyl‐D‐aspartate receptor channels composed of NR1/NR2B subunit assembly
Authors: Nakamichi Noritaka , Fukumori Ryo , Takarada Takeshi , Kambe Yuki , Yamamoto Tomomi , Matsushima Nobuyuki , Moriguchi Nobuaki , Yoneda Yukio
Published: April 2010

In our previous studies, particular phenolic ingredients, such as 2‐methoxy‐4‐methylphenol (2M4MP), of the antidiarrheic drug wood creosote significantly prevented cell death by both hydrogen peroxide and glutamate in cultured rat hippocampal neurons. In this study, we further evaluated the pharmacological properties of 2M4MP on Ca2+ influx across native and acquired N‐methyl‐D‐aspartate (NMDA) receptor (NMDAR) channels. The addition of 2M4MP significantly prevented the loss of cellular viability and the increase in intracellular free Ca2+ levels as determined by Fluo‐3 in cultured rat hippocampal neurons briefly exposed to NMDA. Brief exposure to NMDA also led to a marked increase in mitochondrial free Ca2+ levels determined by Rhod‐2, in addition to intracellular free Ca2+ levels, in HEK293 cells expressing either NR1/NR2A or NR1/NR2B subunit channels. The further addition of the general NMDAR channel blocker dizocilpine similarly inhibited the increase of intracellular Ca2+ levels by NMDA in both types of acquired NMDAR channels, whereas the NR2B subunit selective antagonist ifenprodil drastically inhibited the increase by NMDA in HEK293 cells expressing NR1/NR2B, but not NR1/NR2A, subunits. Similarly, 2M4MP significantly and selectively inhibited the NMDA‐induced influx of Ca2+ across acquired NR1/NR2B channels in a concentration‐dependent manner. Moreover, prior daily oral administration of 2M4MP significantly reduced the infarct volume in the ipsilateral cerebral hemisphere in rats with middle cerebral artery occlusion 1 day after reperfusion. These results suggest that 2M4MP may protect neurons from excitotoxicity through preferential inhibition of Ca2+ influx across NMDAR channels composed of NR1/NR2B subunits. © 2010 Wiley‐Liss, Inc.
Morphometric and anthropometric analysis of Killian's triangle
Authors: Anagiotos Andreas , Preuss Simon Florian , Koebke Juergen
Published: April 2010

Objectives/Hypothesis:

To determine the prevalence and the morphometric characteristics of Killian's triangle and to examine their relationship with the anthropometric features of the person.

Study Design:

Prospective.

Methods:

The hypopharyngeal wall was examined on 47 human cadavers. After a standardized method of dissection, the muscular structures of the hypopharyngeal wall were demonstrated and the existence or absence of Killian's triangle was determined. The triangle was examined in regard to its morphometric characteristics. In addition, anthropometric examinations of the whole body and of the head and neck regions on these cadavers were done, and the results were compared with the features of Killian's dehiscence.

Results:

A triangle of Killian was present on 60% (9/15) of the males and on 34% (11/32) of the females. The mean height for the males was 7 mm and for the females 4 mm, and the width was on average 16 mm and 12 mm, respectively. The dimensions of the triangle were correlated significantly with the dimensions of the body and with the length and the descensus of the larynx.

Conclusions:

The frequency and the dimensions of Killian's triangle appear to be greater in males than in females. Furthermore, the morphometric characteristics of the dehiscence show a correlation with the anthropometric features of the person. These findings can be an explanation for the higher incidence of Zenker's diverticulum with men and for the geographical differences of the diverticulum's frequency. Laryngoscope, 2010
Rheological study of solidified lubricant oils under very high pressure by observing microsphere deformation and viscosity prediction
Authors: Nakamura Yuichi , Takimoto Akira , Matsui Masahito
Published: April 2010

The rheological properties of solidified lubricant oils under pressure were evaluated by observing large plastic deformation of metal microspheres, occurring due to non‐hydrostatic pressurisation in the oils when using a diamond‐anvil cell pressure‐generating apparatus. Defining the solidification pressure as the onset pressure of plastic deformation of aluminum sphere obtained solidification pressures for traction oils were about 0.5 GPa, whereas those for mineral and synthetic oils ranged from 1.2 to 2 GPa. By substituting the solidification pressures and pressure–viscosity coefficients in the Barus equation, viscosities at the solidification pressure were obtained. The values were different for each oil and were within the order of 106–108 Pas. Based on several assumptions, shear stresses of the solidified oils could be estimated up to 5 GPa from the deformed Cu spheres. The shear stresses for a traction oil were almost equal to the mean shear stress obtained from a traction test between 1.0 and 1.7 GPa. Copyright © 2010 John Wiley & Sons, Ltd.
Experimental measuring procedure for the friction torque in rolling bearings
Authors: Cousseau Tiago , Graça Beatriz , Campos Armando , Seabra Jorge
Published: April 2010

The reduction of the power loss generated in mechanical transmissions and the use of low friction biodegradable lubricants has been attracting considerable attention in recent times. Therefore, it is necessary to develop methods to test and evaluate the performance of such lubricants and compare them with conventional ones.

In this sense, a Four‐Ball Machine was modified allowing the test of rolling bearings. A 51107 thrust ball bearing was used to test two different greases and the corresponding base oils. Friction torque and operating temperatures were continuously monitored to quantify the power loss and the heat evacuation for each lubricant tested. Copyright © 2010 John Wiley & Sons, Ltd.
Ex vivo assessment of mouse cervical remodeling through pregnancy via 23Na MRS
Authors: Xu Xiang , Akgul Yucel , Mahendroo Mala , Jerschow Alexej
Published: April 2010

Preterm birth occurs in 12.5% of births in the United States and can lead to risk of infant death or to lifelong serious health complications. A greater understanding by which the two main processes, uterine contraction and cervical remodeling are regulated is required to reduce rates of preterm birth. The cervix must undergo extensive remodeling through pregnancy in preparation for parturition, the process of labor and delivery of young. One key aspect of this dynamic process is a change in the composition and abundance of glycosaminoglycans (GAGs) and proteoglycans within the extracellular matrix, which influences the loss of tensile strength or stiffness of the cervix during labor. 23Na NMR spectroscopy has previously been validated as a method to quantify GAGs in tissues. In the current study, the Na+ concentration was measured at several time points through pregnancy in mouse cervices using 23Na NMR spectroscopy. The Na+ concentration increased progressively during pregnancy and peaked one day before birth followed by a rapid decline after birth. The same trend was seen in GAGs as measured by a biochemical assay using independent cervix samples over the course of pregnancy. We suggest that monitoring the Na+ concentration via 23Na NMR spectroscopy can serve as an informative physiological marker in evaluating the stages of cervical remodeling ex vivo and warrants further investigation to determine its utility as a diagnostic tool for the identification of women at risk for impending preterm birth. Copyright © 2010 John Wiley & Sons, Ltd.
Methods to apply probabilistic bias analysis to summary estimates of association
Authors: Lash Timothy L. , Schmidt Morten , Jensen Annette Østergaard , Engebjerg Malene Cramer
Published: April 2010

Purpose

Bias analysis methods are developed for application to 2 × 2 tables, which may be crude or stratified data. Methods for application to associations adjusted for multiple covariates, such as associations from regression modeling, are rarely seen. We have developed probabilistic methods to evaluate bias from disease misclassification or an unmeasured confounder that can be applied to adjusted estimates of association.

Methods

Rather than applying bias correction methods that rearrange data within 2 × 2 tables, we have applied them to bias factors directly. We illustrate the methods by application to two pharmacoepidemiology problems.

Results

In example one, the adjusted odds ratio associating glucocorticoid use with the rate of basal cell carcinoma was 1.15 (95%CI 1.07, 1.25). With bias analysis to account for differential disease misclassification, the median odds ratio was 1.32 and the 95% simulation limits were 1.16 and 1.56. In example two, the adjusted odds ratio associating concomitant use of clopidogrel and proton pump inhibitors with recurrent myocardial infarction was 1.21 (95%CI 0.90, 1.61). With bias analysis to account for confounding by smoking, which was unmeasured, the median odds ratio was 1.15 with 95% simulation interval 0.85 to 1.55.

Conclusion

Methods to apply probabilistic bias analysis to adjusted estimates of association can be implemented if a bias factor can be calculated directly from the bias model. This strategy requires that the bias is independent of confounding by measured variables, or requires that the dependence be incorporated into the bias model, as illustrated in an extension of the second example. Copyright © 2010 John Wiley & Sons, Ltd.
Strain‐hardening modulus of cross‐linked glassy poly(methyl methacrylate)
Authors: Wendlandt Michael , Tervoort Theo A. , Suter Ulrich W.
Published: April 2010

The strain hardening modulus, defined as the slope of the increasing stress with strain during large strain uniaxial plastic deformation, was extracted from a recently proposed constitutive model for the finite nonlinear viscoelastic deformation of polymer glasses, and compared to previously published experimental compressive true stress versus true strain data of glassy crosslinked poly(methyl methacrylate) (PMMA). The model, which treats strain hardening predominantly as a viscous process, with only a minor elastic contribution, agrees well with the experimentally observed dependence of the strain hardening modulus on strain rate and crosslink density in PMMA, and, in addition, predicts the well‐known decrease of the strain hardening modulus in polymer glasses with temperature. General scaling aspects of continuum modeling of strain hardening behavior in polymer materials are also presented. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1464–1472, 2010
Is psychological distress in men recently diagnosed with testicular cancer associated with their neuropsychological test performance?
Authors: Skaali Tone , Fosså Sophie D. , Andersson Stein , Langberg Carl W. , Lehne Gustav , Dahl Alv A.
Published: April 2010

Objective: To study the level of cancer‐related distress (CRD) and variables associated with CRD in recently diagnosed testicular cancer patients (TCPs), and to explore associations between distress levels and neuropsychological test performance at the same time‐point.

 Methods: As part of a prospective study of their psychological and cognitive functioning, 135 TCPs completed the Impact of Event Scale (IES) as a measure of CRD at a median of 37 days after diagnosis. They also completed the Hospital Anxiety and Depression Scale (HADS) and the Positive and Negative Affect Schedule (PANAS). Among 135 TCPs, 131 were interviewed and 129 were also tested with a neuropsychological battery. All investigations were done after orchidectomy but before any additional treatment. The associations between neuropsychological test‐scores and IES, HADS and PANAS were examined.

 Results: Twenty‐four percent (95%CI 17%–31%) of the TCPs reported clinically significant CRD (IES‐total score>26). No demographic or cancer‐related variables were associated with the CRD‐level. In univariate analyses, previous mental problems, sleeping problems, a higher level of neuroticism, daily smoking and hazardous alcohol‐use were significantly associated with the CRD‐level. In multivariate analysis neuroticism, smoking and alcohol‐use remained significantly associated with CRD. Four out of 18 neuropsychological test‐scores were significantly associated with at least one distress‐measure. Increasing distress‐levels were associated with decreasing test performance on some measures of attention, working memory and executive functions.

 Conclusions: In newly diagnosed TCPs, the scores on neuropsychological tests should be considered in relation to co‐existing mental distress. Future studies should consider adjustment for this on relevant tests. Copyright © 2010 John Wiley & Sons, Ltd.
Identifying barriers to treatment adherence and related attitudinal patterns in adolescents with cystic fibrosis
Authors: Dziuban Eric J. , Saab‐Abazeed Lisa , Chaudhry Sarah R. , Streetman Daniel S. , Nasr Samya Z.
Published: April 2010

Introduction

The treatment of cystic fibrosis (CF) is directed toward correction of organ dysfunction and relief of symptoms resulting from the disease. Lack of adherence to daily treatment regimens may have substantial short‐term and long‐term effects on patients with CF. In this study, we attempted to identify barriers to treatment adherence which could be predicted by objective measures and explore ways to improve adherence in adolescents with CF.

Methods

A questionnaire was given to patients 12.0–20.9 years of age, designed with focus on specific barriers to adhering to treatment plan and related attitudinal patterns. Observational and analytical results were collected.

Results

We obtained questionnaires and objective health data for 60 respondents. The most commonly identified barriers to adherence were forgetting or losing medications (32/60) and being too busy (23/60). Attitudinal patterns that played a significant role for nonadherence included unintentional forgetting (40/60), feeling that following CF treatments resulted in less freedom in their lives (30/60), and believing it is acceptable to miss a treatment every few days (18/60) or to miss treatments when busy (18/60).

Discussion

There were a few statistically significant differences of adherence patterns between demographic subgroups in our study. Males were more likely to agree that it is acceptable to miss doses if they are made up with extra doses later (24% vs. 3%, P = 0.04). Patients who perceived themselves to be less healthy agreed more to statements of limited freedom, nonsympathetic medical providers, and difficulty adhering during times of decreased symptoms. This highlights an unexpected risk: as CF progresses and patients perceive themselves to be less healthy, they may become less likely to be adherent during the periods they are feeling the best, while at the same time becoming less likely to perceive empathy from their physicians.

Conclusions

Survey results describe a variety of beliefs and attitudinal patterns which contribute to nonadherence in CF treatment, especially relating to time management. While patients largely understood the importance of treatments to their health, predictors of risky behaviors could lead to targeted interventions by CF centers to address these challenges and improve adherence. Pediatr Pulmonol. 2010; 45:450–458. © 2010 Wiley‐Liss, Inc.
A Bayesian model for the joint optimization of quality and maintenance decisions
Authors: Nenes George , Panagiotidou Sofia
Published: April 2010

We develop a model for the economic design of a Bayesian control chart for monitoring a process mean. The process may randomly suffer failures that result in a non‐operating state, and thus call for an immediate corrective maintenance action, as well as assignable causes that shift the process mean to an undesirable level. Quality shifts, apart from poorer quality outcome and higher operational cost, also result in higher failure rate. Consequently, their removal, besides improving the outcome quality and reducing the quality‐related cost, is also a preventive maintenance action since it reduces the probability of a failure. The proposed Bayesian model allows the determination of the design parameters that minimize the total expected quality and maintenance cost per time unit. The effectiveness of the proposed model is evaluated through the comparison of its expected cost against the optimum expected cost of the simpler variable‐parameter Shewhart chart. Copyright © 2010 John Wiley & Sons, Ltd.
Paradoxes of design: energy and water consumption and the aestheticization of Norwegian bathrooms 1990–2008
Authors: Berker Thomas , Gansmo Helen Jøsok
Published: April 2010

In this article we explore the widely held assumption that aestheticized consumption is bound to escalate. In our study of 20 years of representations of bathrooms in Norway's most popular interior design magazineBonytt, we found support for the hypothesis that since the early 1990s new uses of bathrooms as sites for the construction and expression of identity and social aspirations have become more salient. We also have reason to believe that these new uses may be related to increased energy and water consumption. However, we also encountered aspects that indicate a more contingent and paradoxical relation. First,Bonyttcalls explicitly forreflexiveconsumerism, enabling readers to deliberate the degree of aestheticization of their bathrooms. Second, while mostly showing large bathrooms, ‘aesthetic fixes’ are proposed byBonytt, which let small bathrooms appear larger – without increased energy consumption for space heating. Third, aesthetics is used to propagate new, energy saving technologies (e.g. LEDs). And fourth, water and energy wasting practices shown in newerBonyttissues (e.g. large shower heads) have largely replaced wasteful practices present in older issues (e.g. whirlpools). Thus, at least in these cases the shifts in fashions promoted byBonyttmay only be surface phenomena, which leave more fundamental trends untouched. These four observations are examples of how a productive relation between design and sustainability can be achieved. Copyright © 2010 John Wiley & Sons, Ltd and ERP Environment.
DNA damage and effects on glutathione‐S‐transferase activity induced by atrazine exposure in zebrafish (Danio rerio)
Authors: Zhu Lusheng , Dong Xiaoli , Xie Hui , Wang Jun , Wang Jinhua , Su Jun , Yu Changwei
Published: April 2010

This study was undertaken to investigate the protective effect of atrazine (2‐chloro‐4‐(ethylamino)‐6‐(isopropylamino)‐S‐triazine) on the activity of glutathione‐S‐transferase (GST) and DNA damage in males and females of adult zebrafish (Danio rerio). Zebrafish were exposed to control and three treatments (0.01, 0.1, and 1 mg/L) of atrazine for 5, 10, 15, 20, and 25 days. The results indicated that, for males, the GST activity at lower atrazine concentrations (0.01 and 0.1 mg/L) was markedly higher than that of the controls throughout the duration of the experiment while there was a significant inhibition of the GST activity at 1 mg/L atrazine at days 5 and 20. For females, a significant increase was detected at 0.1 mg/L on the days 5 and 15 and at 0.01 mg/L on day 20. The DNA damage in zebrafish was evaluated using the comet assay; the olive tail moments obtained for hepatopancreas were enhanced after treatment with different concentrations of atrazine on days 5, 10, 15, 20, and 25. The DNA damage increased with increasing atrazine concentrations, indicating that genotoxicity of atrazine and significant differences was found compared to the controls. In conclusion, these findings provide further evidence of the effects of atrazine on aquatic ecosystems. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2010.