bluuebunny/crossref_metadata_2025 huggingface dataset:
CCN2 is required for bleomycin‐induced skin fibrosis in mice
Authors: Liu Shangxi , Shi‐wen Xu , Abraham David J. , Leask Andrew
Published: October 2010

Objective

No therapy for fibrotic disease is available. The proadhesive matricellular protein connective tissue growth factor CCN2 is a marker of fibrotic cells; however, the specific role of CCN2 in connective tissue biology in general and in fibrogenesis in particular is unclear. The aim of this study was to assess whether adult mice bearing a smooth muscle cell/fibroblast–specific deletion of CCN2 are resistant to bleomycin‐induced skin scleroderma.

Methods

Cutaneous fibrosis was induced in mice by subcutaneous injection of bleomycin. Untreated control groups were injected with phosphate buffered saline. Mice bearing a fibroblast/smooth muscle cell–specific deletion of CCN2 were investigated for changes in dermal thickness, collagen content, and the number of α‐smooth muscle actin (α‐SMA)–positive cells. Dermal fibroblasts were isolated to assess whether the induction of collagen and α‐SMA messenger RNA in response to transforming growth factor β (TGFβ) was impaired.

Results

The loss of CCN2 resulted in resistance to bleomycin‐induced skin fibrosis. In response to bleomycin, wild‐type mice possessed, but CCN2‐deficient mice lacked, abundant α‐SMA–expressing myofibroblasts within fibrotic lesions. Fibroblast responses to TGFβ, a potent inducer of myofibroblast differentiation, were not affected. Collectively, these results indicate that CCN2 is essential for bleomycin‐induced skin fibrosis, likely due to a defect in myofibroblast recruitment.

Conclusion

These data indicate that therapeutic strategies that involve blocking CCN2 in vivo may be of benefit in combating fibrotic skin disease.
Combined pulmonary fibrosis and emphysema syndrome in connective tissue disease
Authors: Cottin Vincent , Nunes Hilario , Mouthon Luc , Gamondes Delphine , Lazor Romain , Hachulla Eric , Revel Didier , Valeyre Dominique , Cordier Jean‐François ,   Groupe d'Etudes et de Recherche sur les Maladies “Orphelines” Pulmonaires
Published: October 2010

Objective

Connective tissue diseases (CTDs) are associated with several interstitial lung diseases. The aim of this study was to describe the recently individualized syndrome of combined pulmonary fibrosis and emphysema (CPFE) in a population of patients with CTD.

Methods

In this multicenter study, we retrospectively investigated data from patients with CTD who also have CPFE. The demographic characteristics of the patients, the results of pulmonary function testing, high‐resolution computed tomography, lung biopsy, and treatment, and the outcomes of the patients were analyzed.

Results

Data from 34 patients with CTD who were followed up for a mean ± SD duration of 8.3 ± 7.0 years were analyzed. Eighteen of the patients had rheumatoid arthritis (RA), 10 had systemic sclerosis (SSc), 4 had mixed or overlap CTD, and 2 had other CTDs. The mean ± SD age of the patients was 57 ± 11 years, 23 were men, and 30 were current or former smokers. High‐resolution computed tomography revealed emphysema of the upper lung zones and pulmonary fibrosis of the lower zones in all patients, and all patients exhibited dyspnea during exercise. Moderately impaired pulmonary function test results and markedly reduced carbon monoxide transfer capacity were observed. Five patients with SSc exhibited pulmonary hypertension. Four patients died during followup. Patients with CTD and CPFE were significantly younger than an historical control group of patients with idiopathic CPFE and more frequently were female. In addition, patients with CTD and CPFE had higher lung volumes, lower diffusion capacity, higher pulmonary pressures, and more frequently were male than those with CTD and lung fibrosis without emphysema.

Conclusion

CPFE warrants inclusion as a novel, distinct pulmonary manifestation within the spectrum of CTD‐associated lung diseases in smokers or former smokers, especially in patients with RA or SSc.
Alternating and Diblock Donor–Acceptor Conjugated Polymers Based on Diindeno[1,2‐b:2′,1′‐d]thiophene Structure: Synthesis, Characterization, and Photovoltaic Applications
Authors: Chen Chiu‐Hsiang , Cheng Yen‐Ju , Dubosc Martin , Hsieh Chao‐Hsiang , Chu Cheng‐Che , Hsu Chain‐Shu
Published: October 2010

Pentacyclic diindeno[1,2‐b:2′,1′‐d]thiophene (DIDT) unit is a rigid and coplanar conjugated molecule. To the best of our knowledge, this attractive molecule has never been incorporated into a polymer and thus its application in polymer solar cells has never been explored. For the first time, we report the detailed synthesis of the tetra‐alkylated DIDT molecule leading to its dibromo‐ and diboronic ester derivatives, which are the key monomers for preparation of DIDT‐based polymers. Two donor–acceptor alternating polymers, poly(diindenothiophene‐alt‐benzothiadiazole) PDIDTBT and poly(diindenothiophene‐alt‐dithienylbenzothiadiazole) PDIDTDTBT, were synthesized by using Suzuki polymerization. Copolymer PTDIDTTBT was also prepared by using Stille polymerization. Although PTDIDTTBT is prepared through a manner of random polymerization, we found that the different reactivities of the dibromo‐monomers lead to the resulting polymer having a block copolymer arrangement. With the higher structural regularity, PTDIDTTBT, symbolized as (thiophene‐alt‐DIDT)0.5‐block‐(thiophene‐alt‐BT)0.5, shows the higher degree of crystallization, stronger π–π stacking, and broader absorption spectrum in the solid state, as compared to its alternating PDIDTDTBT analogue. Bulk heterojunction photovoltaic cells based on ITO/PEDOT:PSS/polymer:PC71BM/Ca/Al configuration were fabricated and characterized. PDIDTDTBT/PC71BM and PTDIDTTBT/PC71BM systems exhibited promising power‐conversion efficiencies (PCEs) of 1.65 % and 2.00 %, respectively. Owing to the complementary absorption spectra, as well as the compatible structures of PDIDTDTBT and PTDIDTTBT, the PCE of the device based on the ternary blend PDIDTDTBT/PTDIDTTBT/PC71BM was further improved to 2.40 %.
Double‐Pillaring Strategy for Silacyclophanes: Synthesis and Structures of Disilanyl Double‐Pillared Bisanthracenes
Authors: Nakanishi Waka , Hitosugi Shunpei , Shimada Yusuke , Isobe Hiroyuki
Published: October 2010

A new series of silacyclophanes with two disilanyl pillars has been synthesized using a straightforward method. A silylation reaction of 1,8‐dilithioanthracenes allowed the connection of two anthracene rings with two SiSi bonds to afford disilanyl double‐pillared bisanthracenes (SiDPBAs). The major product had an anti geometry of the anthracene rings, and a unique steplike structure favorable for σ–π conjugations was revealed by X‐ray crystallographic analysis. Upon introducing a substituent at the 10‐position of anthracene, we obtained a U‐shaped isomer with syn geometry that yielded an excimer upon excitation and can decompose without steric protection.
Total Synthesis of Dictyodendrins A–E
Authors: Tokuyama Hidetoshi , Okano Kentaro , Fujiwara Hideto , Noji Toshiharu , Fukuyama Tohru
Published: October 2010

A highly efficient total synthesis of dictyodendrins A–E was accomplished. The synthesis features a novel benzyne‐mediated one‐pot indoline formation/cross‐coupling sequence for the construction of a highly substituted key indoline intermediate. Peripheral substituents were introduced onto this intermediate in a modular fashion to complete the total synthesis of dictyodendrins A–E.
Altered health outcomes in adult offspring of Sprague Dawley and Wistar rats undernourished during early or late pregnancy
Authors: Ellis‐Hutchings Robert G. , Zucker Robert M. , Grey Brian E. , Norwood Joel , Richards Judy H. , Lau Christopher , Rogers John M.
Published: October 2010

BACKGROUND: Birth weight in humans has been inversely associated with adult disease risk. Results of animal studies have varied depending on species, strain, and treatment. METHODS: We compared birth weight and adult health in offspring following 50% maternal undernutrition on gestation days (GD) 1–15 (UN1–15) or GD 10–21 (UN10–21) in Sprague Dawley and Wistar rats. Offspring from food‐deprived dams were weighed and cross‐fostered to control dams. Litters were weighed during lactation and initiating at weaning males were fed either control or a high‐fat diet. Young and mature adult offspring were evaluated for obesity, blood pressure (BP), insulin response to oral glucose, and serum lipids. Nephron endowment, renal glucocorticoid receptor, and renin–aldosterone–angiotensin system components were measured. RESULTS: The UN10–21 groups had birth weights lower than controls and transient catch up growth by weaning. Neither strain demonstrated obesity or dyslipidemia following prenatal undernutrition, but long‐term body weight deficits occurred in the UN groups of both strains. High‐fat diet fed offspring gained more weight than control offspring without an effect of prenatal nutrition. Sprague Dawley were slightly more susceptible than Wistar rats to altered insulin response and increased BP following gestational undernutrition. Nephron endowment in Sprague Dawley but not Wistar offspring was lower in the UN10–21 groups. Glucocorticoid and renin–aldosterone–angiotensin system pathways were not altered. CONCLUSIONS: The most consistent effect of maternal undernutrition was elevated BP in offspring. Long‐term health effects occurred with undernutrition during either window, but the UN10–21 period resulted in lower birth weight and more severe adult health effects. Birth Defects Res (Part B) 89:396–407, 2010. © 2010 Wiley‐Liss, Inc.
Toward the First Nonpeptidic Molecular Tong Inhibitor of Wild‐Type and Mutated HIV‐1 Protease Dimerization
Authors: Vidu Anamaria , Dufau Laure , Bannwarth Ludovic , Soulier Jean‐Louis , Sicsic Sames , Piarulli Umberto , Reboud‐Ravaux Michèle , Ongeri Sandrine
Published: October 2010

Herein we describe the synthesis and HIV‐1 protease (PR) inhibitory activity of 16 new peptidomimetic molecular tongs with a naphthalene scaffold. Their peptidic character was progressively decreased. Two of these molecules exhibited the best dimerization inhibition activity toward HIV‐1 wild‐type and multimutated ANAM‐11 proteases obtained to date for this class of molecules (∼40 nM for wild‐type PR and 100 nM for ANAM‐11 PR). Although the peptidic character of one molecular tong was completely suppressed, the mechanism of inhibition and inhibitory potency toward both proteases were maintained.
Short duration of sleep increases risk of colorectal adenoma
Authors: Thompson Cheryl L. , Larkin Emma K. , Patel Sanjay , Berger Nathan A. , Redline Susan , Li Li
Published: October 2010

BACKGROUND:

Short duration and poor quality of sleep have been associated with increased risks of obesity, cardiovascular disease, diabetes mellitus, and total mortality. However, few studies have investigated their associations with risk of colorectal neoplasia.

METHODS:

In a screening colonoscopy‐based case‐control study, the Pittsburg Sleep Quality Index (PSQI) was administered to 1240 study participants before colonoscopy.

RESULTS:

Three hundred thirty‐eight (27.3%) of the participants were diagnosed with incident colorectal adenomas. Although there was no appreciable difference in the overall PSQI score between cases and adenoma‐free controls (5.32 vs 5.11; P = .37), the authors found a statistically significant association of colorectal adenoma with the PSQI component 3, which corresponds to sleep duration (P = .02). Cases were more likely to average less than 6 hours of sleep per night (28.9% vs 22.1% in controls, P = .01). In multivariate regression analysis adjusted for age, gender, race, smoking, family history of colorectal cancer, and waist‐to‐hip ratio, individuals averaging less than 6 hours per night had an almost 50% increase in risk of colorectal adenomas (OR = 1.47; CI = 1.05‐2.06, P for trend = .02) as compared with individuals sleeping at least 7 hours per night. Cases were also more likely to report being diagnosed with sleep apnea (9.8% vs 6.5%, P = .05) and more likely to have worked alternate shifts (54.0% vs 46.1%, P = .01), although these differences were not significant in multivariate models.

CONCLUSIONS:

Shorter duration of sleep significantly increases risk of colorectal adenomas. The authors' results suggest sleep duration as a novel risk factor for colorectal neoplasia. Cancer 2011. © 2010 American Cancer Society.
Water Splitting over New Niobate Photocatalysts with Tungsten‐Bronze‐Type Structure and Effect of Transition Metal‐Doping
Authors: Miseki Yugo , Kudo Akihiko
Published: October 2010

Photophysical properties and photocatalytic activities for water splitting over KM2Nb5O15 (M=Sr and Ba) and K2LnNb5O15 (Ln=La, Pr, Nd, and Sm) with tungsten bronze‐type structure were investigated. Single phases of KM2Nb5O15 and K2LnNb5O15 were successfully prepared by solid‐state reaction (SSR) method and polymerizable complex (PC) method. The band gaps of these niobates were estimated to be 3.1–3.5 eV. These metal oxides loaded with an activated NiOx cocatalyst showed photocatalytic activities for water splitting into H2 and O2 under UV irradiation. When K2LaNb5O15 was doped by Rh ions, a new visible‐light absorption band was observed around 400–500 nm in addition to the band gap absorption band of the K2LaNb5O15 host. K2LaNb5O15:Rh showed photocatalytic activities for H2 or O2 evolution from an aqueous solution containing a sacrificial reagent under visible‐light irradiation.
Prevention of type 1 diabetes: today and tomorrow
Authors: Cernea Simona , Dobreanu Minodora , Raz Itamar
Published: October 2010

The aim of therapeutic interventions for type 1 diabetes is to suppress pathogenic autoreactivity and to preserve/restore beta‐cell mass and function to physiologically sufficient levels to maintain good metabolic control. During the natural history of type 1 diabetes, several strategies have been applied at various stages in the form of primary, secondary or tertiary prevention approaches. Clinical trials using antigen‐specific (e.g. DiaPep277, human glutamic acid decarboxylase 65 (GAD65)) or non‐specific immune therapies (e.g. anti‐CD3 monoclonal antibodies) have shown some benefit in the modulation of the autoimmune process and prevention of the insulin secretion loss in the short term after diagnosis of diabetes. A single long‐term effective therapy has not been identified yet, and it is likely that in most cases a rationally designed combinatorial approach using immunotherapeutic methods coupled with islet regeneration or replacement will prove to be most effective. Copyright © 2010 John Wiley & Sons, Ltd.
Can atmospheric circulation be linked to flooding in Europe?
Authors: Prudhomme Christel , Genevier Marie
Published: October 2010

This paper evaluates whether circulation type catalogues (CTCs) can inform on the occurrence of floods in Europe, and if the same few circulation types (CTs) are systematically associated with floods at the European scale. A measure of the spatial coherence of CT was introduced to compare the relative performance of CTCs in discriminating flood events, based on a local indicator measuring if a CT occurs more frequently than usual prior/during a flood. Antecedent conditions and time‐lag of catchments were accounted for in calculating the indicators on a range of durations up to 30 days preceding a flood. Relationships between flood occurrence on 488 river basins and CTCs were explored using 73 catalogues developed within COST733 Action, all defined from automatic algorithms using ERA‐40 data. Results showed that at the river basin scale, some CTs have significant, positive frequency anomalies with flood occurrence. At the scale of Europe, the same CTs showed the strongest links with flood occurrence. The number of classes of CTCs is of lesser importance than the algorithm used, and depending whether global frequency or persistence of CT was analysed could give contrasting results. Results obtained from an automatically derived Grosswetterlagen classification were consistent with previous research, but performance was lower than that of other automatic algorithms (e.g. WLKC and SANDRAS). Results showed seasonal variation, possibly highlighting the differences in flood generation mechanisms in different regions and seasonal CT frequency. Copyright © 2010 John Wiley & Sons, Ltd.
Cobalt‐Catalyzed Cross‐Coupling Reactions of Aryl Halides
Authors: Gosmini Corinne , Moncomble Aurélien
Published: October 2010

Cobalt‐catalyzed carbon–carbon bond‐forming reactions are an indispensable class of reactions in organic synthesis. This economical and ecologically attractive catalyst could replace, in some cases, the well‐etablished, expensive palladium and toxic nickel catalytic systems that have dominated the field for many years. Cobalt‐catalyzed protocols tolerate various functional groups and present a wide range of reactivity. Moreover, these efficient reactions are very easy to carry out without complex ligands under varied conditions. This review intends to shed light on the fact that cobalt‐catalyzed cross‐coupling reactions offer an excellent alternative to the usual catalysts. Moreover, these methodologies are sometimes superior, especially for reactions involving alkyl halides.
FOSTERING EDUCATIONAL ENROLMENT THROUGH SUBSIDIES: THE ISSUE OF TIMING
Authors: Fiorini Mario
Published: October 2010

The purpose of this paper is to build a dynamic structural model of educational choices in which cognitive skills shape decisions. The model is estimated by maximum likelihood using cohort data where individuals are observed from birth to the middle of their working life. These data are unique in that they include cognitive skills test scores collected as early as age 7. We then investigate how alternative policies foster educational enrolment. In particular, we simulate the effect of two subsidies different in the timing of disbursement. The first consists of grants assigned directly to individuals aged between 16 and 18. The second is assigned to the parents earlier on, when the cohort is still in its childhood. The latter subsidy affects cognitive skills accumulation and in turn educational choices. Our results suggest that a grant fosters enrolment at the lowest cost but the parental income subsidy generates more welfare as measured by a class of social welfare functions. Nevertheless, these differences in costs and welfare are small. Overall, the results reinforce the view that government investments in cognitive skill accumulation during childhood are worthwhile. However, the results also indicate that such investments should be well structured to ensure a high return. Copyright © 2010 John Wiley & Sons, Ltd.
Toxicity and recovery in the pregnant mouse after gestational exposure to the cyanobacterial toxin, cylindrospermopsin
Authors: Chernoff N. , Rogers E. H. , Zehr R. D. , Gage M. I. , Malarkey D. E. , Bradfield C. A. , Liu Y. , Schmid J. E. , Jaskot R. H. , Richards J. H. , Wood C. R. , Rosen M. B.
Published: October 2010

Cylindrospermopsin (CYN) is a tricyclic alkaloid toxin produced by fresh water cyanobacterial species worldwide. CYN has been responsible for both livestock and human poisoning after oral exposure. This study investigated the toxicity of CYN to pregnant mice exposed during different segments of gestation. The course of recovery and individual responses to the toxin were evaluated. Adverse effects of CYN were monitored up to 7 weeks post‐dosing by clinical examination, histopathology, biochemistry and gene expression. Exposure on gestational days (GD) 8–12 induced significantly more lethality than GD13–17 exposure. Periorbital, gastrointestinal and distal tail hemorrhages were seen in both groups. Serum markers indicative of hepatic injury (alanine amino transferase, aspartate amino transferase and sorbitol dehydrogenase) were increased in both groups; markers of renal dysfunction (blood urea nitrogen and creatinine) were elevated in the GD8–12 animals. Histopathology was observed in the liver (centrilobular necrosis) and kidney (interstitial inflammation) in groups exhibiting abnormal serum markers. The expression profiles of genes involved in ribosomal biogenesis, xenobiotic and lipid metabolism, inflammatory response and oxidative stress were altered 24 h after the final dose. One week after dosing, gross, histological and serum parameters had returned to normal, although increased liver/body weight ratio and one instance of gastrointestinal bleeding was found in the GD13–17 group. Gene expression changes persisted up to 2 weeks post‐dosing and returned to normal by 4 weeks. Responses of individual animals to CYN exposure indicated highly significant inter‐animal variability within the treated groups. Copyright © 2010 John Wiley & Sons, Ltd.
A microfluidic positioning chamber for long‐term live‐cell imaging
Authors: Hanson Lindsey , Cui Lifeng , Xie Chong , Cui Bianxiao
Published: October 2010

We report a microfluidic positioning chamber (MPC) that can rapidly and repeatedly relocate the same imaging area on a microscope stage. The “roof” of the microfluidic chamber was printed with serials of coordinate numbers that act as positioning marks for mammalian cells that grow attached to the “floor” of the microfluidic chamber. MPC cell culture chamber provided a simple solution for tracking the same cell or groups of cells over days or weeks. The positioning marks were used to register time‐lapse images of the same imaging area to single‐pixel accuracy. Using MPC cell culture chamber, we tracked the migration, division, and differentiation of individual PC12 cells for over a week using bright field and fluorescence imaging. Microsc. Res. Tech., 2010. © 2010 Wiley‐Liss, Inc.
In vivo optical imaging of early‐stage apoptosis in mouse brain after transient cerebral ischemia
Authors: Liu Ning , Deguchi Kentaro , Shang Jingwei , Zhang Xuemei , Tian Fengfeng , Yamashita Toru , Ohta Yasuyuki , Ikeda Yoshio , Matsuura Tohru , Abe Koji
Published: October 2010

Apoptosis is one of the mechanisms contributing to neuronal degeneration in ischemic stroke. In vivo imaging of annexin V (A5) was performed at 12 hr, 24 hr, 48 hr, and 4 days after 90‐min transient middle cerebral artery occlusion (tMCAO) in mice with a fluorescent protein Cy5.5. Immunohistochemistry for heat shock protein 70 (HSP70), A5, and TUNEL were also performed with brain sections after the tMCAO. In vivo fluorescence was strongly observed at 48 hr over the head, especially with removal of both head skin and skull bone. Zonal ex vivo fluorescent signals were surrounding the ischemic core, and double‐positive cells with Cy5.5/exogenous A5 antibody were found in this area. HSP70 was observed at the peak time of 24 hr; A5 became detectable at 12 hr, with increasing numbers until 48 hr. The number of TUNEL‐positive cells increased at 24 hr and retained the high level until 4 days, showing a dissociating temporal pattern with A5. Double‐positive cells for A5/TUNEL reached their peak at 48 hr. All the data suggest that some cells still have a chance to be rescued for a long period after acute cerebral ischemia. The in vivo Cy5.5 fluorescence representing A5 signal spatially surrounding the ischemic core temporally detects an early‐stage apoptosis after cerebral ischemia. © 2010 Wiley‐Liss, Inc.
Redox proteomics in aging rat brain: Involvement of mitochondrial reduced glutathione status and mitochondrial protein oxidation in the aging process
Authors: Perluigi M. , Di Domenico F. , Giorgi A. , Schininà M.E. , Coccia R. , Cini C. , Bellia F. , Cambria M.T. , Cornelius C. , Butterfield D.A. , Calabrese V.
Published: October 2010

Increasing evidence supports the notion that increased oxidative stress is a fundamental cause in the aging process and in neurodegenerative diseases. As a result, a decline in cognitive function is generally associated with brain aging. Reactive oxygen species (ROS) are highly reactive intermediates, which can modify proteins, nucleic acids, and polyunsaturated fatty acids, leading to neuronal damage. Because proteins are major components of biological systems and play key roles in a variety of cellular functions, oxidative damage to proteins represents a primary event observed in aging and age‐related neurodegenerative disorders. In the present study, with a redox proteomics approach, we identified mitochondrial oxidatively modified proteins as a function of brain aging, specifically in those brain regions, such as cortex and hippocampus, that are commonly affected by the aging process. In all brain regions examined, many of the identified proteins were energy‐related, such as pyruvate kinase, ATP synthase, aldolase, creatine kinase, and α‐enolase. These alterations were associated with significant changes in both cytosolic and mitochondrial redox status in all brain regions analyzed. Our finding is in line with current literature postulating that free radical damage and decreased energy production are characteristic hallmarks of the aging process. In additon, our results further contribute to identifying common pathological pathways involved both in aging and in neurodegenerative disease development. © 2010 Wiley‐Liss, Inc.
Induction of neuronal cell death by paraneoplastic Ma1 antigen
Authors: Chen Huai‐Lu , D'Mello Santosh R.
Published: October 2010

Paraneoplastic Ma1 (PNMA1) is a member of a family of proteins involved in an autoimmune disorder called paraneoplastic neurological syndrome. Although it is widely expressed in brain, nothing is known about the function of PNMA1 in neurons. We find that PNMA1 expression is highest in the perinatal brain, a period during which developmentally regulated neuronal death occurs. PNMA1 expression increases in cerebellar granule neurons (CGNs) induced to die by low potassium (LK) and in cortical neurons following homocysteic acid (HCA) treament. Elevated PNMA1 expression is also observed in the degenerating striatum in two separate mouse models of Huntington's disease, the R6/2 transgenic model and the 3‐nitropropionic acid‐induced chemical model. Suppression of endogenous PNMA1 expression inhibits LK‐induced neuronal apoptosis. Ectopic expression of PNMA1 promotes apoptosis even in medium containing high potassium, a condition that normally ensures survival of CGNs. Deletion of the N‐terminal half of the PNMA1 protein abrogates its apoptotic activity, whereas deletion of the C‐terminal half renders the protein more toxic. Within the N‐terminal half, the ability to induce neuronal death depends on the presence of a BH3‐like domain. In addition to being necessary for apoptosis, the BH3‐like domain is necessary for self‐association of PNMA1. Apoptosis by PNMA1 expression is inhibited by overexpression of Bcl2, suggesting that PNMA1‐induced neuronal death may depend on the binding of a proapoptotic member of the Bcl2 family to the BH3 domain. Taken together, our results suggest that PNMA1 is a proapoptotic protein in neurons, elevated expression of which may contribute to neurodegenerative disorders. © 2010 Wiley‐Liss, Inc.
Central amplification and fibromyalgia: Disorder of pain processing
Authors: Petersel Danielle L. , Dror Vardit , Cheung Raymond
Published: October 2010

Fibromyalgia (FM), a complex chronic pain disorder affecting a heterogeneous patient population, is an area of active basic and clinical research. Although diagnostic criteria for FM have been available for 2 decades, there remains no definitive diagnostic and no consensus regarding its etiology. Accumulating evidence suggests the underlying cause of FM pain results from abnormal pain processing particularly in the central nervous system rather than from dysfunction in peripheral tissues where pain is perceived. In this review, we examine recent studies investigating abnormalities in central pain processing as a component of FM in both preclinical models of generalized muscle hypersensitivity and clinical research in patients with FM. We focus our discussion on two areas where strong evidence exists for abnormalities in sensory signaling: the reduction of descending control, including suppression of descending inhibitory pathways and/or enhancement of descending facilitatory pathways, and changes in key neurotransmitters associated with central sensitization. Finally, we discuss currently available pharmacological treatments indicated for the management of pain in FM patients, based on their proposed mechanism of action and efficacy. © 2010 Wiley‐Liss, Inc.
Extracellular calcium induces quiescence of the low‐frequency embryonic motor rhythm in the mouse isolated brainstem
Authors: Meillerais A. , Champagnat J. , Morin‐Surun M.P.
Published: October 2010

Although extracellular calcium ionic concentration ([Ca]o) is known to increase during late gestation and to drop after parturition, little is known about the influence of [Ca]o on fetal brain function. We have investigated the influence of [Ca]o, calcium‐sensing receptors/nonselective cation currents (CaSR/NSCC), and GABAergic inhibitions on maturation of brainstem‐spinal motor activities: the primary low‐frequency embryonic rhythm [LF; silent since embryonic day (E)16] and the fetal respiratory rhythm (RR; emerging at E14–E15). Using in vitro isolated brainstem‐spinal cord preparations of mice at different fetal and postnatal (P) stages (E16–P1), we demonstrate that reducing fetal [Ca]o from 1.2 mM to 0.7 mM at E16–E18 or blocking GABAA receptors at E16–P0 reactivates LF and reveals LF‐related disturbance of RR at E16–E18. This LF is stopped by adding gadolinium or spermidine (CaSR/NSCC agonists) at E18–P0 or GABAA receptor agonists at E16–E18. In contrast, [Ca]o–induced slowing of RR at E16–E18 is not reproduced by gadolinium and spermidine. We conclude that perinatal CaSR/NSCC and GABAA inhibition allow quiescence of the LF, thereby improving functional maturation of the RR. © 2010 Wiley‐Liss, Inc.
A single‐crystal Raman and infrared study of the nonlinear optical crystal MBANP
Authors: Bailey R. T. , Cruickshank F. R. , Dines T. J. , Sherwood N. , Tedford M. C.
Published: October 2010

Single‐crystal Raman and polycrystalline thin‐film infrared measurements have been obtained for the polar organic nonlinear optical material 2‐(α‐methylbenzylamino)‐5‐nitropyridine (MBANP). For comparison, thin‐film polycrystalline infrared measurements were also made on 2‐(α‐methylbenzylamino)‐3,5‐dinitropyridine (MBADNP). The long wavelength electronic absorption was measured in several solvents and as a thin solid film. The Raman spectra are dominated by three intense bands attributed to vibrations of the ring, the NO2 substituent, and the NH bond. The most intense scattering and absorption arose from the αbb component of the polarisability tensor. This implies that the most significant contribution to the transition polarisability arises from the electronic transition near 383 nm, polarised along the b‐axis of the crystal. The strongest bands in the infrared spectra are also associated with the same three bands, consistent with the predictions of the effective conjugation coordinate (ECC) theory, implying efficient electron–phonon coupling (or electronic delocalisation) in the conjugated system. DFT calculations of vibrational wavenumbers and eigenvectors were used to assign relevant vibrational features and to derive useful information about the molecular structure. This single‐crystal material is also a strong candidate for an efficient laser Raman converter with a large wavenumber shift of 3404 cm−1 and a high damage threshold. Copyright © 2010 John Wiley & Sons, Ltd.
Towards a global drylands observing system: Observational requirements and institutional solutions
Authors: Verstraete M. M. , Hutchinson C. F. , Grainger A. , Stafford Smith M. , Scholes R. J. , Reynolds J. F. , Barbosa P. , Léon A. , Mbow C.
Published: October 2010

Quantitative data on dryland changes and their effects on the people living there are required to support policymaking and environmental management at all scales. Data are regularly acquired by international, national or local entities, but presently exhibit specific gaps. Promoting sustainable development in drylands necessitates a much stronger integration, coordination and synthesis of available information. Space‐based remote sensing systems continue to play an important role but do not fulfill all needs. Dedicated networks and observing systems, operating over a wide range of scales and resolutions, are needed to address the key issues that concern decision‐makers at the scale of local communities, countries and the international community. This requires a mixture of ‘bottom–up’ and ‘top–down’ design principles, and multiple ownership of the resultant system. This paper reviews the limitations of current observing systems and suggests establishing a Global Drylands Observing System, which would capitalize on the achievements of systems already established to support the other Rio Conventions. This Global Drylands Observing System would provide an integrated, coherent entry point and user interface to a range of underlying information systems, identify and help generate missing information, propose a set of standards for the acquisition, archiving and distribution of data where these are lacking, evaluate the quality and reliability of these data and promote scientific research in these fields by improving access to data. The paper outlines the principles and main objectives of a Global Drylands Observing System and calls for renewed efforts to invigorate cooperation mechanisms between the many global environmental conventions. Copyright © 2010 John Wiley & Sons, Ltd.
Squeeze film characteristics between a sphere and a rough porous flat plate with micropolar fluids
Authors: Elsharkawy Abdallah A. , Al‐Fadhalah Khaled J.
Published: October 2010

The effects of surface roughness on the squeeze film characteristics between a sphere and flat plate covered with a thin porous layer are investigated in this paper. The sphere and the plate are separated with a non‐Newtonian lubricant of a micropolar fluid. The well‐established Christensen stochastic theory of hydrodynamic lubrication of rough surfaces is used to incorporate the effects of surface roughness into the Reynolds equation. The film pressure distribution is solved and other squeeze film characteristics, such as the load‐carrying capacity,and time–height relationship, are obtained. The results indicate that lubrication by a micropolar fluid will increase the load‐carrying capacity and lengthen the squeeze film time, regardless to the surface rough and porosity of the flat plate. It is also found that excessive permeability of the porous layer causes a significant drop in the squeeze film characteristics and minimises the effect of surface roughness. For the case of limited or no permeability, the azimuthal roughness is found to increase the load‐carrying capacity and squeeze time, whereas the reverse results are obtained for the case of radial roughness.
Explaining the joint effect of source credibility and negativity of information in two‐sided messages
Authors: Eisend Martin
Published: October 2010

By referring to different stages of an attribution process, this study examines how source credibility effects and opposing effects of negative information in two‐sided messages can be disentangled. The findings show that disclosure uniqueness (i.e., whether disclosures in a two‐sided message are given voluntarily or not) leads to both inferences on source credibility and inferences on product uniqueness. The inference on product uniqueness requires more cognitive effort on the part of the consumer than the inference on source credibility. Therefore, the effects of disclosures in two‐sided messages on brand attitudes depend on the cognitive load of consumers. Consumers make either an inference on the source or on both the source and the product. The results add to previous attribution research and the two‐sided message literature, showing that consumers under cognitive load can fail to make inferences on negative brand attributes in two‐sided messages. © 2010 Wiley Periodicals, Inc.
Greatly Enhanced Energy Density and Patterned Films Induced by Photo Cross‐Linking of Poly(vinylidene fluoride‐chlorotrifluoroethylene)
Authors: Chen Xiang‐Zhong , Li Zhi‐Wei , Cheng Zhao‐Xi , Zhang Ji‐Zong , Shen Qun‐Dong , Ge Hai‐Xiong , Li Hai‐Tao
Published: October 2010

Greatly enhanced energy density in poly(vinylidene fluoride‐chlorotrifluoroethylene) [P(VDF‐CTFE)] is realized through interface effects induced by a photo cross‐linking method. Being different from nanocomposites with lowered dielectric strength, the cross‐linked P(VDF‐CTFE)s possess a high breakdown field as well as remarkably elevated polarization, both of which contribute to the enhanced energy density as high as 22.5 J · cm−3. Moreover, patterned thin films with various shapes and sizes are fabricated by photolithography, which sheds new light on the integration of PVDF‐based electroactive polymers into organic microelectronic devices such as flexible pyroelectric/piezoelectric sensor arrays or non‐volatile ferroelectric memory devices.

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Tracking Explicit Chain Sequence in Kinetic Monte Carlo Simulations
Authors: Wang Lin , Broadbelt Linda J.
Published: October 2010

The execution of individual KMC events can become a major computational bottleneck in the simulation of sequences along chains using KMC because of complex data storage schemes required to record the sequence of each chain. The execution of a KMC event can be very time‐consuming because searching, moving, and modifying all the data detailing a chain to reflect the transformation as a result of a chemical reaction event can be computationally expensive. To address this issue, we developed a new data storage scheme for recording sequence, which can significantly improve calculation speed without affecting the information content of the calculations. By using the proposed data storage scheme, the computational time can be reduced significantly from 12 h to 4 min for our test reaction system.

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Staining ground sections of natural dry bone tissue for microscopy
Authors: de Boer H. H. , Aarents M. J. , Maat G. J. R.
Published: October 2010

The histological staining of bone tissue is of great value in identifying structural changes in human bone tissue when examined microscopically, and is therefore routinely used by clinical pathologists. However, for archaeological and other types of undecalcified dry bone tissue, histochemical staining is currently not widely used. The purpose of this paper is to describe a new method developed for the staining of undecalcified archaeological bone which may be a valuable addition to the palaeopathological toolkit. Sections were ground by hand and stained with haematoxylin and eosin. The microstructure and architecture of the stained sections become clearly visible without compromising total tissue envisioning. In addition, staining enhances differentiation between taphonomically affected and non‐affected bone tissue. This paper accordingly describes a reproducible stepwise method for the production of ground stained sections. An additional troubleshooting paragraph discusses the most often encountered problems and provides solutions. Copyright © 2010 John Wiley & Sons, Ltd.
Jekyll and Hyde: the role of the microenvironment on the progression of cancer
Authors: Allen Michael , Louise Jones J
Published: October 2010

It is now recognized that the host microenvironment undergoes extensive change during the evolution and progression of cancer. This involves the generation of cancer‐associated fibroblasts (CAFs), which, through release of growth factors and cytokines, lead to enhanced angiogenesis, increased tumour growth and invasion. It has also been demonstrated that CAFs may modulate the cancer stem cell (CSC) phenotype, which has therapeutic implications. The altered fibroblast phenotype also contributes to the development of an altered extracellular matrix (ECM), with synthesis of ECM isoforms rarely found in normal tissues, including tenascin‐C isoforms and the fibronectin EDA isoform. There is also emerging evidence of how the tensile strength of the tumour‐associated ECM may be modified and lead to altered signalling in tumour cells. The hypoxic environment of the tumour stimulates angiogenesis and also impacts on other aspects of cell signalling, including the c‐met pathway and lysyl oxidase‐mediated signalling, which can directly promote tumour cell invasion. The inflammatory infiltrate associated with many solid tumours also modulates tumour function, having both anti‐ and pro‐tumour effects. All of these components of the microenvironment provide potential targets for therapeutic attack, with a number of molecules already in clinical trials. It is also becoming evident that characterizing the tumour microenvironment can provide important prognostic and predictive information about tumours, independent of the tumour cell phenotype. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
A new era: melanoma genetics and therapeutics
Authors: Ko Justin M , Fisher David E
Published: October 2010

We have recently witnessed an explosion in our understanding of melanoma. Knowledge of the molecular basis of melanoma and the successes of targeted therapies have pushed melanoma care to the precipice of a new era. Identification of significant pathways and oncogenes has translated to the development of targeted therapies, some of which have produced major clinical responses. In this review, we provide an overview of selected key pathways and melanoma oncogenes as well as the targeted agents and therapeutic approaches whose successes suggest the promise of a new era in melanoma and cancer therapy. Despite these advances, the conversion of transient remissions to stable cures remains a vital challenge. Continued progress towards a better understanding about the complexity and redundancy responsible for melanoma progression may provide direction for anti‐cancer drug development. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Transparent copolyester/organoclay nanocomposites prepared by in situ intercalation polymerization: Synthesis, characterization, and properties
Authors: Tsai Yuhsin , Fan Cheng‐Hsing , Hung Chi‐Yuan , Tsai Fuu‐Jen
Published: October 2010

In this study, amorphous poly(ethylene terephthalate‐co‐1,3/1,4‐cyclohexylenedimethylene terephthalate) (PETG)/organoclay nanocomposites was synthesized by the in situ intercalation polymerization of terephthalic acid, ethylene glycol, 1,3/1,4‐cyclohexanedimethanol, and organoclay. The organoclay was obtained by modifying sodium montmorillonite (clay) with hexadecyl triphenylphosphonium bromide. The thermal, mechanical, optical, and gas barrier properties of these PETG nanocomposites with various organoclay contents (0–3 wt%) were discussed. The differential scanning calorimetry and X‐ray analyses revealed that all of the nanocomposites were amorphous. X‐ray diffraction and transmission electron micrographs showed that the organoclay was well dispersed in the polymer matrix, although some parts of the agglomerated layers remained on the scale of several hundreds of nanometers. The thermal stability and the mechanical property of the nanocomposites increased with organoclay content. The optical transmittances of nanocomposites that contained 0.5, 1, and 3 wt% of organoclay were 86.8%, 84.4%, and 77.4%, respectively. The oxygen transmission rate of the nanocomposite that contained 3 wt% of organoclay was about 50% of the PETG base polymer. POLYM. COMPOS., 2011. © 2010 Society of Plastics Engineers
Predicting the risk of pre‐eclampsia between 11 and 13 weeks' gestation by combining maternal characteristics and serum analytes, PAPP‐A and free β‐hCG
Authors: Goetzinger Katherine R. , Singla Ashima , Gerkowicz Sabrina , Dicke Jeffrey M. , Gray Diana L. , Odibo Anthony O.
Published: October 2010

Objective

To determine if a simplified model for predicting pre‐eclampsia (PEC) can be developed by combining first‐trimester serum analytes, pregnancy‐associated plasma protein A (PAPP‐A) and free beta human chorionic gonadotrophin (β‐hCG), and maternal characteristics.

Methods

A retrospective cohort study of patients seen for first‐trimester aneuploidy screening from 2003 to 2009. The 5th, 10th, 90th, and 95th percentiles for the analyte multiples of the medians (MoMs) for our population were determined and evaluated for association with PEC. Univariate and backward stepwise logistic regression analyses were performed and the area under the receiver operating characteristic (ROC) curves [area under curve (AUC)] used to determine the best models for predicting PEC.

Results

Among 4020 women meeting the inclusion criteria, outcome data was available for 3716 (93%). There were 293 cases of PEC. The final model identified a history of pre‐gestational diabetes [aOR 2.6, 95% confidence interval (CI) 1.7–3.9], chronic hypertension (cHTN) (aOR 2.6, 95% CI 1.7–3.9), maternal body mass index (BMI) > 25 (aOR 2.5, 95% CI 1.9–3.4), African American race (aOR 1.8, 95% CI 1.3–2.6), and PAPP‐A MoM < 10th percentile (aOR 1.6, 95% CI 1.1–2.4) to be significant predictors of PEC (AUC = 0.70, 95% CI 0.65–0.72).

Conclusion

Low first‐trimester PAPP‐A levels are associated with the development of PEC; however, the model was only modestly efficient in its predictive ability. Copyright © 2010 John Wiley & Sons, Ltd.
Production, cellular structure and thermal conductivity of microcellular (methyl methacrylate)–(butyl acrylate)–(methyl methacrylate) triblock copolymers
Authors: Reglero Ruiz Jose Antonio , Saiz‐Arroyo Cristina , Dumon Michel , Rodríguez‐Perez Miguel A , Gonzalez Leo
Published: October 2010

Microcellular foaming of a (methyl methacrylate)–(butyl acrylate)–(methyl methacrylate) triblock copolymer was carried out by means of supercritical CO2 in a single‐step process. The experiments were performed at 40 °C using a pressure of 300 bar (30 MPa) during 24 h. The depressurization times were modified from 2 to 30 min, leading to cell sizes from 10 to 100 µm, and relative densities from 0.11 to 0.17. It was found that the key parameter to control cell size and density was depressurization time: longer depressurization times generated larger cell sizes and lower densities. The thermal conductivity of these materials was measured using the transient plane source technique, and it was found that this decreased as the density was reduced. Various models for the prediction of thermal conductivity by conduction were tested. It was found that all the models underestimated the experimental results due to a significant contribution of radiation heat flow for these materials. Copyright © 2010 Society of Chemical Industry
Preparation and characterization of polyimide/modified layered double hydroxide nanocomposites
Authors: Ahn Jinhee , Han Mijeong , Ha Chang‐Sik
Published: October 2010

Polyimide (PI)/modified layered double hydroxide (m‐LDH) nanocomposites were prepared in this study. For this work, m‐LDHs were prepared from layered double hydroxides (LDHs) through an anionic exchange reaction with pyromellitic dianhydride (PMDA), succinic acid or terephthalic acid. PMDA and 4,4′‐oxydianiline were used to make the poly(amic acid) precursor for PI. X‐ray diffraction and transmission electron microscopy measurements confirmed that the PMDA‐modified LDH (PMH) and terephthalic acid‐modified LDH (TMH) were well dispersed in the PI matrix. For the succinic acid‐modified LDH, some of the LDH was intercalated with the succinic acid molecules but most maintained its original structure. Thus, the PI/PMH and PI/TMH nanocomposites exhibited improved mechanical, thermal and electrical properties compared to pure PI. The PMH has aromatic groups and is expected to have better π–π interactions with the PI chains than the other m‐LDHs. Thus, the PI/PMH nanocomposites exhibited the best properties among the nanocomposites investigated. Copyright © 2010 Society of Chemical Industry