bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Better Corporate Social Responsibility Disclosure on the Cost of Equity Capital
Authors: Reverte Carmelo
Published: June 2011

In this paper, we provide evidence on the impact of the quality of corporate social responsibility (CSR) reporting on the cost of equity capital for a sample of Spanish listed firms. We aim to verify whether firms with higher CSR disclosure ratings enjoy significantly lower costs of equity capital, after controlling for the well‐known Fama and French risk factors (i.e. beta, market‐to‐book, and size). Consistent with our main hypothesis, we find a significant negative relationship between CSR disclosure ratings and the cost of equity capital. We also obtain that the negative relationship between CSR reporting quality and the cost of equity capital is more pronounced for those firms operating in environmentally sensitive industries. Our findings contribute to the debate on whether CSR activities are value‐enhancing or value‐neutral by showing that improved CSR can enhance firm value by reducing the firm's cost of equity capital. This implies that CSR reporting is a part of a firm's communication tools in order to decrease information asymmetries between managers and investors. In other words, mandatory social responsibility reporting is called for in order to produce a more precise valuation of a firm. Copyright © 2011 John Wiley & Sons, Ltd and ERP Environment.
Evaluation of the pKa values and ionization sequence of bumetanide using 1H and 13C NMR and UV spectroscopy
Authors: Song Benben , Galande Amit K. , Kodukula Krishna , Moos Walter H. , Miller Susan M.
Published: June 2011

Non‐thiazide loop diuretics such as bumetanide and furosemide are well‐established medicaments, with varying substituents that alter their chemical properties in ways that affect biological parameters, including biodistribution, efficacy, and safety. However, literature data supporting the assignment of pKa values and ionization sequence of bumetanide are limited. The present study summarizes available literature data and then characterizes nuclear magnetic resonance (NMR) and ultraviolet (UV) spectral changes over a range of pH values to delineate the apparent sequence of deprotonations. Three macroscopic pKa values, 1.44, 3.74, and 10.37, were determined in water via pH titration experiments monitored by 1H NMR. Both 1H and 13C analyses support assignment of the lowest pKa value to the anilinium ion, as described for another diuretic, piretanide. However, UV data suggest that initial deprotonation of the benzoic acid competes to some extent with deprotonation of the anilinium ion, such that both pathways may operate simultaneously in an aqueous environment. Thus, the observed pKa values likely represent the macroscopic averages of the two competing deprotonation sequences. Calculated pKa values for bumetanide, piretanide, and model compounds are contrary to the deprotonation sequence we and others have determined experimentally, which is not surprising given the complicated factors driving the acid–base properties of these molecules. Drug Dev Res 72: 416–426, 2011. © 2011 Wiley‐Liss, Inc.
Synapses on demand require dendrites at the ready: How defining stages of dendritic development in vitro could inform studies of behaviorally driven information storage in the brain
Authors: Withers Ginger S. , Wallace Christopher S. , Gibbs Elizabeth M. , Emery Isaac R. , Applegate Marja L.
Published: June 2011

Bill Greenough's work provides a framework for thinking about synaptogenesis not only as a key step in the initial wiring of neural systems according to a species typical plan (i.e., experience‐expectant development), but also as a mechanism for storing information based an individual's unique experience over its lifetime (i.e., experience‐dependent plasticity). Analysis of synaptic development in vitro brings a new opportunity to test the limits of expectant‐expectant development at the level of the individual neuron. We analyzed dendritic growth, synapse formation, and the development of specialized cytoplasmic microdomains during development in cultured hippocampal neurons, to determine if the timing of each of these events is correlated. Taken together, the findings reported here support the hypotheses that (1) dendritic development is rate limiting in synapse formation and (2) synaptic circuits are assembled in a step‐wise fashion consistent with a stage‐specific shift from genomically pre‐programmed to activity‐dependent mechanisms. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 53:443–455, 2011.
A combination of enhancer/silencer modules regulates spatially restricted expression of cadherin‐7 in neural epithelium
Authors: Prasad Maneeshi S. , Paulson Alicia F.
Published: June 2011

The spatially restricted expression of cadherin‐7 to the intermediate domain of the neural epithelium and in migrating neural crest cells during early neural development is potentially regulated by multiple signaling inputs. To identify the regulatory modules involved in regulation of cadherin‐7, evolutionary conserved non‐coding sequences in the cadherin‐7 locus were analyzed. This led to the identification of an evolutionary conserved region of 606 bp (ECR1) that together with the cadherin‐7 promoter recapitulates endogenous cadherin‐7 expression in intermediate neural tube, spinal motor neurons, interneurons, and dorsal root ganglia. Deletion analysis of ECR1 revealed a 19‐bp block that is essential for ECR1 enhancer activity, while two separate blocks of 10 and 12 bp were found to be essential for ECR1 silencer activity in the dorsal and ventral neural epithelium, respectively. Together, these data provide an insight into tissue‐specific regulatory regions that might be involved in regulation of cadherin‐7 gene expression. Developmental Dynamics 240:1756–1768, 2011. © 2011 Wiley‐Liss, Inc.
The Role of Regional Governments in Climate Change Policy
Authors: Galarraga Ibon , Gonzalez‐Eguino Mikel , Markandya Anil
Published: June 2011

Climate change is one of the greatest challenges facing us, and it requires urgent policy action. Although climate change policies are mainly being discussed at international level by means of the United Nations Conventions and the Kyoto Protocol, the bulk of the impact will be felt at regional and local level. Regional and local governments are thus important actors. Moreover, regional governments in many parts of the world hold a wide range of the competences to implement policy actions for both adaptation and mitigation. This paper illustrates the important role of regions in climate policies and considers many of the policy instruments being designed and implemented. The paper describes 23 leading regions in climate policy. Finally, the case of Basque climate policy is described as an example of an industrial region in Europe where the degree of decentralization is significant. Copyright © 2011 John Wiley & Sons, Ltd and ERP Environment.
Long‐term conjugated linoleic acid supplementation in humans – effects on body composition and safety
Authors: Jutzeler van Wijlen Remo P.
Published: June 2011

In our contemporary adipogenic environment even modest improvements in body fat mass could be of relevance. In the last years animal and human studies have investigated the potential benefit of CLA on body composition. However, inconclusive results are often derived from short‐term studies. Long‐term intervention trials with supplemental CLA on body composition have not been reviewed exclusively up to now. Therefore, the objective of this study was to review the evidence of prolonged CLA supplementation as well as its influence on body composition in humans, and to summarize results from safety assessments of CLA intake. A literature search was performed to find intervention trials with CLA supplementation and its effects on body composition, as well as on insulin sensitivity. Only prolonged (≥12 wk) studies on body composition were included. The investigated studies indicate a modest reduction and/or prevention of regain of body fat in overweight/obese subjects. Results on the influence of CLA on insulin sensitivity are inconsistent, with newer data rather adding to the safety of CLA. Impaired insulin sensitivity by CLA remains a safety concern, yet is seemingly restricted to diabetic subjects and single‐isomer application. A meta‐a2 lysis of extended studies only is warranted to quantitatively evaluate the effects of CLA on body composition. Future research may elucidate if CLA should be considered as a marginal missing, semi‐essential nutrient in our present diet.
Palladium‐Catalyzed Direct Arylations of Five‐Membered Heteroarenes Bearing N‐Monoalkylcarboxamide Substituents
Authors: Laidaoui Nouria , Roger Julien , Miloudi Abdellah , El Abed Douniazad , Doucet Henri
Published: June 2011

The palladium‐catalyzed direct arylation of furan, thiophene, pyrrole, or pyrazole derivatives bearing CONHR substituents on C2, C3, or C5 with aryl bromides was studied. The use of KOAc as the base, DMAc as the solvent, and PdCl(C3H5)(dppb) as the catalyst was found to give regioselectively and without decarbamoylation the arylated heteroaromatics. Under these conditions, the amide substituent on the heteroaromatic does not act as a directing group. A wide range of functional groups such as acetyl, formyl, ester, nitrile, trifluoromethyl, and fluoro on the aryl bromide is tolerated.
The Bacterial Lectin FimH, a Target for Drug Discovery – Carbohydrate Inhibitors of Type 1 Fimbriae‐Mediated Bacterial Adhesion
Authors: Hartmann Mirja , Lindhorst Thisbe K.
Published: June 2011

Adhesion is a prerequisite for bacteria to colonize cell surfaces. To accomplish cellular adhesion, many bacteria use carbohydrate‐specific lectins, which are expressed as part of capillary protein appendages expanding from their surface, called fimbriae or pili. For bacteria, colonization of cell surfaces offers advantageous conditions to persist and multiply. For the host, however, bacterial colonization can be affiliated with severe health problems such as inflammation. Therefore, to combat bacterial adhesion and inflammatory diseases, investigation of the molecular and biophysical details of the relevant lectin–carbohydrate interactions is important. Understanding molecular carbohydrate recognition can lead to the development of high‐affinity inhibitors of bacterial lectins. That way, interfering with the bacterial attachment to surfaces proves the vision of an antiadhesion therapy, among others, against uropathogenic E. coli (UPEC). One of the most important and best investigated bacterial lectins is the mannose‐specific protein FimH, which is expressed on the tips of type 1 fimbriae. During the last 30 years, many natural as well as synthetic mannosidic ligands of FimH have been designed and tested for their inhibitory potencies. We report key results and comment on key problems and perspectives of this research.
Dual Secondary Amine/N‐Heterocyclic Carbene Catalysis in the Asymmetric Michael/Cross‐Benzoin Cascade Reaction of β‐Oxo Sulfones with Enals
Authors: Enders Dieter , Grossmann André , Huang He , Raabe Gerhard
Published: June 2011

Polyfuncionalized cyclopentanones with three contiguous stereogenic centers were formed in good to excellent yields and stereoselectivities by utilizing a secondary amine/N‐heterocyclic carbene catalytic system in the reaction of β‐oxo sulfones with unsaturated aldehydes. In addition, the influence of the catalysts on the diastereoselectivity of the final product was studied by 1H NMR spectroscopy.
Are sexualized women complete human beings? Why men and women dehumanize sexually objectified women
Authors: Vaes Jeroen , Paladino Paola , Puvia Elisa
Published: June 2011

Focusing on the dehumanization of sexually objectified targets, study 1 tested the extent to which objectified and non‐objectified male and female publicity photos were associated with human compared to animal concepts. Results confirmed the hypothesis that, among all targets, only objectified women were associated with less human concepts. This pattern of results emerged for both male and female participants but likely for different reasons. Study 2 directly looked at female and male participants' affinity with sexually objectified women. Results indicated that the more women distanced themselves from sexually objectified women the more they dehumanized them, whereas men's sexual attraction moderated their tendency to dehumanize female targets. In study 3, this latter motivation was operationalized as the activation of a sex goal and showed to trigger man's but not woman's dehumanization of female targets. Overall, the present set of studies show that only sexually objectified women are dehumanized by both men and women but for different reasons. Whereas sexual attraction shifts a men's focus of a female target away from her personality onto her body triggering a dehumanization process, women are more inclined to dehumanize their sexually objectified counterparts the more they distance themselves from these sexualized representations of their gender category. Copyright © 2011 John Wiley & Sons, Ltd.
Highly Efficient and Stable Palladium Nanoparticles Supported on an Ionic Liquid Silica SolGel Modified Electrode
Authors: Safavi A. , Banazadeh A. R.
Published: June 2011

A carbon ionic liquid electrode modified with a thin layer of silica solgel containing phosphinite ionic liquid was prepared for deposition of palladium nanoparticles. Palladium nanoparticles were formed easily by simple contact of the modified electrode with palladium chloride solution. The novel material overcomes the shortcomings of conventionally modified electrodes with a thin layer of silica solgel, due to the existence of ionic liquid in silica matrix. A crack‐free solgel matrix was obtained and also, the uniform porous structure of the ionic liquid‐solgel matrix resulted in a fast mass transport and increased ionic conductivity. The electrode exhibits high electrocatalytic effects towards hydrazine and ascorbic acid. It is very stable against repetitive cycling in the applied potential window.
Tract‐based magnetic resonance spectroscopy of the cingulum bundles at 7 T
Authors: Mandl René C.W. , van den Heuvel Martijn P. , Klomp Dennis W.J. , Boer Vincent O. , Siero Jeroen C.W. , Luijten Peter R. , Hulshoff Pol Hilleke E.
Published: June 2011

The cingulum bundle is a white matter fiber bundle in the human brain that is believed to be implicated in various neurological and psychiatric diseases. Subtle disease‐related differences in metabolite concentrations in the cingulum tracts that may underlie these diseases may be detected using MR spectroscopic information. However, to date, limited signal to noise and lack of spatial resolution have prevented a reliable and reproducible measurement of metabolites in the cingulum bundle in vivo. Here we propose a new method that combines MR spectroscopic imaging at 7 T with fiber tracking to select only those MR spectroscopy voxels that are actually part of the cingulum bundles. The spectra of the selected spectroscopy voxels are processed per voxel and then combined yielding one spectrum at high spectral resolution for each cingulum bundle. In this way sensitivity is increased, as large parts of the cingulum are included while partial volume effects with both gray matter and white matter from other tracts is kept to a minimum. Three healthy volunteers were scanned to assess the feasibility of the method. For all three healthy volunteers spectra for the left and right cingulum tracts were computed, partial volume fractions calculated and metabolite fractions were quantified yielding similar results suggesting that tract‐based MR spectroscopy allows us to study metabolic concentrations of individual white matter fiber bundles with high sensitivity and high specificity. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.
Constituents of the Endophytic Fungus Annulohypoxylon boveri var. microspora BCRC 34012
Authors: Cheng Ming‐Jen , Wu Ming‐Der , Hsieh Sung‐Yuan , Hsieh Ming‐Tsuen , Chen Ih‐Sheng , Yuan Gwo‐Fang
Published: June 2011

A new azaphilone metabolite with a new substitution pattern, named annulohypoxylin (1), together with twelve known compounds, were isolated from the BuOH‐soluble fraction of the 95% EtOH extract of long‐grain rice (Oryza sativa) fermented with the endophytic fungus Annulohypoxylon boveri var. microspora (BCRC 34012). Annulohypoxylin (1) contains a dihydrobenzofuran‐2,4‐dione backbone, 1‐hydroxyoctyl side chain, and one γ‐lactone ring. Its structure was determined on the basis of extensive 1D‐ and 2D‐NMR analyses in combination with HR‐ESI‐MS. The relative configuration of 1 was confirmed by NOESY experiment. Other known compounds were identified by comparing their spectral data with those in the literature. All known compounds were isolated from this species for the first time.
Citropremide and Citropridone: A New Ceramide and a New Acridone Alkaloid from the Stem Bark of Citropsis gabunensis
Authors: Tsassi Béatrice Valerie , Hussain Hidayat , Geagni Albertine , Dongo Etienne , Ahmed Ishtiaq , Riaz Muhammad , Krohn Karsten
Published: June 2011

The structure elucidation and complete 1H‐ and 13C‐NMR assignments are reported for two new compounds: the ceramide citropremide (1), and the acridone alkaloid citropridone (2). Both of these secondary metabolites were isolated from the stem bark of Citropsis gabunensis. High‐resolution mass, IR and UV spectrometry, and NMR experiments including COSY, HMQC, and HMBC were used for the determination of the structures and NMR spectral assignments.
Copper‐Catalyzed Bis(methoxycarbonyl)carbene Reactions of α,β‐Unsaturated Carboxamides
Authors: Merey Gökçe , Anaç Olcay
Published: June 2011

The [Cu(acac)2]‐catalyzed reactions of α,β‐unsaturated carboxamides with dimethyl diazomalonate yielded dihydrofuran derivatives by a 1,5‐electrocyclic reaction at C(β), and butadiene derivatives by carbene addition reaction at C(α) (Schemes 4 and 5; Table). Phenyl substituents at the N‐atom of the amides seem to be effective on the reaction pathways (Table).
Isolation and Structural Elucidation of Novel Mycosporine‐Like Amino Acids as Alarm Cues in the Defensive Ink Secretion of the Sea Hare Aplysia californica
Authors: Kamio Michiya , Kicklighter Cynthia E. , Nguyen Linh , Germann Markus W. , Derby Charles D.
Published: June 2011

Three new mycosporine‐like amino acids (MAAs), aplysiapalythines A, B, and C (1, 2, and 3, resp.) were isolated from opaline, a glandular component of the defensive ink secretion of sea hares (Aplysia californica) collected from waters off southern California. Here, we report the structure of these MAAs determined by mass spectrometry and NMR data. These new MAAs are structurally related to two known MAAs that are also present in sea hare opaline, i.e., asterina 330 (4) and palythine (5), and for which we also provide detailed data here for comparison. The fact that three of the five MAAs that we identified from sea hare opaline are novel molecules is interesting given that this represents a relatively large addition to the current list of known MAAs. This is likely because most researchers have identified MAAs through HPLC with UV detection, which is imprecise given similarities in UV spectra for different MAAs. Our findings suggest that there is much greater diversity of MAAs than is currently known. Results published elsewhere show that 1, 2, and 4 are alarm cues for conspecific sea hares at natural concentrations, but 3 and 5 are not.
Cigarette smoking and risk of histological subtypes of epithelial ovarian cancer in the EPIC cohort study
Authors: Gram Inger T. , Lukanova Annekatrin , Brill Ilene , Braaten Tonje , Lund Eiliv , Lundin Eva , Overvad Kim , Tjønneland Anne , Clavel‐Chapelon Francoise , Chabbert‐Buffet Nathalie , Bamia Christina , Trichopoulou Antonia , Zylis Dimosthenis , Masala Giovanna , Berrino Franco , Galasso Rocco , Tumino Rosario , Sacerdote Carlotta , Gavrilyuk Oxana , Kristiansen Steinar , Rodríguez Laudina , Bonet Catalina , Huerta José María , Barricarte Aurelio , Sánchez Maria‐José , Dorronsoro Miren , Jirström Karin , Almquist Martin , Idahl Annika , Bueno‐de‐Mesquita H. Bas , Braem Marie , Onland‐Moret Charlotte , Tsilidis Konstantinos K. , Allen Naomi E. , Fedirko Veronika , Riboli E. , Kaaks Rudolf
Published: June 2011

New data regarding a positive association between smoking and risk of epithelial ovarian cancer (EOC), especially the mucinous tumor type, has started to emerge. The purpose of this study was to examine the association between different measures of smoking exposures and subtypes of EOC in a large cohort of women from 10 European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort is a multicenter prospective study initiated in 1992. The questionnaires included data about dietary, lifestyle, and health factors. Information about cigarette smoking was collected from individuals in all participating countries. We used Cox proportional hazard regression models to estimate hazard ratio (HR) of EOC overall and serous, mucinous, and endometroid histological subtypes, with 95% confidence intervals (CIs) associated with different measures of smoking exposures adjusting for confounding variables. Altogether 836 incident EOC cases were identified among 326,831 women. The tumors were classified as 400 serous, 83 mucinous, 80 endometroid, 35 clear cell, and 238 unspecified. Compared with never smokers, current smokers had a significantly increased risk for mucinous tumors [HR = 1.85 (95% CI 1.08–3.16)] and those smoking more than 10 cigarettes per day had a doubling in risk [HR = 2.25(95% CI 1.26–4.03)] as did those who had smoked less than 15 pack‐years of cigarettes [HR = 2.18 (95% CI 1.07–4.43)]. The results from the EPIC study add further evidence that smoking increases risk of mucinous ovarian cancer and support the notion that the effect of smoking varies according to histological subtype.
New role of the human equilibrative nucleoside transporter 1 (hENT1) in Epithelial‐to‐mesenchymal transition in renal tubular cells
Authors: Guillén‐Gómez Elena , Pinilla‐Macua Itziar , Pérez‐Torras Sandra , Choi Doo‐Sup , Arce Yolanda , Ballarín José A. , Pastor‐Anglada Marçal , Díaz‐Encarnación Montserrat M.
Published: June 2011

Epithelial‐to‐mesenchymal transition (EMT) is an important pro‐fibrotic event in which tubular epithelial cells are transformed into myofibroblasts. Nucleoside transporters (NT) are regulated by many factors and processes, some of which are involved in fibrosis, such as cytokines, inflammation, and proliferation. Equilibrative nucleoside transporter 1 (ENT1) has been proved to be the most widely expressed adenosine transporter. In that sense, ENT1 may be a key player in cell damage signaling. Here we analyze the role of human ENT1 (hENT1) in the EMT process in proximal tubular cells. Addition of the main inducer of EMT, the transforming growth factor‐β1, to HK‐2 cells increased hENT1 mRNA and protein level expression. ENT1‐mediated adenosine uptake was also enhanced. When cells were incubated with dipyridamole to evaluate the potential contribution of ENT1 to EMT by blocking its transport activity, EMT was induced. Moreover, the knock down of hENT1 with siRNA induced EMT and collagen production in HK‐2 cells. Kidneys isolated from ENT1 knockout mice showed higher levels of interstitial collagen and α‐SMA positive cells than wild‐type mice. Our results point to a new potential role of hENT1 as a modulator of EMT in proximal tubular cells. In this sense, hENT1 could be involved in renal protection processes, and the loss or reduced expression of hENT1 would lead to an increased vulnerability of cells to the onset and/or progression of renal fibrosis. J. Cell. Physiol. 227: 1521–1528, 2012. © 2011 Wiley Periodicals, Inc.
Two mutations impair the stability and function of ubiquitin‐activating enzyme (E1)
Authors: Lao Taotao , Chen Shuyang , Sang Nianli
Published: June 2011

Protein ubiquitination plays critical roles in the regulation of multiple cellular processes including cell proliferation, signal transduction, oncogenesis, and hypoxic response. TS20 is a Balb3T3‐derived cell line in which ubiquitination is inhibited by restrictive temperature. While TS20 has been used to elucidate the degradation of many important proteins including p53, p27, HIF‐1α, and ornithine decarboxylase, the molecular basis of its temperature sensitivity has not been fully determined. We cloned full‐length E1 cDNA from TS20. Sequencing analysis revealed two point mutations (nt736G to A and nt2313G to C) that lead to substitution of aa189A to T and aa714W to C, respectively. Transient transfection assays revealed that mutant E1 was less stable than its wild‐type counterpart, and restrictive temperature (39°C) accelerated its degradation. Under permissive temperature, reverting aa714C to W significantly improved E1 stability and activity. Under restrictive temperature, reverting of both substitutions was required to fully restore E1 stability. Similar results were observed when the mutants were expressed in non‐TS20 cells, indicating the mutations are sufficient for its temperature sensitive degradation observed in TS20 cells. Functionally, reverting aa714C to W was sufficient to facilitate the monoubiquitination of H2A and to support TS20 growth at 39°C. It also significantly improved the ubiquitination‐dependent disposal of HIF‐1α. Our data conclusively demonstrate that mutations introgenic to UVBE1 cause E1 instability, which leads to deficiency of E1 function. Our data establish the molecular basis for unambiguous interpretation of experimental data based on TS20 cells, and provide new insight into the structural determinants of E1 stability. J. Cell. Physiol. 227: 1561–1568, 2012. © 2011 Wiley Periodicals, Inc.
Lithium regulates keratinocyte proliferation via glycogen synthase kinase 3 and NFAT2 (nuclear factor of activated T cells 2)
Authors: Hampton Philip J. , Jans Ralph , Flockhart Ross J. , Parker Graeme , Reynolds Nick J.
Published: June 2011

Certain environmental factors including drugs exacerbate or precipitate psoriasis. Lithium is the commonest cause of drug‐induced psoriasis but underlying mechanisms are currently unknown. Lithium inhibits glycogen synthase kinase 3 (GSK‐3). As lithium does not exacerbate other T‐cell‐mediated chronic inflammatory diseases, we investigated whether lithium may be acting directly on epidermal keratinocytes by inhibiting GSK‐3. We report that lithium‐induced keratinocyte proliferation at therapeutically relevant doses (1–2 mM) and increased the proportion of cells in S phase of the cell cycle. Inhibition of GSK‐3 in keratinocytes by retroviral transduction of GSK‐binding protein (an endogenous inhibitory protein) or through a highly selective pharmacological inhibitor also resulted in increased keratinocyte proliferation. Nuclear factor of activated T cells (NFAT) is an important substrate for GSK‐3 and for cyclosporin, an effective treatment for psoriasis that inhibits NFAT activation in keratinocytes as well as in lymphocytes. Both lithium and genetic/pharmacological inhibition of GSK‐3 resulted in increased nuclear localization of NFAT2 (NFATc1) and increased NFAT transcriptional activation. Finally, retroviral transduction of NFAT2 increased keratinocyte proliferation whereas siRNA‐mediated knockdown of NFAT2 reduced keratinocyte proliferation and decreased epidermal thickness in an organotypic skin equivalent model. Taken together, these data identify GSK‐3 and NFAT2 as key regulators of keratinocyte proliferation and as potential molecular targets relevant to lithium‐provoked psoriasis. J. Cell. Physiol. 227: 1529–1537, 2012. © 2011 Wiley Periodicals, Inc.
Strong expression association between matriptase and its substrate prostasin in breast cancer
Authors: Bergum Christopher , Zoratti Gina , Boerner Julie , List Karin
Published: June 2011

Breast cancer tumorigenesis is accompanied by increased levels of extracellular proteases that are capable of remodeling the extracellular matrix as well as cleaving and activating growth factors and signaling receptors that are critically involved in neoplastic progression. Multiple studies implicate the membrane anchored serine protease matriptase (also known as MT‐SP1 and epithin) in breast cancer. The pro‐form of the GPI‐anchored serine protease prostasin has recently been identified as a physiological substrate of matriptase and the two proteases are co‐expressed in multiple healthy tissues. In this study, the inter‐relationship between the two membrane‐anchored serine proteases in breast cancer was investigated using breast cancer cell lines and breast cancer patient samples to delineate the association between matriptase and prostasin. We used Western blotting to determine the expression of matriptase and prostasin proteins in a panel of breast cancer cell lines and immunohistochemistry to assess the expression in serial sections from breast cancer tissue arrays. We demonstrate that the expression of matriptase and prostasin is closely correlated in breast cancer cell lines as well as in breast cancer tissue samples. Furthermore, matriptase and prostasin display a near identical spatial expression pattern in the epithelial compartment of breast cancer tissue. These data suggest that the matriptase–prostasin cascade might play a critical role in breast cancer. J. Cell. Physiol. 227: 1604–1609, 2012. © 2011 Wiley Periodicals, Inc.
Runx1 and C/EBPβ transcription factors directly up‐regulate P2X3 gene transcription
Authors: Ugarte Giorgia D. , Opazo Tatiana , Leisewitz Francisco , van Zundert Brigitte , Montecino Martin
Published: June 2011

Recent evidence indicates that transcription factor Runx1 modulates the expression of several phenotypic markers in dorsal root ganglia (DRGs) neurons, including the pain‐related P2X3 receptor. In several cell lineages C/EBP transcription factors interact with the Runx factor family members to jointly bind and activate transcription of target genes. Here, we examine whether these two transcription factors directly regulate P2X3 gene expression. Through in silico analyses of the first 2 kb of the P2X3 gene promoter we identified putative consensus‐binding sites for both Runx1 and C/EBPβ transcription factors. Transient over‐expression in PC12 cells of either Runx1 or C/EBPβ increases P2X3 gene promoter activity and co‐expression of both factors results in an additive stimulatory effect on the promoter function. Accordingly, chromatin immunoprecipitation assays demonstrate that both Runx1 and C/EBPβ bind to the P2X3 promoter in PC12 cells expressing this gene. Site‐directed mutagenesis of the proximal Runx1 and C/EBPβ consensus elements in the P2X3 promoter decrease Runx1‐ and C/EBPβ‐mediated transcriptional activity. Moreover, C/EBPβ‐mediated enhancement of the P2X3 promoter requires a functional Runx1 binding site. Altogether our results support a functional and coordinated role for Runx1 and C/EBPβ transcription factors during activation of P2X3 gene transcription. J. Cell. Physiol. 227: 1645–1652, 2012. © 2011 Wiley Periodicals, Inc.
Embryologic origin of endometriosis: Analysis of 101 human female fetuses
Authors: Signorile Pietro G. , Baldi Feliciano , Bussani Rossana , Viceconte Rosa , Bulzomi Pamela , D'Armiento Mariarosaria , D'Avino Alfredo , Baldi Alfonso
Published: June 2011

The etiology of endometriosis, a gynecological disease characterized by the presence of endometrial glands and stroma outside the uterine cavity, is still unknown. Our research group has recently demonstrated the presence of ectopic endometrium in human female fetuses at different gestational ages. In this manuscript we describe four new cases of fetal endometriosis found among a series of 52 female fetuses analyzed at autopsy. The anatomical localization of this ectopic endometrium, and its histological and immunohistochemical characteristics are depicted. We suggest that endometriosis is caused by dislocation of primitive endometrial tissue outside the uterine cavity during organogenesis. The clinical and pathological implications of these findings are discussed. J. Cell. Physiol. 227: 1653–1656, 2012. © 2011 Wiley Periodicals, Inc.
Pharmacokinetic analysis of plasma curves obtained after i.v. injection of the PET radioligand [11C] raclopride provides a likely explanation for rapid radioligand metabolism
Authors: Sestini Stelvio , Halldin Christer , Mansi Luigi , Castagnoli Antonio , Farde Lars
Published: June 2011

Positron emission tomography (PET) is an imaging technique that provides direct measurements of receptor binding in neurons. The present study was performed to find reasons for the common observation of rapid metabolism of receptor radioligands during time of a brain PET scan. To this aim, the 1‐h phase during which imaging‐data are acquired was evaluated by using a pharmacokinetic approach. The values of half‐lives, volumes of distribution, and dilution calculated for a set of metabolite corrected plasma curves of D2‐receptor radioligand [11C]raclopride (PETc) during 50 min after radioligand injection in tracer dose were compared with the reference values obtained from a set of plasma curves (REFc) during 30 h after i.v. infusion of unlabelled raclopride in pharmacological doses. We found that the half‐life of PETc correspond to the distribution half‐life of REFc. Accordingly, the distribution volume during the terminal phase of PETc (13.6 ± 10.8 L) was significantly lower than that during the terminal phase (82.2 ± 30.5 L) and at steady state (59.4 ± 20 L) for REFc, and the dilution of raclopride in body for PETc at 50 min was 38 L, whereas it was 1015 L for REFc at 30 h. The [11C]raclopride in plasma at 50 min was higher (10% of dose) than the value for unlabelled raclopride at 30 h (4%). We concluded that the kinetic behavior of the radiolabelled drug [11C]raclopride during the 1 h time of a PET corresponds to the distribution phase. The high percentage of [11C]raclopride in plasma during this phase is a likely reason for the observed rapid radioligand metabolism. J. Cell. Physiol. 227: 1663–1669, 2012. © 2011 Wiley Periodicals, Inc.
Cellular and molecular large‐scale features of fetal adipose tissue: Is bovine perirenal adipose tissue Brown1685
Authors: Taga Hajer , Chilliard Yves , Meunier Bruno , Chambon Christophe , Picard Brigitte , Zingaretti Maria C. , Cinti Saverio , Bonnet Muriel
Published: June 2011

Epidemiological and fetal programming studies point to the role of fetal growth in adult adipose tissue (AT) mass in large mammals. Despite the incidence of fetal AT growth for human health and animal production outcomes, there is still a lack of relevant studies. We determined the cellular and large‐scale‐molecular features of bovine fetal perirenal AT sampled at 110, 180, 210, and 260 days post‐conception (dpc) with the aim of identifying key cellular and molecular events in AT growth. The increase in AT weight from 110 to 260 dpc resulted from an increase in adipocyte volume and particularly adipocyte number that were concomitant with temporal changes in the abundance of 142 proteins revealed by proteomics. At 110 and 180 dpc, we identified proteins such as TCP1, FKBP4, or HSPD1 that may regulate adipocyte precursor proliferation by controlling cell‐cycle progression and/or apoptosis or delaying PPARγ‐induced differentiation. From 180 dpc, the up‐regulation of PPARγ‐induced proteins, lipogenic and lipolytic enzymes, and adipokine expression may underpin the differentiation and increase in adipocyte volume. Also from 180 dpc, we unexpectedly observed up‐regulations in the β‐subunit of ATP synthase, which is normally bypassed in brown AT, as well as in aldehyde dehydrogenases ALDH2 and ALDH9A1, which were predominantly expressed in mouse white AT. These results, together with the observed abundant unilocular adipocytes at 180 and 260 dpc, strongly suggest that fetal bovine perirenal AT has much more in common with white than with brown AT. J. Cell. Physiol. 227: 1688–1700, 2012. © 2011 Wiley Periodicals, Inc.
TRPV4 in the sensory organs of adult zebrafish
Authors: Amato V. , Viña E. , Calavia M.G. , Guerrera M.C. , LaurÀ R. , Navarro M. , De Carlos F. , Cobo J. , Germanà A. , Vega J.A.
Published: June 2011

TRPV4 is a nonselective cation channel that belongs to the vanilloid (V) subfamily of transient receptor potential (TRP) ion channels. While TRP channels have been found to be involved in sensing temperature, light, pressure, and chemical stimuli, TPRV4 is believed to be primarily a mechanosensor although it can also respond to warm temperatures, acidic pH, and several chemical compounds. In zebrafish, the expression of trpv4 has been studied during embryonic development, whereas its pattern of TPRV4 expression during the adult life has not been thoroughly analyzed. In this study, the occurrence of TRPV4 was addressed in the zebrafish sensory organs at the mRNA (RT‐PCR) and protein (Westernblot) levels. Once the occurrence of TRPV4 was demonstrated, the TRPV4 positive cells were identified by using immunohistochemistry. TPRV4 was detected in mantle and sensory cells of neuromasts, in a subpopulation of hair sensory cells in the macula and in the cristae ampullaris of the inner ear, in sensory cells in the taste buds, in crypt neurons and ciliated sensory neurons of the olfactory epithelium, and in cells of the retina. These results demonstrate the presence of TRPV4 in all sensory organs of adult zebrafish and are consistent with the multiple physiological functions suspected for TRPV4 in mammals (mechanosensation, hearing, and temperature sensing), but furthermore suggest potential roles in olfaction and vision in zebrafish. Microsc. Res. Tech., 2012. © 2011 Wiley Periodicals, Inc.
Adeno‐associated virus‐mediated expression of acid sphingomyelinase decreases atherosclerotic lesion formation in apolipoprotein E−/− mice
Authors: Leger Andrew J. , Mosquea Leocadia M. , Li Lingyun , Chuang WeiLien , Pacheco Joshua , Taylor Kristin , Luo Zhengyu , Piepenhagen Peter , Ziegler Robin , Moreland Rod , Urabe Akihiro , Jiang Canwen , Cheng Seng H. , Yew Nelson S.
Published: June 2011

Background

The secretory form of acid sphingomyelinase (ASM) is postulated to play a key role in the retention and aggregation of lipoproteins in the subendothelial space of the arterial wall by converting sphingomyelin in lipoproteins into ceramide. The present study aimed to determine whether the level of circulating ASM activity affects lesion development in mouse model of atherosclerosis.

Methods

Apolipoprotein E deficient (ApoE−/−) mice were injected intravenously with a recombinant adeno‐associated virus (AAV8‐ASM) that constitutively expressed high levels of human ASM in liver and plasma.

Results

Plasma sphingomyelin levels were reduced at early but not later time points after the administration of AAV8‐ASM despite persistently elevated circulating ASM. No change in serum lipoprotein levels was observed. Thirteen or 17 weeks after the administration of AAV8‐ASM, the amount of plaque formation in the aortic sinus was comparable to that of mice treated with a control AAV.

Conclusions

Unexpectedly, the lesion area of the entire aorta was reduced significantly in the AAV8‐ASM virus‐treated group. Hepatic expression and secretion of ASM into the circulation did not accelerate or exacerbate, but rather decreased, lesion formation in ApoE−/− mice. Thus, plasma ASM activity does not appear to be rate limiting for plaque formation during atherogenesis. Copyright © 2011 John Wiley & Sons, Ltd.
Intravenous injection of irradiated tumor cell vaccine carrying oncolytic adenovirus suppressed the growth of multiple lung tumors in a mouse squamous cell carcinoma model
Authors: Saito Aya , Morishita Naoya , Mitsuoka Chihomi , Kitajima Shunichi , Hamada Katsuyuki , Lee Kyung‐Mi , Kawabata Masato , Fujisawa Masato , Shirakawa Toshiro
Published: June 2011

Background

Although cancer therapy using replication‐selective oncolytic adenoviruses has been available for many years, its anti‐tumor efficacy is suboptimal as a result of low and nonspecific infectivity that depends on coxsackie adenovirus receptor expression of the target cancer and normal cells, and generation of an anti‐adenovirus neutralizing antibody. In addition, concerns of triggering a severe innate immune response against the adenovirus limit the systemic administration. We developed the carrier cell‐based oncolytic virus system (CBOVS) using irradiated tumor cells as carrier cells and concealing the adenovirus (Ad‐IAI.3B) inside to improve the specific infectivity. We investigated the anti‐tumor effect of CBOVS in a multiple lung tumor mouse model.

Methods

The ability of CBOVS to infect Ad‐IAI.3B to the target cancer cells was examined in vitro in the presence of anti‐adenovirus antibodies. To evaluate the systemic effect of CBOVS, we intravenously injected CBOVS into mice with lung tumors (KLN205 cell lines).

Results

CBOVS enhanced the infectivity of Ad‐IAI.3B to tumor cells in the presence of anti‐adenovirus antibodies in vitro. Intravenous injections of CBOVS produced an accumulation of the adenovirus in the lung‐bearing tumors and produced a strong anti‐tumor effect in vivo. Furthermore, lymphocytes collected from the CBOVS‐treated mice induced an increase in cytokines related to the Th1 response (interferon‐γ, interleukin‐12) by pulsing with KLN205.

Conclusions

These findings suggest that CBOVS could protect adenoviruses from neutralizing antibodies and systemically deliver them to lung tumors. Furthermore, CBOVS appears to have potential as a tumor cell vaccine that activates cytotoxic immunity against cancer cells. Copyright © 2011 John Wiley & Sons, Ltd.
On the way to understand antioxidants: chromanol and dimethoxyphenols gas‐phase acidities
Authors: Amorim Madeira Paulo J. , Faddoul Mohammed , Afonso Marta B. , Vaz Pedro D. , Fernandez M. Tereza , Leal João Paulo
Published: June 2011

Some antioxidant mechanisms displayed by several phenolic compounds relate with OH bond dissociation energy. One way for its determination, in the gas‐phase, relies on acidity measurements. Gas‐phase acidities were determined experimentally, applying the kinetic method, for chromanol and four dimethoxyphenols, and theoretically through quantum chemical DFT calculations for chromanol, six dimethoxyphenols and 3,4,5‐trimethoxyphenol. The experimental acidity order, 2,3‐dimethoxyphenol > 3,5‐dimethoxyphenol > 2,6‐dimethoxyphenol > 3,4‐dimethoxyphenol ≈ phenol > chromanol shows good agreement with the theoretical acidity order, 2,5‐dimethoxyphenol > 2,3‐dimethoxyphenol > 3,4,5‐trimethoxyphenol > 3,5‐dimethoxyphenol ≈ 2,4‐dimethoxyphenol > 2,6‐dimethoxyphenol > 3,4‐dimethoxyphenol > phenol > chromanol. These acidity trends were rationalized in terms of the substituent effects on the thermodynamic stabilities both of the parent phenols and the corresponding phenoxide ions. DFT calculations also evidenced the occurrence of intramolecular CH···O hydrogen bonds whenever there are vicinal substituents (either OH, O− or OCH3) which induce further stabilization of the geometries. Copyright © 2011 John Wiley & Sons, Ltd.
Molecular characterization of BK polyomavirus subtypes in renal transplant recipients in Brazil
Authors: Zalona Ana Carolina Jonard , Lopes Guilherme Santoro , Schrago Carlos Guerra , Gonçalves Renato Torres , Zalis Mariano Gustavo , Varella Rafael Brandão
Published: June 2011

BK polyomavirus (BKV) is highly prevalent in the world population. Different reports indicate that BKV subtypes and subgroups present an uneven geographical distribution which might be correlated with human migration. However, there is a lack of data on the BKV subtype distribution in the South American population. The occurrence of BKV subtypes and subgroups detected in 51 kidney transplant recipients in Rio de Janeiro, Brazil is described. According to genetic studies, the population in this region descends mainly from European or African immigrants, with a relatively low genetic background from the Amerindians. By sequencing the VP1 region of BKV, subgroups Ib1 and Ia of subtype I were found in 34 (67%) and 15 (29%), respectively, of samples, while subtype II was present in 2 (4%) of the samples. Subtypes III and IV were not detected. Phylogenetic analysis indicated similarities between Brazilian BKV subgroup Ia and East African lineages; and subgroup Ib‐1 with Asian and North American lineages, while subtype II samples were similar to sequences from Japan and the UK. This is the first report that describes distribution of BKV subtypes in South America. The high prevalence of BKV subgroup Ia probably reflects the high proportion of African descendants in this population. On the other hand, the predominance of subgroup Ib‐1 and the absence of Ib‐2 in an area with a high proportion of European ancestry was unexpected. Further studies in South American populations are needed to provide a better understanding of the epidemiology of BKV in this region. J. Med. Virol. 83:1401–1405, 2011. © 2011 Wiley‐Liss, Inc.
WU polyomavirus infection among children in South China
Authors: Zhuang Wan‐Li , Lu Xue‐Dong , Lin Guang‐Yu , Wu Yang , Lin Chuang‐Xing , Chen Pai‐Zhen , Xie Shu‐Xia , Zhang Na , Ma Lian
Published: June 2011

This study aimed at investigating the prevalence and clinical characteristics of children with respiratory infection by WU polyomavirus (WUPyV) in Southern China. Nasopharyngeal aspirate samples were collected from 771 children with acute respiratory tract infection admitted to hospital and 82 samples from healthy subjects for routine examination at the outpatient service at the Second Affiliated Hospital of Shantou University, Medical College from July 2008 to June 2009. WUPyV was detected by the polymerase chain reaction (PCR) and DNA sequencing. All WUPyV‐positive specimens were characterized further for nine viruses causing common respiratory infections, including inﬂuenza A and B, respiratory syncytial virus (RSV), parainfluenza virus (PIV) 1 and 3, human metapneumovirus, human bocavirus, adenovirus, and rhinovirus by PCR or real time (RT)‐PCR. Fifteen out of 771 specimens from patients with acute respiratory tract infection, but none from healthy subjects, were positive for WUPyV and the positivity rate was 2%. Patients with WUPyV infection were between 2 and 48 months of age, and nine of the patients were male while six female. Four out of 15 patients were co‐infected with RSV, one with adenovirus or rhinovirus, respectively. Patients with WUPyV infection displayed predominantly cough, moderate fever, and wheezing, and were diagnosed with pneumonia (n = 8), bronchiolitis (n = 4), upper respiratory tract infections (n = 2) and bronchitis (n = 1). One patient developed encephalitis. Therefore, WUPyV infection can cause acute respiratory tract infection with atypical symptoms, including severe complications, in children. J. Med. Virol. 83:1440–1445, 2011. © 2011 Wiley‐Liss, Inc.