bluuebunny/crossref_metadata_2025 huggingface dataset:
The approaches for manipulating mitochondrial proteome
Authors: Shokolenko Inna N. , Alexeyev Mikhail F. , LeDoux Susan P. , Wilson Glenn L.
Published: April 2010

Over the past decade a large volume of research data has accumulated which has established a fundamental role for mitochondria in normal cellular functioning, as well as in various pathologies. Mitochondria play a pivotal role in metabolism and energy production, and are one of the key players involved in programmed cell death. On the other hand, mitochondrial dysfunction is implicated, directly or indirectly in numerous pathological conditions including inherited mitochondrial disorders, diabetes, cardiovascular and neurodegenerative diseases, and a variety of malignancies. The ability to modulate mitochondrial function by altering the diverse protein component of this organelle may be of great value for developing future therapeutic interventions. This review will discuss approaches used to introduce proteins into mitochondria. One group of methods utilizes strategies aimed at expressing proteins from genes in the nucleus. These include overexpression of nuclear‐encoded mitochondrial proteins, allotopic expression, which is the re‐coding and relocation of mitochondrial genes to the nucleus for expression and subsequent delivery of their gene products to mitochondria, and xenotopic expression, which is the nuclear expression of genes coding electron transport chain components from distant species, for delivery of their products to mammalian mitochondria. Additionally, antigenomic and progenomic strategies which focus on expression of mitochondrially targeted nuclear proteins involved in the maintenance of mtDNA will be discussed. The second group of methods considered will focus on attempts to use purified proteins for mitochondrial delivery. Special consideration has been given to the complexities involved in targeting exogenous proteins to mitochondria. Environ. Mol. Mutagen., 2010. © 2010 Wiley‐Liss, Inc.
A compendium of human mitochondrial gene expression machinery with links to disease
Authors: Shutt Timothy E. , Shadel Gerald S.
Published: April 2010

Mammalian mitochondrial DNA encodes 37 essential genes required for ATP production via oxidative phosphorylation, instability or misregulation of which is associated with human diseases and aging. Other than the mtDNA‐encoded RNA species (13 mRNAs, 12S and 16S rRNAs, and 22 tRNAs), the remaining factors needed for mitochondrial gene expression (i.e., transcription, RNA processing/modification, and translation), including a dedicated set of mitochondrial ribosomal proteins, are products of nuclear genes that are imported into the mitochondrial matrix. Herein, we inventory the human mitochondrial gene expression machinery, and, while doing so, we highlight specific associations of these regulatory factors with human disease. Major new breakthroughs have been made recently in this burgeoning area that set the stage for exciting future studies on the key outstanding issue of how mitochondrial gene expression is regulated differentially in vivo. This should promote a greater understanding of why mtDNA mutations and dysfunction cause the complex and tissue‐specific pathology characteristic of mitochondrial disease states and how mitochondrial dysfunction contributes to more common human pathology and aging. Environ. Mol. Mutagen., 2010. © 2010 Wiley‐Liss, Inc.
Perceptual characteristics of tracheoesophageal speech production using the new indwelling Provox Vega voice prosthesis: A randomized controlled crossover trial
Authors: Ward Elizabeth C. , Hancock Kelli , Lawson Nadine , van As–Brooks Corina J.
Published: April 2010

Background.

The objective of this study was to determine if the design enhancements incorporated into the new Provox Vega Indwelling Voice prostheses result in any positive benefits in vivo.

Methods.

Using a randomized, crossover study design, 31 participants using tracheoesophageal speech postlaryngectomy completed a 3‐week trial of the Provox Vega and a comparator device. Main outcome measures included patient perceptions of vocal effort and quality using each device, and perceptual judgments of voice quality produced.

Results.

The majority of patients (72%) indicated the Provox Vega gave them overall better voice quality and 52% felt they required less effort to phonate. Voice samples produced with the Provox Vega were also perceived by listeners to be significantly (p < .05) less strained, easier to understand, produced with less effort, and the better speech sample overall.

Conclusion.

Results support that the aerodynamic improvements incorporated in the design of the new Provox Vega facilitate enhanced voice and speech qualities. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Mechanotransduction by endothelial cells is locally generated, direction‐dependent, and ligand‐specific
Authors: Chrétien Marc L. , Zhang Ming , Jackson Moira R. , Kapus Andras , Langille B. Lowell
Published: April 2010

Vascular endothelial cells display a wide panel of responses to changes in the shear stress that is exerted on them by blood flow. How sensory mechanisms convey information about flow conditions and how this information is integrated remains poorly understood. The issue is confounded by: (1) a large number of potential force sensors, (2) difficulties in differentiating these sensors from downstream sites of signal integration, and (3) the complexities inherent in understanding how forces are transmitted from the apical surface of the cell via the cytoskeleton to intracellular sites. As a consequence, neither the structures that sense force nor the nature of the forces that loads them have been clearly defined. In this study, we employed magnetic microspheres coated with ligands that bind integrin subsets (RGD peptides or type I collagen) or PECAM‐1 to discriminate the downstream signaling effects of different sensor molecules and mechanisms for how they are loaded. We found that application of force to these transmembrane molecules elicited biologically important signaling (ERK1/2, AKT, and GSK‐3β phosphorylation), and downstream biological responses that depended on the following two factors: (1) the ligand that transmitted force and (2) the direction in which force was applied. These findings indicate that ligands locally generate different shear‐induced responses in endothelium that depend on how force is delivered. J. Cell. Physiol. 224: 352–361, 2010. © 2010 Wiley‐Liss, Inc.
Adaptation to alkalosis induces cell cycle delay and apoptosis in cortical collecting duct cells: Role of aquaporin‐2
Authors: Rivarola Valeria , Flamenco Pilar , Melamud Luciana , Galizia Luciano , Ford Paula , Capurro Claudia
Published: April 2010

Collecting ducts (CD) not only constitute the final site for regulating urine concentration by increasing apical membrane Aquaporin‐2 (AQP2) expression, but are also essential for the control of acid–base status. The aim of this work was to examine, in renal cells, the effects of chronic alkalosis on cell growth/death as well as to define whether AQP2 expression plays any role during this adaptation. Two CD cell lines were used: WT‐ (not expressing AQPs) and AQP2‐RCCD1 (expressing apical AQP2). Our results showed that AQP2 expression per se accelerates cell proliferation by an increase in cell cycle progression. Chronic alkalosis induced, in both cells lines, a time‐dependent reduction in cell growth. Even more, cell cycle movement, assessed by 5‐bromodeoxyuridine pulse‐chase and propidium iodide analyses, revealed a G2/M phase cell accumulation associated with longer S‐ and G2/M‐transit times. This G2/M arrest is paralleled with changes consistent with apoptosis. All these effects appeared 24 h before and were always more pronounced in cells expressing AQP2. Moreover, in AQP2‐expressing cells, part of the observed alkalosis cell growth decrease is explained by AQP2 protein down‐regulation. We conclude that in CD cells alkalosis causes a reduction in cell growth by cell cycle delay that triggers apoptosis as an adaptive reaction to this environment stress. Since cell volume changes are prerequisite for the initiation of cell proliferation or apoptosis, we propose that AQP2 expression facilitates cell swelling or shrinkage leading to the activation of channels necessary to the control of these processes. J. Cell. Physiol. 224: 405–413, 2010. © 2010 Wiley‐Liss, Inc.
Inhibitive effects of Photofrin on cellular autophagy
Authors: Luo Shiming , Xing Da , Wei Yanchun , Chen Qun
Published: April 2010

Depending on the circumstances, autophagy can be either a protective or damaging cellular process. The role of autophagy in photodynamic therapy (PDT), a photo‐chemotherapy that utilizes light to activate a photosensitizer drug to achieve localized cellular damage, has been explored in recent years. It has been reported that autophagy in PDT is significantly influenced by the treatment protocol. In this work, the role of Photofrin, a well‐established clinical photosensitizer, in regulating cellular autophagy was investigated. The effects of Photofrin on cellular autophagy induced by conventional starvation or rapamycin techniques were studied. By fluorescence imaging, Western blotting and cell viability assays, it was found that Photofrin can effectively inhibit cellular autophagy induced by starvation or rapamycin. This autophagy blocking is independent of the photosensitizing property of the drug. With Baf‐A1, a well‐established agent that inhibits autophagosome from fusing with lysosome, we also found that, the observed phenomenon is not due to accelerated degradation of existing autophagosomes, thus proving that the drug Photofrin alone, without light excitation, can truly block autophagy. J. Cell. Physiol. 224: 414–422, 2010. © 2010 Wiley‐Liss, Inc.
Constitutive activation of the mitogen‐activated protein kinase pathway impairs vitamin D signaling in human prostate epithelial cells
Authors: Zhang Zhentao , Kovalenko Pavlo , Cui Min , DeSmet Marsha , Clinton Steven K. , Fleet James C.
Published: April 2010

We studied the effect of prolonged activation of mitogen‐activated protein kinase (MAPK) signaling on 1,25 dihydroxyvitamin D (1,25(OH)2D3) action in the immortalized human prostate epithelial cell line RWPE1 and its Ki‐Ras transformed clone RWPE2. 1,25(OH)2D3‐treatment caused growth arrest and induced gene expression in both cell lines but the response was blunted in RWPE2 cells. Vitamin D receptor (VDR) levels were lower in RWPE2 cells but VDR over‐expression did not increase vitamin‐D‐mediated gene transcription in either cell line. In contrast, MAPK inhibition restored normal vitamin D transcriptional responses in RWPE2 cells and MAPK activation with constitutively active MEK1R4F reduced vitamin‐D‐regulated transcription in RWPE1 cells. 1,25(OH)2D3‐mediated transcription depends upon the VDR and its heterodimeric partner the retinoid X receptor (RXR) so we studied whether changes in the VDR–RXR transcription complex occur in response to MAPK activation. Mutation of putative phosphorylation sites in the activation function 1 (AF‐1) domain (S32A, T82A) of RXRα restored 1,25(OH)2D3‐mediated transactivation in RWPE2 cells. Mammalian two‐hybrid and co‐immunoprecipitation assays revealed a vitamin‐D‐independent interaction between steroid receptor co‐activator‐1 (SRC‐1) and RXRα that was reduced by MAPK activation and was restored in RWPE2 cells by mutating S32 and T82 in the RXRα AF‐1 domain. Our data show that a common contributor to cancer development, prolonged activation of MAPK signaling, impairs 1,25(OH)2D3‐mediated transcription in prostate epithelial cells. This is due in part to the phosphorylation of critical amino acids in the RXRα AF‐1 domain and impaired co‐activator recruitment. J. Cell. Physiol. 224: 433–442, 2010. © 2010 Wiley‐Liss, Inc.
Signaling pathways implicated in PGF2α effects on Fgf2+/+ and Fgf2−/− osteoblasts
Authors: Sabbieti Maria Giovanna , Agas Dimitrios , Marchetti Luigi , Santoni Giorgio , Amantini Consuelo , Xiao Liping , Menghi Giovanna , Hurley Marja M.
Published: April 2010

Prostaglandin F2α (PGF2α) regulates fibroblast growth factor‐2 (FGF‐2) and fibroblast growth factor receptor (FGFR) expression in osteoblasts. Here, the role of FGF‐2 in PGF2α‐induced proliferation and the signaling pathway involved, were determined in calvarial osteoblasts (COBs) from Fgf2+/+ and Fgf2−/− mice. The involvement of the exported FGF‐2 isoform, was determined using the FGF‐2 neutralizing antibody to alter its binding to FGFR1. PGF2α increased activity of Ras, and MAP‐kinase cascade as well as Bcl‐2 and c‐Myc levels in Fgf2+/+ but not in Fgf2−/− COBs. Moreover, in Fgf2+/+ COBs, PGF2α‐enhanced nuclear accumulation and co‐localization of Bcl‐2/c‐Myc. Although up‐regulation of multiple proliferative and survival signals were induced by PGF2α in Fgf2+/+ COBs, phospho‐p53 was unmodified while p53 was increased. Increased phospho‐p53 was, instead, found in Fgf2−/− COBs without up‐regulation of oncogenic proteins. The lack of p53 activation in wild type osteoblasts could be due in part to the overexpression of MDM2 caused by PGF2α via FGF‐2. PGF2α, also, increased cyclins D and E in Fgf2+/+ COBs and induced an expansion of Fgf2+/+ osteoblasts in G2/M phase. These data clearly show that PGF2α induces proliferation via endogenous FGF‐2 and the exported isoform mediates PGF2α effects by acting in autocrine manner. Furthermore, silencing of FGFR1 in Fgf2+/+ COBs blocked PGF2α induced increase of phospho‐MDM2 and cyclins. J. Cell. Physiol. 224: 465–474, 2010. © 2010 Wiley‐Liss, Inc.
Adiponectin increases BMP‐2 expression in osteoblasts via AdipoR receptor signaling pathway
Authors: Huang Chun‐Yin , Lee Chun‐Yi , Chen Meng‐Yi , Tsai Hsiao‐Chi , Hsu Horng‐Chaung , Tang Chih‐Hsin
Published: April 2010

Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes and involved in energy homeostasis. Bone morphogenetic protein (BMP) plays important roles in osteoblastic differentiation and bone formation. However, the effects of adiponectin on BMPs expression in cultured osteoblasts are largely unknown. Here we found that adiponectin increased mRNA expression of BMP‐2 but not other BMPs in cultured osteoblastic cells. Stimulation of osteoblasts with adiponectin also increased protein levels of BMP‐2 by Western blot and ELISA assay. Adiponectin‐mediated BMP‐2 expression was attenuated by 5′‐AMP‐activated protein kinase (AMPK) small interference RNA and AMPK inhibitor (araA and compound C). Activations of p38 and NF‐κB pathways after adiponectin treatment were demonstrated, and adiponectin‐induced expression of BMP‐2 was inhibited by the specific inhibitor and mutant of p38 and NF‐κB cascades. Taken together, our results provide evidence that adiponectin enhances BMP‐2 expression in osteoblastic cells, and AdipoR1 receptor, AMPK, p38 and NF‐κB signaling pathways may be involved in increasing BMP‐2 expression by adiponectin. J. Cell. Physiol. 224: 475–483, 2010. © 2010 Wiley‐Liss, Inc.
Cell death of prostate cancer cells by specific amino acid restriction depends on alterations of glucose metabolism
Authors: Fu Ya‐Min , Lin Huimin , Liu Xiaoyi , Fang Weigang , Meadows Gary G.
Published: April 2010

Selective amino acid restriction targets mitochondria resulting in DU145 and PC3 prostate cancer cell death. This study shows that restriction of tyrosine and phenylalanine (Tyr/Phe), glutamine (Gln), or methionine (Met) differentially modulates glucose metabolism, glycogen synthase kinase 3β (GSK3β), p53, and pyruvate dehydrogenase (PDH) in these two cell lines. In DU145 cells, Gln and Met restriction increase glucose consumption, but Tyr/Phe restriction does not. Addition of glucose to culture media diminishes cell death induced by Tyr/Phe‐restriction. Addition of pyruvate reduces cell death due to Tyr/Phe and Gln restriction. Tyr/Phe, Gln and Met restriction increase phosphorylation of GSK3β‐Ser9, phosphorylation of p53‐Ser15 and reduce the mitochondrial localization of PDH. Addition of glucose or pyruvate to cultures significantly reverses the alterations in GSK3β, p53 and PDH induced by amino acid restriction. In p53‐null PC3 cells, Tyr/Phe, Gln and Met restriction decreases glucose consumption, reduces phosphorylation of Akt‐Ser473, and increases phosphorylation of GSK3β‐Ser9. Addition of pyruvate or glucose reduces death of Met‐restricted cells. Addition of glucose increases phosphorylation of Akt‐Ser473 in amino acid‐restricted cells reduces phosphorylation of GSK3β‐Ser9 in Tyr/Phe and Gln restricted cells and increases phosphorylation of GSK3β‐Ser9 in Met restricted cells. Addition of pyruvate reduces phosphorylation of GSK3β‐Ser9 in all amino acid‐restricted cells. In summary, cell death induced by specific amino acid restriction is dependent on or closely related to the modulation of glucose metabolism. GSK3β (DU145 and PC3) and p53 (DU145) are crucial switches connecting metabolism and these signaling molecules to cell survival during amino acid restriction. J. Cell. Physiol. 224: 491–500, 2010. © 2010 Wiley‐Liss, Inc.
Interleukin‐1β induces ICAM‐1 expression enhancing leukocyte adhesion in human rheumatoid arthritis synovial fibroblasts: Involvement of ERK, JNK, AP‐1, and NF‐κB
Authors: Yang Chuen‐Mao , Luo Shue‐Fen , Hsieh Hsi‐Lung , Chi Pei‐Ling , Lin Chih‐Chung , Wu Chi‐Chuan , Hsiao Li‐Der
Published: April 2010

Interleukin‐1β (IL‐1β) has been shown to induce the expression of adhesion molecules on various cell types and contributes to inflammatory responses. However, the molecular mechanisms by which IL‐1β induced intercellular adhesion molecule (ICAM)‐1 expression remain unclear in human rheumatoid arthritis synovial fibroblasts (RASFs). Here, we demonstrated that IL‐1β induces ICAM‐1 gene expression via the de novo protein synthesis through transcription and translation, which is attenuated by pretreatment with actinomycin D and cycloheximide, respectively. IL‐1β‐induced ICAM‐1 expression, extracellular signal‐regulated kinase (ERK) and c‐Jun‐N‐terminal kinase (JNK) phosphorylation, AP‐1 activation, and nuclear factor‐κB (NF‐κB) p65 translocation were attenuated by the inhibitors of MEK1/2 (U0126), JNK (SP600125), AP‐1 (tanshinone IIA), and NF‐κB (helenalin) or transfection with respective short hairpin RNA plasmids. Moreover, IL‐1β‐stimulated NF‐κB p65 translocation was blocked by helenalin, but not by U0126 or SP600125, revealing that MAPKs and NF‐κB pathways were independent on these responses. IL‐1β‐stimulated AP‐1 activation was blocked by U0126 or SP600125, revealing that ERK and JNK linked to AP‐1 on these responses. IL‐1β‐stimulated ICAM‐1 gene expression was attenuated by pretreatment with U0126, SP600125, tanshinone IIA, or helenalin, revealed by ICAM‐1 promoter assay and real‐time RT‐PCR analysis. Finally, up‐regulation of ICAM‐1 enhanced the adhesion of leukocytes to RASFs exposed to IL‐1β. These results suggest that in human RASFs, activation of ERK, JNK, AP‐1, and NF‐κB are essential for IL‐1β‐induced ICAM‐1 expression and leukocyte adhesion. J. Cell. Physiol. 224: 516–526, 2010. © 2010 Wiley‐Liss, Inc.
Protection capabilities of nanostructured shells toward cell encapsulation: A saccharomyces/paramecium model
Authors: Magrassi Raffaella , Ramoino Paola , Bianchini Paolo , Diaspro Alberto
Published: April 2010

In this work we report the formation of nanostructured hybrid objects, made up of living cells encapsulated in a protective multilayer shell assembly of nanostructured polyelectrolyte. Such constructs can be hosted on nanostructured surfaces or can be installed around living organisms, at the right time. Their construction is based on the layer‐by‐layer (LbL) self‐assembly of two oppositely alternated charged polyelectrolytes (PEs) on cell membranes as earlier done for nanocapsules or fuzzy structured nanoshells. This communication reports the optimal conditions for cell encapsulation in terms of nanoshell design and construction. Microsc. Res. Tech. 73:931–936, 2010. © 2010 Wiley‐Liss, Inc.
Dynamics of nucleic acid/cationic polymer complexation and disassembly under biologically simulated conditions using in situ atomic force microscopy
Authors: Shim Min Suk , Wang Xi , Ragan Regina , Kwon Young Jik
Published: April 2010

Elucidating dynamic morphological changes of gene‐carrying vectors and their nucleic acid release under varying intracellular conditions has been a technical challenge. Atomic force microscopy (AFM) was used to observe nucleic acid/polymer polyplexes under endosomal and reducible cytosolic conditions. Both ketalized (acid‐degradable) and unmodified (nondegradable) polyethylenimine (PEI) in linear and branched forms were used to prepare plasmid DNA‐ or siRNA‐complexing polyplexes. Then, the polyplexes' complexation and disassembly were observed by in situ AFM in various differentially changing buffers that represent intracellular conditions. Results demonstrated obvious morphological destruction of DNA/ketalized linear PEI (KL‐PEI) polyplexes under mildly acidic endosomal conditions, whereas no morphological changes were observed by DNA/ketalized branched PEI (KB‐PEI) under the same conditions. In addition, siRNA was more efficiently dissociated from KL‐PEI than KB‐PEI under the same conditions. Nondegradable PEI did not show any evidence that DNA or siRNA was released. Anionic biomacromolecules (e.g., heparan sulfate), which was hypothesized to dissociate nucleic acids from cationic polymers, did not successfully disassemble polyplexes but appeared to be adsorbed on cationic polymers. The in situ AFM results combined with in vitro cellular transfection and gene silencing indicated that efficient endosomal escape of plasmid DNA in a compact polyplex form is required for efficient gene expression. On the contrary, rapid dissociation of siRNA from its cationic carrier is crucial for efficient gene silencing. The findings of this study may provide new insightful information for designing stimuli‐responsive nonviral gene vectors as well as expanding tools for investigating nonviral vectors in nanoscales under biologically inspired conditions. Microsc. Res. Tech. 73:845–856, 2010. © 2010 Wiley‐Liss, Inc.
Elemental composition of Physarum compressum Alb. et Schw. sporocarps and their structures cultivated on rabbit dung and agar substrates
Authors: Janik Paulina , Tylko Grzegorz , Ostachowicz Beata , Turnau Katarzyna
Published: April 2010

The elemental composition of spores, peridium walls, and lime nodes of Physarum compressum sporocarps, cultivated on rabbit dung as a natural growing environment for the slime mold and on artificial agar medium, was compared to evaluate differences that may be dependent on substrates. Whole fruiting bodies and samples of both experimental media were extracted with nitric acid or Parr digest bomb, respectively, and analyzed by means of total X‐ray reflection fluorescence (TXRF). Electron probe microanalysis (EPMA) of spores, peridium walls, and lime nodes structure was carried out with the scanning electron microscope equipped with energy‐dispersive spectrometer. Because of minute sizes and roughness of investigated structures, Monte Carlo simulations were utilized to establish analytical conditions of EPMA. Biological and geological standards were used in the quantification of element concentrations. According to TXRF, the fruiting bodies from agar medium revealed lower concentrations of K, Ca, Cr, Mn, and Fe in relation to fruiting bodies from the dung, reflecting elemental relationships in the experimental media. According to EPMA, the highest Ca concentration was found in the lime nodes followed by the peridium and the spores. Culturing of the slime molds on the rabbit dung indicated higher concentration of Ca in the lime nodes and peridium walls when compared with those obtained from the sporocarps grown on agar media. The opposite relation was found for the spores. The concentration of Na, Mg, P, S, and Cl was generally lower in all structures of the sporocarps harvested from the dung than from the agar medium. K was in higher concentration in analyzed structures from dung than from agar. Different element uptake (except for Ca and K) was revealed by the two methods: TXRF and EPMA. Microsc. Res. Tech. 73:1134–1142, 2010. © 2010 Wiley‐Liss, Inc.
2‐Butyl‐5‐chloro‐3H‐imidazole‐4‐carbaldehyde as a new synthon for the synthesis of fused ring heterocycles via intramolecular 1,3‐dipolar cycloaddition reactions
Authors: Gaonkar S. L. , Lokanatha Rai K. M.
Published: April 2010

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The title compound 2‐butyl‐5‐chloro‐3H‐imidazole‐4‐carbaldehyde was transformed into tricyclic heterocycles by substituting the chlorine atom by an unsaturated thiolate or alkoxide and then converting aldehyde function into 1,3‐dipole. Chloramine‐T was used as an efficient reagent for the generation of 1,3‐dipoles, which resulted the formation of fused ring heterocycles via intramolecular 1,3‐dipolar cycloaddition reaction. The method is very useful for the construction of many biologically active fused heterocycles. J. Heterocyclic Chem., (2010).
Synthesis of some new pyridones, fused pyrimidines, and fused 1,2,4‐triazines
Authors: Mohamed Mahmoud A.
Published: April 2010

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Cyclocondensation of hydrazides, 3‐aminopyrazoles, 3‐amino‐1,2,4‐triazole, 2‐aminobenzoimidazole, pyrazole‐3‐diazonium salts, 1,2,4‐triazol‐3‐diazonium salt, or benzoimidazole‐2‐diazonium salt with sodium salt of 3‐hydroxy‐1‐(2‐naphthyl)prop‐2‐en‐1‐one gave 2‐pyridones, pyrazolo[1,5‐a]pyrimidines, triazolo[1,5‐a]pyrimidine, benzo[4,5]imidazo[1,2‐a]pyrimidine, (pyrazolo[5,1‐c][1,2,4]triazin‐3‐yl)‐methanone, [1,2,4]triazolo[5,1‐c][1,2,4]triazin‐3‐yl‐methanone, or benzo[4,5]imidazo[2,1‐c] [1,2,4]triazin‐3‐yl‐methanone derivatives, respectively, which will be tested for anti‐tumor and anti‐cancer activates. J. Heterocyclic Chem., (2010).
Synthesis of imidazo[1,2‐c]quinazolin‐5(6H)‐ones and benzimidazo[1,2‐c]quinazolin‐6(5H)‐ones with the aid of low‐valent titanium reagent
Authors: Zhao Xuan , Shi Da‐Qing
Published: April 2010

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A short and facile synthesis of imidazo[1,2‐c]quinazolin‐5(6H)‐ones and benzimidazo[1,2‐c]quinazolin‐6(5H)‐ones was accomplished in good yields via the novel reductive cyclization of 2‐(2‐nitrophenyl)imidazoles or 2‐(2‐nitrophenyl)benzoimidazoles with isocyanates promoted by low‐valent titanium reagent. J. Heterocyclic Chem., (2010).
The reaction of 2‐dimethylaminomethylene‐3‐oxo‐N‐phenylbutyramide with active methylene nitriles
Authors: Abdelrazek Fathy M. , Sharaf Mohey F. , Metz Peter , Jaeger Anna
Published: April 2010

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2‐Dimethylaminomethylene‐3‐oxo‐N‐phenylbutyramide 1 reacts with malononitrile 2a to afford the pent‐2‐enedioic acid 1‐amide 5‐phenylamide derivative 6, which could be cyclized to give the 6‐methylpyridone derivative 7. Compound 1 reacts with cyanoacetamide 2b to afford the same pyridone 7 and with cyanothioacetamide 2c to afford the analogous pyridinethione 12. Compound 12 reacts with DMAD to afford the pyridine derivative 15 and with N,N‐dimethylchloroacetamide 16 to afford the thieno[2,3‐d]pyridine derivative 18. Compound 18 reacts with morpholine‐4‐carboxaldehyde 19, N,N‐diemthylformamide 20, and 2,5‐dimethoxy‐tetrahydrofuran 21 to afford the fully aromatic thieno[2,3‐d]pyridine derivatives 22, 23, and 24, respectively. J. Heterocyclic Chem., (2010).
Synthesis of some new pyridazin‐3‐one derivatives and their utility in heterocyclic synthesis
Authors: El‐Mobayed Medhat M. , Hussein Ahmed M. , Mohlhel Wafia M.
Published: April 2010

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Synthesis of new heterocyclic compounds containing the pyridazinone moiety, which have a valuable biological activities, has been achieved through the nucleophilic addition of benzylamine to 4‐(p‐substituted phenyl)‐4‐oxo‐2‐butenoic acid 1a, 1b, followed by cyclocondensation of the adducts 2a, 2b to the corresponding pyridazin‐3‐one derivatives 3a, 3b. The behavior of the latter compounds toward different nucleophilic and electrophilic reagents was investigated. The structures of the newly synthesized compounds were elucidated by elemental analysis and spectroscopic data. J. Heterocyclic Chem., (2010).
Synthesis, antioxidant and antimicrobial activity of novel benzene‐1,4‐diamine‐bis‐dioxaphosphepine‐6λ5 iminophosphoranes
Authors: Narayana Reddy M. Veera , Sekhar Reddy G. Chandra , Kumar K. Suresh , Reddy C. Suresh , Raju C. Naga
Published: April 2010

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A new class of novel benzene‐1,4‐diamine‐bis‐dioxaphosphepine‐6λ5 iminophosphoranes (5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j) were synthesized by the reaction of 6‐chlorodibenzo[d,f][1,3,2]dioxaphosphepine (2) with 1,4‐diaminobenzene to form bis‐dibenzo[d,f][1,3,2]dioxaphosphepin‐6‐yl‐benzene‐diamine (3). Its subsequent reaction with different alkyl/aryl azides (4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j) in tetrahydrofuran at 50–60°C under inert atmosphere yielded title compounds. Their structures were established by elemental analysis, IR, 1H, 13C, 31P NMR, and mass spectral studies. All the title compounds were screened for antioxidant properties and found to exhibit potent in vitro antioxidant and antimicrobial activity J. Heterocyclic Chem., (2010).
Pediatric oncologists' attitudes towards involving adolescents in decision‐making concerning research participation
Authors: de Vries Martine C. , Wit Jan M. , Engberts Dirk P. , Kaspers Gertjan J.L. , van Leeuwen Evert
Published: April 2010

Background

Various regulations and guidelines stipulate the importance of involving adolescents in decision‐making concerning research participation. Several studies have shown that in the context of pediatric oncology this involvement is difficult to achieve due to emotional stress, the complexity of research protocols and limited time. Still, up to 80% of adolescents with cancer enter onto a trial during their illness. The aim of this study was to determine clinicians' views and attitudes towards enrolling adolescents in research, considering the difficulties surrounding their involvement in decision‐making.

Methods

A qualitative multicenter study was performed, using in‐depth semi‐structured interviews on the informed consent process with 15 pediatric hemato‐oncologists.

Results

Four central themes emerged that characterize clinicians' attitudes towards involving adolescents in the decision‐making process: (1) clinicians regard most adolescents as not capable of participating meaningfully in discussions regarding research; (2) clinicians do not always provide adolescents with all information; (3) proxy consent from parents is obtained and is deemed sufficient; (4) clinician‐investigator integrity: clinicians judge research protocols as not being harmful and even in the best interest of the adolescent.

Conclusions

Clinicians justify not involving adolescents in research discussions by referring to best interest arguments (adolescents' incompetence, proxy consent, and investigator integrity), although this is not in line with legal regulations and ethical guidelines. Pediatr Blood Cancer 2010;55:123–128. © 2010 Wiley‐Liss, Inc.
The use of high resolution computerized tomography (HRCT) of the chest in evaluating the effect of tobramycin solution for inhalation in cystic fibrosis lung disease
Authors: Nasr Samya Z. , Sakmar Ermelinda , Christodoulou Emmanuel , Eckhardt Boris P. , Streetman Daniel S. , Strouse Peter J.
Published: April 2010

Objectives

To compare the usefulness of HRCT of the chest versus spirometric measures (PFTs) in evaluating the effect of tobramycin solution for inhalation (TSI) in cystic fibrosis (CF).

Methods

Thirty‐two CF patients with mostly mild lung disease age ≥6 years, were enrolled in a double‐blind, placebo‐controlled pilot study. Patients were chronically colonized with Pseudomonas aeruginosa for at least 6 months prior to and at enrollment. If patients were on TSI, they were taken off for at least 3 months prior to enrollment. Duration was 6 months; 31 subjects completed the study. HRCT and PFTs were evaluated at baseline, after 28 days of treatment and at the end of the study. Study medication was administered as 5 ml nebulized treatment twice a day for 28 days followed by 28 days off (one cycle). Study consisted of three cycles. Two radiologists scored all films using a validated system. A total HRCT score consists of the sum of subscores: linear opacities, hyperinflation, nodular opacities, peribronchial thickening, mucous plugging, and bronchiectasis; each subscore could range from 0 to 80, with potential total scores varying from 0 to 480. The percent of the maximum possible HRCT score was then calculated and used for all comparisons.

Results

Using two tailed paired t‐test, the percent maximum HRCT score decreased by 1.4 ± 2.6% (mean ± SD) (P = 0.049) and 0.3 ± 2.8% (P = 0.63) for the TSI group and decreased by 0.1 ± 1.5% (P = 0.74) and increased by 0.6 ± 1.8% (P = 0.23) for the placebo group between visits 1 and 2, and visits 1 and 3, respectively. The data were then analyzed using a mixed model utilizing changes in scores over the durations of the study for each group. The change of HRCT score for the TSI group was −0.24/day (P = 0.02) and −0.03/day (P = 0.22), and for the control group the change was −0.01 (P = 0.93) and 0.02 (P = 0.29) between visits 1 and 2, and visits 1 and 3 respectively. FEF25–75% and FEV1% changes were not statistically significant using both analyses.

Conclusion

HRCT seems to be more sensitive in detecting treatment effect than PFT in CF patients with mild lung disease, especially following the first treatment period (visit 2). Total HRCT score showed some improvement at the end of the study, though not statistically significant. This is probably due to obtaining the HRCT an average of 30 days after completion of the TSI treatment, and selection of study population with mostly mild lung disease. This could indicate that the most significant improvement in the total HRCT score in this patient population occurs after the first treatment period with TSI. Pediatr Pulmonol. 2010; 45:440–449. © 2010 Wiley‐Liss, Inc.
Sleep‐disordered breathing in children with thoracic insufficiency syndrome
Authors: Striegl Amanda , Chen Maida L. , Kifle Yemiserach , Song Kit , Redding Gregory
Published: April 2010

Thoracic insufficiency syndrome (TIS) is a collection of chest and spine malformations that results in progressively restrictive pulmonary mechanics and an inability of the thorax to adequately support lung growth. Many children with TIS are too young to perform standard pulmonary function tests, yet need functional assessments of their restrictive thoracic disease. We report on the sleep architecture and frequency of sleep‐related breathing abnormalities in 11 children with TIS who underwent overnight polysomnography from retrospective chart review. Ten of 11 (92%) had sleep disordered breathing as defined by currently accepted criteria of apnea–hypopnea index (AHI) >2 events/hr. The median AHI was 4.3 events/hr, with obstructive hypopneas (median 3.7 events/hr) accounting for 75% of abnormalities. Respiratory events occurred most frequently during REM sleep (median REM‐AHI 17.3 events/hr), and were associated with oxyhemoglobin desaturation, and rarely carbon dioxide retention. Sleep disordered breathing with hypoxemia appears to be a common but under recognized problem among children with TIS. Polysomnogram may have a role as a non‐invasive screening tool used in conjunction with other functional respiratory assessments in children with TIS, and warrants further study in a prospective manner. Pediatr Pulmonol. 2010; 45:469–474. © 2010 Wiley‐Liss, Inc.
Management of children with empyema: Pleural drainage is not always necessary
Authors: Carter Edward , Waldhausen John , Zhang Weiya , Hoffman Lucas , Redding Gregory
Published: April 2010

Background

There is considerable variation in the management of pediatric empyema, and there are no clear criteria for when to perform pleural drainage. Our study aims were: (1) to retrospectively review our experience with an empyema treatment strategy that started with intravenously administered (IV) antibiotics alone in medically stable patients with procession to pleural drainage only if there was no clinical improvement after 48 hr, and (2) to identify predictors for undergoing pleural drainage.

Methods

We performed a retrospective review of 182 previously healthy children, 1–18 years old, hospitalized with empyema from December 1996 through December 2008. The primary outcome measures were the proportion of patients requiring pleural drainage procedures and hospital length of stay (LOS).

Results

Ninety‐five children (52%) received antibiotics alone, and 87 (45%) underwent drainage procedures (21 chest tube alone, 57 VATS/thoracotomy, and 8 chest tube followed by VATS/thoracotomy); only 4 received fibrinolytics. Mean (standard deviation) LOS was significantly shorter in the antibiotics alone group, 7.0 (3.5) versus 11 (4.0) days. The strongest predictors of undergoing pleural drainage were admission to the intensive care unit and large effusion size (>½ thorax filled).

Conclusions

Some children with empyema can be treated with IV antibiotics alone and have reasonably short LOS. At our institution, those that required intensive care or had large effusions with mediastinal shift were more likely to require pleural drainage. Pediatr Pulmonol. 2010; 45:475–480. © 2010 Wiley‐Liss, Inc.
Analyzing language demands facing english learners on science performance assessments: The sald framework
Authors: Shaw Jerome M. , Bunch George C. , Geaney Edward R.
Published: April 2010

This article report on the development and use of an analytical framework intended to map the language demands encountered by English learners as they engage in science performance assessments. Grounded in functional and interactional views of language and language use, the authors—two science education researchers and a language scholar—developed the framework via an inductive, iterative, and systematic review of written assessment materials associated with three fifth grade science performance tasks. The resulting Science Assessment Language Demands (SALD) framework is organized around three dimensions: participant structures, communicative modes, and written texts and genres that students are called upon to read and produce. The authors used textual analysis to conduct an expert review of the written documents associated with the three assessment tasks. The results indicate that the framework can be used to document a wide range of functional and interactional language demands involved in science performance assessments. The demands revealed by the SALD framework highlight both potential challenges facing English learners during science performance assessments as well as opportunities afforded by such assessments for demonstrating their knowledge and skills and further developing language proficiency. A major implication of the study is the potential use of the framework to evaluate the language demands and opportunities of science assessments used in classrooms with English learners. © 2010 Wiley Periodicals, Inc. J Res Sci Teach 47: 909–928, 2010
Construction grammar
Authors: Goldberg Adele , Suttle Laura
Published: April 2010

Construction grammar, or constructionist approaches more generally, emphasize the function of particular constructions as well as their formal properties. Constructions vary in their degree of generality, from words to idioms to more abstract patterns such as argument structure constructions, topicalization, and passive. There is also no division drawn between semantics and pragmatics, as all conventional aspects of constructions are encoded within the constructions themselves; thus constructions can include information about information structure, register, or genre. The majority of constructionist approaches are also usage based, in that they recognize that we retain a great deal of item‐specific information. An important desideratum of constructionist approaches is that they interface naturally with what we know about language acquisition, language change, and language typology. In order to capture generalizations within a given language, constructions are related via an inheritance hierarchy, with more abstract, productive constructions being directly related to their more idiomatic instantiations. The functions of particular constructions as well as domain general cognitive and social cognition are appealed in order to capture cross‐linguistically valid typological generalizations. Copyright © 2010 John Wiley & Sons, Ltd.

This article is categorized under:

Linguistics > Linguistic Theory
The acquisition of semantics
Authors: Wagner Laura
Published: April 2010

This review piece looks at how children acquire various elements of linguistic meaning. It considers issues in the acquisition of word meaning, argument structure, tense and aspect, and quantification and scope. For each of these areas, it considers the problems they pose for the acquisition process in general, reviews basic findings from the field of acquisition, and identifies outstanding questions in the field. Copyright © 2010 John Wiley & Sons, Ltd.

This article is categorized under:

Linguistics > Language Acquisition
Desire: philosophical issues
Authors: Schroeder Timothy
Published: April 2010

To desire something is to want it, wish it, long for it. Various leading theories of this attitude exist, with the most prominent theory holding that to desire something is nothing more than to be inclined to take actions that will obtain that thing. Other important theories tie desires to pleasure and displeasure, to reasons and goodness, or to reward learning. All of these theories leave room for scientific investigation of what causes us to desire, and of what else desires might cause in us. Philosophical speculation on these topics has focused, in the former case, on the generation of new desires from existing desires. In the latter case, it has roamed across topics diverse as the influence of desire on cognition, the relation of desire to mental disorder, and causation of self‐knowledge of one's own desires. Copyright © 2010 John Wiley & Sons, Ltd.

This article is categorized under:

Philosophy > Action

Philosophy > Foundations of Cognitive Science
Language acquisition and language change
Authors: Lightfoot David
Published: April 2010

Children acquire a mature language system and sometimes this system differs from that of their parents. This is a significant part of language change and understanding acquisition is key to understanding this kind of change in people's internal grammars. I outline one approach to language acquisition, based on children finding cues expressed in the input they are exposed to. This enables us to understand historical change in grammars: change in external language sometimes triggers a new internal grammar as cues come to be expressed differently. Work on language variation, acquisition, and change converges, and these three areas are mutually dependent; empirical work in one area may enrich understanding more generally, opening the way to new kinds of empirical work. Seen this way, language is a complex system and language change can be treated productively in the context of complexity science. Copyright © 2010 John Wiley & Sons, Ltd.

This article is categorized under:

Linguistics > Language Acquisition
Model‐based approaches to neuroimaging: combining reinforcement learning theory with fMRI data
Authors: Gläscher Jan P. , O'Doherty John P.
Published: April 2010

The combination of functional magnetic resonance imaging (fMRI) with computational models for a given cognitive process provides a powerful framework for testing hypotheses about the neural computations underlying such processes in the brain. Here, we outline the steps involved in implementing this approach with reference to the application of reinforcement learning (RL) models that can account for human choice behavior during value‐based decision making. The model generates internal variables which can be used to construct fMRI predictor variables and regressed against individual subjects' fMRI data. The resulting regression coefficients reflect the strength of the correlation with blood oxygenation level dependent (BOLD) activity and the relevant internal variables from the model. In the second part of this review, we describe human neuroimaging studies that have employed this analysis strategy to identify brain regions involved in the computations mediating reward‐related decision making. Copyright © 2010 John Wiley & Sons, Ltd.

This article is categorized under:

Neuroscience > Cognition
Analyzing effective connectivity with functional magnetic resonance imaging
Authors: Stephan Klaas Enno , Friston Karl J.
Published: April 2010

Functional neuroimaging techniques are used widely in cognitive neuroscience to investigate aspects of functional specialization and functional integration in the human brain. Functional integration can be characterized in two ways, functional connectivity and effective connectivity. While functional connectivity describes statistical dependencies between data, effective connectivity rests on a mechanistic model of the causal effects that generated the data. This review addresses the conceptual and methodological basis of established techniques for characterizing effective connectivity using functional magnetic resonance imaging (fMRI) data. In particular, we focus on dynamic causal modeling (DCM) of fMRI data and emphasize the importance of model selection procedures and nonlinear mechanisms for context‐dependent changes in connection strengths. Copyright © 2010 John Wiley & Sons, Ltd.

This article is categorized under:

Neuroscience > Cognition
Genetic differentiation between sun and shade habitats in populations of Lindera benzoin L.
Authors: Mooney Emily , Edwards Marten , Niesenbaum Richard
Published: April 2010

Differences in selection patterns among habitats can alter the distribution of genetic diversity even when this is estimated with neutral markers. For plants, light is an essential resource that can influence both abiotic and biotic components of habitat. We examined genetic differentiation between sun and shade habitats in Lindera benzoin L. (Spicebush), a perennial understory shrub. Genetic diversity of 127 plants from sun and shade habitats in two populations of L. benzoin was determined using 12 polymorphic microsatellite markers. We analyzed patterns of genetic diversity using analysis of molecular variance (AMOVA), and we assessed correlation between genetic and geographic distance using Mantel tests. We found (1) low levels of differentiation among populations (FST = 0.028), (2) little evidence of genetic structure within populations due to isolation‐by‐distance, and (3) some evidence of habitat‐based genetic differentiation. Specifically, the AMOVA showed a small (0.5%) but significant portion of overall variation could be explained by differences between habitats. The overall low levels of differentiation we saw were likely a result of extensive gene flow in this dioecious, bird‐dispersed species.
Preparation and Surface Activity of Phosphated Alkyl Oligoglucosides
Authors: Chen Keng‐Ming , Lin Li‐Huei , Dong Min‐Yan , Wang Chien Fu , Hwang Mou‐Chuan
Published: April 2010

A family of phosphated alkyl oligoglucoside surfactants was prepared by reacting alkyl oligoglucosides with phosphorus oxychloride. The alkyl oligoglucosides were obtained by an usual method in which the glucose is reacted with a fatty alcohol containing 10–18 carbon atoms. These novel phosphated surfactants have been found to exhibit good surface tension, foaming and wetting power. The critical micelle concentration was found to increase with the length of hydrocarbon chain of the surfactant. The surface excess concentration and the interfacial area per surfactant molecule are reported. These phosphated surfactants also exhibit a good performance to improve the whiteness and wetting of cotton fabrics in a hydrogen oxide bleaching system, and they are also found to be more biodegradable than conventional surfactants.