bluuebunny/crossref_metadata_2025 huggingface dataset:
β8 integrin and band 4.1B cooperatively regulate morphogenesis of the embryonic heart
Authors: Jung Youngsin , Kissil Joseph L. , McCarty Joseph H.
Published: December 2010

Morphogenesis of the heart is regulated by various cues, including growth factors and extracellular matrix (ECM) proteins. The mechanisms by which cardiac cells properly integrate these cues to regulate growth, differentiation, and migration remain poorly understood. Here we have used genetic strategies in mice to identify αvβ8 integrin and its cytoskeletal adaptor protein, Band 4.1B, as essential regulators of cardiac morphogenesis. We demonstrate that approximately 60% of mouse embryos genetically null for β8 integrin and Band 4.1B display cardiovascular phenotypes and die by E11.5. This premature death is due, in part, to defective development of the cardiac outflow tract (OFT), with reduced expression of smooth muscle α‐actin (SMAα‐actin) in OFT cells derived from the cardiac neural crest. These data are the first to identify cell adhesion and signaling pathways regulated by αvβ8 integrin and Band 4.1B as essential for normal formation and function of the heart during embryogenesis. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.
The dynamic gene expression patterns of transcription factors constituting the sea urchin aboral ectoderm gene regulatory network
Authors: Chen Jen‐Hao , Luo Yi‐Jyun , Su Yi‐Hsien
Published: December 2010

The temporal and spatial expression patterns of regulatory genes are required for building a gene regulatory network (GRN). The current ectoderm GRN model for the sea urchin embryo includes pregastrular specification functions in the oral (OE) and aboral ectoderm (AE). Unlike the OE, which is resolved into several subdomains, the AE is considered a simpler territory due to the lack of detailed gene expression studies in this territory. Here, we perform temporal and spatial gene expression studies on the eight transcription factor genes constituting the AE GRN. Based on the differential gene expression patterns, we conclude that the AE contains at least three subdomains at the mesenchyme blastula stage. We also performed immunostaining for pSmad1/5/8 to monitor the activation of the BMP signaling pathway. The dynamic changes in the expression patterns of these transcription factor genes and the nuclearization of pSmad1/5/8 may provide a foundation for resolving the AE GRN. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.
Identification and expression patterns of members of the protease‐activated receptor (par) gene family during zebrafish development
Authors: Xu Hui , Echemendia Nicholas , Chen Songhai , Lin Fang
Published: December 2010

Protease‐activated receptors (PARs) play critical roles in hemostasis in vertebrates including zebrafish. However, the zebrafish gene classification appears to be complex, and the expression patterns ofpargenes are not established. Based on analyses of genomic organization, phylogenetics, protein primary structure, and protein internalization, we report the identification of four zebrafish PARs:par1,par2a,par2b, andpar3. This classification differs from one reported previously. We also show that these genes have distinct spatiotemporal expression profiles in embryos and larvae, withpar1,par2a, andpar2bexpressed maternally and ubiquitously during gastrula stages and their expression patterns refined at later stages, andpar3expressed only in 3‐day‐old larvae. Notably, the expression patterns of zebrafishpar1andpar2bresemble those of their mammalian counterparts, suggesting that receptor function is conserved among vertebrates. This conservation is supported by our findings that Par1 and Par2b are internalized following exposure to thrombin and trypsin, respectively. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.
FilaminB is required for the directed localization of cell–cell adhesion molecules in embryonic epithelial development
Authors: Wakamatsu Yoshio , Sakai Daisuke , Suzuki Takashi , Osumi Noriko
Published: December 2010

Filamin proteins cross‐link F‐actin and form a scaffold for numerous signal transduction systems. In this study, we show that filaminB is apically enriched in avian embryonic epithelium, and colocalizes with cell adhesion molecules and circumferential F‐actin. FilaminB knockdown in the neural tube and somites decreases the accumulation of N‐cadherin and ZO‐1 protein at cell junctions, and promotes disruption of these tissues and the presence of neuronal aggregates within the lumen of the neural tube. This phenotype resembles that of human congenital condition, periventricular heterotopia (PH). FilaminB knockdown in MDCK cells suggests that filaminB is required for the apical accumulation of adhesion molecules in the junctional complex and subsequent epithelium formation. We further suggest that the reduction of structural integrity of the neural epithelium caused by the loss of Filamin function may also result in formation of the neuronal nodules found in PH patients. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.
A chemical enterocolitis model in zebrafish larvae that is dependent on microbiota and responsive to pharmacological agents
Authors: Oehlers Stefan H. , Flores Maria Vega , Okuda Kazuhide S. , Hall Chris J. , Crosier Kathryn E. , Crosier Philip S.
Published: December 2010

Inflammatory bowel disease (IBD) results from dysfunctional interactions between the intestinal immune system and microbiota, influenced by host genetic susceptibility. Because a key feature of the pathology is intestinal epithelial damage, potential disease factors have been traditionally analyzed within the background of chemical colitis models in mice. The zebrafish has greatly complemented the mouse for modeling aspects of disease processes, with an advantage for high content drug screens. Larval zebrafish exposed to the haptenizing agent trinitrobenzene sulfonic acid (TNBS) displayed impaired intestinal homeostasis and inflammation reminiscent of human IBD. There was a marked induction of pro‐inflammatory cytokines, the degradative enzyme mmp9 and leukocytosis. Enterocolitis was dependent on microbiota and Toll‐like receptor signaling, that can be ameliorated by antibiotic and anti‐inflammatory drug treatments. This system will be useful to rapidly interrogate in vivo the biological significance of the IBD candidate genes so far identified and to carry out pharmacological modifier screens. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.
Embryonic development of the emu, Dromaius novaehollandiae
Authors: Nagai Hiroki , Mak Siu‐Shan , Weng Wei , Nakaya Yukiko , Ladher Raj , Sheng Guojun
Published: December 2010

The chick, Gallus gallus, is the traditional model in avian developmental studies. Data on other bird species are scarce. Here, we present a comparative study of the embryonic development of the chick and the emu Dromaius novaehollandiae, a member of Paleognathae, which also includes the ostrich, rhea, tinamou, kiwi, and cassowary. Emu embryos ranging from Hamburger and Hamilton (HH) equivalent stages 1 to 43 were collected and their gross morphology analyzed. Its early development was studied in detail with time‐lapse imaging and molecular techniques. Emu embryos in general take 2–3 times longer incubation time to reach equivalent chicken stages, requiring 1 day for HH2, 2.5 days for HH4, 7 days for limb bud initiation, 23 days for feather germ appearance, and approximately 50–56 days for hatching. Chordin gene expression is similar in emu and chick embryos, and emu Brachyury is not expressed until HH3. Circulation is established at approximately the 27‐ to 30‐somite stage. Forelimb buds are formed and patterned initially, but their growth is severely retarded. The size difference between an emu and a chick embryo only becomes apparent after limb bud formation. Overall, emu and chick embryogenesis proceeds through similar stages, but developmental heterochrony between these two species is widely observed. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.
Beyond the Closed Suture in Apert Syndrome Mouse Models: Evidence of Primary Effects of FGFR2 Signaling on Facial Shape at Birth
Authors: Martínez‐Abadías Neus , Percival Christopher , Aldridge Kristina , Hill Cheryl A. , Ryan Timothy , Sirivunnabood Satama , Wang Yingli , Jabs Ethylin Wang , Richtsmeier Joan T.
Published: December 2010

Superimposed 3D visualization of the skull and head of mutant and non‐mutant littermates of the FGFR2 P253R mouse model at birth (P0). Lateral views of skeletal bone reconstructed from μCT isosurfaces are displayed. Skin surfaces are visualized from volume renderings; red (top left): Fgfr2+/+ non‐mutant littermate of the P253R model; and green (bottom right): Fgfr2+/P253R mutant littermate. From Martínez‐Abadías et al., Developmental Dynamics 239:3058–3071, 2010.
Solvothermal Synthesis, Characterization, and Formation Mechanism of a Single‐Layer Anatase TiO2 Nanosheet with a Porous Structure
Authors: Chen Yajie , Tian Guohui , Ren Zhiyu , Tian Chungui , Pan Kai , Zhou Wei , Fu Honggang
Published: December 2010

A novel single‐layer polycrystalline anatase TiO2 (SLP TiO2) nanosheet with porous structure was synthesized through a simple solvothermal method by employing rod‐like titanyl sulfate as the starting material in the presence of glycerol, followed by calcination. SEM, TEM, X‐ray diffraction, FTIR spectroscopy, thermogravimetry coupled to FTIR spectroscopy, solid‐state 13C NMR spectroscopy, and N2 adsorption/desorption processes were employed to investigate the structure of the products. The structure and morphology were found to be dependent on the experimental conditions, such as solvothermal reaction time, morphology of titanyl sulfate, and solvent type. The obtained SLP TiO2 nanosheet was employed as a support for loading well‐dispersed Ag nanoparticles and proved to be a good surface‐enhanced Raman scattering (SERS) substrate for the detection of 4‐aminothiophenol and Rhodamine 6G, showing great potential as a convenient and powerful substrate for SERS studies in the field of detecting different target molecules due to good uniformity and reliability.
New Access to and Reactions of P‐Functional Acylphosphane Complexes
Authors: Nesterov Vitaly , Duan Lili , Schnakenburg Gregor , Streubel Rainer
Published: December 2010

P‐Functional (acylphosphane)tungsten complexes 4a–f have been prepared in good yields by the reaction of phosphinidenoid complexes 2a–d with acyl chlorides 3a,b. The reactions of acyl(chloro)phosphane complex 4a at –80 °C with organolithium reagents selectively led to the formation of lithiated phospha‐enolate complex 5b. The ambident reactivity of this compound was demonstrated in reactions with electrophiles such as PhC(O)Cl, MeI, and Me3SiCl, which yielded O‐substituted complexes 6a,b and 8a,b and P‐substituted complex 7.
Synthesis and Characterization of Highly Soluble Two‐Photon‐Absorbing Chromophores with Multi‐Branched and Dendritic Architectures
Authors: Lin Tzu‐Chau , Lin Wei‐Lun , Wang Chih‐Ming , Fu Chih‐Wei
Published: December 2010

A set of novel multi‐polar compounds composed of four fluorene‐based derivatives with systematic alteration of the molecular structure was synthesized and their nonlinear optical properties in the femtosecond and nanosecond time domain were examined. Preliminary experimental results show that the two‐photon activities of the model compounds are connected to structural parameters, such as the number of peripheral electron‐donating groups and/or the size of the π‐domain in a dye molecule. It is also found that these model chromophores possess large nonlinear attenuation under the irradiation of laser pulses working at nanosecond regimes, indicating that these compounds may have strong two‐photon‐assisted excited‐state absorption within the studied spectral region. Effective optical‐power‐limiting behaviors of the dendritic fluorophores were also demonstrated to show that such dye molecules can be potential materials for use as broadband and rapid‐responsive optical limiters, especially against laser lights with longer pulses.
Synthesis and Biological Evaluation of 1‐Deoxy‐5‐hydroxysphingosine Derivatives
Authors: Esteve Judit , Lorente Adriana , Romea Pedro , Urpí Fèlix , Ríos‐Luci Carla , Padrón José M.
Published: December 2010

A sequential transformation based on the titanium‐mediated aldol addition of (S)‐1‐bromo‐3‐(tert‐butyldimethylsilyloxy)‐2‐butanone, a chiral lactate‐derived ketone, to tetradecanal followed by reduction of the ensuing aldolate afforded the corresponding syn‐1,3‐diol as a single diastereomer. Debromination and further manipulation of this intermediate allowed the efficient synthesis of two enantiopure 1‐deoxy‐5‐hydroxysphingosines, which exhibit promising biological activity against a representative panel of human cancer lines.
Scope and Selectivity of Heterogeneous Rh0‐Catalyzed Tandem Dehydrocoupling/Hydrogenation Using Me2NH·BH3 as a Stoichiometric H2 Source
Authors: Sloan Matthew E. , Staubitz Anne , Lee Kajin , Manners Ian
Published: December 2010

The catalytic dehydrocoupling of Me2NH·BH3 (1) by Rh/Al2O3 (2) has been shown to act as an efficient hydrogenation and reduction system for a variety of organic substrates. A range of functional groups have been reduced, but chloro, bromo and iodo substituents, epoxide and nitrile groups were found to be stable under the reaction conditions, allowing chemoselective hydrogenation reactions to be performed. This reduction has also been shown to proceed cleanly under atmospheric air for a few representative examples of alkene and nitro functional groups.
Synthesis and Utility of 2‐Halo‐O6‐(benzotriazol‐1‐yl)‐Functionalized Purine Nucleosides
Authors: Devine Shane M. , Scammells Peter J.
Published: December 2010

An efficient synthesis of 2‐halo‐O6‐(benzotriazol‐1‐yl)‐substituted purine nucleosides has been accomplished via (benzotriazol‐1‐yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP)‐mediated coupling and subsequent halogenation via diazotization of the 2‐amino group of various protected guanosines and directly from guanosine itself. These products are amenable to substitution and coupling reactions in the 2‐ and 6‐positions and, accordingly, provide efficient access to highly functionalized purine nucleosides.
Electron‐Deficient Aryl β‐Diketones: Synthesis and Novel Tautomeric Preferences
Authors: Sloop Joseph C. , Boyle Paul D. , Fountain Augustus W. , Pearman William F. , Swann Jacob A.
Published: December 2010

Fluorinated aryl β‐diketones were prepared using Claisen and electrophilic fluorination methods. The keto–enol and enol–enol tautomerism of these compounds were examined in the solid state, as neat liquids and in polar, aprotic solution by crystallography and spectroscopy. Neat‐liquid spectroscopic measurements as well as single crystal X‐ray crystallographic results for selected electron‐deficient aryl β‐diketones suggest a single, chelated cis‐enol isomer that is conjugated with the aryl ring. In polar aprotic solvents, nonfluorinated aryl β‐diketones equilibrate rapidly from the chelated cis‐enol form to a tautomeric mixture of cis‐chelated enol and a substantial proportion of the diketone form, trifluoromethylated aryl β‐diketones show only limited equilibration from the chelated cis‐enol to the diketone form, with 2‐fluoro‐1‐aryl β‐diketones again displaying only the diketonic form.
Cyclization of 2‐Alkynylallyl Alcohols to Highly Substituted Furans by Gold(I)–Carbene Complexes
Authors: Hashmi A. Stephen K. , Häffner Tobias , Rudolph Matthias , Rominger Frank
Published: December 2010

Various 2‐alkynylallyl alcohols were synthesized by a generally applicable Sonogashira coupling protocol. Subsequent gold‐catalyzed transformation was investigated. The use of AuI catalysts bearing carbene ligands, of either the N‐heterocyclic carbene or nitrogen acyclic carbene type, delivered the desired products with low catalyst loadings and under very mild reaction conditions. A broad array of substrates was tested, including alkyl‐, alkenyl‐, and aryl‐substituted alkynes, as well as substrates with two alkynyl moieties. The methodology turned out to have a broad scope. Secondary allyl alcohols were also tolerated, and the resulting trisubstituted furans could be isolated in high yields.
Ruthenium‐Catalyzed Synthesis of 1,5‐Dichlorides by Sequential Intermolecular Kharasch Reactions (Eur. J. Org. Chem. 2/2011)
Authors: Thommes Katrin , Fernández‐Zúmel Mariano A. , Buron Charlotte , Godinat Aurélien , Scopelliti Rosario , Severin Kay
Published: December 2010

The cover picture shows Mariano Fernández‐Zúmel taking two steps at the same time. In the laboratory, two‐step reactions have been realized in one pot by coupling 1,1‐dichlorides with two olefins in sequential atom transfer radical addition (ATRA) reactions. Details are discussed in the article by K. Severin et al. on p. 249 ff.
Glutamate and the biology of gliomas
Authors: de Groot John , Sontheimer Harald
Published: December 2010

Several important and previously unrecognized roles for the neurotransmitter glutamate in the biology of primary brain tumors have recently been elucidated. Glutamate is produced and released from glioma cells via the system xc− cystine glutamate transporter as a byproduct of glutathione synthesis. Glutamate appears to play a central role in the malignant phenotype of glioma via multiple mechanisms. By binding to peritumoral neuronal glutamate receptors, glutamate is responsible for seizure induction and similarly causes excitotoxicity, which aids the expansion of tumor cells into the space vacated by destroyed tissue. Glutamate also activates ionotropic and metabotropic glutamate receptors on glioma cells in a paracrine and autocrine manner. α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoaxazolepropionate acid (AMPA) glutamate receptors lack the GluR2 subunit rendering them Ca2+ permeable and capable of activating the AKT and MAPK pathways. Furthermore, these receptors are critical in aiding the invasion of glioma cells into normal brain. AMPA‐Rs accumulate at focal adhesion sites where they may indirectly mediate interactions between the extracellular matrix and integrins. Glutamate receptor stimulation results in activation of focal adhesion kinase, which is critical to the regulation of growth factor and integrin‐stimulated cell motility and invasion. The multitude of effects of glutamate on glioma biology supports the rationale for pharmacological targeting of glutamate receptors and transporters. Several ongoing and recently completed clinical trials are exploring the therapeutic potential of interrupting glutamate‐mediated brain tumor growth. © 2010 Wiley‐Liss, Inc.
Development and composition of irrigation in India: Temporal trends and regional patterns
Authors: Narayanamoorthy A.
Published: December 2010

India's irrigation sector is one of the largest in the world. The government alone has invested about Rs. 1556 billion (in current prices) in the irrigation sector as of 2001–2002. The irrigated area has increased from 20.9 million ha in 1950–1951 to 78.4 million ha in 2002–2003, an increase of almost four times. A large number of studies have analysed the impact of irrigation on various parameters. However, not many studies have analysed the direction of changes in the irrigated area across major sources and states. Therefore, an in‐depth analysis on the trends and development of irrigation is essential to frame appropriate irrigation policies for the future. In this study, an attempt is made to analyse the past development of the irrigated area across states using time series data from 1950–1951 to 2002–2003. This study shows that the growth in irrigated area across the states and sources has decelerated substantially during the post‐green revolution period (1980–1981 to 2002–2003) as compared to the green revolution period (1965–1966 to 1980–1981). The low‐cost source of irrigation, namely tanks, has declined sharply since the mid‐1960s, which may create livelihood problems for farmers relying on this source. Copyright © 2010 John Wiley & Sons, Ltd.
Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow
Authors: Jacome-Galarza Christian E , Lee Sun-Kyeong , Lorenzo Joseph A , Aguila Hector Leonardo
Published: December 2010

Parathyroid hormone (PTH) increases both the number of osteoclast in bone and the number of early hematopoietic stem cells (HSCs) in bone marrow. We previously characterized the phenotype of multiple populations of bone marrow cells with in vitro osteoclastogenic potential in mice. Here we examined whether intermittent administration of PTH influences these osteoclast progenitor (OCP) populations. C57BL/6 mice were treated with daily injections of bPTH(1–34) (80 µg/kg/day) for 7 or 14 days. We found that PTH caused a significant increase in the percentage of TN/CD115+CD117high and TN/CD115+CD117int cells (p < .05) in bone marrow on day 7. In contrast, PTH decreased the absolute number of TN/CD115+CD117low cells by 39% on day 7 (p < .05). On day 14, there was no effect of PTH on osteoclast progenitor distribution in vivo. However, PTH treatment for 7 and 14 days did increase receptor activator of NF-κB ligand (RANKL)– and macrophage colony-stimulating factor (M-CSF)–stimulated in vitro osteoclastogenesis and bone resorption in TN/CD115+ cells. In the periphery, 14 days of treatment increased the percentage and absolute numbers of HSCs (Lin−CD117+Sca-1+) in the spleen (p < .05). These data correlated with an increase in the percent and absolute numbers of HSCs in bone marrow on day 14 (p < .05). Interestingly, the effects on hematopoietic progenitors do not depend on osteoclast resorption activity. These results suggest that in vivo PTH treatment increased in vitro osteoclastogenesis and resorption without altering the number of osteoclast precursors. This implies that in vivo PTH induces sustained changes, possibly through an epigenetic mechanism, in the in vitro responsiveness of the cells to M-CSF and RANKL. © 2011 American Society for Bone and Mineral Research.
ACSL3 and GSK‐3β are essential for lipid upregulation induced by endoplasmic reticulum stress in liver cells
Authors: Chang Yung‐Sheng , Tsai Chien‐Ting , Huangfu Chien‐An , Huang Wen‐Ya , Lei Huan‐Yao , Lin Chiou‐Feng , Su Ih‐Jen , Chang Wen‐Tsan , Wu Pei‐Huan , Chen Ya‐Ting , Hung Jui‐Hsiang , Young Kung‐Chia , Lai Ming‐Derg
Published: December 2010

The endoplasmic reticulum (ER) is essential for lipid biosynthesis, and stress signals in this organelle are thought to alter lipid metabolism. Elucidating the mechanisms that underlie the dysregulation of lipid metabolism in hepatocytes may lead to novel therapeutic approaches for the treatment of lipid accumulation. We first tested the effects of several inhibitors on lipid dysregulation induced by tunicamycin, an ER stress inducer. Triacsin C, an inhibitor of long‐chain acyl‐CoA synthetase (ACSL) 1, 3, and 4, was the most potent among these inhibitors. We then analyzed the expression of the ACSL family during ER stress. The expression of ACSL3 was induced by ER stress in HuH‐7 cells and in mice livers. ACSL3 shRNA, but not ACSL1 shRNA, inhibited the induction of lipid accumulation. GSK‐3β inhibitors attenuated ACSL3 expression and the lipid accumulation induced by ER stress in HuH‐7 cells. shRNA that target GSK‐3β also inhibited the upregulation of ACSL3 and lipid accumulation in HuH‐7 and HepG2 cells. The hepatitis B virus mutant large surface protein, which is known to induce ER stress, increased the lipid content of cells. Similarly, Triacsin C, and GSK‐3β inhibitors abrogated the lipid dysregulation caused by the hepatitis B virus mutant large surface protein. Altogether, ACSL3 and GSK‐3β represent novel therapeutic targets for lipid dysregulation by ER stress. J. Cell. Biochem. 112: 881–893, 2011. © 2010 Wiley‐Liss, Inc.
Usp7 and Uhrf1 control ubiquitination and stability of the maintenance DNA methyltransferase Dnmt1
Authors: Qin Weihua , Leonhardt Heinrich , Spada Fabio
Published: December 2010

In mammals Dnmt1 is the DNA methyltransferase chiefly responsible for maintaining genomic methylation patterns through DNA replication cycles, but how its maintenance activity is controlled is still not well understood. Interestingly, Uhrf1, a crucial cofactor for maintenance of DNA methylation by Dnmt1, is endowed with E3 ubiquitin ligase activity. Here, we show that both Dnmt1 and Uhrf1 coprecipitate with ubiquitin specific peptidase 7 (Usp7), a de‐ubiquitinating enzyme. Overexpression of Uhrf1 and Usp7 resulted in opposite changes in the ubiquitination status and stability of Dnmt1. Our findings suggest that, by balancing Dnmt1 ubiquitination, Usp7 and Uhrf1 fine tune Dnmt1 stability. J. Cell. Biochem. 112: 439–444, 2011. © 2010 Wiley‐Liss, Inc.
Positive regulation of inositol 1,4,5‐trisphosphate‐induced ca2+ release by mammalian target of rapamycin (mTOR) in RINm5F cells
Authors: Frégeau Marc‐Olivier , Régimbald‐Dumas Yannik , Guillemette Gaétan
Published: December 2010

The inositol 1,4,5‐trisphosphate receptor (IP3R), a ligand‐gated Ca2+ channel, is the main regulator of intracellular Ca2+ mobilization in non‐excitable cells. An emerging body of evidence suggests that specific regulatory control of the Ca2+ signaling pathway is modulated by the activation of additional signaling pathways. In the present study, we investigated the influence of the PI3‐kinase/mammalian target of rapamycin (mTOR) pathway on the activity of the IP3R/Ca2+ signaling pathway in RINm5F cells. We used a co‐immunoprecipitation approach to show that mTOR physically interacts with IP3R‐3 in an mTOR activity‐dependent manner. We also showed that IP3R is phosphorylated by mTOR in cellulo. All the conditions known to modulate mTOR activity (IGF‐1, wortmannin, rapamycin, PP242, and nutrient starvation) were shown to modify carbachol‐induced Ca2+ signaling in RINm5F cells. Lastly, we used an assay that directly measures the activity of IP3R, to show that mTOR increases the apparent affinity of IP3R. Given that mTOR controls cell proliferation and cell homeostasis, and that Ca2+ plays a key role in these two phenomena, it follows that mTOR facilitates IP3R‐mediated Ca2+ release when the nutritional status of cells requires it. J. Cell. Biochem. 112: 723–733, 2011. © 2011 Wiley‐Liss, Inc.
Cdk1 is required for the self‐renewal of mouse embryonic stem cells
Authors: Zhang Wei Wei , Zhang Xiao Jie , Liu Hui Xian , Chen Jie , Ren Yong Hong , Huang Deng Gao , Zou Xiang Hong , Xiao Wei
Published: December 2010

Cyclin‐dependent kinase 1 (Cdk1) is indispensible for the early development of the embryo. However, its role in maintaining the undifferentiated state of the embryonic stem (ES) cells remains unknown. In this study, we dissected the function of Cdk1 in mouse ES cells by RNA‐interference and gene expression analyses. Cdk1 expression is tightly correlated with the undifferentiated state of the ES cells. Upon differentiation, Cdk1 expression reduced drastically. Cdk1 knock‐down by RNA interference resulted in the loss of proliferation and colony formation potential of the ES cells. Consequentially, expression of self‐renewal genes was reduced while differentiation markers such as Cdx2 were induced. Our results suggest a role for Cdk1 in maintaining the unique undifferentiated and self‐renewing state of the mouse ES cells. J. Cell. Biochem. 112: 942–948, 2011. © 2010 Wiley‐Liss, Inc.
Imaging the recruitment of cancer‐associated fibroblasts by liver‐metastatic colon cancer
Authors: Suetsugu Atsushi , Osawa Yosuke , Nagaki Masahito , Saji Shigetoyo , Moriwaki Hisataka , Bouvet Michael , Hoffman Robert M.
Published: December 2010

The tumor microenvironment (TME) is critical for tumor growth and progression. However, the formation of the TME is largely unknown. This report demonstrates a color‐coded imaging model in which the development of the TME can be visualized. In order to image the TME, a green fluorescent protein (GFP)‐expressing mouse was used as the host which expresses GFP in all organs but not the parenchymal cells of the liver. Non‐colored HCT‐116 human colon cancer cells were injected in the spleen of GFP nude mice which led to the formation of experimental liver metastasis. TME formation resulting from the liver metastasis was observed using the Olympus OV100 small animal fluorescence imaging system. HCT‐116 cells formed tumor colonies in the liver 28 days after cell transplantation to the spleen. GFP‐expressing host cells were recruited by the metastatic tumors as visualized by fluorescence imaging. A desmin positive area increased around and within the liver metastasis over time, suggesting cancer‐associated fibroblasts (CAFs) were recruited by the liver metastasis which have a role in tumor progression. The color‐coded model of the TME enables its formation to be visualized at the cellular level in vivo, in real‐time. This imaging model of the TME should lead to new visual targets in the TME. J. Cell. Biochem. 112: 949–953, 2011. © 2010 Wiley‐Liss, Inc.
Cellular prion proteins in human platelets show a phenotype different to those in brain tissues
Authors: Kuczius Thorsten , Kleinert Julia , Karch Helge , Sibrowski Walter , Kelsch Reinhard
Published: December 2010

Prion diseases are characterized by high accumulation of infectious prion proteins (PrPSc) in brains. PrPSc are propagated by the conversion of host‐encoded cellular prion proteins (PrPC) which are essential for developing the disease but are heterogeneously expressed in brains. The disease can be transmitted to humans and animals through blood and blood products, however, little attention has been given to molecular characterization of PrPC in blood cells. In this presented study, we characterized phenotypically PrPC of platelets (plt) and characterized the proteins regarding their glycobanding profiles by quantitative immunoblotting using a panel of monoclonal antibodies. The glycosylation patterns of plt and brain PrPC were compared using the ratios of di‐, mono‐, and non‐glycosylated prions. The detergent solubility of plt and brain PrPC was also analyzed. The distinct banding patterns and detergent solubility of plt PrPC differed clearly from the glycosylation profiles and solubility characteristics of brain PrPC. Plt PrPC exhibited single or only few prion protein types, whereas brain PrPC showed more extensive banding patterns and lower detergent solubility. Plt PrPC are post‐translational modified differently from PrPC in brain. These findings suggest other or less physiological functions of plt PrPC than in brain. J. Cell. Biochem. 112: 954–962, 2011. © 2010 Wiley‐Liss, Inc.
How dynein and microtubules rotate the nucleus
Authors: Wu Jun , Lee Kristen C. , Dickinson Richard B. , Lele Tanmay P.
Published: December 2010

In living cells, a fluctuating torque is exerted on the nuclear surface but the origin of the torque is unclear. In this study, we found that the nuclear rotation angle is directionally persistent on a time scale of tens of minutes, but rotationally diffusive on longer time scales. Rotation required the activity of the microtubule motor dynein. We formulated a model based on microtubules undergoing dynamic instability, with tensional forces between a stationary centrosome and the nuclear surface mediated by dynein. Model simulations suggest that the persistence in rotation angle is due to the transient asymmetric configuration of microtubules exerting a net torque in one direction until the configuration is again randomized by dynamic instability. The model predicts that the rotational magnitude must depend on the distance between the nucleus and the centrosome. To test this prediction, rotation was quantified in patterned cells in which the cell's centrosome was close to the projected nuclear centroid. Consistent with the prediction, the angular displacement was found to decrease in these cells relative to unpatterned cells. This work provides the first mechanistic explanation for how nuclear dynein interactions with discrete microtubules emanating from a stationary centrosome cause rotational torque on the nucleus. J. Cell. Physiol. 226: 2666–2674, 2011. © 2010 Wiley‐Liss, Inc.
A multi‐center study on the surgical management of metastatic disease to adrenal glands
Authors: Valeri Andrea , Bergamini Carlo , Tozzi Fabiano , Martellucci Jacopo , Di Costanzo Francesco , Antonuzzo Lorenzo
Published: December 2010

Background

In the management of adrenal lesions in oncological patients, many issues are still controversial: morphological signs of suspected malignancy, accuracy of imaging examinations, use of fine needle aspiration (FNA), and the role of laparoscopy. The present study attempts to address these questions through the evaluation of the management of adrenal metastases (AM) in a wide cohort of patients included in the Italian Register of Endoscopic Adrenal Surgery.

Methods

In January 2009, all patients recorded on the Register were evaluated, on the basis of CT scan, MRI, and FNA. The diagnostic, surgical, and follow‐up data of 95 patients with pre‐operative AM diagnosis have been reviewed. On the basis of the fulfilled criteria three patterns were identified: “diagnostic”, “suspect,” and “non‐diagnostic.”

Results

CT scan sensitivity was 41.5%/77.9% and specificity was 54.5%/90.9% for “diagnostic”/“diagnostic” + “suspect” examinations, respectively. MRI sensitivity was 15.7%/78.9% and specificity was non‐determinate/83.3% for “diagnostic”/“diagnostic” + “suspect” exams, respectively. Sensitivity of FNA was 33.3%. About surgery, conversions rate was 16.6%; no mortality or re‐operations were reported; complications rate was 10.7%; and no relation was noted between tumor size and surgical outcome. Mean survival was 32 months; 5‐year survival was 23%, independent of AM size; survival for lung AM was similar to that of breast and kidney AM.

Conclusions

Laparoscopy for AM, in expert hand, seems to be a feasible and oncologically safe approach. Due to the unsatisfactory diagnostic accuracy for AM, every oncological patient with suspect adrenal lesions should be encouraged to undergo this surgical procedure. J. Surg. Oncol. 2011; 103:400–405. © 2010 Wiley‐Liss, Inc.
Chemo‐Physical and Biological Evaluation of Poly(L‐lysine)‐Grafted Chitosan Copolymers Used for Highly Efficient Gene Delivery
Authors: Yu Haijun , Deng Chao , Tian Huayu , Lu Tiancheng , Chen Xuesi , Jing Xiabin
Published: December 2010

For the success of non‐viral gene delivery, it is of great importance to develop gene vectors with high efficiency but low toxicity. We demonstrate that PLL‐grafted chitosan copolymers combine the advantages of PLL with its good pDNA‐binding ability and of chitosan with its good biocompatibility. The chemo‐physical properties of the prepared Chi‐g‐PLL copolymers are thoroughly characterized. The in vitro transfection study shows that the copolymers have a much higher gene transfer ability than the starting materials chitosan and PLL. A positive correlation between PLL chain lengths and transfection efficiency of the copolymers is found. Our results suggest that these novel Chi‐g‐PLL copolymers are good candidates for gene delivery in vivo.

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Direct Nanopatterning of Silsesquioxane/Poly(ethylene glycol) Blends with High Stability and Nonfouling Properties
Authors: Lee Bong Kuk , Kawai Tomoji , Chung Bong Hyun
Published: December 2010

A free‐radical‐polymerizable SSQ/PEG blend with direct patternability has been proposed as an ideal nonfouling material for nanostructure‐based biomedical applications. Cured SSQ/PEG networks show an UV transparency of >90% at 365 nm, high resistance to organic/aqueous solutions, hydrophilicity and Young's moduli of 1.898–2.815 GPa. SSQ/PEG patterns with 25‐nm linewidths, 25‐nm spacing, and an aspect ratio of 4:1 were directly fabricated on transparent substrates by UV embossing, and cured SSQ/PEG networks with long‐term stability under chemical, thermal, and biological stress showed strong resistance to the nonspecific adsorption of biomolecules. These characteristics may offer a new strategy for the development of a number of medical nanodevice applications such as labs‐on‐a‐chip.

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Advances in Mucoadhesion and Mucoadhesive Polymers
Authors: Khutoryanskiy Vitaliy V.
Published: December 2010

Mucoadhesion is the ability of materials to adhere to mucosal membranes in the human body and provide a temporary retention. This property has been widely used to develop polymeric dosage forms for buccal, oral, nasal, ocular and vaginal drug delivery. Excellent mucoadhesive properties are typical for hydrophilic polymers possessing charged groups and/or non‐ionic functional groups capable of forming hydrogen bonds with mucosal surfaces. This feature article considers recent advances in the study of mucoadhesion and mucoadhesive polymers. It provides an overview on the structure of mucosal membranes, properties of mucus gels and the nature of mucoadhesion. It describes the most common methods to evaluate mucoadhesive properties of various dosage forms and discusses the main classes of mucoadhesives.

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Self‐Assembly Strategy for the Preparation of Polymer‐Based Nanoparticles for Drug and Gene Delivery
Authors: Chen Si , Cheng Si‐Xue , Zhuo Ren‐Xi
Published: December 2010

Nanoparticulate drug‐delivery systems have attained much importance because of their injectable property, the possibility to achieve passive targeting and active targeting, and unique advantages to realize stimuli tailored delivery. Molecular self‐assembly is a powerful method for fabricating polymer‐based nanoparticles, which involves various driving forces, such as hydrophobic interactions, electrostatic interactions, stereocomplexation, host/guest interactions and hydrogen bonding. By fine tuning one or many types of these interactions, self‐assemblies with a wide range of structures and functions could be fabricated. In this article, recent developments in different self‐assembly strategies for the preparation of polymer‐based nanoparticulate delivery systems are discussed.

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A new approach to improve high temperature corrosion resistance of thermally sprayed coatings by using electrochemical corrosion tests
Authors: Neddemeyer T. , Mocker M. , Faulstich M.
Published: December 2010

In order to increase reliability and lifetime of heat exchangers in waste‐to‐energy plants corrosion resistant thermally sprayed coatings are applied in a higher extent. From the selection of a plant specific spray material and process via laboratory and field experiments up to a successful coating a high amount of time and money is necessary. In particular, experiments in corrosive surroundings at high temperature which are needed to optimize the coating quality are time‐consuming. In order to decrease development times and to reduce costs, corrosion resistance of a thermally sprayed coating under high temperature conditions is compared with its behavior in an aqueous solution. If the high temperature corrosion resistance can be forecast by electrochemical tests, a fast, efficient and cheap possibility to improve the coating quality would be available and the efforts for tests in high temperature environments could be decreased. To accomplish this objective, Diamalloy 1005 was sprayed with the APS‐process on a ferritic steel. Since the performance of thermally sprayed coatings is not only influenced by the coating material but also by the spraying parameters, three different spray parameter sets were used.

After analyzing the results of the corrosion tests under high temperature conditions and in aqueous solution an identical assessment of the spray parameter‐specific corrosion protection could be obtained. Ongoing field tests in a waste‐to‐energy plant are expected to prove the laboratory results. So, a first step in the development of a fast, efficient and cheap method to predict the high temperature corrosion resistance of a thermally sprayed coating might have been done.
Microstructural investigation of PGM‐based alloy coatings for oxidation protection
Authors: Song Y. , Zhou C. , Murakami H.
Published: December 2010

It is well known that Pt addition significantly improves the resistance of aluminide coatings to high‐temperature oxidation and hot corrosion, which has led to the widespread application of Pt modified aluminide coatings on the superalloy components of advanced gas turbine engines.

Other platinum group metals (PGMs) such as Ir and Ru attract researchers for high temperature applications. In this study, oxidation properties of Pt‐Ir and Pt‐Ru based alloy coatings were investigated. Pt, Ru, and Ir were electroplated on a directionally solidified Ni‐base superalloy DZ125. The cyclic oxidation test revealed that both Pt‐Ir and Pt‐Ru alloys exhibited good oxidation performance. The effect of substrate alloy and coating compositions on microstructural changes during cyclic oxidation tests were discussed.
Behaviour of ferritic stainless steels subjected to dry biogas atmospheres at high temperatures
Authors: Promdirek P. , Lothongkhum G. , Chandra‐ambhorn S. , Wouters Y. , Galerie A.
Published: December 2010

The objective of this study is to understand the high temperature corrosion behaviour of the ferritic stainless steel type AISI 441 (18CrTiNb), a candidate for SOFC interconnectors, under dry synthetic fermentation biogas (CH4 + CO2 mixtures), possibly used at the anode side of the cell. Thermodynamic analysis showed that, in such mixtures, the partial pressure of oxygen lies in the range of 10−23 to 10−20 bar for temperature between 700 and 900 °C and that the formation of solid carbon may take place in several conditions. XRD results confirmed the formation of Cr2O3 and Mn‐Cr spinel, with a mixture of internal carbides. In this temperature range, kinetic experiments showed linear mass change. Comparing with the linear rate constants of 441 oxidised in pure CO2, corrosion in biogas was larger and increased with increasing the methane content in the biogas. The surface morphology of the corroded specimens showed a dense oxide scale at temperatures less than 800 °C, serving as an efficient barrier to carbon penetration. However, when the temperature reaches 900 °C, cracks and pores appear in the oxide scale, carbon can precipitate and diffuse easier than at 800 °C and may lead to internal carbide formation. In such biogas atmospheres, 800 °C seems the maximum operating temperature of devices containing this ferritic stainless steel.
A thermodynamic study of the gaseous potassium chemistry in the convection sections of biomass fired boilers
Authors: Blomberg T.
Published: December 2010

Thermodynamic calculations of the gaseous potassium species in boiler flue gases are presented. Results show that if the K(g)/Cl(g) molar ratio is still higher than 1 after the K2SO4(s) aerosol formation at high gas temperatures, the excess potassium is in the form of KOH(g). K(g)/Cl(g) molar ratios at the inlet of the convection section for biomass fired boilers were estimated from the chemical analysis of the fuels, with the assumption that all the fuel sulfur had reacted to K2SO4(s) aerosols before the inlet of the convection section. 0–100% conversion of fuel alkali to vaporized alkali was calculated. Generally, if the conversion was more than 60%, the calculated ratios for biomass fuels were higher than 1. Furthermore, due to the thermodynamic instability of K2CO3(g), it is likely that the formation of K2CO3(s) on the heat transfer surfaces follows a heterogeneous route where KOH(l,s) is transformed to K2CO3(s) at the surface, not in the gas phase. This leads to a possible formation of a basic salt melt on the heat transfer surfaces and thus alloying with Cr may be ineffective in improving the hot corrosion resistance of steels in these environments. Based on the literature data of oxide solubilities in basic alkali melts, it is suggested that alloying with Ni or Co will provide better protection in these applications.
Polymer Loops vs. Brushes on Surfaces: Adsorption, Kinetics, and Viscoelastic Behavior of α,ω‐Thiol Telechelics on Gold
Authors: Patton Derek , Knoll Wolfgang , Advincula Rigoberto C.
Published: December 2010

Telechelic thiopolymers were explored towards formation of doubly‐bound (polymer loops) vs. singly‐bound (polymer brushes) chains on gold substrates. The conformation, adsorption kinetics, and viscoelastic properties of the α,ω‐dithiol and monothiol PS telechelics were investigated by means of XPS and QCM‐D techniques. The oxidation behavior of the free thiol proved to be important for distinguishing doubly‐bound vs. singly‐bound chains. The results show a critical dependence of $\overline {M} _{{\rm n}} $ on the ability to obtain polymer loops. Comparison with unperturbed dimensions obtained by scaling theory show that the loop is less stretched and occupies more lateral space than the brush. The results are important in demonstrating the different and perhaps superior properties of polymer loops vs. singly‐bound polymer brushes.

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Ni‐Catalyzed Polymerization of Poly(3‐alkoxythiophene)s
Authors: Van den Bergh Karlien , De Winter Julien , Gerbaux Pascal , Verbiest Thierry , Koeckelberghs Guy
Published: December 2010

The Ni‐catalyzed polymerization of P3AOTs was studied and compared with the controlled chain‐growth polymerization of P3ATs. By varying the ratio of the initial monomer concentration to the initiator concentration, no linear dependence of the molar mass was observed, revealing that the polymerization does not proceed via a controlled mechanism. This was also confirmed by analyzing the end‐groups of the polymer with MALDI‐TOF mass spectrometry. To acquire more information on the polymerization mechanism, the formation of the actual monomer and the polymerization reaction were studied into more detail. These experiments proved that the polymerization proceeds via a chain‐growth mechanism, although not in a controlled way.

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Polyester Obtained by Anionic Polymerization of Ethylketene
Authors: Hayki Najib , Desilles Nicolas , Burel Fabrice
Published: December 2010

Aldoketenes are well known to undergo fast dimerization and trimerization even at low temperatures but have never been polymerized so far. For the first time, ethylketene, synthesized following the Staudinger procedure modified by McCarney, was polymerized anionically in THF with various initiators, at different temperatures (–40 and –78 °C), and with several monomer/initiator ratios. The resulting polymer was composed exclusively of polyester units, and the initiator did not affect the stereoregularity. Molecular weights up to 24 000 g · mol−1 were obtained with lithium‐based initiators. Transfer reactions and the failure to make block copolymers highlighted a non‐living polymerization. Tg values around –18 °C and thermal stability up to 160 °C were measured.

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Nanostructured Heteroarm Star Block Terpolymers via an Extension of the “In–Out” Polymerization Route
Authors: Linardatos George , Tsoukleri Georgia , Parthenios John , Galiotis Costas , Monticelli Orietta , Russo Saverio , Tsitsilianis Constantinos
Published: December 2010

In this communication an extended “in–out” polymerization method is presented, which leads to the synthesis of novel heteroarm star block terpolymers of the type An(B‐b‐C)n. A four step/one‐pot synthetic procedure is pursued using anionic polymerization under an inert atmosphere. The resulted star‐shaped terpolymer consists of a divinyl benzene nodule bearing pure polystyrene and poly(hexyl methacrylate)‐block‐poly(methyl methacrylate) diblock copolymer arms. It is shown that this kind of star terpolymers can self‐assemble in the bulk forming lamellae mesophase by arm and block segregation. The mechanical properties of the terpolymer have been examined in detail. Finally, the proposed synthetic procedure can be easily employed in other controlled polymerization methods.

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