bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted Cellular Uptake and siRNA Silencing by Quantum‐Dot Nanoparticles Coated with β‐Cyclodextrin Coupled to Amino Acids
Authors: Zhao Mei‐Xia , Li Jin‐Ming , Du Lingyan , Tan Cai‐Ping , Xia Qing , Mao Zong‐Wan , Ji Liang‐Nian 
Published: April 2011

AbstractQuantum dots (QDs) have the potential to serve as photostable beacons to track siRNA delivery, which is fast becoming an attractive approach to probe gene function in cells. In this paper, we synthesized QD nanoparticles coated with β‐cyclodextrin (β‐CD) coupled to amino acids with different surface charges (positive, negative, and neutral) through direct ligand‐exchange reactions and used them to deliver siRNA. We found that these QDs are diffluent in biological buffer with high colloidal stability and have strong optical emission properties similar to those of tri‐n‐octylphosphine oxide (TOPO)‐coated QDs and also have a long fluorescence lifetime (12.5 ns for L‐His‐β‐CD‐coated CdSe/ZnSe QDs). The results of in vitro cytotoxicity and internalization of these modified QDs in normal and cancer cells showed that the β‐CD coupled to amino acid outlayers greatly improved the biocompatibility of QDs, and conferred with lower cytotoxicity even at very high concentration. In particular, the L‐His‐β‐CD‐coated CdSe/ZnSe QDs presented lower cytotoxicity to these cells (CC50 value is 180.6±3.4 μg mL−1 in ECV‐304 cells for 48 h). Transmission electron microscope (TEM) images showed that the QDs were localized in vesicles in the cytoplasm of the cells. Furthermore, compared with existing transfection agents, gene‐silencing efficiency of the modified QDs was slightly improved for HPV18 E6 gene in HeLa cells by gel electrophoresis analysis. Finally, the unique optical properties of QDs allow visible imaging of siRNA delivery in live cells. Taken together, our study not only provides new insights into the mechanisms of amino acid mediated delivery, but also greatly facilities the monitoring of gene‐silencing studies.
Benzyl and Naphthalene Methylphosphonic Acid Inhibitors of Autotaxin with Anti‐invasive and Anti‐metastatic Activity
Authors: Gupte Renuka , Patil Renukadevi , Liu Jianxiong , Wang Yaohong , Lee Sue C. , Fujiwara Yuko , Fells James , Bolen Alyssa L. , Emmons‐Thompson Karin , Yates C. Ryan , Siddam Anjaih , Panupinthu Nattapon , Pham Truc‐Chi T. , Baker Daniel L. , Parrill Abby L. , Mills Gordon B. , Tigyi Gabor , Miller Duane D. 
Published: April 2011

AbstractAutotaxin (ATX, NPP2) is a member of the nucleotide pyrophosphate phosphodiesterase enzyme family. ATX catalyzes the hydrolytic cleavage of lysophosphatidylcholine (LPC) by lysophospholipase D activity, which leads to generation of the growth‐factor‐like lipid mediator lysophosphatidic acid (LPA). ATX is highly upregulated in metastatic and chemotherapy‐resistant carcinomas and represents a potential target to mediate cancer invasion and metastasis. Herein we report the synthesis and pharmacological characterization of ATX inhibitors based on the 4‐tetradecanoylaminobenzylphosphonic acid scaffold, which was previously found to lack sufficient stability in cellular systems. The new 4‐substituted benzylphosphonic acid and 6‐substituted naphthalen‐2‐ylmethylphosphonic acid analogues block ATX activity with Ki values in the low micromolar to nanomolar range against FS3, LPC, and nucleotide substrates through a mixed‐mode inhibition mechanism. None of the compounds tested inhibit the activity of related enzymes (NPP6 and NPP7). In addition, the compounds were evaluated as agonists or antagonists of seven LPA receptor (LPAR) subtypes. Analogues 22 and 30 b, the two most potent ATX inhibitors, inhibit the invasion of MM1 hepatoma cells across murine mesothelial and human vascular endothelial monolayers in vitro in a dose‐dependent manner. The average terminal half‐life for compound 22 is 10±5.4 h and it causes a long‐lasting decrease in plasma LPA levels. Compounds 22 and 30 b significantly decrease lung metastasis of B16‐F10 syngeneic mouse melanoma in a post‐inoculation treatment paradigm. The 4‐substituted benzylphosphonic acids and 6‐substituted naphthalen‐2‐ylmethylphosphonic acids described herein represent new lead compounds that effectively inhibit the ATX–LPA–LPAR axis both in vitro and in vivo.
Inhibition of Mycobacterium tuberculosis Methionine Aminopeptidases by Bengamide Derivatives
Authors: Lu Jing‐Ping , Yuan Xiu‐Hua , Yuan Hai , Wang Wen‐Long , Wan Baojie , Franzblau Scott G. , Ye Qi‐Zhuang 
Published: April 2011

AbstractMethionine aminopeptidase (MetAP) carries out an essential function of protein N‐terminal processing in many bacteria and is a promising target for the development of novel antitubercular agents. Natural bengamides potently inhibit the proliferation of mammalian cells by targeting MetAP enzymes, and the X‐ray crystal structure of human type 2 MetAP in complex with a bengamide derivative reveals the key interactions at the active site. By preserving the interactions with the conserved residues inside the binding pocket while exploring the differences between bacterial and human MetAPs around the binding pocket, seven bengamide derivatives were synthesized and evaluated for inhibition of MtMetAP1a and MtMetAP1c in different metalloforms, inhibition of M. tuberculosis growth in replicating and non‐replicating states, and inhibition of human K562 cell growth. Potent inhibition of MtMetAP1a and MtMetAP1c and modest growth inhibition of M. tuberculosis were observed for some of these derivatives. Crystal structures of MtMetAP1c in complex with two of the derivatives provided valuable structural information for improvement of these inhibitors for potency and selectivity.
Soft tissue sarcoma diagnosed subsequent to lymphoma is associated with prior radiotherapy and decreased survival
Authors: Katz Steven C. , Baldwin Keith , Karakousis Giorgos , Moraco Nicole , Buglino Anthony , Singer Samuel , Brennan Murray F. 
Published: April 2011

AbstractBACKGROUND:Cancer survivors are at increased risk for second malignancies, and vigilance is thus required. The authors sought to determine whether there was an association among lymphoma, sarcoma, and the associated treatments for these diseases.METHODS:From the authors' prospective soft tissue sarcoma (STS) database of 8240 patients, they identified 112 patients with STS and lymphoma treated from 1982 to 2009 who had complete follow‐up data. They examined the importance of the initial diagnosis in patients with both STS and lymphoma, in addition to determining the role of radiation therapy, a known inducer of sarcoma.RESULTS:Review of their sarcoma, gastric, urology, breast, and gynecology databases revealed that lymphoma (95%) or leukemia (5%) occurred in 1.6% of STS patients in comparison to 0.5% of patients in the other databases (P < .01; odds ratio, 3.1; 95% confidence interval, 2.6‐3.8). Patients diagnosed with STS only were more likely to die of disease at 10 years compared with those with STS and lymphoma (P = .006), but this difference was not significant when patients presenting with recurrence or metastases were excluded. Among patients with lymphoma and STS, lymphoma was the first diagnosis in 71% of patients. Median survival after STS diagnosis was shorter when lymphoma was the initial diagnosis (67 vs 170 months, P = .002), and these patients were more likely to have radiation‐associated STS (44% vs 3%, P < .001).CONCLUSIONS:There was a 3‐fold higher incidence of lymphoma in STS patients compared with other solid tumors. The poor prognosis of those diagnosed with both STS and lymphoma was most likely a consequence of prior irradiation. Cancer 2011. © 2011 American Cancer Society.
Using myc genes to search for stem cells in the ciliary margin of the Xenopus retina
Authors: Xue Xiao Yan , Harris William A. 
Published: April 2011

AbstractThe ciliary marginal zone (CMZ) of fish and frog retinas contains cells that proliferate throughout postembryonic development as the retina grows with increasing body size, indicating the presence of stem cells in this region. However, neither the location nor the molecular identity of retinal stem cells has been identified. Here, we show in Xenopus that c‐myc and n‐myc are sequentially expressed both during development and in the post‐embryonic retina. The c‐myc+/n‐myc− cells near the extreme periphery of the CMZ cycle more slowly and preferentially retain DNA label compared to their more central cmyc+/n‐myc+ neighbors which cycle rapidly and preferentially dilute DNA label. During retinal development c‐myc is functionally required earlier than n‐myc, and n‐myc expression depends on earlier c‐myc expression. The expression of c‐myc but not n‐myc in the CMZ depends on growth factor signaling. Our results suggest that c‐myc+/n‐myc− cells in the far peripheral CMZ are candidates for a niche‐dependent population of retinal stem cells that give rise to more centrally located and rapidly dividing n‐myc+ progenitors of more limited proliferative potential. Analysis of homologues of these genes in the zebrafish CMZ suggests that the transition from c‐myc to n‐myc expression might be conserved in other lower vertebrates whose retinas growth throughout life. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 475–490, 2012
Zebrafish as a genomics model for human neurological and polygenic disorders
Authors: Becker Thomas S. , Rinkwitz Silke 
Published: April 2011

AbstractWhole exome sequencing and, to a lesser extent, genome‐wide association studies, have provided unprecedented advances in identifying genes and candidate genomic regions involved in the development of human disease. Further progress will come from sequencing the entire genome of multiple patients and normal controls to evaluate overall mutational burden and disease risk. A major challenge will be the interpretation of the resulting data and distinguishing true pathogenic mutations from rare benign variants. While in model organisms such as the zebrafish, mutants are sought that disrupt the function of individual genes, human mutations that cause, or are associated with, the development of disease, are often not acting in a Mendelian fashion, are frequently of small effect size, are late onset, and may reside in noncoding parts of the genome. The zebrafish model is uniquely poised for understanding human coding‐ and noncoding variants because of its sequenced genome, a large body of knowledge on gene expression and function, rapid generation time, and easy access to embryos. A critical advantage is the ease of zebrafish transgenesis, both for the testing of human regulatory DNA driving expression of fluorescent reporter proteins, and the expression of mutated disease‐associated human proteins in specific neurons to rapidly model aspects of neurological disorders. The zebrafish affords progress both through its model genome and it is rapidly developing transparent model vertebrate embryo. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 415–428, 2012
Detection of isoform‐specific fibroblast growth factor receptors by whole‐mount in situ hybridization in early chick embryos
Authors: Nishita Junko , Ohta Sho , Bleyl Steven B. , Schoenwolf Gary C. 
Published: April 2011

AbstractWe have developed “b” and “c” isoform‐specific chicken fibroblast growth factor (FGF) receptor 1–3 probes for in situ hybridization. We rigorously demonstrate the specificity of these probes by using both dot blot hybridization and whole‐mount in situ hybridization during neurulation and early postneurulation stages, and we compare expression patterns of each of the three isoform‐specific probes to one another and to generic probes to each of the three (non–isoform‐specific) FGF receptors. We show that the expression pattern of each receptor is represented by the collective expression of each of its two isoforms, with the expression of each FGF receptor being most similar to that of its “c” isoform at two of the three stages studied, and that tissue and stage differences exist in the patterns of expression of the six isoforms. We demonstrate the usefulness of these probes for defining the differential tissue expression of FGF receptor 1–3 isoforms. Developmental Dynamics 240:1537–1547, 2011. © 2011 Wiley‐Liss, Inc.
The chicken polydactyly (Po) locus causes allelic imbalance and ectopic expression of Shh during limb development
Authors: Dunn Ian C. , Paton I. Robert , Clelland Allyson K. , Sebastian Sujith , Johnson Edward J. , McTeir Lynn , Windsor Dawn , Sherman Adrian , Sang Helen , Burt Dave W. , Tickle Cheryll , Davey Megan G. 
Published: April 2011

AbstractPoint mutations in the intronic ZRS region of Lmbr1, a limb specific cis‐regulatory element of Sonic hedgehog (Shh), are associated with polydactyly in humans, cats, and mice. We and others have recently mapped the dominant preaxial polydactyly (Po) locus in Silkie chickens to a single nucleotide polymorphism (SNP) in the ZRS region. Using polymorphisms in the chicken Shh sequence, we confirm that the ZRS region directly regulates Shh expression in the developing limb causing ectopic Shh expression in the anterior leg, prolonged Shh expression in the posterior limb, and allelic imbalance between wt and Slk Shh alleles in heterozygote limbs. Using Silkie legs, we have explored the consequences of increased Shh expression in the posterior leg on the patterning of the toes, and the induction of preaxial polydactyly. Developmental Dynamics 240:1163–1172, 2011. © 2011 Wiley‐Liss, Inc.
Non‐canonical wnt signals antagonize and canonical wnt signals promote cell proliferation in early kidney development
Authors: McCoy Kyle E. , Zhou Xiaolan , Vize Peter D. 
Published: April 2011

AbstractCanonical and non‐canonical wnt signals often have opposed roles. In this report, we use developing Xenopus embryos to demonstrate a novel anti‐proliferative role for non‐canonical wnt signals in the very earliest stages of kidney development. Non‐canonical wnt signals were down‐regulated using PDZ domain mutants of dishevelled 2 and up‐regulated using wild‐type vang‐like 2, while canonical signals were manipulated using dominant‐negative forms of lef1 or treatment with lithium. When non‐canonical signals are down‐regulated in the developing Xenopus pronephros, cell proliferation rates increased and when canonical signals were shutdown the opposite occurred. Treatment with lithium chloride has a powerful pro‐proliferative effect on the forming nephric primordium. Together these data show that in addition to previously documented antagonisms between these distinct wnt signaling pathways, they also have opposing effects on cell division. Developmental Dynamics 240:1558–1566, 2011. © 2011 Wiley‐Liss, Inc.
Pleiotropic patterning response to activation of Shh signaling in the limb apical ectodermal ridge
Authors: Wang Chi‐Kuang Leo , Tsugane Mizuyo H. , Scranton Victoria , Kosher Robert A. , Pierro Louis J. , Upholt William B. , Dealy Caroline N. 
Published: April 2011

AbstractSonic hedgehog (Shh) signaling in the limb plays a central role in coordination of limb patterning and outgrowth. Shh expression in the limb is limited to the cells of the zone of polarizing activity (ZPA), located in posterior limb bud mesoderm. Shh is not expressed by limb ectoderm or apical ectodermal ridge (AER), but recent studies suggest a role for AER–Shh signaling in limb patterning. Here, we have examined the effects of activation of Shh signaling in the AER. We find that targeted expression of Shh in the AER activates constitutive Shh signaling throughout the AER and subjacent limb mesoderm, and causes a range of limb patterning defects with progressive severity from mild polydactyly, to polysyndactyly with proximal defects, to severe oligodactyly with phocomelia and partial limb ventralization. Our studies emphasize the importance of control of the timing, level and location of Shh pathway signaling for limb anterior–posterior, proximal–distal, and dorsal–ventral patterning. Developmental Dynamics 240:1289–1302, 2011. © 2011 Wiley‐Liss, Inc.
Development of the external genitalia: Conserved and divergent mechanisms of appendage patterning
Authors: Cohn Martin J. 
Published: April 2011

AbstractOver the past decade, the genetics of external genital development have begun to be understood. Male and female external genitalia develop from the genital tubercle. The early tubercle has a superficial resemblance to the limb bud, but an important distinction is that the limb consists of only mesoderm and ectoderm, whereas the genital tubercle also has an endodermal component, the urethral epithelium. Urethral epithelium, which expresses Sonic hedgehog, acts as a signaling region that controls outgrowth and pattern formation, and ultimately differentiates into the urethral tube. While there are intriguing parallels between limb and genital development, recent studies have identified some key differences, including the role of Fgf signaling. Our understanding of the mechanisms of genital development still lags far behind the limb, and major questions remain to be answered, including the molecular nature of the signals that initiate genital budding, sustain outgrowth, induce tissue polarity and orchestrate urethral tubulogenesis. Developmental Dynamics 240:1108–1115, 2011. © 2011 Wiley‐Liss, Inc.
Guided self‐help as the first step for bulimic symptoms: Implementation of a stepped‐care model within specialized psychiatry
Authors: Ramklint Mia , Jeansson Mats , Holmgren Sven , Ghaderi Ata 
Published: April 2011

AbstractObjective:This study describes the implementation and effectiveness of the first step, guided self‐help (GSH), in a clinical setting, of a stepped‐care model of cognitive behavior therapy for patients with bulimic symptoms.Method:Eighty‐nine patients participated.Results:In the intent to‐treat analyses, the effect sizes were small to moderate (0.25–0.66). However, the effect sizes were substantially larger (0.44–1.66) for the patients who completed all the GSH sessions (45%). The majority of noncompleters stayed within psychiatric services. Supplementary treatments were mostly directed towards comorbid conditions, especially depression. Those discontinuing treatment in advance where characterized by more lifetime diagnoses and higher ratings on the restraint subscale of the EDE‐Q.Discussion:GSH within specialized psychiatry might be effective for about 30% of the patients. There is no indication of patients losing their confidence in psychiatric services by being offered GSH as the first treatment. © 2011 by Wiley Periodicals, Inc. (Int J Eat Disord 2012)
Synthesis and Luminescent Properties of Cerium‐, Terbium‐, or Dysprosium‐Doped Gd4Si2O7N2 Materials
Authors: Song Yanhua , Guo Ning , You Hongpeng 
Published: April 2011

AbstractGd4Si2O7N2, a new oxynitride, has been prepared and the luminescent properties of the Ce3+, Tb3+ or Dy3+ doped product have been studied. XRD results indicate that Gd4Si2O7N2 is isostructural with Tb4Si2N2O7 and belongs to the monoclinic system. The SEM image shows that the synthesized powder disperses well and the particle diameter is between 1.40–4.0 μm. Upon excitation at 350 nm, Gd4Si2O7N2:Ce3+ exhibits blue emission peaking at 445 nm, which may have potential application as a blue phosphor in the field of solid state lighting. The major mechanism for the concentration quenching of the Ce3+ emission in Gd4Si2O7N2:Ce3+ is dipole‐dipole interactions. The emission colour of Gd4Si2O7N2:Tb3+ can be tuned from blue to green by changing the Tb3+ concentration. The ratio of yellow to blue emission for Gd4Si2O7N2:Dy3+ grows higher with an increase in the Dy3+ concentration. Energy transfer from the Gd3+ ions to Tb3+ or Dy3+ ions in the Gd4Si2O7N2 host was also observed.
Enthalpy–Entropy Correlation for Hydrogen Adsorption on MOFs: Variable‐Temperature FTIR Study of Hydrogen Adsorption on MIL‐100(Cr) and MIL‐101(Cr) (Eur. J. Inorg. Chem. 11/2011)
Authors: Palomino Gemma Turnes , Cabello Carlos Palomino , Areán Carlos Otero 
Published: April 2011

AbstractThe cover picture shows an allegoric representation of the dawning hopes of a hydrogen energy transition, which would alleviate the foreseeable shortage of fossil fuels for the transportation sector. Metal‐organic frameworks (MOFs), represented by the honeycomb structure, have become a main focus in the current search for economically viable materials for hydrogen storage and delivery. The signpost at the left of the picture is a reminder that thermodynamics of the hydrogen uptake and delivery process is ruled by the corresponding enthalpy and entropy changes, which are shown to be interrelated. Both of these thermodynamic quantities have to be taken into account for intelligent design of hydrogen storage materials. Details are discussed in the article by C. O. Areán et al. on p. 1703 ff.
Diastereoselective Deprotonative Metalation of Sugar‐Derived Ferrocene Esters Using Mixed Lithium–Cadmium Combinations
Authors: Sreeshailam Aare , Dayaker Gandrath , Chevallier Floris , Roisnel Thierry , Krishna Palakodety Radha , Mongin Florence 
Published: April 2011

AbstractThe ability of a mixed lithium–cadmium amide to deproto‐metallate diastereoselectively several sugar‐derived ferrocene esters was studied. The ferrocenecarboxylates generated from α‐D‐glucofuranoses gave the best results, as evidenced after subsequent trapping with iodine. Good chemical yields and diastereoselectivities up to 82 % in favor of the SP stereoisomer were obtained. The use of a different chiral group favored the formation of the RP stereoisomer, isolated in 34 % yield and 98 % diastereoselectivity.
Autologistic models for binary data on a lattice
Authors: Hughes John , Haran Murali , Caragea Petruţa C. 
Published: April 2011

AbstractThe autologistic model is a Markov random field model for spatial binary data. Because it can account for both statistical dependence among the data and for the effects of potential covariates, the autologistic model is particularly suitable for problems in many fields, including ecology, where binary responses, indicating the presence or absence of a certain plant or animal species, are observed over a two‐dimensional lattice. We consider inference and computation for two models: the original autologistic model due to Besag, and the centered autologistic model proposed recently by Caragea and Kaiser. Parameter estimation and inference for these models is a notoriously difficult problem due to the complex form of the likelihood function. We study pseudolikelihood (PL), maximum likelihood (ML), and Bayesian approaches to inference and describe ways to optimize the efficiency of these algorithms and the perfect sampling algorithms upon which they depend, taking advantage of parallel computing when possible. We conduct a simulation study to investigate the effects of spatial dependence and lattice size on parameter inference, and find that inference for regression parameters in the centered model is reliable only for reasonably large lattices (n > 900) and no more than moderate spatial dependence. When the lattice is large enough, and the dependence small enough, to permit reliable inference, the three approaches perform comparably, and so we recommend the PL approach for its easier implementation and much faster execution. Copyright © 2011 John Wiley & Sons, Ltd.