bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of insulin on the soluble receptor for advanced glycation end products (RAGE)
Authors: Lam J. K. Y. , Wang Y. , Shiu S. W. M. , Wong Y. , Betteridge D. J. , Tan K. C. B. 
Published: February 2013

AbstractAimsThe receptor for advanced glycation end products (RAGE) plays an important role in the pathogenesis of diabetic complications. RAGE transcript splicing generates a number of isoforms, including a full‐length membrane‐bound receptor and a soluble isoform, endogenous secretory RAGE (esRAGE). Soluble forms of the receptor (sRAGE) can also be formed by ectodomain shedding of the membrane‐associated receptor. We have evaluated serum levels of sRAGE and esRAGE in Chinese patients with Type 1 diabetes and investigated the effect of insulin on the generation of esRAGE and sRAGE in vitro.MethodsSerum sRAGE and esRAGE were measured by ELISA. The in vitro effect of insulin was investigated by incubating THP‐1 macrophages with insulin and RAGE isoforms in cell lysate and conditioned media determined.ResultsIn patients with diabetes, both serum esRAGE and sRAGE were significantly higher than in age‐matched healthy subjects without diabetes. In vitro, insulin increased esRAGE and total RAGE isoform expression in cell lysate on a western blot, and reverse transcription–polymerase chain reaction showed an increase in esRAGE and full‐length RAGE mRNA. This was accompanied by an increase in esRAGE and sRAGE in cell conditioned media. Pretreatment of THP‐1 cells with a general metalloproteinase inhibitor GM6001 significantly reduced the production of sRAGE, suggesting that insulin also increased the cleavage of full‐length cell surface RAGE to form sRAGE.ConclusionsChinese patients with Type 1 diabetes have higher serum levels of esRAGE and sRAGE. In vitro, insulin not only increases both full‐length RAGE and esRAGE expression, but can also stimulate the shedding of sRAGE from the membrane‐bound receptor.
Perceived Barriers, Resources, and Training Needs of Rural Primary Care Providers Relevant to the Management of Childhood Obesity
Authors: Findholt Nancy E. , Davis Melinda M. , Michael Yvonne L. 
Published: February 2013

AbstractPurposeTo explore the perceived barriers, resources, and training needs of rural primary care providers in relation to implementing the American Medical Association Expert Committee recommendations for assessment, treatment, and prevention of childhood obesity.MethodsIn‐depth interviews were conducted with 13 rural primary care providers in Oregon. Transcribed interviews were thematically coded.ResultsBarriers to addressing childhood obesity fell into 5 categories: barriers related to the practice (time constraints, lack of reimbursement, few opportunities to detect obesity), the clinician (limited knowledge), the family/patient (family lifestyle and lack of parent motivation to change, low family income and lack of health insurance, sensitivity of the issue), the community (lack of pediatric subspecialists and multidisciplinary/tertiary care services, few community resources), and the broader sociocultural environment (sociocultural influences, high prevalence of childhood obesity). There were very few clinic and community resources to assist clinicians in addressing weight issues. Clinicians had received little previous training relevant to childhood obesity, and they expressed an interest in several topics.ConclusionsRural primary care providers face extensive barriers in relation to implementing recommended practices for assessment, treatment, and prevention of childhood obesity. Particularly problematic is the lack of local and regional resources. Employing nurses to provide case management and behavior counseling, group visits, and telehealth and other technological communications are strategies that could improve the management of childhood obesity in rural primary care settings.
Predation in Homogeneous and Heterogeneous Phage Environments Affects Virulence Determinants of Pseudomonas aeruginosa
Authors: Hosseinidoust Zeinab , Tufenkji Nathalie , van de Ven Theo G. M. 
Published: February 2013

ABSTRACT

The rise of bacterial variants in the presence of lytic phages has been one of the basic grounds for evolution studies. However, there are incongruent results among different studies investigating the effect of phage resistance acquisition on bacterial fitness and virulence. We used experimental evolution to generate three classes of
Pseudomonas aeruginosa
variants under selective pressure from two different homogeneous phage environments and one heterogeneous phage environment. The fitness and virulence determinants of the variants, such as growth, motility, biofilm formation, resistance to oxidative stress, and the production of siderophores and chromophores, changed significantly compared to the control. Variants with similar colony morphology that were developed through different phage treatments have different phenotypic traits. Also, mRNA transcription for genes associated with certain phenotypic traits changed significantly; however, sequencing did not reveal any point mutations in selected gene loci. Furthermore, the appearance of small colony variants and melanogenic variants and the increase in pyocyanin and pyoverdin production for some variants are believed to affect the virulence of the population. The knowledge gained from this study will fundamentally contribute to our understanding of the evolutionary dynamics of bacteria under phage selective pressure which is crucial to the efficient utilization of bacteriophages in medical contexts.
Structural Insights into Substrate Binding by
Pv
FKBP35, a Peptidylprolyl
cis-trans
Isomerase from the Human Malarial Parasite Plasmodium vivax
Authors: Alag Reema , Balakrishna Asha Manikkoth , Rajan Sreekanth , Qureshi Insaf A. , Shin Joon , Lescar Julien , Grüber Gerhard , Yoon Ho Sup 
Published: February 2013

ABSTRACT

The immunosuppressive drug FK506 binding proteins (FKBPs), an immunophilin family with the immunosuppressive drug FK506 binding property, exhibit peptidylprolyl
cis-trans
isomerase (PPIase) activity. While the cyclophilin-catalyzed peptidylprolyl isomerization of X-Pro peptide bonds has been extensively studied, the mechanism of the FKBP-mediated peptidylprolyl isomerization remains uncharacterized. Thus, to investigate the binding of FKBP with its substrate and the underlying catalytic mechanism of the FKBP-mediated proline isomerization, here we employed the FK506 binding domain (FKBD) of the human malarial parasite
Plasmodium vivax
FK506 binding protein 35 (
Pv
FKBP35) and examined the details of the molecular interaction between the isomerase and a peptide substrate. The crystallographic structures of apo
Pv
FKBD35 and its complex with the tetrapeptide substrate succinyl-Ala-Leu-Pro-Phe-
p
-nitroanilide (sALPFp) determined at 1.4 Å and 1.65 Å resolutions, respectively, showed that the substrate binds to
Pv
FKBD35 in a
cis
conformation. Nuclear magnetic resonance (NMR) studies demonstrated the chemical shift perturbations of D55, H67, V73, and I74 residues upon the substrate binding. In addition, the X-ray crystal structure, along with the mutational studies, shows that Y100 is a key residue for the catalytic activity. Taken together, our results provide insights into the catalytic mechanism of
Pv
FKBP35-mediated
cis-trans
isomerization of substrate and ultimately might aid designing substrate mimetic inhibitors targeting the malarial parasite FKBPs.
Epithelial-to-Mesenchymal Transition and Autophagy Induction in Breast Carcinoma Promote Escape from T-cell–Mediated Lysis
Authors: Akalay Intissar , Janji Bassam , Hasmim Meriem , Noman Muhammad Zaeem , André Fabrice , De Cremoux Patricia , Bertheau Philippe , Badoual Cécile , Vielh Philippe , Larsen Annette K. , Sabbah Michèle , Tan Tuan Zea , Keira Joan Herr , Ying Hung Nicole Tsang , Thiery Jean Paul , Mami-Chouaib Fathia , Chouaib Salem 
Published: February 2013

Abstract
Epithelial-to-mesenchymal transition (EMT) mediates cancer cell invasion, metastasis, and drug resistance, but its impact on immune surveillance has not been explored. In this study, we investigated the functional consequences of this mode of epithelial cell plasticity on targeted cell lysis by cytotoxic T lymphocytes (CTL). Acquisition of the EMT phenotype in various derivatives of MCF-7 human breast cancer cells was associated with dramatic morphologic changes and actin cytoskeleton remodeling, with CD24−/CD44+/ALDH+ stem cell populations present exhibiting a higher degree of EMT relative to parental cells. Strikingly, acquisition of this phenotype also associated with an inhibition of CTL-mediated tumor cell lysis. Resistant cells exhibited attenuation in the formation of an immunologic synapse with CTLs along with the induction of autophagy in the target cells. This response was critical for susceptibility to CTL-mediated lysis because siRNA-mediated silencing of beclin1 to inhibit autophagy in target cells restored their susceptibility to CTL-induced lysis. Our results argue that in addition to promoting invasion and metastasis EMT also profoundly alters the susceptibility of cancer cells to T-cell–mediated immune surveillance. Furthermore, they reveal EMT and autophagy as conceptual realms for immunotherapeutic strategies to block immune escape. Cancer Res; 73(8); 2418–27. ©2013 AACR.
A system-level, molecular evolutionary analysis of mammalian phototransduction
Authors: Invergo Brandon M , Montanucci Ludovica , Laayouni Hafid , Bertranpetit Jaume 
Published: February 2013

Abstract

Background
Visual perception is initiated in the photoreceptor cells of the retina via the phototransduction system. This system has shown marked evolution during mammalian divergence in such complex attributes as activation time and recovery time. We have performed a molecular evolutionary analysis of proteins involved in mammalian phototransduction in order to unravel how the action of natural selection has been distributed throughout the system to evolve such traits.

Results
We found selective pressures to be non-randomly distributed according to both a simple protein classification scheme and a protein-interaction network representation of the signaling pathway. Proteins which are topologically central in the signaling pathway, such as the G proteins, as well as retinoid cycle chaperones and proteins involved in photoreceptor cell-type determination, were found to be more constrained in their evolution. Proteins peripheral to the pathway, such as ion channels and exchangers, as well as the retinoid cycle enzymes, have experienced a relaxation of selective pressures. Furthermore, signals of positive selection were detected in two genes: the short-wave (blue) opsin (OPN1SW) in hominids and the rod-specific N
a
+/ C
a
2+, K
+ ion exchanger (SLC24A1) in rodents.

Conclusions
The functions of the proteins involved in phototransduction and the topology of the interactions between them have imposed non-random constraints on their evolution. Thus, in shaping or conserving system-level phototransduction traits, natural selection has targeted the underlying proteins in a concerted manner.
Synthesis of Six-membered Silacycles by Intramolecular Nucleophilic Substitution at Silicon Involving the Cleavage of Carbon–Silicon Bonds
Authors: Onoe Masahiro , Morioka Toshifumi , Tobisu Mamoru , Chatani Naoto 
Published: February 2013

Abstract
An intramolecular nucleophilic substitution at silicon using organolithium reagents via the cleavage of an inert carbon–silicon bond has been developed as a viable tool for the synthesis of six-membered silacycles.
Template-free Synthesis of Highly Porous Carbon Nitride, nanoC3N4
Authors: Iwamoto Tomoyuki , Masui Yoichi , Wang Jiacheng , Onaka Makoto 
Published: February 2013

Abstract
A novel template-free and postsynthetic preparation of a highly porous carbon nitride material, nanoC3N4, was developed using concentrated sulfuric acid as the dispersion medium, followed by impregnation with ethanol. nanoC3N4 has a structure similar to that of graphitic carbon nitride composed of melem polymers but has a stronger basicity.
Spirocyclisation of phytoalexin 1-methoxybrassinin in the presence of Grignard reagents
Authors: Očenáš Peter , Tomášová Lucia , Kutschy Peter , Pazdera Pavel , Mojžiš Ján , Pilátová Martina 
Published: February 2013

AbstractThe anti-cancer properties of naturally occurring (2R, 3R)-(−)-1-methoxyspirobrassinol methyl ether (I) and their synthetic amino or piperidyl analogues II inspired us to study the synthesis of new target compounds III with a C—C bond in the 2-position of indole rather than a C—N or C—O bond (I or II respectively). The goal was achieved via electrophilic-nucleophilic 3,2-difunctionalisation of 1-methoxybrassinin (IV) in the presence of bromine and the Grignard reagent leading to the formation of cis- and trans-C—C analogues of I. Finally, the anti-cancer activities of the new compounds were measured and compared with I and II in order to show the importance of a heteroatom in the 2-substituted indole on the anti-cancer activity of spirobrassinols.
Degradation and toxicity changes in aqueous solutions of chloroacetic acids by Fenton-like treatment using zero-valent iron
Authors: Mackuľak Tomáš , Prousek Josef , Smolinská Miroslava , Olejníková Petra , Takáčová Alžbeta , Drtil Miloslav 
Published: February 2013

AbstractThree priority pollutants, i.e. mono-, di-, and trichloroacetic acids, were degraded by the conventional Fenton AOP system (Fe2+ and H2O2). The results obtained suggest that the degradation decreased in the order: monochloroacetic, dichloroacetic, and trichloroacetic acid. The best of advanced oxidation processes (AOPs) for the degradation of trichloroacetic acid was reductive dechlorination with the use of zero-valent iron (Fe°). The results of Escherichia coli toxicity tests revealed that the reagents’ toxicity after the Fenton treatment process was decreased.
Family-Centered Principles Implemented in Home-Based, Clinic-Based, and School-Based Pediatric Settings
Authors: Fingerhut Patricia E. , Piro Jocelyn , Sutton Ashley , Campbell Rachel , Lewis Christy , Lawji Dilshad , Martinez Nicole 
Published: February 2013

AbstractOBJECTIVE: The goal of this study was to determine whether pediatric occupational therapy practitioners implemented family-centered principles in their practice.METHOD: Twenty-eight occupational therapy practitioners were interviewed in three practice settings: home based, clinic based, and school based. A grounded theory approach was used to analyze the results. Responses were compared across respondents and across practice settings.RESULTS: Responses varied among practitioners and, more significantly, practice settings. A continuum of family-centered practice was demonstrated, with home-based practice as the most family centered, school-based practice as the least family centered, and clinic practice varying in between.CONCLUSION: Occupational therapy practitioners are familiar with most principles of family-centered practice. However, implementation of those principles differs significantly across practice settings.
Ultrasound-Assisted Ion-Pair Dispersive Liquid–Liquid Microextraction of Trace Amounts of Lead in Water Samples Prior to Graphite Furnace Atomic Absorption Spectrometry Determination
Authors: Afzali Daryoush , Mohadesi Ali Reza , Falahnejad Masoumeh , Bahadori Behnoosh 
Published: February 2013

Abstract
A new ion-pair dispersive liquid–liquid microextraction method is described for separation and preconcentration of trace amounts of lead in different water samples. Graphite furnace atomic absorption spectrometry was used for determination of lead. The ion association complex between lead and iodide ions that forms is PbI4–2-tetradecyldimethylbenzylammonium, which is extracted into fine droplets of chlorobenzene. In order to reach the optimized experimental conditions, the influence of different parameters, such as concentration of KI, nature and volume of extraction solvents, pH effect, extraction time, and the period and speed of sonication and centrifugation, were optimized. The LOD was 0.08 ng/mL and the linear dynamic range was 0.20–8.0 ng/mL in initial solution with a correlation coefficient of 0.9985. Under the optimum conditions, the enrichment factor was 555.5. The proposed method was successfully applied for separation and determination of lead in sea, rain, river, and drinking water samples.
Simultaneous Determination of Danshensu, Salvianolic Acid B, and Paeonol in ShuangDan Oral Liquid by HPLC
Authors: Li Hua , Wang Siwang , Xie Yanhua , Zhang Bangle , Wang Jianbo , Yang Qian , Cao Wei 
Published: February 2013

Abstract
An HPLC-photodiode array detector (PDAD) method was developed for simultaneous determination of danshensu, salvianolic acid B, and paeonol in a traditional Chinese medicinal preparation ShuangDan oral liquid, which is widely used to treat coronary heart disease in China. The samples were separated on a SinoChrom ODS–BP C18 column with the column temperature maintained at 30°C. The mobile phase was composed of methanol and 2% (v/v) glacial acetic acid at a flow rate of 1.0 mL/min. The separation was finished within 30 min using linear gradient elution. All calibration curves showed good linearity (r &gt; 0.9997) within the test ranges. The method was simple, reliable, accurate, and specific. The intraday and interday precisions (RSD) were less than 0.85%. The recoveries were between 96.97 and 102.14%. The method was successfully applied to the determination of the three components in three commercial samples of ShuangDan oral liquid. The results indicated that the developed HPLC–PDAD assay could be readily utilized as a comprehensive quality control method for ShuangDan oral liquid.
Kinetics of Ethylene Oxide Desorption from Sterilized Materials
Authors: Mendes Gisela C , Brandão Teresa R S , Silva Cristina L M 
Published: February 2013

Abstract
Ethylene oxide gas is commonly used to sterilize medical devices, and concerns about using this agent on biological systems are well-established. Medical devices sterilized by ethylene oxide must be properly aerated to remove residual gas and by-products. In this work, kinetics of ethylene oxide desorption from different sterilized materials were studied in a range of aeration temperatures. The experimental data were well-described by a Fickian diffusion mass transfer behavior, and diffusivities were estimated for two textile and two polymeric materials within the temperature range of 1.5 to 59.0°C. The results will allow predictions of ethylene oxide desorption, which is a key step for the design of sterilization/aeration processes, contributing to an efficient removal of residual ethylene oxide content.
Method Development and Validation for Ultra-High Pressure Liquid Chromatography/Tandem Mass Spectrometry Determination of Multiple Prostanoids in Biological Samples
Authors: Yu Rui , Zhao Guiqing , Christman John W , Xiao Lei , van Breemen Richard B 
Published: February 2013

Abstract
Following oxygenation of arachidonic acid by cyclooxygenase to form prostaglandin H2 (PGH2), a variety of prostanoids can be generated with diverse physiologic effects on pain, inflammation, allergy, cardiovascular system, cancer, etc. To facilitate the quantitative analysis of prostanoids in human serum of cell culture, an ultra-high pressure LC (UHPLC)/MS/MS method was developed and validated for the measurement of six eicosanoids belonging to the cyclooxygenase pathway: PGE2, PGD2, 8-iso-PGF2α, PGF2α, 6-keto-PGF1α, and thromboxane B2 (TXB2 ). Selectivity, matrix effects, calibration model, precision, and accuracy (intraday and interday), lower limit of quantitation (LLOQ), recovery, stability, and sample dilution were evaluated. Fast UHPLC separation was carried out in only 0.5 min with isocratic elution, and each prostanoid was measured using negative electrospray ionization MS with collision-induced dissociation and selected reaction monitoring. UHPLC/MS/MS provided high throughput with peak widths of approximately 3 s and an LLOQ of 0.020 ng/mL for PGE2, 0.027 ng/mL for PGD2, 0.152 ng/mL for 8-iso-PGF2α, 0.179 ng/mL for PGF2α and 6-keto-PGF1α, and 0.013 ng/mL for TXB2.
Scaledown of Biopharmaceutical Purification Operations
Authors: Rathore Anurag S. , Joshi Varsha S. 
Published: February 2013

AbstractBiotech‐based therapeutics have emerged as the growth engine for the pharmaceutical industry. Successful development and commercialization of biotech processes require the understanding of the relationships between the various attributes of the product and the product's clinical safety and efficacy, as well as, the effect of the different process parameters on the product's attributes. The complexity of the biotech products and the requirement for rigorous experimentation justify working at small scales.This article presents general guidelines and relevant parameters affecting scale‐down of the various unit operations involved in purification of proteins. The key parameters, assessment methods, assessment techniques, and challenges involved in scale‐down are discussed.
Synthesis of 6‐Kestose using an Efficient β‐Fructofuranosidase Engineered by Directed Evolution
Authors: de Abreu Miguel , Alvaro‐Benito Miguel , Sanz‐Aparicio Julia , Plou Francisco J. , Fernandez‐Lobato Maria , Alcalde Miguel 
Published: February 2013

AbstractThe β‐fructofuranosidase (Ffase) from Schwanniomyces occidentalis (Ffase‐Leu196 variant) was subjected to four cycles of directed evolution to enhance the transglycosylation activity for the synthesis of β‐(2→6) linked fructooligosaccharides (FOS). With a 5.5‐fold improvement in fructose transferase activity over the parental type and greater selectivity for the synthesis of 6‐kestose (up to 73% of the total FOS), the mutants doubled FOS synthesis to 168 g L.−1 Whilst the F523V and H510P mutations were located at the C‐terminus of the protein, mutations Q78L and I203L were associated with the acidic catalytic triad where they modified its interactions with the surrounding residues, in turn varying the hydrolase and transferase rates.
Ruthenium‐Catalyzed Remote Electronic Activation of Aromatic CF Bonds
Authors: Watson Andrew J. A. , Atkinson Benjamin N. , Maxwell Aoife C. , Williams Jonathan M. J. 
Published: February 2013

AbstractThe tandem isomerization and nucleophilic aromatic substitution of allylic fluoro‐substituted benzylic alcohols is described for the first time. In the presence of the ruthenium complex Ru(PPh3)3(CO)(H)2, 1‐(4‐fluorophenyl)prop‐2‐en‐1‐ol is converted into the corresponding para‐amino ketone or para‐phenolic substituted ketone.
Mild Palladium‐Catalyzed Oxidative Direct ortho‐CH Acylation of Anilides under Aqueous Conditions
Authors: Szabó Fruzsina , Daru János , Simkó Dániel , Nagy Tibor Zs. , Stirling András , Novák Zoltán 
Published: February 2013

AbstractPalladium‐catalyzed cross‐dehydrogenative coupling between anilides and aromatic aldehydes was achieved under aqueous conditions. A wide variety of the desired benzophenone derivatives was isolated in good to excellent yield. The reaction rate acceleration effect of acid and detergent has been demonstrated. Mechanistic insight has been obtained from quantum chemical calculations.