bluuebunny/crossref_metadata_2025 huggingface dataset:
Extensive introgressive hybridization within the northern oriole group (Genus Icterus) revealed by three‐species isolation with migration analysis
Authors: Jacobsen Frode , Omland Kevin E.
Published: August 2012

Until recently, studies of divergence and gene flow among closely‐related taxa were generally limited to pairs of sister taxa. However, organisms frequently exchange genes with other non‐sister taxa. The “northern oriole” group within genus Icterus exemplifies this problem. This group involves the extensively studied hybrid zone between Baltimore oriole (Icterus galbula) and Bullock's oriole (I. bullockii), an alleged hybrid zone between I. bullockii and black‐backed oriole (I. abeillei), and likely mtDNA introgression between I. galbula and I. abeillei. Here, we examine the divergence population genetics of the entire northern oriole group using a multipopulation Isolation‐with‐Migration (IM) model. In accordance with Haldane's rule, nuclear loci introgress extensively beyond the I. galbula–I. bullockii hybrid zone, while mtDNA does not. We found no evidence of introgression between I. bullockii and I. abeillei or between I. galbula and I. abeillei when all three species were analyzed together in a three‐population model. However, traditional pairwise analysis suggested some nuclear introgression from I. abeillei into I. galbula, probably reflecting genetic contributions from I. bullockii unaccounted for in a two‐population model. Thus, only by including all members of this group in the analysis was it possible to rigorously estimate the level of gene flow among these three closely related species.
Phenotypic plasticity alone cannot explain climate‐induced change in avian migration timing
Authors: Van Buskirk Josh , Mulvihill Robert S. , Leberman Robert C.
Published: August 2012

Recent climate change has been linked to shifts in the timing of life‐cycle events in many organisms, but there is debate over the degree to which phenological changes are caused by evolved genetic responses of populations or by phenotypic plasticity of individuals. We estimated plasticity of spring arrival date in 27 species of bird that breed in the vicinity of an observatory in eastern North America. For 2441 individuals detected in multiple years, arrival occurred earlier during warm years, especially in species that migrate short distances. Phenotypic plasticity averaged −0.93 days °C−1 ± 0.70 (95% CI). However, plasticity accounted for only 13–25% of the climate‐induced trend in phenology observed over 46 years. Although our approach probably underestimates the full scope of plasticity, the data suggest that part of the response to environmental change has been caused by microevolution. The estimated evolutionary rates are plausible (0.016 haldanes).
Genetic ablation of PI3Kγ results in defective IL‐17RA signalling in T lymphocytes and increased IL‐17 levels
Authors: Harris Stephanie J. , Ciuclan Loredana , Finan Peter M. , Wymann Matthias P. , Walker Christoph , Westwick John , Ward Stephen G. , Thomas Matthew J.
Published: August 2012

The signalling molecule PI3Kγ has been reported to play a key role in the immune system and the inflammatory response. In particular, it facilitates the migration of haemato‐poietic cells to the site of inflammation. In this study, we reveal a novel role for PI3Kγ in the regulation of the pro‐inflammatory cytokine IL‐17. Loss of PI3Kγ or expression of a catalytically inactive mutant of PI3Kγ in mice led to increased IL‐17 production both in vitro and in vivo in response to various stimuli. The kinetic profile was unaltered from WT cells, with no effect on proliferation or other cytokines. Elevated levels of IL‐17 were not due to an aberrant expansion of IL‐17‐producing cells. Furthermore, we also identified an increase in IL‐17RA expression on PI3Kγ−/− CD4+ T cells, yet these cells exhibited impaired PI3K‐dependent signalling in response to IL‐17A, and subsequent NF‐κB phosphorylation. In vivo, instillation of recombinant IL‐17 into the airways of mice lacking PI3Kγ signalling also resulted in reduced phosphorylation of Akt. Cell influx in response to IL‐17 was also reduced in PI3Kγ−/− lungs. These data demonstrate PI3Kγ‐dependent signalling downstream of IL‐17RA, which plays a pivotal role in regulating IL‐17 production in T cells.
Increased red cell turnover in a line of CD22‐deficient mice is caused by Gpi1c: A model for hereditary haemolytic anaemia
Authors: Walker Jennifer A. , Hall Andrew M. , Kotsopoulou Ekaterini , Espeli Marion , Nitschke Lars , Barker Robert N. , Lyons Paul A. , Smith Kenneth G.C.
Published: August 2012

CD22, an inhibitory co‐receptor of the BCR, has been identified as a potential candidate gene for the development of autoimmune haemolytic anaemia in mice. In this study, we have examined Cd22tm1Msn CD22‐deficient mice and identified an increase in RBC turnover and stress erythropoiesis, which might be consistent with haemolysis. We then, however, eliminated CD22 deficiency as the cause of accelerated RBC turnover and established that enhanced RBC turnover occurs independently of B cells and anti‐RBC autoanti‐bodies. Accelerated RBC turnover in this particular strain of CD22‐deficient mice is red cell intrinsic and appears to be the consequence of a defective allele of glucose phosphate isomerase, Gpi1c. This form of Gpi1 was originally derived from wild mice and results in a substantial reduction in enzyme activity. We have identified the polymorphism that causes impaired catalytic activity in the Gpi1c allele, and biochemically confirmed an approximate 75% reduction of GPI1 activity in Cd22−/− RBCs. The Cd22−/−.Gpi1c congenic mouse provides a novel animal model of GPI1‐deficiency, which is one of the most common causes of chronic non‐spherocytic haemolytic anaemia in humans.
Nanoparticle‐Incorporated Functional Mesoporous Silica Colloid for Diverse Applications
Authors: Sinha Arjyabaran , Jana Nikhil R.
Published: August 2012

A generalized in situ synthesis approach has been developed to prepare primary‐amine‐terminated mesoporous silica particles incorporated with a wide range of nanoparticles in the size range 2–50 nm, such as quantum dots, iron oxide nanoparticles, doped semiconductor nanocrystals, and gold nanorods. The resultant mesoporous particles are 50–800 nm in size and have a primary‐amine‐terminated surface and different morphology such as isolated spheres, rods, wires, or covalently connected aggregates. These mesoporous particles can be transformed into different functional nanoparticles for diverse applications such as drug delivery, bioimaging, and water purification. Quantum dot incorporated mesoporous particles have been demonstrated as multifunctional drug delivery carriers with simultaneous use as imaging probes. Similarly, quantum dot/gold nanorod incorporated mesoporous particles have been used as cellular imaging probes and their cellular interaction/uptake have been enhanced after functionalization with oleyl or TAT peptide.
Evaluation of the Antibacterial Activity of Ag‐Loaded TiO2 Nanotubes
Authors: Roguska Agata , Belcarz Anna , Piersiak Tomasz , Pisarek Marcin , Ginalska Grażyna , Lewandowska Małgorzata
Published: August 2012

To date, studies of modified Ti surfaces for biomedical purposes have focused on observations of their morphology and on the identification of the physicochemical properties that influence their biological response. However, for implant materials, antibacterial properties are also of high importance. The use of metal and metal oxide nanoparticles as antimicrobial components of coatings is receiving particular attention. The aim of this work is to create nanoporous oxide layers on Ti with the addition of Ag nanoparticles in order to obtain coatings having both biocompatibility and antibacterial properties for biomedical applications. TiO2 nanotubes (NTs) were grown on a Ti substrate by electrochemical oxidation at constant voltage in a mixture of glycerol, deionized water, and NH4F. Silver particles of size 2–50 nm were deposited on the surface by the sputter deposition technique. The antimicrobial activities of titanium, TiO2‐NT, and Ag/TiO2‐NT surfaces were evaluated against four different bacterial strains prevalent in orthopedic infections: S. epidermidis, S. aureus, E. coli, and P. aeruginosa. Our results have shown that Ag nanoparticles can be incorporated into the biomaterial surface in a simple and economic manner suitable for the fabrication of new types of bactericidal materials. The presence of the TiO2‐NT layer significantly reduced the adhesion and biofilm formation of S. epidermidis cells on modified surfaces; the deposition of Ag nanoparticles enhanced the antiadhesive properties of the TiO2‐NT layer. Thus, these Ag/TiO2‐NT composite layers may be promising for combating post‐operative infection for applications in hard tissue replacement procedures.
Nano–Bio Interaction between Graphite Oxide Nanoparticles and Human Blood Components
Authors: Kim Hyoung‐Mi , Kim Kyoung‐Min , Lee Kyunghong , Kim Yoon Suk , Oh Jae‐Min
Published: August 2012

We investigated the effect of graphite oxide (GO) nanoparticles, which are an emerging nanomaterial with potential applications as drug‐delivery nanocarriers, on human blood cells and plasma proteins. Graphite oxides were successfully prepared by oxidizing graphite with potassium permanganate and sulfuric acid. Powder X‐ray diffraction patterns, FTIR, and Raman spectra show that the oxidation of graphite worked well and yielded GO nanolayers. To evaluate the interaction of GO with human blood components, we studied its hemolytic effect and protein binding kinetics. The nanoparticles did not show any significant hemolytic effect during 30 min at a very high concentration of 10 mg/mL, showing high compatibility with human blood. The interaction between GO nanoparticles and human blood cells was visualized with optical microscopy. Some nanoparticles were found at the periphery of blood cells, however, significant damages or morphological changes of blood cells upon exposure to nanoparticles were not detected. When we treated GO nanoparticles with plasma proteins, such as human serum albumin, γ‐immunoglobulin, and fibrinogen, they showed concentration‐dependent binding behavior, and the binding constant is comparable with other biocompatible nanoparticles.
Ruthenocenes and Half‐Open Ruthenocenes: Synthesis, Characterization, and Their Use as CVD Precursors for Ruthenium Thin Film Deposition
Authors: Tuchscherer André , Georgi Colin , Roth Nina , Schaarschmidt Dieter , Rüffer Tobias , Waechtler Thomas , Schulz Stefan E. , Oswald Steffen , Gessner Thomas , Lang Heinrich
Published: August 2012

Consecutive synthesis methodologies for the preparation of a series of trimethylsilyl and tert‐butyl‐substituted ruthenocenes of the type Ru(η5‐C5H3R1R2)(η5‐C5H3R3R4) (2, R1 = SiMe3, R2 = R3 = R4 = H; 3, R1 = R3 = SiMe3, R2 = R4 = H; 4, R1 = R2 = R3 = SiMe3, R4 = H; 5, R1 = R2 = R3 = R4 = SiMe3; 6, R1 = R3 = tBu, R2 = R4 = H; 7, R1 = R3 = tBu, R2 = SiMe3, R4 = H; 8, R1 = R3 = tBu, R2 = R4 = SiMe3) and Ru(η5‐2,3‐Me2C5H5)(η5‐C5H4R) (10, R = tBu; 12, R = SiMe3) are discussed and their use as a MOCVD precursor for the deposition of ruthenium is reported. The molecular structures of 3, 5–8, 10, and 12 in the solid state are reported. The half‐open ruthenocenes 10 and 12, which are liquids at ambient temperature, exhibit significantly shorter Ru–centroid (η5‐2,3‐Me2C5H5) bond lengths in contrast to ruthenocenes 3 and 5–8. The thermal behavior of all ruthenocenes was studied by thermogravimetric analysis showing that they evaporate without decomposition at atmospheric pressure. In addition, vapor pressure measurements were carried out to obtain profound information about the volatility of the synthesized sandwich compounds. The highest vapor pressures were found for 10 and 12. It was observed that the higher the number of SiMe3 groups, the higher the deposition temperature. All compounds were applied as precursors in MOCVD. The depositions on Si/SiO2 targets were carried out in a vertical cold‐wall CVD reactor between 633 and 688 K with a flow rate of 50 mL min–1 using nitrogen as the carrier gas and oxygen as the coreactant (50 mL min–1). With the tBu‐functionalized ruthenocenes 6 and 10 ruthenium thin films were obtained, while mixed ruthenium/SiO2 layers were formed with 2, 7, 8, and 12. The appropriate layers possess thicknesses between 75–135 nm and are conformal and dense as proven by SEM, EDX spectroscopy, and XPS studies.
Turning On Fluorescence with Thiols – Synthetic and Computational Studies on Diaminoterephthalates and Monitoring the Switch of the Ca2+ Sensor Recoverin
Authors: Wache Nina , Scholten Alexander , Klüner Thorsten , Koch Karl‐Wilhelm , Christoffers Jens
Published: August 2012

The fluorescence of maleimide‐functionalized diaminoterephthalate derivatives (NiWa Orange) is “turned on” by the conjugate addition of thiols. Three new representatives of this class of dyes with emission at 560 nm were synthesized from succinyl succinates. The mechanism of turning on the fluorescence was investigated by computational studies. Radiationless transition to an energetically low‐lying excited state by a nonadiabatic interaction was the mechanism leading to absence of fluorescence prior to the reaction of the probe with its molecular target. This concept was proven by labeling cysteine‐containing peptides and proteins. For example, the single cysteine residue at position 39 of the neuronal calcium sensor protein recoverin binds to NiWa Orange and turns on its fluorescence. The Ca2+‐dependent Förster resonance energy transfer (FRET) process from a tryptophan residue in proximity to Cys39‐bound NiWa Orange was used for the determination of differences in Ca2+‐binding affinities of myristoylated and nonmyristoylated recoverin.
Design and fabrication of a COP‐based microfluidic chip: Chronoamperometric detection of Troponin T
Authors: Abad Llibertat , Javier del Campo Francisco , Muñoz Francesc Xavier , Fernández Luis J. , Calavia Daniel , Colom Gloria , Salvador Juan P. , Marco María Pilar , Escamilla‐Gómez Vanessa , Esteban‐Fernández de Ávila Berta , Campuzano Susana , Pedrero María , Pingarrón José M. , Godino Neus , Gorkin Robert , Ducrée Jens
Published: August 2012

This work demonstrates the design and fabrication of an all cyclo‐olefin polymer based microfluidic device capable of capturing magnetic beads and performing electrochemical detection in a series of gold electrodes. The size of chip is of a microscope slide and features six independent measuring cells for multianalyte detection purposes. The aim of this work is to show that rapid prototyping techniques can be instrumental in the development of novel bioassays, particularly in clinical diagnosis applications. We show the successful determination of troponin‐T, a cardiac disease marker, in the clinically relevant range of 0.05–1.0 ng/mL. This methodology achieves a detection limit of 0.017 ng/mL in PBS solutions, and is capable of detecting less than 1 ng/mL in a 1:50 human serum dilution.
Effect of PVP on the electroosmotic mobility of wet‐etched glass microchannels
Authors: Milanova Denitsa , Chambers Robert D. , Bahga Supreet S. , Santiago Juan G.
Published: August 2012

We present an experimental study on the effect of polymer PVP on EOF mobility of microchannels wet etched into optical white soda lime glass, also known as Crown glass. We performed experiments to evaluate the effect of PVP concentration and pH on EOF mobility. We used on‐chip capillary zone electrophoresis and a neutral fluorescent dye as a passive marker to quantify the electroosmotic flow. We performed experiments under controlled conditions by varying pH from 5.2 and 10.3 and concentration of PVP from 0 to 2.0% w/w at constant ionic strength (30 mM). Our experiments show that PVP at concentrations of 1.0% or above very effectively suppress EOF at low pH (6.6). At high pH of 10.3, PVP has a much weaker suppressing effect on EOF and increasing its concentration above about 0.5% showed negligible effect on EOF mobility. Finally, we briefly discuss the effects of pH on using PVP as an adsorbed coating. Our experiments provide useful guidelines on choosing correct pH and concentration of PVP for effective EOF suppression in glass channels.
High order interactions of xenobiotic metabolizing genes and P53 codon 72 polymorphisms in acute leukemia
Authors: Chauhan Pradeep Singh , Ihsan Rakhshan , Mishra Ashwani Kumar , Yadav Dhirendra Singh , Saluja Sumita , Mittal Vishakha , Saxena Sunita , Kapur Sujala
Published: August 2012

Polymorphisms in xenobiotic metabolizing genes are associated with altered metabolism of carcinogens in acute leukemia (AL). This study applied two data mining approaches to explore potential interactions among P53 and xenobiotic metabolizing genes in 230 AL patients [131 acute myeloid leukemia (AML) and 99 acute lymphoblastic leukemia (ALL)] and 199 controls. Individually, none of the genotypes showed significant associations with AML risk. However, in ALL the CYP1A12A TC genotype was associated with increased risk (OR = 2.02; 95% CI = 1.14–3.58; P = 0.01), whereas the GSTM1 null genotype imparted reduced risk (OR = 0.55; 95% CI = 0.31–0.96; P = 0.03). In classification and regression tree analysis, combinations of GSTM1 present, CYP1A12C AA or GG, EPHX1 exon3 TC, and EPHX1 exon4 AA or GG genotype strongly enhanced the risk of AML (OR = 5.89; 95% CI = 1.40–26.62; P = 0.01). In ALL, combinations of CYP1A12A TT, P53 GG or CC and GSTP1 AG genotypes conferred the highest risk (OR = 4.19; 95% CI = 1.45–12.25; P = 0.004). In multifactor dimensionality reduction analysis, a four locus model (GSTP1, P53, EPHX1 exon3, and CYP1A12A) was the best predictor model for ALL risk. The association between this model and ALL risk remained true even at low prior probabilities of 0.01% (false positive report probability = 0.05). Interaction entropy interpretations of the best model of ALL revealed that two‐way interactions were mostly synergistic. These results suggest that high order gene–gene interactions play an important role in AL risk. Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.
An immersed boundary method wall model for high‐Reynolds‐number channel flow over complex topography
Authors: Anderson William
Published: August 2012

High‐Reynolds‐number channel flows regularly encounter topographies composed of multiple length scales and that protrude into the boundary layer. Physically, the presence of immersed obstacles leads to increased velocity gradients, turbulence production, and manifestation of wakes. Considerable challenges are associated with numerically describing the presence of obstacles in channel flows. Common approaches include generation of a computational mesh that is uniquely designed for the flow and obstacle, the immersed boundary method, and terrain‐following coordinates. There are challenges and limitations associated with each of these techniques. Specification of boundary conditions representing the perimeter of solid obstacles is a primary challenge of the immersed boundary method. In this document, a simplistic canopy stress‐like wall model is used to impose boundary conditions. The model isolates aerodynamically relevant local frontal areas through evaluation of the gradient of the topographic height field. The gradient of the height field describes both the surface‐normal direction and the frontal area, making it ideal for detecting areas on which the flow impinges. The model is tested in numerical simulations of turbulent half‐channel flow over topographies with different obstacles affixed–right prisms, rectangular prisms, ellipsoidal mounds, and sinusoids. In all cases, the performance is strong relative to datasets presented in the literature. Results are finally presented for numerical simulation of flow over complex synthetic fractal‐like topography and a synthetic city. These results show interesting trends in how the turbulent multiscale flow field responds to multiscale topography. Copyright © 2012 John Wiley & Sons, Ltd.
Genotype Imputation of MetabochipSNPs Using a Study‐Specific Reference Panel of ∼4,000 Haplotypes in African Americans From the Women's Health Initiative
Authors: Liu Eric Yi , Buyske Steven , Aragaki Aaron K. , Peters Ulrike , Boerwinkle Eric , Carlson Chris , Carty Cara , Crawford Dana C. , Haessler Jeff , Hindorff Lucia A. , Marchand Loic Le , Manolio Teri A. , Matise Tara , Wang Wei , Kooperberg Charles , North Kari E. , Li Yun
Published: August 2012

Genetic imputation has become standard practice in modern genetic studies. However, several important issues have not been adequately addressed including the utility of study‐specific reference, performance in admixed populations, and quality for less common (minor allele frequency [MAF] 0.005–0.05) and rare (MAF < 0.005) variants. These issues only recently became addressable with genome‐wide association studies (GWAS) follow‐up studies using dense genotyping or sequencing in large samples of non‐European individuals. In this work, we constructed a study‐specific reference panel of 3,924 haplotypes using African Americans in the Women's Health Initiative (WHI) genotyped on both the Metabochip and the Affymetrix 6.0 GWAS platform. We used this reference panel to impute into 6,459 WHI SNP Health Association Resource (SHARe) study subjects with only GWAS genotypes. Our analysis confirmed the imputation quality metric Rsq (estimated r2, specific to each SNP) as an effective post‐imputation filter. We recommend different Rsq thresholds for different MAF categories such that the average (across SNPs) Rsq is above the desired dosage r2 (squared Pearson correlation between imputed and experimental genotypes). With a desired dosage r2 of 80%, 99.9% (97.5%, 83.6%, 52.0%, 20.5%) of SNPs with MAF > 0.05 (0.03–0.05, 0.01–0.03, 0.005–0.01, and 0.001–0.005) passed the post‐imputation filter. The average dosage r2 for these SNPs is 94.7%, 92.1%, 89.0%, 83.1%, and 79.7%, respectively. These results suggest that for African Americans imputation of Metabochip SNPs from GWAS data, including low frequency SNPs with MAF 0.005–0.05, is feasible and worthwhile for power increase in downstream association analysis provided a sizable reference panel is available.
Bootstrap Aggregating of Alternating Decision Trees to Detect Sets of SNPs That Associate With Disease
Authors: Guy Richard T. , Santago Peter , Langefeld Carl D.
Published: August 2012

Complex genetic disorders are a result of a combination of genetic and nongenetic factors, all potentially interacting. Machine learning methods hold the potential to identify multilocus and environmental associations thought to drive complex genetic traits. Decision trees, a popular machine learning technique, offer a computationally low complexity algorithm capable of detecting associated sets of single nucleotide polymorphisms (SNPs) of arbitrary size, including modern genome‐wide SNP scans. However, interpretation of the importance of an individual SNP within these trees can present challenges. We present a new decision tree algorithm denoted as Bagged Alternating Decision Trees (BADTrees) that is based on identifying common structural elements in a bootstrapped set of Alternating Decision Trees (ADTrees). The algorithm is order , where n is the number of SNPs considered and k is the number of SNPs in the tree constructed. Our simulation study suggests that BADTrees have higher power and lower type I error rates than ADTrees alone and comparable power with lower type I error rates compared to logistic regression. We illustrate the application of these data using simulated data as well as from the Lupus Large Association Study 1 (7,822 SNPs in 3,548 individuals). Our results suggest that BADTrees hold promise as a low computational order algorithm for detecting complex combinations of SNP and environmental factors associated with disease.
Validation of terminal peptide of procollagen III for the detection and assessment of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease
Authors: Tanwar Sudeep , Trembling Paul M. , Guha Indra N. , Parkes Julie , Kaye Philip , Burt Alastair D. , Ryder Stephen D. , Aithal Guruprasad P. , Day Christopher P. , Rosenberg William M.
Published: August 2012

Liver biopsy is the reference standard for the detection of nonalcoholic steatohepatitis (NASH) within nonalcoholic fatty liver disease (NAFLD). The aim of this study was to identify a biomarker of NASH in patients without significant fibrosis. In all, 172 patients from two centers with biopsy-proven NAFLD were included in this study. Eighty-four patients from a single center were included as a derivation cohort and 88 patients from a second center were included as a validation cohort. Serum samples were tested for candidate markers of fibrosis and inflammation alongside hematological and biochemical markers. Among patients without advanced fibrosis, terminal peptide of procollagen III (PIIINP) was the only marker found to be associated with a histological diagnosis of NASH in both cohorts. PIIINP also correlated with the total NAFLD activity score (NAS) and its constituent components (P < 0.001). Area under receiver operating characteristic curve (AUROC) for PIIINP in discriminating between NASH and simple steatosis (SS) was 0.77-0.82 in patients with F0-2 fibrosis and 0.82-0.84 in patients with F0-3 fibrosis. PIIINP was elevated in patients with advanced fibrosis, the overwhelming majority of whom had NASH. When incorporating patients with all degrees of fibrosis from both cohorts, PIIINP was able to discriminate between patients with SS and those with NASH or advanced fibrosis with AUROC 0.85-0.87. Conclusion: PIIINP discriminates between SS and NASH or advanced fibrosis. The use of a single biomarker in this context will be of clinical utility in detecting the minority of patients with NAFLD who have NASH or advanced fibrosis related to NASH. (Hepatology 2013)
Endocrine and metabolic regulation of renal drug transporters
Authors: Yacovino Lindsay L. , Aleksunes Lauren M.
Published: August 2012

Renal xenobiotic transporters are important determinants of urinary secretion and reabsorption of chemicals. In addition to glomerular filtration, these processes are key to the overall renal clearance of a diverse array of drugs and toxins. Alterations in kidney transporter levels and function can influence the efficacy and toxicity of chemicals. Studies in experimental animals have revealed distinct patterns of renal transporter expression in response to sex hormones, pregnancy, and growth hormone. Likewise, a number of disease states including diabetes, obesity, and cholestasis alter the expression of kidney transporters. The goal of this review is to provide an overview of the major xenobiotic transporters expressed in the kidneys and an understanding of metabolic conditions and hormonal factors that regulate their expression and function. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:407–421, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21435
Unitals Admitting All Translations
Authors: Grundhöfer Theo , Stroppel Markus , Van Maldeghem Hendrik
Published: August 2012

Among all 2‐‐designs, we characterize the Hermitian unitals by the existence of sufficiently many translations. In arbitrary 2‐‐designs, each group of translations with given center acts semiregularly on the set of points different from the center.
Short noncoding DNA fragment improve efficiencies of in vivo electroporation‐mediated gene transfer
Authors: Peng Jinliang , Zhao Yonggang , Mai Junhua , Guo Wei , Xu Yuhong
Published: August 2012

Background

A major obstacle to the application of gene therapy methods in experimental and clinical practice is the lack of safe and efficient gene delivery systems. Electroporation has been shown to an effective physical delivery method. A variety of factors have been shown to affect the electroporation‐mediated gene delivery efficiency. In the present study, we assessed the usefulness of noncoding short‐fragment DNA (sf‐DNA) for facilitating electroporation‐mediated gene transfer.

Methods

The plasmid pGL3‐control encoding firefly luciferase was injected into tissues together with or without sf‐DNA. Immediately after injection, the tissues were electroporated and the level of luciferase activity was assessed 24 h later. Different types of DNA fragments with different molecular weights, structures and doses were compared. The transfection efficiencies of sf‐DNA‐mediated electroporation in different tissues or with different electric field strengths were examined.

Results

Plasmid DNA formulated with 300‐bp sf‐DNA resulted in a significant improvement in electroporation‐mediated gene transfer efficiency. The effect is dose‐dependent and is also affected by DNA fragment length and structure. It was useful for intramuscular electroporation application, as well as intratumoral application with various pulse voltage parameters.

Conclusions

The data obtained in the present study indicate that sf‐DNA can be used as a helper molecule to improve electroporation‐mediated gene transfection efficiency. Copyright © 2012 John Wiley & Sons, Ltd.
An efficient synthesis of isotope‐labeled PD0331179 and its labeled metabolite
Authors: Zhang Yinsheng
Published: August 2012

4‐[1‐Methyl‐2,4‐dioxo‐6‐(3‐phenyl‐prop‐1‐ynyl)‐1,4‐dihydro‐2H‐quinazolin‐3‐ylmethyl]‐benzoic acid, PD0331179, was under investigation as a matrix metalloproteinase‐13 inhibitor. 14C‐labeled and 2H‐labeled PD0331179 and its 2H‐labeled metabolite (PD0335699) were required to support its preclinical and clinical studies. [14C] 3‐phenyl‐1‐trimethyl/triphenylsilyl‐propyne was efficiently prepared starting with [14C] benzoic acid and used as a key‐labeled reagent for the synthesis of [14C] PD0331179. A one‐pot coupling reaction between aryl iodide and trialkylsilyl propyne was developed to make this synthesis more efficient. The details of these syntheses are reported. Copyright © 2012 John Wiley & Sons, Ltd.
The male copulatory system of european pea crabs (crustacea, brachyura, pinnotheridae)
Authors: Becker Carola , Türkay Michael , Brandis Dirk
Published: August 2012

The male copulatory system of the European pinnotherid species Pinnotheres pisum, Pinnotheres pectunculi, and Nepinnotheres pinnotheres was investigated by gross morphology, scanning electron microscopy, histological methods, and confocal laser scanning microscopy. The brachyuran copulatory system is consistently formed by paired penes and two pairs of abdominal appendages, the gonopods, functioning in sperm transfer. In pinnotherids, the long first gonopods transfer the sperm mass into the female ducts. The first gonopod has the ejaculatory canal inside that opens both basally and distally. The second gonopod is solid, short, and conical. During copulation, the penis and the second gonopod are inserted into the basal lumen of the first gonopod. While the penis injects the sperm mass, the second gonopod functions in the transport of spermatozoa inside the ejaculatory canal toward its distal opening. The second gonopod is adapted for the sealing of the tubular system in the first gonopod by its specific shape and the ability to swell. Longitudinal cuticle foldings of the second gonopod hook into structures inside the first gonopod. The second gonopod can interact with the penis during copulation by a flexible flap separating the lumina in which the second gonopod and the penis are inserted. J. Morphol., 2012. © 2012 Wiley Periodicals, Inc.
Dose–response effect of an intra‐tendon application of recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB) in a rat Achilles tendinopathy model
Authors: Shah Vivek , Bendele Alison , Dines Joshua S. , Kestler Hans K. , Hollinger Jeffrey O. , Chahine Nadeen O. , Hee Christopher K.
Published: August 2012

The purpose of this study was to assess whether intra‐tendon delivery of recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB) would improve Achilles tendon repair in a rat collagenase‐induced tendinopathy model. Seven days following collagenase induction of tendinopathy, one of four intra‐tendinous treatments was administered: (i) Vehicle control (sodium acetate buffer), (ii) 1.02 µg rhPDGF‐BB, (iii) 10.2 µg rhPDGF‐BB, or (iv) 102 µg rhPDGF‐BB. Treated tendons were assessed for histopathological (e.g., proliferation, tendon thickness, collagen fiber density/orientation) and biomechanical (e.g., maximum load‐to‐failure and stiffness) outcomes. By 7 days post‐treatment, there was a significant increase in cell proliferation with the 10.2 and 102 µg rhPDGF‐BB‐treated groups (p = 0.049 and 0.015, respectively) and in thickness at the tendon midsubstance in the 10.2 µg of rhPDGF‐BB group (p = 0.005), compared to controls. All groups had equivalent outcomes by Day 21. There was a dose‐dependent effect on the maximum load‐to‐failure, with no significant difference in the 1.02 and 102 µg rhPDGF‐BB doses but the 10.2 µg rhPDGF‐BB group had a significant increase in load‐to‐failure at 7 (p = 0.003) and 21 days (p = 0.019) compared to controls. The rhPDGF‐BB treatment resulted in a dose‐dependent, transient increase in cell proliferation and sustained improvement in biomechanical properties in a rat Achilles tendinopathy model, demonstrating the potential of rhPDGF‐BB treatment in a tendinopathy application. Consequently, in this model, data suggest that rhPDGF‐BB treatment is an effective therapy and thus, may be an option for clinical applications to treat tendinopathy. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 413–420, 2013
Iceberg‐type problems: Estimating Hidden parts of a continuum from the visible parts
Authors: Barnard Roger W. , Pearce Kent , Solynin Alexander Yu.
Published: August 2012

We consider the complex plane \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\mathbb {C}$\end{document} as a space filled by two different media, separated by the real axis \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\mathbb {R}$\end{document}. We define \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\mathbb {H}_+=\lbrace z: \,\Im \,z>0\rbrace$\end{document} to be the upper half‐plane. For a planar body E in \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\mathbb {C}$\end{document}, we discuss a problem of estimating characteristics of the “invisible” part, \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$E_-=E\setminus \mathbb {H}_+$\end{document}, from characteristics of the whole body E and its “visible” part, \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$E_+=E\cap \mathbb {H}_+$\end{document}. In this paper, we find the maximal draft of E as a function of the logarithmic capacity of E and the area of E+.
Metabolism and permeability of curcumin in cultured Caco‐2 cells
Authors: Dempe Julia S. , Scheerle Romy K. , Pfeiffer Erika , Metzler Manfred
Published: August 2012

Scope

Curcumin (CUR) and its major metabolite hexahydro‐CUR were studied in Caco‐2 cells and in the Caco‐2 Millicell® system in vitro to simulate their in vivo intestinal metabolism and absorption in humans.

Methods and results

Analysis of the incubation medium and cell lysate showed that Caco‐2 cells reduce CUR to hexahydro‐CUR and octahydro‐CUR, and conjugate CUR and its reductive metabolites with glucuronic acid and sulfate. Using the Caco‐2 Millicell® system, an efficient transfer of the conjugates into the basolateral, but not the apical, compartment was observed after apical administration. Likewise, hexahydro‐CUR was reduced to octahydro‐CUR, and glucuronide and sulfate conjugates almost exclusively permeated to the basolateral side. The apparent permeability coefficients (Papp values) of CUR, hexahydro‐CUR and their metabolites were determined and found to be extremely low for unchanged CUR, but somewhat higher for hexahydro‐CUR and the conjugated metabolites.

Conclusion

The results of this study clearly show that the systemic bioavailability of CUR from the intestine after oral intake must be expected to be virtually zero. Reductive and conjugated metabolites, formed from CUR in the intestine, exhibit moderate absorption. Thus, any biological effects elicited by CUR in tissues other than the gastrointestinal tract are likely due to CUR metabolites.
Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling, reduces energy efficiency and improves antioxidant and antiinflammatory defences in rats
Authors: Lionetti Lillà , Cavaliere Gina , Bergamo Paolo , Trinchese Giovanna , De Filippo Chiara , Gifuni Giorgio , Gaita Marcello , Pignalosa Angelica , Donizzetti Immacolata , Putti Rosalba , Di Palo Rossella , Barletta Antonio , Mollica Maria Pina
Published: August 2012

Dietary PUFA, mainly those of the n‐3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low‐fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso‐energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF‐α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione‐S‐transferase NADH quinone oxidoreductase) in DM‐treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid‐related factor 2 pathway.
Curcumin attenuates testicular damage, apoptotic germ cell death, and oxidative stress in streptozotocin‐induced diabetic rats
Authors: Kanter Mehmet , Aktas Cevat , Erboga Mustafa
Published: August 2012

Scope

The present study was designed to examine the protective and antioxidative effects of curcumin (Cur) on streptozotocin (STZ) induced testicular damage, apoptotic germ cell death, and oxidative stress.

Methods and results

Diabetes was induced by a single intraperitoneal injection of STZ (50 mg/kg). The rats in the Cur‐treated group were given Cur (100 mg/kg) once a day intragastrik for 8 weeks starting 3 days prior to STZ injection. Cur treatment significantly decreased the elevated tissue malondialdehyde levels and increased the reduced superoxide dismutase, and glutathione peroxidase enzyme activities in testis tissues samples. The Cur‐treated rats in the diabetic group showed an improved histological appearance and serum testosterone levels. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end‐labeling and there was a rise in the expression of proliferating cell nuclear antigen in testis tissues of Cur‐treated rats in the diabetic group.

Conclusion

These results demonstrate that Cur attenuated testicular damage in diabetic rats by decreasing oxidative stress.
Structural analyses of mannose pentasaccharide of high mannose type oligosaccharides by 1D and 2D NMR spectroscopy
Authors: Kubota Yumiko , Hori Hiroshi , Sawa Ryuichi , Seki Hiroko , Uzawa Jun
Published: August 2012

NMR spectroscopy is a very important and useful method for the structural analysis of oligosaccharides, despite its low sensitivity. We first applied conventional measuring methods, 2D DQF COSY, 1H–13C HSQC, and 1H–13C HMBC, and also the Double Pulsed Field Gradient Spin Echo (DPFGSE)‐TOCSY and DPFGSE‐NOESY/ROESY techniques to analyze a branched mannose pentasaccharide as a model of high mannose type N‐glycans in natural abundance. The NMR spectra of the model compound are very complex and difficult to analyze owing to overlapping signals. The superior selective irradiation capability of the DPFGSE technique is useful for fine structural and conformational analyses of such complex oligosaccharides.

We here introduce a novel technique called DPFGSE‐Double‐Selective Population Transfer (SPT)‐Difference and DPFGSE‐NOE/ROE‐SPT‐Difference spectroscopy. The DPFGSE‐Double‐SPT‐Difference method involves irradiation of two peaks from one proton and the subtraction of higher and lower peaks from each spectrum. The DPFGSE‐NOE/ROE‐SPT‐Difference method involves the transfer of the magnetization polarized by NOE/ROE from the nuclei to the spin‐coupled nuclei through scalar spin–spin interaction using the SPT method. Even if the signals in the NMR spectra overlap, each signal can be accurately assigned. In particular, DPFGSE‐NOE/ROE‐SPT‐Difference is very useful for identifying sugar connectivity. Copyright © 2012 John Wiley & Sons, Ltd.
NMR characterisation of structure in solvates and polymorphs of formoterol fumarate
Authors: Apperley David C. , Markwell A. Fraser , Harris Robin K. , Hodgkinson Paul
Published: August 2012

The solid‐state structures of two polymorphs and two alcoholates (ethanol and isopropanol) of formoterol fumarate have been investigated by a combination of NMR techniques. First‐principles shielding computations are combined with NMR data to successfully relate peaks to their crystallographic positions for the solvates, including atoms that are in equivalent molecular positions. The uncharacterised structure of the asolvate form C is found to contain a single formoterol ion and half a fumarate ion in its asymmetric unit. HETCOR experiments for the ethanolate and form C allow proton chemical shifts to be determined and give improved 13C resolution for the former compound. Desolvation of the solvates to form C has been monitored under the conditions of the NMR experiment. Differential rates of phenylene ring flipping are observed in the different forms. Carbon‐13 relaxation times and 2H NMR are used to probe dynamics of the fumarate ion. Copyright © 2012 John Wiley & Sons, Ltd.
Qualitative and Semi‐quantitative Analysis of Phenolics in Eucalyptus globulus Leaves by High‐performance Liquid Chromatography Coupled with Diode Array Detection and Electrospray Ionisation Mass Spectrometry
Authors: Boulekbache‐Makhlouf Lila , Meudec Emmanuelle , Mazauric Jean‐Paul , Madani Khodir , Cheynier Véronique
Published: August 2012

Introduction

Eucalyptus species are widely cultivated in Mediterranean regions. Moreover, plants of this family have been utilized for medicinal purposes. A number of studies have been devoted to the identification of eucalypt phenolics, all of them have focused on specific families of compounds, and no exhaustive profiling has been reported in leaves of this plant.

Objective

To develop methods that allows the identification and quantification of different classes of phenolics in Eucalyptus globulus leaf.

Methodology

Acetonic extract was fractionated by chromatography on a Sephadex LH‐20 column using consecutive elution with ethanol, methanol and aqueous acetone (60%). High‐performance liquid chromatography coupled with diode array detection and electrospray ionization mass spectrometry (HPLC‐DAD‐ESI/MS) were applied to determine the structure of different compounds. Quantities were evaluated from peak areas in the HPLC profile, using external calibration curves.

Results

Fractionation of acetonic extract yielded three fractions: F1, F2 and F3. In total 39 phenolic compounds are detected. Among them: 16 hydrolyzable tannins, 3 terpenyl derivatives, 12 ellagic acid derivatives, 5 flavonols, 2 hydroxybenzoic acids and 1 formylated phloroglucinol. 26 compounds described in this study have not previously detected in leaves of this plant and this is the first report of quercetin 3‐O‐β‐galactoside‐6”‐O‐gallate and cypellogin A and B, in E. globulus plant. Quantitatively, ellagic acid derivatives and sideroxylonal A or B are largely predominant.

Conclusion

Fractionation of crude extract by chromatography on Sephadex LH‐20 was efficient to separate different molecular weight compounds. HPLC‐DAD‐ESI/MS enabled detection of gallotannin, ellagitannin and flavonol derivatives, in leaves of E. globulus. Copyright © 2012 John Wiley & Sons, Ltd.
The effect of molecular weight and catalyst concentration on catalytic activity in mechanochemically activated transesterification using silver(I)‐N‐heterocyclic carbene latent catalysts
Authors: Groote Ramon , van Haandel Lennart , Sijbesma Rint P.
Published: August 2012

We have investigated the effect of the concentration and molecular weight on the activity of polymeric silver(I)‐NHC (NHC = N‐heterocyclic carbene) catalyst complexes in ultrasound‐induced mechanochemical catalyst activation. A strong dependence of the turnover number (TON) on initial catalyst concentration was observed in the transesterification of vinyl acetate with benzyl alcohol. The main findings of this study are that the concentration and molecular weight effects on TON are caused by competition between mechanochemical catalyst activation and deactivation, most likely by reactive species produced during the sonication process. Performing the transesterification reaction under radical‐suppressing conditions resulted in a significant increase of TON. This result clearly demonstrates the increased catalyst lifetime when reducing the amount of sonochemical impurities, and it highlights the importance of controlling and suppressing secondary, sonochemical processes when using ultrasound‐induced mechanochemical generation of reactive species such as catalysts. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012
Synthesis of well‐defined chitosan‐based tricomponent copolymers for constructing multifunctional delivery systems
Authors: Yu Lin , Cao Moyuan , Zhang Haiwen , Xiong Han , Jin Yucun , Lu Yi , Jia Haiyan , Luo Dongsheng , Wang Liqun , Jiang Hongliang
Published: August 2012

Chitosan‐based tricomponent copolymers, chitosan‐g‐poly(ε‐caprolactone)‐(g‐poly(oligo(ethylene glycol) methacrylate)) (CS‐PCL‐POEGMA, CPP), are synthesized as multifunctional nanocarriers for antitumor therapy. 2‐Bromoisobutyric acid and PCL are first site‐specifically conjugated onto the hydroxy groups of chitosan backbone through conventional coupling chemistry to give CS‐PCL‐Br using sodium dodecyl sulfate–chitosan complex as an organosoluble intermediate. CPP‐PCL‐Br is further used for initiating the single electron transfer‐living radical polymerization of OEGMA in the mixed solvent of dimethyl sulfoxide and lactic acid, yielding CPP. One‐pot reaction of CPP with a small amount of NaN3 under the catalysis of Cu(I)Br/tris‐(2‐dimethylaminoethyl)amine converts the bromo ends of POEGMA grafts to azide functionality, which is used for conjugation of folic acid targeting moiety via azide–alkyne click reactions. The resultant tricomponent copolymers can assemble into spherical micelles with the capacity of coincorporating indocyanine green and Doxorubicin through electrostatic and hydrophobic interactions, respectively. The dual‐agent‐loaded micelles display a combined effect for combating HepG2 cells when irradiated with near‐infrared laser. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012