bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA-programmed genome editing in human cells
Authors: Jinek Martin , East Alexandra , Cheng Aaron , Lin Steven , Ma Enbo , Doudna Jennifer
Published: January 2013

Type II CRISPR immune systems in bacteria use a dual RNA-guided DNA endonuclease, Cas9, to cleave foreign DNA at specific sites. We show here that Cas9 assembles with hybrid guide RNAs in human cells and can induce the formation of double-strand DNA breaks (DSBs) at a site complementary to the guide RNA sequence in genomic DNA. This cleavage activity requires both Cas9 and the complementary binding of the guide RNA. Experiments using extracts from transfected cells show that RNA expression and/or assembly into Cas9 is the limiting factor for Cas9-mediated DNA cleavage. In addition, we find that extension of the RNA sequence at the 3′ end enhances DNA targeting activity in vivo. These results show that RNA-programmed genome editing is a facile strategy for introducing site-specific genetic changes in human cells.
Effects of sulfide concentration, pH, and anoxia on photosynthesis and respiration of Zostera marina
Authors: Korhonen LK , Macías-Carranza V , Abdala R , Figueroa FL , Cabello-Pasini A
Published: January 2013

Sulfide produced in marine sediments by sulfate reduction is toxic for several macrophytes, and high sediment sulfide concentrations have been associated with seagrass die-off events. Sulfide has been shown to reduce growth in a number of seagrasses, but little is known about its effect on the photosynthetic and respiratory metabolism. Consequently, the aim of this research was to evaluate the effect of sulfide on photosynthesis and respiration of the seagrass Zostera marina. Photosynthetic oxygen evolution and respiration were determined polarographically, while the optimum quantum yield was used as a measure of the photosynthetic performance of photosystem II in the leaves of Z. marina. The results showed that sulfide concentrations of approximately 1000 uM could be considered an upper threshold limit for the survival of Z. marina in the coastal lagoons of Baja California (Mexico) studied. Respiration was not inhibited by sulfide concentrations up to

1000 ?M during 48-h incubations, while photosynthetic performance was reduced by short exposure to sulfide concentrations of 25 uM but also by long exposure to concentrations as low as 50 uM. This is the first study that shows that the photosynthetic capacity of Z. marina is not recovered once the sulfide-free conditions have been re-established.
Differences in diversity, structure, and variability between intertidal and subtidal meiofaunal assemblages
Authors: Riera R , Núñez J , Brito M C , Tuya F
Published: January 2013

Meiofaunal assemblages from intertidal and shallow subtidal seabeds were studied at two sites (one dominated by volcanic sands and the other by organogenic sands) at Tenerife (Canary Islands, NE Atlantic Ocean) throughout an entire year (May 2000–April 2001). Specifically, we aimed (i) to test for differences in diversity, structure, and stability between intertidal and subtidal meiofaunal assemblages, and (ii) to determine if differences in the meiofaunal assemblage structure may be explained by environmental factors (granulometric composition, availability of organic matter, and carbonate content in sediments). A total of 103,763 meiofaunal individuals were collected, including 203 species from 19 taxonomic groups (Acari, Amphipoda, Cnidaria, Copepoda, Echinodermata, Gastrotricha, Isopoda, Insecta, Kinorrhyncha, Misidacea, Nematoda, Nemertini, Oligochaeta, Ostracoda, Polychaeta, Priapulida, Sipuncula, Tanaidacea, and Turbellaria). Nematodes were the most abundant taxonomic group. Species diversity was higher in the subtidal than in the intertidal zone at both sites, as a result of the larger dominance of a few species in the intertidal zone. The meiofaunal assemblage structure was different between tidal levels at both sites, the intertidal presenting greater temporal variability (multivariate dispersion) in the meiofaunal assemblage structure than the subtidal. Sediment grain size, here quantified by the different granulometric fractions, explained the variability in meiofaunal assemblage structure to a greater extent than the percentage of carbonates, a variable linked to sediment origin. This study revealed differences in diversity, assemblage structure, and variability between intertidal and subtidal meiofauna.
Analysis of feeding behavior and food consumption rate of Atlantorchestoidea brasiliensis (Crustacea: Talitridae)
Authors: Veloso V Gomes , Sallorenzo I Azevedo , Andrade Barros WK , De Souza G Neves
Published: January 2013

Talitrid amphipods are considered one of the most important wrack-deposit consumers in the intertidal zone of sandy beaches due to their ability to remove extensive amounts of macrophytes. The quantity and composition of drift macrophytes can influence the consumption and demographic rates of talitrid species. However, on coasts with a low contribution of macrophytes, where organic material is typically composed of debris, algal fragments, and vascular plants, the feeding behavior of talitrids is poorly understood. Along the south coast of Brazil, the amphipod Atlantorchestoidea brasiliensis is the most abundant species of macrofauna on exposed sandy beaches that do not have a high abundance of macroalgal wrack. In order to understand the feeding behavior of this species, experiments on food preference and consumption rates were carried out, and the ability to feed on the surface or buried within the substrate was also tested. Food items offered included the sand crab Emerita brasiliensis, the wedge clam Donax hanleyanus, the mullet fish Mugil sp., and the alga Ulva sp., species that commonly comprise debris on the drift line. Adult amphipods showed a broad feeding range. The most commonly consumed food items were E. brasiliensis and D. hanleyanus, which were consumed more during the night, while Mugil sp. was the least consumed item during both the day and night. In the food preference trials, algal consumption was negligible, suggesting that feeding on debris is more important for this species. Amphipods preferred fresh algae rather than dried algae when simultaneously offered both food items. Our results indicate that talitrids have different feeding strategies and behavior according to the type of organic material deposited on the beach.
Microstructural Parameters and Their Effect on the Indentation Hardness of Electrodeposited and Annealed Nickel–Iron Micro‐Specimens
Authors: Schmitt Martin‐T. , Hoffmann Joachim E. , Eifler Dietmar
Published: January 2013

Using the direct‐LIGA technology, nickel–iron micro‐specimens are serially produced by a micro‐gear drive manufacturer and subsequently annealed within the temperature range between 180 and 800 °C. The microstructure (grain size, lattice strain, and texture) is characterized using XRD measurements. Following electrodeposition, nano‐crystalline microstructures result with grain size of approximately 10 nm. The transmission electron microscope images confirm the XRD results. The lattice strain decreases in the temperature range from 200 to 300 °C and grain growth results for an annealing temperature from approximately 260 °C. The annealing treatment produced no essential changes in the material's texture. Analysis of the indentation hardness and indentation modulus demonstrates considerable changes above 200 °C.
Catalytic Stereoselective Conjugate Addition of Oxindole to Electron‐Deficient Alkynes
Authors: Kang Guowei , Wu Quanquan , Liu Miaochang , Xu Qingfang , Chen Zunyang , Chen Weilong , Luo Yuqiang , Ye Wei , Jiang Jun , Wu Huayue
Published: January 2013

A Z/E‐selective and enantioselective conjugate addition of oxindoles to butyl but‐2‐ynedioate derivatives has been developed, providing a facile access to enantioenriched multifunctional olefins, which can be further converted into 3,3a‐ dihydro‐2H‐pyrrolo[3,4‐c]quinoline‐1,4(5H,9bH)‐dione derivatives via conventional operations.
Nitric oxide signaling in the brain: A new target for inhaled nitric oxide?
Authors: Charriaut‐Marlangue Christiane , Bonnin Philippe , Pham Hoa , Loron Gauthier , Leger Pierre‐Louis , Gressens Pierre , Renolleau Sylvain , Baud Olivier
Published: January 2013

Nitric oxide (NO) is a powerful vasodilator, involved in both physiological functions and pathophysiological alterations of various regulatory processes, for example, the maintenance of vascular tone and inflammation. The recently demonstrated impact of exogenous NO on the central nervous system extends its role under normal and pathological conditions. At times neuroprotective, at times neurotoxic, NO is capable of different effects depending upon the extent of cerebral damage, the cellular redox state, and the spatiotemporal coordinates and concentration at which it is synthesized. This review provides new insights into the short‐ and long‐term effects of endogenous and exogenous NO in brain injury. ANN NEUROL 2013;73:442–448
Elevated temperature and 6‐ to 7‐year outcome of neonatal encephalopathy
Authors: Laptook Abbot R. , McDonald Scott A. , Shankaran Seetha , Stephens Bonnie E. , Vohr Betty R. , Guillet Ronnie , Higgins Rosemary D. , Das Abhik ,   Extended Hypothermia Follow‐up Subcommittee of the National Institute of Child Health and Human Development Neonatal Research Network
Published: January 2013

Objective

A study was undertaken to determine whether higher temperature after hypoxia–ischemia is associated with death or intelligence quotient (IQ)<70 at 6 to 7 years among infants treated with intensive care without hypothermia.

Methods

Control infants (noncooled, n=106) of the National Institute of Child Health and Human Development Neonatal Research Network hypothermia trial had serial esophageal and skin temperatures over 72 hours. Each infant's temperature was ranked to derive an average of the upper and lower quartile, and median of each site. Temperatures were used in logistic regressions to determine adjusted associations with death or IQ<70 at 6 to 7 years. Secondary outcomes were death, IQ<70, and moderate/severe cerebral palsy (CP). IQ and motor function were assessed with Wechsler Scales for Children and Gross Motor Function Classification System. Results are odds ratio (OR; per degree Celsius increment within the quartile or median) and 95% confidence interval (CI).

Results

Primary outcome was available for 89 infants. At 6 to 7 years, death or IQ<70 occurred in 54 infants (37 deaths, 17 survivors with IQ<70) and moderate/severe CP in 15 infants. Death or IQ<70 was associated with the upper quartile average of esophageal (OR=7.3, 95% CI=2.0–26.3) and skin temperature (OR=3.5, 95% CI=1.2–10.4). CP was associated with the upper quartile average of esophageal (OR=12.5, 95% CI=1.02–155) and skin temperature (OR=10.3, 95% CI=1.3–80.2).

Interpretation

Among noncooled infants of a randomized trial, elevated temperatures during the first postnatal days are associated with increased odds of a worse outcome at 6 to 7 years. Ann Neurol 2013;73:520–528
Novel Cationic Quinazolin‐4(3H)‐one Conjugated Fullerene Nanoparticles as Antimycobacterial and Antimicrobial Agents
Authors: Patel Manishkumar B. , Harikrishnan Uma , Valand Nikunj N. , Modi Nishith R. , Menon Shobhana K.
Published: January 2013

A series of novel cationic fullerene derivatives bearing a substituted‐quinazolin‐4(3H)‐one moiety as a side arm were synthesized using the 1,3‐dipolar cycloaddition reaction of C60 with azomethine ylides generated from the corresponding Schiff bases of substituted quinazolinones. The synthesized compounds 5a–f were characterized by elemental analysis, FT‐IR, 1H NMR, 13C NMR, and ESI‐MS and screened for their antibacterial activity against Mycobacterium tuberculosis (H37RV) and antimicrobial activity against selected Gram‐positive (Staphylococcus aureus and S. pyogenes) and Gram‐negative (Pseudomonas aeruginosa, Klebsiella pneumonia and Escherichia coli) bacterial and fungal strains (Candida albicans, Aspergillus clavatus, and A. niger), respectively. All the compounds exhibited significant activity, with the most effective compounds having MIC values and zones of inhibition comparable to those of standard drugs.
Synthesis, Physical Properties, and Self‐Assembly of A Novel Asymmetric Aroyleneimidazophenazine
Authors: Zhao Jianfeng , Wong Jen It , Wang Chengyuan , Gao Junkuo , Ng Verena Zi Yun , Yang Hui Ying , Loo Say Chye Joachim , Zhang Qichun
Published: January 2013

The synthesis, physical properties, and self‐assembly of a novel asymmetric aroyleneimidazophenazine (IZ1) is reported. The as‐prepared IZ1 nanowires display an obvious red fluorescence. A heterojunction light‐emitting diode (LED) device with the structure ITO/IZ1 nanowires/p‐SiC/Al (10 nm)/Ti (80 nm)/Al (380 nm)/ITO was fabricated, and electroluminescence emission with two peaks at about 412 nm and 613 nm was detected with a forward bias ranging from 5 to 10 V.
Macrocephaly as a Clinical Indicator of Genetic Subtypes in Autism
Authors: Klein Steven , Sharifi‐Hannauer Pantea , Martinez‐Agosto Julian A.
Published: January 2013

An association between autism and macrocephaly has been previously described. A subset of cases with extreme macrocephaly (>3 standard deviation [SD], 99.7th percentile) have been correlated to mutations in the gene phosphatase and tensin homolog (PTEN). However, the phenotypic and genetic characterization of the remaining cases remains unclear. We report the phenotypic classification and genetic testing evaluation of a cohort of 33 patients with autism and macrocephaly. Within our cohort, we confirm the association of PTEN mutations and extreme macrocephaly (>3 SD, 99.7th percentile) and identify mutations in 22% of cases, including three novel PTEN mutations. In addition, we define three phenotypic subgroups: (a) those cases associated with somatic overgrowth, (b) those with disproportionate macrocephaly, and (c) those with relative macrocephaly. We have devised a novel way to segregate patients into these subgroups that will aide in the stratification of autism macrocephaly cases. Within these subgroups, we further expand the genetic etiologies for autism cases with macrocephaly by describing two novel suspected pathogenic copy number variants located at 6q23.2 and 10q24.32. These findings demonstrate the phenotypic heterogeneity of autism cases associated with macrocephaly and their genetic etiologies. The clinical yield from PTEN mutation analysis is 22% and 9% from chromosomal microarray (CMA) testing within this cohort. The identification of three distinct phenotypic subgroups within macrocephaly autism patients may allow for the identification of their respective distinct genetic etiologies that to date have remained elusive. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Pulsed electromagnetic fields on postmenopausal osteoporosis in southwest China: A randomized, active‐controlled clinical trial
Authors: Liu Hui‐Fang , Yang Lin , He Hong‐Chen , Zhou Jun , Liu Ying , Wang Chun‐Yan , Wu Yuan‐Chao , He Cheng‐Qi
Published: January 2013

A randomized, active‐controlled clinical trial was conducted to examine the effect of pulsed electromagnetic fields (PEMFs) on women with postmenopausal osteoporosis (PMO) in southwest China. Forty‐four participants were randomly assigned to receive alendronate or one course of PEMFs treatment. The primary endpoint was the mean percentage change in bone mineral density of the lumbar spine (BMDL), and secondary endpoints were the mean percentage changes in left proximal femur bone mineral density (BMDF), serum 25OH vitamin D3 (25(OH)D) concentrations, total lower‐extremity manual muscle test (LE MMT) score, and Berg Balance Scale (BBS) score. The BMDL, BMDF, total LE MMT score and BBS score were recorded at baseline, 5, 12, and 24 weeks. Serum concentrations of 25(OH)D were measured at baseline and 5 weeks. Using a mixed linear model, there was no significant treatment difference between the two groups in the BMDL, BMDF, total LE MMT score, and BBS score (P ≥ 0.05). For 25(OH)D concentrations, the effects were also comparable between the two groups (P ≥ 0.05) with the Mann–Whitney's U‐test. These results suggested that a course of PEMFs treatment with specific parameters was as effective as alendronate in treating PMO within 24 weeks. Bioelectromagnetics 34:323–332, 2013. © 2012 Wiley Periodicals, Inc.
Isolation and characterization of antibody fragments selective for specific protein morphologies from nanogram antigen samples
Authors: Kasturirangan Srinath , Reasoner Tim , Schulz Philip , Boddapati Shanta , Emadi Sharareh , Valla Jon , Sierks Michael R.
Published: January 2013

We developed atomic force microscope (AFM)‐based protocols that enable isolation and characterization of antibody‐based reagents that selectively bind target protein variants using low nanogram amounts or less of unpurified starting material. We isolated single‐chain antibody fragments (scFvs) that specifically recognize an oligomeric beta‐amyloid (Aβ) species correlated with Alzheimer's disease (AD) using only a few nanograms of an enriched but not purified sample obtained from human AD brain tissue. We used several subtractive panning steps to remove all phage binding nondesired antigens and then used a single positive panning step using minimal antigen. We also used AFM to characterize the specificity of the isolated clones, again using minimal material, selecting the C6 scFv based on expression levels. We show that C6 selectively binds cell and brain‐derived oligomeric Aβ. The protocols described are readily adapted to isolating antibody‐based reagents against other antigenic targets with limited availability. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29: 463–471, 2013
Continuous rhamnolipid production using denitrifying Pseudomonas aeruginosa cells in hollow‐fiber bioreactor
Authors: Pinzon Neissa M. , Cook Aaron G. , Ju Lu‐Kwang
Published: January 2013

Rhamnolipids are high‐value effective biosurfactants produced by Pseudomonas aeruginosa. Large‐scale production of rhamnolipids is still challenging especially under free‐cell aerobic conditions in which the highly foaming nature of the culture broth reduces the productivity of the process. Immobilized systems relying on oxygen as electron acceptor have been previously investigated but oxygen transfer limitation presents difficulties for continuous rhamnolipid production. A coupled system using immobilized cells and nitrate instead of oxygen as electron acceptor taking advantage of the ability of P. aeruginosa to perform nitrate respiration was evaluated. This denitrification‐based immobilized approach based on a hollow‐fiber setup eliminated the transfer limitation problems and was found suitable for continuous rhamnolipid production in a period longer than 1,500 h. It completely eliminated the foaming difficulties related to aerobic systems with a comparable specific productivity of 0.017 g/(g dry cells)‐h and allowed easy recovery of rhamnolipids from the cell‐free medium. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29: 346–351, 2013
Functionalization of the 3′‐Ends of DNA and RNA Strands with N‐ethyl‐N‐coupled Nucleosides: A Promising Approach To Avoid 3′‐Exonuclease‐Catalyzed Hydrolysis of Therapeutic Oligonucleotides
Authors: Terrazas Montserrat , Alagia Adele , Faustino Ignacio , Orozco Modesto , Eritja Ramon
Published: January 2013

The development of nucleic acid derivatives to generate novel medical treatments has become increasingly popular, but the high vulnerability of oligonucleotides to nucleases limits their practical use. We explored the possibility of increasing the stability against 3′‐exonucleases by replacing the two 3′‐terminal nucleotides by N‐ethyl‐N‐coupled nucleosides. Molecular dynamics simulations of 3′‐N‐ethyl‐N‐modified DNA:Klenow fragment complexes suggested that this kind of alteration has negative effects on the correct positioning of the adjacent scissile phosphodiester bond at the active site of the enzyme, and accordingly was expected to protect the oligonucleotide from degradation. We verified that these modifications conferred complete resistance to 3′‐exonucleases. Furthermore, cellular RNAi experiments with 3′‐N‐ethyl‐N‐modified siRNAs showed that these modifications were compatible with the RNAi machinery. Overall, our experimental and theoretical studies strongly suggest that these modified oligonucleotides could be valuable for therapeutic applications.
PTCA with drug‐coated balloons is associated with immediate decrease of coronary flow reserve
Authors: Young Mabelle , Cuculi Florim , Erne Paul
Published: January 2013

Introduction

Drug‐coated balloons (DCB) are being increasingly used in interventional cardiology. The effect of DCB on acute changes of coronary flow reserve (CFR) has never been reported.

Methods

Patients with in‐stent restenosis or with contraindication for use of clopidogrel were included in this study. The FloWire was used to assess CFR before and immediately after conventional balloon angioplasty and after the use of In.Pact, a paclitaxel‐coated balloon. In a sub‐selection of patients, CFR was measured immediately and then 2, 5, and 10 min post‐DCB.

Results

Thirty patients (18 males, 60%) with a total of 32 lesions were studied. Comparison of CFR pre‐ and post‐conventional balloon angioplasty was not statistically significant (P = 0.95). CFR dropped significantly after the use of In.Pact (n = 32, 1.59 ± 0.49 vs. 1.22 ± 0.28, P < 0.0001) and showed a statistically significant improvement over 10 min in a subset of patients (n = 6, P = 0.01). Implantation of a coronary stent after the use of In.Pact rapidly improved CFR (n = 10, P = 0.0004).

Conclusions

We describe a novel phenomenon of acute decrease in CFR after the use of DCB. This phenomenon is temporary and spontaneously improves after approximately 10 min. The exact pathophysiological mechanism remains unclear and further studies are warranted to study the long‐term effects of acute CFR drop after use of DCB. © 2011 Wiley Periodicals, Inc.
A case of CTO treated with minimum use of contrast media
Authors: Uehara Yoshiki , Shimizu Mitsuyuki , Yoshimura Michihiro
Published: January 2013

The retrograde approach is a novel technique for improving the success rate of guidewire passage through chronic total occlusion (CTO). In addition, this technique, especially when intravascular ultrasound‐guided reverse controlled antegrade and retrograde subintimal tracking is employed, may help the operator to save on the contrast media used. In the case reported here, only 10 ml of contrast media was used in percutaneous coronary intervention for CTO. © 2013 Wiley Periodicals, Inc.
Stent angioplasty to relieve left pulmonary artery obstruction caused by patent ductus arteriosus device occlusion
Authors: Dean Peter N. , Slack Michael C.
Published: January 2013

A 7‐month‐old patient in congestive heart failure due to a moderate sized patent ductus arteriosus (PDA) underwent uncomplicated implantation of an Amplatzer Ductal Occluder (ADO1). Two months after percutaneous device PDA closure, left pulmonary artery (LPA) stenosis was discovered. Rather than spontaneous improvement as reported in previous cases, our patient's LPA stenosis progressed in severity 7 months after ADO1 placement. A catheterization demonstrated a 32 mm Hg peak gradient from her main pulmonary artery to her LPA. She underwent successful stent angioplasty of her LPA with an excellent result and preserved PDA closure. This case demonstrates that stent angioplasty is a feasible an effective method of relieving LPA obstruction caused by a PDA occluder device. Additionally, despite slight deflection by the stent, the ADO1 device continued to provide complete ductal closure. Stent angioplasty should be considered in patients who have LPA stenosis caused by ADO1 occluder device that does not improve over time. © 2013 Wiley Periodicals, Inc.
Efficient Tertiary Amine/Weak Acid Bifunctional Mesoporous Silica Catalysts for Michael Addition Reactions
Authors: Das Sayantani , Goswami Anandarup , Murali Nagarajan , Asefa Tewodros
Published: January 2013

We describe the development and application of efficient bifunctional acid–base mesoporous silica catalysts, denoted hereafter as Ext‐SBA‐15‐NMe2, comprising tertiary amine and silanol (weak acid) groups for the Michael addition reaction. The catalysts were synthesized by grafting tertiary amine containing organosilane into the mesoporous channel pores of SBA‐15 mesoporous silica in polar protic solvent (isopropyl alcohol) or nonpolar solvent (toluene). The resulting materials, Ext‐SBA‐15‐NMe2‐IPA or Ext‐SBA‐15‐NMe2‐Tol, respectively, were used as catalysts for the Michael addition reactions between trans‐β‐nitrostyrene(s) and active methylene compounds, such as malononitrile, acetylacetone, and diethylmalonate, at different temperatures. A variable‐temperature NMR‐array technique was used to monitor the reactant conversion and the reaction progress. Among the active methylene compounds tested with trans‐β‐nitrostyrene, malononitrile gave the highest conversion of 90 % in 0.3 h at 0 °C if catalyzed by the catalyst Ext‐SBA‐15‐NMe2‐IPA, the silanol groups of which were not passivated by trimethysilyl (SiMe3) groups. Compared with Ext‐SBA‐15‐NMe2‐Tol, the Ext‐SBA‐15‐NMe2‐IPA material (whose the amine groups were grafted in polar‐protic solvents), in particular, demonstrated an effective cooperative bifunctional catalysis because of its optimized proportions of tertiary amine groups and a significant number of surface silanol groups that were judiciously left behind on the material with this optimized synthetic strategy. The catalytic activity of this material was found to be significantly higher than that of the corresponding material that was grafted in toluene and that contained less optimized proportions of these two catalytic groups (i.e., amine and silanol groups). The bifunctional catalysts also showed good recyclability upon washing with acetone, which offered an effective way of regenerating the catalyst free from any undesired product/substrate bound on the surface of the catalysts.
Unsymmetrical Binding Modes of the HOPNO Inhibitor of Tyrosinase: From Model Complexes to the Enzyme
Authors: Bochot Constance , Favre Elisabeth , Dubois Carole , Baptiste Benoit , Bubacco Luigi , Carrupt Pierre‐Alain , Gellon Gisèle , Hardré Renaud , Luneau Dominique , Moreau Yohann , Nurisso Alessandra , Réglier Marius , Serratrice Guy , Belle Catherine , Jamet Hélène
Published: January 2013

The deciphering of the binding mode of tyrosinase (Ty) inhibitors is essential to understand how to regulate the tyrosinase activity. In this paper, by combining experimental and theoretical methods, we studied an unsymmetrical tyrosinase functional model and its interaction with 2‐hydroxypyridine‐N‐oxide (HOPNO), a new and efficient competitive inhibitor for bacterial Ty. The tyrosinase model was a dinuclear copper complex bridged by a chelated ring with two different complexing arms (namely (bis(2‐ethylpyridyl)amino)methyl and (bis(2‐methylpyridyl)amino)methyl). The geometrical asymmetry of the complex induces an unsymmetrical binding of HOPNO. Comparisons have been made with the binding modes obtained on similar symmetrical complexes. Finally, by using quantum mechanics/molecular mechanics (QM/MM) calculations, we studied the binding mode in tyrosinase from a bacterial source. A new unsymmetrical binding mode was obtained, which was linked to the second coordination sphere of the enzyme.
Solvatochromic Behavior of Chiral Mesoporous Metal–Organic Frameworks and Their Applications for Sensing Small Molecules and Separating Cationic Dyes
Authors: Sun Chun‐Yi , Wang Xin‐Long , Qin Chao , Jin Jun‐Ling , Su Zhong‐Min , Huang Peng , Shao Kui‐Zhan
Published: January 2013

Two anionic metal–organic frameworks (MOFs) with 1D mesoporous tubes (1) and chiral mesoporous cages (2) have been rationally constructed by means of a predesigned size‐extended hexatopic ligand, namely, 5,5′,5′′‐(1,3,5‐triazine‐2,4,6‐triyl)tris‐ (azanediyl)triisophthalate (TATAT). Charge neutrality is achieved by protonated dimethylamine cations. Notably, the two MOFs can be used to separate large molecules based on ionic selectivity rather than the size‐exclusion effect so far reported in the literature. Owing to the imino triazine backbone and carboxyl groups of the hexatopic ligand, which provide important host–guest interactions, rare solvatochromic phenomena of 1 and 2 are observed on incorporating acetone and ethanol guests. Furthermore, guest‐dependent luminescence properties of compound 2 were investigated, and the results show that luminescence intensity is significantly enhanced in toluene and benzene, while quenching effects are observed in acetone and ethanol. Thus, compound 2 may be a potential material for luminescent probes.
Stepwise Metal–Ligand Cooperation by a Reversible Aromatization/Deconjugation Sequence in Ruthenium Complexes with a Tetradentate Phenanthroline‐Based Ligand
Authors: Langer Robert , Fuchs Ido , Vogt Matthias , Balaraman Ekambaram , Diskin‐Posner Yael , Shimon Linda J. W. , Ben‐David Yehoshoa , Milstein David
Published: January 2013

The synthesis and reactivity of ruthenium complexes containing the tetradentate phenanthroline‐based phosphine ligand 2,9‐bis((di‐tert‐butylphosphino)methyl)‐1,10‐phenanthroline (PPhenP) is described. The hydrido chloro complex [RuHCl(PPhenP)] (2) undergoes facile dearomatization upon deprotonation of the benzylic position, to give [RuH(PPhenP‐H)] (4). Addition of dihydrogen to 4 causes rearomatization of the phenanthroline moiety to trans‐[Ru(H)2(PPhenP)] (5), followed by hydrogenation of an aromatic heterocycle in the ligand backbone, to give a new dearomatized and deconjugated complex [RuH(PPhenP*‐H)] (6). These aromatization/deconjugation steps of the coordinated ligand were demonstrated to be reversible and operative in the dehydrogenation of primary alcohols without the need for a hydrogen acceptor. This aromatization/deconjugation sequence constitutes an unprecedented mode of a stepwise cooperation between the metal center and the coordinated ligand.
Enhanced Performance of Benzothieno[3,2‐b]thiophene (BTT)‐Based Bottom‐Contact Thin‐Film Transistors
Authors: Huang Peng‐Yi , Chen Liang‐Hsiang , Chen Yu‐Yuan , Chang Wen‐Jung , Wang Juin‐Jie , Lii Kwang‐Hwa , Yan Jing‐Yi , Ho Jia‐Chong , Lee Cheng‐Chung , Kim Choongik , Chen Ming‐Chou
Published: January 2013

Three new benzothieno[3,2‐b]thiophene (BTT; 1) derivatives, which were end‐functionalized with phenyl (BTT‐P; 2), benzothiophenyl (BTT‐BT; 3), and benzothieno[3,2‐b]thiophenyl groups (BBTT; 4; dimer of 1), were synthesized and characterized in organic thin‐film transistors (OTFTs). A new and improved synthetic method for BTTs was developed, which enabled the efficient realization of new BTT‐based semiconductors. The crystal structure of BBTT was determined by single‐crystal X‐ray diffraction. Within this family, BBTT, which had the largest conjugation of the BTT derivatives in this study, exhibited the highest p‐channel characteristic, with a carrier mobility as high as 0.22 cm2 V−1 s−1 and a current on/off ratio of 1×107, as well as good ambient stability for bottom‐contact/bottom‐gate OTFT devices. The device characteristics were correlated with the film morphologies and microstructures of the corresponding compounds.
Variable selection and estimation for multivariate panel count data via the seamless‐${\it L}_{{\rm 0}}$ penalty
Authors: Zhang Haixiang , Sun Jianguo , Wang Dehui
Published: January 2013

This paper considers regression analysis of multivariate panel count data with the focus on variable selection and estimation of significant covariate effects. For the problem, we adopt the penalized estimating equation approach with a focus on the use of the seamless‐$L_0$ penalty. The proposed approach selects variables and estimates regression coefficients simultaneously and the asymptotic properties of the resulting estimates are established. The procedure can be easily carried out with the Newton–Raphson algorithm and is evaluated by simulation studies. Also it is applied to a motivating data set arising from a skin cancer study. The Canadian Journal of Statistics 41: 368–385; 2013 © 2013 Statistical Society of Canada
On collegiality and role models
Authors: Khuri Fadlo R.
Published: January 2013

In this editorial, Dr. Fadlo Khuri discusses the process of peer reviewing submissions to Cancer.
Comparison of age at natural menopause in BRCA1/2 mutation carriers with a non–clinic‐based sample of women in northern California
Authors: Lin Wayne T. , Beattie Mary , Chen Lee‐may , Oktay Kutluk , Crawford Sybil L. , Gold Ellen B. , Cedars Marcelle , Rosen Mitchell
Published: January 2013

BACKGROUND:

Germline mutations in BRCA1 and BRCA2 (BRCA1/2) are related to an increased lifetime risk of developing breast and ovarian cancer. Although risk‐reducing salpingo‐oophorectomy reduces the risk of both cancers, loss of fertility is a major concern. A recent study suggested an association between BRCA1 mutation and occult primary ovarian insufficiency. The objective of the current study was to determine whether BRCA1/2 mutation carriers have an earlier onset of natural menopause compared with unaffected women.

METHODS:

White carriers of the BRCA1/2 gene (n = 382) were identified within the Breast Cancer Risk Program Registry at the University of California at San Francisco and compared with non–clinic‐based white women in northern California (n = 765). The 2 groups were compared with regard to median age at the time of natural menopause before and after adjustment for known risk factors, and the role of smoking within each group was examined using the Kaplan‐Meier approach for unadjusted analyses and Cox proportional hazards regression analyses for adjusted analyses.

RESULTS:

The median age at the time of natural menopause in the BRCA1/2 carriers was significantly younger than among the unaffected sample (50 years vs 53 years; P < .001). The unadjusted hazard ratio for natural menopause when comparing BRCA1/2 carriers with unaffected women was 4.06 (95% confidence interval, 3.03‐5.45) and was 3.98 (95% confidence interval, 2.87‐5.53) after adjusting for smoking, parity, and oral contraceptive use. For BRCA1/2 carriers who were current heavy smokers (smoking ≥ 20 cigarettes/day), the median age at natural menopause was 46 years versus 49 years for nonsmokers (P = .027).

CONCLUSIONS:

The BRCA1/2 mutation was associated with a significantly earlier age at natural menopause, and heavy smoking compounded this risk. Because the relationship between menopause and the end of natural fertility is considered to be fixed, these findings suggest the risk of earlier infertility among BRCA1/2 carriers. Cancer 2013. © 2012 American Cancer Society.
Pericardial fluid cytology: An analysis of 128 specimens over a 6‐year period
Authors: Dragoescu Ema A. , Liu Lina
Published: January 2013

BACKGROUND

Pericardial fluid (PF) accumulates through various mechanisms and cytology is part of the workup to determine the specific etiology, primarily to rule in or rule out malignancy. To the best of the authors' knowledge, the current study is the largest systematic evaluation of PF cytology performed to date.

METHODS

PF specimens collected over 6 years were retrieved. Clinical history, laboratory, cytologic, and pericardial biopsy results were recorded.

RESULTS

A total of 128 PF specimens were obtained from 113 patients (56 males and 57 females), representing 4.5% of all fluids. Of these, 95 cases (74.2%) were benign, 2 (1.6%) had “severely atypical cells, ” and 31 cases (24.2%) were malignant. The most common etiologies for benign PF specimens were neoplasm (23.1%), idiopathic (19%), infection (14.7%), and connective tissue disease (12.6%). The most common neoplasm producing malignant PF was lung carcinoma, both in males (75%) and females (52.2%), with adenocarcinoma being the most common type (72.2%). In females, breast carcinoma was the second most common neoplasm (39.1%). Approximately 87.1% of patients with malignant PF specimens had a prior history of malignancy and approximately 32.7% underwent a concomitant pericardial biopsy. The false‐negative rate for cytology was 14.7% (hematologic malignancies [2 cases], metastatic sarcoma [1 case], and sarcoidosis [1 case] not detected) and that for pericardial biopsy was 40% (metastatic carcinoma [4 cases] not detected).

CONCLUSIONS

PF specimens are uncommon. A specific interpretation is rendered in approximately 98.4% of cases. Lung carcinoma is the most common tumor to produce malignant PF in both males and females. Approximately 87.1% of patients with malignant PF have a known history of malignancy. Although cytology is superior to pericardial biopsy in diagnosing metastatic carcinoma, other tumors may go undetected in the PF. Cancer (Cancer Cytopathol) 2013;121:242–51. © 2013 American Cancer Society.
EZH2 and CD79B mutational status over time in B‐cell non‐Hodgkin lymphomas detected by high‐throughput sequencing using minimal samples
Authors: Saieg Mauro Ajaj , Geddie William R. , Boerner Scott L. , Bailey Denis , Crump Michael , da Cunha Santos Gilda
Published: January 2013

BACKGROUND

Numerous genomic abnormalities in B‐cell non‐Hodgkin lymphomas (NHLs) have been revealed by novel high‐throughput technologies, including recurrent mutations in EZH2 (enhancer of zeste homolog 2) and CD79B (B cell antigen receptor complex‐associated protein beta chain) genes. This study sought to determine the evolution of the mutational status of EZH2 and CD79B over time in different samples from the same patient in a cohort of B‐cell NHLs, through use of a customized multiplex mutation assay.

METHODS

DNA that was extracted from cytological material stored on FTA cards as well as from additional specimens, including archived frozen and formalin‐fixed histological specimens, archived stained smears, and cytospin preparations, were submitted to a multiplex mutation assay specifically designed for the detection of point mutations involving EZH2 and CD79B, using MassARRAY spectrometry followed by Sanger sequencing.

RESULTS

All 121 samples from 80 B‐cell NHL cases were successfully analyzed. Mutations in EZH2 (Y646) and CD79B (Y196) were detected in 13.2% and 8% of the samples, respectively, almost exclusively in follicular lymphomas and diffuse large B‐cell lymphomas. In one‐third of the positive cases, a wild type was detected in a different sample from the same patient during follow‐up.

CONCLUSIONS

Testing multiple minimal tissue samples using a high‐throughput multiplex platform exponentially increases tissue availability for molecular analysis and might facilitate future studies of tumor progression and the related molecular events. Mutational status of EZH2 and CD79B may vary in B‐cell NHL samples over time and support the concept that individualized therapy should be based on molecular findings at the time of treatment, rather than on results obtained from previous specimens. Cancer (Cancer Cytopathol) 2013;121:377–386. © 2013 American Cancer Society.
ON cone bipolar cell axonal synapses in the OFF inner plexiform layer of the rabbit retina
Authors: Lauritzen J. Scott , Anderson James R. , Jones Bryan W. , Watt Carl B. , Mohammed Shoeb , Hoang John V. , Marc Robert E.
Published: January 2013

Analysis of the rabbit retinal connectome RC1 reveals that the division between the ON and the OFF inner plexiform layer (IPL) is not structurally absolute. ON cone bipolar cells make noncanonical axonal synapses onto specific targets and receive amacrine cell synapses in the nominal OFF layer, creating novel motifs, including inhibitory crossover networks. Automated transmission electron microscopic imaging, molecular tagging, tracing, and rendering of ∼400 bipolar cells reveals axonal ribbons in 36% of ON cone bipolar cells, throughout the OFF IPL. The targets include γ‐aminobutyrate (GABA)‐positive amacrine cells (γACs), glycine‐positive amacrine cells (GACs), and ganglion cells. Most ON cone bipolar cell axonal contacts target GACs driven by OFF cone bipolar cells, forming new architectures for generating ON–OFF amacrine cells. Many of these ON–OFF GACs target ON cone bipolar cell axons, ON γACs, and/or ON–OFF ganglion cells, representing widespread mechanisms for OFF to ON crossover inhibition. Other targets include OFF γACs presynaptic to OFF bipolar cells, forming γAC‐mediated crossover motifs. ON cone bipolar cell axonal ribbons drive bistratified ON–OFF ganglion cells in the OFF layer and provide ON drive to polarity‐appropriate targets such as bistratified diving ganglion cells (bsdGCs). The targeting precision of ON cone bipolar cell axonal synapses shows that this drive incidence is necessarily a joint distribution of cone bipolar cell axonal frequency and target cell trajectories through a given volume of the OFF layer. Such joint distribution sampling is likely common when targets are sparser than sources and when sources are coupled, as are ON cone bipolar cells. J. Comp. Neurol. 521:977–1000, 2013. © 2012 Wiley Periodicals, Inc.
Sexual dimorphism in the olfactory system of a solitary and a eusocial bee species
Authors: Streinzer Martin , Kelber Christina , Pfabigan Sarah , Kleineidam Christoph J. , Spaethe Johannes
Published: January 2013

Sexually dimorphic sensory systems are common in Hymenoptera and are considered to result from sex‐specific selection pressures. An extreme example of sensory dimorphism is found in the solitary bee tribe Eucerini. Males of long‐horned bees bear antennae that exceed body length. This study investigated the pronounced sexual dimorphism of the peripheral olfactory system and its representation in higher brain centers of the species Eucera berlandi. Eucera males have elongated antennae, with 10 times more pore plates and three times more olfactory receptor neurons than females. The male antennal lobe (AL) comprises fewer glomeruli than the female AL (∼100 vs. ∼130), of which four are male‐specific macroglomeruli. No sex differences were found in the relative volume of the mushroom bodies, a higher order neuropil essential for learning and memory in Hymenoptera. Compared with the Western honeybee, the degree of sexual dimorphism in Eucera is more pronounced at the periphery. In contrast, sex differences in glomerular numbers are higher in the eusocial honeybee and a sexual dimorphism of the relative investment in mushroom body tissue is observed only in Apis. The observed differences between the eusocial and the solitary bee species may reflect differences in male‐specific behavioral traits and associated selection pressures, which are discussed in brief. J. Comp. Neurol. 521:2742–2755, 2013. © 2013 Wiley Periodicals, Inc.
BSNet: a network‐based framework for service‐oriented business ecosystem management
Authors: Huang Keman , Fan Yushun , Tan Wei , Qian Minghui
Published: January 2013

As enterprises turning to SOA, services‐oriented business ecosystem (SOBE) has become an important pattern for the organization and management of the massive business services. At the same time, the emergence of Internet of Services (IOS) provides a business model in which service vendors and consumers can interact with each other via the Internet. This paradigm makes it possible that the services in SOBE are managed in an autonomous and coordinated manner. The challenge here is to organize these massive business services, coordinate, and federate them to achieve the benefits of SOA. To address these challenges, this paper presents BSNet, a framework on the basis of the service correlation networks to manage the SOBE. The model consists of a who‐what‐how service correlation network that captures the various relations in SOBE. Finally, a prototype system is developed, and a simulated case study is provided to show the expanded value of our network‐based framework. Copyright © 2013 John Wiley & Sons, Ltd.
ipcmd: a command‐line interface to System V semaphores and message queues
Authors: Weeks Nathan T. , Kraeva Marina , Luecke Glenn R.
Published: January 2013

Concurrent programming has become a common means to harness the potential performance of multi‐core processors. System V (SysV) message queues and semaphores have been used since the mid 1970s to implement inter‐process concurrency, but they are difficult to use, and bindings exist for few programming languages. This paper introduces ipcmd, a high‐level command‐line interface to SysV message queues and semaphores. ipcmd provides an easy‐to‐use interface for synchronizing concurrent processes to allow application developers to efficiently prototype, debug, and test the use of SysV semaphores and message queues in applications. Easy‐to‐understand applications of semaphores are illustrated using simple shell scripts. Copyright © 2013 John Wiley & Sons, Ltd.
Synthesis of β‐Substituted Porphyrin Derivatives Containing Heterocyclic Moieties as Potential Photosensitizers Against Cutaneous Leishmaniasis
Authors: Bastos Mônica M. , Gomes Ana T. P. C. , Neves Maria G. P. M. S. , Silva Artur M. S. , Santos‐Filho Osvaldo A. , Boechat Núbia , Cavaleiro José A. S.
Published: January 2013

This work reports the synthesis of porphyrin derivatives with potential leishmanicidal activity. The β‐substituents contain amine/imine‐heterocyclic features. Molecular docking simulations of these compounds to a model of the enzyme arginase from Leishmania amazonensis were carried out. Singlet oxygen generation studies have been also considered. The obtained leishmanicidal properties show that these compounds can be considered as prototypes for future cutaneous antileishmaniasis agents.
Studies on the Regioselectivity of the Cyclization of Tryptophanol‐Derived Oxazolopiperidone Lactams
Authors: Amat Mercedes , Llor Núria , Subrizi Fabiana , Pérez Maria , Molins Elies , Bosch Joan
Published: January 2013

Cyclization of the lactam carbonyl on the indole ring in tryptophanol‐derived oxazolopiperidone lactams 2 and 6, under the classical POCl3‐promoted Bischler–Napieralski conditions and under neutral conditions via the corresponding thiolactam, has been studied. Whereas tricyclic lactam 2 only leads to products coming from an α‐amidoalkylation process, bicyclic lactam 6 undergoes cyclization on the lactam carbonyl, leading to the expected indolo[2,3‐a]quinolizidine derivatives.
Low nM Detection Limits at Porous 1–3 nm Thick Membrane‐Coated Nanostructured Microdisk Electrodes
Authors: Boateng Abraham , Irague Florian , Brajter‐Toth Anna
Published: January 2013

Low (15 nM) limits of detection (LOD) of dopamine were obtained at porous 1–3 nm‐thick overoxidized polypyrrole (OPPY) membrane‐coated microdisk carbon fiber electrodes of small size (r=3.5 µm). The excellent mass transport through the porous OPPY membrane (efficiency as good as solution transport) contributes to the low LOD, together with dopamine preconcentration in the membrane. Structural characterization of the membrane coated electrodes confirms the contribution of membrane nanostructure to the high sensitivity and the low LOD.