bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Oligomeric Zinc Complexes with Bicyclic and Acyclic Guanidinate Ligands
Authors: Neuhäuser Christiane , Reinmuth Matthias , Kaifer Elisabeth , Himmel Hans‐Jörg
Published: February 2012

Zinc dichloride and dimethylzinc were treated with several acyclic and bicyclic guanidines. Three different bicyclic guanidines and their potassium guanidinate salts were treated with ZnCl2. The reaction with the neutral guanidines afforded mononuclear complexes, stabilized by intramolecular hydrogen bonding. The reaction with the potassium guanidinate salts led to trinuclear complexes, which were extremely water sensitive. The reaction in the presence of added water furnished a tetranuclear complex with a central OZn4 unit in good yield, to which six guanidinate ligands were bound. The reaction of dimethylzinc with 2‐[N,N′‐diisopropylguanidino]pyridine and 2‐[N,N′‐diisopropylguanidino]quinoline afforded di‐ and tetranuclear Zn methyl complexes with mono‐ and dianionic guanidinate ligands. Dinuclear complexes of the monoanionic guanidinate ligands were formed at room temperature. At higher temperatures (75 °C), complete deprotonation of the guanidino groups and formation of tetranuclear Zn alkyl complexes was observed, which feature low‐coordinate zinc sites.
Coordinating Properties of Pyrone and Pyridinone Derivatives, Tropolone and Catechol toward the VO2+ Ion: An Experimental and Computational Approach
Authors: Sanna Daniele , Buglyó Péter , Bíró Linda , Micera Giovanni , Garribba Eugenio
Published: February 2012

The interaction of the VO2+ ion with pyrone derivatives and tropolone, which form very effective antidiabetic compounds, is critically re‐examined. The binary systems with ethylmaltol (Hema) and tropolone (Htrop) were studied in aqueous solution and in the solid state through the combined application of spectroscopic (EPR, UV/Vis and IR) and pH‐potentiometric techniques. The results were compared with those of the systems with maltol (Hma) and kojic acid (Hkoj) and rationalized on the basis of DFT simulations. All the ligands L– form [VOL]+, cis‐[VOL2(H2O)] and cis‐[VOL2(OH)]– species in aqueous solutions and a square‐pyramidal [VOL2] complex in the solid state, which transforms into cis‐[VOL2(solvent)] when it is dissolved in water or in a coordinating solvent. The coordinating properties of the ligands studied were compared with those of pyridinone [3‐hydroxy‐1,2‐dimethyl‐4(1H)pyridinone (Hdhp), and 1,2‐diethyl‐3‐hydroxy‐4(1H)pyridinone (Hdepp)] derivatives and catechol (H2cat), and were explained by postulating that from pyrones to pyridinones and to catechol the donor set changes progressively from (CO, O–) to (O–, O–). DFT calculations allowed us to determine the relative stability of the four possible structures (square pyramidal, trans‐ and two cis‐octahedral) of the bis‐chelated species and the aromaticity of the protonated, neutral and deprotonated form of the ligands through the calculation of the HOMA (harmonic oscillator model of aromaticity) index. The relationship between the electric charge on the oxygen donors, the mean distances and the difference between the lengths of C–Oket and C–Ophen bonds with (i) the pKa of the ligands, (ii) the pK of deprotonation of the equatorially coordinated water molecule in cis‐[VOL2(H2O)], and (iii) the 51V hyperfine coupling constant (Az) of [VOL2], cis‐[VOL2(H2O)] and cis‐[VOL2(OH)]– was also found and discussed.
Molecular Structure of a Hydridoniobocene Complex [Nb(η5‐C5H4SiMe3)2(H)3] and Its Use as Catalyst for the Ring‐Opening Polymerization of Cyclic Esters
Authors: Alonso‐Moreno Carlos , Antiñolo Antonio , García‐Martínez Joaquín C. , García‐Yuste Santiago , López‐Solera Isabel , Otero Antonio , Pérez‐Flores Juan C. , Tercero‐Morales Maria T.
Published: February 2012

The second polyhydridoniobocene complex that was characterized by X‐ray diffraction is reported. On the basis of H–H distances and H–Nb–H angles, [Nb(η5‐C5H4SiMe3)2(H)3] (1) is classified as a “compressed hydride”. Compound 1 acts as an efficient single‐component initiator for the ring‐opening polymerization of ϵ‐caprolactone and δ‐valerolactone. ϵ‐Caprolactone and δ‐valerolactone are both polymerized within a few hours to yield high‐to‐medium‐molecular‐weight polymers with medium to broad polydispersities. Polymer end‐group analysis showed that the polymerization proceeds through a coordination–insertion mechanism based on the cleavage of the ring between the oxygen atom and the acyl carbon atom.
Structure–Relaxivity Relationships among Targeted MR Contrast Agents
Authors: Caravan Peter , Zhang Zhaoda
Published: February 2012

Paramagnetic gadolinium(III) complexes are widely used to increase contrast in magnetic resonance (MR) images. Contrast enhancement depends on the concentration of the gadolinium complex and on its relaxivity, an inherent property of the complex. Increased relaxivity results in greater image contrast or the ability to detect the contrast agent at a lower concentration. An increase in the relaxivity enables the imaging of abundant molecular targets. Relaxivity depends on the structure of the complex, kinetics of inner‐sphere and second‐sphere water exchange, and on the rotational dynamics of the molecule. The latter, and in some cases the former, properties of the complex change when it is bound to its target. All of these properties can be rationally tuned to enhance relaxivity. In this Microreview, we summarize our efforts in understanding and optimizing the relaxivity of contrast agents targeted to serum albumin and to fibrin.
Activation of Gas‐Phase Uranyl Diacetone Alcohol Coordination Complexes by Spectator Ligand Addition
Authors: Rios Daniel , Gibson John K.
Published: February 2012

Gas‐phase addition of a basic ligand to dipositive uranyl coordination complexes comprising diacetone alcohol (DAA) results in water‐elimination, which indicates aldol dehydration of DAA to produce mesityl oxide. A novel attribute of the observed gas‐phase chemistry is that a ligand exothermically associates to a coordination complex to provide the excitation required to induce chemistry in other ligands, with the added “spectator ligand” remaining intact in the product. Dehydration of DAA was observed for addition of tetrahydrofuran, acetone, and 2‐propanol to uranyl complexes [UO2(DAA)2]2+ and [UO2(DAA)(acetone)2]2+. In contrast, [UO2(DAA)2(acetone)]2+ did not exhibit ligand‐addition chemistry, which is attributed to a high degree of coordinative saturation at the uranium metal center.
Preparation of New 1,4‐Diazocanes as Scaffolds for Combinatorial Chemistry
Authors: Penning Miriam , Christoffers Jens
Published: February 2012

Hexahydro‐2‐oxo‐1,4‐diazocin‐6‐carboxylic acid constitutes a conformationally rigid, crown‐shaped scaffold. An orthogonally protected (Boc at N‐4 and methyl ester at 6‐CO2H) representative was prepared by ring expansion of a 3‐pyrrolidone‐derived 1,4‐diketone with MeNH2. After deprotection, this building block was further diversified by reductive aminations and amidations and by sulfonamide and urea formation. Furthermore, the 6‐CO2H function was transformed into a 6‐NHCbz group in one step by carboxamide degradation in the presence of BnOH. An example of a cyclic tripeptoidic structure was synthesized by amidation with N‐Boc‐β‐alanine and glycine methyl ester. Structural features of the eight‐membered heterocycle were established by single‐crystal X‐ray structure analysis of a 4‐bromoaniline derivative.
Total Synthesis of (+)‐Aspicilin by an Alkyne‐Based Approach and Its Biological Evaluation
Authors: Raji Reddy Chada , Rao Nagavaram Narsimha , Sujitha Pombala , Kumar Chityal Ganesh
Published: February 2012

The stereoselective total synthesis of (+)‐aspicilin is described. The pivotal step in this approach is the generation of an enyne intermediate by the coupling of an alkyne with vinyl iodide, which constructed the C6–C7 bond. Conversion of the enyne to the desired macrolide was achieved through Sharpless asymmetric dihydroxylation and Yamaguchi macrolactonization as the key steps. Additionally, the biological activity of (+)‐aspicilin was evaluated on A549, HeLa, and MCF7 cancer cell lines.
Synthesis of Modified Phenylalanine Peptides by Cross Enyne Metathesis and a Diels–Alder Reaction as Key Steps
Authors: Kotha Sambasivarao , Goyal (née Bansal) Deepti , Thota Niranjan , Srinivas Venu
Published: February 2012

Modified phenylalanine‐based di‐ and tripeptides have been efficiently assembled by cross enyne metathesis and a Diels–Alder reaction as key steps under mild conditions. In all cases, peptide integrity was preserved, no racemisation was observed, and good yields of modified peptides were obtained.
Ti/Ni‐Based Multimetallic System for the Efficient Allylation of Carbonyl Compounds
Authors: Martínez‐Peragón Ángela , Millán Alba , Campaña Araceli G. , Rodríguez‐Márquez Irene , Resa Sandra , Miguel Delia , Álvarez de Cienfuegos Luis , Cuerva Juan M.
Published: February 2012

A mild method for the allylation of carbonyl compounds is presented. This methodology allows the allylation of a broad range of carbonyl compounds starting with allyl carbonates as pronucleophiles. Noteworthy is that ketones, infrequent substrates in other related protocols, are suitable substrates under these reaction conditions. Moreover, the reaction proceeds at room temperature with the use of catalytic amounts of both Ni and Ti catalysts. The success of this strategy is based on the perfect match between the late transition metal (nickel) and the radical reagent (titanium). The use of Ni instead of Pd widens the scope of this transformation and makes this method more economical.
Capillary electrophoretic analysis of whole blood samples for hemoglobin‐based oxygen carriers without the use of immunoprecipitation
Authors: Harrison Christopher R. , Vydha Srilatha
Published: February 2012

Hemoglobin‐based oxygen carriers (HBOCs) are blood substitutes, synthesized by polymerizing hemoglobin, which are being developed and investigated as alternatives to blood for medical purposes. However, due to their ability to increase the oxygen carrying capacity when taken by healthy individuals, HBOCs have been used as a doping agent among endurance athletes and are included in the World Anti‐Doping Agency's Prohibited List. To maintain the fairness of competitions and continue the battle against doping, it is essential to be able to detect HBOCs if present in an athlete's blood. To achieve this goal, it is necessary to differentiate HBOCs from the native hemoglobin and to do so in a cost and time effective manner. We have developed a rapid capillary zone electrophoresis (CZE), UV absorbance, method capable of detecting HBOCs, in whole blood samples, at levels below those considered necessary to provide a performance enhancement. Our approach to the analysis for HBOCs utilizes the whole blood sample, not just the plasma, and does not require the use of immunoprecipitants to ensure accurate analysis. By lysing the red blood cells and using centrifugal filtration, followed by our CZE separation, we are able to effectively distinguish between native hemoglobin and HBOCs. Through this method, we have been able to reliably detect concentrations of HBOCs at the equivalent of 5.5 g/L, the equivalent to a 3.5% increase in blood hemoglobin concentration for an athlete.
A facile electrophoretic technique to monitor phosphoenolpyruvate‐dependent kinases
Authors: Auger Christopher , Appanna Varun , Castonguay Zachary , Han Sungwon , Appanna Vasu D.
Published: February 2012

Phosphoenolpyruvate (PEP)‐dependent kinases are central to numerous metabolic processes and mediate the production of adenosine triphosphate (ATP) by substrate‐level phosphorylation (SLP). While pyruvate kinase (PK, EC: 2.7.1.40), the final enzyme of the glycolytic pathway is critical in the anaerobic synthesis of ATP from ADP, pyruvate phosphate dikinase (PPDK, EC: 2.7.9.1), and phosphoenolpyruvate synthase (PEPS, EC: 2.7.9.2) help generate ATP from AMP coupled to PEP as a substrate. Here we demonstrate an inexpensive and effective electrophoretic technology to determine the activities of these enzymes by blue‐native polyacrylamide gel electrophoresis (BN‐PAGE). The generation of pyruvate is linked to exogenous lactate dehydrogenase (LDH), and the oxidation of reduced nicotinamide adenine dinucleotide (NADH) coupled to 2,6‐dichloroindophenol (DCIP) and iodonitrotetrazolium chloride (INT) results in a formazan precipitate which is easily quantifiable. The selectivity of the enzymes is ensured by including either AMP or ADP and pyrophosphate (PPi) or inorganic phosphate (Pi). Activity bands were readily obtained after incubation in the respective reaction mixtures for 20–30 min. Cell‐free extract concentrations as low as 20 μg protein equivalent yielded activity bands and substrate levels were manipulated to optimize sensitivity of this analytical technique. High‐pressure liquid chromatography (HPLC), two‐dimensional (2‐D) SDS‐PAGE (where SDS is sodium dodecyl sulfate), and immunoblot studies of the excised activity band help further characterize these PEP‐dependent kinases. Furthermore, these enzymes were readily identified on the same gel by incubating it sequentially in the respective reaction mixtures. This technique provides a facile method to elucidate these kinases in biological systems.
A polymorphism in a let‐7 microRNA binding site of KRAS in women with endometriosis
Authors: Grechukhina Olga , Petracco Rafaella , Popkhadze Shota , Massasa Efi , Paranjape Trupti , Chan Elcie , Flores Idhaliz , Weidhaas Joanne B. , Taylor Hugh S.
Published: February 2012

Endometriosis is found in 5–15% of women of reproductive age and is more frequent in relatives of women with the disease. Activation of KRAS results in de novo endometriosis in mice, however, activating KRAS mutations have not been identified in women. We screened 150 women with endometriosis for a polymorphism in a let‐7 microRNA (miRNA) binding site in the 3'‐UTR of KRAS and detected a KRAS variant allele in 31% of women with endometriosis as opposed to 5% of a large diverse control population. KRAS mRNA and protein expression were increased in cultured endometrial stromal cells of women with the KRAS variant. Increased KRAS protein was due to altered miRNA binding as demonstrated in reporter assays. Endometrial stromal cells from women with the KRAS variant showed increased proliferation and invasion. In a murine model, endometrial xenografts containing the KRAS variant demonstrated increased proliferation and decreased progesterone receptor levels. These findings suggest that an inherited polymorphism of a let‐7 miRNA binding site in KRAS leads to abnormal endometrial growth and endometriosis. The LCS6 polymorphism is the first described genetic marker of endometriosis risk.
Influence of Attitudes towards Change and Self‐directness on Dropout in Eating Disorders: A 2‐Year Follow‐up Study
Authors: Rodríguez‐Cano Teresa , Beato‐Fernandez Luis , Moreno Luis Rojo , Vaz Leal Francisco J.
Published: February 2012

Objective

This study examined dropout‐related factors at the Outpatient Eating Disorders Treatment Programme.

Method

One hundred ninety‐six eating disorders patients following DSM‐IV diagnostic criteria that consecutively commenced treatment were recruited and followed up for a 2‐year period. A total of 151 patients completed the whole assessment with a set of questionnaires evaluating eating and general psychopathology. The Attitudes towards Change in Eating Disorders questionnaire was used, and personality was evaluated using the Temperament and Character Inventory. During the follow‐up period, patients were re‐assessed. Two years later, 102 patients continued on treatment.

Results

Scores on Precontemplation at the beginning were predictors for dropout at 2‐year follow‐up. Character variables, as Responsibility, Integrity and Self‐acceptance were protective factors to be at Precontemplation stage.

Discussion

The clinician's challenge is to help eating disorders patients to develop an unyielding sense of responsibility and self‐acceptance, aimed to integrate the therapeutic choice into their own intrapersonal frame of goals. Copyright © 2012 John Wiley & Sons, Ltd and Eating Disorders Association.
European Miocene Hominids and the Origin of the African Ape and Human Clade
Authors: Begun David R. , Nargolwalla Mariam C. , Kordos László
Published: February 2012

In 1871, Darwin famously opined, “In each great region of the world the living mammals are closely related to the extinct species of the same region. It is therefore probable that Africa was formerly inhabited by extinct apes closely allied to the gorilla and chimpanzee; and as these two species are now man's nearest allies, it is somewhat more probable that our early progenitors lived on the African continent than elsewhere.”1 Although this quote is frequently recalled today, Darwin's next line is rarely acknowledged: “But it is useless to speculate on this subject, for an ape nearly as large as a man, namely the Dryopithecus of Lartet, which was closely allied to the anthropomorphous Hylobates, existed in Europe during the Upper Miocene period; and since so remote a period the earth has certainly undergone many great revolutions, and there has been ample time for migration on the largest scale.”1
Valuing Seller‐Defaultable Options
Authors: Lu Jin‐Ray , Chen Yi‐Chun , Hwang Chih‐Chiang , Ting Yi‐Chun
Published: February 2012

This study analyzes seller‐defaultable options that allow option writers to have a free‐will right to default, along with some prespecified default mechanisms. We analytically and numerically examine the pricing, hedging, defaulting, and profitability of the seller‐defaultable options, considering three possible scenarios for seller default. Analyzing the essential implications of seller‐defaultable options, we show that the option price is positively correlated with the default fine, underlying asset price, and volatility. The seller‐defaultable option's Greeks appear more complicated than those of the plain vanilla options. The likelihood of sellers defaulting increases with the underlying asset price, interest rate, volatility, and maturity time. Subject to the default mechanism, the buyers’ trading involves a trade‐off between profits and costs. © 2012 Wiley Periodicals, Inc. Jrl Fut Mark 33:129–157, 2013
Somatic mutations in the notch, NF‐KB, PIK3CA, and hedgehog pathways in human breast cancers
Authors: Jiao Xiang , Wood Laura D. , Lindman Monica , Jones Sian , Buckhaults Phillip , Polyak Kornelia , Sukumar Saraswati , Carter Hannah , Kim Dewey , Karchin Rachel , Sjöblom Tobias
Published: February 2012

Exome sequencing of human breast cancers has revealed a substantial number of candidate cancer genes with recurring but infrequent somatic mutations. To determine more accurately their mutation prevalence, we performed a mutation analysis of 36 novel candidate cancer genes in 96 human breast cancers. Somatic mutations with potential impact on protein function were observed in the genes ADAM12, CENTB1, CENTG1, DIP2C, GLI1, GRIN2D, HDLBP, IKBKB, KPNA5, NFKB1, NOTCH1, and OTOF. These findings strengthen the evidence for involvement of the Notch, Hedgehog, NF‐KB, and PIK3CA pathways in breast cancer development, and point to novel processes that likely are involved. © 2012 Wiley Periodicals, Inc.
Time to get off the fence: The need for definitive international guidance on statistical analysis of ecotoxicity data
Authors: van Dam Rick A , Harford Andrew J , Warne Michael St J
Published: February 2012

The use of the no observed effect concentration (NOEC) and lowest observed effect concentration (LOEC) in ecotoxicology has been consistently criticized for over 30 years. A search of the literature from the past 30 years found 22 articles challenging the validity and/or appropriateness of NOEC/LOEC data compared to only one in defense of such data. Notwithstanding this compelling weight of evidence, the NOEC and LOEC remain commonly published measures of toxicity from ecotoxicological studies. In this article we argue that the major reason for the continued generation and publication of NOEC/LOEC data is that key government and intergovernmental organizations have been “sitting on the fence” on the issue for more than a decade. Although most key environmental quality guideline, toxicity testing, and associated guidance documents have now recognized the limitations of NOEC/LOEC data, to date no such document or standard toxicity test method has formally ceased recommending or providing guidance on the generation of such data. This is a problem because it is these very guidance documents and test methods that regulatory agencies demand be used by industry for regulatory activities, and on which commercial testing facilities attain and maintain their testing accreditation. Consequently, there will be little impetus for change to statistical analysis practices unless changes to the key guidance documents and test methods necessitate it. Although some progress on this has been made (e.g., in Canada, Australia and New Zealand), there needs to be stronger and universal action to ensure NOEC/LOEC data are no longer generated. Integr Environ Assess Manag 2012; 8: 242–245. © 2012 SETAC
Multipotent progenitors resident in the skeletal muscle interstitium exhibit robust BMP-dependent osteogenic activity and mediate heterotopic ossification
Authors: Wosczyna Michael N , Biswas Arpita A , Cogswell Catherine A , Goldhamer David J
Published: February 2012

Heterotopic ossification is a debilitating condition that can result from traumatic injury, surgery, or genetic disease. We investigated the cellular origins of heterotopic skeletogenesis in the mouse using lineage tracing and bioassays of heterotopic ossification based on intramuscular transplantation. We identified, characterized, and purified a tissue-resident stem/progenitor cell population that exhibits robust osteogenic potential and represents a major cell-of-origin for heterotopic ossification. These progenitors reside in the interstitium of skeletal muscle and other tissues, and are distinct from the endothelium, which does not exhibit osteogenic activity in response to bone morphogenetic protein 2 (BMP2) stimulation. Intramuscular transplantation, together with clonal analysis in culture, revealed that these progenitors are multipotent, exhibiting the capacity for both BMP-dependent skeletogenic differentiation and spontaneous adipogenic differentiation. Identifying the cells-of-origin responsible for heterotopic ossification provides a potential therapeutic target to treat, mitigate, or prevent this disabling condition. © 2012 American Society for Bone and Mineral Research.
Effect of vertebroplasty on pain relief, quality of life, and the incidence of new vertebral fractures: A 12-month randomized follow-up, controlled trial
Authors: Blasco Jordi , Martinez-Ferrer Angeles , Macho Juan , San Roman Luis , Pomés Jaume , Carrasco Josep , Monegal Ana , Guañabens Nuria , Peris Pilar
Published: February 2012

Uncertainty regarding the benefits of vertebroplasty (VP) for the treatment of acute osteoporotic vertebral fractures has recently arisen. A prospective, controlled, randomized single-center trial (ClinicalTrials.gov registration number NCT00994032) was designed to compare the effects of VP versus conservative treatment on the quality of life and pain in patients with painful osteoporotic vertebral fractures, new fractures and secondary adverse effects were also analyzed during a 12-month follow-up period. A total of 125 patients were randomly assigned to receive conservative treatment or VP. The primary end point was to compare the evolution of the quality of life (Quality of Life Questionnaire of the European Foundation for Osteoporosis [Qualeffo-41] and pain (Visual Analogue Scale [VAS]) during a 12 month follow-up. Secondary outcomes included comparison of analgesic consumption, clinical complications, and radiological vertebral fractures at the same time points. Both arms showed significant improvement in VAS scores at all time points, with greater improvement (p = 0.035) in the VP group at the 2-month follow-up. Significant improvement in Qualeffo total score was seen in the VP group throughout the study, whereas this was not seen in the conservative treatment arm until the 6-month follow-up. VP treatment was associated with a significantly increased incidence of vertebral fractures (odds ratio [OR], 2 · 78; 95% confidence interval [CI], 1.02–7.62, p = 0.0462). VP and conservative treatment are both associated with significant improvement in pain and quality of life in patients with painful osteoporotic vertebral fractures over a 1-year follow-up period. VP achieved faster pain relief with significant improvement in the pain score at the 2-month follow-up but was associated with a higher incidence in vertebral fractures. © 2012 American Society for Bone and Mineral Research.
Therapeutic plasma exchange in Streptococcus pneumoniae‐associated hemolytic uremic syndrome: A case report
Authors: Petras Melissa L. , Dunbar Nancy M. , Filiano James J. , Braga Matthew S. , Chobanian Michael C. , Szczepiorkowski Zbigniew M.
Published: February 2012

Streptococcus pneumoniae‐associated hemolytic uremic syndrome (pHUS) is an atypical form of HUS associated with microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. Although less common than diarrhea‐associated HUS, incidence appears to be increasing. We report a case of a child with pHUS who underwent a course of therapeutic plasma exchange (TPE) and had complete recovery. This report adds to the existing literature supporting TPE in cases of pHUS. J. Clin. Apheresis, 2012. © 2012 Wiley Periodicals, Inc.
The relationships between snail1 and estrogen receptor signaling in breast cancer cells
Authors: Scherbakov Alexander M. , Andreeva Olga E. , Shatskaya Valentina A. , Krasil'nikov Mikhail A.
Published: February 2012

The loss of hormonal dependency of breast tumor cells is often accompanied with the appearance of epithelial‐mesenchymal transition (EMT) features and increase in cell metastasis and invasiveness. The central role in the EMT belongs to transcription factors Snail responded for the decrease in E‐cadherin expression and cell contacts, stimulation of cell mobility and invasiveness. Aim was to study the relationships between estrogen receptor machinery and Snail1 signaling, and mechanism of Snail1 regulation in hormone‐resistant breast cancer cells. The experiments were performed on the estrogen‐dependent MCF‐7 breast cancer cells, estrogen‐hyposensitive MCF‐7/LS subline generated through long‐term cultivation of the parental cells in steroid‐free medium, and ER‐negative estrogen‐resistant HBL‐100 cells. Snail1, estrogen receptor, p65 NF‐κB, E‐cadherin levels were analyzed by Western blot. We found that decrease in the estrogen dependency is correlated with increase in Snail1 expression and activity, we demonstrated the Snail1 involvement in the negative regulation of ER, and showed that Snail1 inhibition partially restores the sensitivity of the estrogen‐hyposensitive cells to antiestrogen tamoxifen. Furthermore, NF‐κB was found to serve as a positive regulator of Snail1 in breast cancer cells, and simultaneous inhibition of NF‐κB and Snail1 resulted in additional increase in cell response to tamoxifen. In general, the results obtained demonstrate the phenomenon of Snail1 activation in the hormone‐resistant breast cancer cells, and show that Snail1 and NF‐κB may serve as an important targets in the treatment of breast cancer, both estrogen‐dependent and estrogen‐independent tumors. J. Cell. Biochem. 113: 2147–2155, 2012. © 2012 Wiley Periodicals, Inc.
Phenotypic characterization of transgenic mice harboring Nf1+/− or Nf1−/− osteoclasts in otherwise Nf1+/+ background
Authors: Alanne Maria H. , Siljamäki Elina , Peltonen Sirkku , Väänänen Kalervo , Windle Jolene J. , Parada Luis F. , Määttä Jorma A. , Peltonen Juha
Published: February 2012

Skeletal abnormalities in neurofibromatosis type 1 syndrome (NF1) are observed in ∼50% of patients. Here, we describe the phenotype of Nf1Ocl mouse model with Nf1‐deficient osteoclasts. Nf1Ocl mice with Nf1+/− or Nf1−/− osteoclasts in otherwise Nf1+/+ background were successfully generated by mating parental Nf1flox/flox and TRAP‐Cre mice. Contrary to our original hypothesis, osteoporotic or fragile bone phenotype was not observed. The µCT analysis revealed that tibial bone marrow cavity, trabecular tissue volume, and the perimeter of cortical bone were smaller in Nf1 mice compared to Nf1 control mice. Nf1 mice also a displayed narrowed growth plate in the proximal tibia. In vitro analysis showed increased bone resorption capacity and cytoskeletal changes including irregular cell shape and abnormal actin ring formation in Nf1−/− osteoclasts. Surprisingly, the size of spleen in Nf1 mice was two times larger than in controls and histomorphometric analysis showed splenic megakaryocytosis. In summary, Nf1Ocl mouse model presented with a mild but specific bone phenotype. This study shows that NF1‐deficiency in osteoclasts may have a role in the development of NF1‐related skeletal abnormalities, but Nf1‐deficiency in osteoclasts in Nf1+/+ background is not sufficient to induce skeletal abnormalities analogous to those observed in patients with NF1. J. Cell. Biochem. 113: 2136–2146, 2012. © 2012 Wiley Periodicals, Inc.
HDAC2 overexpression confers oncogenic potential to human lung cancer cells by deregulating expression of apoptosis and cell cycle proteins
Authors: Jung Kwang Hwa , Noh Ji Heon , Kim Jeong Kyu , Eun Jung Woo , Bae Hyun Jin , Xie Hong Jian , Chang Young Gyoon , Kim Min Gyu , Park Hanna , Lee Jung Young , Nam Suk Woo
Published: February 2012

Histone deacetylase 2 (HDAC2) is crucial for embryonic development, affects cytokine signaling relevant for immune responses, and is often significantly overexpressed in solid tumors, but little is known of its role in human lung cancer. In this study, we demonstrated the aberrant expression of HDAC2 in lung cancer tissues and investigated oncogenic properties of HDAC2 in human lung cancer cell lines. HDAC2 inactivation resulted in regression of tumor cell growth and activation of cellular apoptosis via p53 and Bax activation and Bcl2 suppression. In cell cycle regulation, HDAC2 inactivation caused induction of p21WAF1/CIP1 expression, and simultaneously suppressed the expressions of cyclin E2, cyclin D1, and CDK2, respectively. Consequently, this led to the hypophosphorylation of pRb protein in G1/S transition and thereby inactivated E2F/DP1 target gene transcriptions of A549 cells. In addition, we demonstrated that HDAC2 directly regulated p21WAF1/CIP1 expression in a p53‐independent manner. However, HDAC1 was not related to p21WAF1/CIP1 expression and tumorigenesis of lung cancer. Lastly, we observed that sustained‐suppression of HDAC2 in A549 lung cancer cells attenuated in vitro tumorigenic properties and in vivo tumor growth of the mouse xenograft model. Taken together, we suggest that the aberrant regulation of HDAC2 and its epigenetic regulation of gene transcription in apoptosis and cell cycle components play an important role in the development of lung cancer. J. Cell. Biochem. 113: 2167–2177, 2012. © 2012 Wiley Periodicals, Inc.
Core–shell potential‐derived point charges
Authors: Tan Jeffrey S. , Boerrigter Stephan X. M. , Scaringe Raymond P. , Morris Kenneth R.
Published: February 2012

The present work details the development of a core‐shell model for the purposes of obtaining potential‐derived point charges from the ab initio molecular electrostatic potential. In contrast to atomic point charge models, the core‐shell model decomposes all atoms into a core with static charge located at a fixed atomic position and a shell with variable charge and position. The optimization of shell charges and positions is discussed. The core‐shell model was found to significantly improve description of the ab initio electrostatic potential when compared to potential‐derived net atomic point charge models as well as distributed multipoles with contributions up to atomic quadrupole moments. The core‐shell model was found to produce similar results as the Weller‐Williams lone‐pair model and differences in the implementation of the models are discussed. © 2012 Wiley Periodicals, Inc. J Comput Chem, 2012
Mental Health Implications of Human Attachment to Companion Animals
Authors: Peacock Jasmin , Chur‐Hansen Anna , Winefield Helen
Published: February 2012

Objectives

Because of the contradictory nature of findings and methodological weaknesses identified within current human‐companion animal bond research, there is a need to further explore the connection between human‐animal bonds and mental health.

Design

The purpose of this survey questionnaire study was to explore the relationship of attachment to companion animal and human psychological distress after controlling for demographic variables, and to investigate whether the relationship between social supports and psychological distress would be moderated by attachment to a companion animal.

Results

Results highlight the psychological vulnerability of individuals reporting a strong bond with their companion animal.

Conclusions

These findings are discussed in terms of their implications for mental health services designed to anticipate and address client‐related companion animal needs.
The Factor Structure and Concurrent Validity of the Korean Version of the Metacognitions Questionnaire 30 (K‐MCQ‐30)
Authors: Cho Yongrae , Jahng Seungmin , Chai Sukhi
Published: February 2012

Objectives

We aimed to examine the factor structure of a Korean version of the Metacognitions Questionnaire 30 (K‐MCQ‐30) and to further evaluate its concurrent validity.

Method

Confirmatory factor analyses were conducted on the data sets from two independent samples of Korean college students (n = 662; n = 664). Correlation and multiple regression analyses were conducted on the cross‐sectional data from another sample (n = 97).

Results

The 5‐factor model of the K‐MCQ‐30 showed a good fit to the first sample after minor modification. The revised 5‐factor model was replicated with the second sample. Five factors of the K‐MCQ‐30 had positive correlations with measures of emotional disorder symptoms and predicted each of the symptoms in different ways.

Conclusions

These results provide general support for the 5‐factor structure of the K‐MCQ‐30 and its good concurrent validity in nonclinical samples.
Public Speaking in Social Phobia: A Pilot Study of Self‐Ratings and Observers' Ratings of Social Skills
Authors: Levitan Michelle Nigri , Falcone Eliane Mary , Placido Monique , Krieger Stephanie , Pinheiro Layse , Crippa Jose Alexandre , Bruno Leandro Marchetti , Pastore Daniele , Hallak Jaime , Nardi Antonio Egidio
Published: February 2012

Objectives

The aim of this pilot study was to investigate whether patients with social anxiety disorder (SAD) differ from controls in the quality of skill‐related behaviors displayed during a speech and in overall behavioral adequacy as perceived by observers and by the patients themselves.

Design

A total of 18 SAD patients and 18 controls were screened by a diagnostic interview and took part in a 3‐minute speech of their own choosing. For each videotaped speech, observers rated the adequacy of the skill‐related behaviors and overall performance adequacy. After the experiment, participants were asked to rate their own overall performance adequacy.

Results

The results showed that SAD patients exhibited significantly worse voice intonation and fluency of the speech, however no differences were found in global self‐ratings. Moreover, the performance evaluations of the SAD group were consistent with the observers, while the controls evaluated their performance lower than the observers.

Conclusions

The results are inconsistent with the cognitive model, because patients with SAD did not underestimate their performance. Compared with spontaneous interactions, the clear rules established for such social situations as speeches may result in less cognitive distortion for SAD patients.
A Comparison of Three Theoretically Important Constructs: What Accounts For Symptoms of Borderline Personality Disorder?
Authors: Cheavens Jennifer S. , Strunk Daniel R. , Chriki Lyvia
Published: February 2012

Objective

Theories point to different mechanisms through which borderline personality disorder (BPD) symptoms may be developed and maintained: (a) emotion regulation dysfunction, (b) problematic relations, and (c) nonintegrated self. However, researchers have not investigated the relative contribution of these mechanisms simultaneously in accounting for the variance observed in BPD symptoms.

Method

Drawing from university students and Internet users, 462 adults (63% female, 77% Caucasian) completed self‐report measures of emotion regulation, interpersonal problems, sense of self, BPD symptoms, and depressive symptoms.

Results

All predictors were independently associated with BPD symptoms, with emotion regulation difficulties having the strongest relation. For high BPD individuals (N = 94), emotional regulation difficulties was the only predictor uniquely associated with BPD symptoms and interpersonal problems was the sole unique predictor of depressive symptoms.

Conclusion

These results suggest that emotion regulation difficulties and interpersonal problems may be particularly problematic for those with high BPD symptoms in different ways. Implications and future directions are discussed.
Estimating WAIS‐IV Indexes: Proration Versus Linear Scaling in a Clinical Sample
Authors: Umfleet Laura Glass , Ryan Joseph J. , Gontkovsky Sam T. , Morris Jeri
Published: February 2012

Objectives

We compared the accuracy of proration and linear scaling for estimating Wechsler Adult Intelligence Scale–Fourth Edition (WAIS‐IV), Verbal Comprehension Index (VCI), and Perceptual Reasoning Index (PRI) composites from all possible two subtest combinations. The purpose was to provide practice relevant psychometric results in a clinical sample.

Design

The present investigation was an archival study that used mostly within‐group comparisons. We analyzed WAIS‐IV data of a clinical sample comprising 104 patients with brain damage and 37 with no known neurological impairment.

Results

In both clinical samples, actual VCI and PRI scores were highly correlated with estimated index scores based on proration and linear scaling (all rs ≥.95). In the brain‐impaired sample, significant mean score differences between the actual and estimated composites were found in two comparisons, but these differences were less than three points; no other significant differences emerged.

Conclusions

Overall, findings demonstrate that proration and linear scaling methods are feasible procedures when estimating actual Indexes. There was no advantage of one computational method over the other.
Myeloid Elf‐1‐like factor stimulates adipogenic differentiation through the induction of peroxisome proliferator‐activated receptor γ expression in bone marrow
Authors: Baek Kyunghwa , Cho Je‐Yoel , Hwang Hyo Rin , Kwon Arang , Lee Hye‐Lim , Park Hyun‐Jung , Qadir Abdul S. , Ryoo Hyun‐Mo , Woo Kyung Mi , Baek Jeong‐Hwa
Published: February 2012

Myeloid Elf‐1 like factor (MEF) is one of the Ets transcription factors known to regulate cell proliferation and differentiation. A previous report has shown that osteoblast‐specific MEF transgenic mice (Col1a1‐MEF TG mice) have low bone mass but high bone marrow adiposity. In the present study, we explored a previously unappreciated mechanism whereby MEF promotes adipogenesis in bone marrow. An adipogenic colony‐forming unit assay showed that bone marrow cells derived from Col1a1‐MEF TG mice had a higher adipogenic differentiation potential compared to those from wild‐type. The levels of adipogenic marker genes expression in 3T3L1 cells were higher when co‐cultured with Col1a1‐MEF TG bone marrow cells than with wild‐type cells. MC3T3‐E1 preosteoblasts transfected with MEF secreted higher levels of 15‐deoxy‐delta (12, 14)‐prostaglandin J2, a potent endogenous ligand of peroxisome proliferator‐activated receptor γ (PPARγ), under adipogenic conditions. MEF overexpression increased the adipogenic marker genes expression including PPARγ and lipid droplet accumulation in MC3T3‐E1 preosteoblasts and 3T3L1 preadipocytes. Endogenous MEF expression levels increased as adipocyte differentiation proceeded. Knockdown of MEF by siRNA suppressed expression levels of adipogenic marker genes including PPARγ. MEF directly bound to the MEF binding element on the mouse PPARγ promoter, transactivating promoter activity. Immunohistochemical staining of tibia sections demonstrated that bone lining cells and bone marrow cells express higher levels of PPARγ protein in Col1a1‐MEF TG mice than in wild‐type mice. These results suggest that MEF transactivates PPARγ expression, which, in turn, enhances adipogenic differentiation. Furthermore, MEF overexpressing osteoblasts secrete higher levels of adipogenic factors, creating a marrow microenvironment that favors adipogenesis. J. Cell. Physiol. 227: 3603–3612, 2012. © 2012 Wiley Periodicals, Inc.
Ischemic tolerance in the brain: Endogenous adaptive machinery against ischemic stress
Authors: Kitagawa Kazuo
Published: February 2012

Although more than 100 drugs have been examined clinically, tissue plasminogen activator remains the only drug approved for the treatment of acute ischemic stroke. Since the discovery of ischemic tolerance, it has been widely recognized that the brain possesses an endogenous protective machinery to protect against ischemic stress. Recent studies have clarified that both the upregulation of neuroprotective signaling and the downregulation of inflammatory or apoptotic pathways are involved equally in the acquisition of ischemic tolerance. The triggering stimuli for ischemic stresses are divided into hypoxic, oxidant/inflammatory, and glutamate stress. Glutamate stress, particularly the synaptic stimulation of the N‐methyl‐D‐aspartate receptor, leads to activation of the cAMP response element‐binding protein, which could subsequently induce gene expression of several neuroprotective molecules. Gene reprogramming and metabolic downregulation are intimately involved in ischemic tolerance as well as in hibernation and hypothermia. Micro‐RNAs may be a key player for tuning the level of gene expression in ischemic tolerance. Future research should be performed to investigate the most effective combination for brain protection, enhancement of cell survival signaling, and inhibition of the inflammatory or apoptotic pathways. © 2012 Wiley Periodicals, Inc.
Cellular mechanisms of plasmalemmal sealing and axonal repair by polyethylene glycol and methylene blue
Authors: Spaeth C.S. , Robison T. , Fan J.D. , Bittner G.D.
Published: February 2012

Mammalian neurons and all other eukaryotic cells endogenously repair traumatic injury within minutes by a Ca2+‐induced accumulation of vesicles that interact and fuse with each other and the plasmalemma to seal any openings. We have used uptake or exclusion of extracellular fluorescent dye to measure the ability of rat hippocampal B104 cells or rat sciatic nerves to repair (seal) transected neurites in vitro or transected axons ex vivo. We report that endogenous sealing in both preparations is enhanced by Ca2+‐containing solutions and is decreased by Ca2+‐free solutions containing antioxidants such as dithiothreitol (DTT), melatonin (MEL), methylene blue (MB), and various toxins that decrease vesicular interactions. In contrast, the fusogen polyethylene glycol (PEG) at 10–50 mM artificially seals the cut ends of B104 cells and rat sciatic axons within seconds and is not affected by Ca2+ or any of the substances that affect endogenous sealing. At higher concentrations, PEG decreases sealing of transected axons and disrupts the plasmalemma of intact cells. These PEG‐sealing data are consistent with the hypothesis that lower concentrations of PEG directly seal a damaged plasmalemma. We have considered these and other data to devise a protocol using a well‐specified series of solutions that vary in tonicity, Ca2+, MB, and PEG content. These protocols rapidly and consistently repair (PEG‐fuse) rat sciatic axons in completely cut sciatic nerves in vivo rapidly and dramatically to restore long‐lasting morphological continuity, action potential conduction, and behavioral functions. © 2012 Wiley Periodicals, Inc.
Evidence for climatic variability and its impact on human development during the Neolithic from Loughmeenaghan, County Sligo, Ireland
Authors: Stolze Susann , Dörfler Walter , Monecke Thomas , Nelle Oliver
Published: February 2012

High‐resolution pollen and geochemical analyses conducted on a sediment profile from a small lake in County Sligo, Ireland, revealed that human development during the Neolithic was influenced by pronounced climatic oscillations. The primeval woodland around the lake experienced a considerable transformation coinciding with the elm decline at 3810 BC. The subsequent increase in summer temperatures and decrease in precipitation favoured wheat cultivation in the lake's catchment area, which was practised for approximately 140 years. A shift towards pastoral farming took place with the establishment of exceptionally dry conditions between 3650 and 3560 BC, when lake level and influx of allochthonous material were notably low. The onset of cool and wet conditions at the transition from the Early to Middle Neolithic possibly caused the initial decline of human activity in the area. Periods of particularly high precipitation during the Middle and early Late Neolithic contributed to the abandonment of the area by the first farmers. Comparison of the proxy record from the study site with other palynological and archaeological records from Ireland suggests that climatic variability on the decadal to centennial scale represented a primary control on the nature and duration of farming practices during the Neolithic. Copyright © 2012 John Wiley & Sons, Ltd.
Angiotensin‐converting enzyme inhibitory and antioxidative activities and functional characterization of protein hydrolysates of hard‐to‐cook chickpeas
Authors: Medina‐Godoy Sergio , Ambriz‐Pérez Dulce L , Fuentes‐Gutiérrez Cindy I , Germán‐Báez Lourdes J , Gutiérrez‐Dorado Roberto , Reyes‐Moreno Cuauhtémoc , Valdez‐Ortiz Angel
Published: February 2012

BACKGROUND: The potential use of hard‐to‐cook (hardened) chickpeas to obtain value‐added functional food ingredients was evaluated. For that purpose, some nutraceutical and functional attributes of several chickpea protein hydrolysates (CPHs) prepared from both fresh and hard‐to‐cook grains were evaluated.

RESULTS: All the CPHs prepared from both fresh and hard‐to‐cook grains, with the enzymes alcalase, pancreatin and papain, showed high angiotensin converting enzyme inhibitory (ACE‐I) activity with IC50 values ranging from 0.101 to 37.33 µg mL−1; similarly, high levels of antioxidant activity (around 18.17–95.61 µmol Trolox equivalent antioxidant capacity µg−1 CPH) were obtained through both the 2,2‐diphenyl‐1‐picrylhydrazyl and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) methods. Regarding functional characterization of the CPHs, oil absorption values ranged from 1.91 to 2.20 mL oil g−1 CPH, with water solubility almost 100% from pH 7 to 10.

CONCLUSION: The high antioxidant and ACE‐I activities as well as the good functional properties of the CPH prepared from both fresh and hard‐to‐cook grains, suggest its use in food formulations with value added in human health. Copyright © 2012 Society of Chemical Industry