bluuebunny/crossref_metadata_2025 huggingface dataset:
Catalytic Reaction Mechanism of Mn‐Doped Nanoporous Aluminophosphates for the Aerobic Oxidation of Hydrocarbons
Authors: Gómez‐Hortigüela Luis , Corà Furio , Sankar Gopinathan , Zicovich‐Wilson Claudio M. , Catlow C. Richard A.
Published: November 2010

In this work we apply state‐of‐the‐art electronic‐structure‐based computational methods based on hybrid‐exchange density functional theory to study the mechanism of the aerobic oxidation of hydrocarbons catalysed by Mn‐doped nanoporous aluminophosphates (Mn‐AlPOs). We compare our results with available experimental data. We show that the catalytic efficiency of Mn‐AlPOs in oxidation reactions is intrinsically linked to 1) the Mn redox activity, in particular between 2+ and 3+ oxidation states, and 2) the coordinative insaturation of tetrahedral Mn embedded in AlPO frameworks, which facilitates the reaction by stabilising oxo‐type radicals through the formation of Mn complexes. Our mechanism demonstrates the crucial role of both MnIII and MnII in the reaction mechanism: MnIII sites undergo an initial reaction cycle that leads to the production of the alkyl hydroperoxide intermediate, which can only be transformed into the oxidative products (alcohol, aldehyde and acid) by MnII. A preactivation step is required to yield the reduced MnII sites able to decompose the hydroperoxide intermediates; this step takes place through a transformation of the hydrocarbon into the corresponding peroxo‐derivative, stabilised by forming a complex with MnIII and yielding at the same time reduced MnII sites. Both species enter a subsequent propagation cycle in which MnII catalyses the dissociation of the hydroperoxide that proceeds until the formation of the oxidative products by two parallel pathways, through alkoxy‐ or hydroxy‐radical‐like intermediates, whilst the MnIII–peroxo complex enables further production of the hydroperoxide intermediate.
The Iron‐Related Molecular Toxicity Mechanism of Synthetic Asbestos Nanofibres: A Model Study for High‐Aspect‐Ratio Nanoparticles
Authors: Turci Francesco , Tomatis Maura , Lesci Isidoro G. , Roveri Norberto , Fubini Bice
Published: November 2010

Asbestos shares with carbon nanotubes some morphological and physico‐chemical features. An asbestos‐like behaviour has been recently reported by some authors, though the mechanism of toxicity may be very different. To identify at the atomic level the source of toxicity in asbestos, the effect of progressive iron loading on a synthetic iron‐free model nanofibre previously found non‐toxic in cellular tests was studied. A set of five synthetic chrysotile nanofibres [(Mg,Fe)3(Si2O5)(OH)4] has been prepared with Fe ranging from 0 to 1.78 wt %. The relationship between fibre‐induced free‐radical generation and the physico‐chemical characteristics of iron active sites was investigated with spin‐trapping techniques on an aqueous suspension of the fibres and Mössbauer and EPR spectroscopies on the solids, respectively. The fully iron‐free fibre was inert, whereas radical activity arose with even the smallest amount of iron. Surprisingly, such activity decreased upon increasing iron loading. Mössbauer and EPR revealed isolated iron ions in octahedral sites that undergo both axial and rhombic distortion and the occurrence of aggregated iron ions and/or extra‐framework clustering. The isolated ions largely prevailed at the lowest loadings. Upon increasing the loading, the amount of isolated iron was reduced and the aggregation increased. A linear relationship between the formation of carbon‐centred radicals and the amount of rhombic‐distorted isolated iron sites was found. Even the smallest iron contamination imparts radical reactivity, hence toxicity, to any chrysotile outcrop, thereby discouraging the search for non‐toxic chrysotile. The use of model solids that only differ in one property at a time appears to be the most successful approach for a molecular understanding of the physico‐chemical determinants of toxicity. Such findings could also be useful in the design of safer nanofibres.
Indoline‐3‐Carboxylic Acid Derived Organocatalysts for the anti‐Mannich Reaction
Authors: Pietruszka Jörg , Simon Robert Christian
Published: November 2010

Mannich type reactions of a preformed aldimine with various carbonyl compounds were investigated with a series of functionalised indoline derivatives as catalysts: indoline‐3‐carboxylic acid, the diphenylcarbinol analogue and O‐protected silyl ether analogues. All compounds were readily prepared in enantiopure form by using an enzymatic kinetic resolution as a key step (E≫100). The alcohol and ether catalysts failed to induce complete chirality transfer but did afford the Mannich bases in good yields and high diastereomeric ratios, whereas the acid catalyst gave the products in a highly diastereo‐ and enantioselective manner. The absolute configuration of the products was determined by a syn–anti isomerisation protocol, initiated by the sterically demanding base 1,8‐diazabicyclo[5.4.0]undec‐7‐ene.
Oriented Free‐Standing Ammonium Vanadium Oxide Nanobelt Membranes: Highly Selective Absorbent Materials
Authors: Zou Rujia , Zhang Zhenyu , Yu Li , Tian Qiwei , Wu Jianghong , Sun Yangang , Chen Zhigang , Hu Junqing
Published: November 2010

Highly selective, absorbent, free‐standing, paper‐like membranes made of ammonium vanadium oxide (NH4V4O14) nanobelts have been engineered by taking advantage of the nanoscaled self‐assembly of architectures that display a mesh structure with an average periodic pore size of about 5 to 10 nm. The NH4V4O14 nanobelts are synthesized by using a simple hydrothermal process, and exhibit the same orientation and assemble into bundles, each about 40 to 80 nm in width, 3 to 5 nm in thickness, and up to several millimeters in length. Importantly, the as‐obtained NH4V4O14 nanobelt membranes can highly selectively absorb a variety of organic solvents, covering both polar and non‐polar solvents, for example, the absorbent capacity of glycol is 28 times as high as the initial weight of the membrane, and it can even separate organic solvents with similar polarities and absorb solid contaminants in organic solvents. These highly selective, absorbent membrane materials can be an ideal candidate for the separation and removal of pollution in industrial and environmental applications.
Anion Recognition and Cation‐Induced Molecular Motion in a Heteroditopic [2]Rotaxane
Authors: Leontiev Alexandre V. , Jemmett Charlotte A. , Beer Paul D.
Published: November 2010

A heteroditopic [2]rotaxane consisting of a calix[4]diquinone–isophthalamide macrocycle and 3,5‐bis‐amide pyridinium axle components with the capability of switching between two positional isomers in response to barium cation recognition is synthesised. The anion binding properties of the rotaxane’s interlocked cavity together with Na+, K+, NH4+ and Ba2+ cation recognition capabilities are elucidated by 1H NMR and UV‐visible spectroscopic titration experiments. Upon binding of Ba2+, molecular displacement of the axle’s positively charged pyridinium group from the rotaxane’s macrocyclic cavity occurs, whereas the monovalent cations Na+, K+ and NH4+ are bound without causing significant co‐conformational change. The barium cation induced shuttling motion can be reversed on addition of tetrabutylammonium sulfate.
Selective Multiple Magnesiations of the Thieno[3,2‐b]thiophene Scaffold
Authors: Kunz Thomas , Knochel Paul
Published: November 2010

A full functionalization of all four positions of the thieno[3,2‐b]thiophene scaffold was achieved. Starting from 2,5‐dichlorothieno[3,2‐b]thiophene, magnesiation of the 3‐ and 6‐position using tmpMgCl⋅LiCl furnishes, after trapping with various electrophiles, 3,6‐difunctionalized dichlorothieno[3,2‐b]thiophenes. Subsequent dechlorination and regioselective metalation or regioselective magnesium insertion into the CCl bond provides fully functionalized thieno[3,2‐b]thiophenes. Furthermore, new condensed heterocycles and small oligomers of these compounds with potential applications in material chemistry have been prepared.
Effects of Altered Vitamin and Mineral Nutritional Status on Temperature Regulation and Thermogenesis in the Cold
Authors: Lukaski Henry C. , Smith Scott M.
Published: November 2010

The sections in this article are:

Vitamins

Thiamin

Minerals

Iron

Copper

Zinc

Iodine
Nutrition and Exercise in Adverse Environments
Authors: Buskirk E. R.
Published: November 2010

The sections in this article are:

Dietary Deficiencies

Environmental Heat and Metabolism

Heat Acclimatization/Acclimation

Cold and Caloric Turnover

Cold and Body Fuel

High Terrestrial Altitude

Nutrition in Space
Discovering the unknown: Detection of emerging pathogens using a label‐free light‐scattering system
Authors: Rajwa Bartek , Dundar M. Murat , Akova Ferit , Bettasso Amanda , Patsekin Valery , Dan Hirleman E. , Bhunia Arun K. , Robinson J. Paul
Published: November 2010

A recently introduced technique for pathogen recognition called BARDOT (BActeria Rapid Detection using Optical scattering Technology) belongs to the broad class of optical sensors and relies on forward‐scatter phenotyping (FSP). The specificity of FSP derives from the morphological information that bacterial material encodes on a coherent optical wavefront passing through the colony. The system collects elastically scattered light patterns that, given a constant environment, are unique to each bacterial species and serovar. The notable similarity between FSP technology and spectroscopies is their reliance on statistical machine learning to perform recognition. Currently used methods utilize traditional supervised techniques which assume completeness of training libraries. However, this restrictive assumption is known to be false for most experimental conditions, resulting in unsatisfactory levels of accuracy, poor specificity, and consequently limited overall performance for biodetection and classification tasks. The presented work demonstrates application of the BARDOT system to classify bacteria belonging to the Salmonella class in a nonexhaustive framework, that is, without full knowledge about all the possible classes that can be encountered. Our study uses a Bayesian approach to learning with a nonexhaustive training dataset to allow for the automated detection of unknown bacterial classes. © 2010 International Society for Advancement of Cytometry.
The mirror neuron system and treatment of stroke
Authors: Small Steven L. , Buccino Giovanni , Solodkin Ana
Published: November 2010

Mirror neurons discharge during the execution of ecological goal‐directed manual and oral actions, as well as during the observation of the same actions done by other individuals. These neurons were first identified in the ventral premotor cortex (PMv; area F5) and later on in the inferior parietal lobule (areas PF and PFG) of monkey brain, constituting a “mirror neuron” system. Several pieces of experimental data suggest that a mirror neuron system devoted to hand, mouth, and foot actions might also be present in humans. In the present paper, we review the experimental evidence on the role of the mirror neuron system in action understanding and imitation, both in hand motor function and speech. Based on the features of the mirror neuron system and its role in action understanding and imitation, we discuss the use of action observation and imitation as an approach for systematic training in the rehabilitation of patients with motor impairment of the upper limb and aphasia following stroke. We present the results of some preliminary studies to test this concept, and a discussion of network models as a measure of neurobiological change. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 54:293‐310, 2012.
Age, experience, injury, and the changing brain
Authors: Kolb Bryan , Teskey G. Campbell
Published: November 2010

The fundamental concept in the emerging field of rehabilitation and brain plasticity is that although there is much constancy in brain function and organization across our lifetime, there is remarkable variability as well. This variability reflects the brain's capacity to alter its structure and function in reaction to environmental diversity as well as to perturbations including injury throughout the lifespan. Although the term brain plasticity is now widely used, it is not easily defined and is used to refer to changes at many levels in the nervous system ranging from molecular events, such as changes in gene expression, to behavior (e.g., Shaw & McEachern (Eds.) [2001]. Toward a Theory of Neuroplasticity. Philadelphia, USA: Psychology Press). The focus of our work has been to correlate changes in behavior, neuronal morphology, and the organization of motor maps after cortical injury throughout the lifespan. In this article, we review evidence we have collected from a rat model of normal development and the effects of brain injury, and comment on the general principals that may apply to human stroke and amblyopia. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 54:311‐325, 2012.
Evolution and development of the mammalian dentition: Insights from the marsupial Monodelphis domestica
Authors: Moustakas Jacqueline E. , Smith Kathleen K. , Hlusko Leslea J.
Published: November 2010

To understand developmental mechanisms of evolutionary change, we must first know how different morphologies form. The vast majority of our knowledge on the developmental genetics of tooth formation derives from studies in mice, which have relatively derived mammalian dentitions. The marsupial Monodelphis domestica has a more plesiomorphic heterodont dentition with incisors, canines, premolars, and molars on both the upper and the lower jaws, and a deciduous premolar. The complexity of the M. domestica dentition ranges from simple, unicusped incisors to conical, sharp canines to multicusped molars. We examine the development of the teeth in M. domestica, with a specific focus on the enamel knot, a signaling center in the embryonic tooth that controls shape. We show that the tooth germs of M. domestica express fibroblast growth factor (FGF) genes and Sprouty genes in a manner similar to wild‐type mouse molar germs, but with a few key differences. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.
Caenorhabditis elegans reproductive aging: Regulation and underlying mechanisms
Authors: Luo Shijing , Murphy Coleen T.
Published: November 2010

Female reproductive decline is one of the first aging phenotypes in humans, manifested in increasing rates of infertility, miscarriage, and birth defects in children of mothers over 35. Recently, Caenorhabditis elegans (C. elegans) has been developed as a model to study reproductive aging, and several studies have advanced our knowledge of reproductive aging regulation in this organism. In this review, we describe our current understanding of reproductive cessation in C. elegans, including the relationship between oocyte quality, ovulation rate, progeny number, and reproductive span. We then discuss possible mechanisms of oocyte quality control, and provide an overview of the signaling pathways currently identified to be involved in reproductive span regulation in C. elegans. Finally, we extend the relevance of C. elegans reproductive aging studies to the issue of human female reproductive decline, and we discuss ideas concerning the relationship between reproductive aging and somatic longevity. genesis 49:53–65, 2011. © 2010 Wiley‐Liss, Inc.
Governing the balance between sustainability and competitiveness in urban planning: the case of the Orestad model
Authors: Book Karin , Eskilsson Lena , Khan Jamil
Published: November 2010

Urban development politics are being challenged in various ways today, which becomes obvious when analysing strategies for sustainability versus competitiveness. In parallel to this, alternative ways of financing, planning and organizing urban development and transport projects are becoming more common. However, although the use of publicly owned enterprises in urban development is becoming more common it is still a fairly new phenomenon and differs considerably from development led by a traditional government agency. The question analysed in this article is how well equipped these new governing arrangements are to handle goals of both sustainability and economic competitiveness. As a case study we use a special financial and planning model used in the development of public transport (the metro) and a new urban area (Orestad) in Copenhagen, here called the Orestad model. Special focus is given on the creation of the Orestad Development Corporation, a new hybrid development organization, which was given the mandate to develop both Orestad and the metro. The study shows that there is a lot to gain from both a sustainability and an efficiency perspective by integrating land use development and public transport infrastructure in the same hybrid project organization. While there is definitely a tension between the goals of sustainability and competitive image building, the two do not have to be mutually exclusive. Even though the role of the state is transformed in this new governance arrangement, our case clearly shows how the state remains a crucial actor in sustainability governance. However, there is an obvious risk of a lack of strategic thinking and accountability when a hybrid project‐oriented organization is responsible for planning. Copyright © 2010 John Wiley & Sons, Ltd and ERP Environment.
Sustainability transitions in transition countries: forest policy reforms in South‐eastern Europe
Authors: Weiland Sabine
Published: November 2010

This article deals with forest policy reforms in South‐eastern Europe. It looks at recent developments in the forest sectors in three countries of the region, namely Slovenia, Croatia and Albania. Initial hopes that economic liberalization and democratization of these post‐socialist states would alleviate environmental and sustainability problems have proven too simplistic. Rather, the transition has opened up conflicts around environment and development that begin to show only after the end of the paternalistic and planning‐driven policy approaches of the socialist era. The article analyses the capacities and governance arrangements needed in post‐socialist countries to deal with sustainability issues. Although the major topics in forest policy reforms in transition countries – establishment of provisions for sustainable forest management, privatization of the forest sector, strategies to reconcile sustainable forest management and sustainable economic and human development – are similar, the case studies reveal very different approaches and problems in the transformation of the sector. No blueprint for sustainable governance of forests in transition states exists. Copyright © 2010 John Wiley & Sons, Ltd and ERP Environment.
Fructose‐Based Proline Analogues: Exploring the Prolyl trans/cis‐Amide Rotamer Population in Model Peptides
Authors: Cipolla Laura , Airoldi Cristina , Bini Davide , Gregori Maria , Marcelo Filipa , Jiménez‐Barbero Jesús , Nicotra Francesco
Published: November 2010

A D‐fructose moiety in which a D‐proline ring has been engineered with a spiranic junction in the glycidic scaffold has been used as a proline mimetic. The bicyclic structure, which possesses high structural rigidity, was then included in model peptides to explore their prolyl cis/trans amide rotamer populations. Model peptide conformations were studied by molecular dynamics and NMR experiments.
Expeditious Entry to Enantiopure Mono‐ and Bis(Tricyclic) β‐Lactams by Single or Double [2+2] Cycloaddition of Allenynes
Authors: Alcaide Benito , Almendros Pedro , Aragoncillo Cristina , Gómez‐Campillos Gonzalo
Published: November 2010

A thermal methodology for the expeditious preparation of structurally novel strained tricyclic β‐lactams containing a cyclobutene ring has been developed. Besides, the first examples accounting for the intramolecular double [2+2] cycloaddition of bis(allenyne)s have been achieved through thermolysis of C2‐symmetric or unsymmetric bis(β‐lactam–allenyne)s, which have been prepared by copper‐promoted alkyne homo‐ or cross‐coupling reactions. The bis(tricyclic) ring structures bearing a central seven‐membered ring arise from the regioselective cyclization of the alkyne with the distal bond of the allene, most likely via a radical intermediate.
Comparative response assessment of minimally compliant low‐rise conventional and base‐isolated steel frames
Authors: Erduran Emrah , Dao Nhan D. , Ryan Keri L.
Published: November 2010

In this study, the multi‐intensity seismic response of code‐designed conventional and base‐isolated steel frame buildings is evaluated using nonlinear response history analysis. The results of hazard and structural response analysis for three‐story braced‐frame buildings are presented in this paper. Three‐dimensional models for both buildings are created and seismic response is assessed for three scenario earthquakes. The response history analysis results indicate that the design objectives are met and the performance of the isolated building is superior to the conventional building in the design event. For the Maximum Considered Earthquake, isolation leads to reductions in story drifts and floor accelerations relative to the conventional building. However, the extremely high displacement demands of the isolation system could not be accommodated under normal circumstances, and creative approaches should be developed to control displacements in the MCE. Copyright © 2010 John Wiley & Sons, Ltd.
Aeolian transport rates across raked and unraked beaches on a developed coast
Authors: Nordstrom Karl F. , Jackson Nancy L. , Korotky Katherine H. , Puleo Jack A.
Published: November 2010

Wind characteristics and aeolian transport were measured on a naturally evolving beach and dune and a nearby site where the beach is raked and sand‐trapping fences are deployed. The beaches were composed of moderately well sorted to very well sorted fine to medium sand. The backshore at the raked site was wider and the foredune was more densely vegetated and about 1 m higher than at the unraked site. Wind speeds were monitored using anemometers placed at 1 m elevation and sand transport was monitored using vertical traps during oblique onshore, alongshore and offshore winds occurring in March and April 2009. Inundation of the low backshore through isolated swash channels prevented formation of a continuously decreasing cross‐shore moisture gradient. The surface of the berm crest was dryer than the backshore, making the berm crest the greatest source of offshore losses during offshore winds. The lack of storm wrack on the raked beach reduced the potential for sediment accumulation seaward of the dune crest during onshore winds, and the higher dune crest reduced wind speeds and sediment transport from the dune to the backshore during offshore winds. Accretion at wrack seaward of the dune toe on the unraked beach resulted in a wider dune field and higher, narrower backshore. Although fresh wrack is an effective local trap for aeolian transport, wrack that becomes buried appears to have little effect as a barrier and can supply dry sand for subsequent transport. Aeolian transport rates were greater on the narrower but dryer backshore of the unraked site. Vegetation growth may be necessary to trap sand within zones of buried wrack in order to allow new incipient foredunes to evolve. Copyright © 2010 John Wiley & Sons, Ltd.
The topography of drumlins; assessing their long profile shape
Authors: Spagnolo Matteo , Clark Chris D. , Hughes Anna L.C. , Dunlop Paul
Published: November 2010

The literature on drumlins is pervaded by the notion that their longitudinal profile is usually highly asymmetric with a stoss steeper end and a lee gentler end, and that this can be used to infer the palaeo ice flow direction. The idea is built up in many papers covering more than a century of research. However, most of the early published papers were qualitative in nature and more recent quantitative papers appear to challenge the ubiquity of the classical stoss–lee shape. Here the shape of the drumlin longitudinal profile of 29,238 drumlins in the British Isles has been analysed. Drumlins were grouped into flowsets for which a palaeo ice flow direction was inferred independently of the drumlin shape. Given such ice flow directions it was then possible to identify the upflow and downflow ends of each drumlin and to trace and extract its longitudinal profile. Results indicate that the highest point of the drumlin is usually found around half way along the profile. The mean slope angles at the stoss and lee ends were found to be very similar. Finally, the average profile built from all mapped drumlins appears almost symmetric. In conclusion, drumlin longitudinal profile is far from being the classically asymmetric shape widely reported in text‐book descriptions. Drumlins are mostly symmetrical in shape with a very slight tendency towards the classical shape. Highly asymmetric drumlins do exist but are rare and with an almost equal numbers of drumlins that are the reverse of this. These findings are verified both at the entire population level and the flowset level. This demonstrates that the idealized stoss–lee shape of classically‐asymmetric drumlins is not representative of the population and should be replaced with that of mostly symmetric bumps. Drumlin shape is not a good indicator of the palaeo ice flow direction. Copyright © 2010 John Wiley & Sons, Ltd.
Modeling Hepatitis B Virus X–Induced Hepatocellular Carcinoma in Mice With the Sleeping Beauty Transposon System Δ
Authors: Keng Vincent W. , Tschida Barbara R. , Bell Jason B. , Largaespada David A.
Published: November 2010

The mechanisms associated with hepatitis B virus (HBV)–induced hepatocellular carcinoma (HCC) remain elusive, and there are currently no well-established animal models for studying this disease. Using the Sleeping Beauty transposon as a delivery system, we introduced an oncogenic component of HBV, the hepatitis B virus X (

HBx

) gene, into the livers of fumarylacetoacetate hydrolase (

Fah

) mutant mice via hydrodynamic tail vein injections. Coexpression of

Fah

complementary DNA from the transposon vector allowed for the selective repopulation of genetically corrected hepatocytes in

Fah

mutant mice. The process of hydrodynamic delivery induced liver inflammation, and the subsequent selective repopulation of hepatocytes carrying the transgene(s) could provide useful genetic information about the mechanisms of HBV-induced hyperplasia. Short hairpin RNA directed against transformation-related protein 53 (

shp53

) or other tumor suppressor genes and oncogenes [e.g., constitutively active neuroblastoma RAS viral (v-ras) oncogene homolog with Gly12Val substitution (

NRASG12V

)] could also be codelivered with

HBx

by this system so that we could determine whether oncogenic cooperation existed. We found that the expression of

HBx

induced the activation of β-catenin expression in hydrodynamically injected livers, and this indicated its association with the

Wnt

signaling pathway in HBV-induced hyperplasia.

HBx

coinjected with

shp53

accelerated the formation of liver hyperplasia in these mice. As expected, constitutively active

NRASG12V

alone was sufficient to induce liver hyperplasia, and its tumorigenicity was augmented when it was coinjected with

shp53
. Interestingly,

HBx

did not seem to cooperate with constitutively active

NRASG12V

in driving liver tumorigenesis.

Conclusion:

This system can be used as a model for studying the various genetic contributions of HBV to liver hyperplasia and finally HCC in an

in vivo

system. (Hepatology 2010;.)
A candidate CpG SNP approach identifies a breast cancer associated ESR1‐SNP
Authors: Harlid Sophia , Ivarsson Malin I.L. , Butt Salma , Hussain Shehnaz , Grzybowska Ewa , Eyfjörd Jorunn Erla , Lenner Per , Försti Asta , Hemminki Kari , Manjer Jonas , Dillner Joakim , Carlson Joyce
Published: November 2010

Altered DNA methylation is often seen in malignant cells, potentially contributing to carcinogenesis by suppressing gene expression. We hypothesized that heritable methylation potential might be a risk factor for breast cancer and evaluated possible association with breast cancer for single nucleotide polymorphisms (SNPs) either involving CpG sequences in extended 5′‐regulatory regions of candidate genes (ESR1, ESR2, PGR, and SHBG) or CpG and missense coding SNPs in genes involved in methylation (MBD1, MECP2, DNMT1, MGMT, MTHFR, MTR, MTRR, MTHFD1, MTHFD2, BHMT, DCTD, and SLC19A1). Genome‐wide searches for genetic risk factors for breast cancers have in general not investigated these SNPs, because of low minor allele frequency or weak haplotype associations. Genotyping was performed using Mass spectrometry‐Maldi‐Tof in a screening panel of 538 cases and 1,067 controls. Potential association to breast cancer was identified for 15 SNPs and one of these SNPs (rs7766585 in ESR1) was found to associate strongly with breast cancer, OR 1.30 (95% CI 1.17–1.45; p‐value 2.1 × 10−6), when tested in a verification panel consisting of 3,211 unique breast cancer cases and 4,223 unique controls from five European biobank cohorts. In conclusion, a candidate gene search strategy focusing on methylation‐related SNPs did identify a SNP that associated with breast cancer at high significance.
Elevated frequencies of CD4+CD25+CD127lo regulatory T cells is associated to poor prognosis in patients with acute myeloid leukemia
Authors: Shenghui Zhang , Yixiang Han , Jianbo Wu , Kang Yu , Laixi Bi , Yan Zhuang , Xi Xu
Published: November 2010

Regulatory T cells (Treg) mediate amelioration of disease and immune homeostasis by inhibiting immune activation and maintaining peripheral immune tolerance. The suppressive mechanisms and clinical significance of Treg have not been completely elucidated in patients with acute myeloid leukemia (AML). Here, we demonstrated that CD127 in combination with CD4 and CD25 can identify FoxP3+ Treg in peripheral blood (PB) and bone marrow (BM) using multicolor flow cytometry. We showed that the CD4+CD25+CD127lo Treg frequencies were significantly increased and their phenotypes were different in PB from newly diagnosed AML patients compared to those from healthy volunteers (HVs). Moreover, the Treg frequencies were significantly higher in BM than those from PB in the same patients. The Treg frequencies were reduced when patients achieved complete remission (CR) and were increased when patients relapsed. The Treg frequencies at diagnosis in PB and BM of patients who had achieved CR were lower than those of patients who had persistent leukemia or died, respectively. CD4+CD25+ Treg were isolated by magnetic‐activated cell sorting and tested for suppressive functions in coculture with allogeneic carboxyfluorescein diacetate succinimidylester‐labeled CD4+CD25− responder cells. Suppression mediated by Treg was higher in AML patients compared to HVs. No significant differences were observed in the cytokines production of Treg, including interferon‐gamma (IFN‐γ), interleukin (IL)‐4,IL‐2 and IL‐10, between patients with AML and HVs. Our study suggests that Treg may play a role in the pathogenesis of AML, and sequential measurements of Treg frequency may have clinical value in the evaluation of therapeutic effects and clinical outcome.
T cells reactive with HLA‐A*0201 peptides from the histone demethylase JARID1B are found in the circulation of breast cancer patients
Authors: Coleman Julia A. , Correa Isabel , Cooper Lucienne , Bohnenkamp Hermann R. , Poulsom Richard , Burchell Joy M. , Taylor‐Papadimitriou Joyce
Published: November 2010

The nuclear protein PLU‐1/JARID1B/KDM5 is widely expressed in breast cancers while showing highly restricted expression in normal adult tissues. To investigate whether JARID1B is a potential target antigen for immunotherapy of breast cancer, we have analyzed the responses of CD8+ T cells to JARID1B HLA‐A*0201 peptides in vitro and used peptide multimers to detect the presence of JARID1B reactive T cells in the circulation of breast cancer patients. Peptides were selected using two web‐based algorithms: criteria for inclusion being a high score in both prediction algorithms, and nonhomology with retinoblastoma binding protein‐2 (RBP2/JARID1A/KDM5A). A 65‐peptide panel was selected and assayed for binding strength by competition assay to obtain the IC50. The immunogenicity in vitro of these peptides was assessed by T cell stimulation experiments, using autologous dendritic cells as APCs in the first rounds followed by autologous lymphoblasts. Fourteen of the peptides assayed produced cultures having >2% of the CD8+ cells being IFN‐γ+ after 3–6 rounds of stimulation. An HLA‐A*0201 cell line could activate the specific T cells if pulsed with peptide, but endogenous peptide levels were insufficient for activation. Nevertheless, multimer staining of circulating T cells from breast cancer patients showed a significantly higher percentage of multimer positive CD8+ T cells, as compared to healthy adults for two of three JARID1B epitopes tested. One of these, peptide 73 (QLYALPCVL), was analyzed for memory phenotype, and found to have a significantly higher proportion of central memory T cells than the control group, demonstrating a previous exposure to the peptide.
WAVE3, an actin remodeling protein, is regulated by the metastasis suppressor microRNA, miR‐31, during the invasion‐metastasis cascade
Authors: Sossey‐Alaoui Khalid , Downs‐Kelly Erinn , Das Mitali , Izem Lahoucine , Tubbs Raymond , Plow Edward F.
Published: November 2010

WAVE3, an actin cytoskeleton remodeling protein, is highly expressed in advanced stages of breast cancer and influences tumor cell invasion. Loss of miR‐31 has been associated with cancer progression and metastasis. Here, we show that the activity of WAVE3 to promote cancer cell invasion is regulated by miR‐31. An inverse correlation was demonstrated between expression levels of WAVE3 and miR‐31 in invasive versus noninvasive breast cancer cell lines. miR‐31 directly targeted the 3'‐UTR of the WAVE3 mRNA and inhibited its expression in the invasive cancer cells, i.e., miR‐31‐mediated down‐regulation of WAVE3 resulted in a significant reduction in the invasive phenotype of cancer cells. This relationship was specific to the loss of WAVE3 expression because re‐expression of a miR‐31‐resistant form of WAVE3 reversed miR‐31‐mediated inhibition of cancer cell invasion. Furthermore, expression of miR‐31 correlates inversely with breast cancer progression in humans, where an increase in expression of miR‐31 target genes was observed as the tumors progressed to more aggressive forms. In conclusion, a novel mechanism for the regulation of WAVE3 expression in cancer cells has been identified, which controls the invasive properties of cancer cells. The study also identifies a critical role for WAVE3, downstream of miR‐31, in the invasion‐metastasis cascade.
A pooled analysis of 14 cohort studies of anthropometric factors and pancreatic cancer risk
Authors: Genkinger Jeanine M. , Spiegelman Donna , Anderson Kristin E. , Bernstein Leslie , van den Brandt Piet A. , Calle Eugenia E. , English Dallas R. , Folsom Aaron R. , Freudenheim Jo L. , Fuchs Charles S. , Giles Graham G. , Giovannucci Edward , Horn‐Ross Pamela L. , Larsson Susanna C. , Leitzmann Michael , Männistö Satu , Marshall James R. , Miller Anthony B. , Patel Alpa V. , Rohan Thomas E. , Stolzenberg‐Solomon Rachael Z. , Verhage Bas AJ , Virtamo Jarmo , Willcox Bradley J. , Wolk Alicja , Ziegler Regina G. , Smith‐Warner Stephanie A.
Published: November 2010

Epidemiologic studies of pancreatic cancer risk have reported null or nonsignificant positive associations for obesity, while associations for height have been null. Waist and hip circumference have been evaluated infrequently. A pooled analysis of 14 cohort studies on 846,340 individuals was conducted; 2,135 individuals were diagnosed with pancreatic cancer during follow‐up. Study‐specific relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Compared to individuals with a body mass index (BMI) at baseline between 21–22.9 kg/m2, pancreatic cancer risk was 47% higher (95%CI:23–75%) among obese (BMI ≥ 30 kg/m2) individuals. A positive association was observed for BMI in early adulthood (pooled multivariate [MV]RR = 1.30, 95%CI = 1.09–1.56 comparing BMI ≥ 25 kg/m2 to a BMI between 21 and 22.9 kg/m2). Compared to individuals who were not overweight in early adulthood (BMI < 25 kg/m2) and not obese at baseline (BMI < 30 kg/m2), pancreatic cancer risk was 54% higher (95%CI = 24–93%) for those who were overweight in early adulthood and obese at baseline. We observed a 40% higher risk among individuals who had gained BMI ≥ 10 kg/m2 between BMI at baseline and younger ages compared to individuals whose BMI remained stable. Results were either similar or slightly stronger among never smokers. A positive association was observed between waist to hip ratio (WHR) and pancreatic cancer risk (pooled MVRR = 1.35 comparing the highest versus lowest quartile, 95%CI = 1.03–1.78). BMI and WHR were positively associated with pancreatic cancer risk. Maintaining normal body weight may offer a feasible approach to reducing morbidity and mortality from pancreatic cancer.
Podoplanin expression correlates with sentinel lymph node metastasis in early squamous cell carcinomas of the oral cavity and oropharynx
Authors: Huber Gerhard Frank , Fritzsche Florian R. , Züllig Lena , Storz Martina , Graf Nicole , Haerle Stephan K. , Jochum Wolfram , Stoeckli Sandro J. , Moch Holger
Published: November 2010

In patients with early head and neck squamous cell carcinoma (HNSCC), occult lymph node metastasis is difficult to predict by clinical or pathological parameters. However, such parameters are necessary to select patients either for elective neck dissection or the sentinel lymph node (SLN) procedure. The membrane glycoprotein podoplanin is normally expressed in lymphatic endothelial cells. Recently, expression of podoplanin by cancer cells was demonstrated to promote tumor cell motility and tumor lymphangiogenesisin vitro. The value of cancer cell‐expressed podoplanin was to be determined as a predictive marker for SLN metastasis in early HNSCC of the oral cavity and oropharynx. One hundred twenty patients with HNSCC of the oral cavity and oropharynx undergoing a SLN biopsy were enrolled in this prospective clinical trial of SLN biopsy. Cancer cell‐expressed podoplanin was determined by immunohistochemistry using tissue microarrays. Podoplanin expression was quantified by the intensity reactivity score and categorized into expression and nonexpression. SLN examination revealed occult metastasis in 45 patients (37.5%). Twenty‐nine of 120 (24.2%) primary HNSCC showed podoplanin expression. Podoplanin expression correlated significantly with SLN metastasis (p= 0.029) and remained a significant predictor for lymph node status even after controlling for tumor stage (p= 0.028). As a predictive marker for SLN metastasis, however, podoplanin expression reached a sensitivity of a mere 36% and a specificity of 83%. Podoplanin expression is associated with metastasis to lymph nodesin vivo.Podoplanin immunohistochemistry in early HNSCC of the oral cavity and oropharynx may help to select patients for the SLN procedure and to identify patients with increased risk for presence of occult lymph node metastasis in the neck.
Protective effects of lemongrass (Cymbopogon citratusSTAPF) essential oil on DNA damage and carcinogenesis in female Balb/C mice
Authors: Bidinotto Lucas T. , Costa Celso A. R. A. , Salvadori Daisy M. F. , Costa Mirtes , Rodrigues Maria A. M. , Barbisan Luís F.
Published: November 2010

This study investigated the protective effect of oral treatment with lemongrass (Cymbopogon citratusSTAPF) essential oil (LGEO) on leukocyte DNA damage induced byN‐methyl‐N‐nitrosurea (MNU). Also, the anticarcinogenic activity of LGEO was investigated in a multi‐organ carcinogenesis bioassay induced by 7,12‐dimethylbenz(a)antracene, 1,2‐dimethylhydrazine andN‐butyl‐N‐(4‐hydroxibuthyl)nitrosamine in Balb/C female Balb/c mice (DDB‐initiated mice). In the short‐term study, the animals were allocated into three groups: vehicle group (negative control), MNU group (positive control) and LGEO 500 mg kg−1(five times per week for 5 weeks) plus MNU group (test group). Blood samples were collected to analyze leukocyte DNA damage by comet assay 4 h after each MNU application at the end of weeks 3 and 5. The LGEO 500 mg kg−1treated group showed significantly lower (P< 0.01) leukocyte DNA damage than its respective positive group exposed to MNU alone at week 3. In the medium‐term study, DDB‐initiated mice were allocated into three groups: vehicle group (positive control) and LGEO 125 or 500 mg kg−1(five times per week for 6 weeks; test groups). At week 20, all animals were euthanized and mammary glands, colon and urinary bladder were processed for histopathological analyses for detection of preneoplastic and neoplastic lesions. A slight non‐significant effect of treatment with LGEO 500 mg kg−1in reducing development of alveolar and ductal mammary hyperplasia was found (P= 0.075). Our findings indicate that lemongrass essential oil provided protective action against MNU‐induced DNA damage and a potential anticarcinogenic activity against mammary carcinogenesis in DDB‐initiated female Balb/C mice. Copyright © 2010 John Wiley & Sons, Ltd.
APPswe/Aβ regulation of osteoclast activation and RAGE expression in an age-dependent manner
Authors: Cui Shun , Xiong Fei , Hong Yan , Jung Ji-Ung , Li Xing-Sheng , Liu Jian-Zhong , Yan Riqiang , Mei Lin , Feng Xu , Xiong Wen-Cheng
Published: November 2010

Alzheimer's disease (AD), one of the most dreaded neurodegenerative disorders, is characterized by cortical and cerebrovascular amyloid β peptide (Aβ) deposits, neurofibrillary tangles, chronic inflammation, and neuronal loss. Increased bone fracture rates and reduced bone density are commonly observed in patients with AD, suggesting one or more common denominators between both disorders. However, very few studies are available that have addressed this issue. Here, we present evidence for a function of amyloid precursor protein (APP) and Aβ in regulating osteoclast (OC) differentiation in vitro and in vivo. Tg2576 mice, which express the Swedish mutation of APP (APPswe) under the control of a prion promoter,1,2 exhibit biphasic effects on OC activation, with an increase of OCs in younger mice (< 4 months old), but a decrease in older Tg2576 mice (> 4 months old). The increase of OCs in young Tg2576 mice appears to be mediated by Aβ oligomers and receptor for advanced glycation end products (RAGE) expression in bone marrow macrophages (BMMs). However, the decrease of OC formation and activity in older Tg2576 mice may be due to the increase of soluble rage (sRAGE) in aged Tg2576 mice, an inhibitor of RANKL-induced osteoclastogenesis. These results suggest an unexpected function of APPswe/Aβ, reveal a mechanism underlying altered bone remodeling in AD patients, and implicate APP/Aβ and RAGE as common denominators for both AD and osteoporosis. © 2011 American Society for Bone and Mineral Research.
Resistance/Reactance Level
Authors: Beutler Larry E. , Harwood T. Mark , Michelson Aaron , Song Xiaoxia , Holman John
Published: November 2010

Psychotherapists from all professions and perspectives periodically struggle to effectively manage a patient's resistance to change. This article provides definitions and examples of patient‐treatment matching applied to patient resistance or reactance. We report the results from an original meta‐analysis of 12 select studies (N = 1,102) on matching therapist directiveness to patient reactance. Our findings support the hypothesis that patients exhibiting low levels of trait‐like resistance respond better to directive types of treatment, while patients with high levels of resistance respond best to nondirective treatments (d = .82). Limitations of the research reviewed are noted, and practice recommendations are advanced. © 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 67:133–142, 2011.
What works for whom: Tailoring psychotherapy to the person
Authors: Norcross John C. , Wampold Bruce E.
Published: November 2010

This article introduces the issue of the Journal of Clinical Psychology: In Session devoted to evidence‐based means of adapting psychotherapy to the patient's (transdiagnostic) characteristics. Practitioners have long realized that treatment should be tailored to the individuality of the patient and the singularity of his or her context, but only recently has sufficient empirical research emerged to reliably guide practice. This article reviews the work of an interdivisional task force and its dual aims of identifying elements of effective therapy relationships (what works in general) and identifying effective methods of adapting treatment to the individual patient (what works in particular). The task force judged four patient characteristics (reactance/resistance, preferences, culture, religion/spirituality) to be demonstrably effective in adapting psychotherapy and another two (stages of change, coping style) as probably effective. Two more patient facets (expectations, attachment style) were related to psychotherapy outcome but possessed insufficient research as a means of adaptation. This special issue provides research‐supported methods of individualizing psychotherapy to the person, in addition to his or her diagnosis. © 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 67:127–132, 2011.
Ontogeny of ENaC expression in the gills and the kidneys of the Japanese black salamander (Hynobius nigrescens Stejneger)
Authors: Uchiyama Minoru , Kumano Tomoko , Konno Norifumi , Yoshizawa Hideki , Matsuda Kouhei
Published: November 2010

A full‐length cDNA cloning and tissue distribution of epithelial sodium channel (ENaC) protein were studied during ontogeny by immunohistochemistry in the external gills, and the kidney, pronephros and mesonephros, of the Japanese black salamander, Hynobius nigrescens (Family Hynobiidae; a primitive caudate species). The amino acid sequence of Hynobius ENaCα is 64 and 63% identical to Bufo ENaCα and Rat ENaCα, respectively. In aquatic larva salamander at the digit differentiation stage, Hynobius ENaCα mRNA was expressed in the external gills and pronephros. In the adult, the mRNA was expressed in the skin and the mesonephros. In the larvae, juvenile, and adult specimens, Hynobius ENaCα immunoreactivity was observed at the apical cell membrane of the external gills, late parts of the distal tubules, and mesonephric duct in the kidney. Colocalization of the apical Hynobius ENaCα and the basolateral Na+,K+‐ATPase was observed in the tubular cells of pronephros and mesonephros. These results suggest that Hynobius ENaCα plays an important role in the regulation of sodium transport in the external gills and pronephros of aquatic larvae, and in the skin and mesonephros of terrestrial adult. This is the first study to indicate ENaC expression during ontogeny in amphibians. Since no orthologs or paralogs for ENaC have been found, so far, in databases of the genomes of teleosts, it is assumed that ENaC might have played a role in terrestriality during the evolution of early tetrapods, the origin of lissamphibians. J. Exp. Zool. (Mol. Dev. Evol.) 316:135–145, 2011. © 2010 Wiley‐Liss, Inc.