bluuebunny/crossref_metadata_2025_split huggingface dataset:
Climate and landscape drivers of tree decline in a Mediterranean ecoregion
Authors: Brouwers Niels C. , Mercer Jack , Lyons Tom , Poot Pieter , Veneklaas Erik , Hardy Giles 
Published: December 2012

AbstractClimate change and anthropogenic land use are increasingly affecting the resilience of natural ecosystems. In Mediterranean ecoregions, forests and woodlands have shown progressive declines in health. This study focuses on the decline of an endemic woodland tree species,Eucalyptus wandoo(wandoo), occurring in the biodiversity hotspot of southwest Western Australia. We determined the change in health of wandoo stands between 2002 and 2008 across its geographic and climatic range, and associated this change in health with non‐biotic variables focusing on: (1) fragment metrics; (2) topography; (3) soil characteristics; and (4) climate. Only fragment metrics and climate variables were found to be significantly related to the observed change in health. Stands that were small with high perimeter/area ratios were found to be most sensitive to health declines. Recent increases in autumn temperatures and decreases in annual rainfall were negatively affecting health of wandoo most prominently in the low rainfall zone of its climatic range. Together, these results suggest the onset of range contraction for this ecologically important species, which is likely to be exacerbated by projected future changes in climate. Our results emphasize the importance of establishing monitoring programs to identify changes in health and decline trends early to inform management strategies, particularly in the sensitive Mediterranean ecoregions.
The Glaser–Hay Reaction: Optimization and Scope Based on 13C NMR Kinetics Experiments
Authors: Vilhelmsen Mie H. , Jensen Jonas , Tortzen Christian G. , Nielsen Mogens B. 
Published: December 2012

AbstractThe oxidative Glaser–Hay coupling of two terminal alkynes to furnish a butadiyne is a key reaction for acetylenic scaffolding. Although the reaction is performed under rather simple conditions [CuCl/TMEDA/O2 (air)], the mechanism is still under debate. Herein we present detailed studies on the scope of this reaction by using both 13C NMR and UV/Vis spectroscopic methods. The former method was used to study the kinetics of the coupling of aryl‐substituted alkynes as the aryl carbon resonances of the reactants and products have similar NOEs and relaxation times. The reaction was found to be zero‐order with respect to the terminal alkyne reactant under standard preparative conditions. Moreover, as the reaction proceeded, a clear change to slower reaction kinetics was observed, but it was still apparently zero‐order. The onset of this change was found to depend on the catalyst loading. This unfavorable change in reaction profile could be avoided by adding molecular sieves to the reaction mixture, thereby removing the water that is accumulated from the air and produced in the reaction in which dioxygen acts as the oxidizing agent. Not unexpectedly, the stirring rate, and hence uptake of air (O2), was found to have a significant effect on the rate of the reaction: The percentage of alkyne remaining after a certain time decreased linearly with the rate of stirring. On the basis of systematic studies, the optimized conditions for the coupling reaction using CuCl/TMEDA as the catalyst system are presented. Finally, we investigated the effect of different ligands and found that piperidine can also be conveniently employed as a ligand, albeit monodentate, in accord with related studies.
4‐Alkenyl‐2‐aminothiazoles: Smart Dienes for Polar [4 + 2] Cycloadditions
Authors: Alajarin Mateo , Cabrera Jose , Sanchez‐Andrada Pilar , Orenes Raul‐Angel , Pastor Aurelia 
Published: December 2012

AbstractAn exhaustive investigation into the [4 + 2] cycloadditions of 4‐alkenyl‐2‐aminothiazoles with a wide range of dienophiles has been carried out. 4‐Alkenyl‐2‐aminothiazoles act as good in‐out dienes, reacting with dienophiles bearing electron‐withdrawing groups. The heteroannulations, typically conducted under mild conditions, were endo‐selective when cyclic dienophiles were used, and regioselective when the reactions are conducted with unsymmetrical dienophiles. The endo‐selective processes presumably take place by concerted but highly asynchronous mechanisms. In contrast, the low levels of endo selectivity and the lack of stereospecificity in the reactions with certain acyclic dienophiles indicate a stepwise mechanism with a zwitterion as the most plausible intermediate. The course of the reaction changes when the highly reactive PTAD and TCNE are used as dienophiles, since in these cases, only addition products were obtained. Calculations of the HOMO and LUMO energy values of representative 4‐alkenyl‐2‐aminothiazoles, and the results of π‐facial diastereoselective processes by using chiral substrates are also disclosed.
Synthetic Progress in cMyc‐Max Oncoprotein Miniaturization: Semi‐Online Monitoring Gives Solid‐Phase Access to Hydrophobic b(‐HLH‐)ZIP Peptidosteroid Tweezers
Authors: Verzele Dieter , Madder Annemieke 
Published: December 2012

AbstractMiniature versions of basic leucine zipper (bZIP) and basic helix–loop–helix zipper (b‐HLH‐ZIP) transcription factors are promising tools for molecular dissection of the genetic information in a post‐genomic context. Despite the opportunities of genome interfering agents based on certain oncogenic zipper proteins, structural mimicry of transcription factors is a delicate undertaking, and experimental fine‐tuning through bottom‐up organic chemistry could benefit from solid‐phase/library approaches. Involved in a variety of human pathologies, we became interested in the miniaturization of the cMyc‐Max b‐HLH‐ZIP oncoprotein, and herein elaborate on our synthetic progress in that direction. A bile acid scaffold was successfully employed as artificial dimerization interface in this new type of transcription factor model. Orthogonality of the applied Alloc/Boc/Fmoc chemistries allowed the synthesis of both homo‐ and heterodimeric peptidosteroid conjugates, covalently restricted with defined geometrical properties. Recognition peptides were assembled through standard Fmoc/tBu solid‐phase peptide synthesis (SPPS) chemistry, assisted by automated procedures for consecutive chain elongation on solid support. Invaluable to monitor present strategy, a photocleavable linker allowed rapid, yet detailed analysis of side chain protected peptide intermediates, liberated from the sampled resin, by reverse‐phase HPLC and MALDI‐TOF‐MS. By decorating each scaffold position with two basic region peptides in a 2 × 2 design, a first generation of unprecedented b(‐HLH‐)ZIP peptidosteroids was efficiently obtained. As such, a versatile methodology amenable to library generation is presented.
Synthesis of Functionalized, Sterically Congested Calix[4]phyrin Macrocycles Using Donor–Acceptor‐Substituted Cyclopropanes – First Example of a Mono‐meso‐spirolactone Incorporated into a Calix[4]phyrin
Authors: Beyzavi M. Hassan , Lentz Dieter , Reissig Hans‐Ulrich , Wiehe Arno 
Published: December 2012

AbstractCalix[4]phyrins are an important class of hybrid macrocyclic systems at the interface between porphyrins and calixpyrroles (porphyrinogens). A new stepwise synthesis of oxidation‐resistant meso‐hydrogenated calix[4]phyrins is reported, which allows variable substitution in the residues of their sp2‐meso‐centers without the need for a porphyrin intermediate. It relies on the acid‐catalyzed condensation of a sterically hindered donor–acceptor‐substituted cyclopropane precursor with pyrrole to form a sterically congested dipyrromethane. This was subsequently condensed with a wide range of alkyl and aryl aldehydes bearing electron‐donating or electron‐withdrawing substituents followed by an oxidation step to form stable calix[4]phyrin(1.1.1.1)s with bridging meso‐CH hydrogen atoms through an acid‐promoted dehydrative condensation. The methodology avoids any need for premetallation of the macrocycle and/or the use of organometallic catalysts or reagents and allows the incorporation of the bulky cyclopropane‐derived substituents specifically into the 5,15‐meso‐like positions. The resulting regioisomerically pure products display conformational features that reflect their mixed nature between porphyrins and calixpyrroles and they were assessed by X‐ray diffraction analysis, NMR techniques and UV/Vis spectroscopy. The possibility to introduce key functional groups enables subsequent modification of these calix[4]phyrins and allows their connection to other groups such as biologically active moieties. Of special interest is an unprecedented example of an acid‐driven lactonization that results in the incorporation of a mono‐meso‐spirolactone into a calix[4]phyrin(1.1.1.1). Moreover, it is demonstrated that this approach to calix[4]phyrins is also applicable to other sterically congested dipyrromethanes.
A novel anonymous authentication scheme without cryptography
Authors: Shi Run‐hua , Zhong Hong , Huang Liu‐sheng 
Published: December 2012

ABSTRACTIn this paper, we present a novel anonymous authentication scheme without employing any symmetric or asymmetric cryptosystem. The security of our scheme is guaranteed by the basic theories for solving linear equations, which can ensure it is unconditionally secure. The proposed scheme is adaptable for resource‐constrained devices or wireless networks well, because it only needs to perform several scalar multiplications instead of complex cryptographic operations and takes only one round of message exchange (challenge–response) between the verification centre and the legal user. Copyright © 2012 John Wiley & Sons, Ltd.
Antitumor effects of combining metronomic chemotherapy with the antivascular action of ultrasound stimulated microbubbles
Authors: Todorova Margarita , Agache Vlad , Mortazavi Omid , Chen Branson , Karshafian Raffi , Hynynen Kullervo , Man Shan , Kerbel Robert S. , Goertz David E. 
Published: December 2012

AbstractConsiderable effort is being directed toward investigating the use of ultrasound (US) stimulated microbubbles (MB) to promote the uptake of anticancer agents in tumors. In this study we propose and investigate a new method for combining therapeutic ultrasound with anticancer agents, which is to induce antivascular effects and combine these with an antiangiogenic treatment strategy, in this case metronomic chemotherapy. This is effectively a vascular targeting rather than a drug delivery approach. Experiments were conducted on MDA‐MB‐231 breast cancer tumors implanted in athymic mice. Metronomic cyclophosphamide (MCTX) was employed as an antiangiogenic therapy and was administered through the drinking water. Ultrasound stimulated microbubble treatments (USMB) were conducted at 1 MHz employing short bursts (0.00024 duty cycle) at 1.6 MPa in combination with the commercial microbubble agent Definity. USMB treatments were performed on a weekly basis for 4 weeks and MCTX was administered for 10 weeks. The USMB induced an acute reduction of blood flow as confirmed with US contrast imaging and DiOC7 perfusion staining. Longitudinal experiments demonstrated that significant growth inhibition occurred in MCTX‐only and USMB‐only treatment groups relative to control tumors. The combined USMB and MCTX treatment group showed significant growth inhibition and survival prolongation relative to the USMB‐only (p < 0.01) and MCTX‐only treatment groups (p < 0.01). These results indicate the feasibility of a new approach to combining therapeutic ultrasound with an anticancer agent.
Meta‐analysis of microRNA expression in lung cancer
Authors: Võsa Urmo , Vooder Tõnu , Kolde Raivo , Vilo Jaak , Metspalu Andres , Annilo Tarmo 
Published: December 2012

AbstractThe prognostic and diagnostic value of microRNA (miRNA) expression aberrations in lung cancer has been studied intensely in recent years. However, due to the application of different technological platforms and small sample size, the miRNA expression profiling efforts have led to inconsistent results between the studies. We performed a comprehensive meta‐analysis of 20 published miRNA expression studies in lung cancer, including a total of 598 tumor and 528 non‐cancerous control samples. Using a recently published robust rank aggregation method, we identified a statistically significant miRNA meta‐signature of seven upregulated (miR‐21, miR‐210, miR‐182, miR‐31, miR‐200b, miR‐205 and miR‐183) and eight downregulated (miR‐126‐3p, miR‐30a, miR‐30d, miR‐486‐5p, miR‐451a, miR‐126‐5p, miR‐143 and miR‐145) miRNAs. We conducted a gene set enrichment analysis to identify pathways that are most strongly affected by altered expression of these miRNAs. We found that meta‐signature miRNAs cooperatively target functionally related and biologically relevant genes in signaling and developmental pathways. We have shown that such meta‐analysis approach is suitable and effective solution for identification of statistically significant miRNA meta‐signature by combining several miRNA expression studies. This method allows the analysis of data produced by different technological platforms that cannot be otherwise directly compared or in the case when raw data are unavailable.
Knockdown of prolyl‐4‐hydroxylase domain 2 inhibits tumor growth of human breast cancer MDA‐MB‐231 cells by affecting TGF‐β1 processing
Authors: Wottawa Marieke , Leisering Pia , Ahlen Melanie von , Schnelle Moritz , Vogel Sabine , Malz Cordula , Bordoli Mattia Renato , Camenisch Gieri , Hesse Amke , Napp Joanna , Alves Frauke , Kristiansen Glen , Farhat Katja , Katschinski Dörthe Magdalena 
Published: December 2012

AbstractThe prolyl‐4‐hydroxylase domain 1–3 (PHD1–3) enzymes are regulating the protein stability of the α‐subunit of the hypoxia‐inducible factor‐1 (HIF‐1), which mediates oxygen‐dependent gene expression. PHD2 is the main isoform regulating HIF‐1α hydroxylation and thus stability in normoxia. In human cancers, HIF‐1α is overexpressed as a result of intratumoral hypoxia which in turn promotes tumor progression. The role of PHD2 for tumor progression is in contrast far from being thoroughly understood. Therefore, we established PHD2 knockdown clones of MDA‐MB‐231 breast cancer cells and analyzed their tumor‐forming potential in a SCID mouse model. Tumor progression was significantly impaired in the PHD2 knockdown MDA‐MB‐231 cells, which could be partially rescued by re‐establishing PHD2 expression. In a RNA profile screen, we identified the secreted phosphoprotein 1 (SPP1) as one target, which is differentially regulated as a consequence of the PHD2 knockdown. Knockdown of PHD2 drastically reduced the SPP1 expression in MDA‐MB‐231 cells. A correlation of SPP1 and PHD2 expression was additionally verified in 294 invasive breast cancer biopsies. In subsequent analyses, we identified that PHD2 alters the processing of transforming growth factor (TGF)‐β1, which is highly involved in SPP1 expression. The altered processing capacity was associated with a dislocation of the pro‐protein convertase furin. Thus, our data demonstrate that in MDA‐MB‐231 cells PHD2 might affect tumor‐relevant TGF‐β1 target gene expression by altering the TGF‐β1 processing capacity.
Productivity increment of biodegradable and biorenewable copolymer containing 3‐hydroxyvalerate monomer initiated by alcohols as precursor substrates
Authors: Shantini K. , Bhubalan Kesaven , Yahya Ahmad Ramli Mohd , Amirul A.A. 
Published: December 2012

AbstractBackgroundThe production cost and the material properties of polyhydroxyalkanoate (PHA), a biodegradable plastic are common issues of debate. It has become a constant challenge for researchers to find suitable and relatively cheap carbon substrates. This study has investigated the production of poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) [P(3HB‐co‐3HV)], using a combination of fatty acids and alcohols. The fermentation process described in this study also highlights the potential use of 1‐pentanol for the generation of 3HV monomer, in contrast to odd carbon numbered volatile fatty acids, which are known to exert some levels of toxicity towards the cells.ResultsAmong the various mixtures of fatty acids and 3HV precursors, the mixture of 0.50 wt% C oleic acid and 0.06 wt% C 1‐pentanol was found suitable for the production of this copolymer. It was found that Cupriavidus sp. USMAA2‐4 could produce up to 56 wt% of P(3HB‐co‐3HV) with 8 mol% 3HV monomer units. The 3HV monomer composition was also successfully regulated in the range 3–66 mol% by manipulating the culture conditions. The number average molecular weight of the copolymer produced was in the range 217–351 kDa.ConclusionThe findings of this study might be used as a platform for scale‐up production of 3HV copolymers with different monomer compositions using mixtures of oleic acid and alcohols, namely 1‐pentanol for a sustainable production process.© 2012 Society of Chemical Industry
The structural and biochemical basis for cellulose biodegradation
Authors: Wang Mingyu , Liu Kai , Dai Li , Zhang Jie , Fang Xu 
Published: December 2012

AbstractThe increasing petroleum price and the foreseeable depletion of fossil fuels has prompted research on bioenergy, particularly bioethanol and biobutanol from renewable lignocellulosic biomass, the primary component of which is cellulose. One key requirement of lignocellulose degradation is to improve the efficiency of a group of enzymes with general name cellulase, the collaboration of which degrades cellulose to glucose. Significant progress has been made in the last decade on understanding the structural and chemical properties of the substrate cellulose, the structural and biochemical properties of cellulases, their enzymatic mechanisms and the mechanism of synergistic catalysis by cellulases. This manuscript reviews the progress in the aforementioned fields, particularly the structural basis and enzymatic mechanisms of reactions leading to the degradation of cellulose. Based on these discoveries, popular models of enzymatic cellulose degradation are discussed, in the hope of benefiting further in‐depth investigations of this complex, multi‐component enzymatic reaction.© 2012 Society of Chemical Industry
Development of an AdEasy‐based system to produce first‐ and second‐generation adenoviral vectors with tropism for CAR‐ or CD46‐positive cells
Authors: Janssen Josephine M. , Liu Jin , Skokan Jaroslav , Gonçalves Manuel A. F. V. , de Vries Antoine A. F. 
Published: December 2012

AbstractBackgroundThe AdEasy system has acquired preeminence amongst the various methods for producing first‐generation, early region 1 (E1)‐deleted human adenovirus (HAdV) vectors (AdVs) as a result of the fast and reproducible recovery of full‐length AdV genomes via homologous recombination in Escherichia coli.MethodsFrom the classical AdEasy system, a new production platform was derived to assemble first‐ and second‐generation [i.e. E1‐ plus early region 2A (E2A)‐deleted] AdVs displaying on their surface HAdV serotype 5 (HAdV5) fibers (F5) or chimeric fibers (F5/50) comprising the tail of F5 and the fiber shaft and knob of HAdV serotype 50 (HAdV50). The CD46‐interacting chimeric fibers allow for the high‐level transduction of various human primary cell types of clinical interest with low or no surface expression of the Coxsackievirus and adenovirus receptor.ResultsA new set of pAdEasy plasmid ‘backbones’ with or without E2A and encoding F5 or F5/50 was constructed and recombined in E. coli strain BJ5183 with a ‘shuttle’ plasmid coding for β‐galactosidase. The resulting clones yielded AdV preparations with similar high titers following their rescue and propagation in producer cells. The AdVs with F5/50 were superior to those carrying F5 with respect to transducing human skeletal myocytes and mesenchymal stem cells.ConclusionsIn the present study, an AdEasy system tailored for the production of not only first‐, but also second‐generation AdVs equipped with the receptor‐interacting fiber domains of the prototypic species C HAdV5 or of the species B member HAdV50 is presented. This system expands the range of applications for this robust and versatile AdV production platform. Copyright © 2012 John Wiley & Sons, Ltd.
Alterations in local thyroid hormone signaling in the hippocampus of the SAMP8 mouse at younger ages: Association with delayed myelination and behavioral abnormalities
Authors: Sawano Erika , Negishi Takayuki , Aoki Tomoyuki , Murakami Masami , Tashiro Tomoko 
Published: December 2012

AbstractThe senescence‐accelerated mouse (SAM) strains were established through selective inbreeding of the AKR/J strain based on phenotypic variations of aging and consist of senescence‐prone (SAMP) and senescence‐resistant (SAMR) strains. Among them, SAMP8 is considered as a model of neurodegeneration displaying age‐associated learning and memory impairment and altered emotional status. Because adult hypothyroidism is one of the common causes of cognitive impairment and various psychiatric disorders, we examined the possible involvement of thyroid hormone (TH) signaling in the pathological aging of SAMP8 using the senescence‐resistant SAMR1 as control. Although plasma TH levels were similar in both strains, a significant decrease in type 2 deiodinase (D2) gene expression was observed in the SAMP8 hippocampus from 1 to 8 months of age, which led to a 35–50% reductions at the protein level and 20% reduction of its enzyme activity at 1, 3, and 5 months. D2 is responsible for local conversion of thyroxine into transcriptionally active 3,5,3′‐triiodothyronine (T3), so the results suggest a reduction in T3 level in the SAMP8 hippocampus. Attenuation of local TH signaling was confirmed by downregulation of TH‐dependent genes and by immunohistochemical demonstration of delayed and reduced accumulation of myelin basic protein, the expression of which is highly dependent on TH. Furthermore, we found that hyperactivity and reduced anxiety were not age‐associated but were characteristic of young SAMP8 before they start showing impairments in learning and memory. Early alterations in local TH signaling may thus underlie behavioral abnormalities as well as the pathological aging of SAMP8. © 2012 Wiley Periodicals, Inc.
Heterozygote deficiencies caused by a Wahlund effect: Dispelling unfounded expectations
Authors: Dharmarajan Guha , Beatty William S. , Rhodes Olin E. 
Published: December 2012

AbstractPopulation genetic tools can facilitate successful conservation and management of wildlife populations. However, the ability of such approaches to inform wildlife management and conservation programs depends upon assumptions linking genetic patterns to ecological processes, one implicit assumption usually being that genetic parameters (e.g., population genetic differentiation) estimated using a set of loci accurately reflect underlying demographic and microevolutionary forces affecting the population(s) under study. This is an important assumption because it also implies that we have acknowledged that genetic parameters estimated by a set of target loci inherently are associated with a sampling variance. Specifically, a perception exists that heterozygote deficits caused by biological mechanisms (e.g., a Wahlund effect) and null alleles can be differentiated by the expectation that the former leads to a concordant pattern across all loci, whereas the latter leads to locus‐specific effects. We use Monte‐Carlo simulation to demonstrate that these expectations do not always hold under biologically realistic conditions. Our analyses indicate that the conservative approach of discarding loci deviating from Hardy‐Weinberg equilibrium expectations could rob us of our most informative markers, weakening our ability to interpret biological phenomena. © 2012 The Wildlife Society.