bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetal adaptations for viviparity in amphibians
Authors: Wake Marvalee H.
Published: March 2014

Live‐bearing has evolved in all three orders of amphibians—frogs, salamanders, and caecilians. Developing young may be either yolk dependent, or maternal nutrients may be supplied after yolk is resorbed, depending on the species. Among frogs, embryos in two distantly related lineages develop in the skin of the maternal parents' backs; they are born either as advanced larvae or fully metamorphosed froglets, depending on the species. In other frogs, and in salamanders and caecilians, viviparity is intraoviductal; one lineage of salamanders includes species that are yolk dependent and born either as larvae or metamorphs, or that practice cannibalism and are born as metamorphs. Live‐bearing caecilians all, so far as is known, exhaust yolk before hatching and mothers provide nutrients during the rest of the relatively long gestation period. The developing young that have maternal nutrition have a number of heterochronic changes, such as precocious development of the feeding apparatus and the gut. Furthermore, several of the fetal adaptations, such as a specialized dentition and a prolonged metamorphosis, are homoplasious and present in members of two or all three of the amphibian orders. At the same time, we know little about the developmental and functional bases for fetal adaptations, and less about the factors that drive their evolution and facilitate their maintenance. J. Morphol. 276:941–960, 2015. © 2014 Wiley Periodicals, Inc.
Zwitterionic chiral stationary phases based on cinchona and chiral sulfonic acids for the direct stereoselective separation of amino acids and other amphoteric compounds
Authors: Zhang Tong , Holder Emilie , Franco Pilar , Lindner Wolfgang
Published: March 2014

An extensive series of free amino acids and analogs were directly resolved into enantiomers (and stereoisomers where appropriate) by HPLC on zwitterionic chiral stationary phases (Chiralpak ZWIX(+) and Chiralpak ZWIX(−)). The interaction and chiral recognition mechanisms were based on the synergistic double ion‐paring process between the analyte and the chiral selectors. The chiral separation and elution order were found to be predictable for primary α‐amino acids with apolar aliphatic side chains. A systematic investigation was undertaken to gain an insight into the influence of the structural features on the enantiorecognition. The presence of polar and/or aromatic groups in the analyte structure is believed to tune the double ion‐paring equilibrium by the involvement of the secondary interaction forces such as hydrogen bonding, Van der Waals forces and π–π stacking in concert with steric parameters. The ZWIX chiral columns were able to separate enantiomers and stereoisomers of various amphoteric compounds with no need for precolumn derivatization. Column switching between ZWIX(+) and ZWIX(−) is believed to be an instrumental tool to reverse or control the enantiomers elution order, due to the complementarity of the applied chiral selectors.
Nonutilitarian Tourism Destination Positioning: A Case Study in China
Authors: Qu Ying , Qu Hailin
Published: March 2014

This paper develops and applies a conceptual model of nonutilitarian tourism destination positioning. Tourist's nonutilitarian decision mechanisms (affective choosing and self‐congruity) are linked with destination positioning. A repositioning case of Dalian as a marine city destination versus its four competitors is used to demonstrate the model's guiding value. Through statistical analyses of MANOVA, ANOVAs and independent t‐tests, the findings indicate the differentiating affective image attribute and brand personality trait most useful for Dalian's positioning. A suggested nonutilitarian positioning strategy for Dalian, corresponding managerial and theoretical implications and future study considerations are finally summarized. Copyright © 2014 John Wiley & Sons, Ltd.
New Perspectives of HPMA‐based Copolymers Derived by Post‐Polymerization Modification
Authors: Nuhn Lutz , Barz Matthias , Zentel Rudolf
Published: March 2014

Poly[N‐(2‐hydroxypropyl) methacrylamide] (HPMA) was one of the first polymers applied as polymer drug conjugate in the clinics. Since then many attempts have been made to expand the functionality of HPMA‐based copolymers from advanced synthetic pathways to multiple biomedical applications. This Feature Article highlights multifunctional HPMA based copolymers prepared by controlled radical polymerization and subsequent post‐polymerization modification of activated ester precursor polymers via aminolysis. This approach combines precise control of the polymer's microstructure (molecular weight, dispersity, block copolymer formation, end group functionalization) with an easy introduction of various multifunctional groups. The obtained polymers can be used as versatile targeted drug carriers for sophisticated molecular imaging techniques that provide detailed information about structure property relationships both in vitro as well as in vivo. Moreover, recent studies have shown that such multifunctional HPMA copolymers may have high potential as advanced carriers in the field of tumor immunotherapy.
An EPR study of the radical addition to 3‐nitropentan‐2‐one as an archetype of α‐carbonylnitroalkanes
Authors: Campredon Mylène , Alberti Angelo
Published: March 2014

Carbon, silicon, germanium, tin and lead‐centered radicals were reacted with 3‐nitropentan‐2‐one and 3‐nitropentan‐2‐ol inside the cavity of an electron paramagnetic resonance spectrometer. In all cases, selective addition to the nitrogroup was observed with detection of the corresponding oxynitroxide radicals. In the case of the carbonyl substrate, alkyl acyl nitroxides were also detected because of α‐photocleavage. The oxynitroxides decayed with a first order kinetics via fragmentation of the carbon–nitrogen bond (denitration). Unexpectedly, the activation parameters were fairly similar to those previously reported for the corresponding tert‐butyl oxynitroxides and almost independent from the presence of a carbonyl or a hydroxyl group on the carbon adjacent to the one bearing the nitrogroup. Copyright © 2014 John Wiley & Sons, Ltd.
Rapid and accurate T2 mapping from multi–spin‐echo data using Bloch‐simulation‐based reconstruction
Authors: Ben‐Eliezer Noam , Sodickson Daniel K. , Block Kai Tobias
Published: March 2014

Purpose

Quantitative T2‐relaxation‐based contrast has the potential to provide valuable clinical information. Practical T2‐mapping, however, is impaired either by prohibitively long acquisition times or by contamination of fast multiecho protocols by stimulated and indirect echoes. This work presents a novel postprocessing approach aiming to overcome the common penalties associated with multiecho protocols, and enabling rapid and accurate mapping of T2 relaxation values.

Methods

Bloch simulations are used to estimate the actual echo‐modulation curve (EMC) in a multi–spin‐echo experiment. Simulations are repeated for a range of T2 values and transmit field scales, yielding a database of simulated EMCs, which is then used to identify the T2 value whose EMC most closely matches the experimentally measured data at each voxel.

Results

T2 maps of both phantom and in vivo scans were successfully reconstructed, closely matching maps produced from single spin‐echo data. Results were consistent over the physiological range of T2 values and across different experimental settings.

Conclusion

The proposed technique allows accurate T2 mapping in clinically feasible scan times, free of user‐ and scanner‐dependent variations, while providing a comprehensive framework that can be extended to model other parameters (e.g., T1, B1+, B0, diffusion) and support arbitrary acquisition schemes. Magn Reson Med 73:809–817, 2015. © 2014 Wiley Periodicals, Inc.
Identification of anticancer drugs for hepatocellular carcinoma through personalized genome‐scale metabolic modeling
Authors: Agren Rasmus , Mardinoglu Adil , Asplund Anna , Kampf Caroline , Uhlen Mathias , Nielsen Jens
Published: March 2014

Genome‐scale metabolic models (GEMs) have proven useful as scaffolds for the integration of omics data for understanding the genotype–phenotype relationship in a mechanistic manner. Here, we evaluated the presence/absence of proteins encoded by 15,841 genes in 27 hepatocellular carcinoma (HCC) patients using immunohistochemistry. We used this information to reconstruct personalized GEMs for six HCC patients based on the proteomics data, HMR 2.0, and a task‐driven model reconstruction algorithm (tINIT). The personalized GEMs were employed to identify anticancer drugs using the concept of antimetabolites; i.e., drugs that are structural analogs to metabolites. The toxicity of each antimetabolite was predicted by assessing the in silico functionality of 83 healthy cell type‐specific GEMs, which were also reconstructed with the tINIT algorithm. We predicted 101 antimetabolites that could be effective in preventing tumor growth in all HCC patients, and 46 antimetabolites which were specific to individual patients. Twenty‐two of the 101 predicted antimetabolites have already been used in different cancer treatment strategies, while the remaining antimetabolites represent new potential drugs. Finally, one of the identified targets was validated experimentally, and it was confirmed to attenuate growth of the HepG2 cell line.
Two‐way coupling in reservoir–geomechanical models: vertex‐centered Galerkin geomechanical model cell‐centered and vertex‐centered finite volume reservoir models
Authors: Prevost Jean H.
Published: March 2014

Procedures to couple reservoir and geomechanical models are reviewed. The focus is on immiscible compressible non‐compositional reservoir–geomechanical models. Such models require the solution to: coupled stress, pressure, saturation and temperature equations. Although the couplings between saturation and temperature with stress and fluid pressure are ‘weak’ and can be adequately captured thru staggered (fixed point) iterations, the couplings between stress and pressure are ‘strong’ and require special procedures for accurate integration. As shown and discussed in detail in our previous works, two‐way coupling (i.e., simultaneous integration) of pressure and stress equations is required if poromechanical effects are to be captured accurately. In our previous work, a Galerkin implementation of both pressure and stress equations was used with equal order interpolants.

However, most (if not all) reservoir simulators use a finite volume implementation of the pressure equation. Therefore, there remain important unanswered questions related to the interface between a Galerkin vertex‐centered geomechanical model with a reservoir finite volume model as such an implementation has never been attempted before. We address those issues in the following by studying the interface with both a cell‐centered and a vertex‐centered finite volume implementation of the pressure equation. Central to the success of the implementation is the computation of the Jacobian matrix. The elemental contribution to the coupling Jacobian matrix is computed through numerical finite differencing of the residuals. The procedure is detailed herein. In the following, in order to attempt to clear confusion, the simplest case of an isothermal fully saturated, slightly compressible system is presented in detail, and the various solution strategies, simplifications and shortcomings are identified. Copyright © 2014 John Wiley & Sons, Ltd.
hp–Adaptive composite discontinuous Galerkin methods for elliptic problems on complicated domains
Authors: Giani Stefano , Houston Paul
Published: March 2014

In this article, we develop the a posteriori error estimation of hp–version discontinuous Galerkin composite finite element methods for the discretization of second‐order elliptic partial differential equations. This class of methods allows for the approximation of problems posed on computational domains which may contain a huge number of local geometrical features, or microstructures. Although standard numerical methods can be devised for such problems, the computational effort may be extremely high, as the minimal number of elements needed to represent the underlying domain can be very large. In contrast, the minimal dimension of the underlying composite finite element space is independent of the number of geometric features. Computable bounds on the error measured in terms of a natural (mesh‐dependent) energy norm are derived. Numerical experiments highlighting the practical application of the proposed estimators within an automatic hp–adaptive refinement procedure will be presented. © 2014 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 30: 1342–1367, 2014
Effect of Caffeinated Versus Noncaffeinated Energy Drinks on Central Blood Pressures
Authors: Phan Jennifer K. , Shah Sachin A.
Published: March 2014

Study Objective

To evaluate the effects of caffeinated energy shots compared with noncaffeinated energy shots as assessed by changes in peripheral and central hemodynamic parameters in healthy subjects.

Design

Randomized, double‐blind, controlled crossover study.

Setting

University campus.

Patients

Ten healthy volunteers.

Measurements and Main Results

Subjects were randomized to receive either a caffeinated or noncaffeinated energy shot; after a minimum 6 days washout period, subjects were given the alternate energy shot. Peripheral blood pressures, and central hemodynamic parameters, were assessed and recorded for each subject at baseline and at 1 and 3 hours after consumption of the energy shots. Peripheral systolic blood pressure (SBP) increased significantly with the caffeinated energy shot compared with noncaffeinated (8.30 ± 4.19 mm Hg and −0.20 ± 5.55, respectively, p=0.009) at 3 hours. Central SBP increased significantly with the caffeinated energy shot compared with noncaffeinated (8.00 ± 4.03 mm Hg and 1.50 ± 6.57, respectively, p=0.045) at 3 hours. Peripheral and central diastolic blood pressure were nonsignificantly higher with the caffeinated energy shot at 3 hours. Peripheral and central pulse pressure were consistently higher with consumption of the caffeinated beverage. Heart rate, augmentation index, pulse pressure amplification ratio, ejection duration and Subendocardial Viability Ratio were not different between the two interventions over time. P1 height was significantly higher with the caffeinated shot compared with the noncaffeinated shot at both 1 and 3 hours (p=0.035 and 0.013, respectively). Three and one subjects experienced an adverse effect with the caffeinated and noncaffeinated shot, respectively.

Conclusion

A caffeinated energy shot acutely increases peripheral and central SBPs compared with a noncaffeinated energy shot. Larger studies with a placebo comparator are needed to assess the significance of peripheral and central hemodynamic changes with noncaffeinated energy drinks.
Microwave Plasma Process for SiCN:H Thin Films Synthesis with Composition Varying from SiC:H to SiN:H in H2/N2/Ar/Hexamethyldisilazane Gas Mixture
Authors: Belmahi Mohammed , Bulou Simon , Thouvenin Amanda , de Poucques Ludovic , Hugon Robert , Le Brizoual Laurent , Miska Patrice , Genève Damien , Vasseur Jean‐Luc , Bougdira Jamal
Published: March 2014

SiCxNy:H thin films are obtained with the microwave plasma assisted chemical vapour deposition (MPACVD) method in the gas mixture H2/Ar/Hexamethyldisilazane. When very few amounts of nitrogen are added to the gas mixture, the film composition changes drastically from SiCx:H like films to SiNx:H like films, according to X‐rays Photoelectron Spectroscopy and Fourier Transform Infra‐Red Spectroscopy (FTIR) analysis. The refractive index (n) and Tauc's optical gap (Eg) are modified over a wide range of values (1.75 ≤ n ≤ 2.15 and 3.5 eV ≤ Eg ≤ 5 eV) with nitrogen addition to the feed gas leading to thin films optical constants close to those of SiC or Si3N4. Therefore, for the films obtained without nitrogen, SiC nanoparticles with a size of about 20 nm embedded in an amorphous SiCN:H matrix are synthesized, leading to nanocomposite films.
Photoreflectance study of the temperature dependence of excitonic transitions in dilute GaAsN alloys
Authors: Okubo Wataru , Yagi Shuhei , Hijikata Yasuto , Onabe Kentaro , Yaguchi Hiroyuki
Published: March 2014

We have studied the temperature dependence of optical transitions in dilute GaAsN alloys using photoreflectance (PR). A delocalized‐state transition is clearly observed in PR spectra while several localized‐state emission lines due to isoelectronic centers appear in photoluminescence spectra. The energy of optical transitions observed in PR spectra is in agreement with the excitonic transition energy in photoluminescence excitation spectra, clearly showing that the optical transitions in PR spectra are excitonic transitions. We analyzed the temperature dependence of the excitonic transition energies using the Bose–Einstein statistical expression, and found that even dilute alloys follow the same trend as GaAsN alloys with higher nitrogen concentrations. We discuss the coexistence of localized and delocalized states in dilute GaAsN alloys in terms of the random distribution of N atoms.
Low‐temperature stimulated Raman scattering spectroscopy of tetragonal GdVO4 single crystals
Authors: Kaminskii A. A. , Lux O. , Rhee H. , Kaltenbach A. , Eichler H. J. , Zhang J. , Tang D. Y. , Yu H. , Zhang H. , Wang J. , Yoneda H. , Ueda K. , Shirakawa A.
Published: March 2014

We report on the results of low‐temperature stimulated Raman scattering (SRS)‐spectroscopy of tetragonal GdVO4 single crystals. Measurements at T ≈ 9 K and picosecond excitation in the visible and near‐infrared range revealed new manifestations of χ(3)‐nonlinear photon–phonon interactions. Besides many‐phonon Stokes and anti‐Stokes octave spanning SRS generation we discovered a new fundamental χ(3)‐active phonon mode of the crystal. Furthermore, we received data on combined SRS‐active vibrational modes. The lower limits of the steady‐state Raman gain coefficients for first Stokes generation have been estimated together with the temperature dependence of these values in the range from T ≈ 9 and 273 K. A short review of SRS‐promoting vibrational modes and manifestations of χ(3)‐nonlinear interactions of all known SRS‐active tetragonal rare‐earth REVO4 vanadates is given as well.
Optical detection of nonradiative recombination centers in AlGaN quantum wells for deep UV region
Authors: Touhidul Islam A. Z. M. , Murakoshi N. , Fukuda T. , Hirayama H. , Kamata N.
Published: March 2014

By superposing a chopped below‐gap excitation (BGE) light on a cw above‐gap excitation and observing the intensity change of photoluminescence (PL) due to the BGE, we clarified a distribution of nonradiative recombination (NRR) centers in AlGaN multi‐quantum well (MQW) structures for the wavelength region of deep ultraviolet (UV). The decrease in band‐edge PL peak intensity at 10 K exemplified the presence of a pair of NRR centers in AlGaN well layers whose transition energy corresponds to that of the BGE. The BGE power dependence of the normalized PL intensity showed a quenching saturation due to trap‐filling effect of electrons in one of the centers which were activated by the BGE. The BGE energy dependence of the normalized PL intensity revealed that the optical activation energy of the dominant NRR process via these trap states in the AlGaN MQW is around 1.17 eV. The purely optical scheme of detection enables us to obtain clues for identifying defect levels in DUV region and eliminating them during growth process without any preparation of electrodes. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Strain states in GaN films grown on Si(111) and Si(110) substrates using a thin AlN/GaN superlattice interlayer
Authors: Shen X. Q. , Takahashi T. , Ide T. , Shimizu M.
Published: March 2014

We report the characterization results of the strain states in GaN films grown both on Si(111) and Si(110) substrates by applying a thin AlN/GaN superlattice structure (SLs) as an interlayer (IL). The strain states in the GaN films grown on Si(111) and Si(110) substrates are compared. It is demonstrated that the modulation effect by the SL ILs on the strain state in the GaN film is universal although different behaviours on the Si(111) and Si(110) substrate are observed due to the different lattice symmetry relationship between the substrate and the epilayer. By using the technique, we succeeded in growing thick continuous GaN films (> 3 µm), which are necessary for the high‐power, high‐voltage device applications. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Fourier transform infrared spectroscopy analysis of thin boron nitride films prepared by ion beam assisted deposition
Authors: Matsuoka Masao , Langhi Mauro P. , Isotani Sadao , Chubaci José F. D.
Published: March 2014

Thin boron nitride (BN) films were synthesized by ion beam assisted deposition (IBAD). From Fourier transform infrared spectroscopy (FTIR) analysis results, it was found that: the films with the co‐presence of explosion‐phase BN (E‐BN) and sp2‐bonded hexagonal BN (h‐BN), and those with pure h‐BN were formed in the respective substrate temperature regions of 20–85 °C and 350–400 °C, under nitrogen ion irradiation (ion energy from 500 to 1000 eV), while the substrate temperature at 400 °C and mixed nitrogen and argon ion irradiation were necessary for the formation of sp3‐bonded cubic BN (c‐BN). To our knowledge, the E‐BN phase was formed firstly by IBAD in this study. The crystalline phase identification through the FTIR results was in line with X‐ray diffraction results. The shift of the c‐BN peak position is usually attributed to remaining compressive stress in the film. In this work, the downward shift of the c‐BN peak position and the broadening of the c‐BN peak, which were observed when the film thickness increased, can be interpreted using a phenomenological description of structural disordering in the c‐BN sites. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Projected Risk of Population Declines for Native Fish Species in the Upper Mississippi River
Authors: Crimmins S. M. , Boma P. , Thogmartin W. E.
Published: March 2014

Conservationists are in need of objective metrics for prioritizing the management of habitats. For individual species, the threat of extinction is often used to prioritize what species are in need of conservation action. Using long‐term monitoring data, we applied a Bayesian diffusion approximation to estimate quasi‐extinction risk for 54 native fish species within six commercial navigation reaches along a 1350‐km gradient of the upper Mississippi River system. We found a strong negative linear relationship between quasi‐extinction risk and distance upstream. For some species, quasi‐extinction estimates ranged from nearly zero in some reaches to one in others, suggesting substantial variability in threats facing individual river reaches. We found no evidence that species traits affected quasi‐extinction risk across the entire system. Our results indicate that fishes within the upper Mississippi River system face localized threats that vary across river impact gradients. This suggests that conservation actions should be focused on local habitat scales but should also consider the additive effects on downstream conditions. We also emphasize the need for identification of proximate mechanisms behind observed and predicted population declines, as conservation actions will require mitigation of such mechanisms. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Concise Review: Fragile X Proteins in Stem Cell Maintenance and Differentiation
Authors: Li Yue , Zhao Xinyu
Published: March 2014

Fragile X syndrome (FXS), the most common genetic form of autism spectrum disorder, is caused by deficiency of the fragile X mental retardation protein (FMRP). Despite extensive research and scientific progress, understanding how FMRP regulates brain development and function remains a major challenge. FMRP is a neuronal RNA-binding protein that binds about a third of messenger RNAs in the brain and controls their translation, stability, and cellular localization. The absence of FMRP results in increased protein synthesis, leading to enhanced signaling in a number of intracellular pathways, including the mTOR, mGLuR5, ERK, Gsk3β, PI3K, and insulin pathways. Until recently, FXS was largely considered a deficit of mature neurons; however, a number of new studies have shown that FMRP may also play important roles in stem cells, among them neural stem cells, germline stem cells, and pluripotent stem cells. In this review, we will cover these newly discovered functions of FMRP, as well as the other two fragile X-related proteins, in stem cells. We will also discuss the literature on the use of stem cells, particularly neural stem cells and induced pluripotent stem cells, as model systems for studying the functions of FMRP in neuronal development. Stem Cells  2014;32:1724–1733
miR-335 Correlates with Senescence/Aging in Human Mesenchymal Stem Cells and Inhibits Their Therapeutic Actions Through Inhibition of AP-1 Activity
Authors: Tomé María , Sepúlveda Juan Carlos , Delgado Mario , Andrades José A. , Campisi Judith , González, Manuel A. , Bernad Antonio
Published: March 2014

MicroRNAs, small noncoding RNAs, regulate gene expression primarily at the posttranscriptional level. We previously found that miR-335 is critically involved in the regulation and differentiation capacity of human mesenchymal stem cells (hMSCs) in vitro. In this study, we investigated the significance of miR-335 for the therapeutic potential of hMSCs. Analysis of hMSCs in ex vivo culture demonstrated a significant and progressive increase in miR-335 that is prevented by telomerase. Expression levels of miR-335 were also positively correlated with donor age of hMSCs, and were increased by stimuli that induce cell senescence, such as γ-irradiation and standard O2 concentration. Forced expression of miR-335 resulted in early senescence-like alterations in hMSCs, including: increased SA-β-gal activity and cell size, reduced cell proliferation capacity, augmented levels of p16 protein, and the development of a senescence-associated secretory phenotype. Furthermore, overexpression of miR-335 abolished the in vivo chondro-osseous potential of hMSCs, and disabled their immunomodulatory capacity in a murine experimental model of lethal endotoxemia. These effects were accompanied by a severely reduced capacity for cell migration in response to proinflammatory signals and a marked reduction in Protein Kinase D1 phosphorylation, resulting in a pronounced decrease of AP-1 activity. Our results demonstrate that miR-335 plays a key role in the regulation of reparative activities of hMSCs and suggests that it might be considered a marker for the therapeutic potency of these cells in clinical applications. Stem Cells  2014;32:2229–2244
Gremlin 2 Promotes Differentiation of Embryonic Stem Cells to Atrial Fate by Activation of the JNK Signaling Pathway
Authors: Tanwar Vineeta , Bylund Jeffery B. , Hu Jianyong , Yan Jingbo , Walthall Joel M. , Mukherjee Amrita , Heaton William H. , Wang Wen-Der , Potet Franck , Rai Meena , Kupershmidt Sabina , Knapik Ela W. , Hatzopoulos Antonis K.
Published: March 2014

The bone morphogenetic protein antagonist Gremlin 2 (Grem2) is required for atrial differentiation and establishment of cardiac rhythm during embryonic development. A human Grem2 variant has been associated with familial atrial fibrillation, suggesting that abnormal Grem2 activity causes arrhythmias. However, it is not known how Grem2 integrates into signaling pathways to direct atrial cardiomyocyte differentiation. Here, we demonstrate that Grem2 expression is induced concurrently with the emergence of cardiovascular progenitor cells during differentiation of mouse embryonic stem cells (ESCs). Grem2 exposure enhances the cardiogenic potential of ESCs by 20–120-fold, preferentially inducing genes expressed in atrial myocytes such as Myl7, Nppa, and Sarcolipin. We show that Grem2 acts upstream to upregulate proatrial transcription factors CoupTFII and Hey1 and downregulate atrial fate repressors Irx4 and Hey2. The molecular phenotype of Grem2-induced atrial cardiomyocytes was further supported by induction of ion channels encoded by Kcnj3, Kcnj5, and Cacna1d genes and establishment of atrial-like action potentials shown by electrophysiological recordings. We show that promotion of atrial-like cardiomyocytes is specific to the Gremlin subfamily of BMP antagonists. Grem2 proatrial differentiation activity is conveyed by noncanonical BMP signaling through phosphorylation of JNK and can be reversed by specific JNK inhibitors, but not by dorsomorphin, an inhibitor of canonical BMP signaling. Taken together, our data provide novel mechanistic insights into atrial cardiomyocyte differentiation from pluripotent stem cells and will assist the development of future approaches to study and treat arrhythmias. Stem Cells  2014;32:1774–1788
Coactivators p300 and CBP Maintain the Identity of Mouse Embryonic Stem Cells by Mediating Long-Range Chromatin Structure
Authors: Fang Fang , Xu Yifeng , Chew Kai-Khen , Chen Xi , Ng Huck-Hui , Matsudaira Paul
Published: March 2014

Master transcription factors Oct4, Sox2, and Nanog are required to maintain the pluripotency and self-renewal of embryonic stem cells (ESCs) by regulating a specific transcriptional network. A few other transcription factors have been shown to be important in ESCs by interacting with these master transcription factors; however, little is known about the transcriptional mechanisms regulated by coregulators (coactivators and corepressors). In this study, we examined the function of two highly homologous coactivators, p300 and CREB-binding protein (CBP), in ESCs. We find that these two coactivators play redundant roles in maintaining the undifferentiated state of ESCs. They are recruited by Nanog through physical interaction to Nanog binding loci, mediating the formation of long-range chromatin looping structures, which is essential to maintain ESC-specific gene expression. Further functional studies reveal that the p300/CBP binding looping fragments contain enhancer activities, suggesting that the formation of p300/CBP-mediated looping structures may recruit distal enhancers to create a concentration of factors for the transcription activation of genes that are involved in self-renewal and pluripotency. Overall, these results provide a total new insight into the transcriptional regulation mechanism of coactivators p300 and CBP in ESCs, which is important in maintaining self-renewal and pluripotency, by mediating the formation of higher order chromosome structures. Stem Cells  2014;32:1805–1816
Accounting for the Performance of Environmentally Significant Behavior: The Symbolic Significance of Recycling
Authors: Markle Gail
Published: March 2014

The scientific community has pronounced climate change unequivocal and its consequences disastrous. Yet Americans' behavioral response to the global social problem of environmental degradation has been largely confined to the individual act of recycling. This article examines why Americans are not doing more to address climate change and other environmental issues. Taking a cognitive sociological perspective, I describe how Americans think about environmental issues and pro‐environmental behavior. I draw on Swidler's concept of a “cultural tool kit,” to examine the cultural narratives Americans use to account for the small amount of pro‐environmental behavior they perform. The act of recycling functions as a synecdoche for pro‐environmental behavior in general, allowing individuals to over‐claim the significance of a modest amount of pro‐environmental behavior. I argue that Americans' failure to engage with environmental issues at a collective level is rooted in the individualized culture of American environmentalism.
How to make sense of our rivers: using assemblage to understand angling
Authors: Bracken Louise J. , Oughton Elizabeth
Published: March 2014

Our freshwater habitats are under threat and governance of these systems is rapidly evolving. It is thus important to examine how we make sense of our rivers and how this understanding can underpin catchment management. Assemblage is one approach that can be used to understand our freshwater environments. In this article we reflect on an interdisciplinary project on angling to evaluate whether using assemblage may help us comprehend our rivers in new ways. We work through themes of: different perspectives of river processes, what constitutes evidence used in decision making, how the nexus between wildlife and the physical environment plays out, and the importance of rivers to our well‐being. We demonstrate how assemblage can facilitate a deeper and more comprehensive understanding of relational processes and how these evolve over time. Assemblage can thus be used as a way of exploring rivers to support integrated management within complex systems of governance.

This article is categorized under:

Water and Life > Conservation, Management, and Awareness

Human Water > Water Governance
Audience segmentation and climate change communication: conceptual and methodological considerations
Authors: Hine Donald W , Reser Joseph P , Morrison Mark , Phillips Wendy J , Nunn Patrick , Cooksey Ray
Published: March 2014

Engaging the public about mitigating or adapting to climate change threats poses significant challenges for scientists, policy makers, and others responsible for developing communication strategies. In response to these challenges, interest is growing in audience segmentation as a possible strategy to develop more effective communications that are tailored and targeted to subgroups of the public who share similar values, beliefs, behaviors, and/or policy preferences about climate change. In this article, we provide a brief historical overview of audience segmentation and its applications to marketing, health, politics, and most recently climate change. We then critically evaluate several conceptual arguments about whether segmentation is an appropriate strategy for climate change communications, review key methodological considerations associated with conducting segmentation analyses, and make several recommendations about best practice. We conclude that, in principle, audience segmentation and targeted messaging are potentially valuable tools for enhancing climate change communication. But, in practice, there are conceptual and methodological complexities of which practitioners and consumers should be aware when conducting and interpreting the results of segmentation studies. In addition, more research is required, particularly related to tailoring and targeting messages to identified segments, before these strategies can be considered to have a sufficient evidence base to warrant widespread adoption.

This article is categorized under:

Perceptions, Behavior, and Communication of Climate Change > Perceptions of Climate Change
Climate change mitigation policies and poverty
Authors: Barbier Edward B
Published: March 2014

Climate change mitigation policies include a wide range of actions, including efforts to reduce greenhouse gas (GHG) emissions from fossil fuel combustion, energy efficiency and end‐use innovations, and reducing carbon emissions through avoided deforestation. Such policies can affect poverty in developing countries either directly or indirectly. Direct impacts on poverty include payments for avoided deforestation that affect the livelihoods of the poor, reduced GHG emissions that also produce co‐benefits of improved air quality and health, and clean energy and energy efficiency effects on energy poverty. Indirect impacts on the poor in developing countries occur through the changes in trade, economic growth, and other economy‐wide effects. To date, there is a lack of systematic or comprehensive analyses of these direct and indirect impacts of mitigation policies on the poor. Although such policies may benefit the poor, some actions may worsen poverty and hinder its alleviation. This suggests that a more comprehensive approach should be employed in analyzing how mitigation policies affect the poor in developing countries, and in particular, in assessing how policy design and implementation can influence the potential trade‐offs between the positive and negative impacts on poverty alleviation.

This article is categorized under:

Climate Economics > Economics and Climate Change

Climate and Development > Social Justice and the Politics of Development
Drug discovery and the maze of biological complexity: an editorial essay
Authors: Subramaniam Shankar
Published: March 2014

This article is categorized under:

Biological Mechanisms > Chemical Biology
Tactile sensory system: encoding from the periphery to the cortex
Authors: Jones Lynette A. , Smith Allan M.
Published: March 2014

Specialized mechanoreceptors in the skin respond to mechanical deformation and provide the primary input to the tactile sensory system. Although the morphology of these receptors has been documented, there is still considerable uncertainty as to the relation between cutaneous receptor morphology and the associated physiological responses to stimulation. Labelled‐line models of somatosensory processes in which specific mechanoreceptors are associated with particular sensory qualities fail to account for the evidence showing that all types of tactile afferent units respond to a varying extent to most types of natural stimuli. Neurophysiological and psychophysical experiments have provided the framework for determining the relation between peripheral afferent or cortical activity and tactile perception. Neural codes derived from these afferent signals are evaluated in terms of their capacity to predict human perceptual performance. One particular challenge in developing models of the tactile sensory system is the dual use of sensory signals from the skin. In addition to their perceptual function they serve as inputs to the sensorimotor control system involved in manipulation. Perceptions generated through active touch differ from those resulting from passive stimulation of the skin because they are the product of self‐generated exploratory processes. Recent research in this area has highlighted the importance of shear forces in these exploratory movements and has shown that fingertip skin is particularly sensitive to shear generated during both object manipulation and tactile exploration.

This article is categorized under:

Models of Systems Properties and Processes > Organismal Models

Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models

Physiology > Physiology of Model Organisms
Two Coordination Polymers with the Ligand Salicylamide: Synthesis, Crystal Structure and Luminescent Properties
Authors: Song Xueqin , Xiao Zhourong , Zhao Mengmeng , Qian Wenhui
Published: March 2014

The semirigid exo‐bidentate ligand 1, 4‐bis{[(2′‐picolylaminoformyl)phenoxyl]methyl}‐2, 5‐bismethylbenzene (L) was designed, synthesized, and used as building blocks for constructing luminescent lanthanide polymers. Two new lanthanide coordination polymers were characterized by elemental analysis, X‐ray diffraction analysis, and IR spectroscopy. The coordination polymers exhibit the metal‐to‐ligand molar ratio of 1:1 and the semirigid exo‐bidentate ligand bridges lanthanide nitrates forming a zigzag chain, which further interconnected to three dimensional supramolecular structure in aid of cooperative C–H···O hydrogen bonds. The luminescence properties of the europium(III) complex are discussed in detail.
Management, winter climate and plant–soil feedbacks on ski slopes: a synthesis
Authors: Meijer zu Schlochtern Melanie P. , Rixen Christian , Wipf Sonja , Cornelissen Johannes H. C.
Published: March 2014

Owing to the increasing popularity of skiing and the upslope movement of the snow reliability line in mountain regions, more and more alpine environments are being turned into skiing areas, with strong impacts on ecosystem functions and biodiversity. Creation and management of ski slopes cause physical disturbance to soil and vegetation, while (artificial) snow supplements affect soil structure, chemistry, moisture and temperature regimes as well as shifts in snow season and growing season length. Vegetation–soil feedbacks may influence the outcome of these interactive effects on soil and vegetation, with possible consequences for soil erosion. Moreover, climate warming will lead to changing snow cover and duration, which will interact with ski slope management effects on soil and vegetation and its feedbacks. Based on a conceptual framework we review the main elements of these interactive effects on soil and vegetation on new and established ski slopes. We also set a research agenda with specific studies that could further advance our understanding of interacting ski slope management, winter climate, vegetation–soil feedbacks and ecosystem functioning. In such new investigations, alpine climate change ecology can probably learn much from the “experimental” disturbance and snow manipulations on ski slopes and vice versa.
Decolorization of Sapindus Pericarp Extract by Hydrogen Peroxide and a Comparison of Basic Characteristics Before and After Decolorization
Authors: Wang Na , Wang Heya , Weng Zhen , Zhang Cui , Wu Heng , Guo Youzhi , Sun Zhiyong , Yao Weirong
Published: March 2014

The saponins from the pericarps of Sapindus mukorossi Gaertn. (Sapindaceae) are attracting more and more attention because of their antimicrobial activity and their ability to act as a natural surfactant. However, the color of Sapindus pericarp extract is dark brown, which limits its application in some products. The present study aims to improve the color by adding hydrogen peroxide. An orthogonal L9 (3)4 test design was applied to optimize the decolorization parameters, including the amount of added hydrogen peroxide, time, temperature and pH. The extent of decolorization was up to 89.5 % below 80 °C within 80 min, using 2.5 % hydrogen peroxide at pH 6. The characteristics of Sapindus pericarp extract before and after bleaching were compared, including the antimicrobial and foaming performance, surface activities and detergency properties. There was no significant difference in either the diameters of the inhibition zone or the minimum inhibitory concentration against Candida albicans, Trichophyton rubrum and Pseudomonas aeruginosa (P < 0.05), while these parameters for C. albicans, T. rubrum and P. aeruginosa for the sample after decolorization were 22.33, 25.00, 15.33 mm and 0.91, 0.91, 13.03 mg/mL, respectively. The foamability of the Sapindus pericarp extract after decolorization was somewhat enhanced and the foam stability reduced (P < 0.05). There were no significant differences in values of the critical micelle concentration of the pericarp extract before and after decolorization. The detergency also remained at the same level. Our results show that the properties of the decolorized Sapindus pericarp extract were largely unchanged. This suggests that further development is worthwhile.
Attenuation of muscle wasting in murine C2C12 myotubes by epigallocatechin‐3‐gallate
Authors: Mirza Kamran A. , Pereira Suzette L. , Edens Neile K. , Tisdale Michael J.
Published: March 2014

Background

Loss of muscle protein is a common feature of wasting diseases where currently treatment is limited. This study investigates the potential of epigallocatechin‐3‐gallate (EGCg), the most abundant catechin in green tea, to reverse the increased protein degradation and rescue the decreased protein synthesis which leads to muscle atrophy.

Methods

Studies were conducted in vitro using murine C2C12 myotubes. Increased protein degradation and reduced rates of protein synthesis were induced by serum starvation and tumour necrosis factor‐α (TNF‐α).

Results

EGCg effectively attenuated the depression of protein synthesis and increase in protein degradation in murine myotubes at concentrations as low as 10 μM. Serum starvation increased expression of the proteasome 20S and 19S subunits, as well as the proteasome ‘chymotrypsin‐like' enzyme activity, and these were all attenuated down to basal values in the presence of EGCg. Serum starvation did not increase expression of the ubiquitin ligases MuRF1 and MAFbx, but EGCg reduced their expression below basal levels, possibly due to an increased expression of phospho Akt (pAkt) and phospho forkhead box O3a (pFoxO3a). Attenuation of protein degradation by EGCg was increased in the presence of ZnSO4, suggesting an EGCg‐Zn2+ complex may be the active species.

Conclusion

The ability of EGCg to attenuate depressed protein synthesis and increase protein degradation in the myotubule model system suggests that it may be effective in preserving skeletal muscle mass in catabolic conditions.
Potential role of antimicrobial peptides in the early onset of Alzheimer's disease
Authors: Welling Mick M. , Nabuurs Rob J.A. , van der Weerd Louise
Published: March 2014

Cerebral aggregation of amyloid‐β (Aβ) is thought to play a major role in the etiology of Alzheimer's disease. Environmental influences, including chronic bacterial or viral infections, are thought to alter the permeability of the blood‐brain barrier (BBB) and thereby facilitate cerebral colonization by opportunistic pathogens. This may eventually trigger Aβ overproduction and aggregation. Host biomolecules that target and combat these pathogens, for instance, antimicrobial peptides (AMPs) such as Aβ itself, are an interesting option for the detection and diagnostic follow‐up of such cerebral infections. As part of the innate immune system, AMPs are defensive peptides that efficiently penetrate infected cells and tissues beyond many endothelial barriers, most linings, including the BBB, and overall specifically target pathogens. Based on existing literature, we postulate a role for labeled AMPs as a marker to target pathogens that play a role in the aggregation of amyloid in the brain.
Revisiting the mixing-length hypothesis in the outer part of turbulent wall layers: mean flow and wall friction
Authors: Pirozzoli Sergio
Published: March 2014

We reconsider foundations and implications of the mixing length theory as applied to wall-bounded turbulent flows in uniform pressure gradient. Based on recent channel-flow direct numerical simulation (DNS) data at sufficiently high Reynolds number, we find that Prandtl’s hypothesis of linear variation of the mixing length with the wall distance is rather inaccurate, hence overlap arguments are stronger in justifying the formation of a logarithmic layer in the mean velocity profile. Regarding the core region of the wall layer, we find that Clauser’s hypothesis of uniform eddy viscosity is strictly connected with the observed size of the eddy structures, and it delivers surprisingly good agreement with DNS and experiments for channels, pipes, and boundary layers. We show that the analytically derived composite mean velocity profiles can be used to accurately predict skin friction in canonical wall-bounded flows with a minimal number of adjustable parameters directly related to the mean velocity profile, and to obtain some insight into transient growth phenomena.
Similarity solution for oblique water entry of an expanding paraboloid
Authors: Wu G. X. , Sun S. L.
Published: March 2014

Similarity solutions based on velocity potential theory are found to be possible in the case of an expanding paraboloid entering water when gravity is ignored. Numerical solutions are obtained based on the boundary element method. Iteration is used for the nonlinear boundary conditions on the unknown free surface, together with regular remeshing. Results are obtained for paraboloids with different slenderness (or bluntness). Flow features and pressure distributions are discussed along with the physical implications. It is also concluded that similarity solutions may be possible in more general cases.