bluuebunny/crossref_metadata_2025 huggingface dataset:
Tropical cyclone evolution in a minimal axisymmetric model revisited
Authors: Schmidt Christoph W. , Smith Roger K.
Published: January 2016

An improved version of a minimal model for a tropical cyclone is described. The model is used to revisit some fundamental aspects of vortex behaviour in the prototype problem for tropical cyclone intensification. After rapidly intensifying to a mature phase in which the maximum tangential wind speed remains quasi‐steady for a few days, the vortex ultimately decays. In a 20‐day simulation, the vortex never becomes globally steady. In particular, the upper anticyclone continues to expand for the duration of the integration. These results are consistent with those of recent studies using more sophisticated numerical models. As in the latter models, an important feature of the dynamics of spin‐up is the development of supergradient winds in the boundary layer and the vertical advection of the associated high tangential‐momentum air from the boundary layer to spin up the eyewall region. This mechanism, while consistent with some recently reported results, is not part of the classical theory of spin‐up.
On the sizes and lifetimes of cold pools
Authors: Romps David M. , Jeevanjee Nadir
Published: January 2016

Cold pools of air, which are formed by evaporating precipitation, play a critical role in the triggering of new precipitation. Despite their recognized importance, little effort has been devoted to building simple models of their dynamics. Here, analytical equations are derived for the radius, height, and buoyancy of a cylindrical cold pool as a function of time, and a scale analysis reveals that entrainment is a dominant influence. These governing equations yield simple expressions for the maximum sizes and lifetimes of cold pools. The terminal radius of a cold pool is relatively insensitive to its initial conditions, with a typical maximum radius of about 14 times the initial radius, give or take a factor of 2. The terminal time of a cold pool, on the other hand, can vary over orders of magnitude depending on its initial potential and kinetic energies. These predictions are validated against large‐eddy simulations.
Modeling the limited degree of starch gelatinization
Authors: Pérez‐Santos Diana‐Maricruz , Velazquez Gonzalo , Canonico‐Franco Marcia , Morales‐Sanchez Eduardo , Gaytan‐Martínez Marcela , Yañez‐Limon Jose‐Martin , Herrera‐Gomez Alberto
Published: January 2016

The kinetics of starch gelatinization is usually described as a first‐order reaction, that is, the rate of formation of gelatinized mass is assumed to be proportional to the unreacted amount. It is also assumed that the proportional constant, the reaction rate (k), has an Arrhenius‐type dependence on temperature. The equation derived from this model predicts that all the starch eventually gelatinizes at any given temperature for any k different from zero. However, it is well known that gelatinization only initiates above the so called “gelatinization temperature.” In this study it is employed an alternative model that properly describes the actual experimental behavior, which deviates considerably from the first‐order model prediction. The model introduces an empirical parameter that quantifies the extent of gelatinization when a starch‐water mixture is held at certain temperature for “long enough.” The gelatinization degree was evaluated by applying thermal treatments to 70% moisture‐content samples for 0, 0.5, 1, 3, 5, 7, and 10 min at several temperatures (61, 63, 65, 67, and 69°C). The gelatinization activation energy (EA) derived from the alternative model is 176 ± 10 kJ/mol. Since the proposed model closely reproduces the experimental behavior, it is suggested that this value better describes the actual process. The proposed model allows for the proper modeling of the starch‐gelatinization kinetics, which is relevant in starch gelatinization studies and in food processing industry.
A Synthetic Polymer Scaffold Reveals the Self-Maintenance Strategies of Rat Glioma Stem Cells by Organization of the Advantageous Niche
Authors: Tabu Kouichi , Muramatsu Nozomi , Mangani Christian , Wu Mei , Zhang Rong , Kimura Taichi , Terashima Kazuo , Bizen Norihisa , Kimura Ryosuke , Wang Wenqian , Murota Yoshitaka , Kokubu Yasuhiro , Nobuhisa Ikuo , Kagawa Tetsushi , Kitabayashi Issay , Bradley Mark , Taga Tetsuya
Published: January 2016

Cancer stem cells (CSCs) are believed to be maintained within a microenvironmental niche. Here we used polymer microarrays for the rapid and efficient identification of glioma CSC (GSC) niche mimicries and identified a urethane-based synthetic polymer, upon which two groups of niche components, namely extracellular matrices (ECMs) and iron are revealed. In cultures, side population (SP) cells, defined as GSCs in the rat C6 glioma cell line, are more efficiently sustained in the presence of their differentiated progenies expressing higher levels of ECMs and transferrin, while in xenografts, ECMs are supplied by the vascular endothelial cells (VECs), including SP cell-derived ones with distinctively greater ability to retain xenobiotics than host VECs. Iron is stored in tumor infiltrating host macrophages (Mφs), whose protumoral activity is potently enhanced by SP cell-secreted soluble factor(s). Finally, coexpression of ECM-, iron-, and Mφ-related genes is found to be predictive of glioma patients' outcome. Our polymer-based approach reveals the intrinsic capacities of GSCs, to adapt the environment to organize a self-advantageous microenvironment niche, for their maintenance and expansion, which redefines the current concept of anti-CSC niche therapy and has the potential to accelerate cancer therapy development.
BPA‐toxicity via superoxide anion overload and a deficit in β‐catenin signaling in human bone mesenchymal stem cells
Authors: Leem Yea‐Hyun , Oh Seikwan , Kang Hong‐Je , Kim Jung‐Hwa , Yoon Juno , Chang Jae‐Suk
Published: January 2016

Bisphenol A (BPA), used in the manufacture of products based on polycarbonate plastics and epoxy resins, is well known as an endocrine‐disrupting monomer. In the current study, BPA increased cytotoxicity in hBMSCs in a dose‐ and time‐dependent manner, concomitantly with increased lipid peroxidation. Increased cell death in BPA‐treated cells was markedly blocked by pretreatment with the superoxide dismutase mimetic MnTBAP and MnTMPyP, but not by catalase, glutathione, the glutathione peroxidase mimetic ebselen, the NOS inhibitor NAME, or the xanthine oxidase inhibitor allopurinol. Furthermore, the decline in nuclear β‐catenin and cyclin D1 levels in hBMSCs exposed to BPA was reversed by MnTBAP treatment. Finally, treatment of hBMSCs with the GSK3β inhibitor LiCl2 increased nuclear β‐catenin levels and significantly attenuated cytotoxicity compared with BPA treatment. Our current results in hBMSCs exposed to BPA suggest that BPA causes a disturbance in β‐catenin signaling via a superoxide anion overload. © 2016 The Authors Environmental Toxicology Published by Wiley Periodicals, Inc. Environ Toxicol 32: 344–352, 2017.
RNA‐binding protein hnRNPLL as a critical regulator of lymphocyte homeostasis and differentiation
Authors: Chang Xing
Published: January 2016

RNA‐binding proteins orchestrate posttranscriptional regulation of gene expression, such as messenger RNA (mRNA) splicing, RNA stability regulation, and translation regulation. Heterogeneous nuclear RNA‐binding proteins (hnRNPs) refer to a collection of unrelated RNA‐binding proteins predominantly located in the nucleus (Han et al. Biochem J 2010, 430:379–392). Although canonical functions of hnRNPs are to promote pre‐mRNA splicing, they are involved in all the processes of RNA metabolism through recognizing specific cis‐elements on RNA (Dreyfuss et al. Annu Rev Biochem 1993, 62:289–321; Huelga et al. Cell Rep 2012, 1:167–178; Krecic and Swanson. Curr Opin Cell Biol 1999, 11:363–371). Heterogeneous nuclear RNA‐binding protein L like (hnRNPLL) is a tissue‐specific hnRNP, which was identified as a regulator of CD45RA to CD45RO switching during memory T‐cell development (Oberdoerffer et al. Science 2008, 321:686–691; Topp et al. RNA 2008, 14:2038–2049; Wu et al. Immunity 2008, 29:863–875). Since then, hnRNPLL has emerged as a critical regulator of lymphocyte homeostasis and terminal differentiation, controlling alternative splicing or expression of critical genes for the lymphocytes development (Wu et al. Immunity 2008, 29:863–875; Chang et al. Proc Natl Acad Sci USA 2015, 112:E1888–E1897). This review will summarize recent advances in understanding the functions of hnRNPLL, focusing on its biochemical functions and physiological roles in lymphocyte differentiation and homeostasis. WIREs RNA 2016, 7:295–302. doi: 10.1002/wrna.1335

This article is categorized under:

RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications

RNA in Disease and Development > RNA in Development
Synthesis, Structures, Magnetic and Luminescent Properties of a Series of Iron(II) and Zinc(II) Coordination Frameworks with Versatile 4‐Substitued 1, 2,4‐Triazole Ligands
Authors: Zhai Bin , Li Zhong‐Yi , Zhang Xiang‐Fei , Wu Xiang‐Xia , Guo Jian‐Hua , Huo Jian‐Zhong , Ding Bin
Published: January 2016

Three multi‐dentate 1, 2,4‐triazole derivative ligands containing different 4‐substituted groups, namely N‐1, 2,4‐triazol‐4‐yl(pyridin‐3‐yl)methylenimine (L1), N‐1, 2,4‐triazol‐ 4‐yl(pyridin‐4‐yl)methylenimine (L2), and 4‐(2‐pyridine)‐1, 2,4‐triazole (L3) were used to isolate five iron(II) and zinc(II) coordination frameworks, [Zn(μ2‐L1)Cl2] (1), [Zn(μ2‐L2)Br2] (2), [Fe(L1)2(NCS)2(H2O)2] (3), [Fe(L3)2(dca)2(H2O)2] (4), and [Fe(L3)2(μ2‐dca)] (5) (dca = dicyanamide anion). When different zinc(II) salts were used to react with L1 and L2 under solvothermal conditions, two one‐dimensional (1D) zinc(II) coordination frameworks 1 and 2 containing four‐coordinate central zinc(II) atoms were isolated. 1 is a 3D achiral supra‐molecular framework, whereas 2 is a 3D chiral supra‐molecular framework containing helical chains on a 21 axis. 3 is a mono‐nuclear iron(II) coordination framework containing six‐coordinate central FeII atoms. When L3 was employed, mono‐nuclear iron(II) framework 4 and 1D iron(II) chain 5 could be isolated when different amounts of Nadca were introduced into the reaction system. Variable‐temperature magnetic susceptibility data of 3–5 were recorded in the 2–300 K temperature range indicating weak anti‐ferromagnetic interactions. The solid‐state luminescent properties of coordination polymers 1 and 2 were also investigated at room temperature.
Fundamental solution and the weight functions of the transient problem on a semi‐infinite crack propagating in a half‐plane
Authors: Antipov Y. A. , Smirnov A. V.
Published: January 2016

The two‐dimensional transient problem that is studied concerns a semi‐infinite crack in an isotropic solid comprising an infinite strip and a half‐plane joined together and having the same elastic constants. The crack propagates along the interface at constant speed subject to time‐independent loading. By means of the Laplace and Fourier transforms the problem is formulated as a vector Riemann‐Hilbert problem. When the distance from the crack to the boundary grows to infinity the problem admits a closed‐form solution. In the general case, a method of partial matrix factorization is proposed. In addition to factorizing some scalar functions it requires solving a certain system of integral equations whose numerical solution is computed by the collocation method. The stress intensity factors and the associated weight functions are derived. Numerical results for the weight functions are reported and the boundary effects are discussed. The weight functions are employed to describe propagation of a semi‐infinite crack beneath the half‐plane boundary at piecewise constant speed.
EDISON-WMW: Exact Dynamic Programing Solution of the Wilcoxon–Mann–Whitney Test
Authors: Marx Alexander , Backes Christina , Meese Eckart , Lenhof Hans-Peter , Keller Andreas
Published: January 2016

In many research disciplines, hypothesis tests are applied to evaluate whether findings are statistically significant or could be explained by chance. The Wilcoxon–Mann–Whitney (WMW) test is among the most popular hypothesis tests in medicine and life science to analyze if two groups of samples are equally distributed. This nonparametric statistical homogeneity test is commonly applied in molecular diagnosis. Generally, the solution of the WMW test takes a high combinatorial effort for large sample cohorts containing a significant number of ties. Hence, P value is frequently approximated by a normal distribution. We developed EDISON-WMW, a new approach to calculate the exact permutation of the two-tailed unpaired WMW test without any corrections required and allowing for ties. The method relies on dynamic programing to solve the combinatorial problem of the WMW test efficiently. Beyond a straightforward implementation of the algorithm, we presented different optimization strategies and developed a parallel solution. Using our program, the exact P value for large cohorts containing more than 1000 samples with ties can be calculated within minutes. We demonstrate the performance of this novel approach on randomly-generated data, benchmark it against 13 other commonly-applied approaches and moreover evaluate molecular biomarkers for lung carcinoma and chronic obstructive pulmonary disease (COPD). We found that approximated P values were generally higher than the exact solution provided by EDISON-WMW. Importantly, the algorithm can also be applied to high-throughput omics datasets, where hundreds or thousands of features are included. To provide easy access to the multi-threaded version of EDISON-WMW, a web-based solution of our algorithm is freely available at http://www.ccb.uni-saarland.de/software/wtest/.
Embedding EfS in Teacher Education Through a Multi-Level Systems Approach: Lessons From Queensland
Authors: Evans Neus (Snowy) , Ferreira Jo-Anne , Davis Julie , Stevenson Robert B.
Published: January 2016

This article reports on the fourth stage of an evolving study to develop a systems model for embedding education for sustainability (EfS) into preservice teacher education. The fourth stage trialled the extension of the model to a comprehensive state-wide systems approach involving representatives from all eight Queensland teacher education institutions and other key policy agencies and professional associations. Support for trialling the model included regular meetings among the participating representatives and an implementation guide. This article describes the first three stages of developing and trialling the model before presenting the case study and action research methods employed, four key lessons learned from the project, and the implications of the major outcomes for teacher education policies and practices. The Queensland-wide, multi-site case study revealed processes and strategies that can enable institutional change agents to engage productively in building capacity for embedding EfS at the individual, institutional, and state levels in preservice teacher education. Collectively, the project components provide a system-wide framework that offers strategies, examples, insights, and resources that can serve as a model for other states and/or territories wishing to implement EfS in a systematic and coherent fashion.
Intake of essential fatty acids in Indonesian children: secondary analysis of data from a nationally representative survey
Authors: Neufingerl Nicole , Djuwita Ratna , Otten-Hofman Anke , Nurdiani Reisi , Garczarek Ursula , Sulaeman Ahmad , Zock Peter L. , Eilander Ans
Published: January 2016

Essential fatty acids (EFA) such asα-linolenic acid (ALA) and linoleic acid (LA) are needed for healthy growth and development of children. Worldwide, reliable intake data of EFA are often lacking. The objective of this study was to investigate dietary intake of EFA in Indonesian children. Dietary intake data of 4–12-year-old children (n45 821) from a nationally representative Indonesian survey were used to estimate median intake and distribution of population fatty acid intake. Missing data on individual fatty acids in the Indonesian food composition table were complemented through chemical analyses of national representative food samples and imputation of data from the US nutrient database. Nutrient adequacy ratios were calculated as a percentage of FAO/WHO intake recommendations. The medians of total fat intake of the children was 26·7 (10th–90th percentile 11·2–40·0) percentage of total daily energy (%E). Intakes of fatty acids were 4·05 (10th–90th percentile 1·83–7·22) %E for total PUFA, 3·36 (10th–90th percentile 1·14–6·29) %E for LA and 0·20 (10th–90th percentile 0·07–0·66) %E for ALA. Median intake of PUFA was 67 % and that of ALA 40 % of the minimum amounts recommended by FAO/WHO. These data indicate that a majority of Indonesian children has intakes of PUFA and specifically ALA that are lower than recommended intake levels. Total fat and LA intakes may be suboptimal for a smaller yet considerable proportion of children. Public health initiatives should provide practical guidelines to promote consumption of PUFA-rich foods.
RETHINKING THE ORIGINS OF THE BRITISH PRISONS ACT OF 1835: IRELAND AND THE DEVELOPMENT OF CENTRAL-GOVERNMENT PRISON INSPECTION, 1820–1835
Authors: BUTLER RICHARD J.
Published: January 2016

While the introduction of central-government inspectors for prisons in a British act of 1835 has been seen as a key Whig achievement of the 1830s, the Irish precedent enacted by Charles Grant, a liberal Tory chief secretary, in the early 1820s, has gone unnoticed by scholars. The article sets out to trace the Irish prefiguring of this measure and, in the process, to consider prison reform in the United Kingdom in the early nineteenth century in a more transnational manner. A new analysis of the critical years between 1823 and 1835 in both Britain and Ireland based on a detailed examination of parliamentary inquiries and legislation shows how developments in the two countries overlapped and how reforms in one jurisdiction affected the other. This article explores the channels through which this exchange of knowledge and ideas occurred – both in parliament and through interlinked penal-reform philanthropic societies in both countries. This article also highlights inadequacies with the theory supported by some scholars that Ireland functioned as a laboratory for British social reform at this time, and instead suggests a more fluid exchange of ideas in both directions at different times.
Interactions between mefloquine and the anti-fibrotic drug silymarin onSchistosoma mansoniinfections in mice
Authors: Kamel Reem O.A.
Published: January 2016

The present study tests the anti-inflammatory and anti-fibrotic effects of silymarin alone or combined with mefloquine on acute schistosomiasis by evaluating parasitological, histopathological, biochemical and immunological parameters. Male CDI Swiss mice were divided into seven groups, which included healthy controls, mice infected withSchistosoma mansonior treated with silymarin (140 mg/kg body weight) or mefloquine (400 mg/kg body weight), or mice treated with a combination of both drugs and uninfected mice simply treated with mefloquine or silymarin alone. All mouse groups were sacrificed 8 weeks post-infection (pi) and/or post-treatment. Those infected mice treated with both silymarin and mefloquine showed a significant decrease (P<  0.001) in worm burden, immunoglobulins (IgG and IgM), liver function enzymes and granuloma diameter, with complete eradication of immature and mature eggs. In conclusion, treatment with silymarin combined with mefloquine in murine schistosomiasis was able to reduce granulomatous reactions and hepatic fibrosis. Hence, this combination is a new strategy to be studied as an efficient tool in the treatment of schistosomal liver fibrosis.
Gender Statistics and Local Governance in China: State Feminist versus Feminist Political Economy Approaches
Authors: Chen Lanyan
Published: January 2016

Gender statistics provide an essential tool to mainstream gender equality in policymaking through the recognition by government and the public of gender differences in all walks of life. One legacy of feminist movements since the 1990s has been a focus on the challenges women face to effect substantive equality with men. Based on the findings of a project carried out in three districts of Tianjin, this paper identifies a lack of gender statistics in China's statistical system and the resulting negative impacts on local policymaking. The findings point to weaknesses in the Chinese “state feminist” approach to gender statistics, mostly at the level of the central government. From a feminist political economy perspective, the paper argues, policymaking in China is a process built upon centralized statistical reporting systems that serve the senior governments more than local communities. Gender statistics have the potential to enhance local governance in China when policymaking becomes a site of contestation where community activists demand the use of statistics to assist policies that promote equality.
How Socialization Shapes Chinese Views of America and the World
Authors: GRIES PETER HAYS , SANDERS MATTHEW
Published: January 2016

Urban Chinese today do not appear to trust foreign countries. Why are they so suspicious? Over the past quarter century, the Chinese Communist Party (CCP) has utilized its educational and propaganda systems to produce historical narratives of imperial China's beneficence towards its East Asian neighbors, and of an early modern ‘Century of Humiliation’ at the hands of ‘imperialist’ foreign powers. Qualitative analysis of Chinese social media today suggests that these narratives are tied to widespread popular distrust of China's ‘ungrateful’ East Asian neighbors and the ‘hegemonic’ West today. Interrogating a 2012 survey of urban Chinese, this paper explores the sources of international attitudes quantitatively. It first examines whether Chinese today do indeed distrust foreign countries. It then tests two hypotheses about the drivers of Chinese distrust towards the world today. A ‘top-down’ socialization hypothesis holds that political (e.g. party propaganda via education and the media) and/or social (e.g. peer groups, social conformity) pressures shape the international attitudes of the Chinese people. A ‘bottom-up’ psychological hypothesis, by contrast, holds that individual differences like age and gender shape Chinese attitudes. We find substantial support for the former: more years of education are associated with levels of dis/trust in foreign countries in the socially or politically appropriate ways. However, we also find that ‘bottom-up’ individual differences in subjective interest in international affairs interact with ‘top-down’ socialization processes like education and media exposure in shaping the international attitudes of urban Chinese today. The prevalence of public discourses of distrust towards foreign countries does not bode well for Chinese foreign policy in the twenty-first century.
A Failure in ‘Designed Citizenship’: A Case Study in a Minority-Han Merger School in Xinjiang Uyghur Autonomous Region
Authors: YI LIN
Published: January 2016

Drawing upon the theses of State racism (Michel Foucault), homo sacer (Giorgio Agamben), and safe citizenship (Cynthia Weber), and fieldwork data collected from a multiethnic primary school in Xinjiang, this paper examines the way in which the state agencies of the local government, the school and mainstream citizens design citizenship for Uyghurs, and how Uyghurs interpret and act upon their citizenship. The findings show why, and how, designed citizenship by the mainstream system for Uyghurs has failed to produce a desirably productive force for the prosperity of both the Uyghur community and society at large. The findings require re-consideration of what could be a win-win citizenship for both the state and the citizen.
Social Network Model of Political Participation in Japan*
Authors: LEE AIE-RIE
Published: January 2016

The objective of the study is to re-examine the Verba, Nie, and Kim (VNK)'s path-breaking analysis of political participation and political equality, under the inclusion of a social network model in Japan. In particular, the present research investigates how and why we find the extremely low correlations between one's socio-economic resource level (SERL) and political participation in Japan, the evidence unsatisfactorily explained by the VNK analysis. Building on the social network model and employing the first wave of the Asian Barometer survey conducted in 2003, this research presents a more comprehensive model of political participation. The study finds three major kinds of causes for the weak associations between SERL–participation levels in Japan: exogenous factors (i.e., sex, urbanization, and age); equalizing impact of social networks; and weak SERL–psychological involvement linkage. From the viewpoint of the social network model, it is clear that the weak SERL–participation linkage is derived from the equalizing impact of group-based processes, yet uniquely Japanese style of network involvement.
Oil, Coal Industry Leaders Fault Obama Policies at Energy Forum
Authors: Showstack Randy
Published: January 2016

In a review of the energy industry, fossil fuel industry leaders said they are fighting federal policies. The solar industry recently benefited from a 5-year tax credit.
New insights into the phenotype of human dendritic cell populations
Authors: Clark Georgina Jane , Kupresanin Fiona , Fromm Phillip Dieter , Ju Xinsheng , Muusers Leticia , Silveira Pablo Alejandro , Elgundi Zehra , Gasiorowski Robin Edward , Papadimitrious Michael Stefan , Bryant Christian , Lee Kenneth Maan Liong , Clarke Candice Jane , Young James William , Chan Andrew , Harman Andrew , Botting Rachel , Cabezón Raquel , Benitez‐Ribas Daniel , Brooks Anna Elizabeth Stella , Dunbar Phillip Rodney , Hart Derek Nigel John
Published: January 2016

HLDA10 is the Tenth Human Leukocyte Differentiation Antigen (HLDA) Workshop. The HLDA Workshops provide a mechanism to allocate cluster of differentiation (CD) nomenclature by engaging in interlaboratory studies. As the host laboratory, we invited researchers from national and international academic and commercial institutions to submit monoclonal antibodies (mAbs) to human leukocyte surface membrane molecules, particularly those that recognised molecules on human myeloid cell populations and dendritic cells (DCs). These mAbs were tested for activity and then distributed as a blinded panel to 15 international laboratories to test on different leukocyte populations. These populations included blood DCs, skin‐derived DCs, tonsil leukocytes, monocyte‐derived DCs, CD34‐derived DCs, macrophage populations and diagnostic acute myeloid leukaemia and lymphoma samples. Each laboratory was provided with enough mAb to perform five repeat experiments. Here, we summarise the reactivity of different mAb to 68 different cell‐surface molecules expressed by human myeloid and DC populations. Submitted mAbs to some of the molecules were further validated to collate data required to designate a formal CD number. This collaborative process provides the broader scientific community with an invaluable data set validating mAbs to leukocyte‐surface molecules.
Nucleophilic arylation with tetraarylphosphonium salts
Authors: Deng Zuyong , Lin Jin-Hong , Xiao Ji-Chang
Published: January 2016

Organic phosphonium salts have served as important intermediates in synthetic chemistry. But the use of a substituent on the positive phosphorus as a nucleophile to construct C–C bond remains a significant challenge. Here we report an efficient transition-metal-free protocol for the direct nucleophilic arylation of carbonyls and imines with tetraarylphosphonium salts in the presence of caesium carbonate. The aryl nucleophile generated from phosphonium salt shows low basicity and good nucleophilicity, as evidenced by the successful conversion of enolizable aldehydes and ketones. The reaction is not particularly sensitive to water, shows wide substrate scope, and is compatible with a variety of functional groups including cyano and ester groups. Compared with the arylmetallic reagents that are usually moisture sensitive, the phosphonium salts are shelf-stable and can be easily handled.
Human predation contributed to the extinction of the Australian megafaunal bird Genyornis newtoni ∼47 ka
Authors: Miller Gifford , Magee John , Smith Mike , Spooner Nigel , Baynes Alexander , Lehman Scott , Fogel Marilyn , Johnston Harvey , Williams Doug , Clark Peter , Florian Christopher , Holst Richard , DeVogel Stephen
Published: January 2016

Although the temporal overlap between human dispersal across Australia and the disappearance of its largest animals is well established, the lack of unambiguous evidence for human–megafauna interactions has led some to question a human role in megafaunal extinction. Here we show that diagnostic burn patterns on eggshell fragments of the megafaunal bird Genyornis newtoni, found at >200 sites across Australia, were created by humans discarding eggshell in and around transient fires, presumably made to cook the eggs. Dating by three methods restricts their occurrence to between 53.9 and 43.4 ka, and likely before 47 ka. Dromaius (emu) eggshell occur frequently in deposits from >100 ka to present; burnt Dromaius eggshell first appear in deposits the same age as those with burnt Genyornis eggshell, and then continually to modern time. Harvesting of their eggs by humans would have decreased Genyornis reproductive success, contributing to the bird’s extinction by ∼47 ka.
Inactivation of nuclear GSK3β by Ser389 phosphorylation promotes lymphocyte fitness during DNA double-strand break response
Authors: Thornton Tina M. , Delgado Pilar , Chen Liang , Salas Beatriz , Krementsov Dimitry , Fernandez Miriam , Vernia Santiago , Davis Roger J. , Heimann Ruth , Teuscher Cory , Krangel Michael S. , Ramiro Almudena R. , Rincón Mercedes
Published: January 2016

Variable, diversity and joining (V(D)J) recombination and immunoglobulin class switch recombination (CSR) are key processes in adaptive immune responses that naturally generate DNA double-strand breaks (DSBs) and trigger a DNA repair response. It is unclear whether this response is associated with distinct survival signals that protect T and B cells. Glycogen synthase kinase 3β (GSK3β) is a constitutively active kinase known to promote cell death. Here we show that phosphorylation of GSK3β on Ser389 by p38 MAPK (mitogen-activated protein kinase) is induced selectively by DSBs through ATM (ataxia telangiectasia mutated) as a unique mechanism to attenuate the activity of nuclear GSK3β and promote survival of cells undergoing DSBs. Inability to inactivate GSK3β through Ser389 phosphorylation in Ser389Ala knockin mice causes a decrease in the fitness of cells undergoing V(D)J recombination and CSR. Preselection-Tcrβ repertoire is impaired and antigen-specific IgG antibody responses following immunization are blunted in Ser389GSK3β knockin mice. Thus, GSK3β emerges as an important modulator of the adaptive immune response.
Interplay between type IV pili activity and exopolysaccharides secretion controls motility patterns in single cells of Myxococcus xanthus
Authors: Hu Wei , Gibiansky Maxsim L. , Wang Jing , Wang Chuandong , Lux Renate , Li Yuezhong , Wong Gerard C. L. , Shi Wenyuan
Published: January 2016

Myxococcus xanthus performs coordinated social motility of cell groups through the extension and retraction of type IV pili (TFP) on solid surfaces, which requires both TFP and exopolysaccharides (EPS). By submerging cells in a liquid medium containing 1% methylcellulose, M. xanthus TFP-driven motility was induced in isolated cells and independently of EPS. We measured and analyzed the movements of cells using community tracking algorithms, which combine single-cell resolution with statistics from large sample populations. Cells without significant multi-cellular social interactions have surprisingly complex behaviors: EPS− cells exhibited a pronounced increase in the tendency to stand vertically and moved with qualitatively different characteristics than other cells. A decrease in the EPS secretion of cells correlates with a higher instantaneous velocity, but with lower directional persistence in trajectories. Moreover, EPS− cells do not adhere to the surface as strongly as wild-type and EPS overproducing cells and display a greater tendency to have large deviations between the direction of movement and the cell axis, with cell velocity showing only minimal dependence on the direction of movement. The emerging picture is that EPS does not simply provide rheological resistance to a single mechanism but rather that the availability of EPS impacts motility pattern.
The β2 clamp in the Mycobacterium tuberculosis DNA polymerase III αβ2ε replicase promotes polymerization and reduces exonuclease activity
Authors: Gu Shoujin , Li Wenjuan , Zhang Hongtai , Fleming Joy , Yang Weiqiang , Wang Shihua , Wei Wenjing , Zhou Jie , Zhu Guofeng , Deng Jiaoyu , Hou Jian , Zhou Ying , Lin Shiqiang , Zhang Xian-En , Bi Lijun
Published: January 2016

DNA polymerase III (DNA pol III) is a multi-subunit replication machine responsible for the accurate and rapid replication of bacterial genomes, however, how it functions in Mycobacterium tuberculosis (Mtb) requires further investigation. We have reconstituted the leading-strand replication process of the Mtb DNA pol III holoenzyme in vitro and investigated the physical and functional relationships between its key components. We verify the presence of an αβ2ε polymerase-clamp-exonuclease replicase complex by biochemical methods and protein-protein interaction assays in vitro and in vivo and confirm that, in addition to the polymerase activity of its α subunit, Mtb DNA pol III has two potential proofreading subunits; the α and ε subunits. During DNA replication, the presence of the β2 clamp strongly promotes the polymerization of the αβ2ε replicase and reduces its exonuclease activity. Our work provides a foundation for further research on the mechanism by which the replication machinery switches between replication and proofreading and provides an experimental platform for the selection of antimicrobials targeting DNA replication in Mtb.
Constructal approach to cell membranes transport: Amending the ‘Norton-Simon’ hypothesis for cancer treatment
Authors: Lucia Umberto , Ponzetto Antonio , Deisboeck Thomas S.
Published: January 2016

To investigate biosystems, we propose a new thermodynamic concept that analyses ion, mass and energy flows across the cell membrane. This paradigm-shifting approach has a wide applicability to medically relevant topics including advancing cancer treatment. To support this claim, we revisit ‘Norton-Simon’ and evolving it from an already important anti-cancer hypothesis to a thermodynamic theorem in medicine. We confirm that an increase in proliferation and a reduction in apoptosis trigger a maximum of ATP consumption by the tumor cell. Moreover, we find that positive, membrane-crossing ions lead to a decrease in the energy used by the tumor, supporting the notion of their growth inhibitory effect while negative ions apparently increase the cancer’s consumption of energy hence reflecting a growth promoting impact. Our results not only represent a thermodynamic proof of the original Norton-Simon hypothesis but, more concretely, they also advance the clinically intriguing and experimentally testable, diagnostic hypothesis that observing an increase in negative ions inside a cellin vitroand inside a diseased tissuein vivo, may indicate growth or recurrence of a tumor. We conclude with providing theoretical evidence that applying electromagnetic field therapy early on in the treatment cycle may maximize its anti-cancer efficacy.
Integrated optofluidic-microfluidic twin channels: toward diverse application of lab-on-a-chip systems
Authors: Lv Chao , Xia Hong , Guan Wei , Sun Yun-Lu , Tian Zhen-Nan , Jiang Tong , Wang Ying-Shuai , Zhang Yong-Lai , Chen Qi-Dai , Ariga Katsuhiko , Yu Yu-De , Sun Hong-Bo
Published: January 2016

Optofluidics, which integrates microfluidics and micro-optical components, is crucial for optical sensing, fluorescence analysis and cell detection. However, the realization of an integrated system from optofluidic manipulation and a microfluidic channel is often hampered by the lack of a universal substrate for achieving monolithic integration. In this study, we report on an integrated optofluidic-microfluidic twin channels chip fabricated by one-time exposure photolithography, in which the twin microchannels on both surfaces of the substrate were exactly aligned in the vertical direction. The twin microchannels can be controlled independently, meaning that fluids could flow through both microchannels simultaneously without interfering with each other. As representative examples, a tunable hydrogel microlens was integrated into the optofluidic channel by femtosecond laser direct writing, which responds to the salt solution concentration and could be used to detect the microstructure at different depths. The integration of such optofluidic and microfluidic channels provides an opportunity to apply optofluidic detection practically and may lead to great promise for the integration and miniaturization of Lab-on-a-Chip systems.
Large-Area Growth of Turbostratic Graphene on Ni(111) via Physical Vapor Deposition
Authors: Garlow Joseph A. , Barrett Lawrence K. , Wu Lijun , Kisslinger Kim , Zhu Yimei , Pulecio Javier F.
Published: January 2016

Single-layer graphene has demonstrated remarkable electronic properties that are strongly influenced by interfacial bonding and break down for the lowest energy configuration of stacked graphene layers (AB Bernal). Multilayer graphene with relative rotations between carbon layers, known as turbostratic graphene, can effectively decouple the electronic states of adjacent layers, preserving properties similar to that of SLG. While the growth of AB Bernal graphene through chemical vapor deposition has been widely reported, we investigate the growth of turbostratic graphene on heteroepitaxial Ni(111) thin films utilizing physical vapor deposition. By varying the carbon deposition temperature between 800 –1100 °C, we report an increase in the graphene quality concomitant with a transition in the size of uniform thickness graphene, ranging from nanocrystallites to thousands of square microns. Combination Raman modes of as-grown graphene within the frequency range of 1650 cm−1 to 2300 cm−1, along with features of the Raman 2D mode, were employed as signatures of turbostratic graphene. Bilayer and multilayer graphene were directly identified from areas that exhibited Raman characteristics of turbostratic graphene using high-resolution TEM imaging. Raman maps of the pertinent modes reveal large regions of turbostratic graphene on Ni(111) thin films at a deposition temperature of 1100 °C.
Towards a novel bioelectrocatalytic platform based on “wiring” of pyrroloquinoline quinone-dependent glucose dehydrogenase with an electrospun conductive polymeric fiber architecture
Authors: Gladisch Johannes , Sarauli David , Schäfer Daniel , Dietzel Birgit , Schulz Burkhard , Lisdat Fred
Published: January 2016

Electrospinning is known as a fabrication technique for electrode architectures that serve as immobilization matrices for biomolecules. The current work demonstrates a novel approach to construct a conductive polymeric platform, capable not only of immobilization, but also of electrical connection of the biomolecule with the electrode. It is produced upon electrospinning from mixtures of three different highly conductive sulfonated polyanilines and polyacrylonitrile on ITO electrodes. The resulting fiber mats are with a well-retained conductivity. After coupling the enzyme pyrroloquinoline quinone-dependent glucose dehydrogenase (PQQ-GDH) to polymeric structures and addition of the substrate glucose an efficient bioelectrocatalysis is demonstrated. Depending on the choice of the sulfonated polyanilline mediatorless bioelectrocatalysis starts at low potentials; no large overpotential is needed to drive the reaction. Thus, the electrospun conductive immobilization matrix acts here as a transducing element, representing a promising strategy to use 3D polymeric scaffolds as wiring agents for active enzymes. In addition, the mild and well reproducible fabrication process and the active role of the polymer film in withdrawing electrons from the reduced PQQ-GDH lead to a system with high stability. This could provide access to a larger group of enzymes for bioelectrochemical applications including biosensors and biofuel cells.
The aberrantly expressed miR-193b-3p contributes to preeclampsia through regulating transforming growth factor-β signaling
Authors: Zhou Xinyao , Li Qiaoli , Xu Jiawei , Zhang Xiaojing , Zhang Huijuan , Xiang Yuqian , Fang Chuantao , Wang Teng , Xia Shihui , Zhang Qiang , Xing Qinghe , He Lin , Wang Lei , Xu Mingqing , Zhao Xinzhi
Published: January 2016

Preeclampsia (PE) is a leading cause of maternal mortality worldwide. Several studies have detected some differentially expressed microRNAs in the preeclamptic placenta, but few of the identified microRNAs demonstrated consistent findings among different research studies. In this study, high-throughput microRNA sequencing (HTS) of 9 preeclamptic and 9 normal placentas was performed. Seventeen microRNAs were identified to be up-regulated and 8 down-regulated in preeclamptic placentas. Eight differentially expressed microRNAs except one identified in our study were determined to be consistent with at least one previous study, while sixteen were newly found. We performed qRT-PCR with independent 22 preeclamptic placentas and 20 control placentas to verify the differentially expressed microRNAs and ten microRNAs were validated. The predicted target genes of the aberrantly expressed miR-193b-3p were enriched in the following gene ontology categories: cell motility and migration, cell proliferation and angiogenesis. We also found that miR-193b-3p significantly decreased the migration and invasion of trophoblast (HTR-8/SVneo) cells and that miR-193b-3p could regulate trophoblasts migration and invasion through binding onto the 3′UTR target site of TGF-β2. In conclusion, we identified a list of differentially expressed microRNAs in PE placentas by HTS and provided preliminary evidence for the role of miR-193b-3p in the pathogenesis of preeclampsia.
Structure of a variable lymphocyte receptor-like protein from the amphioxus Branchiostoma floridae
Authors: Cao Dong-Dong , Liao Xin , Cheng Wang , Jiang Yong-Liang , Wang Wen-Jie , Li Qiong , Chen Jun-Yuan , Chen Yuxing , Zhou Cong-Zhao
Published: January 2016

Discovery of variable lymphocyte receptors (VLRs) in agnathans (jawless fish) has brought the origin of adaptive immunity system (AIS) forward to 500 million years ago accompanying with the emergence of vertebrates. Previous findings indicated that amphioxus, a representative model organism of chordate, also possesses some homologs of the basic components of TCR/BCR-based AIS, but it remains unknown if there exist any components of VLR-based AIS in amphioxus. Bioinformatics analyses revealed the amphioxus Branchiostoma floridae encodes a group of putative VLR-like proteins. Here we reported the 1.79 Å crystal structure of Bf66946, which forms a crescent-shaped structure of five leucine-rich repeats (LRRs). Structural comparisons indicated that Bf66946 resembles the lamprey VLRC. Further electrostatic potential analyses showed a negatively-charged patch at the concave of LRR solenoid structure that might be responsible for antigen recognition. Site-directed mutagenesis combined with bacterial binding assays revealed that Bf66946 binds to the surface of Gram-positive bacteria Staphylococcus aureus and Streptococcus pneumonia via a couple of acidic residues at the concave. In addition, the closest homolog of Bf66946 is highly expressed in the potential immune organ gill of Branchiostoma belcheri. Altogether, our findings provide the first structural evidence for the emergence of VLR-like molecules in the basal chordates.
Spatially resolved and orientation dependent Raman mapping of epitaxial lateral overgrowth nonpolar a-plane GaN on r-plane sapphire
Authors: Jiang Teng , Xu Sheng-rui , Zhang Jin-cheng , Xie Yong , Hao Yue
Published: January 2016

Uncoalesced a-plane GaN epitaxial lateral overgrowth (ELO) structures have been synthesized along two mask stripe orientations on a-plane GaN template by MOCVD. The morphology of two ELO GaN structures is performed by Scanning electronic microscopy. The anisotropy of crystalline quality and stress are investigated by micro-Raman spectroscopy. According to the Raman mapping spectra, the variations on the intensity, peak shift and the full width at half maximum (FWHM) of GaN E2 (high) peak indicate that the crystalline quality improvement occurs in the window region of the GaN stripes along [0001], which is caused by the dislocations bending towards the sidewalls. Conversely, the wing regions have better quality with less stress as the dislocations propagated upwards when the GaN stripes are along ["Equation missing"]. Spatial cathodoluminescence mapping results further support the explanation for the different dislocation growth mechanisms in the ELO processes with two different mask stripe orientations.
Translation Microscopy (TRAM) for super-resolution imaging
Authors: Qiu Zhen , Wilson Rhodri S , Liu Yuewei , R Dun Alison , Saleeb Rebecca S , Liu Dongsheng , Rickman Colin , Frame Margaret , Duncan Rory R , Lu Weiping
Published: January 2016

Super-resolution microscopy is transforming our understanding of biology but accessibility is limited by its technical complexity, high costs and the requirement for bespoke sample preparation. We present a novel, simple and multi-color super-resolution microscopy technique, called translation microscopy (TRAM), in which a super-resolution image is restored from multiple diffraction-limited resolution observations using a conventional microscope whilst translating the sample in the image plane. TRAM can be implemented using any microscope, delivering up to 7-fold resolution improvement. We compare TRAM with other super-resolution imaging modalities, including gated stimulated emission deletion (gSTED) microscopy and atomic force microscopy (AFM). We further developed novel ‘ground-truth’ DNA origami nano-structures to characterize TRAM, as well as applying it to a multi-color dye-stained cellular sample to demonstrate its fidelity, ease of use and utility for cell biology.
Kallikrein-related peptidase 8 is expressed in myocardium and induces cardiac hypertrophy
Authors: Cao Buqing , Yu Qing , Zhao Wei , Tang Zhiping , Cong Binhai , Du Jiankui , Lu Jianqiang , Zhu Xiaoyan , Ni Xin
Published: January 2016

The tissue kallikrein-related peptidase family (KLK) is a group of trypsin- and chymotrypsin-like serine proteases that share a similar homology to parent tissue kallikrein (KLK1). KLK1 is identified in heart and has anti-hypertrophic effects. However, whether other KLK family members play a role in regulating cardiac function remains unknown. In the present study, we demonstrated for the first time that KLK8 was expressed in myocardium. KLK8 expression was upregulated in left ventricle of cardiac hypertrophy models. Both intra-cardiac adenovirus-mediated and transgenic-mediated KLK8 overexpression led to cardiac hypertrophy in vivo. In primary neonatal rat cardiomyocytes, KLK8 knockdown inhibited phenylephrine (PE)-induced cardiomyocyte hypertrophy, whereas KLK8 overexpression promoted cardiomyocyte hypertrophy via a serine protease activity-dependent but kinin receptor-independent pathway. KLK8 overexpression increased epidermal growth factor (EGF) production, which was blocked by the inhibitors of serine protease. EGF receptor (EGFR) antagonist and EGFR knockdown reversed the hypertrophy induced by KLK8 overexpression. KLK8-induced cardiomyocyte hypertrophy was also significantly decreased by blocking the protease-activated receptor 1 (PAR1) or PAR2 pathway. Our data suggest that KLK8 may promote cardiomyocyte hypertrophy through EGF signaling- and PARs-dependent but a kinin receptor-independent pathway. It is implied that different KLK family members can subtly regulate cardiac function and remodeling.