bluuebunny/crossref_metadata_2025 huggingface dataset:
Treed Avalanche Forecasting: Mitigating Avalanche Danger Utilizing Bayesian Additive Regression Trees
Authors: Blattenberger Gail , Fowles Richard
Published: April 2016

Little Cottonwood Canyon Highway is a dead‐end, two‐lane road leading to Utah's Alta and Snowbird ski resorts. It is the only road access to these resorts and is heavily traveled during the ski season. Professional avalanche forecasters monitor this road throughout the ski season in order to make road closure decisions in the face of avalanche danger. Forecasters at the Utah Department of Transportation (UDOT) avalanche guard station at Alta have maintained an extensive daily winter database on explanatory variables relating to avalanche prediction. Whether or not an avalanche crosses the road is modeled in this paper via Bayesian additive tree methods. Utilizing daily winter data from 1995 to 2011, results show that using Bayesian tree analysis outperforms traditional statistical methods in terms of realized misclassification costs that take into consideration asymmetric losses arising from two types of error. Closing the road when an avalanche does not occur is an error harmful to resort owners, and not closing the road when one does may result in injury or death. Copyright © 2016 John Wiley & Sons, Ltd.
Dihydrotestosterone treatment rescues the decline in protein synthesis as a result of sarcopenia in isolated mouse skeletal muscle fibres
Authors: Wendowski Oskar , Redshaw Zoe , Mutungi Gabriel
Published: April 2016

Background

Sarcopenia, the progressive decline in skeletal muscle mass and function with age, is a debilitating condition. It leads to inactivity, falls, and loss of independence. Despite this, its cause(s) and the underlying mechanism(s) are still poorly understood.

Methods

In this study, small skeletal muscle fibre bundles isolated from the extensor digitorum longus (a fast‐twitch muscle) and the soleus (a slow‐twitch muscle) of adult mice of different ages (range 100–900 days old) were used to investigate the effects of ageing and dihydrotestosterone (DHT) treatment on protein synthesis as well as the expression and function of two amino acid transporters; the sodium‐coupled neutral amino acid transporter (SNAT) 2, and the sodium‐independent L‐type amino‐acid transporter (LAT) 2.

Results

At all ages investigated, protein synthesis was always higher in the slow‐twitch than in the fast‐twitch muscle fibres and decreased with age in both fibre types. However, the decline was greater in the fast‐twitch than in the slow‐twitch fibres and was accompanied by a reduction in the expression of SNAT2 and LAT2 at the protein level. Again, the decrease in the expression of the amino acid transporters was greater in the fast‐twitch than in the slow‐twitch fibres. In contrast, ageing had no effect on SNAT2 and LAT2 expressions at the mRNA level. Treating the muscle fibre bundles with physiological concentrations (~2 nM) of DHT for 1 h completely reversed the effects of ageing on protein synthesis and the expression of SNAT2 and LAT2 protein in both fibre types.

Conclusion

From the observations that ageing is accompanied by a reduction in protein synthesis and transporter expression and that these effects are reversed by DHT treatment, we conclude that sarcopenia arises from an age‐dependent reduction in protein synthesis caused, in part, by the lack of or by the low bioavailability of the male sex steroid, DHT.
Peptide backbone modification in the bend region of amyloid‐β inhibits fibrillogenesis but not oligomer formation
Authors: Johnson Erik C. B. , Lanning Jennifer D. , Meredith Stephen C.
Published: April 2016

Current evidence suggests that oligomers of the amyloid‐β (Aβ) peptide are involved in the cellular toxicity of Alzheimer's disease, yet their biophysical characterization remains difficult because of lack of experimental control over the aggregation process under relevant physiologic conditions. Here, we show that modification of the Aβ peptide backbone at Gly29 allows for the formation of oligomers but inhibits fibril formation at physiologic temperature and pH. Our results suggest that the putative bend region in Aβ is important for higher‐order aggregate formation. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
Quest for the chemical synthesis of proteins
Authors: Engelhard Martin
Published: April 2016

The chemical synthesis of proteins has been the wish of chemists since the early 19th century. There were decisive methodological steps necessary to accomplish this aim. Cornerstones were the introduction of the Z‐protecting group of Bergmann and Zervas, the development of Solid‐phase Peptide Synthesis of Merrifield, and the establishment of Native Chemical Ligation by Kent. Chemical synthesis of proteins has now become generally applicable technique for the synthesis of proteins with tailor made properties which can be applied not only in vitro but also in vivo .Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
Reshaping Migrant Labour Market Geographies: Local Regularisations and the Informal Economy
Authors: Visser M. Anne
Published: April 2016

Regularisation remains a strategic site for studying the political economy of migrant socio‐economic incorporation. Research suggests that immigrant regularisation policies improve labour market opportunities for undocumented migrant workers in host societies – particularly those engaged in the informal economy. However, research on regularisation remains focused on national‐level policy efforts, despite increased political activity by sub‐national levels of government on immigration issues across migrant‐receiving societies. This article identifies and examines local migrant labour market regularisations – a new political geography of labour market regulation – and explores the potential of these policies to influence labour market mobility and opportunity for irregular migrants in the US. Using data on 5,528 policy ordinances across 3,067 city, counties, and states, implementation trends across four local migrant labour market regularisation policy domains were analysed for the time period 2001–2014. Case studies of local‐level government activism within each policy domain are also presented. Findings indicate that the implementation of local migrant labour market regularisations in the US has become increasingly unfavourable towards migrant workers and that within these new political geographies, local governments are emerging as central actors in shaping migrant labour market opportunities. The article concludes by reflecting on the implications these new political geographies present for the economic incorporation of irregular migrants and their role in constructing a new scalar reality of migrant labour market regulation. Copyright © 2016 John Wiley & Sons, Ltd.
A facile route to large‐scale synthesis MoO2 and MoO3 as electrode materials for high‐performance supercapacitors
Authors: Xuan H. C. , Zhang Y. Q. , Xu Y. K. , Li H. , Han P. D. , Wang D. H. , Du Y. W.
Published: April 2016

MoO3 and MoO2 materials have been successfully synthesized by thermal decomposition of ammonium paramolybdate in air and a sealed quartz tube, respectively. The microstructure of as‐synthesized MoO3 is composed of irregular lamellar plates with a plate thickness around 100 nm and MoO2 has the larger grain size with lamellar plates connected with each other. A maximum specific capacitance of 318 F/g at 0.5 A/g is obtained for MoO2 prepared in a closed environment. On the other hand, the sample MoO3 exhibits excellent rate capacity with specific capacitances of 218, 209, 196, 188, 176, and 160 F/g at current densities of 0.5, 1, 2, 3, 4, and 5 A/g, respectively. These results pave the way to consider MoO3 and MoO2 as prospective materials for energy‐storage applications.
Emerging blue‐UV luminescence in cerium doped YAG nanocrystals
Authors: Shirmane Liana , Pankratov Vladimir
Published: April 2016

Time‐resolved luminescence properties of Ce3+ doped Y3Al5O12 (YAG) nanocrystals have been studied by means of vacuum‐ultraviolet excitation spectroscopy. It was discovered that additionally to the regular Ce3+ yellow‐green emission which is well‐known luminescence in YAG, new emission covering a broad spectral range from 2.7 eV to 3.5 eV was revealed in the luminescence spectra for all YAG:Ce nanocrystals studied. This blue‐UV emission has fast decay time about 7 ns as well as intensive well‐resolved excitation band peaking at 5.9 eV and, in contrast to green Ce3+ emission, practically is not excited at higher energies. The origin of the blue‐UV emission is tentatively suggested and discussed. (© 2016 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)
Phase Behavior of Ascorbyl Palmitate Coagels Loaded with Oligonucleotides as a New Carrier for Vaccine Adjuvants
Authors: Ullio Gamboa Gabriela V. , Benedini Luciano A. , Schulz Pablo C. , Allemandi Daniel A.
Published: April 2016

In this work, the phase behavior variations of an ascorbyl palmitate (Asc16) system in aqueous solution were analyzed when immunologically active hydrophilic compounds (CpG and OVA) were introduced. This study was carried out through optical polarizing microscopy (OPM) and differential scanning calorimetry (DSC) at different temperatures and over a broad range of concentrations. The combination of both techniques allowed the determination of a complete phase diagram which was compared with those built for Asc16‐water system and it was demonstrated that fixed concentrations of hydrophilic compounds (300 and 24 µg/g for CpG‐ODN and OVA respectively) generate two lamellar liquid crystals, a cubic liquid crystal phase, and also other aggregates. However, no changes were observed in the phase diagram in terms of formation of new mesophases. The aqueous phase behavior was also studied as a function of surfactant and temperature. DSC and Fourier transform infrared spectroscopy (FT‐IR) measurements show differences in the free water and mainly in the secondary hydration layer, which confirm that the studied compounds are situated in the aqueous domain. The construction and analysis of Asc16 phase diagrams with a fixed concentration of CpG‐ODN/OVA allows the comprehension of Asc16 phase behavior and could be easily adapted to other concentrations. Moreover, these findings could be extrapolated to other hydrophilic substances in aqueous solution introduced in liquid crystal phases since they follow a similar behavior as those reported in the literature.
Influence of molecular weight of modified ultrahigh-molecular-weight polyethylene with Cu(II) chelate of bissalicylaldehydeethylenediamine on wear-resistant materials
Authors: Liu Min , Wu Li , Zhang Fuqing , Fu Jing
Published: April 2016

Reciprocating friction and wear performances of pure ultrahigh-molecular-weight polyethylenes (UHMWPEs) with molecular weights (MWs) of 2, 3, 5, and 9 million and their modified UHMWPEs with 15 wt.% Cu(II) chelate of bissalicylaldehyde-ethylenediamine (add1) against titanium alloy (Ti6Al4V) were investigated under boundary lubrication with 25 vol.% calf serum deionized water solution. Differential scanning calorimetry (DSC) of purchased UHMWPE powders was performed. The enthalpy changed with an increase in MW. UH300 had the lowest temperature of an extrapolated peak and the best peak symmetry in DSC analysis. The friction coefficient curves of molded pure and modified UHMWPEs/Ti6Al4V were compared, and the volume loss by the wear of polymers was measured. 3D topographies of the worn surfaces of polymers and images of the worn surfaces of polymers and titanium alloy against polymers were analyzed by confocal white light microscopy and scanning electron microscopy, respectively. Results showed that the influence of MW of UHMWPE was obvious on the friction and wear characteristics of pure UHMWPEs and 15% add1 UHMWPEs. An MW of 3 million was the best to reduce the friction of rubbing pairs, enhance the wear resistance of pure UHMWPEs and 15% add1-UHMWPEs, and improve the mating properties of Ti6Al4V.
Blind spots in agri-environmental governance: some reflections and suggestions from Switzerland
Authors: Forney Jérémie
Published: April 2016

Attempts of making our food systems more sustainable have (partly) failed. Food production still contributes significantly to biodiversity losses, global warming and depletion of natural resources. Based on the postulation that this failure in the governance of environmental issues in agri-food systems relates notably to social and cultural aspects, this paper explores the literature in the social sciences looking for explanations. A first statement is that research around agri-environmental governance (AEG) issues remains globally split into two subgroups, one focusing on public policies and the other on the civil society or market aspects of environmental certification, with very little exchange or transversal analysis between the two. Drawing on the literature and on long-term fieldwork and research in Switzerland, I identify three dimensions of AEG that open new paths towards more sustainable food systems: an encompassing approach of the food system; the encouragement of collective knowledge creation and the promotion of autonomy. Joining other emerging scholarships, this paper calls for developments in the research on AEG that produce encompassing theoretical frameworks, which transcends pre-existing categories in order to allow new conceptualisation of governance practices in complex or hybrid systems. The integration of the food, knowledge and autonomy dimensions should help in creating innovative and transformative governance instruments.
Is the Stellar System WR 11 a Gamma-Ray Source?
Authors: Benaglia Paula
Published: April 2016

Many early-type stars are in systems; some of them have been indicated as putative high-energy emitters. The radiation would be produced at the region where two stellar winds collide. Compelling evidence of such emission was found only for the colliding-wind binary (CWB) Eta Car, which was associated to a GeV source. Very recently, the closest CWB, WR 11, was proposed as a counterpart of a 6σ emission excess, measured with the Fermi LAT satellite. We sought evidence to support or reject the hypothesis that WR 11 is responsible of the gamma-ray excess. Archive radio interferometric data at 1.4 and 2.5 GHz taken with the Australia Telescope Compact Array along 16 dates were reduced. The sizes of the field-of-view at 2.5 GHz and of the central region of the Fermi LAT excess are alike. We analysed the emission of the WR 11 field, characterised the radio sources detected and derived their spectral indices, to investigate their nature. Eight sources with fluxes above 10 mJy were detected at both frequencies. All but one (WR 11) showed negative spectral indices. Four of them were identified with known objects, including WR 11. A fifth source, labeled here S6, is a promising candidate to produce gamma-ray emission, besides the CWB WR 11.
Social Norms after Conflict Exposure and Victimization by Violence: Experimental Evidence from Kosovo
Authors: Mironova Vera , Whitt Sam
Published: April 2016

An emerging literature points to the heterogeneous effects of violence on social norms and preferences in conflict-ridden societies. This article considers how responses to violence could be affected by in-group/out-group divisions. The research uses lab-in-the-field experiments to gauge norms for pro-social behavior in the aftermath of ethnic violence in post-war Kosovo. The study finds that one set of treatments (ethnicity) captures a negative legacy of violence on parochialism, while another (local/non-local) shows stronger evidence of pro-sociality and norm recovery. Examining individual variation in conflict exposure, it finds that victims of violence are more biased against ethnic out-groups and less pro-social to others outside of their local community. Balancing and matching on observables helps alleviate concerns that the results are driven by selection bias on victimization. Overall, the results suggest that the effects of violence may be contingent on the salience of in-group/out-group cues and boundaries.
Reproductive isolation between two populations ofDiatraea saccharalis(F.) (Lepidoptera: Crambidae) from different host plant species and regions in Argentina
Authors: Fogliata S.V. , Vera A. , Gastaminza G. , Cuenya M.I. , Zucchi M.I. , Willink E. , Castagnaro A.P. , Murúa M.G.
Published: April 2016

The sugarcane borer,Diatraea saccharalis(F.), has a widespread distribution throughout the Western Hemisphere and is a pest of many crop plants including sugarcane, corn, sorghum and rice. The use ofBacillus thuringiensis(Bt) corn has been the primary tool for managing this species in corn fields. Sugarcane borer control has been recently threatened by observations of susceptibility and/or resistance to certain varieties of Bt corn and the protein used in many newer varieties. This has led to increased interest in understanding sugarcane borer genetic diversity and gene flow within and among its populations and the consequent exchange of alleles between geographically distant populations. The objective of this study was to examine reproductive compatibility between host-associated geographic populations ofD. saccharalisin Argentina and to determine whether this pest represents a complex of host-associated cryptic species rather than a wide ranging generalist species. Intra and inter-population crosses revealed thatD. saccharalispopulations from the northwestern and Pampas regions presented evidence of prezygotic and postzygotic incompatibility. Such a result is likely to be the product of an interruption of gene flow produced by either geographic or host plant associated isolation, suggesting that Tucumán (northwestern) and Buenos Aires (Pampas) populations ofD. saccharalisare a distinct genotype and possibly an incipient species.
Matter Unmoored: Trash, Archaeological Consciousness and American Culture and Fiction in the 1980s
Authors: JELFS TIM
Published: April 2016

This article considers the cultural significance of the garbage panics of the 1980s, including the voyage of the infamous Mobro 4000 “garbage barge.” The article argues that the trash at the centre of these panics is important to our understanding of both the 1980s and the present because it demanded – and still demands – that Americans see and understand it as a class of matter unmoored from temporal as well as spatial boundaries. The alarming durability of the supposedly ephemeral refuse of a culture of mass consumption invoked an “archaeological consciousness” prone to muse upon the longevity of material remains. This consciousness was expressed in various cultural and discursive arenas throughout the 1980s, revealing that durable detritus was not just a pressing public policy issue but a marker of cultural anxieties emerging out of the operations of archaeological consciousness. From concerns about contingency of the mass-consuming culture of the late twentieth-century United States to reflections on trash's own epistemological complexity, trash spoke in unexpected ways throughout the 1980s, raising important questions about the relationship between producers of culture and their audience, whose receptiveness to the urgencies of archaeological consciousness suffers from a frustrating transience as far as trash is concerned.
Taking a stand against illegal wildlife trade: the Zimbabwean approach to pangolin conservation
Authors: Shepherd Chris R. , Connelly Ellen , Hywood Lisa , Cassey Phillip
Published: April 2016

Pangolins are increasingly threatened by demand for their scales, which are used in traditional medicines, and for their meat, which is consumed as a luxury. As populations of Asian pangolins decline, the demand is shifting to the four species in Africa, where local cultural use may already pose some level of threat. During 2010−2015 a total of 65 pangolin-related seizures (surrendered and confiscated) were reported in Zimbabwe, with the annual number of confiscations increasing significantly over this period. Zimbabwean authorities have toughened their stance against this trade, and during January−June 2015 three-quarters of confiscations of pangolins (n = 12) resulted in the maximum jail sentence for at least one of the offenders in each case. At present there is no evidence that pangolins are being traded from Zimbabwe to China, and the increased enforcement may be key to ensuring Zimbabwe's pangolins are not threatened by the large-scale illegal trade witnessed in Asia.
Retirement Policies and Support for Emergency Service Personnel: The Transition to Retirement
Authors: Bracken-Scally Mairéad , McGilloway Sinéad , Mitchell Jeffrey T.
Published: April 2016

L’objectif principal de cette étude a été d’examiner les politiques et les procédures pour soutenir les employés prenant leur retraite de leur travail aux services d’urgence. On a mené des entrevues avec les participants qui connaissaient bien les politiques et les procédures actuelles d’un grand ambulance (n= 8) et le service d’incendie (n= 6) en Irlande. Quatre thèmes principaux ont été révelés: (1) «Je ne pense pas que ce soit un bon travail d’etre ambulancier d’urgence quand on a 65 ans»; (2) “ils se sentent véritablement un tout petit peu isolé”; (3) l’amélioration du «choc culturel»; et (4) «Je continue a m’avancer en espérant que tout aille pour le mieux. » Les conclusions indiquent que la retraite est un changement majeur de la vie, et mettent en évidence la nécessité pour une préparation de pré-retraite plus structurée et efficace. Les éléments uniques au personnel des services d’urgence comprennent: le stress physique et émotionnel intense impliqué dans les services d’urgence; une forte identification avec ce service; et un manque de clarté sur les règles et les droits, exigeant meilleure renseignements et préparation pour prendre sa retraite.
Impedance transforming directional couplers with increased achievable transformation ratio
Authors: Sorocki Jakub , Piekarz Ilona , Wincza Krzysztof , Gruszczynski Slawomir
Published: April 2016

Novel impedance transforming directional couplers are proposed in which the achievable impedance transformation ratio is increased above the previously reported limit related to coupling of the coupled-line sections. The proposed couplers consist of two coupled-line sections between which uncoupled sections of left-handed lines are connected. The presented concept has been verified by circuit simulations as well as by measurements of the manufactured 3-dB coupled-line impedance transforming directional coupler operating at f0 = 1.2 GHz and featuring twofold increased impedance transformation ratio R = 4.
Ionospheric Waves Linked to Polar Atmospheric Dynamics
Authors: Knizhnik Kalman
Published: April 2016

Ionospheric waves are likely to be caused by processes in the polar atmosphere rather than by space weather.
TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease
Authors: Wu Mengrui , Chen Guiqian , Li Yi-Ping
Published: April 2016

Transforming growth factor-beta (TGF-β) and bone morphogenic protein (BMP) signaling has fundamental roles in both embryonic skeletal development and postnatal bone homeostasis. TGF-βs and BMPs, acting on a tetrameric receptor complex, transduce signals to both the canonical Smad-dependent signaling pathway (that is, TGF-β/BMP ligands, receptors, and Smads) and the non-canonical-Smad-independent signaling pathway (that is, p38 mitogen-activated protein kinase/p38 MAPK) to regulate mesenchymal stem cell differentiation during skeletal development, bone formation and bone homeostasis. Both the Smad and p38 MAPK signaling pathways converge at transcription factors, for example, Runx2 to promote osteoblast differentiation and chondrocyte differentiation from mesenchymal precursor cells. TGF-β and BMP signaling is controlled by multiple factors, including the ubiquitin–proteasome system, epigenetic factors, and microRNA. Dysregulated TGF-β and BMP signaling result in a number of bone disorders in humans. Knockout or mutation of TGF-β and BMP signaling-related genes in mice leads to bone abnormalities of varying severity, which enable a better understanding of TGF-β/BMP signaling in bone and the signaling networks underlying osteoblast differentiation and bone formation. There is also crosstalk between TGF-β/BMP signaling and several critical cytokines’ signaling pathways (for example, Wnt, Hedgehog, Notch, PTHrP, and FGF) to coordinate osteogenesis, skeletal development, and bone homeostasis. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in osteoblast differentiation, chondrocyte differentiation, skeletal development, cartilage formation, bone formation, bone homeostasis, and related human bone diseases caused by the disruption of TGF-β/BMP signaling.
Highly selective hydrogenation of arenes using nanostructured ruthenium catalysts modified with a carbon–nitrogen matrix
Authors: Cui Xinjiang , Surkus Annette-Enrica , Junge Kathrin , Topf Christoph , Radnik Jörg , Kreyenschulte Carsten , Beller Matthias
Published: April 2016

Selective hydrogenations of (hetero)arenes represent essential processes in the chemical industry, especially for the production of polymer intermediates and a multitude of fine chemicals. Herein, we describe a new type of well-dispersed Ru nanoparticles supported on a nitrogen-doped carbon material obtained from ruthenium chloride and dicyanamide in a facile and scalable method. These novel catalysts are stable and display both excellent activity and selectivity in the hydrogenation of aromatic ethers, phenols as well as other functionalized substrates to the corresponding alicyclic reaction products. Furthermore, reduction of the aromatic core is preferred over hydrogenolysis of the C–O bond in the case of ether substrates. The selective hydrogenation of biomass-derived arenes, such as lignin building blocks, plays a pivotal role in the exploitation of novel sustainable feedstocks for chemical production and represents a notoriously difficult transformation up to now.
Ultrasound modulates ion channel currents
Authors: Kubanek Jan , Shi Jingyi , Marsh Jon , Chen Di , Deng Cheri , Cui Jianmin
Published: April 2016

Transcranial focused ultrasound (US) has been demonstrated to stimulate neurons in animals and humans, but the mechanism of this effect is unknown. It has been hypothesized that US, a mechanical stimulus, may mediate cellular discharge by activating mechanosensitive ion channels embedded within cellular membranes. To test this hypothesis, we expressed potassium and sodium mechanosensitive ion channels (channels of the two-pore-domain potassium family (K2P) including TREK-1, TREK-2, TRAAK; NaV1.5) in the Xenopus oocyte system. Focused US (10 MHz, 0.3–4.9 W/cm2) modulated the currents flowing through the ion channels on average by up to 23%, depending on channel and stimulus intensity. The effects were reversible upon repeated stimulation and were abolished when a channel blocker (ranolazine to block NaV1.5, BaCl2 to block K2P channels) was applied to the solution. These data reveal at the single cell level that focused US modulates the activity of specific ion channels to mediate transmembrane currents. These findings open doors to investigations of the effects of US on ion channels expressed in neurons, retinal cells, or cardiac cells, which may lead to important medical applications. The findings may also pave the way to the development of sonogenetics: a non-invasive, US-based analogue of optogenetics.
On residual stresses and homeostasis: an elastic theory of functional adaptation in living matter
Authors: Ciarletta P. , Destrade M. , Gower A. L.
Published: April 2016

Living matter can functionally adapt to external physical factors by developing internal tensions, easily revealed by cutting experiments. Nonetheless, residual stresses intrinsically have a complex spatial distribution and destructive techniques cannot be used to identify a natural stress-free configuration. This work proposes a novel elastic theory of pre-stressed materials. Imposing physical compatibility and symmetry arguments, we define a new class of free energies explicitly depending on the internal stresses. This theory is finally applied to the study of arterial remodelling, proving its potential for the non-destructive determination of the residual tensions within biological materials.
Combining measurements to estimate properties and characterization extent of complex biochemical mixtures; applications to Heparan Sulfate
Authors: Pradines Joël R. , Beccati Daniela , Lech Miroslaw , Ozug Jennifer , Farutin Victor , Huang Yongqing , Gunay Nur Sibel , Capila Ishan
Published: April 2016

Complex mixtures of molecular species, such as glycoproteins and glycosaminoglycans, have important biological and therapeutic functions. Characterization of these mixtures with analytical chemistry measurements is an important step when developing generic drugs such as biosimilars. Recent developments have focused on analytical methods and statistical approaches to test similarity between mixtures. The question of how much uncertainty on mixture composition is reduced by combining several measurements still remains mostly unexplored. Mathematical frameworks to combine measurements, estimate mixture properties and quantify remaining uncertainty, i.e. a characterization extent, are introduced here. Constrained optimization and mathematical modeling are applied to a set of twenty-three experimental measurements on heparan sulfate, a mixture of linear chains of disaccharides having different levels of sulfation. While this mixture has potentially over two million molecular species, mathematical modeling and the small set of measurements establish the existence of nonhomogeneity of sulfate level along chains and the presence of abundant sulfate repeats. Constrained optimization yields not only estimations of sulfate repeats and sulfate level at each position in the chains but also bounds on these levels, thereby estimating the extent of characterization of the sulfation pattern which is achieved by the set of measurements.
Proteomic dissection of LPS-inducible, PHF8-dependent secretome reveals novel roles of PHF8 in TLR4-induced acute inflammation and T cell proliferation
Authors: Erdoğan Özgün , Xie Ling , Wang Li , Wu Bing , Kong Qing , Wan Yisong , Chen Xian
Published: April 2016

Endotoxin (LPS)-induced changes in histone lysine methylation contribute to the gene-specific transcription for control of inflammation. Still unidentified are the chromatin regulators that drive the transition from a transcriptional-repressive to a transcriptional-active chromatin state of pro-inflammatory genes. Here, using combined approaches to analyze LPS-induced changes in both gene-specific transcription and protein secretion to the extracellular compartment, we characterize novel functions of the lysine demethylase PHF8 as a pro-inflammatory, gene-specific chromatin regulator. First, in the LPS-induced, acute-inflamed macrophages, PHF8 knockdown led to both a reduction of pro-inflammatory factors and an increase in a transcriptional-repressive code (H3K9me2) written by the methyltransferase G9a. Through unbiased quantitative secretome screening we discovered that LPS induces the secretion of a cluster of PHF8-dependent, ‘tolerizable’ proteins that are related to diverse extracellular pathways/processes including those for the activation of adaptive immunity. Specifically, we determined that PHF8 promotes T-cell activation and proliferation, thus providing the first link between the epigenetic regulation of inflammation and adaptive immunity. Further, we found that, in the acute-inflamed macrophages, the acute-active PHF8 opposes the H3K9me1/2-writing activity of G9a to activate specific protein secretions that are suppressed by G9a in the endotoxin-tolerant cells, revealing the inflammatory-phenotypic chromatin drivers that regulate the gene-specific chromatin plasticity.
Dietary flavonoid intake and the risk of digestive tract cancers: a systematic review and meta-analysis
Authors: Bo Yacong , Sun Jinfeng , Wang Mengmeng , Ding Jizhe , Lu Quanjun , Yuan Ling
Published: April 2016

Several epidemiological studies have investigated the association between dietary flavonoid intake and digestive tract cancers risk; however, the results remain inconclusive. The aim of our study was to evaluate this association. PubMed and the Web of Knowledge were searched for relevant publications from inception to October 2015. The risk ratio (RR) or odds ratio (OR) with the 95% confidence interval (95% CI) for the highest versus the lowest categories of flavonoid intake were pooled using a fixed-effects model. A total of 15 articles reporting 23 studies were selected for the meta-analysis. In a comparison of the highest versus the lowest categories of dietary flavonoid intake, we found no significant association between flavonoid intake and oesophageal cancer (OR = 0.91, 95% CI = 0.75–1.10; I2 = 0.0%), colorectal cancer (OR = 1.02, 95% CI = 0.92–1.14, I2 = 36.2%) or gastric cancer (OR = 0.88; 95% CI = 0.74–1.04, I2 = 63.6%). The subgroup analysis indicated an association between higher flavonoid intake and a decreased risk of gastric cancer in the European population (OR = 0.78, 95% CI = 0.62–0.97). In conclusion, the results of this meta-analysis do not strongly support an association between dietary flavonoid intake and oesophageal or colorectal cancer. Furthermore, the subgroup analysis suggested an association between higher dietary flavonoid intake and decreased gastric cancer risk in European population.
Fisetin stimulates autophagic degradation of phosphorylated tau via the activation of TFEB and Nrf2 transcription factors
Authors: Kim Sunhyo , Choi Ki Ju , Cho Sun-Jung , Yun Sang-Moon , Jeon Jae-Pil , Koh Young Ho , Song Jihyun , Johnson Gail V. W. , Jo Chulman
Published: April 2016

The neuronal accumulation of phosphorylated tau plays a critical role in the pathogenesis of Alzheimer’s disease (AD). Here, we examined the effect of fisetin, a flavonol, on tau levels. Treatment of cortical cells or primary neurons with fisetin resulted in significant decreases in the levels of phosphorylated tau. In addition, fisetin decreased the levels of sarkosyl-insoluble tau in an active GSK-3β-induced tau aggregation model. However, there was no difference in activities of tau kinases and phosphatases such as protein phosphatase 2A, irrespective of fisetin treatment. Fisetin activated autophagy together with the activation of transcription factor EB (TFEB) and Nrf2 transcriptional factors. The activation of autophagy including TFEB is likely due to fisetin-mediated mammalian target of rapamycin complex 1 (mTORC1) inhibition, since the phosphorylation levels of p70S6 kinase and 4E-BP1 were decreased in the presence of fisetin. Indeed, fisetin-induced phosphorylated tau degradation was attenuated by chemical inhibitors of the autophagy-lysosome pathway. Together the results indicate that fisetin reduces levels of phosphorylated tau through the autophagy pathway activated by TFEB and Nrf2. Our result suggests fisetin should be evaluated further as a potential preventive and therapeutic drug candidate for AD.
Accurate measurement of liquid transport through nanoscale conduits
Authors: Alibakhshi Mohammad Amin , Xie Quan , Li Yinxiao , Duan Chuanhua
Published: April 2016

Nanoscale liquid transport governs the behaviour of a wide range of nanofluidic systems, yet remains poorly characterized and understood due to the enormous hydraulic resistance associated with the nanoconfinement and the resulting minuscule flow rates in such systems. To overcome this problem, here we present a new measurement technique based on capillary flow and a novel hybrid nanochannel design and use it to measure water transport through single 2-D hydrophilic silica nanochannels with heights down to 7 nm. Our results show that silica nanochannels exhibit increased mass flow resistance compared to the classical hydrodynamics prediction. This difference increases with decreasing channel height and reaches 45% in the case of 7 nm nanochannels. This resistance increase is attributed to the formation of a 7-angstrom-thick stagnant hydration layer on the hydrophilic surfaces. By avoiding use of any pressure and flow sensors or any theoretical estimations the hybrid nanochannel scheme enables facile and precise flow measurement through single nanochannels, nanotubes, or nanoporous media and opens the prospect for accurate characterization of both hydrophilic and hydrophobic nanofluidic systems.
A direct assessment of human prion adhered to steel wire using real-time quaking-induced conversion
Authors: Mori Tsuyoshi , Atarashi Ryuichiro , Furukawa Kana , Takatsuki Hanae , Satoh Katsuya , Sano Kazunori , Nakagaki Takehiro , Ishibashi Daisuke , Ichimiya Kazuko , Hamada Masahisa , Nakayama Takehisa , Nishida Noriyuki
Published: April 2016

Accidental transmission of prions during neurosurgery has been reported as a consequence of re-using contaminated surgical instruments. Several decontamination methods have been studied using the 263K-hamster prion; however, no studies have directly evaluated human prions. A newly developed in vitro amplification system, designated real-time quaking-induced conversion (RT-QuIC), has allowed the activity of abnormal prion proteins to be assessed within a few days. RT-QuIC using human recombinant prion protein (PrP) showed high sensitivity for prions as the detection limit of our assay was estimated as 0.12 fg of active prions. We applied this method to detect human prion activity on stainless steel wire. When we put wires contaminated with human Creutzfeldt–Jakob disease brain tissue directly into the test tube, typical PrP-amyloid formation was observed within 48 hours, and we could detect the activity of prions at 50% seeding dose on the wire from 102.8 to 105.8 SD50. Using this method, we also confirmed that the seeding activities on the wire were removed following treatment with NaOH. As seeding activity closely correlated with the infectivity of prions using the bioassay, this wire-QuIC assay will be useful for the direct evaluation of decontamination methods for human prions.
ESCRT-0 dysfunction compromises autophagic degradation of protein aggregates and facilitates ER stress-mediated neurodegeneration via apoptotic and necroptotic pathways
Authors: Oshima Ryuji , Hasegawa Takafumi , Tamai Keiichi , Sugeno Naoto , Yoshida Shun , Kobayashi Junpei , Kikuchi Akio , Baba Toru , Futatsugi Akira , Sato Ikuro , Satoh Kennichi , Takeda Atsushi , Aoki Masashi , Tanaka Nobuyuki
Published: April 2016

Endosomal sorting required for transport (ESCRT) complexes orchestrate endo-lysosomal sorting of ubiquitinated proteins, multivesicular body formation and autophagic degradation. Defects in the ESCRT pathway have been implicated in many neurodegenerative diseases, but the underlying molecular mechanisms that link them to neurodegeneration remain unknown. In this study, we showed that forebrain-specific ablation of ESCRT-0/Hrs induced marked hippocampal neuronal cell loss accompanied by the accumulation of ubiquitinated proteins, including α-synuclein, TDP-43 and huntingtin as well as the autophagic substrate SQSTM1/p62. Consistent with this, silencing of Hrs in cultured cells not only led to α-synuclein and TDP-43 accumulation in addition to impaired autophagic flux but also suppressed cell viability through the induction of ER stress followed by the activation of JNK and RIPK1, a key regulator of necroptosis. Moreover, necrostatin-1, a specific inhibitor of RIPK1 and pan-caspase inhibitors partially reduced the neurotoxicity in the Hrs-silenced cells. Altogether, these findings suggest that the disruption of ESCRT-0/Hrs in the nervous system compromises autophagic/lysosomal degradation of neurodegenerative disease-related proteins, which thereby triggers ER stress-mediated apoptotic and necroptotic cell death.
Chronic obstructive pulmonary disease effect on the prevalence and postoperative outcome of abdominal aortic aneurysms: A meta-analysis
Authors: Xiong Jiang , Wu Zhongyin , Chen Chen , Guo Wei
Published: April 2016

Epidemiologic evidence suggested chronic obstructive pulmonary disease (COPD) might increase risk for abdominal aortic aneurysm (AAA). However, the association between COPD and AAA remains inconclusive. We searched PubMed and Cochrane databases until June 2015. Forty-eight articles were included for meta-analysis. COPD was found to be positively associated with AAA, regardless of study design and smoking status. AAA mortality is higher among COPD patients compared with non-COPD patients (postoperative [adjusted OR 2.11; 95% CI 1.33–3.34]; long-term [adjusted OR 1.70; 95% CI 1.37–2.12]). But the association between postoperative mortality and COPD was not found to be significant in patients underwent endovascular aneurysm repair (mixed OR 2.53; 95% CI 0.70–9.18). Rupture AAA may increase the postoperative mortality in COPD patients (rupture [adjusted OR 4.75; 95% CI 2.07–10.89]; non-rupture [adjusted OR 1.97; 95% CI 1.11–3.49]). The AAA postoperative morbidity was found to be positively associated with COPD (adjusted OR 1.59; 95% CI 1.14–2.21). Increased COPD severity may increase the long-term mortality (medical versus oxygen dependent: [OR 1.26; 95% CI 1.07–1.49] versus [OR 2.79; 95% CI 2.24–3.49]). In conclusion, COPD may increase the risk of AAA, morbidity and mortality of AAA patients underwent endovascular aortic repair.
Bright-field Nanoscopy: Visualizing Nano-structures with Localized Optical Contrast Using a Conventional Microscope
Authors: Suran Swathi , Bharadwaj Krishna , Raghavan Srinivasan , Varma Manoj M.
Published: April 2016

Most methods for optical visualization beyond the diffraction limit rely on fluorescence emission by molecular tags. Here, we report a method for visualization of nanostructures down to a few nanometers using a conventional bright-field microscope without requiring additional molecular tags such as fluorophores. The technique, Bright-field Nanoscopy, is based on the strong thickness dependent color of ultra-thin germanium on an optically thick gold film. We demonstrate the visualization of grain boundaries in chemical vapour deposited single layer graphene and the detection of single 40 nm Ag nanoparticles. We estimate a size detection limit of about 2 nm using this technique. In addition to visualizing nano-structures, this technique can be used to probe fluid phenomena at the nanoscale, such as transport through 2D membranes. We estimated the water transport rate through a 1 nm thick polymer film using this technique, as an illustration. Further, the technique can also be extended to study the transport of specific ions in the solution. It is anticipated that this technique will find use in applications ranging from single-nanoparticles resolved sensing to studying nanoscale fluid-solid interface phenomena.
Efficient Generation of Myostatin Gene Mutated Rabbit by CRISPR/Cas9
Authors: Lv Qingyan , Yuan Lin , Deng Jichao , Chen Mao , Wang Yong , Zeng Jian , Li Zhanjun , Lai Liangxue
Published: April 2016

CRISPR/Cas9 has been widely used in generating site-specific genetically modified animal models. Myostatin (MSTN) is a negative regulator of muscle mass, related to muscle growth and differentiation. The knockout of MSTN with the desired phenotype of double muscle has been successfully generated in mice, goats, pigs and cattle, but not in rabbits. In this study, the MSTN knockout (KO) rabbits were generated by co-injection of Cas9 mRNA and sgRNA into zygotes. The typical phenotype of double muscle with hyperplasia or hypertrophy of muscle fiber was observed in MSTN KO rabbits. Furthermore, a similar phenotype was found in the F1 generation, suggesting that the mutation of MSTN could be stably inherited in the MSTN KO rabbits. In summary, we have successfully generated MSTN KO rabbits using CRISPR/Cas9 system with high efficiency, which is a reliable and effective animal model for the study of muscle development and related diseases.
Comparing watershed black locust afforestation and natural revegetation impacts on soil nitrogen on the Loess Plateau of China
Authors: Jin Zhao , Li Xiangru , Wang Yunqiang , Wang Yi , Wang Kaibo , Cui Buli
Published: April 2016

This study examined a pair of neighbouring small watersheds with contrasting vegetations: artificial forestland and natural grassland. Since 1954, afforestation which mainly planted with black locust has been conducted in one of these watersheds and natural revegetation in the other. The differences in soil total N, nitrate, ammonium, foliar litterfall δ15N and dual stable isotopes of δ15N and δ18O in soil nitrate were investigated in the two ecosystems. Results showed that there was no significant difference in soil total N storage between the two ecosystems, but the black locust forestland presented higher soil nitrate than the grassland. Moreover, the foliar litterfall N content and δ15N of the forestland were significant higher than the grassland. These results indicate that 60 years of watershed black locust afforestation have increased soil N availability. The higher nitrate in the forestland was attributed to the biological N fixation of black locust and difference in ecosystem hydrology. The dual stable isotopes of δ15N and δ18O revealed that the two ecosystems had different sources of soil nitrate. The soil nitrate in the forestland was likely derived from soil N nitrification, while the soil nitrate in the grassland was probably derived from the legacy of NO3− fertiliser.
Magnetic neutron scattering by magnetic vortices in thin submicron-sized soft ferromagnetic cylinders
Authors: Metlov Konstantin L. , Michels Andreas
Published: April 2016

Using analytical expressions for the magnetization textures of thin submicron-sized magnetic cylinders in vortex state, we derive closed-form algebraic expressions for the ensuing small-angle neutron scattering (SANS) cross sections. Specifically, for the perpendicular and parallel scattering geometries, we have computed the cross sections for the case of small vortex-center displacements without formation of magnetic charges on the side faces of the cylinder. The results represent a significant qualitative and quantitative step forward in SANS-data analysis on isolated magnetic nanoparticle systems, which are commonly assumed to be homogeneously or stepwise-homogeneously magnetized. We suggest a way to extract the fine details of the magnetic vortex structure during the magnetization process from the SANS measurements in order to help resolving the long-standing question of the magnetic vortex displacement mode.
The Csr system regulates genome-wide mRNA stability and transcription and thus gene expression in Escherichia coli
Authors: Esquerré Thomas , Bouvier Marie , Turlan Catherine , Carpousis Agamemnon J. , Girbal Laurence , Cocaign-Bousquet Muriel
Published: April 2016

Bacterial adaptation requires large-scale regulation of gene expression. We have performed a genome-wide analysis of the Csr system, which regulates many important cellular functions. The Csr system is involved in post-transcriptional regulation, but a role in transcriptional regulation has also been suggested. Two proteins, an RNA-binding protein CsrA and an atypical signaling protein CsrD, participate in the Csr system. Genome-wide transcript stabilities and levels were compared in wildtype E. coli (MG1655) and isogenic mutant strains deficient in CsrA or CsrD activity demonstrating for the first time that CsrA and CsrD are global negative and positive regulators of transcription, respectively. The role of CsrA in transcription regulation may be indirect due to the 4.6-fold increase in csrD mRNA concentration in the CsrA deficient strain. Transcriptional action of CsrA and CsrD on a few genes was validated by transcriptional fusions. In addition to an effect on transcription, CsrA stabilizes thousands of mRNAs. This is the first demonstration that CsrA is a global positive regulator of mRNA stability. For one hundred genes, we predict that direct control of mRNA stability by CsrA might contribute to metabolic adaptation by regulating expression of genes involved in carbon metabolism and transport independently of transcriptional regulation.