bluuebunny/crossref_metadata_2025 huggingface dataset:
Growing Apart? Partisan Sorting in Canada, 1992–2015
Authors: Kevins Anthony , Soroka Stuart N.
Published: August 2017

Recent decades have been marked by increasingly divided partisan opinion in the US. This study investigates whether a similar trend might be occurring in Canada. It does so by examining redistributive preferences, using Canadian Election Studies data from every election since 1992. Results suggest that Canada has experienced a surge in partisan sorting that is comparable to that in the US. Over time, like-minded citizens have increasingly clustered into parties, with increasingly stark divisions between partisans.
A survey of management practices and flock performance and their association with flock size and ewe breed type on Irish sheep farms
Authors: BOHAN A. , SHALLOO L. , CREIGHTON P. , BOLAND T. M. , MCHUGH N.
Published: August 2017

A detailed survey was undertaken to assess the rate of production and current management practices on Irish sheep farms and quantify their associations with flock size and ewe breed type. A total of 39 questions relating to the farm production system and farm management practices were devised, including: producer age, location, farm size, livestock numbers and type, in addition to flock management data such as flock breeding policy, lamb finishing strategy, flock health, lambing date, winter housing and feeding practices. A total of 717 sheep producers were surveyed across 45 different discussion groups. The surveyed respondents were sub-divided into four groups depending on flock size (very small, small, medium and large) and into three groups depending on ewe breed type (maternal, terminal and hill). The average survey respondent was 48 years old, with a flock size of 150 breeding ewes on a farm size of 58 ha. The average stocking rates were 6·55 and 3·14 ewes/ha and weaning rates were 1·44 and 1·02 lambs per ewe joined to the ram for the lowland and hill flocks, respectively. Relative to very small flocks (<62 ewes), larger flocks (>190 ewes) had higher stocking rates (6·98v.5·66 ewes/ha) and ewe to ram ratios (40v.30), and tended to lamb later in the year. The rate of technology adoption such as faecal egg sampling and pregnancy scanning was greater on larger flocks compared with smaller flocks. Flocks with maternal ewe breeds had higher scanning and weaning rates, and drafted a greater proportion of lambs off grass compared with flocks with terminal and hill ewe breeds. Flocks with maternal and terminal ewe breed types were more likely to winter house ewes, lamb indoors, test silage quality and have a handling unit compared with flocks with hill-type ewe breeds. Results from the present study provide a bank of knowledge on current Irish sheep industry performance and show that flock size and ewe breed type have a significant impact on key flock performance variables.
Film-mulched maize production: response to controlled-release urea fertilization
Authors: GUO J. M. , XUE J. Q. , BLAYLOCK A. D. , CUI Z. L. , CHEN X. P.
Published: August 2017

Optimal nitrogen (N) management for maize in the film-mulched production systems that are widely used in dryland agriculture is difficult because top-dressing N is impractical. The current research determined how matching N supply and demand was achieved before and after silking stages, when single applications of controlled release urea (CRU) were combined with conventional urea in film-mulched maize production. The CRU: urea mixture was applied in a 1 : 2 or 2 : 1 ratio and all three fertilizer regimes (urea alone and CRU: urea at 1 : 2 or 2 : 1) were applied at N rates of 180 and 240 kg/ha over 2 years. The 1 : 2 CRU: urea mixture, applied once at 180 kg N/ha, was found to synchronize N supply with demand, thereby reducing N losses. The highest grain yields (11·8–12·0 t/ha), N uptake (232–239 kg/ha), N recovery (65·8–67·7%) and high net economic return were achieved with this regime. These results indicate that a single application of a mixture of CRU and urea can synchronize N supply with demand and provide higher yields and profits than conventional N fertilization in film-mulched maize systems.
The same but different: stable isotopes reveal two distinguishable, yet similar, neighbouring food chains in a coral reef
Authors: Le Bourg Baptiste , Letourneur Yves , Bănaru Daniela , Blanchot Jean , Chevalier Cristèle , Mou-Tham Gérard , Lebreton Benoit , Pagano Marc
Published: August 2017

Stable isotope compositions were studied in particulate organic matter (POM), zooplankton and different trophic groups of teleosts to compare food chains based on plankton at two sites (lagoon and outer slope) in a New Caledonian coral reef. For each trophic compartment, δ13C values were always lower in the outer slope than in the lagoon. This result may be explained by potential differences in POM composition between the two environments, suggesting that the two food chains are based on different primary sources of carbon. In contrast, δ15N values did not vary between the lagoon and the outer slope, indicating that these two food chains presented similar length and trophic levels, despite being distinguishable.
Development and growth in skulls of three Otariidae species: a comparative morphometric study
Authors: Sanfelice Daniela , Molina-Schiller Daniza , De Freitas Thales R. O.
Published: August 2017

We examined the skulls ofArctocephalus australis,Callorhinus ursinusandOtaria byroniawith the objectives of (1) estimating the development and growth rates and comparing these parameters among the species; (2) describing the development for each linear measure, for each species and sex; (3) determining which variables are best correlated with age; (4) determining age of physical maturity. We employed traditional and geometric morphometric techniques to study the skulls. InA. australisandC. ursinus, skulls of females mature at about 6 years of age, and those of males at about 8 years.Otaria byroniamatures later, at about 9 years. Using geometric morphometric data sets, the rate and constant of growth inA. australisdid not differ between the sexes.Callorhinus ursinusandO. byroniashowed rates significantly different between sexes concerning growth (and in the constant as well), but onlyO. byroniadiffered between sexes in both developmental model parameters (rates and constant). Comparisons between the growth and developmental models showed significant differences in slope and constant. In both treatments employed, a relationship between size and shape dimorphism could be inferred for the skulls of all three species. We conclude that rates or timing of growth and development evolves within a conserved spatiotemporal organization of morphogenesis.
Homogeneous chaos basis adaptation for design optimization under uncertainty: Application to the oil well placement problem
Authors: Thimmisetty Charanraj , Tsilifis Panagiotis , Ghanem Roger
Published: August 2017

A new method is proposed for efficient optimization under uncertainty that addresses the curse of dimensionality as it pertains to the evaluation of probabilistic objectives and constraints. A basis adaptation strategy previously introduced by the authors is integrated into a design optimization framework that construes the optimization cost function as the quantity of interest and computes stochastic adapted bases as functions of design space parameters. With these adapted bases, the stochastic integrations at each design point are evaluated as low-dimensional integrals (mostly one dimensional). The proposed approach is demonstrated on a well-placement problem where the uncertainty is in the form of a stochastic process describing the permeability of the subsurface. An analysis of the method is carried out to better understand the effect of design parameters on the smoothness of the adaptation isometry.
Outbreak ofSalmonella enteritidisphage type 1B associated with frozen pre-cooked chicken cubes, Finland 2012
Authors: HUUSKO S. , PIHLAJASAARI A. , SALMENLINNA S. , SÕGEL J. , DONTŠENKO I. , DE PINNA E. , LUNDSTRÖM H. , TOIKKANEN S. , RIMHANEN-FINNE R.
Published: August 2017

In August to October 2012, a nationwide outbreak ofSalmonella enteritidisphase type (PT) 1B with 53 cases occurred in Finland. Hypothesis generating interviews pointed toward ready-to-eat chicken salad from a Finnish company and at the same time Estonian authorities informed of aS. enteritidisPT 1B outbreak linked to chicken wrap prepared at an Estonian restaurant. We found that chicken salad was associated with the infection (odds ratio (OR) 16·1, 95% confidence interval (CI) 1·7–148·7 for consumption and OR 17·5. 95% CI 4·0–76·0 for purchase). The frozen pre-cooked chicken cubes used in Finnish salad and in Estonian wraps were traced back to a production plant in China. Great Britain made two Rapid Alert Systems for Food and Feed notifications on chicken cubes imported to the UK from the same Chinese production plant. Microbiological investigation confirmed that the patient isolates in Estonia and in Finland were indistinguishable from the strains isolated from chicken cubes in Estonia and in the UK. We recommend that despite certificates for testedSalmonella, food items should be analyzed whenSalmonellacontamination in outbreak investigations is suspected. In outbreak investigations, electronically implemented case–case study saves time, effort, and money compared with case–control study.
Transmission dynamics of lumpy skin disease in Ethiopia
Authors: MOLLA W. , FRANKENA K. , DE JONG M. C. M.
Published: August 2017

Lumpy skin disease (LSD) is a severe disease of cattle caused by a Capripoxvirus and often caused epidemics in Ethiopia and many other countries. This study was undertaken to quantify the transmission between animals and to estimate the infection reproduction ratio in a predominantly mixed crop–livestock system and in intensive commercial herd types. The transmission parameters were based on a susceptible-infectious-recovered (SIR) epidemic model with environmental transmission and estimated using generalized linear models. The transmission parameters were estimated using a survival rate of infectious virus in the environment equal to 0·325 per day, a value based on the best-fitting statistical model. The transmission rate parameter between animals was 0·072 (95% CI 0·068–0·076) per day in the crop–livestock production system, whereas this transmission rate in intensive production system was 0·076 (95% CI 0·068–0·085) per day. The reproduction ratio (R) of LSD between animals in the crop–livestock production system was 1·07, whereas it was 1·09 between animals in the intensive production system. The calculated R provides a baseline against which various control options can be assessed for efficacy.
Left main coronary artery atresia in a child: a case report and review of the literature
Authors: Hayashi Tomohiro , Waki Kenji , Arakaki Yoshio
Published: August 2017

Congenital atresia of the left coronary artery is a very rare condition. We report a case of a 13-year-old boy who was followed-up at our outpatient clinic from 6 months of age because of heart murmur. He had no symptoms for more than 10 years, and his left ventricular contraction was normal. Exercise electrocardiogram was performed at 7 and 10 years of age, and ST depression was not observed. He presented with chest pain and syncope on exertion at the ages of 11 and 12 years, respectively, and ST depression on exercise electrocardiogram was detected for the first time at 13 years of age. Cardiac echocardiography showed a high-choic antero-lateral papillary muscle of the mitral valve, prolapse of the mitral anterior leaflet, and mild mitral valve regurgitation. Coronary angiography did not demonstrate antegrade left coronary flow or dilation of the right coronary artery. We performed coronary artery bypass grafting using the left internal thoracic artery. Postoperatively, the ST depression resolved, and his exercise tolerability improved.
Hyperosmotic stress enhances cytotoxicity of SMAC mimetics
Authors: Bittner Sebastian , Knoll Gertrud , Ehrenschwender Martin
Published: August 2017

Inhibitors of apoptosis (IAP) proteins contribute to cell death resistance in malignancies and emerged as promising targets in cancer therapy. Currently, small molecules mimicking the IAP-antagonizing activity of endogenous second mitochondria-derived activator of caspases (SMAC) are evaluated in phase 1/2 clinical trials. In cancer cells, SMAC mimetic (SM)-mediated IAP depletion induces tumor necrosis factor (TNF) secretion and simultaneously sensitizes for TNF-induced cell death. However, tumor cells lacking SM-induced autocrine TNF release survive and thus limit therapeutic efficacy. Here, we show that hyperosmotic stress boosts SM cytotoxicity in human and murine cells through hypertonicity-induced upregulation of TNF with subsequent induction of apoptosis and/or necroptosis. Hypertonicity allowed robust TNF-dependent killing in SM-treated human acute lymphoblastic leukemia cells, which under isotonic conditions resisted SM treatment due to poor SM-induced TNF secretion. Mechanistically, hypertonicity-triggered TNF release bypassed the dependency on SM-induced TNF production to execute SM cytotoxicity, effectively reducing the role of SM to TNF-sensitizing, but not necessarily TNF-inducing agents. Perspectively, these findings could extend the clinical application of SM.
Uev1A facilitates osteosarcoma differentiation by promoting Smurf1-mediated Smad1 ubiquitination and degradation
Authors: Zhang Weiwei , Zhuang Yuan , Zhang Yiran , Yang Xiaoran , Zhang Hong , Wang Guifen , Yin Wanqi , Wang Ruifeng , Zhang Zhiling , Xiao Wei
Published: August 2017

Malignant bone tumor osteosarcoma (OS) displays high metastasis incidence and poor prognosis. Its stem cell properties could serve to explain tumor recurrence and resistance to conventional treatments. In this study, we identified UEV1A as a novel suppressor of OS. Elevated UEV1A diminishes stem cell properties of OS cells and drives them to terminal differentiation. Importantly, UEV1A-overexpressed OS cells delay proliferation and are more sensitive to chemotherapeutic agents than control cells. Uev1A appears to be involved in the BMP signaling pathway in which it collaborates with a ubiquitin E3 ligase Smurf1 to promote Smad1 degradation in a Ubc13-independent manner. Indeed, Smad1 is identified as a dominant downstream effector of Uev1A, which unravels the mechanism underlying Uev1A-orchestrated tumor suppression in OS. The above findings identify UEV1A as a potential OS tumor suppression gene, and shed lights to future OS diagnosis and treatment.
Oxidative coupling of sp
2 and sp
3 carbon–hydrogen bonds to construct dihydrobenzofurans
Authors: Shi Jiang-Ling , Wang Ding , Zhang Xi-Sha , Li Xiao-Lei , Chen Yu-Qin , Li Yu-Xue , Shi Zhang-Jie
Published: August 2017

Metal-catalyzed cross-couplings provide powerful, concise, and accurate methods to construct carbon–carbon bonds from organohalides and organometallic reagents. Recent developments extended cross-couplings to reactions where one of the two partners connects with an aryl or alkyl carbon–hydrogen bond. From an economic and environmental point of view, oxidative couplings between two carbon–hydrogen bonds would be ideal. Oxidative coupling between phenyl and “inert” alkyl carbon–hydrogen bonds still awaits realization. It is very difficult to develop successful strategies for oxidative coupling of two carbon–hydrogen bonds owning different chemical properties. This article provides a solution to this challenge in a convenient preparation of dihydrobenzofurans from substituted phenyl alkyl ethers. For the phenyl carbon–hydrogen bond activation, our choice falls on the carboxylic acid fragment to form the palladacycle as a key intermediate. Through careful manipulation of an additional ligand, the second “inert” alkyl carbon–hydrogen bond activation takes place to facilitate the formation of structurally diversified dihydrobenzofurans.
Annotating pathogenic non-coding variants in genic regions
Authors: Gelfman Sahar , Wang Quanli , McSweeney K. Melodi , Ren Zhong , La Carpia Francesca , Halvorsen Matt , Schoch Kelly , Ratzon Fanni , Heinzen Erin L. , Boland Michael J. , Petrovski Slavé , Goldstein David B.
Published: August 2017

Identifying the underlying causes of disease requires accurate interpretation of genetic variants. Current methods ineffectively capture pathogenic non-coding variants in genic regions, resulting in overlooking synonymous and intronic variants when searching for disease risk. Here we present the Transcript-inferred Pathogenicity (TraP) score, which uses sequence context alterations to reliably identify non-coding variation that causes disease. High TraP scores single out extremely rare variants with lower minor allele frequencies than missense variants. TraP accurately distinguishes known pathogenic and benign variants in synonymous (AUC = 0.88) and intronic (AUC = 0.83) public datasets, dismissing benign variants with exceptionally high specificity. TraP analysis of 843 exomes from epilepsy family trios identifies synonymous variants in known epilepsy genes, thus pinpointing risk factors of disease from non-coding sequence data. TraP outperforms leading methods in identifying non-coding variants that are pathogenic and is therefore a valuable tool for use in gene discovery and the interpretation of personal genomes.
Nutrient limitation determines the fitness of cheaters in bacterial siderophore cooperation
Authors: Sexton D. Joseph , Schuster Martin
Published: August 2017

Cooperative behaviors provide a collective benefit, but are considered costly for the individual. Here, we report that these costs vary dramatically in different contexts and have opposing effects on the selection for non-cooperating cheaters. We investigate a prominent example of bacterial cooperation, the secretion of the peptide siderophore pyoverdine by Pseudomonas aeruginosa, under different nutrient-limiting conditions. Using metabolic modeling, we show that pyoverdine incurs a fitness cost only when its building blocks carbon or nitrogen are growth-limiting and are diverted from cellular biomass production. We confirm this result experimentally with a continuous-culture approach. We show that pyoverdine non-producers (cheaters) enjoy a large fitness advantage in co-culture with producers (cooperators) and spread to high frequency when limited by carbon, but not when limited by phosphorus. The principle of nutrient-dependent fitness costs has implications for the stability of cooperation in pathogenic and non-pathogenic environments, in biotechnological applications, and beyond the microbial realm.
Absence of Grail promotes CD8+ T cell
anti-tumour activity
Authors: Haymaker Cara , Yang Yi , Wang Junmei , Zou Qiang , Sahoo Anupama , Alekseev Andrei , Singh Divyendu , Ritthipichai Krit , Hailemichael Yared , Hoang Oanh N. , Qin Hong , Schluns Kimberly S. , Wang Tiejun , Overwijk Willem W. , Sun Shao-Cong , Bernatchez Chantale , Kwak Larry W. , Neelapu Sattva S. , Nurieva Roza
Published: August 2017

T-cell tolerance is a major obstacle to successful cancer immunotherapy; thus, developing strategies to break immune tolerance is a high priority. Here we show that expression of the E3 ubiquitin ligase Grail is upregulated in CD8+ T cells that have infiltrated into transplanted lymphoma tumours, and Grail deficiency confers long-term tumour control. Importantly, therapeutic transfer of Grail-deficient CD8+ T cells is sufficient to repress established tumours. Mechanistically, loss of Grail enhances anti-tumour reactivity and functionality of CD8+ T cells. In addition, Grail-deficient CD8+ T cells have increased IL-21 receptor (IL-21R) expression and hyperresponsiveness to IL-21 signalling as Grail promotes IL-21R ubiquitination and degradation. Moreover, CD8+ T cells isolated from lymphoma patients express higher levels of Grail and lower levels of IL-21R, compared with CD8+ T cells from normal donors. Our data demonstrate that Grail is a crucial factor controlling CD8+ T-cell function and is a potential target to improve cytotoxic T-cell activity.
Serial processing of kinematic signals by cerebellar circuitry during voluntary whisking
Authors: Chen Susu , Augustine George J. , Chadderton Paul
Published: August 2017

Purkinje cells (PCs) in Crus 1 represent whisker movement via linear changes in firing rate, but the circuit mechanisms underlying this coding scheme are unknown. Here we examine the role of upstream inputs to PCs—excitatory granule cells (GCs) and inhibitory molecular layer interneurons—in processing of whisking signals. Patch clamp recordings in GCs reveal that movement is accompanied by changes in mossy fibre input rate that drive membrane potential depolarisation and high-frequency bursting activity at preferred whisker angles. Although individual GCs are narrowly tuned, GC populations provide linear excitatory drive across a wide range of movement. Molecular layer interneurons exhibit bidirectional firing rate changes during whisking, similar to PCs. Together, GC populations provide downstream PCs with linear representations of volitional movement, while inhibitory networks invert these signals. The exquisite sensitivity of neurons at each processing stage enables faithful propagation of kinematic representations through the cerebellum.
Inhomogeneous strain-induced half-metallicity in bent zigzag graphene nanoribbons
Authors: Zhang Dong-Bo , Wei Su-Huai
Published: August 2017

Realization of half-metallicity in low dimensional materials is a fundamental challenge for nano spintronics, which is a critical component for next-generation information technology. Using the method of generalized Bloch theorem, we show that an in-plane bending can induce inhomogeneous strains, which in turn lead to spin-splitting in zigzag graphene nanoribbons and results in the highly desired half-metallic state. Unlike the previously proposed scheme that requires unrealistically strong external electric fields, the obtained half-metallicity with sizeable half-metallic gap and high energetic stability of magnetic order of edge states requires only relatively low-level strain in the in-plane bending. Given the superior structural flexibility of graphene and the recent experimental advances in controllable synthesis of graphene nanoribbons, our design provides a hitherto most practical approach to the realization of half-metallicity in low dimensional systems. This work, thus paves a way towards the design of nanoscale spintronic devices through strain engineering.
The Gordon Research Seminar & Conference on Parkinson’s disease: state of the Science 200 years after James Parkinson’s essay on the Shaking Palsy
Authors: Greenamyre J. T. , De Miranda B. R. , Bucher M. L. , Singleton A. B. , Tansey M. G.
Published: August 2017

The first-ever Gordon Research Seminar on Parkinson’s disease was held in conjunction with the second-ever Gordon Research Conference on Parkinson’s disease at the Grand Summit Hotel at Sunday River in Newry, Maine, from June 24–30. The Gordon Research Seminar brought together graduate students and postdoctoral researchers to network, learn first-hand about life with Parkinson’s disease, listen to and present Parkinson’s disease science, and hear about a variety of relevant career options. The Gordon Research Conference began as the Gordon Research Seminar concluded and was attended by a broad, international mix of junior and senior scientists from academia and industry. It was organized into eight outstanding scientific sessions in which cutting edge science, much of it unpublished, was presented. Among attendees, there was universal praise for the content and organization of the meeting, and for its open and welcoming ambiance.
Lead and Chromium Adsorption from Water using L-Cysteine Functionalized Magnetite (Fe3O4) Nanoparticles
Authors: Bagbi Yana , Sarswat Ankur , Mohan Dinesh , Pandey Arvind , Solanki Pratima R.
Published: August 2017

L-Cysteine functionalized magnetite nanoparticles (L-Cyst-Fe3O4 NPs) were synthesized by chemical co-precipitation using Fe2+ and Fe3+ as iron precursors, sodium hydroxide as a base and L-Cysteine as functionalized agent. The structural and morphological studies were carried out using X-ray powder diffraction, transmission electron microscopy, dynamic light scattering, scanning electron microscopy and energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and UV-Vis spectrophotometric techniques. The zeta potential of bare Fe3O4 and functionalized L-Cyst-Fe3O4 NPs were +28 mV and −30.2 mV (pH 7.0), respectively. The positive surface charge changes to negative imply the presence of L-Cyst monolayer at particle interface. Band gap energy of 2.12 eV [bare Fe3O4NPs] and 1.4 eV [L-Cyst-Fe3O4 NPs] were obtained. Lead and chromium removal were investigated at different initial pHs, contact time, temperatures and adsorbate-adsorbent concentrations. Maximum Cr6+ and Pb2+ removal occurred at pH 2.0 and 6.0, respectively. Sorption dynamics data were best described by pseudo-second order rate equation. Pb2+ and Cr6+ sorption equilibrium data were best fitted to Langmuir equation. Langmuir adsorption capacities of 18.8 mg/g (Pb2+) and 34.5 mg/g (Cr6+) at 45 °C were obtained. Regeneration of exhausted L-Cyst-Fe3O4 NPs and recovery of Pb2+/Cr6+ were demonstrated using 0.01 M HNO3 and NaOH. L-Cyst-Fe3O4 NPs stability and reusability were also demonstrated.
Analysis of inflammatory cytokine and TLR expression levels in Type 2 Diabetes with complications
Authors: Gupta Saket , Maratha Ashwini , Siednienko Jakub , Natarajan Anandan , Gajanayake Thusitha , Hoashi Shu , Miggin Sinéad
Published: August 2017

The pathogenesis and complications of type 2 diabetes (T2DM) are closely linked with defective glucose metabolism, obesity, cardiovascular disease and an inability to mount an effective immune response to certain pathogenic organisms. Perturbations in key innate immune receptors known as Toll-like receptors (TLRs) and inflammatory mediators such as IL-6, TNFα and IL-1β have been linked with T2DM. Herein, we sought to establish whether patients with T2DM and underlying complications exhibit perturbations in cytokine and TLR expression. Serum cytokine and mRNA levels of cytokines/TLRs in monocytes (M) and neutrophils (N) were measured in a cohort of 112 diabetic patients: good glycaemic control without complications (GC), good glycaemic control with complications (GCC), poor glycaemic control without complications (PC) and poor glycaemic control with complications (PCC) and compared them with 34 non-diabetic volunteers (NGT). Serum cytokine levels were normal in all study participants. In the GC group, cytokine and TLR gene expression were enhanced compared to NGT. In contrast, suppressed cytokine and TLR gene expression were evident in PC, GCC & PCC groups when compared to the GC. In conclusion, whereas serum pro-inflammatory cytokine levels are unaltered in T2DM patients, differences in inflammatory gene profiles exist among the T2DM patient groups.
Quantifying the efficiency of Hydroxyapatite Mineralising Peptides
Authors: Plowright Robyn , Belton David J. , Kaplan David L. , Perry Carole C.
Published: August 2017

We present a non-destructive analytical calibration tool to allow quantitative assessment of individual calcium phosphates such as hydroxyapatite (HAP) from mixtures including brushite. Many experimental approaches are used to evaluate the mineralising capabilities of biomolecules including peptides. However, it is difficult to quantitatively compare the efficacy of peptides in the promotion of mineralisation when inseparable mixtures of different minerals are produced. To address this challenge, a series of hydroxyapatite and brushite mixtures were produced as a percent/weight (0–100%) from pure components and multiple (N = 10) XRD patterns were collected for each mixture. A linear relationship between the ratio of selected peak heights and the molar ratio was found. Using this method, the mineralising capabilities of three known hydroxyapatite binding peptides, CaP(S) STLPIPHEFSRE, CaP(V) VTKHLNQISQSY and CaP(H) SVSVGMKPSPRP, was compared. All three directed mineralisation towards hydroxyapatite in a peptide concentration dependent manner. CaP(V) was most effective at inducing hydroxyapatite formation at higher reagent levels (Ca2+ = 200 mM), as also seen with peptide-silk chimeric materials, whereas CaP(S) was most effective when lower concentrations of calcium (20 mM) and phosphate were used. The approach can be extended to investigate HAP mineralisation in the presence of any number of mineralisation promoters or inhibitors.
The Mechanical Representation of Temporal Delays
Authors: Leib Raz , Karniel Amir , Mussa-Ivaldi Ferdinando A.
Published: August 2017

When we knock on a door, we perceive the impact as a collection of simultaneous events, combining sound, sight, and tactile sensation. In reality, information from different modalities but from a single source is flowing inside the brain along different pathways, reaching processing centers at different times. Therefore, interpreting different sensory modalities which seem to occur simultaneously requires information processing that accounts for these different delays. As in a computer-based robotic system, does the brain use some explicit estimation of the time delay, to realign the sensory flows? Or does it compensate for temporal delays by representing them as changes in the body/environment mechanics? Using delayed-state or an approximation for delayed-state manipulations between visual and proprioceptive feedback during a tracking task, we show that tracking errors, grip forces, and learning curves are consistent with predictions of a representation that is based on approximation for delay, refuting an explicit delayed-state representation. Delayed-state representations are based on estimating the time elapsed between the movement commands and their observed consequences. In contrast, an approximation for delay representations result from estimating the instantaneous relation between the expected and observed motion variables, without explicit reference to time.
The anti-influenza M2e antibody response is promoted by XCR1 targeting in pig skin
Authors: Deloizy Charlotte , Fossum Even , Barnier-Quer Christophe , Urien Céline , Chrun Tiphany , Duval Audrey , Codjovi Maelle , Bouguyon Edwige , Maisonnasse Pauline , Hervé Pierre-Louis , Barc Céline , Boulesteix Olivier , Pezant Jérémy , Chevalier Christophe , Collin Nicolas , Dalod Marc , Bogen Bjarne , Bertho Nicolas , Schwartz-Cornil Isabelle
Published: August 2017

XCR1 is selectively expressed on a conventional dendritic cell subset, the cDC1 subset, through phylogenetically distant species. The outcome of antigen-targeting to XCR1 may therefore be similar across species, permitting the translation of results from experimental models to human and veterinary applications. Here we evaluated in pigs the immunogenicity of bivalent protein structures made of XCL1 fused to the external portion of the influenza virus M2 proton pump, which is conserved through strains and a candidate for universal influenza vaccines. Pigs represent a relevant target of such universal vaccines as pigs can be infected by swine, human and avian strains. We found that cDC1 were the only cell type labeled by XCR1-targeted mCherry upon intradermal injection in pig skin. XCR1-targeted M2e induced higher IgG responses in seronegative and seropositive pigs as compared to non-targeted M2e. The IgG response was less significantly enhanced by CpG than by XCR1 targeting, and CpG did not further increase the response elicited by XCR1 targeting. Monophosphoryl lipid A with neutral liposomes did not have significant effect. Thus altogether M2e-targeting to XCR1 shows promises for a trans-species universal influenza vaccine strategy, possibly avoiding the use of classical adjuvants.
Dextran-Catechin inhibits angiogenesis by disrupting copper homeostasis in endothelial cells
Authors: Yee Eugene M. H. , Brandl Miriam B. , Pasquier Eddy , Cirillo Giuseppe , Kimpton Kathleen , Kavallaris Maria , Kumar Naresh , Vittorio Orazio
Published: August 2017

Formation of blood vessels, or angiogenesis, is crucial to cancer progression. Thus, inhibiting angiogenesis can limit the growth and spread of tumors. The natural polyphenol catechin has moderate anti-tumor activity and interacts with copper, which is essential for angiogenesis. Catechin is easily metabolized in the body and this limits its clinical application. We have recently shown that conjugation of catechin with dextran (Dextran-Catechin) improves its serum stability, and exhibits potent anti-tumor activity against neuroblastoma by targeting copper homeostasis. Herein, we investigated the antiangiogenic activity of Dextran-Catechin and its mechanism. We found that Dextran-Catechin displayed potent antiangiogenic activity in vitro and in vivo. We demonstrated Dextran-Catechin generates reactive oxygen species which in turns disrupts copper homeostasis by depleting the copper importer CTR-1 and copper trafficking ATOX-1 protein. Mechanistically, we showed that disrupting copper homeostasis by knockdown of either CTR-1 or ATOX-1 protein can inhibit angiogenesis in endothelial cells. This data strongly suggests the Dextran-Catechin potent antiangiogenic activity is mediated by disrupting copper homeostasis. Thus, compounds such as Dextran-Catechin that affects both tumor growth and angiogenesis could lead the way for development of new drugs against high copper levels tumors.
The interplay of social group biases in social threat learning
Authors: Golkar Armita , Olsson Andreas
Published: August 2017

Learning from other individuals (e.g. social learning) is subjected to biases affecting whom to learn from. Consistent with research in animals, showing similarity-based learning biases and a general tendency to display pro-social responses to in-group individuals, we recently demonstrated that social learning of both fear and safety was enhanced when information was transmitted between same-race individuals. Here, we addressed how two different social group categories jointly affect the transmission of fears by investigating the interplay between racial and supporter group membership. We demonstrate that supporter group membership differentially influenced learning from a racial in-group vs. racial out-group individual. Thus, conditioned skin conductance responses in the same-race condition were significantly higher when fear was transmitted by an in-group (same team) vs. an out-group (rival team) individual, and were related to supporter team identification. However, supporter group membership did not influence learning from a racial out-group demonstrator, suggesting that the presence of an alternative alliance does not necessary reduce the influence of racial biases on social fear learning.
Chemical diplomacy in male tilapia: urinary signal increases sex hormone and decreases aggression
Authors: Saraiva João L. , Keller-Costa Tina , Hubbard Peter C. , Rato Ana , Canário Adelino V. M.
Published: August 2017

Androgens, namely 11-ketotestosterone (11KT), have a central role in male fish reproductive physiology and are thought to be involved in both aggression and social signalling. Aggressive encounters occur frequently in social species, and fights may cause energy depletion, injury and loss of social status. Signalling for social dominance and fighting ability in an agonistic context can minimize these costs. Here, we test the hypothesis of a ‘chemical diplomacy’ mechanism through urinary signals that avoids aggression and evokes an androgen response in receiver males of Mozambique tilapia (Oreochromis mossambicus). We show a decoupling between aggression and the androgen response; males fighting their mirror image experience an unresolved interaction and a severe drop in urinary 11KT. However, if concurrently exposed to dominant male urine, aggression drops but urinary 11KT levels remain high. Furthermore, 11KT increases in males exposed to dominant male urine in the absence of a visual stimulus. The use of a urinary signal to lower aggression may be an adaptive mechanism to resolve disputes and avoid the costs of fighting. As dominance is linked to nest building and mating with females, the 11KT response of subordinate males suggests chemical eavesdropping, possibly in preparation for parasitic fertilizations.
Interrelationship of rotavirus infection and Creatine Kinase-MB isoenzyme levels in children hospitalized with acute gastroenteritis in Guangzhou, China, 2012–2015
Authors: Zheng Jianbin , Zheng Haiqing , Gupta Ramit Kumar , Li Huixian , Shi Hui , Pan Liyan , Gong Sitang , Liang Huiying
Published: August 2017

Elevated levels of Creatine Kinase-MB (CK-MB) Isoenzyme are a common phenomenon among rotavirus (RV) diarrhea. However, few studies have addressed this issue using large sample size. In current study, 1,118 children (age <5 years) hospitalized with diarrhea in Guangzhou Women and Children’s Medical Center from 2012 to 2015 were finally included. Changing pattern of CK-MB and its relationship with RV-infection were analyzed and characterized. Multivariate linear regression models showed that RV-positive cases had a 28% rise in CK-MB compared to RV-negative cases (OR = 1.28, 95% CI: 1.15 to 1.41, P < 0.01) after controlling for age, gender, season of admission, and weight. The pattern of change showed that CK-MB level of RV-positive group started to rise immediately at the 1st day of diarrhea, reached the peak on days 2 to 4, declined during 4–9 days, and then reached a relatively stable level when compared to the RV-negative group. Mediation analyses showed that indirect effect of RV infection on the increase of CK-MB via Vesikari score was significant (β = 8.01, P < 0.01), but direct effect was not (β = 9.96, P = 0.12). Thus, elevated CK-MB value is a common finding in RV-infection and completely mediated by the severity of diarrhea. CK-MB monitoring may help to identify children with more severe viral infection.
Oral health-related quality of life in patients with stroke: a randomized clinical trial of oral hygiene care during outpatient rehabilitation
Authors: Dai Ruoxi , Lam Otto L. T. , Lo Edward C. M. , Li Leonard S. W. , McGrath Colman
Published: August 2017

This study was to evaluate the effectiveness of oral hygiene care in improving oral health- and health-related quality of life (OHRQoL and HRQoL) among patients receiving outpatient stroke rehabilitation. Subjects were randomized to: (1) a conventional oral hygiene care programme (COHCP) comprising a manual toothbrush, and oral hygiene instruction, or (2) an advanced oral hygiene care programme (AOHCP) comprising a powered toothbrush, 0.2% chlorhexidine mouthrinse, and oral hygiene instruction. The interventional period lasted for 3 months, followed by a 3-month observational period. HRQoL was assessed by SF-12, and OHRQoL was assessed by Oral Health Impact Profile-14 (OHIP-14), General Oral Health Assessment Index (GOHAI), and Oral Health Transitional Scale (OHTS). Participants in AOHCP group had significantly better OHRQoL at the end of clinical trial as assessed by OHTS (p < 0.01), and at the end of observational study as assessed by GOHAI (p < 0.05) than those in the COHCP. Participants in the AOHCP group had significantly better HRQoL as assessed by physical component summary score (PCS) the end of both 3 and 6 months (both p < 0.05). This study provided the evidence that the AOHCP was more effective than the COHCP within stroke rehabilitation in improving subjective health.
Fear of predation alters clone-specific performance in phloem-feeding prey
Authors: Khudr Mouhammad Shadi , Buzhdygan Oksana Y. , Petermann Jana S. , Wurst Susanne
Published: August 2017

Fear of predation has been shown to affect prey fitness and behaviour, however, to date little is known about the underlying genetics of responses to predator-associated risk. In an effort to fill this gap we exposed four naïve clones of green peach aphid (Myzus persicae), maintained on the model cropBrassica oleracea, to different types of cues from aphid lion (Chrysoperla carnea). The respective predation risks, we termedFear Factors, were either lethal (consumption by predator), or non-lethal (non-consumptive predator-associated cues: plant-tethered predator cadavers and homogenised shoot-sprayed or soil-infused blends of predator remains). Our results show that the non-lethal risk cues differentially impeded prey reproductive success that varied by clone, suggesting genotype-specific response to fear of predation. Furthermore, whether plants were perceived as being safe or risky influenced prey responses as avoidance behaviour in prey depended on clone type. Our findings highlight that intra-specific genetic variation underlies prey responses to consumptive and non-consumptive effects of predation. This allows selection to act on anti-predator responses to fear of predation that may ramify and influence higher trophic levels in model agroecosystems.
The roles of barriers, refugia, and chromosomal clines underlying diversification in Atlantic Forest social wasps
Authors: Menezes Rodolpho S. T. , Brady Seán G. , Carvalho Antônio F. , Del Lama Marco A. , Costa Marco A.
Published: August 2017

Phylogeographic studies have sought to explain the genetic imprints of historical climatic changes and geographic barriers within the Brazilian Atlantic Forest (AF) biota, and consequently two processes of diversification (refugia and barriers) have been proposed. Additionally, there is evidence that eustatic changes influenced the biogeographic history of the AF. Here we evaluate these contrasting diversification processes using two AF social wasp species – the mid-montane Synoeca cyanea and the lowland Synoeca aff. septentrionalis. We analyzed several sources of data including multilocus DNA sequence, climatic niche models and chromosomal features. We find support for idiosyncratic phylogeographic patterns between these wasps, involving different levels of population structure and genetic diversity, contrary suitable climatic conditions during the last glaciation, and contrasting historical movements along the AF. Our data indicate that neotectonics and refugia played distinct roles in shaping the genetic structure of these wasps. However, we argue that eustatic changes influenced the demographic expansion but not population structure in AF biota. Notably, these wasps exhibited chromosomal clines, involving chromosome number and decreasing of GC content, latitudinally oriented along the AF. Together, these results reinforce the need to consider individual organismal histories and indicate that barriers and refugia are significant factors in understanding AF evolution.
Anthocyanin concentration depends on the counterbalance between its synthesis and degradation in plum fruit at high temperature
Authors: Niu Junping , Zhang Guojing , Zhang Wenting , Goltsev Vasilij , Sun Shan , Wang Jinzheng , Li Pengmin , Ma Fengwang
Published: August 2017

Anthocyanin synthesis and degradation processes were analyzed at transcript, enzyme, and metabolite levels to clarify the effects of high temperature on the concentration of anthocyanin in plum fruit (Prunus salicina Lindl.). The transcript levels of PsPAL, PsCHS, and PsDFR decreased while those of PsANS and PsUFGT were similar at 35 °C compared with 20 °C. The activities of the enzymes encoded by these genes were all increased in fruits at 35 °C. The concentrations of anthocyanins were higher at 35 °C on day 5 but then decreased to lower values on day 9 compared with that at 20 °C. Furthermore, high temperature (35 °C) increased the concentration of hydrogen peroxide and the activity of class III peroxidase in the fruit. The concentration of procatechuic acid, a product of the reaction between anthocyanin and hydrogen peroxide, hardly changed at 20 °C but was significantly increased at 35 °C on day 9, indicating that anthocyanin was degraded by hydrogen peroxide, which was catalyzed by class III peroxidase. Based on mathematical modeling, it was estimated that more than 60–70% was enzymatically degraded on day 9 when the temperature increased from 20 °C to 35 °C. We conclude that at the high temperature, the anthocyanin content in plum fruit depend on the counterbalance between its synthesis and degradation.
Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation
Authors: Desai Harsh R. , Sivasubramaniyam Tharini , Revelo Xavier S. , Schroer Stephanie A. , Luk Cynthia T. , Rikkala Prashanth R. , Metherel Adam H. , Dodington David W. , Park Yoo Jin , Kim Min Jeong , Rapps Joshua A. , Besla Rickvinder , Robbins Clinton S. , Wagner Kay-Uwe , Bazinet Richard P. , Winer Daniel A. , Woo Minna
Published: August 2017

During obesity, macrophages can infiltrate metabolic tissues, and contribute to chronic low-grade inflammation, and mediate insulin resistance and diabetes. Recent studies have elucidated the metabolic role of JAK2, a key mediator downstream of various cytokines and growth factors. Our study addresses the essential role of macrophage JAK2 in the pathogenesis to obesity-associated inflammation and insulin resistance. During high-fat diet (HFD) feeding, macrophage-specific JAK2 knockout (M-JAK2−/−) mice gained less body weight compared to wildtype littermate control (M-JAK2+/+) mice and were protected from HFD-induced systemic insulin resistance. Histological analysis revealed smaller adipocytes and qPCR analysis showed upregulated expression of some adipogenesis markers in visceral adipose tissue (VAT) of HFD-fed M-JAK2−/−mice. There were decreased crown-like structures in VAT along with reduced mRNA expression of some macrophage markers and chemokines in liver and VAT of HFD-fed M-JAK2−/−mice. Peritoneal macrophages from M-JAK2−/−mice andJak2knockdown in macrophage cell line RAW 264.7 also showed lower levels of chemokine expression and reduced phosphorylated STAT3. However, leptin-dependent effects on augmenting chemokine expression in RAW 264.7 cells did not require JAK2. Collectively, our findings show that macrophage JAK2 deficiency improves systemic insulin sensitivity and reduces inflammation in VAT and liver in response to metabolic stress.
The Conserved Lysine-265 Allosterically Modulates Nucleotide- and Actin-binding Site Coupling in Myosin-2
Authors: Behrens Vincent A. , Münnich Stefan , Adler-Gunzelmann Georg , Thiel Claudia , Henn Arnon , Latham Sharissa L. , Taft Manuel H.
Published: August 2017

Myosin motor proteins convert chemical energy into force and movement through their interactions with nucleotide and filamentous actin (F-actin). The evolutionarily conserved lysine-265 (K265) of the myosin-2 motor from Dictyostelium discoideum (Dd) is proposed to be a key residue in an allosteric communication pathway that mediates actin-nucleotide coupling. To better understand the role of K265, point mutations were introduced within the Dd myosin-2 M765-2R framework, replacing this lysine with alanine (K265A), glutamic acid (K265E) or glutamine (K265Q), and the functional and kinetic properties of the resulting myosin motors were assessed. The alanine and glutamic acid substitutions reduced actin-activated ATPase activity, slowed the in vitro sliding velocity and attenuated the inhibitory potential of the allosteric myosin inhibitor pentabromopseudilin (PBP). However, glutamine substitution did not substantially change these parameters. Structural modelling suggests that K265 interacts with D590 and Q633 to establish a pivotal allosteric branching point. Based on our results, we propose: (1) that the K265-D590 interaction functions to reduce myosins basal ATPase activity in the absence of F-actin, and (2) that the dynamic formation of the K265-Q633 salt bridge upon actin cleft closure regulates the activation of product release by actin filaments.