bluuebunny/crossref_metadata_2025 huggingface dataset:
Microinsertions in PRKACA cause activation of the protein kinase A pathway in cardiac myxoma
Authors: Tseng I‐Ching , Huang Wei‐Ju , Jhuang Yu‐Ling , Chang Ya‐Yun , Hsu Hung‐Pin , Jeng Yung‐Ming
Published: March 2017

Cardiac myxoma is the most common cardiac tumour. Most lesions occur sporadically, but occasional lesions develop in patients with Carney complex, a syndrome characterized by cardiac myxoma, spotty pigmentation, and endocrine overactivity. Two‐thirds of patients with Carney complex harbour germline mutations in PRKAR1A, which encodes the type I regulatory subunit of protein kinase A (PKA). Most studies have not found a mutation in PRKAR1A in sporadic cardiac myxoma cases. Recent studies identified frequent mutations in PRKACA, which encodes the catalytic subunit of PKA, in cortisol‐secreting adrenocortical adenoma cases. To determine whether the PRKACA mutation is involved in the tumourigenesis of cardiac myxoma, we performed Sanger sequencing of 41 specimens of sporadic cardiac myxoma to test for the presence of mutations in the coding regions and intron–exon boundaries of PRKACA. Mutations were identified in four cases (9.7%). In contrast to the point mutations identified in adrenocortical adenoma, all mutations were in‐frame microinsertions of 18–33 bp clustered in exons 7 and 8. The mutated PRKACA proteins lost their ability to bind to PRKAR1A, and thereby lead to constitutive activation of the PKA pathway. Together with previous reports of PRKAR1A mutations in syndromic cardiac myxoma, our study demonstrates the importance of the PKA pathway in the tumourigenesis of cardiac myxoma. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Thermostamping of [0/90]n carbon/peek laminates: Influence of support configuration and demolding temperature on part consolidation
Authors: Benkaddour Abdelhaq , Lebrun Gilbert , Laberge‐Lebel Louis
Published: March 2017

This work presents experimental results on the thermostamping of carbon/PEEK cross‐ply laminates made of unidirectional prepregs. The first objective was to evaluate the effect of the supporting frame and laminate thickness on the consolidation quality of the final part. Based on the use of a square frame mounted with constant‐force springs clamps, three support configurations are compared: (i) clamp a polyimide film with the springs and use it to support the blank, (ii) support the blank with the constant‐force springs without polyimide film and (iii) support both the blank and a polyimide film with the springs. Using the best of these configurations (configurations ii and iii), the second objective was to push further the analysis and evaluate how demolding at different temperatures affects the part thickness distribution, the interlaminar shear strength and the cycle time of the process. Good consolidation qualities were obtained with configurations (ii) and (iii). However, the latter allows for more uniformity in the part thickness and higher shear strength when demolding at higher temperatures. It also allows a reduction of the molding cycle time considering the part can be demolded at a higher temperature (reduced cooling time). POLYM. COMPOS., 39:3341–3352, 2018. © 2017 Society of Plastics Engineers
Development of polymeric heat insulators based on emirati red shale filler: Thermal and physical properties
Authors: Abu‐Jdayil Basim , Mourad Abdel‐Hamid , Hassan Muzamil
Published: March 2017

This study reports the results of an experimental investigation on thermal and physical properties of composite materials made of unsaturated polyester (UPE) and Emirati red shale to be used as insulating materials. Stable composites with filler content ranging from 0 to 60 vol.% were prepared. The characterized properties of the UPE‐shale composites, namely; density, thermal conductivity, water retention, thermal stability, microstructure, and chemical resistance, showed promise for constructive applications as a thermal insulator. Up to filler content of 30 vol%, the thermal conductivity of the UPE‐shale composites did not exceed that of neat polymer and the water retention at room temperature was <0.2%. The effect of the main components in the filler (alumina and silica) on composite properties was detected at filler content >40 vol%, which led to increase the thermal conductivity with filler content. On the other hand, incorporating of shale into UPEs matrix improved its thermal stability. In addition, the UPE‐shale composites showed high resistance to acid and base impregnation. Increasing the shale content has improved clearly the composite resistance to alkaline medium. The potential for development in the field of energy saving and construction utilizing such cheap and abundant filler from natural resources seems to be very promising. Production of composite material with competitive thermal insulation properties utilizing cheap and abundant filler from natural resources seems to be very promising. POLYM. COMPOS., 39:E1463–E1473, 2018. © 2017 Society of Plastics Engineers
Study on structure and property relations of α‐iPP during uniaxial deformation via in situ synchrotron SAXS/WAXS and POM investigations
Authors: Shang Yingrui , Ning Puqing , Zhang Yao , Xue Feifei , Cai Ziwei , Li Jingqing , Ma Guiqiu , Song Jian , Wu Zhonghua , Jiang Shichun
Published: March 2017

Micro‐ and meso‐scale structure changes of α‐form isotactic polypropylene (α‐iPP) during uniaxial stretching is studied by time‐resolved synchrotron small‐angle X‐ray scattering (SAXS) and wide‐angle X‐ray scattering (WAXS). The structure/property relations are investigated at different temperatures, and the effects of isothermal crystallization are also studied with POM. The X‐ray scattering results show that the long period increased and the lamellar oriented along the stretching direction in the elastic deformation stage. The lamellar and crystals start destructing after yielding. And from it POM images it can be seen that with higher crystallization temperature the spherulites connected to form a crystalline network, on which the stress is mainly loaded. It turns out different environment temperatures affect mostly the amorphous domains. And samples exhibit different yielding mechanisms with different thermal histories. A hypothetical structural mechanism is proposed based to explain the observed relationship between the processing parameters, thermal history and the structure/property relations of α‐iPP. POLYM. ENG. SCI., 58:160–169, 2018. © 2017 Society of Plastics Engineers
The fluorescence intensities ratio is not a reliable parameter for evaluation of protein unfolding transitions
Authors: Žoldák Gabriel , Jancura Daniel , Sedlák Erik
Published: March 2017

Monitoring the fluorescence of proteins, particularly the fluorescence of intrinsic tryptophan residues, is a popular method often used in the analysis of unfolding transitions (induced by temperature, chemical denaturant, and pH) in proteins. The tryptophan fluorescence provides several suitable parameters, such as steady‐state fluorescence intensity, apparent quantum yield, mean fluorescence lifetime, position of emission maximum that are often utilized for the observation of the conformational/unfolding transitions of proteins. In addition, the fluorescence intensities ratio at different wavelengths (usually at 330 nm and 350 nm) is becoming an increasingly popular parameter for the evaluation of thermal transitions. We show that, under certain conditions, the use of this parameter for the analysis of unfolding transitions leads to the incorrect determination of thermodynamic parameters characterizing unfolding transitions in proteins (e.g., melting temperature) and, hence, can compromise the hit identification during high‐throughput drug screening campaigns.
Design, synthesis, antiviral bioactivity and three‐dimensional quantitative structure–activity relationship study of novel ferulic acid ester derivatives containing quinazoline moiety
Authors: Wu Zengxue , Zhang Jian , Chen Jixiang , Pan Jianke , Zhao Lei , Liu Dengyue , Zhang Awei , Chen Jin , Hu Deyu , Song Baoan
Published: March 2017

BACKGROUND

Ferulic acid and quinazoline derivatives possess good antiviral activities. In order to develop novel compounds with high antiviral activities, a series of ferulic acid ester derivatives containing quinazoline were synthesized and evaluated for their antiviral activities.

RESULTS

Bioassays indicated that some of the compounds exhibited good antiviral activities in vivo against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). One of the compounds demonstrated significant curative and protective activities against TMV and CMV, with EC50 values of 162.14, 114.61 and 255.49, 138.81 mg L−1, respectively, better than those of ningnanmycin (324.51, 168.84 and 373.88, 272.70 mg L−1). The values of q2 and r2 for comparative molecular field analysis and comparative molecular similarity index analysis in the TMV (0.508, 0.663 and 0.992, 0.930) and CMV (0.530, 0.626 and 0.997, 0.981) models presented good predictive abilities.

CONCLUSION

Some of the title compounds demonstrated good antiviral activities. Three‐dimensional quantitative structure–activity relationship models revealed that the antiviral activities depend on steric and electrostatic properties. These results could provide significant structural insights for the design of highly active ferulic acid derivatives. © 2017 Society of Chemical Industry
Finite‐time sliding mode observer for uncertain nonlinear systems based on a tunable algebraic solver
Authors: López Esteban , Botero Héctor
Published: March 2017

In this paper, a finite‐time sliding mode observer for nonlinear systems with unknown inputs is proposed. The observer is based on a method for the solution of time‐varying algebraic equations. This algebraic solver is shown to converge in finite time by means of Lyapunov analysis; furthermore, a way to tune it so that it converges after a user‐defined amount of time is presented. Through the use of this technique and sliding mode differentiators, the state variables and unknown inputs of a class of nonlinear systems, which do not need to be affine in the inputs, can be estimated without the explicit use of state transformations. Both the algebraic solver and the proposed observer are illustrated through simulation examples. Copyright © 2017 John Wiley & Sons, Ltd.
Theoretical Studies for Switching Regioselectivity in Ruthenium Hydride‐Catalyzed Alkyne Hydroacylation
Authors: Wang Fen , Meng Qingxi
Published: March 2017

Density functional theory (DFT) was used to elucidate and explore ruthenium hydride‐catalyzed intermolecular pent‐2‐yne hydroacylation with three phosphine ligands (PMe3, PPh3, ferrocene‐based Josiphos L3). Ruthenium‐PMe3‐catalyzed intermolecular pent‐2‐yne hydroacylation had five plausible pathways producing five possible products (β,γ‐unsaturated ketones p1, p2, p3, and α,β‐unsaturated ketones p4, p5), and the α‐Et‐β,γ‐unsaturated ketone p1 was predicted theoretically to be dominant. Three steps (hydrogen migration, nucleophilic reaction, β‐hydrogen elimination) were the rate‐determining step for this pathway affording α‐Et‐β,γ‐unsaturated ketone p1. In ruthenium‐PPh3‐catalyzed pent‐2‐yne hydroacylation, the rate‐determining step was the β‐hydrogen elimination. In ruthenium‐L3‐catalyzed pent‐2‐yne hydroacylation, the rate‐determining step was also the β‐hydrogen elimination. Furthermore, the similarities and differences of three phosphine ligands were studied and indicated. All results were consistent with Dong's experiments.
Interaction Behavior between Active Hydrogen Bond Donor‐Acceptors as a Binding Decoration for Anion Recognition: Experimental Observation and Theoretical Validation
Authors: Karar Monaj , Paul Suvendu , Mallick Arabinda , Majumdar Tapas
Published: March 2017

Interactions of Harmine (HM), as hydrogen bond donor with different anions as hydrogen bond acceptors were studied using spectroscopic and computational techniques. Significant gradual changes in absorption and emission spectra were observed upon addition of fluoride anions with selectivity. Wide‐ranging theoretical calculations in association with the 1H NMR titration in CDCl3 medium were performed to establish the binding decoration of HM with fluoride ion. Interaction energies, bond length variation, NBO charge transfer, NMR response, MEP 3D surface & 2D contour plot, UV‐Vis spectral simulation, HOMO‐LUMO energy gaps and potential energy curves (PECs) were calculated theoretically employing DFT method for ground state (S0) and TD‐DFT method for first singlet excited electronic state (S1) in ACN. Calculations revealed the proton transfer as ESPT mechanism [extent of proton transfer in S0 (58 %) and S1 (87 %)] behind the molecular interaction and spectral responses. We believe such a fluoride selective sensor like HM may find application to detect and control fluoride content in different commodity products.
Rough-wall turbulent boundary layers with constant skin friction
Authors: Sridhar A. , Pullin D. I. , Cheng W.
Published: March 2017

A semi-empirical model is presented that describes the development of a fully developed turbulent boundary layer in the presence of surface roughness with length scale$k_{s}$that varies with streamwise distance$x$. Interest is centred on flows for which all terms of the von Kármán integral relation, including the ratio of outer velocity to friction velocity$U_{\infty }^{+}\equiv U_{\infty }/u_{\unicode[STIX]{x1D70F}}$, are streamwise constant. For$Re_{x}$assumed large, use is made of a simple log-wake model of the local turbulent mean-velocity profile that contains a standard mean-velocity correction for the asymptotic fully rough regime and with assumed constant parameter values. It is then shown that, for a general power-law external velocity variation$U_{\infty }\sim x^{m}$, all measures of the boundary-layer thickness must be proportional to$x$and that the surface sand-grain roughness scale variation must be the linear form$k_{s}(x)=\unicode[STIX]{x1D6FC}x$, where$x$is the distance from the boundary layer of zero thickness and$\unicode[STIX]{x1D6FC}$is a dimensionless constant. This is shown to give a two-parameter$(m,\unicode[STIX]{x1D6FC})$family of solutions, for which$U_{\infty }^{+}$(or equivalently$C_{f}$) and boundary-layer thicknesses can be simply calculated. These correspond to perfectly self-similar boundary-layer growth in the streamwise direction with similarity variable$z/(\unicode[STIX]{x1D6FC}x)$, where$z$is the wall-normal coordinate. Results from this model over a range of$\unicode[STIX]{x1D6FC}$are discussed for several cases, including the zero-pressure-gradient ($m=0$) and sink-flow ($m=-1$) boundary layers. Trends observed in the model are supported by wall-modelled large-eddy simulation of the zero-pressure-gradient case for$Re_{x}$in the range$10^{8}{-}10^{10}$and for four values of$\unicode[STIX]{x1D6FC}$. Linear streamwise growth of the displacement, momentum and nominal boundary-layer thicknesses is confirmed, while, for each$\unicode[STIX]{x1D6FC}$, the mean-velocity profiles and streamwise turbulent variances are found to collapse reasonably well onto$z/(\unicode[STIX]{x1D6FC}x)$. For given$\unicode[STIX]{x1D6FC}$, calculations of$U_{\infty }^{+}$obtained from large-eddy simulations are streamwise constant and independent of$Re_{x}$when this is large. The present results suggest that, in the sense that$U_{\infty }^{+}(\unicode[STIX]{x1D6FC},m)$is constant, these flows can be interpreted as the fully rough limit for boundary layers in the presence of small-scale linear roughness.
I am the Ocean – arts and sciences to move from ocean literacy to passion for the ocean
Authors: Dupont Sam
Published: March 2017

Recent events in world politics demonstrate that a part of society has lost faith in their institutions. The importance of facts and evidence in citizens’ decision making is weakened by opinions and belief systems. This post-fact or alternate facts era is a new challenge in the field of science communication as we urgently need to tackle global environmental challenges. Not only do scientists need to better communicate their work, they also need to explore alternative ways of transferring knowledge to help citizens reconnect with nature and actively take responsible decisions to protect it. The activity ‘I am the Ocean’ has been developed by an artist and a scientist with the goal to help students understand, connect and be equipped to take actions on marine global changes. The activity was a mix of field trips, open discussions and sensory immersion. It illustrates how art and metaphors can add an emotional and physical dimension to science communication, allowing a better understanding of otherwise invisible threats, and move from knowledge to passion.
Trajectories of ageing well among older Australians: a 16-year longitudinal study
Authors: BROWNING COLETTE J. , ENTICOTT JOANNE C. , THOMAS SHANE A. , KENDIG HAL
Published: March 2017

In this study we used individual differences concepts and analyses to examine whether older people achieve different ageing-well states universally or whether there are identifiable key groups that achieve them to different extents. The data used in the modelling were from a prospective 16-year longitudinal study of 1,000 older Australians. We examined predictors of trajectories for ageing well using self-rated health, psychological wellbeing and independence in daily living as joint indicators of ageing well in people aged over 65 years at baseline. We used group-trajectory modelling and multivariate regression to identify characteristics predicting ‘ageing well’. The results showed three distinct and sizeable ageing trajectory groups: (a) ‘stable-good ageing well’ (classified as ageing well in all longitudinal study waves; which was achieved by 30.2% of women and 28.0% of men); (b) ‘initially ageing well then deteriorating’ (50.5% women and 47.6% men); and (c) ‘stable-poor’ (not ageing well in any wave; 19.3% women and 24.4% men). Significant gender differences were found in membership in different ageing-well states. In the stable-poor groups there were 103/533 females which was significantly lower than 114/467 men (z-statistic = −2.6, p = 0.005); women had a ‘zero’ probability of progressing to a better ageing-well classification in later years, whilst males had a one-in-five probability of actually improving. Robust final state outcome predictors at baseline were lower age and fewer medical conditions for both genders; restful sleep and Australian-born for women; and good nutrition, decreased strain, non-smoker and good social support for men. These results support that ageing-well trajectories are influenced by modifiable factors. Findings will assist better targeting of health-promoting activities for older people.
Sharp-interface formation during lithium intercalation into silicon
Authors: MECA E. , MÜNCH A. , WAGNER B.
Published: March 2017

In this study, we present a phase-field model that describes the process of intercalation of Li ions into a layer of an amorphous solid such as amorphous silicon (a-Si). The governing equations couple a viscous Cahn–Hilliard-Reaction model with elasticity in the framework of the Cahn–Larché system. We discuss the parameter settings and flux conditions at the free boundary that lead to the formation of phase boundaries having a sharp gradient in lithium ion concentration between the initial state of the solid layer and the intercalated region. We carry out a matched asymptotic analysis to derive the corresponding sharp-interface model that also takes into account the dynamics of triple points where the sharp interface intersects the free boundary of the Si layer. We numerically compare the interface motion predicted by the sharp-interface model with the long-time dynamics of the phase-field model.
Frugivory and seed dispersal effectiveness in twoMiconia(Melastomataceae) species from ferruginouscampo rupestre
Authors: Santos Alessandra M. O. , Jacobi Claudia M. , Silveira Fernando A. O.
Published: March 2017

Seed dispersal effectiveness (SDE) is a useful framework to explore the evolutionary and ecological consequences of seed dispersal to plant fitness. However, SDE is poorly studied in tropical open grasslands. Here, we studied both quantitative and qualitative components of SDE in two species ofMiconia(Melastomataceae) from ferruginouscampo rupestre, a vegetation highly threatened by mining activities. We determined fruit traits and fruit availability and found that fruits of both species are produced in times of resource scarcity at the study site. Based on the number of visits and the number of fruits removed per visit, we calculated the quantitative component of SDE for both species. Finally, we explored the qualitative component of SDE by means of a controlled experiment that simulated the effects of gut passage on seed germination. Bird species differed strongly in the quantitative component of SDE. Gut passage did not affect germination compared with hand-extracted seeds, except for a minor negative effect on germination time inM. pepericarpa.However, seeds within intact fruits showed lower germination percentages compared with hand-extracted seeds. Our data indicate thatMiconiaspecies from ferruginouscampo rupestreare visited by a diverse assemblage of generalist birds that differ in quantitative, but not qualitative, seed dispersal effectiveness. We argue that plantingMiconiaspecies can overcome seed limitation in degraded areas and thus assist ecological restoration after mining abandonment.
Thomas Jefferson, Nature's God, and the Theological Foundations of Natural-Rights Republicanism
Authors: Cooper Kody W. , Dyer Justin Buckley
Published: March 2017

While the role of theology in Jefferson's political thought and its implications for how we should understand the role of “Nature's God” in grounding natural-rights republicanism are topics of ongoing scholarly interest, scholars have missed important continuities between Jefferson's natural-law theory and that of classical, theistic natural-law. Many scholars who have considered Jefferson in this light have emphasized Jefferson's discontinuity and even subversion of that tradition. In critical dialogue with this vein of scholarship, we argue that Jefferson espouses a creational metaphysics and a natural-law theory of morality that has surprising continuities with classical natural-law. We seek to shed new light on Jefferson's theory of the moral sense and his the earth belongs to the living principle, which we contend encapsulates his theistic understanding of equality and property.
Translation in astrocyte distal processes sets molecular heterogeneity at the gliovascular interface
Authors: Boulay Anne- Cécile , Saubaméa Bruno , Adam Nicolas , Chasseigneaux Stéphanie , Mazaré Noémie , Gilbert Alice , Bahin Mathieu , Bastianelli Leïla , Blugeon Corinne , Perrin Sandrine , Pouch Juliette , Ducos Bertrand , Le Crom Stéphane , Genovesio Auguste , Chrétien Fabrice , Declèves Xavier , Laplanche Jean-Louis , Cohen-Salmon Martine
Published: March 2017

Astrocytes send out long processes that are terminated by endfeet at the vascular surface and regulate vascular functions as well as homeostasis at the vascular interface. To date, the astroglial mechanisms underlying these functions have been poorly addressed. Here we demonstrate that a subset of messenger RNAs is distributed in astrocyte endfeet. We identified, among this transcriptome, a pool of messenger RNAs bound to ribosomes, the endfeetome, that primarily encodes for secreted and membrane proteins. We detected nascent protein synthesis in astrocyte endfeet. Finally, we determined the presence of smooth and rough endoplasmic reticulum and the Golgi apparatus in astrocyte perivascular processes and endfeet, suggesting for local maturation of membrane and secreted proteins. These results demonstrate for the first time that protein synthesis occurs in astrocyte perivascular distal processes that may sustain their structural and functional polarization at the vascular interface.
Device errors in asthma and COPD: systematic literature review and meta-analysis
Authors: Chrystyn Henry , van der Palen Job , Sharma Raj , Barnes Neil , Delafont Bruno , Mahajan Anadi , Thomas Mike
Published: March 2017

Inhaler device errors are common and may impact the effectiveness of the delivered drug. There is a paucity of up-to-date systematic reviews (SRs) or meta-analyses (MAs) of device errors in asthma and chronic obstructive pulmonary disease (COPD) patients. This SR and MA provides an estimate of overall error rates (both critical and non-critical) by device type and evaluates factors associated with inhaler misuse. The following databases from inception to July 23, 2014 (Embase®, MEDLINE®, MEDLINE® In-Process and CENTRAL) were searched, using predefined search terms. Studies in adult males and females with asthma or COPD, reporting at least one overall or critical error, using metered dose inhalers and dry powder inhalers were included. Random-effect MAs were performed to estimate device error rates and to compare pairs of devices. Overall and critical error rates were high across all devices, ranging from 50–100% and 14–92%, respectively. However, between-study heterogeneity was also generally >90% (I-squared statistic), indicating large variability between studies. A trend towards higher error rates with assessments comprising a larger number of steps was observed; however no consistent pattern was identified. This SR and MA highlights the relatively limited body of evidence assessing device errors and the lack of standardised checklists. There is currently insufficient evidence to determine differences in error rates between different inhaler devices and their impact on clinical outcomes. A key step in improving our knowledge on this topic would be the development of standardised checklists for each device.
Modeling Nosocomial Infections of Methicillin-Resistant Staphylococcus aureus with Environment Contamination*
Authors: Wang Lei , Ruan Shigui
Published: March 2017

In this work, we investigate the role of environmental contamination on the clinical epidemiology of antibiotic-resistant bacteria in hospitals. Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium that causes infections in different parts of the body. It is tougher to treat than most strains of Staphylococcus aureus or staph, because it is resistant to some commonly used antibiotics. Both deterministic and stochastic models are constructed to describe the transmission characteristics of MRSA in hospital setting. The deterministic epidemic model includes five compartments: colonized and uncolonized patients, contaminated and uncontaminated health care workers (HCWs), and bacterial load in environment. The basic reproduction number R0 is calculated, and its numerical and sensitivity analysis has been performed to study the asymptotic behavior of the model, and to help identify factors responsible for observed patterns of infections. A stochastic epidemic model with stochastic simulations is also presented to supply a comprehensive analysis of its behavior. Data collected from Beijing Tongren Hospital will be used in the numerical simulations of our model. The results can be used to provide theoretical guidance for designing efficient control measures, such as increasing the hand hygiene compliance of HCWs and disinfection rate of environment, and decreasing the transmission rate between environment and patients and HCWs.
Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction
Authors: Rodriguez-Nunez Ivan , Caluag Tiffany , Kirby Kori , Rudick Charles N. , Dziarski Roman , Gupta Dipika
Published: March 2017

Genetics plays a central role in susceptibility to obesity and metabolic diseases. BALB/c mice are known to be resistant to high fat diet (HFD)-induced obesity, however the genetic cause remains unknown. We report that deletion of the innate immunity antibacterial gene Nod2 abolishes this resistance, as Nod2−/− BALB/c mice developed HFD-dependent obesity and hallmark features of metabolic syndrome. Nod2−/− HFD mice developed hyperlipidemia, hyperglycemia, glucose intolerance, increased adiposity, and steatosis, with large lipid droplets in their hepatocytes. These changes were accompanied by increased expression of immune genes in adipose tissue and differential expression of genes for lipid metabolism, signaling, stress, transport, cell cycle, and development in both adipose tissue and liver. Nod2−/− HFD mice exhibited changes in the composition of the gut microbiota and long-term treatment with antibiotics abolished diet-dependent weight gain in Nod2−/− mice, but not in wild type mice. Furthermore, microbiota from Nod2−/− HFD mice transferred sensitivity to weight gain, steatosis, and hyperglycemia to wild type germ free mice. In summary, we have identified a novel role for Nod2 in obesity and demonstrate that Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction.
Circulating Tumor DNA Mutation Profiling by Targeted Next Generation Sequencing Provides Guidance for Personalized Treatments in Multiple Cancer Types
Authors: Shu Yongqian , Wu Xue , Tong Xiaoling , Wang Xiaonan , Chang Zhili , Mao Yu , Chen Xiaofeng , Sun Jing , Wang Zhenxin , Hong Zhuan , Zhu Liangjun , Zhu Chunrong , Chen Jun , Liang Ying , Shao Huawu , Shao Yang W.
Published: March 2017

Cancer is a disease of complex genetic alterations, and comprehensive genetic diagnosis is beneficial to match each patient to appropriate therapy. However, acquisition of representative tumor samples is invasive and sometimes impossible. Circulating tumor DNA (ctDNA) is a promising tool to use as a non-invasive biomarker for cancer mutation profiling. Here we implemented targeted next generation sequencing (NGS) with a customized gene panel of 382 cancer-relevant genes on 605 ctDNA samples in multiple cancer types. Overall, tumor-specific mutations were identified in 87% of ctDNA samples, with mutation spectra highly concordant with their matched tumor tissues. 71% of patients had at least one clinically-actionable mutation, 76% of which have suggested drugs approved or in clinical trials. In particular, our study reveals a unique mutation spectrum in Chinese lung cancer patients which could be used to guide treatment decisions and monitor drug-resistant mutations. Taken together, our study demonstrated the feasibility of clinically-useful targeted NGS-based ctDNA mutation profiling to guide treatment decisions in cancer.
Thermal stratification drives movement of a coastal apex predator
Authors: Aspillaga Eneko , Bartumeus Frederic , Starr Richard M. , López-Sanz Àngel , Linares Cristina , Díaz David , Garrabou Joaquim , Zabala Mikel , Hereu Bernat
Published: March 2017

A characterization of the thermal ecology of fishes is needed to better understand changes in ecosystems and species distributions arising from global warming. The movement of wild animals during changing environmental conditions provides essential information to help predict the future thermal response of large marine predators. We used acoustic telemetry to monitor the vertical movement activity of the common dentex (Dentex dentex), a Mediterranean coastal predator, in relation to the oscillations of the seasonal thermocline during two summer periods in the Medes Islands marine reserve (NW Mediterranean Sea). During the summer stratification period, the common dentex presented a clear preference for the warm suprathermoclinal layer, and adjusted their vertical movements following the depth changes of the thermocline. The same preference was also observed during the night, when fish were less active. Due to this behaviour, we hypothesize that inter-annual thermal oscillations and the predicted lengthening of summer conditions will have a significant positive impact on the metabolic efficiency, activity levels, and population dynamics of this species, particularly in its northern limit of distribution. These changes in the dynamics of an ecosystem’s keystone predator might cascade down to lower trophic levels, potentially re-defining the coastal fish communities of the future.
Hydrocortisone-induced parkin prevents dopaminergic cell death via CREB pathway in Parkinson’s disease model
Authors: Ham Sangwoo , Lee Yun-Il , Jo Minkyung , Kim Hyojung , Kang Hojin , Jo Areum , Lee Gum Hwa , Mo Yun Jeong , Park Sang Chul , Lee Yun Song , Shin Joo-Ho , Lee Yunjong
Published: March 2017

Dysfunctional parkin due to mutations or post-translational modifications contributes to dopaminergic neurodegeneration in Parkinson’s disease (PD). Overexpression of parkin provides protection against cellular stresses and prevents dopamine cell loss in several PD animal models. Here we performed an unbiased high-throughput luciferase screening to identify chemicals that can increase parkin expression. Among promising parkin inducers, hydrocortisone possessed the most favorable profiles including parkin induction ability, cell protection ability, and physicochemical property of absorption, distribution, metabolism, and excretion (ADME) without inducing endoplasmic reticulum stress. We found that hydrocortisone-induced parkin expression was accountable for cell protection against oxidative stress. Hydrocortisone-activated parkin expression was mediated by CREB pathway since gRNA to CREB abolished hydrocortisone’s ability to induce parkin. Finally, hydrocortisone treatment in mice increased brain parkin levels and prevented 6-hydroxy dopamine induced dopamine cell loss when assessed at 4 days after the toxin’s injection. Our results showed that hydrocortisone could stimulate parkin expression via CREB pathway and the induced parkin expression was accountable for its neuroprotective effect. Since glucocorticoid is a physiological hormone, maintaining optimal levels of glucocorticoid might be a potential therapeutic or preventive strategy for Parkinson’s disease.
Analyzing Single Molecule Localization Microscopy Data Using Cubic Splines
Authors: Babcock Hazen P. , Zhuang Xiaowei
Published: March 2017

The resolution of super-resolution microscopy based on single molecule localization is in part determined by the accuracy of the localization algorithm. In most published approaches to date this localization is done by fitting an analytical function that approximates the point spread function (PSF) of the microscope. However, particularly for localization in 3D, analytical functions such as a Gaussian, which are computationally inexpensive, may not accurately capture the PSF shape leading to reduced fitting accuracy. On the other hand, analytical functions that can accurately capture the PSF shape, such as those based on pupil functions, can be computationally expensive. Here we investigate the use of cubic splines as an alternative fitting approach. We demonstrate that cubic splines can capture the shape of any PSF with high accuracy and that they can be used for fitting the PSF with only a 2–3x increase in computation time as compared to Gaussian fitting. We provide an open-source software package that measures the PSF of any microscope and uses the measured PSF to perform 3D single molecule localization microscopy analysis with reasonable accuracy and speed.
Oral administration of Lactobacillus gasseri SBT2055 is effective in preventing Porphyromonas gingivalis-accelerated periodontal disease
Authors: Kobayashi R. , Kobayashi T. , Sakai F. , Hosoya T. , Yamamoto M. , Kurita-Ochiai T.
Published: March 2017

Probiotics have been used to treat gastrointestinal disorders. However, the effect of orally intubated probiotics on oral disease remains unclear. We assessed the potential of oral administration of Lactobacillus gasseri SBT2055 (LG2055) for Porphyromonas gingivalis infection. LG2055 treatment significantly reduced alveolar bone loss, detachment and disorganization of the periodontal ligament, and bacterial colonization by subsequent P. gingivalis challenge. Furthermore, the expression and secretion of TNF-α and IL-6 in gingival tissue was significantly decreased in LG2055-administered mice after bacterial infection. Conversely, mouse β-defensin-14 (mBD-14) mRNA and its peptide products were significantly increased in distant mucosal components as well as the intestinal tract to which LG2055 was introduced. Moreover, IL-1β and TNF-α production from THP-1 monocytes stimulated with P. gingivalis antigen was significantly reduced by the addition of human β-defensin-3. These results suggest that gastrically administered LG2055 can enhance immunoregulation followed by periodontitis prevention in oral mucosa via the gut immune system; i.e., the possibility of homing in innate immunity.
Aseismic transient during the 2010–2014 seismic swarm: evidence for longer recurrence of M ≥ 6.5 earthquakes in the Pollino gap (Southern Italy)?
Authors: Cheloni Daniele , D’Agostino Nicola , Selvaggi Giulio , Avallone Antonio , Fornaro Gianfranco , Giuliani Roberta , Reale Diego , Sansosti Eugenio , Tizzani Pietro
Published: March 2017

In actively deforming regions, crustal deformation is accommodated by earthquakes and through a variety of transient aseismic phenomena. Here, we study the 2010–2014 Pollino (Southern Italy) swarm sequence (main shock M
W
5.1) located within the Pollino seismic gap, by analysing the surface deformation derived from Global Positioning System and Synthetic Aperture Radar data. Inversions of geodetic time series show that a transient slip, with the same mechanism of the main shock, started about 3–4 months before the main shock and lasted almost one year, evolving through time with acceleration phases that correlate with the rate of seismicity. The moment released by the transient slip is equivalent to M
W
5.5, significantly larger than the seismic moment release revealing therefore that a significant fraction of the overall deformation is released aseismically. Our findings suggest that crustal deformation in the Pollino gap is accommodated by infrequent “large” earthquakes (M
W
 ≥ 6.5) and by aseismic episodes releasing a significant fraction of the accrued strain. Lower strain rates, relative to the adjacent Southern Apennines, and a mixed seismic/aseismic strain release are in favour of a longer recurrence for large magnitude earthquakes in the Pollino gap.
Microbial Functional Capacity Is Preserved Within Engineered Soil Formulations Used In Mine Site Restoration
Authors: Kumaresan Deepak , Cross Adam T , Moreira-Grez Benjamin , Kariman Khalil , Nevill Paul , Stevens Jason , Allcock Richard J N , O’Donnell Anthony G , Dixon Kingsley W , Whiteley Andrew S
Published: March 2017

Mining of mineral resources produces substantial volumes of crushed rock based wastes that are characterised by poor physical structure and hydrology, unstable geochemistry and potentially toxic chemical conditions. Recycling of these substrates is desirable and can be achieved by blending waste with native soil to form a ‘novel substrate’ which may be used in future landscape restoration. However, these post-mining substrate based ‘soils’ are likely to contain significant abiotic constraints for both plant and microbial growth. Effective use of these novel substrates for ecosystem restoration will depend on the efficacy of stored topsoil as a potential microbial inoculum as well as the subsequent generation of key microbial soil functions originally apparent in local pristine sites. Here, using both marker gene and shotgun metagenome sequencing, we show that topsoil storage and the blending of soil and waste substrates to form planting substrates gives rise to variable bacterial and archaeal phylogenetic composition but a high degree of metabolic conservation at the community metagenome level. Our data indicates that whilst low phylogenetic conservation is apparent across substrate blends we observe high functional redundancy in relation to key soil microbial pathways, allowing the potential for functional recovery of key belowground pathways under targeted management.
Single cell imaging and quantification of TDP-43 and α-synuclein intercellular propagation
Authors: Peled Sivan , Sade Dorin , Bram Yaron , Porat Ziv , Kreiser Topaz , Mimouni Michael , Lichtenstein Alexandra , Segal Daniel , Gazit Ehud
Published: March 2017

The intercellular spreading of protein assemblies is a major factor in the progression of neurodegenerative disorders. The quantitative study and visualization of cell-to-cell propagation using tagged-proteins is challenging due to the steric effect of relatively large fluorescence tags and the risk of ‘false positive’ identification when analyzing these rare transmission events. Here, we established a cell culture model to characterize the cell-to-cell transmission of TAR DNA-binding protein and α-synuclein, involved in amyotrophic lateral sclerosis and Parkinson’s disease, respectively, using the small nine amino acid influenza hemagglutinin tag. The novel use of single cell resolution imaging flow cytometry allowed the visualization and quantification of all individual transmission events. Cell-level analysis of these events indicated that the degree of transfer is lower than previously reported based on conventional flow cytometry. Furthermore, our analysis can exclude ‘false positive’ events of cellular overlap and extracellular debris attachment. The results were corroborated by high-resolution confocal microscopy mapping of protein localization.
Jasmonic acid-related resistance in tomato mediates interactions between whitefly and whitefly-transmitted virus
Authors: Sun Yan-Chun , Pan Li-Long , Ying Feng-Ze , Li Ping , Wang Xiao-Wei , Liu Shu-Sheng
Published: March 2017

The indirect interactions between insect vectors, such as whiteflies, and the viruses they transmit, such as begomoviruses, via host plants may produce a range of outcome depending on the species/strain of each of the three organisms involved, and the mechanisms underlying the variations are not well understood. Here, we observed the performance of whiteflies on three types of tomato, which vary in level of jasmonic acid (JA)-related resistance and were either uninfected or infected by a begomovirus, to investigate the role of JA-related resistance in mediating whitefly-begomovirus interactions. Compared to the performance of whiteflies on plants of the wild type, the performance was elevated on plants deficient in JA-related resistance but reduced on plants with a high level of JA-related resistance. Further, on plants with a high level of JA-related resistance, the whitefly performed better on virus-infected than on uninfected plants; however, on tomato plants deficient in JA-related resistance, whitefly performance was less affected by the virus-infection of plants. Additionally, the expression of the JA-regulated defense gene PI-II in tomato plants was repressed by virus infection. These findings suggest that JA-related resistance plays an important role in the tripartite interactions between whitefly, begomovirus and tomato plant.
Garcinol loaded vitamin E TPGS emulsified PLGA nanoparticles: preparation, physicochemical characterization, in vitro and in vivo studies
Authors: Gaonkar Raghuvir H. , Ganguly Soumya , Dewanjee Saikat , Sinha Samarendu , Gupta Amit , Ganguly Shantanu , Chattopadhyay Dipankar , Chatterjee Debnath Mita
Published: March 2017

Garcinol (GAR) is a naturally occurring polyisoprenylated phenolic compound. It has been recently investigated for its biological activities such as antioxidant, anti-inflammatory, anti ulcer, and antiproliferative effect on a wide range of human cancer cell lines. Though the outcomes are very promising, its extreme insolubility in water remains the main obstacle for its clinical application. Herein we report the formulation of GAR entrapped PLGA nanoparticles by nanoprecipitation method using vitamin E TPGS as an emulsifier. The nanoparticles were characterized for size, surface morphology, surface charge, encapsulation efficiency and in vitro drug release kinetics. The MTT assay depicted a high amount of cytotoxicity of GAR-NPs in B16F10, HepG2 and KB cells. A considerable amount of cell apoptosis was observed in B16f10 and KB cell lines. In vivo cellular uptake of fluorescent NPs on B16F10 cells was also investigated. Finally the GAR loaded NPs were radiolabeled with technetium-99m with >95% labeling efficiency and administered to B16F10 melanoma tumor bearing mice to investigate the in vivo deposition at the tumor site by biodistribution and scintigraphic imaging study. In vitro cellular uptake studies and biological evaluation confirm the efficacy of the formulation for cancer treatment.
Toroidal Dipolar Excitation in Metamaterials Consisting of Metal nanodisks and a Dielectrc Spacer on Metal Substrate
Authors: Tang Chaojun , Yan Bo , Wang Qiugu , Chen Jing , Yan Zhendong , Liu Fanxin , Chen Naibo , Sui Chenghua
Published: March 2017

We have investigated numerically toroidal dipolar excitation at optical frequency in metamaterials whose unit cell consists of three identical Ag nanodisks and a SiO2 spacer on Ag substrate. The near-field plasmon hybridization between individual Ag nanodisks and substrate forms three magnetic dipolar resonances, at normal incidence of plane electromagnetic waves. The strong coupling among three magnetic dipolar resonances leads to the toroidal dipolar excitation, when space-inversion symmetry is broke along the polarization direction of incident light. The influences of some geometrical parameters on the resonance frequency and the excitation strength of toroidal dipolar mode are studied in detail. The radiated power from toroidal dipole is also compared with that from conventional electric and magnetic multipoles.
Gene expression-based biomarkers for discriminating early and late stage of clear cell renal cancer
Authors: Bhalla Sherry , Chaudhary Kumardeep , Kumar Ritesh , Sehgal Manika , Kaur Harpreet , Sharma Suresh , Raghava Gajendra P. S.
Published: March 2017

In this study, an attempt has been made to identify expression-based gene biomarkers that can discriminate early and late stage of clear cell renal cell carcinoma (ccRCC) patients. We have analyzed the gene expression of 523 samples to identify genes that are differentially expressed in the early and late stage of ccRCC. First, a threshold-based method has been developed, which attained a maximum accuracy of 71.12% with ROC 0.67 using single gene NR3C2. To improve the performance of threshold-based method, we combined two or more genes and achieved maximum accuracy of 70.19% with ROC of 0.74 using eight genes on the validation dataset. These eight genes include four underexpressed (NR3C2, ENAM, DNASE1L3, FRMPD2) and four overexpressed (PLEKHA9, MAP6D1, SMPD4, C11orf73) genes in the late stage of ccRCC. Second, models were developed using state-of-art techniques and achieved maximum accuracy of 72.64% and 0.81 ROC using 64 genes on validation dataset. Similar accuracy was obtained on 38 genes selected from subset of genes, involved in cancer hallmark biological processes. Our analysis further implied a need to develop gender-specific models for stage classification. A web server, CancerCSP, has been developed to predict stage of ccRCC using gene expression data derived from RNAseq experiments.