bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic Profiling Exosomes from Vascular Smooth Muscle Cell
Authors: Qiu Hong , Shi Songshan , Wang Shunchun , Peng Hong , Ding Shi‐Jian , Wang Lianchun
Published: April 2018

Purpose

Vascular smooth muscle cells (VSMC) and endothelial cells (EC) communicate mutually to coordinate vascular development and homeostasis. Exosomes are emerging as one type of the mediators involved in this communication. Characterizing proteins in the exosomes is the critical first step in understanding how the VSMC‐EC crosstalk is mediated by exosomes.

Experimental design

The proteins in the human VSMC‐derived exosomes are profiled using nanoLC‐MS/MS based proteomics. The identified proteins are subjected to gene ontology analysis. The VSMC‐derived exosomes are also assessed for proangiogenic activity in vivo.

Results

Four hundred and fifty‐nine proteins are identified in the VSMC‐derived exosomes. Gene ontology analysis revealed that the exosome proteins are involved in 179 cellular components, 120 molecular functions, and 337 biological processes, with cell–cell adhesion and platelet activation/coagulation ranked at the top. VSMC‐derived exosomes do not display a proangiogenic activity in the in vivo angiogenesis assay, suggesting that the major function of VSMC‐derived exosomes is to maintain vessel homeostasis.

Conclusion and clinical relevance

The analyses obtained a systematic view of proteins in the VSMC‐derived exosomes, revealed the potential regulatory functions of the exosome in VSMC‐EC communication, and suggest that dysregulation of VSMC‐derived exosome‐mediated functions may disturb vessel homeostasis thereby contributing to vascular diseases.
Miscibility, Glass Transition Temperature and Mechanical Properties of NC/DBP Binary Systems by Molecular Dynamics
Authors: Lan Guanchao , Jin Shaohua , Li Jing , Wang Junying , Lu Zhiyan , Wu Nana , Li Lijie , Wang Dongxu
Published: April 2018

Molecular dynamics (MD) simulations were performed to research the miscibility, glass transition temperature (Tg) and mechanical properties of nitrocellulose/dibutyl phthalate (NC/DBP) binary systems. The solubility parameters (δ) of NC and DBP were calculated to predict the miscibility. NC and DBP are miscible as a result of a small Δδ(<2.0 MPa0.5) between the two components. The free volumes (VF) and density (ρ) of NC/DBP system were simulated to study theTg. It is found that theVFandρof NC/DBP changes regularly with the increase of DBP mass fraction and the transition occurs at the turning point. The simulation results demonstrate that DBP makes significant contribution to the reduction of theTgof NC. Additionally, the mechanical properties of NC/DBP systems including Young's moduli (E), Bulk moduli (K), Shear moduli (G) and Poisson's ratio (v) were calculated. The results reveal that with the increase of DBP mass fraction the ductility of NC/DBP improves while the brittleness decreases. Overall, a new and systematical method is proposed to study the miscibility,Tgand mechanical properties of polymers.
Spray particle drift mitigation using field corn (Zea mays L.) as a drift barrier
Authors: Vieira Bruno C , Butts Thomas R , Rodrigues Andre O , Golus Jeffrey A , Schroeder Kasey , Kruger Greg R
Published: April 2018

BACKGROUND

Herbicide particle drift reduces application efficacy and can cause severe impacts on nearby vegetation depending on the herbicide mode of action, exposure level, and tolerance to the herbicide. A particle drift mitigation effort placing windbreaks or barriers on the field boundaries to reduce off‐target movement of spray particles has been utilized in the past. The objective of this research was to evaluate the effectiveness of field corn (Zea mays L.) at different heights as a particle drift barrier.

RESULTS

Applications with a non‐air inclusion flat fan nozzle (ER11004) resulted in greater particle drift when compared with an air inclusion nozzle (TTI11004). Eight rows of corn were used as barriers (0.91, 1.22, and 1.98 m height) which reduced the particle drift for both nozzles, especially at shorter downwind distances. Applications with the ER11004 nozzle without corn barriers had 1% of the applied rate (D99) predicted to deposit at 14.8 m downwind, whereas this distance was reduced (up to 7‐fold) when applications were performed with corn barriers. The combination of corn drift barriers and nozzle selection (TTI11004) provided satisfactory particle drift reduction when the D99 estimates were compared with those for applications with the ER11004 nozzle without corn barriers (up to 10‐fold difference).

CONCLUSION

The corn drift barriers were effective in reducing particle drift from applications with the ER11004 and the TTI11004 nozzles (Fine and Ultra Coarse spray classifications, respectively). The corn drift barrier had appropriate porosity and width as the airborne spray was captured within its canopy instead of deflecting up and over it. © 2018 Society of Chemical Industry
UV‐C irradiation as a management tool for Tetranychus urticae on strawberries
Authors: Short Brent D , Janisiewicz Wojciech , Takeda Fumiomi , Leskey Tracy C
Published: April 2018

BACKGROUND

Tetranychus urticae Koch, the two‐spotted spider mite, is a highly polyphagous and worldwide pest of many agricultural crops, including fruit, vegetables, and ornamentals. Typical methods of control include applications of acaricides and biological control agents. Here, we present a non‐chemical technology for management of T. urticae on strawberry plants through the use of a nightly short‐duration ultraviolet‐C (UV‐C) irradiation treatment.

RESULTS

Potted strawberry plants infested with T. urticae that received a nightly 60‐s exposure of UV‐C irradiation had significantly fewer live mites per mid‐canopy leaflet (fewer than five) than untreated control plants (> 175). Furthermore, none of the UV‐C irradiated strawberry plants had any spider mite webbing; whereas, 65% of untreated plants were webbed. Tetranychus urticae feeding on untreated plants caused significant yellowing of the leaves compared with UV‐C‐treated plants.

CONCLUSION

The UV‐C irradiation treatment maintained mite populations below the accepted economic threshold of five mites per mid‐canopy leaflet. No phytotoxic effects were visible on plants exposed to the short‐duration nightly UV‐C irradiation treatments. Further discussion is provided on the potential benefits of UV‐C irradiation for mite management. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
Narrow windrow burning canola (Brassica napus L.) residue for Sclerotinia sclerotiorum (Lib.) de Bary sclerotia destruction
Authors: Brooks Kyran D , Bennett Sarita J , Hodgson Leon M , Ashworth Michael B
Published: April 2018

BACKGROUND

Since the introduction of herbicide‐tolerant varieties of canola (Brassica napus L.) in 1993, global plantings have increased resulting in an increased incidence of Sclerotinia sclerotiorum (Lib.) de Bary infections. Developments in narrow windrow burning techniques to destroy the seed of multiple herbicide‐resistant weeds provide an opportunity to also intercept and heat‐treat the S. sclerotiorum inoculum source, termed sclerotia, before it re‐enters the soil to infect susceptible crop species in successive years.

RESULTS

Preliminary kiln studies determined that a temperature of 264 °C for 10 s was needed to destroy S. sclerotiorum sclerotia viability (LT99) of sclerotia < 3 mm in diameter, whereas temperatures of 353 and 362 °C for the same duration were required to kill sclerotia (LT99) of 3–4 and > 4 mm in diameter respectively. In the field, temperatures > 500 °C were maintained in the centre of burning narrow windrows of canola residue for > 450 s and 300 °C was maintained consistently at either edge of the windrows for the same duration. The temperatures achieved when burning canola narrow windrows were sufficient to kill all sclerotia concentrated into the narrow windrow.

CONCLUSION

As a technique, narrow windrow burning of canola residue provides the temperature and temperature durations required to kill S. sclerotiorum sclerotia, thus providing a non‐fungicidal control option as part of a wider integrated disease management approach. © 2018 Society of Chemical Industry
Cardiac Progenitor Cells: The Matrix Has You
Authors: Castaldo Clotilde , Chimenti Isotta
Published: April 2018

Components of the cardiac extracellular matrix (ECM) are synthesized by residing cells and are continuously remodeled by them. Conversely, residing cells (including primitive cells) receive constant biochemical and mechanical signals from the ECM that modulate their biology. The pathological progression of heart failure affects all residing cells, inevitably causing profound changes in ECM composition and architecture that, in turn, impact on cell phenotypes. Any regenerative medicine approach must aim at sustaining microenvironment conditions that favor cardiogenic commitment of therapeutic cells and minimize pro-fibrotic signals, while conversely boosting the capacity of therapeutic cells to counteract adverse remodeling of the ECM. In this Perspective article, we discuss multiple issues about the features of an optimal scaffold for supporting cardiac tissue engineering strategies with cardiac progenitor cells, and, conversely, about the possible antifibrotic mechanisms induced by cell therapy.
Targeted maximum likelihood estimation for a binary treatment: A tutorial
Authors: Luque‐Fernandez Miguel Angel , Schomaker Michael , Rachet Bernard , Schnitzer Mireille E.
Published: April 2018

When estimating the average effect of a binary treatment (or exposure) on an outcome, methods that incorporate propensity scores, the G‐formula, or targeted maximum likelihood estimation (TMLE) are preferred over naïve regression approaches, which are biased under misspecification of a parametric outcome model. In contrast propensity score methods require the correct specification of an exposure model. Double‐robust methods only require correct specification of either the outcome or the exposure model. Targeted maximum likelihood estimation is a semiparametric double‐robust method that improves the chances of correct model specification by allowing for flexible estimation using (nonparametric) machine‐learning methods. It therefore requires weaker assumptions than its competitors. We provide a step‐by‐step guided implementation of TMLE and illustrate it in a realistic scenario based on cancer epidemiology where assumptions about correct model specification and positivity (ie, when a study participant had 0 probability of receiving the treatment) are nearly violated. This article provides a concise and reproducible educational introduction to TMLE for a binary outcome and exposure. The reader should gain sufficient understanding of TMLE from this introductory tutorial to be able to apply the method in practice. Extensive R‐code is provided in easy‐to‐read boxes throughout the article for replicability. Stata users will find a testing implementation of TMLE and additional material in the Appendix S1 and at the following GitHub repository: https://github.com/migariane/SIM‐TMLE‐tutorial
Sequential prevalence estimation with pooling and continuous test outcomes
Authors: Nguyen Ngoc T. , Bish Ebru K. , Aprahamian Hrayer
Published: April 2018

Prevalence estimation is crucial for controlling the spread of infections and diseases and for planning of health care services. Prevalence estimation is typically conducted via pooled, or group, testing due to limited testing budgets. We study a sequential estimation procedure that uses continuous pool readings and considers the dilution effect of pooling so as to efficiently estimate an unknown prevalence rate. Embedded into the sequential estimation procedure is an optimization model that determines the optimal pooling design (number of pools and pool sizes) under a limited testing budget, considering the trade‐off between testing cost and estimation accuracy. Our numerical study indicates that the proposed sequential estimation procedure outperforms single‐stage procedures, or procedures that use binary test outcomes. Further, the sequential procedure provides robust prevalence estimates in cases where the initial estimate of the unknown prevalence rate is poor, or the assumed distribution of the biomarker load in infected subjects is inaccurate. Thus, when limited and unreliable information is available about the current status of, or biomarker dynamics related to, an infection, the sequential procedure becomes an attractive estimation strategy, due to its ability to mitigate the initial bias.
Facile Preparation of High‐Performance Stretchable Fiber‐Like Electrodes and Supercapacitors
Authors: Ren Danyang , Dong Liubing , Wang Jinjie , Ma Xinpei , Xu Chengjun , Kang Feiyu
Published: April 2018

A facile preparation method was proposed to fabricate core‐sheath structured elastic cord/carbon nanotube (CNT)/polyaniline (PANI) composite fibers with excellent electrochemical performance and good mechanical stretchability. Specifically, we developed a “surface melting for stable attachment” strategy to combine CNT/PANI composite film tightly with elastic cord fiber. The fabricated fiber‐like elastic cord/CNT/PANI composite electrode displays a large gravimetric capacitance of 394 F g−1(corresponds to a linear specific capacitance of 15.4 mF cm−1) and superior rate capability. The electrode capacitance has no obvious decrease when the electrode was stretched from original state to a large stretch ratio of 100%, and the capacitance maintains 98% after 100 stretch‐release cycles; besides, the electrode at stretching state possesses almost same cycling stability and rate capability as it at original state. These results indicate robust micro‐structure and outstanding stretchability of our fiber‐like elastic cord/CNT/PANI composite electrode. Consequently, all‐solid‐state supercapacitors assembled based on the fiber‐like electrode also exhibit impressive stretchability. Overall, the proposed facile method for producing stretchable fiber‐like electrodes/supercapacitors is believed to further boost the practical application of stretchable and wearable energy storage devices.
Engage in yearlong planning for a smooth commencement
Authors: Hope Joan
Published: April 2018

“Commencement is really a yearlong endeavor,” said Alicia Engels, events manager at the University of Richmond. In fact, some arrangements are made years in advance, she said. For example, hotel blocks should be arranged once commencement dates are set, she said.
Customize the adult learner experience with responsive website design
Authors: Sutton Halley
Published: April 2018

SAN DIEGO — Adult learners come to your campus with a variety of life experiences, skills, and abilities. If you are part of a college system, how can you leverage the different areas of expertise at your system to best guide those adult learners to the program that is right for them, and eventually to completion? In a session at the annual conference of the Council for Adult and Experiential Learning, Veella Grooms, grant lead at Mountwest Community and Technical College; and Judith Whipkey, professor and department chair at BridgeValley Community and Technical College, shared how a Trade Adjustment Assistance Community College Career Training grant helped engage and make connections between adult learners at different campuses in the Community and Technical Colleges of West Virginia to guide them to completion.
Compare your career path with your peers'
Authors: Hope Joan
Published: April 2018

No one grows up planning to be a registrar. But what leads people into the registrar role? What is the typical career trajectory?
Winglet optimization for a model‐scale wind turbine
Authors: Hansen Thomas H. , Mühle Franz
Published: April 2018

A winglet optimization method is developed and tested for a model‐scale wind turbine. The best‐performing winglet shape is obtained by constructing a Kriging surrogate model, which is refined using an infill criterion based on expected improvement. The turbine performance is simulated by solving the incompressible Navier‐Stokes equations, and the turbulent flow is predicted using the Spalart‐Allmaras turbulence model. To validate the simulated performance, experiments are performed in the Norwegian University of Science and Technology wind tunnel. According to the simulations, the optimized winglet increases the turbine power and thrust by 7.8% and 6.3%, respectively. The wind tunnel experiments show that the turbine power increases by 8.9%, while the thrust increases by 7.4%. When introducing more turbulence in the wind tunnel to reduce laminar separation, the turbine power and thrust due to the winglet increases by 10.3% and 14.9%, respectively.
Russia: The Institutional Landscape of Russian Higher Education
Authors: Platonova Daria , Semyonov Dmitry
Published: April 2018

In this chapter we explore the higher education institutional landscape taking the case of the largest post-Soviet higher education system: Russia. In the Post-Soviet period, Russian higher education has tremendously expanded. The dramatic growth of the number of students and institutions has been facilitated by the introduction of tuition fees in public and a new private sector. The shifts in social and economic demand for professional fields affected the disciplinary and organisational structure of higher educational institutions.

The external forces (economic, political, social conditions) and higher education policy have been changing during the last decades. In the first part of the transitional period, the state provided limited regulation of the higher education system. In the 2000s, it has returned to its role of the main agent of change of the higher education system design. The diversity of institutional types that evolved in Russian higher education illustrate the consequences of massification and marketisation, such as new “broad access” segments and institutional programme drift. Also, the governmental role in shaping institutional diversity can be seen through attempts to increase vertical diversity (excellence initiatives), on the one hand, and to restrain it by closing down bottom-tier institutions, on the other.
Higher Education in Tajikistan: Institutional Landscape and Key Policy Developments
Authors: DeYoung Alan J. , Kataeva Zumrad , Jonbekova Dilrabo
Published: April 2018

Higher education in Tajikistan has undergone substantial changes over the past 25 years as a result of both its internal crises and those social and economic transition challenges seen throughout the Newly Independent States (NIS). HEIs in the country have also shown eagerness to change and grow as they move toward world education space. In this chapter, we examine the evolution of the Tajik system of higher education from the Soviet time through independence (1991–2015) in terms of growth, emerging landscape and diversification, and key policy developments and issues. We analyze these changes in the context of relevant economic, social and political factors, and rely on a comparative analysis in understanding the commonalities and differences in higher educational landscapes between Tajikistan and others in the NIS. Institutional diversity has occurred in the country along several dimensions. Among these is a geometric expansion of the number of HEIs: Those transformed from preexisting Soviet institutes as well as the establishment of many new ones. This has been fueled partly by the mass creation of new programs that reflect the needs of an emerging knowledge-based economy but also the result of parental craving for higher education for their children—regardless of market demands. Specific features of the massification of higher education in Tajikistan are further explained by internationalization according to the Bologna Process and other globalization agendas; the establishment of international HEIs under bilateral government agreements (with Russia), and significantly increasing HEI programs and enrolments in far-flung regions of the country—especially in programs related to industry and technology. Our analyses are based on a variety of official statistical sources; educational laws, institutional documents and reports published by international organizations; accounts from the English-language press; and open-ended interviews conducted by the authors in Tajikistan between 2011 and 2014.
Ukraine: Higher Education Reforms and Dynamics of the Institutional Landscape
Authors: Rumyantseva Nataliya L. , Logvynenko Olena I.
Published: April 2018

The chapter explores the developmental trajectory of Ukraine’s higher education system since the middle ages. Starting with just a few comprehensive universities in the western parts at first and later Eastern parts of the country, the system gradually evolved into a diverse and differentiated institutional landscape. The variety and scope of HEIs reflects the internal logic of the system’s own development as well as outside factors, including changes of the ruling governments, fluctuations in the demographic trends, shifts in political alliances and cultural and language oscillations, which have been characteristic of the Ukrainian history. The authors elaborate on several policy rationales that came to underpin some of the changes since the collapse of the Soviet Union as well as policy discussions and policy silences (lack of dialog amongst various stakeholders) that have taken a lot of energy and yet have not lead to any noticeable changes in the institutional scene. The chapter also discusses the most recent changes in the legislation and practical implementations leaving space for future research to draw conclusions as to their effectiveness.
Higher Education Transformation, Institutional Diversity and Typology of Higher Education Institutions in Azerbaijan
Authors: Isakhanli Hamlet , Pashayeva Aytaj
Published: April 2018

The development of higher education system of Azerbaijan reflects the country’s historical transformations. The system started developing with the foundation of the first higher education institution before the establishment of the Soviet Union, expanded during the Soviets and grew into current systems of 52 institutions since independence. Institutions changed in number and nature with the entrance of private universities into the higher education market and increase in number of state universities. Three-cycle higher education was introduced and institutions utilising Western university practices of management and teaching emerged. Despite the changes, the system still reflects much of the Soviet period. The typology of higher education institutions (HEIs) in Azerbaijan was built based on their educational, research, internationalisation activities and financial capacity. Institutions were classified as leading state and private higher education institutions, which excel in research and rank high in country ranking lists. The second group of institutions are known for good quality education but do not give a heavy weight on research. The last type of higher education institutions serve the purpose of preparing teachers and other public sector employees.
Metabolic syndrome and vaspin in patients with bipolar disorder
Authors: Ertekin Hulya , Sahin Basak , Caliskan Ali Metehan , Inanli Ikbal , Ertekin Yusuf Haydar
Published: April 2018

Metabolic disorders and abnormal levels of circulating adipokines have been reported in patients with bipolar disorder (BD). The aim of this study was to investigate the differences in the correlations of vaspin plasma levels and metabolic parameters between two groups: patients with BD and mentally healthy persons. We measured plasma levels of vaspin, metabolic parameters, and metabolic syndrome (MS) in 101 patients with BD and 90 healthy control (HC) subjects. Patients with BD were evaluated with the Young Mania Rating Scale (YMRS) to assess manic symptoms and the Hamilton Depression Scale (HDS) to assess depressive symptoms. The Global Assessment of Functioning (GAF) was used to evaluate the general functions of the patients. Body mass index (BMI), weight, waist circumference (WC), fasting glucose, and triglyceride levels of the study group were statistically higher than those of the healthy controls (p = 0.001, p < 0.001, p < 0.001, p = 0.027, and p = 0.001 respectively). Plasma levels of vaspin were 0.978 ng/ml in patients with BD and 0.292 in the HC group (p < 0.001). Our study revealed associations between metabolic parameters/metabolic syndrome and vaspin plasma concentrations in patients with BD. Vaspin can play a specific role in the pathogenesis of metabolic disorders in these subjects and can be a specific indicator substance in BD.
Theagnus dei, Catholic devotion, and confessional politics in early modern England
Authors: Muller Aislinn
Published: April 2018

After 1571 Catholic sacred objects were outlawed in England, and the possession of such objects could be prosecuted under the statute ofpraemunire. Despite this prohibition sacred objects including rosaries, blessed beads, and theagnus dei(wax pendants blessed by the pope) remained a critical part of Catholic devotion. This article examines the role of theagnus deiin English Catholic communities and the unique political connotations it acquired during the reign of Elizabeth I. It assesses the uses of these sacramentals in Catholic missions to England, their reception amongst Catholics, and the political significance of theagnus deiin light of the papal excommunication of Elizabeth I in 1570.
Relics, writing, and memory in the English Counter Reformation: Thomas Maxfield and his afterlives
Authors: Walsham Alexandra
Published: April 2018

This article explores the multiple and competing afterlives of the Jacobean martyr, Thomas Maxfield, who was executed at Tyburn in July 1616. It traces the evolution of his cult between the seventeenth and twenty-first centuries by exploring the migration of his relics alongside the movements of the written and printed texts recounting his life and death. It investigates the domestic and international politics in which these textual and material remains circulated and illuminates the making and metamorphosis of social memory in the English Counter Reformation. It sheds fresh light on how Maxfield’s relics served both to bind this imagined community together and to divide and fragment it. Highlighting the interweaving of devotion and scholarship, antiquarianism and piety, it also argues that relic collecting must be recognised as part of the wider contemporary enterprises of religious record-keeping and writing sacred history.
Interoception Enhanced via the Ears?
Authors: Hall J. K. , Lopes B. , Yu H.
Published: April 2018

Abstract. Heartbeat perception tasks are used to measure interoceptive accuracy. This paper explores the effect of reducing external auditory stimuli on heartbeat perception. Three samples (121 participants in total) performed a heartbeat perception task. Samples 1 and 2 wore ear-protectors and sample 3 did not. There were no differences in interoceptive accuracy between samples 1 and 2 but samples 1 and 2 showed significantly higher interoceptive accuracy than sample 3. These results suggest ear-protectors could be used to manipulate heartbeat perception and that the auditory component of heartbeat perception might be given greater consideration.
Multiple Imputation by Predictive Mean Matching When Sample Size Is Small
Authors: Kleinke Kristian
Published: April 2018

Abstract. Predictive mean matching (PMM) is a state-of-the-art hot deck multiple imputation (MI) procedure. The quality of its results depends, inter alia, on the availability of suitable donor cases. Applying PMM in small sample scenarios often found in psychological or medical research could be problematic, as there might not be many (or any) suitable donor cases in the data set. So far, there has not been any systematic research that examined the performance of PMM, when sample size is small. The present study evaluated PMM in various multiple regression scenarios, where sample size, missing data percentages, the size of the regression coefficients, and PMM’s donor selection strategy were systematically varied. Results show that PMM could be used in most scenarios, however results depended on the donor selection strategy: overall, PMM using either automatic distance-aided selection of donors ( Gaffert, Meinfelder, & Bosch, 2016 ) or using the nearest neighbor produced the best results.
Diagnosing the Warm Bias in the Central United States
Authors: Steiner Allison
Published: April 2018

A set of four papers published in JGR: Atmospheres present results from a project investigating why models predict warmer surface temperatures than are observed in the central United States.
Snowfall Rates from Satellite Data Help Weather Forecasters
Authors: Ferraro Ralph , Meng Huan , Zavodsky Brad , Kusselson Sheldon , Kann Deirdre , Guyer Brian , Jacobs Aaron , Perfater Sarah , Folmer Michael , Dong Jun , Kongoli Cezar , Yan Banghua , Wang Nai-Yu , Zhao Limin
Published: April 2018

A new data product calculates snowfall rates from weather data beamed directly from several satellites, helping meteorologists provide fast, accurate weather reports and forecasts.
Pancreatic β cells overexpressing hIAPP impaired mitophagy and unbalanced mitochondrial dynamics
Authors: Hernández Miriam García , Aguilar Ana García , Burillo Jesús , Oca Raquel Gómez , Manca Maria Antonietta , Novials Ana , Alcarraz-Vizan Gema , Guillén Carlos , Benito Manuel
Published: April 2018

Human islet amyloid polypeptide (hIAPP), or amylin, has the tendency to aggregate into insoluble amyloid fibrils, a typical feature of islets from type 2 diabetes individuals. Thus, we investigated comparatively the impact of hIAPP on key pathways involved in pancreatic beta survival. INS1E-hIAPP cells present a hyperactivation of MTORC1 and an inhibition of autophagy signaling, those cells showing an increase in cell size. Resveratrol, a MTORC1 inhibitor, can reverse TSC2 degradation that occurs in INS1E-hIAPP cells and diminished MTORC1 hyperactivation with concomitant autophagy stimulation. At the same time, a blockade in mitophagy was found in INS1E-hIAPP cells, as compared with control or INS1E-rIAPP cells. Consistently, human amylin overexpression generates a basal induction of nitrotyrosine levels and polyubiquitinated aggregates. Failure of the protein degradation machinery finally results in an accumulation of damaged and fissioned mitochondria, ROS production, and increased susceptibility to endoplasmic reticulum (ER)-stress-induced apoptosis. Overall, hIAPP overexpression in INS1E cells induced MTORC1 activation and mitophagy inhibition, favoring a pro-fission scenario of damaged mitochondria, these cells turn out to be more susceptible to the ER-stress-induced apoptosis and malfunction.
Oxygen minimum zone cryptic sulfur cycling sustained by offshore transport of key sulfur oxidizing bacteria
Authors: Callbeck Cameron M. , Lavik Gaute , Ferdelman Timothy G. , Fuchs Bernhard , Gruber-Vodicka Harald R. , Hach Philipp F. , Littmann Sten , Schoffelen Niels J. , Kalvelage Tim , Thomsen Sören , Schunck Harald , Löscher Carolin R. , Schmitz Ruth A. , Kuypers Marcel M. M.
Published: April 2018

Members of the gammaproteobacterial clade SUP05 couple water column sulfide oxidation to nitrate reduction in sulfidic oxygen minimum zones (OMZs). Their abundance in offshore OMZ waters devoid of detectable sulfide has led to the suggestion that local sulfate reduction fuels SUP05-mediated sulfide oxidation in a so-called “cryptic sulfur cycle”. We examined the distribution and metabolic capacity of SUP05 in Peru Upwelling waters, using a combination of oceanographic, molecular, biogeochemical and single-cell techniques. A single SUP05 species,
U
Thioglobus perditus, was found to be abundant and active in both sulfidic shelf and sulfide-free offshore OMZ waters. Our combined data indicated that mesoscale eddy-driven transport led to the dispersal of
U
T. perditus and elemental sulfur from the sulfidic shelf waters into the offshore OMZ region. This offshore transport of shelf waters provides an alternative explanation for the abundance and activity of sulfide-oxidizing denitrifying bacteria in sulfide-poor offshore OMZ waters.
Native mass spectrometry combined with enzymatic dissection unravels glycoform heterogeneity of biopharmaceuticals
Authors: Wohlschlager Therese , Scheffler Kai , Forstenlehner Ines C. , Skala Wolfgang , Senn Stefan , Damoc Eugen , Holzmann Johann , Huber Christian G.
Published: April 2018

Robust manufacturing processes resulting in consistent glycosylation are critical for the efficacy and safety of biopharmaceuticals. Information on glycosylation can be obtained by conventional bottom–up methods but is often limited to the glycan or glycopeptide level. Here, we apply high-resolution native mass spectrometry (MS) for the characterization of the therapeutic fusion protein Etanercept to unravel glycoform heterogeneity in conditions of hitherto unmatched mass spectral complexity. Higher spatial resolution at lower charge states, an inherent characteristic of native MS, represents a key component for the successful revelation of glycan heterogeneity. Combined with enzymatic dissection using a set of proteases and glycosidases, assignment of specific glycoforms is achieved by transferring information from subunit to whole protein level. The application of native mass spectrometric analysis of intact Etanercept as a fingerprinting tool for the assessment of batch-to-batch variability is exemplified and may be extended to demonstrate comparability after changes in the biologic manufacturing process.
Theoretical principles of transcription factor traffic on folded chromatin
Authors: Cortini Ruggero , Filion Guillaume J.
Published: April 2018

All organisms regulate transcription of their genes. To understand this process, a complete understanding of how transcription factors find their targets in cellular nuclei is essential. The DNA sequence and other variables are known to influence this binding, but the distribution of transcription factor binding patterns remains mostly unexplained in metazoan genomes. Here, we investigate the role of chromosome conformation in the trajectories of transcription factors. Using molecular dynamics simulations, we uncover the principles of their diffusion on chromatin. Chromosome contacts play a conflicting role: at low density they enhance transcription factor traffic, but at high density they lower it by volume exclusion. Consistently, we observe that in human cells, highly occupied targets, where protein binding is promiscuous, are found at sites engaged in chromosome loops within uncompacted chromatin. In summary, we provide a framework for understanding the search trajectories of transcription factors, highlighting the key contribution of genome conformation.
Linear mitochondrial DNA is rapidly degraded by components of the replication machinery
Authors: Peeva Viktoriya , Blei Daniel , Trombly Genevieve , Corsi Sarah , Szukszto Maciej J. , Rebelo-Guiomar Pedro , Gammage Payam A. , Kudin Alexei P. , Becker Christian , Altmüller Janine , Minczuk Michal , Zsurka Gábor , Kunz Wolfram S.
Published: April 2018

Emerging gene therapy approaches that aim to eliminate pathogenic mutations of mitochondrial DNA (mtDNA) rely on efficient degradation of linearized mtDNA, but the enzymatic machinery performing this task is presently unknown. Here, we show that, in cellular models of restriction endonuclease-induced mtDNA double-strand breaks, linear mtDNA is eliminated within hours by exonucleolytic activities. Inactivation of the mitochondrial 5′-3′exonuclease MGME1, elimination of the 3′-5′exonuclease activity of the mitochondrial DNA polymerase POLG by introducing the p.D274A mutation, or knockdown of the mitochondrial DNA helicase TWNK leads to severe impediment of mtDNA degradation. We do not observe similar effects when inactivating other known mitochondrial nucleases (EXOG, APEX2, ENDOG, FEN1, DNA2, MRE11, or RBBP8). Our data suggest that rapid degradation of linearized mtDNA is performed by the same machinery that is responsible for mtDNA replication, thus proposing novel roles for the participating enzymes POLG, TWNK, and MGME1.
An effector from the Huanglongbing-associated pathogen targets citrus proteases
Authors: Clark Kelley , Franco Jessica Yvette , Schwizer Simon , Pang Zhiqian , Hawara Eva , Liebrand Thomas W. H. , Pagliaccia Deborah , Zeng Liping , Gurung Fatta B. , Wang Pengcheng , Shi Jinxia , Wang Yinsheng , Ancona Veronica , van der Hoorn Renier A. L. , Wang Nian , Coaker Gitta , Ma Wenbo
Published: April 2018

The citrus industry is facing an unprecedented challenge from Huanglongbing (HLB). All cultivars can be affected by the HLB-associated bacterium ‘Candidatus Liberibacter asiaticus’ (CLas) and there is no known resistance. Insight into HLB pathogenesis is urgently needed in order to develop effective management strategies. Here, we use Sec-delivered effector 1 (SDE1), which is conserved in all CLas isolates, as a molecular probe to understand CLas virulence. We show that SDE1 directly interacts with citrus papain-like cysteine proteases (PLCPs) and inhibits protease activity. PLCPs are defense-inducible and exhibit increased protein accumulation in CLas-infected trees, suggesting a role in citrus defense responses. We analyzed PLCP activity in field samples, revealing specific members that increase in abundance but remain unchanged in activity during infection. SDE1-expressing transgenic citrus also exhibit reduced PLCP activity. These data demonstrate that SDE1 inhibits citrus PLCPs, which are immune-related proteases that enhance defense responses in plants.
Highly nitrogen doped carbon nanofibers with superior rate capability and cyclability for potassium ion batteries
Authors: Xu Yang , Zhang Chenglin , Zhou Min , Fu Qun , Zhao Chengxi , Wu Minghong , Lei Yong
Published: April 2018

Potassium-ion batteries are a promising alternative to lithium-ion batteries. However, it is challenging to achieve fast charging/discharging and long cycle life with the current electrode materials because of the sluggish potassiation kinetics. Here we report a soft carbon anode, namely highly nitrogen-doped carbon nanofibers, with superior rate capability and cyclability. The anode delivers reversible capacities of 248 mAh g–1 at 25 mA g–1 and 101 mAh g–1 at 20 A g–1, and retains 146 mAh g–1 at 2 A g–1 after 4000 cycles. Surface-dominated K-storage is verified by quantitative kinetics analysis and theoretical investigation. A full cell coupling the anode and Prussian blue cathode delivers a reversible capacity of 195 mAh g–1 at 0.2 A g–1. Considering the cost-effectiveness and material sustainability, our work may shed some light on searching for K-storage materials with high performance.
The LetA/S two-component system regulates transcriptomic changes that are essential for the culturability of Legionella pneumophila in water
Authors: Mendis Nilmini , McBride Peter , Saoud Joseph , Mani Thangadurai , Faucher Sebastien P.
Published: April 2018

Surviving the nutrient-poor aquatic environment for extended periods of time is important for the transmission of various water-borne pathogens, including Legionella pneumophila (Lp). Previous work concluded that the stringent response and the sigma factor RpoS are essential for the survival of Lp in water. In the present study, we investigated the role of the LetA/S two-component signal transduction system in the successful survival of Lp in water. In addition to cell size reduction in the post-exponential phase, LetS also contributes to cell size reduction when Lp is exposed to water. Importantly, absence of the sensor kinase results in a significantly lower survival as measured by CFUs in water at various temperatures and an increased sensitivity to heat shock. According to the transcriptomic analysis, LetA/S orchestrates a general transcriptomic downshift of major metabolic pathways upon exposure to water leading to better culturability, and likely survival, suggesting a potential link with the stringent response. However, the expression of the LetA/S regulated small regulatory RNAs, RsmY and RsmZ, is not changed in a relAspoT mutant, which indicates that the stringent response and the LetA/S response are two distinct regulatory systems contributing to the survival of Lp in water.
Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages
Authors: Roy Sugata , Schmeier Sebastian , Kaczkowski Bogumil , Arner Erik , Alam Tanvir , Ozturk Mumin , Tamgue Ousman , Parihar Suraj P. , Kawaji Hideya , Itoh Masayoshi , Lassmann Timo , Carninci Piero , Hayashizaki Yoshihide , Forrest Alistair R. R. , Guler Reto , Bajic Vladimir B. , Brombacher Frank , Suzuki Harukazu
Published: April 2018

Mycobacterium tuberculosis (Mtb) infection reveals complex and dynamic host-pathogen interactions, leading to host protection or pathogenesis. Using a unique transcriptome technology (CAGE), we investigated the promoter-based transcriptional landscape of IFNγ (M1) or IL-4/IL-13 (M2) stimulated macrophages during Mtb infection in a time-kinetic manner. Mtb infection widely and drastically altered macrophage-specific gene expression, which is far larger than that of M1 or M2 activations. Gene Ontology enrichment analysis for Mtb-induced differentially expressed genes revealed various terms, related to host-protection and inflammation, enriched in up-regulated genes. On the other hand, terms related to dis-regulation of cellular functions were enriched in down-regulated genes. Differential expression analysis revealed known as well as novel transcription factor genes in Mtb infection, many of them significantly down-regulated. IFNγ or IL-4/IL-13 pre-stimulation induce additional differentially expressed genes in Mtb-infected macrophages. Cluster analysis uncovered significant numbers, prolonging their expressional changes. Furthermore, Mtb infection augmented cytokine-mediated M1 and M2 pre-activations. In addition, we identified unique transcriptional features of Mtb-mediated differentially expressed lncRNAs. In summary we provide a comprehensive in depth gene expression/regulation profile in Mtb-infected macrophages, an important step forward for a better understanding of host-pathogen interaction dynamics in Mtb infection.
Author Correction: Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model
Authors: Satou Yorifumi , Katsuya Hiroo , Fukuda Asami , Misawa Naoko , Ito Jumpei , Uchiyama Yoshikazu , Miyazato Paola , Islam Saiful , Fassati Ariberto , Melamed Anat , Bangham Charles R. M. , Koyanagi Yoshio , Sato Kei
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Mycobacterium marinum infections in Denmark from 2004 to 2017: A retrospective study of incidence, patient characteristics, treatment regimens and outcome
Authors: Holden Inge K. , Kehrer Michala , Andersen Aase B. , Wejse Christian , Svensson Erik , Johansen Isik Somuncu
Published: April 2018

Mycobacterium marinum (M. marinum) is a slowly growing nontuberculous mycobacterium. The incidence of M. marinum infections in Denmark is unknown. We conducted a retrospective nationwide study including all culture confirmed cases of M. marinum from 2004 to 2017 in Denmark. All available medical records were reviewed. Demographics, clinical characteristics, and treatment regiments were analyzed. Fifty-five patients were identified, 40 (72.7%) were men with a median age of 50 years. Aquatic exposure was reported by 48 (90.6%) of the patients. Site of infection was upper extremities in 49 (92.5%) patients and 49 (92.5%) had superficial infection. The median time from symptom presentation to diagnosis was 194 days. All patients received antibiotics. Median time of treatment duration among all patients was 112 days. Treatment outcome was classified as improved in 40 (75%), improved with sequela in 4 (7.6%) patients and only 3 patients (3.8%) were classified as failed. Infection with M. marinum is rare and there is a long delay from symptom manifestation to diagnosis. The infection is predominantly related to aquatic exposure. M. marinum should be a differential diagnose in patients with slow-developing cutaneous elements and relevant exposure. Treatment outcomes are overall good and severe sequela are rare.
Author Correction: Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells
Authors: Ito Naoki , Kii Isao , Shimizu Noriaki , Tanaka Hirotoshi , Takeda Shin’ichi
Published: April 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Publisher Correction: Normal-to-mildly increased albuminuria predicts the risk for diabetic retinopathy in patients with type 2 diabetes
Authors: Lee Min-Kyung , Han Kyung-Do , Lee Jae-Hyuk , Sohn Seo-Young , Hong Oak-Kee , Jeong Jee-Sun , Kim Mee-Kyoung , Baek Ki-Hyun , Song Ki-Ho , Kwon Hyuk-Sang
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Association between maternal exposure to phthalates and lower language ability in offspring derived from hair metabolome analysis
Authors: Jones Beatrix , Han Ting-Li , Delplancke Thibaut , McKenzie Elizabeth J. , de Seymour Jamie V. , Chua Mei Chien , Tan Kok Hian , Baker Philip N.
Published: April 2018

The fetus undergoes a crucial period of neurodevelopment in utero. The maternal hair metabolome provides an integrated record of the metabolic state of the mother prior to, and during pregnancy. We investigated whether variation in the maternal hair metabolome was associated with neurodevelopmental differences across infants. Maternal hair samples and infant neurocognitive assessments (using the Bayley III Scales of Infant Development at 24 months) were obtained for 373 infant-mother dyads between 26–28 weeks’ gestation from the Growing Up in Singapore Towards Healthy Outcomes cohort. The hair metabolome was analysed using gas chromatography-mass spectrometry. Intensity measurements were obtained for 276 compounds. After controlling for maternal education, ethnicity, and infant sex, associations between metabolites and expressive language skills were detected, but not for receptive language, cognitive or motor skills. The results confirm previous research associating higher levels of phthalates with lower language ability. In addition, scores were positively associated with a cluster of compounds, including adipic acid and medium-chain fatty acids. The data support associations between the maternal hair metabolome and neurodevelopmental processes of the fetus. The association between phthalates and lower language ability highlights a modifiable risk factor that warrants further investigation.
Preliminary evidence of altered neural response during intertemporal choice of losses in adult attention-deficit hyperactivity disorder
Authors: Tanaka Saori C. , Yahata Noriaki , Todokoro Ayako , Kawakubo Yuki , Kano Yukiko , Nishimura Yukika , Ishii-Takahashi Ayaka , Ohtake Fumio , Kasai Kiyoto
Published: April 2018

Impulsive behaviours are common symptoms of attention-deficit hyperactivity disorder (ADHD). Although previous studies have suggested functional models of impulsive behaviour, a full explanation of impulsivity in ADHD remains elusive. To investigate the detailed mechanisms behind impulsive behaviour in ADHD, we applied an economic intertemporal choice task involving gains and losses to adults with ADHD and healthy controls and measured brain activity by functional magnetic resonance imaging. In the intertemporal choice of future gains, we observed no behavioural or neural difference between the two groups. In the intertemporal choice of future losses, adults with ADHD exhibited higher discount rates than the control participants. Furthermore, a comparison of brain activity representing the sensitivity of future loss in the two groups revealed significantly lower activity in the striatum and higher activity in the amygdala in adults with ADHD than in controls. Our preliminary findings suggest that an altered size sensitivity to future loss is involved in apparent impulsive choice behaviour in adults with ADHD and shed light on the multifaceted impulsivity underlying ADHD.