bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of (methacryloxymethyl)methyldimethoxysilane on DCP cured EPDM/PP thermoplastic vulcanizates
Authors: Mali Manoj , Marathe Aditi , Mhaske Shashank
Published: September 2017

In this study, the effect of (methacryloxymethyl)methyldimethoxysilane (MM‐MDMS) concentration on the mechanical, thermal, thermomechanical, rheological, morphological, gel content, cross‐linking density, and compression set properties of dynamically vulcanized ethylene propylene diene monomer (EPDM)/polypropylene (PP) (60/40, w/w) based thermoplastic vulcanizates (TPVs) was carried out. MM‐MDMS induces the physical cross‐linking and grafting as well as enhances chemical cross‐linking between PP and EPDM. This results increment in the values of cross‐linking density, gel content, tensile strength, Young's modulus, elongation at break, and viscosity. In contrast, the values of compression set, melting temperature, enthalpy of melting, crystallinity, and damping factor were observed to decrease with increased addition of MM‐MDMS in the EPDM/PP based TPV. This has been supported by Fourier transform infrared spectroscopy spectra and thermomechanical analysis. Scanning electron microscopy analysis confirmed the increase in compatibility between EPDM and PP on addition of MM‐MDMS. J. VINYL ADDIT. TECHNOL., 24:304–313, 2018. © 2017 Society of Plastics Engineers
Imagining the Chorus in Augustan Poetry
Authors: Curtis Lauren
Published: September 2017

From archaic Sparta to classical Athens the chorus was a pervasive feature of Greek social and cultural life. Until now, however, its reception in Roman literature and culture has been little appreciated. This book examines how the chorus is reimagined in a brief but crucial period in the history of Latin literature, the early Augustan period from 30 to 10 BCE. It argues that in the work of Horace, Virgil, and Propertius, the language and imagery of the chorus articulate some of their most pressing concerns surrounding social and literary belonging in a rapidly changing Roman world. By re-examining seminal Roman texts such as Horace's Odes and Virgil's Aeneid from this fresh perspective, the book connects the history of musical culture with Augustan poetry's interrogation of fundamental questions surrounding the relationship between individual and community, poet and audience, performance and writing, Greek and Roman, and tradition and innovation.
Meltwater runoff in a changing climate (1951–2099) at Chhota Shigri Glacier, Western Himalaya, Northern India
Authors: Engelhardt Markus , Leclercq Paul , Eidhammer Trude , Kumar Pankaj , Landgren Oskar , Rasmussen Roy
Published: September 2017

Meltwater runoff in the catchment area containing Chhota Shigri glacier (Western Himalaya) is simulated for the period 1951–2099. The applied mass-balance model is forced by downscaled products from four regional climate models with different horizontal resolution. For the future climate scenarios we use high resolution time series of 5 km grid spacing, generated using the newly developed Intermediate Complexity Atmospheric Research Model. The meteorological input is downscaled to 300 m horizontal resolution. The use of an ice flow model provides annually updated glacier area for the mass-balance calculations. The mass-balance model calculates daily snow accumulation, melt, runoff, as well as the individual runoff components (glacial melt, snowmelt and rain). The resulting glacier area decreases by 35% (representative concentration pathway (RCP) 4.5 scenario) to 70% (RCP 8.5 scenario) by 2099 relative to 2000. The average annual mass balance over the whole model period (1951–2099) was –0.4 (±0.3) m w.e. a–1. Average annual runoff does not differ substantially between the two climate scenarios. However, for the years after 2040 our results show a shift towards earlier snowmelt onset that increases runoff in May and June, and reduced glacier melt that decreases runoff in August and September. This shift is much stronger pronounced in the RCP 8.5 scenario.
The emperor, the sultan and the scholar: the portrayal of the Ottomans in theDialogue with a Persianof Manuel II Palaiologos
Authors: Çelik Siren
Published: September 2017

This article will attempt to offer the first literary analysis of theDialogue with a Persianof Manuel II Palaiologos. Despite its rich theological and literary material, this work has largely been neglected by scholars. However, theDialoguedeserves to be studied for its literary merit and not merely as a historical source. After a brief overview of the contents and background of theDialogue, this study will focus on its literary features, especially on the vivid character portrayal of the Ottomans and the emperor himself.
Climate Dynamics, Invader Fitness, and Ecosystem Resistance in an Invasion-Factor Framework
Authors: Young Stephen L. , Clements David R. , DiTommaso Antonio
Published: September 2017

As researchers and land managers increasingly seek to understand plant invasions and the external (climate) and internal (plant genetics) conditions that govern the process, new insight is helping to answer the elusive question of what makes some invasions successful and others not. Plant invasion success or failure is based on a combination of evolutionary and ecological processes. Abiotic (e.g., climate) and biotic (e.g., plant competition) conditions in the environment and plant genetics (e.g., fitness) combine in either decreasing or increasing invasion, yet it has proven challenging to know exactly which of these conditions leads to success for a given species, even when a wealth of empirical data is available. Further, current regional distribution models for invasive plant species rarely consider biotic and fitness interactions, instead focusing primarily on abiotic conditions. The crucial role of all three factors (climate dynamics, invader fitness, and ecosystem resistance) must not be ignored. Here we construct a three-factor invasion framework from which we develop conceptual models using empirical studies for yellow starthistle, nonnative common reed, and musk thistle, three dissimilar but commonly occurring invasive plant species in North America. We identify how components of the invasion process—rapid population increase, established local dominance, and rapid range expansion—are influenced by ecosystem resistance, invader fitness, and/or climate dynamics, a set of broadly defined factors for each of the three invasive plant species. Our framework can be used to (1) establish research priorities, (2) address gaps in theoretical understanding, and (3) identify invasion process components that can be targeted to improve management. Building on previous models, our unifying framework, which can be used for assessing any invasive plant species having sufficient empirical data, simultaneously shows the influence of ecosystem resistance, invader fitness, and climate dynamics factors on the invasion process.
The impact of gender diversity on performance: The moderating role of industry, alliance network, and family-friendly policies – Evidence from Korea
Authors: Bae Kwang Bin , Skaggs Sheryl
Published: September 2017

This study analyzes the effects of gender diversity in management on organizational performance using Korea Workplace Panel Survey data for 2005, 2007, and 2009. Few studies have examined this relationship for firms outside the United States, particularly in Asian countries. Similar to previous research, our findings show that gender diversity in management has a U-shaped relationship with firm productivity. Second, the curvilinear relationship between gender diversity in management and firm productivity is stronger in service-oriented industries relative to manufacturing industries, with the highest level of employee productivity within homogeneous management groups. Third, we include a measure of workplace family-friendly policies to moderate the relationship between gender diversity in management and organizational performance. We find that the U-shaped pattern also holds in firms with a large number of family-friendly policies. This suggests that gender diversity in management has considerable influence on the productivity of Korean firms through interactions with family-friendly policies.
The spatial context of organizations: A critique of ‘creative workspaces’
Authors: De Paoli Donatella , Sauer Erika , Ropo Arja
Published: September 2017

This paper examines office design as a spatial context of organizations. Organizations increasingly invest in designing workspaces to support employee creativity, foster company innovation and communicate a positive company image. This paper takes a critical view of this ‘hype’ by describing and analysing images of the headquarters of allegedly ‘creative workspaces’ published on the internet across a broad range of industries and corporations. Our analysis shows how their design follows standardized or stereotypical approaches to nurturing creativity: playfully or artistically designed open spaces, environments reminiscent of home, sports and play, nature, past/future technologies, or culturally aligned symbols. We discern underlying connections between office spaces and creativity, suggesting that creativity flourishes in happy, relaxed and playful communities within close-knit teams. We then identify three contradictions in relation to the existing literature on creativity and workspaces: individually versus collectively produced creativity; professionally designed workspaces versus workspaces created through participation; and planned versus emerging creativity.
Ultrasonic bone aspirator use in endoscopic ear surgery: feasibility and safety assessed using cadaveric temporal bones
Authors: Gardner E G , Sappington J , Arriaga M A , Kanotra S P
Published: September 2017

Objectives:

To describe the feasibility and assess the safety of using an ultrasonic bone aspirator in endoscopic ear surgery.

Methods:

Five temporal bones were dissected via endoscopic ear surgery using a Sonopet ultrasonic bone aspirator. Atticoantrostomy was undertaken. Another four bones were dissected using routine endoscopic equipment and standard bone curettes in a similar manner. Feasibility and safety were assessed in terms of: dissection time, atticoantrostomy adequacy, tympanomeatal flap damage, chorda tympani nerve injury, ossicular injury, ossicular chain disruption, facial nerve exposure and dural injury.

Results:

The time taken to perform atticoantrostomy was significantly less with the use of the ultrasonic bone aspirator as compared to conventional bone curettes.

Conclusion:

The ultrasonic bone aspirator is a feasible option in endoscopic ear surgery. It enables easy bone removal, with no additional complications and greater efficacy than traditional bone curettes. It should be a part of the armamentarium for transcanal endoscopic ear surgery.
From Language to Script: Graphic practice and the politics of authority in Santali-language print media, eastern India
Authors: CHOKSI NISHAANT
Published: September 2017

This article discusses the way in which assemblages of technologies, political institutions, and practices of exchange have rendered both language and script a site for an ongoing politics of authority among Santals, an Austro-Asiatic speaking Adivasi (Scheduled Tribe) community spread throughout eastern India. It focuses particularly on the production of Santali-language print artefacts, which, like its dominant language counterparts, such as Bengali, has its roots in colonial-era Christian missions. However, unlike dominant languages, Santali-language media has been characterized by the use of multiple graphic registers, including a missionary-derived Roman script, Indic scripts such as Devanagari and Eastern Brahmi, and an independently derived script, Ol-Chiki. The article links the history of Santali print and graphic practice with assertions of autonomy in colonial and early post-colonial India. It then ethnographically documents how graphic practices, in particular the use of multiple scripts, and print technologies mediate a contemporary politics of authority along vectors such as class and generation within communities that speak and read Santali in the eastern state of West Bengal, India.
OPTIMAL POLICY IN COLLATERAL CONSTRAINED ECONOMIES
Authors: Biljanovska Nina
Published: September 2017

This paper examines optimal policy in a macroeconomic model with collateral constraints. Binding collateral constraints yield inefficient competitive equilibrium allocations because they distort the optimal utilization of real resources. I identify the set of policy instruments that can be used by a Ramsey planner to achieve the first-best and the second-best (i.e., constrained planner's) allocations. A system of distortionary taxes on capital and labor income, along with direct lump-sum transfers among borrowers and lenders replicates the first-best outcome. The tax rates correct for the marginal distortions, whereas the direct lump-sum transfers perform income redistributions among the agents. In absence of direct lump-sum transfers, the distortionary taxes have an additional role, i.e., to perform implicit income transfers, and only second-best outcomes are attainable. I also derive the optimal policy in response to real and financial shocks, and show how the policy recommendations differ depending on the set of policy instruments available.
Postnatal Developmental Changes in Fractal Complexity of Giemsa-Stained Chromatin in Mice Spleen Follicular Cells
Authors: Pantic Igor , Paunovic Jovana , Vucevic Danijela , Radosavljevic Tatjana , Dugalic Stefan , Petkovic Anita , Radojevic-Skodric Sanja , Pantic Senka
Published: September 2017

Although there are numerous recent works focusing on fractal properties of DNA and chromatin, many issues regarding changes in chromatin fractality during physiological aging remain unclear. In this study, we present results indicating that in mice, there is an age-related reduction of chromatin fractal complexity in a population of spleen follicular cells (SFCs). Spleen tissue was obtained from 16 mice and fixated in Carnoy solution. The youngest animal was newborn, and each animal was exactly 1 month older than the previous. We performed fractal analysis of SFC chromatin structure, stained using Giemsa technique. Fractal analysis was done in a plugin algorithm of ImageJ software. We also performed gray-level co-occurrence matrix (GLCM) analysis of all chromatin structures with the calculation of parameters such as angular second moment and inverse difference moment. Giemsa-stained SFC chromatin exhibited an age-dependent reduction of fractal dimension with statistically significant (p<0.01) linear trend. Moreover, there was a statistically significant increase of SFC chromatin lacunarity. The chromatin GLCM parameters did not significantly change. To our knowledge, this is the first study to perform fractal and GLCM analyses of SFC chromatin and to investigate potential changes of fractal parameters during postnatal development.
Judicial Supremacy, Judicial Power, and the Finality of Constitutional Rulings
Authors: Lemieux Scott E.
Published: September 2017

It is widely assumed that the Supreme Court of the United States has established supremacy over contested constitutional questions, with the power to make final determinations of constitutional meaning. Since the 1960s, most scholars have assumed that legislatures and courts are engaged in a power struggle in which countermajoritarian courts can assert their will over majoritarian legislatures. More recently, a new generation of scholarship has demonstrated that judicial power often expands as a result of the willful empowerment of the judiciary by actors in other branches. Most scholars working with the latter framework, however, do not dispute that the United States has a regime of judicial supremacy—they simply see the political empowerment of courts as an explanation for why judicial supremacy has emerged despite the initially weak position of the judiciary. I argue that the insights of the political empowerment literature should be pressed further. It makes little sense to use the general label “judicial supremacy” for a system in which judicial power remains dependent on choices made by other political actors. Examining several cases that are generally seen as canonical examples of assertions of judicial supremacy, I find that courts were unable to settle constitutional debates, and in addition often either were unable to achieve their policy aims or did not actually require other political actors to do anything. The logic of new empirical findings about the sources of judicial power should compel scholars to question whether aggressive assertions of supremacy in judicial opinions are in fact accurate descriptions of how judicial power functions in the United States.
Local sourcing and the military: Lessons learned through a university-based initiative to increase local procurement at a US military base
Authors: Dunning Rebecca , Day John , Creamer Nancy
Published: September 2017

The volume of food purchased by the American military makes it perhaps the single largest intermediated market for food in the USA. Consequently, it is not surprising that those seeking to enhance the economic viability of small and mid-scale farms may view military bases as a promising market for locally produced foods. This is a challenging prospect, however, due to the centralized structure of military command, the nature of the military procurement system and federal mandates to obtain products that maximize value at the lowest available cost. This paper describes the US military food procurement system and the work of a 3-yr initiative to increase the amount of locally produced, source-identified products used at a North Carolina military installation. Our experiences serve as a cautionary tale, with this paper designed as both a primer on ‘how it works’ for food procurement at the federal and base level, and a description of our largely unsuccessful attempts to increase the volume of local food products from small-/mid-scale producers moving through the supply chain into base dining halls and restaurants. Based on our experiences, we also make recommendations on possible entry points for local food and farm advocates to work within the existing system to localize food procurement.
Standard comparison of local mental health care systems in eight European countries
Authors: Gutiérrez-Colosía M. R. , Salvador-Carulla L. , Salinas-Pérez J. A. , García-Alonso C. R. , Cid J. , Salazzari D. , Montagni I. , Tedeschi F. , Cetrano G. , Chevreul K. , Kalseth J. , Hagmair G. , Straßmayr C. , Park A. L. , Sfectu R. , Ala-Nikkola T. , González-Caballero J. L. , Rabbi L. , Kalseth B. , Amaddeo F. ,   For the REFINEMENT Group
Published: September 2017

Aims.

There is a need of more quantitative standardised data to compare local Mental Health Systems (MHSs) across international jurisdictions. Problems related to terminological variability and commensurability in the evaluation of services hamper like-with-like comparisons and hinder the development of work in this area. This study was aimed to provide standard assessment and comparison of MHS in selected local areas in Europe, contributing to a better understanding of MHS and related allocation of resources at local level and to lessen the scarcity in standard service comparison in Europe. This study is part of the Seventh Framework programme REFINEMENT (Research on Financing Systems’ Effect on the Quality of Mental Health Care in Europe) project.

Methods.

A total of eight study areas from European countries with different systems of care (Austria, England, Finland, France, Italy, Norway, Romania, Spain) were analysed using a standard open-access classification system (Description and Evaluation of Services for Long Term Care in Europe, DESDE-LTC). All publicly funded services universally accessible to adults (≥18 years) with a psychiatric disorder were coded. Care availability, diversity and capacity were compared across these eight local MHS.

Results.

The comparison of MHS revealed more community-oriented delivery systems in the areas of England (Hampshire) and Southern European countries (Verona – Italy and Girona – Spain). Community-oriented systems with a higher proportion of hospital care were identified in Austria (Industrieviertel) and Scandinavian countries (Sør-Trøndelag in Norway and Helsinki-Uusimaa in Finland), while Loiret (France) was considered as a predominantly hospital-based system. The MHS in Suceava (Romania) was still in transition to community care.

Conclusions.

There is a significant variation in care availability and capacity across MHS of local areas in Europe. This information is relevant for understanding the process of implementation of community-oriented mental health care in local areas. Standard comparison of care provision in local areas is important for context analysis and policy planning.
The lauric acid-activated signaling prompts apoptosis in cancer cells
Authors: Lappano Rosamaria , Sebastiani Anna , Cirillo Francesca , Rigiracciolo Damiano Cosimo , Galli Giulia Raffaella , Curcio Rosita , Malaguarnera Roberta , Belfiore Antonino , Cappello Anna Rita , Maggiolini Marcello
Published: September 2017

The saturated medium-chain fatty-acid lauric acid (LA) has been associated to certain health-promoting benefits of coconut oil intake, including the improvement of the quality of life in breast cancer patients during chemotherapy. As it concerns the potential to hamper tumor growth, LA was shown to elicit inhibitory effects only in colon cancer cells. Here, we provide novel insights regarding the molecular mechanisms through which LA triggers antiproliferative and pro-apoptotic effects in both breast and endometrial cancer cells. In particular, our results demonstrate that LA increases reactive oxygen species levels, stimulates the phosphorylation of EGFR, ERK and c-Jun and induces the expression of c-fos. In addition, our data evidence that LA via the Rho-associated kinase-mediated pathway promotes stress fiber formation, which exerts a main role in the morphological changes associated with apoptotic cell death. Next, we found that the increase of p21Cip1/WAF1 expression, which occurs upon LA exposure in a p53-independent manner, is involved in the apoptotic effects prompted by LA in both breast and endometrial cancer cells. Collectively, our findings may pave the way to better understand the anticancer action of LA, although additional studies are warranted to further corroborate its usefulness in more comprehensive therapeutic approaches.
Different developmental histories of beta-cells generate functional and proliferative heterogeneity during islet growth
Authors: Singh Sumeet Pal , Janjuha Sharan , Hartmann Theresa , Kayisoglu Özge , Konantz Judith , Birke Sarah , Murawala Priyanka , Alfar Ezzaldin Ahmed , Murata Kei , Eugster Anne , Tsuji Naoki , Morrissey Edward R. , Brand Michael , Ninov Nikolay
Published: September 2017

The proliferative and functional heterogeneity among seemingly uniform cells is a universal phenomenon. Identifying the underlying factors requires single-cell analysis of function and proliferation. Here we show that the pancreatic beta-cells in zebrafish exhibit different growth-promoting and functional properties, which in part reflect differences in the time elapsed since birth of the cells. Calcium imaging shows that the beta-cells in the embryonic islet become functional during early zebrafish development. At later stages, younger beta-cells join the islet following differentiation from post-embryonic progenitors. Notably, the older and younger beta-cells occupy different regions within the islet, which generates topological asymmetries in glucose responsiveness and proliferation. Specifically, the older beta-cells exhibit robust glucose responsiveness, whereas younger beta-cells are more proliferative but less functional. As the islet approaches its mature state, heterogeneity diminishes and beta-cells synchronize function and proliferation. Our work illustrates a dynamic model of heterogeneity based on evolving proliferative and functional beta-cell states.
RSV glycoprotein and genomic RNA dynamics reveal filament assembly prior to the plasma membrane
Authors: Vanover Daryll , Smith Daisy V. , Blanchard Emmeline L. , Alonas Eric , Kirschman Jonathan L. , Lifland Aaron W. , Zurla Chiara , Santangelo Philip J.
Published: September 2017

The human respiratory syncytial virus G protein plays an important role in the entry and assembly of filamentous virions. Here, we report the use of fluorescently labeled soybean agglutinin to selectively label the respiratory syncytial virus G protein in living cells without disrupting respiratory syncytial virus infectivity or filament formation and allowing for interrogations of respiratory syncytial virus virion assembly. Using this approach, we discovered that plasma membrane-bound respiratory syncytial virus G rapidly recycles from the membrane via clathrin-mediated endocytosis. This event is then followed by the dynamic formation of filamentous and branched respiratory syncytial virus particles, and assembly with genomic ribonucleoproteins and caveolae-associated vesicles prior to re-insertion into the plasma membrane. We demonstrate that these processes are halted by the disruption of microtubules and inhibition of molecular motors. Collectively, our results show that for respiratory syncytial virus assembly, viral filaments are produced and loaded with genomic RNA prior to insertion into the plasma membrane.
Stapled peptide inhibitors of RAB25 target context-specific phenotypes in cancer
Authors: Mitra Shreya , Montgomery Jeffrey E. , Kolar Matthew J. , Li Gang , Jeong Kang J. , Peng Bo , Verdine Gregory L. , Mills Gordon B. , Moellering Raymond E.
Published: September 2017

Recent evidence has established a role for the small GTPase RAB25, as well as related effector proteins, in enacting both pro-oncogenic and anti-oncogenic phenotypes in specific cellular contexts. Here we report the development of all-hydrocarbon stabilized peptides derived from the RAB-binding FIP-family of proteins to target RAB25. Relative to unmodified peptides, optimized stapled peptides exhibit increased structural stability, binding affinity, cell permeability, and inhibition of RAB25:FIP complex formation. Treatment of cancer cell lines in which RAB25 is pro-oncogenic with an optimized stapled peptide, RFP14, inhibits migration, and proliferation in a RAB25-dependent manner. In contrast, RFP14 treatment augments these phenotypes in breast cancer cells in which RAB25 is tumor suppressive. Transcriptional profiling identified significantly altered transcripts in response toRAB25expression, and treatment with RFP14 opposes this expression profile. These data validate the first cell-active chemical probes targeting RAB-family proteins and support the role of RAB25 in regulating context-specific oncogenic phenotypes.
miR-155 mediates arsenic trioxide resistance by activating Nrf2 and suppressing apoptosis in lung cancer cells
Authors: Gu Shiyan , Lai Yanhao , Chen Hongyu , Liu Yuan , Zhang Zunzhen
Published: September 2017

Arsenic trioxide (ATO) resistance is a challenging problem in chemotherapy. However, the underlying mechanisms remain to be elucidated. In this study, we identified a high level of expression of miR-155 in a human lung adenocarcinoma A549R cell line that is highly resistant to ATO. We showed that the high level of miR-155 was associated with increased levels of cell survival, colony formation, cell migration and decreased cellular apoptosis, and this was mediated by high levels of Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1) and a high ratio of Bcl-2/Bax. Overexpression of the miR-155 mimic in A549R cells resulted in increased levels of colony formation and cell migration as well as reduced apoptosis along with increased Nrf2, NQO1 and HO-1. In contrast, silencing of miR-155 expression with its inhibitor in the cells, significantly decreased the cellular levels of Nrf2, NQO1 and HO-1 as well as the ratio of Bcl-2/Bax. This subsequently reduced the level of colony formation and cell migration facilitating ATO-induced apoptosis. Our results indicate that miR-155 mediated ATO resistance by upregulating the Nrf2 signaling pathway, but downregulating cellular apoptosis in lung cancer cells. Our study provides new insights into miR-155-mediated ATO resistance in lung cancer cells.
Molecular insights into reproduction regulation of female Oriental River prawns Macrobrachium nipponense through comparative transcriptomic analysis
Authors: Qiao Hui , Fu Hongtuo , Xiong Yiwei , Jiang Sufei , zhang Wenyi , Sun Shengming , Jin Shubo , Gong Yongsheng , Wang Yabing , Shan Dongyan , Li Fei , Wu Yan
Published: September 2017

The oriental river prawn, Macrobrachium nipponense, is an important commercial aquaculture resource in China. During breeding season, short ovary maturation cycles of female prawns cause multi-generation reunions in ponds and affect the growth of females representing individual miniaturization (known as autumn -propagation). These reproductive characteristics pose problems for in large - scale farming. To date, the molecular mechanisms of reproduction regulation of M. nipponense remain unclear. To address this issue, we performed transcriptome sequencing and gene expression analyses of eyestalk and cerebral ganglia of female M. nipponense during breeding and non-breeding seasons. Differentially expressed gene enrichment analysis results revealed several important reproduction related terms and signaling pathways, such as “photoreceptor activity”, “structural constituent of cuticle” and “G-protein coupled receptor activity”. The following six key genes from the transcriptome were predicted to mediate environmental factors regulating reproduction of M. nipponense: neuroparsin, neuropeptide F II, orcokinin II, crustacean cardioactive peptide, pigment-dispersing hormone 3 and tachykinin. These results will contribute to a better understanding of the molecular mechanisms of reproduction of oriental river prawns. Further detailed functional analyses of the candidate reproduction regulation related neuropeptides are needed to shed light on the mechanisms of reproduction of crustacean.
Identification of a specific agonist of human TAS2R14 from Radix Bupleuri through virtual screening, functional evaluation and binding studies
Authors: Zhang Yuxin , Wang Xing , Li Xi , Peng Sha , Wang Shifeng , Huang Christopher Z. , Huang Corine Z. , Zhang Qiao , Li Dai , Jiang Jun , Ouyang Qin , Zhang Yanling , Li Shiyou , Qiao Yanjiang
Published: September 2017

Bitter taste receptors (TAS2Rs) have attracted a great deal of interest because of their recently described bronchodilator and anti-inflammatory properties. The aim of this study was to identify natural direct TAS2R14 agonists from Radix Bupleuri that can inhibit mast cell degranulation. A ligand-based virtual screening was conducted on a library of chemicals contained in compositions of Radix Bupleuri, and these analyses were followed by cell-based functional validation through a HEK293-TAS2R14-G16gust44 cell line and IgE-induced mast cell degranulation assays, respectively. Saikosaponin b (SSb) was confirmed for the first time to be a specific agonist of TAS2R14 and had an EC50 value of 4.9 μM. A molecular docking study showed that SSb could directly bind to a TAS2R14 model through H-bond interactions with Arg160, Ser170 and Glu259. Moreover, SSb showed the ability to inhibit IgE-induced mast cell degranulation, as measured with a β-hexosaminidase release model and real-time cell analysis (RTCA). In a cytotoxicity bioassay, SSb showed no significant cytotoxicity to HEK293 cells within 24 hours. This study demonstrated that SSb is a direct TAS2R14 agonist that inhibit IgE-induced mast cell degranulation. Although the target and in vitro bioactivity of SSb were revealed in this study, it still need in vivo study to further verify the anti-asthma activity of SSb.
GPNMB Induces BiP Expression by Enhancing Splicing of BiP Pre-mRNA during the Endoplasmic Reticulum Stress Response
Authors: Noda Yasuhiro , Tsuruma Kazuhiro , Takata Masafumi , Ishisaka Mitsue , Tanaka Hirotaka , Nakano Yusuke , Nagahara Yuki , Shimazawa Masamitsu , Hara Hideaki
Published: September 2017

Glycoprotein nonmetastatic melanoma protein B (GPNMB) has a neuroprotective effect against neuronal cell death caused by the accumulation of abnormal mutated proteins. It is known that the accumulation of pathological proteins induces endoplasmic-reticulum (ER) stress leading to cell damage. The aim of this study was to determine the role of GPNMB in the ER stress response. GPNMB was greatly up-regulated by thapsigargin-induced ER stress. Under the ER stress conditions, GPNMB relocated to the nucleus and specifically up-regulated expression of BiP at the mRNA level by promoting the BiP pre-mRNA splicing, not through the pathways initiated by the three major transducers of the unfolded protein response: IRE1, PERK, and ATF6. Furthermore, we found that the protein level of BiP and the infarction were increased and attenuated, respectively, in Gpnmb-transgenic mice after occlusion of the middle cerebral artery, in comparison with wild-type mice. Thus, our findings indicate that GPNMB enhances the BiP expression by promoting the splicing (thereby preventing cell death caused by ER stress) and could be a therapeutic target in ER stress-related disorders.
Pore formation in lipid membrane I: Continuous reversible trajectory from intact bilayer through hydrophobic defect to transversal pore
Authors: Akimov Sergey A. , Volynsky Pavel E. , Galimzyanov Timur R. , Kuzmin Peter I. , Pavlov Konstantin V. , Batishchev Oleg V.
Published: September 2017

Lipid membranes serve as effective barriers allowing cells to maintain internal composition differing from that of extracellular medium. Membrane permeation, both natural and artificial, can take place via appearance of transversal pores. The rearrangements of lipids leading to pore formation in the intact membrane are not yet understood in details. We applied continuum elasticity theory to obtain continuous trajectory of pore formation and closure, and analyzed molecular dynamics trajectories of pre-formed pore reseal. We hypothesized that a transversal pore is preceded by a hydrophobic defect: intermediate structure spanning through the membrane, the side walls of which are partially aligned by lipid tails. This prediction was confirmed by our molecular dynamics simulations. Conversion of the hydrophobic defect into the hydrophilic pore required surmounting some energy barrier. A metastable state was found for the hydrophilic pore at the radius of a few nanometers. The dependence of the energy on radius was approximately quadratic for hydrophobic defect and small hydrophilic pore, while for large radii it depended on the radius linearly. The pore energy related to its perimeter, line tension, thus depends of the pore radius. Calculated values of the line tension for large pores were in quantitative agreement with available experimental data.
Estrogenic vascular effects are diminished by chronological aging
Authors: Nicholson Christopher J. , Sweeney Michèle , Robson Stephen C. , Taggart Michael J.
Published: September 2017

The beneficial role of estrogen in the vascular system may be due, in part, through reduction of peripheral vascular resistance. The use of estrogen therapy to prevent cardiovascular disease in post-menopausal women remains contentious. This study investigated the influence of aging and the menopause on the acute vasodilatory effects of estrogen using ex vivo human and murine resistance arteries. Vessels were obtained from young (2.9 ± 0.1 months) and aged (24.2 ± 0.1 and 28.9 ± 0.3 months) female mice and pre- (42.3 ± 0.5 years) and post-menopausal (61.9 ± 0.9 years) women. Aging was associated with profound structural alterations of murine uterine arteries, including the occurrence of outward hypertrophic remodeling and increased stiffness. Endothelial and smooth muscle function were diminished in uterine (and tail) arteries from aged mice and post-menopausal women. The acute vasodilatory effects of 17β-estradiol (non-specific estrogen receptor (ER) agonist), PPT (ERα-specific agonist) and DPN (ERβ-specific agonist) on resistance arteries were attenuated by aging and the menopause. However, the impairment of estrogenic relaxation was evident after the occurrence of age-related endothelial dysfunction and diminished distensibility. The data indicate, therefore, that chronological resistance arterial aging is a prominent factor leading to weakened vasodilatory action of estrogenic compounds.
Dietary teasaponin ameliorates alteration of gut microbiota and cognitive decline in diet-induced obese mice
Authors: Wang Sen , Huang Xu-Feng , Zhang Peng , Newell Kelly A. , Wang Hongqin , Zheng Kuiyang , Yu Yinghua
Published: September 2017

A high-fat (HF) diet alters gut microbiota and promotes obesity related inflammation and cognitive impairment. Teasaponin is the major active component of tea, and has been associated with anti-inflammatory effects and improved microbiota composition. However, the potential protective effects of teasaponin, against HF diet-induced obesity and its associated alteration of gut microbiota, inflammation and cognitive decline have not been studied. In this study, obesity was induced in C57BL/6 J male mice by feeding a HF diet for 8 weeks, followed by treatment with oral teasaponin (0.5%) mixed in HF diet for a further 6 weeks. Teasaponin treatment prevented the HF diet-induced recognition memory impairment and improved neuroinflammation, gliosis and brain-derived neurotrophic factor (BDNF) deficits in the hippocampus. Furthermore, teasaponin attenuated the HF diet-induced endotoxemia, pro-inflammatory macrophage accumulation in the colon and gut microbiota alterations. Teasaponin also improved glucose tolerance and reduced body weight gain in HF diet-induced obese mice. The behavioral and neurochemical improvements suggest that teasaponin could limit unfavorable gut microbiota alterations and cognitive decline in HF diet-induced obesity.
Differential Proteomics Identifies Reticulocalbin-3 as a Novel Negative Mediator of Collagen Production in Human Cardiac Fibroblasts
Authors: Martínez-Martínez Ernesto , Ibarrola Jaime , Fernández-Celis Amaya , Santamaria Enrique , Fernández-Irigoyen Joaquín , Rossignol Patrick , Jaisser Frederic , López-Andrés Natalia
Published: September 2017

Cardiac fibrosis is characterized by an excessive accumulation of extracellular matrix components, including collagens. Galectin-3 (Gal-3) and Cardiotrophin-1 (CT-1) are two profibrotic molecules that mediate Aldosterone (Aldo)-induced cardiac fibrosis. However the underlying mechanisms are not well defined. Our aim is to characterize changes in the proteome of human cardiac fibroblasts treated with Aldo, Gal-3 or CT-1 to identify new common proteins that might be new therapeutic targets in cardiac fibrosis. Using a quantitative proteomic approach in human cardiac fibroblasts, our results show that Aldo, Gal-3 and CT-1 modified the expression of 30, 17 and 89 proteins respectively, being common the reticulocalbin (RCN) family members. RCN-3 down-regulation triggered by Aldo, Gal-3 and CT-1 was verified. Treatment with recombinant RCN-3 decreased collagens expression in human cardiac fibroblasts through Akt phosphorylation. Interestingly, CRISPR/Cas9-mediated activation of RCN-3 decreased collagen production in human cardiac fibroblasts. In addition, recombinant RCN-3 blocked the profibrotic effects of Aldo, Gal-3 and CT-1. Interestingly, RCN-3 blunted the increase in collagens expression induced by other profibrotic stimuli, angiotensin II, in human cardiac fibroblasts. Our results suggest that RCN-3 emerges as a new potential negative regulator of collagen production and could represent a therapeutic target in the context of cardiac fibrosis.
Determination of extracellular matrix collagen fibril architectures and pathological remodeling by polarization dependent second harmonic microscopy
Authors: Rouède Denis , Schaub Emmanuel , Bellanger Jean-Jacques , Ezan Frédéric , Scimeca Jean-Claude , Baffet Georges , Tiaho François
Published: September 2017

Polarization dependence second harmonic generation (P-SHG) microscopy is gaining increase popularity for in situ quantification of fibrillar protein architectures. In this report, we combine P-SHG microscopy, new linear least square (LLS) fitting and modeling to determine and convert the complex second-order non-linear optical anisotropy parameter ρ of several collagen rich tissues into a simple geometric organization of collagen fibrils. Modeling integrates a priori knowledge of polyhelical organization of collagen molecule polymers forming fibrils and bundles of fibrils as well as Poisson photonic shot noise of the detection system. The results, which accurately predict the known sub-microscopic hierarchical organization of collagen fibrils in several tissues, suggest that they can be subdivided into three classes according to their microscopic and macroscopic hierarchical organization of collagen fibrils. They also show, for the first time to our knowledge, intrahepatic spatial discrimination between genuine fibrotic and non-fibrotic vessels. CCl4-treated livers are characterized by an increase in the percentage of fibrotic vessels and their remodeling involves peri-portal compaction and alignment of collagen fibrils that should contribute to portal hypertension. This integrated P-SHG image analysis method is a powerful tool that should open new avenue for the determination of pathophysiological and chemo-mechanical cues impacting collagen fibrils organization.
Brain Inflammation, Blood Brain Barrier dysfunction and Neuronal Synaptophysin Decrease after Inhalation Exposure to Titanium Dioxide Nano-aerosol in Aging Rats
Authors: Disdier Clémence , Chalansonnet Monique , Gagnaire François , Gaté Laurent , Cosnier Frédéric , Devoy Jérôme , Saba Wadad , Lund Amie K. , Brun Emilie , Mabondzo Aloïse
Published: September 2017

Notwithstanding potential neurotoxicity of inhaled titanium dioxide nanoparticles (TiO2 NPs), the toxicokinetics and consequences on blood-brain barrier (BBB) function remain poorly characterized. To improve risk assessment, we need to evaluate the impact on BBB under realistic environmental conditions and take into account vulnerability status such as age. 12–13 week and 19-month-old male rats were exposed by inhalation to 10 mg/m3 of TiO2 nano-aerosol (6 hrs/day, 5 day/week, for 4 weeks). We showed an age-dependent modulation of BBB integrity parameters suggesting increased BBB permeability in aging rats. This alteration was associated with a significant increase of cytokines/chemokines in the brain, including interleukin-1β, interferon-γ, and fractalkine as well as a decreased expression of synaptophysin, a neuronal activity marker. These observations, in absence of detectable titanium in the brain suggest that CNS-related effects are mediated by systemic-pathway. Moreover, observations in terms of BBB permeability and brain inflammation underline age susceptibility. Even if TiO2 NPs were not evidenced in the brain, we observed an association between the exposure to TiO2 NPs and the dysregulation of BBB physiology associated with neuroinflammation and decreased expression of neuronal activity marker, which was further exacerbated in the brain of aged animal’s.
Genetic screening confirms heterozygous mutations in ACAN as a major cause of idiopathic short stature
Authors: Hauer Nadine N. , Sticht Heinrich , Boppudi Sangamitra , Büttner Christian , Kraus Cornelia , Trautmann Udo , Zenker Martin , Zweier Christiane , Wiesener Antje , Jamra Rami Abou , Wieczorek Dagmar , Kelkel Jaqueline , Jung Anna-Maria , Uebe Steffen , Ekici Arif. B , Rohrer Tilman , Reis André , Dörr Helmuth-Günther , Thiel Christian T.
Published: September 2017

Short stature is a common pediatric disorder affecting 3% of the population. However, the clinical variability and genetic heterogeneity prevents the identification of the underlying cause in about 80% of the patients. Recently, heterozygous mutations in the ACAN gene coding for the proteoglycan aggrecan, a main component of the cartilage matrix, were associated with idiopathic short stature. To ascertain the prevalence of ACAN mutations and broaden the phenotypic spectrum in patients with idiopathic short stature we performed sequence analyses in 428 families. We identified heterozygous nonsense mutations in four and potentially disease-causing missense variants in two families (1.4%). These patients presented with a mean of −3.2 SDS and some suggestive clinical characteristics. The results suggest heterozygous mutations in ACAN as a common cause of isolated as well as inherited idiopathic short stature.
UbasM: An effective balanced optical clearing method for intact biomedical imaging
Authors: Chen Lingling , Li Guiye , Li Yamin , Li Yingchao , Zhu Haiou , Tang Li , French Paul , McGinty James , Ruan Shuangchen
Published: September 2017

Optical clearing methods can facilitate deep optical imaging in biological tissue by reducing light scattering and this has enabled accurate three-dimensional signal visualization and quantification of complex biological structures. Unfortunately, existing optical clearing approaches present a compromise between maximizing clearing capability, the preservation of fluorescent protein emission and membrane integrity and the speed of sample processing – with the latter typically requiring weeks for cm scale tissue samples. To address this challenge, we present a new, convenient, aqueous optical clearing agent, termed UbasM: Urea-Based Amino-Sugar Mixture, that rapidly renders fixed tissue samples highly transparent and reliably preserves emission from fluorescent proteins and lipophilic dyes in membrane integrity preserved tissues. UbasM is simple, inexpensive, reproducible and compatible with all labeling methods that we have encountered. It can enable convenient, volumetric imaging of tissue up to the scale of whole adult mouse organs and should be useful for a wide range of light microscopy and tomography techniques applied to biomedical research, especially the study on organism-level systems biology at multiple levels.
Expression and Differential Responsiveness of Central Nervous System Glial Cell Populations to the Acute Phase Protein Serum Amyloid A
Authors: Barbierato Massimo , Borri Mila , Facci Laura , Zusso Morena , Skaper Stephen D. , Giusti Pietro
Published: September 2017

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves hepatic production of acute-phase proteins, including serum amyloid A (SAA). Extrahepatically, SAA immunoreactivity is found in axonal myelin sheaths of cortex in Alzheimer’s disease and multiple sclerosis (MS), although its cellular origin is unclear. We examined the responses of cultured rat cortical astrocytes, microglia and oligodendrocyte precursor cells (OPCs) to master pro-inflammatory cytokine tumour necrosis factor (TNF)-α and lipopolysaccaride (LPS). TNF-α time-dependently increasedSaa1(but notSaa3) mRNA expression in purified microglia, enriched astrocytes, and OPCs (as did LPS for microglia and astrocytes). Astrocytes depleted of microglia were markedly less responsive to TNF-α and LPS, even after re-addition of microglia. Microglia and enriched astrocytes showed complementarySaa1expression profiles following TNF-α or LPS challenge, being higher in microglia with TNF-α and higher in astrocytes with LPS. Recombinant human apo-SAA stimulated production of both inflammatory mediators and its own mRNA in microglia and enriched, but not microglia-depleted astrocytes. Co-ultramicronized palmitoylethanolamide/luteolin, an established anti-inflammatory/ neuroprotective agent, reducedSaa1expression in OPCs subjected to TNF-α treatment. These last data, together with past findings suggest that co-ultramicronized palmitoylethanolamide/luteolin may be a novel approach in the treatment of inflammatory demyelinating disorders like MS.