bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of fluorescent dye substrates for functional characterization of ABC multidrug transporters at a single cell level
Authors: Nerada Zsuzsanna , Hegyi Zoltán , Szepesi Áron , Tóth Szilárd , Hegedüs Csilla , Várady György , Matula Zsolt , Homolya László , Sarkadi Balázs , Telbisz Ágnes 
Published: September 2016

AbstractABC multidrug transporters are key players in cancer multidrug resistance and in determining the ADME‐Tox properties of drugs and xenobiotics. The most sensitive and specific detection of these transporters is based on functional assays. Assessment of the transporter‐dependent reduction of cellular uptake of the fluorescent dyes, such as Hoechst 33342 (Ho) and more recently DyeCycle Violet (DCV), have been widely advocated for the characterization of both ABCB1 and ABCG2 multidrug transporters. Detailed comparison of these supravital DNA‐binding dyes revealed that DCV is less toxic to ABCG2‐ and ABCB1‐expressing cells than Ho. ATPase measurements imply that DCV and Ho are similarly handled by ABCB1, whereas ABCG2 seems to transport DVC more effectively. In addition, we have developed an image‐based high content microscopy screening method for simultaneous in situ measurement of the cellular activity and expression of the ABCG2 multidrug transporter. We demonstrated the applicability of this method for identifying ABCG2‐positive cells in heterogeneous cell population by a single dye uptake measurement. These results may promote multidrug transporter studies at a single cell level and allow the quantitative detection of clinically important drug‐resistant sub‐populations. © 2016 International Society for Advancement of Cytometry
Lifespan oxytocin signaling: Maturation, flexibility, and stability in newborn, adolescent, and aged brain
Authors: Sannino Sara , Chini Bice , Grinevich Valery 
Published: September 2016

ABSTRACTThe hypothalamic neuropeptide oxytocin (OT) is a forefront molecule among neuropeptides due to its pronounced prosocial effects and its potential use in socioemotional deficits that characterize the most prevalent neurodevelopmental and psychiatric disorders (autism spectrum disorders and schizophrenia). The effects of OT have been studied in young and adult subjects (either animals or humans), while the complete lifespan trajectories of OT system development and activity have been far less investigated. In this (mini) review, we will primarily focus on three temporal distinct periods of life—early postnatal period, puberty/adolescence, and elderly. We selected the neonatal period to discuss the role of OT in the switch of GABA action from excitation to inhibition in the first days after birth (in rodents), with potential implications in neurodevelopmental disorders. In the puberty/adolescence period, we consider of particular relevance the OT impact on drug consumption, stress and aggression. Finally, OT could potentially contribute to maintain social capacities of aged people and to ameliorate socially emotional deficits and symptoms of neurodegenerative diseases. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 158–168, 2017
Back to the drawing board: Understanding the complexity of hepatic innate lymphoid cells
Authors: Marotel Marie , Hasan Uzma , Viel Sébastien , Marçais Antoine , Walzer Thierry 
Published: September 2016

Recent studies of immune populations in nonlymphoid organs have highlighted the great diversity of the innate lymphoid system. It has also become apparent that mouse and human innate lymphoid cells (ILCs) have distinct phenotypes and properties. In this issue of the European Journal of Immunology, Harmon et al. [Eur. J. Immunol. 2016. 46: 2111–2120] characterized human hepatic NK‐cell subsets. The authors report that hepatic CD56bright NK cells resemble mouse liver ILC1s in that they express CXCR6 and have an immature phenotype. However, unlike mouse ILC1s, they express high levels of Eomes and low levels of T‐bet, and upon stimulation with tumor cells, secrete low amounts of cytokines. These unexpected findings further support the differences between human and mouse immune populations and prompt the study of the role of hepatic ILC subsets in immune responses.
Modulation of immune and antioxidant responses by azinphos-methyl in the freshwater mussel Diplodon chilensis challenged with Escherichia coli
Authors: Castro Juan Manuel , Bianchi Virginia Angélica , Pascual Mariano , Venturino Andrés , Luquet Carlos Marcelo 
Published: September 2016

Abstract

The aim of the present study was to characterize the immune response—total hemocyte number, cell type proportion, hemocyte viability, lysosomal membrane stability, phagocytic activity, cellular acid and alkaline phosphatase activity, and humoral bacteriolytic and phenoloxidase activity—­in Diplodon chilensis exposed to 0.2 mg/L of azinphos-methyl (AZM), using Escherichia coli as immunological and pro-oxidant challenges. In addition, glutathione-S-transferase and lipid peroxidation thiobarbituric acid reactive substances were analyzed in gill tissue. Mussels from an unpolluted site were treated for 3 d as follows: 1) experimental control; 2) solvent effects control (acetone 0.01%); 3) bacterial challenge effects control (E. coli, 5 cells/mL × 104 cells/mL); 4) pesticide effects control (AZM in acetone); 5) control for combined effects of solvent and bacterial challenge; and 6) exposed to AZM, then challenged with E. coli. The results showed increased granulocyte proportion and phagocytic activity. Partial reversion of deleterious effects of E. coli on lysosomal membranes was observed in mussels exposed to AZM and then challenged with E. coli. Total hemocyte number and humoral bacteriolytic activity were increased only by E. coli challenge. Acid phosphatase activity was increased by both E. coli and AZM, whereas the stimulating effect of E. coli on alkaline phosphatase activity was negatively modulated by AZM. Azinphos-methyl inhibited phenoloxidase activity regardless of the E. coli challenge. Gill glutathione-S-transferase activity was increased by E. coli treatment either alone or pretreated with acetone or AZM and by AZM alone. Thiobarbituric acid reactive substance levels were reduced by AZM alone or combined with the E. coli challenge and by acetone followed by the E. coli challenge. Both acetone and AZM seem to be important modulators of immune and antioxidant responses in D. chilensis. Environ Toxicol Chem 2017;36:1785–1794. © 2016 SETAC
Sensitivity of lake sturgeon (Acipenser fulvescens) early life stages to 2,3,7,8-tetrachlorodibenzo-P-dioxin and 3,3′,4,4′,5-pentachlorobiphenyl
Authors: Tillitt Donald E. , Buckler Justin A. , Nicks Diane K. , Candrl James S. , Claunch Rachel A. , Gale Robert W. , Puglis Holly J. , Little Edward E. , Linbo Tiffany L. , Baker Mary 
Published: September 2016

Abstract

The aquatic food web of the Great Lakes has been contaminated with polychlorinated biphenyls (PCBs) since the mid-20th century. Threats of PCB exposures to long-lived species of fish, such as lake sturgeon (Acipenser fulvescens), have been uncertain because of a lack of information on the relative sensitivity of the species. The objective of the present study was to evaluate the sensitivity of early–life stage lake sturgeon to 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure. Mortality, growth, morphological and tissue pathologies, swimming performance, and activity levels were used as assessment endpoints. Pericardial and yolk sac edema, tubular heart, yolk sac hemorrhaging, and small size were the most commonly observed pathologies in both TCDD and PCB-126 exposures, beginning as early as 4 d postfertilization, with many of these pathologies occurring in a dose-dependent manner. Median lethal doses for PCB-126 and TCDD in lake sturgeon were 5.4 ng/g egg (95% confidence interval, 3.9–7.4 ng/g egg) and 0.61 ng/g egg (0.47–0.82 ng/g egg), respectively. The resulting relative potency factor for PCB-126 (0.11) was greater than the World Health Organization estimate for fish (toxic equivalency factor = 0.005), suggesting that current risk assessments may underestimate PCB toxicity toward lake sturgeon. Swimming activity and endurance were reduced in lake sturgeon survivors from the median lethal doses at 60 d postfertilization. Threshold and median toxicity values indicate that lake sturgeon, like other Acipenser species, are more sensitive to PCB and TCDD than the other genus of sturgeon, Scaphirhynchus, found in North America. Indeed, lake sturgeon populations in the Great Lakes and elsewhere are susceptible to PCB/TCDD-induced developmental toxicity in embryos and reductions in swimming performance. Environ Toxicol Chem 2017;36:988–998. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
Groundwater—Surface waters interactions at slope and catchment scales: implications for landsliding in clay‐rich slopes
Authors: Marc Vincent , Bertrand Catherine , Malet Jean‐Philippe , Carry Nicolas , Simler Roland , Cervi Federico 
Published: September 2016

AbstractUnderstanding water infiltration and transfer in soft‐clay shales slopes is an important scientific issue, especially for landsliding. Geochemical investigations are carried out at the Super‐Sauze and Draix‐Laval landslides, both developed in the Callovo‐Oxfordian black marls, with the objective to define the origin of the groundwater. In situ investigations, soil leaching experiments and geochemical modeling are combined to identify the boundaries of the hydrological systems. At Super‐Sauze, the observations indicate that an external water flow occurs in the upper part of the landslide at the contact between the weathered black marls and the overlying formations, or at the landslide basement through a fault network. Such external origin of water is not observed at the local scale of the Draix‐Laval landslide but is detected at the catchment scale with the influence of deep waters in the streamwater quality of low river flows. Hydrogeological conceptual models are proposed emphasizing the role of the interactions between local (slope) and regional (catchment) flow systems. The observations suggest that this situation is a common case in the Alpine area. Expected consequences of the regional flows on slope stability are discussed in term of rise of pore water pressures and physicochemical weathering of the clay shales.
Assessing the relevance of ecotoxicological studies for regulatory decision making
Authors: Rudén Christina , Adams Julie , Ågerstrand Marlene , Brock Theo CM , Poulsen Veronique , Schlekat Christian E , Wheeler James R , Henry Tala R 
Published: September 2016

Abstract

Regulatory policies in many parts of the world recognize either the utility of or the mandate that all available studies be considered in environmental or ecological hazard and risk assessment (ERA) of chemicals, including studies from the peer-reviewed literature. Consequently, a vast array of different studies and data types need to be considered. The first steps in the evaluation process involve determining whether the study is relevant to the ERA and sufficiently reliable. Relevance evaluation is typically performed using existing guidance but involves application of “expert judgment” by risk assessors. In the present paper, we review published guidance for relevance evaluation and, on the basis of the practical experience within the group of authors, we identify additional aspects and further develop already proposed aspects that should be considered when conducting a relevance assessment for ecotoxicological studies. From a regulatory point of view, the overarching key aspect of relevance concerns the ability to directly or indirectly use the study in ERA with the purpose of addressing specific protection goals and ultimately regulatory decision making. Because ERA schemes are based on the appropriate linking of exposure and effect estimates, important features of ecotoxicological studies relate to exposure relevance and biological relevance. Exposure relevance addresses the representativeness of the test substance, environmental exposure media, and exposure regime. Biological relevance deals with the environmental significance of the test organism and the endpoints selected, the ecological realism of the test conditions simulated in the study, as well as a mechanistic link of treatment-related effects for endpoints to the protection goal identified in the ERA. In addition, uncertainties associated with relevance should be considered in the assessment. A systematic and transparent assessment of relevance is needed for regulatory decision making. The relevance aspects also need to be considered by scientists when designing, performing, and reporting ecotoxicological studies to facilitate their use in ERA. Integr Environ Assess Manag 2017;13:652–663. © 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)

Key Points
Relevance assessment of ecotoxicological studies is required to ensure appropriate use in hazard and risk assessment of chemicals. Structured and systematic evaluation processes are preferred to promote reproducibility and transparency. Relevance assessment consists of overarching regulatory relevance and associated aspects concerning exposure and biological components. The examples provided may inform and improve guidance for relevance assessment of ecotoxicological studies for use in regulatory decision making.
Epstein‐Barr virus mRNA profiles and viral DNA methylation status in nasopharyngeal brushings from nasopharyngeal carcinoma patients reflect tumor origin
Authors: Ramayanti Octavia , Juwana Hedy , Verkuijlen Sandra A.M.W. , Adham Marlinda , Pegtel Michiel D. , Greijer Astrid E. , Middeldorp Jaap M. 
Published: September 2016

Undifferentiated nasopharyngeal carcinoma (NPC) is 100% associated with Epstein‐Barr virus (EBV) as oncogenic driver. NPC is often diagnosed late due to initial vague complaints and obscured location. Prior studies suggest that measurement of EBV DNA load and RNA transcripts in nasopharyngeal (NP) brushings is useful for minimally invasive NPC diagnosis. However, whether these EBV markers relate to local virus replication or reflect tumor origin remains to be demonstrated. To resolve this, we analysed EBV‐DNA characteristics and quantified latent and lytic viral RNA transcripts in NP brushings and matching frozen NP‐biopsy specimens from patients suspected of having NPC.We observed non‐fragmented and Cp‐promotor methylated EBV‐DNA in both NP brushings and biopsies suggestive of tumor origin. Using quantitative RT‐PCR we determined expression levels of 7 critical latent (EBER1, Qp‐EBNA1, EBNA2, BART, LMP1, LMP2, BARF1) and 5 lytic (Zta, Rta, TK, PK and VCA‐p18) RNA transcripts. Although latent and early lytic RNA transcripts were frequently detected in conjunction with high EBV viral load, in both brushings and biopsies the latent transcripts prevailed and reflected a typical NPC‐associated latency‐II transcription profile without EBNA2. Late lytic RNA transcripts were rare and detected at low levels mainly in NP brushings, suggestive of abortive viral reactivation rather than complete virus replication. EBV‐IgA serology (EBNA1, VCA, Zta) did not correlate to the level of viral reactivation in situ.Overall, viral RNA profiling, DNA fragmentation and methylation analysis in NP brushings and parallel biopsies indicate that NP brush sampling provides a true and robust indicator of NPC tumor presence.
Exposure to cyclic volatile methylsiloxanes (cVMS) causes anchorage‐independent growth and reduction of BRCA1 in non‐transformed human breast epithelial cells
Authors: Farasani Abdullah , Darbre Philippa D. 
Published: September 2016

AbstractDermal absorption of components of personal care products (PCPs) may contribute to breast cancer development. Cyclic volatile methylsiloxanes (cVMS) are used widely in the formulation of PCPs, and their presence has been recently detected in human blood. The objectives of this study were to investigate any genotoxic effects after short‐ (1 week) or longer‐term (30 weeks) exposure to hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4) or decamethylcyclopentasiloxane (D5) in MCF‐10 A and MCF‐10F immortalized non‐transformed human breast epithelial cells. Genotoxic effects were assessed by an ability of cells to grow in suspension culture, from DNA damage measured by comet assays, and from a reduction in levels of DNA repair proteins measured by RT‐PCR and western immunoblotting. Dose‐dependent anchorage‐independent growth in methocel culture was observed after exposure to D3 (10−13 M–10−5 M) and D4/D5 (10−9 M–10−5 M). DNA damage was measured by the comet assay after 1‐h exposure to D3 (10−6 M–10−5 M) and D4 (10−5 M). BRCA1 mRNA and BRCA1 protein levels were reduced after 30‐week exposure to 10−5 M D4 and D5 in both cell lines. Reduced levels of mRNAs for other DNA repair proteins (BRCA2, ATM, ATR, CHK1 and CHK2) were also observed after exposure to 10−5 M D5 in both cell lines, and some reductions after exposure to D3 and D4. If cVMS can not only enable anchorage‐independent growth of non‐transformed breast epithelial cells and damage DNA, but also compromise DNA repair systems, then there is the potential for them to impact on breast carcinogenesis. Further risk assessment now requires information concerning the extent to which cVMS may be present in human breast tissues. Copyright © 2016 John Wiley & Sons, Ltd.
Comparative genotoxicity of silver nanoparticles in human liver HepG2 and lung epithelial A549 cells
Authors: Wang J. , Che B. , Zhang L. W. , Dong G. , Luo Q. , Xin L. 
Published: September 2016

AbstractWith the rapid expanding of human exposure to silver nanoparticles (AgNPs), genotoxicity screening of nanosilver is necessary to ensure consumer safety. Here, we assessed one key DNA damage responsive pathway activated by GADD45a gene after 24 h of AgNPs exposure in stable luciferase reporter cell systems based on two widely used in vitro cell models, human liver HepG2 and lung epithelial A549 cells. The comet assay and micronucleus test were also conducted to confirm the genetic damage induced by AgNPs. Our results showed that AgNPs produced a strong dose‐dependent increase in transcriptional activation of GADD45a promoter indicated by luciferase activity accompanying by the significant decreases in cell viability. Surprisingly, in HepG2‐luciferase cells, the relative luciferase activity was greater than 4.5× the control level after being treated with 200 μg ml–1 AgNPs. These results were generally in line with the positive and dose‐dependent responses in cytotoxicity, DNA strand breaks indicated by Olive tail moment, tail DNA (%) and tail length, and chromosome damage indicated by induction of micronuclei, nucleoplasmic bridges, and nuclear buds. Additionally, compared with the A549‐luciferase cells, the HepG2‐luciferase cells seemed to be more susceptible to AgNPs as higher levels of genotoxicity were induced. We concluded that our GADD45a promoter‐driven luciferase reporter gene cell system, together with the comet assay and micronucleus test, can be used as valuable tools for rapid screening of genotoxic potential of nanosilver. Copyright © 2016 John Wiley & Sons, Ltd.
Shaping photomechanical effects in tissue ablation using 355 nm laser pulses
Authors: Herzog Amir , Steinberg Idan , Ishaaya Amiel A. 
Published: September 2016

We investigate the influence of the cladding diameter of an optical delivery fiber on the ablation dynamics of porcine aorta immersed in tetracycline antibiotic solution using 355 nm nanosecond pulses. We manipulate the pressure transients by enforcing a rear rigid interface (applied by an enlargement of the cladding diameter) to the ablated area, which leads to enhanced ablation efficiency along with a reduction in tissue disruption effects. Numerical simulations, based on the finite elements method, are used to study the propagation of the pressure transients within the suggested scheme. Ultrasonic transducers are used for measuring the increased pressure in front of the fiber's facet and the reduced pressure at the fiber's circumference in the presence of large diameter cladding. The increase and decrease are both found to be by a factor of ˜1.8. The width of the cavitation bubble is measured by high‐speed photography. An enlargement of 13.8% is demonstrated, at the expense of backward expansion along the fiber's axis. A histopathological in vitro study demonstrates an average enhancement of 12.27% in the diameter of the ablated crater, as well as significant reduction in the disruption effects. Our study sheds light on the potential to improve the ablation efficiency without additional energy cost, along with attaining improved safety for interventional medical procedures.
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Solubilized extracellular matrix bioscaffolds derived from diverse source tissues differentially influence macrophage phenotype
Authors: Dziki Jenna L. , Wang Derek S. , Pineda Catalina , Sicari Brian M. , Rausch Theresa , Badylak Stephen F. 
Published: September 2016

AbstractThe host response to biomaterials is a critical determinant of their success or failure in tissue‐repair applications. Macrophages are among the first responders in the host response to biomaterials and have been shown to be predictors of downstream tissue remodeling events. Biomaterials composed of mammalian extracellular matrix (ECM) in particular have been shown to promote distinctive and constructive remodeling outcomes when compared to their synthetic counterparts, a property that has been largely attributed to their ability to modulate the host macrophage response. ECM bioscaffolds are prepared by decellularizing source tissues such as dermis and small intestinal submucosa. The differential ability of such scaffolds to influence macrophage behavior has not been determined. The present study determines the effects of ECM bioscaffolds derived from eight different source tissues upon macrophage surface marker expression, protein content, phagocytic capability, metabolism, and antimicrobial activity. The results show that macrophages exposed to small intestinal submucosa (SIS), urinary bladder matrix (UBM), brain ECM (bECM), esophageal ECM (eECM), and colonic ECM (coECM) express a predominant M2‐like macrophage phenotype, which is pro‐remodeling and anti‐inflammatory (iNOS−/Fizz1+/CD206+). In contrast, macrophage exposure to dermal ECM resulted in a predominant M1‐like, pro‐inflammatory phenotype (iNOS+/Fizz1−/CD206−), whereas liver ECM (LECM) and skeletal muscle ECM (mECM) did not significantly change the expression of these markers. All solubilized ECM bioscaffold treatments resulted in an increased macrophage antimicrobial activity, but no differences were evident in macrophage phagocytic capabilities, and macrophage metabolism was decreased following exposure to UBM, bECM, mECM, coECM, and dECM. The present work could have important implications when considering the macrophage response following ECM implantation for site‐appropriate tissue remodeling. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 138–147, 2017.