bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic regulation of NLRP3
Authors: Hughes Mark M. , O'Neill Luke A.J. 
Published: December 2017

SummaryA shift in our understanding of macrophage biology has come about as a result of recent discoveries in the area of metabolic reprogramming of macrophages. The NLRP3 inflammasome drives the activation of caspase‐1, leading to the production of IL‐1β, IL‐18, and a type of cell death termed pyroptosis. The NLRP3 inflammasome has been shown to sense metabolites such as palmitate, uric acid, and cholesterol crystals and is inhibited by ketone bodies produced during metabolic flux. The NLRP3 inflammasome has also been shown to be regulated by mitochondrial reactive oxygen species and components of glycolysis, such as Hexokinase. Here, we review these findings and discuss their importance for inflammation and furthermore discuss potential therapeutic benefits of targeting NLRP3.
Autophagy limits activation of the inflammasomes
Authors: Takahama Michihiro , Akira Shizuo , Saitoh Tatsuya 
Published: December 2017

SummaryInflammasomes are multiprotein complexes that control the maturation and production of interleukin‐1 family members and play crucial roles in host defense against pathogens. However, dysregulated activation of inflammasomes is associated with intense inflammation, leading to the development of inflammatory diseases. Therefore, inflammasomes must be activated at a proper strength to protect against infection and avoid tissue damage. Recent studies have highlighted the cross‐talk between inflammasome activation and autophagy, the cellular machinery associated with the degradation of intracellular components and maintenance of cellular homeostasis. Notably, deficiencies in autophagy‐related proteins induce the aberrant activation of inflammasomes, causing severe tissue damage. In contrast, autophagy inducers ameliorate symptoms of inflammasome‐related diseases. In this review, we discuss recent advances in the involvement of autophagy in regulating inflammasomes activation and in the development of inflammatory diseases.
IL‐1 and IL‐1 regulatory pathways in cancer progression and therapy
Authors: Mantovani Alberto , Barajon Isabella , Garlanda Cecilia 
Published: December 2017

SummaryInflammation is an important component of the tumor microenvironment. IL‐1 is an inflammatory cytokine which plays a key role in carcinogenesis and tumor progression. IL‐1 is subject to regulation by components of the IL‐1 and IL‐1 receptor (ILR) families. Negative regulators include a decoy receptor (IL‐1R2), receptor antagonists (IL‐1Ra), IL‐1R8, and anti‐inflammatory IL‐37. IL‐1 acts at different levels in tumor initiation and progression, including driving chronic non‐resolving inflammation, tumor angiogenesis, activation of the IL‐17 pathway, induction of myeloid‐derived suppressor cells (MDSC) and macrophage recruitment, invasion and metastasis. Based on initial clinical results, the translation potential of IL‐1 targeting deserves extensive analysis.
Interleukin‐18: Biological properties and role in disease pathogenesis
Authors: Kaplanski Gilles 
Published: December 2017

SummaryInitially described as an interferon (IFN)γ‐inducing factor, interleukin (IL)‐18 is indeed involved in Th1 and NK cell activation, but also in Th2, IL‐17‐producing γδ T cells and macrophage activation. IL‐18, a member of the IL‐1 family, is similar to IL‐1β for being processed by caspase 1 to an 18 kDa‐biologically active mature form. IL‐18 binds to its specific receptor (IL‐18Rα, also known as IL‐1R7) forming a low affinity ligand chain. This is followed by recruitment of the IL‐18Rβ chain. IL‐18 then uses the same signaling pathway as IL‐1 to activate NF‐kB and induce inflammatory mediators such as adhesion molecules, chemokines and Fas ligand. IL‐18 also binds to the circulating high affinity IL‐18 binding protein (BP), such as only unbound free IL‐18 is active. IL‐18Rα may also bind IL‐37, another member of the IL‐1 family, but in association with the negative signaling chain termed IL‐1R8, which transduces an anti‐inflammatory signal. IL‐18BP also binds IL‐37 and this acts as a sink for the anti‐inflammatory properties of IL‐37. There is now ample evidence for a role of IL‐18 in various infectious, metabolic or inflammatory diseases such as influenza virus infection, atheroma, myocardial infarction, chronic obstructive pulmonary disease, or Crohn's disease. However, IL‐18 plays a very specific role in the pathogenesis of hemophagocytic syndromes (HS) also termed Macrophage Activation Syndrome. In children affected by NLRC4 gain‐of‐function mutations, IL‐18 circulates in the range of tens of nanograms/mL. HS is treated with the IL‐1 Receptor antagonist (anakinra) but also specifically with IL‐18BP. Systemic juvenile idiopathic arthritis or adult‐onset Still's disease are also characterized by high serum IL‐18 concentrations and are treated by IL‐18BP.
The AIM2 inflammasome: Sensor of pathogens and cellular perturbations
Authors: Lugrin Jérôme , Martinon Fabio 
Published: December 2017

SummaryRecognition of pathogens and altered self must be efficient and highly specific to orchestrate appropriate responses while limiting excessive inflammation and autoimmune reaction to normal self. AIM2 is a member of innate immune sensors that detects the presence of DNA, arguably the most conserved molecules in living organisms. However, AIM2 achieves specificity by detecting altered or mislocalized DNA molecules. It can detect damaged DNA, and the aberrant presence of DNA within the cytosolic compartment such as genomic DNA released into the cytosol upon loss of nuclear envelope integrity. AIM2 is also a key sensor of pathogens that detects the presence of foreign DNA accumulating in the cytosol during the life cycle of intracellular pathogens including viruses, bacteria, and parasites. AIM2 activation initiates the assembly of the inflammasome, an innate immune complex that leads to the activation of inflammatory caspases. This triggers the maturation and secretion of the cytokines IL‐1β and IL‐18. It can also initiate pyroptosis, a proinflammatory form of cell death. The AIM2 inflammasome contributes to physiological responses and diseases. It is a key player in host defenses, but its deregulation can contribute immune‐linked diseases, such as autoinflammatory and autoimmune pathologies. Moreover, AIM2 may play a role in cancer development. Recent studies have shown that the detection of self‐DNA species by AIM2 is an important factor that contributes to diseases associated with perturbation of cellular homeostasis. Thus, in addition of being a sensor of pathogen associated molecular patterns (PAMPs), the AIM2 inflammasome is emerging as a key guardian of cellular integrity.
Overview of the IL‐1 family in innate inflammation and acquired immunity
Authors: Dinarello Charles A. 
Published: December 2017

SummaryThe interleukin‐1 (IL‐1) family of cytokines and receptors is unique in immunology because the IL‐1 family and Toll‐like receptor (TLR) families share similar functions. More than any other cytokine family, the IL‐1 family is primarily associated with innate immunity. More than 95% of living organisms use innate immune mechanisms for survival whereas less than 5% depend on T‐ and B‐cell functions. Innate immunity is manifested by inflammation, which can function as a mechanism of host defense but when uncontrolled is detrimental to survival. Each member of the IL‐1 receptor and TLR family contains the cytoplasmic Toll‐IL‐1‐Receptor (TIR) domain. The 50 amino acid TIR domains are highly homologous with the Toll protein in Drosophila. The TIR domain is nearly the same and present in each TLR and each IL‐1 receptor family. Whereas IL‐1 family cytokine members trigger innate inflammation via IL‐1 family of receptors, TLRs trigger inflammation via bacteria, microbial products, viruses, nucleic acids, and damage‐associated molecular patterns (DAMPs). In fact, IL‐1 family member IL‐1a and IL‐33 also function as DAMPs. Although the inflammatory properties of the IL‐1 family dominate in innate immunity, IL‐1 family member can play a role in acquired immunity. This overview is a condensed update of the IL‐1 family of cytokines and receptors.
The New Third Generation: Post‐1965 Immigration and the Next Chapter in the Long Story of Assimilation
Authors: Jiménez Tomás R. , Park Julie , Pedroza Juan 
Published: December 2017

Now is the time for social scientists to focus an analytical lens on the new third generation to see what their experiences reveal about post‐1965 assimilation. This paper is a first step. We compare the household characteristics of post‐1965, second‐generation Latino and Asian children in 1980 to a “new third generation” in 2010. Today's new third generation is growing up in households headed by parents who have higher socioeconomic attainment; that are more likely to be headed by intermarried parents; that are less likely to contain extended family; and that, when living with intermarried parents, are more likely to have children identified with a Hispanic or Asian label compared to second‐generation children growing in 1980. We use these findings to inform a larger research agenda for studying the new third generation.
Sodium silicate activated slag‐fly ash binders: Part I – Processing, microstructure, and mechanical properties
Authors: Sankar Kaushik , Stynoski Peter , Al‐Chaar Ghassan K. , Kriven Waltraud M. 
Published: December 2017

AbstractAlkali silicate activated slag and class F fly ash‐based binders are ambient curing, structural materials that are feasible replacements for ordinary Portland cement (OPC). They exhibit advantageous mechanical properties and less environmental impact than OPC. In this work, five sodium silicate activated slag‐fly ash binder mixtures were developed and their compressive and flexural strengths were studied as a function of curing temperature and time. It was found that the strongest mixture sets at ambient temperature and had a Weibull average flexural strength of 5.7 ± 1.5 MPa and Weibull average compressive strength of 60 ± 8 MPa at 28 days. While increasing the slag/fly ash ratio accelerated the strength development, the cure time was decreased due to the formation of calcium silicate hydrate (C–S–H), calcium aluminum silicate hydrate (C–A–S–H), and (Ca,Na) based geopolymer. The density, microstructure, and phase evolution of ambient‐cured, heat‐cured, and heat‐treated binders were studied using pycnometry, scanning electron microscopy, energy dispersive X‐ray spectroscopy (SEM‐EDS), and X‐ray diffraction (XRD). Heat‐cured binders were more dense than ambient‐cured binder. No new crystalline phases evolved through 28 days in ambient‐ or heat‐cured binders.
Racial Disparities in Hospice Outcomes: A Race or Hospice‐Level Effect?
Authors: Rizzuto Jessica , Aldridge Melissa D. 
Published: December 2017

ObjectivesTo determine whether there is racial variation in hospice enrollees in rates of hospitalization and hospice disenrollment and, if so, whether systematic differences in hospice provider patterns explain the variation.DesignLongitudinal cohort study.SettingHospice.ParticipantsMedicare beneficiaries (N = 145,038) enrolled in a national random sample of hospices (N = 577) from the National Hospice Survey and followed until death (2009–10).MeasurementsWe used Medicare claims data to identify hospital admissions, emergency department (ED) visits, and hospice disenrollment after hospice enrollment. We used a series of hierarchical models including hospice‐level random effects to compare outcomes of blacks and whites.ResultsIn unadjusted models, black hospice enrollees were significantly more likely than white enrollees to be admitted to the hospital (14.9% vs 8.7%, odds ratio (OR) = 1.84, 95% confidence interval (CI) = 1.74–1.95), visit the ED (19.8% vs 13.5%, OR = 1.58, 95% CI = 1.50–1.66), and disenroll from hospice (18.1% vs 13.0%, OR = 1.48, 95% CI = 1.40–1.56). These results were largely unchanged after accounting for participant clinical and demographic covariates and hospice‐level random effects. In adjusted models, blacks were at higher risk of hospital admission (OR = 1.75, 95% CI = 1.64–1.86), ED visits (OR = 1.61, 95% CI = 1.52–1.70), and hospice disenrollment (OR = 1.54, 95% CI = 1.45–1.63).ConclusionRacial differences in intensity of care at the end of life are not attributable to hospice‐level variation in intensity of care. Differences in patterns of care between black and white hospice enrollees persist within the same hospice.
A novel wheat NAC transcription factor, TaNAC30, negatively regulates resistance of wheat to stripe rust
Authors: Wang Bing , Wei Jinping , Song Na , Wang Ning , Zhao Jing , Kang Zhensheng 
Published: December 2017

AbstractNAC transcription factors are widespread in the plant kingdom and play essential roles in the transcriptional regulation of defense responses. In this study, we isolated a novel NAC transcription factor gene, TaNAC30, from a cDNA library constructed from wheat (Triticum aestivum) plants inoculated with the stripe rust pathogen Puccinia striiformis f. sp. tritici (Pst). TaNAC30 contains a typical NAM domain and localizes to the nucleus. Yeast one‐hybrid assays revealed that TaNAC30 exhibits transcriptional activity and that its C‐terminus is necessary for the activation of transcription. Expression of TaNAC30 increased when host plants were infected with a virulent race (CYR31) of the rust fungus Pst. Silencing of TaNAC30 by virus‐induced gene silencing inhibited colonization of the virulent Pst isolate CYR31. Moreover, detailed histological analyses showed that silencing of TaNAC30 enhanced resistance to Pst by inducing a significant increase in the accumulation of H2O2. Finally, we overexpressed TaNAC30 in fission yeast and determined that cell viability was severely reduced in TaNAC30‐transformed cells grown on medium containing H2O2. These results suggest that TaNAC30 negatively regulates plant resistance in a compatible wheat‐Pst interaction.
Comparison of drug eluting balloon angioplasty to infrapopliteal artery critical lesions with or without additional pedal artery angioplasty in patients with diabetes mellitus and critical limb ischemia
Authors: Teymen Burak , Aktürk Süleyman 
Published: December 2017

BackgroundThe purpose of this study is to investigate the feasibility and outcome of balloon angioplasty for the treatment of below the ankle (BTA) lesions in addition to below the knee (BTK) lesions in diabetic patients with critical limb ischemia (CLI).MethodsInclusion criteria are diabetes mellitus (DM), CLI (Rutherford class 4 or higher) and revascularized significant stenosis or occlusion of at least 1 below‐the‐knee vessel with incomplete or no pedal loop. Target BTK vessel restenosis and reocclusion at 1‐year follow‐up was the primary end point whereas minor or major amputation at 1‐year follow‐up was the secondary end point.ResultsFrom July 2012 to June 2016, 48 diabetic patients identified with BTK with additionally BTA lesions were identified. Three patients were lost to follow‐up, leaving 45 patients. In 20 patients both BTK and BTA lesion (BTA group) was revascularized whereas only BTK lesion was treated in 25 patients (BTK group). The primary end point is 15.8% in BTA group and 47.8% in BTK group (p:0.059; P > 0.05). Minor or major amputation rate at 1‐year follow‐up was 15.8% in BTA group and 34.8% in BTA group (p:0.190; P > 0.05).ConclusionOur study shows that additional BTA angioplasty to BTK intervention may improve the primary patency rate and have higher event free rate, which slightly missed the margin of statistically significance. RBC decreased significantly more in BTA group compared to BTK group, which reflected that the outcome of intervention is better with additional BTA angioplasty.
Do Low‐Price Guarantees Guarantee Low Prices? Evidence from Competition between Amazon and Big‐Box Stores
Authors: Zhuo Ran 
Published: December 2017

AbstractIt has long been understood in theory that price‐match guarantees can be anticompetitive, but to date, scant empirical evidence is available outside of some narrow markets. This paper broadens the scope of empirical analysis, studying a wide range of products sold on a national online market. Using an algorithm that extracts data from charts, I obtain a novel source of data from online price trackers. I examine prices of goods sold on Amazon before and after two big‐box stores (Target and Best Buy) announced a guarantee to match Amazon's prices. Employing both difference‐in‐difference and regression‐discontinuity approaches, I robustly estimate a positive causal effect of six percentage points. The effect was heterogeneous, with larger price increases for initially lower‐priced items. My results support anticompetitive theories which predict price increases for Amazon, a firm that did not adopt the guarantee, and are consistent with plausible mechanisms for the heterogeneous impact.
Asymmetric Price Effects of Competition
Authors: Lach Saul , Moraga‐González José L. 
Published: December 2017

AbstractWhen price dispersion is prevalent, a relevant question is what happens to the whole distribution of equilibrium prices when the number of firms changes. Using data from the gasoline market in the Netherlands, we find, first, that markets with N competitors have price distributions that first‐order stochastically dominate the price distributions in markets with N+1 firms. Second, the effect of competition is stronger for the medium to upper percentiles of the price distribution. Finally, consumer gains from competition are larger for relatively well‐informed consumers. To account for these empirical patterns, we extend Varian's [1980] model by allowing for richer heterogeneity in consumer price information.
Sufficient Decisions in Multi‐Sided and Multiproduct Markets
Authors: Alexandrov Alexei , Spulber Daniel F. 
Published: December 2017

AbstractWe show that in many models where firms make multiple decisions, analysis can be made more tractable by re‐formulating the model into one in which each firm makes a single choice, which we call a sufficient decision. The transformation allows application of standard techniques in these settings, including pass‐through for tax incidence and upward pricing pressure for merger analysis. The transformation works because the assumption of profit maximization links the firms’ decisions together. Examples include models of monopoly and oligopoly in two‐sided markets, where a natural sufficient decision may be the number of transactions that the firm facilitates, and multiproduct markets.
Cognitive Abilities and Mathematical Competencies at School Entry
Authors: Ribner Andrew , Moeller Korbinian , Willoughby Michael , Blair Clancy ,   the Family Life Project Key Investigators
Published: December 2017

ABSTRACTThe aim of this study was to identify mathematical competencies in early childhood and cognitive correlates of those competencies in a prospective longitudinal sample of children (N = 1,292) in predominantly low‐income and nonurban communities in the United States. General mental ability, processing speed, vocabulary, and the working memory (WM), inhibitory control (IC), and cognitive flexibility components of executive function (EF) were assessed when children were aged 4 and 5 years. Math ability was assessed prior to school entry using a norm‐referenced assessment. Exploratory factor analysis indicated that items from the math assessment loaded onto factors representing conceptual and procedural skill. General mental ability, processing speed, vocabulary, and a unitary EF composite all related to both conceptual and procedural skill. When EF components were examined separately, however, only the IC aspect of EF was related to conceptual skill and only the WM aspect of EF was related to procedural skill.
Establishment of Photoaging In Vitro by Repetitive UVA Irradiation: Induction of Characteristic Markers of Senescence and its Prevention by PAPLAL with Potent Catalase Activity
Authors: Yoshimoto Satoshi , Yoshida Moemi , Ando Hideya , Ichihashi Masamitsu 
Published: December 2017

AbstractTo understand a role of UVA radiation in photoaging of the skin, we established a model of photoaging cells using cultured human dermal fibroblasts. Repeated low‐dose UVA radiation for 10 consecutive days induced senescence in fibroblasts, characterized with (1) increased level of senescence‐associated β‐galactosidase, (2) flattened large cell shape, (3) accumulation of reactive oxygen species, (4) yellowish coloration and (5) expression of p16. These were also observed in chronologically aged fibroblasts (doubling times >20), whereas none of these were detected in young cells (doubling times <10). Collectively, we propose that fibroblasts exposed to repetitive UVA radiation may be a good model of aged cells to study the mechanism of aging and photoaging and further to search for novel agents preventing cellular senescence. In addition, H2O2 was produced in the culture medium by a single low dose of UVA irradiation. Further, PAPLAL, a nanoparticle of platinum and palladium having potent catalase‐like activity, significantly delayed the onset of H2O2‐induced cell senescence. The present study strongly indicates that repetitive short‐term UVA irradiation induces aging of cells possibly via H2O2 and may be suppressed by potent anti‐H2O2 agents.
Measuring Environmental and Economic Opinions about Hydraulic Fracturing: A Survey of Landowners in Active or Planned Drilling Units
Authors: Arnold Gwen , Farrer Benjamin , Holahan Robert 
Published: December 2017

AbstractWe investigate how Eastern Ohio landowners affected by the recent boom in high‐volume hydraulic fracturing (HVHF) view the industry and the factors that affect their attitudes. Our unique sample almost exclusively contains individuals whose land is under lease for and/or experiencing HVHF. Nation‐ and state‐wide surveys that investigate HVHF attitudes tend to find nearly even splits between opposed and supportive respondents, whose views are strongly influenced by political partisanship. These trends largely do not manifest among Eastern Ohio landowners, for whom personal experiences with HVHF crucially influence attitudes. Most respondents support HVHF and say it has benefited their community economically. Political partisanship does not significantly impact HVHF views. Contrary to arguments in the literature that economic considerations drive variation in support for HVHF, landowners’ support for the industry also appears influenced by perceptions of its environmental and infrastructure impacts. Environmental concerns appear to more powerfully shape attitudes than economic benefits.