325 research outputs found
The role of the macrophage in sentinel responses in intestinal immunity
Get PDFThe purpose of this review is to highlight macrophages as central mediators of intestinal immune homeostasis and inflammation
<html>Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4<sup>+</sup>CD45RB<sup>high</sup> T Cells into Immunodeficient Mice</html>
Get PDFThere are many different animal models available for studying the pathogenesis of human inflammatory bowel diseases (IBD), each with its own advantages and disadvantages. We describe here an experimental colitis model that is initiated by adoptive transfer of syngeneic splenic CD4+CD45RBhigh T cells into T and B cell deficient recipient mice. The CD4+CD45RBhigh T cell population that largely consists of naïve effector cells is capable of inducing chronic intestinal inflammation, closely resembling key aspects of human IBD. This method can be manipulated to study aspects of disease onset and progression. Additionally it can be used to study the function of innate, adaptive, and regulatory immune cell populations, and the role of environmental exposures, i.e., the microbiota, in intestinal inflammation. In this article we illustrate the methodology for inducing colitis with a step-by-step protocol. This includes a video demonstration of key technical aspects required to successfully develop this murine model of experimental colitis for research purposes
Ceramic-reinforced HEA matrix composites exhibiting an excellent combination of mechanical properties
Get PDFCoCrFeNi is a well-studied face centered cubic (fcc) high entropy alloy (HEA) that exhibits excellent
ductility but only limited strength. The present study focusses on improving the strength-ductility
balance of this HEA by addition of varying amounts of SiC using an arc melting route. Chromium
present in the base HEA is found to result in decomposition of SiC during melting. Consequently,
interaction of free carbon with chromium results in the in-situ formation of chromium carbide, while
free silicon remains in solution in the base HEA and/or interacts with the constituent elements of the
base HEA to form silicides. The changes in microstructural phases with increasing amount of SiC are
found to follow the sequence: fcc → fcc + eutectic → fcc + chromium carbide platelets → fcc + chromium
carbide platelets + silicides → fcc + chromium carbide platelets + silicides + graphite globules/flakes.
In comparison to both conventional and high entropy alloys, the resulting composites were found to
exhibit a very wide range of mechanical properties (yield strength from 277 MPa with more than 60%
elongation to 2522 MPa with 6% elongation). Some of the developed high entropy composites showed
an outstanding combination of mechanical properties (yield strength 1200 MPa with 37% elongation)
and occupied previously unattainable regions in a yield strength versus elongation map. In addition
to their significant elongation, the hardness and yield strength of the HEA composites are found to
lie in the same range as those of bulk metallic glasses. It is therefore believed that development of
high entropy composites can help in obtaining outstanding combinations of mechanical properties for
advanced structural applications.Financial support from the Higher Education Commission of Pakistan (HEC NRPU 6019) is acknowledged. FEDER National funds FCT under the project CEMMPRE, ref. “UIDB/00285/2020” is also acknowledged.info:eu-repo/semantics/publishedVersio
Capital Structure Dynamics of Shariah-Compliant vs Non-Compliant Firms: Evidence from Pakistan
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This study aims to compare capital structure determinants' effect on the leverage levels of Shariah-compliant (SC) and noncompliant (NC) firms in Pakistan. This study also estimates and compares the capital structure adjustment speed for both firm types.
Design/methodology/approach
Based on the Karachi Meezan Index screening criterion, a balanced panel of 117 SC and 68 NC firms listed on the Pakistan Stock Exchange from 2008 to 2018 was constituted. This study used the generalized method of moments to identify the significant determinants of capital structure and estimate the speed of adjustment. In addition, the F-test was used to check whether the effect of the determinants on the leverage is same for SC and non-SC firms.
Findings
The authors found that different determinants affect both firm types' leverage levels (book and market) differently. The authors also found that the adjustment speed of SC firms toward their target leverage ratio is slower than their NC peers. Lastly, significant variation was observed in the results under different screening criteria.
Research limitations/implications
This study fills the literature gap by providing a comprehensive comparison of the capital structure decisions of the SC and non-SC firms. Because this study is limited to Pakistan, generalizability would be an issue.
Practical implications
This study will guide the management of SC and non-SC firms about which factors are reliably important in choosing their capital structure. The findings also call for bringing harmony in the different Shariah screening criteria being in practice.
Originality/value
To the best of the authors’ knowledge, this is the first comparative study that identifies the significant capital structure determinants for SC and NC firms and investigates their effect on the leverage of both firm types. By testing joint hypotheses of same relationship, this study seeks to determine if, because of Shariah restrictions, the capital structure determinants of SC firms are similar to NC firms or they exhibit different behavior. The authors also repeat their analysis using other prominent screening criteria to assess the consistency of their results
Cutting Edge: IFN- Is a Negative Regulator of IL-23 in Murine Macrophages and Experimental Colitis
Get PDFIL-23 regulation is a central event in the pathogenesis of the inflammatory bowel diseases. We demonstrate that IFN-γ has anti-inflammatory properties in the initiation phase of IL-23–mediated experimental colitis. IFN-γ attenuates LPS-mediated IL-23 expression in murine macrophages. Mechanistically, IFN-γ inhibits Il23a promoter activation through altering NF-κB binding and histone modification. Moreover, intestinal inflammation is inhibited by IFN-γ signaling through attenuation of Il23a gene expression. In germ-free wild-type mice colonized with enteric microbiota, inhibition of colonic Il23a temporally correlates with induction of IFN-γ. IFN-γR1/IL-10 double-deficient mice demonstrate markedly increased colonic inflammation and IL23a expression compared with those of IL-10−/− mice. Colonic CD11b+ cells are the primary source of IL-23 and a target for IFN-γ. This study describes an important anti-inflammatory role for IFN-γ through inhibition of IL-23. Converging genetic and functional findings suggest that IL-23 and IFN-γ are important pathogenic molecules in human inflammatory bowel disease
Avoiding catastrophic failure in correlated networks of networks
Get PDFNetworks in nature do not act in isolation but instead exchange information,
and depend on each other to function properly. An incipient theory of Networks
of Networks have shown that connected random networks may very easily result in
abrupt failures. This theoretical finding bares an intrinsic paradox: If
natural systems organize in interconnected networks, how can they be so stable?
Here we provide a solution to this conundrum, showing that the stability of a
system of networks relies on the relation between the internal structure of a
network and its pattern of connections to other networks. Specifically, we
demonstrate that if network inter-connections are provided by hubs of the
network and if there is a moderate degree of convergence of inter-network
connection the systems of network are stable and robust to failure. We test
this theoretical prediction in two independent experiments of functional brain
networks (in task- and resting states) which show that brain networks are
connected with a topology that maximizes stability according to the theory.Comment: 40 pages, 7 figure
Flexible Dielectric Nanocomposites with Ultrawide Zero-Temperature Coefficient Windows for Electrical Energy Storage and Conversion under Extreme Conditions
Get PDFPolymer dielectrics offer key advantages over their ceramic counterparts such as flexibility, scalability, low cost, and high breakdown voltages. However, a major drawback that limits more widespread application of polymer dielectrics is their temperature-dependent dielectric properties. Achieving dielectric constants with low/zero-temperature coefficient (L/0TC) over a broad temperature range is essential for applications in diverse technologies. Here, we report a hybrid filler strategy to produce polymer composites with an ultrawide L/0TC window of dielectric constant, as well as a significantly enhanced dielectric value, maximum energy storage density, thermal conductivity, and stability. By creating a series of percolative polymer composites, we demonstrated hybrid carbon filler based composites can exhibit a zero-temperature coefficient window of 200 °C (from -50 to 150 °C), the widest 0TC window for all polymer composite dielectrics reported to date. We further show the electric and dielectric temperature coefficient of the composites is highly stable against stretching and bending, even under AC electric field with frequency up to 1 MHz. We envision that our method will push the functional limits of polymer dielectrics for flexible electronics in extreme conditions such as in hybrid vehicles, aerospace, power electronics, and oil/gas exploration.This work is supported by National Science Foundation of China (Grant Nos. 61006077, 61274123, 61425201, and 61474099), ZJ-NSF (LR12F04001). Y. Xu is supported by ZJU Cyber Scholarship and Cyrus Tang Center for Sensor Materials and Applications, and Visiting-by-Fellowship of Churchill College, University of Cambridge. T. Hasan is supported by The Royal Academy of Engineering (Graphlex)
Aberrant miR-29 is a predictive feature of severe phenotypes in pediatric Crohn’s disease
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Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice
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Poncirin is flavanone derivative (isolated from Poncirus trifoliata) with known pharmacological activities such as anti-tumor, anti-osteoporotic, anti-inflammatory and anti-colitic. The present study aimed to explore the anti-allodynic and anti-hyperalgesic potentials of poncirin in murine models of inflammatory pain.
Methods
The analgesic potential of poncirin was evaluated in formalin-, acetic acid-, carrageenan- and Complete Freunds Adjuvant (CFA)-induced inflammatory pain models in mice. Anti-allodynic and anti-hyperalgesic activities were measured using Von Frey filaments, Randall Selitto, hotplate and cold acetone tests. The serum nitrite levels were determined using Griess reagent. The Quantitative Real-time PCR (qRT-PCR) was performed to assess the effect of poncirin on mRNA expression levels of inflammatory cytokines and anti-oxidant enzymes.
Results
Intraperitoneal administration of poncirin (30 mg/kg) markedly reduced the pain behavior in both acetic acid-induced visceral pain and formalin-induced tonic pain models used as preliminary screening tools. The poncirin (30 mg/kg) treatment considerably inhibited the mechanical hyperalgesia and allodynia as well as thermal hyperalgesia and cold allodynia. The qRT-PCR analysis showed noticeable inhibition of pro-inflammatory cytokines (mRNA expression levels of TNF-α, IL-1β and IL-6) (p < 0.05) in poncirin treated group. Similarly, poncirin treatment also enhanced the mRNA expressions levels of anti-oxidant enzymes such as transcription factor such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2) (p < 0.05), heme oxygenase (HO-1) (p < 0.05) and superoxide dismutase (SOD2) (p < 0.05). Chronic treatment of poncirin for 6 days did not confer any significant hepatic and renal toxicity. Furthermore, poncirin treatment did not altered the motor coordination and muscle strength in CFA-induced chronic inflammatory pain model.
Conclusion
The present study demonstrated that poncirin treatment significantly reduced pain behaviors in all experimental models of inflammatory pain, suggesting the promising analgesic potential of poncirin in inflammatory pain conditions.The Higher Education Commission (HEC) of Pakistan (under the SRGP funding No. 357SRGP/HEC/2014) supported the study only financially and was not involved in the designing of the project. The authors are grateful to the National Research Foundation of Korea (NRF), Seoul National University, grant funded by the Korean Government (MSIP) (No. 2009–0083533). The Proff: Yeong Shik Kim (National Research Foundation of Korea (NRF), Seoul National University) was actively involved in the designing of the experiment and analysis of the results
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