79 research outputs found
Defining a T Cell-Intrinsic Role for MyD88 During LCMV infection
Immune activation through Toll-like receptors (TLRs) has historically been considered to be a characteristic of cells of the innate, rather than adaptive immune system. Recent studies have challenged this paradigm by demonstrating that TLRs are also expressed on T lymphocytes and that TLR ligands can directly co-stimulate T cell responses in vitro. However, the physiological relevance of these findings during in vivo immune responses was unclear. Mice lacking the critical TLR-adapter protein, myeloid differentiation protein 88 (MyD88), have increased susceptibility to numerous pathogens, highlighting the importance of TLRs in host defense. While the immune impairments associated with MyD88-deficiency have generally been attributed to the importance of MyD88 in regulating innate immune responses, in light of the studies showing that TLRs can directly stimulate T cells, we hypothesized that they may also reflect a direct role for MyD88 in T cells. In this work, we use lymphocytic choriomeningitis virus (LCMV) as a model infection to examine the role of MyD88 in regulating antiviral T cell responses. Using a series of adoptive cell transfer and bone marrow chimera experiments, we identify a critical, but previously unappreciated, T-cell intrinsic role for MyD88 in regulating the survival and expansion of LCMV-specific effector T cells during acute viral infection. Using a system to inducibly delete MyD88 we also show that, while naïve T cells critically depend on MyD88-dependent signals for their expansion, virus-specific memory T cells do not require MyD88 for their differentiation, maintenance or reactivation in response to secondary infection. Overall, our findings broaden the importance of MyD88 in T cells, support a shift in the dogma that restricts the role MyD88 to cells of the innate immune system, and may have significant implications for understanding the signals that control T cell survival during inflammatory immune responses
FE Analysis of Creep and Hygroexpansion Response of a Corrugated Fiberboarad to a Moisture Flow: a Transient Nonlinear Analysis
This paper presents a model using finite element method to study the response of a typical commercial corrugated fiberboard due to an induced moisture function at one side of the fiberboard. The model predicts how the moisture diffusion will permeate through the fiberboard's layers (medium and liners) providing information on moisture content at any given point throughout the structure. The hygroexpansion response and the creep response were predicted through the development of a finite element model capable of capturing the behavior of the fiberboard. Comparing the results generated from the model with actual experimental results validates the accuracy of the computational model. The model predicts the deformation response due to combined hygroexpansion and creep as the relative humidity rises from 38% RH to 86%. The parameters studied and calibrated include: the coefficient of moisture diffusion of the liner and the medium boards, the coefficient of moisture expansion, and the constants in the creep constitutive law. The results generated from the finite element model showed excellent agreement with the experimental results for a short column corrugated fiberboard and a board model representing a container box side-panel dimension. The results were generated in a cyclic relative humidity condition. A successful development of a reliable computational model holds the promise for analyzing collapse mechanism of container boxes in the service field under real weather condition data without dependency on expensive time-consuming experimental investigations. This is of great benefit to the shipping industry and the public
EGR-2 Is Not Required for In Vivo CD4 T Cell Mediated Immune Responses
Background: The zinc finger transcription factor EGR-2 has been shown to play an important role in the induction of T cell anergy and the regulation of peripheral T cell tolerance. In vitro, a prior study has show that T cells deficient in EGR-2 are hyperproliferative to IL-2 and produce elevated levels of the effector cytokine IFN-c. EGR-2 deficient mice have increased levels of CD44 high T cells in peripheral lymphoid organs, and with age, develop autoimmune-like features. Principal Findings: Here we show that despite increased numbers of cells bearing an activated CD44 high CD62L low phenotype, T cells from young healthy EGR-2 deficient mice have normal proliferative and cytokine responses, and the mice themselves mount normal immune responses against minor histocompatibility antigens, and the pathogens Toxoplasma gondii and lymphocytic choriomeningitis virus. Conclusions: Our results indicate that EGR-2 is not required to mount normal acute in vivo immune responses against foreign antigens, and suggest instead that it may serve to regulate the response to chronic antigenic exposure, such as tha
Induction of Systemic Resistance in Maize and Antibiofilm Activity of Surfactin From Bacillus velezensis MS20
Surfactin lipopeptide is an eco-friendly microbially synthesized bioproduct that holds considerable potential in therapeutics (antibiofilm) as well as in agriculture (antifungal). In the present study, production of surfactin by a marine strain Bacillus velezensis MS20 was carried out, followed by physico-chemical characterization, anti-biofilm activity, plant growth promotion, and quantitative Reverse Transcriptase-Polymerase Chain Reaction (q RT-PCR) studies. From the results, it was inferred that MS20 was found to produce biosurfactant (3,300 mg L-1) under optimized conditions. From the physicochemical characterization [Thin layer chromatography (TLC), Fourier Transform Infrared (FTIR) Spectroscopy, Liquid Chromatography/Mass Spectroscopy (LC/MS), and Polymerase Chain Reaction (PCR) amplification] it was revealed to be surfactin. From bio-assay and scanning electron microscope (SEM) images, it was observed that surfactin (MIC 50 mu g Ml(-1)) has appreciable bacterial aggregation against clinical pathogens Pseudomonas aeruginosa MTCC424, Escherichia coli MTCC43, Klebsiella pneumoniae MTCC9751, and Methicillin resistant Staphylococcus aureus (MRSA) and mycelial condensation property against a fungal phytopathogen Rhizoctonia solani. In addition, the q-RTPCR studies revealed 8-fold upregulation (9.34 +/- 0.11-fold) of srfA-A gene compared to controls. Further, treatment of maize crop (infected with R. solani) with surfactin and MS20 led to the production of defense enzymes. In conclusion, concentration and synergy of a carbon source with inorganic/mineral salts can ameliorate surfactin yield and, application wise, it has antibiofilm and antifungal activities. In addition, it induced systemic resistance in maize crop, which makes it a good candidate to be employed in sustainable agricultural practices.Peer reviewe
The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via modification of the signaling adaptor TRAF6 and transcription factor NF-κB
Several members of the NLR family of sensors activate innate immunity. In contrast, we found here that NLRC3 inhibited Toll-like receptor (TLR)-dependent activation of the transcription factor NF-κB by interacting with the TLR signaling adaptor TRAF6 to attenuate Lys63 (K63)-linked ubiquitination of TRAF6 and activation of NF-κB. We used bioinformatics to predict interactions between NLR and TRAF proteins, including interactions of TRAF with NLRC3. In vivo, macrophage expression of Nlrc3 mRNA was diminished by the administration of lipopolysaccharide (LPS) but was restored when cellular activation subsided. To assess biologic relevance, we generated Nlrc3−/− mice. LPS-treated Nlrc3−/− macrophages had more K63-ubiquitinated TRAF6, nuclear NF-κB and proinflammatory cytokines. Finally, LPS-treated Nlrc3−/− mice had more signs of inflammation. Thus, signaling via NLRC3 and TLR constitutes a negative feedback loop. Furthermore, prevalent NLR-TRAF interactions suggest the formation of a ‘TRAFasome’ complex
A Finite Element Investigation of the Role of Adhesive in the Buckling Failure of Corrugated Fiberboard
Considerable research has focused on the role of linerboard and medium components in the overall strength of fiberboard. However, limited research has been done on the role of the adhesive in the structural performance of corrugated fiberboard and the container box. This research study proposed to include the glue material in a finite element (FE) model that represents the actual geometry and material properties of corrugated fiberboard. The model is a detailed representation of the different components of the structure (adhesive, linerboard, medium) to perform buckling analysis of corrugated structures under compressive loads. The objective of this analysis was to quantify the influence of the adhesive on the structural performance of corrugated fiberboard. Adhesive parameters are identified in terms of material properties. The modulus of elasticity of the adhesive is taken relative to the modulus of a linerboard material. Three adhesive stiffness properties representing minimum, medium, and maximum moduli values are considered. The analysis also addresses the buckling failure of fiberboard when adhesion is ineffective along a glueline. Results show that increasing the adhesive modulus (20 times that of linerboard) tends to strengthen the fiberboard buckling carrying capacity up to 50%. Loss of adhesive along a fiberboard glueline also substantially decreases the buckling strength of the structure
When an Intruder Comes Home: GM and GE Strategies to Combat Virus Infection in Plants
Viruses are silent enemies that intrude and take control of the plant cell’s machinery for their own multiplication. Infection by viruses and the resulting damage is still a major challenge in the agriculture sector. Plants have the capability to fight back, but the ability of viruses to mutate at a fast rate helps them to evade the host’s response. Therefore, classical approaches for introgressing resistance genes by breeding have obtained limited success in counteracting the virus menace. Genetic modification (GM)-based strategies have been successful in engineering artificial resistance in plants. Several different approaches based on pathogen-derived resistance, antisense constructs, hairpin RNAs, double-stranded RNA, etc., have been used to enhance plants’ resistance to viruses. Recently, genome editing (GE) strategies mainly involving the CRISPR/Cas-mediated modifications are being used for virus control. In this review, we discuss the developments and advancements in GM- and GE-based methods for tackling viral infection in plants
A Non-Linear 3D FEM to Simulate Un-Bonded Steel Reinforcement Bars under Axial and Bending Loads
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