The intestinal epithelium forms a key protective barrier that separates internal organs from the harmful environment of the gut lumen. Increased permeability of the gut barrier is a common ...manifestation of different inflammatory disorders contributing to the severity of disease. Barrier permeability is controlled by epithelial adherens junctions and tight junctions. Junctional assembly and integrity depend on fundamental homeostatic processes such as cell differentiation, rearrangements of the cytoskeleton, and vesicle trafficking. Alterations of intestinal epithelial homeostasis during mucosal inflammation may impair structure and remodeling of apical junctions, resulting in increased permeability of the gut barrier. In this review, we summarize recent advances in our understanding of how altered epithelial homeostasis affects the structure and function of adherens junctions and tight junctions in the inflamed gut. Specifically, we focus on the transcription reprogramming of the cell, alterations in the actin cytoskeleton, and junctional endocytosis and exocytosis. We pay special attention to knockout mouse model studies and discuss the relevance of these mechanisms to human gastrointestinal disorders.
•Increased permeability of the gut barrier contributes to the development of inflammatory and immune disorders•Disruption of the gut barrier is mediated by disassembly of epithelial adherens and tight junctions•Increased endocytosis and attenuated exocytosis of junctional proteins mediate epithelial barrier breakdown•Actin filament turnover and myosin II activity regulate integrity and functions of intestinal epithelial junctions
Antibodies to DNA and chromatin drive autoimmunity in systemic lupus erythematosus (SLE). Null mutations and hypomorphic variants of the secreted deoxyribonuclease DNASE1L3 are linked to familial and ...sporadic SLE, respectively. We report that DNASE1L3-deficient mice rapidly develop autoantibodies to DNA and chromatin, followed by an SLE-like disease. Circulating DNASE1L3 is produced by dendritic cells and macrophages, and its levels inversely correlate with anti-DNA antibody response. DNASE1L3 is uniquely capable of digesting chromatin in microparticles released from apoptotic cells. Accordingly, DNASE1L3-deficient mice and human patients have elevated DNA levels in plasma, particularly in circulating microparticles. Murine and human autoantibody clones and serum antibodies from human SLE patients bind to DNASE1L3-sensitive chromatin on the surface of microparticles. Thus, extracellular microparticle-associated chromatin is a potential self-antigen normally digested by circulating DNASE1L3. The loss of this tolerance mechanism can contribute to SLE, and its restoration may represent a therapeutic opportunity in the disease.
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•Rapid anti-DNA antibody response, followed by SLE in Dnase1l3-deficient mice•Autoreactivity is repressed by circulating DNASE1L3 and is independent of STING•DNASE1L3 digests genomic DNA in microparticles released from apoptotic cells•DNASE1L3 prevents autoantibody binding to chromatin on microparticle surface
Extracellular microparticle-associated chromatin is a potential self-antigen normally digested by circulating DNASE1L3. The loss of this tolerance mechanism in mice and humans contributes to lupus, and the restoration of this mechanism may represent a therapeutic opportunity in the disease.
We report a study of the entanglement between the quantized photon field and an atom arising in the photo-ionization process. Our approach is based on an ab initio solution of the time-dependent ...Schrödinger equation (TDSE) describing the quantum evolution of a bipartite system consisting of the atom and the quantized electromagnetic field. Using the solution of the TDSE, we calculate the reduced photon density matrix, which we subsequently use to compute entanglement entropy. We explain some properties of the entanglement entropy and propose an approximate formula for the entanglement entropy based on the analysis of the density matrix and its eigenvalues. We present the results of a comparative study of the entanglement in the photo-ionization process for various ionization regimes, including the tunneling and the multiphoton ionization regimes.
Commensal bacteria are necessary for the development and maintenance of a healthy immune system. Harnessing the ability of microbiota to affect host immunity is considered an important therapeutic ...strategy for many mucosal and nonmucosal immune-related conditions, such as inflammatory bowel diseases (IBDs), celiac disease, metabolic syndrome, diabetes, and microbial infections. In addition to well-established immunostimulatory effects of the microbiota, the presence of individual mutualistic commensal bacteria with immunomodulatory effects has been described. These organisms are permanent members of the commensal microbiota and affect host immune homeostasis in specific ways. Identification of individual examples of such immunomodulatory commensals and understanding their mechanisms of interaction with the host will be invaluable in designing therapeutic strategies to reverse intestinal dysbiosis and recover immunological homeostasis.
Abstract
We describe an approach to the description of the time-development of the process of strong field ionization of atoms based on the calculation of the joint probability of occurrence of two ...events, event B being finding atom in the ionized state after the end of the laser pulse, event A being finding a particular value of a given physical observable at a moment of time inside the laser pulse duration. As an example of such an physical observable we consider lateral velocity component of the electron’s velocity. Our approach allows us to study time-evolution of the lateral velocity distribution for the ionized electron during the interval of the laser pulse duration. We present results of such a study for the cases of target atomic systems with short range Yukawa and Coulomb interactions.
Intestinal Th17 cells are induced and accumulate in response to colonization with a subgroup of intestinal microbes such as segmented filamentous bacteria (SFB) and certain extracellular pathogens. ...Here, we show that adhesion of microbes to intestinal epithelial cells (ECs) is a critical cue for Th17 induction. Upon monocolonization of germ-free mice or rats with SFB indigenous to mice (M-SFB) or rats (R-SFB), M-SFB and R-SFB showed host-specific adhesion to small intestinal ECs, accompanied by host-specific induction of Th17 cells. Citrobacter rodentium and Escherichia coli O157 triggered similar Th17 responses, whereas adhesion-defective mutants of these microbes failed to do so. Moreover, a mixture of 20 bacterial strains, which were selected and isolated from fecal samples of a patient with ulcerative colitis on the basis of their ability to cause a robust induction of Th17 cells in the mouse colon, also exhibited EC-adhesive characteristics.
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•A strong correlation between epithelial adhesion and Th17 induction by SFB and EHEC•Twenty Th17-inducing strains isolated from human feces show epithelial-adhesive property•Bacterial adhesion elicits a Th17-inducing gene-expression program in epithelium
The adhesion of specific members of the gut microbiome to intestinal epithelial cells is found to be essential for the induction of Th17 cells, thus highlighting location as an additional layer of regulation for the adaptive immune system.
How intestinal microbes regulate metabolic syndrome is incompletely understood. We show that intestinal microbiota protects against development of obesity, metabolic syndrome, and pre-diabetic ...phenotypes by inducing commensal-specific Th17 cells. High-fat, high-sugar diet promoted metabolic disease by depleting Th17-inducing microbes, and recovery of commensal Th17 cells restored protection. Microbiota-induced Th17 cells afforded protection by regulating lipid absorption across intestinal epithelium in an IL-17-dependent manner. Diet-induced loss of protective Th17 cells was mediated by the presence of sugar. Eliminating sugar from high-fat diets protected mice from obesity and metabolic syndrome in a manner dependent on commensal-specific Th17 cells. Sugar and ILC3 promoted outgrowth of Faecalibaculum rodentium that displaced Th17-inducing microbiota. These results define dietary and microbiota factors posing risk for metabolic syndrome. They also define a microbiota-dependent mechanism for immuno-pathogenicity of dietary sugar and highlight an elaborate interaction between diet, microbiota, and intestinal immunity in regulation of metabolic disorders.
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•Commensal-induced Th17 cells regulate epithelial lipid absorption•Sugar and ILC3 increase Faecalibaculum rodentium to displace Th17-inducing bacteria•Microbiota-induced Th17 cells protect from diet-induced obesity and metabolic disease•Sugar eliminates commensal Th17 cells to increase the risk for metabolic disease
Sugar in mouse diets promotes metabolic disease by upsetting the gut microbial balance and driving loss of the Th17 cells that regulate lipid absorption by the intestinal epithelium.
Symmetry breaking patterns in 3HDM Ivanov, I. P.; Nishi, C. C.
The journal of high energy physics,
01/2015, Letnik:
2015, Številka:
1
Journal Article, Web Resource
Recenzirano
Odprti dostop
A
bstract
An attractive feature of New Physics models with multiple Higgs fields is that they are equipped with discrete symmetry groups in the Higgs and flavour sectors. These symmetry groups are ...often broken at the global minimum of the Higgs potential, either completely or to a proper subgroup, with certain phenomenological consequences. Here, we systematically explore these symmetry breaking patterns in the scalar sector of the three-Higgs-doublet model (3HDM). We use the full list of discrete symmetry groups allowed in 3HDM, and for each group we find all possible ways it can break by the Higgs vacuum expectation value alignment. We also discuss the interplay between these symmetry groups and various forms of
CP
-violation in the scalar sector of 3HDM. Not only do our results solve the problem for 3HDM, but they also hint at several general features in multi-scalar sectors.
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