Ichthyotic disorders
Biju Vasudevan, Rajesh Verma in Dermatological Emergencies, 2019
Conradi-Hünermann-Happle (CHH) syndrome is a rare X-linked dominant multisystem disorder. It occurs due to postzygotic mutation in the EBP (emopamil binding protein) gene on chromosome Xp11.23. It is characterized by linear ichthyosis, chondrodysplasia punctata, cataract, and short stature. The child is born with severe ichthyosiform erythroderma, and the scales are arranged in swirls and whorls along the lines of Blaschko. With age, ichthyosis improves and mild ichthyosis presents on the extremities along with follicular atrophoderma along the lines of Blaschko with hypopigmented and hyperpigmented streaks on the trunk. There may be persistent psoriasiform lesions in intertriginous areas (ptychotrophism) [15]. Localized scarring alopecia may be seen. Other features include asymmetrical skeletal involvement with stippled calcification of the epiphyseal region resulting in shortening of long bones, severe kyphoscoliosis, congenital dislocation of the hip, facial dysplasia, congenital heart defects, sensorineural deafness, renal anomalies, and ophthalmological changes like cataract, microphthalmia, and microcornea.
Staphylococcus
Dongyou Liu in Handbook of Foodborne Diseases, 2018
Various proteins (e.g., membrane proteins, membrane–cell wall interface proteins, cell wall–associated proteins, and other secretory proteins) determine the bacterial pathogenicity. These proteins also play a crucial role in host immune evasion, colonization and invasion of host tissue, and direct cytotoxicity against host [2]. The extracellular and cell wall–associated proteins of S. aureus are known as secretome and surfacome, respectively, and are important virulence factors for host colonization and subsequent acute infection [2]. Some of the surface proteins function as adhesins. For example, staphylococcal protein A (Spa) can bind to the Fc portion of immunoglobulin and exhibit its antiphagocytic properties [4]. Elastin-binding protein (Ebp) and serine-aspartate repeat proteins (Sdrs—SdrC, SdrD, SdrE) also act as adhesins. The process of S. aureus colonization involves binding of fibrinogen, fibronectin, and cytokeratins most commonly within human nasal epithelium or epidermis mediated by surface-exposed proteins known as MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) that include fibronectin-binding proteins A and B (FnBPA and FnBPB), collagen-binding protein (Can), Spa, and iron-regulated determinants (Isd—IsdA, IsdB, IsdC, IsdH) that promote bacterial adhesion to squamous cells and prevent cytotoxic killings. S. aureus adhesion to squamous cell is promoted by staphylococcal surface protein such as SasG. Other proteins such as von Willebrand factor-binding protein (vWbp) coagulase (Coa) facilitate colonization via activation of prothrombin. The localized clot formation from this process contains the bacteria in a pseudocapsule, thus preventing it from host immune defense. After successful colonization within host tissue, the virulence factors containing enzymes and nonenzymatic toxins such as hemolysins, leukocidins, and Panton-Valentine leukocidin (PVL), mediate detachment and spread within the host. These enzymes provide nutrient and defense against host immune responses [2].
Eosinophil Membrane Receptors: Function of IgE- and IgA-Binding Molecules
Gerald J. Gleich, A. Barry Kay in Eosinophils in Allergy and Inflammation, 2019
The involvement of Mac-2/eBP in the IgE-dependent functions of eosinophils was also investigated, since Mac-2/eBP has been shown to bind IgE through its carbohydrate moiety (13). Experiments of inhibition of radiolabeled IgE binding were performed to study whether Mac-2/eBP could be involved in IgE binding to eosinophils (Table 1). Anti-Mac-2 monoclonal antibody (MAb) significantly inhibited, in a dose-dependent manner, the binding of 125I IgE, in contrast to control MAb. Moreover, in order to evaluate whether the molecules recognized by anti-Mac-2 MAb could participate in the IgE-dependent effector function of eosinophils, the effect of anti-Mac-2 MAb was investigated in a cytotoxicity assay involving eosinophils and polyclonal IgE antibodies from patients (Table 1). Anti-Mac-2 MAb strongly inhibited IgE-dependent cytotoxicity of hypodense eosinophils against schistosome larvae, by comparison with control antibodies. These results indicate the participation of Mac-2/eBP in IgE binding and IgE-dependent cytotoxicity mediated by eosinophils. FceRII/CD23, which presents significant sequence homology with a class of animal lectins (17), has been shown to be also involved in these functions (7). However, in the case of C-type (calcium-dependent-binding) lectins, IgE binding to FceRII is pH-dependent but independent of the carbohydrate structure of IgE (18,19). In contrast to FceRII/CD23, Mac-2 and heBP bind to IgE in a carbohydrate-dependent manner and show heterogeneity in the binding of various IgE glycoforms (13,20). The participation of the two groups of IgE-binding molecules (CD23 and Mac-2/eBP) in the cytotoxic function of eosinophils suggest an important role in the recognition of IgE by CRD domains of C- and S-type lectins. In addition to the role of Mac-2/eBP in IgE binding to eosinophils, the inhibition by anti-Mac-2 MAb of eosinophil adhesion to parasite targets also suggests the function of such molecules as cell adhesion proteins and should be explored in other adhesive properties of eosinophils.
From a basic to a functional approach for developing a blood stage vaccine against Plasmodium vivax
Published in Expert Review of Vaccines, 2020
Manuel Alfonso Patarroyo, Gabriela Arévalo-Pinzón, Darwin A. Moreno-Pérez
In-depth knowledge of which fragments are essential in parasite–cell interaction must first be obtained before beginning studies in animal models. Functional restriction analysis has been shown to be useful for identifying essential regions for reticulocyte binding which the parasite protects by using highly antigenic but polymorphic regions as smoke screens. This must be followed by roughly identifying protein regions having binding activity through protein–cell interaction trials, as has been done with PvEBP, PvGAMA, PvRBSA, PvAMA1, PvRON2, and PvRON4. CD71+ reticulocyte enriched samples (UCB) and/or other sources (JK-1 cells or ejRBC) must be used for functionally characterizing the molecules mediating parasite–cell interaction and determining the significance of such protein interactions.
Targeting endoplasmic reticulum stress—the responder to lipotoxicity and modulator of non-alcoholic fatty liver diseases
Published in Expert Opinion on Therapeutic Targets, 2022
Yu Luo, Qiangqiang Jiao, Yuping Chen
UPR is controlled by transmembrane ER stress sensors: protein kinase R-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1α) and activating transcription factor 6 (ATF6α) [4,9]. They are unbound from ER luminal binding immunoglobulin protein (BiP) upon ER stress and/or direct contact to unfolded/misfolded protein, either getting activated via dimerization and auto-phosphorylation (like PERK and IRE1α) [1] or being cleaved by site‐1 protease (S1P) and site‐2 protease (S2P) in Golgi apparatus to form cleaved ATF6 (ATF6 p50) [5]. Phosphorylated PERK (p-PERK) phosphorylates eukaryotic initiation factor-2α (eIF2α) to suppress global protein translation, and phosphorylated eIF2α (p-eIF2α) also selectively increases the translation of a numbers of mRNAs such as activating transcription factor 4 (ATF4) and glutamine rich 1, upregulating the proteins necessary for ER-associated degradation (ERAD), protein folding, and antioxidant response, or increasing the CCAAT/enhancer-binding protein (C/EBP) homologues protein (CHOP) to mediate ER stress-induced apoptosis and proteotoxicity [4]. Phosphorylated IRE1α (p-IRE1α) activates c-Jun N-terminal kinase (JNK) pathways via its kinase activity [9]. It also exerts endoribonuclease activity to generate transcriptionally active spliced X-box binding protein 1 (sXBP1) to regulate the genes for chaperones, ERAD, and autophagy [1,10], or to inhibit gene expression through the regulated IRE1α-dependent decay (RIDD)-mediated mRNA decay [11]. Chaperones and ERAD are also under the transcriptional control by ATF6 p50[1].
Can trophectoderm RNA analysis predict human blastocyst competency?
Published in Systems Biology in Reproductive Medicine, 2019
Panagiotis Ntostis, Georgia Kokkali, David Iles, John Huntriss, Maria Tzetis, Helen Picton, Konstantinos Pantos, David Miller
The edgeR exact test was used to reveal significantly differentially expressed (DE) transcripts between competent and incompetent blastocysts (Figure 1; please see Μaterials and Μethods supplementary file for full details). The DE transcripts belonged to 47 unique genes (Table 1). Given that the competent group represents normal TE expression levels, the current study focused on the significantly lower/higher expression levels of the incompetent blastocysts. Following normalization of the RNA sequencing results, 36 transcripts were found to be significantly down-regulated in these blastocysts with the remainder being up-regulated (FDR < 0.05). These included KH Domain Containing 1 Pseudogene 1 (KHDC1P1), the apoptosis regulator BCL2 Antagonist/Killer 1 (BAK1), suggesting a potentially significant regulatory function perhaps relating to an underlying apoptotic process. All DE transcripts had at least three-fold-change, apart from KH RNA Binding Domain Containing, Signal Transduction Associated 3 (KHDRBS3) and Emopamil Binding Protein (Sterol Isomerase; EBP) that were slightly lower at 2.7-fold.
Related Knowledge Centers
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