Classification, structural biology, and applications of mucin domain-targeting proteases

2021 ◽  
Vol 478 (8) ◽  
pp. 1585-1603
Author(s):  
D. Judy Shon ◽  
Angel Kuo ◽  
Michael J. Ferracane ◽  
Stacy A. Malaker

Epithelial surfaces throughout the body are coated by mucins, a class of proteins carrying domains characterized by a high density of O-glycosylated serine and threonine residues. The resulting mucosal layers form crucial host-microbe interfaces that prevent the translocation of microbes while also selecting for distinct bacteria via the presented glycan repertoire. The intricate interplay between mucus production and breakdown thus determines the composition of the microbiota maintained within these mucosal environments, which can have a large influence on the host during both homeostasis and disease. Most research to date on mucus breakdown has focused on glycosidases that trim glycan structures to release monosaccharides as a source of nutrients. More recent work has uncovered the existence of mucin-type O-glycosylation-dependent proteases that are secreted by pathogens, commensals, and mutualists to facilitate mucosal colonization and penetration. Additionally, immunoglobulin A (IgA) proteases promote bacterial colonization in the presence of neutralizing secretory IgA through selective cleavage of the heavily O-glycosylated hinge region. In this review, we summarize families of O-glycoproteases and IgA proteases, discuss known structural features, and review applications of these enzymes to glycobiology.

2020 ◽  
pp. 1-15
Author(s):  
Kenneth W. Yu

How to inculcate virtue in the citizens of Magnesia by means of the dance component of choreia constitutes one of the principal concerns in the Laws (= Leg.), revealing Plato's evolving ideas about the expediency of music and paideia for the construction of his ideal city since the Republic. Indeed, a steady stream of monographs and articles on the Laws has enriched our understanding of how Plato theorizes the body as a site of intervention and choral dance as instrumental in solidifying social relations and in conditioning the ethical and political self. As one scholar has aptly put it: ‘a city and its sociopolitical character [are] effectively danced into existence.’ Drawing on this recent work, I focus on an enigmatic passage in Laws Book 7 that merits more attention than it has received, in which Plato curiously singles out Bacchic dances from those that are ‘without controversy’ (815b7–d4): τὴν τοίνυν ἀμφισβητουμένην ὄρχησιν δεῖ πρῶτον χωρὶς τῆς ἀναμφισβητήτου διατεμεῖν. τίς οὖν αὕτη, καὶ πῇ δεῖ χωρὶς τέμνειν ἑκατέραν; ὅση μὲν βακχεία τ᾽ ἐστὶν καὶ τῶν ταύταις ἑπομένων, ἃς Νύμφας τε καὶ Πᾶνας καὶ Σειληνοὺς καὶ Σατύρους ἐπονομάζοντες, ὥς φασιν, μιμοῦνται κατῳνωμένους, περὶ καθαρμούς τε καὶ τελετάς τινας ἀποτελούντων, σύμπαν τοῦτο τῆς ὀρχήσεως τὸ γένος οὔθ᾽ ὡς εἰρηνικὸν οὔθ᾽ ὡς πολεμικὸν οὔθ᾽ ὅτι ποτὲ βούλεται ῥᾴδιον ἀφορίσασθαι: διορίσασθαι μήν μοι ταύτῃ δοκεῖ σχεδὸν ὀρθότατον αὐτὸ εἶναι, χωρὶς μὲν πολεμικοῦ, χωρὶς δὲ εἰρηνικοῦ θέντας, εἰπεῖν ὡς οὐκ ἔστι πολιτικὸν τοῦτο τῆς ὀρχήσεως τὸ γένος, ἐνταῦθα δὲ κείμενον ἐάσαντας κεῖσθαι, νῦν ἐπὶ τὸ πολεμικὸν ἅμα καὶ εἰρηνικὸν ὡς ἀναμφισβητήτως ἡμέτερον ὂν ἐπανιέναι. So, first of all, we should separate questionable dancing far from dancing that is without controversy. Which is the controversial kind, and how are the two to be distinguished? All the dancing that is of a Bacchic kind and cultivated by those who indulge in intoxicated imitations of Nymphs, Pans, Sileni and Satyrs (as they name them), when performing certain rites of expiation and initiation—this entire class of dancing cannot easily be marked off either as pacific or as warlike, nor as of any one particular kind. The most correct way of defining it appears to me to be this—to place it away from both pacific and warlike dancing, and to pronounce that this type of dancing is οὐ πολιτικόν; having thus set aside and dismissed it, we will now return to the warlike and pacific types, which without controversy belong to us.


Antibodies ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 57 ◽  
Author(s):  
Patrícia de Sousa-Pereira ◽  
Jenny M. Woof

Immunoglobulin A (IgA) plays a key role in defending mucosal surfaces against attack by infectious microorganisms. Such sites present a major site of susceptibility due to their vast surface area and their constant exposure to ingested and inhaled material. The importance of IgA to effective immune defence is signalled by the fact that more IgA is produced than all the other immunoglobulin classes combined. Indeed, IgA is not just the most prevalent antibody class at mucosal sites, but is also present at significant concentrations in serum. The unique structural features of the IgA heavy chain allow IgA to polymerise, resulting in mainly dimeric forms, along with some higher polymers, in secretions. Both serum IgA, which is principally monomeric, and secretory forms of IgA are capable of neutralising and removing pathogens through a range of mechanisms, including triggering the IgA Fc receptor known as FcαRI or CD89 on phagocytes. The effectiveness of these elimination processes is highlighted by the fact that various pathogens have evolved mechanisms to thwart such IgA-mediated clearance. As the structure–function relationships governing the varied capabilities of this immunoglobulin class come into increasingly clear focus, and means to circumvent any inherent limitations are developed, IgA-based monoclonal antibodies are set to emerge as new and potent options in the therapeutic arena.


1998 ◽  
Vol 72 (3) ◽  
pp. 215-219 ◽  
Author(s):  
Ho-Choon Woo ◽  
Myung-Deuk Seo ◽  
Sung-Jong Hong

AbstractCentrocestus armatus (Trematoda: Heterophyidae) develops rapidly and produces eggs at 3 days postinfection in albino rats. Excysted metacercariae are pear-shaped and concave ventrally, with 42–44 peg-like circumoral spines. The entire body surface is densely covered with scale-like serrated spines. On juveniles, serration of the tegumental spines is greatest in the middle of the ventral and dorsal surfaces, and decreases anteriorly and posteriorly. Ciliated sensory papillae are concentrated around the oral sucker. Several nonciliated sensory papillae (type II papillae) occur equidistantly on the acetabulum and are arranged in a linear symmetry on the dorsal surface. On adults, the serration of the tegumental spines decreases to 14–17 tips on the ventrolateral surface. The high density of tegumental spines on posterior half of the body and the distribution of type II papillae on dorsal surface are considered to be characteristic of C. armatus.


2000 ◽  
Vol 68 (7) ◽  
pp. 3830-3839 ◽  
Author(s):  
Dörthe Externest ◽  
Barbara Meckelein ◽  
M. Alexander Schmidt ◽  
Andreas Frey

ABSTRACT Monitoring specific secretory immunoglobulin A (IgA) responses in the intestines after mucosal immunization or infection is impeded by the fact that sampling of small intestinal secretions requires invasive methods not feasible for routine diagnostics. Since IgA plasma cells generated after intragastric immunization are known to populate remote mucosal sites as well, secretory IgA responses at other mucosal surfaces may correlate to those in the intestines and could serve as proxy measures for IgA secretion in the gut. To evaluate the practicability of this approach, mice were immunized intragastrically with 0.2, 2, and 20 mg of ovalbumin plus 10 μg of cholera toxin, and the antigen-specific local secretory IgA responses in duodenal, ileal, jejunal, rectal, and vaginal secretions, saliva, urine, and feces, as well as serum IgG and IgA responses were analyzed by enzyme-linked immunosorbent assay. Correlation analysis revealed significant relationships between serum IgG and IgA, urinary IgA, salivary IgA, and secretory IgA in duodenal, jejunal, ileal, and rectal secretions for the 0.2-mg but not for the 20-mg ovalbumin dose. Fecal samples were poor predictors for intestinal antiovalbumin IgA responses, and no correlations could be established for cholera toxin, neither between local anti-cholera toxin levels nor to the antiovalbumin responses. Thus, specific IgA in serum, saliva, or urine can serve as a predictor of the release of specific IgA at intestinal surfaces after intragastric immunization, but the lack of correlations for high ovalbumin doses and for cholera toxin indicates a strong dependency on antigen type and dosage for these relationships.


2021 ◽  
Author(s):  
Haowen Zhang ◽  
Ce Qi ◽  
Yuning Zhao ◽  
Mengyao Lu ◽  
Xinyue Li ◽  
...  

Gestational diabetes mellitus (GDM) may be related to intestinal mucosal damage and inflammation-induced dysbiosis of secretory IgA (SIgA) coated microbiota. SIgA coated L. reuteri can reduce the level of inflammation of GDM in vitro.


Author(s):  
F.M.S. Lima ◽  
G.M. Venceslau ◽  
G.T. Brasil

In hydrostatics, the Archimedes principle predicts an upward force whenever a body is submerged in a liquid. In contrast to common sense, this physical law is not free of exceptions, as for example when the body touches the container. This is more evident when a rectangular block less dense than the liquid rests on the bottom, with no liquid underneath it, a case in which a downward force is expected, according to a recent work by the first author. In the present work, we describe a simple, low-cost experiment which allows the detection of such force. This counterintuitive result shows the inadequacy of Archimedes' principle for treating "contact" cases.


2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Anouk K. Gloudemans ◽  
Bart N. Lambrecht ◽  
Hermelijn H. Smits

Allergic asthma is characterized by bronchial hyperresponsiveness, a defective barrier function, and eosinophilic lower airway inflammation in response to allergens. The inflammation is dominated by Th2 cells and IgE molecules and supplemented with Th17 cells in severe asthma. In contrast, in healthy individuals, allergen-specific IgA and IgG4 molecules are found but no IgE, and their T cells fail to proliferate in response to allergens, probably because of the development of regulatory processes that actively suppress responses to allergens. The presence of allergen-specific secretory IgA has drawn little attention so far, although a few epidemiological studies point at a reverse association between IgA levels and the incidence of allergic airway disease. This review highlights the latest literature on the role of mucosal IgA in protection against allergic airway disease, the mechanisms described to induce secretory IgA, and the role of (mucosal) dendritic cells in this process. Finally, we discuss how this information can be used to translate into the development of new therapies for allergic diseases based on, or supplemented with, IgA boosting strategies.


2018 ◽  
Vol 11 (1) ◽  
pp. 34
Author(s):  
Alfan Farizki Wicaksono ◽  
Sharon Raissa Herdiyana ◽  
Mirna Adriani

Someone's understanding and stance on a particular controversial topic can be influenced by daily news or articles he consume everyday. Unfortunately, readers usually do not realize that they are reading controversial articles. In this paper, we address the problem of automatically detecting controversial article from citizen journalism media. To solve the problem, we employ a supervised machine learning approach with several hand-crafted features that exploits linguistic information, meta-data of an article, structural information in the commentary section, and sentiment expressed inside the body of an article. The experimental results shows that our proposed method manages to perform the addressed task effectively. The best performance so far is achieved when we use all proposed feature with Logistic Regression as our model (82.89\% in terms of accuracy). Moreover, we found that information from commentary section (structural features) contributes most to the classification task.


2021 ◽  
Vol 12 (1) ◽  
pp. 96-102
Author(s):  
E. A. Flerova

At present, special attention is drawn to the study of the adaptation of aquatic organisms to a complex of environmental factors precisely at the cellular level. It is very important to study the structural and functional features of the kidney, which not only plays a key role in osmoregulation, but also makes a significant contribution to maintaining homeostasis at the level of functioning of a single nonspecific defense system of the body. In this aspect, the study of species belonging to a unique ancient group, united in the order salmoniformes, is highly relevant. Using the methods of light and electron microscopy, we investigated the morphology and ultrastructure of the mesonephros of the population of the semianadromous ecological form European smelt Osmerus eperlanus inhabiting the Gulf of Finland of the Baltic Sea and performing spawning migrations in the Luga River of the Leningrad Region. The general scheme of the trunk kidney organization is given, the structural features and the ratio of leukocytes and structures of the smelt nephron are revealed. It is shown that the development of hematopoietic tissue in the mesonephros, the number of mature forms of granulocytes are systematic signs which do not depend on the ecology of the species. The ratio of leukocytes, the width of the cisterns of the rough endoplasmic reticulum of plasma cells, the structure and number of granules in granulocytes are associated with the peculiarities of the functioning of the cellular link of the immune system under certain conditions of the species habitat. The ultrafine structure of the ion-transporting interstitial cells, as well as the ultrastructural features found in the smelt nephron, can be considered cytological markers of smelt adaptation to a semianadromous lifestyle.


Author(s):  
Shelby C. Inbody ◽  
Bridgett E Sinquefield ◽  
Joshua P. Lewis ◽  
Renita E. Horton

Tissue culture platforms have been around for several decades and have enabled numerous key findings in the cardiovascular field. However, these platforms fail to recreate the mechanical and dynamic features found within the body. Organs-on-chips (OOCs) are cellularized microfluidic based devices that can mimic the basic structure, function, and responses of organs. These systems have been successfully utilized in disease, development, and drug studies. OOCs are designed to recapitulate the mechanical, electrical, chemical, and structural features of the in vivo microenvironment. Here, we review cardiovascular-themed OOC studies, design considerations, and techniques used to generate microtissues within these devices. Further, we will highlight the advantages of OOCs over traditional cell culture methods, discuss implementation challenges, and provide perspectives on the state of the field.


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