Schistosomiasis is a major cause of morbidity in humans invoked by chronic infection with parasitic trematodes of the genus Schistosoma. Schistosomes have a complex life-cycle involving infections of ...an aquatic snail intermediate host and a definitive mammalian host. In humans, adult male and female worms lie within the vasculature. Here, they propagate and eggs are laid. These eggs must then be released from the host to continue the life cycle.
and
reside in the mesenteric circulation of the intestines with egg excreted in the feces. In contrast,
are present in the venus plexus of the bladder, expelling eggs in the urine. In an impressive case of exploitation of the host immune system, this process of Schistosome "eggs-iting" the host is immune dependent. In this article, we review the formation of the egg granuloma and explore how
eggs laid in vasculature must usurp immunity to induce regulated inflammation, to facilitate extravasation through the intestinal wall and to be expelled in the feces. We highlight the roles of immune cell populations, stromal factors, and egg secretions in the process of egg excretion to provide a comprehensive overview of the current state of knowledge regarding a vastly unexplored mechanism.
Accurate depiction of visual information presents a formidable obstacle to the inclusion of people with visual impairments in standardized educational assessment. This challenge is often addressed by ...using tactile graphics, such as the use of a collection of tactile patterns representing various zones similar to the use of colors to represent political boundaries on a visual map. This study investigated friction mechanisms involved during fingertip exploration of tactile graphics, as well as the role that friction played in forming perceptions. Perception experiments were run using four texture types published by the Braille Authority of North America (BANA): two parallel-ridge textures of different ridge widths and spacings, and two ordered-dot textures of different dot spacings. To minimize tactile confusion, BANA guidelines prohibit the use of similar textures adjacent to each other. In this study, texture pairs were printed adjacent to each other on thermally activated (‘swell touch’) tactile paper. Sighted human subjects participated in a blinded task of determining if the two textures in the pair were the same or different. Friction measurements of the fingertip exploration of the texture pairs was recorded using a dynamometer in a range of normal loads from 0.4 to 0.8 N. A generalized linear model (GLM) with a logistic link function was used to predict the influence of texture pair and participant on the likelihood of perceiving each texture pair as the same or different. Results showed that the particular texture pair had a strong correlation to the ability of participants to discern between textures. These quantitative results support the BANA guidelines. The friction data showed that there was not a significant amount of difference among the coefficients of friction of various textures, such that COF was not a strong predictor of perceptive ability. However, there was some evidence that penetration of the fingertip between raised texture elements, and interlocking with these elements, allowed for dissimilar dot patterns to be better discerned than dissimilar ridge patterns. The results indicate that there are other aspects, possibly still tribological in nature, that govern tactile perception when exploring tactile graphics. These phenomena may include such things as finger deformation and vibrational response produced during contact with individual texture elements.
•Psychophysical studies were done on sighted people to evaluate the tactile discrimination of tactile graphic textures.•The probability of discerning textures was well predicted using the General Linear Model with a logistic link function.•Sequence order effects in similar ridged textures appeared to be related to finger penetration into the textures.•The ability to discern between these texture types did not appear to be strongly influenced by coefficient of friction.
The high and lows of type 2 asthma and mouse models Fallon, Padraic G.; Schwartz, Christian
Journal of allergy and clinical immunology,
February 2020, 2020-02-00, 20200201, Letnik:
145, Številka:
2
Journal Article
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Back in 1989 some studies have shown that the viral protein Vpr was dispensable for HIV-1 replication in vitro. From then the concept of accessory or auxiliary protein for Vpr has ...emerged and it is still used to date. However, Vpr soon appeared to be very important for in vivo virus spread and pathogenesis. Vpr has been involved in many biological functions including regulation of reverse transcriptase activity, the nuclear import of the pre-integration complex (PIC), HIV-1 transcription, gene splicing, apoptosis and in cell cycle arrest. Thus, we might rather consider Vpr as a true virulence factor instead of just an accessory factor. At present, Vpr can be regarded as a potential and promising target in different strategies aiming to fight infected cells including latently infected cells.
A considerable number of total-joint replacement devices used in orthopaedic medicine involve articulation between a metallic alloy and ultra-high molecular weight polyethylene (UHMWPE). Though this ...polymer has excellent wear resistance, the wear particulate that is produced leads to the limited lifetime of the devices—osteolytic bone loss. Crosslinking has been shown to reduce the wear rate of UHMWPE, but can cause a reduction in various mechanical properties such as impact toughness. Previous work by the authors has shown that UHMWPE-based composites have wear resistance comparable to the irradiation-crosslinked polymer. However, the selection of the reinforcing material is complicated both by understanding the mechanical behavior of the filler and also by biocompatibility considerations. Zirconium has been shown to have excellent corrosion resistance and biocompatibility, and the authors have used the material as a reinforcing filler in UHMWPE with promising results. Compression-molded UHMWPE composites with up to 20
wt.% of microsized zirconium particles were investigated with regards to wear behavior and impact toughness. These composites showed a significant reduction in wear compared to unfilled polymer while still maintaining impact toughness. These results reinforce the paradigm of using polymer composites for orthopaedic applications and may provide a viable alternative to the property tradeoffs encountered with irradiation crosslinking.
Basophils are associated with T helper 2 (Th2) cell-polarized immune responses such as allergic disorders or helminth infections. To directly address the role of basophils for type 2 immunity, we ...generated transgenic mice with constitutive and selective deletion of basophils. Differentiation and accumulation of Th2 cells, induction of eosinophilia, and increase in serum IgE or IgG1 induced by allergens or by infection with the helminth
Nippostrongylus brasiliensis appeared to be basophil independent. Further, basophils were not required for passive IgE- or IgG1-mediated systemic anaphylaxis. However, basophils were essential for IgE-meditated chronic allergic dermatitis and for protection against secondary infection with
N. brasiliensis. These results demonstrate that basophils play an important role for protective immunity against helminths and orchestrate chronic allergic inflammation, whereas primary Th2 cell responses can operate efficiently in the absence of this cell type.
► Constitutively basophil-ablated mice show normal Th2 responses ► Chronic allergic dermatitis depends on basophils ► Basophils are not required for humoral immune responses ► Basophils mediate protective immunity against secondary helminth infections
Despite efficient combination of the antiretroviral therapy (cART), which significantly decreased mortality and morbidity of HIV-1 infection, a definitive HIV cure has not been achieved. Hidden HIV-1 ...in cellular and anatomic reservoirs is the major hurdle toward a functional cure. Microglial cells, the Central Nervous system (CNS) resident macrophages, are one of the major cellular reservoirs of latent HIV-1. These cells are believed to be involved in the emergence of drugs resistance and reseeding peripheral tissues. Moreover, these long-life reservoirs are also involved in the development of HIV-1-associated neurocognitive diseases (HAND). Clearing these infected cells from the brain is therefore crucial to achieve a cure. However, many characteristics of microglial cells and the CNS hinder the eradication of these brain reservoirs. Better understandings of the specific molecular mechanisms of HIV-1 latency in microglial cells should help to design new molecules and new strategies preventing HAND and achieving HIV cure. Moreover, new strategies are needed to circumvent the limitations associated to anatomical sanctuaries with barriers such as the blood brain barrier (BBB) that reduce the access of drugs.
The introduction of the highly active antiretroviral therapy (HAART) has greatly improved survival. However, these treatments fail to definitively cure the patients and unveil the presence of ...quiescent HIV-1 reservoirs like cells from monocyte-macrophage lineage. A purge, or at least a significant reduction of these long lived HIV-1 reservoirs will be needed to raise the hope of the viral eradication. This review focuses on the molecular mechanisms responsible for viral persistence in cells of the monocyte-macrophage lineage. Controversy on latency and/or cryptic chronic replication will be specifically evoked. In addition, since HIV-1 infected monocyte-macrophage cells appear to be more resistant to apoptosis, this obstacle to the viral eradication will be discussed. Understanding the intimate mechanisms of HIV-1 persistence is a prerequisite to devise new and original therapies aiming to achieve viral eradication.
A high intake of dietary salt (NaCl) has been implicated in the development of hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that salt has a proinflammatory ...effect and boosts the activation of Th17 cells and the activation of classical, LPS-induced macrophages (M1). Here, we examined how the activation of alternative (M2) macrophages is affected by salt. In stark contrast to Th17 cells and M1 macrophages, high salt blunted the alternative activation of BM-derived mouse macrophages stimulated with IL-4 and IL-13, M(IL-4+IL-13) macrophages. Salt-induced reduction of M(IL-4+IL-13) activation was not associated with increased polarization toward a proinflammatory M1 phenotype. In vitro, high salt decreased the ability of M(IL-4+IL-13) macrophages to suppress effector T cell proliferation. Moreover, mice fed a high salt diet exhibited reduced M2 activation following chitin injection and delayed wound healing compared with control animals. We further identified a high salt-induced reduction in glycolysis and mitochondrial metabolic output, coupled with blunted AKT and mTOR signaling, which indicates a mechanism by which NaCl inhibits full M2 macrophage activation. Collectively, this study provides evidence that high salt reduces noninflammatory innate immune cell activation and may thus lead to an overall imbalance in immune homeostasis.
Significance Gastrointestinal worms (helminths) infect more than 2 billion people, and vaccines are not yet available. Helminths elicit a type 2 immune response characterized by high serum IgE levels ...and increased numbers of IL-4– or IL-13–secreting effector cells including Th2 cells, eosinophils, basophils, and type 2 innate lymphoid cells. We determined the mechanism by which basophils contribute to protection against secondary infections with gastrointestinal helminths. Here we demonstrate that basophils are recruited into the small intestine of infected mice and orchestrate the local type 2 immune response in this tissue. Basophil-mediated protection required the presence of IgE and the expression of activating Fc receptors and IL-4/IL-13 in basophils. These findings could help the development of new vaccination strategies against helminths.
Basophils orchestrate protection against reinfections with gastrointestinal helminths and ticks, but the underlying mechanisms remain elusive. We investigated the role of Fc receptors on basophils, the antibody isotypes IgG1 and IgE, and basophil-derived IL-4/IL-13 during challenge infections with Heligmosomoides polygyrus and Nippostrongylus brasiliensis . Using mixed bone marrow chimeras, we found that activating Fc receptors on basophils were required for protective immunity but not for regulation of basophil homeostasis. Furthermore, rapid worm expulsion was impaired in IgE-deficient but not in IgG1-deficient mice. Basophils promoted the recruitment of other effector cells into the small intestine and induced expression of the antihelminthic proteins resistin-like molecule β and mucin 5ac. Selective deletion of IL-4/IL-13 in basophils resulted in impaired worm expulsion. Collectively, our results indicate that IgE-mediated activation of basophils and the release of basophil-derived IL-4/IL-13 are critical steps in protective immunity against helminths. Therefore, development of effective vaccines against helminths should consider boosting the IL-4/IgE/basophil axis of the immune system.
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