IFNβ, interferon beta; IFNγ, interferon gamma; IL, interleukin; Acod1/Irg1: aconitate decarboxylase 1/immune-responsive gene 1; KEAP1, Kelch-like ECH-associated protein 1; LPS, lipopolysaccharide; ...LTx, leukotriene; MHC, major histocompatibility complex; mtROS, mitochondria-derived reactive oxygen species; NRF2, nuclear factor erythroid 2–related factor 2; OxPhos, oxidative phosphorylation; PG, prostaglandin; SDH/CII, succinate dehydrogenase and complex II of the respiratory chain; TCA cycle, tricarboxylic acid cycle. https://doi.org/10.1371/journal.ppat.1010361.g001 Is itaconate antimicrobial? From the mitochondrial matrix, itaconate is transported into the cytosol where it can regulate metabolism at the glycolysis step, inhibiting key enzymes in this pathway to decrease glycolysis 20. ...itaconate mediates several of the metabolic changes during inflammation; these direct effects are observed in most in vitro inflammatory models. Curiously, neurons are able to take up exogenous itaconate, and itaconate application improved neurological function upon reperfusion injury 28. ...itaconate can control tissue function by acting on nonmyeloid cells. ...it is still unclear which immune signal is influencing this differential recruitment and whether itaconate may influence the development of adaptive immunity. ...far, a single study observed that itaconate
In the past few years, fungal diseases caused estimated over 1.6 million deaths annually and over one billion people suffer from severe fungal diseases (Brown et al., 2012; Anonymous, 2017b). Public ...health surveillance of fungal diseases is generally not compulsory, suggesting that most estimates are conservative (Casadevall, 2017; Anonymous, 2017a). Fungal disease can also damage plants and crops, causing major losses in agricultural activities and food production (Savary et al., 2012). Animal pathogenic fungi are threatening bats, amphibians and reptiles with extinction (Casadevall, 2017). It is estimated that fungi are the highest threat for animal-host and plant-host species, representing the major cause (approximately 65%) of pathogen-driven host loss (Fisher et al., 2012). In this complex scenario, it is now clear that the global warming and accompanying climate changes have resulted in increased incidence of many fungal diseases (Garcia-Solache and Casadevall, 2010). On the basis of all these factors, concerns on the occurrence of a pandemic of fungal origin in a near future have been raised (Casadevall, 2017). In this context, to stop forgetting and underestimating fungal diseases is mandatory.
Summary
Half a century after the introduction of Amphotericin B the management of cryptococcosis remains unsatisfactory. The disease, caused primarily by the two fungal species Cryptococcus ...neoformans and Cryptococcus gattii, remains responsible for considerable morbidity and mortality despite standard medical care. Current therapeutic options are limited to Amphotericin B, azoles and 5‐flucytosine. However, this organism has numerous well‐characterized virulence mechanisms that are amenable to pharmacological interference and are thus potential therapeutic targets. Here, we discuss existing approved antifungal drugs, resistance mechanisms to these drugs and non‐standard antifungal drugs that have potential in treatment of cryptococcosis, including immunomodulatory strategies that synergize with antifungal drugs, such as cytokine administration or monoclonal antibodies. Finally, we summarize attempts to target well‐described virulence factors of Cryptococcus, the capsule or fungal melanin. This review emphasizes the pressing need for new therapeutic alternatives for cryptococcosis.
This systematic review of the literature aims to evaluate possible associations between moral judgment and hormones. The electronic databases PsycINFO, PubMed, Scielo, Web of Science, Scopus, and ...LILACS were used. Twenty studies with different methodological designs were reviewed, covering the hormones cortisol, oxytocin, and testosterone, assessing aspects related to polymorphisms in receptor genes, endogenous levels, and exogenous administration. Taken together, the reviewed studies showed a trend towards an association between hormones and moral judgment, with important specificities involving biological, environmental, and individual aspects. Endogenous levels of cortisol, released under stress, showed negative associations with altruistic and utilitarian decisions only in highly emotionally charged dilemmas. Oxytocin receptor gene polymorphisms (rs2268498, rs237889, and rs2254298) and acute administration of this hormone were associated with variability in moral judgment, with sex as an important moderating variable. Testosterone studies have tended to show a positive association with utilitarian moral judgments, particularly in female and in individuals with low prenatal exposure to this hormone. Knowing how hormones influence moral judgment may help expand our understanding of the plurality of human behavior. However, this area of research is new and still little explored, which does not allow for conclusions with a high level of evidence. Subsequent research will benefit from methodological improvements to extend current findings.
Of the thousands of per- and polyfluoroalkyl substances (PFAS) known to exist, only a small fraction (≤1%) are commonly monitored in humans. This discrepancy has led to concerns that human exposure ...may be underestimated. Here, we address this problem by applying a comprehensive fluorine mass balance (FMB) approach, including total fluorine (TF), extractable organic fluorine (EOF), total oxidizable precursors (TOP), and selected target PFAS, to human serum samples collected over a period of 28 years (1986, 2007, and 2015) in Tromsø, Norway. While concentrations of TF did not change between sampling years, EOF was significantly higher in 1986 compared to 2007 and 2015. The ∑12PFAS concentrations were highest in 2007 compared to 1986 and 2015, and unidentified EOF (UEOF) decreased from 1986 (46%) to 2007 (10%) and then increased in 2015 (37%). While TF and EOF were not influenced by sex, women had higher UEOF compared to men, opposite to target PFAS. This is the first FMB in human serum to include TOP, and it suggests that precursors with >4 perfluorinated carbon atoms make a minor contribution to EOF (0–4%). Additional tools are therefore needed to identify substances contributing to the UEOF in human serum.
is not usually considered a cytotoxic fungal pathogen but there is considerable evidence that this microbe can damage host cells and tissues. In this essay, we review the evidence that
damages host ...cells and note that the mechanisms involved are diverse. We consider
-mediated host damage at the molecular, cellular, tissue, and organism level. Direct mechanisms of cytotoxicity include lytic exocytosis, organelle dysfunction, phagolysosomal membrane damage, and cytoskeletal alterations. Cytotoxicity contributes to pathogenesis by interfering with immune effector cell function and disrupting endothelial barriers thus allowing dissemination. When
-mediated and immune-mediated host damage is sufficient to affect homeostasis, cryptococcosis occurs at the organism level.
Cryptococcus neoformans is a fungal pathogen with worldwide distribution. Serological studies of human populations show a high prevalence of human infection, which rarely progresses to disease in ...immunocompetent hosts. However, decreased host immunity places individuals at high risk for cryptococcal disease. The disease can result from acute infection or reactivation of latent infection, in which yeasts within granulomas and host macrophages emerge to cause disease. In this review, we summarize what is known about the cellular recognition, ingestion, and killing of C. neoformans and discuss the unique and remarkable features of its intracellular life, including the proposed mechanisms for fungal persistence and killing in phagocytic cells.
Tupí-Guaraní is one of the largest branches of the Tupían language family, but despite its relevance there is no consensus about its origins in terms of age, homeland, and expansion. Linguistic ...classifications vary significantly, with archaeological studies suggesting incompatible date ranges while ethnographic literature confirms the close similarities as a result of continuous inter-family contact. To investigate this issue, we use a linguistic database of cognate data, employing Bayesian phylogenetic methods to infer a dated tree and to build a phylogeographic expansion model. Results suggest that the branch originated around 2500 BP in the area of the upper course of the Tapajós-Xingu basins, with a split between Southern and Northern varieties beginning around 1750 BP. We analyse the difficulties in reconciling archaeological and linguistic data for this group, stressing the importance of developing an interdisciplinary unified model that incorporates evidence from both disciplines.
Small immune complexes cause type III hypersensitivity reactions that frequently result in tissue injury. The responsible mechanisms, however, remain unclear and differ depending on target organs. ...Here, we identify a kidney-specific anatomical and functional unit, formed by resident macrophages and peritubular capillary endothelial cells, which monitors the transport of proteins and particles ranging from 20 to 700 kDa or 10 to 200 nm into the kidney interstitium. Kidney-resident macrophages detect and scavenge circulating immune complexes “pumped” into the interstitium via trans-endothelial transport and trigger a FcγRIV-dependent inflammatory response and the recruitment of monocytes and neutrophils. In addition, FcγRIV and TLR pathways synergistically “super-activate” kidney macrophages when immune complexes contain a nucleic acid. These data identify a physiological function of tissue-resident kidney macrophages and a basic mechanism by which they initiate the inflammatory response to small immune complexes in the kidney.
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•Kidney macrophages (KM) are a resident population•KM are located at the abluminal side of peritubular capillaries•A unique function of KM is to monitor endothelial transport•Scavenging of immune complexes by KM triggers type III hypersensitivity
Kidney-resident macrophages and endothelial cells form an anatomical and functional unit that monitors the transport of proteins and particles according to their size and enables immediate detection of potential threats.
Diário de uma iniciação à docência Cosentino, Anna Carolina Coelho
Revista Educação, Artes e Inclusão,
12/2023, Letnik:
19, Številka:
1
Journal Article
Recenzirano
Odprti dostop
No presente texto apresento inquietudes e reflexões emergentes na minha primeira prática docente em educação artística, realizada no ano letivo 2019/2020 em uma escola pública de Portugal. O trabalho ...foi desenvolvido com 05 turmas da componente curricular artes performativas, com crianças de 03 a 09 anos de idade e fundamentação teórica principalmente a partir de Viola Spolin (2008, 2010) e Augusto Boal (2005). No decorrer do referido ano letivo os primeiros dois meses de trabalho foram os mais difíceis. O principal desafio foi conciliar o que eu pensava que fosse interessante para os estudantes com o que eles traziam, propunham, desejavam - com quem eles são. Esta passou a ser a minha prática: estar com os ouvidos, o coração e a sensorialidade abertos para sentir como chegavam em cada um dos nossos encontros e a partir desta percepção buscar uma interação com os mesmos. Muitas vezes esta iniciativa foi “mal sucedida” no sentido de que não conseguimos produzir o que tecnicamente se chamaria de aula. Com a presente escrita apenas organizo o que foi feito de modo a começar a perceber onde me situo, no campo da educação artística.
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