493 research outputs found
Microbiota-host communications: Bacterial extracellular vesicles as a common language
No full textBoth gram-negative and gram-positive bacteria release extracellular vesicles (EVs) that contain components from their mother cells. Bacterial EVs are similar in size to mammalian-derived EVs and are thought to mediate bacteria-host communications by transporting diverse bioactive molecules including proteins, nucleic acids, lipids, and metabolites. Bacterial EVs have been implicated in bacteria-bacteria and bacteria-host interactions, promoting health or causing various pathologies. Although the science of bacterial EVs is less developed than that of eukaryotic EVs, the number of studies on bacterial EVs is continuously increasing. This review highlights the current state of knowledge in the rapidly evolving field of bacterial EV science, focusing on their discovery, isolation, biogenesis, and more specifically on their role in microbiota-host communications. Knowledge of these mechanisms may be translated into new therapeutics and diagnostics based on bacterial EVs
Vaginal Lactobacillus Inhibits HIV-1 Replication in Human Tissues Ex Vivo
No full textLactobacillus species, which dominate vaginal microbiota of healthy reproductive-age women, lower the risks of sexually transmitted infections, including the risk of human immunodeficiency virus (HIV) acquisition. The exact mechanisms of this protection remain to be understood. Here, we investigated these mechanisms in the context of human cervico-vaginal and lymphoid tissues ex vivo. We found that all six Lactobacillus strains tested in these systems significantly suppressed HIV type-1 (HIV-1) infection. We identified at least three factors that mediated this suppression: (i) Acidification of the medium. The pH of the undiluted medium conditioned by lactobacilli was between 3.8 and 4.6. Acidification of the culture medium with hydrochloric acid (HCl) to this pH in control experiments was sufficient to abrogate HIV-1 replication. However, the pH of the Lactobacillus-conditioned medium (CM) diluted fivefold, which reached ∼6.9, was also suppressive for HIV-1 infection, while in control experiments HIV-1 infection was not abrogated when the pH of the medium was brought to 6.9 through the use of HCl. This suggested the existence of other factors responsible for HIV-1 inhibition by lactobacilli. (ii) Lactic acid. There was a correlation between the concentration of lactic acid in the Lactobacillus-CM and its ability to suppress HIV-1 infection in human tissues ex vivo. Addition of lactic acid isomers D and L to tissue culture medium at the concentration that corresponded to their amount released by lactobacilli resulted in HIV-1 inhibition. Isomer L was produced in higher quantities than isomer D and was mostly responsible for HIV-1 inhibition. These results indicate that lactic acid, in particular its L-isomer, inhibits HIV-1 independently of lowering of the pH. (iii) Virucidal effect. Incubation of HIV-1 in Lactobacillus-CM significantly suppressed viral infectivity for human tissues ex vivo. Finally, lactobacilli adsorb HIV-1, serving as a sink decreasing the number of free virions. In summary, we found that lactobacilli inhibit HIV-1 replication in human tissue ex vivo by multiple mechanisms. Further studies are needed to evaluate the potential of altering the spectra of vaginal microbiota as an effective strategy to enhance vaginal health. Human tissues ex vivo may serve as a test system for these strategies
On the Meanings and Implications of Joseph Margolis’ Definition of Art
No full textThis paper develops an inquiry into the meanings and implications of Joseph Margolis’ definition of artworks as physically embodied and culturally emergent entities. It starts from the pars destruens of his theory, by comparing two different texts criticizing Morris Weitz’ denial of the possibility to define art. While in an early essay Margolis is ready to accept a constructivistic conception of necessary and sufficient conditions, six decades later he seems to have dropped the attempt to maintain a deflationary version of enabling conditions in view of a more coherent form of contingentism and pluralism. Secondly, the paper focuses on the “generic” character of Margolis’ definition, namely its being too inclusive, insofar as it fits any kind of cultural entity. The author suggests that the first implication of Margolis’ “generic” definition is the idea of continuity between artworks and the things and events of the cultural world. A second implication is that according to Margolis differences between artworks and other things can only be traced a posteriori, by looking at collective practices and at habitual uses of the term. Finally, the author argues that Margolis’ radically historicist and contextualized approach to the arts should be integrated through a coherent historicizing and contextualizing of the very issue of the definition of art. A similar step could have strengthened his transition to a more inclusive philosophy of culture and philosophical anthropology
Extracellular Vesicles Generated by Gram-Positive Bacteria Protect Human Tissues Ex Vivo From HIV-1 Infection
No full textVaginal microbiota dominated by lactobacilli protects women from sexually transmitted infection, in particular HIV-1. This protection is, in part, mediated by Lactobacillus-released extracellular vesicles (EVs). Here, we investigated whether EVs derived from other Gram-positive bacteria also present in healthy vaginas, in particular Staphylococcus aureus, Gardnerella vaginalis, Enterococcus faecium, and Enterococcus faecalis, can affect vaginal HIV-1 infection. We found that EVs released by these bacteria protect human cervico-vaginal tissues ex vivo and isolated cells from HIV-1 infection by inhibiting HIV-1-cell receptor interactions. This inhibition was associated with a diminished exposure of viral Env by steric hindrance of gp120 or gp120 modification evidenced by the failure of EV-treated virions to bind to nanoparticle-coupled anti-Env antibodies. Furthermore, we found that protein components associated with EV’s outer surface are critical for EV-mediated protection from HIV-1 infection since treatment of bacteria-released EVs with proteinase K abolished their anti-HIV-1 effect. We identified numerous EV-associated proteins that may be involved in this protection. The identification of EVs with specific proteins that suppress HIV-1 may lead to the development of novel strategies for the prevention of HIV-1 transmission
Willingness to participate in HIV research at the end of life (EOL).
No full textIntroductionAnimal models have been vital for scientific discovery but have limitations, especially in infectious disease research. It is essential to develop a means to study these diseases in human models. We hypothesized that altruistic people would willingly participate in research near the end-of-life (EOL), for the benefit of science and to provide one last gift to society.MethodologyTwo surveys were administered to 377 self-reported HIV-negative and 96 HIV-positive individuals. Hypothetical questions assessed their willingness to participate in altruistic research in the last 6 months of life, which might result in a shortened lifespan or physical discomforts. The self-reported HIV-negative group was also asked about willingness to be exposed to infectious pathogens for the sake of research.ResultsAlmost all responders expressed willingness to participate in research at the EOL, regardless of HIV-status. The majority of participants were willing to endure physical discomfort for the sake of research. 'Blood draws' was identified as the most tolerable physical discomfort (>70% in both groups). In both groups, >60% were willing to shorten their lifespans for the sake of research. A third of the self-reported HIV-negative group expressed willingness to be exposed to at least one infectious agent to participate in EOL research.ConclusionsOur exploratory study demonstrates that people would welcome the opportunity to participate in altruistic research near the EOL. Such research could greatly impact the way infectious disease research is conducted. This study is limited however by its hypothetical nature. Further research is necessary to confirm this interest in those with terminal illness before any further clinical research effort at the EOL can be performed
Pedagogical Education as the Development of Initial Pedagogical Ideas
No full textThe article examines the role of initial pedagogical beliefs held by students in teacher training programs as they begin to engage with pedagogical education curricula. It highlights the significance of school experiences in shaping these beliefs. The article analyzes the reasons for their sustainability during the subsequent acquisition of the educational program by future educators at the university level. The author argues for the necessity of designing teacher training programs in the form of a sequential and specially organized transformation of initial pedagogical beliefs, aimed at fostering conceptual change and developing the practical thinking of future educators.</p
HIV: from molecular recognition to tissue pathogenesis
No full textAbstractDramatic progress has been made recently in identifying both viral and cellular molecules responsible for binding and fusion of HIV-1 to target cells. In vivo, HIV-1 infection is transmitted by viruses that recognize chemokine receptor CCR5, while viruses isolated at later stages of HIV disease often recognize another chemokine receptor, CXCR4. It is still not understood how this molecular tropism of HIV-1 is translated into the virus' ability to compromise normal cell functions, which results in impairment of lymphoid tissue and causes AIDS. Here, we discuss how the new molecular findings might relate to HIV pathogenesis in cells and tissues
Immunoactivation at the Crossroads of Human Disease
No full textAbstractIt is becoming increasingly clear that immunoactivation, which evolved as a system of host defense against pathogens, can become dysregulated and promote the pathogenesis of diverse diseases with both known and unknown etiologies (eg, acquired immune deficiency syndrome, age-related macular degeneration, cancer, as well as aging). Immunoactivation seems to be a “common denominator” or general mechanism of pathogenesis and may explain the association and similarities in pathology among otherwise unrelated human diseases. Identification of general mechanisms of immunoactivation may lead to the development of new therapeutic strategies applicable to many diseases even before detailed knowledge of specific etiology and pathogenesis may be available
Interleukin-7 Facilitates HIV-1 Transmission to Cervico-Vaginal Tissue ex vivo
No full textThe majority of HIV-1 infections in women occur through vaginal intercourse, in which virus-containing semen is deposited on the cervico-vaginal mucosa. Semen is more than a mere carrier of HIV-1, since it contains many biological factors, in particular cytokines, that may affect HIV-1 transmission. The concentration of interleukin (IL)-7, one of the most prominent cytokines in semen of healthy individuals, is further increased in semen of HIV-1-infected men. Here, we investigated the potential role of IL-7 in HIV-1 vaginal transmission in an ex vivo system of human cervico-vaginal tissue. We simulated an in vivo situation by depositing HIV-1 on cervico-vaginal tissue in combination with IL-7 at concentrations comparable with those measured in semen of HIV-1-infected individuals. We found that IL-7 significantly enhanced virus replication in ex vivo infected cervico-vaginal tissue. Similarly, we observed an enhancement of HIV-1 replication in lymphoid tissue explants. Analysis of T cells isolated from infected tissues showed that IL-7 reduced CD4+ T cell depletion preventing apoptosis, as shown by the decrease in the number of cells expressing the apoptotic marker APO2.7 and the increase in the expression of the anti-apoptotic protein B-cell lymphoma (Bcl)-2. Also, IL-7 increased the fraction of cycling CD4+ T cells, as evidenced by staining for the nuclear factor Ki-67. High levels of seminal IL-7 in vivo may be relevant to the survival of the founder pool of HIV-1-infected cells in the cervico-vaginal mucosa at the initial stage of infection, promoting local expansion and dissemination of HIV infection
It Takes More Than Two for This Tango
No full textA paper in this issue by Ogawa et al. (2013) shows that HSV-2-infected keratinocytes in human skin explants release a protein that enhances HIV-1 infection of Langerhans cells in vitro. This may explain the in vivo observation that HSV-2 infection facilitates HIV-1 acquisition
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