196,030 research outputs found
Pneumococcal interactions with the host : threats and therapeutic approaches
No full textStreptococcus pneumoniae (the pneumococcus) is a Gram-positive bacterium responsible for substantial morbidity and mortality worldwide. Apart from causing severe pneumonia, septicemia or meningitis, pneumococci are also major contributors to less severe diseases like otitis media and sinusitis. Pneumococcal autolysis was thought to be the main route that S. pneumoniae utilizes in order to deliver its virulence factors. Recently a new mechanism has been proposed, the release of extracellular vesicles (EVs).Presence of adhesins and other virulence factors on EVs leads to cell responses after contact with vesicles. We observed that pneumococcal EVs are indeed a mechanism for the delivery of virulence factors to host cells, and that interactions of vesicles with dendritic cells lead to activation of cells and release of pro-inflammatory cytokines. Since EVs mimic the outside of a bacterium, they can play a role as decoys for the immune system. Tightly linked to this decoy function is the ability of EVs to promote immune evasion through binding of serum components. Indeed, we discovered that pneumococcal EVs are able to bind several components of the human complement system, leading to formation of the membrane attack complex on vesicles.Outer membrane vesicles (OMVs) released from Gram-negative bacteria have been directly used as vaccines in numerous preclinical mouse models. We isolated pneumococcal vesicles and found that they are able to confer serotype-independent protection in mice. Moreover, these vesicles stimulate the production of antibodies directed against pneumococcal antigens. These antibodies are able to increase opsonophagocytosis of pneumococci by mouse macrophages, and are required for protection, as demonstrated by the absence of protection in mice that are not able to produce B lymphocytes. Moreover, in our model the vesicles are able to protect mice against an infection with a pneumococcal strain of serotype 3, to a higher degree than what we observed for the currently available pneumococcal vaccine PCV13. The protective effect in humans of PCV13 against IPD caused by serotype 3 is debated.The structure of the pneumococcal capsule differs vastly between serotypes. We found that these differences have profound consequences in determining the disease progression in terms of pneumonia or septicemia, in mice. In particular, we observed that serotype 2 was quickly cleared from the lungs but migrated efficiently to the blood, while serotype 3 remained in the lungs, since the thick capsule made bacteria able to adhere less to cells and better avoid opsonization by the complement system. Fate of pneumococcal disease is tightly linked to the immune response against pneumococci. We found that a compound used in traditional Chinese medicine is able to potentiate the response of dendritic cells against pathogens, as well as increase the antimicrobial activities of host cells.Overall, the work in this thesis provides information on pneumococcal interactions with the host immune system and highlights the potential use of vesicles in future vaccination strategies.List of scientific papersI. CODEMO M., MUSCHIOL S., IOVINO F., NANNAPANENI P., PLANT L., WAI S. N., HENRIQUES-NORMARK B. Immunomodulatory Effects of Pneumococcal Extracellular Vesicles on Cellular and Humoral Host Defenses. mBio. 2018 Apr 10, 9(2): e00559-18. https://doi.org/10.1128/mBio.00559-18 II. CODEMO M., IOVINO F., MUSCHIOL S., NANNAPANENI P., HENRIQUES-NORMARK B. Streptococcus pneumoniae microparticles evoke a heterologous serotypeindependent protection towards invasive pneumococcal disease. [Manuscript]III. NORMAN M., PATHAK A., CODEMO M., SENDER V., GALLOTTA M., NANNAPANENI P., BOOTSMA H. J., BROWALL S., JONCZYK M., HASTE L., HERMANS P., ANDREW P., HENRIQUES-NORMARK B. Growth and defence strategies affect pneumococcal disease pattern: septicaemia versus pneumonia. [Manuscript]IV. XIE S., SPELMINK L., CODEMO M., SUBRAMANIAN K., PÜTSEP K., HENRIQUES-NORMARK B., OLLIVER M. Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity. PLoS ONE. 2016 Aug 16; 11(8): e0160734. https://doi.org/10.1371/journal.pone.0160734 </p
Trento Urban Transformation. Designing Healthy Cities through. Adaptive Urban Planning
No full textUrban areas constitute key hubs of interventions to drive towards sustainable development: affordable housing, mobility, provision of services, ageing, urban health, social segregation, environmental footprint, and climate action have been shaping urban transformation with unpredictable scenarios. Such challenges require an update of urban planning tools, which need to mirror the complexity of urban patterns and to enhance their capacities to focus on multiple pathways and plurality of goals. The paper presents the research conducted by the Trento Urban Transformation (TUT) research group at the University of Trento as scientific support to the revision of the General Urban Plan of Trento, an alpine city in the north-east of Italy. The research project aims to propose innovative, adaptive, and incremental planning tools to allow flexibility, preparedness to extreme events, and capacity to learn from the past. The proposed city plan draws on a new vision, namely “Trento Leaf Plan”. It defines a strategic vision to cope with urban challenges for a healthier and more resilient habitat. The paper introduces the general approach proposed, and focuses on three tools that have been experimented to shift from a quantitative system based on control to a metabolic, interdisciplinary, and multiscale plan: spatially explicit vegetation and ecosystem services models, the figure of chief resilient officer and integration of environmental criteria in planning tools
Dr. Duane M. Jackson, Morehouse College, July 2011
No full textThis video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer
Predictive factors of vascular intima media thickness in HIV-positive subjects
No full textBackground: The predictive factors of intima media thickness (IMT) in the HIV-infected population are still poorly understood.
Patients and methods: We studied three groups of subjects, aged 30–50 years, to find potential predictive factors of carotid and/or femoral thickening (IMT > 1 mm in at least one area): healthy controls (G1, n = 54), HIV-infected naive (G2, n = 53) and highly active antiretroviral treatment (HAART)-treated subjects (G3, n = 133). All the subjects underwent ultrasonography of the carotid and femoral vessels to evaluate IMT.
Results: Demographic characteristics of the three groups were comparable, except for gender (G1 had a higher percentage of females) and lipid levels (higher in G3). A total of 115 subjects (47.9%) had carotid and/or femoral IMT: 26 in G1 (48.1%), 21 in G2 (39.6%) and 68 in G3 (51.1%). Independent predictive factors of carotid and/or femoral IMT were older age (OR: 2.81, 95% CI: 1.95–4.04, P < 0.01, for each additional 5 years), triglycerides 150 mg/dL (OR: 2.66, 95% CI: 1.27–5.57, P < 0.001), serum glucose 110 mg/dL (OR: 5.24, 95% CI: 1.02–27.05, P = 0.04), high homocysteinaemia (OR: 2.75, 95% CI: 1.17–6.46, P = 0.02) and high body mass index (OR: 1.10, 95% CI: 1–1.22, P = 0.05 for each additional unit); females had a lower risk (OR: 0.38, 95% CI: 0.18–0.79, P < 0.01 versus males). HAART use was not associated with IMT (OR: 0.64, 95% CI: 0.27–1.53, P = 0.32 and OR: 0.80, 95% CI: 0.30–2.13, P = 0.20 for G3 and G2 versus G1, respectively).
Conclusions: This study demonstrates that traditional risk factors for cardiovascular diseases overshadow the role of HAART in determining premature vascular lesion
IL CLAMPAGGIO SOTTODIAFRAMMATICO DELL'AORTA NEL TRATTAMENTO IN ELEZIONE DEGLI ANEURISMI SOTTORENALI DI DIFFICILE CON¬TROLLO
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