20 research outputs found
Admiration, Moral Knowledge and Transformative Experiences
No full textIn this paper, I examine the role played by the emotion of admiration in formulating moral judgments. First, I discuss whether and when admiration is a reliable source of moral knowledge, or, on the contrary, it misleads the subject, leaving her prey to forms of uncritical devotion to unworthy objects of admiration. To do so, I tryto elucidate which underlying theory of emotions best allows one to characterize admiration as a reliable source of moral knowledge. Second, I introduce the notion of transformative moral experience, understood as a subclass of transformative experiences (cf. Paul 2014), and I argue that it is precisely admiration that ensures the rationality of the choices made in such experiences. Finally, in light of this analysis, I show how admiration-together with the constellation of positive and negative emotions connected to the perception of moral exemplarity-acts as a central element for the maintenance of moral integrity. I defend, in particular, the idea that integrity should not be understood as mere coherence, nor as a static maintenance of the moral status quo, but as being firmly rooted in one's own identity yet open to novelty (see Rees and Webber 2014; Cox, La Caze, and Levine 2014, 2017) and especially to the novelty represented by transformative moral experiences
The problems of innovation in the management of science within the university: the special research programs sponsored by the University of Buenos Aires (UBA)
No full textFil: Vaccarezza, Leonardo Silvio. Universidad Nacional de Quilmes. Departamento de Ciencias Sociales; Argentina.En este artículo se presenta una experiencia de gestión de la investigación universitaria orientada en el marco de la definición de políticas institucionales de la organización. Se describe un "instrumento" de gestión relativamente novedoso en el ambiente de la universidad y se señalan algunos efectos y obstáculos que se originan en las particularidades de la organización de la I+D universitarios. Se analiza, por ejemplo, la actuación de estos mecanismos de intervención en la constitución de un campo científico, el rol que juega en estos procesos la morfología del campo y los liderazgos existentes, etc. Entre otras cosas, la experiencia mostró que no basta definir un listado orientativo de áreas temáticas para lograr una efectiva dirección de la investigación.The author discusses the experimental management of a university research program aimed at defining the institutional policies of the organization. He goes onto describe a management “instrument” considered as rather new in the university environment. He also mentions some of the effects and hurdles originating in the distinctive organizational features of university-based research and development activities. Then he analyzes these means of taking part in the creation of a scientific field, the role played ¡n these processes by the morphology of the field and existing leaderships, etc. Among other things, experience has shown that in order to achieve an effective control of the research, it does not suffice to determine a guiding list ,of subjects to be studied
Kinetics of cytokine expression during primary human immunodeficiency virus type 1 infection
No full textIn the present study, we have determined the kinetics of constitutive expression of a panel of cytokines [interleukin (IL) 2, IL-4, IL-6, IL-10, interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha)] in sequential peripheral blood mononuclear cell samples from nine individuals with primary human immunodeficiency virus infection. Expression of IL-2 and IL-4 was barely detected in peripheral blood mononuclear cells. However, substantial levels of IL-2 expression were found in mononuclear cells isolated from lymph node. Expression of IL-6 was detected in only three of nine patients, and IL-6 expression was observed when transition from the acute to the chronic phase had already occurred. Expression of IL-10 and TNF-alpha was consistently observed in all patients tested, and levels of both cytokines were either stable or progressively increased over time. Similar to IL-10 and TNF-alpha, IFN-gamma expression was detected in all patients; however, in five of nine patients, IFN-gamma expression peaked very early during primary infection. The early peak in IFN-gamma expression coincided with oligoclonal expansions of CD8+ T cells in five of six patients, and CD8+ T cells mostly accounted for the expression of this cytokine. These results indicate that high levels of expression of proinflammatory cytokines are associated with primary infection and that the cytokine response during this phase of infection is strongly influenced by oligoclonal expansions of CD8+ T cells
circRNAs as Epigenetic Regulators of Integrity in Blood–Brain Barrier Architecture: Mechanisms and Therapeutic Strategies in Multiple Sclerosis
No full textMultiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease leading to
progressive demyelination and neuronal loss, with extensive neurological symptoms. As one of
the most widespread neurodegenerative disorders, with an age onset of about 30 years, it turns
out to be a socio-health and economic issue, thus necessitating therapeutic interventions currently
unavailable. Loss of integrity in the blood–brain barrier (BBB) is one of the distinct MS hallmarks.
Brain homeostasis is ensured by an endothelial cell-based monolayer at the interface between the
central nervous system (CNS) and systemic bloodstream, acting as a selective barrier. MS results in
enhanced barrier permeability, mainly due to the breakdown of tight (TJs) and adherens junctions
(AJs) between endothelial cells. Specifically, proinflammatory mediator release causes failure in
cytoplasmic exposure of junctions, resulting in compromised BBB integrity that enables blood cells
to cross the barrier, establishing iron deposition and neuronal impairment. Cells with a compromised
cytoskeletal protein network, fiber reorganization, and discontinuous junction structure can
occur, resulting in BBB dysfunction. Recent investigations on spatial transcriptomics have proven
circularRNAs (circRNAs) to be powerful multi-functional molecules able to epigenetically regulate
transcription and structurally support proteins. In the present review, we provide an overview of the
recent role ascribed to circRNAs in maintaining BBB integrity/permeability via cytoskeletal stability.
Increased knowledge of the mechanisms responsible for impairment and circRNA’s role in driving
BBB damage and dysfunction might be helpful for the recognition of novel therapeutic targets to
overcome BBB damage and unrestrained neurodegeneration
The problems of innovation in the management of science within the university: the special research programs sponsored by the University of Buenos Aires (UBA)
No full textEn este artículo se presenta una experiencia de gestión de la investigación universitaria orientada en el marco de la definición de políticas institucionales de la organización. Se describe un "instrumento" de gestión relativamente novedoso en el ambiente de la universidad y se señalan algunos efectos y obstáculos que se originan en las particularidades de la organización de la I+D universitarios. Se analiza, por ejemplo, la actuación de estos mecanismos de intervención en la constitución de un campo científico, el rol que juega en estos procesos la morfología del campo y los liderazgos existentes, etc. Entre otras cosas, la experiencia mostró que no basta definir un listado orientativo de áreas temáticas para lograr una efectiva dirección de la investigación.The author discusses the experimental management of a university research program aimed at defining the institutional policies of the organization. He goes onto describe a management “instrument” considered as rather new in the university environment. He also mentions some of the effects and hurdles originating in the distinctive organizational features of university-based research and development activities. Then he analyzes these means of taking part in the creation of a scientific field, the role played ¡n these processes by the morphology of the field and existing leaderships, etc. Among other things, experience has shown that in order to achieve an effective control of the research, it does not suffice to determine a guiding list ,of subjects to be studied
Sighting acute myocardial infarction through platelet gene expression
No full text© 2019, The Author(s). Acute myocardial infarction is primarily due to coronary atherosclerotic plaque rupture and subsequent thrombus formation. Platelets play a key role in the genesis and progression of both atherosclerosis and thrombosis. Since platelets are anuclear cells that inherit their mRNA from megakaryocyte precursors and maintain it unchanged during their life span, gene expression profiling at the time of an acute myocardial infarction provides information concerning the platelet gene expression preceding the coronary event. In ST-segment elevation myocardial infarction (STEMI), a gene-by-gene analysis of the platelet gene expression identified five differentially expressed genes: FKBP5, S100P, SAMSN1, CLEC4E and S100A12. The logistic regression model used to combine the gene expression in a STEMI vs healthy donors score showed an AUC of 0.95. The same five differentially expressed genes were externally validated using platelet gene expression data from patients with coronary atherosclerosis but without thrombosis. Platelet gene expression profile highlights five genes able to identify STEMI patients and to discriminate them in the background of atherosclerosis. Consequently, early signals of an imminent acute myocardial infarction are likely to be found by platelet gene expression profiling before the infarction occurs
Kinetics of cytokine expression during primary human immunodeficiency virus type 1 (HIV-1) infection.
No full textSurfactant protein D inhibits HIV-1 infection of target cells via interference with gp120-CD4 interaction and modulates pro-inflammatory cytokine production
No full text© 2014 Pandit et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Surfactant Protein SP-D, a member of the collectin family, is a pattern recognition protein, secreted by mucosal epithelial cells and has an important role in innate immunity against various pathogens. In this study, we confirm that native human SP-D and a recombinant fragment of human SP-D (rhSP-D) bind to gp120 of HIV-1 and significantly inhibit viral replication in vitro in a calcium and dose-dependent manner. We show, for the first time, that SP-D and rhSP-D act as potent inhibitors of HIV-1 entry in to target cells and block the interaction between CD4 and gp120 in a dose-dependent manner. The rhSP-D-mediated inhibition of viral replication was examined using three clinical isolates of HIV-1 and three target cells: Jurkat T cells, U937 monocytic cells and PBMCs. HIV-1 induced cytokine storm in the three target cells was significantly suppressed by rhSP-D. Phosphorylation of key kinases p38, Erk1/2 and AKT, which contribute to HIV-1 induced immune activation, was significantly reduced in vitro in the presence of rhSP-D. Notably, anti-HIV-1 activity of rhSP-D was retained in the presence of biological fluids such as cervico-vaginal lavage and seminal plasma. Our study illustrates the multi-faceted role of human SPD against HIV-1 and potential of rhSP-D for immunotherapy to inhibit viral entry and immune activation in acute HIV infection. © 2014 Pandit et al.The work (Project no. 2011-16850) was supported by Medical Innovation Fund of Indian Council of Medical Research, New Delhi, India (www.icmr.nic.in/)
Predisposing Factors and Clinico-Pathological Presentation of Malignant Lesions of the Oro-Facial Region Among Patients Attending the Muhimbili National Hospital in Dar-es-Salaam, Tanzania
No full textThe oro-facial region is made up of a complex anatomical relationship of structures of which may be a source of development of malignant lesions. Often, patients present at the oral and maxillofacial unit of Muhimbili National Hospital with a variety of malignant lesions in the oro-facial region. Majority of these patients are referred cases from upcountry district/regional hospitals and they present with advanced stages of disease with a wide range of complications. Of recent there has been a dramatic change in the characteristics and demography of some of the common malignant lesions of the oro-facial region. Such changes might be attributed to predisposition or systemic changes following exposure to certain external factors.\ud
To determine the predisposing factors and clinico-pathological presentation of malignant lesions of the oro-facial region among patients attending the Muhimbili National Hospital. Cross sectional descriptive hospital based study. Oral and maxillofacial surgery firm, Muhimbili National Hospital. All admitted and outpatients with clinically suspected malignant lesions in the oro-facial region who attended at the Muhimbili National Hospital, Oral surgery department from 1st July 2010 to 31stMarch 2011. Patients were interviewed using a specially designed questionnaire. Clinical examination was done, followed by fine needle aspiration cytology and/or tissue biopsy. A total of 186 patients with cytologically and/or histologically confirmed malignant lesions were included in the study. Data were entered in a computer, cleaned and analyzed using SPSS for windows version 13. A total of 186 patients, 104 (56.0%) males and 82 (44.0%) females with a ratio 1.3:1 were involved in the study. The age at the time of diagnosis ranged from 3 to 83 years with a mean age of 48.4 ± 19.2 SD years. Sixty one (32.8%) patients were aged below 40 years. The commonest observed oral and maxillofacial malignant lesion was Squamous cell carcinoma 96 (51.6%) patients followed by Kaposi’s sarcoma in 17 (9.1%) patients and carcinoma in 10 (5.4%) patients. Tobacco use was reported by 89 (47.8%) patients, of whom 62 (69.6%) patients had used tobacco for more than 20 years while 96 (51.6%) patients reported alcohol use, of whom 49 (51.0%) reported to have used alcohol more than 20 years. Thirty three (17.7%) patients were HIV positive. All patients with Kaposi’s sarcoma were also HIV positive. Malignant eccrine poroma and polymorphous low grade adenocarcinoma are rare tumours in the maxillofacial region that were encountered. Squamous cell carcinoma was the most common malignant tumour in the oral and maxillofacial region. Use of tobacco and/or alcohol was the predisposing factors for squamous cell carcinoma. There was an increased frequency of malignant tumours in the oral and maxillofacial region among young patients. Patients presented rather late with advanced tumours that many times could only be managed by palliative therapy. All patients with Kaposi’s sarcoma were HIV positive.\u
