The Coexistence of Contradictory Properties in the Same Subject According to Aristotle

In Metaphysics, Book Gamma, Aristotle argues that he who asserts a contradiction is committed to a rejection of degrees. On the other hand, though, Aristotle claims that there can be no intermediary situation in-between pure or entire truth or existence and utter, complete falseness or nonexistence. Such a combination of views can be rendered noncontradictory at best through objectionable manoeuvres. Although Aristotle accepts that two contrary properties can be both present in the same object to some extent, he is, in order to keep clear of contradictions, bound to regard intermediary situations as something irreducibly different from both extremes.Peer reviewe

Struktur- und Funktionsuntersuchungen am humanen Interleukin-11-Rezeptorkomplex

Interleukin-11 (IL-11) belongs to the interleukin-6 (IL-6)-type subfamily of long-chain helical cytokines, which all share the glycoprotein gp130 as a signal transducing receptor component. IL-11 acts on cells expressing gp130 and the IL-11 receptor (IL-11R) alpha-subunit (IL-11R-alpha). The third extracellular, membran proximal domain of the IL-11R-alpha is able to bind with high affinity to IL-11. Using a three-dimensional model of human IL-11, surface exposed amino acid residues of IL-11 were selected for mutagenesis using analogies to the well-characterized receptor recruitment sites of IL-6, CNTF, and LIF. The respective mutants of human IL-11 were expressed as soluble fusion proteins in bacteria and their biological activities were determined. Several mutants with substantially decreased bioactivity were identified and further analyzed in regard to recruitment of IL-11R-alpha and gp130. The structural epitopes of IL-11 required for the recruitment of the individual receptor subunits (sites 1, 2 and 3) have been defined. By plasmon resonance experiments, it was shown that the antagonistic monoclonal antibodies against IL-11 (H2, H56 and E33) bind to amino acids located at site 2. The study an description of the mutant H182L, which engages IL-11R-alpha more efficiently, offer considerable perspectives for the rational design of IL-11 antagonists and hyperagonists. Furthermore, it was shown that the third extracellular domain of the IL-11R-aplha is able to form a ternary complex with IL-11 and gp130 and that it does not require the presence of the cytokine to bind to one molecule gp130. In the third part, no cleavage of the IL-11R-alpha could be detected on macrophages whereas the shedding of the IL-6 receptor alpha-subunit could be induced with LPS and PMA

Struktur- und Funktionsuntersuchungen am humanen Interleukin-11-Rezeptorkomplex

Interleukin-11 (IL-11) belongs to the interleukin-6 (IL-6)-type subfamily of long-chain helical cytokines, which all share the glycoprotein gp130 as a signal transducing receptor component. IL-11 acts on cells expressing gp130 and the IL-11 receptor (IL-11R) alpha-subunit (IL-11R-alpha). The third extracellular, membran proximal domain of the IL-11R-alpha is able to bind with high affinity to IL-11. Using a three-dimensional model of human IL-11, surface exposed amino acid residues of IL-11 were selected for mutagenesis using analogies to the well-characterized receptor recruitment sites of IL-6, CNTF, and LIF. The respective mutants of human IL-11 were expressed as soluble fusion proteins in bacteria and their biological activities were determined. Several mutants with substantially decreased bioactivity were identified and further analyzed in regard to recruitment of IL-11R-alpha and gp130. The structural epitopes of IL-11 required for the recruitment of the individual receptor subunits (sites 1, 2 and 3) have been defined. By plasmon resonance experiments, it was shown that the antagonistic monoclonal antibodies against IL-11 (H2, H56 and E33) bind to amino acids located at site 2. The study an description of the mutant H182L, which engages IL-11R-alpha more efficiently, offer considerable perspectives for the rational design of IL-11 antagonists and hyperagonists. Furthermore, it was shown that the third extracellular domain of the IL-11R-aplha is able to form a ternary complex with IL-11 and gp130 and that it does not require the presence of the cytokine to bind to one molecule gp130. In the third part, no cleavage of the IL-11R-alpha could be detected on macrophages whereas the shedding of the IL-6 receptor alpha-subunit could be induced with LPS and PMA

Importance of the membrane-proximal extracellular domains for activation of the signal transducer glycoprotein 130

O objetivo do estudo foi avaliar a prevalência de diabetes auto-referido em idosos, identificando fatores associados, conhecimento e práticas quanto às opções de tratamento. Trata-se de estudo transversal de base populacional, com amostra estratificada por conglomerados e em dois estágios, em municípios do Estado de São Paulo, Brasil. Dos 1.949 idosos, 15,4% referiram diabetes. O índice de massa corporal e a prática de exercício físico estiveram associados à doença. Houve diferença entre diabéticos e não diabéticos quanto à auto-avaliação da saúde, internação, morbidade auto-referida nos últimos 15 dias, e relato das seguintes doenças: hipertensão, anemia, doença renal e cardiovascular. Não houve desigualdade em relação à renda familiar per capita quanto à visita ao médico/serviço de saúde, à participação em grupos de discussão e às práticas de controle da doença. O estudo sugere a importância de mudanças comportamentais, como estratégias de prevenção e controle da doença e suas complicações, bem como a necessidade de oferta de intervenções educativas com ampliação da cobertura de cuidados aos diabéticos.The aim of the study was to assess the prevalence of self-reported diabetes in the elderly, identifying associated factors, knowledge, and practices related to treatment options. This was a cross-sectional population-based study with stratified clustered two-stage sampling in six municipalities in the State of São Paulo, Brazil. Among the 1,949 elderly, 15.4% presented self-reported diabetes. Body mass index and exercising were statistically associated with diabetes. There was a significant difference between diabetics and non-diabetics in terms of self-rated health, hospitalization, self-reported illness in the previous two weeks, and report of the following diseases: hypertension, anemia, chronic kidney disease, and heart disease. In terms of per capita family income, there was no difference in regular medical visits, participation in discussion groups, and control practices. The findings show the need for behavior changes to prevent and control diabetes and its complications. Educational interventions are needed to expand the coverage of diabetes care

Tracking Targeted Bimodal Nanovaccines: Immune Responses and Routing in Cells, Tissue, and Whole Organism

Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs), involved in the induction of immunity and currently exploited for antitumor immunotherapies. An optimized noninvasive imaging modality capable of determining and quantifying DC-targeted nanoparticle (NP) trajectories could provide valuable information regarding therapeutic vaccine outcome. Here, targeted poly­(d,l-lactide-<i>co</i>-glycolide) nanoparticles (PLGA NPs) recognizing DC receptors were equipped with superparamagnetic iron oxide particles (SPIO) or gold nanoparticles with fluorescently labeled antigen. The fluorescent label allowed for rapid analysis and quantification of DC-specific uptake of targeted PLGA NPs in comparison to uptake by other cells. Transmission electron microscopy (TEM) showed that a fraction of the encapsulated antigen reached the lysosomal compartment of DCs, where SPIO and gold were already partially released. However, part of the PLGA NPs localized within the cytoplasm, as confirmed by confocal microscopy. DCs targeted with NPs carrying SPIO or fluorescent antigen were detected within lymph nodes as early as 1 h after injection by magnetic resonance imaging (MRI). Despite the fact that targeting did not markedly affect PLGA NP biodistribution on organism and tissue level, it increased delivery of NPs to DCs residing in peripheral lymph nodes and resulted in enhanced T cell proliferation. In conclusion, two imaging agents within a single carrier allows tracking of targeted PLGA NPs at the subcellular, cellular, and organismal levels, thereby facilitating the rational design of in vivo targeted vaccination strategies