526 research outputs found
Reliability and reproducibility of Atlas information
We discuss the reliability and reproducibility of much of the information
contained in the Atlas of Finite Groups
Targeted subendothelial matrix oxidation by myeloperoxidase triggers myosin II-dependent de-adhesion and alters signaling in endothelial cells
During inflammation, myeloperoxidase (MPO) released by circulating leukocytes accumulates within the subendothelial matrix by binding to and transcytosing the endothelium. Oxidative reactions catalyzed by subendothelial-localized MPO are implicated as a key cause of endothelial dysfunction in inflammatory vascular diseases. Whilst the subendothelial matrix is a reactive target for MPO-derived oxidants in disease, the functional implications of oxidative matrix modification for the endothelium are largely unknown. Here we show that hypochlorous acid (HOCl) produced by endothelial-transcytosed MPO oxidizes the subendothelial matrix, involving covalent crosslinking of the adhesive matrix protein fibronectin. Real-time biosensor and live cell imaging studies showed that HOCl-mediated matrix oxidation triggers rapid membrane retraction from the substratum and adjacent cells (de-adhesion). This de-adhesion was linked with the alteration of Tyr-118 phosphorylation of paxillin, a key focal adhesion-dependent signaling process, as well as Rho kinase-dependent myosin light chain-2 phosphorylation. De-adhesion dynamics were dependent on the contractile state of cells, with myosin II inhibition with blebbistatin markedly attenuating the rate of membrane retraction. Rho kinase inhibition with Y-27632 also conferred protection, but not during the initial phase of membrane retraction, which was driven by pre-existing actomyosin tensile stress. Notably, diversion of MPO from HOCl production by thiocyanate and nitrite attenuated de-adhesion and associated signaling responses, despite the latter substrate supporting MPO-catalyzed fibronectin nitration. This study indicates that HOCl-mediated matrix oxidation by subendothelial MPO deposits may play an important and previously unrecognized role in altering endothelial adhesion, signaling and integrity during inflammatory vascular disorders
The Ontology of Intentional Agency in Light of Neurobiological Determinism: Philosophy Meets Folk Psychology
The moot point of the Western philosophical rhetoric about free will
consists in examining whether the claim of authorship to intentional, deliberative
actions fits into or is undermined by a one-way causal framework of determinism.
Philosophers who think that reconciliation between the two is possible are known as
metaphysical compatibilists. However, there are philosophers populating the other
end of the spectrum, known as the metaphysical libertarians, who maintain that claim
to intentional agency cannot be sustained unless it is assumed that indeterministic
causal processes pervade the action-implementation apparatus employed by the agent.
The metaphysical libertarians differ among themselves on the question of whether the
indeterministic causal relation exists between the series of intentional states and
processes, both conscious and unconscious, and the action, making claim for what has
come to be known as the event-causal view, or between the agent and the action,
arguing that a sort of agent causation is at work. In this paper, I have tried to propose
that certain features of both event-causal and agent-causal libertarian views need to be
combined in order to provide a more defendable compatibilist account accommodating
deliberative actions with deterministic causation. The ‘‘agent-executed-eventcausal
libertarianism’’, the account of agency I have tried to develop here, integrates
certain plausible features of the two competing accounts of libertarianism turning
them into a consistent whole. I hope to show in the process that the integration of these
two variants of libertarianism does not challenge what some accounts of metaphysical
compatibilism propose—that there exists a broader deterministic relation between the
web of mental and extra-mental components constituting the agent’s dispositional
system—the agent’s beliefs, desires, short-term and long-term goals based on them,
the acquired social, cultural and religious beliefs, the general and immediate and
situational environment in which the agent is placed, etc. on the one hand and the
decisions she makes over her lifetime on the basis of these factors. While in the
‘‘Introduction’’ the philosophically assumed anomaly between deterministic causation
and the intentional act of deciding has been briefly surveyed, the second section is
devoted to the task of bridging the gap between compatibilism and libertarianism. The
next section of the paper turns to an analysis of folk-psychological concepts and
intuitions about the effects of neurochemical processes and prior mental events on the
freedom of making choices. How philosophical insights can be beneficially informed
by taking into consideration folk-psychological intuitions has also been discussed,
thus setting up the background for such analysis. It has been suggested in the end that
support for the proposed theory of intentional agency can be found in the folk-psychological intuitions, when they are taken in the right perspective
Nuclear factor κB-inducing kinase activation as a mechanism of pancreatic β cell failure in obesity
The nuclear factor κB (NF-κB) pathway is a master regulator of inflammatory processes and is implicated in insulin resistance and pancreatic β cell dysfunction in the metabolic syndrome. Whereas canonical NF-κB signaling is well studied, there is little information on the divergent noncanonical NF-κB pathway in the context of pancreatic islet dysfunction. Here, we demonstrate that pharmacological activation of the noncanonical NF-κB-inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo. We identify NIK as a critical negative regulator of β cell function, as pharmacological NIK activation results in impaired glucose-stimulated insulin secretion in mouse and human islets. NIK levels are elevated in pancreatic islets isolated from diet-induced obese (DIO) mice, which exhibit increased processing of noncanonical NF-κB components p100 to p52, and accumulation of RelB. TNF and receptor activator of NF-κB ligand (RANKL), two ligands associated with diabetes, induce NIK in islets. Mice with constitutive β cell-intrinsic NIK activation present impaired insulin secretion with DIO. NIK activation triggers the noncanonical NF-κB transcriptional network to induce genes identified in human type 2 diabetes genome-wide association studies linked to β cell failure. These studies reveal that NIK contributes a central mechanism for β cell failure in diet-induced obesity
Serum Amyloid A, C-Reactive Protein, and Retinal Microvascular Changes in Hypertensive Diabetic and Nondiabetic Individuals: An Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) substudy
To study the association of the inflammatory markers serum amyloid A (SAA) and C-reactive protein (CRP) with retinal microvascular parameters in hypertensive individuals with and without type 2 diabetes
Mind Perception Is the Essence of Morality
Mind perception entails ascribing mental capacities to other entities, whereas moral judgment entails labeling entities as good or bad or actions as right or wrong. We suggest that mind perception is the essence of moral judgment. In particular, we suggest that moral judgment is rooted in a cognitive template of two perceived minds—a moral dyad of an intentional agent and a suffering moral patient. Diverse lines of research support dyadic morality. First, perceptions of mind are linked to moral judgments: dimensions of mind perception (agency and experience) map onto moral types (agents and patients), and deficits of mind perception correspond to difficulties with moral judgment. Second, not only are moral judgments sensitive to perceived agency and experience, but all moral transgressions are fundamentally understood as agency plus experienced suffering—that is, interpersonal harm—even ostensibly harmless acts such as purity violations. Third, dyadic morality uniquely accounts for the phenomena of dyadic completion (seeing agents in response to patients, and vice versa), and moral typecasting (characterizing others as either moral agents or moral patients). Discussion also explores how mind perception can unify morality across explanatory levels, how a dyadic template of morality may be developmentally acquired, and future directions
Characterization of global fields by Dirichlet L-series
We prove that two global fields are isomorphic if and only if there is an isomorphism of groups of Dirichlet characters that preserves L-series
Angiotensin II receptor expression and relation to Helicobacter pylori-infection in the stomach of the Mongolian gerbil
<p>Abstract</p> <p>Background</p> <p>The role of the renin-angiotensin system in gastric physiology and disease has as yet been sparsely explored. The first aim of the study was to investigate the baseline presence and location of angiotensin II receptors (AT1R and AT2R) in the stomach of the Mongolian gerbil. A second aim was to elucidate whether the presence of <it>H. pylori </it>infection is associated with changes in the expression of these receptors.</p> <p>Methods</p> <p><it>H. pylori</it>-negative and <it>H. pylori-</it>infected (strain SS1 or TN2GF4) male Mongolian gerbils were investigated. The stomachs were examined at six or 12 months after inoculation by the use of immunohistochemistry, western blot and microscopic morphometry.</p> <p>Results</p> <p>AT1R and AT2R were located in a variety of cells in the gerbil gastric wall, including a subpopulation of endocrine cells in the antral mucosa and inflammatory cells infiltrating <it>H. pylori</it>-infected stomachs. Gerbils infected with the SS1 strain showed a significantly increased antral AT1R protein expression and an increased number of infiltrating polymorphonuclear leucocytes (PMNs) at 12 months. The AT1R protein expression correlated with the number of PMNs and the antral expression of myeloperoxidase.</p> <p>Conclusions</p> <p>Angiotensin II receptors are present in a variety of cells in the gastric wall of the Mongolian gerbil. The results indicate an influence dependent on the <it>H. pylori </it>strain on the gastric AT1R expression and a relationship between gastric AT1R expression and mucosal PMNs infiltration.</p
Serum amyloid A (SAA): a novel biomarker for uterine serous papillary cancer
BACKGROUND: Uterine serous papillary carcinoma (USPC) is a biologically aggressive variant of endometrial cancer. We investigated
the expression of Serum Amyloid A (SAA) and evaluated its potential as a serum biomarker in USPC patients.
METHODS: SAA gene and protein expression levels were evaluated in USPC and normal endometrial tissues (NEC) by real-time PCR,
immunohistochemistry (IHC), flow cytometry and by a sensitive bead-based immunoassay. SAA concentration in 123 serum samples
from 51 healthy women, 42 women with benign diseases, and 30 USPC patients were also studied.
RESULTS: SAA gene expression levels were significantly higher in USPC when compared with NEC (mean copy number by
RT\u2013PCR\ubc162 vs 2.21; P\ubc0.0002). IHC revealed diffuse cytoplasmic SAA protein staining in USPC tissues. High intracellular levels
of SAA were identified in primary USPC cell lines evaluated by flow cytometry and SAA was found to be actively secreted in vitro.
SAA concentrations (mgml 1) had a median (95% CIs) of 6.0 (4.0\u20138.9) in normal healthy females and 6.0 (4.2\u20138.1) in patients with
benign disease (P\ubc0.92). In contrast, SAA values in the serum of USPC patients had a median (95% CI) of 15.6 (9.2\u201356.2),
significantly higher than those in the healthy group (P\ubc0.0005) and benign group (P\ubc0.0006). Receiver operating characteristics
(ROC) analysis of serum SAA to classify advanced- and early-stage USPC yielded an area under the ROC curve of 0.837
(P\ubc0.0024).
CONCLUSION: SAA is not only a liver-secreted protein but is also a USPC cell product. SAA may represent a novel biomarker for
USPC to assist in staging patients preoperatively, and to monitor early-disease recurrence and response to therapy
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