Pain and Pleasure in Plato's Physiology

We trace the development of Plato’s physiology of pleasure and pain from a rudimentary account in the "Gorgias" to a sophisticated account in the "Philebus". In the earlier account Plato treats pains as lacks and pleasures as replenishments. In the later account he treats pleasures and pains as in part object directed mental states. In particular, he treats pains as perceptions of disintegrated states which lack determinate being. We argue that Plato’s later account constitutes a considerable advance on previous theories of pain and on his own earlier theory. However, we point out that modern research has shown that Plato is wrong to identify pains with perceptions of disintegrated states. Nevertheless, we suggest that had Plato known about the results of modern research, he would have been able to say that pains are perceptions of threats of disintegration into the indeterminate

Plato on False Pains and False Pleasures

A commonsense view about pains and pleasures is that they are mere sensations. Perceiving pains as painful and pleasures as pleasant does not involve beliefs about the world. Plato argues for the bizarre claim that what makes pleasures pleasant and pains painful are beliefs

Area law for fixed points of rapidly mixing dissipative quantum systems

We prove an area law with a logarithmic correction for the mutual information for fixed points of local dissipative quantum system satisfying a rapid mixing condition, under either of the following assumptions: the fixed point is pure, or the system is frustration free.Comment: 17 pages, 1 figure. Final versio

IBA57 recruits ISCA2 to form a [2Fe-2S] cluster-mediated complex

The maturation of mitochondrial iron-sulfur proteins requires a complex protein machinery. Human IBA57 protein was proposed to act in a late phase of this machinery, along with GLRX5, ISCA1, and ISCA2. However, a molecular picture on how these proteins cooperate is not defined yet. We show here that IBA57 forms a heterodimeric complex with ISCA2 by bridging a [2Fe-2S] cluster, that [2Fe-2S] cluster binding is absolutely required to promote the complex formation, and that the cysteine of the conserved motif characterizing IBA57 protein family and the three conserved cysteines of the ISCA protein family act as cluster ligands. The [2Fe-2S] heterodimeric complex is the final product when IBA57 is either exposed to [2Fe-2S] ISCA2 or in the presence of [2Fe-2S] GLRX5 and apo ISCA2. We also find that the [2Fe-2S] ISCA2-IBA57 complex is resistant to highly oxidative environments and is capable of reactivating apo aconitase in vitro. Collectively, our data delinate a [2Fe-2S] cluster transfer pathway involving three partner proteins of the mitochondrial ISC machinery, that is, GLRX5, ISCA2 and IBA57, which leads to the formation of a [2Fe-2S] ISCA2-IBA57 complex

Objective Quantification of Neuromotor Symptoms in Parkinson's Disease: Implementation of a Portable, Computerized Measurement Tool

Quantification of neuromotor symptoms with device-based measures provides a useful supplement to clinical evaluation. Research using the CATSYS has established its utility as a computerized measurement system to quantify neuromotor function. The primary objective of this study is to provide technical guidance on the use of the CATSYS in Parkinson's disease (PD). Forty-four patients with idiopathic PD and 28 healthy controls were prospectively recruited and evaluated with CATSYS, a portable, Windows-based system consisting of a data logger and four different sensors (tremor pen, touch recording plate, reaction time handle, and force plate for balance recording) for quantification of neuromotor functions. CATSYS discriminated between PD and controls on measurements of rest/postural tremor, pronation/supination, finger tapping, simple reaction time, and postural sway intensity and velocity. CATSYS measurements using the proposed test battery were associated with relevant clinician-rated Unified Parkinson's disease rating scale (UPDRS) items assessing tremor and bradykinesia. More work is warranted to establish CATSYS as a diagnostic/monitoring instrument in movement disorders using the proposed technical approaches

Immune function and dysfunction are determined by lymphoid tissue efficacy

Lymphoid tissue returns to a steady state once each immune response is resolved, and although this occurs multiple times throughout life, its structural integrity and functionality remain unaffected. Stromal cells orchestrate cellular interactions within lymphoid tissue, and any changes to the microenvironment can have detrimental outcomes and drive disease. A breakdown in lymphoid tissue homeostasis can lead to a loss of tissue structure and function that can cause aberrant immune responses. This Review highlights recent advances in our understanding of lymphoid tissue function and remodelling in adaptive immunity and in disease states. We discuss the functional role of lymphoid tissue in disease progression and explore the changes to lymphoid tissue structure and function driven by infection, chronic inflammatory conditions and cancer. Understanding the role of lymphoid tissues in immune responses to a wide range of pathologies allows us to take a fuller systemic view of disease progression

Platelet endothelial cell adhesion molecule-1 regulates collagen-stimulated platelet function by modulating the association of phosphatidylinositol 3-kinase with Grb-2-associated binding protein-1 and linker for activation of T cells

Background: Platelet activation by collagen depends on signals transduced by the glycoprotein (GP)VI–Fc receptor (FcR)-chain collagen receptor complex, which involves recruitment of phosphatidylinositol 3-kinase (PI3K) to phosphorylated tyrosines in the linker for activation of T cells (LAT). An interaction between the p85 regulatory subunit of PI3K and the scaffolding molecule Grb-2-associated binding protein-1 (Gab1), which is regulated by binding of the Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) to Gab1, has been shown in other cell types to sustain PI3K activity to elicit cellular responses. Platelet endothelial cell adhesion molecule-1 (PECAM-1) functions as a negative regulator of platelet reactivity and thrombosis, at least in part by inhibiting GPVI–FcR-chain signaling via recruitment of SHP-2 to phosphorylated immunoreceptor tyrosine-based inhibitory motifs in PECAM-1. Objective: To investigate the possibility that PECAM-1 regulates the formation of the Gab1–p85 signaling complexes, and the potential effect of such interactions on GPVI-mediated platelet activation in platelets. Methods: The ability of PECAM-1 signaling to modulate the LAT signalosome was investigated with immunoblotting assays on human platelets and knockout mouse platelets. Results: PECAM-1-associated SHP-2 in collagen-stimulated platelets binds to p85, which results in diminished levels of association with both Gab1 and LAT and reduced collagen-stimulated PI3K signaling. We therefore propose that PECAM-1-mediated inhibition of GPVI-dependent platelet responses result, at least in part, from recruitment of SHP-2–p85 complexes to tyrosine-phosphorylated PECAM-1, which diminishes the association of PI3K with activatory signaling molecules, such as Gab1 and LAT

Assessing cell migration in hydrogels: An overview of relevant materials and methods

Cell migration is essential in numerous living processes, including embryonic development, wound healing, immune responses, and cancer metastasis. From individual cells to collectively migrating epithelial sheets, the locomotion of cells is tightly regulated by multiple structural, chemical, and biological factors. However, the high complexity of this process limits the understanding of the influence of each factor. Recent advances in materials science, tissue engineering, and microtechnology have expanded the toolbox and allowed the development of biomimetic in vitro assays to investigate the mechanisms of cell migration. Particularly, three-dimensional (3D) hydrogels have demonstrated a superior ability to mimic the extracellular environment. They are therefore well suited to studying cell migration in a physiologically relevant and more straightforward manner than in vivo approaches. A myriad of synthetic and naturally derived hydrogels with heterogeneous characteristics and functional properties have been reported. The extensive portfolio of available hydrogels with different mechanical and biological properties can trigger distinct biological responses in cells affecting their locomotion dynamics in 3D. Herein, we describe the most relevant hydrogels and their associated physico-chemical characteristics typically employed to study cell migration, including established cell migration assays and tracking methods. We aim to give the reader insight into existing literature and practical details necessary for performing cell migration studies in 3D environments.publishedVersio