Shifting Attention From Theory to Practice in Philosophy of Biology

Traditional approaches in philosophy of biology focus attention on biological concepts, explanations, and theories, on evidential support and inter-theoretical relations. Newer approaches shift attention from concepts to conceptual practices, from theories to practices of theorizing, and from theoretical reduction to reductive retooling. In this article, I describe the shift from theory-focused to practice-centered philosophy of science and explain how it is leading philosophers to abandon fundamentalist assumptions associated with traditional approaches in philosophy of science and to embrace scientific pluralism. This article comes in three parts, each illustrating the shift from theory-focused to practice-centered epistemology. The first illustration shows how shifting philosophical attention to conceptual practice reveals how molecular biologists succeed in identifying coherent causal strands within systems of bewildering complexity. The second illustration suggests that analyzing how a multiplicity of alternative models function in practice provides an illuminating approach for understanding the nature of theoretical knowledge in evolutionary biology. The third illustration demonstrates how framing reductionism in terms of the reductive retooling of practice offers an informative perspective for understanding why putting DNA at the center of biological research has been incredibly productive throughout much of biology. Each illustration begins by describing how traditional theory-focused philosophical approaches are laden with fundamentalist assumptions and then proceeds to show that shifting attention to practice undermines these assumptions and motivates a philosophy of scientific pluralism

Application of the PM6 semi-empirical method to modeling proteins enhances docking accuracy of AutoDock

<p>Abstract</p> <p>Background</p> <p>Molecular docking methods are commonly used for predicting binding modes and energies of ligands to proteins. For accurate complex geometry and binding energy estimation, an appropriate method for calculating partial charges is essential. AutoDockTools software, the interface for preparing input files for one of the most widely used docking programs AutoDock 4, utilizes the Gasteiger partial charge calculation method for both protein and ligand charge calculation. However, it has already been shown that more accurate partial charge calculation - and as a consequence, more accurate docking- can be achieved by using quantum chemical methods. For docking calculations quantum chemical partial charge calculation as a routine was only used for ligands so far. The newly developed Mozyme function of MOPAC2009 allows fast partial charge calculation of proteins by quantum mechanical semi-empirical methods. Thus, in the current study, the effect of semi-empirical quantum-mechanical partial charge calculation on docking accuracy could be investigated.</p> <p>Results</p> <p>The docking accuracy of AutoDock 4 using the original AutoDock scoring function was investigated on a set of 53 protein ligand complexes using Gasteiger and PM6 partial charge calculation methods. This has enabled us to compare the effect of the partial charge calculation method on docking accuracy utilizing AutoDock 4 software. Our results showed that the docking accuracy in regard to complex geometry (docking result defined as accurate when the RMSD of the first rank docking result complex is within 2 Å of the experimentally determined X-ray structure) significantly increased when partial charges of the ligands and proteins were calculated with the semi-empirical PM6 method.</p> <p>Out of the 53 complexes analyzed in the course of our study, the geometry of 42 complexes were accurately calculated using PM6 partial charges, while the use of Gasteiger charges resulted in only 28 accurate geometries. The binding affinity estimation was not influenced by the partial charge calculation method - for more accurate binding affinity prediction development of a new scoring function for AutoDock is needed.</p> <p>Conclusion</p> <p>Our results demonstrate that the accuracy of determination of complex geometry using AutoDock 4 for docking calculation greatly increases with the use of quantum chemical partial charge calculation on both the ligands and proteins.</p

Asymptomatic Cardiomyopathy in Children and Adolescents with Type 1 Diabetes Mellitus: Association of Echocardiography Indicators with Duration of Diabetes Mellitus and Metabolic Parameters

This study was designed to determine the relationship of dimensions, wall thickness and function of the left ventricle with diabetes duration, fasting blood glucose, lipid profile, beta-OH-butyrate, free fatty acids (FFA) and carnitine levels in children and adolescents with type 1 diabetes mellitus (DM1) who had no cardiovascular complications. Thirty-five patients with DM1. (18 F/17 M, mean age: 12.0 years) and age matched control children (n = 24) were enrolled in the study. Patients with DM1 were subdivided into Group I (mean DM1 duration 3.5 years, n = 14), and Group II (mean DM1 duration 8.2 years, n = 21). Dimensions, wall thickness and systolic functions of the left ventricle were normal in all patients with DM1. Diastolic functions were normal in Group I. In Group II, peak A wave velocity (AVEL) (p = 0.004), velocity-time integral of A wave (AVTI) (p = 0.007) and isovolumetric relaxation time corrected by heart rate (cIVRT) (p = 0.048) were high, and peak E wave velocity (EVEL) and velocity-time integral of E wave (EVTI) were normal. E/A (p < 0.0001) and EVTI/AVTI (p = 0.001) were low in this group. In Group 1, systolic and diastolic blood pressure, HDL-cholesterol and FFA values were normal; total cholesterol (p = 0.047), LDL-cholesterol (p = 0.017), beta-OH-butyrate (p = 0.003), and acetyl carnitine (p = 0.006) levels were high. In Group 11, diastolic blood pressure (p = 0.008), total cholesterol (p < 0.0001) and LDL-cholesterol (p < 0.0001) were increased; and total carnitine (p = 0.019), free carnitine (p = 0.002) and HDL-cholesterol (p = 0.039) were decreased. Correlations were detected between total carnitine and AVEL and HR; free carnitine and AVEL, E/A and HR; HbA(1c) and EVTI/AVTI and cIVRT; LDL-cholesterol and E/A, EVTI/AVTI ratios and cIVRT; HDL-cholesterol and AVEL; FFA and LVDD, IVSD, LVPWD, LVmass and CO; metabolic parameters and DM1 duration and echocardiographic findings such as AVEL, EVEL, EVTI, VmaxAV and CO. In conclusion, left ventricular dimensions, wall thickness and systolic functions were normal in children and adolescents with DM1 who had no obvious cardiovascular complications. Left ventricular diastolic functions were abnormal in patients of Group II. Left ventricular diastolic function abnormalities were associated with glycemic control, free and total carnitine, and LDL- and HDL-cholesterol levels

Neurotrophic keratitis

Neurotrophic keratopathy is a degenerative corneal disease induced by an impairment of trigeminal nerve. Impairment of loss of corneal sensory innervation is responsible for corneal epithelial defects, ulcer, and perforation. In the present report, we reviewed the pathogenesis, diagnosis, and therapeutic aspects of this disease. An accurate history and clinical examination, including the function of cranial nerves, together with the clinical features of the ocular surface are essential for a prompt diagnosis. The evaluation of the corneal sensitivity and tear film function are important diagnostic steps as well. Specific medical and surgical treatments, based on the clinical staging of the disease, are often able to halt its progression. Future developments in the medical treatment including the administration of neuropeptide and growth factors are presented