Structure, expression, and function of kynurenine aminotransferases in human and rodent brains

Kynurenine aminotransferases (KATs) catalyze the synthesis of kynurenic acid (KYNA), an endogenous antagonist of N-methyl-d-aspartate and alpha 7-nicotinic acetylcholine receptors. Abnormal KYNA levels in human brains are implicated in the pathophysiology of schizophrenia, Alzheimer’s disease, and other neurological disorders. Four KATs have been reported in mammalian brains, KAT I/glutamine transaminase K/cysteine conjugate beta-lyase 1, KAT II/aminoadipate aminotransferase, KAT III/cysteine conjugate beta-lyase 2, and KAT IV/glutamic-oxaloacetic transaminase 2/mitochondrial aspartate aminotransferase. KAT II has a striking tertiary structure in N-terminal part and forms a new subgroup in fold type I aminotransferases, which has been classified as subgroup Iε. Knowledge regarding KATs is vast and complex; therefore, this review is focused on recent important progress of their gene characterization, physiological and biochemical function, and structural properties. The biochemical differences of four KATs, specific enzyme activity assays, and the structural insights into the mechanism of catalysis and inhibition of these enzymes are discussed.     

Effect of latent iron deficiency on the levels of iron, calcium, zinc, copper, manganese, cadmium and lead in liver, kidney and spleen of growing rats

Feeding a marginally low iron content diet (18-20 mg iron/kg diet) to weaned (21-day-old) rats for 8 weeks produced a significant decrease in liver non-heme iron (66%, p less than 0.001) but no change in blood hemoglobin. Total iron contents of liver (56%, p less than 0.01), spleen (20%, p less than 0.05), and kidney (19%, p less than 0.05) were also found to decrease along with increased zinc, copper, calcium, manganese lead and cadmium in various organs. The magnitude of alteration of a metal was different in different organs. However, liver was found to be the most affected organ. Two weeks of rehabilitation with iron-sufficient diet (390 mg iron/kg diet) normalized these altered levels.     

Effect of latent iron deficiency on the levels of iron,calcium, zinc,copper, manganese,cadmium and lead in liver,kidney and spleen of growing rats

Summary Feeding a marginally low iron content diet (18–20 mg iron/kg diet) to weaned (21-day-old) rats for 8 weeks produced a significant decrease in liver non-heme iron (66%, p<0.001) but no change in blood hemoglobin. Total iron contents of liver (56%, p<0.01), spleen (20%, p<0.05), and kidney (19%, p<0.05) were also found to decrease along with increased zinc, copper, calcium, manganese lead and cadmium in various organs. The magnitude of alteration of a metal was different in different organs. However, liver was found to be the most affected organ. Two weeks of rehabilitation with iron-sufficient diet (390 mg iron/kg diet) normalized these altered levels.     

Unification, explanation, and the composition of causes in Newtonian mechanics

William Whewell's philosophy of scientific discovery is applied to the problem of understanding the nature of unification and explanation by the composition of causes in Newtonian mechanics. The essay attempts to demonstrate: (1) the sense in which ‘approximate’ laws (e.g. Kepler's laws of planetary motion) successfully refer to real physical systems rather than to (fictitious) idealizations of them; (2) why good theoretical constructs are not badly underdetermined by observation; and why, in particular, Newtonian forces are not conventional and (3) how empiricist arguments against the existence of component causes, and against the veracity of the fundamental laws, are flawed.     

Circularity,indispensability, and mathematical explanation in science

In this paper I consider the objection that the Enhanced Indispensability Argument (EIA) is circular and hence fails to support mathematical platonism. The objection is that the explanandum in any mathematical explanation of a physical phenomenon is itself identified using mathematical concepts. Hence the explanandum is only genuine if the truth of some mathematical theory is already presupposed. I argue that this objection deserves to be taken seriously, that it does sometimes undermine support for EIA, but that there is no reason to think that circularity is an unavoidable feature of mathematical explanation in science.     

Prediction,diagnosis, and causal thinking in forecasting

While forecasting involves forward/predictive thinking, it depends crucially on prior diagnosis for suggesting a model of the phenomenon, for defining‘relevant’variables, and for evaluating forecast accuracy via the model. The nature of diagnostic thinking is examined with respect to these activities. We first consider the difficulties of evaluating forecast accuracy without a causal model of what generates outcomes. We then discuss the development of models by considering how attention is directed to variables via analogy and metaphor as well as by what is unusual or abnormal. The causal relevance of variables is then assessed by reference to probabilistic signs called‘cues to causality’. These are: temporal order, constant conjunction, contiguity in time and space, number of alternative explanations, similarity, predictive validity, and robustness. The probabilistic nature of the cues is emphasized by discussing the concept of spurious correlation and how causation does not necessarily imply correlation. Implications for improving forecasting are considered with respect to the above issues.     

MICALs in control of the cytoskeleton,exocytosis, and cell death

MICALs form an evolutionary conserved family of multidomain signal transduction proteins characterized by a flavoprotein monooxygenase domain. MICALs are being implicated in the regulation of an increasing number of molecular and cellular processes including cytoskeletal dynamics and intracellular trafficking. Intriguingly, some of these effects are dependent on the MICAL monooxygenase enzyme and redox signaling, while other functions rely on other parts of the MICAL protein. Recent breakthroughs in our understanding of MICAL signaling identify the ability of MICALs to bind and directly modify the actin cytoskeleton, link MICALs to the docking and fusion of exocytotic vesicles, and uncover MICALs as anti-apoptotic proteins. These discoveries could lead to therapeutic advances in neural regeneration, cancer, and other diseases.     

Levels of cytochromes in heart,liver, kidney and brain in the developing rat

Zusammenfassung Der Gehalt an Cytochromen (c+c ₁,aa ₃ undb) in Herz, Leber, Gehirn und Niere der Ratte wurde bestimmt. Ihre Vermehrung nach der Geburt erwies sich in den Geweben als relativ individuell. Die Vermehrung des ausserhalb der Mitochondrien synthetisierten Cytochromenc ging den übrigen, von der intramitochondrialen Proteinsynthese unabhängigen Cytochromen voraus.