Dopamine in the visual cortex of the cat

The endogenous content of noradrenaline (NA) and dopamine (DA) was determined by radioenzymatic assays in three different areas of the occipital (visual) cortex, in normal cats as well as in DA-deafferented animals. The use of HPLC methodology enabled us to detect and measure in addition two metabolites of DA: 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), thus confirming the existence of a DA innervation in this cortical region.     

Recent observations on the structure and the properties of yeast NMN adenylyltransferase

Summary A homogeneous preparation of yeast NMN adenylyltransferase (EC 2.7.7.1) showed microheterogeneity, which was revealed by FPLC (Fast Protein Liquid Chromatography) ion exchange chromatography. The resolved components have been characterized with respect to electrophoretic behavior and adenine content. The results led to a hypothesis about a possible role of poly(ADP-ribosylation) in modulating the enzyme activity.     

On the genesis of the soil mantle of the region of Manaus,Central Amazonia,Brazil

Summary The dynamics of the forest to the north of Manaus is tightly linked to that of the soil. The latosol that covers the plateau, which supports a dense forest, consists from top to bottom of: (a) a brown, clayey organic horizon (0.3 m), (b) a yellow horizon, very rich in clay but permeable (from 0.3 to 4 m), (c) a nodular horizon rich in Al and Fe oxides (from 4 to 9 m), and (d) a horizon which still preserves the sedimentary structures of the parent sandstone, where quartz is intensely dissolved and kaolinite crystallizes in pores. In perfectly flat areas, the clay of the organic horizon is destroyed by acidocomplexolysis, and the dissolved Al is transported vertically by the drainage water. A part of this Al is used to make the gibbsite nodules of horizon (c), and the rest is used to make kaolinite in horizon (d). Because aluminum is thus conserved within any vertical prism, the rate of destruction of horizon (a) is equivalent to the rate of advance of the kaolinization zone into the sediment: the latosol is said to be in equilibrium, the surface remains perfectly flat as it slowly sinks, the quantity of kaolinite increases with time, and the silica released by quartz dissolution in the whole profile is exported by drainage water to the water table. In contrast, near drainage axes, however small initially, the drainage becomes inclined toward the axis. Part of the Al released by acidocomplexolysis of horizon (a) is now exported to rivers, and Al is no longer conserved within any given prism. The rate of advance of the kaolinization zone (d) into the sediment now becomes less than the rate of destruction of horizon (a) and the surface sinks faster than that of the surrounding plateau. After this differential podzolization has gone on long enough, it creates a network of geochemical valleys characterized by convex slopes and bounded by sandy soils (campinas). The vegetation becomes sparser and sparser. At the end, only some bushes and lichens survive on the white sand.Acknowledgments. The authors are indebted to Dr E. Merino (Dept. of Geology, Indiana University) for helpful criticisms and suggestions. This research was carried out in I.N.P.A. (Instituto Nacional de Pesquisas da Amazonia) and was financially supported by the CNPq-CNRS/ORSTOM conv.     

Direct evidence that the N-terminal extensions of the TAP complex act as autonomous interaction scaffolds for the assembly of the MHC I peptide-loading complex

The loading of antigenic peptides onto major histocompatibility complex class I (MHC I) molecules is an essential step in the adaptive immune response against virally or malignantly transformed cells. The ER-resident peptide-loading complex (PLC) consists of the transporter associated with antigen processing (TAP1 and TAP2), assembled with the auxiliary factors tapasin and MHC I. Here, we demonstrated that the N-terminal extension of each TAP subunit represents an autonomous domain, named TMD(0), which is correctly targeted to and inserted into the ER membrane. In the absence of coreTAP, each TMD(0) recruits tapasin in a 1:1 stoichiometry. Although the TMD(0)s lack known ER retention/retrieval signals, they are localized to the ER membrane even in tapasin-deficient cells. We conclude that the TMD(0)s of TAP form autonomous interaction hubs linking antigen translocation into the ER with peptide loading onto MHC I, hence ensuring a major function in the integrity of the antigen-processing machinery.     

Effect of stress on choline acetyltransferase activity of the brain and the adrenal of the rat

Choline acetyltransferase (ChAT) activity was determined in cerebral cortex, hypothalamus, hippocampus, cerebellum, medulla oblongata, midbrain and adrenal gland of rats exposed to acute or chronic stress. The exposure of animals to acute immobilization and cold stress (4°C) for one hour resulted in a significant decline of ChAT activity in all brain regions examined except for the medulla oblongata. Moreover, the exposure to acute stress resulted in significant increase of the same enzyme in the adrenal gland. However, chronic exposure of animals to cold stress (4°C) for 7 days resulted in no significant changes of ChAT activity in all tissues examined except for a decline in the midbrain and an increase in the medulla oblongata. The administration of corticosterone (2.0 mg/kg) 1 h prior to sacrificing caused an effect similar to that of acute stress on ChAT activity in all brain regions except for the hypothalamus and the cerebellum. It was concluded from this experiment that stress-induced changes in the ChAT activity of specific brain regions might be mediated by the adrenal steroids.This work was supported by a grant from the National Aeronautics and Space Administration (NSG 2183 and NAG 2-411), a grant from the National Institutes of Health (NIH RR 0811) and a grant from the Division of Research Resources (NIH grant RR 03020).     

The accuracy of aminoacylation--ensuring the fidelity of the genetic code

The fidelity of protein biosynthesis rests not only on the proper interaction of the messenger RNA codon with the anticodon of the tRNA, but also on the correct attachment of amino acids to their corresponding (cognate) transfer RNA (tRNA) species. This process is catalyzed by the aminoacyl-tRNA synthetases which discriminate with remarkable selectivity amongst many structurally similar tRNAs. The basis for this highly specific recognition of tRNA by these enzymes (also referred to as 'tRNA identity') is currently being elucidated by genetic, biochemical and biophysical techniques. At least two factors are important in determining the accuracy of aminoacylation: a) 'identity elements' in tRNA denote nucleotides in certain positions crucial for protein interactions determining specificity, and b) the occurrence in vivo of competition between synthetases for a particular tRNA which may have ambiguous identity.     

The metabolism of the soil fumigant 1,2-dibromo-3-chloropropane in the rat

The soil fumigant 1,2-dibromo-3-chloropropane (I) undergoes hydrolysis in the rat to a series of epoxide metabolites. Alkylation of glutathione by these epoxides produces 2 urinary metabolites identified as the mercapturic acids VI (R=COCH3) and VII (R-COCH3). Hydrolysis of the epoxides produces the male antifertility agents alpha-chlorohydrin (IX, X-Cl) and alpha-bromohydrin (IX, X-Br) which are oxidatively metabolized to oxalic acid (XII), thus causing renal damage. These metabolic pathways can explain the toxic nature of the fumigant as a carcinogen, a male chemosterilant and as an agent causing kidney damage.     

Regulation of the retinal interphotoreceptor matrix Na by the retinal pigment epithelium during the light response

We examined the rabbit retinal pigment epithelium (RPE) for Na transport properties which would allow it to buffer undesirable changes in Na concentrations in the interphotoreceptor matrix (IPM) during light and dark cycles. The RPE is selectivity permeable to sodium. Open and short circuit transport studies with RPE indicate a circulating (choroid to retina and back) Na current which does not compromise the electrical integrity of the blood brain barrier but together with the Na permeselectivity is of sufficient magnitude to buffer both upwards and downwards movements of IPM [Na] during light or dark responses.     

The cross-talk between the urokinase receptor and fMLP receptors regulates the activity of the CXCR4 chemokine receptor

The receptor (CXCR4) for the stromal-derived factor-1 (SDF1) and the urokinase-receptor (uPAR) are up-regulated in various tumors. We show that CXCR4-transfected cells migrate toward SDF1 on collagen (CG) and do not on vitronectin (VN). Co-expression of cell-surface uPAR, which is a VN receptor, impairs SDF1-induced migration on CG and allows migration on VN. Blocking fMLP receptors (fMLP-R), alpha-v integrins or the uPAR region capable to interact with fMLP-Rs, impairs migration of uPAR/CXCR4-transfected cells on VN and restores their migration on CG. uPAR co-expression also reduces the adherence of CXCR4-expressing cells to various components of the extracellular matrix (ECM) and influences the partitioning of beta1 and alpha-v integrins to membrane lipid-rafts, affecting ECM-dependent signaling. uPAR interference in CXCR4 activity has been confirmed in cells from prostate carcinoma. Our results demonstrate that uPAR expression regulates the adhesive and migratory ability of CXCR4-expressing cells through a mechanism involving fMLP receptors and alpha-v integrins.     

Redox modulation of the NMDA receptor

Redox modulation has been recognized to be an important mechanism of regulation for the N-methyl-D-aspartate (NMDA) receptor. Sulfhydryl reducing agents enhance, whereas oxidizing agents decrease, NMDA-evoked currents. Multiple cysteine residues located in different NMDA receptor subunits have been identified as molecular determinants underlying redox modulation. The NMDA receptor is also regulated by nitric oxide (NO)-related species directly, not involving cyclic GMP, but the molecular mechanism of this action has heretofore not been entirely clear. The confusion arose at least partly due to the fact that various redox forms of NO (NO+, NO*, NO-, each having an additional electron compared with the previous) have distinct mechanisms of action. Recently, a critical cysteine residue (Cys 399) on the NR2A subunit has been shown to react under physiological conditions with NO by S-nitrosylation (transfer of the NO+ to cysteine thiol) or by reaction with NO- (nitroxyl anion) to underlie this form of modulation.     

Hormonal facilitation in the release of sperm from the spermatheca of the red-spotted newt

Several neurotransmitters and hormones with potential to trigger a simultaneous contraction of the oviducts and the spermathecal myoepithelium were examined. Saline (0.05 ml), or 0.05 ml saline plus acetylcholine (9 mg), norepinephrine (50 micrograms), arginine-vasotocin (25 units), prostaglandin F2 alpha (3 micrograms) were injected into the spermathecal region of female newts (n = 24 per group). The numbers of sperm present in the cloacae of prostaglandin-injected animals (107 +/- 30 SEM) were significantly greater than the numbers detected in saline (27 +/- 5 SEM) and in uninjected (14 +/- 3 SEM) controls. Smaller and less consistent increases in the numbers of sperm were detected in the vasotocin- and norepinephrine-injected groups. Study of sections from ovulating female newts failed to produce evidence that pressure from the passage of ova through the posterior portion of the oviduct forced sperm from the spermatheca. Observations indicate an active role for the spermathecal myoepithelium in the discharge of stored sperm and of a role for prostaglandin F2 alpha in triggering that discharge.     

Lack of participation of cytoplasmic choline in the synthesis of acetylcholine in the striatal synaptosomes of the rat]

Synaptosomes prepared from Rat striatum were loaded with (14C) choline at 0 degrees C in the course of a 60 min. preincubation. After the removal, by washing, of the extracellular molecules, synaptosomes were incubated 5 min. at 37 degrees C in the presence of (3H) choline. The measurement of the amounts of (3H) ACh and of (14C) ACh formed allowed us to conclude that the acetylation of the molecules of choline was directly coupled to their passage through the synaptosomal membrane.     

Effect of stress on choline acetyltransferase activity of the brain and the adrenal of the rat.

Choline acetyltransferase (ChAT) activity was determined in cerebral cortex, hypothalamus, hippocampus, cerebellum, medulla oblongata, midbrain and adrenal gland of rats exposed to acute or chronic stress. The exposure of animals to acute immobilization and cold stress (4 degrees C) for one hour resulted in a significant decline of ChAT activity in all brain regions examined except for the medulla oblongata. Moreover, the exposure to acute stress resulted in significant increase of the same enzyme in the adrenal gland. However, chronic exposure of animals to cold stress (4 degrees C) for 7 days resulted in no significant changes of ChAT activity in all tissues examined except for a decline in the midbrain and an increase in the medulla oblongata. The administration of corticosterone (2.0 mg/kg) 1 h prior to sacrificing caused an effect similar to that of acute stress on ChAT activity in all brain regions except for the hypothalamus and the cerebellum. It was concluded from this experiment that stress-induced changes in the ChAT activity of specific brain regions might be mediated by the adrenal steroids.     

Further evidence for the existence of a bottleneck in the metabolism of Saccharomyces cerevisiae

The growth physiology of Saccharomyces cerevisiae strains H1022 and Whi2+ has been studied in aerobic batch and continuous (chemostat) cultures. Results from the measurement of biomass and medium components (off-line) together with oxygen, carbon dioxide and heat measurements (on-line) have been used in an attempt to explore the existence of 'overflow' or 'bottleneck' metabolism as opposed to catabolite repression (Crabtree effect) in these strains. Chemostat experiments indicated that specific oxygen uptake rate (qO2) was linearly related to the dilution rate (D) at values below the critical dilution rate (D crit), becoming constant above D crit, which is in agreement with the bottleneck theory. However, batch culture experiments indicated negligible oxygen consumption during the initial glucose growth phase, the culture exhibiting purely anaerobic metabolism. The bottleneck theory would propose that qO2 has a constant (maximum) value under these conditions. The results presented here suggest that while the bottleneck theory can be adequately used to describe chemostat growth of S. cerevisiae, some other control mechanism must be operating under conditions of high glucose concentrations, such as those initially prevailing in the batch culture experiments.     

The non-relativistic limits of the Maxwell and Dirac equations: the role of Galilean and gauge invariance

The aim of this paper is to illustrate four properties of the non-relativistic limits of relativistic theories: (a) that a massless relativistic field may have a meaningful non-relativistic limit, (b) that a relativistic field may have more than one non-relativistic limit, (c) that coupled relativistic systems may be “more relativistic” than their uncoupled counterparts, and (d) that the properties of the non-relativistic limit of a dynamical equation may differ from those obtained when the limiting equation is based directly on exact Galilean kinematics. These properties are demonstrated through an examination of the non-relativistic limit of the familiar equations of first-quantized QED, i.e., the Dirac and Maxwell equations. The conditions under which each set of equations admits non-relativistic limits are given, particular attention being given to a gauge-invariant formulation of the limiting process especially as it applies to the electromagnetic potentials. The difference between the properties of a limiting theory and an exactly Galilean covariant theory based on the same dynamical equation is demonstrated by examination of the Pauli equation.     

On the notion of free will in the Free Will Theorem

The (Strong) Free Will Theorem (fwt) of Conway and Kochen (2009) on the one hand follows from uncontroversial parts of modern physics and elementary mathematical and logical reasoning, but on the other hand seems predicated on an undefined notion of free will (allowing physicists to “freely choose” the settings of their experiments). This makes the theorem philosophically vulnerable, especially if it is construed as a proof of indeterminism or even of libertarian free will (as Conway & Kochen suggest).However, Cator and Landsman (Foundations of Physics 44, 781–791, 2014) previously gave a reformulation of the fwt that does not presuppose indeterminism, but rather assumes a mathematically specific form of such “free choices” even in a deterministic world (based on a non-probabilistic independence assumption). In the present paper, which is a philosophical sequel to the one just mentioned, I argue that the concept of free will used in the latter version of the fwt is essentially the one proposed by Lewis (1981), also known as ‘local miracle compatibilism’ (of which I give a mathematical interpretation that might be of some independent interest also beyond its application to the fwt). As such, the (reformulated) fwt in my view challenges compatibilist free will à la Lewis (albeit in a contrived way via bipartite epr-type experiments), falling short of supporting libertarian free will.     

Kepler: Analogies in the search for the law of refraction

This paper examines the methodology used by Kepler to discover a quantitative law of refraction. The aim is to argue that this methodology follows a heuristic method based on the following two Pythagorean principles: (1) sameness is made known by sameness, and (2) harmony arises from establishing a limit to what is unlimited. We will analyse some of the author's proposed analogies to find the aforementioned law and argue that the investigation's heuristic pursues such principles.     

Neurosecretory cells of the globuli I and the protocephalic neurosecretory pathway of the myriapods, diplodods. Preliminary observations on the Polydesmida, Platyrrhacidae, the Nematophora Lysiopetalidae, the Spirostreptida and the Spirobolida]

The Diplopods studied by the author and more particularly Platyrrhacidae, Lysiopetalidae, Spirostreptida and Spirobolida, show neurosecretory cells near the globuli I. The whole of his observations induces the author to admit a structural plan common to all the Diplopods: neurosecretory cells of globuli I--(NOG) nerve--neurohemal organ (Gabe's organ). Moreover he makes an attempt to compare his observations with those concerning another group of Myriapods: the Chilopods.     

Drugs of the future: the hormone relaxin

The peptide hormone relaxin is emerging as a multi-functional factor in a broad range of target tissues including several non-reproductive organs, in addition to its historical role as a hormone of pregnancy. This review discusses the evidence that collectively demonstrates the many diverse and vital roles of relaxin: the homeostatic role of endogenous relaxin in mammalian pregnancy and ageing; its gender-related effects; the therapeutic effects of relaxin in the treatment of fibrosis, inflammation, cardioprotection, vasodilation and wound healing (angiogenesis) amongst other pathophysiological conditions, and its potential mechanism of action. Furthermore, translational issues using experimental models (to humans) and its use in various clinical trials, are described, each with important lessons for the design of future trials involving relaxin. The diverse physiological and pathological roles for relaxin have led to the search for its significance in humans and highlight its potential as a drug of the future. Received 12 December 2006; received after revision 12 February 2007; accepted 15 March 2007     

The metabolism of the soil fumigant 1,2-dibromo-3-chloropropane in the rat

Summary The soil fumigant 1,2-dibromo-3-chloropropane (I) undergoes hydrolysis in the rat to a series of epoxide metabolites. Alkylation of glutathione by these epoxides produces 2 urinary metabolites identified as the mercapturic acids VI (R=COCH₃) and VII (R=COCH₃). Hydrolysis of the epoxides produces the male antifertility agentsa-chlorohydrin (IX, X=Cl) anda-bromohydrin (IX, X=Br) which are oxidatively metabolized to oxalic acid (XII), thus causing renal damage. These metabolic pathways can explain the toxic nature of the fumigant as a carcinogen, a male chemosterilant and as an agent causing kidney damage.This work was supported in part by the National Health and Medical Research Council of Australia.