Epigenetics: a link between addiction and social environment

The detrimental effects of drug abuse are apparently not limited to individuals but may also impact the vulnerability of their progenies to develop addictive behaviours. Epigenetic signatures, early life experience and environmental factors, converge to influence gene expression patterns in addiction phenotypes and consequently may serve as mediators of behavioural trait transmission between generations. The majority of studies investigating the role of epigenetics in addiction do not consider the influence of social interactions. This shortcoming in current experimental approaches necessitates developing social models that reflect the addictive behaviour in a free-living social environment. Furthermore, this review also reports on the advancement of interventions for drug addiction and takes into account the emerging roles of histone deacetylase (HDAC) inhibitors in the etiology of drug addiction and that HDAC may be a potential therapeutic target at nucleosomal level to improve treatment outcomes.     

Nicolas-Auguste Tissot: a link between cartography and quasiconformal theory

Nicolas-Auguste Tissot (1824–1897) published a series of papers on cartography in which he introduced a tool which became known later on, among geographers, under the name of the Tissot indicatrix. This tool was broadly used during the twentieth century in the theory and in the practical aspects of the drawing of geographical maps. The Tissot indicatrix is a graphical representation of a field of ellipses on a map that describes its distortion. Tissot studied extensively, from a mathematical viewpoint, the distortion of mappings from the sphere onto the Euclidean plane that are used in drawing geographical maps, and more generally he developed a theory for the distortion of mappings between general surfaces. His ideas are at the heart of the work on quasiconformal mappings that was developed several decades after him by Grötzsch, Lavrentieff, Ahlfors and Teichmüller. Grötzsch mentions the work of Tissot, and he uses the terminology related to his name (in particular, Grötzsch uses the Tissot indicatrix). Teichmüller mentions the name of Tissot in a historical section in one of his fundamental papers where he claims that quasiconformal mappings were used by geographers, but without giving any hint about the nature of Tissot’s work. The name of Tissot is missing from all the historical surveys on quasiconformal mappings. In the present paper, we report on this work of Tissot. We shall mention some related works on cartography, on the differential geometry of surfaces, and on the theory of quasiconformal mappings. This will place Tissot’s work in its proper context.     

The emerging link between O-GlcNAcylation and neurological disorders

O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is involved in the regulation of many cellular cascades and neurological diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke. In the brain, the expression of O-GlcNAcylation is notably heightened, as is that of O-linked N-acetylglucosaminyltransferase (OGT) and β-N-acetylglucosaminidase (OGA), the presence of which is prominent in many regions of neurological importance. Most importantly, O-GlcNAcylation is believed to contribute to the normal functioning of neurons; conversely, its dysregulation participates in the pathogenesis of neurological disorders. In neurodegenerative diseases, O-GlcNAcylation of the brain’s key proteins, such as tau and amyloid-β, interacts with their phosphorylation, thereby triggering the formation of neurofibrillary tangles and amyloid plaques. An increase of O-GlcNAcylation by pharmacological intervention prevents neuronal loss. Additionally, O-GlcNAcylation is stress sensitive, and its elevation is cytoprotective. Increased O-GlcNAcylation ameliorated brain damage in victims of both trauma-hemorrhage and stroke. In this review, we summarize the current understanding of O-GlcNAcylation’s physiological and pathological roles in the nervous system and provide a foundation for development of a therapeutic strategy for neurological disorders.     

Partial purification and some properties of a nucleoside phosphotransferase of chick embryos

Summary A nucleoside phosphotransferase purified about 40fold from chick embryos utilizes efficiently as phosphate donors deoxyribonucleoside and pyrimidine ribonucleoside monophosphates, whereas the pyrimidine deoxyribonucleoside appear to be the preferred acceptors of phosphate. The enzyme is very unstable to heat, dilution and dialysis. A marked enhancement in the stability is caused by nucleotides and it seems associated with the formation of an aggregated state of the protein.     

Asymmetry in the link between the yield spread and industrial production: threshold effects and forecasting

We analyse the nonlinear behaviour of the information content in the spread for future real economic activity. The spread linearly predicts one‐year‐ahead real growth in nine industrial production sectors of the USA and four of the UK over the last 40 years. However, recent investigations on the spread–real activity relation have questioned both its linear nature and its time‐invariant framework. Our in‐sample empirical evidence suggests that the spread–real activity relationship exhibits asymmetries that allow for different predictive power of the spread when past spread values were above or below some threshold value. We then measure the out‐of‐sample forecast performance of the nonlinear model using predictive accuracy tests. The results show that significant improvement in forecasting accuracy, at least for one‐step‐ahead forecasts, can be obtained over the linear model. Copyright © 2004 John Wiley & Sons, Ltd.     

Acyl-CoA thioesterase 9 (ACOT9) in mouse may provide a novel link between fatty acid and amino acid metabolism in mitochondria

Acyl-CoA thioesterase (ACOT) activities are found in prokaryotes and in several compartments of eukaryotes where they hydrolyze a wide range of acyl-CoA substrates and thereby regulate intracellular acyl-CoA/CoA/fatty acid levels. ACOT9 is a mitochondrial ACOT with homologous genes found from bacteria to humans and in this study we have carried out an in-depth kinetic characterization of ACOT9 to determine its possible physiological function. ACOT9 showed unusual kinetic properties with activity peaks for short-, medium-, and saturated long-chain acyl-CoAs with highest V _max with propionyl-CoA and (iso) butyryl-CoA while K _cat/K _m was highest with saturated long-chain acyl-CoAs. Further characterization of the short-chain acyl-CoA activity revealed that ACOT9 also hydrolyzes a number of short-chain acyl-CoAs and short-chain methyl-branched CoA esters that suggest a role for ACOT9 in regulation also of amino acid metabolism. In spite of markedly different K _ms, ACOT9 can hydrolyze both short- and long-chain acyl-CoAs simultaneously, indicating that ACOT9 may provide a novel regulatory link between fatty acid and amino acid metabolism in mitochondria. Based on similar acyl-CoA chain-length specificities of recombinant ACOT9 and ACOT activity in mouse brown adipose tissue and kidney mitochondria, we conclude that ACOT9 is the major mitochondrial ACOT hydrolyzing saturated C₂-C₂₀-CoA in these tissues. Finally, ACOT9 activity is strongly regulated by NADH and CoA, suggesting that mitochondrial metabolic state regulates the function of ACOT9.     

Correlation between sensitivity to trypaflavine and DNA base composition in mutants ofBacterium paracoli 5099

Bacterium paracoli 5099 , , .     

Relationships between the chemical structures and the biological properties of the posterior pituitary hormones and their synthetic analogues

Résumé Afin de mettre en évidence l'influence de faibles modifications de structure sur les propriétés biologiques, les auteurs comparent, à l'aide d'une série de tableaux systématiques, les structures chimiques et les propriétés pharmacologiques des hormones post-hypophysaires avec celles de près de quarante de leurs analogues synthétiques, qui ont été étudiés d'une manière approfondie. Cette confrontation montre qu'il est possible de découvrir quelques relations limitées entre la spécificité biologique de ces corps et certaines particularités de leur structure.     

7a-Aza-B-homo[7a, 7-d]tetrazole analogues of progesterone and testosterone

Summary The tetrazole analogues of progesterone and testosterone, namely, 7a-aza-B-homo-4-pregneno[7a, 7-d]tetrazole-3,20-dione (5) and 3-oxo-7a-aza-B-homo-4-androsteno[7a, 7-d]tetrazol-17-yl acetate (8), have been prepared which are worthy of biological testing.Part XLIII in the series Steroids and Related Studies. For Part XLII see H. Singh and K.K. Bhutani, Indian J. Chem. in press.     

The deamino derivatives of [4-threonine]-oxytocin and [4-threonine]-mesotocin; Analogs possessing a surprising spectrum of diminished pharmacological activities

Zusammenfassung Synthese (Merrifield-Methode) und pharmakologische Eigenschaften der Desamino-Derivate von (4-Threonin)-Oxytocin und (4-Threonin)-Mesoxytocin werden beschrieben.

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This work was supported in part by the Medical College of Ohio, a Contract (No. 69-2193) from the Center for Population Research of the National Institute of Child Health and Human Development, Research Grants from the National Science Foundation (No. GB-4932), the National Institute of Arthritis and Metabolic Diseases (No. AM-01940) and a General Research Support Grant to Columbia University from the National Institutes of Health. The authors wish to thank Mrs.Sara Crumm for performing the amino acid analyses and Mrs.Margot Acosta for performing the bioassays. An abstract of part of this work was presented at the 2nd American Peptide Symposium, Cleveland, Ohio, August 1970;M. Manning andW. H. Sawyer,Peptides (Ed.Saul Lande, Gordon and Breach, New York 1971), in press.     

A predicting system based on combining an adaptive predictor and a knowledge base as applied to a blast furnace

In this paper a system is proposed and applied to predicting silicon content in pig iron for a blast furnace. It combines an adaptive predictor with a knowledge base. On-line experiments show that the prediction accuracy of the system is much better than that of an experienced operator or of an adaptive predictor alone. Such a system will be helpful to operators in selecting desirable control methods.     

Hsp90 binds CpG oligonucleotides directly: implications for hsp90 as a missing link in CpG signaling and recognition

CpG motifs originating from bacterial DNA (CpG DNA) can act as danger signals for the mammalian immune system. These CpG DNA motifs like many other pathogen-associated molecular patterns are believed to be recognized by a member of the toll-like receptor family, TLR-9. Here we show results suggesting that heat shock protein 90 (hsp90) is also implicated in the recognition of CpG DNA. Hsp90 was characterized as a binder to oligodeoxynucleotides (ODNs) containing CpG motifs (CpG ODNs) after several purification steps from crude protein extracts of peripheral blood mononuclear cells. This finding was further supported by direct binding of CpG ODNs to commercially available human hsp90. Additionally, immunohistochemistry studies showed redistribution of hsp90 upon CpG ODN uptake. Thus, we propose that hsp90 can act as a ligand transfer molecule and/or play a central role in the signaling cascade induced by CpG DNA. Received 18 December 2002; accepted 6 January 2002 RID="*" ID="*"Corresponding author. B. Agerberth and G. H. Gudmundsson contributed equally to this work.