Gitterkonstanten und Raumgruppe von Tetrammincuprisulfat

Summary The space-group of Cu(NH₃)₄SO₄·H₂O isD _2h ¹⁶ orD _2h ¹³ (D _2h ⁵ , D _2h ¹ ) with a=7,07, b=12,12, c=10,66 Å ± 1%.     

The X-ray analysis of the structure of rifamycin Y

Riassunto La struttura cristallina dellap-iodio anilide della rifamicina Y è stata determinata con metodi tridimensionali a temperatura ambiente. La cella elementare monoclina, gruppo spaziale P2₁, ha i parametria = 9,49,b = 18,96,c = 15,30 Å, = 90°48, e contiene due molecole.La costituzione e la configurazione della rifamicina Y, C₃₉H₄₇NO₁₅, risultano quindi determinate attraverso lo studio cristallografico della suap-iodio anilide. Anche molte informazioni sulla configurazione della rifamicina Y possono essere tratte dalla configurazione allo stato solido di questo suo derivato.

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A brief preliminary report on this structure was read at a meeting of the Accademia Nazionale dei Lincei, Rome, on 12th March 1966².     

Subatomic and atomic crystallographic studies of aldose reductase: implications for inhibitor binding

The determination of several of aldose reductase-inhibitor complexes at subatomic resolution has revealed new structural details, including the specific interatomic contacts involved in inhibitor binding. In this article, we review the structures of the complexes of ALR2 with IDD 594 (resolution: 0.66 Å, IC50 (concentration of the inhibitor that produced half-maximal effect): 30 nM, space group: P2¹), IDD 393 (resolution: 0.90 Å, IC50: 6 nM, space group: P1), fidarestat (resolution: 0.92 Å, IC50: 9 nM, space group: P2¹) and minalrestat (resolution: 1.10 Å, IC50: 73 nM, space group: P1). The structures are compared and found to be highly reproductible within the same space group (root mean square (RMS) deviations: 0.15 0.3 Å). The mode of binding of the carboxylate inhibitors IDD 594 and IDD 393 is analysed. The binding of the carboxylate head can be accurately determined by the subatomic resolution structures, since both the protonation states and the positions of the atoms are very precisely known. The differences appear in the binding in the specificity pocket. The high-resolution structures explain the differences in IC50, which are confirmed both experimentally by mass spectrometry measures of VC50 and theoretically by free energy perturbation calculations. The binding of the cyclic imide inhibitors fidarestat and minalrestat is also described, focusing on the observation of a Cl^- ion which binds simultaneously with fidarestat. The presence of this anion, binding also to the active site residue His110, leads to a mechanism in which the inhibitor can bind in a neutral state and then become charged inside the active site pocket. This mechanism can explain the excellent in vivo properties of cyclic imide inhibitors. In summary, the complete and detailed information supplied by the subatomic resolution structures can explain the differences in binding energy of the different inhibitors.     

CSTX-9, a toxic peptide from the spider Cupiennius salei: amino acid sequence, disulphide bridge pattern and comparison with other spider toxins containing the cystine knot structure

CSTX-9 (68 residues, 7530.9 Da) is one of the most abundant toxic polypeptides in the venom of the wandering spider Cupiennius salei. The amino acid sequence was determined by Edman degradation using reduced and alkylated CSTX-9 and peptides generated by cleavages with endoproteinase Asp-N and trypsin, respectively. Sequence comparison with CSTX-1, the most abundant and the most toxic polypeptide in the crude spider venom, revealed a high degree of similarity (53% identity). By means of limited proteolysis with immobilised trypsin and RP-HPLC, the cystine-containing peptides of CSTX-9 were isolated and the disulphide bridges were assigned by amino acid analysis, Edman degradation and nanospray tandem mass spectrometry. The four disulphide bonds present in CSTX-9 are arranged in the following pattern: 1-4, 2-5, 3-8 and 6-7 (Cys₆-Cys₂₁, Cys₁₃-Cys₃₀, Cys₂₀-Cys₄₈, Cys₃₂-Cys₄₆). Sequence comparison of CSTX-1 with CSTX-9 clearly indicates the same disulphide bridge pattern, which is also found in other spider polypeptide toxins, e.g. agatoxins (ω-AGA-IVA, ω-AGA-IVB, μ-AGA-I and μ-AGA-VI) from Agelenopsis aperta, SNX-325 from Segestria florentina and curtatoxins (CT-I, CT-II and CT-III) from Hololena curta. CSTX-1/CSTX-9 belong to the family of ion channel toxins containing the inhibitor cystine knot structural motif. CSTX-9, lacking the lysine-rich C-terminal tail of CSTX-1, exhibits a ninefold lower toxicity to Drosophila melanogaster than CSTX-1. This is in accordance with previous observations of CSTX-2a and CSTX-2b, two truncated forms of CSTX-1 which, like CSTX-9, also lack the C-terminal lysine-rich tail. Received 23 July 2001; accepted 31 July 2001     

Vitamin E,catalase, manganous or cobaltous ions and dithiothreitol protect against Tween 20-induced hemolysis of vitamin E-deficient chick and kid erythrocytes

Summary The effective Tween 20 concentration at which 70% hemolysis was achieved in vitro correlated with the plasma vitamin E content of chicks (r=0.85). Addition of catalase, MnCl₂, CoCl₂ or dithiothreitol in vitro showed significant protection against the hemolysis induced by Tween 20 in vitamin E-deficient chick and kid erythrocytes.     

Zur Wirkungsweise einiger Katalase-Inhibitoren

Summary The mechanism of catalase inhibition by CN^–, N ₃ ^– , and SH^– has been investigated by a polarographic method. CN^– has been found to inhibit reversibly by a coordinating mechanism, whereas N ₃ ^– and SH^– inhibits catalase irreversibly.     

The photoelectric theory of photosynthesis IV. the chromophore area of chlorophyll

Résumé La superficie de la coupe transversale de captation des photons, calculée à partir de l'absorptivité molaire par l'équation de Braude, est de 13,8 (Å)² pour la bande d'absorption principale de chlorophylle à 430 mµ. Cette superficie peut se comparer favorablement à la valeur 12,0 (Å)², calculée pour la superficie centrale circulaire Mg-N₄, de la chlorophylle, mais elle est, très nettement plus petite que la superficie du noyau carré de la porphyrine, qui est de 105 (Å)². Ce résultat est interprété comme preuve supplémentaire pour la théorie photoélectrique de photosynthèse, selon laquelle l'auteur a postulé que c'est l'atome Mg de chlorophylle qui est excité électroniquement par absorption de lumière.     

Aluminum-triggered structural modifications and aggregation of β-amyloids

We investigated the structural effects induced by Al³⁺ on different β-amyloid (Aβ) fragments at pH 7.4 and T= 25°C, with particular attention given to the sequences 1–40 and 1–42. Al³⁺ caused peptide enrichment in β sheet structure and formation of solvent-exposed hydrophobic clusters. These intermediates evolved to polymeric aggregates which organized in fibrillar forms in the case of the Al³⁺-Aβ_(1–42) complex. Comparative studies showed that Zn²⁺ and Cu²⁺ were much less efficient than Al³⁺ in stimulating the spontaneous aggregation/fibrillogenesis of Aβs. Studies with liposomes as membrane models showed dramatic changes in the structural properties of the lipid bilayer in the presence of Al³⁺-Aβ complexes, suggesting a major role of Al³⁺ in Aβ-induced cell dysfunction. Al³⁺ effects were abolished by desferrioxamine mesylate (DFO) only in solution. We concluded that, in vivo, DFO may act as a protective agent by preventing or reverting Aβ aggregation in the extracellular spaces.Received 29 March 2005; received after revision 10 May 2005; accepted 25 May 2005     

Identification of tyrosine-phosphorylated proteins of the mitochondrial oxidative phosphorylation machinery

The role of some serine/threonine kinases in the regulation of mitochondrial physiology is now well established, but little is known about mitochondrial tyrosine kinases. We showed that tyrosine phosphorylation of rat brain mitochondrial proteins was increased by in vitro addition of ATP and H₂O₂, and also during in situ ATP production at state 3, and maximal reactive oxygen species production. The Src kinase inhibitor PP2 decreased tyrosine phosphorylation and respiratory rates at state 3. We found that the 39-kDa subunit of complex I was tyrosine phosphorylated, and we identified putative tyrosine-phosphorylated subunits for the other complexes. We also have strong evidence that the FoF1-ATP synthase α chain is probably tyrosine-phosphorylated, but demonstrated that the β chain is not. The tyrosine phosphatase PTP 1B was found in brain but not in muscle, heart or liver mitochondria. Our results suggest that tyrosine kinases and phosphatases are involved in the regulation of oxidative phosphorylation.Received 7 January 2005; received after revision 19 April 2005; accepted 22 April 2005     

Exact test for opposite trends of probability changes in one or several 3×2 tables

Zusammenfassung Der «Likelihood»-Quotiententest wird auf einer 3×2-Kontigenztafel mit unbekannten Wahrscheinlichkeitenp _ij (i=1,2,3;j=1,2) angewandt, um die Hypothese H₀:p _i1=p _i2 (i=1,2,3) gegen die alternative Hypothese H₁:p ₁₁>p ₁₂ p ₃₁<p ₃₂ zuprüfen, und zwar wenn kleine Stichproben vorhanden sind. Ausserdem wird die Kombination solcher Tests behandelt. Als Beispiel wird diese Testtheorie beim Wahlverhalten des Kabeljaus im Dressurversuch über akustische Lokalisation in zwei Stimulussituationen verwendet.

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The close cooperation with Drs.E. Meelis, Institute of Theoretical Biology Leyden, The Netherlands, in applying the likelihood ratio test to this case is gratefully acknowledged.

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The author is greatly indebted to Dr.J. Oosterhoff, Mathematical Institute, University of Nijmegen, The Netherlands, for introducing the subclasses 1b and 1c in the computation of vector and for the explicit expressions in these cases which eliminated the need for a numerical optimization. Further more valuable remarks regarding the combination problem were obtained.     

Robust estimation of conditional variance of time series using density power divergences

Suppose Z _t is the square of a time series Y _t whose conditional mean is zero. We do not specify a model for Y _t , but assume that there exists a p ×1 parameter vector Φ such that the conditional distribution of Z _t | Z _{t ?1} is the same as that of , where Z _{t ?1}=(Z _{t ?1},…,Z _{t ?p} )^T for some lag p ?1. Consequently, the conditional variance of Y _t is some function of . To estimate Φ , we propose a robust estimation methodology based on density power divergences (DPD) indexed by a tuning parameter α ∈[0,1], which yields a continuum of estimators, , where α controls the trade‐off between robustness and efficiency of the DPD estimators. For each α , is shown to be strongly consistent. We develop data‐dependent criteria for the selection of optimal α and lag p in practice. We illustrate the usefulness of our DPD methodology via simulation studies for ARCH‐type models, where the errors are drawn from a gross‐error contamination model and the conditional variance is a linear and/or nonlinear function of . Furthermore, we analyze the Chicago Board Options Exchange Dow Jones volatility index data and show that our DPD approach yields viable models for the conditional variance, which are as good as, or superior to, ARCH/GARCH models and two other divergence‐based models in terms of in‐sample and out‐of‐sample forecasts.     

Eine Absorptionsschicht der hohen Atmosphäre?

Summary The varying intensity of the shortest wave-length 2863 Å of the solar spectrum points to the possibility that labile absorption spectra exist in the higher atmosphere. As spectrographs mounted on V-2 rockets have showen that at a height of 55 km an absorption exists around 2800 Å besides the strong Frauenhofer-lines, and as the termination of the solar spectrum at 2400 Å appears remarkably abrupt, we may suspect a new absorption in the high atmosphere, for which possibly the oxides of nitrogen, primarily the NO ₂ ⁺ or the NO⁺ ion, are responsible.     

Involvement of reactive oxygen species in the microsomal S-oxidation of thiobenzamide

Summary Superoxide dismutase, catalase and methional proved capable of inhibiting the microsomal oxidation of thiobenzamide, which is most probably catalyzed by the flavin-containing monooxygenase. This indicates that excited oxygen species (e. g.·O ₂ ^– , H₂O₂, ·OH) are involved in the catalytic cycle of this enzymatic reaction. CO, which inhibits the cytochrome P-450-dependent oxygen radical formation, had no effect on the oxidation reaction, suggesting that the source of the reactive oxygen species is not the microsomal mixed-function oxidase.     

Respiratory burst in peritoneal exudate cells in response to a modified tuftsin

Intraperitoneal administration of tuftsin-M [Thr–Lys–Pro–Arg–NH–(CH₂)₂–NH–CO–C₁₅H₃₁] to Balb/C mice has been shown to induce a respiratory burst in the peritoneal exudate cells. The macrophages exhibited enhanced levels of O₂ ^–, H₂O₂, NADPH oxidase and myeloperoxidase, but the activities of superoxide dismutase, catalase and glutathione peroxidase remained virtually unchanged. The magnitude of the oxidative burst depended directly on the dose of tuftsin-M; higher activity was observed at higher doses of the peptide. Tuftsin-M enhanced the generation of both O ₂ ^– and H₂O₂ under in vitro conditions, as did phorbol myristate acetate. These results suggest that tuftsin-M could enhance non-specific defence against infections by activating the macrophages.     

Geometrical constructions equivalent to non-linear algebraic transformations of the plane in Newton's early papers

Summary The theory of constructive formation of plane algebraic curves in Newton's writings is discussed in § 1: the apparatus by which Newton forms the curves, Newton's theorems on forming unicursal curves, his theory of conics, and his theory of (m, n) correspondence. Special Cremona plane and space transformations obtained by Newton's organic method are dealt with in § 2. The article ends with § 3, which shows two different directions in the theory of the constructive formation of plane algebraic curves in the XVIII-XIXth centuries. A synopsis is appended.Abbreviations MPN The Mathematical Papers of Isaac Newton, edited by D. T. Whiteside, Vols. 1–3, Cambridge, 1967–1969 - Hudson H. Hudson, Cremona Transformations in Plane and Space, Cambridge, 1927 - PT (abridged) Philosophical Transactions of the Royal Society 1665–1800 (abridged), London, 1809 - Andreev ₁ K. A. Andreev, On geometrical correspondences ... (in Russian), Moscow, 1879 - Andreev ₂ K. A. Andreev, On the Geometrical Formation of Plane Curves (in Russian), Kharkov, 1875     

Participation of ACTH1–10 and ACTH4–10 on the melatonin modulation of benzodiazepine receptors in rat cerebral cortex

In this study, we examined the effect of intracerebroventricular (i.c.v) injection of melatonin and/or ACTH_1–10 and ACTH_4–10 on [³H]flunitrazepam binding sites in the cerebral cortex of hypophysectomized rats. Hypophysectomy increased the B_max (maximum number of binding sites) of benzodiazepine (BNZ) receptors for at least 7 days after surgery, without changing K_D (dissociation constant). The i.c.v. injection of melatonin to hypophysectomized rats significantly increased B_max, whereas the same doses of melatonin were ineffective in sham-operated animals. In both cases, K_D values were unchanged. The i.c.v injection of ACTH_1–10 to hypophysectomized animals significantly increased B_max, an effect that was enhanced by simultaneous i.c.v. injection of ACTH_1–10+melatonin, reaching higher values of B_max than the i.c.v. injection of these hormones individually. No significant changes in K_D values were found after ACTH_1–10 and/or melatonin administration. However, the i.c.v. injection of ACTH_4–10 to hypophysectomized rats did not change B_max, although it significantly increased K_D values, indicating a decrease in the BNZ binding affinity. Melatonin injection counteracted this effect of ACTH_4–10, returning K_D to the control value. Moreover, although the lower dose of i.c.v. melatonin used, 10 ng, was unable to modify B_max of BNZ binding in the ACTH_4–10-injected group, the higher dose, 20 ng, significantly increased B_max. The results suggest that these ACTH-derived peptides can modulate the effect of melatonin on brain benzodiazepine receptors.     

C-peptide stimulates Na<Superscript>+</Superscript>, K<Superscript>+</Superscript>-ATPase via activation of ERK1/2 MAP kinases in human renal tubular cells

Proinsulin-connecting peptide (C-peptide) exerts physiological effects partially via stimulation of Na⁺, K⁺-ATPase. We determined the molecular mechanism by which C-peptide stimulates Na⁺, K⁺-ATPase in primary human renal tubular cells (HRTCs). Incubation of the cells with 5 nM human C-peptide at 37°C for 10 min stimulated ⁸⁶Rb⁺ uptake by 40% (p<0.01). The carboxy-terminal pentapeptide was found to elicit 57% of the activity of the intact molecule. In parallel with ouabain-sensitive ⁸⁶Rb⁺ uptake, C-peptide increased subunit phosphorylation and basolateral membrane (BLM) abundance of the Na⁺, K⁺-ATPase ₁ and ₁ subunits. The increase in BLM abundance of the Na⁺, K⁺-ATPase ₁ and ₁ subunits was accompanied by depletion of ₁ and ₁ subunits from the endosomal compartments. C-peptide action on Na⁺, K⁺-ATPase was ERK1/2-dependent in HRTCs. C-peptide-stimulated Na⁺, K⁺-ATPase activation, phosphorylation of ₁-subunit and translocation of ₁ and ₁ subunits to the BLM were abolished by a MEK1/2 inhibitor (20 M PD98059). C-peptide stimulation of ⁸⁶Rb⁺ uptake was also abolished by preincubation of HRTCs with an inhibitor of PKC (1 M GF109203X). C-peptide stimulated phosphorylation of human Na⁺, K⁺-ATPase subunit on Thr-Pro amino acid motifs, which form specific ERK substrates. In conclusion, C-peptide stimulates sodium pump activity via ERK1/2-induced phosphorylation of Thr residues on the subunit of Na⁺, K⁺-ATPase.Received 15 June 2004; received after revision 14 September 2004; accepted 14 September 2004     

Cyanobacterial psbA gene family: optimization of oxygenic photosynthesis

The D1 protein of Photosystem II (PSII), encoded by the psbA genes, is an indispensable component of oxygenic photosynthesis. Due to strongly oxidative chemistry of PSII water splitting, the D1 protein is prone to constant photodamage requiring its replacement, whereas most of the other PSII subunits remain ordinarily undamaged. In cyanobacteria, the D1 protein is encoded by a psbA gene family, whose members are differentially expressed according to environmental cues. Here, the regulation of the psbA gene expression is first discussed with emphasis on the model organisms Synechococcus sp. and Synechocystis sp. Then, a general classification of cyanobacterial D1 isoforms in various cyanobacterial species into D1_m, D1:1, D1:2, and D1′ forms depending on their expression pattern under acclimated growth conditions and upon stress is discussed, taking into consideration the phototolerance of different D1 forms and the expression conditions of respective members of the psbA gene family.     

ADP receptor P2Y13 induce apoptosis in pancreatic β-cells

Pancreatic β-cell loss represents a key factor in the pathogenesis of diabetes. Since the influence of purinergic signaling in β-cell apoptosis has not been much investigated, we examined the role of the ADP receptor P2Y₁₃ using the pancreatic insulinoma-cell line MIN6c4 as a model system. Real time-PCR revealed high expression of the ADP receptors P2Y₁ and P2Y₁₃. Adding the ADP analogue, 2MeSADP, to MIN6c4 cells induced calcium influx/mobilization and inhibition of cAMP production by activation of P2Y₁ and P2Y₁₃, respectively. 2MeSADP reduced cell proliferation and increased Caspase-3 activity; both these effects could be fully reversed by the P2Y₁₃ receptor antagonist MRS2211. We further discovered that blocking the P2Y₁₃ receptor results in enhanced ERK1/2, Akt/PKB and CREB phosphorylation mechanisms involved in β-cell survival. These results indicate that P2Y₁₃ is a proapoptotic receptor in β-cells as the P2Y₁₃ receptor antagonist MRS2211 is able to protect the cells from ADP induced apoptosis.