Left-handed helices for DNA: studies on poly[d(I-C)]

Earlier, we showed that, for the D form (n = 8 and h = 3.03 A, where n is number of nucleotide units per turn and h is height per nucleotide unit) of poly[d(A-T)], both right- and left-handed double helical models are stereochemically satisfactory and give good agreement with the observed fiber diffraction data. It was also noted that the conformations of the right- and left-handed D-DNA models are very similar to those of the right- and left-handed B-DNA models. This observation was consistent with the D leads to B transition in the solid phase. As a continuation of our earlier studies, we have carried out similar experiments with poly[d(I-C)]. We could obtain a crystalline D-form pattern (n = 8, h = 3.13 A) of the fiber at 75% relative humidity (r.h.); the hydrated (r.h. approximately equal to 95%) form of the same fiber gave the classical B-form pattern (n = 10, h = 3.40 A). In the present report, we show that both right- and left-handed double-helical models are consistent with the fiber diffraction data of poly[d(I-C)] in the D-form. Theoretical energy calculations also suggest that the right- and left-handed B- and D-DNA models are almost equally stable. Hence, we conclude that the right- and left-handed double-helical models of poly[d(I-C)] in a given form (B or D) are equally likely and that the fiber diffraction data do not permit discrimination.

A reply to a discussion by D.J. Cook of the paper a reaction product of lime and silica from rice husk asha star, open

Abstract is not available.

Sequence-dependent conformation of an A-DNA double helix: The crystal structure of the octamer d(G-G-T-A-T-A-C-C)

The crystal structures of the synthetic self-complementary octamer d(G-G-T-A-T-A-C-C) and its 5-bromouracil-containing analogue have been refined to R values of 20% and 14% at resolutions of 1·8 and 2·25 Å, respectively. The molecules adopt an A-DNA type double-helical conformation, which is minimally affected by crystal forces. A detailed analysis of the structure shows a considerable influence of the nucleotide sequence on the base-pair stacking patterns. In particular, the electrostatic stacking interactions between adjacent guanine and thymine bases produce symmetric bending of the double helix and a major-groove widening. The sugar-phosphate backbone appears to be only slightly affected by the base sequence. The local variations in the base-pair orientation are brought about by correlated adjustments in the backbone torsion angles and the glycosidic orientation. Sequence-dependent conformational variations of the type observed here may contribute to the specificity of certain protein-DNA interactions.

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 +/- 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 +/- 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 +/- 0.06 s.e.), and ADHD and major depressive disorder (0.32 +/- 0.07 s.e.), low between schizophrenia and ASD (0.16 +/- 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

Ambassador von Staden and Secretary Califano signing the U.S.-German Social Security Agreement; Washington, D.C.

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Free Range Hens Use the Range More When the Outdoor Environment Is Enriched.

To evaluate the role of using forage, shade and shelterbelts in attracting birds into the range, three trials were undertaken with free range layers both on a research facility and on commercial farms. Each of the trials on the free range research facility in South Australia used a total of 120 laying hens (Hyline Brown). Birds were housed in an eco-shelter which had 6 internal pens of equal size with a free range area adjoining the shelter. The on-farm trials were undertaken on commercial free range layer farms in the Darling Downs in Southeast Queensland with bird numbers on farms ranging from 2,000-6,800 hens. The first research trial examined the role of shaded areas in the range; the second trial examined the role of forage and the third trial examined the influence of shelterbelts in the range. These treatments were compared to a free range area with no enrichment. Aggressive feather pecking was only observed on a few occasions in all of the trials due to the low bird numbers housed. Enriching the free range environment attracted more birds into the range. Shaded areas were used by 18% of the hens with a tendency (p = 0.07) for more hens to be in the paddock. When forage was provided in paddocks more control birds (55%) were observed in the range in morning than in the afternoon (30%) while for the forage treatments 45% of the birds were in the range both during the morning and afternoon. When shelterbelts were provided there was a significantly (p<0.05) higher % of birds in the range (43% vs. 24%) and greater numbers of birds were observed in areas further away from the poultry house. The results from the on-farm trials mirrored the research trials. Overall 3 times more hens used the shaded areas than the non shaded areas, with slightly more using the shade in the morning than in the afternoon. As the environmental temperature increased the number of birds using the outdoor shade also increased. Overall 17 times more hens used the shelterbelt areas than the control areas, with slightly more using the shelterbelts in the afternoon than in the morning. Approximately 17 times more birds used the forage areas compared to the control area in the corresponding range. There were 8 times more birds using a hay bale enriched area compared to the area with no hay bales. The use of forage sources (including hay bales) were the most successful method on-farm to attract birds into the range followed by shelterbelts and artificial shade. Free range egg farmers are encouraged to provide pasture, shaded areas and shelterbelts to attract birds into the free range.

Studies on follicular atresia: role of tropic hormone and steroids in regulating cathepsin-D activity of preantral follicles of the immature rat

The ovary of the immature female rat is comprised of primary and medium-sized preantral follicles. Upon stimulation with FSH or PMSG, the cathepsin-D activity, a representative lysosomal enzyme of granulosa cells, is reduced by 50% (P < 0.01). 17β-Estradiol at the doses tried was unable to mimic this effect. Blockade of steroidogenesis with cyanoketone also had no effect on the cathepsin-D activity of isolated granulosa cells. Dihydrotestosterone (DHT), however, at a dose of 1 mg/rat was able to inhibit PMSG's tropic action. It brought about an increase in cathepsin-D activity and reduction in steroidogenic activity of isolated granulosa cells. The atretogenic activity of DHT could be relieved by supplementation with exogenous FSH. DHT was observed to significantly reduce (P < 0.01) endogenous FSH and LH levels within 12–18 h of its injection suggesting that its atretic effect was due to its action at the pituitary rather than the gonad. In addition to the above the ability of 15 IU of PMSG to reduce cathepsin-D activity of granulosa cells was also significantly reduced (P < 0.01) if endogenous FSH was neutralized by a specific FSH antiserum. The present study suggests that as far as small and medium-sized primary and preantral follicles are concerned, FSH lack is the essential signal for onset of atresia.

Synthesis, Reactivity and Biological Activity of 17β-HSD1 Inhibitors Based on a Thieno[2,3-d]pryrimidin-4(3H)-one Core

Breast cancer is the most common cancer in women in Western countries. In the early stages of development most breast cancers are hormone-dependent, and estrogens, especially estradiol, have a pivotal role in their development and progression. One approach to the treatment of hormone-dependent breast cancers is to block the formation of the active estrogens by inhibiting the action of the steroid metabolising enzymes. 17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is a key enzyme in the biosynthesis of estradiol, the most potent female sex hormone. The 17beta-HSD1 enzyme catalyses the final step and converts estrone into the biologically active estradiol. Blocking 17beta-HSD1 activity with a specific enzyme inhibitor could provide a means to reduce circulating and tumour estradiol levels and thus promote tumour regression. In recent years 17beta-HSD1 has been recognised as an important drug target. Some inhibitors of 17beta-HSD1 have been reported, however, there are no inhibitors on the market nor have clinical trials been announced. The majority of known 17beta-HSD1 inhibitors are based on steroidal structures, while relatively little has been reported on non-steroidal inhibitors. As compared with 17beta-HSD1 inhibitors based on steroidal structures, non-steroidal compounds could have advantages of synthetic accessibility, drug-likeness, selectivity and non-estrogenicity. This study describes the synthesis of large group of novel 17beta-HSD1 inhibitors based on a non-steroidal thieno[2,3-d]pyrimidin-4(3H)-one core. An efficient synthesis route was developed for the lead compound and subsequently employed in the synthesis of thieno[2,3-d]pyrimidin-4(3H)-one based molecule library. The biological activities and binding of these inhibitors to 17beta-HSD1 and, finally, the quantitative structure activity relationship (QSAR) model are also reported. In this study, several potent and selective 17beta-HSD1 inhibitors without estrogenic activity were identified. This establishment of a novel class of inhibitors is a progressive achievement in 17beta-HSD1 inhibitor development. Furthermore, the 3D-QSAR model, constructed on the basis of this study, offers a powerful tool for future 17beta-HSD1 inhibitor development. As part of the fundamental science underpinning this research, the chemical reactivity of fused (di)cycloalkeno thieno[2,3-d]pyrimidin-4(3H)-ones with electrophilic reagents, i.e. Vilsmeier reagent and dimethylformamide dimethylacetal, was investigated. These findings resulted in a revision of the reaction mechanism of Vilsmeier haloformylation and further contributed to understanding the chemical reactivity of this compound class. This study revealed that the reactivity is dependent upon a stereoelectronic effect arising from different ring conformations.

Crusted scabies is associated with increased IL-17 secretion by skin T cells

Scabies is an ectoparasitic infestation by the mite Sarcoptes scabiei. Although commonly self-limiting, a fraction of patients develop severely debilitating crusted scabies. The immune mechanisms underlying the development of crusted scabies are unclear, and undertaking longitudinal infection studies in humans is difficult. We utilized a porcine model to compare cellular immune responses in peripheral blood and skin of pigs with different clinical manifestations of scabies (n = 12), and in uninfected controls (n = 6). Although clinical symptoms were not evident until at least 4 weeks post-infestation, the numbers of peripheral IFNγ-secreting CD4+ T cells and γδ T cells increased in infected pigs from week 1 post-infestation. γδ T cells remained increased in the blood at week 15 post-infestation. At week 15, skin cell infiltrates from pigs with crusted scabies had significantly higher CD8+ T cell, γδ T cell and IL-17+ cell numbers than those with ordinary scabies. Peripheral IL-17 levels were not increased, suggesting that localized skin IL-17-secreting T cells may play a critical role in the pathogenesis of crusted scabies development. Given the potential of anti-IL-17 immunotherapy demonstrated for other inflammatory skin diseases, this study may provide a novel therapeutic avenue for patients with recurrent crusted scabies.

Gas-crystal photoreaction: the structures of 4,4'-dimethoxy(thiobenzophenone) (I), C15H14O2S, and 4,4'-bis(dimethylamino)thiobenzophenone (II), C17H20N2S

(I): M r = 258.34, triclinic, Pi, a = 9.810 (3), b=9.635(3), e=15.015(4)A, a=79.11(2), #= 102.38 (3), y = 107.76 (3) o, V= 1308.5 A 3, Z = 4, Din= 1.318 (3) (by flotation in KI solution), D x = 1.311 g cm -3, Cu Ka, 2 = 1.5418/~, g = 20-05 cm -1, F(000) = 544, T---- 293 K, R = 0.074 for 2663 reflections. (II): M r = 284.43, monoclinic, P2~/c, a= 17.029 (5), b=6.706 (5), c= 14.629 (4), t= 113.55 (2) ° , V=1531.4A 3, Z=4, Dm=1.230(5) (by flotation in KI solution), Dx= 1.234gem -3, Mo Ka, 2 = 0.7107 A, g = 1.63 cm-1; F(000) = 608, T= 293 K, R = 0.062 for 855 reflections. The orientation of the C=S chromophores in the crystal lattice and their reactivity in the crystalline state are discussed. The C--S bonds are much shorter than the normal bond length [1.605 (4) (I), 1.665 (8) A (II) cf. 1.71 A].

J.D.C. settlements in Kherson region

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Plan zemelʻnogo uchastka poselka Kalininfelʻd N 17 Leninskogo fonda

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Vapor phase oxidation of ethanol over thorium molybdate catalyst

Ethanol oxidation in the vapor phase was studied in an isothermal flow reactor using thorium molybdate catalyst in the temperature range 220–280 °C. Under these conditions the catalyst was highly selective to acetaldehyde formation. The rate data were well represented by a steady state two-stage redox model given by the equation: View the MathML source The parameters of the above model were estimated by linear and nonlinear least squares methods. In the case of nonlinear estimation the sum of the squares of residuals decreased. The activation energies and preexponential factors for the reduction and oxidation steps of the model, estimated by nonlinear least squares technique are: 9.47 kcal/mole, 9.31 g mole/ (sec) (g cat) (atm) and 9.85 kcal/mole, 0.17 g mole/(sec) (g cat) (atm)0.5, respectively. Oxidations of ethanol and methanol over thorium molybdate catalyst were compared under similar conditions.

D.c. and a.c. polarographic behaviour of vanadium-glycine complexes

A detailed investigation of the d.c. polarographic behaviour of vanadium(V),-(IV) and -(III) in glycine solutions has been made keeping the total glycine concentration at 0.1, 0.5 and 1.0 M and varying the pH of the solution. Experiments keeping the pH constant (using different ratios of glycine and glycine anion) and varying the glycine anion concentration, and also in predominantly anion solutions, have been made.