Direct observation of cations and polynucleotides explains polyion adsorption to like-charged surfaces

We show an experimental approach for directly observing the condensation of polynucleotides and their electrolyte counterions at a liquid/solid interface. X-ray standing waves (XSW) generated by Bragg diffraction from a d = 20 nm Si/Mo multilayer substrate are used to measure the distinct distribution profiles of the polyanions and simple cations along the surface normal direction with subnanometer resolution. The 1D spatial sensitivity of this approach is enhanced by observing the XSW induced fluorescence modulations over multiple orders of Bragg peaks. We study the interesting divalent cation driven adsorption of anionic polynucleotides to anionic surfaces by exposing a hydroxyl-terminated silica surface to an aqueous solution with ZnCl2 and mercurated poly-uridylic acid (a synthetic RNA molecule). The in situ long-period XSW measurements are used to follow the evolution of both the Zn and Hg distribution profiles during the adsorption process. The conditions and physical mechanisms that govern the observed divalent cation adsorption and subsequent polynucleotide adsorption to an anionic surface are explained by a thermodynamic model that incorporates nonlinear electrostatic effects.     

Cobalt-mediated approach for the synthesis of terpene-based hybrids

[structure: see text] Dicobalt-beta-pinene hybrids of types I and II have been prepared using a Nicholas reaction between propargyl derivatives, obtained from commercial (1R)-(-)-myrtenal, and different aromatic nucleophiles. The method is suitable for the preparation of densely functionalized bio-organometallic natural product-based hybrids, as demonstrated by the preparation of a beta-pinene-neoclerodane hybrid.     

UVA exposure affects UVB and cis-urocanic acid-induced systemic suppression of immune responses in Listeria monocytogenes-infected Balb/c mice

Ultraviolet radiation can inhibit immune responses locally as well as systemically. Such effects have been measured in animals and humans exposed to ultraviolet B (wavelength 280-315 nm) (UVB) and ultraviolet A (315-400 nm) (UVA). The precise wavelength dependence is important for the identification of possible molecular targets and for assessments of risk of different artificial UV sources and solar UV. In such analyses, it is commonly assumed that radiation energy from each wavelength contributes to the effect independent of the other wavelengths. Here we show that this assumption does not hold good. In the present study, it was investigated whether exposure to broadband UVA or longwave ultraviolet A 1 (340-400 nm) (UVA 1) prior to the standard immunosuppressive UVB protocol might modulate the immunosuppressive effects induced by UVB. Preexposure to broadband UVA or longwave UVA 1, 1 day prior to the standard immunosuppressive UVB protocol, inhibited the UVB-induced suppression of delayed type hypersensitivity (DTH) to Listeria monocytogenes significantly. This effect was not associated with restoring the number of interleukin (IL-12)-positive cells in the spleen. Since isomerization of trans-urocanic acid (UCA) into the immunosuppressive cis-UCA isomer plays a crucial role in UVB-induced immunomodulation, in a second set of experiments it was investigated whether immunosuppression induced by cis-UCA might also be downregulated by preexposure to UVA. Animals were exposed to broad-band UVA or longwave UVA 1 prior to application of an immunosuppressive dose of cis- or trans-UCA as a control. Both UVA and UVA 1 appear to inhibit the cis-UCA-induced systemic immunosuppression (DTH and IL-12) to L. monocytogenes. These studies clearly show that UVA radiation modulates both UVB and cis-UCA-induced immunomodulation. In general, our studies indicate that both broadband UVA and longwave UVA 1 could induce modulation of UVB and cis-UCA-induced immunomodulation. As sunlight contains both UVA and UVB radiation the balance between these two radiations apparently determines the net immunomodulatory effect.     

Virtual darwinian drug design: QSAR inverse problem, virtual combinatorial chemistry, and computational screening

The generation of diversity and its further selection by an external system is a common mechanism for the evolution of the living species and for the current drug design methods. This assumption allows us to label the methods based on generation and selection of molecular diversity as "Darwinian" ones, and to distinguish them from the structure-based, structure-modulation approaches. An example of a Darwinian method is the inverse QSAR. It consists of the computational generation of candidate chemical structures and their selection according to a previously established QSAR model. New trends in the field of combinatorial chemical syntheses comprise the concepts of virtual combinatorial synthesis and virtual or computational screening. Virtual combinatorial synthesis, closely related to inverse QSAR, can be defined as the computational simulation of the generation of new chemical structures by using a combinatorial strategy to generate a virtual library. Virtual screening is the selection of chemical structures having potential desirable properties from a database or virtual library in order to be synthesized and assayed. This review is mainly focused on graph theoretical drug design approaches, but a survey with key references is provided that covers other simulation methods.     

Separation of proteins with a molecular mass difference of 2 kDa utilizing preparative double-inverted gradient polyacrylamide gel electrophoresis under nonreducing conditions: application to the isolation of 24 kDa human growth hormone

A method for separating proteins with a molecular mass difference of 2 kDa using SDS-PAGE under nonreducing conditions is presented. A sample mixture containing several human growth hormone (hGH) isoforms was initially separated on a weak anion-exchange column. Fractions rich in 24 kDa hGH as determined by analytical SDS-PAGE were pooled and further separated by cation-exchange chromatography. The fractions pooled from the cation-exchange chromatography contained two hGH isoforms with a 2 kDa molecular mass difference according to SDS-PAGE analysis, 22 and 24 kDa hGH. The 22 and 24 kDa hGH were separated using continuous-elution preparative double-inverted gradient PAGE (PDG-PAGE) under nonreducing conditions. The preparative electrophoresis gel was composed of three stacked tubular polyacrylamide matrices, a 4% stacking gel, a 13-18% linear gradient gel, and a 15-10% linear inverted gradient gel. Fractions containing purified 24 kDa hGH were pooled and Western blot analysis displayed immunoreactivity to antihGH antibodies. PDG-PAGE provides researchers with an electrophoretic technique to preparatively purify proteins under nonreducing conditions with molecular mass differences of 2 kDa.     

Thermal decomposition of some imidazole and N-methyl substituted imidazole complexes of palladium(II)

We describe in this paper the thermal decomposition in air of several complexes of palladium(II) chloride with imidazole and N-methylimidazole. Although the final process of the decomposition gives (PdCl₂)_n which then decomposes to pa ladium which oxidizes to PdO, there are interesting differences in the initial decomposition path. The reasons for these differences appear to be related to the trans-effect and to the presence in the imidazole complexes of hydrogen bonds which break down at temperatures of around 220.

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Zusammenfassung In diesem Beitrag wird die thermische Zersetzung verschiedener Komplexe des Palladium(II)chlorids mit Imidazol und N-Methylimidazol in Luft beschrieben. Obwohl der Endvorgang der Zersetzung (PdCl₂)_n ergibt, welches dann zu Palladium zersetzt und zu PdO oxidiert wird, bestehen interessante Unterschiede im Anfangsschritt der Zersetzung. Die Ursachen dieser Unterschiede scheinen mit dem Trans-Effekt und der Anwesenheit von Wasserstoffbindungen in den Imidazolkomplexen verbunden zu sein, welche bei Temperaturen um 220 zerstört werden.

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Résumé La décomposition thermique dans l'air de plusieurs complexes du chlorure de palladium(II) avec l'imidazole et le méthyl-4-imidazole est décrite. Bien que l'étape finale de la décomposition donne (PdCl₂)_n qui se décompose ensuite en palladium qui s'oxyde en PdO, des différences intéressantes apparaissent dans les étapes initiales de la décomposition. Les causes de ces différences sont en rapport avec l'effet trans et la présence, dans les complexes avec l'imidazole, de liaisons hydrogÊne qui se rompent vers 220.

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(II) -. (PdCl₂)_n, , PdO, . , - , 220.

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One of us (M.C. Navarro Ranninger) would like to thank the D.G.E.S.I. for a grant that allowed her to work on this research.     

The complexation of Cr(III) and Cr(VI) with flavones in micellar media and its use for the spectrophotometric determination of chromium

The complexation of chromium by different flavonoid dyes in micellar media has been studied, in particular the reaction between chromium and quercetin. Micellar effects, the reaction pathway proposed and the application of the method to the determination of Cr(VI) and Cr(VI) + Cr(III) mixtures are discussed.     

Chromatographic characterization of adult and foetal rat insulin

Foetal rat pancreatic rudiments explanted on day 14 of gestation were grown in organ culture in medium enriched with amino acids. The size of the insulin granules was increased, resulting in an insulin granule volume fraction greater than the volume fraction measured in pancreas grown in vivo. The pancreas was extracted and the insulin compared. Serial dilution curves of extracts of adult pancreas and pancreas grown in vitro are parallel in the insulin radioimmunoassay, whereas extracts of pancreas of foetus developing in utero appear immunologically different. Adult and foetal rat insulin (in utero) were purified using chromatography on OPTI UP C12, cellulose thin-layer chromatography plates, cellulose acetate foil electrophoresis and finally high-performance liquid chromatography. The ratio of insulin I to insulin II was found to be 1.5 for the adult and 2.7 for the foetus. These results show that there is an unequal expression of the two non-allelic genes controlling insulin biosynthesis in foetal and adult rat pancreas.     

The effects of different dietary fiber pectin structures on the gastrointestinal immune barrier: impact via gut microbiota and direct effects on immune cells

Pectins are dietary fibers with different structural characteristics. Specific pectin structures can influence the gastrointestinal immune barrier by directly interacting with immune cells or by impacting the intestinal microbiota. The impact of pectin strongly depends on the specific structural characteristics of pectin; for example, the degree of methyl-esterification, acetylation and rhamnogalacturonan I or rhamnogalacturonan II neutral side chains. Here, we review the interactions of specific pectin structures with the gastrointestinal immune barrier. The effects of pectin include strengthening the mucus layer, enhancing epithelial integrity, and activating or inhibiting dendritic cell and macrophage responses. The direct interaction of pectins with the gastrointestinal immune barrier may be governed through pattern recognition receptors, such as Toll-like receptors 2 and 4 or Galectin-3. In addition, specific pectins can stimulate the diversity and abundance of beneficial microbial communities. Furthermore, the gastrointestinal immune barrier may be enhanced by short-chain fatty acids. Moreover, pectins can enhance the intestinal immune barrier by favoring the adhesion of commensal bacteria and inhibiting the adhesion of pathogens to epithelial cells. Current data illustrate that pectin may be a powerful dietary fiber to manage and prevent several inflammatory conditions, but additional human studies with pectin molecules with well-defined structures are urgently needed.Subject terms: Mucosal immunology, Translational immunology     

Enantioselective total syntheses of belactosin A, belactosin C, and its homoanalogue

[reaction: see text] Enantioselective total syntheses of belactosin A, belactosin C, and its homoanalogue have been accomplished in high overall yields (32% for belactosin A from the amino acid 10, and 35 and 36% for belactosin C and its homoanalogue, respectively). This concise approach comprises a novel sequential acylation/beta-lactonization reaction and allows a facile alteration of the substituents, thus providing a flexible route to a new family of highly active belactosin-based proteasome inhibitors.