Effect of cisplatin and c-myb antisense phosphorothioate oligodeoxynucleotides combination on a human colon carcinoma cell line in vitro and in vivo

We investigated the effect of c-myb antisense phosphorothioate oligodeoxynucleotides [(S)ODNs] and cisplatin (CDDP) combination on the human colon carcinoma cell line LoVo Dx both in vitro and in nude mice bearing LoVo Dx solid tumour. We show that antisense (S)ODN treatment decreases c-myb mRNA and protein expression, induces growth arrest in the G1 phase of the cell cycle, and inhibits cell proliferation. In vivo treatment with c-myb antisense (S)ODNs results in a reduction in tumour growth. A greater inhibition of cell proliferation in vitro and a higher increase of tumour growth inhibition and growth delay in vivo were obtained with the combination of (S)ODNs and CDDP than when the two agents were administered separately. This comparative study, using the same tumour cell line in vitro and in vivo, suggests that c-myb antisense (S)ODNs might be useful in the therapy of colon cancer in combination with antineoplastic drugs.     

Preparation and structural study of Mg<Subscript>1−<Emphasis Type="Italic">x</Emphasis></Subscript>Zn<Subscript><Emphasis Type="Italic">x</Emphasis></Subscript>TiO<Subscript>3</Subscript> ceramics and their dielectric properties from 1 Hz to 7.7 GHz

A series of Mg_1?x Zn _x TiO₃, x = 0–0.5 (MZT0–MZT0.5) ceramics was synthesised and characterised. The dielectric properties of the samples in the frequency range of 1 Hz–7.7 GHz were explored using three different methods: a contacting electrode method, a parallel-plate method and a perturbed resonator method. The electrical properties in the space charge and dipolar polarisation frequency ranges are discussed in relation to the phase composition and microstructure data. Differences in the zinc substitution divided the dielectrics into two groups, namely MZT0–MZT0.2 and MZT0.3–MZT0.5, each with different amount of a main Mg_1?x Zn _x TiO₃ solid solution phase and a secondary solid solution phase. Zinc substitution promoted the density of the ceramics, improved the purity of the main phase and increased the permittivity for frequencies up to 10⁸ Hz, but reduced the permittivity in the microwave range. In the MZT0.3–MZT0.5 samples, for frequencies less than 1 MHz the quality (Q × f) factors were lower and log σ _a.c, the AC conductivity, was higher than for the MZT0–MZT0.2 samples. Above 10 MHz, the (Q × f) factors and log σ _a.c of the two groups were similar.     

An Overview of Synergistic Data Tools for Biological Scrutiny

A network of biological databases is reviewed, supplying a framework for studies of human genes and the association of their genomic variations with human phenotypes. The network is composed of GeneCards, the human gene compendium, which provides comprehensive information on all known and predicted human genes, along with its suite members GeneDecks and GeneLoc. Two databases are shown that address genes and variations focusing on olfactory reception (HORDE) and transduction (GOSdb). In the realm of disease scrutiny, we portray MalaCards, a novel comprehensive database of human diseases and their annotations. Also shown is GeneKid, a tool aimed at generating novel kidney disease biomarkers using systems biology, as well as Xome, a database for whole-exome next-generation DNA sequences for human diseases in the Israeli population. Finally, we show LifeMap Discovery, a database of embryonic development, stem cell research and regenerative medicine, which links to both GeneCards and MalaCards.     

Deep Resequencing of 9 Candidate Genes Identifies a Role for ARAP1 and IGF2BP2 in Modulating Insulin Secretion Adjusted for Insulin Resistance in Obese Southern Europeans

Type 2 diabetes is characterized by impairment in insulin secretion, with an established genetic contribution. We aimed to evaluate common and low-frequency (1–5%) variants in nine genes strongly associated with insulin secretion by targeted sequencing in subjects selected from the extremes of insulin release measured by the disposition index. Collapsing data by gene and/or function, the association between disposition index and nonsense variants were significant, also after adjustment for confounding factors (OR = 0.25, 95% CI = 0.11–0.59, p = 0.001). Evaluating variants individually, three novel variants in ARAP1, IGF2BP2 and GCK, out of eight reaching significance singularly, remained associated after adjustment. Constructing a genetic risk model combining the effects of the three variants, only carriers of the ARAP1 and IGF2BP2 variants were significantly associated with a reduced probability to be in the lower, worst, extreme of insulin secretion (OR = 0.223, 95% CI = 0.105–0.473, p < 0.001). Observing a high number of normal glucose tolerance between carriers, a regression posthoc analysis was performed. Carriers of genetic risk model variants had higher probability to be normoglycemic, also after adjustment (OR = 2.411, 95% CI = 1.136–5.116, p = 0.022). Thus, in our southern European cohort, nonsense variants in all nine candidate genes showed association with better insulin secretion adjusted for insulin resistance, and we established the role of ARAP1 and IGF2BP2 in modulating insulin secretion.     

Dinkel und Z:oliakie

Zusammenfassung Über Dinkel (Triticum spelta L.) liegen bezüglich sciner Wirkung auf Zöliakiekranke keine Untersuchungen vor. Da eine klinische Testung aus ethischen Gründen nicht in Betracht kommt, wurden Dinkel und Weichweizen (Triticum aestivum L.) in den für die Zöliakieauslösung relevanten N-terminalen Sequenzen der -Gliadine verglichen. Dazu wurden die Gliadinfraktionen der Dinkelsorten Roquin und Schwabenkorn sowie der Weichweizensorte Rektor durch RP-HPLC präparativ getrennt und dominierende -Gliadine N-terminal sequenziert. Innerhalb der ersten 25 Positionen war kein signifikanter Unterschied zwischen den Dinkel- und Weichweizensorten zu erkennen. Zur Erfassung der vom N-Terminus weiter entfernt liegenden Sequenzabschnitte wurden die Gliadinfraktionen der Dinkelsorten mit Pepsin und Trypsin hydrolysiert. Die Partialhydrolysate wurden nacheinander durch Gelpermeationschromatographie und RP-HPLC aufgetrennt. Die aus dem N-terminalen Bereich von -Gliadinen stammenden Peptide wurden mit Hilfe von Referenzpeptiden identifiziert, die in einer früheren Arbeit [diese Zeitschrift 194 229 (1992)] aus einem Gliadinhydrolysat von Weichweizen isoliert wurden. Übereinstimmende Retentionszeiten bei der HPLC und Aminosäurezusammensetzungen der entsprechenden Peptide weisen darauf hin, daß auch in einem längeren N-terminalen Abschnitt (Positionen 3–56) der -Gliadine von Dinkel und Weichweizen identische Sequenzen vorliegen. Es muß daher davon ausgegangen werden, daß auch Dinkel Zöliakie auslöst und von Zöliakiekranken gemieden werden muß.

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Spelt wheat and coeliac disease

Spelt wheat (Triticum spelta L.) has not been investigated for the toxicity on coeliac disease patients until now. Because clinical studies are out of considerations for ethical reasons, spelt wheat and coeliac-active bread wheat (Triticum aestivum L.) were compared by the analysis of N-terminal sequences of -gliadins, which have been proposed to be responsible for the toxic effect. The gliadin fractions of the spelt wheats Roquin and Schwabenkorn and of the bread wheat Rektor were preparatively separated by RP-HPLC and major -gliadin components were then compared by N-terminal sequence analysis. The results did not reveal any significant difference between spelt and bread wheats within the first 25 positions. For the determination of sequences further from the N-terminus, the gliadin fractions of the spelt wheats were hydrolyzed with pepsin and trypsin. The resulting peptides were successively separated by gel permeation chromatography and RP-HPLC. Those peptides derived from the N-terminal part of -gliadins were identified by reference peptides isolated previously from bread wheat [this journal 194: 229 (1992)]. Retention times upon RP-HPLC and amino acid compositions of corresponding peptides confirmed the identity of spelt and bread wheat concerning the N-terminal sequences of -gliadins from position 3 to 56. For these reasons, it can be concluded that spelt wheat is a coeliac-toxic cereal and has to be avoided by coeliac patients.

     

Phytate-calcium interactions with soy protein

Solubilities of mixtures of soy protein isolate, calcium and phytate were determined as a function of pH and molar ratio of the components. Below the isoelectric point, phytate and protein solubility profiles paralleled each other, indicating some type of protein-phytate interaction. Addition of phytate shifted the isoelectric point and the minimum solubility to lower values. Between the isoelectric point and pH 6.5, the complex apparently dissociates; addition of phytate results in an increase in the maximum solubility of the phosphorus and the protein, as well as a shift in their solubility profiles. Calcium has no apparent effect on protein solubility in this pH region. Higher pH (>6.5) results in the formation of ternary protein-calcium-phytate complexes and a significant drop in calcium and phosphorus solubility, probably due to formation of insoluble calcium phytate salts.     

A unified mathematical programming formulation of strain driven and interior point algorithms for shakedown and limit analysis

A mathematical programming formulation of strain‐driven path‐following strategies to perform shakedown and limit analysis for perfectly elastoplastic materials in an FEM context is presented. From the optimization point of view, standard arc‐length strain‐driven elastoplastic analyses, recently extended to shakedown, are identified as particular decomposition strategies used to solve a proximal point algorithm applied to the static shakedown theorem that is then solved by means of a convergent sequence of safe states. The mathematical programming approach allows: a direct comparison with other non‐linear programming methods, simpler convergence proofs and duality to be exploited. Owing to the unified approach in terms of total stresses, the strain‐driven algorithms become more effective and less non‐linear with respect to a self‐equilibrated stress formulation and easier to implement in the existing codes performing elastoplastic analysis. The elastic domain is represented avoiding any linearization of the yield function so improving both the accuracy and the performance. Better results are obtained using two different finite elements, one with a good behavior in the elastic range and the other suitable for performing elastoplastic analysis. The proposed formulation is compared with a specialized implementation of the primal–dual interior point method suitable to solve the problems at hand. Copyright © 2011 John Wiley & Sons, Ltd.