Sulfated Derivatives of Arabinogalactan and Their Anticoagulant Activity

Russian Journal of Bioorganic Chemistry - A comparison of IR spectra and molecular weight distribution of arabinogalactan sulfates as sodium and ammonium salts obtained using various sulfating...     

Lipophilic prodrugs of a triazole-containing colchicine analogue in liposomes: Biological effects on human tumor cells

Colchicine site binders—blockers of tubulin polymerization—are potential antimitotic agents for anticancer therapy. To reduce their systemic toxicity and improve biodistribution, encapsulation in nanosized liposomes may be employed. Liposomes present a convenient means for preparation of injectable for-mulations of hydrophobic compounds, however colchicine as such is known to leak through the lipid bilayer. In this study, newly synthesized triazole-containing analogues of colchicine and allocolchicine, and their palmitic and oleic esters (lipophilic prodrugs) were tested for anti-proliferative activity and apoptosis-inducing potential. In contrast to colchicine conjugates, whose activities ranged with those of colchicine, allocolchicine derivatives exhibited drastically lower effects and were discarded. Liposomes of about 100 nm in diameter composed of egg phosphatidylcholine-yeast phosphatidylinositol-palmitic or oleic prodrug, 8: 1: 1, by mol, were prepared by standard extrusion technique and tested in a panel of four human tumor cell lines. Liposome formulations preserved the biological activities of the parent colchicinoid the most towards human epithelial tumor cells. Moreover, liposomal form of the oleoyl bearing colchicinoid inhibited cell proliferation more efficiently than free lipophilic prodrug. Due to substantial loading capacity of the liposomes, the dispersions contain sufficient concentration of the active agent to test wide dose range in experiments on systemic administration to animals.     

Abnormal mitosis triggers p53-dependent cell cycle arrest in human tetraploid cells

Erroneously arising tetraploid mammalian cells are chromosomally instable and may facilitate cell transformation. An increasing body of evidence shows that the propagation of mammalian tetraploid cells is limited by a p53-dependent arrest. The trigger of this arrest has not been identified so far. Here we show by live cell imaging of tetraploid cells generated by an induced cytokinesis failure that most tetraploids arrest and die in a p53-dependent manner after the first tetraploid mitosis. Furthermore, we found that the main trigger is a mitotic defect, in particular, chromosome missegregation during bipolar mitosis or spindle multipolarity. Both a transient multipolar spindle followed by efficient clustering in anaphase as well as a multipolar spindle followed by multipolar mitosis inhibited subsequent proliferation to a similar degree. We found that the tetraploid cells did not accumulate double-strand breaks that could cause the cell cycle arrest after tetraploid mitosis. In contrast, tetraploid cells showed increased levels of oxidative DNA damage coinciding with the p53 activation. To further elucidate the pathways involved in the proliferation control of tetraploid cells, we knocked down specific kinases that had been previously linked to the cell cycle arrest and p53 phosphorylation. Our results suggest that the checkpoint kinase ATM phosphorylates p53 in tetraploid cells after abnormal mitosis and thus contributes to proliferation control of human aberrantly arising tetraploids.     

Structural and functional characteristics of various forms of red pigment of yeast Saccharomyces cerevisiae and its synthetic analog

Structural and functional characteristics of the yeast red pigment (product of polymerization of N¹-(β-D-ribofuranosyl)-5-aminoimidazole), isolated from ade1 mutant cells of Saccharomyces cerevisiae and its deribosylated derivatives (obtained by acid hydrolysis) and its synthetic pigment analogue (product of polymerization of N¹-methyl-5-aminoimidazole in vitro) were obtained. Products of in vitro polymerization were identified using mass spectrometry. The ability of these pigments to inhibit amyloid formation using insulin fibrils was compared. All the studied compounds are able to interact with amyloids and inhibit their growth. Electron and atomic force microscopy revealed a common feature inherent in the insulin fibrils formed in the presence of these compounds—they are merged into conglomerates more stable and resistant to the effects of ultrasound than are insulin aggregates grown without pigments. We suggest that all these compounds can cause coalescence of fibrils partially blocking the loose ends and, thereby, inhibit attachment of monomers and formation of new fibrils.     

Somatoform disorders among patients attending walk-in clinics in Trinidad: prevalence and association with depression and anxiety

Objectives Somatoform disorders are common in international primary care settings, but have been little studied in the developing world. The objective of this study was to determine the prevalence of severe undifferentiated somatoform disorder, and its relationship to depression and anxiety, among patients attending walk-in clinics in Trinidad.Methods The study participants, who were all aged 18 years or older and attending walk-in clinics at 16 randomly selected health centres, were surveyed between May and August 2007 using the PRIME-MD questionnaire.Results There were 594 participants (the response rate was 92%), of whom 72.7% were female. Their ages ranged from 18 to 93 years, and 54.5% were over 50 years of age. In total, 37.2% were married and 25.9% were single. Indo-Trinidadians represented 43.1% and Afro-Trinidadians represented 36% of the study sample; 56.5% of the participants reported that their income was less than US$ 400 per month, and 65.7% were unemployed. At walk-in clinics in Trinidad, the estimated prevalence of severe undifferentiated somatoform disorder was 10.3% (95% CI: 7.86–12.74), that of hypochondriasis was 28.5% (95% CI: 24.9–32.1), and that of body dysmorphic disorder was 15.8% (95% CI: 11.9–18.7). Severe undifferentiated somatoform disorder was statistically significantly associated with gender and ethnicity but not with age, level of education, employment status or income. Chi-square testing found significant associations between the presence of severe undifferentiated somatoform disorder and both depression and anxiety (P < 0.05), between hypochondriasis and both anxiety and depression (P < 0.05), and between body dysmorphic disorder and depression (P < 0.05) but not anxiety. Regression analysis suggested that the demographic features that predicted severe undifferentiated somatoform disorder were being female or Indo-Trinidadian.Conclusions Walk-in clinics in Trinidad that serve older patients on a lower income have a high proportion of patients with somatoform disorders as measured by the PRIME-MD scale. These patients exhibit many features of anxiety and depression. These findings have implications for medical training and service delivery.     

Comparative Analysis of Nucleotide Fluorescent Analogs for Registration of DNA Conformational Changes Induced by Interaction with Formamidopyrimidine-DNA Glycosylase Fpg

Russian Journal of Bioorganic Chemistry - DNA-substrates containing fluorescent DNA base analogs are widely used to study protein–nucleic acid interactions. In the case of DNA-recognizing...     

Adaptations of Malus domestica Borkh. (Rosaceae) Fruits Grown at Different Altitudes

Russian Journal of Plant Physiology - Cytophysiological adaptive features of apple fruits (Malus domestica Borkh.) were examined as a function of growth altitude—300, 500, 700, and 1200 m...     

Effects of pH on structural and functional properties of porin from the outer membrane of <Emphasis Type="Italic">Yersinia pseudotuberculosis</Emphasis>. I. Functionally important conformational transitions of yersinin

The changes in the structural and functional properties of yersinin, a porin from the outer membrane of Yersinia pseudotuberculosis, were studied in the pH range 8.0–2.0 using SDs-PAGE, scanning microcalorimetry, optical spectroscopy and bilayer lipid membrane technique. It was found that in the pH range under study the changes in the spatial structure of yersinin were biphasic. In the first steps of pH titration (pH 8.0–4.5), porin underwent a series of conformational transitions, which did not affect the trimeric structure of its molecule. In the second step (pH 4.0–2.0), structural rearrangements led to dissociation of the protein trimers into monomers. It is noteworthy that complete unfolding of the polypeptide chain of the protein was not observed even at low values of pH. Thus, at pH 2.0 the conformational intermediate of the protein retained up to 50% of its regular secondary structure. Studies of current fluctuations in the bilayer lipid membrane revealed that in weakly acidic media the conductivity of yersinin pores was decreased by one order of magnitude. The most drastic changes in the conductivity of the model membrane were observed at pH 5.8, whereas a further decrease of pH to 5.0 resulted in the closure of porin channels. It was concluded that the observed changes in the pore-forming properties of yersinin in a narrow range of pH represent an early step in the adaptation of bacteria to the changing conditions of the environment and entail control over the biosynthesis of nonspecific porins. The pH-dependent changes in the structure and pore-forming properties of yersinin provide additional evidence in favor of conformational and functional plasticity of porins.     

Nanoelectrochemistry of cytochrome P450s: Direct electron transfer and electrocatalysis

Direct electron transfer has been demonstrated between cytochrome P450 2B4 (CYP2B4), P450 1A2 (CYP1A2), sterol 14α-demethylase (CYP51MT) and screen printed graphite electrodes, modified by gold nanoparticles and didodecyldimethyl ammonium bromide (DDAB). The proposed method for preparation of enzymatic nanostructured electrodes may be used for electrodetection of this hemoprotein provided that 2–200 pmol P450 per electrode has been adsorbed. Electron transfer, direct electrochemical reduction and interaction with P450 substrates (oxygen, benzphetamine, lanosterol) and inhibitor ketoconazole were analyzed using cyclic voltammetry (CV), square wave (SWV) or differential pulse (DPV) voltammetry, and amperometry.