Arginine-rich cross-linking peptides with different SV40 nuclear localization signal content as vectors for intranuclear DNA delivery

The major barriers for intracellular DNA transportation by cationic polymers are their toxicity, poor endosomal escape and inefficient nuclear uptake. Therefore, we designed novel modular peptide-based carriers modified with SV40 nuclear localization signal (NLS). Core peptide consists of arginine, histidine and cysteine residues for DNA condensation, endosomal escape promotion and interpeptide cross-linking, respectively. We investigated three polyplexes with different NLS content (10?mol%, 50?mol% and 90?mol% of SV40 NLS) as vectors for intranuclear DNA delivery. All carriers tested were able to condense DNA, to protect it from DNAase I and were not toxic to the cells. We observed that cell cycle arrest by hydroxyurea did not affect transfection efficacy of NLS-modified carriers which we confirmed using quantitative confocal microscopy analysis. Overall, peptide carrier modified with 90?mol% of SV40 NLS provided efficient transfection and nuclear uptake in non-dividing cells. Thus, incorporation of NLS into arginine-rich cross-linking peptides is an adequate approach to the development of efficient intranuclear gene delivery vehicles.     

Optimal allocation between nutrient uptake and growth in a microbial trichome

 A microbial trichome grows by assimilating nutrients from its environment, and converting these into catalytic macro-molecular machinery. This machinery may be divided into assimilatory machinery and proliferative machinery. The former type is involved in nutrient uptake, whereas the latter type enables the trichome to grow. The cells in the trichome are faced with an allocation problem: given the availability of nutrients in the environment, how many macro-molecular building blocks should be allocated to the synthesis of assimilatory machinery, and how many to the synthesis of proliferative machinery? We answer this question for a particular model, which is a generalization of the Droop quota model. We formulate a two-dimensional non-linear optimal control problem, corresponding to this model. An optimal allocation regime with a singular segment is derived, based on Pontryagin’s maximum principle. We give a direct proof of optimality. We discuss how actual biological cells might implement this optimal regime. Received: 16 December 1996 / Revised version: 14 September 1997     

Metabolism of liver polyphosphoisositides in rats during stimulating and depressing influences on the organism]

Under normal conditions the rate of the 32P-orthophosphate incorporation into the polyphosphoinositides was 30--40 times greater than into the other phospholipid fraction of the normal rat liver. There was a rapid postmortem alteration of the polyphosphoinositide content in the liver. Under conditions studied the changes in the phospholipid content were revealed in the polyphosphoinositide fractions only. The changes in the content and in the metabolic intensity of rat polyphosphoinositide in the liver were in many respects similar to those in the brain. Polyphosphoinositide fractions were found to be the most labile of all the phospholipid fractions in the rat liver.     

Effects of the Calmodulin Antagonist W7 on Resveratrol Biosynthesis in Vitis amurensis Rupr.

The calmodulin antagonist N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7) binds to calmodulzin and inhibits Ca²⁺/calmodulin-regulated enzyme activities. In plant cells, W7 inhibits the activity of calcium-dependent protein kinases (CDPKs)—the major calcium sensors in plants. In the present study, we examined the effect of W7 on increased resveratrol biosynthesis and expression of CDPK and stilbene synthase (STS) genes in a cell culture of Vitis amurensis Rupr. We used coumaric acid (CA), salicylic acid (SA), and phenylalanine (Phe) to increase the content of resveratrol in V. amurensis calli, since its content is low under standard conditions. W7 significantly decreased resveratrol production and expression of STS genes in CA-, SA-, and Phe-treated grape cells. Also, treatment of the V. amurensis calli with SA, Phe, or CA considerably increased expression of VaCDPK1a (with SA, Phe), VaCDPK1L (with SA, Phe), VaCDPK2a (with Phe) genes, and decreased expression of VaCDPK3a (with CA). Addition of W7 to CA-, SA-, and Phe-treated grape cells reversed this effect, resulting in increased VaCDPK3a expression and decreased VaCDPK1a, VaCDPK1L, and VaCDPK2a expression. The results obtained suggest that CDPK activities might play an important role in resveratrol biosynthesis.     

Age-Dependent Approach to Search for Genetic Variants Associated with Myocardial Infarction

Molecular Biology - Myocardial infarction (MI), one of the most common manifestations of cardiovascular system aging, is often fatal. The vast majority of studies on genetic susceptibility to...     

Variability of the Mitochondrial Genome and Development of the Primary Progressing form of Multiple Sclerosis

Molecular Biology - Recently, it has been shown that dysfunction of mitochondria is an important component of the molecular mechanisms of the development of many neurodegenerative diseases. These...