Treatment of viral and neoplastic diseases with double-stranded RNA derivatives and other new agents

Many attempts have been made to inhibit viral and neoplastic diseases by targeting the RNA system. The pathophysiologic significance of the microRNA system and the therapeutic potential of its manipulation are discussed. Studies of double-stranded RNA derivatives are reviewed. The therapeutic potential of one of these compounds, polyI:MPC, is emphasized. Studies of other related antiviral and antineoplastic agents are discussed, including 2'-deoxyoligocytidilates and telomerase inhibitors.     

Species Structure of Plankton Microalgae on the Coast of the Sea of Okhotsk on Sakhalin Island

The results of long-term studies of the species structure of microalgae plankton of the coast of the Sea of Okhotsk of Sakhalin Island were summarized. There were 227 species and 4 intraspecific taxa attributed to 8 divisions. The greatest number of species was represented by the divisions Bacillariophyta (112 species and 3 intraspecific taxa) and Dinophyta (96 and 1 respectively). For the first time 5 diatom, 4 dinoflagellate, and 1 euglenophyte species were recorded for the Sea of Okhotsk.     

A Modified Integrated Genetic Model for Risk Prediction in Younger Patients with Acute Myeloid Leukemia

BackgroundAlthough cytogenetics-based prognostication systems are well described in acute myeloid leukemia (AML), overall survival (OS) remains highly variable within risk groups. An integrated genetic prognostic (IGP) model using cytogenetics plus mutations in nine genes was recently proposed for patients ≤60 years to improve classification. This model has not been validated in clinical practice.ConclusionsThe IGP model was not completely validated in our cohort. However, mutations in six out of the nine genes can be used to characterize survival (NPMI, IDH1, IDH2, FLT3-ITD, TET2, DNMT3A) and allow for more robust prognostication in the patients who are re-categorized by the IGP model. These mutations should be incorporated into clinical testing for younger patients outside of clinical trials, in order to guide therapy.     

Phosphorylation regulates tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase Cgamma1, Grb2, and Src family kinases

The microtubule-associated protein tau can associate with various other proteins in addition to tubulin, including the SH3 domains of Src family tyrosine kinases. Tau is well known to aggregate to form hyperphosphorylated filamentous deposits in several neurodegenerative diseases (tauopathies) including Alzheimer disease. We now report that tau can bind to SH3 domains derived from the p85alpha subunit of phosphatidylinositol 3-kinase, phospholipase Cgamma1, and the N-terminal (but not the C-terminal) SH3 of Grb2 as well as to the kinases Fyn, cSrc, and Fgr. However, the short inserts found in neuron-specific isoforms of Src prevented the binding of tau. The experimentally determined binding of tau peptides is well accounted for when modeled into the peptide binding cleft in the SH3 domain of Fyn. After phosphorylation in vitro or in transfected cells, tau showed reduced binding to SH3 domains; no binding was detected with hyperphosphorylated tau isolated from Alzheimer brain, but SH3 binding was restored by phosphatase treatment. Tau mutants with serines and threonines replaced by glutamate, to mimic phosphorylation, showed reduced SH3 binding. These results strongly suggest that tau has a potential role in cell signaling in addition to its accepted role in cytoskeletal assembly, with regulation by phosphorylation that may be disrupted in the tauopathies including Alzheimer disease.     

The blood glucose content in newborn rats depending on level and pattern of spontaneous motor activity

Earlier we have shown that administration to newborn rats of the pentose phosphate cycle inhibitor hydroquinone leads to a change in intensity and pattern of spontaneous periodic motor activity (SPMA) characteristic of early stages of development. The most typical was the disappearance of the rest period from the near-minute “activity-rest” cycle and the appearance of uninterrupted motor activity. In several cases, especially after 10 days of development, there was noted an enhancement in the SMPA pattern of the motor activity complexes following in the decasecond rhythm. In this study, on the 3–10-day old rats maintained under conditions of free behavior there was studied the blood glucose content in the animals at various periods of the activity-rest cycle. Apart from the SPMA phase, its composition (pattern) characterizing the maturity level and functional state of spinal motor centers was taken into account. In the 3, 7 and 10-day old rats at the rest period, the glucose concentration was established to differ depending on the motor activity pattern. In the case of the decasecond periodicity, it amounts to 5.7 ± 0.2, 6.3 ± 0.3, and 7.5 ± 0.3 mmol/l, while at the minute one—6.1 ± 0.4, 7.8 ± 0.3, and 7.8 ± 0.1 mmol/l. At the moment of bursts of motor excitation, the glucose concentration falls to 5.2 ± 0.1, 6.1 ± 0.4, and 7.1 ± 0.3 mmol/l at the decasecond and to 5.4 ± 0.5, 6.7 ± 0.2, and 7.6 ± 0.3 mmol/l at the near-minute rhythm (for the 3-, 7-, and 10-day old animals, respectively). The results obtained on the 5-day rat pups differ qualitatively from those observed in other age groups. Thus, the glucose concentration at the rest period amounts to 6.8 ± 0.2 at the decasecond and to 6.7 ± 0.4 mmol/l at the nearminute periodicity. At the period of motor excitation accompanied by the presence of the decasecond activity rhythm, the glucose concentration falls to the level of 6.0 ± 0.2 mmol/l by differing statistically significantly from the observed one in the rest state. In the case of the appearance of the minute rhythm, the glucose concentration amounts to 5.8 ± 0.3 mmol/l. The obtained data indicate that reproduction of the minute and decasecond rhythms recorded in composition of SPMA is accompanied by a change in the blood serum glucose level. The degree of a decrease of its concentration correlates with a certain activity rhythm: at the decasecond one the fall is 9, 13, 3, and 7%, whereas at the minute rhythm—11, 13, 14, and 2% (for the 3-, 5-, 7- and 10-day old rats, respectively). It is to be noted that a certain effect on the activity pattern is produced by the degree of satiety of the rat pups, the gastric emptying being accompanied by an increase in expression of the decasecond rhythm and of brief jerks. Besides, there occur the significant seasonal oscillations of the blood serum glucose concentration in the newborn rat pups—at the summer period it is statistically significantly higher than at the winter—spring period.