Genetic regulation of the processes of neurogenesis

Neurons proved to be a convenient experimental model for studies of regulatory properties of the genetic apparatus during development. Formation of neuronal ensembles is controlled by multiple modifier-genes at different levels. The following gene groups can be distinguished: 1) Genes that function in differentiating neurons; 2) Genes that function in other neurons; 3) Genes that function in glial cells; 4) Genes that function in surrounding tissues; 5) Genes that function at the organism level.     

Exonuclease V from Saccharomyces cerevisiae. A 5'----3'-deoxyribonuclease that produces dinucleotides in a sequential fashion

A novel deoxyribonuclease, exonuclease V, has been purified approximately 30,000-fold from Saccharomyces cerevisiae. Exonuclease V is localized in the nucleus. The nuclease degrades single-stranded, but not double-stranded, DNA from the 5'-end. The products of exonuclease action are dinucleotides, except the 3'-terminal tri- and tetranucleotides which are not degraded. Studies with synthetic oligo- and polynucleotides with specified sequence elements showed that exonuclease V cleaves off dinucleotides as primary digestion products. Thus, the polymers (pT)9pA(pT)n and (pT)10pA(pT)n yielded pTpA and pApT as digestion products, respectively. Removal of the 5'-terminal phosphate from the DNA substrate results in reduced binding of the enzyme to the substrate. In addition, the initial hydrolytic cut by exonuclease V on the dephosphorylated substrate produces a mixture of dinucleoside monophosphates and trinucleoside diphosphates. The enzyme is processive in action.     

Muscarinic acetylcholine receptor activation causes inhibition of cyclic AMP accumulation, prolactin and growth hormone secretion in GH3 rat anterior pituitary tumour cells

Acetylcholine, oxotremorine and carbachol, compounds that exhibit muscarinic agonist activity, maximally inhibited basal prolactin secretion from GH3 cells by approx. 50% and intracellular cyclic AMP levels by approx. 20%. Both parameters were inhibited with similar potencies by each agonist. These inhibitory effects were blocked by a muscarinic but not by a nicotinic receptor antagonist. In the presence of VIP or IBMX, which raise intracellular cyclic AMP levels and stimulate hormone release, the degree of muscarinic inhibition was increased, but the potency remained unchanged. Similar changes in the secretory rate of prolactin and growth hormone occurred in these and in cell perifusion experiments. These results suggest that the inhibition of hormone secretion from GH3 cells by muscarinic agonists is mediated by a decrease in intracellular cyclic AMP levels.     

Information services in medical mycology

The need for information services in medical mycology is discussed. The information service provided by the Review of Medical and Veterinary Mycology is described and compared with other information services.     

Kinetics of D-glucose and 2-deoxy-D-glucose transport by Rhodotorula glutinis

The yeast Rhodotorula glutinis (Rhodosporidium toruloides) is capable of accumulative transport of a wide variety of monosaccharides. Initial velocity studies of the uptake of 2-deoxy-D-glucose were consistent with the presence of at least two carriers for this sugar in the Rhodotorula plasma membrane. Non-linear regression analysis of the data returned maximum velocities of 0.8 +/- 0.2 and 2.0 +/- 0.2 nmol/min per mg (wet weight) and Km values of 18 +/- 4 and 120 +/- 20 microM, respectively, for the two carriers. Kinetic studies of D-glucose transport also revealed two carriers with maximum velocities of 1.1 +/- 0.4 and 2.4 +/- 0.4 nmol/min per mg (wet weight) and Km values of 12 +/- 3 and 55 +/- 12 microM. As expected, 2-deoxy-D-glucose was a competitive inhibitor of D-glucose transport. Ki values for the inhibition were 16 +/- 8 and 110 +/- 40 microM. These Ki values were in good agreement with the Km values for 2-deoxy-D-glucose transport. D-Xylose, the 5-deoxymethyl analog of D-glucose, appears to utilize the D-glucose/2-deoxy-D-glucose carriers. This pentose was observed to be a competitive inhibitor of D-glucose (Ki values = 0.14 +/- 0.06 and 5.6 +/- 1.6 mM) and 2-deoxy-D-glucose (Ki values = 0.15 +/- 0.07 and 4.6 +/- 1.2 mM) transport.     

WSV 2019: The First Committee Meeting of the World Society for Virology

The World Society for Virology (WSV) was founded and incorporated as a nonprofit organization in the United States in 2017. WSV seeks to strengthen and support both virological research and virologists who conduct research of viruses that affect humans, other animals, plants, and other organisms. One of the objectives of WSV is to connect virologists worldwide and support collaboration. Fulfilling this objective, virologists from fourteen countries in North America, Europe, Africa, Asia, and the Middle East met on 25–27th August 2019 in Stockholm, Sweden at the Karolinska University Hospital for the first Committee Meeting of WSV. This meeting included compelling keynote and honorary speeches and a series of 18 scientific talks were given encompassing a diverse array of subjects within virology. Followed by the scientific session, a business session was held where multiple aspects and next steps of the society were discussed and charted out.     

Action of Iron Nitrosyl Complexes,NO Donors,on the Activity of Sarcoplasmic Reticulum Ca<Superscript>2+</Superscript>-ATPase and Cyclic Guanosine Monophosphate Phosphodiesterase

The effect of iron nitrosyl complexes, NO donors, of a general formula [Fe₂(L)₂(NO)₄] with functional sulfur-containing ligands (L-3-nitro-phenol-2-yl, 4-nitro-phenol-2-yl, or 1-methyl-tetrazol-5-yl) on the activity of sarcoplasmic reticulum Ca²⁺-ATPase and cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) was studied. The test complexes uncoupled the hydrolytic and transport functions of Ca²⁺- ATPase, thus disturbing the balance of Ca²⁺ ions in cells, which may affect the formation of thrombi and adhesion of metastatic cells to the endothelium of capillaries. They also inhibited the activity of cGMP PDE, thereby contributing to the accumulation of the second messenger cGMP. The studied iron nitrosyl complexes can be considered as potential drugs.     

Virotherapy of the Malignant U87 Human Glioblastoma in the Orthotopic Xenotransplantation Mouse SCID Model

The possibility of glioblastoma virotherapy at intravenous injection of the LIVP–GFP recombinant virus was studied in experimental model of orthotopic xenotransplantation of human glioblastoma cell line U87 to SCID laboratory mice. The LIVP–GFP recombinant virus deficient for thymidine kinase exhibited a significantly greater oncolytic capacity than the original LIVP virus, and an intravenous injection of LIVP–GFP at the early stages of tumorigenesis in mouse brain in most cases resulted in the lysis of the tumor.     

Stereological ultrastructural study of myocardial atrophy in hypokinesia

The myocardium of Wistar rats immobilized for 5, 15 and 30 days was examined by morphometry and stereological methods for evaluating the volumetric and surface density of myofibrils, mitochondria, T system, sarcoplasmic reticulum and for the measurement of the volumetric ratio of different ultrastructures to the density of myofibrils and the surface-volumetric ratio of the main organelles of the cardiomyocyte. Myocardial atrophy was shown to develop in the course of hypokinesia. The 30-day hypokinesia entailed changes in ultrastructural organization of cardiomyocytes, attesting to the tension of intracellular systems responsible for energy supply, of ionic membrane transport and the contractile apparatus.