Partial trisomy 11q as the result of sporadic translocation

Summary Partial trisomy 11q due to a sporadic translocation was found in a mentally retarded girl with multiple abnormalities. The proportion of sporadic translocations involved in the total incidence of partial trisomies is discussed.     

Recombinations during DNA cloning

RecA-independent recombinations accompanying the processes of plasmids preparation and cloning into Escherichia coli cells are induced within the short direct and inverted repeats of several types.     

Enhanced neuronal K+ conductance: a possible common mechanism for sedative-hypnotic drug action

It is commonly thought that central nervous system depressant drugs exert their actions through enhancement of gamma-aminobutyrate (GABA)-mediated mechanisms. Recently, the cellular electrophysiological evidence from this laboratory and others suggests that both sedative hypnotics and general anaesthetics inhibit central neurons by increasing potassium conductance (GK). We have utilized the mammalian in vitro hippocampal and cerebellar slice preparations at 34-36 degrees C. Intracellular recordings from CA1, CA3, and cerebellar Purkinje cells were obtained. Low dose (sedative) concentrations of ethanol (less than or equal to 20 mM), two different benzodiazepines (midazolam and clonazepam in low nanomolar concentrations), and pentobarbital (10(-6) to 10(-4) M) were applied by pressure ejection or were bath perfused. All drugs caused a hyperpolarization with decreased spontaneous activity, and enhanced post spike afterhyperpolarizations (AHPs). These long-lasting AHPs are presumably due to enhanced calcium-mediated GK. Increased responsiveness to focally applied GABA was only seen at higher doses (ethanol, 100 mM; midazolam, 10(-7) M; pentobarbital, 10(-4) M). These data suggest that the above neurodepressant drugs, when applied at sedative doses to hippocampal pyramidal cells, enhance GK and not the actions of GABA.     

Cell-free expression of visual arrestin. Truncation mutagenesis identifies multiple domains involved in rhodopsin interaction.

Visual arrestin plays an important role in regulating light responsiveness via its ability to specifically bind to the phosphorylated and light-activated form of rhodopsin. To further characterize rhodopsin/arrestin interactions we have utilized a rabbit reticulocyte lysate translation system to synthesize bovine visual arrestin. The translated arrestin (404 amino acids) was demonstrated to be fully functional in terms of its ability to specifically recognize and bind to phosphorylated light-activated rhodopsin (P-Rh*). Competitive binding studies revealed that the in vitro synthesized arrestin and purified bovine visual arrestin had comparable affinities for P-Rh*. In an effort to assess the functional role of different regions of the arrestin molecule, two truncated arrestin mutants were produced by cutting within the open reading frame of the bovine arrestin cDNA with selective restriction enzymes. In vitro translation of the transcribed truncated mRNAs resulted in the production of arrestins truncated from the carboxyl terminus. The ability of each of the mutant arrestins to bind to dark (Rh), light-activated (Rh*), dark phosphorylated (P-Rh), and light-activated phosphorylated rhodopsin were then compared. Arrestin lacking 39 carboxyl-terminal residues binds specifically not only to P-Rh* but also to Rh* and P-Rh. This suggests that the carboxyl-terminal domain of arrestin plays an important regulatory role in ensuring strict arrestin binding selectivity to P-Rh*. Arrestin that has only the first 191 amino-terminal residues predominately discriminates the phosphorylation state of the rhodopsin; however, it also retains some binding specificity for the activation state. These results suggest that the amino-terminal half of arrestin contains key rhodopsin recognition sites responsible for interaction with both the phosphorylated and light-activated forms of rhodopsin.     

Manipulation of Very Few Receptor Discriminator Residues Greatly Enhances Receptor Specificity of Non-visual Arrestins

Based on the identification of residues that determine receptor selectivity of arrestins and the analysis of the evolution in the arrestin family, we introduced 10 mutations of "receptor discriminator" residues in arrestin-3. The recruitment of these mutants to M2 muscarinic (M2R), D1 (D1R) and D2 (D2R) dopamine, and β(2)-adrenergic receptors (β(2)AR) was assessed using bioluminescence resonance energy transfer-based assays in cells. Seven of 10 mutations differentially affected arrestin-3 binding to individual receptors. D260K and Q262P reduced the binding to β(2)AR, much more than to other receptors. The combination D260K/Q262P virtually eliminated β(2)AR binding while preserving the interactions with M2R, D1R, and D2R. Conversely, Y239T enhanced arrestin-3 binding to β(2)AR and reduced the binding to M2R, D1R, and D2R, whereas Q256Y selectively reduced recruitment to D2R. The Y239T/Q256Y combination virtually eliminated the binding to D2R and reduced the binding to β(2)AR and M2R, yielding a mutant with high selectivity for D1R. Eleven of 12 mutations significantly changed the binding to light-activated phosphorhodopsin. Thus, manipulation of key residues on the receptor-binding surface modifies receptor preference, enabling the construction of non-visual arrestins specific for particular receptor subtypes. These findings pave the way to the construction of signaling-biased arrestins targeting the receptor of choice for research or therapeutic purposes.     

Distribution of microorganisms in the oil-polluted ground of vadose and saturation zones

The ground polluted with oil products was analyzed at a depth of 0.5–7.8 m (loamy soil), 11.5–13.0 m (gravelstone), 13.0–15.0 m (siltstone). It was shown that the distribution of oil products and microorganisms in the ground over the profile depends on the hydrogeological properties of the rock (porosity, hydraulic conductivity). The number of aerobic heterotrophic microorganisms varied from 10⁶–10⁷ CFU/g, the fraction of hydrocarbon-oxidizing ones increased with depth from 30 to 85%. The number of anaerobic microorganisms was comparable to the number of aerobic ones. The number of psychrotrophs and psychrophiles increases with depth; in the lower horizon these organisms prevail over the number of mesophiles.     

Effect of hemosorption on the elimination of an amphotericin B derivative in experimental studies

Possible extracorporeal removal of a novel water soluble derivative of amphotericin B (NWSDA) from the host was studied. The bench tests demonstrated that actilen, a fibrous carbon adsorbent, was the optimal carbon sorbent for sorption of NWSDA. It was shown in the acute experiments on animals that during the hemosorption the antibiotic blood concentration on the outlet of the column was significantly lower than that on the inlet. Still, the NWSDA concentration in the blood lowered slowly which was likely due to the return of the antibiotic to the blood from the tissues.     

Cellular mechanisms of the development of primary arterial hypertension

Modern views on the contraction and dilatation mechanisms of vessel smooth muscle cells are discussed. The data on main role of the cation-transport cell system function peculiarities in the primary arterial hypertension genesis, a relation cell hyperreactivity to those peculiarities and its genetical origin, are reported. It is supposed that the hereditary predisposition forms certain functional lability of cellular elements in different organism tissues, and, in consequence of that, the environmental influences can provoke the development of primary arterial hypertension.