The action of α-amanitin in vivo on the synthesis and maturation of mouse liver ribonucleic acids

α-Amanitin acts in vitro and in vivo as a selective inhibitor of nucleoplasmic RNA polymerases. Treatment of mice with low doses of α-amanitin causes the following changes in the synthesis, maturation and nucleocytoplasmic transfer of liver RNA species. 1. The synthesis of the nuclear precursor of mRNA is strongly inhibited and all electrophoretic components are randomly affected. The labelling of cytoplasmic mRNA is blocked. These effects may be correlated with the rapid and lasting inhibition of nucleoplasmic RNA polymerase. 2. The synthesis and maturation of the nuclear precursor of rRNA is inhibited within 30min. (a) The initial effect is a strong (about 80%) inhibition of the early steps of 45S precursor rRNA maturation. (b) The synthesis of 45S precursor rRNA is also inhibited and the effect increases from about 30% at 30min to more than 70% at 150min. (c) The labelling of nuclear and cytoplasmic 28S and 18S rRNA is almost completely blocked. The labelling of nuclear 5S rRNA is inhibited by about 50%, but that of cytoplasmic 5S rRNA is blocked. (d) The action of α-amanitin on the synthesis of precursor rRNA cannot be correlated with the slight gradual decrease of nucleolar RNA polymerase activity (only 10–20% inhibition at 150min). (e) The inhibition of precursor rRNA maturation and synthesis precedes the ultrastructural lesions of the nucleolus detected by standard electron microscopy. 3. The synthesis of nuclear 4.6S precursor of tRNA is not affected by α-amanitin. However, the labelling of nuclear and cytoplasmic tRNA is decreased by about 50%, which indicates an inhibition of precursor tRNA maturation. The results of this study suggest that the synthesis and maturation of the precursor of rRNA and the maturation of the precursor of tRNA are under the control of nucleoplasmic gene products. The regulator molecules may be either RNA or proteins with exceedingly fast turnover.     

Developmental changes in high-affinity uptake of GABA by cultured neurons

High-affinity uptake of [³H]-aminobutyric acid (GABA) was studied in cultures of neonatal rat cortical neurons grown on pre-formed monolayers of non-neuronal (glial) cells. Both the maximum rate (V _max) and, to a smaller extent, theK _m of [³H]GABA uptake increased with time. In addition, in parallel with these changes, 2,4-diaminobutyric acid and cis-3-aminocyclohexane-1-carboxylic acid (ACHC), compounds which are considered typical substrate/inhibitors of GABA uptake in neurons, became progressively stronger inhibitors of [³H]GABA uptake. Consequently, the present results may mean that the studies using uptake, of [³H]GABA, [³H]ACHC, or [³H]DABA as a specific marker for GABAergic neurons differentiating during the ontogenetic development of the central nervous system may have to be interpreted with caution.     

Changes in vestibular postural response determined by information content of visual feedback

Electrical unipolar monoaural stimulation of the labyrinth led to body sway mainly on a frontal plane in normal human subjects in a standing position. Early and late stages of response with latencies of 120–200 and 200–500 msec respectively changing in size in accordance with conditions of visual control were distinguished in the stabilographic response. Maximum response was recorded when the eyes were closed. Response declined upon opening the eyes, fixing the gaze on a static target, and with visual feedback according to stabilograms. The early and late components declined by 10–20 and 50–70% respectively in all cases. Fixing the gaze, in darkness, on an illuminated light spot stationary in relation to the head had no effect on level of response. Once the expected direction of body sway had been imparted, a significant and almost identical decrease of 70–80% in both components took place with the gaze fixed, however. Early and late components of vestibulomotor response are thought to be mediated by regulatory mechasisms with differing time courses and functional connections.Institute of Research into Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vo. 22, No. 1, pp. 80–87, January–February, 1990.     

Mapping in the mouse of the region homologous to the rat growth and reproduction complex (grc)

Offprint requests: J. Klein.     

Nephrotoxic effect of the specific brain serotonin depletor para-chlorophenylalanine

Brain serotonin depletion induced by peripheral parachlorophenylalanine (pCPA) is frequently used to evaluate the role of the central serotoninergic system in the regulation of a number of physiological functions, including the secretion of renin by the kidney. We found that due to the treatments applied in the protocol used for the investigation of pCPA effect on renin and vasopressin secretion in rats (300 mg/kg i.p. 64 and 40 h before sacrifice) renal injury was induced as well. Typical changes indicating acute renal failure were observed--an initial polyuria, natriuresis and body mass loss, succeeded by oliguria, decreased glomerular filtration rate, and salt and creatinine retention. Morphological changes in the glomeruli included a thickening of the basal membranes, a confluence and a reduced number of podocyte pedicles. A slight to moderate granular degeneration was observed in epithelial cells of the proximal convoluted tubule, combined with mitochondrial changes--an increase in number, matrix disorganization, and myelin degeneration. In conclusion, the renal function changes after i.p. pCPA may be due not to brain serotonin depletion-alone, but also to nephrotoxic effect.     

Respiratory Rate as a Regulatory Factor in the Biosynthesis of the Denitrification Pathway of the Bacterium Paracoccus denitrificans

The decrease in the electron flow of the aerobic respiratory chain of the bacterium Paracoccus denitrificans, owing to either the drop in the saturation of terminal oxidases by oxygen or to the inhibition of the rate of respiration by azide or nitrite, resulted in the synthesis of dissimilatory nitrate reductase and nitrite reductase. The dependence of the resulting activities of the two enzymes (after a three-hour adaptation) on the initial value of the parameter V_max/k_La (oxidase activity of the volume unit of the culture divided by the volumetric oxygen transfer coefficient) or on the concentrations of the inhibitors had a similar form, characterized by the appearance of a maximum. The increasing parts of the obtained curves reflect the synthesis of enzymes, probably initiated by the increase in the intracellular degree of reduction, the subsequent drop being evidently in connection with the lack of metabolic energy for biosynthesis. The possible mechanisms of the effect of nitrogenous terminal acceptors (NO^-₃ and NO^-₂) on the formation of the denitrification pathway are discussed.     

Cloning and characterization of a 70 kd heat shock cognate (hsc70) gene from the zebrafish (Danio rerio)

The heat shock 70 family of proteins is one of the most highly conserved among all species. The genes encoding these proteins have been cloned and sequenced from bacterial species to humans with a high degree of homology preserved throughout evolution. Here we describe the cloning and characterization of a cDNA encoding a 70 kd heat shock cognate (hsc70) gene from the zebrafish (Danio rerio). A high degree of conservation is observed among hsc70 genes of other species as shown by phylogenetic analysis. The characterization of a hsc70 gene in the zebrafish provides a marker for studying the role of a constitutively expressed member of the hsp70 family in an important developmental and evolutionary model system.     

Mathematical model for the ecosystem response of Lake Ladoga to phosphorus loading

The ecosystem response model described in this paper combines an ecosystem model and a three-dimensional circulation model of Lake Ladoga developed earlier by the authors. The ecosystem model describes the process of Lake Ladoga eutrophication, and its biological submodel describes changes in the phyto- and zooplankton. In the earlier model version, lake circulation was determined using a two-dimensional hydrodynamical model which was not completely adequate. The present model allows calculation of the distributions of phyto- and zooplankton and mineral phosphorus and nitrogen. One of its main advantages is that reliable computations of the ecosystem dynamics over an extended period of time are possible. The response of the ecosystem to different levels of phosphorus pollution loading and to weather conditions is studied.     

Frequency tuning curves of the dolphin's hearing: envelope-following response study

Simultaneous tone-tone masking in conjunction with the envelope-following response (EFR) recording was used to obtain tuning curves in dolphins (Turslops truncatus). The EFR was evoked by amplitude-modulated probes of various frequencies. A modulation rate of 600 Hz was found to fit the requirement to have a narrow spectrum and evoke EFR of large amplitude. Tuning curves were obtained within the frequency range from 11.2 to 110 kHz. The Q₁₀ values of the obtained tuning curves varied from 12–14 at the 11.2 kHz center frequency to 17–20 at the 64–90 kHz frequencies.Abbreviations ABR auditory brainstem response - EFR envelope following response - ERB equivalent rectangular bandwidth