Assessment of the Reproduction Efficiency of the Atlantic salmon Salmo salar (Salmonidae) in the Kola River (Kola Peninsula) Based on Data on the Density of Juveniles

Journal of Ichthyology - In the Kola River (Kola Peninsula), on the basis of cluster analysis of long-term density data in the nursery areas of underyearlings, wild and wild + hatchery parr of...     

Allosteric modulation balances thermodynamic stability and restores function of ΔF508 CFTR

Most cystic fibrosis is caused by a deletion of a single residue (F508) in CFTR (cystic fibrosis transmembrane conductance regulator) that disrupts the folding and biosynthetic maturation of the ion channel protein. Progress towards understanding the underlying mechanisms and overcoming the defect remains incomplete. Here, we show that the thermal instability of human ΔF508 CFTR channel activity evident in both cell-attached membrane patches and planar phospholipid bilayers is not observed in corresponding mutant CFTRs of several non-mammalian species. These more stable orthologs are distinguished from their mammalian counterparts by the substitution of proline residues at several key dynamic locations in first N-terminal nucleotide-binding domain (NBD1), including the structurally diverse region, the γ-phosphate switch loop, and the regulatory insertion. Molecular dynamics analyses revealed that addition of the prolines could reduce flexibility at these locations and increase the temperatures of unfolding transitions of ΔF508 NBD1 to that of the wild type. Introduction of these prolines experimentally into full-length human ΔF508 CFTR together with the already recognized I539T suppressor mutation, also in the structurally diverse region, restored channel function and thermodynamic stability as well as its trafficking to and lifetime at the cell surface. Thus, while cellular manipulations that circumvent its culling by quality control systems leave ΔF508 CFTR dysfunctional at physiological temperature, restoration of the delicate balance between the dynamic protein's inherent stability and channel activity returns a near-normal state.     

The mechanism of the effect of apterous56f mutation on the reproductive function of Drosophila melanogaster

The effects of L-dihydroxyphenylalanine (L-DOPA) and 20-hydroxyecdysone (20E) were studied with respect to the content of dopamine (DA), intensity of the juvenile hormone (JH) degradation, and fecundity of the wildtype flies (Canton S) and JH-deficient apterous56f mutants (in young females, carrying this mutation, the levels of DA and 20E production were strongly increased). Fly feeding with L-DOPA proved to increase the level of DA in a dose-dependent manner and reduce JH degradation in 2-day-old females of both strains. Feeding with 20E produced the same effect. Treating the wild-type flies with 2.5 mg L-DOPA caused a 24-h delay in beginning of oviposition and reduction in fecundity throughout the experiment. An L-DOPA dose of 1 mg caused no such changes. An experimental increase in 20E titer led to reduced fecundity of the wild-type flies, though no delay in oviposition was observed. In mutant flies, an increase in DA and 20E levels accelerated beginning of oviposition and increased fecundity of young females, though the latter parameter was reduced in mature individuals. Thus, an increase in endogenous DA and 20E characteristic of young apterous56f females is assumed to be a compensatory response that leads to a higher JH titer and induction of vitellogenesis.     

Effect of cyclophosphamide and 61.22 GHz millimeter waves on T-cell, B-cell, and macrophage functions

The present study was undertaken to investigate whether millimeter waves (MMWs) at 61.22 GHz can modulate the effect of cyclophosphamide (CPA), an anti-cancer drug, on the immune functions of mice. During the exposure each mouse's nose was placed in front of the center of the antenna aperture (1.5 x 1.5 cm) of MMW generator. The device produced 61.22 +/- 0.2 GHz wave radiation. Spatial peak Specific Absorption Rate (SAR) at the skin surface and spatial peak incident power density were measured as 885 +/- 100 W/kg and 31 +/- 5 mW/cm(2), respectively. Duration of the exposure was 30 min each day for 3 consecutive days. The maximum temperature elevation at the tip of the nose, measured at the end of 30 min, was 1 degrees C. CPA injection (100 mg/kg) was given intraperitoneally on the second day of exposure to MMWs. The animals were sacrificed 2, 5, and 7 days after CPA administration. MMW exposure caused upregulation in tumor necrosis factor-alpha (TNF-alpha) production in peritoneal macrophages suppressed by CPA administration. MMWs also caused a significant increase in interferon-gamma (IFN-gamma) production by splenocytes and enhanced proliferative activity of T-cells. Conversely, no changes were observed in interleukin-10 (IL-10) level and B-cell proliferation. These results suggest that MMWs accelerate the recovery process selectively through a T-cell-mediated immune response.     

Early influence of the steppe tribes in the peopling of Siberia

The Yakuts, Middle Age Turkic speakers (15th-16th centuries), are widely accepted as the first settlers of the Altai-Baikal area in eastern Siberia. They are supposed to have introduced horses and developed metallurgy in this geographic area during the 15th or 16th century A.D. The analysis of the Siberian grave of Pokrovsk, recently discovered near the Lena River (61 degrees 29' N) and dated by accelerator mass spectrometry from 2,400 to 2,200 years B.P., may provide new elements to test this hypothesis. The exceptional combination of various artifacts and the mitochondrial DNA data extracted from the bone remains of the Pokrovsk man might prove the existence of previous contacts between autochthonous hunters of Oriental Siberia and the nomadic horse breeders from the Altai-Baikal area (Mongolia and Buryatia). Indeed, the stone arrowhead and the harpoons relate this Pokrovsk man to the traditional hunters of the Taiga. Some artifacts made of horse bone and the pieces of armor, however, are related to the tribes of Mongolia and Buryatia of the Xiongnu period (3rd century B.C.). This affinity has been confirmed by the match of the mitochondrial haplotype of this subject with a woman of the Egyin Gol necropolis (Mongolia, 2nd/3rd century A.D.) as well as with two modern Buryats. This result allows us to postulate that contacts between southern steppe populations and Siberian tribes occurred before the 15th century.     

UV-DDB-dependent regulation of nucleotide excision repair kinetics in living cells

Although the basic principle of nucleotide excision repair (NER), which can eliminate various DNA lesions, have been dissected at the genetic, biochemical and cellular levels, the important in vivo regulation of the critical damage recognition step is poorly understood. Here we analyze the in vivo dynamics of the essential NER damage recognition factor XPC fused to the green fluorescence protein (GFP). Fluorescence recovery after photobleaching analysis revealed that the UV-induced transient immobilization of XPC, reflecting its actual engagement in NER, is regulated in a biphasic manner depending on the number of (6-4) photoproducts and titrated by the number of functional UV-DDB molecules. A similar biphasic UV-induced immobilization of TFIIH was observed using XPB-GFP. Surprisingly, subsequent integration of XPA into the NER complex appears to follow only the low UV dose immobilization of XPC. Our results indicate that when only a small number of (6-4) photoproducts are generated, the UV-DDB-dependent damage recognition pathway predominates over direct recognition by XPC, and they also suggest the presence of rate-limiting regulatory steps in NER prior to the assembly of XPA.