Action of dextran-modified hyaluronidase in experimental silicosis

Dextran-modified hyaluronidase was inhaled or intraperitoneally injected for 4 months to mice with silicosis. Stabilized hyaluronidase was shown to have a marked inhibitory effect on the development of lung fibrosis. Drug inhalation proved to be the most effective. An antifibrotic effect of dextran itself has been observed.     

Complex of the herpes simplex virus initiator protein UL9 with DNA as a platform for the design of a new type of antiviral drugs

The protein binding to the origin of replication of the herpes simplex virus type 1 is DNA helicase encoded by the UL9 gene of the herpes virus. The protein specifically binds to two binding sites in the viral DNA replication origins OriS or OriL. In order to determine the role of the UL9 protein in the initiation of replication and find efficient inhibitors of the UL9 activity, we have synthesized a recombinant UL9 protein expressed in E. coli cells. It was found that the recombinant UL9 protein binds to Boxes I and II in OriS and possesses DNA helicase and ATPase activities. In the complex with a fluorescent analog of ATP, two molecules of the ATP analog bind to one protein dimer molecule. It was also found that the UL9 protein in the dimer form can bind simultaneously to two DNA fragments, each containing specific binding sites for the protein. The interaction of the recombinant UL9 protein with the 63-mer double- and single-stranded oligonucleotides OriS and OriS*, which correspond to the origin of replication of herpes simplex virus, has been investigated. From the titrations of OriS and OriS* with ethidium bromide in the presence and absence of the UL9 protein, the equilibrium affinity constants of the protein binding to OriS and OriS* have been determined. A DNase I footprinting study showed that bis-netropsins exhibit preference for binding to the AT cluster in the origin of replication OriS and inhibit the fluctuation opening of AT base pairs in the AT cluster. The drugs also prevent formation of an intermediate conformation of OriS* that involves a disordered tail at the 3′ end and stable Box I-Box III hairpin to which the UL9 helicase selectively binds. The stabilization by bis-netropsins of the AT-rich hairpin at its 3′ end can inhibit the helicase activity. It was concluded that the antiviral activity of bis-netropsins may be associated with the inhibitory effects of bis-netropsins on these two stages of the reaction catalyzed by helicase UL9.     

Changes in morphology of actin filaments and expression of alkaline phosphatase at 3D cultivation of MG-63 osteoblast-like cells on mineralized fibroin scaffolds

3D cultivation of MG-63 osteoblast-like cells on mineralized fibroin scaffolds leads to an increase in the expression of alkaline phosphatase, an early marker of bone formation. Increased expression is associated with the actin cytoskeleton reorganization under the influence of 3D cultivation and osteogenic calcium phosphate component of the microcarrier.     

Characteristics of the complex formation of L-DOPA with chromatin elements from brain cells

It was found that L-DOPA interacts with brain cell chromatin. The life-time of the chromatin-L-DOPA complex is the greatest at 24 degrees C, while at 37 degrees C the destruction of the complex is observed. The specific binding is about 40% at pH 7.4-7.6. The Kd value calculated by the method of Scatchard is equal to 35.10(-9) M. Treatment of the chromatin-L-DOPA complex with DNAase I decreases the chromatin radioactivity by 15-20%. At the same time pronase treatment decreases the chromatin radioactivity by 80%. NaCl (0.2 and 0.4 M) causes the extraction of more than 70% of 3H-DOPA in the complex with chromatin proteins. Thus, L-DOPA interacts predominantly with chromatin proteins.     

The genesis of movement-related human brain potentials in different forms of motor pathology]

To study the role of subcortical structures and cerebellum nuclei in the genesis of the human brain potentials connected with motion patients were examined with parkinsonism and hyperkinetic form of children cerebral paralysis. In one group of patients the motor responses were recorded by means of long-term electrodes implanted with the medical purpose into the ventro-oral group of thalamus nuclei, subcortical nuclei and dentate cerebellum nuclei. In patients of the second group potentials, connected with motion were led from the scalp before and after one-moment destruction in the zone of the same structures. In ventro-oral and reticular thalamus nuclei lateral and medial segments of the pale globe and in the cerebellum dentate nucleus post-motor components were recorded which were considered as electrographic expression of motion realization and completion processes (P2 and N3) and also as slow negative oscillation (component N1), that pointed to participation of the studied structures not only in regulation of voluntary movement but also in the process of movement preparation. Absence of N2 component at recording motor responses from deep electrodes and its sufficient stability at scalp leads gave the reason to suggest that its genesis was connected with the cortex activity.     

Crystal Structure of the pH-Dependent Green Fluorescent Protein WasCFP with a Tryptophan-Based Chromophore at an Extremely Low pH of 2.0

Russian Journal of Bioorganic Chemistry - The green fluorescent protein WasCFP with a tryptophan-based chromophore (Thr65-Trp66- Gly67) exhibits considerable pH-dependent changes of spectral...