A new role for PGRP-S (Tag7) in immune defense: lymphocyte migration is induced by a chemoattractant complex of Tag7 with Mts1

PGRP-S (Tag7) is an innate immunity protein involved in the antimicrobial defense systems, both in insects and in mammals. We have previously shown that Tag7 specifically interacts with several proteins, including Hsp70 and the calcium binding protein S100A4 (Mts1), providing a number of novel cellular functions. Here we show that Tag7–Mts1 complex causes chemotactic migration of lymphocytes, with NK cells being a preferred target. Cells of either innate immunity (neutrophils and monocytes) or acquired immunity (CD4⁺ and CD8⁺ lymphocytes) can produce this complex, which confirms the close connection between components of the 2 branches of immune response.     

Prostaglandins, steroids and reception (an attempt to model the structure of the active centers of adrenoreception)

On the basis of numerous results of investigations on adrenergic systems, an orientational model of the adrenoreceptor (AR) is postulated. Its active center includes low-molecular-weight components--prostaglandins (PGE, PGF), steroids (cortisone, hydrocortisone), S+-adenosylmethionine, Ca, Mg, and Mn ions. Appraisal of the stereospecific characteristics of such a functional unit of AR explains the difference in the nature and magnitude of the effects of interaction of the catecholamines, their agonists and antagonists will the so-called alpha- and beta-AR. Depending on the organ or tissue in which the AR is located, its protein subunits comprise adenylcyclase (beta-AR) or Na,K-ATPase (alpha-AR). An obligatory component of the AR is catechol-O-methyltransferase. The model elaborated describes satisfactorily the molecular mechanisms of action of many pharmacological agents, explains why attempts to isolate and reconstruct the AR have proved fruitless, and gives grounds for rejecting the hypothesis that there exist steroid, prostaglandin, and purinergic receptors, linking the exceptionally high and diverse activity of these biologically active substances with their participation in adrenoreception among other reasons. A conception of the active centers of the AR as low-molecular-weight entities permits the explanation of such phenomena as the desensitization of the AR, the "interconversion" of beta-AR into alpha-AR with a change in the parameters of the medium, and certain components of the pathogenesis of bronchial asthma, etc.     

Interaction of Lipophilic Conjugates of Modified siRNAs with Hematopoietic Cells In Vitro and In Vivo

Russian Journal of Bioorganic Chemistry - Delivery of siRNAs to blood cells is one of the most difficult tasks since there are no efficient and nontoxic methods of delivering nucleic acids to these...     

Imaging of surface cell antigens on the tumor sections of lymph nodes using fluorescence quantum dots

The usefulness of quantum dots for the immunofluorescent detection of surface antigens on the lymphoid cells has been studied. To optimize quantum dots detection we have upgraded fluorescent microscope that allows obtaining multiple images from different quantum dots from one section. Specimens stained with quantum dots remained stable over two weeks and practically did not bleach under mercury lamp illumination during tens of minutes. Direct conjugates of primary mouse monoclonal antibodies with quantum dots demonstrated high specificity and sufficient sensitivity in the case of double staining on the frozen sections. Because of the high stability of quantum dots' fluorescence, this method allows to analyze antigen coexpression on the lymphoid tissue sections for diagnostic purposes. The spillover of fluorescent signals from quantum dots into adjacent fluorescent channels, with maxima differing by 40 nm, did not exceed 8%, which makes the spectral compensation is practically unnecessary.     

A sea anemone polypeptide toxin inhibiting the ASIC3 acid-sensitive channel

A polypeptide toxin ??-AnmTX Hcr 1b-1 with a molecular mass of 4537 Da was isolated from the whole extract of the sea anemone Heteractis crispa by multistage liquid chromatography. According to a homology search using the BLAST algorithm, the novel toxin was referred to the group of the known sea anemone toxins BDS and APETx with the homology of the amino acid sequence not exceeding 50%. In electrophysiological studies on the receptors expressed in Xenopus laevis oocytes the toxin inhibited the amplitude of the fast component of the integral ASIC3 current. The calculated IC₅₀ value was 5.5 ± 1.0 ??M. Among the known polypeptide blockers of ASIC3 channels the ??-AnmTX Hcr 1b-1 toxin was the least potent inhibitor, which can be explained, in our opinion, by a small amount of charged amino acid residues in its structure.     

Lateral modulation of the hypoglycemic action of insulin

The results of the experimental investigation on 15 rabbits are presented here. Hypoglycemic action of the standard exogenic insulin dose strengthened after performing transcerebral lateral electrostimulation on the right side with the weak current impulse.     

Peptide Modulators of ASIC Channels of the Sea Anemone Urticina aff. coriacea (Cuvier, 1798) from the Sea of Okhotsk

Russian Journal of Marine Biology - A search for biologically active peptides has been performed in an aqueous extract of the sea anemone Urticina aff. coriacea (Cuvier, 1798) (Actiniidae) from the...     

Conformational stability of serine proteinase inhibitor from the sea anemone Heteractis crispa

The influence of different environmental values of the pH and temperature on the spatial organization of serine proteinase inhibitor from the sea anemone Heteractis crispa (=Radianthus macrodactylus) on the level of tertiary and secondary structure was studied by CD spectroscopy. The molecule InhVJ was shown to possess a high conformational thermo- and pH-stability. We determined the point of conformational thermotransition of polypeptide (70 degrees C) after which the molecule gets denaturational stable state with conservation of 80% proteinase inhibitory activity. The significant partial reversible changes of molecule spatial organization were established to occur at the level of tertiary structure in the process of acid-base titration in the range of pH 11.0-13.0. This can be explained by of ionization of tyrosine residues. The molecule InhVJ is conformationally stable at the low pH values (2.0). The quenching of tyrosine residues by acrylamide showed that two of these residues are accessible to the quencher in full, while the third part is available.     

Investigation of the complex antibiotic INA-5812

A concentrate with the antimicrobial activity has been isolated from the culture broth of Streptomyces roseoflavus INA-Ac-5812. Its further fractionation by reversed-phase HPLC has resulted in six fractions. It has been established by MALDI-TOF and ESI-MSⁿ precision mass-spectrometry methods that the main components of the complex antibiotic are several closely related compounds, presumably of a glycopeptide nature. The fraction containing an individual component with a mass of 1845.788 Da has been characterized by UV/Vis absorbance and fluorescence spectra, amino acid analysis, and derivatization with tris(2,6-dimethoxyphenyl)methyl cation. The activity of fractions against pathogenic microbes has been studied. The results allow the supposition that the INA-5812 antibiotic complex is a glyco- or lipoglycopeptide antibiotic of a new type, which is very promising for further study.