BACKGROUND: Diverse antidepressants were recently described to bind to TrkB and drive a positive allosteric modulation of endogenous BDNF. Although neurotrophins such as BDNF can bind to the p75 ...neurotrophin receptor (p75NTR), their precursors are the high affinity p75NTR ligands. While part of an unrelated receptor family capable of inducing completely opposite physiological changes, TrkB and p75NTR feature a cross-like conformation dimer and carry a cholesterol-recognition and alignment consensus in the transmembrane domain. Since such qualities were found crucial for antidepressants to bind to TrkB and drive behavioral and neuroplasticity effects, we hypothesized that their effects might also depend on p75NTR. METHODS: ELISA-based binding assay and NMR spectroscopy were accomplished to assess whether antidepressants would bind to p75NTR. HEK293T cells and a variety of in vitro assays were used to address whether fluoxetine (FLX) or ketamine (KET) would trigger any α- and γ-secretase-dependent p75NTR proteolysis, and lead to p75NTR nuclear localization. Ocular dominance shift was performed with male and female p75KO mice to study the effects of KET and FLX on brain plasticity, in addition to pharmacological interventions to verifying how p75NTR signaling is important for the effects of KET and FLX in enhancing extinction memory in male WT mice and rats. RESULTS: Antidepressants were found binding to p75NTR, FLX and KET triggered the p75NTR proteolytic pathway and induced p75NTR-dependent behavioral/neuroplasticity changes. CONCLUSION: We thus hypothesize that antidepressants co-opt both BDNF/TrkB and proBDNF/p75NTR systems to induce a more efficient activity-dependent synaptic competition, thereby boosting the brain ability for remodeling.
This article describes the actual problem and the need to develop a methodology/algorithm for working with innovative projects in universities in the face of sanctions pressure. The article discusses ...both theoretical and practical aspects of this problem, and puts forward the idea that universities can act as innovative production units to overcome the negative consequences of sanctions pressure. The implementation of this idea is ensured by creating the necessary favorable organizational, financial, infrastructural and other conditions conducive to the creation and implementation of innovative projects in universities. The role of universities in the innovation ecosystem is considered, including taking into account world experience. The article is based on the latest scientific research in the field of innovation management and proposes to develop a methodology/algorithm for working with innovative projects in universities, from the idea generation stage to successful implementation. It considers issues related to the selection of an innovative project, its financing, planning and management, as well as the interaction between the project team and potential partners and investors. The development of such a methodology can help in the process of generating ideas and successfully implementing innovative projects in universities, which in turn contributes to sustainable economic development.
Genotyping and analysis the drug resistance of 59 isolates of
M. tuberculosis
obtained from patients living in Altai Territory were performed using a BACTEC MGIT 960 fluorometric system by means of ...VNTR typing (variable number tandem repeat), PCR-RFLP analysis, and sequence analysis. The occurrence frequency was highest for isolates of the Beijing family (
n
=30, 50.8%). Analysis of mutation spectrum in the
rpoB
gene associated with rifampicin resistance revealed the major mutation (codon 531 of the
rpoB
gene) in 93% samples, which allows us to use rapid test systems.
The problem of Mycobacterium tuberculosis virulence, together with drug resistance, is becoming key for the design of drugs with a new mechanism of action and the production of modern concepts and ...tuberculosis treatment schemes. The review describes gene complexes and their products, including mycolic acids and global regulatory systems at the level of transcriptional, translational, and post-translational modification, etc. The criteria for selection of virulence/pathogenicity factors that might be used for comparative genomic analysis of strains differing in the degree of virulence were recommended. The experimental approaches and test systems for an adequate estimation of the virulence degree of different strains of M. tuberculosis were analyzed.
The results of recent (10-12 years) research in the functions of two-gene chromosomal modules are considered and generalized. One of the genes encodes a toxin protein; the product of the other gene ...is an antitoxin protein. In the course of balanced bacterial growth, the toxin is constantly neutralized by the antitoxin; however, certain metabolic changes (amino acid starvation, etc.) disturb the balance and then the toxin “poisons” the cell (in most cases, by destroying mRNA). As a result, bacterial growth ceases. In accordance with one group of the data, long-term inhibition of growth of most cells results in their programmed death and destruction, corresponding to apoptosis; this allows a minor part of the population to survive due to an additional nutrient source. The results of other works show that growth inhibition is mostly reversible and the functions of the relevant gene modules are restricted to the regulation of cell metabolism, i.e., transition of bacteria to the hypometabolic state. There is also a compromise point of view. The possibilities of biotechnological applications for “toxin-antitoxin” systems are discussed.
A standard procedure for characterizing the high-purity germanium detector (HPGe), manufactured by Canberra Industries Inc., is performed directly by the company using patented methods. However, the ...procedure is usually expensive and must be repeated because the characteristics of the HPGe crystal changes over time. In this work, the principles of a technique for use in obtaining and optimizing the detector characteristics based on a cost-effective procedure in a standard research laboratory were developed. The technique required the geometrical parameters of the detector to be determined as precisely as possible by the Monte Carlo method in parallel with the optimization process based on evolutionary algorithms. The development of this approach facilitated the modeling of the HPGe detector as a standardized procedure. The results would be also beneficial in the development of gamma spectrometers and/or their calibrations before routine measurements.
•HPGe characteristics were obtained and optimized using a cost-effective procedure.•Geometry parameters of HPGe were determined using Monte Carlo simulation (MC).•Method of evolutionary algorithms was used for optimization in parallel with MC.•Results of this study can be used in both spectrometer development and calibration.
New monotypic genera are established for African Lasiocampidae: Hecata gen. n. (type species Megasoma splendens Druce, 1887), Selena gen. n. (type species Megasoma vesta Druce, 1887), Tragoptyssa ...gen. n. (type species Streblote flavimaculata Tams, 1929), Ammacosola gen. n. (type species Beralade pygmula Strand, 1911), Scythropa gen. n. (type species Pseudometa schultzei Aurivillius, 1905), and Cryptopacha gen. n. (type species Metanastria porphyria Holland, 1893), as well as Pellecebra gen. n. for the new species Pellecebra superba sp. n. (type locality is the Democratic Republic of the Congo). New species combinations are also introduced, and new synonymy is established: Pseudometa schultzei Aurivillius, 1905 = Pseudometa scythropa Hering, 1928, syn. n.
The review considers papers published over the last 15 years that deal with the presence in cells of some bacterial genera and species of a second chromosome that is smaller than the main one ...(occasionally, of two additional chromosomes). These additional chromosomes differ from the main one in the set of genes and specific features of replication; however, they carry genes vitally important for the bacterium. The role of these chromosomes and their probable origin from megaplasmids are discussed.
It is shown that, with the help of adsorption–catalytic deformation, it is possible to significantly change the composition of the skeletal nickel hydrogenation catalyst by changing the steric factor ...directly under the conditions of the chemical reaction. Various substances were tested as model compounds undergoing reduction: hydrogen peroxide, sodium maleate, and propen-2-ol-1. It is shown that, during the hydrogenation reaction, as a result of strong local overheating, the catalyst grain is deformed and the aluminum atoms that were previously in the bulk of this grain appear on the surface, after which aluminum becomes available for further leaching, while yielding additional hydrogen.
