Inhibitors of dipeptidyl-peptidase-4: obvious and probable (literature review)

The purpose of the presented literature review was an attempt to sum up current estimates of the effect of the use of dipeptidyl peptidase-4 inhibitors (iDPP-4) in the algorithms of both traditional (diabetes mellitus) and a number of alternative nosologies, in particular, oncological and neurological pathology, as well as a new coronavirus infection (COVID-19). To do this, the most large-scale (as a rule) publications of 2018–2021 devoted to the problems under consideration were analyzed. The search was carried out by keywords in the Pubmed information base (ncbi.nlm.nih.gov). Factors contributing to the widespread use of IDP-4 in clinical practice are both pharmacologically clear mechanism of action and efficacy, as well as the possibility of oral use, a successful pharmacokinetic profile, low toxicity, in particular, a low risk of hypoglycemia. Newly obtained data on the mechanisms of mechanisms are discussed. Renoprotective action, the presence of cardioprotection is debated. The biochemical prerequisites for the possible effectiveness of iDPP-4 as blockers of the development of a hyperimmune reaction that causes, in particular, the severe course of the new coronavirus infection are discussed. At the same time, the results of studies of various designs are categorically compared, indicating both in favor of the use of iDPP-4 in patients with COVID-19, and not noticing its expediency. It is concluded that, given the large-scale biochemical role of DPP-4, it is important both to continue the active use of its inhibitors in diabetes mellitus, and to expand attempts to use them in a number of other nosologies, including COVID-19

Longitudinal spin transport in diluted magnetic semiconductor superlattices: the effect of the giant Zeeman splitting

Longitudinal spin transport in diluted magnetic semiconductor superlattices is investigated theoretically. The longitudinal magnetoconductivity (MC) in such systems exhibits an oscillating behavior as function of an external magnetic field. In the weak magnetic field region the giant Zeeman splitting plays a dominant role which leads to a large negative magnetoconductivity. In the strong magnetic field region the MC exhibits deep dips with increasing magnetic field. The oscillating behavior is attributed to the interplay between the discrete Landau levels and the Fermi surface. The decrease of the MC at low magnetic field is caused by the $s-d$ exchange interaction between the electron in the conduction band and the magnetic ions.Comment: 6 pages, 9 figures, submitted to Phys. Rev.

Recombination Phenotypes of Escherichia coli greA Mutants

<p>Abstract</p> <p>Background</p> <p>The elongation factor GreA binds to RNA polymerase and modulates transcriptional pausing. Some recent research suggests that the primary role of GreA may not be to regulate gene expression, but rather, to promote the progression of replication forks which collide with RNA polymerase, and which might otherwise collapse. Replication fork collapse is known to generate dsDNA breaks, which can be recombinogenic. It follows that GreA malfunction could have consequences affecting homologous recombination.</p> <p>Results</p> <p><it>Escherichia coli </it>mutants bearing substitutions of the active site acidic residues of the transcription elongation factor GreA, D41N and E44K, were isolated as suppressors of growth inhibition by a toxic variant of the bacteriophage lambda Red-beta recombination protein. These mutants, as well as a D41A <it>greA </it>mutant and a <it>greA </it>deletion, were tested for proficiency in recombination events. The mutations were found to increase the efficiency of RecA-RecBCD-mediated and RecA-Red-mediated recombination, which are replication-independent, and to decrease the efficiency of replication-dependent Red-mediated recombination.</p> <p>Conclusion</p> <p>These observations provide new evidence for a role of GreA in resolving conflicts between replication and transcription.</p

Characteristic of bacteriurii in patients with urinary infections, living in different regions

The aim of the research is to give comparative characteristics of bacteriurii and microflora sensitiveness to antibiotics in persons suffering from urinary infections (two regions, Moscow and Tyumen) Material and methods of research: 173 patients with urinary infection (cystitis, pyelonephritis) were examined. Material for research was media portion of freely produced urine.The investigation of bacteriurii was carried out with quantitative method according to recommendations of National Committee on Clinic Laboratory Standards (NCCLS, USA) The results obtained and discussion It is shown that E. coli and Enterococus were most frequently in persons living in Tyumen. E. Coli and K. pneumomiae were revealed in Moscow. The most active preparation against E. coli Tyumen inhabitants were nitrofuranam, karbopenemy, cefalosporiny of III generation and less important aminoglikozidy, against Enterococcus — ftorkhinoly, vancomicin, Laevomycetin. In patients with infections urinary infections in Moscow the most active preparations against E. coli and К pneumomiae were Karbopenemy, aminoglikozidy and cefalosporiny of III generation and ftorkhinoly. High resistance to Nitrofuranam was marked (= 62 percents). Conclusion. Bacteriuriii features were revealed in patients with the urinary infections ways in different regions of the Russian Federation. The most active preparations which can be used for the treatment of patients with urinary infections taking into account the exciters given were shown on resistance.Цель работы — дать сравнительную характеристику бактерийурии и чувствительности микрофлоры к антибиотикам у жителей двух регионов (г. Москва и г. Тюмень), страдающих инфекциями мочевыводящих путей. Материал и методы исследования: всего обследовано 173 больных с инфекцией мочевыводящих путей (цистит, пиелонефрит). Материалом для исследования была средняя порция свободно выпущенной мочи. Исследование бактерийурии проводилось количественным методом согласно рекомендациям Национального комитета по клиническим лабораторным стандартам (NCCLS, США). Полученные результаты и обсуждение. Показано, что у жителей г. Тюмени наиболее часто выделяются из мочи E.Coli и Enterococcus, а в г. Москве — Е. Coli и К. pneumoniae. Наиболее активными препаратами в отношении Е. СоМ у больных в г. Тюмени являлись нитрофураны, карбопенемы, цефалоспорины III поколения и, в меньшей степени, аминогликозиды; в отношении Enterococcus — фторхинолоны, ванкомицин и левомицетин (хлорамфеникол). У больных с инфекцией мочевыводящих путей в г. Москве наиболее активными препаратами в отношении Е. Coli и К. pneumoniae оказались карбопенемы, аминогликозиды и цефалоспорины III поколения, а также фторхинолоны. При этом к нитрофуранам в случае выделения К. pneumoniae отмечалась высокая резистентность (почти 62%). Заключение. Проведенные исследования выявили особенности бактерийурии у больных с инфекциями мочевыводящих путей в различных регионах РФ, а также показали наиболее активные препараты, которые могут быть использованы для лечения больных с учетом данных по локальной резистентности возбудителей

A Reduction in Ribonucleotide Reductase Activity Slows Down the Chromosome Replication Fork but Does Not Change Its Localization

BACKGROUND:It has been proposed that the enzymes of nucleotide biosynthesis may be compartmentalized or concentrated in a structure affecting the organization of newly replicated DNA. Here we have investigated the effect of changes in ribonucleotide reductase (RNR) activity on chromosome replication and organization of replication forks in Escherichia coli. METHODOLOGY/PRINCIPAL FINDINGS:Reduced concentrations of deoxyribonucleotides (dNTPs) obtained by reducing the activity of wild type RNR by treatment with hydroxyurea or by mutation, resulted in a lengthening of the replication period. The replication fork speed was found to be gradually reduced proportionately to moderate reductions in nucleotide availability. Cells with highly extended C periods showed a "delay" in cell division i.e. had a higher cell mass. Visualization of SeqA structures by immunofluorescence indicated no change in organization of the new DNA upon moderate limitation of RNR activity. Severe nucleotide limitation led to replication fork stalling and reversal. Well defined SeqA structures were not found in situations of extensive replication fork repair. In cells with stalled forks obtained by UV irradiation, considerable DNA compaction was observed, possibly indicating a reorganization of the DNA into a "repair structure" during the initial phase of the SOS response. CONCLUSION/SIGNIFICANCE:The results indicate that the replication fork is slowed down in a controlled manner during moderate nucleotide depletion and that a change in the activity of RNR does not lead to a change in the organization of newly replicated DNA. Control of cell division but not control of initiation was affected by the changes in replication elongation

Natural Killer Lysis Receptor (NKLR)/NKLR-Ligand Matching as a Novel Approach for Enhancing Anti-Tumor Activity of Allogeneic NK Cells

NK cells are key players in anti tumor immune response, which can be employed in cell-based therapeutic modalities. One of the suggested ways to amplify their anti tumor effect, especially in the field of stem cell transplantation, is by selecting donor/recipient mismatches in specific HLA, to reduce the inhibitory effect of killer Ig-like receptors (KIRs). Here we suggest an alternative approach for augmentation of anti tumor effect of allogeneic NK cells, which is founded on profile matching of donor NK lysis receptors (NKLR) phenotype with tumor lysis-ligands.We show that an NKLR-mediated killing directly correlates with the NKLR expression intensity on NK cells. Considerable donor variability in the expression of CD16, NKp46, NKG2D and NKp30 on circulating NK cells, combined with the stability of phenotype in several independently performed tests over two months, indicates that NKLR-guided selection of donors is feasible. As a proof of concept, we show that melanoma cells are dominantly recognized by three NKLRs: NKG2D, NKp30 and NKp44. Notably, the expression of NKp30 on circulating NK cells among metastatic melanoma patients was significantly decreased, which diminishes their ability to kill melanoma cells. Ex vivo expansion of NK cells results not only in increased amount of cells but also in a consistently superior and predictable expression of NKG2D, NKp30 and NKp44. Moreover, expanded NK cultures with high expression of NKG2D or NKp30 were mostly derived from the corresponding NKG2D(high) or NK30(high) donors. These NK cultures subsequently displayed an improved cytotoxic activity against melanoma in a HLA/KIR-ligand mismatched setup, which was NKLR-dependent, as demonstrated with blocking anti-NKG2D antibodies.NKLR/NKLR-ligand matching reproducibly elicits enhanced NK anti-tumor response. Common NKLR recognition patterns of tumors, as demonstrated here in melanoma, would allow implementation of this approach in solid malignancies and potentially in hematological malignancies, either independently or in adjunction to other modalities

Semiconductor Spintronics

Spintronics refers commonly to phenomena in which the spin of electrons in a solid state environment plays the determining role. In a more narrow sense spintronics is an emerging research field of electronics: spintronics devices are based on a spin control of electronics, or on an electrical and optical control of spin or magnetism. This review presents selected themes of semiconductor spintronics, introducing important concepts in spin transport, spin injection, Silsbee-Johnson spin-charge coupling, and spindependent tunneling, as well as spin relaxation and spin dynamics. The most fundamental spin-dependent nteraction in nonmagnetic semiconductors is spin-orbit coupling. Depending on the crystal symmetries of the material, as well as on the structural properties of semiconductor based heterostructures, the spin-orbit coupling takes on different functional forms, giving a nice playground of effective spin-orbit Hamiltonians. The effective Hamiltonians for the most relevant classes of materials and heterostructures are derived here from realistic electronic band structure descriptions. Most semiconductor device systems are still theoretical concepts, waiting for experimental demonstrations. A review of selected proposed, and a few demonstrated devices is presented, with detailed description of two important classes: magnetic resonant tunnel structures and bipolar magnetic diodes and transistors. In most cases the presentation is of tutorial style, introducing the essential theoretical formalism at an accessible level, with case-study-like illustrations of actual experimental results, as well as with brief reviews of relevant recent achievements in the field.Comment: tutorial review; 342 pages, 132 figure