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Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder caused by WAS gene mutations resulting in haematopoietic/immune cell defects. Recent studies report accelerated death of WAS platelets and lymphocytes. Data on megakaryocyte (MK) maturation, viability and their possible role in thrombocytopenia development in WAS are limited. In this study we evaluate the MK viability and morphology in untreated, romiplostim-treated WAS patients compared with normal controls. The study included 32 WAS patients and 17 healthy donors. MKs were captured from bone marrow aspirates by surface-immobilized anti-GPIIb-IIIa antibody. Viability (by phosphatidylserine [PS] externalization), distribution by maturation stages and size of MK were determined by light microscopy. MK distribution by maturation stages in patients differed from controls. 40 ± 22% of WAS MKs versus 23 ± 11% of normal MKs were at maturation stage 3 (p = 0.02), whereas 24 ± 20% in WAS and 39 ± 14% in controls had megakaryoblast morphology (p = 0.05). Romiplostim treatment changed the MK maturation stages distribution close to normal. PS-positive (PS+) MK in WAS was significantly higher (21 ± 21%) than in healthy controls (2 ± 4%, p < 0.01). WAS patients with more damaging truncating mutations and higher disease score had higher PS+ MK fraction (Spearman r = 0.6, p < 0.003). We conclude that WAS MKs have increased cell death tendency and changes in maturation pattern. Both could contribute to thrombocytopenia in WAS patients., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Here, we report the complete genome sequence of Streptomyces albus strain INA 01303, which was isolated from the Salt Lake Tambukan (Russia). The genome consists of a linear 6,840,896-nucleotide chromosome. This strain is predicted to produce a range of novel secondary metabolites with antibiotic activity.

The TREX-2 complex is essential for the general nuclear mRNA export in eukaryotes. TREX-2 interacts with the nuclear pore and transcriptional apparatus and links transcription to the mRNA export. However, it remains poorly understood how the TREX-2-dependent nuclear export is connected to the subsequent stages of mRNA trafficking. Here, we show that the PCID2 subunit of Drosophila TREX-2 is present in the cytoplasm of the cell. The cytoplasmic PCID2 directly interacts with the NudC protein and this interaction maintains its stability in the cytoplasm. Moreover, PCID2 is associated with the cytoplasmic mRNA and microtubules. The PCID2 knockdown blocks nuclear export of mRNA and also affects the general mRNA transport into the cytoplasm. These data suggest that PCID2 could be the link between the nuclear TREX-2-dependent export and the subsequent cytoplasmic trafficking of mRNA.

SAGA, the multicomponent complex responsible for acetylation of histone N-terminal lysine residues, is involved in the transcription activation of a wide range of eukaryote genes. SAGA contains a protein module, DUB, which is responsible for histone deubiquitination. In this paper we show that the DUB module may be found within cells independently of SAGA. In the absence of" SAGA, the DUB module may be recruited to the promoters of Pol III-transcribed genes, but not to the Pol II-dependent promoters. The DUB module is required to recruit transcription factor Brfl, a subunit of the Pol III-recruiting TFIIIB complex, to the promoters of Pol III-dependent genes. The DUB-module interacts with Pol III in vivo. The DUB-module is essential for recruiting both TFIIIB complexes and PBP complexes to the promoters of Pol III-dependent genes.

The emergence of drug-resistant strains of pathogenic microorganisms necessitates the creation of new drugs. In order to find new compounds that effectively inhibit the growth of pathogenic bacteria and fungi, we synthesized a set of N 4 -derivatives of cytidine, 2'-deoxycytidine and 5-metyl-2'-deoxycytidine bearing extended N 4 -alkyl and N 4 -phenylalkyl groups. The derivatives demonstrate activity against a number of Gram-positive bacteria, including Mycobacterium smegmatis (MIC = 24-200 μM) and Staphylococcus aureus (MIC = 50-200 μM), comparable with the activities of some antibiotics in medical use. The most promising compound appeared to be N 4 -dodecyl-5-metyl-2'-deoxycytidine 4h with activities of 24 and 48 μM against M. smegmatis and S. aureus, respectively, and high inhibitory activity of 0.5 mM against filamentous fungi that can, among other things, damage works of art, such as tempera painting. Noteworthy, some of other synthesized compounds are active against fungal growth with the inhibitory concentration in the range of 0.5-3 mM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Resistance developed to the majority of drugs used to treat infectious diseases warrants the design of new compounds effective against drug-resistant strains of pathogens. Recently, several groups of modified nucleosides have been synthesized and showed significant antibacterial activity in vitro, but their further studies were difficult to undertake because of their low solubility in aqueous solutions. Nevertheless, new compounds, well soluble in water-organic solutions, were synthesized and found to be more effective in inhibiting the growth of Gram-positive bacteria and mycobacteria. The water-soluble forms of modified nucleosides under study were assumed to be their depot forms. To check the assumption, the compounds were tested for hydrolysis in various media and their molecular docking was performed into the active center of the putative target, Mycobacterium tuberculosis flavin-dependent thymidylate synthase ThyX. Computer modelling showed that the water-soluble analogs do not act as ThyX inhibitors, supporting the assumption of their depot nature. The compounds were resistant to chemical hydrolysis but were hydrolyzed when incubated with porcine liver carboxylesterase, human serum, or Staphylococcus aureus 209P. The results demonstrate that the compounds are most likely depot forms of modified nucleosides.

In this study, the microbial communities of two nests of black garden ants (Lasius niger ) in the hollows of stem branches of old apple trees were found to have similar species compositions: each community contained representatives of three species from the Bacillaceae family and one species of actinomycetes from the genus Streptomyces . In total, four types of bacilli and two actinomycetes were isolated. Actinomycetes were identified as Streptomyces antibioticus -like and Streptomyces sp. None of the bacilli had antibiotic activity, whereas both streptomycetes produced antibiotics that inhibited the growth of Gram-positive bacteria in vitro, including isolates from their community. Antibiotic compounds of S. antibioticus -like strain INA 01148 (Institute of New Antibiotics) were identified as actinomycin D and its closest homologue, actinomycin A. Actinomycins presumably change the microbial community of the ant nest substrate as they act against Gram-positive bacteria and against fungi and Gram-negative bacteria. The antibiotic activity of the isolated Streptomyces sp. INA 01156 is of interest, since the substances produced by this strain inhibit the growth of drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus INA 00761 (MRSA) and vancomycin-resistant strain Leuconostoc mesenteroides VKPM B-4177 (VR) (VKPM-National Collection of Industrial Microorganisms (Russian acronym)).

Because of the spread of drug resistance, it is necessary to look for new antibiotics that are effective against pathogenic microorganisms. The purpose of this study was to analyse the species composition of actinobacteria isolated from the digestive tract of the millipedes Nedyopus dawydoffiae and to determine their antimicrobial properties. Species identification was carried out on the basis of the morphological and culture properties and the sequence of the 16S rRNA gene. Actinobacteria were grown in different liquid media. Antibiotic properties were determined against some Gram-positive and Gram-negative bacteria as well as fungi. Of the 15 isolated strains, 13 have antibiotic activity against Gram-positive bacteria (including methicillin-resistant Staphylococcus aureus -MRSA) and fungi, but there was no antibiotic activity against Gram-negative test strains Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. It was established that antibiotic-producing actinobacteria belong to eight species of the genus Streptomyces . Depending on the nutrient medium, actinobacteria demonstrate different antimicrobial activities. As an example, S. hydrogenans shows that even strains selected in one population differ by the range of antimicrobial activity and the level of biosynthesis. Since the antibiotic production is considered as a feature for species competition in the microbiota community, the variability of antibiotic production among different strains of the same species is an adaptive characteristic for the competition in millipedes' digestive tract community.

mRNA transport from the nucleus to the cytoplasm is an essential step of eukaryotic gene expression. A pre-mRNA molecule undergoes modification, such as 5'-capping, splicing, and 3'-end processing, in the nucleus. The molecule being modified interacts with a large number of proteins and, thus, mRNP particles are formed. The binding of factors involved in nuclear export also occurs during transcription and mRNA processing. We have shown that the functioning of TREX-2, an mRNA export complex, is restricted to the nucleus. We used the method of RNA coprecipitation that enables the selective extraction of RNA-protein complexes from samples to show that the transcription elongation complex TREX interacts with mRNA of the β-tubulin 56D gene over the entire length of the molecule. The capping protein Cbp80 reacted both with the cap structure and with a specific part of the coding mRNA of the β-tubulin 56D gene. The TREX-2 complex that mediates mRNA export from the nucleus to the cytoplasm is bound to the same part of the coding sequence. Thus, we identified a common binding site for all of the complexes under investigation on the mRNA of β-tubulin 56D. Co-immunoprecipitation reactions performed with S2 cell extracts revealed interactions between the components of complexes involved in transcription elongation, maturation, and export of mRNA. The model of molecular folding for the mRNP particle involving the mRNA of β-tubulin 56D has been proposed.

Probiotic strain Bacillus subtilis 534 is the base of sporobacterin, a pharmaceutical. In submerged culture it showed antibiotic activity against many of gram-positive and gram-negative bacteria and fungi. The spectrum of the antimicrobial activity of the culture fluid depended on the.cultivation time and aeration intensity. It was shown that component No. 1 of the antibiotic complex was effective against clinical isolates of Acinetobacter baumannii: 20 out of 24 isolates were susceptible to component No. 1, including 15 strains out of 16 panresistant isolates.