•Archaeological and molecular analysis of human remains from the Catacomb culture.•Y-chromosome STR analysis revealed that both individuals belonged to haplogroup R1b.•MtDNA analysis revealed the two ...Catacomb males to belong to haplogroups H and N.•There is a possible relationship between the Catacomb and Yamnaya cultures.•Analysis of cultural and historical processes in Europe during the Bronze Age.
After discovering the first kurgans in the steppes, the archaeologists were faced with the need to determine the social status of buried persons and the relationship between people buried within the same necropolis. Archaeology has developed its methods and criteria for assessing the social status of buried persons, such as the size of the burial kurgans, the location of burials in the center or on the periphery of the kurgan, the wealth of implements, etc. With the introduction of paleogenetic methods into archeology, new opportunities for research in this direction are opening up. The analysis of ancient DNA is a tool that allows you not to assume but to establish consanguinity.
This study presents the archaeological and molecular analysis of human remains from the East-Manych variant of the Catacomb culture. Catacomb culture dominated eastern Ukraine and southern Russia in the 3rd millennium BCE. The skeletons were recovered from kurgans of the Ergeninskii kurgan group in Kalmykia (Russia) that were radiocarbon dated the Bronze Age (25th–23rd century BCE). Y-chromosome STR analysis revealed that both individuals belonged to haplogroup R1b. This paternal lineage appears at high frequency in central, western, and northern Europe, and commonly appears among the Yamnaya. Analysis of mitochondrial DNA variation revealed the Catacomb males to belong to haplogroups H and N, respectively, both of which also appeared in the Yamnaya. These genetic data suggest a possible relationship between the Catacomb and Yamnaya cultures and contribute to our understanding of the cultural and historical processes occurring in the steppes of Eastern Europe during the Bronze Age.
Antibiotic resistance is a major public health concern in many countries worldwide. The rapid spread of multidrug-resistant (MDR) bacteria is the main driving force for the development of novel ...non-antibiotic antimicrobials as a therapeutic alternative. Here, we isolated and characterized three virulent bacteriophages that specifically infect and lyse MDR
with K23 capsule type. The phages belonged to the
(vB_KpnP_Dlv622) and
(vB_KpnM_Seu621, KpS8) families and contained highly similar receptor-binding proteins (RBPs) with polysaccharide depolymerase enzymatic activity. Based on phylogenetic analysis, a similar pattern was also noted for five other groups of depolymerases, specific against capsule types K1, K30/K69, K57, K63, and KN2. The resulting recombinant depolymerases Dep622 (phage vB_KpnP_Dlv622) and DepS8 (phage KpS8) demonstrated narrow specificity against
with capsule type K23 and were able to protect
larvae in a model infection with a
multidrug-resistant strain. These findings expand our knowledge of the diversity of phage depolymerases and provide further evidence that bacteriophages and phage polysaccharide depolymerases represent a promising tool for antimicrobial therapy.
The aim of the current work was to evaluate applicability of triacetate cellulose hollow fiber vitrification (HFV) method for cryopreservation of groups of in vitro matured bovine oocytes (12–17 ...oocytes per device). We also attempted to optimize HFV protocol by altering concentration of non-permeating cryoprotectant (sucrose) in vitrification solution and concentration of extracellular Ca2+ by using a calcium-free base medium for preparation of vitrification/rewarming solutions with ethylene glycol (EG) as a single permeating cryoprotectant. Neither of modifications of HFV protocol significantly affected survival or fertilization rates of the vitrified bovine oocytes. Embryo development rates in the vitrification groups were lower than those in the control (31.2% of blastocysts at Day 8 post IVF). Use of vitrification/rewarming solutions with lower Ca2+ concentration and EG did not significantly improve embryo development rates. An increase of sucrose concentration in vitrification solution from 0.5 to 1.0 M significantly improved blastocyst yield on Day 8 post IVF (21.1–23.4% vs 3.1–3.5%; p < 0.05). Obtained results indicated that sufficient dehydration of the oocytes and/or the solution surrounding them in hollow fiber before immersion into liquid nitrogen is an important factor for successful vitrification. Use of HFV method allowed simplification and standardization of vitrification/rewarming procedures. Triacetate cellulose hollow fibers can be used successfully for cryopeservation of groups of in vitro matured bovine oocytes.
The widespread use of antimicrobials causes antibiotic resistance in bacteria. The use of butyric acid and its derivatives is an alternative tactic. This review summarizes the literature on the role ...of butyric acid in the body and provides further prospects for the clinical use of its derivatives and delivery methods to the animal body. Thus far, there is evidence confirming the vital role of butyric acid in the body and the effectiveness of its derivatives when used as animal medicines and growth stimulants. Butyric acid salts stimulate immunomodulatory activity by reducing microbial colonization of the intestine and suppressing inflammation. Extraintestinal effects occur against the background of hemoglobinopathy, hypercholesterolemia, insulin resistance, and cerebral ischemia. Butyric acid derivatives inhibit histone deacetylase. Aberrant histone deacetylase activity is associated with the development of certain types of cancer in humans. Feed additives containing butyric acid salts or tributyrin are used widely in animal husbandry. They improve the functional status of the intestine and accelerate animal growth and development. On the other hand, high concentrations of butyric acid stimulate the apoptosis of epithelial cells and disrupt the intestinal barrier function. This review highlights the biological activity and the mechanism of action of butyric acid, its salts, and esters, revealing their role in the treatment of various animal and human diseases. This paper also discussed the possibility of using butyric acid and its derivatives as surface modifiers of enterosorbents to obtain new drugs with bifunctional action.
Clinical studies indicate that partial agonists of the G-protein-coupled, free fatty acid receptor 1 GPR40 enhance glucose-dependent insulin secretion and represent a potential mechanism for the ...treatment of type 2 diabetes mellitus. Full allosteric agonists (AgoPAMs) of GPR40 bind to a site distinct from partial agonists and can provide additional efficacy. We report the 3.2-Å crystal structure of human GPR40 (hGPR40) in complex with both the partial agonist MK-8666 and an AgoPAM, which exposes a novel lipid-facing AgoPAM-binding pocket outside the transmembrane helical bundle. Comparison with an additional 2.2-Å structure of the hGPR40-MK-8666 binary complex reveals an induced-fit conformational coupling between the partial agonist and AgoPAM binding sites, involving rearrangements of the transmembrane helices 4 and 5 (TM4 and TM5) and transition of the intracellular loop 2 (ICL2) into a short helix. These conformational changes likely prime GPR40 to a more active-like state and explain the binding cooperativity between these ligands.
Phage therapy is now seen as a promising way to overcome the current global crisis in the spread of multidrug-resistant bacteria. However, phages are highly strain-specific, and in most cases one ...will have to isolate a new phage or search for a phage suitable for a therapeutic application in existing libraries. At an early stage of the isolation process, rapid screening techniques are needed to identify and type potential virulent phages. Here, we propose a simple PCR approach to differentiate between two families of virulent
phages (
and
) and eleven genera of virulent
phages (
,
,
,
,
,
,
,
,
,
and
). This assay includes a thorough search of a dataset comprising
(
= 269) and
(
= 480) phage genomes available in the NCBI RefSeq/GenBank database for specific genes that are highly conserved at the taxonomic group level. The selected primers showed high sensitivity and specificity for both isolated DNA and crude phage lysates, which permits circumventing DNA purification protocols. Our approach can be extended and applied to any group of phages, given the large number of available genomes in the databases.
The issue of antibiotic resistance in healthcare worldwide has led to a pressing need to explore and develop alternative approaches to combat infectious diseases. Among these methods, phage therapy ...has emerged as a potential solution to tackle this growing challenge. Virulent phages of the
family, known for their ability to cause lysis of
, a clinically significant pathogen frequently associated with multidrug resistance, have proven to be one of the most effective viruses utilized in phage therapy. In order to utilize phages for therapeutic purposes effectively, a thorough investigation into their physiology and mechanisms of action on infected cells is essential. The use of omics technologies, particularly total RNA sequencing, is a promising approach for analyzing the interaction between phages and their hosts, allowing for the assessment of both the behavior of the phage during infection and the cell's response. This review aims to provide a comprehensive overview of the physiology of the
family, utilizing existing analyses of their total phage transcriptomes. Additionally, it sheds light on the changes that occur in the metabolism of
when infected with virulent bacteriophages, contributing to a deeper understanding of the phage-host interaction.
In light of the ever-increasing number of multidrug-resistant bacteria worldwide, bacteriophages are becoming a valid alternative to antibiotics; therefore, their interactions with host bacteria must ...be thoroughly investigated. Here, we report genome-wide transcriptional changes in a clinical
SA515 strain for three time points after infection with the vB_SauM-515A1 kayvirus. Using an RNA sequencing approach, we identify 263 genes that were differentially expressed (DEGs) between phage-infected and uninfected host samples. Most of the DEGs were identified at an early stage of phage infection and were mainly involved in nucleotide and amino acid metabolism, as well as in cell death prevention. At the subsequent infection stages, the vast majority of DEGs were upregulated. Interestingly, 39 upregulated DEGs were common between the 15th and 30th minutes post-infection, and a substantial number of them belonged to the prophages. Furthermore, some virulence factors were overexpressed at the late infection stage, which necessitates more stringent host strain selection requirements for further use of bacteriophages for therapeutic purposes. Thus, this work allows us to better understand the influence of kayviruses on the metabolic systems of
and contributes to a better comprehension of phage therapy.
The issue of antibiotic resistance in healthcare worldwide has led to a pressing need to explore and develop alternative approaches to combat infectious diseases. Among these methods, phage therapy ...has emerged as a potential solution to tackle this growing challenge. Virulent phages of the Herelleviridae family, known for their ability to cause lysis of Staphylococcus aureus, a clinically significant pathogen frequently associated with multidrug resistance, have proven to be one of the most effective viruses utilized in phage therapy. In order to utilize phages for therapeutic purposes effectively, a thorough investigation into their physiology and mechanisms of action on infected cells is essential. The use of omics technologies, particularly total RNA sequencing, is a promising approach for analyzing the interaction between phages and their hosts, allowing for the assessment of both the behavior of the phage during infection and the cell’s response. This review aims to provide a comprehensive overview of the physiology of the Herelleviridae family, utilizing existing analyses of their total phage transcriptomes. Additionally, it sheds light on the changes that occur in the metabolism of S. aureus when infected with virulent bacteriophages, contributing to a deeper understanding of the phage–host interaction.
Cytoplasmic male sterility (CMS) is a common phenotype in higher plants, that is often associated with rearrangements in mitochondrial DNA (mtDNA), and is widely used to produce hybrid seeds in a ...variety of valuable crop species. Investigation of the CMS phenomenon promotes understanding of fundamental issues of nuclear-cytoplasmic interactions in the ontogeny of higher plants. In the present study, we analyzed the structural changes in mitochondrial genomes of three alloplasmic lines of sunflower (
L.). The investigation was focused on CMS line PET2, as there are very few reports about its mtDNA organization.
The NGS sequencing,
assembly, and annotation of sunflower mitochondrial genomes were performed. The comparative analysis of mtDNA of HA89 fertile line and two HA89 CMS lines (PET1, PET2) occurred.
The mtDNA of the HA89 fertile line was almost identical to the HA412 line (NC_023337). The comparative analysis of HA89 fertile and CMS (PET1) analog mitochondrial genomes revealed 11,852 bp inversion, 4,732 bp insertion, 451 bp deletion and 18 variant sites. In the mtDNA of HA89 (PET2) CMS line we determined 27.5 kb and 106.5 kb translocations, 711 bp and 3,780 bp deletions, as well as, 5,050 bp and 15,885 bp insertions. There are also 83 polymorphic sites in the PET2 mitochondrial genome, as compared with the fertile line.
The observed mitochondrial reorganizations in PET1 resulted in only one new open reading frame formation (
), and PET2 mtDNA rearrangements led to the elimination of
, duplication of
gene and appearance of four new ORFs with transcription activity specific for the HA89 (PET2) CMS line-
,
,
and
.
and
are the
chimeric ORFs, containing transmembrane domains and possibly may impact on mitochondrial membrane potential. So
and
may be the cause for the appearance of the PET2 CMS phenotype, while the contribution of other mtDNA reorganizations in CMS formation is negligible.
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