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Bacterial communities of Antarctic lichens explored by gDNA and cDNA 16S rRNA gene amplicon sequencing
Get PDFRecently, lichens came once more into the scientific spotlight due to their unique relations with prokary otes. Sever al temper ate re gion lichen species have been thoroughly explored in this regard yet, the information on Antarctic lichens and their associated bacterio- biomes is somewhat lacking. In this paper, we assessed the phylogenetic structure of the whole and acti v e fractions of bacterial com- munities housed by Antar ctic lic hens growing in differ ent envir onmental conditions by targeted 16S rRNA gene amplicon sequencing. Bacterial communities associated with lichens pr ocur ed fr om a nitr ogen enriched site wer e v er y distinct fr om the comm unities iso- lated from lichens of a nitrogen depleted site. The former were characterized by substantial contributions of Bacteroidetes phylum members and the elusi v e Armatimonadetes. At the nutrient-poor site the lichen-associated bacteriobiome structur e w as unique for eac h lic hen species, with c hlorolic hens being occupied largely by Proteobacteria. Lichen species with a pronounced discrepancy in di v ersity between the whole and acti v e fractions of their bacterial communities had the widest ecological amplitude, hinting that the nonacti v e part of the comm unity is a r eserv oir of latent str ess coping mechanisms. This is the first investigation to make use of targeted metatranscriptomics to infer the bacterial biodi v ersity in Antarctic lichens
Apoptotic Factors Are Evolutionarily Conserved Since Mitochondrial Domestication
Get PDFThe mechanisms initiating apoptotic programmed cell death in diverse eukaryotes are very similar. Basically, the mitochondrial permeability transition activates apoptotic proteases, DNases, and flavoproteins such as apoptosis-inducing factors (AIFs). According to the hypothesis of the endosymbiotic origin of apoptosis, these mechanisms evolved during mitochondrial domestication. Various phylogenetic analyses, including ours, have suggested that apoptotic factors were eubacterial protomitochondrial toxins used for killing protoeukaryotic hosts. Here, we tested whether the function of yeast Saccharomyces cerevisiae apoptotic proteases (metacaspases Mca1 and Nma111), DNase Nuc1, and flavoprotein Ndi1 can be substituted with orthologs from remotely related eukaryotes such as plants, protists, and eubacteria. We found that orthologs of remotely related eukaryotic and even eubacterial proteins can initiate apoptosis in yeast when triggered by chemical stresses. This observation suggests that apoptotic mechanisms have been maintained since mitochondrial domestication, which occurred approximately 1,800 Mya. Additionally, it supports the hypothesis that some of these apoptotic factors could be modified eubacterial toxins
Impairment of the non-catalytic subunit Dpb2 of DNA Pol ε results in increased involvement of Pol δ on the leading strand
Get PDFThe generally accepted model assumes that leading strand synthesis is performed by Pol ε, while lagging-strand
synthesis is catalyzed by Pol δ. Pol ε has been shown to target the leading strand by interacting with the CMG
helicase [Cdc45 Mcm2–7 GINS(Psf1–3, Sld5)]. Proper functioning of the CMG-Pol ε, the helicase-polymerase
complex is essential for its progression and the fidelity of DNA replication. Dpb2p, the essential non-catalytic subunit of Pol ε plays a key role in maintaining the correct architecture of the replisome by acting as a link between Pol ε and the CMG complex. Using a temperature-sensitive dpb2–100 mutant previously isolated in our laboratory, and a genetic system which takes advantage of a distinct mutational signature of the Pol δ-L612M variant which allows detection of the involvement of Pol δ in the replication of particular DNA strands we show that in yeast cells with an impaired Dpb2 subunit, the contribution of Pol δ to the replication of the leading strand is significantly increased
Keratin-Butyrate Scaffolds Promote Skin Wound Healing in Diabetic Rats Through Down-Regulation of IL-1β and Up-Regulation of Keratins 16 and 17
Get PDFDimeric Benzodiazepines as Peptide Mimetics to Overcome p53-Dependent Drug Resistance of Tumors
Get PDF: Benzodiazepines that consist of one α- and one β-amino acid residues linked together in a
seven-membered heterocyclic ring could be treated as small, rigid, cyclic dipeptides capable of exhibiting a wide range of biological activities. During our research on novel analogues of anthramycin,
a tricyclic antibiotic benzodiazepine, we developed the synthesis of two benzodiazepine dimers,
obtained through the cyclization of appropriate linear tripeptides. The synthesized compounds were
tested on a panel of seven cancer and normal cell lines. The developed molecules exhibited promising cytotoxic activity against the lung cancer cell lines A549 and NCI-H1299 and the epidermoid
carcinoma cell line A-431. Moreover, they showed significant selectivity compared to the reference
cell lines (BJ—human normal skin fibroblasts and MRC-5—human normal lung cell line). When
tested on two isogenic cell lines, HCT116 and HCT116p53−/− (colon cancer), contrary to cisplatin
being used as a positive control, the obtained compounds showed a cytotoxic effect independent
of the p53 protein status. For the above reasons, the obtained compounds can be considered a new
group of promising anticancer agents, useful in the fight against p53-dependent drug resistance in
cancers. They can also be treated as convenient, leading structures suitable for further optimization
and searching for more active and selective molecules
Contamination of aquatic environment with anticancer reagents influences Daphnia magna – Ecotoxicogenomics approach
Get PDFPharmaceuticals used in human medicine contaminate freshwater ecosystems. Chemotherapeutics applied in cancer treatment are found in freshwaters at low concentrations (in the range of ng L-1) which, however, can be toxic or mutagenic to aquatic organisms. The aim of this study was to determine the impact of the alkylating/crosslinking anticancer agents, cyclophosphamide (CP) and cisplatin (CDDP), at the concentration detected in water, on Daphnia magna life history, transcriptome, and proteome. This filter feeding cladoceran is an important member of the aquatic food webs controlling algal biomass and forming basic food for planktivorous fish. Here, observations of the D. magna growth rate, age at first reproduction, and the number of eggs produced were performed in the presence of CP or CDDP. The D. magna proteins and RNA were isolated and analysed by mass spectrometry and the mRNA-seq method, respectively. Five generations of contact with the pharmaceuticals in question significantly influenced the D. magna life history parameters with the growth rate and number of laid eggs decreased, whereas age at first reproduction was increased. A decrease in survivorship was observed when daphnids were exposed to CP. These changes are the result of modifications in the gene/transcript expression followed by differences in the proteome profile in comparison to the untreated control. The proteome changes were generally in accordance with the modified transcriptome. The ecotoxicogenomics approach makes it possible to get closer to a complete picture of the influence of CP and CDDP on Daphnia. We have gathered evidence that animals in the presence of anticancer pharmaceuticals attempt to cope with permanent stress by changing their proteome and transcriptome profile. Additionally, our analyses indicate that CDDP showed a stronger effect on tested organisms than CP
Synthesis and applications of cyclonucleosides: an update (2010–2023)
Get PDFCyclonucleosides are a group of nucleoside derivatives which, in addition to the classical N-glycosidic bond, have an additional covalent bond (linker, bridge) in their structure, which connects the heterocyclic base and sugar ring. The majority of them have been discovered in the laboratory; however, few such compounds have also been found in natural sources, including metabolites of sponges or radical damage occurring in nucleic acids. Due to their structural properties—rigid, fixed conformation—they have found wide applications in medicinal chemistry and biochemistry as biocides as well as enzyme inhibitors and molecular probes. They have also found use as convenient synthetic tools for the preparation of new nucleoside analogues, enabling structural modifications of both the sugar ring and heterocyclic base. This review summarizes the recent progress in the synthesis of various purine and pyrimidine cyclonucleosides using diverse chemical approaches based on radical, “click”, metal-mediated, and other types of reactions. It also presents recent reports concerning possible applications in medicinal chemistry, as well as their applications as valuable key intermediates in the synthesis of sugar- and base-modified nucleoside analogues and heterocyclic compounds
Expression of Saccharomyces cerevisiae RER2 Gene Encoding Cis-Prenyltransferase in Trichoderma atroviride Increases the Activity of Secretory Hydrolases and Enhances Antimicrobial Features
Get PDFSome Trichoderma spp. exhibit natural abilities to reduce fungal diseases of plants through their mycoparasitic and antagonistic properties. In this study, we created new Trichoderma atroviride strains with elevated antifungal activity. This effect was achieved by improving the activity of cis-prenyltransferase, the main enzyme in dolichol synthesis, by expressing the RER2 gene from Saccharomyces cerevisiae. Since dolichyl phosphate is the carrier of carbohydrate residues during pro�tein glycosylation, activation of its synthesis enhanced the activities of dolichyl-dependent enzymes,DPM synthase and N-acetylglucosamine transferase, as well as stimulated glycosylation of secretory proteins. Cellulases secreted by the transformants revealed significantly higher levels or activities compared to the control strain. Consequently, the resulting Trichoderma strains were more effective
against the plant pathogens Pythium ultimum
The Presence of Plasmids in Lactococcus lactis IL594 Determines Changes in the Host Phenotype and Expression of Chromosomal Genes
Get PDFThe L. lactis IL594 strain contains seven plasmids (pIL1 to pIL7) and is the parental strain of the plasmid-free L. lactis IL1403, one of the most studied lactic acid bacteria (LAB) strain. The genetic sequences of pIL1 to pIL7 plasmids have been recently described, however the knowledge of global changes in host phenotype and transcriptome remains poor. In the present study, global phenotypic analyses were combined with transcriptomic studies to evaluate a potential influence of plasmidic genes on overall gene expression in industrially important L. lactis strains. High-throughput screening of phenotypes differences revealed pronounced phenotypic differences in favor of IL594 during the metabolism of some C-sources, including lactose and β-glucosides. A plasmids-bearing strain presented increased resistance to unfavorable growth conditions, including the presence of heavy metal ions and antimicrobial compounds. Global comparative transcriptomic study of L. lactis strains revealed variation in the expression of over 370 of chromosomal genes caused by plasmids presence. The general trend presented upregulated energy metabolism and biosynthetic genes, differentially expressed regulators, prophages and cell resistance proteins. Our findings suggest that plasmids maintenance leads to significant perturbation in global gene regulation that provides change in central metabolic pathways and adaptive properties of the IL594 cells
The conserved RNA-binding protein Seb1 promotes cotranscriptional ribosomal RNA processing by controlling RNA polymerase I progression
Get PDFTranscription by RNA polymerase I (RNAPI) represents most of the transcriptional activity in eukaryotic cells and is associated with the production of mature ribosomal RNA (rRNA). As several rRNA maturation steps are coupled to RNAPI transcription, the rate of RNAPI elongation directly influences processing of nascent pre-rRNA, and changes in RNAPI transcription rate can result in alternative rRNA processing pathways in response to growth conditions and stress. However, factors and mechanisms that control RNAPI progression by influencing transcription elongation rate remain poorly understood. We show here that the conserved fission yeast RNA-binding protein Seb1 associates with the RNAPI transcription machinery and promotes RNAPI pausing states along the rDNA. The overall faster progression of RNAPI at the rDNA in Seb1-deficient cells impaired cotranscriptional pre-rRNA processing and the production of mature rRNAs. Given that Seb1 also influences pre-mRNA processing by modulating RNAPII progression, our findings unveil Seb1 as a pause-promoting factor for RNA polymerases I and II to control cotranscriptional RNA processing