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Tailocins are nanomolecular machines with bactericidal activity. They are produced by bacteria to contribute to fitness in mixed communities, and hence, they play a critical role in their ecology in a variety of habitats. Here, we characterized the new tailocin produced by Dickeya dadantii strain 3937, a well-characterized member of plant pathogenic Soft Rot Pectobacteriaceae (SRP). Tailocins induced in D. dadantii were ca. 166 nm long tubes surrounded by contractive sheaths with baseplates having tail fibers at one end. A 22-kb genomic cluster involved in their synthesis and having high homology to the cluster coding for the tail of the Peduovirus P2 was identified. The D. dadantii tailocins, termed dickeyocins P2D1 (phage P2-like dickeyocin 1), were resistant to inactivation by pH (3.5-12), temperature (4-50°C), and elevated osmolarity (NaCl concentration: 0.01-1 M). P2D1 could kill a variety of different Dickeya spp. but not any strain of Pectobacterium spp. tested and were not toxic to Caenorhabditis elegans. [ABSTRACT FROM AUTHOR]

Background: Statins and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are cornerstones of therapy to prevent cardiovascular disease, acting by lowering lipid concentrations and only partially identified pleiotropic effects. This study aimed to analyze impacts of atorvastatin and synthetic peptide PCSK9i on bioenergetics and function of microvascular endothelial cells and cardiomyocytes. Methods: Mitochondrial function and abundance as well as intracellular nucleotides, membrane potential, cytoskeleton structure, and cell proliferation rate were evaluated in mouse heart microvascular endothelial cells (H5V) and cardiomyocytes (HL-1) under normal and hypoxia-mimicking conditions (CoCl2 exposure). Results: In normal conditions PCSK9i, unlike atorvastatin, enhanced mitochondrial respiratory parameters, increased nucleotide levels, prevented actin cytoskeleton disturbances and stimulated endothelial cell proliferation. Under hypoxia-mimicking conditions both atorvastatin and PCSK9i improved the mitochondrial respiration and membrane potential in both cell types. Conclusion: This study demonstrated that both treatments benefited the endothelial cell and cardiomyocyte bioenergetics, but the effects of PCSK9i were superior. [ABSTRACT FROM AUTHOR]

SeqA protein, a main negative regulator of the replication initiation of the Escherichia coli chromosome, also has several other functions which are still poorly understood. It was demonstrated previously that in seqA mutants the copy number of another replicon, the [lambda] plasmid, is decreased, and that the activity of the [lambda] [p.sub.R] promoter (whose function is required for stimulation of ori[lambda]) is lower than that in the wild-type host. Here, SeqA-mediated regulation of [lambda] phage and plasmid replicons was investigated in more detail. No significant influence of SeqA on ori[lambda]-dependent DNA replication in vitro was observed, indicating that a direct regulation of [lambda] DNA replication by this protein is unlikely. On the other hand, density-shift experiments, in which the fate of labelled [lambda] DNA was monitored after phage infection of host cells, strongly suggested the early appearance of [sigma] replication intermediates and preferential rolling-circle replication of phage DNA in seqA mutants. The directionality of [lambda] plasmid replication in such mutants was, however, only slightly affected. The stability of the heritable [lambda] replication complex was decreased in the seqA mutant relative to the wild-type host, but a stable fraction of the [lambda] O protein was easily detectable, indicating that such a heritable complex can function in the mutant. To investigate the influence of seqA gene function on heritable complex- and transcription-dependent [lambda] DNA replication, the efficiency of [lambda] plasmid replication in amino acid-starved relA seqA mutants was measured. Under these conditions, seqA dysfunction resulted in impairment of [lambda] plasmid replication. These results indicate that unlike oriC, SeqA modulates [lambda] DNA replication indirectly, most probably by influencing the stability of the [lambda] replication complex and the transcriptional activation of ori[lambda].

Floral morphological adaptations and composition of secretions aim to ensure reproductive success. Maxillariella is part of the largest subtribe of Orchidaceae, and Maxillariella spp. are important components of the orchid flora of the Neotropics. The aim of this paper was to provide a detailed study of the reproductive biology of three morphologically and geographically distinct species: M. sanguinea , M. variabilis and M. vulcanica. For many years, species in this group were considered rewardless, but several studies have revealed that lips of some species may secrete resins. However, most published research has mainly focused on investigating either micromorphology (SEM, TEM, histochemistry) or fragrance composition (GC–MS). In this study, we make the first attempt to investigate Maxillariella flowers in a more comparative manner by combining both aspects. In all investigated species we reported the presence of resins with lipids, sugars and/or proteins, suggesting a potential role as a food reward. Scant quantities of residues indicate that they are produced periodically in small quantities. Chemical analysis revealed significant differences between species, however, the presence of some compounds was constant. Cycloartenal and cycloartenol (main ingredients of resin and wax-like material in some Maxillariinae) were not been found. [ABSTRACT FROM AUTHOR]

Abstract Background Mucopolysaccharidoses (MPS) are severe metabolic disorders caused by accumulation of undegraded glycosaminoglycans (GAGs) in lysosomes due to defects in certain lysosomal hydrolases. Substrate reduction therapy (SRT) has been proposed as one of potential treatment procedures of MPS. Importantly, small molecules used in such a therapy might potentially cross the blood–brain barrier (BBB) and improve neurological status of patients, as reported for a natural isoflavone, 5, 7-dihydroxy-3- (4-hydroxyphenyl)-4 H-1-benzopyran-4-one, also known as genistein. Although genistein is able to cross BBB to some extent, its delivery to the central nervous system is still relatively poor (below 10% efficiency). Thus, we aimed to develop a set of synthetically modified genistein molecules and characterize physicochemical as well as biological properties of these compounds. Methods Following parameters were determined for the tested synthetic derivatives of genistein: cytotoxicity, effects on cell proliferation, kinetics of GAG synthesis, effects on epidermal growth factor (EGF) receptor’s tyrosine kinase activity, effects on lysosomal storage, potential ability to cross BBB. Results We observed that some synthetic derivatives inhibited GAG synthesis similarly to, or more efficiently than, genistein and were able to reduce lysosomal storage in MPS III fibroblasts. The tested compounds were generally of low cytotoxicity and had minor effects on cell proliferation. Moreover, synthetic derivatives of genistein revealed higher lipophilicity (assessed in silico) than the natural isoflavone. Conclusion Some compounds tested in this study might be promising candidates for further studies on therapeutic agents in MPS types with neurological symptoms.