Тоталітарні режими: ідеологічне обґрунтування цілей, форм і методів володарювання

Розглянуто теоретичні аспекти взаємовпливу ідеології та конкретно-історичних форм володарювання на прикладі фашизму і націонал-соціалізму. Проаналізована сутність праворадикальної ідеології, причини її виникнення, форми впливу та можливі загрози у контексті демократичного розвитку.The article researches the theoretical aspects of the mutual influence of an ideology and particular-historical forms of reigning on the Fascism's and the National-Socialism's example. The author analyzes the essence of right- radical ideology, the reasons of its appearance, forms of its influence as well as probable threats in the context of democratic development

LmrR-mediated gene regulation of multidrug resistance in Lactococcus lactis

Multidrug resistance (MDR) in Lactococcus lactis is due to the expression of the membrane ATP-binding cassette (ABC) transporter LmrCD. In the absence of drugs, the transcriptional regulator LmrR prevents expression of the lmrCD operon by binding to its operator site. Through an autoregulatory mechanism LmrR also suppresses its own expression. Although the lmrR and lmrCD genes have their own promoters, primer extension analysis showed the presence of a long transcript spanning the entire lmrR–lmrCD cluster, in addition to various shorter transcripts harbouring the lmrCD genes only. ‘In-gel’ Cu-phenanthroline footprinting analysis indicated an extensive interaction between LmrR and the lmrR promoter/operator region. Atomic force microscopy imaging of the binding of LmrR to the control region of lmrR DNA showed severe deformations indicative of DNA wrapping and looping, while LmrR binding to a fragment containing the lmrCD control region induced DNA bending. The results further suggest a drug-dependent regulation mechanism in which the lmrCD genes are co-transcribed with lmrR as a polycistronic messenger. This leads to an LmrR-mediated regulation of lmrCD expression that is exerted from two different locations and by distinct regulatory mechanisms.

LmrCD is a major multidrug resistance transporter in Lactococcus lactis

When Lactococcus lactis is challenged with drugs it displays a multidrug resistance (MDR) phenotype. In silico analysis of the genome of L. lactis indicates the presence of at least 40 putative MDR transporters, of which only four, i.e. the ABC transporters LmrA, LmrC and LmrD, and the major facilitator LmrP, have been experimentally associated with the MDR. To understand the molecular basis of the MDR phenotype in L. lactis, we have performed a global transcriptome analysis comparing four independently isolated drug-resistant strains of L. lactis with the wild-type strain. The results show a strong and consistent upregulation of the lmrC and lmrD genes in all four strains, while the mRNA levels of other putative MDR transporters were not significantly altered. Deletion of lmrCD renders L. lactis sensitive to several toxic compounds, and this phenotype is associated with a reduced ability to secrete these compounds. Another gene, which is strongly upregulated in all mutant strains, specifies LmrR (YdaF), a local transcriptional repressor of lmrCD that belongs to the PadR family of transcriptional regulators and that binds to the promoter region of lmrCD. These results demonstrate that the heterodimeric MDR ABC transporter LmrCD is a major determinant of both acquired and intrinsic drug resistance of L. lactis.

LmrR Is a Transcriptional Repressor of Expression of the Multidrug ABC Transporter LmrCD in Lactococcus lactis▿

LmrCD is an ABC-type multidrug transporter in Lactococcus lactis. LmrR encodes a putative transcriptional regulator. In a ΔlmrR strain, lmrCD is up-regulated. LmrR binds the promoter region of lmrCD and interacts with drugs that cause lmrCD up-regulation. This suggests that LmrR is a drug-dependent transcriptional regulator of lmrCD expression

Antimicrobial and immunomodulatory activities of PR-39 derived peptides

The porcine cathelicidin PR-39 is a host defence peptide that plays a pivotal role in the innate immune defence of the pig against infections. Besides direct antimicrobial activity, it is involved in immunomodulation, wound healing and several other biological processes. In this study, the antimicrobial- and immunomodulatory activity of PR-39, and N- and C-terminal derivatives of PR-39 were tested. PR-39 exhibited an unexpected broad antimicrobial spectrum including several Gram positive strains such as Bacillus globigii and Enterococcus faecalis. Of organisms tested, only Staphylococcus aureus was insensitive to PR-39. Truncation of PR-39 down to 15 (N-terminal) amino acids did not lead to major loss of activity, while peptides corresponding to the C-terminal part of PR-39 were hampered in their antimicrobial activity. However, shorter peptides were all much more sensitive to inhibition by salt. Active peptides induced ATP leakage and loss of membrane potential in Bacillus globigii and Escherichia coli, indicating a lytic mechanism of action for these peptides. Finally, only the mature peptide was able to induce IL-8 production in porcine macrophages, but some shorter peptides also had an effect on TNF-α production showing differential regulation of cytokine induction by PR-39 derived peptides. None of the active peptides showed high cytotoxicity highlighting the potential of these peptides for use as an alternative to antibiotics

PR-39 is most active in disrupting the membrane potential of <i>B. globigii</i>.

<p>The membrane potential sensitive dye DiSC3(5) was incubated with bacteria until a stable baseline was formed. Fluorescence increase upon addition of peptide was measured at Excitation/Emmission 640/670 nm. Shown are representative curves of:PR-39: 2.5 µM, PR-39(1–26): 2.5 µM; PR-39(1–22): 2.5 µM; PR-39(1–18): 2.5 µM; PR-39(1–15): 5 µM; PR-39(16–39): 10 µM; PR-39(20–39): 20 µM; PR-39 (24–39): 10 µM.</p