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991.
Pavel V. Panteleev Ilia A. Bolosov Sergey V. Balandin Tatiana V. Ovchinnikova 《Journal of peptide science》2015,21(2):105-113
β‐Hairpin antimicrobial peptides are among the most potent peptide antibiotics of animal origin. Arenicins, isolated earlier from marine polychaeta lugworm Arenicola marina, belong to a family of β‐hairpin antimicrobial peptides and display a broad spectrum of biological activities. However, despite being potent antimicrobials, arenicins are partially unapplicable as therapeutics as a result of their relatively high cytotoxicity against mammalian cells. In this study, a template‐based approach was used to create therapeutically valuable analogs of arenicin‐1 and identify amino acid residues important for antibacterial and cytotoxic activities of the peptide. The plasmids encoding recombinant analogs were constructed by mutagenesis technique based on inverse PCR amplification of the whole arenicin‐1 expression plasmid. The analogs were produced as a part of the fusion proteins in Escherichia coli. It was shown that an obvious reduction in hemolytic activity without lose of antimicrobial activity can be achieved by a single amino acid substitution in the non‐polar face of the molecule with hydrophilic residues such as serine and arginine. As the result, the selective analog with 50‐fold improved therapeutic index was developed. The circular dichroism spectra demonstrated that the secondary structure of the analog was similar to the natural arenicin‐1 in water solution and sodium dodecyl sulfate micelles but significantly differed in the presence of dodecylphosphocholine micelles mimicking mammalian membranes. Similarly to arenicin‐1, the designed analog killed bacteria via induction of the membrane damage, assessed using the fluorescent dye SYTOX Green uptake. Our results afford molecular insight into mechanism of antimicrobial action of the designed arenicin analogs and their possible clinical application. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
992.
Lipid‐dependent pore formation by antimicrobial peptides arenicin‐2 and melittin demonstrated by their proton transfer activity
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Sergei V. Sychev Sergey V. Balandin Pavel V. Panteleev Leonid I. Barsukov Tatiana V. Ovchinnikova 《Journal of peptide science》2015,21(2):71-76
This work presents a comparative study of proton transfer activity (PTA) of two cationic (+6) antimicrobial peptides, β‐structural arenicin‐2 and α‐helical melittin. A new approach was proposed for the detection of passive proton transfer by using proteoliposomes containing bacteriorhodopsin, which creates a small light‐induced electrochemical proton gradient ?ΔpH. Addition of several nanomoles of the peptides lowers ?ΔpH that is proximately indicative of the pore formation. The quantitative analysis of sigmoidal dependences of ?pH on the peptides concentration was carried out using liposomes prepared from PC, PC/PE, PC/PE/PI and PC/PG. Substitution of PC‐containing liposomes with PE‐containing ones, having negative spontaneous curvature, reduced the PTA of α‐helical melittin and increased that of β‐structural arenicin‐2. This result indicates an essential difference in the pore formation by these peptides. Further increase of PTA in response to arenicin‐2 (in contrast to melittin) was observed in the liposomes prepared from PC/PE/PI. The data analysis leads to the conclusion that PTA is influenced by (i) efficiency of the pore assemblage, which depends on the structure of pore‐forming peptides, and the spontaneous curvature of lipids and (ii) the presence of mobile protons in the polar head groups of phospholipids. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
993.
994.
995.
Luís Eduardo Fernandes Rodrigues da Conceição Margarete Alice Fontes Saraiva Raphael Hermano Santos Diniz Juliana Oliveira Gustavo Dimas Barbosa Florencia Alvarez Lygia Fátima da Mata Correa Hygor Mezadri Mauricio Xavier Coutrim Robson José de Cássia Franco Afonso Candida Lucas Ieso Miranda Castro Rogelio Lopes Brandão 《Journal of industrial microbiology & biotechnology》2015,42(2):237-246
996.
997.
Tatiane Klingelfus Paula Moiana da Costa Marcos Scherer Marta Margarete Cestari 《Genetics and molecular biology》2015,38(4):499-506
Even though aluminum is the third most common element present in the earth''s crust,
information regarding its toxicity remains scarce. It is known that in certain cases,
aluminum is neurotoxic, but its effect in other tissues is unknown. The aim of this
work was to analyze the genotoxic potential of aluminum sulfate in kidney tissue of
the fish Rhamdia quelen after trophic contamination for 60 days.
Sixty four fish were subdivided into the following groups: negative control, 5 mg, 50
mg and 500 mg of aluminum sulfate per kg of fish. Samples of the posterior kidney
were taken and prepared to obtain mitotic metaphase, as well as the comet assay. The
three types of chromosomal abnormalities (CA) found were categorized as chromatid
breaks, decondensation of telomeric region, and early separation of sister
chromatids. The tests for CA showed that the 5 mg/kg and 50 mg/kg doses of aluminum
sulfate had genotoxic potential. Under these treatments, early separation of the
sister chromatids was observed more frequently and decondensation of the telomeric
region tended to increase in frequency. We suggest that structural changes in the
proteins involved in DNA compaction may have led to the decondensation of the
telomeric region, making the DNA susceptible to breaks. Moreover, early separation of
the sister chromatids may have occurred due to changes in the mobility of chromosomes
or proteins that keep the sister chromatids together. The comet assay confirmed the
genotoxicity of aluminum sulfate in the kidney tissue of Rhamdia
quelen at the three doses of exposure. 相似文献
998.
Predicting the impact of increasing carbon dioxide concentration and temperature on seed germination and seedling establishment of African grasses in Brazilian Cerrado
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Ana Paula de Faria Geraldo Wilson Fernandes Marcel Giovanni Costa França 《Austral ecology》2015,40(8):962-973
Global climate changes and biological invasions are environmental disturbances that may interact synergistically, causing loss of biodiversity. As the early stages of development are the most sensitive and easily affected by these constraints, this study investigated the effects of increased carbon dioxide (CO2) and temperature, as forecasted for 2100, on seed germination and early development of three species of invasive African grasses that have gradually replaced landscapes of the Brazilian Cerrado biome. It was observed that these parameters affected percentage and rate of germination in Urochloa brizantha, rate of germination and mean germination time in Urochloa decumbens and accelerated autotrophy acquisition in U. brizantha, U. decumbens and Megathyrsus maximus. Regarding root elongation, all species showed changes in total length, absolute and relative growth rate, but at different stages of development or time intervals, with increased temperature being more significant than increased CO2, probably due to seed reserves still being the main carbon sources at this stage. Taken together, the results indicate that the effects of CO2 and increased temperature are species specific and highlight the greatest potential of U. brizantha to germinate, and of U. decumbens for seedling establishment under these environmental changes. 相似文献
999.
Yumi Ueki Michael A Hadders Melanie B Weisser Isha Nasa Paula SoteloParrilla Lauren E Cressey Tanmay Gupta Emil P T Hertz Thomas Kruse Guillermo Montoya A Arockia Jeyaprakash Arminja Kettenbach Susanne M A Lens Jakob Nilsson 《EMBO reports》2021,22(7)
The shugoshin proteins are universal protectors of centromeric cohesin during mitosis and meiosis. The binding of human hSgo1 to the PP2A‐B56 phosphatase through a coiled‐coil (CC) region mediates cohesion protection during mitosis. Here we undertook a structure function analysis of the PP2A‐B56‐hSgo1 complex, revealing unanticipated aspects of complex formation and function. We establish that a highly conserved pocket on the B56 regulatory subunit is required for hSgo1 binding and cohesion protection during mitosis in human somatic cells. Consistent with this, we show that hSgo1 blocks the binding of PP2A‐B56 substrates containing a canonical B56 binding motif. We find that PP2A‐B56 bound to hSgo1 dephosphorylates Cdk1 sites on hSgo1 itself to modulate cohesin interactions. Collectively our work provides important insight into cohesion protection during mitosis. 相似文献
1000.
Lopes M Goupille O Saint Cloment C Lallemand Y Cumano A Robert B 《Development (Cambridge, England)》2011,138(14):3055-3066
Vessels are primarily formed from an inner endothelial layer that is secondarily covered by mural cells, namely vascular smooth muscle cells (VSMCs) in arteries and veins and pericytes in capillaries and veinules. We previously showed that, in the mouse embryo, Msx1(lacZ) and Msx2(lacZ) are expressed in mural cells and in a few endothelial cells. To unravel the role of Msx genes in vascular development, we have inactivated the two Msx genes specifically in mural cells by combining the Msx1(lacZ), Msx2(lox) and Sm22α-Cre alleles. Optical projection tomography demonstrated abnormal branching of the cephalic vessels in E11.5 mutant embryos. The carotid and vertebral arteries showed an increase in caliber that was related to reduced vascular smooth muscle coverage. Taking advantage of a newly constructed Msx1(CreERT2) allele, we demonstrated by lineage tracing that the primary defect lies in a population of VSMC precursors. The abnormal phenotype that ensues is a consequence of impaired BMP signaling in the VSMC precursors that leads to downregulation of the metalloprotease 2 (Mmp2) and Mmp9 genes, which are essential for cell migration and integration into the mural layer. Improper coverage by VSMCs secondarily leads to incomplete maturation of the endothelial layer. Our results demonstrate that both Msx1 and Msx2 are required for the recruitment of a population of neural crest-derived VSMCs. 相似文献