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91.
SE Ward HS Kim K Komurov S Mendiratta PL Tsai M Schmolke N Satterly B Manicassamy CV Forst MG Roth A García-Sastre KM Blazewska CE McKenna BM Fontoura MA White 《PloS one》2012,7(8):e39284
Influenza A virus infects 5-20% of the population annually, resulting in ~35,000 deaths and significant morbidity. Current treatments include vaccines and drugs that target viral proteins. However, both of these approaches have limitations, as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance. In consequence additional intervention strategies, that target host factors required for the viral life cycle, are under investigation. Here we employed arrayed whole-genome siRNA screening strategies to identify cell-autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human bronchial epithelial cells. Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation. Pharmacological inhibition of representative targets, RGGT and CHEK1, resulted in significant protection against infection of human epithelial cells by the A/WS/33 virus. In addition, chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain. The observations reported here thus contribute to an expanding body of studies directed at decoding vulnerabilities in the command and control networks specified by influenza virulence factors. 相似文献
92.
Grzyb K Rychłowski M Biegniewska A Skorkowski EF 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2003,134(2):207-213
Creatine kinase (CK, ATP creatine phosphotransferase, EC 2.7.3.2) is an enzyme participating in ATP regeneration, which is the primary source of energy in living organisms. We demonstrated that CK from herring spermatozoa has high activity ( approximately 452 micromol/min/g of fresh semen) and has a different electrophoretic mobility from isoenzymes present in skeletal muscle. In our study, we investigated toxic effect of tributyltin (TBT) on herring spermatozoa using a specific sperm viability kit to observe live and dead sperm cells with a confocal microscope. Treatment of herring spermatozoa with TBT caused a time-dependent decrease of viability: 35% nonviable cells with 5 microM TBT and more than 90% nonviable cells with 10 microM TBT after 6 h exposure. We also monitored CK release from damaged spermatozoa into surrounding medium containing different concentrations of TBT. The higher concentration of TBT was used the more CK release from spermatozoa was observed. We suggest that CK could be a good biomarker of sperm cell membranes degradation in the case when lactate dehydrogenase release from permeabilized cells is not possible for rapid determination of the effect of TBT. 相似文献
93.
Nawrot-Porabka K Jaworek J Leja-Szpak A Szklarczyk J Macko M Kot M Mitis-Musioł M Konturek SJ Pawlik WW 《Regulatory peptides》2007,143(1-3):56-63
Ghrelin, a 28-amino-acid peptide produced predominantly by oxyntic mucosa has been reported to affect the pancreatic exocrine function but the mechanism of its secretory action is not clear. The effects of intraduodenal (i.d.) infusion of ghrelin on pancreatic amylase outputs under basal conditions and following the stimulation of pancreatic secretion with diversion of pancreato-biliary juice (DPBJ) as well as the role of vagal nerve, sensory fibers and CCK in this process were determined. Ghrelin given into the duodenum of healthy rats at doses of 1.0 or 10.0 microg/kg increased pancreatic amylase outputs under basal conditions or following the stimulation of pancreatic secretion with DPBJ. Bilateral vagotomy as well as capsaicin deactivation of sensory fibers completely abolished all stimulatory effects of luminal ghrelin on pancreatic exocrine function. Pretreatment with lorglumide, a CCK(1) receptor blocker, reversed the stimulation of amylase release produced by intraduodenal application of ghrelin. Intraduodenal ghrelin at doses of 1.0 or 10.0 microg/kg increased plasma concentrations of CCK and ghrelin. In conclusion, ghrelin given into the duodenum stimulates pancreatic enzyme secretion. Activation of vagal reflexes and CCK release as well as central mechanisms could be implicated in the stimulatory effect of luminal ghrelin on the pancreatic exocrine functions. 相似文献
94.
Chitosan as a lipid binder: a langmuir monolayer study of chitosan-lipid interactions 总被引:1,自引:0,他引:1
Owing to its distinct chemico-biological properties, chitosan, a cationic biopolymer, offers a great potential in multifarious bioapplications. One such application is as a dietary antilipidemic supplement to be used to reduce obesity/overweight and to lower cholesterol. The lipid-binding efficiency of chitosan, however, remains debatable. Accordingly, in this study we investigated the interactions of chitosan with selected lipids, cholesterol and fatty acids, the latter including saturated (stearic acid) and unsaturated (oleic, linoleic, alpha-linolenic) acids. The experiments were performed with the Langmuir monolayer technique, in which surface pressure-area isotherms were recorded for the lipid monolayers spread on the acetate buffer pH 4.0 subphase in the absence and presence of chitosan. We found that the presence of chitosan in the subphase strongly influenced the shape and location of the isotherms, proving that there existed attractions between chitosan and lipid molecules. The attractions were revealed by changes of the molecular organization of the monolayers. The common feature of these changes was that all the monolayers studied underwent expansion, in each case reaching saturation with increasing chitosan concentration. In agreement with the lipid molecular structures, the highest expansions were observed for the most unsaturated fatty acids, linoleic and alpha-linolenic, the lowest for stearic acid, with oleic acid and cholesterol being the intermediate cases. By contrast, the main distinguishing feature of these changes was that, although none of the monolayers studied changed its state when completely saturated with chitosan, compared to the parent ones the compactness of the monolayers was modified. The solid monolayers of stearic acid and cholesterol were loosened, whereas those of all the unsaturated acids, liquid in nature, were tightened. On the basis of these results we tentatively propose a mechanism of the chitosan action that includes both electrostatic and hydrophobic lipid-chitosan interactions as well as hydrogen bonding between them. 相似文献
95.
Katarzyna Garbacz Sabina Żarnowska Lidia Piechowicz Krystyna Haras 《Current microbiology》2013,66(2):169-173
The aim of this study was to compare the spread of multidrug-resistant (MDR) and methicillin-resistant (MR) staphylococci in healthy dogs and in dogs with evident symptoms of infection. The samples from 172 healthy and 197 infected dogs were examined. The staphylococci were identified with conventional methods and by means of the polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method (MboI). Susceptibility to 15 antibiotics from 10 different antimicrobial classes was tested. Resistance to methicillin was confirmed by the presence of Staphylococcus aureus mecA and S. sciuri mecA genes. Multidrug resistance was defined as resistance to three or more antimicrobial classes. The oral mucosa to be the most frequent site of staphylococcal colonization (55.8 %), followed by nasal cavity (44.2 %), and anus (32.6 %). The prevalence of MDR staphylococci in infected dogs was significantly higher than in the healthy animals (74/137 vs. 34/95, P = 0.006). The MR strains of S. pseudintermedius (2.9 %) originated solely from infected dogs. In contrast, the MR coagulase-negative strains (7.4 %) were isolated solely from healthy dogs. S. aureus strains originated from nasal swabs, MRSA strains were not isolated. MDR staphylococci and MR S. pseudintermedius are more common among infected dogs, but coagulase-negative staphylococci (mostly S. sciuri) seem to be a reservoir of methicillin resistance in healthy dogs. 相似文献
96.
Troutman JM Chehade KA Kiegiel K Andres DA Spielmann HP 《Bioorganic & medicinal chemistry letters》2004,14(19):4979-4982
Three isoprenoid diphosphate analogues of farnesyl diphosphate (FPP) where the diphosphate has been replaced by methylene diphosphonate and the negative charges masked by frangible pivaloyloxymethyl (POM) esters were prepared. Farnesyl methylenediphosphonate is a sub-micromolar substrate for protein farnesyl transferase. The tripivaloyloxymethyl esters of isoprenoid methylenediphosphonate have significantly increased lipophilicity and may act as important farnesyl diphosphate prodrugs. 相似文献
97.
Katarzyna Chojnacka 《World journal of microbiology & biotechnology》2007,23(8):1139-1147
The paper discusses biosorption of Cr(III), Cu(II), Mn(II), Zn(II) and Co(II) to the biomass of Chlorella vulgaris, to produce a biologically bound, concentrated form of microelements. The kinetics of biosorption was described with a pseudo-second
order equation and equilibrium with the Langmuir isotherm. The mechanism of biosorption was identified as cation-exchange
with alkaline metals. Cation-exchange capacity was evaluated as 4.07 meq g−1. The effect of operation conditions, pH and temperature, on biosorption performance was investigated and the best operation
conditions for biosorption were selected (pH 5, temperature 25 °C). The maximum sorption capacity of microelements was determined
in single-metal system at pH 5 and 25 °C: Zn(II) 3.30 meq g−1, Cu(II) 1.77 meq g−1, Co(II) 1.75 meq g−1, Cr(III) 1.74 meq g−1, Mn(II) 0.764 meq g−1. Biosorption experiments were also carried out in multi-metal system. The biomass of C. vulgaris enriched with microelements via the process of biosorption in both single- and multi-metal system was discussed in terms
of preparation of feed supplement for laying hens and piglets. The experiments showed that 1 kg of conventional feed for laying
hens can be supplemented with 0.20 g of the biomass enriched with microelements and for piglets with 0.15 g of the preparation. 相似文献
98.
Ecosystems worldwide are threatened with the extinction of plants and, at the same time, invasion by new species. Plant invasiveness and loss of species can be caused by similar but opposing pressures on the community structures. Arbuscular mycorrhizal fungi (AMF) can have multiple positive effects on plant growth, productivity, health, and stress relief. Many endangered species live in symbiosis with AMF. However, the list of the International Union for Conservation of Nature and Natural Resources (IUCN Red List of Threatened Species) indicates that the mycorrhizal status of most of the threatened species has not been assessed. Rare plants often occur in specialized and also endangered habitats and might utilize specialized or unique AMF. The specificity of any endangered plant to its AMF population has not been investigated. Because most of the current AMF isolates that are available colonize a broad range of plant species, selected inocula could be used to promote growth of endangered plants before the proper and more effective indigenous AMF are characterized. Application of AMF in field sites to protect endangered plants is hardly feasible due to the complexity of plant community structures and the large amount of fungal inocula needed. Endangered plants could, however, be grown as greenhouse cultures together with appropriate fungi, and, at the relevant developmental stage, they could be re-planted into native sites to prevent extinction and to preserve plant community ecology. 相似文献
99.
Kochman M Piekarska K Lawrynowicz-Paciorek M 《Medycyna do?wiadczalna i mikrobiologia》2004,56(4):377-390
The aim of this study was to evaluate reliability of identification and determination of sensitivity to antibiotics and chemotherapeutics of some Gram positive cocci strains in 34 sanitary-epidemiological stations. All laboratories engaged in this study received 3 strains: S. aureus (S. aureus SC+ CF+, resistant to methicillin., or S. aureus SC - CF+, sensitive to methicillin), coagulase-negative staphylococci (S. epidermidis or S. haemolyticus or S. saprophyticus) and Enterococcus sp. (E. faecalis HLAR-positive or E. faecalis HLAR-negative or E. faecium or E. gallinarum). All these strains previously were identified in Department of Bacteriology of National Institute of Hygiene. Of the 68 staphylococci strains tested, 66 isolates were correctly identified. Among the 34 enterococcal strains studied the greatest difficulty in identification was caused by E. gallinarum strain--(8 out of 13 strains were incorrectly recognised). The determination of the sensitivity of the control strains to antibiotics and chemotherapeutic agents, generally was performed correctly in accordance with to the NCCLS and national recommendations. Some incorrect results of the antibiograms were caused by an erroneous interpretation of the zones of inhibition. 相似文献
100.
Unusual proteolysis of the protoxin and toxin from Bacillus thuringiensis. Structural implications 总被引:4,自引:0,他引:4
C T Choma W K Surewicz P R Carey M Pozsgay T Raynor H Kaplan 《European journal of biochemistry》1990,189(3):523-527
Trypsin is shown to generate an insecticidal toxin from the 130-kDa protoxin of Bacillus thuringiensis subsp. kurstaki HD-73 by an unusual proteolytic process. Seven specific cleavages are shown to occur in an ordered sequence starting at the C-terminus of the protoxin and proceeding toward the N-terminal region. At each step, C-terminal fragments of approximately 10 kDa are produced and rapidly proteolyzed to small peptides. The sequential proteolysis ends with a 67-kDa toxin which is resistant to further proteolysis. However, the toxin could be specifically split into two fragments by proteinases as it unfolded under denaturing conditions. Papain cleaved the toxin at glycine 327 to give a 34.5-kDa N-terminal fragment and a 32.3-kDa C-terminal fragment. Similar fragments could be generated by elastase and trypsin. The N-terminal fragment corresponds to the conserved N-terminal domain predicted from the gene-deduced sequence analysis of toxins from various subspecies of B. thuringiensis, and the C-terminal fragment is the predicted hypervariable sequence domain. A double-peaked transition was observed for the toxin by differential scanning calorimetry, consistent with two or more independent folding domains. It is concluded that the N- and C-terminal regions of the protoxin are two multidomain regions which give unique structural and biological properties to the molecule. 相似文献