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1.
Katherine E. Price Giulia Orazi Kathryn L. Ruoff Wesley P. Hebert George A. O’Toole Paul Mastoridis 《PloS one》2015,10(10)
Cystic Fibrosis (CF) is a human genetic disease that results in the accumulation of thick, sticky mucus in the airways, which results in chronic, life-long bacterial biofilm infections that are difficult to clear with antibiotics. Pseudomonas aeruginosa lung infection is correlated with worsening lung disease and P. aeruginosa transitions to an antibiotic tolerant state during chronic infections. Tobramycin is an aminoglycoside currently used to combat lung infections in individuals with CF. While tobramycin is effective at eradicating P. aeruginosa in the airways of young patients, it is unable to completely clear the chronic P. aeruginosa infections in older patients. A recent report showed that co-addition of tobramycin and mannitol enhanced killing of P. aeruginosa grown in vitro as a biofilm on an abiotic surface. Here we employed a model system of bacterial biofilms formed on the surface of CF-derived airway cells to determine if mannitol would enhance the antibacterial activity of tobramycin against P. aeruginosa grown on a more clinically relevant surface. Using this model system, which allows the growth of robust biofilms with high-level antibiotic tolerance analogous to in vivo biofilms, we were unable to find evidence for enhanced antibacterial activity of tobramycin with the addition of mannitol, supporting the observation that this type of co-treatment failed to reduce the P. aeruginosa bacterial load in a clinical setting. 相似文献
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Sabrina Locatelli Kurt A. McKean Paul R. Sesink Clee Mary Katherine Gonder 《International journal of primatology》2014,35(2):349-375
Examining how pathogens cross species boundaries, spread within species, and persist within their hosts is an essential part of understanding the factors that underpin the evolution of virulence and host resistance. Here, we review current knowledge about the genetic diversity, molecular epidemiology, prevalence, and pathogenicity of simian immunodeficiency viruses (SIVs). SIVs have crossed species boundaries from simian hosts to humans on at least 12 separate occasions, one of which led to the global HIV–AIDS crisis. Though SIVs infect a wide range of primates, scientists have only recently begun to describe the natural history of SIV infection in their natural hosts. Several new studies reveal how both viral and host factors are responsible for the transmission to, and adaptation in, new hosts. These studies also suggest that the spread of the virus may be affected by host-specific traits, including social structure, mating system and demographic history. These studies challenge the traditional view that SIV is relatively benign in its natural host, and instead suggest that a highly dynamic relationship exists between SIV and its simian hosts. 相似文献
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The occurrence of microfloral components on medicated and non-medicated swine and chicken feed pellets and crumbles, produced in a Manitoba feed mill between June 1991 and October 1992, was determined. Addition of medicates to feeds generally decreased bacterial incidence and increased that of Eurotium spp. fungi. The effect was less pronounced when copper sulphate was added to medicated swine feeds.Contribution No. 1662. 相似文献
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Interactions of Opc-expressing Neisseria meningitidis with polarized and non-polarized human umbilical vein endothelial cells (Huvecs) were investigated. Metabolic inhibitors and cytochalasin D treatment showed that host cellular and cytoskeletal functions were important for Opc-expressing bacterial association with Huvecs at the apical surface. In addition, this interaction required the presence of serum in the incubation medium whilst association with nonpolarized cells did not require serum. Pre-exposure of Opc-expressing bacteria to serum was sufficient to increase the number of bacterial interactions at the apical surface; B306, a monoclonal antibody (mAb) against Opc, inhibited these interactions, suggesting that Ope binds to serum factor(s) and this in turn increases adherence to Huvecs. The receptors involved in this ‘sandwich’ adherence belong to the integrin family since the interaction was inhibited by peptides containing the amino acid sequence arginine-glycine-aspartic acid (RGD) and the tetrapeptide RGDS (but not the peptide RGES) was inhibitory. Non-polarized cells appeared to expose receptors/sites that bound to Opc-expressing bacteria directly, did not require serum factors and were not inhibited by RGD-containing peptides. Serum-dependent interactions of Opc-expressing bacteria to apical surface was inhibited significantly by severai mAbs against avβ3 integrins. Some mAbs against α5 and β1 caused partial inhibition; antibodies that did not block the function of β1 integrins or the mAbs against α2 integrins were not inhibitory to bacterial interactions with Huvecs. Purified vitronectin supported adherence of Opc-expressing bacteria to Huvecs but not of Opc-bacteria. These interactions were inhibited by mAb B306 against Opc, by RGDS peptides as well as by blocking antibodies directed against αvβ-3 but not antibodies against other integrins. These data suggest that a sequence of molecular events resulting in trimolecular complexes at the endothelial surface may drive neisserial invasion of Huvesc. The expression of Opc appears to enable bacteria to utilize the normal signal-transduction mechanism of host cells via ligands in sera that adhere to endothelial cell integrins. 相似文献
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J B Stanley R M Gorczynski T L Delovitch G B Mills 《Journal of immunology (Baltimore, Md. : 1950)》1989,142(10):3546-3552
Interaction of specific ligands with TCR initiates a cascade of biochemical events which leads to expression of high affinity IL-2R and subsequent IL-2 secretion. Activation of phospholipase C (PL-C) is considered to be a key event in the initiation of this cascade. However, in addition to this PL-C-dependent pathway, PL-C-independent pathways have been hypothesized. Identification of the steps constituting these PL-C-independent pathways has been difficult because activation of PL-C and the subsequent cascade of events mask the effects of such pathways. Specific inhibitors for PL-C, or mutants defective in, the PL-C pathway would facilitate delineation of alternative activation pathways. We have identified a murine pork insulin/IAd-specific T cell hybridoma, B8P3.11, in which perturbation of the B8P3.11 TCR by either Ag in association with Ia, anti-CD3 antibodies, or a mitogenic lectin does not induce increases in myo-inositol 1,4,5-triphosphate production or cytosolic free calcium, yet it does lead to IL-2 secretion. Treatment of B8P3.11 with pertussis toxin, at concentrations which ADP-ribosylate GTP-binding proteins, inhibits IL-2 secretion. Thus, signal transduction resulting in IL-2 secretion by B8P3.11 likely involves a G protein. In contrast, TCR/ligand interaction activates the PL-C-dependent pathway in LBRM 331A5, a T cell lymphoma. Furthermore, pertussis toxin treatment, which blocks IL-2 secretion by B8P3.11, does not alter IL-2 secretion by LBRM 331A5. However, similar pertussis toxin substrates are present in both cells. Therefore, B8P3.11 T cells should help to elucidate PL-C-independent activation pathways. 相似文献
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Malika Virah-Sawmy Katherine J. Willis Lindsey Gillson 《Global Ecology and Biogeography》2009,18(1):98-110
Aim Coastal biodiversity hotspots are globally threatened by sea‐level rise. As such it is important to understand how ecosystems resist, respond and adapt to sea‐level rise. Using pollen, geochemistry, charcoal and diatom records in conjunction with previously published palaeoclimatic records, we investigated the mechanism, interactions and ecosystem response and resilience of Madagascar's littoral forest to late Holocene sea‐level rise. Location Sediment sequences were collected along the south‐east coast of Madagascar in two adjacent habitats in Mandena; the highly diverse littoral forest fragment and species‐poor Erica‐matrix. Methods We used a multi‐proxy approach to investigate the relative influence of environmental changes on the littoral ecosystem. We reconstructed past vegetation and fire dynamics over the past 6500 years at two sites in the littoral forest using fossil pollen and macrofossil charcoal contained in sedimentary sequences. Alongside these records we reconstructed past marine transgressions from the same sedimentary sequences using geochemical analyses, and a salinity and drought index through the analysis of fossil diatoms. Results Our findings indicated that it was the synergistic effect of sea‐level rise coupled with rainfall deficits that triggered a threshold event with a switch from two types of littoral forest (an open Uapaca forest and a closed littoral forest fragment) to an Erica–Myrica heath/grassland occurring in approximately less than 100 years. Resilience to sea‐level rise differed in the two adjacent habitats, suggesting that the littoral forest fragment was more resilient to the impacts of sea‐level change and aridity than the open Uapaca woodland. Conclusions We demonstrated that the littoral ecosystem was influenced by late Holocene sea‐level rise and climatic desiccation. While climate change‐integrated conservation strategies address the effects of climate change on species distribution and dispersal, our work suggests that more attention should be paid to the impacts of interactive climatic variables that affect ecosystem thresholds. 相似文献
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Ruofan Wang Camille R. Simoneau Jessie Kulsuptrakul Mehdi Bouhaddou Katherine A. Travisano Jennifer M. Hayashi Jared Carlson-Stevermer James R. Zengel Christopher M. Richards Parinaz Fozouni Jennifer Oki Lauren Rodriguez Bastian Joehnk Keith Walcott Kevin Holden Anita Sil Jan E. Carette Nevan J. Krogan Andreas S. Puschnik 《Cell》2021,184(1):106-119.e14