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101.
Victoria K. Korboukh Cheri A. Lee Ashley Acevedo Marco Vignuzzi Yinghong Xiao Jamie J. Arnold Stephen Hemperly Jason D. Graci Avery August Raul Andino Craig E. Cameron 《The Journal of biological chemistry》2014,289(43):29531-29544
The ability of an RNA virus to exist as a population of genetically distinct variants permits the virus to overcome events during infections that would otherwise limit virus multiplication or drive the population to extinction. Viral genetic diversity is created by the ribonucleotide misincorporation frequency of the viral RNA-dependent RNA polymerase (RdRp). We have identified a poliovirus (PV) RdRp derivative (H273R) possessing a mutator phenotype. GMP misincorporation efficiency for H273R RdRp in vitro was increased by 2–3-fold that manifested in a 2–3-fold increase in the diversity of the H273R PV population in cells. Circular sequencing analysis indicated that some mutations were RdRp-independent. Consistent with the population genetics theory, H273R PV was driven to extinction more easily than WT in cell culture. Furthermore, we observed a substantial reduction in H273R PV virulence, measured as the ability to cause paralysis in the cPVR mouse model. Reduced virulence correlated with the inability of H273R PV to sustain replication in tissues/organs in which WT persists. Despite the attenuated phenotype, H273R PV was capable of replicating in mice to levels sufficient to induce a protective immune response, even when the infecting dose used was insufficient to elicit any visual signs of infection. We conclude that optimal RdRp fidelity is a virulence determinant that can be targeted for viral attenuation or antiviral therapies, and we suggest that the RdRp may not be the only source of mutations in a RNA virus genome. 相似文献
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103.
Nechamen CA Thomas RM Cohen BD Acevedo G Poulikakos PI Testa JR Dias JA 《Biology of reproduction》2004,71(2):629-636
Selection of a dominant follicle that will ovulate likely occurs by activation of cell survival pathways and suppression of death-promoting pathways in a mechanism involving FSH and its cognate receptor (FSHR). A yeast two-hybrid screen of an ovarian cDNA library was employed to identify potential interacting partners with human FSHR intracellular loops 1 and 2. Among eight cDNA clones identified in the screen, APPL1 (adaptor protein containing PH domain, PTB domain, and leucine zipper motif; also known as APPL or DIP13alpha) was chosen for further analysis. APPL1 appears to coimmunoprecipitate with FSHR in HEK 293 cells stably expressing FSHR (293/FSHR cells), confirming APPL1 as a potential FSHR-interacting partner. The phosphorylation status of members of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway was also examined because of the proposed role of APPL1 in the antiapoptotic PI3K/Akt pathway. FOXO1a, also referred to as forkhead homologue in rhabdomyosarcoma, is a downstream effector in the pathway and tightly linked to expression of proapoptotic genes. FOXO1a, but not the upstream kinase Akt, is rapidly phosphorylated, and FOXO1a is thereby inactivated when 293/FSHR cells are treated with FSH. In addition, FSHR coimmunoprecipitates with Akt. The identification of APPL1 as a potential interactor with FSHR and the finding that FOXO1a is phosphorylated in response to FSH provide a possible link between FSH and PI3K/Akt signaling, which may help to delineate a survival mechanism whereby FSH selects the dominant follicle to survive. 相似文献
104.
Silvana Acevedo Stephen Saddlier Pam Clunie Renae Ayres 《Ecological Management & Restoration》2013,14(2):112-119
There are no national emergency response arrangements for freshwater pest fish incursions in Australia. Individual States and Territories vary widely in their current response arrangements to freshwater pest fish incursions, with many being dealt with on an ad‐hoc basis and with varying degrees of efficacy. In recognition of this, the Invasive Animals Cooperative Research Centre funded a project to ‘Advance the development of national emergency response arrangements for freshwater fish incursions in Australia’. One of the recommendations of this project was creating a web‐based support tool (DST) to provide direction and assistance in managing freshwater pest fish incursions. This article describes the DST created. The DST leads the user through a series of questions relating to the species sighting, details of the fish and its capture, and site information at a particular location. These questions address issues that managers must consider when choosing appropriate control techniques. Information entered in two sections (site details and fish details) influence the suggested control techniques. The final product of the DST is a standard online report that contains a summary of all information entered and a ranking of the most common control techniques used in Australia. The report is then submitted to and assessed by the relevant State Government authority responsible for the management of freshwater pest fish incursions. Managers are then able to consider their options, taking into consideration current permits, resources and capability. The DST is anticipated to maximize the speed and quality of freshwater pest fish incursion reporting and to help the responsible government agency decide on the most appropriate management action. The DST will also provide government agency staff access to other relevant information and facilitate consistency in the decision‐making approach by government agencies throughout Australia. 相似文献
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106.
Jessica L. Deichmann Orlando Acevedo‐Charry Leah Barclay Zuzana Burivalova Marconi Campos‐Cerqueira Fernando d'Horta Edward T. Game Benjamin L. Gottesman Patrick J. Hart Ammie K. Kalan Simon Linke Leandro Do Nascimento Bryan Pijanowski Erica Staaterman T. Mitchell Aide 《Biotropica》2018,50(5):713-718
Knowledge that can be gained from acoustic data collection in tropical ecosystems is low‐hanging fruit. There is every reason to record and with every day, there are fewer excuses not to do it. In recent years, the cost of acoustic recorders has decreased substantially (some can be purchased for under US$50, e.g., Hill et al. 2018) and the technology needed to store and analyze acoustic data is continuously improving (e.g., Corrada Bravo et al. 2017, Xie et al. 2017). Soundscape recordings provide a permanent record of a site at a given time and contain a wealth of invaluable and irreplaceable information. Although challenges remain, failure to collect acoustic data now in tropical ecosystems would represent a failure to future generations of tropical researchers and the citizens that benefit from ecological research. In this commentary, we (1) argue for the need to increase acoustic monitoring in tropical systems; (2) describe the types of research questions and conservation issues that can be addressed with passive acoustic monitoring (PAM) using both short‐ and long‐term data in terrestrial and freshwater habitats; and (3) present an initial plan for establishing a global repository of tropical recordings. 相似文献
107.
Hasan Alniss Bita Zamiri Melisa Khalaj Christopher E. Pearson Robert B. Macgregor 《Biochemical and biophysical research communications》2018,495(4):2410-2417
Background
An expansion of the hexanucleotide repeat (GGGGCC)n·(GGCCCC)n in the C9orf72 promoter has been shown to be the cause of Amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). The C9orf72 repeat can form four-stranded structures; the cationic porphyrin (TMPyP4) binds and distorts these structures.Methods
Isothermal titration calorimetry (ITC), and circular dichroism (CD) were used to study the binding of TMPyP4 to the C-rich and G-rich DNA and RNA oligos containing the hexanucleotide repeat at pH 7.5 and 0.1?M?K+.Results
The CD spectra of G-rich DNA and RNA TMPyP4 complexes showed features of antiparallel and parallel G-quadruplexes, respectively. The shoulder at 260?nm in the CD spectrum becomes more intense upon formation of complexes between TMPyP4 and the C-rich DNA. The peak at 290?nm becomes more intense in the c-rich RNA molecules, suggesting induction of an i-motif structure. The ITC data showed that TMPyP4 binds at two independent sites for all DNA and RNA molecules.Conclusions
For DNA, the data are consistent with TMPyP4 stacking on the terminal tetrads and intercalation. For RNA, the thermodynamics of the two binding modes are consistent with groove binding and intercalation. In both cases, intercalation is the weaker binding mode. These findings are considered with respect to the structural differences of the folded DNA and RNA molecules and the energetics of the processes that drive site-specific recognition by TMPyP4; these data will be helpful in efforts to optimize the specificity and affinity of the binding of porphyrin-like molecules. 相似文献108.
The metabolism of chloroguaiacols by a soil bacterium was studied. The strain was isolated by enrichment with guaiacol as the sole carbon and energy source, and identified as a Rhodococcus ruber CA16. None of seven chlorinated, guaiacols supported bacterial growth. However, ultraviolet spectroscopy chloride release, and oxygen consumption showed that resting cells grown on guaiacol degraded completely 4-chloroguaiacol 5-chloroguaiacol and 6-chloroguaiacol and, to a lesser extent, 4,5-dichloroguaiacol Gas chromatographic analysis suggested microbial formation of 4-chlorocatechol and 4,5-dichlorocatechol from 4-chloroguaiacol and 4,5-dichloroguaiacol, respectively. Although mono-and dichloroguaiacols did not affect the strain's ability to grow on guaiacol, chlorocatechols completely arrested growth. The role of chlorocatechols in chloroguaiacol metabolism by this guaiacol-degrading bacterial strain is discussed. 相似文献
109.
The genes that encode the gonococcal transferrin binding proteins,TbpB and TbpA,are differentially regulated by MisR under iron‐replete and iron‐depleted conditions
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Justin L. Kandler Rosuany Vélez Acevedo Mary Kathryne Dickinson Devin R. Cash William M. Shafer Cynthia Nau Cornelissen 《Molecular microbiology》2016,102(1):137-151
Neisseria gonorrhoeae produces two transferrin binding proteins, TbpA and TbpB, which together enable efficient iron transport from human transferrin. We demonstrate that expression of the tbp genes is controlled by MisR, a response regulator in the two‐component regulatory system that also includes the sensor kinase MisS. The tbp genes were up‐regulated in the misR mutant under iron‐replete conditions but were conversely down‐regulated in the misR mutant under iron‐depleted conditions. The misR mutant was capable of transferrin‐iron uptake at only 50% of wild‐type levels, consistent with decreased tbp expression. We demonstrate that phosphorylated MisR specifically binds to the tbpBA promoter and that MisR interacts with five regions upstream of the tbpB start codon. These analyses confirm that MisR directly regulates tbpBA expression. The MisR binding sites in the gonococcus are only partially conserved in Neisseria meningitidis, which may explain why tbpBA was not MisR‐regulated in previous studies using this related pathogen. This is the first report of a trans‐acting protein factor other than Fur that can directly contribute to gonococcal tbpBA regulation. 相似文献