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51.
Allicock OM Lemey P Tatem AJ Pybus OG Bennett SN Mueller BA Suchard MA Foster JE Rambaut A Carrington CV 《Molecular biology and evolution》2012,29(6):1533-1543
Changes in Dengue virus (DENV) disease patterns in the Americas over recent decades have been attributed, at least in part, to repeated introduction of DENV strains from other regions, resulting in a shift from hypoendemicity to hyperendemicity. Using newly sequenced DENV-1 and DENV-3 envelope (E) gene isolates from 11 Caribbean countries, along with sequences available on GenBank, we sought to document the population genetic and spatiotemporal transmission histories of the four main invading DENV genotypes within the Americas and investigate factors that influence the rate and intensity of DENV transmission. For all genotypes, there was an initial invasion phase characterized by rapid increases in genetic diversity, which coincided with the first confirmed cases of each genotype in the region. Rapid geographic dispersal occurred upon each genotype's introduction, after which individual lineages were locally maintained, and gene flow was primarily observed among neighboring and nearby countries. There were, however, centers of viral diversity (Barbados, Puerto Rico, Colombia, Suriname, Venezuela, and Brazil) that were repeatedly involved in gene flow with more distant locations. For DENV-1 and DENV-2, we found that a "distance-informed" model, which posits that the intensity of virus movement between locations is inversely proportional to the distance between them, provided a better fit than a model assuming equal rates of movement between all pairs of countries. However, for DENV-3 and DENV-4, the more stochastic "equal rates" model was preferred. 相似文献
52.
Attilio Fabbretti Letizia Brandi Dezemona Petrelli Cynthia L. Pon Nilo R. Casta?edo Ricardo Medina Claudio O. Gualerzi 《Nucleic acids research》2012,40(20):10366-10374
Furvina®, also denominated G1 (MW 297), is a synthetic nitrovinylfuran [2-bromo-5-(2-bromo-2-nitrovinyl)-furan] antibiotic with a broad antimicrobial spectrum. An ointment (Dermofural®) containing G1 as the only active principle is currently marketed in Cuba and successfully used to treat dermatological infections. Here we describe the molecular target and mechanism of action of G1 in bacteria and demonstrate that in vivo G1 preferentially inhibits protein synthesis over RNA, DNA and cell wall synthesis. Furthermore, we demonstrate that G1 targets the small ribosomal subunit, binds at or near the P-decoding site and inhibits its function interfering with the ribosomal binding of fMet-tRNA during 30S initiation complex (IC) formation ultimately inhibiting translation. Notably, this G1 inhibition displays a bias for the nature (purine vs. pyrimidine) of the 3′-base of the codon, occurring efficiently only when the mRNA directing 30S IC formation and translation contains the canonical AUG initiation triplet or the rarely found AUA triplet, but hardly occurs when the mRNA start codon is either one of the non-canonical triplets AUU or AUC. This codon discrimination by G1 is reminiscent, though of opposite type of that displayed by IF3 in its fidelity function, and remarkably does not occur in the absence of this factor. 相似文献
53.
54.
Thompson AL Johnson BT Sempowski GD Gunn MD Hou B DeFranco AL Staats HF 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(6):2834-2846
IL-1 has been shown to have strong mucosal adjuvant activities, but little is known about its mechanism of action. We vaccinated IL-1R1 bone marrow (BM) chimeric mice to determine whether IL-1R1 expression on stromal cells or hematopoietic cells was sufficient for the maximal adjuvant activity of nasally delivered IL-1α as determined by the acute induction of cytokine responses and induction of Bacillus anthracis lethal factor (LF)-specific adaptive immunity. Cytokine and chemokine responses induced by vaccination with IL-1α were predominantly derived from the stromal cell compartment and included G-CSF, IL-6, IL-13, MCP-1, and keratinocyte chemoattractant. Nasal vaccination of Il1r1(-/-) (knock-out [KO]) mice given wild-type (WT) BM (WT→KO) and WT→WT mice with LF + IL-1α induced maximal adaptive immune responses, whereas vaccination of WT mice given Il1r1(-/-) BM (KO→WT) resulted in significantly decreased production of LF-specific serum IgG, IgG subclasses, lethal toxin-neutralizing Abs, and mucosal IgA compared with WT→KO and WT→WT mice (p < 0.05). IL-1α adjuvant activity was not dependent on mast cells. However, the ability of IL-1α to induce serum LF-specific IgG2c and lethal toxin-neutralizing Abs was significantly impaired in CD11c-Myd88(-/-) mice when compared with WT mice (p < 0.05). Our results suggest that CD11c(+) cells must be directly activated by nasally administered IL-1α for maximal adjuvant activity and that, although stromal cells are required for maximal adjuvant-induced cytokine production, the adjuvant-induced stromal cell cytokine responses are not required for effective induction of adaptive immunity. 相似文献
55.
Hochwender CG Cha DH Czesak ME Fritz RS Smyth RR Kaufman AD Warren B Neuman A 《Oecologia》2012,169(1):49-60
To determine the mechanistic basis of tolerance, we evaluated six candidate traits for tolerance to damage using F2 interspecific hybrids in a willow hybrid system. A distinction was made between reproductive tolerance and biomass tolerance;
reproductive tolerance was designated as a plant’s proportional change in catkin production following damage, while biomass
tolerance referred to a plant’s proportional change in biomass (i.e., regrowth) following damage. F2 hybrids were generated to increase variation and independence among candidate traits. Using three clonally identical individuals,
pre-damage candidate traits for tolerance to damage (root:shoot ratio, total nonstructural carbohydrate, and total available
protein) and post-damage candidate traits (relative root:shoot ratio, phenolic ratio, and specific leaf area ratio) were measured.
The range of variation for these six candidate traits was broad. Biomass was significantly increased two years after 50% shoot
length removal, and catkin production was not significantly reduced when damaged, suggesting that F2 hybrids had great biomass tolerance and reproductive tolerance. Based on multiple regression methods, increased reproductive
tolerance was associated with increased protein storage and decreased relative root:shoot ratio (reduced root allocation after
damage). In addition, a positive relationship between biomass tolerance and condensed tannins was detected, and both traits
were associated with increased reproductive tolerance. These four factors explained 57% of the variance in the reproductive
tolerance of F2 hybrids, but biomass tolerance explained the majority of the variance in reproductive tolerance. Changes in plant architecture
in response to plant damage may be the underlying mechanism that explains biomass tolerance. 相似文献
56.
Ceci M Welshhans K Ciotti MT Brandi R Parisi C Paoletti F Pistillo L Bassell GJ Cattaneo A 《PloS one》2012,7(4):e35034
In neurons, specific mRNAs are transported in a translationally repressed manner along dendrites or axons by transport ribonucleic-protein complexes called RNA granules. ZBP1 is one RNA binding protein present in transport RNPs, where it transports and represses the translation of cotransported mRNAs, including β-actin mRNA. The release of β-actin mRNA from ZBP1 and its subsequent translation depends on the phosphorylation of ZBP1 by Src kinase, but little is known about how this process is regulated. Here we demonstrate that the ribosomal-associated protein RACK1, another substrate of Src, binds the β-actin mRNA/ZBP1 complex on ribosomes and contributes to the release of β-actin mRNA from ZBP1 and to its translation. We identify the Src binding and phosphorylation site Y246 on RACK1 as the critical site for the binding to the β-actin mRNA/ZBP1 complex. Based on these results we propose RACK1 as a ribosomal scaffold protein for specific mRNA-RBP complexes to tightly regulate the translation of specific mRNAs. 相似文献
57.
Tom G. Schwan Jennifer M. Anderson Job E. Lopez Robert J. Fischer Sandra J. Raffel Brandi N. McCoy David Safronetz Nafomon Sogoba Ousmane Ma?ga Sékou F. Traoré 《PLoS neglected tropical diseases》2012,6(11)
Background
Tick-borne relapsing fever spirochetes are maintained in endemic foci that involve a diversity of small mammals and argasid ticks in the genus Ornithodoros. Most epidemiological studies of tick-borne relapsing fever in West Africa caused by Borrelia crocidurae have been conducted in Senegal. The risk for humans to acquire relapsing fever in Mali is uncertain, as only a few human cases have been identified. Given the high incidence of malaria in Mali, and the potential to confuse the clinical diagnosis of these two diseases, we initiated studies to determine if there were endemic foci of relapsing fever spirochetes that could pose a risk for human infection.Methodology/Principal Findings
We investigated 20 villages across southern Mali for the presence of relapsing fever spirochetes. Small mammals were captured, thin blood smears were examined microscopically for spirochetes, and serum samples were tested for antibodies to relapsing fever spirochetes. Ornithodoros sonrai ticks were collected and examined for spirochetal infection. In total, 11.0% of the 663 rodents and 14.3% of the 63 shrews tested were seropositive and 2.2% of the animals had active spirochete infections when captured. In the Bandiagara region, the prevalence of infection was higher with 35% of the animals seropositive and 10% infected. Here also Ornithodoros sonrai were abundant and 17.3% of 278 individual ticks tested were infected with Borrelia crocidurae. Fifteen isolates of B. crocidurae were established and characterized by multi-locus sequence typing.Conclusions/Significance
The potential for human tick-borne relapsing fever exists in many areas of southern Mali. 相似文献58.
59.
Miguel A. Lanaspa Laura G. Sanchez-Lozada Christina Cicerchi Nanxing Li Carlos A. Roncal-Jimenez Takuji Ishimoto Myphuong Le Gabriela E. Garcia Jeffrey B. Thomas Christopher J. Rivard Ana Andres-Hernando Brandi Hunter George Schreiner Bernardo Rodriguez-Iturbe Yuri Y. Sautin Richard J. Johnson 《PloS one》2012,7(10)
60.
ML Zupancic BL Cantarel Z Liu EF Drabek KA Ryan S Cirimotich C Jones R Knight WA Walters D Knights EF Mongodin RB Horenstein BD Mitchell N Steinle S Snitker AR Shuldiner CM Fraser 《PloS one》2012,7(8):e43052
Obesity has been linked to the human gut microbiota; however, the contribution of gut bacterial species to the obese phenotype remains controversial because of conflicting results from studies in different populations. To explore the possible dysbiosis of gut microbiota in obesity and its metabolic complications, we studied men and women over a range of body mass indices from the Old Order Amish sect, a culturally homogeneous Caucasian population of Central European ancestry. We characterized the gut microbiota in 310 subjects by deep pyrosequencing of bar-coded PCR amplicons from the V1-V3 region of the 16S rRNA gene. Three communities of interacting bacteria were identified in the gut microbiota, analogous to previously identified gut enterotypes. Neither BMI nor any metabolic syndrome trait was associated with a particular gut community. Network analysis identified twenty-two bacterial species and four OTUs that were either positively or inversely correlated with metabolic syndrome traits, suggesting that certain members of the gut microbiota may play a role in these metabolic derangements. 相似文献