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Search Results: 1 - 10 of 243635 matches for " Robert C. McBride "
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Robustness promotes evolvability of thermotolerance in an RNA virus
Robert C McBride, C Brandon Ogbunugafor, Paul E Turner
BMC Evolutionary Biology , 2008, DOI: 10.1186/1471-2148-8-231
Abstract: Here we demonstrate that genetic robustness increases evolvability of thermotolerance in laboratory populations of the RNA virus φ6. We observed that populations founded by robust clones evolved greater resistance to heat shock, relative to populations founded by brittle (less-robust) clones. Thus, we provide empirical evidence for the idea that robustness can promote evolvability in this environment, and further suggest that evolvability can arise indirectly via selection for robustness, rather than through direct selective action.Our data imply that greater tolerance of mutational change is associated with virus adaptability in a new niche, a finding generally relevant to evolutionary biology, and informative for elucidating how viruses might evolve to emerge in new habitats and/or overcome novel therapies.Evolvability may be defined as the capacity to adapt in response to selection [1-3], or alternatively as the ability to access evolutionary innovations [4,5]. These varied definitions echo the diverse opinions on how evolvability might be influenced by aspects of genetic architecture, especially genetic robustness – phenotypic constancy in the face of mutational change [6]. If robustness affects evolvability, it should impact the ability for organisms to access evolutionary innovations [4,5]. Robustness more easily allows for the accumulation of mutations that are neutral in the current environment; should the habitat change, this robust genetic architecture may then promote access to a relatively greater number of mutations that are beneficial for adaptation [5]. For example, a robust population may be envisioned as residing in a region of a fitness landscape that is relatively flat, owing to the high proportion of resident genotypes in the population that are equal (neutral) in fitness [7]. This creates a large 'neutral network' of genotypes that can efficiently traverse the landscape through random drift, due to their high degree of network connectivity. If e
Evolutionary genomics of host-use in bifurcating demes of RNA virus phi-6
Turner Paul E,McBride Robert C,Duffy Siobain,Montville Rebecca
BMC Evolutionary Biology , 2012, DOI: 10.1186/1471-2148-12-153
Abstract: Background Viruses are exceedingly diverse in their evolved strategies to manipulate hosts for viral replication. However, despite these differences, most virus populations will occasionally experience two commonly-encountered challenges: growth in variable host environments, and growth under fluctuating population sizes. We used the segmented RNA bacteriophage 6 as a model for studying the evolutionary genomics of virus adaptation in the face of host switches and parametrically varying population sizes. To do so, we created a bifurcating deme structure that reflected lineage splitting in natural populations, allowing us to test whether phylogenetic algorithms could accurately resolve this ‘known phylogeny’. The resulting tree yielded 32 clones at the tips and internal nodes; these strains were fully sequenced and measured for phenotypic changes in selected traits (fitness on original and novel hosts). Results We observed that RNA segment size was negatively correlated with the extent of molecular change in the imposed treatments; molecular substitutions tended to cluster on the Small and Medium RNA chromosomes of the virus, and not on the Large segment. Our study yielded a very large molecular and phenotypic dataset, fostering possible inferences on genotype-phenotype associations. Using further experimental evolution, we confirmed an inference on the unanticipated role of an allelic switch in a viral assembly protein, which governed viral performance across host environments. Conclusions Our study demonstrated that varying complexities can be simultaneously incorporated into experimental evolution, to examine the combined effects of population size, and adaptation in novel environments. The imposed bifurcating structure revealed that some methods for phylogenetic reconstruction failed to resolve the true phylogeny, owing to a paucity of molecular substitutions separating the RNA viruses that evolved in our study.
Genetic Diversity among Enterococcus faecalis
Shonna M. McBride, Vincent A. Fischetti, Donald J. LeBlanc, Robert C. Moellering, Michael S. Gilmore
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0000582
Abstract: Enterococcus faecalis, a ubiquitous member of mammalian gastrointestinal flora, is a leading cause of nosocomial infections and a growing public health concern. The enterococci responsible for these infections are often resistant to multiple antibiotics and have become notorious for their ability to acquire and disseminate antibiotic resistances. In the current study, we examined genetic relationships among 106 strains of E. faecalis isolated over the past 100 years, including strains identified for their diversity and used historically for serotyping, strains that have been adapted for laboratory use, and isolates from previously described E. faecalis infection outbreaks. This collection also includes isolates first characterized as having novel plasmids, virulence traits, antibiotic resistances, and pathogenicity island (PAI) components. We evaluated variation in factors contributing to pathogenicity, including toxin production, antibiotic resistance, polymorphism in the capsule (cps) operon, pathogenicity island (PAI) gene content, and other accessory factors. This information was correlated with multi-locus sequence typing (MLST) data, which was used to define genetic lineages. Our findings show that virulence and antibiotic resistance traits can be found within many diverse lineages of E. faecalis. However, lineages have emerged that have caused infection outbreaks globally, in which several new antibiotic resistances have entered the species, and in which virulence traits have converged. Comparing genomic hybridization profiles, using a microarray, of strains identified by MLST as spanning the diversity of the species, allowed us to identify the core E. faecalis genome as consisting of an estimated 2057 unique genes.
Characterization of Amoeboaphelidium protococcarum, an Algal Parasite New to the Cryptomycota Isolated from an Outdoor Algal Pond Used for the Production of Biofuel
Peter M. Letcher, Salvador Lopez, Robert Schmieder, Philip A. Lee, Craig Behnke, Martha J. Powell, Robert C. McBride
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0056232
Abstract: Mass culture of algae for the production of biofuels is a developing technology designed to offset the depletion of fossil fuel reserves. However, large scale culture of algae in open ponds can be challenging because of incidences of infestation with algal parasites. Without knowledge of the identity of the specific parasite and how to control these pests, algal-based biofuel production will be limited. We have characterized a eukaryotic parasite of Scenedesmus dimorphus growing in outdoor ponds used for biofuel production. We demonstrated that as the genomic DNA of parasite FD01 increases, the concentration of S. dimorphus cells decreases; consequently, this is a highly destructive pathogen. Techniques for culture of the parasite and host were developed, and the endoparasite was identified as the Aphelidea, Amoeboaphelidium protococcarum. Phylogenetic analysis of ribosomal sequences revealed that parasite FD01 placed within the recently described Cryptomycota, a poorly known phylum based on two species of Rozella and environmental samples. Transmission electron microscopy demonstrated that aplanospores of the parasite produced filose pseudopodia, which contained fine fibers the diameter of actin microfilaments. Multiple lipid globules clustered and were associated with microbodies, mitochondria and a membrane cisternae, an arrangement characteristic of the microbody-lipid globule complex of chytrid zoospores. After encystment and attachment to the host cells, the parasite injected its protoplast into the host between the host cell wall and plasma membrane. At maturity the unwalled parasite occupied the entire host cell. After cleavage of the protoplast into aplanospores, a vacuole and lipids remained in the host cell. Amoeboaphelidium protococcarum isolate FD01 is characteristic of the original description of this species and is different from strain X-5 recently characterized. Our results help put a face on the Cryptomycota, revealing that the phylum is more diverse than previously understood and include some of the Aphelidea as well as Rozella species and potentially Microsporidia.
The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis
Ruth McBride,Burtram C. Fielding
Viruses , 2012, DOI: 10.3390/v4112902
Abstract: A respiratory disease caused by a novel coronavirus, termed the severe acute respiratory syndrome coronavirus (SARS-CoV), was first reported in China in late 2002. The subsequent efficient human-to-human transmission of this virus eventually affected more than 30 countries worldwide, resulting in a mortality rate of ~10% of infected individuals. The spread of the virus was ultimately controlled by isolation of infected individuals and there has been no infections reported since April 2004. However, the natural reservoir of the virus was never identified and it is not known if this virus will re-emerge and, therefore, research on this virus continues. The SARS-CoV genome is about 30 kb in length and is predicted to contain 14 functional open reading frames (ORFs). The genome encodes for proteins that are homologous to known coronavirus proteins, such as the replicase proteins (ORFs 1a and 1b) and the four major structural proteins: nucleocapsid (N), spike (S), membrane (M) and envelope (E). SARS-CoV also encodes for eight unique proteins, called accessory proteins, with no known homologues. This review will summarize the current knowledge on SARS-CoV accessory proteins and will include: (i) expression and processing; (ii) the effects on cellular processes; and (iii) functional studies.
Pretargeted immuno-PET of CEA-expressing intraperitoneal human colonic tumor xenografts: a new sensitive detection method
Rafke Schoffelen, Winette TA van der Graaf, Robert M Sharkey, Gerben M Franssen, William J McBride, Chien-Hsing Chang, Peter Laverman, David M Goldenberg, Wim JG Oyen, Otto C Boerman
EJNMMI Research , 2012, DOI: 10.1186/2191-219x-2-5
Abstract: Two groups of female BALB/c nude mice were inoculated with LS174T human colonic tumor cells i.p. One group received 5 MBq 18F-FDG, and the other received intravenous injections of the bsmAb, followed 16 h later with 5 MBq of 68Ga-labeled peptide. One hour after the radiolabeled peptide or FDG was given, micro-PET/computed tomography images were acquired. Thereafter, the uptake of the 68Ga or 18F in dissected tissue was determined.Within 1 h, high uptake of the 68Ga-labeled peptide in the tumor lesions (23.4 ± 7.2% ID/g) and low background activity levels were observed (e.g., tumor-to-intestine ratio, 58 ± 22). This resulted in a clear visualization of all intra-abdominal tumor lesions ≥ 10 μL and even some tumors as small as 5 μL (2 mm diameter). 18F-FDG efficiently localized in the tumors (8.7 ± 3.1% ID/g) but also showed physiological uptake in various normal tissues (e.g., tumor-to-intestine ratio, 3.9 ± 1.1).Pretargeted immuno-PET with bsmAb and a 68Ga-labeled peptide could be a very sensitive imaging method for imaging colonic cancer, disclosing occult lesions.Colorectal cancer is a frequently diagnosed cancer type. It is the third most common cancer in both men and women in the Western world [1,2]. The overall 5-year survival is 40% to 60% [3,4]. The prognosis is mainly determined by the presence of local or distant metastases, especially in the liver and peritoneum, which occur in half of the patients. Only patients with a limited number of liver or lung metastases have a chance for cure by extensive surgery, generally combined with chemotherapy. However, up to half of the patients selected for metastasectomy have inoperable disease at laparotomy [5]. Therefore, preoperative staging for detecting extrahepatic disease is crucial to avoid futile major surgery [6].Specific detection of malignant colorectal tumor lesions could be achieved by (pretargeted) antibody-guided radionuclide imaging. The combination of the specificity of antibody targeting and the sensit
Modelling The Redshift-Space Three-Point Correlation Function in SDSS-III
Hong Guo,Zheng Zheng,Y. P. Jing,Idit Zehavi,Cheng Li,David H. Weinberg,Ramin A. Skibba,Robert C. Nichol,Graziano Rossi,Cristiano G. Sabiu,Donald P. Schneider,Cameron K. McBride
Physics , 2014, DOI: 10.1093/mnrasl/slv020
Abstract: We present the measurements of the redshift-space three-point correlation function (3PCF) for z~0.5 luminous red galaxies of the CMASS sample in the Sloan Digital Sky Survey-III Baryon Oscillation Spectroscopic Survey Data Release 11. The 3PCF measurements are interpreted within the halo occupation distribution framework using high-resolution N-body simulations, and the model successfully reproduces the 3PCF on scales larger than 1Mpc/h. As with the case for the redshift-space two-point correlation functions, we find that the redshift-space 3PCF measurements also favour the inclusion of galaxy velocity bias in the model. In particular, the central galaxy in a halo is on average in motion with respect to the core of the halo. We discuss the potential of the small-scale 3PCF to tighten the constraints on the relation between galaxies and dark matter haloes and on the phase-space distribution of galaxies.
Field Studies Reveal Strong Postmating Isolation between Ecologically Divergent Butterfly Populations
Carolyn S. McBride,Michael C. Singer
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1000529
Abstract: Gene flow between populations that are adapting to distinct environments may be restricted if hybrids inherit maladaptive, intermediate phenotypes. This phenomenon, called extrinsic postzygotic isolation (EPI), is thought to play a critical role in the early stages of speciation. However, despite its intuitive appeal, we know surprisingly little about the strength and prevalence of EPI in nature, and even less about the specific phenotypes that tend to cause problems for hybrids. In this study, we searched for EPI among allopatric populations of the butterfly Euphydryas editha that have specialized on alternative host plants. These populations recall a situation thought typical of the very early stages of speciation. They lack consistent host-associated genetic differentiation at random nuclear loci and show no signs of reproductive incompatibility in the laboratory. However, they do differ consistently in diverse host-related traits. For each of these traits, we first asked whether hybrids between populations that use different hosts (different-host hybrids) were intermediate to parental populations and to hybrids between populations that use the same host (same-host hybrids). We then conducted field experiments to estimate the effects of intermediacy on fitness in nature. Our results revealed strong EPI under field conditions. Different-host hybrids exhibited an array of intermediate traits that were significantly maladaptive, including four behaviors. Intermediate foraging height slowed the growth of larvae, while intermediate oviposition preference, oviposition site height, and clutch size severely reduced the growth and survival of the offspring of adult females. We used our empirical data to construct a fitness surface on which different-host hybrids can be seen to fall in an adaptive valley between two peaks occupied by same-host hybrids. These findings demonstrate how ecological selection against hybrids can create a strong barrier to gene flow at the early stages of adaptive divergence.
Field Studies Reveal Strong Postmating Isolation between Ecologically Divergent Butterfly Populations
Carolyn S. McBride ,Michael C. Singer
PLOS Biology , 2010, DOI: 10.1371/journal.pbio.1000529
Abstract: Gene flow between populations that are adapting to distinct environments may be restricted if hybrids inherit maladaptive, intermediate phenotypes. This phenomenon, called extrinsic postzygotic isolation (EPI), is thought to play a critical role in the early stages of speciation. However, despite its intuitive appeal, we know surprisingly little about the strength and prevalence of EPI in nature, and even less about the specific phenotypes that tend to cause problems for hybrids. In this study, we searched for EPI among allopatric populations of the butterfly Euphydryas editha that have specialized on alternative host plants. These populations recall a situation thought typical of the very early stages of speciation. They lack consistent host-associated genetic differentiation at random nuclear loci and show no signs of reproductive incompatibility in the laboratory. However, they do differ consistently in diverse host-related traits. For each of these traits, we first asked whether hybrids between populations that use different hosts (different-host hybrids) were intermediate to parental populations and to hybrids between populations that use the same host (same-host hybrids). We then conducted field experiments to estimate the effects of intermediacy on fitness in nature. Our results revealed strong EPI under field conditions. Different-host hybrids exhibited an array of intermediate traits that were significantly maladaptive, including four behaviors. Intermediate foraging height slowed the growth of larvae, while intermediate oviposition preference, oviposition site height, and clutch size severely reduced the growth and survival of the offspring of adult females. We used our empirical data to construct a fitness surface on which different-host hybrids can be seen to fall in an adaptive valley between two peaks occupied by same-host hybrids. These findings demonstrate how ecological selection against hybrids can create a strong barrier to gene flow at the early stages of adaptive divergence.
Broadly Neutralizing Antibody PGT121 Allosterically Modulates CD4 Binding via Recognition of the HIV-1 gp120 V3 Base and Multiple Surrounding Glycans
Jean-Philippe Julien,Devin Sok,Reza Khayat,Jeong Hyun Lee,Katie J. Doores,Laura M. Walker,Alejandra Ramos,Devan C. Diwanji,Robert Pejchal,Albert Cupo,Umesh Katpally,Rafael S. Depetris,Robyn L. Stanfield,Ryan McBride,Andre J. Marozsan,James C. Paulson,Rogier W. Sanders,John P. Moore,Dennis R. Burton,Pascal Poignard,Andrew B. Ward ,Ian A. Wilson
PLOS Pathogens , 2013, DOI: 10.1371/journal.ppat.1003342
Abstract: New broad and potent neutralizing HIV-1 antibodies have recently been described that are largely dependent on the gp120 N332 glycan for Env recognition. Members of the PGT121 family of antibodies, isolated from an African donor, neutralize ~70% of circulating isolates with a median IC50 less than 0.05 μg ml?1. Here, we show that three family members, PGT121, PGT122 and PGT123, have very similar crystal structures. A long 24-residue HCDR3 divides the antibody binding site into two functional surfaces, consisting of an open face, formed by the heavy chain CDRs, and an elongated face, formed by LCDR1, LCDR3 and the tip of the HCDR3. Alanine scanning mutagenesis of the antibody paratope reveals a crucial role in neutralization for residues on the elongated face, whereas the open face, which accommodates a complex biantennary glycan in the PGT121 structure, appears to play a more secondary role. Negative-stain EM reconstructions of an engineered recombinant Env gp140 trimer (SOSIP.664) reveal that PGT122 interacts with the gp120 outer domain at a more vertical angle with respect to the top surface of the spike than the previously characterized antibody PGT128, which is also dependent on the N332 glycan. We then used ITC and FACS to demonstrate that the PGT121 antibodies inhibit CD4 binding to gp120 despite the epitope being distal from the CD4 binding site. Together, these structural, functional and biophysical results suggest that the PGT121 antibodies may interfere with Env receptor engagement by an allosteric mechanism in which key structural elements, such as the V3 base, the N332 oligomannose glycan and surrounding glycans, including a putative V1/V2 complex biantennary glycan, are conformationally constrained.
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