Repeated spillovers of the H1N1 pandemic virus (H1N1pdm09) from humans to pigs resulted in substantial evolution of influenza A viruses infecting swine, contributing to the genetic and antigenic diversity of influenza A viruses (IAV) currently circulating in swine. The reassortment with endemic swine viruses and maintenance of some of the H1N1pdm09 internal genes resulted in the circulation of different genomic constellations in pigs. Here, we performed a whole-genome phylogenetic analysis of 368 IAV circulating in swine from 2009 to 2016 in the United States. We identified 44 different genotypes, with the most common genotype (32.33%) containing a clade IV-A HA gene, a 2002-lineage NA gene, an M-pdm09 gene, and remaining gene segments of triple reassortant internal gene (TRIG) origin. To understand how different genetic constellations may relate to viral fitness, we compared the pathogenesis and transmission in pigs of six representative genotypes. Although all six genotypes efficiently infected pigs, they resulted in different degrees of pathology and viral shedding. These results highlight the vast H3N2 genetic diversity circulating in U.S. swine after 2009. This diversity has important implications in the control of this disease by the swine industry, as well as a potential risk for public health if swine-adapted viruses with H1N1pdm09 genes have an increased risk to humans, as occurred in the 2011-2012 and 2016 human variant H3N2v cases associated with exhibition swine.
IMPORTANCE People continue to spread the 2009 H1N1 pandemic (H1N1pdm09) IAV to pigs, allowing H1N1pdm09 to reassort with endemic swine IAV. In this study, we determined the 8 gene combinations of swine H3N2 IAV detected from 2009 to 2016. We identified 44 different genotypes of H3N2, the majority of which contained at least one H1N1pdm09 gene segment. We compared six representative genotypes of H3N2 in pigs. All six genotypes efficiently infected pigs, but they resulted in different degrees of lung damage and viral shedding. These results highlight the vast genetic diversity of H3N2 circulating in U.S. swine after 2009, with important implications for the control of IAV for the swine industry. Because H1N1pdm09 is also highly adapted to humans, these swine viruses pose a potential risk to public health if swine-adapted viruses with H1N1pdm09 genes also have an increased risk for human infection.
Many interesting combinatorial problems can be optimized efficiently using recursive computations often termed discrete dynamic programming. In this paper, we develop a paradigm for a general class of such optimizations that yields a polyhedral description for each model in the class. The elementary concept of dynamic programs as shortest path problems in acyclic graphs is generalized to one seeking a least cost solution in a directed hypergraph. Sufficient conditions are then provided for binary integrality of the associated hyperflow problem. Given a polynomially solvable dynamic program, the result is a linear program, in polynomially many variables and constraints, having the solution vectors of the dynamic program as its extreme-point optima. That is, the linear program provides a succinct characterization of the solutions to the underlying optimization problem expressed through an appropriate change of variables. We also discuss projecting this formulation to recover constraints on the original variables and illustrate how some important dynamic programming solvable models fit easily into our paradigm. A classic multiechelon lot sizing problem in production and a host of optimization problems on recursively defined classes of graphs are included.
Mycobacterium peregrinum consists of two taxa: types I and II. We evaluated 43 clinical type II strains from throughout the United States. They were responsible for soft-tissue and bone infections, catheter-related infections, and possible pneumonitis. By carbohydrate utilization, they were indistinguishable from type I strains, being D-mannitol and trehalose positive. However, they had a distinct susceptibility pattern that included intermediate ciprofloxacin MICs but low clarithromycin and doxycycline MICs of <1 g/ml. These features were also shared by reference isolates of Mycobacterium senegalense from African bovine cases of "farcy." By 16S rRNA gene sequencing, the type II isolates shared 100% sequence identity with M. senegalense. Partial sequencing of the type II hsp65 gene (441 bp) revealed four sequevars showing >98.4% identity with each other and >98.6% identity with the sequence of five bovine strains of M. senegalense. There was <97.1% identity with M. peregrinum type I isolates and other Mycobacterium fortuitum group species. Sequencing of additional gene targets including the 16S-23S rDNA internal transcribed spacer region and the rpoB gene (partial sequence) revealed a similar phylogenetic grouping. DNA-DNA hybridization showed 76 to 99% relatedness between the bovine and human strains. These studies demonstrate that type II isolates are not isolates of M. peregrinum but represent human strains of M. senegalense. This study is the first to demonstrate this species as a human pathogen. Representative human M. senegalense strains include ATCC 35755 and newly submitted strains ATCC BAA-849, ATCC BAA-850, and ATCC BAA-851.
Changing conditions along plate boundaries are thought to result in the reactivation of preexisting structures. The offshore southern California Borderland has undergone dramatic adjustments as conditions changed from subduction tectonics to transform tectonics, including major Miocene oblique extension, followed by transpressional fault reactivation. However, consensus is still lacking about stratigraphic age models, fault geometry, and slip history for the near-offshore area between southern Los Angeles and San Diego (California, USA). We interpret an extensive data set of seismic reflection, bathymetric, and stratigraphic data from that area to determine the three-dimensional geometry and kinematic evolution of the faults and folds and document how preexisting structures have changed their activity and type of slip through time. The resulting structural representation reveals a moderately landward-dipping San Mateo-Carlsbad fault that converges downward with the steeper, right-lateral Newport-Inglewood fault, forming a fault wedge affected by Quaternary contractional folding. This fault wedge deformed in transtension during late Miocene through Pliocene time. Subsequently, the San Mateo-Carlsbad fault underwent 0.6-1.0 km displacement, spatially varying between reverse right lateral and transtensional right lateral. In contrast, shallow parts of the previously identified gently dipping Oceanside detachment and the faults above it appear to have been inactive since the early Pliocene. These observations, together with new and revised geometric representations of additional steeper faults, and the evidence for a pervasive strike-slip component on these nearshore faults, suggest a need to revise the earthquake hazard estimates for the coastal region.
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