Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

Discontinuous Galerkin approximations in computational mechanics: hybridization, exact geometry and degree adaptivity

Discontinuous Galerkin (DG) discretizations with exact representation of the geometry and local polynomial degree adaptivity are revisited. Hybridization techniques are employed to reduce the computational cost of DG approximations and devise the hybridizable discontinuous Galerkin (HDG) method. Exact geometry described by non-uniform rational B-splines (NURBS) is integrated into HDG using the framework of the NURBS-enhanced finite element method (NEFEM). Moreover, optimal convergence and superconvergence properties of HDG-Voigt formulation in presence of symmetric second-order tensors are exploited to construct inexpensive error indicators and drive degree adaptive procedures. Applications involving the numerical simulation of problems in electrostatics, linear elasticity and incompressible viscous flows are presented. Moreover, this is done for both high-order HDG approximations and the lowest-order framework of face-centered finite volumes (FCFV).Peer ReviewedPostprint (author's final draft

The complex hybrid origins of the root knot nematodes revealed through comparative genomics

Meloidogyne root knot nematodes (RKN) can infect most of the world's agricultural crop species and are among the most important of all plant pathogens. As yet however we have little understanding of their origins or the genomic basis of their extreme polyphagy. The most damaging pathogens reproduce by mitotic parthenogenesis and are suggested to originate by interspecific hybridizations between unknown parental taxa. We sequenced the genome of the diploid meiotic parthenogen Meloidogyne floridensis, and use a comparative genomic approach to test the hypothesis that it was involved in the hybrid origin of the tropical mitotic parthenogen M. incognita. Phylogenomic analysis of gene families from M. floridensis, M. incognita and an outgroup species M. hapla was used to trace the evolutionary history of these species' genomes, demonstrating that M. floridensis was one of the parental species in the hybrid origins of M. incognita. Analysis of the M. floridensis genome revealed many gene loci present in divergent copies, as they are in M. incognita, indicating that it too had a hybrid origin. The triploid M. incognita is shown to be a complex double-hybrid between M. floridensis and a third, unidentified parent. The agriculturally important RKN have very complex origins involving the mixing of several parental genomes by hybridization and their extreme polyphagy and agricultural success may be related to this hybridization, producing transgressive variation on which natural selection acts. Studying RKN variation via individual marker loci may fail due to the species' convoluted origins, and multi-species population genomics is essential to understand the hybrid diversity and adaptive variation of this important species complex. This comparative genomic analysis provides a compelling example of the importance and complexity of hybridization in generating animal species diversity more generally

Rapid evolution of morphology and adaptive life history in the invasive California wild radish (Raphanus sativus) and the implications for management.

Understanding the evolution and demography of invasive populations may be key for successful management. In this study, we test whether or not populations of the non-native, hybrid-derived California wild radish have regionally adapted to divergent climates over their 150-year history in California and determine if population demographic dynamics might warrant different region-specific strategies for control. Using a reciprocal transplant approach, we found evidence for genetically based differences both between and among northern, coastal and southern, inland populations of wild radish. Individual fitness was analyzed using a relatively new statistical method called 'aster modeling' which integrates temporally sequential fitness measurements. In their respective home environments, fitness differences strongly favored southern populations and only slightly favored northern populations. Demographic rates of transition and sensitivities also differed between regions of origin, suggesting that the most effective approach for reducing overall population growth rate would be to target different life-history stages in each region

A MOS-based Dynamic Memetic Differential Evolution Algorithm for Continuous Optimization: A Scalability Test

Continuous optimization is one of the areas with more activity in the field of heuristic optimization. Many algorithms have been proposed and compared on several benchmarks of functions, with different performance depending on the problems. For this reason, the combination of different search strategies seems desirable to obtain the best performance of each of these approaches. This contribution explores the use of a hybrid memetic algorithm based on the multiple offspring framework. The proposed algorithm combines the explorative/exploitative strength of two heuristic search methods that separately obtain very competitive results. This algorithm has been tested with the benchmark problems and conditions defined for the special issue of the Soft Computing Journal on Scalability of Evolutionary Algorithms and other Metaheuristics for Large Scale Continuous Optimization Problems. The proposed algorithm obtained the best results compared with both its composing algorithms and a set of reference algorithms that were proposed for the special issue

Analysis of the role of the p47 GTPase IIGP1 in Resistance against Intracellular Pathogens

IIGP1 is a member of the p47 GTPase family of IFNγ-induced proteins, which are among the most potent presently known mediators of cell-autonomous resistance against intracellular bacterial and protozoan pathogens in the mouse. From all studied members of this family IIGP1 is the best characterized with respect to biochemical characteristics and enzymatic activity in vitro, as well as membrane binding properties and dynamic behavior in cells. The role of the protein in intracellular defense was however, unknown and this study was set as an initial attempt to reveal it. This thesis describes the generation of an IIGP1 deficient mouse and analysis of the susceptibility of this animal to pathogens from protozoan and bacterial origin, which employ diverse strategies for host cell invasion and intracellular survival and replication. Despite having intact adaptive immune system, the IIGP1 deficient mice showed higher incidence of development of cerebral malaria after infection with Plasmodium berghei sporozoites. In addition, IIGP1 deficient astrocytes exhibited a partial loss of IFNγ-induced inhibition of Toxoplasma gondii growth. IIGP1 deficient animals were not susceptible to infection with Leishmania major, Listeria monocytogenes, Chlamydia trachomatis and Anaplasma phagocytophilum. From the analysis of the obtained data in the context of the intracellular lifestyle of the pathogens involved in this study, we concluded that IIGP1 seems to be specifically involved in defense against protozoan parasites, which like Pl. berghei and T. gondii reside in non-fusigenic parasitophorous vacuoles after entering cells. The mechanisms of IIGP1-dependent protection of cells against these pathogens remain to be studied

Group testing problems in experimental molecular biology

In group testing, the task is to determine the distinguished members of a set of objects L by asking subset queries of the form ``does the subset Q of L contain a distinguished object?'' The primary biological application of group testing is for screening libraries of clones with hybridization probes. This is a crucial step in constructing physical maps and for finding genes. Group testing has also been considered for sequencing by hybridization. Another important application includes screening libraries of reagents for useful chemically active zones. This preliminary report discusses some of the constrained group testing problems which arise in biology.Comment: 7 page

Review of precision cancer medicine: Evolution of the treatment paradigm.

In recent years, biotechnological breakthroughs have led to identification of complex and unique biologic features associated with carcinogenesis. Tumor and cell-free DNA profiling, immune markers, and proteomic and RNA analyses are used to identify these characteristics for optimization of anticancer therapy in individual patients. Consequently, clinical trials have evolved, shifting from tumor type-centered to gene-directed, histology-agnostic, with innovative adaptive design tailored to biomarker profiling with the goal to improve treatment outcomes. A plethora of precision medicine trials have been conducted. The majority of these trials demonstrated that matched therapy is associated with superior outcomes compared to non-matched therapy across tumor types and in specific cancers. To improve the implementation of precision medicine, this approach should be used early in the course of the disease, and patients should have complete tumor profiling and access to effective matched therapy. To overcome the complexity of tumor biology, clinical trials with combinations of gene-targeted therapy with immune-targeted approaches (e.g., checkpoint blockade, personalized vaccines and/or chimeric antigen receptor T-cells), hormonal therapy, chemotherapy and/or novel agents should be considered. These studies should target dynamic changes in tumor biologic abnormalities, eliminating minimal residual disease, and eradicating significant subclones that confer resistance to treatment. Mining and expansion of real-world data, facilitated by the use of advanced computer data processing capabilities, may contribute to validation of information to predict new applications for medicines. In this review, we summarize the clinical trials and discuss challenges and opportunities to accelerate the implementation of precision oncology