A multi-species functional embedding integrating sequence and network structure

A key challenge to transferring knowledge between species is that different species have fundamentally different genetic architectures. Initial computational approaches to transfer knowledge across species have relied on measures of heredity such as genetic homology, but these approaches suffer from limitations. First, only a small subset of genes have homologs, limiting the amount of knowledge that can be transferred, and second, genes change or repurpose functions, complicating the transfer of knowledge. Many approaches address this problem by expanding the notion of homology by leveraging high-throughput genomic and proteomic measurements, such as through network alignment. In this work, we take a new approach to transferring knowledge across species by expanding the notion of homology through explicit measures of functional similarity between proteins in different species. Specifically, our kernel-based method, HANDL (Homology Assessment across Networks using Diffusion and Landmarks), integrates sequence and network structure to create a functional embedding in which proteins from different species are embedded in the same vector space. We show that inner products in this space and the vectors themselves capture functional similarity across species, and are useful for a variety of functional tasks. We perform the first whole-genome method for predicting phenologs, generating many that were previously identified, but also predicting new phenologs supported from the biological literature. We also demonstrate the HANDL embedding captures pairwise gene function, in that gene pairs with synthetic lethal interactions are significantly separated in HANDL space, and the direction of separation is conserved across species. Software for the HANDL algorithm is available at http://bit.ly/lrgr-handl.Published versio

Whole genome sequencing of experimental hybrids supports meiosis-like sexual recombination in Leishmania

Hybrid genotypes have been repeatedly described among natural isolates of Leishmania, and the recovery of experimental hybrids from sand flies co-infected with different strains or species of Leishmania has formally demonstrated that members of the genus possess the machinery for genetic exchange. As neither gamete stages nor cell fusion events have been directly observed during parasite development in the vector, we have relied on a classical genetic analysis to determine if Leishmania has a true sexual cycle. Here, we used whole genome sequencing to follow the chromosomal inheritance patterns of experimental hybrids generated within and between different strains of L. major and L. infantum. We also generated and sequenced the first experimental hybrids in L. tropica. We found that in each case the parental somy and allele contributions matched the inheritance patterns expected under meiosis 97–99% of the time. The hybrids were equivalent to F1 progeny, heterozygous throughout most of the genome for the markers that were homozygous and different between the parents. Rare, non-Mendelian patterns of chromosomal inheritance were observed, including a gain or loss of somy, and loss of heterozygosity, that likely arose during meiosis or during mitotic divisions of the progeny clones in the fly or culture. While the interspecies hybrids appeared to be sterile, the intraspecies hybrids were able to produce backcross and outcross progeny. Analysis of 5 backcross and outcross progeny clones generated from an L. major F1 hybrid, as well as 17 progeny clones generated from backcrosses involving a natural hybrid of L. tropica, revealed genome wide patterns of recombination, demonstrating that classical crossing over occurs at meiosis, and allowed us to construct the first physical and genetic maps in Leishmania. Altogether, the findings provide strong evidence for meiosis-like sexual recombination in Leishmania, presenting clear opportunities for forward genetic analysis and positional cloning of important genes.</div

Molecular evidence for Anaplasma phagocytophilum in Israel

Sequences from the Anaplasma phagocytophilum 16S rRNA gene were detected in 5 ticks representing 3 species (Hyalomma marginatum, Rhipicephalus turanicus, and Boophilus kohlsi) collected from roe deer (Capreolus capreolus) in Mount Carmel, Israel. The sequences were all identical to those of Ap-variant 1 strain

Promoting independence in Lewy body dementia through exercise: the PRIDE study

Background: Lewy body dementia (LBD) is an aggressive type of dementia of rapid, fluctuating disease trajectory, higher incidence of adverse events, and poorer functional independence than observed in Alzheimer’s disease dementia. Non-pharmacological treatments such as progressive, high-intensity exercise are effective in other neurological cohorts but have been scarcely evaluated in LBD. Methods: The Promoting Independence in Lewy Body Dementia through Exercise (PRIDE) trial was a non-randomised, non-blinded, crossover pilot trial involving older adults with LBD consisting of a baseline assessment, an 8-week wait-list, and an 8-week exercise intervention. The aims of this study were to evaluate the determinants of the primary outcome functional independence, as measured by the Movement Disorder Society Unified Parkinson’s Disease Rating Scale, and the feasibility and preliminary efficacy of an exercise intervention on this outcome. Additionally, important clinical characteristics were evaluated to explore associations and treatment targets. The exercise intervention was supervised, clinic-based, high-intensity progressive resistance training (PRT), challenging balance, and functional exercises, 3 days/week. Results: Nine participants completed the baseline cross-sectional study, of which five had a diagnosis of Parkinson’s disease dementia (PDD), and four dementia with Lewy Bodies (DLB). Six completed the exercise intervention (three PDD, three DLB). The cohort was diverse, ranging from mild to severe dementia and living in various residential settings. Greater functional independence at baseline was significantly associated with better physical function, balance, cognition, quality of life, muscle mass ratio, walking endurance, faster walking speed and cadence, and lower dementia severity (p 80% adherence), and only one minor exercise-related adverse event occurred. Conclusions: PRIDE is the first exercise trial conducted specifically within individuals diagnosed with LBD, and provides important insight for the design of larger, randomized trials for further evaluation of progressive, high-intensity exercise as a valuable treatment in LBD. Trial registration: The PRIDE trial protocol has previously been prospectively registered (08/04/2016, ANZCTR: ACTRN12616000466448)

Andean Land Use And Biodiversity: Humanized Landscapes In A Time Of Change

Some landscapes Cannot be understood without reference., to the kinds. degrees, kinds, degrees, and history of human-caused modifications to the Earth's surface. The tropical latitudes of the Andes represent one such place, with agricultural land-use systems appearing in the Early Holocene. Current land use includes both intensive and extensive grazing and crop- or tree-based agricultural systems found across virtually the, entire range of possible elevations and humidity regimes. Biodiversity found in or adjacent to such humanized landscapes will have been altered in abundance. composition, and distribution in relation to the resiliency of the native Species to harvest, hold cover modifications, and other deliberate or inadvertent human land uses. In addition, the geometries of land cover, resulting flout difference among the shapes, sizes, connectivities, and physical structures of the patches, corridors, and matrices that compose landscape mosaics, will constrain biodiversity, often in predictable ways. This article proposes a conceptual model that alter ins that the Continued persistence of native species may depend as much oil the shifting Of Andean landscape mosaics as on species characteristics, themselves. Furthermore, mountains such as the Andes display long gradients of environmental Conditions that after in relation to latitude, soil moisture, aspect, and elevation. Global environmental change will shift these, especially temperature and humidity regimes along elevational gradients, causing Changes outside the historical range of variation for some species. Both land-use systems and Conservation efforts will need to respond spatially to these shifts in the future, at both landscape and regional scales.Geography and the Environmen

Self-hybridization in Leishmania major

Genetic exchange between differen

Is the Relationship Between Pathogen Avoidance and Ideological Conservatism Explained by Sexual Strategies?

Multiple recent studies report that measures of pathogen avoidance (e.g., disgust sensitivity) correlate with political ideology. This relationship has been interpreted as suggesting that certain political views (specifically, those views that are categorized as socially conservative) function to mitigate the pathogen threats posed either by intergroup interactions or by departures from traditional societal norms, which sometimes evolve culturally for anti-pathogen functions. We propose and test the alternative hypothesis that pathogen avoidance relates to conservatism indirectly via sexual strategies (e.g., relatively monogamous versus relatively promiscuous). Specifically, we argue that individuals who are more invested in avoiding pathogens follow a more monogamous mating strategy to mitigate against pathogens transmitted during sexual contact, and individuals following a more monogamous mating strategy adopt socially conservative political ideologies to support their reproductive interests. Results from three studies ( N's = 819, 238, and 248) using multiple measures of pathogen avoidance, sexual strategies, and ideology support this account, with sexual strategies fully mediating the relationship between measures of pathogen avoidance and conservatism in each study

Effects of pressure on diffusion and vacancy formation in MgO from non-empirical free-energy integrations

The free energies of vacancy pair formation and migration in MgO were computed via molecular dynamics using free-energy integrations and a non-empirical ionic model with no adjustable parameters. The intrinsic diffusion constant for MgO was obtained at pressures from 0 to 140 GPa and temperatures from 1000 to 5000 K. Excellent agreement was found with the zero pressure diffusion data within experimental error. The homologous temperature model which relates diffusion to the melting curve describes well our high pressure results within our theoretical framework.Comment: 4 pages, latex, 1 figure, revtex, submitted to PR