The Restriction of Zoonotic PERV Transmission by Human APOBEC3G

The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections

Along‐stream, seasonal, and interannual variability of the North Icelandic Irminger Current and East Icelandic Current around Iceland

Data from repeat hydrographic surveys over the 25-year period 1993 to 2017, together with satellite altimetry data, are used to quantify the temporal and spatial variability of the North Icelandic Irminger Current (NIIC), East Icelandic Current (EIC), and the water masses they advect around northern Iceland. We focus on the warm, salty Atlantic Water (AW) flowing northward through Denmark Strait and the cooler, fresher, denser Atlantic-origin Overflow Water (AtOW) which has circulated cyclonically around the rim of the Nordic Seas before being advected to the Iceland slope via the EIC. The absolute geostrophic velocities reveal that approximately half of the NIIC recirculates just north of Denmark Strait, while the remaining half merges with the EIC to form a single current that extends to the northeast of Iceland, with no further loss in transport of either component. The AW percentage decreases by 75% over this distance, while the AtOW percentage is higher than that of the AW in the merged current. The NIIC and merged NIIC-EIC are found to be baroclinically unstable, which causes the flow to become increasingly barotropic as it progresses around Iceland. A seasonal accounting of the water masses within the currents indicates that only in springtime is the NIIC dominated by AW inflow north of Denmark Strait. Overall, there is considerably more seasonal and along-stream variability in the properties of the flow prior to the merging of the NIIC and EIC. Over the 25-year time period, the NIIC became warmer, saltier, and increased in volume transport

Mapping co-ancestry connections between the genome of a Medieval individual and modern Europeans

Historical genetic links among similar populations can be difficult to establish. Identity by descent (IBD) analyses find genomic blocks that represent direct genealogical relationships among individuals. However, this method has rarely been applied to ancient genomes because IBD stretches are progressively fragmented by recombination and thus not recognizable after few tens of generations. To explore such genealogical relationships, we estimated long IBD blocks among modern Europeans, generating networks to uncover the genetic structures. We found that Basques, Sardinians, Icelanders and Orcadians form, each of them, highly intraconnected sub-clusters in a European network, indicating dense genealogical links within small, isolated populations. We also exposed individual genealogical links -such as the connection between one Basque and one Icelandic individual- that cannot be uncovered with other, widely used population genetics methods such as PCA or ADMIXTURE. Moreover, using ancient DNA technology we sequenced a Late Medieval individual (Barcelona, Spain) to high genomic coverage and identified IBD blocks shared between her and modern Europeans. The Medieval IBD blocks are statistically overrepresented only in modern Spaniards, which is the geographically closest population. This approach can be used to produce a fine-scale reflection of shared ancestry across different populations of the world, offering a direct genetic link from the past to the present.This research was supported by a PGC2018-0955931-B-100 grant (MCIU/AEI/FEDER, UE) of Spain to C.L.-F., by a grant from MINECO (FIS2016-77447-R) to S.C. and by 2017SGR 00622 grant from Generalitat de Catalunya’s Agency (AGAUR) to S.C. Sequences from the Medieval genome are deposited at the European Nucleotide Archives under accession number PRJEB33120

The origin and evolution of maize in the Southwestern United States

The origin of maize (Zea mays mays) in the US Southwest remains contentious, with conflicting archaeological data supporting either coastal1,​2,​3,​4 or highland5,6 routes of diffusion of maize into the United States. Furthermore, the genetics of adaptation to the new environmental and cultural context of the Southwest is largely uncharacterized7. To address these issues, we compared nuclear DNA from 32 archaeological maize samples spanning 6,000 years of evolution to modern landraces. We found that the initial diffusion of maize into the Southwest about 4,000 years ago is likely to have occurred along a highland route, followed by gene flow from a lowland coastal maize beginning at least 2,000 years ago. Our population genetic analysis also enabled us to differentiate selection during domestication for adaptation to the climatic and cultural environment of the Southwest, identifying adaptation loci relevant to drought tolerance and sugar content.No Full Tex

Peptide Folding in Cellular Environments: A Monte Carlo and Markov Modeling Approach

Steric interactions with surrounding macromolecules tend to favor the compact native state of a globular protein over its unfolded state. However, in experiments conducted in cells and concentrated protein solutions, both stabilization and destabilization of proteins have been observed, compared to dilute-solution conditions. Therefore, in order to understand the effects of surrounding macromolecules on protein properties such as stability, there is a need for computational modeling beyond the level of hard-sphere crowders. Here, we discuss some recent exploratory studies of peptide folding in the presence of explicit protein crowders, carried out by us using an all-atom Monte Carlo-based approach along with an implicit solvent force field. For interpreting the simulation data, time-lagged independent component analysis and Markov state modeling are used