A Porcine Model of Zika Virus Infection to Profile the In Utero Interferon Alpha Response.

Pigs are highly relevant to model human in utero Zika virus (ZIKV) infection because both species have similar physiology, genetics, immunity, fetal brain development, and postnatal brain growth. The virus causes persistent in utero infection and replicates in the fetal brain, fetal membranes, and placenta. Subclinical persistent in utero infection in mid-gestation also increases interferon alpha (IFN-α) levels in fetal blood plasma and amniotic fluid. Moreover, we demonstrated altered IFN-α responses in porcine offspring affected with subclinical in utero ZIKV infection. Elevated levels of in utero type I interferons were suggested to play a role in fetal pathology. Thus, the porcine model may provide an understanding of ZIKV-induced immunopathology in fetuses and sequelae in offspring, which is important for the development of targeted interventions. Here, we describe surgery, ultrasound-guided in utero injection, postoperative monitoring, sampling, and cytokine testing protocols.

Dispersion, colonization and phenotypic structure of prehistoric human populations of the Andes of North-Western Argentina.

In this article we study the phenotypic structure, biological relationships and evolutionary factors that acted on the biological diversity observed in the prehistoric groups that inhabited Northwest Argentina (NWA). The collections used belong to different subareas and periods of the development of this region. In this study 15 metric traits of the skull were used. To achieve the proposed objective, models derived from population genetics, multivariate statistical analysis, geo-referenced map and phenotypic correlation between geographical and biological distances were applied. The total genetic divergence (FST) is 16% and within subregions it varies between 2% and 10%. The correlation (r) between geographic and phenotypic distances among all samples in NWA is 0.3 and within subregions it varies between -0.16 (Quebrada de Humahuaca) and 0.7 (Puna de Jujuy). The analysis of georeferenced data indicates two phenotypic gradients in NWA. The results show a varied evolutionary scenario, characterized by an important population structure produced by a set of evolutionary factors (genetic isolation, non-random mating, effective size and different rates of genetic interaction between subpopulations).

S/MAR Element Facilitates Episomal Long-Term Persistence of Adeno-Associated Virus Vector Genomes in Proliferating Cells.

Adeno-associated virus (AAV) vectors are one of the most frequently applied gene transfer systems in research and human clinical trials. Since AAV vectors do not possess an integrase activity, application is restricted to terminally differentiated tissues if transgene expression is required long term. To overcome this limitation and to generate AAV vectors that persist episomally in dividing cells, AAV vector genomes were equipped with a scaffold/matrix attachment region (S/MAR). After a mild antibiotic selection, cells transduced with AAV-S/MAR established colonies that maintained long-term transgene expression (>50 population doublings) from replicating AAV vector episomes in the absence of further selection. Unexpectedly, with a lesser but still significant efficiency, the control vector (AAV-ΔS/MAR), a standard single-stranded AAV vector, also established stable transgene-expressing colonies, most of which were maintained as replicating episomes rather than integrated vector genomes. Thus, based on the result in HeLa cells, it is concluded that AAV vector genomes per se possess the ability to establish episomal maintenance in proliferating cells, a feature that can be enhanced by incorporation of a foreign genomic element such as an S/MAR element.

Coastal, valley, and oasis interaction: impact on the evolution of ancient populations in the South Central Andes.

The existing biocultural links are analyzed among ancient inhabitants of the Cochabamba valleys (Bolivia) from the Formative and Tiwanaku periods, coastal and inland Azapa region (Chile) from the Late Archaic to the Late periods, and the Atacama Desert oases (Chile) from the Formative period to the time of European contact. Craniometric information obtained from a sample of 565 individuals from different sites of the studied regions was evaluated using methods derived from quantitative genetics and multivariate statistical analysis techniques. It is shown that during the Formative and Tiwanaku periods inhabitants of the Cochabamba valleys maintained contact with the population of northern Chile. This contact was more fluid with the people from the interior valley of Azapa than it was with the settlers of San Pedro Atacama (SPA). An important biological affinity in the Late Period between the inhabitants of the Azapa valley and the late SPA groups is also examined. The Late-Inca Catarpe SPA sample shows a broad genetic variability shared with the majority of the groups studied. The results reaffirm the differences between the coastal and interior Azapa valley groups and strengthen the hypothesis of two pathways to populating the south central Andean area. The divergence observed among subpopulations can be explained by the spatiotemporal dispersion between them, genetic drift dispersion compensated by the action of gene flow, and cultural norms that regulate within group mating.

A comparison of florfenicol and tulathromycine for the treatment of undifferentiated fever in feedlot calves.

The purpose of this study was to compare the relative cost-effectiveness of florfenicol with that of tulathromycin for treatment of undifferentiated fever (UF) in feedlot calves at ultra-high risk of developing UF that receive metaphylactic tulathromycin on arrival at the feedlot. Calves that received therapeutic florfenicol had lower overall mortality (P=.045) and bovine respiratory disease mortality (P=.050) compared with calves that received therapeutic tulathromycin, but no significant differences were detected in feedlot performance, carcass characteristics, or other animal health variables. There was a net advantage of Can$41.19/treated animal in the florfenicol group versus the tulathromycin group. This study demonstrates that it is more cost-effective to use florfenicol than tulathromycin for the initial treatment of UF in feedlot calves at ultra-high risk of developing UF that receive on-arrival metaphylactic tulathromycin.