Exportation of Monkeypox Virus From the African Continent.

BACKGROUND: The largest West African monkeypox outbreak began September 2017, in Nigeria. Four individuals traveling from Nigeria to the United Kingdom (n = 2), Israel (n = 1), and Singapore (n = 1) became the first human monkeypox cases exported from Africa, and a related nosocomial transmission event in the United Kingdom became the first confirmed human-to-human monkeypox transmission event outside of Africa. METHODS: Epidemiological and molecular data for exported and Nigerian cases were analyzed jointly to better understand the exportations in the temporal and geographic context of the outbreak. RESULTS: Isolates from all travelers and a Bayelsa case shared a most recent common ancestor and traveled to Bayelsa, Delta, or Rivers states. Genetic variation for this cluster was lower than would be expected from a random sampling of genomes from this outbreak, but data did not support direct links between travelers. CONCLUSIONS: Monophyly of exportation cases and the Bayelsa sample, along with the intermediate levels of genetic variation, suggest a small pool of related isolates is the likely source for the exported infections. This may be the result of the level of genetic variation present in monkeypox isolates circulating within the contiguous region of Bayelsa, Delta, and Rivers states, or another more restricted, yet unidentified source pool

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Back to the Grindstone? The Archaeological Potential of Grinding-Stone Studies in Africa with Reference to Contemporary Grinding Practices in Marakwet, Northwest Kenya

This article presents observations on grinding-stone implements and their uses in Elgeyo-Marakwet County, northwest Kenya. Tool use in Marakwet is contextualized with a select overview of literature on grinding-stones in Africa. Grinding-stones in Marakwet are incorporated not only into quotidian but also into more performative and ritual aspects of life. These tools have distinct local traditions laden with social as well as functional importance. It is argued that regionally and temporally specific studies of grinding-stone tool assemblages can be informative on the processing of various substances. Despite being common occurrences, grinding-stone tools are an under-discussed component of many African archaeological assemblages. Yet the significance of grinding-stones must be reevaluated, as they hold the potential to inform on landscapes of past food and material processing

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Data from: Multilocus characterization of a woodrat (genus Neotoma) hybrid zone

In order to investigate hybridization between 2 species of woodrats, Neotoma floridana and Neotoma micropus, 103 specimens were collected, in March of 1988, from a known area of sympatry, and compared with reference collections from areas of allopatry. Ten genetic markers, consisting of 7 microsatellite loci, 1 mitochondrial gene (cytochrome-b [Cytb]), and 2 nuclear introns (intron 2 of the vertebrate alcohol dehydrogenase gene [Adh1-I2] and intron 7 of the beta-fibrinogen gene [Fgb-I7]) were used to develop a composite genotype for each individual and for detection of hybridization. Six individuals were identified as pure parental N. micropus, 96 as hybrids, and 1 as pure parental N. floridana. Hybrids were formed primarily through matings between complex genotypes, resulting in a high prevalence of individuals classified as backcrosses. The ratio of hybrid classes, population substructure, and presence of significant linkage disequilibrium within the zone of contact could not reject either the hybrid superiority or hybrid equilibrium model as responsible for maintenance of this hybrid zone. The collection date of this dataset (1988) provided not only a point in time assessment of the hybrid zone but also provided opportunities for future comparisons of temporal datasets with the purpose of examining hybrid zone characteristics over multiple generations

Molecular systematics of South American marsh rats of the genus Holochilus (Muroidea, Cricetidae, Sigmodontinae)

We present a comprehensive systematic study of Holochilus, a sigmodontine genus of large, herbivorous, and semiaquatic rodents widely distributed in South America. Remarkably, given its complex taxonomic history and large economic as well as epidemiological importance, the alpha taxonomy of Holochilus has not benefited from a molecular-based approach. The study is based on sequences of 1 mitochondrial and 3 nuclear loci that were analyzed by maximum likelihood and Bayesian inference. Analyses include sequences of specimens from localities from Argentina, Bolivia, Brazil, Colombia, Paraguay, Peru, Suriname, and Uruguay, representing all but 2 of the species currently recognized in the genus. Of the 4 data matrices, the mitochondrial data set contains the largest geographic coverage and recovered 6 species-level lineages that form 2 well-supported species groups: the brasiliensis species group formed by H. brasiliensis and H. vulpinus and the sciureus species group composed by H. chacarius, H. sciureus, and 2 currently unnamed forms. Surprisingly, in the cytochrome b gene analyses, the 2 species groups are not sister to each other; i.e., Holochilus is not monophyletic, although these topologies lack significant support. However, the monophyly of Holochilus was supported by the 3 nuclear loci as well as by the combined analysis of all 4 loci. These genealogical results are the basis of taxonomic and biogeographic considerations.Presentamos un estudio sistemático comprensivo sobre Holochilus, un género sigmodontino de grandes roedores herbívoros y semi-acuáticos ampliamente distribuido en América del Sur. Llamativamente, dada su compleja historia taxonómica y el gran impacto económico y epidemiológico, la taxonomía alfa de Holochilus no se ha beneficiado de un abordaje basado en evidencia molecular. El estudio se basa en secuencias de 1 gen mitocondrial y de 3 nucleares que fueron analizadas con máxima verosimilitud e inferencia Bayesiana. Los análisis incluyen secuencias de especímenes colectados en localidades de Argentina, Bolivia, Brasil, Colombia, Paraguay, Perú, Surinam y Uruguay, representando todas, con excepción de 2, las especies actualmente reconocidas en el género. La genealogía mitocondrial, que es la que tiene la mayor cobertura geográfica de Holochilus, recobra 6 linajes de nivel de especie que forman 2 grupos de especies bien apoyados: el grupo de especies brasiliensis integrado por H. brasiliensis y H. vulpinus y el grupo de especies sciureus que está compuesto por H. chacarius, H. sciureus y 2 formas aparentemente sin nominar. Llamativamente, en los análisis basados en el gen mitocondrial los 2 grupos de especies no son hermanos; i.e., Holochilus no es monofilético, aunque esta topología no tiene apoyo significativo. Sin embargo la monofilia de Holochilus es apoyada por los análisis de los 3 genes nucleares y por el análisis combinado de los 4 genes. Estos resultados genealógicos son la base de consideraciones taxonómicas y biogeográficas.Fil: D'elía, Guillermo. Universidad Austral de Chile; ChileFil: Hanson, J. Delton. RTL Genomics; Estados UnidosFil: Mauldin, Matthew R.. Centers for Disease Control and Prevention; Estados UnidosFil: Teta, Pablo Vicente. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales ; ArgentinaFil: Pardiñas, Ulises Francisco J.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Diversidad y Evolución Austral; Argentin

Mauldin et al Microsatellite Data Dryad

This file contains all microsatellite data examined in the study. The first row contains column headers. The first column contains museum ID numbers. All following columns indicate allele sizes for the animal indicated at the beginning of the row. Missing data value is coded as "0