Evolution and Biogeography of Haemonchus contortus: Linking Faunal Dynamics in Space and Time

History is the foundation that informs about the nuances of faunal assembly that are essential in understanding the dynamic nature of the host-parasite interface. All of our knowledge begins and ends with evolution, ecology and biogeography, as these interacting facets determine the history of biodiverse systems. These components, relating to Haemonchus, can inform about the complex history of geographical distribution, host association and the intricacies of host-parasite associations that are played out in physiological and behavioural processes that influence the potential for disease and our capacity for effective control in a rapidly changing world. Origins and evolutionary diversification among species of the genus Haemonchus and Hae- monchus contortus occurred in a complex crucible defined by shifts in environmental structure emerging from cycles of climate change and ecological perturbation during the late Tertiary and through the Quaternary. A history of sequential host colonization associated with waves of dispersal bringing assemblages of ungulates from Eurasia into Africa and processes emerging from ecosystems in collision and faunal turnover defined the arena for radiation among 12 recognized species of Haemonchus. Among congeners, the host range for H. contortus is exceptionally broad, including species among artiodactyls of 40 genera representing 5 families (and within 12 tribes of Bovi- dae). Broad host range is dramatically reflected in the degree to which translocation, introduction and invasion with host switching, has characterized an expanding distribution over time in North America, South America, southern Eurasia, Australia and New Zealand, coincidental with agriculture, husbandry and global colonization by human populations driven particularly by European exploration after the 1500s. African origins in xeric to mesic habitats of the African savannah suggest that historical constraints linked to ecological adaptations (tolerances and developmental thresholds defined by temperature and humidity for larval stages) will be substantial determinants in the potential outcomes for widespread geographical and host colonization which are predicted to unfold over the coming century. Insights about deeper evolutionary events, ecology and biogeography are critical as understanding history informs us about the possible range of responses in complex systems under new regimes of environmental forcing, especially, in this case, ecological perturbation linked to climate change. A deeper history of perturbation is relevant in understanding contemporary systems that are now strongly structured by events of invasion and colonization. The relaxation of abiotic and biotic controls on the occurrence of H. contortus, coincidental with inception and dissemination of anthelmintic resistance may be synergistic, serving to exacerbate challenges to control parasites or to limit the socioeconomic impacts of infection that can influence food security and availability. Studies of haemonchine nematodes contribute directly to an expanding model about the nature of diversity and the evolutionary trajectories for faunal assembly among complex hosteparasite systems across considerable spatial and temporal scales

Virology Experts in the Boundary Zone Between Science, Policy and the Public: A Biographical Analysis

This article aims to open up the biographical black box of three experts working in the boundary zone between science, policy and public debate. A biographical-narrative approach is used to analyse the roles played by the virologists Albert Osterhaus, Roel Coutinho and Jaap Goudsmit in policy and public debate. These figures were among the few leading virologists visibly active in the Netherlands during the revival of infectious diseases in the 1980s. Osterhaus and Coutinho in particular are still the key figures today, as demonstrated during the outbreak of novel influenza A (H1N1). This article studies the various political and communicative challenges and dilemmas encountered by these three virologists, and discusses the way in which, strategically or not, they handled those challenges and dilemmas during the various stages of the field’s recent history. Important in this respect is their pursuit of a public role that is both effective and credible. We will conclude with a reflection on the H1N1 pandemic, and the historical and biographical ties between emerging governance arrangements and the experts involved in the development of such arrangements

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin