Hiding in plain sight: discovery and phylogeography of a cryptic species of Trichinella (Nematoda: Trichinellidae) in wolverine (Gulo gulo)

Understanding parasite diversity and distribution is essential in managing the potential impact of para- sitic diseases in animals and people. Imperfect diagnostic methods, however, may conceal cryptic species. Here, we report the discovery and phylogeography of a previously unrecognized species of Trichinella in wolverine (Gulo gulo) from northwestern Canada that was indistinguishable from T. nativa using the stan- dard multiplex PCR assay based on the expansion segment 5 (ESV) of ribosomal DNA. The novel genotype, designated as T13, was discovered when sequencing the mitochondrial genome. Phylogenetic analyses of the mitochondrial genome and of 15 concatenated single-copy orthologs of nuclear DNA indicated a com- mon ancestor for the encapsulated clade is shared by a subclade containing Trichinella spiralis and Trichinella nelsoni, and a subclade containing T13 and remaining taxa: T12 + (T2 + T6) + [(T5 + T9) + (T 3 + T8)]. Of 95 individual hosts from 12 species of mammalian carnivores from northwestern Canada from which larvae were identified as T. nativa on multiplex PCR, only wolverines were infected with T13 (14 of 42 individuals). These infections were single or mixed with T. nativa and/or T6. Visual examination and motility testing confirmed that T13 is encapsulated and likely freeze-tolerant. We developed a new Polymerase Chain Reaction-Restriction Fragment Length Polymorphism which unequivocally distinguishes between T13 and T. nativa. We propose Trichinella chanchalensis n. sp. for T13, based on significant genetic divergence from other species of Trichinella and broad-based sampling of the Trichinella genome. Exploration of Alaskan and Siberian isolates may contribute to further resolution of a phylogeo- graphically complex history for species of Trichinella across Beringia, including Trichinella chanchalensis n. sp. (T13

Characteristics of the National Applicant Pool for Clinical Informatics Fellowships (2016-2017)

We conducted a national study to assess the numbers and diversity of applicants for 2016 and 2017 clinical informatics fellowship positions. In each year, we collected data on the number of applications that programs received from candidates who were ultimately successful vs. unsuccessful. In 2017, we also conducted an anonymous applicant survey. Successful candidates applied to an average of 4.2 and 5.5 programs for 2016 and 2017, respectively. In the survey, unsuccessful candidates reported applying to fewer programs. Assuming unsuccessful candidates submitted between 2-5 applications each, the total applicant pool numbered 42-69 for 2016 (competing for 24 positions) and 52-85 for 2017 (competing for 30 positions). Among survey respondents (n=33), 24% were female, 1 was black and none were Hispanic. We conclude that greater efforts are needed to enhance interest in clinical informatics among medical students and residents, particularly among women and members of underrepresented minority groups

Standard care versus protocol based therapy for new onset Pseudomonas aeruginosa in cystic fibrosis: Protocol-Based Anti-PseudomonalTherapy in CF

The Early Pseudomonal Infection Control (EPIC) randomized trial rigorously evaluated the efficacy of different antibiotic regimens for eradication of newly identified Pseudomonas (Pa) in children with cystic fibrosis (CF). Protocol based therapy in the trial was provided based on culture positivity independent of symptoms. It is unclear whether outcomes observed in the clinical trial were different than those that would have been observed with historical standard of care driven more heavily by respiratory symptoms than culture positivity alone. We hypothesized that the incidence of Pa recurrence and hospitalizations would be significantly reduced among trial participants as compared to historical controls whose standard of care preceded the widespread adoption of tobramycin inhalation solution (TIS) as initial eradication therapy at the time of new isolation of Pa

Initial sequencing and analysis of the human genome

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62798/1/409860a0.pd

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

“Emerging” Parasitic Infections in Arctic Ungulates

Important drivers for emergence of infectious disease in wildlife include changes in the environment, shrinking habitats or concentration of wildlife, and movement of people, animals, pathogens, or vectors. In this paper we present three case-studies of emerging parasitic infections and diseases in ungulates in the Canadian north. First we discuss climate warming as an important driver for the emergence of disease associated with Umingmakstrongylus pallikuukensis, a nematode lungworm of muskoxen. Then we examine how Protostrongylus stilesi, the sheep lungworm, emerged (or re-emerged) in muskoxen after re-introduction of this host into its historical range made it sympatric with Dall’s sheep. Finally, we consider Teladorsagia boreoarcticus, a newly described and common abomasal nematode of muskoxen that is emerging as a disease-causing parasite and may be an important regulator for muskox populations on Banks Island, Northwest Territories. These and other arctic host-parasite systems are exquisitely tuned and constrained by a harsh and highly seasonal environment. The dynamics of these systems will be impacted by climate change and other ecological disruptions. Baseline knowledge of parasite biodiversity and parasite and host ecology, together with predictive models and long-term monitoring programs, are essential for anticipating and detecting altered patterns of host range, geographic distribution, and the emergence of parasitic infections and diseases

\u3ci\u3eProtostrongylus stilesi\u3c/i\u3e (Nematoda: Protostrongylidae): Ecological Isolation and Putative Host-Switching Between Dall’s Sheep and Muskoxen in a Contact Zone

The occurrence of Protostrongylus stilesi in a population of introduced muskoxen, Ovibos moschatus wardi, on the Arctic Coastal Plain, Yukon Territory (YT) and Northwest Territories (NT), Canada, is consistent with a contemporary colonization event from Dall’s sheep, Ovis dalli dalli, which indicates that host specificity may be ecologically based and contextual for this parasite. Colonization of muskoxen by P. stilesi may be a predictable event in zones of sympatry with Dall’s sheep; exposure to infection may coincide with occupation of winter ranges of Dall’s sheep by muskoxen during the summer season. Disruption of contemporary ecological isolating barriers can result from anthropogenically or climatologically driven habitat perturbation, and result from management practices that influence the distribution of ungulate hosts. Thus, if zones of contact become more extensive or the temporal limits on allopatry are relaxed, we may observe increasing instances of host switching by parasites or pathogens at the interface of newly emerging ecotones. Impacts to northern systems linked to climatologically and anthropogenically driven global change and the effects of management must be tracked within the context of biodiversity survey and inventory and archival collections, as foundations for monitoring ecosystem-level perturbations. A developing interface for muskoxen, wild sheep, and parasites along the Mackenzie River ecotone represents a natural model or field laboratory to examine these processes. Additonally, lungworms, Protostrongylus spp., had not been reported in muskoxen, and a new geographic record for this nematode was established in Dall’s sheep from the northern Richardson Mountains, NT