Associations among Habitat Characteristics and Meningeal Worm Prevalence in Eastern South Dakota, USA

Few studies have evaluated how wetland and forest characteristics influence the prevalence of meningeal worm (Parelaphostrongylus tenuis) infection of deer throughout the grassland biome of central North America. We used previously collected, county-level prevalence data to evaluate associations between habitat characteristics and probability of meningeal worm infection in white-tailed deer (Odocoileus virginianus) across eastern South Dakota, US. The highest-ranked binomial regression model for detecting probability of meningeal worm infection was spring temperature + summer precipitation + percent wetland; weight of evidence (wi=0.71) favored this model over alternative models, though predictive capability was low (Receiver operating characteristic=0.62). Probability of meningeal worm infection increased by 1.3- and 1.6-fold for each 1-cm and 1-C increase in summer precipitation and spring temperature, respectively. Similarly, probability of infection increased 1.2-fold for each 1% increase in wetland habitat. Our findings highlight the importance of wetland habitat in predicting meningeal worm infection across eastern South Dakota. Future research is warranted to evaluate the relationships between climatic conditions (e.g., drought, wet cycles) and deer habitat selection in maintaining P. tenuis along the western boundary of the parasite

Influence of ecologic factors on prevalence of meningeal worm (Parelaphostrongylus tenuis) infection in South Dakota, USA

The meningeal worm (Parelaphostrongylus tenuis) is a nematode parasite that commonly infects white-tailed deer (Odocoileus virginianus; WTD) throughout the deciduous forest biome and deciduous-coniferous ecotone of eastern and central North America; the species is not known to occur west of the grassland biome of central North America. We used county-specific prevalence data to evaluate potential effects of landscape and climatologic factors on the spatial distribution of meningeal worm infection in South Dakota, US. Probability of infection increased 4-fold between eastern and western South Dakota and 1.3-fold for each 1-cm increase in summer precipitation. Sixty-three percent of WTD had only a single worm in the cranium. Expansion of meningeal worm infection across western South Dakota may be inherently low due to the combined effects of arid climate and potential attributes of the Missouri River that limit regional movements by infected WTD. Use of landscape genetic analyses to identify potential relationships between landscape features and population genetic structure of infected deer and parasites may contribute to a greater understanding of regional heterogeneity in meningeal worm infection rates across South Dakota, particularly in counties adjacent to the Missouri River. Future research evaluating heterogeneity in prevalence and intensity of infection between fawn and yearling deer, and the potential role of yearling male deer as dispersal agents of meningeal worms across the Missouri River, also is warranted

Nest tree use by southern flying squirrels in fragmented Midwestern landscapes

Southern flying squirrels (Glaucomys volans; SFS) nest in naturally formed cavities in snags and hardwoods found in mature, oak (Quercus spp.)–hickory (Carya spp.) forests. Intensive forest fragmentation of the Midwest United States limits the number of available nesting trees. We quantified annual nest‐site selection patterns by southern flying squirrels across fragmented landscapes of west‐central Illinois, USA. We used radiotelemetry to measure nest‐tree use by 55 SFS (30 males, 25 females) captured during 2014–2016. Of 105 nest trees used by SFS, live trees and snags comprised 75% and 25%, respectively. Probability of diurnal nest‐tree use increased 1.08/1.00‐cm increase in diameter‐breast‐height and by 1.50/1‐unit increase in the number of overstory mast trees between random and nest‐tree habitat areas (i.e., 300‐m2 circular plots). Similarly, probability of diurnal nest‐tree use increased 1.29/1‐unit increase in the number of snags between random and nest‐tree habitat areas. Our results revealed no intersexual differences in patterns of nest‐site selection, which may reflect the tendency for SFS to compensate for reduced availability of key structural attributes (i.e., snags, overstory trees) across fragmented forests by exhibiting similar intersexual patterns of nest‐tree use. Use of natural cavities for denning is encouraging, but also underscores the importance of unharvested oak–hickory forests in contributing essential habitat to SFS populations in fragmented Midwestern landscapes

Expression in Aromatase Inhibitor Responder vs. Non-Responder HR+ Breast Cancer Cohorts

Hormone receptor positive (HR+) breast cancer patients have an excellent prognosis with over 85% cure rates. However, 20,000 women with HR+ breast cancer die annually from tumor recurrence. Those at highest risk for recurrence are those women whose tumors continue to proliferate through estrogen blockade (Figure 4). Addition of chemotherapy for these patients failed to improve outcomes. We retrospectively identified women with HR+ breast cancer treated neoadjuvantly with aromatase inhibitors (AI), and selected matched patient cohorts for responders and non-responders determined by post-AI Ki67 o

Autophagosome-based strategy to monitor apparent tumor-specific CD8 T cells in patients with prostate cancer

The immune system plays an essential role in eradicating cancer in concert with various treatment modalities. In the absence of autologous tumor material, no standardized method exists to assess T cell responses against the many antigens that may serve as cancer rejection antigens. Thus, development of methods to screen for therapy-induced anti-tumor responses is a high priority that could help tailor therapy. Here we tested whether a tumor-derived antigen source called DRibbles®, which contain a pool of defective ribosomal products (DRiPs), long-lived and short-lived proteins (SLiPs) and danger-associated molecular patterns (DAMPs), can be used to identify tumor-associated antigen (TAA)-specific responses in patients before or after immunotherapy treatment. Protein content, gene expression and non-synonymous – single nucleotide variants (ns-SNVs) present in UbiLT3 DRibbles were compared with prostate adenocarcinomas and the prostate GVAX vaccine cell lines (PC3/LNCaP). UbiLT3 DRibbles were found to share proteins, as well as match tumor sequences for ns-SNVs with prostate adenocarcinomas and with the cell lines PC3 and LNCaP. UbiLT3 DRibbles were used to monitor anti-tumor responses in patients vaccinated with allogeneic prostate GVAX. UbiLT3-DRibble-reactive CD8+ T-cell responses were detected in post-vaccine PBMC of 6/12 patients (range 0.85–22% of CD8+ cells) after 1 week in vitro stimulation (p = 0.007 vs. pre-vaccine). In conclusion, a cancer-derived autophagosome-enriched preparation, packaging over 100 proteins over-expressed in prostate cancer into microvesicles containing DAMPs, could be used to identify CD8+ T cells in peripheral blood from patients after prostate GVAX vaccination and may represent a general method to monitor anti-cancer T cell responses following immunotherapy

Single nucleotide polymorphisms (SNPs) distinguish Indian-origin and Chinese-origin rhesus macaques (Macaca mulatta)

BACKGROUND: Rhesus macaques serve a critical role in the study of human biomedical research. While both Indian and Chinese rhesus macaques are commonly used, genetic differences between these two subspecies affect aspects of their behavior and physiology, including response to simian immunodeficiency virus (SIV) infection. Single nucleotide polymorphisms (SNPs) can play an important role in both establishing ancestry and in identifying genes involved in complex diseases. We sequenced the 3' end of rhesus macaque genes in an effort to identify gene-based SNPs that could distinguish between Indian and Chinese rhesus macaques and aid in association analysis. RESULTS: We surveyed the 3' end of 94 genes in 20 rhesus macaque animals. The study included 10 animals each of Indian and Chinese ancestry. We identified a total of 661 SNPs, 457 of which appeared exclusively in one or the other population. Seventy-nine additional animals were genotyped at 44 of the population-exclusive SNPs. Of those, 38 SNPs were confirmed as being population-specific. CONCLUSION: This study demonstrates that the 3' end of genes is rich in sequence polymorphisms and is suitable for the efficient discovery of gene-linked SNPs. In addition, the results show that the genomic sequences of Indian and Chinese rhesus macaque are remarkably divergent, and include numerous population-specific SNPs. These ancestral SNPs could be used for the rapid scanning of rhesus macaques, both to establish animal ancestry and to identify gene alleles that may contribute to the phenotypic differences observed in these populations

Single Nucleotide Polymorphisms (SNPs) Distinguish Indian-Origin and Chinese-Origin Rhesus Macaques (Macaca Mulatta)

BACKGROUND: Rhesus macaques serve a critical role in the study of human biomedical research. While both Indian and Chinese rhesus macaques are commonly used, genetic differences between these two subspecies affect aspects of their behavior and physiology, including response to simian immunodeficiency virus (SIV) infection. Single nucleotide polymorphisms (SNPs) can play an important role in both establishing ancestry and in identifying genes involved in complex diseases. We sequenced the 3\u27 end of rhesus macaque genes in an effort to identify gene-based SNPs that could distinguish between Indian and Chinese rhesus macaques and aid in association analysis. RESULTS: We surveyed the 3\u27 end of 94 genes in 20 rhesus macaque animals. The study included 10 animals each of Indian and Chinese ancestry. We identified a total of 661 SNPs, 457 of which appeared exclusively in one or the other population. Seventy-nine additional animals were genotyped at 44 of the population-exclusive SNPs. Of those, 38 SNPs were confirmed as being population-specific. CONCLUSION: This study demonstrates that the 3\u27 end of genes is rich in sequence polymorphisms and is suitable for the efficient discovery of gene-linked SNPs. In addition, the results show that the genomic sequences of Indian and Chinese rhesus macaque are remarkably divergent, and include numerous population-specific SNPs. These ancestral SNPs could be used for the rapid scanning of rhesus macaques, both to establish animal ancestry and to identify gene alleles that may contribute to the phenotypic differences observed in these populations

Transcriptional and immunohistological assessment of immune infiltration in pancreatic cancer.

Pancreatic adenocarcinoma is characterized by a complex tumor environment with a wide diversity of infiltrating stromal and immune cell types that impact the tumor response to conventional treatments. However, even in this poorly responsive tumor the extent of T cell infiltration as determined by quantitative immunohistology is a candidate prognostic factor for patient outcome. As such, even more comprehensive immunophenotyping of the tumor environment, such as immune cell type deconvolution via inference models based on gene expression profiling, holds significant promise. We hypothesized that RNA-Seq can provide a comprehensive alternative to quantitative immunohistology for immunophenotyping pancreatic cancer. We performed RNA-Seq on a prospective cohort of pancreatic tumor specimens and compared multiple approaches for gene expression-based immunophenotyping analysis compared to quantitative immunohistology. Our analyses demonstrated that while gene expression analyses provide additional information on the complexity of the tumor immune environment, they are limited in sensitivity by the low overall immune infiltrate in pancreatic cancer. As an alternative approach, we identified a set of genes that were enriched in highly T cell infiltrated pancreatic tumors, and demonstrate that these can identify patients with improved outcome in a reference population. These data demonstrate that the poor immune infiltrate in pancreatic cancer can present problems for analyses that use gene expression-based tools; however, there remains enormous potential in using these approaches to understand the relationships between diverse patterns of infiltrating cells and their impact on patient treatment outcomes