Biological Inventory of Anchialine Pool Invertebrates at Pu‘uhonua o Hōnaunau National Historical Park and Pu‘ukoholā Heiau National Historic Site, Hawai‘i Island

Reports were scanned in black and white at a resolution of 600 dots per inch and were converted to text using Adobe Paper Capture Plug-in.Inventories for major groups of invertebrates were completed at anchialine pool complexes in Pu‘uhonua o Hōnaunau National Historical Park (PUHO) and Pu‘ukoholā Heiau National Historic Site (PUHE) on the island of Hawai‘i. Nine pools within two pool complexes were surveyed at PUHO, along with one extensive pool at the terminus of Makeāhua Gulch at PUHE. At both parks, inventories documented previously unreported diversity, with pool complexes at PUHO exhibiting greater species richness for most taxa than the pool at PUHE. Inventories at PUHO recorded five species of molluscs, four species of crustaceans (including the candidate endangered shrimp Metabetaeus lohena), two species of Orthoptera, four species of Odonata (including the candidate endangered damselfly Megalagrion xanthomelas), fourteen species of Diptera, nine taxa of plankton, and thirteen species of ants; inventories at the PUHE pool produced only one species of mollusc, two species of crustacean, at least one species of Orthoptera, four species of Odonata, thirty species of Diptera, five taxa of plankton, and four species of ants. Further survey work may be necessary to document the full diversity of pool fauna, especially in species-rich groups like the Diptera. Inventory data will be used to generate a network wide database of species presence and distribution, and will aid in developing management plans for anchialine pool resources.This inventory was made possible thanks to support from the National Park Service Inventory and Monitoring Program and the U.S. Geological Survey Pacific Island Ecosystems Research Center

Blood and tissue biomarker analysis in dogs with osteosarcoma treated with palliative radiation and intra-tumoral autologous natural killer cell transfer.

We have previously reported radiation-induced sensitization of canine osteosarcoma (OSA) to natural killer (NK) therapy, including results from a first-in-dog clinical trial. Here, we report correlative analyses of blood and tissue specimens for signals of immune activation in trial subjects. Among 10 dogs treated with palliative radiotherapy (RT) and intra-tumoral adoptive NK transfer, we performed ELISA on serum cytokines, flow cytometry for immune phenotype of PBMCs, and PCR on tumor tissue for immune-related gene expression. We then queried The Cancer Genome Atlas (TCGA) to evaluate the association of cytotoxic/immune-related gene expression with human sarcoma survival. Updated survival analysis revealed five 6-month survivors, including one dog who lived 17.9 months. Using feeder line co-culture for NK expansion, we observed maximal activation of dog NK cells on day 17-19 post isolation with near 100% expression of granzyme B and NKp46 and high cytotoxic function in the injected NK product. Among dogs on trial, we observed a trend for higher baseline serum IL-6 to predict worse lung metastasis-free and overall survival (P = 0.08). PCR analysis revealed low absolute gene expression of CD3, CD8, and NKG2D in untreated OSA. Among treated dogs, there was marked heterogeneity in the expression of immune-related genes pre- and post-treatment, but increases in CD3 and CD8 gene expression were higher among dogs that lived > 6 months compared to those who did not. Analysis of the TCGA confirmed significant differences in survival among human sarcoma patients with high and low expression of genes associated with greater immune activation and cytotoxicity (CD3e, CD8a, IFN-γ, perforin, and CD122/IL-2 receptor beta). Updated results from a first-in-dog clinical trial of palliative RT and autologous NK cell immunotherapy for OSA illustrate the translational relevance of companion dogs for novel cancer therapies. Similar to human studies, analyses of immune markers from canine serum, PBMCs, and tumor tissue are feasible and provide insight into potential biomarkers of response and resistance

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Corruption Intentions Among Prospective Elites in Ghana: An Economy of Esteem

Besides its multiple harms, corruption undermines the rule of law and impedes the effective functioning of criminal justice institutions. It involves both elites in bending rules and laws as well as police at the bottom of the hierarchy asking for bribes. We analyze corruption intentions within the framework of Brennan and Pettit’s “economy of esteem,” using three main conceptual frameworks: attachment to kinship groups, materialistic orientations, and deterrence. We draw on data from a survey of 530 university students in Ghana to examine predictors of corruption intentions of prospective elites. Our prospective elites were more inclined to resort to influence peddling rather than to pay bribes directly. We find that attitudinal patterns indicative of esteem predict intentions to engage in corrupt exchanges across different agencies and contexts—police, procurement for government, and abuse of power—as well as different types of action, whether bribe payment or nepotism. In contrast, citizenly pride (and self-esteem) motivates integrity across all types of corrupt exchange. Deterrence, in terms of certainty, had a more consistently negative impact on intentions to engage in nepotism than in bribe paying and acceptance, with public procurement being the exception; no effect was found for stigma, and only police nepotism was an exception to the otherwise non-significant effects of severity. </jats:p

Blood and tissue biomarker analysis in dogs with osteosarcoma treated with palliative radiation and intra-tumoral autologous natural killer cell transfer.

We have previously reported radiation-induced sensitization of canine osteosarcoma (OSA) to natural killer (NK) therapy, including results from a first-in-dog clinical trial. Here, we report correlative analyses of blood and tissue specimens for signals of immune activation in trial subjects. Among 10 dogs treated with palliative radiotherapy (RT) and intra-tumoral adoptive NK transfer, we performed ELISA on serum cytokines, flow cytometry for immune phenotype of PBMCs, and PCR on tumor tissue for immune-related gene expression. We then queried The Cancer Genome Atlas (TCGA) to evaluate the association of cytotoxic/immune-related gene expression with human sarcoma survival. Updated survival analysis revealed five 6-month survivors, including one dog who lived 17.9 months. Using feeder line co-culture for NK expansion, we observed maximal activation of dog NK cells on day 17-19 post isolation with near 100% expression of granzyme B and NKp46 and high cytotoxic function in the injected NK product. Among dogs on trial, we observed a trend for higher baseline serum IL-6 to predict worse lung metastasis-free and overall survival (P = 0.08). PCR analysis revealed low absolute gene expression of CD3, CD8, and NKG2D in untreated OSA. Among treated dogs, there was marked heterogeneity in the expression of immune-related genes pre- and post-treatment, but increases in CD3 and CD8 gene expression were higher among dogs that lived > 6 months compared to those who did not. Analysis of the TCGA confirmed significant differences in survival among human sarcoma patients with high and low expression of genes associated with greater immune activation and cytotoxicity (CD3e, CD8a, IFN-γ, perforin, and CD122/IL-2 receptor beta). Updated results from a first-in-dog clinical trial of palliative RT and autologous NK cell immunotherapy for OSA illustrate the translational relevance of companion dogs for novel cancer therapies. Similar to human studies, analyses of immune markers from canine serum, PBMCs, and tumor tissue are feasible and provide insight into potential biomarkers of response and resistance

A brain precursor atlas reveals the acquisition of developmental-like states in adult cerebral tumours.

Human cerebral cancers are known to contain cell types resembling the varying stages of neural development. However, the basis of this association remains unclear. Here, we map the development of mouse cerebrum across the developmental time-course, from embryonic day 12.5 to postnatal day 365, performing single-cell transcriptomics on >100,000 cells. By comparing this reference atlas to single-cell data from >100 glial tumours of the adult and paediatric human cerebrum, we find that tumour cells have an expression signature that overlaps with temporally restricted, embryonic radial glial precursors (RGPs) and their immediate sublineages. Further, we demonstrate that prenatal transformation of RGPs in a genetic mouse model gives rise to adult cerebral tumours that show an embryonic/juvenile RGP identity. Together, these findings implicate the acquisition of embryonic-like states in the genesis of adult glioma, providing insight into the origins of human glioma, and identifying specific developmental cell types for therapeutic targeting