The Impact of Trauma on Young Children/The Effect of Animal-Assisted Intervention on Young Children with Trauma

The purpose of this study is to determine the impact of trauma on the development of young children. This study will define trauma and its symptoms, determine the effect of trauma on the brain and critical development, and identify strategies and interventions. The purpose of this study is to identify the effects of Animal-Assisted Intervention (AAI) on young children with trauma. This study will define AAI and determine if animals are an appropriate therapy for young children

Heroin versus cocaine: opposite choice as a function of context but not of drug history in the rat

Rationale Previous studies have shown that rats trained to self-administer heroin and cocaine exhibit opposite preferences, as a function of setting, when tested in a choice paradigm. Rats tested at home prefer heroin to cocaine whereas rats tested outside the home prefer cocaine to heroin. Here we investigated whether drug history would influence subsequent drug preference in distinct settings. Based on a theoretical model of drug-setting interaction, we predicted that regardless of drug history rats would prefer heroin at home and cocaine outside the home. Methods Rats with double-lumen catheters were first trained to self-administer either heroin (25 μg/kg) or cocaine (400 μg/kg) for 12 consecutive sessions. Twenty-six rats were housed in the self-administration chambers (thus, they were tested at home) whereas 30 rats lived in distinct home cages and were transferred to self-administration chambers only for the self-administration session (thus, they were tested outside the home). The rats were then allowed to choose repeatedly between heroin and cocaine within the same session for 7 sessions. Results Regardless of the training drug, the rats tested outside the home preferred cocaine to heroin whereas the rats tested at home preferred heroin to cocaine. There was no correlation between drug preference and drug intake during the training phase. Conclusion Drug preferences were powerfully influenced by the setting but, quite surprisingly, not by drug history. This suggests that, under certain conditions, associative learning processes and drug-induced neuroplastic adaptations play a minor role in shaping individual preferences for one drug or the other

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Anthraquinone-based bird repellent for sunflower crops

Non-lethal alternatives are needed to manage bird damage to confectionery and oilseed sunflower crops (Helianthus annuus). Ring-necked pheasants (Phasianus colchicus) can cause localized damage to newly planted sunflower, and blackbirds (Icterids) damage ripening sunflower annually in the United States of America. We conducted seed germination experiments, a repellent efficacy study with ring-necked pheasants and Avipel® repellent (a.i. 50% 9, 10-anthraquinone), and laboratory and field efficacy studies with common grackles (Quiscalus quiscula) and Avipel®-treated confectionery sunflower. Compared to the germination of seeds not treated with anthraquinone, we observed no negative effects of up to 12,223 ppm, 14,104 ppm, and 11,569ppm anthraquinone seed treatments for germination of confectionery sunflower, oilseed sunflower, and canola seeds, respectively. Pheasants avoided emergent sunflower seedlings (12 days post-planting) from 15,800ppm anthraquinone seed treatments during a caged preference test (P = 0.045). We observed a positive concentration–response relationship (P = 0.001) and predicted a threshold concentration (i.e., 80% repellency) of 9200ppm anthraquinone for common grackles offered Avipel®-treated confectionery sunflower seeds. Grackles also reliably discriminated between untreated sunflower and seeds treated with 1300ppm anthraquinone in captivity (P \u3c 0.001). During our field efficacy study for ripening confectionery sunflower, we observed 18% damage among anthraquinone-treated enclosures and 64% damage among untreated enclosures populated with common grackles (P \u3c 0.001). Harvested seed mass averaged 2.54 kg (dry weight) among treated enclosures and 1.24 kg among untreated enclosures (P \u3c 0.001). Our laboratory and field efficacy data provide a reliable basis for planning future field applications of anthraquinone-based repellents for protection of sunflower crops. Supplemental field efficacy studies are necessary for development of an effective avian repellent and management of avian depredation of ripening agricultural crops, including oilseed sunflower

Laboratory efficacy of an anthraquinone-based repellent for reducing bird damage to ripening corn

Wildlife repellents provide a non-lethal alternative for managing agricultural impacts associated with wildlife depredation. To evaluate a potential bird repellent for ripening corn, we conducted a feeding experiment at the United States Department of Agriculture, National Wildlife Research Center with 66 red-winged blackbirds (Agelaius phoeniceus). Using a two-choice experimental design we tested the efficacy of Avipel repellent (a.i. 50% 9,10-anthraquinone) on ripening sweet corn. Red-winged blackbirds consumed an average of 8.6% ± 0.9% of kernels from untreated ears and 5.3% ± 1.1% from ears treated with anthraquinone. The interaction between anthraquinone concentration and corn treatment suggests a positive concentration-response for red-winged blackbirds. Odds ratio analysis suggests red-winged blackbirds were 1.4 times more likely to damage untreated sweet corn compared to treated sweet corn. These results suggest efficacy of anthraquinone-based products as red-wing blackbird repellents for ripening corn. Moreover, exposure to anthraquinone-based repellents may reduce consumption of a food matrix that receives little to no direct anthraquinone exposure. Supplemental research is recommended to evaluate anthraquinone-based repellents under field conditions, including the establishment of a chemical tolerance for food and feed use

Therapeutic potential of macrophage colony-stimulating factor (CSF1) in chronic liver disease.

Resident and recruited macrophages control the development and proliferation of the liver. We showed previously in multiple species that treatment with a macrophage colony stimulating factor (CSF1)-Fc fusion protein initiated hepatocyte proliferation and promoted repair in models of acute hepatic injury in mice. Here we investigated the impact of CSF1-Fc on resolution of advanced fibrosis and liver regeneration, utilizing a non-resolving toxin-induced model of chronic liver injury and fibrosis in C57BL/6J mice. Co-administration of CSF1-Fc with exposure to thioacetamide (TAA) exacerbated inflammation consistent with monocyte contributions to initiation of pathology. After removal of TAA, either acute or chronic CSF1-Fc treatment promoted liver growth, prevented progression and promoted resolution of fibrosis. Acute CSF1-Fc treatment was also anti-fibrotic and pro-regenerative in a model of partial hepatectomy in mice with established fibrosis. The beneficial impacts of CSF1-Fc treatment were associated with monocyte-macrophage recruitment and increased expression of remodeling enzymes and growth factors. These studies indicate that CSF1-dependent macrophages contribute to both initiation and resolution of fibrotic injury and that CSF1-Fc has therapeutic potential in human liver disease

Appendix D. Stable isotope ratios (13C/12C) of carbon (δ13C) for fish and local food sources (benthic invertebrates and periphyton) collected from multiple locations in rivers that vary in rhythmicity.

Stable isotope ratios (13C/12C) of carbon (δ13C) for fish and local food sources (benthic invertebrates and periphyton) collected from multiple locations in rivers that vary in rhythmicity

Appendix C. Seasonality index, interannual variation in maximum flood peak, and mean and maximum annual runoff for gauges used in the study.

Seasonality index, interannual variation in maximum flood peak, and mean and maximum annual runoff for gauges used in the study