Geochemistry of Ground Water - Surface Water Interactions and Metals Loading Rates in the North Fork of the American Fork River, Utah, from an Abandoned Silver/Lead Mine

The aqueous geochemistry and hydrology of the North Fork of the American Fork River, its tributaries, and the ground water in the vicinity of the Pacific Mine site were investigated in order to determine what impact ground water entering the North Fork has on toxic metal loads in the river. Toxic metal contamination in the North Fork is great enough that brown and cutthroat trout have absorbed lead, cadmium, and arsenic in their tissues at concentrations that are hazardous to human health if consumed. Ground water that flows through the mine site flows directly through the mine tailings before entering the North Fork, which produces an acidic ground water plume that has high concentrations of toxic metals. Together, the surface water discharge results and toxic metals concentrations from the surface and ground waters were used to determine toxic metals loading rates in the North Fork and its tributaries. The results suggest that the dissolved toxic metals (As, Cd, Cu, Fe, Mn, Pb, and Zn) enter the North Fork when the river is gaining water from the ground water. However, the total toxic metal load generally decreases through the reach of river adjacent to the mine site and is significantly greater than the dissolved load. Cadmium and Mn travel as dissolved species while Cu, Fe, Pb, and Zn travel as suspended solids in the North Fork and its tributaries. Arsenic seems to be associated with both the suspended solids and travel in the dissolved state. The geochemical modeling program PHREEQC and the diffuse double layer surface complexation model were used to investigate the chemistry that controls toxic metal mobility and attenuation in the surface and ground waters at the mine site. Based on PHREEQC results, the most important reaction in these waters is the precipitation of hydrous fe1Tic oxide. The toxic metals that sorb to the hydrous ferric oxide are Cu, Pb, most importantly Zn, and to a lesser degree As

The metastasis-promoting roles of tumor-associated immune cells

Tumor metastasis is driven not only by the accumulation of intrinsic alterations in malignant cells, but also by the interactions of cancer cells with various stromal cell components of the tumor microenvironment. In particular, inflammation and infiltration of the tumor tissue by host immune cells, such as tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells have been shown to support tumor growth in addition to invasion and metastasis. Each step of tumor development, from initiation through metastatic spread, is promoted by communication between tumor and immune cells via the secretion of cytokines, growth factors and proteases that remodel the tumor microenvironment. Invasion and metastasis requires neovascularization, breakdown of the basement membrane, and remodeling of the extracellular matrix for tumor cell invasion and extravasation into the blood and lymphatic vessels. The subsequent dissemination of tumor cells to distant organ sites necessitates a treacherous journey through the vasculature, which is fostered by close association with platelets and macrophages. Additionally, the establishment of the pre-metastatic niche and specific metastasis organ tropism is fostered by neutrophils and bone marrow-derived hematopoietic immune progenitor cells and other inflammatory cytokines derived from tumor and immune cells, which alter the local environment of the tissue to promote adhesion of circulating tumor cells. This review focuses on the interactions between tumor cells and immune cells recruited to the tumor microenvironment, and examines the factors allowing these cells to promote each stage of metastasis

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10-10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10-10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis