Hydrogeology and Ground-Water Monitoring of Coal-Ash Disposal Sites in a Karst Terrane near Burnside, South-Central Kentucky

The effects of two coal-ash disposal facilities on ground-water quality at the John Sherman Cooper Power Plant, located in a karst region of south-central Kentucky, were evaluated using dye traces in springs. Springs were used for monitoring rather than wells, because in a karst terrane wells are unlikely to intercept individual conduits. A closed-out ash pond located over a conduit-flow system discharges to three springs in the upper Salem and Warsaw Formations along Lake Cumberland. Water discharging from these downgradient springs is similar to springs unaffected by ash-disposal facilities and is a calcium-bicarbonate type. No constituent concentrations found in this flow system exceeded maximum contaminant levels (MCL’s) or secondary maximum contaminant levels (SMCL’s) defined by the U.S. Environmental Protection Agency. An active ash pond is situated over another conduit-flow system that discharges to springs in the lower St. Louis Limestone. Water discharging from these downgradient springs is intermediate between the calciumbicarbonate type of the unaffected springs and the calcium-sulfate type of the active ash pond. No constituent concentrations found in this flow system exceeded MCL’s or SMCL’s. A third flow system associated with a coal stockpile adjacent to the plant is delineated by springs in the St. Louis Limestone and the Salem and Warsaw Formations that discharge calcium-sulfate type water. Chromium and cadmium concentrations exceeded MCL’s in at least one sample from this flow system. Iron, manganese, sulfate, and total dissolved solid concentrations exceeded SMCL’s in at least one sample. The closed-out ash pond appears to have no adverse impact on the water quality, nor does the active ash pond. In general, the coal stockpile has a more adverse impact on ground-water quality in the study area than the ash-disposal facilities

Extracellular Matrix Disparities in an \u3ci\u3eNkx2-5\u3c/i\u3e Mutant Mouse Model of Congenital Heart Disease

Congenital heart disease (CHD) affects almost one percent of all live births. Despite diagnostic and surgical reparative advances, the causes and mechanisms of CHD are still primarily unknown. The extracellular matrix plays a large role in cell communication, function, and differentiation, and therefore likely plays a role in disease development and pathophysiology. Cell adhesion and gap junction proteins, such as integrins and connexins, are also essential to cellular communication and behavior, and could interact directly (integrins) or indirectly (connexins) with the extracellular matrix. In this work, we explore disparities in the expression and spatial patterning of extracellular matrix, adhesion, and gap junction proteins between wild type and Nkx2-5+/R52G mutant mice. Decellularization and proteomic analysis, Western blotting, histology, immunostaining, and mechanical assessment of embryonic and neonatal wild type and Nkx2-5 mutant mouse hearts were performed. An increased abundance of collagen IV, fibronectin, and integrin β-1 was found in Nkx2-5 mutant neonatal mouse hearts, as well as increased expression of connexin 43 in embryonic mutant hearts. Furthermore, a ventricular noncompaction phenotype was observed in both embryonic and neonatal mutant hearts, as well as spatial disorganization of ECM proteins collagen IV and laminin in mutant hearts. Characterizing such properties in a mutant mouse model provides valuable information that can be applied to better understanding the mechanisms of congenital heart disease

H I in group interactions: HCG 44

Extending deep observations of the neutral atomic hydrogen (HI) to the environment around galaxy groups can reveal a complex history of group interactions which is invisible to studies that focus on the stellar component. Hickson Compact Group 44 (HCG 44) is a nearby example and we have combined HI data from the Karoo Array Telescope, Westerbork Synthesis Radio Telescope, and Arecibo Legacy Fast ALFA survey, in order to achieve high column density sensitivity (N_HI < 2x10^18 cm^-2) to the neutral gas over a large field-of-view beyond the compact group itself. We find the giant HI tail north of HCG 44 contains 1.1x10^9 M_Sun of gas and extends 450 kpc from the compact group: twice as much mass and 33% further than previously detected. However, the additional gas is still unable to account for the known HI deficiency of HCG 44. The tail likely formed through a strong tidal interaction and HI clouds in the tail have survived for 1 Gyr or more after being stripped. This has important implications for understanding the survival of neutral clouds in the intragroup and circumgroup medium, and we discuss their survival in the context of simulations of cold gas in hot halos. HCG 44 is one of a growing number of galaxy groups found to have more extended HI in the intragroup and circumgroup medium than previously measured. Our results provide constraints for simulations on the properties of galaxy group halos, and reveal a glimpse of what will be seen by future powerful HI telescopes and surveys.Comment: 12 pages, 6 figures. Accepted for publication in MNRA

Excess TGF-β mediates muscle weakness associated with bone metastases in mice

Cancer-associated muscle weakness is a poorly understood phenomenon, and there is no effective treatment. Here we find that seven different mouse models of human osteolytic bone metastases-representing breast, lung and prostate cancers, as well as multiple myeloma-exhibited impaired muscle function, implicating a role for the tumor-bone microenvironment in cancer-associated muscle weakness. We found that transforming growth factor (TGF)-β, released from the bone surface as a result of metastasis-induced bone destruction, upregulated NADPH oxidase 4 (Nox4), resulting in elevated oxidization of skeletal muscle proteins, including the ryanodine receptor and calcium (Ca(2+)) release channel (RyR1). The oxidized RyR1 channels leaked Ca(2+), resulting in lower intracellular signaling, which is required for proper muscle contraction. We found that inhibiting RyR1 leakage, TGF-β signaling, TGF-β release from bone or Nox4 activity improved muscle function in mice with MDA-MB-231 bone metastases. Humans with breast- or lung cancer-associated bone metastases also had oxidized skeletal muscle RyR1 that is not seen in normal muscle. Similarly, skeletal muscle weakness, increased Nox4 binding to RyR1 and oxidation of RyR1 were present in a mouse model of Camurati-Engelmann disease, a nonmalignant metabolic bone disorder associated with increased TGF-β activity. Thus, pathological TGF-β release from bone contributes to muscle weakness by decreasing Ca(2+)-induced muscle force production

Frontotemporal lobar degeneration targets brain regions linked to expression of recently evolved genes

In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of human accelerated regions (HARs), conserved sequences that have undergone positive selection during recent human evolution. To this end, we used structural neuroimaging from patients with FTLD and human brain regional transcriptomic data from controls to identify genes expressed in FTLD-targeted brain regions. We then integrated primate comparative genomic data to test our hypothesis that FTLD targets brain regions linked to expression levels of recently evolved genes. In addition, we asked whether genes whose expression correlates with FTLD atrophy are enriched for genes that undergo cryptic splicing when TDP-43 function is impaired. We found that FTLD-TDP and FTLD-tau subtypes target brain regions with overlapping and distinct gene expression correlates, highlighting many genes linked to neuromodulatory functions. FTLD atrophy-correlated genes were strongly enriched for HARs. Atrophy-correlated genes in FTLD-TDP showed greater overlap with TDP-43 cryptic splicing genes and genes with more numerous TDP-43 binding sites compared with atrophy-correlated genes in FTLD-tau. Cryptic splicing genes were enriched for HAR genes, and vice versa, but this effect was due to the confounding influence of gene length. Analyses performed at the individual-patient level revealed that the expression of HAR genes and cryptically spliced genes within putative regions of disease onset differed across FTLD-TDP subtypes. Overall, our findings suggest that FTLD targets brain regions that have undergone recent evolutionary specialization and provide intriguing potential leads regarding the transcriptomic basis for selective vulnerability in distinct FTLD molecular-anatomical subtypes

Understanding the influence of 24-hour movement behaviours on the health and development of preschool children from low-income South African settings: the SUNRISE pilot study

Background: The International Study of Movement Behaviours in the Early Years, SUNRISE, was initiated to assess the extent to which young children meet movement behaviour guidelines (physical activity, sedentary behaviour, screen time, sleep). Objective: The South African SUNRISE pilot study assessed movement behaviours in preschool children from two low-income settings, and associations between these movement behaviours, adiposity, motor skills and executive function (EF). Methods: Preschool child/parent pairs (n = 89) were recruited from preschools in urban Soweto and rural Sweetwaters. Height and weight were measured to assess adiposity. Physical activity was assessed using accelerometers while sedentary behaviour, screen time and sleep were assessed via parent report. Fine and gross motor development were measured using the Ages and Stages Questionnaire-3, and EF was assessed using the Early Years Toolbox. Results: The proportion of children meeting the physical activity guideline was 84% , 66% met the sleep guideline ,48% met the screen time guideline , and 26% met all three guidelines. Rural children were more active, but spent more time on screens compared to urban children. Most children were on track for gross (96%) and fine motor (73%) development, and mean EF scores were in the expected range for all EF measures. EF was negatively associated with screen time, and gross motor skills were positively associated with physical activity. Conclusion: The South African SUNRISE study contributes to the growing literature on 24-hour movement behaviours in SA preschool children, and highlights that these behaviours require attention in this age group