Notch/Delta signaling constrains reengineering of pro-T cells by PU.1

PU.1 is essential for early stages of mouse T cell development but antagonizes it if expressed constitutively. Two separable mechanisms are involved: attenuation and diversion. Dysregulated PU.1 expression inhibits pro-T cell survival, proliferation, and passage through β-selection by blocking essential T cell transcription factors, signaling molecules, and Rag gene expression, which expression of a rearranged T cell antigen receptor transgene cannot rescue. However, Bcl2 transgenic cells are protected from this attenuation and may even undergo β-selection, as shown by PU.1 transduction of defined subsets of Bcl2 transgenic fetal thymocytes with differentiation in OP9-DL1 and OP9 control cultures. The outcome of PU.1 expression in these cells depends on Notch/Delta signaling. PU.1 can efficiently divert thymocytes toward a myeloid-like state with multigene regulatory changes, but Notch/Delta signaling vetoes diversion. Gene expression analysis distinguishes sets of critical T lineage regulatory genes with different combinatorial responses to PU.1 and Notch/Delta signals, suggesting particular importance for inhibition of E proteins, Myb, and/or Gfi1 (growth factor independence 1) in diversion. However, Notch signaling only protects against diversion of cells that have undergone T lineage specification after Thy-1 and CD25 up-regulation. The results imply that in T cell precursors, Notch/Delta signaling normally acts to modulate and channel PU.1 transcriptional activities during the stages from T lineage specification until commitment

Barriers to self-monitoring of blood glucose among adults with diabetes in an HMO: A cross sectional study

BACKGROUND: Recent studies suggest that patients at greatest risk for diabetes complications are least likely to self-monitor blood glucose. However, these studies rely on self-reports of monitoring, an unreliable measure of actual behavior. The purpose of the current study was to examine the relationship between patient characteristics and self-monitoring in a large health maintenance organization (HMO) using test strips as objective measures of self-monitoring practice. METHODS: This cross-sectional study included 4,565 continuously enrolled adult managed care patients in eastern Massachusetts with diabetes. Any self-monitoring was defined as filling at least one prescription for self-monitoring test strips during the study period (10/1/92–9/30/93). Regular SMBG among test strip users was defined as testing an average of once per day for those using insulin and every other day for those using oral sulfonylureas only. Measures of health status, demographic data, and neighborhood socioeconomic status were obtained from automated medical records and 1990 census tract data. RESULTS: In multivariate analyses, lower neighborhood socioeconomic status, older age, fewer HbA1c tests, and fewer physician visits were associated with lower rates of self-monitoring. Obesity and fewer comorbidities were also associated with lower rates of self-monitoring among insulin-managed patients, while black race and high glycemic level (HbA1c>10) were associated with less frequent monitoring. For patients taking oral sulfonylureas, higher dose of diabetes medications was associated with initiation of self-monitoring and HbA1c lab testing was associated with more frequent testing. CONCLUSIONS: Managed care organizations may face the greatest challenges in changing the self-monitoring behavior of patients at greatest risk for poor health outcomes (i.e., the elderly, minorities, and people living in low socioeconomic status neighborhoods)

Interactive influences of ozone and climate on streamflow of forested watersheds

The capacity of forests to mitigate global climate change can be negatively influenced by tropospheric ozone that impairs both photosynthesis and stomatal control of plant transpiration, thus affecting ecosystem productivity and watershed hydrology. We have evaluated individual and interactive effects of ozone and climate on late season streamflow for six forested watersheds (38–970 000 ha) located in the Southeastern United States. Models were based on 18–26 year data records for each watershed and involved multivariate analysis of interannual variability of late season streamflow in response to physical and chemical climate during the growing season. In all cases, some combination of ozone variables significantly improved model performance over climate-only models. Effects of ozone and ozone × climate interactions were also consistently negative and were proportional to variations in actual ozone exposures, both spatially across the region and over time. Conservative estimates of the influence of ozone on the variability (R2) of observed flow ranged from 7% in the area of lowest ozone exposure in West Virginia to 23%in the areas of highest exposure in Tennessee. Our results are supported by a controlled field study using free-air concentration enrichment methodology which indicated progressive ozone-induced loss of stomatal control over tree transpiration during the summer in mixed aspen-birch stands. Despite the frequent assumption that ozone reduces tree water loss, our findings support increasing evidence that ozone at near ambient concentrations can reduce stomatal control of leaf transpiration, and increase water use. Increases in evapotranspiration and associated streamflow reductions in response to ambient ozone exposures are expected to episodically increase the frequency and severity of drought and affect flow-dependent aquatic biota in forested watersheds. Regional and global models of hydrologic cycles and related ecosystem functions should consider potential interactions of ozone with climate under both current and future warmer and ozone-enriched climatic conditions

Effects of Oil Shale Leachate on Phytoplankton Productivity

The effects of oil shale leachate and salinity additions on the productivity of freshwater algae were studied in the laboratory using batch bioassays. These batch bioassays were used to screen variations of ten salts in single and multiple additions of all possible combinations of the ten salts; water extractions of different processed and unprocessed oil shales; and the concentration effects of both the salts from 0.3 N to 0.05 N as NaCl and the oil shale extractions on the growth of standard test algae and indigenous algae from Lake Powell. The batch bottle bioassays were conducted following the standard algal assay procedure as closely as possible. Variations in the standard algal assay procedure included media variation with the use of indigenous algal species isolated from Lake Powell and the use of three different algal species isolated from Lake Powell and the use of three different algal species for test innoculum in the bioassay procedure. The biomass was monitored using optical density, chlorophyll a fluorescence, and/or cell counts. The indegenous algal species were found to be negatively affected but more tolerant to all salinity additions than the standard test alga. The growth of the indigenous algal species

Utah Surface Impoundment Assessment Report

Executive Summary: The Surface Impoundment Assessment process presented an organized consistent systme for evaluating potential threats to groundwater resources from surface impoundments of wastes. This assessment established a data base which locates wastes surface impoundments in Utah and assesses the majority of these impoundments with this prescribed system (Appendix F). This data base may be used to identify surface impoundments in Utah which may create problems with regard to groundwater contamination. Data Summary: The potential hazards of the surface impoundments assessed to groundwater is based on two values established during the assessment procedure. These values are identified as the pollution potential and the health hazard of the sruface impoundment. The pollution potential rating is based on the first four steps of the assessment procedure. out of the 711 impoundments assessed during this study 154 impoundments, of 22 percent of these impoundment, exhibited a pollution potential value high enough to be of concern (greater than 19 assessment units). The health hazard ratin gis based on the proximity of an impoundment to a water well and the anticipated direction of movement of the waste plume. Out of the 154 impoundments exhibility high pollution potentials, 35 impoundments, or 23 percent of these impoundments, also exhibilited a health hazard rating which may be cause for concern (Case A). These 35 impoundments exhibility a combination of a high pollution potential and health hazard values are located on 13 sites. They represent sites from every category studied. These sites may pose a threat to groundwater supplies as identified by the assessment process. The assessment data are discussed in more detail in Chapter 4. There have been instances of groundwater contamination in Utah. On e of these instances has been documented through legal action. These instances are discussed in Chapter 6. State Program for Protecting Groundwater: The Utah State Board of Health is a body politic recommended by the Governor and approved by the Utah Senate that serves as the regulatory authority for the State Department of Health (Holt, 1979). Regulatory and enforcement authroity is vested in the State Board of Health by Section 26-15-5 of the Utah Cose Annotated, 1953, as amended. Additional regulatory committees have been authorized by state law to promulgate rules for the control of specific health or environmental programs as have been deemed necessary with increasing demands on the state\u27s natural resources and environmental protection programs. The state water pollution control organziation consists of the Dibision of Environmental Health within the State Health Department (Pitkin, 1979). The Division of Environmental Health includes Bureaus of Water Pollution Control, Public Water Supply, and Solid Waste Management, each working under separate state legislative authority and under separate federal acts: The Federal Clean Water Act, and Safe Drinking Water Act, and the Resource Conservation and Recovery Act. The organization of the state environment health programs is currently under review by a state appointed reorganization committee. Therefore, this organication may change within the near future (Dalley, 1980). Under present State Health Department policy, the Bureau of Water Pollution Control has been designated as the lead agency for conductin gthe permitting and operational requirements for pits, ponds and lagoons and for the construction of facilities for the containment of sludges from water and sewage treatment plants (Holt, 1979). It should be understood, howeber, that a dual regulatory responsibility exists between the Bureaus of Water Pollution Control and Solid Waste Mangement for control and disposal of sewage and wastewater sludges. The Bureau of Solid Waste Management presently assumes a significant role in establishing policy for the management of sewage and water treatment sludge. Conclusions and Recommendations: At the present time, no specific groundwater program exists in the State Division of Health. Therefore, responsibility for the protection of groundwater is also shared by the state agencies mentioned above. A staff would be necessary to achieve protection of drinking water supplies by addressing specific needs within this state. One area requiring attention is enforcement of existing laws. In order to adequately enforce these laws there is a need for increased public education and manpower within the state (Georgeson, 1979a; Gray 1979; Pitkin, 1979a; Thompson, 1979). The enforcement interpretation of these laws must allow enough flexibility to prevent illegal actions. For example, the closure of a small dump may promote illegal actions. For example, the closure of a small dump may promote illegal dumping (Gray, 1979). Enforcement capabilities require an adequate data base, monitoring program, and staff expertise. Inadequacies exist in baseline groundwater quality data (Pitkin, 1979a) and hydrogeology data (Georgeson, 1979a) especially in remote areas of the state. Also, more quality data are needed on the wastes being treated (Maxwell, 1979). Increased monitoring is necessary to create an adequate data base and to identify problems before public complaints call attention to them

Full hydrodynamic reversibility of the weak dimerization of vancomycin and elucidation of its interaction with VanS monomers at clinical concentration

© 2017 The Author(s). The reversibility and strength of the previously established dimerization of the important glycopeptide antibiotic vancomycin in four different aqueous solvents (including a medically-used formulation) have been studied using short-column sedimentation equilibrium in the analytical ultracentrifuge and model-independent SEDFIT-MST analysis across a range of loading concentrations. The change in the weight average molar mass M w with loading concentration was consistent with a monomer-dimer equilibrium. Overlap of data sets of point weight average molar masses M w(r) versus local concentration c(r) for different loading concentrations demonstrated a completely reversible equilibrium process. At the clinical infusion concentration of 5 mg.mL-1 all glycopeptide is dimerized whilst at 19 μg.mL-1 (a clinical target trough serum concentration), vancomycin was mainly monomeric

The proteome of cholesteryl-ester-enriched versus triacylglycerol-enriched lipid droplets

Within cells, lipids are stored in the form of lipid droplets (LDs), consisting of a neutral lipid core, surrounded by a phospholipid monolayer and an outer layer of protein. LDs typically accumulate either triacylglycerol (TAG) and diacylglycerol or cholesteryl ester (CE), depending on the type of tissue. Recently, there has been an increased interest in the proteins that surround LDs. LD proteins have been found to be quite diverse, from structural proteins to metabolic enzymes, proteins involved in vesicular transport, and proteins that may play a role in LD formation. Previous proteomics analyses have focused on TAG-enriched LDs, whereas CE-enriched LDs have been largely ignored. Our study has compared the LD proteins from CE-enriched LDs to TAG-enriched LDs in steroidogenic cells. In primary rat granulosa cells loaded with either HDL to produce CE-enriched LDs or fatty acids to produce TAG-enriched LDs, 61 proteins were found to be elevated in CE-enriched LDs and 40 proteins elevated in TAG-enriched LDs with 278 proteins in similar amounts. Protein expression was further validated by selected reaction monitoring (SRM) mass spectrometry (MS). SRM verified expression of 25 of 27 peptides that were previously detected by tandem mass tagging MS. Several proteins were confirmed to be elevated in CE-enriched LDs by SRM including the intermediate filament vimentin. This study is the first to compare the proteins found on CE-enriched LDs with TAG-enriched LDs and constitutes the first step in creating a better understanding of the proteins found on CE-enriched LDs in steroidogenic cells

Changing forest water yields in response to climate warming: results from long-term experimental watershed sites across North America

Climate warming is projected to affect forest water yields but the effects are expected to vary. We investigated how forest type and age affect water yield resilience to climate warming. To answer this question, we examined the variability in historical water yields at long-term experimental catchments across Canada and the United States over 5-year cool and warm periods. Using the theoretical framework of the Budyko curve, we calculated the effects of climate warming on the annual partitioning of precipitation (P) into evapotranspiration (ET) and water yield. Deviation (d) was defined as a catchment’s change in actual ET divided by P [AET/P; evaporative index (EI)] coincident with a shift from a cool to a warm period – a positive d indicates an upward shift in EI and smaller than expected water yields, and a negative d indicates a downward shift in EI and larger than expected water yields. Elasticity was defined as the ratio of inter annual variation in potential ET divided by P (PET/P; dryness index) to inter annual variation in the EI – high elasticity indicates low d despite large range in drying index (i.e., resilient water yields), low elasticity indicates high d despite small range in drying index (i.e., non-resilient water yields). Although the data needed to fully evaluate ecosystems based on these metrics are limited, we were able to identify some characteristics of response among forest types. Alpine sites showed the greatest sensitivity to climate warming with any warming leading to increased water yields. Conifer forests included catchments with lowest elasticity and stable to larger water yields. Deciduous forests included catchments with intermediate elasticity and stable to smaller water yields. Mixed coniferous/deciduous forests included catchments with highest elasticity and stable water yields. Forest type appeared to influence the resilience of catchment water yields to climate warming, with conifer and deciduous catchments more susceptible to climate warming than the more diverse mixed forest catchments