CERKL is upregulated in cutaneous squamous cell carcinoma and maintains cellular sphingolipids and resistance to oxidative stress.

BACKGROUND: Ceramide kinase-like protein (CERKL) was originally described in retinal tissue. CERKL has been shown to protect cells from oxidative stress, and mutations in CERKL underlie the inherited disease retinitis pigmentosa. CERKL expression maintains cellular sphingolipids via an unknown mechanism. OBJECTIVES: To determine whether CERKL is expressed in epidermis and cutaneous squamous cell carcinoma (cSCC) and whether CERKL expression affects cSCC sphingolipid metabolism and susceptibility to oxidative stress. METHODS: CERKL expression was determined by RNA-Seq, quantitative polymerase chain reaction and immunohistochemistry. CERKL was knocked down in cSCC cells using small interfering RNA. Sphingolipid content was analysed by liquid chromatography-mass spectrometry. Oxidative stress was induced by treatment with H2 O2 , and apoptosis was measured using flow cytometry to determine annexin V binding. RESULTS: CERKL mRNA and protein are highly expressed in actinic keratosis and cSCC in comparison with normal epidermis. CERKL is also expressed in metabolically active epithelial cells in normal hair bulbs and sebaceous glands. CERKL knockdown in cultured cSCC cells reduces cellular sphingolipid content and enhances susceptibility to oxidative stress. CONCLUSIONS: These findings suggest that CERKL may be important in cSCC progression and could lead to novel strategies for prevention and treatment of cSCC.

CERKL is Upregulated in Cutaneous Squamous Cell Carcinoma and Maintains Cellular Sphingolipids and Resistance to Oxidative Stress.

BACKGROUND: Ceramide Kinase-Like Protein (CERKL) was originally described in retinal tissue. CERKL has been shown to protect cells from oxidative stress, and mutations in CERKL underlie the inherited disease, retinitis pigmentosa. CERKL expression maintains cellular sphingolipids via an unknown mechanism. OBJECTIVES: To determine whether CERKL is expressed in epidermis and cutaneous squamous cell carcinoma (cSCC) and whether CERKL expression affects cSCC sphingolipid metabolism and susceptibility to oxidative stress. METHODS: CERKL expression was determined by RNA-Seq, qPCR and immunohistochemistry. CERKL was knocked down in cSCC cells using siRNA. Sphingolipid content was analyzed by liquid chromatography-mass spectrometry (LC-MS). Oxidative stress was induced by treatment with H2 O2 , and apoptosis was measured using flow cytometry to determine annexin v binding. RESULTS: CERKL mRNA and protein are highly expressed in actinic keratosis and cSCC in comparison with normal epidermis. CERKL also is expressed in metabolically active epithelial cells in normal hair bulbs and sebaceous glands. CERKL knockdown in cultured cSCC cells reduces cellular sphingolipid content and enhances susceptibility to oxidative stress. CONCLUSIONS: These findings suggest that CERKL may be important in cSCC progression and could lead to novel strategies for prevention and treatment of cSCC.

Characterization of regional transport and dispersion using Project MOHAVE tracer data.

Perfluorocarbon tracers were released continuously from several surface locations and one power plant stack location during the winter (30 days) and summer (50 days) intensive studies as part of Project MOHAVE. Tracers were released in winter from the Mohave Power Plant (MPP) and Dangling Rope, UT, located on the shore of Lake Powell near Page, AZ; and in summer from MPP, the Tehachapi Pass between the Mojave Desert and the Central Valley in California, and El Centro, CA, on the California-Mexico border. At the Tehachapi tracer release site six-hour pulses of a separately identifiable perfluorocarbon tracer were released every four days in order to assess the time for the tracer to clear the monitoring network. Daily 24-hr integrated samples were collected at about 30 sites in four states. Limited tracer concentration data with higher time resolution is also available. Graphical displays and analyses identify several regional transport paths, including a convergence zone in the Mojave Desert, the importance of terrain channeling, especially in winter, and a relationship between 24-hr maximum influence function and distance that may prove useful as a scoping tool and to test regional scale air quality models. In winter, Dangling Rope tracer was routinely transported through the entire length of the Grand Canyon, while in summer, MPP tracer was routinely transported over most of Lake Mead.

Tracking Regional Background in a Haze Attribution Experiment.

Emissions from distant source areas are often imagined to provide a steady background to the emissions of whatever local sources are being studied. As part of Project MOHAVE in summer 1992, several air mass markers and an injected stack tracer were measured hourly near the Grand Canyon. Observed haze events generally coincided with transients in methylchloroform and water vapor, which we interpret as endemic tags for air from southern California and the subtropics. The results depict a dynamic regional background.

Preliminary on-road measurement of the effect of oxygenated fuel on CO emissions near Las Vegas, Nevada.

A preliminary measurement of an oxygenated fuel effect for in-use vehicles travelling at freeway speed was conducted near Las Vegas, NV, in January 1991 and May 1992. The experimental design was based on two principal factors: (1) the large volume of traffic that visits Las Vegas from Southern California on three-day holiday weekends and (2) the fact that, at the time of the study, the Las Vegas area used oxygenated fuels in the winter and Southern California did not. Measurements were conducted at carefully selected sites 20 km southwest of Las Vegas near Sloan, NV, and were accomplished with the Fuel Efficiency Automoblie Test (FEAT) remote sensor developed at the University of Denver. The January 1991 measurements were made during the Las Vegas oxyfuel season, while the May 1992 control measurements were made outside the oxyfuel season. Over 24,500 individual CO concentrations were measured; registration data from over 5,500 of these vehicles were obtained from the license plate numbers. After corrections for differences in velocity and mean age, the Las Vegas outbound (oxyfuel) CO emissions on Monday morning of the January holiday weekend showed a difference of -18% +/- 11% compared to the inbound (non-oxyfuel) CO emissions on Friday evening preceding the holiday weekend.

The effect of solubility and hyperlipidemia on perioperative arterial blood gas tensions.

A case is presented to illustrate the need for technical care when handling blood gas samples. The physics of solubility are used to show hour samples changed their oxygen tension (pO2) during handling, while investigating a clinical case to show the effect of hyperlipidemia on blood gases. It appeared that inadvertent access to air allowed atmospheric oxygen to equilibrate with the sample. The physical laws predicting the effect of partial pressure and temperature on gas solubility in a liquid are illustrated by the pO2 levels measured in this case. Effects due to hyperlipidemia were not observed. The calculations are described in detail. Brief suggestions for sample handling to avoid misleading results from such cases are discussed.

Patient awareness during general anesthesia: a shocking outcome.

Patient awareness under minimal anesthesia may include the painful impulses of a nerve stimulator used for the monitoring of muscle relaxation. We present a case where discomfort from nerve stimulation was greater than that caused by the surgical incision or the endotracheal tube.

Identification of Candidate Clean Air Corridors for the Colorado Plateau.

The U.S. Clean Air Act, amended in 1990, mandated the establishment of the Grand Canyon Visibility Transport Commission (GCVTC). The commission is required to submit a report to the U.S. Environmental Protection Agency addressing visibility issues in the region, including "the establishment of clean air corridors, in which additional restrictions on increases in emissions may be appropriate to protect visibility in affected Class I areas." This paper presents a methodology to identify candidate geographic areas for consideration for Clean Air Corridor (CAC) status for Colorado Plateau Class I areas. The methodology uses thousands of model determined trajectories over a five year period (1988 to 1992) to indicate the paths taken by air that arrives during clean air conditions at Class I areas. These clean air back-trajectories identify upwind areas where pollution emissions could jeopardize currently pristine visibility. Using this methodology, six candidate areas are identified, ranging in size from 75,000 to 506,000 square miles, and permitting varying levels of visibility protection for clean air days at Grand Canyon, Canyonlands, and Petrified Forest National Parks. Assuming effective emissions management of the CAC, the larger the CAC, the greater the visibility protection during clean air conditions.