Effects of Δ⁹-tetrahydrocannabinol (THC) vapor inhalation in Sprague-Dawley and Wistar rats.

An inhalation system based on e-cigarette technology produces hypothermic and antinociceptive effects of Δ⁹-tetrahydrocannabinol (THC) in rats. Indirect comparison of some prior investigations suggested differential impact of inhaled THC between Wistar (WI) and Sprague-Dawley (SD) rats; thus, this study was conducted to directly compare the strains across inhaled and injected routes of administration. Groups (N = 8 per strain) of age-matched male SD and WI rats were prepared with radiotelemetry devices to measure temperature and then exposed to vapor from the propylene glycol (PG) vehicle or THC (25-200 mg/mL of PG) for 30 or 40 min. Additional studies evaluated effects of THC inhalation on plasma THC (50-200 mg/mL) and nociception (100-200 mg/mL) as well as the thermoregulatory effect of intraperitoneal injection of THC (5-30 mg/kg). Hypothermic effects of THC were more pronounced in SD rats, where plasma levels of THC were identical across strains, under either fixed inhalation conditions or injection of a mg/kg equivalent dose. Strain differences in hypothermia were largest after i.p. injection of THC, with SD rats exhibiting dose-dependent temperature reduction after 5 or 10 mg/kg, i.p. and the WI rats only exhibiting significant hypothermia after 20 mg/kg, i.p. The antinociceptive effects of inhaled THC (100, 200 mg/mL) did not differ significantly across the strains. These studies confirm an insensitivity of WI rats, compared with SD rats, to hypothermia induced by THC following inhalation conditions that produced identical plasma THC and antinociception. Thus, quantitative, albeit not qualitative, strain differences may be obtained when studying thermoregulatory effects of THC. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Using Satellite Imagery to Identify Tornado Damage Tracks and Recovery from the April 27, 2011 Severe Weather Outbreak

Emergency response to natural disasters requires coordination between multiple local, state, and federal agencies. Single, relatively weak tornado events may require comparatively simple response efforts; but larger "outbreak" events with multiple strong, long-track tornadoes can benefit from additional tools to help expedite these efforts. Meteorologists from NOAA's National Weather Service conduct field surveys to map tornado tracks, assess damage, and determine the tornado intensity following each event. Moderate and high resolution satellite imagery can support these surveys by providing a high-level view of the affected areas. Satellite imagery could then be used to target areas for immediate survey or to corroborate the results of the survey after it is completed. In this study, the feasibility of using satellite imagery to identify tornado damage tracks was determined by comparing the characteristics of tracks observed from low-earth orbit to tracks assessed during the official NWS storm survey process. Of the 68 NWS confirmed centerlines, 24 tracks (35.3%) could be distinguished from other surface features using satellite imagery. Within each EF category, 0% of EF-0, 3% of EF-1, 50% of EF-2, 77.7% of EF-3, 87.5% of EF-4 and 100% of EF-5 tornadoes were detected. It was shown that satellite data can be used to identify tornado damage tracks in MODIS and ASTER NDVI imagery, where damage to vegetation creates a sharp drop in values though the minimum EF-category which can be detected is dependent upon the type of sensor used and underlying vegetation. Near-real time data from moderate resolution sensors compare favorably to field surveys after the event and suggest that the data can provide some value in the assessment process

DNMT inhibitors reverse a specific signature of aberrant promoter DNA methylation and associated gene silencing in AML

<b>Background</b>. Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are neoplastic disorders of hematopoietic stem cells. DNA methyltransferase inhibitors (DNMTi), 5-azacytidine (AzaC) and 5-aza-2’-deoxycytidine (Decitabine), benefit some MDS/AML patients. However, the role of DNMTi-induced DNA hypomethylation in regulation of gene expression in AML is unclear.<p></p> <b>Results. </b> We compared the effects of AzaC on DNA methylation and gene expression using whole-genome single-nucleotide bisulfite-sequencing (WGBS) and RNA-sequencing in OCI-AML3 (AML3) cells. For data analysis, we used an approach recently developed for discovery of differential patterns of DNA methylation associated with changes in gene expression, that is tailored to single-nucleotide bisulfite-sequencing data (Washington University Interpolated Methylation Signatures (WIMSi)). By this approach, a subset of genes upregulated by AzaC was found to be characterized by AzaC-induced signature methylation loss flanking the transcription start site. These genes are enriched for genes increased in methylation and decreased in expression in AML3 cells compared to normal hematopoietic stem and progenitor cells. Moreover, these genes are preferentially upregulated by Decitabine in human primary AML blasts, and control cell proliferation, death and development. <p></p> <b>Conclusions.</b> Our WGBS and WIMSi data analysis approach has identified a set of genes whose is methylation and silencing in AML is reversed by DNMTi. These genes are good candidates for direct regulation by DNMTi, and their reactivation by DNMTi may contribute to therapeutic activity. This study also demonstrates the ability of WIMSi to reveal relationships between DNA methylation and gene expression, based on single-nucleotide bisulfite-sequencing and RNA-seq data.<p></p&gt

Identifying Hail Signatures in Satellite Imagery from the 9-10 August 2011 Severe Weather Event

Severe thunderstorms can produce large hail that causes property damage, livestock fatalities, and crop failure. However, detailed storm surveys of hail damage conducted by the National Weather Service (NWS) are not required. Current gaps also exist between Storm Prediction Center (SPC) hail damage estimates and cropinsurance payouts. NASA's Moderate Resolution Imaging Spectroradiometer (MODIS) instrument aboard the Terra and Aqua satellites can be used to support NWS damage assessments, particularly to crops during the growing season. The twoday severe weather event across western Nebraska and central Kansas during 910 August 2011 offers a case study for investigating hail damage signatures by examining changes in Normalized Difference Vegetation Index (NDVI) derived from MODIS imagery. By analyzing hail damage swaths in satellite imagery, potential economic losses due to crop damage can be quantified and further improve the estimation of weather impacts on agriculture without significantly increasing manpower requirements

Using Satellite Imagery to Identify Tornado Damage Tracks and Recovery from the April 27, 2011 Severe Weather Outbreak

Emergency response to natural disasters requires coordination between multiple local, state, and federal agencies. Single, relatively weak tornado events may require comparatively simple response efforts; but larger "outbreak" events with multiple strong, long-track tornadoes can benefit from additional tools to help expedite these efforts. Meteorologists from NOAA's National Weather Service conduct field surveys to map tornado tracks, assess damage, and determine the tornado intensity following each event. Moderate and high resolution satellite imagery can support these surveys by providing a high-level view of the affected areas. Satellite imagery could then be used to target areas for immediate survey or to corroborate the results of the survey after it is completed. In this study, the feasibility of using satellite imagery to identify tornado damage tracks was determined by comparing the characteristics of tracks observed from low-earth orbit to tracks assessed during the official NWS storm survey process. Of the 68 NWS confirmed centerlines, 24 tracks (35.3%) could be distinguished from other surface features using satellite imagery. Within each EF category, 0% of EF-0, 3% of EF-1, 50% of EF-2, 77.7% of EF-3, 87.5% of EF-4 and 100% of EF-5 tornadoes were detected. It was shown that satellite data can be used to identify tornado damage tracks in MODIS and ASTER NDVI imagery, where damage to vegetation creates a sharp drop in values though the minimum EF-category which can be detected is dependent upon the type of sensor used and underlying vegetation. Near-real time data from moderate resolution sensors compare favorably to field surveys after the event and suggest that the data can provide some value in the assessment process

Verification and Enhancement of VIIRS Day-Night Band (DNB) Power Outage Detection Product

This case study of Hurricane Matthew (October 2016) uses the NASA Short-Term Prediction Research and Transition (SPoRT) Center DNB power outage product (using GSFC VIIRS DNB preliminary Black Marble product, Roman et al.. 2017) and 2013 LandScan Global population data to look for correlations between the post-event %-of-normal radiance and the utility company-reported outage numbers (obtained from EAGLE-1)

Characterization of Nighttime Light Variability Over the Southeastern United States

City lights provide indications of human activity at night. Nighttime satellite imagery offers daily snapshots of this activity. With calibrated, science-quality imagery, long-term monitoring can also be achieved. The degree to which city lights fluctuate, however, is not well known. For the application of detecting power outages, this degree of variability is crucial for assessing reductions to city lights based on historical trends. Eight southeastern U.S. cities are analyzed to understand the relationship between emission variability and several population centers. A preliminary, example case power outage study is also discussed as a transition into future work

Supporting Disaster Assessment and Response with the VIIRS Day-Night Band

When meteorological or manmade disasters occur, first responders often focus on impacts to the affected population and other human activities. Often, these disasters result in significant impacts to local infrastructure and power, resulting in widespread power outages. For minor events, these power outages are often short-lived, but major disasters often include longterm outages that have a significant impact on wellness, safety, and recovery efforts within the affected areas. Staff at NASA's Shortterm Prediction Research and Transition (SPoRT) Center have been investigating the use of the VIIRS daynight band for monitoring power outages that result from significant disasters, and developing techniques to identify damaged areas in near realtime following events. In addition to immediate assessment, the VIIRS DNB can be used to monitor and assess ongoing recovery efforts. In this presentation, we will highlight previous applications of the VIIRS DNB following Superstorm Sandy in 2012, and other applications of the VIIRS DNB to more recent disaster events, including detection of outages following the Moore, Oklahoma tornado of May 2013 and the Chilean earthquake of April 2014. Examples of current products will be shown, along with future work and other goals for supporting disaster assessment and response with VIIRS capabilities

A Src-Like Inactive Conformation in the Abl Tyrosine Kinase Domain

The improper activation of the Abl tyrosine kinase results in chronic myeloid leukemia (CML). The recognition of an inactive conformation of Abl, in which a catalytically important Asp-Phe-Gly (DFG) motif is flipped by approximately 180° with respect to the active conformation, underlies the specificity of the cancer drug imatinib, which is used to treat CML. The DFG motif is not flipped in crystal structures of inactive forms of the closely related Src kinases, and imatinib does not inhibit c-Src. We present a structure of the kinase domain of Abl, determined in complex with an ATP–peptide conjugate, in which the protein adopts an inactive conformation that resembles closely that of the Src kinases. An interesting aspect of the Src-like inactive structure, suggested by molecular dynamics simulations and additional crystal structures, is the presence of features that might facilitate the flip of the DFG motif by providing room for the phenylalanine to move and by coordinating the aspartate side chain as it leaves the active site. One class of mutations in BCR–Abl that confers resistance to imatinib appears more likely to destabilize the inactive Src-like conformation than the active or imatinib-bound conformations. Our results suggest that interconversion between distinctly different inactive conformations is a characteristic feature of the Abl kinase domain

Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions

Background: Age-associated epigenetic changes are implicated in aging. Notably, age-associated DNA methylation changes comprise a so-called aging “clock”, a robust biomarker of aging. However, while genetic, dietary and drug interventions can extend lifespan, their impact on the epigenome is uncharacterised. To fill this knowledge gap, we defined age-associated DNA methylation changes at the whole-genome, single-nucleotide level in mouse liver and tested the impact of longevity-promoting interventions, specifically the Ames dwarf Prop1 df/df mutation, calorie restriction and rapamycin. Results: In wild-type mice fed an unsupplemented ad libitum diet, age-associated hypomethylation was enriched at super-enhancers in highly expressed genes critical for liver function. Genes harbouring hypomethylated enhancers were enriched for genes that change expression with age. Hypermethylation was enriched at CpG islands marked with bivalent activating and repressing histone modifications and resembled hypermethylation in liver cancer. Age-associated methylation changes are suppressed in Ames dwarf and calorie restricted mice and more selectively and less specifically in rapamycin treated mice. Conclusions: Age-associated hypo- and hypermethylation events occur at distinct regulatory features of the genome. Distinct longevity-promoting interventions, specifically genetic, dietary and drug interventions, suppress some age-associated methylation changes, consistent with the idea that these interventions exert their beneficial effects, in part, by modulation of the epigenome. This study is a foundation to understand the epigenetic contribution to healthy aging and longevity and the molecular basis of the DNA methylation clock