415 research outputs found
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)
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>
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
An Epigenetic Pilot Study Investigating Biomarkers in Maternal-Infant Pairs
Rationale: Particulate matter (PM) is a measurable component of air pollution that has been associated with adverse cardiovascular and respiratory outcomes. Research indicates environmental factors such as air pollution are involved in changes through epigenetic mechanisms during development that may persist into adulthood and even span multiple generations of inheritance. Epigenetics is the study of heritable changes of gene expression that do not alter the actual DNA sequence. One epigenetic mechanism is DNA methylation. Long Interspersed Nuclear Element (LINE-1) is a DNA repetitive element that can be used as a proxy measurement of DNA global methylation.
The purpose of this pilot study was to compare epigenetic biomarkers across different sample matrices (i.e. blood and buccal) and across related subjects (i.e. maternal and infant).
Methods: Informed consent was provided by pregnant women (n=23) who were recruited through Women, Infants, and Children (WIC), hospital birthing classes, or flyers in obstetrician’s offices. Demographic and medical data was collected from hospital records for both mothers and newborns after birth. Follow-up health surveys were administered by telephone that were designed to collect indicators of pre-asthmatic respiratory symptoms or conditions.
Biological samples were collected before or shortly after time of birth at Community Medical Center of Missoula, MT. The samples collected were maternal blood (n=15), umbilical cord blood (n=15), and maternal (n=23) and newborn (n=23) buccal (cheek) cells. Buccal cells were collected and processed according to the Gentra Puregene Kit (Qiagen, Germantown, MD). These biologically accessible tissues serve as surrogates to study gene methylation associated with respiratory health.
Samples were stored at -80°C until DNA extraction and subsequent bisulfite treatment. The samples were amplified in duplicates with polymerase chain reaction (PCR). LINE-1 methylation was analyzed with pyrosequencing on a Pyromark Q96 MD (Qiagen, Germantown, MD). All statistical analysis was performed in Statistical Analysis Software (SAS, version 9.3).
Results: The mean (standard deviation (sd)) of LINE-1 methylation percentage for mother and infant buccal cell derived DNA were 58.75 (3.89) and 57.16 (2.54), respectively. Percent methylation maximum for mother and infant buccal samples were 70.22 and 64.25, respectively, and minimum were 54.86 and 52.94, respectively. Paired t-test indicated that LINE-1 methylation percentages in maternal buccal samples were higher than methylation percentages in the paired infant samples (mean difference (95%CL) = 4.4 (2.3, 6.6)).
The mean (sd) of LINE-1 methylation percentage for mother and infant/cord blood derived DNA were 75.19 (3.17) and 75.86 (3.05), respectively. Percent methylation maximum for mother and infant blood samples were 79.42 and 79.50, respectively, and minimum were 70.39 and 69.31, respectively. Paired t-test indicated that LINE-1 methylation percentages in maternal blood samples were similar to methylation percentages in infant blood samples (mean difference (95% CL) = 0.66 (-2.0,3.3)).
Conclusions: LINE-1 methylation percentages between sample matrices (i.e. blood and buccal) and subjects (i.e. maternal and infant) were not correlated. The percent methylation of LINE-1 in DNA from blood was consistently greater than for DNA from buccal tissue for both mother and newborn samples. It was expected that LINE-1 measurements for blood DNA would differ from buccal DNA because circulating blood represents a more diverse cell population. Gene-specific methylation of the promoter region for interferon-γ, a cytokine associated with asthma, will be studied with the remaining samples of bisulfite-treated DNA from this study. Epigenetic changes may serve as useful biomarkers for predicting asthma risk in children exposed to biomass smoke. These methods can be applied to future studies to investigate the epigenetic relationship of prenatal asthma risk and PM wood smoke exposure
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
International Space Station (ISS) Internal Active Thermal Control System (IATCS) New Biocide Selection, Qualification and Implementation
The Internal Active Thermal Control System (IATCS) aboard the International Space Station (ISS) is primarily responsible for the removal of heat loads from payload and system racks. The IATCS is a water based system which works in conjunction with the EATCS (External ATCS), an ammonia based system, which are interfaced through a heat exchanger to facilitate heat transfer. On-orbit issues associated with the aqueous coolant chemistry began to occur with unexpected increases in CO2 levels in the cabin. This caused an increase in total inorganic carbon (TIC), a reduction in coolant pH, increased corrosion, and precipitation of nickel phosphate. These chemical changes were also accompanied by the growth of heterotrophic bacteria that increased risk to the system and could potentially impact crew health and safety. Studies were conducted to select a biocide to control microbial growth in the system based on requirements for disinfection at low chemical concentration (effectiveness), solubility and stability, material compatibility, low toxicity to humans, compatibility with vehicle environmental control and life support systems (ECLSS), ease of application, rapid on-orbit measurement, and removal capability. Based on these requirements, ortho-phthalaldehyde (OPA), an aromatic dialdehyde compound, was selected for qualification testing. This paper presents the OPA qualification test results, development of hardware and methodology to safely apply OPA to the system, development of a means to remove OPA, development of a rapid colorimetric test for measurement of OPA, and the OPA on-orbit performance for controlling the growth of microorganisms in the ISS IATCS since November 3, 2007
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
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