Introduction: Several studies have found that cannabinoids, particularly delta-9-tetrahydrocannabinol and cannabidiol (CBD), have the ability to reduce cancer cell viability. An ongoing debate regarding the use of medical Cannabis revolves around the effectiveness of pure compounds versus intact plant material for treatment. Proponents for the use of intact plant material or botanical extracts argue that there is a synergistic effect between the different cannabinoids, terpenoids, and flavonoids; this is commonly referred to as the "entourage effect." Our study was designed to test the validity of the proposed entourage effect in a narrow application using a cancer cell viability model. Materials and Methods: Six cancer cell lines, from 3 different types of human cancer were treated with 10 μM pure CBD or 10 μM CBD from hemp (Cannabis sativa) oil (obtained from 3 different commercial sources) for 48 h, and cell viability was measured with the MTS assay. Dose-response curves were then performed to compare the potencies of pure CBD to CBD oils. CBD concentrations were independently confirmed in the commercial oils, and cannabinoid and terpene composition were also compared. Results: CBD (10 μM) was able to reduce cell viability in 3 of the 6 cell lines tested, and this was found to be cell line specific and not specific to select cancers. None of the CBD oils tested were able to reduce viability to a greater extent than that of pure CBD. Additionally, dose-response curves found lower IC 50 values for pure CBD compared to the most potent CBD oil tested. Interestingly, some oils actually appeared to protect cancer cells from the effects of CBD. Conclusions: We found that pure CBD was as potent or more potent at reducing cancer cell viability as the most potent oil tested, suggesting that there is no "entourage" effect under these specific in vitro conditions.
Shipwrecks with wooden hulls are underrepresented in the archaeological record from shallow federal waters of the central and western Gulf of Mexico (defined as less than 600 feet deep), yet they tend to be older and arguably more abundant than shipwrecks with metal hulls. This paper quantifies the extent of bias in favor of metal hulls in the archaeological record; examines its potential causes; discusses factors affecting the preservation and discovery of wooden hulls; and proposes a research strategy that might accelerate discoveries of wood-hulled shipwrecks. IntroductionThe waters of the central and western Gulf of Mexico have been extensively studied by archaeologists for several decades ( Figure 1). This is largely due to the intensity of oil and gas production in the area. The Bureau of Ocean Energy Management, Regulation and Enforcement (BOEMRE) regularly sponsors archaeological studies in addition to reviewing archaeological reports submitted on behalf of oil and gas operators in connection with offshore energy leases. Figure 1 shows locations of roughly 7,000 geo-hazard surveys conducted by the oil and gas industry in the central and western Gulf of Mexico. Each of the smallest colored squares in Figure 1 represents a 3x3-mile mineral lease block. Archaeologists have reviewed geophysical data and prepared archaeological assessment reports for 3,161 lease blocks (those colored blue or purple). Green blocks have been surveyed for geo-hazards but have not been assessed by an archaeologist. Pipeline route surveys are not included in Figure 1. BOEMRE also maintains a GIS database that includes over 3,000 historic reports of vessels lost, over 6,000 Coast Guard hazards to navigation, and over 17,000 net hangs reported by fishing trawlers. As a result of such studies, a great deal is known about the archaeology of this area.The BOEMRE database (2007) contains locations for 195 shipwrecks in the central and western Gulf of Mexico, including 12 wooden shipwrecks (Table 1; 7 shallow and 5 deep) and at least 91 wrecks believed to have metal hulls (74 shallow and 17 deep). Twelve percent of shipwrecks in shallow and deep waters, combined, have wooden hulls. In shallow water the proportion of wooden shipwrecks is 9 percent, and in deep water it is 23 percent. Thirty-one wrecks, all of which are visible on sonar, are confirmed as metal by the BOEMRE database. Another 60 are presumed to be metal from their descriptions or because they have prominent ship-shaped sonar targets that clearly resemble sunken vessels. Wood does not survive exposure in shallow Gulf waters for more than a few years, thus sonar images are unlikely for any except recent wooden hulls in shallow water. Information regarding the other database entries is insufficient to suggest the composition of their hulls.Historic records summarized below indicate that prior to the mid-twentieth century shipwrecks with wooden hulls outnumbered those with metal hulls by 13 to 1. Yet metal hulls in the archaeological record appear to outnumber wooden hulls by ab...
IntroductionBromodomain-containing Protein 4 (BRD4) is a transcriptional regulator which coordinates gene expression programs controlling cancer biology, inflammation, and fibrosis. In the context of airway viral infection, BRD4-specific inhibitors (BRD4i) block the release of pro-inflammatory cytokines and prevent downstream epithelial plasticity. Although the chromatin modifying functions of BRD4 in inducible gene expression have been extensively investigated, its roles in post-transcriptional regulation are not well understood. Given BRD4's interaction with the transcriptional elongation complex and spliceosome, we hypothesize that BRD4 is a functional regulator of mRNA processing.MethodsTo address this question, we combine data-independent analysis - parallel accumulation-serial fragmentation (diaPASEF) with RNA-sequencing to achieve deep and integrated coverage of the proteomic and transcriptomic landscapes of human small airway epithelial cells exposed to viral challenge and treated with BRD4i.ResultsWe discover that BRD4 regulates alternative splicing of key genes, including Interferon-related Developmental Regulator 1 (IFRD1) and X-Box Binding Protein 1 (XBP1), related to the innate immune response and the unfolded protein response (UPR). We identify requirement of BRD4 for expression of serine-arginine splicing factors, splicosome components and the Inositol-Requiring Enzyme 1 IREα affecting immediate early innate response and the UPR.DiscussionThese findings extend the transcriptional elongation-facilitating actions of BRD4 in control of post-transcriptional RNA processing via modulating splicing factor expression in virus-induced innate signaling.
Interpreting remote sensing data is one of the most important tasks of archaeologists working in submerged environments. Researchers rely on remote-sensing technologies to aid their search for historic shipwrecks of interest. Magnetometers are essential for detection of buried shipwrecks. The main goal of magnetic interpretation has been to distinguish shipwrecks from debris, usually resulting in an archaeological assessment of each anomaly concerning its potential for historic significance. The past two decades have seen improvement in archaeologists' abilities to detect shipwreck anomalies. This article provides a basic, nonmathematical summary of magnetism relevant to archaeological interpretation and the evolving perceptions of shipwreck anomalies. The basis for assessing magnetic anomaly significance must be firmly rooted in empiricism in order to improve the objectivity of data interpretation.
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