A Comparison of Antioxidant Potential, Total Phenolic Content, and Cannabidiol (CBD) Content of Cannabis Infused Hemp, MCT, and Olive Oils

The Cannabis industry has seen immense growth in recent years and research on this plant and its constituents has been growing to keep up with industry demand. The majority of research has focused on commercial-scale products and industrial processing, but there is a lack of research on the smaller scale manufacturing side of the Cannabis industry that includes homemade Cannabis products. Popular Cannabis products are oil-based tinctures that are made by infusing Cannabis plant material in a heated source of edible oil. The types of oils used for this process vary, and there is not an established standardized oil type that has been shown to be the optimal choice for reaping the most benefits from Cannabis infusion. The goal of infusing Cannabis in oil is to extract the desirable potentially neurologically active cannabinoid plant molecules that also serve as antioxidants, specifically cannabidiol (CBD). To determine the effect of oil type on extraction ability of Cannabis, different oil types were used to infuse a high-CBD strain of Cannabis and measure antioxidant potential, total phenolic content, and CBD content of the resulting oils. Hemp oil, MCT oil, and olive oil were used as infusion solvents for the ground decarboxylated Cannabis flowers. Consistency in the protocol was followed for the strain of Cannabis, decarboxylation process, grinding process, heated infusion process, and storage conditions. Additionally, control standards were established by implementing the heating process for the oils without Cannabis infusion. Antioxidant potential was assessed using Trolox Equivalent Antioxidant Capacity (TEAC) assay, and total phenolic content was assessed using Gallic Acid Equivalence (GAE) assay. CBD content of the CBD oils was assessed using high-performance liquid chromatography with ultraviolet detection (HPLC-UV). For antioxidant potential, hemp CBD oil had the greatest antioxidant potential, but the other CBD oils had a significant increase in antioxidant potential compared to their control oils whereas hemp CBD oil did not. For total phenolic content, olive CBD oil had the highest total phenolic content. For CBD content, hemp CBD oil and olive CBD oil had the highest CBD content

Tetramerisation of the CRISPR ring nuclease Crn3/Csx3 facilitates cyclic oligoadenylate cleavage

Type III CRISPR systems detect foreign RNA and activate the cyclase domain of the Cas10 subunit, generating cyclic oligoadenylate (cOA) molecules that act as a second messenger to signal infection, activating nucleases that degrade the nucleic acid of both invader and host. This can lead to dormancy or cell death; to avoid this, cells need a way to remove cOA from the cell once a viral infection has been defeated. Enzymes specialised for this task are known as ring nucleases, but are limited in their distribution. Here, we demonstrate that the widespread CRISPR associated protein Csx3, previously described as an RNA deadenylase, is a ring nuclease that rapidly degrades cyclic tetra-adenylate (cA4). The enzyme has an unusual cooperative reaction mechanism involving an active site that spans the interface between two dimers, sandwiching the cA4 substrate. We propose the name Crn3 (CRISPR associated ring nuclease 3) for the Csx3 family.Publisher PDFPeer reviewe

The dynamic interplay of host and viral enzymes in type III CRISPR-mediated cyclic nucleotide signalling

This work was supported by a grant from the Biotechnology and Biological Sciences Research Council (Grant REF BB/S000313/1 to MFW) and the Wellcome Trust (Grant 210486/Z/18/Z to CMC).Cyclic nucleotide second messengers are increasingly implicated in prokaryotic anti-viral defence systems. Type III CRISPR systems synthesise cyclic oligoadenylate (cOA) upon detecting foreign RNA, activating ancillary nucleases that can be toxic to cells, necessitating mechanisms to remove cOA in systems that operate via immunity rather than abortive infection. Previously, we demonstrated that the Sulfolobus solfataricus type III-D CRISPR complex generates cyclic tetra-adenylate (cA4), activating the ribonuclease Csx1, and showed that subsequent RNA cleavage and dissociation acts as an ‘off-switch’ for the cyclase activity. Subsequently, we identified the cellular ring nuclease Crn1, which slowly degrades cA4 to reset the system (Rouillon et al., 2018), and demonstrated that viruses can subvert type III CRISPR immunity by means of a potent anti-CRISPR ring nuclease variant AcrIII-1. Here, we present a comprehensive analysis of the dynamic interplay between these enzymes, governing cyclic nucleotide levels and infection outcomes in virus-host conflict.Publisher PDFPeer reviewe

A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer

Brain metastases represent an important cause of morbidity in patients with lung cancer and are associated with a mean survival of less than 6 months. Thus, new regimens improving the outcome of these patients are urgently needed. On the basis of promising data raised in a phase I/II trial, we initiated an open, randomised, prospective, multicentric phase III trial, comparing whole brain radiation therapy (WBRT; 20 × 2 Gy) alone with WBRT+topotecan (RCT; 0.4 mg m−2 day−1 × 20). A total of 320 patients with CNS-metastases due to SCLC or NSCLC were projected. The primary end point was overall survival, whereas second end points were local response and progression-free survival. However, until the cutoff date of study completion (i.e., a study duration of 34 months), only a total of 96 (RCT:47, WBRT:49) patients had been recruited, and so an analysis was performed at that time point. Although the numbers of grade 3/4 non-haematological toxicities (besides alopecia 115 (RCT/WBRT: 55 out of 60) were evenly distributed, the 25 haematological events occurred mainly in the combined treatment arm (24 out of 1). Local response, evaluated 2 weeks after treatment, was assessable in 44 (RCT/WBRT: 23 out of 21) patients, showing CR in eight (3 out of 5), PR in 17 (11 out of 6), SD in 14 (8 out of 6) and PD in five (1 out of 4) patients (all differences n.s.). Neither OAS (RCT/WBRT: median (days)): 87 out of 95, range 3–752/4–433; HR 1.32; 95% CI (0.83; 2.10)) nor PFS (median (days)): 71 out of 66, range, 3–399/4–228; HR 1.28, 95% CI (0.73; 2.43) differed significantly. On the basis of these results and the slow recruitment, a continuation of the study did not seem reasonable. The available data show no significant advantage for concurrent radiochemotherapy for patients with lung cancer; however, the recruited number of patients is too low to exhibit a small advantage of combined treatment

Peace on Earth and goodwill toward men: altruism of long term volunteers

A grounded theory approach was taken to formulating a new theoretical framework of altruism based on twelve in-depth interviews with a heterogenous group of long term volunteers from a single community. Interviews were first analyzed separately to construct a clear sense of each individuals??? motivations for volunteering, then commonalities were identified and integrated with past research on both volunteer moti- vations and altruism. The emergent motives from interviews largely aligned with core psychological needs as described by Self Determination Theory, motives to volunteer as identified by work on the Volunteer Functions Inventory, or role identification in accordance with Social Identity Theory. An integrated frame- work was formulated by integrating these three elements along with other relevant observations from the interview responses. Most volunteers interviewed saw their own actions as having a self-centered motivation. This observation along with the integrated framework of Self Determination theory is used to highlight that the emotional or regulatory processes which volunteers rely upon to maintain their volunteering may be self focused while the overall behavioral patten may still be altruistic, or other serving

Effect of Residential Proximity and Exposure to Municipal, Industrial, and Hazardous Waste Sites on Cancer Risk: A Literature Review

The term “waste” encompasses a large array of materials, chemicals, and byproducts that are no longer of use. Waste is generated every day, by every individual, all around the world. There are different techniques of managing waste; there is concern that certain forms of waste management present a threat to the health of humans. Several studies have examined the health risks associated with waste and waste management, specifically hazardous waste. Certain geographical areas are more heavily populated with waste disposal sites, and the individuals residing in those areas may be at an increased risk for diseases such as cancer. Municipal, industrial, and hazardous waste has been linked to an increased risk for many cancer types. Given the vast amount of waste generated daily around the world, it is important to understand and analyze the existing body of literature on the risk of cancer for individuals residing in close proximity to waste sites. With the focus of residential proximity to municipal, industrial, and hazardous waste, a PubMed literature search performed in September of 2022 yielded 70 articles that examined the risk of cancer; 10 of the articles met the inclusion criteria for this review. Estimations of risk, incidence, and mortality of cancer in the United States and European countries ranged from strong positive associations with an odds ratio of 31.4, to null associations that indicated no risk. Eight of the ten studies that were analyzed found positive associations, one study resulted in mixed results, and one study resulted in non-significant results. Among adult and children populations, an increased risk of cancer was observed for non-Hodgkin’s lymphoma (NHL), soft-tissue sarcomas (STSs), and lung, liver, kidney, bone, bladder, gastric, and renal cancers. The positive findings among previous literature indicate that it is of public health significance to continue to investigate the relationship between residential proximity to the environmental exposures of waste and the risk of cancer. Public health regulations and policies can be developed that will reduce adverse health outcomes and diseases such as cancer by conducting further research on this relationship

The CRISPR ancillary effector Can2 is a dual-specificity nuclease potentiating type III CRISPR defence

Funding: Biotechnology and Biological Sciences Research Council [BB/S000313/1 to M.F.W., BB/T004789/1 to M.F.W. and T.M.G.]; Wellcome Trust Institutional Strategic Support Funding [204821/Z/16/Z to M.F.W. and T.M.G.]; China Scholarship Council [201703780015 to W.Z.]. Funding for open access charge: RCUK block grant.Cells and organisms have a wide range of mechanisms to defend against infection by viruses and other mobile genetic elements (MGE). Type III CRISPR systems detect foreign RNA and typically generate cyclic oligoadenylate (cOA) second messengers that bind to ancillary proteins with CARF (CRISPR associated Rossman fold) domains. This results in the activation of fused effector domains for antiviral defence. The best characterised CARF family effectors are the Csm6/Csx1 ribonucleases and DNA nickase Can1. Here we investigate a widely distributed CARF family effector with a nuclease domain, which we name Can2 (CRISPR ancillary nuclease 2). Can2 is activated by cyclic tetra-adenylate (cA4) and displays both DNase and RNase activity, providing effective immunity against plasmid transformation and bacteriophage infection in Escherichia coli. The structure of Can2 in complex with cA4 suggests a mechanism for the cA4-mediated activation of the enzyme, whereby an active site cleft is exposed on binding the activator. These findings extend our understanding of type III CRISPR cOA signalling and effector function.Publisher PDFPeer reviewe

Biogenesis of the Unique 4′,5′-Dehydronucleoside of the Uridyl Peptide Antibiotic Pacidamycin

The pacidamycins belong to a class of antimicrobial nucleoside antibiotics that act by inhibiting the clinically unexploited target translocase I, a key enzyme in peptidoglycan assembly. As with other nucleoside antibiotics, the pacidamycin 4',5'-dehydronucleoside portion is an essential pharmacophore. Here we show that the biosynthesis of the pacidamycin nucleoside in Streptomyces coeruleorubidus proceeds through three steps from uridine. The transformations involve oxidation of the 5'-alcohol by Pac11, transamination of the resulting aldehyde by Pac5, and dehydration by the Cupin-domain protein Pac13.</p

Health Insurance Coverage of Recommended Gender-Affirming Health Care Services for Transgender Youth: Shopping Online for Coverage Information

We assessed online health insurance plan indication of coverage and accessibility of information for recommended services for transgender youth (TY). Content analysis was performed for plans used at a pediatric Gender Clinic by reviewing information about coverage of puberty blockers, hormones, masculinizing chest surgery, and counseling. Transgender-specific exclusions and the time required for the research assistant to review each plan's online information were noted. No plan (0%; n=36) indicated coverage of all four categories of recommended services online. Forty-nine percent indicated ≥1 transgender-specific exclusion. The median time required for a research assistant to review online coverage information for each insurance plan was 50 min. Efforts are needed to ensure that online insurance information is accessible and updated in accordance with policy and coverage recommendations for TY

Isolating antifungals from fungus-growing ant symbionts using a genome-guided chemistry approach

We describe methods used to isolate and identify antifungal compounds from actinomycete strains associated with the leaf-cutter ant Acromyrmex octospinosus. These ants use antibiotics produced by symbiotic actinomycete bacteria to protect themselves and their fungal cultivar against bacterial and fungal infections. The fungal cultivar serves as the sole food source for the ant colony, which can number up to tens of thousands of individuals. We describe how we isolate bacteria from leaf-cutter ants collected in Trinidad and analyze the antifungal compounds made by two of these strains (Pseudonocardia and Streptomyces spp.), using a combination of genome analysis, mutagenesis, and chemical isolation. These methods should be generalizable to a wide variety of insect-symbiont situations. Although more time consuming than traditional activity-guided fractionation methods, this approach provides a powerful technique for unlocking the complete biosynthetic potential of individual strains and for avoiding the problems of rediscovery of known compounds. We describe the discovery of a novel nystatin compound, named nystatin P1, and identification of the biosynthetic pathway for antimycins, compounds that were first described more than 60 years ago. We also report that disruption of two known antifungal pathways in a single Streptomyces strain has revealed a third, and likely novel, antifungal plus four more pathways with unknown products. This validates our approach, which clearly has the potential to identify numerous new compounds, even from well-characterized actinomycete strains