Propagating the Haze? Community and professional perceptions of cannabis cultivation and the impacts of prohibition

Recent decades have seen substantial changes in the UK cannabis landscape, including increased domestic production, the ascendancy of stronger strains (namely ‘skunk’) and the drug’s re-reclassification under the 1971 Misuse of Drugs Act. Resultantly, cannabis retains significance in the consciousness, priorities and policy agendas of communities, drug services and criminal justice agencies. This paper presents an empirical study, which examined both perceptions and impacts of cannabis cultivation and its control within a North-West English borough. Drawing on qualitative research with professionals, practitioners, resident groups, cannabis users, cannabis users’ families and cannabis cultivators themselves, the findings suggest that cannabis cultivation was not a uniformly familiar concept to respondents, who had limited knowledge and experience of its production. Across all participant groups, the transmission of accurate information was lacking, with individuals instead drawing on the reductionist drug discourse (Taylor, 2016) to fill knowledge deficits. Consequently, some participants conflated cannabis cultivation with wider prohibitionist constructions of drug markets, resulting in the diffusion of misinformation and an amplification of anxieties. In contrast, other participants construed cultivation as making economic sense during austerity, justifying such tolerance through inverse adherence to the same narrow socio-cultural construction of drugs i.e. that cultivation carried comparatively less harms than real drug markets. Enforcement mechanisms also drew on generic prohibitionist conceptions, assuming cultivators to be unconstrained, autonomous actors in need of punishment; a belief which lacked nuanced understanding of the local terrain where vulnerable individuals cultivating under duress played a key role in the supply chain. The paper concludes with a call for the provision of accessible information/education; the need to challenge and reconceptualise the assumed autonomy and resultant punity directed at all cultivators; and a subsequent need to reassess established forms of legal (and increasingly social) enforcement

Cannabis Use in an English Community: Acceptance, Anxieties and the Liminality of Drug Prohibition

Cannabis occupies an ambiguous social, cultural, economic and legal position, meaning that the way communities construct, interact with and interpret drug markets is a complicated and uncertain process. This article seeks to explain these ambiguities by investigating the place of cannabis use in a UK borough, drawing on qualitative empirical data collated from a sample (n=68) of practitioners, local residents, cannabis users and their families. In doing so, the article employs the concept of liminality (whereby individuals and spaces occupy a position at both ends of a threshold) to explore how community behaviours and norms relate to issues of space, harm and drug policy. The article contextualises the position of cannabis use within the fieldwork site, exploring a series of competing contradictions that divided participants between the rhetoric and reality of drug prohibition. Drug prohibition suggests cannabis use to be dangerous, which prompted concern. However, the lived reality of prohibition for residents sat in stark juxtaposition: the drug was used commonly and publicly; was effectively decriminalised; and its use (reluctantly) accommodated. This malaise placed residents within what is described here as the liminality of drug prohibition, in which notions of the licit and illicit became blurred and whereby the illegality of cannabis augmented anxieties yet simultaneously proved a barrier to addressing them. In conclusion, the current study provides further evidence of prohibitionist drug policy proliferating rather than mitigating drug related harms

Granulosa cell tumor of the ovary: time to launch a new prospective trial

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By hook or by crook? Morphometry, competition and cooperation in rodent sperm

Background Sperm design varies enormously across species and sperm competition is thought to be a major factor influencing this variation. However, the functional significance of many sperm traits is still poorly understood. The sperm of most murid rodents are characterised by an apical hook of the sperm head that varies markedly in extent across species. In the European woodmouse Apodemus sylvaticus (Muridae), the highly reflected apical hook of sperm is used to form sperm groups, or “trains,” which exhibited increased swimming velocity and thrusting force compared to individual sperm. Methodology/Principal Findings Here we use a comparative study of murine rodent sperm and demonstrate that the apical hook and sperm cooperation are likely to be general adaptations to sperm competition in rodents. We found that species with relatively larger testes, and therefore more intense sperm competition, have a longer, more reflected apical sperm hook. In addition, we show that sperm groups also occur in rodents other than the European woodmouse. Conclusions Our results suggest that in rodents sperm cooperation is more widespread than assumed so far and highlight the importance of diploid versus haploid selection in the evolution of sperm design and function

Sperm design and variation in the New World blackbirds (Icteridae)

Post-copulatory sexual selection (PCSS) is thought to be one of the evolutionary forces responsible for the rapid and divergent evolution of sperm design. However, whereas in some taxa particular sperm traits are positively associated with PCSS, in other taxa, these relationships are negative, and the causes of these different patterns across taxa are poorly understood. In a comparative study using New World blackbirds (Icteridae), we tested whether sperm design was influenced by the level of PCSS and found significant positive associations with the level of PCSS for all sperm components but head length. Additionally, whereas the absolute length of sperm components increased, their variation declined with the intensity of PCSS, indicating stabilizing selection around an optimal sperm design. Given the diversity of, and strong selection on, sperm design, it seems likely that sperm phenotype may influence sperm velocity within species. However, in contrast to other recent studies of passerine birds, but consistent with several other studies, we found no significant link between sperm design and velocity, using four different species that vary both in sperm design and PCSS. Potential reasons for this discrepancy between studies are discussed

Antivirals Reduce the Formation of Key Alzheimer's Disease Molecules in Cell Cultures Acutely Infected with Herpes Simplex Virus Type 1

Alzheimer's disease (AD) afflicts around 20 million people worldwide and so there is an urgent need for effective treatment. Our research showing that herpes simplex virus type 1 (HSV1) is a risk factor for AD for the brains of people who possess a specific genetic factor and that the virus causes accumulation of key AD proteins (β-amyloid (Aβ) and abnormally phosphorylated tau (P-tau)), suggests that anti-HSV1 antiviral agents might slow AD progression. However, currently available antiviral agents target HSV1 DNA replication and so might be successful in AD only if Aβ and P-tau accumulation depend on viral DNA replication. Therefore, we investigated firstly the stage(s) of the virus replication cycle required for Aβ and P-tau accumulation, and secondly whether antiviral agents prevent these changes using recombinant strains of HSV1 that progress only partly through the replication cycle and antiviral agents that inhibit HSV1 DNA replication. By quantitative immunocytochemistry we demonstrated that entry, fusion and uncoating of HSV1, are insufficient to induce Aβ and P-tau production. We showed also that none of the “immediate early” viral proteins is directly responsible, and that Aβ and P-tau are produced at a subsequent stage of the HSV1 replication cycle. Importantly, the anti-HSV1 antiviral agents acyclovir, penciclovir and foscarnet reduced Aβ and P-tau accumulation, as well as HSV1, with foscarnet being less effective in each case. P-tau accumulation was found to depend on HSV1 DNA replication, whereas Aβ accumulation was not. The antiviral-induced decrease in Aβ is attributable to the reduced number of new viruses, and hence the reduction in viral spread. Since antiviral agents reduce greatly Aβ and P-tau accumulation in HSV1-infected cells, they would be suitable for treating AD with great advantage unlike current AD therapies, only the virus, not the host cell, would be targeted

Human Mas-related G protein-coupled receptors-X1 induce chemokine receptor 2 expression in rat dorsal root ganglia neurons and release of chemokine ligand 2 from the human LAD-2 mast cell line

Primate-specific Mas-related G protein-coupled receptors-X1 (MRGPR-X1) are highly enriched in dorsal root ganglia (DRG) neurons and induce acute pain. Herein, we analyzed effects of MRGPR-X1 on serum response factors (SRF) or nuclear factors of activated T cells (NFAT), which control expression of various markers of chronic pain. Using HEK293, DRG neuron-derived F11 cells and cultured rat DRG neurons recombinantly expressing human MRGPR-X1, we found activation of a SRF reporter gene construct and induction of the early growth response protein-1 via extracellular signal-regulated kinases-1/2 known to play a significant role in the development of inflammatory pain. Furthermore, we observed MRGPR-X1-induced up-regulation of the chemokine receptor 2 (CCR2) via NFAT, which is considered as a key event in the onset of neuropathic pain and, so far, has not yet been described for any endogenous neuropeptide. Up-regulation of CCR2 is often associated with increased release of its endogenous agonist chemokine ligand 2 (CCL2). We also found MRGPR-X1-promoted release of CCL2 in a human connective tissue mast cell line endogenously expressing MRGPR-X1. Thus, we provide first evidence to suggest that MRGPR-X1 induce expression of chronic pain markers in DRG neurons and propose a so far unidentified signaling circuit that enhances chemokine signaling by acting on two distinct yet functionally co-operating cell types. Given the important role of chemokine signaling in pain chronification, we propose that interruption of this signaling circuit might be a promising new strategy to alleviate chemokine-promoted pain

Cosmogenic neutron production at the Sudbury Neutrino Observatory

Neutrons produced in nuclear interactions initiated by cosmic-ray muons present an irreducible background to many rare-event searches, even in detectors located deep underground. Models for the production of these neutrons have been tested against previous experimental data, but the extrapolation to deeper sites is not well understood. Here we report results from an analysis of cosmogenically produced neutrons at the Sudbury Neutrino Observatory. A specific set of observables are presented, which can be used to benchmark the validity of geant4 physics models. In addition, the cosmogenic neutron yield, in units of 10-4 cm2/(g·μ), is measured to be 7.28±0.09(stat)-1.12+1.59(syst) in pure heavy water and 7.30±0.07(stat)-1.02+1.40(syst) in NaCl-loaded heavy water. These results provide unique insights into this potential background source for experiments at SNOLAB

APP Processing Induced by Herpes Simplex Virus Type 1 (HSV-1) Yields Several APP Fragments in Human and Rat Neuronal Cells

Lifelong latent infections of the trigeminal ganglion by the neurotropic herpes simplex virus type 1 (HSV-1) are characterized by periodic reactivation. During these episodes, newly produced virions may also reach the central nervous system (CNS), causing productive but generally asymptomatic infections. Epidemiological and experimental findings suggest that HSV-1 might contribute to the pathogenesis of Alzheimer's disease (AD). This multifactorial neurodegenerative disorder is related to an overproduction of amyloid beta (Aβ) and other neurotoxic peptides, which occurs during amyloidogenic endoproteolytic processing of the transmembrane amyloid precursor protein (APP). The aim of our study was to identify the effects of productive HSV-1 infection on APP processing in neuronal cells. We found that infection of SH-SY5Y human neuroblastoma cells and rat cortical neurons is followed by multiple cleavages of APP, which result in the intra- and/or extra-cellular accumulation of various neurotoxic species. These include: i) APP fragments (APP-Fs) of 35 and 45 kDa (APP-F35 and APP-F45) that comprise portions of Aβ; ii) N-terminal APP-Fs that are secreted; iii) intracellular C-terminal APP-Fs; and iv) Aβ1-40 and Aβ1-42. Western blot analysis of infected-cell lysates treated with formic acid suggests that APP-F35 may be an Aβ oligomer. The multiple cleavages of APP that occur in infected cells are produced in part by known components of the amyloidogenic APP processing pathway, i.e., host-cell β-secretase, γ-secretase, and caspase-3-like enzymes. These findings demonstrate that HSV-1 infection of neuronal cells can generate multiple APP fragments with well-documented neurotoxic potentials. It is tempting to speculate that intra- and extracellular accumulation of these species in the CNS resulting from repeated HSV-1 reactivation could, in the presence of other risk factors, play a co-factorial role in the development of AD