Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats

Rationale The appetite-stimulating properties of cannabis are well documented and have been predominantly attributed to the hyperphagic activity of the psychoactive phytocannabinoid, ∆9-tetrahydrocannabinol (∆9-THC). However, we have previously shown that a cannabis extract devoid of ∆9-THC still stimulates appetite, indicating that other phytocannabinoids also elicit hyperphagia. One possible candidate is the non-psychoactive phytocannabinoid cannabigerol (CBG), which has affinity for several molecular targets with known involvement in the regulation of feeding behaviour. Objectives The objective of the study was to assess the effects of CBG on food intake and feeding pattern microstructure. Methods Male Lister hooded rats were administered CBG (30–120 mg/kg, per ora (p.o.)) or placebo and assessed in open field, static beam and grip strength tests to determine a neuromotor tolerability profile for this cannabinoid. Subsequently, CBG (at 30–240 mg/kg, p.o.) or placebo was administered to a further group of pre-satiated rats, and hourly intake and meal pattern data were recorded over 2 h. Results CBG produced no adverse effects on any parameter in the neuromotor tolerability test battery. In the feeding assay, 120–240 mg/kg CBG more than doubled total food intake and increased the number of meals consumed, and at 240 mg/kg reduced latency to feed. However, the sizes or durations of individual meals were not significantly increased. Conclusions Here, we demonstrate for the first time that CBG elicits hyperphagia, by reducing latency to feed and increasing meal frequency, without producing negative neuromotor side effects. Investigation of the therapeutic potential of CBG for conditions such as cachexia and other disorders of eating and body weight regulation is thus warranted

Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea

Rationale: Anticipatory nausea (AN) is a poorly controlled side-effect experienced by chemotherapy patients. Currently, pharmacotherapy is restricted to benzodiazepine anxiolytics, which have limited efficacy, significant sedative effects, and induce dependency. The non-psychoactive phytocannabinoid, cannabidiolic acid (CBDA), has shown considerable efficacy in pre-clinical AN models, however determination of its neuromotor tolerability profile is crucial to justify clinical investigation. Provisional evidence for appetite-stimulating properties also requires detailed investigation. Objectives: To assess the tolerability of CBDA in locomotor activity, motor coordination and muscular strength tests, and additionally for ability to modulate feeding behaviours. Methods: Male Lister hooded rats administered CBDA (0.05-5 mg/kg; p.o.) were assessed in habituated open field (for locomotor activity), static beam and grip strength tests. A further study investigated whether these CBDA doses modulated normal feeding behaviour. Finally, evidence of anxiolytic-like effects in the habituated open field prompted testing of 5 mg/kg CBDA for anxiolytic-like activity in unhabituated open field, light/dark box and novelty-supressed feeding (NSF) tests. Results: CBDA had no adverse effects upon performance in any neuromotor tolerability test, however anxiolytic-like behaviour was observed in the habituated open field. Normal feeding behaviours were unaffected by any dose. CBDA (5 mg/kg) abolished the increased feeding latency in the NSF test induced by the 5-HT1AR antagonist, WAY-100,635, indicative of anxiolytic-like effects, but had no effect on anxiety-like behaviour in the novel open field or light/dark box. Conclusions: CBDA is very well tolerated and devoid of the sedative side-effect profile of benzodiazepines, justifying its clinical investigation as a novel AN treatment

The Association of Antarctic Krill Euphausia superba with the Under-Ice Habitat

The association of Antarctic krill Euphausia superba with the under-ice habitat was investigated in the Lazarev Sea (Southern Ocean) during austral summer, autumn and winter. Data were obtained using novel Surface and Under Ice Trawls (SUIT), which sampled the 0–2 m surface layer both under sea ice and in open water. Average surface layer densities ranged between 0.8 individuals m−2 in summer and autumn, and 2.7 individuals m−2 in winter. In summer, under-ice densities of Antarctic krill were significantly higher than in open waters. In autumn, the opposite pattern was observed. Under winter sea ice, densities were often low, but repeatedly far exceeded summer and autumn maxima. Statistical models showed that during summer high densities of Antarctic krill in the 0–2 m layer were associated with high ice coverage and shallow mixed layer depths, among other factors. In autumn and winter, density was related to hydrographical parameters. Average under-ice densities from the 0–2 m layer were higher than corresponding values from the 0–200 m layer collected with Rectangular Midwater Trawls (RMT) in summer. In winter, under-ice densities far surpassed maximum 0–200 m densities on several occasions. This indicates that the importance of the ice-water interface layer may be under-estimated by the pelagic nets and sonars commonly used to estimate the population size of Antarctic krill for management purposes, due to their limited ability to sample this habitat. Our results provide evidence for an almost year-round association of Antarctic krill with the under-ice habitat, hundreds of kilometres into the ice-covered area of the Lazarev Sea. Local concentrations of postlarval Antarctic krill under winter sea ice suggest that sea ice biota are important for their winter survival. These findings emphasise the susceptibility of an ecological key species to changing sea ice habitats, suggesting potential ramifications on Antarctic ecosystems induced by climate change

Arterivirus Nsp1 Modulates the Accumulation of Minus-Strand Templates to Control the Relative Abundance of Viral mRNAs

The gene expression of plus-strand RNA viruses with a polycistronic genome depends on translation and replication of the genomic mRNA, as well as synthesis of subgenomic (sg) mRNAs. Arteriviruses and coronaviruses, distantly related members of the nidovirus order, employ a unique mechanism of discontinuous minus-strand RNA synthesis to generate subgenome-length templates for the synthesis of a nested set of sg mRNAs. Non-structural protein 1 (nsp1) of the arterivirus equine arteritis virus (EAV), a multifunctional regulator of viral RNA synthesis and virion biogenesis, was previously implicated in controlling the balance between genome replication and sg mRNA synthesis. Here, we employed reverse and forward genetics to gain insight into the multiple regulatory roles of nsp1. Our analysis revealed that the relative abundance of viral mRNAs is tightly controlled by an intricate network of interactions involving all nsp1 subdomains. Distinct nsp1 mutations affected the quantitative balance among viral mRNA species, and our data implicate nsp1 in controlling the accumulation of full-length and subgenome-length minus-strand templates for viral mRNA synthesis. The moderate differential changes in viral mRNA abundance of nsp1 mutants resulted in similarly altered viral protein levels, but progeny virus yields were greatly reduced. Pseudorevertant analysis provided compelling genetic evidence that balanced EAV mRNA accumulation is critical for efficient virus production. This first report on protein-mediated, mRNA-specific control of nidovirus RNA synthesis reveals the existence of an integral control mechanism to fine-tune replication, sg mRNA synthesis, and virus production, and establishes a major role for nsp1 in coordinating the arterivirus replicative cycle

Faith-based Institutions as Venues for Obesity Prevention

Purpose of review: To critique the scope and value of recent studies with a focus on obesity-related health promotion in faith organizations. Recent findings: Electronic database searches, scanning of the reference lists of identified articles, and hand searching of journals for articles written in English and published in 2013-16, revealed 16 studies. Half of the studies involved African-Americans, in churches and with predominantly female participants. Research among other ethnic groups was more likely to be exploratory. All of the 11 studies reporting the impact of programs on weight-related measures showed favourable outcomes. However due to study limitations (small sample size; short duration; attrition), significant unbiased effects cannot yet be concluded for most of the interventions reviewed. Study strengths included application of theory in community engagement, and detailed description of cultural tailoring. Summary: Faith organizations show promise as settings for obesity prevention among high-risk groups, particularly African-Americans. Support for progressing formative work to adequately powered, randomized controlled trials is vital. Wider involvement of diverse faith settings, and targeting obesity in men and childhood, would be valuable developments

Indicators of river system hydromorphological character and dynamics: understanding current conditions and guiding sustainable river management

The work leading to this paper received funding from the EU’s FP7 programme under Grant Agreement No. 282656 (REFORM). The Indicators were developed within the context of REFORM deliverable D2.1, therefore all partners involved in this deliverable contributed to some extent to their discussion and development

Super-Aggregations of Krill and Humpback Whales in Wilhelmina Bay, Antarctic Peninsula

Ecological relationships of krill and whales have not been explored in the Western Antarctic Peninsula (WAP), and have only rarely been studied elsewhere in the Southern Ocean. In the austral autumn we observed an extremely high density (5.1 whales per km2) of humpback whales (Megaptera novaeangliae) feeding on a super-aggregation of Antarctic krill (Euphausia superba) in Wilhelmina Bay. The krill biomass was approximately 2 million tons, distributed over an area of 100 km2 at densities of up to 2000 individuals m−3; reports of such ‘super-aggregations’ of krill have been absent in the scientific literature for >20 years. Retentive circulation patterns in the Bay entrained phytoplankton and meso-zooplankton that were grazed by the krill. Tagged whales rested during daylight hours and fed intensively throughout the night as krill migrated toward the surface. We infer that the previously unstudied WAP embayments are important foraging areas for whales during autumn and, furthermore, that meso-scale variation in the distribution of whales and their prey are important features of this system. Recent decreases in the abundance of Antarctic krill around the WAP have been linked to reductions in sea ice, mediated by rapid climate change in this area. At the same time, baleen whale populations in the Southern Ocean, which feed primarily on krill, are recovering from past exploitation. Consideration of these features and the effects of climate change on krill dynamics are critical to managing both krill harvests and the recovery of baleen whales in the Southern Ocean

Extrinsic primary afferent signalling in the gut

Visceral sensory neurons activate reflex pathways that control gut function and also give rise to important sensations, such as fullness, bloating, nausea, discomfort, urgency and pain. Sensory neurons are organised into three distinct anatomical pathways to the central nervous system (vagal, thoracolumbar and lumbosacral). Although remarkable progress has been made in characterizing the roles of many ion channels, receptors and second messengers in visceral sensory neurons, the basic aim of understanding how many classes there are, and how they differ, has proven difficult to achieve. We suggest that just five structurally distinct types of sensory endings are present in the gut wall that account for essentially all of the primary afferent neurons in the three pathways. Each of these five major structural types of endings seems to show distinctive combinations of physiological responses. These types are: 'intraganglionic laminar' endings in myenteric ganglia; 'mucosal' endings located in the subepithelial layer; 'muscular–mucosal' afferents, with mechanosensitive endings close to the muscularis mucosae; 'intramuscular' endings, with endings within the smooth muscle layers; and 'vascular' afferents, with sensitive endings primarily on blood vessels. 'Silent' afferents might be a subset of inexcitable 'vascular' afferents, which can be switched on by inflammatory mediators. Extrinsic sensory neurons comprise an attractive focus for targeted therapeutic intervention in a range of gastrointestinal disorders.Australian National Health and Medical Research Counci