Cannabis Users Show Enhanced Expression of CB<Subscript>1</Subscript>-5HT<Subscript>2A</Subscript> Receptor Heteromers in Olfactory Neuroepithelium Cells

Cannabinoid CB1 receptors (CB₁R) and serotonergic 2A receptors (5HT_2AR) form heteromers in the brain of mice where they mediate the cognitive deficits produced by delta-9-tetrahydrocannabinol. However, it is still unknown whether the expression of this heterodimer is modulated by chronic cannabis use in humans. In this study, we investigated the expression levels and functionality of CB₁R-5HT_2AR heteromers in human olfactory neuroepithelium (ON) cells of cannabis users and control subjects, and determined their molecular characteristics through adenylate cyclase and the ERK 1/2 pathway signaling studies. We also assessed whether heteromer expression levels correlated with cannabis consumption and cognitive performance in neuropsychological tests. ON cells from controls and cannabis users expressed neuronal markers such as βIII-tubulin and nestin, displayed similar expression levels of genes related to cellular self-renewal, stem cell differentiation, and generation of neural crest cells, and showed comparable Na⁺ currents in patch clamp recordings. Interestingly, CB₁R-5HT_2AR heteromer expression was significantly increased in cannabis users and positively correlated with the amount of cannabis consumed, and negatively with age of onset of cannabis use. In addition, a negative correlation was found between heteromer expression levels and attention and working memory performance in cannabis users and control subjects. Our findings suggest that cannabis consumption regulates the formation of CB₁R-5HT_2AR heteromers, and may have a key role in cognitive processing. These heterodimers could be potential new targets to develop treatment alternatives for cognitive impairments.     

A novel indicator of karyotype evolution in the tribe Leucocoryneae (Allioideae,Amaryllidaceae)

Journal of Plant Research - The tribe Leucocoryneae is taxonomically and cytogenetically complex, mainly due to its extraordinary morphological and karyological variation. Robertsonian...     

It's a long way to the top: Plant species diversity in the transition from managed to old‐growth forests

Questions

Do vascular plant species richness and beta‐diversity differ between managed and structurally complex unmanaged stands? To what extent do species richness and beta‐diversity relate to forest structural attributes and heterogeneity?

Location

Five national parks in central and southern Italy.

Methods

We sampled vascular plant species composition and forest structural attributes in eight unmanaged temperate mesic forest stands dominated or co‐dominated by beech, and in eight comparison stands managed as high forests with similar environmental features. We compared plant species richness, composition and beta‐diversity across pairs of stands (unmanaged vs managed) using GLMM s. Beta‐diversity was quantified both at the scale of each pair of stands using plot‐to‐plot dissimilarity matrices (species turnover), and across the whole data set, considering the distance in the multivariate species space of individual plots from their centroid within the same stand (compositional heterogeneity). We modelled the relationship between species diversity (richness and beta‐diversity) and forest structural heterogeneity and individual structural variables using GLMM s and multiple regression on distance matrices.

Results

Species composition differed significantly between managed and unmanaged stands, but not richness and beta‐diversity. We found weak evidence that plant species richness increased with increasing levels of structural heterogeneity and canopy diversification. At the scale of individual stands, species turnover was explained by different variables in distinct stands, with variables related to deadwood quantity and quality being selected most often. We did not find support for the hypothesis that compositional heterogeneity varies as a function of forest structural characteristics at the scale of the whole data set.

Conclusions

Structurally complex unmanaged stands have a distinct herb layer species composition from that of mature stands in similar environmental conditions. Nevertheless, we did not find significantly higher levels of vascular plant species richness and beta‐diversity in unmanaged stands. Beta‐diversity was related to patterns of deadwood accumulation, while for species richness the evidence that it increases with increasing levels of canopy diversification was weak. These results suggest that emulating natural disturbance, and favouring deadwood accumulation and canopy diversification may benefit some, but not all, facets of plant species diversity in Apennine beech forests.

     

Functional outcome of B cell activation by chromatin immune complex engagement of the B cell receptor and TLR9

We have previously shown that rheumatoid factors produced by Fas-deficient autoimmune-prone mice typically bind autologous IgG2a with remarkably low affinity. Nevertheless, B cells representative of this rheumatoid factor population proliferate vigorously in response to IgG2a/chromatin immune complexes through a mechanism dependent on the sequential engagement of the BCR and TLR9. To more precisely address the role of both receptors in this response, we analyzed the signaling pathways activated in AM14 B cells stimulated with these complexes. We found that the BCR not only serves to direct the chromatin complex to an internal compartment where it can engage TLR9 but also transmits a suboptimal signal that in combination with the signals emanating from TLR9 leads to NF-kappaB activation and proliferation. Importantly, engagement of both receptors leads to the up-regulation of a group of gene products, not induced by the BCR or TLR9 alone, that include IL-2. These data indicate that autoreactive B cells, stimulated by a combination of BCR and TLR9 ligands, acquire functional properties that may contribute to the activation of additional cells involved in the autoimmune disease process.     

Abundance drives broad patterns of generalisation in plant–hummingbird pollination networks

Abundant pollinators are often more generalised than rare pollinators. This could be because abundant species have more chance encounters with potential interaction partners. On the other hand, generalised species could have a competitive advantage over specialists, leading to higher abundance. Determining the direction of the abundance–generalisation relationship is therefore a ‘chicken‐and‐egg’ dilemma. Here we determine the direction of the relationship between abundance and generalisation in plant–hummingbird pollination networks across the Americas. We find evidence that hummingbird pollinators are generalised because they are abundant, and little evidence that hummingbirds are abundant because they are generalised. Additionally, most patterns of species‐level abundance and generalisation were well explained by a null model that assumed interaction neutrality (interaction probabilities defined by species relative abundances). These results suggest that neutral processes play a key role in driving broad patterns of generalisation in animal pollinators across large spatial scales.     

LRP1 promotes synthetic phenotype of pulmonary artery smooth muscle cells in pulmonary hypertension

Pulmonary hypertension (PH) is characterized by a thickening of the distal pulmonary arteries caused by medial hypertrophy, intimal proliferation and vascular fibrosis. Low density lipoprotein receptor-related protein 1 (LRP1) maintains vascular homeostasis by mediating endocytosis of numerous ligands and by initiating and regulating signaling pathways.Here, we demonstrate the increased levels of LRP1 protein in the lungs of idiopathic pulmonary arterial hypertension (IPAH) patients, hypoxia-exposed mice, and monocrotaline-treated rats. Platelet-derived growth factor (PDGF)-BB upregulated LRP1 expression in pulmonary artery smooth muscle cells (PASMC). This effect was reversed by the PDGF-BB neutralizing antibody or the PDGF receptor antagonist. Depletion of LRP1 decreased proliferation of donor and IPAH PASMC in a β1-integrin-dependent manner. Furthermore, LRP1 silencing attenuated the expression of fibronectin and collagen I and increased the levels of α-smooth muscle actin and myocardin in donor, but not in IPAH, PASMC. In addition, smooth muscle cell (SMC)-specific LRP1 knockout augmented α-SMA expression in pulmonary vessels and reduced SMC proliferation in 3D ex vivo murine lung tissue cultures.In conclusion, our results indicate that LRP1 promotes the dedifferentiation of PASMC from a contractile to a synthetic phenotype thus suggesting its contribution to vascular remodeling in PH.     

Economic costs of invasive alien ants worldwide

Biological Invasions - Invasive ants are amongst the most destructive and widespread invaders across the globe; they can strongly alter invaded ecosystems and are responsible for the loss of native...     

Disentangling climatic and nest predator impact on reproductive output reveals adverse high-temperature effects regardless of helper number in an arid-region cooperative bird

Climate exerts a major influence on reproductive processes, and an understanding of the mechanisms involved and which factors might mitigate adverse weather is fundamental under the ongoing climate change. Here, we study how weather and nest predation influence reproductive output in a social species, and examine whether larger group sizes can mitigate the adverse effects of these factors. We used a 7-year nest predator-exclusion experiment on an arid-region cooperatively breeding bird, the sociable weaver. We found that dry and, especially, hot weather were major drivers of nestling mortality through their influence on nest predation. However, when we experimentally excluded nest predators, these conditions were still strongly associated with nestling mortality. Group size was unimportant against nest predation and, although positively associated with reproductive success, it did not mitigate the effects of adverse weather. Hence, cooperative breeding might have a limited capacity to mitigate extreme weather effects.