Interplay Between Endocannabinoid System and Neurodegeneration: Focus on Polypharmacology

Pharmacological treatment of complex pathologies, such as neurodegenerative diseases still represents a major challenge, due to the networked pathways involved in their onset and progression that may require equally complex therapeutic approaches. Polypharmacology, based on the simultaneous modulation of multiple targets involved in the disease, may offer the potential to increase effectiveness and reduce the drawbacks related to the use of drug combinations. Clearly, this approach requires both the knowledge of the systems responsible for disease development and the discovery of new attractive targets to be exploited to design a multitarget drug. Over the last years, an ever increasing interest has focused on the endocannabinoid system, implicated in the modulation of several physiological functions, among which neuroinflammation, a crucial process for most neurodegenerative diseases. In this respect, the cannabinoid receptor subtype 2 represents a promising therapeutic target, being overexpressed in microglia cells and thus involved in neuroinflammation. The indirect modulation of this system through the inhibition of the main enzymes responsible for endocannabinoids metabolism, namely fatty acid amide hydrolase and monoacylglycerol lipase, may also significantly affect neurodegenerative processes. The aim of this review is to give an overview of the opportunities posed by the endocannabinoid system for neurodegenerative diseases management, mainly focusing on the potential for a multitarget strategy

Flavonoid-inspired vascular disrupting agents: Exploring flavone-8-acetic acid and derivatives in the new century

Naturally occurring flavonoids are found as secondary metabolites in a wide number of plants exploited for both medicine and food and have long been known to be endowed with multiple biological activities, making them useful tools for the treatment of different pathologies. Due to the versatility of the scaffolds and the vast possibilities of appropriate decoration, they have also been regarded as fruitful sources of lead compounds and excellent chemical platforms for the development of bioactive synthetic compounds. Flavone-8-acetic acid (FAA) and 5,6-dimethylxanthone acetic acid (DMXAA) emerged for their antitumour potential due to the induction of cytokines and consequent rapid haemorrhagic necrosis of murine tumour vasculature, and different series of derivatives have been designed thereafter. Although the promising DMXAA failed in phase III clinical trials because of strict species-specificity, a boost in research came from the recent identification of the stimulator of interferon genes (STING), responsible for supporting tumoural innate immune responses, as a possible biological target. Consequently, in the last decade a renewal of interest for these flavonoid-based structures was noticed, and novel derivatives have been synthesised and evaluated for a deeper understanding of the molecular features needed for affecting human cells. Un-doubtedly, these natural-derived molecules deserve further investigation and still appear attractive in an anticancer perspective

Regular vs. classical M\"obius transformations of the quaternionic unit ball

The regular fractional transformations of the extended quaternionic space have been recently introduced as variants of the classical linear fractional transformations. These variants have the advantage of being included in the class of slice regular functions, introduced by Gentili and Struppa in 2006, so that they can be studied with the useful tools available in this theory. We first consider their general properties, then focus on the regular M\"obius transformations of the quaternionic unit ball B, comparing the latter with their classical analogs. In particular we study the relation between the regular M\"obius transformations and the Poincar\'e metric of B, which is preserved by the classical M\"obius transformations. Furthermore, we announce a result that is a quaternionic analog of the Schwarz-Pick lemma.Comment: 14 page

The impact of urbanisation on chipmunks, arboreal and flying squirrels: a global systematic review

The current, rapid urbanisation process impacts global biodiversity and can be a driver for phenotypic changes in mammals that persist in cities. Animals display different response strategies in urban environments compared to natural areas, but patterns may differ among species. To better comprehend this process, we focused on a limited number of species that are present in many urban green spaces around the globe.The aim of this systematic review is to investigate which response strategies chipmunks, arboreal and flying squirrels use to cope with urban environments, exploring whether there are general response patterns, and to reveal potential adaptations to life in urban areas. We included studies that compared trait differences among conspecifics living in different areas along an urbanisation gradient (rural-urban) and studies comparing individuals or populations between urban areas with different environmental characteristics.The effects of urbanisation on chipmunks, arboreal and flying squirrels, at the individual and at the population levels, were identified in nine topics. Included articles explored at least one of these topics and their key findings were described.Effects of urbanisation are evident in all considered topics. However, we found contrasting patterns between species or even among individuals of the same species studied in different geographical areas. Overall, we reported two knowledge gaps: some phenotypic traits were considered in few studies, and many species, especially those living in the Global South, where urban growth rate is higher, have not been studied.This systematic review suggests that urbanisation can be an important driver for adaptation in small mammals, underlining the complexity and differentiation of response patterns. Since target species have important ecological and social roles, additional comparative studies, increasing our understanding of processes that determine their presence in cities, are essential for urban green planning which aims to conserve biodiversity

Hide-and-seek in a highly human-dominated landscape: insights into movement patterns and selection of resting sites of rehabilitated wolves (Canis lupus) in Northern Italy

Assessing the behavioural responses of floating wolves to human presence is crucial for investigating the chance of wolf populations expanding into urbanised landscapes. We studied the movement ecology of three rehabilitated wolves in a highly human-dominated landscape (Po Plain, Italy) to explore wolf’s plasticity amid widespread human pressure. To reach this aim, we estimated individual 95% utilisation distributions (UD) after the release and inspected both 95% UDs and net squared displacements to identify individual movement patterns; tested for differences in movement patterns during day and night; and analysed the selection of resting sites during dispersal movement in a highly human-altered environment. Both the 95% UDs and step lengths were smaller for wolves settling in suitable areas than for those settling in more urbanised areas. All wolves exhibited strong temporal segregation with humans during all movement phases, particularly while dispersing across highly urbanised areas. Main roads and proximity to built-up areas were shown to limit wolves’ dispersal, whereas small-wooded patches that provide shelter during rest facilitated long-distance movements. This study provides important insights into wolf movement and settling in urban and peri-urban areas, providing critical knowledge to promote human–carnivore coexistenc

The advantage of living in the city: effects of urbanization on body size and mass of native and alien squirrels.

In an ever more urbanized world, animals have to cope with different challenging conditions that may shape the individual’s phenotype in the urban environment. Since body mass and body size are found to be related to fitness in many species, investigating the variation in these two morphological traits along the rural-urban gradient, is a first step to understand how animals adapt to urbanization. Here we studied two tree squirrels, the native Eurasian red squirrel (Sciurus vulgaris) and the invasive Eastern grey squirrel (Sciurus carolinensis), using a pseudo-experimental design with replicated study sites (2 rural, 2 suburban and 2 urban sites for each species). We investigated whether squirrels differed in body size and body mass along the urbanization gradient and whether the invasive alien squirrels had more marked differences along the gradient, showing a higher adaptation capacity. We did not find variation in body size in red squirrels along the gradient, but invasive grey squirrels were slightly larger in urban than in other area-types. In both species, animals of either sex were heavier in the urban than in the rural sites, while the difference between urban and suburban areas depends on species and sex. Hence, morphologically both native and invasive species showed similar changes, with higher body mass in urban habitat, which could result in higher fitness, since body mass in squirrels species is positively related to reproductive success

Propagation of piper hispidum through leaf cuttings.

Made available in DSpace on 2018-10-11T00:33:56Z (GMT). No. of bitstreams: 1 2018IJDRPiperhispidum.pdf: 353394 bytes, checksum: 7cb89d851e5614e7d10c0e28b5a9d2a0 (MD5) Previous issue date: 2018-10-10bitstream/item/184171/1/2018-IJDR-Piper-hispidum.pd

The strong and the hungry: Bias in capture methods for mountain hares (Lepus timidus).

Estimating density, age and sex structure of wild populations is a key objective in wildlife management. Live trapping is frequently used to collect data on populations of small and medium-sized mammals. Ideally, sampling mammal populations by live capturing of individuals provides a random and representative sample of the target population. Trapping data may, however, be biased. We used live-capture data from mountain hares Lepus timidus in Scotland to assess sampling bias between two different capture methods.Wecaptured hares using baited cage traps and long nets on five study areas in the Scottish Highlands. After controlling for the effects of body size, individuals caught in traps were lighter than individuals caught using long nets, suggesting that the body condition of hares differed between the capture methods. This tendency may reflect an increased risk-taking of individuals in poorer body condition and less aversion to entering traps in order to benefit from eating bait. Overall, we caught more adult hares than juveniles and more female hares than males. Our results show that estimates of density and population structure of mountain hares using livecapture data could be affected by the capture method used. We suggest that live-capture studies employ more than one capture method and test for heterogeneity in capture probability to minimise potential bias and achieve reliable estimates of population parameters

Regular Moebius transformations of the space of quaternions

Let H be the real algebra of quaternions. The notion of regular function of a quaternionic variable recently presented by G. Gentili and D. C. Struppa developed into a quite rich theory. Several properties of regular quaternionic functions are analogous to those of holomorphic functions of one complex variable, although the diversity of the quaternionic setting introduces new phenomena. This paper studies regular quaternionic transformations. We first find a quaternionic analog to the Casorati-Weierstrass theorem and prove that all regular injective functions from H to itself are affine. In particular, the group Aut(H) of biregular functions on H coincides with the group of regular affine transformations. Inspired by the classical quaternionic linear fractional transformations, we define the regular fractional transformations. We then show that each regular injective function from the Alexandroff compactification of H to itself is a regular fractional transformation. Finally, we study regular Moebius transformations, which map the unit ball B onto itself. All regular bijections from B to itself prove to be regular Moebius transformations.Comment: 12 page