Essential Current Concepts in Stem Cell Biology

Stem cell (SC) biology is a pervasive transdisciplinary research field encompassing any level of life organization (from molecular to morphological), combining different types of techniques (spanning from cellular to molecular)....

Analysis of Synthetic and Natural Cannabinoids in the Forensic Field Applying High-Resolution Mass Spectrometry

Multidimensional challenges arise in the field of forensic chemistry and toxicology from the ongoing emergence of synthetic cannabinoids (SCs) as well as the increasing legalization and medicalization of Cannabis sativa (C. sativa). This work addresses these challenges from different angles under the application of state-of-the-art mass spectrometry. “Phase I In vitro Metabolic Profiling of the Synthetic Cannabinoid Receptor Agonists CUMYL-THPINACA and ADAMANTYL-THPINACA” (study I) investigated the in vitro metabolic fate of two SCs. As data on the metabolism of newly emerging SCs is typically scarce, in vitro metabolism studies are required for the identification of suitable screening targets. The implementation of an in silico assisted workflow aided identification and structure elucidation of metabolites. It was observed that both SCs are vastly metabolized. Suitable screening targets were proposed. Additionally, investigation of the involved cytochrome P450 (CYP) isoenzymes gave valuable information on potential metabolic drug-drug adverse reactions and the potential influence of CYP polymorphisms. “Adulteration of low-delta-9-tetrahydrocannabinol products with synthetic cannabinoids: Results from drug checking services” (study II) presents data gained on the phenomenon of low THC cannabis products adulterated with SCs. Since 2020, such products have been increasingly detected in Switzerland and various European countries. The drug user’s unawareness about the presence of SCs combined with the typically higher potencies of SCs when compared to Δ9-tetrahydrocannabinol (THC) raised public health concerns. Cannabis samples and data on the drugs’ effects obtained from three drug checking services were investigated. A comprehensive screening method for SCs applying high resolution mass spectrometry (HRMS) was developed and validated. The carrier material was characterized regarding its THC and cannabidiol (CBD) contents. Data obtained from drug checking services included user self-reports on adverse effects after consumption of the respective adulterated and non-adulterated cannabis products. Increased risks for adverse effects, in particular cardiovascular and psychologic adverse effects, were found for products containing SCs when compared to regular cannabis products. The role of drug checking services as market monitoring tool and as source on effects of newly emerging new psychoactive substances (NPS) was highlighted. “Beyond Δ9-tetrahydrocannabinol and cannabidiol: Chemical differentiation of cannabis varieties applying targeted and untargeted analysis” (study III) presents the development and validation of a comprehensive analytical method for the determination of major and minor cannabinoids in cannabis inflorescences. Minor cannabinoids are gaining interest for various applications, ranging from improved product characterization and differentiation of cannabis varieties to bioanalytical questions in the medico-legal field. Samples derived from 18 cannabis varieties grown and stored under standardized conditions were characterized, applying the targeted and untargeted analyses using HRMS. Multivariate statistics, e.g., principal component analysis, were conducted to investigate similarities and differences between varieties. The presented methods allowed for a refined representation of chemical differences, i.e., chemical fingerprints, between varieties, expanding traditionally applied classification systems based on THC and CBD alone

Cell Migration - Methods and Protocols

As the title suggests, this book presents several techniques to study cells migration in vivo, in vitro, ex vivo and with different model systems to dissect many of the biochemical and biophysical properties (at both molecular and cellular levels) involved in the dynamics of migration and cell-to-cell communication..

Mouse oocyte development - Methods and Protocols

The Springer Protocols series “Methods in Molecular Biology” has published its 1818th volume which is entirely devoted to the development of the female gamete: the oocyte.

Cytoplasmic lattices are not linked to mouse 2-cell embryos developmental arrest

Cytoplasmic lattices are important regulators of oocyte maturation. They store components of the protein synthesis machinery including ribosomes and, among others, they are involved in the regulation of microtubule dynamics in both mouse and human. Cytoplasmic lattices undergo dramatic reorganizations at crucial stages of oocyte maturation, where they are abundantly present in the cytoplasm of developmentally competent oocytes named SN (Surrounded Nucleolus) while they are rare in the cytoplasm of 2-cell stage-arresting NSN (Not Surrounded Nucleolus) oocytes, suggestive of a requirement of cytoplasmic lattices for development past the 2-cell stage. Here, to elucidate this requirement, 2-cell mouse embryos derived from SN and NSN oocytes were analyzed by transmission electron microscopy. Contrary to what had been proposed hitherto, cytoplasmic lattices are present in 2-cell embryos derived not only from SN, but also from NSN oocytes, irrespective of the embryo production system (intra cytoplasmic sperm injection, parthenogenesis). Hence our conclusion that cytoplasmic lattices do not count among the factor(s) responsible for the embryo arrest at this crucial stage of development

Phase I In Vitro Metabolic Profiling of the Synthetic Cannabinoid Receptor Agonists CUMYL-THPINACA and ADAMANTYL-THPINACA

Synthetic cannabinoid receptor agonists (SCRAs) remain popular drugs of abuse. As many SCRAs are known to be mostly metabolized, in vitro phase I metabolic profiling was conducted of the two indazole-3-carboxamide SCRAs: CUMYL-THPINACA and ADAMANTYL-THPINACA. Both compounds were incubated using pooled human liver microsomes. The sample clean-up consisted of solid phase extraction, followed by analysis using liquid chromatography coupled to a high resolution mass spectrometer. In silico-assisted metabolite identification and structure elucidation with the data-mining software Compound Discoverer was applied. Overall, 28 metabolites were detected for CUMYL-THPINACA and 13 metabolites for ADAMATYL-THPINACA. Various mono-, di-, and tri-hydroxylated metabolites were detected. For each SCRA, an abundant and characteristic di-hydroxylated metabolite was identified as a possible in vivo biomarker for screening methods. Metabolizing cytochrome P450 isoenzymes were investigated via incubation of relevant recombinant liver enzymes. The involvement of mainly CYP3A4 and CYP3A5 in the metabolism of both substances were noted, and for CUMYL-THPINACA the additional involvement (to a lesser extent) of CYP2C8, CYP2C9, and CYP2C19 was observed. The results suggest that ADAMANTYL-THPINACA might be more prone to metabolic drug−drug interactions than CUMYL-THPINACA, when co-administrated with strong CYP3A4 inhibitors

Language resources for Italian: Towards the development of a corpus of annotated Italian multiword expressions

Napoli, Italy, December 5-7, 2016This paper describes the first resource annotated for multiword expressions (MWEs) in Italian. Two versions of this dataset have been prepared: the first with a fast markup list of out-of-context MWEs, and the second with an in-context annotation, where the MWEs are entered with their contexts. The paper also discusses annotation issues and reports the inter-annotator agreement for both types of annotations. Finally, the results of the first exploitation of the new resource, namely the automatic extraction of Italian MWEs, are presented

Desiderare di cambiare rotta

The origin of the COVID-19 pandemic is undoubtedly due to the devastation and destruction of the planet. From the industrial revolution onwards, we, sapiens sapiens, have devastated more than 2/3 of the earth's surface for industrialization, urbanization, and agricultural production processes. Not only that, we have deforested the equivalent of the surface of the African continent for the intensive breeding of cattle and the production of red meat. All this has dramatically expanded social and environmental inequalities and injustices. The report by Sir Partha Dasgupta (the economics of biodiversity) and the study of Gilbert Simodon, which we comment on here, are a precious help in making us responsible for the seriousness of the 'ecological question.' Are we behaving like good ancestors? And most importantly, what kind of planet will we leave for generations to come?    L’origine della pandemia da COVID-19 è da attribuire alla devastazione e distruzione del pianeta causata dai nostri esasperati consumi e stili di vita. Infatti è dalla rivoluzione industriale in poi che noi, sapiens sapiens, abbiamo devastato più dei 2/3 della superfice terrestre per processi di industrializzazione, urbanizzazione e produzione agricola. Non solo, abbiamo deforestato l’equivalente della superficie del continente africano per l’allevamento intensivo di bovini e la produzione di carne rossa.Tutto ciò ha ampliato a dismisura disuguaglianze ed ingiustizie sociali ed ambientali. Il rapporto di Sir Partha Dasgupta (l’economia della biodiversità) e lo studio dell’opera di Gilbert Simodon, che qui commentiamo, sono un prezioso aiuto per responsabilizzarci sulla gravità della ‘questione ecologica’. Ci stiamo comportando da buoni antenati? E, soprattutto, che tipo di pianeta lasceremo alle generazioni a venire? &nbsp