Proceedings of the EYCN Symposium – 1st Edition

The 1st edition of the EYCN Symposium is the scientific event organized by the Italian Chemical Society and the European Young Chemists’ Network within the XIII EYCN Delegate Assembly. This symposium is fully devoted to young researchers, such as MSc and PhD students, post-doc fellows and young researchers in companies. All the disciplines of Chemistry are covered: analytical, physical, industrial, organic, inorganic, theoretical, pharmaceutical, biological, environmental, macromolecular and electrochemistry

Proceedings of the Merck & Elsevier Young Chemists Symposium (MEYCS 2018)

Dear participants, welcome to the 18th edition of the Merck & Elsevier Young Chemists Symposium, formerly SAYCS and MYCS. This conference is an international scientific event organized by the Young Group of the Italian Chemical Society (SCI Giovani) with the financial support of Merck and Elsevier. This symposium is fully devoted to young researchers, such as MSc and PhD students, post-doc fellows and young researchers in companies. All the disciplines of Chemistry are covered: analytical, physical, industrial, organic, inorganic, theoretical, pharmaceutical, biological, environmental, macromolecular and electrochemistry. This year, a special emphasis will be given to chemistry from knowledge to innovation: how chemistry is increasingly present in all of the fields that are essential for human life, and how chemical fundamentals are pushing novel technologies? This year we have the exceptional number of 212 participants; we thank you for the great trust shown towards SCI Giovani, Merck and Elsevier. Enjoy the conference

Rescue of secretion of rare-disease associated misfolded mutant glycoproteins in UGGT1 knock-out mammalian cells

Endoplasmic reticulum (ER) retention of misfolded glycoproteins is mediated by the ER-localised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). The enzyme recognises a misfolded glycoprotein and flags it for ER retention by re-glucosylating one of its N-linked glycans. In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease, even if the mutant glycoprotein retains activity (“responsive mutant”). Using confocal laser scanning microscopy, we investigated here the subcellular localisation of the human Trop-2-Q118E, E227K and L186P mutants, which cause gelatinous drop-like corneal dystrophy (GDLD). Compared with the wild type Trop-2, which is correctly localised at the plasma membrane, these Trop-2 mutants are retained in the ER. We studied fluorescent chimeras of the Trop-2 Q118E, E227K and L186P mutants in mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 genes. The membrane localisation of the Trop-2 Q118E, E227K and L186P mutants was successfully rescued in UGGT1-/- cells. UGGT1 also efficiently reglucosylated Trop-2-Q118E-EYFP in cellula. The study supports the hypothesis that UGGT1 modulation would constitute a novel therapeutic strategy for the treatment of pathological conditions associated to misfolded membrane glycoproteins (whenever the mutation impairs but does not abrogate function), and it encourages the testing of modulators of ER glycoprotein folding quality control as broad-spectrum rescue-of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants

Expression of distinct RNAs from 3′ untranslated regions

The 3′ untranslated regions (3′UTRs) of eukaryotic genes regulate mRNA stability, localization and translation. Here, we present evidence that large numbers of 3′UTRs in human, mouse and fly are also expressed separately from the associated protein-coding sequences to which they are normally linked, likely by post-transcriptional cleavage. Analysis of CAGE (capped analysis of gene expression), SAGE (serial analysis of gene expression) and cDNA libraries, as well as microarray expression profiles, demonstrate that the independent expression of 3′UTRs is a regulated and conserved genome-wide phenomenon. We characterize the expression of several 3′UTR-derived RNAs (uaRNAs) in detail in mouse embryos, showing by in situ hybridization that these transcripts are expressed in a cell- and subcellular-specific manner. Our results suggest that 3′UTR sequences can function not only in cis to regulate protein expression, but also intrinsically and independently in trans, likely as noncoding RNAs, a conclusion supported by a number of previous genetic studies. Our findings suggest novel functions for 3′UTRs, as well as caution in the use of 3′UTR sequence probes to analyze gene expression

The role of UDP-Glc:glycoprotein glucosyltransferase 1 in the maturation of an obligate substrate prosaposin

A natural substrate for UGT1 is confirmed, revealing how the enzyme functions in the calnexin chaperone system as a quality control step in protein folding

Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis

A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy