Sequential curing of thiol-acetoacetate-acrylate thermosets by latent Michael addition reactions

Thiol-acetoacetate-acrylate ternary dual-curing thermosets were prepared by a sequential process consisting of thiol-Michael addition to acrylates at room temperature followed by Michael addition of acetoacetates to acrylates at moderately elevated temperature. The curing sequence can be controlled with the help of the different acidities of the protons on thiol and acetoacetate groups, the favorable pKa of the base used as catalyst and the self-limiting character of Michael additions. The latency of the curing steps can be regulated by selection of the right catalysts, temperature and curing conditions. The properties of the intermediate and final materials can be tuned by changing the structure of the monomers and the contribution of both Michael addition reactions.Postprint (author's final draft

Higginsianins A and B, two fungal diterpenoid α-pyrones with cytotoxic activity against human cancer cells

Two new diterpenoid α-pyrones, named higginsianins A and B, were isolated from the mycelium of the microbial fungus Colletotrichum higginsianum grown in liquid culture. In previous studies, we have shown that both compounds reduce viability of different types of cancer cells in culture. Here, we extend our previous observations and explore, at a deeper level, the cellular effects of higginsianins treatment. Higginisianins A and B reduce viability of A431, HeLa and H1299 cancer cells. Both compounds increase the level of the cell cycle inhibitor p21WAF and reduce the rate of cell proliferation. Cell cycle analyses reveal that higginsianins arrest cancer cells in S-phase. Furthermore, cells incubated with higginsianins reveal discrete γ-H2AX positive nuclear foci indicating the occurrence of DNA lesions. At longer incubation times, higginsianins induce massive cell detachment and non-apoptotic cell death. Human primary keratinocytes and spontaneously immortalized Hacat cells, a preneoplastic cell line model, are less sensitive to higginsianins effects. These findings suggest that higginsianins exhibit considerable cytotoxicity against a wide spectrum of malignant cells and may be considered as promising anticancer agents

Prilog poznavanju kseno-raznolikosti životinja duž obale Kalabrije (južna Italija, srednji Mediteran)

In this paper a contribution to the knowledge of marine and brackish water alien species recorded along the Calabrian coasts (Southern Italy, Central Mediterranean) during the period 2000-2013 is given. The study area is located in the center of the Mediterranean. Records of alien species come from 13 years of both field and opportunistic fishing surveys. Also a bibliographical search in the scientific literature and public and private archives was performed. Eighteen of marine alien species recorded: 1 cnidarian, 11 molluscs, 3 crustaceans, and 4 bony fishes; in addition to these, was considered also the presence of four bony fish, that have naturally spread into the Mediterranean: Sphoeroides pachygaster, Gymnothorax moringa, Pseunes pellucidus and Zenopsis conchifera. The highest number of records comes from the Messina Strait. The most common and widest observed species were Percnon gibbesi, Callinectes sapidus, Fistularia commersonii and Procambarus clarckii. The record of Ruditapes philippinarum in the Foce Crati is the first for the Ionian Sea and for the Central Mediterranean. Gymnothorax moringa is here recorded for the first time in the Mediterranean.Ovaj rad predstavlja prilog poznavanju stranih vrsta pronađenih u morskoj i boćatoj vodi duž Kalabrijske obale (južna Italija, Središnji Mediteran) u razdoblju od 2000. do 2013. godine. Područje istraživanja se nalazi u središtu Mediterana. Evidencija stranih vrsta je proizišla iz 13 godina terenskog rada i oportunističkih istraživanja. Također su izvršena bibliografska pretraživanja u znanstvenoj literaturi u javnim i privatnim arhivima. Ukupno je zabilježeno 18 morskih stranih vrsta: 1 cnidaria, 11 mekušaca, 3 raka i 4 ribe koštunjače koje su se prirodno proširile u Mediteranu: Sphoeroides pachygaster, Gymnothorax moringa, Pseunes pellucidus i Zenopsis conchifera. Najveći broj nalaza dolazi iz Mesinskog tjesnaca. Najčešće i najšire promatrane vrste su Percnon gibbesi, Callinectes sapidus, Fistularia commersonii i Procambarus clarkii. Zapis o nalazu vrste Ruditapes philippinarum, kod mjesta Foce Crati, je prvi za Jonsko more i središnji Mediteran. Gymnothorax moringaje po prvi put zabilježena u Mediteranu

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre