Depicting the tree of life: The philosophical and historical roots of evolutionary tree diagrams

info:eu-repo/semantics/publishedVersio

The impact of transposable element activity on therapeutically relevant human stem cells

Human stem cells harbor significant potential for basic and clinical translational research as well as regenerative medicine. Currently ~ 3000 adult and ~ 30 pluripotent stem cell-based, interventional clinical trials are ongoing worldwide, and numbers are increasing continuously. Although stem cells are promising cell sources to treat a wide range of human diseases, there are also concerns regarding potential risks associated with their clinical use, including genomic instability and tumorigenesis concerns. Thus, a deeper understanding of the factors and molecular mechanisms contributing to stem cell genome stability are a prerequisite to harnessing their therapeutic potential for degenerative diseases. Chemical and physical factors are known to influence the stability of stem cell genomes, together with random mutations and Copy Number Variants (CNVs) that accumulated in cultured human stem cells. Here we review the activity of endogenous transposable elements (TEs) in human multipotent and pluripotent stem cells, and the consequences of their mobility for genomic integrity and host gene expression. We describe transcriptional and post-transcriptional mechanisms antagonizing the spread of TEs in the human genome, and highlight those that are more prevalent in multipotent and pluripotent stem cells. Notably, TEs do not only represent a source of mutations/CNVs in genomes, but are also often harnessed as tools to engineer the stem cell genome; thus, we also describe and discuss the most widely applied transposon-based tools and highlight the most relevant areas of their biomedical applications in stem cells. Taken together, this review will contribute to the assessment of the risk that endogenous TE activity and the application of genetically engineered TEs constitute for the biosafety of stem cells to be used for substitutive and regenerative cell therapiesS.R.H. and P.T.R. are funded by the Government of Spain (MINECO, RYC-2016- 21395 and SAF2015–71589-P [S.R.H.]; PEJ-2014-A-31985 and SAF2015–71589- P [P.T.R.]). GGS is supported by a grant from the Ministry of Health of the Federal Republic of Germany (FKZ2518FSB403)

Inflammatory cutaneous lesions in inflammatory bowel disease treated with Vedolizumab or Ustekinumab: an ECCO CONFER multicentre case series

This was a multicentre case series supported by the European Crohn's and Colitis Organisation (ECCO) and, performed as part of the Collaborative Network of Exceptionally Rare case reports (CONFER) project. The aim was to report on whether cutaneous lesions associated with inflammatory bowel disease (IBD) and refractory to standard medical therapy including anti-TNFs, would respond to the newer biologic agents Ustekinumab (UST) or Vedolizumab (VDZ). This report includes 28 patients with cutaneous lesions form 14 centres, all of whom had failed immunomodulator and anti-TNF therapy. Metastatic Crohn's disease (MCD) was diagnosed in 10 patients: UST led to remission in 5 cases and partial response in 4 cases, with a single report of VDZ inducing remission. All cases of MCD treated with UST responded after the first or second dose, whilst the median time for the 5 cases that attained remission was 5 months. Pyoderma gangrenosum (PG) was diagnosed in 4 cases: 3 of these attained remission with UST (median time to remission 4 months) whilst one case did not respond to VDZ. There were 7 cases of erythema nodosum (EN): UST led to remission in 4 cases and partial response in 1 case whilst VDZ had partial response in 2 cases and non-response in 2 cases. There were 7 single cases of other inflammatory lesions. In summary, UST appears to be useful for different cutaneous lesions including MCD, PG and EN, whilst VDZ does not appear to be useful for lesions that are independent of disease activity

Aviocentury (the 100th release selected by Christian Temporale)

Avioground is proudly to present Aviocentury Various Artists, the 100th label's release that includes 30 exclusive anthems of big names like Carmelo Carone, Cristian Paduraru, Roberto Carbonero, Greg Goldsack, Feedback, Ivan Enot, DJ Ralmm, Dos Rumanos, Ilya Mosolov, Ecco & many more, selected by our brother & evergreen top Italian dj Christian Temporale