Supplementary material for the article: Popovic, M.; Mazzega, E.; Toffoletto, B.; de Marco, A. Isolation of Anti-Extra-Cellular Vesicle Single-Domain Antibodies by Direct Panning on Vesicle-Enriched Fractions. Microbial cell factories 2018, 17 (1), 6. https://doi.org/10.1186/s12934-017-0856-9

Supplementary material for: [https://doi.org/10.1186/s12934-017-0856-9]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2069

Cardiac stem cell aging and heart failure

A side effect of the medical improvements of the last centuries is the progressive aging of the world population, which is estimated to reach the impressive number of 2 billion people with more than 65 years by 2050. As a consequence, age-related diseases, such as heart failure, will affect more and more patients in the next years. To understand the biological bases of these diseases will be a crucial task in order to find better treatments, and possibly slow age-related morbidity and mortality. Cardiac stem cells have been at the center of a heated debate and their potential involvement in cardiac homeostasis has been questioned. In this review, we summarize evidence obtained by independent groups, on different animal models and humans, that strongly support the important role played by immature, cardiac resident cells in the cardioprotection against heart failure

Transformative governance for ocean biodiversity

This Chapter analyzes the major underlying causes of marine biodiversity loss and focuses specifically on the lessons learnt for transformative ocean governance in the context of area-based management and spatial planning. It illustrates the broad recognition of the vital need for integrative, anticipatory, adaptive and inclusive governance of ocean biodiversity. Fundamentally, however, the Chapter underscores the need for transdisciplinary governance in supporting integration, inclusion and learning in ocean affairs for transformative change. An alternative governance approach is proposed: building on the inter-dependencies between human rights and marine biodiversity, a broader approach to fair and equitable benefit-sharing can support institutionalized shifts towards more transdisciplinary, integrative, inclusive and adaptive governance for the ocean at different scales

Transformative governance for ocean biodiversity

The ocean’s enormity and depth are illustrated by the limited ability of humankind to comprehend it. The current science and policy seascape remains largely fragmented, and as a result the integrity of marine life and the well-being of those (human and nonhuman) dependent on a healthy ocean is being negatively impacted. Fragmented governance is an indirect driver of ocean biodiversity loss due to its inability to provide synergistic solutions to address simultaneously multiple direct drivers for such loss (overfishing, land-based and marine pollution, and climate change). This governance problem is well known (Kelly et al., 2019; Watson-Wright and Valdés, 2018), and to some extent it is being addressed in ongoing international negotiations on an international instrument on marine biodiversity of areas beyond national jurisdiction (A/RES/72/249, 2017)

Development and Validation of a High- Performance Liquid Chromatography– Tandem Mass Spectrometry Method for the Simultaneous Determination of Irinotecan and Its Main Metabolites in Human Plasma and Its Application in a Clinical Pharmacokinetic Study

Irinotecan is currently used in several cancer regimens mainly in colorectal cancer (CRC). This drug has a narrow therapeutic range and treatment can lead to side effects, mainly neutropenia and diarrhea, frequently requiring discontinuing or lowering the drug dose. A wide inter-individual variability in irinotecan pharmacokinetic parameters and pharmacodynamics has been reported and associated to patients’ genetic background. In particular, a polymorphism in the UGT1A1 gene (UGT1A1*28) has been linked to an impaired detoxification of SN-38 (irinotecan active metabolite) to SN-38 glucuronide (SN-38G) leading to increased toxicities. Therefore, therapeutic drug monitoring of irinotecan, SN-38 and SN-38G is recommended to personalize therapy. In order to quantify simultaneously irinotecan and its main metabolites in patients’ plasma, we developed and validated a new, sensitive and specific HPLC–MS/MS method applicable to all irinotecan dosages used in clinic. This method required a small plasma volume, addition of camptothecin as internal standard and simple protein precipitation. Chromatographic separation was done on a Gemini C18 column (3 μM, 100 mm x 2.0 mm) using 0.1% acetic acid/bidistilled water and 0.1% acetic acid/acetonitrile as mobile phases. The mass spectrometer worked with electrospray ionization in positive ion mode and selected reaction monitoring. The standard curves were linear (R20.9962) over the concentration ranges (10–10000 ng/mL for irinotecan, 1–500 ng/mL for SN-38 and SN-38G and 1–5000 ng/mL for APC) and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy, determined on three quality control levels for all the analytes, were always <12.3% and between 89.4% and 113.0%, respectively. Moreover, we evaluated this bioanalytical method by re-analysis of incurred samples as an additional measure of assay reproducibility. This method wassuccessfully applied to a pharmacokinetic study in metastatic CRC patients enrolled in a genotype-guided phase Ib study of irinotecan administered in combination with 5-fluorouracil/ leucovorin and bevacizumab