Y-box binding protein 1 (YB-1) relevance in estrogen receptor-positive (ER+) breast cancer

Tese de mestrado, Biologia Molecular e Genética, Universidade de Lisboa, Faculdade de Ciências, 2016

The end of chocolate box-style integration? EU-Swiss relations after the referendum. CEPS Commentaries, 28 February 2014

Surveying the landscape following the Swiss referendum on February 9th, Adam Łazowski observes that once Swiss voters are deprived of the benefits of the EU internal market, they may come to appreciate that their days of cherry-picking from among EU policies are over. This might present the EU with a golden opportunity to press for a comprehensive framework agreement with Switzerland that would simplify the existing regime and provide for a uniform institutional set-up. He concludes, however, that what both sides cannot avoid is a frank discussion about free movement of persons, noting that that dossier will be crucial for any future steps that will be taken by the EU and the Swiss authorities.

Screening of the Open Source Malaria Box Reveals an Early Lead Compound for the Treatment of Alveolar Echinococcosis.

The metacestode (larval) stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE), a very severe and in many cases incurable disease. To date, benzimidazoles such as albendazole and mebendazole are the only approved chemotherapeutical treatment options. Benzimidazoles inhibit metacestode proliferation, but do not act parasiticidal. Thus, benzimidazoles have to be taken a lifelong, can cause adverse side effects such as hepatotoxicity, and are ineffective in some patients. We here describe a newly developed screening cascade for the evaluation of the in vitro efficacy of new compounds that includes assessment of parasiticidal activity. The Malaria Box from Medicines for Malaria Venture (MMV), comprised of 400 commercially available chemicals that show in vitro activity against Plasmodium falciparum, was repurposed. Primary screening was carried out at 10 μM by employing the previously described PGI assay, and resulted in the identification of 24 compounds that caused physical damage in metacestodes. Seven out of these 24 drugs were also active at 1 μM. Dose-response assays revealed that only 2 compounds, namely MMV665807 and MMV665794, exhibited an EC50 value below 5 μM. Assessments using human foreskin fibroblasts and Reuber rat hepatoma cells showed that the salicylanilide MMV665807 was less toxic for these two mammalian cell lines than for metacestodes. The parasiticidal activity of MMV665807 was then confirmed using isolated germinal layer cell cultures as well as metacestode vesicles by employing viability assays, and its effect on metacestodes was morphologically evaluated by electron microscopy. However, both oral and intraperitoneal application of MMV665807 to mice experimentally infected with E. multilocularis metacestodes did not result in any reduction of the parasite load.

(Table 2) Radiocarbon ages on Arctic box and multicores

Paleo-sea-ice history in the Arctic Ocean was reconstructed using the sea-ice dwelling ostracode Acetabulastoma arcticum from late Quaternary sediments from the Mendeleyev, Lomonosov, and Gakkel Ridges, the Morris Jesup Rise and the Yermak Plateau. Results suggest intermittently high levels of perennial sea ice in the central Arctic Ocean during Marine Isotope Stage (MIS) 3 (25-45 ka), minimal sea ice during the last deglacial (16-11 ka) and early Holocene thermal maximum (11-5 ka) and increasing sea ice during the mid-to-late Holocene (5-0 ka). Sediment core records from the Iceland and Rockall Plateaus show that perennial sea ice existed in these regions only during glacial intervals MIS 2, 4, and 6. These results show that sea ice exhibits complex temporal and spatial variability during different climatic regimes and that the development of modern perennial sea ice may be a relatively recent phenomenon.

Abyssal community analysis from replicate box cores in the central North Pacific

A 0.25 m**2 United States Naval Electronics Laboratory box corer was used to take replicate samples from an oligotrophic bottom under the North Pacific Central Water Mass (~28°N, 155°W). The bottom is a red clay with manganese nodules at a depth of 5500-5800 m. Macrofaunal density ranges from 84 to 160 individuals per m**2 and is therefore much the same as in Northwest Atlantic Gyre waters. Of the macrofaunal taxa, polychaetes dominate (55 %), followed by tanaids (18 %), bivalves (7 %), and isopods (6 %). Meiofaunal taxa were only partially retained by the 297 µm screen used in washing. Even then, they are 1.5-3.9 times as abundant as the macrofaunal taxa, with nematodes being numerically dominant by far. Foraminifera seem to comprise an important portion of the community, but could not be assessed accurately because of the inability to discriminate living and dead tests. Remains of what are probably xenophyophoridans are also very important, but offer the same problem. Faunal diversity is extremely high, with deposit feeders comprising the overwhelming majority. Most species are rare, being encountered only once. The distributions of only three species show any significant deviation from randomness. The polychaete fauna from box cores collected from 90 miles to the north was not significantly different from that of the principal study locality. Concordance appeared at several taxonomic levels, from species through macrofaunal/meiofaunal relationships. As a result, the variation in total animal abundance shows aggregation among cores. We discuss Sokolova's concept of a deep-sea oligotrophic zone dominated by suspension feeders, and reconcile it with our present findings. The high diversity of the fauna combined with the low food level contradict theories that relate diversity directly with productivity.

Table 1. Radiocarbon dates from TPC522 and box core surface samples from BC521 and BC523

Recent intensification of wind-driven upwelling of warm upper circumpolar deep water (UCDW) has been linked to accelerated melting of West Antarctic ice shelves and glaciers. To better assess the long term relationship between UCDWupwelling and the stability of theWest Antarctic Ice Sheet, we present a multi-proxy reconstruction of surface and bottom water conditions in Marguerite Bay, West Antarctic Peninsula (WAP), through the Holocene. A combination of sedimentological, diatom and foraminiferal records are, for the first time, presented together to infer a decline in UCDW influence within Marguerite Bay through the early to mid Holocene and the dominance of cyclic forcing in the late Holocene. Extensive glacial melt, limited sea ice and enhanced primary productivity between 9.7 and 7.0 ka BP is considered to be most consistent with persistent incursions of UCDW through Marguerite Trough. From 7.0 ka BP sea ice seasons increased and productivity decreased, suggesting that UCDW influence within Marguerite Bay waned, coincident with the equatorward migration of the Southern Hemisphere Westerly Winds (SWW). UCDW influence continued through the mid Holocene, and by 4.2 ka BP lengthy sea ice seasons persisted within Marguerite Bay. Intermittent melting and reforming of this sea ice within the late Holocene may be indicative of episodic incursions of UCDW into Marguerite Bay during this period. The cyclical changes in the oceanography within Marguerite Bay during the late Holocene is consistent with enhanced sensitively to ENSO forcing as opposed to the SWW-forcing that appears to have dominated the early to mid Holocene. Current measurements of the oceanography of the WAP continental shelf suggest that the system has now returned to the early Holocene-like oceanographic configuration reported here, which in both cases has been associated with rapid deglaciation.