The European Lead Factory: Results from a decade of collaborative, public-private, drug discovery programs.

The European Lead Factory (ELF) is a consortium of universities and small and medium-sized enterprises (SMEs) dedicated to drug discovery, and the pharmaceutical industry. This unprecedented consortium provides high-throughput screening, triage, and hit validation, including to non-consortium members. The ELF library was created through a novel compound-sharing model between nine pharmaceutical companies and expanded through library synthesis by chemistry-specialized SMEs.

The development of the O-sensing system in an amphibious fish: consequences of variation in environmental O levels.

Proper development of the O-sensing system is essential for survival. Here, we characterized the development of the O-sensing system in the mangrove rivulus (Kryptolebias marmoratus), an amphibious fish that transitions between hypoxic aquatic environments and O-rich terrestrial environments. We found that NECs formed in the gills and skin of K.

Fluctuating environments during early development can limit adult phenotypic flexibility: insights from an amphibious fish.

The interaction between developmental plasticity and the capacity for reversible acclimation (phenotypic flexibility) is poorly understood, particularly in organisms exposed to fluctuating environments. We used an amphibious killifish () to test the hypotheses that organisms reared in fluctuating environments (i) will make no developmental changes to suit any one environment because fixing traits to suit one environment could be maladaptive for another, and (ii) will be highly phenotypically flexible as adults because their early life experiences predict high environmental variability in the future. We reared fish under constant (water) or fluctuating (water-air) environments until adulthood and assessed a suite of traits along the oxygen cascade (e.

Ageing impacts phenotypic flexibility in an air-acclimated amphibious fish.

The ability to tolerate environmental change may decline as fishes age. We tested the hypothesis that ageing influences the scope for phenotypic flexibility in the mangrove rivulus (Kryptolebias marmoratus), an amphibious fish that transitions between two vastly different environments, water and land. We found that older fish (4-6 years old) exhibited marked signs of ageing; older fish were reproductively senescent, had reduced fin regenerative capacity and body condition, and exhibited atrophy of both oxidative and glycolytic muscle fibers relative to younger adult fish (1-2 years old).

Hydrogen sulphide toxicity and the importance of amphibious behaviour in a mangrove fish inhabiting sulphide-rich habitats.

We investigated amphibious behaviour, hydrogen sulphide (HS) tolerance, and the mechanism of HS toxicity in the amphibious mangrove rivulus (Kryptolebias marmoratus). We found that fish emersed (left water) in response to acutely elevated [HS] (~ 130-200 µmol l). The emersion response to HS may be influenced by prior acclimation history due to acclimation-induced alterations in gill morphology and/or the density and size of neuroepithelial cells (NECs) on the gills and skin.