Third-Generation CD73 Inhibitors Based on a 4,6-Disubstituted-2-Thiopyridine Scaffold.

Various series of 4,6-disubstituted-2-thiopyridine derivatives were synthesized and evaluated as potential ecto-5'-nucleotidase (CD73) inhibitors. Altogether, about ninety compounds were prepared using a general synthetic pathway involving one or two steps (eventually one-pot) procedures. Variation of the nature of the substituents in positions 4 and 6 (methyl, trifluoromethyl or phenyl) of the thiopurine ring, as well as on the thiol function, was examined and led to marked differences both in term of reactivity and ability to interfere with the putative target protein.

Summer primary production of Arctic kelp communities is more affected by duration than magnitude of simulated marine heatwaves.

Fjord systems in the Norwegian Arctic are experiencing an increasing frequency and magnitude of marine heatwaves. These episodic heat stress events can have varying degrees of acute impacts on primary production and nutrient uptake of mixed kelp communities, as well as modifying the biogeochemical cycling in nearshore systems where vast areas of kelp create structural habitat. To assess the impact of future marine heatwaves on kelp communities, we conducted a 23 day mesocosm experiment exposing mixed kelp communities to warming and heatwave scenarios projected for the year 2100.

How fiber bundle alterations differ in presumed LATE and amnestic Alzheimer's disease.

Introduction: Typical Alzheimer's disease (AD) and limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy (LATE) are two neurodegenerative diseases that present with a similar initial amnestic clinical phenotype but are associated with distinct proteinopathies.

Methods: We investigated white matter (WM) fiber bundle alterations, using fixel-based analysis, a state-of-the-art diffusion magnetic resonance imaging model, in early AD, presumed LATE, and controls. We also investigated regional cortical atrophy.

Productivity of mixed kelp communities in an Arctic fjord exhibit tolerance to a future climate.

Arctic fjords are considered to be one of the ecosystems changing most rapidly in response to climate change. In the Svalbard archipelago, fjords are experiencing a shift in environmental conditions due to the Atlantification of Arctic waters and the retreat of sea-terminating glaciers. These environmental changes are predicted to facilitate expansion of large, brown macroalgae, into new ice-free regions.