Design of a potent and selective dual JAK1/TYK2 inhibitor.

Janus kinase (JAK) inhibitors have gathered interest as treatments for several inflammatory and autoimmune diseases. The four first marketed inhibitors target JAK1, with varying selectivity towards other JAK family members, but none inhibit tyrosine kinase-2 (TYK2) at clinically relevant doses. TYK2 is required for the signaling of the interleukin (IL)-12 and IL-23 cytokines, which are key to the polarization of T1 and T17 cells, respectively; two cell subtypes that play major roles in inflammatory diseases.

The impact of extraction method and pollen concentration on community composition for pollen metabarcoding.

Premise: Plants and pollinators closely interact with each other to form complex networks of species interactions. Metabarcoding of pollen collections has recently been proposed as an advantageous method for the construction of such networks, but the extent to which diversity and community analyses depend on the extraction method and pollen concentration used remains unclear.

Methods: In this study, we used a dilution series of two pollen mixtures (a mock community and pooled natural pollen loads from bumblebees) to assess the effect of mechanical homogenization and two DNA extraction kits (spin column DNA extraction kit and magnetic bead DNA extraction kit) on the detected pollen richness and community composition.

Phenological mismatches mitigate the ecological impact of a biological invader on amphibian communities.

Horizon scans have emerged as a valuable tool to anticipate the incoming invasive alien species (IAS) by judging species on their potential impacts. However, little research has been conducted on quantifying actual impacts and assessing causes of species-specific vulnerabilities to particular IAS due to persistent methodological challenges. The underlying interspecific mechanisms driving species-specific vulnerabilities therefore remain poorly understood, even though they can substantially improve the accuracy of risk assessments.

Discovery of GLPG3667, a Selective ATP Competitive Tyrosine Kinase 2 Inhibitor for the Treatment of Autoimmune Diseases.

Tyrosine kinase 2 (TYK2) mediates cytokine signaling through type 1 interferon, interleukin (IL)-12/IL-23, and the IL-10 family. There appears to be an association between TYK2 genetic variants and inflammatory conditions, and clinical evidence suggests that selective inhibition of TYK2 could produce a unique therapeutic profile. Here, we describe the discovery of compound (GLPG3667), a reversible and selective TYK2 adenosine triphosphate competitive inhibitor in development for the treatment of inflammatory and autoimmune diseases.

Environmental DNA metabarcoding reflects spatiotemporal fish community shifts in the Scheldt estuary.

Estuarine ecosystems face increasing anthropogenic pressures, necessitating effective monitoring methods to mitigate their impacts on the biodiversity they harbour. The use of environmental DNA (eDNA) based detection methods is increasingly recognized as a promising tool to complement other, potentially invasive monitoring techniques. Integrating such eDNA analyses into monitoring frameworks for large ecosystems is still challenging and requires a deeper understanding of the scale and resolution at which eDNA patterns may offer insights in species presence and community composition space and time.