The acidic intrinsically disordered region of the inflammatory mediator HMGB1 mediates fuzzy interactions with CXCL12.

Chemokine heterodimers activate or dampen their cognate receptors during inflammation. The CXCL12 chemokine forms with the fully reduced (fr) alarmin HMGB1 a physiologically relevant heterocomplex (frHMGB1•CXCL12) that synergically promotes the inflammatory response elicited by the G-protein coupled receptor CXCR4. The molecular details of complex formation were still elusive. Here we show by an integrated structural approach that frHMGB1•CXCL12 is a fuzzy heterocomplex. Unlike previous assumptions, frHMGB1 and CXCL12 form a dynamic equimolar assembly, with structured and unstructured frHMGB1 regions recognizing the CXCL12 dimerization surface. We uncover an unexpected role of the acidic intrinsically disordered region (IDR) of HMGB1 in heterocomplex formation and its binding to CXCR4 on the cell surface. Our work shows that the interaction of frHMGB1 with CXCL12 diverges from the classical rigid heterophilic chemokines dimerization. Simultaneous interference with multiple interactions within frHMGB1•CXCL12 might offer pharmacological strategies against inflammatory conditions.

Molecular identification of Contracaecum rudolphii A and B (Nematoda: Anisakidae) from cormorants collected in a freshwater ecosystem of the pre-alpine area in Northern Italy.

Contracaecum rudolphii (s.l.) is a complex of sibling species with different genetic structure and ecological preference. This study reports the presence of specimens of Contracaecum rudolphii (s.l.) from sedentary and wintering cormorants (Phalacrocorax carbo sinensis) from the pre-mountain area of the Alps in Northern Italy, an important crossroads for most of the bird migration routes. A total of 48 specimens of cormorants collected from two adjacent freshwater habitats were analysed and C. rudolphii nematodes were retrieved in 100% of the examined specimens. A subsamples of 115 C. rudolphii individuals were genetically characterized and found to belong to the sibling species C. rudolphii B (n = 90) and C. rudolphii A (n = 25). C. rudolphii B were retrieved from both locations and included adults as well as larvae, while only adults of C. rudolphii A were detected, and in just one location. As expected for a freshwater environment, C. rudolphii B constitutes the largest sibling fraction, indicating that this likely is the endemic species, while cormorants originating from the breeding brackish lagoons and marine coastal environments of central and northern Europe could have brought C. rudolphii A from their breeding sites or migration stopovers.