Hajek, M. | Search bioRxiv

bioRxiv2024

A selective alternative pathway complement inhibitor for treatment of paroxysmal nocturnal hemoglobinuria

The complement system, a critical component of the human innate immune system, enhances the ability to clear microbes and damaged cells. Dysregulation of this system, particularly the alternative pathway (AP), can lead to several rare blood disorders such as paroxysmal nocturnal hemoglobinuria (PNH). This study introduces SH-01, a blood parasite-derived, novel recombinant protein which selectively inhibits the AP. We show that SH-01 effectively prevents the lysis of erythrocytes isolated from PNH patients. Unlike current treatments such as eculizumab, SH-01 targets the AP without impairing the classical or lectin pathways, reducing the risk of infections and extravascular hemolysis. SH-01 functions through a unique two-stage mechanism, preventing C3b deposition and inhibiting AP C5 convertase activity while maintaining the amplification loops functionality. Immunization studies in mice showed no significant immune response against SH-01, and the protein exhibited high stability and no acute toxicity. These findings suggest SH-01 as a promising candidate for treatment of PNH and other diseases characterized by AP hyperactivation, offering a more targeted therapeutic and thus safer approach.

immunology↗

bioRxiv2021

Insularity forcing on plant persistence strategies in edaphic island systems

AimTrait-based approaches are increasingly implemented in island biogeography, providing key insights into the eco-evolutionary dynamics of insular systems. However, what determines persistence of plant species once they have arrived and established in an island remains largely unexplored. Here, we examined links between non-acquisitive persistence strategies and insularity across three terrestrial edaphic island systems, hypothesising that insularity promotes strategies for local persistence. LocationEurope: Western Carpathians, Moravia, and Cantabrian Range. Time periodPresent. Major taxa studiedVascular plants. MethodsFor each system, we used linear models at the island scale to test whether persistence-related plant trait patterns (average trait values and diversity) depend on three insularity metrics (island size, isolation and target effect). We focused on patterns of edaphic island specialists because, in contrast to matrix-derived species, their presence is confined to the edaphic islands. ResultsWe found that insularity metrics explained large proportions in the variation of the average and diversity of persistence-related traits of edaphic island specialists. Insularity was associated with a decline in the proportion of island specialists that have clonal abilities, yet it affected trait values of specialists towards enhanced abilities to persist locally (e.g. more extensive lateral spread) while reducing trait variability. Higher degrees of insularity within the systems were translated to stronger effects on functional trait patterns. Main conclusionsInsularity affects plant species diversity, distribution and forms in terrestrial island-like systems, similarly as it is assumed for true islands. Insularity - measured using a single (island size, isolation) or combined (target effect) predictors - may operate selecting for enhanced and less diverse persistence strategies. Ultimately, this process, which we call insularity forcing, operates as a selective process to promote species ability to avoid local extinction and to persist on terrestrial islands.

ecology↗