Search bioRxiv⌕ Search

Biology subjects

Binelli, G.

Publications and source records attributed to Binelli, G..

2 recordsLinked to original sources

The end of the American dream: a hard to Swallow reality - How the Barn Swallow (Hirundo rustica) returned from America, a complete mtDNA phylogeny

The barn swallow (Hirundo rustica, H.r.) is one of the most iconic and fascinating migratory birds since ancient times, their philopatry and pair bonding have been the symbol of travellers and lovers throughout history. The barn swallow subspecies complex has been the main focus of many latest papers, focusing mainly on the Eurasian and Levant subspecies (H.r. rustica and H.r. transitiva). The remaining subspecies have either not been studied or few complete mitogenome sequences have been obtained. We present a comprehensive phylogeographic analysis of 580 complete mitochondrial genomes of barn swallows representing all recognized subspecies. We identified 553 unique haplotypes, 166 of which are novel, with high haplotype diversity and notable nucleotide diversity among subspecies. Phylogenetic analysis by maximum parsimony supports a single maternal ancestor and reveals five main haplogroups, confirming and refining prior classifications. A novel, distinct haplogroup (E) was identified for H.r. tytleri, previously classified as a sub-branch of H.r. erythrogaster. The inclusion of 66 hybrid individuals confirmed extensive maternal introgression and revealed multiple cases of mitogenome-subspecies mismatches, notably in savignii, transitiva, and tytleri populations. We further integrated 13 mitogenomes from 12 other Hirundo species, three of which are newly sequenced, to contextualize H. rustica evolution within the genus. Our findings support a southern African origin with subsequent diversification and a northward expansion. This study significantly enhances resolution of barn swallow mitogenomic diversity, revises phylogenetic relationships, identifies new haplogroups, hints at inter-subspecies gene flow and refines coalescent-based divergence times, offering key insights into the evolutionary history and hybridisation patterns of this iconic migratory species.

evolutionary biology↗

Oxidative stress potentiates the therapeutic action of a mitochondrial complex I inhibitor in MYC-driven B-cell lymphoma

MYC is a key oncogenic driver and an adverse prognostic factor in multiple types of cancer, including diffuse large B-cell lymphoma (DLBCL). Yet, MYC activation also endows cancer cells with a series of metabolic dependencies, which can provide strategic points for targeted pharmacological intervention. We recently reported that targeting the mitochondrial electron transport chain (ETC) complex I with the small molecule inhibitor IACS-010759 selectively killed MYC-overexpressing lymphoid cells. Here, we unravel the mechanistic basis for this synthetic-lethal interaction and exploit it to improve the anti-tumoral effects of ETC inhibition. In a mouse B-cell line, MYC hyperactivation and IACS-010759 treatment added up to induce oxidative stress, with consequent depletion of reduced glutathione and lethal disruption of redox homeostasis. This effect could be enhanced by targeted pharmacological intervention, with either inhibitors of NADPH production through the pentose phosphate pathway, or with ascorbate (vitamin C), known to contribute pro-oxidant effects when administered at high doses. In these conditions, ascorbate synergized with IACS-010759 to kill MYC-overexpressing cells in vitro and reinforced its therapeutic action against human B-cell lymphoma xenografts. Hence, ETC inhibition and high-dose ascorbate might improve the outcome of patients affected by high-grade lymphomas and other MYC-driven cancers. Key point #1MYC and the ETC complex I inhibitor IACS-010759 elicit different reactive oxygen species (ROS) that cooperate to disrupt redox homeostasis. Key point #2Further boosting of oxidative stress with high doses of ascorbate increases the killing of MYC-driven lymphoma xenografts by IACS-010759.

cancer biology↗