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Chung, Y.-H.

Publications and source records attributed to Chung, Y.-H..

2 recordsLinked to original sources

Ground nesting of soft eggs by extinct birds and a new parity mode switch hypothesis for the evolution of animal reproduction

Nearshore ground nesting of soft eggs by extinct birds is demonstrated here, providing a new explanation for the abundance of bird fossils in early Cretaceous lacustrine environments, where humidity conditions required for soft egg incubation would have been present. This reinforces recent findings of Archaeopteryx soft eggs near Jurassic marine environments, the possibility that wings and elongated feathers developed primarily in association with nest protection on the ground and only secondarily with flight, and the origin of flight from the ground up. Notably, soft eggs preceded rigid eggs in evolution, but both crocodiles, whose ancestors seem to have antedated bird precursors, and extant birds reproduce exclusively via hard-shelled eggs. Therefore, an explanation is in order for how reproduction via soft eggs could have occurred in the bird lineage in-between two evolutionary moments of reproduction via rigid eggs. In alternative to the commonly accepted convergent evolution of viviparity and rigid eggshells, a parity mode switch hypothesis is presented here. It postulates the existence, since the rise of animals, of an inherited ancestral parity mode switch between viviparity and oviparity. This switch would have evolved to embrace hard-shelled oviparity after rigid eggshells appeared in evolution. Commitment to a particular parity mode or eggshell type may have conditioned survival of entire animal groups, especially during major extinction events, explaining, among others, the extinction of all birds that reproduced via soft eggshells.

evolutionary biology↗

Targeting Reductive Metabolic Shifts by T315I Mutation in BCR-ABL Myeloid Leukemia for Therapy

T315I mutation of Bcr-Abl in chronic myeloid leukemia (CML) leads to therapeutic resistance. It is known that Bcr-Abl transformation causes ROS-induced DNA damages and replication stress, which can be exploited for anti-nucleotide therapy. We developed a small compound, JMF4073, which inhibited pyrimidylate kinases and selectively eliminated Bcr-Abl-transformed, but not untransformed myeloid cells, due to dTTP exhaustion and ROS-induced replication stress. However, T315I-Bcr-Abl-transformed cells were less vulnerable to JMF4073 because of higher dTTP pool and low replication stress. Unlike WT-Bcr-Abl-transformed cells, T315I-Bcr-Abl cells lacked Sirt1- regulated OXPHOS with increased glutamine flux to reductive carboxylation in TCA cycle and glutathione synthesis. Blocking mitochondrial pyruvate carrier (MPC) by UK-5099 reduced NADH and glutathione levels with replication stress induction, thereby converting T315I-Bcr-Abl cells sensitive to JMF4073 with dTTP and dCTP depletion. The combination of JMF4073 with UK-5099 showed in vivo eradication of T315I-Bcr-Abl-CML. These data reveal that T315I mutation causes reductive metabolic shifts in Bcr-Abl-CML, and demonstrate the therapeutic option by co-targeting MPC and pyrimidylate kinases.

cancer biology↗