A substrate-specific mTORC1 pathway underlies Birt–Hogg–Dubé syndrome

Standing genetic variation in a tissue-specific enhancer underlies selfing-syndrome evolution in Capsella.

Mating system shifts recurrently drive specific changes in organ dimensions. The shift in mating system from out-breeding to selfing is one of the most frequent evolutionary transitions in flowering plants and is often associated with an organ-specific reduction in flower size. However, the evolutionary paths along which polygenic traits, such as size, evolve are poorly understood. In particula...

White matter pathway asymmetry underlies functional lateralization.

Structural and functional asymmetry of the human brain has been well documented using techniques such as magnetic resonance imaging (MRI). However, asymmetry of underlying white matter connections is less well understood. We applied an MRI technique known as diffusion tensor tractography to reveal the morphology of the white matter in vivo by mapping directions of maximum water diffusion in bra...

Epistasis Analysis of a Substrate - Dependent Pathway

Substrate-Specific Translocational Attenuation during ER Stress Defines a Pre-Emptive Quality Control Pathway

Eukaryotic proteins entering the secretory pathway are translocated into the ER by signal sequences that vary widely in primary structure. We now provide a functional rationale for this long-observed sequence diversity by demonstrating that differences among signals facilitate substrate-selective modulation of protein translocation. We find that during acute ER stress, translocation of secretor...

mTORC1-Dependent Metabolic Reprogramming Underlies Escape from Glycolysis Addiction in Cancer Cells.

Although glycolysis is substantially elevated in many tumors, therapeutic targeting of glycolysis in cancer patients has not yet been successful, potentially reflecting the metabolic plasticity of tumor cells. In various cancer cells exposed to a continuous glycolytic block, we identified a recurrent reprogramming mechanism involving sustained mTORC1 signaling that underlies escape from glycoly...