3 research outputs found
SubTuning: Efficient Finetuning for Multi-Task Learning
Finetuning a pretrained model has become a standard approach for training
neural networks on novel tasks, resulting in fast convergence and improved
performance. In this work, we study an alternative finetuning method, where
instead of finetuning all the weights of the network, we only train a carefully
chosen subset of layers, keeping the rest of the weights frozen at their
initial (pretrained) values. We demonstrate that \emph{subset finetuning} (or
SubTuning) often achieves accuracy comparable to full finetuning of the model,
and even surpasses the performance of full finetuning when training data is
scarce. Therefore, SubTuning allows deploying new tasks at minimal
computational cost, while enjoying the benefits of finetuning the entire model.
This yields a simple and effective method for multi-task learning, where
different tasks do not interfere with one another, and yet share most of the
resources at inference time. We demonstrate the efficiency of SubTuning across
multiple tasks, using different network architectures and pretraining methods
AMPK regulates ER morphology and function in stressed pancreatic β-cells via phosphorylation of DRP1
Experimental lipotoxicity constitutes a model for β-cell demise induced by metabolic stress in obesity and type 2 diabetes. Fatty acid excess induces endoplasmic reticulum (ER) stress, which is accompanied by ER morphological changes whose mechanisms and relevance are unknown. We found that the GTPase dynamin-related protein 1 (DRP1), a key regulator of mitochondrial fission, is an ER resident regulating ER morphology in stressed β-cells. Inhibition of DRP1 activity using a GTP hydrolysis-defective mutant (Ad-K38A) attenuated fatty acid-induced ER expansion and mitochondrial fission. Strikingly, stimulating the key energy-sensor AMP-activated protein kinase (AMPK) increased the phosphorylation at the anti-fission site Serine 637 and largely prevented the alterations in ER and mitochondrial morphology. Expression of a DRP1 mutant resistant to phosphorylation at this position partially prevented the recovery of ER and mitochondrial morphology by AMPK. Fatty acid-induced ER enlargement was associated with proinsulin retention in the ER, together with increased proinsulin/insulin ratio. Stimulation of AMPK prevented these alterations, as well as mitochondrial fragmentation and apoptosis. In summary, DRP1 regulation by AMPK delineates a novel pathway controlling ER and mitochondrial morphology, thereby modulating the response of β-cells to metabolic stress. DRP1 may thus function as a node integrating signals from stress regulators, such as AMPK, to coordinate organelle shape and function
AMPK Regulates ER Morphology and Function in Stressed Pancreatic β-Cells via Phosphorylation of DRP1
Experimental lipotoxicity constitutes a model for β-cell demise induced by metabolic stress in obesity and type 2 diabetes. Fatty acid excess induces endoplasmic reticulum (ER) stress, which is accompanied by ER morphological changes whose mechanisms and relevance are unknown. We found that the GTPase dynamin-related protein 1 (DRP1), a key regulator of mitochondrial fission, is an ER resident regulating ER morphology in stressed β-cells. Inhibition of DRP1 activity using a GTP hydrolysis-defective mutant (Ad-K38A) attenuated fatty acid-induced ER expansion and mitochondrial fission. Strikingly, stimulating the key energy-sensor AMP-activated protein kinase (AMPK) increased the phosphorylation at the anti-fission site Serine 637 and largely prevented the alterations in ER and mitochondrial morphology. Expression of a DRP1 mutant resistant to phosphorylation at this position partially prevented the recovery of ER and mitochondrial morphology by AMPK. Fatty acid-induced ER enlargement was associated with proinsulin retention in the ER, together with increased proinsulin/insulin ratio. Stimulation of AMPK prevented these alterations, as well as mitochondrial fragmentation and apoptosis. In summary, DRP1 regulation by AMPK delineates a novel pathway controlling ER and mitochondrial morphology, thereby modulating the response of β-cells to metabolic stress. DRP1 may thus function as a node integrating signals from stress regulators, such as AMPK, to coordinate organelle shape and function