A basic helix-loop-helix transcription factor, PhFBH4, regulates flower senescence by modulating ethylene biosynthesis pathway in petunia.

The basic helix-loop-helix (bHLH) transcription factors (TFs) play important roles in regulating multiple biological processes in plants. However, there are few reports about the function of bHLHs in flower senescence. In this study, a bHLH TF, PhFBH4, was found to be dramatically upregulated during flower senescence. Transcription of PhFBH4 is induced by plant hormones and abiotic stress treatments. Silencing of PhFBH4 using virus-induced gene silencing or an antisense approach extended flower longevity, while transgenic petunia flowers with an overexpression construct showed a reduction in flower lifespan. Abundance of transcripts of senescence-related genes (SAG12, SAG29) was significantly changed in petunia PhFBH4 transgenic flowers. Furthermore, silencing or overexpression of PhFBH4 reduced or increased, respectively, transcript abundances of important ethylene biosynthesis-related genes, ACS1 and ACO1, thereby influencing ethylene production. An electrophoretic mobility shift assay showed that the PhFBH4 protein physically interacted with the G-box cis-element in the promoter of ACS1, suggesting that ACS1 was a direct target of the PhFBH4 protein. In addition, ectopic expression of this gene altered plant development including plant height, internode length, and size of leaves and flowers, accompanied by alteration of transcript abundance of the gibberellin biosynthesis-related gene GA2OX3. Our results indicate that PhFBH4 plays an important role in regulating plant growth and development through modulating the ethylene biosynthesis pathway

A Petunia homeodomain-leucine zipper protein, PhHD-Zip, plays an important role in flower senescence.

Flower senescence is initiated by developmental and environmental signals, and regulated by gene transcription. A homeodomain-leucine zipper transcription factor, PhHD-Zip, is up-regulated during petunia flower senescence. Virus-induced gene silencing of PhHD-Zip extended flower life by 20% both in unpollinated and pollinated flowers. Silencing PhHD-Zip also dramatically reduced ethylene production and the abundance of transcripts of genes involved in ethylene (ACS, ACO), and ABA (NCED) biosynthesis. Abundance of transcripts of senescence-related genes (SAG12, SAG29) was also dramatically reduced in the silenced flowers. Over-expression of PhHD-Zip accelerated petunia flower senescence. Furthermore, PhHD-Zip transcript abundance in petunia flowers was increased by application of hormones (ethylene, ABA) and abiotic stresses (dehydration, NaCl and cold). Our results suggest that PhHD-Zip plays an important role in regulating petunia flower senescence

Lack of VMP1 impairs hepatic lipoprotein secretion and promotes non-alcoholic steatohepatitis

BACKGROUND & AIMS: Vacuole membrane protein 1 (VMP1) is an endoplasmic reticulum (ER) transmembrane protein that regulates the formation of autophagosomes and lipid droplets. Recent evidence suggests that VMP1 plays a critical role in lipoprotein secretion in zebra fish and cultured cells. However, the pathophysiological roles and mechanisms by which VMP1 regulates lipoprotein secretion and lipid accumulation in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are unknown. METHODS: Liver-specific and hepatocyte-specific Vmp1 knockout mice as well as Vmp1 knock-in mice were generated by crossing Vmp1 RESULTS: Hepatocyte-specific deletion of Vmp1 severely impaired VLDL secretion resulting in massive hepatic steatosis, hepatocyte death, inflammation and fibrosis, which are hallmarks of NASH. Mechanistically, loss of Vmp1 led to decreased hepatic levels of phosphatidylcholine and phosphatidylethanolamine as well as to changes in phospholipid composition. Deletion of Vmp1 in mouse liver also led to the accumulation of neutral lipids in the ER bilayer and impaired mitochondrial beta-oxidation. Overexpression of VMP1 ameliorated steatosis in diet-induced NASH by improving VLDL secretion. Importantly, we also showed that decreased liver VMP1 is associated with NAFLD/NASH in humans. CONCLUSIONS: Our results provide novel insights on the role of VMP1 in regulating hepatic phospholipid synthesis and lipoprotein secretion in the pathogenesis of NAFLD/NASH. LAY SUMMARY: Non-alcoholic fatty liver disease and its more severe form, non-alcoholic steatohepatitis, are associated with a build-up of fat in the liver (steatosis). However, the exact mechanisms that underly steatosis in patients are not completely understood. Herein, the authors identified that the lack of a protein called VMP1 impairs the secretion and metabolism of fats in the liver and could therefore contribute to the development and progression of non-alcoholic fatty liver disease

UniFed: A Unified Framework for Federated Learning on Non-IID Image Features

How to tackle non-iid data is a crucial topic in federated learning. This challenging problem not only affects training process, but also harms performance of clients not participating in training. Existing literature mainly focuses on either side, yet still lacks a unified solution to handle these two types (internal and external) of clients in a joint way. In this work, we propose a unified framework to tackle the non-iid issues for internal and external clients together. Firstly, we propose to use client-specific batch normalization in either internal or external clients to alleviate feature distribution shifts incurred by non-iid data. Then we present theoretical analysis to demonstrate the benefits of client-specific batch normalization. Specifically, we show that our approach promotes convergence speed for federated training and yields lower generalization error bound for external clients. Furthermore, we use causal reasoning to form a causal view to explain the advantages of our framework. At last, we conduct extensive experiments on natural and medical images to evaluate our method, where our method achieves state-of-the-art performance, faster convergence, and shows good compatibility. We also performed comprehensive analytical studies on a real-world medical dataset to demonstrate the effectiveness

FedSoup: Improving Generalization and Personalization in Federated Learning via Selective Model Interpolation

Cross-silo federated learning (FL) enables the development of machine learning models on datasets distributed across data centers such as hospitals and clinical research laboratories. However, recent research has found that current FL algorithms face a trade-off between local and global performance when confronted with distribution shifts. Specifically, personalized FL methods have a tendency to overfit to local data, leading to a sharp valley in the local model and inhibiting its ability to generalize to out-of-distribution data. In this paper, we propose a novel federated model soup method (i.e., selective interpolation of model parameters) to optimize the trade-off between local and global performance. Specifically, during the federated training phase, each client maintains its own global model pool by monitoring the performance of the interpolated model between the local and global models. This allows us to alleviate overfitting and seek flat minima, which can significantly improve the model's generalization performance. We evaluate our method on retinal and pathological image classification tasks, and our proposed method achieves significant improvements for out-of-distribution generalization. Our code is available at https://github.com/ubc-tea/FedSoup.Comment: Accepted by MICCAI202

Client-Level Differential Privacy via Adaptive Intermediary in Federated Medical Imaging

Despite recent progress in enhancing the privacy of federated learning (FL) via differential privacy (DP), the trade-off of DP between privacy protection and performance is still underexplored for real-world medical scenario. In this paper, we propose to optimize the trade-off under the context of client-level DP, which focuses on privacy during communications. However, FL for medical imaging involves typically much fewer participants (hospitals) than other domains (e.g., mobile devices), thus ensuring clients be differentially private is much more challenging. To tackle this problem, we propose an adaptive intermediary strategy to improve performance without harming privacy. Specifically, we theoretically find splitting clients into sub-clients, which serve as intermediaries between hospitals and the server, can mitigate the noises introduced by DP without harming privacy. Our proposed approach is empirically evaluated on both classification and segmentation tasks using two public datasets, and its effectiveness is demonstrated with significant performance improvements and comprehensive analytical studies. Code is available at: https://github.com/med-air/Client-DP-FL.Comment: Accepted by 26th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI'23

Mutations in Amino Acid Residues of Limosilactobacillus reuteri 121 GtfB 4,6-α-Glucanotransferase that Affect Reaction and Product Specificity

Limosilactobacillus reuteri 121 4,6-α-glucanotransferase (Lr121 4,6-α-GTase), belonging to the glycosyl hydrolase (GH) 70 GtfB subfamily, converts starch and maltodextrins into linear isomalto/malto polysaccharides (IMMPs) with consecutive (α1 → 6) linkages. The recent elucidation of its crystal structure allowed identification and analysis of further structural features that determine its reaction and product specificity. Herein, sequence alignments between GtfB enzymes with different product linkage specificities (4,6-α-GTase and 4,3-α-GTase) identified amino acid residues in GH70 homology motifs, which may be critical for reaction and product specificity. Based on these alignments, four Lr121 GtfB-ΔN mutants (I1020M, S1057P, H1056G, and Q1126I) were constructed. Compared to wild-type Lr121 GtfB-ΔN, mutants S1057P and Q1126I had considerably improved catalytic efficiencies. Mutants H1056G and Q1126I showed a 9% decrease and an 11% increase, respectively, in the ratio of (α1 → 6) over (α1 → 4) linkages in maltodextrin-derived products. A change in linkage type (e.g., (α1 → 6) linkages to (α1 → 3) linkages) was not observed. The possible functional roles of these Lr121 GtfB-ΔN residues located around the acceptor substrate-binding subsites are discussed. The results provide new insights into structural determinants of the reaction and product specificity of Lr121 GtfB 4,6-α-GTase