Acetylation-defective mutant of Pparγ is associated with decreased lipid synthesis in breast cancer cells.

In our prior publications we characterized a conserved acetylation motif (K(R)xxKK) of evolutionarily related nuclear receptors. Recent reports showed that peroxisome proliferator activated receptor gamma (PPARγ) deacetylation by SIRT1 is involved in delaying cellular senescence and maintaining the brown remodeling of white adipose tissue. However, it still remains unknown whether lysyl residues 154 and 155 (K154/155) of the conserved acetylation motif (RIHKK) in Pparγ1 are acetylated. Herein, we demonstrate that Pparγ1 is acetylated and regulated by both endogenous TSA-sensitive and NAD-dependent deacetylases. Acetylation of lysine 154 was identified by mass spectrometry (MS) while deacetylation of lysine 155 by SIRT1 was confirmed by in vitro deacetylation assay. An in vivo labeling assay revealed K154/K155 as bona fide acetylation sites. The conserved acetylation sites of Pparγ1 and the catalytic domain of SIRT1 are both required for the interaction between Pparγ1 and SIRT1. Sirt1 and Pparγ1 converge to govern lipid metabolism in vivo. Acetylation-defective mutants of Pparγ1 were associated with reduced lipid synthesis in ErbB2 overexpressing breast cancer cells. Together, these results suggest that the conserved lysyl residues K154/K155 of Pparγ1 are acetylated and play an important role in lipid synthesis in ErbB2-positive breast cancer cells

LEASE: Leveraging Energy-Awareness in Serverless Edge for Latency-Sensitive IoT Services

Resource Scheduling Catering to Real-Time IoT Services in a Serverless-Enabled Edge Network is Particularly Challenging Owing to the Workload Variability, Strict Constraints on Tolerable Latency, and Unpredictability in the Energy Sources Powering the Edge Devices. This Paper Proposes a Framework LEASE that Dynamically Schedules Resources in Serverless Functions Catering to Different Microservices and Adhering to their Deadline Constraint. to Assist the Scheduler in Making Effective Scheduling Decisions, We Introduce a Priority-Based Approach that Offloads Functions from over-Provisioned Edge Nodes to Under-Provisioned Peer Nodes, Considering the Expended Energy in the Process Without Compromising the Completion Time of Microservices. for Real-World Implementations, We Consider a Testbed Comprising a Raspberry Pi Cluster Serving as Edge Nodes, Equipped with Container Orchestrator Tools Such as Kubernetes and Powered by OpenFaaS, an Open-Source Serverless Platform. Experimental Results Demonstrate that Compared to the Benchmarking Algorithm, LEASE Achieves a 23.34% Reduction in the overall Completion Time, with 97.64% of Microservices Meeting their Deadline. LEASE Also Attains a 30.10% Reduction in Failure Rates

Geo-distributed Multi-tier Workload Migration Over Multi-timescale Electricity Markets

Virtual machine (VM) migration enables cloud service providers (CSPs) to balance workload, perform zero-downtime maintenance, and reduce applications\u27 power consumption and response time. Migrating a VM consumes energy at the source, destination, and backbone networks, i.e., intermediate routers and switches, especially in a Geo-distributed setting. In this context, we propose a VM migration model called Low Energy Application Workload Migration (LEAWM) aimed at reducing the per-bit migration cost in migrating VMs over Geo-distributed clouds. With a Geo-distributed cloud connected through multiple Internet Service Providers (ISPs), we develop an approach to find out the migration path across ISPs leading to the most feasible destination. For this, we use the variation in the electricity price at the ISPs to decide the migration paths. However, reduced power consumption at the expense of higher migration time is intolerable for real-time applications. As finding an optimal relocation is $\mathcal {NP}$-Hard, we propose an Ant Colony Optimization (ACO) based bi-objective optimization technique to strike a balance between migration delay and migration power. A thorough simulation analysis of the proposed approach shows that the proposed model can reduce the migration time by $25\%$–$30\%$ and electricity cost by approximately $25\%$ compared to the baseline

Cell Cycle- and Cancer-Associated Gene Networks Activated by Dsg2: Evidence of Cystatin A Deregulation and a Potential Role in Cell-Cell Adhesion

This work was supported by grants from the National Institutes of Health (Mahoney, R01AR056067; Riobo, RO1 GM088256). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Adult Zymosan Re-Exposure Exacerbates the Molecular Alterations in the Brainstem Rostral Ventromedial Medulla of Rats With Early Life Zymosan-Induced Cystitis

Recent evidence suggests that the descending modulatory pathways from the brainstem rostral ventromedial medulla (RVM) are important for bladder inflammatory pain. This study aimed to identify the long-term molecular changes in RVM neurons due to early life cystitis during neuronal development and the effect of reexposure later in adulthood. RVM tissues from two treatment protocols were used: (1) neonatal zymosan exposures with acute adult rechallenge (RC) and (2) only neonatal zymosan exposures (NRC). RNAseq analysis showed upregulation of several genes associated with synaptic plasticity (Grin1, Grip2, Notch1, Arc, and Scn2b) in the cystitis groups compared to controls in both protocols. The RC protocol exhibited a stronger treatment effect with significantly higher fold differences between the groups compared to the NRC protocol (p \u3c 0.001, fold differences RC vs NRC). In microarrays, miR-34a-5p showed cystitis-induced downregulation in both protocols. Bioinformatics analysis identified multiple 3′UTRs complementary binding sites for miR-34a-5p on Grin2b, Notch1, Grip2, Scn2b, and Arc genes. The enhanced response in the RC protocol indicates a possible priming effect of early life cystitis on rechallenge in adulthood. These long-term molecular alterations may play a critical role in the development of chronic bladder pain conditions as seen in patients with Interstitial Cystitis/Bladder pain syndrome

The endogenous cell-fate factor dachshund restrains prostate epithelial cell migration via repression of cytokine secretion via a CXCL signaling module

© 2015 American Association for Cancer Research. Prostate cancer is the second leading form of cancer-related death in men. In a subset of prostate cancer patients, increased chemokine signaling IL8 and IL6 correlates with castrate-resistant prostate cancer (CRPC). IL8 and IL6 are produced by prostate epithelial cells and promote prostate cancer cell invasion; however, the mechanisms restraining prostate epithelial cell cytokine secretion are poorly understood. Herein, the cell-fate determinant factor DACH1 inhibited CRPC tumor growth in mice. Using Dach1fl/fl/Probasin-Cre bitransgenic mice, we show IL8 and IL6 secretion was altered by approximately 1,000-fold by endogenous Dach1. Endogenous Dach1 is shown to serve as a key endogenous restraint to prostate epithelial cell growth and restrains migration via CXCL signaling. DACH1 inhibited expression, transcription, and secretion of the CXCL genes (IL8 and IL6) by binding to their promoter regulatory regions in chromatin. DACH1 is thus a newly defined determinant of benign and malignant prostate epithelium cellular growth, migration, and cytokine abundance in vivo

Compartment-Restricted Biotinylation Reveals Novel Features of Prion Protein Metabolism in Vivo

A selective tagging method for detecting minor alternatively-localized populations of a protein is used to study a disease-associated transmembrane form of prion protein. The analysis reveals key features of transmembrane prion protein metabolism and one way this is altered by human disease-causing mutants