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Computing and networking are increasingly implemented in software. We design and build a software build assurance scheme detecting if there have been injections or modifications in the various steps in the software supply chain, including the source code, compiling, and distribution. Building on the reproducible build and software bill of materials (SBOM), our work is distinguished from previous research in assuring multiple software artifacts across the software supply chain. Reproducible build, in particular, enables our scheme, as our scheme requires the software materials/artifacts to be consistent across machines with the same operating system/specifications. Furthermore, we use blockchain to deliver the proof reference, which enables our scheme to be distributed so that the assurance beneficiary and verifier are the same, i.e., the node downloading the software verifies its own materials, artifacts, and outputs. Blockchain also significantly improves the assurance efficiency. We first describe and explain our scheme using abstraction and then implement our scheme to assure Ethereum as the target software to provide concrete proof-of-concept implementation, validation, and experimental analyses. Our scheme enables more significant performance gains than relying on a centralized server thanks to the use of blockchain (e.g., two to three orders of magnitude quicker in verification) and adds small overheads (e.g., generating and verifying proof have an overhead of approximately one second, which is two orders of magnitude smaller than the software download or build processes). 

Abstract Impaired organelle-specific protein import triggers a variety of cellular stress responses, including adaptive pathways to balance protein homeostasis. Most of the previous studies focus on the cellular stress response triggered by misfolded proteins or defective protein import in the endoplasmic reticulum or mitochondria. However, little is known about the cellular stress response to impaired protein import in the peroxisome, an understudied organelle that has recently emerged as a key signaling hub for cellular and metabolic homeostasis. To uncover evolutionarily conserved cellular responses upon defective peroxisomal import, we carried out a comparative transcriptomic analysis on fruit flies with tissue-specific peroxin knockdown and human HEK293 cells expressing dominant-negative PEX5C11A. Our RNA-seq results reveal that defective peroxisomal import upregulates integrated stress response (ISR) and downregulates ribosome biogenesis in both flies and human cells. Functional analyses confirm that impaired peroxisomal import induces eIF2α phosphorylation and ATF4 expression. Loss of ATF4 exaggerates cellular damage upon peroxisomal import defects, suggesting that ATF4 activation serves as a cellular cytoprotective mechanism upon peroxisomal import stress. Intriguingly, we show that peroxisomal import stress decreases the expression of rRNA processing genes and inhibits early pre-rRNA processing, which leads to the accumulation of 47S precursor rRNA and reduction of downstream rRNA intermediates. Taken together, we identify ISR activation and ribosome biogenesis inhibition as conserved adaptive stress responses to defective peroxisomal import and uncover a novel link between peroxisomal dysfunction and rRNA processing. 

Cryptocurrency software implements the cryptocurrency operations. We design a software assurance scheme for cryptocurrency and advance the cryptocurrency handshaking protocol. More specifically, we focus on Bitcoin for implementation and integration and advance its Version-message based hand-shaking and thus call our scheme Version++, The Version++ protocol provides software assurance, which is distinguishable from the previous research because it is permissionless, distributed, and lightweight to fit its cryptocurrency application. Utilizing Merkle Tree for the verification efficiency, we implement and test Version++ on Bitcoin software and conduct experiments in an active Bitcoin node prototype connected to the Bitcoin Mainnet. This paper for the conference demonstration supplements our technical paper at CCNC 2023 for synergy but highlights the prototyping and demonstration components of our research. 

Cryptocurrency software implements the cryptocurrency operations, including the distributed consensus protocol and the peer-to-peer networking. We design a software assurance scheme for cryptocurrency and advance the cryptocurrency handshaking protocol. Since we focus on Bitcoin (the most popular cryptocurrency) for implementation and integration, we call our scheme Version++, built on and advancing the current Bitcoin handshaking protocol based on the Version message. Our Version++ protocol providing software assurance is distinguishable from the previous research because it is permissionless, distributed, and lightweight to fit its cryptocurrency application. Our scheme is permissionless since it does not require a centralized trusted authority (unlike the remote software attestation techniques from trusted computing); it is distributed since the peer checks the software assurances of its own peer connections; and it is designed for efficiency/lightweight due to the dynamic nature of the peer connections and the large-scale broadcasting in cryptocurrency networking. Utilizing Merkle Tree for the efficiency of the proof verification, we implement and test Version++ on Bitcoin software and conduct experiments in an active Bitcoin node prototype connected to the Bitcoin Mainnet. Our prototype-based performance analyses demonstrate the lightweight design of Version++. The peer-specific verification grows logarithmically with the number of software files in processing time and in storage. In addition, the Version++ verification overhead is small compared to the overall handshaking process; our measured overhead of 2.22% with minimal networking latency between the virtual machines provides an upper bound in the real-world networking with greater handshaking duration, i.e., the relative Version++ overhead in the real world with physically separate machines will be smaller. 

De novo lipogenesis is a highly regulated metabolic process, which is known to be activated through transcriptional regulation of lipogenic genes, including fatty acid synthase (FASN). Unexpectedly, we find that the expression of FASN protein remains unchanged during Drosophila larval development from the second to the third instar larval stages (L2 to L3) when lipogenesis is hyperactive. Instead, acetylation of FASN is significantly upregulated in fast-growing larvae. We further show that lysine K813 residue is highly acetylated in developing larvae, and its acetylation is required for elevated FASN activity, body fat accumulation, and normal development. Intriguingly, K813 is autoacetylated by acetyl-CoA (AcCoA) in a dosage-dependent manner independent of acetyltransferases. Mechanistically, the autoacetylation of K813 is mediated by a novel P-loop-like motif (N-xx-G-x-A). Lastly, we find that K813 is deacetylated by Sirt1, which brings FASN activity to baseline level. In summary, this work uncovers a previously unappreciated role of FASN acetylation in developmental lipogenesis and a novel mechanism for protein autoacetylation, through which Drosophila larvae control metabolic homeostasis by linking AcCoA, lysine acetylation, and de novo lipogenesis. 

Abstract The Midwest Aging Consortium (MAC) has emerged as a critical collaborative initiative aimed at advancing our understanding of aging and developing strategies to combat the rising prevalence of age-related diseases. Founded in 2019, MAC brings together researchers from various disciplines and institutions across the Midwestern United States to foster interdisciplinary geroscience research. This report summarizes the highlights of the Fourth Annual Symposium of MAC, which was held at Iowa State University in May 2023. The symposium featured presentations on a wide array of topics, including studies on slow-aging animals, cellular senescence and senotherapeutics, the role of the immune system in aging, metabolic changes in aging, neuronal health in aging, and biomarkers for measuring the aging process. Speakers shared findings from studies involving a variety of animals, ranging from commonly used species such as mice, rats, worms, yeast, and fruit flies, to less-common ones like naked mole-rats, painted turtles, and rotifers. MAC continues to emphasize the importance of supporting emerging researchers and fostering a collaborative environment, positioning itself as a leader in aging research. This symposium not only showcased the current state of aging biology research but also highlighted the consortium’s role in training the next generation of scientists dedicated to improving the healthspan and well-being of the aging population. 

Blockchain relies on the underlying peer-to-peer (P2P) networking to broadcast and get up-to-date on the blocks and transactions. Because of the blockchain operations’ reliance on the information provided by P2P networking, it is imperative to have high P2P connectivity for the quality of the blockchain system operations and performances. High P2P networking connectivity ensures that a peer node is connected to multiple other peers providing a diverse set of observers of the current state of the blockchain and transactions. However, in a permissionless Bitcoin cryptocurrency network, using the peer identifiers – including the current approach of counting the number of distinct IP addresses and port numbers – can be ineffective in measuring the number of peer connections and estimating the networking connectivity. Such current approach is further challenged by the networking threats manipulating identities. We build a robust estimation engine for the P2P networking connectivity by sensing and processing the P2P networking traffic. We take a systematic approach to study our engine and analyze the followings: the different components of the connectivity estimation engine and how they affect the accuracy performances, the role and the effectiveness of an outlier detection to enhance the connectivity estimation, and the engine’s interplay with the Bitcoin protocol. We implement a working Bitcoin prototype connected to the Bitcoin mainnet to validate and improve our engine’s performances and evaluate the estimation accuracy and cost efficiency of our connectivity estimation engine. Our results show that our scheme effectively counters the identity-manipulations threats, achieves 96.4% estimation accuracy with a tolerance of one peer connection, and is lightweight in the overheads in the mining rate, thus making it appropriate for the miner deployment.