The venom gland transcriptome of the Desert Massasauga Rattlesnake (Sistrurus catenatus edwardsii): towards an understanding of venom composition among advanced snakes (Superfamily Colubroidea)

<p>Abstract</p> <p>Background</p> <p>Snake venoms are complex mixtures of pharmacologically active proteins and peptides which belong to a small number of superfamilies. Global cataloguing of the venom transcriptome facilitates the identification of new families of toxins as well as helps in understanding the evolution of venom proteomes.</p> <p>Results</p> <p>We have constructed a cDNA library of the venom gland of a threatened rattlesnake (a pitviper), <it>Sistrurus catenatus edwardsii </it>(Desert Massasauga), and sequenced 576 ESTs. Our results demonstrate a high abundance of serine proteinase and metalloproteinase transcripts, indicating that the disruption of hemostasis is a principle mechanism of action of the venom. In addition to the transcripts encoding common venom proteins, we detected two varieties of low abundance unique transcripts in the library; these encode for three-finger toxins and a novel toxin possibly generated from the fusion of two genes. We also observed polyadenylated ribosomal RNAs in the venom gland library, an interesting preliminary obsevation of this unusual phenomenon in a reptilian system.</p> <p>Conclusion</p> <p>The three-finger toxins are characteristic of most elapid venoms but are rare in viperid venoms. We detected several ESTs encoding this group of toxins in this study. We also observed the presence of a transcript encoding a fused protein of two well-characterized toxins (Kunitz/BPTI and Waprins), and this is the first report of this kind of fusion in a snake toxin transcriptome. We propose that these new venom proteins may have ancillary functions for envenomation. The presence of a fused toxin indicates that in addition to gene duplication and accelerated evolution, exon shuffling or transcriptional splicing may also contribute to generating the diversity of toxins and toxin isoforms observed among snake venoms. The detection of low abundance toxins, as observed in this and other studies, indicates a greater compositional similarity of venoms (though potency will differ) among advanced snakes than has been previously recognized.</p

Accelerated exchange of exon segments in Viperid three-finger toxin genes (Sistrurus catenatus edwardsii; Desert Massasauga)

<p>Abstract</p> <p>Background</p> <p>Snake venoms consist primarily of proteins and peptides showing a myriad of potent biological activities which have been shaped by both adaptive and neutral selective forces. Venom proteins are encoded by multigene families that have evolved through a process of gene duplication followed by accelerated evolution in the protein coding region.</p> <p>Results</p> <p>Here we report five gene structures of three-finger toxins from a viperid snake, <it>Sistrurus catenatus edwardsii</it>. These toxin genes are structured similarly to elapid and hydrophiid three-finger toxin genes, with two introns and three exons. Both introns and exons show distinct patterns of segmentation, and the insertion/deletion of segments may define their evolutionary history. The segments in introns, when present, are highly similar to their corresponding segments in other members of the gene family. In contrast, some segments in the exons show high similarity, while others are often distinctly different among corresponding regions of the isoforms.</p> <p>Conclusion</p> <p>Ordered, conserved exon structure strongly suggests that segments in corresponding regions in exons have been exchanged with distinctly different ones during the evolution of these genes. Such a "switching" of segments in exons may result in drastically altering the molecular surface topology and charge, and hence the molecular targets of these three-finger toxins. Thus the phenomenon of accelerated segment switch in exons to alter targeting (ASSET) may play an important role in the evolution of three-finger toxins, resulting in a family of toxins with a highly conserved structural fold but widely varying biological activities.</p

Dissecting Bitcoin and Ethereum Transactions: On the Lack of Transaction Contention and Prioritization Transparency in Blockchains

In permissionless blockchains, transaction issuers include a fee to incentivize miners to include their transaction. To accurately estimate this prioritization fee for a transaction, transaction issuers (or blockchain participants, more generally) rely on two fundamental notions of transparency, namely contention and prioritization transparency. Contention transparency implies that participants are aware of every pending transaction that will contend with a given transaction for inclusion. Prioritization transparency states that the participants are aware of the transaction or prioritization fees paid by every such contending transaction. Neither of these notions of transparency holds well today. Private relay networks, for instance, allow users to send transactions privately to miners. Besides, users can offer fees to miners via either direct transfers to miners' wallets or off-chain payments -- neither of which are public. In this work, we characterize the lack of contention and prioritization transparency in Bitcoin and Ethereum resulting from such practices. We show that private relay networks are widely used and private transactions are quite prevalent. We show that the lack of transparency facilitates miners to collude and overcharge users who may use these private relay networks despite them offering little to no guarantees on transaction prioritization. The lack of these transparencies in blockchains has crucial implications for transaction issuers as well as the stability of blockchains. Finally, we make our data sets and scripts publicly available.Comment: This is a pre-print of our paper accepted to appear to the Financial Cryptography and Data Security 2023 (FC '23

Understanding Blockchain Governance: Analyzing Decentralized Voting to Amend DeFi Smart Contracts

Smart contracts are contractual agreements between participants of a blockchain, who cannot implicitly trust one another. They are software programs that run on top of a blockchain, and we may need to change them from time to time (e.g., to fix bugs or address new use cases). Governance protocols define the means for amending or changing these smart contracts without any centralized authority. They distribute instead the decision-making power to every user of the smart contract: Users vote on accepting or rejecting every change. The focus of this work is to evaluate whether, how, and to what extent these protocols ensure decentralized governance, the fundamental tenet of blockchains, in practice. This evaluation is crucial as smart contracts continue to transform our key, traditional, centralized institutions, particularly banking and finance. In this work, we review and characterize decentralized governance in practice, using Compound -- one of the widely used governance protocols -- as a case study. We reveal a high concentration of voting power in Compound: 10 voters hold together 57.86% of the voting power. Although proposals to change or amend the protocol (or, essentially, the application they support) receive, on average, a substantial number of votes (i.e., 89.39%) in favor, they require fewer than three voters to obtain 50% or more votes. We show that voting on Compound governance proposals can be unfairly expensive for small token holders, and also discover voting coalitions that can further marginalize these users. We plan on publishing our scripts and data set on GitHub to support reproducible research.Comment: We have submitted this work for publication and are currently awaiting a decisio

The Venom Gland Transcriptome of the Desert Massasauga Rattlesnake (Sistrurus Catenatus Edwardsii): Towards an Understanding of Venom Composition Among Advanced Snakes (Superfamily Colubroidea)

BACKGROUND: Snake venoms are complex mixtures of pharmacologically active proteins and peptides which belong to a small number of superfamilies. Global cataloguing of the venom transcriptome facilitates the identification of new families of toxins as well as helps in understanding the evolution of venom proteomes. RESULTS: We have constructed a cDNA library of the venom gland of a threatened rattlesnake (a pitviper), Sistrurus catenatus edwardsii (Desert Massasauga), and sequenced 576 ESTs. Our results demonstrate a high abundance of serine proteinase and metalloproteinase transcripts, indicating that the disruption of hemostasis is a principle mechanism of action of the venom. In addition to the transcripts encoding common venom proteins, we detected two varieties of low abundance unique transcripts in the library; these encode for three-finger toxins and a novel toxin possibly generated from the fusion of two genes. We also observed polyadenylated ribosomal RNAs in the venom gland library, an interesting preliminary obsevation of this unusual phenomenon in a reptilian system. CONCLUSION: The three-finger toxins are characteristic of most elapid venoms but are rare in viperid venoms. We detected several ESTs encoding this group of toxins in this study. We also observed the presence of a transcript encoding a fused protein of two well-characterized toxins (Kunitz/BPTI and Waprins), and this is the first report of this kind of fusion in a snake toxin transcriptome. We propose that these new venom proteins may have ancillary functions for envenomation. The presence of a fused toxin indicates that in addition to gene duplication and accelerated evolution, exon shuffling or transcriptional splicing may also contribute to generating the diversity of toxins and toxin isoforms observed among snake venoms. The detection of low abundance toxins, as observed in this and other studies, indicates a greater compositional similarity of venoms (though potency will differ) among advanced snakes than has been previously recognized

Large Area X-ray Proportional Counter (LAXPC) in Orbit Performance : Calibration, background, analysis software

The Large Area X-ray Proportional Counter (LAXPC) instrument on-board AstroSat has three nominally identical detectors for timing and spectral studies in the energy range of 3--80 keV. The performance of these detectors during the five years after the launch of AstroSat is described. Currently, only one of the detector is working nominally. The variation in pressure, energy resolution, gain and background with time are discussed. The capabilities and limitations of the instrument are described. A brief account of available analysis software is also provided.Comment: Accepted for publication in JA