Could venom-derived therapeutics resolve treatment resistance in refractory EAC?

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  Could venom-derived therapeutics resolve treatment resistance in refractory EAC? Abstract The incidence of esophageal adenocarcinoma is rising in Western countries. Despite advances in chemotherapy and immunotherapy, the prognosis remains poor, with an overall 5-year survival rate below 15%. A major challenge is the cancer’s poor and often unpredictable response to current treatments. Animal venoms represent a promising yet underexplored source of therapeutic agents, offering millions of structurally diverse and highly potent bioactive peptides that can modulate a wide array of molecular targets. However, only a small fraction of these peptides has been pharmacologically characterized. This review presents the therapeutic potential of venom-derived peptides in cancer treatment, summarizes the role of ion channels in esophageal adenocarcinoma (EAC), and discusses peptides targeting ion channels that may offer new opportunities for future EAC treatment. Freuville L, Matthys C, Gill...

The protamines of the noble false widow spider Steatoda nobilis provide an example of liquid-liquid phase separation chromatin transitions during spermiogenesis

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The protamines of the noble false widow spider Steatoda nobilis provide an example of liquid-liquid phase separation chromatin transitions during spermiogenesis

    Abstract

While there is extensive information about sperm nuclear basic proteins (SNBP) in vertebrates, there is very little information about Arthropoda by comparison. This paper aims to contribute to filling this gap by analyzing these proteins in the sperm of the noble false widow spider Steatoda nobilis (Order Araneae, Family Theridiidae). To this end, we have developed a protein extraction method that allows the extraction of cysteine-containing protamines suitable for the preparation and analysis of SNBPs from samples where the amount of starting tissue material is limited. We carried out top-down mass spectrometry sequencing and molecular phylogenetic analyses to characterize the protamines of S. nobilis and other spiders. We also used electron microscopy to analyze the chromatin organization of the sperm, and we found it to exhibit liquid-liquid phase spinodal decomposition during the late stages of spermiogenesis. These studies further our knowledge of the distribution of SNBPs within the animal kingdom and provide additional support for a proposed evolutionary origin of many protamines from a histone H1 (H5) replication-independent precursor.


The protamines of the noble false widow spider Steatoda nobilis provide an example of liquid-liquid phase separation chromatin transitions during spermiogenesis

Melissa R Leyden, Peter Michalik, Luciana Baruffaldi, Susheen Mahmood, Ladan Kalani, Donald F Hunt, Jose Maria Eirin-Lopez, Maydianne C.B. Andrade, Jeffrey Shabanowitz, Juan Ausió

bioRxiv 2024.06.04.597381; doi: https://doi.org/10.1101/2024.06.04.597381