Biology subjects

Palomino, S.

Publications and source records attributed to Palomino, S..

4 recordsLinked to original sources

bioRxiv2026

Prey-specific toxins provide broad venom activity in cephalopods

Cephalopods are among the oceans most sophisticated predators that use camouflage, complex behaviors, and venom to subdue a wide range of prey. However, the functional role of venom across diverse prey remains poorly understood, particularly whether cephalopods deploy venom to capture fish. Through comprehensive transcriptomic profiling of venom glands, we identify toxins with molecular signatures of prey-specific adaptation, including a previously unrecognized family of peptide toxins, octotensins, that evolved through convergent evolution to mimic the vertebrate hormone neurotensin. Functional assays and cryo-electron microscopy demonstrate that octotensins potently activate fish and human neurotensin receptor 1, engage this target in a near-identical manner to the chordate hormone, and induce acute hypotension in rodents. Together, our findings demonstrate that cephalopods achieve broad venom activity through phylum-specific toxins, including those targeting fish, revealing an evolutionary strategy by which generalist predators can capture phylogenetically diverse prey. One-Sentence SummaryCephalopod venom comprises prey-specific toxins, including neurotensin-mimicking peptides that target fish.

systems biology↗

bioRxiv2026

Mimics of the chordate gut-brain hormone neurotensin in parasitic intestinal hookworms

Hookworms of the family Ancylostomatidae are intestinal parasites that infect hundreds of millions of people worldwide, contributing to malnutrition, anemia, and impaired development. While hookworms are known to secrete immunomodulatory molecules to evade host defenses, it has been unclear whether they also exploit host hormonal signaling. Here, we identify a previously unrecognized family of hookworm peptides, which we term ancylotensins. Ancylotensins share strong sequence similarity with the chordate hormone neurotensin, a key regulator of metabolism, gut-brain communication, and intestinal function. In vitro pharmacological assays, ex vivo gut contractility studies, and cryo-electron microscopy demonstrate that ancylotensins closely replicate both the structural and functional properties of mammalian neurotensin to modulate gut function. Furthermore, ancylotensins do not share common ancestry with chordate neurotensin and instead evolved independently via convergent evolution. These findings reveal the existence of gut peptide mimicry as a mechanism by which intestinal parasites can manipulate host physiology.

biochemistry↗

bioRxiv2025

Expansion of OSMR expression and signaling in the human dorsal root ganglion links OSM to neuropathic pain

RNA sequencing studies on human dorsal root ganglion (hDRG) from patients suffering from neuropathic pain show upregulation of OSM, linking this IL-6 family cytokine to pain disorders. In mice, however, OSM signaling causes itch behaviors through a direct effect on its cognate receptor expressed uniquely by pruriceptive sensory neurons. We hypothesized that an expansion in function of OSM-OSM receptor (OSMR) in sensory disorders in humans could be explained by species differences in receptor expression and signaling. Our in situ hybridization and immunohistochemical findings demonstrate broad expression of OSMR in DRG nociceptors and afferent fibers innervating the superficial and deep skin of humans. In patch-clamp electrophysiology, OSM directly activates human sensory neurons engaging MAPK signaling to promote action potential firing. Using CRISPR editing we show that OSM activation of MAPK signaling is dependent on OSMR and not LIFR in hDRG. Bulk, single-nuclei, and single-cell RNA-seq of OSM-treated hDRG cultures reveal expansive similarities in the transcriptomic signature observed in pain DRGs from neuropathic patients, indicating that OSM alone can orchestrate transcriptomic signatures associated with pain. We conclude that OSM-OSMR signaling via MAPKs is a critical signaling factor for DRG plasticity that may underlie neuropathic pain in patients.

neuroscience↗

bioRxiv2022

An Atlas of Cells in the Human Tonsil

Palatine tonsils are secondary lymphoid organs representing the first line of immunological defense against inhaled or ingested pathogens. Here, we present a comprehensive census of cell types forming the human tonsil by applying single-cell transcriptome, epigenome, proteome and adaptive immune repertoire sequencing as well as spatial transcriptomics, resulting in an atlas of >357,000 cells. We provide a glossary of 121 annotated cell types and states, and disentangle gene regulatory mechanisms that drive cells through specialized lineage trajectories. Exemplarily, we stratify multiple tonsil-resident myeloid slancyte subtypes, establish a distant BCL6 superenhancer as locally active in both follicle-associated T and B cells, and describe SIX5 as a potentially novel transcriptional regulator of plasma cell maturation. Further, our atlas is a reference map to understand alterations observed in disease. Here, we discover immune-phenotype plasticity in tumoral cells and microenvironment shifts of mantle cell lymphomas (MCL). To facilitate such reference-based analysis, we develop HCATonsilData and SLOcatoR, a computational framework that provides programmatic and modular access to our dataset; and allows the straightforward annotation of future single-cell profiles from secondary lymphoid organs.

immunology↗