Biology subjects

Cano, A.

Publications and source records attributed to Cano, A..

8 recordsLinked to original sources

bioRxiv2026

Progranulin haploinsufficiency remodels the cerebral microvasculature and neurovascular unit

Progranulin (PGRN) deficiency is a major genetic cause of frontotemporal dementia (FTD), yet its impact on cerebrovascular function remains understudied. Here, we show that PGRN deficiency contributes to cerebral microvascular perfusion and induces alterations within the neurovascular unit. In vivo two-photon imaging revealed increased capillary stalling and in cerebral blood flow (CBF), driven in part by increased leucocyte-capillary interactions and elevated endothelial ICAM-1 expression. Transcriptomic profiling of isolated cerebral microvessels demonstrated coordinated upregulation of immune and extracellular matrix pathways alongside suppression of angiogenic and stress-response programs, indicative of endothelial activation. Cross-species analyses identified partial conservation of these vascular signatures in endothelial cells from human FTD-GRN patients, associated with dysregulated angiogenic and inflammatory signaling. Despite altered tight junction organization and reduced solute carrier transporter expression, blood-brain barrier (BBB) permeability remained largely intact, suggesting functional rather than structural BBB disruption, as well as. These vascular changes were accompanied by broad alterations in the morphology of astrocytes, pericytes, and microglial cells. Here we determined a novel role for progranulin in cerebrovascular homeostasis and established microvascular dysfunction as a key driver of FTD-GRN pathophysiology.

neuroscience↗

bioRxiv2024

Early Cretaceous Origin and Evolutionary History of Palms (Arecaceae) inferred from 1,033 Nuclear Genes and a New Synthesis of Fossil Evidence

AO_SCPLOWBSTRACTC_SCPLOWTropical rainforests are home to almost half of all known plant diversity, yet a shortfall in tropical plant phylogenetic hypotheses is hindering our understanding of how rainforests have formed and adapted to past global changes. Phylogenetic and historical biogeographic evidence from key rainforest lineages, including palms (Arecaceae), are required to illuminate the history of these ecosystems. However, our current understanding of the palm tree of life is based on uneven sampling of data from the plastid and nuclear genome, and numerous palm genera and palm fossils have been described or revised over the past decade, casting doubt on many palm relationships, ages and ancestral ranges inferred in previous studies. Here, we infer the phylogenetic relationships of all palm genera based on data from 1,033 nuclear genes generated using target sequence capture. Our palm tree of life is highly resolved and supported. Remaining areas of ambiguity reflect the complex dynamics of palm evolution, including many rapid diversification events in subfamily Arecoideae and putative cases of ancient reticulation throughout the family. We review the phylogenetic placement and age of hundreds of palm fossils and use a vetted selection to estimate divergence times and ancestral ranges for all palm genera. We show that the family is older than previously thought, likely first diversifying in the Early Cretaceous in Laurasia, and that three quarters of the genera had originated by the Oligocene. The early spread of palms across the world involved at least 40 long-distance dispersals across oceanic gaps. Dispersals away from northern latitudes vastly outnumber dispersals into these latitudes, consistent with the ancient affinity of palms for megathermal climates, and suggesting that global cooling during the Oligocene was a major constraint on early palm distribution. Our dated phylogenomic tree and curated fossil dataset provide a new foundation for evolutionary studies on palms, opening the door to deeper research on the rainforest biome in which they thrive.

evolutionary biology↗

bioRxiv2022

Food recognition in a blood-feeding insect: characterization of the pharyngeal taste organ

BackgroundObligate blood-feeding insects obtain the nutrients and water necessary to ensure survival from the vertebrate blood. The internal taste sensilla, situated in the pharynx, evaluate the suitability of the ingested food. Here, through multiple approaches, we characterized the pharyngeal organ (PO) of the hematophagous kissing bug Rhodnius prolixus to determine its role in food assessment. The PO, located antero-dorsally in the pharynx, comprises 8 taste sensilla that become bathed with the incoming blood. ResultsWe showed that these taste sensilla house gustatory receptor neurons projecting their axons through the labral nerves to reach the subesophageal zone in the brain. We found that these neurons are electrically activated by relevant appetitive and aversive gustatory stimuli such as NaCl, ATP and caffeine. Using RNA-Seq, we examined the expression of sensory-related gene families in the PO. We identified gustatory receptors, ionotropic receptors, transient receptor potential channels, pickpocket channels, opsins, takeouts, neuropeptide precursors, neuropeptide receptors and biogenic amine receptors. RNA interference assays demonstrated that the pickpocket channel Rproppk014276 is necessary for salt detection during feeding. ConclusionWe provide evidence of the role of the pharyngeal organ in food evaluation. This work shows the first comprehensive characterization of a pharyngeal taste organ in a hematophagous insect.

neuroscience↗

bioRxiv2022

Mapping of the Classical Mutation rosette Highlights a Role for Calcium in Wound-induced Rooting

Removal of the root system induces the formation of new roots from the remaining shoot. This process is primarily controlled by the phytohormone auxin which interacts with other signals in a yet unresolved manner. Here, we study the classical tomato mutation rosette (ro) which lacks shoot-borne roots. ro plants were severely inhibited in the formation of wound-induced roots and have reduced rates of auxin transport. We mapped ro to the tomato ortholog of the Arabidopsis thaliana BIG and the mammalians UBR4/p600. RO/BIG is a large protein of unknown biochemical function. In A. thaliana, BIG was implicated in the regulation of auxin transport and calcium homeostasis. We show that exogenous calcium inhibits wound-induced root formation in both tomato and A. thaliana ro/big mutants. Exogenous calcium antagonized the root-promoting effects of the auxin IAA, but not of 2,4-D, an auxin analog that is not recognized by the polar transport machinery, and accumulation of the auxin transporter PIN1 was sensitive to calcium levels in the ro/big mutants. Consistent with a role for calcium in mediating auxin transport, both ro/big mutants and calcium-treated wild-type plants were hypersensitive to treatment with polar auxin transport inhibitors. Subcellular localization of BIG suggests that like its mammalian ortholog, it is associated with the endoplasmic reticulum (ER). Analysis of subcellular morphology revealed that ro/big mutants exhibited disruption in cytoplasmic streaming. We suggest that RO/BIG maintain auxin flow by stabilizing PIN membrane localization, possibly by attenuating the inhibitory effect of Ca2+ on cytoplasmic streaming.

plant biology↗

bioRxiv2021

The colonial legacy of herbaria

Herbarium collections shape our understanding of the worlds flora and are crucial for addressing global change and biodiversity conservation. The formation of such natural history collections, however, are not free from sociopolitical issues of immediate relevance. Despite increasing efforts addressing issues of representation and colonialism in natural history collections, herbaria have received comparatively less attention. While it has been noted that the majority of plant specimens are housed in the global North, the extent of this disparity has not been rigorously quantified to date. Here, by analyzing over 85 million specimen records and surveying herbaria across the globe, we assess the colonial legacy of botanical collections and how we may move towards a more inclusive future. We demonstrate that colonial exploitation has contributed to an inverse relationship between where plant biodiversity exists in nature and where it is housed in herbaria. Such disparities persist in herbaria across physical and digital realms despite overt colonialism having ended over half a century ago, suggesting ongoing digitization and decolonization efforts have yet to alleviate colonial-era discrepancies. We emphasize the need for acknowledging the inconvenient history of herbarium collections and the implementation of a more equitable, global paradigm for their collection, curation, and use.

ecology↗

bioRxiv2021

Salty surfaces deter feeding in a blood-sucking disease vector

Salts are essential nutrients required for many physiological processes, and deficient or excessive salt results in adverse health problems. Taste is the ultimate sensory modality involved in resource quality assessment, resulting in acceptance or rejection. Here, we show that detection of high-salt substrates by a salt-sensitive antennal gustatory receptor neuron, S1-GRN, results in feeding avoidance in the hematophagous bug Rhodnius prolixus. Knock-down of two antennal-expressed amiloride-sensitive pickpocket channel receptors (PPKs; RproPPK014276 and RproPPK28) using RNA interference, prevents avoidance of bugs to high-salt substrates. Tracing antennal GRNs to the central nervous system reveals the antennal lobes as a gustatory processing center. The identification of the gustatory basis of high-salt detection in a blood feeder provides novel targets to prevent biting and feeding, as well as to promote substrate avoidance in a relevant disease vector. Significance StatementDetection of aversive gustatory stimuli induces avoidance responses in animals. Avoidance acquires particular interest if it reduces the biting rates of blood-feeding insects of medical relevance. Here we describe the molecular and physiological basis of high-salt detection in the blood-sucking disease vector Rhodnius prolixus. We show that detection of high-salt substrates through two PPK receptors expressed in an antennal gustatory receptor neuron produces feeding avoidance. Understanding these gustatory-driven aversive responses allows the hitherto overlooked use of gustatory molecules as a complement to known olfactory repellents.

physiology↗

bioRxiv2019

Perception of aversive stimuli of different gustatory modalities in an haematophagous insect, Rhodnius prolixus.

Sensory aversion is an essential link for avoiding potential dangers. Here, we studied the chemical perception of aversive compounds of different gustatory modalities (salty and bitter) in the haematophagous kissing bug, Rhodnius prolixus. Over a walking arena, insects preferred a substrate embedded with 0.3 M NaCl or KCl rather than with distilled water. Same salts were avoided when prepared at 1 M. When NaCl and KCl were confronted, no preferences were evinced by insects. A pre-exposure to amiloride interfered with the repellency of NaCl and KCl equally, suggesting that amiloride-sensitive receptors are involved in the detection of both salts. Discriminative experiments were then performed to determine if R. prolixus can distinguish between these salts. An aversive operant conditioning involving either NaCl or KCl modulated the repellency of the conditioned salt, but also of the novel salt. A chemical pre-exposure to the salts did not to modify their repellency levels. When we crossed gustatory modalities by confronting NaCl to caffeine (i.e. a bitter stimulus) no innate preferences were evinced. Aversive operant conditionings with either NaCl or Caf rendered unspecific changes in the repellency of both compounds. A chemical pre-exposure to Caf modulated the response to Caf but not to NaCl, suggesting the existence of two independent neural pathways for the detection of salts and bitter compounds. Overall results suggest that R. prolixus cannot distinguish between NaCl and KCl but can distinguish between NaCl and Caf and generalizes the response between these two aversive stimuli of different gustatory modality.\n\nSummary statementKissing-bugs use contact chemo-perception to avoid aversive substrates. They can sensory distinguish between salty (sodium chloride) and bitter (caffeine) tastes, but not between different salts (sodium and potassium chloride).

animal behavior and cognition↗

bioRxiv2018

A structural mechanism for directing inverse agonism of PPARγ

Small chemical modifications can have significant effects on ligand efficacy and receptor activity, but the underlying structural mechanisms can be difficult to predict from static crystal structures alone. Here we show how a simple phenyl-to-pyridyl substitution between two common covalent orthosteric ligands targeting peroxisome proliferator-activated receptor gamma (PPAR{gamma}) converts a transcriptionally neutral antagonist (GW9662) into an inverse agonist (T0070907). X-ray crystallography, molecular dynamics simulations, and mutagenesis coupled to activity assays reveal a water-mediated hydrogen bond network linking the T0070907 pyridyl group to Arg288 that is essential for inverse agonism. NMR spectroscopy reveals that PPAR{gamma} exchanges between two long-lived conformations when bound to T0070907 but not GW9662, including a conformation that prepopulates a corepressor-bound state, priming PPAR{gamma} for high affinity corepressor binding. Our findings demonstrate that ligand engagement of Arg288 may provide new routes for developing PPAR{gamma} inverse agonist.

biochemistry↗