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PLOS Biology: New Articles

  • Phylogenomic signatures of repeat-induced point mutations across the fungal kingdom

    by Thomas Badet, Daniel Croll

    Fungal genome sizes exhibit more than a 100-fold variation, largely driven by the expansion of repetitive sequences such as transposable elements (TEs). Silencing mechanisms targeting TEs at the epigenetic or transcript level have independently evolved in many lineages. In fungi, repeat-induced point mutation (RIP) targets TEs by recognizing repetitive sequences and inducing mutagenesis. However, the prevalence of RIP across the fungal kingdom and the fidelity of the canonical C-to-T mutation signatures remain unclear. In this study, we address these gaps by tracking shifts in genome architecture across the fungal kingdom. We find that a striking approximately 30-fold increase in genome size within a clade of leotiomycetes is associated with the absence of several RIP-related genes, suggesting a relaxation of genome defense mechanisms during this expansion. To track the impact of genome defenses, we designed a quantitative screen for RIP-like mutation signatures. The phylum of ascomycetes was unique in showing enrichment in mutation signatures in non-coding and repetitive sequences, consistent with a phylogenetically restricted occurrence of RIP-like genome defense systems. Then, we performed a phylogeny-aware association study to identify gene functions associated with RIP-like mutation signatures. We identified a zinc-finger protein as the strongest candidate underpinning a novel mechanism of genome defenses. Our findings reveal the multifaceted drivers of genome defense systems and their close ties to genome size evolution in fungi, particularly in lineages with evidence for recent RIP activity, highlighting how proximate molecular mechanisms can shape genome evolution on deep phylogenetic scales.

  • Combining gamma neuromodulation and robotic rehabilitation after a stroke restores parvalbumin interneuron dynamics and improves motor recovery in mice

    by Livia Vignozzi, Francesca Macchi, Elena Montagni, Maria Pasquini, Alessandra Martello, Antea Minetti, Éléa Coulomb, Anna Letizia Allegra Mascaro, Silvestro Micera, Matteo Caleo, Cristina Spalletti

    Stroke is a leading cause of long-term disability, frequently associated with persistent motor deficits. Gamma band oscillations, generated by synchronous discharge of parvalbumin-positive interneurons (PV-INs), are critically affected after stroke in humans and animals. Both gamma band and PV-INs play a key role in motor function, thus representing a promising target for poststroke neurorehabilitation. Noninvasive neuromodulatory approaches are considered a safe intervention and can be used for this purpose. Here, we present a novel, clinically relevant, noninvasive, and well-tolerated sub-acute treatment combining robotic rehabilitation with advanced neuromodulation techniques, validated in a mouse model of ischemic injury. During the sub-acute poststroke phase, we scored profound deficits in motor-related gamma band activity in the perilesional cortex. These deficits were accompanied by reduced PV-IN firing rates and increased functional connectivity, both at the perilesional and at the whole-cortex levels. Therefore, we tested the therapeutic potential of coupling robotic rehabilitation with optogenetic PV-IN-driven gamma band stimulation in a subacute poststroke phase during motor training to reinforce the efficacy of the treatment. Frequency-specific movement-related gamma band stimulation, when combined with physical training, significantly improved forelimb motor function. More importantly, by pairing robotic rehabilitation with a clinical-like noninvasive 40 Hz transcranial Alternating Current Stimulation, we achieved similar motor improvements mediated by the effective restoring of movement-related gamma band power, improvement of PV-IN maladaptive network dynamics, and increased PV-IN connections in premotor cortex. Our research introduces a new understanding of the role of parvalbumin-interneurons in poststroke impairment and recovery. These results highlight the synergistic potential of combining perilesional gamma band stimulation with robotic rehabilitation as a promising and realistic therapeutic approach for stroke patients.

  • A large-scale study across the avian clade identifies ecological drivers of neophobia

    by ManyBirds Project , Rachael Miller, Vedrana Šlipogor, Kai R. Caspar, Jimena Lois-Milevicich, Carl Soulsbury, Stephan A. Reber, Claudia Mettke-Hofmann, Megan Lambert, Benjamin J. Ashton, Alice M. I. Auersperg, Melissa Bateson, Solenne Belle, Boris Bilčík, Laura M. Biondi, Francesco Bonadonna, Desiree Brucks, Michael W. Butler, Samuel P. Caro, Marion Charrier, Tiffany Chatelin, Johnathan Ching, Nicola S. Clayton, Benjamin J. Cluver, Ella B. Cochran, Francesca Cornero, Emily Danby, Samara Danel, Martina Darwich, James R. Davies, Alicia de la Colina, Dominik Fischer, Ondřej Fišer, Florencia Foitzick, Edward C. Galluccio, Clara Garcia-Co, Elias Garcia-Pelegrin, Isabelle George, Kai-Philipp Gladow, Raúl O. Gómez, Anna Grewer, Katie Grice, Lauren M. Guillette, Devon C. Hallihan, Katie J. Harrington, Frauke Heer, Chloe Henry, Vladimira Hodova, Marisa Hoeschele, Cécilia Houdelier, Paula Ibáñez de Aldecoa, Oluwaseun Serah Iyasere, Yuka Kanemitsu, Mina Khodadadi, Duc Khong, Melanie G. Kimball, Ariana N. Klappert, Lucy N. Koch, Uta U. König von Borstel, Lubor Košt’ál, Anastasia Krasheninnikova, Lubica Kubikova, Connor T. Lambert, Daan W. Laméris, Courtenay G. Lampert, Oceane Larousse, Christine R. Lattin, Zhongqiu Li, Michael Lindenmeier, Delia A. Lister, Julia A. Mackenzie, Selina Mainz, Danna Masri, Jorg J. M. Massen, Laurenz Mohr, Wendt Müller, Paul M. Nealen, Andreas Nieder, Aurèle Novac, Nínive Paes Cavalcante, Kristina Pascual, Carla Pascual-Guàrdia, Ayushi Patel, Katarína Pichová, Cristina Pilenga, Laurent Prétôt, John L. Quinn, Elena Račevska, Juan C. Reboreda, Sam Reynolds, Amanda R. Ridley, Theresa Rössler, Francisco Ruiz-Raya, Marina Salas, Beatriz C. Saldanha, Sebastián M. Santiago, Nikola Schlöglová, Gia Seatriz, Eva Serrano-Davies, Eva G. Shair Ali, Janja Sirovnik, Zuzana Skalná, Katie E. Slocombe, Masayo Soma, Tiziana Srdoc, Stefan Stanescu, Michaela Syrová, Alex H. Taylor, Christopher N. Templeton, Karlie Thompson, Sandra Trigo, Camille A. Troisi, Utku Urhan, Maurice Valbert, Kees van Oers, Alberto Velando, Frederick Verbruggen, Jorrit W. Verkleij, Alizée Vernouillet, Jonas Verspeek, Petr Veselý, Auguste M. P. von Bayern, Eline Waalders, Benjamin A. Whittaker, Ella R. Williamson, Vanessa A. D. Wilson, Michelle A. Winfield, Neslihan Wittek, Karen K. L. Yeung, Jade A. Zanutto

    Neophobia, or aversion to novelty, is important for adaptability and survival as it influences the ways in which animals navigate risk and interact with their environments. Across individuals, species and other taxonomic levels, neophobia is known to vary considerably, but our understanding of the wider ecological drivers of neophobia is hampered by a lack of comparative multispecies studies using standardized methods. Here, we utilized the ManyBirds Project, a Big Team Science large-scale collaborative open science framework, to pool efforts and resources of 129 collaborators at 77 institutions from 24 countries worldwide across six continents. We examined both difference scores (between novel object test and control conditions) and raw data of latency to touch familiar food in the presence (test) and absence (control) of a novel object among 1,439 subjects from 136 bird species across 25 taxonomic orders incorporating lab, field, and zoo sites. We first demonstrated that consistent differences in neophobia existed among individuals, among species, and among other taxonomic levels in our dataset, rejecting the null hypothesis that neophobia is highly plastic at all taxonomic levels with no evidence for evolutionary divergence. We then tested for effects of ecological factors on neophobia, including diet, sociality, habitat, and range, while accounting for phylogeny. We found that (i) species with more specialist diets were more neophobic than those with more generalist diets, providing support for the Neophobia Threshold Hypothesis; (ii) migratory species were also more neophobic than nonmigratory species, which supports the Dangerous Niche Hypothesis. Our study shows that the evolution of avian neophobia has been shaped by ecological drivers and demonstrates the potential of Big Team Science to advance our understanding of animal behavior.

  • The superficial layers of the primary visual cortex create a saliency map that feeds forward to the parietal cortex

    by Chen Liu, Chengwen Liu, Laurentius Huber, Li Zhaoping, Peng Zhang

    A salient visual object with a distinct feature from the surrounding environment automatically captures attention. While the saliency signals have been found in many brain regions, their source remains highly controversial. Here, we investigated the neural origin of visual saliency using cortical layer-dependent functional magnetic resonance imaging (fMRI) of cerebral blood volume (CBV) at 7 Tesla. Behaviorally, human observers were better at detecting salient foreground bars with a larger orientation contrast from uniformly oriented background bars. Saliency-sensitive signals were strongest in the superficial layers of the primary visual cortex (V1) and in the middle layers of the intraparietal sulcus (IPS) of the parietal cortex. Layer-dependent effective connectivity revealed the transmission of saliency signals along the feedforward pathway from V1 to IPS. Furthermore, behavioral sensitivity to the foreground stimulus correlated significantly with the fMRI response in the superficial layers of V1. Our findings provide mesoscale evidence that a visual saliency map is created by iso-feature suppression through lateral inhibition in the superficial layers of V1, and then feeds forward to attentional control brain regions to guide attention and eye movements.

  • Hippocampal pyramidal cells of the CA1 region are not a major target of the thalamic nucleus reuniens

    by Lilya Andrianova, Paul J. Banks, Clair A. Booth, Erica S. Brady, Gabriella Margetts-Smith, Shivali Kohli, Jonathan Cavanagh, Zafar I. Bashir, Chris J. McBain, Michael T. Craig

    The prefrontal—hippocampal—entorhinal system is perhaps the most widely-studied circuit in cognitive and systems neuroscience, due to its role in supporting cognitive functions such as working memory and decision-making. Disrupted communication within this circuit is a key feature of disorders such as schizophrenia and dementia. Nucleus reuniens (NRe) is a midline thalamic nucleus that sits at the nexus of this circuit, linking these regions together. As there are no direct projections from prefrontal cortex to hippocampus (HPC), the accepted model is that the NRe mediates prefrontal drive of hippocampal activity, although these connections are poorly defined at the cellular and synaptic level. Using ex vivo optogenetics and electrophysiology in both mice and rats, alongside monosynaptic circuit-tracing, we sought to test the mechanisms through which NRe could drive hippocampal activity. Unexpectedly, we found no evidence that pyramidal cells in CA1 receive input from NRe, with midline thalamic input to HPC proper appearing selective for GABAergic interneurons. In other regions targeted by NRe, we found that pyramidal cells in prosubiculum and subiculum received synaptic inputs from NRe that were at least an order of magnitude weaker than those in prefrontal or entorhinal cortices. We conclude that, contrary to widely-held assumptions in the field, the hippocampal pyramidal cells are not a major target of NRe.