Newsfeeds

PLOS Biology: New Articles

  • Does oxygen limitation set thermal limits in aquatic ectotherms?

    by Diana Madeira

    Thermal tolerance determines winners and losers in a warming world. Oxygen limitation has been the primary hypothesis for the mechanistic basis of thermal tolerance. A new study in PLOS Biology suggests otherwise, reigniting debate on what truly sets thermal limits. Oxygen limitation is thought to represent a key mechanism underlying thermal tolerance. This primer discusses how a recent PLOS Biology article challenges this idea, by showing minimal protective effects of oxygen supersaturation in aquatic ectotherms exposed to heat stress.

  • When the brain talks back to the eye

    by Dominic Gonschorek, Thomas Euler

    The state of our brain shapes what we see, but how early in the visual system does this start? A new study in PLOS Biology shows that brain state-dependent release of histamine modulates the very first stage of vision in the retina. The state of our brain shapes what we see, but how early in the visual system does this start? This Primer explores a new PLOS Biology study which shows that brain state-dependent release of histamine modulates the very first stage of vision – the retina.

  • Environmental noise-induced changes to the IC-SNc circuit promotes motor deficits and neuronal vulnerability in a mouse model of Parkinson’s Disease

    by Chi Cui, Yibo Yao, Yulong Shi, Jie Lei, Kun Ren, Kexing Wan, Tongxia Li, Gangan Luo, Qian Xu, Ming Li, Xiang Peng, Xueke Yang, Jian Yang, Junsong Du, Sitong Chen, Bo Tian, Pei Zhang

    Emerging clinical evidence suggests a link between environmental noise and the severity of Parkinson’s disease (PD). However, the effects of high-decibel noise exposure on PD and its underlying mechanisms remain unclear. In this study, we demonstrate that acute noise exposure induces reversible motor deficits in subacute low-dose 6-hydroxydopamine (6-OHDA) mice, a model of presymptomatic early-stage PD, while chronic noise exposure results in irreversible motor deficits and significant loss of substantia nigra compacta (SNc) dopaminergic (DA) neurons. Additionally, noise exposure activates the inferior colliculus (IC), which sends monosynaptic projections to SNcDA neurons. Optogenetic or chemogenetic bidirectional activation or inhibition of the IC-SNc circuit can mimic or reverse the 6-OHDA vulnerability caused by acute or chronic noise exposure. Mechanistically, noise exposure and IC-SNc circuit activation down-regulate vesicular monoamine transporter 2 (VMAT2) in the SNc, and overexpression of VMAT2 in IC-innervated SNcDA neurons ameliorates noise exposure-induced 6-OHDA vulnerability. Our findings uncover a previously unappreciated role of the IC-SNc circuit in early-stage PD mice in response to environmental noise, which has significance for preventing the onset and progression of PD and highlights the need for environmental harmony to reduce neurodegeneration.

  • Foxi2 and Sox3 are master transcription regulators that control ectoderm germ layer specification in <i>Xenopus</i>

    by Clark L. Hendrickson, Ira L. Blitz, Amina Hussein, Kitt D. Paraiso, Jin S. Cho, Michael W. Klymkowsky, Matthew J. Kofron, Ken W. Y. Cho

    Germ layer specification represents a critical transition where pluripotent cells acquire lineage-specific identities. We identify the maternal transcription factors Foxi2 and Sox3 to be pivotal master regulators of ectodermal germ layer specification in Xenopus. Ectopic co-expression of Foxi2 and Sox3 in prospective endodermal tissue induces the expression of ectodermal markers while suppressing mesendodermal markers. Transcriptomics analyses reveal that Foxi2 and Sox3 jointly and independently regulate hundreds of ectodermal target genes. During early cleavage stages, Foxi2 and Sox3 pre-bind to key cis-regulatory modules (CRMs), marking sites that later recruit Ep300 and facilitate H3K27ac deposition, thereby shaping the epigenetic landscape of the ectodermal genome. These CRMs are highly enriched within ectoderm-specific super-enhancers (SEs). Our findings highlight the pivotal role of ectodermal SE-associated CRMs in precise and robust ectodermal gene activation, establishing Foxi2 and Sox3 as central architects of ectodermal lineage specification.

  • Zebrafish fast muscle contractions avoid the mammalian requirement for voltage-gated Na<sup>+</sup> channels

    by Léa Demesmay, Romane Idoux, Christine Berthier, Claire Bernat, Léon Espinosa, Vincent Jacquemond, Frédéric Brunet, Angel Maunier-Mercier, Philippe Lory, Sophie Nicole, Bruno Allard

    Fast skeletal muscle fibers from zebrafish share a number of functional properties with mammalian twitch muscle fibers, making this vertebrate a precious model to investigate the pathophysiology of neuromuscular disorders. We previously reported that action potentials (APs) from zebrafish fast fibers exhibit low amplitude and require unusually strong negative resting membrane voltage levels to be elicited. In this study, using voltage-clamp and current-clamp techniques, we explored the properties of voltage-gated Na+ channels (NaV) responsible for initiation and propagation of AP in isolated adult zebrafish fast skeletal muscle fibers and compared them to mouse fast-twitch muscle fibers using the same experimental conditions. We found that kinetics of activation and inactivation of NaV were faster in zebrafish fibers and, overall, that the voltage-dependence of inactivation was shifted by 25 mV toward negative voltages as compared to mouse fibers, yielding a mean half-inactivation potential of −90 mV. In agreement with these findings, recording of APs at various resting membrane potentials indicated that APs vanished for resting membrane potentials less negative than −80 mV in zebrafish, whereas APs could still be elicited from resting membrane potentials as low as −60 mV in mice. In addition, Ca2+ transients induced by field stimulation were insensitive to Na+ current blockade in zebrafish but not in mouse fibers. Fluorescence labeling of nicotinic acetylcholine receptors showed that zebrafish fast fibers were multi-innervated with a mean distance between extra-synaptic sarcolemma and motor endplates of 14 µm, expected to lead to negligible attenuation of depolarization propagated from endplates. Finally, knock out of the two genes encoding pore-forming NaV subunits in zebrafish muscles did not induce any change in locomotion and escape behavior of the animals. Taken together, these data question the role of NaV and the occurrence of APs in zebrafish fast muscle.