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                <text>Ecology&#13;
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Salamanders&#13;
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                <text>&lt;span&gt;Copyright&lt;/span&gt;&lt;span&gt; © 2021 Molnar. This is an open-access article distributed under the terms of the &lt;/span&gt;&lt;a href="http://creativecommons.org/licenses/by/4.0/" target="_blank" rel="noreferrer noopener"&gt;Creative Commons Attribution License (CC BY)&lt;/a&gt;&lt;span&gt;. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.&lt;/span&gt;</text>
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                <text>The size and shape of articular cartilage in the limbs of extant vertebrates are highly variable, yet they are critical for understanding joint and limb function in an evolutionary context. For example, inferences about unpreserved articular cartilage in early tetrapods have implications for how limb length, joint range of motion, and muscle leverage changed over the tetrapod water-land transition. Extant salamanders, which are often used as functional models for early limbed vertebrates, have much thicker articular cartilage than most vertebrate groups, but the exact proportion of cartilage and how it varies across salamander species is unknown. I aimed to quantify this variation in a sample of 13 salamanders representing a broad range of sizes, modes of life, and genera. Using contrast-enhanced micro-CT, cartilage dimensions and bone length were measured non-destructively in the humerus, radius, ulna, femur, tibia, and fibula of each specimen. Cartilage correction factors were calculated as the combined thickness of the proximal and distal cartilages divided by the length of the bony shaft. Articular cartilage added about 30% to the length of the long bones on average. Cartilage was significantly thicker in aquatic salamanders (42 ± 14% in the humerus and 35 ± 8 in the femur) than in terrestrial salamanders (21 ± 7% in both humerus and femur). There was no consistent relationship between relative cartilage thickness and body size or phylogenetic relatedness. In addition to contributing to limb length, cartilage caps increased the width and breadth of the epiphyses by amounts that varied widely across taxa. To predict the effect of salamander-like cartilage correction factors on muscle leverage, a simplified model of the hindlimb of the Devonian stem tetrapod Acanthostega was built. In this model, the lever arms of muscles that cross the hip at an oblique angle to the femur was increased by up to six centimeters. Future reconstructions of osteological range of motion and muscle leverage in stem tetrapods and stem amphibians can be made more rigorous by explicitly considering the possible effects of unpreserved cartilage and justifying assumptions based on available data from extant taxa, including aquatic and terrestrial salamanders.</text>
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                <text>&lt;span&gt;Molnar, J. L. (2021). Variation in Articular Cartilage Thickness Among Extant Salamanders and Implications for Limb Function in Stem Tetrapods. In Frontiers in Ecology and Evolution (Vol. 9). Frontiers Media SA. &lt;a href="https://doi.org/10.3389/fevo.2021.671006"&gt;https://doi.org/10.3389/fevo.2021.671006&lt;/a&gt;&lt;/span&gt;</text>
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                <text>Evolution, Homology, and Development of Tetrapod Limb Muscles</text>
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                <text>Biology &#13;
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Evolution Development&#13;
Differentiation&#13;
Homology&#13;
Muscle&#13;
Muscle reconstruction&#13;
Phylogeny</text>
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                <text>© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).</text>
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                <text>Diversity, Volume 13, Issue 8, August 2021, page 393</text>
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                <text>Since the early 1900s, researchers have attempted to unravel the origin and evolution of tetrapod limb muscles using a combination of comparative anatomy, phylogeny, and development. The methods for reconstructing soft tissues in extinct animals have been refined over time as our ability to determine muscle homology and phylogenetic relationships between tetrapods has improved. Since many muscles do not leave osteological correlates, muscle reconstruction in extinct animals is largely based on anatomy and development in extant animals. While muscle anatomy in extant tetrapods is quite conservative, the homologies of certain muscles between taxonomic groups are still uncertain. Comparative developmental studies can help to resolve these controversies, as well as revealing general patterns of muscle morphogenesis across tetrapod groups. We review the methods, results, and controversies in the muscle reconstructions of early members of the amniote, mammalian, and lissamphibian lineages, including recent attempts to reconstruct limb muscles in members of the tetrapod stem group. We also review the contribution of recent comparative developmental studies toward understanding the evolution of tetrapod limb muscles, including morphogenic gradients, the origin of paired fins, and the evolution of morphological complexity. Finally, we discuss the role of broad, comparative myological studies as part of an integrative research program on vertebrate evolutionary biology.</text>
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                <text>Molnar, J. L., &amp; Diogo, R. (2021). Evolution, Homology, and Development of Tetrapod Limb Muscles. In Diversity (Vol. 13, Issue 8, p. 393). MDPI AG. https://doi.org/10.3390/d13080393</text>
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                <text>Ecology&#13;
Evolution&#13;
Amniote&#13;
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Soft tissue reconstruction&#13;
Terrestriality&#13;
Tetrapod</text>
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                <text>&lt;span&gt;Copyright&lt;/span&gt;&lt;span&gt; © 2022 Molnar, Diogo, Boisvert and Werneburg. This is an open-access article distributed under the terms of the &lt;/span&gt;&lt;a href="http://creativecommons.org/licenses/by/4.0/" target="_blank" rel="noreferrer noopener"&gt;Creative Commons Attribution License (CC BY)&lt;/a&gt;&lt;span&gt;. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.&lt;br /&gt;&lt;/span&gt;</text>
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                <text>&lt;i&gt;Frontiers in Ecology and Evolution&lt;/i&gt;&lt;span&gt;, Volume 10, July 2022&lt;/span&gt;</text>
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                <text>Thanks to new methods of modeling and analysis, we are discovering much more about movement, sensation, and feeding in animals that span the tetrapod water-land transition and the origin of amniotes. As investigations of function in extinct animals become more complex and rigorous, the need to take soft tissues into account becomes more pressing. For example, biomechanical simulations of locomotion in early tetrapods rely on assumptions about their muscles and cartilages that come from living animals. Thus, the drive to learn more about our ancient relatives leads us to ask new questions about the relationships between hard and soft tissues over development and evolution. How did early land vertebrates transition from aquatic to terrestrial feeding? How did muscle anatomy and development change during the transformation from fins to limbs in tetrapods and with the loss of metamorphosis in amniotes? In this Research Topic, researchers approach these questions using fossils, biomechanical models, observation of living animals, and new imaging modalities that allow us to view embryonic development and adult anatomy in unprecedented detail.</text>
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                <text>&lt;span&gt;Molnar, J. L., Diogo, R., Boisvert, C. A., &amp;amp; Werneburg, I. (2022). Editorial: Tetrapod water-land transition: Reconstructing soft tissue anatomy and function. In Frontiers in Ecology and Evolution (Vol. 10). Frontiers Media SA. &lt;a href="https://doi.org/10.3389/fevo.2022.968979"&gt;https://doi.org/10.3389/fevo.2022.968979&lt;/a&gt;&lt;/span&gt;</text>
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                <text>Regionalization of the vertebral column can help animals adapt to different kinds of locomotion, including arboreal locomotion. Although functional axial regionalization has been described in both chameleons and arboreal mammals, no morphological basis for this functional regionalization in chameleons has been proposed. However, recent studies have described regionalization in the presacral vertebral column of other extant squamates. To investigate possible morphological regionalization in the vertebral column of chameleons, we took morphometric measurements from the presacral vertebrae of 28 chameleon species representing all extant chameleon genera, both fully arboreal and ground-dwelling, and performed comparative analyses. Our results support chameleons exhibiting three or four presacral morphological regions that correspond closely to those in other sauropsids, but we detected evolutionary shifts in vertebral traits occurring in only arboreal chameleons. Specifically, the anterior dorsal region in arboreal chameleons has more vertically oriented zygapophyseal joints, predicting decreased mediolateral flexibility. This shift is functionally significant because stiffening of the anterior thoracic vertebral column has been proposed to help bridge gaps between supports in primates. Thus, specialization of existing morphological regions in the vertebral column of chameleons may have played an important role in the evolution of extreme arboreal locomotion, paralleling the adaptations of arboreal primates.</text>
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Kallmann Syndrome genetics metabolism&#13;
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                <text>Kallmann syndrome (KS) is a congenital disorder characterized by idiopathic hypogonadotropic hypogonadism and olfactory dysfunction. KS is linked to variants in &gt;34 genes, which are scattered across the human genome and show disparate biological functions. Although the genetic basis of KS is well studied, the mechanisms by which disruptions of these diverse genes cause the same outcome of KS are not fully understood. Here we show that disruptions of KS-linked genes affect the same biological processes, indicating convergent molecular mechanisms underlying KS. We carried out machine learning-based predictions and found that KS-linked mutations in heparan sulfate 6-O-sulfotransferase 1 (HS6ST1) are likely loss-of-function mutations. We next disrupted Hs6st1 and another KS-linked gene, fibroblast growth factor receptor 1 (Fgfr1), in mouse neuronal cells and measured transcriptome changes using RNA sequencing. We found that disruptions of Hs6st1 and Fgfr1 altered genes in the same biological processes, including the upregulation of genes in extracellular pathways and the downregulation of genes in chromatin pathways. Moreover, we performed genomics and bioinformatics analyses and found that Hs6st1 and Fgfr1 regulate gene transcription likely via the transcription factor Sox9/Sox10 and the chromatin regulator Chd7, which are also associated with KS. Together, our results demonstrate how different KS-linked genes work coordinately in a convergent signaling pathway to regulate the same biological processes, thus providing new insights into KS.</text>
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                <text>&lt;em&gt;Human Molecular Genetics&lt;/em&gt;, Volume 31, Issue 24, December 2022, pages 4207-4216</text>
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                <text>&lt;span&gt;Moon, S., &amp;amp; Zhao, Y.-T. (2022). Convergent biological pathways underlying the Kallmann syndrome-linked genes Hs6st1 and Fgfr1. In Human Molecular Genetics (Vol. 31, Issue 24, pp. 4207–4216). Oxford University Press (OUP). &lt;a href="https://doi.org/10.1093/hmg/ddac172"&gt;https://doi.org/10.1093/hmg/ddac172&lt;/a&gt;&lt;/span&gt;</text>
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                <text>Recursive splicing (RS) is a splicing mechanism to remove long introns from messenger RNA precursors of long genes. Compared to the hundreds of RS events identified in humans and drosophila, only ten RS events have been reported in mice. To further investigate RS in mice, we analyzed RS in the mouse brain, a tissue that is enriched in the expression of long genes. We found that nuclear total RNA sequencing is an efficient approach to investigate RS events. We analyzed 1.15 billion uniquely mapped reads from the nuclear total RNA sequencing data in the mouse cerebral cortex. Unexpectedly, we only identified 20 RS sites, suggesting that RS is a rare event in the mouse brain. We also identified that RS is constitutive between excitatory and inhibitory neurons and between sexes in the mouse cerebral cortex. In addition, we found that the primary sequence context is associated with RS splicing intermediates and distinguishes RS AGGT site from non-RS AGGT sites, indicating the importance of the primary sequence context in RS sites. Moreover, we discovered that cryptic exons may use an RS-like mechanism for splicing. Overall, we provide novel findings about RS in long genes in the mouse brain. </text>
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                <text>&lt;em&gt;PLOS ONE&lt;/em&gt;, Volume 17, Issue 1, January 2022, page e0263082</text>
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                <text>&lt;span&gt;© 2022 Moon, Zhao. This is an open access article distributed under the terms of the &lt;/span&gt;&lt;a href="http://creativecommons.org/licenses/by/4.0/"&gt;Creative Commons Attribution License&lt;/a&gt;&lt;span&gt;, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.&lt;/span&gt;</text>
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                <text>&lt;span&gt;Moon, S., &amp;amp; Zhao, Y.-T. (2022). Recursive splicing is a rare event in the mouse brain. In A. F. Palazzo (Ed.), PLOS ONE (Vol. 17, Issue 1, p. e0263082). Public Library of Science (PLoS). &lt;a href="https://doi.org/10.1371/journal.pone.0263082"&gt;https://doi.org/10.1371/journal.pone.0263082&lt;/a&gt;&lt;/span&gt;</text>
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