3,121 results on '"Lucas, R."'
Search Results
2. Effect of nuts on lipid profile and inflammatory biomarkers in atherosclerotic cardiovascular disease: a systematic review and meta-analysis of randomized controlled trials
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Bersch-Ferreira, Ângela C., Stein, Elana, Waclawovsky, Gustavo, da Silva, Lucas R., Machado, Rachel H. V., Weschenfelder, Camila, Figueiro, Mabel F., Suzumura, Erica A., Santos, Renato H. N., Duarte, Graziela Biude Silva, Rogero, Marcelo M., de Abreu-Silva, Erlon O., Cavalcanti, Alexandre B., and Marcadenti, Aline
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- 2024
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3. Short–term outcomes of heavyweight versus mediumweight synthetic mesh in a retrospective cohort of clean–contaminated and contaminated retromuscular ventral hernia repairs
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Ellis, Ryan C., Maskal, Sara M., Messer, Nir, Miller, Benjamin T., Petro, Clayton C., Prabhu, Ajita S., Rosen, Michael J., Zheng, Xinyan, and Beffa, Lucas R. A.
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- 2024
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4. Does selective intraoperative music reduce pain following abdominal wall reconstruction? A double-blind randomized controlled trial
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Maskal, Sara M., Gentle, Corey K., Ellis, Ryan C., Tu, Chao, Rosen, Michael J., Petro, Clayton C., Miller, Benjamin T., Beffa, Lucas R. A., Chang, Jenny H., Messer, Nir, Melland-Smith, Megan, Jeekel, Johannes, and Prabhu, Ajita S.
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- 2024
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5. Factors Associated with Erectile Dysfunction Among Older Gay Men
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Prieto, Lucas R., Shires, Deirdre A., and Xiong, Yuan
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- 2024
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6. Continuing benefits of the Montreal Protocol and protection of the stratospheric ozone layer for human health and the environment
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Madronich, S., Bernhard, G. H., Neale, P. J., Heikkilä, A., Andersen, M. P. Sulbæk, Andrady, A. L., Aucamp, P. J., Bais, A. F., Banaszak, A. T., Barnes, P. J., Bornman, J. F., Bruckman, L. S., Busquets, R., Chiodo, G., Häder, D.-P., Hanson, M. L., Hylander, S., Jansen, M. A. K., Lingham, G., Lucas, R. M., Calderon, R. Mackenzie, Olsen, C., Ossola, R., Pandey, K. K., Petropavlovskikh, I., Revell, L. E., Rhodes, L. E., Robinson, S. A., Robson, T. M., Rose, K. C., Schikowski, T., Solomon, K. R., Sulzberger, B., Wallington, T. J., Wang, Q.-W., Wängberg, S.-Å., White, C. C., Wilson, S. R., Zhu, L., and Neale, R. E.
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- 2024
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7. The association of permanent versus absorbable fixation on developing chronic post-herniorrhaphy groin pain in patients undergoing laparoscopic inguinal hernia repair
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Woo, Kimberly P., Ellis, Ryan C., Maskal, Sara M., Remulla, Daphne, Shukla, Priya, Rosen, Alexandra J., Wetzka, Isabella, Osei-Koomson, Wilhemina, Phillips, Sharon, Miller, Benjamin T., Beffa, Lucas R., Petro, Clayton C., Krpata, David M., Prabhu, Ajita S., Menzo, Emanuele Lo, and Rosen, Michael J.
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- 2024
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8. Describing Non-Binary People’s Encounters with the Healthcare System: A Qualitative Study in Catalonia (Spain)
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Gómez-Ibáñez, Rebeca, Leyva-Moral, Juan M., Cruzado-Reyes, Alexander, Platero, Lucas R., Granel, Nina, and Watson, Carolina E.
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- 2024
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9. Skeletal Muscle Spheroids as Building Blocks for Engineered Muscle Tissue
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Johnson, Nicholas, Filler, Andrea C, Sethi, Akash, Smith, Lucas R, and Leach, J Kent
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Engineering ,Biomedical Engineering ,Regenerative Medicine ,Musculoskeletal ,Animals ,Cattle ,Mice ,Tissue Engineering ,Spheroids ,Cellular ,Muscle ,Skeletal ,Cell Differentiation ,Alginates ,spheroids ,skeletal muscle ,bioprinting ,muscle engineering ,hydrogel ,Biomedical engineering - Abstract
Spheroids exhibit enhanced cell-cell interactions that facilitate improved survival and mimic the physiological cellular environment in vivo. Cell spheroids have been successfully used as building blocks for engineered tissues, yet the viability of this approach with skeletal muscle spheroids is poorly understood, particularly when incorporated into three-dimensional (3D) constructs. Bioprinting is a promising strategy to recapitulate the hierarchical organization of native tissue that is fundamental to its function. However, the influence of bioprinting on skeletal muscle cell spheroids and their function are yet to be interrogated. Using C2C12 mouse myoblasts and primary bovine muscle stem cells (MuSCs), we characterized spheroid formation as a function of duration and cell seeding density. We then investigated the potential of skeletal muscle spheroids entrapped in alginate bioink as tissue building blocks for bioprinting myogenic tissue. Both C2C12 and primary bovine MuSCs formed spheroids of similar sizes and remained viable after bioprinting. Spheroids of both cell types fused into larger tissue clusters over time within alginate and exhibited tissue formation comparable to monodisperse cells. Compared to monodisperse cells in alginate gels, C2C12 spheroids exhibited greater MyHC expression after 2 weeks, while cells within bovine MuSC spheroids displayed increased cell spreading. Both monodisperse and MuSC spheroids exhibited increased expression of genes denoting mid- and late-stage myogenic differentiation. Together, these data suggest that skeletal muscle spheroids have the potential for generating myogenic tissue via 3D bioprinting and reveal areas of research that could enhance myogenesis and myogenic differentiation in future studies.
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- 2024
10. Extreme Heterogeneity 2018: DOE ASCR Basic Research Needs Workshop on Extreme Heterogeneity
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Byna, Surendra, Vetter, Jeff, Brightwell, Ron, Gokhale, Maya, McCormick, Patrick, Ross, Robert, Shalf, John, Antypas, Katie, Donofrio, David, Dubey, Anshu, Humble, T, Schuman, C, Van Essen, Brian, Yoo, S, Aiken, A, Bernholdt, D, Cameron, Kirk, Cappello, F, Chapman, B, Chien, A, Hall, M, Hartman-Baker, R, Lan, Zhiling, Lang, M, Leidel, J, Li, S, Lucas, R, Mellor-Crummey, J, Peltz, P, Peterka, T, Strout, M, and Wilke, J
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- 2023
11. Long-term mesh-related complications from minimally invasive intraperitoneal onlay mesh for small to medium-sized ventral hernias
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Maskal, Sara M., Ellis, Ryan C., Mali, Ouen, Lau, Braden, Messer, Nir, Zheng, Xinyan, Miller, Benjamin T., Petro, Clayton C., Prabhu, Ajita S., Rosen, Michael J., and Beffa, Lucas R. A.
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- 2024
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12. Development of PVA/chitosan Nanofibers by a Green Route Using Solution Blow Spinning
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Cerqueira, Glauber R. C., Gomes, Déborah S., Victor, Rayssa S., Figueiredo, Lucas R. F., Medeiros, Eliton S., Neves, Gelmires A., Menezes, Romualdo R., and Silva, Suédina M. L.
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- 2024
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13. Disentangling contributions to past and future trends in US surface soil moisture
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Vargas Zeppetello, Lucas R., Trevino, Aleyda M., and Huybers, Peter
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- 2024
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14. Generic spectrum of the weighted Laplacian operator on Cayley graphs
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Coletti, Cristian F., de Lima, Lucas R., de Oliveira, Diego S., and Marrocos, Marcus A. M.
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- 2024
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15. Revealing the atomic and electronic mechanism of human manganese superoxide dismutase product inhibition
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Jahaun Azadmanesh, Katelyn Slobodnik, Lucas R. Struble, William E. Lutz, Leighton Coates, Kevin L. Weiss, Dean A. A. Myles, Thomas Kroll, and Gloria E. O. Borgstahl
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Science - Abstract
Abstract Human manganese superoxide dismutase (MnSOD) is a crucial oxidoreductase that maintains the vitality of mitochondria by converting superoxide (O2 ●−) to molecular oxygen (O2) and hydrogen peroxide (H2O2) with proton-coupled electron transfers (PCETs). Human MnSOD has evolved to be highly product inhibited to limit the formation of H2O2, a freely diffusible oxidant and signaling molecule. The product-inhibited complex is thought to be composed of a peroxide (O2 2−) or hydroperoxide (HO2 −) species bound to Mn ion and formed from an unknown PCET mechanism. PCET mechanisms of proteins are typically not known due to difficulties in detecting the protonation states of specific residues that coincide with the electronic state of the redox center. To shed light on the mechanism, we combine neutron diffraction and X-ray absorption spectroscopy of the product-bound, trivalent, and divalent states of the enzyme to reveal the positions of all the atoms, including hydrogen, and the electronic configuration of the metal ion. The data identifies the product-inhibited complex, and a PCET mechanism of inhibition is constructed.
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- 2024
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16. Vas deferens to rete testis anastomosis for obstructive azoospermia
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Francesco C. Mesquita, Lucas R. Campos, Luis Felipe Savio, David Miller, Jason Codrington, Joshua Theodore White, David Velasquez, Akhil Muthigi, and Ranjith Ramasamy
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Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
ABSTRACT Purpose: This video aims to present an in-depth, step-by-step tutorial on microsurgical reconstruction for obstructive azoospermia, featuring a distinctive case involving anastomosis from vas deferens to rete testis. The primary aim of this endeavor is to offer thorough and practical insights for healthcare professionals and researchers within the realm of reproductive medicine. The video endeavors to disseminate expertise, methodologies, and perspectives that can be advantageous to individuals grappling with obstructive azoospermia, providing a significant contribution to the progress of reproductive medicine and the augmentation of existing treatment alternatives. Materials and Methods: Surgical footage was recorded using the ORBEYE 4K 3D Orbital Camera System by Olympus America, with patient consent acquired for research purposes. Additionally, a retrospective examination of patient records was undertaken to compile relevant medical histories. Results: This video furnishes an exhaustive guide to microsurgical reconstruction for obstructive azoospermia, encompassing a distinctive instance of anastomosis from vas deferens to rete testis. State-of-the-art technology, such as the ORBEYE 4K 3D Orbital Camera, heightens procedural transparency, accentuating the significance of advanced instrumentation. The ethical underpinning is emphasized by obtaining patient consent for footage utilization, and a retrospective chart review augments the repository of valuable patient data. This comprehensive approach serves as an invaluable reservoir of knowledge for medical professionals and underscores excellence in clinical and ethical healthcare research. Conclusions: Anastomosis from vas deferens to rete testis emerges as a viable surgical reconstruction alternative for obstructive azoospermia, particularly when confronted with non-dilated tubules within the epididymis.
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- 2024
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17. Turbulent particle-gas feedback exacerbates the hazard impacts of pyroclastic density currents
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Daniel H. Uhle, Gert Lube, Eric C. P. Breard, Eckart Meiburg, Josef Dufek, James Ardo, Jim R. Jones, Ermanno Brosch, Lucas R. P. Corna, and Susanna F. Jenkins
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Geology ,QE1-996.5 ,Environmental sciences ,GE1-350 - Abstract
Abstract Causing one-third of all volcanic fatalities, pyroclastic density currents create destruction far beyond our current scientific explanation. Opportunities to interrogate the mechanisms behind this hazard have long been desired, but pyroclastic density currents persistently defy internal observation. Here we show, through direct measurements of destruction-causing dynamic pressure in large-scale experiments, that pressure maxima exceed theoretical values used in hazard assessments by more than one order of magnitude. These distinct pressure excursions occur through the clustering of high-momentum particles at the peripheries of coherent turbulence structures. Particle loading modifies these eddies and generates repeated high-pressure loading impacts at the frequency of the turbulence structures. Collisions of particle clusters against stationary objects generate even higher dynamic pressures that account for up to 75% of the local flow energy. To prevent severe underestimation of damage intensities, these multiphase feedback processes must be considered in hazard models that aim to mitigate volcanic risk globally.
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- 2024
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18. The extracellular matrix of dystrophic mouse diaphragm accounts for the majority of its passive stiffness and is resistant to collagenase digestion
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Wohlgemuth, Ross P, Feitzinger, Ryan M, Henricson, Kyle E, Dinh, Daryl T, Brashear, Sarah E, and Smith, Lucas R
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Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Biological Sciences ,Engineering ,Biomedical Engineering ,Medical Physiology ,Duchenne/ Becker Muscular Dystrophy ,Bioengineering ,Rare Diseases ,Muscular Dystrophy ,Pediatric ,Musculoskeletal ,Collagenase ,Decellularization ,Fibrosis ,Skeletal Muscle Mechanics - Abstract
The healthy skeletal muscle extracellular matrix (ECM) has several functions including providing structural integrity to myofibers, enabling lateral force transmission, and contributing to overall passive mechanical properties. In diseases such as Duchenne Muscular dystrophy, there is accumulation of ECM materials, primarily collagen, which results in fibrosis. Previous studies have shown that fibrotic muscle is often stiffer than healthy muscle, in part due to the increased number and altered architecture of collagen fibers within the ECM. This would imply that the fibrotic matrix is stiffer than the healthy matrix. However, while previous studies have attempted to quantify the extracellular contribution to passive stiffness in muscle, the outcomes are dependent on the type of method used. Thus, the goals of this study were to compare the stiffness of healthy and fibrotic muscle ECM and to demonstrate the efficacy of two methods for quantifying extracellular-based stiffness in muscle, namely decellularization and collagenase digestion. These methods have been demonstrated to remove the muscle fibers or ablate collagen fiber integrity, respectively, while maintaining the contents of the extracellular matrix. Using these methods in conjunction with mechanical testing on wildtype and D2.mdx mice, we found that a majority of passive stiffness in the diaphragm is dependent on the ECM, and the D2.mdx diaphragm ECM is resistant to digestion by bacterial collagenase. We propose that this resistance is due to the increased collagen cross-links and collagen packing density in the ECM of the D2.mdx diaphragm. Taken altogether, while we did not find increased stiffness of the fibrotic ECM, we did observe that the D2.mdx diaphragm conveyed resistance against collagenase digestion. These findings demonstrate how different methods for measuring ECM-based stiffness each have their own limitations and can produce different results.
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- 2023
19. The set partitioning problem in a quantum context
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Cacao, Rafael, Cortez, Lucas R. C. T., Forner, Jackson, Validi, Hamidreza, Farias, Ismael R. de, and Hicks, Illya V.
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- 2024
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20. The male imago of Fittkaulus cururuensis Savage 1986 (Leptophlebiidae: Ephemeroptera)
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Lima, Lucas R. C., Boldrini, Bianca M. P. Ottoni, and Boldrini, Rafael
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- 2023
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21. Apparent surface conductance sensitivity to vapour pressure deficit in the absence of plants
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Vargas Zeppetello, Lucas R., McColl, Kaighin A., Bernau, Jeremiah A., Bowen, Brenda B., Tang, Lois I., Holbrook, N. Michele, Gentine, Pierre, and Huybers, Peter
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- 2023
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22. Electric polarization near vortices in the extended Kitaev model
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Lucas R. D. Freitas, Tim Bauer, Reinhold Egger, and Rodrigo G. Pereira
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Materials of engineering and construction. Mechanics of materials ,TA401-492 ,Atomic physics. Constitution and properties of matter ,QC170-197 - Abstract
Abstract We formulate a Majorana mean-field theory for the extended J KΓ Kitaev model in a magnetic Zeeman field of arbitrary direction, and apply it for studying spatially inhomogeneous states harboring vortices. This mean-field theory is exact in the pure Kitaev limit and captures the essential physics throughout the Kitaev spin liquid phase. We determine the charge profile around vortices and the corresponding quadrupole tensor. The quadrupole-quadrupole interaction between distant vortices is shown to be either repulsive or attractive, depending on parameters. We predict that electrically biased scanning probe tips enable the creation of vortices at preselected positions. Our results paves the way for the electric manipulation of Ising anyons in Kitaev spin liquids.
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- 2024
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23. Database of immature stage traits of Ephemeroptera, Plecoptera, and Trichoptera (EPT) genera for the Amazon
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Santos, Natália Beatriz Barros, Cruz, Gabriel Martins, Monteles, Josinete Sampaio, de Faria, Ana Paula Justino, Firmino, Viviane Caetano, Shimano, Yulie, Ferreira, Victor Rennan Santos, Luiza-Andrade, Ana, Salles, Frederico Falcão, Castro, Diego M. P., Quinteiro, Fábio B., Lima, Lucas R. C., Dias, Lucimar G., Pes, Ana Maria O., Hamada, Neusa, and Juen, Leandro
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- 2024
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24. A genomic timescale for placental mammal evolution
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Foley, Nicole M, Mason, Victor C, Harris, Andrew J, Bredemeyer, Kevin R, Damas, Joana, Lewin, Harris A, Eizirik, Eduardo, Gatesy, John, Karlsson, Elinor K, Lindblad-Toh, Kerstin, Springer, Mark S, Murphy, William J, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Birren, Bruce W, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Di Palma, Federica, Diekhans, Mark, Dong, Michael X, Fan, Kaili, Fanter, Cornelia, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gazal, Steven, Genereux, Diane P, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Johnson, Jeremy, Juan, David, Kaplow, Irene M, Keough, Kathleen C, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Li, Xue, Lind, Abigail, Mackay-Smith, Ava, Marinescu, Voichita D, Marques-Bonet, Tomas, Meadows, Jennifer RS, Meyer, Wynn K, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pfenning, Andreas R, Phan, BaDoi N, Pollard, Katherine S, Pratt, Henry E, Ray, David A, Reilly, Steven K, Rosen, Jeb R, Ruf, Irina, Ryan, Louise, Ryder, Oliver A, Sabeti, Pardis C, Schäffer, Daniel E, Serres, Aitor, Shapiro, Beth, Smit, Arian FA, Springer, Mark, Srinivasan, Chaitanya, Steiner, Cynthia, Storer, Jessica M, Sullivan, Kevin AM, Sullivan, Patrick F, and Sundström, Elisabeth
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Genetics ,Human Genome ,Biotechnology ,Animals ,Female ,Biological Evolution ,Eutheria ,Evolution ,Molecular ,Fossils ,Genomics ,Phylogeny ,Genetic Variation ,Time Factors ,Zoonomia Consortium‡ ,General Science & Technology - Abstract
The precise pattern and timing of speciation events that gave rise to all living placental mammals remain controversial. We provide a comprehensive phylogenetic analysis of genetic variation across an alignment of 241 placental mammal genome assemblies, addressing prior concerns regarding limited genomic sampling across species. We compared neutral genome-wide phylogenomic signals using concatenation and coalescent-based approaches, interrogated phylogenetic variation across chromosomes, and analyzed extensive catalogs of structural variants. Interordinal relationships exhibit relatively low rates of phylogenomic conflict across diverse datasets and analytical methods. Conversely, X-chromosome versus autosome conflicts characterize multiple independent clades that radiated during the Cenozoic. Genomic time trees reveal an accumulation of cladogenic events before and immediately after the Cretaceous-Paleogene (K-Pg) boundary, implying important roles for Cretaceous continental vicariance and the K-Pg extinction in the placental radiation.
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- 2023
25. Comparative genomics of Balto, a famous historic dog, captures lost diversity of 1920s sled dogs
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Moon, Katherine L, Huson, Heather J, Morrill, Kathleen, Wang, Ming-Shan, Li, Xue, Srikanth, Krishnamoorthy, Lindblad-Toh, Kerstin, Svenson, Gavin J, Karlsson, Elinor K, Shapiro, Beth, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Birren, Bruce W, Bredemeyer, Kevin R, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Dong, Michael X, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gatesy, John, Gazal, Steven, Genereux, Diane P, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Johnson, Jeremy, Juan, David, Kaplow, Irene M, Keough, Kathleen C, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Lewin, Harris A, Lind, Abigail, Mackay-Smith, Ava, Marinescu, Voichita D, Marques-Bonet, Tomas, Mason, Victor C, Meadows, Jennifer RS, Meyer, Wynn K, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pfenning, Andreas R, Phan, BaDoi N, Pollard, Katherine S, Pratt, Henry E, Ray, David A, Reilly, Steven K, Rosen, Jeb R, Ruf, Irina, Ryan, Louise, Ryder, Oliver A, Sabeti, Pardis C, Schäffer, Daniel E, Serres, Aitor, Smit, Arian FA, Springer, Mark, Srinivasan, Chaitanya, Steiner, Cynthia, Storer, Jessica M, Sullivan, Kevin AM, Sullivan, Patrick F, Sundström, Elisabeth, Supple, Megan A, and Swofford, Ross
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Agricultural ,Veterinary and Food Sciences ,Biological Sciences ,Genetics ,Animals ,Dogs ,Male ,Genome ,Genomics ,Genotype ,Phenotype ,Wolves ,Biodiversity ,Genetic Variation ,Zoonomia Consortium ,General Science & Technology - Abstract
We reconstruct the phenotype of Balto, the heroic sled dog renowned for transporting diphtheria antitoxin to Nome, Alaska, in 1925, using evolutionary constraint estimates from the Zoonomia alignment of 240 mammals and 682 genomes from dogs and wolves of the 21st century. Balto shares just part of his diverse ancestry with the eponymous Siberian husky breed. Balto's genotype predicts a combination of coat features atypical for modern sled dog breeds, and a slightly smaller stature. He had enhanced starch digestion compared with Greenland sled dogs and a compendium of derived homozygous coding variants at constrained positions in genes connected to bone and skin development. We propose that Balto's population of origin, which was less inbred and genetically healthier than that of modern breeds, was adapted to the extreme environment of 1920s Alaska.
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- 2023
26. The contribution of historical processes to contemporary extinction risk in placental mammals
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Wilder, Aryn P, Supple, Megan A, Subramanian, Ayshwarya, Mudide, Anish, Swofford, Ross, Serres-Armero, Aitor, Steiner, Cynthia, Koepfli, Klaus-Peter, Genereux, Diane P, Karlsson, Elinor K, Lindblad-Toh, Kerstin, Marques-Bonet, Tomas, Munoz Fuentes, Violeta, Foley, Kathleen, Meyer, Wynn K, Ryder, Oliver A, Shapiro, Beth, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Birren, Bruce W, Bredemeyer, Kevin R, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Dong, Michael X, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gatesy, John, Gazal, Steven, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Johnson, Jeremy, Juan, David, Kaplow, Irene M, Keough, Kathleen C, Kirilenko, Bogdan, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Lewin, Harris A, Li, Xue, Lind, Abigail, Mackay-Smith, Ava, Marinescu, Voichita D, Mason, Victor C, Meadows, Jennifer RS, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pfenning, Andreas R, Phan, BaDoi N, Pollard, Katherine S, Pratt, Henry E, Ray, David A, Reilly, Steven K, Rosen, Jeb R, Ruf, Irina, Ryan, Louise, Sabeti, Pardis C, Schäffer, Daniel E, Serres, Aitor, Smit, Arian FA, Springer, Mark, and Srinivasan, Chaitanya
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Biological Sciences ,Evolutionary Biology ,Genetics ,Behavioral and Social Science ,Human Genome ,Basic Behavioral and Social Science ,Life on Land ,Animals ,Female ,Pregnancy ,Eutheria ,Extinction ,Biological ,Genetic Variation ,Genome ,Population Density ,Risk ,Zoonomia Consortium‡ ,General Science & Technology - Abstract
Species persistence can be influenced by the amount, type, and distribution of diversity across the genome, suggesting a potential relationship between historical demography and resilience. In this study, we surveyed genetic variation across single genomes of 240 mammals that compose the Zoonomia alignment to evaluate how historical effective population size (Ne) affects heterozygosity and deleterious genetic load and how these factors may contribute to extinction risk. We find that species with smaller historical Ne carry a proportionally larger burden of deleterious alleles owing to long-term accumulation and fixation of genetic load and have a higher risk of extinction. This suggests that historical demography can inform contemporary resilience. Models that included genomic data were predictive of species' conservation status, suggesting that, in the absence of adequate census or ecological data, genomic information may provide an initial risk assessment.
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- 2023
27. The functional and evolutionary impacts of human-specific deletions in conserved elements
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Xue, James R, Mackay-Smith, Ava, Mouri, Kousuke, Garcia, Meilin Fernandez, Dong, Michael X, Akers, Jared F, Noble, Mark, Li, Xue, Lindblad-Toh, Kerstin, Karlsson, Elinor K, Noonan, James P, Capellini, Terence D, Brennand, Kristen J, Tewhey, Ryan, Sabeti, Pardis C, Reilly, Steven K, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Birren, Bruce W, Bredemeyer, Kevin R, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gatesy, John, Gazal, Steven, Genereux, Diane P, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Johnson, Jeremy, Juan, David, Kaplow, Irene M, Keough, Kathleen C, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Lewin, Harris A, Lind, Abigail, Marinescu, Voichita D, Marques-Bonet, Tomas, Mason, Victor C, Meadows, Jennifer RS, Meyer, Wynn K, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pfenning, Andreas R, Phan, BaDoi N, Pollard, Katherine S, Pratt, Henry E, Ray, David A, Rosen, Jeb R, Ruf, Irina, Ryan, Louise, Ryder, Oliver A, Schäffer, Daniel E, Serres, Aitor, Shapiro, Beth, Smit, Arian FA, Springer, Mark, Srinivasan, Chaitanya, and Steiner, Cynthia
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Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Biotechnology ,Neurosciences ,Human Genome ,1.1 Normal biological development and functioning ,Underpinning research ,Generic health relevance ,Neurological ,Humans ,Conserved Sequence ,Evolution ,Molecular ,Genome ,Genomics ,RNA-Binding Proteins ,Sequence Deletion ,Brain ,Gene Expression Regulation ,Developmental ,Zoonomia Consortium† ,General Science & Technology - Abstract
Conserved genomic sequences disrupted in humans may underlie uniquely human phenotypic traits. We identified and characterized 10,032 human-specific conserved deletions (hCONDELs). These short (average 2.56 base pairs) deletions are enriched for human brain functions across genetic, epigenomic, and transcriptomic datasets. Using massively parallel reporter assays in six cell types, we discovered 800 hCONDELs conferring significant differences in regulatory activity, half of which enhance rather than disrupt regulatory function. We highlight several hCONDELs with putative human-specific effects on brain development, including HDAC5, CPEB4, and PPP2CA. Reverting an hCONDEL to the ancestral sequence alters the expression of LOXL2 and developmental genes involved in myelination and synaptic function. Our data provide a rich resource to investigate the evolutionary mechanisms driving new traits in humans and other species.
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- 2023
28. Integrating gene annotation with orthology inference at scale
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Kirilenko, Bogdan M, Munegowda, Chetan, Osipova, Ekaterina, Jebb, David, Sharma, Virag, Blumer, Moritz, Morales, Ariadna E, Ahmed, Alexis-Walid, Kontopoulos, Dimitrios-Georgios, Hilgers, Leon, Lindblad-Toh, Kerstin, Karlsson, Elinor K, Hiller, Michael, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Birren, Bruce W, Bredemeyer, Kevin R, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Dong, Michael X, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gatesy, John, Gazal, Steven, Genereux, Diane P, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Johnson, Jeremy, Juan, David, Kaplow, Irene M, Keough, Kathleen C, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Lewin, Harris A, Li, Xue, Lind, Abigail, Mackay-Smith, Ava, Marinescu, Voichita D, Marques-Bonet, Tomas, Mason, Victor C, Meadows, Jennifer RS, Meyer, Wynn K, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pfenning, Andreas R, Phan, BaDoi N, Pollard, Katherine S, Pratt, Henry E, Ray, David A, Reilly, Steven K, Rosen, Jeb R, Ruf, Irina, Ryan, Louise, Ryder, Oliver A, Sabeti, Pardis C, Schäffer, Daniel E, Serres, Aitor, Shapiro, Beth, Smit, Arian FA, Springer, Mark, Srinivasan, Chaitanya, Steiner, Cynthia, Storer, Jessica M, Sullivan, Kevin AM, and Sullivan, Patrick F
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Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Biotechnology ,Human Genome ,Generic health relevance ,Animals ,Female ,Mice ,Eutheria ,Genome ,Genomics ,Molecular Sequence Annotation ,Birds ,Zoonomia Consortium‡ ,General Science & Technology - Abstract
Annotating coding genes and inferring orthologs are two classical challenges in genomics and evolutionary biology that have traditionally been approached separately, limiting scalability. We present TOGA (Tool to infer Orthologs from Genome Alignments), a method that integrates structural gene annotation and orthology inference. TOGA implements a different paradigm to infer orthologous loci, improves ortholog detection and annotation of conserved genes compared with state-of-the-art methods, and handles even highly fragmented assemblies. TOGA scales to hundreds of genomes, which we demonstrate by applying it to 488 placental mammal and 501 bird assemblies, creating the largest comparative gene resources so far. Additionally, TOGA detects gene losses, enables selection screens, and automatically provides a superior measure of mammalian genome quality. TOGA is a powerful and scalable method to annotate and compare genes in the genomic era.
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- 2023
29. Relating enhancer genetic variation across mammals to complex phenotypes using machine learning
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Kaplow, Irene M, Lawler, Alyssa J, Schäffer, Daniel E, Srinivasan, Chaitanya, Sestili, Heather H, Wirthlin, Morgan E, Phan, BaDoi N, Prasad, Kavya, Brown, Ashley R, Zhang, Xiaomeng, Foley, Kathleen, Genereux, Diane P, Karlsson, Elinor K, Lindblad-Toh, Kerstin, Meyer, Wynn K, Pfenning, Andreas R, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Birren, Bruce W, Bredemeyer, Kevin R, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Dong, Michael X, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gatesy, John, Gazal, Steven, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Johnson, Jeremy, Juan, David, Keough, Kathleen C, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Lewin, Harris A, Li, Xue, Lind, Abigail, Mackay-Smith, Ava, Marinescu, Voichita D, Marques-Bonet, Tomas, Mason, Victor C, Meadows, Jennifer RS, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pollard, Katherine S, Pratt, Henry E, Ray, David A, Reilly, Steven K, Rosen, Jeb R, Ruf, Irina, Ryan, Louise, Ryder, Oliver A, Sabeti, Pardis C, Serres, Aitor, Shapiro, Beth, Smit, Arian FA, Springer, Mark, and Steiner, Cynthia
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Biological Sciences ,Genetics ,Pediatric ,Human Genome ,Rare Diseases ,Congenital Structural Anomalies ,Underpinning research ,1.1 Normal biological development and functioning ,Neurological ,Mental health ,Animals ,Enhancer Elements ,Genetic ,Genetic Variation ,Machine Learning ,Mammals ,Phenotype ,Zoonomia Consortium** ,General Science & Technology - Abstract
Protein-coding differences between species often fail to explain phenotypic diversity, suggesting the involvement of genomic elements that regulate gene expression such as enhancers. Identifying associations between enhancers and phenotypes is challenging because enhancer activity can be tissue-dependent and functionally conserved despite low sequence conservation. We developed the Tissue-Aware Conservation Inference Toolkit (TACIT) to associate candidate enhancers with species' phenotypes using predictions from machine learning models trained on specific tissues. Applying TACIT to associate motor cortex and parvalbumin-positive interneuron enhancers with neurological phenotypes revealed dozens of enhancer-phenotype associations, including brain size-associated enhancers that interact with genes implicated in microcephaly or macrocephaly. TACIT provides a foundation for identifying enhancers associated with the evolution of any convergently evolved phenotype in any large group of species with aligned genomes.
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- 2023
30. Three-dimensional genome rewiring in loci with human accelerated regions
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Keough, Kathleen C, Whalen, Sean, Inoue, Fumitaka, Przytycki, Pawel F, Fair, Tyler, Deng, Chengyu, Steyert, Marilyn, Ryu, Hane, Lindblad-Toh, Kerstin, Karlsson, Elinor, Nowakowski, Tomasz, Ahituv, Nadav, Pollen, Alex, Pollard, Katherine S, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Birren, Bruce W, Bredemeyer, Kevin R, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Dong, Michael X, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gatesy, John, Gazal, Steven, Genereux, Diane P, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Johnson, Jeremy, Juan, David, Kaplow, Irene M, Karlsson, Elinor K, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Lewin, Harris A, Li, Xue, Lind, Abigail, Mackay-Smith, Ava, Marinescu, Voichita D, Marques-Bonet, Tomas, Mason, Victor C, Meadows, Jennifer RS, Meyer, Wynn K, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pfenning, Andreas R, Phan, BaDoi N, Pratt, Henry E, Ray, David A, Reilly, Steven K, Rosen, Jeb R, Ruf, Irina, Ryan, Louise, Ryder, Oliver A, Sabeti, Pardis C, Schäffer, Daniel E, Serres, Aitor, Shapiro, Beth, Smit, Arian FA, Springer, Mark, Srinivasan, Chaitanya, Steiner, Cynthia, Storer, Jessica M, and Sullivan, Kevin AM
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Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Stem Cell Research ,Human Genome ,Biotechnology ,Underpinning research ,1.1 Normal biological development and functioning ,Animals ,Humans ,Chromatin ,Genome ,Human ,Genomics ,Pan troglodytes ,Genetic Loci ,Neurogenesis ,Deep Learning ,Zoonomia Consortium§ ,General Science & Technology - Abstract
Human accelerated regions (HARs) are conserved genomic loci that evolved at an accelerated rate in the human lineage and may underlie human-specific traits. We generated HARs and chimpanzee accelerated regions with an automated pipeline and an alignment of 241 mammalian genomes. Combining deep learning with chromatin capture experiments in human and chimpanzee neural progenitor cells, we discovered a significant enrichment of HARs in topologically associating domains containing human-specific genomic variants that change three-dimensional (3D) genome organization. Differential gene expression between humans and chimpanzees at these loci suggests rewiring of regulatory interactions between HARs and neurodevelopmental genes. Thus, comparative genomics together with models of 3D genome folding revealed enhancer hijacking as an explanation for the rapid evolution of HARs.
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- 2023
31. Evolutionary constraint and innovation across hundreds of placental mammals
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Christmas, Matthew J, Kaplow, Irene M, Genereux, Diane P, Dong, Michael X, Hughes, Graham M, Li, Xue, Sullivan, Patrick F, Hindle, Allyson G, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Breit, Ana M, Diekhans, Mark, Fanter, Cornelia, Foley, Nicole M, Goodman, Daniel B, Goodman, Linda, Keough, Kathleen C, Kirilenko, Bogdan, Kowalczyk, Amanda, Lawless, Colleen, Lind, Abigail L, Meadows, Jennifer RS, Moreira, Lucas R, Redlich, Ruby W, Ryan, Louise, Swofford, Ross, Valenzuela, Alejandro, Wagner, Franziska, Wallerman, Ola, Brown, Ashley R, Damas, Joana, Fan, Kaili, Gatesy, John, Grimshaw, Jenna, Johnson, Jeremy, Kozyrev, Sergey V, Lawler, Alyssa J, Marinescu, Voichita D, Morrill, Kathleen M, Osmanski, Austin, Paulat, Nicole S, Phan, BaDoi N, Reilly, Steven K, Schäffer, Daniel E, Steiner, Cynthia, Supple, Megan A, Wilder, Aryn P, Wirthlin, Morgan E, Xue, James R, Birren, Bruce W, Gazal, Steven, Hubley, Robert M, Koepfli, Klaus-Peter, Marques-Bonet, Tomas, Meyer, Wynn K, Nweeia, Martin, Sabeti, Pardis C, Shapiro, Beth, Smit, Arian FA, Springer, Mark S, Teeling, Emma C, Weng, Zhiping, Hiller, Michael, Levesque, Danielle L, Lewin, Harris A, Murphy, William J, Navarro, Arcadi, Paten, Benedict, Pollard, Katherine S, Ray, David A, Ruf, Irina, Ryder, Oliver A, Pfenning, Andreas R, Lindblad-Toh, Kerstin, Karlsson, Elinor K, Bredemeyer, Kevin R, Clawson, Hiram, Di Palma, Federica, Eizirik, Eduardo, Forsberg-Nilsson, Karin, Garcia, Carlos J, and Halsey, Michaela K
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Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Biotechnology ,Human Genome ,Animals ,Female ,Humans ,Conserved Sequence ,Eutheria ,Evolution ,Molecular ,Genome ,Human ,Zoonomia Consortium§ ,General Science & Technology - Abstract
Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (~10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.
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- 2023
32. Leveraging base-pair mammalian constraint to understand genetic variation and human disease
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Sullivan, Patrick F, Meadows, Jennifer RS, Gazal, Steven, Phan, BaDoi N, Li, Xue, Genereux, Diane P, Dong, Michael X, Bianchi, Matteo, Andrews, Gregory, Sakthikumar, Sharadha, Nordin, Jessika, Roy, Ananya, Christmas, Matthew J, Marinescu, Voichita D, Wang, Chao, Wallerman, Ola, Xue, James, Yao, Shuyang, Sun, Quan, Szatkiewicz, Jin, Wen, Jia, Huckins, Laura M, Lawler, Alyssa, Keough, Kathleen C, Zheng, Zhili, Zeng, Jian, Wray, Naomi R, Li, Yun, Johnson, Jessica, Chen, Jiawen, Paten, Benedict, Reilly, Steven K, Hughes, Graham M, Weng, Zhiping, Pollard, Katherine S, Pfenning, Andreas R, Forsberg-Nilsson, Karin, Karlsson, Elinor K, Lindblad-Toh, Kerstin, Armstrong, Joel C, Birren, Bruce W, Bredemeyer, Kevin R, Breit, Ana M, Clawson, Hiram, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Garcia, Carlos J, Gatesy, John, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Johnson, Jeremy, Juan, David, Kaplow, Irene M, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Lewin, Harris A, Lind, Abigail, Mackay-Smith, Ava, Marques-Bonet, Tomas, Mason, Victor C, Meyer, Wynn K, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, and Navarro, Arcadi
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Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Biotechnology ,Clinical Research ,Human Genome ,Brain Disorders ,Generic health relevance ,Animals ,Humans ,Biological Evolution ,Genetic Variation ,Genome ,Human ,Genome-Wide Association Study ,Genomics ,Molecular Sequence Annotation ,Polymorphism ,Single Nucleotide ,Disease ,Zoonomia Consortium§ ,General Science & Technology - Abstract
Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function, agnostic to cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% of the human genome as significantly constrained and likely functional. We compared phyloP scores to genome annotation, association studies, copy-number variation, clinical genetics findings, and cancer data. Constrained positions are enriched for variants that explain common disease heritability more than other functional annotations. Our results improve variant annotation but also highlight that the regulatory landscape of the human genome still needs to be further explored and linked to disease.
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- 2023
33. Chronic Kidney Disease is Associated With Attenuated Plasma Metabolome Response to Oral Glucose Tolerance Testing
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Ahmadi, Armin, Huda, M Nazmul, Bennett, Brian J, Gamboa, Jorge, Zelnick, Leila R, Smith, Lucas R, Chondronikola, Maria, Raftery, Daniel, de Boer, Ian H, and Roshanravan, Baback
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Medical Biochemistry and Metabolomics ,Biomedical and Clinical Sciences ,Kidney Disease ,Nutrition ,Clinical Research ,Metabolic and endocrine ,Renal and urogenital ,Humans ,Glucose Tolerance Test ,Insulin Resistance ,Renal Insufficiency ,Chronic ,Insulin ,Glucose ,Metabolome ,Blood Glucose ,Chronic kidney disease ,metabolism ,insulin resistance ,insulin resistance. ,Clinical Sciences ,Nutrition and Dietetics ,Urology & Nephrology ,Clinical sciences ,Nutrition and dietetics - Abstract
ObjectiveChronic kidney disease (CKD) is associated with decreased anabolic response to insulin contributing to protein-energy wasting. Targeted metabolic profiling of oral glucose tolerance testing (OGTT) may help identify metabolic pathways contributing to disruptions to insulin response in CKD.MethodsUsing targeted metabolic profiling, we studied the plasma metabolome response in 41 moderate-to-severe nondiabetic CKD patients and 20 healthy controls at fasting and 2 hours after an oral glucose load. We used linear mixed modeling with random intercepts, adjusting for age, gender, race/ethnicity, body weight, and batch to assess heterogeneity in response to OGTT by CKD status.ResultsMean estimated glomerular filtration rate among CKD participants was 38.9 ± 12.7 mL/min per 1.73 m2 compared to 87.2 ± 17.7 mL/min per 1.73 m2 among controls. Glucose ingestion induced an anabolic response resulting in increased glycolysis products and a reduction in a wide range of metabolites including amino acids, tricarboxylic acid cycle intermediates, and purine nucleotides compared to fasting. Participants with CKD demonstrated a blunted anabolic response to OGTT evidenced by significant changes in 13 metabolites compared to controls. The attenuated metabolome response predominant involved mitochondrial energy metabolism, vitamin B family, and purine nucleotides. Compared to controls, CKD participants had elevated lactate:pyruvate (L:P) ratio and decreased guanosine diphosphate:guanosine triphosphate ratio during OGTT.ConclusionMetabolic profiling of OGTT response suggests a broad disruption of mitochondrial energy metabolism in CKD patients. These findings motivate further investigation into the impact of insulin sensitizers and mitochondrial targeted therapeutics on energy metabolism in patients with nondiabetic CKD.
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- 2023
34. First report and injury of Delia sanctijacobi (Bigot, 1885) (Diptera: Anthomyiidae) on tomato crop in Brazil
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Rodolfo V. Castilhos, Juracy C. Lins Junior, Janaína P. Santos, and Lucas R. P. Gomes
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root maggot fly ,Solanum lycopersicum L. ,emerging pest ,Zoology ,QL1-991 - Abstract
The root maggot fly, Delia sanctijacobi (Bigot, 1885) (Diptera: Anthomyiidae), is an emerging pest of many vegetables. In this note, we report for the first time the occurrence of D. sanctijacobi damaging the tomato (Solanum lycopersicum L.) culture in Brazil. The occurrence was recorded in a tomato field located in the municipality of Coronel Freitas, Santa Catarina. The damage was characterized by roots consumption, opening of galleries in the stem and plant stand reduction. The first detection of D. sanctijacobi on tomato in Brazil brings an alert to growers and the need of future research about population dynamics and development of management strategies for this species.
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- 2024
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35. The set partitioning problem in a quantum context.
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Rafael Cação, Lucas R. C. T. Cortez, Jackson Forner, Hamidreza Validi, Ismael R. de Farias Jr., and Illya V. Hicks
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- 2024
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36. Engineered multi-functional, pro-angiogenic collagen-based scaffolds loaded with endothelial cells promote large deep burn wound healing
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Song, Hengyue, Gao, Kewa, Hao, Dake, Li, Andrew, Liu, Ruiwu, Anggito, Bryan, Yin, Boyan, Jin, Qianyu, Dartora, Vanessa, Lam, Kit S, Smith, Lucas R, Panitch, Alyssa, Zhou, Jianda, Farmer, Diana L, and Wang, Aijun
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Wound Healing and Care ,Physical Injury - Accidents and Adverse Effects ,deep burn wound ,endothelial cell ,wound healing ,vascularization ,ECM scaffold ,Pharmacology and pharmaceutical sciences - Abstract
The lack of vascularization associated with deep burns delays the construction of wound beds, increases the risks of infection, and leads to the formation of hypertrophic scars or disfigurement. To address this challenge, we have fabricated a multi-functional pro-angiogenic molecule by grafting integrin αvβ3 ligand LXW7 and collagen-binding peptide (SILY) to a dermatan sulfate (DS) glycosaminoglycan backbone, named LXW7-DS-SILY (LDS), and further employed this to functionalize collagen-based Integra scaffolds. Using a large deep burn wound model in C57/BLK6 mice (8-10 weeks old, 26-32g, n = 39), we demonstrated that LDS-modified collagen-based Integra scaffolds loaded with endothelial cells (ECs) accelerate wound healing rate, re-epithelialization, vascularization, and collagen deposition. Specifically, a 2 cm × 3 cm full-thickness skin burn wound was created 48 h after the burn, and then wounds were treated with four groups of different dressing scaffolds, including Integra + ECs, Integra + LDS, and Integra + LDS + ECs with Integra-only as the control. Digital photos were taken for wound healing measurement on post-treatment days 1, 7, 14, 21, 28, and 35. Post-treatment photos revealed that treatment with the Intgera + LDS + ECs scaffold exhibited a higher wound healing rate in the proliferation phase. Histology results showed significantly increased re-epithelialization, increased collagen deposition, increased thin and mixed collagen fiber content, increased angiogenesis, and shorter wound length within the Integra + LDS + ECs group at Day 35. On Day 14, the Integra + LDS + ECs group showed the same trend. The relative proportions of collagen changed from Day 14 to Day 35 in the Integra + LDS + ECs and Integra + ECs groups demonstrated decreased thick collagen fiber deposition and greater thin and mixed collagen fiber deposition. LDS-modified Integra scaffolds represent a promising novel treatment to accelerate deep burn wound healing, thereby potentially reducing the morbidity associated with open burn wounds. These scaffolds can also potentially reduce the need for autografting and morbidity in patients with already limited areas of harvestable skin.
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- 2023
37. StrainGE: a toolkit to track and characterize low-abundance strains in complex microbial communities
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van Dijk, Lucas R, Walker, Bruce J, Straub, Timothy J, Worby, Colin J, Grote, Alexandra, Schreiber, Henry L, Anyansi, Christine, Pickering, Amy J, Hultgren, Scott J, Manson, Abigail L, Abeel, Thomas, and Earl, Ashlee M
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Human Genome ,Genetics ,Infection ,Bacteria ,Humans ,Metagenome ,Metagenomics ,Microbiota ,Microbiome ,Strain-tracking ,Environmental Sciences ,Biological Sciences ,Information and Computing Sciences ,Bioinformatics - Abstract
Human-associated microbial communities comprise not only complex mixtures of bacterial species, but also mixtures of conspecific strains, the implications of which are mostly unknown since strain level dynamics are underexplored due to the difficulties of studying them. We introduce the Strain Genome Explorer (StrainGE) toolkit, which deconvolves strain mixtures and characterizes component strains at the nucleotide level from short-read metagenomic sequencing with higher sensitivity and resolution than other tools. StrainGE is able to identify strains at 0.1x coverage and detect variants for multiple conspecific strains within a sample from coverages as low as 0.5x.
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- 2022
38. Downregulation of Microcephaly-Causing Genes as a Mechanism for ZIKV Teratogenesis: A Meta-analysis of RNA-Seq Studies
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Gomes, Julia A., Sgarioni, Eduarda, Kowalski, Thayne W., Giudicelli, Giovanna C., Recamonde-Mendoza, Mariana, Fraga, Lucas R., Schüler-Faccini, Lavínia, and Vianna, Fernanda S. L.
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- 2023
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39. Drivers and timing of grass carp movement within the Sandusky River, Ohio: implications to potential spawning barrier response strategy
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Bopp, Justin J., Brenden, Travis O., Faust, Matthew D., Vandergoot, Christopher S., Kraus, Richard T., Roberts, James J., and Nathan, Lucas R.
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- 2023
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40. Effect of the Support (Silica vs Niobia) and the Pressure (Atmospheric vs High Pressure) on the Catalytic Performance of Pd Based Catalysts for the Hydrodeoxygenation of m-Cresol
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Teles, Camila A., Francisco, Lucas R., Gonçalves, Vinicius O. O., Noronha, Fábio B., and Richard, Frédéric
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- 2023
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41. An environmental justice analysis of air pollution emissions in the United States from 1970 to 2010
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Yanelli Nunez, Jaime Benavides, Jenni A. Shearston, Elena M. Krieger, Misbath Daouda, Lucas R. F. Henneman, Erin E. McDuffie, Jeff Goldsmith, Joan A. Casey, and Marianthi-Anna Kioumourtzoglou
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Science - Abstract
Abstract Over the last decades, air pollution emissions have decreased substantially; however, inequities in air pollution persist. We evaluate county-level racial/ethnic and socioeconomic disparities in emissions changes from six air pollution source sectors (industry [SO2], energy [SO2, NOx], agriculture [NH3], commercial [NOx], residential [particulate organic carbon], and on-road transportation [NOx]) in the contiguous United States during the 40 years following the Clean Air Act (CAA) enactment (1970-2010). We calculate relative emission changes and examine the differential changes given county demographics using hierarchical nested models. The results show racial/ethnic disparities, particularly in the industry and energy generation source sectors. We also find that median family income is a driver of variation in relative emissions changes in all sectors—counties with median family income >$75 K vs. less generally experience larger relative declines in industry, energy, transportation, residential, and commercial-related emissions. Emissions from most air pollution source sectors have, on a national level, decreased following the United States CAA. In this work, we show that the relative reductions in emissions varied across racial/ethnic and socioeconomic groups.
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- 2024
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42. Phytocannabinoids: Pharmacological effects, biomedical applications, and worldwide prospection
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Ana L.G. de Brito Siqueira, Pedro V.V. Cremasco, Juliana O. Bahú, Aline Pioli da Silva, Lucas R. Melo de Andrade, Paula G.A. González, Sara Crivellin, Viktor O. Cárdenas Concha, Karolline Krambeck, Leandro Lodi, Patrícia Severino, and Eliana B. Souto
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Cannabidiol ,Cannabis Sativa L. ,Commercial products ,Market ,Trans-Delta-9-tetrahydrocannabinol ,Medicine - Abstract
Scientific evidence exists about the association between neurological diseases (i.e., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, depression, and memory loss) and oxidative damage. The increasing worldwide incidence of such diseases is attracting the attention of researchers to find palliative medications to reduce the symptoms and promote quality of life, in particular, in developing countries, e.g., South America and Africa. Among potential alternatives, extracts of Cannabis Sativa L. are suitable for people who have neurological disorders, spasticity, and pain, nausea, resulting from diseases such as cancer and arthritis. In this review, we discuss the latest developments in the use of Cannabis, its subtypes and constituents, extraction methods, and relevant pharmacological effects. Biomedical applications, marketed products, and prospects for the worldwide use of Cannabis Sativa L. extracts are also discussed, providing the bibliometric maps of scientific literature published in representative countries from South America (i.e., Brazil) and Africa (i.e., South Africa). A lack of evidence on the effectiveness and safety of Cannabis, besides the concerns about addiction and other adverse events, has led many countries to act with caution before changing Cannabis-related regulations. Recent findings are expected to increase the social acceptance of Cannabis, while new technologies seem to boost the global cannabis market because the benefits of (−)-trans-delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) use have been proven in several studies in addition to the potential to general new employment.
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- 2023
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43. Evolution of the ancestral mammalian karyotype and syntenic regions
- Author
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Damas, Joana, Corbo, Marco, Kim, Jaebum, Turner-Maier, Jason, Farré, Marta, Larkin, Denis M, Ryder, Oliver A, Steiner, Cynthia, Houck, Marlys L, Hall, Shaune, Shiue, Lily, Thomas, Stephen, Swale, Thomas, Daly, Mark, Korlach, Jonas, Uliano-Silva, Marcela, Mazzoni, Camila J, Birren, Bruce W, Genereux, Diane P, Johnson, Jeremy, Lindblad-Toh, Kerstin, Karlsson, Elinor K, Nweeia, Martin T, Johnson, Rebecca N, Lewin, Harris A, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Bredemeyer, Kevin R, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Di Palma, Federica, Diekhans, Mark, Dong, Michael X, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gatesy, John, Gazal, Steven, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Juan, David, Kaplow, Irene M, Keough, Kathleen C, Kirilenko, Bogdan, Koepfli, Klaus-Peter, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Li, Xue, Lind, Abigail, Mackay-Smith, Ava, Marinescu, Voichita D, Marques-Bonet, Tomas, Mason, Victor C, Meadows, Jennifer RS, Meyer, Wynn K, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pfenning, Andreas R, Phan, BaDoi N, Pollard, Katherine S, Pratt, Henry E, Ray, David A, Reilly, Steven K, Rosen, Jeb R, Ruf, Irina, and Ryan, Louise
- Subjects
Biological Sciences ,Bioinformatics and Computational Biology ,Evolutionary Biology ,Genetics ,Human Genome ,Generic health relevance ,Animals ,Cattle ,Chromosomes ,Mammalian ,Eutheria ,Evolution ,Molecular ,Humans ,Karyotype ,Mammals ,Phylogeny ,Sloths ,Synteny ,chromosome evolution ,mammals ,synteny conservation ,ancestral genome reconstruction ,topologically associating domains ,Zoonomia Consortium - Abstract
Decrypting the rearrangements that drive mammalian chromosome evolution is critical to understanding the molecular bases of speciation, adaptation, and disease susceptibility. Using 8 scaffolded and 26 chromosome-scale genome assemblies representing 23/26 mammal orders, we computationally reconstructed ancestral karyotypes and syntenic relationships at 16 nodes along the mammalian phylogeny. Three different reference genomes (human, sloth, and cattle) representing phylogenetically distinct mammalian superorders were used to assess reference bias in the reconstructed ancestral karyotypes and to expand the number of clades with reconstructed genomes. The mammalian ancestor likely had 19 pairs of autosomes, with nine of the smallest chromosomes shared with the common ancestor of all amniotes (three still conserved in extant mammals), demonstrating a striking conservation of synteny for ∼320 My of vertebrate evolution. The numbers and types of chromosome rearrangements were classified for transitions between the ancestral mammalian karyotype, descendent ancestors, and extant species. For example, 94 inversions, 16 fissions, and 14 fusions that occurred over 53 My differentiated the therian from the descendent eutherian ancestor. The highest breakpoint rate was observed between the mammalian and therian ancestors (3.9 breakpoints/My). Reconstructed mammalian ancestor chromosomes were found to have distinct evolutionary histories reflected in their rates and types of rearrangements. The distributions of genes, repetitive elements, topologically associating domains, and actively transcribed regions in multispecies homologous synteny blocks and evolutionary breakpoint regions indicate that purifying selection acted over millions of years of vertebrate evolution to maintain syntenic relationships of developmentally important genes and regulatory landscapes of gene-dense chromosomes.
- Published
- 2022
44. Influence of quasicrystalline fillers on the microstructural, thermal, and band gap properties of polyamide 6-based coatings with pure Al–Cu–Fe and recycled Al–Cu–Fe quasicrystals
- Author
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Sousa, Antonia P., Lima, Wictor M. P. A., Torquato, Ramon A., Figueiredo, Lucas R. F., Oliveira, Danniel F., and Cavalcante, Danielle G. L.
- Published
- 2023
- Full Text
- View/download PDF
45. Regulation of mouse exploratory behaviour by irradiance and cone-opponent signals
- Author
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Tamayo, E., Mouland, J. W., Lucas, R. J., and Brown, T. M.
- Published
- 2023
- Full Text
- View/download PDF
46. Potential immunosuppressive clonal hematopoietic mutations in tumor infiltrating immune cells in breast invasive carcinoma
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Anandakrishnan, Ramu, Zyvoloski, Ian J., Zyvoloski, Lucas R., Opoku, Nana K., Dai, Andrew, and Antony, Veneeth
- Published
- 2023
- Full Text
- View/download PDF
47. Gut microbiome transitions across generations in different ethnicities in an urban setting—the HELIUS study
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van der Vossen, Eduard W. J., Davids, Mark, Bresser, Lucas R. F., Galenkamp, Henrike, van den Born, Bert-Jan H., Zwinderman, Aeilko H., Levin, Evgeni, Nieuwdorp, Max, and de Goffau, Marcus C.
- Published
- 2023
- Full Text
- View/download PDF
48. CLASSIFICATION OF THE OCCURRENCE OF BROADLEAF WEEDS IN NARROW-LEAF CROPS
- Author
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Cenneya L. Martins, Agda L. G. Oliveira, Isabella A. da Cunha, Henrique Oldoni, Juliana C. Pereira, and Lucas R. do Amaral
- Subjects
precision agriculture ,machine learning ,remote sensing ,weed management ,Agriculture (General) ,S1-972 - Abstract
ABSTRACT Considering the spectral differences between broadleaf weeds and narrow-leaf crops and the influence of terrain and soil variables on weed infestations, integrating such information into a machine-learning algorithm can lead to accurate weed maps. Therefore, we aim to evaluate the effectiveness of these variables in classifying the occurrence of broadleaf weeds in narrow-leaf crops. Weed data was collected at georeferenced points across two areas covering 200 ha (pasture) and 106 ha (sorghum), creating classes 0 (absence) and 1 (presence). For each sample point, we obtained 11 variables: soil clay content, cation exchange capacity, soil organic matter, terrain elevation, slope, NDVI, EVI, CIgreen, BGND (derived from PlanetScope images), and spatial information (X and Y coordinates). These variables were used as predictors of broadleaf weed presence and absence in the Random Forest classification algorithm. The presence and absence of broadleaf weeds were correctly classified in 84% and 74% of all predictions in the test sample sets for pasture and sorghum areas, respectively. This strategy represents an efficient way to map and manage the occurrence of broadleaf weeds in narrow-leaf crops.
- Published
- 2024
- Full Text
- View/download PDF
49. The end of the reign of a 'master regulator’’? A defect in function of the LasR quorum sensing regulator is a common feature of Pseudomonas aeruginosa isolates
- Author
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Mylène C. Trottier, Thays de Oliveira Pereira, Marie-Christine Groleau, Lucas R. Hoffman, Ajai A. Dandekar, and Eric Déziel
- Subjects
quorum sensing ,Pseudomonas aeruginosa ,virulence regulation ,ecology ,adaptive mutations ,opportunistic infections ,Microbiology ,QR1-502 - Abstract
ABSTRACTPseudomonas aeruginosa, a bacterium causing infections in immunocompromised individuals, regulates several of its virulence functions using three interlinked quorum sensing (QS) systems (las, rhl, and pqs). Despite its presumed importance in regulating virulence, dysfunction of the las system regulator LasR occurs frequently in strains isolated from various environments, including clinical infections. This newfound abundance of LasR-defective strains calls into question existing hypotheses regarding their selection. Indeed, current assumptions concerning factors driving the emergence of LasR-deficient isolates and the role of LasR in the QS hierarchy must be reconsidered. Here, we propose that LasR is not the primary master regulator of QS in all P. aeruginosa genetic backgrounds, even though it remains ecologically significant. We also revisit and complement current knowledge on the ecology of LasR-dependent QS in P. aeruginosa, discuss the hypotheses explaining the putative adaptive benefits of selecting against LasR function, and consider the implications of this renewed understanding.
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- 2024
- Full Text
- View/download PDF
50. Walking training with auditory cueing improves walking speed more than walking training alone in ambulatory people with Parkinson’s disease: a systematic review
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Nascimento, Lucas R, Boening, Augusto, Rocha, Rafaela JS, do Carmo, Willian A, and Ada, Louise
- Published
- 2024
- Full Text
- View/download PDF
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