{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe collection of abstracts primarily details the multifaceted roles of members of the TGF‐β superfamily—especially the Lefty proteins—in regulating key developmental processes. Several studies demonstrate that Lefty is central to establishing embryonic polarity by antagonizing Nodal signaling, thereby helping to restrict primitive streak formation to appropriate regions of the mouse embryo. Early asymmetric expression of Lefty in the inner cell mass also contributes to anterior–posterior axis specification during peri‐implantation and early gastrulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional work has revealed that epigenetic mechanisms intersect with Lefty–Nodal signaling to orchestrate embryogenesis and cell fate decisions. Studies report that TET‐mediated oxidation of 5‐methylcytosine is essential for proper Lefty expression, thereby balancing Nodal activity, while investigations in reproductive tissues underscore the dynamic regulation of Lefty during decidualization and stem cell maintenance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, a further set of studies extends the functional repertoire of Lefty beyond early development, indicating that it modulates diverse pathological states including fibrosis, epithelial–mesenchymal transition, and aberrant cell proliferation in contexts such as renal injury, cardiac remodeling, and even tumor growth. For instance, by attenuating both Smad‐dependent and MAPK pathways, Lefty can reduce fibroblast activation and limit fibrosis in kidney and myocardium, and influence pancreatic cell expansion during islet regeneration. Collectively, these findings position Lefty as a pivotal modulator of TGF‐β–related pathways in tissue remodeling and disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "16"}]}, {"type": "t", "text": " Importantly, however, none of these abstracts address or mention OR10V2P; as such, while the Lefty proteins are well characterized in these studies, the functional role of OR10V2P in these contexts remains unreported and appears to be unrelated to the highlighted developmental and pathophysiological processes.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Aitana Perea-Gomez, Francis D J Vella, William Shawlot, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The mouse embryo autonomously acquires anterior-posterior polarity at implantation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2006.02.017"}], "href": "https://doi.org/10.1016/j.devcel.2006.02.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16580991"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16580991"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Katsuyoshi Takaoka, Hiromi Nishimura, Hiroshi Hamada "}, {"type": "b", "children": [{"type": "t", "text": "Both Nodal signalling and stochasticity select for prospective distal visceral endoderm in mouse embryos."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-017-01625-x"}], "href": "https://doi.org/10.1038/s41467-017-01625-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29138408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29138408"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Meiyi Tang, Yun Xu, Joanne Julian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lefty is expressed in mouse endometrium in estrous cycle and peri-implantation period."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/deh717"}], "href": "https://doi.org/10.1093/humrep/deh717"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15640253"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15640253"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Meiyi Tang, Anatoly Mikhailik, Ilse Pauli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decidual differentiation of stromal cells promotes Proprotein Convertase 5/6 expression and lefty processing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2005-0684"}], "href": "https://doi.org/10.1210/en.2005-0684"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16141390"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16141390"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Meiyi Tang, Devendra Naidu, Patrick Hearing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LEFTY, a member of the transforming growth factor-beta superfamily, inhibits uterine stromal cell differentiation: a novel autocrine role."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2009-1081"}], "href": "https://doi.org/10.1210/en.2009-1081"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20056823"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20056823"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hai-Qiang Dai, Bang-An Wang, Lu Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature20095"}], "href": "https://doi.org/10.1038/nature20095"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27760115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27760115"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Toma Yakulov, Angelo Raggioli, Henriette Franz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Wnt3a-dependent and -independent protein interaction networks of chromatin-bound β-catenin in mouse embryonic stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Proteomics (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/mcp.M112.026914"}], "href": "https://doi.org/10.1074/mcp.M112.026914"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23592333"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23592333"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Gaétan Mayer, Josée Hamelin, Marie-Claude Asselin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The regulated cell surface zymogen activation of the proprotein convertase PC5A directs the processing of its secretory substrates."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M708763200"}], "href": "https://doi.org/10.1074/jbc.M708763200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18039650"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18039650"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "You-Qing Zhang, Lori Sterling, Aleksandr Stotland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nodal and lefty signaling regulates the growth of pancreatic cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Dyn (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/dvdy.21527"}], "href": "https://doi.org/10.1002/dvdy.21527"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18393305"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18393305"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Hidetaka Shiratori, Hiroshi Hamada "}, {"type": "b", "children": [{"type": "t", "text": "TGFβ signaling in establishing left-right asymmetry."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Semin Cell Dev Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.semcdb.2014.03.029"}], "href": "https://doi.org/10.1016/j.semcdb.2014.03.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24704359"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24704359"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Zhiwei Zhang, Tao Jiang, Quanlin Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nodal activates smad and extracellular signal-regulated kinases 1/2 pathways promoting renal cell carcinoma proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2015.3343"}], "href": "https://doi.org/10.3892/mmr.2015.3343"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25672326"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25672326"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Changgeng Xu, Mingwei Xu, Wei Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lefty1 alleviates renal tubulointerstitial injury in mice with unilateral ureteral obstruction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2015.4631"}], "href": "https://doi.org/10.3892/mmr.2015.4631"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26647776"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26647776"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Lijun Zhang, Changgeng Xu, Wei Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Anti-inflammatory effects of Lefty-1 in renal tubulointerstitial inflammation via regulation of the NF-κB pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijmm.2017.3327"}], "href": "https://doi.org/10.3892/ijmm.2017.3327"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29286065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29286065"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Lijun Zhang, Xiaohua Liu, Jun Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lefty-1 inhibits renal epithelial-mesenchymal transition by antagonizing the TGF-β/Smad signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Histol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10735-020-09859-8"}], "href": "https://doi.org/10.1007/s10735-020-09859-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32065356"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32065356"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Chang-Yi Li, Jing-Rui Zhang, Xin-Xin Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lefty1 Ameliorates Post-infarction Fibrosis by Suppressing p-Smad2 and p-ERK1/2 Signaling Pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cardiovasc Transl Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12265-020-10089-2"}], "href": "https://doi.org/10.1007/s12265-020-10089-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33409963"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33409963"}]}]}]}