{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:04:24Z","timestamp":1789725864814,"version":"4.0.1"},"reference-count":64,"publisher":"National Academy of Sciences","issue":"13","license":[{"start":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T00:00:00Z","timestamp":1679356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008398","name":"Villum Fonden","doi-asserted-by":"publisher","award":["15365"],"award-info":[{"award-number":["15365"]}],"id":[{"id":"10.13039\/100008398","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004836","name":"Danmarks Frie Forskningsfond","doi-asserted-by":"publisher","award":["9064-00009B"],"award-info":[{"award-number":["9064-00009B"]}],"id":[{"id":"10.13039\/501100004836","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ragna Rask-Nielsens Foundation","award":["KH0622"],"award-info":[{"award-number":["KH0622"]}]},{"DOI":"10.13039\/501100002808","name":"Carlsbergfondet","doi-asserted-by":"publisher","award":["CF19-0353"],"award-info":[{"award-number":["CF19-0353"]}],"id":[{"id":"10.13039\/501100002808","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000581","name":"Carnegie Dunfermline Trust","doi-asserted-by":"publisher","award":["70425"],"award-info":[{"award-number":["70425"]}],"id":[{"id":"10.13039\/501100000581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000275","name":"Leverhulme Trust","doi-asserted-by":"publisher","award":["RPG-2019-167"],"award-info":[{"award-number":["RPG-2019-167"]}],"id":[{"id":"10.13039\/501100000275","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,3,28]]},"abstract":"<jats:p>\n                    More than half of all extant metazoan species on earth are insects. The evolutionary success of insects is linked with their ability to osmoregulate, suggesting that they have evolved unique physiological mechanisms to maintain water balance. In beetles (Coleoptera)\u2014the largest group of insects\u2014a specialized rectal (\u201ccryptonephridial\u201d) complex has evolved that recovers water from the rectum destined for excretion and recycles it back to the body. However, the molecular mechanisms underpinning the remarkable water-conserving functions of this system are unknown. Here, we introduce a transcriptomic resource, BeetleAtlas.org, for the exceptionally desiccation-tolerant red flour beetle\u00a0\n                    <jats:italic>Tribolium castaneum,<\/jats:italic>\n                    \u00a0and demonstrate its utility by identifying a cation\/H\n                    <jats:sup>+<\/jats:sup>\n                    \u00a0antiporter (NHA1) that is enriched and functionally significant in the\u00a0\n                    <jats:italic>Tribolium<\/jats:italic>\n                    \u00a0rectal complex. NHA1 localizes exclusively to a specialized cell type, the leptophragmata, in the distal region of the Malpighian tubules associated with the rectal complex. Computational modeling and electrophysiological characterization in\u00a0\n                    <jats:italic>Xenopus oocytes<\/jats:italic>\n                    \u00a0show that NHA1 acts as an electroneutral K\n                    <jats:sup>+<\/jats:sup>\n                    \/H\n                    <jats:sup>+<\/jats:sup>\n                    \u00a0antiporter. Furthermore, genetic silencing of\u00a0\n                    <jats:italic>Nha1<\/jats:italic>\n                    \u00a0dramatically increases excretory water loss and reduces organismal survival during desiccation stress, implying that NHA1 activity is essential for maintaining systemic water balance. Finally, we show that Tiptop, a conserved transcription factor, regulates NHA1 expression in leptophragmata and controls leptophragmata maturation, illuminating the developmental mechanism that establishes the functions of this cell. Together, our work provides\u00a0insights into the molecular architecture underpinning the function of one of the most powerful water-conserving mechanisms in nature,\u00a0the beetle rectal complex.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2217084120","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T13:34:32Z","timestamp":1679405672000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":37,"title":["NHA1 is a cation\/proton antiporter essential for the water-conserving functions of the rectal complex in\n                    <i>Tribolium castaneum<\/i>"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6225-9777","authenticated-orcid":false,"given":"Muhammad\u00a0T.","family":"Naseem","sequence":"first","affiliation":[{"name":"Department of Biology, Section for Cell and Neurobiology, University of Copenhagen, Copenhagen DK-2100, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5941-1187","authenticated-orcid":false,"given":"Robin","family":"Beaven","sequence":"additional","affiliation":[{"name":"Deanery of Biomedical Sciences, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH8 9AG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4203-114X","authenticated-orcid":false,"given":"Takashi","family":"Koyama","sequence":"additional","affiliation":[{"name":"Department of Biology, Section for Cell and Neurobiology, University of Copenhagen, Copenhagen DK-2100, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sehrish","family":"Naz","sequence":"additional","affiliation":[{"name":"Department of Biology, Section for Cell and Neurobiology, University of Copenhagen, Copenhagen DK-2100, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-yuan","family":"Su","sequence":"additional","affiliation":[{"name":"Deanery of Biomedical Sciences, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH8 9AG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0635-1843","authenticated-orcid":false,"given":"David\u00a0P.","family":"Leader","sequence":"additional","affiliation":[{"name":"Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"A.\u00a0Klaerke","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, Section for Pathobiological Sciences, University of Copenhagen DK-1870, Frederiksberg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1777-7938","authenticated-orcid":false,"given":"Kirstine","family":"Calloe","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, Section for Pathobiological Sciences, University of Copenhagen DK-1870, Frederiksberg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5785-2552","authenticated-orcid":false,"given":"Barry","family":"Denholm","sequence":"additional","affiliation":[{"name":"Deanery of Biomedical Sciences, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH8 9AG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5903-7196","authenticated-orcid":false,"given":"Kenneth\u00a0V.","family":"Halberg","sequence":"additional","affiliation":[{"name":"Department of Biology, Section for Cell and Neurobiology, University of Copenhagen, Copenhagen DK-2100, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,3,21]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-environ-012420-050035"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/9781119391128.ch4"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.90.1.1"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2806(08)60103-4"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00694153"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1964.0013"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1968.0004"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.128314"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1976.0043"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1910(85)90016-2"},{"key":"e_1_3_4_11_2","first-page":"R187","article-title":"Water vapor absorption in insects","volume":"244","author":"Machin J.","year":"1983","unstructured":"J. Machin, Water vapor absorption in insects. Am. J. Physiol. 244, R187\u2013R192 (1983).","journal-title":"Am. J. Physiol."},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.82.1.123"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00360-018-1164-3"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0040-8166(90)90053-C"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/225753a0"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx976"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa914"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M113.035600"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7007-10-90"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-12-296"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004270050269"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004270050268"},{"key":"e_1_3_4_23_2","first-page":"2832","article-title":"Efficient CRISPR-mediated gene targeting and transgene replacement in the beetle Tribolium castaneum","volume":"142","author":"Gilles A. F.","year":"2015","unstructured":"A. F. Gilles, J. B. Schinko, M. Averof, Efficient CRISPR-mediated gene targeting and transgene replacement in the beetle Tribolium castaneum. Development 142, 2832\u20132839 (2015).","journal-title":"Development"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)00666-8"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-022-01231-4"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13227-022-00201-9"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-019-6394-6"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1054"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2015.05.007"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2004-5-9-r69"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2311.1964.tb02302.x"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-1878(199908)21:8<637::AID-BIES3>3.0.CO;2-W"},{"key":"e_1_3_4_33_2","first-page":"137","article-title":"Sur la structure de la region cryptosol\u00e9ni\u00e9e chez les col\u00e9opt\u00e8res, Tenebrio molitor L. et Dermestes lardius L","volume":"23","author":"Lison L.","year":"1937","unstructured":"L. Lison, Sur la structure de la region cryptosol\u00e9ni\u00e9e chez les col\u00e9opt\u00e8res, Tenebrio molitor L. et Dermestes lardius L. Bull. Acad. R. Belg. 23, 137\u2013327 (1937).","journal-title":"Bull. Acad. R. Belg."},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","unstructured":"T. Koyama A unique Malpighian tubule architecture in Tribolium castaneum informs the evolutionary origins of systemic osmoregulation in beetles. Proc. Natl. Acad. Sci. U.S.A. 118 e2023314118 (2021). e2023314118","DOI":"10.1073\/pnas.2023314118"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.asd.2014.08.002"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.088989"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00360.2004"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1508031112"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/yea.799"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.007872"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3213"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.10286"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1982.tb01315.x"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.22.5860-5865.1998"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00823-9"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/0300-9629(86)90700-0"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.204.13.2331"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.00498"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25445-2"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinsphys.2014.05.023"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1139\/z85-282"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00335054"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinsphys.2011.12.009"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1817822116"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400782101"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047431"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-015-1880-y"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11266"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00018.2007"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-10-53"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7800"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.016"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008727"},{"key":"e_1_3_4_64_2","first-page":"1235","article-title":"Inorganic ion composition in Tardigrada: Cryptobionts contain a large fraction of unidentified organic solutes","volume":"216","author":"Halberg K. A.","year":"2013","unstructured":"K. A. Halberg, K. W. Larsen, A. J\u00f8rgensen, H. Raml\u00f8v, N. M\u00f8bjerg, Inorganic ion composition in Tardigrada: Cryptobionts contain a large fraction of unidentified organic solutes. J. Exp. Biol. 216, 1235\u20131243 (2013).","journal-title":"J. Exp. Biol."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2217084120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T08:42:25Z","timestamp":1695285745000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2217084120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,21]]},"references-count":64,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2023,3,28]]}},"alternative-id":["10.1073\/pnas.2217084120"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2217084120","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,21]]},"assertion":[{"value":"2022-10-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2217084120"}}