Minute-cadence Observations of the LAMOST Fields with the TMTS: III. Statistic Study of the Flare Stars from the First Two Years

Tsinghua University-Ma Huateng Telescopes for Survey (TMTS) aims to detect fast-evolving transients in the Universe, which has led to the discovery of thousands of short-period variables and eclipsing binaries since 2020. In this paper, we present the observed properties of 125 flare stars identified by the TMTS within the first two years, with an attempt to constrain their eruption physics. As expected, most of these flares were recorded in late-type red stars with $G_{\rm BP}-G_{\rm RP}$ > 2.0 mag, however, the flares associated with bluer stars tend to be on average more energetic and have broader profiles. The peak flux (F_peak) of the flare is found to depend strongly on the equivalent duration (ED) of the energy release, i.e., $F_{{\rm peak}} \propto {\rm ED}^{0.72\pm0.04}$, which is consistent with results derived from the Kepler and Evryscope samples. This relation is likely related to the magnetic loop emission, while -- for the more popular non-thermal electron heating model -- a specific time evolution may be required to generate this relation. We notice that flares produced by hotter stars have a flatter $F_{{\rm peak}} \propto {\rm ED}$ relation compared to that from cooler stars. This is related to the statistical discrepancy in light-curve shape of flare events with different colors. In spectra from LAMOST, we find that flare stars have apparently stronger H alpha emission than inactive stars, especially at the low temperature end, suggesting that chromospheric activity plays an important role in producing flares. On the other hand, the subclass having frequent flares are found to show H alpha emission of similar strength in their spectra to that recorded with only a single flare but similar effective temperature, implying that the chromospheric activity may not be the only trigger for eruptions.Comment: 17 pages, 15 figures, 2 tables, refereed version. For associated data files, see https://cdsarc.cds.unistra.fr/viz-bin/cat/J/MNRAS/523/219

Endocytic regulation of alkali metal transport proteins in mammals, yeast and plants

The relative concentrations of ions and solutes inside cells are actively maintained by several classes of transport proteins, in many cases against their concentration gradient. These transport processes, which consume a large portion of cellular energy, must be constantly regulated. Many structurally distinct families of channels, carriers, and pumps have been characterized in considerable detail during the past decades and defects in the function of some of these proteins have been linked to a growing list of human diseases. The dynamic regulation of the transport proteins present at the cell surface is vital for both normal cellular function and for the successful adaptation to changing environments. The composition of proteins present at the cell surface is controlled on both the transcriptional and post-translational level. Post-translational regulation involves highly conserved mechanisms of phosphorylation- and ubiquitylation-dependent signal transduction routes used to modify the cohort of receptors and transport proteins present under any given circumstances. In this review, we will summarize what is currently known about one facet of this regulatory process: the endocytic regulation of alkali metal transport proteins. The physiological relevance, major contributors, parallels and missing pieces of the puzzle in mammals, yeast and plants will be discussed.This work was supported by grant BFU2011-30197-C03-03 from the Ministerio de Ciencia e Innovacion (Spain). V.L.-T. is supported by a fellowship from the Universidad Politecnica de Valencia. C. P. is supported by a fellowship from the Consejo Superior de Investigaciones Cientificas (Spain).Mulet Salort, JM.; Llopis Torregrosa, V.; Primo Planta, C.; Marques Romero, MC.; Yenush, L. (2013). Endocytic regulation of alkali metal transport proteins in mammals, yeast and plants. Current Genetics. 59(4):207-230. https://doi.org/10.1007/s00294-013-0401-2S207230594Abe F, Iida H (2003) Pressure-induced differential regulation of the two tryptophan permeases Tat1 and Tat2 by ubiquitin ligase Rsp5 and its binding proteins, Bul1 and Bul2. Mol Cell Biol 23:7566–7584Abriel H, Loffing J, Rebhun JF, Pratt JH, Schild L, Horisberger JD, Rotin D, Staub O (1999) Defective regulation of the epithelial Na+ channel by Nedd4 in Liddle’s syndrome. J Clin Invest 103:667–673. doi: 10.1172/JCI5713Alesutan I, Munoz C, Sopjani M, Dërmaku-Sopjani M, Michael D, Fraser S, Kemp BE, Seebohm G, Föller M, Lang F (2011) Inhibition of Kir2.1 (KCNJ2) by the AMP-activated protein kinase. Biochem Biophys Res Commun 408:505–510. doi: 10.1016/j.bbrc.2011.04.015Alvarez CE (2008) On the origins of arrestin and rhodopsin. BMC Evol Biol 8:222. doi: 10.1186/1471-2148-8-222Amerik AY, Nowak J, Swaminathan S, Hochstrasser M (2000) The Doa4 deubiquitinating enzyme is functionally linked to the vacuolar protein-sorting and endocytic pathways. Mol Biol Cell 11:3365–3380Anderson JA, Huprikar SS, Kochian LV, Lucas WJ, Gaber RF (1992) Functional expression of a probable Arabidopsis thaliana potassium channel in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 89:3736–3740Anderson JA, Nakamura RL, Gaber RF (1994) Heterologous expression of K+ channels in Saccharomyces cerevisiae: strategies for molecular analysis of structure and function. Symp Soc Exp Biol 48:85–97Aniento F, Gu F, Parton RG, Gruenberg J (1996) An endosomal beta COP is involved in the pH-dependent formation of transport vesicles destined for late endosomes. J Cell Biol 133:29–41Apse MP, Aharon GS, Snedden WA, Blumwald E (1999) Salt tolerance conferred by overexpression of a vacuolar Na+/H+ antiport in Arabidopsis. Science 285:1256–1258Arino J, Ramos J, Sychrova H (2010) Alkali metal cation transport and homeostasis in yeasts. Microbiol mol biol rev 74:95–120. doi: 10.1128/mmbr.00042-09Arnason TG, Pisclevich MG, Dash MD, Davies GF, Harkness TA (2005) Novel interaction between Apc5p and Rsp5p in an intracellular signaling pathway in Saccharomyces cerevisiae. Eukaryot Cell 4:134–146. doi: 10.1128/EC.4.1.134-146.2005Arroyo JP, Lagnaz D, Ronzaud C, Vázquez N, Ko BS, Moddes L, Ruffieux-Daidié D, Hausel P, Koesters R, Yang B, Stokes JB, Hoover RS, Gamba G, Staub O (2011) Nedd4-2 modulates renal Na+ –Cl– cotransporter via the aldosterone-SGK1-Nedd4-2 pathway. J Am Soc Nephrol 22:1707–1719. doi: 10.1681/ASN.2011020132Azmi IF, Davies BA, Xiao J, Babst M, Xu Z, Katzmann DJ (2008) ESCRT-III family members stimulate Vps4 ATPase activity directly or via Vta1. Dev Cell 14:50–61. doi: 10.1016/j.devcel.2007.10.021Babst M, Katzmann DJ, Estepa-Sabal EJ, Meerloo T, Emr SD (2002a) Escrt-III: an endosome-associated heterooligomeric protein complex required for mvb sorting. Dev Cell 3:271–282Babst M, Katzmann DJ, Snyder WB, Wendland B, Emr SD (2002b) Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body. Dev Cell 3:283–289Bache KG, Slagsvold T, Cabezas A, Rosendal KR, Raiborg C, Stenmark H (2004) The growth-regulatory protein HCRP1/hVps37A is a subunit of mammalian ESCRT-I and mediates receptor down-regulation. Mol Biol Cell 15:4337–4346. doi: 10.1091/mbc.E04-03-0250Baietti MF, Zhang Z, Mortier E, Melchior A, Degeest G, Geeraerts A, Ivarsson Y, Depoortere F, Coomans C, Vermeiren E, Zimmermann P, David G (2012) Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol 14:677–685. doi: 10.1038/ncb2502Barajas D, Nagy PD (2010) Ubiquitination of tombusvirus p33 replication protein plays a role in virus replication and binding to the host Vps23p ESCRT protein. Virology 397:358–368. doi: 10.1016/j.virol.2009.11.010Barajas D, Jiang Y, Nagy PD (2009) A unique role for the host ESCRT proteins in replication of Tomato bushy stunt virus. PLoS Pathog 5:e1000705. doi: 10.1371/journal.ppat.1000705Barberon M, Zelazny E, Robert S, Conéjéro G, Curie C, Friml J, Vert G (2011) Monoubiquitin-dependent endocytosis of the iron-regulated transporter 1 (IRT1) transporter controls iron uptake in plants. Proc Natl Acad Sci USA 108:E450–E458. doi: 10.1073/pnas.1100659108Barragán V, Leidi EO, Andrés Z, Rubio L, De Luca A, Fernández JA, Cubero B, Pardo JM (2012) Ion exchangers NHX1 and NHX2 mediate active potassium uptake into vacuoles to regulate cell turgor and stomatal function in Arabidopsis. Plant Cell 24:1127–1142. doi: 10.1105/tpc.111.095273Bassil E, Ohto MA, Esumi T, Tajima H, Zhu Z, Cagnac O, Belmonte M, Peleg Z, Yamaguchi T, Blumwald E (2011) The Arabidopsis intracellular Na+/H+ antiporters NHX5 and NHX6 are endosome associated and necessary for plant growth and development. Plant Cell 23:224–239. doi: 10.1105/tpc.110.079426Beaudenon SL, Huacani MR, Wang G, McDonnell DP, Huibregtse JM (1999) Rsp5 ubiquitin-protein ligase mediates DNA damage-induced degradation of the large subunit of RNA polymerase II in Saccharomyces cerevisiae. Mol Cell Biol 19:6972–6979Becuwe M, Vieira N, Lara D, Gomes-Rezende J, Soares-Cunha C, Casal M, Haguenauer-Tsapis R, Vincent O, Paiva S, Léon S (2012) A molecular switch on an arrestin-like protein relays glucose signaling to transporter endocytosis. J Cell Biol 196:247–259. doi: 10.1083/jcb.201109113Belgareh-Touzé N, Léon S, Erpapazoglou Z, Stawiecka-Mirota M, Urban-Grimal D, Haguenauer-Tsapis R (2008) Versatile role of the yeast ubiquitin ligase Rsp5p in intracellular trafficking. Biochem Soc Trans 36:791–796. doi: 10.1042/BST0360791Bhalla V, Oyster NM, Fitch AC, Wijngaarden MA, Neumann D, Schlattner U, Pearce D, Hallows KR (2006) AMP-activated kinase inhibits the epithelial Na+ channel through functional regulation of the ubiquitin ligase Nedd4-2. J Biol Chem 281:26159–26169. doi: 10.1074/jbc.M606045200Blondel MO, Morvan J, Dupre S, Urban-Grimal D, Haguenauer-Tsapis R, Volland C (2004) Direct sorting of the yeast uracil permease to the endosomal system is controlled by uracil binding and Rsp5p-dependent ubiquitylation. Mol Biol Cell 15:883–895. doi: 10.1091/mbc.E03-04-0202Boase NA, Rychkov GY, Townley SL, Dinudom A, Candi E, Voss AK, Tsoutsman T, Semsarian C, Melino G, Koentgen F, Cook DI, Kumar S (2011) Respiratory distress and perinatal lethality in Nedd4-2-deficient mice. Nat Commun 2:287. doi: 10.1038/ncomms1284Boehmer C, Laufer J, Jeyaraj S, Klaus F, Lindner R, Lang F, Palmada M (2008) Modulation of the voltage-gated potassium channel Kv1.5 by the SGK1 protein kinase involves inhibition of channel ubiquitination. Cell Physiol Biochem 22:591–600. doi: 10.1159/000185543Bonifacino JS, Traub LM (2003) Signals for sorting of transmembrane proteins to endosomes and lysosomes. Annu Rev Biochem 72:395–447. doi: 10.1146/annurev.biochem.72.121801.161800Bowers K, Levi BP, Patel FI, Stevens TH (2000) The sodium/proton exchanger Nhx1p is required for endosomal protein trafficking in the yeast Saccharomyces cerevisiae. Mol Biol Cell 11:4277–4294Brett CL, Tukaye DN, Mukherjee S, Rao R (2005) The yeast endosomal Na+K+/H+ exchanger Nhx1 regulates cellular pH to control vesicle trafficking. Mol Biol Cell 16:1396–1405. doi: 10.1091/mbc.E04-11-0999Cao XR, Lill NL, Boase N, Shi PP, Croucher DR, Shan H, Qu J, Sweezer EM, Place T, Kirby PA, Daly RJ, Kumar S, Yang B (2008) Nedd4 controls animal growth by regulating IGF-1 signaling. Sci Signal 1:ra5. doi: 10.1126/scisignal.1160940Carrasquillo R, Tian D, Krishna S, Pollak MR, Greka A, Schlöndorff J (2012) SNF8, a member of the ESCRT-II complex, interacts with TRPC6 and enhances its channel activity. BMC Cell Biol 13:33. doi: 10.1186/1471-2121-13-33Chen L, Hellmann H (2013) Plant E3 Ligases: flexible enzymes in a sessile world1. Mol Plant. doi: 10.1093/mp/sst005Chinchilla D, Zipfel C, Robatzek S, Kemmerling B, Nürnberger T, Jones JD, Felix G, Boller T (2007) A flagellin-induced complex of the receptor FLS2 and BAK1 initiates plant defence. Nature 448:497–500. doi: 10.1038/nature05999Christie KJ, Martinez JA, Zochodne DW (2012) Disruption of E3 ligase NEDD4 in peripheral neurons interrupts axon outgrowth: linkage to PTEN. Mol Cell Neurosci 50:179–192. doi: 10.1016/j.mcn.2012.04.006Clague MJ, Liu H, Urbé S (2012) Governance of endocytic trafficking and signaling by reversible ubiquitylation. Dev Cell 23:457–467. doi: 10.1016/j.devcel.2012.08.011Clancy JL, Henderson MJ, Russell AJ, Anderson DW, Bova RJ, Campbell IG, Choong DY, Macdonald GA, Mann GJ, Nolan T, Brady G, Olopade OI, Woollatt E, Davies MJ, Segara D, Hacker NF, Henshall SM, Sutherland RL, Watts CK (2003) EDD, the human orthologue of the hyperplastic discs tumour suppressor gene, is amplified and overexpressed in cancer. Oncogene 22:5070–5081. doi: 10.1038/sj.onc.1206775Coonrod EM, Stevens TH (2010) The yeast vps class E mutants: the beginning of the molecular genetic analysis of multivesicular body biogenesis. Mol Biol Cell 21:4057–4060. doi: 10.1091/mbc.E09-07-0603Crespo JL, Daicho K, Ushimaru T, Hall MN (2001) The GATA transcription factors GLN3 and GAT1 link TOR to salt stress in Saccharomyces cerevisiae. J Biol Chem 276:34441–34444. doi: 10.1074/jbc.M103601200Debonneville C, Flores SY, Kamynina E, Plant PJ, Tauxe C, Thomas MA, Münster C, Chraïbi A, Pratt JH, Horisberger JD, Pearce D, Loffing J, Staub O (2001) Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression. EMBO J 20:7052–7059. doi: 10.1093/emboj/20.24.7052Downes BP, Stupar RM, Gingerich DJ, Vierstra RD (2003) The HECT ubiquitin-protein ligase (UPL) family in Arabidopsis: UPL3 has a specific role in trichome development. Plant J 35:729–742Eisenach C, Chen ZH, Grefen C, Blatt MR (2012) The trafficking protein SYP121 of Arabidopsis connects programmed stomatal closure and K+ channel activity with vegetative growth. Plant J 69:241–251. doi: 10.1111/j.1365-313X.2011.04786.xEkberg J, Schuetz F, Boase NA, Conroy SJ, Manning J, Kumar S, Poronnik P, Adams DJ (2007) Regulation of the voltage-gated K(+) channels KCNQ2/3 and KCNQ3/5 by ubiquitination. Novel role for Nedd4-2. J Biol Chem 282:12135–12142. doi: 10.1074/jbc.M609385200Faresse N, Lagnaz D, Debonneville A, Ismailji A, Maillard M, Fejes-Toth G, Náray-Fejes-Tóth A, Staub O (2012) Inducible kidney-specific Sgk1 knockout mice show a salt-losing phenotype. Am J Physiol Renal Physiol 302:F977–F985. doi: 10.1152/ajprenal.00535.2011Field MC, Gabernet-Castello C, Dacks JB (2007) Reconstructing the evolution of the endocytic system: insights from genomics and molecular cell biology. Adv Exp Med Biol 607:84–96. doi: 10.1007/978-0-387-74021-8_7Fisk HA, Yaffe MP (1999) A role for ubiquitination in mitochondrial inheritance in Saccharomyces cerevisiae. J Cell Biol 145:1199–1208Flinn RJ, Yan Y, Goswami S, Parker PJ, Backer JM (2010) The late endosome is essential for mTORC1 signaling. Mol Biol Cell 21:833–841. doi: 10.1091/mbc.E09-09-0756Fotia AB, Ekberg J, Adams DJ, Cook DI, Poronnik P, Kumar S (2004) Regulation of neuronal voltage-gated sodium channels by the ubiquitin-protein ligases Nedd4 and Nedd4-2. J Biol Chem 279:28930–28935. doi: 10.1074/jbc.M402820200Futter CE, White IJ (2007) Annexins and endocytosis. Traffic 8:951–958. doi: 10.1111/j.1600-0854.2007.00590.xGabriely G, Kama R, Gerst JE (2007) Involvement of specific COPI subunits in protein sorting from the late endosome to the vacuole in yeast. Mol Cell Biol 27:526–540. doi: 10.1128/MCB.00577-06Gajewska B, Shcherbik N, Oficjalska D, Haines DS, Zoladek T (2003) Functional analysis of the human orthologue of the RSP5-encoded ubiquitin protein ligase, hNedd4, in yeast. Curr Genet 43:1–10. doi: 10.1007/s00294-003-0371-xGalan JM, Moreau V, Andre B, Volland C, Haguenauer-Tsapis R (1996) Ubiquitination mediated by the Npi1p/Rsp5p ubiquitin-protein ligase is required for endocytosis of the yeast uracil permease. J Biol Chem 271:10946–10952Gao T, Liu Z, Wang Y, Cheng H, Yang Q, Guo A, Ren J, Xue Y (2013) UUCD: a family-based database of ubiquitin and ubiquitin-like conjugation. Nucleic Acids Res 41:D445–D451. doi: 10.1093/nar/gks1103Geldner N (2004) The plant endosomal system—its structure and role in signal transduction and plant development. Planta 219:547–560. doi: 10.1007/s00425-004-1302-xGitan RS, Eide DJ (2000) Zinc-regulated ubiquitin conjugation signals endocytosis of the yeast ZRT1 zinc transporter. Biochem J 346:329–336. doi: 10.1042/0264-6021:3460329Gitan RS, Luo H, Rodgers J, Broderius M, Eide D (1998) Zinc-induced inactivation of the yeast ZRT1 zinc transporter occurs through endocytosis and vacuolar degradation. J Biol Chem 273:28617–28624Gómez-Gómez L, Boller T (2000) FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis. Mol Cell 5:1003–1011Gong X, Chang A (2001) A mutant plasma membrane ATPase, Pma1-10, is defective in stability at the yeast cell surface. Proc Natl Acad Sci USA 98:9104–9109. doi: 10.1073/pnas.161282998Guo J, Wang T, Li X, Shallow H, Yang T, Li W, Xu J, Fridman MD, Yang X, Zhang S (2012) Cell surface expression of human ether-a-go–go-related gene (hERG) channels is regulated by caveolin-3 protein via the ubiquitin ligase Nedd4-2. J Biol Chem 287:33132–33141. doi: 10.1074/jbc.M112.389643Gwizdek C, Hobeika M, Kus B, Ossareh-Nazari B, Dargemont C, Rodriguez MS (2005) The mRNA nuclear export factor Hpr1 is regulated by Rsp5-mediated ubiquitylation. J Biol Chem 280:13401–13405. doi: 10.1074/jbc.C500040200Haas TJ, Sliwinski MK, Martínez DE, Preuss M, Ebine K, Ueda T, Nielsen E, Odorizzi G, Otegui MS (2007) The Arabidopsis AAA ATPase SKD1 is involved in multivesicular endosome function and interacts with its positive regulator LYST-INTERACTING PROTEIN5. Plant Cell 19:1295–1312. doi: 10.1105/tpc.106.049346Harkness TA, Davies GF, Ramaswamy V, Arnason TG (2002) The ubiquitin-dependent targeting pathway in Saccharomyces cerevisiae plays a critical role in multiple chromatin assembly regulatory steps. Genetics 162:615–632Hasenbrink G, Schwarzer S, Kolacna L, Ludwig J, Sychrova H, Lichtenberg-Fraté H (2005) Analysis of the mKir2.1 channel activity in potassium influx defective Saccharomyces cerevisiae strains determined as changes in growth characteristics. FEBS Lett 579:1723–1731. doi: 10.1016/j.febslet.2005.02.025Hatakeyama R, Kamiya M, Takahara T, Maeda T (2010) Endocytosis of the aspartic acid/glutamic acid transporter Dip5 is triggered by substrate-dependent recruitment of the Rsp5 ubiquitin ligase via the arrestin-like protein Aly2. Mol Cell Biol 30:5598–5607. doi: 10.1128/MCB.00464-10Hayashi M, Fukuzawa T, Sorimachi H, Maeda T (2005) Constitutive activation of the pH-responsive Rim101 pathway in yeast mutants defective in late steps of the MVB/ESCRT pathway. Mol Cell Biol 25:9478–9490. doi: 10.1128/mcb.25.21.9478-9490.2005He P, Lee SJ, Lin S, Seidler U, Lang F, Fejes-Toth G, Naray-Fejes-Toth A, Yun CC (2011) Serum- and glucocorticoid-induced kinase 3 in recycling endosomes mediates acute activation of Na+/H+ exchanger NHE3 by glucocorticoids. Mol Biol Cell 22:3812–3825. doi: 10.1091/mbc.E11-04-0328Heese A, Hann DR, Gimenez-Ibanez S, Jones AM, He K, Li J, Schroeder JI, Peck SC, Rathjen JP (2007) The receptor-like kinase SERK3/BAK1 is a central regulator of innate immunity in plants. Proc Natl Acad Sci USA 104:12217–12222. doi: 10.1073/pnas.0705306104Hein C, Springael JY, Volland C, Haguenauer-Tsapis R, André B (1995) NPl1, an essential yeast gene involved in induced degradation of Gap1 and Fur4 permeases, encodes the Rsp5 ubiquitin-protein ligase. Mol Microbiol 18:77–87Henke G, Maier G, Wallisch S, Boehmer C, Lang F (2004) Regulation of the voltage gated K+ channel Kv1.3 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid inducible kinase SGK1. J Cell Physiol 199:194–199. doi: 10.1002/jcp.10430Herberth S, Shahriari M, Bruderek M, Hessner F, Müller B, Hülskamp M, Schellmann S (2012) Artificial ubiquitylation is sufficient for sorting of a plasma membrane ATPase to the vacuolar lumen of Arabidopsis cells. Planta 236:63–77. doi: 10.1007/s00425-012-1587-0Hicke L, Dunn R (2003) Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. Annu Rev Cell Dev Biol 19:141–172. doi: 10.1146/annurev.cellbio.19.110701.154617Hicke L, Riezman H (1996) Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis. Cell 84:277–287Hicke L, Zanolari B, Riezman H (1998) Cytoplasmic tail phosphorylation of the alpha-factor receptor is required for its ubiquitination and internalization. J Cell Biol 141:349–358Hoppe T, Matuschewski K, Rape M, Schlenker S, Ulrich HD, Jentsch S (2000) Activation of a membrane-bound transcription factor by regulated ubiquitin/proteasome-dependent processing. Cell 102:577–586Hsu C, Morohashi Y, Yoshimura S, Manrique-Hoyos N, Jung S, Lauterbach MA, Bakhti M, Grønborg M, Möbius W, Rhee J, Barr FA, Simons M (2010) Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C. J Cell Biol 189:223–232. doi: 10.1083/jcb.200911018Hu G, Caza M, Cadieux B, Chan V, Liu V, Kronstad J (2013) Cryptococcus neoformans requires the ESCRT protein Vps23 for iron acquisition from heme, for capsule formation, and for virulence. Infect Immun 81:292–302. doi: 10.1128/IAI.01037-12Huang F, Kirkpatrick D, Jiang X, Gygi S, Sorkin A (2006) Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell 21:737–748. doi: 10.1016/j.molcel.2006.02.018Huang F, Goh LK, Sorkin A (2007) EGF receptor ubiquitination is not necessary for its internalization. Proc Natl Acad Sci USA 104:16904–16909. doi: 10.1073/pnas.0707416104Huibregtse JM, Scheffner M, Beaudenon S, Howley PM (1995) A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc Natl Acad Sci USA 92:2563–2567Hurst AC, Meckel T, Tayefeh S, Thiel G, Homann U (2004) Trafficking of the plant potassium inward rectifier KAT1 in guard cell protoplasts of Vicia faba. Plant J 37:391–397Husnjak K, Dikic I (2012) Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions. Annu Rev Biochem 81:291–322. doi: 10.1146/annurev-biochem-051810-094654Ibl V, Csaszar E, Schlager N, Neubert S, Spitzer C, Hauser MT (2012) Interactome of the plant-specific ESCRT-III component AtVPS2.2 in Arabidopsis thaliana. J Proteome Res 11:397–411. doi: 10.1021/pr200845nIchimura T, Yamamura H, Sasamoto K, Tominaga Y, Taoka M, Kakiuchi K, Shinkawa T, Takahashi N, Shimada S, Isobe T (2005) 14-3-3 proteins modulate the expression of epithelial Na + channels by phosphorylation-dependent interaction with Nedd4-2 ubiquitin ligase. J Biol Chem 280:13187–13194. doi: 10.1074/jbc.M412884200Jegla TJ, Zmasek CM, Batalov S, Nayak SK (2009) Evolution of the human ion channel set. Comb Chem High Throughput Screen 12:2–23Jenness DD, Li Y, Tipper C, Spatrick P (1997) Elimination of defective alpha-factor pheromone receptors. Mol Cell Biol 17:6236–6245Jespersen T, Membrez M, Nicolas CS, Pitard B, Staub O, Olesen SP, Baró I, Abriel H (2007) The KCNQ1 potassium channel is down-regulated by ubiquitylating enzymes of the Nedd4/Nedd4-like family. Cardiovasc Res 74:64–74. doi: 10.1016/j.cardiores.2007.01.008Jolliffe CN, Harvey KF, Haines BP, Parasivam G, Kumar S (2000) Identification of multiple proteins expressed in murine embryos as binding partners for the WW domains of the ubiquitin-protein ligase Nedd4. Biochem J 351(Pt 3):557–565Kallay LM, Brett CL, Tukaye DN, Wemmer MA, Chyou A, Odorizzi G, Rao R (2011) Endosomal Na+(K+)/H+ exchanger Nhx1/Vps44 functions independently and downstream of multivesicular body formation. J Biol Chem 286:44067–44077. doi: 10.1074/jbc.M111.282319Kamsteeg EJ, Savelkoul PJ, Hendriks G, Konings IB, Nivillac NM, Lagendijk AK, van der Sluijs P, Deen PM (2008) Missorting of the Aquaporin-2 mutant E258K to multivesicular bodies/lysosomes in dominant NDI is associated with its monoubiquitination and increased phosphoryla

Association between fibre intake and indoxyl sulphate/P-cresyl sulphate in patients with chronic kidney disease: meta-analysis and systematic review of experimental studies

Background and objective: Indoxyl sulphate (IS) and p-cresyl sulphate (PCS), which are difficult to excrete adequately out of the body, are closely related to the progression of chronic kidney disease (CKD) and various deuteropathy. Better than peritoneal dialysis (PD) and haemodialysis (HD), dietary fibre has been considered to reduce IS and PCS levels. In view of the absence of formal recommendations on fibre intake in CKD nutritional guidelines, we conducted this meta-analysis to assess the effects of dietary fibre on IS and PCS for CKD patients. Methods: The effects were pooled and expressed in terms of weighted mean difference (WMD) with 95% confidence interval (95% CI). Q test and I2 statistics were used to assess the heterogeneity. Results: A total of 12 relevant estimates from 7 reports, including 203 CKD patients, showed that dietary fibre significantly reduced their PCS level (WMD = −16.160, 95% CI: −23.824, −8.495). Conclusions: The meta-analysis produced a strong corroboration that dietary fibre intake does have a good therapeutic effect on patients with CKD. The conclusions need to be validated by randomised controlled experiments (RCT) with better design, larger samples, longer course of treatment and higher quality

Decoding the tumor microenvironment and molecular mechanism: unraveling cervical cancer subpopulations and prognostic signatures through scRNA-Seq and bulk RNA-seq analyses

BackgroundCervical carcinoma (CC) represents a prevalent gynecological neoplasm, with a discernible rise in prevalence among younger cohorts observed in recent years. Nonetheless, the intrinsic cellular heterogeneity of CC remains inadequately investigated.MethodsWe utilized single-cell RNA sequencing (scRNA-seq) transcriptomic analysis to scrutinize the tumor epithelial cells derived from four specimens of cervical carcinoma (CC) patients. This method enabled the identification of pivotal subpopulations of tumor epithelial cells and elucidation of their contributions to CC progression. Subsequently, we assessed the influence of associated molecules in bulk RNA sequencing (Bulk RNA-seq) cohorts and performed cellular experiments for validation purposes.ResultsThrough our analysis, we have discerned C3 PLP2+ Tumor Epithelial Progenitor Cells as a noteworthy subpopulation in cervical carcinoma (CC), exerting a pivotal influence on the differentiation and progression of CC. We have established an independent prognostic indicator—the PLP2+ Tumor EPCs score. By stratifying patients into high and low score groups based on the median score, we have observed that the high-score group exhibits diminished survival rates compared to the low-score group. The correlations observed between these groups and immune infiltration, enriched pathways, single-nucleotide polymorphisms (SNPs), drug sensitivity, among other factors, further underscore their impact on CC prognosis. Cellular experiments have validated the significant impact of ATF6 on the proliferation and migration of CC cell lines.ConclusionThis study enriches our comprehension of the determinants shaping the progression of CC, elevates cognizance of the tumor microenvironment in CC, and offers valuable insights for prospective CC therapies. These discoveries contribute to the refinement of CC diagnostics and the formulation of optimal therapeutic approaches

Multiwavelength observations of

Context.Swift J0243.6+6124 is a high-mass X-ray binary that went into a giant X-ray outburst in 2017. During this event, the X-ray luminosity reached the highest value ever measured in a galactic Be/X-ray binary. Aims. Our aim is to study the long-term variability of Swift J0243.6+6124 after the 2017 major X-ray outburst. Methods. We have obtained optical spectroscopy and photometry data during four years after the event. The long-term photometric light curve and the equivalent widths of the Hα and He I λ6678 lines were used to monitor the state of the Be star’s circumstellar disk. The Hα line profiles show evidence for V/R variability that was accounted for by fitting the Hα spectral line profile with two Gaussian functions. We divided our data into three phases according to the intensity of the X-ray, optical, and infrared emission. Results. Phase I covers the rise and decay of the giant X-ray outburst that took place in October–November 2017. We interpret phase II as the dissipation of the Be star’s equatorial disk and phase III as its recovery. The timescale of a complete formation and dissipation process is about 1250 days. The epoch when the dissipation process stopped and the reformation period began is estimated to be around MJD 58530. We find a delay of ∼100–200 days between the minimum of the optical or infrared intensity and the strength of the Hα line after the X-ray outburst, which may indicate that the dissipation of the disk begins from the inner parts. The motion of the density perturbation inside the disk is prograde, with a V/R quasi-period of about four years. The source shows a positive correlation in the (B − V) color index versus V-band magnitude diagram, which implies that the system is seen at a small or moderate inclination angle. Conclusions. Despite the super-Eddington X-ray luminosity during the outburst, the subsequent pattern of long-term optical and IR variability of Swift J0243.6+6124 is typical of Be/X-ray binaries

Association of walkability and NO2 with metabolic syndrome: A cohort study in China

Background: Epidemiological studies have reported an association between traffic-related pollution with risk of metabolic syndrome (MetS). However, evidence from prospective studies on the association of walkability and nitrogen dioxide (NO2) with MetS is still scarce. We, therefore, aimed to evaluate the association of long-term exposure to NO2 and walkability with hazards of incident MetS. Methods: A total of 17,965 participants without MetS diagnosed within one year at baseline were included in our study from a population-based prospective cohort in Yinzhou District, Ningbo, Zhejiang Province, China. Participants were followed up by the regional Health Information System (HIS) until December 15, 2021. MetS was defined based on the criteria of Chinese Diabetes Society (CDS2004). We used walkscore tools, calculating with amenity categories and decay functions, and spatial–temporal land-use regression (LUR) models to estimate walkability and NO2 concentrations. We used Cox proportional hazards regression models to examine the association of walkability and NO2 with hazards of MetS incidence reporting with hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Overall, we followed up 77,303 person-years and identified 4040 incident cases of MetS in the entire cohort. Higher walkability was inversely associated with incident MetS (HR = 0.94, 95 % CI: 0.91–0.99), whereas NO2 was positively associated with MetS incidence (HR = 1.07, 95 %CI: 1.00–1.15) per interquartile range increment in two-exposure models. Furthermore, we found a significant multiplicative interaction between walkability and NO2. Stronger associations were observed for NO2 and incident MetS among men, smokers, drinkers and participants who aged < 60 years and had higher levels of income. Conclusion: In summary, we found living in areas with lower walkability and higher concentrations of NO2 were associated with increased incidence of MetS. The beneficial effect of higher walkability may be attenuated by exposure to NO2

Image_2_Decoding the tumor microenvironment and molecular mechanism: unraveling cervical cancer subpopulations and prognostic signatures through scRNA-Seq and bulk RNA-seq analyses.tif

BackgroundCervical carcinoma (CC) represents a prevalent gynecological neoplasm, with a discernible rise in prevalence among younger cohorts observed in recent years. Nonetheless, the intrinsic cellular heterogeneity of CC remains inadequately investigated.MethodsWe utilized single-cell RNA sequencing (scRNA-seq) transcriptomic analysis to scrutinize the tumor epithelial cells derived from four specimens of cervical carcinoma (CC) patients. This method enabled the identification of pivotal subpopulations of tumor epithelial cells and elucidation of their contributions to CC progression. Subsequently, we assessed the influence of associated molecules in bulk RNA sequencing (Bulk RNA-seq) cohorts and performed cellular experiments for validation purposes.ResultsThrough our analysis, we have discerned C3 PLP2+ Tumor Epithelial Progenitor Cells as a noteworthy subpopulation in cervical carcinoma (CC), exerting a pivotal influence on the differentiation and progression of CC. We have established an independent prognostic indicator—the PLP2+ Tumor EPCs score. By stratifying patients into high and low score groups based on the median score, we have observed that the high-score group exhibits diminished survival rates compared to the low-score group. The correlations observed between these groups and immune infiltration, enriched pathways, single-nucleotide polymorphisms (SNPs), drug sensitivity, among other factors, further underscore their impact on CC prognosis. Cellular experiments have validated the significant impact of ATF6 on the proliferation and migration of CC cell lines.ConclusionThis study enriches our comprehension of the determinants shaping the progression of CC, elevates cognizance of the tumor microenvironment in CC, and offers valuable insights for prospective CC therapies. These discoveries contribute to the refinement of CC diagnostics and the formulation of optimal therapeutic approaches.</p

Table_1_Decoding the tumor microenvironment and molecular mechanism: unraveling cervical cancer subpopulations and prognostic signatures through scRNA-Seq and bulk RNA-seq analyses.docx

BackgroundCervical carcinoma (CC) represents a prevalent gynecological neoplasm, with a discernible rise in prevalence among younger cohorts observed in recent years. Nonetheless, the intrinsic cellular heterogeneity of CC remains inadequately investigated.MethodsWe utilized single-cell RNA sequencing (scRNA-seq) transcriptomic analysis to scrutinize the tumor epithelial cells derived from four specimens of cervical carcinoma (CC) patients. This method enabled the identification of pivotal subpopulations of tumor epithelial cells and elucidation of their contributions to CC progression. Subsequently, we assessed the influence of associated molecules in bulk RNA sequencing (Bulk RNA-seq) cohorts and performed cellular experiments for validation purposes.ResultsThrough our analysis, we have discerned C3 PLP2+ Tumor Epithelial Progenitor Cells as a noteworthy subpopulation in cervical carcinoma (CC), exerting a pivotal influence on the differentiation and progression of CC. We have established an independent prognostic indicator—the PLP2+ Tumor EPCs score. By stratifying patients into high and low score groups based on the median score, we have observed that the high-score group exhibits diminished survival rates compared to the low-score group. The correlations observed between these groups and immune infiltration, enriched pathways, single-nucleotide polymorphisms (SNPs), drug sensitivity, among other factors, further underscore their impact on CC prognosis. Cellular experiments have validated the significant impact of ATF6 on the proliferation and migration of CC cell lines.ConclusionThis study enriches our comprehension of the determinants shaping the progression of CC, elevates cognizance of the tumor microenvironment in CC, and offers valuable insights for prospective CC therapies. These discoveries contribute to the refinement of CC diagnostics and the formulation of optimal therapeutic approaches.</p