ライフサイエンスコーパス: actin

1 structure of CPEB3 and an actin filament (F-actin).

2 at were rescued by uncoupling VE-cadDEE from actin.

3 overs or blocks myosin binding sites along F-actin.

4 required to slow down the turnover of apical actin.

5 g regions, promoting myosin interaction with actin.

6 al N-BAR domain of ASAP1 directly binds to F-actin.

7 interaction with nucleotides and filamentous actin.

8 roteins, most such efforts have not targeted actin.

9 ized Spire on beads and added Cappuccino and actin.

10 rough a dynamic network of polymeric nuclear actin.

11 ases Rac and Rho are important regulators of actin.

12 lizes to the sarcomere and can directly bind actin.

13 ation and for maintaining normal levels of F-actin [8-10].

14 nstrate a surprising role for shuttling of F-actin across cells for lamellipodial expansion.

15 o suggest a reciprocal shift, with basal and actin-activated ATPase activity of IFI-3a showing reduce

16 Immunostaining with alpha-smooth muscle actin (alpha SMA) revealed a significant reduction in he

17 ibited greater levels of alpha-smooth muscle actin (alpha-SMA) expression, and exerted larger tractio

18 mic comparison of mature alpha-smooth muscle actin (alpha-SMA)+ myofibroblasts (verified by immunocyt

19 ne, ACTA2, which encodes alpha-smooth muscle actin (alpha-SMA).

20 n polymerization and the interaction between actin and actin-binding proteins.

21 this time the released heads remain close to actin and can quickly rebind, enhancing the force produc

22 Here we study the interaction between actin and CPEB3 and propose a molecular model for the co

23 inase (PI3K) inhibition results in loss of F-actin and expansion of apical-basal domains, which comes

24 Moreover, actin and microtubule depolymerization and changing chro

25 ), composed of F-actin, myosin II, and other actin and myosin II regulators.

26 now identified between tropomyosin and both actin and myosin.

27 Taken together, these findings place Rho-actin and NAD(+) upstream of spheroid formation and may

28 Interestingly, ccb also interacts with actin and the actin nucleator spire The data revealed th

29 The co-sedimentation of actin and tropomyosin showed weakening of actin-mutant t

30 ught residue-to-residue interactions between actin and tropomyosin.

31 We propose that communication between the actin- and nucleotide-binding regions of myosin assures

32 how myosin couples structural changes in the actin- and nucleotide-binding regions with force generat

33 s of Ena/VASP proteins reduced lamellipodial actin assembly and perturbed lamellipodial architecture,

34 ling of the fusogenic ectodomain to branched actin assembly is sufficient to drive cell-cell fusion.

35 sic domain of APC (APC-B) directly nucleates actin assembly, and this activity is required in vivo fo

36 rs Spire and Cappuccino synergize to promote actin assembly, but the mechanism of their synergy is co

37 or EB1 in negatively regulating APC-mediated actin assembly.

38 ntially regulating the small-GTPase RhoA and actin-associated protein Cortactin.

39 These areas differ in composition of actin-associated proteins and of phosphoinositides in th

40 trusion through directed polymerization of F-actin at the front.

41 ifting azimuthally between three states on F-actin (B-, C-, and M-states) in response to calcium bind

42 of a pharmacological treatment that thins F-actin bands, depletes E-cadherin, and stimulates prolife

43 We propose that this actin-based impaired relaxation is central to NEM6 patho

44 vealed that OY phytoplasmas spread along the actin-based muscle fibers of visceral muscles and accumu

45 Here, we study actin-based positioning mechanisms in artificial cells w

46 IM domain of these proteins disrupt tensed F-actin binding in vitro and cytoskeletal localization in

47 Reducing actin binding of L253P is thus a potential therapeutic a

48 t force transfer required talin's C-terminal actin binding site, ABS3, but not vinculin.

49 evidence for the critical role of the Tarp F-actin-binding domains in host cell invasion and for the

50 ty, reducing conformational flexibility of F-actin-binding domains via interdomain cross-talk and con

51 e-binding regions of myosin assures a proper actin-binding interface and active site have formed befo

52 the potential of our assay for detection of actin-binding modulators.

53 ind actin monomers directly, formins use the actin-binding protein profilin to dynamically load actin

54 Actin's interactions with myosin and other actin-binding proteins are essential for cellular viabil

55 Targeting the actin-binding proteins LIMK1 and LIMK2 significantly dim

56 Filaments are regulated by actin-binding proteins, but the nucleotide state of acti

57 zation and the interaction between actin and actin-binding proteins.

58 heads that increase the surface area of the actin-binding regions promoting myosin interaction with

59 myosin that increase the surface area of the actin-binding regions, promoting myosin interaction with

60 piece with functional assays to identify the actin-binding residues in FL villin that regulate its fi

61 In the proposed model, the N-terminal actin-binding site of leiomodin can act as a "swinging g

62 er, our study uncovers critical roles of the actin bundler T-Plastin to promote protrusions and migra

63 alpha-Actinins are major F-actin bundlers that are inhibited by Ca(2+) in nonmuscle

64 In scales, actin bundles are required for width formation.

65 s-linking, which enables the generation of F-actin bundles required for the sustained stabilization o

66 They contain actin bundles that dictate their cellular morphology.

67 ain cross-talk and consequently inhibiting F-actin bundling.

68 in-regulatory activities, but their distinct actin-bundling activities suggest that they also have di

69 ings could have wider implications for other actin-bundling proteins that contain a villin-type headp

70 Despite that, the actin-bundling site in the full-length (FL) villin prote

71 ial for the assembly of branched filamentous actin, but its role in physiology and development is sur

72 ibers from the newly attached cells into the actin cable and defusion from the previously lined cells

73 Prominent actin cables, spanning several cells, are abundant both

74 t in animals, as in yeast and plants, myosin/actin can drive long-range transport.

75 CAPZA2 encodes a subunit of an F-actin-capping protein complex (CapZ).

76 of isolated, bound cofilin molecules and an actin-cofilactin boundary indicate that cofilin-induced

77 three fibrotic markers: alpha-smooth muscle actin, collagen 1, and fibronectin.

78 Exon 17b peptides also promote fodrin-actin complex formation.

79 lowing binding, FH1 domains deliver profilin-actin complexes to filament ends.

80 actin boundary indicate that cofilin-induced actin conformational changes are local and limited to su

81 thdrawal involves NKCC1 transporters and the actin-controlling protein cofilin but does not depend on

82 Our results therefore indicate that actin cortex compression or dilation is possible in resp

83 se their plasma membrane from the underlying actin cortex when transitioning to a primed state.

84 Here, using actin cosedimentation, polymerization, and depolymerizat

85 We apply our approach to the actin cross-linker alpha-actinin-4 and show that the cro

86 While the role of actin cross-linking in controlling actin network mechani

87 ts these functions through SEPT9-dependent F-actin cross-linking, which enables the generation of F-a

88 luate real-time mechanical adaptation of the actin cytoskeletal network.

89 raction force (-40.1%) were lowered and VSMC actin cytoskeletal orientation was reduced (-24.5%) foll

90 The actin cytoskeletal regulator Wiskott Aldrich syndrome pr

91 es in motility suggest that FASN can mediate actin cytoskeletal remodelling; a process known to be do

92 we establish a link between the state of the actin cytoskeleton and the expression of pancreatic tran

93 was a KEAP1-binding protein that maintained actin cytoskeleton architecture and helped KEAP1 to sequ

94 d by xDC, cellular components other than the actin cytoskeleton dominate the response.

95 ics, in this work, we probed the role of the actin cytoskeleton in the dynamics, ligand binding, and

96 The actin cytoskeleton is a dynamic array of filaments that

97 The dynamic rearrangement of the actin cytoskeleton is an essential component of many mec

98 n of patient-derived GBM cells by modulating actin cytoskeleton pathway.

99 ies show the critical role [Ca(2+) ] and the actin cytoskeleton play in podocyte homeostasis.

100 The actin cytoskeleton plays a variety of roles in eukaryoti

101 Oligodendrocyte myelination depends on actin cytoskeleton rearrangement.

102 Previous studies examined long-term actin cytoskeleton responses to auxin, but plants respon

103 ile cells rely on both signaling modules and actin cytoskeleton to break symmetry and achieve a stabl

104 r photopharmacology targeting the ubiquitous actin cytoskeleton with precision control in the microme

105 pend on the organization and dynamics of the actin cytoskeleton, and the small, monomeric GTPases Rac

106 mon set of components: small GTPases and the actin cytoskeleton, which implies that the mechanisms do

107 he organization and dynamics of the cortical actin cytoskeleton.

108 pendent on an intact microtubule network and actin cytoskeleton.

109 ys that involve microtubule networks and the actin cytoskeleton.

110 ing between the extracellular matrix and the actin cytoskeleton.

111 we investigated the mechanism of coordinated actin delivery from the multiple polyproline tracts in f

112 otility are flagellar-dependent swimming and actin-dependent cell migration, both of which are used b

113 red a novel role for Par3 in controlling the actin-dependent forces acting on the nuclear envelope to

114 efficacy of APTi with two gene families, the actin-dependent motor, myosin XI (a,b), and the putative

115 SMARCD2 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily D, mem

116 Cadherin-mediated cell-cell adhesion is actin-dependent, but the precise role of actin in mainta

117 We found that beta-actin depletion affects induction of several adipogenic

118 ion and thereby inactivation of Cofilin1, an actin-depolymerizing protein, in ATG7-depleted cells.

119 mability increase upon latrunculin B-induced actin disassembly was detected only with cDC and sDC, wh

120 MA3F-mediated retention is associated with F-actin disassembly.

121 Here, we address the mechanism of F-actin-driven NE rupture by correlated live-cell, super-r

122 cups are organized into a ring or ruffle of actin-driven protrusion encircling a non-protrusive inte

123 d Trio have emerged as central regulators of actin dynamics at the synapse.

124 Altered protein synthesis and actin dynamics can lead to an abnormal neuronal morpholo

125 has a noncanonical role directly regulating actin dynamics.

126 likely cause of monogenic human SRNS due to actin dysregulation in podocytes.

127 tation-induced bolstering of the B-state Tpm-actin electrostatic contacts and an increased Tpm tropon

128 gamma-neurons, we focus here on the role of actin elongation factors as potential regulators of deve

129 and an increase in smooth muscle cell alpha-actin expression compared to untreated mice.

130 n cholangiocytes reduced alpha-smooth muscle actin expression in LX-2 cells treated with cholangiocyt

131 Study of filamentous-actin (F-actin) subsequently showed that SEMA3F-mediated

132 erm cells reveals defects in the filamentous actin (F-actin)-scaffolded acroplaxome during spermatid

133 omplex-mediated cell-autonomous control of F-actin fiber orientation relies on the preceding BM fibri

134 t switching process then occurs by fusion of actin fibers from the newly attached cells into the acti

135 el for the complex structure of CPEB3 and an actin filament (F-actin).

136 tips; they drive retrograde extension of an actin filament array that specifies anterograde microtub

137 example, modulate cell shape by accelerating actin filament assembly locally and slowing filament cap

138 of the tropomyosin cable that fits onto the actin filament between the tip of the myosin head and a

139 Coronin and Aip1 promote cofilin-mediated actin filament disassembly, but the mechanism is somewha

140 Here we show that branched actin filament networks, the main pushing machinery in c

141 The actin filament nucleator Arp2/3 complex is activated at

142 ation is required for CAP1 functions in both actin filament turnover and adhesion, and the novel mech

143 ip1 and attached to the end of the nucleated actin filament.

144 In vivo, colocalization of actin filaments and divalent ions are suppressed, and ce

145 We find that SMTNL2 binds to actin filaments and is required to slow down the turnove

146 ents showed that direct interactions between actin filaments and lipid bilayers are possible and that

147 py, making it difficult to determine whether actin filaments are directly associated with specific me

148 acts MICAL1, an enzyme known to depolymerize actin filaments by direct oxidation.

149 Arp2/3-nucleated actin filaments drive crawling motility and phagocytosis

150 In striated muscles, Tmods prevent actin filaments from overgrowing, whereas in non-muscle

151 d crosslinks nonpolymerizing MT plus ends to actin filaments in axonal GCs, preventing MT depolymeriz

152 bind barbed ends and retain pointed ends of actin filaments near beads and we identified Spire's bar

153 A model based on polymerizing actin filaments pushing against mitochondria, thus gener

154 Leaks are prevented by contractile actin filaments surrounding the diapedesis pore, keeping

155 rity in emerin, and thereby controls nuclear actin filaments that spatially segregate viral DNA from

156 hat neither talin nor vinculin alone recruit actin filaments to the membrane.

157 Cofilin binds actin filaments with positive cooperativity, forming clu

158 led actin filaments, whereas CLIK-1 bound to actin filaments without bundling them and antagonized UN

159 Without MYO7B or actin filaments, many clathrin-coated pits fail to be se

160 ied to fluorescent labels attached to single actin filaments, provides precisions within tens of nano

161 or cytoskeletal components, microtubules and actin filaments, together with a microtubule motor, kine

162 In vitro, UNC-87 bundled actin filaments, whereas CLIK-1 bound to actin filaments

163 tor that promotes polymerization of branched actin filaments.

164 which requires forces generated by MYO7B and actin filaments.

165 transport, initiated by nearby elongation of actin filaments.

166 cetylmimetics to map the relevant lysines on actin for INF2 regulation, focusing on K50, K61, and K32

167 seen when the incoming subunit was in the G-actin form.

168 ated with tissue remodeling, such as COL8A1, actin gamma-2 (ACTG2), and tetraspanin 12 (TSPAN12).

169 etween MCF10A and HL60 cells, the underlying actin guidance by nanotopography is similar in both cell

170 tal muscle actin in 1981, the pyrene-labeled actin has become the most widely employed tool to measur

171 molecular motors to transport the bacterial actin homolog MreB and the Rod PG synthesis complexes aw

172 mide was first used to label skeletal muscle actin in 1981, the pyrene-labeled actin has become the m

173 f macropinocytic cups and associate with the actin in actin waves. In contrast, Myo1D, E, and F are e

174 is actin-dependent, but the precise role of actin in maintaining cell-cell adhesion is not fully und

175 d dATP, myosin heads were extended closer to actin in relaxed muscle and myosin heads return to an or

176 d dATP, myosin heads were extended closer to actin in resting muscle.

177 es the intrinsic, stochastic fluctuations of actin in the growth cone to produce axon growth and guid

178 that pax2a(-/-) embryos fail to accumulate F-actin in the OF prior to basement membrane (BM) degradat

179 ubule-associated Pavarotti binds directly to actin in vitro and in vivo and has a noncanonical role d

180 creased binding and bundling activity with F-actin in vitro.

181 In U2OS cells, K50Q- and K61Q-actin inhibit INF2-mediated actin polymerization when ex

182 further contributed by biasing the remodeler-actin interaction toward nucleosomes with the non-canoni

183 By coupling the stress-sensitive cofilin-actin interaction with the light-responsive Cry2-CIB blu

184 inding proteins, but the nucleotide state of actin is also an important factor.

185 cally enriched in active protrusions where F-actin is devoid of non-muscle myosin II activity.

186 Because actin is more highly conserved than myosin and most othe

187 More recently, acetylation of actin itself was revealed to regulate cytoplasmic actin

188 lum (ER), mitochondria, acidic organelles, F-actin, keratin, and soluble fluorescein.

189 Consistently, in MsrB2-depleted cells, F-actin levels are decreased in ICBs, and dividing cells w

190 observations, knocking down EB1 increases F-actin levels in cells, and this can be rescued by disrup

191 The MreB actin-like cytoskeleton assembles into dynamic polymers

192 ith the magnetoskeleton-related MamY and the actin-like MamK via distinct motifs, and with the cell s

193 ament and has a conformation distinct from G-actin, meaning that incoming monomers would need to unde

194 experiments, we show that local depletion of actin-membrane links is needed for protrusion initiation

195 Actin-membrane release plays a similar role in protrusio

196 rtex is typically defined as a thin layer of actin meshwork that uniformly underlies the plasma membr

197 rate that MsrB2 selectively reduces oxidized actin monomers and thereby counteracts MICAL1, an enzyme

198 Whereas many of these proteins bind actin monomers directly, formins use the actin-binding p

199 he combination of all three factors produces actin monomers faster than any two factors alone.

200 binding protein profilin to dynamically load actin monomers onto their flexible Formin Homology 1 (FH

201 n to previously proposed local conversion of actin monomers to polymers, we demonstrate a surprising

202 reening to isolate antibodies that alter the actin morphology of filopodia-like structures (FLS) in v

203 e report an unexpected role for the atypical actin motor Myo6 in creating primary branch structure by

204 with a microtubule motor, kinesin-1, and an actin motor, myosin-V, are essential for osk mRNA poster

205 that ZBP1 and PAT1 co-locate along with beta-actin mRNA in actively transported granules in living ne

206 The aberrant beta-actin mRNA localization resulted in abnormal dendritic p

207 critical role for PAT1 in BDNF-induced beta-actin mRNA transport during postnatal development and re

208 ng is mediated, we used fluorescently tagged actin, mutant analyses, Ca(2+) imaging and controlled Ca

209 of actin and tropomyosin showed weakening of actin-mutant tropomyosin binding.

210 ractile actomyosin ring (AMR), composed of F-actin, myosin II, and other actin and myosin II regulato

211 pared to other cytoskeleton proteins such as actin, myosin, and tubulin.

212 (2020) describe a nuclear actin-myosin-based pathway driving the movement of activ

213 ablish the modus operandi for NAA80-mediated actin N-terminal acetylation, a modification with a majo

214 as a stable interactor and regulator of the actin N-terminal acetyltransferase NAA80, and establish

215 e role of actin cross-linking in controlling actin network mechanics is well-characterized in purifie

216 d to the dynamics of the underlying cortical actin network, as predicted by the dynamic picket-fence

217 oteins to connect the plasma membrane to the actin network.

218 ggers N-WASP-mediated assembly of a branched actin network.

219 which collective cell migration, large-scale actin-network fusion, and purse-string contraction orche

220 Here, we establish a novel role for actin networks in prion maintenance.

221 hizosaccharomyces pombe to assemble branched actin networks that drive endocytosis.

222 mechanics is well-characterized in purified actin networks, its mechanical role in the cytoplasm of

223 We show that transmembrane actin nuclear (TAN) lines are induced by stretch stimula

224 skott-Aldrich syndrome protein(N-Wasp) is an actin nucleation factor that promotes polymerization of

225 is can be rescued by disrupting APC-mediated actin nucleation.

226 ingly, ccb also interacts with actin and the actin nucleator spire The data revealed that this intera

227 The actin nucleators Spire and Cappuccino synergize to promo

228 n actomyosin network mainly generated by two actin nucleators: the Arp2/3 complex and the formin mDia

229 postsynaptic compartment, interactions with actin or its associated proteins are also critical for t

230 nce microscopy suggested that Amot's role in actin organization and dynamics also contributes to prom

231 Cell length predicted actin organization and dynamics in control roots; short-

232 nts dissect the nature of that regulation of actin organization and how it controls the spatial local

233 through the modulation of Ca(2+) signaling, actin organization, vesicle trafficking and cell wall de

234 ase inhibition caused disruption of cellular actin organization.

235 evisiae based on the discovery that cortical actin patches, which cluster near exocytic sites, are CM

236 ed to the apical membrane and affects apical actin placement and RAB-8-mediated vesicular transport.

237 Ena/VASP-family actin polymerases, for example, modulate cell shape by a

238 es pyroptosis in IECs in a Tir-dependent but actin polymerisation-independent manner, which was enhan

239 ring formation, dependent on ARP2/3 branched actin polymerisation.

240 atelets were pretreated with an inhibitor of actin polymerization (cytochalasin D [CytoD]).

241 g mechanism for cell protrusion, upregulated actin polymerization alone does not initiate protrusions

242 In summary, Rac activation leads to actin polymerization and recruitment of Myo9b, which loc

243 ely employed tool to measure the kinetics of actin polymerization and the interaction between actin a

244 Despite the well-established role of actin polymerization as a driving mechanism for cell pro

245 well-understood phenomenon that is based on actin polymerization at a cell's front edge and anchorin

246 ncing demonstrated that different degrees of actin polymerization biased cells toward various endoder

247 itself was revealed to regulate cytoplasmic actin polymerization through the formin INF2, with downs

248 , K50Q- and K61Q-actin inhibit INF2-mediated actin polymerization when expressed at low levels.

249 regulator, by pharmacological inhibition of actin polymerization, and by the expression of PCARE har

250 an act as a "swinging gate" allowing limited actin polymerization, thus making leiomodin a leaky poin

251 ed the stability of Pfn1 mRNA and influenced actin polymerization.

252 firmed using specific inhibitors of PI3K and actin polymerization.

253 tatively with Latrunculin A, an inhibitor of actin polymerization.

254 mplexes that activate pathways that catalyse actin polymerization.

255 in mouse oocytes results from a gradient of actin-positive vesicle activity and is essential for dev

256 ndidates, we characterized lysine 112 of the actin regulator cofilin as a novel neddylation event.

257 hat cause shorter FLS interact with SNX9, an actin regulator that binds phosphoinositides during endo

258 ring RNA (siRNA)-based down-regulation of an actin regulator, by pharmacological inhibition of actin

259 Tfap2c and Tead4 induce expression of actin regulators that control the recruitment of apical

260 vulation are likely mediated by their common actin-regulatory activities, but their distinct actin-bu

261 Further, the variants impair DAAM2-dependent actin remodeling processes: wild-type DAAM2 cDNA, but no

262 o increased H(2)O(2) and Ca(2+) levels and F-actin reorganization, but the mechanism of, and connecti

263 migrations are dependent on microtubules and actin, respectively, and the polarity crescent is the un

264 ite-directed mutagenesis of both cofilin and actin revealed residues critical for sustaining or abrog

265 intra-axonal calcium flux is accompanied by actin-Rho dependent growth of calcium rich axonal sphero

266 nal GCs, preventing MT depolymerization in F-actin-rich areas.

267 cells break tissue barriers by use of small actin-rich membrane protrusions called invadopodia.

268 Filopodia are finger-like actin-rich protrusions that extend from the cell surface

269 nding protein EB1/EBP-2 around the wound and actin ring formation, dependent on ARP2/3 branched actin

270 onto the gap front at which a pluricellular actin ring is already assembled.

271 An actin-ring segment switching process then occurs by fusi

272 membrane periodic skeleton (MPS) composed of actin rings interconnected by spectrin.

273 ibrils, reactive oxygen species, and cofilin-actin rods, present numerous challenges in the developme

274 Actin's interactions with myosin and other actin-binding

275 s in neurodegeneration and for investigating actin's interactions with other proteins during cellular

276 reveals defects in the filamentous actin (F-actin)-scaffolded acroplaxome during spermatid elongatio

277 d Cytoskeleton (LINC) complexes aligned with actin SFs.

278 Incorporation of K328Q actin significantly enhanced Ca(2+) sensitivity of RTF a

279 using a theoretical model, we argue that the actin-spectrin skeleton acts as an axonal tension buffer

280 wnregulation attenuated P aeruginosa-induced actin stress fiber formation and prevented paracellular

281 dynamic shortening of myosin IIA-associated actin stress fibers to drive rapid fibronectin fibrillog

282 a unique binding mode that does not perturb actin structure.

283 The small and transient actin structures regulating organelle dynamics are chall

284 f self-organizing into dynamic, micron-scale actin structures with features similar to cables in livi

285 Study of filamentous-actin (F-actin) subsequently showed that SEMA3F-mediated retentio

286 in head and a cleft on the innermost edge of actin subunits.

287 found to reduce Lifeact cosedimentation with actin, thus establishing the potential of our assay for

288 cargos for transport or engaging peripheral actin to stabilize MTs, suggesting several family member

289 ink intermediate filaments (IFs) rather than actin to the plasma membrane through protein complexes c

290 e motor protein myosin-Va works with dynamic actin tracks to drive long-range organelle dispersion in

291 mployed to identify troponin interactions on actin-tropomyosin because high-resolution experimentally

292 myofibrils, in non-muscle cells, Tmods bind actin-tropomyosin filaments to protect them from depolym

293 2e, 2f-g, 4a, 4j, 5a and 6b, unmatched beta-actin was inadvertently used as loading control for the

294 Formin ForB favors the actin wave and ForG the inner territory, whereas ForA, F

295 ontrast, Myo1D, E, and F are enclosed by the actin wave.

296 Although the speed and morphology of actin waves differ between MCF10A and HL60 cells, the un

297 nocytic cups and associate with the actin in actin waves. In contrast, Myo1D, E, and F are enclosed b

298 Since SP stabilizes F-actin, we speculated that the presence of SP within larg

299 d over potential "target" binding sites on F-actin where the corresponding interaction energetics of

300 ng regions promoting myosin interaction with actin, which could explain the observed delays in the on