ライフサイエンスコーパス: demethylation

1 ghts into how TET and TDG mediate active DNA demethylation.

2 e Treg phenotype characterized by FOXP3 TSDR demethylation.

3 ination does not contribute substantially to demethylation.

4 basic product dissociation during active DNA demethylation.

5 sion repair (BER) in the framework of active demethylation.

6 methylcytosine (5hmC), which can lead to DNA demethylation.

7 replication independent processes of active demethylation.

8 st-order rate potentials for methylation and demethylation.

9 d of care, mesna or nicotinamide-induced DNA demethylation.

10 ion (TET) family of dioxygenases can lead to demethylation.

11 ing the female pronucleus from TET3-mediated demethylation.

12 ay a role in gene expression mediated by DNA demethylation.

13 lcytosine (5hmC), are essential for cytosine demethylation.

14 DNA methylation and ROS1-mediated active DNA demethylation.

15 al roles in DNA base excision repair and DNA demethylation.

16 ng at CGIs, is correlated with TET1-mediated demethylation.

17 on is partly maintained by TET2-mediated DNA demethylation.

18 genases that are involved in DNA and histone demethylation.

19 ndritic-cell-specific or macrophage-specific demethylation.

20 en peroxide in the nucleus as a byproduct of demethylation.

21 mC, but also initiates active or passive DNA demethylation.

22 idized methylcytosines, intermediates in DNA demethylation.

23 -regulating Tet1 and Tet2, which promote DNA demethylation.

24 ion (TET) family members regulate active DNA demethylation.

25 DNA glycosylase ROS1, which facilitates DNA demethylation.

26 lase-1 (LSD1) has been shown to promote H3K9 demethylation.

27 The mammalian TET enzymes catalyze DNA demethylation.

28 onji C domain-containing protein 6) to G3BP1 demethylation.

29 stream of the JmjC domain do not disrupt UTX demethylation.

30 central role of BER in mediating active DNA demethylation, a multistep process that erases the epige

31 DNA demethylation, a process involving DNA repair, is critic

32 MeHg exported from upstream wetlands due to demethylation, absorption, deposition, and degradation b

33 intained equilibrium between methylation and demethylation activities is required to ensure long-term

34 The demethylation activity of atALKBH9B affected the infecti

35 ry (Hg) methylation and methylmercury (MMHg) demethylation activity of periphyton biofilms from the i

36 namic connection between FTO RNA binding and demethylation activity that influences several mRNA proc

37 siRNA diminished LSD1 protein stability and demethylation activity.

38 This lack of demethylation affects the expression of nearby B-cell li

39 Treatment with 5-aza-2'-deoxycytidine, a demethylation agent, and knockdown of DNA methyltransfer

40 In late gestation, genome-wide H3K27 demethylation allowed for target gene upregulation, deci

41 l demethylation of A253 cells and found that demethylation alone induced robust AQP1 expression.

42 n by coordinating efficient TDG-mediated DNA demethylation along with active transcription during som

43 PodA-dependent pyocyanin demethylation also restricts established biofilm aggrega

44 Structure-activity analysis revealed that N-demethylation alters the interaction of PK11195 with the

45 including a JmjC domain that catalyzes H3K36 demethylation and a CxxC zinc-finger that recognizes CpG

46 osteoblast differentiation as it impairs DNA demethylation and alters the recruitment of histone meth

47 ent utilization of LigM as a tool for aryl O-demethylation and as a component of synthetic biology ef

48 The link between inhibition of DNA demethylation and changes in expression is strong in som

49 ve epigenome resetting, including global DNA demethylation and chromatin reorganization.

50 We also provide evidence that promoter demethylation and close non-coding RNAs (namely, CT-ncRN

51 1-dependent enhancers and mediates local DNA demethylation and concomitant histone 3 lysine 4 methyla

52 ropionic acid derivatives via hydrogenation, demethylation and dehydroxylation to give metabolites th

53 ase TET proteins play important roles in DNA demethylation and development.

54 pposition to 5mCG, resulting in "functional" demethylation and diminished MeCP2 binding, thus facilit

55 t is a dynamic balance between strong global demethylation and drastic focused remethylation.

56 -site, whereas RelA knockdown suppresses CpG demethylation and EpCAM expression.

57 e acquisition of the dendritic-cell-specific demethylation and expression signature, following STAT6

58 dCas9-mediated locus-specific demethylation and global inactivation of DNMT3B in TKO h

59 Our results indicate that DNA demethylation and histone acetylation are coordinated to

60 asferase EZH2, TET2 a key factor in cytosine demethylation and inactive DNMT3L, shown by knockdown as

61 and functionally, and provides insight into demethylation and its reaction requirements.

62 of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type

63 tal period, we demonstrated that both global demethylation and remethylation in early development cor

64 periments from "IDH mutation impairs histone demethylation and results in a block to cell differentia

65 ntage of its recently discovered role in DNA demethylation and selective recognition and repair of 5-

66 ut ascorbate (vitamin C), which promotes DNA demethylation and subsequently changes the sensitivity t

67 rs of Notch target genes, leading to H3K4me2 demethylation and to transcriptional repression.

68 thyltransferase Dnmt1 induces widespread DNA demethylation and transcriptional activation of ERVs, in

69 iting Wnt signaling, partly through promoter demethylation and transcriptional activation of the Wnt

70 direct connections between TET-mediated DNA demethylation and transcriptional output are difficult t

71 rehensive transcriptome-wide analysis of RNA demethylation and uncover FTO as a potent regulator of n

72 ogression, in part, through the specific DNA demethylation and upregulation of epidermal growth facto

73 tically, peripheral nerve injury induces DNA demethylation and upregulation of multiple regeneration-

74 fector proteins, induce their methylation or demethylation, and alter their conformation.

75 5hmC), providing an active mechanism for DNA demethylation, and it may also provide its own regulator

76 ins expression of KLF2 and IRF4 through H3K9 demethylation, and knockdown of KLF2 triggers apoptosis.

77 y and catalytic competency of the engineered demethylation apparatus in biochemical assays.

78 Thus, tissue-specific DNA demethylation appears to be necessary for proper somatic

79 lly, we show that the main drivers of global demethylation are neither active mechanisms (Aicda, Tdg,

80 umor type, both CGI methylation and backbone demethylation are often associated with clinical, epidem

81 DNA methylation and demethylation are opposing processes that when in balanc

82 A tandem demethylation-aryl borylation strategy was developed to

83 vidence of trans-chromosomal methylation and demethylation as well as other possibilities.

84 Lysine demethylation, as catalysed by two families of lysine de

85 Modulation of histone and DNA demethylation, as well as HIF-1alpha stability, mediate

86 Demethylation associates with increased gene expression,

87 e in the level of 5hmC with accompanying DNA demethylation at a subset of CGIs.

88 lecular rheostat selectively regulating H3K9 demethylation at cell cycle gene loci, thereby represent

89 ic activity of LSD1 is essential for H3K9me2 demethylation at cell cycle gene loci.

90 We found that ThymoD transcription promoted demethylation at CTCF bound sites and activated cohesin-

91 , DNA remethylation at the IL-4 promoter and demethylation at IFN-gamma and Foxp3 promoters.

92 LID development led to significant demethylation at many important regulatory areas of aber

93 g age-related methylation in CpG islands and demethylation at shore/shelf and open sea.

94 [i.e., forced swimming (FS)] results in DNA demethylation at specific CpG (5'-cytosine-phosphate-gua

95 Conversely, demethylation at the HLA-E CGI restores HLA-E protein ex

96 entiation in part by countering LSD1 H3K4me1 demethylation at the RUNX2 enhancer.

97 cated as intermediates on the path to active demethylation, but recent reports have suggested that th

98 wn of JMJD6 repressed SG formation and G3BP1 demethylation, but SG formation and G3BP1 demethylation

99 TETs drive LINE-1 demethylation, but surprisingly, LINE-1s are kept repres

100 t TET2, a cellular enzyme that initiates DNA demethylation by converting 5-methylcytosine (5mC) into

101 f TET2, a cellular enzyme that initiates DNA demethylation by converting 5-methylcytosine (5mC) into

102 ect is likely the result of both passive DNA demethylation by DNMTi and active conversion of 5-methyl

103 ution of the TTD to the catalysis of H3K9me3 demethylation by KDM4C and demonstrated that TTD-mediate

104 Here, we characterize aryl O-demethylation by LigM and report its 1.81-A crystal stru

105 argeting protein, UHRF1, can augment the DNA demethylation capacities of existing DNA methylation inh

106 thylation reduced reporter activity, whereas demethylation caused biallelic CD177 expression.

107 exogenous source of alphaKG restored the DNA demethylation cycle by promoting TDG function, TET1 nucl

108 fications to cytosine in the proposed active demethylation cycle is demonstrated at the single-molecu

109 Restoring the epimetabolic control of DNA demethylation cycle promises beneficial effects on cells

110 The observed sequential methylation/demethylation cycle suggests an important role of DNA me

111 d by enzymatic reactions including oxidative demethylation/deamination and myeloperoxidation, it is u

112 Rates of demethylation did not differ between CCs and REFs.

113 of all SALL4 exons increased, suggesting CpG demethylation downstream from SALL4 TSS influences SALL4

114 To understand how CpG demethylation downstream of SALL4 TSS regulates SALL4 tr

115 Demethylation during generation of volatile hydrides (HG

116 chromatin formation pathways, whereas global demethylation during germination occurs in a passive man

117 me3-binding by KDM4B directs localized H3K36 demethylation during meiosis and spermatogenesis.

118 cribing the regional contribution of 5hmC to demethylation dynamics.

119 LigM-catalyzed demethylation enables further modification and ring open

120 at comprehensively describes DNA methylation/demethylation events in two neuronal lineages, with a to

121 oxidized 5mC bases indicative of active DNA demethylation events.

122 largely prevents lineage-specific programmed demethylation events.

123 ing the importance of this region and of its demethylation for fut7 transcription in T cells.

124 T cell-specific demethylation region (TSDR) demethylation, FOXP3 expression, and suppression were an

125 d streptozotocin mice eliciting, in HFD, DNA demethylation, glucose uptake, and insulin response.

126 d hypoxia-inducible factor alpha (HIF1alpha) demethylation has recently been proposed, the effect of

127 Therefore, bypassing stage-specific DNA demethylation has significant consequences for progenito

128 epigenetic mark produced through active DNA demethylation, has not been previously investigated in F

129 We sought to investigate the role of DNA demethylation in activating inflammasome genes during ma

130 ursor protein cleaving enzyme 1 (bace-1) DNA demethylation in AD-vulnerable brain regions.

131 g et al. (2017) reveal a role for active DNA demethylation in allowing axon regeneration to occur in

132 (alphaKG) in the epimetabolic control of DNA demethylation in CMSCs.

133 recapitulated the process of genome-wide DNA demethylation in embryonic PGCs, including significant d

134 ce of events leading to direct gene-specific demethylation in innate immune cell differentiation.

135 overall methylation in CpG island (CGI) and demethylation in intergenic regions, defined as 'backbon

136 Pharmacological inhibition of H3K27 demethylation in late gestation not only prevented term

137 mportantly, the maintenance of PD-1 promoter demethylation in memory CD8 T cells was coupled with imp

138 nal significance of cytosine methylation and demethylation in mouse embryogenesis remains to be fully

139 del the contribution of 5hmC to processes of demethylation in mouse ESCs.

140 establish the molecular mechanism for global demethylation in naive ESCs, which has key parallels wit

141 simple rules that govern DNA methylation and demethylation in neuronal development in vivo.

142 nal development, the role of DNA methylation/demethylation in neuronal lineage and subtype specificat

143 odulates Lefty-Nodal signalling by promoting demethylation in opposition to methylation by DNMT3A and

144 biological relevance of DNA methylation and demethylation in plant immunity against nonviral pathoge

145 , highlights an unexpected importance of Ddo demethylation in preventing neurodegenerative processes

146 E2 receptor 4 (PTGER4) is upregulated after demethylation in resistant cells.

147 accelerator of global and locus-specific DNA demethylation in somatic and pluripotent stem cells.

148 However, the requirement for active H3K27 demethylation in stem cell-mediated tissue regeneration

149 ible yet elusive role of DNA methylation and demethylation in systemic immune responses, transgenerat

150 Maternal obesity induces DNA demethylation in the promoter of zinc finger protein 423

151 nisms and critical functional players of DNA demethylation in this process remain largely unexplored.

152 of TET enzyme, which is responsible for DNA demethylation in UVB-exposed skin.

153 more, the biological functions of active DNA demethylation in various biological contexts have also b

154 hereby challenging the need for active H3K27 demethylation in vivo.

155 vealed a physiological role for active H3K27 demethylation in vivo.

156 T3 derepressed NR4A3 expression, by promoter demethylation, in AGS GC cells.

157 tumor suppressor p15(INK4B) through promoter demethylation; in turn, DNMT1 dysfunction impairs KIT ki

158 to the c-Myc gene enhancer and induced H3K9 demethylation, increasing AR-dependent transcription of

159 In ESCs with DNA demethylation induced by acute deletion of Dnmt1, we saw

160 We further establish that DNA demethylation induced by XPC expression in somatic cells

161 NAs are involved in an immediate response to demethylation-induced transposon activation, while the d

162 loped to map the genomic distribution of the demethylation intermediates 5-formylcysotine (5fC) and 5

163 domain prevents large SG assembly and rapid demethylation is a novel signal that regulates SG format

164 out of the Eed subunit of PRC2 indicate that demethylation is a rate-limiting step in the activation

165 cell activation and that JMJD3-driven H3K27 demethylation is critical for CD4 T cell function.

166 To assess if PD-1 promoter DNA demethylation is impacted by prolonged stimulation durin

167 lls (SCs) and demonstrated that active H3K27 demethylation is necessary for muscle regeneration.

168 Global demethylation is part of a conserved program of epigenet

169 Demethylation is TET2-dependent and is essential for acq

170 ctivation of naive and memory cells and that demethylation is the predominant change to H3K27me3 at t

171 licated in hydroxymethylation and active DNA demethylation, is a key regulator of EBV latency type DN

172 1(+) , encoding an enzyme that promotes H3K9 demethylation, is deleted.

173 model, which accurately predicts global DNA demethylation kinetics.

174 In CRC cell lines, we demonstrated that EREG demethylation led to its transcriptional upregulation, h

175 Emerging evidence suggests that active DNA demethylation machinery plays important epigenetic roles

176 has a strong impact on replication dependent demethylation, mainly by impairing methylation maintenan

177 as consistent with our previous finding that demethylation may cause regain of PRC2 in demethylated r

178 ng sequence, supporting that this active DNA demethylation mechanism functions during oncogenic trans

179 We also show that DDB2 regulates active DNA demethylation mediated by REPRESSOR OF SILENCING 1 (ROS1

180 d by decreased nucleosome enrichment and DNA demethylation mediated by SWI/SNF- and Tet1/Tet2-contain

181 gulation of EREG expression through promoter demethylation might be an important means of activating

182 providing chloride for post-rate-determining demethylation/neutralization of the resulting zwitterion

183 In PGCs, global and locus-specific DNA demethylation occur in sequential stages, with an initia

184 Demethylation occurred first at binding motifs for the t

185 RelA-dependent demethylation occurring upon HBx expression requires met

186 but the mechanism by which TDG-dependent DNA demethylation occurs in a rapid and site-specific manner

187 ts that quantitatively little methylation or demethylation occurs in cytoplasmic mRNA.

188 etion of TDG suggest TET/TDG-mediated active demethylation occurs preferentially at intron-exon bound

189 of antiangiogenic miR-221 by GATA2-dependent demethylation of a putative CpG island in the miR-221 pr

190 onstrate that fumarate inhibits Tet-mediated demethylation of a regulatory region of the antimetastat

191 second study, we performed global, chemical demethylation of A253 cells and found that demethylation

192 Hydrolysis and demethylation of arsenic glutathione complexes and arsen

193 The most potent inhibitors induced demethylation of CDKN2A promoter in colon carcinoma HCT1

194 We further demonstrate demethylation of cognate substrates in physiologically r

195 Demethylation of COL2 increases its expression, inducing

196 We conclude demethylation of CpGs located within OCT4 and STAT3 cis-

197 Demethylation of DNA abrogated the protective effect of

198 l hypomethylated state and site specific DNA demethylation of enhancer elements within the proximal p

199 Here we report widespread DNA demethylation of enhancers during the phylotypic period

200 ting in dissociation of CRTC2, LSD1-mediated demethylation of gene-activation histone marks H3K4-me2/

201 y in the molecular and Purkinje cell layers, demethylation of genome-wide repetitive LINE-1 elements,

202 B by the SAGA complex as well as restricting demethylation of H3 and increasing its acetylation.

203 Hence, the demethylation of H3K36 is linked to the pathogenesis of

204 Mechanistically, demethylation of H3K4me3 is required for ZMYND8-NuRD bin

205 D-mediated recognition of H3K4me3 stimulates demethylation of H3K9me3 in cis on peptide and mononucle

206 The interplay between methylation and demethylation of histone lysine residues is an essential

207 L-4; and, accordingly, were characterized by demethylation of IL4, IL13, IL5, GATA3, and RORC2, where

208 ion in embryonic PGCs, including significant demethylation of imprint control regions (ICRs) associat

209 samples were found to overexpress IGF2, via demethylation of its fetal promoter.

210 Demethylation of MA and DMA from rice occurs increasing

211 Pronounced demethylation of MAs(V), DMAs(V), and TMAs(V)O was found

212 amination was proposed to be involved in the demethylation of mC for epigenetic regulation.

213 acterial gene (arsI) responsible for aerobic demethylation of methylarsenite (MAs(III)).

214 enes identified as the bacterium active in O-demethylation of MTBE.

215 It mediates the demethylation of N(1)-methyladenosine (m(1)A) in tRNAs.

216 uals, little is known about when this stable demethylation of PD-1 promoter DNA is programmed during

217 Lysine demethylation of proteins such as histones is catalyzed

218 Specific DNA demethylation of regulatory sequences can result in upre

219 ed HCCs expressing increased SALL4 exhibited demethylation of specific CpG sites downstream of SALL4

220 development is accompanied by extensive DNA demethylation of specific sites that vary between cell t

221 Targeted demethylation of the BDNF promoter IV or the MyoD distal

222 ssion of Dpp4 in the liver is facilitated by demethylation of the Dpp4 gene early in life.

223 Monocytes showed an even more extensive demethylation of the FUT7 gene whereas hepatocytes, whic

224 This is achieved by rapid demethylation of the insulin and glucagon gene promoters

225 Dehydrogenation, epoxidation, and demethylation of the latter afforded 1.

226 Furthermore, demethylation of the paternal genome is much faster and

227 While demethylation of the PD-1 promoter DNA is observed in ex

228 model system, we found a correlation between demethylation of the promoter induced by the treatment,

229 The ALKBH1-catalyzed demethylation of the target tRNAs results in attenuated

230 Demethylation of these compounds is essential for downst

231 patitis C virus-related HCCs correlated with demethylation of these CpG sites.

232 Similarly, SALL4 re-expression and demethylation of these CpGs was observed in HBV replicat

233 HepG2 cells derived from human HCC exhibit demethylation of these NF-kappaB-flanking CpG sites, and

234 phenotype, abrogated the activation-induced demethylation of this region, which contains a cAMP resp

235 Specifically, ISL1 promotes the demethylation of tri-methylation of histone H3K27 (H3K27

236 oma-carcinoma transition was associated with demethylation of two key sites within its promoter, and

237 the VAV1 gene body that was correlated with demethylation of two promoter CpGs (CpG6772370/CpG677281

238 Demethylation of UCH-L1 promoter was associated with UCH

239 Our results demonstrate that incomplete demethylation on the SRY gene is the driving cause of XY

240 on and likely mediates dynamic site-specific demethylation outside of CGIs.

241 lved in cellular signalling activities while demethylations particularly linked to functions of the e

242 However, an active DNA demethylation pathway is initiated during late seed deve

243 oxidise DNA methylation as part of an active demethylation pathway.

244 n at unprecedented detail, quantifies active demethylation pathways and reveals 5hmC localization in

245 of TET-5hmC pathways and reveal critical DNA demethylation patterns.

246 ss where regulatory components mediating DNA demethylation play a leading role.

247 Here, we show that TET2-mediated DNA demethylation plays a primary role in the de novo establ

248 ular tumor suppressor involved in active DNA demethylation, plays a central role in regulating the DN

249 ure and biofilm structure on methylation and demethylation potentials were examined.

250 ion by replication dependent and independent demethylation processes has been suggested to be influen

251 of our work is that the neuronal methylation/demethylation program is predominantly developmental wit

252 eriod after repair, transcription-associated demethylation promoted by Base Excision Repair enzymes f

253 re also repaired by AlkB-catalyzed oxidative demethylation, providing a potential alternative mechani

254 Methylmercury demethylation rate constants (kd) were of similar magnit

255 ve (MW) kinetics of an industrially relevant demethylation reaction is presented.

256 iled to mediate the complete the cyclization/demethylation reaction sequence by itself.

257 e pyrazine ring via an unusual tautomerizing demethylation reaction.

258 It is shown that demethylation reduces the association of melittin with m

259 Regulatory T cell-specific demethylation region (TSDR) demethylation, FOXP3 express

260 We find that LSD1, via H3K4me1 demethylation, represses the master regulator of osteobl

261 ion (TET) family of dioxygenase-mediated DNA demethylation requires new methods to quantitatively map

262 3) and transposable elements are enriched at demethylation-resistant regions, while active chromatin

263 ylated ros1 mutant, which is affected in DNA demethylation, revealed that their opposite resistance p

264 (3) Methylation/demethylation, similar to transcription, are initially h

265 The extent of demethylation strongly depends on concentration of the a

266 omal methylation (TCM) and trans-chromosomal demethylation (TCdM).

267 Essential for DNA demethylation, TDG excises 5-formylcytosine and 5-carbox

268 atients with CAPS undergo more efficient DNA demethylation than those of healthy subjects.

269 TET enzymes catalyse DNA demethylation through 5-methylcytosine oxidation.

270 es are reported to have a role in active DNA demethylation through 5mC oxidation and DNA repair, amon

271 ence somatic gene expression and dynamic DNA demethylation to activate pluripotency gene transcriptio

272 sis factor-alpha activates RelA, propagating demethylation to nearby CpG sites, shown by sodium bisul

273 ng CpG sites, and HBV replication propagates demethylation to nearby CpG sites.

274 ic barrier that can be removed by active DNA demethylation to permit axon regeneration in the adult m

275 et1 and Jhd2 via modulating H3K4 methylation-demethylation together control chromatin dynamics during

276 addition, the supernatant of the cells after demethylation treatment displayed an enhanced ability of

277 Bisulphite pyrosequencing and demethylation treatment showed that NR4A3 was epigenetic

278 PTPRO reexpression by demethylation treatment using 5-azacytidine reduced the

279 ethods for the genomic mapping of active DNA demethylation using limited numbers of cells or single c

280 The ratio of methylation to demethylation varied between 0.3 and 1.5, suggesting tha

281 To understand mammalian active DNA demethylation, various methods have been developed to ma

282 s have also been proposed to function in DNA demethylation via deamination of either 5-methylcytosine

283 The mechanism is NaCl-induced DNA demethylation via the recruitment of the hydroxytransfer

284 SFN enhances active DNA demethylation viaTet1andTet2and promotes preosteoblast d

285 Foxp3 demethylation was associated with tolerance induction, i

286 Effector-loci demethylation was heritably preserved during IL-7- and I

287 ted expression of H19 lncRNA due to promoter demethylation was observed in cells isolated from metast

288 se 2 (TET2) and nuclear factor kappaB to DNA demethylation was tested by using chromatin immunoprecip

289 et1, a tumor suppressor involved in cytosine demethylation, we observed a similar loss of promoter co

290 To reproduce a rapid and extensive demethylation, we subjected mouse ES cells to chemically

291 P1 demethylation, but SG formation and G3BP1 demethylation were rescued with catalytically active but

292 ndent repair of DNA lesions arising from DNA demethylation, which prevents zygotes carrying unrepaire

293 and chromatin organization by way of histone demethylation, which provides a means to regulate the ac

294 19p gain and polycomb features, and backbone demethylation with chromosomal instability, NSD1 and TP5

295 muM, respectively, catalyzing sterol 14alpha-demethylation with respective turnover numbers of 1.7 mi

296 We observe KDM5A-dependent H3K4me3 demethylation within chromatin near DNA double-strand br

297 man CD4(+) effector memory T cells confirmed demethylation within FUT7 corresponding to high FUT7 exp

298 gene expression is paralleled by progressive demethylation within its putative promoter region.

299 In conclusion, we show that DNA demethylation within the fut7 gene controls selectin lig

300 ion of DMABN mainly proceeded (>72%) through demethylation yielding N-methyl-4-cyanoaniline and forma