ライフサイエンスコーパス: inclusion body

1 rom Escherichia coli after refolding it from inclusion bodies.

2 use of urea-denatured protein purified from inclusion bodies.

3 nd has a defect in the formation of Htt103QP inclusion bodies.

4 ylation is sufficient for translocation into inclusion bodies.

5 at are improved byl-DOPA, and development of inclusion bodies.

6 n based of crude hydrolyzed ILV-labeled OmpX inclusion bodies.

7 differential accumulation of electron-dense inclusion bodies.

8 cations and usually need to be refolded from inclusion bodies.

9 by immunohistochemistry or visualization of inclusion bodies.

10 are aggregation-prone and form intracellular inclusion bodies.

11 tration of partially misfolded proteins into inclusion bodies.

12 indispensable for the removal of TDP-43Delta inclusion bodies.

13 and familial encephalopathy with neuroserpin inclusion bodies.

14 olubilized, and are usually sequestered into inclusion bodies.

15 red into detergent-insoluble, Hsp42-positive inclusion bodies.

16 ressed in Escherichia coli and refolded from inclusion bodies.

17 the JEV E ectodomain refolded from bacterial inclusion bodies.

18 ted in a punctate pattern characteristic for inclusion bodies.

19 e: the deposition of the culprit proteins in inclusion bodies.

20 peats) after targeted photo-bleaching of the inclusion bodies.

21 ressed in Escherichia coli and refolded from inclusion bodies.

22 e ebolavirus polymerase L, which is found in inclusion bodies.

23 S) formed polar foci that were distinct from inclusion bodies.

24 d then purified and recovered from bacterial inclusion bodies.

25 a specific peptide, which blocks binding to inclusion bodies.

26 rotein than infected cells that did not form inclusion bodies.

27 with enhanced accumulation of ER-derived ATZ inclusion bodies.

28 lead to their aggregation and deposition in inclusion bodies.

29 y be predicted from their propensity to form inclusion bodies.

30 ily, are assumed to replicate in cytoplasmic inclusion bodies.

31 Expressed fusions formed inclusion bodies.

32 btained using refolded material from E. coli inclusion bodies.

33 ccessfully refolded from solubilized E. coli inclusion bodies.

34 se LRRK2 into more insoluble and homogeneous inclusion bodies.

35 modify cell shape but produced intracellular inclusion bodies.

36 teins involved the recovery of proteins from inclusion bodies, a process that is tedious and may lead

37 h light and electron microscopy (EM) levels, inclusion body accumulation was seen in satellite cells

38 Sso AcP aggregates in vivo to form bacterial inclusion bodies after expression in E. coli.

39 Polar MurG foci are distinct from inclusion body aggregates, and polar MurG can be remobil

40 Association of ATI mRNA with inclusion bodies allows multiple rounds of local transla

41 often tend to aggregate upon expression into inclusion bodies and are difficult to refold.

42 lar chaperones Hsp70 and Hsp40 colocalize to inclusion bodies and are neuroprotective in HD animal mo

43 form are quantitated using both protein from inclusion bodies and denatured recombinant protein from

44 he mutant protein accumulates in cytoplasmic inclusion bodies and does not reach the membrane.

45 f the protein (which is fused to TrpLE) into inclusion bodies and releasing the target protein by cya

46 -alpha7 is involved in the formation of EBOV inclusion bodies and replication.

47 (i.e., formation of very large intracellular inclusion bodies and slow degeneration over a period of

48 granules are distinct from cytoplasmic viral inclusion bodies and that the RNA binding protein HuR, n

49 In addition to inclusion bodies and the diffuse pool of monomers and ol

50 The cells fill with large inclusion bodies and the membrane becomes irregularly sh

51 frequently revealed eosinophilic inclusions (inclusion bodies) and rimmed vacuoles, but was non-speci

52 h alterations in pigmentation, heterogeneous inclusion bodies, and a lower PSI/PSII ratio than the WT

53 concentrated to the aggresome, a perinuclear inclusion body, and subsequently removed by autophagy.

54 Inclusion bodies are a characteristic feature of ebolavi

55 Although inclusion bodies are a prominent feature in MeV-infected

56 Ubiquitin-containing inclusion bodies are characteristic features of numerous

57 ntingtin in these mice demonstrated that the inclusion bodies are composed largely of a much smaller

58 ectron microscopic studies indicate that the inclusion bodies are consistent with aggregates of viral

59 ch as stress granules and processing bodies, inclusion bodies are exclusively present in infected cel

60 Live-cell imaging further showed that inclusion bodies are highly dynamic structures and that

61 nert aggregates of nucleocapsids, ebolavirus inclusion bodies are in fact complex and dynamic structu

62 t RNAs using click technology we showed that inclusion bodies are indeed the site of viral RNA synthe

63 of expression, Sso AcP is incorporated into inclusion bodies as a native-like protein, still exhibit

64 uses to understand the mechanisms regulating inclusion body assembly.

65 observed in connection with the cylindrical inclusion bodies at structurally modified PDs in cells c

66 ul, ambient conditions, creating non-amyloid inclusion bodies at the nuclear-vacuolar junction, and i

67 Here we report a rapid method for refolding inclusion-body-based, recombinant cell surface receptors

68 t viral RNA predominantly localized to viral inclusion bodies but a small percentage also interacted

69 ld be extracted, refolded, and purified from inclusion bodies, but when subjected to analytical gel f

70 s including aggresomes, stress granules, and inclusion bodies caused by huntingtin polyglutamine expa

71 fectious virions outside of the factories in inclusion bodies comprised of numerous copies of the 150

72 st expression levels and for the presence of inclusion bodies containing aggregated protein.

73 LGMD1D muscle has rimmed vacuoles and inclusion bodies containing DNAJB6, Z-disc proteins and

74 (htt) protein, resulting in accumulation of inclusion bodies containing fibrillar deposits of mutant

75 o deposition of cytoplasmic and intranuclear inclusion bodies containing htt.

76 We show that mammalian JUNQ inclusion bodies containing soluble misfolded proteins a

77 aracterized by the presence of intracellular inclusion bodies containing the mutant FTL polypeptide a

78 In RSV- or HMPV-infected cells, cytosolic inclusion bodies containing the nucleoprotein, phosphopr

79 blue staining of SGs demonstrated that these inclusion bodies corresponded to sulfatide accumulation.

80 Boid inclusion body disease (BIDB) is a fatal disease of boid

81 Inclusion body disease (IBD) is an infectious disease or

82 s to demonstrate that reptarenaviruses cause inclusion body disease (IBD), a serious transmissible di

83 uclear inclusions suggestive of intranuclear inclusion body disease (NIID).

84 nnulated tree boas (Corallus annulatus) with inclusion body disease and is implicated in the disease

85 arenavirus infection produces inclusions and inclusion body disease, although inclusions per se are n

86 The newly discovered boid inclusion body disease-associated arenaviruses (BIBDAV)

87 in stress granules, also localized to viral inclusion bodies during infection.

88 V) epidemic in 2009 in South Africa, measles inclusion body encephalitis (MIBE) was identified in sev

89 and lead to complications, including measles inclusion body encephalitis (MIBE).

90 the conformational properties of proteins in inclusion bodies exhibit many of the characteristics typ

91 ia, familial encephalopathy with neuroserpin inclusion bodies (FENIB), has been proposed, which may p

92 rmation of large cytoplasmic granules, named inclusion bodies, for genome replication and transcripti

93 ow a strong correlation between the level of inclusion body formation and aggregation propensity, thu

94 of ER protein overload in mutants that cause inclusion body formation and alpha1AT deficiency.

95 rimary cilia formation through p62-dependent inclusion body formation and blockage of Bardet-Biedl sy

96 ty is saturable, the rate-limiting steps for inclusion body formation and death can be traced to diff

97 ne complexes, increasing ATZ-BiP binding and inclusion body formation and reducing ATZ interactions w

98 acts with viral protein VP35 to control both inclusion body formation and RNA synthesis.

99 ApiCCT1(r) also delays the onset of inclusion body formation as visualized via live imaging.

100 sing this virus, we showed that the onset of inclusion body formation corresponds to the onset of vir

101 Of importance, the defect of inclusion body formation in dsk2 mutants can be rescued

102 Thus, an understanding of inclusion body formation is crucial for the discovery of

103 Though inclusion body formation is nuanced, it corresponds to a

104 re, we show that infection with MeV triggers inclusion body formation via liquid-liquid phase separat

105 Inclusion body formation was consistent with an actin-de

106 errant aggregation of misfolded proteins and inclusion body formation, a hallmark of neurodegenerativ

107 that the UBL domain of Dsk2 is critical for inclusion body formation.

108 s induced for a short time before noticeable inclusion body formation.

109 clearance of misfolded proteins by promoting inclusion body formation.

110 data suggest that the HSR does not mitigate inclusion body formation.

111 but that viral transcription occurs prior to inclusion body formation.

112 unds, but also to investigate the biology of inclusion body formation.

113 ivity in LRRK2-induced neuronal toxicity and inclusion body formation.

114 ve identified two domains of NP that control inclusion body formation.

115 ateral sclerosis (ALS), are characterized by inclusion bodies formed by polyubiquitinated and hyperph

116 However, when the inclusion body forms after a long Htt103QP induction, Ds

117 ay influence the formation of aggregates and inclusion bodies generated by mutant SOD1.

118 inuclear compartment consists of cytoplasmic inclusion bodies generated in response to the accumulati

119 athogenesis (11 weeks of age), whereas large inclusion bodies have not been observed in the brains of

120 degeneration (FTLD) with ubiquitin-positive inclusion bodies-have been linked to familial forms of b

121 fection induces the formation of cytoplasmic inclusion bodies (IB), comprised mainly of viral nucleop

122 mHtt) proteins, rendering them prone to form inclusion bodies (IB).

123 A5 and MAVS were observed within large viral inclusion bodies (IB).

124 ntingtin (htt) induces self-aggregation into inclusion bodies (IBs) and causes Huntington's disease (

125 Ebola virus (EBOV) inclusion bodies (IBs) are cytoplasmic sites of nucleoca

126 domain of NP, the central domain.IMPORTANCE Inclusion bodies (IBs) are cytoplasmic sites of RNA synt

127 Inclusion bodies (IBs) containing aggregated disease-ass

128 infected with HMPV revealed the formation of inclusion bodies (IBs) from early times postinfection.

129 tory syncytial virus (RSV) forms cytoplasmic inclusion bodies (IBs) that are thought to be sites of n

130 roteins within and at the perimeter of viral inclusion bodies (IBs), respectively.

131 s ectopically expressing mutant LRRK2 formed inclusion bodies (IBs), retracted neurites, accumulated

132 e cytoplasm, which are synonymous with viral inclusion bodies (IBs), the site for viral RNA replicati

133 03Q(Exon1)-EGFP from a diffuse ensemble into inclusion bodies (IBs), whereas the destabilizing osmoly

134 s (CaMV) is responsible for the formation of inclusion bodies (IBs), which are the sites for viral ge

135 ation of insoluble protein aggregates called inclusion bodies (IBs).

136 ine TDP-43 and with human recombinant TDP-43 inclusion bodies (IBs).

137 tected in viral replication factories termed inclusion bodies (IBs).

138 Intracytoplasmic inclusion bodies (ICI) have been identified in ciliated

139 These antibodies identify intracytoplasmic inclusion bodies in acute KD tissues.

140 THL treatment reduced tissue inclusion bodies in brain, and peripheral organs, but di

141 e concentration threshold at which HTT forms inclusion bodies in cells expressing aggregation-prone,

142 ts recognize antigen within intracytoplasmic inclusion bodies in ciliated bronchial epithelial cells

143 CMV colitis was diagnosed as having positive inclusion bodies in colonic tissue.

144 DS-PAGE and confocal microscopy the level of inclusion bodies in E. coli cells overexpressing the 40-

145 ballooning degeneration of and intranuclear inclusion bodies in epithelial cells, with HSV antigen i

146 antly nuclear RNA-binding protein that forms inclusion bodies in frontotemporal lobar degeneration (F

147 Electron microscopy showed inclusion bodies in neuronal processes and degenerating

148 Recombinant EnvD was recovered from inclusion bodies in soluble form from an Escherichia col

149 cp-A/1), form intracellular and intranuclear inclusion bodies in the brains of patients with Huntingt

150 hich infects cattle, does this by generating inclusion bodies in the cytoplasm of infected cells.

151 ing loss correlated with the accumulation of inclusion bodies in the satellite cells and their subseq

152 These results suggest that inclusion bodies in various forms of ALS result from a s

153 tructures containing microvilli (microvillus inclusion bodies) in epithelial enterocytes, a phenotype

154 gtin (Htt) is known to accumulate in compact inclusion bodies inside neurons, this is widely thought

155 R analysis suggested that the coalescence of inclusion bodies is a strategy to efficiently replicate

156 e protein tau aggregates and forms insoluble inclusion bodies known as neurofibrillary tangles in the

157 cells, members of the Reoviridae family form inclusion body-like structures known as viral inclusion

158 V viral RNA replication takes place in these inclusion bodies, likely meaning these organelles are a

159 At later times, the Sso AcP molecules in the inclusion bodies lose their native-like properties and c

160 Mammalian IPOD-like inclusion bodies, meanwhile, are not always inherited by

161 folded proteins typically aggregate and form inclusions bodies, membrane proteins that are addressed

162 oduce similar structures have suggested that inclusion bodies might be involved in genome replication

163 Both viruses form inclusion bodies, minimally composed of nucleoprotein (N

164 pathological features, including hereditary inclusion body myopathy (hIBM) and limb-girdle muscular

165 mplicated as potential mechanisms underlying inclusion body myopathy (IBM) and related disorders.

166 ns in valosin-containing protein (VCP) cause inclusion body myopathy (IBM) associated with Paget's di

167 disease of bone (PDB)-like syndrome-such as inclusion body myopathy (IBM) associated with Paget's di

168 ns in valosin-containing protein (VCP) cause inclusion body myopathy (IBM), Paget's disease of the bo

169 Inclusion body myopathy 3 (IBM-3) is an autosomal domina

170 in MEFs harboring a p97 mutation that causes inclusion body myopathy and neurodegeneration, and damag

171 Hereditary inclusion body myopathy associated with early-onset Page

172 d cause a multisystem degenerative disorder, inclusion body myopathy associated with Paget disease of

173 se a rare, autosomal dominant disease called inclusion body myopathy associated with Paget disease of

174 Here we have tested ten major inclusion body myopathy associated with Paget disease of

175 In the p97-associated human disease inclusion body myopathy associated with Paget disease of

176 linical multiple-disorder condition known as inclusion body myopathy associated with Paget's disease

177 ety of cellular activities) chaperone, cause inclusion body myopathy associated with Paget's disease

178 Inclusion body myopathy associated with Paget's disease

179 Inclusion body myopathy associated with Paget's disease

180 Inclusion body myopathy associated with Paget's disease

181 n of muscle shows classic characteristics of inclusion body myopathy including rimmed vacuoles and TD

182 n disease: amyotrophic lateral sclerosis and inclusion body myopathy with early-onset Paget disease a

183 sin-containing protein (VCP) mutations cause inclusion body myopathy with Paget disease and frontotem

184 Inclusion body myopathy with Paget disease of the bone a

185 found that in fibroblasts from patients with inclusion body myopathy with Paget's disease of bone and

186 nt for a spectrum of phenotypes that include inclusion body myopathy with Paget's disease of the bone

187 clerosis, frontotemporal lobar degeneration, inclusion body myopathy, and multisystem proteinopathy,

188 cause an autosomal dominant disease known as inclusion body myopathy, Paget disease with frontotempor

189 previously been identified in families with Inclusion Body Myopathy, Paget disease, and Frontotempor

190 also lead to TDP-43 deposition, resulting in Inclusion Body Myopathy, Paget disease, and Frontotempor

191 rmore, we show that a p97 mutant that causes inclusion body myopathy, Paget's disease of bone, and fr

192 VCP mutations are the cause of inclusion body myopathy, Paget's disease of the bone, an

193 e human GNE-opathies sialuria and hereditary inclusion body myopathy.

194 histologically distinct patient populations, inclusion body myositis (IBM) and anti-Jo-1-associated m

195 inst a 43 kDa muscle autoantigen in sporadic inclusion body myositis (IBM) and demonstrated the feasi

196 Historically, the diagnosis of sporadic inclusion body myositis (IBM) has required the demonstra

197 Inclusion body myositis (IBM) is a poorly understood aut

198 PURPOSE OF REVIEW: Inclusion body myositis (IBM) is a poorly understood pro

199 Inclusion body myositis (IBM) is often viewed as an enig

200 Inclusion body myositis (IBM), a degenerative and inflam

201 To examine new developments in sporadic inclusion body myositis (IBM), including updated clinica

202 genesis, diagnosis and treatment of sporadic inclusion body myositis (IBM).

203 arget of serum antibodies from patients with inclusion body myositis (IBM).

204 reatment and serum and imaging biomarkers of inclusion body myositis (IBM).

205 fications: dermatomyositis, polymyositis and inclusion body myositis (IBM).

206 eneration in myositis, focusing primarily on inclusion body myositis (IBM).

207 ata on 411 muscle samples from patients with inclusion body myositis (n = 40), other muscle diseases

208 Sporadic inclusion body myositis (sIBM) is a poorly understood im

209 Sporadic inclusion body myositis (sIBM) is an inflammatory myopat

210 the muscle fibers of patients with sporadic inclusion body myositis (sIBM) is unknown.

211 Sporadic inclusion body myositis (sIBM) pathogenesis is unknown;

212 TAR DNA binding protein TDP-43, in sporadic inclusion body myositis (sIBM) sarcoplasm are important

213 PM), Necrotizing Myositis (NM), and sporadic Inclusion Body Myositis (sIBM).

214 in the pathogenesis of familial and sporadic inclusion body myositis (sIBM).

215 in scattered muscle fibers occur in sporadic inclusion body myositis and clinically similar disorders

216 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Inclusion body myositis and T cell large granular lympho

217 itochondrial pathology (IM-VAMP), which have inclusion body myositis as a pathologic subtype and are

218 d an increase in KLRG1 expressing T cells in inclusion body myositis blood.

219 le, relative to placebo, in individuals with inclusion body myositis but did not improve 6MWD.

220 , we prospectively screened 38 patients with inclusion body myositis for the presence of expanded lar

221 Ultrasound has the ability to differentiate inclusion body myositis from other myopathies.

222 elated with the lower limb components of the inclusion body myositis functional rating score (rho=-0.

223 Most (22/38; 58%) patients with inclusion body myositis had aberrant populations of larg

224 Inclusion body myositis is a late onset treatment-refrac

225 Inclusion body myositis is an idiopathic inflammatory my

226 Although the cause of sporadic inclusion body myositis is unknown, GNE myopathy is asso

227 The extent of CD8+ and CD57+ cells in inclusion body myositis muscle correlated with the size

228 tified a signature of T-cell cytotoxicity in inclusion body myositis muscle coupled with a signature

229 entified the presence of KLRG1 on pathogenic inclusion body myositis muscle invading T cells and an i

230 We examined inclusion body myositis muscle T-cell proliferation by K

231 nflammatory responses that resemble sporadic inclusion body myositis pathology.

232 Here, we report on translational studies of inclusion body myositis patient muscle compared with a d

233 ge granular lymphocytes into muscle in 15/15 inclusion body myositis patients but in only 1/28 patien

234 eta-analysis of the apolipoprotein E gene in inclusion body myositis suggests that this gene does not

235 .3]) and MTR reduced compared with controls (inclusion body myositis thigh -1.5 percentage units [pu;

236 ared with controls (regression coefficients: inclusion body myositis thigh 4.0 ms [SE 0.5], calf 3.5

237 ith either Charcot-Marie-Tooth disease 1A or inclusion body myositis who were attending the inherited

238 forms are polymyositis, dermatomyositis, and inclusion body myositis) are systemic autoimmune disease

239 individual cells from patients with sporadic inclusion body myositis, a late-onset inflammatory myopa

240 Muscle biopsies from patients with sporadic inclusion body myositis, a well defined myopathy with ch

241 cot-Marie-Tooth disease 1A, 20 patients with inclusion body myositis, and 29 healthy controls (alloca

242 domised controlled trial done in people with inclusion body myositis, and it provides important natur

243 In polymyositis and inclusion body myositis, muscle fibers are surrounded an

244 In many patients with inclusion body myositis, the autoimmune T cell expansion

245 ciated with aging and is related to sporadic inclusion body myositis, the most common acquired muscle

246 Inclusion body myositis, the most common muscle disorder

247 ly definite by MRC criteria was required for inclusion body myositis.

248 genotype confers the highest disease risk in inclusion body myositis.

249 r focus on polymyositis, dermatomyositis and inclusion body myositis.

250 mulate intracellularly in some patients with inclusion body myositis.

251 includes polymyositis, dermatomyositis, and inclusion body myositis.

252 omprising dermatomyositis, polymyositis, and inclusion body myositis.

253 sent key early events in the pathogenesis of inclusion body myositis.

254 s are potential disease activity sensors for inclusion body myositis.

255 vided into dermatomyositis, polymyositis and inclusion body myositis.

256 uld be a favourable approach to treatment of inclusion body myositis.

257 ive muscle disease of aging humans, sporadic inclusion body myositis.

258 ulates early in Alzheimer's disease (AD) and inclusion body myositis.

259 uman monoclonal antibody-in individuals with inclusion body myositis.

260 d 2010 Medical Research Council criteria for inclusion body myositis.

261 ntotemporal lobar degeneration, and sporadic inclusion body myositis.

262 l (3.3%, 1.8-4.9, p=0.0007) in patients with inclusion body myositis.

263 Sporadic inclusion-body myositis (IBM) is the most common muscle

264 The hallmark pathologies of sporadic inclusion-body myositis (s-IBM) muscle fibers are autoph

265 Sporadic inclusion-body myositis (sIBM) is the most common disabl

266 y provides insights into the pathogenesis of inclusion-body myositis and concludes that in sIBM one s

267 Inclusion bodies of aggregated mutant huntingtin (htt) f

268 The aggregation and inclusion bodies of alpha-synuclein with ubiquitin are p

269 is a rare recessive myopathy associated with inclusion bodies on muscle biopsy.

270 tia familial encephalopathy with neuroserpin inclusion bodies or FENIB.

271 smic replicating viruses produce cytoplasmic inclusion bodies or protein aggregates; however, a hallm

272 concentrated at aggresomes and other related inclusion bodies prevalent in neurodegenerative disease.

273 of murine BTNL2 was expressed in bacteria as inclusion bodies, refolded in vitro and purified for fun

274 ral lobar dementia (FTLD) with ubiquitinated inclusion bodies show TDP-43 pathology, the protein enco

275 This excess ferritin L-chain was found in inclusion bodies, some of which were co-localized with l

276 though little is known of the nature of the inclusion body structures.

277 The IF-MoS2 and INT-WS2 reside in vesicles/inclusion bodies, suggestive of endocytic vesicles.

278 on-prone and form a variety of intracellular inclusion bodies that are characteristic of different ne

279 accumulation of alpha-synuclein constitutes inclusion bodies that are considered a characteristic fe

280 coli frequently results in the production of inclusion bodies that are subsequently used to produce f

281 essing N586-82Q accumulate large cytoplasmic inclusion bodies that can be visualized with antibodies

282 s, UCH-L1 is also found in the ubiquitinated inclusion bodies that characterize neurodegenerative dis

283 Such proteins formed inclusion bodies that could be resolved by HSF1 activati

284 growth and is enriched in cytoplasmic viral inclusion bodies that include viral proteins responsible

285 Carboxysomes are polyhedral inclusion bodies that play a key role in autotrophic met

286 gresomes are transient microtubule-dependent inclusion bodies that sequester misfolded proteins and a

287 to trigger the formation of WDR5-containing inclusion bodies, that these structures display properti

288 tein was expressed in E. coli in the form of inclusion bodies, the protein could misfold during expre

289 s, indicating detection of phospholipid-rich inclusion bodies typical for cells with DIPL.

290 that ubiquitylated proteins are directed to inclusion bodies under stress conditions, when both chap

291 nclusion body-like structures known as viral inclusion bodies (VIB) or viral factories.

292 phosphorylation level and assembly of viral inclusion bodies (VIBs) were reduced.

293 d double-stranded RNA synthesis within viral inclusion bodies (VIBs).

294 In order to study filovirus inclusion bodies, we fused mCherry to the ebolavirus pol

295 d secretion so that only small quantities of inclusion bodies were detected.

296 Inclusion bodies were not necessary for the toxicity and

297 Large, heterogeneous inclusion bodies were observed in cells of mutants inact

298 despread accumulation of the typical storage inclusion bodies were the major histological findings in

299 GSAP is expressed in inclusion bodies, which can be solubilized using harsh d

300 ontaining proteins by refolding from E. coli inclusion bodies, which would not normally be amenable t