ライフサイエンスコーパス: myelinate

1 nd adolescence, as fibre bundles develop and myelinate.

2 onding to fast temporal frequencies are more myelinated.

3 gested about 57% of penile nerve fibers were myelinated.

4 thin during childhood but instead gets more myelinated.

5 xon diameters than PV+ cells, and are rarely myelinated.

6 al nervous system (PNS), Schwann cells (SCs) myelinate a single axon.

7 ections of cholera toxin subunit B (CTB) for myelinated A fibers and isolectin B4 (IB4) for unmyelina

8 Large diameter sensory myelinated (Abeta) fibres are more frequently involved,

9 as focused on signaling systems that promote myelinating activity of oligodendrocytes or promote prod

10 ogeneous group of disorders affecting thinly myelinated Adelta-fibres and unmyelinated C-fibres.

11 e more frequently involved, but motor, small myelinated (Adelta), unmyelinated (C) or autonomic fibre

12 d and high-frequency AP conduction along the myelinated afferent nerves, and loss of function of thes

13 In myelinated afferents, nodal length increased postoperati

14 emerge unmyelinated from the eye and become myelinated after passage through the optic nerve lamina

15 unonegative nerves are strikingly similar to myelinated airway afferents, the cough receptor, and smo

16 generative diseases as oligodendrocytes both myelinate and provide metabolic support to axons.

17 ies show that SCs retain their plasticity to myelinate and remodel myelin via mTORC1 throughout life.

18 hGCs interact with myelinated and non-myelinated axons through the formatio

19 revealing differentiable fatty acyl pools in myelinated and nonmyelinated regions.

20 rves, ERK1/2 phosphorylation was observed in myelinated and nonmyelinating SCs.

21 The auditory system is heavily myelinated and operates at the upper limits of action po

22 AAVrh10 has higher tropic affinity to large myelinated and small peptidergic sensory neurons that in

23 gical and functional studies to assess large myelinated and small unmyelinated axons in the db/db typ

24 action potential conduction velocity in both myelinated and unmyelinated central axons can be bidirec

25 long-distance (>25 mm) regeneration of both myelinated and unmyelinated sensory axons with topograph

26 rized by terminal differentiation defects in myelinating and non-myelinating Schwann cells and immune

27 ncreased myelination with about 40% of axons myelinated, and an enhanced locomotor function (score of

28 ssive MS is mainly due to the higher rate of myelinated axon degeneration, coupled to the lower capac

29 tor marker; CGRP), and/or neurofilament 200 (myelinated axon marker; NF200).

30 Distal myelinated axon outgrowth after 4 weeks was quantified u

31 ary conductive component to accurately model myelinated axon physiology and saltatory conduction.

32 their myelin sheaths to fully understand how myelinated axon plasticity contributes to neuronal circu

33 rd, expression of Nogo-A was associated with myelinated axon tracts and upregulated in oligodendrocyt

34 vier is a functionally important site on the myelinated axon where sodium channels are clustered and

35 components of the nodes of Ranvier and other myelinated axonal domains in sensory neurons cultured al

36 hese interactions are mediated by long-range myelinated axonal fiber bundles, collectively termed as

37 size dramatically increased the frequency of myelinated axonal segments.

38 at GlcNAc6ST-1 modulates PNS myelination and myelinated axonal survival through the GlcNAc-6-O-sulfat

39 Oligodendrocytes myelinate axons in the central nervous system and develo

40 nteract with neurons and the basal lamina to myelinate axons using known receptors, signals and trans

41 fferentiate into mature oligodendrocytes and myelinate axons.

42 duced Ca(2+) influx, some active in normally-myelinated axons (T-type channels, NCX), others active o

43 ronal processes, permitting us to survey all myelinated axons (the projectome).

44 a significant decrease in the percentage of myelinated axons and a substantial increase in the mean

45 d an important decrease in the percentage of myelinated axons and a substantial increase in the mean

46 distance-dependent ephaptic coupling between myelinated axons and between fascicles as well.

47 affecting auditory ganglion cells and their myelinated axons and dendrites; and (iv) central neural

48 ny cell adhesion molecules are present along myelinated axons and in myelinating glia, but functional

49 zed by small reductions in the percentage of myelinated axons and minor changes in the g-ratio of mye

50 in hypomyelination (i.e., reduced number of myelinated axons and thinner myelin profiles), as well a

51 ortant axonal domains.SIGNIFICANCE STATEMENT Myelinated axons are constricted at nodes of Ranvier, re

52 Myelinated axons are constricted at nodes of Ranvier.

53 Myelinated axons can conduct sustained trains of impulse

54 substantial increase in the mean g-ratio of myelinated axons compared with controls.

55 Imaging of neurofilament transport in mature myelinated axons ex vivo reveals that neurofilament poly

56 s (Kv1 channels) within the nodal complex of myelinated axons following injury.

57 relates of this adjacent injury in surviving myelinated axons have not been previously defined.

58 nerve fibres and significant degeneration of myelinated axons in both the distal sural nerve and nerv

59 ccess to the nanostructural dynamics of live myelinated axons in health and disease.

60 eostasis, we asked whether the disruption to myelinated axons in slc12a2b/NKCC1b mutants is affected

61 particularly from the brainstem, and more SC-myelinated axons in the implants and improvement in hind

62 domains (the paranode and juxtaparanode) of myelinated axons in the pathology of acquired, inflammat

63 not lose unmyelinated fibres in the skin or myelinated axons in the sural nerve and toe after vincri

64 flected light, enabling nanoscale imaging of myelinated axons in their natural living state.

65 onal activity regulates oligodendrocytes and myelinated axons in vivo, with a focus on the timing of

66 cise fine-tuning of conduction along already-myelinated axons may also be mediated by alterations to

67 In peripheral myelinated axons of mammalian spinal motor neurons, Ca(2

68 ury, when nerve repair is normally advanced, myelinated axons of MEK1DD mutants demonstrated higher r

69 to analyze neurofilament transport in mature myelinated axons of tibial nerves from male and female m

70 We previously reported that pain and myelinated axons regenerating through a Y-shaped nerve g

71 tion potential initiation and propagation in myelinated axons require ion channel clustering at axon

72 es of Ranvier are the myelin-free gaps along myelinated axons that allow fast communication between n

73 Herceptin also increased the number of myelinated axons that regenerated 4 weeks after immediat

74 hGCs interact with myelinated and non-myelinated axons through the formation of pseudopodia.

75 Finally, oligodendrocytes and myelinated axons were analyzed using stereology and cohe

76 that the functional capacity of the heavily myelinated axons were preferentially compromised, leadin

77 icient mice of both sexes and found that, in myelinated axons, alphaII spectrin forms a periodic cyto

78 y describe the organization of myelin and of myelinated axons, as well as the functions of myelin in

79 own that white matter, primarily composed of myelinated axons, can also be dynamically regulated by a

80 In myelinated axons, it also enhances myelin thickness thro

81 ence of cerebral oedema, loss of neurons and myelinated axons, microglial proliferation and reactive

82 found at greater densities in large-diameter myelinated axons, suggesting that nodes are particularly

83 channels at nodes of Ranvier, a hallmark of myelinated axons, underlies effective saltatory conducti

84 ic protein highly expressed in large calibre myelinated axons.

85 ct myelin lipid composition and stability of myelinated axons.

86 ine structures including cortical layers and myelinated axons.

87 of myelin proteins and in the percentage of myelinated axons.

88 preferential degeneration of large-diameter myelinated axons.

89 nd efficient action potential propagation in myelinated axons.

90 cal for fast action potential propagation in myelinated axons.

91 preferential degeneration of large-diameter myelinated axons.

92 axon-myelin interface, and the integrity of myelinated axons.

93 anges were accompanied by reduced numbers of myelinated axons.

94 d filaments that extend longitudinally along myelinated axons.

95 substantial increase in the mean g-ratio of myelinated axons.

96 med in one case revealed subtotal absence of myelinated axons.

97 a general marker of damage to large-caliber myelinated axons.

98 ial for effective saltatory conduction along myelinated axons.

99 mechanism of current flux minimization along myelinated axons.

100 a substantial reduction in the percentage of myelinated axons.

101 er dorsal-root ganglion (L-DRG) neurons with myelinated axons.

102 rapid propagation of action potentials along myelinated axons.

103 ate-like junctions of peripheral and central myelinated axons.

104 microglia were found to structurally damage myelinated axons.

105 ed axons and minor changes in the g-ratio of myelinated axons.

106 them toward a close spatial association with myelinated axons.

107 erved across the brain, particularly in late myelinating brain regions such as frontal white matter a

108 endothelin levels, which in turn affect the myelinating capacity of oligodendrocytes.

109 ndicate that neuronal activity regulates the myelinating capacity of single oligodendrocytes.

110 SCF (SKP1, Cul1, F-box protein) expressed in myelinating cells affects the axon-myelin unit.

111 for their timely differentiation to mature, myelinating cells and plays a crucial role in radial axo

112 k-out in male mice improves replenishment of myelinating cells and remyelinated nerve fibers and slow

113 study, we constitutively overexpress CHOP in myelinating cells during development and into adulthood

114 Here, we report that deletion of Fbxo7 in myelinating cells in mice triggered motor impairment but

115 Myelinating cells of the CNS [oligodendrocytes (OLs)] ar

116 Schwann cells (SCs) are myelinating cells of the PNS.

117 s demonstrate an essential role for FBXO7 in myelinating cells to support associated axons, which is

118 the effect of modulating ERK1/2 activity in myelinating cells using transgenic mouse lines in which

119 (Ac-eEF1A1) translocates into the nucleus of myelinating cells where it binds to Sox10, a key transcr

120 It did not result in apoptosis of myelinating cells, nor did it affect the proper myelinat

121 emarkably, when repair cells transit back to myelinating cells, they shorten approximately 7-fold to

122 al progenitors that generate both classes of myelinating cells.

123 and proliferate before differentiating into myelinating cells.

124 could, in fact, have detrimental effects on myelinating cells.

125 In the CNS, oligodendrocytes act as the myelinating cells.

126 d brain, discrete nuclei form interconnected myelinated circuits that control song acquisition and pr

127 purified spinal cord neuron-oligodendrocyte myelinating co-culture system, we demonstrate that disru

128 Myelinating co-cultures using human induced pluripotent

129 uced for the first time long-term and stable myelinating co-cultures with human neurons.

130 a computational model of a single mammalian myelinated cochlear nerve fiber coupled to a stimulator-

131 Moreover, in pHERV-W ENV-stimulated myelinated cocultures, microglia were found to structura

132 Evoked action potentials in the myelinated corpus callosum projections of Msh2-null mice

133 nificantly differed between demyelinated and myelinated cortex (p < 0.001).

134 alysis of fluorescent micrographs such as 2D-myelinating cultures and statistical analysis using R.

135 1/TLD cleavage site in gliomedin or treating myelinating cultures with a Bmp1/TLD inhibitor results i

136 , in the strong coupling regime, relevant to myelinated dendritic trees, the spike train statistics c

137 Unmyelinated epidermal nerve fiber and myelinated dermal nerve fiber densities were quantified

138 Therefore, YAP/TAZ are crucial for SCs to myelinate developing nerve and to maintain myelinated ne

139 and the pathobiology of various de- and dys-myelinating disorders.

140 on in certain sensory neurons, which possess myelinated distal dendritic tree-like arbors with excita

141 -term engrafted glial-restricted progenitors myelinated dysmyelinated adult mouse brains within one m

142 ts anti-inflammatory, antioxidative, and pro-myelinating effects.

143 system that oligodendrocytes preferentially myelinate electrically active axons, but synapses from a

144 traepidermal nerve fibers and intrapapillary myelinated endings remained unchanged, but the caliber o

145 unchanged, but the caliber of intrapapillary myelinated endings was increased.

146 traepidermal nerve fibers and intrapapillary myelinated endings was reduced.

147 These cells myelinate fewer axons than in wild-type mice and, in cor

148 titative stereologic analysis showed reduced myelinated fiber length and density.

149 aPOZ mice are impaired in the maintenance of myelinated fibers and are a promising model for studying

150 portance of sensory input in the building of myelinated fibers and suggest that this activity-depende

151 osarcoma, and irregularity and disruption of myelinated fibers in areas infiltrated by oligodendrogli

152 f IQCJ-SCHIP1 in vivo by studying peripheral myelinated fibers in Schip1 knock-out mutant mice.

153 The mean number of myelinated fibers in the sural nerve was significantly l

154 Myelinated fibers showed caliber reduction and nodal elo

155 We found evidence for two classes of myelinated fibers within the pinniped optic nerve, those

156 ect on neurite outgrowth and regeneration of myelinated fibers without affecting unmyelinated DRG neu

157 l regions for action potential conduction in myelinated fibers.

158 out affecting other structural properties of myelinated fibers.

159 red to vehicle, suggesting more functionally myelinated fibers.

160 affected individuals showed a severe loss of myelinated fibres and abnormalities in the paranodal jun

161 The assembly of myelinated fibres and nodes of Ranvier is mediated by a

162 Immunofluorescence staining of myelinated fibres from two affected individuals showed a

163 Loss of large-myelinated fibres was a uniform feature in a total of 21

164 Studies of myelinated fibres, however, show that voltage-gated sodi

165 ed by immunofluorescence labelling of dermal myelinated fibres.

166 suggest that lateral VTC likely becomes more myelinated from childhood to adulthood, affecting the co

167 -specific phenolic glycolipid 1 (PGL-1) with myelinating glia and their subsequent infection.

168 at mediate interactions between the axon and myelinating glia at the nodal gap (i.e., NF186) and the

169 Schwann cells are myelinating glia in the peripheral nervous system that f

170 Schwann cells are the myelinating glia of the peripheral nervous system and dy

171 Myelinating glia play a fundamental role in promoting th

172 In myelinating glia, autophagy has expanded roles, particul

173 es are present along myelinated axons and in myelinating glia, but functional interactions among thes

174 Loss of Fbxo7 in myelinating glia, however, led to axonal degeneration in

175 t, several neural crest-derived lineages and myelinating glia.

176 rocyte progenitor cells (OPCs), the resident myelinating glial cell of the CNS, into the periphery.

177 a prodeath protein, and we demonstrate that myelinating glial cells function normally in the presenc

178 Following perturbations to peripheral myelinating glial cells, centrally derived oligodendrocy

179 irst biomimetic microphysiological system of myelinated human peripheral nerve which can be used for

180 a-afferent neurons, or in Schwann cells that myelinate Ia-afferent axons remains unresolved.

181 tor cells fail to properly differentiate and myelinate in the mouse brain due to cell-intrinsic trans

182 r, we found that cortex was thicker and more myelinated in genetic voxels of face areas, while it was

183 of face areas, while it was thinner and less myelinated in genetic voxels of place areas.

184 in-positive (PV) interneurons are frequently myelinated in the cerebral cortex.

185 ascending (CoPA) neurons are among the first myelinated in the zebrafish CNS.

186 uctural plasticity has come to light for the myelinated infrastructure of the nervous system.

187 st sort and ensheathe a single axon and then myelinate it.

188 d that Ube3a is expressed monoallelically in myelinated large-diameter neurons and biallelically in u

189 ssed from the maternally inherited allele in myelinated large-diameter sensory neurons and biallelica

190 Type I afferents are myelinated, larger diameter neurons that send a single d

191 y discriminable but similar deficits in well myelinated mice in which glial cells cannot fully suppor

192 The Ca(2+) that enters myelinated motor axons during normal activity is likely

193 sin-positive synapses or mtHSP70 was seen in myelinated MS hippocampi, further pointing toward a link

194 icker myelin sheaths and sometimes appear to myelinate multiple axons in a fashion reminiscent of oli

195 ntral nervous system (CNS), oligodendrocytes myelinate multiple axons; in the peripheral nervous syst

196 ls named Schwann cells (SCs) that are either myelinating (mySCs) or nonmyelinating (nmSCs).

197 inal pigment epithelium degeneration (2.5%), myelinated nerve fiber layer (1.3%), and internal limiti

198 erest because the global effects of aging on myelinated nerve fibers are more complex and profound th

199 Approximately 80 percent of myelinated nerve fibers throughout the central and perip

200 adhesion molecules, such as MAG, present in myelinated nerve fibers.

201 the action potential propagating elements of myelinated nerve fibers.

202 14 cutaneous nerve biopsies revealed loss of myelinated nerve fibres (86%), increased regenerative cl

203 o myelinate developing nerve and to maintain myelinated nerve in adulthood.

204 ciated glycolipids essential for maintaining myelinated nerve integrity.

205 Rapid nerve conduction in myelinated nerves requires the clustering of voltage-gat

206 an be regenerated during nerve conduction on myelinated nerves, ion channel mechanisms underlying the

207 response protein 2) transcription factors in myelinated nerves.

208 aps through the nodes of Ranvier (NRs) along myelinated nerves.

209 e significantly impaired in their ability to myelinate neurites in vitro To our knowledge, this is th

210 Nodes of Ranvier in the axons of myelinated neurons are exemplars of the specialized cell

211 A second channel found in larger myelinated neurons, Nav1.6, subsequently evolved resista

212 they matured over time in vitro and started myelinating neurons.

213 nd the marrow cavity were each innervated by myelinated (NF200+) sensory neurons, and unmyelinated (N

214 programs governing myelination, and acts on myelinating oligodendrocyte (OL) cells across the human

215 1/5/8 and inhibits OPC differentiation into myelinating oligodendrocytes (OLs) while promoting an as

216 ied by an important decline in the number of myelinating oligodendrocytes and in the rate of OPC prol

217 ied by an important decline in the number of myelinating oligodendrocytes and in the rate of OPC prol

218 as accompanied by a decline in the number of myelinating oligodendrocytes and with a reduction in pro

219 nitor cells (OPCs), which differentiate into myelinating oligodendrocytes during CNS development, are

220 Myelinating oligodendrocytes enable fast propagation of

221 development in rats, a subpopulation of pre-myelinating oligodendrocytes in the auditory brainstem r

222 cells to proliferate and differentiate into myelinating oligodendrocytes in the medial prefrontal co

223 Thus, decoding how OPCs and myelinating oligodendrocytes integrate and process Ca(2+

224 mate instruct OPCs to differentiate into new myelinating oligodendrocytes that recover lost function.

225 Some OPCs differentiate rapidly as myelinating oligodendrocytes, whereas others remain into

226 ing B(regs) treatment and differentiate into myelinating oligodendrocytes, which results in neo-oligo

227 e progenitor cells from differentiating into myelinating oligodendrocytes.

228 areas or OPCs in lesions may not mature into myelinating oligodendrocytes.

229 rocyte development, but are downregulated in myelinating oligodendrocytes.

230 A subpopulation of pre-myelinating OLs (pre-OLs) can generate Nav1.2-driven act

231 is selectively expressed in differentiating/myelinating OLs.

232 When myelinated optic nerves from conditional NMDA receptor m

233 injured spinal cord; invasion of peripheral myelinating (P0+) Schwann cells made only a limited cont

234 hich OPCs migrate out of the spinal cord and myelinate peripheral motor axons, we assayed perineurial

235 (OPCs) ectopically exit the spinal cord and myelinate peripheral nerves in myelin with CNS character

236 12 status displayed improved conductivity in myelinated peripheral nerves after vitamin B-12 treatmen

237 ced consistent improvements in conduction in myelinated peripheral nerves; the sensory latency of bot

238 While oligodendrocytes are capable of myelinating permissive structures in the absence of mole

239 myelinated retinal nerve fiber layer and the myelinated post-laminar axons, as well as olygodendrocyt

240 nsistent with possible direct effects on the myelinating potential of oligodendrocyte progenitor cell

241 Our data reveal unexpected plasticity in the myelinating potential of SCs, which may have important i

242 E3 ubiquitin ligase component, enhances the myelinating potential of SCs.

243 Why are the myelinating potentials of these glia so fundamentally di

244 Time-lapse imaging reveals that the distinct myelinating processes of individual oligodendrocytes can

245 ived oligodendrocytes are functional and can myelinate rat dorsal root ganglion neurons in vitro, and

246 f active enhancers, to identify enhancers in myelinating rat peripheral nerve and their dynamics afte

247 lasticity of Schwann cells allows them to re-myelinate regenerated axons following injury and we show

248 tra-axonal diffusion microenvironment; while myelinated regions showed no changes.

249 De, perpendicular in both premyelination and myelinated regions, indicative of both intra- and extra-

250 observations that V3d and PO/V6 are densely myelinated relative to adjacent cortex and share similar

251 Krox20 and, without them, completely fail to myelinate, resulting in severe peripheral neuropathy.

252 hich reveal remarkable bilateral symmetry in myelinated reticulospinal and lateral line afferent axon

253 driving axonal wrapping by unmyelinated and myelinated Schwann cells and enhancing myelin protein sy

254 g SMA mice selectively overexpressing SMN in myelinating Schwann cells (Smn(-/-);SMN2(tg/0);SMN1(SC))

255 fferentiation defects in myelinating and non-myelinating Schwann cells and immune cell activation.

256 which correlated with a reduced presence of myelinating Schwann cells and increased numbers of nonmy

257 itionally deleted the MHC-II beta-chain from myelinating Schwann cells in mice and investigated how t

258 model by deleting GALCLAMP1 specifically in myelinating Schwann cells in order to characterize the p

259 OPCs also produced the majority of myelinating Schwann cells in the injured spinal cord; in

260 tes in the central nervous system (CNS), non-myelinating Schwann cells in the peripheral nervous syst

261 loss of slc12a2b/NKCC1b in either neurons or myelinating Schwann cells recapitulated these pathologie

262 We demonstrate that deletion of MHC-II in myelinating Schwann cells reduces thermal hyperalgesia a

263 To develop a gene therapy approach targeting myelinating Schwann cells that can be translatable, we d

264 We report for the first time, defects in myelinating Schwann cells, enteric neurons and pigment c

265 P0 is synthesized by myelinating Schwann cells, processed in the endoplasmic

266 ed domains formed by axonal interaction with myelinating Schwann cells, such as clustered voltage-gat

267 ls and enhancing myelin protein synthesis in myelinating Schwann cells.

268 control of the Mpz promoter specifically in myelinating Schwann cells.

269 Analyses of gene expression arrays of large myelinated sciatic nerves from pioglitazone-treated anim

270 tor (DTR) preferentially in tSCs compared to myelinating SCs followed by local application of diphthe

271 viously thought to fundamentally distinguish myelinating SCs from oligodendrocytes.

272 t led to abnormalities in nonmyelinating and myelinating SCs in the later phases of nerve repair, res

273 contrast, deleting these proteins in mature myelinating SCs results in milder phenotypes characteriz

274 nuclear YAP/TAZ are selectively expressed by myelinating SCs, and conditional ablation results in sev

275 ARTN promotes robust regeneration of large, myelinated sensory afferents.

276 between db/db and db/+ mice studies of large myelinated sensory and motor nerves.

277 ozygote mice already have reduced numbers of myelinated sensory axons at 1.5 months and lose more axo

278 chanism to suppress the hyperexcitability of myelinated sensory axons that follows nerve injury.

279 associated with hyperexcitability in damaged myelinated sensory axons, which begins to normalise over

280 P), peptidergic nociceptors (PEP), and large myelinated sensory neurons (LM) under both control and i

281 de novo ensheathment of approximately 30% of myelinated spinal axons at injury epicenter 3 months aft

282 xcitability in relation to maturation to the myelinating stage are controversial, although oligodendr

283 ived oligodendrocytes can develop to the pre-myelinating stage, but subsequently undergo cell death.

284 ocks Schwann cell differentiation at the pro-myelinating stage, whereas overexpression of CTCF promot

285 ), primarily localized by Perls' staining to myelinated structures.

286 larly vulnerable brain compartment, the late myelinating superficial white matter.

287 ic Schwann cells (PSCs) are specialized, non-myelinating, synaptic glia of the neuromuscular junction

288 ce between nerve and muscle and includes non-myelinating terminal Schwann cells (tSCs).

289 ciation cortical areas were thicker and less myelinated than primary cortical areas at 14 y.

290 emonstrate that iPSC-derived OL disperse and myelinate the CNS of Mbp(shi/shi)Rag(-/-) mice during de

291 We further show that, when SCs become myelinating, they downregulate functional AMPARs.

292 mentations are then used to track volumes of myelinated tissues in the regions of the central brain s

293 Schwann cell dedifferentiation from a myelinating to a progenitor-like cell underlies the rema

294 hus, microglia and low-grade inflammation of myelinated tracts emerged as the trigger of a previously

295 ain by the predominant (95%) large-diameter, myelinated type I afferents, each of which is postsynapt

296 l recovery is accompanied by preservation of myelinated white matter and motor neurons and an increas

297 Myelinated white matter supports the speed of electrical

298 Late-myelinating white matter is more susceptible to age-rela

299 susceptible to age-related change than early-myelinating white matter, consistent with the retrogenes

300 mouse optic nerve, which is a pure and fully myelinated WM tract, aging axons are larger, have thicke