ライフサイエンスコーパス: horn

1 nd inferior olive), and spinal cord (ventral horn).

2 ctivity to the mushroom body and the lateral horn.

3 of double labeling in the superficial dorsal horn.

4 -facilitated CaV2.2 expression in the dorsal horn.

5 elated peptide (CGRP) staining in the dorsal horn.

6 solidation-like effects in the spinal dorsal horn.

7 ium to develop extrusion outside the uterine horn.

8 pled to motor networks in the spinal ventral horn.

9 n behaviors and BIP expression in the dorsal horn.

10 n was significantly stiffer than the ventral horn.

11 us adenosine tone is increased in the dorsal horn.

12 y synaptic transmission in the spinal dorsal horn.

13 ly elevated in the ipsilateral spinal dorsal horn.

14 h microglial activation in the dorsal spinal horn.

15 uron of superficial laminae of dorsal spinal horn.

16 related peptide-labeled fibers in the dorsal horn.

17 c transmission within the superficial dorsal horn.

18 diate area, and motor neurons in the ventral horn.

19 in pain signaling in the spinal cord dorsal horn.

20 ns, including neuronal NOS (nNOS), in dorsal horn.

21 of glomerular projections target the lateral horn.

22 minals in the superficial spinal cord dorsal horn.

23 ted by inhibitory interneurons in the dorsal horn.

24 n these two populations in the medial dorsal horn.

25 ion exhibited CASP6 activation in the dorsal horn.

26 in postsynaptic neurons in the spinal dorsal horn.

27 stinct neuroanatomic loci within the lateral horn.

28 dalis (Vc), the homolog of the spinal dorsal horn.

29 ds by gating mechanical inputs in the dorsal horn.

30 these cells in the superficial spinal dorsal horn.

31 ng to a decision neuron (LHN) in the lateral horn.

32 a membranes (SPMs) of the ipsilateral dorsal horn.

33 CaV2.2 expression in the SPMs of the dorsal horn.

34 n neurons in the spinal and medullary dorsal horn.

35 ateral (iVH) and contralateral (cVH) ventral horns.

36 ell as in iVH and contralateral dorsal (cDH) horns.

37 rring between ipsilateral dorsal and ventral horns.

38 and between left and right dorsal (sensory) horns.

39 nd both labels were quantified in the dorsal horns.

40 descending projections to the spinal dorsal horn [1].

41 d II neurons within the rodent spinal dorsal horn, a principal site of action for opiate analgesia.

42 hips between the different sensory and motor horns, a pattern that was similar to activation patterns

43 rge and unique repertoire identified in head horns, a recent morphological innovation.

44 itivity at excitatory synapses in the dorsal horn after nerve injury suggest that new generation PAMs

45 neurons (not glia) of the superficial dorsal horn after noxious heat stimuli.

46 esent in lamina II of the superficial dorsal horn, an area involved in nociception.

47 ts, in the developmental evolution of beetle horns, an evolutionary novelty, and horn polyphenisms, a

48 gical evidence of reconnection to the dorsal horn and behavioral recovery in mechanical pressure, the

49 in laminae I and V of the spinal cord dorsal horn and caudal spinal trigeminal nucleus and in the nuc

50 ents, which terminate medially in the dorsal horn and dorsolaterally in nTTD, terminate in specific c

51 ated p38 MAPK immunoreactivity in the dorsal horn and Iba1 and cluster of differentiation 45 expressi

52 ing of nociceptive information in the dorsal horn and in the generation of central sensitization duri

53 to higher brain areas including the lateral horn and mushroom body.

54 lbumin-expressing interneurons in the dorsal horn and represents a pharmacological target to manipula

55 tic tracing of genetically identified dorsal horn and RVM neurons to uncover an RVM-spinal cord-prima

56 Hz) frequency oscillations within the dorsal horn and somatosensory thalamus.

57 ers of GLT1-expressing astrocytes in ventral horn and total intraspinal GLT1 protein expression were

58 in the lower cranial nerve nuclei, anterior horns and corresponding nerves, atrophy of the spinothal

59 These include loss of lower (ventral horn) and upper motor neurons (corticospinal motor neuro

60 eurons around the antennal lobe, the lateral horn, and the posterior superior lateral protocerebrum.

61 ivity between left and right ventral (motor) horns, and between left and right dorsal (sensory) horns

62 ration) or weapon morphology (e.g., antlers, horns, and canines).

63 al correlations in the ventral horns, dorsal horns, and central spinal cord gray matter.

64 e beam when the lens is applied to a conical horn antenna.

65 These lack fully assembled horn appendages.

66 dels in which afferent inputs in the ventral horn are dramatically reduced (ER81(-/-) knockout), weak

67 expressing neurons of the superficial dorsal horn are predominantly interneurons, that a small number

68 VM1-PN axonal projections within the lateral horn are topographically segregated from those of V-PN a

69 We find that horns are both stronger and stiffer in response to speci

70 ogy of HIF-AuNR@AuPd and identified that the horns are bound with high-index {11l} (0.25 < l < 0.43)

71 synaptic strength at the level of the dorsal horn as an underlying mechanism.

72 ate transporter, GLT1, in superficial dorsal horn astrocytes are associated with both excitability ch

73 ch it mediates sex-specific development in a horned beetle species by combining systemic dsx knockdow

74 conserved during development of Onthophagus horned beetles and have retained the ability to regulate

75 Within the dorsal horn, besides KChIP3 in the inner lamina II and lamina I

76 ered, approximately 120,000-y-old giant long-horned bison, Bison latifrons, from Snowmass, Colorado.

77 ibition and returns a highly derived sigmoid horn body size allometry to its presumed ancestral, line

78 rget regions: the mushroom body, the lateral horn (both of which are well known centres for sensory p

79 ia and reduced CGRP expression in the dorsal horn caudal to the lesion.

80 me 1 and lethal arthrogryposis with anterior horn cell disease are autosomal recessive fetal motor ne

81 uropathic pain behavior and increased dorsal horn cell sensitivity to cutaneous mechanical and cold s

82 motor nerve up to the level of the anterior horn cell.

83 ntral grey matter, with predominant anterior horn-cell involvement, and nine (75%) children had brain

84 ern: a symmetric involvement of the anterior horn cells.

85 The horned, ceratopsid dinosaurs can be easily split into tw

86 tion of key components of the elusive dorsal horn circuit for mechanical allodynia.

87 hlights the complexity of superficial dorsal horn circuitry and addresses the question whether the pr

88 MGE-derived neuronal precursors into dorsal horn circuitry in intact, adult mice with short- (5-6 we

89 ion in the development of nociceptive dorsal horn circuits critical for mechanical and thermal pain p

90 By examining the dorsal horn circuits that underlie the transmission of "pain" a

91 rocesses in superficial layers of the dorsal horn, commissural neurons in the intermediate area, and

92 ned the strength of the intrasegment horn-to-horn connectivity only on the injury side and in slices

93 -opioid receptors (MOR) in the spinal dorsal horn constitutively repress the expression of synaptic l

94 The superficial spinal dorsal horn contains a heterogeneous population of neurons that

95 ased stereotyped connectivity of the lateral horn contrasts with the probabilistic wiring of the mush

96 enhancing glycinergic tone within the dorsal horn could obtund nociceptor signaling to the brain and

97 n the trypanotolerant N'Dama, coat color and horn development in Ankole, and heat tolerance and tick

98 dorsal horn neurons and critical for dorsal horn development, is expressed in nociceptive dorsal hor

99 ing and the descending control of the dorsal horn (DH) by brain regions such as the periaqueductal gr

100 gonize each other through spinal cord dorsal horn (DH) gating neurons.

101 ABSTRACT: The dorsal horn (DH) of the spinal cord is an important site for mo

102 es changes in sensory circuits of the dorsal horn (DH) where nociceptive inputs integrate for pain pr

103 regions of the CNS, including in the dorsal horn (DH), its contribution to pain remains undefined.

104 We now report that the uterine horn dilation correlates with glandular duct dilation de

105 Screening 12 strains of mice for uterine horn dilation following C. muridarum infection revealed

106 The severity scores of uterine horn dilation observed macroscopically correlated well w

107 nce of nontubal pathologies, such as uterine horn dilation, developed in mice following chlamydial in

108 alter the C. muridarum induction of uterine horn dilation.

109 lacement of over 50 skulls of the well-known horned dinosaur Triceratops within a stratigraphic frame

110 d intersegmental correlations in the ventral horns, dorsal horns, and central spinal cord gray matter

111 ow that multiple microcircuits in the dorsal horn encode this form of pain.

112 ilitate mechanical pain by inhibiting dorsal horn enkephalinergic/GABAergic interneurons.

113 circumference and the widths of the frontal horn (FH) and the corpus callosum (CC) were not signific

114 2 vector to rat cervical spinal cord ventral horn for targeting focal astrocyte GLT1 overexpression i

115 of horn polyphenisms by actively suppressing horn formation in low-nutrition males.

116 South American horned frogs (Ceratophrys) are a notable exception.

117 the superficial medullary and spinal dorsal horn from the trigeminal subnucleus caudalis to C2.

118 characterised by the separation of the hoof horn from the underlying skin.

119 al pain likely via modulation of deep dorsal horn GABAergic neurons.SIGNIFICANCE STATEMENT Pain is th

120 neurotransmission in the spinal cord dorsal horn gates nociceptive signaling, is essential in mainta

121 into the mouse uterus increased both uterine horn/glandular duct dilation and hydrosalpinx.

122 theless, the chlamydial induction of uterine horn/glandular duct dilation may be used to evaluate pla

123 as not required for the induction of uterine horn/glandular duct dilation.

124 n, horn length, and testes size, but not for horn growth or our measure of annual fitness.

125 nd leg length, parasite burden, horn length, horn growth, and testicular circumference.

126 population density for all traits apart from horn growth, with directional selection being stronger u

127 PV1-immunoreactive terminals, altered dorsal horn GRP immunoreactivity.

128 ion of these receptor subtypes in the dorsal horn has not been fully resolved.

129 inner part of lamina II (IIi ) of the dorsal horn, has been implicated in the expression of tactile a

130 erated cranial structures such as crests and horns, hereafter referred to collectively as ornaments,

131 or D1 in synaptic compartment (P3) in dorsal horn homogenates and presynaptic met-enkephalin-containi

132 mmunoreactivity for met-enkephalin in dorsal horn homogenates, which was dose-dependently attenuated

133 ons in the middle part of ipsilateral dorsal horn (iDH), along with significantly weaker activations

134 dolescence (postnatal day 25-30), the dorsal horn immune profile switches from an anti-inflammatory t

135 eptor and PKCgamma in the spinal cord dorsal horn (immunohistochemistry; Western blot) was upregulate

136 athway, a region of the sacral spinal dorsal horn important for the relay of pelvic visceral afferent

137 I but not lamina I of the spinal cord dorsal horn in nerve-injured versus control animals, suggesting

138 activated in astrocytes of the spinal dorsal horn in the SNL model.

139 uperficial laminae of the spinal cord dorsal horn in TOW mice, specifically in GABAergic inhibitory n

140 t C-fiber synapses in rat spinal cord dorsal horn in vivo.

141 s, and microglia activation in spinal dorsal horns in wild-type mice, but all these changes were comp

142 mmatory immune response in the spinal dorsal horn, infant nerve injury triggers an anti-inflammatory

143 ly in presynaptic Abeta-LTMRs removes dorsal horn inhibition that otherwise prevents Abeta-LTMR input

144 These results indicate that dorsal horn inhibitory synapses follow different rules of organ

145 ration underlies normalization of the dorsal horn inhibitory tone after injury and may be responsible

146 s" the gate by engaging a superficial dorsal horn interneuron that inhibits the firing of projection

147 st, it was proposed that a subset of lateral horn interneurons (LHNs), provide feed-forward inhibitio

148 hemys scripta elegans), we show that ventral horn interneurons in mid-thoracic spinal segments are fu

149 " circuits via excitatory superficial dorsal horn interneurons that express GRP and that likely targe

150 The deep dorsal horn is a poorly characterized spinal cord region implic

151 uggests that neuronal loss within the dorsal horn is involved in the development and/or maintenance o

152 ete population of neurons in the deep dorsal horn is required for mechanical pain and that activation

153 on neurons to a specific part of the lateral horn known to be involved in mediating avoidance.

154 profiles within the Vc/C2 superficial dorsal horn (lamina I) 3 weeks post-CCI-ION.

155 in central terminals innervating all dorsal horn laminae.

156 trade-off when investing in testes mass vs. horn length between the species.

157 We compared relative pronotal horn length using high-resolution X-ray CT scanning data

158 or body weight, leg length, parasite burden, horn length, and testes size, but not for horn growth or

159 dy weight, hind leg length, parasite burden, horn length, horn growth, and testicular circumference.

160 y are functionally integrated in the lateral horn (LH) of the vinegar fly, Drosophila melanogaster.

161 ronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ p

162 e dilated glandular ducts pushed the uterine horn lumen to closure or dilation and even broke through

163 tive hornless tortoise, unlike the Gondwanan horned meiolaniid radiation to the southwest.

164 toneurons, where it was required for ventral horn microglial activation and proliferation.

165 In the dorsal horn, most NECAB1/2 neurons are glutamatergic.

166 ed axonal and synaptic plasticity on ventral horn motor neurons.

167 ently in cortical layer V and spinal ventral horn, motor dysfunction, paralysis, and death.

168 al lamina I and in lamina IV/V of the dorsal horn (n = 5).

169 issecting the cellular composition of dorsal-horn networks, studies are beginning to elucidate the in

170 We found that when dorsal horn neurokinin 1 receptor-positive neurons or descendin

171 ors (GlyRs) play a role in control of dorsal horn neuron excitability, their relative contribution to

172 l and thermal hypersensitivity of rat dorsal horn neurones and enhanced perceptual responses of human

173 d as augmented evoked activity of rat dorsal horn neurones and increased perceptual responses of huma

174 Here we show that in spinal dorsal horn neurons >80% of mGluR5 is intracellular, of which a

175 Here we show that lateral horn neurons (LHNs) receive input from sparse and stereo

176 ptional changes in superficial spinal dorsal horn neurons (SSDHN) are essential in the development an

177 nslation, was activated in rat spinal dorsal horn neurons after repeated intrathecal morphine injecti

178 hown to be expressed in glutamatergic dorsal horn neurons and critical for dorsal horn development, i

179 We investigated the role of spinal dorsal horn neurons and descending circuitry in plasticity medi

180 that a novel SOC signal is present in dorsal horn neurons and may play an important role in pain tran

181 elopment, is expressed in nociceptive dorsal horn neurons and that its deletion results in the specif

182 ide cotransporter KCC2 in spinal cord dorsal horn neurons are a major contributor to the central disi

183 ts in the specific loss of excitatory dorsal horn neurons by apoptosis, without any effect on inhibit

184 hyperexcitability of nociceptive deep dorsal horn neurons by TNF-alpha largely depends on the formati

185 Importantly, wide dynamic-range dorsal horn neurons continued to faithfully encode A-nociceptiv

186 To characterize the subtypes of dorsal horn neurons engaged by dopamine signaling in the hypera

187 tory postsynaptic currents (EPSCs) of dorsal horn neurons evoked by dorsal root stimulation in spinal

188 tory postsynaptic currents (EPSCs) of dorsal horn neurons evoked by dorsal root stimulation.

189 of glycine-activated current in mouse dorsal horn neurons from spinal cord slices.

190 lds of lamina IV-V wide dynamic-range dorsal horn neurons in response to both A- and C-nociceptor sti

191 ssed in individual wide dynamic-range dorsal horn neurons is modulated by prostanergic descending con

192 d the frequency of miniature EPSCs in dorsal horn neurons of FK506-treated rats.

193 cordings from mechanonociceptive deep dorsal horn neurons of normal rats in vivo, we found that spina

194 extracellular recordings from lumbar dorsal horn neurons of the mouse in response to graded thermal

195 othing is known about how superficial dorsal horn neurons process sensory input from muscle versus sk

196 identity and function in spinal cord dorsal horn neurons remain elusive.

197 e excitatory postsynaptic currents in dorsal horn neurons that could be blocked by gabapentin.

198 in synapses, such as those on anterior motor horn neurons that integrate many complex neural inputs.

199 ity of second-order trigeminovascular dorsal horn neurons that receive peripheral input from the cran

200 elicited by puff NMDA application to dorsal horn neurons was also significantly greater in FK506-tre

201 ontaneous and miniature EPSCs in most dorsal horn neurons was profoundly increased in FK506-treated r

202 Dorsal horn neurons with stronger C-nociceptor input were affec

203 t terminals vs inhibitory synapses on dorsal horn neurons).

204 s of a subpopulation of glutamatergic dorsal horn neurons, abnormal sensory afferent innervations, an

205 induces ROS production in spinal cord dorsal horn neurons, an effect eliminated by ROS scavenger N-te

206 uli activate overlapping ensembles of dorsal horn neurons, and that stimulus type and intensity is en

207 d neurons, but not wide dynamic-range dorsal horn neurons, and why it may not be effective in all mig

208 as abundant expression in superficial dorsal horn neurons, but not in the DRG.

209 only about 5% of the normal number of dorsal horn neurons, mainly in lamina IV, below the level of le

210 o potentiates glycinergic synapses on dorsal horn neurons, suggesting that GlyR LTP is triggered duri

211 inal cord and oxidative DNA damage in dorsal horn neurons.

212 regulated kinase (ERK) in superficial dorsal horn neurons.

213 hyperexcitability of nociceptive deep horsal horn neurons.

214 g shift in GABA reversal potential of dorsal horn neurons.

215 release-activated Ca(2+) channels in dorsal horn neurons.

216 emonstrate that SOCs are expressed in dorsal horn neurons.

217 SOCs produced an excitatory action in dorsal horn neurons.

218 ergic input from primary afferents to dorsal horn neurons.

219 yperexcitability of these superficial dorsal horn neurons.

220 clude creation of new protected areas in the horn of Africa and Liberia, as well as improved connecti

221 Although the Horn of Africa region has successfully eliminated endemi

222 nge exemplified by Somalia, a country in the Horn of Africa region.

223 uniquely is most frequent in Arabia and the Horn of Africa, but is distributed much more widely, fro

224 We confirm the broad significance of the Horn of Africa, Guinean forests, coastal forests of East

225 inal cord neurons and the superficial dorsal horn of rat spinal cord slices.

226 ynapse on second-order neurons in the dorsal horn of subnucleus caudalis and cervical C1/C2 spinal co

227 Large numbers of neurons in the dorsal horn of the cervical spinal cord were labeled, especiall

228 was preferably expressed within the anterior horn of the gray matter, in both cervical and lumbar sec

229 nhanced loss of motor neurons in the ventral horn of the lumbar spinal cord.

230 neurotransmission in the superficial dorsal horn of the spinal cord is thought to contribute to chro

231 mediated synaptic transmission in the dorsal horn of the spinal cord, an area critically involved in

232 ere we report that in the superficial dorsal horn of the spinal cord, glycinergic synapses on inhibit

233 ly enhancement of pain signals in the dorsal horn of the spinal cord, we combined a nocebo heat pain

234 romotor cranial nerve nuclei and the ventral horn of the spinal cord.

235 the primary synaptic afferents in the dorsal horn of the spinal cord.

236 ulate incoming noxious stimuli in the dorsal horn of the spinal cord.

237 itially integrated in the superficial dorsal horn of the spinal cord.

238 but also in the intermediate zone and dorsal horn of the spinal gray matter.

239 pe was counted within the superficial dorsal horn of the Vc/C2 and the means from each rat were compa

240 sensory axons only in the spinal cord dorsal horn of treated animals.

241 xcitatory synapses in the superficial dorsal horn of Vc/C2 could lead to enhanced activation of nocic

242 s of motor neuron cell bodies in the ventral horn of WT mice by 3 mo of age.

243 We constructed finite element models of the horns of different rhinoceros beetle species to test whe

244 Each horn was strongly connected to the same horn on neighboring segments, but this connectivity redu

245 cleus of the amygdala and spinal cord dorsal horn only in mice with ongoing allodynia.

246 e, constitutive immune suppression of dorsal horn pain activity.

247 trait thresholds, such as those involved in horn polyphenisms and the corresponding origin of altern

248 ole in the nutrition-dependent regulation of horn polyphenisms by actively suppressing horn formation

249 f beetle horns, an evolutionary novelty, and horn polyphenisms, a highly derived form of environment-

250 A notable alkaloid in yellow horned poppy (G. flavum [GFL]) is the aporphine alkaloid

251 The horn presumably assembles onto the virion just before or

252 brain centers target a region of the lateral horn previously implicated in pheromone perception.

253 These are a cephalic horn resulting from an extreme modification of the clype

254 inity anomaly was advected south around Cape Horn, resulting in brief but significant impacts on coas

255 In all cases, one of the uterine horns revealed collection due to a hemivaginal septum an

256 mulate wells from a specific well pad in the Horn River Basin, British Columbia, where there is suffi

257 s upstream pathway in the spinal cord dorsal horn (SCDH).

258 postmortem tissues of the spinal cord dorsal horn (SDH) from HIV-1/acquired immunodeficiency syndrome

259 vation of ERK signaling in the spinal dorsal horn (SDH) is required selectively for histamine-induced

260 ity of neurons within the superficial dorsal horn (SDH) of the spinal cord is thought to underlie hei

261 Neurons in the superficial dorsal horn (SDH) of the spinal cord play an important role in

262 rs and their terminals in superficial dorsal horn (SDH; laminae I-II) constitute two separate subpopu

263 inuous fields of epidermal scales and intact horn sheaths capping the body armor.

264 cal properties of biomaterials such as hair, horn, skin, or bone are determined by the architecture o

265 pathic pain, central sensitization of dorsal horn spinothalamic tract (STT) neurons is a major underl

266 The horn structure may represent some adaption to the marine

267 The purified particles carry a novel slender horn structure projecting from the vertex opposite the t

268 products of genes 53 and 54, are part of the horn structure.

269 l, as in other species, into cervical dorsal horn, subnucleus caudalis, subnucleus interpolaris, subn

270 rcuits related to pain and SCS in the dorsal horn, supraspinal structures, and the Pain Matrix.

271 regulate glutamate release at the DRG-dorsal horn synapse.

272 ation of glutamate release at the DRG-dorsal horn synapse.

273 ansmission at spinal cord superficial dorsal horn synapses in a rat partial nerve-injury model of neu

274 A preferential ability of the dorsal horn synaptic network to amplify nociceptive input arisi

275 linked recessive Menkes disease or occipital horn syndrome.

276 gerated sexual traits (for example, antlers, horns, tail feathers, mandibles and dewlaps), show that

277 ers projected to deeper layers of the dorsal horn than did C fibers.

278 excitatory interneurons (INs) in the dorsal horn that are important for transmitting innocuous light

279 afferent terminals in the superficial dorsal horn that co-expressed the neuropeptide CGRP.

280 f neurons in lamina III and IV of the dorsal horn that coexpress PAX2, a transcription factor for GAB

281 amide and S1P formation in the spinal dorsal horn that corresponded with the engagement of S1P recept

282 ling of synaptic spines in the spinal dorsal horn, thereby orchestrating functional and structural pl

283 hb5) inhibit itch pathways within the dorsal horn; they may represent mediators between noxious and p

284 transferred to the mushroom body and lateral horn through dual pathways termed medial and lateral ant

285 tion of central terminal TRPV1 in the dorsal horn to chronic pain has not been investigated directly.

286 es move from medial to lateral in the dorsal horn to dorsomedial to ventrolateral in nTTD, whereas in

287 ly weakened the strength of the intrasegment horn-to-horn connectivity only on the injury side and in

288 ivity in the healthy adult rat spinal dorsal horn via activation of spinal 5-HT3 receptors (5-HT3Rs).

289 epresses synaptic input to the spinal dorsal horn, via the inhibition of voltage-gated calcium channe

290 Cavalpha2delta1 in Vc/C2 superficial dorsal horn was associated with increased excitatory synaptogen

291 For example, in sagittal sections the dorsal horn was significantly stiffer than the ventral horn.

292 Each horn was strongly connected to the same horn on neighbor

293 s differs from GABAA receptors in the dorsal horn, where different receptor stoichiometries underlie

294 innervated layers I, II, and V of the dorsal horn, where pain-sensory afferents terminate.

295 els expressed in nerves of the spinal dorsal horn, where their activation is believed to reduce trans

296 eurons in lamina IIi of the medullary dorsal horn, where they constitute 1/3 of total neurons.

297 citatory synaptic transmission in the dorsal horn, which contributes to pain hypersensitivity in chro

298 fect of inhibition of VL-PAG COX-1 on dorsal horn wide dynamic-range neurons evoked by C- vs. A-nocic

299 All horns within a single spinal segment were functionally c

300 cy MRI signal correlations between different horns within spinal cord gray matter, we found distinct