ライフサイエンスコーパス: VSG

1 VSG also reduces bone marrow adipose tissue, in part via

2 VSG did not alter total intestinal triglyceride levels o

3 VSG had a profound effect on the bone marrow niche, with

4 VSG in humans is a complex procedure and includes peri-o

5 VSG internalization results in decreased expression of a

6 VSG or sham surgery was performed in high-fat diet-fed m

7 VSG resulted in weight loss and shifts in the intestinal

8 VSG switching occurs by frequent homologous recombinatio

9 VSG transcripts and VSG coats become highly heterogeneou

10 VSG was performed on Long-Evans rats with diet-induced o

11 VSGs are exclusively expressed from subtelomeric express

12 VSGs are expressed exclusively from subtelomeric loci, a

13 VSGs are monoallelically expressed from subtelomeric exp

14 osoma brucei genome contains more than 1,000 VSG genes.

15 is parasite expresses only one of its ~2,000 VSG genes at a time are unknown.

16 ients underwent one of three treatments: (1) VSG plus routine intravenous peri-operative antibiotics

17 The matched cohort included 1111 VSG and 922 RYGB patients: 16% were younger than 40 year

18 ous peri-operative antibiotics (n = 12), (2) VSG with intravenous vancomycin chosen for its low intes

19 f the VSG family, no complete structure of a VSG has been reported.

20 VEX1 was sequestered by the active VSG and silencing of other VSGs failed when VEX1 was eit

21 SG alone is sufficient to silence the active VSG gene and directionally attenuate the ES by disruptor

22 The active VSG gene is in a Pol I-transcribed telomeric expression

23 The active VSG is transcribed from 1 of 15 polycistronic bloodstrea

24 The telomere downstream of the active VSG is transcribed into a long-noncoding RNA (TERRA), wh

25 x inheritance in association with the active-VSG.

26 ereas negative regulation primarily affected VSGs.

27 Positive regulation affected VSGs and nontelomeric pol-I-transcribed genes, whereas n

28 ayed decreased chromatin accessibility after VSG.

29 he improvements in glucose homeostasis after VSG.

30 re was no hyperplasia of the intestine after VSG, but the intestinal absorption of alimentary glucose

31 sm, are up-regulated in livers of mice after VSG while genes in inflammatory pathways are down-regula

32 D36 were upregulated in wild-type mice after VSG.

33 ng total bile acids are known to occur after VSG.

34 mparative studies on diabetes outcomes after VSG and RYGB.

35 t blood levels of ghrelin were reduced after VSG, but not after Roux-en-Y gastric bypass, based on en

36 flammatory pathways are down-regulated after VSG.

37 ant antigens derived from multiple ancestral VSG lineages, whereas in Trypanosoma brucei VSG have rec

38 GB increases intestinal glucose disposal and VSG delays glucose absorption; both contribute to observ

39 DNA hybrids, telomeric/subtelomeric DSBs and VSG switching frequency back to WT levels.

40 controls transcription of telomeric ESs and VSG antigenic switching in Trypanosoma brucei.

41 rom subtelomeric expression sites (ESs), and VSG switching exploits subtelomere plasticity.

42 o control telomere-linked VSG expression and VSG switching.

43 e dimensions of Trypanosoma brucei HpHbR and VSG have been determined by small-angle X-ray scattering

44 nk between the mitochondrial respiratome and VSG gene silencing in bloodstream form T. brucei.

45 gression, reduced the abundances of rRNA and VSG mRNA, and resulted in rapid cell death.

46 bly increased in rats that received RYGB and VSG compared with those that were pair-fed or fed ad lib

47 P1 play important roles in VSG switching and VSG silencing regulation, respectively.

48 VSG transcripts and VSG coats become highly heterogeneous when VEX proteins

49 egularly switches its major surface antigen, VSG, in the bloodstream of its mammalian host to evade t

50 egularly switches its major surface antigen, VSG, thereby evading the host's immune response.

51 egularly switches its major surface antigen, VSG, to evade the host immune responses.

52 gularly switching its major surface antigen, VSG, which is expressed exclusively from subtelomeric lo

53 Specific association between VSG transcription and replication timing reveals a model

54 The interplay between VSG-mediated effects on systemic metabolism and bone bio

55 Sequence diversity between VSGs facilitates escape of a subpopulation of trypanosom

56 Blocking VSG synthesis normally triggers a precise precytokinesis

57 s fundamental in Trypanosoma brucei for both VSG gene switching and for generating antigenic diversit

58 VSG lineages, whereas in Trypanosoma brucei VSG have recent origins, and ancestral gene lineages hav

59 the C-terminal domain of Trypanosoma brucei VSG plays a crucial role in facilitating exchange, we re

60 part by food restriction, and completely by VSG.

61 ry for the metabolic improvements induced by VSG surgery.

62 the beneficial metabolic effects induced by VSG.

63 ntly low enough to trigger a characteristic 'VSG synthesis block' cell-cycle checkpoint, as some cell

64 a critical density threshold of its cognate VSGs on the parasite surface.

65 attering to elucidate the first two complete VSG structures.

66 a Pol I-transcribed ES, as well as conserved VSG 3'UTR 16-mer sequences for the generation of functio

67 t changes in food intake relative to control VSG mice.

68 Thus, the VEX-complex controls VSG-exclusion, while CAF-1 sustains VEX-complex inherita

69 y switching to the expression of a different VSG gene.

70 nfection, suggesting that drugs that disrupt VSG monoallelic expression could be used to treat trypan

71 n of silent VSG expression sites, to disrupt VSG monoallelic expression, and to generate viable and h

72 ace VSG using a repertoire of ~2500 distinct VSG genes.

73 Mutational analysis of the ectopic VSG 3'UTR demonstrated the essentiality of a conserved 1

74 GPR119, and CD36, were stratified to either VSG or sham surgery before body weight, body composition

75 echanism for diversifying the genome-encoded VSG repertoire.

76 response, none of the interventions, except VSG, significantly improved glucose tolerance.

77 atively examining the diversity of expressed VSGs in any population of trypanosomes and monitored VSG

78 Each parasite expresses VSGs in a monoallelic fashion that is tightly regulated.

79 In fact, VSG corrected hepatic triglyceride dysregulation in CD36

80 In fact, VSG normalized the impairment in glucose tolerance and c

81 Following VSG, circulating granulocyte-colony stimulating factor (

82 inal microbial composition acutely following VSG.

83 intestinal microbiota composition following VSG prior to substantial weight loss.

84 ght loss and metabolic improvement following VSG.

85 rget influencing clinical outcomes following VSG.

86 , RYGB, and in postprandial states following VSG.

87 hat TbRAP1, a telomere protein essential for VSG silencing, suppresses VSG gene conversion-mediated s

88 by recombination, arguing against models for VSG switch initiation through direct generation of a DNA

89 from 1 of 15 polycistronic bloodstream-form VSG expression sites (ESs), which are controlled in a mu

90 mount of subtelomeric DSBs and more frequent VSG switching.

91 ent genomic locations showed that functional VSG levels could be produced from a gene 60 kb upstream

92 data to compare vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) with respect to

93 comes following vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB).

94 the effects of vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass surgeries for obesity.

95 pass (RYGB) and vertical sleeve gastrectomy (VSG) and to identify potential taste-related predictors

96 a mouse model, vertical sleeve gastrectomy (VSG) caused trabecular and cortical bone loss that was i

97 Vertical sleeve gastrectomy (VSG) has recently surpassed gastric bypass to become the

98 Vertical sleeve gastrectomy (VSG) involves the resection of ~ 80% of the stomach and

99 Vertical sleeve gastrectomy (VSG) is an effective therapeutic approach for obesity an

100 cial effects of vertical sleeve gastrectomy (VSG) on plasma lipid levels are weight independent.

101 ed weight gain: vertical sleeve gastrectomy (VSG) or food restriction.

102 Vertical sleeve gastrectomy (VSG) produces sustainable weight loss, remission of type

103 s, we performed vertical sleeve gastrectomy (VSG), a surgery with clinical efficacy very similar to t

104 ures, including vertical sleeve gastrectomy (VSG), and has been widely hypothesized to contribute to

105 edures, such as vertical sleeve gastrectomy (VSG), are at present the most effective therapy for the

106 ypass (RYGB) or vertical sleeve gastrectomy (VSG), are the most effective approaches to resolve type

107 bypass (RYGB), vertical sleeve gastrectomy (VSG), oral glucose administration, and type 1 diabetes m

108 rence following vertical sleeve gastrectomy (VSG).

109 comes following vertical sleeve gastrectomy (VSG).

110 using drug-selection pressure, we generated VSG double-expresser T. brucei lines, which have disrupt

111 the trypanosome surface following a genetic VSG switch, and show that full coat replacement requires

112 ycoprotein (VSG) coat from its large genomic VSG repertoire.

113 To be expressed, a given VSG gene must be located in one of 15 telomeric regions

114 lex sustaining variant surface glycoprotein (VSG) allelic exclusion and antigenic variation in Trypan

115 dense coat of variant surface glycoprotein (VSG) at the cell surface.

116 its protective Variant Surface Glycoprotein (VSG) coat by antigenic variation.

117 cing its dense variant surface glycoprotein (VSG) coat from its large genomic VSG repertoire.

118 s of different variant surface glycoprotein (VSG) coat genes.

119 nges its dense variant surface glycoprotein (VSG) coat to avoid elimination by the immune system of i

120 placement of a variant surface glycoprotein (VSG) coat.

121 changing their variant surface glycoprotein (VSG) coat.

122 ential coat of Variant Surface Glycoprotein (VSG) comprising approximately 10% total protein.

123 I transcribed variant surface glycoprotein (VSG) expression sites (ESs) of Trypanosoma brucei.

124 omere-proximal variant surface glycoprotein (VSG) expression sites (ESs), suggesting a role in contro

125 ximal silenced variant surface glycoprotein (VSG) expression sites and procyclin loci, indicating a d

126 eam, expresses variant surface glycoprotein (VSG) from 1 of 15 bloodstream expression sites (BESs) by

127 one telomeric variant surface glycoprotein (VSG) gene at a time, producing superabundant and switcha

128 ranscribes its variant surface glycoprotein (VSG) gene expression sites (ESs) in a monoallelic fashio

129 I)-transcribed variant surface glycoprotein (VSG) gene expression sites (ESs), which are monoallelica

130 sses involving Variant Surface Glycoprotein (VSG) gene rearrangements at subtelomeres.

131 3H proteins in variant surface glycoprotein (VSG) gene silencing.

132 e silencing of variant surface glycoprotein (VSG) genes found adjacent to telomeres in polycistronic

133 c exclusion of variant surface glycoprotein (VSG) genes is essential for African trypanosomes to evad

134 ss hundreds of variant surface glycoprotein (VSG) genes, but only one is expressed from a telomeric e

135 The variant surface glycoprotein (VSG) of African trypanosomes, for example, is sized for

136 lion copies of variant surface glycoprotein (VSG) that is expressed from a single VSG gene, drawn fro

137 urface antigen variant surface glycoprotein (VSG) to evade mammalian host immune responses at the blo

138 e antigen, the Variant Surface Glycoprotein (VSG), in a monoallelic manner.

139 expressing the variant surface glycoprotein (VSG), the key protein in antigenic variation, we investi

140 at comprises a variant surface glycoprotein (VSG).

141 ly immunogenic Variant Surface Glycoprotein (VSG).

142 c coat made of variant surface glycoprotein (VSG).

143 e monolayer of variant surface glycoprotein (VSG).

144 ation of their Variant Surface Glycoprotein (VSG).

145 terminant (the Variant Surface Glycoprotein, VSG gene) as well as TbORC1 binding sites.

146 ombination of Variant Surface Glycoproteins (VSG) genes, most of which reside in a subtelomeric repos

147 iation of the Variant Surface Glycoproteins (VSG) that coat parasites while they reside within mammal

148 monolayer of variant surface glycoproteins (VSG) that covers its cell surface.

149 n of distinct variant surface glycoproteins (VSGs) at extremely high density on the cell surface.

150 ed that as parasites enter the tsetse's gut, VSG molecules released from trypanosomes are internalize

151 However, VSG levels were not consistently low enough to trigger a

152 However, VSG mice exposed to antibiotics, regardless of their spe

153 propose that BRCA2 acts to maintain the huge VSG repository of T. brucei, and this function has neces

154 y confirmed and its potential involvement in VSG repression or switching has not been thoroughly inve

155 of TDP1 results in up to 40-90% reduction in VSG and rRNA transcripts and a concomitant increase in h

156 factor, TbTRF, also plays a critical role in VSG switching regulation, as a transient depletion of Tb

157 ing activity is critical for TbTRF's role in VSG switching regulation.

158 Using this approach, we demonstrate roles in VSG ES silencing for two histone chaperones.

159 ns TbTIF2 and TbRAP1 play important roles in VSG switching and VSG silencing regulation, respectively

160 ric double-strand breaks (DSBs) and increase VSG switching rate.

161 , although NUP-2 silencing does not increase VSG switching.

162 silent VSGs in both BF and PF, and increased VSG switching particularly through the in situ transcrip

163 ir antigenic variation, but causes increased VSG switching by recombination, arguing against models f

164 affinity also led to significantly increased VSG switching frequencies, indicating that the telomere

165 Further, NUP-1 depletion leads to increased VSG switching and therefore appears to have a role in co

166 of high-resolution structures of individual VSG domains, we employed small-angle X-ray scattering to

167 The strength of TbRAP1-mediated BES-linked VSG silencing is stronger in the PF cells than that in B

168 is also required to control telomere-linked VSG expression and VSG switching.

169 xpression of BF Expression Site (BES)-linked VSGs and silencing of metacyclic VSGs (mVSGs) in BF cell

170 e previously shown that silencing BES-linked VSGs in BF cells depends on TbRAP1.

171 eats and immediately downstream of ES-linked VSGs in RNase H defective cells, which also have an incr

172 Besides inducing significant weight loss, VSG also improves glucose tolerance.

173 a central role for chromatin in maintaining VSG ES silencing.

174 tments proved to be detrimental to metabolic VSG outcomes, regardless of antimicrobial specificity of

175 BES)-linked VSGs and silencing of metacyclic VSGs (mVSGs) in BF cells are essential for antigenic var

176 te viable and healthy parasites with a mixed VSG coat.

177 any population of trypanosomes and monitored VSG population dynamics in vivo.

178 Monoallelic VSG transcription resumes after reexpression of TbPIP5K;

179 pletion of TbTRF leads to significantly more VSG switching events.

180 nfected with these parasites mounted a multi-VSG antibody response, which rapidly reduced parasitemia

181 The consequences of exposing multiple VSGs during an infection, in terms of antibody response

182 shows that simultaneous exposure of multiple VSGs is highly detrimental to the parasite, even at the

183 and tested in Long Evans male rats, namely: VSG, Fundal (F)-Resection, Gastric Sleeve Plication (GSP

184 ed with greater weight loss in RYGB, but not VSG.

185 eover, in the absence of FXR, the ability of VSG to reduce body weight and improve glucose tolerance

186 rtunities, as well as considering aspects of VSG biology that remain to be fully explored.

187 hanisms underlying the metabolic benefits of VSG have remained elusive.

188 tein complex and functions in the control of VSG allelic exclusion.

189 e been examined extensively, the dynamics of VSG coat replacement at the protein level, and the impac

190 However, the dynamics of VSG expression in T. brucei during an infection are poor

191 underlying mechanism of the effectiveness of VSG.

192 We compared the effects of VSG in ghrelin-deficient mice and wild-type mice on food

193 SF was found to recapitulate many effects of VSG on bone and the marrow niche.

194 Effects of VSG on induction of neutrophils and depletion of marrow

195 SF plays an intermediary role for effects of VSG on the bone marrow niche.

196 t appear to be required for these effects of VSG.

197 Hence, allelic exclusion of VSG genes may entail control of nuclear phosphoinositide

198 in restricting the monoallelic expression of VSG.

199 s to macronutrient preference independent of VSG, while removal of CD36 signaling blunts the VSG-indu

200 DSB formation, which is a strong inducer of VSG switching.

201 ors mediating these extremely high levels of VSG expression by inserting ectopic VSG117 into VSG221 e

202 s for the generation of functional levels of VSG expression in bloodstream form T. brucei.

203 Single-molecule diffusion measurements of VSG in supported lipid bilayers substantiate this possib

204 tial species differences in the mechanism of VSG diversification.

205 Here we evaluate the rate of VSG replacement at the trypanosome surface following a g

206 We therefore examined the results of VSG surgery applied to mice with diet-induced obesity an

207 A breaks, including in the telomeric site of VSG expression.

208 e biosynthesis, trafficking, and turnover of VSG, emphasising those unusual mechanisms that act to ma

209 we demonstrate that the therapeutic value of VSG does not result from mechanical restriction imposed

210 loped a method, based on de novo assembly of VSGs, for quantitatively examining the diversity of expr

211 urprising insight that a broad repertoire of VSGs is rapidly expressed.

212 ion results in simultaneous transcription of VSGs from all telomeric expression sites (ESs) and from

213 actome analyses indicated that the impact on VSG silencing was indirect, while the ZC3H39/40 complex

214 ontributes to its strong silencing effect on VSGs.

215 They transcribe only one VSG gene at a time from 1 of about 20 telomeric expressi

216 ne ES is fully active at a time, so only one VSG gene is transcribed per cell.

217 icantly better in rats that received RYGB or VSG compared with rats fed ad lib or pair-fed, whereas g

218 fter a meal among rats that received RYGB or VSG.

219 red by the active VSG and silencing of other VSGs failed when VEX1 was either ectopically expressed o

220 Our results demonstrate how past VSG evolution indirectly determines the ability of conte

221 Rather, VSG is associated with increased circulating bile acids,

222 In obese rats, VSG is as effective as RYGB for increasing secretion of

223 Rats that received VSG had a marked, weight-independent reduction in secret

224 We reconstruct VSG diversification showing that Trypanosoma congolense

225 proteins play important roles in regulating VSG silencing and switching.

226 While the mechanisms regulating VSG gene expression and diversification have been examin

227 G mRNA appears to have a role in restricting VSG expression to a single gene.

228 The mechanism(s) restricting VSG expression to a single BES are not well understood.

229 Unlike food restriction, VSG corrected the effect of hepatocyte p53 ablation to l

230 Obese male rats underwent RYGB, VSG, or sham (control) operations.

231 We found that the expression of a second VSG alone is sufficient to silence the active VSG gene a

232 s sufficient to open the chromatin of silent VSG expression sites, to disrupt VSG monoallelic express

233 enriched at the active compared with silent VSG ES and immediately downstream of ribosomal DNA promo

234 ed in derepression of telomere-linked silent VSGs in both BF and PF, and increased VSG switching part

235 rotein (VSG) that is expressed from a single VSG gene, drawn from a large repertoire and located near

236 incomplete, however, allowing G2/M-specific VSG ES derepression following knockdown of histone H3.

237 ut has the opposite effect at a subtelomeric VSG.

238 manner and sustain the active, subtelomeric VSG-associated transcription compartment.

239 RAP1 silencing of telomeric and subtelomeric VSG genes.

240 ion sites (ESs) and from silent subtelomeric VSG arrays.

241 al recombination, it suppressed subtelomeric VSG recombination, and these locus-specific effects were

242 s significantly stronger at the subtelomeric VSG loci than at chromosome internal loci.

243 tein essential for VSG silencing, suppresses VSG gene conversion-mediated switching.

244 asite varies this highly immunogenic surface VSG using a repertoire of ~2500 distinct VSG genes.

245 hly flexible overall topology of the surface VSG coat, which displays both lateral movement in the pl

246 time, producing superabundant and switchable VSG coats.

247 lusion-1 (VEX1) protein binds both telomeric VSG-associated chromatin and VEX2, an ortholog of nonsen

248 some depletion and derepression of telomeric VSG ESs.

249 cated in one of 15 telomeric regions termed "VSG expression sites" (ESs), each of which contains a po

250 ression site-associated genes and a terminal VSG gene.

251 %) lower total diabetes medication dose than VSG by the second half of postoperative year 2.

252 aling the receptor to be more elongated than VSG.

253 eduction and gastric volume, confirming that VSG is the only effective long-term weight loss strategy

254 We found that VSG produced comparable outcomes in each strain.

255 We found that VSG reduced body mass and improved both glucose and lipi

256 We found that VSG-operated GLP-1 receptor-deficient mice responded sim

257 We demonstrate here that VSG in C57BL/6J wild-type male mice can reverse these ch

258 Our results indicate that VSG induces global regulatory changes that impact hepati

259 teins is a novel function and indicates that VSG serves a dual role in trypanosome biology-that of fa

260 this issue of the JCI, Li et al. report that VSG rapidly reduces bone mass, as observed in humans, vi

261 Here, the authors show that VSG replacement takes several days to complete, and the

262 expenditure and body weight and suggest that VSG can improve alterations in energetics associated wit

263 ibility between domains, which suggests that VSGs can adopt two main conformations to respond to obst

264 The VSG-exclusion-1 (VEX1) protein binds both telomeric VSG-

265 likely that the receptor protrudes above the VSG layer and unlikely that the VSG coat can prevent imm

266 ted where it is readily accessible above the VSG layer.

267 f the interventions were as effective as the VSG.

268 , while removal of CD36 signaling blunts the VSG-induced shift toward carbohydrate preference.

269 Bs inefficiently direct recombination in the VSG expression site.

270 nderpinning synthesis and maintenance of the VSG coat.

271 Despite the importance of the VSG family, no complete structure of a VSG has been repo

272 een telomeric ESs or by recombination of the VSG gene expressed.

273 ter that is located 45-60 kb upstream of the VSG gene.

274 nderstand the receptor in the context of the VSG layer, the dimensions of Trypanosoma brucei HpHbR an

275 ption initiation and that, surprisingly, the VSG mRNA appears to have a role in restricting VSG expre

276 er, most of the resultant cells switched the VSG gene expressed.

277 es above the VSG layer and unlikely that the VSG coat can prevent immunoglobulin binding to the recep

278 virulence of African trypanosomes, where the VSG coat is used to evade the host immune system.

279 obin-hemoglobin receptor (HpHbR) within this VSG coat mediates heme acquisition.

280 rapid internalization of antibodies bound to VSG on the surface of the trypanosome is blocked.

281 Diet-induced obese mice were randomized to VSG or sham surgery, with or without exposure to antibio

282 ucose tolerance were improved in response to VSG in PPARalphaKO, GPR119KO, and CD36KO mice.

283 ood restricted to match their body weight to VSG-operated mice.

284 ion dynamics, we reveal that the transcribed VSG expression site is the only telomeric site that is e

285 We identified trypanosome VSG exclusion-1 (VEX1) using a genetic screen for defect

286 to identify adults with diabetes undergoing VSG or RYGB in 2010 to 2016.

287 Only patients undergoing VSG with routine peri-operative antibiotics showed a sig

288 me off all medications than those undergoing VSG.

289 lelic expression of the antigenically varied VSG is disrupted.

290 n plays little role in diversifying T. vivax VSG sequences.

291 ndividuals or animals that underwent RYGB vs VSG.

292 The intestine adapts differently to RYGB vs VSG.

293 om subtelomeric expression sites (ESs) where VSG genes are flanked by upstream 70 bp repeats and down

294 vivax is a related, livestock pathogen whose VSG lack structures that facilitate gene conversion in T

295 Here we show that species-wide VSG repertoire is broadly conserved across diverse T. vi

296 h not a primary mechanism for bone loss with VSG, G-CSF plays an intermediary role for effects of VSG

297 patients were more likely than patients with VSG to come off all diabetes medications up to 2 years a

298 Patients with VSG were less likely than matched RYGB patients to disco

299 ry for the metabolic improvements shown with VSG, but also suggest an interesting role for apoA-IV in

300 cycle-specific chromatin remodelling within VSG ESs.