ライフサイエンスコーパス: AAA

1 AAA cases and interventions were identified from claims

2 AAA growth was recorded at 12 months.

3 AAA+ ATPase ClpB is a promising target for the developme

4 AAA+ proteases are degradation machines that use ATP hyd

5 AAA+ proteases perform regulated protein degradation in

6 AAA+ proteins have key functionalities encompassing unfo

7 AAAs were generated in Sprague-Dawley rats by exposing t

8 AAAs, which eventually ruptured, demonstrated a signific

9 A separate 192 AAA patients with serial CT scans during AAA surveillanc

10 We observed that 19 of 24 AAA risk variants associate with aneurysms in at least 1

11 d tomography angiography (CTA) data from 258 AAA patients, the lumen of the aneurysmal neck was analy

12 s) DNA are bound within the C-tier of MCM2-7 AAA+ ATPase domains.

13 ing compartmentalized peptidase (ClpP) and a AAA+ unfoldase (ClpX or ClpA/ClpC).

14 neously modulate the catalytic activity of a AAA+ enzyme, efficiently promote recognition of some sub

15 rom mouse models expressing phospho-ablated (AAA) and phosphomimetic (DDD) cMyBP-C as well as control

16 ining protein or Cdc48, is a highly abundant AAA+ engine that fuels diverse energy-consuming processe

17 a of aromatic amino acids and nucleic acids (AAA + NA), tryptophan residues, nicotinamide adenine din

18 motor domain of dynein contains three active AAA+ ATPases (AAA1, 3, and 4), only the functions of AAA

19 associated with various cellular activities (AAA(+)) superfamily of proteins.

20 associated with diverse cellular activities (AAA+ proteins) are macromolecular machines that convert

21 associated with diverse cellular activities (AAA+ proteins) termed Rubisco activases (Rcas).

22 ciated with the diverse cellular activities (AAA+) protein, N-ethylmaleimide-sensitive factor (NSF/Se

23 d by ILT; (iii) reduced in circulation after AAA surgery; (iv) differs between fast and slow growth A

24 e molecular magnetic resonance imaging in an AAA mouse model.

25 Since Yta7(ATAD2) is an AAA(+) ATPase and potential hexameric unfoldase, our res

26 Cytoplasmic dynein is an AAA(+) motor that drives the transport of many intracell

27 served nonstructural protein 2C, which is an AAA+ ATPase, is a promising target for drug development.

28 Geometric features of an AAA can predict its future growth.

29 LAP1 binds to and activates torsinA, an AAA+ ATPase that resides in the perinuclear space and co

30 strains expressing protein variants with an AAA motif instead of EAL are delayed in development, sim

31 FtsH, a bacterial membrane-anchored AAA+ protease, plays a vital role in membrane protein qu

32 7 studies per person-year open; P<0.001) and AAA-related reinterventions (4.0 per 100 person-years EV

33 hat TFEB protects against VSMC apoptosis and AAA.

34 Using Attractin and AAA diameter as input variables, the AUROC for predictin

35 found between periopathogens such as Pg and AAA diameters and volumes, but no difference could be ev

36 we find significant reductions of plasma and AAA lesion IL6 expression in Apoe(-/-) Ige(-/-) mice.

37 pregulated MMP in abdominal aortic aneurysm (AAA) and, hence, MMP-12-targeted imaging may predict AAA

38 r contribution to abdominal aortic aneurysm (AAA) formation and development, we determined the freque

39 Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, leukocy

40 Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with an up t

41 Abdominal aortic aneurysm (AAA) is a severe aortic disease with a high mortality ra

42 Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality;

43 ion to operate on abdominal aortic aneurysm (AAA) is primarily on the basis of measurement of maximal

44 important role in abdominal aortic aneurysm (AAA) pathogenesis, with effects on disease progression a

45 Abdominal aortic aneurysm (AAA) remains a fatal disease.

46 c clamping during abdominal aortic aneurysm (AAA) repair results in ischemia-reperfusion injury (IRI)

47 n open juxtarenal abdominal aortic aneurysm (AAA) repair, the volume effect in these difficult operat

48 equiring elective abdominal aortic aneurysm (AAA) repair.

49 d with rupture of abdominal aortic aneurysm (AAA), an age-related vascular disease.

50 iodontitis and of abdominal aortic aneurysm (AAA).

51 seases, including abdominal aortic aneurysm (AAA).

52 tment outcomes of abdominal aortic aneurysm (AAA).

53 k factor of human abdominal aortic aneurysm (AAA).

54 tures for future abdominal aortic aneurysms (AAA) growth prediction.

55 sk of developing abdominal aortic aneurysms (AAA).

56 the treatment of abdominal aortic aneurysms (AAAs) are being increasingly used worldwide.

57 Ruptured abdominal aortic aneurysms (AAAs) have mortality estimated at 81%.

58 for asymptomatic abdominal aortic aneurysms (AAAs) with a diameter of at least 55 mm for men and 50 m

59 0.001) significantly correlated with annual AAA growth.

60 ns between the lid subunit Rpn5 and the base AAA+ ATPase ring are important for stabilizing the subst

61 model of impaired inducible autophagy (Bcl2(AAA) ).

62 thesis rates and basal autophagy in the Bcl2(AAA) mice, while acute exercise activated BNIP3 and Park

63 alcium release yielded no difference between AAA/DDD and controls in calcium content of the sarcoplas

64 deficiency in Apoe(-/-) Ige(-/-) mice blunts AAA growth and reduces lesion accumulation of macrophage

65 aplegia protein M1 Spastin, a membrane-bound AAA ATPase found on LDs, coordinates fatty acid (FA) tra

66 The mitochondrial membrane-bound AAA protein Bcs1 translocate substrates across the mitoc

67 tor proteins modulate substrate selection by AAA+ proteases.

68 y either group did not significantly change (AAA SUV=0.86+/-0.17 and sham-control SUV=0.46+/-0.10), i

69 isk and a week-by-week study to characterize AAA development.

70 pore loop-substrate contacts spans both ClpA AAA+ domains.

71 an ATP-dependent protease in which the ClpX AAA+ motor binds, unfolds, and translocates specific pro

72 We show that the conserved AAA-ATPase PCH-2/TRIP13, which remodels the checkpoint e

73 nkyrin-repeat domain combines with conserved AAA+ elements to enable stand-alone disaggregase activit

74 previous characterizations of the cytosolic AAA+ domain in vitro had proved challenging due to its m

75 The latter value is typical of DDD-AAA H-bond dimers, consistent with proton transfer acros

76 Over the past decades AAA repair underwent substantial changes, that is, the i

77 R2 receptor blocking significantly decreased AAA uptake (SUV=0.42+/-0.09).

78 dy including primary repairs of degenerative AAAs in the Netherlands between 2016 and 2018 in which t

79 ntain one delta, three gamma, and one delta' AAA+ subunits semi-circularly arranged in the order delt

80 ting inhibition of a conserved Dictyostelium AAA ATPase, p97, a homolog of the human transitional end

81 otential source of systemic mediators during AAA progression.

82 neutrophil transendothelial migration during AAA formation.

83 192 AAA patients with serial CT scans during AAA surveillance were identified from an ongoing clinica

84 follow-up and should be avoided in elective AAA cases.

85 Changes in elective AAA management reduced short-term mortality, but failed

86 tions about which approach to offer elective AAA patients should not be based on relative cost.

87 All patients undergoing elective AAA repair between 2013 and 2016 registered in the Dutch

88 (82.7% male) patients who underwent elective AAA repair between 2001 and 2015 in Sweden.

89 a large conformational change in the entire AAA+ domain that leads the HD to form both heptamer and

90 Msp1 is a conserved eukaryotic AAA+ ATPase localized to the outer mitochondrial membran

91 ented using an automated pipeline to extract AAA diameter (APD), undulation index (UI) and radius of

92 ergent optimization toward the ATPase family AAA domain containing 2 (ATAD2) and cat eye syndrome chr

93 d molecular mechanisms governing McrB family AAA + motors.

94 Therefore, novel biomarkers for AAA characterization are needed.

95 These are novel biomarkers for AAA growth prediction in humans.

96 cs pipeline to discover novel biomarkers for AAA growth prediction.

97 enopause may be an important risk factor for AAA in women with significant smoking history.

98 veals an additional regulatory mechanism for AAA+ ATPases.

99 activity was the most accurate predictor for AAA rupture (sensitivity 80%, specificity 100%, area und

100 years, many of the key elements required for AAA+ activity have been identified through genetic, bioc

101 te certainty that the harms of screening for AAA in women aged 65 to 75 years who have never smoked a

102 STF recommends against routine screening for AAA with ultrasonography in women who have never smoked

103 naling as a potential therapeutic target for AAA progression.

104 For AAAs smaller than 50 mm, a regression model that include

105 mances were assessed in both cohorts and for AAAs smaller than 50 mm by using area under the receiver

106 were trained and optimized to predict future AAA growth in these patients.

107 tractin correlates significantly with future AAA growth (Spearman r = 0.35, P < 0.005).

108 y; (iv) differs between fast and slow growth AAAs.

109 arkers for abdominal aortic aneurysm growth (AAA) prediction.

110 Hsp104 is a hexameric AAA(+) ring translocase, which drives protein disaggrega

111 gation, we have explored Hsp104, a hexameric AAA+ protein disaggregase from yeast.

112 degradation machine consists of a hexameric AAA+ unfoldase (ClpX) and a pair of heptameric serine pr

113 kingdoms of life and consist of a hexameric AAA+ unfoldase/translocase in complex with a self-compar

114 pathologic characterization of rat and human AAA tissues obtained from surgery revealed increased exp

115 y described as inhibitor leads for the human AAA+ ATPase p97, an antitumor target.

116 he role of VSMC TFEB and a TFEB activator in AAA in vivo.

117 ses in both spontaneous aftercontractions in AAA cardiomyocytes and the incidence of arrhythmias in v

118 ay represent a novel therapeutic approach in AAA management.

119 The impact of changes in AAA management was established by a time-resolved analys

120 hil chemoattractants MIP-2alpha and CXCL5 in AAA lesions or macrophages from Apoe(-/-) Ige(-/-) mice,

121 RPV4(-/-) mice had a significant decrease in AAA formation, aortic inflammation, and vascular remodel

122 ing proteins were significantly decreased in AAA hearts compared with controls.

123 pic drug, rescued the contractile deficit in AAA cardiomyocytes, but not the calcium-handling abnorma

124 autoradiography was significantly higher in AAA compared to normal aortic regions.

125 This study supports a direct role of IgE in AAA by promoting lesion chemokine expression, inflammato

126 their target genes focusing on their role in AAA.

127 The localization of radiotracer uptake in AAA was verified with high-resolution computed tomograph

128 rk implicated intraluminal thrombus (ILT) in AAAs to be a potential source of systemic mediators duri

129 Tracer uptake in AAAs that subsequently ruptured (SUV=1.31+/-0.14; P<0.00

130 ogression of angiotensin II (Ang II)-induced AAA by facilitating reactive oxygen species (ROS) format

131 sion- and peri-aortic CaCl(2) injury-induced AAA in mice.

132 Pharmacological therapy is needed to inhibit AAA expansion and prevent aneurysm rupture.

133 bility of drugs, activates TFEB and inhibits AAA formation and progression in mice.

134 t 2-hydroxypropyl-beta-cyclodextrin inhibits AAA in a VSMC TFEB-dependent manner in mouse models.

135 Initial AAA characteristics of the derivation cohort were analyz

136 onenhancing thrombus area compared to intact AAAs (p = 0.001).

137 data of the cases with clinically irrelevant AAA diameter enlargement were evaluated.

138 open AAA repairs, and total open juxtarenal AAA repairs.

139 Using the novel PlxnA4(KRK-AAA) knock-in male and female mice, generated by CRISPR/

140 rotein (RIME) assay, we identified RuvB-like AAA ATPase 1 (RUVBL1/Pontin) and enhancer of rudimentary

141 Many AAA+ proteases and protein-remodeling motors are likely

142 is dependent on the conserved inner-membrane AAA+ ATPase/protease, FtsH.

143 Here, we establish that a mitochondrial AAA+ protein, Skd3 (human ClpB), couples ATP hydrolysis

144 The mitochondrial AAA ATPase Msp1 is well known for extraction of mislocal

145 previously discovered that the mitochondrial AAA+ protein unfoldase ClpX (mtClpX) activates the initi

146 ce, identifying specific eoxPL that modulate AAA.

147 at can regulate vascular tone, in modulating AAA formation.

148 Studies of human and mouse AAA tissue reveal expanded populations of macrophages pr

149 ctive Tfeb knockout mice and different mouse AAA models, we determined the role of VSMC TFEB and a TF

150 nd promotes AAA formation in different mouse AAA models.

151 2.2- angstrom crystal structure of the MoxR AAA+ protein CbbQ2 from Acidithiobacillus ferrooxidans r

152 ity and crosstalk among the motor's multiple AAA+ domains.

153 dent prediction of risk of rupture in murine AAA.

154 osen as the lead tracer and tested in murine AAA.

155 ssessment of vascular permeability in murine AAAs and prediction of rupture risk.

156 ated uptake nearly twice that of nonruptured AAAs (SUV=0.73+/-0.11).

157 We identify novel AAA genetic associations with therapeutic implications a

158 biomarker for the noninvasive assessment of AAA inflammation that may aid in associated rupture pred

159 We examined the association of AAA risk variants with aneurysms in the lower extremity,

160 Novel biomarker of AAA growth is a recognised priority in research.

161 7C/A SNPs may serve as genetic biomarkers of AAA incidence.

162 ek-by-week study for the characterization of AAA development with imaging after 1, 2, 3 and 4 weeks.

163 ial to enable individual characterization of AAA.

164 d high-resolution structure determination of AAA+ proteins trapped in the act of processing substrate

165 uscle cell (VSMC) TFEB in the development of AAA and establish TFEB as a novel target to treat AAA.

166 ts of Notch deficiency on the development of AAA by reduction of infiltrating myeloid cells.

167 profound long-term survival disadvantage of AAA patients.

168 tified risk loci explain a small fraction of AAA heritability.

169 for predicting no growth and fast growth of AAA at 12 months is 85% and 76%, respectively.

170 ases mediators during the natural history of AAA growth.

171 e never smoked and have no family history of AAA outweigh the benefits.

172 e never smoked and have no family history of AAA.

173 ury (ALI) to mice doubles their incidence of AAA and accelerates macrophage-driven proteolytic damage

174 t extent these changes improved longevity of AAA patients.

175 The elastase-treatment model of AAA in C57BL6 (WT) mice and Angiotensin II treatment mod

176 In this study, we used a mouse model of AAA to investigate the potential of magnetic resonance i

177 d inflammatory activity in a murine model of AAA.

178 sal of the basis for the excess mortality of AAA patients.

179 Novel methods for growth prediction of AAA are recognised as a research priority.

180 sm rupture, but not examined as predictor of AAA growth.

181 opause was associated with increased risk of AAA [hazard ratio 1.37 (1.14, 1.66)], but the associatio

182 tion between premature menopause and risk of AAA amongst women who have never smoked.

183 e menopause and early menarche, with risk of AAA in a large, ethnically diverse cohort of women.

184 e, which was associated with greater risk of AAA in all models [hazard ratio 1.63 (1.24, 2.23)].

185 ed with at least an 8-fold increased risk of AAA incidence (p < 0.001).

186 iation between polymorphisms and the risk of AAA incidence.

187 n at significantly increased genetic risk of AAA independent of family history.

188 and were associated with a decreased risk of AAA occurrence (p < 0.001 and p = 0.0012, respectively).

189 lable biomarkers fail to predict the risk of AAA rupture independent of aneurysm size.

190 he was not associated with increased risk of AAA.

191 s between periodontitis severity and size of AAA.

192 we review how substrate-bound structures of AAA+ proteins have expanded our understanding of ATP-dri

193 strategy for the prevention and treatment of AAA.

194 models used for mechanistic understanding of AAA.

195 We show that ILT of AAAs releases mediators during the natural history of AA

196 mine the causal effects of blood pressure on AAA.

197 To design macrocycles with one (AAA), two (AAB), or three (ABC) different carbazole unit

198 Complex open AAA repairs should be performed at experienced centers,

199 for patients undergoing elective EVR or open AAA repair from 2004 to 2015.

200 pital's average annual volume for total open AAA repairs, and total open juxtarenal AAA repairs.

201 Of 8880 total open AAA repairs, there were 3470 open juxtarenal cases.

202 , open juxtarenal volume, but not total open AAA volume was associated with perioperative mortality (

203 Quality Initiative (VQI) who underwent open AAA repair from 2003 to 2016.

204 modeling, we created OPG knock-in mice (opg (AAA) ).

205 Surprisingly, opg (AAA/AAA) mice displayed a severe osteoporotic phenotype

206 otic phenotype with similar severity to opg (AAA/AAA) mice.

207 tures revealed dynamic movements of the ORC1 AAA+ and ORC2 winged-helix domains that likely impact DN

208 chitectural principles established for other AAA proteins yet specializes Msp1 for its unique role in

209 f substrate translocation proposed for other AAA+ ATPases (adenosine triphosphatases).

210 in the axial channel, as observed for other AAA+ proteases and protein-remodeling machines.

211 red from these structural features for other AAA+ unfoldases, but biochemical and single-molecule bio

212 Many other AAA+ proteins function by threading macromolecules throu

213 amma/delta' hydroxyl group that 99% of other AAA+ proteins lack.

214 Akin to other AAA proteins, Msp1 forms hexameric spirals that transloc

215 esting to identify those with high polygenic AAA risk, once the cost of genotyping becomes comparable

216 At day 7 post-AAA induction, the radiotracer uptake (standardized upta

217 At 14 days post-AAA induction, radiotracer uptake by either group did no

218 , hence, MMP-12-targeted imaging may predict AAA progression and rupture risk.

219 ational fluid dynamics parameters to predict AAAs that are likely to progress in size.

220 size of nonenhancing-thrombus-area predicted AAA rupture with high sensitivity/specificity (100%/86%)

221 ciency increases VSMC apoptosis and promotes AAA formation in different mouse AAA models.

222 Relative survival was used to quantify AAA-associated mortality, and to adjust for changes in l

223 Rat AAA rupture was stimulated by the administration of beta

224 Thus, procoagulant PL regulate AAA development through complex interactions with clotti

225 oxidized phospholipids (eoxPL) in regulating AAA.

226 tion, surveillance imaging, reinterventions (AAA-related and abdominal wall procedures), and all-caus

227 s - katanin, spastin, fidgetin - are related AAA-ATPases that cut microtubules into shorter filaments

228 hy (CT) scans from patients with infra-renal AAAs were analysed.

229 structure resembles other recently reported AAA unfoldases, including the meiotic clade relative Vps

230 Protein quality control pathways require AAA+ proteases, such as Clp and Lon.

231 ClpA is a hexameric double-ring AAA+ unfoldase/translocase that functions with the ClpP

232 45 (48%) required intervention for ruptured AAA.

233 RUVBL1 and RUVBL2 AAA-ATPases form an hetero-hexameric ring that is part o

234 ionarily conserved microtubule (MT)-severing AAA-ATPase enzyme Katanin is emerging as a critical regu

235 inging the total number of known significant AAA loci to 24.

236 The GTP-specific AAA + protein McrB powers translocation along DNA and it

237 ectional study compared patients with stable AAA (n = 30) and patients with unstable AAA (n = 31) bas

238 to lyse arterial matrix, thereby stimulating AAA.

239 ClpXP is one of the most thoroughly studied AAA+ proteases, but relatively little is known about the

240 massive (>500 kDa) protein has an N-terminal AAA (ATPase associated with diverse cellular activities)

241 ata add to the growing body of evidence that AAA+ molecular machines generate translocating forces by

242 rescent staining and FACS analysis show that AAA lesion neutrophils express FcepsilonR1.

243 The AAA ATPase katanin severs microtubules.

244 The AAA protein Msp1 extracts mislocalized tail-anchored mem

245 The AAA ring is followed by large (>2,000 aa) linking domain

246 The AAA(+) ATPase and bromodomain factor ATAD2/ANCCA is over

247 The AAA+ ATPase, p97, also referred to as VCP, plays an esse

248 The AAA+ protein disaggregase, Hsp104, increases fitness und

249 te protein, which directs degradation by the AAA+ ClpXP protease.

250 tial proteostatic functions performed by the AAA+ superfamily of protein molecular machines.

251 mitochondrial inner membrane, comprising the AAA+ protease, LonP1, and subunits of oxidative phosphor

252 In nonmetazoan eukaryotes, the AAA+ disaggregase Hsp78 resolubilizes and reactivates pr

253 0 and serves as a recruitment signal for the AAA-ATPase Cdc48/p97, which actively disassembles the co

254 tivity, although some flexibility in how the AAA+ ring docks with ClpP may be necessary for optimal f

255 ateral or anterior/posterior symmetry of the AAA was identified.

256 eted ORC5, the protein would lack 80% of the AAA+ ATPase domain, including the Walker A motif.

257 Many members of the AAA+ ATPase family function as hexamers that unfold thei

258 Signaling is attenuated by a homolog of the AAA+ ATPase Pch2/TRIP13, which binds and disassembles th

259 led onto DNA by a clamp loader ATPase of the AAA+ family.

260 nit N terminus through the axial pore of the AAA+ hexamer.

261 sm underlies the functional diversity of the AAA+ superfamily were uncertain.

262 lecular docking of the MIDAS domain onto the AAA ring is required for Mdn1 to transmit force to its r

263 A disordered region outside the AAA core anchors katanin to the microtubule while the AA

264 y, and native mass spectrometry to study the AAA and MIDAS domains separately or in combination.

265 , recent publications have proposed that the AAA+ unfoldases ClpA and ClpX rotate with respect to the

266 ay, or why tethering the MIDAS domain to the AAA ring is required for protein function.

267 Free MIDAS domain can bind to the AAA ring of this construct in a stereo-specific bimolecu

268 Hence, tethering the MIDAS domain to the AAA ring serves to prevent, rather than promote, MIDAS d

269 ects the dimerizing tail of the motor to the AAA+ ring.

270 In turn, the AAA+ ATPase torsinA is thought to regulate force transmi

271 anchors katanin to the microtubule while the AAA motor exerts the forces that extract tubulin dimers

272 bacterium tuberculosis collaborates with the AAA+ (ATPases associated with a variety of cellular acti

273 CT scans acquired from patients during their AAA surveillance pathway.

274 These AAA unfoldases include spastin, which plays a critical r

275 tion within the aorta, their contribution to AAA via distant alterations, particularly in the control

276 trengthened arterial framework refractory to AAA.

277 No relation to AAA risk was found for TLR4 SNPs.

278 1 (LAP1), an activator of ER-resident Torsin AAA+-ATPases, causes a failure in membrane removal from

279 nd establish TFEB as a novel target to treat AAA.

280 Relative survival of electively treated AAA patients was stable and persistently compromised [4-

281 A total of 214 endovascularly treated AAA patients were included.

282 The two AAA groups were homogeneous for age, sex, and most risk

283 n addition to a role for the Cdc48-Npl4-Ufd1 AAA-ATPase complex, Doa1 and a mitochondrial pool of the

284 uld be evidenced between stable and unstable AAA groups.

285 highly prevalent in both stable and unstable AAA patients.

286 RI scores was greater in those with unstable AAA (51.6% versus 23.3%).

287 able AAA (n = 30) and patients with unstable AAA (n = 31) based on aortic diameter, growth rate, and

288 quent in the group of patients with unstable AAA.

289 Volumetric AAA changes and demographic data of the cases with clini

290 29-variant PRS was strongly associated with AAA (odds ratio(PRS), 1.26 [95% CI, 1.18-1.36]; P(PRS)=2

291 subgingival plaque) and was correlated with AAA diameters and volumes.

292 of PD >6 mm were positively correlated with AAA size and thrombus volume.

293 of follow-up, 1125 women were diagnosed with AAA, 134 had premature menopause (11.9%), 93 underwent s

294 -7C/A SNPs were less common in patients with AAA than in healthy subjects (p < 0.0001 and p = 0.0004,

295 2029C/T SNP was more common in patients with AAA than in healthy subjects (p < 0.0001) and was associ

296 ry (NCT01599533), included 126 patients with AAA.

297 e identified a subset of the population with AAA prevalence greater than that observed in screening t

298 =0.2), likely has a causal relationship with AAA development.

299 sting ~18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of Eur

300 Despite worse outcomes for women with AAA, no studies have prospectively examined sex-specific

301 A total of 104 patients with AAAs and 112 healthy, unrelated volunteers were screened