ライフサイエンスコーパス: ALR

1 ALR concentrations were then determined in intact livers

2 ALR depletion from ALR (flox/flox)/Alb-Cre [ALR-L-knocko

3 ALR depletion from hepatocytes in vivo downregulated per

4 ALR depletion from primary hepatocytes increased oxidati

5 ALR forms large amounts of neutral semiquinone during ae

6 ALR has trophic effects on regenerating liver.

7 ALR in the various liver cells was localized with immuno

8 ALR is a cellular process controlled by mTOR which regen

9 ALR is a convenient and useful regression technique for

10 ALR islets were found to be remarkably resistant to two

11 ALR mice are unusual in their high constitutive expressi

12 ALR resistance to diabetogenic immune systems was determ

13 ALR was delivered from day 1 through day 14, in doses of

14 ALR was measured in serum of human nonalcoholic steatohe

15 ALR-L-KO mice (1-, 2-, and 4 wk old) and Adeno-Cre-trans

16 ALR-L-KO mice provide a useful model for investigating t

17 on of ALRs, we generated mice lacking all 13 ALR genes.

18 e column (BCR) and an internal loop airlift (ALR) bioreactors of 2.3 L for the abatement of N2O from

19 t of impaired lysosomal tubulation alongside ALR activation is massive cell death.

20 ed mice with liver-specific deletion of ALR (ALR-L-KO) using the albumin-Cre/LoxP system.

21 itive genetic variance but also that AFR and ALR are positively genetically correlated.

22 In addition, hepatic ALR and ALR mRNA were assayed with Western blotting and reverse-

23 l water properties differing between CTD and ALR observations reveal correlations to carbonate parame

24 and the reciprocal with NOD nuclear DNA and ALR mtDNA (NOD.mt(ALR)).

25 gene, 9GL, with similarity to yeast ERV1 and ALR genes.

26 ET, but not WT, mice developed fibrosis; and ALR-H-KO mice progressed to cirrhosis.

27 tocyte-specific ALR-knockout (ALR-H-KO), and ALR-heterozygous (ALR-H-HET) mice.

28 ALS/Lt and ALR/Lt are inbred mouse strains selected for susceptibil

29 issues were collected from ALR-L-KO mice and ALR(floxed/floxed) mice (controls) and analyzed by histo

30 neage leukemia 4 (MLL4; also called MLL2 and ALR) enzymatically generates trimethylated histone H3 Ly

31 he close MHC relatedness between the NOD and ALR strains (H2-Kd and H2-Ag7 identical) allowed us to e

32 rary to previous belief, the ALR peptide and ALR mRNA were present in comparable concentrations in th

33 rucial for endosome-lysosome trafficking and ALR, accumulated in GCase deficient cells, supporting th

34 NLRs and ALRs engage caspase-1, in most cases requiring the adapt

35 Unlike MLL1, MLL2 (also known as ALR/MLL4) and its homolog MLL3 are not well-understood.

36 Because ALR-1 and similar proteins (Drosophila Aristaless and hu

37 tion adversely affects the stability of both ALR forms: e.g., by decreasing the melting temperature b

38 We found that both ALRs bind NETs in vitro and in SLE renal tissues.

39 nerated in NOD and C3H/HeJ islets but not by ALR islets.

40 lceramide homeostasis which could compromise ALR.

41 In contrast, ALR/Lt islets remained viable and retained glucose-stimu

42 ALR depletion from ALR (flox/flox)/Alb-Cre [ALR-L-knockout (KO)] mouse causes robust steatosis and a

43 HF/HC feeding decreased ALR expression in all groups of mice.

44 Defective ALR in Inpp5k-/- myoblasts was characterized by enlarged

45 hallenged metabolically with the HF/HC diet; ALR-H-KO mice gained the least weight and had the least

46 3 is not sufficient for TRN differentiation; ALR-1 provides a second positive feedback loop that incr

47 e R194H mutation on the stability of dimeric ALR and complement the in vivo observations of Di Fonzo

48 ulfide, a helix-rich domain, and then an Erv/ALR domain.

49 ace, and a larger protein containing the ERV/ALR domain, quiescin-sulfhydryl oxidase (QSOX).

50 domain and the proximal disulfide of the Erv/ALR domain.

51 The FAD prosthetic group of the ERV/ALR family of sulfhydryl oxidases is housed at the mouth

52 redox properties between members of the ERV/ALR family of sulfhydryl oxidases provides insights into

53 ulfhydryl oxidases and is related to the ERV/ALR family of sulfhydryl oxidases.

54 irus in which the E10R gene encoding an ERV1/ALR family protein was repressed, the disulfide bonds of

55 ial disulfide relay system of Mia40 and Erv1/ALR facilitates import of the small translocase of the i

56 Multiple alignments of ERV1/ALR proteins indicated an invariant C-X-X-C motif, but n

57 sulfhydryl:cytochrome c oxidoreductase Erv1/ALR are essential for oxidative protein import into the

58 Proteins of the ERV1/ALR family are encoded by all eukaryotes and cytoplasmic

59 By extension, the ERV1/ALR family may represent a ubiquitous class of cellular

60 pstream component, E10R, belongs to the ERV1/ALR family of FAD-containing sulfhydryl oxidases that us

61 vaccinia virus protein belonging to the ERV1/ALR family, has a redox function and is required for vir

62 , with similar properties to the established ALR autoantigen interferon-inducible protein 16 (IFI16).

63 cells from all Kd-expressing strains except ALR.

64 suggesting a mechanism whereby extracellular ALR-NET interactions may promote sustained IFN signaling

65 Our work suggests that extracellular ALRs bind NETs, leading to DNase resistant nucleoprotein

66 y express the auxiliary transcription factor ALR-1 (Aristaless related), which ensures, but does not

67 n the gene encoding the transcription factor ALR-1 in Caenorhabditis elegans result in variable touch

68 e binding sites of 22 transcription factors (ALR-1, BLMP-1, CEH-14, CEH-30, EGL-27, EGL-5, ELT-3, EOR

69 White adipose tissue of HF/HC-fed ALR-deficient mice developed strong inflammation, indica

70 HF/HC-fed ALR-H-HET mice were more resistant to glucose challenge

71 HF/HC-fed ALR-H-HET, but not WT, mice developed fibrosis; and ALR-

72 The flavoprotein ALR receives two electrons per subunit from Mia40, which

73 bout a 100-fold better electron acceptor for ALR than oxygen when DTT is the reducing substrate.

74 SLE renal tissues were examined for ALR-containing NETs by confocal microscopy.

75 ated cells, suggesting an important role for ALR in hESC homeostasis.

76 results indicate a cell autonomous role for ALR-1 in maintaining cell shape.

77 Furthermore, we demonstrate a role for ALR-1 in the proper morphogenesis of the anterior hypode

78 n a significantly greater proportion of FP + ALR-treated recipients than those animals treated with v

79 Liver tissues were collected from ALR-L-KO mice and ALR(floxed/floxed) mice (controls) and

80 ALR depletion from ALR (flox/flox)/Alb-Cre [ALR-L-knockout (KO)] mouse caus

81 vivo, ALS/Lt islets were distinguished from ALR/Lt islets by more extensive necrotic changes.

82 d the mechanism whereby isolated islets from ALR mice resisted proinflammatory stress mediated by com

83 of hydrogen peroxide and NO than islets from ALR mice.

84 Podocyte outgrowth from ALR (-/-) glomeruli was still increased, however, confir

85 A dominant genetic trait from ALR/Lt controlling this unusual AL resistance was indica

86 We have cloned a novel human gene, ALR, which encodes a gigantic 5262 amino acid long prote

87 Hence, ALR/Lt islets resist cytokine-induced diabetogenic stres

88 Hepatic ALR deficiency may be a critical predisposing factor for

89 In addition, hepatic ALR and ALR mRNA were assayed with Western blotting and

90 further unexpected finding was that hepatic ALR levels decreased for 12 hours after 70% hepatectomy

91 R-knockout (ALR-H-KO), and ALR-heterozygous (ALR-H-HET) mice.

92 However, ALR.mt(NOD) mitochondria supported by either complex I o

93 et al. described an R194H mutation of human ALR that led to cataract, progressive muscle hypotonia,

94 est that, contrary to a recent report, human ALR is a disulfide-bridged dimer (linked via C15-C124) w

95 ation, and functions of the murine and human ALRs and identify novel activators of STING-dependent IF

96 We illustrate ALR with an application to caries aggregation using a da

97 Nuclear and mitochondrial genomes combine in ALR/Lt mice to produce systemically elevated defenses ag

98 vels of steatosis and apoptosis decreased in ALR-L-KO mice, and numbers of ALR-expressing cells incre

99 ied as the rare H2-Ddx recently described in ALR/Lt, another NOD-related strain.

100 on of autolysosomes, reflecting a failure in ALR.

101 ted antioxidant defenses previously found in ALR/Lt pancreas were extended to isolated islets, which

102 ing, and IL17-producing cells was greater in ALR-H-KO than ALR-H-HET and lowest in WT mice.

103 number in ALR-H-KO mice, and the increase in ALR-H-HET was greater than that in WT mice except for IL

104 (+) regulatory T-cell frequency was lower in ALR-H-HET than WT mice and further reduced in ALR-H-KO m

105 lin resistance, the magnitude being lower in ALR-H-KO mice.

106 ase in NOD-Rag and C3H/HeJ islets but not in ALR islets.

107 /HC feeding did not increase their number in ALR-H-KO mice, and the increase in ALR-H-HET was greater

108 e model for the electron-transfer pathway in ALR.

109 in localize the heightened ROS production in ALR.mt(NOD) to complex III and identified complex I as t

110 LR-H-HET than WT mice and further reduced in ALR-H-KO mice; HF/HC reduced regulatory T-cell frequency

111 We have recently shown that resistance in ALR/Lt correlated with constitutively elevated systemic

112 rom all mt-Nd2(c)-encoding strains including ALR.mt(NOD), non-obese diabetic (NOD), and C57BL/6 (B6).

113 ne and recombinant ALR (rALR) both inhibited ALR depletion-induced miR-540 expression and lipid accum

114 Investigating ALR-1 functions in C. elegans may yield insights into th

115 clone or by chimerizing lethally irradiated ALR or reciprocal (ALR x NOD)F1 recipients with NOD bone

116 in and noticed that a subset of MLL2 (KMT2D, ALR, MLL4)-associated Kabuki syndrome missense mutations

117 type (WT), hepatocyte-specific ALR-knockout (ALR-H-KO), and ALR-heterozygous (ALR-H-HET) mice.

118 some individuals have earlier AFR and later ALR than expected.

119 itment of the inflammasome adaptor ASC links ALRs to the activation of caspase-1.

120 d physiological substrates of short and long ALR forms.

121 perform a phylogenetic analysis of mammalian ALRs, revealing a remarkable diversification of these re

122 us provides a mechanistic link between MIA40/ALR import machinery and cytosolic Fe/S cluster maturati

123 Mechanistically, MIA40/ALR facilitates the mitochondrial import of ATP-binding

124 s of ALR, a principal component of the MIA40/ALR protein import pathway, results in impaired cytosoli

125 Anti-miR-540 mitigated ALR depletion-induced steatosis and prevented loss of PP

126 one lysine methyltransferases (HKMTs), MLL2 (ALR), forming a complex that methylates lysine 4 of hist

127 of mammalian Mixed Lineage Leukemia 2 (MLL2/ALR), a core component of COMPASS-like nuclear receptor

128 Moreover, ALR dysfunction was accompanied by impairment of macroau

129 ntribute to each of these pathways, but most ALRs remain uncharacterized.

130 ed from either the NOD (NIT-1) or the NOD.mt(ALR) (NIT-4) were also created to compare their suscepti

131 compared with both parental strains, NOD.mt(ALR) or C57BL/6 controls.

132 nt (ALR)/Lt-derived mt-Nd2(a) allele (NOD.mt(ALR)) were created and compared with standard NOD (carry

133 l with NOD nuclear DNA and ALR mtDNA (NOD.mt(ALR)).

134 ted: one with ALR nuclear DNA and NOD mtDNA (ALR.mt(NOD)) and the reciprocal with NOD nuclear DNA and

135 Here, we identify five novel murine ALRs and perform a phylogenetic analysis of mammalian AL

136 Therefore, in muscle, ALR is indispensable for lysosome homeostasis during aut

137 Here, we identified a non-NLR/ALR human protein that stimulates inflammasome assembly:

138 interfere with the interaction between NLRPs/ALRs and ASC to prevent nucleation of ASC and therefore

139 The otherwise normal ALR-H-HET mice gained more weight and steatosis than WT

140 inhibitor of DNA virus-induced activation of ALR inflammasomes in vivo.

141 the dithiothreitol (DTT) oxidase activity of ALR.

142 a40 and requires tightly balanced amounts of ALR.

143 The analysis of ALR expression showed that its approximately 18 kb long

144 veloped mice with liver-specific deletion of ALR (ALR-L-KO) using the albumin-Cre/LoxP system.

145 created mice with liver-specific deletion of ALR to study its function.

146 veloped mice with liver-specific deletion of ALR, and showed that it is required for mitochondrial fu

147 Downregulation of ALR impairs mitochondrial ABCB8 import, reduces cytoplas

148 In addition to the cytokine form of ALR (sfALR) that circulates in serum, a longer form, lfA

149 er of both the short, cytokine-like, form of ALR (sfALR), and a longer form (lfALR) which resides in

150 free radical stress extended to the level of ALR/Lt pancreatic islets.

151 ers of ALR-L-KO mice contained low levels of ALR and adenosine triphosphate (ATP); they had reduced m

152 Hepatic levels of ALR were also low in ob/ob mice and alcohol-fed mice wit

153 Levels of ALR were lower in liver tissues from patients with advan

154 Two weeks after birth, livers of ALR-L-KO mice contained low levels of ALR and adenosine

155 ase subunit ATP5G1 were reduced in livers of ALR-L-KO mice, indicating defects in mitochondrial fatty

156 me biogenesis did not compensate for loss of ALR in Inpp5k-/- muscle, revealing a dependence on this

157 Here, we demonstrate that loss of ALR, a principal component of the MIA40/ALR protein impo

158 We investigated mechanisms of ALR depletion-induced steatosis.

159 s decreased in ALR-L-KO mice, and numbers of ALR-expressing cells increased, along with ATP levels.

160 tosis regresses by 4 wk upon reappearance of ALR-expressing hepatocytes.

161 mphasize the importance of the regulation of ALR inflammasomes in monocytes and macrophages.

162 intaining homeostasis, but the regulation of ALR inflammasomes is poorly understood.

163 nerate neoantigens; therefore, resistance of ALR islets to nitrotyrosine formation may, in part, expl

164 In this work, we investigate the role of ALR-1, the Caenorhabditis elegans aristaless orthologue,

165 nown about the cellular/subcellular sites of ALR synthesis in the liver, or about the release and dis

166 ere assigned by comparing the NMR spectra of ALR bound to oxidized and reduced flavin adenine dinucle

167 Finally, treatment of ALR-L-KO mice with rALR between 1 and 2 wk prevented miR

168 To rigorously explore the function of ALRs, we generated mice lacking all 13 ALR genes.

169 and oligomerization, leucine-rich repeat) or ALR (absent in melanoma 2-like receptor) proteins to act

170 re resistant to glucose challenge than WT or ALR-H-KO mice.

171 the homodimeric FAD-dependent thiol oxidase ALR.

172 arities in structure and expression pattern, ALR is likely to play a similar role to ALL-1 and trx, a

173 ntrol neutrophils and combined with purified ALR proteins in immunofluorescence and DNase protection

174 III, the Escherichia coli alanine racemase (ALR), is a promiscuous cystathionine beta-lyase (CBL).

175 were integrated into the Autosub Long-Range (ALR) autonomous underwater vehicle (AUV) and deployed in

176 we raised antibodies in rabbits against rat ALR for development of an enzyme-linked immunosorbent as

177 Although the crystal structure of rat ALR shows a proximal disulfide (C62-C65) poised to inter

178 fferent air-to-liquid mass flow rate ratios (ALRs).

179 Certain members of the AIM2-like receptor (ALR) gene family contribute to each of these pathways, b

180 The AIM2-like receptor (ALR) locus was necessary for the inflammatory glomerulon

181 absent in melanoma 2 (AIM2)-like receptors (ALR).

182 The AIM-like receptors (ALRs) are IFN-inducible innate sensors that form supramo

183 osolic DNA is sensed by AIM2-like receptors (ALRs) during bacterial and viral infections and in autoi

184 aining a PYD (NLRPs) or AIM2-like receptors (ALRs), which interact with the PYD- and CARD-containing

185 this pathway, including AIM2-like receptors (ALRs).

186 izing lethally irradiated ALR or reciprocal (ALR x NOD)F1 recipients with NOD bone marrow.

187 Antioxidant N-acetylcysteine and recombinant ALR (rALR) both inhibited ALR depletion-induced miR-540

188 The accessory lateral rectus (ALR) EOM was present in all specimens, but was small, in

189 e show that autophagy lysosomal reformation (ALR) is compromised in cells lacking functional GCase.

190 K regulates autophagic lysosome reformation (ALR), a lysosome recycling pathway, in muscle.

191 pivotal for autophagic lysosome reformation (ALR), a pathway that generates new lysosomes.

192 s termed autophagosome-lysosome reformation (ALR).

193 ryl oxidase augmenter of liver regeneration (ALR) binds FAD in a helix-rich domain that presents a Cx

194 Augmenter of liver regeneration (ALR) is a hepatotrophic protein originally identified by

195 Augmenter of liver regeneration (ALR) is a newly described polypeptide growth factor foun

196 Augmenter of liver regeneration (ALR) is both a growth factor and a sulfhydryl oxidase th

197 The augmenter of liver regeneration (ALR) protein is critical for lipid homeostasis and mitoc

198 nic loss of Augmenter of Liver Regeneration (ALR) results in mitochondrial myopathy with cataracts; h

199 Levels of augmenter of liver regeneration (ALR), a multifunctional protein, are reduced in steatohe

200 ryl oxidase augmenter of liver regeneration (ALR), and the intracellular glutathione pool.

201 ryl oxidase augmenter of liver regeneration (ALR).

202 Augmenter of liver regeneration (ALR, encoded by GFER) is a widely distributed pleiotropi

203 Augmenter of liver regeneration (ALR; hepatopoietin) is a recently discovered enigmatic f

204 ic factors (augmenter of liver regeneration [ALR], insulin-like growth factor-II [IGF-II], and hepato

205 posable element (LINE), or satellite region (ALR/Alpha) DNA, and three additional clones were near Al

206 such data, alternating logistic regressions (ALR) is a computationally efficient alternative method,

207 oduction (AFR) and age at last reproduction (ALR) in a free-ranging mute swan (Cygnus olor) populatio

208 analysis of outcrosses between T1D-resistant ALR and T1D-susceptible NOD mice.

209 ble NOD mice with the strongly T1D-resistant ALR strain.

210 J mice conplastic for the alloxan resistant (ALR)/Lt-derived mt-Nd2(a) allele (NOD.mt(ALR)) were crea

211 th nuclear genes from the alloxan-resistant (ALR) strain, mt-Nd2(c) increases ROS from complex III.

212 Recombinant GCase treatment reversed ALR inhibition and lysosomal dysfunction.

213 nd stored; the cultured hepatocytes secreted ALR into the medium in a time-dependent fashion.

214 Serum ALR was also significantly lower in patients with NASH.

215 Hepatic and serum ALR levels were significantly reduced in patients with N

216 In the meantime, circulating (serum) ALR levels increased up to 12 hours and declined thereaf

217 AFLD) in wild-type (WT), hepatocyte-specific ALR-knockout (ALR-H-KO), and ALR-heterozygous (ALR-H-HET

218 contrast to islets from other mouse strains, ALR islets expressed constitutively higher glutathione r

219 1Mag and nine Swiss-derived, inbred strains: ALR/LtJ, ALS/LtJ, APN, APS, ICR/HaRos, NOD/LtJ, NON/LtJ,

220 In a yeast expression system, ALR-1 enhances MEC-3/UNC-86-dependent transcription from

221 In all in vivo systems, ALR and F1 female recipients of NOD marrow remained IDDM

222 producing cells was greater in ALR-H-KO than ALR-H-HET and lowest in WT mice.

223 We conclude that ALR deficiency-mediated oxidative stress induces generat

224 We demonstrate that ALR binding causes NETs to resist degradation by DNase I

225 tend our previously advanced hypothesis that ALR and other hepatotrophic factors play an important ro

226 Our data imply that ALR is critical for cell survival under nutrient stress

227 Our studies indicate that ALR-1 is required for maintenance of the amphid organ st

228 iption from the mec-3 promoter, showing that ALR-1 can enhance bulk mec-3 expression.

229 Genetic interaction tests also suggest that ALR-1 may function cooperatively with the cell adhesion

230 oblasts with GBA1 mutations, suggesting that ALR is compromised.

231 We found that ALRs are dispensable for the type I interferon (IFN) res

232 We also found that ALRs do not contribute to autoimmune disease in the Trex

233 Our findings indicate that ALRs are dispensable for the ISD response and suggest th

234 The ALR gene and gene product were subsequently described, b

235 The ALR gene was mapped to chromosome band 12q12-13, adjacen

236 The ALR is unlikely to contribute to horizontal strabismus i

237 ds to this element but does not assemble the ALR complex.

238 Contrary to previous belief, the ALR peptide and ALR mRNA were present in comparable conc

239 In conclusion, the ALR mouse presents a unique opportunity to identify domi

240 In conclusion, the ALR/Lt mouse may provide important insight into genetic

241 As expected, the ALR active site was enlarged by the Y274F substitution,

242 proximately 57% and approximately 84% in the ALR and BCR, respectively.

243 Using interpolation, the ALR-sensor data set is compared against CTD co-samples.

244 Here, we investigate the ALR absent in melanoma 2 (AIM2) as a novel autoantigen i

245 ALR, characterizing at the atomic level the ALR intermediates that allow electrons to rapidly flow t

246 PTIP promotes assembly of the ALR complex and H3K4 methylation at a PAX2-binding DNA e

247 Characteristics of the ALR did not correlate with strabismus.

248 hat Mnr2 could function independently of the ALR genes.

249 and total alkalinity (TA) while onboard the ALR.

250 till increased, however, confirming that the ALR locus is dispensable for AIM2 effects on epithelial

251 uncovered 16 positives, one of which was the ALR gene, whose similarity to three of gliadin's five do

252 Whether the ALRs are essential for activation of this pathway remain

253 tients positive for antibodies against these ALRs.

254 This ALR/Lt islet resistance extended to hydrogen peroxide, a

255 Thus, ALR appears to be constitutively expressed in hepatocyte

256 , which competes with ASC for recruitment to ALRs, as an inhibitor of DNA virus-induced activation of

257 2-, and 4 wk old) and Adeno-Cre-transfected ALR (flox/flox) hepatocytes were used for in vivo and in

258 This inability of cytokine-treated ALR islets to up-regulate inducible NO synthase and prod

259 observed in Aim2 (-/-) mice, as NTS-treated ALR (-/-) mice displayed equal levels of injury as wild-

260 These findings validate ALRs as key activators of the antiviral response and pro

261 rror-prone PCR and selection yielded variant ALR(Y274F), which catalyzes cystathionine beta-eliminati

262 ssed autophagy and lysosome repopulation via ALR inhibition.

263 d hyperglycemia and hypoinsulinemia, whereas ALR/Lt mice maintained normal plasma insulin and glucose

264 Ag7 identical) allowed us to examine whether ALR islet cells could survive autoimmune destruction by

265 cyte was the predominant liver cell in which ALR was synthesized and stored; the cultured hepatocytes

266 ve phosphorylation and in cell growth, while ALR has hepatotrophic activity.

267 tyrosine formation may, in part, explain why ALR mice are resistant to type 1 diabetes when reconstit

268 Consistent with ALR-1 expression within the amphid socket cell, our resu

269 PTIP copurifies with ALR, MLL3, and other components of a histone methyltrans

270 on tubules, which we propose interfered with ALR completion.

271 astic mouse strains were generated: one with ALR nuclear DNA and NOD mtDNA (ALR.mt(NOD)) and the reci

272 tion for the pathology seen in patients with ALR mutations.

273 Of the group treated with ALR at 40 ng/kg/day for 14 days, 89% (eight of nine) wer

274 Of the group treated with ALR at 400 ng/kg/day for 14 days, 88% (seven of eight) w

275 re the mechanism of the electron flux within ALR, characterizing at the atomic level the ALR intermed