ELIZA

return kwic search for significant out of >500 occurrences
583352 occurrences (No.14 in the rank) during 5 years in the PubMed. [cache]

394) To probe for the involvement of aging, we generated rejuvenated iPSC-derived neurons that showed no significant disease-related transcriptome signatures, a feature that is consistent with epigenetic clock and brain ontogenesis mapping, which indicate that fibroblast-derived iNs more closely reflect old adult brain stages.

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PMID:33910058 DOI:10.1016/j.stem.2021.04.004

2021 Cell stem cell

* Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer's patients.

- Sporadic Alzheimer's disease (AD) exclusively affects elderly people. Using direct conversion of AD patient fibroblasts into induced neurons (iNs), we generated an age-equivalent neuronal model. AD patient-derived iNs exhibit strong neuronal transcriptome signatures characterized by downregulation of mature neuronal properties and upregulation of immature and progenitor-like signaling pathways. Mapping iNs to longitudinal neuronal differentiation trajectory data demonstrated that AD iNs reflect a hypo-mature neuronal identity characterized by markers of stress, cell cycle, and de-differentiation. Epigenetic landscape profiling revealed an underlying aberrant neuronal state that shares similarities with malignant transformation and age-dependent epigenetic erosion. To probe for the involvement of aging, we generated rejuvenated iPSC-derived neurons that showed no significant disease-related transcriptome signatures, a feature that is consistent with epigenetic clock and brain ontogenesis mapping, which indicate that fibroblast-derived iNs more closely reflect old adult brain stages. Our findings identify AD-related neuronal changes as age-dependent cellular programs that impair neuronal identity.

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(1)20 increase	(21)5 and	(41)2 DDIs	(61)2 heterogeneity
(2)16 differences	(22)5 improvement	(42)2 adverse	(62)2 impacts
(3)15 difference	(23)5 results	(43)2 antioxidant	(63)2 impairment
(4)13 reduction	(24)5 risk	(44)2 at	(64)2 implications
(5)11 changes	(25)4 amount	(45)2 barriers	(65)2 increased
(6)10 association	(26)4 associations	(46)2 being	(66)2 induction
(7)10 improvements	(27)4 burden	(47)2 benefits	(67)2 interaction
(8)10 positive	(28)4 clinical	(48)2 cause	(68)2 loci
(9)10 role	(29)4 public	(49)2 challenges	(69)2 morbidity
(10)9 impact	(30)3 advances	(50)2 clusters	(70)2 number
(11)8 decrease	(31)3 as	(51)2 cognitive	(71)2 personal
(12)8 in	(32)3 evidence	(52)2 consequence	(72)2 portion
(13)7 null	(33)3 expression	(53)2 contribution	(73)2 relationship
(14)7 effect	(34)3 gaps	(54)2 correlation	(74)2 sequence
(15)6 effects	(35)3 health	(55)2 factor	(75)2 survival
(16)6 increases	(36)3 highly	(56)2 finding	(76)2 than
(17)6 progress	(37)3 inhibition	(57)2 findings	(77)2 therapeutic
(18)6 proportion	(38)3 interactions	(58)2 for	(78)2 trend
(19)6 reductions	(39)3 predictors	(59)2 fraction	(79)2 variation
(20)5 (p	(40)3 upregulation	(60)2 functional	(80)2 variations

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--- WordNet output for significant --- =>意義深い, 重大な, 意味のある, 意味ありげな, 重要な Overview of adj significant The adj significant has 4 senses (first 4 from tagged texts) 1. (18) significant, important -- (important in effect or meaning; "a significant change in tax laws"; "a significant change in the Constitution"; "a significant contribution"; "significant details"; "statistically significant") 2. (9) significant, substantial -- (fairly large; "won by a substantial margin") 3. (3) significant -- (too closely correlated to be attributed to chance and therefore indicating a systematic relation; "the interaction effect is significant at the .01 level"; "no significant difference was found") 4. (2) meaning, pregnant, significant -- (rich in significance or implication; "a meaning look") --- WordNet end ---