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  1. 20821
    “…The processing of the amyloid precursor protein (APP) is one of the key events contributing to Alzheimer’s disease (AD) etiology. Canonical cleavages by β- and γ-secretases lead to Aβ production which accumulate in amyloid plaques. …”
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    The η-secretase-derived APP fragment ηCTF is localized in Golgi, endosomes and extracellular vesicles and contributes to Aβ production
  2. 20822
    “…In addition, we found that the GDNF-GFRA1 axis protects tumor cells from apoptosis under metabolic stress via regulating lysosomal functions and autophagy flux, and participates in the regulation of cytosolic calcium ion signalling in a RET-independent and non-canonical way. CONCLUSION: From our data we conclude that TAMs, homing around metastatic nests, induce the autophagy flux of GC cells and promote the development of liver metastasis via GDNF-GFRA1 signalling. …”
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    Tumor-associated macrophage-derived GDNF promotes gastric cancer liver metastasis via a GFRA1-modulated autophagy flux
  3. 20823
    “…Here, in an effort to improve MMP specificity, we incorporated the metal-binding non-canonical amino acids (NCAAs), 3,4-dihydroxyphenylalanine (L-DOPA) and (8-hydroxyquinolin-3-yl)alanine (HqAla), into the MMP-inhibitory N-terminal domain of TIMP2 (N-TIMP2) at selected positions that interact with the catalytic Zn(2+) ion (S2, S69, A70, L100) or with a structural Ca(2+) ion (Y36). …”
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    Utilizing genetic code expansion to modify N-TIMP2 specificity towards MMP-2, MMP-9, and MMP-14
  4. 20824
    “…We also showed that Ca(2+) homeostasis was mediated by transient receptor potential canonical‐1 (TRPC1) channels and inhibition of TRPC1, resulting in the loss of salivary acinar cells, which promoted alarmin release essential for immune cell infiltration/release of pro‐inflammatory cytokines. …”
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    Targeting alarmin release reverses Sjogren's syndrome phenotype by revitalizing Ca(2+) signalling
  5. 20825
    “…Interestingly, targeting molecular pathways canonically associated with analgesia did not replicate the effects of AS1. …”
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    A novel small molecule, AS1, reverses the negative hedonic valence of noxious stimuli
  6. 20826
    “…In both taste and HASM cells, TAS2Rs activate a canonical G(βγ)-mediated stimulation of Ca(2+) release from intracellular stores by activation of PLCβ (phospholipase Cβ). …”
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    A Par3/LIM Kinase/Cofilin Pathway Mediates Human Airway Smooth Muscle Relaxation by TAS2R14
  7. 20827
    “…Sleep loss is a defined feature seen early in many neurodegenerative disorders and contributes to memory impairments in Alzheimer’s disease. Canonical pathological hallmarks, β-amyloid, and tau, directly disrupt sleep, and neurodegeneration of locus coeruleus, hippocampal and hypothalamic neurons from tau proteinopathy causes disruption of the neuronal circuitry of sleep. …”
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    Proteostasis failure exacerbates neuronal circuit dysfunction and sleep impairments in Alzheimer’s disease
  8. 20828
    “…Accordingly, a correlation map between canonical cell-type proteins, such as epidermal growth factor and secreted phosphoprotein 1, and AI-based image features was obtained, which supports previous pathobiological results. …”
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    Discovery of Novel Digital Biomarkers for Type 2 Diabetic Nephropathy Classification via Integration of Urinary Proteomics and Pathology
  9. 20829
    “…Wilcoxon Rank Sum tests were performed to compare features of each microstate across the two groups [i.e., left hemisphere (LH) and right hemisphere (RH) stroke survivors]. The canonical microstate map D, characterized by a mostly frontal topography, displayed greater GEV, occurrence per second, and percentage of coverage in LH than in RH stroke survivors (p < 0.05). …”
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    EEG Microstates as a Signature of Hemispheric Lateralization in Stroke
  10. 20830
    “…METHODS: The levels of EZH2 and H3K27me3 were evaluated in 105 OC patients by immunohistochemistry (IHC) staining, and these patients were stratified based on these levels. Canonical and noncanonical binding sites of EZH2 were defined by chromatin immunoprecipitation sequencing (ChIP-Seq). …”
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    EZH2 mediated metabolic rewiring promotes tumor growth independently of histone methyltransferase activity in ovarian cancer
  11. 20831
    “…The binding modes of ADP at the canonical allosteric site and at the catalytic active site are clearly determined. …”
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    Structural basis of human PRPS2 filaments
  12. 20832
    “…Pathogenicity was predicted with in silico tools and the impact of 13 HIF-2β variants has been studied by using canonical and real-time reporter luciferase assays. …”
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    Comprehensive in silico and functional studies for classification of EPAS1/HIF2A genetic variants identified in patients with erythrocytosis
  13. 20833
    “…An additional HS-SPME-GC-MS-based analysis of the volatile compounds present in fermented grains samples led to the identification of 66 such compounds, with the highest levels of volatile acids, esters, and alcohols being detected in fermented grains from lower layer samples. A canonical correspondence analysis (CCA) suggested they were significant correlations between pit mud yeast communities and associated volatile compounds in fermented grains. …”
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    Yeast diversity in pit mud and related volatile compounds in fermented grains of chinese strong-flavour liquor
  14. 20834
    “…To further elucidate the physiological roles of this STAT3 non-canonical nuclear activity, we used a CRISPR/Cas9 zebrafish stat3 knock-out line. …”
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    STAT3 and HIF1α cooperatively mediate the transcriptional and physiological responses to hypoxia
  15. 20835
    “…Monocyte stimulation by NDPKs also resulted in activation of NF-κB and IRF pathways but did not include the formation of pyroptosomes or result in pyroptotic cell death which are pivotal features of canonical NLRP3 inflammasome activation. In the context of the growing importance of the NLRP3 inflammasome and IL-1β in AML and MDS, our findings now implicate pathogen NDPKs in the pathogenesis of these diseases.…”
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    Pathogen and human NDPK-proteins promote AML cell survival via monocyte NLRP3-inflammasome activation
  16. 20836
    “…One promising method to accomplish this is coupling bioorthogonal non-canonical amino acid tagging (BONCAT) with fluorescence activated cell sorting (FACS) which sorts cells based on whether or not they are producing new proteins. …”
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    BONCAT-FACS-Seq reveals the active fraction of a biocrust community undergoing a wet-up event
  17. 20837
    “…Surprisingly, we find that class 3 phosphatidylinositol-3-kinase (PI3K), known best for its essential role as a lipid kinase in endocytosis and lysosomal degradation by autophagy, has an overlooked nuclear function in gene transcription as a coactivator of the heterodimeric transcription factor and circadian driver Bmal1–Clock. Canonical pro-catabolic functions of class 3 PI3K in trafficking rely on the indispensable complex between the lipid kinase Vps34 and regulatory subunit Vps15. …”
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    Class 3 PI3K coactivates the circadian clock to promote rhythmic de novo purine synthesis
  18. 20838
    “…Unlike canonical CRISPR-Cas systems that rely on RNA-guided nucleases for target cleavage, CRISPR-associated transposases (CASTs) repurpose nuclease-deficient CRISPR effectors to facilitate RNA-guided transposition of large genetic payloads. …”
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    Mechanism of target site selection by type V-K CRISPR-associated transposases
  19. 20839
    “…CONCLUSION: The combination of BC-LI-0186 and trametinib inhibited the non-canonical mTORC1-activating function of LARS1. Our study demonstrated a new therapeutic approach for NSCLC without targetable driver mutations.…”
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    Combination of the LARS1 Inhibitor, BC-LI-0186 with a MEK1/2 Inhibitor Enhances the Anti-Tumor Effect in Non–Small Cell Lung Cancer
  20. 20840
    “…A cohort of patients receiving empiric treatment at the investigators’ discretion balanced for tumor entity and canonical prognostic factors served as control. RESULTS: A total of n = 22 progressive glioblastoma patients were eligible for this analysis. …”
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    Feasibility and tolerability of trofosfamide and etoposide in progressive glioblastoma
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