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br Results br Discussion Both ATM and ATR are key
2024-09-27
Results Discussion Both ATM and ATR are key regulators of the cellular response to DSBs, yet how exactly they function in concert is not well understood. Recent studies revealed that ATM is required for the resection of DSBs (Jazayeri et al., 2006, Myers and Cortez, 2006), a process necessary
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Mitochondria are key organelles involved in
2024-09-27
Mitochondria are key organelles involved in the mechanism of apoptosis (Xiong et al., 2014), and loss of ΔΨm is an important marker associated with mitochondrial dysfunction and cell death. We found that Mino induced ΔΨm impairment and nuclear fragmentation in Jurkat nuciferine in a concentration-d
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br Experimental procedures br Results br
2024-09-26
Experimental procedures Results Discussion Our biophysical and cellular analyses of mutant Aβ1–42 peptides support a role of the N-terminus of Aβ in peptide aggregation and toxicity. We demonstrate that double mutations constructed to humanize the rodent Aβ1–42 sequence result in a signific
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br Acknowledgments br Introduction Amyloid deposit
2024-09-26
Acknowledgments Introduction Amyloid deposit formation is defined by the aggregation of β-sheeted forms of proteins that appear as starch-like amorphous material [1], [2]. Using a Kongo red stain, amyloids show birefringence behavior and an apple-green to reddish multicolor emission. Extracere
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In our sequential model for
2024-09-26
In our sequential model for tau and Aβ deposition, we included the tau deposition in the medial temporal MRS 1220 in the absence of Aβ deposition, which is a pathological definition of primary age-related tauopathy (PART). Although the tau pathologies in PART and AD are almost identical in their ne
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Pathogen infected macrophages release exosomes associating w
2024-09-26
Pathogen-infected Heparin sodium release exosomes associating with pathogen-associated molecular patterns (PAMPs) such as LPS and lipoprotein derived from microorganisms [29,30]. Exosomes released by bacterially infected, but not uninfected, macrophages stimulate macrophages to release inflammatory
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Based on their different sources the
2024-09-26
Based on their different sources, the APN inhibitors (APNIs) can be divided into the natural products and synthetic compounds. Bestatin (1, Fig. 1), isolated from the Streptomyces oliuoreticuli by Umezawa et al., is the first reported and only marketed natural dipeptidomimetic inhibitor of APN. Afte
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br Methods The study population included neuropathologically
2024-09-26
Methods The study population included 64 neuropathologically confirmed AD patients (6 male, 58 female) that were recruited into a longitudinal follow-up study of patients with dementia of Alzheimer’s type from the geriatric department of Harjula Hospital in Kuopio, Finland. At baseline the patien
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br Discussion Missense mutations transversions of the first
2024-09-26
Discussion Missense mutations (transversions) of the first nucleotide of the phenylalanine tie2 at position 1174 (F1174) of the anaplastic lymphoma kinase gene can result in substitutions to leucine or valine (F1174L/V) while missense mutation (transversion) of the second nucleotide of the pheny
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The lactam emerged as lead candidate
2024-09-26
The lactam (6) emerged as lead candidate due to its high selectivity, outstanding potency (against ALK or in clinically known ALK mutants), low in vitro clearance, and low efflux potential. The lactam (6) was selected for further profiling against the resistant ALK mutants. Preclinical rat pharmacok
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In large biopsies series from ALK
2024-09-26
In large biopsies series from ALK+ NSCLC treated patients, the number of detected mutations increased after second generation ALKi (Gainor et al., 2016) and in one study were present in 56% of the entire cohort (Shaw et al., 2013b). For example, the rate of G1202R mutations increases from 2% in pos
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JP 1302 dihydrochloride br AHR mediates TCDD toxicity and wa
2024-09-26
AHR mediates TCDD toxicity and wasting syndrome TCDD causes numerous toxicities in laboratory animals, including teratogenesis, hepatic steatosis, thymic atrophy, immune dysfunction and a lethal wasting syndrome [17]. The dose-dependent sensitivity to TCDD-induced toxicities varies widely among l
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To further clarify the vascular cell types
2024-09-26
To further clarify the vascular cell types expressing AR subtypes, double immunofluorescence staining for ARs and vascular endothelial 58 4 or vascular smooth muscles was performed. As shown in Fig. 3, Fig. 4, overlay images show the expression of all ARs subtypes that we examined in vascular endot
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Our studies also reveal the normal
2024-09-26
Our studies also reveal the normal functional roles of the MIR. Interaction between the MIR loop and the N-terminal α helix nucleates conformational maturation of AChR subunits, thereby promoting assembly of mature AChRs [52], [55]. This interaction in homologous parts of all AChR subunits appears t
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Qualitative inspection of the single channel traces
2024-09-26
Qualitative inspection of the single-channel traces presented in both Figures 3 and 4 shows that within bursts of activity, βAnc-containing AChRs display a marked reduction in open probability. To quantify these differences in single-channel behavior, we performed dwell-time analysis under high-reso
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