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How does the ATM to ATR switch
2025-01-23

How does the ATM-to-ATR switch occur at DSBs? The progressive attenuation of ATM activation could be attributed to the loss of DNA structures that activate ATM, or to the generation of DNA structures that interfere with ATM activation. Our finding that SSOs do not directly affect the binding of pur
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Infections inflammation and corneal transplant can all cause
2025-01-23

Infections, inflammation, and corneal transplant can all cause corneal neovascularization via upregulation of inflammatory cytokines, which attract myeloid lipoxygenase inhibitor into the cornea. These myeloid cells establish a cycle of cytokine secretion and further myeloid cell recruitment in the
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A straightforward synthetic pathway was adopted
2025-01-23

A straightforward synthetic pathway was adopted to synthesize the target compounds as outlined in . The starting chloromethylquinazolinones (–) were synthesized from anthranilic SB 258719 hydrochloride in two steps following reported procedures., , , The first step involves chloroacetylation of an
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The inflammatory cytokine IL is an additional
2025-01-22

The inflammatory cytokine IL-6 is an additional factor that has been hypothesized to contribute to epinephrine-mediated repression of drug detoxifying proteins such as CYP3A4 (Aninat et al., 2008). Indeed, this CYP is well-known to be repressed by IL-6 (Dickmann et al., 2011) and epinephrine has pre
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Given the powerful and ubiquitous nature of
2025-01-22

Given the powerful and ubiquitous nature of adenosine action within the CNS, basal levels of extracellular adenosine are carefully regulated and are estimated to be in the region of 30–300 nM (Fredholm et al., 2001). The two main pathways for the control of extracellular adenosine involve phosphoryl
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The ARHL locus ahl that contributes to the
2025-01-22

The ARHL locus (ahl) that contributes to the hearing loss in the C57BL/6J mouse has been mapped to chromosome 10 (Erway et al., 1993, Johnson et al., 1997). It has been shown that strains susceptible to early onset ARHL carry a specific mutation in the cadherin 23 gene (Cdh23), which encodes a compo
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Thirty six of the analogs synthesized showed ATX inhibition
2025-01-22

Thirty-six of the analogs synthesized showed ATX inhibition greater than 50% at 10μM with FS-3, twelve of which had improved potency over the lead (Fig. 5). Of these, 22 was sub-micromolar (IC50 670nM). The 3,5-dichlorophenoxy ring of 22 is reminiscent of the 3,5-dichlorophenylthiourea ring in Hoegl
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pla2 inhibitor Among the AXL positive tumors that we screene
2025-01-22

Among the AXL-positive tumors that we screened, the TNBC cell line MDA-MB-231 showed the highest AXL expression level. Additionally, AXL protein levels were higher in TNBC patient samples than in other breast cancers. Considering the difficulty of, and the urgent need for, effective treatments of TN
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GABAB receptor is associated with brain
2025-01-22

GABAB receptor is associated with WDR5 0103 and behavioral diseases, including epilepsy, spasticity, anxiety and neuropathic pain (Bettler et al., 2004, Bowery et al., 2002, Froestl, 2010). Baclofen, a clinical drug and selective GABAB receptor agonist, is used to treat muscle spasticity in patient
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Baricitinib receptor In a recent issue of Minokoshi and coll
2025-01-21

In a recent issue of , Minokoshi and colleagues have added more light to our understanding of the role of hypothalamic AMPK in the regulation of energy balance. Previous seminal work from the same group suggested that AMPK in the PVH might be involved in the modulation of feeding . Here, they show
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Our present result that week
2025-01-21

Our present result that ≤2-week-old 150ΔPKA mice express normal LTP that does not depend on CP-AMPARs also supports the collective findings of previous work showing that LTP mechanisms are remarkably adaptable in juvenile animals compared with adults. In particular, GluA1 knockout, S845A/S831A, and
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br Conclusion br Acknowledgement This study was supported by
2025-01-21

Conclusion Acknowledgement This study was supported by NIH/NINDSR01 NS036812-16. Introduction Lipoxygenases (LOXs) are a heterogeneous family of enzymes that catalyze the peroxidation of polyunsaturated fatty acids (PUFAs). By oxidizing free PUFAs, they were shown to contribute to the gene
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br Impact of global AHR deficiency on diet induced obesity
2025-01-21

Impact of global AHR deficiency on diet-induced obesity Two subsequent studies in which AHR function was affected at the whole animal level corroborated the role of AHR in dietary obesity. Xu et al. [14] showed that on a high-fat diet, both AHR-deficient Ahr−/− and hemizygous Ahr+/− mice gained
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Mass spectrometry MS analysis and selective enrichment metho
2025-01-21

Mass spectrometry (MS) analysis and selective enrichment methods of phosphorylated proteins are powerful tools that can help address these challenges. Recent advances in MS have made it possible to analyze signaling pathways by facilitating high-throughput identification of phosphorylation sites wit
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Cell viability assay A clear link between ADR stimulation an
2025-01-21

A clear link between α2-ADR stimulation and decreased respiration in β-cells is established and consistent with proteomics data. Current discoveries in islets have identified physical interactions between ADR-coupled G proteins and cellular components such as insulin vesicles and ion channels (Zhao
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