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A high throughput screening campaign led
2023-09-27
A high-throughput screening campaign led to the discovery of the first series of both potent and selective ATR kinase inhibitors by Vertex Pharmaceuticals (Charrier et al., 2011). One of these compounds, VE-821, was shown to be a potent ATP-competitive inhibitor of ATR with minimal cross-reactivity
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anatoxin a Introduction Initially postulated to represent
2023-09-27
Introduction Initially postulated to represent the main source of ATP production in eukaryotic cells, mitochondria are recently recognized to perform manifold essential functions beyond energy production, impacting most areas of cell biology and medicine [1]. Mitochondrial metabolism is both the ba
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At the outset of targeting the two Gln
2023-09-27
At the outset of targeting the two Gln756 side-chain rotamers, it was unclear which rotational isomer would lead to more potent ASK1 inhibitors. While such a preference might have been anticipated, the cohort of ASK1 inhibitors in Table 3 did not provide any guidance regarding which of the Gln756 am
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br Conclusions A large body
2023-09-27
Conclusions A large body of evidence indicates that oxidative stress is involved in the pathogenesis of NDDs. Hence, reducing oxidative stress or suppressing its downstream pathways may be beneficial for the treatment of these diseases, especially such chronic diseases as AD or glaucoma. Here we
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The contractility index showed positive inotropic effects of
2023-09-27
The contractility index showed positive inotropic effects of apelin in both doses at min 5 (Fig. 3, Fig. 5). Although the mean arterial pressure did not recover to the baseline, the contractility index increased, the relaxation index (tau) and ±dp/dt max returned back to their baseline, and left ven
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Hyperactivity of the hypothalamus pituitary
2023-09-27
Hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis, which is well described in MDD (Pariante and Lightman, 2008, Marques et al., 2009), is also observed in AD and results in increased glucocorticoid (GC, cortisol in primates) levels in blood and CSF (Davis et al., 1986, Martignoni et al.
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br Materials and Methods br Author Contributions br Conflict
2023-09-27
Materials and Methods Author Contributions Conflicts of Interest Acknowledgments We thank Francine Jodelka for technical assistance and Gopal Thinakaran for the CTM-1 antibody. This work was financially supported by RFUMS internal research funding and NIHS10 OD 010662. Introduction A
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The first identified auxiliary subunit stargazin is essentia
2023-09-27
The first identified auxiliary subunit, stargazin, is essential for AMPAR function in cerebellar granule neurons (Hashimoto et al., 1999). Subsequently, a family of six transmembrane AMPAR regulatory proteins (TARPs) were defined that modify channel trafficking, gating, and pharmacology (Kato and Br
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br Polymorphic variation ERAP is polymorphic and several
2023-09-27
Polymorphic variation ERAP1 is polymorphic and several single nucleotide polymorphisms (SNPs) in its gene that encode amino CFDA SE Cell Tracer Kit changes have been associated with predisposition to a variety of diseases, ranging from viral infections to cancer and autoimmunity (Alvarez-Navarro
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Since HETEs and lipoxins the
2023-09-27
Since HETEs and lipoxins, the downstream products of 12/15-LOX from AA, may alter cellular proliferation and apoptosis,31, 32 and possibly explain the increase of tumour progression and metastasis. However, we here found that HETEs did not affect the proliferation of melanoma in vitro. This may part
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The evidence points toward a role for
2023-09-27
The evidence points toward a role for 12/15-LO activity in WAT in modulating chronic local inflammation and subsequent systemic metabolic decline in the obese state. However, little is known as to the role of 12- and 15-LOs in BAT. Indeed, in addition to WAT, platelet- and leukocyte-type 12-LO are e
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An issue related to research without biomarkers is that many
2023-09-27
An issue related to research without biomarkers is that many studies will ascertain some but not all biomarker groups in study participants. Because tau PET is relatively new, incomplete biomarker information will occur in studies that use imaging for amyloid and neurodegenerative biomarker characte
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DS2 australia A limitation of the NIA AA recommendations was
2023-09-27
A limitation of the 2011 NIA-AA recommendations was that biomarkers were grouped into just two categories—amyloid and tau-related neurodegeneration. Tauopathy and neurodegeneration were placed into the same biomarker category. In persons with only AD, it is reasonable to assume that neurodegeneratio
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br Conclusion br Acknowledgement This work was supported
2023-09-27
Conclusion Acknowledgement This work was supported by JSPS KAKENHI (Grant Number 15K18770). Introduction Neural crest E3330 are multipotent progenitors in the vertebrate embryo that give rise to a vast array of different cell types including pigment cells, craniofacial skeleton and mesenc
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br Does TIPARP contribute to
2023-09-27
Does TIPARP contribute to the diverse species sensitivity to TCDD toxicity? In chick embryo hepatocytes TIPARP was reported to mediate the TCDD-dependent suppression of hepatic gluconeogenesis, by reducing cellular NAD+ levels and reducing PCK1 expression, suggesting that ADP-ribosylation enhance
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