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In the largest postmortem study of autopsied individuals alm
2025-01-27
In the largest postmortem study of 3618 autopsied individuals, almost 75% of the individuals without Aβ pathology already harbored cortical NFT pathology mostly confined to the medial temporal regions (Murray et al., 2015). In Braak's study of 2366 autopsied individuals (Braak and Del Tredici, 2014
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Inhibition of autophagy has been shown to alleviate
2025-01-27
Inhibition of autophagy has been shown to alleviate neuronal damage after cerebral ischemia, both in cell culture and rodent models (Koike et al., 2008, Li et al., 2015, Wang et al., 2016, Zhang et al., 2014, Zheng et al., 2014). Therefore, blockage of autophagy is a potential target for prevention
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br Perspectives br Acknowledgments This
2025-01-27
Perspectives Acknowledgments This investigation was supported by a Research Grant 2010/01385-5 from FAPESP (Sao Paulo Research Foundation, Brazil). P.F.S. was recipient of a CNPq (National Council for Scientific and Technological Development, Brazil) productivity grant. R.F.A. was recipient of
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br Development of lorlatinib from crizotinib to
2025-01-26
Development of lorlatinib from crizotinib (1) to a clinical candidate (6) Xalkori (1, PF-02341066, crizotinib), was the first-in-class ALK inhibitor approved by the Unites States Food and Drug Administration (FDA) in 2011 as a first-line treatment for ALK+- NSCLC patients. This section describes
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The random zero offset of accelerometer and gyroscope
2025-01-26
The random zero offset of accelerometer and gyroscope estimated by two-step observation update Kalman filter are shown in Table 2, one group of estimated results is shown in Fig. 3. Contrast with the data from Eq. (23) and the ones from Fig. 3 and Table 2, it can be seen that the random zero offset
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The present work has implications for our thinking about the
2025-01-26
The present work has implications for our thinking about the effects of antidepressant (e.g. SSRIs) use on maternal care in depressed mothers which consist of approximately 10–20% of all mothers (Gjerdingen and Yawn, 2007, Susser et al., 2016), and more than 40% of depressed mothers are prescribed w
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br There is evidence to suggest that GMF activities
2025-01-26
There is evidence to suggest that GMF activities are regulated in vivo by post-translational modification. indeed, there is strong precedent for ADF-homology family proteins being regulated in this manner. Cofilin is inhibited by phosphorylation of a serine residue at its N terminus. This residue
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br Acknowledgments br Introduction Hypospadias is a
2025-01-26
Acknowledgments Introduction Hypospadias is a common congenital malformation in males, in which the urethral orifice is found on the ventral side of the penis as a result of incomplete fusion of urethral folds. The mean prevalence in per 10,000 live births from 1910 to 2013 were: Europe 19.9,
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In conclusion we have produced
2025-01-26
In conclusion, we have produced some highly potent inhibitors of P450 in comparison to the standard mGlu receptor agonist KTZ. Also, due to the limited specificity of these compounds against lyase in comparison to the 17α-OHase component, these compounds would be expected to have a major impact on
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Double immunofluorescence staining of Gas and Axl
2025-01-26
Double immunofluorescence staining of Gas6 and Axl with neuronal specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba-1), demonstrated that Gas6 and Axl are expressed by neurons, astrocytes and microglia/macrophages (Fig. 2). In
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The ATX LPA signaling axis has been implicated in a
2025-01-26
The ATX–LPA signaling “axis” [5] has been implicated in a perplexing variety of physiological and pathophysiological processes, including vascular and neural development [5], [26], [27], [28], [29], tumor progression and metastasis [30], [31], lymphocyte trafficking [22], bone development [32], neur
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In our previous report we synthesized derivatives with some
2025-01-26
In our previous report, we synthesized derivatives with some straight chain residues on the 2-position of the 3-cyanopyridine ring of compound 1. In this time we tried to introduce aromatic ring on the chain of the 2-position. Namely, we replaced the hydroxyl-alkylamino group in the position 2 of t
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If the lack of specificity and the high pleiotropy
2025-01-26
If the lack of specificity and the high pleiotropy may represent a problem in view of the potential chemotherapeutic features of autophagy-inducing agents, it Sulindac sulfone may switch into an advantage in the case of chemopreventive strategies. In fact, as non-pharmacologic interventions such as
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GX-674 synthesis Screening a selection of analogues from thi
2025-01-26
Screening a selection of analogues from this library against the panel of 26 kinases (16, 22, and 24 were screened at 30 μM due to poor solubility; 17 tested at 100 μM) generally demonstrated an increase in activity compared to GX-674 synthesis 3 (Fig. 3, Fig. 6). The benzamide analogue 16 demonstr
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The resolution cocrystal structure of ACL in complex with ci
2025-01-26
The 2.10Å resolution cocrystal structure of ACL in complex with citrate indicates that the carboxyl (COH) groups of citrate forms a network of H-bonds with hydrophilic residues surrounding the ACL citrate binding domain (CBD) (A). The - carboxyl group forms a salt bridge with the guanidine moiety of
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