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During the course of our ACK
2023-12-13
During the course of our ACK1 inhibitor program, a high-throughput screening (HTS) campaign of our internal sample collection was conducted. A series of -aryl pyrimidine-5-carboxamides of the general structure () was identified. Earlier studies of the structure–activity relationship (SAR) of ident
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In the previous study we demonstrated the importance of the
2023-12-12
In the previous study, we demonstrated the importance of the mPFC postsynaptic 5-HT1A receptor in the sustained antidepressant effects, because a sustained antidepressant effect was obtained with intra-mPFC injection, but not systemic injection of 8-OH-DPAT, a 5-HT1A receptor agonist (Fukumoto et al
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In the last decade the zebrafish has emerged as a
2023-12-12
In the last decade, the zebrafish has emerged as a valuable vertebrate model to systematically dissect the genetic underpinnings of both vertebrate heart development and function [8,9], as well as distinct cardiac diseases such as congenital heart disease [10], cardiomyopathies [11,12] and cardiac
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br Results br Discussion br Conclusion
2023-12-12
Results Discussion Conclusion The flux of glucose into cytosolic short chain acyl-CoAs was maintained in pure beta Losartan sale in the presence of inhibition of ATP citrate lyase with hydroxycitrate and also in a cell line with >90% ATP citrate lyase knockdown suggesting that a pathway ot
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Songbirds are outstanding models in the study of vocal
2023-12-12
Songbirds are outstanding models in the study of vocal communication (Maney and Pinaud, 2011). Following the pioneering studies of William H. Thorpe and Peter Marler on the development of song in chaffinches (Fringilla coelebs) and white-crowned sparrows (Zonotrichia leucophrys) (Marler, 2004; Thorp
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br Future view and implications
2023-12-12
Future view and implications The selection and spread of multi(drug)-resistant microorganisms over the last decades has become a major and global public health concern [35]. Two growing threats originating from the fungal kingdom, i.e. Aspergillus fumigatus and Candida auris[36], [37], re-emphasi
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br Future directions outlook Peptide based macrocycles are a
2023-12-12
Future directions-outlook Peptide-based macrocycles are among the privileged scaffolds in antibiotic drug discovery. Many compounds were discovered by natural product screening and developed unchanged, or as semi-synthetic derivatizations. Since the golden age of antibiotic discovery (1940s-mid 1
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Introduction It has long been recognized that
2023-12-12
Introduction It has long been recognized that angiogenesis is critical to the growth, progression, and metastasis of many solid tumor types [1], and thus, drugs targeting the angiogenic pathway have been a topic of clinical investigation in the oncology community for many years. Angiogenesis is reg
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tezacaftor In our sequential model for tau
2023-12-12
In our sequential model for tau and Aβ deposition, we included the tau deposition in the medial temporal tezacaftor 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
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Ultracentrifugation of AD brain was reported
2023-12-12
Ultracentrifugation of AD I-BET151 was reported to remove >99.95% of Aβ, while only reducing seeding capacity by 70% (Langer et al., 2011). This suggests that the most potent seeding Aβ species are relatively small soluble oligomers rather than larger insoluble fibrils. It was also noted that this
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br Pathophysiology of Alzheimer disease Alzheimer disease is
2023-12-12
Pathophysiology of Alzheimer disease Alzheimer disease is characterized by severe neurodegeneration, neuroinflammation, and progressive loss of cognitive abilities. The diagnostic criteria for dementia released by the National Institute on Aging-Alzheimer's Association define dementia as the deve
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br Special report Financial and personal benefits of
2023-12-12
Special report – Financial and personal benefits of early diagnosis Acknowledgments The Alzheimer’s Association acknowledges the contributions of Joseph Gaugler, Ph.D., Bryan James, Ph.D., Tricia Johnson, Ph.D., Allison Marin, Ph.D., and Jennifer Weuve, M.P.H., Sc.D., in the preparation of 201
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Introduction Aldose reductase ALR is the first enzyme of
2023-12-12
Introduction Aldose reductase (ALR2) is the first enzyme of the polyol pathway that catalyzes the reduction of glucose to sorbitol utilizing NADPH as a cofactor. The intracellular accumulation of sorbitol, due to increased aldose reductase activity at high blood glucose levels, such as those occurr
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br Functions essentially consisting in transport of substrat
2023-12-12
Functions essentially consisting in transport of substrates across plasma membranes Direct activation of neurotransmitter transporters elicits responses in neurons As previously mentioned (Section 2.1), nerve terminals handling classical transmitters possess transporters able to (re)capture se
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A key step in the ADAR reaction is the formation
2023-12-11
A key step in the ADAR reaction is the formation of the adenosine covalent hydrate with a tetrahedral center at C6. The nucleoside analog 8-azanebularine (box in Fig. 6), with its relatively high propensity to form a covalent hydrate, is useful as an adenosine replacement in ADAR2 substrates to trap
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