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The increased occurrence of ARIA
2024-08-19
The increased occurrence of ARIA-E in APOE ε4 carriers in phase 2 studies resulted in separate protocols for carriers and noncarriers in the subsequent phase 3 studies. Two 18-month trials comprising 1121 carriers and 1331 noncarriers with mild to moderate AD tested doses of bapineuzumab that varied
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To guide our attempts at achieving AKT potency
2024-08-17
To guide our attempts at achieving AKT potency and selectivity against p70S6K and other kinases from (p70 S6K IC: 0.004 μM) and , we took advantage of exploiting the subtle sequence differences in the active sites of the AGC family kinases, we utilized the information around crystal structure of AKT
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An alternative approach to the administration of ADO agonist
2024-08-17
An alternative approach to the administration of ADO agonists is to amplify the actions of endogenous ADO by inhibiting the ADO-metabolizing enzyme, ADO kinase (AK). Inhibition of AK has the net effect of potentiating the local concentration and the effects of ADO in the extracellular compartment. T
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br Introduction In myasthenia gravis
2024-08-17
Introduction In myasthenia gravis (MG), autoantibodies against the native AChR conformation cause loss of AChR at the neuromuscular junction and fatigable muscle weakness (Newsom-Davis et al., 1993). The AChR is a pentameric transmembrane protein, with two splice forms of the α-subunit, P3A− and
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Fmoc-Phe-OPfp australia Since the localization of LO
2024-08-17
Since the localization of 5-LO depends on phosphorylation, we also analyzed the phosphorylation profile of 5-LO-WT and all isoforms by Western blot using specific Fmoc-Phe-OPfp australia against the phosphorylation sites S271 and S523. Whereas phosphorylation at S271 activates the 5-LO, inhibits nu
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It is reported that calpain
2024-08-17
It is reported that calpain-2 plays a critical role in BDNF-induced signaling and memory formation, and knockdown of calpain-2, but not calpain-1, completely suppresses BDNF-induced pathway activation and protein translation (Briz et al., 2013). BDNF prevents neuronal apoptosis or death (Ferrer et a
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Despite clear evidence of a causative role for A in
2024-08-16
Despite clear evidence of a causative role for Aβ in AD, Aβ-mediated toxicity alone is insufficient to explain all facets of fully manifested AD. Indeed, a recent report found that two familial AD mutations in PSEN1, PSEN-L435F and PSEN-C410Y, resulted in a dysfunctional protein that does not cleave
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At the organismal level skeletal muscle lung and
2024-08-16
At the organismal level, skeletal muscle, lung and adipose tissues mediate net de novo synthesis and release of glutamine, whereas net glutamine catabolism occurs in the kidney [7]. The liver exhibits net glutamine consumption coupled to urea production in the post-absorptive state, and net glutamin
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In the QFP rs T
2024-08-16
In the QFP, rs2269657-T allele showed a significant correlation with reduced plaque density in frontal cortices (Table 2), strengthening the association with amyloid pathology. The same 961 region was shown to exhibit a statistically significant reduction of SREBF2 mRNA levels in rs2269657-T carrie
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In summary we identified a novel
2024-08-16
In summary, we identified a novel MLPH-ALK fusion in AST with discordant results of ALK IHC. In order not to overlook ALK-rearranged AST with rare fusion partners on IHC screening, a sensitive IHC method is preferable. Introduction Lung cancer remains the leading cause of cancer related deaths w
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Nrf br AhR br Nrf
2024-08-16
Nrf2 AhR Nrf2 and AhR: friends or foes for energetic metabolism? Perspectives in carcinogenesis upon xenobiotic exposure Acknowledgements Introduction Integration of endogenous and exogenous signals via appropriate receptors is at the core of biological differentiation and adaptive r
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br Adenosine receptors and innate immunity Monocytes and mac
2024-08-16
Adenosine receptors and innate immunity Monocytes and macrophages. All four adenosine receptor subtypes are expressed on monocytes and macrophages, and their levels and function undergo significant changes during the maturation of macrophages from monocytes. Indeed, quiescent monocytes are charac
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Given the powerful and ubiquitous
2024-08-16
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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Furthermore our lab previously reported
2024-08-16
Furthermore, our lab previously reported that cadmium treatment increased AChE-S and decreased AChE-R variants gene expression, which mediates the cell death observed on basal forebrain cholinergic neurons (Del Pino et al., 2016b). AChE-R decreased expression, which presents a neuroprotective role i
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To date more than different mutations
2024-08-16
To date, more than 50 different mutations in the gene have been described (Human Gene Mutation Database at the Institute of Medical Genetics in Cardiff: SRD5A2 Gene: http://www.hgmd.cf.ac.uk). Most of them are missense mutations but premature stop codons and deletions leading to non-functional or su
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