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The overall mechanism of the Cdc complex
2023-01-30

The overall mechanism of the Cdc48 complex resembles that of the 19S regulatory subunit of the proteasome, which also uses receptor proteins to bind polyubiquitin chains attached to a substrate and employs a translocation mechanism (for review, see Kish-Trier and Hill, 2013). As with Cdc48, full sub
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Hyperactivity of the hypothalamus pituitary
2023-01-29

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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Imaging QTL studies may have
2023-01-29

Imaging QTL studies may have several potential advantages over case-control studies, including increased power . Imaging endophenotypes of disease in QTL studies can separate patients and normal subjects more accurately and therefore limit the confound of including asymptomatic subjects in the contr
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br Disclosure br Acknowledgments br Introduction Deeper
2023-01-29

Disclosure Acknowledgments Introduction Deeper understanding of the pathobiology of non-small cell lung cancer (NSCLC) has led to the development of small Ch 55 that target genetic mutations known to play critical roles in the progression to metastatic disease. Mutations in epidermal growt
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Mechanistically NAergic signaling in the VTA modulates neuro
2023-01-29

Mechanistically, NAergic signaling in the VTA modulates neuronal activity presumably via α1-AR. The majority of α1-ARs are found in the VTA are located presynaptically on unmyelinated PKR Inhibitor synthesis and axon terminals of glutamatergic and GABAergic neurons. However, α1-ARs are also found o
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In the late s Solvay Pharmaceuticals discontinued the Phase
2023-01-29

In the late ‘90s, Solvay Pharmaceuticals discontinued the Phase 2 development of a promising potent and highly selective A1AR antagonist based on the pyrrolopyrimidine scaffold, SLV320 [43] (2, Chart 1, also named derenofylline; Ki hA1AR = 1 nM), for the treatment of acute heart failure [24]. In the
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AdK as an important upstream regulator of adenosine
2023-01-29

AdK as an important upstream regulator of adenosine-based homeostasis represents a promising drug target since it leads to an increase in adenosine concentrations. Taking into account that the adenosine formation is only increased in affected tissues under stress with high adenosine levels, AdK inhi
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br Results br Discussion Today enzymes play
2023-01-29

Results Discussion Today, enzymes play important roles in various fields. A good assay for enzyme activity is of great value, especially when it has good specificity, sensitivity, reproducibility and economy. ADK is the first identified enzyme in the metabolic pathway of adenosine salvage [15,
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Axl has been reported to mediate
2023-01-29

Axl has been reported to mediate cell-cell adhesion and sphere-growth [11], [18] and to be important for metastasis to secondary organs [12], [14], [20]. We found an Axl-dependent CCRCC-ability of sphere-formation and repopulation after non-adhesive growth. Axl-inhibited cells could not attach to ea
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Upregulation of ACLY is common in many cancers Kuhajda
2023-01-29

Upregulation of ACLY is common in many cancers (Kuhajda, 2000, Milgraum et al., 1997, Swinnen et al., 2004, Yahagi et al., 2005). This is in part due to the transcriptional activation by SREBP-1 resulting from the activation of the PI3K/AKT pathway in cancers (Kim et al., 2010, Nadler et al., 2001,
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Several alterations have been or can be associated to
2023-01-29

Several alterations have been or can be associated to the decreased tolerance of steatotic liver to I/R injury. Previous studies demonstrated that upregulation of the mitochondrial uncoupling protein-2 (UP2) is strictly related to the increase of I/R injury in steatotic liver [4]. UPR induction is c
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It is well known that neurosteroids such
2023-01-29

It is well-known that neurosteroids such as testosterone and their metabolites endogenously modulate neural excitability in animals and humans. Testosterone has protective effects against seizures induced by KA and PTZ (Frye et al., 2001b; Reddy, 2004b). Estrogens, on the other hand, have proconvuls
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gamma-Secretase inhibitor IX Of the cardiovascular studies i
2023-01-29

Of the cardiovascular studies involving ARBs, 3 reported renal outcomes. In the Losartan Intervention For Endpoint study, albuminuria was observed less frequently in the losartan than in the atenolol arm (7% vs. 13%; p=0.002) (5). In the Candesartan Antihypertensive Survival Evaluation in Japan tria
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The expanding catalog of glutamate receptor auxiliary subuni
2023-01-28

The expanding catalog of glutamate receptor auxiliary subunits and associated transmembrane proteins underscores the importance and complexity of the receptor complexes. Whereas the interactions described here specifically control AMPARs, distinct auxiliary subunits, Neto-1/2, modulate neuronal kain
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Several ceritinib resistant mutations following the second l
2023-01-28

Several ceritinib-resistant mutations following the second-line treatment of ALK+-NSCLC have been discovered [64]. These mutations include C1156Y, F1174L, and L1152R, which were first observed in crizotinib-resistant tumor samples. The G1202R ceritinib-resistant mutation occurs within the hinge and
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