• We designed SSOs that block APP exon splicing

  2024-03-22

  

  We designed SSOs that block APP exon 17 splicing and induce the production of an alternatively spliced APP mRNA lacking exon 17 (APPΔex17). APPΔex17 mRNA encodes an APP protein isoform that lacks 49 fg 4592 including the γ-secretase cleavage sites that give rise to the toxic, AD-associated Aβ42 pep

• At the top of the

  2024-03-22

  

  At the top of the S1 subsite cylinder are two “cap” residues: E572 and M1034 [13]. Atomic structures of PfA-M1 have revealed important clues into potential roles for the cap residues in substrate selection. In the PfA-M1:bestatin co-crystal structure ([13]; Fig. 1), the P1 phenyl ring occupies the S

• br Disclosure br Acknowledgments br Introduction Deeper unde

  2024-03-22

  

  Disclosure Acknowledgments Introduction Deeper understanding of the pathobiology of non-small cell lung cancer (NSCLC) has led to the development of small Manumycin A that target genetic mutations known to play critical roles in the progression to metastatic disease. Mutations in epidermal

• br Mechanisms for regulation of intracellular cholesterol

  2024-03-21

  

  Mechanisms for regulation of intracellular cholesterol homeostasis Cells maintain intracellular free cholesterol levels and distribution within stringent tolerances by several mechanisms [55]: (1) uptake of native LDL (the major extracellular carrier of cholesterol) by LDL receptors and modified

• Adiponectin also works on AdipoR

  2024-03-21

  

  Adiponectin also works on AdipoR1, inducing extracellular Ca2+ influx necessary for activation of Ca2+/calmodulin-dependent protein kinase kinase (CaMKK)β, AMPK (Fig. 1). This step is then followed by activation of SirT1 and increased expression and decreased acetylation of PPARγ coactivator (PGC)-1

• APPL is highly expressed in pancreatic cells but

  2024-03-21

  

  APPL1 is highly expressed in pancreatic β cells, but its levels are significantly decreased in several mouse models of obesity and diabetes, including HFD-induced obese mice and db/db mice [6], [73], suggesting that the dysregulation of APPL1 may be associated with malfunction of the pancreas in obe

• We also demonstrate that PACAP treatment dose dependently

  2024-03-21

  

  We also demonstrate that PACAP treatment dose-dependently disrupts performance in the 5CSRTT, suggestive of attentional deficits, another core feature of mood and anxiety disorders. Treatment with PACAP (.5–1.0 µg) decreased the percentage of correct responses, increased the percentage of trials in

• Toxicity is the main reason for the

  2024-03-21

  

  Toxicity is the main reason for the failure at all stages of the new drug development process. The major part of safety-related attrition occurs at preclinical phases while predicting preclinical safety liabilities earlier in the drug development process. This strategy enables the design and/or sele

• br Results and discussion br Conclusion A series of aminoben

  2024-03-21

  

  Results and discussion Conclusion A series of aminobenzothiazole derivatives were investigated as possible Aurora B kinase inhibitors. Bioisosteric replacement of the heterocyclic core of the lead compound was performed regarding the docking analysis. Replacement of the oxygen JNJ-26481585 of

• Neuropathic animals display increased sensitivity to the

  2024-03-21

  

  Neuropathic animals display increased sensitivity to the anti-nociceptive effect of baclofen and whilst the number and affinity of GABAB Donitriptan hydrochloride in the dorsal horn are not altered (Smith et al., 1994; Zemoura et al., 2016), GABAB receptors subunits (B1 and B2) are both down-regula

• br Introduction Arginase deficiency is a rare metabolic diso

  2024-03-21

  

  Introduction Arginase deficiency is a rare metabolic disorder resulting from a loss of arginase 1 (ARG1), the final enzyme in the urea cycle, which is the major pathway for the detoxification of ammonia in terrestrial mammals. ARG1 is expressed most prevalently in hepatocytes and red blood cells.

• Chlorogenic acid an abundant polyphenol found in coffee and

  2024-03-21

  

  Chlorogenic 67 7 (7), an abundant polyphenol found in coffee and the human diet, has various biological activities including antioxidant and anticancer effects [54]. Jiang et al. reported that compound 7 had a selective cytotoxic activity on human oral tumor cells (HSG, HSC-2) as compared with norma

• br Consequences of central apelin

  2024-03-21

  

  Consequences of central apelin/APJ modulation Regarding extra-hypothalamic actions, recent data demonstrate that the central apelin/APJ system could be a potential new target for the regulation of memory (Han et al., 2014). Then, intracerebroventricular (icv) apelin administration in mice impairs

• In this study we have

  2024-03-20

  

  In this study, we have generated new FRET reporters to screen all submembrane domains of AT1R for interactions with CaM. We identified a new CaM-binding domain on the receptor’s SMD2 (a.a. 125 – 141), confirmed interactions at SMD4JM (a.a. 309 – 327) and characterized the full interacting domain in

• In our study we provide evidence for

  2024-03-20

  

  In our study we provide evidence for the existence of an endosome-lysosomal pathway for the proteolytic degradation of AR triggered by its interaction with the ESCRT-I component TSG101. The following findings of this study support this notion: (1) We showed that TS101 interacts with endogenous or ec

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