• Activated MAP kinases transform the stimulus into the

  2024-03-18

  

  Activated MAP kinases transform the stimulus into the pathophysiological responses by phosphorylating downstream substrates, including transcription factors, cytoskeletal proteins involved in mRNA translation (Li et al., 2015). Among the numerous effectors that intervene in the TNF-α action is an ac

• br Experimental section br Acknowledgements br Introduction

  2024-03-18

  

  Experimental section Acknowledgements Introduction DJ-1 is a highly conserved, homodimeric protein that was originally cloned as an oncogene capable of transforming LDN 57444 in cooperation with activated ras[1]. DJ-1 is over-expressed in multiple tumor types and is positively correlated w

• Arginase deficiency is a rare

  2024-03-18

  

  Arginase deficiency is a rare urea cycle disorder with hyperargininemia and profound neurological impairment as hallmark features. Arginase-1-deficient mouse models have been created, and they exhibit a profound lethal phenotype approximately 2 weeks after birth in the global knockout (KO) mice or a

• Weak and transient interactions of HMGB

  2024-03-18

  

  Weak and transient interactions of HMGB proteins in such hit-and-run mechanisms are understandable given that “fluorescence loss in photobleaching” (FLIP) experiments employing GFP-labeled HMGBs have shown that in living cells they are the most mobile of all nuclear proteins [144]. The entire pool o

• The loss of synaptic proteins such as

  2024-03-18

  

  The loss of synaptic proteins such as synaptophysin from the Protease Inhibitor Cocktail (EDTA-Free, 100X in DMSO) is indicative of synapse degeneration and provided a good correlate of the degree of dementia in AD [12], [13], [14]. Consequently, the loss of synaptic proteins from cultured primary n

• br Materials and methods br Results br Discussion Endophilin

  2024-03-18

  

  Materials and methods Results Discussion Endophilin A1 is a membrane-binding protein that is mainly distributed in the central nervous system (Giachino et al., 1997), localizes in the dendritic shafts and spines of mature neurons (Yang et al., 2015), and relates to the function and morpholo

• br We approached the definition of AD with the distinction

  2024-03-18

  

  We approached the definition of AD with the distinction between a syndrome and a disease in mind. Some will argue that a specific syndrome, that is, a multidomain amnestic dementia (after other potential etiologies have been excluded), should define AD in living people. Our position, however, is t

• In this study we designed and synthesized two ALK PROTACs

  2024-03-18

  

  In this study, we designed and synthesized two ALK PROTACs (degraders), 5 (MS4077) and 6 (MS4078), by linking ceritinib and pomalidomide [45] through two different linkers. Using human ALCL and NSCLC cells, we characterized both compounds in a battery of assays to demonstrate their effects on reduci

• Glucose Uptake Fluorometric Assay Kit receptor br Conflict o

  2024-03-18

  

  Conflict of interest statement Introduction Currently, adenocarcinoma is the most common histological subtype of lung cancer. Activating mutations and translocations with a potential for targeted therapy are reported predominantly in non-smokers. ALK rearrangement is found in less than 5% of u

• Liver plays a pivotal role in

  2024-03-18

  

  Liver plays a pivotal role in metabolism of xenobiotic compounds, such as environmental contaminants and drugs. Some of these compounds generate hepatic damage and impair its function. It was well-known that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) could induce pathological changes in mouse and ra

• br Material and methods br Results br Discussion GRK

  2024-03-18

  

  Material and methods Results Discussion GRK2 activity has increasingly been shown to contribute to the progression of numerous diseases and organ dysfunction [5], [6]. For instance, a large body of work over the last two decades has identified GRK2 as a major regulator of cardiac dysfunctio

• Given these findings above we hypothesized that hypernocicep

  2024-03-18

  

  Given these findings above, we hypothesized that hypernociception produced by intra-amygdala 8-OH-DPAT is result of hyperpolarization in this area. This neuronal inhibition of the amygdaloid complex might result in an inactivation of crucial neurotransmitter systems of the descending inhibitory pain

• br Conflict of interest br Acknowledgments This work was sup

  2024-03-16

  

  Conflict of interest Acknowledgments This work was supported by research grant [PR26/20326] from Santander Bank/UCM. The authors would like to thank Miguel Capo, Professor of Toxicology from the Universidad Complutense de Madrid, for his counseling during the preparation of the present work.

• br Acknowledgment br Introduction The

  2024-03-16

  

  Acknowledgment Introduction The yeast Cdc48 ATPase and its metazoan ortholog p97 (or VCP) are critical components of many ubiquitin-dependent cellular pathways that require the segregation of individual proteins from binding partners or membranes (for review, see Buchberger, 2013, Meyer and We

• Based on the extracellular domain structures we can infer th

  2024-03-16

  

  Based on the extracellular domain structures, we can infer that the dimer arrangement of GABAB receptor will undergo substantial changes upon receptor activation (Geng et al., 2013). First, agonist-stimulated closure of GABAB1 VFT would cause an upward rotation of its LB2 domain, coupled with an inw

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