• Having established the structural requirements for potency

  2023-03-27

  

  Having established the structural requirements for potency in both the biochemical and biomarker (CRA) assays, we evaluated key compounds in the metabolic stability assay. Disappointingly, we found that all compounds had high intrinsic clearances in mouse microsomes. To ascertain whether the in vitr

• We also show that in both ATM proficient

  2023-03-27

  

  We also show that in both ATM proficient and deficient/mutant A 205804 synthesis the activation of ATR signaling is DSB complexity-dependent (Figs. 1, 4A, C and E, 6A and B). Wang et al. have also reported that the effects of ATR and CHK1 on radiosensitivity are independent of the NHEJ repair pathw

• It has also been reported that defects

  2023-03-27

  

  It has also been reported that defects in ATM or ATR signalling are synthetically lethal with PARP inhibition (Turner et al., 2008, Peasland et al., 2011, Yap et al., 2011, Michels et al., 2014), suggesting that combined inhibition of PARP and ATM or ATR may be an effective therapeutic strategy. In

• Because ASK signaling in microglia and

  2023-03-27

  

  Because ASK1 signaling in microglia and astrocytes is important during EAE, we hypothesized that a combination therapy that targets T cells along with microglia and astrocytes would further ameliorate the severity of EAE. We tested this hypothesis by applying valproic Bufalin (VPA)—a short-chain fat

• br Introduction Hepatocellular carcinoma HCC is an

  2023-03-27

  

  Introduction Hepatocellular carcinoma (HCC) is an aggressive and malignant cancer detected in clinical practice, as it is the third key reason of tumor-related deaths worldwide, with > 800, 000 mortalities every year (Torre et al., 2015). Current treatments for HCC are surgical therapy, liver tra

• Several strategies have been employed to

  2023-03-25

  

  Several strategies have been employed to design and engineer peptide biosensors of kinase activity, which are quite different from the strategies developed to generate genetically encoded KARs. In all cases, cisapride induces changes in the spectral properties of the fluorophore(s) incorporated int

• br STAR Methods br AMPK A

  2023-03-23

  

  STAR★Methods AMPK: A Therapeutic Target in the β Cell? Loss of pancreatic β cell function is a hallmark of the transition to a diagnosis of T2DM (see Glossary) 1, 2, 3, 4. AMPK activation has gained attention for the treatment of hyperglycemia in prediabetes as an insulin-sensitizing agent bec

• br STAR Methods br AMPK A

  2023-03-23

  

  STAR★Methods AMPK: A Therapeutic Target in the β Cell? Loss of pancreatic β cell function is a hallmark of the transition to a diagnosis of T2DM (see Glossary) 1, 2, 3, 4. AMPK activation has gained attention for the treatment of hyperglycemia in prediabetes as an insulin-sensitizing agent bec

• Histochemical analyses using antibody or cDNA

  2023-03-22

  

  Histochemical analyses using antibody or cDNA probes reveal the precise cellular location of the 12S-lipoxygenases in tissues of interest. An immunohistochemical study in various rat tissues showed specific expression of the leukocyte-type 12S-lipoxygenase in macrophages in lung and spleen [27]. In

• Additionally we were prompted to validate the protective eff

  2023-03-22

  

  Additionally, we were prompted to validate the protective effect of ALDH3A1 by utilizing a human corneal model. Cornea is located in the anterior segment of the eye and thus, is constantly exposed to various environmental stressors that affect the cellular oxidative balance and consequently lead to

• br Funding This work was supported by

  2023-03-22

  

  Funding This work was supported by Arena Pharmaceuticals, Inc, San Diego, CA, USA. Introduction 5-hydroxytryptamine 1B (5-HT1B) receptors are widely distributed in the central nervous system (CNS); they have various modulatory functions in drug reinforcement, appetitive behaviors, stress, moo

• Neural progenitor cells NPCs are

  2023-03-22

  

  Neural progenitor cells (NPCs) are self-renewing, multipotent cells that are capable of differentiating into neurons, astrocytes and oligodendrocytes. NPCs are activated in response to a variety of pathological states in neurodegenerative diseases such as Parkinson’s disease and multiple sclerosis,

• Introduction Adenosine kinase ADK ATP adenosine phosphotrans

  2023-03-22

  

  Introduction Adenosine kinase (ADK; ATP: adenosine 5′-phosphotransferase, EC 2.7.1.20), is isolated from yeast cells by Kornberg for the first time in 1951 [1]. ADK belongs to the ribokinase protein family and is one of the most abundant nucleoside kinases in mammalian tissues [2,3]. As the first i

• br GMF Remodels Actin Networks

  2023-03-22

  

  GMF Remodels Actin Networks at the Leading Edge How are the conserved activities of GMF used in vivo to regulate branched Neuropeptide Y 13-36 (porcine) networks (e.g., at sites of endocytosis and at the leading edge) (Figure 2A,B)? In animal cells, the regulatory effects of GMF on actin network

• br Mechanisms of specific immunotherapy Several mechanisms m

  2023-03-22

  

  Mechanisms of specific immunotherapy Several mechanisms may be involved in specific immunotherapy of EAMG by active immunization with the therapeutic vaccine in IFA. During the therapy, the therapeutic benefits result from diversion of autoantibody specificities away from pathogenic extracellular

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