• We found that decreased Ng levels lead

  2025-01-13

  

  We found that decreased Ng levels lead to a lower threshold for LTD induction at L4–L2/3 synapses. Previous studies in hippocampal slice culture have shown that LTD at individual synapses induces spine elimination at both the targeted synapse and selective neighboring synapses when spines are monito

• br Conclusion We have identified three non competitive inhib

  2025-01-13

  

  Conclusion We have identified three non-competitive inhibitors of the human and porcine APN with Ki values in the μM range, by combining virtual screening and kinetic assays. Molecular docking simulations suggest these novel inhibitors block APN activity by an alternative mechanism to Zn coordina

• The role of the adaptive immune

  2025-01-13

  

  The role of the adaptive immune response in AD is not fully understood and previous studies are controversial. In this context, serum levels of T and B lymphocytes were found to be reduced in AD patients, suggesting a decline of the immune response during the course of the disease (Richartz-Salzburg

• br Conclusion br Conflict of interest br Acknowledgments We

  2025-01-13

  

  Conclusion Conflict of interest Acknowledgments We thank Nancy Kerkvliet for helpful advice. The research in the lab of CE and THS is supported by the Deutsche Forschungsgemeinschaft (grants ES103/7-1 and 9-1, HA7346/2-1). We apologize to all authors whose work could not be cited due to lim

• Our initial approach to identify hits was two pronged

  2025-01-13

  

  Our initial approach to identify hits was two-pronged and included a high-throughput screening (HTS) campaign of the OSI ahr pathway library as well as a virtual screening (VS) campaign, utilizing a publically available crystal structure of ACK1 (PDB code: ). A tolerance for protein flexibility was

• Methylpiperidino pyrazole br Introduction Myasthenia gravis

  2025-01-13

  

  Introduction Myasthenia gravis (MG) is an autoimmune disease in which antibodies against targets on the postsynaptic muscle membrane cause neuromuscular transmission failure. About 85% of patients with MG have autoantibodies against Methylpiperidino pyrazole receptor (AChR) [1]. In AChR negative

• br Free entry equilibrium At stage of the

  2025-01-13

  

  Free entry equilibrium At stage 2 of the game, n ≥ 2 firms simultaneously decide whether or not to enter the industry. Market entry involves a sunk fixed cost f > 0, which we assume cannot be subtracted from the tax base. Our assumption reflects that deductions of market entry costs are often inc

• Introduction The lysosomal storage disorder

  2025-01-13

  

  Introduction The lysosomal storage disorder Gaucher disease (Mendelian Inheritance in Man, OMIM #230800) results from the recessively inherited deficiency of lysosomal glucocerebrosidase (GCase, EC 3.2.1.45), caused by mutations in the gene GBA1 (MIM# 606463) located on chromosome 1q21. The enzymat

• Recent studies demonstrated FoxO a

  2025-01-13

  

  Recent studies demonstrated FoxO3a enhances the protective functions of autophagy in response to environmental stress , . FoxO3a coordinately activates autophagy by binding directly to the promoters of autophagy-related genes, including LC3, Gabarapl1, Beclin1, and Atg12 in atrophied skeletal muscle

• There are profound differences between

  2025-01-10

  

  There are profound differences between acute and chronic pain when dramatic changes occur in peripheral nociceptors and central nociceptive pathways and the pain system is sensitised thereby leading to exaggerated responses to noxious stimuli (hyperalgesia) and responses to non-noxious stimuli (allo

• Another interesting aspect of neutralizing AP is

  2025-01-10

  

  Another interesting aspect of neutralizing AP-1 is the inhibition of interactions between AP-1 and Smad proteins, which synergize to activate the TGF-β1-responsive genes involved in hypertrophic growth of the heart muscle and in the development of cardiac fibrosis. Through preventing AP-1 activation

• br Summary and future br Introduction Androgen activity is

  2025-01-10

  

  Summary and future Introduction Androgen activity is critical for a wide range of developmental and physiological responses and is especially important in male sexual differentiation and maturation. The biological activity of androgens occurs through binding to the androgen receptor (AR) and t

• Introduction Alzheimer s disease AD

  2025-01-10

  

  Introduction Alzheimer's disease (AD) is a complex neurological disorder characterized by a progressive dementia resulting from synapse failure (Selkoe, 2002, Tanzi, 2005). The amyloid hypothesis maintains that the pivotal event in AD is the production of amyloid-β (Aβ) peptides following the prote

• At the organismal level skeletal muscle lung and adipose tis

  2025-01-10

  

  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

• Notably we have characterized the

  2025-01-10

  

  Notably, we have characterized the mechanism of action of ALK in the context of our current understanding of NLRP3 activation [5]. Non-priming macrophages, including BMDMs, exhibit no or minimal activation of NLRP3 in response to ATP. In contrast, LPS priming of macrophages makes them highly suscept

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