• br Functional repercussions of each trimming pathway A main

  2023-10-10

  

  Functional repercussions of each trimming pathway A main difference between the two pathways presented in Fig. 1 lies in enzyme kinetics and selectivity. In pathway #1, the substrate for ERAP1 is free peptide, and so both kinetics and selectivity are determined by interactions between the peptide

• Interestingly hypoxia and an enhanced Warburg effect ultimat

  2023-10-10

  

  Interestingly, hypoxia and an enhanced Warburg effect ultimately lead to increased lactate production. The accumulation of lactate results in an acidic tumor microenvironment, which induces local inflammation. Lactate also promotes the polarization of macrophages that express immunosuppressive argin

• Despite these efforts to prevent oxidative metabolic degrada

  2023-10-09

  

  Despite these efforts to prevent oxidative metabolic degradation, and showed only marginal improvements in metabolic stability and still exhibited high plasma clearances as shown in . High molecular weight as well as relative high log values could be contributing factors to the poor PK profiles of a

• br ACK inhibitors Since ACK activation is correlated

  2023-10-09

  

  ACK1 inhibitors Since ACK1 activation is correlated with poor prognosis in various cancers, strong efforts are being directed by multiple groups towards developing highly potent and specific small molecule inhibitors targeting the ACK1 kinase. At least eight small molecule kinase inhibitors have

• br Conclusion br Conflicts of

  2023-10-09

  

  Conclusion Conflicts of Interest/Disclosures Acknowledgement This study was funded by the Ministry of Science of the Republic of Serbia (grant #175083). Introduction Myasthenia gravis (MG) is an antibody-mediated, neuromuscular transmission disorder, where the targets are postsynaptic p

• A combination of factors might however

  2023-10-09

  

  A combination of factors might, however, account for the low rate of success of drug development for neuropsychiatric disorders. First, in most neuropsychiatric disorders, the symptomatology is heterogeneous and the neurobiology remains poorly understood, making therapeutic targets difficult to iden

• Among the AXL positive tumors that we

  2023-10-09

  

  Among the AXL-positive tumors that we screened, the TNBC cell line MDA-MB-231 showed the highest AXL expression level. Additionally, AXL protein levels were higher in TNBC patient samples than in other breast cancers. Considering the difficulty of, and the urgent need for, effective treatments of TN

• br Acknowledgements We thank Dr Stefan Schulte Merker and hi

  2023-10-09

  

  Acknowledgements We thank Dr. Stefan Schulte-Merker and his group members at the Hubrecht Institute (Utrecht, the Netherlands) for their invaluable support of the zebrafish studies. Our work is supported by grants from the Dutch Cancer Society (KWF) and the Netherlands Organisation for Scientific

• Crohn s disease an inflammatory bowel disease that

  2023-10-09

  

  Crohn’s disease, an inflammatory bowel disease that affects the gastrointestinal (GI) tract, is characterized by a polymorphism in ULK1 autophagy gene due to the presence of single nucleotide polymorphisms (SNPs). Thus, the autophagic process is impaired during the disease. The mutations in the leuc

• Another topic for research will

  2023-10-09

  

  Another topic for research will be the combination of other cytotoxic agents with Aurora kinase inhibitors. Particularly interesting might be the combination of Aurora kinase inhibitors and agents that depend on the spindle checkpoint for their activity, such as the taxanes, given the importance of

• In liver the essential organ

  2023-10-09

  

  In liver, the essential organ of lipoprotein synthesis, ACL plays a fundamental role in lipogenesis and steroidogenesis by supplying cytosolic 624 to both pathways. By using a tricarboxylic acid cycle intermediate (citrate) to produce acetyl CoA, ACL can be seen as an important bridge between carbo

• br Experimental and simulation section br Acknowledgments Fi

  2023-10-09

  

  Experimental and simulation section Acknowledgments Financial support for this work was provided by the National Natural Science Foundation of China (No. 81101688). We would like to thank NC State University High Performance Computing Center for providing us computing resources, and Dr. Lihui

• br Materials and methods br Results br

  2023-10-09

  

  Materials and methods Results Discussion Japanese encephalitis caused by JEV is characterized by lasofoxifene neuron death. However, the underlying mechanism is not fully understood. We and other researchers have demonstrated that JEV induces apoptosis by ER stress-mediated IRE1/JNK and RO

• br Conflict of interest br Acknowledgment The authors

  2023-10-09

  

  Conflict of interest Acknowledgment The authors gratefully acknowledge the financial support from the National Natural Sciences Foundation of China (81070220 and 81170278), and the Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Human Provi

• We have shown that an extensive region in SERBP amino

  2023-10-09

  

  We have shown that an extensive region in SERBP1 (amino acids 354 to 474, using co-ordinates based on the full-length isoform, Figs. 1a and 2) is necessary for it to interact with RACK1; since this region has substantial homology to the corresponding region of HABP1 (Fig. 3) it is a reasonable hypot

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