Prion-like protein aggregates exploit the RHO GTPase to cofilin-1 signaling pathway to enter cells
Protein aggregation is a hallmark of diverse neurodegenerative diseases. Multiple lines of evidence have revealed that protein aggregates can penetrate inside cells and spread like prions. How such aggregates enter cells remains elusive. Through a focused siRNA screen targeting genes involved in membrane trafficking, we discovered that mutant SOD1 aggregates, like viruses, exploit cofilin-1 to remodel cortical actin and enter cells. Upstream of cofilin-1, signalling from the RHO GTPase and the ROCK1 and LIMK1 kinases controls cofilin-1 activity to remodel actin and modulate aggregate entry. In the spinal cord of symptomatic SOD1G93A transgenic mice, cofilin-1 phosphorylation is increased and actin dynamics altered. Importantly, the RHO to cofilin-1 signalling pathway also modulates entry of tau and α-synuclein aggregates. Our results identify a common host cell signalling pathway that diverse protein aggregates exploit to remodel actin and enter cells.
Peng Li, Rongmei Wang, Hongchao Jiao, Xiaojuan Wang, Jingpeng Zhao, Hai Lin
Chun-Chieh Huang, Raghuvaran Narayanan, Noah Warshawsky, Sriram Ravindran
Org. Biomol. Chem., 2018, Accepted Manuscript DOI: 10.1039/C8OB00979A, CommunicationShuhei Kusano, Sae Konishi, Yuji Yamada, Osamu Hayashida Three series of water-soluble anthracene-appended benzoxaboroles 1a-c were developed; their binding affinity toward cis-1,2-diols was explored by conventional fluorescence titrations to demonstrate the role of benzoxaborole as a general recognition... The content of this RSS Feed (c) The Royal Society of Chemistry
Org. Biomol. Chem., 2018, Advance Article DOI: 10.1039/C8OB01015C, CommunicationClaire L. Jarvis, Neyra M. Jemal, Spencer Knapp, Daniel Seidel A new preparation of [small delta]-lactams is reported. To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry
Org. Biomol. Chem., 2018, Advance Article DOI: 10.1039/C8OB00942B, PaperXiangqing Chang, Xiongfei Zhang, Zhiwei Chen The atom-economical characteristics, mild conditions, simple operation and broad substrate scope demonstrated the synthetic value of this protocol. To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry
DISCUSSION: Current WHO guidelines support the use of fluoroquinolones (first-line), β-lactams (second-line) and cephalosporins (second-line) which accords with currently available evidence and other international guidelines, and there is no strong evidence for changing this guidance. Azithromycin is appropriate as a second-line therapy in regions where the rate of non-susceptibility of ciprofloxacin is known to be high, and research suggests that, from a cardiac point of view, azithromycin is safer than other macrolide antibiotics. Cefixime is also a reasonable alternative, although its use must be weighed against th...
Conclusion Further pragmatic trials are required to optimise management of hospitalised children with severe and very severe pneumonia. PMID: 29790844 [PubMed - in process]
Authors: Ashorn P PMID: 29790843 [PubMed - in process]
Conclusions Current WHO guidelines supporting the use of gentamicin and penicillin for hospital-based patients or gentamicin (IM) and amoxicillin (oral) when referral to a hospital is not possible are in accordance with currently available evidence and other international guidelines, and there is no strong evidence to change this. The benefit of a cephalosporin alone or in combination as a second-line therapy in regions with known high rates of non-susceptibility is not well established. Further research into hospital-acquired sepsis in neonates and children is required. PMID: 29790842 [PubMed - in process]
Conclusions In view of the changing non-susceptibility rates worldwide, empirical therapy for cholera infection in paediatric patients should be changed to single-dose azithromycin (20 mg/kg), a safe and effective medication with ease of administration. Erythromycin (12.5 mg/kg four times daily for 3 days) exhibits similar bacteriological and clinical success and should be listed as a second-line therapy. Fluid resuscitation remains the cornerstone of management of paediatric cholera infection, and prevention of infection by promoting access to clean water and sanitation is paramount. PMID: 29790841 [PubMed - in process]