Photolysis of a caged peptide reveals rapid action of NSF prior to neurotransmitter release

Author Posting. © The Author(s), 2007. This is the author's version of the work. It is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 105 (2008): 347-352, doi:10.1073/pnas.0707197105.The time at which the N-ethylmaleimide-sensitive factor (NSF) acts during synaptic vesicle trafficking was identified by time-controlled perturbation of NSF function with a photo-activatable inhibitory peptide. Photolysis of this caged peptide in the squid giant presynaptic terminal caused an abrupt (0.2 s) slowing of the kinetics of the postsynaptic current (PSC) and a more gradual (2-3 s) reduction in PSC amplitude. Based on the rapid rate of these inhibitory effects relative to the speed of synaptic vesicle recycling, we conclude that NSF functions in reactions that immediately precede neurotransmitter release. Our results indicate the locus of SNARE protein recycling in presynaptic terminals and reveal a new target for rapid regulation of transmitter release.T.K. was supported by a Grass Fellowship in Neuroscience, an HFSP long-term fellowship and the Feodor-Lynen Program of the Alexander von Humboldt Foundation. Y.L. received a American Heart Association predoctoral fellowship. The research also was supported by NIH NS-21624

Asthma treatment in children: A pragmatic approach

Background. Asthma is a heterogeneous condition characterised by chronic inflammation and variable expiratory airflow limitation, with airway reversibility. Management of chronic inflammation with anti-asthma medication improves asthma control and quality of life.Objectives. To provide an evidence-based approach for chronic asthma management in young children and adolescents and provide guidance on the use of new asthma drugs in children.Methods. The South African Childhood Asthma Working Group (SACAWG) convened in January 2017. The asthma treatment task group reviewed the available scientific literature and international asthma treatment guidelines. The evidence was then graded according to the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system and recommendations were made based on scientific evidence and local context. Asthma management recommendations were made for children Ë‚6 years of age and older children and adolescents, as well as for stepping up and stepping down of therapy. This review does not include biologics or novel asthma drugs, which are covered in another CME article in this edition of SAMJ.Conclusions. To ensure good response, treatment and adherence, type of medication, device and checking of technique are all critical. Stepping up of therapy should be done only after ensuring good adherence and technique. Once therapeutic response is achieved, medication administration has to be stepped down to improve ease of use and avoid unnecessary side-effects