Xu, p. | bioRxiv Science

bioRxiv2021

Structural basis for recognition of anti-migraine drug lasmiditan by the serotonin receptor 5-HT1F-G protein complex

Migraine headache has become global pandemics and is the number one reason of work day loss. The most common drugs for anti-migraine are the triptan class of drugs that are agonists for serotonin receptors 5-HT1B and 5-HT1D. However, these drugs have side effects related to vasoconstriction that could have fatal consequences of ischemic heart disease and myocardial infarction. Lasmiditan is a new generation of anti-migraine drug that selectively binds to the serotonin receptor 5-HT1F due to its advantage over the tripan class of anti-migraine drugs. Here we report the cryo-EM structure of the 5-HT1F in complex with Lasmiditan and the inhibitory G protein heterotrimer. The structure reveals the mechanism of 5-HT1F-selective activation by Lasmiditan and provides a template for rational design of anti-migraine drugs.

biophysics↗

bioRxiv2019

Diagnostic value of galactomannan in bronchoalveolar lavage fluid for chronic respiratory disease with pulmonary aspergillosis

ObjectiveTo explore the diagnostic value of the bronchoalveolar lavage fluid galactomannan (BALF GM) test for chronic respiratory disease with pulmonary aspergillosis, and establish the optimal cut-off value.\n\nMethodsA total of 180 chronic respiratory disease patients seen at the Respiratory Medicine Department of Peking University Shenzhen Hospital from September 2017 to September 2018 were analyzed. According to the diagnostic criteria, we divided the patients into the case group (n = 70, comprising 5, 20, and 45 proven, probable, and possible cases, respectively) and the control group (n = 110). Bronchoalveolar lavage fluid was collected, and the BALF GM test results were analyzed.\n\nResultsA non-parametric rank-sum test showed that the mean rank of the case group was 140.80, which was higher than that of the control group (58.49). The Z-value was 10.335 (P = 0.000), indicating that the general distribution of BALF GM differed between the two groups. A BALF GM cut-off value of 0.485 showed the highest diagnostic efficacy for pulmonary aspergillosis. The sensitivity, specificity, positive predictive value, and negative predictive value were 92.9%, 100%, 92.8%, and 100%, respectively. As the cut-off value increased, the specificity and sensitivity of the BALF GM test increased and decreased, respectively.\n\nConclusionsThe BALF GM test can be used confirm the diagnosis of patients with pulmonary aspergillosis and chronic respiratory disease. The optimum BALF GM cut-off value was 0.485. Antifungal therapy is important for treating pulmonary aspergillus infection in patients with chronic respiratory disease.

microbiology↗