Structure of MSPL–inhibitor complex

Infection of certain influenza viruses is triggered when its HA is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, whereas the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R↓ sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal α-helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interacts with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19

ヘキチ イリョウ キョテン ビョウイン ニオケル センモン ガイライ ノ カンジャ ジュリョウ ドウコウ ニ オヨボス エイキョウ

There were few reports about the role of medical specialists in community medicine organizations such as hospitals in rural area where the number of doctors is insufficient. The aim of this study was to investigate the effect of a medical specialist for collagen vascular diseases having started periodically ambulatory care in the medical institution of the area where the specialist was absent. We examined the trend of outpatients with a collagen vascular disease about moving the hospital comparing before and after the specialist started to work in the medical institution. The number of outpatients with a collagen vascular disease in the medical institution became 95 at 3 years and a half after the specialist started to work there. There were many transfer patients from medical institutions other than the area, and the distance from their home to the hospital was shortened by changing the hospital in most of patients. The ambulatory care performed periodically and continuously by the specialist in a community medicine organization showed significances that patients became to receive the special medical care by the specialist

Distribution of corneal spherical aberration in a Tanzanian population.

PurposeTo investigate the distribution of corneal spherical aberration (SA) in Tanzanian people of African descent, and to examine the correlation between corneal SA and ocular parameters.DesignCross-sectional population-based study.MethodsResidents aged 40 years and older in three villages in the Mkuranga district in Tanzania were enlisted as study participants. Corneal higher-order aberrations (HOAs) for the right eye were measured with a wavefront analyzer (KR-1W, Topcon) and calculated for the central 6.0-mm zone. Corneal curvature radius (CR), corneal astigmatism, and axial length (AL) were also measured and their correlation with corneal SA was assessed.ResultsThe right eyes of 657 participants (336 male, 321 female) were analyzed. The mean age of the subjects was 57.2 ± 10.3 years (mean ± SD). The mean corneal SA (Zernike spherical aberration coefficient C40) was 0.188 ± 0.095 μm (-0.242 to 0.613). The SAs in about three-quarters of all subjects were between 0.10 and 0.30 μm. The root mean squares of total corneal HOAs and the third- and fourth-order aberrations were 0.629 ± 0.250 μm, 0.539 ± 0.236 μm, and 0.269 ± 0.110 μm, respectively. Corneal SA showed weak significant correlations with CR (Spearman's rank correlation coefficient, r = -0.177, p ConclusionsThis finding may be beneficial for selecting aspheric intraocular lens in this population

Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza

Infection of certain influenza viruses is triggered when its HA is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, whereas the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R↓ sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal α-helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interacts with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19