Biology subjects

Park, Y. S.

Publications and source records attributed to Park, Y. S..

2 recordsLinked to original sources

bioRxiv2019

Dual activity of PNGM-1, a metallo-β-lactamase and tRNase Z, pinpoints the evolutionary origin of subclass B3 metallo-β-lactamases

Antibiotic resistance is a steadily increasing global problem which could lead to a fundamental upheaval in clinical care with the potential to return us to the pre-antibiotic era1-4. The production of {beta}-lactamases, a group of enzymes that confer antibiotic resistance in Gram-negative bacteria, is now one of the major barriers in treating Gram-negative infections5. {beta}-Lactamases are classified according to their catalytic mechanisms into serine {beta}-lactamases and metallo-{beta}-lactamases6,7. There are functional and structural similarities between serine {beta}-lactamases and penicillin-binding proteins, and so serine {beta}-lactamases are thought to have evolved from a penicillin-binding protein7,8. Given the functional and structural differences between serine {beta}-lactamases and metallo-{beta}-lactamases, metallo-{beta}-lactamases are thought to have evolved from a protein other than a penicillin-binding protein, but to date this ancestor remains unknown8-11. We discovered PNGM-1, the first subclass B3 metallo-{beta}-lactamase, in deep-sea sediments that predate the antibiotic era12. Here we discover the dual activity of PNGM-1, pinpointing the evolutionary origin of subclass B3 metallo-{beta}-lactamases. Phylogenetic analysis suggested that PNGM-1 could yield insights into the evolutionary origin of subclass B3 metallo-{beta}-lactamases. We reveal the structural similarities between tRNase Zs and PNGM-1, which prompted us to investigate their evolutionary relationship and the possibility of them possessing dual enzymatic activities. We demonstrate that PNGM-1 has dual activity with both true metallo-{beta}-lactamase and tRNase Z activity, suggesting that PNGM-1 is thought to have evolved from a tRNase Z. We also show kinetic and structural comparisons between PNGM-1 and other proteins including subclass B3 metallo-{beta}-lactamases and tRNase Zs. These comparisons revealed that the B3 metallo-{beta}-lactamase activity of PNGM-1 is a promiscuous activity and subclass B3 metallo-{beta}-lactamases are thought to have evolved through PNGM-1 activity. Our work provides a foundation for the evolution of tRNase Z into subclass B3 metallo-{beta}-lactamases through the dual activity of PNGM-1.

microbiology↗

bioRxiv2019

Trajectories of change after a health-education program in Japan

BackgroundHealth education can benefit people with chronic diseases. However, in previous research those benefits were small, and reinforcement to maintain them was not effective. A possible explanation is that the benefits appeared to be small and reinforcement appeared to be ineffective because those analyses mixed data from two latent groups: one group of people who needed reinforcement and one group of people who did not. The hypothesis is that mixing the data from those two different groups caused the true effects to be \"diluted.\"\n\nMethodsTo test that hypothesis we used data from the Chronic Disease Self-Management Program in Japan, focusing on anxiety, depression, and patient-physician communication. To identify latent trajectories of change after the program, we used growth-mixture modeling. Then, to find out which baseline factors were associated with trajectory-group membership, we used logistic regression.\n\nResultsGrowth-mixture modeling revealed two trajectories - two groups that were defined by distinct patterns of change after the program. One of those patterns was improvement followed by backsliding: decay of impact. On anxiety and depression the decay of impact was large enough to be clinically important, and its prevalence was as high as 50%. Next, logistic regression analysis revealed that being in the decay-of-impact group could be predicted from multimorbidity, low self-efficacy, and high scores on anxiety or depression at baseline. In addition, one unexpected finding was an association between multimorbidity and better patient-physician communication.\n\nConclusionsThese results support the hypothesis that previous findings (i.e. apparently small effect sizes and apparently ineffective reinforcement) actually reflect \"dilution\" of large effects, which was caused by mixing of data from distinct groups. Specifically, there was one group with decay of impact and one without. Thus, evaluations of health education should include analyses of trajectory-defined groups. These results show how the group of people who are most likely to need reinforcement can be identified even before the educational program begins. Extra attention and reinforcement can then be tailored. They can be focused specifically to benefit the people with the greatest need.

epidemiology↗