Nontraditional Roles of Magnesium Ions in Modulating Sav2152: Insight from a Haloacid Dehalogenase-like Superfamily Phosphatase from Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infection has rapidly spread through various routes. A genomic analysis of clinical MRSA samples revealed an unknown protein, Sav2152, predicted to be a haloacid dehalogenase (HAD)-like hydrolase, making it a potential candidate for a novel drug target. In this study, we determined the crystal structure of Sav2152, which consists of a C2-type cap domain and a core domain. The core domain contains four motifs involved in phosphatase activity that depend on the presence of Mg2+ ions. Specifically, residues D10, D12, and D233, which closely correspond to key residues in structurally homolog proteins, are responsible for binding to the metal ion and are known to play critical roles in phosphatase activity. Our findings indicate that the Mg2+ ion known to stabilize local regions surrounding it, however, paradoxically, destabilizes the local region. Through mutant screening, we identified D10 and D12 as crucial residues for metal binding and maintaining structural stability via various uncharacterized intra-protein interactions, respectively. Substituting D10 with Ala effectively prevents the interaction with Mg2+ ions. The mutation of D12 disrupts important structural associations mediated by D12, leading to a decrease in the stability of Sav2152 and an enhancement in binding affinity to Mg2+ ions. Additionally, our study revealed that D237 can replace D12 and retain phosphatase activity. In summary, our work uncovers the novel role of metal ions in HAD-like phosphatase activity.

The effect of decontamination using quaternary ammonium chloride on the bacterial burden of hospital privacy curtains.

This quasi-experimental study aimed to identify the effect of decontamination using quaternary ammonium chloride (QAC) on bacterial burden on hospital privacy curtains. The objects were the high-touch edges of 66 polyester curtains in inpatient wards. The decontamination was performed daily (n = 22), twice-weekly (n = 22), or not performed (n = 22) for 28 days. The bacterial burden on the curtains was measured based on the number of bacteria, the proportion of curtains with >2.5 colony-forming unit/cm2 , and the proportion of curtains with multidrug-resistant organisms (MDROs). As a result, the daily or twice-weekly decontamination groups showed a significantly lower increase in bacterial burden than the no-decontamination group overall and at all four posttest times. On day 28, daily decontamination showed a lower increase in the number of bacteria (p < 0.001) and proportions of curtains with >2.5 colony form units/cm2 (p < 0.001) than the no-decontamination condition, and in the number of curtains with MDROs than twice-weekly decontamination. In conclusion, decontamination of curtains using QAC helps reduce bacterial burden, and daily decontamination is recommended up to 28 days after installation.

COVID-19 Cases and Deaths among Healthcare Personnel with the Progression of the Pandemic in Korea from March 2020 to February 2022.

Healthcare personnel (HCP) are vulnerable to COVID-19 infection due to their higher risk of contact with infected persons. The numbers of cases and deaths among HCP in Korea were divided into four periods associated with different major variants of SARS-CoV-2: GH clade, Alpha, Delta, and Omicron. To evaluate the implication of HCP infection in Korea, we overviewed the pandemic status in Korea and in other countries: the cases, deaths, excess mortality, and vaccination rates in Germany, Israel, Italy, Japan, the United Kingdom, and the United States. In about two years, there were 10,670 HCP cases among all COVID-19 cases (1.15% of 925,975 cases). HCP cases had a lower death rate (%) compared to that for all cases (0.14 versus 0.75). Nurses were the most infected (55.3%), followed by HCP of other categories (28.8%) and doctors (15.9%), while deaths were mostly reported among doctors (9 out of 15, 60%). Cases among HCP gradually increased, but the death rate decreased as the pandemic progressed. Compared to five of the other countries examined, Korea had a higher incidence of cases but a lower mortality, lower excess mortality, and a higher vaccination rate.

Effect of socioeconomic disparities on the risk of COVID-19 in 8 metropolitan cities in the Korea: a community-based study.

OBJECTIVES: Socioeconomic disparities have been reported as major risk factors contributing to the spread of coronavirus disease 2019 (COVID-19) at the community level. We conducted an epidemiological study on COVID-19 incidence risk using area-based deprivation indices (DIs) reflecting the characteristics of the susceptible population. METHODS: A database of the confirmed COVID-19 cases in 8 metropolitan cities in Korea from January 20, 2020 to December 31, 2021 was combined with area-based DI scores and standardized prevalence rates of diabetes and hypertension from the Korean Community Health Survey. Relative risk (RR) levels were estimated using a generalized linear model with a Poisson distribution by age group. RESULTS: The risk of COVID-19 incidence generally increased with increasing age, especially in patients aged ≥75 years. The RR of COVID-19 incidence per interquartile range increment of the composite deprivation index (composite DI) was 1.54 (95% confidence interval [CI], 1.34 to 1.70). Notably, in the first wave, the risk of COVID-19 incidence was approximately 3 times higher in the region with the lowest socioeconomic status than in the region with the highest status (RR, 3.08; 95% CI, 2.42 to 3.78 based on the the composite DI and RR, 3.13; 95% CI, 2.53 to 3.83 based on the social deprivation index). CONCLUSIONS: This study provides scientific evidence that socioeconomic deprivation is an important risk factor for the spread of COVID-19. This finding suggests that a mid-term to long-term strategy is needed to protect susceptible populations and reduce the burden of COVID-19 in the community.

Structural resemblance of the DNAJA-family protein, Tid1, to the DNAJB-family Hsp40.

The specific pair of heat shock protein 70 (Hsp70) and Hsp40 constitutes an essential molecular chaperone system involved in numerous cellular processes, including the proper folding/refolding and transport of proteins. Hsp40 family members are characterized by the presence of a conserved J-domain (JD) that functions as a co-chaperone of Hsp70. Tumorous imaginal disc 1 (Tid1) is a tumor suppressor protein belonging to the DNAJA3 subfamily of Hsp40 and functions as a co-chaperone of the mitochondrial Hsp70, mortalin. In this work, we performed nuclear magnetic resonance spectroscopy to determine the solution structure of JD and its interaction with the glycine/phenylalaninerich region (GF-motif) of human Tid1. Notably, Tid1-JD, whose conformation was consistent with that of the DNAJB1 JD, appeared to stably interact with its subsequent GF-motif region. Collectively with our sequence analysis, the present results demonstrate that the functional and regulatory mode of Tid1 resembles that of the DNAJB1 subfamily members rather than DNAJA1 or DNAJA2 subfamily proteins. Therefore, it is suggested that an allosteric interaction between mortalin and Tid1 is involved in the mitochondrial Hsp70/Hsp40 chaperone system. [BMB Reports 2022; 55(10): 488-493].

Epidemiological Characteristics and Transmission Patterns of COVID-19 Cases Among Children and Adolescents Aged 0-18 Years in South Korea.

BACKGROUND: In South Korea, the epidemiological characteristics of children and adolescents infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have not been reported to date. The purpose of this study was to identify major epidemiological characteristics and transmission patterns of coronavirus disease 2019 (COVID-19) in children and adolescents. METHODS: This study was conducted through a system integrated in an epidemiological investigation by the Korea Disease Control and Prevention Agency from January 20, 2020, to June 5, 2021. We analyzed the epidemiological characteristics of 14,967 children and adolescents with COVID-19 according to the age groups and transmission age patterns of 3721 infector-infectee pairs in South Korea. RESULTS: Among the total confirmed COVID-19 cases, 14,967 patients were aged 0-18 years. The most affected age group among children and adolescents were those aged 16-18 years (3589, 24.0%). For all age groups, the infection route through friends and family members (31.9%) was the highest. For the contact age pattern analysis, infection from infectors aged 30-49 years to infectees aged 0-12 years showed a statistically significant relation (p <0.001) compared to that in other age groups. On the other hand, among the infectees aged 13-15 years and 16-18 years were significantly related with adolescents aged 10-19 years (p <0.05). CONCLUSION: These results suggest that adolescents aged 13-18 years were more infected with COVID-19 than those aged 0-12 years. Furthermore, they are particularly more likely to be infected by friends and family members. Besides, in patients aged 13-18 years, transmission of SARS-CoV-2 was more common from adolescents to adolescents than from adults to adolescents. This research will provide scientific evidence for school policies and vaccine strategies for COVID-19 prevention in children and adolescents.

A Genome-Wide Association Study of a Korean Population Identifies Genetic Susceptibility to Hypertension Based on Sex-Specific Differences.

Genome-wide association studies have expanded our understanding of the genetic variation of hypertension. Hypertension and blood pressure are influenced by sex-specific differences; therefore, genetic variants may have sex-specific effects on phenotype. To identify the genetic factors influencing the sex-specific differences concerning hypertension, we conducted a heterogeneity analysis of a genome-wide association study (GWAS) on 13,926 samples from a Korean population. Using the Illumina exome chip data of the population, we performed GWASs of the male and female population independently and applied a statistical test that identified heterogeneous effects of the variants between the two groups. To gain information about the biological implication of the genetic heterogeneity, we used gene set enrichment analysis with GWAS catalog and pathway gene sets. The heterogeneity analysis revealed that the rs11066015 of ACAD10 was a significant locus that had sex-specific genetic effects on the development of hypertension. The rs2074356 of HECTD4 also showed significant genetic heterogeneity in systolic blood pressure. The enrichment analysis showed significant results that are consistent with the pathophysiology of hypertension. These results indicate a sex-specific genetic susceptibility to hypertension that should be considered in future genetic studies of hypertension.

Structural Interplays in the Flexible N-Terminus and Scaffolding Domain of Human Membrane Protein Caveolin 3.

Caveolins are critical for the formation of caveolae, which are small invaginations of the plasma membrane involved in a variety of biological processes. Caveolin 3 (Cav3), one of three caveolin isoforms, is an integral membrane protein mainly expressed in muscle tissues. Although various human diseases associated with Cav3 have been reported, structural characterization of Cav3 in the membrane has not been investigated in enough depth to understand the structure-function relationship. Here, using solution NMR, we characterized membrane association, structural communications, and molecular dynamics of the monomeric Cav3 in detergent micelle environment, particularly focused on the whole N-terminal part that is composed of the flexible N-terminus and the scaffolding domain. The results revealed a complicated structural interplay of the individual segments composing the whole N-terminal part, including the pH-dependent helical region, signature motif-like region, signature motif, and scaffolding domain. Collectively, the present study provides novel structural insights into the whole N-terminal part of Cav3 that plays important biological roles in cellular processes and diseases. In particular, given that several disease-related mutations are located at the whole N-terminal part of Cav3, the sophisticated communications in the whole N-terminal segments are likely to have relevance to the molecular basis of Cav3-related disease.

Comparative Co-Evolution Analysis Between the HA and NA Genes of Influenza A Virus.

Influenza A virus subtypes are determined based on envelope proteins encoded by the hemagglutinin (HA) gene and the neuraminidase (NA) gene, which are involved in attachment to the host, pathogenicity, and progeny production. Here, we evaluated such differences through co-evolution analysis between the HA and NA genes based on subtype and host. Event-based cophylogeny analysis revealed that humans had higher cospeciation values than avian. In particular, the yearly ML phylogenetic trees for the H1N1 and H3N2 subtypes in humans displayed similar topologies between the two genes in humans. Substitution analysis was verifying the strong positive correlation between the two genes in the H1N1 and H3N2 subtypes in humans compared with those in avian and swine. These results provided a proof of principle for the further development of vaccines according to hosts and subtypes against Influenza A virus.

Correlations Between the Incidence of National Notifiable Infectious Diseases and Public Open Data, Including Meteorological Factors and Medical Facility Resources.

OBJECTIVES: This study was performed to investigate the relationship between the incidence of national notifiable infectious diseases (NNIDs) and meteorological factors, air pollution levels, and hospital resources in Korea. METHODS: We collected and stored 660,000 pieces of publicly available data associated with infectious diseases from public data portals and the Diseases Web Statistics System of Korea. We analyzed correlations between the monthly incidence of these diseases and monthly average temperatures and monthly average relative humidity, as well as vaccination rates, number of hospitals, and number of hospital beds by district in Seoul. RESULTS: Of the 34 NNIDs, malaria showed the most significant correlation with temperature (r=0.949, p<0.01) and concentration of nitrogen dioxide (r=-0.884, p<0.01). We also found a strong correlation between the incidence of NNIDs and the number of hospital beds in 25 districts in Seoul (r=0.606, p<0.01). In particular, Geumcheon-gu was found to have the lowest incidence rate of NNIDs and the highest number of hospital beds per patient. CONCLUSIONS: In this study, we conducted a correlational analysis of public data from Korean government portals that can be used as parameters to forecast the spread of outbreaks.

A Visualization Tool for Calculating the Genetic Substitution Patterns Between Two Different Groups.

We developed simulation tool for influenza virus variation (SimFluVar), an analytics software for calculating genomic variation among members of the influenza virus group. This study is related to computational evolutionary biology and evolutionary bioinformatics. SimFluVar is an analytical tool that can be used to calculate codon substitution patterns of viral genes. Designed to compare a large number of nucleotide sequences, SimFluVar provides precise patterns of codon variations between two viral groups, especially for the influenza virus. SimFluVar also provides useful functions, such as editing and visualization of the result matrix. This new tool can be used to analyze codon variation patterns over time as well as to analyze the genomic differences between viruses obtained from different geographical locations. SimFluVar is developed in C++, and Java RCP is used as a distribution package. SimFluVar, including the associated documentation, manuals, and examples, is publicly available at http://lcbb.snu.ac.kr/simfluvar.

Effects of methamphetamine on single unit activity in rat medial prefrontal cortex in vivo.

To investigate how neuronal activity in the prefrontal cortex changes in an animal model of schizophrenia, we recorded single unit activity in the medial prefrontal cortex of urethane-anesthetized and awake rats following methamphetamine (MA) administration. Systemic MA injection (4 mg/kg, IP) induced inconsistent changes, that is, both enhancement and reduction, in unit discharge rate, with a subset of neurons transiently (<30 min) elevating their activities. The direction of firing rate change was poorly predicted by the mean firing rate or the degree of burst firing during the baseline period. Also, simultaneously recorded units showed opposite directions of firing rate change, indicating that recording location is a poor predictor of the direction of firing rate change. These results raise the possibility that systemic MA injection induces random bidirectional changes in prefrontal cortical unit activity, which may underlie some of MA-induced psychotic symptoms.