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Single-nucleotide variants (SNVs) associated with Parkinson’s disease (PD) have been investigated mainly through genome-wide association studies. However, other genomic alterations, including copy number variations, remain less explored. In this study, we conducted whole-genome sequencing of primary (310 PD patients and 100 healthy individuals) and independent (100 PD patients and 100 healthy individuals) cohorts from the Korean population to identify high-resolution small genomic deletions, gains, and SNVs. Global small genomic deletions and gains were found to be associated with an increased and decreased risk of PD development, respectively. Thirty significant locus deletions were identified in PD, with most being associated with an increased PD risk in both cohorts. Small genomic deletions in clustered loci located in the GPR27 region had high enhancer signals and showed the closest association with PD. GPR27 was found to be expressed specifically in brain tissue, and GPR27 copy number loss was associated with upregulated SNCA expression and downregulated dopamine neurotransmitter pathways. Clustering of small genomic deletions on chr20 in exon 1 of the GNAS isoform was detected. In addition, we found several PD-associated SNVs, including one in the enhancer region of the TCF7L2 intron, which exhibited a cis-acting regulatory mode and an association with the beta-catenin signaling pathway. These findings provide a global, whole-genome view of PD and suggest that small genomic deletions in regulatory domains contribute to the risk of PD development.

CrrAB two-component regulatory system is associated with colistin resistance in Klebsiella pneumoniae. Recently, some K. pneumoniae isolates lacking crrAB genes have been identified. In this study, we investigated the distribution and structural variation of the crrBAC-kexD cluster. To evaluate the structural variation of the crrBAC-kexD cluster, we explored 59 clinical K. pneumoniae isolates from Korea, and 508 whole genomes of K. pneumoniae and other strains of Klebsiella sp. Significant structural variations in crrBAC-kexD and its surrounding regions were identified among K. pneumoniae genomes. Within the genus Klebsiella, the cluster was identified only in K. pneumoniae, K. variicola, and K. quasipneumoniae, which form the K. pneumoniae complex. Among the 304 available K. pneumoniae genomes, an intact crrBAC-kexD cluster was identified in 178 isolates (58.6%), while the cluster was absent in 90 isolates (29.6%). Partial deletions within the cluster were identified in 22 genomes (7.2%). The most diverse structural patterns of the crrBAC-kexD cluster were observed in ST11 strains. Some clades lacked the crrBAC-kexD cluster. The crrBAC-kexD cluster was identified in the genomes of other bacterial species, including Citrobacter freundii and Enterobacter ludwigii. The crrBAC-kexD cluster is proposed to have been acquired by the ancestor of the K. pneumoniae complex from other bacterial species and the cluster may have been lost and re-acquired repeatedly in K. pneumoniae strains according to the phylogenetic analysis. The dynamic evolution of the crrBAC-kexD cluster suggests that it may have other roles, in addition to colistin resistance, in bacterial physiology.

This study aimed to compare susceptibility map-weighted imaging (SMwI) using various MRI machines (three vendors) with N-3-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophe nyl)nortropane (We prospectively recruited 257 subjects, including 157 patients with neurodegenerative parkinsonism, 54 patients with non-neurodegenerative parkinsonism, and 46 healthy subjects from 10 hospitals between November 2019 and October 2020. All participants underwent both SMwI andThe inter-observer agreement was 0.924 and 0.942 per SN and participant, respectively. The diagnostic sensitivity of SMwI was 97.9% and 99.4% per SN and participant, respectively; its specificity was 95.9% and 95.2%, respectively, and its accuracy was 97.1% and 97.7%, respectively. There was no significant difference between the results of SMwI andThis study demonstrated that the high diagnostic performance of SMwI was maintained in a multi-centre setting with various MRI scanners, suggesting the generalisability of SMwI for determining nigrostriatal degeneration in patients with parkinsonism.• Susceptibility map-weighted imaging helps clinicians to predict nigrostriatal degeneration. • The protocol for susceptibility map-weighted imaging can be standardised across MRI vendors. • Susceptibility map-weighted imaging showed diagnostic performance comparable to that of dopamine transporter PET in a multi-centre setting with various MRI scanners.

Although deep brain stimulation (DBS) is a relatively safe and effective surgery compared with ablative surgeries, intracerebral hemorrhage (ICH) is a serious complication during DBS that could result in a fatal prognosis. We retrospectively investigated whether ICH incidence differed between patients who underwent DBS in the subthalamic nucleus (STN) and in the globus pallidus interna (GPi), together with previously identified risk factors for ICH.We retrospectively reviewed the medical records of 275 patients (527 DBS targets) who received DBS for Parkinson's disease or dystonia from April 2001 to December 2020. In cases that developed intra- or postoperative ICH, patients were classified as asymptomatic, symptomatic with temporary neurological deficit or symptomatic with permanent neurological deficit, according to patient clinical status.ICH occurred in 12 procedures (2.3%) among the 527 DBS procedures (275 patients) evaluated. In multivariable logistic regression analysis, the risk factor for all cases of ICH was systolic blood pressure (BP) during surgery (cut-off value 129.4 mmHg) (OR = 1.05, 95% CI = 1.01-1.09, P = 0.023). In addition, for ICH with permanent neurological deficit, STN target site (P = 0.024) and systolic BP during surgery (cut-off value: 148.3 mmHg) (P = 0.004) were identified as risk factors in univariable analyses.Even though the risk factor for all ICH in DBS was BP during surgery, when focused on ICH evoking permanent neurological deficit, the target location as well as systolic BP during surgery proved to be related.

The Maf polymorphic toxin system is involved in conflict between strains found in pathogenic Neisseria species such as Neisseria meningitidis and Neisseria gonorrhoeae. The genes encoding the Maf polymorphic toxin system are found in specific genomic islands called maf genomic islands (MGIs). In the MGIs, the MafB and MafI encode toxin and immunity proteins, respectively. Although the C-terminal region of MafB (MafB-CT) is specific for toxic activity, the underlying enzymatic activity that renders MafB-CT toxic is unknown in many MafB proteins due to lack of homology with domain of known function. Here we present the crystal structure of the MafB2-CTMGI-2B16B6/MafI2MGI-2B16B6 complex from N. meningitidis B16B6. MafB2-CTMGI-2B16B6 displays an RNase A fold similar to mouse RNase 1, although the sequence identity is only ~ 14.0%. MafB2-CTMGI-2B16B6 forms a 1:1 complex with MafI2MGI-2B16B6 with a Kd value of ~ 40 nM. The complementary charge interaction of MafI2MGI-2B16B6 with the substrate binding surface of MafB2-CTMGI-2B16B6 suggests that MafI2MGI-2B16B6 inhibits MafB2-CTMGI-2B16B6 by blocking access of RNA to the catalytic site. An in vitro enzymatic assay showed that MafB2-CTMGI-2B16B6 has ribonuclease activity. Mutagenesis and cell toxicity assays demonstrated that His335, His402 and His409 are important for the toxic activity of MafB2-CTMGI-2B16B6, suggesting that these residues are critical for its ribonuclease activity. These data provide structural and biochemical evidence that the origin of the toxic activity of MafB2MGI-2B16B6 is the enzymatic activity degrading ribonucleotides.

Human enteroviruses (EVs) are associated with a broad spectrum of diseases. To understand EV epidemiology, we present longitudinal data reflecting changing EV prevalence patterns in South Korea. We collected 7160 specimens from patients with suspected EV infections in ten hospitals in Gwangju, Korea during 2011–2020. RNA extraction and real-time reverse transcription polymerase chain reaction using EV-specific probes and primers were performed. EV genotyping and phylogenetic analysis were performed; EVs were detected in 3076 samples (43.0%), and the annual EV detection rate varied. EV infection rates did not differ with sex, and children aged ≤ 4 years were the most prone to EV infection; this trend did not change over time. Overall, 35 different EV types belonging to four distinctive species and rhinoviruses were identified. Although serotype distribution changed annually, the most frequently observed EVs were EV-A71 (13.1% of the cases), CVA6 (8.3%), CVB5 (7.6%), CVA16 (7.6%), CVA10 (7.5%), E18 (7.5%), E30 (7.0%), and E11 (5.0%) during 2011–2020. The predominant EV genotypes by clinical manifestation were CVB5 for aseptic meningitis; EV-A71 for hand, foot, and mouth disease cases; and CVA10 for herpangina. These results will aid the development of vaccines against EV infection and allow comprehensive disease control.

Background Brain-derived exosomes released into the blood are considered a liquid biopsy to investigate the pathophysiological state, reflecting the aberrant heterogeneous pathways of pathological progression of the brain in neurological diseases. Brain-derived blood exosomes provide promising prospects for the diagnosis of neurological diseases, with exciting possibilities for the early and sensitive diagnosis of such diseases. However, the capability of traditional exosome isolation assays to specifically isolate blood exosomes and to characterize the brain-derived blood exosomal proteins by high-throughput proteomics for clinical specimens from patients with neurological diseases cannot be assured. We report a magnetic transferrin nanoparticles (MTNs) assay, which combined transferrin and magnetic nanoparticles to isolate brain-derived blood exosomes from clinical samples. Methods The principle of the MTNs assay is a ligand-receptor interaction through transferrin on MTNs and transferrin receptor on exosomes, and electrostatic interaction via positively charged MTNs and negatively charged exosomes to isolate brain-derived blood exosomes. In addition, the MTNs assay is simple and rapid ( Results Using comparative statistical analysis, we found 21 candidate protein biomarkers that were significantly different among three groups of neurodegenerative diseases. Conclusion The MTNs assay is a convenient approach for the specific and affordable isolation of extracellular vesicles from body fluids for minimally-invasive diagnosis of neurological diseases.

With the ever-growing demand for clean and viable energy sources, the possibility and need to use a multifunctional energy system having integrated energy storage and conversion capacity has been intensified in current times. To fulfill this requirement, a search for an active material having an efficient bifunctional capacity of both hydrogen evolution reaction (HER) and supercapacitor is an essential requirement. The metal polyphosphate with the advantage of abundance, environmental friendliness, low cost, and reliable activity make it an emerging class of novel material for the present research. Herein, for the first time, the comparison of the amorphous and crystalline form of tin polyphosphate-based electrode was assessed toward hydrogen evolution reaction and supercapacitor. Considering the synergistic influence of abundant tin polyphosphate and the three-dimension structure of nickel substrate, we unswervingly deposited well-defined hierarchical in-situ amorphous SnPxOy and ex-situ crystalline SnPxOy over Ni foam using the one-step hydrothermal route. Impressively, amorphous SnPxOy/NF electrode required less over the potential of the only 100 mV with Tafel slope of 50 mV dec−1 to attain a current density of 10 mA cm−2 in comparison to crystalline SnPxOy/NF electrode showing over the potential of the only 170 mV with Tafel slope of 80 mV dec−1 to attain the same current density in 1 M KOH. Additionally, we investigated this electrode in a supercapacitor and found that amorphous SnPxOy/NF delivers a good specific capacitance of 580 F g−1 at a current density of 1 A g−1, greater rate capability, and cyclic stability. Hopefully, this study may demonstrate a promising technique for the preparation of ample, low-cost electrodes for future applications in both HER and supercapacitors applications.

The impact of different parameters on the chemical degradation of the Nafion polymer electrolyte membrane was investigated in detail under different concentrations of Fenton solution. As a consequence of chemical degradation, the performance and durability of the perfluorosulfonic acid-based electrolyte membrane in fuel cells was studied. Quantitative estimation of fluoride emitted after chemical degradation of the electrolyte membrane is done by an ex-situ fluoride emission rate-test using a potentiometric with an ion-selective electrode. The concentration of fluoride ions is easily affected by several external factors, such as total ionic strength, pH, temperature, and stirring speed, which causes many errors while reporting the fluoride concentration. Furthermore, the micromorphology of recast Nafion membranes before and after FER rest was thoroughly examined by scanning electron microscope (SEM) and X-ray photoelectric spectroscopy. Here, we report the influence of several external parameters over total fluoride concentration during the estimation of fluoride concentration for the proper correlation of the rate of chemical degradation in polymer electrolytes. This systematic study is beneficial for removing errors while measuring fluoride concentration and removing the discrepancy present in FER results reported in the literature.

Background Biotechnology in genomics, such as sequencing devices and gene quantification software, has proliferated and been applied to clinical settings. However, the lack of standards applicable to it poses practical problems in interoperability and reusability of the technology across various application domains. This study aims to visualize and identify the standard trends in clinical genomics and to suggest areas on which standardization efforts must focus. Methods Of 16,538 articles retrieved from PubMed, published from 1975 to 2020, using search keywords “genomics and standard” and “clinical genomic sequence and standard”, terms were extracted from the abstracts and titles of 15,855 articles. Our analysis includes (1) network analysis of full phases (2) period analysis with five phases; (3) statistical analysis; (4) content analysis. Results Our research trend showed an increasing trend from 2003, years marked by the completion of the human genome project (2003). The content analysis showed that keywords related to such concepts as gene types for analysis, and analysis techniques were increased in phase 3 when US-FDA first approved the next-generation sequencer. During 2017–2019, oncology-relevant terms were clustered and contributed to the increasing trend in phase 4 of the content analysis. In the statistical analysis, all the categories showed high regression values (R2 > 0.586) throughout the whole analysis period and phase-based statistical analysis showed significance only in the Genetics terminology category (P = .039*) at phase 4. Conclusions Through comprehensive trend analysis from our study, we provided the trend shifts and high-demand items in standardization for clinical genetics.

Although several studies have identified a distinct gut microbial composition in Parkinson’s disease (PD), few studies have investigated the oral microbiome or functional alteration of the microbiome in PD. We aimed to investigate the connection between the oral and gut microbiome and the functional changes in the PD-specific gut microbiome using shotgun metagenomic sequencing. The taxonomic composition of the oral and gut microbiome was significantly different between PD patients and healthy controls (P = 0.003 and 0.001, respectively). Oral Lactobacillus was more abundant in PD patients and was associated with opportunistic pathogens in the gut (FDR-adjusted P P

Epigenetic regulatory mechanisms, including DNA methylation, histone modification, chromatin remodeling, and microRNA expression, play critical roles in cell differentiation and organ development through spatial and temporal gene regulation. Neurogenesis is a sophisticated and complex process by which neural stem cells differentiate into specialized brain cell types at specific times and regions of the brain. A growing body of evidence suggests that epigenetic mechanisms, such as histone modifications, allow the fine-tuning and coordination of spatiotemporal gene expressions during neurogenesis. Aberrant histone modifications contribute to the development of neurodegenerative and neuropsychiatric diseases. Herein, recent progress in understanding histone modifications in regulating embryonic and adult neurogenesis is comprehensively reviewed. The histone modifications implicated in neurodegenerative and neuropsychiatric diseases are also covered, and future directions in this area are provided.

This study aimed to assess the trend of the maintenance status and usability of public automated external defibrillators (AEDs). Public AEDs installed in Seoul from 2013 to 2017 were included. An inspector checked the maintenance status and usability of the AEDs annually using a checklist. During the study period, 23,619 AEDs were inspected. Access to the AEDs was improved, including the absence of obstacles near the AEDs (from 90.2% in 2013 to 99.1% in 2017, p

18F-labeled fluoropropyl-carbomethoxylodopropyl-nor-s-tropane ([18F]FP-CIT) positron emission tomography (PET) is a useful tool for evaluating disease progression in Parkinson’s disease (PD) patients. We evaluated the test–retest reproducibility of [18F]FP-CIT PET measures in essential tremor (ET) and PD patients. Fifteen ET (68.9 ± 6.6 years) and 10 PD patients (70.5 ± 6.3 years; Hoehn and Yahr stage, 2.3 ± 0.8) underwent two [18F]FP-CIT PET/CT scans with an interval of 48 ± 7 day. For both the test and retest studies, standardized uptake value ratios were estimated for 90-min and 3-h acquisitions for the caudate, anterior putamen, and posterior putamen using T1-MRI-based normalization (automatic) and fixed-VOI (manual) methods, with the occipital lobe as a reference. Reproducibility was evaluated by the bias, variability, percent test–retest, within-subject coefficient of variation, repeatability coefficient, and intraclass correlation coefficient (ICC). Reproducibility was excellent, with low variability (ET: 6.99–8.02%, PD: 3.51–6.94%) and high reliability (ICC; ET: 0.88–0.96, PD: 0.98–0.99). The ET group showed higher variability and lower ICCs than the PD group. The variability in the 90-min images (ET: 7.85–8.59%, PD: 1.52–2.75%) was comparable to that in the 3-h images (ET: 6.99–8.02%, PD: 3.51–6.94%). There were no differences in variability among the subregions in the ET group. In the PD group, the variability was high in the posterior putamen (automatic method: 6.94%, manual method: 11.80%). The test–retest variability and ICCs were similar for the manual and automatic methods. [18F]FP-CIT PET is reproducible for the quantitative measurement of DAT binding in both ET and PD individuals, independent of the acquisition time or analysis method. Also, the automatic method is more suitable for evaluating early loss of DAT binding in patients with PD