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BACKGROUND: Glycated albumin (GA) is an indicator of glycemic variability over the past 2-4 weeks and has suitable characteristics for predicting the prognosis of ischemic stroke during the acute phase. This study evaluated the association between early neurological deterioration (END) and GA values in patients with acute ischemic stroke (AIS). METHODS: We assessed consecutive patients with AIS between 2022 and 2023 at two large medical centers in Korea. END was defined as an increase of ≥ 2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. We evaluated various glycemic parameters including fasting glucose (mg/dL), hemoglobin A1c (%), and GA (%). RESULTS: In total, 531 patients with AIS were evaluated (median age: 69 years, male sex: 66.3%). In the multivariable logistic regression analysis, GA value was positively associated with END (adjusted odds ratio [aOR] = 3.24, 95% confidence interval [CI]: 1.10-9.50). Initial NIHSS score (aOR = 1.04, 95% CI: 1.01-1.08) and thrombolytic therapy (aOR = 2.06, 95% CI: 1.14-3.73) were also associated with END. In a comparison of the predictive power of glycemic parameters for END, GA showed a higher area under the curve value on the receiver operating characteristic curve than fasting glucose and hemoglobin A1c. CONCLUSIONS: High GA values were associated with END in patients with AIS. Furthermore, GA was a better predictor of END than fasting glucose or hemoglobin A1c.
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Albúmina Sérica Glicada , Productos Finales de Glicación Avanzada , Accidente Cerebrovascular Isquémico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Glucemia/metabolismo , Glucemia/análisis , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/diagnóstico , PronósticoRESUMEN
OBJECTIVE: Drug incompatibility, a significant subset of medication errors, threaten patient safety during the medication administration phase. Despite the undeniably high prevalence of drug incompatibility, it is currently poorly understood because previous studies are focused predominantly on intensive care unit (ICU) settings. To enhance patient safety, it is crucial to expand our understanding of this issue from a comprehensive viewpoint. This study aims to investigate the prevalence and mechanism of drug incompatibility by analysing hospital-wide prescription and administration data. METHODS: This retrospective cross-sectional study, conducted at a tertiary academic hospital, included data extracted from the clinical data warehouse of the study institution on patients admitted between January 1, 2021, and May 31, 2021. Potential contacts in drug pairs (PCs) were identified using the study site clinical workflow. Drug incompatibility for each PC was determined by using a commercial drug incompatibility database, the Trissel's™ 2 Clinical Pharmaceutics Database (Trissel's 2 database). Drivers of drug incompatibility were identified, based on a descriptive analysis, after which, multivariate logistic regression was conducted to assess the risk factors for experiencing one or more drug incompatibilities during admission. RESULTS: Among 30,359 patients (representing 40,061 hospitalisations), 24,270 patients (32,912 hospitalisations) with 764,501 drug prescriptions (1,001,685 IV administrations) were analysed, after checking for eligibility. Based on the rule for determining PCs, 5,813,794 cases of PCs were identified. Among these, 25,108 (0.4 %) cases were incompatible PCs: 391 (1.6 %) PCs occurred during the prescription process and 24,717 (98.4 %) PCs during the administration process. By classifying these results, we identified the following drivers contributing to drug incompatibility: incorrect order factor; incorrect administration factor; and lack of related research. In multivariate analysis, the risk of encountering incompatible PCs was higher for patients who were male, older, with longer lengths of stay, with higher comorbidity, and admitted to medical ICUs. CONCLUSIONS: We comprehensively described the current state of drug incompatibility by analysing hospital-wide drug prescription and administration data. The results showed that drug incompatibility frequently occurs in clinical settings.
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AIMS: Assessing the risk for HF rehospitalization is important for managing and treating patients with HF. To address this need, various risk prediction models have been developed. However, none of them used deep learning methods with real-world data. This study aimed to develop a deep learning-based prediction model for HF rehospitalization within 30, 90, and 365 days after acute HF (AHF) discharge. METHODS AND RESULTS: We analysed the data of patients admitted due to AHF between January 2014 and January 2019 in a tertiary hospital. In performing deep learning-based predictive algorithms for HF rehospitalization, we use hyperbolic tangent activation layers followed by recurrent layers with gated recurrent units. To assess the readmission prediction, we used the AUC, precision, recall, specificity, and F1 measure. We applied the Shapley value to identify which features contributed to HF readmission. Twenty-two prognostic features exhibiting statistically significant associations with HF rehospitalization were identified, consisting of 6 time-independent and 16 time-dependent features. The AUC value shows moderate discrimination for predicting readmission within 30, 90, and 365 days of follow-up (FU) (AUC:0.63, 0.74, and 0.76, respectively). The features during the FU have a relatively higher contribution to HF rehospitalization than features from other time points. CONCLUSIONS: Our deep learning-based model using real-world data could provide valid predictions of HF rehospitalization in 1 year follow-up. It can be easily utilized to guide appropriate interventions or care strategies for patients with HF. The closed monitoring and blood test in daily clinics are important for assessing the risk of HF rehospitalization.
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The effects of ultraviolet (UV) radiation on brain function have previously been investigated; however, the specific neurotransmitter-mediated mechanisms responsible for UV radiation-induced neurobehavioral changes remain elusive. In this study, we aimed to explore the mechanisms underlying UV radiation-induced neurobehavioral changes. In a mouse model, we observed that UV irradiation of the skin induces deficits in hippocampal memory, synaptic plasticity, and adult neurogenesis, as well as increased dopamine levels in the skin, adrenal glands, and brain. Chronic UV exposure altered the expression of genes involved in dopaminergic neuron differentiation. Furthermore, chronic peripheral dopamine treatments resulted in memory deficits. Systemic administration of a dopamine D1/D5 receptor antagonist reversed changes in memory, synaptic plasticity, adult neurogenesis, and gene expression in UV-irradiated mice. Our findings provide converging evidence that chronic UV exposure alters dopamine levels in the central nervous system and peripheral organs, including the skin, which may underlie the observed neurobehavioral shifts, such as hippocampal memory deficits and impaired neurogenesis. This study underscores the importance of protection from UV exposure and introduces the potential of pharmacological approaches targeting dopamine receptors to counteract the adverse neurological impacts of UV exposure.
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Dopamina , Trastornos de la Memoria , Rayos Ultravioleta , Animales , Dopamina/metabolismo , Rayos Ultravioleta/efectos adversos , Trastornos de la Memoria/etiología , Trastornos de la Memoria/metabolismo , Ratones , Masculino , Neurogénesis/efectos de la radiación , Plasticidad Neuronal/efectos de la radiación , Hipocampo/metabolismo , Hipocampo/efectos de la radiación , Piel/metabolismo , Piel/efectos de la radiación , Transducción de Señal , Ratones Endogámicos C57BL , Receptores de Dopamina D1/metabolismo , Encéfalo/metabolismo , Encéfalo/efectos de la radiación , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/efectos de la radiaciónRESUMEN
Objective: Recently, evidence has suggested that the pathophysiology and risk factors of intracranial atherosclerosis (ICAS) differs from those of extracranial atherosclerosis (ECAS). In addition, novel parameters reflecting metabolic conditions, such as insulin resistance or atherogenic dyslipidemia, based on triglycerides (TG) and other biomarkers, have emerged. In this study, we evaluated the association between TG-related parameters and symptomatic cerebral atherosclerosis in patients with acute ischemic stroke resulting from large artery atherosclerosis (LAA). Methods: We assessed consecutive acute LAA-stroke patients between January 2010 and December 2020. Based on the radiological findings, we classified the relevant symptomatic arteries that caused the index stroke into LAA-ICAS and LAA-ECAS. As TG-related parameters, the atherogenic index of plasma (AIP) and TG-glucose (TyG) index were calculated according to the following formulas: AIP = log10 (TG Level/High-density Lipoprotein Cholesterol Level), TyG Index = Ln (TG Level × Glucose Level/2). Results: A total of 519 patients with LAA-stroke were evaluated. In multivariable logistic regression analysis to identify predictors of LAA-ICAS, AIP was significantly associated with LAA-ICAS (adjusted odds ratio [aOR], 3.60; 95% confidence interval [CI], 1.60-8.06). TyG index also showed a statistically significant relationship with LAA-ICAS (aOR, 1.60; 95% CI, 1.11-2.32). However, TG per se did not show a statistical association with LAA-ECAS. Conclusion: TG-related parameters were more closely associated with stroke by ICAS than by ECAS. The metabolic conditions reflected by the AIP or TyG index, rather than hypertriglyceridemia itself, may play a greater role in determining the relevant vessel causally involved in a stroke.
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BACKGROUND: We determined whether the severity of sleep apnea increases the risk of mortality in patients with multiple system atrophy (MSA) with and without stridor. MethodsThis retrospective study included patients who underwent polysomnography within one year after diagnosis of probable MSA. Stridor, sleep apnea, and arousal from sleep were determined using full-night polysomnography. Disease severity was measured using the Unified MSA Rating Scale (UMSARS). Survival data were collected and analyzed using Cox regression analysis. RESULTS: Sixty-four patients with MSA were included. During a median follow-up of 34.5 months, 49 (76.6 %) patients died. Stridor was present in 56.3 % of patients. Patients with stridor had more severe sleep apnea and shorter sleep time than those without, but the hazard ratio (HR) for death did not differ between patients with and without stridor. Among patients without stridor, apnea-hypopnea index ≥30/h (HR, 6.850; 95 % confidence interval [CI], 1.983-23.664; p = 0.002) and a score of UMSARS I + II (HR, 1.080; 95 % CI, 1.040-1.121; p < 0.001) were independently associated with death. In contrast, among patients with stridor, frequent arousals from sleep (HR, 0.254; 95 % CI, 0.089-0.729; p = 0.011) were a significant factor associated with longer survival, while MSA-cerebellar type tended to be associated with poor survival (HR, 2.195; 95 % CI, 0.941-5.120; p = 0.069). CONCLUSION: The severity of sleep apnea might be a significant predictor of shorter survival in MSA patients without stridor, whereas frequent arousals from sleep might be a significant predictor for longer survival in MSA patients with stridor.
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Atrofia de Múltiples Sistemas , Polisomnografía , Índice de Severidad de la Enfermedad , Síndromes de la Apnea del Sueño , Humanos , Atrofia de Múltiples Sistemas/mortalidad , Atrofia de Múltiples Sistemas/complicaciones , Atrofia de Múltiples Sistemas/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Síndromes de la Apnea del Sueño/mortalidad , Síndromes de la Apnea del Sueño/complicaciones , Pronóstico , Ruidos Respiratorios/etiología , Ruidos Respiratorios/fisiopatología , Estudios de SeguimientoRESUMEN
BACKGROUND: Insects encounter various environmental stresses, in response to which they generate reactive oxygen species (ROS). Superoxide dismutase (SOD) is an antioxidant metalloenzyme that scavenges superoxide radicals to prevent oxidative damage. OBJECTIVE: To investigate expressions of SODs under oxidative stress in Tenebrio molitor. METHODS: Here, we investigated the transcriptional expression of SODs by pesticide and heavy metals in Tenebrio moltior. First, we searched an RNA-Seq database for T. molitor SOD (TmSOD) genes and identified two SOD isoforms (TmSOD1-iso1 and iso2). We examined their activities under developmental stage, tissue-specific, and various types (pesticide and heavy metal) of oxidative stress by using qPCR. RESULTS: Our results revealed two novel forms of TmSODs. These TmSODs had a copper/zinc superoxide dismutase domain, active site, Cu2+ binding site, Zn2+ binding site, E-class dimer interface, and P-class dimer interface. TmSODs (TmSOD1-iso1 and iso2) were expressed in diverse developmental phases and tissues. Pesticides and heavy metals caused an upregulation of these TmSODs. CONCLUSION: Our findings suggest that the two TmSODs have different functions in T. molitor, providing insights into the detoxification ability of T. molitor.
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Estrés Oxidativo , Superóxido Dismutasa , Tenebrio , Animales , Tenebrio/genética , Tenebrio/enzimología , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Proteínas de Insectos/química , Metales Pesados/metabolismo , Simulación por Computador , Plaguicidas/metabolismoRESUMEN
BACKGROUND: The Bradybaenidae snail Karaftohelix adamsi is endemic to Korea, with the species tracked from Island Ulleung in North Gyeongsang Province of South Korea. K. adamsi has been classified under the Endangered Wildlife Class II species of Korea and poses a severe risk of extinction following habitat disturbances. With no available information at the DNA (genome) or mRNA (transcriptome) level for the species, conservation by utilizing informed molecular resources seems difficult. OBJECTIVE: In this study, we used the Illumina short-read sequencing and Trinity de novo assembly to draft the reference transcriptome of K. adamsi. RESULTS: After assembly, 13,753 unigenes were obtained of which 10,511 were annotated to public databases (a maximum of 10,165 unigenes found homologs in PANM DB). A total of 6,351, 3,535, 358, and 3,407 unigenes were ascribed to the functional categories under KOG, GO, KEGG, and IPS, respectively. The transcripts such as the HSP 70, aquaporin, TLR, and MAPK, among others, were screened as putative functional resources for adaptation. DNA transposons were found to be thickly populated in comparison to retrotransposons in the assembled unigenes. Further, 2,164 SSRs were screened with the promiscuous presence of dinucleotide repeats such as AC/GT and AG/CT. CONCLUSION: The transcriptome-guided discovery of molecular resources in K. adamsi will not only serve as a basis for functional genomics studies but also provide sustainable tools to be utilized for the protection of the species in the wild. Moreover, the development of polymorphic SSRs is valuable for the identification of species from newer habitats and cross-species genotyping.
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Especies en Peligro de Extinción , Repeticiones de Microsatélite , Caracoles , Transcriptoma , Animales , Repeticiones de Microsatélite/genética , Caracoles/genética , Transcriptoma/genética , República de Corea , Anotación de Secuencia Molecular , Aptitud GenéticaRESUMEN
Posttranslational modifications regulate the properties and abundance of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that mediate fast excitatory synaptic transmission and synaptic plasticity in the central nervous system. During long-term depression (LTD), protein tyrosine phosphatases (PTPs) dephosphorylate tyrosine residues in the C-terminal tail of AMPA receptor GluA2 subunit, which is essential for GluA2 endocytosis and group I metabotropic glutamate receptor (mGluR)-dependent LTD. However, as a selective downstream effector of mGluRs, the mGluR-dependent PTP responsible for GluA2 tyrosine dephosphorylation remains elusive at Schaffer collateral (SC)-CA1 synapses. In the present study, we find that mGluR5 stimulation activates Src homology 2 (SH2) domain-containing phosphatase 2 (SHP2) by increasing phospho-Y542 levels in SHP2. Under steady-state conditions, SHP2 plays a protective role in stabilizing phospho-Y869 of GluA2 by directly interacting with GluA2 phosphorylated at Y869, without affecting GluA2 phospho-Y876 levels. Upon mGluR5 stimulation, SHP2 dephosphorylates GluA2 at Y869 and Y876, resulting in GluA2 endocytosis and mGluR-LTD. Our results establish SHP2 as a downstream effector of mGluR5 and indicate a dual action of SHP2 in regulating GluA2 tyrosine phosphorylation and function. Given the implications of mGluR5 and SHP2 in synaptic pathophysiology, we propose SHP2 as a promising therapeutic target for neurodevelopmental and autism spectrum disorders.
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Endocitosis , Depresión Sináptica a Largo Plazo , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Receptores AMPA , Receptores de Glutamato Metabotrópico , Receptores AMPA/metabolismo , Animales , Fosforilación , Endocitosis/fisiología , Depresión Sináptica a Largo Plazo/fisiología , Receptores de Glutamato Metabotrópico/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Ratas , Tirosina/metabolismo , Receptor del Glutamato Metabotropico 5/metabolismo , Sinapsis/metabolismo , Ratones , Humanos , Neuronas/metabolismoRESUMEN
Previous studies have rarely investigated the role of non-vitamin K oral anticoagulants (NOAC) and warfarin in the secondary prevention of ischemic stroke patients with nonvalvular atrial fibrillation (NVAF). In this study, we compared the effectiveness and safety of NOAC and warfarin for secondary prevention in Korean ischemic stroke patients with NVAF. Based on the Korean National Health Insurance Service Database, this study included 21,064 oral anticoagulants-naïve acute ischemic stroke patients with NVAF between July 2015 and June 2019. The main study outcomes included ischemic stroke, systemic embolism, major bleeding, and death. During the observational periods, NOAC users had a significantly decreased risk of ischemic stroke + systemic embolism (adjusted hazard ratio [aHR] 0.86; 95% confidence interval [CI] 0.78-0.95), ischemic stroke (aHR 0.89; 95% CI 0.81-0.99), major bleeding (aHR 0.78; 95% CI 0.68-0.89), and all-cause death (aHR 0.87; 95% CI 0.81-0.93). Standard-dose NOAC users had a lower risk of ischemic stroke, systemic embolism, and major bleeding events than warfarin users. In contrast, low-dose NOAC users did not differ in risk from warfarin users for all outcomes. In conclusion, NOACs were associated with a lower risk of secondary thromboembolic events and bleeding complications in Korean ischemic stroke patients with NVAF than warfarin.
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Anticoagulantes , Fibrilación Atrial , Accidente Cerebrovascular Isquémico , Prevención Secundaria , Warfarina , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Masculino , Femenino , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Accidente Cerebrovascular Isquémico/prevención & control , Accidente Cerebrovascular Isquémico/etiología , Anciano , Warfarina/administración & dosificación , Warfarina/uso terapéutico , Warfarina/efectos adversos , Prevención Secundaria/métodos , Administración Oral , Persona de Mediana Edad , República de Corea/epidemiología , Anciano de 80 o más Años , Hemorragia/inducido químicamente , Resultado del Tratamiento , Embolia/prevención & control , Embolia/etiologíaRESUMEN
Human advancements in agriculture, urbanization, and industrialization have led to various forms of environmental pollution, including heavy metal pollution. Insects, as highly adaptable organisms, can survive under various environmental stresses, which induce oxidative damage and impair antioxidant systems. To investigate the peroxidase (POX) family in Tenebrio molitor, we characterized two POXs, namely TmPOX-iso1 and TmPOX-iso2. The full-length cDNA sequences of TmPox-iso1 and TmPox-iso2 respectively consisted of an open reading frame of 1815 bp encoding 605 amino acids and an open reading frame of 2229 bp encoding 743 amino acids. TmPOX-iso1 and TmPOX-iso2 homologs were found in five distinct insect orders. In the phylogenetic tree analysis, TmPOX-iso1 was clustered with the predicted POX protein of T. castaneum, and TmPOX-iso2 was clustered with the POX precursor protein of T. castaneum. During development, the highest expression level of TmPox-iso1 was observed in the pre-pupal stage, while that of TmPox-iso2 expression were observed in the pre-pupal and 4-day pupal stages. TmPox-iso1 was primarily expressed in the early and late larval gut, while TmPox-iso2 mRNA expression was higher in the fat bodies and Malpighian tubules. In response to cadmium chloride treatment, TmPox-iso1 expression increased at 3 hours and then declined until 24 hours, while in the zinc chloride-treated group, TmPox-iso1 expression peaked 24 hours after the treatment. Both treated groups showed increases in TmPox-iso2 expression 24 hours after the treatments.
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Tenebrio , Animales , Humanos , Tenebrio/genética , Peroxidasas/genética , Filogenia , Proteínas/genética , Aminoácidos/genéticaRESUMEN
BACKGROUND: The South Korean government has been actively involved in plans to combat dementia, implementing a series of national strategies and plans since 2008. In July 2014, eligibility for mandatory long-term care insurance (LTCI) was extended to people with dementia enabling access to appropriate long-term care including the cognitive function training program and home nursing service. This study aimed to investigate changes in treatment patterns for Alzheimer's disease (AD) between July 2011 and June 2017 which spanned the 2014 revision. METHODS: This multicenter, retrospective, observational study of patients with newly diagnosed AD analyzed electronic medical records from 17 general hospitals across South Korea. Based on their time of AD diagnosis, subjects were categorized into Cohort 1 (1 July 2011 to 30 June 2014) and Cohort 2 (1 July 2014 to 30 June 2017). RESULTS: Subjects (N=3,997) divided into Cohorts 1 (n=1,998) and 2 (n=1,999), were mostly female (66.4%) with a mean age of 84.4 years. Cohort 1 subjects were significantly older (P<0.0001) and had a lower number of comorbidities (P=0.002) compared with Cohort 2. Mean Mini-Mental State Examination (MMSE) scores in Cohorts 1 and 2 at the time of AD diagnosis or start of initial treatment were 16.9 and 17.1, respectively (P=0.2790). At 1 year, mean MMSE scores in Cohorts 1 and 2 increased to 17.9 and 17.4, respectively (P=0.1524). Donepezil was the most frequently administered medication overall (75.0%), with comparable rates between cohorts. Rates of medication persistence were ≥98% for acetylcholinesterase inhibitor or memantine therapy. Discontinuation and switch treatment rates were significantly lower (49.7% vs. 58.0%; P<0.0001), and mean duration of initial treatment significantly longer, in Cohort 2 vs. 1 (349.3 vs. 300.2 days; P<0.0001). CONCLUSIONS: Comparison of cohorts before and after revision of the national LTCI system for dementia patients found no significant difference in mean MMSE scores at the time of AD diagnosis or start of initial treatment. The reduction in the proportion of patients who discontinued or changed their initial treatment, and the significant increase in mean duration of treatment, were observed following revision of the LTCI policy which enabled increased patient access to long-term care.
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Enfermedad de Alzheimer , Humanos , Femenino , Anciano de 80 o más Años , Masculino , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/tratamiento farmacológico , Estudios Retrospectivos , Acetilcolinesterasa/uso terapéutico , Donepezilo/uso terapéutico , Inhibidores de la Colinesterasa/uso terapéuticoRESUMEN
Mealworms beetles, Tenebrio molitor, are the limelight next-generation food for humans due to their high nutrient contents. Since Tenebrio molitor is used as feed for pets and livestock in addition to their ability to decompose polystyrene and plastic waste, it is recognized as an insect with an industrial core value. Therefore, it is important to study the immune mechanism related to the development and infection of mealworms for mass breeding purposes. The immune deficiency (Imd) signaling is one of the main pathways with pivotal roles in the production of antimicrobial peptides (AMPs). Transforming growth factor-ß activated kinase (TAK1) is one of the Imd pathway components, forms a complex with TAK1 binding protein 2 (TAB2) to ultimately help activate the transcription factor Relish and eventually induce host to produce AMPs. Relatively, little has been revealed about TAK1 in insect models, especially in the T. molitor. Therefore, this study was conducted to elucidate the function of TmTak1 in T. molitor. Our results showed that the highest and lowest mRNA expression of TmTak1 were found in egg and young larvae respectively. The tissue-specific expression patterns were reported in the gut of T. molitor larvae and the fat bodies of adults. Systemic microbial challenge illustrated TmTak1 high expression following the fungal infection in all dissected tissues except for the whole body. However, silencing TmTak1 experiments showed that the survivability of T. molitor larvae affected significantly following Escherichia coli infection. Accordingly, AMP induction after TmTak1 knock down was mainly reported in the integument and the fat bodies.
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Escarabajos , Tenebrio , Animales , Humanos , Fitomejoramiento , Escarabajos/metabolismo , Larva/genética , Regulación de la Expresión Génica , Proteínas Adaptadoras Transductoras de Señales/metabolismoRESUMEN
Background: Chronic kidney disease is a significant health burden worldwide, with increasing incidence. Although several genome-wide association studies (GWAS) have investigated single nucleotide polymorphisms (SNP) associated with kidney trait, most studies were focused on European ancestry. Methods: We utilized clinical and genetic information collected from the Korean Genome and Epidemiology Study (KoGES). Results: More than five million SNPs from 58,406 participants were analyzed. After meta-GWAS, 1,360 loci associated with estimated glomerular filtration rate (eGFR) at a genome-wide significant level (p = 5 × 10-8) were identified. Among them, 399 loci were validated with at least one other biomarker (blood urea nitrogen [BUN] or eGFRcysC) and 149 loci were validated using both markers. Among them, 18 SNPs (nine known ones and nine novel ones) with 20 putative genes were found. The aggregated effect of genes estimated by MAGMA gene analysis showed that these significant genes were enriched in kidney-associated pathways, with the kidney and liver being the most enriched tissues. Conclusion: In this study, we conducted GWAS for more than 50,000 Korean individuals and identified several variants associated with kidney traits, including eGFR, BUN, and eGFRcysC. We also investigated functions of relevant genes using computational methods to define putative causal variants.
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PURPOSE: Humulus japonicus (HJ) is one of the most important causes of weed pollinosis in East Asia. The 10 kDa protein with pI 10 in 2-dimensional gel has been recognized as the representative major allergen of HJ, but its major allergens have not been characterized. This study aimed to characterize the major allergen of HJ. METHODS: A major allergen in Japanese hop was detected by proteome analysis; it was purified to homogeneity and its sequence was obtained by transcriptome analysis. The recombinant proteins were produced in Escherichia coli and Pichia expression systems, and their immunoglobulin E (IgE) reactivities were compared to those of the natural counterpart. We also analyzed post-translational modifications such as glycosylation and phosphorylation. RESULTS: Pectin methylesterase inhibitor, Hum j 6, was found to be the major allergen of HJ, and in silico signal peptide prediction corresponds to a 15.1 kDa protein with a theoretical pI of 8.28. Natural Hum j 6 was recognized by IgE antibodies from 86.4% (19/22) of HJ pollinosis patients, whereas the recombinant proteins did not show strong IgE reactivity. No glycosylation was detected, while at least 15 phosphorylated amino acids, possibly causing the pI and molecular weight shift, were detected by tandem mass spectrometry analysis. CONCLUSIONS: Hum j 6 was identified as the representative major allergen of HJ and seems to be modified significantly after translation. These findings are useful for the development of component-resolved diagnosis and immunotherapy.
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Two forms of plasticity, synaptic and intrinsic, are neural substrates for learning and memory. Abnormalities in homeostatic plasticity cause severe neuropsychiatric diseases, such as schizophrenia and autism. This suggests that the balance between synaptic transmission and intrinsic excitability is important for physiological function in the brain. Despite the established role of synaptic plasticity between parallel fiber (PF) and Purkinje cell (PC) in fear memory, its relationship with intrinsic plasticity is not well understood. Here, patch clamp recording revealed depression of intrinsic excitability in PC following auditory fear conditioning (AFC). Depressed excitability balanced long-term potentiation of PF-PC synapse to serve homeostatic regulation of PF-evoked PC firing. We then optogenetically manipulated PC excitability during the early consolidation period resulting in bidirectional regulation of fear memory. Fear conditioning-induced synaptic plasticity was also regulated following optogenetic manipulation. These results propose intrinsic plasticity in PC as a novel mechanism of fear memory and elucidate that decreased intrinsic excitability in PC counterbalances PF-PC synaptic potentiation to maintain fear memory in a normal range.
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BACKGROUND: Ticks are ectoparasites capable of directly damaging their hosts and transmitting vector-borne diseases. The ixodid tick Haemaphysalis flava has a broad distribution that extends from East to South Asia. This tick is a reservoir of severe fever with thrombocytopenia syndrome virus (SFTSV) that causes severe hemorrhagic disease, with cases reported from China, Japan and South Korea. Recently, the distribution of H. flava in South Korea was found to overlap with the occurrence of SFTSV. METHODS: This study was undertaken to discover the molecular resources of H. flava female ticks using the Illumina HiSeq 4000 system, the Trinity de novo sequence assembler and annotation against public databases. The locally curated Protostome database (PANM-DB) was used to screen the putative adaptation-related transcripts classified to gene families, such as angiotensin-converting enzyme, aquaporin, adenylate cyclase, AMP-activated protein kinase, glutamate receptors, heat shock proteins, molecular chaperones, insulin receptor, mitogen-activated protein kinase and solute carrier family proteins. Also, the repeats and simple sequence repeats (SSRs) were screened from the unigenes using RepeatMasker (v4.0.6) and MISA (v1.0) software tools, followed by the designing of SSRs flanking primers using BatchPrimer 3 (v1.0) software. RESULTS: The transcriptome produced a total of 69,822 unigenes, of which 46,175 annotated to the homologous proteins in the PANM-DB. The unigenes were also mapped to the EuKaryotic Orthologous Groups (KOG), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) specializations. Promiscuous presence of protein kinase, zinc finger (C2H2-type), reverse transcriptase, and RNA recognition motif domains was observed in the unigenes. A total of 3480 SSRs were screened, of which 1907 and 1274 were found as tri- and dinucleotide repeats, respectively. A list of primer sequences flanking the SSR motifs was detailed for validation of polymorphism in H. flava and the related tick species. CONCLUSIONS: The reference transcriptome information on H. flava female ticks will be useful for an enriched understanding of tick biology, its competency to act as a vector and the study of species diversity related to disease transmission.
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Perfilación de la Expresión Génica , Ixodidae , Femenino , Animales , Anotación de Secuencia Molecular , Transcriptoma , Genoma , Ixodidae/genética , Repeticiones de MicrosatéliteRESUMEN
P-type Cu-Se thin films were deposited on glass substrates at room temperature using radio frequency magnetron sputtering by a single multi-component CuSe2 target. When using a multi-component target, the impact of the sputtering power on the homogeneity and stoichiometry within the thin films should be investigated in the depth direction to demonstrate a secondary effect on the electrical and optical properties of the thin films. Systematic characterization of the Cu-Se thin films, including the morphology, microstructure, chemical composition, and depth-directional chemical bonding state and defect structure of the thin films, revealed that the sputtering power played an important role in the homogeneity and stoichiometry of the thin films. At very low and very high sputtering power levels, the Cu-Se thin films exhibited more deviations from stoichiometry, while an optimized sputtering power resulted in more homogenous thin films with improved stoichiometry across the entire thin film thickness in the X-ray photoelectron spectroscopy depth profile, despite showing Se deficiency at all depths. A rapid decrease in carrier concentration, indicating a reduction in the net effect of total defects, was obtained at the optimized sputtering power with less deviation from stoichiometry in the Cu-Se thin films and the closest stoichiometric ratio at an intermediate depth.
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In tauopathy conditions, such as Alzheimer's disease (AD), highly soluble and natively unfolded tau polymerizes into an insoluble filament; however, the mechanistic details of this process remain unclear. In the brains of AD patients, only a minor segment of tau forms ß-helix-stacked protofilaments, while its flanking regions form disordered fuzzy coats. Here, it is demonstrated that the tau AD nucleation core (tau-AC) sufficiently induced self-aggregation and recruited full-length tau to filaments. Unexpectedly, phospho-mimetic forms of tau-AC (at Ser324 or Ser356) show markedly reduced oligomerization and seeding propensities. Biophysical analysis reveal that the N-terminus of tau-AC facilitates the fibrillization kinetics as a nucleation motif, which becomes sterically shielded through phosphorylation-induced conformational changes in tau-AC. Tau-AC oligomers are efficiently internalized into cells via endocytosis and induced endogenous tau aggregation. In primary hippocampal neurons, tau-AC impaired axon initial segment plasticity upon chronic depolarization and is mislocalized to the somatodendritic compartments. Furthermore, it is observed significantly impaired memory retrieval in mice intrahippocampally injected with tau-AC fibrils, which corresponds to the neuropathological staining and neuronal loss in the brain. These findings identify tau-AC species as a key neuropathological driver in AD, suggesting novel strategies for therapeutic intervention.
Asunto(s)
Enfermedad de Alzheimer , Ratones , Humanos , Animales , Proteínas tau/metabolismo , Encéfalo/metabolismo , Neuronas/metabolismo , FosforilaciónRESUMEN
Atomic layer deposition (ALD) is emerging as an efficient tool for the precise manufacture of catalysts, owing to its sophisticated surface tailoring capabilities. To overcome the techno-economic limitations of fuel cell electric vehicles (FCEVs), which are considered suitable alternatives to battery electric vehicles (BEVs), the development of cost-efficient high-performance catalysts is essential. In this study, we successfully fabricated a Pt-free cathode for a hydroxide exchange membrane fuel cell (HEMFC) with excellent oxygen reduction activity under extremely low loading of Ag electrocatalysts using ALD. Microstructural analysis confirmed that the surface modification by ALD-Ag nanoparticles exhibited excellent step coverage characteristics on porous carbon nanotubes (CNTs). An HEMFC comprising a CNT cathode surface-decorated with ALD-Ag nanoparticles delivered a high peak power density of 2154 mW mgAg-1 in an alkaline environment at 65 °C. This study demonstrates the applicability of ALD for the manufacture of highly active low-cost electrocatalysts for high-performance HEMFCs.