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Prohibitin 1 (PHB1) is ubiquitously expressed in multiple compartments within cells and is involved in the cell cycle, cell signaling, apoptosis, transcriptional regulation, and mitochondrial biogenesis at the cellular level and in the inflammation-associated and immunological functions of B and T lymphocytes. PHB1 is an important protein that performs antioxidant regulation and immune functions inside and outside cells but has not been sufficiently studied in teleost fish. Our study aimed to elucidate the functional properties and gain new insights into the biological processes and immune system of red seabream (Pagrus major), a commercially important fish cultured in South Korea and East Asia. PHB1 mRNA was most abundantly expressed in the head kidney of healthy red seabream, and significant changes in its expression were observed after artificial infection with bacteria and viruses. On analysis, reporter gene was also significantly upregulated by polyinosinic-polycytidylic acid, lipopolysaccharides, and hydrogen peroxide. Consequent to the functional characterization of PHB1 in cells via recombinant protein preparation, the activity of leukocytes was enhanced and the reactive oxygen species-induced stress in red blood cells was reduced. The results reveal the functional characteristics of PHB1 and provide new insights into the biological processes and immune system of P. major, with beneficial implications in the study of stress responses.
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Doenças dos Peixes , Proteínas de Peixes , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Imunidade Inata , Proibitinas , Proteínas Repressoras , Animais , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteínas Repressoras/imunologia , Doenças dos Peixes/imunologia , Imunidade Inata/genética , Regulação da Expressão Gênica/imunologia , Perfilação da Expressão Gênica/veterinária , Poli I-C/farmacologia , Filogenia , Dourada/imunologia , Dourada/genética , Infecções por Vírus de DNA/imunologia , Infecções por Vírus de DNA/veterinária , Sequência de Aminoácidos , Alinhamento de Sequência/veterinária , Lipopolissacarídeos/farmacologia , Perciformes/imunologia , Perciformes/genética , Iridoviridae/fisiologia , Vibrio/fisiologiaRESUMO
Accurate origin determination of seafood is crucial for consumer trust and safety. This study was performed to develop a machine learning-based single-nucleotide polymorphism (SNP) analysis technique to determine the origin of Acetes species in salted small-shrimp products. Mitochondrial DNA (COI and 16S rRNA) analysis revealed genetic variations among species and origins. Eight candidate SNPs were identified, six of which were developed into markers for genotyping analysis. Using the developed markers, an SNP array was created and SNP data from salted small-shrimp samples were obtained. Machine learning analysis using a supervised learning algorithm achieved 100% accuracy in classifying the origin of Acetes based on SNP data. This method offers a reliable method for regulatory bodies to combat food fraud and ensure product integrity. The approach can be further improved by expanding the data set to encompass a wider range of species and origins. This study highlights the potential of SNP analysis and machine learning for ensuring seafood authenticity and promoting sustainable practices.
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The EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2) is involved in connective tissue development, elastic fiber formation, and tumor growth. In this study, we characterized the cDNA of EFEMP2 (PoEFEMP2), a member of the fibulin family of ECM proteins, in the olive flounder Paralichthys olivaceus. The coding region of PoEFEMP2 encodes a protein that contains six calcium-binding EGF-like (EGF-CA) domains and four complement Clr-like EGF-like (cEGF) domains. PoEFEMP2 shows 67.51-96.77 % similarities to orthologs in a variety of fish species. PoEFEMP2 mRNA was detected in all tissues examined; the highest levels of PoEFEMP2 mRNA expression were observed in the heart, testis, ovary and muscle. The PoEFEMP2 mRNA level increases during early development. In addition, the PoEFEMP2 mRNA level increased at 3 h post-infection (hpi) and decreased from 6 to 48 hpi in flounder Hirame natural embryo (HINAE) cells infected with viral hemorrhagic septicemia virus (VHSV). Disruption of PoEFEMP2 using the clustered regularly interspaced short palindromic repeats/CRISPR-associated-9 (CRISPR/Cas9) system resulted in a significant upregulation of VHSV G mRNA levels and immune-related genes expression in knockout cells. These findings implicate PoEFEMP2 in antiviral responses in P. olivaceus.
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Sequência de Aminoácidos , Proteínas da Matriz Extracelular , Proteínas de Peixes , Regulação da Expressão Gênica , Septicemia Hemorrágica Viral , Imunidade Inata , Novirhabdovirus , Filogenia , Animais , Novirhabdovirus/fisiologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/imunologia , Septicemia Hemorrágica Viral/imunologia , Septicemia Hemorrágica Viral/genética , Imunidade Inata/genética , Regulação da Expressão Gênica/imunologia , Alinhamento de Sequência/veterinária , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Perfilação da Expressão Gênica/veterinária , Linguados/imunologia , Linguados/genéticaRESUMO
A Gram-stain-positive, aerobic bacterium, designated as YPD9-1T, was isolated from the gut contents of a spotty belly greenling, Hexagrammos agrammus, collected near Dokdo island, South Korea. The rod-shaped cells were oxidase-positive, and catalase-negative. The major cellular fatty acids were anteiso-C15â:â0, iso-C15â:â0, C16â:â0, iso-C16â:â0 and iso-C17: 0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and two unidentified lipids. The DNA G+C content was 47.6 mol% and the predominant respiratory quinone was menaquinone MK-7. The 16S rRNA gene sequence of YPD9-1T showed low sequence similarities to species of the genus Paenibacillus, Paenibacillus pocheonensis Gsoil 1138T (97.21â% of sequence similarity), Paenibacillus aestuarii CJ25T (97.12â%) and Paenibacillus allorhizoplanae JJ-42T (96.89â%). The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that YPD9-1T formed a distinct branch among other species of the genus Paenibacillus. The digital DNA-DNA hybridisation, average nucleotide identity, and average amino acid identity values between YPD9-1T and the related species were in the ranges of 15.3-16.2â%, 74.1-78.4â%, and 71.1-71.9â%, respectively, which are below the species cutoff values. On the basis of the results of the polyphasic analysis, we conclude that strain YPD9-1T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus hexagrammi sp. nov. is proposed. The type strain of Paenibacillus hexagrammi is YPD9-1T (=KCTC 43424T =LMG 32988T).
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Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Paenibacillus , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Vitamina K 2 , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , República da Coreia , Ácidos Graxos/análise , Ácidos Graxos/química , Paenibacillus/isolamento & purificação , Paenibacillus/classificação , Paenibacillus/genética , Vitamina K 2/análogos & derivados , Vitamina K 2/análise , Animais , Hibridização de Ácido Nucleico , Fosfolipídeos/análise , Fosfolipídeos/químicaRESUMO
BACKGROUND: Dermatophytosis is a common and major public health concern worldwide. Despite the increasing availability of antifungal drugs, relapses and untreated cases of dermatophyte infections are reported. Therefore, novel antifungal agents are required. Aminopyrrolnitrin (APRN) shows promise for dermatophytosis treatment because of its antifungal activity. OBJECTIVES: This study aimed to assess the antifungal properties of APRN against Trichophyton verrucosum (T. verrucosum), in both laboratory settings and a guinea pig model. METHODS: The minimum inhibitory concentrations (MICs) of APRN and enilconazole against T. verrucosum were determined according to the CLSI M38 method. The skins of 16 male guinea pigs were infected with 1.0 × 108 conidia of T. verrucosum and the animals were grouped into sets of four: negative control group (NC) received normal saline; positive control group (PC) received 2 µg/mL of enilconazole; and APRN4 and APRN8 received 4 and 8 µg/mL of APRN, respectively. Clinical, mycological and histological efficacies were measured after 10 days. RESULTS: The MIC90 of APRN and enilconazole against T. verrucosum was 4 and 2 µg/mL, respectively. The clinical scores of PC, APRN4, and APRN8 were significantly lower than those of NC. Clinical and mycological efficacies were higher for APRN8, APRN4 and PC. No fungi were observed in the skin tissues of APRN4 and APRN8, while fungi were observed in 50% of the PC. CONCLUSION: APRN showed antifungal activity against T. verrucosum in vitro and in vivo and is a potential candidate for the treatment of dermatophytosis.
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Antifúngicos , Modelos Animais de Doenças , Testes de Sensibilidade Microbiana , Tinha , Trichophyton , Animais , Cobaias , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Trichophyton/efeitos dos fármacos , Tinha/tratamento farmacológico , Tinha/microbiologia , Masculino , Pele/microbiologiaRESUMO
Aminopyrrolnitrin (APRN), a natural halogenated phenylpyrrole derivative (HPD), has strong antifungal and antiparasitic activities. Additionally, it showed 2.8-fold increased photostability compared to pyrrolnitrin, a commercially available HPD with antimicrobial activity. For microbial production of APRN, we first engineered anthranilate phosphoribosyltransferase encoded by trpD from Corynebacterium glutamicum, resulting in a TrpDA162D mutation that exhibits feedback-resistant against L-tryptophan and higher substrate affinity compared to wild-type TrpD. Plasmid-borne expression of trpDA162D in C. glutamicum TP851 strain with two copies of trpDA162D in the genome led to the production of 3.1 g/L L-tryptophan in flask culture. Subsequent step for L-tryptophan chlorination into 7-chloro-L-tryptophan was achieved by introducing diverse sources of genes encoding tryptophan 7-halogenase (PrnA or RebH) and flavin reductase (Fre, PrnF, or RebF). The combined expression of prnA from Serratia grimesii or Serratia plymuthica with flavin reductase gene from Escherichia coli, Pseudomonas fluorescens, or Lechevalieria aerocolonigenes yielded higher production of 7-chloro-L-tryptophan in comparison to other sets of two-component systems. In the next step, production of putative monodechloroaminopyrrolnitrin (MDAP) from 7-chloro-L-tryptophan was achieved through the expression of prnB encoding MDAP synthase from S. plymuthica or P. fluorescens. Finally, an artificial APRN biosynthetic pathway was constructed by simultaneously expressing genes coding for tryptophan 7-halogenase, flavin reductase, MDAP synthase, and MDAP halogenase (PrnC) from different microbial sources within the L-tryptophan-producing TP851 strain. As prnC from S. grimesii or S. plymuthica was introduced into the host strain, which carried plasmids expressing prnA from S. plymuthica, fre from E. coli, and prnB from S. plymuthica, APN3639 and APN3638 accumulated 29.5 mg/L and 28.1 mg/L of APRN in the culture broth. This study represents the first report on the fermentative APRN production by metabolically engineered C. glutamicum.
Assuntos
Corynebacterium glutamicum , Engenharia Metabólica , Corynebacterium glutamicum/metabolismo , Corynebacterium glutamicum/genética , Engenharia Metabólica/métodos , Pirrolnitrina/biossíntese , Pirrolnitrina/metabolismo , Fermentação , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Triptofano/biossíntese , Triptofano/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , OxirredutasesRESUMO
Myostatin (MSTN, also known as growth differentiation factor-8 (GDF-8)), a member of the transforming growth factor ß (TGF-ß) superfamily, functions as a negative regulator of skeletal muscle development and growth. However, it is also expressed in a wide range of tissues in fish and thus may have more diverse roles in this group than in mammals. In this study, we assessed the genome-wide transcriptional expression pattern associated with the CRISPR/Cas9-mutated MSTN gene in the olive flounder (Paralichthys olivaceus) in association with changes in cell proliferation and transportation processes. There were no differences in the hepatosomatic index, and the growth of male and female fish increased in the F1 progeny of the MSTN mutants. Furthermore, the histopathological analysis showed that myostatin editing resulted in a 41.24% increase in back muscle growth and 46.92% increase in belly muscle growth in male flounder compared with normal flounder, and a 16.01% increase in back muscle growth and 14.26% increase in belly muscle growth in female flounder compared with normal flounder. This study demonstrates that editing of the myostatin gene enhances muscle growth in olive flounder, with a notably more pronounced effect observed in males. Consequently, myostatin-edited male flounder could represent a valuable asset for the flounder aquaculture industry.
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Linguado , Músculo Esquelético , Miostatina , Animais , Miostatina/genética , Miostatina/metabolismo , Masculino , Feminino , Linguado/genética , Linguado/crescimento & desenvolvimento , Linguado/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Desenvolvimento Muscular/genética , Edição de Genes , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Sistemas CRISPR-Cas , MutaçãoRESUMO
BACKGROUND: Benign convulsions with mild gastroenteritis (CwG) are prevalent in young children during the winter. Early in the coronavirus disease 2019 (COVID-19) pandemic, viral gastroenteritis occurrence decreased and seasonal variation was lost, which can change CwG. PURPOSE: Here we investigated changes in frequency, seasonal variation, and causative viruses of CwG during the COVID-19 pandemic. METHODS: We screened 1134 patients (3-36 months) with "other and unspecified convulsions" treated at Chonnam National University Hospital between March 2017 and February 2023; of them, we enrolled 41 (3.6%) with CwG. We compared their medical records from period I (March 2017 to February 2020) to those from period II (March 2020 to February 2023). Publicly available viral gastroenteritis surveillance data from the Korea Disease Control and Prevention Agency (KDCA) were reviewed as reference. RESULTS: Of the 41 patients with CwG, 18 (2.9% of 613) were affected in period I versus 23 (4.4% of 512) in period II (P=0.184). In period I, CwG mainly occurred in winter and spring (55.6% and 22.2%, respectively). In period II, there were fewer CwG cases (39.1%) in winter and more cases in summer and autumn (26.1% and 17.4%, respectively): the cases of norovirus genogroup II (GII)-associated CwG increased significantly in the summer (38.5% vs. 0%, P= 0.046). Norovirus GII was the most common virus (56.1% of isolates). Enteric adenovirus was the second most common (19.5%), with one case in period I and 7 cases in period II (P=0.059). The clinical characteristics of enteric adenovirus-associated CwG were similar to those of norovirus. Seasonal changes in and viral causes of CwG were consistent with those observed in the KDCA stool surveillance data. CONCLUSION: During the COVID-19 pandemic, CwG frequency did not change, seasonal variation was unapparent, and enteric adenovirus-associated CwG frequency increased.
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Red sea bream iridovirus (RSIV) is a highly contagious viral infection that affects various fish species and poses a significant threat to the global aquaculture industry. Thus, accurate and timely diagnosis is paramount for sustainable management of fish health. This study rigorously evaluated the diagnostic efficacy of various polymerase chain reaction (PCR) assays, focusing on those recommended by the World Organization for Animal Health (WOAH) and the assays newly proposed by WOAH's Aquatic Animals Health Standards Commission. Specifically, this study assessed conventional PCR, nested PCR, modified 1-F/1-R, and real-time PCR assays using a 95% limit of detection (LoD95%), as well as diagnostic sensitivity (DSe) and specificity (DSp) tests across different RSIV severity grades (G0-G4). In previous studies, the LoD95% for the 1-F/1-R and 4-F/4-R conventional assays were 225.81 and 328.7 copies/reaction, respectively. The modified 1-F/1-R exhibited a lower LoD95% of 51.32 copies/reaction. Notably, the nested PCR had an LoD95% of 11.23 copies/reaction, and the real-time PCR assay had an LoD95% of 12.02 copies/reaction. The DSe varied across RSIV severity grades, especially in the lower G0-G2 grades. The nested PCR and modified 1-F/1-R assays displayed the highest DSe, making them particularly useful for early-stage screening and detection of asymptomatic carriers. In addition, the PCR assays did not cross-react with any other aquatic pathogens except RSIV. Our findings significantly advanced the diagnostic capabilities of RSIVD by suggesting that nested PCR and modified 1-F/1-R assays are particularly promising for early detection. We propose their inclusion in future WOAH guidelines for a more comprehensive diagnostic framework.
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Doenças dos Peixes , Iridovirus , Dourada , Viroses , Animais , Iridovirus/genética , Reação em Cadeia da Polimerase em Tempo Real/veterináriaRESUMO
Surgical techniques are gaining attention for treating physical diseases in aquaculture and aquarium fish. Sturgeon is a suitable species for surgical experiments due to its industrial significance. Maintaining homeostasis is crucial during surgical procedures, and the liver plays a major role in immune regulation. High temperature is suggested to improve physiological activity and wound healing. This study investigated differences in hepatectomy sturgeons' tolerance and histopathological responses of internal organs. Moreover, this study investigated the effects of high temperatures on wound healing and hematopoietic recovery in fish undergoing surgical procedures. The liver condition was found to play a pivotal role in the analysis, and cortisol levels were affected by anesthesia. The results showed that high temperature facilitated hematopoietic recovery and wound healing, but excessive induction of physiological activity caused damage. Managing high temperatures and liver conditions induced a remarkable improvement in wound healing. However, anesthesia itself can be a significant stressor for fish, and wound healing requires a greater amount of energy. Further research is needed to understand the stress factors caused by surgical procedures and anesthesia and to promote animal welfare in fishery products.
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This study detected two potential pathogens, Vibro parahaemolyticus, which causes acute hepatopancreatic necrosis disease (AHPND), and white spot syndrome virus (WSSV), in fishing bait in South Korea. However, their infectious nature was not confirmed, possibly due to the degradation caused by freezing/thawing or prolonged storage under frozen conditions. While infectivity was not confirmed in this study, there is still a significant risk of exposure to these aquatic products. Furthermore, fishing bait and feed should be handled with caution as they are directly exposed to water, increasing the risk of disease transmission. In Australia, cases of WSSV infection caused by imported shrimp intended for human consumption have occurred, highlighting the need for preventive measures. While freezing/thawing is a method for inactivating pathogens, there are still regulatory and realistic issues to be addressed.
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We explored the biotechnological applicability of a previously established olive flounder (Paralichthys olivaceus) embryonic cell line (FGBC8). FGBC8 was transfected with pEGFP-c1 and pluripotency-related genes, then infected with viral hemorrhagic septicemia virus (VHSV), and the expression of immune-related genes was observed through quantitative real-time polymerase chain reaction. Transfected cells showed strong green fluorescence 48 h after transfection, and pluripotency-related genes were successfully transfected. In addition, FGBC8 cells were highly susceptible to VHSV and the expression of immune-related genes was induced during infection. Our results demonstrate that FGBC8 cells are valuable research tools for assessing host-pathogen interactions and biotechnological applications.
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Doenças dos Peixes , Linguado , Septicemia Hemorrágica Viral , Novirhabdovirus , Animais , Linguado/genética , Análise Citogenética , Linhagem Celular , Novirhabdovirus/genéticaRESUMO
BACKGROUND: Seizures in children with coronavirus disease 2019 (COVID-19) were markedly increased during the Omicron variant surge. Most seizures occurred with fever. New-onset afebrile seizures were rarely reported; therefore, their courses are not well-known. CASE PRESENTATION: Two patients (7 and 26 months of age, respectively) with COVID-19 showed recurrent afebrile seizures immediately after resolution of a fever lasting for 2-3 days. Bilateral convulsive seizures lasted for approximately 1 min/episode (6 of 7 total episodes) and occurred 3-4 times within 2-3 h. However, the patients were alert between seizures, which is in contrast to seizures occurring with encephalopathy or encephalitis. Only one episode required acute antiseizure medication. Brain magnetic resonance imaging showed a reversible splenial lesion in one patient. The serum uric acid level was slightly increased (7.8 mg/dL) in this patient. Electroencephalography findings were all normal. During the follow-up period, no seizures or developmental problems have been observed. CONCLUSIONS: COVID-19-associated, afebrile benign convulsions with or without a reversible splenial lesion are similar to 'benign convulsions with mild gastroenteritis'; therefore, continuation of antiseizure medication does not seem necessary.
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COVID-19 , Ácido Úrico , Criança , Humanos , Recém-Nascido , COVID-19/complicações , SARS-CoV-2 , Convulsões/etiologia , Imageamento por Ressonância Magnética , Febre/etiologiaRESUMO
OBJECTIVE: Self-limited infantile epilepsy (SeLIE) has distinctive clinical features, and the PRRT2 gene is known to be a considerable genetic cause. There have been a few studies on PRRT2-positive SeLIE only, and anti-seizure medications are often required due to frequent seizures at initial seizure onset. This study aimed to provide clinical information for the early recognition of patients with PRRT2-positive SeLIE and to propose effective anti-seizure medications for seizure control. METHODS: We retrospectively reviewed 36 patients diagnosed with SeLIE with genetically confirmed pathogenic variants of PRRT2. In addition, six atypical cases with neonatal-onset seizures and unremitting after 3 years of age were included to understand the expanded clinical spectrum of PRRT2-related epilepsy. We analyzed the initial presentation, clinical course, and seizure control response to anti-seizure medications. RESULTS: Patients with PRRT2-related epilepsy had characteristic seizure semiology at the initial presentation, including all afebrile, clustered (n = 23, 63.9%), short-duration (n = 33, 91.7%), and bilateral tonic-clonic seizures (n = 26, 72.2%). Genetic analysis revealed that c. 649dupC was the most common variant, and six patients had a 16p11.2 microdeletion containing the PRRT2 gene. One-third of the patients were sporadic cases without a family history of epilepsy or paroxysmal movement disorders. In the 33 patients treated with anti-seizure medications, sodium channel blockers, such as carbamazepine, were the most effective in seizure control. SIGNIFICANCE: Our results delineated the clinical characteristics of PRRT2-positive SeLIE, differentiating it from other genetic infantile epilepsies and discovered the effective anti-seizure medications for initial clustered seizure control. If afebrile bilateral tonic-clonic seizures develop in a normally developed infant as a clustered pattern, PRRT2-positive SeLIE should be considered as a possible diagnosis, and sodium channel blockers should be administered as the first medication for seizure control.
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Epilepsia Neonatal Benigna , Epilepsia , Lactente , Recém-Nascido , Humanos , Epilepsia Neonatal Benigna/tratamento farmacológico , Epilepsia Neonatal Benigna/genética , Epilepsia Neonatal Benigna/diagnóstico , Mutação , Estudos Retrospectivos , Bloqueadores dos Canais de Sódio , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Convulsões/tratamento farmacológico , Convulsões/genéticaRESUMO
BACKGROUND: Phase I of the Korean Undiagnosed Diseases Program (KUDP), performed for 3 years, has been completed. The Phase I program aimed to solve the problem of undiagnosed patients throughout the country and develop infrastructure, including a data management system and functional core laboratory, for long-term translational research. Herein, we share the clinical experiences of the Phase I program and introduce the activities of the functional core laboratory and data management system. RESULTS: During the program (2018-2020), 458 patients were enrolled and classified into 3 groups according to the following criteria: (I) those with a specific clinical assessment which can be verified by direct testing (32 patients); (II) those with a disease group with genetic and phenotypic heterogeneity (353 patients); and (III) those with atypical presentations or diseases unknown to date (73 patients). All patients underwent individualized diagnostic processes based on the decision of an expert consortium. Confirmative diagnoses were obtained for 242 patients (52.8%). The diagnostic yield was different for each group: 81.3% for Group I, 53.3% for Group II, and 38.4% for Group III. Diagnoses were made by next-generation sequencing for 204 patients (84.3%) and other genetic testing for 35 patients (14.5%). Three patients (1.2%) were diagnosed with nongenetic disorders. The KUDP functional core laboratory, with a group of experts, organized a streamlined research pipeline covering various resources, including animal models, stem cells, structural modeling and metabolic and biochemical approaches. Regular data review was performed to screen for candidate genes among undiagnosed patients, and six different genes were identified for functional research. We also developed a web-based database system that supports clinical cohort management and provides a matchmaker exchange protocol based on a matchbox, likely to reinforce the nationwide clinical network and further international collaboration. CONCLUSIONS: The KUDP evaluated the unmet needs of undiagnosed patients and established infrastructure for a data-sharing system and future functional research. The advancement of the KUDP may lead to sustainable bench-to-bedside research in Korea and contribute to ongoing international collaboration.
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Doenças não Diagnosticadas , Bases de Dados Factuais , Humanos , Disseminação de Informação , Doenças Raras/diagnóstico , Doenças Raras/epidemiologia , Doenças Raras/genética , República da Coreia/epidemiologiaRESUMO
BACKGROUND: Most patients with developmental and epileptic encephalopathy (DEE) have genetic etiology, which has been uncovered with different methods. Although chromosomal microarray analysis (CMA) has been broadly used in patients with DEE, data is still limited. METHODS: Among 560 children (<18 years) who underwent CMA in our hospital between January 2013 and June 2021, 146 patients with developmental delay and recurrent seizures were screened. Patients with major brain abnormalities, metabolic abnormalities, and specific syndromes were excluded. The rate of rare copy number variants (CNVs) was estimated in total and according to seizure-onset age, relation to first seizure with the diagnosis of developmental delay, epilepsy syndromes, and organ anomalies. RESULTS: Among the 110 patients enrolled, the rate of rare CNVs was 16.4%, varying by seizure-onset age: 33.3% in three neonates, 21.2% in 33 infants, 13.3% in 45 early childhood patients, 5.3% in 19 late childhood patients, and 30.0% in 10 adolescents. In relation to the first seizure with the diagnosis of developmental delay, the rates were 3.7%, 22.2%, and 12.5% in "before", "after", and "concurrent" subclasses, respectively. The rates of rare CNVs were 16.7% in "other predominantly focal or multifocal epilepsy", 28.6% in "other predominantly generalized epilepsy (PGE)", and 15.4% in West syndrome. The rates were 27.8% in minor brain anomalies, 37.5% in facial dysmorphism, and 22.2%, 20.0%, and 57.1% in endocrine, genitourinary and cardiovascular anomalies, respectively. CONCLUSION: The rate of rare CNVs in patients with genetic DEE was 16.4% in total, which was higher in seizures occurring below the infantile period or after the diagnosis of developmental delay, in PGE, and in the presence of facial dysmorphism or cardiovascular anomalies.
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Encefalopatias , Variações do Número de Cópias de DNA , Epilepsia , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Encefalopatias/complicações , Encefalopatias/genética , Deficiências do Desenvolvimento/genética , Convulsões/complicações , Convulsões/genética , Epilepsia/genéticaRESUMO
Krüppel-like factor 10 (KLF10) regulates various cellular functions, such as proliferation, differentiation and apoptosis, as well as the homeostasis of several types of tissue. In the present study, we attempted a loss-of-function analysis of zebrafish Klf11a and Klf11b, which constitute human KLF10 homologs. Embryos injected with klf11b-morpholino (MO) showed developmental retardation and cell death, whereas klf11a-MO-injected embryos showed normal development. In klf11b-MO-injected embryos, a dramatic increase in the amount of zebrafish p53 mRNA might be the cause of the increase in that of bax. The degree of apoptosis decreased in the klf11b-MO and p53-MO co-injected embryos. These findings imply that KLF10 is a negative regulator of p53-dependent transcription, suggesting that the KLF10/p53 complex may play an important role in apoptosis for maintenance of tissue homeostasis during embryonic development.
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Tripartite motif-containing (TRIM) proteins are conserved throughout the metazoan kingdom, and the TRIM subset finTRIM is highly diversified in fish. We isolated TRIM16 cDNA, a member of the finTRIM family, from the olive flounder Paralichthys olivaceus (PoTRIM16). PoTRIM16 contained a 1,725-bp coding sequence encoding a 574-amino acid polypeptide, which in turn contained a really interesting new gene (RING) finger domain, B-box-type zinc finger (B-BOX), nuclease SbcCD subunit C (SbcC), structural maintenance of chromosome (SMC prok B), and stonustoxin (SNTX) subunit alpha (SPRY-PRY-SNTX). Multiple alignment of related sequences revealed that PoTRIM16 showed 86.63-97.40% identity with fish orthologues, and a phylogenetic tree was constructed of vertebrates. PoTRIM16 mRNA was detected in all tissues examined; levels were highest in the eye and ovary. PoTRIM16 mRNA expression was investigated during early development. Under VHSV infection, PoTRIM16 mRNA was downregulated in the liver of P. olivaceus. This is the first study to characterize fish-specific finTRIM in P. olivaceus, which may play a role in the immune response against virus infection.
Assuntos
Doenças dos Peixes , Linguado , Novirhabdovirus , Animais , Feminino , Novirhabdovirus/fisiologia , Filogenia , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Enteroviral meningitis is a common disease in children; however, serotype data are still lacking, especially for late childhood. OBJECTIVES: This study analyzed the number of annual cases, distribution by age group, and characteristics of each serotype among children with enteroviral meningitis. STUDY DESIGN: After the initial screening of 1,009 children (<18 years) with viral meningitis between 2008 and 2021, the data of enteroviral meningitis were retrospectively reviewed. The number of annual cases and serotypes were investigated. The distribution of serotypes across different ages was reviewed. Clinical characteristics of the major serotypes (detected in at least 15 patients) were further examined. RESULTS: Among the 700 patients with enteroviral meningitis, serotypes were tested in 517 patients (73.9%), which could be typed in 370 patients (71.6%). EV-A71 was the most common serotype detected in 2010, 2012, and 2019. After 2020, enterovirus was rarely detected. The group B coxsackieviruses (CVBs) were commonly detected in neonates (CVB1, 33.3%) and infants (CVB5, 17.4%). The echoviruses were commonly detected beyond infancy; E30 was the most frequently detected in late childhood (14.4%) and adolescents (15.4%). EV-A71 was the most frequently detected in early childhood (17.2%). Between the 11 major serotypes, vomiting, headache, and irritability were more commonly associated with echoviruses (P <0.01). In EV-A71, neurologic symptoms and skin lesions were more common (P <0.01). CONCLUSION: The CVBs were commonly detected in neonates and infants, whereas the echoviruses were commonly detected beyond infancy and caused vomiting, headache, and irritability. EV-A71 was the most frequently detected in early childhood, frequently causing neurologic and dermatologic problems.