RESUMEN
Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons and neuroinflammation. Recent studies have identified a role of T cells in the pathogenesis of PD. Additionally, these studies suggested that α-synuclein (α-Syn) is related to abnormal T-cell responses and may act as an epitope and trigger autoimmune T-cell responses. However, it is unclear whether the α-Syn-mediated autoimmune response occurs and whether it is related to neuronal cell death and glial cell activation. In this study, we investigated the autoimmune T-cell response induced by α-Syn peptides and evaluated the neurotoxic effect of the α-Syn peptide-mediated autoimmune response. The immunization of mice with α-Syn peptides resulted in enhanced autoimmune responses, such as the peptide recall response, polarization toward Th1/Th17 cells, and regulatory T cell imbalance. Furthermore, the α-Syn autoimmune response led to the death of primary neurons cocultured with splenocytes. Treatment with conditioned media from α-Syn peptide-immunized splenocytes induced microglia and toxic A1-type astrocyte activation. Taken together, our results provide evidence of the potential role of the α-Syn-initiated autoimmune response and its contribution to neuronal cell death and glial cell activation.
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Autoinmunidad , Muerte Celular , Neuronas , alfa-Sinucleína , Animales , alfa-Sinucleína/inmunología , alfa-Sinucleína/metabolismo , Ratones , Muerte Celular/efectos de los fármacos , Neuronas/inmunología , Neuronas/metabolismo , Neuronas/patología , Neuroglía/inmunología , Neuroglía/metabolismo , Neuroglía/efectos de los fármacos , Enfermedad de Parkinson/inmunología , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/metabolismo , Ratones Endogámicos C57BL , Humanos , Activación de Linfocitos/inmunología , Activación de Linfocitos/efectos de los fármacos , Péptidos/inmunología , Células Cultivadas , Femenino , Linfocitos T Reguladores/inmunologíaRESUMEN
Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated with a high risk of mortality in immunocompromised individuals, while most patients who die of SFTS exhibit symptoms of severe encephalitis before death. However, the region of brain damage and mechanisms by which the SFTS virus (SFTSV) causes encephalitis remains unknown. Here, we revealed that SFTSV infects the brainstem and spinal cord, which are regions of the brain associated with respiratory function, and motor nerves in IFNAR1-/- mice. Further, we show that A1-reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV-infected IFNAR1-/- mice also induced neuronal cell death through the activation of A1-reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflammation in the brain regions important for respiratory function and motor nerve, which may underlie mortality in SFTS patients. This study provides new insights for the treatment of SFTS, for which there is currently no therapeutic approach.
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Astrocitos , Infecciones por Bunyaviridae , Ratones Noqueados , Phlebovirus , Receptor de Interferón alfa y beta , Animales , Astrocitos/virología , Astrocitos/patología , Ratones , Receptor de Interferón alfa y beta/genética , Receptor de Interferón alfa y beta/deficiencia , Phlebovirus/genética , Phlebovirus/fisiología , Phlebovirus/patogenicidad , Infecciones por Bunyaviridae/virología , Infecciones por Bunyaviridae/patología , Infecciones por Bunyaviridae/inmunología , Encéfalo/virología , Encéfalo/patología , Encéfalo/inmunología , Médula Espinal/virología , Médula Espinal/patología , Modelos Animales de Enfermedad , Neuronas/virología , Neuronas/patología , Ratones Endogámicos C57BL , Tronco Encefálico/virología , Tronco Encefálico/patología , Muerte CelularRESUMEN
In this study, the nonclinical pharmacokinetics of OLX702A-075-16, an RNA interference (RNAi) therapeutic currently in development, were investigated. OLX702A-075-16 is a novel N-acetylgalactosamine conjugated asymmetric small-interfering RNA (GalNAc-asiRNA) used for the treatment of an undisclosed liver disease. Its unique 16/21-mer asymmetric structure reduces nonspecific off-target effects without compromising efficacy. We investigated the plasma concentration, tissue distribution, metabolism, and renal excretion of OLX702A-075-16 following a subcutaneous administration in mice and rats. For bioanalysis, high-performance liquid chromatography with fluorescence detection (HPLC-FD) was used. The results showed rapid clearance from plasma (0.5 to 1.5 h of half-life) and predominant distribution to the liver, and/or kidney. Less than 1% of the liver concentration of OLX702A-075-16 was detected in the other tissues. Metabolite profiling using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) revealed that the intact duplex OLX702A-075-16 was the major compound in plasma. The GalNAc moiety was predominantly metabolized from the sense strand in the liver, with the unconjugated sense strand of OLX702A-075-16 accounting for more than 95% of the total exposure in the rat liver. Meanwhile, the antisense strand was metabolized by the sequential loss of nucleotides from the 3'-terminus by exonuclease, with the rat liver samples yielding the most diverse truncated forms of metabolites. Urinary excretion over 96 h was less than 1% of the administered dose in rats. High plasma protein binding of OLX702A-075-16 likely inhibited its clearance through renal filtration. Significance Statement This study presents the first comprehensive characterization of the in vivo pharmacokinetics of GalNAc-asiRNA. The pharmacokinetic insights gained from this research will aid in understanding toxicology and efficacy, optimizing delivery platforms, and improving the predictive power of preclinical species data for human applications.
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OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a risk factor for cognitive impairment, and reduced heart rate variability (HRV) has been correlated with cognitive impairment in elderly individuals. This study investigated risk factors and validated a predictive model for mild cognitive impairment (MCI) in patients with T2DM using an autonomic function test. METHODS: Patients with T2DM, 50-85 years of age, who attended the diabetes clinic at Gyeongsang National University Hospital between March 2018 and December 2019, were included. A total of 201 patients had been screened; we enrolled 124 patients according to the inclusion and exclusion criteria in this study. Cognitive function was assessed using the Montreal Cognitive Assessment-Korean version (MOCA-K); MCI was defined as a total MOCA-K score ≤ 23. Risk factors for MCI in patients with T2DM, including demographic- and diabetes-related factors, and autonomic function test results, were analyzed. Based on multivariate logistic regression, a nomogram was developed as a prediction model for MCI. RESULTS: Thirty-nine of 124 patients were diagnosed with MCI. Age, education, and decreased cardiovagal function were associated with a high risk for MCI, with cardiovagal function exerting the greatest influence. However, diabetes-related factors, such as glycemic control, duration of diabetes, or medications, were not associated with the risk for MCI. The nomogram demonstrated excellent discrimination (area under the curve, 0.832) and was well calibrated. CONCLUSION: Approximately one-third of patients had MCI; as such, carefully evaluating cognitive function in elderly T2DM patients with reduced HRV is important to prevent progression to dementia.
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Disfunción Cognitiva , Diabetes Mellitus Tipo 2 , Humanos , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/diagnóstico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Anciano , Masculino , Femenino , Persona de Mediana Edad , Anciano de 80 o más Años , Frecuencia Cardíaca/fisiología , Sistema Nervioso Autónomo/fisiopatología , Factores de RiesgoRESUMEN
The effect of transcranial direct current stimulation (tDCS) for cerebellar-dominant multiple-system atrophy (MSA-C) is not well elucidated, yet. This study aimed to investigate the effect of tDCS on the primary motor cortex (M1) and cerebellum in patients with MSA-C. We recruited probable MSA-C patients and performed three single sessions of tDCS at each visit in random order (M1, cerebellum or sham). Cerebellar ataxia was evaluated with the International Cooperative Ataxia Rating Scale (ICARS) and objective gait and static balance analyses both before and after each stimulation session. Additionally, we also evaluated the factors related with objective improvement from each stimulation. Sixteen participants were enrolled, and one dropped out after 2 sessions of stimulation due to consent withdrawal. The gait velocity, step time and single support time all significantly improved after the M1 and cerebellar tDCS treatment compared with the sham stimulation while there was no difference in the improvement of ICARS and posturography results among 3 stimulations. In terms of the related factors with improvement of gait velocity, the disease duration, baseline gait speed and single support times were correlated after M1 stimulation, while a higher ICARS score and baseline gait speed in cerebellar stimulation. There were no adverse effects reported after the tDCS sessions. Our results demonstrated that both M1 and cerebellar tDCS demonstrated benefits for MSA-C patients without significant complications. Considering the different related factors with improvement at each stimulation, the mechanism would be different between M1 and cerebellar stimulations.
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Ataxia Cerebelosa , Atrofia de Múltiples Sistemas , Estimulación Transcraneal de Corriente Directa , Humanos , Estimulación Transcraneal de Corriente Directa/métodos , Estudios Cruzados , Cerebelo/fisiología , Ataxia/terapia , Método Doble CiegoRESUMEN
BACKGROUND: The emergence of carbapenem-resistant Enterobacterales (CRE) infections is rapidly increasing and represents a serious public threat. In 2020, a total of 16,883 carbapenemase-producing Enterobacterales strains were collected; among these isolates, 21 strains were repeatedly isolated in a local tertiary care hospital. METHODS: Antimicrobial susceptibility testing was performed using the broth microdilution method. All 21 strains of CRKP were analyzed by PFGE after XbaI digestion. The 21 CRKP strains were sequenced on the Illumina Miseq and Oxford Nanopore GridION platforms. RESULTS: These 21 CRKP isolates showed an identical antimicrobial resistance profile, including resistance to ampicillin, carbapenems, cephems, chloramphenicol, fluoroquinolone, macrolides and trimethoprim/sulfamethoxazole. Based on whole-genome analysis, these 21 CRKP isolates shared a common genetic structure (ISAba125-IS630-blaNDM-1-bleMBL) and harbored additional resistance determinants (blaOXA-1, blaCTX-M-15, blaSHV-11, blaSHV-67, aac(6')-Ib-cr, qnrS1, OqxA, OqxB, catB3, mph(A), sul1, and dfrA12) and mutations in the quinolone resistance-determining regions of gyrA (S83I) and parC (S80I). These isolates belonged to the ST147 and KL64 capsular types, which were carried on IncFIB replicon plasmids. The 21 CRKP strains collected from one hospital were divided into five PFGE patterns, and they were closely related with a minimum similarity value of 95.2%. These isolates were found to be highly related based on the presence of between 2 and 27 SNPs. CONCLUSIONS: These findings indicate that NDM-1-producing K. pneumoniae ST147 may have been introduced via a common source, implying nosocomial transmission; furthermore, continuous monitoring is necessary to prevent endemic transmission.
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Enterobacteriaceae Resistentes a los Carbapenémicos , Klebsiella pneumoniae , Humanos , Klebsiella pneumoniae/genética , Centros de Atención Terciaria , República de Corea/epidemiología , Antibacterianos/farmacología , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Carbapenémicos/farmacologíaRESUMEN
BACKGROUND: Social anxiety disorder (SAD) is characterized by anxiety regarding social situations, avoidance of external social stimuli, and negative self-beliefs. Virtual reality self-training (VRS) at home may be a good interim modality for reducing social fears before formal treatment. This study aimed to find neurobiological evidence for the therapeutic effect of VRS. METHODS: Fifty-two patients with SAD were randomly assigned to a VRS or waiting list (WL) group. The VRS group received an eight-session VRS program for 2 weeks, whereas the WL group received no intervention. Clinical assessments and functional magnetic resonance imaging scanning with the distress and speech evaluation tasks were repeatedly performed at baseline and after 3 weeks. RESULTS: The post-VRS assessment showed significantly decreased anxiety and avoidance scores, distress index, and negative evaluation index for 'self', but no change in the negative evaluation index for 'other'. Patients showed significant responses to the distress task in various regions, including both sides of the prefrontal regions, occipital regions, insula, and thalamus, and to the speech evaluation task in the bilateral anterior cingulate cortex. Among these, significant neuronal changes after VRS were observed only in the right lingual gyrus and left thalamus. CONCLUSIONS: VRS-induced improvements in the ability to pay attention to social stimuli without avoidance and even positively modulate emotional cues are based on functional changes in the visual cortices and thalamus. Based on these short-term neuronal changes, VRS can be a first intervention option for individuals with SAD who avoid society or are reluctant to receive formal treatment.
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Fobia Social , Realidad Virtual , Ansiedad , Trastornos de Ansiedad , Miedo , Humanos , Fobia Social/terapiaRESUMEN
Noroviruses cause acute gastroenteritis with symptoms of diarrhoea and vomiting, and their high infectivity allows outbreaks to readily occur. Quickly identifying and isolating potential contaminants is an effective method to prevent the spread of outbreaks. A total of 376 samples collected from nine outbreaks were categorized as either patient, asymptomatic individual, cook or environmental samples, according to the source of contamination. Using real-time PCR and sequencing analysis, norovirus GII genotypes were detected in 34·9% of samples from patients, 19·2% from asymptomatic individuals, 2·4% from the environment and 1·4% from cooks. Our findings showed contrasting results in samples categories quantified based on the limit of blank and detection limit by reverse transcription droplet digital PCR, which is a more sensitive testing method than real-time-PCR.
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Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Infecciones por Caliciviridae/epidemiología , Brotes de Enfermedades , Heces , Gastroenteritis/epidemiología , Genotipo , Humanos , Norovirus/genética , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodosRESUMEN
A Gram-stain-negative, oxidase-positive, catalase-positive, aerobic, orange-pigmented, rod-shaped and non-motile bacterium designated strain MMS17-SY002T was isolated from island soil. The isolate grew at 20-37 °C (optimum, 30 °C), at pH 6.0-9.5 (optimum, pH 7) and in the presence of 0.5-4.0â% (w/v) NaCl (optimum, 2.0â%). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain MMS17-SY002T was mostly related to the genus Muriicola of the family Flavobacteriaceae and had highest sequence similarity of 96.82â% to Muriicola marianensis A6B8T and Muriicola jejuensis EM44T, but formed a distinct phylogenetic line within the genus. Chemotaxonomic analyses showed that menaquinone 6 was the predominant isoprenoid quinone, the major fatty acids were iso-C15â:â1 G and iso-C15â:â0, and the diagnostic polar lipid was phosphatidylethanolamine. The genomic DNA G+C content was 42.4 mol%. Strain MMS17-SY002T could be distinguished from related species by the combination of trypsin, α-chymotrypsin, acid phosphatase, naphthol-AS-BI-phosphohydrolase, α-galactosidase, ß-galactosidase and ß-glucosidase activities. The orthologous average nucleotide identity between the genomes of strain MMS17-SY002T and M. jejuensis and that between the strain and M. marianensis A6B8T were 73.26 and 73.33%, respectively, thus confirming the separation of the strain from related species at species level. Based on the phenotypic, phylogenetic, chemotaxonomic and genomic characterization, MMS17-SY002T should be recognized as a novel species of the genus Muriicola, for which the name Muriicola soli sp. nov. is proposed. The type strain is MMS17-SY002T (=KCTC 62790T=JCM 32370T).
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Flavobacteriaceae/clasificación , Filogenia , Microbiología del Suelo , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Flavobacteriaceae/aislamiento & purificación , Islas , Fosfatidiletanolaminas/química , Pigmentación , ARN Ribosómico 16S/genética , República de Corea , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
BACKGROUND: Although iron dyshomeostasis is associated with Parkinson's disease (PD) pathogenesis, the relationship between iron deposition and non-motor involvement in PD is not fully understood. In this study, we investigated basal ganglia and extra-basal ganglia system iron contents and their correlation with non-motor symptoms in drug-naïve, early-stage PD patients. METHODS: We enrolled 14 drug-naïve, early-stage PD patients and 12 age/sex-matched normal controls. All participants underwent brain magnetic resonance imaging to obtain the effective transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM). Deep brain structures, including the nucleus accumbens, caudate nucleus, putamen, globus pallidus, thalamus, hippocampus, and amygdala, were delineated using the FSL-FIRST; the substantia nigra, red nucleus, and dentate nucleus were segmented manually. Inter-group differences in R2* and QSM values, as well as their association with clinical parameters of PD, were investigated. RESULTS: Substantia nigra and putamen R2* values were significantly higher in PD patients than in normal controls, despite no significant difference in QSM values. Regarding the non-motor symptom scales, PD sleep scale score negatively correlated with R2* values in the red nucleus and right amygdala, Scales for Outcomes in Parkinson's disease-Autonomic scores were positively correlated with R2* values in the right amygdala and left hippocampus, and cardiovascular sub-score of Non-Motor Symptoms Scale for PD was positively associated with the QSM value in the left hippocampus. CONCLUSION: In this study, iron content in the extra-basal ganglia system was significantly correlated with non-motor symptoms, especially sleep problems and dysautonomia, even in early-stage PD.
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Enfermedad de Parkinson , Preparaciones Farmacéuticas , Ganglios Basales/diagnóstico por imagen , Humanos , Hierro , Imagen por Resonancia Magnética , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Sustancia NegraRESUMEN
Gravel is used in railway infrastructure to reduce environmental impacts and noise, but gravel on tracks must be replaced continuously because it deforms due to wear and weathering. It is therefore necessary to review the entire railroad life cycle. In this study, an unmanned aerial vehicle (UAV) was used to measure resuspended dust over a wide area. The dust was generated from transport movements in relation to the operation of a quarry, which represents the first stage of the railway life cycle. The dust was measured at Gangwon-do quarry using a Sniffer4D module, which can provide measurements at 1 s intervals through a light scattering method and has high reliability (R2 = 0.95 for PM2.5, R2 = 0.88 for PM10). The hourly generation of fugitive dust was calculated as 2937.5 g/h for PM2.5 and 4293.2 g/h for PM10. The social cost of dust generation was calculated as KRW 36.59 billion. The amount of dust generated per hour at the quarry was ~12 times greater than that generated by the operation of a regulator as a maintenance vehicle, with the largest amount of fugitive dust generated by the washing-type vehicle. This is the first study to measure the amount of fugitive dust generated in real time at 1 s intervals by monitoring the first stage of the railroad life cycle over a wide area using a Sniffer4D module attached to a UAV. This method can be replicated for use in various studies.
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Transcriptional regulator KAISO plays a critical role in cell cycle arrest and apoptosis through modulation of p53 acetylation by histone acetyltransferase p300. KAISO potently stimulates apoptosis in cells expressing WT p53, but not in p53-mutant or p53-null cells. Here, we investigated how KAISO transcription is regulated by p53, finding four potential p53-binding sites (p53-responsive DNA elements; p53REs) located in a distal 5'-upstream regulatory element, intron 1, exon 2 coding sequence, and a 3'-UTR region. Transient transcription assays of pG5-p53RE-Luc constructs with various p53REs revealed that p53 activates KAISO (ZBTB33) transcription by acting on p53RE1 (-4326 to -4227) of the 5'-upstream region and on p53RE3 (+2929 to +2959) of the exon 2 coding region during early DNA damage responses (DDRs). ChIP and oligonucleotide pulldown assays further disclosed that p53 binds to the p53RE1 and p53RE3 sites. Moreover, ataxia telangiectasia mutated (ATM) or ATM-Rad3-related (ATR) kinase-mediated p53 phosphorylation at Ser-15 or Ser-37 residues activated KAISO transcription by binding its p53RE1 or p53RE3 sites during early DDR. p53RE1 uniquely contained three p53-binding half-sites, a structural feature important for transcriptional activation by phosphorylated p53 Ser-15·Ser-37. During the later DDR phase, a KAISO-mediated acetylated p53 form (represented by a p53QRQ acetyl-mimic) robustly activated transcription by acting on p53RE1 in which this structural feature is not significant, but it provided sufficient KAISO levels to confer a p53 "apoptotic code." These results suggest that the critical apoptosis regulator KAISO is a p53 target gene that is differently regulated by phosphorylated p53 or acetylated p53, depending on DDR stage.
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Apoptosis , Factores de Transcripción/metabolismo , Activación Transcripcional , Proteína p53 Supresora de Tumor/metabolismo , Acetilación , Células Cultivadas , Humanos , Fosforilación , Factores de Transcripción/genéticaRESUMEN
Even in the face of physiological DNA damage or expression of the tumor suppressor protein p53, B cell CLL/lymphoma 6 (BCL6) increases proliferation and antagonizes apoptotic responses in B cells. BCL6 represses TP53 transcription and also appears to inactivate p53 at the protein level, and additional findings have suggested negative mutual regulation between BCL6 and p53. Here, using Bcl6-/- knockout mice, HEK293A and HCT116 p53-/- cells, and site-directed mutagenesis, we found that BCL6 interacts with p53 and thereby inhibits acetylation of Lys-132 in p53 by E1A-binding protein p300 (p300), a modification that normally occurs upon DNA damage-induced cellular stress and whose abrogation by BCL6 diminished transcriptional activation of p53 target genes, including that encoding caspase-1. Conversely, we also found that BCL6 protein is degraded via p53-induced, caspase-mediated proteolytic cleavage, and the formation of a BCL6-p53-caspase-1 complex. Our results suggest that p53 may block oncogenic transformation by decreasing BCL6 stability via caspase-1 up-regulation, whereas aberrant BCL6 expression inactivates transactivation of p53 target genes, either by inhibiting p53 acetylation by p300 or repressing TP53 gene transcription. These findings have implications for B cell development and lymphomagenesis.
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Linfocitos B/metabolismo , Caspasa 1/sangre , Transformación Celular Neoplásica/metabolismo , Regulación Enzimológica de la Expresión Génica , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Linfocitos B/patología , Caspasa 1/genética , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Células HCT116 , Células HEK293 , Humanos , Ratones , Ratones Noqueados , Proteínas Proto-Oncogénicas c-bcl-6/genética , Proteína p53 Supresora de Tumor/genéticaRESUMEN
The use of multigene panel testing for patients with a predisposition to breast/ovarian cancer is increasing as the identification of variants is useful for diagnosis and disease management. We identified pathogenic and likely pathogenic (P/LP) variants of high-and moderate-risk genes using a 23-gene germline cancer panel in 518 patients with hereditary breast and ovarian cancers (HBOC). The frequency of P/LP variants was 12.4% (64/518) for high- and moderate-penetrant genes, namely, BRCA2 (5.6%), BRCA1 (3.3%), CHEK2 (1.2%), MUTYH (0.8%), PALB2 (0.8%), MLH1 (0.4%), ATM (0.4%), BRIP1 (0.4%), TP53 (0.2%), and PMS2 (0.2%). Five patients possessed two P/LP variants in BRCA1/2 and other genes. We also compared the results from in silico splicing predictive tools and exon splicing patterns from patient samples by analyzing RT-PCR product sequences in six P/LP intronic variants and two intronic variants of unknown significance (VUS). Altered transcriptional fragments were detected for P/LP intronic variants in BRCA1, BRIP1, CHEK2, PARB2, and PMS2. Notably, we identified an in-frame deletion of the BRCA1 C-terminal (BRCT) domain by exon skipping in BRCA1 c.5152+6T>C-as known VUS-indicating a risk for HBOC. Thus, exon splicing analysis can improve the identification of veiled intronic variants that would aid decision making and determination of hereditary cancer risk.
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Proteína BRCA1/genética , Neoplasias de la Mama/genética , Proteínas de Neoplasias/genética , Neoplasias Ováricas/genética , Adulto , Neoplasias de la Mama/patología , Quinasa de Punto de Control 2/genética , Exones/genética , Proteínas del Grupo de Complementación de la Anemia de Fanconi/genética , Femenino , Mutación de Línea Germinal/genética , Humanos , Persona de Mediana Edad , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/genética , Neoplasias Ováricas/patología , ARN Helicasas/genéticaRESUMEN
A polyphasic study was carried out to establish the taxonomic position of an acidophilic isolate designated MMS16-CNU292T (=JCM 32302T) from pine grove soil, and provisionally assigned to the genus Kitasatospora. On the basis of 16S rRNA gene sequence similarity, the strain formed a novel evolutionary lineage within Kitasatospora and showed highest similarities to Kitasatospora azatica KCTC 9699T (98.75â%), Kitasatospora kifunensis IFO 15206T (98.74â%), Kitasatospora purpeofusca NRRL B-1817T (98.61â%) and Kitasatospora nipponensis HKI 0315T (98.42â%), respectively. Strain MMS16-CNU292T possessed MK-9(H6) and MK-9(H8) as the major menaquinones, and a major amount of meso-diaminopimelic acid in the cell-wall peptidoglycan. The whole-cell hydrolysates were rich in galactose, glucose and mannose, and the polar lipids mainly consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol and phosphatidylinositol mannosides. The major fatty acids were anteiso-C15â:â1-A, anteiso-C15â:â0, and iso-C15â:â0, and the DNA G+C content was 71.5 mol%. The strain exhibited antibacterial activity against a number of bacterial strains, and the activity was generally greater when grown in acidic conditions. The phylogenetic, chemotaxonomic and phenotypic properties enabled distinction of MMS16-CNU292T from related species, and thus the isolate should be recognized as a new species of the genus Kitasatospora, for which the name Kitasatospora acidiphila sp. nov. (type strain=MMS16-CNU292T=KCTC 49011T=JCM 32302T) is proposed.
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Filogenia , Pinus/microbiología , Microbiología del Suelo , Streptomycetaceae/clasificación , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Grasos/química , Bosques , Peptidoglicano/química , Fosfolípidos/química , ARN Ribosómico 16S/genética , República de Corea , Análisis de Secuencia de ADN , Streptomycetaceae/aislamiento & purificación , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
Three aerobic, rod-shaped actinobacterial strains, designated MMS17-SY117T, MMS17-SY207-3T and MMS17-SY213T, were isolated from soil and their taxonomic positions were analysed using a polyphasic approach. The isolates showed best growth at 30 °C, pH 7 and 0-1â% (w/v) NaCl. On the basis of 16S rRNA gene sequence similarity, the isolates were affiliated to the genus Nocardioides, and the closest species to MMS17-SY117T, MMS17-SY207-3T and MMS17-SY213T were Nocardioides aestuarii JC2056T (97.76%), Nocardioides currus IB-3T (97.41%) and Nocardioides exalbidus RC825T (98.71%), respectively. Each isolate formed a distinct cluster within the Nocardioides clade in the phylogenetic tree. The orthologous average nucleotide identity and digital DNA-DNA hybridization values were in the range of 74.4-85.7â% and 16.6-39.2â%, respectively, with the type strains of related species. The major polar lipids in all three strains were phosphatidylinositol, phosphatidylglycerol and diphosphatidylglycerol. The predominant fatty acids were iso-C16â:â0 and C17â:â1 ω8c. MK-8(H4) was the major isoprenoid quinone and ll-DAP was the major diamino acid. Galactose, glucose and rhamnose were present in the whole-cell hydrolysate, and MMS17-SY213T also contained mannose and ribose. The DNA G+C contents of MMS17-SY117T, MMS17-SY207-3T and MMS17-SY213T were 72.2, 70.4 and 71.5 mol%, respectively. The phylogenetic, phenotypic and chemotaxonomic data supported the classification of each strain as representing a new species of Nocardioides, for which the names Nocardioides euryhalodurans sp. nov. (MMS17-SY117T=KCTC 49175T=JCM 32831T), Nocardioides seonyuensis sp. nov. (MMS17-SY207-3T=KCTC 49176T=JCM 32832T) and Nocardioides eburneiflavus sp. nov. (MMS17-SY213T=KCTC 49177T=JCM 32833T) are proposed accordingly.
Asunto(s)
Actinobacteria/clasificación , Filogenia , Microbiología del Suelo , Actinobacteria/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Grasos/química , Hibridación de Ácido Nucleico , Fosfolípidos/química , ARN Ribosómico 16S/genética , República de Corea , Arena/microbiología , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
Vibrio parahaemolyticus is a marine bacterium that causes foodborne diarrhea. Many seafood restaurants keep live fish and shellfish in fish tanks for use in raw seafood dishes; thus, the present study aimed to investigate the prevalence, antibiotic-resistance, and virulence characteristics exhibited by V. parahaemolyticus detected in restaurant fish-tank water samples collected in Seoul, South Korea. Fish-tank water samples were collected from 69 restaurants in Seoul, and screened for the presence of V. parahaemolyticus via both a commercial detection kit, and a real-time polymerase chain reaction (RT-PCR) to detect the toxR gene. Antibiotic susceptibility and virulence determinants of V. parahaemolyticus isolates were evaluated and identified using standard disk-diffusion and RT-PCR methods, respectively. Thirty-five (50.7%) of the 69 analyzed water samples were found to be contaminated with V. parahaemolyticus. Those isolates were most often resistant to ampicillin (51.4% of isolates), followed by amikacin and tetracycline (11.4%), and ceftazidime (8.6%). Thirty (85.7%) out of the 35 isolates carried all four cytotoxicity-inducing type III secretion system 1 (T3SS1) genes [specifically, 34 (97.1%), 33 (94.3%), 35 (100%), and 32 (91.4%) isolates carried genes encoding the VP1670, VP1686, VP1689, and VP1694 T3SS1 proteins, respectively]. The type VI secretion systems (T6SS1 and T6SS2) genes were also detected in 11 (31.4%) and 27 (77.1%) isolates, respectively. However, virulence determinants such as the hemolysin (tdh and trh), urease (ureC), T3SS2α, or T3SS2ß genes that are known to be associated with enterotoxicity were not detected in all isolates. Although some known major virulence genes were not detected in the V. parahaemolyticus isolates, the results of this study indicate that restaurant fish tanks are a potential source of antibiotic-resistant V. parahaemolyticus. The presented data support the need for strict guidelines to regulate the maintenance of restaurant fish tanks to prevent antibiotic-resistant foodborne vibriosis.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Agua de Mar/microbiología , Vibrio parahaemolyticus/efectos de los fármacos , Factores de Virulencia/genética , Proteínas Bacterianas/genética , ADN Bacteriano , Proteínas de Unión al ADN/genética , Contaminación de Alimentos , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Restaurantes , Alimentos Marinos/microbiología , Seúl , Factores de Transcripción/genética , Vibrio parahaemolyticus/clasificación , Vibrio parahaemolyticus/aislamiento & purificación , VirulenciaRESUMEN
Recent advances in next-generation sequencing technologies have uncovered the genetic backgrounds of various diseases. Type 1 sialidosis (OMIM#256550) is a rare autosomal recessive lysosomal storage disease caused by a mutation in the NEU1 (OMIM * 608272) gene. In this study, we aimed to review the previous reports of type 1 sialidosis and compare those with the first case of type 1 sialidosis in Korea. A 36-year-old woman presented with progressive ataxia, myoclonus, and seizure since the age of 12. Whole-exome sequencing revealed a pathogenic missense variant c.928G > A (p.D310N) and novel c.15_16del (p.P6Qfs*21) of the NEU1 gene as final causal candidate as compound heterozygotes. We reviewed the literature and selected the clinical reports of genetically confirmed type 1 sialidosis patients. A total of 45 patients in 17 reports were identified. Cherry-red spot, myoclonus, ataxia, and seizure were reported in 51.2%, 100.0%, 87.8%, and 73.7% of patients, respectively. Abnormalities of cognitive function, EEG, and brain MRI and visual symptoms were reported in 22.2%, 40.7%, 66.7%, and 70.2% of patients, respectively. Overall, our patient showed similar clinical features to previous type 1 sialidosis patients, but she did not complain of visual symptoms despite having cherry-red spots. We summarize the clinical features of type 1 sialidosis and report the first case of type 1 sialidosis with novel deletion variant in the NEU1 gene in the Korean population. Our study suggests the importance of ophthalmologic examinations in patients with myoclonus, ataxia, and seizure who do not complain of visual symptoms.
Asunto(s)
Mucolipidosis/genética , Neuraminidasa/genética , Adulto , Femenino , Humanos , Mutación MissenseRESUMEN
A novel actinobacterial strain producing an antifungal substance was isolated from a sample of acidic mine area soil, and its taxonomic position was evaluated. The novel strain, designated TW1S1T, formed white-grey aerial mycelium and yellow substrate mycelium on oatmeal agar. Growth occurred at 10-45â°C (optimum, 30â°C), pH 4-9 (pH 6-7) and in the presence of up to 8â% (w/v) NaCl. Melanin was produced on peptone-yeast extract-iron agar. Phylogenetic analysis based on its 16S rRNA gene sequence indicated that the novel strain should be assigned to the genus Streptomyces, and the closest species was Streptomyces puniciscabiei S77T with 99.1â% sequence similarity, which was followed by Streptomyces durhamensis NRRL B-3309T (99.0â%), Streptomyces filipinensis NBRC 12860T (98.9â%) and Streptomyces yaanensis Z4T (98.7â%). The chemotaxonomic properties were consistent with those of Streptomyces. ll-Diaminopimelic acid was the diagnostic diamino acid, and alanine, glutamic acid and glycine were present in the peptidoglycan. The cell-wall hydrolysate also contained galactose, glucose, mannose and ribose. The predominant isoprenoid quinones were MK-9(H4) and MK-9(H6), the major polar lipids were phosphatidylglycerol and an unidentified phospholipid, and the main fatty acids were iso-C16â:â0 and anteiso-C15â:â0. However, strain TW1S1T could be distinguished from its neighbouring species by its phenotypic properties. In addition, the genome-based comparison with the closest species indicated that strain TW1S1T should be recognized as a separate species. The phylogenetic, phenotypic and chemotaxonomic as well as genomic evidence supported that TW1S1T represents a novel species of Streptomyces, for which the name Streptomycesfodineus sp. nov. is proposed (type strain, TW1S1T = KCTC 49013T = JCM 32404T).
Asunto(s)
Minería , Filogenia , Microbiología del Suelo , Streptomyces/clasificación , Antibiosis , Antifúngicos , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Grasos/química , Peptidoglicano/química , Fosfolípidos/química , Pigmentación , ARN Ribosómico 16S/genética , República de Corea , Análisis de Secuencia de ADN , Streptomyces/aislamiento & purificación , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
Three Gram-negative, non-spore-forming, rod-shaped and motile bacterial strains, designated MMS16-UL250T, MMS16-UL253T and MMS16-UL482T, were isolated from coastal seawater and subjected to taxonomic characterization. All isolates grew at 4-30 °C (optimum, 25 °C), at pH 6-10 (pH 7) and in the presence of up to 8â% NaCl (2.5-4.5â%). The 16S rRNA gene sequence similarities between the three isolates and Shewanella algicola St-6T, the closest species, were 98.1-99.2â%, and those among the isolates were 98.5-99.0â%. In the phylogenetic tree, MMS16-UL250T formed a cluster with S. algicola St-6T, but the DNA-DNA relatedness between the two strains was 28.8±1.5â%, thus confirming their separation at species level. The other two strains formed separate phylogenetic lines respectively. The main quinones for all strains were Q-7, Q-8, MK-7 and MMK-7, which is typical for Shewanella. The major polar lipids of all strains were phosphatidylglycerol and phosphatidylethanolamine, and the common major fatty acid was a summed feature consisting of C16â:â1ω7c and/or C16â:â1ω6c while the proportions varied among the three strains. The DNA G+C contents of the strains also varied between 42.1 and 43.7 mol%. Phenotypic properties distinguished each strain from S. algicola as well as from one another. Based on the polyphasic analysis, each strain is considered to represent a novel species of Shewanella, for which the names Shewanellasaliphila sp. nov. (type strain, MMS16-UL250T=KCTC 62131T=JCM 32304T), Shewanella ulleungensis sp. nov. (type strain, MMS16-UL253T=KCTC 62130T=JCM 32305T) and Shewanella litoralis sp. nov. (type strain, MMS16-UL482T=KCTC 62129T=JCM 32306T) are proposed.