RESUMEN
Microplastics (MPs) poses a significant threat to ecosystems and human health, demanding immediate attention. The reported research work offers an effective and low cost method towards the detection of toxic MPs. In this study, hydrophobic cerium oxide nanoparticles (CeO2 NPs) are synthesized and applied as promising electrode material for the detection of two different types of MPs, i.e. polyethylene (PE) and polypropylene (PP). Through electrochemical analyses, such as cyclic voltammetry (CV) and linear sweep voltammetry (LSV), hydrophobic CeO2 NPs modified glassy carbon electrode (GCE) based sensor demonstrated remarkable sensitivity of â¼0.0343 AmLmg-1cm-2 and detection limit of â¼0.226 mgmL-1, with promising correlation coefficient (R2) towards the detection of PE (â¼27-32 µm). Furthermore, hydrophobic CeO2 NPs modified GCE exhibited promising stability and reproducibility towards PE (â¼27-32 µm), suggesting the promising potential of hydrophobic CeO2 NPs as electrode materials for an electrochemical microplastics detection.
Asunto(s)
Cerio , Monitoreo del Ambiente , Interacciones Hidrofóbicas e Hidrofílicas , Microplásticos , Contaminantes Químicos del Agua , Cerio/química , Contaminantes Químicos del Agua/análisis , Microplásticos/análisis , Monitoreo del Ambiente/métodos , Nanopartículas/química , Técnicas Electroquímicas/métodos , Electrodos , Polietileno/química , Reproducibilidad de los Resultados , Nanopartículas del Metal/química , Polipropilenos/química , Límite de DetecciónRESUMEN
In semi-enclosed coastal brackish lakes, changes in dissolved oxygen in the bottom layer due to salinity stratification can affect the flux of phosphorus (P) at the sediment-water interface, resulting in short- and long-term water quality fluctuations in the water column. In this study, the physicochemical properties of the water layers and sediments at five sites in Saemangeum Lake were analyzed in spring and autumn for four years, and phosphorus release experiments from sediments were conducted for 20 days under oxic and anoxic conditions during the same period. Sediment total phosphorus (T-P) decreased in autumn compared to spring due to mineralization of organic bound phosphorus, which was the most dominant P fraction. This may be related to the increase in the ratio of PO4-P to T-P in bottom waters in autumn, when hypoxia was frequently observed. The difference in P fluxes between oxic and anoxic conditions indicated that during autumn, as compared to spring, the release of phosphorus could have a more immediate impact on the water column during the formation of hypoxia/anoxia. The main factors influencing changes in P fluxes from sediments were identified through redundancy analysis. Additionally, based on the results of multiple regression analysis, sediment TOC, sediment non-apatite phosphorus, porewater pH, and porewater PO4-P were determined to be the most significant factors affecting P fluxes from sediments, depending on the season or redox conditions. Recently, the increased influx of seawater into Saemangeum Lake has been shown to contribute to water quality improvements in the water column due to a strong dilution effect. However, the sediment environment has shifted towards a more reduced state, leading to increased P release under anoxic conditions. Therefore, for future water quality management within the lake, it is necessary to consistently address the recurring hypoxia and continuously monitor phosphorus dynamics.
Asunto(s)
Lagos , Contaminantes Químicos del Agua , Humanos , Lagos/química , Fósforo/análisis , Oxígeno , Monitoreo del Ambiente/métodos , Sedimentos Geológicos/química , Contaminantes Químicos del Agua/análisis , Hipoxia , ChinaRESUMEN
To investigate the effect of the predominant fungal species from Korean traditional meju and doenjang on soybean fermentation, the enzymatic activity and amino acid production of twenty-two fungal strains were assessed through solid- and liquid-state soybean fermentation. Enzymatic activity analyses of solid-state fermented soybeans revealed different enzyme activities involving protease, leucine aminopeptidase (LAP), carboxypeptidase (CaP), glutaminase, γ-glutamyl transferase (GGT), and amylase, depending on the fungal species. These enzymatic activities significantly affected the amino acid profile throughout liquid-state fermentation. Strains belonging to Mucoromycota, including Lichtheimia, Mucor, Rhizomucor, and Rhizopus, produced smaller amounts of total amino acids and umami-producing amino acids, such as glutamic acid and aspartic acid, than strains belonging to Aspergillus subgenus circumdati. The genera Penicillium and Scopulariopsis produced large amounts of total amino acids and glutamic acid, suggesting that these genera play an essential role in producing umami and kokumi tastes in fermented soybean products. Strains belonging to Aspergillus subgenus circumdati, including A. oryzae, showed the highest amino acid content, including glutamic acid, suggesting the potential benefits of A. oryzae as a starter for soybean fermentation. This study showed the potential of traditional meju strains as starters for soybean fermentation. However, further analysis of processes such as the production of G-peptide for kokumi taste and volatile compounds for flavor and safety is needed.
Asunto(s)
Aminoácidos , Alimentos de Soja , Aminoácidos/metabolismo , Alimentos de Soja/microbiología , Glycine max , Fermentación , Hongos , Aspergillus/metabolismo , Ácido Glutámico/metabolismo , Péptido Hidrolasas/metabolismoRESUMEN
Early detection and effective blood glucose control are critical for preventing and managing diabetes-related complications. Conventional glucometers provide point-in-time measurements but are painful and cannot facilitate continuous monitoring. Continuous glucose monitoring systems are comfortable but face challenges in terms of accuracy, cost, and sensor lifespan. This study aimed to develop a microneedle-based sensor patch for minimally invasive, painless, and continuous glucose monitoring in the interstitial fluid to address these limitations. Experimental results confirm painless and minimally invasive penetration of the skin tissue with cylindrical microneedles (3 × 3 array) to a depth of approximately 520 µm with minimal loading. The microneedle sensors fabricated with precision using the complementary metal-oxide semiconductor process were immobilized with glucose oxidase, as confirmed through phase angle analysis. Long-term tests confirmed the effective operation of the sensor for up to seven days. Glucose concentrations determined from the fitted concentration-impedance curves correlated well with those measured using commercial glucometers, indicating the reliability and precision of the microneedle sensor. The flexible and minimally invasive sensor developed in this study facilitates painless and continuous glucose monitoring.
Asunto(s)
Técnicas Biosensibles , Automonitorización de la Glucosa Sanguínea , Glucemia , Polímeros , Líquido Extracelular/química , Impedancia Eléctrica , Reproducibilidad de los Resultados , Agujas , Glucosa/análisisRESUMEN
Histone demethylases govern diverse cellular processes, including growth, development, and secondary metabolism. In the present study, we investigated the functions of two lysine demethylases, KdmA and KdmB, in the opportunistic human pathogenic fungus Aspergillus fumigatus. Experiments with mutants harboring deletions of genes encoding KdmA (ΔkdmA) and KdmB (ΔkdmB) showed that KdmA is necessary for normal growth and proper conidiation, whereas KdmB negatively regulates vegetative growth and conidiation. In both mutant strains, tolerance to H2O2 was significantly decreased, and the activities of both conidia-specific catalase (CatA) and mycelia-specific catalase (Cat1) were decreased. Both mutants had significantly increased sensitivity to the guanine nucleotide synthesis inhibitor 6-azauracil (6AU). The ΔkdmA mutant produced more gliotoxin (GT), but the virulence was not changed significantly in immunocompromised mice. In contrast, the production of GT and virulence were markedly reduced by the loss of kdmB. Comparative transcriptomic analyses revealed that the expression levels of developmental process-related genes and antioxidant activity-related genes were downregulated in both mutants. Taken together, we concluded that KdmA and KdmB have opposite roles in vegetative growth, asexual sporulation, and GT production. However, the two proteins were equally important for the development of resistance to 6AU.
RESUMEN
BACKGROUND AND PURPOSE: Cerebral small vessel disease is characterized by progressive cerebral white matter changes (WMCs). This study aimed to compare the effects of cilostazol and aspirin on changes in WMC volume in patients with cerebral small vessel disease. METHODS: In a multicenter, double-blind, randomized controlled trial, participants with moderate or severe WMCs and at least one lacunar infarction detected on brain magnetic resonance imaging were randomly assigned to the cilostazol and aspirin groups in a 1:1 ratio. Cilostazol slow release (200 mg) or aspirin (100 mg) capsules were administered once daily for 2 years. The primary outcome was the change in WMC volume on magnetic resonance images from baseline to 2 years. Secondary imaging outcomes include changes in the number of lacunes or cerebral microbleeds, fractional anisotropy, and mean diffusivity on diffusion tensor images, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all ischemic vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability. RESULTS: Between July 2013 and August 2016, 256 participants were randomly assigned to the cilostazol (n=127) and aspirin (n=129) groups. Over 2 years, the percentage of WMC volume to total WM volume and the percentage of WMC volume to intracranial volume increased in both groups, but neither analysis showed significant differences between the groups. The peak height of the mean diffusivity histogram in normal-appearing WMs was significantly reduced in the aspirin group compared with the cilostazol group. Cilostazol significantly reduced the risk of ischemic vascular event compared with aspirin (0.5 versus 4.5 cases per 100 person-years; hazard ratio, 0.11 [95% CI, 0.02-0.89]). CONCLUSIONS: There was no significant difference between the effects of cilostazol and aspirin on WMC progression in patients with cerebral small vessel disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01932203.
Asunto(s)
Aspirina/administración & dosificación , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/tratamiento farmacológico , Cilostazol/administración & dosificación , Imagen por Resonancia Magnética , Sustancia Blanca , Anciano , Anciano de 80 o más Años , Aspirina/efectos adversos , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/etiología , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Cilostazol/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sustancia Blanca/irrigación sanguínea , Sustancia Blanca/diagnóstico por imagenRESUMEN
Reusable, antibacterial, and photocatalytic isoporous through-hole air filtration membranes have been demonstrated based on hydrothermally grown ZnO nanorods (NRs). High-temperature (300~375 °C) stability of thermoset-based isoporous through-hole membranes has enabled concurrent control of porosity and seed formation via high-temperature annealing of the membranes. The following hydrothermal growth has led to densely populated ZnO NRs on both the membrane surface and pore sidewall. Thanks to the nanofibrous shape of the grown ZnO NRs on the pore sidewall, the membrane filters have shown a high (>97%) filtration efficiency for PM2.5 with a rather low-pressure (~80 Pa) drop. The membrane filters could easily be cleaned and reused many times by simple spray cleaning with a water/ethanol mixture solution. Further, the grown ZnO NRs have also endowed excellent bactericidal performance for both Gram-positive S. aureus and Gram-negative S. enteritidis bacteria. Owing to the wide bandgap semiconductor nature of ZnO NRs, organic decomposition by photocatalytic activity under UV illumination has been successfully demonstrated. The reusable, multifunctional membrane filters can find wide applications in air filtration and purification.
RESUMEN
The APSES family proteins are transcription factors (TFs) with a basic helix-loop-helix domain, known to regulate growth, development, secondary metabolism, and other biological processes in Aspergillus species. In the genome of the human opportunistic pathogenic fungus Aspergillus fumigatus, five genes predicted to encode APSES TFs are present. Here, we report the characterization of one of these genes, called mbsA (Afu7g05620). The deletion (Δ) of mbsA resulted in significantly decreased hyphal growth and asexual sporulation (conidiation), and lowered mRNA levels of the key conidiation genes abaA, brlA, and wetA. Moreover, ΔmbsA resulted in reduced spore germination rates, elevated sensitivity toward Nikkomycin Z, and significantly lowered transcripts levels of genes associated with chitin synthesis. The mbsA deletion also resulted in significantly reduced levels of proteins and transcripts of genes associated with the SakA MAP kinase pathway. Importantly, the cell wall hydrophobicity and architecture of the ΔmbsA asexual spores (conidia) were altered, notably lacking the rodlet layer on the surface of the ΔmbsA conidium. Comparative transcriptomic analyses revealed that the ΔmbsA mutant showed higher mRNA levels of gliotoxin (GT) biosynthetic genes, which was corroborated by elevated levels of GT production in the mutant. While the ΔmbsA mutant produced higher amount of GT, ΔmbsA strains showed reduced virulence in the murine model, likely due to the defective spore integrity. In summary, the putative APSES TF MbsA plays a multiple role in governing growth, development, spore wall architecture, GT production, and virulence, which may be associated with the attenuated SakA signaling pathway.
Asunto(s)
Aspergillus fumigatus/metabolismo , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , Esporas Fúngicas/metabolismo , Factores de Transcripción/metabolismo , Transcripción Genética , Aspergillus fumigatus/genética , Proteínas Fúngicas/genética , Genes Fúngicos , Esporas Fúngicas/genética , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: The infant brain grows quickly with elaborate microstructural development during the neonatal period. The white matter, during critical periods of development, is selectively vulnerable to altered maturation and impaired growth in very-low-birth-weight (VLBW) infants. OBJECTIVE: To evaluate whether abnormal white matter maturation in VLBW infants is associated with poor neurodevelopmental outcomes at 18 months of corrected age. METHODS: Between 2015 and 2017, we recruited 60 VLBW infants at 24-32 weeks of gestational age and 15 full-term controls. All participants underwent magnetic resonance imaging at near-term age and were assessed at 18 months of corrected age with the Bayley Scales of Infant and Toddler Development, Third Edition. The associations between regional white matter fractional anisotropy (FA) and mean diffusivity on diffusion tensor imaging (DTI) and developmental outcomes were explored using multivariable linear regression after correcting for gestational age, postmenstrual age at DTI scan, and maternal education level. RESULTS: The FA values of the splenium of the corpus callosum (p = 0.032), corticospinal tract (p = 0.025), middle cerebellar peduncle (MCP) (p < 0.001), and cingulum (p = 0.043) were significantly related to cognitive scores; however, only the association corresponding to the MCP remained significant after correcting for multiple comparisons. The MCP FA (p = 0.008) was associated with motor scores after correction for multiple comparisons (p = 0.008). Cognitive impairment (area under the curve [AUC] = 0.823, 95% confidence interval [CI] = 0.722-0.911) and motor impairment (AUC = 0.776, 95% CI = 0.656-0.899) were predicted by MCP FA. CONCLUSIONS: The FA of MCP at near-term age may predict developmental outcomes of VLBW infants at 18 months of corrected age.
Asunto(s)
Pedúnculo Cerebeloso Medio , Sustancia Blanca , Adolescente , Encéfalo/diagnóstico por imagen , Imagen de Difusión Tensora , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Sustancia Blanca/diagnóstico por imagenRESUMEN
This study aimed to elaborate upon prior findings suggestive of the altered lateralization of structural connectivity in the developing preterm brain by using diffusion tensor imaging tractography to explore how network topological asymmetries in fronto-limbic neural circuitry are altered at 36-41 weeks, postmenstrual age in 64 preterm infants without severe brain injury and 33 term-born infants. We compared the pattern of structural connectivity and network lateralization of the betweenness centrality in the medial fronto-orbital gyrus, superior temporal gyrus, amygdala, and hippocampus-the structures comprising the fronto-limbic brain circuit-between preterm and term infants. Global efficiency, local efficiency, and small-world characteristics did not differ significantly between the two hemispheres in term-born infants, suggesting that integration and segregation are balanced between the left and right hemispheres. However, the preterm brain showed significantly greater leftward lateralization of small-worldness (P = 0.033); the lateralization index of the betweenness centrality revealed that the medial fronto-orbital gyrus (P = 0.008), superior temporal gyrus (P = 0.031), and hippocampus (P = 0.028) showed significantly increased leftward asymmetry in preterm infants relative to term-infants independent of sex, age at imaging, and bronchopulmonary dysplasia. The altered lateralization of fronto-limbic brain circuitry might be involved in the early development of social-emotional disorders in preterm infants.
Asunto(s)
Encéfalo , Imagen de Difusión Tensora , Recien Nacido Prematuro , Vías Nerviosas , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Femenino , Humanos , Recién Nacido , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatologíaRESUMEN
The APSES transcription factor (TF) in Aspergillus species is known to govern diverse cellular processes, including growth, development, and secondary metabolism. Here, we investigated functions of the rgdA gene (Afu3g13920) encoding a putative APSES TF in the opportunistic human-pathogenic fungus Aspergillus fumigatus The rgdA deletion resulted in significantly decreased hyphal growth and asexual sporulation. Consistently, transcript levels of the key asexual developmental regulators abaA, brlA, and wetA were decreased in the ΔrgdA mutant compared to those in the wild type (WT). Moreover, ΔrgdA resulted in reduced spore germination rates and elevated transcript levels of genes associated with conidium dormancy. The conidial cell wall hydrophobicity and architecture were changed, and levels of the RodA protein were decreased in the ΔrgdA mutant. Comparative transcriptomic analyses revealed that the ΔrgdA mutant showed higher mRNA levels of gliotoxin (GT)-biosynthetic genes and GT production. While the ΔrgdA mutant exhibited elevated production of GT, ΔrgdA strains showed reduced virulence in the mouse model. In addition, mRNA levels of genes associated with the cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway and the SakA mitogen-activated protein (MAP) kinase pathway were increased in the ΔrgdA mutant. In summary, RgdA plays multiple roles in governing growth, development, GT production, and virulence which may involve attenuation of PKA and SakA signaling.IMPORTANCE Immunocompromised patients are susceptible to infections with the opportunistic human-pathogenic fungus Aspergillus fumigatus This fungus causes systemic infections such as invasive aspergillosis (IA), which is one of the most life-threatening fungal diseases. To control this serious disease, it is critical to identify new antifungal drug targets. In fungi, the transcriptional regulatory proteins of the APSES family play crucial roles in controlling various biological processes, including mating, asexual sporulation and dimorphic growth, and virulence traits. This study found that a putative APSES transcription factor, RgdA, regulates normal growth, asexual development, conidium germination, spore wall architecture and hydrophobicity, toxin production, and virulence in A. fumigatus Better understanding the molecular mechanisms of RgdA in human-pathogenic fungi may reveal a novel antifungal target for future drug development.
Asunto(s)
Aspergillus fumigatus/metabolismo , Aspergillus fumigatus/fisiología , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , Esporas Fúngicas/metabolismo , Factores de Transcripción/metabolismo , Aspergillus fumigatus/genética , Proteínas Fúngicas/genética , Genes Fúngicos , Esporas Fúngicas/genética , Factores de Transcripción/genética , Transcripción Genética , VirulenciaRESUMEN
OBJECTIVE: The current study examined gender-related differences in hemispheric asymmetries of graph metrics, calculated from a cortical thickness-based brain structural covariance network named hemispheric morphological network. METHODS: Using the T1-weighted magnetic resonance imaging scans of 285 participants (150 females, 135 males) retrieved from the Human Connectome Project (HCP), hemispheric morphological networks were constructed per participant. In these hemispheric morphologic networks, the degree of similarity between two different brain regions in terms of the distributed patterns of cortical thickness values (the Jensen-Shannon divergence) was defined as weight of network edge that connects two different brain regions. After the calculation and summation of global and local graph metrics (across the network sparsity levels K = 0.10-0.36), asymmetry indexes of these graph metrics were derived. RESULTS: Hemispheric morphological networks satisfied small-worldness and global efficiency for the network sparsity ranges of K = 0.10-0.36. Between-group comparisons (female versus male) of asymmetry indexes revealed opposite directionality of asymmetries (leftward versus rightward) for global metrics of normalized clustering coefficient, normalized characteristic path length, and global efficiency (all p < 0.05). For the local graph metrics, larger rightward asymmetries of cingulate-superior parietal gyri for nodal efficiency in male compared to female, larger leftward asymmetry of temporal pole for degree centrality in female compared to male, and opposite directionality of interhemispheric asymmetry of rectal gyrus for degree centrality between female (rightward) and male (leftward) were shown (all p < 0.05). CONCLUSION: Patterns of interhemispheric asymmetries for cingulate, superior parietal gyrus, temporal pole, and rectal gyrus are different between male and female for the similarities of the cortical thickness distribution with other brain regions. Accordingly, possible effect of gender-by-hemispheric interaction has to be considered in future studies of brain morphology and brain structural covariance networks.
Asunto(s)
Grosor de la Corteza Cerebral , Mapeo Encefálico , Encéfalo/fisiología , Lateralidad Funcional/fisiología , Corteza Prefrontal/fisiología , Adulto , Encéfalo/diagnóstico por imagen , Conectoma/métodos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Corteza Prefrontal/diagnóstico por imagen , Caracteres SexualesRESUMEN
South Korea's large hospitals are severely burdened by patient congestion because patients throng to these places expecting to get treated better given their higher-quality healthcare. Effective cost management of the healthcare system is one way to reduce patient congestion in a large hospital. This study proposes methods that can help direct patient flows in a desirable direction and suggests ways to effectively manage the cost of healthcare. The study also discusses how selfish patients act in ways that maximize their benefits by choosing a specific hospital and in turn forcing the hospital and the healthcare network to bear more costs than is necessary. The study proposes a model describing the need for intervention from the government to control the cost escalation resulting from selfish routing. The study proposes two heuristic algorithms to solve the suggested model. The flow-based algorithm addresses the target quantum of flows, and the utility-based algorithm targets the value of cost functions. Performances of heuristics are evaluated through numerical experiments. The utility-based algorithm yields higher values for objectives, while the flow-based algorithm controls the extent of investment. A case study based on data from the Seoul city database is also analyzed. The cost adjustment policy is compared with simple, uniformly improved network policies, and findings show that such policies have the strength needed to improve the cost-effectiveness of the healthcare system if implemented fully and effectively.
Asunto(s)
Análisis Costo-Beneficio , Costos y Análisis de Costo , Atención a la Salud/organización & administración , Economía Hospitalaria , Algoritmos , Conducta de Elección , Atención a la Salud/economía , Atención a la Salud/estadística & datos numéricos , Heurística , Hospitales/normas , Humanos , Estudios de Casos Organizacionales , República de CoreaRESUMEN
Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by a heterogeneous distribution of pathological changes in the brain. Cortical thickness is one of the most sensitive imaging biomarkers for AD representing structural atrophy. The purpose of this study is to identify novel genes associated with cortical thickness. We measured the whole-brain mean cortical thickness from magnetic resonance imaging (MRI) scans in 919 subjects from the Alzheimer's Disease Neuroimaging Initiative cohort, including 163 AD patients, 488 mild cognitive impairment patients, and 268 cognitively normal participants. Based on the single-nucleotide polymorphism (SNP)-based genome-wide association study, we performed gene-based association analysis for mean cortical thickness. Furthermore, we performed expression quantitative trait loci, protein-protein interaction network, and pathway analysis to identify biologically functional information. We identified four genes (B4GALNT1, RAB44, LOC101927583, and SLC26A10), two pathways (cyclin-dependent protein kinase holoenzyme complex and nuclear cyclin-dependent protein kinase holoenzyme complex), and one protein-protein interaction (B4GALNT1 and GALNT8 pair). These genes are involved in protein degradation, GTPase activity, neuronal loss, and apoptosis. The identified pathways are involved in the cellular processes and neuronal differentiation, which contribute to neuronal loss that is responsible for AD. Furthermore, the most significant SNP (rs12320537) in B4GALNT1 is associated with expression levels of B4GALNT1 in several brain regions. Thus, the identified genes and pathways provide deeper mechanistic insight into the molecular basis of brain atrophy in AD.
Asunto(s)
Enfermedad de Alzheimer/genética , Grosor de la Corteza Cerebral , Endofenotipos , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Neuroimagen , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , ARN Largo no Codificante/genéticaRESUMEN
BACKGROUND: Preterm infants are at risk for structural disruption of brain connectivity due to perinatal complications encountered during the fetal and neonatal periods. This study aimed to investigate the development of connectivity using diffusion tensor imaging at near-term age and the effect of grade 1 intraventricular hemorrhage on it. METHODS: A total of 86 infants (55 preterm infants, 24 full-term infants) without apparent brain injury underwent diffusion magnetic resonance imaging (MRI) between 36 and 41 weeks post-menstrual age. The diffusion-MRI based connectomics were constructed from 64-segmented regions by using the Johns Hopkins University neonate atlas and were weighted with fractional anisotropy. The connectomes were quantified in the structural networks and investigated using network metrics, such as the clustering coefficient, local efficiency, characteristic path length, global efficiency, and small-worldness. We compared the differences in the brain networks of preterm infants with or without grade 1 intraventricular hemorrhage in binary and fractional anisotropy-weighted (wFA) connectomes. RESULTS: The 55 preterm infants had a mean gestational age at birth of 29.3 ± 4.1 weeks and the 24 term-born infants, 38.1 ± 1.1 weeks. A total of 13 of the 55 preterm infants (23.6%) were diagnosed with grade 1 intraventricular hemorrhage. The development of connectivity of the brain network in preterm infants without intraventricular hemorrhage was comparable at near-term age to that in term infants. The preterm infants with germinal matrix hemorrhage exhibited higher clustering (0.093 ± 0.015 vs. 0.088 ± 0.007, p = 0.027) and local efficiency (0.151 ± 0.022 vs. 0.141 ± 0.010, p = 0.025), implying the potential for segregation. However, the preterm infants with intraventricular hemorrhage revealed a longer path length (0.291 ± 0.035 vs. 0.275 ± 0.019, p = 0.020) and lower global efficiency (3.998 ± 0.473 vs. 4.212 ± 0.281, p = 0.048), indicating a decreased integration in the wFA connectivity matrix than those without germinal matrix hemorrhage, after correcting for gestational age, sex, bronchopulmonary dysplasia, and age at scan. CONCLUSION: Grade 1 intraventricular hemorrhage in preterm infants may enhance the capacity for local information transfer and the relative reinforcement of the segregation of networks at the expense of global integration capacity.
Asunto(s)
Encéfalo/crecimiento & desarrollo , Encéfalo/patología , Hemorragia Cerebral/patología , Enfermedades del Prematuro/patología , Factores de Edad , Encéfalo/diagnóstico por imagen , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/diagnóstico por imagen , Desarrollo Infantil , Estudios de Cohortes , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/diagnóstico por imagen , MasculinoRESUMEN
Trimeric G proteins play a central role in the G protein signaling in filamentous fungi and Gα subunits are the major component of trimeric G proteins. In this study, we characterize three Gα subunits in the human pathogen Aspergillus fumigatus. While the deletion of gpaB and ganA led to reduced colony growth, the growth of the ΔgpaA strain was increased in minimal media. The germination rate, conidiation, and mRNA expression of key asexual development regulators were significantly decreased by the loss of gpaB. In contrast, the deletion of gpaA resulted in increased conidiation and mRNA expression levels of key asexual regulators. The deletion of gpaB caused a reduction in conidial tolerance against H2O2, but not in paraquat (PQ). Moreover, the ΔgpaB mutant showed enhanced susceptibility against membrane targeting azole antifungal drugs and reduced production of gliotoxin (GT). The protein kinase A (PKA) activity of the ΔganA strain was severely decreased and protein kinase C (PKC) activity was detected all strains at similar levels, indicating that all G protein α subunits of A. fumigatus may be a component of the cAMP/PKA signaling pathway and appear to possess the PKC signaling pathway as an alternative backup pathway to compensate for PKA depletion. Collectively, the three Gα subunits regulate growth, germination, asexual development, resistance to oxidative stress, and GT production differently via the PKA or PKC signaling pathway. The function of GanA of A. fumigatus was elucidated for the first time.
RESUMEN
This study aimed to investigate the efficacy of ginseng vinegar (GV) for preventing and ameliorating the obesity and inflammation. Oral administrations of GV with different doses were conducted for 10 weeks in the preventive model and therapeutic model. In the preventive model, above GV-medium dose significantly reduced body weight gain, epididymal fat weight, triglycerides, and total cholesterol compared to control. GV-high dose effectively improved the inflammatory factors (tumor necrosis factor-alpha (TNF-α) and interleukin 6) in serum, liver, and adipose tissue. In the therapeutic model, all GV groups showed significantly decreased body weight gain, epididymal fat weight, triglycerides, and total cholesterol. Reductions of the TNF-α level in the serum and liver were observed in all GV groups, and the CRP levels in the liver of all GV groups were significantly decreased with different trend from the preventive model. These results suggest that GV is more effective in therapeutic model and is a potential food for obesity and associated inflammation.
RESUMEN
The regulator of G-protein signaling (RGS) proteins play an important role in upstream control of heterotrimeric G-protein signaling pathways. In the genome of the human opportunistic pathogenic fungus Aspergillus fumigatus, six RGS protein-encoding genes are present. To characterize the rgsA gene predicted to encode a protein with an RGS domain, we generated an rgsA null mutant and observed the phenotypes of the mutant. The deletion (Δ) of rgsA resulted in increased radial growth and enhanced asexual sporulation in both solid and liquid culture conditions. Accordingly, transcripts levels of the key asexual developmental regulators abaA, brlA, and wetA are elevated in the ΔrgsA mutant. Moreover, ΔrgsA resulted in elevated spore germination rates in the absence of a carbon source. The activity of cAMP-dependent protein kinase A (PKA) and mRNA levels of genes encoding PKA signaling elements are elevated by ΔrgsA. In addition, mRNA levels of genes associated with stress-response signaling increased with the lack of rgsA, and the ΔrgsA spores showed enhanced tolerance against oxidative stressors. Comparative transcriptomic analyses revealed that the ΔrgsA mutant showed higher mRNA levels of gliotoxin (GT) biosynthetic genes. Accordingly, the rgsA null mutant exhibited increased production of GT and elevated virulence in the mouse. Conversely, the majority of genes encoding glucan degrading enzymes were down-regulated by ΔrgsA, and endoglucanase activities were reduced. In summary, RgsA plays multiple roles, governing growth, development, stress responses, virulence, and external polymer degradation-likely by attenuating PKA signaling.
Asunto(s)
Aspergilosis/microbiología , Aspergillus fumigatus/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Proteínas Fúngicas/metabolismo , Estrés Oxidativo , Proteínas RGS/metabolismo , Animales , Aspergillus fumigatus/genética , Aspergillus fumigatus/patogenicidad , Proteínas Quinasas Dependientes de AMP Cíclico/genética , Femenino , Proteínas Fúngicas/genética , Gliotoxina/biosíntesis , Ratones , Ratones Endogámicos ICR , Proteínas RGS/genética , Transducción de Señal , Transcriptoma , Virulencia/genéticaRESUMEN
OBJECTIVE: The precise pathogenesis or neural correlates underlying levodopa-induced dyskinesia (LID) remains poorly understood. There is growing evidence of the involvement of the cerebellum in Parkinson's disease (PD). The present study evaluated the role of motor cerebellar connectivity in determining vulnerability to LID. METHODS: We enrolled 25 de novo patients with PD who developed LID within 5 years of levodopa treatment, 26 propensity score-matched PD patients who had not developed LID, and 24 age- and sex-matched healthy controls. We performed a comparative analysis of resting-state functional connectivity (FC) between the motor cerebellum and whole brain between the groups. RESULTS: The patients with PD had increased FC bewteen the motor cerebellum and posterior cortical and cerebellar regions, while no gray matter regions had decreased FC with the motor cerebellum compared to the control participant. The patients with PD who were vulnerable to the development of LID had a significantly higher FC between the motor cerebellum lobule VIIIb and the left inferior frontal gyrus than those who were resistant to LID development. The connectivity of the motor cerebellum and left inferior frontal gyrus was negatively correlated with the latency from PD onset to the occurrence of LID. INTERPRETATION: Increased FC between the motor cerebellum and left inferior frontal gyrus in de novo patients with PD could be an important determinant of vulnerability to LID.
Asunto(s)
Antiparkinsonianos/efectos adversos , Cerebelo/patología , Discinesia Inducida por Medicamentos/patología , Levodopa/efectos adversos , Vías Nerviosas/patología , Enfermedad de Parkinson/tratamiento farmacológico , Anciano , Discinesia Inducida por Medicamentos/etiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND AND PURPOSE: Epidemiological studies have suggested the presence of strong correlations among diet, lifestyle, and dementia onset. However, these studies have unfortunately had major limitations due to their inability to fully control the various potential confounders affecting the nutritional status. The purpose of the current study was to determine the nutritional status of participants in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) and to identify clinical risk factors for being at risk of malnutrition or being malnourished. METHODS: Baseline data from 212 participants [119 cognitively unimpaired (CU), 56 with mild cognitive impairment (MCI), and 37 with dementia] included in the KBASE database were analyzed. All participants underwent a comprehensive cognitive test and MRI at baseline. The presence of malnutrition at baseline was measured by the Mini Nutritional Assessment score. We examined the cross-sectional relationships of clinical findings with nutritional status using multiple logistic regression applied to variables for which p<0.2 in the univariate analysis. Differences in cortical thickness according to the nutritional status were also investigated. RESULTS: After adjustment for demographic, nutritional, and neuropsychological factors, participants with dementia had a significantly higher odds ratio (OR) for being at risk of malnutrition or being malnourished than CU participants [OR=5.98, 95% CI=1.20-32.97] whereas participants with MCI did not (OR=0.62, 95% CI=0.20-1.83). Cortical thinning in the at-risk/malnutrition group was observed in the left temporal area. CONCLUSIONS: Dementia was found to be an independent predictor for the risk of malnutrition compared with CU participants. Our findings further suggest that cortical thinning in left temporal regions is related to the nutritional status.