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INTRODUCTION: Pneumopericardium is a dreaded complication in esophageal carcinoma. CASE DESCRIPTION: We report a case of a 62 year old patient with past history of esophageal cancer with pneumopericardium, without hemodynamic compromise. Admission echocardiogram that revealed a pneumopericadium with the presence of the "swirling bubbles" and the "air gap" sign. A small esophagopericardial fistula was postulated as the cause of the pneumopericardium. He underwent esophageal stent placement with almost complete resolution of the pneumopericardium. DISCUSSION: Pneumopericardium is usually a sign of marked clinical deterioration in neoplasia and leads to patients' death few weeks. Here we presented a case, in which a more fortunate and unusual outcome happened. CASE DESCRIPTION: We present a case of a 62 year old patient, with a past history of esophageal cancer with pulmonary metastases undergoing palliative chemotherapy treatment and with two palliative esophageal stents. Other past medical history included active hepatitis B, arterial hypertension and dyslipidaemia. He was an ex smoker of 80 pack-year units.
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Neoplasias Esofágicas , Neumopericardio , Humanos , Masculino , Persona de Mediana Edad , Fístula Esofágica/complicaciones , Neoplasias Esofágicas/complicaciones , Pericardio , Neumopericardio/etiología , Stents/efectos adversosRESUMEN
BACKGROUND: American Academy of Sleep Medicine guidelines suggest that clinical prediction algorithms can be used to screen patients with obstructive sleep apnea (OSA) without replacing polysomnography, the gold standard. OBJECTIVE: We aimed to identify, gather, and analyze existing machine learning approaches that are being used for disease screening in adult patients with suspected OSA. METHODS: We searched the MEDLINE, Scopus, and ISI Web of Knowledge databases to evaluate the validity of different machine learning techniques, with polysomnography as the gold standard outcome measure and used the Prediction Model Risk of Bias Assessment Tool (Kleijnen Systematic Reviews Ltd) to assess risk of bias and applicability of each included study. RESULTS: Our search retrieved 5479 articles, of which 63 (1.15%) articles were included. We found 23 studies performing diagnostic model development alone, 26 with added internal validation, and 14 applying the clinical prediction algorithm to an independent sample (although not all reporting the most common discrimination metrics, sensitivity or specificity). Logistic regression was applied in 35 studies, linear regression in 16, support vector machine in 9, neural networks in 8, decision trees in 6, and Bayesian networks in 4. Random forest, discriminant analysis, classification and regression tree, and nomogram were each performed in 2 studies, whereas Pearson correlation, adaptive neuro-fuzzy inference system, artificial immune recognition system, genetic algorithm, supersparse linear integer models, and k-nearest neighbors algorithm were each performed in 1 study. The best area under the receiver operating curve was 0.98 (0.96-0.99) for age, waist circumference, Epworth Somnolence Scale score, and oxygen saturation as predictors in a logistic regression. CONCLUSIONS: Although high values were obtained, they still lacked external validation results in large cohorts and a standard OSA criteria definition. TRIAL REGISTRATION: PROSPERO CRD42021221339; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=221339.
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Apnea Obstructiva del Sueño , Adulto , Teorema de Bayes , Humanos , Aprendizaje Automático , Redes Neurales de la Computación , Polisomnografía/métodos , Apnea Obstructiva del Sueño/diagnósticoRESUMEN
The Zero Trust concept is being adopted in information technology (IT) deployments, while human users remain to be the main risk for operational technology (OT) deployments. This article proposes to enhance the new Modbus/TCP Security protocol with authentication and authorization functions that guarantee security against intentional unauthorized access. It aims to comply with the principle of never trusting the person who is accessing the network before carrying out a security check. Two functions are tested and used in order to build an access control method that is based on a username and a password for human users with knowledge of industrial automation control systems (IACS), using simple means, low motivation, and few resources. A man-in-the-middle (MITM) component was added in order to intermediate the client and the server communication and to validate these functions. The proposed scenario was implemented using the Node-RED programming platform. The tests implementing the functions and the access control method through the Node-RED software have proven their potential and their applicability.
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Seguridad Computacional , Telemedicina , Humanos , Confidencialidad , Programas InformáticosRESUMEN
Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drug discovery process while saving costs. This is particularly valuable for rare diseases. AI tools have proven their worth in diagnosis, in disease classification and characterization, and ultimately in therapy discovery in rare diseases. The availability of biomarkers and reliable disease models is critical for research and development of new drugs, especially for rare and heterogeneous diseases such as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders' views on AI for therapy discovery in CDG.
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Trastornos Congénitos de Glicosilación , Inteligencia Artificial , Biomarcadores , Trastornos Congénitos de Glicosilación/genética , Reposicionamiento de Medicamentos , Humanos , Enfermedades RarasRESUMEN
Electromagnetic simulations are an important tool for the safety assessment of RF coils. They are a useful resource for MRI RF coil designers, especially when complemented with experimental measurements and testing using physical phantoms. Regular-shaped (spherical/cylindrical) homogeneous phantoms are the MRI standard for RF testing but are somewhat inaccurate when compared with anthropomorphic anatomies, especially at high frequencies. In this work, using a recently developed anthropomorphic heterogeneous human head phantom, studies were performed to analyze the scattering parameters (S-parameters) and the electric and magnetic field distributions using (1) the B1+ field mapping method on a 7 T human MRI scanner and (2) numerical full-wave electromagnetic simulations. All studies used the following: a recently developed six-compartment refillable 3D-printed anthropomorphic head phantom (developed from MRI scans obtained in vivo), where the phantom itself is filled in its entirety with either heterogeneous loading, or homogeneous brain or water loading, in vivo imaging, and a commercial homogeneous spherical water phantom. Our results determined that the calculated S-parameters for all the anthropomorphic head phantom models were comparable to the model that is based on the volunteer (within 17% difference of the reflection coefficient value) but differed for the commercial homogeneous spherical water phantom (within 45% difference). The experimentally measured B1+ field maps of the anthropomorphic heterogeneous and homogeneous brain head phantoms were most comparable to the in vivo measured values. The numerical simulations also show that both the anthropomorphic homogeneous water and brain phantom models were less accurate in terms of electric field intensities/distributions when compared with the segmented in-vivo-based head model and the anthropomorphic heterogeneous head phantom model. The presented data highlights the differences between the physical phantoms/phantom models, and the in vivo measurements/segmented in-vivo-based head model. The results demonstrate the usefulness of 3D-printed anthropomorphic phantoms for RF coil evaluation and testing.
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Campos Electromagnéticos , Imagen por Resonancia Magnética , Fantasmas de Imagen , Electricidad , Cabeza , Humanos , Análisis Numérico Asistido por ComputadorRESUMEN
INTRODUCTION AND OBJECTIVES: Weekend admissions has previously been associated with worse outcomes in conditions requiring specialists. Our study aimed to determine in-hospital outcomes in patients with ascites admitted over the weekends versus weekdays. Time to paracentesis from admission was studied as current guidelines recommend paracentesis within 24h for all patients admitted with worsening ascites or signs and symptoms of sepsis/hepatic encephalopathy (HE). PATIENTS: We analyzed 70 million discharges from the 2005-2014 National Inpatient Sample to include all adult patients admitted non-electively for ascites, spontaneous bacterial peritonitis (SBP), and HE with ascites with cirrhosis as a secondary diagnosis. The outcomes were in-hospital mortality, complication rates, and resource utilization. Odds ratios (OR) and means were adjusted for confounders using multivariate regression analysis models. RESULTS: Out of the total 195,083 ascites/SBP/HE-related hospitalizations, 47,383 (24.2%) occurred on weekends. Weekend group had a higher number of patients on Medicare and had higher comorbidity burden. There was no difference in mortality rate, total complication rates, length of stay or total hospitalization charges between the patients admitted on the weekend or weekdays. However, patients admitted over the weekends were less likely to undergo paracentesis (OR 0.89) and paracentesis within 24h of admission (OR 0.71). The mean time to paracentesis was 2.96 days for weekend admissions vs. 2.73 days for weekday admissions. CONCLUSIONS: We observed a statistically significant "weekend effect" in the duration to undergo paracentesis in patients with ascites/SBP/HE-related hospitalizations. However, it did not affect the patient's length of stay, hospitalization charges, and in-hospital mortality.
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Atención Posterior/tendencias , Ascitis/terapia , Cirrosis Hepática/terapia , Paracentesis/tendencias , Admisión del Paciente/tendencias , Tiempo de Tratamiento/tendencias , Atención Posterior/economía , Ascitis/diagnóstico , Ascitis/economía , Ascitis/mortalidad , Bases de Datos Factuales , Femenino , Precios de Hospital/tendencias , Mortalidad Hospitalaria/tendencias , Humanos , Pacientes Internos , Tiempo de Internación , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/economía , Cirrosis Hepática/mortalidad , Masculino , Persona de Mediana Edad , Paracentesis/efectos adversos , Paracentesis/economía , Paracentesis/mortalidad , Admisión del Paciente/economía , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Tiempo de Tratamiento/economía , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
Defect-related luminescent materials have attracted interest because of their excellent optical properties and are considered as a less expensive and nontoxic alternative to commonly used lanthanide-based optical systems. These materials are fundamentally and technologically important for the next generation of full-color tunable light-emitting diodes as well as in the biomedical field. In this study, we report the preparation of α-silver vanadate (α-AgVO3, AV) decorated by hydroxyapatite (Ca10(PO4)6(OH)2, HA) with intense photoluminescence (PL) emissions at various HA/AV molar ratios (1:1-1:1/32) by a simple route based on chemical precipitation. The well-defined diffraction peaks observed by X-ray diffraction were all indexed to the monoclinic AV and hexagonal HA phases. Analysis of the results obtained by Fourier transform infrared spectroscopy reveals the presence of short-range structural order as deduced by the characteristic vibrational modes assigned to AV and HA systems. Characterization by scanning and transmission electron microscopies confirms the presence of AV and HA micro- and nanorods, respectively. UV-vis spectroscopy renders band gap energies of 5.80 eV for HA and in the range 2.59-2.65 eV for pure AV and HA/AV samples. The PL data reveal the presence of broad-band emission profiles, typical of defect-related optical centers in materials. Depending on the molar ratio, the emission can be completely tunable from the blue to red spectral regions; in addition, pure white color emission was obtained. On the basis of these results, we propose an order-disorder model induced by structural and interface defects to explain the PL emissions in the HA/AV system. Moreover, our results show that HA/AV composites have superior bactericidal activity against Staphylococcus aureus (methicillin-resistant and methicillin-susceptible) and can be used as a novel multifunctional material.
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Antibacterianos/química , Materiales Biocompatibles/química , Durapatita/química , Sustancias Luminiscentes/química , Plata/química , Vanadatos/química , Antibacterianos/farmacología , Materiales Biocompatibles/farmacología , Precipitación Química , Durapatita/farmacología , Humanos , Luminiscencia , Sustancias Luminiscentes/farmacología , Modelos Moleculares , Nanotubos/química , Nanotubos/ultraestructura , Plata/farmacología , Infecciones Estafilocócicas/prevención & control , Staphylococcus aureus/efectos de los fármacos , Vanadatos/farmacologíaRESUMEN
The present study evaluated the efficiency of a structured-bed reactor subjected to recirculation and intermittent aeration (SBRRIA) to promote nitrogen and carbon removal from domestic sewage. The intermittent aeration and the recycling rate of 3 keeps the desired mixing degree inside the SBRRIA. Four different operational conditions were tested by varying the hydraulic retention time (HRT) from 12 to 8â¯h and aerated and non-aerated periods (A/NA) from 2â¯h/1â¯h and 3â¯h/1â¯h. At the THD of 8â¯h and A/NA of 2â¯h/1â¯h there was a decrease in the nitrification process (77.5%) due to the increase of organic matter availability, affecting the total-N removal performance. However, by increasing the aerated period from 2â¯h to 3â¯h, the nitrification efficiency rose to 91.1%, reaching a total-N removal efficiency of 79%. The system reached a maximum total-N loading removed of 0.117â¯kgN.m-3.d-1 by applying an HRT of 8â¯h and an intermittent aeration cycle of 3â¯h, aerated and 1â¯h non-aerated. The simultaneous nitrification and denitrification (SND) process was related to a complex interplay among microorganisms affiliated mostly to Acidovorax sp., Comamonas sp., Dechloromonas sp., Hydrogenophaga sp., Mycobacterium sp., Rhodobacter sp., and Steroidobacter sp.
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Reactores Biológicos , Carbono/aislamiento & purificación , Nitrificación , Desnitrificación , Nitrógeno , Aguas del AlcantarilladoRESUMEN
The effect of the fungicide pyrimethanil (0.7 mg L(−1)) on biofilm development and alder leaf litter decomposition in aquatic ecosystems was assessed in outdoor lentic mesocosms immediately and 274 days after pyrimethanil application. Pyrimethanil decreased ergosterol concentrations (an indicator of fungal biomass) and the abundance and richness of the macroinvertebrate community associated with decomposing leaves. However, because neither fungi nor macroinvertebrates were main factors contributing to decomposition in this particular system, organic matter processing rates were not affected. After 274 days, pyrimethanil concentration in the water column was ≤0.004 mg L(−1) but richness, biomass and composition of the invertebrate community associated with decomposing leaf-litter still showed the effect. The comparison of ergosterol (a molecule existing on both algae and fungal cell membranes), with chlorophyll (an indicator of algal biomass) associated with biofilm suggests that pyrimethanil may decrease fungal biomass and alter the relative abundance of algae and fungi on biofilm developing in control- and treated-mesocosms.
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Fenómenos Fisiológicos Bacterianos/efectos de los fármacos , Biopelículas/efectos de los fármacos , Fungicidas Industriales/metabolismo , Compuestos Orgánicos/metabolismo , Pirimidinas/metabolismo , Contaminantes Químicos del Agua/metabolismo , Relación Dosis-Respuesta a Droga , Estanques/química , Estanques/microbiología , Portugal , Estaciones del AñoRESUMEN
Pentachlorophenol (PCP) is globally dispersed and contamination of soil with this biocide adversely affects its functional biodiversity, particularly of fungi - key colonizers. Their functional role as a community is poorly understood, although a few pathways have been already elucidated in pure cultures. This constitutes here our main challenge - elucidate how fungi influence the pollutant mitigation processes in forest soils. Circumstantial evidence exists that cork oak forests in N. W. Tunisia - economically critical managed forests are likely to be contaminated with PCP, but the scientific evidence has previously been lacking. Our data illustrate significant forest contamination through the detection of undefined active sources of PCP. By solving the taxonomic diversity and the PCP-derived metabolomes of both the cultivable fungi and the fungal community, we demonstrate here that most strains (predominantly penicillia) participate in the pollutant biotic degradation. They form an array of degradation intermediates and by-products, including several hydroquinone, resorcinol and catechol derivatives, either chlorinated or not. The degradation pathway of the fungal community includes uncharacterized derivatives, e.g. tetrachloroguaiacol isomers. Our study highlights fungi key role in the mineralization and short lifetime of PCP in forest soils and provide novel tools to monitor its degradation in other fungi dominated food webs.
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Bosques , Hongos/metabolismo , Pentaclorofenol/metabolismo , Quercus/metabolismo , Microbiología del Suelo , Contaminantes del Suelo/metabolismo , Biodegradación Ambiental , Biodiversidad , Contaminación Ambiental , Hongos/aislamiento & purificación , Suelo/química , TúnezRESUMEN
Aspergilli play major roles in the natural turnover of elements, especially through the decomposition of plant litter, but the end catabolism of lignin aromatic hydrocarbons remains largely unresolved. The 3-oxoadipate pathway of their degradation combines the catechol and the protocatechuate branches, each using a set of specific genes. However, annotation for most of these genes is lacking or attributed to poorly- or un-characterised families. Aspergillus nidulans can utilise as sole carbon/energy source either benzoate or salicylate (upstream aromatic metabolites of the protocatechuate and the catechol branches, respectively). Using this cultivation strategy and combined analyses of comparative proteomics, gene mining, gene expression and characterisation of particular gene-replacement mutants, we precisely assigned most of the steps of the 3-oxoadipate pathway to specific genes in this fungus. Our findings disclose the genetically encoded potential of saprophytic Ascomycota fungi to utilise this pathway and provide means to untie associated regulatory networks, which are vital to heightening their ecological significance.
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Adipatos/metabolismo , Aspergillus nidulans/genética , Aspergillus nidulans/metabolismo , Aspergillus nidulans/enzimología , Ácido Benzoico/metabolismo , Catecoles/metabolismo , Enzimas/genética , Técnicas de Sustitución del Gen , Genes Fúngicos , Hidroxibenzoatos/metabolismo , Lignina/metabolismo , Redes y Vías Metabólicas/genética , Proteómica , Salicilatos/metabolismoRESUMEN
Death of retinal neural cells, namely retinal ganglion cells (RGCs), is a characteristic of several retinal neurodegenerative diseases. Although the role of adenosine A3 receptor (A3R) in neuroprotection is controversial, A3R activation has been reported to afford protection against several brain insults, with few studies in the retina. In vitro models (retinal neural and organotypic cultures) and animal models [ischemia-reperfusion (I-R) and partial optic nerve transection (pONT)] were used to study the neuroprotective properties of A3R activation against retinal neurodegeneration. The A3R selective agonist (2-Cl-IB-MECA, 1 µM) prevented apoptosis (TUNEL(+)-cells) induced by kainate and cyclothiazide (KA + CTZ) in retinal neural cultures (86.5 ± 7.4 and 37.2 ± 6.1 TUNEL(+)-cells/field, in KA + CTZ and KA + CTZ + 2-Cl-IB-MECA, respectively). In retinal organotypic cultures, 2-Cl-IB-MECA attenuated NMDA-induced cell death, assessed by TUNEL (17.3 ± 2.3 and 8.3 ± 1.2 TUNEL(+)-cells/mm(2) in NMDA and NMDA+2-Cl-IB-MECA, respectively) and PI incorporation (ratio DIV4/DIV2 3.3 ± 0.3 and 1.3 ± 0.1 in NMDA and NMDA+2-Cl-IB-MECA, respectively) assays. Intravitreal 2-Cl-IB-MECA administration afforded protection against I-R injury decreasing the number of TUNEL(+) cells by 72%, and increased RGC survival by 57%. Also, intravitreal administration of 2-Cl-IB-MECA inhibited apoptosis (from 449.4 ± 37.8 to 207.6 ± 48.9 annexin-V(+)-cells) and RGC loss (from 1.2 ± 0.6 to 8.1 ± 1.7 cells/mm) induced by pONT. This study demonstrates that 2-Cl-IB-MECA is neuroprotective to the retina, both in vitro and in vivo. Activation of A3R may have great potential in the management of retinal neurodegenerative diseases characterized by RGC death, as glaucoma and diabetic retinopathy, and ischemic diseases.
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Neuroprotección/fisiología , Receptor de Adenosina A3/metabolismo , Degeneración Retiniana/prevención & control , Neuronas Retinianas/metabolismo , Adenosina/análogos & derivados , Adenosina/farmacología , Agonistas del Receptor de Adenosina A3/farmacología , Antagonistas del Receptor de Adenosina A3/farmacología , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Supervivencia Celular , Modelos Animales de Enfermedad , Agonistas de Aminoácidos Excitadores/toxicidad , Técnica del Anticuerpo Fluorescente Indirecta , Etiquetado Corte-Fin in Situ , Inyecciones Intravítreas , Masculino , N-Metilaspartato/toxicidad , Traumatismos del Nervio Óptico/metabolismo , Técnicas de Cultivo de Órganos , Ratas , Ratas Wistar , Retina/efectos de los fármacos , Retina/patología , Degeneración Retiniana/metabolismoRESUMEN
Diabetic retinopathy is a leading cause of vision loss and blindness. Disruption of axonal transport is associated with many neurodegenerative diseases and might also play a role in diabetes-associated disorders affecting nervous system. We investigated the impact of type 1 diabetes (2 and 8 weeks duration) on KIF1A, KIF5B and dynein motor proteins in the retina. Additionally, since hyperglycemia is considered the main trigger of diabetic complications, we investigated whether prolonged exposure to elevated glucose could affect the content and distribution of motor proteins in retinal cultures. The immunoreactivity of motor proteins was evaluated by immunohistochemistry in retinal sections and by immunoblotting in total retinal extracts from streptozotocin-induced diabetic and age-matched control animals. Primary retinal cultures were exposed to high glucose (30 mM) or mannitol (osmotic control; 24.5 mM plus 5.5 mM glucose), for seven days. Diabetes decreased the content of KIF1A at 8 weeks of diabetes as well as KIF1A immunoreactivity in the majority of retinal layers, except for the photoreceptor and outer nuclear layer. Changes in KIF5B immunoreactivity were also detected by immunohistochemistry in the retina at 8 weeks of diabetes, being increased at the photoreceptor and outer nuclear layer, and decreased in the ganglion cell layer. Regarding dynein immunoreactivity there was an increase in the ganglion cell layer after 8 weeks of diabetes. No changes were detected in retinal cultures. These alterations suggest that axonal transport may be impaired under diabetes, which might contribute to early signs of neural dysfunction in the retina of diabetic patients and animal models.
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Transporte Axonal/fisiología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Dineínas/metabolismo , Cinesinas/metabolismo , Neuronas Retinianas/metabolismo , Animales , Western Blotting , Células Cultivadas , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patología , Dineínas/genética , Técnica del Anticuerpo Fluorescente Indirecta , Glucosa/farmacología , Hiperglucemia/metabolismo , Cinesinas/genética , Masculino , Manitol/farmacología , Microscopía Confocal , ARN Mensajero/genética , Ratas , Ratas Wistar , Neuronas Retinianas/efectos de los fármacos , Neuronas Retinianas/patologíaRESUMEN
Saprophytic fungi are able to catabolize many plant-derived aromatics, including, for example, gallate. The catabolism of gallate in fungi is assumed to depend on the five main central pathways, i.e., of the central intermediates' catechol, protocatechuate, hydroxyquinol, homogentisate and gentisate, but a definitive demonstration is lacking. To shed light on this process, we analysed the transcriptional reprogramming of the growth of Aspergillus terreus on gallate compared with acetate as the control condition. Surprisingly, the results revealed that the five main central pathways did not exhibit significant positive regulation. Instead, an in-depth analysis identified four highly expressed and upregulated genes that are part of a conserved gene cluster found in numerous species of fungi, though not in Aspergilli. The cluster comprises a monooxygenase gene and a fumarylacetoacetate hydrolase-like gene, which are recognized as key components of catabolic pathways responsible for aromatic compound degradation. The other two genes encode proteins with no reported enzymatic activities. Through functional analyses of gene deletion mutants in Aspergillus nidulans, the conserved short protein with no known domains could be linked to the conversion of the novel metabolite 5-hydroxydienelatone, whereas the DUF3500 gene likely encodes a ring-cleavage enzyme for 1,2,3,5-tetrahydroxybenzene. These significant findings establish the existence of a new 1,2,3,5-tetrahydroxybenzene central pathway for the catabolism of gallate and related compounds (e.g. 2,4,6-trihydroxybenzoate) in numerous fungi where this catabolic gene cluster was observed.
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Hongos , Gentisatos , Fenoles , Hongos/genéticaRESUMEN
Aspergilli comprise a diversity of species that have been extensively studied due to their catabolic diversity, biotechnological and ecological value, and pathogenicity. An impressive level of structural and functional conservation has been shown for aspergilli, regardless of many (yet) cryptic genomic elements. We have hypothesized the existence of conserved genes responsive to stress in aspergilli. To test the hypothesis of such conserved stress regulators in aspergilli, a straightforward computational strategy integrating well-established bioinformatic tools was used as the starting point. Specifically, five transcriptome-based datasets on exposure to organic compounds were used, covering three distinct Aspergillus species. Among the identified up-regulated genes, only one gene showed the same response in all conditions, AN9181. This gene encodes a protein containing a phenylcoumaran benzylic ether reductase-like domain and a Nitrogen metabolite repressor regulator domain (NmrA). Deletion of this gene caused significant phenotypic alterations compared to that of the parental strain across diverse conditions. Specifically, the deletion of AN9181 raised the mutant's metabolic activity in different nitrogen sources. The acquired data supports that AN9181 acts by repressing (slowing down) A. nidulans growth when exposed to aromatic compounds in a concentration dependent manner. The same phenotype was observed for amphotericin B. Finally, AN9181 underwent differential upregulation under oxidative stress conditions. Collectively, the data suggest that AN9181, herein assigned as NmrB (Nitrogen Metabolite Repression Regulator B), builds up the genetic machinery of perception of oxidative stress by negatively regulating growth under such conditions.
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The development of innovative non-invasive neuroimaging methods and biomarkers is critical for studying brain disease. Imaging of cerebrospinal fluid (CSF) pulsatility may inform the brain fluid dynamics involved in clearance of cerebral metabolic waste. In this work, we developed a methodology to characterize the frequency and spatial localization of whole brain CSF pulsations in humans. Using 7 Tesla (T) human magnetic resonance imaging (MRI) and ultrafast echo-planar imaging (EPI), in-vivo images were obtained to capture pulsations of the CSF signal. Physiological data were simultaneously collected and compared with the 7 T MR data. The primary components of signal pulsations were identified using spectral analysis, with the most evident frequency bands identified around 0.3, 1.2, and 2.4 Hz. These pulsations were mapped spatially and temporally onto the MR image domain and temporally onto the physiological measures of electrocardiogram and respiration. We identified peaks in CSF pulsations that were distinct from peaks in grey matter and white matter regions. This methodology may provide novel in vivo biomarkers of disrupted brain fluid dynamics.
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Long-chain polyunsaturated n-3 fatty acids (n-3 LCPUFAs) have hypolipidemic effects and modulate intermediary metabolism to prevent or reverse insulin resistance in a way that is not completely elucidated. Here, effects of these fatty acids on the lipid profile, phosphoenolpyruvate carboxykinase (PEPCK) activity, lipid synthesis from glucose in epididymal adipose tissue (Ep-AT) and liver were investigated. Male rats were fed a high-sucrose diet (SU diet), containing either sunflower oil or a mixture of sunflower and fish oil (SU-FO diet), and the control group was fed a standard diet. After 13 weeks, liver, adipose tissue and blood were harvested and analysed. The dietary n-3 LCPUFAs prevented sucrose-induced increase in adiposity and serum free fat acids, serum and hepatic triacylglycerol and insulin levels. Furthermore, these n-3 LCPUFAs decreased lipid synthesis from glucose and increased PEPCK activity in the Ep-AT of rats fed the SU-FO diet compared to those fed the SU diet, besides reducing lipid synthesis from glucose in hepatic tissue. Thus, the inclusion of n-3 LCPUFAs in the diet may be beneficial for the prevention or attenuation of dyslipidemia and insulin resistance, and for reducing the risk of related chronic diseases.
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Tejido Adiposo/metabolismo , Sacarosa en la Dieta/administración & dosificación , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-3/farmacología , Glucosa/metabolismo , Lípidos/biosíntesis , Fosfoenolpiruvato Carboxiquinasa (ATP)/metabolismo , Tejido Adiposo/efectos de los fármacos , Animales , Sacarosa en la Dieta/farmacología , Suplementos Dietéticos , Activación Enzimática/efectos de los fármacos , Glucosa/química , Masculino , Ratas , Ratas WistarRESUMEN
We reported previously that intrauterine asphyxia acutely affects the rat hippocampus. For this reason, the early effects of this injury were studied in the cerebral cortex, immediately after hysterectomy (acute condition) or following a recovery period at normoxia (recovery condition). Lactacidemia and glycemia were determined, as well as glycogen levels in the muscle, liver and cortex. Cortical tissue was also used to assay the ATP levels and glutamate uptake. Asphyxiated pups exhibited bluish coloring, loss of movement, sporadic gasping and hypertonia. However, the appearance of the controls and asphyxiated pups was similar at the end of the recovery period. Lactacidemia and glycemia were significantly increased by asphyxia in both the acute and recovery conditions. Concerning muscle and hepatic glycogen, the control group showed significantly higher levels than the asphyxic group in the acute condition and when compared with groups of the recovery period. In the recovery condition, the control and asphyxic groups showed similar glycogen levels. However, in the cortex, the control groups showed significantly higher glycogen levels than the asphyxic group, in both the acute and recovery conditions. In the cortical tissue, asphyxia reduced ATP levels by 70 % in the acute condition, but these levels increased significantly in asphyxic pups after the recovery period. Asphyxia did not affect glutamate transport in the cortex of both groups. Our results suggest that the cortex uses different energy resources to restore ATP after an asphyxia episode followed by a reperfusion period. This strategy could sustain the activity of essential energy-dependent mechanisms.
Asunto(s)
Animales Recién Nacidos/metabolismo , Asfixia/metabolismo , Corteza Cerebral/metabolismo , Ácido 3-Hidroxibutírico/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Glucemia/análisis , Femenino , Ácido Láctico/sangre , Ratas , Ratas WistarRESUMEN
The present study assesses the effects of starvation and refeeding on 1-[(14)C]-methyl aminoisobutyric acid ((14)C-MeAIB) uptake, (14)C-total lipids, (14)CO(2) production from (14)C-glycine, (14)C-protein synthesis from (14)C-leucine and Na(+)-K(+)-ATPase activity in jaw muscle of Neohelice granulata previously maintained on a carbohydrate-rich (HC) or high-protein (HP) diet. In N. granulata the metabolic adjustments during starvation and refeeding use different pathways according to the composition of the diet previously offered to the crabs. During starvation, (14)CO(2) production from (14)C-glycine, and (14)C-protein synthesis from (14)C-leucine were reduced in HC-fed crabs. In crabs maintained on the HP or HC diet, (14)C-total lipid synthesis increased after 15 days of starvation. In crabs fed HP diet, (14)C-MeAIB uptake and Na(+)-K(+)-ATPase activity decreased in refeeding state. In crabs refeeding HC diet, (14)C-MeAIB uptake and (14)CO(2) production decreased during the refeeding. In contrast, the (14)C-protein synthesis increased after 120h of refeeding. In both dietary groups, (14)C-total lipid synthesis increased during refeeding. Changes in the carbon amino acid flux between different metabolic pathways in muscle are among the strategies used by this crab to face starvation and refeeding. Protein or carbohydrate levels in the diet administered to this crab modulate the carbon flux between the different metabolic pathways.