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The final stages of female gamete maturation occur in the virtual absence of transcription, with gene expression driven by a program of selective unmasking, translation, and degradation of maternal mRNAs. Here we demonstrate that the timing of Ccnb1 mRNA translation in mouse oocytes is dependent on the presence of transcripts with different 3' untranslated regions (UTRs). This 3' UTR heterogeneity directs distinct temporal patterns of translational activation or repression. Inclusion or exclusion of cis-acting elements is responsible for these divergent regulations. Our findings reveal an additional layer of translation control through alternative polyadenylation usage required to fine-tune the timing of meiosis progression.
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Ciclina B1/genética , Regulación del Desarrollo de la Expresión Génica , Meiosis/genética , Oocitos/crecimiento & desarrollo , ARN Mensajero/genética , Regiones no Traducidas 3'/genética , Animales , Ciclina B1/metabolismo , Femenino , Ratones , Ratones Endogámicos C57BL , Oocitos/citología , Poliadenilación , ARN Mensajero/metabolismoRESUMEN
Pregnancy loss (PL) in lactating dairy cows disrupts reproductive and productive efficiency. We evaluated the expression of interferon-stimulated genes (ISG) in blood leukocytes, vaginal and cervical epithelial cells, luteolysis-related genes, progesterone, and pregnancy-associated glycoprotein (PAG) profiles in lactating dairy cows (n = 86) to gain insight about PL. Expression of ISG on d17, d19, and d21 was greater in cows that maintained the pregnancy (P33) compared to nonpregnant with no PL (NP). Greater ISG differences between groups were observed in the cervix (96.7-fold) than vagina (31.0-fold), and least in blood leukocytes (5.6-fold). Based on individual profiles of ISG and PAG, PL was determined to occur either before (~13%) or after (~25%) d22. For cows with PL before d22, ISG expression was similar on d17 but by d21 was lower and OXTR was greater than P33 cows and similar to NP; timing of luteolysis was similar compared to NP cows suggesting embryonic failure to promote luteal maintenance and to attach to the endometrium (no increase in PAG). For cows with PL after d22, ISG expression was similar to P33 cows on d17, d19, and d21 and luteolysis, when it occurred, was later than NP cows; delayed increase in PAG suggested later or inadequate embryonic attachment. In conclusion, PL before d22 occurred due to embryonic demise/failure to signal for luteal maintenance, as reflected in reduced ISG expression by d21. Alternatively, embryos with PL between d22 and 33 adequately signaled for luteal maintenance (ISG) but had delayed/inadequate embryonic attachment and/or inappropriate luteolysis causing PL.
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Aborto Espontáneo , Interferones , Embarazo , Femenino , Humanos , Bovinos , Animales , Lactancia , Inseminación Artificial/veterinaria , Progesterona , GlicoproteínasRESUMEN
In September 2023, the UK Health Security Agency identified cases of Salmonella Saintpaul distributed across England, Scotland, and Wales, all with very low genetic diversity. Additional cases were identified in Portugal following an alert raised by the United Kingdom. Ninety-eight cases with a similar genetic sequence were identified, 93 in the United Kingdom and 5 in Portugal, of which 46% were aged under 10 years. Cases formed a phylogenetic cluster with a maximum distance of six single nucleotide polymorphisms (SNPs) and average of less than one SNP between isolates. An outbreak investigation was undertaken, including a case-control study. Among the 25 UK cases included in this study, 13 reported blood in stool and 5 were hospitalized. One hundred controls were recruited via a market research panel using frequency matching for age. Multivariable logistic regression analysis of food exposures in cases and controls identified a strong association with cantaloupe consumption (adjusted odds ratio: 14.22; 95% confidence interval: 2.83-71.43; p-value: 0.001). This outbreak, together with other recent national and international incidents, points to an increase in identifications of large outbreaks of Salmonella linked to melon consumption. We recommend detailed questioning and triangulation of information sources to delineate consumption of specific fruit varieties during Salmonella outbreaks.
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Brotes de Enfermedades , Intoxicación Alimentaria por Salmonella , Humanos , Portugal/epidemiología , Masculino , Adulto , Femenino , Reino Unido/epidemiología , Persona de Mediana Edad , Niño , Adolescente , Estudios de Casos y Controles , Adulto Joven , Anciano , Preescolar , Intoxicación Alimentaria por Salmonella/epidemiología , Intoxicación Alimentaria por Salmonella/microbiología , Cucumis melo/microbiología , Salmonella/genética , Salmonella/aislamiento & purificación , Salmonella/clasificación , Lactante , Anciano de 80 o más Años , FilogeniaRESUMEN
AIMS: Climate change is endangering olive groves. Farmers are adapting by exploring new varieties of olive trees and examining the role of microbiomes in plant health.The main objectives of this work were to determine the primary factors that influence the microbiome of olive trees and to analyze the connection between the rhizosphere and endosphere compartments. METHODS AND RESULTS: The rhizosphere and xylem sap microbiomes of two olive tree varieties were characterized by next-generation 16S rRNA amplicon sequencing, and soil descriptors were analyzed. Bacterial communities in the rhizosphere of olive trees were more diverse than those found in the xylem sap. Pseudomonadota, Actinobacteriota, Acidobacteriota, and Bacillota were the dominant phyla in both compartments. At the genus level, only very few taxa were shared between soil and sap bacterial communities. CONCLUSIONS: The composition of the bacteriome was more affected by the plant compartment than by the olive cultivar or soil properties, and a direct route from the rhizosphere to the endosphere could not be confirmed. The large number of plant growth-promoting bacteria found in both compartments provides promising prospects for improving agricultural outcomes through microbiome engineering.
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Bacterias , Microbiota , Olea , ARN Ribosómico 16S , Rizosfera , Microbiología del Suelo , Xilema , Olea/microbiología , ARN Ribosómico 16S/genética , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Xilema/microbiología , Raíces de Plantas/microbiología , Suelo/químicaRESUMEN
BACKGROUND: Physical fitness is a health marker in youth and is associated with current and future health. OBJECTIVE: Present the healthy fitness zone (HFZ) prevalence and age-specific fitness profile of young people from seven European countries. METHODS: This study used data from the European Fitness Monitoring System project. The sample comprised 4965 (51.4% boys) youths aged 9 to 18 years. Fitness data were collected by physical education teachers using field-based tests. Raw data from the fitness tests were used to calculate the prevalence and 95% confidence intervals (CI) of participants in the HFZ. RESULTS: The overall prevalence of boys and girls in the HFZ for all tests was 16.6% (95% CI = 14.7, 18.1) and 14.9% (95% CI = 13.2, 16.6), respectively. Boys have a mainly positive HFZ profiles, except for the 9-year-olds in the sit and reach (z-score difference = -1.20) and the 20 m run for boys 13-18-year-olds (z-score difference range: -0.09 to -0.01). Girls have worse HFZ profiles than boys, being out of the HFZ in several tests. Furthermore, a decreasing trend in z-score difference from the HFZ with age was observed in VO2 peak for boys and girls and sit and reach for girls. Notwithstanding, several country-related, sex and age differences were observed. CONCLUSIONS: Boys presented mostly healthy age-specific fitness profiles in several fitness tests and ages. These differences should be considered when promoting youth's health through physical activity and fitness, as different fitness levels may require different approaches to implementing health-enhancing physical activity policies.
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Ejercicio Físico , Aptitud Física , Masculino , Femenino , Adolescente , Humanos , Prevalencia , Prueba de Esfuerzo , Factores de Edad , Índice de Masa CorporalRESUMEN
The aim of this study was to describe the goals, activities, and methods of EUMOVE project in developing a set of resources targeting both primary and secondary schools that allow the entire educational community to promote healthy lifestyles (HL). The EUMOVE project is an Erasmus+ program based in the Creating Active Schools (CAS) framework. The project lasted 3 years and was developed by 14 academic and non-governmental institutions from Spain, Portugal, France, Italy, and the UK. EUMOVE was divided into three phases. In the first phase, several work packages were carried out aimed to ensure the coordination/management of the project activities. In the second phase, seven educational resources strengthened by rigorous scientific research were developed to promote HL from schools. During the last phase, all the resources were disseminated through scientific seminars, workshops with families and teachers, and the online promotion by the non-governmental institutions of each country. The EUMOVE project developed and promoted a smartphone APP, video/activity repository of physically active lessons, active break virtual platform, learning units, and parent/teachers/school-leaders' guidelines to promote physical activity, active commuting, active school playgrounds, healthy diet, and sleep habits. To our knowledge, EUMOVE is the first European project to provide a set of practical tools based on scientific evidence to help schools or future school-wide interventions implement a paradigm shift based on the CAS framework for the promotion of HL. Future research will need to investigate the implementation, effectiveness, and scalability of this proposal.
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Negative symptoms reflect a currently much-untreated loss of normal functioning and are frequently found in psychotic disorders. We present the first translation of the Brief Negative Symptom Scale (BNSS) to European Portuguese and evaluate its validity in a sample of Portuguese male patients with a psychotic spectrum disorder. The Portuguese BNSS showed excellent internal consistency, high convergent validity (i.e., strong correlation with the PANSS negative factor), and high discriminant validity (i.e., a lack of association with the PANSS positive factor). In sum, the present European Portuguese BNSS has shown to be reliable, thus extending this instrument's clinical availability worldwide.
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Esquizofrenia , Humanos , Masculino , Esquizofrenia/diagnóstico , Escalas de Valoración Psiquiátrica , Portugal , Psicometría , Reproducibilidad de los ResultadosRESUMEN
Our objective was to determine the effect of a 200-µg dose of GnRH 25 d after previous artificial insemination (AI) in a Resynch-25 resynchronization program on ovulatory response, circulating progesterone (P4) concentrations before and after treatment, and pregnancy per AI (P/AI) compared with a 100-µg dose in lactating Holstein cows. Experimental d 0 was considered the day of the previous AI. Lactating dairy cows (n = 3,240) with an average of 126 d in milk (DIM) and between 1 and 6 services were randomly assigned to receive 100 µg or 200 µg of GnRH on d 25 (GnRH25). On d 32 after AI, cows diagnosed nonpregnant with the presence of a corpus luteum (CL) detected by ultrasound (n = 1,249) received PGF2α treatments on d 32 and 33, followed by a GnRH 32 h later and AI 16 h after this last GnRH. Blood samples were collected on d 25, 32, and 34 to evaluate serum P4 concentrations. Transrectal ultrasonographic examination was performed on d 25 and 27 to assess ovulatory response to GnRH25. Cows were checked for pregnancy on d 32, 46, and 88 after AI. The larger dose of GnRH increased the overall proportion of cows that ovulated to the GnRH25 (25.0% for the 100-µg dose vs. 32.5% for the 200-µg dose). However, when cows were evaluated separately according to the pregnancy status on d 32 after AI, we found no treatment effect within cows pregnant and nonpregnant. Even though treatment increased the proportion of cows with serum P4 ≤0.42 ng/mL at the last GnRH treatment (G2; 86.2% for the 100-µg dose vs. 93.0% for the 200-µg dose), it did not affect P/AI on d 32, 46, and 88. Furthermore, a greater proportion of cows without a functional CL at GnRH25 had circulating P4 concentrations ≥1.00 ng/mL on d 32 and lower than 0.42 ng/mL on G2. These cows also had a greater P/AI on d 32, 46, and 88. In summary, the larger dose of GnRH on d 25 after AI did not increase the ovulatory response in nonpregnant cows and P/AI on d 32, 46, and 88 after AI after the Resynch-25 program. Additionally, nonpregnant cows without a functional CL at GnRH25 were better synchronized after the Resynch-25 protocol and had greater P/AI on d 32, 46, and 88 after timed-AI.
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Sincronización del Estro , Lactancia , Animales , Bovinos , Femenino , Embarazo , Dinoprost/farmacología , Sincronización del Estro/métodos , Fertilidad/fisiología , Hormona Liberadora de Gonadotropina/farmacología , Inseminación Artificial/veterinaria , Inseminación Artificial/métodos , Lactancia/fisiología , ProgesteronaRESUMEN
An outbreak of hepatitis A is ongoing in Portugal, with 71 confirmed cases from 7 October 2023 to 24 April 2024. Most cases are male, aged 18-44 years, with many identifying as men who have sex with men (MSM) and reported as suspected sexual transmission. Phylogenetic analysis identified the subgenotype IA, VRD 521-2016 strain, last observed in an MSM-associated multi-country outbreak in 2016 to 2018. We wish to alert colleagues in other countries to investigate potential similar spread.
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Brotes de Enfermedades , Genotipo , Hepatitis A , Homosexualidad Masculina , Filogenia , Humanos , Masculino , Portugal/epidemiología , Hepatitis A/epidemiología , Hepatitis A/transmisión , Homosexualidad Masculina/estadística & datos numéricos , Adulto , Adolescente , Adulto Joven , Virus de la Hepatitis A/genética , Virus de la Hepatitis A/aislamiento & purificación , Virus de la Hepatitis A/clasificación , Persona de Mediana Edad , Conducta Sexual , Femenino , Trazado de ContactoRESUMEN
BackgroundLeptospirosis is a zoonotic disease caused by bacteria of the genus Leptospira. Humans are infected by exposure to animal urine or urine-contaminated environments. Although disease incidence is lower in Europe compared with tropical regions, there have been reports of an increase in leptospirosis cases since the 2000s in some European countries.AimWe aimed to describe the epidemiology of reported cases of leptospirosis in the European Union/European Economic Area (EU/EEA) during 2010-2021 and to identify potential changes in epidemiological patterns.MethodsWe ran a descriptive analysis of leptospirosis cases reported by EU/EEA countries to the European Centre for Disease Prevention and Control with disease during 2010-2021. We also analysed trends at EU/EEA and national level.ResultsDuring 2010-2021, 23 countries reported 12,180 confirmed leptospirosis cases corresponding to a mean annual notification rate of 0.24 cases per 100,000 population. Five countries (France, Germany, the Netherlands, Portugal and Romania) accounted for 79% of all reported cases. The highest notification rate was observed in Slovenia with 0.82 cases per 100,000 population. Overall, the notification rate increased by 5.0% per year from 2010 to 2021 (95% CI: 1.2-8.8%), although trends differed across countries.ConclusionThe notification rate of leptospirosis at EU/EEA level increased during 2010-2021 despite including the first 2 years of the COVID-19 pandemic and associated changes in population behaviours. Studies at (sub)national level would help broaden the understanding of differences at country-level and specificities in terms of exposure to Leptospira, as well as biases in diagnosis and reporting.
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Leptospira , Leptospirosis , Humanos , Pandemias , Europa (Continente)/epidemiología , Unión Europea , Rumanía , Leptospirosis/diagnóstico , Leptospirosis/epidemiologíaRESUMEN
Currently, the market for wearable devices is expanding, with a growing trend towards the use of these devices for continuous-monitoring applications. Among these, real-time posture monitoring and assessment stands out as a crucial application given the rising prevalence of conditions like forward head posture (FHP). This paper proposes a wearable device that combines the acquisition of electromyographic signals from the cervical region with inertial data from inertial measurement units (IMUs) to assess the occurrence of FHP. To improve electronics integration and wearability, e-textiles are explored for the development of surface electrodes and conductive tracks that connect the different electronic modules. Tensile strength and abrasion tests of 22 samples consisting of textile electrodes and conductive tracks produced with three fiber types (two from Shieldex and one from Imbut) were conducted. Imbut's Elitex fiber outperformed Shieldex's fibers in both tests. The developed surface electromyography (sEMG) acquisition hardware and textile electrodes were also tested and benchmarked against an electromyography (EMG) gold standard in dynamic and isometric conditions, with results showing slightly better root mean square error (RMSE) values (for 4 × 2 textile electrodes (10.02%) in comparison to commercial Ag/AgCl electrodes (11.11%). The posture monitoring module was also validated in terms of joint angle estimation and presented an overall error of 4.77° for a controlled angular velocity of 40°/s as benchmarked against a UR10 robotic arm.
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Electromiografía , Postura , Textiles , Dispositivos Electrónicos Vestibles , Electromiografía/métodos , Humanos , Postura/fisiología , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , ElectrodosRESUMEN
The current article reports the investigation of three new Ni(II) complexes with ONS-donor dithiocarbazate ligands: [Ni(L1)PPh3] (1), [Ni(L2)PPh3] (2), and [Ni(L2)Py] (3). Single-crystal X-ray analyses revealed mononuclear complexes with a distorted square planar geometry and the metal centers coordinated with a doubly deprotonated dithiocarbazate ligand and coligand pyridine or triphenylphosphine. The non-covalent interactions were investigated by the Hirshfeld surface and the results revealed that the strongest interactions were πâ â â π stacking interactions and non-classical hydrogen bonds C-H···H and C-H···N. Physicochemical and spectroscopic methods indicate the same structures in the solid state and solution. The toxicity effects of the free ligands and Ni(II) complexes were tested on the human breast cancer cell line MCF-7 and non-malignant breast epithelial cell line MCF-10A. The half-maximal inhibitory concentration (IC50) values, indicating that the compounds were potent in inhibiting cell growth, were obtained for both cell lines at three distinct time points. While inhibitory effects were evident in both malignant and non-malignant cells, all three complexes demonstrated lower IC50 values for malignant breast cell lines than their non-malignant counterparts, suggesting a stronger impact on cancerous cell lines. Furthermore, molecular docking studies were performed showing the complex (2) as a promising candidate for further therapeutic exploration.
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Antineoplásicos , Complejos de Coordinación , Simulación del Acoplamiento Molecular , Níquel , Humanos , Níquel/química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Ligandos , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/síntesis química , Línea Celular Tumoral , Cristalografía por Rayos X , Células MCF-7 , Estructura Molecular , Proliferación Celular/efectos de los fármacos , Diseño de FármacosRESUMEN
Objective: Assessing effectiveness of circular (CM) and linear (LM) scrub methods using 3 different combinations of chlorhexidine in surgical field antisepsis in cats. Animals and procedure: Surgical field antisepsis was applied with 2 scrub methods (CM and LM) and 3 different chlorhexidine combinations (A1, A2, and A3) in 51 female cats undergoing ovariectomy. Sterile swabs collected from the surgical field pre- and post-antisepsis were inoculated in the laboratory and colony-forming units (CFU/mL) were quantified. Results: Following the application of antisepsis, the number of positive samples decreased in all groups (P < 0.05) when using both CM and LM, except for CM in the A1 group (P = 0.063). The CFU/mL counts also decreased after antisepsis with both CM and LM in all groups (P < 0.05). A high reduction in CFU/mL counts was observed after antisepsis with both CM and LM in all groups, but no significant differences were observed between the 2 scrub methods (P > 0.05). Conclusion and clinical relevance: Surgical field antisepsis in cats with CM and LM scrub methods, using 2% chlorhexidine combined with 70% ethyl or 70% isopropyl alcohol, or 1% chlorhexidine combined with 70% ethyl alcohol, can effectively reduce the bacterial load on the skin.
Efficacité de deux méthodes de désinfection avec différentes combinaisons de chlorhexidine pour l'antisepsie du champ opératoire chez le chat. Objectif: Évaluation de l'efficacité des méthodes de désinfection par mouvements circulaires (CM) et linéaires (LM) utilisant 3 combinaisons différentes de chlorhexidine dans l'antisepsie du champ opératoire chez le chat. Animaux et procédure: Une antisepsie chirurgicale sur le terrain a été appliquée avec 2 méthodes de désinfection (CM et LM) et 3 combinaisons différentes de chlorhexidine (A1, A2 et A3) chez 51 chattes subissant une ovariectomie. Des écouvillons stériles prélevés sur le champ opératoire avant et après l'antisepsie ont été inoculés en laboratoire et les unités formant des colonies (UFC/mL) ont été quantifiées. Résultats: À la suite de l'application de l'antisepsie, le nombre d'échantillons positifs a diminué dans tous les groupes (P < 0,05) lors de l'utilisation à la fois de CM et de LM, à l'exception du CM dans le groupe A1 (P = 0,063). Le nombre d'UFC/mL a également diminué après antisepsie avec CM et LM dans tous les groupes (P < 0,05). Une forte réduction du nombre d'UFC/mL a été observée après antisepsie avec CM et LM dans tous les groupes, mais aucune différence significative n'a été observée entre les 2 méthodes de désinfection (P > 0,05). Conclusion et pertinence clinique: L'antisepsie chirurgicale sur le terrain chez les chats avec les méthodes de désinfection CM et LM, utilisant 2 % de chlorhexidine combinée à 70 % d'alcool éthylique ou 70 % d'alcool isopropylique, ou 1 % de chlorhexidine combinée à 70 % d'alcool éthylique, peut réduire efficacement la charge bactérienne sur la peau.(Traduit par Dr Serge Messier).
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Antiinfecciosos Locales , Clorhexidina , Infección de la Herida Quirúrgica , Animales , Clorhexidina/administración & dosificación , Gatos , Femenino , Antiinfecciosos Locales/administración & dosificación , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/veterinaria , Ovariectomía/veterinaria , Antisepsia/métodosRESUMEN
(1) Background: Recent digital workflows are being developed for full-arch rehabilitations supported by implants with immediate function. The purpose of this case series is to describe a new digital workflow for the All-on-4 concept. (2) Methods: The patients were rehabilitated using the All-on-4 concept with a digital workflow including computerized tomography scanning, intra-oral scanning, and CAD-CAM production of the temporary prosthesis, with the 3D printing of stackable guides (base guide, implant guide, and prosthetic guide). The passive fit of the prostheses and the time to perform the rehabilitations were evaluated. (3) Results: The digital workflow allowed for predictable bone reduction, the insertion of implants with immediate function, and the connection of an implant-supported prosthesis with immediate loading. The time registered to perform the full-arch rehabilitations (implant insertion, abutment connection, prosthesis connection) was below 2 hours and 30 min. No passive fit issues were noted. (4) Conclusions: within the limitation of this case series, the digital workflow applied to the All-on-4 concept using stackable base-, implant-, and prosthetic guides constitutes a potential alternative with decreased time for the procedure without prejudice of the outcome.
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Flujo de Trabajo , Humanos , Femenino , Masculino , Persona de Mediana Edad , Diseño Asistido por Computadora , Anciano , Prótesis Dental de Soporte Implantado/métodos , Impresión Tridimensional , Tomografía Computarizada por Rayos X/métodos , Boca Edéntula/rehabilitaciónRESUMEN
Functional MRI (fMRI) with 1 H-MRS was combined on the hippocampus and visual cortex of animal models of obesity (high-fat diet, HFD) and type 2 diabetes (T2D) to identify the involved mechanisms and temporal evolution of neurometabolic changes in these disorders that could serve as potentially reliable clinical biomarkers. HFD rats presented elevated levels of N-acetylaspartylglutamate (NAAG) (p = 0.0365 vs. standard diet, SD) and glutathione (GSH) (p = 0.0494 vs. SD) in the hippocampus. NAAG and GSH levels in this structure proved to be correlated (r = 0.4652, p = 0.0336). This mechanism was not observed in diabetic rats. Combining MRS and fMRI-evaluated blood-oxygen-level-dependent (BOLD) response, elevated taurine (p = 0.0326 vs. HFD) and GABA type A receptor (GABAA R) (p = 0.0211 vs. SD and p = 0.0153 vs. HFD) were observed in the visual cortex of only diabetic rats, counteracting the elevated BOLD response and suggesting an adaptative mechanism against hyperexcitability observed in the primary visual cortex (V1) (p = 0.0226 vs. SD). BOLD amplitude was correlated with the glutamate levels (r = 0.4491; p = 0.0316). Therefore, here we found evidence for several biological dichotomies regarding excitotoxicity and neuroprotection in different brain regions, identifying putative markers of their different susceptibility and response to the metabolic and vascular insults of obesity and diabetes.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Neuroquímica , Corteza Visual , Ratas , Animales , Neuroprotección , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Hipocampo/diagnóstico por imagen , Hipocampo/metabolismo , Corteza Visual/diagnóstico por imagen , Corteza Visual/metabolismo , Ácido Glutámico/metabolismo , Modelos Animales , Obesidad/diagnóstico por imagen , Obesidad/metabolismo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Axon ensheathment is fundamental for fast impulse conduction and the normal physiological functioning of the nervous system. Defects in axonal insulation lead to debilitating conditions, but, despite its importance, the molecular players responsible are poorly defined. Here, we identify RalA GTPase as a key player in axon ensheathment in Drosophila larval peripheral nerves. We demonstrate through genetic analysis that RalA action through the exocyst complex is required in wrapping glial cells to regulate their growth and development. We suggest that the RalA-exocyst pathway controls the targeting of secretory vesicles for membrane growth or for the secretion of a wrapping glia-derived factor that itself regulates growth. In summary, our findings provide a new molecular understanding of the process by which axons are ensheathed in vivo, a process that is crucial for normal neuronal function.
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Axones/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Unión al GTP Monoméricas/metabolismo , Vaina de Mielina/metabolismo , Nervios Periféricos/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Animales , Animales Modificados Genéticamente , Fasciculación Axonal/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Larva/metabolismo , Locomoción/genética , Proteínas de Unión al GTP Monoméricas/genética , Mutación , Neuroglía/metabolismo , Interferencia de ARNRESUMEN
BACKGROUND: The consumption of high-caloric diets strongly contributes to the development of non-communicable diseases (NCDs), including cardiovascular disease, the leading cause of mortality worldwide. Exercise (along with diet intervention) is one of the primary non-pharmacological approaches to promote a healthier lifestyle and counteract the rampant prevalence of NCDs. The present study evaluated the effects of exercise cessation after a short period training on the cardiac metabolic and mitochondrial function of female rats. METHODS: Seven-week-old female Sprague-Dawley rats were fed a control or a high-fat, high-sugar (HFHS) diet and, after 7 weeks, the animals were kept on a sedentary lifestyle or submitted to endurance exercise for 3 weeks (6 days per week, 20-60 min/day). The cardiac samples were analysed 8 weeks after exercise cessation. RESULTS: The consumption of the HFHS diet triggered impaired glucose tolerance, whereas the HFHS diet and physical exercise resulted in different responses in plasma adiponectin and leptin levels. Cardiac mitochondrial respiration efficiency was decreased by the HFHS diet consumption, which led to reduced ATP and increased NAD(P)H mitochondrial levels, which remained prevented by exercise 8 weeks after cessation. Exercise training-induced cardiac adaptations in redox balance, namely increased relative expression of Nrf2 and downstream antioxidant enzymes persist after an eight-week exercise cessation period. CONCLUSIONS: Endurance exercise modulated cardiac redox balance and mitochondrial efficiency in female rats fed a HFHS diet. These findings suggest that exercise may elicit cardiac adaptations crucial for its role as a non-pharmacological intervention for individuals at risk of developing NCDs.
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Maternal obesity (MO) is rising worldwide, affecting half of all gestations, constituting a possible risk-factor for some pregnancy-associated liver diseases (PALD) and hepatic diseases. PALD occur in approximately 3% of pregnancies and are characterized by maternal hepatic oxidative stress (OS) and mitochondrial dysfunction. Maternal hepatic disease increases maternal and fetal morbidity and mortality. Understanding the role of MO on liver function and pathophysiology could be crucial for better understanding the altered pathways leading to PALD and liver disease, possibly paving the way to prevention and adequate management of disease. We investigated specific hepatic metabolic alterations in mitochondria and oxidative stress during MO at late-gestation. Maternal hepatic tissue was collected at 90% gestation in Control and MO ewes (fed 150% of recommended nutrition starting 60 days before conception). Maternal hepatic redox state, mitochondrial respiratory chain (MRC), and OS markers were investigated. MO decreased MRC complex-II activity and its subunits SDHA and SDHB protein expression, increased complex-I and complex-IV activities despite reduced complex-IV subunit mtCO1 protein expression, and increased ATP synthase ATP5A subunit. Hepatic MO-metabolic remodeling was characterized by decreased adenine nucleotide translocator 1 and 2 (ANT-1/2) and voltage-dependent anion channel (VDAC) protein expression and protein kinase A (PKA) activity (P<0.01), and augmented NAD+/NADH ratio due to reduced NADH levels (P<0.01). MO showed an altered redox state with increased OS, increased lipid peroxidation (P<0.01), decreased GSH/GSSG ratio (P=0.005), increased superoxide dismutase (P=0.03) and decreased catalase (P=0.03) antioxidant enzymatic activities, lower catalase, glutathione peroxidase (GPX)-4 and glutathione reductase protein expression (P<0.05), and increased GPX-1 abundance (P=0.03). MO-related hepatic changes were more evident in the right lobe, corroborated by the integrative data analysis. Hepatic tissue from obese pregnant ewes showed alterations in the redox state, consistent with OS and MRC and metabolism remodeling. These are hallmarks of PALD and hepatic disease, supporting MO as a risk-factor and highlighting OS and mitochondrial dysfunction as mechanisms responsible for liver disease predisposition.
Asunto(s)
Hepatopatías , NAD , Humanos , Femenino , Embarazo , Animales , Ovinos , Catalasa/metabolismo , NAD/metabolismo , Hígado/metabolismo , Estrés Oxidativo , Obesidad/metabolismo , Antioxidantes/metabolismo , Hepatopatías/metabolismo , Superóxido Dismutasa/metabolismo , Glutatión/metabolismoRESUMEN
In vitro cell-based characterization methods of nanoparticles are generally static and require the use of secondary analysis techniques and labeling agents. In this study, bare niosomes and chitosan-coated niosomes (chitosomes) and their interactions with intestinal cells are studied under dynamic conditions and without fluorescent probes, using surface plasmon resonance (SPR)-based cell sensing. Niosomes and chitosomes were synthesized by using Tween 20 and cholesterol in a 15 mM:15 mM ratio and then characterized by dynamic light scattering (DLS). DLS analysis demonstrated that bare niosomes had average sizes of â¼125 nm, polydispersity index (PDI) below 0.2, and a negative zeta (ζ)-potential of -35.6 mV. In turn, chitosomes had increased sizes up to â¼180 nm, with a PDI of 0.2-0.3 and a highly positive ζ-potential of +57.9 mV. The viability of HT29-MTX, Caco-2, and Caco-2/HT29-MTX cocultured cells showed that both niosomes and chitosomes are cytocompatible up to concentrations of 31.6 µg/mL for at least 240 min. SPR analysis demonstrated that chitosomes interact more efficiently with HT29-MTX, Caco-2, and Caco-2/HT29-MTX cocultures compared to bare niosomes. The resulting SPR measurements were further supported by confocal microscopy and flow cytometry studies, which demonstrated that this method is a useful complementary or even alternative tool to directly characterize the interactions between niosomes and in vitro cell models in label-free and real-time conditions.
Asunto(s)
Quitosano , Liposomas , Humanos , Células CACO-2 , IntestinosRESUMEN
The electronic properties of SO2 at the surface of a water cluster were investigated by employing a combination of Born-Oppenheimer molecular dynamics and electron propagator theory (EPT). In our work, we utilized a revised version of the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional, which incorporates empirical corrections for dispersion interactions in line with a recent study of the air-water interface conducted by Ohto et al. [J. Phys. Chem. Lett. 10(17), 4914-4919 (2019)]. Polarization effects induce a significant broadening of the electron binding energy distribution, as predicted by EPT. This broadening can result in a substantial increase in electron affinity, impacting the chemical reactivity of SO2 at the air-water interface, a topic of significant and recent research interest. We discuss the relationship between electron binding energies (EBEs) and the specific connections of SO2 to water. The results indicate that configurations involving an OSâ¯H bond tend to yield higher electron affinities compared to complex formation through Sâ¯OW bonds. Surprisingly, SO2 molecules not bound to water molecules according to a specific criterion may also exhibit higher electron affinities. This feature can be explained by the role played by the polarization field from water molecules. Our best estimate for the HOMO-LUMO (H-L) gap of SO2 at the surface of a water cluster is 11.6 eV. Very similar H-L gaps are predicted for isolated and micro-solvated SO2. Fukui functions for the gas phase, and the micro-solvated SO2-H2O complex supports the view that the LUMO is predominantly localized on the SO2 moiety.