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Type-IV glandular trichomes, which only occur in the juvenile developmental phase of the cultivated tomato (Solanum lycopersicum), produce acylsugars that broadly protect against arthropod herbivory. Previously, we introgressed the capacity to retain type-IV trichomes in the adult phase from the wild tomato, Solanum galapagense, into the cultivated species cv. Micro-Tom (MT). The resulting MT-Galapagos enhanced trichome (MT-Get) introgression line contained 5 loci associated with enhancing the density of type-IV trichomes in adult plants. We genetically dissected MT-Get and obtained a subline containing only the locus on Chromosome 2 (MT-Get02). This genotype displayed about half the density of type-IV trichomes compared to the wild progenitor. However, when we stacked the gain-of-function allele of WOOLLY, which encodes a homeodomain leucine zipper IV transcription factor, Get02/Wo exhibited double the number of type-IV trichomes compared to S. galapagense. This discovery corroborates previous reports positioning WOOLLY as a master regulator of trichome development. Acylsugar levels in Get02/Wo were comparable to the wild progenitor, although the composition of acylsugar types differed, especially regarding fewer types with medium-length acyl chains. Agronomical parameters of Get02/Wo, including yield, were comparable to MT. Pest resistance assays showed enhanced protection against silverleaf whitefly (Bemisia tabaci), tobacco hornworm (Manduca sexta), and the fungus Septoria lycopersici. However, resistance levels did not reach those of the wild progenitor, suggesting the specificity of acylsugar types in the pest resistance mechanism. Our findings in trichome-mediated resistance advance the development of robust, naturally resistant tomato varieties, harnessing the potential of natural genetic variation. Moreover, by manipulating only 2 loci, we achieved exceptional results for a highly complex, polygenic trait, such as herbivory resistance in tomato.
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Solanum lycopersicum , Tricomas , Tricomas/genética , Solanum lycopersicum/genética , Solanum lycopersicum/parasitología , Animales , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mutación/genética , Herbivoria , Herencia Multifactorial , Manduca/fisiología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/parasitologíaRESUMEN
Learning and behavior activate cue-specific patterns of sparsely distributed cells and synapses called ensembles that undergo memory-encoding engram alterations. While Fos is often used to label selectively activated cell bodies and identify neuronal ensembles, there is no comparable endogenous marker to label activated synapses and identify synaptic ensembles. For the purpose of identifying candidate synaptic activity markers, we optimized a flow cytometry of synaptoneurosome (FCS) procedure for assessing protein alterations in activated synapses from male and female rats. After injecting yellow fluorescent protein (YFP)-expressing adeno-associated virus into medial prefrontal cortex (mPFC) to label terminals in nucleus accumbens (NAc) of rats, we injected 20 mg/kg cocaine in a novel context (cocaine+novelty) to activate synapses, and prepared NAc synaptoneurosomes 0-60 min following injections. For FCS, we used commercially available antibodies to label presynaptic and postsynaptic markers synaptophysin and PSD-95 as well as candidate markers of synaptic activity [activity-regulated cytoskeleton protein (Arc), CaMKII and phospho-CaMKII, ribosomal protein S6 (S6) and phospho-S6, and calcineurin and phospho-calcineurin] in YFP-labeled synaptoneurosomes. Cocaine+novelty increased the percentage of S6-positive synaptoneurosomes at 5-60 min and calcineurin-positive synaptoneurosomes at 5-10 min. Electron microscopy verified that S6 and calcineurin levels in synaptoneurosomes were increased 10 min after cocaine+novelty. Pretreatment with the anesthetic chloral hydrate blocked cocaine+novelty-induced S6 and calcineurin increases in synaptoneurosomes, and novel context exposure alone (without cocaine) increased S6, both of which indicate that these increases were due to neural activity per se. Overall, FCS can be used to study protein alterations in activated synapses coming from specifically labeled mPFC projections to NAc.SIGNIFICANCE STATEMENT Memories are formed during learning and are stored in the brain by long-lasting molecular and cellular alterations called engrams formed within specific patterns of cue-activated neurons called neuronal ensembles. While Fos has been used to identify activated ensemble neurons and the engrams within them, we have not had a similar marker for activated synapses that can be used to identify synaptic engrams. Here we developed a procedure for high-throughput in-line analysis of flow cytometry of synaptoneurosome (FCS) and found that ribosomal S6 protein and calcineurin were increased in activated mPFC-NAc synapses. FCS can be used to study protein alterations in activated synapses within specifically labeled circuits.
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Calcineurina , Cocaína , Femenino , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Núcleo Accumbens/fisiología , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Citometría de Flujo , Sinapsis , Corteza Prefrontal/fisiología , Cocaína/farmacologíaRESUMEN
KEY MESSAGE: Genome-wide association study of color spaces across the four cultivated Capsicum spp. revealed a shared set of genes influencing fruit color, suggesting mechanisms and pathways across Capsicum species are conserved during the speciation. Notably, Cytochrome P450 of the carotenoid pathway, MYB transcription factor, and pentatricopeptide repeat-containing protein are the major genes responsible for fruit color variation across the Capsicum species. Peppers (Capsicum spp.) rank among the most widely consumed spices globally. Fruit color, serving as a determinant for use in food colorants and cosmeceuticals and an indicator of nutritional contents, significantly influences market quality and price. Cultivated Capsicum species display extensive phenotypic diversity, especially in fruit coloration. Our study leveraged the genetic variance within four Capsicum species (Capsicum baccatum, Capsicum chinense, Capsicum frutescens, and Capsicum annuum) to elucidate the genetic mechanisms driving color variation in peppers and related Solanaceae species. We analyzed color metrics and chromatic attributes (Red, Green, Blue, L*, a*, b*, Luminosity, Hue, and Chroma) on samples cultivated over six years (2015-2021). We resolved genomic regions associated with fruit color diversity through the sets of SNPs obtained from Genotyping by Sequencing (GBS) and genome-wide association study (GWAS) with a Multi-Locus Mixed Linear Model (MLMM). Significant SNPs with FDR correction were identified, within the Cytochrome P450, MYB-related genes, Pentatricopeptide repeat proteins, and ABC transporter family were the most common among the four species, indicating comparative evolution of fruit colors. We further validated the role of a pentatricopeptide repeat-containing protein (Chr01:31,205,460) and a cytochrome P450 enzyme (Chr08:45,351,919) via competitive allele-specific PCR (KASP) genotyping. Our findings advance the understanding of the genetic underpinnings of Capsicum fruit coloration, with developed KASP assays holding potential for applications in crop breeding and aligning with consumer preferences. This study provides a cornerstone for future research into exploiting Capsicum's diverse fruit color variation.
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Capsicum , Frutas , Fenotipo , Pigmentación , Polimorfismo de Nucleótido Simple , Capsicum/genética , Capsicum/crecimiento & desarrollo , Frutas/genética , Frutas/crecimiento & desarrollo , Pigmentación/genética , Color , Genotipo , Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Sistema Enzimático del Citocromo P-450/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Variación GenéticaRESUMEN
Realistic simulation models for interventional radiology procedures are limited, including for placement of double-J stents (DJS). Utilizing a porcine kidney and empty saline bag (bladder), an ex-vivo model aiming to improve operator's knowledge and confidence in performing a DJS procedure was developed. Six faculty and fourteen trainees successfully operated on the model. Mean results for faculty vs. trainees are as follows: 2.2 ± 1.5 vs 2.4 ± 1.9 puncture attempts to access collecting system (p = 0.78), 14.5 ± 4.8 vs. 15.1 ± 6.0 minutes for insertion time (p = 0.84), 7.3 ± 2.8 vs. 10.3 ± 2.6 minutes for exchange time (p = 0.04), 8.48 ± 2.0 vs. 8.01 ± 2.6 minutes for fluoroscopy time (p = 0.70), and 5.7 ± 1.6 vs. 5.4 ± 2.0 mGy for absorbed air kerma (p = 0.77). Self-assessed knowledge and confidence with DJS placement increased for all participants following model use.
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PURPOSE: To utilize a novel ex vivo perfused human renal model and quantify microwave ablation (MWA) size differences in renal tissue when combining MWA with transarterial embolization (TAE). MATERIALS AND METHODS: Human kidneys (n = 5) declined for transplantation were obtained and connected to a fluoroscopy-compatible ex vivo perfusion system. Two ablations-1 standard MWA and 1 TAE-MWA-were performed in each kidney for 2 minutes at 100 W using a MWA system (Solero Angiodynamics). MWA alone was performed in the upper pole. In the lower pole, MWA was performed after TAE with 40-90 µm radiopaque microspheres to achieve angiographic stasis. Ablation zones of coagulative necrosis were sectioned along the long axis and segmented for maximal short-axis diameter (SAD) and long-axis diameter (LAD) measurements. RESULTS: A total of 10 ablations (5 MWAs and 5 TAE-MWAs) were performed in 5 human kidneys. TAE-MWA resulted in significantly increased SAD, LAD, volume, and sphericity compared with standard MWA ± SD, with mean measurements as follows (5 standard MWAs ± SD vs 5 TAE-MWAs ± SD, 2-tailed t-test): (a) SAD, 1.8 cm (SD ± 0.1) versus 2.5 cm (SD ± 0.1) (P < .001); (b) LAD, 2.9 cm (SD ± 0.3) versus 3.2 cm (SD ± 0.1) (P = .039); (c) volume, 5.0 mL (SD ± 0.5) versus 11.0 mL (SD ± 0.7) (P < .001); and (d) sphericity, 0.4 (SD ± 0.2) versus 0.6 (SD ± 0.1) (P = .049). Histology demonstrated no differences in TAE-MWA other than concentrated microspheres. CONCLUSIONS: This ex vivo human kidney perfusion model confirmed that combined MWA-TAE significantly increased ablation size and spherical shape compared with MWA alone.
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PURPOSE: To develop a reproducible in vitro model simulating central venous catheter (CVC) exchange with high potential for air embolization and test the hypothesis that a closed catheter clamp over hydrophilic guide wire exchange technique will significantly reduce the volume of air introduced during CVC exchange. MATERIALS AND METHODS: The model consisted of a 16-F valved sheath, 240-mL container, and pressure transducer submerged in water in a 1,200-mL suction canister system. Continuous wall suction was applied to the canister to maintain negative pressure at -7 mm Hg or -11 mm Hg. Each trial consisted of 0.035-inch hydrophilic guide wire introduction, over-the-wire catheter exchange, and wire removal following clinical protocol. A total of 256 trials were performed, 128 trials at each pressure with the catheter clamp open (n = 64) or closed (n = 64) around the hydrophilic guide wire. RESULTS: There was a statistically significant lower volume of air introduced with closed clamp over-the-wire exchanges than with open clamp exchanges at both pressures (2-tailed t-test, P < .001). At -7 mm Hg, a mean of 48.0 mL (SD ± 9.3) of air was introduced with open clamp and 20.6 mL (SD ± 4.7) of air was introduced with closed clamp. At -11 mm Hg, 97.8 mL (SD ± 11.9) of air was introduced with open clamp and 37.8 mL (SD ± 6.3) of air was introduced with closed clamp. CONCLUSIONS: This study demonstrated the use of a reproducible in vitro model mimicking conditions causing air embolism during CVC exchange. Results showed that CVC exchange using closed catheter clamp over hydrophilic guide wire exchange technique significantly reduced the volume of air introduced per exchange.
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Cateterismo Venoso Central , Catéteres Venosos Centrales , Embolia Aérea , Humanos , Catéteres Venosos Centrales/efectos adversos , Embolia Aérea/etiología , Embolia Aérea/prevención & control , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/métodosRESUMEN
Bile leaks arise from various causes such as trauma, complications after hepatobiliary surgery, and intrahepatic malignancies or their associated liver-directed treatments. Bile leaks can result in significant morbidity and mortality. Delayed diagnosis is not uncommon due to nonspecific manifestations; therefore, a high clinical suspicion is needed. A multidisciplinary approach for treatment of biliary leaks with prompt referral to tertiary care centers with experienced hepatobiliary surgeons, advanced endoscopists, and interventional radiologists is needed to address these challenging complications. Management of biliary leaks can range from conservative management to open surgical repair. Minimally invasive procedures play a crucial role in biliary leak treatment, and the interventional radiologist can help guide appropriate management on the basis of a clear understanding of the pathophysiology of biliary leaks and a current knowledge of the armamentarium of treatment options. In most cases, a simple diversion of bile to decompress the biliary system may prove effective. However, persistent and high-output biliary leaks require delineation of the source with tailored treatment options to control the leak. This may be done by additional diversions, occluding the source, reestablishing connections, or using a combination of therapies to bridge to more definitive surgical interventions. The authors describe the different treatment options and emphasize the role of interventional radiology. ©RSNA, 2024.
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Complicaciones Posoperatorias , Humanos , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/terapia , Enfermedades de las Vías Biliares/diagnóstico por imagen , Enfermedades de las Vías Biliares/terapia , Fuga Anastomótica/diagnóstico por imagen , Fuga Anastomótica/terapia , Grupo de Atención al PacienteRESUMEN
BACKGROUND AND AIMS: Social determinants of health (SDH) are critical in health outcomes. More insight is needed on the correlation between SDH and metabolic syndrome (MetS) in the aging population. This study assessed the association between SDH and MetS scores among older adults in Colombia. METHODS AND RESULTS: This cross-sectional country-wide study includes a sample of 4085 adults aged ≥60 from the SABE Colombia Survey. MetS measurements were central obesity, hyperglycemia or diabetes, hypertriglyceridemia, arterial hypertension, and low HDL cholesterol (MetS score 0-5). SDH includes four levels: 1- general socioeconomic and environmental conditions; 2-social and community networks; 3- individual lifestyle; and 4-constitutional factors. In multivariate linear regression analysis, the SDH factors with greater effect sizes, calculated by Eta Squared, predicting higher MetS mean scores were women followed by low education, no alcohol intake, urban origin, and residing in unsafe neighborhoods. Two interactions: men, but not women, have lower MetS in safe neighborhoods compared to unsafe, and men, but not women, have lower MetS when having low education (0-5 years) compared to high (≥6). CONCLUSION: Gender, education, alcohol intake, and origin have the greatest effect sizes on MetS. Education level and neighborhood safety modified the relationship between gender and MetS. Low-educated men or those residing in safe neighborhoods have lower MetS. Neighborhood environments and educational differences influencing MetS should be considered in future studies.
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Síndrome Metabólico , Determinantes Sociales de la Salud , Humanos , Colombia/epidemiología , Síndrome Metabólico/epidemiología , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/sangre , Masculino , Femenino , Anciano , Estudios Transversales , Persona de Mediana Edad , Factores de Edad , Factores Sexuales , Medición de Riesgo , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/efectos adversos , Escolaridad , Factores Socioeconómicos , Factores de Riesgo , Anciano de 80 o más Años , Encuestas Epidemiológicas , Factores de Riesgo CardiometabólicoRESUMEN
Curcumin, a polyphenol derived from Curcuma longa, used as a dietary spice, has garnered attention for its therapeutic potential, including antioxidant, anti-inflammatory, and antimicrobial properties. Despite its known benefits, the precise mechanisms underlying curcumin's effects on consumers remain unclear. To address this gap, we employed the genetic model Drosophila melanogaster and leveraged two omics tools-transcriptomics and metabolomics. Our investigation revealed alterations in 1043 genes and 73 metabolites upon supplementing curcumin into the diet. Notably, we observed genetic modulation in pathways related to antioxidants, carbohydrates, and lipids, as well as genes associated with gustatory perception and reproductive processes. Metabolites implicated in carbohydrate metabolism, amino acid biosynthesis, and biomarkers linked to the prevention of neurodegenerative diseases such as schizophrenia, Alzheimer's, and aging were also identified. The study highlighted a strong correlation between the curcumin diet, antioxidant mechanisms, and amino acid metabolism. Conversely, a lower correlation was observed between carbohydrate metabolism and cholesterol biosynthesis. This research highlights the impact of curcumin on the diet, influencing perception, fertility, and molecular wellness. Furthermore, it directs future studies toward a more focused exploration of the specific effects of curcumin consumption.
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Curcumina , Drosophila melanogaster , Metaboloma , Transcriptoma , Animales , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Curcumina/farmacología , Curcumina/administración & dosificación , Metaboloma/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/metabolismo , Dieta , Metabolómica/métodosRESUMEN
BACKGROUND: Extracellular vesicles (EVs), including small EVs (sEVs) such as exosomes, exhibit great potential for the diagnosis and treatment of brain disorders, representing a valuable tool for precision medicine. The latter demands high-quality human biospecimens, especially in complex disorders in which pathological and specimen heterogeneity, as well as diverse individual clinical profile, often complicate the development of precision therapeutic schemes and patient-tailored treatments. Thus, the collection and characterization of physiologically relevant sEVs are of the utmost importance. However, standard brain EV isolation approaches rely on tissue dissociation, which can contaminate EV fractions with intracellular vesicles. METHODS: Based on multiscale analytical platforms such as cryo-EM, label-free proteomics, advanced flow cytometry, and ExoView analyses, we compared and characterized the EV fraction isolated with this novel method with a classical digestion-based EV isolation procedure. Moreover, EV biogenesis was pharmacologically manipulated with either GW4869 or picrotoxin to assess the validity of the spontaneous-release method, while the injection of labelled-EVs into the mouse brain further supported the integrity of the isolated vesicles. RESULTS: We hereby present an efficient purification method that captures a sEV-enriched population spontaneously released by mouse and human brain tissue. In addition, we tested the significance of the release method under conditions where biogenesis/secretion of sEVs was pharmacologically manipulated, as well as under animals' exposure to chronic stress, a clinically relevant precipitant of brain pathologies, such as depression and Alzheimer's disease. Our findings show that the released method monitors the drug-evoked inhibition or enhancement of sEVs secretion while chronic stress induces the secretion of brain exosomes accompanied by memory loss and mood deficits suggesting a potential role of sEVs in the brain response to stress and related stress-driven brain pathology. CONCLUSIONS: Overall, the spontaneous release method of sEV yield may contribute to the characterization and biomarker profile of physiologically relevant brain-derived sEVs in brain function and pathology. Video Abstract.
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Enfermedad de Alzheimer , Exosomas , Vesículas Extracelulares , Humanos , Animales , Ratones , Encéfalo , BiomarcadoresRESUMEN
PURPOSE: Identifying actionable oncogenic mutations have changed the therapeutic landscape in different types of tumors. This study investigated the utility of comprehensive genomic profiling (CGP), a hybrid capture-based next-generation sequencing (NGS) assay, in clinical practice in a developing country. METHODS: In this retrospective cohort study, CGP was performed on clinical samples from patients with different solid tumors recruited between December 2016 and November 2020, using hybrid capture-based genomic profiling, at the individual treating physicians' request in the clinical care for therapy decisions. Kaplan-Meier survival curves were estimated to characterize the time-to-event variables. RESULTS: Patients median age was 61 years (range: 14-87 years), and 64.7% were female. The most common histological diagnosis was lung primary tumors, with 90 patients corresponding to 52.9% of the samples (95% CI 45.4-60.4%). Actionable mutations with FDA-approved medications for specific alterations correspondent to tumoral histology were identified in 58 cases (46.4%), whereas other alterations were detected in 47 different samples (37.6%). The median overall survival was 15.5 months (95% CI 11.7 months-NR). Patients who were subjected to genomic evaluation at diagnosis reached a median overall survival of 18.3 months (95% CI 14.9 months-NR) compared to 14.1 months (95% CI 11.1 months-NR) in patients who obtained genomic evaluation after tumor progression and during standard treatment (P = .7). CONCLUSION: CGP of different types of tumors identifies clinically relevant genomic alterations that have benefited from targeted therapy and improve cancer care in a developing country to guide personalized treatment to beneficial outcomes of cancer patients.
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Países en Desarrollo , Neoplasias Pulmonares , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Neoplasias Pulmonares/patología , Mutación , Genómica , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
INTRODUCTION: The Memory Complaint Scale (MCS-15) is a 15-item instrument to explore frequent forgetfulness in daily life in people with possible cognitive impairment. However, knowledge about its psychometric performance is limited. OBJECTIVE: The objective of this study was to know the dimensionality and internal consistency of the MCS-15 in Colombian older adults. METHODS: A probabilistic sample of 1,957 older adults from the general Colombian population was taken, aged between 60 and 98 years (mean = 71.0 ± 7.9), and 62.2% were women. Internal consistency (Cronbach's alpha and McDonald's omega) and dimensionality (exploratory and confirmatory factor analysis) were calculated for the original and ten-item versions. RESULTS: The 15-item version showed Cronbach's alpha and McDonald's omega of 0.91, and one dimension accounted for 45.3% of the variance. A version of ten items showed Cronbach's alpha and McDonald's omega of 0.89 and a single factor that explained 50.9% of the variance with better indicators in the confirmatory factor analysis. Convergence with the shortened Mini-Mental State Examination was rs = 0.43 (p < 0.001), and the Montreal Cognitive Assessment test was rs = 0.38 (p < 0.001). The nomological validity with the geriatric depression scale was rs = 0.44 (p < 0.001), and women scored higher than men (p < 0.001). CONCLUSIONS: The MCS-15 shows high internal consistency with poor dimensionality. However, a ten-item version shows high internal consistency and a clear one-dimensional structure. More research is needed: testing the performance against a structured interview for major cognitive impairment.
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Disfunción Cognitiva , Masculino , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Psicometría , Colombia , Reproducibilidad de los Resultados , Análisis Factorial , Disfunción Cognitiva/diagnóstico , Encuestas y CuestionariosRESUMEN
This study hypothesized that an ex vivo renal perfusion model can create smaller microwave ablation (MWA) measurements during perfused states compared with nonperfused states across multiple device settings. Nine bovine kidneys, a fluoroscopic compatible perfusion model, and a commercially-available clinical MWA system were used to perform 72 ablations (36 perfused and 36 nonperfused) at 9 different device settings. Comparing perfused and nonperfused ablations at each device setting, significant differences in volume existed for 6 of 9 settings (P < .05). Collapsed across time settings, the ablation volumes by power were the following (perfused and nonperfused, P value): 60 W, 2.3 cm3 ± 1.0 and 7.2 cm3 ± 2.7, P < .001; 100 W, 5.4 cm3 ± 2.1 and 11.5 cm3 ± 5.6, P < .01; and 140 W, 11.2 cm3 ± 3.7 and 18.7 cm3 ± 6.3, P < .01. Applied power correlated with ablation volume: perfused, 0.021 cm3/W and R = 0.462, P = .004, and nonperfused, 0.029 cm3/W and R = 0.565, P < .001. These results support that an ex vivo perfused organ system can evaluate MWA systems and demonstrate heat sink perfusion effects of decreased ablation size.
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Técnicas de Ablación , Ablación por Catéter , Ablación por Radiofrecuencia , Humanos , Animales , Bovinos , Hígado/cirugía , Microondas/uso terapéutico , Perfusión/métodos , Ablación por Catéter/métodos , Riñón/cirugíaRESUMEN
Metabolic syndrome (MetS) is a rapidly increasing health concern during midlife and is an emerging risk factor for the development of neurodegenerative diseases, such as Alzheimer's disease (AD). While angiotensin receptor blockers (ARB) are widely used for MetS-associated hypertension and kidney disease, its therapeutic potential in the brain during MetS are not well-described. Here, we tested whether treatment with ARB could alleviate the brain pathology and inflammation associated with MetS using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. Here, we report that chronic ARB treatment with olmesartan (10 mg/kg/day by oral gavage for 6 weeks) partially but significantly ameliorated accumulation of oxidized and ubiquitinated proteins, astrogliosis and transformation to neurotoxic astrocytes in the brain of old OLETF rats, which otherwise exhibit the progression of these pathological hallmarks associated with MetS. Additionally, olmesartan treatment restored claudin-5 and ZO-1, markers of the structural integrity of the blood-brain barrier as well as synaptic protein PSD-95, which were otherwise decreased in old OLETF rats, particularly in the hippocampus, a critical region in cognition, memory and AD. These data demonstrate that the progression of MetS in OLETF rats is associated with deterioration of various aspects of neuronal integrity that may manifest neurodegenerative conditions and that overactivation of angiotensin receptor directly or indirectly contributes to these detriments. Thus, olmesartan treatment may slow or delay the onset of degenerative process in the brain and subsequent neurological disorders associated with MetS.
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Diabetes Mellitus Tipo 2 , Síndrome Metabólico , Ratas , Animales , Ratas Endogámicas OLETF , Antagonistas de Receptores de Angiotensina , Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Ratas Long-Evans , Síndrome Metabólico/metabolismo , Encéfalo/metabolismo , Glucemia/metabolismoRESUMEN
INTRODUCTION: Multimorbidity is a prevalent worldwide problem among older adults. Our objective was to assess the association between life-course racial discrimination and multimorbidity among older adults in Colombia. METHODS: We used data from the SABE (Salud, Bienestar y Envejecimiento) Colombia Study in 2015 (N = 18,873), a national cross-sectional survey among adults aged 60 years or older. The outcome was multimorbidity, defined as having 2 or more chronic conditions. The main independent variables were 3 racial discrimination measures: 1) everyday racial discrimination (yes or no), 2) childhood racial discrimination score (scored from 0 [never] to 3 [many times]), and 3) situations of racial discrimination in the last 5 years (scored from 0 to 4 as a sum of the number of situations [group activities, public places, inside the family, health centers]). Other variables were sociodemographic characteristics, diseases, economic or health adversity during childhood, and functional status. We used weighted logistic regression analyses to adjust for differences between groups. RESULTS: Multivariate logistic regression models showed that multimorbidity was significantly associated with experiencing everyday racial discrimination (OR, 2.21; 95% CI, 1.62-3.02), childhood racial discrimination (OR, 1.27; 95% CI, 1.10-1.47), and the number of situations of racial discrimination (OR= 1.56; 95% CI, 1.22-2.00). Multimorbidity was also independently associated with multimorbidity during childhood. CONCLUSION: Racial discrimination experiences were associated with higher odds of multimorbidity among older adults in Colombia. Strategies to decrease life course experiences of racial discrimination may improve the health of older adults.
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Multimorbilidad , Racismo , Humanos , Anciano , Colombia/epidemiología , Estudios TransversalesRESUMEN
In Mexico City, the Canary Island date palm (Phoenix canariensis Chabaud) is an important plant forming part of its landscape identity. In February 2022, pink rot disease symptoms were observed on 16 P. canariensis plants in Mexico City (19°25'43.98"N, 99° 9'49.41"W). The incidence was 27%, while the severity 12%. External symptoms included necrotic lesions that advanced from the petiole towards the rachis. Internal symptoms were rotted, dark brown discoloration in bud, petiole, and rachis. Abundant conidial masses were developed on the infected tissues. Pieces of diseased tissues (5-mm cubes) were surface sterilized for 2 min in 3% sodium hypochlorite, rinsed with sterilized distilled water, plated onto potato dextrose agar (PDA), and incubated at 24°C and 12-h photoperiod, 20 pink fungal colonies were developed with sparse aerial mycelia on PDA. Conidiophores were hyaline, dimorphic, penicillate, and Acremonium-like. Conidia were dimorphic, typically with somewhat truncated ends, 4.5 to 5.7 × 1.9 to 2.3 µm (mean 4.99 × 2.15, n = 100), borne in long chains on penicillate conidiophores; on Acremonium-like conidiophores conidia were cylindrical, straight, and slightly curved, 4.55 to 10.1 × 1.2 to 2.35 µm (mean 8.2 × 1.7, n = 100). These morphological characteristics resembled those of Nalanthamala vermoesenii (Biourge) Schroers (Schroers et al. 2005). Genomic DNA was extracted from the mycelia of a representative isolate CP-SP53. The internal transcribed spacer (ITS) region and the large subunit of ribosomal ribonucleic acid (LSU) were amplified and sequenced. The sequences were deposited in GenBank with accession numbers OQ581472 (ITS) and OQ581465 (LSU). Phylogenetic trees based on ITS and LSU sequences of Nalanthamala species were reconstructed using maximum likelihood and Bayesian inference methods. Isolate CP-SP53 was placed in the clade of Nalanthamala vermoesenii. The pathogenicity test was carried out twice with isolate CP-SP53 on five 3-year-old P. canariensis plants. Four petioles per plant were surface disinfected with 75% ethanol, and wounded with a sterilized scalpel (shallow cuts 0.5 cm wide). A mycelial plug (5 mm in diam.) of a 1-week-old PDA culture was placed on each wounded site. Sterile PDA plugs were used for five non-inoculated control plants. All plants were maintained at 22 ± 2°C and a 12-h photoperiod. Twenty-five days after inoculation (dai), wounded petioles showed the same symptoms observed in the field, whereas control plants remained healthy. Forty-five dai, all inoculated plants died. Pink conidial masses developed on symptomatic tissues. To fulfill Koch's postulates, the pathogen was reisolated by placing the pink conidial masses onto PDA. The colony characteristics and morphometric measurements were identical to those of isolate CP-SP53. Nalanthamala vermoesenii has been reported on P. canariensis in Greece and United States (Feather et al. 1979; Ligoxigakis et al. 2013) and Syagrus romanzoffiana in Egypt (Mohamed et al. 2016). To our knowledge, this is the first report of Nalanthamala vermoesenii as the causal agent of pink rot on P. canariensis in Mexico. This plant is the most commonly planted ornamental palm in Mexico City. The spread of N. vermoesenii could be a threat for the estimated 15 thousand palms, therefore dramatically change the urban landscape.
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Fruits, vegetables, and spices are natural sources of bioactive phytochemicals, such as polyphenols, carotenoids, flavonoids, curcuminoids, terpenoids, and capsaicinoids, possessing multiple health benefits and relatively low toxicity. These compounds found in the diet play a central role in organism development and fitness. Given the complexity of the whole-body response to dietary changes, invertebrate model organisms can be valuable tools to examine the interplay between genes, signaling pathways, and metabolism. Drosophila melanogaster, an invertebrate model with its extensively studied genome, has more than 70% gene homology to humans and has been used as a model system in biological studies for a long time. The notable advantages of Drosophila as a model system, such as their low maintenance cost, high reproductive rate, short generation time and lifespan, and the high similarity of metabolic pathways between Drosophila and mammals, have encouraged the use of Drosophila in the context of screening and evaluating the impact of phytochemicals present in the diet. Here, we review the benefits of Drosophila as a model system for use in the study of phytochemical ingestion and describe the previously reported effects of phytochemical consumption in Drosophila.
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Drosophila melanogaster , Drosophila , Humanos , Animales , Carotenoides , Diarilheptanoides , Fitoquímicos/farmacología , MamíferosRESUMEN
To ensure soil quality and soil health, it is necessary to improve fertilization practices while minimizing environmental impacts. The aim of this study was to record the state of the art on soil fertility related to fertilization management (organic and/or mineral) and to detect environmental challenges in highly productive fields. A soil survey was set up in a new irrigated area (c. 20 years old), in the north-eastern part of Spain, which is mainly devoted to double annual crop rotations of cereals and maize. The area also supports an important animal rearing activity. The survey covered 733 ha of calcareous soils, owned by 35 farmers. At each farm, fertilization management was recorded, and soil was analyzed for nutrients and heavy metals. Multivariate analyses were performed. Total N, P, Cu and Zn, and available P, Cu, Zn and Mn soil concentrations were associated to the use of organic amendments. Heavy metals concentrations were below established thresholds. Available P (Olsen-P) was identified as an indicator of the previously adopted fertilization management and of the potential of P leaching towards deeper soil layers. Regression analyses were performed. A displacement of available P from the uppermost layer (0-0.3 m) occurs in the breakpoint of 86 mg P kg-1 soil. Preventative actions might be established from 53 mg P kg-1 soil due to the slowdown in P immobilization. Our results reinforce the importance of setting up P threshold soil levels for best practices of fertilization, as a basis for sustainable agriculture intensification.
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Metales Pesados , Suelo , Animales , Fósforo , Monitoreo del Ambiente , Región MediterráneaRESUMEN
Polyploidy has played a crucial role in plant evolution, development and function. Synthetic autopolyploid represents an ideal system to investigate the effects of polyploidization on transcriptional regulation. In this study, we deciphered the impact of genome duplication at phenotypic and molecular levels in watermelon. Overall, 88% of the genes in tetraploid watermelon followed a >1:1 dosage effect, and accordingly, differentially expressed genes were largely upregulated. In addition, a great number of hypomethylated regions (1688) were identified in an isogenic tetraploid watermelon. These differentially methylated regions were localized in promoters and intergenic regions and near transcriptional start sites of the identified upregulated genes, which enhances the importance of methylation in gene regulation. These changes were reflected in sophisticated higher-order chromatin structures. The genome doubling caused switching of 108 A and 626 B compartments that harbored genes associated with growth, development and stress responses.
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Cromatina/ultraestructura , Citrullus/genética , Duplicación de Gen/genética , Regulación de la Expresión Génica de las Plantas/genética , Cromatina/genética , Cromatina/metabolismo , Cromosomas de las Plantas/genética , Cromosomas de las Plantas/metabolismo , Cromosomas de las Plantas/ultraestructura , Citrullus/metabolismo , Epigenoma/genética , Estudios de Asociación Genética , Genoma de Planta/genética , Poliploidía , TetraploidíaRESUMEN
We identified biologically relevant moderators of response to tumor necrosis factor (TNF)-α inhibitor, infliximab, among 60 individuals with bipolar depression. Data were derived from a 12-week, randomized, placebo-controlled clinical trial secondarily evaluating the efficacy of infliximab on a measure of anhedonia (i.e., Snaith-Hamilton Pleasure Scale). Three inflammatory biotypes were derived from peripheral cytokine measurements using an iterative, machine learning-based approach. Infliximab-randomized participants classified as biotype 3 exhibited lower baseline concentrations of pro- and anti-inflammatory cytokines and soluble TNF receptor-1 and reported greater pro-hedonic improvements, relative to those classified as biotype 1 or 2. Pretreatment biotypes also moderated changes in neuroinflammatory substrates relevant to infliximab's hypothesized mechanism of action. Neuronal origin-enriched extracellular vesicle (NEV) protein concentrations were reduced to two factors using principal axis factoring: phosphorylated nuclear factorκB (p-NFκB), Fas-associated death domain (p-FADD), and IκB kinase (p-IKKα/ß) and TNF receptor-1 (TNFR1) comprised factor "NEV1," whereas phosphorylated insulin receptor substrate-1 (p-IRS1), p38 mitogen-activated protein kinase (p-p38), and c-Jun N-terminal kinase (p-JNK) constituted "NEV2". Among infliximab-randomized subjects classified as biotype 3, NEV1 scores were decreased at weeks 2 and 6 and increased at week 12, relative to baseline, and NEV2 scores increased over time. Decreases in NEV1 scores and increases in NEV2 scores were associated with greater reductions in anhedonic symptoms in our classification and regression tree model (r2 = 0.22, RMSE = 0.08). Our findings provide preliminary evidence supporting the hypothesis that the pro-hedonic effects of infliximab require modulation of multiple TNF-α signaling pathways, including NF-κB, IRS1, and MAPK.