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Phospholipase A2, group VII (PLA2G7) is widely recognized as a secreted, lipoprotein-associated PLA2 in plasma that converts phospholipid platelet-activating factor (PAF) to a biologically inactive product Lyso-PAF during inflammatory response. We report that intracellular PLA2G7 is selectively important for cell proliferation and tumor growth potential of melanoma cells expressing mutant NRAS, but not cells expressing BRAF V600E. Mechanistically, PLA2G7 signals through its product Lyso-PAF to contribute to RAF1 activation by mutant NRAS, which is bypassed by BRAF V600E. Intracellular Lyso-PAF promotes p21-activated kinase 2 (PAK2) activation by binding to its catalytic domain and altering ATP kinetics, while PAK2 significantly contributes to S338-phosphorylation of RAF1 in addition to PAK1. Furthermore, the PLA2G7-PAK2 axis is also required for full activation of RAF1 in cells stimulated by epidermal growth factor (EGF) or cancer cells expressing mutant KRAS. Thus, PLA2G7 and Lyso-PAF exhibit intracellular signaling functions as key elements of RAS-RAF1 signaling.
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Fosfolípidos , Proteínas Proto-Oncogénicas B-raf , Fosfolipasas A2 , Factor de Activación Plaquetaria/análogos & derivados , Factor de Activación Plaquetaria/metabolismoRESUMEN
Diet-derived nutrients are inextricably linked to human physiology by providing energy and biosynthetic building blocks and by functioning as regulatory molecules. However, the mechanisms by which circulating nutrients in the human body influence specific physiological processes remain largely unknown. Here we use a blood nutrient compound library-based screening approach to demonstrate that dietary trans-vaccenic acid (TVA) directly promotes effector CD8+ T cell function and anti-tumour immunity in vivo. TVA is the predominant form of trans-fatty acids enriched in human milk, but the human body cannot produce TVA endogenously1. Circulating TVA in humans is mainly from ruminant-derived foods including beef, lamb and dairy products such as milk and butter2,3, but only around 19% or 12% of dietary TVA is converted to rumenic acid by humans or mice, respectively4,5. Mechanistically, TVA inactivates the cell-surface receptor GPR43, an immunomodulatory G protein-coupled receptor activated by its short-chain fatty acid ligands6-8. TVA thus antagonizes the short-chain fatty acid agonists of GPR43, leading to activation of the cAMP-PKA-CREB axis for enhanced CD8+ T cell function. These findings reveal that diet-derived TVA represents a mechanism for host-extrinsic reprogramming of CD8+ T cells as opposed to the intrahost gut microbiota-derived short-chain fatty acids. TVA thus has translational potential for the treatment of tumours.
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Linfocitos T CD8-positivos , Neoplasias , Ácidos Oléicos , Animales , Bovinos , Humanos , Ratones , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Productos Lácteos , Ácidos Grasos Volátiles/farmacología , Ácidos Grasos Volátiles/uso terapéutico , Leche/química , Neoplasias/dietoterapia , Neoplasias/inmunología , Ácidos Oléicos/farmacología , Ácidos Oléicos/uso terapéutico , Carne Roja , OvinosRESUMEN
Mutant isocitrate dehydrogenase (IDH) 1 and 2 play a pathogenic role in cancers, including acute myeloid leukemia (AML), by producing oncometabolite 2-hydroxyglutarate (2-HG). We recently reported that tyrosine phosphorylation activates IDH1 R132H mutant in AML cells. Here, we show that mutant IDH2 (mIDH2) R140Q commonly has K413 acetylation, which negatively regulates mIDH2 activity in human AML cells by attenuating dimerization and blocking binding of substrate (α-ketoglutarate) and cofactor (NADPH). Mechanistically, K413 acetylation of mitochondrial mIDH2 is achieved through a series of hierarchical phosphorylation events mediated by tyrosine kinase FLT3, which phosphorylates mIDH2 to recruit upstream mitochondrial acetyltransferase ACAT1 and simultaneously activates ACAT1 and inhibits upstream mitochondrial deacetylase SIRT3 through tyrosine phosphorylation. Moreover, we found that the intrinsic enzyme activity of mIDH2 is much higher than mIDH1, thus the inhibitory K413 acetylation optimizes leukemogenic ability of mIDH2 in AML cells by both producing sufficient 2-HG for transformation and avoiding cytotoxic accumulation of intracellular 2-HG.
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Isocitrato Deshidrogenasa/genética , Leucemia Mieloide Aguda/metabolismo , Acetil-CoA C-Acetiltransferasa/metabolismo , Acetilación , Animales , Antineoplásicos/farmacología , Femenino , Humanos , Isocitrato Deshidrogenasa/metabolismo , Ácidos Cetoglutáricos/metabolismo , Leucemia Mieloide Aguda/genética , Lisina/genética , Lisina/metabolismo , Masculino , Ratones , Ratones Endogámicos NOD , Mutación/genética , NADP/metabolismo , Proteínas Nucleares/metabolismo , Fosforilación , Polimorfismo de Nucleótido Simple/genética , Cultivo Primario de Células , Unión Proteica , Procesamiento Proteico-Postraduccional , Proteínas Tirosina Quinasas/metabolismoRESUMEN
The oxidative pentose phosphate pathway (oxiPPP) contributes to cell metabolism through not only the production of metabolic intermediates and reductive NADPH but also inhibition of LKB1-AMPK signaling by ribulose-5-phosphate (Ru-5-P), the product of the third oxiPPP enzyme 6-phosphogluconate dehydrogenase (6PGD). However, we found that knockdown of glucose-6-phosphate dehydrogenase (G6PD), the first oxiPPP enzyme, did not affect AMPK activation despite decreased Ru-5-P and subsequent LKB1 activation, due to enhanced activity of PP2A, the upstream phosphatase of AMPK. In contrast, knockdown of 6PGD or 6-phosphogluconolactonase (PGLS), the second oxiPPP enzyme, reduced PP2A activity. Mechanistically, knockdown of G6PD or PGLS decreased or increased 6-phosphogluconolactone level, respectively, which enhanced the inhibitory phosphorylation of PP2A by Src. Furthermore, γ-6-phosphogluconolactone, an oxiPPP byproduct with unknown function generated through intramolecular rearrangement of δ-6-phosphogluconolactone, the only substrate of PGLS, bound to Src and enhanced PP2A recruitment. Together, oxiPPP regulates AMPK homeostasis by balancing the opposing LKB1 and PP2A.
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Proteínas Quinasas Activadas por AMP/metabolismo , Gluconatos/metabolismo , Neoplasias/enzimología , Proteína Fosfatasa 2/metabolismo , Células A549 , Quinasas de la Proteína-Quinasa Activada por el AMP , Animales , Proliferación Celular , Activación Enzimática , Glucosafosfato Deshidrogenasa/genética , Glucosafosfato Deshidrogenasa/metabolismo , Células HEK293 , Células HT29 , Humanos , Células K562 , Células MCF-7 , Ratones Desnudos , Neoplasias/genética , Neoplasias/patología , Células PC-3 , Vía de Pentosa Fosfato , Unión Proteica , Proteína Fosfatasa 2/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ribulosafosfatos/metabolismo , Transducción de Señal , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Carga Tumoral , Familia-src Quinasas/metabolismoRESUMEN
Piwi-interacting RNAs (piRNAs) engage Piwi proteins to suppress transposons and nonself nucleic acids and maintain genome integrity and are essential for fertility in a variety of organisms. In Caenorhabditis elegans, most piRNA precursors are transcribed from two genomic clusters that contain thousands of individual piRNA transcription units. While a few genes have been shown to be required for piRNA biogenesis, the mechanism of piRNA transcription remains elusive. Here we used functional proteomics approaches to identify an upstream sequence transcription complex (USTC) that is essential for piRNA biogenesis. The USTC contains piRNA silencing-defective 1 (PRDE-1), SNPC-4, twenty-one-U fouled-up 4 (TOFU-4), and TOFU-5. The USTC forms unique piRNA foci in germline nuclei and coats the piRNA cluster genomic loci. USTC factors associate with the Ruby motif just upstream of type I piRNA genes. USTC factors are also mutually dependent for binding to the piRNA clusters and forming the piRNA foci. Interestingly, USTC components bind differentially to piRNAs in the clusters and other noncoding RNA genes. These results reveal the USTC as a striking example of the repurposing of a general transcription factor complex to aid in genome defense against transposons.
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Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Regulación de la Expresión Génica/genética , ARN Interferente Pequeño/genética , Secuencias de Aminoácidos , Animales , Proteínas de Caenorhabditis elegans/genética , Genoma de los Helmintos/genética , Unión Proteica , Proteómica , ARN Interferente Pequeño/biosíntesisRESUMEN
Flexible fibers and textiles featuring photothermal conversion and storage capacities are ideal platforms for solar-energy utilization and wearable thermal management. Other than using fossil-fuel-based synthetic fibers, re-designing natural fibers with nanotechnology is a sustainable but challenging option. Herein, advanced core-shell structure fibers based on plant-based nanocelluloses are obtained using a facile co-axial wet-spinning process, which has superior photothermal and thermal-regulating performances. Besides serving as the continuous matrix, nanocelluloses also have two other important roles: dispersing agent when exfoliating molybdenum disulfide (MoS2), and stabilizer for phase change materials (PCM) in the form of Pickering emulsion. Consequently, the shell layer contains well-oriented nanocelluloses and MoS2, and the core layer contains a high content of PCM in a leak-proof encapsulated manner. Such a hierarchical cellulosic supportive structure leads to high mechanical strength (139 MPa), favorable flexibility, and large latent heat (92.0 J g-1), surpassing most previous studies. Furthermore, the corresponding woven cloth demonstrates satisfactory thermal-regulating performance, high solar-thermal conversion and storage efficiency (78.4-84.3%), and excellent long-term performance. In all, this work paves a new way to build advanced structures by assembling nanoparticles and polymers for functional composite fibers in advanced solar-energy-related applications.
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Chromosome conformation capture (3C) assays are used to map chromatin interactions genome-wide. Chromatin interaction maps provide insights into the spatial organization of chromosomes and the mechanisms by which they fold. Hi-C and Micro-C are widely used 3C protocols that differ in key experimental parameters including cross-linking chemistry and chromatin fragmentation strategy. To understand how the choice of experimental protocol determines the ability to detect and quantify aspects of chromosome folding we have performed a systematic evaluation of 3C experimental parameters. We identified optimal protocol variants for either loop or compartment detection, optimizing fragment size and cross-linking chemistry. We used this knowledge to develop a greatly improved Hi-C protocol (Hi-C 3.0) that can detect both loops and compartments relatively effectively. In addition to providing benchmarked protocols, this work produced ultra-deep chromatin interaction maps using Micro-C, conventional Hi-C and Hi-C 3.0 for key cell lines used by the 4D Nucleome project.
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Cromatina/química , Cromosomas Humanos/química , Reactivos de Enlaces Cruzados/química , Técnicas Genéticas , Línea Celular , Cromatina/metabolismo , Bases de Datos Factuales , Células Madre Embrionarias Humanas/citología , Células Madre Embrionarias Humanas/fisiología , HumanosRESUMEN
Non-small-cell lung carcinoma (NSCLC) is a type of pernicious tumor, which owns high morbidity and mortality. TRIM34 has a stimulative role in cell apoptosis and a suppressive role in inflammation. However, no studies were focused on the regulatory impacts of TRIM34 in NSCLC. This study aimed to examine the underlying regulatory effects of TRIM34 in NSCLC. TRIM34 exhibited lower expression in NSCLC. TRIM34 facilitated mitochondrial damage and apoptosis in NSCLC. TRIM34 induced the increased activity of mTORC1 and accelerated glycolysis in NSCLC. Enhanced mitochondrial damage induced by TRIM34 overexpression was reversed after rapamycin (mTORC1 inhibitor) treatment in NSCLC. The strengthened cell apoptosis stimulated by TRIM34 overexpression was rescued after rapamycin treatment. TRIM34 activated mTORC1 to suppress NSCLC progression in vivo. TRIM34 suppressed NSCLC via inducing mTORC1-dependent glucose utilization and promoting cellular death. The results suggest that TRIM34 can be a useful therapeutic biomarker for NSCLC patients.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Diana Mecanicista del Complejo 1 de la Rapamicina , Neoplasias Pulmonares/patología , Glucosa/metabolismo , Transducción de Señal , Línea Celular Tumoral , Sirolimus/farmacología , Sirolimus/uso terapéutico , Apoptosis , Proliferación Celular , Proteínas Portadoras/metabolismoRESUMEN
Myeloid-derived growth factor (MYDGF) is a cytokine that exhibits a variety of biological functions. This study focused on utilizing BL21(DE3) strain engineering and fermentation strategies to achieve high-level expression of soluble human MYDGF (hMYDGF) in Escherichia coli. Initially, the E. coli expressing strain BL21(DE3) was engineered by deleting the IpxM gene and inserting the GROEL/S and Trigger factor genes. The engineered E. coli strain BL21(TG)/pT-MYDGF accumulated 3557.3 ± 185.6 µg/g and 45.7 ± 6.7 mg/L of soluble hMYDGF in shake flask fermentation, representing a 15.6-fold increase compared to the control strain BL21(DE3)/pT-MYDGF. Furthermore, the yield of hMYDGF was significantly enhanced by optimizing the fermentation conditions. Under optimized conditions, the 5L bioreactor yielded up to 2665.8 ± 164.3 µg/g and 407.6 ± 42.9 mg/L of soluble hMYDGF. The results indicate that the implementation of these optimization strategies could enhance the ratio and yield of soluble proteins expressed by E.coli, thereby meeting the demands of industrial production. This study employed sophisticated strategies to lay a solid foundation for the industrial application of hMYDGF.
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Escherichia coli , Fermentación , Proteínas Recombinantes , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Proteínas Recombinantes/genética , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/metabolismo , Solubilidad , Reactores Biológicos , Expresión GénicaRESUMEN
PURPOSE: Diabetes is a chronic disease in metabolic disorder, and the pathology is characterized by insulin resistance and insulin secretion disorder in blood. In current, many studies have revealed that polysaccharides extracted from natural sources with significant anti-diabetic effects. Natural polysaccharides can ameliorate diabetes through different action mechanisms. All these polysaccharides are expected to have an important role in the clinic. METHODS: Existing polysaccharides for the treatment of diabetes are reviewed, and the mechanism of polysaccharides in the treatment of diabetes and its structural characteristics are described in detail. RESULTS: This article introduced the natural polysaccharide through different mechanisms of action in the treatment of diabetes, including oxidative stress, apoptosis, inflammatory response and regulation of intestinal bacteria. Natural polysaccharides can treat of diabetes by regulating signaling pathways is also a research hotspot. In addition, the structural characteristics of polysaccharides were explored. There are some structure-activity relationships between natural polysaccharides and the treatment of diabetes.
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Diabetes Mellitus , Resistencia a la Insulina , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/química , Diabetes Mellitus/tratamiento farmacológico , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Polisacáridos/química , Estrés OxidativoRESUMEN
Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) regulates pyruvate dehydrogenase complex (PDC) by acetylating pyruvate dehydrogenase (PDH) and PDH phosphatase. How ACAT1 is "hijacked" to contribute to the Warburg effect in human cancer remains unclear. We found that active, tetrameric ACAT1 is commonly upregulated in cells stimulated by EGF and in diverse human cancer cells, where ACAT1 tetramers, but not monomers, are phosphorylated and stabilized by enhanced Y407 phosphorylation. Moreover, we identified arecoline hydrobromide (AH) as a covalent ACAT1 inhibitor that binds to and disrupts only ACAT1 tetramers. The resultant AH-bound ACAT1 monomers cannot reform tetramers. Inhibition of tetrameric ACAT1 by abolishing Y407 phosphorylation or AH treatment results in decreased ACAT1 activity, leading to increased PDC flux and oxidative phosphorylation with attenuated cancer cell proliferation and tumor growth. These findings provide a mechanistic understanding of how oncogenic events signal through distinct acetyltransferases to regulate cancer metabolism and suggest ACAT1 as an anti-cancer target.
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Acetil-CoA C-Acetiltransferasa/metabolismo , Mitocondrias/enzimología , Complejo Piruvato Deshidrogenasa/metabolismo , Acetil-CoA C-Acetiltransferasa/genética , Animales , Línea Celular Tumoral , Proliferación Celular , Factor de Crecimiento Epidérmico/metabolismo , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Ratones Desnudos , Células 3T3 NIH , Neoplasias/enzimología , Neoplasias/patología , Oligopéptidos/genética , Oligopéptidos/metabolismo , Fosforilación , Proteínas Tirosina Quinasas/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismoRESUMEN
BACKGROUND: Approximately half of all patients with hepatocellular carcinoma (HCC) develop cachexia during the course of the disease. It is important to be able to predict which patients will develop cachexia at an early stage. PURPOSE: To develop and validate a nomogram based on the magnetic resonance imaging (MRI) features of HCC and body composition for potentially predicting cachexia in patients with HCC. MATERIAL AND METHODS: A retrospective two-center study recruited the pretreatment clinical and MRI data of 411 patients with HCC undergoing abdominal MRI. The data were divided into three cohorts for development, internal validation, and external validation. Patients were followed up for six months after the MRI scan to record each patient's weight to diagnose cachexia. Logistic regression analyses were performed to identify independent variables associated with cachexia in the development cohort used to build the nomogram. RESULTS: The multivariable analysis suggested that the MRI parameters of tumor size > 5â cm (P = 0.001), intratumoral artery (P = 0.004), skeletal muscle index (P < 0.001), and subcutaneous fat area (P = 0.004) were independent predictors of cachexia in patients with HCC. The nomogram derived from these parameters in predicting cachexia reached an area under receiver operating characteristic curve of 0.819, 0.783, and 0.814 in the development, and internal and external validation cohorts, respectively. CONCLUSION: The proposed multivariable nomogram suggested good performance in predicting the risk of cachexia in HCC patients.
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Composición Corporal , Caquexia , Carcinoma Hepatocelular , Neoplasias Hepáticas , Imagen por Resonancia Magnética , Nomogramas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/complicaciones , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/complicaciones , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Caquexia/diagnóstico por imagen , Caquexia/etiología , Estudios Retrospectivos , Anciano , Valor Predictivo de las Pruebas , AdultoRESUMEN
Utilizing iron chloride as a Lewis acid catalyst, we developed a straightforward and mild oxidative cross-coupling reaction between quinoxalinones and indoles, yielding a series of versatile 3-(indol-3-yl)quinoxalin-2-one derivatives. This approach allows for the incorporation of a wide array of functional groups into the final products, demonstrating its synthetic versatility. Notably, the method was successfully scaled up to gram-scale reactions while maintaining high yields. Our mechanistic investigation indicates that iron chloride serves as a catalyst to facilitate the formation of key intermediates which subsequently undergo oxidation to afford the desired products. The merits of this protocol include its cost effectiveness, operational simplicity, and the ease of product isolation via filtration.
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Photoacoustic imaging (PAI) is an emerging modality in biomedical imaging with superior imaging depth and specificity. However, PAI still has significant limitations, such as the background noise from endogenous chromophores. To overcome these limitations, we developed a covalent activity-based PAI probe, NOx-JS013, targeting NCEH1. NCEH1, a highly expressed and activated serine hydrolase in aggressive cancers, has the potential to be employed for the diagnosis of cancers. We show that NOx-JS013 labels active NCEH1 in live cells with high selectivity relative to other serine hydrolases. NOx-JS013 also presents its efficacy as a hypoxia-responsive imaging probe in live cells. Finally, NOx-JS013 successfully visualizes aggressive prostate cancer tumors in mouse models of PC3, while being negligibly detected in tumors of non-aggressive LNCaP mouse models. These findings show that NOx-JS013 has the potential to be used to develop precision PAI reagents for detecting metastatic progression in various cancers.
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Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates. Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity. This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes. The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes, and corresponding reference ranges will be established. The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance, with altitude gradients divided into 4 categories: 800 m, 1 900 m, 2 400 m, and 3 500 m, with an anticipated sample size of 170 neonates per altitude gradient. This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.
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Altitud , Encéfalo , Electroencefalografía , Oxígeno , Humanos , Recién Nacido , Encéfalo/metabolismo , Oxígeno/metabolismo , Espectroscopía Infrarroja Corta , Estudios ProspectivosRESUMEN
Proper regulation of microtubule (MT) stability and dynamics is vital for essential cellular processes, including axonal transportation and synaptic growth and remodeling in neurons. In the present study, we demonstrate that the Drosophila ankyrin repeat and KH domain-containing protein Mask negatively affects MT stability in both larval muscles and motor neurons. In larval muscles, loss-of-function of mask increases MT polymer length, and in motor neurons, loss of mask function results in overexpansion of the presynaptic terminal at the larval neuromuscular junctions (NMJs). mask genetically interacts with stathmin (stai), a neuronal modulator of MT stability, in the regulation of axon transportation and synaptic terminal stability. Our structure-function analysis of Mask revealed that its ankyrin repeats domain-containing N-terminal portion is sufficient to mediate Mask's impact on MT stability. Furthermore, we discovered that Mask negatively regulates the abundance of the MT-associated protein Jupiter in motor neuron axons, and that neuronal knocking down of Jupiter partially suppresses mask loss-of-function phenotypes at the larval NMJs. Taken together, our studies demonstrate that Mask is a novel regulator for MT stability, and such a role of Mask requires normal function of Jupiter.
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Proteínas de Drosophila , Drosophila melanogaster , Animales , Repetición de Anquirina , Proteínas de Unión al ADN/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Microtúbulos/metabolismo , Neuronas Motoras/metabolismoRESUMEN
BACKGROUND: Due to their location and growth patterns, retroperitoneal tumors often involve the surrounding blood vessels. Clinical decisions on a proper treatment depend on the information on this condition. Evaluation of blood vessels using non-contrast-enhanced vessel wall MRI may provide noninvasive assessment of the extent of tumor invasion to assist clinical decision-making. PURPOSE: To investigate the performance and potential of non-contrast-enhanced vessel wall MRI in evaluating the degree of vessel wall invasion of retroperitoneal tumors. STUDY TYPE: Prospective. POPULATION: Thirty-seven participants (mean age: 60.59 ± 11.77 years, 59% male) with retroperitoneal tumors close to vessels based on their diagnostic computer tomography. FIELD STRENGTH/SEQUENCES: 3 T; vessel wall MRI sequences: two-dimensional T2-weighted MultiVane XD turbo spin-echo (2D-T2-MVXD-TSE) and three-dimensional T1-weighted motion sensitized driven equilibrium fat suppression turbo spin-echo (3D-T1-MSDE-TSE) sequences; conventional MRI sequences: T2-weighted fat suppression turbo spin-echo (T2-FS-TSE), T2-weighted turbo spin-echo (T2-TSE), modified Dixon T1-weighted fast field echo (T1-mDixon-FFE), and diffusion-weighted echo planar imaging (DWI-EPI) sequences. ASSESSMENT: All patients underwent preoperative imaging using both non-contrast conventional and vessel wall MRI sequences. Images obtained from conventional and vessel wall MRI sequences were evaluated independently by three junior radiologists (3 and 2 years of experience in reading MRI) and reviewed by one senior radiologist (25 years of experience in reading MRI) to assess the degree of vessel wall invasion. MRI were validated results from the clinical standard diagnosis based on surgical confirmation or histopathological reports. Interobserver agreement was determined based on the reports from three readers with similar years of experiences. Intraobserver variability was assessed based on categorizing and recategorizing the vessels of 37 patients 1 month apart. STATISTICAL TESTS: Intra-class correlation efficient (ICC), Chi-square test, McNemar test, area under the receiver-operating characteristic curve (AUC), Delong test, P < 0.05 was considered significant. RESULTS: The accuracy of vessel wall MRI (91.96%, 95% CI: 85.43-95.71; 103 of 112) in detecting the degree of vessel wall invasion was significantly higher than that of conventional MRI (75%, 95% CI: 66.24-82.10; 84 of 112). The interobserver variability or reproducibility in categorization of the degree of vascular wall invasion was good in evaluating images from conventional and vessel wall MRI sequences (ICC = 0.821, 95% CI: 0.765-0.867 and ICC = 0.881, 95% CI: 0.842-0.913, respectively). DATA CONCLUSION: Diagnosis of vessel wall invasion of retroperitoneal tumors and assessment of its severity can be improved by using non-contrast-enhanced vessel wall MRI. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.
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OBJECTIVES: This study aims to investigate and develop imaging biomarkers for the diagnosis of cancer-associated cachexia based on the organ and tissue-specific abnormal metabolisms measured by fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT. METHODS: FDG PET/CT data from 390 cancer patients were analyzed retrospectively. Patients were divided into a development cohort and a validation cohort. Cachexia was defined as weight loss > 5% in 6 months or BMI < 20 and weight loss > 2%. According to the above definitions, patients were divided into cachexia and non-cachexia groups. Results of the clinical laboratory tests for metabolic levels and organ and tissue-specific FDG uptake obtained from the cachexia and non-cachexia groups were compared statistically. Logistic regression analysis was performed to identify independent variables associated with cachexia in the development cohort for generating the regression model. The performance of the model was tested using the data from a validation cohort and evaluated by area under the receiver operating characteristic curve (AUC). RESULTS: Based on the data from the development cohort of 286 patients and a validation cohort of 104 patients, it is found that age, white blood cell count, peak standardized uptake value (SUV) of the liver, and minimum SUV of lean body mass of visceral fat and subcutaneous fat were independently associated with cachexia. The model incorporating these variables reached an AUC of 0.777 (95% confidence interval (CI): 0.721, 0.833) in the development cohort and an AUC of 0.729 (95% CI: 0.629, 0.829) in the validation cohort. CONCLUSION: Organ and tissue-specific abnormal glucose metabolism as measured by PET/CT can be used as a biomarker for cancer-associated cachexia. KEY POINTS: ⢠Patients with cancer-associated cachexia have reduced FDG uptake in the liver and increased FDG uptake in visceral fat and subcutaneous fat. ⢠FDG uptake of the liver, visceral fat, and subcutaneous fat can be independent risk factors for identifying cancer-associated cachexia. ⢠Cancer-associated cachexia can be classified using the model that incorporates age, white blood cell count, FDG uptake of the liver, and visceral and subcutaneous fat can diagnose with an AUC of 0.729.
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Fluorodesoxiglucosa F18 , Neoplasias , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos , Estudios Retrospectivos , Neoplasias/complicaciones , Biomarcadores , Hígado , Obesidad , Pérdida de PesoRESUMEN
Candidatus Methanoperedens-like archaea, which can use multiple electron acceptors (nitrate, iron, manganese, and sulfate) for anaerobic methane oxidation, could play an important role in reducing methane emissions from freshwater wetlands. Currently, very little is known about the distribution and community composition of Methanoperedens-like archaea in freshwater wetlands, particularly based on their alpha subunit of methyl-coenzyme M reductase (mcrA) genes. Here, the community composition, diversity, and abundance of Methanoperedens-like archaea were investigated in a freshwater wetland through high-throughput sequencing and quantitative PCR on their mcrA genes. A large number of Methanoperedens-like mcrA gene sequences (119,250) were recovered, and a total of 31 operational taxonomic units (OTUs) were generated based on 95% sequence similarity cut-off. The majority of Methanoperedens-like sequences can be grouped into three distinct clusters that were closely associated with the known Methanoperedens species which can couple anaerobic methane oxidation to nitrate or iron reduction. The community composition of Methanoperedens-like archaea differed significantly among different sampling sites, and their mcrA gene abundance was 1.49 × 106 ~ 4.62 × 106 copies g-1 dry soil in the examined wetland. In addition, the community composition of Methanoperedens-like archaea was significantly affected by the soil water content, and the archaeal abundance was significantly positively correlated with the water content. Our results suggest that the mcrA gene is a good biomarker for detection and quantification of Methanoperedens-like archaea, and provide new insights into the distribution and environmental regulation of these archaea in freshwater wetlands.
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Archaea , Humedales , Archaea/genética , Nitratos , Suelo , Filogenia , Oxidación-Reducción , Agua Dulce , Metano , Agua , Hierro , AnaerobiosisRESUMEN
According to previous published works, precise modeling of the first dimensional (1D) peak in comprehensive two-dimensional gas chromatography (GC × GC) requires at least 3 modulated sub-peaks (MSP). This requirement is sometimes difficult to meet, e.g., in case of undersampling modulation. In the present work, the feasibility of modeling of the 1D peak with only 2 MSP was demonstrated. The effects of modulation phase (Ï), modulation period (PM), the peak width (1σ), and the peak shape of the original 1D peak on the accuracy of the proposed method were explored. When employing PM ranging from 6 s ~ 3 s to modulate original peaks with 1σ = 1.2 s ~ 0.6 s, the maximal error of the modeled 1tR is 1.08 s, which is far less than the error generated by employing the largest MSP to estimate the 1tR. The deviation of modeled 1tR increases with the increase of peak shape distortion, and this deviation is ≤ 0.67 s when tailing factor (Tf) in the range of 0.8 to 1.5. The application of the proposed method was demonstrated by assisting identification of a monoterpene in Myrrh sample. The proposed approach could improve the accuracy in calculation of 1tR or 1I and enhance the reliability of compound identification in GC × GC analysis with undersampling modulation.