RESUMEN
The major and minor modes in Western music have positive and negative connotations, respectively. The present fMRI study examined listeners' neural responses to switches between major and minor modes. We manipulated the final chords of J. S. Bach's keyboard pieces so that each major-mode passage ended with either the major (Major-Major) or minor (Major-Minor) tonic chord, and each minor-mode passage ended with either the minor (Minor-Minor) or major (Minor-Major) tonic chord. If the final major and minor chords have positive and negative reward values respectively, the Major-Minor and Minor-Major stimuli would cause negative and positive reward prediction errors (RPEs) respectively in a listener's brain. We found that activity in a frontoparietal network was significantly higher for Major-Minor than for Major-Major. Based on previous research, these results support the idea that a major-to-minor switch causes negative RPE. The contrast of Minor-Major minus Minor-Minor yielded activation in the ventral insula and visual cortex, speaking against the idea that a minor-to-major switch causes positive RPE. We discuss our results in relation to executive functions and the emotional connotations of major versus minor modes.
Asunto(s)
Imagen por Resonancia Magnética , Música , Humanos , Imagen por Resonancia Magnética/métodos , Música/psicología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Emociones , Procesos Mentales , Percepción Auditiva/fisiologíaRESUMEN
Sugar is considered as the primary regulator of plant apical dominance, whereby the outgrowth of axillary buds is inhibited by the shoot tip. However, there are some deficiencies in this theory. Here, we reveal that Fatty Acid Export 6 (BnFAX6) functions in FA transport, and linoleic acid or its derivatives acts as a signaling molecule in regulating apical dominance of Brassica napus. BnFAX6 is responsible for mediating FA export from plastids. Overexpression of BnFAX6 in B. napus heightened the expression of genes involved in glycolysis and lipid biosynthesis, promoting the flow of photosynthetic products to the biosynthesis of FAs (including linoleic acid and its derivatives). Enhancing expression of BnFAX6 increased oil content in seeds and leaves and resulted in semi-dwarf and increased branching phenotypes with more siliques, contributing to increased yield per plant relative to wild-type. Furthermore, decapitation led to the rapid flow of the carbon from photosynthetic products to FA biosynthesis in axillary buds, consistent with the overexpression of BnFAX6 in B. napus. In addition, free FAs, especially linoleic acid, were rapidly transported from leaves to axillary buds. Increasing linoleic acid in axillary buds repressed expression of a key transcriptional regulator responsible for maintaining bud dormancy, resulting in bud outgrowth. Taken together, we uncovered that BnFAX6 mediating FA export from plastids functions in lipid biosynthesis and in axillary bud dormancy release, possibly through enhancing linoleic acid level in axillary buds of B. napus.
Asunto(s)
Brassica napus/genética , Ácidos Grasos/biosíntesis , Hojas de la Planta/crecimiento & desarrollo , Proteínas de Plantas/genética , Brassica napus/crecimiento & desarrollo , Brassica napus/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/metabolismoRESUMEN
Based on metabolic mechanism of scutellarin in vivo that scutellarin could be hydrolyzed into scutellarein by ß-glucuronide enzyme, some glucose-containing scutellarein derivatives were designed and synthesized through the introduction of glucose moiety at C-7 position of scutellarein via a glucosidic bond. Biological activity evaluation showed that these glucose-containing scutellarein derivatives exhibited potent DPPH radical scavenging activities. Furthermore, the improvement of physicochemical properties such as anticoagulant and neuroprotective activities alongside with the water solubility was achieved by introducing glucose. These findings suggest that the introduction of the glucose moiety to scutellarein wattants further development of this kind of compounds as neuroprotective agents.
Asunto(s)
Apigenina/química , Apigenina/metabolismo , Diseño de Fármacos , Glucosa/química , Glucuronatos/metabolismo , Fármacos Neuroprotectores/síntesis química , Animales , Anticoagulantes/síntesis química , Anticoagulantes/química , Anticoagulantes/metabolismo , Apigenina/síntesis química , Apigenina/farmacología , Sitios de Unión , Supervivencia Celular/efectos de los fármacos , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Peróxido de Hidrógeno/toxicidad , Simulación del Acoplamiento Molecular , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Células PC12 , Unión Proteica , Estructura Terciaria de Proteína , Ratas , Solubilidad , Trombina/antagonistas & inhibidores , Trombina/metabolismoRESUMEN
Two series of 8-aminomethylated derivatives were prepared by Mannich reaction of scutellarein (2) with appropriate aliphatic amines, alicyclic amines and formaldehyde. All the compounds were tested for their thrombin inhibition activity through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) assay using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay method and the solubility were assessed by ultraviolet (UV). The results showed that morpholinyl aminomethylene substituent derivative (3d) demonstrated stronger anticoagulant activity, better water solubility and good antioxidant activity compared with scutellarein (2), which warrants further development as a agent for ischemic cerebrovascular disease treatment.
Asunto(s)
Apigenina/química , Apigenina/farmacología , Trombina/antagonistas & inhibidores , Antioxidantes/síntesis química , Antioxidantes/química , Antioxidantes/farmacología , Apigenina/síntesis química , Diseño de Fármacos , Humanos , Bases de Mannich/líquido cefalorraquídeo , Bases de Mannich/química , Bases de Mannich/farmacología , Modelos Moleculares , Solubilidad , Relación Estructura-ActividadRESUMEN
Identifying biomarkers for abdominal aortic aneurysms (AAA) is key to understanding their pathogenesis, developing novel targeted therapeutics, and possibly improving patients outcomes and risk of rupture. Here, we identified AAA biomarkers from public databases using single-cell RNA-sequencing, weighted co-expression network (WGCNA), and differential expression analyses. Additionally, we used the multiple machine learning methods to identify biomarkers that differentiated large AAA from small AAA. Biomarkers were validated using GEO datasets. CIBERSORT was used to assess immune cell infiltration into AAA tissues and investigate the relationship between biomarkers and infiltrating immune cells. Therefore, 288 differentially expressed genes (DEGs) were screened for AAA and normal samples. The identified DEGs were mostly related to inflammatory responses, lipids, and atherosclerosis. For the large and small AAA samples, 17 DEGs, mostly related to necroptosis, were screened. As biomarkers for AAA, G0/G1 switch 2 (G0S2) (Area under the curve [AUC] = 0.861, 0.875, and 0.911, in GSE57691, GSE47472, and GSE7284, respectively) and for large AAA, heparinase (HPSE) (AUC = 0.669 and 0.754, in GSE57691 and GSE98278, respectively) were identified and further verified by qRT-PCR. Immune cell infiltration analysis revealed that the AAA process may be mediated by T follicular helper (Tfh) cells and the large AAA process may also be mediated by Tfh cells, M1, and M2 macrophages. Additionally, G0S2 expression was associated with neutrophils, activated and resting mast cells, M0 and M1 macrophages, regulatory T cells (Tregs), resting dendritic cells, and resting CD4 memory T cells. Moreover, HPSE expression was associated with M0 and M1 macrophages, activated and resting mast cells, Tregs, and resting CD4 memory T cells. Additional, G0S2 may be an effective diagnostic biomarker for AAA, whereas HPSE may be used to confer risk of rupture in large AAAs. Immune cells play a role in the onset and progression of AAA, which may improve its diagnosis and treatment.