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The incidence of skin cancer has been increasing over the past decades, and melanoma is considered highly malignant because of its high rate of metastasis. Plant-derived berberine, an isoquinoline quaternary alkaloid, has been reported to possess multiple pharmacological effects against various types of cancer cells. Therefore, we treated melanoma B16F10 cells with berberine to induce cell death and understand the cell death mechanisms. The berberine-treated cells showed decreased cell viability, according to berberine concentration. However, western blot analysis of apoptosis-related marker proteins showed that the expression of Bcl-2, an apoptosis inhibitory protein, and the Bcl-2/Bax ratio were increased. Therefore, by adding 3-methyladenine to the berberine-treated cells, we investigated whether the reduced cell viability was due to autophagic cell death. The results showed that 3-methyladenine restored the cell viability decreased by berberine, suggesting autophagy. To clarify autophagic cell death, we performed transmission electron microscopy analysis, which revealed the presence of autophagosomes and autolysosomes in the cells after treatment with berberine. Next, by analyzing the expression of autophagy-related proteins, we found an increase in the levels of light chain 3A-II and Atg12-Atg5 complex in the berberine-treated cells. We then assessed the involvement of the Akt/mTOR signaling pathway and found that berberine inhibited the expression of phosphorylated Akt and mTOR. Our data demonstrated that berberine induces autophagic cell death by inactivating the Akt/mTOR signaling pathway in melanoma cells and that berberine can be used as a possible target for the development of anti-melanoma drugs.
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Muerte Celular Autofágica , Berberina , Berberina/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteína X Asociada a bcl-2 , Apoptosis , Línea Celular Tumoral , Serina-Treonina Quinasas TOR/metabolismo , Transducción de Señal , Autofagia , Proteínas Reguladoras de la Apoptosis , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Relacionadas con la Autofagia/farmacología , Isoquinolinas/farmacologíaRESUMEN
We recently reported the biological evaluations of monovalent IAP antagonist 7 with good potency (MDA-MB-231, IC50 = 19 nM). In an effort to increase cellular activity and improve favorable drug-like properties, we newly designed and synthesized bivalent analogues based on quinazoline structure of 7. Optimization of cellular potency and CYP inhibition led to the identification of 27, which showed dramatic increase of over 100-fold (IC50 = 0.14 nM) and caused substantial tumor regressions in MDA-MB-231 xenograft model. These results strongly support 27 as a promising bivalent antagonist for the development of an effective anti-tumor approaches.
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Antineoplásicos/farmacología , Diseño de Fármacos , Proteínas Inhibidoras de la Apoptosis/antagonistas & inhibidores , Quinazolinas/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Perros , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Ratones , Estructura Molecular , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Quinazolinas/síntesis química , Quinazolinas/química , Ratas , Relación Estructura-ActividadRESUMEN
In June 2019, root mat disease was observed in hydroponically cultivated tomatoes in Jinju, South Korea, which occurred in at least 30% of the plants in the greenhouse. To isolate the causal bacteria, 10 g of infested tomato root mat sample was ground with 50 mL of sterile water. A 100-µL aliquot of the homogenate was serially diluted and spread on Mannitol-Glutamate (MG) medium amended with 0.1% yeast extract (MGY) and incubated at 28°C for 48 hours. Fifteen dominant colonies that formed on the MGY medium were purified and subjected to diagnostic polymerase chain reaction (PCR) based on the virD2-ipt gene loci. Because Ti-plasmid harbors both virD2 and ipt genes, Ri-plasmid-borne Agrobacterium species with only virD2 can be differentiated using virD2-ipt PCR. To amplify virD2, the primers 5'-ATG CCC GAT CGA GCT CAA GT-3' and 5'-TCG TCT GGC TGA CTT TCG TCA TAA-3' were used; for ipt amplification, the primers 5'-GAT CG(G/C) GTC CAA TG(C/T) TGT-3' and 5'-GAT ATC CAT CGA TC(T/C) CTT-3' were used. Amplification involved an initial 94°C for 1 min and then 40 cycles at 94°C, 50°C, and 72°C for 1 min at each temperature, with a final 5-min extension at 72°C. For three strains (GNIY2, J10, and J11), virD2 PCR products, but no ipt PCR products, were identified, indicating that three strains are Ri-plasmid-borne Agrobacterium species. A pathogenicity test was performed on 2-week-old tomato plants. Bacteria isolates (GNIY2, J10, and J11) cultured overnight in LB were made into a bacterial suspension (107 cfu/mL) in 50 mM phosphate buffer. Five tomato seedling roots were cut with sterilized scissors and soaked in each bacterial suspension for 1 hour. Phosphate buffer was used as a negative control. The inoculated tomato seedlings were transplanted in new pots and placed in a greenhouse with 25°C day and 20°C night temperature set points in natural light. After 9 weeks, all inoculated tomato plants produced overgrown roots, while the negative control plants had no symptoms. To satisfy Koch's postulates, re-isolation was performed from the diseased tomato and was the re-isolated bacteria were subject to partial 16S rDNA sequencing. Biovar tests performed as previously described revealed that all three isolates were biovar 1. A representative strain (GNIY2) was deposited in the Korean Agricultural Culture Collection (KACC 21759). To confirm the identity, four housekeeping genes of KACC 21759 were sequenced (16S rRNA, trpE, rpoB, and recA) and deposited in GenBank (accession nos. MT071560, MT444428, MT444429, and MT444430). Multilocus sequence analysis performed as previously described showed that the KACC 21759 strain was grouped in Agrobacterium genomospecies 4. This is the first report on mat root disease caused by Agrobacterium biovar 1 in hydroponic tomatoes in South Korea.
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Breeding new strains with improved traits is a long-standing goal of mushroom breeders that can be expedited by marker-assisted selection (MAS). We constructed a genetic linkage map of Pleurotus eryngii based on segregation analysis of markers in postmeiotic monokaryons from KNR2312. In total, 256 loci comprising 226 simple sequence-repeat (SSR) markers, 2 mating-type factors, and 28 insertion/deletion (InDel) markers were mapped. The map consisted of 12 linkage groups (LGs) spanning 1047.8cM, with an average interval length of 4.09cM. Four independent populations (Pd3, Pd8, Pd14, and Pd15) derived from crossing between four monokaryons from KNR2532 as a tester strain and 98 monokaryons from KNR2312 were used to characterize quantitative trait loci (QTL) for nine traits such as yield, quality, cap color, and earliness. Using composite interval mapping (CIM), 71 QTLs explaining between 5.82% and 33.17% of the phenotypic variations were identified. Clusters of more than five QTLs for various traits were identified in three genomic regions, on LGs 1, 7 and 9. Regardless of the population, 6 of the 9 traits studied and 18 of the 71 QTLs found in this study were identified in the largest cluster, LG1, in the range from 65.4 to 110.4cM. The candidate genes for yield encoding transcription factor, signal transduction, mycelial growth and hydrolase are suggested by using manual and computational analysis of genome sequence corresponding to QTL region with the highest likelihood odds (LOD) for yield. The genetic map and the QTLs established in this study will help breeders and geneticists to develop selection markers for agronomically important characteristics of mushrooms and to identify the corresponding genes.
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Ligamiento Genético , Marcadores Genéticos , Pleurotus/genética , Sitios de Carácter Cuantitativo/genética , Cruzamiento , Mapeo Cromosómico , Cruzamientos Genéticos , Repeticiones de Microsatélite/genética , Fenotipo , Pleurotus/crecimiento & desarrolloRESUMEN
In humans, the Crumbs homolog-1 (CRB1) gene is mutated in progressive types of autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. However, there is no clear genotype-phenotype correlation for CRB1 mutations, which suggests that other components of the CRB complex may influence the severity of retinal disease. Therefore, to understand the physiological role of the Crumbs complex proteins, we generated and analysed conditional knockout mice lacking CRB2 in the developing retina. Progressive disorganization was detected during late retinal development. Progressive thinning of the photoreceptor layer and sites of cellular mislocalization was detected throughout the CRB2-deficient retina by confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography. Under scotopic conditions using electroretinography, the attenuation of the a-wave was relatively stronger than that of the b-wave, suggesting progressive degeneration of photoreceptors in adult animals. Histological analysis of newborn mice showed abnormal lamination of immature rod photoreceptors and disruption of adherens junctions between photoreceptors, Müller glia and progenitor cells. The number of late-born progenitor cells, rod photoreceptors and Müller glia cells was increased, concomitant with programmed cell death of rod photoreceptors. The data suggest an essential role for CRB2 in proper lamination of the photoreceptor layer and suppression of proliferation of late-born retinal progenitor cells.
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Proteínas del Ojo/genética , Proteínas de la Membrana/genética , Mutación , Proteínas del Tejido Nervioso/genética , Retina/metabolismo , Retinitis Pigmentosa/genética , Animales , Apoptosis , Secuencia de Bases , Cartilla de ADN , Electrorretinografía , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Células Fotorreceptoras de Vertebrados/patología , Reacción en Cadena de la Polimerasa , Retina/crecimiento & desarrollo , Retinitis Pigmentosa/patología , Tomografía de Coherencia ÓpticaRESUMEN
Pleurotus ostreatus is a global mushroom crop with nutritional and medicinal benefits. However, the genetic basis of several commercial traits remains unknown. To address this, we analyzed the quantitative trait loci (QTLs) for two representative cultivars, "Heuktari" and "Miso," with apparently distinct alleles. A genetic map with 11 linkage groups was constructed, in which 27 QTLs were assigned to 14 traits. The explained phenotypic variations in QTLs ranged from 7.8% to 22.0%. Relatively high LOD values of 6.190 and 5.485 were estimated for the pinheading period and the number of valid stipes, respectively. Some QTL-derived molecular markers showed potential enhancement rates of selection precision in inbred lines, especially for cap shape (50%) and cap thickness (30%). Candidate genes were inferred from the QTL regions and validated using qRT-PCR, particularly for the cysteine and glutathione pathway, in relation to cap yellowness. The molecular markers in this study are expected to facilitate the breeding of the Heuktari and Miso lines and provide probes to identify related genes in P. ostreatus.
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Pleurotus , Sitios de Carácter Cuantitativo , Pleurotus/genética , Marcadores Genéticos , Mapeo Cromosómico , Ligamiento Genético , Fenotipo , AgriculturaRESUMEN
Backgrounds/Aims: Artificial intelligence (AI) technology has been used to assess surgery quality, educate, and evaluate surgical performance using video recordings in the minimally invasive surgery era. Much attention has been paid to automating surgical workflow analysis from surgical videos for an effective evaluation to achieve the assessment and evaluation. This study aimed to design a deep learning model to automatically identify surgical phases using laparoscopic cholecystectomy videos and automatically assess the accuracy of recognizing surgical phases. Methods: One hundred and twenty cholecystectomy videos from a public dataset (Cholec80) and 40 laparoscopic cholecystectomy videos recorded between July 2022 and December 2022 at a single institution were collected. These datasets were split into training and testing datasets for the AI model at a 2:1 ratio. Test scenarios were constructed according to structural characteristics of the trained model. No pre- or post-processing of input data or inference output was performed to accurately analyze the effect of the label on model training. Results: A total of 98,234 frames were extracted from 40 cases as test data. The overall accuracy of the model was 91.2%. The most accurate phase was Calot's triangle dissection (F1 score: 0.9421), whereas the least accurate phase was clipping and cutting (F1 score: 0.7761). Conclusions: Our AI model identified phases of laparoscopic cholecystectomy with a high accuracy.
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We propose on/offline hard example mining (HEM) techniques to alleviate the degradation of the generalization performance in the sparse distribution of events in non-relevant segment (NRS) recognition and to examine their utility for long-duration surgery. Through on/offline HEM, higher recognition performance can be achieved by extracting hard examples that help train NRS events, for a given training dataset. Furthermore, we provide two performance measurement metrics to quantitatively evaluate NRS recognition in the clinical field. The existing precision and recall-based performance measurement method provides accurate quantitative statistics. However, it is not an efficient evaluation metric in tasks where false positive recognition errors are fatal, such as NRS recognition. We measured the false discovery rate (FDR) and threat score (TS) to provide quantitative values that meet the needs of the clinical setting. Finally, unlike previous studies, the utility of NRS recognition was improved by applying our model to long-duration surgeries, instead of short-length surgical operations such as cholecystectomy. In addition, the proposed training methodology was applied to robotic and laparoscopic surgery datasets to verify that it can be robustly applied to various clinical environments.
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The oral consumption of capsicum has been reported to increase interleukin (IL)-2 and interferon (IFN)-γ production in Peyer's patches (PP); however, the active components responsible for these effects have not been completely identified. The beneficial biological effects of green peppers cultivated under environmentally friendly farming conditions (ECP), without the use of chemical pesticides, have rarely been compared with those of green peppers cultivated under conventional farming conditions (CCP). Oral administration of ECP extract significantly induced the production of IL-2 and IFN-γ in concanavalin A-treated cells from PP ex vivo; their levels were much higher than those in the CCP extract-treated group. A comparative analysis of the HPLC profiles indicated a 1.7-fold increase of a peak, named EF-1, at 415 nm in the ECP extract. The major component of EF-1 was identified as pheophytin a, which is a chlorophyll a molecule lacking a central Mg(2+) ion, as determined from NMR data. Intake of pheophytin a and chlorophyll a significantly increased IL-2 and IFN-γ production, and the percentage of IL-2- and IFN-γ-producing CD4+ T-cells in PP. Taken together, our data suggest that ECPs produce a higher content of pheophytin a than CCPs, and pheophytin a and chlorophyll a are immune-modulating components in green vegetables.
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Capsicum , Clorofila/farmacología , Interferón gamma/metabolismo , Interleucina-2/metabolismo , Ganglios Linfáticos Agregados/efectos de los fármacos , Feofitinas/farmacología , Agricultura/métodos , Animales , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Células Cultivadas , Clorofila/aislamiento & purificación , Clorofila A , Masculino , Ratones , Ratones Endogámicos C57BL , Ganglios Linfáticos Agregados/metabolismo , Feofitinas/aislamiento & purificación , Extractos Vegetales/químicaRESUMEN
People from independent cultures are more likely to causally explain others' behaviors by their disposition [vs. situation] compared to those from interdependent cultures. However, few studies have directly examined how these differences in attribution shape individuals' moral judgment, nor the underlying neural mechanisms of this process. Aiming to address these questions, in the scanner, participants rated the blameworthiness or praiseworthiness of protagonists who did either a negative or positive behavior, respectively. These behaviors were pretested and found to be perceived as dispositionally or situationally caused to different extents on average. Regardless of their self-construal, participants showed enhanced dorsomedial prefrontal cortex (dmPFC) activity in response to the behaviors that were evaluated as more situationally caused on average. Importantly, relatively independent participants reduced their blame for the behaviors that they showed greater dmPFC activity to. Relatively interdependent participants reduced blame for the behaviors that they themselves inferred more situational causes for, but dmPFC activity did not explain their blame. These findings suggest that while dmPFC might support relatively independent participants' effortful consideration of situational contributors to a behavior to make moral judgments, relatively interdependent participants might engage in this process automatically and relied less on dmPFC recruitment.
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Juicio , Imagen por Resonancia Magnética , Humanos , Juicio/fisiología , Principios Morales , Percepción Social , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiologíaRESUMEN
European Americans view high-intensity, open-mouthed 'excited' smiles more positively than Chinese because they value excitement and other high arousal positive states more. This difference is supported by reward-related neural activity, with European Americans showing greater Nucleus Accumbens (NAcc) activity to excited (vs calm) smiles than Chinese. But do these cultural differences generalize to all rewards, and are they related to real-world social behavior? European American (N = 26) and Chinese (N = 27) participants completed social and monetary incentive delay tasks that distinguished between the anticipation and receipt (outcome) of social and monetary rewards while undergoing Functional Magnetic Resonance Imaging (FMRI). The groups did not differ in NAcc activity when anticipating social or monetary rewards. However, as predicted, European Americans showed greater NAcc activity than Chinese when viewing excited smiles during outcome (the receipt of social reward). No cultural differences emerged when participants received monetary outcomes. Individuals who showed increased NAcc activity to excited smiles during outcome had friends with more intense smiles on social media. These findings suggest that culture plays a specific role in modulating reward-related neural responses to excited smiles during outcome, which are associated with real-world relationships.
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Emociones , Motivación , Humanos , Núcleo Accumbens/fisiología , Expresión Facial , Recompensa , Imagen por Resonancia MagnéticaRESUMEN
Surgical workflow analysis is essential to help optimize surgery by encouraging efficient communication and the use of resources. However, the performance of phase recognition is limited by the use of information related to the presence of surgical instruments. To address the problem, we propose visual modality-based multimodal fusion for surgical phase recognition to overcome the limited diversity of information such as the presence of instruments. Using the proposed methods, we extracted a visual kinematics-based index related to using instruments, such as movement and their interrelations during surgery. In addition, we improved recognition performance using an effective convolutional neural network (CNN)-based fusion method for visual features and a visual kinematics-based index (VKI). The visual kinematics-based index improves the understanding of a surgical procedure since information is related to instrument interaction. Furthermore, these indices can be extracted in any environment, such as laparoscopic surgery, and help obtain complementary information for system kinematics log errors. The proposed methodology was applied to two multimodal datasets, a virtual reality (VR) simulator-based dataset (PETRAW) and a private distal gastrectomy surgery dataset, to verify that it can help improve recognition performance in clinical environments. We also explored the influence of a visual kinematics-based index to recognize each surgical workflow by the instrument's existence and the instrument's trajectory. Through the experimental results of a distal gastrectomy video dataset, we validated the effectiveness of our proposed fusion approach in surgical phase recognition. The relatively simple yet index-incorporated fusion we propose can yield significant performance improvements over only CNN-based training and exhibits effective training results compared to fusion based on Transformers, which require a large amount of pre-trained data.
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The membrane-associated palmitoylated protein 5 (MPP5 or PALS1) is thought to organize intracellular PALS1-CRB-MUPP1 protein scaffolds in the retina that are involved in maintenance of photoreceptor-Müller glia cell adhesion. In humans, the Crumbs homolog 1 (CRB1) gene is mutated in progressive types of autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. However, there is no clear genotype-phenotype correlation for CRB1 mutations, which suggests that other components of the CRB complex may influence the severity of retinal disease. Therefore, to understand the physiological role of the Crumbs complex proteins, especially PALS1, we generated and analyzed conditional knockdown mice for Pals1. Small irregularly shaped spots were detected throughout the PALS1 deficient retina by confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography. The electroretinography a- and b-wave was severely attenuated in the aged mutant retinas, suggesting progressive degeneration of photoreceptors. The histological analysis showed abnormal retinal pigment epithelium structure, ectopic photoreceptor nuclei in the subretinal space, an irregular outer limiting membrane, half rosettes of photoreceptors in the outer plexiform layer, and a thinner photoreceptor synaptic layer suggesting improper photoreceptor cell layering during retinal development. The PALS1 deficient retinas showed reduced levels of Crumbs complex proteins adjacent to adherens junctions, upregulation of glial fibrillary acidic protein indicative of gliosis, and persisting programmed cell death after retinal maturation. The phenotype suggests important functions of PALS1 in the retinal pigment epithelium in addition to the neural retina.
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Proteínas de la Membrana/deficiencia , Proteínas de la Membrana/genética , Nucleósido-Fosfato Quinasa/deficiencia , Nucleósido-Fosfato Quinasa/genética , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/ultraestructura , Animales , Femenino , Masculino , Marmota , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Neuronas/metabolismo , Neuronas/ultraestructura , Oftalmoscopía , Retina/metabolismo , Retina/ultraestructura , Tomografía de Coherencia ÓpticaRESUMEN
Although the investigation of the neural mechanisms of morality has increased in recent years, the neural underpinnings of cultural variations in judgments of morality is understudied. In this paper, we propose that the well-established cultural differences in two cognitive processes, consideration of mental state and causal attribution, would lead to differences in moral judgment. Specifically, North Americans rely heavily on the mental state of a protagonist and dispositional attributions, whereas East Asians focus more on situational attributions and place less emphasis on the mental state of a protagonist. These differences would be accounted for by activity in brain regions implicated in thinking about others' minds, or theory-of-mind (ToM), which would underlie the cultural shaping of moral judgment. This proposed cultural neuroscience approach may broaden the scope of morality research, better predict moral behavior, and reduce disparities in diverse groups' moral judgment.
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Juicio , Teoría de la Mente , Humanos , Principios Morales , Percepción SocialRESUMEN
Parkinson's disease (PD) is the second most common neurodegenerative disorder and is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta. To discover potential key molecules in this process, we utilized cDNA microarray technology to obtain an expression profile of transcripts in MN9D dopaminergic neuronal cells treated with 6-hydroxydopamine. Using a self-organizing map algorithm, data mining and clustering were combined to identify distinct functional subgroups of genes. We identified alterations in the expression of 81 genes in eight clusters. Among these genes, we verified protein expression patterns of MAP kinase phosphatase 1 and sequestosome 1 using both cell culture and rat brain models of PD. Immunological analyses revealed increased expression levels as well as aggregated distribution patterns of these gene products in 6-hydroxydopamine-treated dopaminergic neurons. In addition to the identification of other proteins that are known to be associated with protein aggregation, our results raise the possibility that a more widespread set of proteins may be associated with the generation of protein aggregates in dying neurons. Further research to determine the functional roles of other altered gene products within the same cluster as well as the seven remaining clusters may provide new insights into the neurodegeneration that underlies PD pathogenesis.
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Neuronas Dopaminérgicas/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Degeneración Nerviosa/genética , Oxidopamina/toxicidad , Trastornos Parkinsonianos/genética , Sustancia Negra/efectos de los fármacos , Animales , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Línea Celular , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/patología , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica/fisiología , Masculino , Ratones , Degeneración Nerviosa/inducido químicamente , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Trastornos Parkinsonianos/patología , Ratas , Ratas Sprague-Dawley , Sustancia Negra/patologíaRESUMEN
How do people update their impressions of close others? Although people may be motivated to maintain their positive impressions, they may also update their impressions when their expectations are violated (i.e. prediction error). Combining neuroimaging and computational modeling, we test the hypothesis that brain regions associated with theory of mind, especially right temporoparietal junction (rTPJ), underpin both motivated impression maintenance and impression updating evoked by prediction error. Participants had money either given to or taken away from them by a friend or a stranger and were then asked to rate each partner on trustworthiness and closeness across trials. Overall, participants engaged in less impression updating for friends vs strangers. Decreased rTPJ activity in response to a friend's negative behavior (taking money) was associated with reduced negative updating and increased positive ratings of the friend. However, to the extent that participants did update their impressions (more negative ratings) of friends, this behavioral pattern was explained by greater prediction error and greater rTPJ activity. These findings suggest that rTPJ recruitment represents the integration of prediction error signals and the capacity to overcome people's motivation to maintain positive impressions of friends in the face of conflicting evidence.
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Mapeo Encefálico , Lóbulo Parietal , Encéfalo , Humanos , MotivaciónRESUMEN
There is an urgent need to find antidepressants that can be administered for long periods without inducing severe side effects to replace conventional antidepressants that control monoamine levels, such as tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and selective serotonin reuptake inhibitors (SSRI). We sought to determine the antidepressant effects of Fraxinus rhynchophylla Hance (F. rhynchophylla Hance, FX) and its components on a reserpine-induced mouse model. One hour after oral administration of FX (30, 50, and 100 mg/kg), esculin (50 mg/kg), esculetin (50 mg/kg), fraxin (50 mg/kg), and fluoxetine (20 mg/kg), reserpine was delivered intraperitoneally to mice. Behavioral experiments were conducted to measure anxiety and depressive-like behaviors after 10 days of administration. FX and its components increased the number of entries into the center of an open field as well as distance traveled within it and decreased immobility duration in the forced swim and tail suspension tests. Reserpine-induced increases in plasma corticosterone concentrations were attenuated by the administration of FX and its components, which were also found to decrease the reserpine-induced enhancement of mRNA levels of interleukin (IL)-12 p40, IL-6, and tumor necrosis factor (TNF)-α, pro-inflammatory cytokines. Finally, the diminished expressions of hippocampal phosphorylated cAMP response element-binding protein (pCREB) and brain-derived neurotrophic factor (BDNF) by reserpine were increased by FX and its components. Our results suggest that FX and its components regulate anxiety and depressive-like behaviors through stress hormones, immune regulation, and the activation of neuroprotective mechanisms, further supporting the potential of FX and its components as antidepressants.
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Is ingroup bias associated with any benefit for maintaining close relationships? We examined the link between biased impression updating for ingroup members (i.e., friends) and relationship maintenance, as measured by the number of friends participants reported having (Studies 1 and 2). We also investigated the underlying neural basis of this possible effect, focusing on activity in the right temporo-parietal junction (RTPJ), a region of the social brain involved in moral updating (Study 2). Specifically, we tested whether selectively discounting negative information about close others, manifested in reduced impression updating, and indexed by reduced RTPJ activity, is related to maintaining close relationships. In Study 1, after imagining a friend and a stranger performing different positive and negative behaviors, participants who were reluctant to update how close they felt to their friend (friend-closeness) reported having more friends in real life. In Study 2, participants were led to believe that a friend and a stranger gave money to them or took money away from them, while they were in the scanner. Participants who engaged in less negative updating of friends versus strangers reported having more friends. Participants who engaged in less friend-closeness updating also showed reduced RTPJ activity when their friend took money from them, and this neural pattern was associated with reports of having more friends. Together, these findings suggest that selectively discounting close others' negative behavior is linked to maintaining close relationships, indicating a potential social benefit of ingroup bias.
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People's beliefs about others are often impervious to new evidence: we continue to cooperate with ingroup defectors and refuse to see outgroup enemies as rehabilitated. Resistance to updating beliefs with new information has historically been interpreted as reflecting bias or motivated cognition, but recent work in Bayesian inference suggests that belief maintenance can be compatible with procedural rationality. We propose a mentalizing account of belief maintenance, which holds that protecting strong priors by generating alternative explanations for surprising information involves more mentalizing about the target than nonrational discounting. We review the neuroscientific evidence supporting this approach, and discuss how both types of processing can lead to fitness benefits.
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Cognición , Teorema de Bayes , HumanosRESUMEN
Why do people share resources with some strangers, but not others? This question becomes increasingly relevant as online platforms that promote lending world-wide proliferate (e.g., www.kiva.org). We predicted that lenders from nations that value excitement and other high-arousal positive states (HAP; e.g., United States) would loan more to borrowers who show excitement in their profile photos because the lenders perceive them to be more affiliative (e.g., trustworthy). As predicted, using naturally occurring Kiva data, lenders from the United States and Canada were more likely to lend money to borrowers (N = 13,500) who showed greater positive arousal (e.g., excitement) than were lenders from East Asian nations (e.g., Taiwan), above and beyond loan features (amount, repayment term; Study 1). In a randomly selected sample of Kiva lenders from 11 nations (N = 658), lenders from nations that valued HAP more were more likely to lend money to borrowers who showed open "excited" versus closed "calm" smiles, above and beyond other socioeconomic and cultural factors (Study 2). Finally, we examined whether cultural differences in lending were related to judgments of affiliation in an experimental study (Study 3, N = 103). Compared with Koreans, European Americans lent more to excited borrowers because they viewed them as more affiliative, regardless of borrowers' race (White, Asian) or sex (male, female). These findings suggest that people use their culture's affective values to decide with whom to share resources, and lend less to borrowers whose emotional expressions do not match those values, regardless of their race or sex. (PsycInfo Database Record (c) 2020 APA, all rights reserved).