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Human VSTM1 (also known as SIRL1) is an inhibitory immune checkpoint receptor involved in leukocyte activation. Identification of the homologous genes in other species, such as mice and rats, will undoubtedly contribute to functional studies and clinical applications. Here, we successfully cloned the Vstm1 gene in rats, as supported by high-throughput sequencing data. However, Vstm1 is degenerated to a pseudogene in the mouse genome. Rat Vstm1 mRNA contains a complete open reading frame (ORF) of 630 nucleotides encoding 209 amino acids. Rat Vstm1 is highly expressed in bone marrow, especially in granulocytes. The expression levels of Vstm1 gradually increase with the development of granulocytes in bone marrow but are downregulated in response to inflammatory stimuli. Rat VSTM1 does not have an immunoreceptor tyrosine-based inhibitory motif (ITIM), however, it shows a conservative function of inflammatory inhibition with human VSTM1, and both are anti-correlated with many inflammatory cytokines, such as IL-1α and TNF-α. In bone marrow-derived macrophages (BMDMs), either rat or human VSTM1 suppressed the secretion of inflammatory cytokines in response to LPS stimulation. Further analysis in lung cancer microenvironment revealed that VSTM1 is mainly expressed in myeloid cells, anti-correlated with inflammatory cytokines and associated with tumor development and metastasis.
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Citocinas , Macrófagos , Humanos , Ratos , Animais , Camundongos , Macrófagos/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , LipopolissacarídeosRESUMO
BACKGROUND: Indigenous chickens were developed through a combination of natural and artificial selection; essentially, changes in genomes led to the formation of these modern breeds via admixture events. However, their confusing genetic backgrounds include a genomic footprint regulating complex traits, which is not conducive to modern animal breeding. RESULTS: To better evaluate the candidate regions under domestication in indigenous chickens, we considered both runs of homozygosity (ROHs) and selective signatures in 13 indigenous chickens. The genomes of Silkie feather chickens presented the highest heterozygosity, whereas the highest inbreeding status and ROH number were found in Luhua chickens. Short ROH (< 1 Mb), were the principal type in all chickens. A total of 291 ROH islands were detected, and QTLdb mapping results indicated that body weight and carcass traits were the most important traits. An ROH on chromosome 2 covering VSTM2A gene was detected in 12 populations. Combined analysis with the Tajima's D index revealed that 18 genes (e.g., VSTM2A, BBOX1, and RYR2) were under selection and covered by ROH islands. Transcriptional analysis results showed that RYR2 and BBOX1 were specifically expressed in the heart and muscle tissue, respectively. CONCLUSION: Based on genome-wide scanning for ROH and selective signatures, we evaluated the genomic characteristics and detected significant candidate genes covered by ROH islands and selective signatures. The findings in this study facilitated the understanding of genetic diversity and provided valuable insights for chicken breeding and conservation strategies.
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Galinhas , Domesticação , Homozigoto , Animais , Galinhas/genética , Seleção Genética , Locos de Características Quantitativas , Genoma , Genômica/métodos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The majority of patients are diagnosed when ovarian cancer (OC) has metastasized, making surgery and chemotherapy less effective. Thus, there is an urgent need to elucidate the mechanisms underlying metastasis and to further explore novel diagnostic biomarkers of OC metastasis. Here, we conducted a genome-wide CRISPR-Cas9 screen for anoikis resistance to identify key genes associated with OC metastasis. Further, bioinformatic analysis was performed using TCGA and GTEx datasets to explore the genes associated with OC progression and prognosis. After integrated analysis, the V-set and transmembrane domain-containing protein 2-like (VSTM2L) was identified as a crucial gene closely associated with OC metastasis, progression, and prognosis. Further validation using a patient-based cohort suggested that VSTM2L expression was significantly higher in metastatic lesions than in primary lesions. Subsequently, an in vitro assay showed that VSTM2L silencing increased SKOV3 cell death and hampered spheroid formation. Mechanistically, GSEA highlighted that epithelial-mesenchymal transition (EMT)-related pathways was positively associated with VSTM2L expression. Consistently, the validation based on the VSTM2L silence suggested the involvement of VSTM2L in EMT-related TGF-ß and NF-κB signaling. Meanwhile, the addition of VSTM2L-containing medium did not provoke those signaling, indicating VSTM2L functions as an intracellular protein to activate TGF-ß and NF-κB signaling. In summary, our study revealed that VSTM2L is a novel player involved in anoikis resistance and is a promising biomarker of OC metastasis and prognosis.
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Anoikis , Neoplasias Ovarianas , Humanos , Feminino , Anoikis/genética , NF-kappa B/metabolismo , Neoplasias Ovarianas/patologia , Biomarcadores , Fator de Crescimento Transformador beta/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Proteínas do Tecido Nervoso/metabolismoRESUMO
In three experiments we investigated the effects of selective attention in iconic memory and fragile-visual short-term memory (VSTM), which have been related to phenomenal consciousness. We used a novel retro-cue paradigm with different delays (early vs late) and object priorities (high vs equal vs low), to investigate (a) attentional costs and benefits and the role of (b) bottom-up factors and (c) fragile-VSTM in feature-based attentional selection. Experiment 1 showed that attentional costs modulate visual maintenance at longer delays, while Experiment 2 showed that by reducing the time exposure of the memory array from 250 ms to 100 ms, as a bottom-up factor, participants were not able to select the objects based on their priorities. Finally, Experiment 3 showed that a pattern mask presented before the transfer in visual working memory, attenuates the overall performance while preserving the priority effect. The implications for phenomenal consciousness before conscious access are discussed.
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Atenção , Estado de Consciência , Humanos , Memória de Curto Prazo , Percepção Visual , Sinais (Psicologia)RESUMO
The V-set and transmembrane domain-containing protein (VSTM) family is a newly discovered immunoglobulin (Ig) superfamily that shares structural similarities with the B7-like transmembrane proteins. Although most VSTM5 members have been reported to exert immune-related functions, VSTM5 has been described as a regulator of neuronal morphogenesis and migration in the brain. Based on its close phylogenetic relationship with two immune checkpoints, VISTA and TIGIT, we investigated the potential role of VSTM5 in T-cell immune responses. VSTM5.Ig inhibits T-cell proliferation and cytokine production, induces T-cell apoptosis, and promotes the generation of regulatory T cells (Tregs) in in vitro T-cell assays. VSTM5 also contributes to the maintenance of T-cell anergy in vitro. Similarly, serum VSTM5.Ig produced using a recombinant plasmid in ovalbumin (OVA)-immunized mice inhibits both naive and effector T-cell immune responses. In addition, VSTM5.Ig enhances oral tolerance of cell-mediated and antibody responses in OVA-fed mice by inducing Tregs and T-cell clonal deletion. Consequently, our findings suggest that VSTM5 is a novel immune checkpoint that could be used to improve the therapeutic efficacy of tolerance-based therapies for autoimmune diseases.
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Formação de Anticorpos , Tolerância Imunológica , Proteínas de Membrana , Animais , Camundongos , Imunoglobulinas , Proteínas de Membrana/metabolismo , Ovalbumina , Filogenia , Linfócitos T ReguladoresRESUMO
BACKGROUND: Restless legs syndrome is a highly prevalent comorbidity of migraine; however, its genetic contributions remain unclear. OBJECTIVES: To identify the genetic variants of restless legs syndrome in migraineurs and to investigate their potential pathogenic roles. METHODS: We conducted a two-stage genome-wide association study (GWAS) to identify susceptible genes for restless legs syndrome in 1,647 patients with migraine, including 264 with and 1,383 without restless legs syndrome, and also validated the association of lead variants in normal controls unaffected with restless legs syndrome (n = 1,053). We used morpholino translational knockdown (morphants), CRISPR/dCas9 transcriptional knockdown, transient CRISPR/Cas9 knockout (crispants) and gene rescue in one-cell stage embryos of zebrafish to study the function of the identified genes. RESULTS: We identified two novel susceptibility loci rs6021854 (in VSTM2L) and rs79823654 (in CCDC141) to be associated with restless legs syndrome in migraineurs, which remained significant when compared to normal controls. Two different morpholinos targeting vstm2l and ccdc141 in zebrafish demonstrated behavioural and cytochemical phenotypes relevant to restless legs syndrome, including hyperkinetic movements of pectoral fins and decreased number in dopaminergic amacrine cells. These phenotypes could be partially reversed with gene rescue, suggesting the specificity of translational knockdown. Transcriptional CRISPR/dCas9 knockdown and transient CRISPR/Cas9 knockout of vstm2l and ccdc141 replicated the findings observed in translationally knocked-down morphants. CONCLUSIONS: Our GWAS and functional analysis suggest VSTM2L and CCDC141 are highly relevant to the pathogenesis of restless legs syndrome in migraineurs.
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Síndrome das Pernas Inquietas , Animais , Estudo de Associação Genômica Ampla , Humanos , Síndrome das Pernas Inquietas/complicações , Síndrome das Pernas Inquietas/genética , Peixe-Zebra/genéticaRESUMO
White adipose tissue (WAT) is a dynamic organ that plays crucial roles in controlling metabolic homeostasis. During development and periods of energy excess, adipose progenitors are recruited and differentiate into adipocytes to promote lipid storage capability. The identity of adipose progenitors and the signals that promote their recruitment are still incompletely characterized. We have recently identified V-set and transmembrane domain-containing protein 2A (VSTM2A) as a novel protein enriched in preadipocytes that amplifies adipogenic commitment. Despite the emerging role of VSTM2A in promoting adipogenesis, the molecular mechanisms regulating Vstm2a expression in preadipocytes are still unknown. To define the molecular mechanisms controlling Vstm2a expression, we have treated preadipocytes with an array of compounds capable of modulating established regulators of adipogenesis. Here, we report that Vstm2a expression is positively regulated by PI3K/mTOR and cAMP-dependent signaling pathways and repressed by the MAPK pathway and the glucocorticoid receptor. By integrating the impact of all the molecules tested, we identified signal transducer and activator of transcription 3 (STAT3) as a novel downstream transcription factor affecting Vstm2a expression. We show that activation of STAT3 increased Vstm2a expression, whereas its inhibition repressed this process. In mice, we found that STAT3 phosphorylation is elevated in the early phases of WAT development, an effect that strongly associates with Vstm2a expression. Our findings identify STAT3 as a key transcription factor regulating Vstm2a expression in preadipocytes.NEW & NOTEWORTHY cAMP-dependent and PI3K-mTOR signaling pathways promote the expression of Vstm2a. STAT3 is a key transcription factor that controls Vstm2a expression in preadipocytes. STAT3 is activated in the early phases of WAT development, an effect that strongly associates with Vstm2a expression.
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Adipócitos/fisiologia , Adipogenia/genética , Proteínas de Membrana/fisiologia , Fator de Transcrição STAT3/fisiologia , Células 3T3-L1 , Tecido Adiposo Branco/metabolismo , Animais , Diferenciação Celular/genética , Regulação da Expressão Gênica , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT3/genética , Transdução de Sinais/genéticaRESUMO
Although the PVR/TIGIT immune checkpoint axis has been suggested as a promising target for cancer immunotherapy and multiple TIGIT-targeting therapies are undergoing clinical trials, the underlying regulatory mechanisms of PVR/TIGIT interaction remain inconclusive. Here we show that TIGIT N-glycosylations are critical for maintaining the interaction between TIGIT and PVR. TIGIT has two N-glycosylation residues, N32 and N101. N-glycosylation on N101 of TIGIT and, to less extent, on N32, play potent roles in PVR binding. Taken together, these findings suggest that the N-glycosylation sites on TIGIT, especially residue N101, may be potential targets for PVR/TIGIT immune checkpoint blockade.
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Asparagina/metabolismo , Receptores Imunológicos/metabolismo , Receptores Virais/metabolismo , Sequência de Aminoácidos , Glicosilação , Células HEK293 , Humanos , Ligação Proteica , Receptores Imunológicos/químicaRESUMO
The aim of this study was to investigate the correlation between v-set and transmembrane domain-containing 1 (VSTM1) expression and incidence of major adverse cardiac events (MACE) in patients with coronary heart disease (CHD). A total of 310 patients were divided into a non-acute coronary syndrome (non-ACS) group (containing the stable angina group, and the asymptomatic coronary artery diseaseand other patients group) and an ACS group (containing unstable angina and acute myocardial infarction patients). Monocytic VSTM1 expression levels (assessed via average fluorescence intensity derived from antibody binding to VSTM1) in each group were detected and analyzed. The cut-off value of monocytic VSTM1 expression to predict the onset of ACS and MACE was confirmed. VSTM1 expression in monocytes from the ACS group was lower than that of the non-ACS group. The incidence of MACEs in the high VSTM1-expression group was much less than that of those in the low VSTM1 expression group at the 1 year follow-up stage. VSTM1 expression had an independent-inversed association with increased incidence of MACE and ACS. VSTM1 expression in monocytes may help to predict the occurrence of ACS in patients with CHD, and moreover it may provide the means to evaluate MACE prognosis during CHD patient follow-up.
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Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Infarto do Miocárdio , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Humanos , Monócitos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Prognóstico , Fatores de RiscoRESUMO
UNLABELLED: During brain development, dynamic changes in neuronal membranes perform critical roles in neuronal morphogenesis and migration to create functional neural circuits. Among the proteins that induce membrane dynamics, cell adhesion molecules are important in neuronal membrane plasticity. Here, we report that V-set and transmembrane domain-containing protein 5 (Vstm5), a cell-adhesion-like molecule belonging to the Ig superfamily, was found in mouse brain. Knock-down of Vstm5 in cultured hippocampal neurons markedly reduced the complexity of dendritic structures, as well as the number of dendritic filopodia. Vstm5 also regulates neuronal morphology by promoting dendritic protrusions that later develop into dendritic spines. Using electroporation in utero, we found that Vstm5 overexpression delayed neuronal migration and induced multiple branches in leading processes during corticogenesis. These results indicate that Vstm5 is a new cell-adhesion-like molecule and is critically involved in synaptogenesis and corticogenesis by promoting neuronal membrane dynamics. SIGNIFICANCE STATEMENT: Neuronal migration and morphogenesis play critical roles in brain development and function. In this study, we demonstrate for the first time that V-set and transmembrane domain-containing protein 5 (Vstm5), a putative cell adhesion membrane protein, modulates both the position and complexity of central neurons by altering their membrane morphology and dynamics. Vstm5 is also one of the target genes responsible for variations in patient responses to treatments for major depressive disorder. Our results provide the first evidence that Vstm5 is a novel factor involved in the modulation of the neuronal membrane and a critical element in normal neural circuit formation during mammalian brain development.
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Orientação de Axônios/fisiologia , Movimento Celular/fisiologia , Morfogênese/fisiologia , Neurogênese/fisiologia , Neurônios/citologia , Neurônios/fisiologia , Animais , Moléculas de Adesão Celular/metabolismo , Tamanho Celular , Células Cultivadas , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteínas de Membrana/metabolismo , CamundongosRESUMO
V-set and transmembrane domain-containing 1 (VSTM1), which is downregulated in bone marrow cells from leukemia patients, may provide a diagnostic and treatment target. Here, a triple-regulated oncolytic adenovirus was constructed to carry a VSTM1 gene expression cassette, SG611-VSTM1, and contained the E1a gene with a 24-nucleotide deletion within the CR2 region under control of the human telomerase reverse transcriptase promoter, E1b gene directed by the hypoxia response element, and VSTM1 gene controlled by the cytomegalovirus promoter. Real-time quantitative PCR and Western blot analyses showed that SG611-VSTM1 expressed VSTM1 highly efficiently in the human leukemic cell line K562 compared with SG611. In Cell Counting Kit-8 and flow cytometric assays, SG611-VSTM1 exhibited more potent anti-proliferative and pro-apoptotic effects in leukemic cells compared with SG611 and exerted synergistic cytotoxicity with low-dose daunorubicin (DNR) in vitro. In xenograft models, SG611-VSTM1 intratumorally injected at a dose of 1 × 10(9) plaque forming units combined with intraperitoneally injected low-dose DNR displayed significantly stronger antitumor effects than either treatment alone. Histopathologic examination revealed that SG611-VSTM1 induced apoptosis of leukemic cells. These results implicate an important role for VSTM1 in the pathogenesis of leukemia, and SG611-VSTM1 may be a promising agent for enhancing chemosensitivity in leukemia therapy.
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Adenoviridae/genética , Antineoplásicos/administração & dosagem , Daunorrubicina/administração & dosagem , Leucemia/terapia , Vírus Oncolíticos/genética , Receptores Imunológicos/genética , Adenoviridae/fisiologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Terapia Combinada , Feminino , Terapia Genética , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Humanos , Leucemia/tratamento farmacológico , Leucemia/fisiopatologia , Leucemia/virologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Terapia Viral Oncolítica , Vírus Oncolíticos/fisiologia , Receptores Imunológicos/metabolismoRESUMO
Our ability to hold information in mind is strictly limited. We sought to understand the relationship between oscillatory brain activity and the allocation of resources within visual short-term memory (VSTM). Participants attempted to remember target arrows embedded among distracters and used a continuous method of responding to report their memory for a cued target item. Trial-to-trial variability in the absolute circular accuracy with which participants could report the target was predicted by event-related alpha synchronization during initial processing of the memoranda and by alpha desynchronization during the retrieval of those items from VSTM. Using a model-based approach, we were also able to explore further which parameters of VSTM-guided behavior were most influenced by alpha band changes. Alpha synchronization during item processing enhanced the precision with which an item could be retained without affecting the likelihood of an item being represented per se (as indexed by the guessing rate). Importantly, our data outline a neural mechanism that mirrors the precision with which items are retained; the greater the alpha power enhancement during encoding, the greater the precision with which that item can be retained.
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Ritmo alfa , Memória de Curto Prazo/fisiologia , Percepção Visual , Adulto , Feminino , Humanos , MasculinoRESUMO
Despite our visual system receiving irrelevant input that competes with task-relevant signals, we are able to pursue our perceptual goals. Attention enhances our visual processing by biasing the processing of the input that is relevant to the task at hand. The top-down signals enabling these biases are therefore important for regulating lower level sensory mechanisms. In three experiments, we examined whether we apply similar biases to successfully maintain information in visual short-term memory (VSTM). We presented participants with targets alongside distracters and we graded their perceptual similarity to vary the extent to which they competed. Experiments 1 and 2 showed that the more items held in VSTM before the onset of the distracters, the more perceptually distinct the distracters needed to be for participants to retain the target accurately. Experiment 3 extended these behavioral findings by demonstrating that the perceptual similarity between target and distracters exerted a significantly greater effect on occipital alpha amplitudes, depending on the number of items already held in VSTM. The trade-off between VSTM load and target-distracter competition suggests that VSTM and perceptual competition share a partially overlapping mechanism, namely top-down inputs into sensory areas.
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Ritmo alfa/fisiologia , Atenção/fisiologia , Memória de Curto Prazo/fisiologia , Filtro Sensorial/fisiologia , Percepção Visual/fisiologia , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Inhibitory immune receptors set thresholds for immune cell activation, and their deficiency predisposes a person to autoimmune responses. However, the agonists of inhibitory immune receptors remain largely unknown, representing untapped sources of treatments for autoimmune diseases. Here, we show that V-set and transmembrane domain-containing 1 (VSTM1) is an inhibitory receptor and that its binding by the competent ligand soluble galectin-1 (Gal1) is essential for maintaining neutrophil viability mediated by downregulated reactive oxygen species production. However, in patients with systemic lupus erythematosus (SLE), circulating Gal1 is oxidized and cannot be recognized by VSTM1, leading to increased intracellular reactive oxygen species levels and reduced neutrophil viability. Dysregulated neutrophil function or death contributes significantly to the pathogenesis of SLE by providing danger molecules and autoantigens that drive the production of inflammatory cytokines and the activation of autoreactive lymphocytes. Interestingly, serum levels of glutathione, an antioxidant able to convert oxidized Gal1 to its reduced form, were negatively correlated with SLE disease activity. Taken together, our findings reveal failed inhibitory Gal1/VSTM1 pathway activation in patients with SLE and provide important insights for the development of effective targeted therapies.
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Lúpus Eritematoso Sistêmico , Neutrófilos , Humanos , Galectina 1 , Espécies Reativas de Oxigênio/metabolismoRESUMO
Background: Visual short-term memory (VSTM) and attention were found to modulate neural activity predominantly in a superior parietal lobule. This is thought to be the selective attention importance for encoding and manipulation in VSTM. The major area of investigation mainly rested with the differences in the neural substrates and networks mediating these cognitive processes in near and far cortical structures. Summary: Based on previous investigations, the dynamic temporal window route of attention and time locked associated cognitive processes and sub-processes are sketched and its implication in VSTM study is discussed. Imaging cortical structures to isolate closely linked cognitive tasks require circumscribing to certain time-windows in which the paradigm should support to tap time-locked associated processes and sub-processes. Key Messages: The neural activities in intraparietal sulcus area 1-2 and angular gyrus during VSTM encoding are beyond the modulatory effects of selective and sustained attention.
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INTRODUCTION: Previous findings have demonstrated that several Gestalt principles do facilitate VSTM performance in change detection tasks. However, few studies have investigated the role of and time-course of global-local consistency in motion perception. METHODS: Participants were required to track a moving target surrounded by three different backgrounds: blank, inconsistent, or consistent. Global-local objects were be bound to move together (covariation). During the PMT, participants had to follow the moving target with their eyes and react as fast as possible when the target had just vanished behind the obstruction or would arrive at a predetermined point of interception. Variable error (VE) and constant error (CE) of estimated time-to-contact (TTC) and gain of smooth pursuit eye movements were calculated in various conditions and analyzed qualitatively. RESULTS: Experiment 1 established the basic finding that VSTM performance could benefit from global-local consistency. Experiment 2 extended this finding by eye-tracking device. Both in visible phase and in occluded phase, CEs were smaller for the target in a consistent background than for the target in an inconsistent background and for the target in a blank background, with both differences significant (ps < .05). However, the difference in VE among three conditions was not significant. At early stage (100-250 ms), later stage (2750-3000 ms), and termination stage (5750-6000 ms) of smooth pursuit, the velocity gains were higher in the trials with consistent backgrounds than in the trials with inconsistent backgrounds and blank backgrounds (ps < .001). With the exception of 100-250 ms phase, the means did not differ between the inconsistent background and the blank background trials (ps > .1). CONCLUSIONS: Global-local consistency could be activated within the first few hundred milliseconds to prioritize the deployment of attention and eye movement to component target. Meanwhile, it also removes ambiguity from motion tracking and TTC estimation under some unpredictable conditions, leading to the consistency advantage during smooth-pursuit termination phase. Global-local consistency may act as an important information source to TTC estimation and oculomotor response in PMT.
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Percepção de Movimento , Acompanhamento Ocular Uniforme , Atenção/fisiologia , Movimentos Oculares , Humanos , Percepção de Movimento/fisiologia , Estimulação LuminosaRESUMO
Immunotherapy can improve survival in a variety of cancers by modulating the interaction between tumors and the tumor immune microenvironment (TIME). V-set and transmembrane domain containing 2 like (VSTM2L) regulates interleukin (IL)-4 signaling pathway-which involves immune-related factors-and has been linked to some cancers. However, the expression profile and prognostic significance of VSTM2L in different cancers as well as its relationship to the TIME are not known. This study investigated the pan-cancer expression profile, prognostic value, and immunologic relevance of VSTM2L. VSTM2L expression in different cancers was analyzed using the Cancer Cell Line Encyclopedia (CCLE), Human Protein Atlas (HPA), Tumor Immune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx) portal. We examined the association between VSTM2L expression and clinical outcomes by Kaplan-Meier and Cox regression analyses using TCGA and Kaplan-Meier Plotter, and the results were validated in a Gene Expression Omnibus cohort. The correlations between VSTM2L expression and immune cell infiltration, immunomodulators, tumor mutation burden (TMB), microsatellite instability (MSI), and immune and stromal scores across cancers were analyzed using TCGA, TIMER, and Tumor-Immune System Interactions and Drugbank databases (TISIDB). The results showed that VSTM2L expression varied across cancers and its aberrant expression was associated with clinical outcomes: upregulation of VSTM2L was positively associated with advanced stage and reduced overall survival (OS), disease-specific survival (DSS), progression-free interval (PFI), and disease-free interval (DFI) in stomach adenocarcinoma (STAD); and its upregulation was associated with early-stage disease and improved OS, DSS, PFI, and DFI in kidney renal papillary cell carcinoma (KIRP). VSTM2L expression level was correlated with immune cell infiltration, expression of immunomodulators, TMB, MSI, and immune and stromal scores in multiple cancers. In conclusion, VSTM2L has prognostic value in various cancers and can predict both poor (STAD) and good (KIRP) outcomes. The relationship between VSTM2L expression and immune markers suggests a role in modulating the TIME.
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OBJECTIVE: V-set and transmembrane domain-containing protein 1 (VSTM1) is negatively correlated with inflammation. However, its effect on atherosclerosis (AS) remains largely unexplored. In this study, we aimed to assess the effect of VSTM1 on the biological function of human peripheral blood mononuclear cells /macrophages stimulated by oxidized low-density lipoprotein (ox-LDL). METHODS: U937 cells were divided into three groups as follows: control group, pLenti-VSTM1 shRNA group (VSTM1 depletion), and pLenti-VSTM1 group (VSTM1 overexpression). Cellular migration, chemotaxis, apoptosis, and secretion of inflammatory factors of monocytes/macrophages stimulated by ox-LDL were studied. RESULTS: Overexpression of VSTM1 decreased the proliferation of U937 cells and induced cellular apoptosis. Depletion of VSTM1 enhanced the invasiveness and chemotaxis, increased the inflammatory response, and reduced the incidence of cell necrosis and apoptosis. Nuclear factor κ of B cells (NF-κB) was activated in VSTM1-depleted U937 cells. CONCLUSION: VSTM1 might play an important role in the activation of monocytes/macrophages and participate in the pathogenesis of AS via regulating NF-κB activity.
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Visual short-term memory (VSTM) is an important resource that allows temporarily storing visual information. Current theories posit that elementary features (e.g., red, green) are encoded and stored independently of each other in VSTM. However, they have difficulty explaining the similarity effect, that similar items can be remembered better than dissimilar items. In Experiment 1, we tested (N = 20) whether the similarity effect may be due to storing items in a context-dependent manner in VSTM (e.g., as the reddest/yellowest item). In line with a relational account of VSTM, we found that the similarity effect is not due to feature similarity, but to an enhanced sensitivity for detecting changes when the relative colour of a to-be-memorised item changes (e.g., from reddest to not-reddest item; than when an item underwent the same change but retained its relative colour; e.g., still reddest). Experiment 2 (N = 20) showed that VSTM load, as indexed by the CDA amplitude in the EEG, was smaller when the colours were ordered so that they all had the same relationship than when the same colours were out-of-order, requiring encoding different relative colours. With this, we report two new effects in VSTM - a relational detection advantage that describes an enhanced sensitivity to relative changes in change detection, and a relational CDA effect, which reflects that VSTM load, as indexed by the CDA, scales with the number of (different) relative features between the memory items. These findings support a relational account of VSTM and question the view that VSTM stores features such as colours independently of each other.
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Memória de Curto Prazo , Percepção Visual , Humanos , Rememoração MentalRESUMO
A power-space interaction, which denotes the phenomenon that people responded faster to powerful words with up cursor keys and faster to powerless words with down cursor keys, has been repeatedly found. In the present study, we took an individual differences approach to investigate how the power-space interaction is modulated by the spatial cognition. First, we found that the amplitude of power-space interaction was relatively stable within individuals across different stimuli. And, this individual difference in power-space interaction was correlated with the individual's spatial cognition, in such a way that participants with faster speed of mental rotation showed stronger power-space interactions. Our results shed new light on the cognitive mechanisms of the power-space associations by suggesting that spatial codes play an important role in the expression of such effect.