RESUMO
The language network of the human brain has core components in the inferior frontal cortex and superior/middle temporal cortex, with left-hemisphere dominance in most people. Functional specialization and interconnectivity of these neocortical regions is likely to be reflected in their molecular and cellular profiles. Excitatory connections between cortical regions arise and innervate according to layer-specific patterns. Here, we generated a gene expression dataset from human postmortem cortical tissue samples from core language network regions, using spatial transcriptomics to discriminate gene expression across cortical layers. Integration of these data with existing single-cell expression data identified 56 genes that showed differences in laminar expression profiles between the frontal and temporal language cortex together with upregulation in layer II/III and/or layer V/VI excitatory neurons. Based on data from large-scale genome-wide screening in the population, DNA variants within these 56 genes showed set-level associations with interindividual variation in structural connectivity between the left-hemisphere frontal and temporal language cortex, and with the brain-related disorders dyslexia and schizophrenia which often involve affected language. These findings identify region-specific patterns of laminar gene expression as a feature of the brain's language network.
Assuntos
Idioma , Neocórtex , Humanos , Neocórtex/metabolismo , Lobo Temporal/metabolismo , Masculino , Feminino , Esquizofrenia/genética , Esquizofrenia/metabolismo , Neurônios/metabolismo , Lobo Frontal/metabolismo , Transcriptoma , AdultoRESUMO
Understanding the evolutionarily conserved feature of functional laterality in the habenula has been attracting attention due to its potential role in human cognition and neuropsychiatric disorders. Deciphering the structure of the human habenula remains to be challenging, which resulted in inconsistent findings for brain disorders. Here, we present a large-scale meta-analysis of the left-right differences in the habenular volume in the human brain to provide a clearer picture of the habenular asymmetry. We searched PubMed, Web of Science, and Google Scholar for articles that reported volume data of the bilateral habenula in the human brain, and assessed the left-right differences. We also assessed the potential effects of several moderating variables including the mean age of the participants, magnetic field strengths of the scanners and different disorders by using meta-regression and subgroup analysis. In total 52 datasets (N = 1427) were identified and showed significant heterogeneity in the left-right differences and the unilateral volume per se. Moderator analyses suggested that such heterogeneity was mainly due to different MRI scanners and segmentation approaches used. While inversed asymmetry patterns were suggested in patients with depression (leftward) and schizophrenia (rightward), no significant disorder-related differences relative to healthy controls were found in either the left-right asymmetry or the unilateral volume. This study provides useful data for future studies of brain imaging and methodological developments related to precision habenula measurements, and also helps to further understand potential roles of the habenula in various disorders.
Assuntos
Habenula , Humanos , Habenula/diagnóstico por imagem , Cognição , Imageamento por Ressonância Magnética , Lateralidade FuncionalRESUMO
BACKGROUND: The identification of cancer types is of great significance for early diagnosis and clinical treatment of cancer. Clustering cancer samples is an important means to identify cancer types, which has been paid much attention in the field of bioinformatics. The purpose of cancer clustering is to find expression patterns of different cancer types, so that the samples with similar expression patterns can be gathered into the same type. In order to improve the accuracy and reliability of cancer clustering, many clustering methods begin to focus on the integration analysis of cancer multi-omics data. Obviously, the methods based on multi-omics data have more advantages than those using single omics data. However, the high heterogeneity and noise of cancer multi-omics data pose a great challenge to the multi-omics analysis method. RESULTS: In this study, in order to extract more complementary information from cancer multi-omics data for cancer clustering, we propose a low-rank subspace clustering method called multi-view manifold regularized compact low-rank representation (MmCLRR). In MmCLRR, each omics data are regarded as a view, and it learns a consistent subspace representation by imposing a consistence constraint on the low-rank affinity matrix of each view to balance the agreement between different views. Moreover, the manifold regularization and concept factorization are introduced into our method. Relying on the concept factorization, the dictionary can be updated in the learning, which greatly improves the subspace learning ability of low-rank representation. We adopt linearized alternating direction method with adaptive penalty to solve the optimization problem of MmCLRR method. CONCLUSIONS: Finally, we apply MmCLRR into the clustering of cancer samples based on multi-omics data, and the clustering results show that our method outperforms the existing multi-view methods.
Assuntos
Algoritmos , Neoplasias , Análise por Conglomerados , Biologia Computacional , Humanos , Neoplasias/genética , Reprodutibilidade dos TestesRESUMO
Biclustering algorithm is an effective tool for processing gene expression datasets. There are two kinds of data matrices, binary data and non-binary data, which are processed by biclustering method. A binary matrix is usually converted from pre-processed gene expression data, which can effectively reduce the interference from noise and abnormal data, and is then processed using a biclustering algorithm. However, biclustering algorithms of dealing with binary data have a poor balance between running time and performance. In this paper, we propose a new biclustering algorithm called the Adjacency Difference Matrix Binary Biclustering algorithm (AMBB) for dealing with binary data to address the drawback. The AMBB algorithm constructs the adjacency matrix based on the adjacency difference values, and the submatrix obtained by continuously updating the adjacency difference matrix is called a bicluster. The adjacency matrix allows for clustering of gene that undergo similar reactions under different conditions into clusters, which is important for subsequent genes analysis. Meanwhile, experiments on synthetic and real datasets visually demonstrate that the AMBB algorithm has high practicability.
Assuntos
Análise de Dados , Perfilação da Expressão Gênica , Algoritmos , Expressão Gênica , Perfilação da Expressão Gênica/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodosRESUMO
Lateralization is a fundamental characteristic of many behaviors and the organization of the brain, and atypical lateralization has been suggested to be linked to various brain-related disorders such as autism and schizophrenia. Right-handedness is one of the most prominent markers of human behavioural lateralization, yet its neurobiological basis remains to be determined. Here, we present a large-scale analysis of handedness, as measured by self-reported direction of hand preference, and its variability related to brain structural and functional organization in the UK Biobank (N = 36,024). A multivariate machine learning approach with multi-modalities of brain imaging data was adopted, to reveal how well brain imaging features could predict individual's handedness (i.e., right-handedness vs. non-right-handedness) and further identify the top brain signatures that contributed to the prediction. Overall, the results showed a good prediction performance, with an area under the receiver operating characteristic curve (AUROC) score of up to 0.72, driven largely by resting-state functional measures. Virtual lesion analysis and large-scale decoding analysis suggested that the brain networks with the highest importance in the prediction showed functional relevance to hand movement and several higher-level cognitive functions including language, arithmetic, and social interaction. Genetic analyses of contributions of common DNA polymorphisms to the imaging-derived handedness prediction score showed a significant heritability (h2=7.55%, p <0.001) that was similar to and slightly higher than that for the behavioural measure itself (h2=6.74%, p <0.001). The genetic correlation between the two was high (rg=0.71), suggesting that the imaging-derived score could be used as a surrogate in genetic studies where the behavioural measure is not available. This large-scale study using multimodal brain imaging and multivariate machine learning has shed new light on the neural correlates of human handedness.
Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Lateralidade Funcional , Humanos , Aprendizado de Máquina , Imageamento por Ressonância Magnética/métodosRESUMO
The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes.
Assuntos
Córtex Cerebral/anatomia & histologia , Córtex Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética/normas , Neuroimagem/normas , Adolescente , Adulto , Idoso , Espessura Cortical do Cérebro , Conjuntos de Dados como Assunto , Humanos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/normas , Viés de Publicação , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Left-right asymmetry of the human brain is one of its cardinal features, and also a complex, multivariate trait. Decades of research have suggested that brain asymmetry may be altered in psychiatric disorders. However, findings have been inconsistent and often based on small sample sizes. There are also open questions surrounding which structures are asymmetrical on average in the healthy population, and how variability in brain asymmetry relates to basic biological variables such as age and sex. Over the last 4 years, the ENIGMA-Laterality Working Group has published six studies of gray matter morphological asymmetry based on total sample sizes from roughly 3,500 to 17,000 individuals, which were between one and two orders of magnitude larger than those published in previous decades. A population-level mapping of average asymmetry was achieved, including an intriguing fronto-occipital gradient of cortical thickness asymmetry in healthy brains. ENIGMA's multi-dataset approach also supported an empirical illustration of reproducibility of hemispheric differences across datasets. Effect sizes were estimated for gray matter asymmetry based on large, international, samples in relation to age, sex, handedness, and brain volume, as well as for three psychiatric disorders: autism spectrum disorder was associated with subtly reduced asymmetry of cortical thickness at regions spread widely over the cortex; pediatric obsessive-compulsive disorder was associated with altered subcortical asymmetry; major depressive disorder was not significantly associated with changes of asymmetry. Ongoing studies are examining brain asymmetry in other disorders. Moreover, a groundwork has been laid for possibly identifying shared genetic contributions to brain asymmetry and disorders.
Assuntos
Transtorno do Espectro Autista/patologia , Córtex Cerebral/anatomia & histologia , Transtorno Depressivo Maior/patologia , Substância Cinzenta/anatomia & histologia , Imageamento por Ressonância Magnética , Neuroimagem , Transtorno Obsessivo-Compulsivo/patologia , Transtorno do Espectro Autista/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Humanos , Estudos Multicêntricos como Assunto , Transtorno Obsessivo-Compulsivo/diagnóstico por imagemRESUMO
Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive-compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.
Assuntos
Neuroimagem , Transtorno Obsessivo-Compulsivo , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Humanos , Aprendizado de Máquina , Estudos Multicêntricos como Assunto , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/patologiaRESUMO
The human cerebral hemispheres show a left-right asymmetrical torque pattern, which has been claimed to be absent in chimpanzees. The functional significance and developmental mechanisms are unknown. Here, we carried out the largest-ever analysis of global brain shape asymmetry in magnetic resonance imaging data. Three population datasets were used, UK Biobank (N = 39 678), Human Connectome Project (N = 1113), and BIL&GIN (N = 453). At the population level, there was an anterior and dorsal skew of the right hemisphere, relative to the left. Both skews were associated independently with handedness, and various regional gray and white matter metrics oppositely in the two hemispheres, as well as other variables related to cognitive functions, sociodemographic factors, and physical and mental health. The two skews showed single nucleotide polymorphisms-based heritabilities of 4-13%, but also substantial polygenicity in causal mixture model analysis, and no individually significant loci were found in genome-wide association studies for either skew. There was evidence for a significant genetic correlation between horizontal brain skew and autism, which requires future replication. These results provide the first large-scale description of population-average brain skews and their inter-individual variations, their replicable associations with handedness, and insights into biological and other factors which associate with human brain asymmetry.
Assuntos
Encéfalo/fisiologia , Lateralidade Funcional/genética , Genômica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Lateralidade Funcional/fisiologia , Genótipo , Substância Cinzenta/diagnóstico por imagem , Nível de Saúde , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Fatores Sociodemográficos , Substância Branca/diagnóstico por imagemRESUMO
Many microRNAs (miRNAs) have been confirmed to be associated with the generation of human diseases. Capturing miRNA-disease associations (M-DAs) provides an effective way to understand the etiology of diseases. Many models for predicting M-DAs have been constructed; nevertheless, there are still several limitations, such as generally considering direct information between miRNAs and diseases, usually ignoring potential knowledge hidden in isolated miRNAs or diseases. To overcome these limitations, in this study a novel method for predicting M-DAs was developed named TLNPMD, highlights of which are the introduction of drug heuristic information and a bipartite network reconstruction strategy. Specifically, three bipartite networks, including drug-miRNA, drug-disease, and miRNA-disease, were reconstructed as weighted ones using such reconstruction strategy. Based on these weighted bipartite networks, as well as three corresponding similarity networks of drugs, miRNAs and diseases, the miRNA-drug-disease three-layer heterogeneous network was constructed. Then, this heterogeneous network was converted into three two-layer heterogeneous networks, for each of which the network path computational model was employed to predict association scores. Finally, both direct and indirect miRNA-disease paths were used to predict M-DAs. Comparative experiments of TLNPMD and other four models were performed and evaluated by five-fold and global leave-one-out cross validations, results of which show that TLNPMD has the highest AUC values among those of compared methods. In addition, case studies of two common diseases were carried out to validate the effectiveness of the TLNPMD. These experiments demonstrate that the TLNPMD may serve as a promising alternative to existing methods for predicting M-DAs.
Assuntos
MicroRNAs , Algoritmos , Biologia Computacional/métodos , Humanos , MicroRNAs/genéticaRESUMO
Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.
Assuntos
Córtex Cerebral/diagnóstico por imagem , Neuroimagem/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: MicroRNAs (miRNAs) are non-coding RNAs with regulatory functions. Many studies have shown that miRNAs are closely associated with human diseases. Among the methods to explore the relationship between the miRNA and the disease, traditional methods are time-consuming and the accuracy needs to be improved. In view of the shortcoming of previous models, a method, collaborative matrix factorization based on matrix completion (MCCMF) is proposed to predict the unknown miRNA-disease associations. RESULTS: The complete matrix of the miRNA and the disease is obtained by matrix completion. Moreover, Gaussian Interaction Profile kernel is added to the miRNA functional similarity matrix and the disease semantic similarity matrix. Then the Weight K Nearest Known Neighbors method is used to pretreat the association matrix, so the model is close to the reality. Finally, collaborative matrix factorization method is applied to obtain the prediction results. Therefore, the MCCMF obtains a satisfactory result in the fivefold cross-validation, with an AUC of 0.9569 (0.0005). CONCLUSIONS: The AUC value of MCCMF is higher than other advanced methods in the fivefold cross validation experiment. In order to comprehensively evaluate the performance of MCCMF, accuracy, precision, recall and f-measure are also added. The final experimental results demonstrate that MCCMF outperforms other methods in predicting miRNA-disease associations. In the end, the effectiveness and practicability of MCCMF are further verified by researching three specific diseases.
Assuntos
Algoritmos , Predisposição Genética para Doença , MicroRNAs/genética , Área Sob a Curva , Redes Reguladoras de Genes , Hepatoblastoma/genética , Humanos , Curva ROC , Reprodutibilidade dos Testes , Retinoblastoma/genética , Fatores de RiscoRESUMO
Differentially expressed genes selection becomes a hotspot and difficulty in recent molecular biology. Low-rank representation (LRR) uniting graph Laplacian regularization has gained good achievement in the above field. However, the co-expression information of data cannot be captured well by graph regularization. Therefore, a novel low-rank representation method regularized by dual-hypergraph Laplacian is proposed to reveal the intrinsic geometrical structures hidden in the samples and genes direction simultaneously, which is called dual-hypergraph Laplacian regularized LRR (DHLRR). Finally, a low-rank matrix and a sparse perturbation matrix can be recovered from genomic data by DHLRR. Based on the sparsity of differentially expressed genes, the sparse disturbance matrix can be applied to extracting differentially expressed genes. In our experiments, two gene analysis tools are used to discuss the experimental results. The results on two real genomic data and an integrated dataset prove that DHLRR is efficient and effective in finding differentially expressed genes.
Assuntos
Regulação Neoplásica da Expressão Gênica , Genômica/métodos , Neoplasias Pancreáticas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , HumanosRESUMO
BACKGROUND: Identifying different types of cancer based on gene expression data has become hotspot in bioinformatics research. Clustering cancer gene expression data from multiple cancers to their own class is a significance solution. However, the characteristics of high-dimensional and small samples of gene expression data and the noise of the data make data mining and research difficult. Although there are many effective and feasible methods to deal with this problem, the possibility remains that these methods are flawed. RESULTS: In this paper, we propose the graph regularized low-rank representation under symmetric and sparse constraints (sgLRR) method in which we introduce graph regularization based on manifold learning and symmetric sparse constraints into the traditional low-rank representation (LRR). For the sgLRR method, by means of symmetric constraint and sparse constraint, the effect of raw data noise on low-rank representation is alleviated. Further, sgLRR method preserves the important intrinsic local geometrical structures of the raw data by introducing graph regularization. We apply this method to cluster multi-cancer samples based on gene expression data, which improves the clustering quality. First, the gene expression data are decomposed by sgLRR method. And, a lowest rank representation matrix is obtained, which is symmetric and sparse. Then, an affinity matrix is constructed to perform the multi-cancer sample clustering by using a spectral clustering algorithm, i.e., normalized cuts (Ncuts). Finally, the multi-cancer samples clustering is completed. CONCLUSIONS: A series of comparative experiments demonstrate that the sgLRR method based on low rank representation has a great advantage and remarkable performance in the clustering of multi-cancer samples.
Assuntos
Algoritmos , Neoplasias/genética , Análise por Conglomerados , Mineração de Dados , Bases de Dados Genéticas , Humanos , Redução Dimensional com Múltiplos Fatores , OncogenesRESUMO
Spatial navigation is a crucial ability for living. Previous animal studies have shown that the S100B gene is causally related to spatial navigation performance in mice. However, the genetic factors influencing human navigation and its neural substrates remain unclear. Here, we provided the first evidence that the S100B gene modulates neural processing of navigationally relevant scenes in humans. First, with a novel protocol, we demonstrated that the spatial pattern of S100B gene expression in postmortem brains was associated with brain activation pattern for spatial navigation in general, and for scene processing in particular. Further, in a large fMRI cohort of healthy adults of Han Chinese (N = 202), we found that S100B gene polymorphisms modulated scene selectivity in the retrosplenial cortex (RSC) and parahippocampal place area. Finally, the serum levels of S100B protein mediated the association between S100B gene polymorphism and scene selectivity in the RSC. Our study takes the first step toward understanding the neurogenetic mechanism of human spatial navigation and suggests a novel approach to discover candidate genes modulating cognitive functions.
Assuntos
Povo Asiático/genética , Encéfalo/fisiologia , Córtex Cerebral/fisiologia , Giro Para-Hipocampal/fisiologia , Subunidade beta da Proteína Ligante de Cálcio S100/genética , Percepção Espacial/fisiologia , Adolescente , Adulto , Mapeamento Encefálico/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Reconhecimento Visual de Modelos/fisiologia , Navegação Espacial/fisiologia , Adulto JovemRESUMO
Spatial navigation is a crucial ability for living. Previous studies have shown that males are better at navigation than females, but little is known about the neural basis underlying the sex differences. In this study, we investigated whether cortical scene processing in three well-established scene-selective regions was sexually different, by examining sex differences in scene selectivity and its behavioral relevance to navigation. To do this, we used functional magnetic resonance imaging (fMRI) to scan the parahippocampal place area (PPA), retrosplenial complex (RSC), and occipital place area (OPA) in a large cohort of healthy young adults viewing navigationally relevant scenes (N = 202), and correlated their neural selectivity to scenes with their self-reported navigational ability. Behaviorally, we replicated the previous finding that males were better at navigation than females. Neurally, we found that the scene selectivity in the bilateral PPA, not in the RSC or OPA, was significantly higher in males than females. Such differences could not be explained by confounding factors including brain size and fMRI data quality. Importantly, males, not females, with stronger scene selectivity in the left PPA possessed better navigational ability. This brain-behavior association could not be accounted for by non-navigational abilities (i.e., intelligence and mental rotation ability). Overall, our study provides novel empirical evidence demonstrating sex differences in the brain activity, inviting further studies on sex differences in the neural network for spatial navigation.
Assuntos
Encéfalo/fisiologia , Caracteres Sexuais , Navegação Espacial/fisiologia , Mapeamento Encefálico/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
Scene-selective regions (SSRs), including the parahippocampal place area (PPA), retrosplenial cortex (RSC), and transverse occipital sulcus (TOS), are among the most widely characterized functional regions in the human brain. However, previous studies have mostly focused on the commonality within each SSR, providing little information on different aspects of their variability. In a large group of healthy adults (N = 202), we used functional magnetic resonance imaging to investigate different aspects of topographical and functional variability within SSRs, including interindividual, interhemispheric, and sex differences. First, the PPA, RSC, and TOS were delineated manually for each individual. We then demonstrated that SSRs showed substantial interindividual variability in both spatial topography and functional selectivity. We further identified consistent interhemispheric differences in the spatial topography of all three SSRs, but distinct interhemispheric differences in scene selectivity. Moreover, we found that all three SSRs showed stronger scene selectivity in men than in women. In summary, our work thoroughly characterized the interindividual, interhemispheric, and sex variability of the SSRs and invites future work on the origin and functional significance of these variabilities. Additionally, we constructed the first probabilistic atlases for the SSRs, which provide the detailed anatomical reference for further investigations of the scene network. Hum Brain Mapp 38:2260-2275, 2017. © 2017 Wiley Periodicals, Inc.
Assuntos
Mapeamento Encefálico , Córtex Cerebral/fisiologia , Individualidade , Caracteres Sexuais , Percepção Espacial/fisiologia , Adolescente , Córtex Cerebral/diagnóstico por imagem , Feminino , Lateralidade Funcional/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangue , Adulto JovemRESUMO
BACKGROUND Polymorphisms of the endothelial nitric oxide synthase (eNOS) gene are reportedly associated with myocardial infarction (MI) risk. However, definitive evidence of this association is lacking. In this study, we investigated the potential association of eNOS gene polymorphisms with MI risk by conducting a meta-analysis of studies evaluating this association. MATERIAL AND METHODS PubMed, Web of Knowledge, ScienceDirect, China National Knowledge Infrastructure (CNKI), WanFang, and Database of Chinese Scientific and Technical Periodicals (VIP) were searched for relevant studies. Pooled odds ratios (OR) with 95% confidence interval (CI) were calculated to evaluate the association of eNOS gene T-786C and 4b4a polymorphisms with MI risk. RESULTS Fifteen studies with 8,067 controls and 4,923 MI cases were included in the final meta-analysis. In the overall analysis, T-786C (rs2070744) polymorphism was associated with MI risk (p<0.05, OR=1.69, 95% CI: 1.53-1.86 for T vs. C; p<0.05, OR=2.76, 95% CI: 2.03-3.75 for TT vs. CC; p<0.05, OR=1.74, 95% CI 1.56-1.95 for TT vs. (CT + CC); p<0.05, OR=2.43, 95% CI: 1.79-3.30 for (CT + TT) vs. CC). In addition, a significant association between 4b4a VNTR polymorphism and MI risk was observed. On sub-group analyses by ethnicity, a significant increase in MI risk was observed separately for Asian and Caucasian populations for T-786C polymorphism, but not for the 4b4a polymorphism. CONCLUSIONS In this meta-analysis, T-786C polymorphism of the eNOS gene was associated with the risk of MI, especially in the Asian populations.
Assuntos
Infarto do Miocárdio/genética , Óxido Nítrico Sintase Tipo III/genética , Povo Asiático/genética , Células Endoteliais/patologia , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Repetições Minissatélites , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Óxido Nítrico Sintase Tipo III/metabolismo , Polimorfismo de Nucleotídeo Único , Fatores de Risco , População Branca/genéticaRESUMO
As with miRNAs a decade ago, long non-coding RNAs (lncRNAs) are emerging as a new class of RNAs involved in physiological and pathological processes. Recent evidences have shown that lncRNAs play a role in cancer metabolism. The relationship between lncRNAs and aerobic glycolysis provides new strategies for the treatment of cancer. Here we discuss recent findings on the role of lncRNAs in aerobic glycolysis and provide insights into their mechanisms of action. In addition, we explore the potential challenges in using lncRNAs as targets for cancer therapy.
Assuntos
Regulação Neoplásica da Expressão Gênica , Glicólise/genética , Neoplasias/genética , RNA Longo não Codificante/genética , Animais , Linhagem Celular Tumoral , Humanos , Terapia de Alvo Molecular/métodos , Neoplasias/metabolismo , Neoplasias/terapia , Transdução de Sinais/genéticaRESUMO
Face-selective regions (FSRs) are among the most widely studied functional regions in the human brain. However, individual variability of the FSRs has not been well quantified. Here we use functional magnetic resonance imaging (fMRI) to localize the FSRs and quantify their spatial and functional variabilities in 202 healthy adults. The occipital face area (OFA), posterior and anterior fusiform face areas (pFFA and aFFA), posterior continuation of the superior temporal sulcus (pcSTS), and posterior and anterior STS (pSTS and aSTS) were delineated for each individual with a semi-automated procedure. A probabilistic atlas was constructed to characterize their interindividual variability, revealing that the FSRs were highly variable in location and extent across subjects. The variability of FSRs was further quantified on both functional (i.e., face selectivity) and spatial (i.e., volume, location of peak activation, and anatomical location) features. Considerable interindividual variability and rightward asymmetry were found in all FSRs on these features. Taken together, our work presents the first effort to characterize comprehensively the variability of FSRs in a large sample of healthy subjects, and invites future work on the origin of the variability and its relation to individual differences in behavioral performance. Moreover, the probabilistic functional atlas will provide an adequate spatial reference for mapping the face network.