RESUMO
There have been a number of reports about the transcriptional regulatory networks in schizophrenia. However, most of these studies were based on a specific transcription factor or a single dataset, an approach that is inadequate to understand the diverse etiology and underlying common characteristics of schizophrenia. Here we reconstructed and compared the transcriptional regulatory network for lipid metabolism enzymes using 15 public transcriptome datasets of neural cells from schizophrenia patients. Since many of the well-known schizophrenia-related SNPs are in enhancers, we reconstructed a network including enhancer-dependent regulation and found that 53.3 % of the total number of edges (7,577 pairs) involved regulation via enhancers. By examining multiple datasets, we found common and unique transcriptional modes of regulation. Furthermore, enrichment analysis of SNPs that were connected with genes in the transcriptional regulatory networks by eQTL suggested an association with hematological cell counts and some other traits/diseases, whose relationship to schizophrenia was either not or insufficiently reported in previous studies. Based on these results, we suggest that in future studies on schizophrenia, information on genotype, comorbidities and hematological cell counts should be included, along with the transcriptome, for a more detailed genetic stratification and mechanistic exploration of schizophrenia.
Assuntos
Esquizofrenia , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Metabolismo dos Lipídeos/genética , Esquizofrenia/genéticaRESUMO
Influenza viruses are a major public health problem. Vaccines are the best available countermeasure to induce effective immunity against infection with seasonal influenza viruses; however, the breadth of antibody responses in infection versus vaccination is quite different. Here, we show that nasal infection controls two sequential processes to induce neutralizing IgG antibodies recognizing the hemagglutinin (HA) of heterotypic strains. The first is viral replication in the lung, which facilitates exposure of shared epitopes that are otherwise hidden from the immune system. The second process is the germinal center (GC) response, in particular, IL-4 derived from follicular helper T cells has an essential role in the expansion of rare GC-B cells recognizing the shared epitopes. Therefore, the combination of exposure of the shared epitopes and efficient proliferation of GC-B cells is critical for generating broadly-protective antibodies. These observations provide insight into mechanisms promoting broad protection from virus infection.
Assuntos
Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , Hemaglutininas Virais/imunologia , Interleucina-4/imunologia , Infecções por Orthomyxoviridae/imunologia , Animais , Anticorpos Antivirais/sangue , Anticorpos Amplamente Neutralizantes/sangue , Epitopos/imunologia , Feminino , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H2N2/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais/imunologia , Células T Auxiliares Foliculares/imunologia , VacinaçãoRESUMO
Halomonas axialensis is a halophilic bacterial species discovered near a deep-sea hydrothermal vent. Here, we report the first single closed genome sequence of the original strain, Halomonas axialensis strain Althf1. The genome was assembled by Nanopore sequencing and consisted of a single chromosome of 3.6 Mbp with 56.8% G+C content.