Coordination among cortical neurons is believed to be a key element in mediating many high-level cortical processes such as perception, attention, learning, and memory formation. Inferring the structure of the neural circuitry underlying this coordination is important to characterize the highly nonlinear, time-varying interactions between cortical neurons in the presence of complex stimuli. In this work, we investigate the applicability of dynamic Bayesian networks (DBNs) in inferring the effective connectivity between spiking cortical neurons from their observed spike trains. We demonstrate that DBNs can infer the underlying nonlinear and time-varying causal interactions between these neurons and can discriminate between mono- and polysynaptic links between them under certain constraints governing their putative connectivity. We analyzed conditionally Poisson spike train data mimicking spiking activity of cortical networks of small and moderately large size. The performance was assessed and compared to other methods under systematic variations of the network structure to mimic a wide range of responses typically observed in the cortex. Results demonstrate the utility of DBN in inferring the effective connectivity in cortical networks.
Introduction Recent technological advances in microfabrication of high-density multi-electrode arrays (MEA) permitted simultaneous recording of a few hundreds of neurons, and thus paved the way to investigate the dynamics of distributed neural circuits. Identifying functional connectivity between these simultaneously recorded neurons is important to understand how the brain orchestrates information processing when performing complex motor tasks.
Thymomas and thymic carcinomas are malignant thymic epithelial tumors (TETs) with poor outcomes if non-resectable. However, the tumorigenesis, especially the metabolic mechanisms involved, is poorly studied. Untargeted metabolomics analysis was utilized to screen for differential metabolic profiles between thymic cancerous tissues and adjunct noncancerous tissues. Combined with transcriptomic data, we comprehensively evaluated the metabolic patterns of TETs. Metabolic scores were constructed to quantify the metabolic patterns of individual tumors. Subsequent investigation of distinct clinical outcomes and the immune landscape associated with the metabolic scores was conducted. Two distinct metabolic patterns and differential metabolic scores were identified between TETs, which were enriched in a variety of biological pathways and correlated with clinical outcomes. In particular, a high metabolic score was highly associated with poorer survival outcomes and immunosuppressive status. More importantly, the expression of two prognostic genes (ASNS and BLVRA) identified from differential metabolism-related genes was significantly associated with patient survival and may play a key role in the tumorigenesis of TETs. Our findings suggest that differential metabolic patterns in TETs are relevant to tumorigenesis and clinical outcome. Specific transcriptomic alterations in differential metabolism-related genes may serve as predictive biomarkers of survival outcomes and potential targets for the treatment of patients with TETs.
Abstract Background Vasa is a member of the DEAD-box protein family that plays an indispensable role in mammalian spermatogenesis, particularly during meiosis. Bovine vasa homology ( Bvh ) of Bos taurus has been reported, however, its function in bovine testicular tissue remains obscure. This study aimed to reveal the functions of Bvh and to determine whether Bvh is a candidate gene in the regulation of spermatogenesis in bovine, and to illustrate whether its transcription is regulated by alternative splicing and DNA methylation. Results Here we report the molecular characterization, alternative splicing pattern, expression and promoter methylation status of Bvh . The full-length coding region of Bvh was 2190 bp, which encodes a 729 amino acid (aa) protein containing nine consensus regions of the DEAD box protein family. Bvh is expressed only in the ovary and testis of adult cattle. Two splice variants were identified and termed Bvh - V4 (2112 bp and 703 aa) and Bvh - V45 (2040 bp and 679 aa). In male cattle, full-length Bvh ( Bvh - FL ), Bvh - V4 and Bvh - V45 are exclusively expressed in the testes in the ratio of 2.2:1.6:1, respectively. Real-time PCR revealed significantly reduced mRNA expression of Bvh - FL , Bvh - V4 and Bvh - V45 in testes of cattle-yak hybrids, with meiotic arrest compared with cattle and yaks with normal spermatogenesis (P < 0.01). The promoter methylation level of Bvh in the testes of cattle-yak hybrids was significantly greater than in cattle and yaks (P < 0.01). Conclusion In the present study, Bvh was isolated and characterized. These data suggest that Bvh functions in bovine spermatogenesis, and that transcription of the gene in testes were regulated by alternative splice and promoter methylation.
Abstract Due to their sessile nature, plants must respond to various environmental assaults in a coordinated manner. The endoplasmic reticulum is a central hub for plant responses to various stresses. We previously showed that Phytophthora utilizes effector PsAvh262-mediated binding immunoglobulin protein (BiP) accumulation for suppressing endoplasmic reticulum stress-triggered cell death. As a BiP binding partner, Bcl-2-associated athanogene 7 (BAG7) plays a crucial role in the maintenance of the unfolded protein response, but little is known about its role in plant immunity. In this work, we reveal a double-faced role of BAG7 in Arabidopsis–Phytophthora interaction in which it regulates endoplasmic reticulum stress-mediated immunity oppositely in different cellular compartments. In detail, it acts as a susceptibility factor in the endoplasmic reticulum, but plays a resistance role in the nucleus against Phytophthora. Phytophthora infection triggers the endoplasmic reticulum-to-nucleus translocation of BAG7, the same as abiotic heat stress; however, this process can be prevented by PsAvh262-mediated BiP accumulation. Moreover, the immunoglobulin/albumin-binding domain in PsAvh262 is essential for both pathogen virulence and BiP accumulation. Taken together, our study uncovers a double-faced role of BAG7; Phytophthora advances its colonization in planta by utilizing an effector to detain BAG7 in the endoplasmic reticulum.
Maize (Zea mays) is a major staple crop. Maize kernel size and weight are important contributors to its yield. Here, we measured kernel length, kernel width, kernel thickness, hundred kernel weight, and kernel test weight in 10 recombinant inbred line populations and dissected their genetic architecture using three statistical models. In total, 729 quantitative trait loci (QTLs) were identified, many of which were identified in all three models, including 22 major QTLs that each can explain more than 10% of phenotypic variation. To provide candidate genes for these QTLs, we identified 30 maize genes that are orthologs of 18 rice (Oryza sativa) genes reported to affect rice seed size or weight. Interestingly, 24 of these 30 genes are located in the identified QTLs or within 1 Mb of the significant single-nucleotide polymorphisms. We further confirmed the effects of five genes on maize kernel size/weight in an independent association mapping panel with 540 lines by candidate gene association analysis. Lastly, the function of ZmINCW1, a homolog of rice GRAIN INCOMPLETE FILLING1 that affects seed size and weight, was characterized in detail. ZmINCW1 is close to QTL peaks for kernel size/weight (less than 1 Mb) and contains significant single-nucleotide polymorphisms affecting kernel size/weight in the association panel. Overexpression of this gene can rescue the reduced weight of the Arabidopsis (Arabidopsis thaliana) homozygous mutant line in the AtcwINV2 gene (Arabidopsis ortholog of ZmINCW1). These results indicate that the molecular mechanisms affecting seed development are conserved in maize, rice, and possibly Arabidopsis.
To investigate the effect of an adenovirus vector containing murine interleukin-21 gene (Ad-GFP-mIL-21) in virus clearance and on the production of HBV-specific antibodies in mice with persistent HBV infection.ELISA and Western blot analysis were used to detect the expression of mIL-21 in the supernatant and cytoplasm of cultured HepG2.2.15 cells after infection by Ad-GFP-mIL-21. Mouse models of chronic HBV infection established by in vivo transduction with rAAV8-1.3HBV were divided into 3 groups for treatment 12 weeks later with injection of Ad-GFP-mIL-21, GFP recombinant adenovirus or PBS via the tail vein. Serum levels of HBsAg, HBsAb, HBcAb, and mIL-21 in the mice were detected using ELISA, and the expression of Ad-GFP-mIL-21 in the organs was observed by fluorescent microscopy at different time points after the injection.Ad-GFP-mIL-21 was capable of infecting HepG2.2.15 cells in vitro, and the levels of mIL-21 in the supernatant were correlated with the titers of adenovirus administered and the infection time. In the mice with persistent HBV infection, green fluorescence expression was observed almost exclusively in the liver on day 4 after injection of Ad-GFP-mIL21, and serum levels of IL-21 increased significantly compared with the level before treatment (P<0.05). Although HBsAb was undetectable in both Ad-GFP-mIL21-injected and control mice on day 13, a significantly higher serum level of HBcAb was detected in the mice with Ad-GFP-mIL21 injection (P<0.05).Ad-GFP-mIL-21 can efficiently express mIL-21 in mice with chronic HBV infection to downregulate serum levels of HBsAg and promote HBcAb production, suggesting its efficacy in controlling chronic HBV infection.
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