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Background: The mechanism of winter survival for perennials involves multiple levels of gene regulation, especially cold resistance. Agropyron mongolicum is one important perennial grass species, but there is little information regarding its overwintering mechanism. We performed a comprehensive transcriptomics study to evaluate global gene expression profiles regarding the winter survival of Agropyron mongolicum. A genome-wide gene expression analysis involving four different periods was identified. Twenty-eight coexpression modules with distinct patterns were performed for transcriptome profiling. Furthermore, differentially expressed genes (DEGs) and their functional characterization were defined using a genome database such as NT, NR, COG, and KEGG. Result: A total of 79.6% of the unigenes were characterized to be involved in 136 metabolic pathways. In addition, the expression level of ABA receptor genes, regulation of transcription factors, and a coexpression network analysis were conducted using transcriptome data. We found that ABA receptors regulated downstream gene expression by activating bZIP and NAC transcription factors to improve cold resistance and winter survival. Conclusion: This study provides comprehensive transcriptome data for the characterization of overwintering-related gene expression profiles in A. mongolicum. Genomics resources can help provide a better understanding of the overwintering mechanism for perennial gramineae species. By analyzing genome-wide expression patterns for the four key stages of tiller bud development, the functional characteristics of the DEGs were identified that participated in various metabolic pathways and have been shown to be strongly associated with cold tolerance. These results can be further exploited to determine the mechanism of overwintering in perennial gramineae species. [ABSTRACT FROM AUTHOR]

For pyruvate-producing strains, intracellular reduced nicotinamide adenine dinucleotide ( NADH) accumulation is the main reason for the glycolysis inhibition. Comparing with glucose, using sodium gluconate as carbon source brought a decrease in NADH production and an increase in pyruvate production in engineered strain YP211. In order to explore the metabolic advantages of gluconate, genome-wide transcriptome analysis was employed to compare the metabolic differences between the two carbon sources. The results showed that the transcription of the genes gntU, gntK, and gntT responsible for transport and phosphorylation of gluconate, and genes edd and eda belonging to the Entner-Doudoroff ( ED) pathway, was significantly enhanced. This suggested that the shortest route for the synthesis of pyruvate from gluconate was activated, and the synthesis of NADH was halved. Besides, the transcription of genes glp ABCDTKF related to the glycerol metabolism was significantly enhanced, which might be because glycerol metabolism pathways were activated in the absence of glucose. These results provided valuable information for the further design of metabolic pathways in the construction of pyruvate-producing strains. Significance and Impact of the Study Comparing with glucose, using sodium gluconate as carbon source brought a decrease in nicotinamide adenine dinucleotide and an increase in pyruvate production in engineered strain YP211. From the genome-wide transcriptome analysis, the Entner-Doudoroff pathway was activated strongly in gluconate metabolism, which innovatively provided a shorter and more effective pathway for pyruvate production. [ABSTRACT FROM AUTHOR]

Background Cryptococcus neoformans is the most common cause of fungal meningitis among individuals with HIV/AIDS, which is uniformly fatal without proper treatment. The underlying mechanism of disease development in the brain that leads to cryptococcal meningoencephalitis remains incompletely understood. We have previously demonstrated that inositol transporters (ITR) are required for Cryptococcus virulence. The itr1aΔ itr3cΔ double mutant of C. neoformans was attenuated for virulence in a murine model of intracerebral infection; demonstrating that Itr1a and Itr3c are required for full virulence during brain infection, despite a similar growth rate between the mutant and wild type strains in the infected brain. Results To understand the immune pathology associated with infection by the itr1aΔ itr3cΔ double mutant, we investigated the molecular correlates of host immune response during mouse brain infection. We used genome-wide transcriptome shotgun sequencing (RNA-Seq) and quantitative real-time PCR (qRT-PCR) methods to examine the host gene expression profile in the infected brain. Our results show that compared to the wild type, infection of mouse brains by the mutant leads to significant activation of cellular networks/pathways associated with host protective immunity. Most of the significantly differentially expressed genes (SDEG) are part of immune cell networks such as tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) regulon, indicating that infection by the mutant mounts a stronger host immune response compared to the wild type. Interestingly, a significant reduction in glucuronoxylomannan (GXM) secretion was observed in the itr1aΔ itr3cΔ mutant cells, indicating that inositol utilization pathways play a role in capsule production. Conclusions Since capsule has been shown to impact the host response during Cryptococcus-host interactions, our results suggest that the reduced GXM production may contribute to the increased immune activation in the mutant-infected animals. [ABSTRACT FROM AUTHOR]

The paper presents a formalized statement of the problem of selecting parameters and construction of a genomic classifier for medical test systems with mathematical methods of machine learning without the use of biological and medical knowledge. A method is proposed to solve this problem. The results of testing the method using microarray datasets containing information on genome-wide transcriptome of the samples of estrogen positive breast tumors are discussed. Testing showed that the quality of classification provided by the constructed test system and implemented on the basis of assessments of expression of 12 genes is not inferior to the quality of classification carried out by such test systems as OncotypeDX and MammaPrint. [ABSTRACT FROM AUTHOR]

Background: Infection of humans with Mycobacterium tuberculosis (Mtb) results in latent tuberculosis infection (LTBI) in 90-95% of immune competent individuals, with no symptoms of active disease. The World Health Organization estimates that 1.5 billion people have LTBI, which can reactivate in the setting of waning host immunity, posing a threat to global TB control. Various animal models have been used to study the pathogenesis of TB. However, besides nonhuman primates, rabbits are the only animal model that fully recapitulates the pathological features of human TB, including progressive disease with necrosis and cavitation or establishment of spontaneous latency. Results: We defined the molecular immunological correlates of LTBI establishment in a rabbit model of pulmonary infection with Mtb CDC1551. After aerosol infection, exponential bacterial growth was noted in the lungs for 4 weeks, followed by a significant decline by 12 weeks, resulting in the absence of cultivable bacilli by 24 weeks. We used rabbit whole genome microarrays to profile the lung transcriptome during the course of infection. At 2 weeks post-infection, gene networks involved in natural killer (NK) and dendritic cell (DC) activation and macrophage antimicrobial activities were highly upregulated. This was followed by upregulation of gene networks involved in macrophage and T cell activation and autophagy, peaking at 4 to 8 weeks. Concomitantly, host Th1, but not Th2 or inflammatory, immune response genes were significantly upregulated. Thus, the expression kinetics of genes involved in cross-talk between innate and adaptive immunity over the first 8 weeks post-infection were consistent with early efficient control of infection in the lungs. Interestingly, expression of many genes of the host innate and adaptive immune response pathways was downregulated at 12 weeks, suggesting that immune activation did not persist once bacilli began to clear from the infected lungs. Conclusions: Our results suggest that early activation of host innate immunity prior to efficient activation of T cellmediated adaptive immunity but not inflammation is essential for establishment of LTBI in Mtb CDC1551-infected rabbits. We also show that T cell activation and the host adaptive immune response networks are dampened once bacterial growth is controlled, ultimately resulting in spontaneous LTBI. [ABSTRACT FROM AUTHOR]