scholarly journals Identification and characterization of novel infection associated transcripts in macrophages

2021 ◽  
Author(s):  
Prabhakar Arumugam ◽  
Rakesh Lodha ◽  
vivek Rao

Regulated expression of genes in response to internal and external stimuli is primarily responsible for the enormous plasticity and robustness of biological systems. Recent studies have elucidated complex regulatory non protein coding transcript (lncRNA) circuits in coordinated response of immune cells. By analysis of lncRNA expression profiles of macrophages in response to Mtb infection, we identified novel highly expressed transcripts, unique in encompassing one functional protein coding transcript- CMPK2 and a previously identified type I IFN responsive lncRNA- NRIR. While these RNA are induced by virulent Mtb early, the complete absence of expression in non-viable Mtb infected cells coupled to a more protracted expression profile in the case of BCG suggest an important role in macrophage response to mycobacteria. Moreover, enhanced expression was observed in macrophages from TB patients. The elevated expression by 1h in response to fast growing bacteria further emphasizes the importance of these RNAs in the macrophage infection response. These transcripts (TILT1, 2,3 - TLR4 and Infection induced Long Transcript) are triggered exclusively by TLR4 stimulation (LPS) with faster and stronger kinetics in comparison to the lncRNA–NRIR. Overall, we provide evidence for the presence of numerous transcripts that is a part of the early infection response program of macrophages.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
M. Korabecna ◽  
A. Zinkova ◽  
I. Brynychova ◽  
B. Chylikova ◽  
P. Prikryl ◽  
...  

Abstract The cell-free DNA (cfDNA) is always present in plasma, and it is biomarker of growing interest in prenatal diagnostics as well as in oncology and transplantology for therapy efficiency monitoring. But does this cfDNA have a physiological role? Here we show that cfDNA presence and clearance in plasma of healthy individuals plays an indispensable role in immune system regulation. We exposed THP1 cells to healthy individuals’ plasma with (NP) and without (TP) cfDNA. In cells treated with NP, we found elevated expression of genes whose products maintain immune system homeostasis. Exposure of cells to TP triggered an innate immune response (IIR), documented particularly by elevated expression of pro-inflammatory interleukin 8. The results of mass spectrometry showed a higher abundance of proteins associated with IIR activation due to the regulation of complement cascade in cells cultivated with TP. These expression profiles provide evidence that the presence of cfDNA and its clearance in plasma of healthy individuals regulate fundamental mechanisms of the inflammation process and tissue homeostasis. The detailed understanding how neutrophil extracellular traps and their naturally occurring degradation products affect the performance of immune system is of crucial interest for future medical applications.


2011 ◽  
Vol 81 (1) ◽  
pp. 34-42 ◽  
Author(s):  
Joel Deneau ◽  
Taufeeq Ahmed ◽  
Roger Blotsky ◽  
Krzysztof Bojanowski

Type II diabetes is a metabolic disease mediated through multiple molecular pathways. Here, we report anti-diabetic effect of a standardized isolate from a fossil material - a mineraloid leonardite - in in vitro tests and in genetically diabetic mice. The mineraloid isolate stimulated mitochondrial metabolism in human fibroblasts and this stimulation correlated with enhanced expression of genes coding for mitochondrial proteins such as ATP synthases and ribosomal protein precursors, as measured by DNA microarrays. In the diabetic animal model, consumption of the Totala isolate resulted in decreased weight gain, blood glucose, and glycated hemoglobin. To our best knowledge, this is the first description ever of a fossil material having anti-diabetic activity in pre-clinical models.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Maria Pujantell ◽  
Roger Badia ◽  
Iván Galván-Femenía ◽  
Edurne Garcia-Vidal ◽  
Rafael de Cid ◽  
...  

AbstractInfection by human papillomavirus (HPV) alters the microenvironment of keratinocytes as a mechanism to evade the immune system. A-to-I editing by ADAR1 has been reported to regulate innate immunity in response to viral infections. Here, we evaluated the role of ADAR1 in HPV infection in vitro and in vivo. Innate immune activation was characterized in human keratinocyte cell lines constitutively infected or not with HPV. ADAR1 knockdown induced an innate immune response through enhanced expression of RIG-I-like receptors (RLR) signaling cascade, over-production of type-I IFNs and pro-inflammatory cytokines. ADAR1 knockdown enhanced expression of HPV proteins, a process dependent on innate immune function as no A-to-I editing could be identified in HPV transcripts. A genetic association study was performed in a cohort of HPV/HIV infected individuals followed for a median of 6 years (range 0.1–24). We identified the low frequency haplotype AACCAT significantly associated with recurrent HPV dysplasia, suggesting a role of ADAR1 in the outcome of HPV infection in HIV+ individuals. In summary, our results suggest that ADAR1-mediated innate immune activation may influence HPV disease outcome, therefore indicating that modification of innate immune effectors regulated by ADAR1 could be a therapeutic strategy against HPV infection.


Author(s):  
Denis Bienroth ◽  
Hieu T. Nim ◽  
Dimitar Garkov ◽  
Karsten Klein ◽  
Sabrina Jaeger-Honz ◽  
...  

AbstractSpatially resolved transcriptomics is an emerging class of high-throughput technologies that enable biologists to systematically investigate the expression of genes along with spatial information. Upon data acquisition, one major hurdle is the subsequent interpretation and visualization of the datasets acquired. To address this challenge, VR-Cardiomicsis presented, which is a novel data visualization system with interactive functionalities designed to help biologists interpret spatially resolved transcriptomic datasets. By implementing the system in two separate immersive environments, fish tank virtual reality (FTVR) and head-mounted display virtual reality (HMD-VR), biologists can interact with the data in novel ways not previously possible, such as visually exploring the gene expression patterns of an organ, and comparing genes based on their 3D expression profiles. Further, a biologist-driven use-case is presented, in which immersive environments facilitate biologists to explore and compare the heart expression profiles of different genes.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fenghua Tian ◽  
Changtian Li ◽  
Yu Li

Yuanmo [Sarcomyxa edulis (Y.C. Dai, Niemelä & G.F. Qin) T. Saito, Tonouchi & T. Harada] is an important edible and medicinal mushroom endemic to Northeastern China. Here we report the de novo sequencing and assembly of the S. edulis genome using single-molecule real-time sequencing technology. The whole genome was approximately 35.65 Mb, with a G + C content of 48.31%. Genome assembly generated 41 contigs with an N50 length of 1,772,559 bp. The genome comprised 9,364 annotated protein-coding genes, many of which encoded enzymes involved in the modification, biosynthesis, and degradation of glycoconjugates and carbohydrates or enzymes predicted to be involved in the biosynthesis of secondary metabolites such as terpene, type I polyketide, siderophore, and fatty acids, which are responsible for the pharmacodynamic activities of S. edulis. We also identified genes encoding 1,3-β-glucan synthase and endo-1,3(4)-β-glucanase, which are involved in polysaccharide and uridine diphosphate glucose biosynthesis. Phylogenetic and comparative analyses of Basidiomycota fungi based on a single-copy orthologous protein indicated that the Sarcomyxa genus is an independent group that evolved from the Pleurotaceae family. The annotated whole-genome sequence of S. edulis can serve as a reference for investigations of bioactive compounds with medicinal value and the development and commercial production of superior S. edulis varieties.


Author(s):  
Jian-Zhi Huang ◽  
Chih-Peng Lin ◽  
Ting-Chi Cheng ◽  
Ya-Wen Huang ◽  
Yi-Jung Tsai ◽  
...  

Phalaenopsis orchid is an important potted flower with high economic value around the world. We report the 3.1 Gb draft genome assembly of an important winter flowering Phalaenopsis ‘KHM190’ cultivar. We generated 89.5 Gb RNA-seq and 113 million sRNA-seq reads to use these data to identify 41,153 protein-coding genes and 188 miRNA families. We also generated a draft genome for Phalaenopsis pulcherrima ‘B8802’, a summer flowering species, via resequencing. Comparison of genome data between the two Phalaenopsis cultivars allowed the identification of 691,532 single-nucleotide polymorphisms. In this study, we reveal the key role of PhAGL6b in the regulation of flower organ development involves alternative splicing. We also show gibberellin pathways that regulate the expression of genes control flowering time during the stage in reproductive phase change induced by cool temperature. Our work should contribute a valuable resource for the flowering control, flower architecture development, and breeding of the Phalaenopsis orchids.


Background: Craniopharyngioma is a benign tumor of the sellar region that is typically characterized by a maldevelopment tumor with a high recurrence rate, as well as substantial morbidity and mortality in the long term. Signal transducers and transcription activators have been identified as critical components of cytokine signaling pathways that have previously been documented in craniopharyngioma-related literature. Purpose: The primary goal of this investigation is to examine transcription factor expression in craniopharyngiomas. In addition, a clinical-pathological and immunohistochemistry correlation will be sought. The current study enlisted the participation of forty patients. AdaCPs exhibited: β-catenin STAT2, STAT3, STAT6, and HDAC1 expression. While, STAT4, HDAC2, and GATA 3 were all negative. TTF1 was found in proteinaceous substances within the cyst formation (OMF). β-FGR, DPGR, TNFa, and Nrf2 were found to be associated with inflammation, OMF presence, and finger protrusion in brain surrounding tissue or brain invasion. Conclusions: Tumor recurrence was associated with increased expression of STAT3, STAT6, HDAC, β-catenin, and TNFα in WLA when compared to no recurrence. Coexpression of β-catenin, STAT2, STAT3, and STAT6 with TNFα was also shown using double fluorescence merge stains. There was no association between HDAC1 and HDAC2 coexpression and β-catenin, notably in the WLAs. Discussion: Histologically complicated features include cystic and solid components, the latter of which is made up of diverse morphological cell types. HDAC1 and HDAC2 regulate the enhanced expression of inflammatory genes during inflammation and macrophage response.


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