scholarly journals Comprehensive Analysis of the Immune Infiltrates and Aberrant Pathways Activation in Atherosclerotic Plaque

2021 ◽  
Vol 7 ◽  
Author(s):  
Hukui Han ◽  
Rongsheng Du ◽  
Panke Cheng ◽  
Jiancheng Zhang ◽  
Yang Chen ◽  
...  

Atherosclerosis is the pathological basis of many cardiovascular and cerebrovascular diseases. The development of gene chip and high-throughput sequencing technologies revealed that the immune microenvironment of coronary artery disease (CAD) in high-risk populations played an important role in the formation and development of atherosclerotic plaques. Three gene expression datasets related to CAD were assessed using high-throughput profiling. CIBERSORT analysis revealed significant differences in five types of immune cells: activated dendritic cells (DCs), T follicular helper cells (Tfhs), resting CD4+ T cells, regulatory T cells (Tregs), and γδ T cells. Immune transcriptome analysis indicated higher levels of inflammatory markers (cytolytic activity, antigen presentation, chemokines, and cytokines) in the cases than in the controls. The level of activated DCs and the lipid clearance signaling score were negatively correlated. We observed a positive correlation between the fraction of Tfhs and lipid biosynthesis. Resting CD4+ T cells and the activity of pathways related to ossification in bone remodeling and glutathione synthesis showed a negative correlation. Gamma delta T cells negatively correlated with IL-23 signaling activity. GSEA revealed a close association with the inflammatory immune microenvironment. The present study revealed that CAD patients may have an inflammatory immune microenvironment and provides a timely update on anti-inflammatory therapies under current investigation.

Author(s):  
Stella C. Yuan ◽  
Eric Malekos ◽  
Melissa T. R. Hawkins

AbstractThe use of museum specimens held in natural history repositories for population and conservation genetic research is increasing in tandem with the use of massively parallel sequencing technologies. Short Tandem Repeats (STRs), or microsatellite loci, are commonly used genetic markers in wildlife and population genetic studies. However, they traditionally suffered from a host of issues including length homoplasy, high costs, low throughput, and difficulties in reproducibility across laboratories. Massively parallel sequencing technologies can address these problems, but the incorporation of museum specimen derived DNA suffers from significant fragmentation and exogenous DNA contamination. Combatting these issues requires extra measures of stringency in the lab and during data analysis, yet there have not been any high-throughput sequencing studies evaluating microsatellite allelic dropout from museum specimen extracted DNA. In this study, we evaluate genotyping errors derived from mammalian museum skin DNA extracts for previously characterized microsatellites across PCR replicates utilizing high-throughput sequencing. We found it useful to classify samples based on DNA concentration, which determined the rate by which genotypes were accurately recovered. Longer microsatellites performed worse in all museum specimens. Allelic dropout rates across loci were dependent on sample quantity, with high concentration museum specimens performing as well and recovering quality metrics nearly as high as the frozen tissue sample. Based on our results, we provide a set of best practices for quality assurance and incorporation of reliable genotypes from museum specimens.


2009 ◽  
Vol 257 (1-2) ◽  
pp. 69-79 ◽  
Author(s):  
Deborah M. Brown ◽  
Cris Kamperschroer ◽  
Allison M. Dilzer ◽  
Deborah M. Roberts ◽  
Susan L. Swain

2016 ◽  
Vol 22 (10) ◽  
pp. 1192-1192 ◽  
Author(s):  
Carsten Linnemann ◽  
Marit M van Buuren ◽  
Laura Bies ◽  
Els M E Verdegaal ◽  
Remko Schotte ◽  
...  

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0163288 ◽  
Author(s):  
Christine L. Vigeland ◽  
Samuel L. Collins ◽  
Yee Chan-Li ◽  
Andrew H. Hughes ◽  
Min-Hee Oh ◽  
...  

2019 ◽  
Author(s):  
Reneth Millas ◽  
Mary Espina ◽  
CM Sabbir Ahmed ◽  
Angelina Bernardini ◽  
Ekundayo Adeleke ◽  
...  

ABSTRACTOne of the most important tools in genetic improvement is mutagenesis, which is a useful tool to induce genetic and phenotypic variation for trait improvement and discovery of novel genes. JTN-5203 (MG V) mutant population was generated using an induced ethyl methane sulfonate (EMS) mutagenesis and was used for detection of induced mutations in FAD2-1A and FAD2-1B genes using reverse genetics approach. Optimum concentration of EMS was used to treat 15,000 bulk JTN-5203 seeds producing 1,820 M2 population. DNA was extracted, normalized, and pooled from these individuals. Specific primers were designed from FAD2-1A and FAD2-1B genes that are involved in the fatty acid biosynthesis pathway for further analysis using next-generation sequencing. High throughput mutation discovery through TILLING-by-Sequencing approach was used to detect novel allelic variations in this population. Several mutations and allelic variations with high impacts were detected for FAD2-1A and FAD2-1B. This includes GC to AT transition mutations in FAD2-1A (20%) and FAD2-1B (69%). Mutation density for this population is estimated to be about 1/136kb. Through mutagenesis and high-throughput sequencing technologies, novel alleles underlying the mutations observed in mutants with reduced polyunsaturated fatty acids will be identified, and these mutants can be further used in breeding soybean lines with improved fatty acid profile, thereby developing heart-healthy-soybeans.


Author(s):  
AA Kliuchnikova ◽  
SA Moshkovskii

Adenosine-to-inosine (A-to-I) RNA editing is a common mechanism of post-transcriptional modification in many metazoans including vertebrates; the process is catalyzed by adenosine deaminases acting on RNA (ADARs). Using high-throughput sequencing technologies resulted in finding thousands of RNA editing sites throughout the human transcriptome however, their functions are still poorly understood. The aim of this brief review is to draw attention of clinicians and biomedical researchers to ADAR-mediated RNA editing phenomenon and its possible implication in development of neuropathologies, antiviral immune responses and cancer.


2011 ◽  
Vol 4 (4) ◽  
pp. 211
Author(s):  
Serena Meraviglia ◽  
Carmela La Mendola ◽  
Valentina Orlando ◽  
Francesco Scarpa ◽  
Giuseppe Cicero ◽  
...  

The potent anti-tumor activities of γδ T cells, their ability to produce pro-inflammatory cytokines, and their strong cytolytic activity have prompted the development of protocols in which γδ agonists or ex vivo-expanded γδ cells are administered to tumor patients. γδ T cells can be selectively activated by either synthetic phosphoantigens or by drugs that enhance their accumulation into stressed cells as aminobisphosphonates, thus offering new avenues for the development of γδ T cell-based immunotherapies. The recent development of small drugs selectively activating Vγ9Vδ2 T lymphocytes, which upregulate the endogenous phosphoantigens, has enabled the investigators to design the experimental approaches of cancer immunotherapies; several ongoing phase I and II clinical trials are focused on the role of the direct bioactivity of drugs and of adoptive cell therapies involving phosphoantigen- or aminobisphosphonate-activated Vγ9Vδ2 T lymphocytes in humans. In this review, we focus on the recent advances in the activation/expansion of γδ T cells in vitro and in vivo that may represent a promising target for the design of novel and highly innovative immunotherapy in patients with hematologic malignancies.<br />


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