Integrated gene expression profiling and functional enrichment analyses to discover biomarkers and pathways associated with Guillain-Barré syndrome and autism spectrum disorder to identify new therapeutic targets.

Guillain-Barré syndrome (GBS) is one of the most prominent and acute immune-mediated peripheral neuropathy, while autism spectrum disorders (ASD) are a group of heterogeneous neurodevelopmental disorders. The complete mechanism regarding the neuropathophysiology of these disorders is still ambiguous. Even after recent breakthroughs in molecular biology, the link between GBS and ASD remains a mystery. Therefore, we have implemented well-established bioinformatic techniques to identify potential biomarkers and drug candidates for GBS and ASD. 17 common differentially expressed genes (DEGs) were identified for these two disorders, which later guided the rest of the research. Common genes identified the protein-protein interaction (PPI) network and pathways associated with both disorders. Based on the PPI network, the constructed hub gene and module analysis network determined two common DEGs, namely CXCL9 and CXCL10, which are vital in predicting the top drug candidates. Furthermore, coregulatory networks of TF-gene and TF-miRNA were built to detect the regulatory biomolecules. Among drug candidates, imatinib had the highest docking and MM-GBSA score with the well-known chemokine receptor CXCR3 and remained stable during the 100 ns molecular dynamics simulation validated by the principal component analysis and the dynamic cross-correlation map. This study predicted the gene-based disease network for GBS and ASD and suggested prospective drug candidates. However, more in-depth research is required for clinical validation.Communicated by Ramaswamy H. Sarma.

17 common differentially expressed genes (DEGs) were identified from 693 DEGs of the GBS dataset (GSE72748) and 365 DEGs of the ASD dataset (GSE113834), which is the preliminary part of this investigation.From the PPI network analysis, a total of 10 hub genes were identified and two common DEGs named CXCL9 and CXCL10 were found in both the hub gene and essential module analysis.The identified leading pathways and GO pathways, TF-gene interaction, and TF-miRNAs network has made the process more relevant and appropriate for suggesting probable drug candidates.Among the drug candidates, imatinib was suggested as the main drug candidate due to its interaction with the hub gene CXCL9 and CXCL10 and lower p value than the other candidates. It showed the highest binding affinity score and remained stable with the CXCR3 chemokine receptor.

The function of bacterial HtrA is evolutionally conserved in mammalian HtrA2/Omi.

Although the malfunction of HtrA2/Omi leads to Parkinson's disease (PD), the underlying mechanism has remained unknown. Here, we showed that HtrA2/Omi specifically removed oligomeric α-Syn but not monomeric α-Syn to protect oligomeric α-Syn-induced neurodegeneration. Experiments using mnd2 mice indicated that HtrA2/Omi degraded oligomeric α-Syn specifically without affecting monomers. Transgenic Drosophila melanogaster experiments of the co-expression α-Syn and HtrA2/Omi and expression of genes individually also confirmed that pan-neuronal expression of HtrA2/Omi completely rescued Parkinsonism in the α-Syn-induced PD Drosophila model by specifically removing oligomeric α-Syn. HtrA2/Omi maintained the health and integrity of the brain and extended the life span of transgenic flies. Because HtrA2/Omi specifically degraded oligomeric α-Syn, co-expression of HtrA2/Omi and α-Syn in Drosophila eye maintained a healthy retina, while the expression of α-Syn induced retinal degeneration. This work showed that the bacterial function of HtrA to degrade toxic misfolded proteins is evolutionarily conserved in mammalian brains as HtrA2/Omi.

Combined effect of salt stress and Xanthomonas axonopodis pv citri on citrus (Citrus aurantifolia).

Xanthomonas axonopodis pv citri (Xac) and salt stress are two crucial hindrances to citrus production. The effect of continuous salt application and Xac infection in citrus has been investigated. Citrus plants were exposed to salt stress by irrigating with 50 mM, 100 mM, 150 mM, and 200 mM NaCl solution on weekly basis and challenged by Xac. Salt stress affected the defense response of Citrus plants to Xac and therefore lesion diameter and disease severity were gradually increased at higher salt concentration. Meanwhile, accumulation of Na+ and Cl- in the leaves were also increased with the increase of salt concentration. Besides, physiological performance (PP) of plants was estimated based on the parameters such as net assimilation rate, chlorophyll content, stomatal conductance, transpiration rate and intercellular CO2 concentration. The PP of sole Xac treated plants was gradually increased and maintained up to end of the experiment, whereas plants treated with Xac+50 mM and Xac+100 mM NaCl showed the highest PP up to 30 days after inoculation and then decreased. However, the PP of Xac+150 mM and Xac+200 mM NaCl treated plants gradually decreased till the end of experiment. Similarly, the PP of 200 mM NaCl treated plants declined continuously. Interestingly, the PP in 50 mM and 100 mM NaCl treated plants was higher initially and then decreased at 30 DAI to 40 DAI. This study revealed that citrus canker disease development was enhanced by salt stress. In addition, the physiological performance of the plants was enhanced by Xac and Xac + moderate salt stress but then demolished under severe salt stress.

Discovering Biomarkers and Pathways Shared by Alzheimer's Disease and Ischemic Stroke to Identify Novel Therapeutic Targets.

Background and objectives: Alzheimer's disease (AD) is a progressive neurodegenerative disease that results in severe dementia. Having ischemic strokes (IS) is one of the risk factors of the AD, but the molecular mechanisms that underlie IS and AD are not well understood. We thus aimed to identify common molecular biomarkers and pathways in IS and AD that can help predict the progression of these diseases and provide clues to important pathological mechanisms. Materials and Methods: We have analyzed the microarray gene expression datasets of IS and AD. To obtain robust results, combinatorial statistical methods were used to analyze the datasets and 26 transcripts (22 unique genes) were identified that were abnormally expressed in both IS and AD. Results: Gene Ontology (GO) and KEGG pathway analyses indicated that these 26 common dysregulated genes identified several altered molecular pathways: Alcoholism, MAPK signaling, glycine metabolism, serine metabolism, and threonine metabolism. Further protein-protein interactions (PPI) analysis revealed pathway hub proteins PDE9A, GNAO1, DUSP16, NTRK2, PGAM2, MAG, and TXLNA. Transcriptional and post-transcriptional components were then identified, and significant transcription factors (SPIB, SMAD3, and SOX2) found. Conclusions: Protein-drug interaction analysis revealed PDE9A has interaction with drugs caffeine, γ-glutamyl glycine, and 3-isobutyl-1-methyl-7H-xanthine. Thus, we identified novel putative links between pathological processes in IS and AD at transcripts levels, and identified possible mechanistic and gene expression links between IS and AD.

Programmable Molecular Scissors: Applications of a New Tool for Genome Editing in Biotech.

Targeted genome editing is an advanced technique that enables precise modification of the nucleic acid sequences in a genome. Genome editing is typically performed using tools, such as molecular scissors, to cut a defined location in a specific gene. Genome editing has impacted various fields of biotechnology, such as agriculture; biopharmaceutical production; studies on the structure, regulation, and function of the genome; and the creation of transgenic organisms and cell lines. Although genome editing is used frequently, it has several limitations. Here, we provide an overview of well-studied genome-editing nucleases, including single-stranded oligodeoxynucleotides (ssODNs), transcription activator-like effector nucleases (TALENs), zinc-finger nucleases (ZFNs), and CRISPR-Cas9 RNA-guided nucleases (CRISPR-Cas9). To this end, we describe the progress toward editable nuclease-based therapies and discuss the minimization of off-target mutagenesis. Future prospects of this challenging scientific field are also discussed.

Ultra-High Efficient Colony PCR for High Throughput Screening of Bacterial Genes.

Current colony PCR methods are not suitable for screening genes encoded in genomic DNA and are limited to E. coli host strains. Here, we describe an ultra-high efficient colony PCR method for high throughput screening of bacterial genes embedded in the genomic DNA of any bacterial species. This new technique expands colony PCR method to several hosts as well as offers a rapid, less expensive and reliable bacterial genomic DNA extraction.