Identifying Diagnostic and Prognostic targets for Papillary Thyroid Carcinoma through mining Gene Expression BIG Datasets using Adaptive Filtering and Advanced Bioinformatics Algorithms

Thyroid Cancer is the most common endocrine malignancy. Although the mortality rate of thyroid cancer is considered to be low, however the reoccurrence and persistence of the disease is still considered high. The most common type of thyroid cancer is papillary thyroid carcinoma consisting of >70% of all types of thyroid cancer. Thyroid cancer is heterogeneous and complex. BIG data in the form of publicly available gene expression (transcriptomics) datasets can provide valuable source to gain deeper understanding of complex diseases such as papillary thyroid carcinoma (PTC). In this study, we used a novel bioinformatics method based on adaptive filtering to reduce the number of genes expressed eliminating genes that are invariant across the various disease stages. In order to shed light on some of the mechanisms involved in PTC, the filtered genes were used in systematic pathway analysis searches across 20,500 annotated cellular pathways using modified Kolmogorov-Smirnov algorithm to identify the relevant differentially activated cellular pathways across the various stages of the disease. Our analysis from 95 PTC patient biopsies consisting of 41 normal, 28 nonaggressive and 26 metastatic papillary thyroid carcinoma revealed 2193 differential activated cellular pathways among non-aggressive samples and 1969 among metastatic samples compared to normal tissue. The key pathways for non-aggressive PTC includes calcium and potassium ion transport, hormone signaling pathways, protein tyrosine phosphatase activity and protein tyrosine kinase activity. The key pathways for metastatic PTC include growth, apoptosis, activation of MAPK activity and regulation of serine threonine kinase activity. The most frequent genes across the enriched pathways were KCNQ1, CACNA1D, KCNN4, BCL2, and PTK2B for non-aggressive PTC, and EGFR, PTK2B, KCNN4 and BCL2 for metastatic PTC. Survival analysis results showed that PTK2B, CACNA1D and BCL2 contributed to poor survival of PTC patients. The study identified insights into mechanisms of PTC

DKK3’s protective role in prostate cancer is partly due to the modulation of immune-related pathways

While it is considered one of the most common cancers and the leading cause of death in men worldwide, prognostic stratification and treatment modalities are still limited for patients with prostate cancer (PCa). Recently, the introduction of genomic profiling and the use of new techniques like next-generation sequencing (NGS) in many cancers provide novel tools for the discovery of new molecular targets that might improve our understanding of the genomic aberrations in PCa and the discovery of novel prognostic and therapeutic targets. In this study, we investigated the possible mechanisms through which Dickkopf-3 (DKK3) produces its possible protective role in PCa using NGS in both the DKK3 overexpression PCa cell line (PC3) model and our patient cohort consisting of nine PCa and five benign prostatic hyperplasia. Interestingly, our results have shown that DKK3 transfection-modulated genes are involved in the regulation of cell motility, senescence-associated secretory phenotype (SASP), and cytokine signaling in the immune system, as well as in the regulation of adaptive immune response. Further analysis of our NGS using our in vitro model revealed the presence of 36 differentially expressed genes (DEGs) between DKK3 transfected cells and PC3 empty vector. In addition, both CP and ACE2 genes were differentially expressed not only between the transfected and empty groups but also between the transfected and Mock cells. The top common DEGs between the DKK3 overexpression cell line and our patient cohort are the following: IL32, IRAK1, RIOK1, HIST1H2BB, SNORA31, AKR1B1, ACE2, and CP. The upregulated genes including IL32, HIST1H2BB, and SNORA31 showed tumor suppressor functions in various cancers including PCa. On the other hand, both IRAK1 and RIOK1 were downregulated and involved in tumor initiation, tumor progression, poor outcome, and radiotherapy resistance. Together, our results highlighted the possible role of the DKK3-related genes in protecting against PCa initiation and progression

Systems Immunology Analysis Reveals the Contribution of Pulmonary and Extrapulmonary Tissues to the Immunopathogenesis of Severe COVID-19 Patients

As one of the current global health conundrums, COVID-19 pandemic caused a dramatic increase of cases exceeding 79 million and 1.7 million deaths worldwide. Severe presentation of COVID-19 is characterized by cytokine storm and chronic inflammation resulting in multi-organ dysfunction. Currently, it is unclear whether extrapulmonary tissues contribute to the cytokine storm mediated-disease exacerbation. In this study, we applied systems immunology analysis to investigate the immunomodulatory effects of SARS-CoV-2 infection in lung, liver, kidney, and heart tissues and the potential contribution of these tissues to cytokines production. Notably, genes associated with neutrophil-mediated immune response (e.g. CXCL1) were particularly upregulated in lung, whereas genes associated with eosinophil-mediated immune response (e.g. CCL11) were particularly upregulated in heart tissue. In contrast, immune responses mediated by monocytes, dendritic cells, T-cells and B-cells were almost similarly dysregulated in all tissue types. Focused analysis of 14 cytokines classically upregulated in COVID-19 patients revealed that only some of these cytokines are dysregulated in lung tissue, whereas the other cytokines are upregulated in extrapulmonary tissues (e.g. IL6 and IL2RA). Investigations of potential mechanisms by which SARS-CoV-2 modulates the immune response and cytokine production revealed a marked dysregulation of NF-κB signaling particularly CBM complex and the NF-κB inhibitor BCL3. Moreover, overexpression of mucin family genes (e.g. MUC3A, MUC4, MUC5B, MUC16, and MUC17) and HSP90AB1 suggest that the exacerbated inflammation activated pulmonary and extrapulmonary tissues remodeling. In addition, we identified multiple sets of immune response associated genes upregulated in a tissue-specific manner (DCLRE1C, CHI3L1, and PARP14 in lung; APOA4, NFASC, WIPF3, and CD34 in liver; LILRA5, ISG20, S100A12, and HLX in kidney; and ASS1 and PTPN1 in heart). Altogether, these findings suggest that the cytokines storm triggered by SARS-CoV-2 infection is potentially the result of dysregulated cytokine production by inflamed pulmonary and extrapulmonary (e.g. liver, kidney, and heart) tissues

KIBRA gene variant is associated with ability in chess and science

The kidney and brain expressed protein (KIBRA) plays an important role in synaptic plasticity. Carriers of the T allele of the KIBRA (WWC1) gene rs17070145 C/T polymorphism have been reported to have enhanced spatial ability and to outperform individuals with the CC genotype in working memory tasks. Since ability in chess and science is directly related to spatial ability and working memory, we hypothesized that the KIBRA T allele would be positively associated with chess player status and PhD status in science. We tested this hypothesis in a study involving 2479 individuals (194 chess players, 119 PhD degree holders in STEM fields, and 2166 controls; 1417 males and 1062 females) from three ethnicities (236 Kazakhs, 1583 Russians, 660 Tatars). We found that frequencies of the T allele were significantly higher in Kazakh (66.9 vs. 55.1%; p = 0.024), Russian (44.8 vs. 32.0%; p = 0.0027), and Tatar (51.5 vs. 41.8%; p = 0.035) chess players compared with ethnically matched controls (meta-analysis for CT/TT vs. CC: OR = 2.05, p = 0.0001). In addition, none of the international chess grandmasters (ranked among the 80 best chess players in the world) were carriers of the CC genotype (0 vs. 46.3%; OR = 16.4, p = 0.005). Furthermore, Russian and Tatar PhD holders had a significantly higher frequency of CT/TT genotypes compared with controls (meta-analysis: OR = 1.71, p = 0.009). Overall, this is the first study to provide comprehensive evidence that the rs17070145 C/T polymorphism of the KIBRA gene may be associated with ability in chess and science, with the T allele exerting a beneficial effect

Bio-composting oil palm waste for improvement of soil fertility

Sources of bio-compost as agro-industrial wastes includes wide range of oil palm wastes viz. waste, biomass, palm kernels, empty fruit bunch, mill effluent, trunk and frond compost. Various composting processes are summarized in brief with distinct reference of oil–palm composting covering aerated static pile, and co-composting with earthworms (vermicomposting). However, in-vessel composting and windrow composting has meritorious advantages in composting. This review article refers to various significant roles played by microorganisms associated. Noteworthy study of bio-compost applications and procedures are correspondingly glosses framework of ecological, economical and agro-ecosystemic benefits