Feedback Trading in Saffron Exchange Traded Funds

Commodity Exchange Traded Funds (ETF) are one type of ETF that underlying assets are agricultural products, energy or metals instead of stocks. These ETFs expose their investors to the market of various commodities in different ways, such as physical commodity, futures of single commodity, futures of baskets commodities, equities with exposures to commodities in various forms. In recent years, this financial instrument has become one of the important investment options among several people by creating many advantages. Despite these developments, scarce evidence exists in the current literature on the feedback trading of ETF investors. The objective of this paper is examination of feedback trading in behavior investors of Saffron ETF in Iran. For this purpose, daily data of two Saffron ETF for January 3, 2021 - Novenber 11, 2022 and Sentana and Wadhwani (1992) model was used. Empirical analysis suggests that volatility of fund return is symmetrical against the news. Despite a formal market with full overlapping for the underlying assets, Saffron ETFs investors do not notice about the difference between ETFs' market prices and their Net Asset Value (NAV). The results of the feedback trading model show that there is no evidence of feedback trading in Saffron ETF. It seems that the market of Saffron ETF is efficient, which can be related to the specificity of the underlying assets and the investors of these ETFs

Expanded Somatic Mutation Spectrum of MED12 Gene in Uterine Leiomyomas of Saudi Arabian Women

MED12, a subunit of mediator complex genes is known to harbor genetic mutations, (mostly in exon 2), causal to the genesis of uterine leiomyomas among Caucasian, African American, and Asian women. However, the precise relationship between genetic mutations vs. protein or disease phenotype is not well-explained. Therefore, we sought to replicate the MED12 mutation frequency in leiomyomas of Saudi Arabian women, who represents ethnically and culturally distinct population. We performed molecular screening of MED12 gene (in 308 chromosomes belonging to 154 uterine biopsies), analyzed the genotype-disease phenotype correlations and determined the biophysical characteristics of mutated protein through diverse computational approaches. We discovered that >44% (34/77) leiomyomas of Arab women carry a spectrum of MED12 mutations (30 missense, 1 splice site, and 3 indels). In addition to known codon 44, we observed novel somatic mutations in codons 36, 38, and 55. Most genetically mutated tumors (27/30; 90%) demonstrated only one type of genetic change, highlighting that even single allele change in MED12 can have profound impact in transforming the normal uterine myometrium to leiomyomas. An interesting inverse correlation between tumor size and LH is observed when tumor is positive to MED12 mutation (p < 0.05). Our computational investigations suggest that amino acid substitution mutations in exon-2 region of MED12 might contribute to potential alterations in phenotype as well as the stability of MED12 protein. Our study, being the first one from Arab world, confirms the previous findings that somatic MED12 mutations are critical to development and progression of uterine leiomyomas irrespective of the ethnic background. We recommend that mutation screening, particularly codon 44 of MED12 can assist in molecular diagnostics of uterine leiomyomas in majority of the patients

Computational Protein Phenotype Characterization of IL10RA Mutations Causative to Early Onset Inflammatory Bowel Disease (IBD)

The deleterious amino acid substitution mutations in IL-10 receptor alpha gene are most frequently reported in several autoimmune diseases including early onset-inflammatory bowel disease (IBD). Despite the important role of IL-10 RA in maintaining immune homeostasis, the specific structural and functional implications of these mutations on protein phenotype, stability, ligand binding and post translational characteristics is not well explored. Therefore, this study performed the multidimensional computational analysis of IL10RA missense variations causative to pediatric or early onset inflammatory bowel disease (<5 years of age). Our computational algorithmic screening identified the deleterious nature of p. W45G, p. Y57C, p. W69G, p.T84I, p.Y91C, p.R101W, p.R117C, and p.R117H, IBD causative IL10-RA mutations. The sensitivity and specificity analysis of different computational methods showed that CADD outperform SIFT, PolyPhen 2.0, FATHMM, LRT, MetaLR, MetaSVM, PROVEAN and Condel in predicting the pathogenicity of IL10RA mutations. Our three-dimensional protein modeling assays showed that the point mutations cause major drifts in the structural plasticity of IL10 RA molecule and negatively influence its stability. Findings from molecular docking analysis have shown that these point mutations decrease the binding affinity of IL10RA toward IL10 and may likely to disturb the IL10 signaling pathway. This study provides an easy frame work for phenotypic characterization of mutant IL10RA molecule in terms of structure, flexibility and stability aspects. Our approach may also add a new dimension to conventional functional biology assays in quickly studying IL10 RA mutations and also for designing and developing inhibitors for mutant IL10RA molecule

Trabecular Bone Score and Bone Mineral Density in Postmenopausal Women with Morbid Obesity—A Clinical Paradox

Obesity has long been considered to have a protective effect on bone, but specific complications in those with morbid obesity are known to have a detrimental impact on bone architecture. We aimed to study the bone microarchitecture (TBS—trabecular bone score) and bone mineral density (BMD) in postmenopausal women with morbid obesity compared to obese and non-obese age-matched women. Eighty-five consecutive postmenopausal women with morbid obesity (body mass index (BMI) ≥ 35 kg/m2) were enrolled and compared to age-matched obese (n = 80) and non-obese postmenopausal controls (n = 85). The BMD and TBS were assessed in all subjects using a Hologic-QDR 4500-W Discovery-A DXA scanner. The mean BMD (gm/cm2) at the femoral neck in women with morbid obesity was found to be significantly lower as compared to the age-matched postmenopausal obese controls (0.723 versus 0.762, p-value = 0.002). The BMD at the lumbar spine and hip showed similar trends but were not statistically significant. The bone microarchitecture was found to be significantly lower in those with morbid obesity (1.205) as compared to the other two groups (obesity 1.244; non-obese 1.228) (p < 0.013). Though obesity was associated with a better bone density and bone microarchitecture in postmenopausal women, a paradoxical lower value was seen in those with morbid obesity

<i>In-Silico</i> Analysis of Inflammatory Bowel Disease (IBD) GWAS Loci to Novel Connections

<div><p>Genome-wide association studies (GWASs) for many complex diseases, including inflammatory bowel disease (IBD), produced hundreds of disease-associated loci—the majority of which are noncoding. The number of GWAS loci is increasing very rapidly, but the process of translating single nucleotide polymorphisms (SNPs) from these loci to genomic medicine is lagging. In this study, we investigated 4,734 variants from 152 IBD associated GWAS loci (IBD associated 152 lead noncoding SNPs identified from pooled GWAS results + 4,582 variants in strong linkage-disequilibrium (LD) (<i>r²</i> ≥0.8) for EUR population of 1K Genomes Project) using four publicly available bioinformatics tools, e.g. dbPSHP, CADD, GWAVA, and RegulomeDB, to annotate and prioritize putative regulatory variants. Of the 152 lead noncoding SNPs, around 11% are under strong negative selection (GERP++ RS ≥2); and ~30% are under balancing selection (Tajima’s D score >2) in CEU population (1K Genomes Project)—though these regions are positively selected (GERP++ RS <0) in mammalian evolution. The analysis of 4,734 variants using three integrative annotation tools produced 929 putative functional SNPs, of which 18 SNPs (from 15 GWAS loci) are in concordance with all three classifiers. These prioritized noncoding SNPs may contribute to IBD pathogenesis by dysregulating the expression of nearby genes. This study showed the usefulness of integrative annotation for prioritizing fewer functional variants from a large number of GWAS markers.</p></div

Identification of key regulatory genes connected to NF-κB family of proteins in visceral adipose tissues using gene expression and weighted protein interaction network.

Obesity is connected to the activation of chronic inflammatory pathways in both adipocytes and macrophages located in adipose tissues. The nuclear factor (NF)-κB is a central molecule involved in inflammatory pathways linked to the pathology of different complex metabolic disorders. Investigating the gene expression data in the adipose tissue would potentially unravel disease relevant gene interactions. The present study is aimed at creating a signature molecular network and at prioritizing the potential biomarkers interacting with NF-κB family of proteins in obesity using system biology approaches. The dataset GSE88837 associated with obesity was downloaded from Gene Expression Omnibus (GEO) database. Statistical analysis represented the differential expression of a total of 2650 genes in adipose tissues (p = <0.05). Using concepts like correlation, semantic similarity, and theoretical graph parameters we narrowed down genes to a network of 23 genes strongly connected with NF-κB family with higher significance. Functional enrichment analysis revealed 21 of 23 target genes of NF-κB were found to have a critical role in the pathophysiology of obesity. Interestingly, GEM and PPP1R13L were predicted as novel genes which may act as potential target or biomarkers of obesity as they occur with other 21 target genes with known obesity relationship. Our study concludes that NF-κB and prioritized target genes regulate the inflammation in adipose tissues through several molecular signaling pathways like NF-κB, PI3K-Akt, glucocorticoid receptor regulatory network, angiogenesis and cytokine pathways. This integrated system biology approaches can be applied for elucidating functional protein interaction networks of NF-κB protein family in different complex diseases. Our integrative and network-based approach for finding therapeutic targets in genomic data could accelerate the identification of novel drug targets for obesity

Top MCODE clusters from the gene interaction network.

<p>Highly connected gene clusters were identified from the network using MCODE v1.32 (a Cytoscape 2.8.2 plugin) and the top 11 clusters are presented (cutoff score ≥1).</p

Gene interaction network using GeneMANIA webserver.

<p>Here genes are represented as nodes and edges indicate different types of interaction between genes. Black circles are the query genes and the color coding on edges indicate different types of interaction—which is defined in the network legend.</p

Distribution of (a) CADD and (b) GWAVA scores.

<p>Histograms are drawn taking CADD and GWAVA scores of all the variants (lead GWAS SNPs and LD variants) after removing the missing values. Here n = 4781 for CADD and n = 4460 variants for GWAVA.</p