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The estrogen receptor 1 gene (ESR1) plays a crucial role in breast and mammary development in humans. Alterations such as gene amplification, genomic rearrangements, and missense mutations in the ESR1 gene are reported to increase the risk of breast cancer in humans. The purpose of this study is to analyze the missense mutations and molecular modeling of ESR1, focusing on the pathogenic SNP H516N, for a better understanding of disease risk and future benefits for therapeutic benefits. This SNP was selected based on its location in the binding pocket of ESR1 and its predicted impact on drug binding. The in silico analysis was performed by applying various computational approaches to identify highly pathogenic SNPs in the binding pocket of ESR1. The effect of the SNP was explored through docking and intra-molecular interaction studies. All SNPs in ESR1 were identified followed by the identification of the highly pathogenic variant located in the binding pocket of ESR1. The mutant model of the pathogenic SNP H516N was generated, and hydroxytamoxifen was docked with the wild-type and the mutant model. The mutant model lost the formation of stable hydrogen bonds with the active site residues and hydroxytamoxifen, which may result in reduced binding affinity and therefore, will predict the patient's response to estrogenic inhibitors.

Background/Aims: The main focus of this investigation is to identify deleterious single nucleotide polymorphisms (SNPs) located in the BRCA2 gene through in silico approach, thereby, providing an understanding of potential consequences regarding the susceptibility to breast cancer. Methods: The GenomAD database was used to identify SNPs. To determine the potential adverse consequences, our study employed various prediction tools, including SIFT, PolyPhen, PredictSNP, SNAP2, PhD-SNP, and ClinVar. The pathogenicity associated with the deleterious snSNPs was evaluated bu MutPred and Fathmm. Additionally, I-Mutant and MuPro were used to assess the stability, followed by conservation and protein-protein interaction analysis using robust computational tools. The 3D structure of BRCA2 protein was generated by SwissModel, followed by validation using PROCHECK and Errat. Results: The GenomAD database was used to identify a total of 7, 921 SNPs, including 1940 missense SNPs. A set of 69 SNPs predicted by consensus to be damaging across all platforms was identified. Mutpred and Fathmm identified 48 and 38 SNPs, respectively to be associated with cancer. While I- Mutant and MuPro assays suggested 22 SNPs to decrease protein stability. Additionally, these 22 SNPs reside within highly conserved regions of the BRCA2 protein. Domain analysis, utilizing InterPro, pinpointed 18 deleterious mutations within crucial DNA binding domains and one in the BRC repeat region. Conclusion: This study establishes a foundation for future experimental validations and the creation of breast cancer-targeted treatment approaches.

Abstract Background and Aims Breast cancer is the most common type of cancer in women. The genetic polymorphism in HER (HER1–rs11543848 and HER2–rs1136201) were found to be associated with breast cancer risk in different ethnicities worldwide with inconsistent results. The aim of this research study was to evaluate the association of HER1–rs11543848 and HER2–rs1136201 polymorphisms as a risk of breast cancer in Pashtun population of Khyber Pakhtunkhwa, Pakistan. Methods A total of 314 women including 164 breast cancer patients and 150 age and gender‐matched healthy controls were enrolled from June 2021 to May 2022. All the samples were subjected to DNA extraction followed by Tetra‐ARMS‐PCR for genotyping and gel electrophoresis. Results Our results indicated that HER1–rs11543848 risk allele A (p = 0.0001) and heterozygous genotype GA (p = 0.0001) displayed highly significant association with breast cancer, while the homozygous mutant genotype AA indicated association but nonsignificant results (odds ratio [OR] = 2.637, 95% confidence interval [CI] = 1.2258–5.6756, p = 0.0833). Similarly, the HER2–rs1136201 risk allele G (p = 0.0023), the heterozygous genotype AG (p = 0.0530) and homozygous mutant genotype GG showed significant association (OR = 2.5946, 95% CI = 0.9876–6.8165, p = 0.0530) with breast cancer risk. Both the SNPs presented a higher but nonsignificant risk of breast cancer in postmenopausal women (OR = 2.242, p = 0.08 and OR = 2.009, p = 0.06). However, both the SNPs showed significant association (p

Despite the growth of molecular diagnosis from the era of Hippocrates, the emergence of COVID-19 is still remarkable. The previously used molecular techniques were not rapid enough to screen a vast population at home, in offices, and in hospitals. Additionally, these techniques were only available in advanced clinical laboratories.The pandemic outbreak enhanced the urgency of researchers and research and development companies to invent more rapid, robust, and portable devices and instruments to screen a vast community in a cost-effective and short time. There has been noteworthy progress in molecular diagnosing tools before and after the pandemic. This review focuses on the advancements in molecular diagnostic techniques before and after the emergence of COVID-19 and how the pandemic accelerated the implantation of molecular diagnostic techniques in most clinical laboratories towardbecoming routine tests.

Superior mesenteric artery (SMA) syndrome is a rare cause of duodenal obstruction that can go undiagnosed, exacerbating weight loss in an already significantly malnourished patient. Diagnosis is often challenging, however, can be made by keeping a high index of suspicion based on the clinical presentation. The pathology involves a reduction in the amount of fat pad between the abdominal aorta and superior mesenteric artery (SMA) leading to a reduction of aorto-mesenteric angle and consequent compression of mostly third part of the duodenum. Management is usually conservative, however, if conservative treatment fails, surgical intervention is warranted.Our patient was a 20-year-old female who presented to us with nausea, vomiting, weight loss, and abdominal pain. The presence of obstructive symptoms along with imaging (CT scan) lead to the diagnosis of SMA syndrome and she improved with conservative management. Informed consent was obtained for this study.

The grain number per panicle (GNP) is an important yield component. Identifying naturally favorable variations in GNP will benefit high-yield rice breeding. Here, we performed a genome-wide association study using a mini-core collection of 266 cultivated rice accessions with deep sequencing data and investigated the phenotype for three years. Three genes, i.e., TOTOU1 (TUT1), Grain height date 7 (Ghd7), and Days to heading 7/Grain height date 7.1/Pseudo-Response Regulator37 (DTH7/Ghd7.1/OsPRR37), which regulate GNP, were found in the quantitative trait loci (QTL) identified in this study. A stable QTL, qGNP1.3, which showed a strong correlation with variations in GNP, was repeatedly detected. After functional and transgenic phenotype analysis, we identified a novel gene, regulator of grain number 1a (RGN1a), which codes for protein kinase, controlling GNP in rice. The RGN1a mutation caused 37.2%, 27.8%, 51.2%, and 25.5% decreases in grain number, primary branch number per panicle, secondary branch number per panicle, and panicle length, respectively. Furthermore, breeding utilization analysis revealed that the additive effects of the dominant allelic variants of RGN1a and DTH7 played a significant role in increasing the grain number per panicle in japonica rice. Our findings enrich the gene pool and provide an effective strategy for the genetic improvement of grain numbers.

The genome contributes to the uniqueness of an individual breed, and enables distinctive characteristics to be passed from one generation to the next. The allelic heterogeneity of a certain breed results in a different response to a pathogen with different genomic expression. Disease resistance in chicken is a polygenic trait that involves different genes that confer resistance against pathogens. Such resistance also involves major histocompatibility (MHC) molecules, immunoglobulins, cytokines, interleukins, T and B cells, and CD4+ and CD8+ T lymphocytes, which are involved in host protection. The MHC is associated with antigen presentation, antibody production, and cytokine stimulation, which highlight its role in disease resistance. The natural resistance-associated macrophage protein 1 (Nramp-1), interferon (IFN), myxovirus-resistance gene, myeloid differentiation primary response 88 (MyD88), receptor-interacting serine/threonine kinase 2 (RIP2), and heterophile cells are involved in disease resistance and susceptibility of chicken. Studies related to disease resistance genetics, epigenetics, and quantitative trait loci would enable the identification of resistance markers and the development of disease resistance breeds. Microbial infections are responsible for significant outbreaks and have blighted the poultry industry. Breeding disease-resistant chicken strains may be helpful in tackling pathogens and increasing the current understanding on host genetics in the fight against communicable diseases. Advanced technologies, such as the CRISPR/Cas9 system, whole genome sequencing, RNA sequencing, and high-density single nucleotide polymorphism (SNP) genotyping, aid the development of resistant breeds, which would significantly decrease the use of antibiotics and vaccination in poultry. In this review, we aimed to reveal the recent genetic basis of infection and genomic modification that increase resistance against different pathogens in chickens.

The yield of rice is mostly affected by three factors, namely, panicle number, grain number and grain weight. Variation in panicle and grain numbers is mainly caused by tiller and panicle branches generated from axillary meristems (AMs). MOC1 encodes a putative GRAS family nuclear protein that regulates AM formation. Although several alleles of MOC1 have been identified, its variation in germplasm resources remains unclear. In the present study we characterized a novel moc1 allele named gnp6 which has a thymine insertion in the coding sequence of the SAW motif in the GRAS domain. This mutation causes arrested branch formation. The SAW motif is necessary for nuclear localization of GNP6/MOC1 where it functions as a transcription factor or co-regulator. Haplotype analysis showed that the coding region of GNP6/MOC1 was conserved without any non-synonymous mutations in 240 rice accessions. However, variation in the promoter region might affect the expression of it and its downstream genes. Joint haplotype analysis of GNP6/MOC1 and MOC3 showed that haplotype combinations H9, H10 and H11, namely MOC1-Hap1 in combination with MOC3-Hap3, MOC3-Hap4 or MOC3-Hap5 could be bred to promote branch formation. These findings will enrich the genetic resources available for rice breeders.

The aim of the present study was to find the effect of crushed wild Cumin (Bonium persicum) seeds as a feed additive in broiler diet during the starter phase on growth performance, nutrient digestibility and blood metabolites in broilers. For this purpose, 360 day old chicks were randomly divided into four groups. One group was the control while other experimental groups were supplemented with crushed wild Cumin (WC) seeds in the feed at the rate of 0.5 (WC1), 1 (WC2) and 1.5 g/kg (WC3). Results indicated that feed intake was significantly lower (p

Heading date is a crucial agronomic trait. However, rice usually delays heading due to the photoperiod, temperature, hormones or age. The present research was conducted to analyze the mechanism controlling heading date in F1 hybrid rice. We constructed two test-crossing populations using two introgression lines (ILs), P20 and P21 coming from SH527/FH838 as the male parent, respectively, and male sterile line Jin23A as the female parent. Meanwhile, the F1 hybrids of H20, obtained by mating P20 with Jin23A and having no heading, and H21, from the crossing between P21 and Jin23A having normal heading, were both observed under long days. Here, we analyzed the photoperiodic response of F1 hybrids by transcriptome and metabolome profiling. The greater differences displayed in the transcriptome and the metabolome were caused by photoperiod (exogenous) instead of genes (endogenous). The coping mechanism resulted from long days (LD) in H20, leading to differences in the circadian rhythm and glutathione metabolism relative to other samples. The circadian oscillator and GSH/GSSG cycle typically regulate ROS homeostasis, and both of them are responsible for modulating ROS in H20 under LD condition. Both circadian rhythm genes and the reported genes related to heading date function via the DHD1/OsMFT1-Ehd1-RFT1-OsMADS14/OsMADS18 pathway and the glutathione metabolism pathway by regulating oxidative reduction processes. Both pathways are involved in the heading process and they interacted through the oxidative reduction process which was induced by photoperiod regulation, and all of them collectively modulated the heading process. The results of this study will be helpful for unraveling the mechanism of F1 hybrid responses to unheading under LD condition.

Abstract Hepatocellular carcinoma is a primary liver malignancy in which the risk of development is always multifunctional. Interleukin-6 is a proinflammatory and multifunctional cytokine, which plays an important role in the immune response, haematopoiesis and defence against viral infection. We aimed to evaluate the frequency of Interleukin-6 mutations (rs2069837 and rs17147230) associated with genetic risk of hepatocellular carcinoma in Khyber Pakthunkhwa population. A total of 72 hepatocellular carcinoma cases and 38 controls were included in this study. The genomic DNA was extracted from the peripheral blood cells and Interleukin-6 genotyping was performed using T-ARMS-PCR technique. Our results show a significant increase risk of developing hepatocellular carcinoma with the mutation within Interleukin-6 gene with heterozygous G allele (rs2069837) (OR = 10.667, 95%CI = 3.923–29.001, p =

MoHrip2 Magnaporthe oryzae hypersensitive protein 2 is an elicitor protein of rice blast fungus M. oryzae. Rice seedlings treated with MoHrip2 have shown an induced resistance to rice blast. To elucidate the mechanism underlying this MoHrip2 elicitation in rice, we used differential-display 2-D gel electrophoresis and qRT-PCR to assess the differential expression among the total proteins extracted from rice leaves at 24 h after treatment with MoHrip2 and buffer as a control. Among ~1000 protein spots detected on each gel, 10 proteins were newly induced, 4 were up-regulated, and 3 were down-regulated in MoHrip2-treated samples compared with the buffer control. Seventeen differentially expressed proteins were detected using MS/MS analysis and categorized into six groups according to their putative function: defense-related transcriptional factors, signal transduction-related proteins, reactive oxygen species (ROS) production, programmed cell death (PCD), defense-related proteins, and photosynthesis and energy-related proteins. The qPCR results (relative expression level of genes) further supported the differential expression of proteins in MoHrip2-treated rice leaves identified with 2D-gel, suggesting that MoHrip2 triggers an early defense response in rice leaves via stress-related pathways, and the results provide evidence for elicitor-induced resistance at the protein level.