Smyd3-mediated immuno-modulation in HPV-negative head and neck squamous cell carcinoma mouse models.

SET and MYND-domain containing protein 3 (SMYD3) mediates epigenetic repression of type I IFN response genes in human papillomavirus (HPV)-negative HNSCC cells, and Smyd3 depletion using anti-sense oligonucleotides (ASOs) increases the sensitivity of syngeneic mouse oral carcinoma (MOC1) models to anti-PD-1 therapy. In this study, we utilized single-cell RNA-seq of MOC1 tumors treated with Smyd3 ASOs and found enrichment of type I IFN response pathways in cancer cells, a shift of CD8 T-cells toward an activated/memory phenotype, and a shift of neutrophils toward an anti-tumorigenic phenotype. Mechanisms of resistance to the Smyd3 ASO and anti-PD-1 combination were derived from cancer cells, macrophages, and CD8 T-cells, including neutrophil enrichment through the upregulation of , repression of and defective antigen presentation.

New reports of pathogen spectrum associated with bulb rot and their interactions during the development of rot in tulip.

Bulb rot, a highly damaging disease of tulip plants, has hindered their profitable cultivation worldwide. This rot occurs in both field and storage conditions posing significant challenges. While this disease has been attributed to a range of pathogens, previous investigations have solely examined it within the framework of a single-pathogen disease model.

Characterization of Pre-Breeding Wheat ( L.) Germplasm for Stripe Rust Resistance Using Field Phenotyping and Genotyping.

Wheat is highly affected by stripe rust disease, particularly under cooler environments, and the losses can reach up to 100 percent depending on the intensity of infection and the susceptibility of the genotype. The most effective method to manage this disease is the use of resistant varieties. In the present study, 192 wheat genotypes were evaluated for stripe rust resistance under field conditions and also in a laboratory using molecular markers.

SMYD3 represses tumor-intrinsic interferon response in HPV-negative squamous cell carcinoma of the head and neck.

Cancers often display immune escape, but the mechanisms are incompletely understood. Herein, we identify SMYD3 as a mediator of immune escape in human papilloma virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), an aggressive disease with poor response to immunotherapy with pembrolizumab. SMYD3 depletion induces upregulation of multiple type I interferon (IFN) response and antigen presentation machinery genes in HNSCC cells.

Genetic footprint of population diversity and genetic structure of infecting apple (Malus × domestica Borkh.).

Unlabelled: Apple scab instigated by impels remarkable losses to apple fruit production. In an effort to comprehend the key mechanisms of evolutionary potential defining population, 132 isolates of from five commercial apple orchards were collected and assayed using 14 microsatellite markers. The average diversity was observed within the individuals of populations based on the Shannon-Wieners index (I) and observed heterozygosity (Ho) was average but considerably lower than expected heterozygosity (He).

Dnmt3bas coordinates transcriptional induction and alternative exon inclusion to promote catalytically active Dnmt3b expression.

Embryonic expression of DNMT3B is critical for establishing de novo DNA methylation. This study uncovers the mechanism through which the promoter-associated long non-coding RNA (lncRNA) Dnmt3bas controls the induction and alternative splicing of Dnmt3b during embryonic stem cell (ESC) differentiation. Dnmt3bas recruits the PRC2 (polycomb repressive complex 2) at cis-regulatory elements of the Dnmt3b gene expressed at a basal level.

Probing the Site-Specific Reactivity and Catalytic Activity of Ag ( = 15-20) Silver Clusters.

Density functional theory calculations within the framework of generalized gradient approximation (GGA), meta-GGA, and local functionals were carried out to investigate the reactivity and catalytic activity of Ag ( = 15-20) clusters. Our results reveal that all the Ag clusters in this size range, except Ag, adsorb O preferably in the bridged mode with enhanced binding energy as compared to the atop mode. The O binding energies range from 0.

Identification of a stretch of four discontinuous amino acids involved in regulating kinase activity of IGF1R.

IGF1R is pursued as a therapeutic target because of its abnormal expression in various cancers. Recently, we reported the presence of a putative allosteric inhibitor binding pocket in IGF1R that could be exploited for developing novel anti-cancer agents. In this study, we examined the role of nine highly conserved residues surrounding this binding pocket, with the aim of screening compound libraries in order to develop small-molecule allosteric inhibitors of IGF1R.

RyR2/IRBIT regulates insulin gene transcript, insulin content, and secretion in the insulinoma cell line INS-1.

The role of ER Ca release via ryanodine receptors (RyR) in pancreatic β-cell function is not well defined. Deletion of RyR2 from the rat insulinoma INS-1 (RyR2) enhanced IP receptor activity stimulated by 7.5 mM glucose, coincident with reduced levels of the protein IP Receptor Binding protein released with Inositol 1,4,5 Trisphosphate (IRBIT).

First report of associated with the bulb rot of Tulip (Tulipa spp) in India.

Tulip is an ornamental bulbous flowering crop belonging to the Genus and family . It is the first ranking bulbous ornamental plant in the world (Nayeem and Qayoom 2015). They are often the first flowers to witness the bloom in the spring.

Transcriptome-wide identification of squalene epoxidase genes from Glycyrrhiza glabra L.: expression analysis and heterologous expression of GgSQE1 suggest important role in terpenoid biosynthesis.

Squalene epoxidase (SQE) is a crucial regulatory enzyme for the biosynthesis of several important classes of compounds including sterols and triterpenoids. The present paper identified and characterised five SQE genes (GgSQE1 to GgSQE5) from Glycyrrhiza glabra through transcriptome data mining and homology-based cloning, for the first time. The phylogenetic analysis implied their functional divergence.

Influence of domestication on specialized metabolic pathways in fruit crops.

During the process of plant domestication, the selection and traditional breeding for desired characters such as flavor, juiciness and nutritional value of fruits, probably have resulted in gain or loss of specialized metabolites contributing to these traits. Their appearance in fruits is likely due to the acquisition of novel and specialized metabolic pathways and their regulation, driven by systematic molecular evolutionary events facilitated by traditional breeding. Plants change their armory of specialized metabolism to adapt and survive in diverse ecosystems.

Differential Modulation in Metabolites Revealed with the Improvement in the Shelf-Life of Alphonso Fruits.

Globally farmers have difficulty in extending the shelf-life of the tropical fruits due to their perishable nature. The present study aimed to assess the effect of hexanal nano-formulation treatment (NFT) on the shelf-life of Alphonso mango. Further, volatilomics was performed to explore the molecular basis of such effect.

Oct4-Mediated Inhibition of Lsd1 Activity Promotes the Active and Primed State of Pluripotency Enhancers.

An aberrant increase in pluripotency gene (PpG) expression due to enhancer reactivation could induce stemness and enhance the tumorigenicity of cancer stem cells. Silencing of PpG enhancers (PpGe) during embryonic stem cell differentiation involves Lsd1-mediated H3K4me1 demethylation and DNA methylation. Here, we observed retention of H3K4me1 and DNA hypomethylation at PpGe associated with a partial repression of PpGs in F9 embryonal carcinoma cells (ECCs) post-differentiation.

Tweaking genome-editing approaches for virus interference in crop plants.

Plant viruses infect various economically important crops and cause a serious threat to agriculture. As of now, conventional strategies employed are inadequate to circumvent the proliferation of rapidly evolving plant viruses. In this regard, recent advancement in genome-editing approach looks promising to produce plants resistant to DNA/RNA virus infections.

Preoperative contrast-enhanced computed tomographic characterisation of pancreatic cystic lesions: A prospective study.

Background: Characterisation of pancreatic cystic lesions has a direct role in their management and computed tomography is the mainstay of investigation for diagnosing and characterising them.

Objectives: The aim of this study was to prospectively assess the diagnostic accuracy of contrast-enhanced computed tomography (CECT) in preoperative characterisation of pancreatic cystic lesions with histopathology as the reference standard.

Method: A total of 38 patients with cystic pancreatic lesions diagnosed after clinical, laboratory and sonographic evaluation, irrespective of age, were preoperatively evaluated with CECT.

Identification of dinactin, a macrolide antibiotic, as a natural product-based small molecule targeting Wnt/β-catenin signaling pathway in cancer cells.

Purpose: Despite the fact that hyper-activation of Wnt/β-catenin signaling pathway has been seen in many cancers, including liver, colorectal and lung carcinoma, no small molecule inhibitors are available that specifically target this pathway. In this study, we analyzed the impact of dinactin (DA), an antibiotic ionophore produced by Streptomyces species, as an effective small molecule targeting Wnt/β-catenin signaling pathway in cancer cells.

Methods: We performed MTT assays to investigate cell viability and proliferation after exposure to small molecules.

Effect of Disease-Associated Germline Mutations on Structure Function Relationship of DNA Methyltransferases.

Despite a large body of evidence supporting the role of aberrant DNA methylation in etiology of several human diseases, the fundamental mechanisms that regulate the activity of mammalian DNA methyltransferases (DNMTs) are not fully understood. Recent advances in whole genome association studies have helped identify mutations and genetic alterations of DNMTs in various diseases that have a potential to affect the biological function and activity of these enzymes. Several of these mutations are germline-transmitted and associated with a number of hereditary disorders, which are potentially caused by aberrant DNA methylation patterns in the regulatory compartments of the genome.

Identification of a unique loss-of-function mutation in IGF1R and a crosstalk between IGF1R and Wnt/β-catenin signaling pathways.

IGF1R is a ubiquitous receptor tyrosine kinase that plays critical roles in cell proliferation, growth and survival. Clinical studies have demonstrated upregulation of IGF1R mediated signaling in a number of malignancies including colon, breast, and lung cancers. Overexpression of the IGF1R in these malignancies is associated with a poor prognosis and overall survival.

Î’eta-catenin N-terminal domain: An enigmatic region prone to cancer causing mutations.

The Wnt/β-catenin is a highly conserved signaling pathway involved in cell fate decisions during various stages of development. Dysregulation of canonical Wnt/β-catenin signaling has been associated with various diseases including cancer. β-Catenin, the central component of canonical Wnt signaling pathway, is a multi-functional protein playing both structural and signaling roles.