Pancreatic ductal adenocarcinoma is the most common pancreatic neoplasm and as its name suggests it arises from ductal epithelial cells of the pancreas. Other subtypes of pancreatic neoplasms include benign and malignant cystic lesions, mucin producing tumor, acinar cell carcinoma, adenosquamous carcinoma, lymphomas and sarcomas. Pancreatic ductal adenocarcinoma evolves from a progressive cascade of cellular, morphological and architectural changes from normal ductal epithelium through preneoplastic lesions termed PanIN (Pancreatic Intraepithelial Neoplasia). These PanIN lesions are in turn associated with somatic alterations in canonical oncogenes and tumor suppressor genes. The molecular pathogenesis of human pancreatic ductal adenocarcinoma involves the temporal and[..]

During the course of transcription, the initial RNA product synthesized by RNA POL-II (RNA Polymerase-II), called a Primary transcript undergoes several processing steps including Capping, Splicing and Polyadenylation, before a functional mRNA (messenger RNA) is produced. RNA Polymerase initiates transcription at the first nucleotide of the first exon of a gene. Shortly after transcription begins, the 5' end of the nascent RNA is capped with 7-Methyl-Guanylate.Transcription by RNA polymerase-II terminates at any one of the multiple sites approx. 0.5-2kb downstream from the 3' end of the last exon in the transcript. The 3' end of a functional mRNA then is generated by endonucleolytic cleavage at a specific sequence, the Poly-A site, located at the 3' end[..]

Atherosclerosis is a chronic disease, the prevalence of which has increased steadily as the population ages. Vascular injury is believed to be critical initiating event in pathogenesis of spontaneous atherosclerosis. Economic development and urbanization have promoted habits of diet rich in saturated fat and diminished physical activity, which favors atherosclerosis. Traditionally two types of atherosclerosis are described, spontaneous and accelerated. Accelerated atherosclerosis mainly occurs in patients after heart transplant, CABG (coronary artery bypass graft), and PTCA (percutaneous transluminal coronary angioplasty) [Ref.1]. The normal artery contains three layers. The inner layer, the tunica intima, is lined by a monolayer of endothelial cells that is in contact[..]

The nuclei of all eukaryotic cells contain three different RNA Polymerases, designated I, II and III. Like the DNA polymerase that catalyzes DNA replication, RNA Polymerases catalyze the formation of the phosphodiester bonds that link the nucleotides together to form a linear chain. The RNA polymerase moves stepwise along the DNA, unwinding the DNA helix just ahead of the active site for polymerization to expose a new region of the template strand for complementary base-pairing. In this way, the growing RNA chain is extended by one nucleotide at a time in the 5’-to-3’ direction. The substrates are nucleoside triphosphates (ATP, CTP, UTP, and GTP); as for DNA replication, a hydrolysis of high-energy bonds provides the energy needed to drive the reaction[..]

The nuclei of all eukaryotic cells contain three different RNA Polymerases, designated I, II and III. Like the DNA Polymerase that catalyzes DNA replication, RNA Polymerases catalyze the formation of the phosphodiester bonds that link the nucleotides together to form a linear chain. Each eukaryotic RNA Polymerase catalyzes transcription of genes encoding different classes of RNA. RNA Polymerase-II catalyzes transcription of all protein-coding genes; that is, it functions in production of mRNAs. RNA Polymerase-II also produces four snRNAs (small nuclear RNAs) that take part in RNA splicing.The eukaryotic polymerases do not directly recognize their core promoter sequences. The first step in complex formation at a promoter containing a TATA Box is binding of the factor[..]

The nuclei of all eukaryotic cells contain three different RNA Polymerases, designated I, II and III. Like the DNA Polymerase that catalyzes DNA replication, RNA Polymerases catalyze the formation of the phosphodiester bonds that link the nucleotides together to form a linear chain. Each eukaryotic RNA Polymerase catalyzes transcription of genes encoding different classes of RNA. Transcription by RNA Polymerase-III produces small, stable RNAs including tRNAs, the 5S rRNA associated with the large ribosomal subunit, one of the snRNA (small nuclear RNAs) required for pre-mRNA splicing, and the 7S RNA associated with the signal recognition particle involved in secretion of proteins and the insertion of membrane-spanning proteins into cellular membranes. The func¬tions[..]

Splicing of pre-mRNA (pre-mRNA) is a complex mechanism where introns are removed, and exons are joined together to form a mature mRNA competent for translation. Pre-mRNA splicing is tightly regulated and its failure is linked to various tumors, pathologies of the endocrine system and neurodegenerative disorders. The discovery that introns are removed during splicing came from electron microscopy of RNA-DNA hybrids between adenovirus DNA and the mRNA encoding Hexon, a major virion capsid protein. For short transcription units, RNA splicing usually follows cleavage and polyadenylation of the 3’ end of the primary transcript. But for long transcription units containing multiple exons, splicing of exons in the nascent RNA usually begins before transcription of the[..]

ATP Binding Cassette transporters comprise a large family of membrane-spanning proteins that are responsible for transporting a variety of substrates in prokaryotes and eukaryotes. The most intriguing and, arguably, the most important membrane proteins for this purpose are the ABC (ATP-Binding Cassette) transporters. These proteins, found in all species, use the energy of ATP hydrolysis to translocate specific substrates across cellular membranes. Many of these transporters are responsible for the translocation of lipophilic substrates such as phospholipids, bile acids, and sterols (Ref.1 & 2).Beta-Sitosterol and other plant sterols are directly transported back to the gut lumen by the heterodimeric ABCG5-ABCG8 complex by means of a sort of kickback mechanism, which[..]

Biotin is a water-soluble vitamin found in all organisms that functions as a cofactor of Biotin-dependent carboxylases. It belongs to the B-Complex group of Vitamins and is an essential micronutrient for all mammals. The role of Biotin (or Vitamin-H) in Carboxylases is to act as vector for carboxyl-group transfer between donor and acceptor molecules during Carboxylation reaction (Ref.1). In M. musculus (Mus musculus), Biotin is a covalently bound as a prosthetic group in Biotin-dependent Carboxylases. It is covalently attached to Carboxylases by the action of Biotin-Protein Ligase. As a co-factor Biotin changes Apocarboxylases into active Holocarboxylases. For Biotin-Protein Ligase, Biotin addition occurs as an ATP-dependent, two-step reaction that, in the first[..]

Biotin is a water-soluble Vitamin required by all organisms by virtue of its essential role in carboxylation reactions. Whereas animals lack the ability to synthesize Biotin, it is synthesized by microorganisms and plants and therefore is widespread in the food supply at low concentrations relative to most water-soluble Vitamins (Ref.1). The highest level of Biotin occurs in organ meats such as liver and kidney, but it is low in meats, most vegetables, and fruits. It is also known as Vitamin-H. This member of Vitamin B-Complex group is colorless, withstands high temperatures and is orthorhombic when crystallized. It consists of two fused rings: an Imidazol (Ureido) and a Sulfur-containing (Tetrahydrothiophene) ring; and the latter is extended via a Valeric acid side[..]

Herpesviridae is a large family of viruses including several members that are pathogenic to humans, causing a variety of disorders ranging from cold sores and chicken pox to less frequent conditions such as blindness and cancers. HSV1 (Herpes Simplex Virus Type-1), the prototypical member of this family, is a large DNA-containing neurotropic virus endemic in all human populations. Following an initial infection in epithelial cells, the virus spreads to neurons of sensory ganglia, where it becomes latent. The virus emerges sporadically from latency, causing recurrent mucocutaneous lesions. Reactivation of the latent genomes upon stress can lead to re-infection of the epithelial tissue by anterograde spread or in immunosuppressed patients to life-threatening diseases[..]

GAs (Gibberellins) are members of a large family of Diterpenoid compounds, which are essential for a number of processes, including Gene Expression in Cereal Aleurones, Seed Germination, Elongation, Growth, and Flowering. During the last four decades, Barley Aleurone has been a valuable system for studying GA regulation of gene expression. After germination, GAs are released from the Embryo into the Endosperm, triggering the expression of a number of genes encoding Hydrolytic enzymes in Aleurone cells. Many of these Hydrolytic enzymes, which include Alpha-Amylase, Proteases, and Cell Wall–degrading enzymes, are secreted and are responsible for digestion of the stored reserves in the starchy endosperm. The Signal transduction events leading from the Receptor to[..]