A docking interaction study of the effect of critical mutations in ribonuclease a on protein-ligand binding

Enzymes with ribonucleolytic activity play a pivotal role in gene expression and cellular homeostasis by altering the levels of cellular RNA. Ribonuclease A has been the most well studied of such enzymes whose histidine residues (His12 and His119) play a crucial role in the catalytic mechanism of the protein. The ligands chosen for this study, 2′CMP and 3′CMP, act as competitive substrate analog inhibitors of this enzyme. Using molecular graphics software freely available for academic use, AutoDock and PyMol, we demonstrate that substitution of either histidine residue by alanine causes marked changes in the distances between these critical residues of the enzyme. The ligands in the docked conformation (particularly on mutation of His119 to Ala) compensate for the altered free energy and hydrogen bonding abilities in these new protein‐ligand complexes

Identity Elements of Archaeal tRNA

Features unique to a transfer-RNA are recognized by the corresponding tRNA-synthetase. Keeping this in view we isolate the discriminating features of all archaeal tRNA. These are our identity elements. Further, we investigate tRNA-characteristics that delineate the different orders of archaea

Short-Term Immunosuppression Promotes Engraftment of Embryonic and Induced Pluripotent Stem Cells

SummaryEmbryonic stem cells (ESCs) are an attractive source for tissue regeneration and repair therapies because they can be differentiated into virtually any cell type in the adult body. However, for this approach to succeed, the transplanted ESCs must survive long enough to generate a therapeutic benefit. A major obstacle facing the engraftment of ESCs is transplant rejection by the immune system. Here we show that blocking leukocyte costimulatory molecules permits ESC engraftment. We demonstrate the success of this immunosuppressive therapy for mouse ESCs, human ESCs, mouse induced pluripotent stem cells (iPSCs), human induced pluripotent stem cells, and more differentiated ESC/(iPSCs) derivatives. Additionally, we provide evidence describing the mechanism by which inhibition of costimulatory molecules suppresses T cell activation. This report describes a short-term immunosuppressive approach capable of inducing engraftment of transplanted ESCs and iPSCs, providing a significant improvement in our mechanistic understanding of the critical role costimulatory molecules play in leukocyte activation

tRNA-isoleucine-tryptophan Composite Gene

Transfer-RNA genes in archaea often have introns intervening between exon sequences. The structural motif at the boundary between exon and intron is the bulge-helix-bulge. Computational investigations of these boundary structures in H. marismortui lead us to propose that tRNA-isoleucine and tRNA-tryptophan genes are co-located. Precise insilico identification of the splice-sites on the bulges at the exon-intron boundaries conduce us to infer that a single intron-containing composite tRNA-gene can give rise to more than one gene produc.Comment: 15 pages, 3 figure

MicroRNome Analysis Unravels the Molecular Basis of SARS Infection in Bronchoalveolar Stem Cells

Severe acute respiratory syndrome (SARS), caused by the coronavirus SARS-CoV, is an acute infectious disease with significant mortality. A typical clinical feature associated with SARS is pulmonary fibrosis and associated lung failure. In the aftermath of the SARS epidemic, although significant progress towards understanding the underlying molecular mechanism of the infection has been made, a large gap still remains in our knowledge regarding how SARS-CoV interacts with the host cell at the onset of infection. The rapidly changing viral genome adds another variable to this equation. We have focused on a novel concept of microRNA (miRNA)–mediated host–virus interactions in bronchoalveolar stem cells (BASCs) at the onset of infection by correlating the “BASC–microRNome” with their targets within BASCs and viral genome. This work encompasses miRNA array data analysis, target prediction, and miRNA–mRNA enrichment analysis and develops a complex interaction map among disease-related factors, miRNAs, and BASCs in SARS pathway, which will provide some clues for diagnostic markers to view an overall interplay leading to disease progression. Our observation reveals the BASCs (Sca-1+ CD34+ CD45- Pecam-), a subset of Oct-4+ ACE2+ epithelial colony cells at the broncho-alveolar duct junction, to be the prime target cells of SARS-CoV infection. Upregulated BASC miRNAs-17*, -574-5p, and -214 are co-opted by SARS-CoV to suppress its own replication and evade immune elimination until successful transmission takes place. Viral Nucleocapsid and Spike protein targets seem to co-opt downregulated miR-223 and miR-98 respectively within BASCs to control the various stages of BASC differentiation, activation of inflammatory chemokines, and downregulation of ACE2. All these effectively accounts for a successful viral transmission and replication within BASCs causing continued deterioration of lung tissues and apparent loss of capacity for lung repair. Overall, this investigation reveals another mode of exploitation of cellular miRNA machinery by virus to their own advantage

Algorithm for pattern recognition in nano-sized archaea

Hidden patterns abound in genome sequences. Sophisticated mathematical algorithms spot them. As of now, several powerful tools exist for identification of transfer-RNA genes from genomes. These sometimes fail to identify when introns are at noncanonical sites. We discuss our approach to this problem of identification and apply it to the genome of Nanoarchaeum equitans. Using our algorithm, we identify the four tRNA genes that were missed by the present standard tRNA search programs in N. equitans. The recent split-tRNA hypothesis [Nature 433, 537 (2005)] identified the missing ones. However, our solutions are different. We argue the case in favour of our solutions.Author Affiliation: Jayprokas Chakrabarti, Satyabrata Sahoo, Bibekanand Mallick, Smarajit Das and Zhumur Ghosh 1.Computational Biology Group (CBG), Department of Theoretical Physics, Indian Association for the Cultivation of Science, Kolkata-700 032, India E-mail : [email protected] Biology Group (CBG), Department of Theoretical Physics, Indian Association for the Cultivation of Science, Kolkata-700 032, Indi