Ribosomal RNA (rRNA) genes are down-regulated during osteogenesis, myogenesis, and adipogenesis, necessitating a mechanistic understanding of interrelationships between growth control and phenotype commitment. Here, we show that cell fate-determining factors [MyoD, myogenin (Mgn) , Runx2, C/EBP␤] occupy rDNA loci and suppress rRNA expression during lineage progression, concomitant with decreased rRNA expression and reciprocal loss of occupancy by c-Myc, a proliferation-specific activator of rRNA transcription. We find interaction of phenotypic factors with the polymerase I activator upstream binding factor UBF-1 at interphase nucleoli, and this interaction is epigenetically retained on mitotic chromosomes at nucleolar organizing regions. Ectopic expression and RNA interference establish that MyoD, Mgn, Runx2, and C/EBP␤ each functionally suppress rRNA genes and global protein synthesis. We conclude that epigenetic control of ribosomal biogenesis by lineage-specific differentiation factors is a general developmental mechanism for coordinate control of cell growth and phenotype.ibosomal biogenesis is directly linked to cell growth and proliferation (1). Actively dividing cells require continuous ribosome synthesis to ensure that progeny cells have the capacity to support protein synthesis after cell division. A control point in the complex process of ribosome biogenesis is the transcriptional regulation of ribosomal RNA (rRNA) genes, which are transcribed by the RNA polymerase I (pol I) machinery. Although regulation of ribosomal biogenesis during the cell cycle is well documented (2), mechanisms that interrelate control of protein synthesis and lineage commitment are minimally understood.Mesenchymal progenitor cells have the capacity to differentiate into cell lineages that include adipocytes, myoblasts, and osteoblasts (3). Phenotype determination requires integration of extracellular physiological cues and temporal up-regulation of cell type-specific regulatory proteins. During differentiation, cells undergo a phase of rapid proliferation and then withdraw from the cell cycle, concomitant with the expression of lineage-specific transcription factors. For example, osteoblast differentiation of mesenchymal progenitors requires induction of Runx2 (4, 5), whereas adipogenesis is regulated by sequential up-regulation of factors that include C/EBP (CCAAT/enhancer binding protein) -␤, -␦, and -␣ and peroxisome proliferator-activated receptor (PPAR) ␥ (reviewed in refs. 6 and 7). Similarly, the basic helix-loop-helix (bHLH) transcription factors MyoD and Myogenin (Mgn) play essential roles for skeletal muscle lineage determination by directly regulating RNA pol II-mediated muscle-specific genes (8-10). Withdrawal of proliferating progenitors and execution of differentiation programs coincide with a significant decrease in rRNA synthesis (11,12). One fundamental question is how RNA pol II-dependent phenotypic gene expression is coordinated with RNA pol I-mediated rRNA transcription during lineage commitment.In this stud...

The ongoing episode of coronavirus disease 19 has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a novel coronavirus known as SARS-CoV-2. The virus has an approximate 30 kb single-stranded positive-sense RNA genome, which is 74.5% to 99% identical to that of SARS-CoV, CoV-pangolin, and the coronavirus the from horseshoe bat. According to available information, SARS-CoV-2 is inferred to be a recombinant virus that originated from bats and was transmitted to humans, possibly using the pangolin as the intermediate host. The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. The serine protease inhibitors, spike protein-based vaccines, or ACE2 blockers may have therapeutic potential in the near future. At present, no vaccine is available against COVID-19. The disease is being treated with antiviral, antimalarial, anti-inflammatory, herbal medicines, and active plasma antibodies. In this context, the present review article provides a cumulative account of the recent information regarding the viral characteristics, potential therapeutic targets, treatment options, and prospective research questions.

Epigenetic control of ribosomal RNA (rRNA) gene transcription by cell type-specific regulators, such as the osteogenic transcription factor Runx2, conveys cellular memory of growth and differentiation to progeny cells during mitosis. Here, we examined whether coregulatory proteins contribute to epigenetic functions that are mitotically transmitted by Runx2 in osteoblastic cells. We show that the transcriptional corepressor Transducin Like Enhancer-1 (TLE1) associates with rRNA genes during mitosis and interphase through interaction with Runx2. Mechanistically, depletion of TLE1 relieves Runx2-mediated repression of rRNA genes transcription and selectively increases histone modifications linked to active transcription. Biologically, loss of TLE-dependent rRNA gene repression coincides with increased global protein synthesis and enhanced cell proliferation. Our findings reinforce the epigenetic marking target genes by phenotypic transcription factors in mitosis and demonstrate a requirement for retention of coregulatory factors to sustain physiological control of gene expression during proliferation of lineage committed cells.

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Cadmium resistant bacterium, isolated from industrial wastewater, was characterized as Salmonella enterica 43C on the basis of biochemical and 16S rRNA ribotyping. It is first ever reported S. enterica 43C bared extreme resistance against heavy metal consortia in order of Pb2+>Cd2+>As3+>Zn2+>Cr6+>Cu2+>Hg2+. Cd2+ stress altered growth pattern of the bacterium in time dependent manner. It could remove nearly 57 % Cd2+ from the medium over a period of 8 days. Kinetic and thermodynamic studies based on various adsorption isotherm models (Langmuir and Freundlich) depicted the Cd2+ biosorption as spontaneous, feasible and endothermic in nature. Interestingly, the bacterium followed pseudo first order kinetics, making it a good biosorbent for heavy metal ions. The S. enterica 43C Cd2+ processivity was significantly influenced by temperature, pH, initial Cd2+ concentration, biomass dosage and co-metal ions. FTIR analysis of the bacterium revealed the active participation of amide and carbonyl moieties in Cd2+ adsorption confirmed by EDX analysis. Electron micrographs beckoned further surface adsorption and increased bacterial size due to intracellular Cd2+ accumulation. An overwhelming increase in glutathione and other non-protein thiols levels played a significant role in thriving oxidative stress generated by metal cations. Presence of metallothionein clearly depicted the role of such proteins in bacterial metal resistance mechanism. The present study results clearly declare S. enterica 43C a suitable candidate for green chemistry to bioremediate environmental Cd2+.Electronic supplementary materialThe online version of this article (doi:10.1186/s13568-016-0225-9) contains supplementary material, which is available to authorized users.

Haemophilia A patients are treated by infusion of factor VIII (FVIII) concentrates, either prophylactically in order to avoid spontaneous haemorrhages or on demand to treat bleeds. Prophylactic treatment of severe haemophilia patients has

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Bacillus thuringiensis (Bt) is the most successful, environmentally-friendly, and intensively studied microbial insecticide. The major characteristic of Bt is the production of proteinaceous crystals containing toxins with specific activity against many pests including dipteran, lepidopteran, and coleopteran insects, as well as nematodes, protozoa, flukes, and mites. These crystals allow large quantities of the protein toxins to remain stable in the environment until ingested by a susceptible host. It has been previously established that 135 kDa Cry proteins have a crystallization domain at their C-terminal end. In the absence of this domain, Cry proteins often need helper proteins or other factors for crystallization. In this review, we classify the Cry proteins based on their requirements for crystallization.