Understanding the role of chromatin remodeling in the regulation of circadian transcription in Drosophila.

Circadian clocks enable organisms to anticipate daily changes in the environment and coordinate temporal rhythms in physiology and behavior with the 24-h day-night cycle. The robust cycling of circadian gene expression is critical for proper timekeeping, and is regulated by transcription factor binding, RNA polymerase II (RNAPII) recruitment and elongation, and post-transcriptional mechanisms. Recently, it has become clear that dynamic alterations in chromatin landscape at the level of histone posttranslational modification and nucleosome density facilitate rhythms in transcription factor recruitment and RNAPII activity, and are essential for progression through activating and repressive phases of circadian transcription. Here, we discuss the characterization of the BRAHMA (BRM) chromatin-remodeling protein in Drosophila in the context of circadian clock regulation. By dissecting its catalytic vs. non-catalytic activities, we propose a model in which the non-catalytic activity of BRM functions to recruit repressive factors to limit the transcriptional output of CLOCK (CLK) during the active phase of circadian transcription, while the primary function of the ATP-dependent catalytic activity is to tune and prevent over-recruitment of negative regulators by increasing nucleosome density. Finally, we divulge ongoing efforts and investigative directions toward a deeper mechanistic understanding of transcriptional regulation of circadian gene expression at the chromatin level

Analysis of gas chromatography/mass spectrometry data for catalytic lignin depolymerization using positive matrix factorization

Various catalytic technologies are being developed to efficiently convert lignin into renewable chemicals. However, due to its complexity, catalytic lignin depolymerization often generates a wide and complex distribution of product compounds. Gas chromatography/mass spectrometry (GC-MS) is a common analytical technique to profile the compounds that comprise lignin depolymerization products. GC-MS is applied not only to determine the product composition, but also to develop an understanding of the catalytic reaction pathways and of the relationships among catalyst structure, reaction conditions, and the resulting compounds generated. Although a very useful tool, the analysis of lignin depolymerization products with GC-MS is limited by the quality and scope of the available mass spectral libraries and the ability to correlate changes in GC-MS chromatograms to changes in lignin structure, catalyst structure, and other reaction conditions. In this study, the GC-MS data of the depolymerization products generated from organosolv hybrid poplar lignin using a copper-doped porous metal oxide catalyst and a methanol/dimethyl carbonate co-solvent was analyzed by applying a factor analysis technique, positive matrix factorization (PMF). Several different solutions for the PMF model were explored. A 13-factor solution sufficiently explains the chemical changes occurring to lignin depolymerization products as a function of lignin, reaction time, catalyst, and solvent. Overall, seven factors were found to represent aromatic compounds, while one factor was defined by aliphatic compounds

The many-faced KSR1: a tumor suppressor in breast cancer

Emerging evidence supports the dual function of kinase suppressor of Ras 1 (KSR1) as an active kinase and a scaffold, although it has been extensively referred as a pseudokinase, due to the absence of key residues in its catalytic domain [1, 2]. As a scaffolding protein, KSR1 orchestrates the assembly of the protein kinases RAF, mitogen activated protein kinase (MAPK) kinase (MEK), and extracellular signal-regulated kinase (ERK) in the canonical Ras-RAF-MAPKs pathway, in a Ras-dependent manner or upon growth factor treatment [1, 3]. Conversely, structural and biochemical studies reveal that KSR1 is capable of phosphorylating MEK and more importantly, the catalytic activity of KSR is markedly increased when BRAF or inhibitor-bound CRAF is introduced in the complexes [1, 4, 5]. Such findings add complexity to th

Adatoms and nanoengineering of carbon

We present a new and general mechanism for inter-conversion of carbon structures via a catalytic exchange process, which operates under conditions of Frenkel pair generation. The mechanism typically lowers reaction barriers by a factor of four compared to equivilent uncatalysed reactions. We examine the relevance of this mechanism for fullerene growth, carbon onions and nanotubes, and dislocations in irradiated graphite.Comment: 3 Figures, 5 Page letter accepted for publication in Chemical Physics Letter

Robustness and modularity properties of a non-covalent DNA catalytic reaction

The biophysics of nucleic acid hybridization and strand displacement have been used for the rational design of a number of nanoscale structures and functions. Recently, molecular amplification methods have been developed in the form of non-covalent DNA catalytic reactions, in which single-stranded DNA (ssDNA) molecules catalyze the release of ssDNA product molecules from multi-stranded complexes. Here, we characterize the robustness and specificity of one such strand displacement-based catalytic reaction. We show that the designed reaction is simultaneously sensitive to sequence mutations in the catalyst and robust to a variety of impurities and molecular noise. These properties facilitate the incorporation of strand displacement-based DNA components in synthetic chemical and biological reaction networks

Electrocatalytic phenomena in gas phase reactions in solid electrolyte electrochemical cells

The recent literature on electrocatalysis and electrocatalytic phenomena occurring in gas phase reactions on solid, oxygen conducting electrolytes is reviewed. In this field there are a number of different subjects which are treated separately. These are: the use of electrochemical methods to study catalytic phenomena, electrocatalysis proper, the transfer of oxygen at the electrodes or electrolyte, and the (electro)catalytic properties of mixed, electronic and ionic, conducting materials

RpfC (Rv1884) atomic structure shows high structural conservation within the resuscitation promoting factor catalytic domain

We report the first structure of the catalytic domain of RpfC (Rv1884), one of theresuscitation-promoting factors (RPFs) from Mycobacterium tuberculosis. The structure was solved using molecular replacement, once the space group had been correctly identified as twinned P21 rather than the apparent C2221 by searching for anomalous scattering sites in P1. The structure displays a very high degree of structural conservation with the structures of the catalytic domains of RpfB (Rv1009) and RpfE (Rv2450) already published. This structural conservation highlights the importance of the versatile domain composition of the RPF family