ALBERT

Description: The effective and efficient removal of the BF 2 moiety from F -BODIPY derivatives has been achieved using two common Brønsted acids; treatment with trifluoroacetic acid (TFA) or methanolic hydrogen chloride (HCl) followed by work-up with Ambersep ® 900 resin (hydroxide form) effects this conversion in near-quantitative yields. Compared to existing methods, these conditions are relatively mild and operationally simple, requiring only reaction at room temperature for six hours (TFA) or overnight (HCl). Beilstein J. Org. Chem. 2015, 11, 37–41. doi:10.3762/bjoc.11.6

Description: We provide evidence that citrate anions bridge between mineral platelets in bone and hypothesize that their presence acts to maintain separate platelets with disordered regions between them rather than gradual transformations into larger, more ordered blocks of mineral. To assess this hypothesis, we take as a model for a citrate...

Description: Degeneracy in the genetic code, which enables a single protein to be encoded by a multitude of synonymous gene sequences, has an important role in regulating protein expression, but substantial uncertainty exists concerning the details of this phenomenon. Here we analyse the sequence features influencing protein expression levels in 6,348 experiments using bacteriophage T7 polymerase to synthesize messenger RNA in Escherichia coli. Logistic regression yields a new codon-influence metric that correlates only weakly with genomic codon-usage frequency, but strongly with global physiological protein concentrations and also mRNA concentrations and lifetimes in vivo. Overall, the codon content influences protein expression more strongly than mRNA-folding parameters, although the latter dominate in the initial ~16 codons. Genes redesigned based on our analyses are transcribed with unaltered efficiency but translated with higher efficiency in vitro. The less efficiently translated native sequences show greatly reduced mRNA levels in vivo. Our results suggest that codon content modulates a kinetic competition between protein elongation and mRNA degradation that is a central feature of the physiology and also possibly the regulation of translation in E. coli.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boel, Gregory -- Letso, Reka -- Neely, Helen -- Price, W Nicholson -- Wong, Kam-Ho -- Su, Min -- Luff, Jon D -- Valecha, Mayank -- Everett, John K -- Acton, Thomas B -- Xiao, Rong -- Montelione, Gaetano T -- Aalberts, Daniel P -- Hunt, John F -- GM106372/GM/NIGMS NIH HHS/ -- R15 GM106372/GM/NIGMS NIH HHS/ -- U54-GM094597/GM/NIGMS NIH HHS/ -- England -- Nature. 2016 Jan 21;529(7586):358-63. doi: 10.1038/nature16509. Epub 2016 Jan 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences and Northeast Structural Genomics Consortium, 702 Fairchild Center, MC2434, Columbia University, New York, New York 10027, USA. ; CNRS UMR8261, Institut de Biologie Physico-Chimique, 13-rue Pierre et Marie Curie, 75005 Paris, France. ; Department of Molecular Biology and Biochemistry and Northeast Structural Genomics Consortium, Center for Advanced Biotechnology and Medicine, Rutgers, the State University of New Jersey, Piscataway, New Jersey 08854, USA. ; Department of Biochemistry, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, Piscataway, New Jersey 08854, USA. ; Department of Physics, Williams College, Williamstown, Massachusetts 01267, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26760206" target="_blank"〉PubMed〈/a〉

Description: Journal of Medicinal Chemistry DOI: 10.1021/acs.jmedchem.7b01569

Description: In protein–DNA interactions, particularly transcription factor (TF) and transcription factor binding site (TFBS) bindings, associated residue variations form patterns denoted as subtypes. Subtypes may lead to changed binding preferences, distinguish conserved from flexible binding residues and reveal novel binding mechanisms. However, subtypes must be studied in the context of core bindings. While solving 3D structures would require huge experimental efforts, recent sequence-based associated TF-TFBS pattern discovery has shown to be promising, upon which a large-scale subtype study is possible and desirable. In this article, we investigate residue-varying subtypes based on associated TF-TFBS patterns. By re-categorizing the patterns with respect to varying TF amino acids, statistically significant ( P values ≤ 0.005) subtypes leading to varying TFBS patterns are discovered without using TF family or domain annotations. Resultant subtypes have various biological meanings. The subtypes reflect familial and functional properties and exhibit changed binding preferences supported by 3D structures. Conserved residues critical for maintaining TF-TFBS bindings are revealed by analyzing the subtypes. In-depth analysis on the subtype pair PKV V IL-CA CG TG versus PKV E IL-CA GC TG shows the V/E variation is indicative for distinguishing Myc from MRF families. Discovered from sequences only, the TF-TFBS subtypes are informative and promising for more biological findings, complementing and extending recent one-sided subtype and familial studies with comprehensive evidence.

Description: We have previously shown that α-thalassemia mental retardation X-linked (ATRX) and histone H3.3 are key regulators of telomeric chromatin in mouse embryonic stem cells. The function of ATRX and H3.3 in the maintenance of telomere chromatin integrity is further demonstrated by recent studies that show the strong association of ATRX/H3.3 mutations with alternative lengthening of telomeres in telomerase-negative human cancer cells. Here, we demonstrate that ATRX and H3.3 co-localize with the telomeric DNA and associated proteins within the promyelocytic leukemia (PML) bodies in mouse ES cells. The assembly of these telomere-associated PML bodies is most prominent at S phase. RNA interference (RNAi)-mediated knockdown of PML expression induces the disassembly of these nuclear bodies and a telomere dysfunction phenotype in mouse ES cells. Loss of function of PML bodies in mouse ES cells also disrupts binding of ATRX/H3.3 and proper establishment of histone methylation pattern at the telomere. Our study demonstrates that PML bodies act as epigenetic regulators by serving as platforms for the assembly of the telomeric chromatin to ensure a faithful inheritance of epigenetic information at the telomere.