polyethyleneimine-coated-iron-oxide-nanoparticles-as-vehicle-for

Polyethyleneimine-coated Iron Oxide Nanoparticles as a Vehicle for the Delivery of Small Interfering RNA to Macrophages <em>In Vitro</em> and <em>In Vivo</em>

Because of their critical role in regulating immune responses, macrophages have continuously been the subject of intensive research and represent a ...

Southeast University

Subunit-subunit interactions of the classical and alternate chaperone-usher (CU) systems have been shown to proceed through a donor strand exchange (DSE) mechanism. However, it is not known whether DSE is required for intersubunit interactions in the archaic CU system. We have previously shown that the Myxococcus xanthus Mcu system, a member of the archaic CU family that functions in spore coat formation, is likely to use the principle of donor strand complementation to medicate chaperone-subunit interactions analogous to the classical CU pathway. Here we describe the results of studies on Mcu subunit-subunit interactions. We constructed a series of N-terminal-deleted, single amino acid-mutated and donor strand-complemented Mcu subunits, and characterized their abilities to participate in subunit-subunit interactions. It appears that certain residues in both the N and C termini of McuA, a subunit of the Mcu system, play a critical role in intersubunit interactions and these interactions may involve the general principle of DSE of the classical and alternate CU systems. In addition, the specificity of the M. xanthus CU system for Mcu subunits over other spore coat proteins is demonstrated. 

The archaic chaperone-usher pathways may depend on donor strand exchange for intersubunit interactions.

Gene clusters coding for the chaperone/usher (CU) pathway are widely distributed in many important environmental and pathogenic microbes; however, information about the regulatory machineries controlling CU gene expression during multicellular morphogenesis is missing. The Myxococcus xanthus Mcu system, encoded by the mcuABCD gene cluster, represents a prototype of the archaic CU family that functions in spore coat formation. Using genome-wide transposon mutagenesis, we identified MXAN2872 to be a potential regulator of the mcuABC operon and demonstrated the necessity of MXAN2872 for mcuABC expression and fruiting body morphogenesis in early development. In silico, biochemical, and genetic analyses suggest that MXAN2872 encodes a Baeyer-Villiger monooxygenase (BVMO) of flavoproteins, and the potential cofactor-binding site as well as the BVMO fingerprint sequence is important for the regulatory role of the MXAN2872 protein. The expression profile of mcuA in strains with an MXAN2872 deletion and point mutation agrees well with the timing of cell aggregation of these mutants. Furthermore, McuA could not be detected either in a fruA-null mutant, where starvation-induced aggregation was completely blocked, or in the glycerol-induced spores, where sporulation was uncoupled from cell aggregation. In sum, the present work uncovers a positive role for MXAN2872, a metabolic enzyme-encoding gene, in controlling M. xanthus development. MXAN2872 functions by affecting the onset of cell aggregation, thereby leading to a secondary effect on the timing of mcuABC expression of this model organism.

Identification of a putative flavin adenine dinucleotide-binding monooxygenase as a regulator for Myxococcus xanthus development.

The nuclear factor-κB (NF-κB) family of transcription factors play an essential role for the regulation of inflammatory responses, immune function and malignant transformation. Aberrant activity of this signalling pathway may lead to inflammation, autoimmune diseases and oncogenesis. Over the last two decades great progress has been made in the understanding of NF-κB activation and how the response is counteracted for maintaining tissue homeostasis. Therapeutic targeting of this pathway has largely remained ineffective due to the widespread role of this vital pathway and the lack of specificity of the therapies currently available. Besides regulatory proteins and microRNAs, long non-coding RNA (lncRNA) is emerging as another critical layer of the intricate modulatory architecture for the control of the NF-κB signalling circuit. In this paper we focus on recent progress concerning lncRNA-mediated modulation of the NF-κB pathway, and evaluate the potential therapeutic uses and challenges of using lncRNAs that regulate NF-κB activity.

Xiaohua Mao

Key Laboratory of Ministry of Education for Developmental Genes & Human Diseases,
Institute of Life Sciences and School of Medicine,
Key Laboratory of Ministry of Education for Developmental Genes & Human Diseases, Institute of Life Sciences and School of Medicine

Southeast University

Polyethyleneimine-coated Iron Oxide Nanoparticles as a Vehicle for the Delivery of Small Interfering RNA to Macrophages In Vitro and In Vivo