Download Highlight Bola
Dierdre Roussin
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The synthesis and trafficking of iron-sulfur (Fe-S) clusters in both prokaryotes and eukaryotes requires coordination within an expanding network of proteins that function in the cytosol, nucleus, mitochondria, and chloroplasts in order to assemble and deliver these ancient and essential cofactors to a wide variety of Fe-S-dependent enzymes and proteins. This review focuses on the evolving roles of two ubiquitous classes of proteins that operate in this network: CGFS glutaredoxins and BolA proteins. Monothiol or CGFS glutaredoxins possess a Cys-Gly-Phe-Ser active site that coordinates an Fe-S cluster in a homodimeric complex. CGFS glutaredoxins also form [2Fe-2S]-bridged heterocomplexes with BolA proteins, which possess an invariant His and an additional His or Cys residue that serve as cluster ligands. Here we focus on recent discoveries in bacteria, fungi, humans, and plants that highlight the shared and distinct roles of CGFS glutaredoxins and BolA proteins in Fe-S cluster biogenesis, Fe-S cluster storage and trafficking, and Fe-S cluster signaling to transcriptional factors that control iron metabolism--.
The All Progressives Congress presidential candidate, on Thursday, released an 80-page policy document that highlights an eight-point agenda.The PUNCH reports that top on his priority lists of action plans was national security, economy, agriculture, power, oil and gas, transportation and education.In the manifesto exclusively obtained by The PUNCH on Friday, Tinubu said his objective is to foster a new society based on shared prosperity, tolerance, compassion, and the unwavering commitment to treating each citizen with equal respect and due regard.Here are 10 promises of the former Lagos State governor contained in the manifesto. 1. Build a Nigeria, especially for our youth, where sufficient jobs with decent wages create a better life.2. Manufacture, create, and invent more of the goods and services we require. Nigeria shall be known as a nation of creators, not just of consumers.3. Export more and import less, strengthening both the naira and our way of life. (adsbygoogle = window.adsbygoogle []).push();
By employing bola-amphiphilic dendrimers, we achieved superior performance in siRNA delivery with the second-generation dendrimer, whereas the third-generation dendrimer showed excellent DNA delivery. We systematically investigated these dendrimers in terms of cargo binding, cellular uptake, endosomal release, and in vivo delivery. The differences in size between the dendrimers and their nucleic acid cargos affected the cooperative multivalent interactions for cargo/vector binding and release, resulting in adaptive and selective cargo delivery. Furthermore, both dendrimers capitalized on the advantages of lipid and polymer vectors, while also providing tumor-targeting capabilities based on nanotechnology and redox-responsive cargo release. Notably, they enabled tumor- and cancer cell-specific delivery of siRNA and DNA therapeutics, leading to effective treatment in various cancer models, including aggressive and metastatic malignancies. These dendrimers outperformed currently available vectors. This study will inspire further exploitation of tailor-made dendrimer platforms for the cargo-selective delivery of various therapeutics in precision medicine.
Bola-amphiphilic dendrimers for cargo-specific nucleic acid delivery. (A) Chemical structures of the bola-amphiphilic dendrimers bola2A, bola4A, and bola8A studied in this work. (B) Cartoon illustration of bola-amphiphilic dendrimers bola4A and bola8A for cargo-selective and adaptive delivery of the two distinct nucleic acid types, DNA and siRNA.