In Vivo Imaging of Inflammatory Phagocytes

1. Download : Download high-res image (288KB)
2. Download : Download full-size image

Highlights? Inflammation status can be determined by luminol (acute) or lucigenin (chronic) ? Neutrophils mediate MPO-dependent luminol luminescence during acute inflammation ? Macrophages rely on Phox to produce lucigenin luminescence in chronic inflammation ? No need for ectopic expression of reporters using this imaging method     

Stable Isotope-Labeled Raman Imaging Reveals Dynamic Proteome Localization to Lipid Droplets in Single Fission Yeast Cells

1. Download : Download high-res image (190KB)
2. Download : Download full-size image

Highlights? Raman spectroscopy requires no dye probe but still enables molecular imaging ? Stable-isotope labeling distinguishes between existing and newly formed proteins ? Protein localization to lipid droplets has been revealed in fission yeast ? The colocalization phenomenon is associated with starvation     

Fragment Screening at Adenosine-A3 Receptors in Living Cells Using a Fluorescence-Based Binding Assay

1. Download : Download high-res image (129KB)
2. Download : Download full-size image

Highlights? Fluorescence-based competition binding assay for adenosine-A₁ and -A₃ receptors ? Fragment screen using receptors in the native membrane environment in living cells ? Lead compound identification and optimization from a commercial fragment library     

A Potent and Selective S1P1 Antagonist with Efficacy in Experimental Autoimmune Encephalomyelitis

1. Download : Download high-res image (191KB)
2. Download : Download full-size image

Highlights? S1P₁ antagonists were designed and optimized ? NIBR-0213 is a highly potent and selective S1P₁ antagonist ? NIBR-0213 induces long lasting reduction of lymphocyte counts in blood ? NIBR-0213 has comparable efficacy to fingolimod (FTY720) in a mouse EAE model     

Prohibitin Ligands in Cell Death and Survival: Mode of Action and Therapeutic Potential

1. Download : Download high-res image (359KB)
2. Download : Download full-size image

Highlights? Prohibitins regulate cell survival, metabolism, and inflammation ? Prohibitins act as a hub for many signaling pathways ? Prohibitin ligands are examined in cancer, Parkinson’s disease, and obesity     

Identification of JadG as the B Ring Opening Oxygenase Catalyzing the Oxidative C-C Bond Cleavage Reaction in Jadomycin Biosynthesis

1. Download : Download high-res image (311KB)
2. Download : Download full-size image

Highlights? JadG catalyzes the oxidative C-C bond B ring cleavage of dehydrorabelomycin ? JadG needs FMNH₂ or FADH₂ as cofactors ? JadY is a flavin reductase that could supply FMNH₂ or FADH₂ for JadG     

A Competitive Stapled Peptide Screen Identifies a Selective Small Molecule that Overcomes MCL-1-Dependent Leukemia Cell Survival

1. Download : Download high-res image (218KB)
2. Download : Download full-size image

Highlights? A stapled peptide-based screen identified a selective molecular inhibitor of MCL-1 ? MIM1 targets a subregion of the BH3-binding pocket of antiapoptotic MCL-1 ? In contrast to ABT-737, MIM1 binds and functionally neutralizes MCL-1 but not BCL-X_L ? MIM1 exhibits MCL-1-dependent antileukemia activity and synergizes with ABT-737     

A fluorogenic red fluorescent protein heterodimer

1. Download : Download high-res image (518KB)
2. Download : Download full-size image

Highlights? A dimerization-dependent red fluorescent protein (ddRFP) was engineered ? ddRFP fluorogenesis results from modulation of pK_a and quantum yield ? ddRFP-based biosensors exhibit reversible intensiometric responses ? ddRFP-based biosensors can detect Ca²⁺ dynamics and caspase-3 activity in live cells     

The Antimalarial Natural Product Symplostatin 4 Is a Nanomolar Inhibitor of the Food Vacuole Falcipains

1. Download : Download high-res image (486KB)
2. Download : Download full-size image

Highlights? A convergent chemical synthesis of symplostatin 4 (Sym4) and Sym4 derivatives is reported ? Sym4 irreversibly inhibits malarial falcipains in infected red blood cells ? Sym4's unusual methyl-methoxypyrrolinone group is required for nanomolar inhibition of falcipains     

A Synthetic Substrate of DNA Polymerase Deviating from the Bases,Sugar, and Leaving Group of Canonical Deoxynucleoside Triphosphates

1. Download : Download high-res image (116KB)
2. Download : Download full-size image

Highlights? A highly modified nucleotide as substrate for polymerases ? The reversibility of the polymerase reaction at the template level ? Synthesis of a nucleoside with two anomeric centers     

Reconstitution of Nucleosome Demethylation and Catalytic Properties of a Jumonji Histone Demethylase

1. Download : Download high-res image (283KB)
2. Download : Download full-size image

Highlights? Catalytic domain of JMJD2A (cJMJD2A) removes methyl marks in a distributive manner ? Homogeneously methylated nucleosomes were used as substrates ? Quantitative assay for nucleosome demethylation has been developed     

Identification of exosite-targeting inhibitors of anthrax lethal factor by high-throughput screening

1. Download : Download high-res image (166KB)
2. Download : Download full-size image

Highlights? Development of an assay for LF protease using a full-length protein substrate ? Lichen depsidones identified as exosite-targeting LF inhibitors ? Exosite inhibitors protect macrophages from LF cytotoxicity     

Fluorescence Imaging of Single-Copy DNA Sequences within the Human Genome Using PNA-Directed Padlock Probe Assembly

1. Download : Download high-res image (135KB)
2. Download : Download full-size image

Highlights? PNA-directed assembly of the labeling complex on duplex DNA ? Padlock probes combined with rolling circle amplification for signal amplification ? Multitarget visualization within the human genome with high sequence selectivity     

Development of Antibiotic Activity Profile Screening for the Classification and Discovery of Natural Product Antibiotics

1. Download : Download high-res image (165KB)
2. Download : Download full-size image

Highlights? Antibiotics can be classified by structural class based on biological fingerprints ? BioMAP predicts the presence of known compounds in natural product extracts ? BioMAP reveals compounds with unique antibacterial properties ? A naphthoquinone antibiotic with a unique carbon skeleton has been discovered     

Interplay between the Ribosomal Tunnel,Nascent Chain,and Macrolides Influences Drug Inhibition

1. Download : Download high-res image (181KB)
2. Download : Download full-size image

Highlights? Macrolides exhibit nascent polypeptide chain–dependent inhibition ? Peptides can form specific interactions with the ribosomal tunnel ? A covalent bond between tylosin and the ribosome is necessary for inhibitory activity     

Structural and functional investigation of the intermolecular interaction between NRPS adenylation and carrier protein domains

1. Download : Download high-res image (278KB)
2. Download : Download full-size image

Highlights? Crystallographic structure of NRPS adenylation and PCP domain interface ? NRPS adenylation C-terminal domain rotation creates appropriate PCP interface ? Mechanism-based inhibitor traps conformationally flexible proteins ? Structure-guided mutagenesis improves noncognate NRPS interactions     

A LOV2 Domain-Based Optogenetic Tool to Control Protein Degradation and Cellular Function

1. Download : Download high-res image (288KB)
2. Download : Download full-size image

Highlights? Optogenetic tool to control the stability of soluble and membrane proteins ? Engineered using the LOV2 domain and a murine ornithine decarboxylase-like degron ? Creation of light-switchable, conditional mutants ? Graded response to very low blue light intensities allows yeast photography     

A Yeast Chemical Genetic Screen Identifies Inhibitors of Human Telomerase

1. Download : Download high-res image (173KB)
2. Download : Download full-size image

Highlights? Growth arrest induced by human telomerase in yeast is chemically reversible ? Readout is sensitive to telomerase catalytic activity and telomere recruitment ? Three cell-permeable compounds also inhibit purified human telomerase ? Yeast can be successfully used to screen for human telomerase inhibitors     

Orthogonal Ubiquitin Transfer through Engineered E1-E2 Cascades for Protein Ubiquitination

1. Download : Download high-res image (237KB)
2. Download : Download full-size image

Highlights? Orthogonal ubiquitin (UB) transfer pathway to synthesize specific UB-E2 conjugates ? Phage display to engineer UB-E1 and UB-E2 interactions ? Engineered xUB-xE1 and xE1-xE2 pairs with no cross-reactivities with native enzymes     

Picoliter cell lysate assays in microfluidic droplet compartments for directed enzyme evolution

1. Download : Download high-res image (187KB)
2. Download : Download full-size image

Highlights? Microfluidic droplet compartments miniaturize cell lysate screening assays ? Picoliter single-cell lysate assays comparable in sensitivity to macroscale ? Directed evolution results in improved clones validating this experimental set-up ? Precision of droplet sorting enables enrichment of clones with slight improvements