Academia Sinica

About: Academia Sinica is a facility organization based out in Taipei, Taiwan. It is known for research contribution in the topics: Population & Galaxy. The organization has 52086 authors who have published 65998 publications receiving 1728114 citations. The organization is also known as: Central Research Academy.

Receptor binding redefined by a structural switch in a mutant human insulin.

Abstract: CRYSTAL structures of insulin have been determined in various distinct forms1–5, the relevance of which to receptor recognition has long been the subject of speculation2,6,7. Recently the crystal structure of an inactive insulin analogue has been determined and, surprisingly, found to have a conformation identical to native insulin8,9. On this basis Dodson and colleagues have suggested that the known insulin crystal structures reflect an inactive conformation, and that a change in conformation is required for activity—specifically, the carboxy terminal residues of the B-chain are proposed to separate from the amino terminal residues of the A-chain8. Here we report the solution structure of an active insulin mutant7,10, determined by two-dimensional NMR, which supports this hypothesis. In the mutant, the carboxy terminal β-turn and β-strand of the B-chain are destabilized and do not pack across the rest of the molecule. We suggest that analogous detachment of the carboxy terminal region of the B-chain occurs in native insulin on binding to its receptor. Our finding that partial unfolding of the B-chain exposes an alternative protein surface rationalizes the receptor-binding properties of a series of anomalous insulin analogues7,11–13, including a mutant insulin associated with diabetes mellitus in man14,15.

The role of microRNAs in sensing nutrient stress

Abstract: Recent studies have demonstrated the novel functions of microRNAs (miRNAs) in regulating plant adaptive responses to nutrient stresses. Plant miRNAs usually down-regulate the abundance of their target mRNAs by post-transcriptional cleavage. miR395 and miR399 are up-regulated during sulphate and phosphate (Pi) deficiency, respectively. miR395 participates in sulphate assimilation and allocation via adjusting the expression of ATP sulphurylase (APS) and a sulphate transporter (AtSULTR2;1). Up-regulation of miR399 results in the down-regulation of UBC24 encoding a ubiquitin-conjugating E2 enzyme. Plants overexpressing miR399 or are defective in UBC24display Pi toxicity because of increased Pi uptake, enhanced root-to-shoot translocation and retention of Pi in the old leaves. This observation suggests that the miR399-mediated regulation of UBC24 expression is critical in Pi homeostasis. Moreover, the existence and conservation of miR395 and miR399 and their target genes among many plant species reveals the evolutionary importance of these miRNA-mediated nutrient stress responses.

Tracking the engraftment and regenerative capabilities of transplanted lung stem cells using fluorescent nanodiamonds.

Abstract: Lung stem/progenitor cells are potentially useful for regenerative therapy, for example in repairing damaged or lost lung tissue in patients. Several optical imaging methods and probes have been used to track how stem cells incorporate and regenerate themselves in vivo over time. However, these approaches are limited by photobleaching, toxicity and interference from background tissue autofluorescence. Here we show that fluorescent nanodiamonds, in combination with fluorescence-activated cell sorting, fluorescence lifetime imaging microscopy and immunostaining, can identify transplanted CD45(-)CD54(+)CD157(+) lung stem/progenitor cells in vivo, and track their engraftment and regenerative capabilities with single-cell resolution. Fluorescent nanodiamond labelling did not eliminate the cells' properties of self-renewal and differentiation into type I and type II pneumocytes. Time-gated fluorescence imaging of tissue sections of naphthalene-injured mice indicates that the fluorescent nanodiamond-labelled lung stem/progenitor cells preferentially reside at terminal bronchioles of the lungs for 7 days after intravenous transplantation.

State-specific correlation of coincident product pairs in the F + CD4 reaction.

Abstract: When a chemical reaction forms two molecular products, even if the state-resolved differential cross section (DCS) for each product is obtained individually, the coincident attributes of the coproducts are still lacking. We exploit a method that provides coincidence information by measuring the state-resolved, pair-correlated DCS. Exemplified by the reaction F + CD 4 → DF + CD 3 , a time-sliced ion velocity imaging technique was used to measure the velocity distribution of a state-selected CD 3 product and to reveal the information of the coincident DF in a state-correlated manner. The correlation of different product state pairs shows a striking difference, which opens up a new way to unravel the complexity of a polyatomic reaction.