Quantitative structured illumination microscopy via a physical model-based background filtering algorithm reveals actin dynamics.

Despite the prevalence of superresolution (SR) microscopy, quantitative live-cell SR imaging that maintains the completeness of delicate structures and the linearity of fluorescence signals remains an uncharted territory. Structured illumination microscopy (SIM) is the ideal tool for live-cell SR imaging. However, it suffers from an out-of-focus background that leads to reconstruction artifacts.

Superresolution live-cell imaging reveals that the localization of TMEM106B to filopodia in oligodendrocytes is compromised by the hypomyelination-related D252N mutation.

Hypomyelination leukodystrophies constitute a group of heritable white matter disorders exhibiting defective myelin development. Initially identified as a lysosomal protein, the TMEM106B D252N mutant has recently been associated with hypomyelination. However, how lysosomal TMEM106B facilitates myelination and how the D252N mutation disrupts that process are poorly understood.

A small-molecule cocktail promotes mammalian cardiomyocyte proliferation and heart regeneration.

Zebrafish and mammalian neonates possess robust cardiac regeneration via the induction of endogenous cardiomyocyte (CM) proliferation, but adult mammalian hearts have very limited regenerative potential. Developing small molecules for inducing adult mammalian heart regeneration has had limited success. We report a chemical cocktail of five small molecules (5SM) that promote adult CM proliferation and heart regeneration.

Sparse deconvolution improves the resolution of live-cell super-resolution fluorescence microscopy.

A main determinant of the spatial resolution of live-cell super-resolution (SR) microscopes is the maximum photon flux that can be collected. To further increase the effective resolution for a given photon flux, we take advantage of a priori knowledge about the sparsity and continuity of biological structures to develop a deconvolution algorithm that increases the resolution of SR microscopes nearly twofold. Our method, sparse structured illumination microscopy (Sparse-SIM), achieves ~60-nm resolution at a frame rate of up to 564 Hz, allowing it to resolve intricate structures, including small vesicular fusion pores, ring-shaped nuclear pores formed by nucleoporins and relative movements of inner and outer mitochondrial membranes in live cells.

Novel Insight into the Potential Pathogenicity of Mitochondrial Dysfunction Resulting from PLP1 Duplication Mutations in Patients with Pelizaeus-Merzbacher Disease.

Among the hypomyelinating leukodystrophies, Pelizaeus-Merzbacher disease (PMD) is a representative disorder. The disease is caused by different types of PLP1 mutations, among which PLP1 duplication accounts for ∼70% of the mutations. Previous studies have shown that PLP1 duplications lead to PLP1 retention in the endoplasmic reticulum (ER); in parallel, recent studies have demonstrated that PLP1 duplication can also lead to mitochondrial dysfunction.

Mitochondria determine the sequential propagation of the calcium macrodomains revealed by the super-resolution calcium lantern imaging.

Despite the wide application of super-resolution (SR) microscopy in biological studies of cells, the technology is rarely used to monitor functional changes in live cells. By combining fast spinning disc-confocal structured illumination microscopy (SD-SIM) with loading of cytosolic fluorescent Ca indicators, we have developed an SR method for visualization of regional Ca dynamics and related cellular organelle morphology and dynamics, termed SR calcium lantern imaging. In COS-7 cells stimulated with ATP, we have identified various calcium macrodomains characterized by different types of Ca+ release from endoplasmic reticulum (ER) stores.

Endoplasmic Reticulum Stress Activation in Alport Syndrome Varies Between Genotype and Cell Type.

Alport syndrome is a hereditary progressive chronic kidney disease caused by mutations in type IV collagen genes . X-linked Alport syndrome (XLAS) is caused by mutations in the gene and is the most common form of Alport syndrome. A strong correlation between the type of mutation and the age developing end-stage renal disease in male patients has been found.