How Synergy of Actin Assembly-Disassembly and Myosin Motors Drives Cell Shape Changes

International audienc

nucGEMs probe the biophysical properties of the nucleoplasm

Abstract The cell interior is highly crowded and far from thermodynamic equilibrium. This environment can dramatically impact molecular motion and assembly, and therefore influence subcellular organization and biochemical reaction rates. These effects depend strongly on length-scale, with the least information available at the important mesoscale (10-100 nanometers), which corresponds to the size of crucial regulatory molecules such as RNA polymerase II. It has been challenging to study the mesoscale physical properties of the nucleoplasm because previous methods were labor-intensive and perturbative. Here, we report nuclear Genetically Encoded Multimeric nanoparticles (nucGEMs). Introduction of a single gene leads to continuous production and assembly of protein-based bright fluorescent nanoparticles of 40 nm diameter. We implemented nucGEMs in budding and fission yeast and in mammalian cell lines. We found differences in particle motility between the nucleus and the cytosol at the mesoscale, that mitotic chromosome condensation ejects nucGEMs from the nucleus, and that nucGEMs are excluded from heterochromatin and the nucleolus. nucGEMs enable hundreds of nuclear rheology experiments per hour, and allow evolutionary comparison of the physical properties of the cytosol and nucleoplasm

Rhinitis in subjects with work-exacerbated asthma.

OBJECTIVES: This study aimed at characterizing the nature, severity, and timing of nasal and ocular symptoms in subjects with work-exacerbated asthma (WEA). METHODS: Among the 363 subjects referred to a tertiary-care hospital for the investigation of work-related asthma symptoms, 105 subjects who demonstrated non-specific bronchial hyperresponsiveness to histamine, but a negative response to a specific inhalation challenge with the suspected occupational agent(s) were considered as having WEA. Their characteristics were compared with those of 172 subjects with occupational asthma (OA), ascertained by a positive response to a specific inhalation challenge. RESULTS: A high proportion of subjects with WEA (83%) and OA (90%) reported at least one nasal symptom at work. Sneezing/itching and rhinorrhea were more frequent in subjects with OA (78% and 70%, respectively) than in those with WEA (61%, p = 0.004 and 57%, p = 0.038, respectively), while post-nasal discharge was more common in WEA (30%) than in OA (18%, p = 0.019). Nasal symptoms were less severe in WEA (median [25th-75th percentiles] global severity score: 4 [2-6]) as compared to OA (5 [4-7], p < 0.001). Nasal symptoms preceded less frequently those of asthma in subjects with WEA (17%) than in subjects with OA (43%, p = 0.001). CONCLUSIONS: Nasal symptoms are highly prevalent in subjects with WEA, although their clinical pattern differs from that found in OA. Further investigations of the health and socio-economic impacts of upper airways symptoms in WEA are required to improve the understanding and management of this common condition