Similarities and Differences among Protein Dynamics Studied by Variable Temperature Nuclear Magnetic Resonance Relaxation

Understanding and describing the dynamics of proteins is one of the major challenges in biology. Here, we use multifield variable-temperature NMR longitudinal relaxation (R-1) measurements to determine the hierarchical activation energies of motions of four different proteins: two small globular proteins (GB1 and the SH3 domain of alpha-spectrin), an intrinsically disordered protein (the C-terminus of the nucleoprotein of the Sendai virus, Sendai Ntail), and an outer membrane protein (OmpG). The activation energies map the motions occurring in the side chains, in the backbone, and in the hydration shells of the proteins. We were able to identify similarities and differences in the average motions of the proteins. We find that the NMR relaxation properties of the four proteins do share similar features. The data characterizing average backbone motions are found to be very similar, the same for methyl group rotations, and similar activation energies are measured. The main observed difference occurs for the intrinsically disordered Sendai Ntail, where we observe much lower energy of activation for motions of protons associated with the protein-solvent interface as compared to the others. We also observe variability between the proteins regarding side chain N-15 relaxation of lysine residues, with a higher activation energy observed in OmpG. This hints at strong interactions with negatively charged lipids in the bilayer and provides a possible mechanistic clue for the "positive-inside" rule for helical membrane proteins. Overall, these observations refine the understanding of the similarities and differences between hierarchical dynamics in proteins

Correlates of adherence to respiratory drugs in COPD patients

International audienceAIMS: To identify the correlates of accidental omissions and intentional interruptions of respiratory therapy in COPD. METHODS: COPD patients (GOLD stages II-IV) were recruited by general practitioners or respiratory physicians. Patients reported in self-report questionnaires their adherence to respiratory drugs (over the past three months) and their perception of therapy. RESULTS: 179 patients were included (mean age 63 years, 24% females). 45% forgot their respiratory therapy, while 30% interrupted it in the absence of any perceived benefit. The risks of accidental omissions were significantly higher when patients complained about having too many medications to take on a daily basis (OR=2.35; 95%CI=1.13-4.89), and among current smokers (OR=2.14; 95%CI=1.07-4.29). Females were more likely to interrupt therapy intentionally (OR=2.40; 95%CI=1.04-5.53). Surprisingly, there was no significant relationship with the number of drugs actually taken by patients. CONCLUSIONS: Adherence to respiratory drugs is inadequate in COPD patients. In order to improve adherence, patients' perception of the burden of therapy should not be overlooked

In situ analysis by SEM-EDX spectroscopy of 10 sarcoidosis cases from MINASARC study

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The Minasarc study: A case-control study measuring mineral exposome in sarcoidosis

International audienceIntroduction: it has been suggested that sarcoidosis could be associated with exposure to inorganic particles (Newman LS Curr Opin All Clin Immunol 2012; 12:145-50, Vincent M et al Am J Ind Med 2015; 58:S31-8).Objectives: in order to test this hypothesis the Minasarc study was designed to evaluate the mineral exposome by a specific questionnaire (SQ) and a mineralogical analysis performed on BALs by optical and electron microscopy in patients and healthy volunteers (HV). We present here the results obtained by the SQ which can be considered as a tool for global assessment of the “whole life” exposure to inorganic particles in occupational and environmental contexts.Methods: The study was performed on 20 patients with sarcoidosis and 20 HV. Every HV was matched to a patient by sex, age and smoking habit. The SQ was calibrated with a representative sample of the French population (n=825) in the ELIPSSilice survey (ANR-10-Eqpx-19-01) and the result was expressed as a “dust score”. Scores were compared by a Wilcoxon signed-rank test.Results: The “dust score” was found significantly higher in patients with sarcoidosis than in HV (p=0,036; Wilcoxon signed-rank test). Moreover we found a significant overrepresentation of people exposed to building activities among the cases. However this remains to be assessed on a larger series.Conclusion: The SQ demonstrated a significantly higher level of exposure to inorganic dusts in patients with sarcoidosis compared to HV. Such preliminary results encourage 1) to study the association between sarcoidosis and inorganic dust exposure and 2) to submit routinely this exposure questionnaire to every patient with a granulomatous disease

The Minasarc study: A case-control study measuring mineral exposome in sarcoidosis

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