Effect of Yoga Breathing (Pranayama) on Exercise Tolerance in Patients with Chronic Obstructive Pulmonary Disease: A Randomized, Controlled Trial.

OBJECTIVE: Pulmonary rehabilitation improves exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). However, many patients do not have access to pulmonary rehabilitation programs. We hypothesized that an alternative to pulmonary rehabilitation to improve exercise tolerance is the practice of pranayama, or yoga breathing, which could be done independently at home. We also sought to determine whether yoga nonprofessionals could adequately teach pranayama to patients. DESIGN: Proof-of-concept, randomized, double-blind, controlled pilot trial. SETTINGS/LOCATION: Two academic pulmonary practices. SUBJECTS: Forty-three patients with symptomatic, moderate-to-severe COPD. INTERVENTIONS: Twelve weeks of pranayama plus education versus education alone. Two yoga professionals trained the research coordinators to conduct all pranayama teaching and monitored the quality of the teaching and the practice of pranayama by study participants. OUTCOME MEASURES: The primary outcome was a change in the 6-min walk distance (6MWD). Secondary outcomes included changes in lung function, markers of oxidative stress and systemic inflammation, and measures of dyspnea and quality of life. RESULTS: The 6MWD increased in the pranayama group (least square mean [95% confidence interval] = 28 m [-5 to 61]) and decreased in the control group (-15 m [-47 to 16]), with a nearly significant treatment effect (p = 0.06) in favor of pranayama. Pranayama also resulted in small improvements in inspiratory capacity and air trapping. Both groups had significant improvements in various measures of symptoms, but no overall differences in respiratory system impedance or markers of oxidative stress or systemic inflammation. CONCLUSION: This pilot study successfully demonstrated that pranayama was associated with improved exercise tolerance in patients with COPD. Lay personnel were able to adequately teach patients to practice pranayama. These results suggest that pranayama may have significant clinical benefits for symptomatic patients with COPD, a concept that needs to be confirmed in future, larger clinical trials.

An epigenetic mark generated by the incorporation of CENP-A into centromeric nucleosomes.

Mammalian centromeres are defined epigenetically. Although the physical nature of the epigenetic mark is unknown, nucleosomes in which CENP-A replaces histone H3 are at the foundation of centromeric chromatin. Hydrogen/deuterium exchange MS is now used to show that assembly into nucleosomes imposes stringent conformational constraints, reducing solvent accessibility in almost all histone regions by >3 orders of magnitude. Despite this, nucleosomes assembled with CENP-A are substantially more conformationally rigid than those assembled with histone H3 independent of DNA template. Substitution of the CENP-A centromere targeting domain into histone H3 to convert it into a centromere-targeted histone that can functionally replace CENP-A in centromere maintenance generates the same more rigid nucleosome, as does CENP-A. Thus, the targeting information directing CENP-A deposition at the centromere produces a structurally distinct nucleosome, supporting a CENP-A-driven self-assembly mechanism that mediates maintenance of centromere identity.

Molecular basis for substrate recognition by MTMR2, a myotubularin family phosphoinositide phosphatase.

Myotubularins, a large family of catalytically active and inactive proteins, belong to a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as physiological substrates. Here, by integrating crystallographic and deuterium-exchange mass spectrometry studies of human myotubularin-related protein-2 (MTMR2) in complex with phosphoinositides, we define the molecular basis for this unique substrate specificity. Phosphoinositide substrates bind in a pocket located on a positively charged face of the protein, suggesting an electrostatic mechanism for membrane targeting. A flexible, hydrophobic helix makes extensive interactions with the diacylglycerol moieties of substrates, explaining the specificity for membrane-bound phosphoinositides. An extensive H-bonding network and charge-charge interactions within the active site pocket determine phosphoinositide headgroup specificity. The conservation of these specificity determinants within the active, but not the inactive, myotubularins provides insight into the functional differences between the active and inactive members.