Vasopressin V1 receptor‐mediated aldosterone production as a result of selective V2 receptor antagonism: a potential explanation for the failure of tolvaptan to reduce cardiovascular outcomes in the EVEREST trial

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106076/1/ejhfhfr150.pd

Domain Swapping and Different Oligomeric States for the Complex Between Calmodulin and the Calmodulin-Binding Domain of Calcineurin A

BACKGROUND: Calmodulin (CaM) is a ubiquitously expressed calcium sensor that engages in regulatory interactions with a large number of cellular proteins. Previously, a unique mode of CaM target recognition has been observed in the crystal structure of a complex between CaM and the CaM-binding domain of calcineurin A. METHODOLOGY/PRINCIPAL FINDINGS: We have solved a high-resolution crystal structure of a complex between CaM and the CaM-binding domain of calcineurin A in a novel crystal form, which shows a dimeric assembly of calmodulin, as observed before in the crystal state. We note that the conformation of CaM in this complex is very similar to that of unliganded CaM, and a detailed analysis revels that the CaM-binding motif in calcineurin A is of a novel '1-11' type. However, using small-angle X-ray scattering (SAXS), we show that the complex is fully monomeric in solution, and a structure of a canonically collapsed CaM-peptide complex can easily be fitted into the SAXS data. This result is also supported by size exclusion chromatography, where the addition of the ligand peptide decreases the apparent size of CaM. In addition, we studied the energetics of binding by isothermal titration calorimetry and found them to closely resemble those observed previously for ligand peptides from CaM-dependent kinases. CONCLUSIONS/SIGNIFICANCE: Our results implicate that CaM can also form a complex with the CaM-binding domain of calcineurin in a 1 ratio 1 stoichiometry, in addition to the previously observed 2 ratio 2 arrangement in the crystal state. At the structural level, going from 2 ratio 2 association to two 1 ratio 1 complexes will require domain swapping in CaM, accompanied by the characteristic bending of the central linker helix between the two lobes of CaM

Association between self-reported walking speed and calcaneal stiffness index in postmenopausal Japanese women

Background: Osteoporosis and related fractures, a worldwide public health issue of growing concern, is characterized by compromised bone strength and an increased risk of fracture. Here we show an association between self-reported walking speed and bone mass among community-dwelling postmenopausal Japanese women aged 50 years and older. Design; cross-sectional study: Setting and Participants; The survey population included 1008 postmenopausal women 50?92 years of age residing in rural communities. Methods: Self-reported walking speed was ascertained by asking the participants: “Is your walking speed faster than others of the same age and sex?” to which participants responded “yes (faster)” or “no (moderate/slower).” Calcaneal stiffness index was measured. Results: Women with a faster self-reported walking speed were younger and had a lower BMI, higher stiffness index, and higher grip strength than women with a slower walking speed. Multiple linear regression analysis adjusted for age, BMI, grip strength, comorbidity, current smoking, and alcohol drinking status showed a significant association between faster self-reported walking speed and higher calcaneal stiffness index (p < 0.001). Conclusions: Our findings suggest that questionnaires of walking speed may be useful for predicting bone mass and that a fast self-reported walking may benefit bone health in postmenopausal women

Factors Influencing the Preferred Place of Death in Community-dwelling Elderly People in Japan

Background: To investigate factors influencing the preferred place of death among community-living elderly people in Japan in relation to personal attributes, health status, self-rated health, and social capital indicators. Methods: A self-report questionnaire survey was conducted between July 2009 and September 2009 on a total of 238 elderly people aged ≥65 years living in Nagasaki Prefecture, Japan. Patients were either members of a social club for the elderly, individuals undergoing special health check-ups, or participants of health workshops held by cities. A total of 178 patients who provided complete responses (79 men, 99 women) were analyzed. Results: Half or more of the patients (men: 68.4%, women: 52.5%) indicated home as their preferred place of death. Multiple logistic regression analysis showed that good self-rated health [odds ratio (OR): 2.6, 95% confidence interval (95% CI): 1.2–5.7, p = 0.013], participation in volunteer activities (OR: 2.0, 95% CI: 1.0–3.8, p = 0.038) and the spouse as the preferred caregiver (OR: 2.5, 95% CI: 1.3–4.8, p = 0.007) were associated with home as the preferred place of death. Conclusion: It is necessary to consider individual preferences and public health strategies in order to enable elderly people to receive suitable and comfortable end-of-life care in their preferred location