Stimulation of oxidative phosphorylation by calcium in cardiac mitochondria is not influenced by cAMP and PKA activity

AbstractCardiac oxidative ATP generation is finely tuned to match several-fold increases in energy demand. Calcium has been proposed to play a role in the activation of ATP production via PKA phosphorylation in response to intramitochondrial cAMP generation. We evaluated the effect of cAMP, its membrane permeable analogs (dibutyryl-cAMP, 8-bromo-cAMP), and the PKA inhibitor H89 on respiration of isolated pig heart mitochondria. cAMP analogs did not stimulate State 3 respiration of Ca2+-depleted mitochondria (82.2±3.6% of control), in contrast to the 2-fold activation induced by 0.95μM free Ca2+, which was unaffected by H89. Using fluorescence and integrating sphere spectroscopy, we determined that Ca2+ increased the reduction of NADH (8%), and of cytochromes bH (3%), c1 (3%), c (4%), and a (2%), together with a doubling of conductances for Complex I+III and Complex IV. None of these changes were induced by cAMP analogs nor abolished by H89. In Ca2+-undepleted mitochondria, we observed only slight changes in State 3 respiration rates upon addition of 50μM cAMP (85±9.9%), dibutyryl-cAMP (80.1±5.2%), 8-bromo-cAMP (88.6±3.3%), or 1μM H89 (89.7±19.9%) with respect to controls. Similar results were obtained when measuring respiration in heart homogenates. Addition of exogenous PKA with dibutyryl-cAMP or the constitutively active catalytic subunit of PKA to isolated mitochondria decreased State 3 respiration by only 5–15%. These functional studies suggest that alterations in mitochondrial cAMP and PKA activity do not contribute significantly to the acute Ca2+ stimulation of oxidative phosphorylation

Optimizing Multi-Photon Fluorescence Microscopy Light Collection from Living Tissue by Non-Contact Total Emission Detection (TEDII)

Farrando Sicilia, Jordi; Fuente Fuente, Carlo

Ultra-Low Power on Skin ECG using RFID Communication

Electrocardiograms provide rhythm, rate and electrical activity of the heart which can be used to diagnose health issues. Current methodologies for wireless based heart monitoring favour the use of Bluetooth Low Energy, which can require bulky batteries for device longevity. This paper investigates the use of a novel ultra-low power communications technique utilising Ultra High Frequency Radio Frequency Identification to stream ECG data in real time to a host computer to enable sub 2mW power consumption

Health state preferences are equivalent in the United States and Trinidad and Tobago

To derive preference weights in Trinidad and Tobago for Quality of Well-being Scale (QWB) health states in order to calculate QWB scores that can be compared to scores calculated from US-derived preference weights. The comparison was to determine whether the QWB scores from these different preference weights would lead to similar conclusions. We conducted in-person household interviews to elicit preferences for 65 health states using a probability sample of 235 adults from Port of Spain, Chaguanas and San Fernando, Trinidad and Tobago. A regression model with correction for within-person clustering of observations was used to obtain preference weights based on case judgments on a 0 (dead) to 10 (“perfect health”) scale. The independent variables were the components of the QWB entered as indicator (0, 1) variables. One hundred and nineteen (51%) respondents provided ratings. The respondents that provided ratings were demographically no different from those that did not. The QWB response patterns were very similar using Trinidad and US weights. The mean (SD) QWB score was 0.750 (0.130) for female respondents and 0.784 (0.125) for male respondents using Trinidad coefficients (t 2, 233 = −2.05, P = 0.04) and 0.747 (0.131) for female respondents and 0.783 (0.126) for male respondents using US weights (t 2, 233 = −2.17, P = 0.03). Overall, we found the US and Trinidad and Tobago weights were highly similar and that the choice of either set of weights would lead to similar conclusions

Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration.

BACKGROUND: Obesity is associated with increased recurrence and reduced survival of breast cancer. Adipocytes constitute a significant component of breast tissue, yet their role in provisioning metabolic substrates to support breast cancer progression is poorly understood. RESULTS: Here, we show that co-culture of breast cancer cells with adipocytes revealed cancer cell-stimulated depletion of adipocyte triacylglycerol. Adipocyte-derived free fatty acids were transferred to breast cancer cells, driving fatty acid metabolism via increased CPT1A and electron transport chain complex protein levels, resulting in increased proliferation and migration. Notably, fatty acid transfer to breast cancer cells was enhanced from "obese" adipocytes, concomitant with increased stimulation of cancer cell proliferation and migration. This adipocyte-stimulated breast cancer cell proliferation was dependent on lipolytic processes since HSL/ATGL knockdown attenuated cancer cell responses. CONCLUSIONS: These findings highlight a novel and potentially important role for adipocyte lipolysis in the provision of metabolic substrates to breast cancer cells, thereby supporting cancer progression

Identifying Patients at High Risk of a Cardiovascular Event in the Near Future Current Status and Future Directions: Report of a National Heart, Lung, and Blood Institute Working Group

The National Heart, Lung, and Blood Institute convened a working group to provide basic and clinical research recommendations to the National Heart, Lung, and Blood Institute on the development of an integrated approach for identifying those individuals who are at high risk for a cardiovascular event such as acute coronary syndromes (ACS) or sudden cardiac death in the “near term.” The working group members defined near-term as occurring within 1 year of the time of assessment. The participants reviewed current clinical cardiology practices for risk assessment and state-of-the-science techniques in several areas, including biomarkers, proteomics, genetics, psychosocial factors, imaging, coagulation, and vascular and myocardial susceptibility. This report presents highlights of these reviews and a summary of suggested research directions