Impact of circadian time of dosing on cardiac-autonomous effects of glucocorticoids

Bioenergetic capacity is critical to adapt the high energy demand of the heart to circadian oscillations and diseased states. Glucocorticoids regulate the circadian cycle of energy metabolism, but little is known about how circadian timing of exogenous glucocorticoid dosing directly regulates cardiac bioenergetics through the primary receptor of these drugs, the glucocorticoid receptor (GR). While chronic once-daily intake of glucocorticoids promotes metabolic stress and heart failure, we recently discovered that intermittent once-weekly dosing of exogenous glucocorticoids promoted muscle metabolism and heart function in dystrophic mice. However, the effects of glucocorticoid intermittence on heart failure beyond muscular dystrophy remain unknown. Here we investigated the extent to which circadian time of dosing regulates the cardiac-autonomous effects of the glucocorticoid prednisone in conditions of single pulse or chronic intermittent dosing. In WT mice, we found that prednisone improved cardiac content of NAD+ and ATP with light-phase dosing (ZT0), while the effects were blocked by dark-phase dosing (ZT12). The effects on mitochondrial function were cardiomyocyte-autonomous, as shown by inducible cardiomyocyte-restricted GR ablation, and depended on an intact activating clock complex, as shown by hearts from BMAL1-KO mice. Conjugating time-of-dosing with chronic intermittence, we found that once-weekly light-phase prednisone improved metabolism and function in heart after myocardial injury. Our study identifies cardiac-autonomous mechanisms through which circadian time and chronic intermittence reconvert glucocorticoid drugs to bioenergetic boosters for the heart.

Generation of Hydrogen and Oxygen from Water by Solar Energy Conversion

Photosynthesis is considered to be one of the promising areas of cheap and environmentally friendly energy. Photosynthesis involves the process of water oxidation with the formation of molecular oxygen and hydrogen as byproducts. The aim of the present article is to review the energy (light) phase of photosynthesis based on the published X-ray studies of photosystems I and II (PS-I and PS-II). Using modern ideas about semiconductors and biological semiconductor structures, the mechanisms of H+, O2↑, e− generation from water are described. At the initial stage, PS II produces hydrogen peroxide from water as a result of the photoenzymatic reaction, which is oxidized in the active center of PS-II on the Mn4CaO5 cluster to form O2↑, H+, e−. Mn4+ is reduced to Mn2+ and then oxidized to Mn4+ with the transfer of reducing the equivalents of PS-I. The electrons formed are transported to PS-I (P 700), where the electrochemical reaction of water decomposition takes place in a two-electrode electrolysis system with the formation of gaseous oxygen and hydrogen. The proposed functioning mechanisms of PS-I and PS-II can be used in the development of environmentally friendly technologies for the production of molecular hydrogen.

Circadian Influences on Chemotherapy Efficacy in a Mouse Model of Brain Metastases of Breast Cancer

Chemotherapy is more effective in the treatment of peripheral tumors than brain metastases, likely reflecting the reduced ability of chemotherapy to cross the blood-brain barrier (BBB) and blood-tumor barrier at efficacious concentrations. Recent studies demonstrate circadian regulation of the BBB. Thus, we predicted that optimally timed chemotherapy would increase anti-tumor efficacy in a model of brain metastases of breast cancer (BMBC). First, we characterized novel daily alterations in BBB permeability to a commonly used chemotherapeutic, 14C-paclitaxel, within BMBC following injections given at four time points across the day. Peak and trough 14C-paclitaxel concentrations within BMBC occurred during the mid-dark phase and at the beginning of the light phase, respectively. Notably, chemotherapy injections during the dark phase increased cell death within BMBC and delayed onset of neurological symptoms relative to injections during the light phase. These data provide strong evidence for the beneficial effects of chrono-chemotherapy for the treatment of BMBC.

Algae-Assisted Microbial Desalination Cell: Analysis of Cathode Performance and Desalination Efficiency Assessment

Algae-assisted microbial desalination cells represent a sustainable technology for low-energy fresh water production in which microalgae culture is integrated into the system to enhance oxygen reduction reaction in the cathode chamber. However, the water production (desalination rate) is low compared to conventional technologies (i.e., reverse osmosis and/or electrodialysis), as biocathodes provide low current generation to sustain the desalination process. In this sense, more research efforts on this topic are necessary to address this bottleneck. Thus, this study provides analysis, from the electrochemical point of view, on the cathode performance of an algae-assisted microbial desalination cell (MDC) using Chlorella vulgaris. Firstly, the system was run with a pure culture of Chlorella vulgaris suspension in the cathode under conditions of an abiotic anode to assess the cathodic behavior (i.e., cathode polarization curves in light-dark conditions and oxygen depletion). Secondly, Geobacter sulfurreducens was inoculated in the anode compartment of the MDC, and the desalination cycle was carried out. The results showed that microalgae could generate an average of 9–11.5 mg/L of dissolved oxygen during the light phase, providing enough dissolved oxygen to drive the migration of ions (i.e., desalination) in the MDC system. Moreover, during the dark phase, a residual concentration of oxygen (ca. 5.5–8 mg/L) was measured, indicating that oxygen was not wholly depleted under our experimental conditions. Interestingly, the oxygen concentration was restored (after complete depletion of dissolved oxygen by flushing with N2) as soon as microalgae were exposed to the light phase again. After a 31 h desalination cycle, the cell generated a current density of 0.12 mA/cm2 at an efficiency of 60.15%, 77.37% salt was removed at a nominal desalination rate of 0.63 L/m2/h, coulombic efficiency was 9%, and 0.11 kWh/m3 of electric power was generated. The microalgae-assisted biocathode has an advantage over the air diffusion and bubbling as it can self-sustain a steady and higher concentration of oxygen, cost-effectively regenerate or recover from loss and sustainably retain the system’s performance under naturally occurring conditions. Thus, our study provides insights into implementing the algae-assisted cathode for sustainable desalination using MDC technology and subsequent optimization.

Spatial variability of physical, chemical and biological properties of agricultural soils in Hidalgo State, Mexico

The spatial distribution of physical, chemical and biological soil, affecting crop yields, however, the spatial dependence of soil biological parameters has been little explored. A study was conducted to establish the influence on soil fertility showed spatial variations of physical, chemical and biological properties of two agricultural soils in Hidalgo State (Mexico), belonging to the order Cambisol with low clay content activity. Soils A, (with a phase-clay-sandy, shallow horizon imperfect drainage), the municipality of Apan and soil B (with a light phase and thick, with stones), the municipality of Emiliano Zapata, were sampled in a network of 10x10m at 10, 20 and 40 cm deep. Were determined by physical, chemical and biological both soils. Geostatistical analyzes were performed using SPSS version 17.0. Texture, soil moisture and organic compounds changes affect the spatial distribution of the physical, chemical and biological properties of soils tested. The spatial variability of organic carbon, total nitrogen and C/N increased significantly with depth in the two soils, while the bulk density showed little spatial variation.

Circadian patterns of energy metabolism are only partially reconstituted in gnotobiotic mice

SUMMARYMicrobiota composition correlates with host metabolic health in both humans and mice. Here we investigated the extent to which a gnotobiotic microbiota can mimic the influence of a complete microbiota on mouse metabolism using an isolator-housed TSE-PhenoMaster® system. We found that energy expenditure was equivalent between germ-free (GF) and specific-opportunistic-pathogen free line (SPF) mice, and we extend this observation to the OligoMM12 microbiota (12 species across 5 phyla that are naturally abundant in a murine gut microbiota). Moreover, microbiota-released calories were well compensated by food intake in all groups. However, each group of mice have a distinctive circadian metabolic profile. OligoMM12 clustered with GF during the light phase, but with SPF during the dark phase for both RER and metabolome. Therefore, interactions between the host and a reductionist microbiota are non-uniform over the circadian cycle, revealing a promising tool to identify key microbiota species/functions that modify host metabolism.