Acute hibernation decreases myocardial pyruvate carboxylation and citrate release

In the well-perfused heart, pyruvate carboxylation accounts for 3-6% of the citric acid cycle (CAC) flux, and CAC carbon is lost via citrate release. We investigated the effects of an acute reduction in coronary flow on these processes and on the tissue content of CAC intermediates. Measurements were made in an open-chest anesthetized swine model. Left anterior descending coronary artery blood flow was controlled by a extracorporeal perfusion circuit, and flow was decreased by 40% for 80 min to induce myocardial hibernation (n = 8). An intracoronary infusion of [U-(13)C(3)]lactate and [U-(13)C(3)]pyruvate was given to measure the entry of pyruvate into the CAC through pyruvate carboxylation from the (13)C-labeled isotopomers of CAC intermediates. Compared with normal coronary flow, myocardial hibernation resulted in parallel decreases of 65% and 79% in pyruvate carboxylation and net citrate release by the myocardium, respectively, and maintenance of the CAC intermediate content. Elevation of the arterial pyruvate concentration by 1 mM had no effect. Thus a 40% decrease in coronary blood flow resulted in a concomitant decrease in pyruvate carboxylation and citrate release as well as maintenance of the CAC intermediates.     

Seasonal Differences in Extinction and Colonization Drive Occupancy Dynamics of an Imperilled Amphibian

A detailed understanding of the population dynamics of many amphibian species is lacking despite concerns about declining amphibian biodiversity and abundance. This paper explores temporal patterns of occupancy and underlying extinction and colonization dynamics in a regionally imperiled amphibian species, the Northern leopard frog (Lithobates pipiens) in Alberta. Our study contributes to elucidating regional occupancy dynamics at northern latitudes, where climate extremes likely have a profound effect on seasonal occupancy. The primary advantage of our study is its wide geographic scale (60,000 km²) and the use of repeat visual surveys each spring and summer from 2009–2013. We find that occupancy varied more dramatically between seasons than years, with low spring and higher summer occupancy. Between spring and summer, colonization was high and extinction low; inversely, colonization was low and extinction high over the winter. The dynamics of extinction and colonization are complex, making conservation management challenging. Our results reveal that Northern leopard frog occupancy was constant over the last five years and thus there is no evidence of decline or recovery within our study area. Changes to equilibrium occupancy are most sensitive to increasing colonization in the spring or declining extinction in the summer. Therefore, conservation and management efforts should target actions that are likely to increase spring colonization; this could be achieved through translocations or improving the quality or access to breeding habitat. Because summer occupancy is already high, it may be difficult to improve further. Nevertheless, summer extinction could be reduced by predator control, increasing water quality or hydroperiod of wetlands, or increasing the quality or quantity of summer habitat.     

Host plant‐related variation in thermal tolerance of Eldana saccharina

Understanding tolerance of thermal extremes by pest insects is essential for developing integrated management strategies, as tolerance traits can provide insights into constraints on activity and survival. A major question in thermal biology is whether thermal limits vary systematically with microclimate variation, or whether other biotic or abiotic factors can influence these limits in a predictable manner. Here, we report the results of experiments determining thermal limits to activity and survival at extreme temperatures in the stalk borer Eldana saccharina Walker (Lepidoptera: Pyralidae), collected from either Saccharum spp. hybrids (sugarcane) (Poaceae) or Cyperus papyrus L. (Cyperaceae) and then reared under standard conditions in the laboratory for 1–2 generations. Chill‐coma temperature (CT_min), critical thermal maximum (CT_max), lower lethal temperatures (LLT), and freezing temperature between E. saccharina collected from the two host plants were compared. CT_min and CT_max of E. saccharina moths collected from sugarcane were significantly lower than those from C. papyrus (CT_min = 2.8 ± 0.4 vs. 3.9 ± 0.4 °C; CT_max = 44.6 ± 0.1 vs. 44.9 ± 0.2 °C). By contrast, LLT of moths and freezing temperatures of pupae did not vary with host plant [LLT for 50% (LT₅₀) of the moth population, when collected from sugarcane: ?3.2 ± 0.5 °C, from C. papyrus: ?3.9 ± 0.8 °C]. Freezing temperatures of pupae collected from C. papyrus were ?18.0 ± 1.0 °C and of those from sugarcane ?17.5 ± 1.8 °C. The E. saccharina which experienced the lowest minimum temperature (in C. papyrus) did not have the lowest CT_min, although the highest estimate of CT_max was found in E. saccharina collected from C. papyrus and this was also the microsite which reported the highest maximum temperatures. These results therefore suggest that host plant may strongly mediate lower critical thermal limits, but not necessarily LLT or freezing temperatures. These results have significant implications for ongoing pest management and thermal biology of these and other insects.     

The dawning of a 'Golden era' in lantibiotic bioengineering

There are many examples of highly modified antimicrobial peptides in nature, many of which are non-ribosomally synthesized. However, the bacterial lantibiotics are produced as gene-encoded pre-peptides that are subsequently modified by dedicated enzyme systems to form extraordinarily potent inhibitors. Consequently, they are much more amenable to bioengineering which could lead to the generation of a new arsenal of potent antimicrobials. However, although bioengineering of these compounds has been underway for at least two decades, significant progress has only been reported in recent years. This review charts these recent developments which suggest that we are entering a 'Golden era' of lantibiotic bioengineering.     

Efflux pumps expression and its association with porin down-regulation and β-lactamase production among <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> causing bloodstream infections in Brazil

Background  

Multi-drug efflux pumps have been increasingly recognized as a major component of resistance in P. aeruginosa. We have investigated the expression level of efflux systems among clinical isolates of P. aeruginosa, regardless of their antimicrobial susceptibility profile.     

Aspidosperma (Apocynaceae) plant cytotoxicity and activity towards malaria parasites. Part II: experimental studies with Aspidosperma ramiflorum in vivo and in vitro

Several species of Aspidosperma plants are used to treat diseases in the tropics, including Aspidosperma ramiflorum, which acts against leishmaniasis, an activity that is experimentally confirmed. The species, known as guatambu-yellow, yellow peroba, coffee-peroba andmatiambu, grows in the Atlantic Forest of Brazil in the South to the Southeast regions. Through a guided biofractionation of A. ramiflorum extracts, the plant activity against Plasmodium falciparum was evaluated in vitro for toxicity towards human hepatoma G2 cells, normal monkey kidney cells and nonimmortalised human monocytes isolated from peripheral blood. Six of the seven extracts tested were active at low doses (half-maximal drug inhibitory concentration < 3.8 µg/mL); the aqueous extract was inactive. Overall, the plant extracts and the purified compounds displayed low toxicity in vitro. A nonsoluble extract fraction and one purified alkaloid isositsirikine (compound 5) displayed high selectivity indexes (SI) (= 56 and 113, respectively), whereas compounds 2 and 3 were toxic (SI < 10). The structure, activity and low toxicity of isositsirikine in vitro are described here for the first time in A. ramiflorum, but only the neutral and precipitate plant fractions were tested for activity, which caused up to 53% parasitaemia inhibition of Plasmodium berghei in mice with blood-induced malaria. This plant species is likely to be useful in the further development of an antimalarial drug, but its pharmacological evaluation is still required.     

Response of methanotrophic communities to afforestation and reforestation in New Zealand

Methanotrophs use methane (CH₄) as a carbon source. They are particularly active in temperate forest soils. However, the rate of change of CH₄ oxidation in soil with afforestation or reforestation is poorly understood. Here, soil CH₄ oxidation was examined in New Zealand volcanic soils under regenerating native forests following burning, and in a mature native forest. Results were compared with data for pasture to pine land-use change at nearby sites. We show that following soil disturbance, as little as 47 years may be needed for development of a stable methanotrophic community similar to that in the undisturbed native forest soil. Corresponding soil CH₄-oxidation rates in the regenerating forest soil have the potential to reach those of the mature forest, but climo-edaphic fators appear limiting. The observed changes in CH₄-oxidation rate were directly linked to a prior shift in methanotrophic communities, which suggests microbial control of the terrestrial CH₄ flux and identifies the need to account for this response to afforestation and reforestation in global prediction of CH₄ emission.     

Fatty acid oxidation and its impact on response of spontaneously hypertensive rat hearts to an adrenergic stress: benefits of a medium-chain fatty acid

The spontaneously hypertensive rat (SHR) is a model of cardiomyopathy characterized by a restricted use of exogenous long-chain fatty acid (LCFA) for energy production. The aims of the present study were to document the functional and metabolic response of the SHR heart under conditions of increased energy demand and the effects of a medium-chain fatty acid (MCFA; octanoate) supplementation in this situation. Hearts were perfused ex vivo in a working mode with physiological concentrations of substrates and hormones and subjected to an adrenergic stimulation (epinephrine, 10 microM). (13)C-labeled substrates were used to assess substrate selection for energy production. Compared with control Wistar rat hearts, SHR hearts showed an impaired response to the adrenergic stimulation as reflected by 1) a smaller increase in contractility and developed pressure, 2) a faster decline in the aortic flow, and 3) greater cardiac tissue damage (lactate dehydrogenase release: 1,577 +/- 118 vs. 825 +/- 44 mU/min, P < 0.01). At the metabolic level, SHR hearts presented 1) a reduced exogenous LCFA contribution to the citric acid cycle flux (16 +/- 1 vs. 44 +/- 4%, P < 0.001) and an enhanced contribution of endogenous substrates (20 +/- 4 vs. 1 +/- 4%, P < 0.01); and 2) an increased lactate production from glycolysis, with a greater lactate-to-pyruvate production ratio. Addition of 0.2 mM octanoate reduced lactate dehydrogenase release (1,145 +/- 155 vs. 1,890 +/- 89 mU/min, P < 0.001) and increased exogenous fatty acid contribution to energy metabolism (23.7 +/- 1.3 vs. 15.8 +/- 0.8%, P < 0.01), which was accompanied by an equivalent decrease in unlabeled endogenous substrate contribution, possibly triglycerides (11.6 +/- 1.5 vs. 19.0 +/- 1.2%, P < 0.01). Taken altogether, these results demonstrate that the SHR heart shows an impaired capacity to withstand an acute adrenergic stress, which can be improved by increasing the contribution of exogenous fatty acid oxidation to energy production by MCFA supplementation.