Central angiotensin II has catabolic action at white and brown adipose tissue

Considerable evidence implicates the renin-angiotensin system (RAS) in the regulation of energy balance. To evaluate the role of the RAS in the central nervous system regulation of energy balance, we used osmotic minipumps to chronically administer angiotensin II (Ang II; icv; 0.7 ng/min for 24 days) to adult male Long-Evans rats, resulting in reduced food intake, body weight gain, and adiposity. The decrease in body weight and adiposity occurred relative to both ad libitum- and pair-fed controls, implying that reduced food intake in and of itself does not underlie all of these effects. Consistent with this, rats administered Ang II had increased whole body heat production and oxygen consumption. Additionally, chronic icv Ang II increased uncoupling protein-1 and β(3)-adrenergic receptor expression in brown adipose tissue and β3-adrenergic receptor expression in white adipose tissue, which is suggestive of enhanced sympathetic activation and thermogenesis. Chronic icv Ang II also increased hypothalamic agouti-related peptide and decreased hypothalamic proopiomelanocortin expression, consistent with a state of energy deficit. Moreover, chronic icv Ang II increased the anorectic corticotrophin- and thyroid-releasing hormones within the hypothalamus. These results suggest that Ang II acts in the brain to promote negative energy balance and that contributing mechanisms include an alteration in the hypothalamic circuits regulating energy balance, a decrease in food intake, an increase in energy expenditure, and an increase in sympathetic activation of brown and white adipose tissue.     

The crystal structure of human GLRX5: iron-sulfur cluster co-ordination, tetrameric assembly and monomer activity

Human GLRX5 (glutaredoxin 5) is an evolutionarily conserved thiol-disulfide oxidoreductase that has a direct role in the maintenance of normal cytosolic and mitochondrial iron homoeostasis, and its expression affects haem biosynthesis and erythropoiesis. We have crystallized the human GLRX5 bound to two [2Fe-2S] clusters and four GSH molecules. The crystal structure revealed a tetrameric organization with the [2Fe-2S] clusters buried in the interior and shielded from the solvent by the conserved β1-α2 loop, Phe?? and the GSH molecules. Each [2Fe-2S] cluster is ligated by the N-terminal activesite cysteine (Cys??) thiols contributed by two protomers and two cysteine thiols from two GSH. The two subunits co-ordinating the cluster are in a more extended conformation compared with iron-sulfur-bound human GLRX2, and the intersubunit interactions are more extensive and involve conserved residues among monothiol GLRXs. Gel-filtration chromatography and analytical ultracentrifugation support a tetrameric organization of holo-GLRX5, whereas the apoprotein is monomeric. MS analyses revealed glutathionylation of the cysteine residues in the absence of the [2Fe-2S] cluster, which would protect them from further oxidation and possibly facilitate cluster transfer/acceptance. Apo-GLRX5 reduced glutathione mixed disulfides with a rate 100 times lower than did GLRX2 and was active as a glutathione-dependent electron donor for mammalian ribonucleotide reductase.     

Inhibition of suicidal erythrocyte death by blebbistatin

Blebbistatin, a myosin II inhibitor, interferes with myosin-actin interaction and microtubule assembly. By influencing cytoskeletal dynamics blebbistatin counteracts apoptosis of several types of nucleated cells. Even though lacking nuclei and mitochondria, erythrocytes may undergo suicidal cell death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Triggers of eryptosis include energy depletion and osmotic shock, which enhance cytosolic Ca(2+) activity with subsequent Ca(2+)-sensitive cell shrinkage and cell membrane scrambling. The present study explored the effect of blebbistatin on eryptosis. Cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, cell volume from forward scatter in fluorescence-activated cell sorting analysis and cytosolic Ca(2+) concentration from Fluo3 fluorescence. Exposure to blebbistatin on its own (1-50 μM) did not significantly modify cytosolic Ca(2+) concentration, forward scatter, or annexin V binding. Glucose depletion (48 h) was followed by a significant increase of Fluo3 fluorescence and annexin V binding, effects significantly blunted by blebbistatin (Fluo3 fluorescence ≥ 25 μM, annexin V binding ≥ 10 μM). Osmotic shock (addition of 550 mM sucrose) again significantly increased Fluo3 fluorescence and annexin binding, effects again significantly blunted by blebbistatin (Fluo3 fluorescence ≥ 25 μM, annexin V binding ≥ 25 μM). The present observations disclose a novel effect of blebbistatin, i.e., an influence on Ca(2+) entry and suicidal erythrocyte death following energy depletion and osmotic shock.     

Bioenergy potential of Ulva lactuca: biomass yield, methane production and combustion

The biomass production potential at temperate latitudes (56°N), and the quality of the biomass for energy production (anaerobic digestion to methane and direct combustion) were investigated for the green macroalgae, Ulva lactuca. The algae were cultivated in a land based facility demonstrating a production potential of 45 T (TS) ha⁻¹ y⁻¹. Biogas production from fresh and macerated U. lactuca yielded up to 271 ml CH₄ g⁻¹ VS, which is in the range of the methane production from cattle manure and land based energy crops, such as grass-clover. Drying of the biomass resulted in a 5-9-fold increase in weight specific methane production compared to wet biomass. Ash and alkali contents are the main challenges in the use of U. lactuca for direct combustion. Application of a bio-refinery concept could increase the economical value of the U. lactuca biomass as well as improve its suitability for production of bioenergy.     

Requirement of the agr locus for colony spreading of Staphylococcus aureus

The important human pathogen Staphylococcus aureus is known to spread on soft agar plates. Here, we show that colony spreading of S. aureus involves the agr quorum-sensing system. This finding can be related to the agr-dependent expression of biosurfactants, such as phenol-soluble modulins, suggesting a connection between spreading motility and virulence.     

Reduced immunoglobulin A transcytosis associated with immunoglobulin A nephropathy and nasopharyngeal carcinoma

Polymeric IgA (pIgA) is transcytosed by the pIgA receptor (pIgR) across mucosal epithelial cells. After transcytosis to the apical surface, the extracellular, ligand-binding portion of the pIgR is proteolytically cleaved. A missense mutation in human pIgR, A580V, is associated with IgA nephropathy and nasopharyngeal carcinoma. We report that this mutation reduces the rate of transcytosis of pIgR and pIgA, and seemingly the rate of pIgR cleavage. We propose that the defects in pIgR trafficking caused by the A580V mutation may underlie the pathogenesis of both diseases.     

Effects of recent warm and cold spells on European plant phenology

Climate change is already altering the magnitude and/or frequency of extreme events which will in turn affect plant fitness more than any change in the average. Although the fingerprint of anthropogenic warming in recent phenological records is well understood, the impacts of extreme events have been largely neglected. Thus, the temperature response of European phenological records to warm and cold spells was studied using the COST725 database. We restricted our analysis to the period 1951–2004 due to better spatial coverage. Warm and cold spells were identified using monthly mean ENSEMBLES temperature data on a 0.5° grid for Europe. Their phenological impact was assessed as anomalies from maps displaying mean onsets for 1930–1939. Our results clearly exhibit continental cold spells predominating in the period 1951–1988, especially during the growing season, whereas the period from 1989 onwards was mainly characterised by warm spells in all seasons. The impacts of these warm/cold spells on the onset of phenological seasons differed strongly depending on species, phase and timing. “False” phases such as the sowing of winter cereals hardly reacted to summer warm/cold spells; only the sowing of summer cereals mirrored spring temperature warm/cold spells. The heading dates of winter cereals did not reveal any consistent results probably due to fewer warm/cold spells identified in the relevant late spring months. Apple flowering and the harvest of winter cereals were the best indicators of warm/cold spells in early spring and summer, also being spatially coherent with the patterns of warm/cold spells.     

Tailored protection against plasmalemmal injury by annexins with different Ca2+ sensitivities

The annexins, a family of Ca(2+)- and lipid-binding proteins, are involved in a range of intracellular processes. Recent findings have implicated annexin A1 in the resealing of plasmalemmal injuries. Here, we demonstrate that another member of the annexin protein family, annexin A6, is also involved in the repair of plasmalemmal lesions induced by a bacterial pore-forming toxin, streptolysin O. An injury-induced elevation in the intracellular concentration of Ca(2+) ([Ca(2+)](i)) triggers plasmalemmal repair. The highly Ca(2+)-sensitive annexin A6 responds faster than annexin A1 to [Ca(2+)](i) elevation. Correspondingly, a limited plasmalemmal injury can be promptly countered by annexin A6 even without the participation of annexin A1. However, its high Ca(2+) sensitivity makes annexin A6 highly amenable to an unproductive binding to the uninjured plasmalemma; during an extensive injury accompanied by a massive elevation in [Ca(2+)](i), its active pool is severely depleted. In contrast, annexin A1 with a much lower Ca(2+) sensitivity is ineffective at the early stages of injury; however, it remains available for the repair even at high [Ca(2+)](i). Our findings highlight the role of the annexins in the process of plasmalemmal repair; a number of annexins with different Ca(2+)-sensitivities provide a cell with the means to react promptly to a limited injury in its early stages and, at the same time, to withstand a sustained injury accompanied by the continuous formation of plasmalemmal lesions.