Bacillithiol,a new role in buffering intracellular zinc

Zinc is a catalytic or structural cofactor of numerous proteins but can also be toxic if cells accumulate too much of this essential metal. Therefore, mechanisms of zinc homeostasis are needed to maintain a low but adequate amount of free zinc so that newly translated zinc‐dependent proteins can bind their cofactor without confounding issues of toxicity. These mechanisms include the regulation of uptake and efflux transporters and buffering of the free metal concentration by low‐molecular‐weight ligands in the cytosol. While many of the transporters involved in zinc homeostasis have been discovered in recent years, the molecules that buffer zinc have remained largely a mystery. In the new report highlighted by this commentary, Ma et al. (2014) provide convincing evidence that bacillithiol, the major low‐molecular‐weight thiol compound in Bacillus subtilis, serves as an important zinc buffer in those cells. Their discovery provides an important piece to the puzzle of how zinc buffering occurs in a large number of microbes and provides new clues about the role and relative importance of zinc buffering in all organisms.     

Liposomes for (trans)dermal drug delivery: the skin-PVPA as a novel in vitro stratum corneum model in formulation development

Penetration potential of vesicles destined for trans(dermal) administration remains to be of great interests both in respect to drug therapy and cosmetic treatment. This study investigated the applicability of the phospholipid vesicle-based permeation assay (PVPA) as a novel in vitro skin barrier model for screening purposes in preformulation studies. Various classes of liposomes containing hydrophilic model drug were examined, including conventional liposomes (CLs), deformable liposomes (DLs) and propylene glycol liposomes (PGLs). The size, surface charge, membrane deformability and entrapment efficiency were found to be affected by the vesicle lipid concentration, the presence of the surfactant and propylene glycol. All liposomes exhibited prolonged drug release profiles with an initial burst effect followed by a slower release phase. The permeation of the drug from all of the tested liposomes, as assessed with the mimicked stratum corneum – PVPA model, was significantly enhanced as compared to the permeability of the drug in solution form. Although the DLs and the PGLs exhibited almost the same membrane elasticity, the permeability of the drug delivered by PGLs was higher (6.2?×?10^?6?cm/s) than DLs (5.5?×?10^?6?cm/s). Therefore, this study confirmed both the potential of liposomes as vesicles in trans(dermal) delivery and potential of the newly developed skin-PVPA for the screening and optimization of liposomes at the early preformulation stage.     

Effects of functional feeds on the lipid composition,transcriptomic responses and pathology in heart of Atlantic salmon (Salmo salar L.) before and after experimental challenge with Piscine Myocarditis Virus (PMCV)

Background

Cardiomyopathy syndrome (CMS) is a severe cardiac disease of Atlantic salmon (Salmo salar) recently associated with a double-stranded RNA virus, Piscine Myocarditis Virus (PMCV). The disease has been diagnosed in 75-85 farms in Norway each year over the last decade resulting in annual economic losses estimated at up to €9 million. Recently, we demonstrated that functional feeds led to a milder inflammatory response and reduced severity of heart lesions in salmon experimentally infected with Atlantic salmon reovirus, the causal agent of heart and skeletal muscle inflammation (HSMI). In the present study we employed a similar strategy to investigate the effects of functional feeds, with reduced lipid content and increased eicosapentaenoic acid levels, in controlling CMS in salmon after experimental infection with PMCV.

Results

Hepatic steatosis associated with CMS was significantly reduced over the time course of the infection in fish fed the functional feeds. Significant differences in immune and inflammatory responses and pathology in heart tissue were found in fish fed the different dietary treatments over the course of the infection. Specifically, fish fed the functional feeds showed a milder and delayed inflammatory response and, consequently, less severity of heart lesions at earlier and later stages after infection with PMCV. Decreasing levels of phosphatidylinositol in cell membranes combined with the increased expression of genes related with T-cell signalling pathways revealed new interactions between dietary lipid composition and the immune response in fish during viral infection. Dietary histidine supplementation did not significantly affect immune responses or levels of heart lesions.

Conclusions

Combined with the previous findings on HSMI, the results of the present study highlight the potential role of clinical nutrition in controlling inflammatory diseases in Atlantic salmon. In particular, dietary lipid content and fatty acid composition may have important immune-modulatory effects in Atlantic salmon that could be potentially beneficial in fish balancing the immune and tissue responses to viral infections.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-462) contains supplementary material, which is available to authorized users.     

Early supported discharge after stroke in Bergen (ESD Stroke Bergen): three and six months results of a randomised controlled trial comparing two early supported discharge schemes with treatment as usual

Background

Stroke causes lasting disability and the burden of stroke is expected to increase substantially during the next decades. Optimal rehabilitation is therefore mandatory. Early supported discharge (ESD) has previously shown beneficial, but all major studies were carried out more than ten years ago. We wanted to implement and study the results of ESD in our community today with comparisons between ESD and treatment as usual, as well as between two different ESD models.

Methods

Patients with acute stroke were included during a three year period (2008–11) in a randomised controlled study comparing two different ESD models to treatment as usual. The two ESD models differed by the location of treatment: either in a day unit or in the patients’ homes. Patients in the ESD groups were followed by a multi-disciplinary ambulatory team in the stroke unit and discharged home as early as possible. The ESD models also comprised treatment by a multi-disciplinary community health team for up to five weeks and follow-up controls after 3 and 6 months. Primary outcome was modified Rankin Scale (mRS) at six months.

Results

Three-hundred-and-six patients were included. mRS scores and change scores were non-significantly better in the two ESD groups at 3 and 6 months. Within-group improvement from baseline to 3 months was significant in the ESD 1 (p?=?0.042) and ESD 2 (p?=?0.001) groups, but not in the controls. More patients in the pooled ESD groups were independent at 3 (p?=?0.086) and 6 months (p?=?0.122) compared to controls and there also was a significant difference in 3 month change score between them (p?=?0.049). There were no differences between the two ESD groups. Length of stay in the stroke unit was 11 days in all groups.

Conclusions

Patients in the ESD groups tended to be more independent than controls at 3 and 6 months, but no clear statistically significant differences were found. The added effect of supported discharge and improved follow-up seems to be rather modest. The improved stroke treatment of today may necessitate larger patient samples to demonstrate additional benefit of ESD.

Clinical trial registration

Unique identifier: NCT00771771

     

Farmed arctic foxes on the Fennoscandian mountain tundra: implications for conservation

Hybridization between wild and captive-bred individuals is a serious conservation issue that requires measures to prevent negative effects. Such measures are, however, often considered controversial by the public, especially when concerning charismatic species. One of the threats to the critically endangered Fennoscandian arctic fox Alopex lagopus is hybridization with escaped farm foxes, conveying a risk of outbreeding depression through loss of local adaptations to the lemming cycle. In this study, we investigate the existence of escaped farm foxes among wild arctic foxes and whether hybridization has occurred in the wild. We analysed mitochondrial control region sequences and 10 microsatellite loci in samples from free-ranging foxes and compared them with reference samples of known farm foxes and true Fennoscandian arctic foxes. We identified the farm fox specific mitochondrial haplotype H9 in 25 out of 182 samples, 21 of which had been collected within or nearby the wild subpopulation on Hardangervidda in south-western Norway. Genetic analyses of museum specimens collected on Hardangervidda (1897–1975) suggested that farm fox genotypes have recently been introduced to the area. Principal component analysis as well as both model- and frequency-based analyses of microsatellite data imply that the free-ranging H9s were farm foxes rather than wild arctic foxes and that the entire Hardangervidda population consisted of farm foxes or putative hybrids. We strongly recommend removal of farm foxes and hybrids in the wild to prevent genetic pollution of the remaining wild subpopulations of threatened arctic foxes.     

Costs of reproduction in circumpolar <Emphasis Type="Italic">Parnassia palustris</Emphasis> L. in light of global warming

In frequently burnt savannas, saplings face the formidable challenge of both recovering from, and eventually growing tall enough to escape from, frequent fire damage. The aim of this study was to explore how saplings allocate carbon to achieve these ends through carbon partitioning, storage and remobilization. Lignotuber total non-structural carbohydrate (TNC) concentrations and δ¹³C values of Acacia karroo (Fabaceae; Mimosoideae) were determined in plants from two different juvenile stages. These were one year after a fire when the plant consisted of numerous leafy shoots or coppices (“coppicing” stage), and three years after a fire when the plant consisted of one pole-like stem (“Gulliver” stage). Gulliver lignotubers were found to have significantly larger TNC pools (150 g vs. 97 g) and larger TNC concentrations (33% vs. 24%, w/w) than coppice lignotubers showing that post-coppice Gullivers recharged TNC in the lignotuber. δ¹³C values from the stems of plants in the Gulliver stage were significantly enriched (>1‰) in ¹³C compared to both coppicing (P < 0.01) and adult (P < 0.05) plants. Changes in both the amount of stored carbon and in the δ¹³C values indicated dependence on stored carbon reserves, and partially heterotrophic growth for initial resprouting. The plants appeared to use both current photosynthate and stored carbon reserves for growth of the Gulliver stem. The use of stored carbon is hypothesized to promote fast stem growth rates to a height where saplings escape fire injury.     

Simple models for extracting mechanical work from the ATP hydrolysis cycle

According to the binding-zipper model, the RecA class of ATPase motors converts chemical energy into mechanical force by the progressive annealing of hydrogen bonds between the nucleotide and the catalytic pocket. The role of hydrolysis is to weaken the binding of products, allowing them to be released so that the cycle can repeat. Molecular dynamics can be used to study the unbinding process, but the binding process is more complex, so that inferences about it are made indirectly from structural, mutation, and biochemical studies. Here we present a series of models of varying complexity that illustrate the basic processes involved in force production during ATP binding. These models reveal the role of solvent and geometry in determining the amount of mechanical work that can be extracted from the binding process.     

Holocene forest development along the Setesdal valley, southern Norway, reconstructed from macrofossil and pollen evidence

The Setesdal valley in South Norway runs north to south for 200 km, from alpine vegetation at 1200 m, passing the tree-line at around 1000 m, through Boreal forests, to Nemoral forest at sea level. The Holocene vegetation history and its altitudinal differentiation were reconstructed using pollen percentages and influx and plant macrofossil concentration records from four lakes along an altitudinal transect. During the early Holocene (c. 10500–8000 cal b.p.) Betula pubescens, Pinus sylvestris, Alnus, and Corylus expanded in the lowlands. Only Pinus and B. pubescens reached 1000 m asl (Lille Kjelavatn). Only B. pubescens reached Holebudalen (1144 m asl) at about the same time as it arrived in the lowlands. Between c. 8000–3000 cal b.p. mixed deciduous forest developed around Dalane (40 m asl) and to a lesser extent around Grostjørna (180 m asl), birch woodland with pine surrounded Lille Kjelavatn and birch woodland occurred at Holebudalen. From c. 3000 cal b.p. to present, the vegetation at Dalane hardly changed except for slight human impact and the immigration of Picea abies. At Grostjørna Pinus expanded. At Lille Kjelavatn Pinus disappeared and Betula became sparse as at the tree-line today. Betula retreated from Holebudalen thus leaving it above the tree-line in low-alpine vegetation. The strengths and weaknesses of pollen and plant macrofossil data were assessed for forest reconstructions. Where local pollen production is low, as near the tree-line, percentages of long-distance tree pollen can be misleadingly high. Pollen influxes of Betula and Pinus were much smaller near their altitudinal limits than at lower altitudes, although their macrofossils were equally abundant. The limited dispersal capacity of macrofossils documents the local presence of species and the character of the local vegetation, although macrofossils of some tree taxa are rarely found. Pollen and plant macrofossil evidence complement each other to provide a more complete reconstruction of Holocene tree-limits and tree-lines and hence climate changes, than either form of evidence alone.