The Impact of Alpha-Syntrophin Deletion on the Changes in Tissue Structure and Extracellular Diffusion Associated with Cell Swelling under Physiological and Pathological Conditions

Aquaporin-4 (AQP4) is the primary cellular water channel in the brain and is abundantly expressed by astrocytes along the blood-brain barrier and brain-cerebrospinal fluid interfaces. Water transport via AQP4 contributes to the activity-dependent volume changes of the extracellular space (ECS), which affect extracellular solute concentrations and neuronal excitability. AQP4 is anchored by α-syntrophin (α-syn), the deletion of which leads to reduced AQP4 levels in perivascular and subpial membranes. We used the real-time iontophoretic method and/or diffusion-weighted magnetic resonance imaging to clarify the impact of α-syn deletion on astrocyte morphology and changes in extracellular diffusion associated with cell swelling in vitro and in vivo. In mice lacking α-syn, we found higher resting values of the apparent diffusion coefficient of water (ADC_W) and the extracellular volume fraction (α). No significant differences in tortuosity (λ) or non-specific uptake (k′), were found between α-syn-negative (α-syn −/−) and α-syn-positive (α-syn +/+) mice. The deletion of α-syn resulted in a significantly smaller relative decrease in α observed during elevated K⁺ (10 mM) and severe hypotonic stress (−100 mOsmol/l), but not during mild hypotonic stress (−50 mOsmol/l). After the induction of terminal ischemia/anoxia, the final values of ADC_W as well as of the ECS volume fraction α indicate milder cell swelling in α-syn −/− in comparison with α-syn +/+ mice. Shortly after terminal ischemia/anoxia induction, the onset of a steep rise in the extracellular potassium concentration and an increase in λ was faster in α-syn −/− mice, but the final values did not differ between α-syn −/− and α-syn +/+ mice. This study reveals that water transport through AQP4 channels enhances and accelerates astrocyte swelling. The substantially altered ECS diffusion parameters will likely affect the movement of neuroactive substances and/or trophic factors, which in turn may modulate the extent of tissue damage and/or drug distribution.     

Evidence of a landlocked reproducing population of the marine pejerrey Odontesthes argentinensis (Actinopterygii; Atherinopsidae)

In South America, the order Atheriniformes includes the monophyletic genus Odontesthes with 20 species that inhabit freshwater, estuarine and coastal environments. Pejerrey Odontesthes argentinensis is widely distributed in coastal and estuarine areas of the Atlantic Ocean and is known to foray into estuaries of river systems, particularly in conditions of elevated salinity. However, to our knowledge, a landlocked self-sustaining population has never been recorded. In this study, we examined the pejerrey population of Salada de Pedro Luro Lake (south-east of Buenos Aires Province, Argentina) to clarify its taxonomic identity. An integrative taxonomic analysis based on traditional meristic, landmark-based morphometrics and genetic techniques suggests that the Salada de Pedro Luro pejerrey population represents a novel case of physiological and morphological adaptation of a marine pejerrey species to a landlocked environment and emphasises the environmental plasticity of this group of fishes.     

Thermal habitat of adult Atlantic salmon Salmo salar in a warming ocean

The year-round thermal habitat at sea for adult Atlantic salmon Salmo salar (n = 49) from northern Norway was investigated using archival tags over a 10 year study period. During their ocean feeding migration, the fish spent 90% of the time in waters with temperatures from 1.6–8.4°C. Daily mean temperatures ranged from −0.5 to 12.9°C, with daily temperature variation up to 9.6°C. Fish experienced the coldest water during winter (November–March) and the greatest thermal range during the first summer at sea (July–August). Trends in sea-surface temperatures influenced the thermal habitat of salmon during late summer and autumn (August–October), with fish experiencing warmer temperatures in warmer years. This pattern was absent during winter (November–March), when daily mean temperatures ranged from 3.4–5.0°C, in both colder and warmer years. The observations of a constant thermal habitat during winter in both warmer and colder years, may suggest that the ocean distribution of salmon is flexible and that individual migration routes could shift as a response to spatiotemporal alterations of favourable prey fields and ocean temperatures.     

The crystal structure of Toxoplasma gondii nucleoside triphosphate diphosphohydrolase 1 represents a conformational intermediate in the reductive activation mechanism of the tetrameric enzyme

Toxoplasma gondii nucleoside triphosphate diphosphohydrolase (NTPDase) 1 was crystallized in an intermediate tetrameric conformation. The crystal structure is similar to that of T. gondii NTPDase3 and represents an inactive conformation as the activating disulfide bridge is not reduced and the active site cleft between the two domains of each monomer is open. However, the arrangement of the monomers within the tetramer differs from that of the inactive form of NTPDase3 and may represent an intermediate conformation on the path of the closure motion of the tetramer induced upon activation. Proteins 2013; 81:1271–1276. © 2013 Wiley Periodicals, Inc.     

Parkinson Disease Protein DJ-1 Binds Metals and Protects against Metal-induced Cytotoxicity

The progressive loss of motor control due to reduction of dopamine-producing neurons in the substantia nigra pars compacta and decreased striatal dopamine levels are the classically described features of Parkinson disease (PD). Neuronal damage also progresses to other regions of the brain, and additional non-motor dysfunctions are common. Accumulation of environmental toxins, such as pesticides and metals, are suggested risk factors for the development of typical late onset PD, although genetic factors seem to be substantial in early onset cases. Mutations of DJ-1 are known to cause a form of recessive early onset Parkinson disease, highlighting an important functional role for DJ-1 in early disease prevention. This study identifies human DJ-1 as a metal-binding protein able to evidently bind copper as well as toxic mercury ions in vitro. The study further characterizes the cytoprotective function of DJ-1 and PD-mutated variants of DJ-1 with respect to induced metal cytotoxicity. The results show that expression of DJ-1 enhances the cells'' protective mechanisms against induced metal toxicity and that this protection is lost for DJ-1 PD mutations A104T and D149A. The study also shows that oxidation site-mutated DJ-1 C106A retains its ability to protect cells. We also show that concomitant addition of dopamine exposure sensitizes cells to metal-induced cytotoxicity. We also confirm that redox-active dopamine adducts enhance metal-catalyzed oxidation of intracellular proteins in vivo by use of live cell imaging of redox-sensitive S3roGFP. The study indicates that even a small genetic alteration can sensitize cells to metal-induced cell death, a finding that may revive the interest in exogenous factors in the etiology of PD.     

Energetic Pathway Sampling in a Protein Interaction Domain

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The role of forest residues in the accounting for the global warming potential of bioenergy

Bioenergy makes up a significant portion of the global primary energy pie, and its production from modernized technology is foreseen to substantially increase. The climate neutrality of biogenic CO₂ emissions from bioenergy grown from sustainably managed biomass resource pools has recently been questioned. The temporary change caused in atmospheric CO₂ concentration from biogenic carbon fluxes was found to be largely dependent on the length of biomass rotation period. In this work, we also show the importance of accounting for the unutilized biomass that is left to decompose in the resource pool and how the characterization factor for the climate impact of biogenic CO₂ emissions changes whether residues are removed for bioenergy or not. With the case of Norwegian Spruce biomass grown in Norway, we found that significantly more biogenic CO₂ emissions should be accounted towards contributing to global warming potential when residues are left in the forest. For a 100‐year time horizon, the global warming potential bio factors suggest that between 44 and 62% of carbon‐flux, neutral biogenic CO₂ emissions at the energy conversion plant should be attributed to causing equivalent climate change potential as fossil‐based CO₂ emissions. For a given forest residue extraction scenario, the same factor should be applied to the combustion of any combination of stem and forest residues. Life cycle analysis practitioners should take these impacts into account and similar region/species specific factors should be developed.     

How the Polls Can Be Both Spot On and Dead Wrong: Using Choice Blindness to Shift Political Attitudes and Voter Intentions

Political candidates often believe they must focus their campaign efforts on a small number of swing voters open for ideological change. Based on the wisdom of opinion polls, this might seem like a good idea. But do most voters really hold their political attitudes so firmly that they are unreceptive to persuasion? We tested this premise during the most recent general election in Sweden, in which a left- and a right-wing coalition were locked in a close race. We asked our participants to state their voter intention, and presented them with a political survey of wedge issues between the two coalitions. Using a sleight-of-hand we then altered their replies to place them in the opposite political camp, and invited them to reason about their attitudes on the manipulated issues. Finally, we summarized their survey score, and asked for their voter intention again. The results showed that no more than 22% of the manipulated replies were detected, and that a full 92% of the participants accepted and endorsed our altered political survey score. Furthermore, the final voter intention question indicated that as many as 48% (±9.2%) were willing to consider a left-right coalition shift. This can be contrasted with the established polls tracking the Swedish election, which registered maximally 10% voters open for a swing. Our results indicate that political attitudes and partisan divisions can be far more flexible than what is assumed by the polls, and that people can reason about the factual issues of the campaign with considerable openness to change.     

Medical and Social Determinants of Subsequent Labour Market Marginalization in Young Hospitalized Suicide Attempters

Background

Individuals with a history of suicide attempt have a high risk for subsequent labour market marginalization. This study aimed at assessing the effect of individual and parental factors on different measures of marginalization.

Methods

Prospective cohort study based on register linkage of 5 649 individuals who in 1994 were 16–30 years old, lived in Sweden and were treated in inpatient care for suicide attempt during 1992–1994. Hazard ratios (HRs) for labour market marginalization defined as long-term unemployment (>180 days), sickness absence (>90 days), or disability pension in 1995–2010 were calculated with Cox regression.

Results

Medical risk factors, particularly any earlier diagnosed specific mental disorders (e.g., schizophrenia: HR 5.4 (95% CI: 4.2, 7.0), personality disorders: HR 3.9, 95% CI: 3.1, 4.9), repetitive suicide attempts (HR 1.6, 95% CI: 1.4, 1.9) were associated with a higher relative risk of disability pension. Individual medical factors were of smaller importance for long-term sickness absence, and of only marginal relevance to long-term unemployment. Country of birth outside Europe had an opposite effect on disability pension (HR 0.6, 95% CI: 0.4, 0.8) and long-term unemployment (HR 1.5, 95% CI: 1.3, 1.8). Female sex was positively correlated with long-term sickness absence (HR 1.6, 95% CI: 1.4, 1.7), and negatively associated with long-term unemployment (HR: 0.8, 95% CI: 0.7, 0.9).

Conclusions

As compared to disability pension, long-term sickness absence and unemployment was more strongly related to socio-economic variables. Marginalization pathways seemed to vary with migration status and sex. These findings may contribute to the development of intervention strategies which take the individual risk for marginalization into account.