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.     

Fisheries Certification in Russia: The Emergence of Nonstate Authority in a Postcommunist Economy

Market-based incentives are a new approach to direct fisheries toward greater sustainability. The Marine Stewardship Council (MSC) is the leading certification scheme for wild capture fisheries. Four Russian fisheries were certified from 2010 to 2014. Despite a slow start, the Russian fishery assessments have gone more quickly, received less public criticism, and scored better over time. Consensus is emerging that the Russian system for fisheries management fulfills the MSC requirements.     

Three dimensional patient-specific collagen architecture modulates cartilage responses in the knee joint during gait

Site-specific variation of collagen fibril orientations can affect cartilage stresses in knee joints. However, this has not been confirmed by 3-D analyses. Therefore, we present a novel method for evaluation of the effect of patient-specific collagen architecture on time-dependent mechanical responses of knee joint cartilage during gait. 3-D finite element (FE) models of a human knee joint were created with the collagen architectures obtained from T₂ mapped MRI (patient-specific model) and from literature (literature model). The effect of accuracy of the implementation of collagen fibril architecture into the model was examined by using a submodel with denser FE mesh. Compared to the literature model, fibril strains and maximum principal stresses were reduced especially in the superficial/middle regions of medial tibial cartilage in the patient-specific model after the loading response of gait (up to ?413 and ?26%, respectively). Compared to the more coarsely meshed joint model, the patient-specific submodel demonstrated similar strain and stress distributions but increased values particularly in the superficial cartilage regions (especially stresses increased >60%). The results demonstrate that implementation of subject-specific collagen architecture of cartilage in 3-D modulates location- and time-dependent mechanical responses of human knee joint cartilage. Submodeling with more accurate implementation of collagen fibril architecture alters cartilage stresses particularly in the superficial/middle tissue.     

Strong Interplay between Sodium and Oxygen in Kesterite Absorbers: Complex Formation,Incorporation, and Tailoring Depth Distributions

Sodium and oxygen are prevalent impurities in kesterite solar cells. Both elements are known to strongly impact performance of the kesterite devices and can be connected to efficiency improvements seen after heat treatments. The sodium distribution in the kesterite absorber is commonly reported, whereas the oxygen distribution has received less attention. Here, a direct relationship between sodium and oxygen in kesterite absorbers is established using secondary ion mass spectrometry and explained by defect analyses within the density functional theory. The calculations reveal a binding energy of 0.76 eV between the substitutional defects Na_Cu and O_S in the nearest neighbor configuration, indicating an abundance of Na? O complexes in kesterite absorbers at relevant temperatures. Oxygen incorporation is studied by introducing isotopic ¹⁸O at different stages of the Cu₂ZnSnS₄/Mo/soda‐lime glass baseline processing. It is observed that oxygen from the Mo back contact and contaminations during the sulfurization are primary contributors to the oxygen distribution. Indeed, unintentional oxygen incorporation leads to immobilization of sodium. This results in a strong correlation between sodium and oxygen, in excellent agreement with the theoretical calculations. Consequently, oxygen availability should be monitored to optimize postdeposition heat treatments to control impurities in kesterite absorbers and ultimately, the solar cell efficiency.     

Modelling spatial dynamics of fish

Our ability to model spatial distributions of fish populations is reviewed by describing the available modelling tools. Ultimate models of the individual's motivation for behavioural decisions are derived from evolutionary ecology. Mechanistic models for how fish sense and may respond to their surroundings are presented for vision, olfaction, hearing, the lateral line and other sensory organs. Models for learning and memory are presented, based both upon evolutionary optimization premises and upon neurological information processing and decision making. Functional tools for modelling behaviour and life histories can be categorized as belonging to an optimization or an adaptation approach. Among optimization tools, optimal foraging theory, life history theory, ideal free distribution, game theory and stochastic dynamic programming are presented. Among adaptation tools, genetic algorithms and the combination with artificial neural networks are described. The review advocates the combination of evolutionary and neurological approaches to modelling spatial dynamics of fish.     

Stroke and glide of wing-propelled divers: deep diving seabirds adjust surge frequency to buoyancy change with depth

In order to increase locomotor efficiency, breath-holding divers are expected to adjust their forward thrusts in relation to changes of buoyancy with depth. Wing propulsion during deep diving by Brünnich's guillemots (Uria lomvia) was measured in the wild by high-speed (32 Hz) sampling of surge (tail-to-head) and heave (ventral-to-dorsal) accelerations with bird-borne data loggers. At the start of descent, the birds produced frequent surges (3.2 Hz) during both the upstroke and the downstroke against buoyancy to attain a mean speed of 1.2-1.8 m s(-1) that was close to the expected optimal swim speed. As they descended deeper, the birds decreased the frequency of surges to 2.4 Hz, relaying only on the downstroke. During their ascent, they stopped stroking at 18 m depth, after which the swim speed increased to 2.3 m s(-1), possibly because of increasing buoyancy as air volumes expanded. This smooth change of surge frequency was achieved while maintaining a constant stroke duration (0.4-0.5 s), presumably allowing efficient muscle contraction.     

Organization of ribosomal protein genes in Escherichia coli: II. Mapping of ribosomal protein genes by in vitro synthesis of ribosomal proteins using DNA fragments of a transducing phage as templates

The structural genes for six ribosomal proteins (r-proteins) located in the str-spc region around 64 minutes on the Escherichia coli chromosome have been mapped physically with respect to each other and the neighboring genes aroE and trkA. The genes code for the 30 S r-proteins S4 (ram), S5 (spc), S8, S11, S13 and S14. Furthermore, regions coding for unidentified 50 S r-proteins have been indicated.The mapping was performed by biochemical methods employing DNA from the specialized transducing phage λspc1, which carries the aroE-trkA-spc region of the E. coli chromosome. The phage DNA was cleaved by restriction endonucleases, and the generated DNA fragments used as templates for synthesis of r-proteins in a DNA-dependent cell-free system. Since the relative order of the DNA fragments created by the restriction endonucleases is known, a genetic map could be constructed.     

Indigenous Bacteria in Hemolymph and Tissues of Marine Bivalves at Low Temperatures

Hemolymph and soft tissues of Pacific oysters (Crassostrea gigas) kept in sand-filtered seawater at temperatures between 1 and 8°C were normally found to contain bacteria, with viable counts (CFU) in hemolymph in the range 1.4 × 10² to 5.6 × 10² bacteria per ml. Pseudomonas, Alteromonas, Vibrio, and Aeromonas organisms dominated, with a smaller variety of morphologically different unidentified strains. Hemolymph and soft tissues of horse mussels (Modiolus modiolus), locally collected from a 6- to 10-m depth in the sea at temperatures between 4 and 6°C, also contained bacteria. The CFU in horse mussel hemolymph was of the same magnitude as that in oysters (mean, 2.6 × 10⁴), and the bacterial flora was dominated by Pseudomonas (61.3%), Vibrio (27.0%), and Aeromonas (11.7%) organisms. In soft tissues of horse mussels, a mean CFU of 2.9 × 10⁴ bacteria per g was found, with Vibrio (38.5%), Pseudomonas (33.0%), and Aeromonas (28.5%) constituting the major genera. After the challenge of oysters in seawater at 4°C to the psychrotrophic fish pathogen Vibrio salmonicida (strains NCIMB 2245 from Scotland and TEO 84001 from Norway) and a commensal Aeromonas sp. isolated from oysters, the viable count in hemolymph increased 1,000-fold to about 10⁵ bacteria per ml. In soft tissues, about a 1,000-fold increase in CFU to 6 × 10⁷ was observed. V. salmonicida NCIMB 2245 invaded hemolymph and soft tissues after 14 days and dominated these compartments after 41 days, whereas strain TEO 84001 did not invade soft tissues to the same extent. Challenge with V. salmonicida NCIMB 2245 resulted in 100% mortality, whereas about 50% of the oysters survived challenge with the Norwegian strain, TEO 84001. The commensal Aeromonas sp. invaded hemolymph and soft tissues and caused 100% mortality. Oyster hemolymph contained agglutinins for Vibrio anguillarum but not for V. salmonicida, whereas we did not find agglutinins for either of these bacteria in horse mussels. Agglutinins for horse and human erythrocytes were found in hemolymph from both animals. We found no differences in agglutinin titers in oysters from different Norwegian locations, and long-term challenge with bacteria in seawater did not result in changes of agglutinin activity. These studies demonstrate that bacteria exist in hemolymph and soft tissues of marine bivalves at temperatures below 8°C. Increased bacterial numbers in seawater at 4°C result in augmented invasion of bacteria in hemolymph and soft tissues. V. salmonicida, a bacterium pathogenic for fish at low temperatures, invades bivalve hemolymph and soft tissues, and thus bivalves may serve as a reservoir for pathogens of fish at low seawater temperatures.     

Association of TERC and OBFC1 Haplotypes with Mean Leukocyte Telomere Length and Risk for Coronary Heart Disease

Objective

To replicate the associations of leukocyte telomere length (LTL) with variants at four loci and to investigate their associations with coronary heart disease (CHD) and type II diabetes (T2D), in order to examine possible causal effects of telomere maintenance machinery on disease aetiology.

Methods

Four SNPs at three loci BICD1 (rs2630578 GγC), 18q12.2 (rs2162440 GγT), and OBFC1 (rs10786775 CγG, rs11591710 AγC) were genotyped in four studies comprised of 2353 subjects out of which 1148 had CHD and 566 T2D. Three SNPs (rs12696304 CγG, rs10936601G>T and rs16847897 GγC) at the TERC locus were genotyped in these four studies, in addition to an offspring study of 765 healthy students. For all samples, LTL had been measured using a real-time PCR-based method.

Results

Only one SNP was associated with a significant effect on LTL, with the minor allele G of OBFC1 rs10786775 SNP being associated with longer LTL (β=0.029, P=0.04). No SNPs were significantly associated with CHD or T2D. For OBFC1 the haplotype carrying both rare alleles (rs10786775G and rs11591710C, haplotype frequency 0.089) was associated with lower CHD prevalence (OR: 0.77; 95% CI: 0.61–0.97; P= 0.03). The TERC haplotype GTC (rs12696304G, rs10936601T and rs16847897C, haplotype frequency 0.210) was associated with lower risk for both CHD (OR: 0.86; 95% CI: 0.75-0.99; P=0.04) and T2D (OR: 0.74; 95% CI: 0.61–0.91; P= 0.004), with no effect on LTL. Only the last association remained after adjusting for multiple testing.

Conclusion

Of reported associations, only that between the OBFC1 rs10786775 SNP and LTL was confirmed, although our study has a limited power to detect modest effects. A 2-SNP OBFC1 haplotype was associated with higher risk of CHD, and a 3-SNP TERC haplotype was associated with both higher risk of CHD and T2D. Further work is required to confirm these results and explore the mechanisms of these effects.