DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation

Parkinson's disease (PD) pathology is characterized by the degeneration of midbrain dopamine neurons (DNs) ultimately leading to a progressive movement disorder in patients. The etiology of DN loss in sporadic PD is unknown, although it is hypothesized that aberrant protein aggregation and cellular oxidative stress may promote DN degeneration. Homozygous mutations in DJ-1 were recently described in two families with autosomal recessive inherited PD (Bonifati et al. 2003). In a companion article (Martinat et al. 2004), we show that mutations in DJ-1 alter the cellular response to oxidative stress and proteasomal inhibition. Here we show that DJ-1 functions as a redox-sensitive molecular chaperone that is activated in an oxidative cytoplasmic environment. We further demonstrate that DJ-1 chaperone activity in vivo extends to alpha-synuclein, a protein implicated in PD pathogenesis.     

Dynamics of Ubiquitin Pools in Developing Sea Urchin Embryos

The sea urchin embryo is a closed metabolic system in which embryogenesis is accompanied by significant protein degradation. We report results which are consistent with a function for the ubiquitinmediated proteolytic pathway in selective protein degradation during embryogenesis in this system. Quantitative solid- and solution-phase immunochemical assays, employing anti-ubiquitin antibodies, showed that unfertilized eggs of Strongylocentrotus purpuratus have a high content of unconjugated ubiquitin ( ca . 8 × 10⁸ molecules), and also contain abundant conjugates involving ubiquitin and maternal proteins. The absolute content of ubiquitin in the conjugated form increases about 13-fold between fertilization and the pluteus larva stage; 90% or more of embryonic ubiquitin molecules are conjugated to embryonic proteins in hatched blastulae and later-stage embryos. Qualitatively similar results were obtained with embryos of Lytechinus variegatus . The results of pulse-labeling and immunoprecipitation experiments indicate that synthesis of ubiquitin in S. purpuratus is developmentally regulated, with an overall increase in synthetic rate of 12-fold between fertilization and hatching. Regulation is likely to occur at the level of translation, since others have shown that levels of ubiquitin-encoding mRNA remain virtually constant in echinoid embryos during this developmental interval. The sea urchin embryo should be a useful system for characterizing the role of ubiquitination in embryogenesis.     

The Genomic Basis of Color Pattern Polymorphism in the Harlequin Ladybird

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Histone H2A‐H2B binding by Pol α in the eukaryotic replisome contributes to the maintenance of repressive chromatin

The eukaryotic replisome disassembles parental chromatin at DNA replication forks, but then plays a poorly understood role in the re‐deposition of the displaced histone complexes onto nascent DNA. Here, we show that yeast DNA polymerase α contains a histone‐binding motif that is conserved in human Pol α and is specific for histones H2A and H2B. Mutation of this motif in budding yeast cells does not affect DNA synthesis, but instead abrogates gene silencing at telomeres and mating‐type loci. Similar phenotypes are produced not only by mutations that displace Pol α from the replisome, but also by mutation of the previously identified histone‐binding motif in the CMG helicase subunit Mcm2, the human orthologue of which was shown to bind to histones H3 and H4. We show that chromatin‐derived histone complexes can be bound simultaneously by Mcm2, Pol α and the histone chaperone FACT that is also a replisome component. These findings indicate that replisome assembly unites multiple histone‐binding activities, which jointly process parental histones to help preserve silent chromatin during the process of chromosome duplication.     

Comparison of solutes, nutrients, and bacteria inputs from two types of groundwater to the Rhône river during an artificial drought

Solute, nutrient and bacterial inputs to the River Rhône from the interstitial habitat of a gravel bar and the floodplain aquifer were investigated during an artificial drought. Eight springs were investigated: four groundwater-fed springs in the floodplain, located at the bottom of the bank; and four interstitial-fed springs located at the downstream end of a gravel bar. During this period, the inflows of groundwater to the river represented an average input of 0.77 mg l^–1 of nitrogen (of which 93.3% were nitrates), 0.0187 mg l^–1 of total phosphorus (of which 42.2% was orthophosphate), 3.56 mg l^–1 of silica, 2.315 ± 0.703 mg l^–1 of dissolved organic carbon (DOC, of which 47% was biodegradable) and 7.3 × 10⁴ ± 3.7 × 10⁴ bacteria per ml (of which 8.8% were active). Silica, DOC, biodegradable DOC, and bacteria concentrations displayed temporal variations during the study, which seem to be linked to the biological activity of the groundwater biofilm. There was a strong heterogeneity between the two types of groundwater that flow to the river: concentrations of calcium and alkalinity were higher in bank springs than in gravel bars springs. In these latters, sulfate, sodium, nitrogen, phosphorus were significantly higher.     

Are all GMOs the same? Consumer acceptance of cisgenic rice in India

India has more than 215 million food‐insecure people, many of whom are farmers. Genetically modified (GM) crops have the potential to alleviate this problem by increasing food supplies and strengthening farmer livelihoods. For this to occur, two factors are critical: (i) a change in the regulatory status of GM crops, and (ii) consumer acceptance of GM foods. There are generally two classifications of GM crops based on how they are bred: cisgenically bred, containing only DNA sequences from sexually compatible organisms; and transgenically bred, including DNA sequences from sexually incompatible organisms. Consumers may view cisgenic foods as more natural than those produced via transgenesis, thus influencing consumer acceptance. This premise was the catalyst for our study—would Indian consumers accept cisgenically bred rice and if so, how would they value cisgenics compared to conventionally bred rice, GM‐labelled rice and ‘no fungicide’ rice? In this willingness‐to‐pay study, respondents did not view cisgenic and GM rice differently. However, participants were willing‐to‐pay a premium for any aforementioned rice with a ‘no fungicide’ attribute, which cisgenics and GM could provide. Although not significantly different (P = 0.16), 76% and 73% of respondents stated a willingness‐to‐consume GM and cisgenic foods, respectively.     

High-Resolution Denitrification Kinetics in Pasture Soils Link N2O Emissions to pH,and Denitrification to C Mineralization

Denitrification in pasture soils is mediated by microbial and physicochemical processes leading to nitrogen loss through the emission of N₂O and N₂. It is known that N₂O reduction to N₂ is impaired by low soil pH yet controversy remains as inconsistent use of soil pH measurement methods by researchers, and differences in analytical methods between studies, undermine direct comparison of results. In addition, the link between denitrification and N₂O emissions in response to carbon (C) mineralization and pH in different pasture soils is still not well described. We hypothesized that potential denitrification rate and aerobic respiration rate would be positively associated with soils. This relationship was predicted to be more robust when a high resolution analysis is performed as opposed to a single time point comparison. We tested this by characterizing 13 different temperate pasture soils from northern and southern hemispheres sites (Ireland and New Zealand) using a fully automated-high-resolution GC detection system that allowed us to detect a wide range of gas emissions simultaneously. We also compared the impact of using different extractants for determining pH on our conclusions. In all pH measurements, soil pH was strongly and negatively associated with both N₂O production index (IN₂O) and N₂O/(N₂O+N₂) product ratio. Furthermore, emission kinetics across all soils revealed that the denitrification rates under anoxic conditions (NO+N₂O+N₂ μmol N/h/vial) were significantly associated with C mineralization (CO₂ μmol/h/vial) measured both under oxic (r² = 0.62, p = 0.0015) and anoxic (r² = 0.89, p<0.0001) conditions.     

The human VAV proto-oncogene maps to chromosome region 19p12→19p13.2

Summary A novel human oncogene, designated VAV, has been recently characterized. This oncogene was generated by a rearrangement within the 5 coding sequences of a normal cellular gene, the VAV proto-oncogene. The normal VAV gene is specifically expressed in hematopoietic cells regardless of their differentiation lineage. We now report that the VAV locus has been localized in the human genome at chromosome 19p12 19p13.2 by analysis of its segregation pattern in rodenthuman somatic cell hybrids and by chromosomal in situ hybridization. The VAV locus might be closely linked to the insulin receptor (INSR) locus, as suggested by comigration of INSR and VAV high-molecular-weight DNA fragments after pulsed-field gel electrophoresis. The VAV chromosomal assignment is of interest because chromosome region 19p13 is involved in different karyotypic abnormalities in a variety of malignancies including melanomas and leukemias. The identification of a novel proto-oncogene that maps to that region will enable us to define whether VAV is involved in any of the translocations observed.