Impaired Mitochondrial Energy Production Causes Light-Induced Photoreceptor Degeneration Independent of Oxidative Stress

Two insults often underlie a variety of eye diseases including glaucoma, optic atrophy, and retinal degeneration—defects in mitochondrial function and aberrant Rhodopsin trafficking. Although mitochondrial defects are often associated with oxidative stress, they have not been linked to Rhodopsin trafficking. In an unbiased forward genetic screen designed to isolate mutations that cause photoreceptor degeneration, we identified mutations in a nuclear-encoded mitochondrial gene, ppr, a homolog of human LRPPRC. We found that ppr is required for protection against light-induced degeneration. Its function is essential to maintain membrane depolarization of the photoreceptors upon repetitive light exposure, and an impaired phototransduction cascade in ppr mutants results in excessive Rhodopsin1 endocytosis. Moreover, loss of ppr results in a reduction in mitochondrial RNAs, reduced electron transport chain activity, and reduced ATP levels. Oxidative stress, however, is not induced. We propose that the reduced ATP level in ppr mutants underlies the phototransduction defect, leading to increased Rhodopsin1 endocytosis during light exposure, causing photoreceptor degeneration independent of oxidative stress. This hypothesis is bolstered by characterization of two other genes isolated in the screen, pyruvate dehydrogenase and citrate synthase. Their loss also causes a light-induced degeneration, excessive Rhodopsin1 endocytosis and reduced ATP without concurrent oxidative stress, unlike many other mutations in mitochondrial genes that are associated with elevated oxidative stress and light-independent photoreceptor demise.     

Pseudofossils in relict methane seep carbonates resemble endemic microbial consortia

Pleistocene-age methane seep carbonates from the Eel River Basin, California contain aggregate-like structures composed of tightly-packed hollow spheres that morphologically resemble syntrophic archaeal–bacterial consortia known to catalyze the anaerobic oxidation of methane (AOM). Tetragonal microstructures also present in the carbonates resemble seep-endemic Methanosarcinales cell clusters. Despite morphological similarities to the seep-endemic microbes that likely mediated the authigenesis of Eel River Basin carbonates and sulfides, detailed petrographic, SEM, and magnetic microscopic imaging, remanence rock magnetism, laser Raman, and energy dispersive X-ray spectroscopy, suggest that these microstructures are not microfossils, but rather mineral structures that result from the diagenetic alteration of euhedral Fe-sulfide framboids. Electron microscopy shows that during diagenesis, reaction rims composed of Fe oxide form around framboid microcrystalites. Subsequent dissolution of greigite or pyrite crystals leaves behind hollow cell-like casings (external molds) — a transformation that occurs on timescales of ～100 kyr or less. Despite their superficial resemblance to morphologically-distinctive extant microbes in local sediments, the presence of acellular precursor grains, as well as of partially-altered transitional forms, complicate the interpretation of these and other framboidal microstructures that have been reported from the rock record.     

Field Evaluation of Willow Under Short Rotation Coppice for Phytomanagement of Metal-Polluted Agricultural Soils

Short rotation coppice (SRC) of willow and poplar might be a promising phytoremediation option since it uses fast growing, high biomass producing tree species with often a sufficient metal uptake. This study evaluates growth, metal uptake and extraction potentials of eight willow clones (Belders, Belgisch Rood, Christina, Inger, Jorr, Loden, Tora and Zwarte Driebast) on a metal-contaminated agricultural soil, with total cadmium (Cd) and zinc (Zn) concentrations of 6.5 ± 0.8 and 377 ± 69 mg kg^?1 soil, respectively. Although, during the first cycle, on average generally low productivity levels (3.7 ton DM (dry matter) ha^?1 y^?1) were obtained on this sandy soil, certain clones exhibited quite acceptable productivity levels (e.g. Zwarte Driebast 12.5 ton DM ha^?1 y^?1). Even at low biomass productivity levels, SRC of willow showed promising removal potentials of 72 g Cd and 2.0 kg Zn ha^?1 y^?1, which is much higher than e.g. energy maize or rapeseed grown on the same soil. Cd and Zn removal can be increased by 40% if leaves are harvested as well. Nevertheless, nowadays the wood price remains the most critical factor in order to implement SRC as an acceptable, economically feasible alternative crop on metal-contaminated agricultural soils.     

Satb1 ablation alters temporal expression of immediate early genes and reduces dendritic spine density during postnatal brain development

Complex behaviors, such as learning and memory, are associated with rapid changes in gene expression of neurons and subsequent formation of new synaptic connections. However, how external signals are processed to drive specific changes in gene expression is largely unknown. We found that the genome organizer protein Satb1 is highly expressed in mature neurons, primarily in the cerebral cortex, dentate hilus, and amygdala. In Satb1-null mice, cortical layer morphology was normal. However, in postnatal Satb1-null cortical pyramidal neurons, we found a substantial decrease in the density of dendritic spines, which play critical roles in synaptic transmission and plasticity. Further, we found that in the cerebral cortex, Satb1 binds to genomic loci of multiple immediate early genes (IEGs) (Fos, Fosb, Egr1, Egr2, Arc, and Bdnf) and other key neuronal genes, many of which have been implicated in synaptic plasticity. Loss of Satb1 resulted in greatly alters timing and expression levels of these IEGs during early postnatal cerebral cortical development and also upon stimulation in cortical organotypic cultures. These data indicate that Satb1 is required for proper temporal dynamics of IEG expression. Based on these findings, we propose that Satb1 plays a critical role in cortical neurons to facilitate neuronal plasticity.     

Short rotation coppice culture of willows and poplars as energy crops on metal contaminated agricultural soils

Phytoremediation, more precisely phytoextraction, has been placed forward as an environmental friendly remediation technique, that can gradually reduce increased soil metal concentrations, in particular the bioavailable fractions. The aim of this study was to investigate the possibilities of growing willows and poplars under short rotation coppice (SRC) on an acid, poor, sandy metal contaminated soil, to combine in this way soil remediation by phytoextraction on one hand, and production of biomass for energy purposes on the other. Above ground biomass productivities were low for poplars to moderate for willows, which was not surprising, taking into account the soil conditions that are not very favorable for growth of these trees. Calculated phytoextraction efficiency was much longer for poplars than these for willows. We calculated that for phytoextraction in this particular case it would take at least 36 years to reach the legal threshold values for cadmium, but in combination with production of feedstock for bioenergy processes, this type of land use can offer an alternative income for local farmers. Based on the data of the first growing cycle, for this particular case, SRC of willows should be recommended.     

Using genetic variation to disentangle the complex relationship between food intake and health outcomes

Diet is considered as one of the most important modifiable factors influencing human health, but efforts to identify foods or dietary patterns associated with health outcomes often suffer from biases, confounding, and reverse causation. Applying Mendelian randomization in this context may provide evidence to strengthen causality in nutrition research. To this end, we first identified 283 genetic markers associated with dietary intake in 445,779 UK Biobank participants. We then converted these associations into direct genetic effects on food exposures by adjusting them for effects mediated via other traits. The SNPs which did not show evidence of mediation were then used for MR, assessing the association between genetically predicted food choices and other risk factors, health outcomes. We show that using all associated SNPs without omitting those which show evidence of mediation, leads to biases in downstream analyses (genetic correlations, causal inference), similar to those present in observational studies. However, MR analyses using SNPs which have only a direct effect on the exposure on food exposures provided unequivocal evidence of causal associations between specific eating patterns and obesity, blood lipid status, and several other risk factors and health outcomes.     

Seed dormancy and germination of the European Chaerophyllum temulum (Apiaceae), a member of a trans-Atlantic genus

BACKGROUND AND AIMS: The European Chaerophyllum temulum and two North American Chaerophyllum species have a trans-Atlantic disjunct distribution. This work aimed to resolve requirements for dormancy break and germination of C. temulum seeds and to compare dormancy traits with those of the two North American congeners. METHODS: Phenology of germination and embryo growth was studied by regularly exhuming seeds sown in natural conditions. Temperature requirements for embryo growth, breaking of dormancy and germination were determined by incubating seeds under controlled laboratory conditions. Additionally the effect of GA(3) on germination was tested to determine the specific dormancy type. KEY RESULTS: In natural conditions, embryo growth starts in early winter. Seedlings emerge in late winter shortly after the embryos reached the critical ratio for embryo length to seed length (E : S) of approx. 0.95. Growth of the embryo only occurs during a prolonged incubation period at 5 degrees C. After stratification at 5 degrees C, which breaks physiological and morphological dormancy, seeds can germinate at a wide range of temperatures. GA(3) did not substitute for cold stratification in seeds placed at 23 degrees C. CONCLUSIONS: Chaerophyllum temulum has deep complex morphophysiological dormancy. This dormancy type differs considerably from that of the two North American congeners.     

Biological activity of CXCL8 forms generated by alternative cleavage of the signal peptide or by aminopeptidase-mediated truncation

BackgroundPosttranslational modification of chemokines is one of the mechanisms that regulate leukocyte migration during inflammation. Multiple natural NH₂-terminally truncated forms of the major human neutrophil attractant interleukin-8 or CXCL8 have been identified. Although differential activity was reported for some CXCL8 forms, no biological data are available for others.ConclusionsIn terms of their ability to induce neutrophil recruitment in vivo, the multiple CXCL8 forms may be divided in three groups. The first group includes CXCL8 proteins consisting of 75 to 79 amino acids, cleaved by aminopeptidases, with intermediate activity on neutrophils. The second group, generated through proteolytic cleavage (e.g. by Ser proteases), contains 69 to 72 amino acid forms which are highly potent neutrophil attractants in vivo. A third category is generated through the modification of the arginine in the NH₂-terminal region into citrulline by peptidylarginine deiminases and has weak potency to induce neutrophil extravasation.     

A yeast-based model of alpha-synucleinopathy identifies compounds with therapeutic potential

We have developed a yeast-based model recapitulating neurotoxicity of alpha-synuclein fibrilization. This model recognized metal ions, known risk factors of alpha-synucleinopathy, as stimulators of alpha-synuclein aggregation and cytotoxicity. Elimination of Yca1 caspase activity augmented both cytotoxicity and inclusion body formation, suggesting the involvement of apoptotic pathway components in toxic alpha-synuclein amyloidogenesis. Deletion of hydrophobic amino acids at positions 66-74 in alpha-synuclein reduced its cytotoxicity but, remarkably, did not lower the levels of insoluble alpha-synuclein, indicating that noxious alpha-synuclein species are different from insoluble aggregates. A compound screen aimed at finding molecules with therapeutic potential identified flavonoids with strong activity to restrain alpha-synuclein toxicity. Subsequent structure-activity analysis elucidated that these acted by virtue of anti-oxidant and metal-chelating activities. In conclusion, this yeast-cell model as presented allows not only fundamental studies related to mechanisms of alpha-synuclein-instigated cellular degeneration, but is also a valid high-throughput identification tool for novel neuroprotective agents.