Metabolic profiling of a transgenic Caenorhabditis elegans Alzheimer model

Despite decades of research, no early-onset biomarkers are currently available for Alzheimer’s disease, a cureless neurodegenerative disease afflicting millions worldwide. In this study, transgenic Caenorhabditis elegans were used to investigate changes in the metabolome after induced expression of amyloid-β. GC- and LC–MS-based platforms determined a total of 157 differential features. Some of these were identified using in-house (GC–MS) or public libraries (LC–MS), revealing changes in allantoin, cystathionine and tyrosine levels. Since C. elegans is far better suited to metabolomics studies than most other model systems, the accordance of these findings with vertebrate literature is promising and argues for further use of C. elegans as a model of human pathology in the study of AD

San Francisco Bay Area corporate history : a selected annotated bibliography

Human activities, among which dredging and land use change in river basins, are altering estuarine ecosystems. These activities may result in changes in sedimentary processes, affecting biodiversity of sediment macrofauna. As macrofauna controls sediment chemistry and fluxes of energy and matter between water column and sediment, changes in the structure of macrobenthic communities could affect the functioning of an entire ecosystem. We assessed the impact of sediment deposition on intertidal macrobenthic communities and on rates of an important ecosystem function, i.e. sediment community oxygen consumption (SCOC). An experiment was performed with undisturbed sediment samples from the Scheldt river estuary (SW Netherlands). The samples were subjected to four sedimentation regimes: one control and three with a deposited sediment layer of 1, 2 or 5 cm. Oxygen consumption was measured during incubation at ambient temperature. Luminophores applied at the surface, and a seawater–bromide mixture, served as tracers for bioturbation and bio-irrigation, respectively. After incubation, the macrofauna was extracted, identified, and counted and then classified into functional groups based on motility and sediment reworking capacity. Total macrofaunal densities dropped already under the thinnest deposits. The most affected fauna were surficial and low-motility animals, occurring at high densities in the control. Their mortality resulted in a drop in SCOC, which decreased steadily with increasing deposit thickness, while bio-irrigation and bioturbation activity showed increases in the lower sediment deposition regimes but decreases in the more extreme treatments. The initial increased activity likely counteracted the effects of the drop in low-motility, surficial fauna densities, resulting in a steady rather than sudden fall in oxygen consumption. We conclude that the functional identity in terms of motility and sediment reworking can be crucial in our understanding of the regulation of ecosystem functioning and the impact of habitat alterations such as sediment deposition

A multi-parent recombinant inbred line population of C. elegans allows identification of novel QTLs for complex life history traits

Background The nematode Caenorhabditis elegans has been extensively used to explore the relationships between complex traits, genotypes, and environments. Complex traits can vary across different genotypes of a species, and the genetic regulators of trait variation can be mapped on the genome using quantitative trait locus (QTL) analysis of recombinant inbred lines (RILs) derived from genetically and phenotypically divergent parents. Most RILs have been derived from crossing two parents from globally distant locations. However, the genetic diversity between local C. elegans populations can be as diverse as between global populations and could thus provide means of identifying genetic variation associated with complex traits relevant on a broader scale. Results To investigate the effect of local genetic variation on heritable traits, we developed a new RIL population derived from 4 parental wild isolates collected from 2 closely located sites in France: Orsay and Santeuil. We crossed these 4 genetically diverse parental isolates to generate a population of 200 multi-parental RILs and used RNA-seq to obtain sequence polymorphisms identifying almost 9000 SNPs variable between the 4 genotypes with an average spacing of 11 kb, doubling the mapping resolution relative to currently available RIL panels for many loci. The SNPs were used to construct a genetic map to facilitate QTL analysis. We measured life history traits such as lifespan, stress resistance, developmental speed, and population growth in different environments, and found substantial variation for most traits. We detected multiple QTLs for most traits, including novel QTLs not found in previous QTL analysis, including those for lifespan and pathogen responses. This shows that recombining genetic variation across C. elegans populations that are in geographical close proximity provides ample variation for QTL mapping. Conclusion Taken together, we show that using more parents than the classical two parental genotypes to construct a RIL population facilitates the detection of QTLs and that the use of wild isolates facilitates the detection of QTLs. The use of multi-parent RIL populations can further enhance our understanding of local adaptation and life history trade-offs

Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans

Severe mitochondria deficiency leads to a number of devastating degenerative disorders, yet, mild mitochondrial dysfunction in different species, including the nematode Caenorhabditis elegans, can have pro-longevity effects. This apparent paradox indicates that cellular adaptation to partial mitochondrial stress can induce beneficial responses, but how this is achieved is largely unknown. Complete absence of frataxin, the mitochondrial protein defective in patients with Friedreich's ataxia, is lethal in C. elegans, while its partial deficiency extends animal lifespan in a p53 dependent manner. In this paper we provide further insight into frataxin control of C. elegans longevity by showing that a substantial reduction of frataxin protein expression is required to extend lifespan, affect sensory neurons functionality, remodel lipid metabolism and trigger autophagy. We find that Beclin and p53 genes are required to induce autophagy and concurrently reduce lipid storages and extend animal lifespan in response to frataxin suppression. Reciprocally, frataxin expression modulates autophagy in the absence of p53. Human Friedreich ataxia-derived lymphoblasts also display increased autophagy, indicating an evolutionarily conserved response to reduced frataxin expression. In sum, we demonstrate a causal connection between induction of autophagy and lifespan extension following reduced frataxin expression, thus providing the rationale for investigating autophagy in the pathogenesis and treatment of Friedreich's ataxia and possibly other human mitochondria-associated disorders

Functional trait responses to sediment deposition reduce macrofauna-mediated ecosystem functioning in an estuarine mudflat

Human activities, among which dredging and land use change in river basins, are altering estuarine ecosystems. These activities may result in changes in sedimentary processes, affecting biodiversity of sediment macrofauna. As macrofauna controls sediment chemistry and fluxes of energy and matter between water column and sediment, changes in the structure of macrobenthic communities could affect the functioning of an entire ecosystem. We assessed the impact of sediment deposition on intertidal macrobenthic communities and on rates of an important ecosystem function, i.e. sediment community oxygen consumption (SCOC). An experiment was performed with undisturbed sediment samples from the Scheldt river estuary (SW Netherlands). The samples were subjected to four sedimentation regimes: one control and three with a deposited sediment layer of 1, 2 or 5 cm. Oxygen consumption was measured during incubation at ambient temperature. Luminophores applied at the surface, and a seawater–bromide mixture, served as tracers for bioturbation and bio-irrigation, respectively. After incubation, the macrofauna was extracted, identified, and counted and then classified into functional groups based on motility and sediment reworking capacity. Total macrofaunal densities dropped already under the thinnest deposits. The most affected fauna were surficial and low-motility animals, occurring at high densities in the control. Their mortality resulted in a drop in SCOC, which decreased steadily with increasing deposit thickness, while bio-irrigation and bioturbation activity showed increases in the lower sediment deposition regimes but decreases in the more extreme treatments. The initial increased activity likely counteracted the effects of the drop in low-motility, surficial fauna densities, resulting in a steady rather than sudden fall in oxygen consumption. We conclude that the functional identity in terms of motility and sediment reworking can be crucial in our understanding of the regulation of ecosystem functioning and the impact of habitat alterations such as sediment deposition

Organism-sediment interactions govern post-hypoxia recovery of ecosystem functioning

Hypoxia represents one of the major causes of biodiversity and ecosystem functioning loss for coastal waters. Since eutrophication-induced hypoxic events are becoming increasingly frequent and intense, understanding the response of ecosystems to hypoxia is of primary importance to understand and predict the stability of ecosystem functioning. Such ecological stability may greatly depend on the recovery patterns of communities and the return time of the system properties associated to these patterns. Here, we have examined how the reassembly of a benthic community contributed to the recovery of ecosystem functioning following experimentally-induced hypoxia in a tidal flat. We demonstrate that organism-sediment interactions that depend on organism size and relate to mobility traits and sediment reworking capacities are generally more important than recovering species richness to set the return time of the measured sediment processes and properties. Specifically, increasing macrofauna bioturbation potential during community reassembly significantly contributed to the recovery of sediment processes and properties such as denitrification, bedload sediment transport, primary production and deep pore water ammonium concentration. Such bioturbation potential was due to the replacement of the small-sized organisms that recolonised at early stages by large-sized bioturbating organisms, which had a disproportionately stronger influence on sediment. This study suggests that the complete recovery of organism-sediment interactions is a necessary condition for ecosystem functioning recovery, and that such process requires long periods after disturbance due to the slow growth of juveniles into adult stages involved in these interactions. Consequently, repeated episodes of disturbance at intervals smaller than the time needed for the system to fully recover organism-sediment interactions may greatly impair the resilience of ecosystem functioning.