An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients

Neurodegenerative diseases are challenging for systems biology because of the lack of reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could address these challenges. We investigated DNA, RNA, epigenetics, and proteins in iPSC-derived motor neurons from patients with ALS carrying hexanucleotide expansions in C9ORF72. Using integrative computational methods combining all omics datasets, we identified novel and known dysregulated pathways. We used a C9ORF72 Drosophila model to distinguish pathways contributing to disease phenotypes from compensatory ones and confirmed alterations in some pathways in postmortem spinal cord tissue of patients with ALS. A different differentiation protocol was used to derive a separate set of C9ORF72 and control motor neurons. Many individual -omics differed by protocol, but some core dysregulated pathways were consistent. This strategy of analyzing patient-specific neurons provides disease-related outcomes with small numbers of heterogeneous lines and reduces variation from single-omics to elucidate network-based signatures

Nutrient limitation of periphyton growth in arctic lakes in south-west Greenland

This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Many arctic lakes are oligotrophic systems where phototrophic growth is controlled by nutrient supply. Recent anthropogenic nutrient loading is associated with biological and/or physico-chemical change in several lakes across the arctic. Shifts in nutrient limitation (nitrogen (N), phosphorus (P), or N ? P) and associated effects on the growth and composition of algal communities are commonly reported. The Kangerlussuaq region of south-west Greenland forms a major lake district which is considered to receive little direct anthropogenic disturbance. However, long-range transport of pollutant N is now reaching Greenland, and it was hypothesised that a precipitation gradient from the inland ice sheet margin to the coast might also deliver increased N deposition. In situ nutrient bioassays were deployed in three lakes across the region: ice sheet margin, inland (close to Kangerlussuaq) and the coast (near Sisimiut), to determine nutrient limitation of lakes and investigate any effects of nutrients on periphyton growth and community composition. Nutrient limitation differed amongst lakes: N limitation (ice sheet margin), N and P limitation (inland) and N ? P co-limitation (coast). Factors including variation in N supply, ice phenology, seasonal algal succession, community structure and physical limnology are explored as mechanisms to explain differences amongst lakes. Nutrient limitation of arctic lakes and associated ecological impacts are highly variable, even across small geographic areas. In this highly sensitive region, future environmental change scenarios carry a strong risk of significantly altering nutrient limitation; in turn, potentially severely impacting lake structure and function