17 research outputs found
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