7 research outputs found
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The INtegrated CAtchment model of phosphorus dynamics (INCA-P): description and demonstration of new model structure and equations
INCA-P is a dynamic, catchment-scale phosphorus model which has been widely applied during the last decade. Since its original release in 2002, the model structure and equations have been significantly altered during several development phases. Here, we provide the first full model description since 2002 and then test the latest version of the model (v1.4.4) in a small rural catchment in northeast Scotland. The particulate phosphorus simulation was much improved compared to previous model versions, whilst the latest sorption equations allowed us to explore the potential time lags between reductions in terrestrial inputs and improvements in surface water quality, an issue of key policy relevance. The model is particularly suitable for use as a research tool, but should only be used to inform policy and land management in data-rich areas, where parameters and processes can be well-constrained. More long-term data is needed to parameterise dynamic models and test their predictions
Surgical Criteria for Obstructive Sleep Apnea Syndrome Based on Localization of Upper Airway Collapse during Sleep: A Preliminary Study.
A Court Quietly Rewrote the Federal Pesticide Statute: How Prevalent is Judicial Statutory Revision?
HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder
Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an essential, ubiquitously abundant protein involved in mRNA processing. Genetic variants in other members of the HNRNP family have been associated with neurodevelopmental disorders. Here, we describe 13 individuals with global developmental delay, intellectual disability, behavioral abnormalities, and subtle facial dysmorphology with heterozygous HNRNPC germline variants. Five of them bear an identical in-frame deletion of nine amino acids in the extreme C terminus. To study the effect of this recurrent variant as well as HNRNPC haploinsufficiency, we used induced pluripotent stem cells (iPSCs) and fibroblasts obtained from affected individuals. While protein localization and oligomerization were unaffected by the recurrent C-terminal deletion variant, total HNRNPC levels were decreased. Previously, reduced HNRNPC levels have been associated with changes in alternative splicing. Therefore, we performed a meta-analysis on published RNA-seq datasets of three different cell lines to identify a ubiquitous HNRNPC-dependent signature of alternative spliced exons. The identified signature was not only confirmed in fibroblasts obtained from an affected individual but also showed a significant enrichment for genes associated with intellectual disability. Hence, we assessed the effect of decreased and increased levels of HNRNPC on neuronal arborization and neuronal migration and found that either condition affects neuronal function. Taken together, our data indicate that HNRNPC haploinsufficiency affects alternative splicing of multiple intellectual disability-associated genes and that the developing brain is sensitive to aberrant levels of HNRNPC. Hence, our data strongly support the inclusion of HNRNPC to the family of HNRNP-related neurodevelopmental disorders