IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes.

GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach

One size does not fit all: Toward regional conservation practice guidance to reduce phosphorus loss risk in the Lake Erie watershed

Agricultural phosphorus (P) losses to surface water bodies remain a global eutrophication concern, despite the application of conservation practices on farm fields. Although it is generally agreed upon that the use of multiple conservation practices (“stacking”) will lead to greater improvements to water quality, this may not be cost effective to farmers, reducing the likelihood of adoption. At present, wholesale recommendations of conservation practices are given; however, the application of specific conservation practices in certain environments (e.g., no-till with surface application, cover crops) may not be effective and can even lead to unintended consequences. In this paper, we present the Lake Erie watershed as a case study. The Lake Erie watershed contains regions with unique physical geographies that include differences in climate, soil, topography, and land use, which have implications for both P transport from agricultural fields and the efficacy of conservation practices in mitigating P losses. We define major regions within the Lake Erie watershed where common strategies for conservation practice implementation are appropriate, and we propose a five-step plan for bringing regionally tailored, adaptive, and cost-conscious conservation practice into watershed planning. Although this paper is specific to the Lake Erie watershed, our framework can be transferred across broader geographic regions to provide guidance for watershed planning

Calcium action potentials in hair cells pattern auditory neuron activity before hearing onset

We found rat central auditory neurons to fire action potentials in a precise sequence of mini-bursts before the age of hearing onset. This stereotyped pattern was initiated by hair cells in the cochlea, which trigger brief bursts of action potentials in auditory neurons each time they fire a Ca2+spike. By generating theta-like activity, hair cells may limit the influence of synaptic depression in developing auditory circuits and promote consolidation of synapses