Autism spectrum disorder (ASD) is a phenotypically and genetically heterogeneous neurodevelopmental disorder. Despite this heterogeneity, previous studies have shown patterns of molecular convergence in post-mortem brain tissue from autistic subjects. Here, we integrate genome-wide measures of mRNA expression, miRNA expression, DNA methylation, and histone acetylation from ASD and control brains to identify a convergent molecular subtype of ASD with shared dysregulation across both the epigenome and transcriptome. Focusing on this convergent subtype, we substantially expand the repertoire of differentially expressed genes in ASD and identify a component of upregulated immune processes that are associated with hypomethylation. We utilize eQTL and chromosome conformation datasets to link differentially acetylated regions with their cognate genes and identify an enrichment of ASD genetic risk variants in hyperacetylated noncoding regulatory regions linked to neuronal genes. These findings help elucidate how diverse genetic risk factors converge onto specific molecular processes in ASD.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease defined by motor neuron (MN) loss. Multiple genetic risk factors have been identified, implicating RNA and protein metabolism and intracellular transport, among other biological mechanisms. To achieve a systems-level understanding of the mechanisms governing ALS pathophysiology, we built gene co-expression networks using RNA-sequencing data from control human spinal cord samples, identifying 13 gene co-expression modules, each of which represents a distinct biological process or cell type. Analysis of four RNA-seq datasets from a range of ALS disease-associated contexts reveal dysregulation in numerous modules related to ribosomal function, wound response, and leukocyte activation, implicating astrocytes, oligodendrocytes, endothelia, and microglia in ALS pathophysiology. To identify potentially causal processes, we partitioned heritability across the genome, finding that ALS common genetic risk is enriched within two specific modules, SC.M4, representing genes related to RNA processing and gene regulation, and SC.M2, representing genes related to intracellular transport and autophagy and enriched in oligodendrocyte markers. Top hub genes of this latter module include ALS-implicated risk genes such as KPNA3, TMED2, and NCOA4, the latter of which regulates ferritin autophagy, implicating this process in ALS pathophysiology. These unbiased, genome-wide analyses confirm the utility of a systems approach to understanding the causes and drivers of ALS.

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Sulfur poisoning from engine fuel and lube is one of the most recognizable degradation mechanisms of a NO x adsorber catalyst system for diesel emission reduction. Even with the availability of 15 ppm sulfur diesel fuel, NO x adsorber will be deactivated without an effective sulfur management. Two general pathways are currently being explored for sulfur management: (1) the use of a disposable SO x trap that can be replaced or rejuvenated offline periodically, and (2) the use of diesel fuel injection in the exhaust and high temperature de-sulfation approach to remove the sulfur poisons to recover the NO x trapping efficiency. The major concern of the de-sulfation process is the many prolonged high temperature rich cycles that catalyst will encounter during its useful life. It is shown that NO x adsorber catalyst suffers some loss of its trapping capacity upon high temperature lean-rich exposure. With the use of a disposable SO x trap to remove large portion of the sulfur poisons from the exhaust, the NO x adsorber catalyst can be protected and the numbers of de-sulfation events can be greatly reduced.Spectroscopic techniques, such as DRIFTS and Raman, have been used to monitor the underlying chemical reactions during NO x trapping/ regeneration and de-sulfation periods, and provide a fundamental understanding of NO x storage capacity and catalyst degradation mechanism using model catalysts. This paper examines the sulfur effect on two model NO x adsorber catalysts. The chemistry of SO x /base metal oxides and the sulfation product pathways and their corresponding spectroscopic data are discussed.