Genetic susceptibility to diabetic kidney disease is linked to promoter variants of XOR.

The lifetime risk of kidney disease in people with diabetes is 10-30%, implicating genetic predisposition in the cause of diabetic kidney disease (DKD). Here we identify an expression quantitative trait loci (QTLs) in the cis-acting regulatory region of the xanthine dehydrogenase, or xanthine oxidoreductase (Xor), a binding site for C/EBPβ, to be associated with diabetes-induced podocyte loss in DKD in male mice. We examine mouse inbred strains that are susceptible (DBA/2J) and resistant (C57BL/6J) to DKD, as well as a panel of recombinant inbred BXD mice, to map QTLs.

Gene expression profiles in sporadic ALS fibroblasts define disease subtypes and the metabolic effects of the investigational drug EH301.

Metabolic alterations shared between the nervous system and skin fibroblasts have emerged in amyotrophic lateral sclerosis (ALS). Recently, we found that a subgroup of sporadic ALS (sALS) fibroblasts (sALS1) is characterized by metabolic profiles distinct from other sALS cases (sALS2) and controls, suggesting that metabolic therapies could be effective in sALS. The metabolic modulators nicotinamide riboside and pterostilbene (EH301) are under clinical development for the treatment of ALS.

Sex and oestrogen receptor β have modest effects on gene expression in the mouse brain posterior cortex.

Introduction: Sex differences in brain cortical function affect cognition, behaviour and susceptibility to neural diseases, but the molecular basis of sexual dimorphism in cortical function is still largely unknown. Oestrogen and oestrogen receptors (ERs), specifically ERβ, the most abundant ER in the cortex, may play a role in determining sex differences in gene expression, which could underlie functional sex differences. However, further investigation is needed to address brain region specificity of the effects of sex and ERβ on gene expression.

Raloxifene is a Female-specific Proteostasis Therapeutic in the Spinal Cord.

Several neurodegenerative disorders are characterized by proteasome dysfunctions leading to protein aggregations and pathogenesis. Since we showed that estrogen receptor alpha (ERα) activates the proteasome, drugs able to stimulate ERα in the central nervous system (CNS) could hold potential for therapeutic intervention. However, the transcriptional effects of selective estrogen receptor modulators (SERMs), such as tamoxifen and raloxifene, can be tissue specific.

Identification of MALT1 feedback mechanisms enables rational design of potent antilymphoma regimens for ABC-DLBCL.

MALT1 inhibitors are promising therapeutic agents for B-cell lymphomas that are dependent on constitutive or aberrant signaling pathways. However, a potential limitation for signal transduction-targeted therapies is the occurrence of feedback mechanisms that enable escape from the full impact of such drugs. Here, we used a functional genomics screen in activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) cells treated with a small molecule irreversible inhibitor of MALT1 to identify genes that might confer resistance or enhance the activity of MALT1 inhibition (MALT1i).