Volume 24 Issue 1, January 2018

In a recent study of hepatic ischemia–reperfusion injury (IRI), Zhang et al. use tandem 'omics' approaches in mice, pigs, and nonhuman primates to identify lipid metabolic reprogramming as a key determinant of IRI, thus providing novel mechanistic and therapeutic insights.

A Children's Oncology Group study of nearly 1,000 pediatric acute myeloid leukemia (AML) cases reveals marked differences between the genomic landscapes of pediatric and adult AML and offers directions for future work.

One strategy to counter the rise of antimicrobial resistance is the development of vaccines against resistant pathogens, preventing further infection and spread of antimicrobial resistance.

Fry et al. report the first results from a human trial of a CD22-directed chimeric antigen receptor (CAR) T cell therapy providing evidence of efficacy in the treatment of pre–B cell acute lymphoblastic leukemia that is immunotherapy-naive or resistant to CD19-directed CAR T cells.

Through injection of human Alzheimer's disease (AD) brain extracts containing pathological tau protein into transgenic mouse lines harboring different levels of amyloid plaque burden, the authors find that the presence of amyloid plaques modifies endogenous pools of tau protein, creating a unique environment required for the seeding and spreading of distinct tau pathologies.

Thyroid hormone improves mitochondrial function and dynamics in lung epithelium to reduce pulmonary fibrosis in mice.

Degeneration of the retinal pigment epithelium is a hallmark of geographic atrophy, a type of age-related macular degeneration. Kerur et al. show that this degeneration results from a multistep pathway in which mitochondrial dysfunction in RPE cells, triggered by accumulation of Alu RNA, leads to activation of the noncanonical inflammasome via a cGAS–STING–IRF3 signaling axis.

A proteolytically derived fragment of the epigenetic regulator HDAC4 protects the heart through transcriptional repression of the hexosamine biosynthetic pathway, thereby inhibiting protein O-GlcNAcylation and maintaining normal calcium handling and contractility of cardiomyocytes.

ALOX12-mediated generation of 12-HETE leads to GPR31 activation and liver injury in ischemia–reperfusion, which can be targeted in a nonhuman primate model to improve outcome.

The deubiquitinase TNFAIP3 suppresses the kinase ASK1 to ameliorate nonalcoholic fatty liver disease.

In the bone marrow, granulocyte-derived TNFα acts on endothelial cells to maintain the vasculature under steady-state conditions and to promote its regeneration after injury or transplantation.

A comprehensive molecular analysis of almost 1,000 pediatric subjects with acute myeloid leukemia (AML) uncovers widespread differences in pediatric AML as compared to adult AML, including a higher frequency of structural variants and different mutational patterns and epigenetic signatures. Future studies are needed to characterize the functional relevance of these alterations and to explore age-tailored therapies to improve disease control in younger patients.