Volume 20 Issue 12, December 2014

Our list of newsmakers this year includes a range of nonconformists, from a scientist advocating population-wide genetic tests to a doctor who caused a stir while waiting for takeout food.

At first glance, 2014 may seem like a year dominated by disease outbreaks, from polio's reemergence in parts of Asia to the Ebola epidemic that still continues to make headlines. But a closer look indicates 2014 was replete with regulatory rulings, big investments in genomic medicine and activism in the name of research funding.

This year's most notable research included studies that opened new avenues for regenerative medicine, paved the way to editing out vulnerability to disease and unraveled the genetic complexities underlying diseases such as leukemia and schizophrenia. Here are some of the papers that captured our attention and moved their fields forward in 2014.

This year's newsworthy drugs made major strides against infectious diseases, cancer and more. Some others received attention for controversies they stemmed or stomped. Here is a look at the therapies that leapt forward, some that are in limbo, and others that fell by the wayside.

Diffuse intrinsic pontine glioma is a uniformly lethal malignant tumor of infancy with no effective therapies. A new study reveals that inhibition of JMJD3 has robust antitumor activity in diffuse intrinsic pontine glioma xenografts.

Increasing evidence points to a role for the immune system in the regulation of metabolism. Two new studies in mice indicate treatment with interleukin-22 restores mucosal immunity in diabetes and alleviates metabolic disease, resulting in improved glycemic control.

Frontotemporal dementia (FTD) is a neurodegenerative disease that causes social dysfunction and other symptoms. A new study suggests that social dysfunction in FTD is due to decreased microRNA-124 expression and resulting changes in glutamate receptor composition in the prefrontal cortex.

Vascular endothelial growth factor A (VEGF-A) is a potent proangiogenic cytokine elevated in patients with peripheral artery disease (PAD). A new study links impaired vascular regrowth in PAD to increased expression of an antiangiogenic splice variant of VEGF-A.

Understanding the regenerative capacity of the adult mammalian heart and the cell types involved is essential for developing therapies for cardiac repair.

Hashizume et al. report a new therapeutic strategy for treating pediatric gliomas with mutations in the H3F3A gene by inhibiting histone demethylation.

Aftab Ansari and his colleagues show that antibody-mediated masking of α4β7 integrin impedes intravaginal transmission of simian immunodeficiency virus in macaques.

The authors delineate a new pathway that regulates apoptosis, involving the known proapoptotic kinase PKCD, as well as the ubiquitin ligase Fbox protein FBXO25 and the mitochondrial antiapoptotic factor HAX-1, and report its alteration during lymphomagenesis.

Mutations in the costimulatory molecule CTLA-4 in six families are associated with immune dysregulation.

A new study reveals the identity of proinflammatory and anti-inflammatory cytokines that influence beta cell stress and thus glucose tolerance.

Obesity-induced mitochondria stress and dysfunction results from disorganized mitochondria-associated ER membranes and excess calcium flux.

The brown fat-derived neuregulin 4 regulates hepatic lipid homeostasis and whole-body insulin sensitivity

A new mouse model of frontotemporal dementia is described in which the mice show miR-124– and AMPA receptor–mediated social behavioral deficits.

Mutations in UNC5C are identified in individuals with late-onset Alzheimer's disease and increase susceptibility of neurons to cell death.

Immune complexes from mouse models of systemic lupus erythematosus and from humans with the disease promote dendritic cell migration in vivo.

Alternative splicing of the gene encoding VEGF-A under ischemic conditions generates an antiangiogenic isoform of the protein that impairs revascularization under conditions of metabolic dysfunction in mice, and this isoform is found at elevated levels in patients with peripheral artery disease.

Systematic analysis of cancer-associated mutations in the blood cells of healthy individuals.

Scalable and rapid target enrichment method for next-generation sequencing of clinical-grade, formalin-fixed paraffin-embedded cancer samples.

Longitudinal PET-MRI study on the dynamics of β-amyloid deposition and regional cerebral blood flow in the Alzheimer's disease mouse brain.