Infant Mesenchymal Stem Cell Insulin Action Is Associated With Maternal Plasma Free Fatty Acids, Independent of Obesity Status: The Healthy Start Study.

Preclinical rodent and nonhuman primate models investigating maternal obesity have highlighted the importance of the intrauterine environment in the development of insulin resistance in offspring; however, it remains unclear if these findings can be translated to humans. To investigate possible intrauterine effects in humans, we isolated mesenchymal stem cells (MSCs) from the umbilical cord tissue of infants born to mothers of normal weight or mothers with obesity. Insulin-stimulated glycogen storage was determined in MSCs undergoing myogenesis in vitro.

Publisher Correction: The CaMKII holoenzyme structure in activation-competent conformations.

This corrects the article DOI: 10.1038/ncomms15742.

Analysis of the CaMKIIα and β splice-variant distribution among brain regions reveals isoform-specific differences in holoenzyme formation.

Four CaMKII isoforms are encoded by distinct genes, and alternative splicing within the variable linker-region generates additional diversity. The α and β isoforms are largely brain-specific, where they mediate synaptic functions underlying learning, memory and cognition. Here, we determined the α and β splice-variant distribution among different mouse brain regions.

DAPK1 Mediates LTD by Making CaMKII/GluN2B Binding LTP Specific.

The death-associated protein kinase 1 (DAPK1) is a potent mediator of neuronal cell death. Here, we find that DAPK1 also functions in synaptic plasticity by regulating the Ca/calmodulin (CaM)-dependent protein kinase II (CaMKII). CaMKII and T286 autophosphorylation are required for both long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory, and cognition.

The CaMKII holoenzyme structure in activation-competent conformations.

The Ca/calmodulin-dependent protein kinase II (CaMKII) assembles into large 12-meric holoenzymes, which is thought to enable regulatory processes required for synaptic plasticity underlying learning, memory and cognition. Here we used single particle electron microscopy (EM) to determine a pseudoatomic model of the CaMKIIα holoenzyme in an extended and activation-competent conformation. The holoenzyme is organized by a rigid central hub complex, while positioning of the kinase domains is highly flexible, revealing dynamic holoenzymes ranging from 15-35 nm in diameter.

CaMKII isoforms differ in their specific requirements for regulation by nitric oxide.

The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) mediates physiological and pathological functions by its Ca(2+)-independent autonomous activity. Two novel mechanisms for generating CaMKII autonomy include oxidation and S-nitrosylation, the latter requiring both Cys280 and Cys289 amino acid residues in the brain-specific isoform CaMKIIα. Even though the other CaMKII isoforms have a different amino acid in the position homologous to Cys280, we show here that nitric oxide (NO)-signaling generated autonomy also for the CaMKIIβ isoform.

IGF-I stimulates Rab7-RILP interaction during neuronal autophagy.

Restoration of autophagy represents a potential therapeutic target for neurodegenerative disorders, but factors that regulate autophagic flux are largely unknown. When deprived of trophic factors, cultured Purkinje neurons die by an autophagy associated cell death mechanism. The accumulation of autophagic vesicles and cell death of Purkinje neurons is inhibited by insulin-like growth factor, by a mechanism that enhances autophagic vesicle turnover.