Lethal Disorder of Mitochondrial Fission Caused by Mutations in DNM1L.

We describe two infants with hypotonia, absent respiratory effort, and giant mitochondria in neurons due to compound heterozygosity for 2 nonsense mutations of DNM1L. DNM1L has a critical role in regulating mitochondrial morphology and function. This observation confirms the central role of mitochondrial fission to normal human development.

Spell Checking Nature: Versatility of CRISPR/Cas9 for Developing Treatments for Inherited Disorders.

Clustered regularly interspaced short palindromic repeat (CRISPR) has arisen as a frontrunner for efficient genome engineering. However, the potentially broad therapeutic implications are largely unexplored. Here, to investigate the therapeutic potential of CRISPR/Cas9 in a diverse set of genetic disorders, we establish a pipeline that uses readily obtainable cells from affected individuals.

Stem cells on alert: priming quiescent stem cells after remote injury.

A recent paper published by Rodgers et al. describes a novel phase of stem cell quiescence, termed GAlert, that serves to prime cells in response to injury-induced signals. These stem cells are located distal to the site of injury and require mTORC1 activity to elicit the alert response.

Pre-B cell colony-enhancing factor (PBEF/Nampt/visfatin) primes neutrophils for augmented respiratory burst activity through partial assembly of the NADPH oxidase.

Pre-B cell colony-enhancing factor ([PBEF] also known as Nampt/visfatin) is a pleiotropic 52-kDa cytokine-like molecule whose activity has been implicated in multiple inflammatory disease states. PBEF promotes polymorphonuclear neutrophil (PMN) proinflammatory function by inhibiting constitutive PMN apoptosis. We investigated whether PBEF activates or primes for PMN respiratory burst.

Pre-B cell colony-enhancing factor (PBEF)/visfatin: a novel mediator of innate immunity.

Pre-B cell colony-enhancing factor (PBEF), also known as visfatin, is a highly conserved, 52-kDa protein found in living species from bacteria to humans. Originally a curiosity identified serendipitously in microarray studies but having no obvious functional importance, PBEF has now been shown to exert three distinct activities of central importance to cellular energetics and innate immunity. Within the cell, PBEF functions as a nicotinamide phosphoribosyl transferase, the rate-limiting step in a salvage pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis.

Modulating neutrophil apoptosis.

Polymorphonuclear neutrophils are short-lived phagocytic cells that serve as cardinal early cellular effectors of innate immunity. Both oxidative and non-oxidative mechanisms contribute to microbial killing by the neutrophil. Neutrophil defence mechanisms are potent but non-specific, with the result that inadvertent injury to host tissues commonly accompanies the activation of a neutrophil mediated response; this bystander injury has been implicated in the tissue injury of sepsis.