Volume 20 Issue 10, October 2014

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. A new study has shown that the lipid lactosylceramide, produced by astrocytes, contributes to disease progression in a mouse model of MS.

Altered stem cell homeostasis underlies functional tissue decline during muscle aging and disease progression. Janus kinase–signal transducer and activator of transcription (JAK-STAT) signal transduction is a crucial regulator of muscle regeneration, and targeting this pathway in mice relieves aspects of debilitating muscle wasting.

A new study identifies recurrent somatic duplications of a NOTCH1-driven enhancer of MYC in human T cell leukemia. This enhancer is required for both normal and malignant T cell development.

A new study shows that plasma levels of branched-chain amino acids are elevated in subjects several years before they are diagnosed with pancreatic cancer. This may reflect breakdown of peripheral protein stores in the early stages of the disease.

Alzheimer's disease is characterized by severe cognitive decline and brain amyloid plaques. A new study in mouse models that develop features of Alzheimer's disease indicates that progranulin may have a role in clearing these plaques.

Targeted genome editing by engineered endonucleases allows the precise introduction of gene deletions and substitutions into the target genome. In 'Bench to Bedside', Keith Joung and his colleagues discuss how genome-editing technologies could be applied to engineer disease-associated somatic variation into human cell lines and disease models. This would allow the functional interpretation of such variants, which could then be applied to molecular diagnostics in the clinic. In 'Bedside to Bench', Angelo Lombardo and Luigi Naldini consider the potential applications of genome editing in the clinic, in which engineered endonucleases have been shown to be safe. Endonucleases could replace disease-associated genes with wild-type versions or be used to delete genes encoding receptors essential to viral host entry to prevent infection.

Peter Walter, Professor at the University of California, San Francisco (UCSF), and Kazutoshi Mori, Professor at Kyoto University, share the 2014 Lasker Basic Medical Research Award for their work that resulted in identification of key components of the unfolded protein response (UPR). Walter identified the IRE1 component of the UPR in 1993, shortly after starting his laboratory at UCSF.

Kazutoshi Mori, Professor at Kyoto University, shares the 2014 Lasker Basic Medical Research Award with Peter Walter, Professor at the University of California, San Francisco. Walter and Mori are honored for their work identifying core components of the unfolded protein response (UPR). Mori made his first major discovery in this area—identification of the IRE1 component of the UPR—in 1993, while he was a postdoctoral fellow at the University of Texas Southwestern Medical Center.

Mahlon DeLong, Professor at Emory University School of Medicine, shares the 2014 Lasker∼DeBakey Clinical Medical Research Award with Alim Louis Benabid, Chairman of the Board at Clinatec Institute in Grenoble, France. DeLong and Benabid are honored for their work that led to the development of deep brain stimulation, a therapy that has helped relieve symptoms in thousands of patients with advanced Parkinson's disease.

Alim Louis Benabid, Chairman of the Board at Clinatec Institute in Grenoble, France shares the 2014 Lasker∼DeBakey Clinical Medical Research Award with Mahlon DeLong, Professor at Emory University School of Medicine. DeLong and Benabid are honored for their work that led to the development of deep brain stimulation, a therapy that has helped relieve symptoms in thousands of patients with advanced Parkinson's disease.

Mary-Claire King, American Cancer Society Professor of Medicine and Genome Sciences at the University of Washington, Seattle, is recognized with the 2014 Lasker∼Koshland Special Achievement Award for her wide range of contributions to biology and medicine as well as human rights. King's development of mathematical models of genetics and discovery of the role that a single gene locus, BRCA1, has in hereditary breast cancer have had wide influence, and she has worked tirelessly to apply genetics to reunite missing persons, such as the 'lost children' of Argentina, with their families.

A chimpanzee adenovirus-based vaccination approach elicits acute and long-term protection against ebolavirus challenge in nonhuman primates.

A long-range MYC enhancer is duplicated in human T-ALL and is required for T cell development and NOTCH1-induced leukemogenesis.

An in vivo RNAi dropout screen identifies Mapk14 as a new mediator of sorafenib resistance in hepatocellular carcinoma, and Mapk14 inhibition both improves sorafenib therapy and restores sensitivity to sorafenib-resistant tumors.

In multiple sclerosis and experimental autoimmune encephalomyelitis, astrocytes produce lactosylceramide, a glycolipid that promotes astrocyte and microglial activation and immune cell infiltration into the CNS.

Progranulin overexpression in Alzheimer's disease model mice protects against neuronal loss and enhances cognitive deficits.

The G protein–coupled receptor F2rl1 translocates from the plasma membrane to the nucleus of retinal ganglion neurons to control Vegfa expression and retinal angiogenesis.

In two new reports, STAT3 signaling is shown to be increased in adult muscle satellite cells, and its inhibition improves muscle regeneration.

In two new reports, STAT3 signaling is shown to be increased in adult muscle satellite cells, and its inhibition improves muscle regeneration.

Genetic deletion of the lysosomal Ca2+ channel MCOLN1 in mice results in muscular dystrophy, implicating this source of calcium in muscle membrane repair.

Elevated plasma levels of branched chain amino acids detected prior to pancreatic cancer diagnosis may result from whole body tissue breakdown occurring during the early stages of this disease.

Rampias et al. report that inactivating mutations in Notch pathway components are frequent in human bladder cancer and drive bladder tumorigenesis in mice.

Gibbons et al. show that T cells in newborns, previously thought to have a limited ability to fight infection, can produce interleukin-8, an effector of innate immunity.

External blood-cleansing device for rapidly removing microorganisms and endotoxins from blood without first needing to identify the source of the infection.