Brief Communications in 2011

Congenital disorder of glycosylation-Ia in humans is a multisystemic disease marked by severe neurological deficits and results from deficient glycoprotein processing during development. Christian Körner and his colleagues now show that orally supplying mannose to pregnant dams in a mouse model of the disease is sufficient to ameliorate disease symptoms and early lethality, suggesting a possible therapy to treat this devastating condition.

Spinocerebellar ataxia 1 is a neurodegenerative disease caused by a CAG trinucleotide expansion in the ATXN1 gene encoding the protein ataxin-1. Puneet Opal and his colleagues find that ataxin-1 represses the expression of the angiogenic and neurotrophic factor vascular endothelial growth factor (VEGF) and that VEGF levels are decreased in animals with motor impairment. Overexpression or infusion of VEGF improves motor performance and pathology, suggesting VEGF may have therapeutic potential in this disease.

The placebo response involves a perceived effect of a drug that was not really received by the subject. Fabrizio Benedetti and colleagues demonstrate that the placebo response to NSAIDs in reducing pain is mediated by the endocannabinoid system in humans.

To date, the dogma in the field has been that RANKL, an essential cytokine in osteoclast maturation, is released by osteoblasts as a way to coordinate bone growth and bone loss during adult bone remodeling. Now, Hiroshi Takayanagi and colleagues, as well as Charles O'Brien and colleagues, have independently found that osteocytes are the predominant source of RANKL in the adult mouse. As RANKL signaling is a key target in treating osteoporosis, these results have potentially important implications for disease management.

This report describes the isolation and in vitro expansion of human colon stem cells from normal tissues. Cells with high levels of the membrane receptor EPHB2 are shown to have characteristics of intestinal stem cells, and the authors optimize culture conditions that allow their in vitro expansion as multipotent cells capable of differentiation into several intestinal lineages.

Patients undergoing radiation treatment for Hodgkins's lymphoma are at increased risk of developing secondary malignancies with time. This genome-wide analysis identifies genetic polymorphisms associated with increased risk of secondary malignancies in treated children. The risk alleles result in decreased radiation-mediated induction of PRDM1, a tumor suppressor transcription factor, leading to impaired repression of oncogenic drivers such as MYC.

Snakebite toxins need to be transported through the lymphatic system before gaining access to the blood. By interfering with lymphatic system function, Megan Saul et al. found that nitric oxide donors delay the fatal effects of snake venom in rats. By giving snakebite victims more time to obtain medical care, this approach may be useful for the first-aid treatment of snakebites.

The transcription factor CREB-H has been found to regulate the expression of a suite of genes in mice that are involved in triglyceride metabolism, according to a new study by Ann-Hwee Lee and her colleagues. They also find loss-of-function mutations in the human gene for CREB-H that are associated with highly elevated levels of triglycerides, suggesting a similar role for the protein in humans.

In mice, T regulatory (T_reg) cells show considerable phenotypic and functional plasticity. David Hafler and his colleagues report that the frequency of human T_reg cells expressing IFN-γ is increased in the peripheral blood of individuals with multiple sclerosis. These T_reg cells possess reduced suppressive activity, and in vitro studies suggest that IL-12 promotes the development of a T helper type 1–like phenotype.

Definitive diagnosis of prion disease currently requires postmortem brain tissue. Now, Ryuichiro Atarashi and colleagues have discovered an assay that can identify prions in human cerebrospinal fluid. This assay could allow for diagnosis of disease in living humans.