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Dysfunction of the dopamine neurotransmitter system has long been implicated in depression. Now, Fang Liu and colleagues show that the interaction between two dopamine receptor subtypes is increased in the brain of subjects with major depression. Blocking this interaction in rodent models of depression can result in antidepressant-like effects.
Dry mucosal surfaces, such as the eyes and mouth, are a major clinical problem, particularly in the elderly or in individuals taking certain medications. Now, Carlos Belmonte and his colleagues show that cooling of the eye, caused by surface evaporation during eye opening, can induce tearing by stimulating TRPM8-expressing cold-sensing nerve endings.
Infectious hepatitis C virus (HCV) particles assemble near lipid droplets in infected cells. Herker et al. now report that diacylglycerol acyltransferase-1 (DGAT1) is required for this process and show that inhibiting DGAT1 reduces HCV infectivity in vitro. Targeting DGAT1 might offer a new strategy for the control of HCV infection.
Passive transfer of high doses of neutralizing antibodies can protect nonhuman primates against infection with simian HIV (SHIV). Ng et al. now report that low levels of neutralizing polyclonal antibodies plus a neutralizing monoclonal antibody do not prevent infection with SHIV, but do delay peak viremia, modulate CD4+ T cell decline and promote the de novo generation of neutralizing antibodies in macaques.
The rapid mutation rate of HIV-1 enables its escape from neutralizing antibodies (NAbs) in infected individuals. Bunnik et al. now show that the immune pressure exerted by NAbs has, over the course of the HIV epidemic, altered the HIV-1 envelope glycoprotein such that HIV-1 variants isolated from recently infected individuals are more resistant to NAbs, compared with viral variants isolated from individuals infected at the start of the epidemic. Their results suggest the need to carefully select the envelope gene used in today's vaccine efforts.
Mutations in the kinase LRRK2 have been linked to Parkinson's disease. Now, Ted Dawson and his colleagues have identified inhibitors of LRRK2 that can reduce LRRK2-induced neurotoxicity in cell culture and in mice.
Ebola and Marburg viruses cause lethal hemorrhagic fevers for which there are presently no licensed preventive or curative antiviral agents. In a new report, Warren et al. show that positively charged phosphorodiamidate morpholino oligomers administered shortly after viral infection can protect nonhuman primates from this frequently fatal disease.
Ethylmalonic encephalopathy is a metabolic disease affecting many organ systems that is caused by the inability to metabolize sulfide. Now, Zeviani and colleagues have discovered a dual drug regimen that can ameliorate disease in affected children.
Proper body weight is determined by orexigenic and anorexigenic neurons in the hypothalamus. Lori Zeltser and her colleagues have found that a subset of neurons in the developing hypothalamus expressing a potent orexigenic hormone is derived from precursors expressing an anorexigenic hormone. These results suggest that developing feeding circuits are more plastic than previously thought and give rise to new concerns about the effects of a mother's diet during pregnancy on her offspring.
