We determined the structure of the human mGlu(1) receptor seven-transmembrane (7TM) domain bound to a negative allosteric modulator, FITM, at a resolution of 2.8 angstroms. The modulator binding site partially

overlaps with the orthosteric binding sites of class A GPCRs but is more restricted than most other GPCRs. We observed a parallel 7TM dimer mediated by cholesterols, which suggests that signaling initiated by glutamate’s interaction with the extracellular domain might be mediated via 7TM interactions within the full-length receptor dimer. A combination of crystallography, structure-activity relationships, mutagenesis, and full-length dimer modeling provides insights about the allosteric modulation and activation mechanism of class C GPCRs.”
“Background Imbalance between the parasympathetic and sympathetic nervous systems BMS 345541 is a recognized contributor to progression of chronic heart failure. Current therapy with beta adrenergic antagonists is designed to moderate the up-regulation of norepinephrine and sympathetic

effects; however, to date, there are no therapies that specifically address the withdrawal of parasympathetic influences on cardiac function and structure.\n\nMethods/Results In order to evaluate the impact of vagus nerve stimulation, an international multi-center randomized clinical trial (INOVATE-HF) has been designed to assess safety and efficacy of vagus nerve stimulation in symptomatic patients TGF-beta pathway with heart failure on optimal medical therapy using the CardioFit System (BioControl Medical, Yehud, Israel). Up to 650 patients from 80 sites will be recruited and GDC-0068 in vitro randomized in a 3:2 ratio to receive active treatment or standard optimal medical therapy. Inclusion criteria include left ventricular systolic dysfunction, the presence of New York Heart Association Class III symptoms, sinus rhythm, and QRS width less than 120 milliseconds. The study is powered to detect differences in the primary efficacy end point of all-cause mortality and heart failure hospitalization and 2 safety end points.\n\nConclusion Vagal nerve stimulation with CardioFit as a treatment for symptomatic heart failure

is under active investigation as a novel approach to restore balance between the sympathetic and parasympathetic nervous systems. If shown to be safe and effective in decreasing heart failure events and mortality, this novel approach will impact the treatment paradigm for heart failure. (Am Heart J 2012;163:954-962.e1.)”
“Brooding of egg masses by a squid in Japan is described. Brooding females were photographed in situ, and the females, their eggs, and their hatchlings were collected. The squid had all undergone gelatinous degeneration and swam slowly and continuously by undulating the fins and expelling water sporadically through the funnel. Eggs were held together by a dark, viscous material that formed a single-layer, sheet-like mass, from which hatchlings were seen to emerge.