Sleep-wake body temperature regulates tau secretion in mice and correlates with CSF and plasma tau in humans.

The sleep-wake cycle regulates interstitial fluid and cerebrospinal fluid (CSF) tau levels in both mouse and human by mechanisms that remain unestablished. Here, we reveal a novel pathway by which wakefulness increases extracellular tau levels in mouse and humans. In mice, higher body temperature (BT) associated with wakefulness and sleep deprivation increased CSF tau.

Evidence for the spread of human-derived mutant huntingtin protein in mice and non-human primates.

In recent years, substantial evidence has emerged to suggest that spreading of pathological proteins contributes to disease pathology in numerous neurodegenerative disorders. Work from our laboratory and others have shown that, despite its strictly genetic nature, Huntington's disease (HD) may be another condition in which this mechanism contributes to pathology. In this study, we set out to determine if the mutant huntingtin protein (mHTT) present in post-mortem brain tissue derived from HD patients can induce pathology in mice and/or non-human primates.

Efficient parallel synthesis of macrocyclic peptidomimetics.

A new method for solid phase parallel synthesis of chemically and conformationally diverse macrocyclic peptidomimetics is reported. A key feature of the method is access to broad chemical and conformational diversity. Synthesis and mechanistic studies on the macrocyclization step are reported.

Expression of constitutively active guanylate cyclase in cardiomyocytes inhibits the hypertrophic effects of isoproterenol and aortic constriction on mouse hearts.

Evidence from several rodent models has suggested that a reduction of either atrial natriuretic peptide or its receptor in the heart affects cardiac remodeling by promoting the onset of cardiac hypertrophy. The atrial natriuretic peptide receptor mediates signaling at least in part via the generation of intracellular cyclic GMP. To directly test whether accumulation of intracellular cyclic GMP conveys protection against cardiac hypertrophy, we engineered transgenic mice that overexpress a catalytic fragment of constitutively active guanylate cyclase domain of the atrial natriuretic peptide receptor in a cardiomyocyte-specific manner.