It has long been noted that while patients with familial hypertrophic cardiomyopathy due to cardiac troponin T (cTnT) mutations often suffer sudden cardiac death, they do not develop significant ventricular hypertrophy, suggesting that a distinct cellular mechanism apart from alterations in myocardial contractility is responsible. A new study has revealed that a single missense mutation in cTnT causes a striking disruption to energy metabolism, leading to cardiomyopathy.
Ketty Schwartz, Jean-Jacques Mercadier
A new study demonstrates that angiotensin-induced hypertension results in a marked decrease in expression of the β subunit of the BK channel, suggesting a role for this critical subunit in the regulation of vascular tone.
Michael Kotlikoff, Ian Hall
Bacillus anthracis, the causative agent of anthrax, is believed to induce disease and death in humans in an endotoxic shock–like manner. A comprehensive study of the effects of anthrax toxin in mice demonstrates that toxin-induced death is mediated not by cytokine release, as previously thought, but by hypoxia-induced liver failure. The study strongly suggests that the therapies developed for treatment of cytokine-mediated septic shock will not be appropriate for the treatment of anthrax.
Alice S. Prince
In an unusual paradox, asthmatics who are chronically treated with bronchodilating β-agonists sometimes experience a worsening of their condition. A new study describes one possible mechanism and reveals a potential new therapeutic target in the treatment of asthma.
Stephanie A. Shore, Jeffrey M. Drazen
Thyroid hormones are critical for differentiation, growth, and metabolism. A new study investigating the biological role of the TH receptor TR-β has demonstrated that DNA binding is critical for most of its functions, but also suggests that novel mechanisms independent of DNA binding may contribute to regulation of auditory function by TR-β.
Mitchell A. Lazar
The cell-surface associated molecule Cripto is overexpressed in a wide range of epithelial cancers, yet little is known about potential mechanisms by which Cripto expression might enhance tumorigenesis. A new study reveals that binding of Cripto to the TGF-β ligand Activin B can block Activin B–mediated suppression of cell proliferation. Furthermore, this study also demonstrates that antibody blockade of Cripto function may prove useful in the inhibition of tumorigenesis.
Michael M. Shen
Hepatitis delta virus (HDV) is a cause of acute and chronic liver disease for which no effective therapy is currently available. Previous research has demonstrated that prenylation of the large HDV antigen is essential for viral assembly. A new report describes a novel small animal model for HDV replication and demonstrates that prenylation inhibitors are highly effective at clearing viremia and thus have potential relevance for the treatment of chronic delta hepatitis.
Theo Heller, Jay H. Hoofnagle
Alzheimer disease (AD) is characterized by the progressive accumulation of amyloid β protein (Aβ) in areas of the brain serving cognitive functions such as memory and language. The first of two separate reports (see the related articles beginning on pages 415 and 440) reveals that intrinsic T cell reactivity to the self-antigen Aβ exists in many humans and increases with age. This finding has implications for the design of Aβ vaccines. The second report demonstrates that a number of FDA- approved nonsteroidal anti-inflammatory drugs are capable of lowering Aβ levels in mice. The work suggests that further testing of the therapeutic utility of these types of compounds for the potential treatment of AD is warranted.
John R. Cirrito, David M. Holtzman
Endocannabinoids, endogenous ligands of cannabinoid receptor type 1 (CB1), have emerged as novel and important regulators of energy homeostasis. A report in this issue demonstrates reduced body weight, fat mass, and appetite in CB1–/– mice. Examination of the underlying mechanisms reveals a dual role for endocannabinoids as they affect both appetite and peripheral lipolysis.
Tamas L. Horvath
A delicate balance exists between ECM synthesis and degradation such that interruption of the corresponding pathways results in increased plasminogen activator inhibitor-1 (PAI-1), pathological matrix accumulation, and glomerulosclerosis. A new study demonstrates that therapy with a mutant PAI-1 increases matrix turnover and reduces glomerulosclerosis by competing with endogenous PAI-1, suggesting therapeutic utility in the treatment of fibrotic renal disease.
Agnes B. Fogo
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