Autophagy–physiology and pathophysiology

“Autophagy” is a highly conserved pathway for degradation, by which wasted intracellular macromolecules are delivered to lysosomes, where they are degraded into biologically active monomers such as amino acids that are subsequently re-used to maintain cellular metabolic turnover and homeostasis. Recent genetic studies have shown that mice lacking an autophagy-related gene (Atg5 or Atg7) cannot survive longer than 12 h after birth because of nutrient shortage. Moreover, tissue-specific impairment of autophagy in central nervous system tissue causes massive loss of neurons, resulting in neurodegeneration, while impaired autophagy in liver tissue causes accumulation of wasted organelles, leading to hepatomegaly. Although autophagy generally prevents cell death, our recent study using conditional Atg7-deficient mice in CNS tissue has demonstrated the presence of autophagic neuron death in the hippocampus after neonatal hypoxic/ischemic brain injury. Thus, recent genetic studies have shown that autophagy is involved in various cellular functions. In this review, we introduce physiological and pathophysiological roles of autophagy

Measurements of the semileptonic decays B̄→Dν̄ and B̄→D*ν̄ using a global fit to DXν̄ final states

Semileptonic B̄ decays to DXν̄ (=e or μ) are selected by reconstructing D0 and D+ combinations from a sample of 230×106 Υ(4S)→BB̄ decays recorded with the BABAR detector at the PEP-II e+e- collider at SLAC. A global fit to these samples in a three-dimensional space of kinematic variables is used to determine the branching fractions B(B-→D0ν̄)=(2.34±0.03±0.13)% and B(B-→D *0ν̄)=(5.40±0.02±0.21)% where the errors are statistical and systematic, respectively. The fit also determines form-factor parameters in a parametrization based on heavy quark effective theory, resulting in ρD2=1.20±0.04±0.07 for B̄→Dν̄ and ρD*2=1.22±0.02±0.07 for B̄→D*ν̄. These values are used to obtain the product of the Cabibbo-Kobayashi-Maskawa matrix element |Vcb| times the form factor at the zero recoil point for both B̄→Dν̄ decays, G(1)|Vcb|=(43.1±0.8±2.3) ×10-3, and for B̄→D*ν̄ decays, F(1)|Vcb|=(35.9±0.2±1.2)×10-3. © 2009 The American Physical Society