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Fas is a type I membrane protein and its activation by binding of the Fas ligand or an agonistic anti‐Fas antibody induces apoptosis in Fas‐bearing cells. In this report we prepared lysates from cells treated with anti‐Fas antibody. The lysates induced apoptotic morphological changes in nuclei from normal mouse liver, accompanied by DNA degradation. The apoptosis‐inducing activity was quickly generated in cells by anti‐Fas antibody and was found in the soluble cytosolic fraction. Induction of the activity in cells was inhibited by a tetrapeptide, acetyl‐Tyr‐Val‐Ala‐Asp‐chloromethylketone, a specific inhibitor of interleukin‐1 beta converting enzyme. Addition of COS cell lysates containing Bcl‐2 to the assay significantly inhibited the apoptotic process, indicating that the in vitro process reflected apoptosis that occurs in intact cells.

The dominant minerals in Earth's lower mantle are thought to be Fe-and Al-bearing MgSiO 3 bridgmanite and (Mg,Fe)O ferropericlase 1 . However, experimental measurements of the elasticity of these minerals at realistic lower-mantle pressures and temperatures remain impractical. As a result, di erent compositional models for the Earth's lower mantle have been proposed 2-4 . Theoretical simulations, which depend on empirical evaluations of the e ects of Fe incorporation into these minerals, support a pyrolitic lower mantle that contains a significant amount of ferropericlase 5,6 , much like the Earth's upper mantle. Here we present first-principles computations combined with a lattice dynamics approach that include the e ects of Fe 2+ and Fe 3+ incorporation. We calculate the densities and elastic-wave velocities of several possible lower-mantle compositions with varying amounts of ferropericlase along a mantle geotherm. On the basis of our calculations of aggregate elasticities, we conclude that neither a perovskitic composition (about 9:1 bridgmanite to ferropericlase by volume) nor an olivine-like composition (about 7:3) reproduces the seismological reference model of average Earth properties. However, an intermediate volume fraction (about 8:2) consistent with a pyrolitic composition can reproduce the reference velocities and densities. Bridgmanite that is rich in ferric iron produces the best fit. Our findings support a uniform chemical composition throughout the present-day mantle, which we suggest is the result of whole-mantle convection.Determination of the chemical composition of the lower mantle (LM) has long been one of the central research topics in the deep Earth sciences. The LM composition is key to understanding its dynamical properties. For example, if the LM has a different composition from the upper mantle (UM), these regions convect separately. If the UM and LM have the same composition, then whole-mantle convection is expected 7 . However, physical properties of LM minerals determined from high-pressure (P) and high-temperature (T ) experiments have some uncertainties due to technical difficulties, which give substantial discrepancies on this issue. Several different models have been proposed 2-6,8-15 depending on the research approaches used. Generally, experiments based on the multianvil apparatus propose a pyrolitic LM (refs 2,8,9). In the pyrolite model, a Mg/Si ratio of ∼1.3 is proposed, yielding a notable amount of (Mg,Fe)O ferropericlase (Fp), a solid solution of MgO and FeO together with Fe-and Al-bearing MgSiO 3 bridgmanite (MgBr). A particular composition with the olivine-like Mg/Si ratio as high as 2.0 was however suggested by the equations of state (EoS) measurements using multianvil apparatus with sintered diamonds 3 . An alternative view that the LM is MgBr dominant, corresponding to the perovskitic or chondritic model (Mg/Si ∼ 1.0), is proposed based on diamond-anvil cell experiments 4,10,11 . On the other hand, some geochemical analyses 12,13 suggest layering in the LM in conjunc...

Mutations in particular nucleotides of genes coding for drug targets or drug-converting enzymes lead to drug resistance in Mycobacterium tuberculosis. For rapid detection of drug-resistant M. tuberculosis in clinical specimens, a simple and applicable method is needed. Eight TaqMan minor groove binder (MGB) probes, which discriminate one-base mismatches, were designed (dual-probe assay with four reaction tubes). The target of six MGB probes was the rpoB gene, which is involved in rifampin resistance; five probes were designed to detect for mutation sites within an 81-bp hot spot of the rpoB gene, and one probe was designed as a tuberculosis (TB) control outside the rpoB gene hot-spot. We also designed probes to examine codon 315 of katG and codon 306 of embB for mutations associated with resistance to isoniazid and ethambutol, respectively. Our system was M. tuberculosis complex specific, because neither nontuberculous mycobacteria nor bacteria other than mycobacteria reacted with the system. Detection limits in direct and preamplified analyses were 250 and 10 fg of genomic DNA, respectively. The system could detect mutations of the rpoB, katG, and embB genes in DNAs extracted from 45 laboratory strains and from sputum samples of 27 patients with pulmonary TB. This system was much faster (3 h from DNA preparation) than conventional drug susceptibility testing (3 weeks). Results from the dual-MGB-probe assay were consistent with DNA sequencing. Because the dual-probe assay system is simple, rapid, and accurate, it can be applied to detect drug-resistant M. tuberculosis in clinical laboratories.

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