A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes.

Interleukin-1 beta (IL-1 beta)-converting enzyme cleaves the IL-1 beta precursor to mature IL-1 beta, an important mediator of inflammation. The identification of the enzyme as a unique cysteine protease and the design of potent peptide aldehyde inhibitors are described. Purification and cloning of the complementary DNA indicates that IL-1 beta-converting enzyme is composed of two nonidentical subunits that are derived from a single proenzyme, possibly by autoproteolysis. Selective inhibition of the enzyme in human blood monocytes blocks production of mature IL-1 beta, indicating that it is a potential therapeutic target.     

Effect of phase transitions on compressional-wave velocities in the Earth's mantle

The velocities of seismic waves in the Earth are governed by the response of the constituent mineral assemblage to perturbations in pressure and stress. The effective bulk modulus is significantly lowered if the pressure of the seismic wave drives a volume-reducing phase transformation. A comparison between the amount of time required by phase transitions to reach equilibrium and the sampling period thus becomes crucial in defining the softening and attenuation of compressional waves within such a two-phase zone. These phenomena are difficult to assess experimentally, however, because data at conditions appropriate to the Earth's deep interior are required. Here we present synchrotron-based experimental data that demonstrate softening of the bulk modulus within the two-phase loop of olivine-ringwoodite on a timescale of 100 s. If the amplitude of the pressure perturbation and the grain size are scaled to those expected in the Earth, the compressional-wave velocities within the discontinuities at 410, 520 and, possibly, 660 km are likely to be significantly lower than otherwise expected. The generalization of these observations to aluminium-controlled phase transitions raises the possibility of large velocity perturbations throughout the upper 1,000 km of the mantle.     

Effects of sequential periods of intracranial hypertension on lung fluid balance

Summary Pulmonary hemodynamics and fluid and protein exchange were examined in dogs subjected to three successive periods of intracranial hypertension. Results indicate that the alteration in lung fluid balance is due to increased microvascular surface area following capillary recruitment. The relationship to the mechanism of neurogenic pulmonary edema is discussed.Acknowledgments. Supported in part by grants 79-N17, 80-N105 and 82-N136 from the California Affiliate of the American Heart Association, by a grant from the Strobel Medical Research fund of the American Lung Association of San Francisco and by USPHS GMO7416-2 traineeship (TAJ). The authors thank L. Blount, E. Blount and J. Wong for their assistance.     

Phagosome acidification blocked by intracellular Toxoplasma gondii

Toxoplasma gondii belongs to a group of highly virulent intracellular parasites that reside in host cell vacuoles which resist typical phagosome-lysosome fusion. Live Toxoplasma replicate prodigiously within modified phagocytic vacuoles formed during invagination of the host plasma membrane. In contrast, heat-killed Toxoplasma or specific antibody (heat-inactivated)-coated live Toxoplasma-containing vacuoles readily undergo lysosome fusion and digestion in normal macrophages. Of newly recognized significance to Toxoplasma survival is the microbicidal effect of phagosome acidification, which reportedly can occur independently of fusion with other acidic vesicles. We report here that modified live Toxoplasma-containing vacuoles fail to acidify in normal macrophages, as indicated by the sensitive pH probe fluorescein. In contrast, when live Toxoplasma are coated with specific antibody (heat-inactivated), they trigger phagosome acidification when entering normal macrophages. A similar acidification is observed when normal phagocytes ingest dead Toxoplasma. Extracellular Toxoplasma are highly susceptible to acidic pH conditions, indicating that the acidification block in the modified vacuoles may be important for intracellular survival.     

The strength of Mg(0.9)Fe(0.1)SiO3 perovskite at high pressure and temperature

The Earth's lower mantle consists mainly of (Mg,Fe)SiO3 perovskite and (Mg,Fe)O magnesiowüstite, with the perovskite taking up at least 70 per cent of the total volume. Although the rheology of olivine, the dominant upper-mantle mineral, has been extensively studied, knowledge about the rheological behaviour of perovskite is limited. Seismological studies indicate that slabs of subducting oceanic lithosphere are often deflected horizontally at the perovskite-forming depth, and changes in the Earth's shape and gravity field during glacial rebound indicate that viscosity increases in the lower part of the mantle. The rheological properties of the perovskite may be important in governing these phenomena. But (Mg,Fe)SiO3 perovskite is not stable at high temperatures under ambient pressure, and therefore mechanical tests on (Mg,Fe)SiO3 perovskite are difficult. Most rheological studies of perovskite have been performed on analogous materials, and the experimental data on (Mg,Fe)SiO3 perovskite are limited to strength measurements at room temperature in a diamond-anvil cell and microhardness tests at ambient conditions. Here we report results of strength and stress relaxation measurements of (Mg(0.9)Fe(0.1))SiO3 perovskite at high pressure and temperature. Compared with the transition-zone mineral ringwoodite at the same pressure and temperature, we found that perovskite is weaker at room temperature, which is consistent with a previous diamond-anvil-cell experiment, but that perovskite is stronger than ringwoodite at high temperature.     

Primary visual centers in the frog (Rana esculenta L.) and the problem of ipsilateral projections. Radioautographic study]

The topographic organization of the frog's primary visual system has been reexamined in Rana esculenta using autoradiographic technique. 10 to 24 hrs following an intraocular injection of tritiated proline, an intense labelling was observed contralaterally in the various retinal projection centres (preoptic area); neuropils of Bellonci; corpus geniculatum of the thalamus; posterior thalamus; posterodorsal preoptic area; magnocellular pretectal nucleus and basal optic nucleus; tectal laminae A to G of Potter), as already described. Furthermore, the presence of a ipsilateral projection within the hypothalamus (preoptic area), the thalamus (neuropils of Bellonci and corpus geniculatum) and the pretectium (posterior thalami neuropil, pretectal optic area) is confirmed. On the other hand, the existence of ipsilateral retinotectal (to Potter's lamina F) and retino-tegmentomescencephalic projections (to the basal optic nucleus), which were thusfar questioned, has been demonstrated.