Tumour-necrosis factor-alpha (TNF-alpha) is a cytokine that contributes to a variety of inflammatory disease states. The protein exists as a membrane-bound precursor of relative molecular mass 26K which can be processed by a TNF-alpha-converting enzyme (TACE), to generate secreted 17K mature TNF-alpha. We have purified TACE and cloned its complementary DNA. TACE is a membrane-bound disintegrin metalloproteinase. Structural comparisons with other disintegrin-containing enzymes indicate that TACE is unique, with noteable sequence identity to MADM, an enzyme implicated in myelin degradation, and to KUZ, a Drosophila homologue of MADM important for neuronal development. The expression of recombinant TACE (rTACE) results in the production of functional enzyme that correctly processes precursor TNF-alpha to the mature form. The rTACE provides a readily available source of enzyme to help in the search for new anti-inflammatory agents that target the final processing stage of TNF-alpha production.

Abstract. Structural and thermochronological investigations of southern Tibet (Xizang) suggest that intracontinental thrusting has been the dominant cause for formation of thickened crust in the southernmost Tibetan plateau since late Oligocene. Two thrust systems are documented in this study: the north dipping Gangdese system (GTS) and the younger south dipping Renbu-Zedong system ( RZT). West of Lhasa, the Gangdese thrust juxtaposes the Late Cretaceous forearc basin deposits of the Lhasa Block (the Xigaze Group) over the Tethyan sedimentary rocks of the Indian plate, whereas east of Lhasa, the fault juxtaposes the Late Cretaceous-Eocene, Andean-type arc (the Gangdese batholith) over Tethyan sedimentary rocks. Near Zedong, 150 km southeast of Lhasa, the Gangdese thrust is marked by a >200-m-thick mylonitic shear zone that consists of deformed granite and metasedimentary rocks. A major south dipping backthrust in the hanging wall of the Gangdese thrust puts the Xigaze Group over Tertiary conglomerates and the Gangdese plutonics north of Xigaze and west of Lhasa. A lower age bound for the Gangdese thrust of 18.3±0.5 Ma is given by crosscutting relationships. The timing of slip on the Gangdese thrust is estimated to be 27-23 Ma from 40 Ar/ 39 Ar thermochronology, and a displacement of at least 46±9 km is indicated near Zedong. The age of the Gangdese thrust (GT) is consistent with an upper age limit of -24 Ma for the initiation of movement on the Main Central thrust. In places, the younger Renbu-Zedong fault is thrust over the trace of the GT, obscuring its exposure. The RZT appears to have been active at circa 18 Ma but had ceased movement by 8±1 Ma. The suture between India and Asia has been complexly modified by development of the GTS, RZT, and, locally, strike-slip and normal fault systems.

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The Diancang Shan, a horst massif within the Red River fault zone in Yunnan, People's Republic of China, preserves a structural, petrological, and thermal record of two distinct phases of tectonic activity: a left-lateral ductile shear that terminated between 20 and 17 Ma and a ductile-to-brittle phase of normal faulting which began at 4.7 Ma and remains active. Mylonitic rocks in the core of the range display an early, steep, hightemperature (HT), schistosity and a horizontal stretching lineation that are both parallel to the trend of the belt. Kinematic indicators indicate that shear was left-lateral. The complex shape of the HT schistosity at the southern termination of the massif likely results from a large-scale, oblique, left-lateral C' shear plane that dismembered the shear zone and separated the Ailao Shan and the Diancang Shan as left-lateral deformation terminated. Thermochronological and thermobarometric results suggest that the gneisses were partially unroofed during this event. Along the eastern edge of the Diancang Shan, the HT fabrics were overprinted by low-temperature structures during activation of east dipping normal faults. Cooling associated with this normal/right-lateral faulting along the Diancang Shan (and perhaps activation of the right-lateral/normal movement on the Range Front fault farther south along the Ailao Shan) began at 4.7:50.1 Ma. These results tend to support the view that extrusion of Indochina occurred along the left-lateral Red River shear zone between 35 and 19-17 Ma. Initiation of right-lateral/normal slip during the late Miocene may relate to eastward extensional collapse of the thickened Tibetan crust or, more probably, to initiation of the second phase of extrusion. ment has been thrust to the southwest over the Indochina sedimentary series [e.g., Duan and 2hao, 1981; Chen•l, 1987]. In the continental extrusion hypothesis, the South China Sea is interpreted to be a pull-apart basin at the southeast termination of the Red River shear zone (Figure 1) that opened as a result of left-lateral strikeslip motion [Tapponnier et al., 1982, 1986; Peltzer and Tapponnier, 1988]. Calculation of poles of rotation and rates of seafloor spreading based on seafloor magnetic anomalies suggest a total left-lateral offset along the Red River shear zone of about 550 krn between 32 and .-.16 Ma [Briais, 1989; Briais et al., 1993]. Recent studies have tended to confirm many of the predictions of the extrusion model and support the interpretation that the Red River fault zone is a Tertiary, intracontinental, ductile, strike-slip shear zone with at least 500 km of left-lateral offset [Tapponnier et al., 1990; Sch•rer 1990, Leloup et al., 1990; Lacassin et al., 1991; Harrison et al., 1992a]. This fault alone may have absorbed up to •20% of the collision-related deformation affecting Asia [Lacassin et al., 1991; Leloup, 1991]. The three 10-to 20-km-wide massifs in southern Yunnan that define the Red River shear zone, the Ailao Shah, Diancang Shan, and Xuelong Shan (the ADX shear zone), consist o...

MC4R and MC5R exhibit evidence of linkage or association with obesity phenotypes, but this evidence is strongest for MC5R.

Recent work has tended to support the view that laterM extrusion of Indochlna along the Red l•ver fault zone was a significant factor in accommodating the convergence of India with Asia. To better understand the nature and timing of this feature, 4øAr/39Ar age spectrum analyses were undertaken on minerals from the Ailao Shah/Red l•ver metamorphic belt in southern Yunnan, China. Interpreted using diffusion domain theory, these results yield thermal histories in thetemperature range 550-150øC. Discontinuities in cooling rates observed from these results suggest a transition in deformation style in the shear zone during the early Miocene. At least in the vicinity of our samples, left-lateral, strike-slip ductile deformation appears to have ceased by about 20 Ms. The mylonitic gneisses in the shear zone were subsequently obliquely unroofed, probably due to a component of normal faulting along the eastern edge of the shear zone causing a brief (locally <1 m.y.) but rapid (>100øC/m.y.) cooling episode. This transition may have resulted from a component of northeast-southwest extension attributable to greater clockwise rotation of Indochina relative to South China after ~20 Ma than that consistent with pure strike-slip along the fault. K-At ages on clay minerals from gouge witkin the normal faults bounding the Ailao Shah and Diancang Shah yield a r•nge of ages between 20 and 185 Ma but show a significant clustering at 20-25 Ms. These results suggest that early Miocene movement on a precursor to the Range Front norraM fault in the Ailao Shah caused oblique unroofmg of the shear zone. This early Miocene event corresponds in time with a transition from low to very high denudation rates throughout the HimMaya and southern Tibet. This coincidence may reflect that once left-laterM strike-slip motion on the Red l•ver fault zone slowed or was terrainsted, accommodation of much of the continued northward convergence of India occurred on the Main Central Thrust resulting in rapid uplift in the Tethyo•n Himalaya and Gangdese belt. subject of lively debate [e.g., Peltzer and Tapponnier, 1988; England and Molnar, 1990; Monastersky, 1990]. Although once a subject of dispute [e.g., Dewey et al., 1989], recent work has confirmed that the Ailao Shah/Red River metamorphic belt in southern Yunnan, China, was a left-lateral, ductile strike-slip shear zone during the mid-Tertiary [ Tapponnier et al., 1986, 1990; Schaefer et al., 1990; Leloup, 1991]. The sense of shear in the gneisses, mylonites, and elongated granite pods exposed in the core of the Ailao Shah and Diancang Shah, which parallel the Red River fault zone for about 600 km, is left-lateral (Figure 1). Deformed anatectic granitoids in the Ailao Shah yield U-Pb mineral ages of 23.0-4-0.2 Ma [Schaefer et al., 1990] providing an upper limit for the cessation of ductile behavior within this portion of the shear zone. Tapponnier et al. [1990] suggest that the total amount of Tertiary left-lateral offset may have been in excess of 500 km. The present-day sense of movement on the active ...

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