The evolution of depletion zones beneath mud volcanoes

Depletion zones are the least well understood component of mud volcanic systems. They are generally difficult to image using reflection seismic data, and have only rarely been identified and described in the subsurface. This study documents 277 mapped depletion zones in the western Nile Cone, offshore Egypt, of which the dimensions and stratigraphic characteristics of a sub-set of 86 depletion zones associated with mud volcanoes of early Pliocene to Recent age are recorded. The primary database used is a large (4,300 km2) 3D seismic survey in which depletion zones can be confidently interpreted using a set of simple criteria. The sub-set of 86 depletion zones were selected for morphometric analysis by virtue of the quality of seismic imaging. The depletion zones are characterised by circular to elliptical planforms with a bowl or conical geometry. They exhibit truncational stratal relationships with their parent stratigraphic unit, which in this area is the Mid-Late Miocene aged OM2 unit, and which occurs directly beneath the Messinian Evaporites. This geometry implies a top-down formation mechanism. Their diameters and relief range from is 600 m–3300 m, and 100 m–740 m, respectively, with a modest scaling relationship between diameter and relief. Flank angles of bowls and cones range from 11⁰ to 41⁰, with a crudely normal distribution, with median and mean values of 26⁰. A model for the evolution of depletion zones in the study area is based on two previous models developed for single source layer plumbing systems and invokes mobilisation of the source layer by sediment collapse and shear-induced liquefaction following initial seal failure by hydraulic fracturing of the evaporite seal. This mechanism may be more widely applicable to mud volcano systems than currently appreciated

A Critical Tryptophan and Ca2+ in Activation and Catalysis of TPPI, the Enzyme Deficient in Classic Late-Infantile Neuronal Ceroid Lipofuscinosis

Tripeptidyl aminopeptidase I (TPPI) is a crucial lysosomal enzyme that is deficient in the fatal neurodegenerative disorder called classic late-infantile neuronal ceroid lipofuscinosis (LINCL). It is involved in the catabolism of proteins in the lysosomes. Recent X-ray crystallographic studies have provided insights into the structural/functional aspects of TPPI catalysis, and indicated presence of an octahedrally coordinated Ca(2+).Purified precursor and mature TPPI were used to study inhibition by NBS and EDTA using biochemical and immunological approaches. Site-directed mutagenesis with confocal imaging technique identified a critical W residue in TPPI activity, and the processing of precursor into mature enzyme.NBS is a potent inhibitor of the purified TPPI. In mammalian TPPI, W542 is critical for tripeptidyl peptidase activity as well as autocatalysis. Transfection studies have indicated that mutants of the TPPI that harbor residues other than W at position 542 have delayed processing, and are retained in the ER rather than transported to lysosomes. EDTA inhibits the autocatalytic processing of the precursor TPPI.We propose that W542 and Ca(2+) are critical for maintaining the proper tertiary structure of the precursor proprotein as well as the mature TPPI. Additionally, Ca(2+) is necessary for the autocatalytic processing of the precursor protein into the mature TPPI. We have identified NBS as a potent TPPI inhibitor, which led in delineating a critical role for W542 residue. Studies with such compounds will prove valuable in identifying the critical residues in the TPPI catalysis and its structure-function analysis

A systematic review of the diagnostic accuracy of physical examination for the detection of cirrhosis

BACKGROUND: We conducted a review of the diagnostic accuracy of clinical examination for the diagnosis of cirrhosis. The objectives were: to identify studies assessing the accuracy of clinical examination in the detection of cirrhosis; to summarize the diagnostic accuracy of reported physical examination findings; and to define the effects of study characteristics on estimates of diagnostic accuracy. METHODS: Studies were identified through electronic literature search of MEDLINE (1966 to 2000), search of bibliographic references, and contact with authors. Studies that evaluated indicants from physical examination of patients with known or suspected liver disease undergoing liver biopsy were included. Qualitative data on study characteristics were extracted. Two-by-two tables of presence or absence of physical findings for patients with and without cirrhosis were created from study data. Data for physical findings reported in each study were combined using Summary Receiver Operating Characteristic (SROC) curves or random effects modeling, as appropriate. RESULTS: Twelve studies met inclusion criteria, including a total of 1895 patients, ranging in age from 3 to 90 years. Most studies were conducted in referral populations with elevated aminotransferase levels. Ten physical signs were reported in three or more studies and ten signs in only a single study. Signs for which there was more study data were associated with high specificity (range 75–98%), but low sensitivity (range 15–68%) for histologically-proven cirrhosis. CONCLUSIONS: Physical findings are generally of low sensitivity for the diagnosis of cirrhosis, and signs with higher specificity represent decompensated disease. Most studies have been undertaken in highly selected populations