Menin, the product of the MEN1 gene, is a nuclear protein

The MEN1 gene, mutations in which are responsible for multiple endocrine neoplasia type 1 (MEN1), encodes a 610-amino acid protein, denoted menin. The amino acid sequence of this putative tumor suppressor offers no clue to the function or subcellular location of the protein. We report herein, based on immunofluorescence, Western blotting of subcellular fractions, and epitope tagging with enhanced green fluorescent protein, that menin is located primarily in the nucleus. Enhanced green fluorescent protein-tagged menin deletion constructs identify at least two independent nuclear localization signals (NLS), both located in the C-terminal fourth of the protein. Among the 68 known independent disease-associated mutations, none of the 22 missense and 3 in-frame deletions affect either of the putative NLS sequences. However, if expressed, none of the truncated menin proteins resulting from the 43 known frameshift/nonsense mutations would retain both the NLSs. The precise role(s) of menin in the nucleus remain to be understood.     

Subclinical surface alterations of human pleura. A scanning electron microscopic study

Pleuritis or pleural effusion frequently develops in patients with pneumonia or heart failure. Most of these pleural changes regress without intrapleural intervention. The detailed mechanisms of the regression of the pleural changes in humans are not well documented. We studied the parietal pleura of nine patients with lung cancer and two patients with coronary artery disease by scanning electron microscopy (SEM). All patients had neither radiographic nor gross evidence of pleural disease but all had mixed surface alterations by SEM. Focal denudation of mesothelial cells was common. Deeper injuries exposed thick and thin interweaving collagen bundles. Patchy depositions of amorphous or crystallized fibrin covered normal and damaged pleural surfaces, frequently admixed with macrophages, red blood cells, and tissue debris. Reactive mesothelial cells appeared to proliferate over the fibrin. Our findings suggest that subclinical pleural alterations occur often in patients with pulmonary or cardiac diseases and that an intact pleural surface in those patients is restored mainly by the proliferation of reactive mesothelial cells.     

The membrane-cytoplasm interface of integrin alpha subunits is critical for receptor latency

Localization of integrin receptors to focal contact sites occurs upon ligand binding. This activity is latent, since unoccupied integrin receptors do not localize to focal contacts. Deletion analysis has revealed that the alpha cytoplasmic domains is required for the maintenance of integrin receptor latency. Our current hypothesis for the mechanism of integrin post-ligand binding events is that there is a change in relationship of alpha and beta cytoplasmic domains, which overcomes receptor latency. One possible mechanism for such a change would involve the amino acid residues at the membrane-cytoplasm interface. To test this hypothesis, we have produced point mutations in the human integrin alpha 1 subunit. These mutations had no effect on the adhesion via alpha 1 beta 1 to its ligand, collagen IV. However, receptor latency is lost in one of these mutants, leading to constitutive focal contact localization. This effect did not occur in receptors with an exchange of intracellular domains, suggesting that the mechanism of loss of latency involves a relative motion of the integrin chains. These results suggest a model in which post-ligand binding events in integrin receptors are associated with changes in the position of the alpha and beta cytoplasmic domains.     

Signal Processing for Semiconductor Detectors

This is a tutorial paper designed to provide a balanced perspective on the processing of signals produced by semiconductor detectors. The general problems of pulse shaping to optimize resolution with constraints imposed by noise, counting rate and rise time fluctuations are discussed.     

Estimation of timber volume in a coniferous plantation forest using Landsat TM

Optimisation of economic return from forests requires that comprehensive forest inventory data be available to support the design of harvesting strategies. Such inventory data can potentially be obtained by remote sensing. This study investigates the accuracy with which wood volume (m3 ha -1) in a plantation forest can be calculated from Landsat TM data at the pixel and foreststand spatial scales. Wood volumes were estimated from regression analysis, nonparametric line-fitting, and an N-dimensional K-nearest-neighbour classification scheme. At the pixel scale, relations between Landsat data and measured wood volume were found to be significant but weak, with r2 values of 0.3, and with correspondingly poor estimates of wood volume (root-mean-square errors rmses of 100 m3 ha -1). By averaging the pixel-scale estimates, wood volume estimates of acceptable accuracy were obtained for forest-stand areas of about 40 ha (rmses of 46 m3 ha -1). Parametric regression performed slightly better overall than non-parametric line fitting techniques for estimating wood volume. Estimates of similar accuracy to those obtained by regression were also given by NK-classification at the pixel-scale, provided K was large ( 15), although the classifier produced biased results at the forest-stand scale. It is concluded that Landsat TM only provides an acceptable data source for estimating wood volumes in plantation forests for areas of about 40 ha and larger. The very low dynamic range in the Landsat data is probably a significant factor limiting its use for inventory at more detailed scales.     

Detailed active site configuration of a new crystal form of methanol dehydrogenase from Methylophilus W3A1 at 1.9 A resolution

The three-dimensional structure of a new crystal form of methanol dehydrogenase from Methylophilus W3A1 has been obtained in the presence of substrate using data recorded at a synchrotron. The structure of this approximately 140 kDa heterotetramer, refined at 1. 9 A resolution, reveals the detailed configuration of its redox cofactor, pyrroloquinoline quinone (PQQ). C4, one of the oxygen-bearing atoms of this orthoquinone is in a planar configuration while C5, which bears the other quinone oxygen, is tetrahedral, suggesting that the PQQ is in the semiquinone redox state. The substrate binding site has been identified close to PQQ and to the side chain of Asp297, the putative active site base. The proximity of the hydroxyl of methanol to C5 of PQQ compared to the greater separation of the substrate methyl group from C5 supports the addition-elimination reaction mechanism involving a hemiketal intermediate.     

Inhibition of proliferation and expression of T-antigen in SV40 large T-antigen gene-induced immortalized cells following transplantations

In this paper the Authors reviewed the recent literature for a more comprehensive and clear vision of the epidemiological and pathological aspects of retroperitoneal sarcomas. The most effective procedures for a an early and accurate diagnosis were identified. Moreover, the different therapeutic choices were taken into account focusing on those provided of the major potential in terms of oncologically valid treatment.