A novel ras-related gene family

We have identified a new family of ras genes, the rho genes, which share several properties with the more classical ras gene family consisting of N-, K-, and H-ras. The rho genes, first isolated from a cDNA library from the abdominal ganglia of Aplysia, encode proteins that share 35% amino acid homology with H-ras. Evolutionarily conserved counterparts of rho have been detected in yeast, in Drosophila, in rat, and in man. Sequence analysis reveals over 85% homology between the human and Aplysia proteins. The ras and rho gene products share several common properties; both are 21,000 daltons, both reveal C-terminal sequences required for membrane attachment, and both show blocks of strong internal homology, suggesting that the two proteins may share common functions but may use these functions in different ways.     

Phylogeography,colonization and population history of the Midas cichlid species complex (<Emphasis Type="Italic">Amphilophus</Emphasis> spp.) in the Nicaraguan crater lakes

Background  

Elucidation of the mechanisms driving speciation requires detailed knowledge about the phylogenetic relationships and phylogeography of the incipient species within their entire ranges as well as their colonization history. The Midas cichlid species complex Amphilophus spp. has been proven to be a powerful model system for the study of ecological specialization, sexual selection and the mechanisms of sympatric speciation. Here we present a comprehensive and integrative phylogeographic analysis of the complete Midas Cichlid species complex in Nicaragua (> 2000 individuals) covering the entire distributional range, using two types of molecular markers (the mitochondrial DNA control region and 15 microsatellites). We investigated the majority of known lake populations of this species complex and reconstructed their colonization history in order to distinguish between alternative speciation scenarios.     

An Experimental and Theoretical Study on the Novel Tetraphosphorus Triselenide Boron Triiodide (P<Subscript>4</Subscript>Se<Subscript>3</Subscript>)·(BI<Subscript>3</Subscript>) Adduct

Tetraphosphorus triselenide boron triiodide (P₄Se₃)·(BI₃) has been prepared. The product formed has been characterized by Raman and IR spectroscopy. Vibrational assignments for the normal modes of this Lewis acid-base adduct have been made on the basis of comparison between theoretically obtained and experimentally observed Raman and IR data. The geometries of several possible tetraphosphorus triselenide boron triiodide (P₄Se₃)·(BI₃) adducts have been calculated. The bonding and electron transfer from the tetraphosphorus triselenide P₄Se₃ unit to the Lewis acid BI₃ has been investigated by applying NBO analysis.     

Integrating Dimension Reduction and Out-of-Sample Extension in Automated Classification of Ex Vivo Human Patellar Cartilage on Phase Contrast X-Ray Computed Tomography

Phase contrast X-ray computed tomography (PCI-CT) has been demonstrated as a novel imaging technique that can visualize human cartilage with high spatial resolution and soft tissue contrast. Different textural approaches have been previously investigated for characterizing chondrocyte organization on PCI-CT to enable classification of healthy and osteoarthritic cartilage. However, the large size of feature sets extracted in such studies motivates an investigation into algorithmic feature reduction for computing efficient feature representations without compromising their discriminatory power. For this purpose, geometrical feature sets derived from the scaling index method (SIM) were extracted from 1392 volumes of interest (VOI) annotated on PCI-CT images of ex vivo human patellar cartilage specimens. The extracted feature sets were subject to linear and non-linear dimension reduction techniques as well as feature selection based on evaluation of mutual information criteria. The reduced feature set was subsequently used in a machine learning task with support vector regression to classify VOIs as healthy or osteoarthritic; classification performance was evaluated using the area under the receiver-operating characteristic (ROC) curve (AUC). Our results show that the classification performance achieved by 9-D SIM-derived geometric feature sets (AUC: 0.96 ± 0.02) can be maintained with 2-D representations computed from both dimension reduction and feature selection (AUC values as high as 0.97 ± 0.02). Thus, such feature reduction techniques can offer a high degree of compaction to large feature sets extracted from PCI-CT images while maintaining their ability to characterize the underlying chondrocyte patterns.     

Integrating Protein Homeostasis Strategies in Prokaryotes

Bacterial cells are frequently exposed to dramatic fluctuations in their environment, which cause perturbation in protein homeostasis and lead to protein misfolding. Bacteria have therefore evolved powerful quality control networks consisting of chaperones and proteases that cooperate to monitor the folding states of proteins and to remove misfolded conformers through either refolding or degradation. The levels of the quality control components are adjusted to the folding state of the cellular proteome through the induction of compartment specific stress responses. In addition, the activities of several quality control components are directly controlled by these stresses, allowing for fast activation. Severe stress can, however, overcome the protective function of the proteostasis network leading to the formation of protein aggregates, which are sequestered at the cell poles. Protein aggregates are either solubilized by AAA+ chaperones or eliminated through cell division, allowing for the generation of damage-free daughter cells.     

Comparison of the structure of human recombinant short form stromelysin by multidimensional heteronuclear NMR and X-ray crystallography

Summary Stromelysin-1 is a matrix metalloprotease that has been implicated in a number of degenerative diseases. Here we present the refined NMR solution structure of the catalytic domain of stromelysin-1 complexed with a small inhibitor and compare it to the X-ray crystal structure of the same complex. The structures are similar in global fold and show an unusual bottomless S1' subsite. There are differences, however, in the least well defined regions, Phe⁸³-Ile⁸⁹, His²²⁴-Phe²³² and Pro²⁴⁹-Pro²⁵⁰, reflecting the lack of NOE data and large B-factors. The region His²²⁴-Phe²³² contains residues of the Sl' subsite and, consequently, small differences are observed in this subsite. Hydrogen-bond data show that, in contrast to the crystal structure, the solution structure lacks a hydrogen bond between the amide of Tyr²²³ and the carbonyl of the P3' residue. Analysis of bound water shows two tightly bound water molecules both in the solution and the crystal structure; neither of these waters are in the inhibitor binding site.Abbreviations MMP matrix metalloendoprotease - HMQC heteronuclear multiple quantum coherence - HSQC heteronuclear single quantum coherence - NOE nuclear Overhauser enhancement - NOESY NOE spectroscopy - PFG pulsed field gradient - sfSTR stromelysin-1 (EC 3.4.24.17), truncated at residue 255 The coordinates of the NMR solution structure (file name 2SRT) and the X-ray crystal structure (file name 1SLN) have been deposited in the Brookhaven Protein Data Bank.