Development of feature detectors by self-organization

We present a two-layered network of linear neurons that organizes itself as to extract the complete information contained in a set of presented patterns. The weights between layers obey a Hebbian rule. We propose a local anti-Hebbian rule for lateral, hierarchically organized weights within the output layer. This rule forces the activities of the output units to become uncorrelated and the lateral weights to vanish. The weights between layers converge to the eigenvectors of the covariance matrix of input patterns, i.e., the network performs a principal component analysis, yielding all principal components. As a consequence of the proposed learning scheme, the output units become detectors of orthogonal features, similar to ones found in the brain of mammals.     

Can normal mode analysis reveal the geometry of the L550 chromophore of bacteriorhodopsin?

We discuss to what extent recent vibrational spectra of 14-²H, 15-²H and 14,15-²H isotopically labelled L₅₅₀ provide evidence for the occurrence of 13-cis, 14-s-trans or 13-cis, 14-s-cis chromophore structures in bacteriorhodopsin's photocycle. The discussion is based on a quantum chemical (MNDO) vibrational analysis of four molecular fragments as models for the retinal chromophore in bacteriorhodopsin.     

Intramitochondrial localization of δ-aminolaevulate synthetase and ferrochelatase in rat liver

Intramitochondrial loci for delta-aminolaevulate synthetase and ferrochelatase, the initial and final enzymes in haem synthesis, have been found in rat liver. Two different methods of fractionation were applied to mitochondria: (a) sonication and density-gradient centrifugation; (b) treatment with digitonin and differential centrifugation. Similar results were obtained with each technique. delta-Aminolaevulate synthetase is distributed similarly to two known matrix enzymes, malate dehydrogenase and glutamate dehydrogenase. Ferrochelatase is firmly bound to the the inner mitochondrial membrane. These results are considered in terms of the regulation of haem synthesis and in relation to mitochondrial biogenesis.     

Protein-Induced Membrane Curvature Investigated through Molecular Dynamics Flexible Fitting

In the photosynthetic purple bacterium Rhodobacter (Rba.) sphaeroides, light is absorbed by membrane-bound light-harvesting (LH) proteins LH1 and LH2. LH1 directly surrounds the reaction center (RC) and, together with PufX, forms a dimeric (RC-LH1-PufX)₂ protein complex. In LH2-deficient Rba. sphaeroides mutants, RC-LH1-PufX dimers aggregate into tubular vesicles with a radius of ∼250-550 Å, making RC-LH1-PufX one of the few integral membrane proteins known to actively induce membrane curvature. Recently, a three-dimensional electron microscopy density map showed that the Rba. sphaeroides RC-LH1-PufX dimer exhibits a prominent bend at its dimerizing interface. To investigate the curvature properties of this highly bent protein, we employed molecular dynamics simulations to fit an all-atom structural model of the RC-LH1-PufX dimer within the electron microscopy density map. The simulations reveal how the dimer produces a membrane with high local curvature, even though the location of PufX cannot yet be determined uniquely. The resulting membrane curvature agrees well with the size of RC-LH1-PufX tubular vesicles, and demonstrates how the local curvature properties of the RC-LH1-PufX dimer propagate to form the observed long-range organization of the Rba. sphaeroides tubular vesicles.     

Probing the role of structural water in a duplex oligodeoxyribonucleotide containing a water-mimicking base analog.

Molecular dynamics simulations were performed on models of the dodecamer DNA double-stranded segment, [d(CGCGAATTCGCG)](2), in which each of the adenine residues, individually or jointly, was replaced by the water-mimicking analog 2'-deoxy-7-(hydroxy-methyl)-7-deazaadenosine (hm(7)c(7)dA) [Rockhill, J.K., Wilson,S.R. and Gumport,R.I. (1996) J. Am. Chem. Soc.,118, 10065-10068]. The simulations, when compared with those of the dodecamer itself, show that incorporation of the analog affects neither the overall DNA structure nor its hydrogen-bonding and stacking interactions when it replaces a single individual base. Furthermore, the water molecules near the bases in the singly-substituted oligonucleotides are similarly unaffected. Double substitutions lead to differences in all the aforementioned parameters with respect to the reference sequence. The results suggest that the analog provides a good mimic of specific 'ordered' water molecules observed in contact with DNA itself and at the interface between protein and DNA in specific complexes.     

A structural model for force regulated integrin binding to fibronectin's RGD-synergy site.

The synergy site on fibronectin's FN-III(9) module, located approximately 32 A away from the RGD-loop on FN-III(10), greatly enhances integrin alpha(5)beta(1) mediated cell binding. Since fibronectin is exposed to mechanical forces acting on the extracellular matrix in vivo, we used steered molecular dynamics to study how mechanical stretching of FN-III(9-10) affects the relative distance between these two synergistic sites. Our simulations predict the existence of an intermediate state prior to unfolding. In this state, the synergy-RGD distance is increased from 32 A to approximately 55 A, while the conformations of both sites remain unperturbed. This distance is too large for both sites to co-bind the same receptor, as indicated by experiments that confirm that increasing the length of the linker chain between FN-III(9) and FN-III(10) reduces alpha(5)beta(1) binding. Our simulations thus suggest that increased alpha(5)beta(1)-binding attributed to the synergy site, along with the associated downstream cell-signaling events, can be turned off mechanically by stretching FN-III(9-10) into this intermediate state. The potential physiological implications are discussed.     

Determination of lithium and rubidium in physiological fluids and tissues of rabbits during the reproductive phase

1. The natural concentrations of lithium and rubidium were determined during the reproductive phase of rabbits by field desorption mass spectrometry. 2. Samples of serum, milk, amniotic fluid and placenta tissue were analysed. 3. The concentration changes in serum during the reproductive phase were between 2.61 and 5.02 micrograms/l for lithium and between 107.78 and 136.28 micrograms/l for rubidium. 4. Correlations between the concentration in maternal serum and bone growth of the fetus as well as the formation of milk were found. 5. Concentrations of 9.30 micrograms/l lithium and 1780.00 micrograms/l rubidium in the milk lead to the assumption that these trace metals are essential for the metabolism of the young rabbit.