Cardiac calcium currents at the level of single channels

Properties of cardiac Ca channels have come into sharper focus with the advent of single cell preparations and suction pipette recording methods. We briefly summarize our present picture of the gating and permeation properties of the conventional, dihydropyridine-sensitive type of Ca channel (L-type). Distinctive features of a second type of voltage-gated Ca channel (T-type) are discussed.     

Evidence for a constant number of available sweet receptor sites at threshold concentrations of sugars

Summary Intensity/time plots of sweetness produced by different molecules allow putative accession efficiencies of these molecules and their affinities with the taste receptor to be calculated. Results suggest that affinities of the different molecules are in the same order as threshold concentrations and that a constant number of available receptors exist for a related family of structures near threshold concentrations.     

Evidence for changes in cell shape from a 2-dimensional to a 3-dimensional substrate

Summary Chick embryo mesoderm cells were explanted to culture systems in vivo and in vitro and their subsequent movements were correlated with the external morphology as studied by SEM. In vitro cell movements are exaggerations of normal in vivo movements where a 2-dimensional substrate is encountered rather than a 3-dimensional environment.The authors are grateful to Mr J. Smith and Mrs S. Bulman who provided excellent technical assistance and to Mr G. L. C. McTurk who skillfully produced the scanning electron micrographs in the Leicester University Scanning Electron Microscope Unit.     

Nanoscale science: a big step towards the Holy Grail of single molecule biochemistry and molecular biology

Light scattering from metal nanoparticles and fluorescence from quantum dots offer distinct advantages over traditional fluorophores when it comes to detection of single molecules in living cells.Received 26 January 2004; received after revision 14 April 2004; accepted 23 April 2004     

Evidence for changes in cell shape from a 2-dimensional to a 3-dimensional substrate.

Chick embryo mesoderm cells were explanted to culture systems in vivo and in vitro and their subsequent movements were correlated with the external morphology as studied by SEM. In vitro cell movements are exaggerations of normal in vivo movements where a 2-dimensional substrate is encountered rather than a 3-dimensional environment.     

CD23 (the low-affinity IgE receptor) as a C-type lectin: a multidomain and multifunctional molecule

This review, regards the low-affinity receptor CD23 as a C-type lectin and compares it with other C-type lectins and C-type lectin-like receptors. C-type lectins such as the asialoglycoprotein receptor, as well as the dendritic cell immunoreceptor and the dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin on dendritic cell lectin, possess amino acid sequences which interact with Ca⁺⁺ and sugar, and many of them possess an endocytosis signal sequence that includes tyrosine or serine in the cytoplasmic region. In contrast, natural killer receptors lack the Ca⁺⁺ and sugar-binding amino acids but conserve homologous cysteines in the form of C-type lectin, and possess an immunoreceptor tyrosine-based inhibitory motif in the cytoplasmic region which inhibits killer activity when they recognize the self major histocompatibility (MHC) class I molecule. Since human CD23a form has a similar amino acid sequence, the possibility that this sequence is an endocytosis signal or an ITIM is discussed. The function of the reverse RGD and RGD-binding inhibitory peptide in human CD23 from the point of view of the relation between a C-type lectin and MHC class II molecules is also considered. Received 21 May 2001; received after revision 28 November 2001; accepted 29 November 2001     

Evidence that prokineticin receptor 2 exists as a dimer in vivo

Prokineticins are proteins that regulate diverse biological processes including gastrointestinal motility, angiogenesis, circadian rhythm, and innate immune response. Prokineticins bind two closed related G-protein coupled receptors (GPCRs), PKR1 and PKR2. In general, these receptors act as molecular switches to relay activation to heterotrimeric G-proteins and a growing body of evidence points to the fact that GPCRs exist as homo- or heterodimers. We show here by Western-blot analysis that PKR2 has a dimeric structure in neutrophils. By heterologous expression of PKR2 in Saccharomyces cerevisiae, we examined the mechanisms of intermolecular interaction of PKR2 dimerization. The potential involvement of three types of mechanisms was investigated: coiled-coil, disulfide bridges, and hydrophobic interactions between transmembrane domains. Characterization of differently deleted or site-directed PKR2 mutants suggests that dimerization proceeds through interactions between transmembrane domains. We demonstrate that co-expressing binding-deficient and signaling-deficient forms of PKR2 can re-establish receptor functionality, possibly through a domain-swapping mechanism.     

Photo- and heat-inactivation of taka-amylase a and substrate effects

Zusammenfassung Es werden die Bestimmung der thermodynamischen Quantitäten für die Inaktivierungsreaktionen, die Wärme- und Photo-Inaktivierungen der Taka-Amylase A und die Schutzwirkung des Substrats gegen diese Inaktivierungen diskutiert.     

A comparison of pyridoxal 5′-phosphate dependent decarboxylase and transaminase enzymes at a molecular level

Pyridoxal 5′-phosphate is a coenzyme for a number of enzymes which catalyse reactions at C^α of amino acid substrates including transaminases, decarboxylases and serine hydroxymethyltransferase. Using the X-ray coordinates for a transaminase, aspartate aminotransferase, and the results of stereochemical and mechanistic studies for decarboxylases and serine hydroxymethyltransferase, an active-site structure for the decarboxylase group is constructed. The structure of the active-site is further refined through active-site pyridoxyllysine peptide sequence comparison and a 3-D catalytic mechanism for the L-α-amino acid decarboxylases is proposed. The chemistry of serine hydroxymethyltransferase is re-examined in the light of the proposed decarboxylase mechanism.     

A comparison of pyridoxal 5'-phosphate dependent decarboxylase and transaminase enzymes at a molecular level.

Pyridoxal 5'-phosphate is a coenzyme for a number of enzymes which catalyse reactions at C alpha of amino acid substrates including transaminases, decarboxylases and serine hydroxymethyltransferase. Using the X-ray coordinates for a transaminase, aspartate aminotransferase, and the results of stereochemical and mechanistic studies for decarboxylases and serine hydroxymethyltransferase, an active-site structure for the decarboxylase group is constructed. The structure of the active-site is further refined through active-site pyridoxyllysine peptide sequence comparison and a 3-D catalytic mechanism for the L-alpha-amino acid decarboxylases is proposed. The chemistry of serine hydroxymethyltransferase is re-examined in the light of the proposed decarboxylase mechanism.     

Chromosomal organization at the level of gene complexes

Metazoan genomes primarily consist of non-coding DNA in comparison to coding regions. Non-coding fraction of the genome contains cis-regulatory elements, which ensure that the genetic code is read properly at the right time and space during development. Regulatory elements and their target genes define functional landscapes within the genome, and some developmentally important genes evolve by keeping the genes involved in specification of common organs/tissues in clusters and are termed gene complex. The clustering of genes involved in a common function may help in robust spatio-temporal gene expression. Gene complexes are often found to be evolutionarily conserved, and the classic example is the hox complex. The evolutionary constraints seen among gene complexes provide an ideal model system to understand cis and trans-regulation of gene function. This review will discuss the various characteristics of gene regulatory modules found within gene complexes and how they can be characterized.     

Consideration on the effects of pollution at community and population level

Summary The effects of pollution at population level are considered in relation to demographic characteristics and overall to the birthrate. The direct and indirect effects of pollution on community structure is discussed. The influence of pollution may vary according to the food-chain structure; (as a consequence, the hazard ceteris paribus will be greater in freshwater communities than in marine ones). Relations between diversity and stability are discussed. In addition, the advantages and difficulties in using diversity and biotic indices for monitoring polluted water are taken into account.     

The amylolysis of a substituted starch substrate

Zusammenfassung Bei Anwendung eines Stärkesubstrates in Verbindung mit einem im Kohlenstoffatom 6 kovalent gebundenen Farbstoffmolekül gelingt die differentielle Messung der - und -Amylase Aktivität im Reaktions-medium.     

Nonlinear identification of judgmental forecasts effects at SKU level

Prediction of demand is a key component within supply chain management. Improved accuracy in forecasts directly affects all levels of the supply chain, reducing stock costs and increasing customer satisfaction. In many application areas, demand prediction relies on statistical software which provides an initial forecast subsequently modified by the expert's judgment. This paper outlines a new methodology based on state‐dependent parameter (SDP) estimation techniques to identify the nonlinear behaviour of such managerial adjustments. This non‐parametric SDP estimate is used as a guideline to propose a nonlinear model that corrects the bias introduced by the managerial adjustments. One‐step‐ahead forecasts of stock‐keeping unit sales sampled monthly from a manufacturing company are utilized to test the proposed methodology. The results indicate that adjustments introduce a nonlinear pattern, undermining accuracy. This understanding can be used to enhance the design of the forecasting support system in order to help forecasters towards more efficient judgmental adjustments. Copyright © 2010 John Wiley & Sons, Ltd.     

LDL receptor relatives at the crossroad of endocytosis and signaling

For many years, the low-density lipoprotein (LDL) receptor and the LDL receptor-related protein (LRP) have been considered to be prototypes of cargo receptors which deliver, via endocytosis, macromolecules into cells. However, the recent identification of additional members of this gene family and examination of their biology has revealed that at least some of these proteins are also signaling receptors. Very low density lipoprotein receptor and ApoER2 transmit the extracellular reelin signal into migrating neurons, and thus are key components of the reelin pathway which governs neuronal layering of the forebrain during embryonic brain development. LRP5 and LRP6 are integral components of the Wnt signaling pathway which is central to many processes of metazoan development, cell proliferation, and tumor formation. Adaptor proteins interacting with the cytosolic domains of these receptors might orchestrate their ability to deliver their cargo or a signal.     

Consideration on the effects of pollution at community and population level.

The effects of pollution at population level are considered in relation to demographic characteristics and overall to the birthrate. The direct and indirect effects of pollution on community structure is discussed. The influence of pollution may vary according to the food-chain structure; (as a consequence, the hazard 'ceteris paribus' will be greater in freshwater communities than in marine ones). Relations between 'diversity' and 'stability' are discussed. In addition, the advantages and difficulties in using 'diversity' and 'biotic' indices for monitoring polluted water are taken into account.