Confirmation of the structure of nisin and its major degradation product by FAB-MS and FAB-MS/MS

Summary FAB-MS has been applied to the analysis of a nisin complex and FAB-MS and FAB-MS/MS data from the major component used to provide confirmation of the amino sequence and positions of the sulphur-bridged rings in these highly modified peptides.     

Relevance of chlorine-substituent for the antifungal activity of syringomycin and syringotoxin,metabolites of the phytopathogenic bacteriumPseudomonas syringae pv.syringae

Structural analogues of syringomycin and syringotoxin were produced by fermentation, characterized by FAB-MS and amino acid analysis and compared to the parent compounds in the antibiosis test againstRhodotorula pilimanae. The C-terminal residue was shown to be important for the activity.     

Structuralism and the conformity of mathematics and nature

Structuralists typically appeal to some variant of the widely popular ‘mapping’ account of mathematical representation to suggest that mathematics is applied in modern science to represent the world’s physical structure. However, in this paper, I argue that this realist interpretation of the ‘mapping’ account presupposes that physical systems possess an ‘assumed structure’ that is at odds with modern physical theory. Through two detailed case studies concerning the use of the differential and variational calculus in modern dynamics, I show that the formal structure that we need to assume in order to apply the mapping account is inconsistent with the way in which mathematics is applied in modern physics. The problem is that a realist interpretation of the ‘mapping’ account imposes too severe of a constraint on the conformity that must exist between mathematics and nature in order for mathematics to represent the structure of a physical system.     

Mutagenicity and toxicity of chloroethylene oxide and chloroacetaldehyde

Summary Exposure of severaltrp-auxotrophicEscherichia coli strains, carrying base0pair substitutions, to chloroethylene oxide or chloroacetaldehyde (two metabolites of vinyl chloride) increased the mutation frequency to tryptophan prototrophy. Strong cytotoxic and mutagenic effects were observed with 2.5 mM chloroethylene oxide, while a higher concentration of chloroacetaldehyde (100 mM) exhibited a mutagenic effect which was 400 times lower.I am grateful to Prof. G. Michel, Laboratoire de Biochimie Microbienne, and to Dr H. Bartsch, International Agency for Research on Cancer, for the support of this work. I wish to thank Dr F. Besson-Simien and Dr A. Barbin for their collaboration.     

The metabolism and function of sphingolipids and glycosphingolipids

Sphingolipids and glycosphingolipids are emerging as major players in many facets of cell physiology and pathophysiology. We now present an overview of sphingolipid biochemistry and physiology, followed by a brief presentation of recent advances in translational research related to sphingolipids. In discussing sphingolipid biochemistry, we focus on the structure of sphingolipids, and their biosynthetic pathways – the recent identification of most of the enzymes in this pathway has led to significant advances and better characterization of a number of the biosynthetic steps, and the relationship between them. We then discuss some roles of sphingolipids in cell physiology, particularly those of ceramide and sphingosine-1-phosphate, and mention current views about how these lipids act in signal transduction pathways. We end with a discussion of sphingolipids and glycosphingolipids in the etiology and pathology of a number of diseases, such as cancer, immunity, cystic fibrosis, emphysema, diabetes, and sepsis, areas in which sphingolipids are beginning to take a central position, even though many of the details remain to be elucidated. Received 13 February 2007; received after revision 19 April 2007; accepted 26 April 2007     

Molecular and Cellular Basis of Regeneration and Tissue Repair

Planarians possess amazing abilities to regulate tissue homeostasis and regenerate missing body parts. These features reside on the presence of a population of pluripotent/totipotent stem cells, the neoblasts, which are considered as the only planarian cells able to proliferate in the asexual strains. Neoblast distribution has been identified by mapping the cells incorporating bromodeoxyuridine, analyzing mitotic figures and using cell proliferation markers. Recently identified molecular markers specifically label subgroups of neoblasts, revealing thus the heterogeneity of the planarian stem cell population. Therefore, the apparent totipotency of neoblasts probably reflects the composite activities of multiple stem cell types. First steps have been undertaken to understand how neoblasts and differentiated cells communicate with each other to adapt the self-renewal and differentiation rates of neoblasts to the demands of the body. Moreover, the introduction of molecular resource database on planarians now paves the way to renewed strategies to understand planarian regeneration and stem cell-related issues.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

Tissue repair and regeneration are very complex biological events, whose successful attainment requires far more than mere cell division. However, almost unavoidably they entail cell proliferation as a fundamental premise. Full regeneration or repair cannot be achieved without replacing cells lost to disease or injury, replacement that can only take place via proliferation of surviving cells. This review endeavors to outline the molecular bases of exit from and reentry into the cell cycle. In recent years, the decision to proliferate or not has been seen as mostly the concern of cyclins and cyclin-dependent kinases. This account tries to show that cell cycle inhibitors are as important as the positive regulators in the making of this decision. Finally, the authors wish to suggest that the molecular knowledge of the cell cycle can be harnessed to the benefit of many aspects of regenerative medicine.     

Properties and modes of action of specific and non-specific phospholipid transfer proteins

We have described the mode of action of the phosphatidylcholine transfer protein (PC-TP), the phosphatidylinositol transfer protein (PI-TP) and the non-specific lipid transfer protein (nsL-TP) isolated from bovine and rat tissues. PC-TP and PI-TP specifically bind one phospholipid molecule to be carried between membranes. PC-TP, and most likely PI-TP as well, have independent binding sites for the sn-1- and sn-2-fatty acyl chains. These sites have different properties, which may explain the ability of PC-TP and PI-TP to discriminate between positional phospholipid isomers. nsL-TP, which is identical to sterol carrier protein 2, transfers all common phospholipids, cholesterol and oxysterol derivatives between membranes. This protein is very efficient in mediating a net mass transfer of lipids to lipid-deficient membranes. Models for its mode of action, which is clearly different from that of PC-TP and PI-TP, are presented.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

The ability to produce differentiated cell types at will offers one approach to cell therapy and therefore the treatment and cure of degenerative diseases such as diabetes and liver failure. Until recently it was thought that differentiated cells could only be produced from embryonic or adult stem cells. However, we now know that this is not the case, and there is a growing body of evidence to show that one differentiated cell type can convert into a completely different phenotype (transdifferentiation). Understanding the cellular and molecular basis of transdifferentiation will allow us to reprogram cells for transplantation. This approach will complement the use of embryonic and adult stem cells in the treatment of degenerative disorders. In this review, we will focus on some well-documented examples of transdifferentiation.     

Starvation and penetration of bacteria in soils and rocks

Summary The soil and subsurface strata are low nutrient environments and their bacterial inhabitants must adopt starvation responses to survive. These responses include the formation of dormant, viable cells which, although reduced in cell size and volume, are able to respond to any improvement in nutrient availability. Starved bacteria are able to survive for extended periods without nutrients and their reduced size allows them to disperse deeply within rocks and soils greatly improving their penetration. These combined factors may increase opportunities for bacteria to reach a deep waste disposal site.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

Although early after birth the central nervous system is more plastic than in the adult, it already displays limited regenerative capability. This becomes severely impaired at specific stages of embryonic development; however, the precise cellular and molecular basis of this loss is not fully understood. The chick embryo provides an ideal model for direct comparisons of regenerating and non-regenerating spinal cord within the same species because of its accessibility in ovo, the extensive knowledge of chick neural development and the molecular tools now available. Regenerative ability in the chick is lost at around E13, a relatively advanced stage of spinal cord development. This is most likely due to a complex series of events: there is evidence to suggest that developmentally regulated changes in the early response to injury, expression of inhibitory molecules and neurogenesis may contribute to loss of regenerative capacity in the chick spinal cord.     

Properties and modes of action of specific and non-specific phospholipid transfer proteins

Summary We have described the mode of action of the phosphatidylcholine transfer protein (PC-TP), the phosphatidylinositol transfer protein (PI-TP) and the non-specific lipid transfer protein (nsL-TP) isolated from bovine and rat tissues. PC-TP and PI-TP specifically bind one phospholipid molecule to be carried between membranes. PC-TP, and most likely PI-TP as well, have independent binding sites for thesn-1- andsn-2-fatty acyl chains. These sites have different properties, which may explain the ability of PC-TP and PI-TP to discriminate between positional phospholipid isomers. nsL-TP, which is identical to sterol carrier protein 2, transfers all common phospholipids, cholesterol and oxysterol derivatives between membranes. This protein is very efficient in mediating a net mass transfer of lipids to lipid-deficient membranes. Models for its mode of action, which is clearly different from that of PC-TP and PI-TP, are presented.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

Cell plasticity and mesenchymal-epithelial interactions are regarded as a hallmark of embryonic development and are not believed to occur extensively in the adult. Recently, adult mesenchymal stem cells were reported to differentiate in culture into a variety of mature cell types, including epithelial cells. Progress in stem and progenitor cell biology and recognition of the unique properties of such cells may enable intelligent bioengineering design of replacement skin which allows regeneration to occur in vivo. Ideally, a scaffold-free environment which stimulates skin stem cells in situ to initiate cell signals that result in regeneration rather than scar formation is required. Various skin progenitor cell types are considered along with the signalling cascades that they affect. We also discuss a mammalian model of scar-free regeneration. Many of these mechanisms, if fully understood, could be harnessed after injury to perfectly restore the skin.     

Control of infection by pyroptosis and autophagy: role of TLR and NLR

Cells can die by distinct mechanisms with particular impacts on the immune response. In addition to apoptosis and necrosis, recent studies lead to characterization of a new pro-inflammatory form of cell death, pyroptosis. TLR and NLR, central innate immune sensors, can control infections by modulating host cell survival. In addition, TLRs can promote the induction of autophagy, thus promoting delivery of infecting pathogens to the lysosomes. On the other hand, activation of some NLR members, especially NLRC4 and NAIP5, leads to the infected cell death by pyroptosis, which is accompanied by secretion of the pro-inflammatory cytokines IL-1β, IL-18, and IL-33. Data presented here illustrate how the compartmentalization of the innate immune sensors can influence the outcome of infections by controlling the fate of host cells.     

Auditory and visual perception of simultaneous verbal and nonverbal stimuli

Summary In an auditory experiment, digits and tonal sequences were presented simultaneously to both ears. In a visual experiment, words and nonsense figures had to be compared in both visual half-fields. The verbal stimuli were better reported from the right ear and right visual half-field. The nonverbal stimuli were reported equally well from both ears and visual half-fields. It appears that the processing of stimuli presented to both input channels depends on the type of the stimuli. These results point to a cerebral mechanism classifying incoming information to the brain and yielding an optimal processing of verbal and nonverbal stimuli by the cerebral hemispheres.This study was supported in part by grants 6.182-0.76 and 6.183-0.76 of the Swiss National Science Foundation to E. Perret.     

The functioning and interrelationships of blood capillaries and lymphatics

Summary the structure and function of blood capillaries, as related to permeability, depends on tight, close and (in injured vessels) open junctional regions, small vesicles, vacuoles (in injured vessels) and fenestrae. The basement membrane presents a hindrance to the larger macromolecules, at high flow rates, but not to small molecules. The connective tissue channels are probably the paths by which macromolecules, and most of the small ones, pass from the arterial-limbs to the venous ones, and to the lymphatics. In some regions these channels are grouped in special systems: the prelymphatics. The initial lymphatics take up material via open junctions, which close during tissue-compression. The collecting lymphatics retain the lymph because they do not have open junctions.In the close junctional regions the motive force for water flow is the result of Starling's forces; diffusion is very important for other small molecules. The small vesicles transport macromolecules slowly by Brownian motion, as may the vacuoles, but possibly these latter are moved actively.There is much evidence that colloids can develop high effective osmotic pressures even across pores much larger than their molecules, and that proteins can be dragged up a concentration gradient by the resultant fluid flow. On the basis of this, hypotheses have been developed about the functioning of venous-limb fenestrae and the initial lymphatics, for which there is much theoretical, in vitro, and in vivo evidence. Thus, in fenestrae and regions there is held to be a large local circulation through the tissues, of which a quantitatively small, but qualitatively vital, part goes to the lymphatics. Material is considered usually to enter these latter because of the relative concentration of the lymph.It is becoming increasingly evident that in the study of the microvasculature, as with other systems, there is much to be gained by quantifying fine structural observations and by combining and contrasting this data, via physical laws, with that obtained by other methods where the characteristics of whole organs and regions are studied. Thus one can obtain interrelated information, which is not possible by either method alone, and which gives us a vital, comprehensive, perspective of the ways in which whole systems function, and how different systems interact. In this paper I shall show how this approach has yielded much that is new about the functioning of different kinds of blood capillaries, of the tissue channels, of the whole lymphatic system, and of the ways they affect each other.Most of the author's work reported here was financed by the Australian Research Grants Committee.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

The Xenopus tadpole is a favourable organism for regeneration research because it is suitable for a wide range of micromanipulative procedures and for a wide range of transgenic methods. Combination of these techniques enables genes to be activated or inhibited at specific times and in specific tissue types to a much higher degree than in any other organism capable of regeneration. Regenerating systems include the tail, the limb buds and the lens. The study of tail regeneration has shown that each tissue type supplies the cells for its own replacement: there is no detectable de-differentiation or metaplasia. Signalling systems needed for regeneration include the BMP and Notch signalling pathways, and perhaps also the Wnt and FGF pathways. The limb buds will regenerate completely at early stages, but not once they are fully differentiated. This provides a good opportunity to study the loss of regenerative ability using transgenic methods.     

Mutagenicity and toxicity of chloroethylene oxide and chloroacetaldehyde

Exposure of several trp-auxotrophic Escherichia coli strains, carrying base-pair substitutions, to chloroethylene oxide or chloroacetaldehyde (two metabolites of vinyl chloride) increased the mutation frequency to tryptophan prototrophy. Strong cytotoxic and mutagenic effects were observed with 2.5 mM chloroethylene oxide, while a higher concentration of chloroacetaldehyde (100 mM) exhibited a mutagenic effect which was 400 times lower.     

Ecological and evolutionary implications of digestive processes: Bird preferences and the sugar constituents of floral nectar and fruit pulp

Plants pollinated and dispersed by different groups of birds offer different kinds of sugars in nectar and fruit pulp. The preferences and physiological traits of avian pollinators and seed dispersers are broadly correlated with the sugar composition of the nectar and fruit that they feed on and appear to have influenced the evolution of the sugar composition of the rewards that plants offer. Hummingbirds prefer sucrose whereas many nectar- and fruit-eating passerines prefer glucose and fructose. Preference for hexoses in passerines seems to be associated with poor sucrose assimilation resulting from two physiological mechanisms: lack of intestinal sucrase activity and fast passage rates. Sucrase activity absence appears to be restricted to a single phylogenetic group (the sturnid-muscicapid lineage). Fast passage rates seem to be characteristic of many small frugivores and to hinder the assimilation of complex nutrients that require hydrolysis before absorption. Hummingbirds have extremely specialized digestive traits that allow them to assimilate sucrose at high rates and with extremely high efficiency. These specialized digestive traits appear not to be present in many nectar-feeding passerines.