Has the mechanism by which the endocrine placenta scavenges the mother whilst sparing the foetus been unmasked?

The endocrine placenta has a dilemma; it shares the foetal circulation and yet it needs to secrete active peptide hormones into the maternal circulation to control her metabolism to meet the demands of the growing foetus. Simultaneously, it needs to allow the endocrine systems of the foetus to develop independently. This article will describe how peptide hormones are processed from inactive intermediates and will propose a hypothesis of how the placenta has revised this process to protect the foetus from the potentially damaging affects of these products.

Global iron-dependent gene regulation in Escherichia coli - A new mechanism for iron homeostasis

Organisms generally respond to iron deficiency by increasing their capacity to take up iron and by consuming intracellular iron stores. Escherichia coli, in which iron metabolism is particularly well understood, contains at least 7 iron-acquisition systems encoded by 35 iron-repressed genes. This Fe-dependent repression is mediated by a transcriptional repressor, Fur ( ferric uptake regulation), which also controls genes involved in other processes such as iron storage, the Tricarboxylic Acid Cycle, pathogenicity, and redox-stress resistance. Our macroarray-based global analysis of iron- and Fur-dependent gene expression in E. coli has revealed several novel Fur-repressed genes likely to specify at least three additional iron- transport pathways. Interestingly, a large group of energy metabolism genes was found to be iron and Fur induced. Many of these genes encode iron- rich respiratory complexes. This iron- and Fur-dependent regulation appears to represent a novel iron-homeostatic mechanism whereby the synthesis of many iron- containing proteins is repressed under iron- restricted conditions. This mechanism thus accounts for the low iron contents of fur mutants and explains how E. coli can modulate its iron requirements. Analysis of Fe-55-labeled E. coli proteins revealed a marked decrease in iron- protein composition for the fur mutant, and visible and EPR spectroscopy showed major reductions in cytochrome b and d levels, and in iron- sulfur cluster contents for the chelator-treated wild-type and/or fur mutant, correlating well with the array and quantitative RT-PCR data. In combination, the results provide compelling evidence for the regulation of intracellular iron consumption by the Fe2+-Fur complex.

Direct time-resolved study of the gas-phase reactions of germylene with ethyl- and diethylgermane: absolute rate constants, temperature dependences, and mechanism

Time-resolved studies of germylene, GeH2, generated by the 193 nm laser flash photolysis of 3,4-dimethyl-1-germacyclopent-3-ene, have been carried out to obtain rate constants for its bimolecular reactions with ethyl- and diethylgermanes in the gas phase. The reactions were studied over the pressure range 1-100 Torr with SF6 as bath gas and at five temperatures in the range 297-564 K. Only slight pressure dependences were found for GeH2 + EtGeH3 (399, 486, and 564 K). The high pressure rate constants gave the following Arrhenius parameters: for GeH2 + EtGeH3, log A = -10.75 +/- 0.08 and E-a = -6.7 +/- 0.6 kJ mol(-1); for GeH2 + Et2GeH2, log A = -10.68 +/- 0.11 and E-a = -6.95 +/- 0.80 kJ mol(-1). These are consistent with fast, near collision-controlled, association processes at 298 K. RRKM modeling calculations are, for the most part, consistent with the observed pressure dependence of GeH2 + EtGeH3. The ethyl substituent effects have been extracted from these results and are much larger than the analogous methyl substituent effects in the SiH2 + methylsilane reaction series. This is consistent with a mechanistic model for Ge-H insertion in which the intermediate complex has a sizable secondary barrier to rearrangement.

First crystallographic signature of an acyclic peptide nanorod: molecular mechanism of nanorod formation by a self-assembled tetrapeptide

A terminally protected acyclic tetrapeptide Boc-Aib-Val-Aib-beta-Ala-OMe 1 (Aib: alpha-aminoisobutyric acid, beta-Ala: beta-Alanine) self-assembles into a continuous hydrogen-bonded supramolecular helix with an average diameter of 10Angstrom (1nm) starting from a double bend molecular conformation in crystals and further self-assembly of this supramolecular architecture leads to the formation of polydisperse nanorods of diameters 10-40 nm.

Modelling metal cutting using modern ductile fracture mechanics: Quantitative explanations for some longstanding problems

The assumption that negligible work is involved in the formation of new surfaces in the machining of ductile metals, is re-examined in the light of both current Finite Element Method (FEM) simulations of cutting and modern ductile fracture mechanics. The work associated with separation criteria in FEM models is shown to be in the kJ/m2 range rather than the few J/m2 of the surface energy (surface tension) employed by Shaw in his pioneering study of 1954 following which consideration of surface work has been omitted from analyses of metal cutting. The much greater values of surface specific work are not surprising in terms of ductile fracture mechanics where kJ/m2 values of fracture toughness are typical of the ductile metals involved in machining studies. This paper shows that when even the simple Ernst–Merchant analysis is generalised to include significant surface work, many of the experimental observations for which traditional ‘plasticity and friction only’ analyses seem to have no quantitative explanation, are now given meaning. In particular, the primary shear plane angle φ becomes material-dependent. The experimental increase of φ up to a saturated level, as the uncut chip thickness is increased, is predicted. The positive intercepts found in plots of cutting force vs. depth of cut, and in plots of force resolved along the primary shear plane vs. area of shear plane, are shown to be measures of the specific surface work. It is demonstrated that neglect of these intercepts in cutting analyses is the reason why anomalously high values of shear yield stress are derived at those very small uncut chip thicknesses at which the so-called size effect becomes evident. The material toughness/strength ratio, combined with the depth of cut to form a non-dimensional parameter, is shown to control ductile cutting mechanics. The toughness/strength ratio of a given material will change with rate, temperature, and thermomechanical treatment and the influence of such changes, together with changes in depth of cut, on the character of machining is discussed. Strength or hardness alone is insufficient to describe machining. The failure of the Ernst–Merchant theory seems less to do with problems of uniqueness and the validity of minimum work, and more to do with the problem not being properly posed. The new analysis compares favourably and consistently with the wide body of experimental results available in the literature. Why considerable progress in the understanding of metal cutting has been achieved without reference to significant surface work is also discussed.

Fracture toughness and cutting

An exploratory model for cutting is presented which incorporates fracture toughness as well as the commonly considered effects of plasticity and friction. The periodic load fluctuations Been in cutting force dynamometer tests are predicted, and considerations of chatter and surface finish follow. A non-dimensional group is put forward to classify different regimes of material response to machining. It leads to tentative explanations for the difficulties of cutting materials such as ceramics and brittlo polymers, and also relates to the formation of discontinuous chips. Experiments on a range of solids with widely varying toughness/strength ratios generally agree with the analysis.

Toughness & cutting: A new way of determining ductile fracture toughness and strength

A review is given of the mechanics of cutting, ranging from the slicing of thin floppy offcuts (where there is negligible elasticity and no permanent deformation of the offcut) to the machining of ductile metals (where there is severe permanent distortion of the offcut/chip). Materials scientists employ the former conditions to determine the fracture toughness of ‘soft’ solids such as biological materials and foodstuffs. In contrast, traditional analyses of metalcutting are based on plasticity and friction only, and do not incorporate toughness. The machining theories are inadequate in a number of ways but a recent paper has shown that when ductile work of fracture is included many, if not all, of the shortcomings are removed. Support for the new analysis is given by examination of FEM simulations of metalcutting which reveal that a ‘separation criterion’ has to be employed at the tool tip. Some consideration shows that the separation criteria are versions of void-initiation-growth-and-coalescence models employed in ductile fracture mechanics. The new analysis shows that cutting forces for ductile materials depend upon the fracture toughness as well as plasticity and friction, and reveals a simple way of determining both toughness and flow stress from cutting experiments. Examples are given for a wide range of materials including metals, polymers and wood, and comparison is made with the same properties independently determined using conventional testpieces. Because cutting can be steady state, a new way is presented for simultaneously measuring toughness and flow stress at controlled speeds and strain rates.

Measuring toughness and the cohesive stress-displacement relationship by the essential work of fracture concept

The complete fracture behaviour of ductile double edge notched tension (DENT) specimen is analysed with an approximate model, which is then used to discuss the essential work of fracture (EWF) concept. The model results are compared with the experimental results for an aluminium alloy 6082-O. The restrictions on the ligament size for valid application of the EWF method are discussed with the aid of the model. The model is used to suggest an improved method of obtaining the cohesive stress-displacement relationship for the fracture process zone (FPZ).

Mode I fracture of sheet metal

The perceived wisdom about thin sheet fracture is that (i) the crack propagates under mixed mode I & III giving rise to a slant through-thickness fracture profile and (ii) the fracture toughness remains constant at low thickness and eventually decreases with increasing thickness. In the present study, fracture tests performed on thin DENT plates of various thicknesses made of stainless steel, mild steel, 6082-O and NS4 aluminium alloys, brass, bronze, lead, and zinc systematically exhibit (i) mode I “bath-tub”, i.e. “cup & cup”, fracture profiles with limited shear lips and significant localized necking (more than 50% thickness reduction), (ii) a fracture toughness that linearly increases with increasing thickness (in the range of 0.5–5 mm). The different contributions to the work expended during fracture of these materials are separated based on dimensional considerations. The paper emphasises the two parts of the work spent in the fracture process zone: the necking work and the “fracture” work. Experiments show that, as expected, the work of necking per unit area linearly increases with thickness. For a typical thickness of 1 mm, both fracture and necking contributions have the same order of magnitude in most of the metals investigated. A model is developed in order to independently evaluate the work of necking, which successfully predicts the experimental values. Furthermore, it enables the fracture energy to be derived from tests performed with only one specimen thickness. In a second modelling step, the work of fracture is computed using an enhanced void growth model valid in the quasi plane stress regime. The fracture energy varies linearly with the yield stress and void spacing and is a strong function of the hardening exponent and initial void volume fraction. The coupling of the two models allows the relative contributions of necking versus fracture to be quantified with respect to (i) the two length scales involved in this problem, i.e. the void spacing and the plate thickness, and (ii) the flow properties of the material. Each term can dominate depending on the properties of the material which explains the different behaviours reported in the literature about thin plate fracture toughness and its dependence with thickness.

Investigation of the fracture mode for hard and soft wheat endosperm using the loading-unloading bending test

Investigation of the fracture mode for hard and soft wheat endosperm was aimed at gaining a better understanding of the fragmentation process. Fracture mechanical characterization was based on the three-point bending test which enables stable crack propagation to take place in small rectangular pieces of wheat endosperm. The crack length can be measured in situ by using an optical microscope with light illumination from the side of the specimen or from the back of the specimen. Two new techniques were developed and used to estimate the fracture toughness of wheat endosperm, a geometric approach and a compliance method. The geometric approach gave average fracture toughness values of 53.10 and 27.0 J m(-2) for hard and soft endosperm, respectively. Fracture toughness estimated using the compliance method gave values of 49.9 and 29.7 J m(-2) for hard and soft endosperm, respectively. Compressive properties of the endosperm in three mutually perpendicular axes revealed that the hard and soft endosperms are isotropic composites. Scanning electron microscopy (SEM) observation of the fracture surfaces and the energy-time curves of loading-unloading cycles revealed that there was a plastic flow during crack propagation for both the hard and soft endosperms, and confirmed that the fracture mode is significantly related to the adhesion level between starch granules and the protein matrix.

Rate-dependent fracture toughness of polycrystalline ice

A series of three-point bend tests using single edge notched testpieces of pure polycrystalline ice have been performed at three different temperatures (–20°C, –30°C and –40°C). The displacement rate was varied from 1 mm/min to 100 mm/min, producing the crack tip strain rates from about 10–3 to 10–1 s–1. The results show that (a) the fracture toughness of pure polycrystalline ice given by the critical stress intensity factor (K IC) is much lower than that measured from the J—integral under identical conditions; (b) from the determination of K IC, the fracture toughness of pure polycrystalline ice decreases with increasing strain rate and there is good power law relationship between them; (c) from the measurement of the J—integral, a different tendency was appeared: when the crack tip strain rate exceeds a critical value of 6 × 10–3 s–1, the fracture toughness is almost constant but when the crack tip strain rate is less than this value, the fracture toughness increases with decreasing crack tip strain rate. Re-examination of the mechanisms of rate-dependent fracture toughness of pure polycrystalline ice shows that the effect of strain rate is related not only to the blunting of crack tips due to plasticity, creep and stress relaxation but also to the nucleation and growth of microcracks in the specimen.

An insight into the mechanism of protein separation by colloidal gas aphrons (CGA) generated from ionic surfactants

Colloidal gas aphrons (CGA), which are surfactant stabilised microbubbles, have been previously applied for the recovery of proteins from model mixtures and a few studies have demonstrated the potential of these dispersions for the selective recovery of proteins from complex mixtures. However there is a lack of understanding of the mechanism of separation and forces governing the selectivity of the separation. In this paper a mechanistic study is carried out to determine the main factors and forces influencing the selectivity of separation of whey proteins with CGA generated from ionic surfactants. Two different separation strategies were followed: (i) separation of lactoferrin and lactoperoxidase by anionic CGA generated from a solution of sodium bis-(2-ethyl hexyl) sulfosuccinate (AOT); (ii) separation of beta-lactoglobulin by cationic CGA generated from a solution of cetyltrimethylammonium bromide (CTAB). Separation results indicate that electrostatic interactions are the main forces determining the selectivity however these could not completely explain the selectivities obtained following both strategies. Protein-surfactant interactions were studied by measuring the zeta potential changes on individual proteins upon addition of surfactant and at varying pH. Interestingly strongest electrostatic interactions were measured at those pH and surfactant to protein mass ratios which were optimum for protein separation. Effect of surfactant on protein conformation was determined by measuring the change in fluorescence intensity upon addition of surfactant at varying pH. Differences in the fluorescence patterns were detected among proteins which were correlated to differences in their conformational features which could in turn explain their different separation behaviour. The effect of conformation on selectivity was further proven by experiments in which conformational changes were induced by pre-treatment of whey (heating) and by storage at 4 degrees C. Overall it can be concluded that separation of proteins by ionic CGA is driven mainly by electrostatic interactions however conformational features will finally determine the selectivity of the separation with competitive adsorption having also an effect. (c) 2006 Elsevier B.V. All rights reserved.

Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia

Aims/hypothesis Recent evidence suggests that a particular gut microbial community may favour occurrence of the metabolic diseases. Recently, we reported that high-fat (HF) feeding was associated with higher endotoxaemia and lower Bifidobacterium species (spp.) caecal content in mice. We therefore tested whether restoration of the quantity of caecal Bifidobacterium spp. could modulate metabolic endotoxaemia, the inflammatory tone and the development of diabetes. Methods Since bifidobacteria have been reported to reduce intestinal endotoxin levels and improve mucosal barrier function, we specifically increased the gut bifidobacterial content of HF-diet-fed mice through the use of a prebiotic (oligofructose [OFS]). Results Compared with normal chow-fed control mice, HF feeding significantly reduced intestinal Gram-negative and Gram-positive bacteria including levels of bifidobacteria, a dominant member of the intestinal microbiota, which is seen as physiologically positive. As expected, HF-OFS-fed mice had totally restored quantities of bifidobacteria. HF-feeding significantly increased endotoxaemia, which was normalised to control levels in HF-OFS-treated mice. Multiple-correlation analyses showed that endotoxaemia significantly and negatively correlated with Bifidobacterium spp., but no relationship was seen between endotoxaemia and any other bacterial group. Finally, in HF-OFS-treated-mice, Bifidobacterium spp. significantly and positively correlated with improved glucose tolerance, glucose-induced insulin secretion and normalised inflammatory tone (decreased endotoxaemia, plasma and adipose tissue proinflammatory cytokines). Conclusions/interpretation Together, these findings suggest that the gut microbiota contribute towards the pathophysiological regulation of endotoxaemia and set the tone of inflammation for occurrence of diabetes and/or obesity. Thus, it would be useful to develop specific strategies for modifying gut microbiota in favour of bifidobacteria to prevent the deleterious effect of HF-diet-induced metabolic diseases.