A new principle for tight junction modulation based on occludin peptides

The aim of this study was to investigate whether peptides from the extracellular loops of the tight junction protein occludin could be used as a new principle for tight junction modulation. Peptides of 4 to 47 amino acids in length and covering the two extracellular loops of the tight junction protein occludin were synthesized, and their effect on the tight junction permeability in Caco-2 cells was investigated using [C-14] mannitol as a paracellular marker. Lipopeptide derivatives of one of the active occludin peptides (OPs), synthesized by adding a lipoamino acid containing 14 carbon atoms (C-14-) to the N terminus of the peptide, were also investigated. Peptides corresponding to the N terminus of the first extracellular loop of occludin increased the permeability of the tight junctions without causing short-term toxicity. However, the peptides had an effect only when added to the basolateral side of the cells, which could be partly explained by degradation by apical peptidases and aggregate formation. By contrast, the lipopeptide C-14-OP90-103, which protects the peptide from degradation and aggregation, displayed a rapid apical effect. The L- and D-diastereomers of C-14-OP90-103 had distinctly different effects. The D-isomer, which releases intact OP90-103 from the lipoamino acid, displayed a rapid and transient increase in tight junction permeability. The L- isomer, which releases OP90-103 more rapidly, gave a more sustained increase in tight junction permeability. In conclusion, C-14-OP90-103 represents a prototype of a new class of tight junction modulators that act on the extracellular domains of tight junction proteins.

The drying of sewage sludge by immersion frying

The objective of this work was to dry sewage sludge using a fry-drying process. The frying experiments were carried out in commercial fryers modified by adding thermocouples to the setup. During frying, typical drying curves were obtained and it was verified that, in relation to the parameters: oil temperature, oil type and shape of the sample, the shape factor the most effect on the drying rate, at least within the range chosen for the variables studied. Oil uptake and calorific value were also analyzed. The calorific value of the samples increased with frying time, reaching values around 24MJ/kg after 600s of frying (comparable to biocombustibles such as wood and sugarcane bagasse). The process of immersion frying showed great potential for drying materials, especially sewage sludge, obtaining a product with a high energy content, thereby increasing its value as a combustible.

Cyclopropane-1,1-dicarboxylate is a slow-, tight-binding inhibitor of rice ketol-acid reductoisomerase

Ketol-acid reductoisomerase (EC 1.1.1.86) catalyses the second reaction in the biosynthesis of the branched-chain amino acids. The reaction catalyzed consists of two stages, the first of which is an alkyl migration from one carbon atom to its neighbour. The likely transition state is therefore a cyclopropane derivative, and cyclopropane-1,1-dicarboxylate(CPD) has been reported to inhibit the Escherichia coli enzyme. In addition, this compound causes the accumulation of the substrate of ketol-acid reductoisomerase in plants. Here, we investigate the inhibition of the purified rice enzyme. The cDNA was cloned, and the recombinant protein was expressed in E. coli, purified and characterized kinetically. The purified enzyme is strongly inhibited by cyclopropane-1,1-dicarboxylate, with an inhibition constant of 90 nM. The inhibition is time-dependent and this is due to the low rate constants for formation (2.63 X 10(5) M-1 min(-1)) and dissociation (2.37 x 10(-2) min(-1)) of the enzyme-inhibitor complex. Other cyclopropane derivatives are much weaker inhibitors while dimethylmalonate is moderately effective. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

Family violence: Walking the tight rope between maternal alienation and child safety

Mothers are often alienated from their children when child abuse is suspected or confirmed, whether she is the primary abuser of the child or not. An abusive or violent partner often initiates the process of maternal alienation from children as a control mechanism. When the co-occurrence of maternal and child abuse is not recognised, nurses and health professionals risk further alienating a mother from her children, which can have detrimental effects in both the short and long term. Evidence shows that when mothers are supported and have the necessary resources there is a reduction in the violence and abuse she and her children experience; this occurs even in situations where the mother is the primary abuser of her children. The family-centred care philosophy, which is widely accepted as the best approach to nursing care for children and their families, creates tension for nurses caring for children who are the victims of abuse as this care generally occurs away from the context of the family. This fragmented approach to caring for abused children can inadvertently undermine the mother-child relationship and further contribute to maternal alienation. This paper discusses the complexity of family violence for nurses negotiating the 'tight rope' between the prime concern for the safety of children and further contributing to maternal alienation, within a New Zealand context. The premise that restoration of the mother-child relationship is paramount for the long-term wellbeing of both the children and the mother provides the basis for discussing implications for nursing practice.

Specific modulation of airway epithelial tight junctions by apical application of an occludin peptide

Tight junctions are directly involved in regulating the passage of ions and macromolecules (gate functions) in epithelial and endothelial cells. The modulation of these gate functions to transiently regulate the paracellular permeability of large solutes and ions could increase the delivery of pharmacological agents or gene transfer vectors. To reduce the inflammatory responses caused by tight junction-regulating agents, alternative strategies directly targeting specific tight junction proteins could prove to be less toxic to airway epithelia. The apical delivery of peptides corresponding to the first extracellular loop of occludin to transiently modulate apical paracellular flux has been demonstrated in intestinal epithelia. We hypothesized that apical application of these occludin peptides could similarly modulate tight junction permeability in airway epithelia. Thus, we investigated the effects of apically applied occludin peptide on the paracellular permeability of molecular tracers and viral vectors in well differentiated human airway epithelial cells. The effects of occludin peptide on cellular toxicity, tight junction protein expression and localization, and membrane integrity were also assessed. Our data showed that apically applied occludin peptide significantly reduced transepithelial resistance in airway epithelia and altered tight junction permeability in a concentration-dependent manner. These alterations enhanced the paracellular flux of dextrans as well as gene transfer vectors. The occludin peptide redistributed occludin but did not alter the expression or distribution of ZO-1, claudin-1, or claudin-4. These data suggest that specific targeting of occludin could be a better-suited alternative strategy for tight junction modulation in airway epithelial cells compared with current agents that modulate tight junctions.

Performance impact of asymmetric filtered 40Gb/s RZ DPSK system:tight optical filtering considerations

We present the impact of Asymmetric filtering of strong (e.g. 35 GHz) optical filters on the performance of 42.7 Gb/s 50% RZ-DPSK systems. The performance is evaluated when offsetting the filter by substantial amounts and it is found that with an offset of almost half the bit rate there is a significant improvement in the calculated Q.

Optical immersion of mid-infrared LEDs and photodiodes for gas-sensing applications

The high gains in performance predicted for optical immersion are difficult to achieve in practice due to total internal reflection at the lens/detector interface. By reducing the air gap at this interface optical tunneling becomes possible and the predicted gains can be realized in practical devices. Using this technique we have demonstrated large performance gains by optically immersing mid-infrared heterostructure InA1Sb LEDs and photodiodes using hypershperical germanium lenses. The development of an effective method of optical immersion that gives excellent optical coupling has produced a photodiode with a peak room temperature detectivity (D*) of 5.3 x 109 cmHz½W-1 at λpeak=5.4μm and a 40° field of view. A hyperspherically immersed LED showed a f-fold improvement in the external efficiency, and a 3-fold improvement in the directionality compared with a conventional planar LED for f/2 optical systems. The incorporation of these uncooled devices in a White cell produced a NO2 gas sensing system with 2 part-per-million sensitivity, with an LED drive current of <5mA. These results represent a significant advance in the use of solid state devices for portable gas sensing systems.

Lessons learned from the effect of tight monetary conditions and crises on corporate capital structure

The study reviews the theoretical and empirical literature on the effect of tight monetary conditions, crisis on corporate capital structure, further creates a framework for analyzing their relation, as well as sheds light on the lessons learned and open research areas. The results highlight that the supply side of capital has an effect on corporate capital structure, though the analysis of this relation is scarce. However, the impact of tight monetary conditions on capital structure is analyzed by several studies, there is limited evidence on the financial policy and the development of financing mix during a crisis period. The impact of the 2007/08 crisis on the corporate capital structure and especially in case of firms with impaired access to external financing is scarce. The study also highlights our lack in understanding of the relation of crisis and capital structure in case of the CEE region.