Preservation of native conformation during aluminium-induced aggregation of tau protein

ALUMINIUM exposure has been shown to result in aggregation of microtubule-associated protein tau in vitro. In the light of recent observations that the native random structure of tau protein is maintained in its monomeric and dimeric states as well as in the paired helical filaments characteristic of Alzheimer's disease, it is likely that factors playing a causative role in neurofibrillary pathology would not drastically alter the native conformation of tau protein. We have studied the interaction of tau protein with aluminium using circular dichroism (CD) and 27(Al) NMR spectroscopy. The CD studies revealed a five-fold increase in the observed ellipticity of the tau-aluminium assembly. The increase in elipticity was not associated with a change in the general conformation of the protein and was most likely due to an aggregation of the tau protein induced by aluminium. Al-27 NMR spectroscopy confirmed the binding of aluminium to tau protein. Hyperphosphorylation of tau in Alzheimer's disease is known to be associated with defective microtubule assembly in this condition. Abnormally phosphorylated tau exists in a polymerized form in the paired helical filaments (PHF) which constitute the neurofibrillary tangles found in Alzheimer's disease. While it is hypothesized that its altered biophysical characteristics render abnormally phosphorylated tau resistant to proteolysis, causing the formation of stable deposits,the sequence of events resulting in the polymerization of tau are little understood, as are the additional factors or modifications required for tills process. Based on the results of our spectroscopic studies, a model for the sequence of events occurring in neurofibrillary pathology is proposed.

Extract from plants

An extract of organic material from a species selected from the tribe Nicotianeae that comprises a mixture of C26 to C33 alkanes at a purity of at least 90% by volume of total extract.

Tripogon loliiformis elicits a rapid physiological and structural response to dehydration for desiccation tolerance

Resurrection plants can withstand extreme dehydration to an air-dry state and then recover upon receiving water. Tripogon loliiformis (F.Muell.) C.E.Hubb. is a largely uncharacterised native Australian desiccation-tolerant grass that resurrects from the desiccated state within 72 h. Using a combination of structural and physiological techniques the structural and physiological features that enable T. loliiformis to tolerate desiccation were investigated. These features include: - (i) a myriad of structural changes such as leaf folding, cell wall folding and vacuole fragmentation that mitigate desiccation stress; - (ii) potential role of sclerenchymatous tissue within leaf folding and radiation protection; - (iii) retention of ~70% chlorophyll in the desiccated state; - (iv) early response of photosynthesis to dehydration by 50% reduction and ceasing completely at 80 and 70% relative water content, respectively; - (v) a sharp increase in electrolyte leakage during dehydration, and; - (vi) confirmation of membrane integrity throughout desiccation and rehydration. Taken together, these results demonstrate that T. loliiformis implements a range of structural and physiological mechanisms that minimise mechanical, oxidative and irradiation stress. These results provide powerful insights into tolerance mechanisms for potential utilisation in the enhancement of stress-tolerance in crop plants.

Arabidopsis thaliana J-class heat shock proteins: cellular stress sensors

Plants are sessile organisms that have evolved a variety of mechanisms to maintain their cellular homeostasis under stressful environmental conditions. Survival of plants under abiotic stress conditions requires specialized group of heat shock protein machinery, belonging to Hsp70:J-protein family. These heat shock proteins are most ubiquitous types of chaperone machineries involved in diverse cellular processes including protein folding, translocation across cell membranes, and protein degradation. They play a crucial role in maintaining the protein homeostasis by reestablishing functional native conformations under environmental stress conditions, thus providing protection to the cell. J-proteins are co-chaperones of Hsp70 machine, which play a critical role by stimulating Hsp70s ATPase activity, thereby stabilizing its interaction with client proteins. Using genome-wide analysis of Arabidopsis thaliana, here we have outlined identification and systematic classification of J-protein co-chaperones which are key regulators of Hsp70s function. In comparison with Saccharomyces cerevisiae model system, a comprehensive domain structural organization, cellular localization, and functional diversity of A. thaliana J-proteins have also been summarized. Electronic supplementary material The online version of this article (doi:10.1007/s10142-009-0132-0) contains supplementary material, which is available to authorized users.

Production of F4 Fimbrial Adhesin in Plants: a Model for Oral Porcine Vaccine against Enterotoxigenic Escherichia coli

F4 fimbriae of enterotoxigenic Escherichia coli (ETEC) are highly stable multimeric structures with a capacity to evoke mucosal immune responses. With these characters F4 offer a unique model system to study oral vaccination against ETEC-induced porcine postweaning diarrhea. Postweaning diarrhea is a major problem in piggeries worldwide and results in significant economic losses. No vaccine is currently available to protect weaned piglets against ETEC infections. Transgenic plants provide an economically feasible platform for large-scale production of vaccine antigens for animal health. In this study, the capacity of transgenic plants to produce FaeG protein, the major structural subunit and adhesin of F4 fimbria, was evaluated. Using the model plant tobacco, the optimal subcellular location for FaeG accumulation was examined. Targeting of FaeG into chloroplasts offered a superior accumulation level of 1% of total soluble proteins (TSP) over the other investigated subcellular locations, namely, the endoplasmic reticulum and the apoplast. Moreover, we determined whether the FaeG protein, when isolated from its fimbrial background and produced in a plant cell, would retain the key properties of an oral vaccine, i.e. stability in gastrointestinal conditions, binding to porcine intestinal F4 receptors (F4R), and inhibition of the F4-possessing (F4+) ETEC attachment to F4R. The chloroplast-derived FaeG protein did show resistance against low pH and proteolysis in the simulated gastrointestinal conditions and was able to bind to the F4R, subsequently inhibiting the F4+ ETEC binding in a dose-dependent manner. To investigate the oral immunogenicity of FaeG protein, the edible crop plant alfalfa was transformed with the chloroplast-targeting construct and equally to tobacco plants, a high-yield FaeG accumulation of 1% of TSP was obtained. A similar yield was also obtained in the seeds of barley, a valuable crop plant, when the FaeG-encoding gene was expressed under an endosperm-specific promoter and subcellularly targeted into the endoplasmic reticulum. Furthermore, desiccated alfalfa plants and barley grains were shown to have a capacity to store FaeG protein in a stable form for years. When the transgenic alfalfa plants were administred orally to weaned piglets, slight F4-specific systemic and mucosal immune responses were induced. Co-administration of the transgenic alfalfa and the mucosal adjuvant cholera toxin enhanced the F4-specific immune response; the duration and number of F4+ E. coli excretion following F4+ ETEC challenge were significantly reduced as compared with pigs that had received nontransgenic plant material. In conclusion, the results suggest that transgenic plants producing the FaeG subunit protein could be used for production and delivery of oral vaccines against porcine F4+ ETEC infections. The findings here thus present new approaches to develop the vaccination strategy against porcine postweaning diarrhea.

Phenotypic plasticity and longevity in plants and animals: cause and effect?

Immobile plants and immobile modular animals outlive unitary animals. This paper discusses competing but not necessarily mutually exclusive theories to explain this extreme longevity, especially from the perspective of phenotypic plasticity. Stem cell immortality, vascular autonomy, and epicormic branching are some important features of the phenotypic plasticity of plants that contribute to their longevity. Monocarpy versus polycarpy can also influence the kind of senescent processes experienced by plants. How density-dependent phenomena affecting the establishment of juveniles in these immobile organisms can influence the evolution of senescence, and consequently longevity, is reviewed and discussed. Whether climate change scenarios will favour long-lived or short-lived organisms, with their attendant levels of plasticity, is also presented.

Nutrition during noninvasive ventilation: clinical determinants and key practical recommendations

Malnutrition and poor nutritional intake have been identified as key issues associated with poorer clinical outcomes in chronic obstructive pulmonary disease (COPD) patients. There is strong evidence showing nutritional support is effective in treating malnutrition in stable COPD, but there is only limited research regarding nutritional status in patients treated with noninvasive ventilation (NIV). The impact of NIV during acute exacerbations of respiratory disease on nutritional status requires further investigation.

Playing the policy game: A review of the barriers and enablers of nutrition policy change

- Objective To progress nutrition policy change and develop more effective advocates, it is useful to consider real-world factors and practical experiences of past advocacy efforts to determine the key barriers and enablers to nutrition policy change. This review aimed to identify and synthesize the enablers and barriers to public policy change within the field of nutrition. - Design Electronic databases were searched systematically for studies examining policymaking in public health nutrition. An interpretive synthesis was undertaken. Setting: International, national, state and local government jurisdictions within high-income, democratic countries. - Results Sixty-three studies were selected for inclusion. Numerous themes were identified explaining the barriers and enablers to policy change, all of which fell under the overarching category, ‘political will’, underpinned by a second major category, ‘public will’. Sub-themes, including pressure from industry; neoliberal ideology; use of emotions and values, and being visible were prevalent in describing links between public will, political will and policy change. - Conclusions The frustration around lack of public policy change in nutrition frequently stems from a belief that policymaking is a rational process in which evidence is used to assess the relative costs and benefits of options. The findings from this review confirm that evidence is only one component of influencing policy change. For policy change to occur there needs to be the political will, and often the public will, for the proposed policy problem and solution. This review presents a suite of enablers which can assist health professionals to influence political and public will in future advocacy efforts.