Death by design: mechanism and control of apoptosis

Active cellular suicide by apoptosis plays important roles in animal development, tissue homeostasis and a wide variety of diseases, including cancer, AIDS, stroke and many neurodegenerative disorders. A central step in the execution of apoptosis is the activation of an unusual class of cysteine proteases, termed caspases, that are widely expressed as inactive zymogens. Originally, the mechanisms for regulating the caspase-based cell death programme seemed to be different in Caenorhabditis elegans, mammals and insects. However, recent results suggest that these apparent differences in the control of cell death reflect our incomplete knowledge, rather than genuine mechanistic differences between different organisms.     

Energetics of protein folding

The energetics of protein folding determine the 3D structure of a folded protein. Knowledge of the energetics is needed to predict the 3D structure from the amino acid sequence or to modify the structure by protein engineering. Recent developments are discussed: major factors are reviewed and auxiliary factors are discussed briefly. Major factors include the hydrophobic factor (burial of non-polar surface area) and van der Waals interactions together with peptide hydrogen bonds and peptide solvation. The long-standing model for the hydrophobic factor (free energy change proportional to buried non-polar surface area) is contrasted with the packing-desolvation model and the approximate nature of the proportionality between free energy and apolar surface area is discussed. Recent energetic studies of forming peptide hydrogen bonds (gas phase) are reviewed together with studies of peptide solvation in solution. Closer agreement is achieved between the 1995 values for protein unfolding enthalpies in vacuum given by Lazaridis-Archontis-Karplus and Makhatadze-Privalov when the solvation enthalpy of the peptide group is taken from electrostatic calculations. Auxiliary factors in folding energetics include salt bridges and side-chain hydrogen bonds, disulfide bridges, and propensities to form alpha-helices and beta-structure. Backbone conformational entropy is a major energetic factor which is discussed only briefly for lack of knowledge.     

Applying cumulative exergy demand (CExD) indicators to the ecoinvent database

Goal, Scope and Background Exergy has been put forward as an indicator for the energetic quality of resources. The exergy of a resource accounts for the minimal work necessary to form the resource or for the maximally obtainable amount of work when bringing the resource’s components to their most common state in the natural environment. Exergy measures are traditionally applied to assess energy efficiency, regarding the exergy losses in a process system. However, the measure can be utilised as an indicator of resource quality demand when considering the specific resources that contain the exergy. Such an exergy measure indicates the required resources and assesses the total exergy removal from nature in order to provide a product, process or service. In the current work, the exergy concept is combined with a large number of life cycle inventory datasets available with ecoinvent data v1.2. The goal was, first, to provide an additional impact category indicator to Life-Cycle Assessment practitioners. Second, this work aims at making a large source of exergy scores available to scientific communities that apply exergy as a primary indicator for energy efficiency and resource quality demand. Methods The indicator Cumulative Exergy Demand (CExD) is introduced to depict total exergy removal from nature to provide a product, summing up the exergy of all resources required. CExD assesses the quality of energy demand and includes the exergy of energy carriers as well as of non-energetic materials. In the current paper, the exergy concept was applied to the resources contained in the ecoinvent database, considering chemical, kinetic, hydro-potential, nuclear, solar-radiative and thermal exergies. The impact category indicator is grouped into the eight resource categories fossil, nuclear, hydropower, biomass, other renewables, water, minerals, and metals. Exergy characterization factors for 112 different resources were included in the calculations. Results CExD was calculated for 2630 ecoinvent product and process systems. The results are presented as average values and for 26 specific groups containing 1197 products, processes and infrastructure units. Depending on the process/product group considered, energetic resources make up between 9% and 100% of the total CExD, with an average contribution of 88%. The exergy of water contributes on the average to 8% the total exergy demand, but to more than 90% in specific process groups. The average contribution of minerals and metal ores is 4%, but shows an average value as high as 38% and 13%, in metallic products and in building materials, respectively. Looking at individual processes, the contribution of the resource categories varies substantially from these average product group values. In comparison to Cumulative Energy Demand (CED) and the abiotic-resource-depletion category of CML 2001 (CML’01), non-energetic resources tend to be weighted more strongly by the CExD method. Discussion Energy and matter used in a society are not destroyed but only transformed. What is consumed and eventually depleted is usable energy and usable matter. Exergy is a measure of such useful energy. Therefore, CExD is a suitable energy based indicator for the quality of resources that are removed from nature. Similar to CED, CExD assesses energy use, but regards the quality of the energy and incorporates non-energetic materials like minerals and metals. However, it can be observed for non-renewable energy-intensive products that CExD is very similar to CED. Since CExD considers energetic and non-energetic resources on the basis of exhaustible exergy, the measure is comparable to resource indicators like the resource use category of Eco-indicator 99 and the resource depletion category of CML 2001. An advantage of CExD in comparison to these methods is that exergy is an inherent property of the resource. Therefore less assumptions and subjective choices need to be made in setting up characterization factors. However, CExD does not coversocietal demand (distinguishing between basic demand and luxury), availability or scarcity of the resource. As a consequence of the different weighting approach, CExD may differ considerably from the resource category indicators in Eco-indicator 99 and CML 2001. Conclusions The current work shows that the exergy concept can be operationalised in product life cycle assessments. CExD is a suitable indicator to assess energy and resource demand. Due to the consideration of the quality of energy and the integration of non-energetic resources, CExD is a more comprehensive indicator than the widely used CED. All of the eight CExD categories proposed are significant contributors to Cumulative Exergy Demand in at least one of the product groups analysed. In product or service assessments and comparative assertions, a careful and concious selection of the appropriate CExD-categories is required based on the energy and resource quality demand concept to be expressed by CExD. Recommendations and Perspectives A differentiation between the exergy of fossil, nuclear, hydro-potential, biomass, other renewables, water and mineral/metal resources is recommended in order to obtain a more detailed picture of resource quality demand and to recognise trade-offs between resource use, for instance energetic and non-energetic raw materials, or nonrenewable and renewable energies. ESS-Submission Editor: Dr. Gerald Rebitzer (Gerald.Rebitzer@alcan.com)     

Manufacturing and Disposal of Building Materials and Inventorying Infrastructure in ecoinvent (8 pp)

Goal, Scope and Background The present paper describes the goal and scope of building material inventories in the ecoinvent database and gives an overview of its content. The ecoinvent database provides generic life cycle inventories for building material production and related processing. They can be used as background data for different LCA applications. Their geographical and temporal scope is Switzerland or Europe and the year 2000.Methods Data is inventoried as unit processes. Consistency throughout different sources is heeded by systematically estimating missing data. Infrastructure is consequently considered. Different disposal options are modelled.Results and Conclusion The ecoinvent data provide a harmonised basis for different kinds of building materials. Even though not all datasets could be established on the same quality level, the results generally are believed to be comparable. Since data are generic, they are, however, not suitable to directly compare specific products. Disposal is relevant for the environmental burdens of uses of building materials. Complete life cycles have to be assessed. For this purpose, cumulative energy demand (CED) is not a suitable indicator.Recommendation and Perspective In future versions of ecoinvent, data quality could be further improved. The database should be extended to include further building materials from secondary materials. To do so, the methodological treatment of secondary materials needs special attention.     

Death by design: mechanism and control of apoptosis

Active cellular suicide by apoptosis plays important roles in animal development, tissue homeostasis and a wide variety of diseases, including cancer, AIDS, stroke and many neurodegenerative disorders. A central step in the execution of apoptosis is the activation of an unusual class of cysteine proteases, termed caspases, that are widely expressed as inactive zymogens. Originally, the mechanisms for regulating the caspase-based cell death programme seemed to be different in Caenorhabditis elegans, mammals and insects. However, recent results suggest that these apparent differences in the control of cell death reflect our incomplete knowledge, rather than genuine mechanistic differences between different organisms.     

Death by design: mechanism and control of apoptosis

Active cellular suicide by apoptosis plays important roles in animal development, tissue homeostasis and a wide variety of diseases, including cancer, AIDS, stroke and many neurodegenerative disorders. A central step in the execution of apoptosis is the activation of an unusual class of cysteine proteases, termed caspases, that are widely expressed as inactive zymogens. Originally, the mechanisms for regulating the caspase-based cell death programme seemed to be different in Caenorhabditis elegans, mammals and insects. However, recent results suggest that these apparent differences in the control of cell death reflect our incomplete knowledge, rather than genuine mechanistic differences between different organisms.     

Proliferative versus apoptotic functions of caspase-8 : Hetero or homo: The caspase-8 dimer controls cell fate

Caspase-8, the initiator of extrinsically-triggered apoptosis, also has important functions in cellular activation and differentiation downstream of a variety of cell surface receptors. It has become increasingly clear that the heterodimer of caspase-8 with the long isoform of cellular FLIP (FLIP_L) fulfills these pro-survival functions of caspase-8. FLIP_L, a catalytically defective caspase-8 paralog, can interact with caspase-8 to activate its catalytic function. The caspase-8/FLIP_L heterodimer has a restricted substrate repertoire and does not induce apoptosis. In essence, caspase-8 heterodimerized with FLIP_L prevents the receptor interacting kinases RIPK1 and -3 from executing the form of cell death known as necroptosis. This review discusses the latest insights in caspase-8 homo- versus heterodimerization and the implication this has for cellular death or survival. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome.     

Effect of monensin on performance in growing ruminants reared under different environmental temperatures

To evaluate the effect of monensin on the performance of growing cattle under different environmental temperatures, 24 male calves (81.9 ± 7.7 kg mean weight and 100 days old) were distributed in a 2 × 2 factorial arrangement, contrasting 0 or 85 mg monensin/animal per day at 24.3 or 33.2 °C (environmental temperatures). Monensin supplementation increased weight gain (P=0.036), improved feed efficiency (P=0.040), increased ruminal concentrations of volatile fatty acids (VFA; P=0.003) and decreased the molar proportion of butyrate (P=0.034); all effects irrespective of environmental temperatures. A temperature-dependent monensin effect was detected on nitrogen retention (P=0.018) and N retained:N absorbed ratio (P=0.012). Animals fed monensin retained higher N amounts than those of the non-supplemented ones when the environmental temperature was 33.2 °C. Environmental temperature and monensin supplementation showed an interaction effect on urine N concentration (P=0.003). Temperature did not affect N excretion in monensin-fed animals, but increased N excretion in the non-supplemented ones. Monensin increased the crude protein (CP) digestibility (P=0.094) for animals at both temperatures. In conclusion, monensin changes the metabolism of the heat-stressed animals by increasing rumen VFA concentration, digestibility and protein retention, thus improving food use and weight gain.     

Ecology profile of the german high-speed rail passenger transport system,ICE

Intention, Goal, Scope, Background, Objectives  Environmental effects caused by the railway transport services have rarely been investigated in depth from a systemic point of view. A screening LCA, called ecology profile, of the German high-speed passenger train system, the ICE, is presented here, based on a study conducted by the University of Halle and the Deutsche Bahn AG, the major German rail operator. In this study, the resource consumption caused by traction, manufacturing and maintenance of ICE trains, as well as construction and operation of the supporting rail infrastructure and buildings, have been evaluated using cumulative energy demand (CED), cumulative material input per service unit (MIPS) and CO₂ emissions as indicators. Methods  Approximately 200 items of inventory data were collected from DB AG experts, manufacturers, site balances and the associated literature. They were allocated in order to derive 100-person-kilometre-related mass and energy consumption figures. The appropriate CED, MIPS and CO₂ factors were applied in order to quantify the indirect efforts associated with the inventory data. Conclusions  For the reference high-speed route investigated, Hanover-Wuerzburg, the railroad infrastructure does not contribute the high share of resource consumption to the life cycle of the transport service which was expected from other studies. For the reference route, the CED of the infrastructure contributes 13% to the total CED per 100 person kilometres, whilst the energy demand of the traction process dominates the life cycle. Within the railway infrastructure, the construction of tunnels and the heating of rail points during winter time are significant primary-energy active components, whereas the energy requirement for maintaining the railway stations is a minor factor in comparison. The environmental impact of new technologies for designing rail tracks have also been analysed. The new ballastless slab track technology investigated needs higher absolute resource inputs in the construction phase compared with the traditional gravel bed, but due to higher life expectancy, it competes favourably at the 100-person-kilometre level, at least in terms of material requirements. Efforts to reduce the traction energy consumption of the ICE train will have the greatest impact on the CED of the transport system. In summary, a total of 48 kg of solid primary resources are needed for a passenger to travel 100 km by ICE. Recommendations/Outlook  The results presented can be used for modelling other high-speed railway transport systems. A comparison of the ecology profiles of the German, French and Japanese high-speed train systems would be of interest in order to identify potential areas for improvement. Additional studies are needed to evaluate the short-hop, commuter train service. Further efforts should be directed to comparing the infrastructure of the high speed train and that of highway road traffic.