Assessing the safety of stem cell therapeutics

Unprecedented developments in stem cell research herald a new era of hope and expectation for novel therapies. However, they also present a major challenge for regulators since safety assessment criteria, designed for conventional agents, are largely inappropriate for cell-based therapies. This article aims to set out the safety issues pertaining to novel stem cell-derived treatments, to identify knowledge gaps that require further research, and to suggest a roadmap for developing safety assessment criteria. It is essential that regulators, pharmaceutical providers, and safety scientists work together to frame new safety guidelines, based on "acceptable risk," so that patients are adequately protected but the safety "bar" is not set so high that exciting new treatments are lost.     

Assessing habitat quality of farm-dwelling house sparrows in different agricultural landscapes

Having historically been abundant throughout Europe, the house sparrow (Passer domesticus) has in recent decades suffered severe population declines in many urban and rural areas. The decline in rural environments is believed to be caused by agricultural intensification, which has resulted in landscape simplification. We used giving-up densities (GUDs) of house sparrows feeding in artificial food patches placed in farmlands of southern Sweden to determine habitat quality during the breeding season at two different spatial scales: the landscape and the patch scale. At the landscape scale, GUDs were lower on farms in homogeneous landscapes dominated by crop production compared to more heterogeneous landscapes with mixed farming or animal husbandry. At the patch level, feeding patches with a higher predation risk (caused by fitting a wall to the patch to obstruct vigilance) had higher GUDs. In addition, GUDs were positively related to population size, which strongly implies that GUDs reflect habitat quality. However, the increase followed different patterns in homogeneous and heterogeneous landscapes, indicating differing population limiting mechanisms in these two environments. We found no effect of the interaction between patch type and landscape type, suggesting that predation risk was similar in both landscape types. Thus, our study suggests that simplified landscapes constitute a poorer feeding environment for house sparrows during breeding, that the population-regulating mechanisms in the landscapes differ, but that predation risk is the same across the landscape types.     

Assessing the impacts of agricultural intensification on biodiversity: a British perspective

Agricultural intensification is best considered as the level of human appropriation of terrestrial net primary production. The global value is set to increase from 30%, increasing pressures on biodiversity. The pressures can be classified in terms of spatial scale, i.e. land cover, landscape management and crop management. Different lowland agricultural landscapes in Great Britain show differences among these pressures when habitat diversity and nutrient surplus are used as indicators. Eutrophication of plants was correlated to N surplus, and species richness of plants correlated with broad habitat diversity. Bird species diversity only correlated with habitat diversity when the diversity of different agricultural habitats was taken into account. The pressures of agricultural change may be reduced by minimizing loss of large habitats, minimizing permanent loss of agricultural land, maintaining habitat diversity in agricultural landscapes in order to provide ecosystem services, and minimizing pollution from nutrients and pesticides from the crops themselves. While these pressures could potentially be quantified using an internationally consistent set of indicators, their impacts would need to be assessed using a much larger number of locally applicable biodiversity indicators.     

Assessing life cycle impacts from changes in agricultural practices of crop production

The International Journal of Life Cycle Assessment - This paper presents an improved methodological approach for studying life cycle impacts (especially global warming) from changes in crop...     

Assessing agricultural soil acidification and nutrient management in life cycle assessment

Purpose  

This paper describes part of the first detailed environmental life cycle assessment (LCA) of Australian red meat (beef and sheep meat) production. The study was intended to assist the methodological development of life cycle impact assessment by examining the feasibility of new indicators for natural resource management (NRM) issues relevant to soil management in agricultural LCA. This paper is intended to describe the NRM indicators directly related to agricultural soil chemistry.     

农用化学品污染对土壤微生物群落DNA序列多样性影响研究

采用ＲＡＰＤ分子遗传标记技术研究了农用化学品不同使用环境下的４种土壤微生物群落ＤＮＡ序列多样性的变化。结果表明,４种土壤微生物群落ＤＮＡ序列在其丰富度、多样性指数、均匀度等方面均存在差异;农用化学品的使用会对土壤微生物群落在ＤＮＡ分子水平上的多样性产生影响;而冰同的农用化学品对土壤微生物群落ＤＮＡ序列多样性影响各不相同：化肥污染会引起某些土壤微生物的富集和一些微生物物种的丧失;农药杂会引起土壤微生     

Proteomic analysis and in vitro developmental toxicity tests for mechanism-based safety evaluation of chemicals

Mechanism-based safety evaluation and reduction of animal use are important issues in recent developmental toxicology. In vitro developmental toxicity tests with proteomic analysis are the most promising solution to these issues. Groebe et al. systematically applied proteomic analysis to the embryonic stem cell test, a validated in vitro developmental toxicity test, and found protein-expression changes induced by model test chemicals selected from various categories of toxicity. Cluster analysis of all the proteins with expression changes classified the test chemicals into two groups: highly embryotoxic chemicals and non- or weakly embryotoxic chemicals. In addition, some protein biomarker candidates that were known to be involved in normal development were identified. Although further mechanistic investigations are needed, the use of in vitro developmental toxicity tests with proteomic analysis will contribute to mechanism-based safety evaluation with minimal use of animals.     

农产品质量安全的生态观认识

可持续农业概念提出30多年,世界各地区都有不同的认识.我国类似的概念被称作生态农业,历经几十年的实践,在理论、模式及配套技术上都有了认识总结,但迄今仍然缺乏明确界定的应用指导.欧盟提出的有机农业模式现在被广为接受,但其受益群体和承担的社会责任、生态责任均有一定的局限性.针对以上问题,本文从生态学角度出发,分析了生态失衡弊端对农产品质量安全的负面影响,提出了可持续安全农产品概念.支持该概念的农业生产模式追求两方面的价值,一是拥有一个健康的生态圈环境作为农业产业平台,二是能从这个产业平台可持续地获取安全农产品.围绕该概念的核心价值,设计了生产可持续安全农产品的农业构建模式,同时提出了对不可逆、不可控、难修复的农艺措施在改良之前放弃使用的原则.最后通过与有机农业在承担责任、受益群体、农艺措施选用以及对转基因技术的认识等方面进行对比,反证可持续安全农业模式下生产的农产品在数量安全、质量安全上的先进性.     

Assessing freshwater ecotoxicity of agricultural products in life cycle assessment (LCA): a case study of wheat using French agricultural practices databases and USEtox model

Purpose  

A life cycle assessment (LCA) was conducted on winter wheat, based on real agricultural practices databases, on a sample divided into four production scenarios. The main objectives of this study are (1) to assess the environmental impact of winter wheat, using an LCA covering field practices, and the transport and storage of grain until it is sold to a miller; (2) to use the USEtox model (Rosenbaum et al. in Int J Life Cycle Assess 13:532–546, 2008) to assess the part of the total freshwater ecotoxicity impact due to pesticide use, its variability among plots, and to identify the active ingredients with the strongest impact; (3) and with the help of fungicide, insecticide, herbicide experts, to identify active ingredients to replace these high-impact pesticides and estimate the effect of such a substitution on total freshwater ecotoxicity.     

Assessing key safety concerns of a Wolbachia-based strategy to control dengue transmission by Aedes mosquitoes

Mosquito-borne diseases such as dengue fever, chikungunya or malaria affect millions of people each year and control solutions are urgently needed. An international research program is currently being developed that relies on the introduction of the bacterial endosymbiont Wolbachia pipientis into Aedes aegypti to control dengue transmission. In order to prepare for open-field testing releases of Wolbachia-infected mosquitoes, an intensive social research and community engagement program was undertaken in Cairns, Northern Australia. The most common concern expressed by the diverse range of community members and stakeholders surveyed was the necessity of assuring the safety of the proposed approach for humans, animals and the environment. To address these concerns a series of safety experiments were undertaken. We report in this paper on the experimental data obtained, discuss the limitations of experimental risk assessment and focus on the necessity of including community concerns in scientific research.     

Assessing the remotely sensed Drought Severity Index for agricultural drought monitoring and impact analysis in North China

Remote sensing can provide real-time and dynamic information for terrestrial ecosystems, facilitating effective drought monitoring. A recently proposed remotely sensed Drought Severity Index (DSI), integrating both vegetation condition and evapotranspiration information, shows considerable potential for drought monitoring at the global scale. However, there has been little research on regional DSI applications, especially concerning agricultural drought. As the most important winter wheat producing region in China, North China has suffered from frequent droughts in recent years, demonstrating high demand for efficient agricultural drought monitoring and drought impact analyses. In this paper, the capability of the MODIS DSI for agricultural drought monitoring was evaluated and the drought impacts on winter wheat yield were assessed for 5 provinces in North China. First, the MODIS DSI was compared with precipitation and soil moisture at the province level to examine its capability for characterizing moisture status. Then specifically for agricultural drought monitoring, the MODIS DSI was evaluated against agricultural drought severity at the province level. The impacts of agricultural drought on winter wheat yield during the main growing season were also explored using 8-day MODIS DSI data. Overall, the MODIS DSI is generally effective for characterizing moisture conditions at the province level, with varying ability during the main winter wheat growing season and the best relationship observed in April during the jointing and booting stages. The MODIS DSI agrees well with agricultural drought severity at the province level, with better performance in rainfed-dominated than irrigation-dominated regions. Drought shows varying impacts on winter wheat yield at different stages of the main growing season, with the most significant impacts found during the heading and grain-filling stages, which could be used as the key alert period for effective agricultural drought monitoring.     

Modular and scalable biocatalytic tools for practical safety,health and environmental improvements in the production of speciality chemicals

Biocatalytic tools for both end-of-the-pipe solutions and direct reaction methodology have been developed for the improvement of practical oxidations. The identification of bottlenecks and limitations in biocatalytic Baeyer-Villiger oxidations, and the comparison of scalable process designs to overcome these limitations, have shown the direction for improvements. The first kilogram-scale asymmetric microbial Baeyer-Villiger oxidation with optimized productivity has been realized by the combination of a resin-based in-situ SFPR strategy together with micro-bubble aeration. Regioselective asymmetric dihydroxylation of aromatic nitriles has been achieved by recombinant chlorobenzenedioxygenase. The introduction of novel biocatalytic tools for key catalytic asymmetric transformations will change chemical manufacturing in the 21st century.     

Modular and scalable biocatalytic tools for practical safety, health and environmental improvements in the production of speciality chemicals

Biocatalytic tools for both end-of-the-pipe solutions and direct reaction methodology have been developed for the improvement of practical oxidations. The identification of bottlenecks and limitations in biocatalytic Baeyer-Villiger oxidations, and the comparison of scalable process designs to overcome these limitations, have shown the direction for improvements. The first kilogram-scale asymmetric microbial Baeyer-Villiger oxidation with optimized productivity has been realized by the combination of a resin-based in-situ SFPR strategy together with micro-bubble aeration. Regioselective asymmetric dihydroxylation of aromatic nitriles has been achieved by recombinant chlorobenzenedioxygenase. The introduction of novel biocatalytic tools for key catalytic asymmetric transformations will change chemical manufacturing in the 21st century.     

Scaling up of renewable chemicals

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Enzymatic oxidation of xenobiotic chemicals

Studies with biomimetic models can yield considerable insight into mechanisms of enzymatic catalysis. The discussion above indicates how such information has been important in the cases of flavoproteins, hemoproteins, and, to a lesser extent, the copper protein dopamine beta-hydroxylase. Some of the moieties that we generally accept as intermediates (i.e., high-valent iron oxygen complex in cytochrome P-450 reactions) would be extremely hard to characterize were it not for biomimetic models and more stable analogs such as peroxidase Compound I complexes. Although biomimetic models can be useful, we do need to keep them in perspective. It is possible to alter ligands and aspects of the environment in a way that may not reflect the active site of the protein. Eventually, the model work needs to be carried back to the proteins. We have seen that diagnostic substrates can be of considerable use in understanding enzymes and examples of elucidation of mechanisms through the use of rearrangements, mechanism-based inactivation, isotope labeling, kinetic isotope effects, and free energy relationships have been given. The point should be made that a myriad of approaches need to be applied to the study of each enzyme, for there is potential for misleading information if total reliance is placed on a single approach. The point also needs to be made that in the future we need information concerning the structures of the active sites of enzymes in order to fully understand them. Of the enzymes considered here, only a bacterial form of cytochrome P-450 (P-450cam) has been crystallized. The challenge to determine the three-dimensional structures of these enzymes, particularly the intrinsic membrane proteins, is formidable, yet our further understanding of the mechanisms of enzyme catalysis will remain elusive as long as we have to speak of putative specific residues, domains, and distances in anecdotal terms. The point should be made that there is actually some commonality among many of the catalytic mechanisms of oxidation, even among proteins with different structures and prosthetic groups. Thus, we see that cytochrome P-450 has some elements of a peroxidase and vice versa; indeed, the chemistry at the prosthetic group is probably very similar and the overall chemistry seems to be induced by the protein structure. The copper protein dopamine beta-hydroxylase appears to proceed with chemistry similar to that of the hemoprotein cytochrome P-450 and, although not so thoroughly studied, the non-heme iron protein P. oleovarans omega-hydroxylase.(ABSTRACT TRUNCATED AT 400 WORDS)