Breeding for abiotic stresses for sustainable agriculture

Using cereal crops as examples, we review the breeding for tolerance to the abiotic stresses of low nitrogen, drought, salinity and aluminium toxicity. All are already important abiotic stress factors that cause large and widespread yield reductions. Drought will increase in importance with climate change, the area of irrigated land that is salinized continues to increase, and the cost of inorganic N is set to rise. There is good potential for directly breeding for adaptation to low N while retaining an ability to respond to high N conditions. Breeding for drought and salinity tolerance have proven to be difficult, and the complex mechanisms of tolerance are reviewed. Marker-assisted selection for component traits of drought in rice and pearl millet and salinity tolerance in wheat has produced some positive results and the pyramiding of stable quantitative trait locuses controlling component traits may provide a solution. New genomic technologies promise to make progress for breeding tolerance to these two stresses through a more fundamental understanding of underlying processes and identification of the genes responsible. In wheat, there is a great potential of breeding genetic resistance for salinity and aluminium tolerance through the contributions of wild relatives.     

Searching for a function for nuclear actin

The abundant cytoskeletal protein actin has numerous cytoplasmic roles. Although there are many reports of the presence of actin in the nucleus, in general they have been discounted as artifactual. However, recent work has begun to provide evidence for important roles for actin in nuclear processes ranging from chromatin remodelling to splicing. In addition, several regulators of actin polymerization are localized to the nucleus or translocate to the nucleus in a regulated manner, suggesting that there is some function of actin in the nucleus that is subject to regulation. This review discusses the evidence for actin in the nucleus and summarizes recent work suggesting that actin or actin-related proteins are involved in the regulation of nuclear processes such as chromatin remodelling.     

Risk factors for rejection for morphological reasons of heart valves for transplantation

The study aim was to identify risk factors for morphological rejection of aortic and pulmonary valves for transplantation that could be used to optimize donor selection. The files of all Dutch heart valve donors, donating in a 2.5 years period, whose hearts were processed at Heart Valve Bank Rotterdam, were reviewed for all factors that could be relevant for valve rejection and related to outcome of morphological assessment of the valves. Valves were retrieved from 813 deceased Dutch donors, 24.1% also donating organs. For 797 aortic and 767 pulmonary valves, who met retrieval criteria, morphological assessment was done. 69.5% of aortic and 37.5% of pulmonary valves were considered unsuitable for transplantation at morphological assessment. Backward stepwise multivariate logistic regression analysis, showed age, cardiac cause of death, cerebrovascular accident as cause of death or in medical history, and number of cardiovascular risk factors in a donor to be independent risk factors for morphological rejection of aortic valves. Age, sex, weight >100 kg and ruptured aortic aneurysm as cause of death were independent risk factors for morphological rejection of pulmonary valves. Being an organ donor was an independent predictor of morphological approval of aortic and pulmonary valves, while hypertension was an independent predictor for morphological approval of aortic valves. Thus, independent factors were identified that are associated with morphological rejection of aortic and pulmonary valves for transplantation, and that could be used to optimize donor selection by preventing unnecessary retrievals, limiting costs, while improving yield per donor with minimal compromise for availability.     

Competition for water for the food system

Although the global agricultural system will need to provide more food for a growing and wealthier population in decades to come, increasing demands for water and potential impacts of climate change pose threats to food systems. We review the primary threats to agricultural water availability, and model the potential effects of increases in municipal and industrial (M&I) water demands, environmental flow requirements (EFRs) and changing water supplies given climate change. Our models show that, together, these factors cause an 18 per cent reduction in the availability of worldwide water for agriculture by 2050. Meeting EFRs, which can necessitate more than 50 per cent of the mean annual run-off in a basin depending on its hydrograph, presents the single biggest threat to agricultural water availability. Next are increases in M&I demands, which are projected to increase upwards of 200 per cent by 2050 in developing countries with rapidly increasing populations and incomes. Climate change will affect the spatial and temporal distribution of run-off, and thus affect availability from the supply side. The combined effect of these factors can be dramatic in particular hotspots, which include northern Africa, India, China, parts of Europe, the western US and eastern Australia, among others.     

Bioethics for human geneticists: models for reasoning and methods for teaching.

The ethical issues raised by the Human Genome Project (HGP) and by human genetics in general are not entirely novel. In fact, the ethical issues surrounding genetic research and the provision of genetic services fit into the evolution of bioethics, a field of inquiry which has its roots in concerns of the 1970s, concerns about the dignity and self-determination of individuals and about the development of medical technologies. Although bioethics has been largely occupied with patient-centered concerns, attention is currently shifting toward socially oriented issues, such as the justice of the existing health-care system. Genetic counseling has already incorporated many of the lessons of early bioethics and, as a profession, adheres to a consultand-centered ethic which reflects the values incorporated into the doctrine of informed consent, which is a cornerstone of bioethics. The mandate of the Ethical, Legal, and Social Implications Program of the HGP--to anticipate ethical problems arising from advances in genetics and to educate the public about genetics--reflects not only the nonpaternalistic approach of early bioethics but also bioethics' increasing attention to the ethical import of systemic and institutional factors, as well as an anticipatory and preventive approach to dealing with ethical concerns. Because bioethics has so much to contribute to current consideration of ethical issues in human genetics, it is important to provide training in ethics to those working in the field. Guidelines for using a case-oriented approach are suggested.     

Biobanks for genomics and genomics for biobanks

Biobanks include biological samples and attached databases. Human biobanks occur in research, technological development and medical activities. Population genomics is highly dependent on the availability of large biobanks. Ethical issues must be considered: protecting the rights of those people whose samples or data are in biobanks (information, autonomy, confidentiality, protection of private life), assuring the non-commercial use of human body elements and the optimal use of samples and data. They balance other issues, such as protecting the rights of researchers and companies, allowing long-term use of biobanks while detailed information on future uses is not available. At the level of populations, the traditional form of informed consent is challenged. Other dimensions relate to the rights of a group as such, in addition to individual rights. Conditions of return of results and/or benefit to a population need to be defined. With 'large-scale biobanking' a marked trend in genomics, new societal dimensions appear, regarding communication, debate, regulation, societal control and valorization of such large biobanks. Exploring how genomics can help health sector biobanks to become more rationally constituted and exploited is an interesting perspective. For example, evaluating how genomic approaches can help in optimizing haematopoietic stem cell donor registries using new markers and high-throughput techniques to increase immunogenetic variability in such registries is a challenge currently being addressed. Ethical issues in such contexts are important, as not only individual decisions or projects are concerned, but also national policies in the international arena and organization of democratic debate about science, medicine and society.     

Science for medicine--time for another reappraisal.

The Amendments to the National Cancer Act of 1974 included a provision for a comprehensive review of the Federal policies and programs for medical research. This would appear to be a particularly timely review since many of the fundamental issues concerning the Government's role in biomedical research are presently in question. These issues include the rationale for public support for basic medical research, public expectations for returns on these investments, establishment of priorities among various research avenues, and a number of derivative as well as ethical questions. Since the professional and scientific communities have been historically successful in gaining public funds for research, a periodic opportunity for public review and consideration would appear to be highly desirable.     

Prospects for gene therapy for cystic fibrosis

Despite advances in conventional treatments for cystic fibrosis (CF), the disease is still associated with significant morbidity and mortality. The cloning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and the understanding of the functions of the CFTR protein have led to the development of novel treatment strategies, including gene therapy. Here, we review the underlying molecular defect in CF cells, and the progress in gene-transfer studies from in vitro work through to clinical trials. We discuss the problems encountered, the end-points used to assess efficacy, and the likely future directions of the field.     

Current strategies for identifying and validating targets for new treatment-shortening drugs for TB

There is an urgent need for new drugs to treat tuberculosis. During the last forty years the only drugs to have been developed are variations on existing ones, but new drug candidates must offer improvements over existing agents. In particular, we require new drugs having novel mechanisms of action that are active against drug-resistant strains and also kill persistent bacilli, thus shortening the length of chemotherapy. Recent advances in our understanding of the biology of Mycobacterium tuberculosis, in particularly the availability of the genome sequence coupled with development of new genetic tools, have greatly contributed to the discovery of potential drug targets for new antituberculars. However, although many potential new drug targets have been identified, greater effort is required in target validation to show properly that they are essential for bacterial growth and survival. In this review, the current drug development pipeline and the strategies employed to identify and validate novel tuberculosis drug targets are presented.     

Prospects for biopesticides for aphid control

Diseases form an important component of the natural enemy complex of aphids. The most common and obvious of these diseases are entomophthoran fungi such asErynia neoaphidis Remaudiere & Herbert,Entomophthora planchoniana Cornu,Zoophthora radicans (Brefeld) Batko andConidiobolus obscurus (Hall & Dunn) Remaudiere & Keller. The pest status of some aphids such as the pea aphid,Acyrthosiphon pisum (Harris), is considerably reduced by natural epizootics of fungal disease. However, disease may contribute little to practical control as it is mainly effective in high density populations when weather conditions are suitable. Introduction of exotic diseases for classical biological control is only rarely possible since most diseases, like their aphid hosts, are distributed world-wide. One exception was the successful introduction into Australia of a strain ofZ. radicans for control of spotted alfalfa aphid,Therioaphis trifolii (Monell) f.maculata in 1979. Attempts to manipulate entomophthoran fungi have had limited success because of problems with mass production, the fragility of the conidia and the need for suitably moist conditions. Hyphomycete fungi such asVerticillium lecanii (Zimm.) Viegas,Metarhizium anisopliae (Metsch.) Sorokin,Beauveria bassiana (Bals.) Vuill. andPaecilomyces spp. are more suitable for development as mycoinsecticides as they are cheap to mass produce and form stable conidia. “Vertalec?”, a formulation ofV. lecanii, has been sold in small quantities commercially in Britain and parts of Europe for many years and used mainly in glasshouses. Recently promising results have been obtained with use ofM. anisopliae for control of lettuce root aphid,Pemphigus bursarius (L.) in the UK. Laboratory studies on selected isolates ofB. bassiana andPaecilomyces spp. show a promising level of activity. Problems may occur with these species as they can kill aphid predators such as coccinelids. In addition, more research is needed on developing improved formulations which enable control to be achieved under low humidity conditions.     

Autophagy: for better or for worse

Autophagy is a lysosomal degradation pathway that degrades damaged or superfluous cell components into basic biomolecules, which are then recycled back into the cytosol. In this respect, autophagy drives a flow of biomolecules in a continuous degradation-regeneration cycle. Autophagy is generally considered a pro-survival mechanism protecting cells under stress or poor nutrient conditions. Current research clearly shows that autophagy fulfills numerous functions in vital biological processes. It is implicated in development, differentiation, innate and adaptive immunity, ageing and cell death. In addition, accumulating evidence demonstrates interesting links between autophagy and several human diseases and tumor development. Therefore, autophagy seems to be an important player in the life and death of cells and organisms. Despite the mounting knowledge about autophagy, the mechanisms through which the autophagic machinery regulates these diverse processes are not entirely understood. In this review, we give a comprehensive overview of the autophagic signaling pathway, its role in general cellular processes and its connection to cell death. In addition, we present a brief overview of the possible contribution of defective autophagic signaling to disease.     

Evidence for an essential role for arginyl residues for yeast phosphoglycerate kinase.

Reaction of yeast phosphoglycerate kinase with either butanedione or cyclohexanedione can result in modification of up to all 13 arginyl residues with total loss of activity; however, extrapolation to zero activity for partially modified preparations indicates that up to 7 arginyls are essential. Whereas 20 mm 3-phosphoglycerate affords partial protection of activity toward both reagents, 20 mm MgATP affords complete protection of activity and protects 2 arginyls against modification by butanedione and 1 arginyl against modification by cyclohexanedione. With butanedione the modification could be reversed with total recovery of activity, suggesting that only arginyl groups were modified, which is consistent with the amino acid analysis of the modified protein. Only at high cyclohexanedione concentrations or long reaction times was a yellow product obtained that showed loss of lysyl residues. Circular dichroism spectra show that even when all the arginyls are modified by butanedione or up to 10 modified by cyclohexanedione there is no change observed in the far or near ultraviolet, indicating that there is no detectable conformational change concomitant with modification, which is confirmed by hydrodynamic studies. It is concluded that at least one, possibly two, arginyls of yeast phosphoglycerate kinase are essential for its action on ATP.     

Protocols for data generation for predictive modeling

Summary Essential to the development of useful predictive models for foods is the collection of appropriate data. Within the UK Predictive Food Microbiology Program, a series of documents have been produced to aid the standardization of data collection by a number of laboratories. Documents include a protocols form, notes on experimental design, notes on the accuracy of counts by plating, the preferred method of calculating a plate count value, preferred MPN tables and the preferred methods of recording data values. These documents have proven useful in aiding collaboration between laboratories.     

Theory for designing nature reserves for single species

We examine the question of the optimal number of reserves that should be established to maximize the persistence of a species. We assume that the mean time to extinction of a single population increases as a power of the habitat area, that there is a certain amount of habitat to be reserved, and that the aim is to determine how this habitat is most efficiently divided. The optimal configuration depends on whether the management objective is to maximize the mean time to extinction or minimize the risk of extinction. When maximizing the mean time to extinction, the optimal number of independent reserves does not depend on the amount of available habitat for the reserve system. In contrast, the risk of extinction is minimized when individual reserves are equal to the optimal patch size, making the optimal number of reserves linearly proportional to the amount of available habitat. A model that includes dispersal and correlation in the incidence of extinction demonstrates the importance of considering the relative rate at which these two factors decrease with distance between reserves. A small number of reserves is optimal when the mean time to extinction increases rapidly with habitat area or when risks of extinction are high.     

Biofortification for combating 'hidden hunger' for iron

Micronutrient deficiencies are responsible for so-called 'hidden undernutrition'. In particular, iron (Fe) deficiency adversely affects growth, immune function and can cause anaemia. However, supplementation of iron can exacerbate infectious diseases and current policies of iron therapy carefully evaluate the risks and benefits of these interventions. Here we review the approaches of biofortification of valuable crops for reducing 'hidden undernutrition' of iron in the light of the latest nutritional and medical advances. The increase of iron and prebiotics in edible parts of plants is expected to improve health, whereas the reduction of phytic acid concentration, in crops valuable for human diet, might be less beneficial for the developed countries, or for the developing countries exposed to endemic infections.     

Carbon for soils,not soils for carbon

The role of soil organic carbon (SOC) sequestration as a ‘win-win’ solution to both climate change and food insecurity receives an increasing promotion. The opportunity may be too good to be missed! Yet the tremendous complexity of the two issues at stake calls for a detailed and nuanced examination of any potential solution, no matter how appealing. Here, we critically re-examine the benefits of global SOC sequestration strategies on both climate change mitigation and food production. While estimated contributions of SOC sequestration to climate change vary, almost none take SOC saturation into account. Here, we show that including saturation in estimations decreases any potential contribution of SOC sequestration to climate change mitigation by 53%–81% towards 2100. In addition, reviewing more than 21 meta-analyses, we found that observed yield effects of increasing SOC are inconsistent, ranging from negative to neutral to positive. We find that the promise of a win-win outcome is confirmed only when specific land management practices are applied under specific conditions. Therefore, we argue that the existing knowledge base does not justify the current trend to set global agendas focusing first and foremost on SOC sequestration. Away from climate-smart soils, we need a shift towards soil-smart agriculture, adaptative and adapted to each local context, and where multiple soil functions are quantified concurrently. Only such comprehensive assessments will allow synergies for land sustainability to be maximised and agronomic requirements for food security to be fulfilled. This implies moving away from global targets for SOC in agricultural soils. SOC sequestration may occur along this pathway and contribute to climate change mitigation and should be regarded as a co-benefit.     

Prospects for using pyroproxyfen-treated targets for tsetse control

Using¹⁴C cholesterol as a marker a positive correlation was established between the amount of oil (a chlorinated n-alkane containing 43–46% chlorine, ‘cereclor S45’) picked up by an adult tsetse fly exposed by tarsal contact to a treated surface and the duration of such exposure. Only a poor uptake was achieved from netting surfaces treated with less than 50% oil in acetone. Terylene netting treated with radioactive pyriproxyfen, [1-methyl-2-(4-phenoxyphenoxy)ethoxy] pyridine, dissolved in cereclor, was exposed in the field for a year. After 9 months 20% of the original radioactivity remained and was shown to be 95% authentic pyriproxyfen. Brief tarsal contact (up to 5 seconds) with such netting, by adult females ofGlossina morsitans morsitans Westwood, reduced the viability of their offspring to 28–43% of untreated control values. The effect was greatest in the reproductive cycle immediately following contact. Between 10 and 12 months after treatment of the fabric the radioactivity fell to only 7% of the original level but was associated mainly (>80%) with intact pyriproxyfen. Exposure of female flies to this netting resulted in a positive correlation between the duration of exposure and the extent of suppression of offspring viability, such that 2 min was sufficient to reduce offspring viability to zero for the life of the female. Traps or targets impregnated with conventional formulations of pyrethroids to kill tsetse would have lost all their activity by this time. Results are discussed in terms of the prospects for using pyriproxyfen-treated targets to sterilize female tsetse directly and also indirectly through the contamination of males prior to mating through contact with such targets.     

Rationale for Leptin-Replacement Therapy for Severe Lipodystrophy

ObjectiveTo review evidence supporting the hypothesis that metabolic manifestations of lipodystrophy result from leptin deficiency and that leptin replacement may be a viable treatment for generalized lipodystrophy.MethodsThis review results from the authors’ collective clinical experience and a comprehensive MEDLINE search of the English-language literature (1998 to 2009) on “leptin and lipodystrophy.”ResultsSevere lipodystrophy syndromes are characterized by loss of subcutaneous adipose tissue and thus a relative deficiency of the adipocyte-secreted hormone leptin. Several small, nonrandomized, open-label trials in a composite total of more than 100 patients with severe lipodystrophy not related to human immunodeficiency virus infection have evaluated the efficacy and safety of recombinant human methionyl leptin (metreleptin) therapy. Variables observed to improve after treatment with metreleptin include glycemic control, insulin sensitivity, plasma triglycerides, caloric intake, liver volume and lipid content, intramyocellular lipid content, and neuroendocrine and immunologic end points. In these studies, metreleptin treatment was well tolerated. Typical daily replacement doses for metreleptin were 0.06 to 0.08 mg/kg for female patients and 0.04 mg/kg for male patients, administered by subcutaneous injection twice daily. Although metreleptin is not yet approved for routine clinical use, it is available by means of expanded access provisions for patients with severe lipodystrophy and associated metabolic abnormalities.ConclusionEvidence published in the medical literature indicates that treating severe lipodystrophy as a leptin deficiency syndrome can improve the metabolic outcomes in affected patients. (Endocr Pract. 2010;16:324-333)     

Modeling for Understanding v. Modeling for Numbers

I draw a distinction between Modeling for Numbers, which aims to address how much, when, and where questions, and Modeling for Understanding, which aims to address how and why questions. For-numbers models are often empirical, which can be more accurate than their mechanistic analogues as long as they are well calibrated and predictions are made within the domain of the calibration data. To extrapolate beyond the domain of available system-level data, for-numbers models should be mechanistic, relying on the ability to calibrate to the system components even if it is not possible to calibrate to the system itself. However, development of a mechanistic model that is reliable depends on an adequate understanding of the system. This understanding is best advanced using a for-understanding modeling approach. To address how and why questions, for-understanding models have to be mechanistic. The best of these for-understanding models are focused on specific questions, stripped of extraneous detail, and elegantly simple. Once the mechanisms are well understood, one can then decide if the benefits of incorporating the mechanism in a for-numbers model is worth the added complexity and the uncertainty associated with estimating the additional model parameters.