Intestinal microbiota is a plastic factor responding to environmental changes

Traditionally regarded as stable through the entire lifespan, the intestinal microbiota has now emerged as an extremely plastic entity, capable of being reconfigured in response to different environmental factors. In a mutualistic context, these microbiome fluctuations allow the host to rapidly adjust its metabolic and immunologic performances in response to environmental changes. Several circumstances can disturb this homeostatic equilibrium, inducing the intestinal microbiota to shift from a mutualistic configuration to a disease-associated profile. A mechanistic comprehension of the dynamics involved in this process is needed to deal more rationally with the role of the human intestinal microbiota in health and disease.     

Applying plant genomics to crop improvement

A report of the European Science Foundation-Wellcome Trust Conference on Crop Genomics, Trait Analysis and Breeding, Hinxton, UK, 8-11 November 2006.     

Sequencing crop genomes: approaches and applications

Many challenges face plant scientists, in particular those working on crop production, such as a projected increase in population, decrease in water and arable land, changes in weather patterns and predictability. Advances in genome sequencing and resequencing can and should play a role in our response to meeting these challenges. However, several barriers prevent rapid and effective deployment of these tools to a wide variety of crops. Because of the complexity of crop genomes, de novo sequencing with next-generation sequencing technologies is a process fraught with difficulties that then create roadblocks to the utilization of these genome sequences for crop improvement. Collecting rapid and accurate phenotypes in crop plants is a hindrance to integrating genomics with crop improvement, and advances in informatics are needed to put these tools in the hands of the scientists on the ground.     

Reproduction mode and crop improvement

Summary The author has tried to accumulate data on the reproduction modes of crop plants: autogamy and allogamy in the case of sexuality, involving self-fertility and self-sterility, and different means of vegetative propagation and apomixis. In combination with the state of ploidy and the basic chromosome number the different modes of reproduction exert a considerable influence on population structure and the success or failure of different methods applied in plant breeding. This relates to the use of selection, hybrid vigour (F₁ heterosis), gene recombination, as well as polyploidy and induced or spontaneous mutation. It is pointed out that extranuclear (cytoplasmic) inheritance should not be neglected as a device also in the case of polyploidy and mutation.Transitional stages exist between autogamy and allogamy. Autogamy is obligate in no or at least very few cases. In allogamous species inbreeding and subsequent outcrossing are important features in their improvement by breeding. In dioecious, monoecious and hermaphroditic species the modes of reproduction can be switched into one another by appropriate methods of gene recombination, mutation and selection. Apomictic species, for instance several grasses, display a series of transitions between more or less obligatory apomixis (parthenogenesis and vivipary) and partial or complete sexuality.At the end of the article data are presented to indicate how various modes of reproduction influence the methods applied in the exploration and conservation of plant gene pools.Finally, the pioneer work on plant exploration carried out byVavilov, Zhukovsky and their co-workers is emphasized. Favourable genes, chromosomes and cytoplasms present in natural populations have to be preserved. New favourable genes etc. should be continually produced by mutation. Preservation of old genes and induction of new genes are means of augmenting the breeders' resources in their efforts of continuous crop plant improvement.

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Zusammenfassung Es werden die verschiedenen Formen der Fortpflanzung bei Kulturpflanzen behandelt, wie Auto-und Allogamie bei geschlechtlicher Vermehrung, einschließlich Selbstfertilität und Selbststerilität, und die verschiedenen Möglichkeiten der vegetativen Vermehrung und Apomixis. In Verbindung mit dem Ploidiegrad und der Chromosomengrundzahl haben die verschiedenen Fortpflanzungsformen einen erheblichen Einfluß auf die Populationsstruktur und auf den Erfolg oder Mißerfolg der einzelnen in der Pflanzenzüchtung angewandten Methoden. Das gilt für die Anwendung von Selektion, F₁-Heterosis und Genrekombination ebenso wie für Polyploidie und induzierte oder spontane Mutation. Es wird betont, daß die plasmatische Vererbung, auch im Falle von Polyploidie und Mutation, nicht außer acht gelassen werden sollte.Zwischen Auto- und Allogamie sind Übergangsstadien vorhanden. Autogamie ist in keinem Fall oder wenigstens in sehr wenigen Fällen obligatorisch. Bei allogamen Species sind Inzucht und nachfolgende Kreuzung wesentliche Möglichkeiten für eine Leistungssteigerung durch Züchtung. Bei diözischen, monözischen und hermaphroditen Species kann die Fortpflanzungsform durch geeignete Methoden der Genrekombination, Mutation und Selektion geändert werden. Apomiktische Species, z. B. verschiedene Gräser, zeigen Übergänge zwischen mehr oder weniger obligatorischer Apomixis (Parthenogenesis und Viviparie) und teilweiser oder völliger Sexualität.Am Schluß der Arbeit werden Beispiele gebracht, wie die verschiedenen Fortpflanzungsformen die Methoden beeinflussen, die bei der Erforschung und Erhaltung der pflanzlichen Gen-Pools angewendet werden.Schließlich wird die Pionierarbeit vonVavilov, Zhukovsky und ihren Mitarbeitern gewürdigt.Günstige Gene, Chromosomen und Cytoplasmen, die in natürlichen Populationen vorhanden sind, müssen erhalten bleiben. Neue günstige Gene usw. sollten laufend durch Mutation geschaffen werden. Die Erhaltung der alten Gene und die Induktion neuer sind Hilfsquellen für den Züchter in seinem Bemühen um fortgesetzte Leistungssteigerung der Kulturpflanzen.

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In condensed form this article was presented at the FAO technical conference on Exploration, utilization and conservation of plant gene resources, Rome, September 1967. It is here, with all reverence, dedicated to the memory ofN. I. Vavilov and the noble spirit of his friend and successorP. M. Zhukovsky.     

Genetic coding: approaches to theory construction

A new approach to genetic coding theory, the generalized genetic code (GGC), is presented. It is shown how the GGC reunifies ambiguous codon assignments within the standard genetic code, thereby redefining genetic code universality in a modified form. An extensive survey of ambiguous codings (> 100 assignments) is presented as a critical test of the GGC and all assignments are successfully analyzed within the GGC Finally, the operative nature of biological contexts is investigated and discussed.     

Genetic and genomic approaches to glomerulosclerosis

Chronic kidney disease (CKD) is common, progressive and expensive to manage. Although modifiable risk factors can be treated and outcomes improved, CKD remains a chronic disease with excessive morbidity and mortality. The completion of the human genome sequence and the advent of methodologies to define gene function provide new opportunities to manage and treat patients with CKD and other chronic diseases. Despite the lack of clear correspondence between genotype and phenotype and an obvious Mendelian inheritance pattern, CKD susceptibility has a genetic basis. In this review, we focus on recent studies of familial focal segmental glomerulosclerosis and the discoveries that have resulted from both genetic and genomic approaches used to understand its pathogenesis. Key slit diaphragm proteins were discovered using linkage analyses of these rare causes of glomerulosclerosis and subsequent work has characterized slit diaphragm function in health and disease. Podocyte dysfunction is now recognized as a key contributor to the functional and histologic derangements that characterize glomerular dysfunction in many common causes of CKD. In aggregate, these studies provide a paradigm for approaches to better define mechanisms of CKD and to identify novel therapeutic targets.     

Genetic approaches to disease and regeneration

Cardiovascular disease is largely a consequence of coronary artery blockage through excessive proliferation of smooth muscle cells. It in turn leads to myocardial infarction and permanent and functionally devastating tissue damage to the heart wall. Our studies have revealed that elastin is a primary player in maintaining vascular smooth muscle cells in their dormant state and thus may be a useful therapeutic in vascular disease. By studying zebrafish, which unlike humans, can repair damage to heart muscle, we have begun to uncover some of the genes that seem necessary to undertake the de-differentiation steps that currently fail and prevent the formation of new proliferating cardiomyocytes at the site of damage in a mammalian heart.     

Global crop improvement networks to bridge technology gaps

To ensure future food security, there is an urgent need for improved co-ordination of agricultural research. While advances in biotechnology hold considerable promise, significant technology gaps exist that may reduce their impact. Examples include an incomplete knowledge of target breeding environments, a limited understanding and/or application of optimal crop management practices, and underfunded extension services. A better co-ordinated and more globalized approach to agricultural research through the implementation of Global Crop Improvement Networks (GCIN) is proposed. Such networks could underpin agricultural research and development by providing the following types of services: (i) increased resolution and precision of environmental information, including meteorological data, soil characteristics, hydrological data, and the identification of environmental 'hotspots' for a range of biotic, abiotic, and socio-economic constraints; (ii) augmented research capacity, including network-based variety and crop management trials, faster and more comprehensive diagnosis of emerging constraints, timely sharing of new technologies, opportunities to focus research efforts better by linking groups with similar productivity constraints and complementary skills, and greater control of experimental variables in field-based phenotyping; and (iii) increased communication and impacts via more effective dissemination of new ideas and products, the integration of information globally to elicit well-timed local responses to productivity threats, an increased profile, and the publicity of threats to food security. Such outputs would help target the translation of research from the laboratory into the field while bringing the constraints of rural communities closer to the scientific community. The GCIN could provide a lens which academia, science councils, and development agencies could use to focus in on themes of common interest, and working platforms to integrate novel research approaches on crop adaptation and rural development.     

Alternative approaches to population structure

There are three approaches to DNA identification: tectonic, halieutic and icarian, of which the tectonic is sensible, the halieutic impractical, and the icarian idiotic. The rationale and consequences of these approaches are detailed.Editor's commentsThe author captures the harsh tone that has often characterized the debate over the use of DNA for human identification. It should be mentioned that D.L. Hartl, E.S. Lander and R.C. Lewontin were invited to respond. The positions of these three authors are contained in their papers, listed in the Bibliography. Readers should note, in particular, Budowle and Lander (1994).     

Biotechnological approaches to breeding and cultivation of ornamental crop plants

Recent advances in plant biotechnology hold great potential for the ornamental horticulture industry. In addition to conventional methods, breeders can now introduce genetic variation into ornamentals by the application of recombinant DNA technology. This technology is particularly useful for effecting changes in phenotypic expression encoded by single genes such as corolla and foliage color and texture, stem length, scent, temporal regulation of flowering, vase life of cut flowers and resistance to stressful environments. In part, the commercial success of this technology will depend on developing reliable methods of transformation of ornamentals and on the stability of the introduced or altered genes. In addition, new and improved strategies of in vitro culture have been commercially implemented for the propagation and breeding of a wide variety of ornamental crops and will undoubtedly play a major role in the screening and propagation of chimeric plants developed by recombinant DNA technology.     

Genetic approaches to auxin action

Answers to long-standing questions concerning the molecular mechanism of auxin action and auxin's exact functions in plant growth and development are beginning to be uncovered through studies using mutant and transgenic plants. We review recent work in this area in vascular plants. A number of conclusions can be drawn from these studies. First, auxin appears essential for cell division and viability, as auxin auxotrophs isolated in tissue culture are dependent on auxin for growth and cannot be regenerated into plants even when auxin is supplied exogenously. Secondly, plants with transgenes that alter auxin levels are able to regulate cellular auxin concentrations by synthesis and conjugation; wild-type plants are probably also capable of such regulation. Thirdly, the phenotypes of transgenic plants with altered auxin levels and of mutant plants with altered sensitivity to auxin confirm earlier physiological studies which indicated a role for auxin in regulation of apical dominance, in development of roots and vascular tissue, and in the gravitropic response. Finally, the cloning of a mutationally identified gene important for auxin action, along with accumulating biochemical evidence, hints at a major role for protein degradation in the auxin response pathway.     

Genetic approaches to common diseases

Combined molecular and epidemiological studies are advancing our understanding of the genetic basis of multifactorial diseases. Several of the results obtained during the past year highlight methodological issues associated with these approaches. For example, the affected sib-pair method has been applied successfully to detect linkage between the angiotensinogen gene and susceptibility to hypertension, and a large multi-centre epidemiological study has demonstrated association of a polymorphism of the angiotensin-converting enzyme gene with increased risk of myocardial infarction. The study of Mendelian forms of multifactorial diseases has also led to many new results. These include the characterization of mutations in the glucokinase gene in maturity onset diabetes of the young, localization to chromosome 2 of a gene involved in familial colon cancer, and localization to chromosome 19 of a gene responsible for hemiplegic migraine. New insights have been provided into the genetics of multifactorial disorders such as diabetes and hypertension through the study of animal models. Localization of susceptibility loci in such models has recently led to the identification of new candidate genes that may be implicated in disease.     

Genetic approaches to auxin action

Answers to long-standing questions concerning the molecular mechanism of auxin action and auxin's exact functions in plant growth and development are beginning to be uncovered through studies using mutant and transgenic plants. We review recent work in this area in vascular plants. A number of conclusions can be drawn from these studies. First, auxin appears essential for cell division and viability, as auxin auxotrophs isolated in tissue culture are dependent on auxin for growth and cannot be regenerated into plants even when auxin is supplied exogenously. Secondly, plants with transgenes that alter auxin levels are able to regulate cellular auxin concentrations by synthesis and conjugation; wild-type plants are probably also capable of such regulation. Thirdly, the phenotypes of transgenic plants with altered auxin levels and of mutant plants with altered sensitivity to auxin confirm earlier physiological studies which indicated a role for auxin in regulation of apical dominance, in development of roots and vascular tissue, and in the gravitropic response. Finally, the cloning of a mutationally identified gene important for auxin action, along with accumulating biochemical evidence, hints at a major role for protein degradation in the auxin response pathway.     

Intergeneric somatic hybridization and its application to crop genetic improvement

Related or distant species of cultivated cs are a large pool of many desirable genes. Gene transfer from these species through conventional breeding is difficult owing to post- and pre-zygotic sexual incompatibilities. Somatic hybridization via protoplast fusion is a possible alternative for gene transfer from these species to cultivated crops. Since the early days of somatic hybridization many intergeneric somatic hybrids have been developed through symmetric fusion, asymmetric fusion and microfusion. Somatic hybrids are mainly selected by using markers such as specific media or fusion parents with special features, biochemical mutants, antibiotic resistance and complementation strategy. The hybridity of the regenerants is determined based on morphological, cytological and molecular analysis. The inheritance patterns of nuclear and cytoplasmic genomes in the somatic hybrids are diverse. Nuclear DNA from both fusion parents co-exists congruously in some hybrids with translocation and rearrangement of chromosomes, but spontaneous elimination of chromosomes from either or both fusion parents has been observed very often. In asymmetric fusion, chromosome elimination is an important issue that is a complicated process influenced by many factors, such as irradiation dose, phylogenetic relatedness, ploidy level of fusion parent and regenerants. As for chloroplast genome, uniparental segregation is mainly detected, though co-existence is also reported in some cases. The mitochondrial genome, in contrast to chloroplast, undergoes recombination and very frequent rearrangements. Somatic cell fusion has potential applications for crop genetic improvement by overcoming sexual incompatibility or reproductive barriers, and by realizing novel combinations of nuclear and/or cytoplasmic genomes.     

Electron microscopic approaches to environmental toxicity

The possibilities for the use of fine structural methods in environmental toxicology are briefly summarized with special respect to fine structural consequences of toxic cellular injury and cell death.