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  • 1
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 295-318 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Toroidal DNA condensates have attracted the attention of biophysicists, biochemists, and polymer physicists for more than thirty years. In the biological community, the quest to understand DNA toroid formation has been motivated by its relevance to gene packing in certain viruses and by the potential use of DNA toroids in artificial gene delivery (e.g., gene therapy). In the physical sciences, DNA toroids are appreciated as a superb model system for studying particle formation by the collapse of a semiflexible, polyelectrolyte polymer. This review focuses on experimental studies from the past few years that have significantly increased our understanding of DNA toroid structure and the mechanism of their formation. Highlights include structural studies that show the DNA strands within toroids to be packed in an ideal hexagonal lattice, and also in regions with a nonhexagonal lattice that are required by the topological constraints associated with winding DNA into a toroid. Recent studies of DNA toroid formation have also revealed that toroid size limits result from a complex interplay between kinetic and thermodynamic factors that govern both toroid nucleation and growth. The work discussed in this review indicates that it will ultimately be possible to obtain substantial control over DNA toroid dimensions.
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  • 2
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 267-294 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: With genome sequencing nearing completion for the model organisms used in biomedical research, there is a rapidly growing appreciation that proteomics, the study of covalent modification to proteins, and transcriptional regulation will likely dominate the research headlines in the next decade. Protein methylation plays a central role in both of these fields, as several different residues (Arg, Lys, Gln) are methylated in cells and methylation plays a central role in the "histone code" that regulates chromatin structure and impacts transcription. In some cases, a single lysine can be mono-, di-, or trimethylated, with different functional consequences for each of the three forms. This review describes structural aspects of methylation of histone lysine residues by two enzyme families with entirely different structural scaffolding (the SET proteins and Dot1p) and methylation of protein arginine residues by PRMTs.
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  • 3
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 153-171 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Potassium (K+) channels are tetrameric membrane-spanning proteins that provide a selective pore for the conductance of K+ across the cell membranes. These channels are most remarkable in their ability to discriminate K+ from Na+ by more than a thousandfold and conduct at a throughput rate near diffusion limit. The recent progress in the structural characterization of K+ channel provides us with a unique opportunity to understand their function at the atomic level. With their ability to go beyond static structures, molecular dynamics simulations based on atomic models can play an important role in shaping our view of how ion channels carry out their function. The purpose of this review is to summarize the most important findings from experiments and computations and to highlight a number of fundamental mechanistic questions about ion conduction and selectivity that will require further work.
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  • 4
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 91-118 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Proteins have become accessible targets for chemical synthesis. The basic strategy is to use native chemical ligation, Staudinger ligation, or other orthogonal chemical reactions to couple synthetic peptides. The ligation reactions are compatible with a variety of solvents and proceed in solution or on a solid support. Chemical synthesis enables a level of control on protein composition that greatly exceeds that attainable with ribosome-mediated biosynthesis. Accordingly, the chemical synthesis of proteins is providing previously unattainable insight into the structure and function of proteins.
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  • 5
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 415-440 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: A powerful approach to understanding protein enzyme catalysis is to examine the structural context of essential amino acid side chains whose deletion or modification negatively impacts catalysis. In principle, this approach can be even more powerful for RNA enzymes, given the wide variety and subtlety of functionally modified nucleotides now available. Numerous recent success stories confirm the utility of this approach to understanding ribozyme function. An anomaly, however, is the hammerhead ribozyme, for which the structural and functional data do not agree well, preventing a unifying view of its catalytic mechanism from emerging. To delineate the hammerhead structure-function comparison, we have evaluated and distilled the large body of biochemical data into a consensus set of functional groups unambiguously required for hammerhead catalysis. By examining the context of these functional groups within available structures, we have established a concise set of disagreements between the structural and functional data. The number and relative distribution of these inconsistencies throughout the hammerhead reaffirms that an extensive conformational rearrangement from the fold observed in the crystal structure must be necessary for cleavage to occur. The nature and energetic driving force of this conformational isomerization are discussed.
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  • 6
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 399-414 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: The development of single-molecule detection and manipulation has allowed us to monitor the behavior of individual biological molecules and molecular complexes in real time. This approach significantly expands our capability to characterize complex dynamics of biological processes, allowing transient intermediate states and parallel kinetic pathways to be directly observed. Exploring this capability to elucidate complex dynamics, recent single-molecule experiments on RNA folding and catalysis have improved our understanding of the folding energy landscape of RNA and allowed us to better dissect complex RNA catalytic reactions, including translation by the ribosome.
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  • 7
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 173-199 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Water plays a central role in the structures and properties of biomoleculesĐ??proteins, nucleic acids, and membranesĐ??and in their interactions with ligands and drugs. Over the past half century, our understanding of water has been advanced significantly owing to theoretical and computational modeling. However, like the blind men and the elephant, different models describe different aspects of water's behavior. The trend in water modeling has been toward finer-scale properties and increasing structural detail, at increasing computational expense. Recently, our labs and others have moved in the opposite direction, toward simpler physical models, focusing on more global propertiesĐ??water's thermodynamics, phase diagram, and solvation properties, for exampleĐ??and toward less computational expense. Simplified models can guide a better understanding of water in ways that complement what we learn from more complex models. One ultimate goal is more tractable models for computer simulations of biomolecules. This review gives a perspective from simple models on how the physical properties of waterĐ??as a pure liquid and as a solventĐ??derive from the geometric and hydrogen bonding properties of water.
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  • 8
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 379-398 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Structural data on protein-DNA complexes provide clues for understanding the mechanism of protein-DNA recognition. Although the structures of a large number of protein-DNA complexes are known, the mechanisms underlying their specific binding are still only poorly understood. Analysis of these structures has shown that there is no simple one-to-one correspondence between bases and amino acids within protein-DNA complexes; nevertheless, the observed patterns of interaction carry important information on the mechanisms of protein-DNA recognition. In this review, we show how the patterns of interaction, either observed in known structures or derived from computer simulations, confer recognition specificity, and how they can be used to examine the relationship between structure and specificity and to predict target DNA sequences used by regulatory proteins.
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  • 9
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 457-483 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The field of lymphatic research has been recently invigorated by the identification of genes and mechanisms that control various aspects of lymphatic development. We are beginning to understand how, starting from a subgroup of embryonic venous endothelial cells, the whole lymphatic system forms in a stepwise manner. The generation of genetically engineered mice with defects in different steps of the lymphangiogenic program has provided models that are increasing our understanding of the lymphatic system in health and disease. This knowledge, in turn, should lead to the development of better diagnostic methods and treatments of lymphatic disorders and tumor metastasis.
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  • 10
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 47-79 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Mixed mating, in which hermaphrodite plant species reproduce by both self- and cross-fertilization, presents a challenging problem for evolutionary biologists. Theory suggests that inbreeding depression, the main selective factor opposing the evolution of selfing, can be purged with self-fertilization, a process that is expected to yield pure strategies of either outcrossing or selfing. Here we present updated evidence suggesting that mixed mating systems are frequent in seed plants. We outline the floral and pollination mechanisms that can lead to intermediate outcrossing, review the theoretical models that address the stability of intermediate outcrossing, and examine relevant empirical evidence. A comparative analysis of estimated inbreeding coefficients and outcrossing rates suggests that mixed mating often evolves despite strong inbreeding depression. The adaptive significance of mixed mating has yet to be fully explained for any species. Recent theoretical and empirical work suggests that future progress will come from a better integration of studies of floral mechanisms, genetics, and ecology, and recognition of how selective pressures vary in space and time.
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  • 11
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 191-218 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: We explore empirical and theoretical evidence for the functional significance of plant-litter diversity and the extraordinary high diversity of decomposer organisms in the process of litter decomposition and the consequences for biogeochemical cycles. Potential mechanisms for the frequently observed litter-diversity effects on mass loss and nitrogen dynamics include fungi-driven nutrient transfer among litter species, inhibition or stimulation of microorganisms by specific litter compounds, and positive feedback of soil fauna due to greater habitat and food diversity. Theory predicts positive effects of microbial diversity that result from functional niche complementarity, but the few existing experiments provide conflicting results. Microbial succession with shifting enzymatic capabilities enhances decomposition, whereas antagonistic interactions among fungi that compete for similar resources slow litter decay. Soil-fauna diversity manipulations indicate that the number of trophic levels, species identity, and the presence of keystone species have a strong impact on decomposition, whereas the importance of diversity within functional groups is not clear at present. In conclusion, litter species and decomposer diversity can significantly influence carbon and nutrient turnover rates; however, no general or predictable pattern has emerged. Proposed mechanisms for diversity effects need confirmation and a link to functional traits for a comprehensive understanding of how biodiversity interacts with decomposition processes and the consequences of ongoing biodiversity loss for ecosystem functioning.
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  • 12
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 445-466 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Investigation into model selection has a long history in the statistical literature. As model-based approaches begin dominating systematic biology, increased attention has focused on how models should be selected for distance-based, likelihood, and Bayesian phylogenetics. Here, we review issues that render model-based approaches necessary, briefly review nucleotide-based models that attempt to capture relevant features of evolutionary processes, and review methods that have been applied to model selection in phylogenetics: likelihood-ratio tests, AIC, BIC, and performance-based approaches.
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  • 13
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 295-317 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: One of the greatest mass extinctions in Earth's history occurred at the end of the Cretaceous era, sixty-five million years (Myr) ago. Considerable evidence indicates that the impact of a large asteroid or comet was the ultimate cause of this extraordinary event. At the time of mass extinction, the organic flux to the deep sea collapsed, and production of calcium carbonate by marine plankton radically declined. These biogeochemical processes did not fully recover for a few million years. The drastic decline and long lag in final recovery of these processes are most simply explained as consequences of open-ocean ecosystem alteration by the mass extinction. If this explanation is correct, the extent and timing of marine biogeochemical recovery from the end-Cretaceous event was ultimately contingent on the extent and timing of open-ocean ecosystem recovery. The biogeochemical recovery may in turn have created new evolutionary opportunities for a diverse array of marine organisms.
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  • 14
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 1-21 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Variation in the subtle differences between right and left sides of bilateral characters, or fluctuating asymmetry (FA), has long been considered to be primarily environmental in origin, and this has promoted its use as a measure of developmental instability (DI) in populations. There is little evidence for specific genes that govern FA per se. Numerous studies show that FA levels in various characters are influenced by dominance and especially epistatic interactions among genes. An epistatic genetic basis for FA may complicate its primary use in comparisons of DI levels in outbred or wild populations subjected or not subjected to various environmental stressors. Although the heritability of FA typically is very low or zero, epistasis can generate additive genetic variation for FA that may allow it to evolve especially in populations subjected to bottlenecks, hybridizations, or periods of rapid environmental changes caused by various stresses.
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  • 15
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 419-444 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Understanding and predicting the dynamics of multispecies systems generally require estimates of interaction strength among species. Measuring interaction strength is difficult because of the large number of interactions in any natural system, long-term feedback, multiple pathways of effects between species pairs, and possible nonlinearities in interaction-strength functions. Presently, the few studies that extensively estimate interaction strength suggest that distributions of interaction strength tend to be skewed toward few strong and many weak interactions. Modeling studies indicate that such skewed patterns tend to promote system stability and arise during assembly of persistent communities. Methods for estimating interaction strength efficiently from traits of organisms, such as allometric relationships, show some promise. Methods for estimating community response to environmental perturbations without an estimate of interaction strength may also be of use. Spatial and temporal scale may affect patterns of interaction strength, but these effects require further investigation and new multispecies modeling frameworks. Future progress will be aided by development of long-term multispecies time series of natural communities, by experimental tests of different methods for estimating interaction strength, and by increased understanding of nonlinear functional forms.
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  • 16
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 643-689 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Oysters have been introduced worldwide to 73 countries, but the ecological consequences of the introductions are not fully understood. Economically, introduced oysters compose a majority of oyster harvests in many areas. Oysters are ecosystem engineers that influence many ecological processes, such as maintenance of biodiversity, population and food web dynamics, and nutrient cycling. Consequently, both their loss, through interaction of overharvest, habitat degradation, disease, poor water quality, and detrimental species interactions, and their gain, through introductions, can cause complex changes in coastal ecosystems. Introductions can greatly enhance oyster population abundance and production, as well as populations of associated native species. However, introduced oysters are also vectors for non-native species, including disease-causing organisms. Thus, substantial population, community, and habitat changes have accompanied new oysters. In contrast, ecosystem-level consequences of oyster introductions, such as impacts on flow patterns, sediment and nutrient dynamics, and native bioengineering species, are not well understood. Ecological risk assessments for future introductions must emphasize probabilities of establishment, spread, and impacts on vulnerable species, communities, and ecosystem properties. Many characteristics of oysters lead to predictions that they would be successful, high-impact members of recipient ecosystems. This conclusion leaves open the discussion of whether such impacts are desirable in terms of restoration of coastal ecosystems, especially where restoration of native oysters is possible.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 219-242 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The multi-gene family that encodes ribosomal RNA (the rDNA) has been the subject of numerous review articles examining its structure and function, as well as its use as a molecular systematic marker. The purpose of this review is to integrate information about structural and functional aspects of rDNA that impact the ecology and evolution of organisms. We examine current understanding of the impact of length heterogeneity and copy number in the rDNA on fitness and the evolutionary ecology of organisms. We also examine the role that elemental ratios (biological stoichiometry) play in mediating the impact of rDNA variation in natural populations and ecosystems. The body of work examined suggests that there are strong reciprocal feedbacks between rDNA and the ecology of all organisms, from microbes to metazoans, mediated through increased phosphorus demand in organisms with high rRNA content.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 23-46 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Two consequences of terrestrial ectothermy (low energy needs and behavioral control of body temperatures) have had major consequences for the evolution of reptile life-history traits. For example, reproducing females can manipulate incubation temperatures and thus phenotypic traits of their offspring by retaining developing eggs in utero. This ability has resulted in multiple evolutionary transitions from oviparity to viviparity in cool-climate reptile populations. The spatial and temporal heterogeneity of operative temperatures in terrestrial habitats also has favored careful nest-site selection and a matching of embryonic reaction norms to thermal regimes during incubation (e.g., via temperature-dependent sex determination). Many of the life-history features in which reptiles differ from endothermic vertebratesĐ??such as their small offspring sizes, large litter sizes, and infrequent reproductionĐ??are direct consequences of ectothermy, reflecting freedom from heat-conserving constraints on body size and energy storage. Ectothermy confers immense flexibility, enabling a dynamic matching of life-history traits to local circumstances. This flexibility has generated massive spatial and temporal variation in life-history traits via phenotypic plasticity as well as adaptation. The diversity of life histories in reptiles can best be interpreted within a conceptual framework that views reptiles as low-energy, variable-temperature systems.
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  • 19
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 541-562 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The continuous flow of genomic data is creating unprecedented opportunities for the reconstruction of molecular phylogenies. Access to whole-genome data means that phylogenetic analysis can now be performed at different genomic levels, such as primary sequences and gene order, allowing for reciprocal corroboration of the results. We critically review the different kinds of phylogenomic methods currently available, paying particular attention to method reliability. Our emphasis is on methods for the analysis of primary sequences because these are the most advanced. We discuss the important issue of statistical inconsistency and show how failing to fully capture the process of sequence evolution in the underlying models leads to tree reconstruction artifacts. We suggest strategies for detecting and potentially overcoming these problems. These strategies involve the development of better models, the use of an improved taxon sampling, and the exclusion of phylogenetically misleading data.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 267-294 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: It has often been argued that conserving biodiversity is necessary for maintaining ecosystem functioning. We critically evaluate the current evidence for this argument. Although there is substantial evidence that diversity is able to affect function, particularly for plant communities, it is unclear if these patterns will hold for realistic scenarios of extinctions, multitrophic communities, or larger spatial scales. Experiments are conducted at small spatial scales, the very scales at which diversity tends to increase owing to exotics. Stressors may affect function by many pathways, and diversity-mediated effects on function may be a minor pathway, except in the case of multiple-stressor insurance effects. In general, the conservation case is stronger for stability measures of function than stock and flux measures, in part because it is easier to attribute value unambiguously to stability and in part because stock and flux measures of functions are anticipated to be more affected by multitrophic dynamics. Nor is biodiversity-ecosystem function theory likely to help conservation managers in practical decisions, except in the particular case of restoration. We give recommendations for increasing the relevance of this area of research for conservation.
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  • 21
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 597-620 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The diversity and composition of herbivore assemblages was a favored theme for community ecology in the 1970s and culminated in 1984 with Insects on Plants by Strong, Lawton and Southwood. We scrutinize findings since then, considering analyses of country-wide insect-host catalogs, field studies of local herbivore communities, and comparative studies at different spatial scales. Studies in tropical forests have advanced significantly and offer new insights into stratification and host specialization of herbivores. Comparative and long-term data sets are still scarce, which limits assessment of general patterns in herbivore richness and assemblage structure. Methods of community phylogenetic analysis, complex networks, spatial and among-host diversity partitioning, and metacommunity models represent promising approaches for future work.
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    Annual Review of Genetics 39 (2005), S. 359-407 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Life is the interplay between structure and energy, yet the role of energy deficiency in human disease has been poorly explored by modern medicine. Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive oxygen species (ROS) as a toxic by-product, I hypothesize that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer. Because mitochondrial DNA (mtDNA) is present in thousands of copies per cell and encodes essential genes for energy production, I propose that the delayed-onset and progressive course of the age-related diseases results from the accumulation of somatic mutations in the mtDNAs of post-mitotic tissues. The tissue-specific manifestations of these diseases may result from the varying energetic roles and needs of the different tissues. The variation in the individual and regional predisposition to degenerative diseases and cancer may result from the interaction of modern dietary caloric intake and ancient mitochondrial genetic polymorphisms. Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbears to energetically adapt to their ancestral homes are influencing our health today.
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    Annual Review of Genetics 39 (2005), S. 69-94 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Cell-cycle control of transcription seems to be a universal feature of proliferating cells, although relatively little is known about its biological significance and conservation between organisms. The two distantly related yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe have provided valuable complementary insight into the regulation of periodic transcription as a function of the cell cycle. More recently, genome-wide studies of proliferating cells have identified hundreds of periodically expressed genes and underlying mechanisms of transcriptional control. This review discusses the regulation of three major transcriptional waves, which roughly coincide with three main cell-cycle transitions (initiation of DNA replication, entry into mitosis, and exit from mitosis). I also compare and contrast the transcriptional regulatory networks between the two yeasts and discuss the evolutionary conservation and possible roles for cell cycle-regulated transcription.
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    Annual Review of Genetics 39 (2005), S. 23-46 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Three processes alter genomic sequence and structure at the immunoglobulin genes of B lymphocytes: gene conversion, somatic hypermutation, and class switch recombination. Though the molecular signatures of these processes differ, they occur by a shared pathway which is induced by targeted DNA deamination by a B cellĐ??specific factor, activation induced cytidine deaminase (AID). Ubiquitous factors critical for DNA repair carry out all downstream steps, creating mutations and deletions in genomic DNA. This review focuses on the genetic and biochemical mechanisms of diversification of immunoglobulin genes.
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    Annual Review of Genetics 39 (2005), S. 561-613 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The basic vertebrate body plan of the zebrafish embryo is established in the first 10 hours of development. This period is characterized by the formation of the anterior-posterior and dorsal-ventral axes, the development of the three germ layers, the specification of organ progenitors, and the complex morphogenetic movements of cells. During the past 10 years a combination of genetic, embryological, and molecular analyses has provided detailed insights into the mechanisms underlying this process. Maternal determinants control the expression of transcription factors and the location of signaling centers that pattern the blastula and gastrula. Bmp, Nodal, FGF, canonical Wnt, and retinoic acid signals generate positional information that leads to the restricted expression of transcription factors that control cell type specification. Noncanonical Wnt signaling is required for the morphogenetic movements during gastrulation. We review how the coordinated interplay of these molecules determines the fate and movement of embryonic cells.
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    Annual Review of Genetics 39 (2005), S. 481-501 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The zebrafish (Danio rerio) has emerged as an ideal organism for the study of hematopoiesis, the process by which all the cellular elements of the blood are formed. These elements, including erythrocytes, granulocytes, monocytes, lymphocytes, and thrombocytes, are formed through complex genetic signaling pathways that are highly conserved throughout phylogeny. Large-scale forward genetic screens have identified numerous blood mutants in zebrafish, helping to elucidate specific signaling pathways important for hematopoietic stem cells (HSCs) and the various committed blood cell lineages. Here we review both primitive and definitive hematopoiesis in zebrafish, discuss various genetic methods available in the zebrafish model for studying hematopoiesis, and describe some of the zebrafish blood mutants identified to date, many of which have known human disease counterparts.
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    Annual Review of Genetics 39 (2005), S. 339-358 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The moss Physcomitrella patens, like seed plants, shows alternation of generations, but its gametophyte, the haploid phase of the life cycle, is dominant, making it ideal for genetic studies. Crosses show direct segregations, so F2 or test crosses are unnecessary. Mutagenesis yields mutants, the phenotype of which is directly evident. Haploid tissue can be propagated vegetatively, allowing the maintenance of mutants blocked early in development. Protoplasts, isolated from filamentous gametophytic tissue, regenerate directly into filamentous tissue, providing an abundant supply of single haploid cells for transformation. Recombination occurs at a high frequency between genomic sequences in transforming DNA and the corresponding chromosomal sequences, allowing precise inactivation or modification of genes. RNAi technology allows the inactivation of the expression of gene families and the partial knockdown of essential genes. Over 100,000 ESTs have been sequenced and annotated, and sequencing of the genome should be completed by the end of 2005.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 319-349 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Progress in experimental and theoretical biology is likely to provide us with the opportunity to assemble detailed predictive models of mammalian cells. Using a functional format to describe the organization of mammalian cells, we describe current approaches for developing qualitative and quantitative models using data from a variety of experimental sources. Recent developments and applications of graph theory to biological networks are reviewed. The use of these qualitative models to identify the topology of regulatory motifs and functional modules is discussed. Cellular homeostasis and plasticity are interpreted within the framework of balance between regulatory motifs and interactions between modules. From this analysis we identify the need for detailed quantitative models on the basis of the representation of the chemistry underlying the cellular process. The use of deterministic, stochastic, and hybrid models to represent cellular processes is reviewed, and an initial integrated approach for the development of large-scale predictive models of a mammalian cell is presented.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 1-33 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: In this review I describe the several stages of my research career, all of which were driven by a desire to understand the basic mechanisms responsible for the complex and beautiful organization of the eukaryotic cell. I was originally trained as an electron microscopist in Argentina, and my first major contribution was the introduction of glutaraldehyde as a fixative that preserved the fine structure of cells, which opened the way for cytochemical studies at the EM level. My subsequent work on membrane-bound ribosomes illuminated the process of cotranslational translocation of polypeptides across the ER membrane and led to the formulation, with Gunter Blobel, of the signal hypothesis. My later studies with many talented colleagues contributed to an understanding of ER structure and function and aspects of the mechanisms that generate and maintain the polarity of epithelial cells. For this work my laboratory introduced the now widely adopted Madin-Darby canine kidney (MDCK) cell line, and demonstrated the polarized budding of envelope viruses from those cells, providing a powerful new system that further advanced the field of protein traffic.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 133-153 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Chromatin can be differentiated by the deposition of variant histones at centromeres, active genes, and silent loci. Variant histones are assembled into nucleosomes in a replication-independent manner, in contrast to assembly of bulk chromatin that is coupled to replication. Recent in vitro studies have provided the first glimpses of protein machines dedicated to building and replacing alternative nucleosomes. They deposit variant H2A and H3 histones and are targeted to particular functional sites in the genome. Differences between variant and canonical histones can have profound consequences, either for delivery of the histones to sites of assembly or for their function after incorporation into chromatin. Recent studies have also revealed connections between assembly of variant nucleosomes, chromatin remodeling, and histone post-translational modification. Taken together, these findings indicate that chromosome architecture can be highly dynamic at the most fundamental level, with epigenetic consequences.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 203-222 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Plants shape their organs with a precision demanded by optimal function; organ shaping requires control over cell wall expansion anisotropy. Focusing on multicellular organs, I survey the occurrence of expansion anisotropy and discuss its causes and proposed controls. Expansion anisotropy of a unit area of cell wall is characterized by the direction and degree of anisotropy. The direction of maximal expansion rate is usually regulated by the direction of net alignment among cellulose microfibrils, which overcomes the prevailing stress anisotropy. In some stems, the directionality of expansion of epidermal cells is controlled by that of the inner tissue. The degree of anisotropy can vary widely as a function of position and of treatment. The degree of anisotropy is probably controlled by factors in addition to the direction of microfibril alignment. I hypothesize that rates of expansion in maximal and minimal directions are regulated by distinct molecular mechanisms that regulate interactions between matrix and microfibrils.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 581-603 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Over the past decades, intravital microscopy (IVM), the imaging of cells in living organisms, has become a valuable tool for studying the molecular determinants of lymphocyte trafficking. Recent advances in microscopy now make it possible to image cell migration and cell-cell interactions in vivo deep within intact tissues. Here, we summarize the principal techniques that are currently used in IVM, discuss options and tools for fluorescence-based visualization of lymphocytes in microvessels and tissues, and describe IVM models used to explore lymphoid and non-lymphoid organs. The latter will be introduced according to the physiologic itinerary of developing and differentiating T and B lymphocytes as they traffic through the body, beginning with their development in bone marrow and thymus and continuing with their migration to secondary lymphoid organs and peripheral tissues.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 411-434 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Centrosomes, spindle pole bodies, and related structures in other organisms are a morphologically diverse group of organelles that share a common ability to nucleate and organize microtubules and are thus referred to as microtubule organizing centers or MTOCs. Features associated with MTOCs include organization of mitotic spindles, formation of primary cilia, progression through cytokinesis, and self-duplication once per cell cycle. Centrosomes bind more than 100 regulatory proteins, whose identities suggest roles in a multitude of cellular functions. In fact, recent work has shown that MTOCs are required for several regulatory functions including cell cycle transitions, cellular responses to stress, and organization of signal transduction pathways. These new liaisons between MTOCs and cellular regulation are the focus of this review. Elucidation of these and other previously unappreciated centrosome functions promises to yield exciting scientific discovery for some time to come.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 695-718 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The combined use of the new technologies of multiphoton-based intravital imaging, the chemotaxis-mediated collection of invasive cells, and high sensitivity expression profiling has allowed the correlation of the behavior of invasive tumor cells in vivo with their gene expression patterns. New insights have resulted including a gene expression signature for invasive cells and the tumor microenvironment invasion model. This model proposes that tumor invasion and metastasis can be studied as a problem resembling normal morphogenesis. We discuss how these new insights may lead to a better understanding of the molecular basis of the invasive behavior of tumor cells in vivo, which may result in new strategies for the diagnosis and treatment of metastasis.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 435-456 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Secretory and transmembrane proteins enter the secretory pathway through the protein-conducting Sec61 channel in the membrane of the endoplasmic reticulum. In the endoplasmic reticulum, proteins fold, are frequently covalently modified, and oligomerize before they are packaged into transport vesicles that shuttle them to the Golgi complex. Proteins that misfold in the endoplasmic reticulum are selectively transported back across the endoplasmic reticulum membrane to the cytosol for degradation by proteasomes. Depending on the topology of the defect in the protein, cytosolic or lumenal chaperones are involved in its targeting to degradation. The export channel for misfolded proteins is likely also formed by Sec61p. Export may be powered by AAA-ATPases of the proteasome 19S regulatory particle or Cdc48p/p97. Exported proteins are frequently ubiquitylated prior to degradation and are escorted to the proteasome by polyubiquitin-binding proteins.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 511-527 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Phagocytosis, the process by which cells engulf large particles, requires a substantial contribution of membranes. Recent studies have revealed that intracellular compartments, including endocytic organelles and the endoplasmic reticulum (ER), can engage in fusion events with the plasma membrane at the sites of nascent phagosomes. The finding that ER proteins are delivered to phagosomes, where degraded peptides are loaded onto major histocompatibility complex (MHC) class II molecules, has significantly enhanced our understanding of the immune functions associated with these organelles. Although it is well known that pathogens are killed in phagosomes, the contribution of ER proteins to phagosomes has provided a novel pathway for the loading of exogenous peptides onto MHC class I molecules, a process known as cross-presentation. Thus, phagocytosis has evolved from a nutritional function in unicellular organisms to play key roles in both innate and adaptive immunity in vertebrates.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 551-580 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The sensory and motor components of nervous systems are connected topographically and contain neural maps of the external world. The paradigm for such maps is the precisely ordered wiring of the output cells of the eye to their synaptic targets in the tectum of the midbrain. The retinotectal map is organized in development through the graded activity of Eph receptor tyrosine kinases and their ephrin ligands. These signaling proteins are arrayed in complementary expression gradients along the orthogonal axes of the retina and tectum, and provide both input and recipient cells with Cartesian coordinates that specify their location. Molecular genetic studies in the mouse indicate that these coordinates are interpreted in the context of neuronal competition for termination sites in the tectum. They further suggest that order in the retinotectal map is determined by ratiometric rather than absolute difference comparisons in Eph signaling along the temporal-nasal and dorsal-ventral axes of the eye.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 271-295 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The cytoskeleton plays important roles in plant cell shape determination by influencing the patterns in which cell wall materials are deposited. Cortical microtubules are thought to orient the direction of cell expansion primarily via their influence on the deposition of cellulose into the wall, although the precise nature of the microtubule-cellulose relationship remains unclear. In both tip-growing and diffusely growing cell types, F-actin promotes growth and also contributes to the spatial regulation of growth. F-actin has been proposed to play a variety of roles in the regulation of secretion in expanding cells, but its functions in cell growth control are not well understood. Recent work highlighted in this review on the morphogenesis of selected cell types has yielded substantial new insights into mechanisms governing the dynamics and organization of cytoskeletal filaments in expanding plant cells and how microtubules and F-actin interact to direct patterns of cell growth. Nevertheless, many important questions remain to be answered.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 485-509 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The establishment of the Angiosperm root apical meristem is dependent on the specification of a stem cell niche and the subsequent development of the quiescent center at the presumptive root pole. Distribution of auxin and the establishment of auxin maxima are early formative steps in niche specification that depend on the expression and distribution of auxin carriers. Auxin specifies stem cell niche formation by directly and indirectly affecting gene activities. Part of the indirect regulation by auxin may involve changes in redox, favoring local, oxidized microenvironments. Formation of a QC is required for root meristem development and elaboration. Many signals likely pass between the QC and the adjacent root meristem tissues. Disappearance of the QC is associated with roots becoming determinate. Given the many auxin feedback loops, we hypothesize that roots evolved as part of an auxin homeostasis mechanism.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 155-176 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Polarization is a feature common to many cell types. Epithelial cells, for example, exhibit a characteristic apical-basolateral polarity that is critical for their function. In addition to this ubiquitous form of polarity, whole fields of cells are often polarized in a plane perpendicular to the apical-basal axis. This form of polarity, referred to as planar cell polarity (PCP), exists in all adult Drosophila cuticular tissues, as well as in numerous vertebrate tissues, including the mammalian skin and inner ear epithelia. Recent advances in the study of PCP establishment are beginning to unravel the molecular mechanisms underlying this cellular process. This review discusses new developments in the molecular understanding of PCP in Drosophila and vertebrates and integrates the current data in a model to illustrate how interactions between PCP factors might function to generate planar polarity.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 125-146 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: In contrast to Bateman's principle, there is now increasing evidence that female fitness can depend on the number of mates obtained. A number of genetic benefits have been proposed for the evolution of polyandry. A meta-analysis of available data suggests that polyandry, rather than multiple mating, can have a weak but significant general effect on embryo viability, as indicated by egg hatching success. Although this effect is generally regarded as evidence in favor of the genetic incompatibility hypothesis, appropriate data that test for intrinsic sire effects on embryo viability are generally unavailable. Moreover, maternal effects that could generate the result have not been adequately controlled, and there is little unequivocal evidence to suggest that fertilization is biased toward sperm bearing genotypes that would enhance offspring viability. Greater effort is required in these areas to elucidate the mechanisms underlying observed fitness effects of polyandry.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 621-642 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The reconstruction of evolutionary trees from mitochondrial DNA (mtDNA) data is a common tool with which to infer the relationships of living organisms. The wide use of mtDNA stems from the ease of getting new sequence data for a set of orthologus genes and from the availability of many existing mtDNA sequences for a wide array of species. In this review we argue that developing a fuller understanding of the biology of mitochondria is essential for the rigorous application of mtDNA to inferences about the evolutionary history of species or populations. Though much progress has been made in understanding the parameters that shape the evolution of mitochondria and mtDNA, many questions still remain, and a better understanding of the role this organelle plays in regulating organismal fitness is becoming increasingly critical for accurate phylogeny reconstruction. In population biology, the limited information content of one nonrecombining genetic marker can compromise evolutionary inference, and the effects of nuclear genetic variationĐ??and environmental factorsĐ??in mtDNA fitness differences can compound these problems. In systematics, the limited gene set, biased amino acid composition, and problems of compensatory substitutions can cloud phylogenetic signal. Dissecting the functional bases of these biases offers both challenges and opportunities in comparative biology.
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    Notes: Quantifying the extent to which seed production is limited by the availability of pollen has been an area of intensive empirical study over the past few decades. Whereas theory predicts that pollen augmentation should not increase seed production, numerous empirical studies report significant and strong pollen limitation. Here, we use a variety of approaches to examine the correlates of pollen limitation in an effort to understand its occurrence and importance in plant evolutionary ecology. In particular, we examine the role of recent ecological perturbations in influencing pollen limitation and discuss the relation between pollen limitation and plant traits. We find that the magnitude of pollen limitation observed in natural populations depends on both historical constraints and contemporary ecological factors.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 147-168 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Individual-based models (IBMs) allow the explicit inclusion of individual variation in greater detail than do classical differential-equation and difference-equation models. Inclusion of such variation is important for continued progress in ecological and evolutionary theory. We provide a conceptual basis for IBMs by describing five major types of individual variation in IBMs: spatial, ontogenetic, phenotypic, cognitive, and genetic. IBMs are now used in almost all subfields of ecology and evolutionary biology. We map those subfields and look more closely at selected key papers on fish recruitment, forest dynamics, sympatric speciation, metapopulation dynamics, maintenance of diversity, and species conservation. Theorists are currently divided on whether IBMs represent only a practical tool for extending classical theory to more complex situations, or whether individual-based theory represents a radically new research program. We feel that the tension between these two poles of thinking can be a source of creativity in ecology and evolutionary theory.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 373-397 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Immune responses can cause severe disease, despite the role immunity plays in defending against parasitism. Indeed, immunopathology is a remarkably common cause of disease and has strong impacts upon both host and parasite fitness. Why has immune-mediated disease not been eliminated by natural selection? What constraints might immunopathology impose upon the evolution of resistance? In this review, we explore two major mechanistic causes of immunopathology in mammals and consider how such disease may have influenced immune system design. We then propose hypotheses that could explain the failure of natural selection to eliminate immunopathology. Finally, we suggest how the evolution of strategies for parasite virulence and host resistance may be shaped by this "double-edged sword" of immunity. Future work may reveal whether immunopathology constrains the evolution of resistance in all host taxa.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 243-266 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Plant adaptation to serpentine soil has been a topic of study for many decades, yet investigation of the genetic component of this adaptation has only recently begun. We review the defining properties of serpentine soil and the pioneering work leading to three established physiological and evolutionary mechanisms hypothesized to be responsible for serpentine tolerance: tolerance of a low calcium-to-magnesium ratio, avoidance of Mg toxicity, or a high Mg requirement. In addition, we review recent work in serpentine ecology documenting the high proportion of endemic species present, the adaptive morphologies of serpentine-tolerant plants, and the distinctive structure of serpentine communities. Studies of the physiological mechanisms proposed to confer serpentine tolerance have shown that uptake of particular ions and heavy metals varies between serpentine-tolerant and -intolerant species. Recent studies examining the genetic basis of serpentine adaptation have shown serpentine-adaptive quantitative trait loci (QTL) to have large phenotypic effects, drought tolerance to be as important as metal tolerance, and serpentine adaptation to have evolved independently multiple times within species. Investigations of plant races and species adapted to contrasting soil types have shown disparate flowering times, divergent floral morphologies, and pollen incompatibility to contribute to reproductive isolation. Finally, we propose that future studies involving serpentine systems should merge the fields of ecology, evolution, physiology, and genetics.
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    Annual Review of Genetics 39 (2005), S. 537-559 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Ciliated protozoan are unicellular eukaryotes. Most species in this diverse group display nuclear dualism, a special feature that supports both somatic and germline nuclei in the same cell. Probably due to this unique life style, they exhibit unusual nuclear characteristics that have intrigued researchers for decades. Among them are large-scale DNA rearrangements, which restructure the somatic genome to become drastically different from its germline origin. They resemble the classical phenomenon of chromatin diminution in some nematodes discovered more than a century ago. The mechanisms of such rearrangements, their biological roles, and their evolutionary origins have been difficult to understand. Recent studies have revealed a clear link to RNA interference, and begin to shed light on these issues. Using the simple ciliate Tetrahymena as a model, this chapter summarizes the physical characterization of these processes, describes recent findings that connect them to RNA interference, and discusses the details of their mechanisms, potential roles in genome defense, and possible occurrences in other organisms.
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    Annual Review of Genetics 39 (2005), S. 503-536 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Mitochondria form dynamic tubular networks that continually change their shape and move throughout the cell. In eukaryotes, these organellar gymnastics are controlled by numerous pathways that preserve proper mitochondrial morphology and function. The best understood of these are the fusion and fission pathways, which rely on conserved GTPases and their binding partners to regulate organelle connectivity and copy number in healthy cells and during apoptosis. In budding yeast, mitochondrial shape is also maintained by proteins acting in the tubulation pathway. Novel proteins and pathways that control mitochondrial dynamics continue to be discovered, indicating that the mechanisms governing this organelle's behavior are more sophisticated than previously appreciated. Here we review recent advances in the field of mitochondrial dynamics and highlight the importance of these pathways to human health.
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    Annual Review of Genetics 39 (2005), S. 173-195 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Germline stem cells (GSCs), which can self-renew and generate differentiated progeny, are unique stem cells in that they are solely dedicated to reproduction and transmit genetic information from generation to generation. Through the use of genetic techniques in Drosophila, Caenorhabditis elegans, and mouse, exciting progress has been made in understanding molecular mechanisms underlying interactions between stem cells and niches. The knowledge gained from studying GSCs has provided an intellectual framework for defining niches and molecular regulatory mechanisms for other adult stem cells. In this review, we summarize recent progress and discuss conserved mechanisms underlying GSC self-renewal and differentiation by comparing three GSC systems. Because GSCs and other adult stem cells share "stemness," we hope this review will help define fundamental principles of stem cell regulation and provide further guidance for future studies of other adult stem cells.
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    Annual Review of Genetics 39 (2005), S. 431-451 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Nonhomologous end joining (NHEJ), the direct rejoining of DNA double-strand breaks, is closely associated with illegitimate recombination and chromosomal rearrangement. This has led to the concept that NHEJ is error prone. Studies with the yeast Saccharomyces cerevisiae have revealed that this model eukaryote has a classical NHEJ pathway dependent on Ku and DNA ligase IV, as well as alternative mechanisms for break rejoining. The evolutionary conservation of the Ku-dependent process includes several genes dedicated to this pathway, indicating that classical NHEJ at least is a strong contributor to fitness in the wild. Here we review how double-strand break structure, the yeast NHEJ proteins, and alternative rejoining mechanisms influence the accuracy of break repair. We also consider how the balance between NHEJ and homologous repair is regulated by cell state to promote genome preservation. The principles discussed are instructive to NHEJ in all organisms.
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    Annual Review of Genetics 39 (2005), S. 47-68 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Bacillus subtilis uses novel regulatory mechanisms in controlling expression of its genes of tryptophan synthesis and transport. These mechanisms respond to changes in the intracellular concentrations of free tryptophan and uncharged tRNATrp. The major B. subtilis protein that regulates tryptophan biosynthesis is the tryptophan-activated RNA-binding attenuation protein, TRAP. TRAP is a ring-shaped molecule composed of 11 identical subunits. Active TRAP binds to unique RNA segments containing multiple trinucleotide (NAG) repeats. Binding regulates both transcription termination and translation in the trp operon, and translation of other coding regions relevant to tryptophan metabolism. When there is a deficiency of charged tRNATrp, B. subtilis forms an anti-TRAP protein, AT. AT antagonizes TRAP function, thereby increasing expression of all the genes regulated by TRAP. Thus B. subtilis and Escherichia coli respond to identical regulatory signals, tryptophan and uncharged tRNATrp, yet they employ different mechanisms in regulating trp gene expression.
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    Annual Review of Genetics 39 (2005), S. 95-119 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The arthropods display a wide range of morphological diversity, varying tagmosis, as well as other aspects of the body plan, such as appendage and cuticular morphology. Here we review the roles of developmental regulatory genes in the evolution of arthropod morphology, with an emphasis on what is known from morphologically diverse species. Examination of tagmatic evolution reveals that these changes have been accompanied by changes in the expression patterns of Hox genes. In contrast, review of the modifications to wing morphology seen in insects shows that these body plan changes have generally favored alterations in downstream target genes. These and other examples are used to discuss the evolutionary implications of comparative developmental genetic data.
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    Notes: Recent advancements in single-molecule tracking methods with nanometer-level precision now allow researchers to observe the movement, recruitment, and activation of single molecules in the plasma membrane in living cells. In particular, on the basis of the observations by high-speed single-particle tracking at a frame rate of 40,000 frames s1, the partitioning of the fluid plasma membrane into submicron compartments throughout the cell membrane and the hop diffusion of virtually all the molecules have been proposed. This could explain why the diffusion coefficients in the plasma membrane are considerably smaller than those in artificial membranes, and why the diffusion coefficient is reduced upon molecular complex formation (oligomerization-induced trapping). In this review, we first describe the high-speed single-molecule tracking methods, and then we critically review a new model of a partitioned fluid plasma membrane and the involvement of the actin-based membrane-skeleton "fences" and anchored-transmembrane protein "pickets" in the formation of compartment boundaries.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 1-20 
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 201-219 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: The recent development of new techniques to manipulate single DNA molecules has opened new opportunities for the study of the enzymes that control DNA topology: the type I and II topoisomerases. These single-molecule assays provide a unique way to study the uncoiling of single supercoiled DNA molecules and the unlinking of two intertwined DNAs. They allow for a detailed characterization of the activity of topoisomerases, including the processivity, the chiral discrimination, and the dependence of their enzymatic rate on ATP concentration, degree of supercoiling, and the tension in the molecule. These results shed new light on the mechanism of these enzymes and their function in vivo.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 43-69 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Simulation of protein folding has come a long way in five years. Notably, new quantitative comparisons with experiments for small, rapidly folding proteins have become possible. As the only way to validate simulation methodology, this achievement marks a significant advance. Here, we detail these recent achievements and ask whether simulations have indeed rendered quantitative predictions in several areas, including protein folding kinetics, thermodynamics, and physics-based methods for structure prediction. We conclude by looking to the future of such comparisons between simulations and experiments.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 119-151 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Research in the past decade has revealed that many cytosolic proteins are recruited to different cellular membranes to form protein-protein and lipid-protein interactions during cell signaling and membrane trafficking. Membrane recruitment of these peripheral proteins is mediated by a growing number of modular membrane-targeting domains, including C1, C2, PH, FYVE, PX, ENTH, ANTH, BAR, FERM, and tubby domains, that recognize specific lipid molecules in the membranes. Structural studies of these membrane-targeting domains demonstrate how they specifically recognize their cognate lipid ligands. However, the mechanisms by which these domains and their host proteins are recruited to and interact with various cell membranes are only beginning to unravel with recent computational studies, in vitro membrane binding studies using model membranes, and cellular translocation studies using fluorescent protein-tagged proteins. This review summarizes the recent progress in our understanding of how the kinetics and energetics of membrane-protein interactions are regulated during the cellular membrane targeting and activation of peripheral proteins.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 633-657 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: In contrast to other tissues, the nervous system is enriched in the polyunsaturated fatty acids (PUFAs): arachidonic acid (AA, 20:4 n-6) and docosahexaenoic acid (DHA, 22:6 n-3). Despite their abundance in the nervous system, AA and DHA cannot be synthesized de novo by mammals; they, or their precursors, must be ingested from dietary sources and transported to the brain. During late gestation and the early postnatal period, neurodevelopment is exceptionally rapid, and substantial amounts of PUFAs, especially DHA, are critical to ensure neurite outgrowth as well as proper brain and retina development. Here, we review the various functions of DHA in the nervous system, the proteins involved in its internalization and metabolism into phospholipids, and its relationship to several neurological disorders, including Alzheimer's disease and depression.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 319-346 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Bacteria communicate with one another using chemical signal molecules. As in higher organisms, the information supplied by these molecules is critical for synchronizing the activities of large groups of cells. In bacteria, chemical communication involves producing, releasing, detecting, and responding to small hormone-like molecules termed autoinducers . This process, termed quorum sensing, allows bacteria to monitor the environment for other bacteria and to alter behavior on a population-wide scale in response to changes in the number and/or species present in a community. Most quorum-sensing-controlled processes are unproductive when undertaken by an individual bacterium acting alone but become beneficial when carried out simultaneously by a large number of cells. Thus, quorum sensing confuses the distinction between prokaryotes and eukaryotes because it enables bacteria to act as multicellular organisms. This review focuses on the architectures of bacterial chemical communication networks; how chemical information is integrated, processed, and transduced to control gene expression; how intra- and interspecies cell-cell communication is accomplished; and the intriguing possibility of prokaryote-eukaryote cross-communication.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 177-201 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Brassinosteroids (BRs), the polyhydroxylated steroid hormones of plants, regulate the growth and differentiation of plants throughout their life cycle. Over the past several years, genetic and biochemical approaches have yielded great progress in understanding BR signaling. Unlike their animal counterparts, BRs are perceived at the plasma membrane by direct binding to the extracellular domain of the BRI1 receptor S/T kinase. BR perception initiates a signaling cascade, acting through a GSK3 kinase, BIN2, and the BSU1 phosphatase, which in turn modulates the phosphorylation state and stability of the nuclear transcription factors BES1 and BZR1. Microarray technology has been used extensively to provide a global view of BR genomic effects, as well as a specific set of target genes for BES1 and BZR1. These gene products thus provide a framework for how BRs regulate the growth of plants.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 381-410 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: ʼ̛?‚ heterodimeric integrins mediate dynamic adhesive cell-cell and cell-extracellular matrix (ECM) interactions in metazoa that are critical in growth and development, hemostasis, and host defense. A central feature of these receptors is their capacity to change rapidly and reversibly their adhesive functions by modulating their ligand-binding affinity. This is normally achieved through interactions of the short cytoplasmic integrin tails with intracellular proteins, which trigger restructuring of the ligand-binding site through long-range conformational changes in the ectodomain. Ligand binding in turn elicits conformational changes that are transmitted back to the cell to regulate diverse responses. The publication of the integrin ʼ̛V?‚3 crystal structure has provided the context for interpreting decades-old biochemical studies. Newer NMR, crystallographic, and EM data, reviewed here, are providing a better picture of the dynamic integrin structure and the allosteric changes that guide its diverse functions.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 105-131 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: This review surveys what is known about the structure and function of the subnuclear domains called Cajal bodies (CBs). The major focus is on CBs in mammalian cells but we provide an overview of homologous CB structures in other organisms. We discuss the protein and RNA components of CBs, including factors recently found to associate in a cell cycle-dependent fashion or under specific metabolic or stress conditions. We also consider the dynamic properties of both CBs and their molecular components, based largely on recent data obtained thanks to the advent of improved in vivo detection and imaging methods. We discuss how these data contribute to an understanding of CB functions and highlight major questions that remain to be answered. Finally, we consider the interesting links that have emerged between CBs and alterations in nuclear structure apparent in a range of human pathologies, including cancer and inherited neurodegenerative diseases. We speculate on the relationship between CB function and molecular disease.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 57-79 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Phosphoinositide phosphates (PIPs) correspond to phosphorylated derivatives of phosphatidylinositol (PI). Despite their relatively low abundance in the plasma membrane, PIPs play a crucial role as precursors of second messengers and are themselves important signaling and targeting molecules. Indeed, modulation of levels of PIPs affects, for example, cortical actin organization, membrane dynamics, and cell migration. The focus of this review is on selected interesting targets of PIPs. Those proteins that bind PIPs and are involved in regulation of actin assembly, actin membrane linkage, and actin contractility are discussed, as well as those that are involved in signaling, such as small GTPases, protein kinases, and phosphatases, or in regulation of membrane dynamics.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 223-245 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: In eukaryotes, the entwined pathways of RNA transport and local translational regulation are key determinants in the spatio-temporal articulation of gene expression. One of the main advantages of this mechanism over transcriptional control in the nucleus lies in the fact that it endows local sites with independent decision-making authority, a consideration that is of particular relevance in cells with complex cellular architecture such as neurons. Localized RNAs typically contain codes, expressed within cis-acting elements, that specify subcellular targeting. Such codes are recognized by trans-acting factors, adaptors that mediate translocation along cytoskeletal elements by molecular motors. Most transported mRNAs are assumed translationally dormant while en route. In some cell types, especially in neurons, it is considered crucial that translation remains repressed after arrival at the destination site (e.g., a postsynaptic microdomain) until an appropriate activation signal is received. Several candidate mechanisms have been suggested to participate in the local implementation of translational repression and activation, and such mechanisms may target translation at the level of initiation and/or elongation. Recent data indicate that untranslated RNAs may play important roles in the local control of translation.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 519-539 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Niche conservatism is the tendency of species to retain ancestral ecological characteristics. In the recent literature, a debate has emerged as to whether niches are conserved. We suggest that simply testing whether niches are conserved is not by itself particularly helpful or interesting and that a more useful focus is on the patterns that niche conservatism may (or may not) create. We focus specifically on how niche conservatism in climatic tolerances may limit geographic range expansion and how this one type of niche conservatism may be important in (a) allopatric speciation, (b) historical biogeography, (c) patterns of species richness, (d) community structure, (e) the spread of invasive, human-introduced species, (f) responses of species to global climate change, and (g) human history, from 13,000 years ago to the present. We describe how these effects of niche conservatism can be examined with new tools for ecological niche modeling.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 499-518 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Cooperation is common across nonhuman animal taxa, from the hunting of large game in lions to the harvesting of building materials in ants. Theorists have proposed a number of models to explain the evolution of cooperative behavior. These ultimate explanations, however, rarely consider the proximate constraints on the implementation of cooperative behavior. Here we review several types of cooperation and propose a suite of cognitive abilities required for each type to evolve. We propose that several types of cooperation, though theoretically possible and functionally adaptive, have not evolved in some animal species because of cognitive constraints. We argue, therefore, that future modeling efforts and experimental investigations into the adaptive function of cooperation in animals must be grounded in a realistic assessment of the psychological ingredients required for cooperation. Such an approach can account for the puzzling distribution of cooperative behaviors across taxa, especially the seemingly unique occurrence of cooperation observed in our own species.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 345-372 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Aphids and ants are two abundant and highly successful insect groups, which often live in the same habitat and therefore are likely to interact with one another. Whether the outcome of such an interaction is a predator-prey or mutualistic one is dependent on what each partner has to offer relative to the needs of the other. Consequently, understanding why some aphids enter mutualistic interactions with ants is dependent on understanding the physiological, ecological, and evolutionary traits of both partners. This includes an appreciation of the spatial, temporal, and taxonomic context in which mutualistic interactions developed. In this review, we use aphid-ant interactions to illustrate the whole range of interactions from antagonistic to mutualistic as well as to identify the processes affecting the degree of association and in particular the context within which such interactions evolved. The constraints of establishing and maintaining beneficial interactions between aphids and ants is addressed from a cost-benefit perspective. Prospects for future research are identified to further the understanding of the patterns and processes associated with aphid-ant relationships.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 563-595 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Agriculture has evolved independently in three insect orders: once in ants, once in termites, and seven times in ambrosia beetles. Although these insect farmers are in some ways quite different from each other, in many more ways they are remarkably similar, suggesting convergent evolution. All propagate their cultivars as clonal monocultures within their nests and, in most cases, clonally across many farmer generations as well. Long-term clonal monoculture presents special problems for disease control, but insect farmers have evolved a combination of strategies to manage crop diseases: They (a) sequester their gardens from the environment; (b) monitor gardens intensively, controlling pathogens early in disease outbreaks; (c) occasionally access population-level reservoirs of genetically variable cultivars, even while propagating clonal monocultures across many farmer generations; and (d) manage, in addition to the primary cultivars, an array of "auxiliary" microbes providing disease suppression and other services. Rather than growing a single cultivar solely for nutrition, insect farmers appear to cultivate, and possibly "artificially select" for, integrated crop-microbe consortia. Indeed, crop domestication in the context of coevolving and codomesticated microbial consortia may explain the 50-million year old agricultural success of insect farmers.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 399-417 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Most metazoans engage in recombination every generation. In theory this is associated with considerable cost, such as the production of males, so that asexual organisms, which do not pay this cost, should be able to invade populations of sexuals. Some asexuals depend on sperm of sexual males to trigger embryogenesis, a reproductive mode called gynogenesis. The genetic information of males is typically not used. Theory predicts that such mating complexes are short-lived and highly unstable. Sperm dependency is not only the defining feature of the biology of gynogenetic metazoans, it is also a major puzzle in evolutionary biology. Organisms that apparently combine disadvantages of both sexuality and asexuality are a serious challenge to theory. A number of questions about these systems are still unresolved.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 107-124 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The predominantly wind-pollinated order Poales includes about one third of all monocot (Angiosperm) species, with c. 20,000 species dominating modern savanna and steppe vegetation. Recent improvements in understanding relationships within the order allow phylogenetic optimizations of habitat preferences and adaptive character states, enabling exploration of the factors that have influenced evolution in this successful order. Poales probably originated in the late Cretaceous in wet nutrientĐ??poor sunny habitats. By the Paleogene the lineage had diversified into swamps, the forest understory, epiphytic habitats, and nutrient-poor heathlands. The Neogene saw major diversifications of the grasses and possibly the sedges into fire-adapted vegetation in seasonal climates and low atmospheric CO2. Diversification into these habitats was facilitated by morphological features such as the sympodial habit and physiological factors that allowed frequent evolution of CO2-concentrating mechanisms.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 319-344 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Landscape ecology focuses on the reciprocal interactions between spatial pattern and ecological processes, and it is well integrated with ecology. The field has grown rapidly over the past 15 years. The persistent influence of land-use history and natural disturbance on contemporary ecosystems has become apparent. Development of pattern metrics has largely stabilized, and they are widely used to relate landscape pattern to ecological responses. Analyses conducted at multiple scales have demonstrated the importance of landscape pattern for many taxa, and spatially mediated interspecific interactions are receiving increased attention. Disturbance remains prominent in landscape studies, and current research is addressing disturbance interactions. Integration of ecosystem and landscape ecology remains challenging but should enhance understanding of landscape function. Landscape ecology should continue to refine knowledge of when spatial heterogeneity is fundamentally important, rigorously test the generality of its concepts, and develop a more mechanistic understanding of the relationships between pattern and process.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 81-105 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Although predation has a lethal effect on prey, mature terrestrial plants are rarely killed by herbivores, but herbivory can change plant allelochemistry, cell structure and growth, physiology, morphology, and phenology. This review explores the herbivore-induced indirect effects mediated by such plant responses following herbivory in terrestrial systems. Herbivore-induced indirect effects are ubiquitous in many plantĐ??herbivore systems, and indirect interactions occur among temporally separated, spatially separated, and taxonomically distinct herbivore species. Unlike interspecific competition, herbivores can benefit each other through plant-mediated indirect effects. Herbivore-induced changes in plants occur at low levels of herbivory, which increases the likelihood of plant-mediated indirect interactions between herbivores. The herbivore-induced indirect effects result in interaction linkages, which alter species richness and abundance in arthropod communities. Such interaction linkages should be depicted using indirect interaction webs, which incorporate nontrophic, indirect links. The idea of interaction linkages by herbivore-induced indirect effects that shape community organization and biodiversity is an important revision of the traditional view of plant-based terrestrial food webs.
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    Annual Review of Genetics 39 (2005), S. 197-218 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: There is an increasing interest in detecting genes, or genomic regions, that have been targeted by natural selection. The interest stems from a basic desire to learn more about evolutionary processes in humans and other organisms, and from the realization that inferences regarding selection may provide important functional information. This review provides a nonmathematical description of the issues involved in detecting selection from DNA sequences and SNP data and is intended for readers who are not familiar with population genetic theory. Particular attention is placed on issues relating to the analysis of large-scale genomic data sets.
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    Annual Review of Genetics 39 (2005), S. 263-291 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Species of the genus Drosophila exhibit enormous variation in all of their reproductive behaviors: resource use and specialization, courtship signaling, sperm utilization, and female remating. The genetic bases of this variability and its evolution are poorly understood. At the same time, Drosophila comparative genomics now has developed to a point at which approaches previously only possible with D. melanogaster can be exploited to address these questions. We have taken advantage of the known phylogenetic relationships of this group of flies not only to place these behaviors in an evolutionary framework, but to provide a roadmap for future genetic studies.
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    Annual Review of Genetics 39 (2005), S. 409-429 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The lysis-lysogeny decision of bacteriophage lambda (??) is a paradigm for developmental genetic networks. There are three key features, which characterize the network. First, after infection of the host bacterium, a decision between lytic or lysogenic development is made that is dependent upon environmental signals and the number of infecting phages per cell. Second, the lysogenic prophage state is very stable. Third, the prophage enters lytic development in response to DNA-damaging agents. The CI and Cro regulators define the lysogenic and lytic states, respectively, as a bistable genetic switch. Whereas CI maintains a stable lysogenic state, recent studies indicate that Cro sets the lytic course not by directly blocking CI expression but indirectly by lowering levels of CII which activates cI transcription. We discuss how a relatively simple phage like ?? employs a complex genetic network in decision-making processes, providing a challenge for theoretical modeling.
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    Annual Review of Genetics 39 (2005), S. 309-338 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Orthologs and paralogs are two fundamentally different types of homologous genes that evolved, respectively, by vertical descent from a single ancestral gene and by duplication. Orthology and paralogy are key concepts of evolutionary genomics. A clear distinction between orthologs and paralogs is critical for the construction of a robust evolutionary classification of genes and reliable functional annotation of newly sequenced genomes. Genome comparisons show that orthologous relationships with genes from taxonomically distant species can be established for the majority of the genes from each sequenced genome. This review examines in depth the definitions and subtypes of orthologs and paralogs, outlines the principal methodological approaches employed for identification of orthology and paralogy, and considers evolutionary and functional implications of these concepts.
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    Annual Review of Genetics 39 (2005), S. 1-8 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: John Maynard Smith was one of the most original thinkers in evolutionary biology of the post neo-Darwinian synthesis age. He was able to define new problems with clarity and by doing so open up new research directions. He did this in a number of areas including game theory and evolution, the evolution of sex, animal behavior, evolutionary transitions and molecular evolution. Although he is best known for his research and his ideas, he was a great expositor and wrote many books, including introductory texts in the areas of evolution and genetics, ecology and mathematical modeling, as well as advanced expositions of research problems.
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    Annual Review of Genetics 39 (2005), S. 453-479 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Bacterial plasmids encode partitioning (par) loci that ensure ordered plasmid segregation prior to cell division. par loci come in two types: those that encode actin-like ATPases and those that encode deviant Walker-type ATPases. ParM, the actin-like ATPase of plasmid R1, forms dynamic filaments that segregate plasmids paired at mid-cell to daughter cells. Like microtubules, ParM filaments exhibit dynamic instability (i.e., catastrophic decay) whose regulation is an important component of the DNA segregation process. The Walker box ParA ATPases are related to MinD and form highly dynamic, oscillating filaments that are required for the subcellular movement and positioning of plasmids. The role of the observed ATPase oscillation is not yet understood. However, we propose a simple model that couples plasmid segregation to ParA oscillation. The model is consistent with the observed movement and localization patterns of plasmid foci and does not require the involvement of plasmid-specific host-encoded factors.
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    Annual Review of Genetics 39 (2005), S. 153-171 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Among many achievements in the neurodegeneration field in the past decade, two require special attention due to the huge impact on our understanding of molecular and cellular pathogenesis of human neurodegenerative diseases. First is defining specific mutations in familial neurodegenerative diseases and second is modeling these diseases in easily manipulable model organisms including the fruit fly, nematode, and yeast. The power of these genetic systems has revealed many genetic factors involved in the various pathways affected, as well as provided potential drug targets for therapeutics. This review focuses on fruit fly models of human neurodegenerative diseases, with emphasis on how fly models have provided new insights into various aspects of human diseases.
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    Annual Review of Genetics 39 (2005), S. 9-22 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The zebrafish is an excellent model system for studying the molecular basis of inner ear development and function. The eggs develop ex utero and the ear is transparent for the first few weeks of life. Forward genetic screens and antisense technology have helped to elucidate the signaling pathways and molecules required for inner ear development and function. This review addresses the most recent advances in our understanding of how the ear forms and discusses the molecules in hair cells that are essential for sensing sound and movement in the zebrafish.
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    Annual Review of Genetics 39 (2005), S. 219-239 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The myriad developmental roles served by the T-box family of transcription factor genes defy easy categorization. Present in all metazoans, the T-box genes are involved in early embryonic cell fate decisions, regulation of the development of extraembryonic structures, embryonic patterning, and many aspects of organogenesis. They are unusual in displaying dosage sensitivity in most instances. In humans, mutations in T-box genes are responsible for developmental dysmorphic syndromes, and several T-box genes have been implicated in neoplastic processes. T-box transcription factors function in many different signaling pathways, notably bone morphogenetic protein and fibroblast growth factor pathways. The few downstream target genes that have been identified indicate a wide range of downstream effectors.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 245-266 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: The conformation of the ligand in complex with a macromolecular target can be studied by nuclear magnetic resonance (NMR) in solution for both tightly and weakly forming complexes. In the weak binding regime (koff 〉 104 Hz), the structure of the bound ligand is accessible also for very large complexes (〉100 kDa), which are not amenable to NMR studies in the tight binding regime. Here I review the state-of-the-art NMR methodology used for screening ligands and for the structural investigation of bound ligand conformations, in both tight and weak binding regimes. The advantages and disadvantages of each approach are critically described. The NMR methodology used to investigate transiently forming complexes has expanded considerably in the past few years, opening new possibilities for a detailed description of ligand-target interactions. Novel methods for the determination of the bound ligand conformation, in particular transferred cross-correlated relaxation, are thoroughly reviewed, and their advantages with respect to established methodology are discussed, using the epothilone-tubulin complex as a primary example.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 221-243 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: The problem of how ions influence the folding of RNA into specific tertiary structures is being addressed from both thermodynamic (by how much do different salts affect the free energy change of folding) and structural (how are ions arranged on or near an RNA and what kinds of environments do they occupy) points of view. The challenge is to link these different approaches in a theoretical framework that relates the energetics of ion-RNA interactions to the spatial distribution of ions. This review distinguishes three different kinds of ion environments that differ in the extent of direct ion-RNA contacts and the degree to which the ion hydration is perturbed, and summarizes the current understanding of the way each environment relates to the overall energetics of RNA folding.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 21-42 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Molecular interactions are the language that molecules use to communicate recognition, binding, and regulation, events central to biological control mechanisms. Traditionally, such interactions involve direct, atom-to-atom, noncovalent contacts, or indirect contacts bridged by relatively fixed solvent molecules. Here we discuss a third class of molecular communication that, to date, has received less experimental attention, namely solvent-mediated communication between noncontacting macromolecules. This form of communication can be understood in terms of fundamental, well-established principles (coupled equilibria and linkage thermodynamics) that govern interactions between individual polymers and their solutions. In contrast to simple solutions used in laboratory studies, biological systems contain a multitude of nominally noninteracting biopolymers within the same solution environment. The exquisite control of biological function requires some form of communication between many of these solution components, even in the absence of direct and/or indirect contacts. Such communication must be considered when describing potential mechanisms of biological regulation.
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    Annual Review of Biophysics and Biomolecular Structure 34 (2005), S. 71-90 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Despite the central importance of peripheral membrane proteins to cellular signaling and metabolic pathways, the structures of protein-membrane interfaces remain largely inaccessible to high-resolution structural methods. In recent years a number of laboratories have contributed to the development of an electron paramagnetic resonance (EPR) power saturation approach that utilizes site-directed spin labeling to determine the key geometric parameters of membrane-docked proteins, including their penetration depths and angular orientations relative to the membrane surface. Representative applications to Ca2+-activated, membrane-docking C2 domains are described.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 247-269 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Approximately one percent of the human genome encodes proteins that either regulate or are regulated by direct interaction with members of the Rho family of small GTPases. Through a series of complex biochemical networks, these highly conserved molecular switches control some of the most fundamental processes of cell biology common to all eukaryotes, including morphogenesis, polarity, movement, and cell division. In the first part of this review, we present the best characterized of these biochemical pathways; in the second part, we attempt to integrate these molecular details into a biological context.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 529-550 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The conserved protein-conducting channel, referred to as the Sec61 channel in eukaryotes or the SecY channel in eubacteria and archaea, translocates proteins across cellular membranes and integrates proteins containing hydrophobic transmembrane segments into lipid bilayers. Structural studies illustrate how the protein-conducting channel accomplishes these tasks. Three different mechanisms, each requiring a different set of channel binding partners, are employed to move polypeptide substrates: The ribosome feeds the polypeptide chain directly into the channel, a ratcheting mechanism is used by the eukaryotic endoplasmic reticulum chaperone BiP, and a pushing mechanism is utilized by the bacterial ATPase SecA. We review these translocation mechanisms, relating biochemical and genetic observations to the structures of the protein-conducting channel and its binding partners.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 35-56 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Apoptosis plays a central role in the development and homeostasis of metazoans. Research in the past two decades has led to the identification of hundreds of genes that govern the initiation, execution, and regulation of apoptosis. An earlier focus on the genetic and cell biological characterization has now been complemented by systematic biochemical and structural investigation, giving rise to an unprecedented level of clarity in many aspects of apoptosis. In this review, we focus on the molecular mechanisms of apoptosis by synthesizing available biochemical and structural information. We discuss the mechanisms of ligand binding to death receptors, actions of the Bcl-2 family of proteins, and caspase activation, inhibition, and removal of inhibition. Although an emphasis is given to the mammalian pathways, a comparative analysis is applied to related mechanistic information in Drosophila and Caenorhabditis elegans.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 347-380 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The nuclear envelope (NE) is a highly specialized membrane that delineates the eukaryotic cell nucleus. It is composed of the inner and outer nuclear membranes, nuclear pore complexes (NPCs) and, in metazoa, the lamina. The NE not only regulates the trafficking of macromolecules between nucleoplasm and cytosol but also provides anchoring sites for chromatin and the cytoskeleton. Through these interactions, the NE helps position the nucleus within the cell and chromosomes within the nucleus, thereby regulating the expression of certain genes. The NE is not static, rather it is continuously remodeled during cell division. The most dramatic example of NE reorganization occurs during mitosis in metazoa when the NE undergoes a complete cycle of disassembly and reformation. Despite the importance of the NE for eukaryotic cell life, relatively little is known about its biogenesis or many of its functions. We thus are far from understanding the molecular etiology of a diverse group of NE-associated diseases.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 605-631 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Adult tissue-specific stem cells have the capacity to self-renew and generate functional differentiated cells that replenish lost cells throughout an organism's lifetime. Studies on stem cells from diverse systems have shown that stem cell function is controlled by extracellular cues from the niche and by intrinsic genetic programs within the stem cell. Here, we review the remarkable progress recently made in research regarding the stem cell niche. We compare the differences and commonalities of different stem cell niches in Drosophila ovary/testis and Caenorhabditis elegans distal tip, as well as in mammalian bone marrow, skin/hair follicle, intestine, brain, and testis. On the basis of this comparison, we summarize the common features, structure, and functions of the stem cell niche and highlight important niche signals that are conserved from Drosophila to mammals. We hope this comparative summary defines the basic elements of the stem cell niche, providing guiding principles for identification of the niche in other systems and pointing to areas for future studies.
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  • 91
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 659-693 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The TGF-?‚ family comprises many structurally related differentiation factors that act through a heteromeric receptor complex at the cell surface and an intracellular signal transducing Smad complex. The receptor complex consists of two type II and two type I transmembrane serine/threonine kinases. Upon phosphorylation by the receptors, Smad complexes translocate into the nucleus, where they cooperate with sequence-specific transcription factors to regulate gene expression. The vertebrate genome encodes many ligands, fewer type II and type I receptors, and only a few Smads. In contrast to the perceived simplicity of the signal transduction mechanism with few Smads, the cellular responses to TGF-?‚ ligands are complex and context dependent. This raises the question of how the specificity of the ligand-induced signaling is achieved. We review the molecular basis for the specificity and versatility of signaling by the many ligands through this conceptually simple signal transduction mechanism.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 81-103 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Sphingolipids and glycosphingolipids are membrane components of eukaryotic cell surfaces. Their constitutive degradation takes place on the surface of intra-endosomal and intra-lysosomal membrane structures. During endocytosis, these intra-lysosomal membranes are formed and prepared for digestion by a lipid-sorting process during which their cholesterol content decreases and the concentration of the negatively charged bis(monoacylglycero)phosphate (BMP)Đ??erroneously also called lysobisphosphatidic acid (LBPA)Đ??increases. Glycosphingolipid degradation requires the presence of water-soluble acid exohydrolases, sphingolipid activator proteins, and anionic phospholipids like BMP. The lysosomal degradation of sphingolipids with short hydrophilic head groups requires the presence of sphingolipid activator proteins (SAPs). These are the saposins (Saps) and the GM2 activator protein. Sphingolipid activator proteins are membrane-perturbing and lipid-binding proteins with different specificities for the bound lipid and the activated enzyme-catalyzed reaction. Their inherited deficiency leads to sphingolipid- and membrane-storage diseases. Sphingolipid activator proteins not only facilitate glycolipid digestion but also act as glycolipid transfer proteins facilitating the association of lipid antigens with immunoreceptors of the CD1 family.
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    Annual Review of Cell and Developmental Biology 21 (2005), S. 297-318 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: RNA silencing refers to a broad range of phenomena sharing the common feature that large, double-stranded RNAs or stem-loop precursors are processed to ca. 21Đ??26 nucleotide small RNAs, which then guide the cleavage of cognate RNAs, block productive translation of these RNAs, or induce methylation of specific target DNAs. Although the core mechanisms are evolutionarily conserved, epigenetic maintenance of silencing by amplification of small RNAs and the elaboration of mobile, RNA-based silencing signals occur predominantly in plants. Plant RNA silencing systems are organized into a network with shared components and overlapping functions. MicroRNAs, and probably trans-acting small RNAs, help regulate development at the posttranscriptional level. Small interfering RNAs associated with transgene- and virus-induced silencing function primarily in defending against foreign nucleic acids. Another system, which is concerned with RNA-directed methylation of DNA repeats, seems to have roles in epigenetic silencing of certain transposable elements and genes under their control.
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    Annual Review of Ecology, Evolution, and Systematics 36 (2005), S. 169-189 
    ISSN: 1543-592X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Plant secondary metabolites (PSMs) significantly impact the nutritional ecology of terrestrial vertebrate herbivores. Herbivores have a wide range of mechanisms (herbivore offenses) to mitigate the negative effects of PSMs. We discuss several behavioral and physiological offenses used by terrestrial vertebrates. Several newly recognized herbivore offenses such as regulated absorption and regulation of toxin intake are presented. We give a detailed description of the biotransformation system with respect to PSMs. We also summarize recent findings of plantĐ??animal interactions for lizards, birds, and mammals. Finally, we discuss some new tools that can be applied to long-standing questions of plantĐ??vertebrate interactions.
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    Annual Review of Genetics 39 (2005), S. 121-152 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Until around 1990, most multigene families were thought to be subject to concerted evolution, in which all member genes of a family evolve as a unit in concert. However, phylogenetic analysis of MHC and other immune system genes showed a quite different evolutionary pattern, and a new model called birth-and-death evolution was proposed. In this model, new genes are created by gene duplication and some duplicate genes stay in the genome for a long time, whereas others are inactivated or deleted from the genome. Later investigations have shown that most non-rRNA genes including highly conserved histone or ubiquitin genes are subject to this type of evolution. However, the controversy over the two models is still continuing because the distinction between the two models becomes difficult when sequence differences are small. Unlike concerted evolution, the model of birth-and-death evolution can give some insights into the origins of new genetic systems or new phenotypic characters.
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    Annual Review of Genetics 39 (2005), S. 615-651 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: In many multicellular organisms, males have one X chromosome and females have two. Dosage compensation refers to a regulatory mechanism that insures the equalization of X-linked gene products in males and females. The mechanism has been studied at the molecular level in model organisms belonging to three distantly related taxa; in these organisms, equalization is achieved by shutting down one of the two X chromosomes in the somatic cells of females, by decreasing the level of transcription of the two doses of X-linked genes in females relative to males, or by increasing the level of transcription of the single dose of X-linked genes in males. The study of dosage compensation in these different forms has revealed the existence of an amazing number of interacting chromatin remodeling mechanisms that affect the function of entire chromosomes.
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    Annual Review of Genetics 39 (2005), S. 293-307 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Although the sex of most animals is determined by genetic information, sex-determining genes had been identified only in mammals, several flies, and the worm Caenorhabditis elegans until the recent discovery of DMY (DM-domain gene on the Y chromosome) in the sex-determining region on the Y chromosome of the teleost fish medaka, Oryzias latipes. Functional and expression analyses of DMY have shown it to be the master gene for male sex determination in the medaka. The only sex-determining genes found so far in vertebrates are Sry and DMY. Therefore, the medaka is expected to become a good experimental animal for investigating the precise mechanisms involved in primary sex determination in nonmammalian vertebrates. This article reviews the origin of DMY and the sexual development of gonads in the medaka. The putative functions of DMY are also discussed.
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    Annual Review of Genetics 39 (2005), S. 241-262 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The human and mouse genome sequences bring closer the goal of understanding how characteristics of adult mammalian physiology and pathology are encoded by DNA. Here we review the challenge of understanding how genes specify mammalian traits, with particular focus on the cells and behavior of the immune system. Summarized is the emerging experience, advantages, and limitations of using ethylnitrosourea (ENU) to modify the mouse genome and select informative variants by phenotypic screens, yielding two main conclusions. First, ENU-induced variation provides an eminently feasible route to understanding how the genome encodes important mammalian processes without any prior assumptions about genes, their chromosomal locations, or expression patterns. Second, ENU alleles match those arising by natural variation. By changing individual protein domains or splice products, these alleles reveal separate gene functions specified through protein combinations.
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    Annual Review of Entomology 1 (1956), S. 1-16 
    ISSN: 0066-4170
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    Topics: Biology
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    Annual Review of Entomology 3 (1958), S. 449-468 
    ISSN: 0066-4170
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    Topics: Biology
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