ALBERT

Notes: The objective of this review is to critically assess the different approaches developed in recent years to understand the dynamics of open flows such as mixing layers, jets, wakes, separation bubbles, boundary layers, and so on. These complex flows develop in extended domains in which fluid particles are continuously advected downstream. They behave either as noise amplifiers or as oscillators, both of which exhibit strong nonlinearities ( Huerre & Monkewitz 1990 ). The local approach is inherently weakly nonparallel and it assumes that the basic flow varies on a long length scale compared to the wavelength of the instability waves. The dynamics of the flow is then considered as a superposition of linear or nonlinear instability waves that, at leading order, behave at each streamwise station as if the flow were homogeneous in the streamwise direction. In the fully global context, the basic flow and the instabilities do not have to be characterized by widely separated length scales, and the dynamics is then viewed as the result of the interactions between Global modes living in the entire physical domain with the streamwise direction as an eigendirection. This second approach is more and more resorted to as a result of increased computational capability. The earlier review of Huerre & Monkewitz (1990) emphasized how local linear theory can account for the noise amplifier behavior as well as for the onset of a Global mode. The present survey first adopts the opposite point of view by demonstrating how fully global theory accounts for the noise amplifier behavior of open flows. From such a perspective, there is strong emphasis on the very peculiar nonorthogonality of linear Global modes, which in turn allows a novel interpretation of recent numerical simulations and experimental observations. The nonorthogonality of linear Global modes also imposes severe constraints on the extension of linear global theory to the fully nonlinear re??gime. When the flow is weakly nonparallel, this limitation is so severe that the linear Global mode theory is of little help. It is then much more appropriate to develop a fully nonlinear formulation involving the presence of a front separating the base state region from the bifurcated state region.

Notes: We review the fluid mechanics and rheology of dense suspensions, emphasizing investigations of microstructure and total stress. "Dense" or "highly concentrated" suspensions are those in which the average particle separation distance is less than the particle radius. For these suspensions, multiple-body interactions as well as two-body lubrication play a significant role and the rheology is non-Newtonian. We include investigations of multimodal suspensions, but not those of suspensions with dominant nonhydrodynamic interactions. We consider results from both physical experiments and computer simulations and explore scaling theories and the development of constitutive equations.

Notes: George Gabriel Stokes died just over 100 years ago, and it has been more than 150 years since he published his great 1847 paper on water waves. The work of Stokes' precursors, which informed his early publications of 1842Đ??50, is described in the previous volume of the Annual Review of Fluid Mechanics ( Craik 2004 ). Here I examine Stokes' papers and letters concerning water waves.

Notes: Chaotic advection and, more generally, ideas from dynamical systems, have been fruitfully applied to a diverse, and varied, collection of mixing and transport problems arising in engineering applications over the past 20 years. Indeed, the "dynamical systems approach" was developed, and tested, to the point where it can now be considered a standard tool for understanding mixing and transport issues in many disciplines. This success for engineering-type flows motivated an effort to apply this approach to transport and mixing problems in geophysical flows. However, there are fundamental difficulties arising in this endeavor that must be properly understood and overcome. Central to this approach is that the starting point for analysis is a velocity field (i.e., the "dynamical system"). In many engineering applications this can be obtained sufficiently accurately, either analytically or computationally, so that it describes particle trajectories for the actual flow. However, in geophysical flows (and we concentrate here almost exclusively on oceanographic flows), the wide range of dynamically significant time and length scales makes the justification of any velocity field, in the sense of reproducing particle trajectories for the actual flow, a much more difficult matter. Nevertheless, the case for this approach is compelling due to the advances in observational capabilities in oceanography (e.g., drifter deployments, remote sensing capabilities, satellite imagery, etc.), which reveal space-time structures that are highly suggestive of the structures one visualizes in the global, geometrical study of dynamical systems theory. This has been pursued in recent years through a combination of laboratory studies, kinematic models, and dynamically consistent models that have all been compared with observational data. During the course of these studies it has become apparent that a new type of dynamical system is necessary to consider in these studies (i.e., a finite time, aperiodically time-dependent velocity field defined as a data set), which requires the development of new analytical and computational tools, as well as the necessity to discard some of the standard ideas and results from dynamical systems theory. In this article we review a number of the key developments to date in this young, but rapidly developing, area at the interface between geophysical fluid dynamics and applied and computational mathematics. We also describe the wealth of new directions for research that this approach unlocks.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Notes: Efficiently and accurately solving the equations governing fluid flow in oil reservoirs is very challenging because of the complex geological environment and the intricate properties of crude oil and gas at high pressure. We present these challenges and review successful and promising solution approaches. We discuss in detail the modeling of fluid flow in reservoirs with strongly varying rock properties. This requires subgrid-scale models that accurately represent the flow physics due to fine-scale fluctuations. A second focus is on the complex multiphase, multicomponent systems that describe miscible gas injection processes for enhanced oil recovery and CO2 sequestration.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Notes: It has recently become possible to measure the anisotropic distribution of interfaces in polycrystals and composites. Because classical theories for grain growth and coarsening assume isotropic interface properties, they are incapable of explaining how these distributions arise. The purpose of this paper is to review the results of recent experiments, simulations, and theories that document the effects of anisotropy on the capillarity-driven evolution of granular systems. The results suggest that meaningful predictions of evolving microstructural characteristics can be made using models that incorporate the anisotropy of the interfacial energy and mobility.

Notes: This review is an introduction to the problem of determining the nature of the diffraction spectra of ordered solids. After explicit computation examples of Bragg diffraction spectra of quasicrystals (bulk, surface) in kinematical and dynamical (high-resolution electron microscopy) situations, we show on simple toy models that long-range order does not necessarily lead to Bragg peaks which, in turn, are not necessarily the signature of the unique long-range periodic order.

Notes: Recent research trends of the preparation and characterization of highly efficient titanium oxideĐ??based photocatalysts are reviewed on the basis of studies done in our laboratory. Special attention is focused on the preparation and characterization of active sites of highly dispersed titanium oxide species within mesoporous matrices and on titanium oxideĐ??based binary catalysts such as Ti/Si and Ti/B oxides and unique visible light-responsive second-generation TiO2 photocatalysts prepared by an advanced metal-ion-implantation and RF magnetron sputtering deposition method. Highly dispersed titanium oxide species within mesoporous frameworks and titanium oxideĐ??based binary catalysts exhibit high and unique photocatalytic activities for various reactions, such as the direct decomposition of NOx. These species also have photo-induced superhydrophiric properties. It is of significance that visible light-responsive TiO2 photocatalysts can be applied to the decomposition of NOx in air and the degradation of pollutants in water, as well as to the splitting of water under UV and visible light irradiation.

Notes: Heterogeneous asymmetric catalysis remains a topic of intense research interest because control of enantioselectivity represents one of the major synthetic challenges today. Successful strategies to achieve high enantioselection have been developed using three key approaches: (a) adsorption of chiral modifiers onto an active metal surface, which is found to be particularly effective for enantioselective hydrogenation; (b) covalent tethering of homogeneous catalysts; and (c) electrostatic interaction between a negatively charged framework and a cation. Other approaches have been advocated, e.g., encapsulation, but in general these lead to lower enantioselectivity for these heterogeneous asymmetric systems when compared with the equivalent homogeneous catalyst. This review covers the strategies for achieving high enantioselection as well as recent interesting features concerning confinement effects, the inversion of enantioselectivity, and specific cases in which enantioselection increases with conversion, all being factors that can guide researchers to identifying improved systems.

Notes: The review highlights the state-of-the-art research regarding the application of modern in situ spectroscopic, microscopic, and electrochemical techniques to improve the understanding of the interaction of organic molecules with metal surfaces. We also consider the chemical and electrochemical processes that lead to a de-adhesion of polymers from metal surfaces. Spectroscopic techniques such as surface-enhanced infrared or Raman spectroscopy provide molecular understanding of organic molecules and water at buried metal surfaces. This information is complementary to adhesion studies by means of atomic force microscopy and de-adhesion studies of polymer layers from metals by means of a scanning Kelvin probe. Adhesion and de-adhesion mechanisms are discussed, especially those involving humid and corrosive environments, which are the predominant and most important for metal/polymer composites in engineering applications.

Notes: Chemical analysis at high spatial resolution is the domain of analytical transmission electron microscopy. Owing to rapid instrumental developments during the past decade, electron energy-loss spectroscopy offers now a spatial resolution close to 0.1 nm and an energy resolution close to 0.1 eV. This development has been accompanied by the introduction of numerous new techniques and methods for data acquisition and analysis, which are outlined in the present article. Recent results for a wide range of material systems are addressed. These comprise first-principles calculations, which have contributed to enormous progress in the calculation of near-edge fine structures, and fingerprinting methods, which are still important for the interpretation of experimental data.

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.

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.

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.

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.

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.

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.

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.

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.

Notes: Early work and recent advances in feedback control of combustion oscillations are described. The physics of combustion oscillations, most commonly caused by a coupling between acoustic waves and unsteady heat release, are discussed, and the concept of using feedback control to interrupt these interactions is introduced. Factors affecting practical implementation of feedback control, including sensors, actuators, and controller design are described, and the historical development of control strategy for combustion oscillations is reviewed. Finally, demonstrations of feedback control on full-scale combustion systems are described, and it is concluded that there is potential to apply more systematic controller designs at full scale.

Notes: Flow simulations are one of the archetypal multiscale problems. Simulations of turbulent and unsteady separated flows have to resolve a multitude of interacting scales, whereas molecular phenomena determine the structure of shocks and the validity of the no-slip boundary condition. Particle simulations of continuum and molecular phenomena can be formulated by following the motion of interacting particles that carry the physical properties of the flow. In this article we review Lagrangian, multiresolution, particle methods such as vortex methods and smooth particle hydrodynamics for the simulation of continuous flows and molecular dynamics for the simulation of flows at the atomistic scale. We review hybrid molecular-continuum simulations with an emphasis on the computational aspects of the problem. We identify the common computational characteristics of particle methods and discuss their properties that enable the formulation of a systematic framework for multiscale flow simulations.

Notes: Gravity-driven bubbly flows are a specific class of flows, where all action is provided by gravity. An industrial example is formed by the so-called bubble column: a vertical cylinder filled with liquid through which bubbles flow that are introduced at the bottom of the cylinder. On the bubble scale, gravity gives rise to buoyancy of individual bubbles. On larger scales, gravity acts on nonuniformities in the spatial bubble distribution present in the bubbly mixture. The gravity-induced flow and flow structures can increase the inhomogeneity of the bubble distribution, leading to a turbulent flow. In this flow, specific scales are identified: a large-scale circulation with the liquid flowing upward in the center of the column and downward close to the wall. On the intermediate scale there are vortical structures; eddies of liquid, with a size on the order of the diameter of the column, that stir the liquid and radially transport the bubbles. On the small scale there is the local stirring of the bubbles. We describe the ideas developed over time and identify some open questions. We discuss the experimental findings on the turbulence generated, the stability of the flow, axial dispersion, and the similarities between bubble columns and air lifts. Especially for higher gas fractions, many questions still lack accurate answers. The lateral lift force in bubble swarms and the structure of the turbulence in the bubbly mixture are important examples of inadequately understood physical phenomena, providing many challenges for fundamental and applied research on bubbly flows.

Notes: Development and optimization of multifunctional devices for fluidic manipulation of films, drops, and bubbles require detailed understanding of interfacial phenomena and microhydrodynamic flows. Systems are distinguished by a large surface to volume ratio and flow at small Reynolds, capillary, and Bond numbers are strongly influenced by boundary effects and therefore amenable to control by a variety of surface treatments and surface forces. We review the principles underlying common techniques for actuation of droplets and films on homogeneous, chemically patterned, and topologically textured surfaces by modulation of normal or shear stresses.

Notes: "What force does an insect wing generate?" Finding answers to this enduring question is an essential step toward our understanding of interactions of moving objects with fluids that enable most living species such as insects, birds, and fish to travel efficiently and us to follow similar suit with sails, oars, and airfoils. We give a brief history of research in insect flight and discuss recent findings in unsteady aerodynamics of flapping flight at intermediate range Reynolds numbers ( 10Đ??104 ). In particular, we examine the unsteady mechanisms in uniform and accelerated motions, forward and hovering flight, as well as passive flight of free-falling objects. The results obtained by "taking the insects apart" helped us to resolve previous puzzles about the force estimates in hovering insects, to ellucidate basic mechanisms essential to flapping flight, and to gain insights about the efficieny of flight.

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.

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.

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.

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.

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.

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.