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  • Articles  (9,325)
  • Springer Nature  (8,188)
  • Annual Reviews
  • 2000-2004  (9,325)
  • 2000  (9,325)
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  • Articles  (9,325)
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  • 2000-2004  (9,325)
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  • 1
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 27-47 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Owing to the rapid development of in vivo applications for non-viral gene delivery vectors, it is necessary to have a better understanding of how the structure-activity relationships of these lipid-DNA complexes are affected by their environment. Indeed, research in gene therapy first focused on in vitro cell culture studies to determine the mechanisms involved in the delivery of DNA into the cell. New biophysical techniques such as electron microscopy and X-ray diffraction have been developed to discern the structure of the lipid-DNA complex. However, further studies have revealed discrepancies between optimal lipid-DNA formulations for in vitro transfection and for in vivo administration of these vectors. Furthermore, some immune stimulatory effects have been associated with in vivo lipid-DNA administration. This review summarizes the current state of knowledge on in vitro and in vivo lipid-DNA complex transfections. New prospects of vectors for in vivo gene transfer are also discussed.
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  • 2
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 81-103 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Hundreds of acetyltransferases exist. All use a common acetyl donor-acetyl coenzyme A-and each exhibits remarkable specificity for acetyl acceptors, which include small molecules and proteins. Analysis of the primary sequences of these enzymes indicates that they can be sorted into several superfamilies. This review covers the three-dimensional structures of members of one of these superfamilies, now referred to in the literature as the GCN5-related N-acetyltransferases (GNAT), reflecting the importance of one functional category, the histone acetyltransferases. Despite the diversity of substrate specificities, members of the GNAT superfamily demonstrate remarkable similarity in protein topology and mode of acetyl coenzyme A binding, likely reflecting a conserved catalytic mechanism.
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  • 3
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 49-79 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Protein kinase C homology-1 and -2, FYVE, and pleckstrin homology domains are ubiquitous in eukaryotic signal transduction and membrane-trafficking proteins. These domains regulate subcellular localization and protein function by binding to lipid ligands embedded in cell membranes. Structural and biochemical analysis of these domains has shown that their molecular mechanisms of membrane binding depend on a combination of specific and nonspecific interactions with membrane lipids. In vivo studies of green fluorescent protein fusions have highlighted the key roles of these domains in regulating protein localization to plasma and internal membranes in cells.
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  • 4
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 1-26 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Although the force fields and interaction energies that control protein behavior can be inferred indirectly from equilibrium and kinetic measurements, recent developments have made it possible to quantify directly (a) the ranges, magnitudes, and time dependence of the interaction energies and forces between biological materials; (b) the mechanical properties of isolated proteins; and (c) the strength of single receptor-ligand bonds. This review describes recent results obtained by using the atomic force microscope, optical tweezers, the surface force apparatus, and micropipette aspiration to quantify short-range protein-ligand interactions and the long-range, nonspecific forces that together control protein behavior. The examples presented illustrate the power of force measurements to quantify directly the force fields and energies that control protein behavior.
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  • 5
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 183-212 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Cys2His2 zinc fingers are one of the most common DNA-binding motifs found in eukaryotic transcription factors. These proteins typically contain several fingers that make tandem contacts along the DNA. Each finger has a conserved betabetaalpha structure, and amino acids on the surface of the alpha-helix contact bases in the major groove. This simple, modular structure of zinc finger proteins, and the wide variety of DNA sequences they can recognize, make them an attractive framework for attempts to design novel DNA-binding proteins. Several studies have selected fingers with new specificities, and there clearly are recurring patterns in the observed side chain-base interactions. However, the structural details of recognition are intricate enough that there are no general rules (a "recognition code") that would allow the design of an optimal protein for any desired target site. Construction of multifinger proteins is also complicated by interactions between neighboring fingers and the effect of the intervening linker. This review analyzes DNA recognition by Cys2His2 zinc fingers and summarizes progress in generating proteins with novel specificities from fingers selected by phage display.
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  • 6
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 327-359 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract This review describes how kinetic experiments using techniques with dramatically improved time resolution have contributed to understanding mechanisms in protein folding. Optical triggering with nanosecond laser pulses has made it possible to study the fastest-folding proteins as well as fundamental processes in folding for the first time. These include formation of alpha-helices, beta-sheets, and contacts between residues distant in sequence, as well as overall collapse of the polypeptide chain. Improvements in the time resolution of mixing experiments and the use of dynamic nuclear magnetic resonance methods have also allowed kinetic studies of proteins that fold too fast (〉 103 s-1) to be observed by conventional methods. Simple statistical mechanical models have been extremely useful in interpreting the experimental results. One of the surprises is that models originally developed for explaining the fast kinetics of secondary structure formation in isolated peptides are also successful in calculating folding rates of single domain proteins from their native three-dimensional structure.
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  • 7
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 411-438 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract ClC-type chloride channels are ubiquitous throughout the biological world. Expressed in nearly every cell type, these proteins have a host of biological functions. With nine distinct homologues known in eukaryotes, the ClCs represent the only molecularly defined family of chloride channels. ClC channels exhibit features of molecular architecture and gating mechanisms unprecedented in other types of ion channels. They form two-pore homodimers, and their voltage-dependence arises not from charged residues in the protein, but rather via coupling of gating to the movement of chloride ions within the pore. Because the functional characteristics of only a few ClC channels have been studied in detail, we are still learning which properties are general to the whole family. New approaches, including structural analyses, will be crucial to an understanding of ClC architecture and function.
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  • 8
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 439-461 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract In the past decade, a general design for sequence-specific minor groove ligands has evolved, based on the natural products distamycin and netropsin. By utilizing a basic set of design rules for connecting pyrrole, imidazole, and hydroxypyrrole modules, new ligands can be prepared to target almost any sequence of interest with both high affinity and specificity. In this review we present the design rules with a brief history of how they evolved. The structural basis for sequence-specific recognition is explained, together with developments that allow linking of recognition modules that enable targeting of long DNA sequences. Examples of the affinity and specificity that can be achieved with a number of variations on the basic design are given. Recently these molecules have been used to compete with proteins both in vitro and in vivo, and a brief description of the experimental results are given.
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  • 9
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 1-33 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract I have had a very fortunate career in astronomy, benefiting greatly from numerous accidents of fate. I grew up in Cincinnati, Ohio, served in the US Army Air Force in World War II, and had all my further education at the University of Chicago, from PhB in the College to PhD in astronomy and astrophysics. There, as a postdoc at Princeton University, and as a young faculty member at Caltech and Mount Wilson and Palomar Observatories, I had excellent teachers and mentors. I have done research primarily on gaseous nebulae and active galactic nuclei, but also made a few early contributions on stellar interiors and the heating in the outer layers of the Sun. The major part of my scientific career was at the University of Wisconsin and Lick Observatory, but I also had three productive years at the Institute for Advanced Study.
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  • 10
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 289-335 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract ROSAT observations indicate that approximately half of all nearby groups of galaxies contain spatially extended X-ray emission. The radial extent of the X-ray emission is typically 50-500 h-1100 kpc or approximately 10-50% of the virial radius of the group. Diffuse X-ray emission is generally restricted to groups that contain at least one early-type galaxy. X-ray spectroscopy suggests the emission mechanism is most likely a combination of thermal bremsstrahlung and line emission. This interpretation requires that the entire volume of groups be filled with a hot, low-density gas known as the intragroup medium. ROSAT and ASCA observations indicate that the temperature of the diffuse gas in groups ranges from approximately 0.3 keV to 2 keV. Higher temperature groups tend to follow the correlations found for rich clusters between X-ray luminosity, temperature, and velocity dispersion. However, groups with temperatures below approximately 1 keV appear to fall off the cluster LX-T relationship (and possibly the LX-sigma and sigma-T cluster relationships, although evidence for these latter departures is at the present time not very strong). Deviations from the cluster LX-T relationship are consistent with preheating of the intragroup medium by an early generation of stars and supernovae. There is now considerable evidence that most X-ray groups are real, physical systems and not chance superpositions or large-scale filaments viewed edge-on. Assuming the intragroup gas is in hydrostatic equilibrium, X-ray observations can be used to estimate the masses of individual systems. ROSAT observations indicate that the typical mass of an X-ray group is ~1013 h-1100 M out to the radius to which X-ray emission is currently detected. The observed baryonic masses of groups are a small fraction of the X-ray determined masses, which implies that groups are dominated by dark matter. On scales of the virial radius, the dominant baryonic component in groups is likely the intragroup medium.
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  • 11
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 485-519 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract The brown dwarfs occupy the gap between the least massive star and the most massive planet. They begin as dimly stellar in appearance and experience fusion (of at least deuterium) in their interiors. But they are never able to stabilize their luminosity or temperature and grow ever fainter and cooler with time. For that reason, they can be viewed as a constituent of baryonic "dark matter." Indeed, we currently have a hard time directly seeing an old brown dwarf beyond 100 pc. After 20 years of searching and false starts, the first confirmed brown dwarfs were announced in 1995. This was due to a combination of increased sensitivity, better search strategies, and new means of distinguishing substellar from stellar objects. Since then, a great deal of progress has been made on the observational front. We are now in a position to say a substantial amount about actual brown dwarfs. We have a rough idea of how many of them occur as solitary objects and how many are found in binary systems. We have obtained the first glimpse of atmospheres intermediate in temperature between stars and planets, in which dust formation is a crucial process. This has led to the proposal of the first new spectral classes in several decades and the need for new diagnostics for classification and setting the temperature scale. The first hints on the substellar mass function are in hand, although all current masses depend on models. It appears that numerically, brown dwarfs may well be almost as common as stars (though they appear not to contain a dynamically interesting amount of mass).
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  • 12
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 613-666 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract This review deals with the winds from "normal" hot stars such as O-stars, B- and A-supergiants, and Central Stars of Planetary Nebulae with O-type spectra. The advanced diagnostic methods of stellar winds, including an assessment of the accuracy of the determinations of global stellar wind parameters (terminal velocities, mass-loss rates, wind momenta, and energies), are introduced and scaling relations as a function of stellar parameters are provided. Observational results are interpreted in the framework of the stationary, one-dimensional (1-D) theory of line-driven winds. Systematic effects caused by nonhomogeneous structures, time dependence, and deviations from spherical symmetry are discussed. The review finishes with a brief description of the role of stellar winds as extragalactic distance indicators and as tracers of the chemical composition of galaxies at high redshift.
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  • 13
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    Annual Review of Fluid Mechanics 32 (2000), S. 137-164 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The active control of sound waves has become an extraordinarily large and vigorous area of academic research and technological development. In this paper we describe the physical principles underlying the control of sound and review their application in a wide range of contexts. One scenario involves the control of noise from a primary source by the introduction of secondary sources, and this technique is described for fields in ducts, in free space, in enclosures (with particular reference to aircraft cabins), and for turbomachinery. A second scenario involves the use of the active control of sound to eliminate large-scale oscillations in more complicated flows, in which part of an unstable feedback cycle is mediated via acoustic waves. Successful applications of this idea include the control of combustion instabilities and compressor surge.
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  • 14
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    Annual Review of Fluid Mechanics 32 (2000), S. 165-202 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract This article reviews some aspects of the roles that laboratory experiments have played in the study of orographic effects in the Earth's atmosphere and oceans. The review focuses on, but is not restricted to, physical systems for which the effects of both background stratification and rotation are important. In the past, such laboratory studies have been largely decoupled from attempts to make quantitative comparisons with the results of numerical-model studies or observations from field programs. Rather, they have been used mostly in the important task of better understanding the physics of rotating and stratified flows. Furthermore, most laboratory experiments concerned with the effects of orography on either homogeneous or stratified rotating fluids have considered laminar flows, whereas their counterpart flows in the atmosphere and ocean are turbulent. We argue that laboratory investigations are likely to be more useful in addressing critical environmental problems if the studies are more closely allied with numerical-modeling efforts. The latter, in turn, should be tied to field projects, with the overall objective of improving our ability to predict the behavior of natural systems. In this same spirit, we conclude that far more attention should be given to the laboratory simulation of the turbulent characteristics of natural flows. The availability of rapidly developing technology to acquire and analyze laboratory data provides the capability necessary to support the increasingly important roles that laboratory experiments can play in understanding and predicting the behavior of our natural environment.
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  • 15
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    Annual Review of Fluid Mechanics 32 (2000), S. 241-274 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract We concentrate on the rich effects that surface tension has on free and forced surface waves for linear, nonlinear, and especially strongly nonlinear waves close to or at breaking or their limiting form. These effects are discussed in the context of standing gravity and gravity-capillary waves, Faraday waves, and parasitic capillary waves. Focus is primarily on post-1989 research. Regarding standing waves, new waveforms and the large effect that small capillarity can have are considered. Faraday waves are discussed principally with regard to viscous effects, hysteresis, and limit cycles; nonlinear waveforms of low mode numbers; contact-line effects and surfactants; breaking and subharmonics; and drop ejection. Pattern formation and chaotic and nonlinear dynamics of Faraday waves are mentioned only briefly. Gravity and gravity-capillary wave generation of parasitic capillaries and dissipation are considered at length. We conclude with our view on the direction of future research in these areas.
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    Annual Review of Fluid Mechanics 32 (2000), S. 203-240 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Passive scalar behavior is important in turbulent mixing, combustion, and pollution and provides impetus for the study of turbulence itself. The conceptual framework of the subject, strongly influenced by the Kolmogorov cascade phenomenology, is undergoing a drastic reinterpretation as empirical evidence shows that local isotropy, both at the inertial and dissipation scales, is violated. New results of the complex morphology of the scalar field are reviewed, and they are related to the intermittency problem. Recent work on other aspects of passive scalar behavior-its spectrum, probability density function, flux, and variance-is also addressed.
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    Annual Review of Fluid Mechanics 32 (2000), S. 573-611 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract A vapor explosion results from the rapid and intense heat transfer that may follow contact between a hot liquid and a cold, more volatile one. Because it can happen during severe-accident sequences of a nuclear power plan, that is, when a large part of the core is molten, vapor explosions have been widely studied. The different sequences of a vapor explosion are presented, including premixing, triggering, propagation, and expansion. Typical experimental results are also analyzed to understand the involved physics. Then the different physics involved in the sequences are addressed, as well as the present experimental program.
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    Annual Review of Fluid Mechanics 32 (2000), S. 779-811 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract In the framework of the classical gas dynamics, no steady flow is induced in a gas without an external force, such as gravity, by the effect of a temperature field. In a rarefied gas, on the other hand, the temperature field of a gas (often in combination with a solid boundary) plays an important role in inducing a steady flow. In the present article, we introduce various kinds of flows induced by the temperature effect and discuss their physical mechanisms. These flows vanish in the continuum limit (the limit where the mean free path of the gas molecules tends to zero), but it has been found recently that they, strangely, affect the behavior of a gas in this limit. This interesting effect, called a ghost effect, is also discussed.
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    Annual Review of Genetics 34 (2000), S. 21-59 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Plasmid-encoded partition genes determine the dynamic localization of plasmid molecules from the mid-cell position to the 1/4 and 3/4 positions. Similarly, bacterial homologs of the plasmid genes participate in controlling the bidirectional migration of the replication origin (oriC) regions during sporulation and vegetative growth in Bacillus subtilis, but not in Escherichia coli. In E. coli, but not B. subtilis, the chromosomal DNA is fully methylated by DNA adenine methyltransferase. The E. coli SeqA protein, which binds preferentially to hemimethylated nascent DNA strands, exists as discrete foci in vivo. A single SeqA focus, which is a SeqA-hemimethylated DNA cluster, splits into two foci that then abruptly migrate bidirectionally to the 1/4 and 3/4 positions during replication. Replicated oriC copies are linked to each other for a substantial period of generation time, before separating from each other and migrating in opposite directions. The MukFEB complex of E. coli and Smc of B. subtilis appear to participate in the reorganization of bacterial sister chromosomes.
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    Annual Review of Genetics 34 (2000), S. 563-591 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract In an age when the majority of monogenic human disease genes have been identified, a particular challenge for the coming generation of human geneticists will be resolving complex polygenic and multifactorial diseases. The tools of molecular and population genetic association have much potential as well as peril in uncovering small cryptic genetic effects in disease. We have used a candidate gene approach to identify eight distinct human loci with alleles that in different ways influence the outcome of exposure to HIV-1, the AIDS virus. The successes in these gene hunts have validated the approach and illustrate the strengths and limitations of association analysis in an actual case history. The integration of genetic associations, well-described clinical cohorts, extensive basic research on AIDS pathogenesis, and functional interpretation of gene connections to disease offers a formula for detecting such genes in complex human genetic phenotypes.
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    Annual Review of Genetics 34 (2000), S. 653-686 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract In 1990, David Baltimore predicted that the 1990s would be the decade of the mouse (1). This certainly proved to be true: The mouse has contributed immensely to biological research through transgenic, embryonic stem cell (ES) knockout, and classical genetic technologies. But its usefulness as a model organism is by no means over; indeed it is still rising to its peak: The mouse as a model mammalian organism still has much to offer. This article reviews use of the mouse to dissect complex genetic traits using quantitative trait analysis, with a particular emphasis on medically important diseases.
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    Annual Review of Genetics 34 (2000), S. 479-497 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Be they prokaryotic or eukaryotic, organisms are exposed to a multitude of deoxyribonucleic acid (DNA) damaging agents ranging from ultraviolet (UV) light to fungal metabolites, like Aflatoxin B1. Furthermore, DNA damaging agents, such as reactive oxygen species, can be produced by cells themselves as metabolic byproducts and intermediates. Together, these agents pose a constant threat to an organism's genome. As a result, organisms have evolved a number of vitally important mechanisms to repair DNA damage in a high fidelity manner. They have also evolved systems (cell cycle checkpoints) that delay the resumption of the cell cycle after DNA damage to allow more time for these accurate processes to occur. If a cell cannot repair DNA damage accurately, a mutagenic event may occur. Most bacteria, including Escherichia coli, have evolved a coordinated response to these challenges to the integrity of their genomes. In E. coli, this inducible system is termed the SOS response, and it controls both accurate and potentially mutagenic DNA repair functions [reviewed comprehensively in (25) and also in (78, 94)]. Recent advances have focused attention on the umuD+C+-dependent, translesion DNA synthesis (TLS) process that is responsible for SOS mutagenesis (70, 86). Here we discuss the SOS response of E. coli and concentrate in particular on the roles of the umuD+C+ gene products in promoting cell survival after DNA damage via TLS and a primitive DNA damage checkpoint.
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    Annual Review of Genetics 34 (2000), S. 457-477 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract At a small number of mammalian loci, only one of the two copies of a gene is expressed. Just which copy is expressed depends on the sex of the parent from which that copy was inherited. Such genes are said to be imprinted. The functional haploidy implied by imprinting has a number of population genetic consequences. Moreover, since diploidy is widely believed to be advantageous, the evolution of this non-Mendelian form of expression requires an explanation. Here I examine some of the theoretical and mathematical models investigating these two aspects of imprinting. For instance, the dynamics and equilibrium properties of many models of natural selection at imprinted loci are formally equivalent to models without imprinting. And different approaches to modeling the problem of the evolution of imprinting reveal the weakness of several of the apparent predictions of various verbal hypotheses about why imprinting has evolved.
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    Annual Review of Genetics 34 (2000), S. 687-745 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Obesity is a health problem of epidemic proportions in the industrialized world. The cloning and characterization of the genes for the five naturally occurring monogenic obesity syndromes in the mouse have led to major breakthroughs in understanding the physiology of energy balance and the contribution of genetics to obesity in the human population. However, the regulation of energy balance is an extremely complex process, and it is quickly becoming clear that hundreds of genes are involved. In this article, we review the naturally occurring monogenic and polygenic obese mouse strains, as well as the large number of transgenic and knockout mouse models currently available for the study of obesity and energy balance.
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  • 25
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    Annual Review of Genetics 34 (2000), S. 499-531 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract RNA editing can be broadly defined as any site-specific alteration in an RNA sequence that could have been copied from the template, excluding changes due to processes such as RNA splicing and polyadenylation. Changes in gene expression attributed to editing have been described in organisms from unicellular protozoa to man, and can affect the mRNAs, tRNAs, and rRNAs present in all cellular compartments. These sequence revisions, which include both the insertion and deletion of nucleotides, and the conversion of one base to another, involve a wide range of largely unrelated mechanisms. Recent advances in the development of in vitro editing and transgenic systems for these varied modifications have provided a better understanding of similarities and differences between the biochemical strategies, regulatory sequences, and cellular factors responsible for such RNA processing events.
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 155-181 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Electrokinetic forces are emerging as a powerful means to drive microfluidic systems with flow channel cross-sectional dimensions in the tens of micrometers and flow rates in the nanoliter per second range. These systems provide many advantages such as improved analysis speed, improved reproducibility, greatly reduced reagent consumption, and the ability to perform multiple operations in an integrated fashion. Planar microfabrication methods are used to make these analysis chips in materials such as glass or polymers. Many applications of this technology have been demonstrated, such as DNA separations, enzyme assays, immunoassays, and PCR amplification integrated with microfluidic assays. Further development of this technology is expected to yield higher levels of functionality of sample throughput on a single microfluidic analysis chip.
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 105-153 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The majority of soluble and membrane-bound proteins in modern cells are symmetrical oligomeric complexes with two or more subunits. The evolutionary selection of symmetrical oligomeric complexes is driven by functional, genetic, and physicochemical needs. Large proteins are selected for specific morphological functions, such as formation of rings, containers, and filaments, and for cooperative functions, such as allosteric regulation and multivalent binding. Large proteins are also more stable against denaturation and have a reduced surface area exposed to solvent when compared with many individual, smaller proteins. Large proteins are constructed as oligomers for reasons of error control in synthesis, coding efficiency, and regulation of assembly. Symmetrical oligomers are favored because of stability and finite control of assembly. Several functions limit symmetry, such as interaction with DNA or membranes, and directional motion. Symmetry is broken or modified in many forms: quasisymmetry, in which identical subunits adopt similar but different conformations; pleomorphism, in which identical subunits form different complexes; pseudosymmetry, in which different molecules form approximately symmetrical complexes; and symmetry mismatch, in which oligomers of different symmetries interact along their respective symmetry axes. Asymmetry is also observed at several levels. Nearly all complexes show local asymmetry at the level of side chain conformation. Several complexes have reciprocating mechanisms in which the complex is asymmetric, but, over time, all subunits cycle through the same set of conformations. Global asymmetry is only rarely observed. Evolution of oligomeric complexes may favor the formation of dimers over complexes with higher cyclic symmetry, through a mechanism of prepositioned pairs of interacting residues. However, examples have been found for all of the crystallographic point groups, demonstrating that functional need can drive the evolution of any symmetry.
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 239-263 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract A fundamental perspective can be achieved by targeting single cells for analysis with the goal of deconvoluting complex biological functions. However, single-cell studies have their own difficulties, such as minute volumes and sample amounts. Quantitative chemical analysis of single cells has emerged as a powerful new area in recent years due to several technological advancements. The development of microelectrodes has allowed the measurement of redox-active species as a function of cellular dynamics. This miniaturization trend is also evident in the separation sciences with the application of small column separations to single cells. Desorption ionization methods with mass spectrometric detection have shown single-cell capability owing to numerous technological developments. Finally, fluorescence imaging has also progressed to the point where single-cell dynamics can be probed by native fluorescence utilizing either single or multiple photon excitation. The results of these studies are reviewed with an emphasis on the quantitation of single-cell dynamics.
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 265-289 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Vancomycin is the archetype among naturally occurring compounds known as glycopeptide antibiotics. Because it is a vital therapeutic agent used worldwide for the treatment of infections with gram-positive bacteria, emerging bacterial resistance to vancomycin is a major public health threat. Recent investigations into the mechanisms of action of glycopeptide antibiotics are driven by a need to understand their detailed mechanism of action so that new agents can be developed to overcome resistance. These investigations have revealed that glycopeptide antibiotics exhibit a rich array of complex cooperative phenomena when they bind target ligands, making them valuable model systems for the study of molecular recognition.
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 291-325 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Comparative modeling predicts the three-dimensional structure of a given protein sequence (target) based primarily on its alignment to one or more proteins of known structure (templates). The prediction process consists of fold assignment, target-template alignment, model building, and model evaluation. The number of protein sequences that can be modeled and the accuracy of the predictions are increasing steadily because of the growth in the number of known protein structures and because of the improvements in the modeling software. Further advances are necessary in recognizing weak sequence-structure similarities, aligning sequences with structures, modeling of rigid body shifts, distortions, loops and side chains, as well as detecting errors in a model. Despite these problems, it is currently possible to model with useful accuracy significant parts of approximately one third of all known protein sequences. The use of individual comparative models in biology is already rewarding and increasingly widespread. A major new challenge for comparative modeling is the integration of it with the torrents of data from genome sequencing projects as well as from functional and structural genomics. In particular, there is a need to develop an automated, rapid, robust, sensitive, and accurate comparative modeling pipeline applicable to whole genomes. Such large-scale modeling is likely to encourage new kinds of applications for the many resulting models, based on their large number and completeness at the level of the family, organism, or functional network.
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 213-238 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract In order to solve the immensely difficult protein-folding problem, it will be necessary to characterize the barriers that slow folding and the intermediate structures that promote it. Although protein-folding intermediates are not accessible to the usual structural studies, hydrogen exchange (HX) methods have been able to detect and characterize intermediates in both kinetic and equilibrium modes-as transient kinetic folding intermediates on a subsecond time scale, as labile equilibrium molten globule intermediates under destabilizing conditions, and as infinitesimally populated intermediates in the high free-energy folding landscape under native conditions. Available results consistently indicate that protein-folding landscapes are dominated by a small number of discrete, metastable, native-like partially unfolded forms (PUFs). The PUFs appear to be produced, one from another, by the unfolding and refolding of the protein's intrinsically cooperative secondary structural elements, which can spontaneously create stepwise unfolding and refolding pathways. Kinetic experiments identify three kinds of barrier processes: (a) an initial intrinsic search-nucleation-collapse process that prepares the chain for intermediate formation by pinning it into a condensed coarsely native-like topology; (b) smaller search-dependent barriers that put the secondary structural units into place; and (c) optional error-dependent misfold-reorganization barriers that can cause slow folding, intermediate accumulation, and folding heterogeneity. These conclusions provide a coherent explanation for the grossly disparate folding behavior of different globular proteins in terms of distinct folding pathways.
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 463-495 
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Photosystem II uses visible light to drive the oxidation of water, resulting in bioactivated electrons and protons, with the production of molecular oxygen as a byproduct. This water-splitting reaction is carried out by a manganese cluster/tyrosine radical ensemble, the oxygen-evolving complex. Although conventional continuous-wave, perpendicular-polarization electron paramagnetic resonance (EPR) spectroscopy has significantly advanced our knowledge of the structure and function of the oxygen-evolving complex, significant additional information can be obtained with the application of additional EPR methodologies. Specifically, parallel-polarization EPR spectroscopy can be used to obtain highly resolved EPR spectra of integer spin Mn species, and pulsed EPR spectroscopy with electron spin echo-based sequences, such as electron spin echo envelope modulation and electron spin echo-electron nuclear double resonance, can be used to measure weak interactions obscured in continuous-wave spectroscopy by inhomogeneous broadening.
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 523-543 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The ability to manipulate, stretch and twist biomolecules opens the way to an understanding of their structural transitions. We review some of the recently discovered stress-induced structural transitions in DNA as well as the application of single molecule manipulation techniques to DNA unzipping and to the study of protein folding/unfolding transitions.
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 497-521 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The genomes of higher cells consist of double-helical DNA, a densely charged polyelectrolyte of immense length. The intrinsic physical properties of DNA, as well as the properties of its complexes with proteins and ions, are therefore of fundamental interest in understanding the functions of DNA as an informational macromolecule. Because individual DNA molecules often exceed 1 cm in length, it is clear that DNA bending, folding, and interaction with nuclear proteins are necessary for packaging genomes in small volumes and for integrating the nucleotide sequence information that guides genetic readout. This review first focuses on recent experiments exploring how the shape of the densely charged DNA polymer and asymmetries in its surrounding counterion distribution mutually influence one another. Attention is then turned to experiments seeking to discover the degree to which asymmetric phosphate neutralization can lead to DNA bending in protein-DNA complexes. It is argued that electrostatic effects play crucial roles in the intrinsic, sequence-dependent shape of DNA and in DNA shapes induced by protein binding.
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 361-410 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Atomic force microscopy (AFM) has been used to study protein, nucleic acid, and virus crystals in situ, in their mother liquors, as they grow. From sequential AFM images taken at brief intervals over many hours, or even days, the mechanisms and kinetics of the growth process can be defined. The appearance of both two- and three-dimensional nuclei on crystal surfaces have been visualized, defect structures of crystals were clearly evident, and defect densities of crystals were also determined. The incorporation of a wide range of impurities, ranging in size from molecules to microns or larger microcrystals, and even foreign particles were visually recorded. From these observations and measurements, a more complex understanding of the detailed character of macromolecular crystals is emerging, one that reveals levels of complexity previously unsuspected. The unique features of these crystals, apparently in AFM images, undoubtedly influence the diffraction properties of the crystals and the quality of the molecular images obtained by X-ray crystallography.
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    Annual Review of Biophysics and Biomolecular Structure 29 (2000), S. 545-576 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract We review how motile cells regulate actin filament assembly at their leading edge. Activation of cell surface receptors generates signals (including activated Rho family GTPases) that converge on integrating proteins of the WASp family (WASp, N-WASP, and Scar/WAVE). WASP family proteins stimulate Arp2/3 complex to nucleate actin filaments, which grow at a fixed 70o angle from the side of pre-existing actin filaments. These filaments push the membrane forward as they grow at their barbed ends. Arp2/3 complex is incorporated into the network, and new filaments are capped rapidly, so that activated Arp2/3 complex must be supplied continuously to keep the network growing. Hydrolysis of ATP bound to polymerized actin followed by phosphate dissociation marks older filaments for depolymerization by ADF/cofilins. Profilin catalyzes exchange of ADP for ATP, recycling actin back to a pool of unpolymerized monomers bound to profilin and thymosin-beta4 that is poised for rapid elongation of new barbed ends.
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    Notes: Abstract Small molecules that modulate the activity of biological signaling molecules can be powerful probes of signal transduction pathways. Highly specific molecules with high affinity are difficult to identify because of the conserved nature of many protein active sites. A newly developed approach to discovery of such small molecules that relies on protein engineering and chemical synthesis has yielded powerful tools for the study of a wide variety of proteins involved in signal transduction (G-proteins, protein kinases, 7-transmembrane receptors, nuclear hormone receptors, and others). Such chemical genetic tools combine the advantages of traditional genetics and the unparalleled temporal control over protein function afforded by small molecule inhibitors/activators that act at diffusion controlled rates with targets.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 1-18 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Ethylene regulates a multitude of plant processes, ranging from seed germination to organ senescence. Of particular economic importance is the role of ethylene as an inducer of fruit ripening. Ethylene is synthesized from S-adenosyl-L-methionine via 1-aminocyclopropane-1-carboxylic acid (ACC). The enzymes catalyzing the two reactions in this pathway are ACC synthase and ACC oxidase. Environmental and endogenous signals regulate ethylene biosynthesis primarily through differential expression of ACC synthase genes. Components of the ethylene signal transduction pathway have been identified by characterization of ethylene-response mutants in Arabidopsis thaliana. One class of mutations, exemplified by etr1, led to the identification of the ethylene receptors, which turned out to be related to bacterial two-component signaling systems. Mutations that eliminate ethylene binding to the receptor yield a dominant, ethylene-insensitive phenotype. CTR1 encodes a Raf-like Ser/Thr protein kinase that acts downstream from the ethylene receptor and may be part of a MAP kinase cascade. Mutants in CTR1 exhibit a constitutive ethylene-response phenotype. Both the ethylene receptors and CTR1 are negative regulators of ethylene responses. EIN2 and EIN3 are epistatic to CTR1, and mutations in either gene lead to ethylene insensitivity. Whereas the function of EIN2 in ethylene transduction is not known, EIN3 is a putative transcription factor involved in regulating expression of ethylene-responsive genes. Biotechnological modifications of ethylene synthesis and of sensitivity to ethylene are promising methods to prevent spoilage of agricultural products such as fruits, whose ripening is induced by ethylene.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 19-49 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Chemical synaptic transmission serves as the main form of cell to cell communication in the nervous system. Neurotransmitter release occurs through the process of regulated exocytosis, in which a synaptic vesicle releases its contents in response to an increase in calcium. The use of genetic, biochemical, structural, and functional studies has led to the identification of factors important in the synaptic vesicle life cycle. Here we focus on the prominent role of SNARE (soluble NSF attachment protein receptor) proteins during membrane fusion and the regulation of SNARE function by Rab3a, nSec1, and NSF. Many of the proteins important for transmitter release have homologs involved in intracellular vesicle transport, and all forms of vesicle trafficking share common basic principles. Finally, modifications to the synaptic exocytosis pathway are very likely to underlie certain forms of synaptic plasticity and therefore contribute to learning and memory.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 113-143 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The ezrin-radixin-moesin (ERM) family of proteins have emerged as key regulatory molecules in linking F-actin to specific membrane proteins, especially in cell surface structures. Merlin, the product of the NF2 tumor suppressor gene, has sequence similarity to ERM proteins and binds to some of the same membrane proteins, but lacks a C-terminal F-actin binding site. In this review we discuss how ERM proteins and merlin are negatively regulated by an intramolecular association between their N- and C-terminal domains. Activation of at least ERM proteins can be accomplished by C-terminal phosphorylation in the presence of PIP2. We also discuss membrane proteins to which ERM and merlin bind, including those making an indirect linkage through the PDZ-containing adaptor molecules EBP50 and E3KARP. Finally, the function of these proteins in cortical structure, endocytic traffic, signal transduction, and growth control is discussed.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 145-171 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Adipogenesis, or the development of fat cells from preadipocytes, has been one of the most intensely studied models of cellular differentiation. In part this has been because of the availability of in vitro models that faithfully recapitulate most of the critical aspects of fat cell formation in vivo. More recently, studies of adipogenesis have proceeded with the hope that manipulation of this process in humans might one day lead to a reduction in the burden of obesity and diabetes. This review explores some of the highlights of a large and burgeoning literature devoted to understanding adipogenesis at the molecular level. The hormonal and transcriptional control of adipogenesis is reviewed, as well as studies on a less well known type of fat cell, the brown adipocyte. Emphasis is placed, where possible, on in vivo studies with the hope that the results discussed may one day shed light on basic questions of cellular growth and differentiation in addition to possible benefits in human health.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 173-189 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Enteropathogenic Escherichia coli (EPEC) is a gram-negative bacterial pathogen that adheres to human intestinal epithelial cells, resulting in watery, persistent diarrhea. It subverts the host cell cytoskeleton, causing a rearrangement of cytoskeletal components into a characteristic pedestal structure underneath adherent bacteria. In contrast to other intracellular pathogens that affect the actin cytoskeleton from inside the host cytoplasm, EPEC remains extracellular and transmits signals through the host cell plasma membrane via direct injection of virulence factors by a "molecular syringe," the bacterial type III secretion system. One injected factor is Tir, which functions as the plasma membrane receptor for EPEC adherence. Tir directly links extracellular EPEC through the epithelial membrane and firmly anchors it to the host cell actin cytoskeleton, thereby initiating pedestal formation. In addition to stimulating actin nucleation and polymerization in the host cell, EPEC activates several other signaling pathways that lead to tight junction disruption, inhibition of phagocytosis, altered ion secretion, and immune responses. This review summarizes recent developments in our understanding of EPEC pathogenesis and discusses similarities and differences between EPEC pedestals, focal contacts, and Listeria monocytogenes actin tails.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 191-220 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Early development of the vertebrate skeleton depends on genes that pattern the distribution and proliferation of cells from cranial neural crest, sclerotomes, and lateral plate mesoderm into mesenchymal condensations at sites of future skeletal elements. Within these condensations, cells differentiate to chondrocytes or osteoblasts and form cartilages and bones under the control of various transcription factors. In most of the skeleton, organogenesis results in cartilage models of future bones; in these models cartilage is replaced by bone by the process of endochondral ossification. Lastly, through a controlled process of bone growth and remodeling the final skeleton is shaped and molded. Significant and exciting insights into all aspects of vertebrate skeletal development have been obtained through molecular and genetic studies of animal models and humans with inherited disorders of skeletal morphogenesis, organogenesis, and growth.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 221-241 
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    Notes: Abstract Stomatal guard cells are unique as a plant cell model and, because of the depth of present knowledge on ion transport and its regulation, offer a first look at signal integration in higher plants. A large body of data indicates that Ca2+ and H+ act independently, integrating with protein kinases and phosphatases, to control the gating of the K+ and Cl- channels that mediate solute flux for stomatal movements. Oscillations in the cytosolic-free concentration of Ca2+ contribute to a signaling cassette, integrated within these events through an unusual coupling with membrane voltage for solute homeostasis. Similar cassettes are anticipated to include control pathways linked to cytosolic pH. Additional developments during the last two years point to events in membrane traffic that play equally important roles in stomatal control. Research in these areas is now adding entirely new dimensions to our understanding of guard cell signaling.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 243-271 
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    Notes: Abstract During the past decade, much progress has been made in understanding how the adult fly is built. Some old concepts such as those of compartments and selector genes have been revitalized. In addition, recent work suggests the existence of genes involved in the regionalization of the adult that do not have all the features of selector genes. Nevertheless, they generate morphological distinctions within the body plan. Here we re-examine some of the defining criteria of selector genes and suggest that these newly characterized genes fulfill many, but not all, of these criteria. Further, we propose that these genes can be classified according to the domains in which they function. Finally, we discuss experiments that address the molecular mechanisms by which selector and selector-like gene products function in the fly.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 273-300 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Cajal bodies are small nuclear organelles first described nearly 100 years ago by Ramon y Cajal in vertebrate neural tissues. They have since been found in a variety of animal and plant nuclei, suggesting that they are involved in basic cellular processes. Cajal bodies contain a marker protein of unknown function, p80-coilin, and many components involved in transcription and processing of nuclear RNAs. Among these are the three eukaryotic RNA polymerases and factors required for transcribing and processing their respective nuclear transcripts: mRNA, rRNA, and pol III transcripts. A model is discussed in which Cajal bodies are the sites for preassembly of transcriptosomes, unitary particles involved in transcription and processing of RNA. A parallel is drawn to the nucleolus and the preassembly of ribosomes, which are unitary particles involved in translation of proteins.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 301-332 
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    Notes: Abstract M cells are distinctive epithelial cells that occur only in the follicle-associated epithelia that overlie organized mucosa-associated lymphoid tissues. They are structurally and functionally specialized for transepithelial transport, delivering foreign antigens and microorganisms to organized lymphoid tissues within the mucosae of the small and large intestines, tonsils and adenoids, and airways. M cell transport is a double-edged sword: Certain pathogens exploit the features of M cells that are intended to promote uptake for the purpose of immunological sampling. Eludication of the molecular architecture of M cell apical surfaces is important for understanding the strategies that pathogens use to exploit this pathway and for utilizing M cell transport for delivery of vaccines to the mucosal immune system. This article reviews the functional and biochemical features that distinguish M cells from other intestinal cell types. In addition it synthesizes the available information on development and differentiation of organized lymphoid tissues and the specialized epithelium associated with these immune inductive sites.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 483-519 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Dynamin, a 100-kDa GTPase, is an essential component of vesicle formation in receptor-mediated endocytosis, synaptic vesicle recycling, caveolae internalization, and possibly vesicle trafficking in and out of the Golgi. In addition to the GTPase domain, dynamin also contains a pleckstrin homology domain (PH) implicated in membrane binding, a GTPase effector domain (GED) shown to be essential for self-assembly and stimulated GTPase activity, and a C-terminal proline-rich domain (PRD), which contains several SH3-binding sites. Dynamin partners bind to the PRD and may either stimulate dynamin's GTPase activity or target dynamin to the plasma membrane. Purified dynamin readily self-assembles into rings or spirals. This striking structural property supports the hypothesis that dynamin wraps around the necks of budding vesicles where it plays a key role in membrane fission. The focus of this review is on the relationship between the GTPase and self-assembly properties of dynamin and its cellular function.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 459-481 
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    Notes: Abstract Cholesterol balance is maintained by a series of regulatory pathways that control the acquisition of cholesterol from endogenous and exogenous sources and the elimination of cholesterol, facilitated by its conversion to bile acids. Over the past decade, investigators have discovered that a family of membrane-bound transcription factors, sterol regulatory element-binding proteins (SREBPs), mediate the end-product repression of key enzymes of cholesterol biosynthesis. Recently orphan members of another family of transcription factors, the nuclear hormone receptors, have been found to regulate key pathways in bile acid metabolism, thereby controlling cholesterol elimination. The study of these orphan nuclear receptors suggests their potential as targets for new drug therapies.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 521-555 
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    Notes: Abstract Voltage-gated Ca2+ channels mediate Ca2+ entry into cells in response to membrane depolarization. Electrophysiological studies reveal different Ca2+ currents designated L-, N-, P-, Q-, R-, and T-type. The high-voltage-activated Ca2+ channels that have been characterized biochemically are complexes of a pore-forming alpha1 subunit of ~190-250 kDa; a transmembrane, disulfide-linked complex of alpha2 and delta subunits; an intracellular beta subunit; and in some cases a transmembrane gamma subunit. Ten alpha1 subunits, four alpha2delta complexes, four beta subunits, and two gamma subunits are known. The Cav1 family of alpha1 subunits conduct L-type Ca2+ currents, which initiate muscle contraction, endocrine secretion, and gene transcription, and are regulated primarily by second messenger-activated protein phosphorylation pathways. The Cav2 family of alpha1 subunits conduct N-type, P/Q-type, and R-type Ca2+ currents, which initiate rapid synaptic transmission and are regulated primarily by direct interaction with G proteins and SNARE proteins and secondarily by protein phosphorylation. The Cav3 family of alpha1 subunits conduct T-type Ca2+ currents, which are activated and inactivated more rapidly and at more negative membrane potentials than other Ca2+ current types. The distinct structures and patterns of regulation of these three families of Ca2+ channels provide a flexible array of Ca2+ entry pathways in response to changes in membrane potential and a range of possibilities for regulation of Ca2+ entry by second messenger pathways and interacting proteins.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 557-589 
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    Notes: Abstract Green fluorescent protein chimerae acting as reporters for protein localization and trafficking within the secretory membrane system of living cells have been used in a wide variety of applications, including time-lapse imaging, double-labeling, energy transfer, quantitation, and photobleaching experiments. Results from this work are clarifying the steps involved in the formation, translocation, and fusion of transport intermediates; the organization and biogenesis of organelles; and the mechanisms of protein retention, sorting, and recycling in the secretory pathway. In so doing, they are broadening our thinking about the temporal and spatial relationships among secretory organelles and the membrane trafficking pathways that operate between them.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 591-626 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract SUMO (small ubiquitin-related modifier) is the best-characterized member of a growing family of ubiquitin-related proteins. It resembles ubiquitin in its structure, its ability to be ligated to other proteins, as well as in the mechanism of ligation. However, in contrast to ubiquitination-often the first step on a one-way road to protein degradation-SUMOlation does not seem to mark proteins for degradation. In fact, SUMO may even function as an antagonist of ubiquitin in the degradation of selected proteins. While most SUMO targets are still at large, available data provide compelling evidence for a role of SUMO in the regulation of protein-protein interactions and/or subcellular localization.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 627-651 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Because many viruses replicate in the nucleus of their host cells, they must have ways of transporting their genome and other components into and out of this compartment. For the incoming virus particle, nuclear entry is often one of the final steps in a complex transport and uncoating program. Typically, it involves recognition by importins (karyopherins), transport to the nucleus, and binding to nuclear pore complexes. Although all viruses take advantage of cellular signals and factors, viruses and viral capsids vary considerably in size, structure, and in how they interact with the nuclear import machinery. Influenza and adenoviruses undergo extensive disassembly prior to genome import; herpesviruses release their genome into the nucleus without immediate capsid disassembly. Polyoma viruses, parvoviruses, and lentivirus preintegration complexes are thought to enter in intact form, whereas the corresponding complexes of onco-retroviruses have to wait for mitosis because they cannot infect interphase nuclei.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 653-699 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The Myc/Max/Mad network comprises a group of transcription factors whose distinct interactions result in gene-specific transcriptional activation or repression. A great deal of research indicates that the functions of the network play roles in cell proliferation, differentiation, and death. In this review we focus on the Myc and Mad protein families and attempt to relate their biological functions to their transcriptional activities and gene targets. Both Myc and Mad, as well as the more recently described Mnt and Mga proteins, form heterodimers with Max, permitting binding to specific DNA sequences. These DNA-bound heterodimers recruit coactivator or corepressor complexes that generate alterations in chromatin structure, which in turn modulate transcription. Initial identification of target genes suggests that the network regulates genes involved in the cell cycle, growth, life span, and morphology. Because Myc and Mad proteins are expressed in response to diverse signaling pathways, the network can be viewed as a functional module which acts to convert environmental signals into specific gene-regulatory programs.
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 113-141 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract The common envelope phase of binary star evolution plays an essential role in the formation of short period systems containing a compact object. In this process, significant mass and angular momentum are lost, transforming a wide progenitor system into a close remnant binary. The pathways leading to this phase and the outcomes are described. Emphasis is placed on the conditions that are required for survival of the binary according to the results of three-dimensional hydrodynamics calculations. The evolution of high-mass systems containing neutron stars is discussed, including double neutron stars, binary pulsars, Thorne-Zytkow objects, and high- and low-mass X-ray binaries.
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 143-190 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract In this article we first review the main physical effects to be considered in the building of evolutionary models of rotating stars on the Upper Main-Sequence (MS). The internal rotation law evolves as a result of contraction and expansion, meridional circulation, diffusion processes, and mass loss. In turn, differential rotation and mixing exert a feedback on circulation and diffusion, so that a consistent treatment is necessary. We review recent results on the evolution of internal rotation and the surface rotational velocities for stars on the Upper MS, for red giants, supergiants, and W-R stars. A fast rotation enhances the mass loss by stellar winds and, conversely, high mass loss removes a lot of angular momentum. The problem of the breakup or Omega-limit is critically examined in connection with the origin of Be and LBV stars. The effects of rotation on the tracks in the HR diagram, the lifetimes, the isochrones, the blue-to-red supergiant ratios, the formation of Wolf-Rayet stars, and the chemical abundances in massive stars as well as in red giants and AGB stars are reviewed in relation to recent observations for stars in the Galaxy and Magellanic Clouds. The effects of rotation on the final stages and on the chemical yields are examined, along with the constraints placed by the periods of pulsars. On the whole, this review points out that stellar evolution is not only a function of mass M and metallicity Z, but of angular velocity Omega as well.
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 427-483 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract Our understanding of the evolution of organic molecules, and their voyage from molecular clouds to the early solar system and Earth, has changed dramatically. Incorporating recent observational results from the ground and space, as well as laboratory simulation experiments and new methods for theoretical modeling, this review recapitulates the inventory and distribution of organic molecules in different environments. The evolution, survival, transport, and transformation of organics is monitored, from molecular clouds and the diffuse interstellar medium to their incorporation into solar system material such as comets and meteorites. We constrain gas phase and grain surface formation pathways to organic molecules in dense interstellar clouds, using recent observations with the Infrared Space Observatory (ISO) and ground-based radiotelescopes. The main spectroscopic evidence for carbonaceous compounds in the diffuse interstellar medium is discussed (UV bump at 2200 A, diffuse interstellar bands, extended red emission, and infrared absorption and emission bands). We critically review the signatures and unsolved problemsrelated to the main organic components suggested to be present in the diffuse gas, such as polycyclic aromatic hydrocarbons (PAHs), fullerenes, diamonds, and carbonaceous solids. We also briefly discuss the circumstellar formation of organics around late-typestars. In the solar system, space missions to comet Halley and observations of the bright comets Hyakutake and Hale-Bopp have recently allowed a reexamination of the organic chemistry of dust and volatiles in long-period comets. We review the advances in this area and also discuss progress being made in elucidating the complex organic inventory of carbonaceous meteorites. The knowledge of organic chemistry in molecular clouds, comets, and meteorites and their common link provides constraints for the processes that lead to the origin, evolution, and distribution of life in the Galaxy.
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 761-814 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract More than a decade ago the IRAS satellite opened the realm of external galaxies for studies in the 10 to 100 mum band and discovered emission from tens of thousands of normal and active galaxies. With the 1995-1998 mission of the Infrared Space Observatory1, the next major steps in extragalactic infrared astronomy became possible: detailed imaging, spectroscopy, and spectrophotometry of many galaxies detected by IRAS, as well as deep surveys in the mid- and far-IR. The spectroscopic data reveal a wealth of detail about the nature of the energy source(s) and about the physical conditions in galaxies. ISO's surveys for the first time explore the infrared emission of distant, high-redshift galaxies. ISO's main theme in extragalactic astronomy is the role of star formation in the activity and evolution of galaxies.
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    Annual Review of Fluid Mechanics 32 (2000), S. 347-382 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The relationship between flow in the arteries, particularly the wall shear stresses, and the sites where atherosclerosis develops has motivated much of the research on arterial flow in recent decades. It is now well accepted that it is sites where shear stresses are low, or change rapidly in time or space, that are most vulnerable. These conditions are likely to prevail at places where the vessel is curved; bifurcates; has a junction, a side branch, or other sudden change in flow geometry; and when the flow is unsteady. These flows, often but not always involving flow separation or secondary motions, are also the most difficult ones in fluid mechanics to analyze or compute. In this article we review the modeling studies and experiments on steady and unsteady, two-and three-dimensional flows in arteries, and in arterial geometries most relevant in the context of atherosclerosis. These include studies of normal vessels-to identify, on the basis of the fluid mechanics, lesion foci-and stenotic vessels, to model and measure flow in vessels after the lesions have evolved into plaques sufficiently large to significantly modify the flow. We also discuss recent work that elucidates many of the pathways by which mechanical forces, primarily the wall shear stresses, are transduced to effect changes in the arterial wall at the cellular, subcellular, and genetic level.
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    Annual Review of Fluid Mechanics 32 (2000), S. 383-408 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract New developments have occurred in recent years in the field of dynamo theory. The increase in computer capacity has permitted simulations of convection-driven dynamos in rotating spherical fluid shells in parameter ranges much closer to those of the Earth's core than has been possible before. The progress in handling flows of liquid sodium in large containers, on the other hand, has opened opportunities for realizations of homogeneous dynamos in the laboratory. These developments will lead to a deeper understanding of the origin of magnetic fields in planets and in stars.
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    Annual Review of Fluid Mechanics 32 (2000), S. 519-571 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The single-point statistics of turbulence in the 'roughness sub-layer' occupied by the plant canopy and the air layer just above it differ significantly from those in the surface layer. The mean velocity profile is inflected, second moments are strongly inhomogeneous with height, skewnesses are large, and second-moment budgets are far from local equilibrium. Velocity moments scale with single length and time scales throughout the layer rather than depending on height. Large coherent structures control turbulence dynamics. Sweeps rather than ejections dominate eddy fluxes and a typical large eddy consists of a pair of counter-rotating streamwise vortices, the downdraft between the vortex pair generating the sweep. Comparison with the statistics and instability modes of the plane mixing layer shows that the latter rather than the boundary layer is the appropriate model for canopy flow and that the dominant large eddies are the result of an inviscid instability of the inflected mean velocity profile. Aerodynamic drag on the foliage is the cause both of the unstable inflected velocity profile and of a 'spectral short cut' mechanism that removes energy from large eddies and diverts it to fine scales, where it is rapidly dissipated, bypassing the inertial eddy-cascade. Total dissipation rates are very large in the canopy as a result of the fine-scale shear layers that develop around the foliage.
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    Annual Review of Fluid Mechanics 32 (2000), S. 477-518 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Lava flows are gravity currents of partially molten rock that cool as they flow, in some cases melting the surface over which they flow but in all cases gradually solidifying until they come to rest. They present a wide range of flow regimes from turbulent channel flows at moderate Reynolds numbers to extremely viscous or plastic, creeping flows, and even brittle rheology may play a role once some solid has formed. The cooling is governed by the coupling of heat transport in the flowing lava with transfer from the lava surface into the surrounding atmosphere or water or into the underlying solid, and it leads to large changes in rheology. Instabilities, mostly resulting from cooling, lead to flow branching, surface folding, rifting, and fracturing, and they contribute to the distinctive styles and surface appearances of different classes of flows. Theoretical and laboratory models have complemented field studies in developing the current understanding of lava flows, motivated by the extensive roles they play in the development of planetary crusts and ore deposits and by the immediate hazards posed to people and property. However, much remains to be learned about the mechanics governing creeping, turbulent, and transitional flows in the presence of large rheology change on cooling and particularly about the advance of flow fronts, flow instabilities, and the development of flow morphology. I introduce the dynamical problems involved in the study of lava flows and review modeling approaches.
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    Annual Review of Fluid Mechanics 32 (2000), S. 659-708 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Predicting the motion of bubbles in dispersed flows is a key problem in fluid mechanics that has a bearing on a wide range of applications from oceanography to chemical engineering. In this review we synthesize the recent progress made in describing bubble motion in inhomogeneous flow. A trident approach consisting of experimental, analytical, and numerical work has given a clearer description of the hydrodynamic forces experienced by isolated bubbles moving either in inviscid flows or in slightly viscous laminar flows. A significant part of the paper is devoted to a discussion of drag, added-mass force, and shear-induced lift experienced by spheroidal bubbles moving in inertially dominated, time-dependent, rotational, nonuniform flows. The important influence of surfactants and shape distortion on bubble motion in a quiescent liquid is highlighted. Examples of bubble motion in inhomogeneous flows combining several of the effects mentioned above are discussed.
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    Annual Review of Fluid Mechanics 32 (2000), S. 709-778 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract This review summarizes results for Rayleigh-Benard convection that have been obtained over the past decade or so. It concentrates on convection in compressed gases and gas mixtures with Prandtl numbers near one and smaller. In addition to the classical problem of a horizontal stationary fluid layer heated from below, it also briefly covers convection in such a layer with rotation about a vertical axis, with inclination, and with modulation of the vertical acceleration.
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    Annual Review of Genetics 34 (2000), S. 165-186 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Filamentous fungi grow as a multicellular, multinuclear network of filament-shaped cells called hyphae. A fungal individual can be viewed as a fluid, dynamic system that is characterized by hyphal tip growth, branching, and hyphal fusion (anastomosis). Hyphal anastomosis is especially important in such nonlinear systems for the purposes of communication and homeostasis. Filamentous fungi can also undergo hyphal fusion with different individuals to form heterokaryons. However, the viability of such heterokaryons is dependent upon genetic constitution at heterokaryon incompatibility (het) loci. If hyphal fusion occurs between strains that differ in allelic specificity at het loci, vegetative incompatibility, which is characterized by hyphal compartmentation and cell lysis, is induced. This review covers microscopic and genetic analysis of hyphal fusion and the molecular and genetic analysis of the consequence of hyphal fusion between individuals that differ in specificity at het loci in filamentous ascomycetes.
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    Annual Review of Genetics 34 (2000), S. 187-204 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Mechanisms for repetition of DNA pose both opportunities and challenges to a functional genome: opportunities for increasing gene expression by amplification of useful sequences, and challenges of controlling amplification by unwanted sequences such as transposons and viruses. Experiments in numerous organisms have suggested the likely existence of a general mechanism for recognition of repeated character in DNA. This review focuses (a) on the nature of these recognition mechanisms, and (b) on types of chromatin modification and gene silencing that are used to control repeated DNA.
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    Annual Review of Genetics 34 (2000), S. 205-232 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Courtship is a complex behavior in Drosophila that recruits a wide range of genes for its realization, including those concerning sex determination, ion channels, and circadian rhythms. Results from different experimental approaches-behavioral and genetic comparisons between species, analysis of mutants and mosaics, and identification of specific sensory stimuli-sketch the outlines of a set of pleiotropic genes acting on a distributed system in the brain to produce the species-specific sequence of responses and actions.
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    Annual Review of Genetics 34 (2000), S. 297-329 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Cytogenetic imbalance in the newborn is a frequent cause of mental retardation and birth defects. Although aneuploidy accounts for the majority of imbalance, structural aberrations contribute to a significant fraction of recognized chromosomal anomalies. This review describes the major classes of constitutional, structural cytogenetic abnormalities and recent studies that explore the molecular mechanisms that bring about their de novo occurrence. Genomic features flanking the sites of recombination may result in susceptibility to chromosomal rearrangement. One such substrate for recombination is low-copy region-specific repeats. The identification of genome architectural features conferring susceptibility to rearrangements has been accomplished using methods that enable investigation of regions of the genome that are too small to be visualized by traditional cytogenetics and too large to be resolved by conventional gel electrophoresis. These investigations resulted in the identification of previously unrecognized structural cytogenetic anomalies, which are associated with genetic syndromes and allowed for the molecular basis of some chromosomal rearrangements to be delineated.
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    Annual Review of Genetics 34 (2000), S. 331-358 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Telomeres are DNA and protein structures that form complexes protecting the ends of chromosomes. Understanding of the mechanisms maintaining telomeres and insights into their function have advanced considerably in recent years. This review summarizes the currently known components of the telomere/telomerase functional complex, and focuses on how they act in the control of processes occurring at telomeres. These include processes acting on the telomeric DNA and on telomeric proteins. Key among them are DNA replication and elongation of one telomeric DNA strand by telomerase. In some situations, homologous recombination of telomeric and subtelomeric DNA is induced. All these processes act to replenish or restore telomeres. Conversely, degradative processes that shorten telomeric DNA, and nonhomologous end-joining of telomeric DNA, can lead to loss of telomere function and genomic instability. Hence they too must normally be tightly controlled.
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    Annual Review of Genetics 34 (2000), S. 439-456 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Early genetic studies identified the Escherichia coli groES and groEL genes because mutations in them blocked the growth of bacteriophages lamba and T4. Subsequent genetic and biochemical analyses have shown that GroES and GroEL constitute a chaperonin machine, absolutely essential for E. coli growth, because it is needed for the correct folding of many of its proteins. In spite of very little sequence identity to GroES, the bacteriophage T4-encoded Gp31 protein and the bacteriophage RB49-encoded CocO protein are bona fide GroEL cochaperonins, even capable of substituting for GroES in E. coli growth. A major functional distinction is that only Gp31 and CocO can assist GroEL in the correct folding of Gp23, the major bacteriophage capsid protein. Conserved structural features between CocO and Gp31, which are absent from GroES, highlight their potential importance in specific cochaperonin function.
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    Annual Review of Genetics 34 (2000), S. 593-622 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Knowledge of both prokaryotic and eukaryotic organisms is essential to the study of molecular evolution. Their common ancestry mandates that their molecular functions share many aspects of adaptation and constraint, yet their differences in size, ploidy, and structural complexity also give rise to divergent evolutionary options. We explore the interplay of adaptation, constraint, and neutrality in their evolution by the use of genetic variants to probe molecular function in context of molecular structure, metabolic organization, and phenotype-environment interactions. Case studies ranging from bacteria to butterflies, flies, and vertebrates emphasize, among other points: a. the importance of moving from initial recording of evolutionary pattern variation to studying the processes underlying the patterns, by experiment, reconstructive inference, or both; b. the complementarity, not conflict, of finding different performance and fitness impacts of natural variants in prokaryotes or eukaryotes, depending on the nature and magnitude of the variants, their locations and roles in pathways, the nature of molecular function affected, and the resulting organismal phenotype-environment interactions leading to selection or its absence; c. the importance of adaptive functional interaction of different kinds of variants, as in gene expression variants versus variants altering polypeptide properties, or interaction of changes in enzymes' active sites with complementary changes elsewhere that adjust catalytic function in different ways, or coadaptation of different steps' properties in pathways; d. the power afforded by combining structural and functional analyses of variants with study of the variants' phenotype-environment interactions to understand how molecular changes affect (or fail to affect) adaptive mechanisms "in the wild." Comparative study of prokaryotes and eukaryotes in this multifaceted way promises to deliver both new insights into evolution and a host of new and productive questions about it.
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    Annual Review of Genetics 34 (2000), S. 61-76 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Intein is the protein equivalent of intron and has been discovered in increasing numbers of organisms and host proteins. A self-splicing intein catalyzes its own removal from the host protein through a posttranslational process of protein splicing. A mobile intein displays a site-specific endonuclease activity that confers genetic mobility to the intein through intein homing. Recent findings of intein structure and the mechanism of protein splicing illuminated how inteins work and yielded clues regarding intein's origin, spread, and evolution. Inteins can evolve into new structures and new functions, such as split inteins that do trans-splicing. The structural basis of intein function needs to be identified for a full understanding of the origin and evolution of this marvelous genetic element.
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    Annual Review of Genetics 34 (2000), S. 77-137 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract The past decade has seen an explosive increase in information about regulation of eukaryotic gene transcription, especially for protein-coding genes. The most striking advances in our knowledge of transcriptional regulation involve the chromatin template, the large complexes recruited by transcriptional activators that regulate chromatin structure and the transcription apparatus, the holoenzyme forms of RNA polymerase II involved in initiation and elongation, and the mechanisms that link mRNA processing with its synthesis. We describe here the major advances in these areas, with particular emphasis on the modular complexes associated with RNA polymerase II that are targeted by activators and other regulators of mRNA biosynthesis.
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    Annual Review of Genetics 34 (2000), S. 139-164 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract A number of techniques have been developed to assess the expression of microbial virulence genes within the host (in vivo). These studies have shown that bacteria employ a wide variety of mechanisms to coordinately regulate the expression of these genes during infection. Two tenets have emerged from these studies: bacterial adaptation responses are critical to growth within the host, and interactions between microorganisms and the microenvironments of their hosts cannot be revealed from in vitro studies alone. Results that support these tenets include (i) the prevalent class of in vivo expressed genes are involved in adaptation to environmental stresses, (ii) pathogens recovered from host tissues (versus laboratory growth) are often more resistant to host killing mechanisms, and (iii) virulence gene expression can differ in the animal compared to laboratory media. Thus, pathogenicity comprises the unique ability to adapt to the varied host milieus encountered as the infection proceeds.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 51-87 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The inner membranes of eubacteria and mitochondria, as well as the chloroplast thylakoid membrane, contain essential proteins that function in oxidative phosphorylation and electron transport processes or in photosynthesis. Because most of the organellar proteins are nuclear encoded, they are synthesized in the cytoplasm and subsequently imported into the organelle before they are inserted into the membrane. This review focuses on the pathways of protein insertion into the inner membrane of eubacteria and mitochondria and into the chloroplast thylakoid membrane. In many respects, insertion of proteins into the inner membrane of bacteria is a process similar to that used by proteins of the thylakoid membrane. In both of these systems a signal recognition particle (SRP) and a SecYE-translocase are involved, as in translocation into the endoplasmic reticulum. The pathway of proteins into the mitochondrial membranes appears to be different in that it involves no SecYE-like components. A conservative pathway, recently identified in mitochondria, involves the Oxa1 protein for the insertion of proteins from the matrix. The presence of Oxa1 homologues in eubacteria and chloroplasts suggests that this pathway is evolutionarily conserved.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 89-111 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The microtubule cytoskeleton is a highly regulated system. At different times in the cell cycle and positions within the organism, microtubules can be very stable or highly dynamic. Stability and dynamics are regulated by interaction with a large number of proteins that themselves may change at specific points in the cell cycle. Exogenous ligands can disrupt the normal processes by either increasing or decreasing microtubule stability and inhibiting their dynamic behavior. The recent determination of the structure of tubulin, the main component of microtubules, makes it possible now to begin to understand the details of these interactions. We review here the structure of the tubulin dimer, with particular regard to how proteins and drugs may bind and modulate microtubule dynamics.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 333-364 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Many bisexual flowering plants possess a reproductive strategy called self-incompatibility (SI) that enables the female tissue (the pistil) to reject self but accept non-self pollen for fertilization. Three different SI mechanisms are discussed, each controlled by two separate, highly polymorphic genes at the S-locus. For the Solanaceae and Papaveraceae types, the genes controlling female function in SI, the S-RNase gene and the S-gene, respectively, have been identified. For the Brassicaceae type, the gene controlling male function, SCR/SP11, and the gene controlling female function, SRK, have been identified. The S-RNase based mechanism involves degradation of RNA of self-pollen tubes; the S-protein based mechanism involves a signal transduction cascade in pollen, including a transient rise in [Ca2+]i and subsequent protein phosphorylation/dephosphorylation; and the SRK (a receptor kinase) based mechanism involves interaction of a pollen ligand, SCR/SP11, with SRK, followed by a signal transduction cascade in the stigmatic surface cell.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 365-392 
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Retinylidene proteins, containing seven membrane-embedded alpha-helices that form an internal pocket in which the chromophore retinal is bound, are ubiquitous in photoreceptor cells in eyes throughout the animal kingdom. They are also present in a diverse range of other organisms and locations, such as archaeal prokaryotes, unicellular eukaryotic microbes, the dermal tissue of frogs, the pineal glands of lizards and birds, the hypothalamus of toads, and the human brain. Their functions include light-driven ion transport and phototaxis signaling in microorganisms, and retinal isomerization and various types of photosignal transduction in higher animals. The aims of this review are to examine this group of photoactive proteins as a whole, to summarize our current understanding of structure/function relationships in the best-studied examples, and to report recent new developments.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 393-421 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract Cell walls separate individual plant cells. To enable essential intercellular communication, plants have evolved membrane-lined channels, termed plasmodesmata, that interconnect the cytoplasm between neighboring cells. Historically, plasmodesmata were viewed as facilitating traffic of low-molecular weight growth regulators and nutrients critical to growth. Evidence for macromolecular transport via plasmodesmata was solely based on the exploitation of plasmodesmata by plant viruses during infectious spread. Now plasmodesmata are revealed to transport endogenous proteins, including transcription factors important for development. Two general types of proteins, non-targeted and plasmodesmata-targeted, traffic plasmodesmata channels. Size and subcellular location influence non-targeted protein transportability. Superimposed on cargo-specific parameters, plasmodesmata themselves fluctuate in aperture between closed, open, and dilated. Furthermore, plasmodesmata alter their transport capacity temporally during development and spatially in different regions of the plant. Plasmodesmata are exposed as major gatekeepers of signaling molecules that facilitate or regulate developmental programs, maintain physiological status, and respond to pathogens.
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    Annual Review of Cell and Developmental Biology 16 (2000), S. 423-457 
    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Abstract The closely related bacterial pathogens Neisseria gonorrhoeae (gonococci, GC) and N. meningitidis (meningococci, MC) initiate infection at human mucosal epithelia. Colonization begins at apical epithelial surfaces with a multistep adhesion cascade, followed by invasion of the host cell, intracellular persistence, transcytosis, and exit. These activities are modulated by the interaction of a panoply of virulence factors with their cognate host cell receptors, and signals are sent from pathogen to host and host to pathogen at multiple stages of the adhesion cascade. Recent advances place us on the verge of understanding the colonization process at a molecular level of detail. In this review we describe the Neisseria virulence factors in the context of epithelial cell biology, placing special emphasis on the signaling functions of type IV pili, pilus-based twitching motility, and the Opa and Opc outermembrane adhesin/invasin proteins. We also summarize what is known about bacterial intracellular trafficking and growth. With the accelerated integration of tools from cell biology, biochemistry, biophysics, and genomics, experimentation in the next few years should bring unprecedented insights into the interactions of Neisseriae with their host.
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 35-77 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract During the last decade, the understanding of fine features of the structure and evolution of stars has become possible as a result of enormous progress made in the acquisition of high-quality observational and experimental data, and of new developments and refinements in the theoretical description of stellar plasmas. The confrontation of high-quality observations with sophisticated stellar models has allowed many aspects of the theory to be validated, and several characteristics of stars relevant to Galactic evolution and cosmology to be inferred. This paper is a review of the results of recent studies undertaken in the context of the Hipparcos mission, taking benefit of the high-quality astrometric data it has provided. Successes are discussed, as well as the problems that have arisen and suggestions proposed to solve them. Future observational and theoretical developments expected and required in the field are also presented.
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 191-230 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract Because calibrated light curves of type Ia supernovae have become a major tool to determine the local expansion rate of the universe and also its geometrical structure, considerable attention has been given to models of these events over the past couple of years. There are good reasons to believe that perhaps most type Ia supernovae are the explosions of white dwarfs that have approached the Chandrasekhar mass, , and are disrupted by thermonuclear fusion of carbon and oxygen. However, the mechanism whereby such accreting carbon-oxygen white dwarfs explode continues to be uncertain. Recent progress in modeling type Ia supernovae as well as several of the still open questions are addressed in this review. Although the main emphasis is on studies of the explosion mechanism itself and on the related physical processes, including the physics of turbulent nuclear combustion in degenerate stars, we also discuss observational constraints.
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 337-377 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract Since the discovery of the first bona-fide brown dwarfs and extra-solar planets in 1995, the field of low-mass stars and substellar objects has progressed considerably, both from theoretical and observational viewpoints. Recent developments in the physics entering the modeling of these objects have led to significant improvements in the theory and to a better understanding of these objects' mechanical and thermal properties. This theory can now be confronted with observations directly in various observational diagrams (color-color, color-magnitude, mass-magnitude, mass-spectral type), a stringent and unavoidable constraint that became possible only recently with the generation of synthetic spectra. In this paper we present the current state-of-the-art general theory of low-mass stars and sub stellar objects, from one solar mass to one Jupiter mass, regarding primarily their interior structure and evolution. This review is a natural complement to the previous review by Allard et al (1997) on the atmosphere of low-mass stars and brown dwarfs. Special attention is devoted to the comparison of the theory with various available observations. The contribution of low-mass stellar and sub stellar objects to the Galactic mass budget is also analyzed.
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 379-425 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract The discovery of counterparts in X-ray and optical to radio wavelengths has revolutionized the study of gamma-ray bursts, until recently the most enigmatic of astrophysical phenomena. We now know that gamma-ray bursts are the biggest explosions in nature, caused by the ejection of ultrarelativistic matter from a powerful energy source and its subsequent collision with its environment. We have just begun to uncover a connection between supernovae and gamma-ray bursts, and are finally constraining the properties of the ultimate source of gamma-ray burst energy. We review here the observations that have led to this breakthrough in the field; we describe the basic theory of the fireball model and discuss the theoretical understanding that has been gained from interpreting the new wealth of data on gamma-ray bursts.
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    Annual Review of Fluid Mechanics 32 (2000), S. 93-136 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract This review pertains to the body of work dealing with internal recirculating flows generated by the motion of one or more of the containing walls. These flows are not only technologically important, they are of great scientific interest because they display almost all fluid mechanical phenomena in the simplest of geometrical settings. Thus corner eddies, longitudinal vortices, nonuniqueness, transition, and turbulence all occur naturally and can be studied in the same closed geometry. This facilitates the comparison of results from experiment, analysis, and computation over the whole range of Reynolds numbers. Considerable progress has been made in recent years in the understanding of three-dimensional flows and in the study of turbulence. The use of direct numerical simulation appears very promising.
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    Annual Review of Fluid Mechanics 32 (2000), S. 275-308 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract An overview of the near and far-field breakup and atomization of a liquid jet by a high speed annular gas jet is presented. The various regimes of liquid jet breakup are discussed in the parameter space of the liquid Reynolds number, the aerodynamic Weber number, and the ratio of the momentum fluxes between the gas and the liquid streams. Recent measurements of the gas-liquid interfacial instabilities are reviewed and used to analyze the underlying physical mechanisms involved in the primary breakup of the liquid jet. This process is shown to consist of the periodic stripping of liquid sheets, or ligaments, which subsequently break up into smaller lumps or drops. Models to predict the liquid shedding frequency, as well as the global parameters of the spray such as the liquid core length and spray spreading angle are discussed and compared with the experiments. The role of the secondary liquid breakup on the far-field atomization of the liquid jet is also considered, and an attempt is made to apply the classical turbulent breakup concepts to explain qualitatively the measurement of the far-field droplet size distribution and its dependence on the liquid to gas mass and momentum flux ratios. Models for the droplet breakup frequency in the far-field region of the jet, and for the daughter-size probability density function, which account for the effect of the liquid loading on the local turbulent dissipation rate in the gas, are discussed in the context of the statistical description of the spray in the far field. The striking effect of the addition of swirl in the gas stream is also examined.
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    Annual Review of Fluid Mechanics 32 (2000), S. 409-443 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Recent developments in the study of buoyancy-driven convection, magnetoconvection, and convection-driven dynamos in rapidly rotating spherical systems, with application to the fluid parts of the metallic cores of the Earth and other planets and satellites, are reviewed. While the fluid motions driven by convection generate and sustain magnetic fields by magnetohydrodynamic dynamo processes, the pattern and strength of the convective motions that control dynamo action are critically influenced by the combined and inseparable effects of rotation, magnetic fields, and spherical geometry. Emphasis is placed on the key dynamic feature of rotating spherical magnetohydrodynamics-the interaction between the Coriolis and Lorentz forces and the resulting effect on convection and magnetohydrodynamic processes. It is shown that the small value of the Ekman number, a result of rapid rotation and small viscosity in the fluid parts of planetary cores, causes severe difficulties in modeling planetary dynamos. There exist huge disparities, as a direct consequence of a small Ekman number, in the spatial, temporal, and amplitude scales of a convection-driven dynamo. The use of hyperviscosity removes these difficulties, but at the same time it alters the key dynamics in a fundamental and undesirable way. A convection-driven dynamo solution in rotating spherical systems at a sufficiently small Ekman number that is dynamically relevant to planetary fluid cores is yet to be achieved and remains a great challenge.
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    Annual Review of Genetics 34 (2000), S. 1-19 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Boveri's idea that somatic mutations are at the root of cancer found its first specific support with the investigation of leukemia and Burkitt's lymphoma, and the discovery of the mechanism of oncogene activation by balanced translocation. The study of retinoblastoma later led to the cloning of the first antioncogene, or tumor suppressor gene, and to understanding the mechanisms by which the wild-type genes lose activity. Only a small subset of cancer involves simple mechanisms. A category of hereditary disorders called the phakomatoses provide a perspective on the chain of oncogenic events in such cancers because of two-hit precursor lesions that have a low probability of malignant transformation. The common carcinomas are much more complex and are typically genetically unstable, owing either to mutational instability or chromosomal instability.
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    Annual Review of Genetics 34 (2000), S. 255-295 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Genetic and biochemical studies in yeast and animal cells have led to the identification of many components required for endocytosis. In this review, we summarize our understanding of the endocytic machinery with an emphasis on the proteins regulating the internalization step of endocytosis and endosome fusion. Even though the overall endocytic machinery appears to be conserved between yeast and animals, clear differences exist. We also discuss the roles of phosphoinositides, sterols, and sphingolipid precursors in endocytosis, because in addition to proteins, these lipids have emerged as important determinants in the spatial and most likely temporal specificity of endocytic membrane trafficking events.
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    Annual Review of Genetics 34 (2000), S. 359-399 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Mismatch repair (MMR) systems play a central role in promoting genetic stability by repairing DNA replication errors, inhibiting recombination between non-identical DNA sequences and participating in responses to DNA damage. The discovery of a link between human cancer and MMR defects has led to an explosion of research on eukaryotic MMR. The key proteins in MMR are highly conserved from bacteria to mammals, and this conservation has been critical for defining the components of eukaryotic MMR systems. In eukaryotes, there are multiple homologs of the key bacterial MutS and MutL MMR proteins, and these homologs form heterodimers that have discrete roles in MMR-related processes. This review describes the genetic and biochemical approaches used to study MMR, and summarizes the diverse roles that MMR proteins play in maintaining genetic stability.
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    Annual Review of Genetics 34 (2000), S. 401-437 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Changes in ploidy occurred early in the diversification of some animal and plant lineages and represent an ongoing phenomenon in others. While the prevalence of polyploid lineages indicates that this phenomenon is a common and successful evolutionary transition, whether polyploidization itself has a significant effect on patterns and rates of diversification remains an open question. Here we review evidence for the creative role of polyploidy in evolution. We present new estimates for the incidence of polyploidy in ferns and flowering plants based on a simple model describing transitions between odd and even base chromosome numbers. These new estimates indicate that ploidy changes may represent from 2 to 4% of speciation events in flowering plants and 7% in ferns. Speciation via polyploidy is likely to be one of the more predominant modes of sympatric speciation in plants, owing to its potentially broad-scale effects on gene regulation and developmental processes, effects that can produce immediate shifts in morphology, breeding system, and ecological tolerances. Theoretical models support the potential for increased adaptability in polyploid lineages. The evidence suggests that polyploidization can produce shifts in genetic systems and phenotypes that have the potential to result in increased evolutionary diversification, yet conclusive evidence that polyploidy has changed rates and patterns of diversification remains elusive.
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    Annual Review of Genetics 34 (2000), S. 233-254 
    ISSN: 0066-4197
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Coronary heart disease is a complex genetic disease with many genes involved, environmental influences, and important gene-environment interactions. This review discusses the genetic basis of the principal lipoprotein abnormalities associated with coronary heart disease susceptibility in the general population. Individual sections discuss genes regulating LDL cholesterol, HDL cholesterol, and triglyceride levels. A section is included on the effects of the common apo E genetic variation on lipoprotein levels, as well as sections on the genetic regulation of lipoprotein(a) levels, genes regulating the inverse relationship between triglyceride-rich lipoproteins and HDL cholesterol levels, and our current understanding of the genetic basis of familial combined hyperlipidemia. It is clear that the field has progressed, with early studies focused mainly on the association of candidate gene RFLPs with phenotypes, later studies of candidate genes in both parametric and nonparametric linkage studies, and now more and more studies combining linkage analysis with genome scans to identify new loci that influence lipoprotein phenotypes. The future should provide us with the capability to perform reasonable genetic profiling for lipoprotein abnormalities associated with coronary heart disease susceptibility.
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 79-111 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract We review the research on a wide variety of topics using data obtained with the 200-inch Hale telescope. Using state-of-the-art spectrographs, photometers, spectrometers and infrared detectors, the Palomar astronomers investigated the spectra of stars, interstellar matter, AGNs and quasars in great detail. Spectral resolutions ranged from 1000 A for broad-band photometry to 0.04 A using interferometric techniques.
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 231-288 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract Astronomical studies in the extreme ultraviolet (EUV) band of the spectrum were dismissed during the early years of space astronomy as impossible, primarily because of the mistaken view that radiation in this band would be absorbed by the interstellar medium. Observations in the 1980s from sounding rockets and limited duration orbital spacecraft began to show the potential of this field and led to the deployment of two spacecraft devoted to EUV astronomy: the UK Wide Field Camera and the Extreme Ultraviolet Explorer. The instrumentation in these missions, although quite limited in comparison with instrumentation in other fields of space astronomy, provided unique and far-reaching results. These included new information on solar system topics, stellar chromospheres and corona, white dwarf astrophysics, cataclysmic variables, the interstellar medium, galaxies, and clusters of galaxies. We summarize these findings herein.
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 573-611 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract This review emphasizes the mass loss processes that affect the fates of single stars with initial masses between one and nine solar masses. Just one epoch of mass loss has been clearly demonstrated to be important for these stars; that is the episode that ends their evolution up the asymptotic giant branch. Quite a clear picture of this evolutionary stage is emerging from current studies. Mass loss rates increase precipitously as stars evolve toward greater luminosity and radius and decreased effective temperature. As a result, empirical relationships between mass loss rates and stellar parameters are determined mostly by selection effects and tell us which stars are losing mass rather than how stars lose mass. After detailed theoretical models are found to match observational constraints, the models may be used to extrapolate to populations not available for study nearby, such as young stars with low metallicity. The fates of stars are found to depend on both their initial masses and their initial metallicities; a larger proportion of low-metallicity stars should end up with core masses reaching the Chandrasekhar limit, giving rise to Type 1.5 supernovae, and the remnant white dwarfs of low-Z populations will be both fewer and more massive than those in Population I. There are also clear indications that some stars lose one to several tenths of a solar mass during the helium core flash, but neither models nor observations reveal any details of this process yet. The observational and theoretical bases for a variety of mass loss formulae in current use are also reviewed in this article, and the relations are compared in a series of figures.
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 667-715 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract The Hubble space telescope observations of the northern Hubble deep field, and more recently its counterpart in the south, provide detections and photometry for stars and field galaxies to the faintest levels currently achievable, reaching magnitudes V~ 30. Since 1995, the northern Hubble deep field has been the focus of deep surveys at nearly all wavelengths. These observations have revealed many properties of high redshift galaxies and have contributed to important data on the stellar mass function in the Galactic halo.
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 521-571 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract Broad emission lines hold fundamental clues about the kinematics and structure of the central regions in AGN. In this article we review the most robust line profile properties and correlations emerging from the best data available. We identify fundamental differences between the profiles of radio-quiet and radio-loud sources as well as differences between the high- and low-ionization lines, especially in the radio-quiet majority of AGN. An Eigenvector 1 correlation space involving FWHM Hbeta, W(FeIIopt)/W(Hbeta), and the soft X-ray spectral index provides optimal discrimination between all principal AGN types (from narrow-line Seyfert 1 to radio galaxies). Both optical and radio continuum luminosities appear to be uncorrelated with the E1 parameters. We identify two populations of radio-quiet AGN: Population A sources (with FWHM(Hbeta) 4000 km s-1, generally strong FeII emission and a soft X-ray excess) show almost no parameter space overlap with radio-loud sources. Population B shows optical properties largely indistinguishable from radio-loud sources, including usually weak FeII emission, FWHM(Hbeta) 4000 km s-1 and lack of a soft X-ray excess. There is growing evidence that a fundamental parameter underlying Eigenvector 1 may be the luminosity-to-mass ratio of the active nucleus (L/M), with source orientation playing a concomitant role.
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    Annual Review of Astronomy and Astrophysics 38 (2000), S. 717-760 
    ISSN: 0066-4146
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Abstract The first millisecond X-ray variability phenomena from accreting compact objects have recently been discovered with the Rossi X-ray Timing Explorer. Three new phenomena are observed from low-mass X-ray binaries containing low-magnetic-field neutron stars: millisecond pulsations, burst oscillations, and kilohertz quasi-periodic oscillations. Models for these new phenomena involve the neutron star spin and orbital motion close around the neutron star, and rely explicitly on our understanding of strong gravity and dense matter. I review the observations of these new neutron-star phenomena and some possibly related phenomena in black-hole candidates, and describe the attempts to use these observations to perform measurements of fundamental physical interest in these systems.
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    Annual Review of Fluid Mechanics 32 (2000), S. 33-53 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Interest in novel forms of marine propulsion and maneuvering has sparked a number of studies on unsteadily operating propulsors. We review recent experimental and theoretical work identifying the principal mechanism for producing propulsive and transient forces in oscillating flexible bodies and fins in water, the formation and control of large-scale vortices. Connection with studies on live fish is made, explaining the observed outstanding fish agility.
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    Annual Review of Fluid Mechanics 32 (2000), S. 55-91 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Granular materials segregate. Small differences in either size or density lead to flow-induced segregation, a complex phenomenon without parallel in fluids. Modeling of mixing and segregation processes requires the confluence of several tools, including continuum and discrete descriptions (particle dynamics, Monte Carlo simulations, cellular automata computations) and, often, considerable geometrical insight. None of these viewpoints, however, is wholly satisfactory by itself. Moreover, continuum and discrete descriptions of granular flows are regime dependent, and this fact may require adopting different subviewpoints. This review organizes a body of knowledge that forms-albeit imperfectly-the beginnings of an expandable continuum framework for the description of mixing and segregation of granular materials. We focus primarily on noncohesive particles, possibly differing in size, density, shape, etc. We present segregation mechanisms and models for size and density segregation and introduce chaotic advection, which appears in noncircular tumblers. Chaotic advection interacts in nontrivial ways with segregation in granular materials and leads to unique equilibrium structures that serve as a prototype for systems displaying organization in the midst of disorder.
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