bluuebunny/crossref_metadata_2025 huggingface dataset:
History and Anthropology in South Asia: Rethinking the Archive
Authors: Mathur Saloni
Published: July 2002

▪ Abstract  This article examines the relationship between history and anthropology in South Asia during the past two decades, a relationship that has done much to shape the emerging intellectual practices of postcolonial anthropology. After locating the current conjuncture in an earlier moment of American anthropology in South Asia—village studies of the 1950s—the article reviews a body of interdisciplinary scholarship published during the 1980s and 1990s, paying specific attention to the impact of debates in Indian historiography generated by subaltern studies. The article goes on to identify five interlinked sets of themes in the literature for discussion: the “problem” of Europe, the interpenetration of power and knowledge in the colonial archive, the search for indigenous forms of knowledge, the phenomenon of violence and ethnic conflict, and the specific concerns of gender and feminist criticism. It argues that it is no longer feasible to do anthropology in South Asia without attending to one or more of these five themes. Any concern with contemporary transnational or cultural configurations in South Asia, or with the future of the postcolonial nation state, must be considered in relation to colonial history and the specific formations of modernity it generated.
AIDS and Criminal Justice
Authors: Kane Stephanie , Mason Theresa
Published: July 2002

▪ Abstract  This article reviews scholarship at the intersection of anthropology, criminal justice, and AIDS. Street ethnography is presented in a political and historical context, focusing on the distinctive ways that anthropologists have contributed to discussions of illegal drug and sex markets in poor urban neighborhoods. The review also considers subjects that may be explored by anthropologists in the future, including imprisonment as an institutional HIV risk factor that intensifies individual behavioral risk and the criminalization of intentional HIV transmission. This research area raises critical questions about how culture and law shape viral risk.
DIOXYGENASES: Molecular Structure and Role in Plant Metabolism
Authors: Prescott Andy G. , John Philip
Published: July 2002

▪ Abstract  Dioxygenases are nonheme iron-containing enzymes important in the biosynthesis of plant signaling compounds such as abscisic acid, gibberellins, and ethylene and also of secondary metabolites, notably flavonoids and alkaloids. Plant dioxygenases fall into two classes: lipoxygenases and 2-oxoacid-dependent dioxygenases. The latter catalyze hydroxylation, epoxidation, and desaturation reactions; some enzymes catalyze more than one type of reaction in successive steps in a biosynthetic pathway. This review highlights recent discoveries on both enzyme groups, particularly in relation to gibberellin biosynthesis, in vivo activity of 1-aminocyclopropane-1-carboxylate oxidase, and molecular structure/function relationships. Similarities between the roles of monooxygenases and dioxygenases are also discussed.
AUXIN BIOSYNTHESIS
Authors: Bartel Bonnie
Published: July 2002

▪ Abstract  Indole-3-acetic acid (IAA) is the most abundant naturally occurring auxin. Plants produce active IAA both by de novo synthesis and by releasing IAA from conjugates. This review emphasizes recent genetic experiments and complementary biochemical analyses that are beginning to unravel the complexities of IAA biosynthesis in plants. Multiple pathways exist for de novo IAA synthesis in plants, and a number of plant enzymes can liberate IAA from conjugates. This multiplicity has contributed to the current situation in which no pathway of IAA biosynthesis in plants has been unequivocally established. Genetic and biochemical experiments have demonstrated both tryptophan-dependent and tryptophan-independent routes of IAA biosynthesis. The recent application of precise and sensitive methods for quantitation of IAA and its metabolites to plant mutants disrupted in various aspects of IAA regulation is beginning to elucidate the multiple pathways that control IAA levels in the plant.
CALMODULIN AND CALMODULIN-BINDING PROTEINS IN PLANTS
Authors: Zielinski Raymond E.
Published: July 2002

▪ Abstract  Calmodulin is a small Ca2+-binding protein that acts to transduce second messenger signals into a wide array of cellular responses. Plant calmodulins share many structural and functional features with their homologs from animals and yeast, but the expression of multiple protein isoforms appears to be a distinctive feature of higher plants. Calmodulin acts by binding to short peptide sequences within target proteins, thereby inducing structural changes, which alters their activities in response to changes in intracellular Ca2+concentration. The spectrum of plant calmodulin-binding proteins shares some overlap with that found in animals, but a growing number of calmodulin-regulated proteins in plants appear to be unique. Ca2+-binding and enzymatic activation properties of calmodulin are discussed emphasizing the functional linkages between these processes and the diverse pathways that are dependent on Ca2+signaling.
CO2 CONCENTRATING MECHANISMS IN PHOTOSYNTHETIC MICROORGANISMS
Authors: Kaplan Aaron , Reinhold Leonora
Published: July 2002

▪ Abstract  Many microorganisms possess inducible mechanisms that concentrate CO2 at the carboxylation site, compensating for the relatively low affinity of Rubisco for its substrate, and allowing acclimation to a wide range of CO2 concentrations. The organization of the carboxysomes in prokaryotes and of the pyrenoids in eukaryotes, and the presence of membrane mechanisms for inorganic carbon (Ci) transport, are central to the concentrating mechanism. The presence of multiple Ci transporting systems in cyanobacteria has been indicated. Certain genes involved in structural organization, Ci transport and the energization of the latter have been identified. Massive Ci fluxes associated with the CO2-concentrating mechanism have wide-reaching ecological and geochemical implications.
PLANT COLD ACCLIMATION: Freezing Tolerance Genes and Regulatory Mechanisms
Authors: Thomashow Michael F.
Published: July 2002

▪ Abstract  Many plants increase in freezing tolerance upon exposure to low nonfreezing temperatures, a phenomenon known as cold acclimation. In this review, recent advances in determining the nature and function of genes with roles in freezing tolerance and the mechanisms involved in low temperature gene regulation and signal transduction are described. One of the important conclusions to emerge from these studies is that cold acclimation includes the expression of certain cold-induced genes that function to stabilize membranes against freeze-induced injury. In addition, a family of Arabidopsis transcription factors, the CBF/DREB1 proteins, have been identified that control the expression of a regulon of cold-induced genes that increase plant freezing tolerance. These results along with many of the others summarized here further our understanding of the basic mechanisms that plants have evolved to survive freezing temperatures. In addition, the findings have potential practical applications as freezing temperatures are a major factor limiting the geographical locations suitable for growing crop and horticultural plants and periodically account for significant losses in plant productivity.
DIVERSITY AND REGULATION OF PLANT Ca2+ PUMPS: Insights from Expression in Yeast
Authors: Sze Heven , Liang Feng , Hwang Ildoo , Curran Amy C. , Harper Jeffrey F.
Published: July 2002

▪ Abstract  The spatial and temporal regulation of calcium concentration in plant cells depends on the coordinate activities of channels and active transporters located on different organelles and membranes. Several Ca2+ pumps have been identified and characterized by functional expression of plant genes in a yeast mutant (K616). This expression system has opened the way to a genetic and biochemical characterization of the regulatory and catalytic features of diverse Ca2+ pumps. Plant Ca2+-ATPases fall into two major types: AtECA1 represents one of four or more members of the type IIA (ER-type) Ca2+-ATPases in Arabidopsis, and AtACA2 is one of seven or more members of the type IIB (PM-type) Ca2+-ATPases that are regulated by a novel amino terminal domain. Type IIB pumps are widely distributed on membranes, including the PM (plasma membrane), vacuole, and ER (endoplasmic reticulum). The regulatory domain serves multiple functions, including autoinhibition, calmodulin binding, and sites for modification by phosphorylation. This domain, however, is considerably diverse among several type IIB ATPases, suggesting that the pumps are differentially regulated. Understanding of Ca2+ transporters at the molecular level is providing insights into their roles in signaling networks and in regulating fundamental processes of cell biology.
THE FU ORIONIS PHENOMENON
Authors: Hartmann Lee , Kenyon Scott J.
Published: July 2002

▪ Abstract  We summarize the properties of FU Orionis variables, and show how accretion disk models simply explain many peculiarities of these objects. FU Ori systems demonstrate that disk accretion in early stellar evolution is highly episodic, varying from ∼ 10−7[Formula: see text] yr−1 in the low (T Tauri) state to 10−4 [Formula: see text] yr−1 in the high (FU Ori) state. This variability in mass accretion is matched by a corresponding variability in mass ejection, with mass loss rates reaching ∼ 10−1 of the mass accretion rates in outburst. It appears that the FU Ori phenomenon is restricted to early phases of stellar evolution, probably with infall still occuring to the disk, which may help drive repetitive outbursts. Thermal instabilities are a promising way to produce FU Ori disk outbursts, although many uncertainties remain in the theory; triggering by interactions with companion stars on eccentric orbits may also play a role.
THE SUN'S VARIABLE RADIATION AND ITS RELEVANCE FOR EARTH
Authors: Lean Judith
Published: July 2002

▪ Abstract  To what extent are changes in the Earth's global environment linked with fluctuations in its primary energy source, the radiation from a variable star, the Sun? A firm scientific basis for policy making with regard to anthropogenic greenhouse warming of climate and chlorofluorocarbon depletion of ozone requires a reliable answer to this question. Reduction of the vulnerability of spacecraft operations and communications to space weather necessitates knowledge of solar induced variability in Earth's upper atmosphere. Toward these goals, solar radiation monitoring and studies of solar variability mechanisms facilitate an understanding of the sources and amplitudes of the Sun's changing radiation. Interdisciplinary studies that link these changes with a wide array of terrestrial phenomena over the longer time scales of global change and the shorter time scales of space weather address the relevance of solar radiation variability for Earth. However, although numerous associations are apparent between solar and terrestrial fluctuations, full comprehension of the physical mechanisms responsible for the many facets of radiative Sun-Earth coupling remains to be accomplished.
FAINT BLUE GALAXIES
Authors: Ellis Richard S.
Published: July 2002

▪ Abstract  The physical properties of the faint blue galaxy population are reviewed in the context of observational progress made via deep spectroscopic surveys and Hubble Space Telescope imaging of field galaxies at various limits and theoretical models for the integrated star formation history of the universe. Notwithstanding uncertainties in the properties of the local population of galaxies, convincing evidence has emerged from several independent studies for a rapid decline in the volume-averaged star-formation rate of field galaxies since a redshift z ≈ 1. Together with the small angular sizes and modest mean redshift of the faintest detectable sources, these results can be understood in hierarchical models where the bulk of the star formation occurred at redshifts between z ≈ 1−2. The physical processes responsible for the subsequent demise of the faint blue galaxy population remain unclear. Considerable progress will be possible when the evolutionary trends can be monitored in the context of independent physical parameters such as the underlying galactic mass.
CHEMICAL EVOLUTION OF STAR-FORMING REGIONS
Authors: van Dishoeck Ewine F. , Blake Geoffrey A.
Published: July 2002

▪ Abstract  Recent advances in the understanding of the chemical processes that occur during all stages of the formation of stars, from the collapse of molecular clouds to the assemblage of icy planetesimals in protoplanetary accretion disks, are reviewed. Observational studies of the circumstellar material within 100–10,000 AU of the young star with (sub)millimeter single-dish telescopes, millimeter interferometers, and ground-based as well as space-borne infrared observatories have only become possible within the past few years. Results are compared with detailed chemical models that emphasize the coupling of gas-phase and grain-surface chemistry. Molecules that are particularly sensitive to different routes of formation and that may be useful in distinguishing between a variety of environments and histories are outlined. In the cold, low-density prestellar cores, radicals and long unsaturated carbon chains are enhanced. During the cold collapse phase, most species freeze out onto the grains in the high-density inner region. Once young stars ignite, their surroundings are heated through radiation and/or shocks, whereupon new chemical characteristics appear. Evaporation of ices drives a “hot core” chemistry rich in organic molecules, whereas shocks propagating through the dense envelope release both refractory and volatile grain material, resulting in prominent SiO, OH, and H2O emission. The role of future instrumentation in further developing these chemical and temporal diagnostics is discussed.
Probing the Universe with Weak Lensing
Authors: Mellier Yannick
Published: July 2002

▪ Abstract  Gravitational lenses can provide crucial information on the geometry of the Universe, on the cosmological scenario of formation of its structures as well as on the history of its components with look-back time. In this review, I focus on the most recent results obtained during the last five years from the analysis of the weak lensing regime. The potential of weak lensing as a probe of dark matter and the study of the coupling between light and mass on scales of clusters of galaxies, large-scale structures and galaxies is discussed first. Then I present the impact of weak lensing for the study of distant galaxies and of the population of lensed sources as a function of redshift. Finally, I discuss the potential of weak lensing to constrain the cosmological parameters, either from pure geometrical effects observed in peculiar lenses, or from the coupling of weak lensing with the CMB.
Organic Molecules in the Interstellar Medium, Comets, and Meteorites: A Voyage from Dark Clouds to the Early Earth
Authors: Ehrenfreund Pascale , Charnley Steven B.
Published: July 2002

▪ 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 Å, 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.
The Development of High-Resolution Imaging in Radio Astronomy
Authors: Kellermann K. I. , Moran J. M.
Published: July 2002

▪ Abstract  Since the first radio astronomy observations in the 1930s, the angular resolution of radio telescopes has improved from tens of degrees to better than one thousandth of a second of arc. This advancement has been the result of technological innovations such as stable, sensitive, short-wavelength radio receivers, digital correlators, atomic clocks, and high-speed tape recorders, as well as the development of sophisticated image processing algorithms implemented on inexpensive, fast, digital computers.
MOLECULAR BASIS FOR MEMBRANE PHOSPHOLIPID DIVERSITY: Why Are There So Many Lipids?
Authors: Dowhan W.
Published: July 2002

Phospholipids play multiple roles in cells by establishing the permeability barrier for cells and cell organelles, by providing the matrix for the assembly and function of a wide variety of catalytic processes, by acting as donors in the synthesis of macromolecules, and by actively influencing the functional properties of membrane-associated processes. The function, at the molecular level, of phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin in specific cellular processes is reviewed, with a focus on the results of combined molecular genetic and biochemical studies in Escherichia coli. These results are compared with primarily biochemical data supporting similar functions for these phospholipids in eukaryotic organisms. The wide range of processes in which specific involvement of phospholipids has been documented explains the need for diversity in phospholipid structure and why there are so many membrane lipids.
RIBOSOMES AND TRANSLATION
Authors: Green Rachel , Noller Harry F.
Published: July 2002

The ribosome is a large multifunctional complex composed of both RNA and proteins. Biophysical methods are yielding low-resolution structures of the overall architecture of ribosomes, and high-resolution structures of individual proteins and segments of rRNA. Accumulating evidence suggests that the ribosomal RNAs play central roles in the critical ribosomal functions of tRNA selection and binding, translocation, and peptidyl transferase. Biochemical and genetic approaches have identified specific functional interactions involving conserved nucleotides in 16S and 23S rRNA. The results obtained by these quite different approaches have begun to converge and promise to yield an unprecedented view of the mechanism of translation in the coming years.
TRANSCRIPTIONAL REGULATION BY CYCLIC AMP
Authors: Montminy Marc
Published: July 2002

A number of hormones and growth factors have been shown to stimulate target cells via second messenger pathways that in turn regulate the phosphorylation of specific nuclear factors. The second messenger cyclic AMP, for example, regulates a striking number of physiologic processes, including intermediary metabolism, cellular proliferation, and neuronal signaling, by altering basic patterns of gene expression.

Our understanding of cyclic AMP signaling in the nucleus has expanded considerably over the past decade, owing in large part to the characterization of cyclic AMP–responsive promoter elements, transcription factors that bind them, and signal-dependent coactivators that mediate target gene induction. More importantly, these studies have revealed new insights into biological problems as diverse as biological clocks and long-term memory. The purpose of this review is to describe the components of the cyclic AMP response unit and to analyze how these components cooperate to induce target gene expression in response to hormonal stimulation.
THE GREEN FLUORESCENT PROTEIN
Authors: Tsien Roger Y.
Published: July 2002

In just three years, the green fluorescent protein (GFP) from the jellyfish Aequorea victoria has vaulted from obscurity to become one of the most widely studied and exploited proteins in biochemistry and cell biology. Its amazing ability to generate a highly visible, efficiently emitting internal fluorophore is both intrinsically fascinating and tremendously valuable. High-resolution crystal structures of GFP offer unprecedented opportunities to understand and manipulate the relation between protein structure and spectroscopic function. GFP has become well established as a marker of gene expression and protein targeting in intact cells and organisms. Mutagenesis and engineering of GFP into chimeric proteins are opening new vistas in physiological indicators, biosensors, and photochemical memories.
Protein Tyrosine Kinase Structure and Function
Authors: Hubbard Stevan R. , Till Jeffrey H.
Published: July 2002

▪ Abstract  Tyrosine phosphorylation is one of the key covalent modifications that occurs in multicellular organisms as a result of intercellular communication during embryogenesis and maintenance of adult tissues. The enzymes that carry out this modification are the protein tyrosine kinases (PTKs), which catalyze the transfer of the γ phosphate of ATP to tyrosine residues on protein substrates. Phosphorylation of tyrosine residues modulates enzymatic activity and creates binding sites for the recruitment of downstream signaling proteins. Two classes of PTKs are present in cells: the transmembrane receptor PTKs and the nonreceptor PTKs. Because PTKs are critical components of cellular signaling pathways, their catalytic activity is strictly regulated. Over the past several years, high-resolution structural studies of PTKs have provided a molecular basis for understanding the mechanisms by which receptor and nonreceptor PTKs are regulated. This review will highlight the important results that have emerged from these structural studies.
Clathrin
Authors: Kirchhausen Tomas
Published: July 2002

▪ Abstract  Clathrin was discovered nearly 25 years ago. Since then, a large number of other proteins that participate in the process by which clathrin-coated vesicles retrieve synaptic membranes or take up endocytic receptors have been identified. The functional relationships among these disparate components remain, in many cases, obscure. High-resolution structures of parts of clathrin, determined by X-ray crystallography, and lower-resolution images of assembled coats, determined by electron cryomicroscopy, now provide the information necessary to integrate various lines of evidence and to design experiments that test specific mechanistic notions. This review summarizes and illustrates the recent structural results and outlines what is known about coated-vesicle assembly in the context of this information.
PTEN and Myotubularin: Novel Phosphoinositide Phosphatases
Authors: Maehama Tomohiko , Taylor Gregory S. , Dixon Jack E.
Published: July 2002

▪ Abstract  Protein tyrosine phosphatases (PTPs) are a diverse group of enzymes that contain a highly conserved active site motif, Cys-x5-Arg (Cx5R). The PTP super-family enzymes, which include tyrosine-specific, dual specificity, low-molecular-weight, and Cdc25 phosphatases, are key mediators of a wide variety of cellular processes, including growth, metabolism, differentiation, motility, and programmed cell death. The PTEN/MMAC1/TEP1 gene was originally identified as a candidate tumor suppressor gene located on human chromosome 10q23; it encodes a protein with sequence similarity to PTPs and tensin. Recent studies have demonstrated that PTEN plays an essential role in regulating signaling pathways involved in cell growth and apoptosis, and mutations in the PTEN gene are now known to cause tumorigenesis in a number of human tissues. In addition, germ line mutations in the PTEN gene also play a major role in the development of Cowden and Bannayan-Zonana syndromes, in which patients often suffer from increased risk of breast and thyroid cancers. Biochemical studies of the PTEN phosphatase have revealed a molecular mechanism by which tumorigenesis may be caused in individuals with PTEN mutations. Unlike most members of the PTP superfamily, PTEN utilizes the phosphoinositide second messenger, phosphatidylinositol 3,4,5-trisphosphate (PIP3), as its physiologic substrate. This inositol lipid is an important regulator of cell growth and survival signaling through the Ser/Thr protein kinases PDK1 and Akt. By specifically dephosphorylating the D3 position of PIP3, the PTEN tumor suppressor functions as a negative regulator of signaling processes downstream of this lipid second messenger. Mutations that impair PTEN function result in a marked increase in cellular levels of PIP3 and constitutive activation of Akt survival signaling pathways, leading to inhibition of apoptosis, hyperplasia, and tumor formation. Certain structural features of PTEN contribute to its specificity for PIP3, as well as its role(s) in regulating cellular proliferation and apoptosis. Recently, myotubularin, a second PTP superfamily enzyme associated with human disease, has also been shown to utilize a phosphoinositide as its physiologic substrate.
Synthesis and Function of 3-Phosphorylated Inositol Lipids
Authors: Vanhaesebroeck Bart , Leevers Sally J. , Ahmadi Khatereh , Timms John , Katso Roy , Driscoll Paul C. , Woscholski Rudiger , Parker Peter J. , Waterfield Michael D.
Published: July 2002

▪ Abstract  The 3-phosphorylated inositol lipids fulfill roles as second messengers by interacting with the lipid binding domains of a variety of cellular proteins. Such interactions can affect the subcellular localization and aggregation of target proteins, and through allosteric effects, their activity. Generation of 3-phosphoinositides has been documented to influence diverse cellular pathways and hence alter a spectrum of fundamental cellular activities. This review is focused on the 3-phosphoinositide lipids, the synthesis of which is acutely triggered by extracellular stimuli, the enzymes responsible for their synthesis and metabolism, and their cell biological roles. Much knowledge has recently been gained through structural insights into the lipid kinases, their interaction with inhibitors, and the way their 3-phosphoinositide products interact with protein targets. This field is now moving toward a genetic dissection of 3-phosphoinositide action in a variety of model organisms. Such approaches will reveal the true role of the 3-phosphoinositides at the organismal level in health and disease.
Regulation of G Protein–Initiated Signal Transduction in Yeast: Paradigms and Principles
Authors: Dohlman Henrik G. , Thorner Jeremy
Published: July 2002

▪ Abstract  All cells have the capacity to evoke appropriate and measured responses to signal molecules (such as peptide hormones), environmental changes, and other external stimuli. Tremendous progress has been made in identifying the proteins that mediate cellular response to such signals and in elucidating how events at the cell surface are linked to subsequent biochemical changes in the cytoplasm and nucleus. An emerging area of investigation concerns how signaling components are assembled and regulated (both spatially and temporally), so as to control properly the specificity and intensity of a given signaling pathway. A related question under intensive study is how the action of an individual signaling pathway is integrated with (or insulated from) other pathways to constitute larger networks that control overall cell behavior appropriately. This review describes the signal transduction pathway used by budding yeast (Saccharomyces cerevisiae) to respond to its peptide mating pheromones. This pathway is comprised by receptors, a heterotrimeric G protein, and a protein kinase cascade all remarkably similar to counterparts in multicellular organisms. The primary focus of this review, however, is recent advances that have been made, using primarily genetic methods, in identifying molecules responsible for regulation of the action of the components of this signaling pathway. Just as many of the constituent proteins of this pathway and their interrelationships were first identified in yeast, the functions of some of these regulators have clearly been conserved in metazoans, and others will likely serve as additional models for molecules that carry out analogous roles in higher organisms.
Histone Acetyltransferases
Authors: Roth Sharon Y. , Denu John M. , Allis C. David
Published: July 2002

▪ Abstract  Transcriptional regulation in eukaryotes occurs within a chromatin setting and is strongly influenced by nucleosomal barriers imposed by histone proteins. Among the well-known covalent modifications of histones, the reversible acetylation of internal lysine residues in histone amino-terminal domains has long been positively linked to transcriptional activation. Recent biochemical and genetic studies have identified several large, multisubunit enzyme complexes responsible for bringing about the targeted acetylation of histones and other factors. This review discusses our current understanding of histone acetyltransferases (HATs) or acetyltransferases (ATs): their discovery, substrate specificity, catalytic mechanism, regulation, and functional links to transcription, as well as to other chromatin-modifying activities. Recent studies underscore unexpected connections to both cellular regulatory processes underlying normal development and differentiation, as well as abnormal processes that lead to oncogenesis. Although the functions of HATs and the mechanisms by which they are regulated are only beginning to be understood, these fundamental processes are likely to have far-reaching implications for human biology and disease.
Microfabrication in Biology and Medicine
Authors: Voldman Joel , Gray Martha L. , Schmidt Martin A.
Published: July 2002

▪ Abstract  Microfabrication uses integrated-circuit manufacturing technology supplemented by its own processes to create objects with dimensions in the range of micrometers to millimeters. These objects can have miniature moving parts, stationary structures, or both. Microfabrication has been used for many applications in biology and medicine. These applications fall into four domains: tools for molecular biology and biochemistry, tools for cell biology, medical devices, and biosensors. Microfabricated device structures may provide significantly enhanced function with respect to a conventional device. Sometimes microfabrication can enable devices with novel capabilities. These enhancing and enabling qualities are conferred when microfabrication is used appropriately to address the right types of problems.

Herein, we describe microfabrication technology and its application to biology and medicine. We detail several classes of advantages conferred by microfabrication and how these advantages have been used to date.
Microfabricated Microneedles for Gene and Drug Delivery
Authors: McAllister Devin V. , Allen Mark G. , Prausnitz Mark R.
Published: July 2002

▪ Abstract  By incorporating techniques adapted from the microelectronics industry, the field of microfabrication has allowed the creation of microneedles, which have the potential to improve existing biological-laboratory and medical devices and to enable novel devices for gene and drug delivery. Dense arrays of microneedles have been used to deliver DNA into cells. Many cells are treated at once, which is much more efficient than current microinjection techniques. Microneedles have also been used to deliver drugs into local regions of tissue. Microfabricated neural probes have delivered drugs into neural tissue while simultaneously stimulating and recording neuronal activity, and microneedles have been inserted into arterial vessel walls to deliver antirestenosis drugs. Finally, microhypodermic needles and microneedles for transdermal drug delivery have been developed to reduce needle insertion pain and tissue trauma and to provide controlled delivery across the skin. These needles have been shown to be robust enough to penetrate skin and dramatically increase skin permeability to macromolecules.
ADVANCED EPR SPECTROSCOPY ON ELECTRON TRANSFER PROCESSES IN PHOTOSYNTHESIS AND BIOMIMETIC MODEL SYSTEMS
Authors: Levanon H. , Möbius K.
Published: July 2002

▪ Abstract  This review focuses on the recent advances in EPR spectroscopy as they are applied both to photoinduced electron transfer in the photosynthetic apparatus and to biomimetic systems. The review deals with time-resolved direct-detection cw and pulsed EPR and ENDOR methods, both at conventional bands [X-(9.5 GHz), K-(24 GHz), and Q-(35 GHz)] and at high frequency bands (W-band, 95 GHz, and even highter frequency bands). EPR studies on photosynthetic and model systems in their doublet, triplet and radical pair states are surveyed, including their static and dynamic properties. Applications of time-resolved EPR in studying photoinduced electron and energy transfer in isotropic and anisotropic environments, and the concepts of electron spin polarization and magnetic field effects in photochemical reactions are also reviewed.
BIOSENSORS IN CHEMICAL SEPARATIONS
Authors: Fishman Harvey A. , Greenwald Daniel R. , Zare Richard N.
Published: July 2002

▪ Abstract  Identification of biomolecules in complex biological mixtures represents a major challenge in biomedical, environmental, and chemical research today. Chemical separations with traditional detection schemes such as absorption, fluorescence, refractive index, conductivity, and electrochemistry have been the standards for definitive identifications of many compounds. In many instances, however, the complexity of the biomixture exceeds the resolution capability of chemical separations. Biosensors based on molecular recognition can dramatically improve the selectivity of and provide biologically relevant information about the components. This review describes how coupling chemical separations with online biosensors solves challenging problems in sample analysis by identifying components that would not normally be detectable by either technique alone. This review also presents examples and principles of combining chemical separations with biosensor detection that uses living systems, whole cells, membrane receptors, enzymes, and immunosensors.
DNA NANOTECHNOLOGY: Novel DNA Constructions
Authors: Seeman Nadrian C.
Published: July 2002

▪ Abstract  DNA nanotechnology entails the construction of specific geometrical and topological targets from DNA. The goals include the use of DNA molecules to scaffold the assembly of other molecules, particularly in periodic arrays, with the objects of both crystal facilitation and memory-device construction. Many of these products are based on branched DNA motifs. DNA molecules with the connectivities of a cube and a truncated octahedron have been prepared. A solid-support methodology has been developed to construct DNA targets. DNA trefoil and figure-8 knots have been made, predicated on the relationship between a topological crossing and a half-turn of B-DNA or Z-DNA. The same basis has been used to construct Borromean rings from DNA. An RNA knot has been used to demonstrate an RNA topoisomerase activity. The desire to construct periodic matter held together by DNA sticky ends has resulted in a search for stiff components; DNA double crossover molecules appear to be the best candidates. It appears that novel DNA motifs may be of use in the new field of DNA-based computing.
INHIBITORS OF HIV-1 PROTEASE: A Major Success of Structure-Assisted Drug Design
Authors: Wlodawer Alexander , Vondrasek Jiri
Published: July 2002

▪ Abstract  Retroviral protease (PR) from the human immunodeficiency virus type 1 (HIV-1) was identified over a decade ago as a potential target for structure-based drug design. This effort was very successful. Four drugs are already approved, and others are undergoing clinical trials. The techniques utilized in this remarkable example of structure-assisted drug design included crystallography, NMR, computational studies, and advanced chemical synthesis. The development of these drugs is discussed in detail. Other approaches to designing HIV-1 PR inhibitors, based on the concepts of symmetry and on the replacement of a water molecule that had been found tetrahedrally coordinated between the enzyme and the inhibitors, are also discussed. The emergence of drug-induced mutations of HIV-1 PR leads to rapid loss of potency of the existing drugs and to the need to continue the development process. The structural basis of drug resistance and the ways of overcoming this phenomenon are mentioned.
Binding of Ligands and Activation of Transcription by Nuclear Receptors
Authors: Steinmetz Anke C. U. , Renaud Jean-Paul , Moras Dino
Published: July 2002

▪ Abstract  Nuclear receptors (NRs) form a superfamily of ligand-inducible transcription factors composed of several domains. Recent structural studies focused on domain E, which harbors the ligand-binding site and the ligand-dependent transcription activation function AF-2. Structures of single representatives in an increasing number of various complexes as well as new structures of further NRs addressed issues such as discrimination of ligands, superagonism, isotype specificity, and partial agonism. Until today, one unique transcriptionally active form of domain E was determined; however, divergent tertiary structures of apo-forms and transcriptionally inactive forms are known. Thus, recent results link the transformation of NRs upon ligand binding to principles of protein folding. Furthermore, the ensemble of NR structures, including those of DNA-binding domains, provides one of the foundations for the understanding of interactions with transcription intermediary factors up to the characterization of the link between NR complexes and the basal transcriptional machinery at the structural level.
Mass Spectrometry as a Tool for Protein Crystallography
Authors: Cohen Steven L. , Chait Brian T.
Published: July 2002

▪ Abstract  Atomic resolution structure determinations of proteins by X-ray crystallography are formidable multidisciplinary undertakings, requiring protein construct design, expression and purification, crystallization trials, phase determination, and model building. Modern mass spectrometric methods can greatly facilitate these obligate tasks. Thus, mass spectrometry can be used to verify that the desired protein construct has been correctly expressed, to define compact domains in the target protein, to assess the components contained within the protein crystals, and to screen for successful incorporation of seleno-methionine and other heavy metal reagents used for phasing. In addition, mass spectrometry can be used to address issues of modeling, topology, and side-chain proximity. Here, we demonstrate how rational use of mass spectrometry assists and expedites high resolution X-ray structure determination through each stage of the process of protein crystallography.
THE MAMMALIAN MYOSIN HEAVY CHAIN GENE FAMILY
Authors: Weiss Allison , Leinwand Leslie A.
Published: July 2002

▪ Abstract  Myosin is a highly conserved, ubiquitous protein found in all eukaryotic cells, where it provides the motor function for diverse movements such as cytokinesis, phagocytosis, and muscle contraction. All myosins contain an amino-terminal motor/head domain and a carboxy-terminal tail domain. Due to the extensive number of different molecules identified to date, myosins have been divided into seven distinct classes based on the properties of the head domain. One such class, class II myosins, consists of the conventional two-headed myosins that form filaments and are composed of two myosin heavy chain (MYH) subunits and four myosin light chain subunits. The MYH subunit contains the ATPase activity providing energy that is the driving force for contractile processes mentioned above, and numerous MYH isoforms exist in vertebrates to carry out this function. The MYHs involved in striated muscle contraction in mammals are the focus of the current review. The genetics, molecular biology, and biochemical properties of mammalian MYHs are discussed below. MYH gene expression patterns in developing and adult striated muscles are described in detail, as are studies of regulation of MYH genes in the heart. The discovery that mutant MYH isoforms have a causal role in the human disease familial hypertrophic cardiomyopathy (FHC) has implemented structure/function investigations of MYHs. The regulation of MYH genes expressed in skeletal muscle and the potential functional implications that distinct MYH isoforms may have on muscle physiology are addressed.
INTRACELLULAR PATHOGENS AND THE ACTIN CYTOSKELETON
Authors: Dramsi S. , Cossart P.
Published: July 2002

▪ Abstract  Many pathogens actively exploit the actin cytoskeleton during infection. This exploitation may take place during entry into mammalian cells after engagement of a receptor and/or as series of signaling events culminating in the engulfment of the microorganism. Although actin rearrangements are a common feature of most internalization events (e.g. entry of Listeria, Salmonella, Shigella, Yersinia, Neisseria, and Bartonella), bacterial and other cellular factors involved in entry are specific to each bacterium. Another step during which pathogens harness the actin cytoskeleton takes place in the cytosol, within which some bacteria (Listeria, Shigella, Rickettsia) or viruses (vaccinia virus) are able to move. Movement is coupled to a polarized actin polymerization process, with the formation of characteristic actin tails. Increasing attention has focused on this phenomenon due to its striking similarity to cellular events occurring at the leading edge of locomoting cells. Thus pathogens are convenient systems in which to study actin cytoskeleton rearrangements in response to stimuli at the plasma membrane or inside cells.
DEFINING ACTIN FILAMENT LENGTH IN STRIATED MUSCLE: Rulers and Caps or Dynamic Stability?
Authors: Littlefield R. , Fowler V. M.
Published: July 2002

▪ Abstract  Actin filaments (thin filaments) are polymerized to strikingly uniform lengths in striated muscle sarcomeres. Yet, actin monomers can exchange dynamically into thin filaments in vivo, indicating that actin monomer association and dissociation at filament ends must be highly regulated to maintain the uniformity of filament lengths. We propose several hypothetical mechanisms that could generate uniform actin filament length distributions and discuss their application to the determination of thin filament length in vivo. At the Z line, titin may determine the minimum extent and tropomyosin the maximum extent of thin filament overlap by regulating α-actinin binding to actin, while a unique Z filament may bind to capZ and regulate barbed end capping. For the free portion of the thin filament, we evaluate possibilities that thin filament components (e.g. nebulin or the tropomyosin/troponin polymer) determine thin filament lengths by binding directly to tropomodulin and regulating pointed end capping, or alternatively, that myosin thick filaments, together with titin, determine filament length by indirectly regulating tropomodulin's capping activity.
Cellular Signaling and Volume Control in Stomatal Movements in Plants
Authors: Blatt Michael R.
Published: July 2002

▪ 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.
Plasmodesmata: Gatekeepers for Cell-to-Cell Transport of Developmental Signals in Plants
Authors: Zambryski Patricia , Crawford Katrina
Published: July 2002

▪ 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.
Dynamin and Its Role in Membrane Fission
Authors: Hinshaw J. E.
Published: July 2002

▪ 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.