Showing papers by "State University of New York System published in 1999"

The meta-analysis of response ratios in experimental ecology

Abstract: Meta-analysis provides formal statistical techniques for summarizing the results of independent experiments and is increasingly being used in ecology. The response ratio (the ratio of mean outcome in the experimental group to that in the control group) and closely related measures of proportionate change are often used as measures of effect magnitude in ecology. Using these metrics for meta-analysis requires knowledge of their statistical properties, but these have not been previously derived. We give the approximate sampling distribution of the log response ratio, discuss why it is a particularly useful metric for many applications in ecology, and demonstrate how to use it in meta-analysis. The meta-analysis of response-ratio data is illustrated using experimental data on the effects of increased atmospheric CO2 on plant biomass responses.

Impact: Toward a Framework for Understanding the Ecological Effects of Invaders

Abstract: Although ecologists commonly talk about the impacts of nonindigenous species, little formal attention has been given to defining what we mean by impact, or connecting ecological theory with particular measures of impact. The resulting lack of generalizations regarding invasion impacts is more than an academic problem; we need to be able to distinguish invaders with minor effects from those with large effects in order to prioritize management efforts. This paper focuses on defining, evaluating, and comparing a variety of measures of impact drawn from empirical examples and theoretical reasoning. We begin by arguing that the total impact of an invader includes three fundamental dimensions: range, abundance, and the per-capita or per-biomass effect of the invader. Then we summarize previous approaches to measuring impact at different organizational levels, and suggest some new approaches. Reviewing mathematical models of impact, we argue that theoretical studies using community assembly models could act as a basis for better empirical studies and monitoring programs, as well as provide a clearer understanding of the relationship among different types of impact. We then discuss some of the particular challenges that come from the need to prioritize invasive species in a management or policy context. We end with recommendations about how the field of invasion biology might proceed in order to build a general framework for understanding and predicting impacts. In particular, we advocate studies designed to explore the correlations among different measures: Are the results of complex multivariate methods adequately captured by simple composite metrics such as species richness? How well are impacts on native populations correlated with impacts on ecosystem functions? Are there useful bioindicators for invasion impacts? To what extent does the impact of an invasive species depend on the system in which it is measured? Three approaches would provide new insights in this line of inquiry: (1) studies that measure impacts at multiple scales and multiple levels of organization, (2) studies that synthesize currently available data on different response variables, and (3) models designed to guide empirical work and explore generalities.

Extending the methodology of X-ray crystallography to allow imaging of micrometre-sized non-crystalline specimens

Abstract: Extending the methodology of X-ray crystallography to allow imaging of micrometre-sized non-crystalline specimens

Single-electron devices and their applications

Abstract: The goal of this paper is to review in brief the basic physics of single-election devices, as well as their-current and prospective applications. These devices based on the controllable transfer of single electrons between small conducting "islands", have already enabled several important scientific experiments. Several other applications of analog single-election devices in unique scientific instrumentation and metrology seem quite feasible. On the other hand, the prospect of silicon transistors being replaced by single-electron devices in integrated digital circuits faces tough challenges and remains uncertain. Nevertheless, even if this replacement does not happen, single electronics will continue to play an important role by shedding light on the fundamental size limitations of new electronic devices. Moreover, recent research in this field has generated some by-product ideas which may revolutionize random-access-memory and digital-data-storage technologies.

Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials.

Abstract: ContextLowering low-density lipoprotein cholesterol (LDL-C) is known to reduce risk of recurrent coronary heart disease in middle-aged men. However, this effect has been uncertain in elderly people and women.ObjectiveTo estimate the risk reduction of coronary heart disease and total mortality associated with statin drug treatment, particularly in elderly individuals and women.Data SourcesTrials published in English-language journals were retrieved by searching MEDLINE (1966–December 1998), bibliographies, and authors' reference files.Study SelectionStudies in which participants were randomized to statin or control treatment for at least 4 years and clinical disease or death was the primary outcome were included in the meta-analysis (5 of 182 initially identified).Data ExtractionInformation on sample size, study drug duration, type and dosage of statin drug, participant characteristics at baseline, reduction in lipids during intervention, and outcomes was abstracted independently by 2 authors (J.H. and S.V.) using a standardized protocol. Disagreements were resolved by consensus.Data SynthesisData from the 5 trials, with 30,817 participants, were included in this meta-analysis. The mean duration of treatment was 5.4 years. Statin drug treatment was associated with a 20% reduction in total cholesterol, 28% reduction in LDL-C, 13% reduction in triglycerides, and 5% increase in high-density lipoprotein cholesterol. Overall, statin drug treatment reduced risk 31% in major coronary events (95% confidence interval [CI], 26%-36%) and 21% in all-cause mortality (95% CI, 14%-28%). The risk reduction in major coronary events was similar between women (29%; 95% CI, 13%-42%) and men (31%; 95% CI, 26%-35%), and between persons aged at least 65 years (32%; 95% CI, 23%-39%) and persons younger than 65 years (31%; 95% CI, 24%-36%).ConclusionsOur meta-analysis indicates that reduction in LDL-C associated with statin drug treatment decreases the risk of coronary heart disease and all-cause mortality. The risk reduction was similar for men and women and for elderly and middle-aged persons.

Phenomenological model of anisotropic peak broadening in powder diffraction

Abstract: Anisotropic line-shape broadening (peak width which is not a smooth function of d-spacing) is frequently observed in powder diffraction patterns, and can be a source of considerable difficulty for whole-pattern fitting or Rietveld analysis. A model of the multi-dimensional distribution of lattice metrics within a powder sample is developed, leading naturally to a few parameters which can be varied to achieve optimal line-shape fits. Conditions on these parameters are derived for all crystal systems, and the method is illustrated with two examples: sodium p-hydroxybenzoate and rubidium fulleride.

Chiari I malformation redefined: clinical and radiographic findings for 364 symptomatic patients.

Abstract: PATIENTS AND METHODS Patients Baseline assessments Morphological features of the PCF Volume of the PCF Pedigree development and assessment of familial aggregation Statistical analyses

Statistical issues in ecological meta‐analyses

Abstract: Meta-analysis is the use of statistical methods to summarize research findings across studies. Special statistical methods are usually needed for meta-analysis, both because effect-size indexes are typically highly heteroscedastic and because it is desirable to be able to distinguish between-study variance from within-study sampling-error variance. We outline a number of considerations related to choosing methods for the meta-analysis of ecological data, including the choice of parametric vs. resampling methods, reasons for conducting weighted analyses where possible, and comparisons fixed vs. mixed models in categorical and regression-type analyses.

A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation.

Abstract: The TGF-beta superfamily of proteins regulates many different biological processes, including cell growth, differentiation and embryonic pattern formation. TGF-beta-like factors signal across cell membranes through complexes of transmembrane receptors known as type I and type II serine/threonine-kinase receptors, which in turn activate the SMAD signalling pathway. On the inside of the cell membrane, a receptor-regulated class of SMADs are phosphorylated by the type-I-receptor kinase. In this way, receptors for different factors are able to pass on specific signals along the pathway: for example, receptors for bone morphogenetic protein (BMP) target SMADs 1, 5 and 8, whereas receptors for activin and TGF-beta target SMADs 2 and 3. Phosphorylation of receptor-regulated SMADs induces their association with Smad4, the 'common-partner' SMAD, and stimulates accumulation of this complex in the nucleus, where it regulates transcriptional responses. Here we describe Smurf1, a new member of the Hect family of E3 ubiquitin ligases. Smurf1 selectively interacts with receptor-regulated SMADs specific for the BMP pathway in order to trigger their ubiquitination and degradation, and hence their inactivation. In the amphibian Xenopus laevis, Smurf1 messenger RNA is localized to the animal pole of the egg; in Xenopus embryos, ectopic Smurf1 inhibits the transmission of BMP signals and thereby affects pattern formation. Smurf1 also enhances cellular responsiveness to the Smad2 (activin/TGF-beta) pathway. Thus, targeted ubiquitination of SMADs may serve to control both embryonic development and a wide variety of cellular responses to TGF-beta signals.

Shape Statistics: Procrustes Superimpositions and Tangent Spaces

Abstract: The shape of a set of labeled points corresponds to those attributes of the configuration that are invariant to the effects of translation, rotation, and scale. Procrustes distance may be used to compare different shapes and also serve as a metric that may be used to define multidimensional shape spaces. This paper demonstrates that the preshape space of planar triangles Procrustes aligned to a reference triangle corresponds to a unit hemisphere. An overview of methods used as linear approximations of D. G. Kendall's non-Euclidean shape space is given, and the equivalence of several methods based on orthogonal projections is shown. Some problems with approximations based on stereo graphic projections are also discussed. A simple example using artificial data is included.

Muscle and Movement Representations in the Primary Motor Cortex

Abstract: What aspects of movement are represented in the primary motor cortex (M1): relatively low-level parameters like muscle force, or more abstract parameters like handpath? To examine this issue, the activity of neurons in M1 was recorded in a monkey trained to perform a task that dissociates three major variables of wrist movement: muscle activity, direction of movement at the wrist joint, and direction of movement in space. A substantial group of neurons in M1 (28 out of 88) displayed changes in activity that were muscle-like. Unexpectedly, an even larger group of neurons in M1 (44 out of 88) displayed changes in activity that were related to the direction of wrist movement in space independent of the pattern of muscle activity that generated the movement. Thus, both "muscles" and "movements" appear to be strongly represented in M1.

Event-by-Event Fluctuations in Heavy Ion Collisions and the QCD Critical Point

Abstract: The event-by-event fluctuations of suitably chosen observables in heavy ion collisions at CERN SPS, BNL RHIC, and CERN LHC can tell us about the thermodynamic properties of the hadronic system at freeze-out. By studying these fluctuations as a function of varying control parameters, it is possible to learn much about the phase diagram of QCD. As a timely example, we stress the methods by which present experiments at the CERN SPS can locate the second-order critical end point of the first-order transition between quark-gluon plasma and hadron matter. Those event-by-event signatures which are characteristic of freeze-out in the vicinity of the critical point will exhibit nonmonotonic dependence on control parameters. We focus on observables constructed from the multiplicity and transverse momenta of charged pions. We first consider how the event-by-event fluctuations of such observables are affected by Bose-Einstein correlations, by resonances which decay after freeze-out, and by fluctuations in the transverse flow velocity. We compare our thermodynamic predictions for such noncritical event-by-event fluctuations with NA49 data, finding broad agreement. We then focus on effects due to thermal contact between the observed pions and a heat bath with a given (possibly singular) specific heat, due to the direct coupling between themore » critical fluctuations of the sigma field and the observed pions. We also discuss the effect of the pions produced in the decay of sigma particles just above threshold after freeze-out on the inclusive pion spectrum and on multiplicity fluctuations. We estimate the size of these nonmonotonic effects, which appear near the critical point, including restrictions imposed by finite size and finite time, and conclude that they should be easily observable. (c) 1999 The American Physical Society.« less

Body Composition, Visceral Fat, Leptin, and Insulin Resistance in Asian Indian Men

Abstract: There is a high prevalence of type 2 diabetes mellitus and coronary artery disease among urban and migrant Asian Indians despite the absence of traditional risk factors. Evidence exists that Asian Indians are more hyperinsulinemic than Caucasians and that hyperinsulinemia may be important in the development of these diseases. To test whether insulin action was related to total or regional adiposity and to explore the potential role of plasma leptin and lipids, we measured insulin-mediated glucose disposal by the euglycemic insulin clamp, adipose distribution and muscle volume using computed axial tomography, and fasting serum leptin and lipid levels in 20 healthy Asian Indian male volunteers (age, 36 ± 10 yr). A mean body mass index of 24.5 ± 2.5 kg/m2 was associated with an unusually high percentage of body fat (33 ± 7%). The majority of the fat was sc, and 16% was visceral (intraabdominal) adipose tissue. The majority (66%) of these nonobese men were insulin resistant. The mean fasting serum leptin leve...

Liver Pathology and the Metabolic Syndrome X in Severe Obesity

Abstract: The metabolic syndrome X, characterized by insulin resistance, dyslipidemia, hypertension, and a male, visceral distribution of adipose tissue, is associated with increased morbidity and mortality from several prevalent diseases, such as diabetes, cancers, myocardial infarction, and stroke. Because the liver has a central role in carbohydrate, lipid, and steroid metabolism, we investigated the relationships between liver pathology and the metabolic syndrome. Blood chemistry, anthropometry (waist/hip circumference ratio), and intraoperative routine knife biopsies of the liver were obtained in 551 (112 men) severely obese patients (body mass index, 47 +/- 9; mean +/- SD) undergoing antiobesity surgery. Steatosis was found in 86%, fibrosis in 74%, mild inflammation or steatohepatitis in 24%, and unexpected cirrhosis in 2% (n = 11) of the patients. The risk of steatosis was 2.6 times greater in men than in women (P < 0.0001). With each addition of 1 of the 4 components of the metabolic syndrome, elevated waist/hip ratio, impaired glucose tolerance, hypertension, and dyslipidemia, the risk of steatosis increased exponentially from 1- to 99-fold (P < 0.001). Fibrosis correlated with steatosis (r = 0.56; P < 0.0001), whereas patients with diabetes or impaired glucose tolerance had a 7-fold increased risk of fibrosis (P < 0.0001). Diabetes, steatosis, and age were all significant indicators of cirrhosis, whereas inflammation was only associated with age. We conclude that the metabolic syndrome via impaired glucose tolerance is strongly correlated with steatosis, fibrosis, and cirrhosis of the liver.

The role of trace metals in photosynthetic electron transport in O2-evolving organisms

Abstract: Iron is the quantitatively most important trace metal involved in thylakoid reactions of all oxygenic organisms since linear (= non-cyclic) electron flow from H2O to NADP+ involves PS II (2–3 Fe), cytochrome b6-f (5 Fe), PS I (12 Fe), and ferredoxin (2 Fe); (replaceable by metal-free flavodoxin in certain cyanobacteria and algae under iron deficiency). Cytochrome c6 (1 Fe) is the only redox catalyst linking the cytochrome b6-f complex to PS I in most algae; in many cyanobacteria and Chlorophyta cytochrome c6 and the copper-containing plastocyanin are alternatives, with the availability of iron and copper regulating their relative expression, while higher plants only have plastocyanin. Iron, copper and zinc occur in enzymes that remove active oxygen species and that are in part bound to the thylakoid membrane. These enzymes are ascorbate peroxidase (Fe) and iron-(cyanobacteria, and most al gae) and copper-zinc- (some algae; higher plants) superoxide dismutase. Iron-containing NAD(P)H-PQ oxidoreductase in thylakoids of cyanobacteria and many eukaryotes may be involved in cyclic electron transport around PS I and in chlororespiration. Manganese is second to iron in its quantitative role in the thylakoids, with four Mn (and 1 Ca) per PS II involved in O2 evolution. The roles of the transition metals in redox catalysts can in broad terms be related to their redox chemistry and to their availability to organisms at the time when the pathways evolved. The quantitative roles of these trace metals varies genotypically (e.g. the greater need for iron in thylakoid reactions of cyanobacteria and rhodophytes than in other O2-evolvers as a result of their lower PS II:PS I ratio) and phenotypically (e.g. as a result of variations in PS II:PS I ratio with the spectral quality of incident radiation).

Flower Constancy, Insect Psychology, and Plant Evolution

Abstract: Individuals of some species of pollinating insects tend to restrict their visits to only a few of the available plant species, in the process bypassing valuable food sources. The question of why this flower constancy exists is a rich and important one with implications for the organization of natural communities of plants, floral evolution, and our understanding of the learning processes involved in finding food. Some scientists have assumed that flower constancy is adaptive per se. Others argued that constancy occurs because memory capacity for floral features in insects is limited, but attempts to identify the limitations often remained rather simplistic. We elucidate now different sensory and motor memories from natural foraging tasks are stored and retrieved, using concepts from modern learning science and visual search, and conclude that flower constancy is likely to have multiple causes. Possible constraints favoring constancy are interference sensitivity of short-term memory, and temporal limitations on retrieving information from long-term memory as rapidly as from short-term memory, but further empirical evidence is needed to substantiate these possibilities. In addition, retrieving memories may be slower and more prone to errors when there are several options than when an insect copes with only a single task. In addition to memory limitations, we also point out alternative explanations for flower constancy. We then consider the way in which floral parameters, such as interplant distances, nectar rewards, flower morphology, and floral color (as seen through bees' eyes) affect constancy. Finally, we discuss the implications of pollinator constancy for plant evolution. To date there is no evidence that flowers have diverged to favor constancy, although the appropriate tests may not have yet been conducted. However, there is good evidence against the notion that pollinator constancy is involved in speciation or maintenance of plant species integrity.

Role of Oral Bacteria in Respiratory Infection

Abstract: An association between oral conditions such as periodontal disease and several respiratory conditions has been noted. For example, recent evidence has suggested a central role for the oral cavity in the process of respiratory infection. Oral periodontopathic bacteria can be aspirated into the lung to cause aspiration pneumonia. The teeth may also serve as a reservoir for respiratory pathogen colonization and subsequent nosocomial pneumonia. Typical respiratory pathogens have been shown to colonize the dental plaque of hospitalized intensive care and nursing home patients. Once established in the mouth, these pathogens may be aspirated into the lung to cause infection. Other epidemiologic studies have noted a relationship between poor oral hygiene or periodontal bone loss and chronic obstructive pulmonary disease. Several mechanisms are proposed to explain the potential role of oral bacteria in the pathogenesis of respiratory infection: 1. aspiration of oral pathogens (such as Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, etc.) into the lung to cause infection; 2. periodontal disease-associated enzymes in saliva may modify mucosal surfaces to promote adhesion and colonization by respiratory pathogens, which are then aspirated into the lung; 3. periodontal disease-associated enzymes may destroy salivary pellicles on pathogenic bacteria to hinder their clearance from the mucosal surface; and 4. cytokines originating from periodontal tissues may alter respiratory epithelium to promote infection by respiratory pathogens.

Natural course of adolescent major depressive disorder: I. Continuity into young adulthood.

Abstract: Objective To examine the course of adolescent major depressive disorder (MDD) by comparing rates of mood and non-mood disorders between age 19 and 24 years in participants with a history of adolescent MDD versus participants with adolescent adjustment disorder with depressed mood, nonaffective disorder, and no disorder. Method Participants from a large community sample who had been interviewed twice during adolescence completed a third interview assessing Axis I psychopathology and antisocial and borderline personality disorders after their 24th birthday: 261 participants with MDD, 73 with adjustment disorder, 133 with nonaffective disorder, and 272 with no disorder through age 18. Results MDD in young adulthood was significantly more common in the adolescent MDD group than the nonaffective and no disorder groups (average annual rate of MDD=9.0%, 5.6%, and 3.7%, respectively). Adolescents with MDD also had a high rate of nonaffective disorders in young adulthood (annual nonaffective disorder rate=6.6%) but did not differ from adolescents with nonaffective disorder (7.2%). Prevalence rates of dysthymia and bipolar disorder were low (1%). Adolescents with adjustment disorder exhibited similar rates of MDD and nonaffective disorders in young adulthood as adolescents with MDD. Conclusions This study documents the significant continuity of MDD from adolescence to young adulthood. Public health implications of the findings are discussed. J. Am. Acad. Child Adolesc. Psychiatry, 1999, 38(1):56–63.

Chiral symmetry restoration and dileptons in relativistic heavy ion collisions

Abstract: The current theoretical status in the analysis and interpretation of low-mass dilepton measurements in (ultra-) relativistic heavy-ion experiments is reviewed. Special emphasis is put on potential signals of (partial) restoration of dynamically broken chiral symmetry in a hot and dense hadronic medium. It follows from chiral symmetry alone that parity partners of hadronic correlation functions must become identical when the symmetry is restored. The assessment of medium effects in the vector channel, which governs the dilepton production, thus necessitates a simultaneous treatment of the vector and axialvector degrees of freedom. While significant progress in this respect has been made some open questions remain in establishing a rigorous link in the mass region below 1 GeV. From the present calculations a suggestive 'quark-hadron duality' emerges near the phase boundary. It implies substantial medium effects in the dilepton signal from the hadronic phase which smoothly matches a perturbative description within the plasma phase.

Exogenous administration of heme oxygenase-1 by gene transfer provides protection against hyperoxia-induced lung injury

Abstract: Heme oxygenase-1 (HO-1) confers protection against a variety of oxidant-induced cell and tissue injury. In this study, we examined whether exogenous administration of HO-1 by gene transfer could also confer protection. We first demonstrated the feasibility of overexpressing HO-1 in the lung by gene transfer. A fragment of the rat HO-1 cDNA clone containing the entire coding region was cloned into plasmid pAC-CMVpLpA, and recombinant adenoviruses containing the rat HO-1 cDNA fragment Ad5-HO-1 were generated by homologous recombination. Intratracheal administration of Ad5-HO-1 resulted in a time-dependent increase in expression of HO-1 mRNA and protein in the rat lungs. Increased HO-1 protein expression was detected diffusely in the bronchiolar epithelium of rats receiving Ad5-HO-1, as assessed by immunohistochemical studies. We then examined whether ectopic expression of HO-1 could confer protection against hyperoxia-induced lung injury. Rats receiving Ad5-HO-1, but not AdV-betaGal, a recombinant adenovirus expressing Escherichia coli beta-galactosidase, before exposure to hyperoxia (>99% O2) exhibited marked reduction in lung injury, as assessed by volume of pleural effusion and histological analyses (significant reduction of edema, hemorrhage, and inflammation). In addition, rats receiving Ad5-HO-1 also exhibited increased survivability against hyperoxic stress when compared with rats receiving AdV-betaGal. Expression of the antioxidant enzymes manganese superoxide dismutase (Mn-SOD) and copper-zinc superoxide dismutase (CuZn-SOD) and of L-ferritin and H-ferritin was not affected by Ad5-HO-1 administration. Furthermore, rats treated with Ad5-HO-1 exhibited attenuation of hyperoxia-induced neutrophil inflammation and apoptosis. Taken together, these data suggest the feasibility of high-level HO-1 expression in the rat lung by gene delivery. To our knowledge, we have demonstrated for the first time that HO-1 can provide protection against hyperoxia-induced lung injury in vivo by modulation of neutrophil inflammation and lung apoptosis.

Paxillin LD4 Motif Binds PAK and PIX through a Novel 95-kD Ankyrin Repeat, ARF–GAP Protein: A Role in Cytoskeletal Remodeling

Abstract: Paxillin is a focal adhesion adaptor protein involved in the integration of growth factor- and adhesion-mediated signal transduction pathways. Repeats of a leucine-rich sequence named paxillin LD motifs (Brown M.C., M.S. Curtis, and C.E. Turner. 1998. Nature Struct. Biol. 5:677–678) have been implicated in paxillin binding to focal adhesion kinase (FAK) and vinculin. Here we demonstrate that the individual paxillin LD motifs function as discrete and selective protein binding interfaces. A novel scaffolding function is described for paxillin LD4 in the binding of a complex of proteins containing active p21 GTPase–activated kinase (PAK), Nck, and the guanine nucleotide exchange factor, PIX. The association of this complex with paxillin is mediated by a new 95-kD protein, p95PKL (paxillin-kinase linker), which binds directly to paxillin LD4 and PIX. This protein complex also binds to Hic-5, suggesting a conservation of LD function across the paxillin superfamily. Cloning of p95PKL revealed a multidomain protein containing an NH2-terminal ARF–GAP domain, three ankyrin-like repeats, a potential calcium-binding EF hand, calmodulin-binding IQ motifs, a myosin homology domain, and two paxillin-binding subdomains (PBS). Green fluorescent protein- (GFP-) tagged p95PKL localized to focal adhesions/complexes in CHO.K1 cells. Overexpression in neuroblastoma cells of a paxillin LD4 deletion mutant inhibited lamellipodia formation in response to insulin-like growth fac- tor-1. Microinjection of GST–LD4 into NIH3T3 cells significantly decreased cell migration into a wound. These data implicate paxillin as a mediator of p21 GTPase–regulated actin cytoskeletal reorganization through the recruitment to nascent focal adhesion structures of an active PAK/PIX complex potentially via interactions with p95PKL.

CoREST: A functional corepressor required for regulation of neural-specific gene expression

Abstract: Several genes encoding proteins critical to the neuronal phenotype, such as the brain type II sodium channel gene, are expressed to high levels only in neurons. This cell specificity is due, in part, to long-term repression in nonneural cells mediated by the repressor protein REST/NRSF (RE1 silencing transcription factor/neural-restrictive silencing factor). We show here that CoREST, a newly identified human protein, functions as a corepressor for REST. A single zinc finger motif in REST is required for CoREST interaction. Mutations of the motif that disrupt binding also abrogate repression. When fused to a Gal4 DNA-binding domain, CoREST functions as a repressor. CoREST is present in cell lines that express REST, and the proteins are found in the same immunocomplex. CoREST contains two SANT (SW13/ADA2/NCoR/TFIIIB B) domains, a structural feature of the nuclear receptor and silencing mediator for retinoid and thyroid human receptors (SMRT)-extended corepressors that mediate inducible repression by steroid hormone receptors. Together, REST and CoREST mediate repression of the type II sodium channel promoter in nonneural cells, and the REST/CoREST complex may mediate long-term repression essential to maintenance of cell identity.

Physiological regulation of G protein-linked signaling.

Abstract: Heterotrimeric G proteins in vertebrates constitute a family molecular switches that transduce the activation of a populous group of cell-surface receptors to a group of diverse effector units. The...

Empirical approaches to quantifying interaction intensity: competition and facilitation along productivity gradients

Abstract: Quantitative synthesis across studies requires consistent measures of effect size among studies. In community ecology, these measures of effect size will often be some measure of the strength of interactions between taxa. However, indices of interaction strength vary greatly among both theoretical and empirical studies, and the connection between hypotheses about interaction strength and the metrics that are used to test these hypotheses are often not explicit. We describe criteria for choosing appropriate metrics and methods for comparing them among studies at three stages of designing a meta-analysis to test hypotheses about variation in interaction intensity: (1) the choice of response variable; (2) how effect size is calculated using the response in two treatments; and (3) whether there is a consistent quantitative effect across all taxa and systems studied or only qualitatively similar effects within each taxon–system combination. The consequences of different choices at each of these stages are illu...

Composite co-activator ARC mediates chromatin-directed transcriptional activation

Abstract: Gene activation in eukaryotes is regulated by complex mechanisms in which the recruitment and assembly of the transcriptional machinery is directed by gene- and cell-type-specific DNA-binding proteins. When DNA is packaged into chromatin, the regulation of gene activation requires new classes of chromatin-targeting activity. In humans, a multisubunit cofactor functions in a chromatin-selective manner to potentiate synergistic gene activation by the transcriptional activators SREBP-1a and Sp1. Here we show that this activator-recruited cofactor (ARC) interacts directly with several different activators, including SREBP-1a, VP16 and the p65 subunit of NF-kappaB, and strongly enhances transcription directed by these activators in vitro with chromatin-assembled DNA templates. The ARC complex consists of 16 or more subunits; some of these are novel gene products, whereas others are present in other multisubunit cofactors, such as CRSP, NAT and mammalian Mediator. Detailed analysis indicates that the ARC complex is probably identical to the nuclear hormone-receptor cofactor DRIP. Thus, ARC/DRIP is a large composite co-activator that belongs to a family of related cofactors and is targeted by different classes of activator to mediate transcriptional stimulation.

Physical Parameters of GRB 970508 and GRB 971214 from Their Afterglow Synchrotron Emission

Abstract: We have calculated synchrotron spectra of relativistic blast waves and find predicted characteristic frequencies that are more than an order of magnitude different from previous calculations. For the case of an adiabatically expanding blast wave, which is applicable to observed gamma-ray burst (GRB) afterglows at late times, we give expressions to infer the physical properties of the afterglow from the measured spectral features. We show that enough data exist for GRB 970508 to compute unambiguously the ambient density, n = 0.03 cm-3, and the blast wave energy per unit solid angle, = 3 × 1052 ergs/4π sr. We also compute the energy density in electrons and magnetic field. We find that they are 12% and 9%, respectively, of the nucleon energy density and thus confirm for the first time that both are close to but below equipartition. For GRB 971214, we discuss the break found in its spectrum by Ramaprakash et al. It can be interpreted either as the peak frequency or as the cooling frequency; both interpretations have some problems, but on balance the break is more likely to be the cooling frequency. Even when we assume this, our ignorance of the self-absorption frequency and presence or absence of beaming make it impossible to constrain the physical parameters of GRB 971214 very well.