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Showing papers by "University of Arizona published in 2000"


Journal ArticleDOI
TL;DR: The recent proliferation of research on collective action frames and framing processes in relation to social movements indicates that framing processes have come to be regarded, alongside resource mobilization and political opportunity processes, as a central dynamic in understanding the character and course of social movements.
Abstract: ■ Abstract The recent proliferation of scholarship on collective action frames and framing processes in relation to social movements indicates that framing processes have come to be regarded, alongside resource mobilization and political opportunity processes, as a central dynamic in understanding the character and course of social movements. This review examines the analytic utility of the framing literature for un- derstanding social movement dynamics. We first review how collective action frames have been conceptualized, including their characteristic and variable features. We then examine the literature related to framing dynamics and processes. Next we review the literature regarding various contextual factors that constrain and facilitate framing processes. We conclude with an elaboration of the consequences of framing processes for other movement processes and outcomes. We seek throughout to provide clarifi- cation of the linkages between framing concepts/processes and other conceptual and theoretical formulations relevant to social movements, such as schemas and ideology.

7,717 citations


Journal ArticleDOI
24 Mar 2000-Science
TL;DR: The nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome is determined using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map.
Abstract: The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

6,180 citations


Journal ArticleDOI
01 Jun 2000
TL;DR: Evidence for plant stress signaling systems is summarized, some of which have components analogous to those that regulate osmotic stress responses of yeast, some that presumably function in intercellular coordination or regulation of effector genes in a cell-/tissue-specific context required for tolerance of plants.
Abstract: ▪ Abstract Plant responses to salinity stress are reviewed with emphasis on molecular mechanisms of signal transduction and on the physiological consequences of altered gene expression that affect biochemical reactions downstream of stress sensing. We make extensive use of comparisons with model organisms, halophytic plants, and yeast, which provide a paradigm for many responses to salinity exhibited by stress-sensitive plants. Among biochemical responses, we emphasize osmolyte biosynthesis and function, water flux control, and membrane transport of ions for maintenance and re-establishment of homeostasis. The advances in understanding the effectiveness of stress responses, and distinctions between pathology and adaptive advantage, are increasingly based on transgenic plant and mutant analyses, in particular the analysis of Arabidopsis mutants defective in elements of stress signal transduction pathways. We summarize evidence for plant stress signaling systems, some of which have components analogous to t...

4,596 citations


Journal ArticleDOI
18 May 2000-Nature
TL;DR: Unlike eukaryotes, which evolve principally through the modification of existing genetic information, bacteria have obtained a significant proportion of their genetic diversity through the acquisition of sequences from distantly related organisms.
Abstract: Unlike eukaryotes, which evolve principally through the modification of existing genetic information, bacteria have obtained a significant proportion of their genetic diversity through the acquisition of sequences from distantly related organisms. Horizontal gene transfer produces extremely dynamic genomes in which substantial amounts of DNA are introduced into and deleted from the chromosome. These lateral transfers have effectively changed the ecological and pathogenic character of bacterial species.

3,640 citations


Journal ArticleDOI
TL;DR: In this article, the final results of the Hubble Space Telescope Key Project to measure the Hubble constant are presented, and the implications of these results for cosmology are discussed and compared with other, global methods for measuring the Hubble constants.
Abstract: We present here the final results of the Hubble Space Telescope Key Project to measure the Hubble constant. We summarize our method, the results and the uncertainties, tabulate our revised distances, and give the implications of these results for cosmology. The analysis presented here benefits from a number of recent improvements and refinements, including (1) a larger LMC Cepheid sample to define the fiducial period-luminosity (PL) relations, (2) a more recent HST Wide Field and Planetary Camera 2 (WFPC2) photometric calibration, (3) a correction for Cepheid metallicity, and (4) a correction for incompleteness bias in the observed Cepheid PL samples. New, revised distances are given for the 18 spiral galaxies for which Cepheids have been discovered as part of the Key Project, as well as for 13 additional galaxies with published Cepheid data. The new calibration results in a Cepheid distance to NGC 4258 in better agreement with the maser distance to this galaxy. Based on these revised Cepheid distances, we find values (in km/sec/Mpc) of H0 = 71 +/- 2 (random) +/- 6 (systematic) (type Ia supernovae), 71 +/- 2 +/- 7 (Tully-Fisher relation), 70 +/- 5 +/- 6 (surface brightness fluctuations), 72 +/- 9 +/- 7 (type II supernovae), and 82 +/- 6 +/- 9 (fundamental plane). We combine these results for the different methods with 3 different weighting schemes, and find good agreement and consistency with H0 = 72 +/- 8. Finally, we compare these results with other, global methods for measuring the Hubble constant.

2,528 citations


Journal ArticleDOI
TL;DR: The outlines of a model that integrates autonomic, attentional, and affective systems into a functional and structural network that may help to guide us in the understanding of emotion regulation and dysregulation are presented.

2,217 citations


Journal ArticleDOI
03 Aug 2000-Nature
TL;DR: Many genes underlying the classification of this subset of melanomas are differentially regulated in invasive melanomas that form primitive tubular networks in vitro, a feature of some highly aggressive metastatic melanomas.
Abstract: The most common human cancers are malignant neoplasms of the skin. Incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease. Despite significant effort to identify independent predictors of melanoma outcome, no accepted histopathological, molecular or immunohistochemical marker defines subsets of this neoplasm. Accordingly, though melanoma is thought to present with different 'taxonomic' forms, these are considered part of a continuous spectrum rather than discrete entities. Here we report the discovery of a subset of melanomas identified by mathematical analysis of gene expression in a series of samples. Remarkably, many genes underlying the classification of this subset are differentially regulated in invasive melanomas that form primitive tubular networks in vitro, a feature of some highly aggressive metastatic melanomas. Global transcript analysis can identify unrecognized subtypes of cutaneous melanoma and predict experimentally verifiable phenotypic characteristics that may be of importance to disease progression.

2,058 citations


Journal ArticleDOI
TL;DR: This paper investigated whether procedural and interactional justice affect work-related outcomes through different social exchange relationships, and found that interactional fairness affects work related outcomes through a variety of social exchange relations.
Abstract: This research investigated whether procedural and interactional justice affect work-related outcomes through different social exchange relationships. The findings extend previous research by demons...

2,007 citations


Journal ArticleDOI
TL;DR: The molecular laboratory model of spore resistance mechanisms is summarized and attempts to use the model as a basis for exploration of the resistance of spores to environmental extremes both on Earth and during postulated interplanetary transfer through space as a result of natural impact processes.
Abstract: Endospores of Bacillus spp., especially Bacillus subtilis, have served as experimental models for exploring the molecular mechanisms underlying the incredible longevity of spores and their resistance to environmental insults. In this review we summarize the molecular laboratory model of spore resistance mechanisms and attempt to use the model as a basis for exploration of the resistance of spores to environmental extremes both on Earth and during postulated interplanetary transfer through space as a result of natural impact processes.

1,852 citations


Journal ArticleDOI
TL;DR: The survey results support the value of in vivo toxicology studies to predict for many significant HTs associated with pharmaceuticals and have helped to identify HT categories that may benefit from improved methods.

1,699 citations


Journal ArticleDOI
TL;DR: In this article, the SOS1 (Salt Overly Sensitive 1) locus is cloned and predicted to encode a 127-kDa protein with 12 transmembrane domains in the N-terminal part and a long hydrophilic cytoplasmic tail.
Abstract: In Arabidopsis thaliana, the SOS1 (Salt Overly Sensitive 1) locus is essential for Na+ and K+ homeostasis, and sos1 mutations render plants more sensitive to growth inhibition by high Na+ and low K+ environments. SOS1 is cloned and predicted to encode a 127-kDa protein with 12 transmembrane domains in the N-terminal part and a long hydrophilic cytoplasmic tail in the C-terminal part. The transmembrane region of SOS1 has significant sequence similarities to plasma membrane Na+/H+ antiporters from bacteria and fungi. Sequence analysis of various sos1 mutant alleles reveals several residues and regions in the transmembrane as well as the tail parts that are critical for SOS1 function in plant salt tolerance. SOS1 gene expression in plants is up-regulated in response to NaCl stress. This up-regulation is abated in sos3 or sos2 mutant plants, suggesting that it is controlled by the SOS3/SOS2 regulatory pathway.

Journal ArticleDOI
TL;DR: Rapid defibrillation by nonmedical personnel using an automated external defibrillator can improve survival after out-of-hospital cardiac arrest due to ventricular fibrillation.
Abstract: Background The use of automated external defibrillators by persons other than paramedics and emergency medical technicians is advocated by the American Heart Association and other organizations. However, there are few data on the outcomes when the devices are used by nonmedical personnel for out-of-hospital cardiac arrest. Methods We studied a prospective series of cases of sudden cardiac arrest in casinos. Casino security officers were instructed in the use of automated external defibrillators. The locations where the defibrillators were stored in the casinos were chosen to make possible a target interval of three minutes or less from collapse to the first defibrillation. Our protocol called for a defibrillation first (if feasible), followed by manual cardiopulmonary resuscitation. The primary outcome was survival to discharge from the hospital. Results Automated external defibrillators were used in 105 patients whose initial cardiac rhythm was ventricular fibrillation. Fifty-six of the patients (53 perc...

Journal ArticleDOI
TL;DR: In this article, the authors examine how a retailer might better manage the hold-up potential of these transaction-specific investments (TSIs) through the use of three control mechanisms: supplier's TSIs, the development of relational norms, and the explicit contracts.
Abstract: Powerful suppliers often require retailers to make significant idiosyncratic investments to improve coordination between organizations and to enhance the supplier’s presence in the end market. The authors examine how a retailer might better manage the hold-up potential of these transaction-specific investments (TSIs) through the use of three control mechanisms: supplier’s TSIs, the development of relational norms, and the use of explicit contracts. Moreover, the authors consider the time-dependent nature of these mechanisms by observing their effects on commitment over the course of a relationship life cycle. The results indicate that (1) a retailer’s TSIs have a negative effect on its perceptions of supplier commitment; (2) a supplier’s TSIs and relational norms increase the retailer’s perception of supplier commitment, whereas explicit contracts are associated with perceptions of lower supplier commitment; and (3) each of the three control mechanisms moderates the negative impact of retailer in...

Journal ArticleDOI
TL;DR: The current state of knowledge regarding pathologic prognostic factors and predictive factors in colorectal carcinoma was evaluated and recommendations were made to increase the uniformity and completeness of pathologic evaluation of tumor specimens and to improve patient care.
Abstract: Background Under the auspices of the College of American Pathologists, the current state of knowledge regarding pathologic prognostic factors (factors linked to outcome) and predictive factors (factors predicting response to therapy) in colorectal carcinoma was evaluated. A multidisciplinary group of clinical (including the disciplines of medical oncology, surgical oncology, and radiation oncology), pathologic, and statistical experts in colorectal cancer reviewed all relevant medical literature and stratified the reported prognostic factors into categories that reflected the strength of the published evidence demonstrating their prognostic value. Accordingly, the following categories of prognostic factors were defined. Category I includes factors definitively proven to be of prognostic import based on evidence from multiple statistically robust published trials and generally used in patient management. Category IIA includes factors extensively studied biologically and/or clinically and repeatedly shown to have prognostic value for outcome and/or predictive value for therapy that is of sufficient import to be included in the pathology report but that remains to be validated in statistically robust studies. Category IIB includes factors shown to be promising in multiple studies but lacking sufficient data for inclusion in category I or IIA. Category III includes factors not yet sufficiently studied to determine their prognostic value. Category IV includes factors well studied and shown to have no prognostic significance. Materials and methods The medical literature was critically reviewed, and the analysis revealed specific points of variability in approach that prevented direct comparisons among published studies and compromised the quality of the collective data. Categories of variability recognized included the following: (1) methods of analysis, (2) interpretation of findings, (3) reporting of data, and (4) statistical evaluation. Additional points of variability within these categories were defined from the collective experience of the group. Reasons for the assignment of an individual prognostic factor to category I, II, III, or IV (categories defined by the level of scientific validation) were outlined with reference to the specific types of variability associated with the supportive data. For each factor and category of variability related to that factor, detailed recommendations for improvement were made. The recommendations were based on the following aims: (1) to increase the uniformity and completeness of pathologic evaluation of tumor specimens, (2) to enhance the quality of the data needed for definitive evaluation of the prognostic value of individual prognostic factors, and (3) ultimately, to improve patient care. Results and conclusions Factors that were determined to merit inclusion in category I were as follows: the local extent of tumor assessed pathologically (the pT category of the TNM staging system of the American Joint Committee on Cancer and the Union Internationale Contre le Cancer [AJCC/UICC]); regional lymph node metastasis (the pN category of the TNM staging system); blood or lymphatic vessel invasion; residual tumor following surgery with curative intent (the R classification of the AJCC/UICC staging system), especially as it relates to positive surgical margins; and preoperative elevation of carcinoembryonic antigen elevation (a factor established by laboratory medicine methods rather than anatomic pathology). Factors in category IIA included the following: tumor grade, radial margin status (for resection specimens with nonperitonealized surfaces), and residual tumor in the resection specimen following neoadjuvant therapy (the ypTNM category of the TNM staging system of the AJCC/UICC). (ABSTRACT TRUNCATED)

Journal ArticleDOI
TL;DR: Although about half of patients with chronic forms of major depression have a response to short-term treatment with either nefazodone or a cognitive behavioral-analysis system of psychotherapy, the combination of the two is significantly more efficacious than either treatment alone.
Abstract: Background Patients with chronic forms of major depression are difficult to treat, and the relative efficacy of medications and psychotherapy is uncertain. Methods We randomly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone (maximal dose, 600 mg per day), the cognitive behavioral-analysis system of psychotherapy (16 to 20 sessions), or both. At base line, all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression (indicating clinically significant depression). Remission was defined as a score of 8 or less at weeks 10 and 12. For patients who did not have remission, a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less. Raters were unaware of the patients' treatment assignments. Results Of the 681 patients, 662 attended at least one treatment session and were included in the analysis of response. The overall rate of response ...

Journal ArticleDOI
01 Sep 2000-Genetics
TL;DR: Comparison of rates of evolution for X-linked and autosomal pseudogenes suggests that the male mutation rate is 4 times the female mutation rate, but provides no evidence for a reduction in mutation rate that is specific to the X chromosome.
Abstract: Many previous estimates of the mutation rate in humans have relied on screens of visible mutants. We investigated the rate and pattern of mutations at the nucleotide level by comparing pseudogenes in humans and chimpanzees to (i) provide an estimate of the average mutation rate per nucleotide, (ii) assess heterogeneity of mutation rate at different sites and for different types of mutations, (iii) test the hypothesis that the X chromosome has a lower mutation rate than autosomes, and (iv) estimate the deleterious mutation rate. Eighteen processed pseudogenes were sequenced, including 12 on autosomes and 6 on the X chromosome. The average mutation rate was estimated to be approximately 2.5 x 10(-8) mutations per nucleotide site or 175 mutations per diploid genome per generation. Rates of mutation for both transitions and transversions at CpG dinucleotides are one order of magnitude higher than mutation rates at other sites. Single nucleotide substitutions are 10 times more frequent than length mutations. Comparison of rates of evolution for X-linked and autosomal pseudogenes suggests that the male mutation rate is 4 times the female mutation rate, but provides no evidence for a reduction in mutation rate that is specific to the X chromosome. Using conservative calculations of the proportion of the genome subject to purifying selection, we estimate that the genomic deleterious mutation rate (U) is at least 3. This high rate is difficult to reconcile with multiplicative fitness effects of individual mutations and suggests that synergistic epistasis among harmful mutations may be common.

Journal ArticleDOI
TL;DR: PERSIANN as discussed by the authors is an automated system for precipitation estimation from Remotely Sensed Information using Artificial Neural Networks, which is developed for the estimation of rainfall from geosynchronous satellite longwave infared imagery (GOES-IR) at a resolution of 0.25° × 0.75° every half-hour.
Abstract: PERSIANN, an automated system for Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks, has been developed for the estimation of rainfall from geosynchronous satellite longwave infared imagery (GOES–IR) at a resolution of 0.25° × 0.25° every half–hour. The accuracy of the rainfall product is improved by adaptively adjusting the network parameters using the instantaneous rain–rate estimates from the Tropical Rainfall Measurement Mission (TRMM) microwave imager (TMI product 2A12), and the random errors are further reduced by accumulation to a resolution of 1° × 1° daily. The authors' current GOES–IR–TRMM TMI based product, named PERSIANN–GT, was evaluated over the region 30°S–30°N, 90°E–30°W, which includes the tropical Pacific Ocean and parts of Asia, Australia, and the Americas. The resulting rain–rate estimates agree well with the National Climatic Data Center radar–gauge composite data over Florida and Texas (correlation coefficient r > 0.7). The product al...

Journal ArticleDOI
TL;DR: It is concluded that the subsequent development of asthma can be predicted with reasonable accuracy using simple, clinically based parameters.
Abstract: Because most cases of asthma begin during the first years of life, identification of young children at high risk of developing the disease is an important public health priority. We used data from the Tucson Children’s Respiratory Study to develop two indices for the prediction of asthma. A stringent index included frequent wheezing during the first 3 yr of life and either one major risk factor (parental history of asthma or eczema) or two of three minor risk factors (eosinophilia, wheezing without colds, and allergic rhinitis). A loose index required any wheezing during the first 3 yr of life plus the same combination of risk factors described previously. Children with a positive loose index were 2.6 to 5.5 times more likely to have active asthma between ages 6 and 13 than children with a negative loose index. Risk of having subsequent asthma increased to 4.3 to 9.8 times when a stringent index was used. We found that 59% of children with a positive loose index and 76% of those with a positive stringent index had active asthma in at least one survey during the school years. Over 95% of children with a negative stringent index never had active asthma between ages 6 and 13. We conclude that the subsequent development of asthma can be predicted with reasonable accuracy using simple, clinically based parameters. Recent longitudinal studies have suggested that, in a large proportion of all cases of asthma, asthmalike symptoms begin during the first years of life (1). Moreover, a long-term follow-up of children with different degrees of asthma severity enrolled in Melbourne, Australia, at the ages of 7 to 10 yr suggests that severity of asthma changes little with time (2). As a consequence, it is the children with the most severe asthma during the school years who become the most severe asthmatics during adult life and up to the age of 35. Children with mild infrequent asthma, on the other hand, have either mild symptoms in early adult life or their symptoms may remit indefinitely (2). Our own studies have also suggested that children who had wheezing lower respiratory tract illnesses during the first 3 yr of life and whose wheezing episodes persisted up to the age of 6 have significantly lower levels of lung function at age 6 compared with children whose wheezing symptoms started after the age of 3 (3). Taken as a whole, these data indicate that early initiation of asthma symptoms is associated with more significant functional deterioration and more persistence of symptoms into adult life (4‐6). The aforementioned considerations have suggested that identification of symptomatic infants and young children who will go on to develop asthma may be very important for the development of a strategy for early intervention aimed at changing the natural course of the disease (4). Unfortunately, wheezy infants who will go on to develop asthma coexist with a larger group of their peers who also wheeze in early life but whose symptoms are transient and usually subside during the preschool or early school years (7). Distinguishing these two asthmalike phenotypes during infancy and early childhood simply on the basis of their clinical presentation is problematic. There are still no reliable genetic markers available and the use of any single biochemical marker is still controversial (1). It is possible, however, that by use of both clinical data and simple, easily obtainable laboratory information, a combination of these parameters may be used to identify children at high risk of developing persistent symptoms in a clinical setting. In the present study, we used the longitudinal data available in the Tucson Children’s Respiratory Study to describe predictive indices for asthma during the school years among children having wheezing episodes during the first 3 yr of life.

Journal ArticleDOI
TL;DR: At 15 years, patients undergoing AVR had a better survival with a mechanical valve than with a bioprosthetic valve, largely because primary valve failure was virtually absent with mechanical valve.

Journal ArticleDOI
TL;DR: It is hypothesized that the continuous generation of variation in the rDNA may also play a role in how species interactions develop in ecosystems under different conditions of energy input and nutrient supply.
Abstract: Ecological stoichiometry is the study of the balance of multiple chemical elements in ecological interactions. This paper reviews recent findings in this area and seeks to broaden the stoichiometric concept for use in evolutionary studies, in integrating ecological dynamics with cellular and genetic mechanisms, and in developing a unified means for studying diverse organisms in diverse habitats. This broader approach would then be considered “biological stoichiometry”. Evidence supporting a hypothesised connection between the C:N:P stoichiometry of an organism and its growth rate (the “growth rate hypothesis”) is reviewed. Various data indicate that rapidly growing organisms commonly have low biomass C:P and N:P ratios. Evidence is then discussed suggesting that low C:P and N:P ratios in rapidly growing organisms reflect increased allocation to P-rich ribosomal RNA (rRNA), as rapid protein synthesis by ribosomes is required to support fast growth. Indeed, diverse organisms (bacteria, copepods, fishes, others) exhibit increased RNA levels when growing actively. This implies that evolutionary processes that generate, directly or indirectly, variation in a major life history trait (specific growth rate) have consequences for ecological dynamics due to their effects on organismal elemental composition. Genetic mechanisms by which organisms generate high RNA, high growth rate phenotypes are discussed next, focusing on the structure and organisation of the ribosomal RNA genes (the “rDNA”). In particular, published studies of a variety of taxa suggest an association between growth rate and variation in the length and content of the intergenic spacer (IGS) region of the rDNA tandem repeat unit. In particular, under conditions favouring increased growth or yield, the number of repeat units (“enhancers”) increases (and the IGS increases in length), and transcription rates of rRNA increase. In addition, there is evidence in the literature that increased numbers of copies of rDNA genes are associated with increased growth and production. Thus, a combination of genetic mechanisms may be responsible for establishing the growth potential, and thus the RNA allocation and C:N:P composition, of an organism. Furthermore, various processes, during both sexual and asexual reproduction, can generate variation in the rDNA to provide the raw material for selection and to generate ecologically significant variation in C:N:P stoichiometry. This leads us to hypothesize that the continuous generation of such variation may also play a role in how species interactions develop in ecosystems under different conditions of energy input and nutrient supply.


Journal ArticleDOI
TL;DR: In this article, the authors describe the heat transfer mechanisms operating as heat moves downward in the soil along steep temperature gradients during both wildfires and prescribed fires, and the relationship between the formation of fire-related watershed condition and subsequent surface runoff and erosion from wildland ecosystems is explored.

Journal ArticleDOI
TL;DR: A summary of the theoretical development and the empirical findings from the authors' research on the dimensions and impact of the hollow state in the domain of health and human services contracting can be found in this paper.
Abstract: For the past ten years the authors have conducted a concentrated research program on the dimensions and impact of the hollow state. The hollow state is a metaphor for the increasing use of third parties, often nonprofits, to deliver social services and generally act in the name of the state. The types of structures, incentives, and mechanisms used to control third-party providers have been the focus of this research. The empirical thrust of this research is on how effective various types of mechanisms, structures, and incentives are at promoting the effectiveness of contracted services. The normative question this research has raised, but not answered, is, What effect does government contracting with third-party providers have on the perceived legitimacy of the state? This article is a summary of the theoretical development and the empirical findings from the authors' research on the dimensions and impact of the hollow state in the domain of health and human services contracting. Elements of this article have appeared previously in this journal and in many others as well. The article's purpose is to integrate the authors' research on the hollow state. This is a summative article that seeks to bring together in one place what the authors have learned. In addition, new directions are explored for future research on the hollow state.

Journal ArticleDOI
TL;DR: Investigation of the role of the IEGArc in hippocampal plasticity shows that disruption of Arc protein expression impairs the maintenance phase of LTP without affecting its induction and impairs consolidation of LTM for spatial water task training without affecting task acquisition or short-term memory.
Abstract: It is widely believed that the brain processes information and stores memories by modifying and stabilizing synaptic connections between neurons. In experimental models of synaptic plasticity, such as long-term potentiation (LTP), the stabilization of changes in synaptic strength requires rapid de novo RNA and protein synthesis. Candidate genes, which could underlie activity-dependent plasticity, have been identified on the basis of their rapid induction in brain neurons. Immediate-early genes (IEGs) are induced in hippocampal neurons by high-frequency electrical stimulation that induces LTP and by behavioral training that results in long-term memory (LTM) formation. Here, we investigated the role of the IEGArc (also termed Arg3.1) in hippocampal plasticity. Arc protein is known to be enriched in dendrites of hippocampal neurons where it associates with cytoskeletal proteins (Lyford et al., 1995).Arc is also notable in that its mRNA and protein accumulate in dendrites at sites of recent synaptic activity (Steward et al., 1998). We used intrahippocampal infusions of antisense oligodeoxynucleotides to inhibit Arc protein expression and examined the effect of this treatment on both LTP and spatial learning. Our studies show that disruption of Arc protein expression impairs the maintenance phase of LTP without affecting its induction and impairs consolidation of LTM for spatial water task training without affecting task acquisition or short-term memory. Thus, Arc appears to play a fundamental role in the stabilization of activity-dependent hippocampal plasticity.

Journal ArticleDOI
TL;DR: The authors found little evidence for interaction with other breast cancer risk factors, and data indicate that height is an independent risk factor for postmenopausal breast cancer; in premenopausal women, this relation is less clear.
Abstract: The association between anthropometric indices and the risk of breast cancer was analyzed using pooled data from seven prospective cohort studies. Together, these cohorts comprise 337,819 women and 4,385 incident invasive breast cancer cases. In multivariate analyses controlling for reproductive, dietary, and other risk factors, the pooled relative risk (RR) of breast cancer per height increment of 5 cm was 1.02 (95% confidence interval (Cl): 0.96, 1.10) in premenopausal women and 1.07 (95% Cl: 1.03, 1.12) in postmenopausal women. Body mass index (BMI) showed significant inverse and positive associations with breast cancer among pre- and postmenopausal women, respectively; these associations were nonlinear. Compared with premenopausal women with a BMI of less than 21 kg/m2, women with a BMI exceeding 31 kg/m2 had an RR of 0.54 (95% Cl: 0.34, 0.85). In postmenopausal women, the RRs did not increase further when BMI exceeded 28 kg/m2; the RR for these women was 1.26 (95% Cl: 1.09, 1.46). The authors found little evidence for interaction with other breast cancer risk factors. Their data indicate that height is an independent risk factor for postmenopausal breast cancer; in premenopausal women, this relation is less clear. The association between BMI and breast cancer varies by menopausal status. Weight control may reduce the risk among postmenopausal women.

Journal ArticleDOI
TL;DR: In this paper, surface-induced dissociation, along with gas-phase collision-induced disociation performed under a variety of conditions, has been used to refine the general'mobile proton' model and to determine how and why enhanced cleavages occur at aspartic acid residues and protonated histidine residues.
Abstract: Protein identification and peptide sequencing by tandem mass spectrometry requires knowledge of how peptides fragment in the gas phase, specifically which bonds are broken and where the charge(s) resides in the products. For many peptides, cleavage at the amide bonds dominate, producing a series of ions that are designated b and y. For other peptides, enhanced cleavage occurs at just one or two amino acid residues. Surface-induced dissociation, along with gas-phase collision-induced dissociation performed under a variety of conditions, has been used to refine the general 'mobile proton' model and to determine how and why enhanced cleavages occur at aspartic acid residues and protonated histidine residues. Enhanced cleavage at acidic residues occurs when the charge is unavailable to the peptide backbone or the acidic side-chain. The acidic H of the side-chain then serves to initiate cleavage at the amide bond immediately C-terminal to Asp (or Glu), producing an anhydride. In contrast, enhanced cleavage occurs at His when the His side-chain is protonated, turning His into a weak acid that can initiate backbone cleavage by transferring a proton to the backbone. This allows the nucleophilic nitrogen of the His side-chain to attack and form a cyclic structure that is different from the 'typical' backbone cleavage structures.

Journal ArticleDOI
TL;DR: Exposure of young children to older children at home or to other children at day care protects against the development of asthma and frequent wheezing later in childhood.
Abstract: Background Young children with older siblings and those who attend day care are at increased risk for infections, which in turn may protect against the development of allergic diseases, including asthma. However, the results of studies examining the relation between exposure to other children and the subsequent development of asthma have been conflicting. Methods In a study involving 1035 children followed since birth as part of the Tucson Children's Respiratory Study, we determined the incidence of asthma (defined as at least one episode of asthma diagnosed by a physician when the child was 6 to 13 years old) and the prevalence of frequent wheezing (more than three wheezing episodes during the preceding year) in relation to the number of siblings at home and in relation to attendance at day care during infancy. Results The presence of one or more older siblings at home protected against the development of asthma (adjusted relative risk for each additional older sibling, 0.8; 95 percent confidence interva...

Journal ArticleDOI
TL;DR: Using positron emission tomography, it is found contralateral activity correlated with graded cooling stimuli only in the dorsal margin of the middle/posterior insula in humans, which supports the proposal that central pain results from loss of the normal inhibition of pain by cold.
Abstract: Temperature sensation is regarded as a submodality of touch, but evidence suggests involvement of insular cortex rather than parietal somatosensory cortices. Using positron emission tomography (PET), we found contralateral activity correlated with graded cooling stimuli only in the dorsal margin of the middle/posterior insula in humans. This corresponds to the thermoreceptive- and nociceptive-specific lamina I spinothalamocortical pathway in monkeys, and can be considered an enteroceptive area within limbic sensory cortex. Because lesions at this site can produce the post-stroke central pain syndrome, this finding supports the proposal that central pain results from loss of the normal inhibition of pain by cold. Notably, perceived thermal intensity was well correlated with activation in the right (ipsilateral) anterior insular and orbitofrontal cortices.

Journal ArticleDOI
TL;DR: A 12-person panel of physicians with expertise in ophthalmologic, pediatric, and rheumatologic disease, in research, and in the use of immunosuppressive drugs in patient care was formed in 1999 to provide recommendations for the use in the treatment of patients with ocular inflammatory disorders as discussed by the authors.

Journal ArticleDOI
TL;DR: The authors have developed the Arizona Sexual Experiences Scale (ASEX), a five-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm.
Abstract: Although sexual dysfunction is common in psychiatric patients, quantification of sexual dysfunction is limited by the paucity of validated, user-friendly scales. In order to address this problem, the authors have developed the Arizona Sexual Experiences Scale (ASEX), a five-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Possible total scores range from 5 to 30, with the higher scores indicating more sexual dysfunction. This study assesses the internal consistency, test-retest reliability, and convergent and discriminant validity of the ASEX.