Showing papers by "University of Illinois at Chicago published in 1999"

Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology

Abstract: Molecular chaperones, including the heat-shock proteins (Hsps), are a ubiquitous feature of cells in which these proteins cope with stress-induced denaturation of other proteins. Hsps have received the most attention in model organisms undergoing experimental stress in the laboratory, and the function of Hsps at the molecular and cellular level is becoming well understood in this context. A complementary focus is now emerging on the Hsps of both model and nonmodel organisms undergoing stress in nature, on the roles of Hsps in the stress physiology of whole multicellular eukaryotes and the tissues and organs they comprise, and on the ecological and evolutionary correlates of variation in Hsps and the genes that encode them. This focus discloses that (a) expression of Hsps can occur in nature, (b) all species have hsp genes but they vary in the patterns of their expression, (c) Hsp expression can be correlated with resistance to stress, and (d) species' thresholds for Hsp expression are correlated with levels of stress that they naturally undergo. These conclusions are now well established and may require little additional confirmation; many significant questions remain unanswered concerning both the mechanisms of Hsp-mediated stress tolerance at the organismal level and the evolutionary mechanisms that have diversified the hsp genes.

Improved microbial gene identification with GLIMMER

Abstract: The GLIMMER system for microbial gene identification finds approximately 97-98% of all genes in a genome when compared with published annotation. This paper reports on two new results: (i) significant technical improvements to GLIMMER that improve its accuracy still further, and (ii) a comprehensive evaluation that demonstrates that the accuracy of the system is likely to be higher than previously recognized. A significant proportion of the genes missed by the system appear to be hypothetical proteins whose existence is only supported by the predictions of other programs. When the analysis is restricted to genes that have significant homology to genes in other organisms, GLIMMER misses <1% of known genes.

Reducing obesity via a school-based interdisciplinary intervention among youth: Planet Health

Abstract: Objective To evaluate the impact of a school-based health behavior intervention known as Planet Health on obesity among boys and girls in grades 6 to 8. Design Randomized, controlled field trial with 5 intervention and 5 control schools. Outcomes were assessed using preintervention (fall 1995) and follow-up measures (spring 1997), including prevalence, incidence, and remission of obesity. Participants A group of 1295 ethnically diverse grade 6 and 7 students from public schools in 4 Massachusetts communities. Intervention Students participated in a school-based interdisciplinary intervention over 2 school years. Planet Health sessions were included within existing curricula using classroom teachers in 4 major subjects and physical education. Sessions focused on decreasing television viewing, decreasing consumption of high-fat foods, increasing fruit and vegetable intake, and increasing moderate and vigorous physical activity. Main Outcome Measures Obesity was defined as a composite indicator based on both a body mass index and a triceps skinfold value greater than or equal to age- and sex-specific 85th percentiles. Because schools were randomized, rather than students, the generalized estimating equation method was used to adjust for individual-level covariates under cluster randomization. Results The prevalence of obesity among girls in intervention schools was reduced compared with controls, controlling for baseline obesity (odds ratio, 0.47; 95% confidence interval, 0.24-0.93; P = .03), with no differences found among boys. There was greater remission of obesity among intervention girls vs control girls (odds ratio, 2.16; 95% confidence interval, 1.07-4.35; P = .04). The intervention reduced television hours among both girls and boys, and increased fruit and vegetable consumption and resulted in a smaller increment in total energy intake among girls. Reductions in television viewing predicted obesity change and mediated the intervention effect. Among girls, each hour of reduction in television viewing predicted reduced obesity prevalence (odds ratio, 0.85; 95% confidence interval, 0.75-0.97; P = .02). Conclusion Planet Health decreased obesity among female students, indicating a promising school-based approach to reducing obesity among youth.

A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy.

Abstract: Chemotherapy and radiation therapy for cancer often have severe side effects that limit their efficacy. Because these effects are in part determined by p53-mediated apoptosis, temporary suppression of p53 has been suggested as a therapeutic strategy to prevent damage of normal tissues during treatment of p53-deficient tumors. To test this possibility, a small molecule was isolated for its ability to reversibly block p53-dependent transcriptional activation and apoptosis. This compound, pifithrin-alpha, protected mice from the lethal genotoxic stress associated with anticancer treatment without promoting the formation of tumors. Thus, inhibitors of p53 may be useful drugs for reducing the side effects of cancer therapy and other types of stress associated with p53 induction.

Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome.

Abstract: OBJECTIVE: NIDDM occurs commonly among women with polycystic ovary syndrome (PCOS). The prevalence and natural history of its precursor, impaired glucose tolerance (IGT), is less well known. The objective of this study was to characterize the prevalence and incidence of glucose intolerance in a large cohort of women with well-characterized PCOS. RESEARCH DESIGN AND METHODS: A total of 122 women with clinical and hormonal evidence of PCOS were recruited from the Medicine, Endocrinology, Gynecology, and Pediatrics Clinics at the University of Chicago. All women had a standard oral glucose tolerance test (OGTT) with measurement of glucose and insulin levels. A subset of 25 women were subsequently restudied with the aim of characterizing the natural history of glucose tolerance in PCOS. RESULTS: Glucose tolerance was abnormal in 55 (45%) of the 122 women: 43 (35%) had IGT and 12 (10%) had NIDDM at the time of initial study. The women with NIDDM differed from those with normal glucose tolerance in that they had a 2.6-fold higher prevalence of first-degree relatives with NIDDM (83 vs. 31%, P

Math1: an essential gene for the generation of inner ear hair cells.

Abstract: The mammalian inner ear contains the cochlea and vestibular organs, which are responsible for hearing and balance, respectively. The epithelia of these sensory organs contain hair cells that function as mechanoreceptors to transduce sound and head motion. The molecular mechanisms underlying hair cell development and differentiation are poorly understood. Math1, a mouse homolog of theDrosophila proneural gene atonal, is expressed in inner ear sensory epithelia. Embryonic Math1-null mice failed to generate cochlear and vestibular hair cells. This gene is thus required for the genesis of hair cells.

The Ecology of Fear: Optimal Foraging, Game Theory, and Trophic Interactions

Abstract: Mammalian predator-prey systems are behaviorally sophisticated games of stealth and fear. But, traditional mass-action models of predator prey dynamics treat individuals as behaviorally unresponsive “molecules” in Brownian motion. Foraging theory should provide the conceptual framework to envision the interaction. But, current models of predator feeding behavior generally envision a clever predator consuming large numbers of sessile and behaviorally inert prey (e.g., kangaroo rats, Dipodomys , collecting seeds from food patches). Here, we extend foraging theory to consider a predator-prey game of stealth and fear and then embed this game into the modeling of predator-prey population dynamics. The melding of the prey and predator's optimal behaviors with their population and community-level consequences constitutes the ecology of fear. The ecology of fear identifies the endpoints of a continuum of N-driven (population size) versus μ-driven (fear) systems. In N-driven systems, the major direct dynamical feedback involves predators killing prey, whereas μ-driven systems involve the indirect effects from changes in fear levels and prey catchability. In μ-driven systems, prey respond to predators by becoming more vigilant or by moving away from suspected predators. In this way, a predator (e.g., mountain lion, Puma concolor ) depletes a food patch (e.g., local herd of mule deer, Odocoileus hemionus ) by frightening prey rather than by actually killing prey. Behavior buffers the system: a reduction in predator numbers should rapidly engender less vigilant and more catchable prey. The ecology of fear explains why big fierce carnivores should be and can be rare. In carnivore systems, ignore the behavioral game at one's peril.

Alignment of whole genomes

Abstract: A new system for aligning whole genome sequences is described. Using an efficient data structure called a suffix tree, the system is able to rapidly align sequences containing millions of nucleotides. Its use is demonstrated on two strains of Mycoplasma tuberculosis, on two less similar species of Mycoplasma bacteria and on two syntenic sequences from human chromosome 12 and mouse chromosome 6. In each case it found an alignment of the input sequences, using between 30 s and 2 min of computation time. From the system output, information on single nucleotide changes, translocations and homologous genes can easily be extracted. Use of the algorithm should facilitate analysis of syntenic chromosomal regions, strain-to-strain comparisons, evolutionary comparisons and genomic duplications.

Geometry of the complex of curves I: Hyperbolicity

Abstract: The Complex of Curves on a Surface is a simplicial complex whose vertices are homotopy classes of simple closed curves, and whose simplices are sets of homotopy classes which can be realized disjointly. It is not hard to see that the complex is finite-dimensional, but locally infinite. It was introduced by Harvey as an analogy, in the context of Teichmuller space, for Tits buildings for symmetric spaces, and has been studied by Harer and Ivanov as a tool for understanding mapping class groups of surfaces. In this paper we prove that, endowed with a natural metric, the complex is hyperbolic in the sense of Gromov. In a certain sense this hyperbolicity is an explanation of why the Teichmuller space has some negative-curvature properties in spite of not being itself hyperbolic: Hyperbolicity in the Teichmuller space fails most obviously in the regions corresponding to surfaces where some curve is extremely short. The complex of curves exactly encodes the intersection patterns of this family of regions (it is the "nerve" of the family), and we show that its hyperbolicity means that the Teichmuller space is "relatively hyperbolic" with respect to this family. A similar relative hyperbolicity result is proved for the mapping class group of a surface. We also show that the action of pseudo-Anosov mapping classes on the complex is hyperbolic, with a uniform bound on translation distance.

Blockade of the Vascular Endothelial Growth Factor Stress Response Increases the Antitumor Effects of Ionizing Radiation

Abstract: The family of vascular endothelial growth factor (VEGF) proteins include potent and specific mitogens for vascular endothelial cells that function in the lation of angiogenesis Inhibition of VEGF-induced angiogenesis either by neutralizing antibodies or dominant-negative soluble receptor, blocks the growth of primary and metastatic experimental tumors Here we report that VEGF expression is induced in Lewis lung carcinomas (LLCs) both in vitro and vivo after exposure to ionizing radiation (IR) and in human tumor cell lines (Seg-1 esophageal adenocarcinoma, SQ20B squamous cell carcinoma, T98 and U87 glioblastomas, and U1 melanoma) in vitro. The biological significance of IR-induced VEGF production is supported by our finding that treatment of tumor-bearing mice (LLC, Seg-1, SQ20B, and U87) with a neutralizing antibody to VEGF-165 before irradiation is associated with a greater than additive antitumor effect. In vitro, the addition of VEGF decreases IR-induced killing of human umbilical vein endothelial cells, and the anti-VEGF treatment potentiates IR-induced lethality of human umbilical vein endothelial cells. Neither recombinant VEGF protein nor neutralizing antibody to VEGF affects the radiosensitivity of tumor cells These findings support a model in which induction of VEGF by IR contributes to the protection of tumor blood vessels from radiation-mediated cytotoxicity and thereby to tumor radioresistance.

Emotion-based choice

Abstract: In this article the authors develop a descriptive theory of choice using anticipated emotions. People are assumed to anticipate how they will feel about the outcomes of decisions and use their predictions to guide choice. The authors measure the pleasure associated with monetary outcomes of gambles and offer an account of judged pleasure called decision affect theory. Then they propose a theory of choices between gambles based on anticipated pleasure. People are assumed to choose the option with greater subjective expected pleasure. Similarities and differences between subjective expected pleasure theory and subjective expected utility theory are discussed. Emotions have powerful effects on choice. Our actual feelings of happiness, sadness, and anger both color and shape our decisions. In addition, our imagined feelings of

Electron Beam Computed Tomographic Coronary Calcium Scanning: A Review and Guidelines for Use in Asymptomatic Persons

Abstract: Coronary artery disease is the No. 1 cause of death in the developed world. Effective means of treatment such as drug therapy to lower cholesterol levels are available, but clinical application to patients at highest risk remains imprecise. Electron beam computed tomography (EBCT) has been suggested as a means to diagnose subclinical coronary disease and facilitate risk stratification, but no current interpretive consensus exists in clinical practice. We critically reviewed current, pertinent literature regarding EBCT coronary calcium scanning from a clinical perspective and, in particular, studies that evaluated it as a measure of atherosclerotic coronary disease. Additionally, we reviewed studies that quantified the EBCT "calcium score" in relationship to coronary heart disease events. The available data suggest that the EBCT calcium score can help identify persons at higher than anticipated risk of future coronary events: the greater the EBCT coronary calcium score, the greater the extent of atherosclerotic plaque disease. Based on the literature review, we offer EBCT interpretation guidelines as they relate to drug therapy and risk reduction in asymptomatic persons with borderline cholesterol levels. Considerable evidence shows that coronary calcium is specific for atherosclerotic plaque and that it can be sensitively detected and accurately quantified by using EBCT. The coronary calcium score can help guide initiation of clinical prevention programs as part of a risk stratification and management scheme aimed at improving outcomes in patients determined to be at highest risk of coronary disease for their respective age and gender.

A community-based study of chronic fatigue syndrome.

Abstract: Background: Most previous estimates of the prevalence of chronic fatigue syndrome (CFS) have derived largely from treated populations, and have been biased by differential access to health care treatment linked with sex, ethnic identification, and socioeconomic status. Objective: To assess the point prevalence of CFS in an ethnically diverse random community sample. Design and Participants: A sample of 28 673 adults in Chicago, Ill, was screened by telephone, and those with CFS-like symptoms were medically evaluated. Main Outcome Measures and Analyses: Selfreport questionnaires, psychiatric evaluations, and complete medical examinations with laboratory testing were used to diagnose patients with CFS. Univariate and multivariate statistical techniques were used to delineate the overall rate of CFS in this population, and its relative prevalence was subcategorized by sex, ethnic identification, age, and socioeconomic status. Results: There was a 65.1% completion rate for the telephone interviews during the first phase of the study. Findings indicated that CFS occurs in about 0.42% (95% confidence interval, 0.29%-0.56%) of this random community-based sample. The highest levels of CFS were consistently found among women, minority groups, and persons with lower levels of education and occupational status.

Akt/Protein Kinase B Inhibits Cell Death by Preventing the Release of Cytochrome c from Mitochondria

Abstract: Growth factors signaling through the phosphoinositide 3-kinase/Akt pathway promote cell survival. The mechanism by which the serine/threonine kinase Akt prevents cell death remains unclear. We have previously shown that Akt inhibits the activity of DEVD-targeted caspases without changing the steady-state levels of Bcl-2 and Bcl-x(L). Here we show that Akt inhibits apoptosis and the processing of procaspases to their active forms by delaying mitochondrial changes in a caspase-independent manner. Akt activation is sufficient to inhibit the release of cytochrome c from mitochondria and the alterations in the inner mitochondrial membrane potential. However, Akt cannot inhibit apoptosis induced by microinjection of cytochrome c. We also demonstrated that Akt inhibits apoptosis and cytochrome c release induced by several proapoptotic Bcl-2 family members. Taken together, our results show that Akt promotes cell survival by intervening in the apoptosis cascade before cytochrome c release and caspase activation via a mechanism that is distinct from Bad phosphorylation.

Phosphorylation of p70(S6k) correlates with increased skeletal muscle mass following resistance exercise

Abstract: High-resistance exercise training results in an increase in muscle wet mass and protein content. To begin to address the acute changes following a single bout of high-resistance exercise, a new model has been developed. Training rats twice a week for 6 wk resulted in 13.9 and 14.4% hypertrophy in the extensor digitorum longus (EDL) and tibialis anterior (TA) muscles, respectively. Polysome profiles after high-resistance lengthening contractions suggest that the rate of initiation is increased. The activity of the 70-kDa S6 protein kinase (p70(S6k)), a regulator of translation initiation, is also increased following high-resistance lengthening contractions (TA, 363 +/- 29%; EDL, 353 +/- 39%). Furthermore, the increase in p70(S6k) activity 6 h after exercise correlates with the percent change in muscle mass after 6 wk of training (r = 0.998). The tight correlation between the activation of p70(S6k) and the long-term increase in muscle mass suggests that p70(S6k) phosphorylation may be a good marker for the phenotypic changes that characterize muscle hypertrophy and may play a role in load-induced skeletal muscle growth.

Inhibition of myosin light chain kinase by p21-activated kinase.

Abstract: p21-activated kinases (PAKs) are implicated in the cytoskeletal changes induced by the Rho family of guanosine triphosphatases Cytoskeletal dynamics are primarily modulated by interactions of actin and myosin II that are regulated by myosin light chain kinase (MLCK)-mediated phosphorylation of the regulatory myosin light chain (MLC) p21-activated kinase 1 (PAK1) phosphorylates MLCK, resulting in decreased MLCK activity MLCK activity and MLC phosphorylation were decreased, and cell spreading was inhibited in baby hamster kidney-21 and HeLa cells expressing constitutively active PAK1 These data indicate that MLCK is a target for PAKs and that PAKs may regulate cytoskeletal dynamics by decreasing MLCK activity and MLC phosphorylation

Racial/ethnic group differences in the prevalence of sexually transmitted diseases in the United States: a network explanation.

Abstract: Background:Many studies have observed that African Americans have comparatively high rates of selected STDs, often 10 to 20 times higher than whites and other racial/ethnic groups, but without convincing explanation.Goal:This study attempts to solve this puzzle using data from a nationally represent

Cancer chemopreventive activity of resveratrol.

Abstract: Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a naturally occurring compound shown to inhibit carcinogen-induced preneoplastic lesion formation in mouse mammary organ culture and tumorigenesis in the two-stage mouse skin model. Cancer chemopreventive potential was also suggested in various assays reflective of the three major stages of carcinogenesis. Anti-initiation activity was indicated by its antioxidant and antimutagenic effects, inhibition of the hydroperoxidase function of cyclooxygenase (COX), and induction of phase II drug-metabolizing enzymes. Antipromotion activity was indicated by antiinflammatory effects, inhibition of production of arachidonic acid metabolites catalyzed by either COX-1 or COX-2, and chemical carcinogen-induced neoplastic transformation of mouse embryo fibroblasts. Antiprogression activity was demonstrated by its ability to induce human promyelocytic leukemia (HL-60) cell differentiation. Moreover, pretreatment of mouse skin with resveratrol significantly counteracted 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative stress, as evidenced by numerous biochemical responses. Resveratrol reduced the generation of hydrogen peroxide, and normalized levels of myeloperoxidase and oxidized-glutathione reductase activities. It also restored glutathione levels and superoxide dismutase activity. As judged by the reverse transcriptase-polymerase chain reaction, resveratrol selectively inhibited TPA-induced expression of c-fos and transforming growth factor-beta 1 (TGF-beta 1), but did not affect other TPA-induced gene products including COX-1, COX-2, c-myc, c-jun, and tumor necrosis factor-alpha. These data indicate that resveratrol may interfere with reactive oxidant pathways and/or modulate the expression of c-fos and TGF-beta 1 to inhibit tumorigenesis in mouse skin. As reported herein, in addition to the activities described above, resveratrol inhibited the de novo formation of inducible nitric oxide synthase (iNOS) in mouse macrophages stimulated with lipopolysaccharide. This finding suggests an additional mechanism by which resveratrol may function as a cancer chemopreventive agent.

Dynamics of disease resistance polymorphism at the Rpm1 locus of Arabidopsis

Abstract: The co-evolutionary 'arms race' is a widely accepted model for the evolution of host-pathogen interactions. This model predicts that variation for disease resistance will be transient, and that host populations generally will be monomorphic at disease-resistance (R-gene) loci. However, plant populations show considerable polymorphism at R-gene loci involved in pathogen recognition. Here we have tested the arms-race model in Arabidopsis thaliana by analysing sequences flanking Rpm1, a gene conferring the ability to recognize Pseudomonas pathogens carrying AvrRpm1 or AvrB. We reject the arms-race hypothesis: resistance and susceptibility alleles at this locus have co-existed for millions of years. To account for the age of alleles and the relative levels of polymorphism within allelic classes, we use coalescence theory to model the long-term accumulation of nucleotide polymorphism in the context of the short-term ecological dynamics of disease resistance. This analysis supports a 'trench warfare' hypothesis, in which advances and retreats of resistance-allele frequency maintain variation for disease resistance as a dynamic polymorphism.

Vigilance, patch use and habitat selection: Foraging under predation risk

Abstract: To balance conXicting demands for food and safety from predation, feeding animals have two useful tools. First, they can vary the amount of time they devote to harvesting patches that vary in predation risk and feeding rates. Second, they can use vigilance to trade-oV food and safety while feeding from a food patch. I present a model for predicting how an optimal forager should jointly use these two tools. Factors inXuencing the use of these tools include encounter rate with predators, predator lethality in the absence of vigilance, eVectiveness of vigilance in reducing predator lethality, the marginal value of energy to the forager and the forager’s survivor’s Wtness. Patch-use behaviours inXuenced by these factors include vigilance level, quitting harvest rate and giving-up density (GUD). All three of these patch-use behaviours should increase in response to an increase in encounter rate with predators, predator lethality and the forager’s survivor’s Wtness, and decrease with an increase in the marginal value of energy. In response to increasing the eVectiveness of vigilance, vigilance should increase and the GUD and quitting harvest rate should decline. The amount of food left by a forager in a depletable food patch, the GUD, provides an empirical link for testing the model’s predictions. Giving-up densities should increase with increasing predation risk, and GUDs should increase with declining food-densityspeciWc harvest rates. DiVerences in GUDs among food patches attributable to diVerences in quitting harvest rates measure the contribution of time allocation to managing diVerences in predation risk. DiVerences in GUDs attributable to diVerences in food-density-speciWc harvest rates measure the contribution of vigilance to managing predation risk.

A senescence-like phenotype distinguishes tumor cells that undergo terminal proliferation arrest after exposure to anticancer agents

Abstract: Exposure of human tumor cell lines to different chemotherapeutic drugs, ionizing radiation, and differentiating agents induced morphological, enzymatic, and ploidy changes resembling replicative senescence of normal cells. Moderate doses of doxorubicin induced this senescence-like phenotype (SLP) in 11 of 14 tested cell lines derived from different types of human solid tumors, including all of the lines with wild-type p53 and half of p53-mutated cell lines. SLP induction seemed to be independent from mitotic cell death, the other major effect of drug treatment. Among cells that survived drug exposure, SLP markers distinguished those cells that became terminally growth-arrested within a small number of cell divisions from the cells that recovered and resumed proliferation. SLP induction in breast carcinoma cells treated with retinoids in vitro or in vivo was found to correlate with permanent growth inhibition under the conditions of minimal cytotoxicity, suggesting that this response may be particularly important for the antiproliferative effect of differentiating agents. The senescence-like program of terminal proliferation arrest may provide an important determinant of treatment outcome and a target for augmentation in cancer therapy.

A Longitudinal Assessment of Teacher Perceptions of Parent Involvement in Children's Education and School Performance

Abstract: This study examines the ways in which parental involvement in children's education changes over time and how it relates to children's social and academic functioning in school. Teachers provided information on parent involvement and school performance for 1,205 urban, kindergarten through third-grade children for 3 consecutive years. They rated the following four dimensions of parent involvement: frequency of parent-teacher contact, quality of the parent-teacher interactions, participation in educational activities at home, and participation in school activites. As predicted, the frequency of parent-teacher contacts, quality of parent-teacher interactions, and parent participation at school declined from Years 1 to 3. Every parent involvement variable correlated moderately with school performance and parent involvement in Years 1 and 2, and accounted for a small, but significant amount of variance in Year 3 performance after controlling for initial performance level. Participation in educational activities at home predicted the widest range of performance variables. Results suggest that enhancing parental involvement in children's schooling relates to improvements in school functioning.