Showing papers by "University of New Mexico published in 2007"

Optimal Medical Therapy with or without PCI for Stable Coronary Disease

Abstract: We conducted a randomized trial involving 2287 patients who had objective evidence of myocardial ischemia and significant coronary artery disease at 50 U.S. and Canadian centers. Between 1999 and 2004, we assigned 1149 patients to undergo PCI with optimal medical therapy (PCI group) and 1138 to receive optimal medical therapy alone (medical-therapy group). The primary outcome was death from any cause and nonfatal myocardial infarction during a follow-up period of 2.5 to 7.0 years (median, 4.6). Results There were 211 primary events in the PCI group and 202 events in the medicaltherapy group. The 4.6-year cumulative primary-event rates were 19.0% in the PCI group and 18.5% in the medical-therapy group (hazard ratio for the PCI group, 1.05; 95% confidence interval [CI], 0.87 to 1.27; P = 0.62). There were no significant differences between the PCI group and the medical-therapy group in the composite of death, myocardial infarction, and stroke (20.0% vs. 19.5%; hazard ratio, 1.05; 95% CI, 0.87 to 1.27; P = 0.62); hospitalization for acute coronary syndrome (12.4% vs. 11.8%; hazard ratio, 1.07; 95% CI, 0.84 to 1.37; P = 0.56); or myocardial infarction (13.2% vs. 12.3%; hazard ratio, 1.13; 95% CI, 0.89 to 1.43; P = 0.33). Conclusions As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy. (ClinicalTrials.gov number, NCT00007657.)

Guidelines of the american society of mammalogists for the use of wild mammals in research

Abstract: General guidelines for use of wild mammal species are updated from the 1998 version approved by the American Society of Mammalogists (ASM) and expanded to include additional resources. Included are details on marking, housing, trapping, and collecting mammals. These guidelines cover current professional techniques and regulations involving mammals used in research. Institutional animal care and use committees, regulatory agencies, and investigators should review and approve procedures concerning use of vertebrates at any particular institution. These guidelines were prepared and approved by the ASM, whose collective expertise provides a broad and comprehensive understanding of the biology of nondomesticated mammals in their natural environments.

Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases.

Abstract: Background A phase 3 trial was conducted to evaluate the efficacy of a prophylactic quadrivalent vaccine in preventing anogenital diseases associated with human papillomavirus (HPV) types 6, 11, 16, and 18. Methods In this randomized, placebo-controlled, double-blind trial involving 5455 women between the ages of 16 and 24 years, we assigned 2723 women to receive vaccine and 2732 to receive placebo at day 1, month 2, and month 6. The coprimary composite end points were the incidence of genital warts, vulvar or vaginal intraepithelial neoplasia, or cancer and the incidence of cervical intraepithelial neoplasia, adenocarcinoma in situ, or cancer associated with HPV type 6, 11, 16, or 18. Data for the primary analysis were collected for a per-protocol susceptible population of women who had no virologic evidence of HPV type 6, 11, 16, or 18 through 1 month after administration of the third dose. Results The women were followed for an average of 3 years after administration of the first dose. In the per-proto...

Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia.

Abstract: Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P = 0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups. Conclusions Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597.)

Interactive Multimodal Learning Environments Special Issue on Interactive Learning Environments: Contemporary Issues and Trends

Abstract: What are interactive multimodal learning environments and how should they be designed to promote students’ learning? In this paper, we offer a cognitive–affective theory of learning with media from which instructional design principles are derived. Then, we review a set of experimental studies in which we found empirical support for five design principles: guided activity, reflection, feedback, control, and pretraining. Finally, we offer directions for future instructional technology research.

Motivational Interviewing in Health Care: Helping Patients Change Behavior

Abstract: Behavior change is a critical part of effective health care. The final decision to become healthier, however, is that of the patient and not the practitioner. Anyone who has treated patients knows ...

The visual scoring of sleep in adults

Abstract: The 1968 Rechtschaffen and Kales (R & K) sleep scoring man- ual was published 15 years after REM sleep was discovered. Advances in the ensuing 28 years warranted a re-look at visual scoring of sleep stages. This paper describes the work of the AASM Visual Scoring Task Force, including methodology, a literature review and the rationale behind the new rules. Reliability studies of R & K scoring were reviewed; reliabil- ity was low for stage one and moderate for slow wave sleep. Evidence indicated that K complexes and slow waves are expressed maximal fron- tally, spindles centrally and alpha rhythm over the occipital region. Three derivations of EEG, two of electro-oculography, and one of chin EMG were recommended. Scoring by 30-second epochs was retained. New terminology for sleep stages was proposed. Attenuation of alpha rhythm was determined to be the most valid electrophysiological marker of sleep onset. Alternative measures were proposed for non-alpha generating subjects. K complexes associated with arousals were determined to be insufficient alone to define the new stage N2. No evidence was found to justify dividing slow wave sleep into two stages. No reasons were found to alter the current slow wave amplitude criteria at any age. The phenomena of REM sleep were defined. The rules for defining onset and termination of REM sleep periods were simplified. Movement time was eliminated and major body movements defined. Studies are needed to test the reliability of the new rules. Future advances in technology may require modification of these rules with time.

Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat

Abstract: Matrix metalloproteinases (MMPs) disrupt the blood-brain barrier (BBB) during reperfusion. Occludin and claudins are recently described tight junction proteins (TJPs) that form the BBB. We hypothesized that the opening of the BBB was because of the degradation of TJPs by the MMPs. Spontaneously hypertensive rats had a 90 mins middle cerebral artery occlusion with reperfusion for 2, 3, or 24 h. Matrix metalloproteinases were measured by immunohistochemistry and in situ and gel zymography. Real-time polymerase chain reaction (PCR) measured mRNAs of MMP-2 and -9, furin, membrane-type MMP (MT1-MMP), occludin, and claudin-5. There was opening of the BBB in the piriform cortex after 3 h of reperfusion, and an MMP inhibitor, BB-1101 (30 mg/kg), prevented the opening. At 3 h, in situ zymograms showed gelatinase activity. Zymography and PCR showed greater increases in MMP-2 than in MMP-9. There were increased mRNA and immunohistochemistry for MT1-MMP and furin, which activate MMP-2. Claudin-5 and occludin mRNA expression decreased at 2 h in both hemispheres with fragments of both proteins seen on Western blot by 3 h on the ischemic side; treatment with BB-1101 reversed the degradation of the TJPs. Immunohistochemistry at 3 h showed fragmented TJPs within the endothelial cell clefts. By 24 h, in situ zymography showed gelatinase activity and gel zymography showed elevated levels of MMP-9. Disrupted TJPs previously seen in endothelial cells appeared in the surrounding astrocytes. Our results provide direct evidence that MMPs open the BBB by degrading TJPs and that an MMP inhibitor prevents degradation of the TJPs by MMPs.

Unveiling the roles of autophagy in innate and adaptive immunity

Abstract: Cells digest portions of their interiors in a process known as autophagy to recycle nutrients, remodel and dispose of unwanted cytoplasmic constituents. This ancient pathway, conserved from yeast to humans, is now emerging as a central player in the immunological control of bacterial, parasitic and viral infections. The process of autophagy may degrade intracellular pathogens, deliver endogenous antigens to MHC-class-II-loading compartments, direct viral nucleic acids to Toll-like receptors and regulate T-cell homeostasis. This Review describes the mechanisms of autophagy and highlights recent advances relevant to the role of autophagy in innate and adaptive immunity.

Ecological and evolutionary insights from species invasions

Abstract: Species invasions provide numerous unplanned and frequently, but imperfectly, replicated experiments that can be used to better understand the natural world. Classic studies by Darwin, Grinnell, Elton and others on these species-invasion experiments provided invaluable insights for ecology and evolutionary biology. Recent studies of invasions have resulted in additional insights, six of which we discuss here; these insights highlight the utility of using exotic species as 'model organisms'. We also discuss a nascent hypothesis that might provide a more general, predictive understanding of invasions and community assembly. Finally, we emphasize how the study of invasions can help to inform our understanding of applied problems, such as extinction, ecosystem function and the response of species to climate change.

Correlation of the highest-energy cosmic rays with nearby extragalactic objects.

Abstract: Using data collected at the Pierre Auger Observatory during the past 3.7 years, we demonstrate that there is a correlation between the arrival directions of cosmic rays with energy above {approx} 6 x 10{sup 19} eV and the positions of active galactic nuclei (AGN) lying within {approx} 75 Mpc. We reject the hypothesis of an isotropic distribution of these cosmic rays at over 99% confidence level from a prescribed a priori test. The correlation we observe is compatible with the hypothesis that the highest energy particles originate from nearby extragalactic sources whose flux has not been significantly reduced by interaction with the cosmic background radiation. AGN or objects having a similar spatial distribution are possible sources.

Power-law distributions in empirical data

Abstract: Power-law distributions occur in many situations of scientific interest and have significant consequences for our understanding of natural and man-made phenomena. Unfortunately, the detection and characterization of power laws is complicated by the large fluctuations that occur in the tail of the distribution -- the part of the distribution representing large but rare events -- and by the difficulty of identifying the range over which power-law behavior holds. Commonly used methods for analyzing power-law data, such as least-squares fitting, can produce substantially inaccurate estimates of parameters for power-law distributions, and even in cases where such methods return accurate answers they are still unsatisfactory because they give no indication of whether the data obey a power law at all. Here we present a principled statistical framework for discerning and quantifying power-law behavior in empirical data. Our approach combines maximum-likelihood fitting methods with goodness-of-fit tests based on the Kolmogorov-Smirnov statistic and likelihood ratios. We evaluate the effectiveness of the approach with tests on synthetic data and give critical comparisons to previous approaches. We also apply the proposed methods to twenty-four real-world data sets from a range of different disciplines, each of which has been conjectured to follow a power-law distribution. In some cases we find these conjectures to be consistent with the data while in others the power law is ruled out.

Tectonic model for the Proterozoic growth of North America

Abstract: This paper presents a plate-scale model for the Precambrian growth and evolution of the North American continent. The core of the North American continent (Canadian shield) came together in the Paleoproterozoic (2.0–1.8 Ga) by plate collisions of Archean continents (Slave with Rae-Hearne, then Rae-Hearne with Superior) as well as smaller Archean continental fragments (Wyoming, Medicine Hat, Sask, Marshfield, Nain cratons). The resulting Trans-Hudson orogen was a collisional belt similar in scale to the modern Himalayas. It contains mainly reworked Archean crust, but remnants of juvenile volcanic belts are preserved between Archean masses. The thick, buoyant, and compositionally depleted mantle lithosphere that now underlies North America, although dominantly of Archean age, took its present shape by processes of collisional orogenesis and likely has a scale of mantle heterogeneity similar to that exhibited in the overlying crust. In marked contrast, lithosphere of southern North America (much of the conti nental United States) was built by progressive addition of a series of dominantly juvenile vol canic arcs and oceanic terranes accreted along a long-lived southern (present coordinates) plate margin. Early juvenile additions (Pembine-Wausau, Elves Chasmarcs) formed at the same time (1.84–1.82 Ga) the core was assembling. Following final assembly of the Archean and Paleoproterozoic core of North America by 1.8 Ga, major accretionary provinces (defined mainly by isotopic model ages) were added by arc-continent accretion, analogous to present-day convergence between Australia and Indonesia. Also similar to Indonesia, some accreted terranes contain older continental crustal material [Archean(?) Mojavia], but the extent and geometry of older crust are not well known. Accretionary provinces are composed of numerous 10 to 100 km scale terranes or blocks, separated by shear zones, some of which had compound histories as terrane sutures and later crustal-assembly structures. Major northeast-trending provinces are the Yavapai province (1.80–1.70 Ga), welded to North America during the 1.71–1.68 Ga Yavapai orogeny; the Mazatzal province (1.70–1.65 Ga), added during the 1.65–1.60 Ga Mazatzal orogeny; the Granite-Rhyolite province (1.50–1.30 Ga), added during the 1.45–1.30 Ga tectonic event associated with A-type intracratonic magmatism; and the Llano-Grenville province (1.30–1.00 Ga), added during the 1.30–0.95 Ga broader Grenville orogeny. During each episode of addition of juvenile lithosphere, the transformation of juvenile crust into stable continental lithosphere was facilitated by voluminous granitoid plutonism that stitched new and existing orogenic boundaries. Slab roll back created transient extensional basins (1.70 and 1.65 Ga) in which Paleoproterozoic quartzite-rhyolite successions were deposited, then thrust imbricated as basins were inverted. The lithospheric collage that formed from dominantly juvenile terrane accretion and stabilization (1.8–1.0 Ga) makes up about half of the present-day North American continent. Throughout (and as a result of) this long-lived convergent cycle, mantle lithosphere below the accretionary provinces was more hydrous, fertile, and relatively weak compared to mantle lithosphere under the Archean core.

Consensus Statement for Standard of Care in Spinal Muscular Atrophy

Abstract: Spinal muscular atrophy is a neurodegenerative disease that requires multidisciplinary medical care. Recent progress in the understanding of molecular pathogenesis of spinal muscular atrophy and advances in medical technology have not been matched by similar developments in the care for spinal muscular atrophy patients. Variations in medical practice coupled with differences in family resources and values have resulted in variable clinical outcomes that are likely to compromise valid measure of treatment effects during clinical trials. The International Standard of Care Committee for Spinal Muscular Atrophy was formed in 2005, with a goal of establishing practice guidelines for clinical care of these patients. The 12 core committee members worked with more than 60 spinal muscular atrophy experts in the field through conference calls, e-mail communications, a Delphi survey, and 2 in-person meetings to achieve consensus on 5 care areas: diagnostic/new interventions, pulmonary, gastrointestinal/nutrition, orthopedics/rehabilitation, and palliative care. Consensus was achieved on several topics related to common medical problems in spinal muscular atrophy, diagnostic strategies, recommendations for assessment and monitoring, and therapeutic interventions in each care area. A consensus statement was drafted to address the 5 care areas according to 3 functional levels of the patients: nonsitter, sitter, and walker. The committee also identified several medical practices lacking consensus and warranting further investigation. It is the authors' intention that this document be used as a guideline, not as a practice standard for their care. A practice standard for spinal muscular atrophy is urgently needed to help with the multidisciplinary care of these patients.

Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences

Abstract: We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.

Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures

Abstract: Sequencing of multiple related species followed by comparative genomics analysis constitutes a powerful approach for the systematic understanding of any genome. Here, we use the genomes of 12 Drosophila species for the de novo discovery of functional elements in the fly. Each type of functional element shows characteristic patterns of change, or 'evolutionary signatures', dictated by its precise selective constraints. Such signatures enable recognition of new protein-coding genes and exons, spurious and incorrect gene annotations, and numerous unusual gene structures, including abundant stop-codon readthrough. Similarly, we predict non-protein-coding RNA genes and structures, and new microRNA (miRNA) genes. We provide evidence of miRNA processing and functionality from both hairpin arms and both DNA strands. We identify several classes of pre- and post-transcriptional regulatory motifs, and predict individual motif instances with high confidence. We also study how discovery power scales with the divergence and number of species compared, and we provide general guidelines for comparative studies.

Burned by Bullying in the American Workplace: Prevalence, Perception, Degree and Impact†

Abstract: This study assesses the prevalence of workplace bullying in a sample of US workers, using a standardized measure of workplace bullying (Negative Acts Questionnaire, NAQ), and compares the current study's prevalence rates with those from other bullying and aggression studies. The article opens by defining bullying as a persistent, enduring form of abuse at work and contrasting it with other negative workplace actions and interactions. Through a review of the current literature, we propose and test hypotheses regarding bullying prevalence and dynamics relative to a sample of US workers. After discussing research methods, we report on the rates of bullying in a US sample, compare these to similar studies, and analyse the negative acts that might lead to perceptions of being bullied. Based upon past conceptualizations, as well as research that suggests bullying is a phenomenon that occurs in gradations, we introduce and provide statistical evidence for the construct and impact of bullying degree. Finally, the study explores the impact of bullying on persons who witnessed but did not directly experience bullying in their jobs.

Annual report to the nation on the status of cancer, 1975-2004, featuring cancer in American Indians and Alaska Natives.

Abstract: BACKGROUND. The American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate annually to provide updated information on cancer occurrence and trends in the U.S. The 2007 report features a comprehensive compilation of cancer information for American Indians and Alaska Natives (AI/AN). METHODS. Cancer incidence data were available for up to 82% of the U.S. population. Cancer deaths were available for the entire U.S. population. Long-term (1975 through 2004) and fixed-interval (1995 through 2004) incidence and mortality trends were evaluated by annual percent change using regression analyses (2-sided P < .05). Cancer screening, risk factors, socioeconomic characteristics, incidence data, and stage were compiled for non-Hispanic whites (NHW) and AI/AN across 6 regions of the U.S. RESULTS. Overall cancer death rates decreased by 2.1% per year from 2002 through 2004, nearly twice the annual decrease of 1.1% per year from 1993 through 2002. Among men and women, death rates declined for most cancers. Among women, lung cancer incidence rates no longer were increasing and death rates, although they still were increasing slightly, were increasing at a much slower rate than in the past. Breast cancer incidence rates in women decreased 3.5% per year from 2001 to 2004, the first decrease observed in 20 years. Colorectal cancer incidence and death rates and prostate cancer death rates declined, with colorectal cancer death rates dropping more sharply from 2002 through 2004. Overall, rates for AI/AN were lower than for NHW from 1999 through 2004 for most cancers, but they were higher for cancers of the stomach, liver, cervix, kidney, and gallbladder. Regional analyses, however, revealed high rates for AI/AN in the Northern and Southern Plains and Alaska. For cancers of the breast, colon and rectum, prostate, and cervix, AI/AN were less likely than NHW to be diagnosed at localized stages. CONCLUSIONS. For all races/ethnicities combined in the U.S., favorable trends in incidence and mortality were noted for lung and colorectal cancer in men and women and for breast cancer in women. For the AI/AN population, lower overall cancer incidence and death rates obscured important variations by geographic regions and less favorable healthcare access and socioeconomic status. Enhanced tobacco control and cancer screening, especially in the Northern and Southern Plains and Alaska, emerged as clear priorities. Cancer 2007;110:2119–52. Published 2007 by the American Cancer Society.

Growth and Governance: Models, Measures, and Mechanisms

Abstract: The regnant scholarly consensus linking good governance—the quality of public administration—to economic development has undergone surprisingly little empirical scrutiny. We examine the relationship by asking two questions: How confident are we in our cross-national measures of good governance? How solid are the empirical foundations of the growth-governance causal linkage? Our results suggest that the dominant measures of governance are problematic, suffering from perceptual biases, adverse selection in sampling, and conceptual conflation with economic policy choices. Within the limits of somewhat problematic measures, the evidence suggests that there is far more reason to believe that growth and development spur improvements in governance than vice versa. The policy implications are profound, for international organizations and governments are beginning to condition developmental aid on problematic measures of administrative performance.

Genetic Variation and Population Structure in Native Americans

Abstract: We examined genetic diversity and population structure in the American landmass using 678 autosomal microsatellite markers genotyped in 422 individuals representing 24 Native American populations sampled from North, Central, and South America. These data were analyzed jointly with similar data available in 54 other indigenous populations worldwide, including an additional five Native American groups. The Native American populations have lower genetic diversity and greater differentiation than populations from other continental regions. We observe gradients both of decreasing genetic diversity as a function of geographic distance from the Bering Strait and of decreasing genetic similarity to Siberians—signals of the southward dispersal of human populations from the northwestern tip of the Americas. We also observe evidence of: (1) a higher level of diversity and lower level of population structure in western South America compared to eastern South America, (2) a relative lack of differentiation between Mesoamerican and Andean populations, (3) a scenario in which coastal routes were easier for migrating peoples to traverse in comparison with inland routes, and (4) a partial agreement on a local scale between genetic similarity and the linguistic classification of populations. These findings offer new insights into the process of population dispersal and differentiation during the peopling of the Americas.

Emotional Development: Action, Communication, and Understanding

Abstract: The chapter begins by addressing the theoretical platform endorsed by the authors that consists of an integration of functionalist perspectives with dynamic systems and social contextualism. This integrated perspective entails a flexible approach to emotional behavior: Expressive behavior, action tendencies, and cultural influence on emotion meaning all have their place in understanding emotional development. The chapter goes on to examine early emotional development, highlighting the importance of emotion communication as evidenced in infants through their emotional signaling to caregivers, their social referencing to significant others, and their growing skills at affective sharing with others. The final half of the chapter examines the development of eight specific skills of emotional competence, emphasizing their social effectiveness and individual adaptiveness. We conclude with a discussion of future research directions, including what may be the relational limits of emotion, individual differences in emotional responsiveness to contextual cues, attention processes, and emotion-related goals, some of which may become interiorized with development. Keywords: adolescent development; childhood development; emotion; emotional competence; functionalism; infanct development; social context; social effectiveness

Blatant benevolence and conspicuous consumption: When romantic motives elicit strategic costly signals.

Abstract: Conspicuous displays of consumption and benevolence might serve as “costly signals” of desirable mate qualities. If so, they should vary strategically with manipulations of mating-related motives. The authors examined this possibility in 4 experiments. Inducing mating goals in men increased their willingness to spend on conspicuous luxuries but not on basic necessities. In women, mating goals boosted public—but not private—helping. Although mating motivation did not generally inspire helping in men, it did induce more helpfulness in contexts in which they could display heroism or dominance. Conversely, although mating motivation did not lead women to conspicuously consume, it did lead women to spend more publicly on helpful causes. Overall, romantic motives seem to produce highly strategic and sex-specific self-presentations best understood within a costly signaling framework.

The evolutionary genetics of personality

Abstract: Genetic influences on personality differences are ubiquitous, but their nature is not well understood. A theoretical framework might help, and can be provided by evolutionary genetics. We assess three evolutionary genetic mechanisms that could explain genetic variance in personality differences: selective neutrality, mutation-selection balance, and balancing selection. Based on evolutionary genetic theory and empirical results from behaviour genetics and personality psychology, we conclude that selective neutrality is largely irrelevant, that mutation-selection balance seems best at explaining genetic variance in intelligence, and that balancing selection by environmental heterogeneity seems best at explaining genetic variance in personality traits. We propose a general model of heritable personality differences that conceptualises intelligence as fitness components and personality traits as individual reaction norms of genotypes across environments, with different fitness consequences in different environmental niches. We also discuss the place of mental health in the model. This evolutionary genetic framework highlights the role of gene-environment interactions in the study of personality, yields new insight into the person-situation-debate and the structure of personality, and has practical implications for both quantitative and molecular genetic studies of personality. Copyright # 2007 John Wiley & Sons, Ltd.

IL-1β Causes an Increase in Intestinal Epithelial Tight Junction Permeability

Abstract: IL-1β is a prototypical proinflammatory cytokine that plays a central role in the intestinal inflammation amplification cascade. Recent studies have indicated that a TNF-α- and IFN-γ-induced increase in intestinal epithelial paracellular permeability may be an important mechanism contributing to intestinal inflammation. Despite its central role in promoting intestinal inflammation, the role of IL-1β on intestinal epithelial tight junction (TJ) barrier function remains unclear. The major aims of this study were to determine the effect of IL-1β on intestinal epithelial TJ permeability and to elucidate the mechanisms involved in this process, using a well-established in vitro intestinal epithelial model system consisting of filter-grown Caco-2 intestinal epithelial monolayers. IL-1β (0–100 ng/ml) produced a concentration- and time-dependent decrease in Caco-2 transepithelial resistance. Conversely, IL-1β caused a progressive time-dependent increase in transepithelial permeability to paracellular marker inulin. IL-1β-induced increase in Caco-2 TJ permeability was accompanied by a rapid activation of NF-κB. NF-κB inhibitors, pyrrolidine dithiocarbamate and curcumin, prevented the IL-1β-induced increase in Caco-2 TJ permeability. To further confirm the role of NF-κB in the IL-1β-induced increase in Caco-2 TJ permeability, NF-κB p65 expression was silenced by small interfering RNA transfection. NF-κB p65 depletion completely inhibited the IL-1β-induced increase in Caco-2 TJ permeability. IL-1β did not induce apoptosis in the Caco-2 cell. In conclusion, our findings show for the first time that IL-1β at physiologically relevant concentrations causes an increase in intestinal epithelial TJ permeability. The IL-1β-induced increase in Caco-2 TJ permeability was mediated in part by the activation of NF-κB pathways but not apoptosis.