Showing papers by "University of Illinois at Chicago published in 2005"
TL;DR: From an analysis of the effect of obesity on longevity, it is concluded that the steady rise in life expectancy during the past two centuries may soon come to an end.
Abstract: Forecasts of life expectancy are an important component of public policy that influence age-based entitlement programs such as Social Security and Medicare. Although the Social Security Administration recently raised its estimates of how long Americans are going to live in the 21st century, current trends in obesity in the United States suggest that these estimates may not be accurate. From our analysis of the effect of obesity on longevity, we conclude that the steady rise in life expectancy during the past two centuries may soon come to an end.
2,798 citations
TL;DR: White adipose tissue is no longer considered an inert tissue mainly devoted to energy storage but is emerging as an active participant in regulating physiologic and pathologic processes, including immunity and inflammation.
Abstract: White adipose tissue is no longer considered an inert tissue mainly devoted to energy storage but is emerging as an active participant in regulating physiologic and pathologic processes, including immunity and inflammation. Macrophages are components of adipose tissue and actively participate in its activities. Furthermore, cross-talk between lymphocytes and adipocytes can lead to immune regulation. Adipose tissue produces and releases a variety of proinflammatory and anti-inflammatory factors, including the adipokines leptin, adiponectin, resistin, and visfatin, as well as cytokines and chemokines, such as TNF-α, IL-6, monocyte chemoattractant protein 1, and others. Proinflammatory molecules produced by adipose tissue have been implicated as active participants in the development of insulin resistance and the increased risk of cardiovascular disease associated with obesity. In contrast, reduced leptin levels might predispose to increased susceptibility to infection caused by reduced T-cell responses in malnourished individuals. Altered adipokine levels have been observed in a variety of inflammatory conditions, although their pathogenic role has not been completely clarified.
2,482 citations
TL;DR: The genesis of these tasks is reviewed and how and why they came to be so influential, the reliability and validity of the tasks are addressed, and more technical aspects are considered, such as optimal administration and scoring procedures.
Abstract: Working memory (WM) span tasks—and in particular, counting span, operation span, and reading span tasks—are widely used measures of WM capacity. Despite their popularity, however, there has never been a comprehensive analysis of the merits of WM span tasks as measurement tools. Here, we review the genesis of these tasks and discuss how and why they came to be so influential. In so doing, we address the reliability and validity of the tasks, and we consider more technical aspects of the tasks, such as optimal administration and scoring procedures. Finally, we discuss statistical and methodological techniques that have commonly been used in conjunction with WM span tasks, such as latent variable analysis and extreme-groups designs.
2,411 citations
TL;DR: The results showed that the effects of perceived learning from entrepreneurship-related courses, previous entrepreneurial experience, and risk propensity on entrepreneurial intentions were fully mediated by entrepreneurial self-efficacy.
Abstract: The purpose of this study was to investigate the mediating role of self-efficacy in the development of students' intentions to become entrepreneurs. The authors used structural equation modeling with a sample of 265 master of business administration students across 5 universities to test their hypotheses. The results showed that the effects of perceived learning from entrepreneurship-related courses, previous entrepreneurial experience, and risk propensity on entrepreneurial intentions were fully mediated by entrepreneurial self-efficacy. Contrary to expectations, gender was not mediated by self-efficacy but had a direct effect such that women reported lower entrepreneurial career intentions. The authors discuss practical implications and directions for future research.
2,317 citations
TL;DR: In the most central Au+Au collisions at the highest beam energy, evidence is found for the formation of a very high energy density system whose description in terms of simple hadronic degrees of freedom is inappropriate as discussed by the authors.
1,786 citations
10 May 2005
TL;DR: A novel framework for analyzing and comparing consumer opinions of competing products is proposed, and a new technique based on language pattern mining is proposed to extract product features from Pros and Cons in a particular type of reviews.
Abstract: The Web has become an excellent source for gathering consumer opinions. There are now numerous Web sites containing such opinions, e.g., customer reviews of products, forums, discussion groups, and blogs. This paper focuses on online customer reviews of products. It makes two contributions. First, it proposes a novel framework for analyzing and comparing consumer opinions of competing products. A prototype system called Opinion Observer is also implemented. The system is such that with a single glance of its visualization, the user is able to clearly see the strengths and weaknesses of each product in the minds of consumers in terms of various product features. This comparison is useful to both potential customers and product manufacturers. For a potential customer, he/she can see a visual side-by-side and feature-by-feature comparison of consumer opinions on these products, which helps him/her to decide which product to buy. For a product manufacturer, the comparison enables it to easily gather marketing intelligence and product benchmarking information. Second, a new technique based on language pattern mining is proposed to extract product features from Pros and Cons in a particular type of reviews. Such features form the basis for the above comparison. Experimental results show that the technique is highly effective and outperform existing methods significantly.
1,758 citations
TL;DR: Several compounds from tropical rainforest plant species with potential anticancer activity have been identified and several compounds, mainly from edible plant species or plants used as dietary supplements, that may act as chemopreventive agents are isolated.
1,591 citations
TL;DR: There is substantial evidence to support cognitive rehabilitation for people with TBI, including strategyTraining for mild memory impairment, strategy training for postacute attention deficits, and interventions for functional communication deficits.
1,390 citations
TL;DR: These Standards will inform efforts in the field to find prevention Programs and policies that are of proven efficacy, effectiveness, or readiness for adoption and will guide prevention scientists as they seek to discover, research, and bring to the field new prevention programs and policies.
Abstract: Ever increasing demands for accountability, together with the proliferation of lists of evidence-based prevention programs and policies, led the Society for Prevention Research to charge a committee with establishing standards for identifying effective prevention programs and policies. Recognizing that interventions that are effective and ready for dissemination are a subset of effective programs and policies, and that effective programs and policies are a subset of efficacious interventions, SPR’s Standards Committee developed overlapping sets of standards. We designed these Standards to assist practitioners, policy makers, and administrators to determine which interventions are efficacious, which are effective, and which are ready for dissemination. Under these Standards, an efficacious intervention will have been tested in at least two rigorous trials that (1) involved defined samples from defined populations, (2) used psychometrically sound measures and data collection procedures; (3) analyzed their data with rigorous statistical approaches; (4) showed consistent positive effects (without serious iatrogenic effects); and (5) reported at least one significant long-term follow-up. An effective intervention under these Standards will not only meet all standards for efficacious interventions, but also will have (1) manuals, appropriate training, and technical support available to allow third parties to adopt and implement the intervention; (2) been evaluated under real-world conditions in studies that included sound measurement of the level of implementation and engagement of the target audience (in both the intervention and control conditions); (3) indicated the practical importance of intervention outcome effects; and (4) clearly demonstrated to whom intervention findings can be generalized. An intervention recognized as ready for broad dissemination under these Standards will not only meet all standards for efficacious and effective interventions, but will also provide (1) evidence of the ability to “go to scale”; (2) clear cost information; and (3) monitoring and evaluation tools so that adopting agencies can monitor or evaluate how well the intervention works in their settings. Finally, the Standards Committee identified possible standards desirable for current and future areas of prevention science as the field develops. If successful, these Standards will inform efforts in the field to find prevention programs and policies that are of proven efficacy, effectiveness, or readiness for adoption and will guide prevention scientists as they seek to discover, research, and bring to the field new prevention programs and policies.
1,264 citations
TL;DR: The framework is a holographic version of the QCD sum rules, motivated by the anti-de Sitter/conformal field theory correspondence, and naturally incorporates properties of QCD dictated by chiral symmetry.
Abstract: We propose a five-dimensional framework for modeling low-energy properties of QCD. In the simplest three parameter model we compute masses, decay rates and couplings of the lightest mesons. The model fits experimental data to within 10%. The framework is a holographic version of the QCD sum rules, motivated by the anti-de Sitter/conformal field theory correspondence. The model naturally incorporates properties of QCD dictated by chiral symmetry, which we demonstrate by deriving the Gell-Mann-Oakes-Renner relationship for the pion mass.
1,179 citations
TL;DR: Both overall and abdominal adiposity strongly and independently predict risk of type 2 diabetes.
TL;DR: It is argued that the critical aspect of successful WM measures is that rehearsal and grouping processes are prevented, allowing a clearer estimate of how many separate chunks of information the focus of attention circumscribes at once.
01 May 2005
TL;DR: In this paper, a survey and evaluation of clock synchronization protocols based on a palette of factors such as precision, accuracy, cost, and complexity is presented, which can help developers either in choosing an existing synchronization protocol or in defining a new protocol that is best suited to the specific needs of a sensor network application.
Abstract: Recent advances in micro-electromechanical (MEMS) technology have led to the development of small, low-cost, and low-power sensors Wireless sensor networks (WSNs) are large-scale networks of such sensors, dedicated to observing and monitoring various aspects of the physical world In such networks, data from each sensor is agglomerated using data fusion to form a single meaningful result, which makes time synchronization between sensors highly desirable This paper surveys and evaluates existing clock synchronization protocols based on a palette of factors like precision, accuracy, cost, and complexity The design considerations presented here can help developers either in choosing an existing synchronization protocol or in defining a new protocol that is best suited to the specific needs of a sensor-network application Finally, the survey provides a valuable framework by which designers can compare new and existing synchronization protocols
TL;DR: Racial residential segregation disproportionately places African Americans in more-impoverished neighborhoods in Detroit and consequently reduces access to supermarkets, however, supermarkets have opened or remained open close to middle-income neighborhoods that have transitioned from White to African American.
Abstract: OBJECTIVES: We evaluated the spatial accessibility of large "chain" supermarkets in relation to neighborhood racial composition and poverty.
METHODS: We used a geographic information system to measure Manhattan block distance to the nearest supermarket for 869 neighborhoods (census tracts) in metropolitan Detroit. We constructed moving average spatial regression models to adjust for spatial autocorrelation and to test for the effect of modification of percentage African American and percentage poor on distance to the nearest supermarket.
RESULTS: Distance to the nearest supermarket was similar among the least impoverished neighborhoods, regardless of racial composition. Among the most impoverished neighborhoods, however, neighborhoods in which African Americans resided were, on average, 1.1 miles further from the nearest supermarket than were White neighborhoods.
CONCLUSIONS: Racial residential segregation disproportionately places African Americans in more-impoverished neighborhoods in Detroit and consequently reduces access to supermarkets. However, supermarkets have opened or remained open close to middle-income neighborhoods that have transitioned from White to African American. Development of economically disadvantaged African American neighborhoods is critical to effectively prevent diet-related diseases among this population.
TL;DR: In this paper, the authors examine the relationship between a firm's entrepreneurial orientation and its overall performance and find that firms that follow a strategy of corporate entrepreneurship are able to pursue growth through new venture opportunities and strategic renewal.
Abstract: This article discusses research that examines the relationship between a firm's entrepreneurial orientation and their overall performance. The authors note that firms that follow a strategy of corporate entrepreneurship are able to pursue growth through new venture opportunities and strategic renewal. Firms that are able to effectively follow this strategy experience sustainable advantages and yield above-average returns. They outline and discuss five dimensions of corporate entrepreneurship including autonomy, innovativness, proactiveness, competitive aggressiveness and risk-taking. They examine what implications these strategies have for managers and identify areas of future research.
TL;DR: The results indicate that CREB phosphorylation alone is not a reliable predictor of target gene activation and that additional CREB regulatory partners are required for recruitment of the transcriptional apparatus to the promoter.
Abstract: Hormones and nutrients often induce genetic programs via signaling pathways that interface with gene-specific activators. Activation of the cAMP pathway, for example, stimulates cellular gene expression by means of the PKA-mediated phosphorylation of cAMP-response element binding protein (CREB) at Ser-133. Here, we use genome-wide approaches to characterize target genes that are regulated by CREB in different cellular contexts. CREB was found to occupy ≈4,000 promoter sites in vivo, depending on the presence and methylation state of consensus cAMP response elements near the promoter. The profiles for CREB occupancy were very similar in different human tissues, and exposure to a cAMP agonist stimulated CREB phosphorylation over a majority of these sites. Only a small proportion of CREB target genes was induced by cAMP in any cell type, however, due in part to the preferential recruitment of the coactivator CREB-binding protein to those promoters. These results indicate that CREB phosphorylation alone is not a reliable predictor of target gene activation and that additional CREB regulatory partners are required for recruitment of the transcriptional apparatus to the promoter.
TL;DR: Cotransplantation of HLA-identical sibling culture-expanded MSCs with an HLA and hematopoietic HSC transplant is feasible and seems to be safe, without immediate infusional or late MSC-associated toxicities.
TL;DR: This review focuses on transcriptional repression of p21 by cellular and viral factors, and delve in detail into its possible biological implications and its role in cancer.
Abstract: The cyclin-dependent kinase inhibitor p21WAF1/CIP1 is a major player in cell cycle control and it is mainly regulated at the transcriptional level. Whereas induction of p21 predominantly leads to cell cycle arrest, repression of p21 may have a variety of outcomes depending on the context. In this review, we concentrate on transcriptional repression of p21 by cellular and viral factors, and delve in detail into its possible biological implications and its role in cancer. It seems that the major mode of p21 transcriptional repression by negative regulators is the interference with positive transcription factors without direct binding to the p21 promoter. Specifically, the negative factors may either inhibit binding of positive regulators to the promoter or hinder their transcriptional activity. The ability of p21 to inhibit proliferation may contribute to its tumor suppressor function. Because of this, it is not surprising that a number of oncogenes repress p21 to promote cell growth and tumorigenesis. However, p21 is also an inhibitor of apoptosis and p21 repression may also have an anticancer effect. For example, c-Myc and chemical p21 inhibitors, which repress p21, sensitize tumor cells to apoptosis by anticancer drugs. Further identification of factors that repress p21 is likely to contribute to the better understanding of its role in cancer.
TL;DR: Two recent studies used mouse genetics to assess the roles of PTEN and TSC2 in cancer, underscoring the importance of Akt-mTOR interplay for cancer progression and therapy.
TL;DR: This revision of Wilson and Cleary's model of health-related quality of life includes a taxonomy of the variables that often have been used to measure HRQoL and should be useful in research and clinical practice.
Abstract: Purpose: To revise the Wilson and Cleary model of health-related quality of life (HRQoL), with suggestions for applying each of the components, and to facilitate the use of HRQoL in nursing and health care.
Organizing Construct: HRQoL, based on relevant literature over the past 20 years.
Methods: The original model was revised in three substantive ways: (a) indicating that biological function is influenced by characteristics of both individuals and environments; (b) deleting nonmedical factors; and (c) deleting the labels on the arrows that tend to restrict characterization of the relationships.
Findings: Theoretical background is provided for each of the major components of the model, and examples of instruments to measure them, were added.
Conclusions: In quality-of-life research, the current challenge is to devise models to clarify the elements of health-related quality of life (HRQOL) and the causal relationships among them. This revision of Wilson and Cleary's model includes a taxonomy of the variables that often have been used to measure HRQoL. This revision should be useful in research and clinical practice.
TL;DR: The results suggest that CaMKII-dependent phosphorylation of RyR2 is involved in enhanced SR diastolic Ca leak and reduced SR Ca load in HF, and may thus contribute to arrhythmias and contractile dysfunction in HF.
Abstract: Abnormal release of Ca from sarcoplasmic reticulum (SR) via the cardiac ryanodine receptor (RyR2) may contribute to contractile dysfunction and arrhythmogenesis in heart failure (HF). We previously demonstrated decreased Ca transient amplitude and SR Ca load associated with increased Na/Ca exchanger expression and enhanced diastolic SR Ca leak in an arrhythmogenic rabbit model of nonischemic HF. Here we assessed expression and phosphorylation status of key Ca handling proteins and measured SR Ca leak in control and HF rabbit myocytes. With HF, expression of RyR2 and FK-506 binding protein 12.6 (FKBP12.6) were reduced, whereas inositol trisphosphate receptor (type 2) and Ca/calmodulin-dependent protein kinase II (CaMKII) expression were increased 50% to 100%. The RyR2 complex included more CaMKII (which was more activated) but less calmodulin, FKBP12.6, and phosphatases 1 and 2A. The RyR2 was more highly phosphorylated by both protein kinase A (PKA) and CaMKII. Total phospholamban phosphorylation was unaltered, although it was reduced at the PKA site and increased at the CaMKII site. SR Ca leak in intact HF myocytes (which is higher than in control) was reduced by inhibition of CaMKII but was unaltered by PKA inhibition. CaMKII inhibition also increased SR Ca content in HF myocytes. Our results suggest that CaMKII-dependent phosphorylation of RyR2 is involved in enhanced SR diastolic Ca leak and reduced SR Ca load in HF, and may thus contribute to arrhythmias and contractile dysfunction in HF.
TL;DR: Taken together, these relatively new and exciting data indicate that the future of nanomedicine is very promising, and that additional preclinical and clinical studies in relevant animal models and disease states, as well as long-term toxicity studies, should be conducted beyond the "proof-of-concept" stage.
TL;DR: Among healthy subjects with lesion-free baseline VCEs, celecoxib was associated with significantly fewer small bowel mucosal breaks than naproxen plus omeprazole, and should be considered in future trials with VCE.
TL;DR: This property provides a mechanism for the lack of desensitization, coincidence detection, and allodynia that characterize pain by allowing a sensory neuron to respond constantly to sustained stimulation that is suprathreshold and yet permitting the same cell to ignore sustained stimulating that is subthreshold (i.e., innocuous).
Abstract: Mechanosensory channels of sensory cells mediate the sensations of hearing, touch, and some forms of pain. The TRPA1 (a member of the TRP family of ion channel proteins) channel is activated by pain-producing chemicals, and its inhibition impairs hair cell mechanotransduction. As shown here and previously, TRPA1 is expressed by hair cells as well as by most nociceptors (small neurons of dorsal root, trigeminal, and nodose ganglia) and localizes to their sensory terminals (mechanosensory stereocilia and peripheral free nerves, respectively). Thus, TRPA1 channels are proposed to mediate transduction in both hair cells and nociceptors. Accordingly, we find that heterologously expressed TRPA1 display channel behaviors expected for both auditory and nociceptive transducers. First, TRPA1 and the hair cell transducer share a unique set of pore properties not described for any other channel (block by gadolinium, amiloride, gentamicin, and ruthenium red, a ranging conductance of approximately 100 pS that is reduced to 54% by calcium, permeating calcium-induced potentiation followed by closure, and reopening by depolarization), supporting a direct role of TRPA1 as a pore-forming subunit of the hair cell transducer. Second, TRPA1 channels inactivate in hyperpolarized cells but remain open in depolarized cells. This property provides a mechanism for the lack of desensitization, coincidence detection, and allodynia that characterize pain by allowing a sensory neuron to respond constantly to sustained stimulation that is suprathreshold (i.e., noxious) and yet permitting the same cell to ignore sustained stimulation that is subthreshold (i.e., innocuous). Our results support a TRPA1 role in both nociceptor and hair cell transduction.
TL;DR: This review summarizes the recent progress in the understanding of how the kinetics and energetics of membrane-protein interactions are regulated during the cellular membrane targeting and activation of peripheral proteins.
Abstract: ▪ Abstract Research in the past decade has revealed that many cytosolic proteins are recruited to different cellular membranes to form protein-protein and lipid-protein interactions during cell signaling and membrane trafficking. Membrane recruitment of these peripheral proteins is mediated by a growing number of modular membrane-targeting domains, including C1, C2, PH, FYVE, PX, ENTH, ANTH, BAR, FERM, and tubby domains, that recognize specific lipid molecules in the membranes. Structural studies of these membrane-targeting domains demonstrate how they specifically recognize their cognate lipid ligands. However, the mechanisms by which these domains and their host proteins are recruited to and interact with various cell membranes are only beginning to unravel with recent computational studies, in vitro membrane binding studies using model membranes, and cellular translocation studies using fluorescent protein-tagged proteins. This review summarizes the recent progress in our understanding of how the kinet...
TL;DR: Results supported the moral mandate hypothesis: Stronger moral conviction led to greater preferred social and physical distance from attitudinally dissimilar others, and a greater inability to generate procedural solutions to resolve disagreements.
Abstract: Attitudes held with strong moral conviction (moral mandates) were predicted to have different interpersonal consequences than strong but nonmoral attitudes. After controlling for indices of attitude strength, the authors explored the unique effect of moral conviction on the degree that people preferred greater social (Studies 1 and 2) and physical (Study 3) distance from attitudinally dissimilar others and the effects of moral conviction on group interaction and decision making in attitudinally homogeneous versus heterogeneous groups (Study 4). Results supported the moral mandate hypothesis: Stronger moral conviction led to (a) greater preferred social and physical distance from attitudinally dissimilar others, (b) intolerance of attitudinally dissimilar others in both intimate (e.g., friend) and distant relationships (e.g., owner of a store one frequents), (c) lower levels of good will and cooperativeness in attitudinally heterogeneous groups, and (d) a greater inability to generate procedural solutions to resolve disagreements.
TL;DR: This article investigated at the country level the effects of four cultural orientations identified and studied by Hofstede on two commonly recognized response biases: extreme response style and acquiescent responding, and found that individualism, uncertainty avoidance, power distance, and masculinity were each negatively associated with acquiescent response behavior.
Abstract: The authors investigated at the country level the effects of four cultural orientations identified and studied by Hofstede on two commonly recognized response biases: extreme response style and acquiescent responding. Data are presented from approximately 18,000 survey questionnaires completed by employees in 19 nations on five continents (Australia, Belgium, Brazil, Czech Republic, Germany, Hungary, India, Japan, Malaysia, Portugal, Turkey, the United Kingdom, Mexico, the Philippines, Poland, Singapore, Hong Kong, France, and Italy). Hierarchical linear modeling was employed to examine the associations between person-level response styles and country-level cultural orientations. Consistent with theoretical expectations, power distance and masculinity were found to be positively and independently associated with extreme response style. Individualism, uncertainty avoidance, power distance, and masculinity were each found to be negatively associated with acquiescent response behavior. Further research is ne...
10 May 2005
TL;DR: Experimental results using a large number of Web pages from diverse domains show that the proposed two-step technique is able to segment data records, align and extract data from them very accurately.
Abstract: This paper studies the problem of extracting data from a Web page that contains several structured data records. The objective is to segment these data records, extract data items/fields from them and put the data in a database table. This problem has been studied by several researchers. However, existing methods still have some serious limitations. The first class of methods is based on machine learning, which requires human labeling of many examples from each Web site that one is interested in extracting data from. The process is time consuming due to the large number of sites and pages on the Web. The second class of algorithms is based on automatic pattern discovery. These methods are either inaccurate or make many assumptions. This paper proposes a new method to perform the task automatically. It consists of two steps, (1) identifying individual data records in a page, and (2) aligning and extracting data items from the identified data records. For step 1, we propose a method based on visual information to segment data records, which is more accurate than existing methods. For step 2, we propose a novel partial alignment technique based on tree matching. Partial alignment means that we align only those data fields in a pair of data records that can be aligned (or matched) with certainty, and make no commitment on the rest of the data fields. This approach enables very accurate alignment of multiple data records. Experimental results using a large number of Web pages from diverse domains show that the proposed two-step technique is able to segment data records, align and extract data from them very accurately.
TL;DR: FoxM1 regulates transcription of cell cycle genes critical for progression into S-phase and mitosis, and is essential for transcription of the mitotic regulatory genes Cdc25B, Aurora B kinase, survivin, centromere protein A, and CENPB.
Abstract: The Forkhead box m1 (Foxm1) gene is critical for G(1)/S transition and essential for mitotic progression However, the transcriptional mechanisms downstream of FoxM1 that control these cell cycle events remain to be determined Here, we show that both early-passage Foxm1(-)(/)(-) mouse embryonic fibroblasts (MEFs) and human osteosarcoma U2OS cells depleted of FoxM1 protein by small interfering RNA fail to grow in culture due to a mitotic block and accumulate nuclear levels of cyclin-dependent kinase inhibitor (CDKI) proteins p21(Cip1) and p27(Kip1) Using quantitative chromatin immunoprecipitation and expression assays, we show that FoxM1 is essential for transcription of the mitotic regulatory genes Cdc25B, Aurora B kinase, survivin, centromere protein A (CENPA), and CENPB We also identify the mechanism by which FoxM1 deficiency causes elevated nuclear levels of the CDKI proteins p21(Cip1) and p27(Kip1) We provide evidence that FoxM1 is essential for transcription of Skp2 and Cks1, which are specificity subunits of the Skp1-Cullin 1-F-box (SCF) ubiquitin ligase complex that targets these CDKI proteins for degradation during the G(1)/S transition Moreover, early-passage Foxm1(-)(/)(-) MEFs display premature senescence as evidenced by high expression of the senescence-associated beta-galactosidase, p19(ARF), and p16(INK4A) proteins Taken together, these results demonstrate that FoxM1 regulates transcription of cell cycle genes critical for progression into S-phase and mitosis
TL;DR: An overview of studies leading to the identification of FoxO proteins as targets of insulin action and the mechanisms mediating the effects of insulin-like signaling on FoxO function is provided, emphasizing the role of Fox O proteins in mediatingThe effects ofulin on metabolism.
Abstract: There is increasing evidence that Forkhead box 'Other' (FoxO) proteins, a subgroup of the Forkhead transcription factor family, have an important role in mediating the effects of insulin and growth factors on diverse physiological functions, including cell proliferation, apoptosis and metabolism. Genetic studies in Caenorhabditis (Caenorhabditis elegans) and Drosophila demonstrate that FoxO proteins are ancient targets of insulin-like signaling involved in the regulation of metabolism and longevity. Studies in mammalian cells reveal that FoxO proteins regulate cell cycle progression and promote resistance to oxidative stress; both in vivo and cell culture studies support the concept that FoxO proteins have an important role in mediating the effects of insulin on metabolism, including its effects on hepatic glucose production. Phosphorylation and acetylation modulate FoxO function and control nuclear-cytoplasmic shuttling, DNA binding and protein-protein interactions. FoxO transcription factors exert positive and negative effects on gene expression, through direct binding to DNA target sites and protein-protein interactions with other transcription factors and coactivators. This paper provides an overview of studies leading to the identification of FoxO proteins as targets of insulin action and the mechanisms mediating the effects of insulin-like signaling on FoxO function, emphasizing the role of FoxO proteins in mediating the effects of insulin on metabolism.