205 research outputs found
Age Differences In Emotional Response To Future Events
Much prior research has been conducted on how emotions change across the life span. The current study aimed to determine age differences in emotional responses to future events by utilizing Linguistic Inquiry Word Count (LIWC) software to determine the quantitative usage of anxiety related words by both younger and older adults when speaking about common future events. All participants (n= 107) were asked to share three neutral past events and three neutral possible future events. These narratives were analyzed via LIWC. Prior research shows that younger adults tend to experience more worry about the future than older adults. According to the socioemotional selectivity theory, positive and negative processing biases are a product of time perspective. Furthermore, the discrete emotions theory of aging predicts that older adults experience an increase in sadness due to uncontrollable losses. Individual correlations of anxiety related words use for past and future events were not statistically significant. However, follow-up t-tests on anxiety related word usage in young, middle-aged, and older adults, found that younger adults used more anxiety related words when speaking about the future as compared to older adults. Older adults, however, used more anxiety related words when speaking about the past than middle-aged adults.
Deficiency of the BMP Type I receptor ALK3 partly protects mice from anemia of inflammation
Background: Inflammatory stimuli induce the hepatic iron regulatory hormone hepcidin, which contributes to anaemia of inflammation (AI). Hepcidin expression is regulated by the bone morphogenetic protein (BMP) and the interleukin-6 (IL-6) signalling pathways. Prior results indicate that the BMP type I receptor ALK3 is mainly involved in the acute inflammatory hepcidin induction four and 72Â h after IL-6 administration. In this study, the role of ALK3 in a chronic model of inflammation was investigated. The intact, heat-killed bacterium Brucella abortus (BA) was used to analyse its effect on the development of inflammation and hypoferremia in mice with hepatocyte-specific Alk3-deficiency (Alk3fl/fl; Alb-Cre) compared to control (Alk3fl/fl) mice.
Results: An iron restricted diet prevented development of the iron overload phenotype in mice with hepatocyte-specific Alk3 deficiency. Regular diet leads to iron overload and increased haemoglobin levels in these mice, which protects from the development of AI per se. Fourteen days after BA injection Alk3fl/fl; Alb-Cre mice presented milder anaemia (Hb 16.7Â g/dl to 11.6Â g/dl) compared to Alk3fl/fl control mice (Hb 14.9Â g/dl to 8.6Â g/dl). BA injection led to an intact inflammatory response in all groups of mice. In Alk3fl/fl; Alb-Cre mice, SMAD1/5/8 phosphorylation was reduced after BA as well as after infection with Staphylococcus aureus. The reduction of the SMAD1/5/8 signalling pathway due to hepatocyte-specific Alk3 deficiency partly suppressed the induction of STAT3 signalling.
Conclusion: The results reveal in vivo, that 1) hepatocyte-specific Alk3 deficiency partly protects from AI, 2) the development of hypoferremia is partly dependent on ALK3, and 3) the ALK3/BMP/hepcidin axis may serve as a possible therapeutic target to attenuate AI
Elevated Hepcidin Is Part of a Complex Relation That Links Mortality with Iron Homeostasis and Anemia in Men and Women with HIV Infection.
BACKGROUND: Early and chronic inflammation is a hallmark of HIV infection, and inflammation is known to increase hepcidin expression. Consequently, hepcidin may be a key determinant of the iron homeostasis and anemia associated with poorer HIV prognoses. OBJECTIVE: The objective of this study was to understand how hepcidin is related to anemia, iron homeostasis, and inflammation at HIV diagnosis and to investigate associations between hepcidin and all-cause mortality in HIV infection. METHODS: In a retrospective cohort, baseline plasma hepcidin was measured by competitive enzyme immunoassay within 3 mo of HIV diagnosis in 196 antiretroviral-naive Gambians. Iron homeostasis [hemoglobin, plasma transferrin, ferritin, iron, soluble transferrin receptor (sTfR)] and inflammation [α1-antichymotrypsin (ACT)] from the same plasma sample were available, as were absolute CD4 cell counts, age, gender, body mass index (BMI), and HIV type. RESULTS: Anemia was common across the spectrum of immunosuppression [CD4 cell counts (prevalence of anemia): >500 cells/μL (68%), 200-500 cells/μL (73%), and <200 cells/μL (89%); P = 0.032] and in men (81%) and women (76%). Increasing hepcidin was associated with iron homeostasis biomarkers (higher ferritin and lower transferrin, hemoglobin, and sTfR), inflammation (higher ACT), and key health indicators (lower CD4 or BMI, advancing age, and male gender; P < 0.001 except for hemoglobin, P = 0.021). Elevated hepcidin was associated with greater all-cause mortality in a dose-dependent manner [intermediate vs. lowest tertile: unadjusted HR (95% CI), 1.95 (1.22, 3.10); upper vs. lowest tertile: 3.02 (1.91, 4.78)]. Principal components analysis identified 2 patterns composed of hepcidin-ferritin-transferrin, with or without ACT, and iron-sTfR-hemoglobin that may distinguish inflammation and erythropoiesis iron functions. CONCLUSIONS: Elevated hepcidin is independently associated with greater mortality in men and women with HIV infection, and hepcidin is also part of a complex relation linking iron homeostasis, anemia, and HIV. Understanding the mechanisms and role of hepcidin modulation may further guide evidence-based interventions needed to counter detrimental iron homeostasis and anemia in HIV infection
Redox cycling metals: Pedaling their roles in metabolism and their use in the development of novel therapeutics
Essential metals, such as iron and copper, play a critical role in a plethora of cellular processes including cell growth and proliferation. However, concomitantly, excess of these metal ions in the body can have deleterious effects due to their ability to generate cytotoxic reactive oxygen species (ROS). Thus, the human body has evolved a very well-orchestrated metabolic system that keeps tight control on the levels of these metal ions. Considering their very high proliferation rate, cancer cells require a high abundance of these metals compared to their normal counterparts. Interestingly, new anti-cancer agents that take advantage of the sensitivity of cancer cells to metal sequestration and their susceptibility to ROS have been developed. These ligands can avidly bind metal ions to form redox active metal complexes, which lead to generation of cytotoxic ROS. Furthermore, these agents also act as potent metastasis suppressors due to their ability to up-regulate the metastasis suppressor gene, N-myc downstream regulated gene 1. This review discusses the importance of iron and copper in the metabolism and progression of cancer, how they can be exploited to target tumors and the clinical translation of novel anti-cancer chemotherapeutics
Tilt-Up Building Seismic Design - Precast or Cast-in Place?
Tilt-up buildings have been successfully designed and constructed throughout the United States for over fifty years. Today, the tiltup method of construction is used extensively to build all types of buildings, currently at a rate of 300,000,000 square feet of tilt-up concrete panels constructed in the United States each year. Recently, with the adoption of the 2006 edition of the International Building Code (IBC) in conjunction with the ASCE 7-05 Minimum Design Loads for Buildings and Other Structures , there has developed some confusion over what building type should tilt-up construction be classified for the purposes of seismic design – monolithic cast-in-place or precast
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