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Selected AbstractsMechanistic links between climate and fisheries along the east coast of the United States: explaining population outbursts of Atlantic croaker (Micropogonias undulatus)FISHERIES OCEANOGRAPHY, Issue 1 2007JONATHAN A. HARE Abstract Climate has been linked to variation in marine fish abundance and distribution, but often the mechanistic processes are unknown. Atlantic croaker (Micropogonias undulatus) is a common species in estuarine and coastal areas of the mid-Atlantic and southeast coasts of the U.S. Previous studies have identified a correlation between Atlantic croaker abundance and winter temperatures in Chesapeake Bay, and have determined thermal tolerances of juveniles. Here we re-examine the hypothesis that winter temperature variability controls Atlantic croaker population dynamics. Abundance indices were analyzed at four life history stages from three regions along the east coast of the U.S. Correlations suggest that year-class strength is decoupled from larval supply and is determined by temperature-linked, overwinter survival of juveniles. Using a relation between air and water temperatures, estuarine water temperature was estimated from 1930 to 2002. Periods of high adult catch corresponded with warm winter water temperatures. Prior studies indicate that winter temperature along the east coast is related to the North Atlantic Oscillation (NAO); variability in catch is also correlated with the NAO, thereby demonstrating a link between Atlantic croaker dynamics, thermal limited overwinter survival, and the larger climate system of the North Atlantic. We hypothesize that the environment drives the large-scale variability in Atlantic croaker abundance and distribution, but fishing and habitat loss decrease the resiliency of the population to periods of poor environmental conditions and subsequent weak year classes. [source] Nitric oxide bioavailability modulates the dynamics of microvascular oxygen exchange during recovery from contractionsACTA PHYSIOLOGICA, Issue 2 2010D. M. Hirai Abstract Aim:, Lowered microvascular PO2 (PO2mv) during the exercise off-transient likely impairs muscle metabolic recovery and limits the capacity to perform repetitive tasks. The current investigation explored the impact of altered nitric oxide (NO) bioavailability on PO2mv during recovery from contractions in healthy skeletal muscle. We hypothesized that increased NO bioavailability (sodium nitroprusside: SNP) would enhance PO2mv and speed its recovery kinetics while decreased NO bioavailability (l -nitro arginine methyl ester: l -NAME) would reduce PO2mv and slow its recovery kinetics. Methods:,PO2mv was measured by phosphorescence quenching during transitions (rest,1 Hz twitch-contractions for 3 min,recovery) in the spinotrapezius muscle of Sprague,Dawley rats under SNP (300 ,m), Krebs-Henseleit (Control) and l -NAME (1.5 mm) superfusion conditions. Results:, Relative to recovery in Control, SNP resulted in greater overall microvascular oxygenation as assessed by the area under the PO2mv curve (PO2 AREA; Control: 3471 ± 292 mmHg s; SNP: 4307 ± 282 mmHg s; P < 0.05) and faster off-kinetics as evidenced by the mean response time (MRToff; Control: 60.2 ± 6.9 s; SNP: 34.8 ± 5.7 s; P < 0.05), whereas l -NAME produced lower PO2 AREA (2339 ± 444 mmHg s; P < 0.05) and slower MRToff (86.6 ± 14.5 s; P < 0.05). Conclusion:, NO bioavailability plays a key role in determining the matching of O2 delivery-to-O2 uptake and thus the upstream O2 pressure driving capillary-myocyte O2 flux (i.e. PO2mv) following cessation of contractions in healthy skeletal muscle. Additionally, these data support a mechanistic link between reduced NO bioavailability and prolonged muscle metabolic recovery commonly observed in ageing and diseased populations. [source] Nitric oxide and p53 in cancer-prone chronic inflammation and oxyradical overload disease,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2004Julie E. Goodman Abstract Nitric oxide (NO·), which is generated under chronic inflammatory conditions that predispose individuals to cancer, has paradoxical effects. NO· can activate p53, which can result in anti-carcinogenic effects, or it can be mutagenic and increase cancer risk. We explored the mechanisms by which NO· induced p53 activation in vitro and found that NO· induced p53 accumulation and phosphorylation, particularly at ser-15, via ATM and ATR kinases, which then led to cell cycle arrest at G2/M. We next examined proteins in these pathways in both inflamed and normal human colon tissue. Inducible nitric oxide synthase (iNOS) levels and p53-P-ser15 levels were positively correlated with the degree of inflammation and with each other. Additionally, the p53 targets, HDM-2 and p21 (WAF1), were present in ulcerative colitis (UC) colon, but undetectable in normal colon, consistent with activated p53. We also found higher p53 mutant frequencies of both G:C , A:T transitions at the CpG site of codon 248 and C:G , T:A transitions at codon 247 in lesional colon tissue from UC cases versus nonlesional tissue from these cases or colon tissue from normal adult controls. Consistent with nitrosative stress and the deamination of 5-methylcytosine, p53 mutations were also detected in sporadic colon cancer tissue and were associated with iNOS activity in these tissues. These studies identified a potential mechanistic link between NO· and p53 in UC and sporadic colon cancer. Environ. Mol. Mutagen. 44:3,9, 2004. Published 2004 Wiley-Liss, Inc. [source] Chlorophyll fluorescence as a bioindicator of effects on growth in aquatic macrophytes from mixtures of polycyclic aromatic hydrocarbonsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2001Christopher A. Marwood Abstract Chlorophyll- a fluorescence induction is a rapid technique for measuring photosynthetic electron transport in plants. To assess chlorophyll- a fluorescence as a bioindicator of effects of polycyclic aromatic hydrocarbon mixtures, chlorophyll- afluorescence parameters and plant growth responses to exposure to the wood preservative creosote were examined in the aquatic plants Lemna gibba and Myriophyllum spicatum. Exposure to creosote inhibited growth of L. gibba (EC50 = 7.2 mg/L total polycyclic aromatic hydrocarbons) and M. spicatum (EC50 = 2.6 mg/L) despite differences in physiology. Creosote also diminished maximum PSII efficiency (Fv/Fm) (EC50 = 36 and 13 mg/L for L. gibba and M. spicatum) and the effective yield of photosystem II photochemistry (,F/F,m) (EC50 = 13 and 15 mg/L for L. gibba and M. spicatum). The similarity between growth and chlorophyll- a fluorescence EC50s and slopes of the response curves suggests a close mechanistic link between these end points. The predictive power of chlorophyll- a fluorescence as a bioindicator of whole-organism effects applied to complex contaminant mixtures is discussed. [source] Breast cancer-derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: Implication for breast cancer osteolytic bone metastasesINTERNATIONAL JOURNAL OF CANCER, Issue 5 2008Guojun Bu Abstract Most breast cancer metastases in bone form osteolytic lesions, but the mechanisms of tumor-induced bone resorption and destruction are not fully understood. Although it is well recognized that Wnt/,-catenin signaling is important for breast cancer tumorigenesis, the role of this pathway in breast cancer bone metastasis is unclear. Dickkopf1 (Dkk1) is a secreted Wnt/,-catenin antagonist. In the present study, we demonstrated that activation of Wnt/,-catenin signaling enhanced Dkk1 expression in breast cancer cells and that Dkk1 overexpression is a frequent event in breast cancer. We also found that human breast cancer cell lines that preferentially form osteolytic bone metastases exhibited increased levels of Wnt/,-catenin signaling and Dkk1 expression. Moreover, we showed that breast cancer cell-produced Dkk1 blocked Wnt3A-induced osteoblastic differentiation and osteoprotegerin (OPG) expression of osteoblast precursor C2C12 cells and that these effects could be neutralized by a specific anti-Dkk1 antibody. In addition, we found that breast cancer cell conditioned media were able to block Wnt3A-induced NF-kappaB ligand reduction in C2C12 cells. Finally, we demonstrated that conditioned media from breast cancer cells in which Dkk1 expression had been silenced via RNAi were unable to block Wnt3A-induced C2C12 osteoblastic differentiation and OPG expression. Taken together, these results suggest that breast cancer-produced Dkk1 may be an important mechanistic link between primary breast tumors and secondary osteolytic bone metastases. © 2008 Wiley-Liss, Inc. [source] Metabolomics in the assessment of chemical-induced reproductive and developmental outcomes using non-invasive biological fluids: application to the study of butylbenzyl phthalateJOURNAL OF APPLIED TOXICOLOGY, Issue 8 2009Susan Sumner Abstract This study was conducted to evaluate the use of metabolomics for improving our ability to draw correlations between early life exposures and reproductive and/or developmental outcomes. Pregnant CD rats were exposed by gavage daily during gestation to vehicle or to butylbenzyl phthalate (BBP) in vehicle at a level known to induce effects in the offspring and at a level previously not shown to induce effects. Urine was collected for 24,h (on dry ice using all glass metabolism chambers) from dams on gestational day 18 (during exposure) and on post natal day (pnd) 21, and from pnd 25 pups. Traditional phenotypic anchors were measured in pups (between pnd 0 and pnd 26). Metabolomics of urine collected from dams exposed to vehicle or BBP exhibited different patterns for endogenous metabolites. Even three weeks after gestational exposure, metabolic profiles of endogenous compounds in urine could differentiate dams that received the vehicle, low dose or high dose of BBP. Metabolic profiles could differentiate male from female pups, pups born to dams receiving the vehicle, low or high BBP dose, and pups with observable adverse reproductive effects from pups with no observed effects. Metabolites significant to the separation of dose groups and their relationship with effects measured in the study were mapped to biochemical pathways for determining mechanistic relevance. The application of metabolomics to understanding the mechanistic link between low levels of environmental exposure and disease/dysfunction holds huge promise, because this technology is ideal for the analysis of biological fluids in human populations. Copyright © 2009 John Wiley & Sons, Ltd. [source] Cyclophilin D links programmed cell death and organismal aging in Podospora anserinaAGING CELL, Issue 5 2010Diana Brust Summary Cyclophilin D (CYPD) is a mitochondrial peptidyl prolyl- cis,trans -isomerase involved in opening of the mitochondrial permeability transition pore (mPTP). CYPD abundance increases during aging in mammalian tissues and in the aging model organism Podospora anserina. Here, we show that treatment of the P. anserina wild-type with low concentrations of the cyclophilin inhibitor cyclosporin A (CSA) extends lifespan. Transgenic strains overexpressing PaCypD are characterized by reduced stress tolerance, suffer from pronounced mitochondrial dysfunction and are characterized by accelerated aging and induction of cell death. Treatment with CSA leads to correction of mitochondrial function and lifespan to that of the wild-type. In contrast, PaCypD deletion strains are not affected by CSA within the investigated concentration range and show increased resistance against inducers of oxidative stress and cell death. Our data provide a mechanistic link between programmed cell death (PCD) and organismal aging and bear implications for the potential use of CSA to intervene into biologic aging. [source] Interleukin-1,: a bridge between inflammation and excitotoxicity?JOURNAL OF NEUROCHEMISTRY, Issue 1 2008Birgit Fogal Abstract Interleukin-1 (IL-1) is a proinflammatory cytokine released by many cell types that acts in both an autocrine and/or paracrine fashion. While IL-1 is best described as an important mediator of the peripheral immune response during infection and inflammation, increasing evidence implicates IL-1 signaling in the pathogenesis of several neurological disorders. The biochemical pathway(s) by which this cytokine contributes to brain injury remain(s) largely unidentified. Herein, we review the evidence that demonstrates the contribution of IL-1, to the pathogenesis of both acute and chronic neurological disorders. Further, we highlight data that leads us to propose IL-1, as the missing mechanistic link between a potential beneficial inflammatory response and detrimental glutamate excitotoxicity. [source] Transgenic mouse and cell culture models demonstrate a lack of mechanistic connection between endoplasmic reticulum stress and tau dysfunctionJOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2010M.L. Spatara Abstract In vivo aggregation of tau protein is a hallmark of many neurodegenerative disorders, including Alzheimer's disease (AD). Recent evidence has also demonstrated activation of the unfolded protein response (UPR), a cellular response to endoplasmic reticulum (ER) stress, in AD, although the role of the UPR in disease pathogenesis is not known. Here, three model systems were used to determine whether a direct mechanistic link could be demonstrated between tau aggregation and the UPR. The first model system used was SH-SY5Y cells, a neuronal cultured cell line that endogenously expresses tau. In this system, the UPR was activated using chemical stressors, tunicamycin and thapsigargin, but no changes in tau expression levels, solubility, or phosphorylation were observed. In the second model system, wild-type 4R tau and P301L tau, a variant with increased aggregation propensity, were heterologously overexpressed in HEK 293 cells. This overexpression did not activate the UPR. The last model system examined here was the PS19 transgenic mouse model. Although PS19 mice, which express the P301S variant of tau, display severe neurodegeneration and formation of tau aggregates, brain tissue samples did not show any activation of the UPR. Taken together, the results from these three model systems suggest that a direct mechanistic link does not exist between tau aggregation and the UPR. © 2010 Wiley-Liss, Inc. [source] Microbial exposure, interferon gamma gene demethylation in naïve T-cells, and the risk of allergic diseaseALLERGY, Issue 3 2009P. J. Vuillermin The period of immune programming during early life presents a critical window of opportunity for the prevention of allergic diseases. There is mounting evidence that inappropriate immune programming may involve disruption of specific epigenetic modifications (switches) at immune-related genes. This novel area of research has great potential, as epigenetic changes are known to be sensitive to environmental factors and may therefore provide a mechanistic link for the observed association between specific environmental cues, faulty immune development, and the risk of allergic disease. In addition, the dynamic and potentially reversible nature of epigenetic modifications offers potentially novel targets for therapeutic and/or preventative interventions. We review the evidence that (1) failure to up-regulate the interferon gamma (IFN,) response during infancy is an important determinant of the risk of allergic disease, (2) expression of the IFN, gene in naïve T-cells is regulated by epigenetic mechanisms, and (3) failure to up-regulate IFN, gene expression of naïve T-cells associated with low early life microbial exposure. Taken together, these lines of evidence suggest that low microbial exposure during early life increases the risk of allergic disease by reducing demethylation (activation) of the IFN, gene of naive T-cells. [source] Microarray analysis reveals that leptin induces autocrine/paracrine cascades to promote survival and proliferation of colon epithelial cells in an Apc genotype-dependent fashionMOLECULAR CARCINOGENESIS, Issue 1 2008Jenifer I. Fenton Abstract The imbalance in systemic mediators of inflammation, such as leptin, is thought to be involved in obesity-associated cancers. In addition, systemic endocrine signals can influence the local autocrine/paracrine factors produced within this microenvironment to influence epithelial cell fate. We previously demonstrated that leptin preferentially promotes the survival and proliferation of colon epithelial cells possessing an Apc mutation (IMCE) but not model normal cells (YAMC). Therefore, the purpose of this study was to identify leptin-induced functional gene family changes which characterize the response of colon epithelial cells possessing an Apc mutation but not normal cells. Consistent with our knowledge of colon carcinogenesis, genes regulating the Wnt/,-catenin-mediated pathway including Mdm2, Pik3r1, and Rb1 were upregulated by leptin. Importantly, leptin induced IGF-mediated pathway gene expression changes and their protein products in IMCE cells. In the IMCE cells IGFBP-6, IGF-1, and Crim1 expression was upregulated, while IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-5, and Nov expression was downregulated by leptin treatment. These data establish a biologically plausible mechanistic link between the elevated levels of growth factors and the increased risk of colon cancer associated with obesity. © 2007 Wiley-Liss, Inc. [source] NF-,B and cancer: Mechanisms and targetsMOLECULAR CARCINOGENESIS, Issue 6 2006Michael Karin Abstract In addition to being a central coordinator of immune responses, NF-,B signaling also plays a critical role in cancer development and progression and it may determine the response to therapy. NF-,B activation was shown to provide a critical mechanistic link between inflammation and cancer and is a major factor that controls the ability of both preneoplastic and malignant cells to resist apoptosis-based tumor surveillance mechanisms. NF-,B may also be involved in regulation of tumor angiogenesis and invasiveness. Importantly, NF-,B and the signaling pathways that mediate its activation have become attractive targets for development of new chemopreventive and chemotherapeutic approaches. © 2006 Wiley-Liss, Inc. [source] Review: Role of developmental inflammation and blood,brain barrier dysfunction in neurodevelopmental and neurodegenerative diseasesNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2009H. B. Stolp The causes of most neurological disorders are not fully understood. Inflammation and blood,brain barrier dysfunction appear to play major roles in the pathology of these diseases. Inflammatory insults that occur during brain development may have widespread effects later in life for a spectrum of neurological disorders. In this review, a new hypothesis suggesting a mechanistic link between inflammation and blood,brain barrier function (integrity), which is universally important in both neurodevelopmental and neurodegerative diseases, is proposed. The role of inflammation and the blood,brain barrier will be discussed in cerebral palsy, schizophrenia, Parkinson's disease, Alzheimer's disease and multiple sclerosis, conditions where both inflammation and blood,brain barrier dysfunction occur either during initiation and/or progression of the disease. We suggest that breakdown of normal blood,brain barrier function resulting in a short-lasting influx of blood-born molecules, in particular plasma proteins, may cause local damage, such as reduction of brain white matter observed in some newborn babies, but may also be the mechanism behind some neurodegenerative diseases related to underlying brain damage and long-term changes in barrier properties. [source] Fast foods, energy density and obesity: a possible mechanistic linkOBESITY REVIEWS, Issue 4 2003A. M. Prentice Summary Fast foods are frequently linked to the epidemic of obesity, but there has been very little scientific appraisal of a possible causal role. Here we review a series of studies demonstrating that the energy density of foods is a key determinant of energy intake. These studies show that humans have a weak innate ability to recognise foods with a high energy density and to appropriately down-regulate the bulk of food eaten in order to maintain energy balance. This induces so called ,passive over-consumption'. Composition data from leading fast food company websites are then used to illustrate that most fast foods have an extremely high energy density. At some typical outlets the average energy density of the entire menus is ,1100 kJ 100 g,1. This is 65% higher than the average British diet (,670 kJ 100 g,1) and more than twice the energy density of recommended healthy diets (,525 kJ 100 g,1). It is 145% higher than traditional African diets (,450 kJ 100 g,1) that probably represent the levels against which human weight regulatory mechanisms have evolved. We conclude that the high energy densities of many fast foods challenge human appetite control systems with conditions for which they were never designed. Among regular consumers they are likely to result in the accidental consumption of excess energy and hence to promote weight gain and obesity. [source] Loss of transgelin in repeated bouts of ulcerative colitis-induced colon carcinogenesisPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 4 2006Marie Yeo Abstract Though ulcerative colitis (UC)-associated colon cancer develops from dysplastic lesions caused by chronic inflammation, the specific mechanistic link between chronic inflammation and carcinogenesis in colon has not been integrated into molecular understanding. We therefore established an experimental animal model for colitic cancer, and used proteomic analysis, based on 2-DE and MALDI-TOF,MS, to identify proteins involved in colitic cancer. In our model, 6-week-old C57BL/6J mice were exposed to 15,cycles of dextran sodium sulfate (DSS), with each cycle consisting of 0.7% DSS for 1,week followed by distilled water for 10,days. Colorectal tumors developed in 22 of 24,mice (91.6%), with a tumor multiplicity of 1.727 per tumor-bearing mouse. Comparative 2-DE analysis showed that 38,protein spots were differentially expressed in colon tumors and normal colon. We identified 27 of these proteins, including GRP94, HSC70, enolase, prohibitin, and transgelin. The reduction of transgelin expression in mouse colon tumors was confirmed by Western blotting and immunohistochemistry. We also found that transgelin expression was significantly reduced in human colon tumors compared with adjacent nontumorous tissues. In conclusion, these results suggest that loss of transgelin could be a candidate for biomarker of repeated colitis-associated colon cancer. [source] Early mouse embryo development: could epigenetics influence cell fate determination?BIOESSAYS, Issue 6 2007Amandine Henckel It is generally assumed that the developmental program of embryogenesis relies on epigenetic mechanisms. However, a mechanistic link between epigenetic marks and cell fate decisions had not been established so far. In a recent article, Torres-Padilla and colleagues1 show that epigenetic information and, more precisely, histone arginine methylation mediated by CARM1 could contribute to cell fate decisions in the mouse 4-cell-stage embryo. It provides the first indications that global epigenetic information influences allocation of pluripotent cells toward the first cell lineages. BioEssays 29:520,524, 2007. © 2007 Wiley Periodicals, Inc. [source] Effects of hydrogen peroxide and apolipoprotein E isoforms on apolipoprotein E trafficking in HepG2 cellsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2009Tharani Sabaretnam Summary 1.,The major source of apolipoprotein E (apoE) is the liver. In the present study, the effects of oxidative stress and apoE isoforms on apoE distribution and trafficking were established using the HepG2 liver tumour cell line. 2.,Hydrogen peroxide (0, 25, 250 and 1000 ,mol/L) was associated with rapid and concentration-dependent redistribution of apoE into the early endosomal compartment. This redistribution was achieved with a much lower concentration (25 ,mol/L) than that needed to induce changes in intracellular apoE mRNA expression, apoE protein levels and markers of oxidative stress (250,1000 ,mol/L). 3.,Live cell imaging of apoE3,green fluorescent protein revealed a significant decrease in traffic velocity in response to oxidative stress. 4.,The E4 isoform was associated with reduced trafficking velocity compared with the E3 isoform under basal conditions. 5.,The results indicate that oxidative stress and apoE isoforms influence apoE trafficking and distribution within HepG2 cells. Altered apoE hepatocyte trafficking may provide a mechanistic link between oxidative stress, ageing and some diseases in older people. [source] The role of intramuscular lipid in insulin resistanceACTA PHYSIOLOGICA, Issue 4 2003B. D. Hegarty Abstract There is interest in how altered lipid metabolism could contribute to muscle insulin resistance. Many animal and human states of insulin resistance have increased muscle triglyceride content, and there are now plausible mechanistic links between muscle lipid accumulation and insulin resistance, which go beyond the classic glucose,fatty acid cycle. We postulate that muscle cytosolic accumulation of the metabolically active long-chain fatty acyl CoAs (LCACoA) is involved, leading to insulin resistance and impaired insulin signalling or impaired enzyme activity (e.g. glycogen synthase or hexokinase) either directly or via chronic translocation/activation of mediators such as a protein kinase C (particularly PKC , and ,). Ceramides and diacylglycerols (DAGs) have also been implicated in forms of lipid-induced muscle insulin resistance. Dietary lipid-induced muscle insulin resistance in rodents is relatively easily reversed by manipulations that lessen cytosolic lipid accumulation (e.g. diet change, exercise or fasting). PPAR agonists (both , and ,) also lower muscle LCACoA and enhance insulin sensitivity. Activation of AMP-activated protein kinase (AMPK) by AICAR leads to muscle enhancement (especially glycolytic muscle) of insulin sensitivity, but involvement of altered lipid metabolism is less clear cut. In rodents there are similarities in the pattern of muscle lipid accumulation/PKC translocation/altered insulin signalling/insulin resistance inducible by 3,5-h acute free fatty acid elevation, 1,4 days intravenous glucose infusion or several weeks of high-fat feeding. Recent studies extend findings and show relevance to humans. Muscle cytosolic lipids may accumulate either by increased fatty acid flux into muscle, or by reduced fatty acid oxidation. In some circumstances muscle insulin resistance may be an adaptation to optimize use of fatty acids when they are the predominant available energy fuel. The interactions described here are fundamental to optimizing therapy of insulin resistance based on alterations in muscle lipid metabolism. [source] Cancer risk among patients hospitalized for Type 1 diabetes mellitus: a population-based cohort study in SwedenDIABETIC MEDICINE, Issue 7 2010X. Shu Diabet. Med. 27, 791,797 (2010) Abstract Aims, Type 1 diabetes mellitus (T1DM) is an autoimmune disease with potential mechanistic links to immune-related cancers. We aimed at examining the overall and specific cancer risks among hospitalized T1DM patients from the national registers in Sweden. Methods, A T1DM research cohort was created by identifying T1DM patients from the Hospital Discharge Register and linking them with the Cancer Registry. Standardized incidence ratios (SIRs) for subsequent cancers were calculated among patients with T1DM compared with those without T1DM. Results, Two hundred and fifty-eight cases were ascertained with subsequent cancers during the follow-up duration from 1964 to 2006, with an increased overall SIR of 1.17 (95% CI 1.04,1.33) among 24 052 T1DM patients identified at baseline. Significant excess was noted for gastric and skin (squamous cell carcinoma) cancers and for leukaemia. Increased risk of acute lymphatic leukaemia accounted for most of the variation of leukaemia risk (SIR = 5.31, 95% CI 3.32,8.05). Cancer risk varied with sex, age at first hospitalization and numbers of hospitalizations. The risk was higher in women compared with men and in those hospitalized for T1DM at age over 10 years compared with the younger patients. Higher risks were also found among those with more hospital visits. Conclusion, By quantifying the variations of overall and site-specific cancer risks after T1DM, the current study provides novel associations between T1DM and subsequent cancers, the mechanisms of which remain to be established. [source] Increased susceptibility to oxidative stress as a proximate cost of reproductionECOLOGY LETTERS, Issue 5 2004Carlos Alonso-Alvarez Abstract In iteroparous species high investment in current reproduction is usually paid in terms of reduced future reproduction and increased mortality. However, the proximal mechanisms of these costs remain poorly understood. Free radicals arising as by-products of normal metabolic activities have deleterious effects on cellular proteins, lipids and DNA, and this phenomenon is known as oxidative stress. Since reproduction is an energetically demanding activity, which increases both basal and field metabolic rates, one could expect that breeding effort generates an oxidative stress whose strength depends on the availability and efficiency of antioxidant defences. In agreement with this prediction, we show here for the first time that reproduction decreases antioxidant defences, illustrating that oxidative stress represents a cost of reproduction. We suggest that increased susceptibility to oxidative stress might be a general proximal connection between reproduction and survival underlying other mechanistic links previously acknowledged. [source] Cell resilience in species life spans: a link to inflammation?AGING CELL, Issue 4 2010Caleb E. Finch Summary Species differences in life span have been attributed to cellular survival during various stressors, designated here as ,cell resilience'. In primary fibroblast cultures, cell resilience during exposure to free radicals, hypoglycemia, hyperthermia, and various toxins has shown generally consistent correlations with the species characteristic life spans of birds and mammals. However, the mechanistic links of cell resilience in fibroblast cultures to different species life spans are poorly understood. We propose that certain experimental stressors are relevant to somatic damage in vivo during inflammatory responses of innate immunity, particularly, resistance to reactive oxygen species (ROS), low glucose, and hyperthermia. According to this hypothesis, somatic cell resilience determines species differences in longevity during repeated infections and traumatic injuries in the natural environment. Infections and injury expose local fibroblasts and other cells to ROS generated by macrophages and to local temperature elevations. Systemically, acute phase immune reactions cause hypoglycemia and hyperthermia. We propose that cell resilience to somatic stressors incurred in inflammation is important in the evolution of longevity and that longer-lived species are specifically more resistant to immune-related stressors. This hypothesis further specifies Kirkwood's disposable soma theory. We suggest expanding the battery of stressors and markers used for comparative studies to additional cell types and additional parameters relevant to host defense and to their ecological specificities. [source] Behavioral intermittence, Lévy patterns, and randomness in animal movementOIKOS, Issue 4 2009F. Bartumeus The recent debate on both the existence and the cause of fractal (Lévy) patterns in animal movement resonates with much deeper and richer problems in movement ecology: (1) establishing mechanistic links between animal behavior and statistical patterns of movement, and (2) understanding what is the role of randomness (stochasticity) in animal motion. Here, the idea of behavioral intermittence is shown to be crucial to establish mechanistic connections between the behavior of organisms and the statistical properties they generate when moving. Attention is drawn to the fact that some random walk modeling procedures can impair the identification of intermittent biological mechanisms which could govern major statistical properties of movement. This fact, together with some misconceptions and prejudices regarding the role of randomness in animal motion may explain why stochastic processes have been disregarded as a potential source of adaptation in animal movement. In the near future, the advances in biotelemetry together with a more explicit consideration of behavioral intermittence, and the development of novel random walk approaches, could help us to set up the bases for a landscape-level behavioral ecology. [source] | |||||||||||||||||||||||||