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Sample records for included alterations leading

  1. Lead acid batteries simulation including experimental validation

    Energy Technology Data Exchange (ETDEWEB)

    Achaibou, N.; Malek, A. [Division Energie Solaire Photovoltaique, Centre de Developpement des Energies Renouvelables, B.P. 62, Route de l' Observatoire, Bouzareah, Alger (Algeria); Haddadi, M. [Laboratoire de Dispositif de Communication et de Conversion Photovoltaique Ecole Nationale Polytechnique, Rue Hassen Badi, El Harrach, Alger (Algeria)

    2008-12-01

    The storage of energy in batteries is a cause of the failure and loss of reliability in PV systems. The battery behavior has been largely described in the literature by many authors; the selected models are of Monegon and CIEMAT. This paper reviews the two general lead acid battery models and their agreement with experimental data. In order to validate these models, the behavior of different battery cycling currents has been simulated. Results obtained have been compared to real data. The CIEMAT model presents a good performance compared to Monegon's model. (author)

  2. Histological and histochemical alterations in the kidney induced by lead

    International Nuclear Information System (INIS)

    Jarrar, Bashir M.

    2003-01-01

    Although lead intoxication is one of the most common forms of metal intoxication,the histochemichal alterations in renal tissues due to chronic lead exposure is limited and has not yet been well identified. A total of 60 male Wistar albino rats were exposed to lead acetate trihydrate( 0.0, 0.25, 0.5, 1.0 and 2% for 1 to 12 months) in drinking water to investigate the histological and histochemical alterations in renal tissues due to lead. Chronic exposure to the subtoxic doses of lead produced distinct progressive tubular, glomerular and interstitial damages. Tubular changes occured earlier than the glomerular and interstitial ones,and included anisokaryosis, nuclear pyknosis,karyomeglay, development of intranuclear cytoplasmic inclusions together with tubular dilation, necrosis,vacuolization, tubular hyperplasia and solid tubular adenoma. The glomrular alterations were mainly mesangial hypercellularity, segmental glomerulosclerosis, glomerular hyalinization and glomerular tuft alterations. The findings indicate that lead produces significant histological and histochemical changes in the kidney that lead to severe complications. (author)

  3. Natural alteration products of sulphide mattes from primary lead smelting

    Czech Academy of Sciences Publication Activity Database

    Ettler, V.; Johan, Z.; Hradil, David

    2003-01-01

    Roč. 335, č. 14 (2003), s. 1013-1020 ISSN 1631-0713 R&D Projects: GA MŠk LN00A028; GA ČR GP205/01/D132 Institutional research plan: CEZ:AV0Z4032918 Keywords : matte * lead smelting * alteration Subject RIV: CA - Inorganic Chemistry Impact factor: 0.366, year: 2003

  4. Arsenic and Manganese Alter Lead Deposition in the Rat

    Science.gov (United States)

    Andrade, V; Mateus, ML; Santos, D; Aschner, M; Batoreu, MC; Marreilha dos Santos, AP

    2014-01-01

    Lead (Pb) continues to be a major toxic metal in the environment. Pb exposure frequently occurs in the presence of other metals, such as arsenic (As) and manganese (Mn). Continued exposure to low levels of these metals may lead to long-term toxic effects due to their accumulation in several organs. Despite the recognition that metals in a mixture may alter each other’s toxicity by affecting deposition, there is dearth of information on their interactions in vivo. In this work, we investigated the effect of As and Mn on Pb tissue deposition, focusing on the kidney, brain and liver. Wistar rats were treated with 8 doses of each single metal, Pb (5 mg/Kg bw), As (60 mg/L) and Mn mg/Kg bw), or the same doses in a triple metal mixture. Kidney, brain, liver, blood and urine Pb, As and Mn concentrations were determined by graphite furnace atomic absorption spectrophotometry. Pb kidney, brain and liver concentrations in the metal mixture-treated group were significantly increased compared to the Pb alone treated group, being more pronounced in the kidney (5.4 fold), brain (2.5 fold) and liver (1.6 fold). Urinary excretion of Pb in the metal mixture-treated rats significantly increased compared with the Pb treated group, although blood Pb concentrations were analogous to the Pb treated group. Co-treatment with As, Mn and Pb alters Pb deposition compared to Pb alone treatment, increasing Pb accumulation predominantly in kidney and brain. Blood Pb levels, unlike urine, do not reflect the increased Pb deposition in the kidney and brain. Taken together, the results suggest that the nephro- and neurotoxicity of “real-life” Pb exposure scenarios should be considered within the context of metal mixture exposures. PMID:24715659

  5. Chronic social stress leads to altered sleep homeostasis in mice.

    Science.gov (United States)

    Olini, Nadja; Rothfuchs, Iru; Azzinnari, Damiano; Pryce, Christopher R; Kurth, Salome; Huber, Reto

    2017-06-01

    Disturbed sleep and altered sleep homeostasis are core features of many psychiatric disorders such as depression. Chronic uncontrollable stress is considered an important factor in the development of depression, but little is known on how chronic stress affects sleep regulation and sleep homeostasis. We therefore examined the effects of chronic social stress (CSS) on sleep regulation in mice. Adult male C57BL/6 mice were implanted for electrocortical recordings (ECoG) and underwent either a 10-day CSS protocol or control handling (CON). Subsequently, ECoG was assessed across a 24-h post-stress baseline, followed by a 4-h sleep deprivation, and then a 20-h recovery period. After sleep deprivation, CSS mice showed a blunted increase in sleep pressure compared to CON mice, as measured using slow wave activity (SWA, electroencephalographic power between 1-4Hz) during non-rapid eye movement (NREM) sleep. Vigilance states did not differ between CSS and CON mice during post-stress baseline, sleep deprivation or recovery, with the exception of CSS mice exhibiting increased REM sleep during recovery sleep. Behavior during sleep deprivation was not affected by CSS. Our data provide evidence that CSS alters the homeostatic regulation of sleep SWA in mice. In contrast to acute social stress, which results in a faster SWA build-up, CSS decelerates the homeostatic build up. These findings are discussed in relation to the causal contribution of stress-induced sleep disturbance to depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Environmental disruption of the circadian clock leads to altered sleep and immune responses in mouse.

    Science.gov (United States)

    Phillips, Derrick J; Savenkova, Marina I; Karatsoreos, Ilia N

    2015-07-01

    In mammals, one of the most salient outputs of the circadian (daily) clock is the timing of the sleep-wake cycle. Modern industrialized society has led to a fundamental breakdown in the relationship between our endogenous timekeeping systems and the solar day, disrupting normal circadian rhythms. We have argued that disrupted circadian rhythms could lead to changes in allostatic load, and the capacity of organisms to respond to other environmental challenges. In this set of studies, we apply a model of circadian disruption characterized in our lab in which mice are housed in a 20h long day, with 10h of light and 10h of darkness. We explored the effects of this environmental disruption on sleep patterns, to establish if this model results in marked sleep deprivation. Given the interaction between circadian, sleep, and immune systems, we further probed if our model of circadian disruption also alters the innate immune response to peripheral bacterial endotoxin challenge. Our results demonstrate that this model of circadian disruption does not lead to marked sleep deprivation, but instead affects the timing and quality of sleep. We also show that while circadian disruption does not lead to basal changes in the immune markers we explored, the immune response is affected, both in the brain and the periphery. Together, our findings further strengthen the important role of the circadian timing system in sleep regulation and immune responses, and provide evidence that disrupting the circadian clock increases vulnerability to further environmental stressors, including immunological challenges. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Circadian Clock Protein Content and Daily Rhythm of Locomotor Activity Are Altered after Chronic Exposure to Lead in Rat

    Directory of Open Access Journals (Sweden)

    Mariam Sabbar

    2017-09-01

    Full Text Available Lead exposure has been reported to produce many clinical features, including parkinsonism. However, its consequences on the circadian rhythms are still unknown. Here we aimed to examine the circadian rhythms of locomotor activity following lead intoxication and investigate the mechanisms by which lead may induce alterations of circadian rhythms in rats. Male Wistar rats were injected with lead or sodium acetate (10 mg/kg/day, i.p. during 4 weeks. Both groups were tested in the “open field” to quantify the exploratory activity and in the rotarod to evaluate motor coordination. Then, animals were submitted to continuous 24 h recordings of locomotor activity under 14/10 Light/dark (14/10 LD cycle and in complete darkness (DD. At the end of experiments, the clock proteins BMAL1, PER1-2, and CRY1-2 were assayed in the suprachiasmatic nucleus (SCN using immunohistochemistry. We showed that lead significantly reduced the number of crossing in the open field, impaired motor coordination and altered the daily locomotor activity rhythm. When the LD cycle was advanced by 6 h, both groups adjusted their daily locomotor activity to the new LD cycle with high onset variability in lead-intoxicated rats compared to controls. Lead also led to a decrease in the number of immunoreactive cells (ir- of BMAL1, PER1, and PER2 without affecting the number of ir-CRY1 and ir-CRY2 cells in the SCN. Our data provide strong evidence that lead intoxication disturbs the rhythm of locomotor activity and alters clock proteins expression in the SCN. They contribute to the understanding of the mechanism by which lead induce circadian rhythms disturbances.

  8. Lead intoxication in gestational and lactation periods alters the development of male reproductive organs.

    Science.gov (United States)

    Corpas, Isabel; Castillo, M; Marquina, Domingo; Benito, Maria J

    2002-10-01

    The effect of lead (Pb) intoxication during pregnancy and lactation on the male reproductive system was studied to evaluate the alterations caused by Pb in the development of pups. The investigations covered the effect of lead on the course of spermatogenesis and the development of the epididymis and reproductive glands. For this purpose, dams were intoxicated with 300 mg/L Pb during the gestational period and through lactation. Pups were sacrificed on Postnatal (PN) Days 12 and 21. Blood lead (PbB) and plasma iron concentrations were measured, and blood cells counted. Biochemical studies as well as histochemical analyses were performed on testes and accessory glands of the reproductive system. Lead intoxication resulted in a decrease in testis and seminal vesicle weights and an increase in DNA and RNA levels on PN Day 21. Total protein was significantly decreased by the toxicant, and alkaline and acid phosphatase levels of the gonads were reduced. Effects were also reflected in the reduction of the thickness of epithelium and of seminiferous tubule diameter (STD) as a consequence of the action of lead in the reduction in numbers of prospermatogonia and spermatocytes. Results indicate that the reproductive system targets of lead intoxication are not only the testes; lead intoxication results in the inhibition of testicular, epididymal, and seminal vesicle function, altering the biochemical composition of these organs, and consequently, affecting the normal development of germinal cells.

  9. Influence of Melting and Hydrothermal Alteration on Lead in Abyssal Peridotites

    Science.gov (United States)

    Warren, J. M.; D'Errico, M. E.; Godard, M.; Coble, M. A.; Horan, M.

    2017-12-01

    The lead isotopic system is a key tracer of mantle convection, yet the abundance and mineralogical hosts of Pb in the upper mantle are poorly constrained. To address this, we analyzed the concentration of Pb in minerals and bulk rock powders of abyssal peridotites. These samples represent the oceanic upper mantle following melt extraction. They can be used to explore the mantle Pb budget, assuming that the amount of Pb lost during mantle melting and gained during seafloor alteration can be determined. We performed in situ analysis of the three main silicate phases (olivine, orthopyroxene, and clinopyroxene), which yield Pb concentrations of 2-30 ppb. Olivine is the main mineralogical host of Pb, unlike other trace elements, which are predominantly hosted in clinopyroxene. Sulfide contains an average of 3 ppm Pb, but these high concentrations are offset by low modal abundances (100 ppb [1, 2], measured by inductively-coupled plasma mass spectrometry. The higher values among literature data may reflect a combination of lower analytical sensitivity and effects of alteration. Samples in this study include an unaltered peridotite from the Gakkel Ridge, which shows the closest agreement between reconstructed and measured whole rock values. We estimate that our peridotites have undergone 5 to 9% melting [3], based on non-modal fractional melt modeling of rare earth element abundances. Assuming 18 to 23 ppb Pb in the depleted source mantle [4, 5], expected concentrations in abyssal peridotites after melting are Pet.; [2] Paulick et al., 2006, Chem. Geol.; [3] D'Errico et al., 2016, GCA; [4] Salters and Stracke, 2004, G-Cubed; [5] Workman and Hart, 2005 EPSL.

  10. Cooling Strategies for Vane Leading Edges in a Syngas Environment Including Effects of Deposition and Turbulence

    Energy Technology Data Exchange (ETDEWEB)

    Ames, Forrest [Univ. of North Dakota, Grand Forks, ND (United States); Bons, Jeffrey [Univ. of North Dakota, Grand Forks, ND (United States)

    2014-09-30

    The Department of Energy has goals to move land based gas turbine systems to alternate fuels including coal derived synthetic gas and hydrogen. Coal is the most abundant energy resource in the US and in the world and it is economically advantageous to develop power systems which can use coal. Integrated gasification combined cycles are (IGCC) expected to allow the clean use of coal derived fuels while improving the ability to capture and sequester carbon dioxide. These cycles will need to maintain or increase turbine entry temperatures to develop competitive efficiencies. The use of coal derived syngas introduces a range of potential contaminants into the hot section of the gas turbine including sulfur, iron, calcium, and various alkali metals. Depending on the effectiveness of the gas clean up processes, there exists significant likelihood that the remaining materials will become molten in the combustion process and potentially deposit on downstream turbine surfaces. Past evidence suggests that deposition will be a strong function of increasing temperature. Currently, even with the best gas cleanup processes a small level of particulate matter in the syngas is expected. Consequently, particulate deposition is expected to be an important consideration in the design of turbine components. The leading edge region of first stage vanes most often have higher deposition rates than other areas due to strong fluid acceleration and streamline curvature in the vicinity of the surface. This region remains one of the most difficult areas in a turbine nozzle to cool due to high inlet temperatures and only a small pressure ratio for cooling. The leading edge of a vane often has relatively high heat transfer coefficients and is often cooled using showerhead film cooling arrays. The throat of the first stage nozzle is another area where deposition potentially has a strongly adverse effect on turbine performance as this region meters the turbine inlet flow. Based on roughness

  11. Altered lipid homeostasis in Drosophila InsP3 receptor mutants leads to obesity and hyperphagia

    Directory of Open Access Journals (Sweden)

    Manivannan Subramanian

    2013-05-01

    Obesity is a complex metabolic disorder that often manifests with a strong genetic component in humans. However, the genetic basis for obesity and the accompanying metabolic syndrome is poorly defined. At a metabolic level, obesity arises from an imbalance between the nutritional intake and energy utilization of an organism. Mechanisms that sense the metabolic state of the individual and convey this information to satiety centers help achieve this balance. Mutations in genes that alter or modify such signaling mechanisms are likely to lead to either obese individuals, who in mammals are at high risk for diabetes and cardiovascular disease, or excessively thin individuals with accompanying health problems. Here we show that Drosophila mutants for an intracellular calcium signaling channel, the inositol 1,4,5-trisphosphate receptor (InsP3R store excess triglycerides in their fat bodies and become unnaturally obese on a normal diet. Although excess insulin signaling can rescue obesity in InsP3R mutants to some extent, we show that it is not the only cause of the defect. Through mass spectrometric analysis of lipids we find that homeostasis of storage and membrane lipids are altered in InsP3R mutants. Possibly as a compensatory mechanism, InsP3R mutant adults also feed excessively. Thus, reduced InsP3R function alters lipid metabolism and causes hyperphagia in adults. Together, the metabolic and behavioral changes lead to obesity. Our results implicate altered InsP3 signaling as a previously unknown causative factor for metabolic syndrome in humans. Importantly, our studies also suggest preventive dietary interventions.

  12. Haemato-biochemical alterations induced by lead acetate toxicity in wistar rats

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    S. G. Suradkar

    Full Text Available An experiment was conducted to study the haemato-biochemical alterations induced by lead acetate toxicity in 48 Wistar rats of either sex, divided uniformly into four different groups. The rats of group I received only deionised water as control while, group II, III and IV were given lead acetate @ 1 PPM, 100 PPM and 1000 PPM, in drinking deionised water respectively for 28 days. In group III and IV dose dependant significant (P<0.05 reductions in TEC, Hb, PCV and TLC were observed. No significant change was observed in neutrophil, eosinophil, basophil and monocyte count in any treatment groups, whereas the lymphocyte count decreased significantly (P<0.05 in group III and IV. A dose dependant significant (P<0.05 increase in AST, ALP, AKP, GGT, BUN and creatinine was experiential while TP and albumin levels were decreased in group III and IV. [Vet World 2009; 2(11.000: 429-431

  13. Association between lead exposure from electronic waste recycling and child temperament alterations.

    Science.gov (United States)

    Liu, Junxiao; Xu, Xijin; Wu, Kusheng; Piao, Zhongxian; Huang, Jinrong; Guo, Yongyong; Li, Weiqiu; Zhang, Yuling; Chen, Aimin; Huo, Xia

    2011-08-01

    We aimed to evaluate the dose-dependent effects of lead exposure on temperament alterations in children from a primitive e-waste (obsolete electrical and electronic devices) recycling area in Guiyu of China and a control area (Chendian, China). Blood lead levels (BLL) might be correlated with temperament, health, and relevant factors that were evaluated through Parent Temperament Questionnaire (PTQ), physical examination, and residential questionnaires. We collected venipuncture blood samples from 303 children (aged 3-7 years old) between January and February 2008. Child BLL were higher in Guiyu than in Chendian (median 13.2 μg/dL, range 4.0-48.5 μg/dL vs. 8.2 μg/dL, 0-21.3 μg/dL) (Pchildren (all Pchildren with low BLL (BLLchildren by increasing BLL and altering children temperament, although the exposure to other toxicants needs to be examined in future studies. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Short-term sleep deprivation leads to decreased systemic redox metabolites and altered epigenetic status.

    Science.gov (United States)

    Trivedi, Malav S; Holger, Dana; Bui, Anh Tuyet; Craddock, Travis J A; Tartar, Jaime L

    2017-01-01

    Sleep is critical for repair as well as the rejuvenation processes in the body and many of these functions are regulated via underlying cellular metabolic homeostasis. Changes in sleep pattern are reported to alter such metabolic function resulting in altered disease susceptibility or behavior. Here, we measured the extent to which overnight total sleep deprivation (SD) in young adult humans can influence systemic (plasma-derived) redox-metabolism including the major antioxidant, glutathione as well as DNA methylation levels. Nineteen participants (n = 19, μ age = 21, SD = 3.09) underwent morning testing before and after overnight total SD. Biochemical measures before and after SD revealed that glutathione, ATP, cysteine, and homocysteine levels were significantly reduced following one night of sleep deprivation (all p's sleep deprivation (maintaining wakefulness) uses up metabolic reserves, we observed that morning cortisol levels were blunted after sleep deprivation. There were no significant correlations between self-reported or actigraphy-measured sleep and the biochemical measurements, strongly indicating that prior sleep behavior did not have any direct influence on the biochemical measures taken at baseline or after sleep deprivation. Results from the current investigation supports the previous literature implicating the induction of oxidative stress and ATP depletion with sleep deprivation. Furthermore, such altered antioxidant status can also induce downstream epigenetic changes. Although we did not measure the specific genes that were altered under the influence of such sleep deprivation, such epigenetic changes could potentially contribute towards disease predisposition.

  15. Altered miRNA expression in the cervix during pregnancy associated with lead and mercury exposure

    Science.gov (United States)

    Sanders, Alison P; Burris, Heather H; Just, Allan C; Motta, Valeria; Amarasiriwardena, Chitra; Svensson, Katherine; Oken, Emily; Solano-Gonzalez, Maritsa; Mercado-Garcia, Adriana; Pantic, Ivan; Schwartz, Joel; Tellez-Rojo, Martha M; Baccarelli, Andrea A; Wright, Robert O

    2015-01-01

    Aim: Toxic metals including lead and mercury are associated with adverse pregnancy outcomes. This study aimed to assess the association between miRNA expression in the cervix during pregnancy with lead and mercury levels. Materials & methods: We obtained cervical swabs from pregnant women (n = 60) and quantified cervical miRNA expression. Women's blood lead, bone lead and toenail mercury levels were analyzed. We performed linear regression to examine the association between metal levels and expression of 74 miRNAs adjusting for covariates. Results: Seventeen miRNAs were negatively associated with toenail mercury levels, and tibial bone lead levels were associated with decreased expression of miR-575 and miR-4286. Conclusion: The findings highlight miRNAs in the human cervix as novel responders to maternal chemical exposure during pregnancy. PMID:26418635

  16. Loss of spatacsin function alters lysosomal lipid clearance leading to upper and lower motor neuron degeneration.

    Science.gov (United States)

    Branchu, Julien; Boutry, Maxime; Sourd, Laura; Depp, Marine; Leone, Céline; Corriger, Alexandrine; Vallucci, Maeva; Esteves, Typhaine; Matusiak, Raphaël; Dumont, Magali; Muriel, Marie-Paule; Santorelli, Filippo M; Brice, Alexis; El Hachimi, Khalid Hamid; Stevanin, Giovanni; Darios, Frédéric

    2017-06-01

    Mutations in SPG11 account for the most common form of autosomal recessive hereditary spastic paraplegia (HSP), characterized by a gait disorder associated with various brain alterations. Mutations in the same gene are also responsible for rare forms of Charcot-Marie-Tooth (CMT) disease and progressive juvenile-onset amyotrophic lateral sclerosis (ALS). To elucidate the physiopathological mechanisms underlying these human pathologies, we disrupted the Spg11 gene in mice by inserting stop codons in exon 32, mimicking the most frequent mutations found in patients. The Spg11 knockout mouse developed early-onset motor impairment and cognitive deficits. These behavioral deficits were associated with progressive brain atrophy with the loss of neurons in the primary motor cortex, cerebellum and hippocampus, as well as with accumulation of dystrophic axons in the corticospinal tract. Spinal motor neurons also degenerated and this was accompanied by fragmentation of neuromuscular junctions and muscle atrophy. This new Spg11 knockout mouse therefore recapitulates the full range of symptoms associated with SPG11 mutations observed in HSP, ALS and CMT patients. Examination of the cellular alterations observed in this model suggests that the loss of spatacsin leads to the accumulation of lipids in lysosomes by perturbing their clearance from these organelles. Altogether, our results link lysosomal dysfunction and lipid metabolism to neurodegeneration and pinpoint a critical role of spatacsin in lipid turnover. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. PFOS induces behavioral alterations, including spontaneous hyperactivity that is corrected by dexamfetamine in zebrafish larvae.

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    Stefan Spulber

    Full Text Available Perfluorooctane sulfonate (PFOS is a widely spread environmental contaminant. It accumulates in the brain and has potential neurotoxic effects. The exposure to PFOS has been associated with higher impulsivity and increased ADHD prevalence. We investigated the effects of developmental exposure to PFOS in zebrafish larvae, focusing on the modulation of activity by the dopaminergic system. We exposed zebrafish embryos to 0.1 or 1 mg/L PFOS (0.186 or 1.858 µM, respectively and assessed swimming activity at 6 dpf. We analyzed the structure of spontaneous activity, the hyperactivity and the habituation during a brief dark period (visual motor response, and the vibrational startle response. The findings in zebrafish larvae were compared with historical data from 3 months old male mice exposed to 0.3 or 3 mg/kg/day PFOS throughout gestation. Finally, we investigated the effects of dexamfetamine on the alterations in spontaneous activity and startle response in zebrafish larvae. We found that zebrafish larvae exposed to 0.1 mg/L PFOS habituate faster than controls during a dark pulse, while the larvae exposed to 1 mg/L PFOS display a disorganized pattern of spontaneous activity and persistent hyperactivity. Similarly, mice exposed to 0.3 mg/kg/day PFOS habituated faster than controls to a new environment, while mice exposed to 3 mg/kg/day PFOS displayed more intense and disorganized spontaneous activity. Dexamfetamine partly corrected the hyperactive phenotype in zebrafish larvae. In conclusion, developmental exposure to PFOS in zebrafish induces spontaneous hyperactivity mediated by a dopaminergic deficit, which can be partially reversed by dexamfetamine in zebrafish larvae.

  18. Comparison of lead isotopes with source apportionment models, including SOM, for air particulates

    International Nuclear Information System (INIS)

    Gulson, Brian; Korsch, Michael; Dickson, Bruce; Cohen, David; Mizon, Karen; Michael Davis, J.

    2007-01-01

    We have measured high precision lead isotopes in PM 2.5 particulates from a highly-trafficked site (Mascot) and rural site (Richmond) in the Sydney Basin, New South Wales, Australia to compare with isotopic data from total suspended particulates (TSP) from other sites in the Sydney Basin and evaluate relationships with source fingerprints obtained from multi-element PM 2.5 data. The isotopic data for the period 1998 to 2004 show seasonal peaks and troughs that are more pronounced in the rural site for the PM 2.5 .samples but are consistent with the TSP. The Self Organising Map (SOM) method has been applied to the multi-element PM 2.5 data to evaluate its use in obtaining fingerprints for comparison with standard statistical procedures (ANSTO model). As seasonal effects are also significant for the multi-element data, the SOM modelling is reported as site and season dependent. At the Mascot site, the ANSTO model exhibits decreasing 206 Pb/ 204 Pb ratios with increasing contributions of fingerprints for 'secondary smoke' (industry), 'soil', 'smoke' and 'seaspray'. Similar patterns were shown by SOM winter fingerprints for both sites. At the rural site, there are large isotopic variations but for the majority of samples these are not associated with increased contributions from the main sources with the ANSTO model. For two winter sampling times, there are increased contributions from 'secondary industry', 'smoke', 'soil' and seaspray with one time having a source or sources of Pb similar to that of Mascot. The only positive relationship between increasing 206 Pb/ 204 Pb ratio and source contributions is found at the rural site using the SOM summer fingerprints, both of which show a significant contribution from sulphur. Several of the fingerprints using either model have significant contributions from black carbon (BC) and/or sulphur (S) that probably derive from diesel fuels and industrial sources. Increased contributions from sources with the SOM summer

  19. Wheat root length and not branching is altered in the presence of neighbours, including blackgrass

    Science.gov (United States)

    Finch, Jessica A.; Guillaume, Gaëtan; French, Stephanie A.; Colaço, Renato D. D. R.; Davies, Julia M.

    2017-01-01

    The effect of neighbouring plants on crop root system architecture may directly interfere with water and nutrient acquisition, yet this important and interesting aspect of competition remains poorly understood. Here, the effect of the weed blackgrass (Alopecurus myosuroides Huds.) on wheat (Triticum aestivum L.) roots was tested, since a low density of this species (25 plants m-2) can lead to a 10% decrease in wheat yield and herbicide resistance is problematic. We used a simplified growth system based on gelled medium, to grow wheat alongside a neighbour, either another wheat plant, a blackgrass or Brachypodium dystachion individual (a model grass). A detailed analysis of wheat seminal root system architecture showed that the presence of a neighbour principally affected the root length, rather than number or diameter under a high nutrient regime. In particular, the length of first order lateral roots decreased significantly in the presence of blackgrass and Brachypodium. However, this effect was not noted when wheat plants were grown in low nutrient conditions. This suggests that wheat may be less sensitive to the presence of blackgrass when grown in low nutrient conditions. In addition, nutrient availability to the neighbour did not modulate the neighbour effect on wheat root architecture. PMID:28542446

  20. A Tox21 Approach to Altered Epigenetic Landscapes: Assessing Epigenetic Toxicity Pathways Leading to Altered Gene Expression and Oncogenic Transformation In Vitro

    Directory of Open Access Journals (Sweden)

    Craig L. Parfett

    2017-06-01

    Full Text Available An emerging vision for toxicity testing in the 21st century foresees in vitro assays assuming the leading role in testing for chemical hazards, including testing for carcinogenicity. Toxicity will be determined by monitoring key steps in functionally validated molecular pathways, using tests designed to reveal chemically-induced perturbations that lead to adverse phenotypic endpoints in cultured human cells. Risk assessments would subsequently be derived from the causal in vitro endpoints and concentration vs. effect data extrapolated to human in vivo concentrations. Much direct experimental evidence now shows that disruption of epigenetic processes by chemicals is a carcinogenic mode of action that leads to altered gene functions playing causal roles in cancer initiation and progression. In assessing chemical safety, it would therefore be advantageous to consider an emerging class of carcinogens, the epigenotoxicants, with the ability to change chromatin and/or DNA marks by direct or indirect effects on the activities of enzymes (writers, erasers/editors, remodelers and readers that convey the epigenetic information. Evidence is reviewed supporting a strategy for in vitro hazard identification of carcinogens that induce toxicity through disturbance of functional epigenetic pathways in human somatic cells, leading to inactivated tumour suppressor genes and carcinogenesis. In the context of human cell transformation models, these in vitro pathway measurements ensure high biological relevance to the apical endpoint of cancer. Four causal mechanisms participating in pathways to persistent epigenetic gene silencing were considered: covalent histone modification, nucleosome remodeling, non-coding RNA interaction and DNA methylation. Within these four interacting mechanisms, 25 epigenetic toxicity pathway components (SET1, MLL1, KDM5, G9A, SUV39H1, SETDB1, EZH2, JMJD3, CBX7, CBX8, BMI, SUZ12, HP1, MPP8, DNMT1, DNMT3A, DNMT3B, TET1, MeCP2, SETDB2, BAZ2

  1. A Tox21 Approach to Altered Epigenetic Landscapes: Assessing Epigenetic Toxicity Pathways Leading to Altered Gene Expression and Oncogenic Transformation In Vitro.

    Science.gov (United States)

    Parfett, Craig L; Desaulniers, Daniel

    2017-06-01

    An emerging vision for toxicity testing in the 21st century foresees in vitro assays assuming the leading role in testing for chemical hazards, including testing for carcinogenicity. Toxicity will be determined by monitoring key steps in functionally validated molecular pathways, using tests designed to reveal chemically-induced perturbations that lead to adverse phenotypic endpoints in cultured human cells. Risk assessments would subsequently be derived from the causal in vitro endpoints and concentration vs. effect data extrapolated to human in vivo concentrations. Much direct experimental evidence now shows that disruption of epigenetic processes by chemicals is a carcinogenic mode of action that leads to altered gene functions playing causal roles in cancer initiation and progression. In assessing chemical safety, it would therefore be advantageous to consider an emerging class of carcinogens, the epigenotoxicants, with the ability to change chromatin and/or DNA marks by direct or indirect effects on the activities of enzymes (writers, erasers/editors, remodelers and readers) that convey the epigenetic information. Evidence is reviewed supporting a strategy for in vitro hazard identification of carcinogens that induce toxicity through disturbance of functional epigenetic pathways in human somatic cells, leading to inactivated tumour suppressor genes and carcinogenesis. In the context of human cell transformation models, these in vitro pathway measurements ensure high biological relevance to the apical endpoint of cancer. Four causal mechanisms participating in pathways to persistent epigenetic gene silencing were considered: covalent histone modification, nucleosome remodeling, non-coding RNA interaction and DNA methylation. Within these four interacting mechanisms, 25 epigenetic toxicity pathway components (SET1, MLL1, KDM5, G9A, SUV39H1, SETDB1, EZH2, JMJD3, CBX7, CBX8, BMI, SUZ12, HP1, MPP8, DNMT1, DNMT3A, DNMT3B, TET1, MeCP2, SETDB2, BAZ2A, UHRF1, CTCF

  2. Influence of minerals on lead-induced alterations in liver function in rats exposed to long-term lead exposure

    International Nuclear Information System (INIS)

    Herman, D'souza Sunil; Geraldine, Menezes; T, Venkatesh

    2009-01-01

    The objective of this study was to evaluate the role of minerals on lead-induced effect on the liver. Differentiation of minerals and heavy metals pose an inherent problem due to certain common properties shared by them. With this approach to the problem of heavy metal toxicity, in the present study two groups of male Wistar albino rats, one group (well-nourished) fed on mineral rich diet and other group (undernourished) fed on diet without mineral supplements were used. Both the groups of rats were subjected to long-term lead exposure. The diet of well-nourished group was supplemented with calcium (Ca); 1.2%, phosphorous (P); 0.6%, iron (Fe); 90 mg/kg, zinc (Zn); 50 mg/kg, magnesium (Mg); 0.08%, manganese (Mn); 70 mg/kg, selenium (Se); 0.2 mg/kg, copper (Cu); 5 mg/kg, molybdenum (Mo); 0.8 mg/kg, iodine (I); 0.6 mg/kg, cobalt (Co); 3.0 mg/kg. Their blood lead and parameters of liver function were monitored periodically. Results of the study showed a very high statistically significant increase (p < 0.001) in the blood lead (PbB) levels and liver function test parameters in the undernourished subjects compared to the well-nourished subjects. Nutritional management of lead poisoning is of importance since essential elements and toxic heavy metals may interact to minimize the absorption of lead.

  3. Protective and ameliorative effect of sea buckthorn leaf extract supplementation on lead induced hemato-biochemical alterations in Wistar rats

    Directory of Open Access Journals (Sweden)

    Rizwana Zargar

    2016-09-01

    Full Text Available Aim: To evaluate the protective and ameliorative effect of aqueous sea buckthorn leaf extract (SLE on hemato-biochemical profile in lead intoxicated Wistar rats. Materials and Methods: An experiment was conducted for 60 days. 36 adult male Wistar rats with a mean body weight of 177.8±12.6 g were divided into five groups and were subjected to various daily oral treatment regimens. Group I served as a negative control receiving only feed and water, Group II (positive control for lead received lead acetate at 250 ppm in drinking water, and Group III (positive control for SLE received SLE at 100 mg/kg b.wt. Animals in Group IV received a combination of lead acetate at 250 ppm in drinking water for the first 45 days and SLE at 100 mg/kg b.wt. throughout the experimental period of 60-day, and in Group V for the last 15 days of the trial after the administration of lead acetate until the first 45 days of the trial to study the protective and ameliorating effects of SLE, respectively. Blood samples were collected from retro-orbital fossa of each rat on 0th, 45th, and 60th day of the experiment for hemato-biochemical analysis including hemoglobin (Hb, packed cell volume (PCV, serum total protein, albumin, globulin, albumin:globulin ratio, cholesterol, urea, and creatinine. Results: Significantly (p<0.01 lower levels of serum total proteins and albumin, and a significantly (p<0.01 higher serum cholesterol, urea and creatinine levels were observed in Group II (lead intoxicated group in comparison to Group I (negative control. Administration of SLE at 100 mg/kg body wt. to lead intoxicated Wistar rats resulted in normalization of almost all the biochemical parameters studied in both the treatment Groups, i.e., IV and V (protective and ameliorative. However, the effects were more pronounced in the protective group. No effects of SLE supplementation were observed on Hb levels. PCV levels improved in protective groups, but no effect was observed in

  4. Interleukin-18 Amplifies Macrophage Polarization and Morphological Alteration, Leading to Excessive Angiogenesis

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    Takuro Kobori

    2018-03-01

    Full Text Available M2 macrophage (Mφ promotes pathologic angiogenesis through a release of pro-angiogenic mediators or the direct cell–cell interaction with endothelium in the micromilieu of several chronic inflammatory diseases, including rheumatoid arthritis and cancer, where interleukin (IL-18 also contributes to excessive angiogenesis. However, the detailed mechanism remains unclear. The aim of this study is to investigate the mechanism by which M2 Mφs in the micromilieu containing IL-18 induce excessive angiogenesis in the in vitro experimental model using mouse Mφ-like cell line, RAW264.7 cells, and mouse endothelial cell line, b.End5 cells. We discovered that IL-18 acts synergistically with IL-10 to amplify the production of Mφ-derived mediators like osteopontin (OPN and thrombin, yielding thrombin-cleaved form of OPN generation, which acts through integrins α4/α9, thereby augmenting M2 polarization of Mφ with characteristics of increasing surface CD163 expression in association with morphological alteration. Furthermore, the results of visualizing temporal behavior and morphological alteration of Mφs during angiogenesis demonstrated that M2-like Mφs induced excessive angiogenesis through the direct cell–cell interaction with endothelial cells, possibly mediated by CD163.

  5. Growth-Related Neural Reorganization and the Autism Phenotype: A Test of the Hypothesis that Altered Brain Growth Leads to Altered Connectivity

    Science.gov (United States)

    Lewis, John D.; Elman, Jeffrey L.

    2008-01-01

    Theoretical considerations, and findings from computational modeling, comparative neuroanatomy and developmental neuroscience, motivate the hypothesis that a deviant brain growth trajectory will lead to deviant patterns of change in cortico-cortical connectivity. Differences in brain size during development will alter the relative cost and…

  6. Bisphenol A in oocytes leads to growth suppression and altered stress performance in juvenile rainbow trout.

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    Neelakanteswar Aluru

    Full Text Available BACKGROUND: Bisphenol A (BPA, used in the manufacture of plastics, is ubiquitously distributed in the aquatic environment. However, the effect of maternal transfer of these xenobiotics on embryonic development and growth is poorly understood in fish. We tested the hypothesis that BPA in eggs, mimicking maternal transfer, impact development, growth and stress performance in juveniles of rainbow trout (Oncorhynchus mykiss. METHODOLOGY/PRINCIPAL FINDINGS: Trout oocytes were exposed to 0, 30 and 100 microg.mL(-1 BPA for 3 h in ovarian fluid, followed by fertilization. The embryos were maintained in clean water and sampled temporally over 156-days post-fertilization (dpf, and juveniles were sampled at 400-dpf. The egg BPA levels declined steadily after exposure and were undetectable after 21- dpf. Oocyte exposure to BPA led to a delay in hatching and yolk absorption and a consistently lower body mass over 152-dpf. The growth impairment, especially in the high BPA group, correlated with higher growth hormone (GH content and lower GH receptors gene expression. Also, mRNA abundances of insulin-like growth factors (IGF-1 and IGF-2 and their receptors were suppressed in the BPA treated groups. The juvenile fish grown from the BPA-enriched eggs had lower body mass and showed perturbations in plasma cortisol and glucose response to an acute stressor. CONCLUSION: BPA accumulation in eggs, prior to fertilization, leads to hatching delays, growth suppression and altered stress response in juvenile trout. The somatotropic axis appears to be a key target for BPA impact during early embryogenesis, leading to long term growth and stress performance defects in fish.

  7. Gastric acid reduction leads to an alteration in lower intestinal microflora

    Energy Technology Data Exchange (ETDEWEB)

    Kanno, Takayuki [Department of Gastroenterology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-city, Wakayama 641-0012 (Japan); Matsuki, Takahiro [Yakult Central Institute for Microbiological Research, Tokyo (Japan); Oka, Masashi; Utsunomiya, Hirotoshi [Department of Gastroenterology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-city, Wakayama 641-0012 (Japan); Inada, Kenichi [First Department of Pathology, Fujita Health University School of Medicine, Aichi (Japan); Magari, Hirohito; Inoue, Izumi; Maekita, Takao; Ueda, Kazuki; Enomoto, Shotaro; Iguchi, Mikitaka; Yanaoka, Kimihiko; Tamai, Hideyuki [Department of Gastroenterology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-city, Wakayama 641-0012 (Japan); Akimoto, Shigeru [Department of Microbiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-city, Wakayama 641-0012 (Japan); Nomoto, Koji; Tanaka, Ryuichiro [Yakult Central Institute for Microbiological Research, Tokyo (Japan); Ichinose, Masao, E-mail: ichinose@wakayama-med.ac.jp [Department of Gastroenterology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-city, Wakayama 641-0012 (Japan)

    2009-04-17

    To clarify the alterations in lower intestinal microflora induced by gastric acid reduction, the dynamics of 12 major genera or groups of bacteria comprising the microflora in feces and colonic contents were examined by quantitative real-time PCR in proton pump inhibitor-treated rats and in asymptomatic human subjects with hypochlorhydria. In both rat and human experiments, most genera or groups of intestinal microflora (facultative and obligate anaerobes) proliferated by gastric acid reduction, and marked and significant increases in the Lactobacilli group and Veillonella, oropharyngeal bacteria, were observed. In rats, potent gastric acid inhibition led to a marked and significant increase of intestinal bacteria, including the Bacteroidesfragilis group, while Bifidobacterium, a beneficial bacterial species, remained at a constant level. These results strongly indicate that the gastric acid barrier not only controls the colonization and growth of oropharyngeal bacteria, but also regulates the population and composition of lower intestinal microflora.

  8. Gastric acid reduction leads to an alteration in lower intestinal microflora

    International Nuclear Information System (INIS)

    Kanno, Takayuki; Matsuki, Takahiro; Oka, Masashi; Utsunomiya, Hirotoshi; Inada, Kenichi; Magari, Hirohito; Inoue, Izumi; Maekita, Takao; Ueda, Kazuki; Enomoto, Shotaro; Iguchi, Mikitaka; Yanaoka, Kimihiko; Tamai, Hideyuki; Akimoto, Shigeru; Nomoto, Koji; Tanaka, Ryuichiro; Ichinose, Masao

    2009-01-01

    To clarify the alterations in lower intestinal microflora induced by gastric acid reduction, the dynamics of 12 major genera or groups of bacteria comprising the microflora in feces and colonic contents were examined by quantitative real-time PCR in proton pump inhibitor-treated rats and in asymptomatic human subjects with hypochlorhydria. In both rat and human experiments, most genera or groups of intestinal microflora (facultative and obligate anaerobes) proliferated by gastric acid reduction, and marked and significant increases in the Lactobacilli group and Veillonella, oropharyngeal bacteria, were observed. In rats, potent gastric acid inhibition led to a marked and significant increase of intestinal bacteria, including the Bacteroidesfragilis group, while Bifidobacterium, a beneficial bacterial species, remained at a constant level. These results strongly indicate that the gastric acid barrier not only controls the colonization and growth of oropharyngeal bacteria, but also regulates the population and composition of lower intestinal microflora.

  9. Altered immune response in mallard ducklings exposed to lead through maternal transfer in the wild

    International Nuclear Information System (INIS)

    Vallverdú-Coll, Núria; López-Antia, Ana; Martinez-Haro, Monica; Ortiz-Santaliestra, Manuel E.; Mateo, Rafael

    2015-01-01

    Lead (Pb) poisoning has caused significant mortality in waterfowl populations worldwide. In spite of having been banned since 2003, prevalence of Pb shot ingestion in mallards (Anas platyrhynchos) from the Ebro delta was still 15.5% in 2011–12. We collected mallard eggs from this area to study the effects of maternally transferred Pb on eggshell properties and on immune response and oxidative balance of ducklings. Eggshell Pb levels were positively correlated with Pb levels in the blood of ducklings. Ducklings with blood Pb levels above 180 ng mL −1 showed reduced body mass and died during the first week post hatching. Blood Pb levels positively correlated with humoral immune response, endogenous antioxidants and oxidative stress biomarkers, and negatively correlated with cellular immune response. Pb shot ingestion in birds can result in maternal transfer to the offspring that can affect their developing immune system and reduce their survival in early life stages. - Highlights: • Pb was transferred from mallard hens to eggs and ducklings. • Maternal Pb transfer was enough to inhibit blood ALAD activity in ducklings. • Cellular immune response was negatively affected by blood Pb levels. • Humoral immune response was exacerbated by Pb exposure. • Pb induced oxidative stress and increased levels of antioxidants in blood. - Maternal transfer of Pb alters immune responses and oxidative balance of ducklings and compromises the survival of individuals

  10. Protective effect of thymoquinone against lead-induced antioxidant defense system alteration in rat liver.

    Science.gov (United States)

    Mabrouk, Aymen

    2017-09-01

    Alteration of the antioxidant system may be related to lead (Pb) hepatotoxicity. This study was carried out to investigate the possible beneficial effect of thymoquinone (TQ), the major active ingredient of volatile oil of Nigella sativa seeds, against Pb-induced liver antioxidant defense system impairment. Adult male rats were randomized into four groups: control group received no treatment, Pb group was exposed to 2000 ppm of Pb acetate in drinking water, Pb-TQ group was cotreated with Pb plus TQ (5 mg/kg/day, per os) and TQ group receiving only TQ. All treatments were applied for five weeks. TQ alone did not induce any significant changes in the enzymatic and non-enzymatic antioxidant status. By contrast, Pb exposure significantly decreased not only reduced glutathione level, but also superoxide dismutase, glutathione peroxidase, catalase and glutathione reductase activities in the liver tissue. Interestingly, when coadministrated with Pb, TQ significantly improved the affected antioxidant parameters. In conclusion, our results indicate a protective effect of TQ against Pb-induced liver antioxidant capacity impairment and suggest that this component might be a clinically promising alternative in Pb hepatotoxicity.

  11. Pacemaker stimulus amplitude alteration without loss of capture: an unusual ECG finding in cardiac tamponade from pacemaker lead perforation.

    Science.gov (United States)

    Suksaranjit, P; Prasidthrathsint, K

    2014-01-01

    A variation in pacemaker stimulus amplitude can represent pacemaker system dysfunction from generator malfunction, lead insulation defect, lead fracture, or artefact of digital signal processing of the electrocardiography recorder. Pacemaker lead perforation into the pericardial space typically results in loss of capture which was not demonstrated in our patient. In summary, we report an unusual ECG finding of pacemaker stimulus amplitude alteration without loss of capture in the setting of cardiac tamponade from pacemaker lead perforation. Copyright © 2013 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  12. Lead

    Science.gov (United States)

    ... about the health effects of lead in drinking water The law mandates no-lead products for drinking water after ... Waste, and Cleanup Lead Mold Pesticides Radon Science Water A-Z Index Laws & Regulations By Business Sector By Topic Compliance Enforcement ...

  13. Sublethal Lead Exposure Alters Movement Behavior in Free-Ranging Golden Eagles.

    Science.gov (United States)

    Ecke, Frauke; Singh, Navinder J; Arnemo, Jon M; Bignert, Anders; Helander, Björn; Berglund, Åsa M M; Borg, Hans; Bröjer, Caroline; Holm, Karin; Lanzone, Michael; Miller, Tricia; Nordström, Åke; Räikkönen, Jannikke; Rodushkin, Ilia; Ågren, Erik; Hörnfeldt, Birger

    2017-05-16

    Lead poisoning of animals due to ingestion of fragments from lead-based ammunition in carcasses and offal of shot wildlife is acknowledged globally and raises great concerns about potential behavioral effects leading to increased mortality risks. Lead levels in blood were correlated with progress of the moose hunting season. Based on analyses of tracking data, we found that even sublethal lead concentrations in blood (25 ppb, wet weight), can likely negatively affect movement behavior (flight height and movement rate) of free-ranging scavenging Golden Eagles (Aquila chrysaetos). Lead levels in liver of recovered post-mortem analyzed eagles suggested that sublethal exposure increases the risk of mortality in eagles. Such adverse effects on animals are probably common worldwide and across species, where game hunting with lead-based ammunition is widespread. Our study highlights lead exposure as a considerably more serious threat to wildlife conservation than previously realized and suggests implementation of bans of lead ammunition for hunting.

  14. Delayed neurogenesis leads to altered specification of ventrotemporal retinal ganglion cells in albino mice

    Science.gov (United States)

    2014-01-01

    Background Proper binocular vision depends on the routing at the optic chiasm of the correct proportion of retinal ganglion cell (RGC) axons that project to the same (ipsilateral) and opposite (contralateral) side of the brain. The ipsilateral RGC projection is reduced in mammals with albinism, a congenital disorder characterized by deficient pigmentation in the skin, hair, and eyes. Compared to the pigmented embryonic mouse retina, the albino embryonic mouse retina has fewer RGCs that express the zinc-finger transcription factor, Zic2, which is transiently expressed by RGCs fated to project ipsilaterally. Here, using Zic2 as a marker of ipsilateral RGCs, Islet2 as a marker of contralateral RGCs, and birthdating, we investigate spatiotemporal dynamics of RGC production as they relate to the phenotype of diminished ipsilateral RGC number in the albino retina. Results At embryonic day (E)15.5, fewer Zic2-positive (Zic2+) RGCs are found in the albino ventrotemporal (VT) retina compared with the pigmented VT retina, as we previously reported. However, the reduction in Zic2+ RGCs in the albino is not accompanied by a compensatory increase in Zic2-negative (Zic2−) RGCs, resulting in fewer RGCs in the VT retina at this time point. At E17.5, however, the number of RGCs in the VT region is similar in pigmented and albino retinae, implicating a shift in the timing of RGC production in the albino. Short-term birthdating assays reveal a delay in RGC production in the albino VT retina between E13 and E15. Specifically, fewer Zic2+ RGCs are born at E13 and more Zic2− RGCs are born at E15. Consistent with an increase in the production of Zic2− RGCs born at later ages, more RGCs at E17.5 express the contralateral marker, Islet2, in the albino VT retina compared with the pigmented retina. Conclusions A delay in neurogenesis in the albino retina is linked to the alteration of RGC subtype specification and consequently leads to the reduced ipsilateral projection that

  15. Dietary magnesium deficiency alters gut microbiota and leads to depressive-like behaviour.

    Science.gov (United States)

    Winther, Gudrun; Pyndt Jørgensen, Betina M; Elfving, Betina; Nielsen, Denis Sandris; Kihl, Pernille; Lund, Sten; Sørensen, Dorte Bratbo; Wegener, Gregers

    2015-06-01

    Gut microbiota (GM) has previously been associated with alterations in rodent behaviour, and since the GM is affected by the diet, the composition of the diet may be an important factor contributing to behavioural changes. Interestingly, a magnesium restricted diet has been shown to induce anxiety and depressive-like behaviour in humans and rodents, and it could be suggested that magnesium deficiency may mediate the effects through an altered GM. The present study therefore fed C57BL/6 mice with a standard diet or a magnesium deficient diet (MgD) for 6 weeks, followed by behavioural testing in the forced swim test (FST) to evaluate depressive-like behaviour. An intraperitoneal glucose tolerance test (GTT) was performed 2 day after the FST to assess metabolic alterations. Neuroinflammatory markers were analysed from hippocampus. GM composition was analysed and correlated to the behaviour and hippocampal markers. It was found that mice exposed to MgD for 6 weeks were more immobile than control mice in the FST, suggesting an increased depressive-like behaviour. No significant difference was detected in the GTT. GM composition correlated positively with the behaviour of undisturbed C57BL/6 mice, feeding MgD diet altered the microbial composition. The altered GM correlated positively to the hippocampal interleukin-6. In conclusion, we hypothesise that imbalances of the microbiota-gut-brain axis induced by consuming a MgD diet, contributes to the development of depressive-like behaviour.

  16. Exposure to sublethal levels of waterborne lead alters reproductive behavior patterns in fathead minnows (Pimephales promelas).

    Science.gov (United States)

    Weber, D N

    1993-01-01

    Lead (Pb) caused multiple effects on reproductive behavior and overall reproductive success. Adult fathead minnows (Pimephales promelas) were acclimated at a 16L:8D photoperiod to stimulate reproductive development. Reproductively mature adults were separated as male-female pairs and maintained for 4 weeks in either 0.0 or 0.5 ppm Pb. High lead accumulations occurred in testes and ovaries of treated fish; lead concentrations in control fish gonads were not detectable. Lead suppressed spermatocyte production and retarded ovarian development, although no lead-induced gonadosomatic index changes for either sex were noted. Lead decreased the number of eggs oviposited, increased interspawn periods and suppressed embryo development. Control males displayed maximum secondary sex characteristic development (banding, tubercle formation, head and eye darkening); lead-exposed fish displayed less. Control males spent more time in ceiling-directed behaviors associated with nest preparation and maintenance than lead-exposed. These variables were affected differentially with respect to stage of reproductive maturity at time of lead exposure, i.e., fish displaying greater secondary sex characteristic development before exposure were less affected by lead than those fish that showed less development.

  17. Dietary magnesium deficiency alters gut microbiota and leads to depressive-like behaviour

    DEFF Research Database (Denmark)

    Winther, Gudrun; Jørgensen, Betina M. Pyndt; Elfving, Betina

    2015-01-01

    by behavioural testing in the forced swim test (FST) to evaluate depressive-like behaviour. An intraperitoneal glucose tolerance test (GTT) was performed 2 day after the FST to assess metabolic alterations. Neuroinflammatory markers were analysed from hippocampus. GM composition was analysed and correlated...

  18. Numerical and experimental study on the ability of dynamic roughness to alter the development of a leading edge vortex

    Science.gov (United States)

    Griffin, Christopher D.

    Dynamic stall is an unsteady aerodynamic phenomenon garnering much research interest because it occurs in a variety of applications. For example, dynamic stall is known to occur on helicopter rotor blades, wind turbines, high maneuvering military aircraft, and flapping wings. Dynamic stall occurs when an aerodynamic lifting device, such as an airfoil, wing, or turbomachine blade, undergoes a rapid pitching motion. It also occurs on lifting devices that are impulsively started at high angles of attack. Dynamic stall can "delay" aerodynamic stall to angles of attack that are significantly beyond the static stall angle of attack. During dynamic stall a large leading edge vortex (LEV) is formed, which creates greater fluid acceleration over the wing or airfoil, thus sustaining lift. As this vortex is shed downstream stall eventually occurs and there is an abrupt increase in drag and a large shift in pitching moment. Research has been performed to better understand the mechanisms occurring during dynamic stall in an effort to find ways to best take advantage of the increased lift associated with dynamic stall, but avoid the downfalls that occur once stall is initiated. Few attempts have been made to alter the LEV, and these attempts have used methods associated with laminar boundary layer separation control. Although these methods have shown promise, they suffer from the drawback that they exhaust more energy than is gained by flow control, while also only being effective at certain flight regimes. The research described herein documents the first study on the ability of dynamic roughness to alter the LEV encountered on a rapidly pitching airfoil. Both numerical and experimental studies were performed, including two-dimensional and three-dimensional computational fluid dynamics (CFD) simulations as well as stereo and planar particle image velocimetry (PIV) experiments. Evidence for the ability of small scale dynamic roughness to alter the development of the LEV was

  19. Memory blindness: Altered memory reports lead to distortion in eyewitness memory.

    Science.gov (United States)

    Cochran, Kevin J; Greenspan, Rachel L; Bogart, Daniel F; Loftus, Elizabeth F

    2016-07-01

    Choice blindness refers to the finding that people can often be misled about their own self-reported choices. However, little research has investigated the more long-term effects of choice blindness. We examined whether people would detect alterations to their own memory reports, and whether such alterations could influence participants' memories. Participants viewed slideshows depicting crimes, and then either reported their memories for episodic details of the event (Exp. 1) or identified a suspect from a lineup (Exp. 2). Then we exposed participants to manipulated versions of their memory reports, and later tested their memories a second time. The results indicated that the majority of participants failed to detect the misinformation, and that exposing witnesses to misleading versions of their own memory reports caused their memories to change to be consistent with those reports. These experiments have implications for eyewitness memory.

  20. Human giant congenital melanocytic nevus exhibits potential proteomic alterations leading to melanotumorigenesis

    Directory of Open Access Journals (Sweden)

    Kim Hyoung Kyu

    2012-08-01

    Full Text Available Abstract Background A giant congenital melanocytic nevus (GCMN is a malformation of the pigment cells. It is a distress to the patients for two reasons: one is disfigurement, and the other is the possibility of malignant changes. However, the underlying mechanisms of the development of GCMN and melanotumorigenesis in GCMN are unknown. Hence, the aim of this study was to identify the proteomic alterations and associated functional pathways in GCMN. Results Proteomic differences between GCMN (n = 3 and normal skin samples (n = 3 were analyzed by one-dimensional-liquid chromatography-tandem mass spectrometry Relative levels of the selected proteins were validated using western blot analysis. The biological processes associated with the abundance modified proteins were analyzed using bioinformatic tools. Among the 46 abundance modified proteins, expression of 4 proteins was significantly downregulated and expression of 42 proteins was significantly upregulated in GCMN compared to normal skin samples (p  Conclusion These findings suggest that GCMN exhibits potential proteomic alterations, which may play a role in melanotumorigenesis, and the significant alteration of 14-3-3 family proteins could be a key regulator of the biological pathway remodeling in GCMN.

  1. Does moderate preterm birth lead to altered arterial pressure? Studies in sheep.

    Science.gov (United States)

    De Matteo, Robert; Stacy, Victoria; Probyn, Megan E; Brew, Nadine; Blasch, Natasha; Harding, Richard

    2008-12-01

    1. Low birth weight (LBW) is associated with an increased risk of cardiovascular disease. Preterm birth is a major determinant of LBW and has been shown to result in elevated arterial pressure (AP) in humans, but few studies have investigated the effects of preterm birth in the absence of potentially confounding factors. Our aim was to determine whether moderately preterm birth per se alters the postnatal development of AP in lambs. 2. Preterm lambs were delivered approximately 14 days before term (i.e. approximately 133 days of gestation); controls were born at term (approximately 147 days). Mean arterial pressure (MAP), heart rate (HR), blood composition and indices of growth were measured at 4 and 8 weeks post term-equivalent age (PTEA). We also studied a separate cohort of preterm and term sheep as young adults (approximately 1.1 years). 3. Preterm lambs had significantly lower birth weights than term lambs, but bodyweights were not significantly different by Day 12 PTEA. In addition, MAP, HR and most blood variables did not differ between term and preterm lambs at 4 or 8 weeks PTEA. Preterm birth per se did not alter MAP or HR in young adult sheep. 4. Low birth weight due to preterm birth does not result in an altered AP during early postnatal life or at maturity. Moderate intrauterine growth restriction (IUGR) due to twinning, which further reduces birth weight, does not affect MAP in preterm lambs. Other factors, such as the degree of prematurity or IUGR, exposure to corticosteroids or postnatal nutrition, may be important in the later development of elevated AP.

  2. Increased corticosterone in peripubertal rats leads to long-lasting alterations in social exploration and aggression

    Directory of Open Access Journals (Sweden)

    Vandana eVeenit

    2013-04-01

    Full Text Available Stress during childhood and adolescence enhances the risk of psychopathology later in life. We have previously shown that subjecting male rats to stress during the peripubertal period induces long-lasting effects on emotion and social behaviors. As corticosterone is increased by stress and known to exert important programming effects, we reasoned that increasing corticosterone might mimic the effects of peripubertal stress. To this end, we injected corticosterone (5 mg/kg on 7 scattered days during the peripuberty period (P28-P30, P34, P36, P40 and P42, following the same experimental schedule as for stress administration in our peripubertal paradigm. We measured play behavior in the homecage and, at adulthood, the corticosterone response to novelty and behavioral responses in tests for anxiety- and depression-like behaviors, aggression and social exploration. As compared to vehicle, corticosterone-treated animals exhibit more aggressive play behavior during adolescence, increased aggressive behavior in a resident-intruder test while reduced juvenile exploration and corticosterone reactivity at adulthood. Whereas the corticosterone treatment mimicked alterations induced by the peripuberty stress protocol in the social domain, it did not reproduce previously observed effects of peripuberty stress on increasing anxiety-like and depression-like behaviors, respectively evaluated in the elevated plus maze and the forced swim tests. Our findings indicate that increasing corticosterone levels during peripuberty might be instrumental to program alterations in the social domain observed following stress, whereas other factors might need to be recruited for the programming of long-term changes in emotionality. Our study opens the possibility that individual differences on the degree of glucocorticoid activation during peripuberty might be central to defining differences in vulnerability to develop psychopathological disorders coursing with alterations in

  3. Do neural tube defects lead to structural alterations in the human bladder?

    Science.gov (United States)

    Pazos, Helena M F; Lobo, Márcio Luiz de P; Costa, Waldemar S; Sampaio, Francisco J B; Cardoso, Luis Eduardo M; Favorito, Luciano Alves

    2011-05-01

    Anencephaly is the most severe neural tube defect in human fetuses. The objective of this paper is to analyze the structure of the bladder in anencephalic human fetuses. We studied 40 bladders of normal human fetuses (20 male and 20 female, aged 14 to 23 WPC) and 12 bladders of anencephalic fetuses (5 male and 7 female, aged 18 to 22 WPC). The bladders were removed and processed by routine histological techniques. Stereological analysis of collagen, elastic system fibers and smooth muscle was performed in sections. Data were expressed as volumetric density (Vv-%). The images were captured with Olympus BX51 microscopy and Olympus DP70 camera. The stereological analysis was done using the software Image Pro and Image J. For biochemical analysis, samples were fixed in acetone, and collagen concentrations were expressed as micrograms of hydroxyproline per mg of dry tissue. Means were statistically compared using the unpaired t-test (p<0.05). We observed a significant increase (p<0.0001) in the Vv of collagen in the bladders of anencephalic fetuses (69.71%) when compared to normal fetuses (52.74%), and a significant decrease (p<0.0001) in the Vv of smooth muscle cells in the bladders of anencephalic fetuses (23.96%) when compared to normal fetuses (38.35%). The biochemical analyses showed a higher concentration of total collagen in the bladders of anencephalic fetuses (37354 µg/mg) when compared to normal fetuses (48117 µg/mg, p<0.02). The structural alterations of the bladder found in this study may suggest the existence of functional alterations in the bladder of anencephalic human fetuses.

  4. Progressive obesity leads to altered ovarian gene expression in the Lethal Yellow mouse: a microarray study

    Directory of Open Access Journals (Sweden)

    Brannian John

    2009-08-01

    Full Text Available Abstract Background Lethal yellow (LY; C57BL/6J Ay/a mice exhibit adult-onset obesity, altered metabolic regulation, and early reproductive senescence. The present study was designed to test the hypothesis that obese LY mice possess differences in expression of ovarian genes relative to age-matched lean mice. Methods 90- and 180-day-old LY and lean black (C57BL/6J a/a mice were suppressed with GnRH antagonist (Antide®, then stimulated with 5 IU eCG. cRNA derived from RNA extracts of whole ovarian homogenates collected 36 h post-eCG were run individually on Codelink Mouse Whole Genome Bioarrays (GE Healthcare Life Sciences. Results Fifty-two genes showed ≥ 2-fold differential (p Cyp51, and steroidogenic acute regulatory protein (Star. Fewer genes showed lower expression in LY mice, e.g. angiotensinogen. In contrast, none of these genes showed differential expression in 90-day-old LY and black mice, which are of similar body weight. Interestingly, 180-day-old LY mice had a 2-fold greater expression of 11beta-hydroxysteroid dehydrogenase type 1 (Hsd11b1 and a 2-fold lesser expression of 11beta-hydroxysteroid dehydrogenase type 2 (Hsd11b2, differences not seen in 90-day-old mice. Consistent with altered Hsd11b gene expression, ovarian concentrations of corticosterone (C were elevated in aging LY mice relative to black mice, but C levels were similar in young LY and black mice. Conclusion The data suggest that reproductive dysfunction in aging obese mice is related to modified intraovarian gene expression that is directly related to acquired obesity.

  5. An obesity-associated gut microbiome reprograms the intestinal epigenome and leads to altered colonic gene expression.

    Science.gov (United States)

    Qin, Yufeng; Roberts, John D; Grimm, Sara A; Lih, Fred B; Deterding, Leesa J; Li, Ruifang; Chrysovergis, Kaliopi; Wade, Paul A

    2018-01-23

    The gut microbiome, a key constituent of the colonic environment, has been implicated as an important modulator of human health. The eukaryotic epigenome is postulated to respond to environmental stimuli through alterations in chromatin features and, ultimately, gene expression. How the host mediates epigenomic responses to gut microbiota is an emerging area of interest. Here, we profile the gut microbiome and chromatin characteristics in colon epithelium from mice fed either an obesogenic or control diet, followed by an analysis of the resultant changes in gene expression. The obesogenic diet shapes the microbiome prior to the development of obesity, leading to altered bacterial metabolite production which predisposes the host to obesity. This microbiota-diet interaction leads to changes in histone modification at active enhancers that are enriched for binding sites for signal responsive transcription factors. These alterations of histone methylation and acetylation are associated with signaling pathways integral to the development of colon cancer. The transplantation of obesogenic diet-conditioned microbiota into germ free mice, combined with an obesogenic diet, recapitulates the features of the long-term diet regimen. The diet/microbiome-dependent changes are reflected in both the composition of the recipient animals' microbiome as well as in the set of transcription factor motifs identified at diet-influenced enhancers. These findings suggest that the gut microbiome, under specific dietary exposures, stimulates a reprogramming of the enhancer landscape in the colon, with downstream effects on transcription factors. These chromatin changes may be associated with those seen during colon cancer development.

  6. Lead induces chondrogenesis and alters transforming growth factor-beta and bone morphogenetic protein signaling in mesenchymal cell populations.

    Science.gov (United States)

    Zuscik, Michael J; Ma, Lin; Buckley, Taylor; Puzas, J Edward; Drissi, Hicham; Schwarz, Edward M; O'Keefe, Regis J

    2007-09-01

    It has been established that skeletal growth is stunted in lead-exposed children. Because chondrogenesis is a seminal step during skeletal development, elucidating the impact of Pb on this process is the first step toward understanding the mechanism of Pb toxicity in the skeleton. The aim of this study was to test the hypothesis that Pb alters chondrogenic commitment of mesenchymal cells and to assess the effects of Pb on various signaling pathways. We assessed the influence of Pb on chondrogenesis in murine limb bud mesenchymal cells (MSCs) using nodule formation assays and gene analyses. The effects of Pb on transforming growth factor-beta (TGF-beta) and bone morphogenetic protein (BMP) signaling was studied using luciferase-based reporters and Western analyses, and luciferase-based assays were used to study cyclic adenosine monophosphate response element binding protein (CREB), beta-catenin, AP-1, and nuclear factor-kappa B (NF-kappaB) signaling. We also used an ectopic bone formation assay to determine how Pb affects chondrogenesis in vivo. Pb-exposed MSCs showed enhanced basal and TGF-beta/BMP induction of chondrogenesis, evidenced by enhanced nodule formation and up-regulation of Sox-9, type 2 collagen, and aggrecan, all key markers of chondrogenesis. We observed enhanced chondrogenesis during ectopic bone formation in mice preexposed to Pb via drinking water. In MSCs, Pb enhanced TGF-beta but inhibited BMP-2 signaling, as measured by luciferase reporter assays and Western analyses of Smad phosphorylation. Although Pb had no effect on basal CREB or Wnt/beta-catenin pathway activity, it induced NFkappaB signaling and inhibited AP-1 signaling. The in vitro and in vivo induction of chondrogenesis by Pb likely involves modulation and integration of multiple signaling pathways including TGF-beta, BMP, AP-1, and NFkappaB.

  7. Aging leads to altered microglial function that reduces brain resiliency increasing vulnerability to neurodegenerative diseases.

    Science.gov (United States)

    Bickford, Paula C; Flowers, Antwoine; Grimmig, Bethany

    2017-08-01

    Aging is the primary risk factor for many neurodegenerative diseases. Thus, understanding the basic biological changes that take place with aging that lead to the brain being less resilient to disease progression of neurodegenerative diseases such as Parkinson's disease or Alzheimer's disease or insults to the brain such as stroke or traumatic brain injuries. Clearly this will not cure the disease per se, yet increasing the ability of the brain to respond to injury could improve long term outcomes. The focus of this review is examining changes in microglia with age and possible therapeutic interventions involving the use of polyphenol rich dietary supplements. Published by Elsevier Inc.

  8. Unilateral Eccentric Contraction of the Plantarflexors Leads to Bilateral Alterations in Leg Dexterity.

    Science.gov (United States)

    Nagamori, Akira; Valero-Cuevas, Francisco J; Finley, James M

    2016-01-01

    Eccentric contractions can affect musculotendon mechanical properties and disrupt muscle proprioception, but their behavioral consequences are poorly understood. We tested whether repeated eccentric contractions of plantarflexor muscles of one leg affected the dexterity of either leg. Twenty healthy male subjects (27.3 ± 4.0 yrs) compressed a compliant and slender spring prone to buckling with each isolated leg. The maximal instability they could control (i.e., the maximal average sustained compression force, or lower extremity dexterity force, LED force ) quantified the dexterity of each leg. We found that eccentric contractions did not affect LED force , but reduced force variability (LED SD ). Surprisingly, LED force increased in the non-exposed, contralateral leg. These effects were specific to exposure to eccentric contractions because an effort-matched exposure to walking did not affect leg dexterity. In the exposed leg, eccentric contractions (i) reduced voluntary error corrections during spring compressions (i.e., reduced 0.5-4 Hz power of LED force ); (ii) did not change spinal excitability (i.e., unaffected H-reflexes); and (iii) changed the structure of the neural drive to the α-motoneuron pool (i.e., reduced EMG power within the 4-8 Hz physiological tremor band). These results suggest that repeated eccentric contractions alter the feedback control for dexterity in the exposed leg by reducing muscle spindle sensitivity. Moreover, the unexpected improvement in LED force in the non-exposed contralateral leg was likely a consequence of crossed-effects on its spinal and supraspinal feedback control. We discuss the implications of these bilateral effects of unilateral eccentric contractions, their effect on spinal and supraspinal control of dynamic foot-ground interactions, and their potential to facilitate rehabilitation from musculoskeletal and neuromotor impairments.

  9. Unilateral eccentric contraction of the plantarflexors leads to bilateral alterations in leg dexterity

    Directory of Open Access Journals (Sweden)

    Akira Nagamori

    2016-11-01

    Full Text Available Eccentric contractions can affect musculotendon mechanical properties and disrupt muscle proprioception, but their behavioral consequences are poorly understood. We tested whether repeated eccentric contractions of plantarflexor muscles of one leg affected the dexterity of either leg. Twenty healthy male subjects (27.3+/-4.0 yrs compressed a compliant and slender spring prone to buckling with each isolated leg. The maximal instability they could control (i.e., the maximal average sustained compression force, or lower extremity dexterity force, LEDForce quantified the dexterity of each leg. We found that eccentric contractions did not affect LEDForce, but reduced force variability (LEDSD. Surprisingly, LEDForce increased in the non-exposed, contralateral leg. These effects were specific to exposure to eccentric contractions because an effort-matched exposure to walking did not affect leg dexterity. In the exposed leg, eccentric contractions (i reduced voluntary error corrections during spring compressions (i.e., reduced 0.5-4 Hz power of LEDForce; (ii did not change spinal excitability (i.e., unaffected H-reflexes; and (iii changed the structure of the neural drive to the alpha-motoneuron pool (i.e., reduced EMG power within the 4-8 Hz physiological tremor band. These results suggest that repeated eccentric contractions alter the feedback control for dexterity in the exposed leg by reducing muscle spindle sensitivity. Moreover, the unexpected improvement in LEDForce in the non-exposed contralateral leg was likely a consequence of crossed-effects on its spinal and supraspinal feedback control. We discuss the implications of these bilateral effects of unilateral eccentric contractions, their effect on spinal and supraspinal control of dynamic foot-ground interactions, and their potential to facilitate rehabilitation from musculoskeletal and neuromotor impairments.

  10. Metaxin deficiency alters mitochondrial membrane permeability and leads to resistance to TNF-induced cell killing.

    Science.gov (United States)

    Ono, Koh; Wang, Xiaofei; Kim, Sung Ouk; Armstrong, Lucas C; Bornstein, Paul; Han, Jiahuai

    2010-02-01

    Metaxin, a mitochondrial outer membrane protein, is critical for TNF-induced cell death in L929 cells. Its deficiency, caused by retroviral insertion-mediated mutagenesis, renders L929 cells resistance to TNF killing. In this study, we further characterized metaxin deficiency-caused TNF resistance in parallel with Bcl-X(L) overexpression-mediated death resistance. We did not find obvious change in mitochondria membrane potential in metaxin-deficient (Met(mut)) and Bcl-X(L)-overexpressing cells, but we did find an increase in the release rate of the mitochondrial membrane potential probe rhodamine 123 (Rh123) that was preloaded into mitochondria. In addition, overexpression of a function-interfering mutant of metaxin (MetaΔTM/C) or Bcl-X(L) in MCF-7.3.28 cells also resulted in an acquired resistance to TNF killing and a faster rate of Rh123 release, indicating a close correlation between TNF resistance and higher rates of the dye release from the mitochondria. The release of Rh123 can be controlled by the mitochondrial membrane permeability transition (PT) pore, as targeting an inner membrane component of the PT pore by cyclosporin A (CsA) inhibited Rh123 release. However, metaxin deficiency and Bcl-X(L) overexpression apparently affect Rh123 release from a site(s) different from that of CsA, as CsA can overcome their effect. Though both metaxin and Bcl-X(L) appear to function on the outer mitochondrial membrane, they do not interact with each other. They may use different mechanisms to increase the permeability of Rh123, since previous studies have suggested that metaxin may influence certain outer membrane porins while Bcl-X(L) may form pores on the outer membrane. The alteration of the mitochondrial outer membrane properties by metaxin deficiency and Bcl-X(L) overexpression, as indicated by a quicker Rh123 release, may be helpful in maintaining mitochondrial integrity.

  11. Loss of Sonic hedgehog leads to alterations in intestinal secretory cell maturation and autophagy.

    Directory of Open Access Journals (Sweden)

    Jessica Gagné-Sansfaçon

    Full Text Available BACKGROUND: Intestinal epithelial cells express the Sonic and Indian hedgehog ligands. Despite the strong interest in gut hedgehog signaling in GI diseases, no studies have specifically addressed the singular role of intestinal epithelial cell Sonic hedgehog signaling. The aim of this study was to investigate the specific role of Sonic hedgehog in adult ileal epithelial homeostasis. METHODOLOGY/PRINCIPAL FINDINGS: A Sonic hedgehog intestinal epithelial conditional knockout mouse model was generated. Assessment of ileal histological abnormalities, crypt epithelial cell proliferation, epithelial cell fate, junctional proteins, signaling pathways, as well as ultrastructural analysis of intracellular organelles were performed in control and mutant mice. Mice lacking intestinal epithelial Sonic Hedgehog displayed decreased ileal crypt/villus length, decreased crypt proliferation as well as a decrease in the number of ileal mucin-secreting goblet cells and antimicrobial peptide-secreting Paneth cells during adult life. These secretory cells also exhibited disruption of their secretory products in mutant mice. Ultrastructural microscopy analysis revealed a dilated ER lumen in secretory cells. This phenotype was also associated with a decrease in autophagy. CONCLUSIONS/SIGNIFICANCE: Altogether, these findings indicate that the loss of Sonic hedgehog can lead to ileal secretory cell modifications indicative of endoplasmic reticulum stress, accompanied by a significant reduction in autophagy.

  12. Trypanosoma cruzi response to sterol biosynthesis inhibitors: morphophysiological alterations leading to cell death.

    Directory of Open Access Journals (Sweden)

    Rafael Luis Kessler

    Full Text Available The protozoan parasite Trypanosoma cruzi displays similarities to fungi in terms of its sterol lipid biosynthesis, as ergosterol and other 24-alkylated sterols are its principal endogenous sterols. The sterol pathway is thus a potential drug target for the treatment of Chagas disease. We describe here a comparative study of the growth inhibition, ultrastructural and physiological changes leading to the death of T. cruzi cells following treatment with the sterol biosynthesis inhibitors (SBIs ketoconazole and lovastatin. We first calculated the drug concentration inhibiting epimastigote growth by 50% (EC(50/72 h or killing all cells within 24 hours (EC(100/24 h. Incubation with inhibitors at the EC(50/72 h resulted in interesting morphological changes: intense proliferation of the inner mitochondrial membrane, which was corroborated by flow cytometry and confocal microscopy of the parasites stained with rhodamine 123, and strong swelling of the reservosomes, which was confirmed by acridine orange staining. These changes to the mitochondria and reservosomes may reflect the involvement of these organelles in ergosterol biosynthesis or the progressive autophagic process culminating in cell lysis after 6 to 7 days of treatment with SBIs at the EC(50/72 h. By contrast, treatment with SBIs at the EC(100/24 h resulted in rapid cell death with a necrotic phenotype: time-dependent cytosolic calcium overload, mitochondrial depolarization and reservosome membrane permeabilization (RMP, culminating in cell lysis after a few hours of drug exposure. We provide the first demonstration that RMP constitutes the "point of no return" in the cell death cascade, and propose a model for the necrotic cell death of T. cruzi. Thus, SBIs trigger cell death by different mechanisms, depending on the dose used, in T. cruzi. These findings shed new light on ergosterol biosynthesis and the mechanisms of programmed cell death in this ancient protozoan parasite.

  13. Lithium increases ammonium excretion leading to altered urinary acid-base buffer composition.

    Science.gov (United States)

    Trepiccione, Francesco; Altobelli, Claudia; Capasso, Giovambattista; Christensen, Birgitte Mønster; Frische, Sebastian

    2017-11-24

    Previous reports identify a voltage dependent distal renal tubular acidosis (dRTA) secondary to lithium (Li + ) salt administration. This was based on the inability of Li + -treated patients to increase the urine-blood (U-B) pCO 2 when challenged with NaHCO 3 and, the ability of sodium neutral phosphate or Na 2 SO 4 administration to restore U-B pCO 2 in experimental animal models. The underlying mechanisms for the Li + -induced dRTA are still unknown. To address this point, a 7 days time course of the urinary acid-base parameters was investigated in rats challenged with LiCl, LiCitrate, NaCl, or NaCitrate. LiCl induced the largest polyuria and a mild metabolic acidosis. Li + -treatment induced a biphasic response. In the first 2 days, proper urine volume and acidification occurred, while from the 3rd day of treatment, polyuria developed progressively. In this latter phase, the LiCl-treated group progressively excreted more NH 4 + and less pCO 2 , suggesting that NH 3 /NH 4 + became the main urinary buffer. This physiological parameter was corroborated by the upregulation of NBCn1 (a marker of increased ammonium recycling) in the inner stripe of outer medulla of LiCl treated rats. Finally, by investigating NH 4 + excretion in ENaC-cKO mice, a model resistant to Li + -induced polyuria, a primary role of the CD was confirmed. By definition, dRTA is characterized by deficient urinary ammonium excretion. Our data question the presence of a voltage-dependent Li + -induced dRTA in rats treated with LiCl for 7 days and the data suggest that the alkaline urine pH induced by NH 3 /NH 4 + as the main buffer has lead to the interpretation dRTA in previous studies.

  14. Alterations in growth, oxidative damage, and metal uptake of five aromatic rice cultivars under lead toxicity.

    Science.gov (United States)

    Ashraf, Umair; Hussain, Saddam; Anjum, Shakeel Ahmad; Abbas, Farhat; Tanveer, Mohsin; Noor, Mehmood Ali; Tang, Xiangru

    2017-06-01

    Lead (Pb) affects plant growth and its related physio-biochemical functions negatively. The present study investigated the responses of five different fragrant rice cultivars viz., Meixiangzhan (MXZ-2), Xiangyaxiangzhan (XYXZ), Guixiangzhan (GXZ), Basmati-385 (B-385), and Nongxiang-18 (NX-18) to four different Pb concentrations viz., 0, 400, 800 and 1200 μM. Results depicted that Pb toxicity significantly (P rice plants; nonetheless, a significant variation was found in the sensitivity of rice cultivars to Pb toxicity. Soluble sugars increased significantly only at 1200 μM in GXZ and 800 μM in B-385, whilst the maximum reductions in protein contents were observed at 1200 μM Pb for all rice cultivars. Proline contents were reduced for XYXZ and NX-18 at Pb1200 μM. Activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) as well as reduced glutathione (GSH) and oxidized glutathione (GSSG) showed differential behavior among Pb treatments and rice cultivars. Among rice cultivars, GXZ showed better antioxidative defense system under Pb toxicity compared with all other cultivars. For all rice cultivars, the trend for Pb accumulation was recorded as: roots > stems > leaves. Furthermore, significant but negative correlations among Pb uptake and plant height (r = -0.79), tillers per plant (r = -0.91) and plant dry biomass (r = -0.81) were recorded for all rice cultivars whereas the values of translocation factor (TF) from stems to leaves were higher than roots to stems. In sum, Pb reduced the early growth and caused physio-biochemical changes in all rice cultivars, nonetheless, GXZ proved better able to tolerate Pb stress than all other rice cultivars under study. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Altering the trajectory of early postnatal cortical development can lead to structural and behavioural features of autism

    Directory of Open Access Journals (Sweden)

    Chomiak Taylor

    2010-08-01

    Full Text Available Abstract Background Autism is a behaviourally defined neurodevelopmental disorder with unknown etiology. Recent studies in autistic children consistently point to neuropathological and functional abnormalities in the temporal association cortex (TeA and its associated structures. It has been proposed that the trajectory of postnatal development in these regions may undergo accelerated maturational alterations that predominantly affect sensory recognition and social interaction. Indeed, the temporal association regions that are important for sensory recognition and social interaction are one of the last regions to mature suggesting a potential vulnerability to early maturation. However, direct evaluation of the emerging hypothesis that an altered time course of early postnatal development can lead to an ASD phenotype remains lacking. Results We used electrophysiological, histological, and behavioural techniques to investigate if the known neuronal maturational promoter valproate, similar to that in culture systems, can influence the normal developmental trajectory of TeA in vivo. Brain sections obtained from postnatal rat pups treated with VPA in vivo revealed that almost 40% of cortical cells in TeA prematurely exhibited adult-like intrinsic electrophysiological properties and that this was often associated with gross cortical hypertrophy and a reduced predisposition for social play behaviour. Conclusions The co-manifestation of these functional, structural and behavioural features suggests that alteration of the developmental time course in certain high-order cortical networks may play an important role in the neurophysiological basis of autism.

  16. Catalogue of generic plant states leading to core melt in PWRs: includes appendix 1: detailed description of sequences leading to core melt

    International Nuclear Information System (INIS)

    1996-11-01

    The Task Group on thermal-hydraulic system behaviour was given a mandate from PWG 2 on Coolant System-Behaviour with the approval of CSNI to deal with the topic of Accident Management. A writing group was set up to identify generic plant states leading to core melt for pressurized water reactors (PWR) and find 'possible approaches to accident management measures' (AM-Measures) for dealing with them. From a matrix of 15 initiating events and 12 system failures (i.e. from 180 possibilities), 32 event sequences have been identified as leading to core melt. Each sequence has been divided into characteristic plant state intervals according to safety function challenges. For each of the 141 defined characteristic plant state intervals, the members of the Writing Group made proposals for AM-Measures

  17. Common Medications Which Lead to Unintended Alterations in Weight Gain or Organ Lipotoxicity.

    Science.gov (United States)

    Medici, Valentina; McClave, Stephen A; Miller, Keith R

    2016-01-01

    Obesity is one of the most common chronic conditions in the world. Its management is difficult, partly due to the multiple associated comorbidities including fatty liver, diabetes, hypertension, and hyperlipidemia. As a result, the choice of prescription medications in overweight and obese patients has important implications as some of them can actually worsen the fat accumulation and its associated metabolic complications. Several prescription medications are associated with weight gain with mechanisms that are often poorly understood and under-recognized. Even less data are available on the distribution of fat and lipotoxicity (the organ damage related to fat accumulation). The present review will discuss the drugs associated with weight gain, their mechanism of action, and the magnitude and timing of their effect.

  18. Including a service learning educational research project in a biology course-I: Assessing community awareness of childhood lead poisoning

    OpenAIRE

    Abu-Shakra, Amal; Saliim, Eric

    2012-01-01

    A university course project was developed and implemented in a biology course, focusing on environmental problems, to assess community awareness of childhood lead poisoning. A set of 385 questionnaires was generated and distributed in an urban community in North Carolina, USA. The completed questionnaires were sorted fırst into yes and no sets based on the responses obtained for the fırst question, which gauged the participants' awareness of lead as an indoor pollutant at 71% (n=273)...

  19. Correction of Hypothyroidism Leads to Change in Lean Body Mass without Altering Insulin Resistance.

    Science.gov (United States)

    Sirigiri, Sangeetha; Vaikkakara, Suresh; Sachan, Alok; Srinivasarao, P V L N; Epuri, Sunil; Anantarapu, Sailaja; Mukka, Arun; Chokkapu, Srinivasa Rao; Venkatanarasu, Ashok; Poojari, Ravi

    2016-12-01

    Hypothyroidism is associated with insulin resistance, dyslipidemia, and abnormal body composition. This study assessed changes in body composition and insulin resistance after thyroxine (T 4 ) replacement in overt hypothyroidism. In this prospective longitudinal study carried out in a tertiary care center, adult nondiabetic patients with overt hypothyroidism were rendered euthyroid on T 4 . Anthropometry including skinfold thickness (SFT) at the triceps and subscapularis was recorded. Patients underwent testing for fasting plasma glucose, creatinine, serum insulin, T 4 , thyrotropin (TSH) and body composition analysis by dual-energy X-ray absorptiometry (DEXA) both before and at 2 months after restoration to the euthyroid state. Twenty-seven patients (20 female and 7 male) aged 35.3 ± 11.0 years (min-max: 17-59 years) with overt hypothyroidism were recruited. Serum T 4 at the time of recruitment was 48.9 ± 24.6 nmol/l (normal range = 64.4-142 nmol/l). All patients had TSH ≥50 µIU/l. Following treatment, there was a mean body weight reduction of 1.7 kg (p = 0.01). Waist circumference as well as triceps and subscapularis SFT decreased significantly (p change in fat mass (FM), percentage of fat (%FM) or bone mineral content in any of the specified regions or in the body as a whole. In contrast, mean lean body mass (LBM) decreased significantly by 0.8 kg (p resistance and level of glycemia were not affected by treatment with T 4 . LBM decreases significantly without affecting FM after correction of hypothyroidism. Insulin resistance was not influenced by T 4 treatment.

  20. Trpm4 gene invalidation leads to cardiac hypertrophy and electrophysiological alterations.

    Directory of Open Access Journals (Sweden)

    Marie Demion

    Full Text Available RATIONALE: TRPM4 is a non-selective Ca2+-activated cation channel expressed in the heart, particularly in the atria or conduction tissue. Mutations in the Trpm4 gene were recently associated with several human conduction disorders such as Brugada syndrome. TRPM4 channel has also been implicated at the ventricular level, in inotropism or in arrhythmia genesis due to stresses such as ß-adrenergic stimulation, ischemia-reperfusion, and hypoxia re-oxygenation. However, the physiological role of the TRPM4 channel in the healthy heart remains unclear. OBJECTIVES: We aimed to investigate the role of the TRPM4 channel on whole cardiac function with a Trpm4 gene knock-out mouse (Trpm4-/- model. METHODS AND RESULTS: Morpho-functional analysis revealed left ventricular (LV eccentric hypertrophy in Trpm4-/- mice, with an increase in both wall thickness and chamber size in the adult mouse (aged 32 weeks when compared to Trpm4+/+ littermate controls. Immunofluorescence on frozen heart cryosections and qPCR analysis showed no fibrosis or cellular hypertrophy. Instead, cardiomyocytes in Trpm4-/- mice were smaller than Trpm4+/+with a higher density. Immunofluorescent labeling for phospho-histone H3, a mitosis marker, showed that the number of mitotic myocytes was increased 3-fold in the Trpm4-/-neonatal stage, suggesting hyperplasia. Adult Trpm4-/- mice presented multilevel conduction blocks, as attested by PR and QRS lengthening in surface ECGs and confirmed by intracardiac exploration. Trpm4-/-mice also exhibited Luciani-Wenckebach atrioventricular blocks, which were reduced following atropine infusion, suggesting paroxysmal parasympathetic overdrive. In addition, Trpm4-/- mice exhibited shorter action potentials in atrial cells. This shortening was unrelated to modifications of the voltage-gated Ca2+ or K+ currents involved in the repolarizing phase. CONCLUSIONS: TRPM4 has pleiotropic roles in the heart, including the regulation of conduction and cellular

  1. Neuroinflammation leads to region-dependent alterations in astrocyte gap junction communication and hemichannel activity.

    Science.gov (United States)

    Karpuk, Nikolay; Burkovetskaya, Maria; Fritz, Teresa; Angle, Amanda; Kielian, Tammy

    2011-01-12

    Inflammation attenuates gap junction (GJ) communication in cultured astrocytes. Here we used a well-characterized model of experimental brain abscess as a tool to query effects of the CNS inflammatory milieu on astrocyte GJ communication and electrophysiological properties. Whole-cell patch-clamp recordings were performed on green fluorescent protein (GFP)-positive astrocytes in acute brain slices from glial fibrillary acidic protein-GFP mice at 3 or 7 d after Staphylococcus aureus infection in the striatum. Astrocyte GJ communication was significantly attenuated in regions immediately surrounding the abscess margins and progressively increased to levels typical of uninfected brain with increasing distance from the abscess proper. Conversely, astrocytes bordering the abscess demonstrated hemichannel activity as evident by enhanced ethidium bromide (EtBr) uptake that could be blocked by several pharmacological inhibitors, including the connexin 43 (Cx43) mimetic peptide Gap26, carbenoxolone, the pannexin1 (Panx1) mimetic peptide (10)Panx1, and probenecid. However, hemichannel opening was transient with astrocytic EtBr uptake observed near the abscess at day 3 but not day 7 after infection. The region-dependent pattern of hemichannel activity at day 3 directly correlated with increases in Cx43, Cx30, Panx1, and glutamate transporter expression (glial L-glutamate transporter and L-glutamate/L-aspartate transporter) along the abscess margins. Changes in astrocyte resting membrane potential and input conductance correlated with the observed changes in GJ communication and hemichannel activity. Collectively, these findings indicate that astrocyte coupling and electrical properties are most dramatically affected near the primary inflammatory site and reveal an opposing relationship between the open states of GJ channels versus hemichannels during acute infection. This relationship may extend to other CNS diseases typified with an inflammatory component.

  2. Effects of curcumin and tannic acid on the aluminum- and lead-induced oxidative neurotoxicity and alterations in NMDA receptors.

    Science.gov (United States)

    Tüzmen, Münire Nalan; Yücel, Nilgün Candan; Kalburcu, Tülden; Demiryas, Nazan

    2015-02-01

    Exposure to aluminum (Al) and lead (Pb) can cause brain damage. Also, Pb and Al exposure alters N-methyl-d-aspartate receptor (NMDAR) subunit expression. Polyphenols such as tannic acid and curcumin are very efficient chelator for metals. The effects of curcumin and tannic acid (polyphenols) on Al(3+)- and Pb(2+)-induced oxidative stress were examined by investigating lipid peroxidation (LPO) levels, antioxidant enzyme activities, acetyl cholinesterase (AChE) activity and also NMDA receptor subunits 2A and 2B concentrations in the brain tissue of rats sub-chronically. Rats were divided into seven groups as control, Al, Pb, aluminum-tannic acid treatment (AlT), aluminum-curcumin treatment (AlC), lead-tannic acid treatment (PbT) and lead-curcumin treatment (PbC). After 16 weeks of treatment, LPO levels in the brain and hippocampus were higher in Al(3+)-exposed rats than that of Pb(2+)-exposed group. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in brain tissue of Al- and Pb-exposed rats increased significantly compared with control, while catalase (CAT) and AChE activities decreased. It was observed that metal exposure affected NR2A concentrations more than NR2B concentrations and also that polyphenol treatments increased these receptor protein concentrations.

  3. Including a Service Learning Educational Research Project in a Biology Course-I: Assessing Community Awareness of Childhood Lead Poisoning

    Science.gov (United States)

    Abu-Shakra, Amal; Saliim, Eric

    2012-01-01

    A university course project was developed and implemented in a biology course, focusing on environmental problems, to assess community awareness of childhood lead poisoning. A set of 385 questionnaires was generated and distributed in an urban community in North Carolina, USA. The completed questionnaires were sorted first into yes and no sets…

  4. Altered control strategy between leading and trailing leg increases knee adduction moment in the elderly while descending stairs.

    Science.gov (United States)

    Karamanidis, Kiros; Arampatzis, Adamantios

    2011-02-24

    The aim of the study was to examine the external knee adduction moments in a group of older and younger adults while descending stairs and thus the possibility of an increased risk of knee osteoarthritis due to altered knee joint loading in the elderly. Twenty-seven older and 16 younger adults descended a purpose-built staircase. A motion capture system and a force plate were used to determine the subjects' 3D kinematics and ground reaction forces (GRF) during locomotion. Calculation of the leg kinematics and kinetics was done by means of a rigid, three-segment, 3D leg model. In the initial portion of the support phase, older adults showed a more medio-posterior GRF vector relative to the ankle joint, leading to lower ankle joint moments (Pelderly (Pcontrol strategy while stepping down is a more medially directed GRF vector increasing the magnitude of external knee adduction moment in the elderly. The observed changes between leading and trailing leg in the elderly may cause a redistribution of the mechanical load at the tibiofemoral joint, affecting the initiation and progression of knee osteoarthritis in the elderly. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Respiratory alkalosis may impair the production of vitamin D and lead to significant morbidity, including the fibromyalgia syndrome.

    Science.gov (United States)

    Lewis, John M; Fontrier, Toinette H; Coley, J Lynn

    2017-05-01

    Hyperventilation caused by physical and/or psychological stress may lead to significant respiratory alkalosis and an elevated systemic pH. The alkalotic pH may in turn suppress the normal renal release of phosphate into the urine, thereby interrupting the endogenous production of 1,25-dihydroxyvitamin D (calcitriol). This could cause a shortfall in its normal production, leading to a variety of adverse consequences. It might partially explain the pathogenesis of acute mountain sickness, a treatable disease characterized by severe hyperventilation secondary to the hypoxia of high altitude exposure. Milder degrees of hyperventilation due to different forms of stress may produce other conditions which share characteristics with acute mountain sickness. One of these may be the fibromyalgia syndrome, a chronic painful disorder for which no satisfactory treatment exists. Should fibromyalgia and acute mountain sickness have a common etiology, may they also share a common form of treatment? Evidence is presented to support this hypothesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Modeling the Nonlinear, Strain Rate Dependent Deformation of Shuttle Leading Edge Materials with Hydrostatic Stress Effects Included

    Science.gov (United States)

    Goldberg, Robert K.; Carney, Kelly S.

    2004-01-01

    An analysis method based on a deformation (as opposed to damage) approach has been developed to model the strain rate dependent, nonlinear deformation of woven ceramic matrix composites, such as the Reinforced Carbon Carbon (RCC) material used on the leading edges of the Space Shuttle. In the developed model, the differences in the tension and compression deformation behaviors have also been accounted for. State variable viscoplastic equations originally developed for metals have been modified to analyze the ceramic matrix composites. To account for the tension/compression asymmetry in the material, the effective stress and effective inelastic strain definitions have been modified. The equations have also been modified to account for the fact that in an orthotropic composite the in-plane shear response is independent of the stiffness in the normal directions. The developed equations have been implemented into LS-DYNA through the use of user defined subroutines (UMATs). Several sample qualitative calculations have been conducted, which demonstrate the ability of the model to qualitatively capture the features of the deformation response present in woven ceramic matrix composites.

  7. Perinatal Lead Exposure Alters Gut Microbiota Composition and Results in Sex-specific Bodyweight Increases in Adult Mice.

    Science.gov (United States)

    Wu, Jianfeng; Wen, Xiaoquan William; Faulk, Christopher; Boehnke, Kevin; Zhang, Huapeng; Dolinoy, Dana C; Xi, Chuanwu

    2016-06-01

    Heavy metal pollution is a principle source of environmental contamination. Epidemiological and animal data suggest that early life lead (Pb) exposure results in critical effects on epigenetic gene regulation and child and adult weight trajectories. Using a mouse model of human-relevant exposure, we investigated the effects of perinatal Pb exposure on gut microbiota in adult mice, and the link between gut microbiota and bodyweight changes. Following Pb exposure during gestation and lactation via maternal drinking water, bodyweight in A(vy) strain wild-type non-agouti (a/a) offspring was tracked through adulthood. Gut microbiota of adult mice were characterized by deep DNA sequencing of bacterial 16S ribosomal RNA genes. Data analyses were stratified by sex and adjusted for litter effects. A Bayesian variable selection algorithm was used to analyze associations between bacterial operational taxonomic units and offspring adult bodyweight. Perinatal Pb exposure was associated with increased adult bodyweight in male (P compositions were significantly different (analysis of molecular variance, P gut microbiota were highly associated with adult bodyweight (P = .028; effect size = 2.59). Thus, perinatal Pb exposure results in altered adult gut microbiota regardless of sex, and these changes are highly correlated with increased bodyweight in males. Adult gut microbiota can be shaped by early exposures and may contribute to disease risks in a sex-specific manner. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Cadmium induced ROS alters M1 and M3 receptors, leading to SN56 cholinergic neuronal loss, through AChE variants disruption.

    Science.gov (United States)

    Moyano, Paula; de Frias, Mariano; Lobo, Margarita; Anadon, María José; Sola, Emma; Pelayo, Adela; Díaz, María Jesús; Frejo, María Teresa; Del Pino, Javier

    2018-02-01

    Cadmium, an environmental neurotoxic compound, produces cognitive disorders, although the mechanism remains unknown. Previously, we described that cadmium induces a more pronounced cell death on cholinergic neurons from basal forebrain (BF). This effect, partially mediated by M1 receptor blockade, triggering it through AChE splices variants alteration, may explain cadmium effects on learning and memory processes. Cadmium has been also reported to induce oxidative stress generation leading to M2 and M4 muscarinic receptors alteration, in hippocampus and frontal cortex, which are necessary to maintain cell viability and cognitive regulation, so their alteration in BF could also mediate this effect. Moreover, it has been reported that antioxidant treatment could reverse cognitive disorders, muscarinic receptor and AChE variants alterations induced by cadmium. Thus, we hypothesized that cadmium induced cell death of BF cholinergic neurons is mediated by oxidative stress generation and this mechanism could produce this effect, in part, through AChE variants altered by muscarinic receptors disruption. To prove this, we evaluated in BF SN56 cholinergic neurons, whether cadmium induces oxidative stress and alters muscarinic receptors, and their involvement in the induction of cell death through alteration of AChE variants. Our results show that cadmium induces oxidative stress, which mediates partially the alteration of AChE variants and M2 to M4 muscarinic receptors expression and blockage of M1 receptor. In addition, cadmium induced oxidative stress generation by M1 and M3 receptors alteration through AChE variants disruption, leading to cell death. These results provide new understanding of the mechanisms contributing to cadmium harmful effects on cholinergic neurons. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response.

    Science.gov (United States)

    Khan, Mike; Harms, Jerome S; Marim, Fernanda M; Armon, Leah; Hall, Cherisse L; Liu, Yi-Ping; Banai, Menachem; Oliveira, Sergio C; Splitter, Gary A; Smith, Judith A

    2016-12-01

    Brucella species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how Brucella spp. succeed in sabotaging immune host cells and how Brucella spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in Brucella physiology and in shaping host-Brucella interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a ΔbpdA phosphodiesterase mutant producing excess c-di-GMP displays marked attenuation in vitro and in vivo during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the ΔbpdA mutant induced a weaker host immune response than did wild-type Brucella or the low-c-di-GMP guanylate cyclase ΔcgsB mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, ΔbpdA mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing Brucella to successfully navigate stressful and shifting environments to establish intracellular infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. Inhibition of the αvβ6 integrin leads to limited alteration of TGF-α-induced pulmonary fibrosis

    Science.gov (United States)

    Madala, Satish K.; Korfhagen, Thomas R.; Schmidt, Stephanie; Davidson, Cynthia; Edukulla, Ramakrishna; Ikegami, Machiko; Violette, Shelia M.; Weinreb, Paul H.; Sheppard, Dean

    2014-01-01

    A number of growth factors and signaling pathways regulate matrix deposition and fibroblast proliferation in the lung. The epidermal growth factor receptor (EGFR) family of receptors and the transforming growth factor-β (TGF-β) family are active in diverse biological processes and are central mediators in the initiation and maintenance of fibrosis in many diseases. Transforming growth factor-α (TGF-α) is a ligand for the EGFR, and doxycycline (Dox)-inducible transgenic mice conditionally expressing TGF-α specifically in the lung epithelium develop progressive fibrosis accompanied with cachexia, changes in lung mechanics, and marked pleural thickening. Although recent studies demonstrate that EGFR activation modulates the fibroproliferative effects involved in the pathogenesis of TGF-β induced pulmonary fibrosis, in converse, the direct role of EGFR induction of the TGF-β pathway in the lung is unknown. The αvβ6 integrin is an important in vivo activator of TGF-β activation in the lung. Immunohistochemical analysis of αvβ6 protein expression and bronchoalveolar analysis of TGF-β pathway signaling indicates activation of the αvβ6/TGF-β pathway only at later time points after lung fibrosis was already established in the TGF-α model. To determine the contribution of the αvβ6/TGF-β pathway on the progression of established fibrotic disease, TGF-α transgenic mice were administered Dox for 4 wk, which leads to extensive fibrosis; these mice were then treated with a function-blocking anti-αvβ6 antibody with continued administration of Dox for an additional 4 wk. Compared with TGF-α transgenic mice treated with control antibody, αvβ6 inhibition significantly attenuated pleural thickening and altered the decline in lung mechanics. To test the effects of genetic loss of the β6 integrin, TGF-α transgenic mice were mated with β6-null mice and the degree of fibrosis was compared in adult mice following 8 wk of Dox administration. Genetic ablation of

  11. The influence of environmental exposure to complex mixtures including PAHs and lead on genotoxic effects in children living in Upper Silesia, Poland

    DEFF Research Database (Denmark)

    Mielzynska, Danuta; Siwinska, Ewa; Kapka, Lucyna

    2006-01-01

    Environmental exposure is a complex mixture of hazardous compounds with different mechanisms of toxicity. In case of concomitant exposure to carcinogenic substances--such as polycyclic aromatic hydrocarbons (PAHs)--and to heavy metals--such as lead (Pb)--the level of DNA damage may be enhanced...... and to investigate their relation with the environmental exposure to PAHs and Pb. The examined population included 74 children 5-14-year-old who lived in two cities located in the most polluted centre of the Silesia province. Individual exposure to lead was assessed for each child by measuring lead in blood (Pb....... Emissions from coal-burning stoves are important contributors to the total exposure to PAHs and Pb in Silesian children....

  12. Regional alterations of brain biogenic amines and GABA/glutamate levels in rats following chronic lead exposure during neonatal development

    Energy Technology Data Exchange (ETDEWEB)

    Shailesh Kumar, M.V.; Desiraju, T. (National Inst. of Mental Health and Neuro Sciences, Bangalore (India). Dept. of Neurophysiology)

    1990-06-01

    Wistar rat pups were administered either a high dose of lead acetate (400 {mu}g lead-g body weight/day) or a low dose (100 {mu}g lead/g body weight/day) by gastric intubation, from 2 days through 60 days of age. The rats on both these doses exhibited statistically significant decreases in body and brain weights throughout the lead treatment period. A group of rats on high dose was also rehabilitated by discontinuing the lead from 60 days of age. In these rats, at 160 days of age, the body weight but not the brain weight recovered to normal levels. During the lead intake, the rats on high dose revealed significant elevations in the levels of noradrenaline (NA) in the hippocampus (HI), cerebellum (CE), hypothalamus (HY), brainstem (BS), and accumbens-striatum (SA). The elevated levels in all the above regions except in the HY persisted even after rehabilitation. The dopamine (DA) levels changed significantly in opposite directions in HY (elevation) and BS (reduction) during the lead treatment, and the HY recovered after rehabilitation. Under lead, the serotonin (5HT) levels were elevated significantly in the HI, BS and MC (motor cortex), while after rehabilitation the abnormality persisted only in the MC. Low dose lead treatment was also effective on the same areas of brain. In the low dose group, estimation of the levels of GABA and glutamate were also done, and a significant decrease of GABA in CE and glutamate in MC was observed. The differences observed in the neurotoxic effects (none or significant) of lead in the different regions for each of the transmitters (NA, DA, 5HT) supports the interesting conclusion that the vulnerability of the axon terminals of any given type is dependent on some regional factors, although the projections of the different regions originate from an apparently similar category of neurons in the brain stem. (orig.).

  13. Increased Incidence and Altered Risk Demographics of Childhood Lead Poisoning: Predicting the Impacts of the CDC’s 5 µg/dL Reference Value in Massachusetts (USA)

    Science.gov (United States)

    Handler, Phoebe; Brabander, Daniel

    2012-01-01

    In May 2012, the CDC adopted a new sliding scale reference value for childhood lead poisoning, reducing the former 10 µg/dL benchmark by half. Using Massachusetts (MA) as a model state, we estimated the change in the population of 9–47 month-olds at risk for lead poisoning. We then examined the impact of the 5 µg/dL reference value on the demographic characteristics of lead risk in MA communities. We find that the new CDC benchmark will lead to a 1470% increase in childhood lead poisoning cases among 9–47 month-olds in MA, with nearly 50% of the examined communities experiencing an increased prevalence of lead poisoning. Further, the top 10 MA communities with BLLs ≥5 µg/dL have significantly fewer foreign-born residents and significantly larger white populations than the highest risk communities formerly identified by the MA Childhood Lead Poisoning Prevention Program. The CDC’s new 5 µg/dL lead poisoning benchmark will drastically increase the number of children with elevated BLLs and alter the distribution and demographics high-risk communities in MA. PMID:23202824

  14. Fear conditioning leads to alteration in specific genes expression in cortical and thalamic neurons that project to the lateral amygdala.

    Science.gov (United States)

    Katz, Ira K; Lamprecht, Raphael

    2015-02-01

    RNA transcription is needed for memory formation. However, the ability to identify genes whose expression is altered by learning is greatly impaired because of methodological difficulties in profiling gene expression in specific neurons involved in memory formation. Here, we report a novel approach to monitor the expression of genes after learning in neurons in specific brain pathways needed for memory formation. In this study, we aimed to monitor gene expression after fear learning. We retrogradely labeled discrete thalamic neurons that project to the lateral amygdala (LA) of rats. The labeled neurons were dissected, using laser microdissection microscopy, after fear conditioning learning or unpaired training. The RNAs from the dissected neurons were subjected to microarray analysis. The levels of selected RNAs detected by the microarray analysis to be altered by fear conditioning were also assessed by nanostring analysis. We observed that the expression of genes involved in the regulation of translation, maturation and degradation of proteins was increased 6 h after fear conditioning compared to unpaired or naïve trained rats. These genes were not expressed 24 h after training or in cortical neurons that project to the LA. The expression of genes involved in transcription regulation and neuronal development was altered after fear conditioning learning in the cortical-LA pathway. The present study provides key information on the identity of genes expressed in discrete thalamic and cortical neurons that project to the LA after fear conditioning. Such an approach could also serve to identify gene products as targets for the development of a new generation of therapeutic agents that could be aimed to functionally identified brain circuits to treat memory-related disorders. © 2014 International Society for Neurochemistry.

  15. Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model

    Directory of Open Access Journals (Sweden)

    Danielle Botelho

    2018-03-01

    Full Text Available Here we examine the organ level toxicology of both carbon black (CB and silver nanoparticles (AgNP. We aim to determine metal-specific effects to respiratory function, inflammation and potential interactions with lung lining fluid (LLF. C57Bl6/J male mice were intratracheally instilled with saline (control, low (0.05 μg/g or high (0.5 μg/g doses of either AgNP or CB 15 nm nanospheres. Lung histology, cytology, surfactant composition and function, inflammatory gene expression, and pulmonary function were measured at 1, 3, and 7 days post-exposure. Acutely, high dose CB resulted in an inflammatory response, increased neutrophilia and cytokine production, without alteration in surfactant composition or respiratory mechanics. Low dose CB had no effect. Neither low nor high dose AgNPs resulted in an acute inflammatory response, but there was an increase in work of breathing. Three days post-exposure with CB, a persistent neutrophilia was noted. High dose AgNP resulted in an elevated number of macrophages and invasion of lymphocytes. Additionally, AgNP treated mice displayed increased expression of IL1B, IL6, CCL2, and IL10. However, there were no significant changes in respiratory mechanics. At day 7, inflammation had resolved in AgNP-treated mice, but tissue stiffness and resistance were significantly decreased, which was accompanied by an increase in surfactant protein D (SP-D content. These data demonstrate that the presence of metal alters the response of the lung to nanoparticle exposure. AgNP-surfactant interactions may alter respiratory function and result in a delayed immune response, potentially due to modified airway epithelial cell function.

  16. Effects of lead nitrate on histo-cytological alterations of corpuscles of Stannius of stinging catfish, Heteropneustes fossilis

    Directory of Open Access Journals (Sweden)

    Rubi Rai

    2016-07-01

    Full Text Available Background: The present study investigated the effects of lead nitrate on the histo-cytological changes in the corpuscles of Stannius (CS of Heteropneustes fossilis. Methods: Catfish, Heteropneustes fossilis were subjected to 657.6 mg/L and 164.4 mg/L of lead nitrate for 96 h and 28 days, respectively. Blood from fish was collected on 24, 48, 72 and 96 h in short-term and after 7, 14, 21, and 28 days in long-term experiment. Blood was collected for analysis of calcium levels and CS were fixed for histological studies. Results: Plasma calcium levels of the fish remain unaffected at 24 h. The levels decrease after 48 h which persists till 96 h. Plasma calcium levels of the fish exposed to lead for 7 days exhibit a decrease which persists progressively till 28 days. After 96 h, AF-positive cells of CS exhibit increased granulation. No change in the nuclear volume of these cells has been noticed. An increased nuclear volume has been recorded in the AF-negative cells of CS of 96 h lead exposed fish. After 14 days, the nuclear volume of AF-positive cells decreases. Heavy accumulation of secretory granules and decrease in the nuclear volume of AF-positive cells have been recorded after 21 days which pronounced after 28 days. Moreover, few degenerating cells have also been encountered. AF-negative cells of CS exhibit an increase in the nuclear volume after 21 and 28 days lead treatment. Conclusion: Present findings suggest that exposure of the lead to catfish Heteropneustes fossilis caused CS inactivity .

  17. Determination of point isotropic buildup factors of gamma rays including incoherent and coherent scattering for aluminum, iron, lead, and water by discrete ordinates method

    International Nuclear Information System (INIS)

    Kitsos, S.; Assad, A.; Diop, C.M.; Nimal, J.C.

    1994-01-01

    Exposure and energy absorption buildup factors for aluminum, iron, lead, and water are calculated by the SNID discrete ordinates code for an isotropic point source in a homogeneous medium. The calculation of the buildup factors takes into account the effects of both bound-electron Compton (incoherent) and coherent (Rayleigh) scattering. A comparison with buildup factors from the literature shows that these two effects greatly increase the buildup factors for energies below a few hundred kilo-electron-volts, and thus the new results are improved relative to the experiment. This greater accuracy is due to the increase in the linear attenuation coefficient, which leads to the calculation of the buildup factors for a mean free path with a smaller shield thickness. On the other hand, for the same shield thickness, exposure increases when only incoherent scattering is included and decreases when only coherent scattering is included, so that the exposure finally decreases when both effects are included. Great care must also be taken when checking the approximations for gamma-ray deep-penetration transport calculations, as well as for the cross-section treatment and origin

  18. Altered Tau Isoform Ratio Caused by Loss of FUS and SFPQ Function Leads to FTLD-like Phenotypes

    Directory of Open Access Journals (Sweden)

    Shinsuke Ishigaki

    2017-01-01

    Full Text Available Fused in sarcoma (FUS and splicing factor, proline- and glutamine-rich (SFPQ are RNA binding proteins that regulate RNA metabolism. We found that alternative splicing of the Mapt gene at exon 10, which generates 4-repeat tau (4R-T and 3-repeat tau (3R-T, is regulated by interactions between FUS and SFPQ in the nuclei of neurons. Hippocampus-specific FUS- or SFPQ-knockdown mice exhibit frontotemporal lobar degeneration (FTLD-like behaviors, reduced adult neurogenesis, accumulation of phosphorylated tau, and hippocampal atrophy with neuronal loss through an increased 4R-T/3R-T ratio. Normalization of this increased ratio by 4R-T-specific silencing results in recovery of the normal phenotype. These findings suggest a biological link among FUS/SFPQ, tau isoform alteration, and phenotypic expression, which may function in the early pathomechanism of FTLD.

  19. Lead induces DNA damage and alteration of ALAD and antioxidant genes mRNA expression in construction site workers.

    Science.gov (United States)

    Akram, Zertashia; Riaz, Sadaf; Kayani, Mahmood Akhtar; Jahan, Sarwat; Ahmad, Malik Waqar; Ullah, Muhammad Abaid; Wazir, Hizbullah; Mahjabeen, Ishrat

    2018-01-16

    Oxidative stress and DNA damage are considered as possible mechanisms involved in lead toxicity. To test this hypothesis, DNA damage and expression variations of aminolevulinic acid dehydratase (ALAD), superoxide dismutase 2 (SOD2), and 8-oxoguanine DNA glycosylase 2a (OGG1-2a) genes was studied in a cohort of 100 exposed workers and 100 controls with comet assay and real-time polymerse chain reaction (PCR). Results indicated that increased number of comets was observed in exposed workers versus controls (p < 0.001). After qPCR analysis, significant down-regulation in ALAD (p < 0.0001), SOD2 (p < 0.0001), and OGG1-2a (p < 0.0001) level was observed in exposed workers versus controls. Additionally, a positive spearmen correlation was observed between ALAD versus SOD2 (r = 0.402**, p < 0.001), ALAD versus OGG1-2a (r = 0.235*, p < 0.05), and SOD2 versus OGG1-2a (r = 0.292*, p < 0.05). This study showed that lead exposure induces DNA damage, which is accompanied by an elevated intensity of oxidative stress and expression variation of lead-related gene.

  20. Postnatal protein malnutrition induces neurochemical alterations leading to behavioral deficits in rats: prevention by selenium or zinc supplementation.

    Science.gov (United States)

    Adebayo, Olusegun L; Adenuga, Gbenga A; Sandhir, Rajat

    2014-11-01

    Protein malnutrition (PM) is a worldwide problem affecting brain development in a large number of children. The present study was aimed at studying the perturbations in antioxidant defense system resulting from protein deficiency and to evaluate the preventive effect of Se and Zn on cortex and cerebellum. Well-fed (WF) and PM rats were fed on 16 and 5% protein diet, respectively. After 10 weeks, animals were supplemented with Se and Zn at a concentration of 0.15 and 227 mg/l in drinking water for 3 weeks. PM rats showed significant increase in lipid peroxidation, nitrite, and protein carbonyl levels. Reduction in the activity of antioxidant enzymes, thiol levels, GSH/GSSG ratio, and neurobehavioral deficits were observed in PM groups. Se and Zn supplementation reduced the levels of lipid peroxidation, nitrite, and protein carbonyl and restored the activity of antioxidant enzymes and thiol levels in the cortex and cerebellum of PM rats along with neurobehavioral deficits. The study showed that Se and Zn supplementation might be beneficial in preventing biochemical alterations and neurobehavioral deficits in PM children.

  1. Chronic alterations in growth hormone/insulin-like growth factor-I signaling lead to changes in mouse tendon structure

    DEFF Research Database (Denmark)

    Nielsen, R H; Clausen, N M; Schjerling, P

    2014-01-01

    RNA expression (targets: GAPDH, RPLP0, IGF-IEa, IGF-IR, COL1A1, COL3A1, TGF-β1, TGF-β2, TGF-β3, versican, scleraxis, tenascin C, fibronectin, fibromodulin, decorin) in the Achilles tendon, and the mRNA expression was also measured in calf muscle (same targets as tendon plus IGF-IEb, IGF-IEc). We found that GHR......The growth hormone/insulin-like growth factor-I (GH/IGF-I) axis is an important stimulator of collagen synthesis in connective tissue, but the effect of chronically altered GH/IGF-I levels on connective tissue of the muscle-tendon unit is not known. We studied three groups of mice; 1) giant......-/- mice had significantly lower collagen fibril volume fraction in Achilles tendon, as well as decreased mRNA expression of IGF-I isoforms and collagen types I and III in muscle compared to CTRL. In contrast, the mRNA expression of IGF-I isoforms and collagens in bGH mice was generally high in both tendon...

  2. Obese fathers lead to an altered metabolism and obesity in their children in adulthood: review of experimental and human studies

    Directory of Open Access Journals (Sweden)

    Fernanda Ornellas

    Full Text Available Abstract Objective: To discuss the recent literature on paternal obesity, focusing on the possible mechanisms of transmission of the phenotypes from the father to the children. Sources: A non-systematic review in the PubMed database found few publications in which paternal obesity was implicated in the adverse transmission of characteristics to offspring. Specific articles on epigenetics were also evaluated. As the subject is recent and still controversial, all articles were considered regardless of year of publication. Summary of findings: Studies in humans and animals have established that paternal obesity impairs their hormones, metabolism, and sperm function, which can be transmitted to their offspring. In humans, paternal obesity results in insulin resistance/type 2 diabetes and increased levels of cortisol in umbilical cord blood, which increases the risk factors for cardiovascular disease. Notably, there is an association between body fat in parents and the prevalence of obesity in their daughters. In animals, paternal obesity led to offspring alterations on glucose-insulin homeostasis, hepatic lipogenesis, hypothalamus/feeding behavior, kidney of the offspring; it also impairs the reproductive potential of male offspring with sperm oxidative stress and mitochondrial dysfunction. An explanation for these observations (human and animal is epigenetics, considered the primary tool for the transmission of phenotypes from the father to offspring, such as DNA methylation, histone modifications, and non-coding RNA. Conclusions: Paternal obesity can induce programmed phenotypes in offspring through epigenetics. Therefore, it can be considered a public health problem, affecting the children's future life.

  3. In-Person Communication Between Radiologists and Acute Care Surgeons Leads to Significant Alterations in Surgical Decision Making.

    Science.gov (United States)

    Dickerson, Elliot C; Alam, Hasan B; Brown, Richard K J; Stojanovska, Jadranka; Davenport, Matthew S

    2016-08-01

    The aim of this study was to determine if direct in-person communication between an acute care surgical team and radiologists alters surgical decision making. Informed consent was waived for this institutional review board-exempt, HIPAA-compliant, prospective quality improvement study. From January 29, 2015 to December 10, 2015, semiweekly rounds lasting approximately 60 min were held between the on-call acute care surgery team (attending surgeon, chief resident, and residents) and one of three expert abdominal radiologists. A comprehensive imaging review was performed of recent and comparison examinations for cases selected by the surgeons in which medical and/or surgical decision making was pending. All reviewed examinations had available finalized reports known to the surgical team. RADPEER interradiologist concordance scores were assigned to all reviewed examinations. The impression and plan of the attending surgeon were recorded before and after each in-person review. One hundred patients were reviewed with 11 attending surgeons. The in-person meetings led to changes in surgeons' diagnostic impressions in 43% (43 of 100) and changes in medical and/or surgical planning in 43% (43 of 100; 20 acute changes, 23 nonacute changes, 19 changes in operative management) of cases. There were major discrepancies (RADPEER score ≥3) between the impression of the reviewing radiologist and the written report in 11% of cases (11 of 100). Targeted in-person collaboration between radiologists and acute care surgeons is associated with substantial and frequent changes in patient management, even when the original written report contains all necessary data. The primary mechanism seems to be promotion of a shared mental model that facilitates the exchange of complex information. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  4. Obese fathers lead to an altered metabolism and obesity in their children in adulthood: review of experimental and human studies.

    Science.gov (United States)

    Ornellas, Fernanda; Carapeto, Priscila V; Mandarim-de-Lacerda, Carlos A; Aguila, Marcia B

    To discuss the recent literature on paternal obesity, focusing on the possible mechanisms of transmission of the phenotypes from the father to the children. A non-systematic review in the PubMed database found few publications in which paternal obesity was implicated in the adverse transmission of characteristics to offspring. Specific articles on epigenetics were also evaluated. As the subject is recent and still controversial, all articles were considered regardless of year of publication. Studies in humans and animals have established that paternal obesity impairs their hormones, metabolism, and sperm function, which can be transmitted to their offspring. In humans, paternal obesity results in insulin resistance/type 2 diabetes and increased levels of cortisol in umbilical cord blood, which increases the risk factors for cardiovascular disease. Notably, there is an association between body fat in parents and the prevalence of obesity in their daughters. In animals, paternal obesity led to offspring alterations on glucose-insulin homeostasis, hepatic lipogenesis, hypothalamus/feeding behavior, kidney of the offspring; it also impairs the reproductive potential of male offspring with sperm oxidative stress and mitochondrial dysfunction. An explanation for these observations (human and animal) is epigenetics, considered the primary tool for the transmission of phenotypes from the father to offspring, such as DNA methylation, histone modifications, and non-coding RNA. Paternal obesity can induce programmed phenotypes in offspring through epigenetics. Therefore, it can be considered a public health problem, affecting the children's future life. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  5. Exposing native cyprinid (Barbus plebejus) juveniles to river sediments leads to gonadal alterations, genotoxic effects and thyroid disruption.

    Science.gov (United States)

    Viganò, Luigi; De Flora, Silvio; Gobbi, Marco; Guiso, Giovanna; Izzotti, Alberto; Mandich, Alberta; Mascolo, Giuseppe; Roscioli, Claudio

    2015-12-01

    Juveniles (50 days post hatch) of a native cyprinid fish (Barbus plebejus) were exposed for 7 months to sediments from the River Lambro, a polluted tributary impairing the quality of the River Po for tens of kilometers from their confluence. Sediments were collected upstream of the city of Milan and downstream at the closure of the drainage basin of the River Lambro. Chemical analyses revealed the presence of a complex mixture of bioavailable endocrine-active chemicals, with higher exposure levels in the downstream section of the tributary. Mainly characterized by brominated flame retardants, alkylphenols, polychlorinated biphenyls, and minor co-occurring personal care products and natural hormones, the sediment contamination induced reproductive disorders, as well as other forms of endocrine disruption and toxicity. In particular, exposed male barbel exhibited higher biliary PAH-like metabolites, overexpression of the cyp1a gene, vitellogenin production in all specimens, the presence of oocytes (up to 22% intersex), degenerative alterations in their testis, liver fat vacuolization, a marked depression of total thyroxine (T4) and triiodothyronine (T3) plasma levels, and genotoxic damages determined as hepatic DNA adducts. These results clearly demonstrate that Lambro sediments alone are responsible for recognizable changes in the structure and function of the reproductive and, in general, the endocrine system of a native fish species. In the real environment, exposure to waterborne and food-web sources of chemicals are responsible for additional toxic loads, and the present findings thus provide evidence for a causal role of this tributary in the severe decline observed in barbel in recent decades and raise concern that the fish community of the River Po is exposed to endocrine-mediated health effects along tens of kilometres of its course. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Expression of a dominant negative CELF protein in vivo leads to altered muscle organization, fiber size, and subtype.

    Directory of Open Access Journals (Sweden)

    Dara S Berger

    2011-04-01

    Full Text Available CUG-BP and ETR-3-like factor (CELF proteins regulate tissue- and developmental stage-specific alternative splicing in striated muscle. We previously demonstrated that heart muscle-specific expression of a nuclear dominant negative CELF protein in transgenic mice (MHC-CELFΔ effectively disrupts endogenous CELF activity in the heart in vivo, resulting in impaired cardiac function. In this study, transgenic mice that express the dominant negative protein under a skeletal muscle-specific promoter (Myo-CELFΔ were generated to investigate the role of CELF-mediated alternative splicing programs in normal skeletal muscle.Myo-CELFΔ mice exhibit modest changes in CELF-mediated alternative splicing in skeletal muscle, accompanied by a reduction of endomysial and perimysial spaces, an increase in fiber size variability, and an increase in slow twitch muscle fibers. Weight gain and mean body weight, total number of muscle fibers, and overall muscle strength were not affected.Although these findings demonstrate that CELF activity contributes to the normal alternative splicing of a subset of muscle transcripts in vivo, the mildness of the effects in Myo-CELFΔ muscles compared to those in MHC-CELFΔ hearts suggests CELF activity may be less determinative for alternative splicing in skeletal muscle than in heart muscle. Nonetheless, even these small changes in CELF-mediated splicing regulation were sufficient to alter muscle organization and muscle fiber properties affected in myotonic dystrophy. This lends further evidence to the hypothesis that dysregulation of CELF-mediated alternative splicing programs may be responsible for the disruption of these properties during muscle pathogenesis.

  7. Exposure to monomethylarsonous acid (MMA(III)) leads to altered selenoprotein synthesis in a primary human lung cell model.

    Science.gov (United States)

    Meno, Sarah R; Nelson, Rebecca; Hintze, Korry J; Self, William T

    2009-09-01

    Monomethylarsonous acid (MMA(III)), a trivalent metabolite of arsenic, is highly cytotoxic and recent cell culture studies suggest that it might act as a carcinogen. The general consensus of studies indicates that the cytotoxicity of MMA(III) is a result of increased levels of reactive oxygen species (ROS). A longstanding relationship between arsenic and selenium metabolism has led to the use of selenium as a supplement in arsenic exposed populations, however the impact of organic arsenicals (methylated metabolites) on selenium metabolism is still poorly understood. In this study we determined the impact of exposure to MMA(III) on the regulation of expression of TrxR1 and its activity using a primary lung fibroblast line, WI-38. The promoter region of the gene encoding the selenoprotein thioredoxin reductase 1 (TrxR1) contains an antioxidant responsive element (ARE) that has been shown to be activated in the presence of electrophilic compounds. Results from radiolabeled selenoproteins indicate that exposure to low concentrations of MMA(III) resulted in increased synthesis of TrxR1 in WI-38 cells, and lower incorporation of selenium into other selenoproteins. MMA(III) treatment led to increased mRNA encoding TrxR1 in WI-38 cells, while lower levels of mRNA coding for cellular glutathione peroxidase (cGpx) were detected in exposed cells. Luciferase activity of TrxR1 promoter fusions increased with addition of MMA(III), as did expression of a rat quinone reductase (QR) promoter fusion construct. However, MMA(III) induction of the TRX1 promoter fusion was abrogated when the ARE was mutated, suggesting that this regulation is mediated via the ARE. These results indicate that MMA(III) alters the expression of selenoproteins based on a selective induction of TrxR1, and this response to exposure to organic arsenicals that requires the ARE element.

  8. Loss of malic enzymes leads to metabolic imbalance and altered levels of trehalose and putrescine in the bacterium Sinorhizobium meliloti.

    Science.gov (United States)

    Zhang, Ye; Smallbone, Laura Anne; diCenzo, George C; Morton, Richard; Finan, Turlough M

    2016-07-26

    Malic enzymes decarboxylate the tricarboxylic acid (TCA) cycle intermediate malate to the glycolytic end-product pyruvate and are well positioned to regulate metabolic flux in central carbon metabolism. Despite the wide distribution of these enzymes, their biological roles are unclear in part because the reaction catalyzed by these enzymes can be by-passed by other pathways. The N2-fixing alfalfa symbiont Sinorhizobium meliloti contains both a NAD(P)-malic enzyme (DME) and a separate NADP-malic enzyme (TME) and to help understand the role of these enzymes, we investigated growth, metabolomic, and transcriptional consequences resulting from loss of these enzymes in free-living cells. Loss of DME, TME, or both enzymes had no effect on growth with the glycolytic substrate, glucose. In contrast, the dme mutants, but not tme, grew slowly on the gluconeogenic substrate succinate and this slow growth was further reduced upon the addition of glucose. The dme mutant strains incubated with succinate accumulated trehalose and hexose sugar phosphates, secreted malate, and relative to wild-type, these cells had moderately increased transcription of genes involved in gluconeogenesis and pathways that divert metabolites away from the TCA cycle. While tme mutant cells grew at the same rate as wild-type on succinate, they accumulated the compatible solute putrescine. NAD(P)-malic enzyme (DME) of S. meliloti is required for efficient metabolism of succinate via the TCA cycle. In dme mutants utilizing succinate, malate accumulates and is excreted and these cells appear to increase metabolite flow via gluconeogenesis with a resulting increase in the levels of hexose-6-phosphates and trehalose. For cells utilizing succinate, TME activity alone appeared to be insufficient to produce the levels of pyruvate required for efficient TCA cycle metabolism. Putrescine was found to accumulate in tme cells growing with succinate, and whether this is related to altered levels of NADPH requires

  9. Glycogen metabolism in brain and neurons - astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure.

    Science.gov (United States)

    Baranowska-Bosiacka, Irena; Falkowska, Anna; Gutowska, Izabela; Gąssowska, Magdalena; Kolasa-Wołosiuk, Agnieszka; Tarnowski, Maciej; Chibowska, Karina; Goschorska, Marta; Lubkowska, Anna; Chlubek, Dariusz

    2017-09-01

    Lead (Pb) is an environmental neurotoxin which particularly affects the developing brain but the molecular mechanism of its neurotoxicity still needs clarification. The aim of this paper was to examine whether pre- and neonatal exposure to Pb (concentration of Pb in rat offspring blood below the "threshold level") may affect the brain's energy metabolism in neurons and astrocytes via the amount of available glycogen. We investigated the glycogen concentration in the brain, as well as the expression of the key enzymes involved in glycogen metabolism in brain: glycogen synthase 1 (Gys1), glycogen phosphorylase (PYGM, an isoform active in astrocytes; and PYGB, an isoform active in neurons) and phosphorylase kinase β (PHKB). Moreover, the expression of connexin 43 (Cx43) was evaluated to analyze whether Pb poisoning during the early phase of life may affect the neuron-astrocytes' metabolic cooperation. This work shows for the first time that exposure to Pb in early life can impair brain energy metabolism by reducing the amount of glycogen and decreasing the rate of its metabolism. This reduction in brain glycogen level was accompanied by a decrease in Gys1 expression. We noted a reduction in the immunoreactivity and the gene expression of both PYGB and PYGM isoform, as well as an increase in the expression of PHKB in Pb-treated rats. Moreover, exposure to Pb induced decrease in connexin 43 immunoexpression in all the brain structures analyzed, both in astrocytes as well as in neurons. Our data suggests that exposure to Pb in the pre- and neonatal periods results in a decrease in the level of brain glycogen and a reduction in the rate of its metabolism, thereby reducing glucose availability, which as a further consequence may lead to the impairment of brain energy metabolism and the metabolic cooperation between neurons and astrocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Altered functional connectivity links in neuroleptic-naïve and neuroleptic-treated patients with schizophrenia, and their relation to symptoms including volition

    Directory of Open Access Journals (Sweden)

    Weidan Pu

    2014-01-01

    Full Text Available In order to analyze functional connectivity in untreated and treated patients with schizophrenia, resting-state fMRI data were obtained for whole-brain functional connectivity analysis from 22 first-episode neuroleptic-naïve schizophrenia (NNS, 61 first-episode neuroleptic-treated schizophrenia (NTS patients, and 60 healthy controls (HC. Reductions were found in untreated and treated patients in the functional connectivity between the posterior cingulate gyrus and precuneus, and this was correlated with the reduction in volition from the Positive and Negative Symptoms Scale (PANSS, that is in the willful initiation, sustenance, and control of thoughts, behavior, movements, and speech, and with the general and negative symptoms. In addition in both patient groups interhemispheric functional connectivity was weaker between the orbitofrontal cortex, amygdala and temporal pole. These functional connectivity changes and the related symptoms were not treated by the neuroleptics. Differences between the patient groups were that there were more strong functional connectivity links in the NNS patients (including in hippocampal, frontal, and striatal circuits than in the NTS patients. These findings with a whole brain analysis in untreated and treated patients with schizophrenia provide evidence on some of the brain regions implicated in the volitional, other general, and negative symptoms, of schizophrenia that are not treated by neuroleptics so have implications for the development of other treatments; and provide evidence on some brain systems in which neuroleptics do alter the functional connectivity.

  11. Environmental Toxin Acrolein Alters Levels of Endogenous Lipids, Including TRP Agonists: A Potential Mechanism for Headache Driven by TRPA1 Activation.

    Science.gov (United States)

    Leishman, Emma; Kunkler, Phillip E; Manchanda, Meera; Sangani, Kishan; Stuart, Jordyn M; Oxford, Gerry S; Hurley, Joyce H; Bradshaw, Heather B

    2017-01-01

    Exposure to airborne toxins can trigger headaches, but the mechanisms are not well understood. Some environmental toxins, such as acrolein, activate transient receptor potential ankyrin 1 (TRPA1), a receptor involved in pain sensation that is highly expressed in the trigeminovascular system. It has been shown in rat models that repeated exposure to acrolein induces trigeminovascular sensitization to both TRPA1 and TRP vanilloid 1 (TRPV1) agonists, a phenomenon linked to headache. In this study, we test the hypothesis that the sensitization of trigeminovascular responses in rats after acrolein exposure via inhalation is associated with changes in levels of endogenous lipids, including TRPV1 agonists, in the trigeminal ganglia, trigeminal nucleus, and cerebellum. Lipidomics analysis of 80 lipids was performed on each tissue after acute acrolein, chronic acrolein, or room air control. Both acute and chronic acrolein exposure drove widespread alterations in lipid levels. After chronic acrolein exposure, levels of all 6 N -acyl ethanolamines in the screening library, including the endogenous cannabinoid and TRPV1 agonist, N -arachidonoyl ethanolamine, were elevated in trigeminal tissue and in the cerebellum. This increase in TRPV1 ligands by acrolein exposure may indicate further downstream signaling, in that we also show here that a combination of these TRPV1 endogenous agonists increases the potency of the individual ligands in TRPV1-HEK cells. In addition to these TRPV1 agonists, 3 TRPV3 antagonists, 4 TRPV4 agonists, and 25 orphan lipids were up and down regulated after acrolein exposure. These data support the hypothesis that lipid signaling may represent a mechanism by which repeated exposure to the TRPA1 agonist and environmental toxin, acrolein, drives trigeminovascular sensitization.

  12. Environmental toxin acrolein alters levels of endogenous lipids, including TRP agonists: A potential mechanism for headache driven by TRPA1 activation

    Directory of Open Access Journals (Sweden)

    Emma Leishman

    2017-01-01

    Full Text Available Exposure to airborne toxins can trigger headaches, but the mechanisms are not well understood. Some environmental toxins, such as acrolein, activate transient receptor potential ankyrin 1 (TRPA1, a receptor involved in pain sensation that is highly expressed in the trigeminovascular system. It has been shown in rat models that repeated exposure to acrolein induces trigeminovascular sensitization to both TRPA1 and TRP vanilloid 1 (TRPV1 agonists, a phenomenon linked to headache. In this study, we test the hypothesis that the sensitization of trigeminovascular responses in rats after acrolein exposure via inhalation is associated with changes in levels of endogenous lipids, including TRPV1 agonists, in the trigeminal ganglia, trigeminal nucleus, and cerebellum. Lipidomics analysis of 80 lipids was performed on each tissue after acute acrolein, chronic acrolein, or room air control. Both acute and chronic acrolein exposure drove widespread alterations in lipid levels. After chronic acrolein exposure, levels of all 6 N-acyl ethanolamines in the screening library, including the endogenous cannabinoid and TRPV1 agonist, N-arachidonoyl ethanolamine, were elevated in trigeminal tissue and in the cerebellum. This increase in TRPV1 ligands by acrolein exposure may indicate further downstream signaling, in that we also show here that a combination of these TRPV1 endogenous agonists increases the potency of the individual ligands in TRPV1-HEK cells. In addition to these TRPV1 agonists, 3 TRPV3 antagonists, 4 TRPV4 agonists, and 25 orphan lipids were up and down regulated after acrolein exposure. These data support the hypothesis that lipid signaling may represent a mechanism by which repeated exposure to the TRPA1 agonist and environmental toxin, acrolein, drives trigeminovascular sensitization. Keywords: Lipidomics, Endogenous cannabinoid, TRPA1, TRPV1, Lipoamine, Acrolein, Migraine

  13. Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition.

    Science.gov (United States)

    Pop, Mihai; Walker, Alan W; Paulson, Joseph; Lindsay, Brianna; Antonio, Martin; Hossain, M Anowar; Oundo, Joseph; Tamboura, Boubou; Mai, Volker; Astrovskaya, Irina; Corrada Bravo, Hector; Rance, Richard; Stares, Mark; Levine, Myron M; Panchalingam, Sandra; Kotloff, Karen; Ikumapayi, Usman N; Ebruke, Chinelo; Adeyemi, Mitchell; Ahmed, Dilruba; Ahmed, Firoz; Alam, Meer Taifur; Amin, Ruhul; Siddiqui, Sabbir; Ochieng, John B; Ouma, Emmanuel; Juma, Jane; Mailu, Euince; Omore, Richard; Morris, J Glenn; Breiman, Robert F; Saha, Debasish; Parkhill, Julian; Nataro, James P; Stine, O Colin

    2014-06-27

    Diarrheal diseases continue to contribute significantly to morbidity and mortality in infants and young children in developing countries. There is an urgent need to better understand the contributions of novel, potentially uncultured, diarrheal pathogens to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease. We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composition in children under five years of age who have been diagnosed with moderate to severe diarrhea (MSD) with the microbiota from diarrhea-free controls. Our study includes 992 children from four low-income countries in West and East Africa, and Southeast Asia. Known pathogens, as well as bacteria currently not considered as important diarrhea-causing pathogens, are positively associated with MSD, and these include Escherichia/Shigella, and Granulicatella species, and Streptococcus mitis/pneumoniae groups. In both cases and controls, there tend to be distinct negative correlations between facultative anaerobic lineages and obligate anaerobic lineages. Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of Prevotella and in MSD cases from high to low levels of Escherichia/Shigella in younger versus older children; however, there was significant variation among many genera by both site and age. Our findings expand the current understanding of microbiota-associated diarrhea pathogenicity in young children from developing countries. Our findings are necessarily based on correlative analyses and must be further validated through epidemiological and molecular techniques.

  14. Disturbed Placental Imprinting in Preeclampsia Leads to Altered Expression of DLX5, a Human-Specific Early Trophoblast Marker.

    Science.gov (United States)

    Zadora, Julianna; Singh, Manvendra; Herse, Florian; Przybyl, Lukasz; Haase, Nadine; Golic, Michaela; Yung, Hong Wa; Huppertz, Berthold; Cartwright, Judith E; Whitley, Guy; Johnsen, Guro M; Levi, Giovanni; Isbruch, Annette; Schulz, Herbert; Luft, Friedrich C; Müller, Dominik N; Staff, Anne Cathrine; Hurst, Laurence D; Dechend, Ralf; Izsvák, Zsuzsanna

    2017-11-07

    Preeclampsia is a complex and common human-specific pregnancy syndrome associated with placental pathology. The human specificity provides both intellectual and methodological challenges, lacking a robust model system. Given the role of imprinted genes in human placentation and the vulnerability of imprinted genes to loss of imprinting changes, there has been extensive speculation, but no robust evidence, that imprinted genes are involved in preeclampsia. Our study aims to investigate whether disturbed imprinting contributes to preeclampsia. We first aimed to confirm that preeclampsia is a disease of the placenta by generating and analyzing genome-wide molecular data on well-characterized patient material. We performed high-throughput transcriptome analyses of multiple placenta samples from healthy controls and patients with preeclampsia. Next, we identified differentially expressed genes in preeclamptic placentas and intersected them with the list of human imprinted genes. We used bioinformatics/statistical analyses to confirm association between imprinting and preeclampsia and to predict biological processes affected in preeclampsia. Validation included epigenetic and cellular assays. In terms of human specificity, we established an in vitro invasion-differentiation trophoblast model. Our comparative phylogenetic analysis involved single-cell transcriptome data of human, macaque, and mouse preimplantation embryogenesis. We found disturbed placental imprinting in preeclampsia and revealed potential candidates, including GATA3 and DLX5 , with poorly explored imprinted status and no prior association with preeclampsia. As a result of loss of imprinting, DLX5 was upregulated in 69% of preeclamptic placentas. Levels of DLX5 correlated with classic preeclampsia markers. DLX5 is expressed in human but not in murine trophoblast. The DLX5 high phenotype resulted in reduced proliferation, increased metabolism, and endoplasmic reticulum stress-response activation in

  15. Bisphenol-A exposure during adolescence leads to enduring alterations in cognition and dendritic spine density in adult male and female rats.

    Science.gov (United States)

    Bowman, Rachel E; Luine, Victoria; Diaz Weinstein, Samantha; Khandaker, Hameda; DeWolf, Sarah; Frankfurt, Maya

    2015-03-01

    We have previously demonstrated that adolescent exposure of rats to bisphenol-A (BPA), an environmental endocrine disrupter, increases anxiety, impairs spatial memory, and decreases dendritic spine density in the CA1 region of the hippocampus (CA1) and medial prefrontal cortex (mPFC) when measured in adolescents in both sexes. The present study examined whether the behavioral and morphological alterations following BPA exposure during adolescent development are maintained into adulthood. Male and female, adolescent rats received BPA, 40μg/kg/bodyweight, or control treatments for one week. In adulthood, subjects were tested for anxiety and locomotor activity, spatial memory, non-spatial visual memory, and sucrose preference. Additionally, stress-induced serum corticosterone levels and dendritic spine density in the mPFC and CA1 were measured. BPA-treated males, but not females, had decreased arm visits on the elevated plus maze, but there was no effect on anxiety. Non-spatial memory, object recognition, was also decreased in BPA treated males, but not in females. BPA exposure did not alter spatial memory, object placement, but decreased exploration during the tasks in both sexes. No significant group differences in sucrose preference or serum corticosterone levels in response to a stress challenge were found. However, BPA exposure, regardless of sex, significantly decreased spine density of both apical and basal dendrites on pyramidal cells in CA1 but had no effect in the mPFC. Current data are discussed in relation to BPA dependent changes, which were present during adolescence and did, or did not, endure into adulthood. Overall, adolescent BPA exposure, below the current reference safe daily limit set by the U.S.E.P.A., leads to alterations in some behaviors and neuronal morphology that endure into adulthood. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Occurrence of cleft-palate and alteration of Tgf-β(3) expression and the mechanisms leading to palatal fusion in mice following dietary folic-acid deficiency.

    Science.gov (United States)

    Maldonado, Estela; Murillo, Jorge; Barrio, Carmen; del Río, Aurora; Pérez-Miguelsanz, Juliana; López-Gordillo, Yamila; Partearroyo, Teresa; Paradas, Irene; Maestro, Carmen; Martínez-Sanz, Elena; Varela-Moreiras, Gregorio; Martínez-Álvarez, Concepción

    2011-01-01

    Folic acid (FA) is essential for numerous bodily functions. Its decrease during pregnancy has been associated with an increased risk of congenital malformations in the progeny. The relationship between FA deficiency and the appearance of cleft palate (CP) is controversial, and little information exists on a possible effect of FA on palate development. We investigated the effect of a 2-8 weeks' induced FA deficiency in female mice on the development of CP in their progeny as well as the mechanisms leading to palatal fusion, i.e. cell proliferation, cell death, and palatal-shelf adhesion and fusion. We showed that an 8 weeks' maternal FA deficiency caused complete CP in the fetuses although a 2 weeks' maternal FA deficiency was enough to alter all the mechanisms analyzed. Since transforming growth factor-β(3) (TGF-β(3)) is crucial for palatal fusion and since most of the mechanisms impaired by FA deficiency were also observed in the palates of Tgf-β(3)null mutant mice, we investigated the presence of TGF-β(3) mRNA, its protein and phospho-SMAD2 in FA-deficient (FAD) mouse palates. Our results evidenced a large reduction in Tgf-β(3) expression in palates of embryos of dams fed an FAD diet for 8 weeks; Tgf-β(3) expression was less reduced in palates of embryos of dams fed an FAD diet for 2 weeks. Addition of TGF-β(3) to palatal-shelf cultures of embryos of dams fed an FAD diet for 2 weeks normalized all the altered mechanisms. Thus, an insufficient folate status may be a risk factor for the development of CP in mice, and exogenous TGF-β(3) compensates this deficit in vitro. Copyright © 2011 S. Karger AG, Basel.

  17. Genetic alteration of UDP-rhamnose metabolism in Botrytis cinerea leads to the accumulation of UDP-KDG that adversely affects development and pathogenicity.

    Science.gov (United States)

    Ma, Liang; Salas, Omar; Bowler, Kyle; Oren-Young, Liat; Bar-Peled, Maor; Sharon, Amir

    2017-02-01

    Botrytis cinerea is a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops. A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose-containing glycans in these mutant strains. Deletion of bcdh or double deletion of both bcdh and bcer has no apparent effect on fungal development or pathogenicity. Interestingly, deletion of the bcer gene alone adversely affects fungal development, giving rise to altered hyphal growth and morphology, as well as reduced sporulation, sclerotia production and virulence. Treatments with wall stressors suggest the alteration of cell wall integrity. Analysis of nucleotide sugars reveals the accumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain. UDP-KDG could not be detected in hyphae of the wild-type strain, indicating fast conversion to UDP-rhamnose by the BcEr enzyme. The correlation between high UDP-KDG and modified cell wall and developmental defects raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition, and hence on virulence. This is the first report demonstrating that the accumulation of a minor nucleotide sugar intermediate has such a profound and adverse effect on a fungus. The ability to identify molecules that inhibit Er (also known as NRS/ER) enzymes or mimic UDP-KDG may lead to the development of new antifungal drugs. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  18. Determining a threshold sub-acute dose leading to minimal physiological alterations following prolonged exposure to the nerve agent VX in rats.

    Science.gov (United States)

    Bloch-Shilderman, E; Rabinovitz, I; Egoz, I; Yacov, G; Allon, N; Nili, U

    2018-02-01

    VX, a potent inhibitor of cholinesterase (ChE), is considered as one of the most toxic, persistent and least volatile nerve agents. VX is absorbed in various environmental surfaces and is gradually released long after its initial dispersal. Its toxicity is mainly caused by disrupting central and peripheral cholinergic nervous system activity, leading to potential long-term detrimental effects on health. The primary objective of the present study was to assess the threshold VX dose leading to minimal physiological alterations following prolonged VX exposure. Characterization of such a threshold is crucial for dealing with unresolved operative dilemmas such as when it is safe enough to resettle a population that has been evacuated from a VX-contaminated area. Rats, continuously exposed to various doses of VX (0.225-45 µg/kg/day) for 4 weeks via implanted mini-osmotic pumps, showed a dose-dependent and continuous decrease in ChE activity in whole blood, brain and muscles, ranging between 20 and 100%. Exposure to 13.5 µg/kg/day led to a stable low ChE activity level (~ 20%), accompanied by transient and negligible electrocorticogram spectral power transformations, especially in the theta and alpha brain wave frequencies, and a significant decrease in total brain M2 receptor density. These changes were neither accompanied by observable signs of intoxication nor by changes in motor function, circadian rhythm or TSPO level (a reliable marker of brain damage). Following exposure to lower doses of 2.25 and 0.225 µg/kg/day, the only change measured was a reduction in ChE activity of 60 and 20%, respectively. Based on these results, we delineate ChE inhibition as the physiological measure most susceptible to alterations following prolonged VX exposure, and determine for the first time the threshold sub-acute VX dose for minimal physiological effects (up to 20% reduction in ChE activity) in the rat as 0.225 µg/kg/day.

  19. Orbital fracture leading to severe multifascial space infection including the parapharyngeal space: a report of a case and review of the literature.

    Science.gov (United States)

    Park, Chan; Marchiori, Erica; Barber, Jacob; Cardon, Curtis

    2014-09-01

    Orbital trauma can result in periorbital and orbital infections. Orbital infections have been classified by Chandler et al in 1970 to their anatomic location and boundaries. This case report describes a patient who developed a severe orbital infection following orbital fractures. The infection progressed to the parapharyngeal space. The patient required multiple incision and drainage surgeries and tissue debridements to have clinical resolution. To our knowledge, there has not been a case described in the literature of an orbital infection progressing to the parapharyngeal space. A literature review of orbital trauma leading to infection discusses the pathogenesis of the infections. This case demonstrates that close clinical follow-up and appropriate medical management of comorbidities that put a patient at higher risk of developing an infection is of the utmost importance in the treatment of maxillofacial trauma patients.

  20. The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen–encoding var genes

    Science.gov (United States)

    Tonkin-Hill, Gerry Q.; Trianty, Leily; Noviyanti, Rintis; Nguyen, Hanh H. T.; Sebayang, Boni F.; Lampah, Daniel A.; Marfurt, Jutta; Cobbold, Simon A.; Rambhatla, Janavi S.; McConville, Malcolm J.; Rogerson, Stephen J.; Brown, Graham V.; Day, Karen P.; Price, Ric N.; Anstey, Nicholas M.

    2018-01-01

    Within the human host, the malaria parasite Plasmodium falciparum is exposed to multiple selection pressures. The host environment changes dramatically in severe malaria, but the extent to which the parasite responds to—or is selected by—this environment remains unclear. From previous studies, the parasites that cause severe malaria appear to increase expression of a restricted but poorly defined subset of the PfEMP1 variant, surface antigens. PfEMP1s are major targets of protective immunity. Here, we used RNA sequencing (RNAseq) to analyse gene expression in 44 parasite isolates that caused severe and uncomplicated malaria in Papuan patients. The transcriptomes of 19 parasite isolates associated with severe malaria indicated that these parasites had decreased glycolysis without activation of compensatory pathways; altered chromatin structure and probably transcriptional regulation through decreased histone methylation; reduced surface expression of PfEMP1; and down-regulated expression of multiple chaperone proteins. Our RNAseq also identified novel associations between disease severity and PfEMP1 transcripts, domains, and smaller sequence segments and also confirmed all previously reported associations between expressed PfEMP1 sequences and severe disease. These findings will inform efforts to identify vaccine targets for severe malaria and also indicate how parasites adapt to—or are selected by—the host environment in severe malaria. PMID:29529020

  1. Novel mutations causing biotinidase deficiency in individuals identified by newborn screening in Michigan including an unique intronic mutation that alters mRNA expression of the biotinidase gene.

    Science.gov (United States)

    Li, H; Spencer, L; Nahhas, F; Miller, J; Fribley, A; Feldman, G; Conway, R; Wolf, B

    2014-07-01

    Biotinidase deficiency (BD) is an autosomal recessive disorder resulting in the inability to recycle the vitamin biotin. Individuals with biotinidase deficiency can develop neurological and cutaneous symptoms if they are not treated with biotin. To date, more than 165 mutations in the biotinidase gene (BTD) have been reported. Essentially all the mutations result in enzymatic activities with less than 10% of mean normal serum enzyme activity (profound biotinidase deficiency) with the exception of the c.1330G>C (p.D444H) mutation, which results in an enzyme having 50% of mean normal serum activity and causes partial biotinidase deficiency (10-30% of mean normal serum biotinidase activity) if there is a mutation for profound biotinidase deficiency on the second allele. We now reported eight novel mutations in ten children identified by newborn screening in Michigan from 1988 to the end of 2012. Interestingly, one intronic mutation, c.310-15delT, results in an approximately two-fold down-regulation of BTD mRNA expression by Quantitative real-time reverse-transcription PCR (qRT-PCR). This is the first report of an intronic mutation in the BTD gene with demonstration of its effect on enzymatic activity by altering mRNA expression. This study identified three other mutations likely to cause partial biotinidase deficiency. These results emphasize the importance of full gene sequencing of BTD on patients with biotinidase deficiency to better understand the genotype and phenotype correlation in the future. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Small changes in environmental parameters lead to alterations in antibiotic resistance, cell morphology and membrane fatty acid composition in Staphylococcus lugdunensis.

    Directory of Open Access Journals (Sweden)

    Marcus J Crompton

    Full Text Available Staphylococcus lugdunensis has emerged as a major cause of community-acquired and nosocomial infections. This bacterium can rapidly adapt to changing environmental conditions to survive and capitalize on opportunities to colonize and infect through wound surfaces. It was proposed that S. lugdunensis would have underlying alterations in metabolic homeostasis to provide the necessary levels of adaptive protection. The aims of this project were to examine the impacts of subtle variations in environmental conditions on growth characteristics, cell size and membrane fatty acid composition in S. lugdunensis. Liquid broth cultures of S. lugdunensis were grown under varying combinations of pH (6-8, temperature (35-39°C and osmotic pressure (0-5% sodium chloride w/w to reflect potential ranges of conditions encountered during transition from skin surfaces to invasion of wound sites. The cells were harvested at the mid-exponential phase of growth and assessed for antibiotic minimal inhibitory concentration (MIC, generation time, formation of small colony variants, cell size (by scanning electron microscopy and membrane fatty acid composition. Stress regimes with elevated NaCl concentrations resulted in significantly higher antibiotic resistance (MIC and three of the combinations with 5% NaCl had increased generation times (P<0.05. It was found that all ten experimental growth regimes, including the control and centroid cultures, yielded significantly different profiles of plasma membrane fatty acid composition (P<0.0001. Alterations in cell size (P<0.01 were also observed under the range of conditions with the most substantial reduction occurring when cells were grown at 39°C, pH 8 (514±52 nm, mean ± Standard Deviation compared with cells grown under control conditions at 37°C with pH 7 (702±76 nm, P<0.01. It was concluded that S. lugdunensis responded to slight changes in environmental conditions by altering plasma membrane fatty acid composition

  3. Protective roles of selenium and zinc against postnatal protein-undernutrition-induced alterations in Ca(2+)-homeostasis leading to cognitive deficits in Wistar rats.

    Science.gov (United States)

    Adebayo, Olusegun L; Sandhir, Rajat; Adenuga, Gbenga A

    2015-06-01

    Postnatal protein-undernutrition impacts on mental development and cognition in children and can lead to problem with attention and unresponsiveness which compromise children's ability to learn. These behavioral disorders might be due to alteration in calcium homeostasis as calcium plays critical roles in fundamental functions of neuron. The role of low protein diet as well as Se and Zn supplementation on intracellular calcium concentration ([Ca(2+)]i), Ca(2+)-ATPase, Na(+)-K(+)-ATPase, calpain and caspase-3 activities from rat cortex and cerebellum were investigated. Well-fed (WF) and low protein diet-fed (LPDF) rats were given diets containing 16% and 5% casein, respectively, for a period of 10 weeks. Then, the rats were supplemented with Se and Zn at a concentration of 0.15 mgL(-1) and 227 mgL(-1), respectively, in drinking water for 3 weeks. The results obtained from the study showed a significant increase in [Ca(2+)]i; calpain and caspase-3 activities as well as increase transfer latency in water maze study and reductions in Ca(2+)-ATPase and Na(+)-K(+)-ATPase activities for LPDF rats compared to WF rats. Se and Zn supplementation to LPDF rats reversed the elevation in [Ca(2+)]i, calpain and caspase-3 activities and restored the cognitive deficits and the activities of Ca(2+)-ATPase and Na(+)-K(+)-ATPase. Conclusively, protein-undernutrition results in the accumulation of synaptosomal calcium and inhibition of calcium transporters presumably via free radical generations and results in cognitive impairment which also probably results from neuronal death in rats through calpain activation and the caspase cascade mechanisms. However, Se and Zn supplementations ameliorated the anomalies observed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Molecular alterations in lesions of anogenital mammary-like glands and their mammary counterparts including hidradenoma papilliferum, intraductal papilloma, fibroadenoma and phyllodes tumor.

    Science.gov (United States)

    Konstantinova, Anastasia M; Vanecek, Tomas; Martinek, Petr; Kyrpychova, Liubov; Spagnolo, Dominic V; Stewart, Colin J R; Portelli, Francesca; Michal, Michal; Kazakov, Dmitry V

    2017-06-01

    Lesions affecting anogenital mammary-like glands (AGMLG) are histopathologically very similar to those seen in the breast but whether this morphological similarity is also reflected at the genetic level is unknown. To compare the underlying molecular mechanisms in lesions of AGMLG and their mammary counterparts, we analyzed the mutational profile of 16 anogenital neoplasms including 5 hidradenomas papilliferum (HP), 1 lesion with features of HP and fibroadenoma (FA), 7 FA, 3 phyllodes tumors (PhT)) and 18 analogous breast lesions (6 intraductal papillomas (IDP), 9 FA, and 3 PhT) by high-coverage next generation sequencing (NGS) using a panel comprising 50 cancer-related genes. Additionally, all cases were analyzed for the presence of a mutation in the MED12 gene. All detected mutations with allele frequencies over 20% were independently validated by Sanger sequencing (concordance: 100%). Mutations in PIK3CA, AKT1, MET, ABL1 and TP53 genes were found in lesions of AGMLG and also their mammary counterparts. The PI3K-AKT cascade plays a role in tumors arising at both sites. It appears that some histopathologically similar anogenital and breast lesions develop along similar molecular pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Targeted mutation of Δ12 and Δ15 desaturase genes in hemp produce major alterations in seed fatty acid composition including a high oleic hemp oil.

    Science.gov (United States)

    Bielecka, Monika; Kaminski, Filip; Adams, Ian; Poulson, Helen; Sloan, Raymond; Li, Yi; Larson, Tony R; Winzer, Thilo; Graham, Ian A

    2014-06-01

    We used expressed sequence tag library and whole genome sequence mining to identify a suite of putative desaturase genes representing the four main activities required for production of polyunsaturated fatty acids in hemp seed oil. Phylogenetic-based classification and developing seed transcriptome analysis informed selection for further analysis of one of seven Δ12 desaturases and one of three Δ15 desaturases that we designate CSFAD2A and CSFAD3A, respectively. Heterologous expression of corresponding cDNAs in Saccharomyces cerevisiae showed CSFAD2A to have Δx+3 activity, while CSFAD3A activity was exclusively at the Δ15 position. TILLING of an ethyl methane sulphonate mutagenized population identified multiple alleles including non-sense mutations in both genes and fatty acid composition of seed oil confirmed these to be the major Δ12 and Δ15 desaturases in developing hemp seed. Following four backcrosses and sibling crosses to achieve homozygosity, csfad2a-1 was grown in the field and found to produce a 70 molar per cent high oleic acid (18:1(Δ9) ) oil at yields similar to wild type. Cold-pressed high oleic oil produced fewer volatiles and had a sevenfold increase in shelf life compared to wild type. Two low abundance octadecadienoic acids, 18:2(Δ6,9) and 18:2(Δ9,15), were identified in the high oleic oil, and their presence suggests remaining endogenous desaturase activities utilize the increased levels of oleic acid as substrate. Consistent with this, CSFAD3A produces 18:2(Δ9,15) from endogenous 18:1(Δ9) when expressed in S. cerevisiae. This work lays the foundation for the development of additional novel oil varieties in this multipurpose low input crop. © 2014 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  6. Increased leaf mesophyll porosity following transient retinoblastoma-related protein silencing is revealed by microcomputed tomography imaging and leads to a system-level physiological response to the altered cell division pattern.

    Science.gov (United States)

    Dorca-Fornell, Carmen; Pajor, Radoslaw; Lehmeier, Christoph; Pérez-Bueno, Marísa; Bauch, Marion; Sloan, Jen; Osborne, Colin; Rolfe, Stephen; Sturrock, Craig; Mooney, Sacha; Fleming, Andrew

    2013-12-01

    The causal relationship between cell division and growth in plants is complex. Although altered expression of cell-cycle genes frequently leads to altered organ growth, there are many examples where manipulation of the division machinery leads to a limited outcome at the level of organ form, despite changes in constituent cell size. One possibility, which has been under-explored, is that altered division patterns resulting from manipulation of cell-cycle gene expression alter the physiology of the organ, and that this has an effect on growth. We performed a series of experiments on retinoblastoma-related protein (RBR), a well characterized regulator of the cell cycle, to investigate the outcome of altered cell division on leaf physiology. Our approach involved combination of high-resolution microCT imaging and physiological analysis with a transient gene induction system, providing a powerful approach for the study of developmental physiology. Our investigation identifies a new role for RBR in mesophyll differentiation that affects tissue porosity and the distribution of air space within the leaf. The data demonstrate the importance of RBR in early leaf development and the extent to which physiology adapts to modified cellular architecture resulting from altered cell-cycle gene expression. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

  7. Deficiency of the miR-29a/b-1 cluster leads to ataxic features and cerebellar alterations in mice

    DEFF Research Database (Denmark)

    Papadopoulou, Aikaterini S; Serneels, Lutgarde; Achsel, Tilmann

    2015-01-01

    miR-29 is expressed strongly in the brain and alterations in expression have been linked to several neurological disorders. To further explore the function of this miRNA in the brain, we generated miR-29a/b-1 knockout animals. Knockout mice develop a progressive disorder characterized by locomoto...

  8. Substitution of aspartic acid-686 by histidine or asparagine in the human androgen receptor leads to a functionally inactive protein with altered hormone-binding characteristics

    NARCIS (Netherlands)

    Ris-Stalpers, C.; Trifiro, M. A.; Kuiper, G. G.; Jenster, G.; Romalo, G.; Sai, T.; van Rooij, H. C.; Kaufman, M.; Rosenfield, R. L.; Liao, S.

    1991-01-01

    We have identified two different single nucleotide alterations in codon 686 (GAC; aspartic acid) in exon 4 of the human androgen receptor gene in three unrelated families with the complete form of androgen insensitivity. One mutation (G----C) results in an aspartic acid----histidine substitution

  9. LEADING WITH LEADING INDICATORS

    International Nuclear Information System (INIS)

    PREVETTE, S.S.

    2005-01-01

    This paper documents Fluor Hanford's use of Leading Indicators, management leadership, and statistical methodology in order to improve safe performance of work. By applying these methods, Fluor Hanford achieved a significant reduction in injury rates in 2003 and 2004, and the improvement continues today. The integration of data, leadership, and teamwork pays off with improved safety performance and credibility with the customer. The use of Statistical Process Control, Pareto Charts, and Systems Thinking and their effect on management decisions and employee involvement are discussed. Included are practical examples of choosing leading indicators. A statistically based color coded dashboard presentation system methodology is provided. These tools, management theories and methods, coupled with involved leadership and employee efforts, directly led to significant improvements in worker safety and health, and environmental protection and restoration at one of the nation's largest nuclear cleanup sites

  10. Mutations in the control of virulence sensor gene from Streptococcus pyogenes after infection in mice lead to clonal bacterial variants with altered gene regulatory activity and virulence.

    Directory of Open Access Journals (Sweden)

    Jeffrey A Mayfield

    Full Text Available The cluster of virulence sensor (CovS/responder (CovR two-component operon (CovRS regulates ∼15% of the genes of the Group A Streptococcal pyogenes (GAS genome. Bacterial clones containing inactivating mutations in the covS gene have been isolated from patients with virulent invasive diseases. We report herein an assessment of the nature and types of covS mutations that can occur in both virulent and nonvirulent GAS strains, and assess whether a nonvirulent GAS can attain enhanced virulence through this mechanism. A group of mice were infected with a globally-disseminated clonal M1T1 GAS (isolate 5448, containing wild-type (WT CovRS (5448/CovR+S+, or less virulent engineered GAS strains, AP53/CovR+S+ and Manfredo M5/CovR+S+. SpeB negative GAS clones from wound sites and/or from bacteria disseminated to the spleen were isolated and the covS gene was subjected to DNA sequence analysis. Numerous examples of inactivating mutations were found in CovS in all regions of the gene. The mutations found included frame-shift insertions and deletions, and in-frame small and large deletions in the gene. Many of the mutations found resulted in early translation termination of CovS. Thus, the covS gene is a genomic mutagenic target that gives GAS enhanced virulence. In cases wherein CovS- was discovered, these clonal variants exhibited high lethality, further suggesting that randomly mutated covS genes occur during the course of infection, and lead to the development of a more invasive infection.

  11. Characterization and Alteration of Wettability States of Alaskan Reserviors to Improve Oil Recovery Efficiency (including the within-scope expansion based on Cyclic Water Injection - a pulsed waterflood for Enhanced Oil Recovery)

    Energy Technology Data Exchange (ETDEWEB)

    Abhijit Dandekar; Shirish Patil; Santanu Khataniar

    2008-12-31

    , cyclic water injection tests using high as well as low salinity were also conducted on several representative ANS core samples. These results indicate that less pore volume of water is required to recover the same amount of oil as compared with continuous water injection. Additionally, in cyclic water injection, oil is produced even during the idle time of water injection. It is understood that the injected brine front spreads/smears through the pores and displaces oil out uniformly rather than viscous fingering. The overall benefits of this project include increased oil production from existing Alaskan reservoirs. This conclusion is based on the performed experiments and results obtained on low-salinity water injection (including ANS lake water), vis-a-vis slightly altering the wetting conditions. Similarly, encouraging cyclic water-injection test results indicate that this method can help achieve residual oil saturation earlier than continuous water injection. If proved in field, this would be of great use, as more oil can be recovered through cyclic water injection for the same amount of water injected.

  12. Intermittent Ethanol during Adolescence Leads to Lasting Behavioral Changes in Adulthood and Alters Gene Expression and Histone Methylation in the PFC

    Directory of Open Access Journals (Sweden)

    Jennifer T. Wolstenholme

    2017-09-01

    Full Text Available Adolescents primarily consume alcohol in binges, which can be particularly harmful to the developing frontal cortex and increase risk for an adult alcohol use disorder. We conducted a study investigating immediate and long lasting changes to the prefrontal cortex (PFC transcriptome to determine the molecular mechanisms underlying adult ethanol behavioral sensitivity following binge ethanol in adolescence. DBA/2J mice were orally dosed with 4 g/kg ethanol intermittently from day 29 to 42. Adolescent mice were tested for anxiety-like behavior and ethanol sensitivity using the loss of righting reflex task. As adults, mice were tested for cognitive changes using the novel object recognition task, ethanol-induced anxiolysis and ethanol sensitivity. Adolescent binge ethanol altered ethanol sensitivity in young mice and led to lasting memory deficits in the object recognition test and greater ethanol sensitivity in adulthood. Using genomic profiling of transcripts in the PFC, we found that binge ethanol reduced myelin-related gene expression and altered chromatin modifying genes involved in histone demethylation at H3K9 and H3K36. We hypothesize that ethanol’s actions on histone methylation may be a switch for future transcriptional changes that underlie the behavioral changes lasting into adulthood.

  13. Red:far-red light conditions affect the emission of volatile organic compounds from barley (Hordeum vulgare), leading to altered biomass allocation in neighbouring plants.

    Science.gov (United States)

    Kegge, Wouter; Ninkovic, Velemir; Glinwood, Robert; Welschen, Rob A M; Voesenek, Laurentius A C J; Pierik, Ronald

    2015-05-01

    Volatile organic compounds (VOCs) play various roles in plant-plant interactions, and constitutively produced VOCs might act as a cue to sense neighbouring plants. Previous studies have shown that VOCs emitted from the barley (Hordeum vulgare) cultivar 'Alva' cause changes in biomass allocation in plants of the cultivar 'Kara'. Other studies have shown that shading and the low red:far-red (R:FR) conditions that prevail at high plant densities can reduce the quantity and alter the composition of the VOCs emitted by Arabidopsis thaliana, but whether this affects plant-plant signalling remains unknown. This study therefore examines the effects of far-red light enrichment on VOC emissions and plant-plant signalling between 'Alva' and 'Kara'. The proximity of neighbouring plants was mimicked by supplemental far-red light treatment of VOC emitter plants of barley grown in growth chambers. Volatiles emitted by 'Alva' under control and far-red light-enriched conditions were analysed using gas chromatography-mass spectrometry (GC-MS). 'Kara' plants were exposed to the VOC blend emitted by the 'Alva' plants that were subjected to either of the light treatments. Dry matter partitioning, leaf area, stem and total root length were determined for 'Kara' plants exposed to 'Alva' VOCs, and also for 'Alva' plants exposed to either control or far-red-enriched light treatments. Total VOC emissions by 'Alva' were reduced under low R:FR conditions compared with control light conditions, although individual volatile compounds were found to be either suppressed, induced or not affected by R:FR. The altered composition of the VOC blend emitted by 'Alva' plants exposed to low R:FR was found to affect carbon allocation in receiver plants of 'Kara'. The results indicate that changes in R:FR light conditions influence the emissions of VOCs in barley, and that these altered emissions affect VOC-mediated plant-plant interactions. © The Author 2015. Published by Oxford University Press on

  14. Early Life Exposure to Fructose Alters Maternal, Fetal and Neonatal Hepatic Gene Expression and Leads to Sex-Dependent Changes in Lipid Metabolism in Rat Offspring.

    Directory of Open Access Journals (Sweden)

    Zoe E Clayton

    Full Text Available Fructose consumption is associated with altered hepatic function and metabolic compromise and not surprisingly has become a focus for perinatal studies. We have previously shown that maternal fructose intake results in sex specific changes in fetal, placental and neonatal outcomes. In this follow-up study we investigated effects on maternal, fetal and neonatal hepatic fatty acid metabolism and immune modulation.Pregnant rats were randomised to either control (CON or high-fructose (FR diets. Fructose was given in solution and comprised 20% of total caloric intake. Blood and liver samples were collected at embryonic day 21 (E21 and postnatal day (P10. Maternal liver samples were also collected at E21 and P10. Liver triglyceride and glycogen content was measured with standard assays. Hepatic gene expression was measured with qPCR.Maternal fructose intake during pregnancy resulted in maternal hepatic ER stress, hepatocellular injury and increased levels of genes that favour lipogenesis. These changes were associated with a reduction in the NLRP3 inflammasome. Fetuses of mothers fed a high fructose diet displayed increased hepatic fructose transporter and reduced fructokinase mRNA levels and by 10 days of postnatal age, also have hepatic ER stress, and elevated IL1β mRNA levels. At P10, FR neonates demonstrated increased hepatic triglyceride content and particularly in males, associated changes in the expression of genes regulating beta oxidation and the NLRP3 inflammasome. Further, prenatal fructose results in sex-dependant changes in levels of key clock genes.Maternal fructose intake results in age and sex-specific alterations in maternal fetal and neonatal free fatty acid metabolism, which may be associated in disruptions in core clock gene machinery. How these changes are associated with hepatic inflammatory processes is still unclear, although suppression of the hepatic inflammasome, as least in mothers and male neonates may point to impaired

  15. Overexpression of miR156 in switchgrass (Panicum virgatum L.) results in various morphological alterations and leads to improved biomass production

    Science.gov (United States)

    Fu, Chunxiang; Sunkar, Ramanjulu; Zhou, Chuanen; Shen, Hui; Zhang, Ji-Yi; Matts, Jessica; Wolf, Jennifer; Mann, David G J; Stewart, C Neal; Tang, Yuhong; Wang, Zeng-Yu

    2012-01-01

    Switchgrass (Panicum virgatum L.) has been developed into a dedicated herbaceous bioenergy crop. Biomass yield is a major target trait for genetic improvement of switchgrass. microRNAs have emerged as a prominent class of gene regulatory factors that has the potential to improve complex traits such as biomass yield. A miR156b precursor was overexpressed in switchgrass. The effects of miR156 overexpression on SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL) genes were revealed by microarray and quantitative RT-PCR analyses. Morphological alterations, biomass yield, saccharification efficiency and forage digestibility of the transgenic plants were characterized. miR156 controls apical dominance and floral transition in switchgrass by suppressing its target SPL genes. Relatively low levels of miR156 overexpression were sufficient to increase biomass yield while producing plants with normal flowering time. Moderate levels of miR156 led to improved biomass but the plants were non-flowering. These two groups of plants produced 58%–101% more biomass yield compared with the control. However, high miR156 levels resulted in severely stunted growth. The degree of morphological alterations of the transgenic switchgrass depends on miR156 level. Compared with floral transition, a lower miR156 level is required to disrupt apical dominance. The improvement in biomass yield was mainly because of the increase in tiller number. Targeted overexpression of miR156 also improved solubilized sugar yield and forage digestibility, and offered an effective approach for transgene containment. PMID:22239253

  16. Image-Guided Analyses Reveal that Non-CD4 Splenocytes Contribute to CD4+ T Cell–Mediated Inflammation Leading to Islet Destruction by Altering Their Local Function and Not Systemic Trafficking Patterns

    Directory of Open Access Journals (Sweden)

    Mi-Heon Lee

    2007-11-01

    Full Text Available Recruitment of CD4+ T cells into islets is a critical component of islet inflammation (insulitis leading to type 1 diabetes; therefore, determining if conditions used to treat diabetes change their trafficking patterns is relevant to the outcome. Cotransfer of CD4+BDC2.5 (BDC cells with non-CD4 splenocytes obtained from newly diabetic NOD mice, but not when they are transferred alone, induces accelerated diabetes. It is unclear whether these splenocytes affect diabetes development by altering the systemic and/or local trafficking and proliferation patterns of BDC cells in target and nontarget tissues. To address these questions, we developed an animal model to visualize BDC cell trafficking and proliferation using whole-body in vivo bioluminescence imaging and used the images to direct tissue sampling for further analyses of the cell distribution within tissues. The whole-body, or macroscopic, trafficking patterns were not dramatically altered in both groups of recipient mice. However, the local patterns of cell distribution were distinct, which led to invasive insulitis only in cotransferred mice with an increased number of islet-infiltrating CD11b+ and CD11c+ cells. Taken together, the non-CD4 splenocytes act locally by promoting invasive insulitis without altering the systemic trafficking patterns or proliferation of BDC cells and thus contributing to diabetes by altering the localization within the tissue.

  17. Deletion of 12/15-lipoxygenase alters macrophage and islet function in NOD-Alox15(null mice, leading to protection against type 1 diabetes development.

    Directory of Open Access Journals (Sweden)

    Shamina M Green-Mitchell

    Full Text Available AIMS: Type 1 diabetes (T1D is characterized by autoimmune depletion of insulin-producing pancreatic beta cells. We showed previously that deletion of the 12/15-lipoxygenase enzyme (12/15-LO, Alox15 gene in NOD mice leads to nearly 100 percent protection from T1D. In this study, we test the hypothesis that cytokines involved in the IL-12/12/15-LO axis affect both macrophage and islet function, which contributes to the development of T1D. METHODS: 12/15-LO expression was clarified in immune cells by qRT-PCR, and timing of expression was tested in islets using qRT-PCR and Western blotting. Expression of key proinflammatory cytokines and pancreatic transcription factors was studied in NOD and NOD-Alox15(null macrophages and islets using qRT-PCR. The two mouse strains were also assessed for the ability of splenocytes to transfer diabetes in an adoptive transfer model, and beta cell mass. RESULTS: 12/15-LO is expressed in macrophages, but not B and T cells of NOD mice. In macrophages, 12/15-LO deletion leads to decreased proinflammatory cytokine mRNA and protein levels. Furthermore, splenocytes from NOD-Alox15(null mice are unable to transfer diabetes in an adoptive transfer model. In islets, expression of 12/15-LO in NOD mice peaks at a crucial time during insulitis development. The absence of 12/15-LO results in maintenance of islet health with respect to measurements of islet-specific transcription factors, markers of islet health, proinflammatory cytokines, and beta cell mass. CONCLUSIONS: These results suggest that 12/15-LO affects islet and macrophage function, causing inflammation, and leading to autoimmunity and reduced beta cell mass.

  18. Loss of Asxl1 Alters Self-Renewal and Cell Fate of Bone Marrow Stromal Cell, Leading to Bohring-Opitz-like Syndrome in Mice.

    Science.gov (United States)

    Zhang, Peng; Xing, Caihong; Rhodes, Steven D; He, Yongzheng; Deng, Kai; Li, Zhaomin; He, Fuhong; Zhu, Caiying; Nguyen, Lihn; Zhou, Yuan; Chen, Shi; Mohammad, Khalid S; Guise, Theresa A; Abdel-Wahab, Omar; Xu, Mingjiang; Wang, Qian-Fei; Yang, Feng-Chun

    2016-06-14

    De novo ASXL1 mutations are found in patients with Bohring-Opitz syndrome, a disease with severe developmental defects and early childhood mortality. The underlying pathologic mechanisms remain largely unknown. Using Asxl1-targeted murine models, we found that Asxl1 global loss as well as conditional deletion in osteoblasts and their progenitors led to significant bone loss and a markedly decreased number of bone marrow stromal cells (BMSCs) compared with wild-type littermates. Asxl1(-/-) BMSCs displayed impaired self-renewal and skewed differentiation, away from osteoblasts and favoring adipocytes. RNA-sequencing analysis revealed altered expression of genes involved in cell proliferation, skeletal development, and morphogenesis. Furthermore, gene set enrichment analysis showed decreased expression of stem cell self-renewal gene signature, suggesting a role of Asxl1 in regulating the stemness of BMSCs. Importantly, re-introduction of Asxl1 normalized NANOG and OCT4 expression and restored the self-renewal capacity of Asxl1(-/-) BMSCs. Our study unveils a pivotal role of ASXL1 in the maintenance of BMSC functions and skeletal development. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Antibiotic treatment of pregnant non-obese diabetic mice leads to altered gut microbiota and intestinal immunological changes in the offspring.

    Science.gov (United States)

    Tormo-Badia, N; Håkansson, Å; Vasudevan, K; Molin, G; Ahrné, S; Cilio, C M

    2014-10-01

    The intestinal microbiota is important for tolerance induction through mucosal immunological responses. The composition of the gut microbiota of an infant is affected by environmental factors such as diet, disease and antibiotic treatment. However, already in utero, these environmental factors can affect the immunological development of the foetus and influence the future gut microbiota of the infant. To investigate the effects of antibiotic treatment of pregnant mothers on the offspring's gut microbiome and diabetes development, we treated non-obese diabetic (NOD) mice with a cocktail of antibiotics during gestation and the composition of the gut microbiota, diabetes incidence and major gut-related T lymphocyte populations were investigated in the offspring. We observed a persistent reduction in the general diversity of the gut microbiota in the offspring from NOD mothers treated with antibiotics during gestation compared with offspring from control mothers. In addition, by clustering the present bacterial taxa with principal component analysis, we found a differential clustering of gut microbiota in the offspring from NOD mothers treated with antibiotics during gestation compared with offspring from control mothers. Offspring from NOD mothers treated with antibiotics during gestation also showed some immunological alterations in the gut immune system, which could be related to the diversity of the gut microbiome and influence modulation of diabetes development at 20 weeks. Our data point out maternal derangement of the intestinal microbiota as a potential environmental risk factor for T1D development. © 2014 John Wiley & Sons Ltd.

  20. Humoral immune alterations caused by lead: studies on an adult toad model Alteraciones inmunes humorales causadas por plomo: estudios en un modelo de sapo adulto

    Directory of Open Access Journals (Sweden)

    Carolina E. Rosenberg

    2007-07-01

    Full Text Available There is evidence that environmental metal levels affect the immune function. In the particular case of the impact of heavy metals, information available suggests that the immune system is a target for low-dose Pb exposure. Among vertebrates it was shown that amphibians are capable of forming antibodies against a variety of antigens, causing several responses such as anaphylactic response and rejecting grafts. In this study, the production of antibodies was assessed against sheep red blood cells (SRBC in the anuran Bufo arenarum after six weekly injections of sublethal doses of lead (50 mg.kg-1, as lead acetate. Natural antibodies (natural heteroagglutinins were also quantified against SRBC. Both assessments were carried out employing an ELISA method developed to this end, measuring absorbance (A. For natural anti-SRBC antibodies in both control (C and Pb treated (T toads, there was a non significant tendency to increase the initial absorbances (C initial: 0.69±0.39 A; T initial: 0.54±0.30 A, relative to those registered at the end of the experiments (C final: 0.89±0.49 A; T final: 0.76±0.31A; the T/C ratios also did not show changes. The only significant difference was found between initial and final samples from lead-treated toads (pExiste evidencia de que los niveles de metal ambientales afectan la función inmune. En el caso particular del impacto de metales pesados, la información disponible sugiere que el sistema inmune es un blanco para la exposición a bajas dosis de Pb. Entre los vertebrados, se ha mostrado que los anfibios son capaces de formar anticuerpos contra una variedad de antígenos, que causan diversas respuestas, tales como respuesta anafiláctica y rechazo de injertos. En este estudio, la producción de anticuerpos fue evaluada contra eritrocitos de oveja (EO en el anuro Bufo arenarum, luego de seis inyecciones semanales de dosis subletales de plomo (50 mg.kg-1, como acetato de Pb. Los anticuerpos naturales

  1. Matrix Metalloproteinase Stromelysin-1 Triggers a Cascade of Molecular Alterations that leads to stable epithelial-to-Mesenchymal Conversion and a Premalignant Phenotype in Mammary Epithelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Lochter, A.; Galosy, S.; Muschler, J.; Freedman, N.; Werb, Z.; Bissell, M.J.

    1997-08-11

    Matrix metalloproteinases (MMPs) regulate ductal morphogenesis, apoptosis, and neoplastic progression in mammary epithelial cells. To elucidate the direct effects of MMPs on mammary epithelium, we generated functionally normal cells expressing an inducible autoactivating stromelysin-1 (SL-1) transgene. Induction of SL-1 expression resulted in cleavage of E-cadherin, and triggered progressive phenotypic conversion characterized by disappearance of E-cadherin and catenins from cell-cell contacts, downregulation of cytokeratins, upregulation of vimentin, induction of keratinocyte growth factor expression and activation, and upregulation of endogenous MMPs. Cells expressing SL-1 were unable to undergo lactogenic differentiation and became invasive. Once initiated, this phenotypic conversion was essentially stable, and progressed even in the absence of continued SL-1 expression. These observations demonstrate that inappropriate expression of SL-1 initiates a cascade of events that may represent a coordinated program leading to loss of the differentiated epithelial phenotype and gain of some characteristics of tumor cells. Our data provide novel insights into how MMPs function in development and neoplastic conversion.

  2. Chronic ingestion of cadmium and lead alters the bioavailability of essential and heavy metals, gene expression pathways and genotoxicity in mouse intestine.

    Science.gov (United States)

    Breton, Jérôme; Le Clère, Kelly; Daniel, Catherine; Sauty, Mathieu; Nakab, Lauren; Chassat, Thierry; Dewulf, Joëlle; Penet, Sylvie; Carnoy, Christophe; Thomas, Patrick; Pot, Bruno; Nesslany, Fabrice; Foligné, Benoît

    2013-10-01

    Chronic ingestion of environmental heavy metals such as lead (Pb) and cadmium (Cd) causes various well-documented pathologies in specific target organs following their intestinal absorption and subsequent accumulation. However, little is known about the direct impact of the non-absorbed heavy metals on the small intestine and the colon homeostasis. The aim of our study was to compare the specific bioaccumulation and retention of Cd and Pb and their effect on the essential metal balance in primary organs, with those occurring specifically in the gastrointestinal tract of mice. Various doses of Cd (5, 20 and 100 mg l(-1)) and Pb (100 and 500 mg l(-1)) chloride salts were provided in drinking water for subchronic to chronic exposures (4, 8 and 12 weeks). In contrast to a clear dose- and time-dependent accumulation in target organs, results showed that intestines are poor accumulators for Cd and Pb. Notwithstanding, changes in gene expression of representative intestinal markers revealed that the transport-, oxidative- and inflammatory status of the gut epithelium of the duodenum, ileum and colon were specifically affected by both heavy metal species. Additionally, in vivo comet assay used to evaluate the impact of heavy metals on DNA damage showed clear genotoxic activities of Cd, on both the upper and distal parts of the gastrointestinal tract. Altogether, these results outline the resilience of the gut which balances the various effects of chronic Cd and Pb in the intestinal mucosa. Collectively, it provides useful information for the risk assessment of heavy metals in gut homeostasis and further disease's susceptibility.

  3. Maternal obesity programs reduced leptin signaling in the pituitary and altered GH/IGF1 axis function leading to increased adiposity in adult sheep offspring.

    Science.gov (United States)

    Tuersunjiang, Nuermaimaiti; Odhiambo, John F; Shasa, Desiree R; Smith, Ashley M; Nathanielsz, Peter W; Ford, Stephen P

    2017-01-01

    Studies in rodents highlight a role for leptin in stimulation of pituitary growth hormone (GH) secretion, with an impact on body composition regulation. We have reported that maternal obesity (MO) during ovine pregnancy results in hyperphagia, glucose-insulin dysregulation, increased adiposity, hypercortisolemia and hyperleptinemia in mature offspring subjected to a bout of ad libitum feeding. We hypothesized that MO reduces leptin signaling in the pituitary and down regulates the GH/IGF1 axis and increases circulating cortisol leading to increased adiposity in their adult offspring. Male lambs born to MO (n = 6) or control (CON, n = 6) ewes were fed only to requirements until placed on a 12 week ad libitum feeding trial at maturity. The pituitary, hypothalamic arcuate nucleus, and liver were collected at necropsy and mRNA and protein expression determined. Plasma cortisol concentrations were increased (P<0.05) in MO vs. CON offspring at the end of the feeding trial. Further, serum concentrations of IGF1 decreased (P<0.01) and GH tended to decrease (P<0.08) in MO vs. CON offspring. Pituitary mRNA and leptin receptor protein expression were decreased in MO vs. CON offspring in association with decreased GH mRNA expression, and decreased IGF1 mRNA and protein expression in liver. Liver 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) expression was increased (P<0.01) and its cofactor hexose-6-phosphate dehydrogenase tended to increase (P<0.06) in MO vs. CON offspring. 11βHSD2 expression remained unchanged. These data indicate that MO induced an increase in liver conversion of cortisone to cortisol in adult offspring and support a role for leptin signaling in the pituitary in mediating offspring adiposity.

  4. Kresoxim-methyl primes Medicago truncatula plants against abiotic stress factors via altered reactive oxygen and nitrogen species signalling leading to downstream transcriptional and metabolic readjustment.

    Science.gov (United States)

    Filippou, Panagiota; Antoniou, Chrystalla; Obata, Toshihiro; Van Der Kelen, Katrien; Harokopos, Vaggelis; Kanetis, Loukas; Aidinis, Vassilis; Van Breusegem, Frank; Fernie, Alisdair R; Fotopoulos, Vasileios

    2016-03-01

    Biotic and abiotic stresses, such as fungal infection and drought, cause major yield losses in modern agriculture. Kresoxim-methyl (KM) belongs to the strobilurins, one of the most important classes of agricultural fungicides displaying a direct effect on several plant physiological and developmental processes. However, the impact of KM treatment on salt and drought stress tolerance is unknown. In this study we demonstrate that KM pre-treatment of Medicago truncatula plants results in increased protection to drought and salt stress. Foliar application with KM prior to stress imposition resulted in improvement of physiological parameters compared with stressed-only plants. This protective effect was further supported by increased proline biosynthesis, modified reactive oxygen and nitrogen species signalling, and attenuation of cellular damage. In addition, comprehensive transcriptome analysis identified a number of transcripts that are differentially accumulating in drought- and salinity-stressed plants (646 and 57, respectively) after KM pre-treatment compared with stressed plants with no KM pre-treatment. Metabolomic analysis suggests that the priming role of KM in drought- and to a lesser extent in salinity-stressed plants can be attributed to the regulation of key metabolites (including sugars and amino acids) resulting in protection against abiotic stress factors. Overall, the present study highlights the potential use of this commonly used fungicide as a priming agent against key abiotic stress conditions. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  5. Bi-allelic Alterations in AEBP1 Lead to Defective Collagen Assembly and Connective Tissue Structure Resulting in a Variant of Ehlers-Danlos Syndrome

    KAUST Repository

    Blackburn, Patrick R.

    2018-03-29

    AEBP1 encodes the aortic carboxypeptidase-like protein (ACLP) that associates with collagens in the extracellular matrix (ECM) and has several roles in development, tissue repair, and fibrosis. ACLP is expressed in bone, the vasculature, and dermal tissues and is involved in fibroblast proliferation and mesenchymal stem cell differentiation into collagen-producing cells. Aebp1 mice have abnormal, delayed wound repair correlating with defects in fibroblast proliferation. In this study, we describe four individuals from three unrelated families that presented with a unique constellation of clinical findings including joint laxity, redundant and hyperextensible skin, poor wound healing with abnormal scarring, osteoporosis, and other features reminiscent of Ehlers-Danlos syndrome (EDS). Analysis of skin biopsies revealed decreased dermal collagen with abnormal collagen fibrils that were ragged in appearance. Exome sequencing revealed compound heterozygous variants in AEBP1 (c.1470delC [p.Asn490_Met495delins(40)] and c.1743C>A [p.Cys581]) in the first individual, a homozygous variant (c.1320_1326del [p.Arg440Serfs3]) in the second individual, and a homozygous splice site variant (c.1630+1G>A) in two siblings from the third family. We show that ACLP enhances collagen polymerization and binds to several fibrillar collagens via its discoidin domain. These studies support the conclusion that biallelic pathogenic variants in AEBP1 are the cause of this autosomal-recessive EDS subtype.

  6. The impact of auxins used in assisted phytoextraction of metals from the contaminated environment on the alterations caused by lead(II) ions in the organization of model lipid membranes.

    Science.gov (United States)

    Hąc-Wydro, Katarzyna; Sroka, Aleksandra; Jabłońska, Klaudia

    2016-07-01

    Auxins are successfully used to improve phytoextraction efficiency of metal ions from the contaminated environment, however, the mechanism of their activity in this field is not explained. Auxins are known to exert various biochemical alterations in the plant membranes and cells, but their activity involves also direct interactions with lipids leading to changes in membrane organization. Following the suggestion that the auxins-induced modifications in membrane properties alleviate toxic effect of metal ions in this paper we have undertaken the comparative studies on the effect of metal ions and metal ions/auxins mixtures on model membrane systems. The experiments were done on lipid monolayers differing in their composition spread on water subphase and on Pb(2+), Indole-3-acetic acid (IAA), 1-Naphthaleneacetic acid (NAA) and Pb(2+)/IAA and Pb(2+)/NAA water solutions. The analysis of the collected data suggests that metal ions and auxins can change fluidity of the lipid systems and weaken the interactions between monolayer components. This manifested in the increase of the mean area per molecule and the excess area per molecule values for the films on Pb(2+), auxins as well as Pb(2+)/auxin solutions as compared to the values on pure water subphase. However, the presence of auxin in the mixture with lead(II) ions makes the alterations induced by sole metal ions weaker. This effect was more pronounced for the membranes of a higher packing. Thus it was proposed that auxins may enhance phytoextraction of metal ions by weakening their destabilizing effect on membrane. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Cultivation of Staphylococcus epidermidis in the Human Spaceflight Environment Leads to Alterations in the Frequency and Spectrum of Spontaneous Rifampicin-Resistance Mutations in the rpoB Gene.

    Science.gov (United States)

    Fajardo-Cavazos, Patricia; Nicholson, Wayne L

    2016-01-01

    Bacteria of the genus Staphylococcus are persistent inhabitants of human spaceflight habitats and represent potential opportunistic pathogens. The effect of the human spaceflight environment on the growth and the frequency of mutations to antibiotic resistance in the model organism Staphylococcus epidermidis strain ATCC12228 was investigated. Six cultures of the test organism were cultivated in biological research in canisters-Petri dish fixation units for 122 h on orbit in the International Space Station (ISS) as part of the SpaceX-3 resupply mission. Asynchronous ground controls (GCs) consisted of identical sets of cultures cultivated for 122 h in the ISS Environmental Simulator at Kennedy Space Center. S. epidermidis exhibited significantly lower viable counts but significantly higher frequencies of mutation to rifampicin (Rif) resistance in space vs. GC cultures. The spectrum of mutations in the rpoB gene leading to Rif(R) was altered in S. epidermidis isolates cultivated in the ISS compared to GCs. The results suggest that the human spaceflight environment induces unique physiologic stresses on growing bacterial cells leading to changes in mutagenic potential.

  8. Smectite alteration

    International Nuclear Information System (INIS)

    Anderson, D.M.

    1984-11-01

    This report contains the proceedings of a second workshop in Washington DC December 8-9, 1983 on the alteration of smectites intended for use as buffer materials in the long-term containment of nuclear wastes. It includes extended summaries of all presentations and a transcript of the detailed scientific discussion. The discussions centered on three main questions: What is the prerequisite for and what is the precise mechanism by which smectite clays may be altered to illite. What are likly sources of potassium with respect to the KBS project. Is it likely that the conversion of smectite to illite will be of importance in the 10 5 to the 10 6 year time frame. The workshop was convened to review considerations and conclusions in connection to these questions and also to broaden the discussion to consider the use of smectite clays as buffer materials for similar applications in different geographical and geological settings. SKBF/KBS technical report 83-03 contains the proceedings from the first workshop on these matters that was held at the State University of New York, Buffalo May 26-27, 1982. (Author)

  9. Developmental immunotoxicology of lead

    International Nuclear Information System (INIS)

    Dietert, Rodney R.; Lee, Ji-Eun; Hussain, Irshad; Piepenbrink, Michael

    2004-01-01

    The heavy metal, lead, is a known developmental immunotoxicant that has been shown to produce immune alterations in humans as well as other species. Unlike many compounds that exert adverse immune effects, lead exposure at low to moderate levels does not produce widespread loss of immune cells. In contrast, changes resulting from lead exposure are subtle at the immune cell population level but, nevertheless, can be functionally dramatic. A hallmark of lead-induced immunotoxicity is a pronounced shift in the balance in T helper cell function toward T helper 2 responses at the expense of T helper 1 functions. This bias alters the nature and range of immune responses that can be produced thereby influencing host susceptibility to various diseases. Immunotoxic responses to lead appear to differ across life stages not only quantitatively with regard to dose response, but also qualitatively in terms of the spectrum of immune alterations. Experimental studies in several lab animal species suggest the latter stages of gestation are a period of considerable sensitivity for lead-induced immunotoxicity. This review describes the basic characteristics of lead-induced immunotoxicity emphasizing experimental animal results. It also provides a framework for the consideration of toxicant exposure effects across life stages. The existence of and probable basis for developmental windows of immune hyper-susceptibility are presented. Finally, the potential for lead to serve as a perinatal risk factor for childhood asthma as well as other diseases is considered

  10. Lead Poisoning

    Science.gov (United States)

    Lead is a metal that occurs naturally in the earth's crust. Lead can be found in all parts of our ... from human activities such as mining and manufacturing. Lead used to be in paint; older houses may ...

  11. Lead Toxicity

    Science.gov (United States)

    ... time may lead to reduced IQ, slow learning, Attention Deficit Hyperactivity Disorder (ADHD), or behavioral issues. • Lead also affects other parts ... 800-424-5323) • U.S. Environmental Protection Agency Lead Awareness Program http: / / www. epa. gov/ lead • EPA publication “ ...

  12. Epigenetic-based combinatorial resveratrol and pterostilbene alters DNA damage response by affecting SIRT1 and DNMT enzyme expression, including SIRT1-dependent γ-H2AX and telomerase regulation in triple-negative breast cancer

    International Nuclear Information System (INIS)

    Kala, Rishabh; Shah, Harsh N.; Martin, Samantha L.; Tollefsbol, Trygve O.

    2015-01-01

    Nutrition is believed to be a primary contributor in regulating gene expression by affecting epigenetic pathways such as DNA methylation and histone modification. Resveratrol and pterostilbene are phytoalexins produced by plants as part of their defense system. These two bioactive compounds when used alone have been shown to alter genetic and epigenetic profiles of tumor cells, but the concentrations employed in various studies often far exceed physiologically achievable doses. Triple-negative breast cancer (TNBC) is an often fatal condition that may be prevented or treated through novel dietary-based approaches. HCC1806 and MDA-MB-157 breast cancer cells were used as TNBC cell lines in this study. MCF10A cells were used as control breast epithelial cells to determine the safety of this dietary regimen. CompuSyn software was used to determine the combination index (CI) for drug combinations. Combinatorial resveratrol and pterostilbene administered at close to physiologically relevant doses resulted in synergistic (CI <1) growth inhibition of TNBCs. SIRT1, a type III histone deacetylase (HDAC), was down-regulated in response to this combinatorial treatment. We further explored the effects of this novel combinatorial approach on DNA damage response by monitoring γ-H2AX and telomerase expression. With combination of these two compounds there was a significant decrease in these two proteins which might further resulted in significant growth inhibition, apoptosis and cell cycle arrest in HCC1806 and MDA-MB-157 breast cancer cells, while there was no significant effect on cellular viability, colony forming potential, morphology or apoptosis in control MCF10A breast epithelial cells. SIRT1 knockdown reproduced the effects of combinatorial resveratrol and pterostilbene-induced SIRT1 down-regulation through inhibition of both telomerase activity and γ-H2AX expression in HCC1806 breast cancer cells. As a part of the repair mechanisms and role of SIRT1 in recruiting DNMTs

  13. Lead and tap water

    Science.gov (United States)

    Water contaminated with lead ... The Environmental Protection Agency (EPA) monitors drinking water in the United States. It requires water suppliers to produce annual water quality reports. These reports include information about lead amounts, and they ...

  14. Anatomy of lead poisoning

    African Journals Online (AJOL)

    ABEOLUGBENGAS

    Abstract. Objective: Lead poisoning and lead toxicity is usually often interchangeably used by different Scientists. The Anatomy of lead poisoning encompasses its effects on different organ-systems of different species of organisms. It also includes environmental, functional and biochemical components associated with most.

  15. Lead poisoning

    Science.gov (United States)

    ... help if this information is not immediately available. Poison Control If someone has severe symptoms from possible ... be caused by lead poisoning, call your local poison control center. Your local poison center can be ...

  16. Lead in the environment

    Science.gov (United States)

    Pattee, Oliver H.; Pain, Deborah J.; Hoffman, David J.; Rattner, Barnett A.; Burton, G. Allen; Cairns, John

    2003-01-01

    Anthropogenic uses of lead have probably altered its availability and environmental distribution more than any other toxic element. Consequently, lead concentrations in many living organisms may be approaching thresholds of toxicity for the adverse effects of lead. Such thresholds are difficult to define, as they vary with the chemical and physical form of lead, exposure regime, other elements present and also vary both within and between species. The technological capability to accurately quantify low lead concentrations has increased over the last decade, and physiological and behavioral effects have been measured in wildlife with tissue lead concentrations below those previously considered safe for humans.s.236 Consequently. lead criteria for the protection of wildlife and human health are frequently under review, and 'thresholds' of lead toxicity are being reconsidered. Proposed lead criteria for the protection of natural resources have been reviewed by Eisler. Uptake of lead by plants is limited by its generally low availability in soils and sediments, and toxicity may be limited by storage mechanisms and its apparently limited translocation within most plants. Lead does not generally accumulate within the foliar parts of plants, which limits its transfer to higher trophic levels. Although lead may concentrate in plant and animal tissues, no evidence of biomagnification exists. Acid deposition onto surface waters and soils with low buffering capacity may influence the availability of lead for uptake by plants and animals, and this may merit investigation at susceptible sites. The biological significance of chronic low-level lead exposure to wildlife is sometimes difficult to quantify. Animals living in urban environments or near point sources of lead emission are inevitably subject to greater exposure to lead and enhanced risk of lead poisoning. Increasingly strict controls on lead emissions in many countries have reduced exposure to lead from some sources

  17. Ecotoxicology: Lead

    Science.gov (United States)

    Scheuhammer, A.M.; Beyer, W.N.; Schmitt, C.J.; Jorgensen, Sven Erik; Fath, Brian D.

    2008-01-01

    Lead (Pb) is a naturally occurring metallic element; trace concentrations are found in all environmental media and in all living things. However, certain human activities, especially base metal mining and smelting; combustion of leaded gasoline; the use of Pb in hunting, target shooting, and recreational angling; the use of Pb-based paints; and the uncontrolled disposal of Pb-containing products such as old vehicle batteries and electronic devices have resulted in increased environmental levels of Pb, and have created risks for Pb exposure and toxicity in invertebrates, fish, and wildlife in some ecosystems.

  18. Lead grids

    CERN Multimedia

    1974-01-01

    One of the 150 lead grids used in the multiwire proportional chamber g-ray detector. The 0.75 mm diameter holes are spaced 1 mm centre to centre. The grids were made by chemical cutting techniques in the Godet Workshop of the SB Physics.

  19. Leading men

    DEFF Research Database (Denmark)

    Bekker-Nielsen, Tønnes

    2016-01-01

    Through a systematic comparison of c. 50 careers leading to the koinarchate or high priesthood of Asia, Bithynia, Galatia, Lycia, Macedonia and coastal Pontus, as described in funeral or honorary inscriptions of individual koinarchs, it is possible to identify common denominators but also disting...

  20. Properties of myelin altered peptide ligand cyclo(87-99)(Ala91,Ala96)MBP87-99 render it a promising drug lead for immunotherapy of multiple sclerosis.

    Science.gov (United States)

    Deraos, George; Rodi, Maria; Kalbacher, Hubert; Chatzantoni, Kokona; Karagiannis, Fotios; Synodinos, Loukas; Plotas, Panayiotis; Papalois, Apostolos; Dimisianos, Nikolaos; Papathanasopoulos, Panagiotis; Gatos, Dimitrios; Tselios, Theodore; Apostolopoulos, Vasso; Mouzaki, Athanasia; Matsoukas, John

    2015-08-28

    Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system, and it has been established that autoreactive T helper (Th) cells play a crucial role in its pathogenesis. Myelin basic protein (MBP) epitopes are major autoantigens in MS, and the sequence MBP87-99 is an immunodominant epitope. We have previously reported that MBP87-99 peptides with modifications at principal T-cell receptor (TCR) contact sites suppressed the induction of EAE symptoms in rats and SJL/J mice, diverted the immune response from Th1 to Th2 and generated antibodies that did not cross react with the native MBP protein. In this study, the linear and cyclic analogs of the MBP87-99 epitope, namely linear (Ala91,Ala96)MBP87-99 (P2) and cyclo(87-99)(Ala91,Ala96)MBP87-99 (P3), were evaluated for their binding to HLA-DR4, stability to lysosomal enzymes, their effect on cytokine secretion by peripheral blood mononuclear cells (PBMC) derived from MS patients or healthy subjects (controls), and their effect in rat EAE. P1 peptide (wild-type, MBP87-99) was used as control. P2 and P3 did not alter significantly the cytokine secretion by control PBMC, in contrast to P1 that induced moderate IL-10 production. In MS PBMC, P2 and P3 induced the production of IL-2 and IFN-γ, with a simultaneous decrease of IL-10, whereas P1 caused a reduction of IL-10 secretion only. The cellular response to P3 indicated that cyclization did not affect the critical TCR contact sites in MS PBMC. Interestingly, the cyclic P3 analog was found to be a stronger binder to HLA-DR4 compared to linear P2. Moreover, cyclic P3 was more stable to proteolysis compared to linear P2. Finally, both P2 and P3 suppressed EAE induced by an encephalitogenic guinea pig MBP74-85 epitope in Lewis rats whereas P1 failed to do so. In conclusion, cyclization of myelin altered peptide ligand (Ala91,Ala96)MBP87-99 improved binding affinity to HLA-DR4, resistance to proteolysis and antigen-specific immunomodulation

  1. Cellular and molecular toxicity of lead in bone

    Energy Technology Data Exchange (ETDEWEB)

    Pounds, J.G. (Wayne State Univ., Detroit, MI (United States)); Long, G.J.; Rosen, J.F. (Albert Einstein College of Medicine, Bronx, NY (United States))

    1991-02-01

    To fully understand the significance of bone as a target tissue of lead toxicity, as well as a reservoir of systemic lead, it is necessary to define the effects of lead on the cellular components of bone. Skeletal development and the regulation of skeletal mass are ultimately determined by the four different types of cells: osteoblasts, lining cells, osteoclasts, and osteocytes. These cells, which line and penetrate the mineralized matrix, are responsible for matrix formation, mineralization, and bone resorption, under the control of both systemic and local factors. Systemic components of regulation include parathyroid hormone, 1,25-dihydroxyvitamin D{sub 3}, and calcitonin; local regulators include numerous cytokines and growth factors. Lead intoxication directly alters many aspects of bone cell function. First, lead may indirectly alter bone cell function through changes in the circulating levels of those hormones, particularly 1,25-dihydroxyvitamin D{sub 3}, which modulate bone cell function. Second, lead may directly alter bone cell function by perturbing the ability of bone cells to respond to hormonal regulation. Third, lead may impair the ability of cells to synthesize or secrete other components of the bone matrix, such as collagen or bone sialoproteins (osteopontin). Finally, lead may directly effect of substitute for calcium in the active sites of the calcium messenger system. The effects of lead on the recruitment and differentiation of bone cells remains to be established. Many of the toxic effects of lead on bone cell function may be produced by perturbation of the calcium and cAMP messenger systems in these cells.

  2. Lead-Free Piezoelectrics

    CERN Document Server

    Nahm, Sahn

    2012-01-01

    Ecological restrictions in many parts of the world are demanding the elimination of Pb from all consumer items. At this moment in the piezoelectric ceramics industry, there is no issue of more importance than the transition to lead-free materials. The goal of Lead-Free Piezoelectrics is to provide a comprehensive overview of the fundamentals and developments in the field of lead-free materials and products to leading researchers in the world. The text presents chapters on demonstrated applications of the lead-free materials, which will allow readers to conceptualize the present possibilities and will be useful for both students and professionals conducting research on ferroelectrics, piezoelectrics, smart materials, lead-free materials, and a variety of applications including sensors, actuators, ultrasonic transducers and energy harvesters.

  3. Radiation alters PD-L1/NKG2D ligand levels in lung cancer cells and leads to immune escape from NK cell cytotoxicity via IL-6-MEK/Erk signaling pathway.

    Science.gov (United States)

    Shen, Ming Jing; Xu, Li Jun; Yang, Li; Tsai, Ying; Keng, Peter C; Chen, Yongbing; Lee, Soo Ok; Chen, Yuhchyau

    2017-10-06

    We investigated whether radiation influences the susceptibility of non-small cell lung cancer (NSCLC) cells to NK cell mediated cytotoxicity. We found radiation treatment increased expression of programmed cell death ligand 1 (PD-L1), but decreased NK group 2, member D (NKG2D) ligand expressions in A549 and H157 NSCLC cells. Both types of changes would have protected tumor cells from the cytotoxic action of NK cells. Consistently, we detected similar alteration in these molecules in radioresistant A549R26-1 and H157R24-1 subline cells. Higher PD-L1 level was also observed in tumors of A549R26-1 cell-derived xenografts than tumors of parental A549 (A549P) cell-derived xenografts. Accordingly, we found radioresistant cells were more resistant to the cytotoxic action of NK cells than parental cells, and such resistance was decreased when neutralizing antibody (Ab) of PD-L1 was added to the radioresistant cell/NK cell co-cultures. In mechanism studies, we found that IL-6-MEK/Erk signaling contributed most significantly to the up-regulation of PD-L1/down-regulation of NKG2D ligands in radioresistant cells. The addition of the MEK/Erk inhibitor increased the susceptibility of A549R26-1 and H157R24-1 cells to NK-cell cytotoxicity while no significant effect was observed in parental cells. Moreover, we detected enhanced NK-cell cytotoxicity to radioresistant cells when PD-L1 Ab and MEK/Erk inhibitor were added together to co-cultures of tumor/NK cells compared to when PD-L1 Ab was used alone. We suggest that combined use of PD-L1 Ab and MEK/Erk inhibitor may offer better therapeutic benefits than PD-L1 Ab alone to treat NSCLC patients who are receiving radiotherapy or who are at the radioresistant stage.

  4. Radiation alters PD-L1/NKG2D ligand levels in lung cancer cells and leads to immune escape from NK cell cytotoxicity via IL-6-MEK/Erk signaling pathway

    Science.gov (United States)

    Shen, Ming Jing; Xu, Li Jun; Yang, Li; Tsai, Ying; Keng, Peter C.; Chen, Yongbing; Lee, Soo Ok; Chen, Yuhchyau

    2017-01-01

    We investigated whether radiation influences the susceptibility of non-small cell lung cancer (NSCLC) cells to NK cell mediated cytotoxicity. We found radiation treatment increased expression of programmed cell death ligand 1 (PD-L1), but decreased NK group 2, member D (NKG2D) ligand expressions in A549 and H157 NSCLC cells. Both types of changes would have protected tumor cells from the cytotoxic action of NK cells. Consistently, we detected similar alteration in these molecules in radioresistant A549R26-1 and H157R24-1 subline cells. Higher PD-L1 level was also observed in tumors of A549R26-1 cell-derived xenografts than tumors of parental A549 (A549P) cell-derived xenografts. Accordingly, we found radioresistant cells were more resistant to the cytotoxic action of NK cells than parental cells, and such resistance was decreased when neutralizing antibody (Ab) of PD-L1 was added to the radioresistant cell/NK cell co-cultures. In mechanism studies, we found that IL-6-MEK/Erk signaling contributed most significantly to the up-regulation of PD-L1/down-regulation of NKG2D ligands in radioresistant cells. The addition of the MEK/Erk inhibitor increased the susceptibility of A549R26-1 and H157R24-1 cells to NK-cell cytotoxicity while no significant effect was observed in parental cells. Moreover, we detected enhanced NK-cell cytotoxicity to radioresistant cells when PD-L1 Ab and MEK/Erk inhibitor were added together to co-cultures of tumor/NK cells compared to when PD-L1 Ab was used alone. We suggest that combined use of PD-L1 Ab and MEK/Erk inhibitor may offer better therapeutic benefits than PD-L1 Ab alone to treat NSCLC patients who are receiving radiotherapy or who are at the radioresistant stage. PMID:29113321

  5. Poor maternal nutrition leads to alterations in oxidative stress, antioxidant defense capacity, and markers of fibrosis in rat islets: potential underlying mechanisms for development of the diabetic phenotype in later life.

    Science.gov (United States)

    Tarry-Adkins, Jane L; Chen, Jian-Hua; Jones, Richard H; Smith, Noel H; Ozanne, Susan E

    2010-08-01

    Low birth weight is associated with glucose intolerance, insulin resistance, and type 2 diabetes (T2D) in later life. Good evidence indicates that the environment plays an important role in this relationship. However, the mechanisms underlying these relationships are defined poorly. Islets are particularly susceptible to oxidative stress, and this condition combined with fibrosis is thought to be instrumental in T2D pathogenesis. Here we use our maternal low-protein (LP) rat model to determine the effect of early diet on oxidative stress and fibrosis in pancreatic islets of male offspring at 3 and 15 mo of age. Islet xanthine oxidase (XO) expression was increased in 15-mo LP offspring, which suggests increased oxidative-stress. Manganese superoxide-dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), and heme oxygenase-1 (HO-1) (antioxidant enzymes) were reduced significantly in LP offspring, which indicated impairment of oxidative defense. Expression of fibrosis markers collagen I and collagen III also increased in 15-mo LP offspring. Angiotensin II receptor type I (AT(II)R(1)), induced by hyperglycemia and oxidative-stress, was significantly up-regulated in 15-mo LP offspring. Lipid peroxidation was also increased in 15-mo LP animals. We conclude that maternal protein restriction causes age-associated increased oxidative stress, impairment of oxidative defense, and fibrosis. These findings provide mechanisms by which suboptimal early nutrition can lead to T2D development later in life.

  6. Penetration of the signal sequence of Escherichia coli PhoE protein into phospholipid model membranes leads to lipid-specific changes in signal peptide structure and alterations of lipid organization

    International Nuclear Information System (INIS)

    Batenburg, A.M.; Demel, R.A.; Verkleij, A.J.; de Kruijff, B.

    1988-01-01

    In order to obtain more insight in the initial steps of the process of protein translocation across membranes, biophysical investigations were undertaken on the lipid specificity and structural consequences of penetration of the PhoE signal peptide into lipid model membranes and on the conformation of the signal peptide adopted upon interaction with the lipids. When the monolayer technique and differential scanning calorimetry are used, a stronger penetration is observed for negatively charged lipids, significantly influenced by the physical state of the lipid but not by temperature or acyl chain unsaturation as such. Although the interaction is principally electrostatic, as indicated also by the strong penetration of N-terminal fragments into negatively charged lipid monolayers, the effect of ionic strength suggests an additional hydrophobic component. Most interestingly with regard to the mechanism of protein translocation, the molecular area of the peptide in the monolayer also shows lipid specificity: the area in the presence of PC is consistent with a looped helical orientation, whereas in the presence of cardiolipin a time-dependent conformational change is observed, most likely leading from a looped to a stretched orientation with the N-terminus directed toward the water. This is in line also with the determined peptide-lipid stoichiometry. Preliminary 31 P NMR and electron microscopy data on the interaction with lipid bilayer systems indicate loss of bilayer structure

  7. PEDF-induced alteration of metabolism leading to insulin resistance.

    Science.gov (United States)

    Carnagarin, Revathy; Dharmarajan, Arunasalam M; Dass, Crispin R

    2015-02-05

    Pigment epithelium-derived factor (PEDF) is an anti-angiogenic, immunomodulatory, and neurotrophic serine protease inhibitor protein. PEDF is evolving as a novel metabolic regulatory protein that plays a causal role in insulin resistance. Insulin resistance is the central pathogenesis of metabolic disorders such as obesity, type 2 diabetes mellitus, polycystic ovarian disease, and metabolic syndrome, and PEDF is associated with them. The current evidence suggests that PEDF administration to animals induces insulin resistance, whereas neutralisation improves insulin sensitivity. Inflammation, lipolytic free fatty acid mobilisation, and mitochondrial dysfunction are the proposed mechanism of PEDF-mediated insulin resistance. This review summarises the probable mechanisms adopted by PEDF to induce insulin resistance, and identifies PEDF as a potential therapeutic target in ameliorating insulin resistance. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Altering hemodynamics leads to congenital heart defects (Conference Presentation)

    Science.gov (United States)

    Ford, Stephanie M.; McPheeters, Matthew T.; Wang, Yves T.; Gu, Shi; Doughman, Yong Qiu; Strainic, James P.; Rollins, Andrew M.; Watanabe, Michiko; Jenkins, Michael W.

    2016-03-01

    The role of hemodynamics in early heart development is poorly understood. In order to successfully assess the impact of hemodynamics on development, we need to monitor and perturb blood flow, and quantify the resultant effects on morphology. Here, we have utilized cardiac optical pacing to create regurgitant flow in embryonic hearts and OCT to quantify regurgitation percentage and resultant morphology. Embryonic quail in a shell-less culture were optically paced at 3 Hz (well above the intrinsic rate or 1.33-1.67 Hz) on day 2 of development (3-4 weeks human) for 5 minutes. The pacing fatigued the heart and led to a prolonged period (> 1 hour) of increased regurgitant flow. Embryos were kept alive until day 3 (cardiac looping - 4-5 weeks human) or day 8 (4 chambered heart - 8 weeks human) to quantify resultant morphologic changes with OCT. All paced embryos imaged at day 3 displayed cardiac defects. The extent of regurgitant flow immediately after pacing was correlated with cardiac cushion size 24-hours post pacing (p-value cardio-facial/DiGeorge syndrome models suggesting that hemodynamics plays a role in these syndromes as well. Utilizing OCT and optical pacing to understand hemodynamics in development is an important step towards determining CHD mechanisms and ultimately developing earlier treatments.

  9. Experimental model of lead nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Khalil-Manesh, F.; Gonick, H.C. (Cedars-Sinai Medical Center, Los Angeles, CA (United States)); Cohen, A. (UCLA-Harbor General Hospital, Torrance, CA (United States)); Bergamaschi, E.; Mutti, A. (Univ. of Parma (Italy))

    1992-06-01

    Male Sprague-Dawley rats were exposed to high-dose (0.5%) lead acetate for periods ranging from 1 to 9 months; then lead exposure was discontinued, and animals were sacrificed after 12 months. Two additional groups of low-dose (0.01%) and high-dose (0.5%) rats were exposed to lead for 6 months, then lead was discontinued and the rats were treated with three 5-day courses of 0.5% DMSA (dimercaptosuccinic acid) over the next 6 months. Low-dose lead-treated rats showed no significant pathological changes with or without DMSA treatment, but exhibited a significant increase in GFR after DMSA. High-dose lead-treated animals showed no functional or pathological changes when lead exposure was discontinued after 1 month. However, when duration of exposure was 6 or 9 months, GFR was decreased and serum creatinine and urea nitrogen were increased as compared to controls. Tubulointerstitial disease was severe. Administration of DMSA resulted in an improvement in GFR and a decrease in albuminuria, together with a reduction in size and number of nuclear inclusion bodies in proximal tubules. However, tubulointerstitial scarring was only minimally reduced. It may be concluded that, except for brief initial exposure, discontinuation of high-dose lead exposure fails to reverse lead-induced renal damage. Treatment with the chelator, DMSA, improves renal function but has less effect on pathological alterations. As GFR improved after DMSA treatment in both low-dose and high-dose lead-treated rats, irrespective of the degree of pathological alterations, it may be concluded that the DMSA effect is most likely mediated by hemodynamic changes.

  10. Pump apparatus including deconsolidator

    Energy Technology Data Exchange (ETDEWEB)

    Sonwane, Chandrashekhar; Saunders, Timothy; Fitzsimmons, Mark Andrew

    2014-10-07

    A pump apparatus includes a particulate pump that defines a passage that extends from an inlet to an outlet. A duct is in flow communication with the outlet. The duct includes a deconsolidator configured to fragment particle agglomerates received from the passage.

  11. Optical modulator including grapene

    Science.gov (United States)

    Liu, Ming; Yin, Xiaobo; Zhang, Xiang

    2016-06-07

    The present invention provides for a one or more layer graphene optical modulator. In a first exemplary embodiment the optical modulator includes an optical waveguide, a nanoscale oxide spacer adjacent to a working region of the waveguide, and a monolayer graphene sheet adjacent to the spacer. In a second exemplary embodiment, the optical modulator includes at least one pair of active media, where the pair includes an oxide spacer, a first monolayer graphene sheet adjacent to a first side of the spacer, and a second monolayer graphene sheet adjacent to a second side of the spacer, and at least one optical waveguide adjacent to the pair.

  12. Multi-Omics Reveals that Lead Exposure Disturbs Gut Microbiome Development, Key Metabolites, and Metabolic Pathways.

    Science.gov (United States)

    Gao, Bei; Chi, Liang; Mahbub, Ridwan; Bian, Xiaoming; Tu, Pengcheng; Ru, Hongyu; Lu, Kun

    2017-04-17

    Lead exposure remains a global public health issue, and the recent Flint water crisis has renewed public concern about lead toxicity. The toxicity of lead has been well established in a variety of systems and organs. The gut microbiome has been shown to be highly involved in many critical physiological processes, including food digestion, immune system development, and metabolic homeostasis. However, despite the key role of the gut microbiome in human health, the functional impact of lead exposure on the gut microbiome has not been studied. The aim of this study is to define gut microbiome toxicity induced by lead exposure in C57BL/6 mice using multiomics approaches, including 16S rRNA sequencing, whole genome metagenomics sequencing, and gas chromatography-mass spectrometry (GC-MS) metabolomics. 16S rRNA sequencing revealed that lead exposure altered the gut microbiome trajectory and phylogenetic diversity. Metagenomics sequencing and metabolomics profiling showed that numerous metabolic pathways, including vitamin E, bile acids, nitrogen metabolism, energy metabolism, oxidative stress, and the defense/detoxification mechanism, were significantly disturbed by lead exposure. These perturbed molecules and pathways may have important implications for lead toxicity in the host. Taken together, these results demonstrated that lead exposure not only altered the gut microbiome community structures/diversity but also greatly affected metabolic functions, leading to gut microbiome toxicity.

  13. Epidermal growth factor receptor structural alterations in gastric cancer

    International Nuclear Information System (INIS)

    Moutinho, Cátia; Mateus, Ana R; Milanezi, Fernanda; Carneiro, Fátima; Seruca, Raquel; Suriano, Gianpaolo

    2008-01-01

    EGFR overexpression has been described in many human tumours including gastric cancer. In NSCLC patients somatic EGFR mutations, within the kinase domain of the protein, as well as gene amplification were associated with a good clinical response to EGFR inhibitors. In gastric tumours data concerning structural alterations of EGFR remains controversial. Given its possible therapeutic relevance, we aimed to determine the frequency and type of structural alterations of the EGFR gene in a series of primary gastric carcinomas. Direct sequencing of the kinase domain of the EGFR gene was performed in a series of 77 primary gastric carcinomas. FISH analysis was performed in 30 cases. Association studies between EGFR alterations and the clinical pathological features of the tumours were performed. Within the 77 primary gastric carcinomas we found two EGFR somatic mutations and several EGFR polymorphisms in exon 20. Six different intronic sequence variants of EGFR were also found. Four gastric carcinomas showed balanced polysomy or EGFR gene amplification. We verified that gastric carcinoma with alterations of EGFR (somatic mutations or copy number variation) showed a significant increase of tumour size (p = 0.0094) in comparison to wild-type EGFR carcinomas. We demonstrate that EGFR structural alterations are rare in gastric carcinoma, but whenever present, it leads to tumour growth. We considered that searching for EGFR alterations in gastric cancer is likely to be clinically important in order to identify patients susceptible to respond to tyrosine kinase inhibitors

  14. [Epigenetic alterations in acute lymphoblastic leukemia].

    Science.gov (United States)

    Navarrete-Meneses, María Del Pilar; Pérez-Vera, Patricia

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It is well-known that genetic alterations constitute the basis for the etiology of ALL. However, genetic abnormalities are not enough for the complete development of the disease, and additional alterations such as epigenetic modifications are required. Such alterations, like DNA methylation, histone modifications, and noncoding RNA regulation have been identified in ALL. DNA hypermethylation in promoter regions is one of the most frequent epigenetic modifications observed in ALL. This modification frequently leads to gene silencing in tumor suppressor genes, and in consequence, contributes to leukemogenesis. Alterations in histone remodeling proteins have also been detected in ALL, such as the overexpression of histone deacetylases enzymes, and alteration of acetyltransferases and methyltransferases. ALL also shows alteration in the expression of miRNAs, and in consequence, the modification in the expression of their target genes. All of these epigenetic modifications are key events in the malignant transformation since they lead to the deregulation of oncogenes as BLK, WNT5B and WISP1, and tumor suppressors such as FHIT, CDKN2A, CDKN2B, and TP53, which alter fundamental cellular processes and potentially lead to the development of ALL. Both genetic and epigenetic alterations contribute to the development and evolution of ALL. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  15. Lead content of calcium supplements.

    Science.gov (United States)

    Ross, E A; Szabo, N J; Tebbett, I R

    2000-09-20

    Substantial quantities of lead have been reported in some over-the-counter calcium supplement preparations, including not only bone-meal and dolomite, but also over-the-counter natural and refined calcium carbonate formulations. Examination of this issue is warranted given recent increases in physician recommendations for calcium supplements for prevention and treatment of osteoporosis. To determine the lead content of calcium supplements and to quantify the lead exposure from popular brands of calcium in dosages used for childhood recommended daily allowance, osteoporosis, and phosphate binding in dialysis patients. Analysis of lead content in 21 formulations of nonprescription calcium carbonate (including 7 natural [ie, oyster shell] and 14 refined), 1 brand of prescription-only calcium acetate, and 1 noncalcium synthetic phosphate binder conducted in March 2000. Lead content, assayed using electrothermal atomic absorption, expressed as micrograms of lead per 800 mg/d of elemental calcium, per 1500 mg/d of calcium, and for a range of dosages for patients with renal failure. Six microg/d of lead was considered the absolute dietary limit, with no more than 1 microg/d being the goal for supplements. Four of 7 natural products had measurable lead content, amounting to approximately 1 microg/d for 800 mg/d of calcium, between 1 and 2 microg/d for 1500 mg/d of calcium, and up to 10 microg/d for renal dosages. Four of the 14 refined products had similar lead content, including up to 3 microg/d of lead in osteoporosis calcium dosages and up to 20 microg/d in high renal dosages. No lead was detected in the calcium acetate or polymer products. Lead was present even in some brand name products from major pharmaceutical companies not of natural oyster shell derivation. Despite increasingly stringent limits of lead exposure, many calcium supplement formulations contain lead and thereby may pose an easily avoidable public health concern. JAMA. 2000;284:1425-1429.

  16. Lead poisoning in children.

    Science.gov (United States)

    Dapul, Heda; Laraque, Danielle

    2014-08-01

    There is no safe lead level in children. Primary prevention is the most effective way to bring about the complete removal of lead from the environment and eliminate lead poisoning as a public health concern. The National Lead Information Center can be reached via the Internet at www.epa.gov/lead and www.hud.gov/lead, or via phone at 1-800-424-LEAD (5323).

  17. Systemic dystrophic alterations of skeleton

    International Nuclear Information System (INIS)

    Zedgenidze, G.A.; Kishkovskij, A.N.; Elashov, Yu.G.

    1984-01-01

    A roentgenologic picture of dystrophic alterations of bones following hard, acute and chronic infections diseases, distinct disorders of vitanium balance, diseases of endocrine system, disorder of metabolism and diet, long-term exogenous intoxications including medicinal is given. Distinct dystrophic disorders are characterized both by quantitative and qualitative deviations in physiological change of bones

  18. High temperature superconductor current leads

    Science.gov (United States)

    Hull, John R.; Poeppel, Roger B.

    1995-01-01

    An electrical lead having one end for connection to an apparatus in a cryogenic environment and the other end for connection to an apparatus outside the cryogenic environment. The electrical lead includes a high temperature superconductor wire and an electrically conductive material distributed therein, where the conductive material is present at the one end of the lead at a concentration in the range of from 0 to about 3% by volume, and at the other end of the lead at a concentration of less than about 20% by volume. Various embodiments are shown for groups of high temperature superconductor wires and sheaths.

  19. Learn about Lead

    Science.gov (United States)

    ... and dust-free Clean around painted areas where friction can generate dust, such as doors, windows, and ... Us to ask a question, provide feedback, or report a problem. Lead Lead Home Learn About Lead ...

  20. Lead (Pb) Air Pollution

    Science.gov (United States)

    ... Environmental Protection Agency Search Search Lead (Pb) Air Pollution Contact Us Share As a result of EPA's ... protect aquatic and terrestrial ecosystems. Lead (Pb) Air Pollution Basic Information How does lead get in the ...

  1. Combined processing of lead concentrates

    Science.gov (United States)

    Kubasov, V. L.; Paretskii, V. M.; Sidorin, G. N.; Travkin, V. F.

    2013-06-01

    A combined scheme of processing of lead concentrates with the production of pure metallic lead and the important components containing in these concentrates is considered. This scheme includes sulfating roasting of the lead concentrates and two-stage leaching of the formed cinder with the formation of a sulfate solution and lead sulfate. When transformed into a carbonate form, lead sulfate is used for the production of pure metallic lead. Silver, indium, copper, cadmium, nickel, cobalt, and other important components are separately extracted from a solution. At the last stage, zinc is extracted by either extraction followed by electrolytic extraction of a metal or the return of the forming solution of sulfuric acid to cinder leaching.

  2. Altered Perspectives: Immersive Environments

    Science.gov (United States)

    Shipman, J. S.; Webley, P. W.

    2016-12-01

    Immersive environments provide an exciting experiential technology to visualize the natural world. Given the increasing accessibility of 360o cameras and virtual reality headsets we are now able to visualize artistic principles and scientific concepts in a fully immersive environment. The technology has become popular for photographers as well as designers, industry, educational groups, and museums. Here we show a sci-art perspective on the use of optics and light in the capture and manipulation of 360o images and video of geologic phenomena and cultural heritage sites in Alaska, England, and France. Additionally, we will generate intentionally altered perspectives to lend a surrealistic quality to the landscapes. Locations include the Catacombs of Paris, the Palace of Versailles, and the Northern Lights over Fairbanks, Alaska. Some 360o view cameras now use small portable dual lens technology extending beyond the 180o fish eye lens previously used, providing better coverage and image quality. Virtual reality headsets range in level of sophistication and cost, with the most affordable versions using smart phones and Google Cardboard viewers. The equipment used in this presentation includes a Ricoh Theta S spherical imaging camera. Here we will demonstrate the use of 360o imaging with attendees being able to be part of the immersive environment and experience our locations as if they were visiting themselves.

  3. Toxicokinetics of bone lead.

    OpenAIRE

    Rabinowitz, M B

    1991-01-01

    This article discusses bone as a source of lead to the rest of the body and as a record of past lead exposure. Bone lead levels generally increase with age at rates dependent on the skeletal site and lead exposure. After occupational exposure, the slow decline in blood lead, a 5- to 19-year half-life, reflects the long skeletal half-life. Repeated measurements of bone lead demonstrate the slow elimination of lead from bone. Stable isotope ratios have revealed many details of skeletal uptake a...

  4. Leading change: a concept analysis.

    Science.gov (United States)

    Nelson-Brantley, Heather V; Ford, Debra J

    2017-04-01

    To report an analysis of the concept of leading change. Nurses have been called to lead change to advance the health of individuals, populations, and systems. Conceptual clarity about leading change in the context of nursing and healthcare systems provides an empirical direction for future research and theory development that can advance the science of leadership studies in nursing. Concept analysis. CINAHL, PubMed, PsycINFO, Psychology and Behavioral Sciences Collection, Health Business Elite and Business Source Premier databases were searched using the terms: leading change, transformation, reform, leadership and change. Literature published in English from 2001 - 2015 in the fields of nursing, medicine, organizational studies, business, education, psychology or sociology were included. Walker and Avant's method was used to identify descriptions, antecedents, consequences and empirical referents of the concept. Model, related and contrary cases were developed. Five defining attributes of leading change were identified: (a) individual and collective leadership; (b) operational support; (c) fostering relationships; (d) organizational learning; and (e) balance. Antecedents were external or internal driving forces and organizational readiness. The consequences of leading change included improved organizational performance and outcomes and new organizational culture and values. A theoretical definition and conceptual model of leading change were developed. Future studies that use and test the model may contribute to the refinement of a middle-range theory to advance nursing leadership research and education. From this, empirically derived interventions that prepare and enable nurses to lead change to advance health may be realized. © 2016 John Wiley & Sons Ltd.

  5. Lead Poisoning in Wild Birds

    Science.gov (United States)

    Lahner, Lesanna L.; Franson, J. Christian

    2009-01-01

    Lead in its various forms has been used for thousands of years, originally in cooking utensils and glazes and more recently in many industrial and commercial applications. However, lead is a potent, potentially deadly toxin that damages many organs in the body and can affect all animals, including humans. By the mid 1990s, lead had been removed from many products in the United States, such as paint and fuel, but it is still commonly used in ammunition for hunting upland game birds, small mammals, and large game animals, as well as in fishing tackle. Wild birds, such as mourning doves, bald eagles, California condors, and loons, can die from the ingestion of one lead shot, bullet fragment, or sinker. According to a recent study on loon mortality, nearly half of adult loons found sick or dead during the breeding season in New England were diagnosed with confirmed or suspected lead poisoning from ingestion of lead fishing weights. Recent regulations in some states have restricted the use of lead ammunition on certain upland game hunting areas, as well as lead fishing tackle in areas frequented by common loons and trumpeter swans. A variety of alternatives to lead are available for use in hunting, shooting sports, and fishing activities.

  6. Genetic alterations in head and neck squamous cell carcinomas

    Directory of Open Access Journals (Sweden)

    Nagai M.A.

    1999-01-01

    Full Text Available The genetic alterations observed in head and neck cancer are mainly due to oncogene activation (gain of function mutations and tumor suppressor gene inactivation (loss of function mutations, leading to deregulation of cell proliferation and death. These genetic alterations include gene amplification and overexpression of oncogenes such as myc, erbB-2, EGFR and cyclinD1 and mutations, deletions and hypermethylation leading to p16 and TP53 tumor suppressor gene inactivation. In addition, loss of heterozygosity in several chromosomal regions is frequently observed, suggesting that other tumor suppressor genes not yet identified could be involved in the tumorigenic process of head and neck cancers. The exact temporal sequence of the genetic alterations during head and neck squamous cell carcinoma (HNSCC development and progression has not yet been defined and their diagnostic or prognostic significance is controversial. Advances in the understanding of the molecular basis of head and neck cancer should help in the identification of new markers that could be used for the diagnosis, prognosis and treatment of the disease.

  7. Archives of Atmospheric Lead Pollution

    Science.gov (United States)

    Weiss, Dominik; Shotyk, William; Kempf, Oliver

    Environmental archives such as peat bogs, sediments, corals, trees, polar ice, plant material from herbarium collections, and human tissue material have greatly helped to assess both ancient and recent atmospheric lead deposition and its sources on a regional and global scale. In Europe detectable atmospheric lead pollution began as early as 6000years ago due to enhanced soil dust and agricultural activities, as studies of peat bogs reveal. Increased lead emissions during ancient Greek and Roman times have been recorded and identified in many long-term archives such as lake sediments in Sweden, ice cores in Greenland, and peat bogs in Spain, Switzerland, the United Kingdom, and the Netherlands. For the period since the Industrial Revolution, other archives such as corals, trees, and herbarium collections provide similar chronologies of atmospheric lead pollution, with periods of enhanced lead deposition occurring at the turn of the century and since 1950. The main sources have been industry, including coal burning, ferrous and nonferrous smelting, and open waste incineration until c.1950 and leaded gasoline use since 1950. The greatest lead emissions to the atmosphere all over Europe occurred between 1950 and 1980 due to traffic exhaust. A marked drop in atmospheric lead fluxes found in most archives since the 1980s has been attributed to the phasing out of leaded gasoline. The isotope ratios of lead in the various archives show qualitatively similar temporal changes, for example, the immediate response to the introduction and phasing out of leaded gasoline. Isotope studies largely confirm source assessments based on lead emission inventories and allow the contributions of various anthropogenic sources to be calculated.

  8. Toxicokinetics of bone lead.

    Science.gov (United States)

    Rabinowitz, M B

    1991-02-01

    This article discusses bone as a source of lead to the rest of the body and as a record of past lead exposure. Bone lead levels generally increase with age at rates dependent on the skeletal site and lead exposure. After occupational exposure, the slow decline in blood lead, a 5- to 19-year half-life, reflects the long skeletal half-life. Repeated measurements of bone lead demonstrate the slow elimination of lead from bone. Stable isotope ratios have revealed many details of skeletal uptake and subsequent release. The bulk turnover rates for compact bone are about 2% per year and 8% for spine. Turnover activity varies with age and health. Even though lead approximates calcium, radium, strontium, barium, fluorine, and other bone seekers, the rates for each are different. A simple, two-pool (bone and blood) kinetic model is presented with proposed numerical values for the changes in blood lead levels that occur with changes in turnover rates. Two approaches are offered to further quantify lead turnover. One involves a study of subjects with known past exposure. Changes in the ratio of blood lead to bone lead with time would reflect the course of bone lead availability. Also, stable isotopes and subjects who move from one geographical area to another offer opportunities. Sequential isotope measurements would indicate how much of the lead in blood is from current exposure or bone stores, distinct from changes in absorption or excretion.

  9. Lead in alcoholic beverages.

    Science.gov (United States)

    Sherlock, J C; Pickford, C J; White, G F

    1986-01-01

    Following the finding that blood lead concentrations in middle-aged men were positively associated with alcohol consumption, the Royal Commission on Environmental Pollution recommended that information on lead in alcoholic beverages be obtained. The results reported here were obtained in response to the Royal Commission's request. About 90% of canned and bottled beers contained less than or equal to 10 micrograms/l of lead, whereas nearly half the draught beers sampled contained greater than 10 micrograms/l and 4% contained greater than 100 micrograms/l. Opening the cans and bottles and pouring the contents into a glass had no significant effect on the lead concentration in the beer. All wines sampled directly from the bottle, that is without pouring, contained less than 250 micrograms/l of lead. However the lead concentration in some wines contained in lead-capped bottles increased significantly when the wine was poured from the bottle, in one instance the increment was 1890 micrograms/l. It is concluded that consumption of beer containing 50 micrograms/l of lead could make a substantial contribution to blood lead concentrations in man. Consumption of 1 l/day of wine containing 150 micrograms/l of lead could also make a major contribution to blood lead concentrations. Lead contamination of wine when it is poured from a bottle, which had been lead-capped, can sometimes greatly increase lead concentrations in the wine.

  10. 29 CFR 1910.1025 - Lead.

    Science.gov (United States)

    2010-07-01

    ... section. (7) Additional monitoring. Whenever there has been a production, process, control or personnel... production, process, or control which might result in a change in employee exposure to lead. (ii... occupations, including primary and secondary lead smelting, lead storage battery manufacturing, lead pigment...

  11. Lead inclusions in aluminium

    International Nuclear Information System (INIS)

    Johnson, E.; Johansen, A.; Sarholt-Kristensen, L.; Andersen, H.H.; Grabaek, L.; Bohr, J.

    1990-01-01

    Ion implantation at room temperature of lead into aluminum leads to spontaneous phase separation and formation of lead precipitates growing topotactically with the matrix. Unlike the highly pressurized (∼ 1-5 GPa) solid inclusions formed after noble gas implantations, the pressure in the lead precipitates is found to be less than 0.12 GPa. Recently the authors have observed the result that the lead inclusions in aluminum exhibit both superheating and supercooling. In this paper they review and elaborate on these results. Small implantation-induced lead precipitates embedded in an aluminum matrix were studied by x-ray diffraction

  12. Altering prolactin concentrations in sows.

    Science.gov (United States)

    Farmer, C

    2016-07-01

    Prolactin has a multiplicity of actions, but it is of particular importance in gestating and lactating animals. In sows, it is involved in the control of mammary development and also holds essential roles in the lactogenic and galactopoietic processes. Furthermore, low circulating concentrations of prolactin are associated with the agalactia syndrome. The crucial role of prolactin makes it important to understand the various factors that can alter its secretion. Regulation of prolactin secretion is largely under the negative control of dopamine, and dopamine agonists consistently decrease prolactin concentrations in sows. On the other hand, injections of dopamine antagonists can enhance circulating prolactin concentrations. Besides pharmacologic agents, many other factors can also alter prolactin concentrations in sows. The use of Chinese-derived breeds, for instance, leads to increased prolactin concentrations in lactating sows compared with standard European white breeds. Numerous husbandry and feeding practices also have a potential impact on prolactin concentrations in sows. Factors, such as provision of nest-building material prepartum, housing at farrowing, high ambient temperature, stress, transient weaning, exogenous thyrotropin-releasing factor, exogenous growth hormone-releasing factor, nursing frequency, prolonged photoperiod, fasting, increased protein and/or energy intake, altered energy sources, feeding high-fiber diets, sorghum ergot or plant extracts, were all studied with respect to their prolactinemic properties. Although some of these practices do indeed affect circulating prolactin concentrations, none leads to changes as drastic as those brought about by dopamine agonists or antagonists. It appears that the numerous factors regulating prolactin concentrations in sows are still not fully elucidated, and that studies to develop novel applicable ways of increasing prolactin concentrations in sows are warranted. Crown Copyright © 2015. Published

  13. VOLUMETRIC LEAD ASSAY

    International Nuclear Information System (INIS)

    Ebadian, M.A.; Dua, S.K.; Roelant, David; Kumar, Sachin

    2001-01-01

    This report describes a system for handling and radioassay of lead, consisting of a robot, a conveyor, and a gamma spectrometer. The report also presents a cost-benefit analysis of options: radioassay and recycling lead vs. disposal as waste

  14. Leading Causes of Blindness

    Science.gov (United States)

    ... Home Current Issue Past Issues Feature: Vision Leading Causes of Blindness Past Issues / Summer 2008 Table of ... million Americans have cataracts. They are the leading cause of blindness in the world. By age 80, ...

  15. NA49: lead-lead collision

    CERN Multimedia

    1996-01-01

    This is an image of an actual lead ion collision taken from tracking detectors on the NA49 experiment, part of the heavy ion project at CERN. These collisions produce a very complicated array of hadrons as the heavy ions break up. It is hoped that one of these collisions will eventually create a new state of matter known as quark-gluon plasma.

  16. Altered hypothalamic protein expression in a rat model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Wei-na Cong

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP, heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4, glycogen synthase1 (Gys1 and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1. In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.

  17. Pathogenic Mechanisms Involved in the Hematological Alterations of Arenavirus-induced Hemorrhagic Fevers

    Directory of Open Access Journals (Sweden)

    Roberto G. Pozner

    2013-01-01

    Full Text Available Viral hemorrhagic fevers (VHFs caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms.

  18. Radiation protection philosophy alters

    International Nuclear Information System (INIS)

    Firmin, G.

    1977-01-01

    Two significant events that have taken place this year in the field of radiation protection are reported. New SI units have been proposed (and effectively adopted), and the ICRP has revised its recommendations. Changes of emphasis in the latest recommendations (ICRP Publication 26) imply an altered radiation protection philosophy, in particular the relation of dose limits to estimates of average risk, an altered view of the critical organ approach and a new attitude to genetic dose to the population. (author)

  19. ALICE: Simulated lead-lead collision

    CERN Document Server

    2003-01-01

    This track is an example of simulated data modelled for the ALICE detector on the Large Hadron Collider (LHC) at CERN, which will begin taking data in 2008. ALICE will focus on the study of collisions between nuclei of lead, a heavy element that produces many different particles when collided. It is hoped that these collisions will produce a new state of matter known as the quark-gluon plasma, which existed billionths of a second after the Big Bang.

  20. Anti-cancer Lead Molecule

    KAUST Repository

    Sagar, Sunil

    2014-04-17

    Derivatives of plumbagin can be selectively cytotoxic to breast cancer cells. Derivative `A` (Acetyl Plumbagin) has emerged as a lead molecule for testing against estrogen positive breast cancer and has shown low hepatotoxicity as well as overall lower toxicity in nude mice model. The toxicity of derivative `A` was determined to be even lower than vehicle control (ALT and AST markers). The possible mechanism of action identified based on the microarray experiments and pathway mapping shows that derivative `A` could be acting by altering the cholesterol-related mechanisms. The low toxicity profile of derivative `A` highlights its possible role as future anti-cancer drug and/or as an adjuvant drug to reduce the toxicity of highly toxic chemotherapeutic drugs

  1. Lead Poison Detection

    Science.gov (United States)

    1976-01-01

    With NASA contracts, Whittaker Corporations Space Science division has developed an electro-optical instrument to mass screen for lead poisoning. Device is portable and detects protoporphyrin in whole blood. Free corpuscular porphyrins occur as an early effect of lead ingestion. Also detects lead in urine used to confirm blood tests. Test is inexpensive and can be applied by relatively unskilled personnel. Similar Whittaker fluorometry device called "drug screen" can measure morphine and quinine in urine much faster and cheaper than other methods.

  2. Glaucoma alters the circadian timing system.

    Directory of Open Access Journals (Sweden)

    Elise Drouyer

    Full Text Available Glaucoma is a widespread ocular disease and major cause of blindness characterized by progressive, irreversible damage of the optic nerve. Although the degenerative loss of retinal ganglion cells (RGC and visual deficits associated with glaucoma have been extensively studied, we hypothesize that glaucoma will also lead to alteration of the circadian timing system. Circadian and non-visual responses to light are mediated by a specialized subset of melanopsin expressing RGCs that provide photic input to mammalian endogenous clock in the suprachiasmatic nucleus (SCN. In order to explore the molecular, anatomical and functional consequences of glaucoma we used a rodent model of chronic ocular hypertension, a primary causal factor of the pathology. Quantitative analysis of retinal projections using sensitive anterograde tracing demonstrates a significant reduction (approximately 50-70% of RGC axon terminals in all visual and non-visual structures and notably in the SCN. The capacity of glaucomatous rats to entrain to light was challenged by exposure to successive shifts of the light dark (LD cycle associated with step-wise decreases in light intensity. Although glaucomatous rats are able to entrain their locomotor activity to the LD cycle at all light levels, they require more time to re-adjust to a shifted LD cycle and show significantly greater variability in activity onsets in comparison with normal rats. Quantitative PCR reveals the novel finding that melanopsin as well as rod and cone opsin mRNAs are significantly reduced in glaucomatous retinas. Our findings demonstrate that glaucoma impacts on all these aspects of the circadian timing system. In light of these results, the classical view of glaucoma as pathology unique to the visual system should be extended to include anatomical and functional alterations of the circadian timing system.

  3. Blood lead concentrations age.

    Science.gov (United States)

    Jusko, Todd A; Henderson, Charles R; Lanphear, Bruce P; Cory-Slechta, Deborah A; Parsons, Patrick J; Canfield, Richard L

    2008-02-01

    Few studies provide data directly relevant to the question of whether blood lead concentrations affect children's cognitive function. We examined the association between blood lead concentrations assessed throughout early childhood and children's IQ at 6 years of age. Children were followed from 6 months to 6 years of age, with determination of blood lead concentrations at 6, 12, 18, and 24 months, and 3, 4, 5, and 6 years of age. At 6 years of age, intelligence was assessed in 194 children using the Wechsler Preschool and Primary Scale of Intelligence-Revised. We used general linear and semiparametic models to estimate and test the association between blood lead concentration and IQ. After adjustment for maternal IQ, HOME scale scores, and other potential confounding factors, lifetime average blood lead concentration (mean = 7.2 microg/dL; median = 6.2 microg/dL) was inversely associated with Full-Scale IQ (p = 0.006) and Performance IQ scores (p = 0.002). Compared with children who had lifetime average blood lead concentrations IQ (91.3 vs. 86.4, p = 0.03). Nonlinear modeling of the peak blood lead concentration revealed an inverse association (p = 0.003) between peak blood lead levels and Full-Scale IQ down to 2.1 microg/dL, the lowest observed peak blood lead concentration in our study. Evidence from this cohort indicates that children's intellectual functioning at 6 years of age is impaired by blood lead concentrations well below 10 microg/dL, the Centers for Disease Control and Prevention definition of an elevated blood lead level.

  4. Music and Alterity Processes

    Directory of Open Access Journals (Sweden)

    Josep Martí

    2014-10-01

    Full Text Available The concept of alterity constitutes an important issue in anthropological research and, therefore, in the study of musical practices, as well. Without it, we could hardly understand other kinds of music situated in different spaces and time from the observer. In order to effectively approach these musical practices, we have to develop strategies to help us reduce as much as possible that which distorts the vision of the other. However, beyond the strictly epistemological and methodological issues, the study of music cannot ignore the ethical question related to the manner in which Western thought has understood and treated the other: through a hierarchical and stereotypical type of thinking based on the condition of otherness. Throughout the article, different alterity procedures are presented and discussed, such as synecdochization, exoticization, undervaluation, overvaluation, misunderstanding and exclusion. Taking these different alterity strategies into account may help us to better understand how the musical other is constructed, used and ultimately instrumentalized.

  5. Discontinuous Change: Leading Organizational Transformation.

    Science.gov (United States)

    Nadler, David A.; And Others

    This book provides insights into the dynamics of organizational transformation and presents a diagnostic framework for leading organizations through periods of radical change. Part 1 provides a framework for looking at the different types of change and the action strategies for dealing with them. Chapters include: (1) "Change Leadership: Core…

  6. EFFECT OF LEAD ACETATE

    African Journals Online (AJOL)

    MICROSOFT

    A significant (P<0.05) increase was recorded in GPT, creatinine and uric acid levels ... chemical composition of the compound containing lead, ... their body weight. Each group comprised five chicks. Treatment. Groups A, B, C, D, E and F were treated once a day with lead acetate at a dose rate of 80, 120, 160, 200, 240 and ...

  7. Leadership, Leaders, and Leading

    Science.gov (United States)

    Dean, Peter J.

    2004-01-01

    Arguably, the most important need in society today is to create individuals who will take action positively and progressively to lead in the private organization, in the the public institution, or in the governmental agency. Leadership action should not be held hostage by the notion that only those in formal positions of leadership can lead.…

  8. Thermal alteration of aquatic ecosystems

    International Nuclear Information System (INIS)

    Gibbons, J.W.; Sharitz, R.R.

    1974-01-01

    The studies summarized emphasize that heated effluents may function to enrich or to stress an ecosystem, depending upon the biological feature examined. However, the potential for negative impact on aquatic environments must not be underestimated. The ultimate consequences of the sometimes drastic alteration of behavior patterns and life-history phenomena in the surviving inhabitants of thermal areas have yet to be assessed. The relatively short time span of thermal field studies has not allowed thorough understanding of the biological chain reactions that may take place as physiological and genetic adjustments are made. Ensuing changes in species interactions, practically uninvestigated at this time, may create heretofore unsuspected ecosystem changes. Man's challenge for the future is to gain a more thorough comprehension of thermal ecology and to determine how waste heat may be used as an energy subsidy rather than a stress to aquatic systems. These and subsequent studies may assist in understanding how natural ecosystems respond to temperature elevation and will lead to the development of concepts and principles pertaining to thermally altered environmental systems. (U.S.)

  9. Genetic alterations and epigenetic changes in hepatocarcinogenesis

    Directory of Open Access Journals (Sweden)

    Luz Stella Hoyos Giraldo

    2007-02-01

    Full Text Available

    Hepatocarcinogenesis as hepatocellular carcinoma (HCC is associated with background of chronic liver disease usually in association with cirrhosis, marked hepatic fibrosis, hepatitis B virus (HBV and/or hepatitis virus (HCV infection, chronic inflammation, Aflatoxin B1(AFB1 exposure, chronic alcoholism, metabolic disorder of the liver and necroinflamatory liver disease. Hepatocarcinogenesis involve two mechanisms, genetic alterations (with changes in the cell's DNA sequence and epigenetic changes (without changes in the cell's DNA sequence, but changes in the pattern of gene expression that can persist through one or more generations (somatic sense. Hepatocarcinogenesis is associated with activation of oncogenes and decreased expression of tumor suppressor genes (TSG; include those involved in cell cycle control, apoptosis, DNA repair, immortalization and angiogenesis. AFB1 is metabolized in the liver into a potent carcinogen, aflatoxin 8, 9-epoxide, which is detoxified by epoxide hydrolase (EPHX and glutathione S-transferase M1 (GSTM1.

    A failure of detoxification processes can allow to mutagenic metabolite to bind to DNA and inducing P53 mutation. Genetic polymorphism of EPHX and GSTM1 can make individuals more susceptible to AFB1. Epigenetic inactivation of GSTP1 by promoter hypermethylation plays a role in the development of HCC because, it leads that electrophilic metabolite increase DNA damage and mutations. HBV DNA integration into the host chromosomal DNA of hepatocytes has been detected in HBV-related HCC.

    DNA tumor viruses cause cancer mainly by interfering with cell cycle controls, and activating the cell's replication machinery by blocking the action of key TSG. HBx protein is a

  10. Altered calcium metabolism: the probable major biochemical lesion ...

    African Journals Online (AJOL)

    These data are suggestive of altered calcium metabolism impairing cell membrane stabilization, the vasorelaxing effect of calcium and cell signaling. Altered calcium metabolism may be the major biochemical lesion underlying many pathological and clinical states of lead toxicity. Journal of Biomedical Investigation Vol.

  11. Recent advances in the understanding of sepsis-induced alterations in the neuroendocrine system.

    Science.gov (United States)

    Wahab, Fazal; Atika, Bibi; Oliveira-Pelegrin, Gabriela Ravanelli; Rocha, Maria José Alves

    2013-12-01

    Sepsis is a fatal systemic inflammatory disease. It is caused by an immune system inflammatory response to the entry of microorganisms or their products into the blood circulatory system. The pathophysiological mechanisms of sepsis are still poorly understood. The presence of microorganisms in the systemic circulation causes activation of the immune system, which in turn leads to a robust release of inflammatory cytokines. These inflammatory cytokines result in alterations across all important physiological systems, including the neuroendocrine system. Neuroendocrine responses differ between the acute and the late phase of sepsis. In the acute phase there are robust alterations in the secretion of neuroendocrine hormones in response to body demand. In the late phase, the plasma concentrations of some hormones remain low, despite heavy systemic demand, whereas several others increase despite of diminished needs. In this review, we give a brief overview on sepsis-induced major alterations in neuroendocrine secretions, and summarize current knowledge about mechanisms and targets for their treatment.

  12. Differential microstructural alterations in rat cerebral cortex in a model of chronic mild stress depression

    DEFF Research Database (Denmark)

    Khan, Ahmad Raza; Kroenke, Christopher D; Wiborg, Ove

    2018-01-01

    Chronic mild stress leads to depression in many cases and is linked to several debilitating diseases including mental disorders. Recently, neuronal tracing techniques, stereology, and immunohistochemistry have revealed persistent and significant microstructural alterations in the hippocampus......, hypothalamus, prefrontal cortex, and amygdala, which form an interconnected system known as the stress circuit. Most studies have focused only on this circuit, however, some studies indicate that manipulation of sensory and motor systems may impact genesis and therapy of mood disorders and therefore...... these areas should not be neglected in the study of brain microstructure alterations in response to stress and depression. For this reason, we explore the microstructural alterations in different cortical regions in a chronic mild stress model of depression. The study employs ex-vivo diffusion MRI (d...

  13. Lead levels - blood

    Science.gov (United States)

    Blood lead levels ... A blood sample is needed. Most of the time blood is drawn from a vein located on the inside ... may be used to puncture the skin. The blood collects in a small glass tube called a ...

  14. Lead User Innovation

    DEFF Research Database (Denmark)

    Brem, Alexander; Larsen, Henry

    2015-01-01

    User innovation and especially the integration of lead users is a key topic in the innovation management literature of recent years. This paper contributes by providing a rare perspective into what easily could be seen as innovation failure, shown from two perspectives. We show how a lack of shared...... imagination hampers participation and kills innovation between interdependent stakeholders at the threshold between invention and innovation in practice. We present a first case in the fun-sport industry where an external lead user and diverse firm representatives in different functions fail to create......, deliver and capture the value of an innovatively new device together. From the perspective of the lead user, we show antecedents and effects of social interaction between organizational actors and the lead user on the development of social capital, especially trust and shared imagination. The second case...

  15. Lead in Construction

    National Research Council Canada - National Science Library

    1993-01-01

    Although Occupational Safety and Health Administration (OSHA) regulations for occupational lead exposure have been in effect since 1971 for the construction and general industries, the agency regulations for general industry in 1978...

  16. Lead poisoning in dogs

    International Nuclear Information System (INIS)

    Zook, B.C.; Carpenter, J.L.; Leeds, E.B.

    1969-01-01

    Lead poisoning was diagnosed and studied in 60 dogs. It was found that lead poisoning is a common disease of young dogs, especially in the summer and fall, and is related to their chewing and eating habits resulting in the ingestion of paint, linoleum, or other lead-containing materials. The signs were characterized by gastrointestinal dysfunction (colic, vomiting, and diarrhea) and nervous disorders (convulsions, hysteria, nervousness, behavioral changes). The blood findings, which the authors consider nearly pathognomonic, consisted of numerous stippled and immature (especially nucleated) erythrocytes in the absence of severe anemia. Protein and casts were frequently found in the urine. Radiography sometimes revealed lead-containing particles in the gastro-intestinal tract, and lead lines were occasionally detected in the metaphysis of long bones in immature dogs. Treatment with calcium ethylenediamine-tetraacetic acid resulted in rapid and often dramatic recoveries in nearly all instances. Removal of lead from the gastrointestinal tract and treatment to relieve pronounced central nervous disorders was sometimes necessary. 40 references, 6 figures, 7 tables

  17. Drowning: a leading killer!

    Directory of Open Access Journals (Sweden)

    Nuno Domingos Garrido

    2016-10-01

    Full Text Available Drowning kills at least 372,000 people worldwide every year and is the 3rd leading cause of unintentional death, accounting for 7% of all deaths stemming from accidents (WHO, 2014. Conceptually, “drowning” is a complex and multi-faceted phenomenon, characterized as a chain of events (Bierens, 2006. Drowning is defined as the process of experiencing respiratory impairment from immersion or submersion in liquid. Research on drowning as a phenomenon presents several difficulties - most of all, that global data concerning the number of occurrences are not accurate. Nevertheless, detailed analysis of the registered incidents allows the identification of risk factors of drowning. An in-depth analysis of the risk factors is the basis for the creation of targeted and effective strategies to prevent drowning. Due to variability of situations which could lead to a drowning episode, experts suggest the adoption of a multi-layer prevention model, rather than opting for isolated measures, since no single measure can prevent all deaths and injuries caused by submersion. Among the preventive measures we would like to emphasize instruction in swimming and water safety. So, what does "knowing how to swim" really mean? Some authors define mastery of this competence as swimming a given distance, while others put the emphasis on how this/any given distance is swum (Stallman, Junge, & Blixt, 2008. It has long been realized that there is no contradiction between learning those competencies which make a person less susceptible to drowning and those competencies which prepare the path towards higher levels of performance and competition. Aquatic movement researchers and practitioners and drowning prevention researchers and practitioners, share in the responsibility for drowning prevention though they are often unaware of it. The question “What should be taught to children?” is too infrequently asked. There remains great variation in what is taught and programs

  18. Mortar alteration: experimental study and ancient analogues

    International Nuclear Information System (INIS)

    Rassineux, Francois

    1987-01-01

    As the durability of cemented matrices is a matter of great importance in numerous domains, notably for the long term reliability of surface storages of radioactive wastes, the objective of this research thesis is to define mechanisms of evolution of cemented matrices when in contact with diluted aqueous solutions. The author notably studied the influence of the lixiviation mode on the evolution of two mortars having different compositions (pH, CO 2 pressure, system containment, and cement mineralogical nature appear to be the main governing parameters), the alteration (dissolution is the prevailing process in the interaction between cemented matrices and a diluted solution such as rain water), and ancient binders (archaeological binders containing mineral phases such as hydrated calcium silicates or hydro-grossulars). The obtained results lead to the definition of alteration mechanisms in modern cements, and highlight factors governing the durability of these materials when submitted to meteoric alteration [fr

  19. Magnesium Diboride Current Leads

    Science.gov (United States)

    Panek, John

    2010-01-01

    A recently discovered superconductor, magnesium diboride (MgB2), can be used to fabricate conducting leads used in cryogenic applications. Dis covered to be superconducting in 2001, MgB2 has the advantage of remaining superconducting at higher temperatures than the previously used material, NbTi. The purpose of these leads is to provide 2 A of electricity to motors located in a 1.3 K environment. The providing environment is a relatively warm 17 K. Requirements for these leads are to survive temperature fluctuations in the 5 K and 11 K heat sinks, and not conduct excessive heat into the 1.3 K environment. Test data showed that each lead in the assembly could conduct 5 A at 4 K, which, when scaled to 17 K, still provided more than the required 2 A. The lead assembly consists of 12 steelclad MgB2 wires, a tensioned Kevlar support, a thermal heat sink interface at 4 K, and base plates. The wires are soldered to heavy copper leads at the 17 K end, and to thin copper-clad NbTi leads at the 1.3 K end. The leads were designed, fabricated, and tested at the Forschungszentrum Karlsruhe - Institut foer Technische Physik before inclusion in Goddard's XRS (X-Ray Spectrometer) instrument onboard the Astro-E2 spacecraft. A key factor is that MgB2 remains superconducting up to 30 K, which means that it does not introduce joule heating as a resistive wire would. Because the required temperature ranges are 1.3-17 K, this provides a large margin of safety. Previous designs lost superconductivity at around 8 K. The disadvantage to MgB2 is that it is a brittle ceramic, and making thin wires from it is challenging. The solution was to encase the leads in thin steel tubes for strength. Previous designs were so brittle as to risk instrument survival. MgB2 leads can be used in any cryogenic application where small currents need to be conducted at below 30 K. Because previous designs would superconduct only at up to 8 K, this new design would be ideal for the 8-30 K range.

  20. Association between blood lead and the risk of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Fang, Fang; Kwee, Lydia C; Allen, Kelli D; Umbach, David M; Ye, Weimin; Watson, Mary; Keller, Jean; Oddone, Eugene Z; Sandler, Dale P; Schmidt, Silke; Kamel, Freya

    2010-05-15

    The authors conducted a 2003-2007 case-control study including 184 cases and 194 controls to examine the association between blood lead and the risk of amyotrophic lateral sclerosis (ALS) among US veterans and to explore the influence on this association of bone turnover and genetic factors related to lead toxicokinetics. Blood lead, plasma biomarkers of bone formation (procollagen type 1 amino-terminal peptide (PINP)) and resorption (C-terminal telopeptides of type 1 collagen (CTX)), and the K59N polymorphism in the delta-aminolevulinic acid dehydratase gene, ALAD, were measured. Odds ratios and 95% confidence intervals for the association of blood lead with ALS were estimated with unconditional logistic regression after adjustment for age and bone turnover. Blood lead levels were higher among cases compared with controls (P lead was associated with a 1.9-fold increased risk of ALS (95% confidence interval: 1.3, 2.7) after adjustment for age and CTX. Additional adjustment for PINP did not alter the results. Significant lead-ALS associations were observed in substrata of PINP and CTX levels. The K59N polymorphism in the ALAD gene did not modify the lead-ALS association (P = 0.32). These results extend earlier findings by accounting for bone turnover in confirming the association between elevated blood lead level and higher risk of ALS.

  1. A lead isotope distribution study in swine tissue using ICP-MS

    Science.gov (United States)

    May, T.W.; Wiedmeyer, Ray H.; Brown, L.D.; Casteel, S.W.

    1999-01-01

    In the United States lead is an ubiquitous environmental pollutant that is a serious human health hazard, especially for women of childbearing age, developing fetuses, and young children. Information concerning the uptake and distribution of lead to maternal and fetal tissues during pregnancy is poorly documented. A study was designed using domestic swine and lead isotope enrichment methodology to focus on maternal absorption and distribution of lead into bone and soft tissues, including the fetal compartment, under varying conditions of oral lead exposure and during altered physiological states (pregnant vs unbred). Total lead levels and Pb207/Pb206 ratios in bone (femur and vertebra), blood, and soft tissues (liver, kidney, brain) were determined by ICP-MS. Lead in fetal tissues derived from maternal bone could be differentiated from that derived from exogenous dosing. Unbred swine absorbed much less lead than pregnant females receiving the same dose. The accuracy and precision of ICP-MS at the instrumental level and for the entire method (sample collection, digestion, and analysis) were evaluated for both Pb207/Pb206 ratios and total lead. Several changes were suggested in method design to improve both instrumental and total method precision.

  2. Association Between Blood Lead and the Risk of Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Fang, Fang; Kwee, Lydia C.; Allen, Kelli D.; Umbach, David M.; Ye, Weimin; Watson, Mary; Keller, Jean; Oddone, Eugene Z.; Sandler, Dale P.; Schmidt, Silke; Kamel, Freya

    2010-01-01

    The authors conducted a 2003–2007 case-control study including 184 cases and 194 controls to examine the association between blood lead and the risk of amyotrophic lateral sclerosis (ALS) among US veterans and to explore the influence on this association of bone turnover and genetic factors related to lead toxicokinetics. Blood lead, plasma biomarkers of bone formation (procollagen type 1 amino-terminal peptide (PINP)) and resorption (C-terminal telopeptides of type 1 collagen (CTX)), and the K59N polymorphism in the δ-aminolevulinic acid dehydratase gene, ALAD, were measured. Odds ratios and 95% confidence intervals for the association of blood lead with ALS were estimated with unconditional logistic regression after adjustment for age and bone turnover. Blood lead levels were higher among cases compared with controls (P < 0.0001, age adjusted). A doubling of blood lead was associated with a 1.9-fold increased risk of ALS (95% confidence interval: 1.3, 2.7) after adjustment for age and CTX. Additional adjustment for PINP did not alter the results. Significant lead-ALS associations were observed in substrata of PINP and CTX levels. The K59N polymorphism in the ALAD gene did not modify the lead-ALS association (P = 0.32). These results extend earlier findings by accounting for bone turnover in confirming the association between elevated blood lead level and higher risk of ALS. PMID:20406759

  3. Gas cooled leads

    International Nuclear Information System (INIS)

    Shutt, R.P.; Rehak, M.L.; Hornik, K.E.

    1993-01-01

    The intent of this paper is to cover as completely as possible and in sufficient detail the topics relevant to lead design. The first part identifies the problems associated with lead design, states the mathematical formulation, and shows the results of numerical and analytical solutions. The second part presents the results of a parametric study whose object is to determine the best choice for cooling method, material, and geometry. These findings axe applied in a third part to the design of high-current leads whose end temperatures are determined from the surrounding equipment. It is found that cooling method or improved heat transfer are not critical once good heat exchange is established. The range 5 5 but extends over a large of values. Mass flow needed to prevent thermal runaway varies linearly with current above a given threshold. Below that value, the mass flow is constant with current. Transient analysis shows no evidence of hysteresis. If cooling is interrupted, the mass flow needed to restore the lead to its initially cooled state grows exponentially with the time that the lead was left without cooling

  4. Prevention of lead toxicity in US children.

    Science.gov (United States)

    Lanphear, Bruce P; Dietrich, Kim N; Berger, Omer

    2003-01-01

    During the past 2 decades, the proportion of US children who have blood lead concentrations of 10 microg/dL or higher declined by over 80% after the elimination of leaded gasoline and lead solder from canned foods, and a ban on leaded paint used in housing and other consumer products. Fatalities and symptomatic lead poisoning are now rare. Residential lead hazards, which are exceedingly difficult to control, are currently the major source of lead intake for children. Undue lead exposure has retreated into 2 major risk groups; impoverished children who live in older, poorly maintained rental housing and more affluent children who live in older housing undergoing renovation. Despite the dramatic decline in children's blood lead levels, lead toxicity remains epidemic among impoverished children who live in older rental housing, especially those who live in the northeastern and midwestern regions of the United States. There are increasing data linking lead exposure with other systemic effects including delinquency, dental caries, and learning problems. Moreover, there is evidence indicating that there is no discernible threshold for lead-associated cognitive deficits. Thus, it is increasingly important to shift our efforts toward the primary prevention of childhood lead exposure from residential hazards. This article reviews the epidemiology and control of childhood lead exposure, focusing especially on steps necessary to shift toward primary prevention.

  5. Leading healthcare in complexity.

    Science.gov (United States)

    Cohn, Jeffrey

    2014-12-01

    Healthcare institutions and providers are in complexity. Networks of interconnections from relationships and technology create conditions in which interdependencies and non-linear dynamics lead to surprising, unpredictable outcomes. Previous effective approaches to leadership, focusing on top-down bureaucratic methods, are no longer effective. Leading in complexity requires leaders to accept the complexity, create an adaptive space in which innovation and creativity can flourish and then integrate the successful practices that emerge into the formal organizational structure. Several methods for doing adaptive space work will be discussed. Readers will be able to contrast traditional leadership approaches with leading in complexity. They will learn new behaviours that are required of complexity leaders, along with challenges they will face, often from other leaders within the organization.

  6. Protective role of flaxseed oil against lead acetate induced oxidative ...

    African Journals Online (AJOL)

    Even though the toxic effects of lead compounds had been studied over many years, inconsistent results have been obtained about their oxidative stress in the testes of adult rats. Lead acetate (20 mg/kg) alters the histology of testes as well as enhances lipid peroxidation and nitric oxide production in both serum and testes ...

  7. From the Cause of the Other to Minoritarian Strategy: The Politics and Clinic of Included Alterity

    Directory of Open Access Journals (Sweden)

    Guillaume Sibertin-Blanc

    2015-01-01

    Full Text Available This article examines certain problems related to the “antinomical” distinction, proposed by Étienne Balibar, between a majority strategy and a minority strategy. Orientated by the deleuzo-guattarian theory of “becoming-minor”, and confronting it with three different political scenes taken from Frantz Fanon, Jacques Rancière and Judith Butler, we seek to distinguish different manners of thinking the inclusion of a “cause of the other”, or of a minority point of view, in the construction of emancipatory political identities. These are different ways of problematizing a minority strategy by relating it to practices of disidentification as the very content of political subjectivation. But the hypothesis that will crystalize in the course of this confrontation is that of an internal antinomy in the idea of minority strategy itself, that intensifies when the dominant identities loose the assurance of their own “majority”, or when the difference between the majoritarian and the minoritarian becomes tendencially unassignable at the same time as it becomes more difficult to differentiate the violence of the exclusion of minorities to the violence of their inclusion.

  8. Methyl jasmonate deficiency alters cellular metabolome including the aminome of tomato (Solanum lycopersicum L.) fruit

    Science.gov (United States)

    Lipoxygenase (LOX) catalyzes oxidation of C-13 atom of C:18 polyunsaturated fatty acids and produces jasmonic acid and other oxylipins that have important biological relevance. However, the role of these important molecules in cellular metabolism is barely understood. We have used a transgenic appro...

  9. ETS-Associated Genomic Alterations including ETS2 Loss Markedly Affect Prostate Cancer Progression

    Science.gov (United States)

    2015-10-01

    Approximately half of all prostate cancers contain a fusion between two genes, TMPRSS2 and ERG , and a further half of these contain a deletion of...the 14 genes lying between TMPRSS2 and ERG . I have now performed a screen involving inhibition of each of these 14 genes, and am currently...validating whether one or more of these genes does indeed affect cellular proliferation in vitro and in vivo. 15. SUBJECT TERMS prostate cancer, TMPRSS2- ERG

  10. Lead toxicity in plants

    OpenAIRE

    Sharma, Pallavi; Dubey, Rama Shanker

    2005-01-01

    Contamination of soils by heavy metals is of widespread occurrence as a result of human, agricultural and industrial activities. Among heavy metals, lead is a potential pollutant that readily accumulates in soils and sediments. Although lead is not an essential element for plants, it gets easily absorbed and accumulated in different plant parts. Uptake of Pb in plants is regulated by pH, particle size and cation exchange capacity of the soils as well as by root exudation and other physico-che...

  11. Effects of sublethal exposure to lead on levels of energetic compounds in Procambarus clarkii (Girard, 1852)

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, M.; Torreblanca, A.; Del Ramo, J.; Diaz-Mayans, J. (Univ. of Valencia (Spain))

    1994-05-01

    Lead is neither essential nor beneficial to living organisms; all existing data show that its metabolic effects are adverse. Lead is toxic to all phyla of aquatic biota. Most of the lead discharged into surface water is rapidly incorporated into suspended and bottom sediments. The American red crayfish, Procambarus clarkii, lives in a wide range of environmental conditions that include highly polluted waters. Lead present in take sediments can be available to aquatic animals such as P. clarkii because it is a detritivor and burrow into the sediment. In fact, we found remarkable levels of lead in tissues of P. clarkii caught in Albufera Lake and kept 15 days in clean water (e. g. 223 [mu]g/g dry weight in gills). Furthermore, P. clarkii has a high capacity for lead accumulation from water, and gills were the most important tissue of lead accumulation. Among effects that contaminants have on the physiology of the organisms, energetic state variables are important, since they will alter both survival and reproduction. Hepatopancreas is a major site for the energetic reserve in crayfish and is a site of lead accumulation, although metal concentration in this organ is not as high as gills. The purpose of this study was to examine changes in energy reserves in hepatopancreas and gills of the crayfish P. clarkii, in response to sublethal exposure to lead. Gills are directly exposed to contaminants in the environment, and they are the first organ showing alterations by the action of the contaminants. Hepatopancreas was also chosen due to both, its relevance in the energetic metabolism and its role in heavy metal detoxification mechanisms.

  12. The lead and lead-acid battery industries during 2002 and 2007 in China

    Science.gov (United States)

    Chen, H. Y.; Li, A. J.; Finlow, D. E.

    In the past 15 years, the center of the international lead market has shifted to China. China has become the largest producer of raw and refined lead, plus the largest consumer. This paper reviews the status of the lead and lead-acid battery industries in China, including lead mining, lead refining, secondary lead production, the lead-acid battery industry, new opportunities for lead-acid batteries, and the environmental problems associated with lead and lead-acid batteries. The output of raw and refined lead has increased annually in China, and now accounts for more than 30% of the world total. As a result of a change in the Chinese government's policy regarding the export of lead, plus an increase in the price of lead, the profits of Chinese lead manufacturers were significantly reduced, the trade deficit of the Chinese lead industry increased, the operating rates of lead smelter enterprises greatly reduced, and some small enterprises were forced to shut down. At the present time, an increasing number of enterprises have begun to produce secondary lead, and the scale of production has expanded from tens of tons to tens of thousands of tons. In 2006, the output of secondary lead in China reached 700,000 tons, but outdated technology and equipment limited development of the secondary lead industry. Because of serious pollution problems, raw material shortages, and fierce price competition in the battery market, changes in the development of the lead-acid battery industry have been dramatic; approximately one thousand medium-sized and small lead-acid battery producers have been closed in the past 3 years. The output of large lead-acid battery enterprises has not been reduced, however, as a result of their manufacturing technology and equipment being comparable to those in other advanced industrial countries. In China, the flourishing development of electric bicycles, electric tricycles, and photovoltaic energy systems should provide ongoing opportunities for the

  13. Girls Leading Outward

    Science.gov (United States)

    Hamed, Heather; Reyes, Jazmin; Moceri, Dominic C.; Morana, Laura; Elias, Maurice J.

    2011-01-01

    The authors describe a program implemented in Red Bank Middle School in New Jersey to help at-risk, minority middle school girls realize their leadership potential. The GLO (Girls Leading Outward) program was developed by the Developing Safe and Civil Schools Project at Rutgers University and is facilitated by university students. Selected middle…

  14. Turning lead into gold

    DEFF Research Database (Denmark)

    Jensen, Steffen Moltrup Ernø

    For years the field of entrepreneurship has been blinded by the alchemical promise of turning lead into gold, of finding the ones most likely to become the next Branson, Zuckerberg or Gates. The promise has been created in the midst of political and scientific agendas where certain individuals...

  15. Relational Perspectives on Leading

    DEFF Research Database (Denmark)

    Relational Perspectives on Leading discusses leadership from a relational and social constructionism perspective as practiced on an everyday basis between people. The book pursues a fast growing, practice-based approach - particularly within the Anglo-Saxon parts of the world - to organization...

  16. Scientometry Leading us Astray

    Czech Academy of Sciences Publication Activity Database

    Haindl, Michal

    2010-01-01

    Roč. 2010, č. 82 (2010), s. 8-8 ISSN 0926-4981 Institutional research plan: CEZ:AV0Z10750506 Keywords : scientometry Subject RIV: BD - Theory of Information http://ercim-news.ercim.eu/en82/european-scene/ scientometry -leading-us-astray

  17. Lead exposure from aluminum cookware in Cameroon

    Energy Technology Data Exchange (ETDEWEB)

    Weidenhamer, Jeffrey D.; Kobunski, Peter A. [Department of Chemistry, Geology and Physics, 401 College Ave., Ashland University, Ashland, OH 44805 (United States); Kuepouo, Gilbert [Research and Education Centre for Development (CREPD), Yaounde (Cameroon); Corbin, Rebecca W. [Department of Chemistry, Geology and Physics, 401 College Ave., Ashland University, Ashland, OH 44805 (United States); Gottesfeld, Perry, E-mail: pgottesfeld@okinternational.org [Occupational Knowledge International, San Francisco, CA (United States)

    2014-10-15

    Blood lead levels have decreased following the removal of lead from gasoline in most of the world. However, numerous recent studies provide evidence that elevated blood lead levels persist in many low and middle-income countries around the world at much higher prevalence than in the more developed countries. One potential source of lead exposure that has not been widely investigated is the leaching of lead from artisanal aluminum cookware, which is commonly used in the developing world. Twenty-nine samples of aluminum cookware and utensils manufactured by local artisans in Cameroon were collected and analyzed for their potential to release lead during cooking. Source materials for this cookware included scrap metal such as engine parts, radiators, cans, and construction materials. The lead content of this cookware is relatively low (< 1000 ppm by X-ray fluorescence), however significant amounts of lead, as well as aluminum and cadmium were released from many of the samples using dilute acetic acid extractions at boiling and ambient temperatures. Potential exposures to lead per serving were estimated to be as high as 260 μg, indicating that such cookware can pose a serious health hazard. We conclude that lead, aluminum and cadmium can migrate from this aluminum cookware during cooking and enter food at levels exceeding recommended public health guidelines. Our results support the need to regulate lead content of materials used to manufacture these pots. Artisanal aluminum cookware may be a major contributor to lead poisoning throughout the developing world. Testing of aluminum cookware in other developing countries is warranted. - Highlights: • Cookware is manufactured in Cameroon from scrap aluminum including car parts. • Twenty-nine cookware samples were evaluated for their potential to leach lead. • Boiling extractions to simulate the effects of cooking released significant lead. • Potential lead exposures per serving are estimated as high as 260 μg.

  18. Lead exposure from aluminum cookware in Cameroon

    International Nuclear Information System (INIS)

    Weidenhamer, Jeffrey D.; Kobunski, Peter A.; Kuepouo, Gilbert; Corbin, Rebecca W.; Gottesfeld, Perry

    2014-01-01

    Blood lead levels have decreased following the removal of lead from gasoline in most of the world. However, numerous recent studies provide evidence that elevated blood lead levels persist in many low and middle-income countries around the world at much higher prevalence than in the more developed countries. One potential source of lead exposure that has not been widely investigated is the leaching of lead from artisanal aluminum cookware, which is commonly used in the developing world. Twenty-nine samples of aluminum cookware and utensils manufactured by local artisans in Cameroon were collected and analyzed for their potential to release lead during cooking. Source materials for this cookware included scrap metal such as engine parts, radiators, cans, and construction materials. The lead content of this cookware is relatively low (< 1000 ppm by X-ray fluorescence), however significant amounts of lead, as well as aluminum and cadmium were released from many of the samples using dilute acetic acid extractions at boiling and ambient temperatures. Potential exposures to lead per serving were estimated to be as high as 260 μg, indicating that such cookware can pose a serious health hazard. We conclude that lead, aluminum and cadmium can migrate from this aluminum cookware during cooking and enter food at levels exceeding recommended public health guidelines. Our results support the need to regulate lead content of materials used to manufacture these pots. Artisanal aluminum cookware may be a major contributor to lead poisoning throughout the developing world. Testing of aluminum cookware in other developing countries is warranted. - Highlights: • Cookware is manufactured in Cameroon from scrap aluminum including car parts. • Twenty-nine cookware samples were evaluated for their potential to leach lead. • Boiling extractions to simulate the effects of cooking released significant lead. • Potential lead exposures per serving are estimated as high as 260 μg.

  19. Altered metabolism in cancer

    Directory of Open Access Journals (Sweden)

    Locasale Jason W

    2010-06-01

    Full Text Available Abstract Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/

  20. (including travel dates) Proposed itinerary

    Indian Academy of Sciences (India)

    Ashok

    31 July to 22 August 2012 (including travel dates). Proposed itinerary: Arrival in Bangalore on 1 August. 1-5 August: Bangalore, Karnataka. Suggested institutions: Indian Institute of Science, Bangalore. St Johns Medical College & Hospital, Bangalore. Jawaharlal Nehru Centre, Bangalore. 6-8 August: Chennai, TN.

  1. Acid Sulfate Alteration on Mars

    Science.gov (United States)

    Ming, D. W.; Morris, R. V.

    2016-01-01

    A variety of mineralogical and geochemical indicators for aqueous alteration on Mars have been identified by a combination of surface and orbital robotic missions, telescopic observations, characterization of Martian meteorites, and laboratory and terrestrial analog studies. Acid sulfate alteration has been identified at all three landing sites visited by NASA rover missions (Spirit, Opportunity, and Curiosity). Spirit landed in Gusev crater in 2004 and discovered Fe-sulfates and materials that have been extensively leached by acid sulfate solutions. Opportunity landing on the plains of Meridiani Planum also in 2004 where the rover encountered large abundances of jarosite and hematite in sedimentary rocks. Curiosity landed in Gale crater in 2012 and has characterized fluvial, deltaic, and lacustrine sediments. Jarosite and hematite were discovered in some of the lacustrine sediments. The high elemental abundance of sulfur in surface materials is obvious evidence that sulfate has played a major role in aqueous processes at all landing sites on Mars. The sulfate-rich outcrop at Meridiani Planum has an SO3 content of up to 25 wt.%. The interiors of rocks and outcrops on the Columbia Hills within Gusev crater have up to 8 wt.% SO3. Soils at both sites generally have between 5 to 14 wt.% SO3, and several soils in Gusev crater contain around 30 wt.% SO3. After normalization of major element compositions to a SO3-free basis, the bulk compositions of these materials are basaltic, with a few exceptions in Gusev crater and in lacustrine mudstones in Gale crater. These observations suggest that materials encountered by the rovers were derived from basaltic precursors by acid sulfate alteration under nearly isochemical conditions (i.e., minimal leaching). There are several cases, however, where acid sulfate alteration minerals (jarosite and hematite) formed in open hydrologic systems, e.g., in Gale crater lacustrine mudstones. Several hypotheses have been suggested for the

  2. Circadian disorganization alters intestinal microbiota.

    Science.gov (United States)

    Voigt, Robin M; Forsyth, Christopher B; Green, Stefan J; Mutlu, Ece; Engen, Phillip; Vitaterna, Martha H; Turek, Fred W; Keshavarzian, Ali

    2014-01-01

    Intestinal dysbiosis and circadian rhythm disruption are associated with similar diseases including obesity, metabolic syndrome, and inflammatory bowel disease. Despite the overlap, the potential relationship between circadian disorganization and dysbiosis is unknown; thus, in the present study, a model of chronic circadian disruption was used to determine the impact on the intestinal microbiome. Male C57BL/6J mice underwent once weekly phase reversals of the light:dark cycle (i.e., circadian rhythm disrupted mice) to determine the impact of circadian rhythm disruption on the intestinal microbiome and were fed either standard chow or a high-fat, high-sugar diet to determine how diet influences circadian disruption-induced effects on the microbiome. Weekly phase reversals of the light:dark (LD) cycle did not alter the microbiome in mice fed standard chow; however, mice fed a high-fat, high-sugar diet in conjunction with phase shifts in the light:dark cycle had significantly altered microbiota. While it is yet to be established if some of the adverse effects associated with circadian disorganization in humans (e.g., shift workers, travelers moving across time zones, and in individuals with social jet lag) are mediated by dysbiosis, the current study demonstrates that circadian disorganization can impact the intestinal microbiota which may have implications for inflammatory diseases.

  3. LEAD SEVERING CONTRIVANCE

    Science.gov (United States)

    Widmaier, W.

    1958-04-01

    A means for breaking an electrical circuit within an electronic tube during the process of manufacture is described. Frequently such circuits must be employed for gettering or vapor coating purposes, however, since an external pair of corector pins having no use after manufacture, is undesirable, this invention permits the use of existing leads to form a temporary circuit during manufacture, and severing it thereafter. One portion of the temporary circuit, made from a springy material such as tungsten, is spot welded to a fusable member. To cut the circuit an external radiant heat source melts the fusable member, allowing the tensed tungsten spring to contract and break the circuit. This inexpensive arrangement is particularly useful when the tube has a great many external leads crowded into the tube base.

  4. CMS lead tungstate crystals

    CERN Multimedia

    Laurent Guiraud

    2000-01-01

    These crystals are made from lead tungstate, a crystal that is as clear as glass yet with nearly four times the density. They have been produced in Russia to be used as scintillators in the electromagnetic calorimeter on the CMS experiment, part of the LHC project at CERN. When an electron, positron or photon passes through the calorimeter it will cause a cascade of particles that will then be absorbed by these scintillating crystals, allowing the particle's energy to be measured.

  5. Bronchopulmonary Dysplasia Early Changes Leading To Long Term Consequences

    Directory of Open Access Journals (Sweden)

    Anne eHilgendorff

    2015-02-01

    Full Text Available Neonatal Chronic Lung Disease, i.e. Bronchopulmonary Dysplasia (BPD is characterized by impaired pulmonary development. Triggered by different risk factors including infections, hyperoxia and mechanical ventilation of the immature lung, remodeling of the extracellular matrix, apoptosis as well as altered growth factor signaling characterize the disease. The immediate consequences have been studied in different animal models supported by in vitro approaches leading to the successful application of these findings to the clinical setting in the past. Nonetheless, existing information about long-term consequences of the identified early and most likely sustained changes to the developing lung is limited. Interesting results point towards a tremendous impact on the pulmonary repair capacity as well as aging related processes in the adult lung.

  6. Aluminium and lead: molecular mechanisms of brain toxicity.

    Science.gov (United States)

    Verstraeten, Sandra V; Aimo, Lucila; Oteiza, Patricia I

    2008-11-01

    The fact that aluminium (Al) and lead (Pb) are both toxic metals to living organisms, including human beings, was discovered a long time ago. Even when Al and Pb can reach and accumulate in almost every organ in the human body, the central nervous system is a particular target of the deleterious effects of both metals. Select human population can be at risk of Al neurotoxicity, and Al is proposed to be involved in the etiology of neurodegenerative diseases. Pb is a widespread environmental hazard, and the neurotoxic effects of Pb are a major public health concern. In spite of the numerous efforts and the accumulating evidence in this area of research, the mechanisms of Al and Pb neurotoxicity are still not completely elucidated. This review will particularly address the involvement of oxidative stress, membrane biophysics alterations, deregulation of cell signaling, and the impairment of neurotransmission as key aspects involved Al and Pb neurotoxicity.

  7. Malignant lymphomas (including myeloproliferative disorders)

    International Nuclear Information System (INIS)

    Todd, I.D.H.

    1985-01-01

    This chapter deals with the radiotherapy and cytotoxic chemotherapy of the malignant lymphomas. Included within this group are Hodgkin's disease, non-Hodgkin's lymphoma, mycosis fungoides, and chronic lymphatic leukaemia. A further section deals with the myeloproliferative disorders, including granulocytic leukaemia, polycythaemia vera, and primary thrombocythaemia. Excluded are myeloma and reticulum cell sarcoma of bone and acute leukaemia. With regard to Hodgkin's disease, the past 25 years have seen general recognition of the curative potential of radiotherapy, at least in the local stages, and, more recently, awareness of the ability to achieve long-term survival after combination chemotherapy in generalised or in recurrent disease. At the same time the importance of staging has become appreciated and the introduction of procedures such as lymphography, staging laparotomy, and computer tomography (CT) has enormously increased its reliability. Advances have not been so dramatic in the complex group of non-Hodgkins's lymphomas, but are still very real

  8. Protect Your Family from Lead in Your Home

    Science.gov (United States)

    ... lead- based paint hazards before selling a house. • Real estate sales contracts must include a specific warning statement ... pamphlet, The Lead-Safe Certified Guide to Renovate Right, to learn about the lead-safe work practices ...

  9. Lead removal via soil washing and leaching

    Science.gov (United States)

    Lin, H. K.; Man, X. D.; Walsh, D. E.

    2001-12-01

    A soil washing and leaching process was tested for removing lead from soils. A soil-washing circuit, including size and gravity separations, was employed to remove the coarse metallic lead particles, while the leaching was applied to remove fine metallic lead particles and other lead species. The soil-washing tests proved that the metallic lead particles larger than 0.15 mm (100 mesh) could be effectively removed. The sodium-chloride-based leaching solution with ferric chloride or sodium hypochlorite as oxidants was adopted in the leaching. The leaching experimental results indicated that under the pH of 2 and Eh of 1,300 mV, the metallic lead particles smaller than 0.15 mm and other lead species can be dissolved in the leaching solution within 60 minutes.

  10. Tityus fasciolatus envenomation induced cardio-respiratory alterations in rats.

    Science.gov (United States)

    Pinto, M C L; Borboleta, L R; Melo, M B; Labarrére, C R; Melo, M M

    2010-06-01

    The present study characterized envenomation in young rats by Tityus fasciolatus, an endemic scorpion to Central Brazilian and state of Minas Gerais. Electrocardiographic examinations were performed prior to treatment and every 5 min during the first 30 min after envenomation. The cardiac blood profile [creatine kinase, CK isoenzyme MB, lactate dehydrogenase, aspartate aminotransferase and troponina] together with macroscopic and microscopic alterations in the lungs and heart were evaluated. Envenomated animals showed ECG changes suggesting electrolytic imbalance, myocarditis and venom interference on the conduction tissue. Biochemical analyses indicated myocardial damage with high levels of CK, CK-MB and LDH. Macroscopic and microscopic findings included detection of pulmonary haemorrhages. In conclusion, T. fasciolatus venom leads to acute cardio-respiratory changes in young rats. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. Lead diffusion in monazite

    International Nuclear Information System (INIS)

    Gardes, E.

    2006-06-01

    Proper knowledge of the diffusion rates of lead in monazite is necessary to understand the U-Th-Pb age anomalies of this mineral, which is one of the most used in geochronology after zircon. Diffusion experiments were performed in NdPO 4 monocrystals and in Nd 0.66 Ca 0.17 Th 0.17 PO 4 polycrystals from Nd 0.66 Pb 0.17 Th 0.17 PO 4 thin films to investigate Pb 2+ + Th 4+ ↔ 2 Nd 3+ and Pb 2+ ↔ Ca 2+ exchanges. Diffusion annealings were run between 1200 and 1500 Celsius degrees, at room pressure, for durations ranging from one hour to one month. The diffusion profiles were analysed using TEM (transmission electronic microscopy) and RBS (Rutherford backscattering spectroscopy). The diffusivities extracted for Pb 2+ + Th 4+ ↔ 2 Nd 3+ exchange follow an Arrhenius law with parameters E equals 509 ± 24 kJ mol -1 and log(D 0 (m 2 s -1 )) equals -3.41 ± 0.77. Preliminary data for Pb 2+ ↔ Ca 2+ exchange are in agreement with this result. The extrapolation of our data to crustal temperatures yields very slow diffusivities. For instance, the time necessary for a 50 μm grain to lose all of its lead at 800 Celsius degrees is greater than the age of the Earth. From these results and other evidence from the literature, we conclude that most of the perturbations in U-Th-Pb ages of monazite cannot be attributed to lead diffusion, but rather to interactions with fluids. (author)

  12. Leading change: 2--planning.

    Science.gov (United States)

    Kerridge, Joanna

    National initiatives have outlined the importance of involving frontline staff in service improvement, and the ability to influence and manage change has been identified as an essential skill for delivering new models of care. Nurses often have to take the lead in managing change in clinical practice. The second in a three-part series is designed to help nurses at all levels develop the knowledge and skills to function as change agents within their organisations. This article focuses on planning the change and dealing with resistance.

  13. lead glass brick

    CERN Multimedia

    When you look through the glass at a picture behind, the picture appears raised up because light is slowed down in the dense glass. It is this density (4.06 gcm-3) that makes lead glass attractive to physicists. The refractive index of the glass is 1.708 at 400nm (violet light), meaning that light travels in the glass at about 58% its normal speed. At CERN, the OPAL detector uses some 12000 blocks of glass like this to measure particle energies.

  14. Altered pain responses in abstinent (±)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") users.

    Science.gov (United States)

    McCann, Una D; Edwards, Robert R; Smith, Michael T; Kelley, Kristen; Wilson, Michael; Sgambati, Francis; Ricaurte, George

    2011-10-01

    (±)3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug that has potential to damage brain serotonin (5-HT) neurons in humans. Brain 5-HT neurons play a role in pain modulation, yet little is known about long-term effects of MDMA on pain function. Notably, MDMA users have been shown to have altered sleep, a phenomenon that can lead to altered pain modulation. This study sought to assess pain processing in MDMA users using objective methods, and explore potential relationships between pain processing and sleep indices. Forty-two abstinent MDMA users and 43 age-matched controls participated in a 5-day inpatient study. Outcome measures included standardized measures of pain, sleep polysomnograms, and power spectral measures of the sleep EEG. When differences in psychophysiological measures of pain were found, the relationship between pain and sleep measures was explored. MDMA users demonstrated lower pressure pain thresholds, increased cold pain ratings, increased pain ratings during testing of diffuse noxious inhibitory control, and decreased Stage 2 sleep. Numerous significant relationships between sleep and pain measures were identified, but differences in sleep between the two groups were not found to mediate altered pain perception in MDMA users. Abstinent MDMA users have altered pain perception and sleep architecture. Although pain and sleep outcomes were related, differences in sleep architecture in MDMA users did not mediate altered pain responses. It remains to be determined whether alterations in pain perception in MDMA users are secondary to neurotoxicity of 5-HT-mediated pain pathways or alterations in other brain processes that modulate pain perception.

  15. Device including a contact detector

    DEFF Research Database (Denmark)

    2011-01-01

    The present invention relates to a probe for determining an electrical property of an area of a surface of a test sample, the probe is intended to be in a specific orientation relative to the test sample. The probe may comprise a supporting body defining a first surface. A plurality of cantilever...... of cantilever arms (12) contacting the surface of the test sample when performing the movement....... arms (12) may extend from the supporting body in co-planar relationship with the first surface. The plurality of cantilever arms (12) may extend substantially parallel to each other and each of the plurality of cantilever arms (12) may include an electrical conductive tip for contacting the area...

  16. Alteration in insulin action

    DEFF Research Database (Denmark)

    Tanti, J F; Gual, P; Grémeaux, T

    2004-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS......-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine...... to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases...

  17. Alteration in insulin action

    DEFF Research Database (Denmark)

    Tanti, J F; Gual, P; Grémeaux, T

    2004-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS...... to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases......-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine...

  18. Sulphur depletion altered somatic embryogenesis in Theobroma ...

    African Journals Online (AJOL)

    Somatic embryogenesis is a useful tool for Theobroma cacao improvement and propagation. Depending on culture medium composition, different morphogenetic structures (including somatic embryo) occur in response to alteration of genes expression patterns and biochemical changes. The effect of SO42- ion deficiency ...

  19. Lead and Copper Control 101-slides

    Science.gov (United States)

    This presentation is an overview of the most important water treatment strategies for the control of lead and copper release from drinking water corrosion. In addition to the sections specifically on lead and copper treatment, sections are included that cover sampling to find le...

  20. Relational Leading and Dialogic Process

    DEFF Research Database (Denmark)

    Hansen, Lone Hersted

    The Ph.D. thesis contributes to a relational orientation to leading, emphasizing leadership as a shared, collaborative and co-creative activity. In this paradigm major emphasis is put on dialogue and interaction. Inspired by social constructionist ideas, the thesis considers approaches to learning...... with the thesis, dialogically based practices inspired by action research with the aim to enhance collaborative knowledge building, reflexivity and dialogical skills in groups and teams were carried out, analyzed and documented. Participants included school principals, leaders of kindergartens, teachers...

  1. Eryptosis in lead-exposed workers

    Energy Technology Data Exchange (ETDEWEB)

    Aguilar-Dorado, Itzel-Citlalli [Biochemistry Department, Centro de Investigación y Estudios Avanzados IPN, México, DF (Mexico); Hernández, Gerardo [Section of Methodology of Science, Centro de Investigación y Estudios Avanzados IPN, México, DF (Mexico); Quintanar-Escorza, Martha-Angelica [Faculty of Medicine, UJED, Durango, DGO (Mexico); Maldonado-Vega, María [CIATEC, León, GTO (Mexico); Rosas-Flores, Margarita [Biochemistry Department, Centro de Investigación y Estudios Avanzados IPN, México, DF (Mexico); Calderón-Salinas, José-Víctor, E-mail: jcalder@cinvestav.mx [Biochemistry Department, Centro de Investigación y Estudios Avanzados IPN, México, DF (Mexico)

    2014-12-01

    Eryptosis is a physiological phenomenon in which old and damaged erythrocytes are removed from circulation. Erythrocytes incubated with lead have exhibited major eryptosis. In the present work we found evidence of high levels of eryptosis in lead exposed workers possibly via oxidation. Blood samples were taken from 40 male workers exposed to lead (mean blood lead concentration 64.8 μg/dl) and non-exposed workers (4.2 μg/dl). The exposure to lead produced an intoxication characterized by 88.3% less δ-aminolevulinic acid dehydratase (δALAD) activity in lead exposed workers with respect to non-lead exposed workers. An increment of oxidation in lead exposed workers was characterized by 2.4 times higher thiobarbituric acid-reactive substance (TBARS) concentration and 32.8% lower reduced/oxidized glutathione (GSH/GSSG) ratio. Oxidative stress in erythrocytes of lead exposed workers is expressed in 192% higher free calcium concentration [Ca{sup 2+}]{sub i} and 1.6 times higher μ-calpain activity with respect to non-lead exposed workers. The adenosine triphosphate (ATP) concentration was not significantly different between the two worker groups. No externalization of phosphatidylserine (PS) was found in non-lead exposed workers (< 0.1%), but lead exposed workers showed 2.82% externalization. Lead intoxication induces eryptosis possibly through a molecular pathway that includes oxidation, depletion of reduced glutathione (GSH), increment of [Ca{sup 2+}], μ-calpain activation and externalization of PS in erythrocytes. Identifying molecular signals that induce eryptosis in lead intoxication is necessary to understand its physiopathology and chronic complications. - Graphical abstract: Fig. 1. (A) Blood lead concentration (PbB) and (B) phosphatidylserine externalization on erythrocyte membranes of non-lead exposed (□) and lead exposed workers (■). Values are mean ± SD. *Significantly different (P < 0.001). - Highlights: • Erythrocytes of lead exposed workers

  2. High risk of lead contamination for scavengers in an area with high moose hunting success.

    Directory of Open Access Journals (Sweden)

    Pierre Legagneux

    Full Text Available Top predators and scavengers are vulnerable to pollutants, particularly those accumulated along the food chain. Lead accumulation can induce severe disorders and alter survival both in mammals (including humans and in birds. A potential source of lead poisoning in wild animals, and especially in scavengers, results from the consumption of ammunition residues in the tissues of big game killed by hunters. For two consecutive years we quantified the level lead exposure in individuals of a sentinel scavenger species, the common raven (Corvus corax, captured during the moose (Alces alces hunting season in eastern Quebec, Canada. The source of the lead contamination was also determined using stable isotope analyses. Finally, we identified the different scavenger species that could potentially be exposed to lead by installing automatic cameras targeting moose gut piles. Blood lead concentration in ravens increased over time, indicating lead accumulation over the moose-hunting season. Using a contamination threshold of 100 µg x L(-1, more than 50% of individuals were lead-contaminated during the moose hunting period. Lead concentration was twice as high in one year compared to the other, matching the number of rifle-shot moose in the area. Non-contaminated birds exhibited no ammunition isotope signatures. The isotope signature of the lead detected in contaminated ravens tended towards the signature from lead ammunition. We also found that black bears (Ursus americanus, golden eagles and bald eagles (Aquila chrysaetos and Haliaeetus leucocephalus, two species of conservation concern scavenged heavily on moose viscera left by hunters. Our unequivocal results agree with other studies and further motivate the use of non-toxic ammunition for big game hunting.

  3. High risk of lead contamination for scavengers in an area with high moose hunting success.

    Science.gov (United States)

    Legagneux, Pierre; Suffice, Pauline; Messier, Jean-Sébastien; Lelievre, Frédérick; Tremblay, Junior A; Maisonneuve, Charles; Saint-Louis, Richard; Bêty, Joël

    2014-01-01

    Top predators and scavengers are vulnerable to pollutants, particularly those accumulated along the food chain. Lead accumulation can induce severe disorders and alter survival both in mammals (including humans) and in birds. A potential source of lead poisoning in wild animals, and especially in scavengers, results from the consumption of ammunition residues in the tissues of big game killed by hunters. For two consecutive years we quantified the level lead exposure in individuals of a sentinel scavenger species, the common raven (Corvus corax), captured during the moose (Alces alces) hunting season in eastern Quebec, Canada. The source of the lead contamination was also determined using stable isotope analyses. Finally, we identified the different scavenger species that could potentially be exposed to lead by installing automatic cameras targeting moose gut piles. Blood lead concentration in ravens increased over time, indicating lead accumulation over the moose-hunting season. Using a contamination threshold of 100 µg x L(-1), more than 50% of individuals were lead-contaminated during the moose hunting period. Lead concentration was twice as high in one year compared to the other, matching the number of rifle-shot moose in the area. Non-contaminated birds exhibited no ammunition isotope signatures. The isotope signature of the lead detected in contaminated ravens tended towards the signature from lead ammunition. We also found that black bears (Ursus americanus), golden eagles and bald eagles (Aquila chrysaetos and Haliaeetus leucocephalus, two species of conservation concern) scavenged heavily on moose viscera left by hunters. Our unequivocal results agree with other studies and further motivate the use of non-toxic ammunition for big game hunting.

  4. Genome profiling of chronic myelomonocytic leukemia: frequent alterations of RAS and RUNX1 genes

    Directory of Open Access Journals (Sweden)

    Olschwang Sylviane

    2008-10-01

    Full Text Available Abstract Background Chronic myelomonocytic leukemia (CMML is a hematological disease close to, but separate from both myeloproliferative disorders (MPD and myelodysplastic syndromes and may show either myeloproliferative (MP-CMML or myelodysplastic (MD-CMML features. Not much is known about the molecular biology of this disease. Methods We studied a series of 30 CMML samples (13 MP- and 11 MD-CMMLs, and 6 acutely transformed cases from 29 patients by using Agilent high density array-comparative genomic hybridization (aCGH and sequencing of 12 candidate genes. Results Two-thirds of samples did not show any obvious alteration of aCGH profiles. In one-third we observed chromosome abnormalities (e.g. trisomy 8, del20q and gain or loss of genes (e.g. NF1, RB1 and CDK6. RAS mutations were detected in 4 cases (including an uncommon codon 146 mutation in KRAS and PTPN11 mutations in 3 cases. We detected 11 RUNX1 alterations (9 mutations and 2 rearrangements. The rearrangements were a new, cryptic inversion of chromosomal region 21q21-22 leading to break and fusion of RUNX1 to USP16. RAS and RUNX1 alterations were not mutually exclusive. RAS pathway mutations occurred in MP-CMMLs (~46% but not in MD-CMMLs. RUNX1 alterations (mutations and cryptic rearrangement occurred in both MP and MD classes (~38%. Conclusion We detected RAS pathway mutations and RUNX1 alterations. The latter included a new cryptic USP16-RUNX1 fusion. In some samples, two alterations coexisted already at this early chronic stage.

  5. Genome profiling of chronic myelomonocytic leukemia: frequent alterations of RAS and RUNX1 genes

    International Nuclear Information System (INIS)

    Gelsi-Boyer, Véronique; Bentires-Alj, Mohamed; Olschwang, Sylviane; Vey, Norbert; Mozziconacci, Marie-Joëlle; Birnbaum, Daniel; Chaffanet, Max; Trouplin, Virginie; Adélaïde, José; Aceto, Nicola; Remy, Virginie; Pinson, Stephane; Houdayer, Claude; Arnoulet, Christine; Sainty, Danielle

    2008-01-01

    Chronic myelomonocytic leukemia (CMML) is a hematological disease close to, but separate from both myeloproliferative disorders (MPD) and myelodysplastic syndromes and may show either myeloproliferative (MP-CMML) or myelodysplastic (MD-CMML) features. Not much is known about the molecular biology of this disease. We studied a series of 30 CMML samples (13 MP- and 11 MD-CMMLs, and 6 acutely transformed cases) from 29 patients by using Agilent high density array-comparative genomic hybridization (aCGH) and sequencing of 12 candidate genes. Two-thirds of samples did not show any obvious alteration of aCGH profiles. In one-third we observed chromosome abnormalities (e.g. trisomy 8, del20q) and gain or loss of genes (e.g. NF1, RB1 and CDK6). RAS mutations were detected in 4 cases (including an uncommon codon 146 mutation in KRAS) and PTPN11 mutations in 3 cases. We detected 11 RUNX1 alterations (9 mutations and 2 rearrangements). The rearrangements were a new, cryptic inversion of chromosomal region 21q21-22 leading to break and fusion of RUNX1 to USP16. RAS and RUNX1 alterations were not mutually exclusive. RAS pathway mutations occurred in MP-CMMLs (~46%) but not in MD-CMMLs. RUNX1 alterations (mutations and cryptic rearrangement) occurred in both MP and MD classes (~38%). We detected RAS pathway mutations and RUNX1 alterations. The latter included a new cryptic USP16-RUNX1 fusion. In some samples, two alterations coexisted already at this early chronic stage

  6. Lead and Your Baby

    Science.gov (United States)

    ... at a healthy weight and avoiding alcohol and street drugs . Featured articles March of Dimes Premature Birth ... and around homes in the United States include: Arts and crafts supplies, like oil paint, ceramic glazes ...

  7. MYC leads the way.

    Science.gov (United States)

    Venkateswaran, Niranjan; Conacci-Sorrell, Maralice

    2017-11-25

    Members of the MYC family of proto-oncogenes are the most commonly deregulated genes in all human cancers. MYC proteins drive an increase in cellular proliferation and facilitate multiple aspects of tumor initiation and progression, thereby controlling all hallmarks of cancer. MYC's ability to drive metabolic reprogramming of tumor cells leading to biomass accumulation and cellular proliferation is the most studied function of these oncogenes. MYC also regulates tumor progression and is often implicated in resistance to chemotherapy and in metastasis. While most oncogenic functions of MYC are attributed to its role as a transcription factor, more recently, new roles of MYC as a pro-survival factor in the cytoplasm suggest a previously unappreciated diversity in MYC's roles in cancer progression. This review will focus on the role of MYC in invasion and will discuss the canonical functions of MYC in Epithelial to Mesenchymal Transition and the cytoplasmic functions of MYC-nick in collective migration.

  8. Lightweight, durable lead-acid batteries

    Science.gov (United States)

    Lara-Curzio, Edgar; An, Ke; Kiggans, Jr., James O; Dudney, Nancy J; Contescu, Cristian I; Baker, Frederick S; Armstrong, Beth L

    2013-05-21

    A lightweight, durable lead-acid battery is disclosed. Alternative electrode materials and configurations are used to reduce weight, to increase material utilization and to extend service life. The electrode can include a current collector having a buffer layer in contact with the current collector and an electrochemically active material in contact with the buffer layer. In one form, the buffer layer includes a carbide, and the current collector includes carbon fibers having the buffer layer. The buffer layer can include a carbide and/or a noble metal selected from of gold, silver, tantalum, platinum, palladium and rhodium. When the electrode is to be used in a lead-acid battery, the electrochemically active material is selected from metallic lead (for a negative electrode) or lead peroxide (for a positive electrode).

  9. Cerebrospinal fluid space alterations in melancholic depression.

    Directory of Open Access Journals (Sweden)

    Esther Via

    Full Text Available Melancholic depression is a biologically homogeneous clinical entity in which structural brain alterations have been described. Interestingly, reports of structural alterations in melancholia include volume increases in Cerebro-Spinal Fluid (CSF spaces. However, there are no previous reports of CSF volume alterations using automated whole-brain voxel-wise approaches, as tissue classification algorithms have been traditionally regarded as less reliable for CSF segmentation. Here we aimed to assess CSF volumetric alterations in melancholic depression and their clinical correlates by means of a novel segmentation algorithm ('new segment', as implemented in the software Statistical Parametric Mapping-SPM8, incorporating specific features that may improve CSF segmentation. A three-dimensional Magnetic Resonance Image (MRI was obtained from seventy patients with melancholic depression and forty healthy control subjects. Although imaging data were pre-processed with the 'new segment' algorithm, in order to obtain a comparison with previous segmentation approaches, tissue segmentation was also performed with the 'unified segmentation' approach. Melancholic patients showed a CSF volume increase in the region of the left Sylvian fissure, and a CSF volume decrease in the subarachnoid spaces surrounding medial and lateral parietal cortices. Furthermore, CSF increases in the left Sylvian fissure were negatively correlated with the reduction percentage of depressive symptoms at discharge. None of these results were replicated with the 'unified segmentation' approach. By contrast, between-group differences in the left Sylvian fissure were replicated with a non-automated quantification of the CSF content of this region. Left Sylvian fissure alterations reported here are in agreement with previous findings from non-automated CSF assessments, and also with other reports of gray and white matter insular alterations in depressive samples using automated approaches

  10. Potential for Lead Release from Lead-Immobilized Animal Manure Compost in Rhizosphere Soil of Shooting Range

    Directory of Open Access Journals (Sweden)

    Masahiko Katoh

    2016-01-01

    Full Text Available This study aimed to clarify the magnitude of lead release from lead-sorbed animal manure compost (AMC in rhizosphere soil compared with nonplanted soil of shooting range. The presence of buckwheat caused reduction in rhizosphere soil pH and enhancement in the level of water-soluble organic carbon compared with those of nonplanted soil. In addition, the presence of buckwheat altered the lead phases and increased the relative amount of the soluble exchangeable fraction, resulting in increase in the CaCl2-soluble lead level. In contrast, the presence of Guinea grass did not change the lead bioavailability or phases compared with nonplanted soil. Lead release tests in solution showed that between solution pH 5 and solution pH 7 the amount of lead released from the compost was higher in the rhizosphere soil of buckwheat than in nonplanted soil, whereas there was no significant difference between the rhizosphere soil of Guinea grass and nonplanted soil. These results suggest that the increase in the quantity of exchangeable lead resulting from the rhizosphere effect induces lead immobilized by the AMC to be remobilized. Therefore, AMC should be applied to soils that contain plants that are unable to alter the lead phases in the shooting range soil. Efforts should be particularly made to ensure that lead cannot be transformed to the exchangeable phase.

  11. Molecular alterations and biomarkers in colorectal cancer

    Science.gov (United States)

    Grady, William M.; Pritchard, Colin C.

    2013-01-01

    The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

  12. Lead (Environmental Health Student Portal)

    Science.gov (United States)

    ... Pesticides Climate Change Climate Change Home What is Climate Change ... Lead The Basics Lead is a soft, bluish-white metal that exists naturally in the environment. When lead combines with other chemical elements, it ...

  13. Music alters visual perception.

    Science.gov (United States)

    Jolij, Jacob; Meurs, Maaike

    2011-04-21

    Visual perception is not a passive process: in order to efficiently process visual input, the brain actively uses previous knowledge (e.g., memory) and expectations about what the world should look like. However, perception is not only influenced by previous knowledge. Especially the perception of emotional stimuli is influenced by the emotional state of the observer. In other words, how we perceive the world does not only depend on what we know of the world, but also by how we feel. In this study, we further investigated the relation between mood and perception. We let observers do a difficult stimulus detection task, in which they had to detect schematic happy and sad faces embedded in noise. Mood was manipulated by means of music. We found that observers were more accurate in detecting faces congruent with their mood, corroborating earlier research. However, in trials in which no actual face was presented, observers made a significant number of false alarms. The content of these false alarms, or illusory percepts, was strongly influenced by the observers' mood. As illusory percepts are believed to reflect the content of internal representations that are employed by the brain during top-down processing of visual input, we conclude that top-down modulation of visual processing is not purely predictive in nature: mood, in this case manipulated by music, may also directly alter the way we perceive the world.

  14. Music alters visual perception.

    Directory of Open Access Journals (Sweden)

    Jacob Jolij

    Full Text Available BACKGROUND: Visual perception is not a passive process: in order to efficiently process visual input, the brain actively uses previous knowledge (e.g., memory and expectations about what the world should look like. However, perception is not only influenced by previous knowledge. Especially the perception of emotional stimuli is influenced by the emotional state of the observer. In other words, how we perceive the world does not only depend on what we know of the world, but also by how we feel. In this study, we further investigated the relation between mood and perception. METHODS AND FINDINGS: We let observers do a difficult stimulus detection task, in which they had to detect schematic happy and sad faces embedded in noise. Mood was manipulated by means of music. We found that observers were more accurate in detecting faces congruent with their mood, corroborating earlier research. However, in trials in which no actual face was presented, observers made a significant number of false alarms. The content of these false alarms, or illusory percepts, was strongly influenced by the observers' mood. CONCLUSIONS: As illusory percepts are believed to reflect the content of internal representations that are employed by the brain during top-down processing of visual input, we conclude that top-down modulation of visual processing is not purely predictive in nature: mood, in this case manipulated by music, may also directly alter the way we perceive the world.

  15. Altered brain activity for phonological manipulation in dyslexic Japanese children.

    Science.gov (United States)

    Kita, Yosuke; Yamamoto, Hisako; Oba, Kentaro; Terasawa, Yuri; Moriguchi, Yoshiya; Uchiyama, Hitoshi; Seki, Ayumi; Koeda, Tatsuya; Inagaki, Masumi

    2013-12-01

    Because of unique linguistic characteristics, the prevalence rate of developmental dyslexia is relatively low in the Japanese language. Paradoxically, Japanese children have serious difficulty analysing phonological processes when they have dyslexia. Neurobiological deficits in Japanese dyslexia remain unclear and need to be identified, and may lead to better understanding of the commonality and diversity in the disorder among different linguistic systems. The present study investigated brain activity that underlies deficits in phonological awareness in Japanese dyslexic children using functional magnetic resonance imaging. We developed and conducted a phonological manipulation task to extract phonological processing skills and to minimize the influence of auditory working memory on healthy adults, typically developing children, and dyslexic children. Current experiments revealed that several brain regions participated in manipulating the phonological information including left inferior and middle frontal gyrus, left superior temporal gyrus, and bilateral basal ganglia. Moreover, dyslexic children showed altered activity in two brain regions. They showed hyperactivity in the basal ganglia compared with the two other groups, which reflects inefficient phonological processing. Hypoactivity in the left superior temporal gyrus was also found, suggesting difficulty in composing and processing phonological information. The altered brain activity shares similarity with those of dyslexic children in countries speaking alphabetical languages, but disparity also occurs between these two populations. These are initial findings concerning the neurobiological impairments in dyslexic Japanese children.

  16. Lead exposure in two pottery handicraft populations.

    Science.gov (United States)

    Molina-Ballesteros, G; Zuñiga-Charles, M A; García-de Alba, J E; Cárdenas-Ortega, A; Solis-Camara, P

    1980-01-01

    Lead poisoning studies were carried out in the populations of two potter towns in the State of Jalisco, Mexico. The first population in Tonalá included 198 people who use lead monoxide (PbO) in making pottery. The second population in El Rosario included 187 people who do not use any lead salt in the pottery-making process. The studies included children, adolescents and adults of both sexes. Analyses for lead in the blood (Pb-B), hemoglobin (Hb), hematocrit (Ht), and urinary delta-aminolevulinic acid (ALA U) were carried out. In the population exposed to lead, abnormally high lead concentrations in blood and urinary delta-aminolevulinic acid were found in both sexes and in all age groups studied. When compared to the control group, the differences are statistically significant. The Hb and Ht results fell within the lower normal limits in both populations. No cases of acute lead poisoning were found, but the high amount of lead absorption in the Tonalá population may be caused by the rudimentary means of manufacturing their products.

  17. Impact of developmental lead exposure on splenic factors

    International Nuclear Information System (INIS)

    Kasten-Jolly, Jane; Heo, Yong; Lawrence, David A.

    2010-01-01

    Lead (Pb) is known to alter the functions of numerous organ systems, including the hematopoietic and immune systems. Pb can induce anemia and can lower host resistance to bacterial and viral infections. The anemia is due to Pb's inhibition of hemoglobin synthesis and Pb's induction of membrane changes, leading to early erythrocyte senescence. Pb also increases B-cell activation/proliferation and skews T-cell help (Th) toward Th2 subset generation. The specific mechanisms for many of the Pb effects are, as yet, not completely understood. Therefore, we performed gene expression analysis, via microarray, on RNA from the spleens of developmentally Pb-exposed mice, in order to gain further insight into these Pb effects. Splenic RNA microarray analysis indicated strong up-regulation of genes coding for proteolytic enzymes, lipases, amylase, and RNaseA. The data also showed that Pb affected the expression of many genes associated with innate immunity. Analysis of the microarray results via GeneSifter software indicated that Pb increased apoptosis, B-cell differentiation, and Th2 development. Direct up-regulation by Pb of expression of the gene encoding the heme-regulated inhibitor (HRI) suggested that Pb can decrease erythropoiesis by blocking globin mRNA translation. Pb's high elevation of digestive/catabolizing enzymes could generate immunogenic self peptides. With Pb's potential to induce new self-peptides and to enhance the expression of caspases, cytokines, and other immunomodulators, further evaluation of Pb's involvement in autoimmune phenomena, especially Th2-mediated autoantibody production, and alteration of organ system activities is warranted.

  18. Exploring How Lead Users Develop Radical Innovation

    DEFF Research Database (Denmark)

    Lettl, Christopher; Hienerth, Christoph; Gemuenden, Hans Georg

    2008-01-01

    In this study, we explore how lead users develop radical innovations outside of manufacturing firms. We analyze the transition from a very early stage of activities to the ultimate commercialization of these innovations. The focus in this context is on the initiatives undertaken by lead users...... lead users as surgeons launch entrepreneurial activities and bridge periods in which established medical equipment manufacturers would not risk investing in radical innovations. By doing so, lead users create the conditions usually provided in manufacturer-initiated lead user projects, including...... the supply of diversified knowledge, the development and coordination of a network for further development of the innovation, and initial tests of technical or market feasibility. Our findings have implications for manufacturing firms that wish to design radical innovation projects with (individual) lead...

  19. Solubility of iron in liquid lead

    International Nuclear Information System (INIS)

    Ali-Khan, I.

    1981-01-01

    The use of liquid lead in high temperature chemical and metallurgical processes is well known. The structural materials applied for the containment of these processes are either iron base alloys or possess iron as an alloying element. Besides that, lead itself is alloyed in some steels to achieve some very useful properties. For understanding the effect of liquid lead in such structural materials, it is important to determine the solubility of iron in liquid lead which would also be indicative of the stability of these alloys. At the institute of reactor materials of KFA Juelich, investigations have been conducted to determine the solubility of iron in liquid lead up to a temperature of about 1000 0 C. In this presentation the data concerning the solubility of iron in liquid lead are brought up to date and discussed including the results of our previous investigations. (orig.)

  20. Apparatus and methods for purifying lead

    Science.gov (United States)

    Tunison, Harmon M.

    2016-01-12

    Disclosed is an exemplary method of purifying lead which includes the steps of placing lead and a fluoride salt blend in a container; forming a first fluid of molten lead at a first temperature; forming a second fluid of the molten fluoride salt blend at a second temperature higher than the first temperature; mixing the first fluid and the second fluid together; separating the two fluids; solidifying the molten fluoride salt blend at a temperature above a melting point of the lead; and removing the molten lead from the container. In certain exemplary methods the molten lead is removed from the container by decanting. In still other exemplary methods the molten salt blend is a Lewis base fluoride eutectic salt blend, and in yet other exemplary methods the molten salt blend contains sodium fluoride, lithium fluoride, and potassium fluoride.

  1. Altered gut microbiota in Rett syndrome.

    Science.gov (United States)

    Strati, Francesco; Cavalieri, Duccio; Albanese, Davide; De Felice, Claudio; Donati, Claudio; Hayek, Joussef; Jousson, Olivier; Leoncini, Silvia; Pindo, Massimo; Renzi, Daniela; Rizzetto, Lisa; Stefanini, Irene; Calabrò, Antonio; De Filippo, Carlotta

    2016-07-30

    The human gut microbiota directly affects human health, and its alteration can lead to gastrointestinal abnormalities and inflammation. Rett syndrome (RTT), a progressive neurological disorder mainly caused by mutations in MeCP2 gene, is commonly associated with gastrointestinal dysfunctions and constipation, suggesting a link between RTT's gastrointestinal abnormalities and the gut microbiota. The aim of this study was to evaluate the bacterial and fungal gut microbiota in a cohort of RTT subjects integrating clinical, metabolomics and metagenomics data to understand if changes in the gut microbiota of RTT subjects could be associated with gastrointestinal abnormalities and inflammatory status. Our findings revealed the occurrence of an intestinal sub-inflammatory status in RTT subjects as measured by the elevated values of faecal calprotectin and erythrocyte sedimentation rate. We showed that, overall, RTT subjects harbour bacterial and fungal microbiota altered in terms of relative abundances from those of healthy controls, with a reduced microbial richness and dominated by microbial taxa belonging to Bifidobacterium, several Clostridia (among which Anaerostipes, Clostridium XIVa, Clostridium XIVb) as well as Erysipelotrichaceae, Actinomyces, Lactobacillus, Enterococcus, Eggerthella, Escherichia/Shigella and the fungal genus Candida. We further observed that alterations of the gut microbiota do not depend on the constipation status of RTT subjects and that this dysbiotic microbiota produced altered short chain fatty acids profiles. We demonstrated for the first time that RTT is associated with a dysbiosis of both the bacterial and fungal component of the gut microbiota, suggesting that impairments of MeCP2 functioning favour the establishment of a microbial community adapted to the costive gastrointestinal niche of RTT subjects. The altered production of short chain fatty acids associated with this microbiota might reinforce the constipation status of RTT

  2. The Lead Partner Playbook

    Science.gov (United States)

    Kim, Ji Hea Jay

    2012-01-01

    Help Wanted: Innovative, strategic-thinking entrepreneurs to turn around groups of low-performing schools. Competitive benefits, including working in newly formed operating units with charter-like autonomy, access to district's back-office resources and buildings, $3.5 billion federal money, and opportunity to transform schools for hundreds of…

  3. [Environmental lead poisoning from lead-glazed earthenware used for storing drinks].

    Science.gov (United States)

    Sabouraud, S; Coppéré, B; Rousseau, C; Testud, F; Pulce, C; Tholly, F; Blanc, M; Culoma, F; Facchin, A; Ninet, J; Chambon, P; Medina, B; Descotes, J

    2009-12-01

    Current unusual environmental sources of lead exposure mainly include traditional medicines, either ayurvedic remedies or others, traditional cosmetics (kohl, surma), and the use of traditional earthenware, for storage or cooking. We report two cases of lead poisoning in adults initially identified by paroxysmal abdominal pain or anemia. In both cases, the environmental investigation evidenced one main source of lead exposure, namely a lead-glazed earthenware jug in which a drink was stored, "kefir" in the first case, and "kombucha" tea in the second one. It is recommended to search for lead intoxication in patients with unexplained anemia. Environmental sources of lead can be multiple. Their relative importance has to be ranked during the environmental investigation and among these, lead-glazed earthenware must be considered as a source of high lead exposure when drinks are stored inside and thus can soak.

  4. Corrosion by liquid lead and lead-bismuth: experimental results review and analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jinsuo [Los Alamos National Laboratory

    2008-01-01

    Liquid metal technologies for liquid lead and lead-bismuth alloy are under wide investigation and development for advanced nuclear energy systems and waste transmutation systems. Material corrosion is one of the main issues studied a lot recently in the development of the liquid metal technology. This study reviews corrosion by liquid lead and lead bismuth, including the corrosion mechanisms, corrosion inhibitor and the formation of the protective oxide layer. The available experimental data are analyzed by using a corrosion model in which the oxidation and scale removal are coupled. Based on the model, long-term behaviors of steels in liquid lead and lead-bismuth are predictable. This report provides information for the selection of structural materials for typical nuclear reactor coolant systems when selecting liquid lead or lead bismuth as heat transfer media.

  5. pXRF and IR Fluorescence Imaging Studies of CdS Alteration in Paintings by Edvard Munch and Henri Matisse in Oslo, Copenhagen, and San Francisco

    DEFF Research Database (Denmark)

    Vila, Anna; Wadum, Jørgen; Mass, Jennifer

    2014-01-01

    The identification of altered cadmium yellow paints in early modernist works is critical to their stabilization and to the long term preservation of the paintings in which they occur. The identification of incipient photo-alteration of these pigments, before there is visual evidence...... of their chemical degradation, is of particular concern. The alteration of these pigments causes chalking, flaking, fading, and darkening of the yellow paints, leading to irreversible changes in the physical and chemical structure of the paint layer, and dramatically altering the appearance of the work. Standoff......-induced visible fluorescence; ultraviolet-induced infrared fluorescence; multispectral imaging; and x-ray fluorescence. Questions addressed included: is the imaging method being tested comprehensive? Is it efficient at surveying an entire painting? Does it reveal the state of preservation of the pigment? Does...

  6. Leading Your Leaders

    Science.gov (United States)

    Hale, Wayne N.

    2008-01-01

    life is good. More often when an unbelievably difficult test fails, we are left with a very long discussion of why and what was wrong in the design or execution of the test. Make sure that the test is well defined. Even then, it is important to explain to your leaders what inherent accuracy (or error) the test conditions or equipment have and what the assumptions or initial conditions were for the test. Test results without a good understanding of the test's accuracy or the pedigree of the test assumptions are worth very little. Finally, there is flight test data. Always limited, never at the edge of the envelope, it still shows how the real hardware works in a combined environment. Flight experience is dangerous because it typically doesn't show how close to the edge of the cliff the equipment is operating, but it does demonstrate how the hardware really works. A flight test is the ultimate test, again taken with the knowledge that it is probably not the extreme but something more like the middle of the environmental and systems performance. Good understanding of a problem and its solution always relies on a combination of all these methods. Be sure to lead your leaders by using all the tools you have at your disposal. At the end of the day, decisions in space flight always come down to a risk trade. Our business is not remotely safe, not in the sense that the public, the media, or our legislators use the term. Everything we do has a risk, cost, schedule, or performance trade-off. For your leaders to make an appropriate decision, you need to educate them, lead them, talk with them, and engage them in the discussion until full understanding takes place. It's your job. *

  7. Can Molecular Hippocampal Alterations Explain Behavioral ...

    Science.gov (United States)

    Studies in both humans and animals have shown that prenatal stress can alter cognitive function and other neurological behaviors in adult offspring. One possible underlying mechanism for this may lie with alterations in hippocampal gene expression. The present study examined genotypical outcomes in adult male and female offspring of rats exposed to variable stress during pregnancy. Dams (n=15/treatment) were subjected to several non-chemical stressors including intermittent noise, light, crowding, restraint, and altered circadian lighting, from gestational day (GD) 13 to 20. Tail blood was drawn on GD 12, 16 and 20 to verify a stress response. Corticosterone levels were not different between the stressed and non-stressed dams on GD12 but was significantly increased in stressed dams on GD 16 and 20 compared to controls. Dams gave birth on GD22 (postnatal day or PND 0). Several behavioral tests were used to assess the cognitive and behavioral phenotype of the offspring from PND 49 through 86, including the Morris water maze and novel object recognition. Male and female stressed offspring showed reduced reversal learning on the Morris water maze and stressed females did not show a significant preference for the novel object (57 ± 8%) while control females did (71 ± 3%). This indicates altered cognition in prenatally stressed offspring. On PND 91-92, offspring were necropsied and hippocampal tissue was collected. Genotypic outcomes of prenatal stress w

  8. Lead toxicity and nutritional deficiencies

    Energy Technology Data Exchange (ETDEWEB)

    Levander, O.A.

    1979-04-01

    Recent data concerning lead toxicity and nutritional deficiencies are summarized. Lead poisoning can be exacerbated by consumption of either deficient or excessive levels of protein. Mineral deficiencies also exaggerate lead poisoning. Evidence for antagonism between lead and nutritional levels of selenium is inconclusive. Vitamin E deficiency and lead poisoning interact to produce an anemia in rats that is more severe than that caused by either treatment alone. A pro-oxidant stress of lead on red blood cells is hypothesized to cause their accelerated destruction. In addition, disruption of normal membrane structure, leading to peroxidative damage, may occur. Calcium deficiencies in children are negatively correlated with lead concentrations in their blood. Other examples of interactions between minerals and lead poisoning are provided. Nutritional deficiencies have been shown to have an additive effect in potentiating lead toxicity in some cases. (112 references, 4 tables)

  9. Lead content in household paints in India

    International Nuclear Information System (INIS)

    Kumar, Abhay; Gottesfeld, Perry

    2008-01-01

    Lead and its compounds are used in paints not only to impart colour but also to make it durable, corrosion resistant and to improve drying. Adverse health impacts of lead especially on children have led countries to restrict or ban its use in paints. While U.S. and other developed countries instituted measures to limit the use of lead in paints, some developing countries including India have failed to regulate their lead content. The present study was undertaken to determine the levels of lead in new latex (water-based) and enamel paints (oil-based) intended for residential use in India. A total of 69 paint samples (38 latex and 31 enamel samples) from six of the most popular brands were analysed for lead concentrations. While all latex paint samples contained low levels of lead, (i.e., well below 600 ppm as regulated by United States' Consumer Products Safety Commission) the enamel paint samples of all but one brand contained significant concentrations of lead, ranging up to 140,000 ppm. In fact 84% of the enamel paints tested exceeded 600 ppm whereas only 38 % of all samples (including latex and enamel types) exceeded this regulatory level

  10. Contribution of diet to lead exposure among children aged 1 to 7 years in La Plata, Buenos Aires.

    Science.gov (United States)

    Martins, Enrique; Malpeli, Agustina; Asens, Daniel; Telese, Luis; Fasano, Victoria; Vargas, Vania; Tavella, Marina; Colman Lerner, Jorge E

    2018-02-01

    Lead is a toxic metal which, even at low blood levels, can alter normal neurodevelopment in children, so no blood lead level is acceptable. Lead absorption from diet accounts for the highest contribution to blood lead levels in the population who is not exposed to contaminated environments or because of their occupation. The objective of this study was to determine the contribution of diet to lead exposure among children aged 1 to 7 years who attended Hospital de Niños de La Plata for health check-ups. The study was conducted between June 2015 and May 2016. A questionnaire on the frequency of food intake was administered to 91 children whose average age ± standard deviation was 3.0 ± 1.7 years, and foods included in the analysis were selected based on this questionnaire. Selected foods were purchased from different regional stores. Composite samples were made up of different food groups. Lead levels corresponding to each food group were determined and, finally, the daily intake of lead was estimated for the studied population. The daily intake of lead was 138 µg/day. The food groups with the higher intake rates were processed meat products (15.4%), bakery products (14.8%), milk (12.5%), and meat (11.7%). Children aged 1 to 7 years attending a public hospital in La Plata have a lead burden from dietary intake of 138 µg/day. Sociedad Argentina de Pediatría

  11. Numerical simulation of alteration of sodium bentonite by diffusion of ionic groundwater components

    International Nuclear Information System (INIS)

    Jacobsen, J.S.; Carnahan, C.L.

    1987-12-01

    Experiments measuring the movement of trace amounts of radionuclides through compacted bentonite have typically used unaltered bentonite. Models based on experiments such as these may not lead to accurate predictions of the migration through altered or partially altered bentonite of radionuclides that undergo ion exchange. To address this problem, we have modified an existing transport code to include ion exchange and aqueous complexation reactions. The code is thus able to simulate the diffusion of major ionic groundwater components through bentonite and reactions between the bentonite and groundwater. Numerical simulations have been made to investigate the conversion of sodium bentonite to calcium bentonite for a reference groundwater characteristic of deep granitic formations. 20 refs., 2 figs., 2 tabs

  12. The Vestibular-Evoked Postural Response of Adolescents with Idiopathic Scoliosis Is Altered.

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Pialasse

    Full Text Available Adolescent idiopathic scoliosis is a multifactorial disorder including neurological factors. A dysfunction of the sensorimotor networks processing vestibular information could be related to spine deformation. This study investigates whether feed-forward vestibulomotor control or sensory reweighting mechanisms are impaired in adolescent scoliosis patients. Vestibular evoked postural responses were obtained using galvanic vestibular stimulation while participants stood with their eyes closed and head facing forward. Lateral forces under each foot and lateral displacement of the upper body of adolescents with mild (n = 20 or severe (n = 16 spine deformation were compared to those of healthy control adolescents (n = 16. Adolescent idiopathic scoliosis patients demonstrated greater lateral displacement and net lateral forces than controls both during and immediately after vestibular stimulation. Altered sensory reweighting of vestibular and proprioceptive information changed balance control of AIS patients during and after vestibular stimulation. Therefore, scoliosis onset could be related to abnormal sensory reweighting, leading to altered sensorimotor processes.

  13. Glutamate alteration of glutamic acid decarboxylase (GAD) in GABAergic neurons: the role of cysteine proteases.

    Science.gov (United States)

    Monnerie, Hubert; Le Roux, Peter D

    2008-09-01

    Brain cell vulnerability to neurologic insults varies greatly, depending on their neuronal subpopulation. Among cells that survive a pathological insult such as ischemia or brain trauma, some may undergo morphological and/or biochemical changes that could compromise brain function. We previously reported that surviving cortical GABAergic neurons exposed to glutamate in vitro displayed an NMDA receptor (NMDAR)-mediated alteration in the levels of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD65/67) [Monnerie, H., Le Roux, P., 2007. Reduced dendrite growth and altered glutamic acid decarboxylase (GAD) 65- and 67-kDa isoform protein expression from mouse cortical GABAergic neurons following excitotoxic injury in vitro. Exp. Neurol. 205, 367-382]. In this study, we examined the mechanisms by which glutamate excitotoxicity caused a change in cortical GABAergic neurons' GAD protein levels. Removing extracellular calcium prevented the NMDAR-mediated decrease in GAD protein levels, measured using Western blot techniques, whereas inhibiting calcium entry through voltage-gated calcium channels had no effect. Glutamate's effect on GAD protein isoforms was significantly attenuated by preincubation with the cysteine protease inhibitor N-Acetyl-L-Leucyl-L-Leucyl-L-norleucinal (ALLN). Using class-specific protease inhibitors, we observed that ALLN's effect resulted from the blockade of calpain and cathepsin protease activities. Cell-free proteolysis assay confirmed that both proteases were involved in glutamate-induced alteration in GAD protein levels. Together these results suggest that glutamate-induced excitotoxic stimulation of NMDAR in cultured cortical neurons leads to altered GAD protein levels from GABAergic neurons through intracellular calcium increase and protease activation including calpain and cathepsin. Biochemical alterations in surviving cortical GABAergic neurons in various disease states may contribute to the altered balance between excitation

  14. Streamflow alteration at selected sites in Kansas

    Science.gov (United States)

    Juracek, Kyle E.; Eng, Ken

    2017-06-26

    An understanding of streamflow alteration in response to various disturbances is necessary for the effective management of stream habitat for a variety of species in Kansas. Streamflow alteration can have negative ecological effects. Using a modeling approach, streamflow alteration was assessed for 129 selected U.S. Geological Survey streamgages in the State for which requisite streamflow and basin-characteristic information was available. The assessment involved a comparison of the observed condition from 1980 to 2015 with the predicted expected (least-disturbed) condition for 29 streamflow metrics. The metrics represent various characteristics of streamflow including average flow (annual, monthly) and low and high flow (frequency, duration, magnitude).Streamflow alteration in Kansas was indicated locally, regionally, and statewide. Given the absence of a pronounced trend in annual precipitation in Kansas, a precipitation-related explanation for streamflow alteration was not supported. Thus, the likely explanation for streamflow alteration was human activity. Locally, a flashier flow regime (typified by shorter lag times and more frequent and higher peak discharges) was indicated for three streamgages with urbanized basins that had higher percentages of impervious surfaces than other basins in the State. The combination of localized reservoir effects and regional groundwater pumping from the High Plains aquifer likely was responsible, in part, for diminished conditions indicated for multiple streamflow metrics in western and central Kansas. Statewide, the implementation of agricultural land-management practices to reduce runoff may have been responsible, in part, for a diminished duration and magnitude of high flows. In central and eastern Kansas, implemented agricultural land-management practices may have been partly responsible for an inflated magnitude of low flows at several sites.

  15. All roads lead to Meyrin

    CERN Multimedia

    Communication locale

    2011-01-01

    Tous les chemins mènent à Meyrin - All roads lead to Meyrin From 29 September to 16 October, 2011, come to the Salle Antoine Verchère in Meyrin for Tous les chemins mènent à Meyrin. The celebration will include an exposition as well as a theatrical performance about Meyrin, the first satellite city in Switzerland. With the help of the memories and testimonies from the people of Meyrin, Tous les chemins mènent à Meyrin is putting the collective memories of the commune on display. It is an occasion for everyone, whether you're from near or far, to find out how all the roads lead to Meyrin.  Salle Antoine-Verchère Route de Meyrin 294 – 1217 Meyrin Tram 18 – Stop: Meyrin Village Thursdays / Fridays / Saturdays at 8pm Sundays at 5pm Regular ticket: CHF 15.- Concession ticket (students, chômeurs, AVS, AI): CHF 12.- Children up to 16: CHF 10.- Family ticket: CHF 35.-

  16. From virtuality to reality - Virtual screening in lead discovery and lead optimization: a medicinal chemistry perspective.

    Science.gov (United States)

    Rester, Ulrich

    2008-07-01

    Drug discovery and development is an interdisciplinary, expensive and time-consuming process. Scientific advancements during the past two decades have altered the way pharmaceutical research produces novel bio-active molecules. Advances in computational techniques and hardware solutions have enabled in silico methods, and in particular virtual screening, to speed up modern lead identification and lead optimization. Recent successes have proven the power of combining virtual screening with complementary and synergistic biophysical methods, such as X-ray crystallography, NMR spectroscopy and isothermal titration calorimetry (ITC). This review addresses key issues, challenges and recent improvements of virtual screening methods and strategies. Examples highlighting the impact of an integrated virtual screening and biophysical characterization platform in the lead identification and optimization process are presented and discussed.

  17. Morphological alterations in the dentition of type I diabetes mellitus patients

    Directory of Open Access Journals (Sweden)

    Andamuthu Yamunadevi

    2014-01-01

    Full Text Available Introduction: Type 1 diabetes mellitus (DM is an endocrine disorder that occurs commonly in an age group, where the development of primary and permanent dentition takes place. As altered endocrine functions may affect the shape and size of teeth leading to dental anomalies, this study was conducted to look for the occurrence of any dental anomalies in type I DM patients. Materials and Methods: A diabetic camp was conducted at Alur Chandrashekharappa Memorial Hospital, Davangere, where 30 diabetic patients were examined and the impressions of their maxillary and mandibular arches were recorded. Age and sex matched controls were selected randomly, and similar recordings were done. Results: Type I diabetic patients showed statistically significant (P < 0.001 morphological alterations of total number of cusps, including presence of 6 th cusp in mandibular molars and extra cusps in mandibular premolars. Other alterations such as microdontia, flower shaped mandibular molars, prominent cusp of carabelli, and oblique ridge in maxillary molars were also noted. Severe attrition was found in 11 (36.6% of the diabetic patients, whereas the control group showed attrition only in 2 (6.8% patients. Conclusion: Remarkable morphological alterations do occur in the dentition of type I DM patients.

  18. Genetic alterations in Krebs cycle and its impact on cancer pathogenesis.

    Science.gov (United States)

    Sajnani, Karishma; Islam, Farhadul; Smith, Robert Anthony; Gopalan, Vinod; Lam, Alfred King-Yin

    2017-04-01

    Cancer cells exhibit alterations in many cellular processes, including oxygen sensing and energy metabolism. Glycolysis in non-oxygen condition is the main energy production process in cancer rather than mitochondrial respiration as in benign cells. Genetic and epigenetic alterations of Krebs cycle enzymes favour the shift of cancer cells from oxidative phosphorylation to anaerobic glycolysis. Mutations in genes encoding aconitase, isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydratase, and citrate synthase are noted in many cancers. Abnormalities of Krebs cycle enzymes cause ectopic production of Krebs cycle intermediates (oncometabolites) such as 2-hydroxyglutarate, and citrate. These oncometabolites stabilize hypoxia inducible factor 1 (HIF1), nuclear factor like 2 (Nrf2), inhibit p53 and prolyl hydroxylase 3 (PDH3) activities as well as regulate DNA/histone methylation, which in turn activate cell growth signalling. They also stimulate increased glutaminolysis, glycolysis and production of reactive oxygen species (ROS). Additionally, genetic alterations in Krebs cycle enzymes are involved with increased fatty acid β-oxidations and epithelial mesenchymal transition (EMT) induction. These altered phenomena in cancer could in turn promote carcinogenesis by stimulating cell proliferation and survival. Overall, epigenetic and genetic changes of Krebs cycle enzymes lead to the production of oncometabolite intermediates, which are important driving forces of cancer pathogenesis and progression. Understanding and applying the knowledge of these mechanisms opens new therapeutic options for patients with cancer. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  19. Role of altered coagulation-fibrinolytic system in the pathophysiology of diabetic retinopathy.

    Science.gov (United States)

    Behl, Tapan; Velpandian, Thirumurthy; Kotwani, Anita

    2017-05-01

    The implications of altered coagulation-fibrinolytic system in the pathophysiology of several vascular disorders, such as stroke and myocardial infarction, have been well researched upon and established. However, its role in the progression of diabetic retinopathy has not been explored much. Since a decade, it is known that hyperglycemia is associated with a hypercoagulated state and the various impairments it causes are well acknowledged as independent risk factors for the development of cardiovascular diseases. But recent studies suggest that the hypercoagulative state and diminished fibrinolytic responses might also alter retinal homeostasis and induce several deleterious molecular changes in retinal cells which aggravate the already existing hyperglycemia-induced pathological conditions and thereby lead to the progression of diabetic retinopathy. The major mediators of coagulation-fibrinolytic system whose concentration or activity get altered during hyperglycemia include fibrinogen, antithrombin-III (AT-III), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF). Inhibiting the pathways by which these altered mediators get involved in the pathophysiology of diabetic retinopathy can serve as potential targets for the development of an adjuvant novel alternative therapy for diabetic retinopathy. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Lead in teeth from lead-dosed goats: Microdistribution and relationship to the cumulative lead dose

    International Nuclear Information System (INIS)

    Bellis, David J.; Hetter, Katherine M.; Jones, Joseph; Amarasiriwardena, Dula; Parsons, Patrick J.

    2008-01-01

    Teeth are commonly used as a biomarker of long-term lead exposure. There appear to be few data, however, on the content or distribution of lead in teeth where data on specific lead intake (dose) are also available. This study describes the analysis of a convenience sample of teeth from animals that were dosed with lead for other purposes, i.e., a proficiency testing program for blood lead. Lead concentration of whole teeth obtained from 23 animals, as determined by atomic absorption spectrometry, varied from 0.6 to 80 μg g -1 . Linear regression of whole tooth lead (μg g -1 ) on the cumulative lead dose received by the animal (g) yielded a slope of 1.2, with r 2 =0.647 (p -1 , were found in circumpulpal dentine. Linear regression of circumpulpal lead (μg g -1 ) on cumulative lead dose (g) yielded a slope of 23 with r 2 =0.961 (p=0.0001). The data indicated that whole tooth lead, and especially circumpulpal lead, of dosed goats increased linearly with cumulative lead exposure. These data suggest that circumpulpal dentine is a better biomarker of cumulative lead exposure than is whole tooth lead, at least for lead-dosed goats

  1. The lead industry and lead water pipes "A Modest Campaign".

    Science.gov (United States)

    Rabin, Richard

    2008-09-01

    Lead pipes for carrying drinking water were well recognized as a cause of lead poisoning by the late 1800s in the United States. By the 1920s, many cities and towns were prohibiting or restricting their use. To combat this trend, the lead industry carried out a prolonged and effective campaign to promote the use of lead pipes. Led by the Lead Industries Association (LIA), representatives were sent to speak with plumbers' organizations, local water authorities, architects, and federal officials. The LIA also published numerous articles and books that extolled the advantages of lead over other materials and gave practical advice on the installation and repair of lead pipes. The LIA's activities over several decades therefore contributed to the present-day public health and economic cost of lead water pipes.

  2. Glycogene expression alterations associated with pancreatic cancer epithelial-mesenchymal transition in complementary model systems.

    Directory of Open Access Journals (Sweden)

    Kevin A Maupin

    2010-09-01

    Full Text Available The ability to selectively detect and target cancer cells that have undergone an epithelial-mesenchymal transition (EMT may lead to improved methods to treat cancers such as pancreatic cancer. The remodeling of cellular glycosylation previously has been associated with cell differentiation and may represent a valuable class of molecular targets for EMT.As a first step toward investigating the nature of glycosylation alterations in EMT, we characterized the expression of glycan-related genes in three in-vitro model systems that each represented a complementary aspect of pancreatic cancer EMT. These models included: 1 TGFβ-induced EMT, which provided a look at the active transition between states; 2 a panel of 22 pancreatic cancer cell lines, which represented terminal differentiation states of either epithelial-like or mesenchymal-like; and 3 actively-migrating and stationary cells, which provided a look at the mechanism of migration. We analyzed expression data from a list of 587 genes involved in glycosylation (biosynthesis, sugar transport, glycan-binding, etc. or EMT. Glycogenes were altered at a higher prevalence than all other genes in the first two models (p<0.05 and <0.005, respectively but not in the migration model. Several functional themes were shared between the induced-EMT model and the cell line panel, including alterations to matrix components and proteoglycans, the sulfation of glycosaminoglycans; mannose receptor family members; initiation of O-glycosylation; and certain forms of sialylation. Protein-level changes were confirmed by Western blot for the mannose receptor MRC2 and the O-glycosylation enzyme GALNT3, and cell-surface sulfation changes were confirmed using Alcian Blue staining.Alterations to glycogenes are a major component of cancer EMT and are characterized by changes to matrix components, the sulfation of GAGs, mannose receptors, O-glycosylation, and specific sialylated structures. These results provide leads for

  3. Chromite alteration processes within Vourinos ophiolite

    Science.gov (United States)

    Grieco, Giovanni; Merlini, Anna

    2012-09-01

    The renewed interest in chromite ore deposits is directly related to the increase in Cr price ruled by international market trends. Chromite, an accessory mineral in peridotites, is considered to be a petrogenetic indicator because its composition reflects the degree of partial melting that the mantle experienced while producing the chromium spinel-bearing rock (Burkhard in Geochim Cosmochim Acta 57:1297-1306, 1993). However, the understanding of chromite alteration and metamorphic modification is still controversial (e.g. Evans and Frost in Geochim Cosmochim Acta 39:959-972, 1975; Burkhard in Geochim Cosmochim Acta 57:1297-1306, 1993; Oze et al. in Am J Sci 304:67-101, 2004). Metamorphic alteration leads to major changes in chromite chemistry and to the growth of secondary phases such as ferritchromite and chlorite. In this study, we investigate the Vourinos complex chromitites (from the mines of Rizo, Aetoraches, Xerolivado and Potamia) with respect to textural and chemical analyses in order to highlight the most important trend of alteration related to chromite transformation. The present study has been partially funded by the Aliakmon project in collaboration between the Public Power Corporation of Greece and Institute of Geology and Mineral Exploration of Kozani.

  4. Lead pollution sources and Impacts

    International Nuclear Information System (INIS)

    El-Haggar, S.M.; Saad, S.G.; Saleh, S.K.; El-Kady, M.A.

    1996-01-01

    Despite the medical awareness of lead toxicity, and despite legislation designed to reduce environmental contamination, lead is one of the most widely used heavy metals. Significant human exposure occurs from automobile exhaust fumes, cigarette smoking, lead-based paints and plumbing systems lead spread in the environment can take place in several ways, the most important of which is through the lead compounds released in automobile exhaust as a direct result of the addition of tetraethyl or tetraethyl lead to gasoline as octane boosting agents. Of special is the effect of lead pollution on children, which affects their behavioral and educational attributes considerably. The major channel through through which lead is absorbed is through inhalation of lead compounds in the atmosphere. Lead is a heavy metal characterized its malleability, ductility and poor conduction of electricity. So, it has a wide range of applications ranging from battery manufacturing to glazing ceramics. It is rarely found free in nature but is present in several minerals and compounds. The aim of this paper is to discuss natural and anthropogenic sources of lead together with its distribution and trends with emphasis on egypt. The effects of lead pollution on human health, vegetation and welfare are also presented. It could be concluded that, the excessive release of lead into the environment, especially through the atmosphere, can produce many detrimental and sometimes fatal effects on human, agriculture and zoological life. Besides, it is very plain that there is a serious problem of pollution lead in egypt and specially in cairo. 7 figs

  5. Environmental lead pollution and contamination in food around ...

    African Journals Online (AJOL)

    Exposure to lead (Pb) through food, water, or contaminated air has adverse health impacts that are particularly severe in children. Many countries have outlawed the use of leaded petrol, and enacted policies and regulations limiting lead pollution, and lead levels in foods. However, African countries, including Kenya, have ...

  6. Lead in a residential environment in Jamaica.

    Science.gov (United States)

    Anglin-Brown, B; Armour-Brown, A; Lalor, G C; Preston, J; Vutchkov, M K

    1996-09-01

    The background levels of lead in Jamaica in soils and sediments, estimated at 37 mg kg(-1), are relatively high compared with world averages. Several areas have values in excess of this due to mineralisation and pollution. One such is the residential Hope Flats/Kintyre area in which levels of lead up to 2.5% are found in the soils and up to 8 μg kg(-1) in the water of the nearby Hope River. The blood lead levels of a sample of children were in the range 5.7-57 μg dl(-1). The high lead levels suggest a potential health risk, particularly for the children. This can be minimised by programmes which include community education, case management and abatement to reduce the lead exposure.

  7. Lead Coolant Test Facility Development Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Paul A. Demkowicz

    2005-06-01

    A workshop was held at the Idaho National Laboratory on May 25, 2005, to discuss the development of a next generation lead or lead-alloy coolant test facility. Attendees included representatives from the Generation IV lead-cooled fast reactor (LFR) program, Advanced Fuel Cycle Initiative, and several universities. Several participants gave presentations on coolant technology, existing experimental facilities for lead and lead-alloy research, the current LFR design concept, and a design by Argonne National Laboratory for an integral heavy liquid metal test facility. Discussions were focused on the critical research and development requirements for deployment of an LFR demonstration test reactor, the experimental scope of the proposed coolant test facility, a review of the Argonne National Laboratory test facility design, and a brief assessment of the necessary path forward and schedule for the initial stages of this development project. This report provides a summary of the presentations and roundtable discussions.

  8. Do leading indicators lead peaks more than troughs?

    NARCIS (Netherlands)

    R. Paap (Richard); R. Segers (René); D.J.C. van Dijk (Dick)

    2007-01-01

    textabstractWe develop a formal statistical approach to investigate the possibility that leading indicator variables have different lead times at business cycle peaks and troughs. For this purpose, we propose a novel Markov switching vector autoregressive model, where economic growth and leading

  9. Lead Contamination and Microbial Lead Tolerance in Soils at Major ...

    African Journals Online (AJOL)

    Devika

    ABSTRACT: Lead pollution and lead tolerance levels of microbes in soil at major road junctions in Benin. City were investigated. Results revealed that distance from the road junctions affected the concentrations of lead in soil, as well as the microbial population density and types of microbes present in the soil. The highest ...

  10. Blood lead level as biomarker of environmental lead pollution in ...

    African Journals Online (AJOL)

    The ideal blood lead level is now considered to be zero. Lead pollution of the study area has serious consequences on aquatic fauna and humans who consume such contaminated fish. It is therefore recommended that human and animal health surveillance and environmental monitoring of lead should be initiated.

  11. Lead Contamination and Microbial Lead Tolerance in Soils at Major ...

    African Journals Online (AJOL)

    Lead pollution and lead tolerance levels of microbes in soil at major road junctions in Benin City were investigated. Results revealed that distance from the road junctions affected the concentrations of lead in soil, as well as the microbial population density and types of microbes present in the soil. The highest concentrations ...

  12. Leaded gasoline - an environmental problem

    International Nuclear Information System (INIS)

    Petrushevska, Ljubica

    2001-01-01

    In the European countries it is a clear trend towards the increasing consumption of unleaded gasolines. Driving force of this trend is, on the one hand the high toxicity of lead compounds and on the other, the necessity of purification of exhaust gases by catalytic converters, for which the lead represent a catalyst poison. In Macedonia, the limit lead content in the leaded gasolines is relatively high (0,6 g/l), as well as the consumption of the leaded gasolines. Rapid and complete transition to unleaded gasolines can be realized by the concept of step by step reduction of lead in our gasolines. (Original)

  13. Thymoquinone ameliorates lead-induced suppression of the ...

    African Journals Online (AJOL)

    Objective: Alteration of the antioxidant status in the kidneys may be related to lead (Pb) intoxication. The present study aimed to investigate the possible beneficial effect of thymoquinone (TQ), the major active ingredient of the volatile oil of Nigella sativa seeds, on Pb-induced renal antioxidant defense system impairment.

  14. Including gauge corrections to thermal leptogenesis

    International Nuclear Information System (INIS)

    Huetig, Janine

    2013-01-01

    This thesis provides the first approach of a systematic inclusion of gauge corrections to leading order to the ansatz of thermal leptogenesis. We have derived a complete expression for the integrated lepton number matrix including all resummations needed. For this purpose, a new class of diagram has been invented, namely the cylindrical diagram, which allows diverse investigations into the topic of leptogenesis such as the case of resonant leptogenesis. After a brief introduction of the topic of the baryon asymmetry in the universe and a discussion of its most promising solutions as well as their advantages and disadvantages, we have presented our framework of thermal leptogenesis. An effective model was described as well as the associated Feynman rules. The basis for using nonequilibrium quantum field theory has been built in chapter 3. At first, the main definitions have been presented for equilibrium thermal field theory, afterwards we have discussed the Kadanoff-Baym equations for systems out of equilibrium using the example of the Majorana neutrino. The equations have also been solved in the context of leptogenesis in chapter 4. Since gauge corrections play a crucial role throughout this thesis, we have also repeated the naive ansatz by replacing the free equilibrium propagator by propagators including thermal damping rates due to the Standard Model damping widths for lepton and Higgs fields. It is shown that this leads to a comparable result to the solutions of the Boltzmann equations for thermal leptogenesis. Thus it becomes obvious that Standard Model corrections are not negligible for thermal leptogenesis and therefore need to be included systematically from first principles. In order to achieve this we have started discussing the calculation of ladder rung diagrams for Majorana neutrinos using the HTL and the CTL approach in chapter 5. All gauge corrections are included in this framework and thus it has become the basis for the following considerations

  15. Leading by feel.

    Science.gov (United States)

    2004-01-01

    Like it or not, leaders need to manage the mood of their organizations. The most gifted leaders accomplish that by using a mysterious blend of psychological abilities known as emotional intelligence. They are self-aware and empathetic. They can read and regulate their own emotions while intuitively grasping how others feel and gauging their organization's emotional state. But where does emotional intelligence come from, and how do leaders learn to use it? In this article, 18 leaders and scholars (including business executives, leadership researchers, psychologists, an autism expert, and a symphony conductor) explore the nature and management of emotional intelligence--its sources, uses, and abuses. Their responses varied, but some common themes emerged: the importance of consciously--and conscientiously--honing one's skills, the double-edged nature of self-awareness, and the danger of letting any one emotional intelligence skill dominate. Among their observations: Psychology professor John Mayer, who co-developed the concept of emotional intelligence, warns managers not to be confused by popular definitions of the term, which suggest that if you have a certain set of personality traits then you automatically possess emotional intelligence. Neuropsychologist Elkhonon Goldberg agrees with professors Daniel Goleman and Robert Goffee that emotional intelligence can be learned--but only by people who already show an aptitude for it. Cult expert Janja Lalich points out that leaders can use their emotional intelligence skills for ill in the same way they can for good. "Sometimes the only difference is [the leader's] intent," she says. And business leaders Carol Bartz, William George, Sidney Harman, and Andrea jung (of Autodesk, Medtronic, Harman International, and Avon respectively) describe situations in which emotional intelligence traits such as self-awareness and empathy have helped them and their companies perform at a higher level.

  16. Genetic alteration in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Chul; Kang, Tae Woong; Lee, Jin Oh [Korea Cancer Center Hospital of Korea Atomic Energy Research Institute, Seoul (Korea, Republic of)

    1994-12-01

    Cancer of stomach, colon and liver are a group of the most common cancer in Korea. However, results with current therapeutic modalities are still unsatisfactory. The intensive efforts have been made to understand basic pathogenesis and to find better therapeutic tools for the treatment of this miserable disease. We studied the alteration of tumor suppressor genes and oncogenes in hepatocellular carcinoma in Korea. We found that alteration of Rb gene, APC were 33 %, 13 % respectively. But alterations of oncogenes such as myc, ras and mdm2 were rarely found. Our results suggests that HBV may act as oncogenic role in hepatocarcinogenesis instead of oncogenes. 6 figs, 2 tabs. (Author).

  17. Renovate Right: Prevent Lead Poisoning in Children

    Centers for Disease Control (CDC) Podcasts

    2008-10-02

    In this podcast, Dr. Maria Doa, Director of the Environmental Protection Agency's (EPA) National Program Chemicals Division, discusses EPA's new rule for renovations, repairs, and painting activities. The new rule includes information on lead-safe work practices when conducting renovations, repairs, and painting in pre-1978 homes and schools to prevent the spread of lead dust.  Created: 10/2/2008 by National Center for Environmental Health (NCEH).   Date Released: 10/2/2008.

  18. Primer on lead-acid storage batteries

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    This handbook was developed to help DOE facility contractors prevent accidents caused during operation and maintenance of lead-acid storage batteries. Major types of lead-acid storage batteries are discussed as well as their operation, application, selection, maintenance, and disposal (storage, transportation, as well). Safety hazards and precautions are discussed in the section on battery maintenance. References to industry standards are included for selection, maintenance, and disposal.

  19. Plutonium alteration phases from lanthanide borosilicate glass

    International Nuclear Information System (INIS)

    Fortner, J.A.; Mertz, C.J.; Chamberlain, D.C.; Bates, J.K.

    1997-01-01

    A prototype lanthanide borosilicate (LaBS) glass containing 10 mass % plutonium was reacted with water vapor at 200 C for periods of 14 to 56 days. These tests, while not designed to replicate specific conditions that may be found in a potential geologic repository (e.g., Yucca Mountain), have been shown to accelerate alteration phase formation. The surfaces of the glass samples, along with alteration phases, were examined with a transmission electron microscope (TEM). Tests of 14 days produced macroscopic (∼ 20 microm) crystallites of a plutonium-lanthanide silicate. An extensive alteration layer was found on the glass surface containing amorphous aluminosilicate layered with bands of a cryptocrystalline plutonium silicate. After 56 days of testing, additional alteration phases were formed, including a strontium lanthanide oxide phase. One of the options for disposal of surplus plutonium, particularly for impure residues that may be unfit for production of MOX fuel, is vitrification followed by geologic disposal. Since geologic disposal requires a passive system to isolate the radiotoxic elements from the biosphere, it is important to understand the possible corrosion mechanisms of the waste form

  20. Ocean acidification alters fish–jellyfish symbiosis

    Science.gov (United States)

    Nagelkerken, Ivan; Pitt, Kylie A.; Rutte, Melchior D.; Geertsma, Robbert C.

    2016-01-01

    Symbiotic relationships are common in nature, and are important for individual fitness and sustaining species populations. Global change is rapidly altering environmental conditions, but, with the exception of coral–microalgae interactions, we know little of how this will affect symbiotic relationships. We here test how the effects of ocean acidification, from rising anthropogenic CO2 emissions, may alter symbiotic interactions between juvenile fish and their jellyfish hosts. Fishes treated with elevated seawater CO2 concentrations, as forecast for the end of the century on a business-as-usual greenhouse gas emission scenario, were negatively affected in their behaviour. The total time that fish (yellowtail scad) spent close to their jellyfish host in a choice arena where they could see and smell their host was approximately three times shorter under future compared with ambient CO2 conditions. Likewise, the mean number of attempts to associate with jellyfish was almost three times lower in CO2-treated compared with control fish, while only 63% (high CO2) versus 86% (control) of all individuals tested initiated an association at all. By contrast, none of three fish species tested were attracted solely to jellyfish olfactory cues under present-day CO2 conditions, suggesting that the altered fish–jellyfish association is not driven by negative effects of ocean acidification on olfaction. Because shelter is not widely available in the open water column and larvae of many (and often commercially important) pelagic species associate with jellyfish for protection against predators, modification of the fish–jellyfish symbiosis might lead to higher mortality and alter species population dynamics, and potentially have flow-on effects for their fisheries. PMID:27358374

  1. Pb Neurotoxicity: Neuropsychological Effects of Lead Toxicity

    Directory of Open Access Journals (Sweden)

    Lisa H. Mason

    2014-01-01

    Full Text Available Neurotoxicity is a term used to describe neurophysiological changes caused by exposure to toxic agents. Such exposure can result in neurocognitive symptoms and/or psychiatric disturbances. Common toxic agents include heavy metals, drugs, organophosphates, bacterial, and animal neurotoxins. Among heavy metal exposures, lead exposure is one of the most common exposures that can lead to significant neuropsychological and functional decline in humans. In this review, neurotoxic lead exposure's pathophysiology, etiology, and epidemiology are explored. In addition, commonly associated neuropsychological difficulties in intelligence, memory, executive functioning, attention, processing speed, language, visuospatial skills, motor skills, and affect/mood are explored.

  2. Cavitation on hydrofoils with sinusoidal leading edge

    Science.gov (United States)

    Johari, H.

    2015-12-01

    Cavitation characteristics of hydrofoils with sinusoidal leading edge were examined experimentally at a Reynolds number of 7.2 × 105. The hydrofoils had an underlying NACA 634-021 profile and an aspect ratio of 4.3. The sinusoidal leading edge geometries included three amplitudes of 2.5%, 5%, and 12% and two wavelengths of 25% and 50% of the mean chord length. Results revealed that cavitation on the leading edge-modified hydrofoils existed in pockets behind the troughs whereas the baseline hydrofoil produced cavitation along its entire span. Moreover, cavitation on the modified hydrofoils appeared at consistently lower angles of attack than on the baseline hydrofoil.

  3. Secondary lead production in Malaysia

    Science.gov (United States)

    Phillips, M. J.; Lim, S. S.

    The increase in the number of vehicles and, subsequently, the volume of batteries made by manufacturers in Malaysia have seen a dramatic rise in lead demand over the last five years. Without any lead mines, the only source of lead in Malaysia has been from the recycling of lead/acid batteries. Metal Reclamation (Industries) has commenced the design of a new and advanced secondary lead plant at West Port, Malaysia to meet the increasing demand for lead and the increasingly stringent environmental regulations. The plant is designed to produce up to 75 000 t of lead and lead alloys per year. The plant will also produce, as by-products: polypropylene chips, wallboard-grade gypsum, non-leachable slag for use in construction. A discussion of the process and the products from the new secondary smelter is outlined.

  4. Safety and Health Topics: Lead

    Science.gov (United States)

    ... enters the body primarily through inhalation and ingestion. Today, adults are mainly exposed to lead by breathing ... can provide a snapshot of industry sectors and business subcategories where lead air concentrations have been found. ...

  5. Vitamin D alteration associated with obesity and bariatric surgery.

    Science.gov (United States)

    Lespessailles, Eric; Toumi, Hechmi

    2017-05-01

    Obesity and severe obesity constitute growing serious health problems reaching epidemic proportion in most countries. Interactions and relationships between obesity and bone tissue and its metabolism are complex but are more and more studied and recognized. Obesity is associated with an altered hormonal profile including particularly bone-regulating hormones like vitamin D. Bariatric surgery procedures, thanks to their effectiveness to achieve therapeutic endpoints for comorbidities associated with obesity, have had an increasing success. However, these surgeries by producing mechanical restriction and or malabsorption syndrome lead to nutritional deficiencies including vitamin D. In this review, we aim to (1) discuss the nutritional deficiency of vitamin D in the obese, (2) to summarize the different surgical options in bariatric surgery and to present the evidence concerning these procedures and their associated profile in vitamin D post-operative insufficiency, (3) to present the different recommendations in clinical practice to prevent or treat vitamin D deficiencies or insufficiencies in patients treated by bariatric surgery and finally to introduce emerging assumptions on the relationship between vitamin D, microbiota composition and circulating bile acids. Impact statement Obesity and severe obesity constitute growing serious health problems reaching epidemic proportion in most countries with a prevalence increasing from 6.4 in 1975 to 14.9% in 2014. This present review summarizes currently available data on vitamin D deficiencies in the obese population before and after bariatric surgery. The important evidence emerging from our evaluation confirms that obese patients are at risk of multiple nutritional deficiencies, especially vitamin D deficiency, before bariatric surgery. Our survey confirms that the precise role of the gut microbiome and its associated changes on the vitamin D metabolism after the different bariatric surgery procedures has not yet been

  6. Cigarette smoke exposure-associated alterations to noncoding RNA

    Directory of Open Access Journals (Sweden)

    Matthew Alan Maccani

    2012-04-01

    Full Text Available Environmental exposures vary by timing, severity, and frequency and may have a number of deleterious effects throughout the life course. The period of in utero development, for example, is one of the most crucial stages of development during which adverse environmental exposures can both alter the growth and development of the fetus as well as lead to aberrant fetal programming, increasing disease risk. During fetal development and beyond, the plethora of exposures, including nutrients, drugs, stress, and trauma, influence health, development, and survival. Recent research in environmental epigenetics has investigated the roles of environmental exposures in influencing epigenetic modes of gene regulation during pregnancy and at various stages of life. Many relatively common environmental exposures, such as cigarette smoking, alcohol consumption, and drug use, may have consequences for the expression and function of noncoding RNA (ncRNA, important post-transcriptional regulators of gene expression. A number of ncRNA have been discovered, including microRNA (miRNA, Piwi-interacting RNA (piRNA, and long noncoding RNA (long ncRNA. The best-characterized species of ncRNA are miRNA, the mature forms of which are ~22 nucleotides in length and capable of post-transcriptionally regulating target mRNA utilizing mechanisms based largely on the degree of complementarity between miRNA and target mRNA. Because miRNA can still negatively regulate gene expression when imperfectly base-paired with a target mRNA, a single miRNA can have a large number of potential mRNA targets and can regulate many different biological processes critical for health and development. The following review analyzes the current literature detailing links between cigarette smoke exposure and aberrant expression and function of noncoding RNA, assesses how such alterations may have consequences throughout the life course, and proposes future directions for this intriguing field of

  7. Genotoxic effects of occupational exposure to lead and influence of polymorphisms in genes involved in lead toxicokinetics and in DNA repair.

    Science.gov (United States)

    García-Lestón, Julia; Roma-Torres, Joana; Vilares, Maria; Pinto, Rui; Prista, João; Teixeira, João Paulo; Mayan, Olga; Conde, João; Pingarilho, Marta; Gaspar, Jorge Francisco; Pásaro, Eduardo; Méndez, Josefina; Laffon, Blanca

    2012-08-01

    Lead is still widely used in many industrial processes and is very persistent in the environment. Although toxic effects caused by occupational exposure to lead have been extensively studied, there are still conflicting results regarding its genotoxicity. In a previous pilot study we observed some genotoxic effects in a population of lead exposed workers. Thus, we extended our study analysing a larger population, increasing the number of genotoxicity endpoints, and including a set of 20 genetic polymorphisms related to lead toxicokinetics and DNA repair as susceptibility biomarkers. Our population comprised 148 workers from two Portuguese factories and 107 controls. The parameters analysed were: blood lead levels (BLL) and δ-aminolevulinic acid dehydratase (ALAD) activity as exposure biomarkers, and T-cell receptor (TCR) mutation assay, micronucleus (MN) test, comet assay and OGG1-modified comet assay as genotoxicity biomarkers. Lead exposed workers showed markedly higher BLL and lower ALAD activity than the controls, and significant increases of TCR mutation frequency (TCR-Mf), MN rate and DNA damage. Oxidative damage did not experience any significant alteration in the exposed population. Besides, significant influence was observed for VDR rs1544410 polymorphism on BLL; APE1 rs1130409 and LIG4 rs1805388 polymorphisms on TCR-Mf; MUTYH rs3219489, XRCC4 rs28360135 and LIG4 rs1805388 polymorphisms on comet assay parameter; and OGG1 rs1052133 and XRCC4 rs28360135 polymorphisms on oxidative damage. Our results showed genotoxic effects related to occupational lead exposure to levels under the Portuguese regulation limit of 70 μg/dl. Moreover, a significant influence of polymorphisms in genes involved in DNA repair on genotoxicity biomarkers was observed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Environmental Lead and Children's Health.

    Science.gov (United States)

    Lewis, Marie

    This paper discusses the threat to children's health posed by environmental exposure to lead, focusing on public policy issues surrounding lead exposure in New South Wales (NSW), Australia. In Australia, the current blood lead level at which there is a health concern is at or above 25 micrograms per deciliter (ug/dl) of blood for infants and…

  9. 75 FR 43942 - Children's Products Containing Lead; Technological Feasibility of 100 ppm for Lead Content...

    Science.gov (United States)

    2010-07-27

    ... children's products. The reduction can be for a product or product category. This notice requests comment..., including metals, plastics, glass, or recycled materials that are at or below the 100 ppm lead content limit... any, the use of materials that are compliant with the 100 ppm lead content limit, has on the...

  10. Phosphofructo-1-kinase deficiency leads to a severe cardiac and hematological disorder in addition to skeletal muscle glycogenosis.

    Directory of Open Access Journals (Sweden)

    Miguel García

    2009-08-01

    Full Text Available Mutations in the gene for muscle phosphofructo-1-kinase (PFKM, a key regulatory enzyme of glycolysis, cause Type VII glycogen storage disease (GSDVII. Clinical manifestations of the disease span from the severe infantile form, leading to death during childhood, to the classical form, which presents mainly with exercise intolerance. PFKM deficiency is considered as a skeletal muscle glycogenosis, but the relative contribution of altered glucose metabolism in other tissues to the pathogenesis of the disease is not fully understood. To elucidate this issue, we have generated mice deficient for PFKM (Pfkm(-/-. Here, we show that Pfkm(-/- mice had high lethality around weaning and reduced lifespan, because of the metabolic alterations. In skeletal muscle, including respiratory muscles, the lack of PFK activity blocked glycolysis and resulted in considerable glycogen storage and low ATP content. Although erythrocytes of Pfkm(-/- mice preserved 50% of PFK activity, they showed strong reduction of 2,3-biphosphoglycerate concentrations and hemolysis, which was associated with compensatory reticulocytosis and splenomegaly. As a consequence of these haematological alterations, and of reduced PFK activity in the heart, Pfkm(-/- mice developed cardiac hypertrophy with age. Taken together, these alterations resulted in muscle hypoxia and hypervascularization, impaired oxidative metabolism, fiber necrosis, and exercise intolerance. These results indicate that, in GSDVII, marked alterations in muscle bioenergetics and erythrocyte metabolism interact to produce a complex systemic disorder. Therefore, GSDVII is not simply a muscle glycogenosis, and Pfkm(-/- mice constitute a unique model of GSDVII which may be useful for the design and assessment of new therapies.

  11. Lead levels in Maryland construction workers.

    Science.gov (United States)

    Sokas, R K; Simmens, S; Sophar, K; Welch, L S; Liziewski, T

    1997-02-01

    A cross-sectional study of unionized construction workers not currently known to be performing lead work was conducted. Participants completed an interviewer-administered questionnaire obtaining information about demographics, work history, other possible sources of lead exposure and health status (including hypertension, noise-induced hearing loss and renal disease). Blood was then obtained via venipuncture for whole blood lead level, hematocrit and free erythrocyte protoporphyrin determination. Two hundred and sixty-four Maryland construction workers had median whole blood lead determinations of 7 micrograms/dl and mean values of 8.0 micrograms/dl, with a skewed distribution ranging from 2 to 30 micrograms/dl. None were currently engaged in known lead work. Blood lead levels were significantly higher for the 124 who had 'ever' worked in demolition (8.8 micrograms/dl vs. 7.2 micrograms/dl, p = .004), and for the 79 who had ever burned paint and metal and welded on outdoor structures compared to the 48 who had done none of these activities (8.6 micrograms/dl vs. 6.8 micrograms/dl, p = .01). The 58 workers who had ever had workplace lead monitoring performed had higher lead levels (9.7 vs. 7.5 micrograms/dl, p = .003). Blood lead levels increased with age, and cigarette smoking. African Americans (N = 68) had higher lead levels (9.1 vs. 7.5 micrograms/dl, p = .01). There were only two women in the study, one with a lead level of 21 micrograms/dl and one, 7 micrograms/dl. Blood lead levels did not predict either systolic or diastolic blood pressure in this population. However, there was a significant interaction between race and lead as predictors of blood pressure, with blacks demonstrating a trend-significant correlation, and whites showing a nonsignificant but negative association. Demolition and hotwork on outdoor structures are known to cause acute episodes of lead poisoning. They also appear to cause slight but persistent increases in blood lead levels. Future

  12. Presence of lead in opium.

    Science.gov (United States)

    Aghaee-Afshar, Mahmoud; Khazaeli, Payam; Behnam, Behzad; Rezazadehkermani, Mohammad; Ashraf-Ganjooei, Narges

    2008-09-01

    Opium addiction is a common form of addiction in Middle East countries such as Iran. Recently several reports suggested some kinds of pathologic findings such as abdominal pain, nephropathy, and anemia in opium addict patients. Such pathologic findings suggest lead poisoning in the patients. In this study, the concentration of lead in 10 opium samples was evaluated. The mean concentration of lead in the opium samples was 1.88 ppm. This may explain some of the pathologic findings found in addict patients. The authors would suggest further investigations to evaluate the lead concentration in opium addicts' sera and also routine screening for lead poisoning in opium addict patients.

  13. Neurophysiological effects of lead exposure

    Energy Technology Data Exchange (ETDEWEB)

    Rosen, I.; Wildt, K.; Gullberg, B.; Berlin, M.

    1983-10-01

    A series of neurophysiological variables was measured for men occupationally exposed to lead. The results were related to the degree of lead exposure and to the concentrations of lead and zinc protoporphyrin in blood. A small but significant correlation was observed between lead exposure and motor and sensory conduction velocities in the lower limbs, the conduction velocities of slow motor fibers in the upper limbs, and also sensory nerve action potentials. It is suggested that a neurophysiological examination should be considered in the surveillance of the health of lead workers.

  14. Blood lead and lead-210 origins in residents of Toulouse

    International Nuclear Information System (INIS)

    Servant, J.; Delapart, M.

    1981-01-01

    Blood lead and lead-210 analyses were performed on blood samples from non-smoking residents of Toulouse (city of 400,000 inhabitants). Simultaneous surface soil lead content determinations were carried out by the same procedure on rural zone samples of southwestern France. The observed isotopic ratios were compared in order to evaluate food chain contamination. For an average of 19.7 +- 5.8 μg 100 cc -1 of lead in blood, atmospheric contamination amounts to 20%, estimated as follows: 6% from direct inhalation and 14% from dry deposits on vegetation absorbed as food. The natural levels carried over by the food chain reach 14.9 μg 100 cc -1 and have a 210 Pb/Pb concentration ratio of 0.055 dpmμg -1 . These results lead to a maximum value of 15 μg 100 cc -1 for natural lead in human blood according to the ICRP model. (author)

  15. Lead

    Science.gov (United States)

    ... Center for Environmental Health , Division of Emergency and Environmental Health Services Email Recommend Tweet YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs Funding LEGAL Policies Privacy FOIA No Fear Act OIG 1600 Clifton ...

  16. Pyrogenic organic matter can alter microbial communication

    Science.gov (United States)

    Masiello, Caroline; Gao, Xiaodong; Cheng, Hsiao-Ying; Silberg, Jonathan

    2016-04-01

    Soil microbes communicate with each other to manage a large range of processes that occur more efficiently when microbes are able to act simultaneously. This coordination occurs through the continuous production of signaling compounds that are easily diffused into and out of cells. As the number of microbes in a localized environment increases, the internal cellular concentration of these signaling compounds increases, and when a threshold concentration is reached, gene expression shifts, leading to altered (and coordinated) microbial behaviors. Many of these coordinated behaviors have biogeochemically important outcomes. For example, methanogenesis, denitrification, biofilm formation, and the development of plant-rhizobial symbioses are all regulated by a simple class of cell-cell signaling molecules known as acyl homoserine lactones (AHLs). Pyrogenic organic matter in soils can act to disrupt microbial communication through multiple pathways. In the case of AHLs, charcoal's very high surface area can sorb these signaling compounds, preventing microbes from detecting each others' presence (Masiello et al., 2014). In addition, the lactone ring in AHLs is vulnerable to pH increases accompanying PyOM inputs, with soil pH values higher than 7-8 leading to ring opening and compound destabilization. Different microbes use different classes of signaling compounds, and not all microbial signaling compounds are pH-vulnerable. This implies that PyOM-driven pH increases may trigger differential outcomes for Gram negative bacteria vs fungi, for example. A charcoal-driven reduction in microbes' ability to detect cell-cell communication compounds may lead to a shift in the ability of microbes to participate in key steps of C and N cycling. For example, an increase in an archaeon-specific AHL has been shown to lead to a cascade of metabolic processes that eventually results in the upregulation of CH4 production (Zhang et al., 2012). Alterations in similar AHL compounds leads to

  17. Modeling of Blood Lead Levels in Astronauts Exposed to Lead from Microgravity-Accelerated Bone Loss

    Science.gov (United States)

    Garcia, H.; James, J.; Tsuji, J.

    2014-01-01

    Human exposure to lead has been associated with toxicity to multiple organ systems. Studies of various population groups with relatively low blood lead concentrations (bones, the adverse effects of lead correlate with the concentration of lead in the blood better than with that in the bones. NASA has found that prolonged exposure to microgravity during spaceflight results in a significant loss of bone minerals, the extent of which varies from individual to individual and from bone to bone, but generally averages about 0.5% per month. During such bone loss, lead that had been stored in bones would be released along with calcium. The effects on the concentration of lead in the blood (PbB) of various concentrations of lead in drinking water (PbW) and of lead released from bones due to accelerated osteoporosis in microgravity, as well as changes in exposure to environmental lead before, during, and after spaceflight were evaluated using a physiologically based pharmacokinetic (PBPK) model that incorporated exposure to environmental lead both on earth and in flight and included temporarily increased rates of osteoporosis during spaceflight.

  18. High glucose alters retinal astrocytes phenotype through increased production of inflammatory cytokines and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Eui Seok Shin

    Full Text Available Astrocytes are macroglial cells that have a crucial role in development of the retinal vasculature and maintenance of the blood-retina-barrier (BRB. Diabetes affects the physiology and function of retinal vascular cells including astrocytes (AC leading to breakdown of BRB. However, the detailed cellular mechanisms leading to retinal AC dysfunction under high glucose conditions remain unclear. Here we show that high glucose conditions did not induce the apoptosis of retinal AC, but instead increased their rate of DNA synthesis and adhesion to extracellular matrix proteins. These alterations were associated with changes in intracellular signaling pathways involved in cell survival, migration and proliferation. High glucose conditions also affected the expression of inflammatory cytokines in retinal AC, activated NF-κB, and prevented their network formation on Matrigel. In addition, we showed that the attenuation of retinal AC migration under high glucose conditions, and capillary morphogenesis of retinal endothelial cells on Matrigel, was mediated through increased oxidative stress. Antioxidant proteins including heme oxygenase-1 and peroxiredoxin-2 levels were also increased in retinal AC under high glucose conditions through nuclear localization of transcription factor nuclear factor-erythroid 2-related factor-2. Together our results demonstrated that high glucose conditions alter the function of retinal AC by increased production of inflammatory cytokines and oxidative stress with significant impact on their proliferation, adhesion, and migration.

  19. Taking the Lead : Gender, Social Context and Preference to Lead

    NARCIS (Netherlands)

    Hong, A.P.C.I.; Schaafsma, J.; van der Wijst, P.J.

    2014-01-01

    Previous research has demonstrated that women tend to emerge as leaders less often than men. In the present study, we examined to what extent women's and men's preference to lead is influenced by social context. It was hypothesized that women have a less strong preference to lead than men in a

  20. Genetic susceptibility to lead poisoning.

    OpenAIRE

    Onalaja, A O; Claudio, L

    2000-01-01

    Major strides have been taken in the regulation of lead intoxication in the general population, but studies using genetic markers of susceptibility to environmental toxicants raise the question of whether genes can make certain individuals more vulnerable to environmental toxins such as lead. At least three polymorphic genes have been identified that potentially can influence the bioaccumulation and toxicokinetics of lead in humans. The first gene to be discussed in this review is the gene co...

  1. Safe leads and lead changes in competitive team sports

    Science.gov (United States)

    Clauset, A.; Kogan, M.; Redner, S.

    2015-06-01

    We investigate the time evolution of lead changes within individual games of competitive team sports. Exploiting ideas from the theory of random walks, the number of lead changes within a single game follows a Gaussian distribution. We show that the probability that the last lead change and the time of the largest lead size are governed by the same arcsine law, a bimodal distribution that diverges at the start and at the end of the game. We also determine the probability that a given lead is "safe" as a function of its size L and game time t . Our predictions generally agree with comprehensive data on more than 1.25 million scoring events in roughly 40 000 games across four professional or semiprofessional team sports, and are more accurate than popular heuristics currently used in sports analytics.

  2. Proteinuria of industrial lead intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Vacca, C.V.; Hines, J.D.; Hall, P.W. III

    1986-12-01

    Studies of protein excretion were undertaken in seven males, aged 35-42 years, who had more than 5 years exposure to industrial lead and had clinically established Pb intoxication. Heavy metal intoxication with Cd and Hg causes proximal tubular abnormalities, i.e., aminoaciduria, glycosuria, phosphaturia. Similar abnormalities occur in Pb intoxication except that the nature of the proteinuria remains controversial. Studies of urinary proteins included 24-hr urine protein excretion, dextran gel separations, sodium dodecyl sulfate-polyacryl-amide gel electrophoresis (SDS-PAGE), and ..beta../sub 2/ microglobulin (B/sub 2/M) measurements. Creatinine clearances, and serum B/sub 2/M concentrations were normal. Urine total protein distribution by SDS-PAGE and the B/sub 2/M excretion rate were also normal. These data imply that the nephrotoxicity of Cd and Hg are different than that of Pb. The authors speculate on what might account for this difference. This study suggests that when examining a population exposed to Pb, the finding of tubular proteinuria should alert investigators to search for the presence of other toxic agents.

  3. Enhanced Leads and Appointment System

    Data.gov (United States)

    Social Security Administration — The data asset contains information on current or upcoming appointments, individuals who will be attending the appointment, potential intent to file a claim (lead),...

  4. Knockout of Tmem70 alters biogenesis of ATP synthase and leads to embryonal lethality in mice

    Czech Academy of Sciences Publication Activity Database

    Vrbacký, Marek; Kovalčíková, Jana; Chawengsaksophak, Kallayanee; Beck, Inken; Mráček, Tomáš; Nůsková, Hana; Sedmera, David; Papoušek, František; Kolář, František; Sobol, Margaryta; Hozák, Pavel; Sedláček, Radislav; Houštěk, Josef

    2016-01-01

    Roč. 25, č. 21 (2016), s. 4674-4685 ISSN 0964-6906 R&D Projects: GA ČR(CZ) GB14-36804G; GA MŠk(CZ) LL1204; GA MŠk(CZ) ED1.1.00/02.0109; GA TA ČR(CZ) TE01020118; GA MŠk(CZ) LM2015062; GA MZd(CZ) NV16-33018A; GA MŠk(CZ) LM2015040 Institutional support: RVO:67985823 ; RVO:68378050 Keywords : mouse knockout * mitochondria * ATP synthase * TMEM70 * biogenesis * mitochondrial disease s Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.340, year: 2016

  5. BRCA1 haploinsufficiency leads to altered expression of genes involved in cellular proliferation and development.

    Directory of Open Access Journals (Sweden)

    Harriet E Feilotter

    Full Text Available The assessment of BRCA1 and BRCA2 coding sequences to identify pathogenic mutations associated with inherited breast/ovarian cancer syndrome has provided a method to identify high-risk individuals, allowing them to seek preventative treatments and strategies. However, the current test is expensive, and cannot differentiate between pathogenic variants and those that may be benign. Focusing only on one of the two BRCA partners, we have developed a biological assay for haploinsufficiency of BRCA1. Using a series of EBV-transformed cell lines, we explored gene expression patterns in cells that were BRCA1 wildtype compared to those that carried (heterozygous BRCA1 pathogenic mutations. We identified a subset of 43 genes whose combined expression pattern is a sensitive predictor of BRCA1 status. The gene set was disproportionately made up of genes involved in cellular differentiation, lending credence to the hypothesis that single copy loss of BRCA1 function may impact differentiation, rendering cells more susceptible to undergoing malignant processes.

  6. Regulation of ex vivo tyrosine hydroxylase (TH) activity is not altered by chronic lead (Pb) exposure

    International Nuclear Information System (INIS)

    Lasley, S.M.; Green, M.C.

    1991-01-01

    Previous studies have suggested that chronic Pb exposure results in impaired regulation of CNS dopamine (DA) synthesis in rats. The present study was designed to directly assess TH activity in exposed animals compared to controls, employing a pharmacological model that assesses the functional status of dopaminergic synthesis-modulating autoreceptors. At birth dams received 0.2% Pb acetate in drinking water. Offspring were weaned to and maintained on the same solution until termination at 60 or 120 days. Rats were given saline or a DA agonist (EMD 23448 or CGS 15855A) 45 min before sacrifice followed 15 min later by gamma-butyrolactone (GBL). Regional TH activity was measured by a modification of the tritium release method. DA content was determined by liquid chromatography. The ability of EMD 23448 to prevent the GBL-induced increase in DA content was significantly diminished in caudate-putamen (C-P) of exposed rats compared to controls, similar to previous observations. However, an analogous effect of Pb on TH activity in this drug model was not observed using CGS 15855A in rats either 60 or 120 days of age. These findings suggest that chronic Pb exposure has no effect on autoreceptor-mediated regulation of TH in DA neurons when TH activity is measured ex vivo

  7. Gene deletion of cytosolic ATP: citrate lyase leads to altered organic acid production in Aspergillus niger

    DEFF Research Database (Denmark)

    Meijer, Susan Lisette; Nielsen, Michael Lynge; Olsson, Lisbeth

    2009-01-01

    With the availability of the genome sequence of the filamentous fungus Aspergillus niger, the use of targeted genetic modifications has become feasible. This, together with the fact that A. niger is well established industrially, makes this fungus an attractive micro-organism for creating a cell...... factory platform for production of chemicals. Using molecular biology techniques, this study focused on metabolic engineering of A. niger to manipulate its organic acid production in the direction of succinic acid. The gene target for complete gene deletion was cytosolic ATP: citrate lyase (acl), which...... the acl gene. Additionally, the total amount of organic acids produced in the deletion strain was significantly increased. Genome-scale stoichiometric metabolic model predictions can be used for identifying gene targets. Deletion of the acl led to increased succinic acid production by A. niger....

  8. Peripheral blood signatures of lead exposure.

    Directory of Open Access Journals (Sweden)

    Heather G LaBreche

    Full Text Available BACKGROUND: Current evidence indicates that even low-level lead (Pb exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. METHODOLOGY/PRINCIPAL FINDING: Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. CONCLUSIONS/SIGNIFICANCE: The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway.

  9. On the pathologically altered pulmonary pattern

    International Nuclear Information System (INIS)

    Ginzburg, M.A.; Kinoshenko, Yu.T.

    1982-01-01

    The notions ''normal'' and ''pathologically altered pulmonary pattern'' are specified. A grouping of lung pattern alterations based on morphopathogenetic features is provided: blood and lymphatic vascular alterations, changes in the bronchi, lung stroma, and combined alterations. Radiologic appearance of the altered pulmonary pattern is classified in keeping with the basic principles of an X-ray shade examination. The terms, such as ''enriching'', ''strengthening'', ''deformation'', etc., used for describing the pathologically altered pulmonary pattern are defined

  10. Surgical removal of infected transvenous pacemaker leads.

    Science.gov (United States)

    Frame, R; Brodman, R F; Furman, S; Andrews, C A; Gross, J N

    1993-12-01

    Infection, though uncommon, can be the most lethal of all potential complications following transvenous pacemaker implantation. Eradication of infection associated with pacemakers requires complete removal of all hardware, including inactive leads. Since 1972, 5,089 patients have had 8,508 pacemaker generators implanted at Montefiore Medical Center. There were 91 infections (1.06%); four of our patients required surgical removal. Nine additional patients were referred for surgical removal of infected transvenous pacemaker leads from other institutions. Surgical methods for removal included use of cardiopulmonary bypass or inflow occlusion. Surgery may be safely used in unstable or elderly patients and should not be reserved as a last resort. This article reviews our surgical experience removing infected pacemaker leads at Montefiore Medical Center.

  11. Radiation Exposure Alters Expression of Metabolic Enzyme Genes In Mice

    Science.gov (United States)

    Wotring, Virginia E.; Mangala, L. S.; Zhang, Y.; Wu, H.

    2010-01-01

    Most pharmaceuticals are metabolized by the liver. The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Because of the importance of the liver in drug metabolism it is important to understand the effects of spaceflight on the enzymes of the liver. Exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments. This study is an effort to examine the effects of adaptive mechanisms that may be triggered by early exposure to low radiation doses. Using procedures approved by the JSC Animal Care & Use Committee, C57 male mice were exposed to Cs-137 in groups: controls, low dose (50 mGy), high dose (6Gy) and a fourth group that received both radiation doses separated by 24 hours. Animals were anesthetized and sacrificed 4 hours after their last radiation exposure. Livers were removed immediately and flash-frozen in liquid nitrogen. Tissue was homogenized, RNA extracted and purified (Absolutely RNA, Agilent). Quality of RNA samples was evaluated (Agilent Bioanalyzer 2100). Complementary DNA was prepared from high-quality RNA samples, and used to run RT-qPCR screening arrays for DNA Repair and Drug Metabolism (SuperArray, SABiosciences/Qiagen; BioRad Cfx96 qPCR System). Of 91 drug metabolism genes examined, expression of 7 was altered by at least one treatment condition. Genes that had elevated expression include those that metabolize promethazine and steroids (4-8-fold), many that reduce oxidation products, and one that reduces heavy metal exposure (greater than 200-fold). Of the 91 DNA repair and general metabolism genes examined, expression of 14 was altered by at least one treatment condition. These gene expression changes are likely homeostatic and could lead to development of new radioprotective countermeasures.

  12. Anthropogenic Water Uses and River Flow Regime Alterations by Dams

    Science.gov (United States)

    Ferrazzi, M.; Botter, G.

    2017-12-01

    Dams and impoundments have been designed to reconcile the systematic conflict between patterns of anthropogenic water uses and the temporal variability of river flows. Over the past seven decades, population growth and economic development led to a marked increase in the number of these water infrastructures, so that unregulated free-flowing rivers are now rare in developed countries and alterations of the hydrologic cycle at global scale have to be properly considered and characterized. Therefore, improving our understanding of the influence of dams and reservoirs on hydrologic regimes is going to play a key role in water planning and management. In this study, a physically based analytic approach is combined to extensive hydrologic data to investigate natural flow regime alterations downstream of dams in the Central-Eastern United States. These representative case studies span a wide range of different uses, including flood control, water supply and hydropower production. Our analysis reveals that the most evident effects of flood control through dams is a decrease in the intra-seasonal variability of flows, whose extent is controlled by the ratio between the storage capacity for flood control and the average incoming streamflow. Conversely, reservoirs used for water supply lead to an increase of daily streamflow variability and an enhanced inter-catchment heterogeneity. Over the last decades, the supply of fresh water required to sustain human populations has become a major concern at global scale. Accordingly, the number of reservoirs devoted to water supply increased by 50% in the US. This pattern foreshadows a possible shift in the cumulative effect of dams on river flow regimes in terms of inter-catchment homogenization and intra-annual flow variability.

  13. Altered choroid plexus gene expression in major depressive disorder

    Directory of Open Access Journals (Sweden)

    Cortney Ann Turner

    2014-04-01

    Full Text Available Given the emergent interest in biomarkers for mood disorders, we assessed gene expression in the choroid plexus, the region that produces cerebrospinal fluid (CSF, in individuals with major depressive disorder (MDD. Genes that are expressed in the choroid plexus (CP can be secreted into the CSF and may be potential biomarker candidates. Given that we have previously shown that fibroblast growth factor family members are differentially expressed in post-mortem brain of subjects with MDD and the CP is a known source of growth factors in the brain, we posed the question whether growth factor dysregulation would be found in the CP of subjects with MDD. We performed laser capture microscopy of the choroid plexus at the level of the hippocampus in subjects with MDD and psychiatrically normal controls. We then extracted, amplified, labeled and hybridized the cRNA to Illumina BeadChips to assess gene expression. In controls, the most highly abundant known transcript was transthyretin. Moreover, half of the 14 most highly expressed transcripts in controls encode ribosomal proteins. Using BeadStudio software, we identified 169 transcripts differentially expressed (p< 0.05 between control and MDD samples. Using pathway analysis we noted that the top network altered in subjects with MDD included multiple members of the transforming growth factor-beta (TGFβ pathway. Quantitative real-time PCR (qRT-PCR confirmed downregulation of several transcripts that interact with the extracellular matrix in subjects with MDD. These results suggest that there may be an altered cytoskeleton in the choroid plexus in MDD subjects that may lead to a disrupted blood-CSF-brain barrier.

  14. Toxicokinetics of lead in lactating and nonlactating mice.

    Science.gov (United States)

    Hallén, I P; Jönsson, S; Karlsson, M O; Oskarsson, A

    1996-02-01

    Toxicokinetics of lead in lactating and nonlactating mice were studied after a single intravenous injection of 0.05 mg of lead (2.5 mCi 203Pb)/kg. Lead concentrations in blood, plasma, and milk were measured for 10 days following dosing. The volume of distribution based on plasma lead was more than two times larger in lactating than in nonlactating mice, 133 and 58 liter/kg, respectively. Plasma lead clearance in lactating mice was 4.25 liter/hr/kg compared with 1.07 liter/hr/kg in nonlactating mice. However, no such pronounced difference in blood lead clearance was found between the two groups, indicating that this parameter does not reveal the kinetic characteristics during lactation. Milk was found to be an additional route of excretion for lead. About 1/3 of the administered dose of lead was excreted in milk. Accordingly, milk clearance contributed to 1/3 of the total plasma clearance in the mice. The relationships of lead in plasma to lead in whole blood as well as lead in milk to lead in whole blood were nonlinear, with a relatively higher increase in plasma and in milk lead levels at higher blood lead levels. This nonlinearity may be explained by a reduced uptake of lead in erythrocytes as the lead binding sites of these cells become saturated. In lactating mice, the maximum binding capacity of lead in red blood cells was even lower than in nonlactating mice. Similar nonlinear relationship have have also been found in human studies although at much higher levels of lead in blood. The milk:plasma concentration ratio for lead was found to be between 50 and 100 after 24 hr, demonstrating a much more efficient excretion of lead into milk than what is known from human studies. Differences in the milk composition may be one explanation for the species differences in milk excretion of lead. The present study shows that physiological changes during lactation alter the pharmacokinetics of lead in mice.

  15. Structural Optimization Including Centrifugal and Coriolis Effects

    Science.gov (United States)

    1988-01-01

    the desired frequency changes with excellent accuracy. MSC/ NASTRAN finite element solution sequences were modified to incorporate rotary effects. DMAP ...properties can be altered by a nonlinear change factor. These manipulations may be done by selective use of the MATMOD DMAP module. In the MSC/ NASTRAN ...Examples were carried out using the general purpose software package MSC/ NASTRAN and ADS (Automated Design Synthesis). "I OTIC copy INSpE TE 6

  16. β-adrenergic receptor-dependent alterations in murine cardiac transcript expression are differentially regulated by gefitinib in vivo.

    Directory of Open Access Journals (Sweden)

    Jennifer A Talarico

    Full Text Available β-adrenergic receptor (βAR-mediated transactivation of epidermal growth factor receptor (EGFR has been shown to promote cardioprotection in a mouse model of heart failure and we recently showed that this mechanism leads to enhanced cell survival in part via regulation of apoptotic transcript expression in isolated primary rat neonatal cardiomyocytes. Thus, we hypothesized that this process could regulate cardiac transcript expression in vivo. To comprehensively assess cardiac transcript alterations in response to acute βAR-dependent EGFR transactivation, we performed whole transcriptome analysis of hearts from C57BL/6 mice given i.p. injections of the βAR agonist isoproterenol in the presence or absence of the EGFR antagonist gefitinib for 1 hour. Total cardiac RNA from each treatment group underwent transcriptome analysis, revealing a substantial number of transcripts regulated by each treatment. Gefitinib alone significantly altered the expression of 405 transcripts, while isoproterenol either alone or in conjunction with gefitinib significantly altered 493 and 698 distinct transcripts, respectively. Further statistical analysis was performed, confirming 473 transcripts whose regulation by isoproterenol were significantly altered by gefitinib (isoproterenol-induced up/downregulation antagonized/promoted by gefinitib, including several known to be involved in the regulation of numerous processes including cell death and survival. Thus, βAR-dependent regulation of cardiac transcript expression in vivo can be modulated by the EGFR antagonist gefitinib.

  17. Effects of lead shot ingestion on delta-aminolevulinic acid dehydratase activity, hemoglobin concentration, and serum chemistry in bald eagles

    Science.gov (United States)

    Hoffman, D.J.; Pattee, O.H.; Wiemeyer, Stanley N.; Mulhern, B.

    1981-01-01

    Lead shot ingestion by bald eagles (Haliaeetus leucocephalus) is considered to be widespread and has been implicated in the death of eagles in nature. It was recently demonstrated under experimental conditions that ingestion of as few as 10 lead shot resulted in death within 12 to 20 days. In the present study hematological responses to lead toxicity including red blood cell ALAD activity, hemoglobin concentration and 23 different blood serum chemistries were examined in five captive bald eagles that were unsuitable for rehabilitation and release. Eagles were dosed by force-feeding with 10 lead shot; they were redosed if regurgitation occurred. Red blood cell ALAD activity was inhibited by nearly 80% within 24 hours when mean blood lead concentration had increased to 0.8 parts per million (ppm). By the end of 1 week there was a significant decrease (20-25%) in hematocrit and hemoglobin, and the mean blood lead concentration was over 3 ppm. Within as little as 1-2 weeks after dosing, significant elevations in serum creatinine and serum alanine aminotransferase occurred, as well as a significant decrease in the ratio of serum aspartic aminotransferase to serum alanine aminotransferase. The mean blood lead concentration was over 5 ppm by the end of 2 weeks. These changes in serum chemistry may be indicative of kidney and liver alterations.

  18. Lead behavior in abalone shell

    Science.gov (United States)

    Hirao, Yoshimitsu; Matsumoto, Akikazu; Yamakawa, Hiroshi; Maeda, Masaru; Kimura, Kan

    1994-08-01

    In order to gain information about the behavior of heavy metals in biological assimilation processes in a marine food chain and to investigate the possibility that lead pollution in a marine environment can be estimated by measurement of a small number of key materials from such a food chain, muscle and shell were analyzed from abalone ( Haliotis) from a shallow water locality in a Japanese coastal region. Lead concentrations in muscle were about 26 ppb for abalone of approximately 3 years old and decreased systematically with increasing age of animals sampled, to about 3.3 ppb for a specimen approximately 8 years old. Lead concentrations in shell material gradually decreased also, from 150 ppb to 82 ppb in the oldest specimen. The decrease of concentration in tissues with increasing age indicates that a mechanism for exclusion of lead during tissue growth becomes more efficient with age. Along the food chain in which abalone is the final stage, lead was enriched at the first stage, from seawater to algae, by a factor of 100. Lead was diminished at all subsequent stages of the chain. Tissue of artificially cultured abalone had four times higher lead values compared to abalone grown in natural conditions, and this appears to reflect the fact that lead concentration was three times higher in seawater in the cultured environment.

  19. Lead-free primary explosives

    Science.gov (United States)

    Huynh, My Hang V.

    2010-06-22

    Lead-free primary explosives of the formula (cat).sub.Y[M.sup.II(T).sub.X(H.sub.2O).sub.6-X].sub.Z, where T is 5-nitrotetrazolate, and syntheses thereof are described. Substantially stoichiometric equivalents of the reactants lead to high yields of pure compositions thereby avoiding dangerous purification steps.

  20. Blood Test: Lead (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Blood Test: Lead KidsHealth / For Parents / Blood Test: Lead What's ... español Análisis de sangre: plomo What Is a Blood Test? A blood test is when a sample of ...

  1. Environmental lead exposure among preschool children in Shanghai, China: blood lead levels and risk factors.

    Directory of Open Access Journals (Sweden)

    Jia Cao

    Full Text Available OBJECTIVE: To determine blood lead levels and to identify related risk factors among children in Shanghai; to explore the lead change trend of children after industrial transformation and to provide data for policy development to control environmental lead pollution in Shanghai. METHODS: A stratified-clustered-random sampling method was used. A tungsten atomizer absorption spectrophotometer was employed to determine blood lead levels. RESULTS: The arithmetic mean, geometric mean and median of blood lead levels of 0- to 6-year-old children from Shanghai were 22.49 µg/L, 19.65 µg/L and 19.5 µg/L, including 0.26% (6/2291 with concentrations ≥100 µg/L and 2.7% (61/2291 with concentrations ≥50 µg/L. Boys' levels (23.57 µg/L were greater than those of girls (21.2 µg/L. The blood lead levels increased with age. This survey showed that the Chongming district was the highest and Yangpu district was the lowest, this result is completely opposite with the earlier survey in Shanghai. Risk factors for lead contamination included housing environment, parents' education levels, social status, hobbies, and children's nutritional status. CONCLUSIONS: The blood lead levels of children in Shanghai were lower than the earlier data of Shanghai and those of published studies in China, but higher than the blood lead levels of developed countries. The blood lead levels of urban districts are higher than the central districts with the industrial transformation. Society and the government should take an active interest in childhood lead poisoning of urban areas.

  2. Loss of p120 catenin and links to mitotic alterations, inflammation, and skin cancer

    DEFF Research Database (Denmark)

    Perez-Moreno, Mirna; Song, Weimin; Pasolli, H Amalia

    2008-01-01

    Tumor formation involves epigenetic modifications and microenvironmental changes as well as cumulative genetic alterations encompassing somatic mutations, loss of heterozygosity, and aneuploidy. Here, we show that conditional targeting of p120 catenin in mice leads to progressive development of s...

  3. DEVELOPMENTAL HYPOTHYROIDISM ALTERS SYNAPTIC TRANSMISSION IN DENTATE GYRUS AND AREA CA1 OF HIPPOCAMPUS.

    Science.gov (United States)

    Hypothyroidism during critical periods of brain developmental leads to learning deficits and alterations in hippocampal structure. Neurophysiological properties of the hippocampus, however, have not been well characterized. The present study examined field potentials evoked in...

  4. Brain Rhythms Connect Impaired Inhibition to Altered Cognition in Schizophrenia

    Science.gov (United States)

    Pittman-Polletta, Benjamin R.; Kocsis, Bernat; Vijayan, Sujith; Whittington, Miles A.; Kopell, Nancy J.

    2015-01-01

    In recent years, schizophrenia research has focused on inhibitory interneuron dysfunction at the level of neurobiology, and on cognitive impairments at the psychological level. Reviewing both experimental and computational findings, we show how the temporal structure of the activity of neuronal populations, exemplified by brain rhythms, can begin to bridge these levels of complexity. Oscillations in neuronal activity tie the pathophysiology of schizophrenia to alterations in local processing and large-scale coordination, and these alterations in turn can lead to the cognitive and perceptual disturbances observed in schizophrenia. PMID:25850619

  5. Interaction of lead acetate with atrial natriuretic factor in rats

    International Nuclear Information System (INIS)

    Giridhar, J.; Isom, G.E.

    1990-01-01

    Lead exposure alters cardiovascular function and has been implicated in the etiology of hypertension. Therefore it was of interest to study the short term effect of lead treatment on atrial natriuretic factor (ANF). Male Sprague Dawley rats were randomly divided into 5 groups containing 4 animals each and injected intraperitoneally with normal saline (control), 0.01, 0.1, 0.5 or 1.0 mg/kg of body weight with lead acetate solution twice a day for 7 days, and then maintained for a period of 30 days. During this period water consumption and urine volume were measured daily. At the end of the 30 day period, immunoreactive levels of ANF in hypothalamus, atria and plasma were measured by radioimmunoassay. Lead treatment did not alter water consumption, but significantly decreased urine output. At all doses, lead produced a decrease in hypothalamic content of ANF and slightly increased atrial levels. The content of ANF in plasma was decreased. The changes in ANF content indicate that lead interacts with the hormonal regulation of the cardiovascular system and these observations may relate to the cardiovascular toxicity of this heavy metal

  6. Biosorption of lead phosphates by lead-tolerant bacteria as a mechanism for lead immobilization.

    Science.gov (United States)

    Rodríguez-Sánchez, Viridiana; Guzmán-Moreno, Jesús; Rodríguez-González, Vicente; Flores-de la Torre, Juan Armando; Ramírez-Santoyo, Rosa María; Vidales-Rodríguez, Luz Elena

    2017-08-01

    The study of metal-tolerant bacteria is important for bioremediation of contaminated environments and development of green technologies for material synthesis due to their potential to transform toxic metal ions into less toxic compounds by mechanisms such as reduction, oxidation and/or sequestration. In this study, we report the isolation of seven lead-tolerant bacteria from a metal-contaminated site at Zacatecas, México. The bacteria were identified as members of the Staphylococcus and Bacillus genera by microscopic, biochemical and 16S rDNA analyses. Minimal inhibitory concentration of these isolates was established between 4.5 and 7.0 mM of Pb(NO 3 ) 2 in solid and 1.0-4.0 mM of Pb(NO 3 ) 2 in liquid media. A quantitative analysis of the lead associated to bacterial biomass in growing cultures, revealed that the percentage of lead associated to biomass was between 1 and 37% in the PbT isolates. A mechanism of complexation/biosorption of lead ions as inorganic phosphates (lead hydroxyapatite and pyromorphite) in bacterial biomass, was determined by Fourier transform infrared spectroscopy and X-ray diffraction analyses. Thus, the ability of the lead-tolerant isolates to transform lead ions into stable and highly insoluble lead minerals make them potentially useful for immobilization of lead in mining waste.

  7. Obesogenic diets alter metabolism in mice.

    Science.gov (United States)

    Showalter, Megan R; Nonnecke, Eric B; Linderholm, A L; Cajka, Tomas; Sa, Michael R; Lönnerdal, Bo; Kenyon, Nicholas J; Fiehn, Oliver

    2018-01-01

    Obesity and accompanying metabolic disease is negatively correlated with lung health yet the exact mechanisms by which obesity affects the lung are not well characterized. Since obesity is associated with lung diseases as chronic bronchitis and asthma, we designed a series of experiments to measure changes in lung metabolism in mice fed obesogenic diets. Mice were fed either control or high fat/sugar diet (45%kcal fat/17%kcal sucrose), or very high fat diet (60%kcal fat/7% sucrose) for 150 days. We performed untargeted metabolomics by GC-TOFMS and HILIC-QTOFMS and lipidomics by RPLC-QTOFMS to reveal global changes in lung metabolism resulting from obesity and diet composition. From a total of 447 detected metabolites, we found 91 metabolite and lipid species significantly altered in mouse lung tissues upon dietary treatments. Significantly altered metabolites included complex lipids, free fatty acids, energy metabolites, amino acids and adenosine and NAD pathway members. While some metabolites were altered in both obese groups compared to control, others were different between obesogenic diet groups. Furthermore, a comparison of changes between lung, kidney and liver tissues indicated few metabolic changes were shared across organs, suggesting the lung is an independent metabolic organ. These results indicate obesity and diet composition have direct mechanistic effects on composition of the lung metabolome, which may contribute to disease progression by lung-specific pathways.

  8. Umbilical cord blood lead levels in California

    Energy Technology Data Exchange (ETDEWEB)

    Satin, K.P.; Neutra, R.R.; Guirguis, G.; Flessel, P. (California Department of Health Services, Berkeley (USA))

    1991-05-01

    During the fall of 1984, we conducted a survey of umbilical cord blood lead levels of 723 live births that occurred at 5 hospitals located in 5 cities in California. Historical ambient air lead levels were used as a qualitative surrogate of air and dust exposure. The area-specific cord blood means (all means {approximately} 5 micrograms/dl), medians, deciles, and distributions did not vary among locations. The California distributions included means that were lower than the 6.6 micrograms/dl reported in Needleman et al.'s Boston study in 1979. Indeed, the entire California distribution was shifted to the left of the Boston study distribution, even though 3% of the California cord lead levels exceeded 10 micrograms/dl--the level above which Needleman et al. have documented psychoneurological effects in children during the first few years of life. Fourteen percent of premature babies had cord blood lead levels above 10 micrograms/dl. The association between prematurity (i.e., less than 260 d gestation) and elevated (greater than 5 micrograms/dl) cord blood lead was observed in all hospitals and yielded a relative risk of 2.9 (95% CI: .9, 9.2) and a population attributable risk of 47%. Further research is needed to confirm this association and to explore the roles of endogenous and exogenous sources of lead exposure to the mothers who give birth to premature infants.

  9. Remediation of lead-contaminated soils

    International Nuclear Information System (INIS)

    Peters, R.W.; Shem, L.

    1992-01-01

    Excavation and transport of soil contaminated with heavy metals has generally been the standard remediation technique for treatment of heavy-metal-contaminated soils. This approach is not a permanent solution; moreover, off-site shipment and disposal of contaminated soil involves high expense, liability, and appropriate regulatory approval. Recently, a number of other techniques have been investigated for treating such contaminated sites, including flotation, solidification/stabilization, vitrification, and chemical extraction. This paper reports the results of a laboratory investigation determining the efficiency of using chelating agents to extract lead from contaminated soils. Lead concentrations in the soils ranged from 500 to 10,000 mg/kg. Ethylenediaminetetraacetic acid (EDTA) and nitrilotriacetic acid (NTA) were examined for their potential extractive capabilities. Concentrations of the chelating agents ranged from 0.01 to 0.10 M. The pH of the suspensions in which the extractions were performed ranged from 4 to 12. Results showed that the removal of lead using NTA and water was ph-dependent, whereas the removal of lead using EDTA was ph-insensitive. Maximum removals of lead were 68.7%,19.1%, and 7.3% using EDTA, NTA, and water, respectively (as compared with initial lead concentrations)

  10. Leading Millennials Motivating And Leading Millennial Service Members

    Science.gov (United States)

    2016-02-20

    mentioned, compared to Baby Boomers and many in Generation X, Millennials have grown up with instantaneous access to limitless information from...www.eremedia.com/ere/helicopter-parents/ Internet ; accessed 12December 2015. 14 Cheryl R. Sturko Grossman, “Gen Y,” Youthwork Information Brief, No...AIR WAR COLLEGE AIR UNIVERSITY LEADING MILLENNIALS MOTIVATING AND LEADING MILLENNIAL SERVICE MEMBERS by Joanne MacGregor, LTC

  11. Art as Alterity in Education

    Science.gov (United States)

    Zhao, Guoping

    2014-01-01

    In education, art has often been perceived as entertainment and decoration and is the first subject to go when there are budget cuts or test-score pressures. Drawing on Emmanuel Lévinas's idea of the primacy of radical alterity that breaks the totality of our being, enables self-transformation and ethics, and ensures community as a totality…

  12. Peary, Verifiability, and Altered Data

    Science.gov (United States)

    Rawlins, Dennis

    1991-01-01

    Robert Peary's alleged 1909 sledge-achievement of the North Pole is critically examined for credibility and consistency, with respect to terrestrial magnetism, solar-altitude, drift, and written & eyewitness testimony. Several alterations of the record are detected, and the dubiousness of navigation without determining longitude is emphasized.

  13. integIRTy: a method to identify genes altered in cancer by accounting for multiple mechanisms of regulation using item response theory.

    Science.gov (United States)

    Tong, Pan; Coombes, Kevin R

    2012-11-15

    Identifying genes altered in cancer plays a crucial role in both understanding the mechanism of carcinogenesis and developing novel therapeutics. It is known that there are various mechanisms of regulation that can lead to gene dysfunction, including copy number change, methylation, abnormal expression, mutation and so on. Nowadays, all these types of alterations can be simultaneously interrogated by different types of assays. Although many methods have been proposed to identify altered genes from a single assay, there is no method that can deal with multiple assays accounting for different alteration types systematically. In this article, we propose a novel method, integration using item response theory (integIRTy), to identify altered genes by using item response theory that allows integrated analysis of multiple high-throughput assays. When applied to a single assay, the proposed method is more robust and reliable than conventional methods such as Student's t-test or the Wilcoxon rank-sum test. When used to integrate multiple assays, integIRTy can identify novel-altered genes that cannot be found by looking at individual assay separately. We applied integIRTy to three public cancer datasets (ovarian carcinoma, breast cancer, glioblastoma) for cross-assay type integration which all show encouraging results. The R package integIRTy is available at the web site http://bioinformatics.mdanderson.org/main/OOMPA:Overview. kcoombes@mdanderson.org. Supplementary data are available at Bioinformatics online.

  14. Lead Toxicity Risks in Gunshot Victims.

    Directory of Open Access Journals (Sweden)

    Gabriel Costa Serrão de Araújo

    Full Text Available Gunshot wounds require surgeons to decide whether to remove or leave bullet fragments in the body. Surgeons also decide how to follow up with patients who have lead fragments retained in their body. Current literature recommends to remove only intra-articular fragments without the need for a follow-up for patients with the metal retained. Therefore, this study investigates chronic lead toxicity for gunshot wounds.The study was performed in the metropolitan area of Rio de Janeiro/Brazil, between 2013 and 2015. It was a case-control study that included 45 victims of gunshot lesions with metallic fragments retained for more than 6 months. The 45 controls were matched for gender, age, and race. We compared the lead blood levels and frequency of symptoms.The control group had average blood lead levels of 2.17 μg/dL (95% Confidence Interval [CI]; 1.71-2.63 and median 2.1 μg/dL. The case group had average values of 9.01 μg/dL (CI; 6.07-11.96 and median values of 6.5 μg/dL with p-values < = 0.001. The case group reported the following more frequently: irritancy, bad mood, headache, memory losses, daylight drowsiness, myalgia, weakness, abdominal pain, joint pain, trembling, tingling limbs. There was statistical significance for the differences of symptoms frequencies and for odds ratio between groups.Although the mean lead levels found were lower than the current laboratory references, low levels have been associated with both rising morbidity and mortality. The WHO stated: "There is no known level of lead exposure that is considered safe". In conclusion, this work showed that bullets retained in the body are not innocuous. There are impacts in the blood lead levels and symptoms related to it, even with few fragments, extra-articular located or existing with low blood lead levels.

  15. Blood lead levels, ALAD gene polymorphisms, and mortality.

    Science.gov (United States)

    van Bemmel, Dana M; Li, Yan; McLean, Jody; Chang, Man-Huei; Dowling, Nicole F; Graubard, Barry; Rajaraman, Preetha

    2011-03-01

    Previous analyses from the National Health and Nutrition Examination Survey (NHANES III) have found that elevated blood lead levels may be associated with cardiovascular mortality, cancer mortality, and all-cause mortality. The 5-aminolevulinic acid dehydratase (ALAD) G177C genetic polymorphism (rs 1800435) affects lead toxicokinetics and may alter the adverse effects of lead exposure. We examined whether the ALAD G177C single nucleotide polymorphism (SNP) affects the relationship between lead and mortality. We analyzed a subset of 3349 genotyped NHANES III participants at least 40 years of age. Using Cox proportional hazards regression, we estimated the relative risk of all-cause, cardiovascular disease, and cancer mortality by ALAD genotype, and by blood lead levels (lead level and mortality. The adjusted overall relative risk for participants with the variant ALAD genotype was decreased for all-cause mortality (hazards ratio = 0.68; [95% confidence interval = 0.50-0.93]) compared with persons having the common GG genotype. There was some suggestion that higher lead levels were associated with cancer mortality (1.48 [0.92-2.38]). We observed no convincing interaction effect between ALAD genotype and blood lead level on mortality risk. The ALAD genotype may be associated with decreased mortality from all causes and from cancer. This association does not seem to be affected by lead exposure.

  16. Lead (Pb) in Drinking Water

    LENUS (Irish Health Repository)

    2009-01-01

    The application of an acid digestion and subsequent solid-phase extraction (SPE) procedure were implemented as preliminary treatments prior to quantifying the levels of potentially endocrine disrupting metals (EDMs) in a variety of solid and liquid matrices. These included (solid) river sediment, leachate sediment and sewage sludge and also (liquid) river water, landfill leachate, concentrated leachate, sewage influent, and sewage effluent, sampled in the Irish Midlands. The total concentrations of cobalt (Co), cadmium (Cd), copper (Cu), chromium (Cr), nickel (Ni), lead (Pb), zinc (Zn), and manganese (Mn), after extraction and preconcentration, were determined by atomic absorption spectroscopy (AAS). Mercury (Hg) in sediment and sludge was determined using cold-vapour atomic fluorescence spectroscopy (AFS). For sewage sludge maximum values (mg\\/kg(dw)) of 4700 Ni, 1642 Mn, 100.0 Cd, 3400 Zn, 36.70 Co, 750.0 Pb, 485.8 Cr, and 1003 Cu were determined whilst in leachate sediment, maximum values (mg\\/kg(dw)) of 32.10 Ni, 815.0 Mn, 32.78 Cd, 230.3 Zn, 26.73 Co, 3525 Pb, 124.9 Cr, and 50.13 Cu were found. Over several months, the data showed elevated levels in sewage influents, effluents, and sludges compared to a battery of adjacent river water samples and corresponding sediments. There was a definite trend for target values for sediments to be exceeded, while intervention values were only exceeded for cadmium. Overall the pattern in terms of concentration was sewage > leachate > river matrices. A nonparametric assessment of the effect of sewage treatment method on median metal levels in sludge revealed statistically significant differences at the 95% level of confidence for Co, Cr, and Hg and at the 90% level of confidence for Cd.

  17. An alter-centric perspective on employee innovation: The importance of alters' creative self-efficacy and network structure.

    Science.gov (United States)

    Grosser, Travis J; Venkataramani, Vijaya; Labianca, Giuseppe Joe

    2017-09-01

    While most social network studies of employee innovation behavior examine the focal employees' ("egos'") network structure, we employ an alter-centric perspective to study the personal characteristics of employees' network contacts-their "alters"-to better understand employee innovation. Specifically, we examine how the creative self-efficacy (CSE) and innovation behavior of employees' social network contacts affects their ability to generate and implement novel ideas. Hypotheses were tested using a sample of 144 employees in a U.S.-based product development organization. We find that the average CSE of alters in an employee's problem solving network is positively related to that employee's innovation behavior, with this relationship being mediated by these alters' average innovation behavior. The relationship between the alters' average innovation behavior and the employee's own innovation behavior is strengthened when these alters have less dense social networks. Post hoc results suggest that having network contacts with high levels of CSE also leads to an increase in ego's personal CSE 1 year later in cases where the employee's initial level of CSE was relatively low. Implications for theory and practice are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. Altered anterior visual system development following early monocular enucleation

    Directory of Open Access Journals (Sweden)

    Krista R. Kelly

    2014-01-01

    Conclusions: The novel finding of an asymmetry in morphology of the anterior visual system following long-term survival from early monocular enucleation indicates altered postnatal visual development. Possible mechanisms behind this altered development include recruitment of deafferented cells by crossing nasal fibres and/or geniculate cell retention via feedback from primary visual cortex. These data highlight the importance of balanced binocular input during postnatal maturation for typical anterior visual system morphology.

  19. Cholesterol mobilization from hepatic lipid droplets during endotoxemia is altered in obese ob/ob mice.

    Science.gov (United States)

    Arisqueta, Lino; Navarro-Imaz, Hiart; Rueda, Yuri; Fresnedo, Olatz

    2015-10-01

    The innate immune response to pathogens during the acute phase response includes lipid metabolism adaptations. Hepatic triacylglycerol (TG) and cholesteryl ester (CE) storage in and mobilization from lipid droplets (LDs) respond to metabolic changes under the control of liver X receptor (LXR) transactivation and cytokine transduction. To evaluate whether alterations of these mechanisms have an impact in the adaptive response to endotoxemia, we analysed liver metabolism changes in lipopolysaccharide (LPS)-treated ob/ob mice, which show altered metabolic and innate responses and a higher sensitivity to sepsis. Lipid composition of serum lipoproteins and hepatic LDs was determined in wild type and ob/ob mice 24 h after LPS treatment. Liver metabolic profiling was done by measuring enzyme activities and mRNA levels. Increased CE hydrolase activity in LDs from endotoxemic mice was accompanied by a lower content of CE and low or no induction of LXR-mediated expression of genes involved in HDL secretion. The attenuated response in liver lipid mobilization accompanied by the strain-specific cholesterol enrichment of secreted VLDL might lead to accumulation of LDL cholesterol. According to our findings, obese leptin-deficient mice present an altered control of hepatic lipid metabolism responses to LPS, which might be, in part at least, a consequence of impaired LXR. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  20. Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state

    Science.gov (United States)

    Galvan, Adriana; Devergnas, Annaelle; Wichmann, Thomas

    2015-01-01

    In patients with Parkinson’s disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials (LFPs), electroencephalograms (EEGs) or electrocorticograms (ECoGs). Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson’s disease, such as deep brain stimulation (DBS) therapy. PMID:25698937

  1. Altered gene expression profile in a mouse model of SCN8A encephalopathy.

    Science.gov (United States)

    Sprissler, Ryan S; Wagnon, Jacy L; Bunton-Stasyshyn, Rosie K; Meisler, Miriam H; Hammer, Michael F

    2017-02-01

    SCN8A encephalopathy is a severe, early-onset epilepsy disorder resulting from de novo gain-of-function mutations in the voltage-gated sodium channel Na v 1.6. To identify the effects of this disorder on mRNA expression, RNA-seq was performed on brain tissue from a knock-in mouse expressing the patient mutation p.Asn1768Asp (N1768D). RNA was isolated from forebrain, cerebellum, and brainstem both before and after seizure onset, and from age-matched wildtype littermates. Altered transcript profiles were observed only in forebrain and only after seizures. The abundance of 50 transcripts increased more than 3-fold and 15 transcripts decreased more than 3-fold after seizures. The elevated transcripts included two anti-convulsant neuropeptides and more than a dozen genes involved in reactive astrocytosis and response to neuronal damage. There was no change in the level of transcripts encoding other voltage-gated sodium, potassium or calcium channels. Reactive astrocytosis was observed in the hippocampus of mutant mice after seizures. There is considerable overlap between the genes affected in this genetic model of epilepsy and those altered by chemically induced seizures, traumatic brain injury, ischemia, and inflammation. The data support the view that gain-of-function mutations of SCN8A lead to pathogenic alterations in brain function contributing to encephalopathy. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Alterations in Neuronal Activity in Basal Ganglia-Thalamocortical Circuits in the Parkinsonian State

    Directory of Open Access Journals (Sweden)

    Adriana eGalvan

    2015-02-01

    Full Text Available In patients with Parkinson’s disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials, electroencephalograms or electrocorticograms. Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson’s disease, such as deep brain stimulation therapy.

  3. Percutaneous Extraction of Transvenous Permanent Pacemaker/Defibrillator Leads

    Directory of Open Access Journals (Sweden)

    Stylianos Paraskevaidis

    2014-01-01

    Full Text Available Background. Widespread use of cardiovascular implantable electronic devices has inevitably increased the need for lead revision/replacement. We report our experience in percutaneous extraction of transvenous permanent pacemaker/defibrillator leads. Methods. Thirty-six patients admitted to our centre from September 2005 through October 2012 for percutaneous lead extraction were included. Lead removal was attempted using Spectranetics traction-type system (Spectranetics Corp., Colorado, CO, USA and VascoExtor countertraction-type system (Vascomed GmbH, Weil am Rhein, Germany. Results. Lead extraction was attempted in 59 leads from 36 patients (27 men, mean ± SD age 61±5 years, with permanent pacemaker (n=25, defibrillator (n=8, or cardiac resynchronisation therapy (n=3 with a mean ± SD implant duration of 50±23 months. The indications for lead removal included pocket infection (n=23, endocarditis (n=2, and ventricular (n=10 and atrial lead dysfunction (n=1. Traction device was used for 33 leads and countertraction device for 26 leads. Mean ± SD fluoroscopy time was 4±2 minutes/lead for leads implanted 48 months (n=21, P=0.03. Complete procedural success rate was 91.7% and clinical procedural success rate was 100%, while lead procedural success rate was 95%. Conclusions. In conclusion, percutaneous extraction of transvenous permanent pacemaker/defibrillator leads using dedicated removal tools is both feasible and safe.

  4. Exposure to inorganic arsenic can lead to gut microbe perturbations and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Jonathan Choiniere

    2016-09-01

    Full Text Available Arsenic is a carcinogenic environmental factor found in food and drinking water around the world. The mechanisms in which arsenic alters homeostasis are not fully understood. Over the past few decades, light has been shed on varying mechanisms in which arsenic induces cancer. Such mechanisms include gut microbe perturbations, genotoxic effects, and epigenetic modification. Gut microbe perturbations have been shown to increase the level of pathogen-associated molecular patterns such as lipopolysaccharide (LPS leading to uncontained inflammation. Increase in inflammation is the major factor in cirrhosis leading to hepatocellular carcinoma. Alterations in gut permeability and metabolites have also been observed as a fallout of arsenic induced gut microbe modification. The guts proximity and interaction through portal flow make the liver susceptible to gut perturbations and ensuing inflammatory responses. Genotoxic and epigenetic dysregulation induced by arsenic and its toxic metabolites present a more direct mechanism that works synergistically with gut microbe perturbations to induce the incidence of cancers. These pathways combined could be some of the main causes of arsenic-induced carcinogenesis.

  5. The oceanography of winter leads

    Science.gov (United States)

    Morison, J. H.; McPhee, M. G.; Curtin, T. B.; Paulson, C. A.

    1992-07-01

    Leads in pack ice have long been considered important to the thermodynamics of the polar regions. A winter lead affects the ocean around it because it is a density source. As the surface freezes, salt is rejected and forms more dense water which sinks under the lead. This sets up a circulation with freshwater flowing in from the sides near the surface and dense water flowing away from the lead at the base of the mixed layer. If the mixed layer is fully turbulent, this pattern may not occur; rather, the salt rejected at the surface may simply mix into the surface boundary layer. In either event the instability produced at the surface of leads is the primary source of unstable buoyancy flux and, as such, exerts a strong influence on the mixed layer. Here as many as possible of the disparate and almost anecdotal observations of lead oceanography are assembled and combined with theoretical arguments to predict the form and scale of oceanographic disturbances caused by winter leads. The experimental data suggest the velocity disturbances associated with lead convection are about 1-5 cm s-1. These appear as jets near the surface and the base of the mixed layer when ice velocities across the lead are less than about 5 cm s-1. The salinity disturbances are about 0.01 to 0.05 psu. Scaling arguments suggest that the geostrophic currents set up by the lead density disturbances are also of the order of 1-5 cm s-1. The disturbances are most obvious when freezing is rapid and ice velocity is low because the salinity and velocity disturbances in the upper ocean are not smeared out by turbulence. In this vein, lead convection may be characterized at one extreme as free convection in which the density disturbance forces the circulation. At the other extreme, lead convection may be characterized as forced convection in which the density disturbance is mixed rapidly by boundary layer turbulence. The lead number Lo, which is the ratio of the pressure term to the turbulence term in the

  6. Including Students with Severe Disabilities in General Education Settings.

    Science.gov (United States)

    Wisniewski, Lech; Alper, Sandra

    1994-01-01

    This paper presents five systematic phases for bringing about successful regular education inclusion of students with severe disabilities. Phases include develop networks within the community, assess school and community resources, review strategies for integration, install strategies that lead to integration, and develop a system of feedback and…

  7. Restructuring the Public School Curriculum To Include Parenting Education Classes.

    Science.gov (United States)

    Tyree, Carolyn L.; And Others

    Although the current educational climate stresses a back-to-basics approach, there is nonetheless overwhelming evidence of a need for an appropriately structured parenting education program in the public school curriculum. Reasons for this need include the large number of teenage pregnancies and abortions. These lead teens to miss high school…

  8. Histopathology of mallards dosed with lead and selected substitute shot

    Science.gov (United States)

    Locke, L.N.; Irby, H.D.; Bagley, George E.

    1967-01-01

    The histopathological response of male game farm mallards fed lead, three types of plastic-coated lead, two lead-magnesium alloys, iron, copper, zinc-coated iron, and molybdenum-coated iron shot was studied. Mallards fed lead, plastic-coated lead, or lead-magnesium alloy shot developed a similar pathological response, including the formation of acid-fast intranuclear inclusion bodies in the kidneys. Birds fed iron or molybdenum-coated iron shot developed hemosiderosis of the liver. Two of four mallards fed zinc-coated iron shot also developed hemosiderosis of the liver. No lesions were found in mallards fed copper shot.

  9. Portable X-ray Fluorescence and Infrared Fluorescence Imaging Studies of Cadmium Yellow Alteration in Paintings by Edward Munch and Henri matisse in Oslo, Copenhagen, and San Francisco

    DEFF Research Database (Denmark)

    Mass, Jennifer; Uffelman, Erich; Buckley, Barbara

    2016-01-01

    The identification of altered cadmium yellow paints in early modernist works is critical to their stabilization and to the long-term preservation of the paintings in which they occur. The identification of incipient photoalteration of these pigments, before there is visual evidence...... of their chemical degradation, is of particular concern. The alteration of these pigments causes chalking, flaking, fading, and darkening of the yellow paints, leading to irreversible changes in the physical and chemical structure of the paint layer and dramatically altering the appearance of the work. Standoff......-induced visible fluorescence, ultraviolet-induced infrared fluorescence, multispectral imaging, and X-ray fluorescence. Questions addressed included the following: Is the imaging method being tested comprehensive? Is it efficient at surveying an entire painting? Does it reveal the state of preservation...

  10. Alteration and alterability of the anorthosite from Angola

    OpenAIRE

    Simão, J.; Silva, Z. C. G.

    2010-01-01

    Siliceous rocks are widely used as dimension stone but the last decades have registered an increase rate of their alteration when exposed to polluted environments. Anorthosites were treated by acidified solutions of HCl, HN03 and H2S04 simulating acid rain and the response was recorded through different experiments such as on the surface of the polished rock and on the surface of uncovered thin sections. The main components, plagioclase and olivine, both responded in similar ways to each acid...

  11. Ingestion of lead from ammunition and lead concentrations in white-tailed sea eagles (Haliaeetus albicilla) in Sweden.

    Science.gov (United States)

    Helander, B; Axelsson, J; Borg, H; Holm, K; Bignert, A

    2009-10-15

    In this study we show for the first time that lead poisoning from ammunition is a significant mortality factor for white-tailed sea eagle (WSE) (Haliaeetus albicilla) in Sweden. We analyzed 118 WSEs collected between 1981 and 2004 from which both liver and kidney samples could be taken. A total of 22% of all eagles examined had elevated (>6 microg/gd.w.) lead concentrations, indicating exposure to leaded ammunition, and 14% of the individuals had either liver or kidney lead concentrations diagnostic of lethal lead poisoning (>20 microg/gd.w.). Lead concentrations in liver and kidney were significantly correlated. In individuals with lead levels 20 microg/g, concentrations were significantly higher in liver. The lead isotope ratios indicate that the source of lead in individuals with lethal concentrations is different from that of individuals exhibiting background concentrations of lead (10 times higher than concentrations reported for Baltic fish from the same time period. In contrast to other biota there was no decrease in lead concentrations in WSE over the study period. The proportion of lead poisoned WSE remained unchanged over the study period, including two years after a partial ban of lead shot was enforced in 2002 for shallow wetlands. The use of lead in ammunition poses a threat to all raptors potentially feeding on shot game or offal. The removal of offal from shot game and alternatives to leaded ammunition needs to be implemented in order to prevent mortality from lead in raptors and scavengers.

  12. Altered B lymphocyte homeostasis and functions in systemic sclerosis.

    Science.gov (United States)

    Forestier, Alexandra; Guerrier, Thomas; Jouvray, Mathieu; Giovannelli, Jonathan; Lefèvre, Guillaume; Sobanski, Vincent; Hauspie, Carine; Hachulla, Eric; Hatron, Pierre-Yves; Zéphir, Hélène; Vermersch, Patrick; Labalette, Myriam; Launay, David; Dubucquoi, Sylvain

    2018-03-01

    Beyond the production of autoantibodies, B-cells are thought to play a role in systemic sclerosis (SSc) by secreting proinflammatory/profibrotic cytokines. B-cells are a heterogeneous population with different subsets distinguished by their phenotypes and cytokine production. Data about B-cell subsets, cytokine production and intracellular pathways leading to this production are scarce in SSc. The aim of our study was to describe B-cell homeostasis, activation, proliferation, cytokine production in B-cells and serum and B-cell intracellular signaling pathways in SSc. We hypothezided that B-cell homeostasis and cytokine production were altered in SSc and could be explained by serum cytokine as well as by intracellular signaling pathway abnormalities. Forty SSc patients and 20 healthy controls (HC) were prospectively included. B-cell subsets were determined by flow cytometry using CD19, CD21, CD24, CD38, CD27, IgM and IgD. CD25, CD80, CD95, HLA-DR were used to assess B-cell activation. Intracellular production of IL-10 and IL-6 were assessed by flow cytometry after TLR9 and CD40 stimulation. IL-6, IL-10, Ki67, Bcl2 mRNA were quantified in B-cells. Cytokine production was also assessed in sera and supernatants of B-cell culture, using a multiplex approach. Signaling pathways were studied through phosphorylation of mTOR, ERK, STAT3, STAT5 using a flow cytometry approach. We found that SSc patients exhibited an altered peripheral blood B-cell subset distribution, with decreased memory B-cells but increased proportion of naive and CD21 Lo CD38 Lo B-cell subsets. We observed an increased expression of activation markers (CD80, CD95, HLA-DR) on some B-cell subsets, mainly the memory B-cells. Secretion of IL-6, BAFF and CXCL13 were increased in SSc sera. There was no correlation between the peripheral blood B-cell subsets and the serum concentrations of these cytokines. After stimulation, we observed a lower proportion of IL-10 and IL-6 producing B-cells in SSc. Finally, we

  13. Composite material including nanocrystals and methods of making

    Science.gov (United States)

    Bawendi, Moungi G.; Sundar, Vikram C.

    2010-04-06

    Temperature-sensing compositions can include an inorganic material, such as a semiconductor nanocrystal. The nanocrystal can be a dependable and accurate indicator of temperature. The intensity of emission of the nanocrystal varies with temperature and can be highly sensitive to surface temperature. The nanocrystals can be processed with a binder to form a matrix, which can be varied by altering the chemical nature of the surface of the nanocrystal. A nanocrystal with a compatibilizing outer layer can be incorporated into a coating formulation and retain its temperature sensitive emissive properties.

  14. Lead Corrosion in Exhibition Ship Models

    National Research Council Canada - National Science Library

    Wegner, Dana

    1997-01-01

    .... However, lead fittings frequently corrode. Corrosion may be so severe as to completely consume the piece, leaving behind a white or gray residue popularly, and aptly, called "lead disease," "lead rot," "lead cancer," or "lead bloom...

  15. The main factors controlling petrophysical alteration in hydrothermal systems of the Kuril-Kamchatka island arch

    Science.gov (United States)

    Frolova, J.; Ladygin, V.; Rychagov, S.; Shanina, V.; Blyumkina, M.

    2009-04-01

    This report is based on the results of petrophysical studies obtained on a number of hydrothermal systems in the Kuril-Kamchatka island arc (Pauzhetsky, Mutnovsky, Koshelevsky, Essovsky, a volcano of Ebeko, Oceansky). Mineral composition and pore-space structure of primary rocks change intensively during hydrothermal process, results in alteration of petrophysical properties - porosity, density, permeability, hygroscopy, sonic velocity, elastic modulus, mechanical properties, thermal and magnetic characteristics. Petrophysical alterations gradually lead to the change of the structure of hydrothermal system, and its hydrodynamic and temperature regime. The tendency of petrophysical alteration can be different. In some cases rocks "improvement" is observed i.e. consolidation, hardening, decrease of porosity and permeability, removal of hygroscopy. In other cases rocks "deterioration" occurs, i.e. formation of secondary porosity and permeability, a decrease of density, strength, and elastic modulus, and occurrence of hygroscopic moisture. The classical example of cardinal petrophysical alteration is the transformation of hard basalts to plastic clays. The opposite example is the transformation of only slightly consolidates porous tuffs to hard and dense secondary quartzite. The character of petrophysical alteration depends on a number of factors including peculiarities of primary rocks, temperature, pressure and composition of thermal fluids, duration of fluid-rock interaction, and condition of fluid (steam, water, boiling water). The contribution of each factor to change of volcanic rocks properties is considered and analyzed in details. In particular, primary rocks controls speed, intensity and character of petrophysical alterations. Factors favorable for alteration are high porosity and permeability, micro crakes, weak cementation, glassy structure, basaltic composition. Kuril-Kamchatka region represents the volcanic island arch so host rocks in hydrothermal

  16. Effect measure modification of blood lead-air lead slope factors.

    Science.gov (United States)

    Richmond-Bryant, Jennifer; Meng, Qingyu; Cohen, Jonathan; Davis, J Allen; Svendsgaard, David; Brown, James S; Tuttle, Lauren; Hubbard, Heidi; Rice, Joann; Kirrane, Ellen; Vinikoor-Imler, Lisa; Kotchmar, Dennis; Hines, Erin; Ross, Mary

    2015-01-01

    There is abundant literature finding that susceptibility factors, including race and ethnicity, age, and housing, directly influence blood lead levels. No study has explored how susceptibility factors influence the blood lead-air lead relationship nationally. The objective is to evaluate whether susceptibility factors act as effect measure modifiers on the blood lead-air lead relationship. Participant level blood lead data from the 1999 to 2008 National Health and Nutrition Examination Survey were merged with air lead data from the US Environmental Protection Agency. Linear mixed effects models were run with and without an air lead interaction term for age group, sex, housing age, or race/ethnicity to determine whether these factors are effect measure modifiers for all ages combined and for five age brackets. Age group and race/ethnicity were determined to be effect measure modifiers in the all-age model and for some age groups. Being a child (1-5, 6-11, and 12-19 years) or of Mexican-American ethnicity increased the effect estimate. Living in older housing (built before 1950) decreased the effect estimate for all models except for the 1-5-year group, where older housing was an effect measure modifier. These results are consistent with the peer-reviewed literature of time-activity patterns, ventilation, and toxicokinetics.

  17. Climate variation alters the synchrony of host-parasitoid interactions.

    Science.gov (United States)

    Wetherington, Miles T; Jennings, David E; Shrewsbury, Paula M; Duan, Jian J

    2017-10-01

    Observed changes in mean temperature and increased frequency of extreme climate events have already impacted the distributions and phenologies of various organisms, including insects. Although some research has examined how parasitoids will respond to colder temperatures or experimental warming, we know relatively little about how increased variation in temperature and humidity could affect interactions between parasitoids and their hosts. Using a study system consisting of emerald ash borer (EAB), Agrilus planipennis , and its egg parasitoid Oobius agrili , we conducted environmentally controlled laboratory experiments to investigate how increased seasonal climate variation affected the synchrony of host-parasitoid interactions. We hypothesized that increased climate variation would lead to decreases in host and parasitoid survival, host fecundity, and percent parasitism (independent of host density), while also influencing percent diapause in parasitoids. EAB was reared in environmental chambers under four climate variation treatments (standard deviations in temperature of 1.24, 3.00, 3.60, and 4.79°C), while O .  agrili experiments were conducted in the same environmental chambers using a 4 × 3 design (four climate variation treatments × 3 EAB egg densities). We found that EAB fecundity was negatively associated with temperature variation and that temperature variation altered the temporal egg laying distribution of EAB. Additionally, even moderate increases in temperature variation affected parasitoid emergence times, while decreasing percent parasitism and survival. Furthermore, percent diapause in parasitoids was positively associated with humidity variation. Our findings indicate that relatively small changes in the frequency and severity of extreme climate events have the potential to phenologically isolate emerging parasitoids from host eggs, which in the absence of alternative hosts could lead to localized extinctions. More broadly, these results

  18. Lead immobilization in thermally remediated soils and igneous rocks

    International Nuclear Information System (INIS)

    Hickmott, D.D.; Carey, J.W.; Stimac, J.; Larocque, A.; Abell, R.; Gauerke, E.; Eppler, A.

    1997-01-01

    This is the final report for a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The principal goal of this project was to investigate the speciation of lead in the environment at LANL and to determine the feasibility of using thermal remediation methods to immobilize lead in the environment. Lead occurs as pyromorphite [Pb(PO 4 ) 3 (Cl, OH)], cerussite (PbCO 3 ) and galena (PbS) in vapor-phase-altered Bandelier Tuff samples. LANL soils primarily contain cerussite and PbO. Thermal remediation experiments at high temperatures (up to 400 C) suggest that thermal immobilization of highly-reactive Pb compounds in the environment may be feasible, but that this technique is not optimal for more refractory lead phases such as cerussite and PbO

  19. Antiherbivore defenses alter natural selection on plant reproductive traits.

    Science.gov (United States)

    Thompson, Ken A; Johnson, Marc T J

    2016-04-01

    While many studies demonstrate that herbivores alter selection on plant reproductive traits, little is known about whether antiherbivore defenses affect selection on these traits. We hypothesized that antiherbivore defenses could alter selection on reproductive traits by altering trait expression through allocation trade-offs, or by altering interactions with mutualists and/or antagonists. To test our hypothesis, we used white clover, Trifolium repens, which has a Mendelian polymorphism for the production of hydrogen cyanide-a potent antiherbivore defense. We conducted a common garden experiment with 185 clonal families of T. repens that included cyanogenic and acyanogenic genotypes. We quantified resistance to herbivores, and selection on six floral traits and phenology via male and female fitness. Cyanogenesis reduced herbivory but did not alter the expression of reproductive traits through allocation trade-offs. However, the presence of cyanogenic defenses altered natural selection on petal morphology and the number of flowers within inflorescences via female fitness. Herbivory influenced selection on flowers and phenology via female fitness independently of cyanogenesis. Our results demonstrate that both herbivory and antiherbivore defenses alter natural selection on plant reproductive traits. We discuss the significance of these results for understanding how antiherbivore defenses interact with herbivores and pollinators to shape floral evolution. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

  20. Rare earth impact on glass structure and alteration kinetics

    International Nuclear Information System (INIS)

    Molieres, E.

    2012-01-01

    This work is related to the question of the geological deep repository of high-level waste glass. These wastes include fission products and minor actinides, elements which can be simulated by rare earths. As new glass compositions could enable increased rare earth concentrations, it is crucial to know and understand rare earth impact on glass structure on the one hand, and on glass alteration kinetics or their incorporation into an altered layer. This work studied simplified borosilicate glasses in order to limit synergetic effects between rare earths and other elements. Various complementary techniques were used to characterize pristine and altered glasses (solid-high resolution NMR, Raman spectroscopy, fluorescence, SIMS, SAXS). Firstly, the structural role of a rare earth is discussed and is compared to a calcium cation. The local environment of rare earths is also probed. Secondly, rare earth (nature and concentration) impact on several alteration regimes was studied (initial rate, rate drop). Then, after alteration, rare earth elements being retained within the altered layer, the structural impact of rare earth elements (and their local environment) in this alteration layer was also investigated. (author) [fr

  1. Chemosensory alterations and cancer therapies

    International Nuclear Information System (INIS)

    Bartoshuk, L.M.

    1990-01-01

    Taste and olfaction provide sensory information and sensory pleasure. Cancer therapies affect both. Chemotherapy has not been shown to produce dramatic losses of taste or smell, but systematic studies on various chemotherapeutic agents and types of cancer are lacking. Radiation therapy does produce clear losses of both taste and smell. Both chemotherapy and radiation therapy alter the pleasure produced by taste and smell through the formation of conditioned aversions. That is, foods consumed in proximity with the nausea of therapy come to be unpleasant. The impact of conditioned aversions can be diminished by providing a scapegoat food just before therapy. Alterations in foods may be beneficial to the cancer patient. Increasing the concentrations of flavor ingredients can compensate for sensory losses, and providing pureed foods that retain the cognitive integrity of a meal can benefit the patient who has chewing or swallowing problems

  2. Altered Cytoskeleton as a Mitochondrial Decay Signature in the Retinal Pigment Epithelium.

    Science.gov (United States)

    Sripathi, Srinivas R; He, Weilue; Sylvester, O'Donnell; Neksumi, Musa; Um, Ji-Yeon; Dluya, Thagriki; Bernstein, Paul S; Jahng, Wan Jin

    2016-06-01

    Mitochondria mediate energy metabolism, apoptosis, and aging, while mitochondrial disruption leads to age-related diseases that include age-related macular degeneration. Descriptions of mitochondrial morphology have been non-systematic and qualitative, due to lack of knowledge on the molecular mechanism of mitochondrial dynamics. The current study analyzed mitochondrial size, shape, and position quantitatively in retinal pigment epithelial cells (RPE) using a systematic computational model to suggest mitochondrial trafficking under oxidative environment. Our previous proteomic study suggested that prohibitin is a mitochondrial decay biomarker in the RPE. The current study examined the prohibitin interactome map using immunoprecipitation data to determine the indirect signaling on cytoskeletal changes and transcriptional regulation by prohibitin. Immunocytochemistry and immunoprecipitation demonstrated that there is a positive correlation between mitochondrial changes and altered filaments as well as prohibitin interactions with kinesin and unknown proteins in the RPE. Specific cytoskeletal and nuclear protein-binding mechanisms may exist to regulate prohibitin-mediated reactions as key elements, including vimentin and p53, to control apoptosis in mitochondria and the nucleus. Prohibitin may regulate mitochondrial trafficking through unknown proteins that include 110 kDa protein with myosin head domain and 88 kDa protein with cadherin repeat domain. Altered cytoskeleton may represent a mitochondrial decay signature in the RPE. The current study suggests that mitochondrial dynamics and cytoskeletal changes are critical for controlling mitochondrial distribution and function. Further, imbalance of retrograde versus anterograde mitochondrial trafficking may initiate the pathogenic reaction in adult-onset neurodegenerative diseases.

  3. Including risk in the balanced scorecard

    African Journals Online (AJOL)

    kirstam

    then breaking them down into smaller goals that are set in lower hierarchies of the organisation (Cronje & Maritz ... the adoption rates for both frameworks among Johannesburg Stock Exchange (JSE) listed organisations. .... regime. Implementing a successful BSC has been shown to lead to a higher rate of acceptance and ...

  4. Preconception paternal stress in rats alters dendritic morphology and connectivity in the brain of developing male and female offspring.

    Science.gov (United States)

    Harker, A; Raza, S; Williamson, K; Kolb, B; Gibb, R

    2015-09-10

    The goal of this research was to examine the effect of preconception paternal stress (PPS) on the subsequent neurodevelopment and behavior of male and female offspring. Prenatal (gestational) stress has been shown to alter brain morphology in the developing brain, and is presumed to be a factor in the development of some adult psychopathologies. Our hypothesis was that paternal stress in the preconception period could impact brain development in the offspring, leading to behavioral abnormalities later in life. The purpose of this study was to examine the effect of preconception paternal stress on developing male and female offspring brain morphology in five brain areas; medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), parietal cortex (Par1), hippocampus (CA1) and nucleus accumbens (NAc). Alterations in dendritic measures and spine density were observed in each brain area examined in paternal stress offspring. Our two main findings reveal; (1) PPS alters brain morphology and organization and these effects are different than the effects of stress observed at other ages; and, (2) the observed dendritic changes were sexually dimorphic. This study provides direct evidence that PPS modifies brain architecture in developing offspring, including dendritic length, cell complexity, and spine density. Alterations observed may contribute to the later development of psychopathologies and maladaptive behaviors in the offspring. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Alteration of cytokines and chemokines during febrile episodes associated with endothelial cell damage and plasma leakage in dengue hemorrhagic fever.

    Science.gov (United States)

    Butthep, Punnee; Chunhakan, Sirichan; Yoksan, Sutee; Tangnararatchakit, Kanchana; Chuansumrit, Ampaiwan

    2012-12-01

    The leakage of plasma during febrile episodes in dengue-infected patients is a severe condition leading to dengue shock syndrome. Alteration of cytokines/chemokines is suspected to be a major cause of endothelial cell damage in these patients. The study was designed to demonstrate the alteration of cytokines and chemokines in dengue-infected patients during febrile episodes. The blood samples from 164 patients with dengue fever, dengue hemorrhagic fever and other febrile illnesses were collected daily from the day of hospitalization until discharge and also in the convalescent stage. The levels of cytokines/chemokines were determined using a sandwich chemiluminescent immunoassay, and the hematological parameters were examined by the ADVIA hematological analyzer. Two patterns of cytokines/chemokines alteration were detected at different time points during the febrile episode. The increased factors included interleukin (IL)-4, IL-6, IL-8, IL-10, tumor necrosis factor-α, interferon-γ and monocyte chemoattractant protein-1 whereas IL-1β, IL-2, vascular endothelial growth factor and epidermal growth factor were decreased. Several cytokines were correlated with disease severity especially in dengue hemorrhagic fever/dengue shock syndrome patients. The alteration in the cytokine/chemokine kinetics during a febrile episode can be used as a predictor for severe dengue infection. The increased and decreased levels at different time points can indicate the disease progression related to vascular leakage in dengue hemorrhagic fever/dengue shock syndrome patients.

  6. Lead-vacancy-related hole centers in lead tungstate crystals

    Czech Academy of Sciences Publication Activity Database

    Laguta, Valentyn; Nikl, Martin; Zazubovich, S.

    2012-01-01

    Roč. 249, č. 11 (2012), s. 2161-2166 ISSN 0370-1972 R&D Projects: GA AV ČR IAA100100810 Institutional research plan: CEZ:AV0Z10100521 Keywords : hole centers * lead tungstate * thermally stimulated luminescence Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.489, year: 2012

  7. Occupational Health Management in the Lead Industry: The Korean Experience

    Directory of Open Access Journals (Sweden)

    Byung-Kook Lee

    2011-06-01

    Full Text Available In 1967, the problem of occupational lead exposure came to public attention in Korea. Since then, regular progress has been made in lowering workplace lead exposures, instituting new workplace controls, and implementing health examinations of exposed workers. Past serious lead poisoning episodes made it possible to introduce biological monitoring programs on a voluntary basis in high-lead-exposure facilities in Korea. Industry-specific occupational health services for lead workers in Korea during the last 22 years can be categorized into three phases. During the first phase (1988-1993, efforts were directed at increasing awareness among workers about the hazards of lead exposure, biological monitoring of blood zinc protoporphyrin began, and a respiratory protection program was introduced. During the second phase (1994-1997, a computerized health management system for lead workers was developed, blood-lead measurement was added to biologic monitoring, and engineering controls were introduced in the workplace to lower air-lead levels to comply with air-lead regulations. Finally, during the third phase (1998-present, a new biomarker, bone-lead measurement by X-ray fluorescence, was introduced. Bone-lead measurement proved to be useful for assessing body burden and to demonstrate past lead exposure in retired workers. Occupational health service practice for lead workers, including the industry-specific group occupational health system, has brought considerable success in the prevention of lead poisoning and in reducing the lead burden in Korean lead workers during the last several decades. The successful achievement of prevention of lead poisoning in Korea was a result of the combined efforts of lead workers, employers, relevant government agencies, and academic institutes.

  8. Significance of plasma lead levels in normal and lead-intoxicated children.

    Science.gov (United States)

    Rosen, J F; Trinidad, E E

    1974-05-01

    Plasma lead (Pb) levels have been measured in normal and lead-intoxicated children, newborns, and children with sickle cell disease. The results in all groups were contant over a wide range of red cell Pb concentration. These results support the thesis that the red cell represents a large repository for Pb, maintaining plasma Pb concentration within closely defined limits, and that methods other than measurements of plasma Pb will be necessary to uncover a presumably dynamic transport system between red cell and plasma. Indeed, we have demonstrated in vitro that ionized calcium (Ca(2+)) lowers red cell Pb content according to a linear dose-response curve. Ca(2+) may thereby control Pb transport from red cell to plasma, and fluctuations in the concentration of Ca(2+) in serum and extracellular fluid may influence the toxic activities of Pb. In bone organ culture, changes in the concentration of Ca(2+) and phosphate in the medium alter the release of previously incorporated (210)Pb from fetal rat bones in response to parathyroid hormone (PTH). Therefore, both PTH and the ionic milieu of the medium apparently regulate bone Pb metabolism.We would expect that understanding further the dynamics of Pb transport in plasma and bone may lead to a more exact definition of the real hazards of low level Pb toxicity in children.

  9. Significance of Plasma Lead Levels in Normal and Lead-Intoxicated Children*

    Science.gov (United States)

    Rosen, John F.; Trinidad, Emma E.

    1974-01-01

    Plasma lead (Pb) levels have been measured in normal and lead-intoxicated children, newborns, and children with sickle cell disease. The results in all groups were contant over a wide range of red cell Pb concentration. These results support the thesis that the red cell represents a large repository for Pb, maintaining plasma Pb concentration within closely defined limits, and that methods other than measurements of plasma Pb will be necessary to uncover a presumably dynamic transport system between red cell and plasma. Indeed, we have demonstrated in vitro that ionized calcium (Ca2+) lowers red cell Pb content according to a linear dose–response curve. Ca2+ may thereby control Pb transport from red cell to plasma, and fluctuations in the concentration of Ca2+ in serum and extracellular fluid may influence the toxic activities of Pb. In bone organ culture, changes in the concentration of Ca2+ and phosphate in the medium alter the release of previously incorporated 210Pb from fetal rat bones in response to parathyroid hormone (PTH). Therefore, both PTH and the ionic milieu of the medium apparently regulate bone Pb metabolism. We would expect that understanding further the dynamics of Pb transport in plasma and bone may lead to a more exact definition of the real hazards of low level Pb toxicity in children. PMID:4831136

  10. Lead-Related Genetic Loci, Cumulative Lead Exposure and Incident Coronary Heart Disease: The Normative Aging Study.

    Science.gov (United States)

    Ding, Ning; Wang, Xin; Weisskopf, Marc G; Sparrow, David; Schwartz, Joel; Hu, Howard; Park, Sung Kyun

    2016-01-01

    Cumulative exposure to lead is associated with cardiovascular outcomes. Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD), hemochromatosis (HFE), heme oxygenase-1 (HMOX1), vitamin D receptor (VDR), glutathione S-transferase (GST) supergene family (GSTP1, GSTT1, GSTM1), apolipoprotein E (APOE),angiotensin II receptor-1 (AGTR1) and angiotensinogen (AGT) genes, are believed to alter toxicokinetics and/or toxicodynamics of lead. We assessed possible effect modification by genetic polymorphisms in ALAD, HFE, HMOX1, VDR, GSTP1, GSTT1, GSTM1, APOE, AGTR1 and AGT individually and as the genetic risk score (GRS) on the association between cumulative lead exposure and incident coronary heart disease (CHD) events. We used K-shell-X-ray fluorescence to measure bone lead levels. GRS was calculated on the basis of 22 lead-related loci. We constructed Cox proportional hazard models to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CHD. We applied inverse probability weighting to account for potential selection bias due to recruitment into the bone lead sub-study. Significant effect modification was found by VDR, HMOX1, GSTP1, APOE, and AGT genetic polymorphisms when evaluated individually. Further, the bone lead-CHD associations became larger as GRS increases. After adjusting for potential confounders, a HR of CHD was 2.27 (95%CI: 1.50-3.42) with 2-fold increase in patella lead levels, among participants in the top tertile of GRS. We also detected an increasing trend in HRs across tertiles of GRS (p-trend = 0.0063). Our findings suggest that lead-related loci as a whole may play an important role in susceptibility to lead-related CHD risk. These findings need to be validated in a separate cohort containing bone lead, lead-related genetic loci and incident CHD data.

  11. Lead-Related Genetic Loci, Cumulative Lead Exposure and Incident Coronary Heart Disease: The Normative Aging Study.

    Directory of Open Access Journals (Sweden)

    Ning Ding

    Full Text Available Cumulative exposure to lead is associated with cardiovascular outcomes. Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD, hemochromatosis (HFE, heme oxygenase-1 (HMOX1, vitamin D receptor (VDR, glutathione S-transferase (GST supergene family (GSTP1, GSTT1, GSTM1, apolipoprotein E (APOE,angiotensin II receptor-1 (AGTR1 and angiotensinogen (AGT genes, are believed to alter toxicokinetics and/or toxicodynamics of lead.We assessed possible effect modification by genetic polymorphisms in ALAD, HFE, HMOX1, VDR, GSTP1, GSTT1, GSTM1, APOE, AGTR1 and AGT individually and as the genetic risk score (GRS on the association between cumulative lead exposure and incident coronary heart disease (CHD events.We used K-shell-X-ray fluorescence to measure bone lead levels. GRS was calculated on the basis of 22 lead-related loci. We constructed Cox proportional hazard models to compute adjusted hazard ratios (HRs and 95% confidence intervals (CIs for incident CHD. We applied inverse probability weighting to account for potential selection bias due to recruitment into the bone lead sub-study.Significant effect modification was found by VDR, HMOX1, GSTP1, APOE, and AGT genetic polymorphisms when evaluated individually. Further, the bone lead-CHD associations became larger as GRS increases. After adjusting for potential confounders, a HR of CHD was 2.27 (95%CI: 1.50-3.42 with 2-fold increase in patella lead levels, among participants in the top tertile of GRS. We also detected an increasing trend in HRs across tertiles of GRS (p-trend = 0.0063.Our findings suggest that lead-related loci as a whole may play an important role in susceptibility to lead-related CHD risk. These findings need to be validated in a separate cohort containing bone lead, lead-related genetic loci and incident CHD data.

  12. Lead-Related Genetic Loci, Cumulative Lead Exposure and Incident Coronary Heart Disease: The Normative Aging Study

    Science.gov (United States)

    Weisskopf, Marc G.; Sparrow, David; Schwartz, Joel; Hu, Howard; Park, Sung Kyun

    2016-01-01

    Background Cumulative exposure to lead is associated with cardiovascular outcomes. Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD), hemochromatosis (HFE), heme oxygenase-1 (HMOX1), vitamin D receptor (VDR), glutathione S-transferase (GST) supergene family (GSTP1, GSTT1, GSTM1), apolipoprotein E (APOE),angiotensin II receptor-1 (AGTR1) and angiotensinogen (AGT) genes, are believed to alter toxicokinetics and/or toxicodynamics of lead. Objectives We assessed possible effect modification by genetic polymorphisms in ALAD, HFE, HMOX1, VDR, GSTP1, GSTT1, GSTM1, APOE, AGTR1 and AGT individually and as the genetic risk score (GRS) on the association between cumulative lead exposure and incident coronary heart disease (CHD) events. Methods We used K-shell-X-ray fluorescence to measure bone lead levels. GRS was calculated on the basis of 22 lead-related loci. We constructed Cox proportional hazard models to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CHD. We applied inverse probability weighting to account for potential selection bias due to recruitment into the bone lead sub-study. Results Significant effect modification was found by VDR, HMOX1, GSTP1, APOE, and AGT genetic polymorphisms when evaluated individually. Further, the bone lead-CHD associations became larger as GRS increases. After adjusting for potential confounders, a HR of CHD was 2.27 (95%CI: 1.50–3.42) with 2-fold increase in patella lead levels, among participants in the top tertile of GRS. We also detected an increasing trend in HRs across tertiles of GRS (p-trend = 0.0063). Conclusions Our findings suggest that lead-related loci as a whole may play an important role in susceptibility to lead-related CHD risk. These findings need to be validated in a separate cohort containing bone lead, lead-related genetic loci and incident CHD data. PMID:27584680

  13. Iodide-assisted total lead measurement and determination of different lead fractions in drinking water samples.

    Science.gov (United States)

    Zhang, Yuanyuan; Ng, Ding-Quan; Lin, Yi-Pin

    2012-07-01

    Lead and its compounds are toxic and can harm human health, especially the intelligence development in children. Accurate measurement of total lead present in drinking water is crucial in determining the extent of lead contamination and human exposure due to drinking water consumption. The USEPA method for total lead measurement (no. 200.8) is often used to analyze lead levels in drinking water. However, in the presence of high concentration of the tetravalent lead corrosion product PbO(2), the USEPA method was not able to fully recover particulate lead due to incomplete dissolution of PbO(2) particles during strong acid digestion. In this study, a new procedure that integrates membrane separation, iodometric PbO(2) measurement, strong acid digestion and ICP-MS measurement was proposed and evaluated for accurate total lead measurement and quantification of different lead fractions including soluble Pb(2+), particulate Pb(II) carbonate and PbO(2) in drinking water samples. The proposed procedure was evaluated using drinking water reconstituted with spiked Pb(2+), spiked particulate Pb(II) carbonate and in situ formed or spiked PbO(2). Recovery tests showed that the proposed procedure and the USEPA method can achieve 93-112% and 86-103% recoveries respectively for samples containing low PbO(2) concentrations (0.018-0.076 mg Pb per L). For samples containing higher concentrations of PbO(2) (0.089-1.316 mg Pb per L), the USEPA method failed to meet the recovery requirement for total lead (85-115%) while the proposed method can achieve satisfactory recoveries (91-111%) and differentiate the soluble Pb(2+), particulate Pb(II) carbonate and PbO(2).

  14. Anemia risk in relation to lead exposure in lead-related manufacturing.

    Science.gov (United States)

    Hsieh, Nan-Hung; Chung, Shun-Hui; Chen, Szu-Chieh; Chen, Wei-Yu; Cheng, Yi-Hsien; Lin, Yi-Jun; You, Su-Han; Liao, Chung-Min

    2017-05-05

    Lead-exposed workers may suffer adverse health effects under the currently regulated blood lead (BPb) levels. However, a probabilistic assessment about lead exposure-associated anemia risk is lacking. The goal of this study was to examine the association between lead exposure and anemia risk among factory workers in Taiwan. We first collated BPb and indicators of hematopoietic function data via health examination records that included 533 male and 218 female lead-exposed workers between 2012 and 2014. We used benchmark dose (BMD) modeling to estimate the critical effect doses for detection of abnormal indicators. A risk-based probabilistic model was used to characterize the potential hazard of lead poisoning for job-specific workers by hazard index (HI). We applied Bayesian decision analysis to determine whether BMD could be implicated as a suitable BPb standard. Our results indicated that HI for total lead-exposed workers was 0.78 (95% confidence interval: 0.50-1.26) with risk occurrence probability of 11.1%. The abnormal risk of anemia indicators for male and female workers could be reduced, respectively, by 67-77% and 86-95% by adopting the suggested BPb standards of 25 and 15 μg/dL. We conclude that cumulative exposure to lead in the workplace was significantly associated with anemia risk. This study suggests that current BPb standard needs to be better understood for the application of lead-exposed population protection in different scenarios to provide a novel standard for health management. Low-level lead exposure risk is an occupational and public health problem that should be paid more attention.

  15. Lead/acid battery technology

    Science.gov (United States)

    Manders, J. E.; Lam, L. T.; Peters, K.; Prengaman, R. D.; Valeriote, E. M.

    Following the schedule of previous Asian Battery Conferences, the Proceedings closed with an expert panel of battery scientists and technologists who answered questions put by the assembled delegates. The subjects under consideration were as follows. Grid alloys: grain structure of lead-calcium and lead-calcium-tin alloys; dross problems; control of calcium content; cast-on-strap; terminal-post attack; porosity/acid-wicking problems; effect of silver; lead-cadmium alloys. Leady oxide: α-PbO:β-PbO ratio; influence on plate-processing and battery performance. Paste-mixing and curing: influence of amorphous material. Plate formation: black/powdery plates; effect of acid concentration; charge level. Valve-regulated batteries: mass balances; grid thickness; shelf life. Battery charging: overcharge effects; fast charging; temperature effects; string configurations; sodium sulfate additive.

  16. The genetic alteration of retinoblastoma gene in esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jae Il; Shim, Yung Mok; Kim, Chang Min [Korea Cancer Center Hospital of Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1994-12-01

    Retinoblastoma(RB) gene is the prototype of tumor suppressor gene and it`s alteration have been frequently observed in a large number of human tumors. To investigate the role of RB in esophageal cancer, we studied 36 esophageal cancer tissues with Southern blot analysis to detect gross LOH and PCR-SSCP method to find minute LOH and mutation, if any. In the cases with abnormalities, the nucleotide sequence analysis was performed. Allelic loss of chromosome 13q14 occurred in 20 out of 32 informative cases (62.5%) by Southern analysis. Furthermore, PCR-LOH added three positive cases. Mobility shift by PCR-SSCP was observed in one case at exon 22, which showed 1 bp deletion in codon 771 of RB gene resulting in frame shift mutation. Besides, nine PCR-band alteration in tumor tissue compared with normal tissue were observed in exon 14 and 22, but mutation was not found on sequencing analysis suggesting the epigenetic alteration in tumor tissue. Analysis of the clinical data did not show any difference depending upon RB alteration. However, the total incidence of RB gene may play an important role in the development of esophageal cancer. The main genetic alteration of RB gene was deletion detected by Southern blot and one bp deletion leading to frame shift was also observed. 8 figs, 5 tabs. (Author).

  17. Radiation-induced epigenetic alterations after low and high LET irradiations

    International Nuclear Information System (INIS)

    Aypar, Umut; Morgan, William F.; Baulch, Janet E.

    2011-01-01

    Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding radiation-induced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET X-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NFκB), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. We demonstrate that miRNA expression levels can be altered after X-ray irradiation and that these miRNA are involved in chromatin remodeling and DNA methylation. A higher incidence of epigenetic changes was observed after exposure to X-rays than Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This distinction is apparent at miRNA analyses at which only three miRNA involved in two major pathways were altered after high LET irradiations while six miRNA involved in five major pathways were altered after low LET irradiations. This study also shows that the irradiated cells acquire epigenetic changes suggesting that epigenetic aberrations may arise in the

  18. Phytoplasmal infection derails genetically preprogrammed meristem fate and alters plant architecture.

    Science.gov (United States)

    Wei, Wei; Davis, Robert Edward; Nuss, Donald L; Zhao, Yan

    2013-11-19

    In the life cycle of higher plants, it is the fate of meristem cells that determines the pattern of growth and development, and therefore plant morphotype and fertility. Floral transition, the turning point from vegetative growth to reproductive development, is achieved via genetically programmed sequential changes in meristem fate from vegetative to inflorescence, and to floral, leading to flower formation and eventual seed production. The transition is rarely reversible once initiated. In this communication, we report that a bacterial infection can derail the genetically programmed fate of meristem cells, thereby drastically altering the growth pattern of the host plant. We identified four characteristic symptoms in tomato plants infected with a cell wall-less bacterium, phytoplasma. The symptoms are a manifestation of the pathogen-induced alterations of growth pattern, whereas each symptom corresponds to a distinct phase in the derailment of shoot apical meristem fate. The phases include premature floral meristem termination, suppressed floral meristem initiation, delayed conversion of vegetative meristem to inflorescence meristem, and repetitive initiation and outgrowth of lateral vegetative meristems. We further found that the pathogen-induced alterations of growth pattern were correlated with transcriptional reprogramming of key meristem switching genes. Our findings open an avenue toward understanding pathological alterations in patterns of plant growth and development, thus aiding identification of molecular targets for disease control and symptom alleviation. The findings also provide insights for understanding stem cell pluripotency and raise a tantalizing possibility for using phytoplasma as a tool to dissect the course of normal plant development and to modify plant morphogenesis by manipulating meristem fate.

  19. Radiation-induced epigenetic alterations after low and high LET irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Aypar, Umut, E-mail: uaypa001@umaryland.edu [Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Morgan, William F. [Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Baulch, Janet E. [Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD 21201 (United States)

    2011-02-10

    Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding radiation-induced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET X-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NF{kappa}B), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. We demonstrate that miRNA expression levels can be altered after X-ray irradiation and that these miRNA are involved in chromatin remodeling and DNA methylation. A higher incidence of epigenetic changes was observed after exposure to X-rays than Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This distinction is apparent at miRNA analyses at which only three miRNA involved in two major pathways were altered after high LET irradiations while six miRNA involved in five major pathways were altered after low LET irradiations. This study also shows that the irradiated cells acquire epigenetic changes suggesting that epigenetic aberrations may arise

  20. Leading and managing organizational change initiatives

    OpenAIRE

    Peus, Claudia; Frey, Dieter; Gerkhardt, Marit; Fischer, Peter; Traut-Mattausch, Eva

    2009-01-01

    Although indispensable for long-term economic growth, organizational changes are usually met with resistance. This article draws on psychological theories and empirical evidence to highlight why and under what conditions changes lead to resistance and what likely consequences of resistance are. Furthermore, the article discusses the variables that have been identified as success factors for organizational change initiatives. These include individual difference variables and objective characte...

  1. Oral complications of cancer therapies. Mucosal alterations

    Energy Technology Data Exchange (ETDEWEB)

    Squier, C.A. (Univ. of Iowa, Iowa City (USA))

    1990-01-01

    The initial effect of anticancer therapy, such as radiation and chemotherapy, is on the rapidly proliferating cells of the oral epithelium. As a consequence, the epithelium may show atrophy and ulceration. The sites of these alterations are related to the rate of epithelial proliferation. Regions of rapid proliferation, such as the oral lining mucosa, show a greater frequency of ulceration than masticatory mucosa or skin. Subsequent changes in the mucosa reflect damage to connective tissue, including fibroblasts and blood vessels. This results in hyalinization of collagen, hypovascularity, and ischemia. Indirect effects of anticancer therapy may include granulocytopenia and reduced salivary secretion, so that the protective mucin coating of the epithelium is compromised. These changes result in tissue with reduced barrier function and impaired ability to heal and to resist entry of pathogens, thus increasing the risk of systemic infections.

  2. Mangrove microclimates alter seedling dynamics at the range edge.

    Science.gov (United States)

    Devaney, John L; Lehmann, Michael; Feller, Ilka C; Parker, John D

    2017-10-01

    Recent climate warming has led to asynchronous species migrations, with major consequences for ecosystems worldwide. In woody communities, localized microclimates have the potential to create feedback mechanisms that can alter the rate of species range shifts attributed to macroclimate drivers alone. Mangrove encroachment into saltmarsh in many areas is driven by a reduction in freeze events, and this encroachment can further modify local climate, but the subsequent impacts on mangrove seedling dynamics are unknown. We monitored microclimate conditions beneath mangrove canopies and adjacent open saltmarsh at a freeze-sensitive mangrove-saltmarsh ecotone and assessed survival of experimentally transplanted mangrove seedlings. Mangrove canopies buffered night time cooling during the winter, leading to interspecific differences in freeze damage on mangrove seedlings. However, mangrove canopies also altered biotic interactions. Herbivore damage was higher under canopies, leading to greater mangrove seedling mortality beneath canopies relative to saltmarsh. While warming-induced expansion of mangroves can lead to positive microclimate feedbacks, simultaneous fluctuations in biotic drivers can also alter seedling dynamics. Thus, climate change can drive divergent feedback mechanisms through both abiotic and biotic channels, highlighting the importance of vegetation-microclimate interactions as important moderators of climate driven range shifts. © 2017 by the Ecological Society of America.

  3. The leaching of lead from lead-based paint in landfill environments.

    Science.gov (United States)

    Wadanambi, Lakmini; Dubey, Brajesh; Townsend, Timothy

    2008-08-30

    Lead leaching from lead-based paint (LBP) was examined using standardized laboratory protocols and tests with leachate from actual and simulated landfill environments. Two different LBP samples were tested; leaching solutions included leachates from three municipal solid waste (MSW) landfills and three construction and demolition (C&D) debris landfills. The toxicity characteristic leaching procedure (TCLP) and the synthetic precipitation leaching procedure (SPLP) were also performed. Lead concentrations were many times higher using the TCLP compared to the SPLP and the landfill leachates. No significant difference (alpha=0.05) was observed in leached lead concentrations from the MSW landfill and C&D debris landfill leachates. The impact of other building materials present in LBP debris on lead leaching was examined by testing mixtures of LBP (2%) and different building materials (98%; steel, wood, drywall, concrete). The type of substrate present impacted lead leaching results, with concrete demonstrating the most dramatic impact; the lowest lead concentrations were measured in the presence of concrete under both TCLP and SPLP extractions.

  4. A theoretical analysis of hemodynamic and biomechanical alterations in intracranial AVMs after radiosurgery

    International Nuclear Information System (INIS)

    Lo, E.H.

    1993-01-01

    Stereotactic radiosurgery is being increasingly used to treat intracranial arteriovenous malformations (AVMs). However, successful radiosurgery may involve latent periods of 1-2 years prior to AVM obliteration. This latent period include states of altered flow patterns that may not influence hemorrhage probabilities. The probability of hemorrhage is likely to be related to the degree of biomechanical stress across the AVM shunt walls. This paper describes a theoretical analysis of the altered hemodynamics and biomechanical stresses within AVM shunts post-radiosurgery. The mathematical model is comprised of linked flow compartments that represent the AVM and adjacent normal vasculature. As obliteration of the irradiated shunts occurs, changes in flow rates and pressure gradients are calculated based on first order fluid dynamics. Stress on the AVM shunt walls is calculated based on tangential forces due to intramural pressure. Two basic models are presented: a distribution of shunts with fixed thin walls subject to step-function obliteration, and a distribution of shunts subject to luminal obliteration from slowly thickening walls. Variations on these models are analyzed, including sequential, selective and random shunt obliteration, and uniform or Poisson distributions of shunt radii. Model I reveals that the range of pressure alterations in the radiosurgically-treated AVM include the possibility of transient increases in the total biomechanical stress within the shunt walls prior to obliteration. Model II demonstrates that uniform luminal narrowing via thickened walls should lead to reduced transmural stresses. The precise temporal pattern of AVM flow decrease and biomechanical stress reduction depends on the selection of shunts that are obliterated. 34 refs., 5 figs., 1 tab

  5. Spent lead-acid battery recycling in China - A review and sustainable analyses on mass flow of lead.

    Science.gov (United States)

    Sun, Zhi; Cao, Hongbin; Zhang, Xihua; Lin, Xiao; Zheng, Wenwen; Cao, Guoqing; Sun, Yong; Zhang, Yi

    2017-06-01

    Lead is classified to be one of the top heavy metal pollutants in China. The corresponding environmental issues especially during the management of spent lead-acid battery have already caused significant public awareness and concern. This research gives a brief overview on the recycling situation based on an investigation of the lead industry in China and also the development of technologies for spent lead-acid batteries. The main principles and research focuses of different technologies including pyrometallurgy, hydrometallurgy and greener technologies are summarized and compared. Subsequently, the circulability of lead based on the entire life cycle analyses of lead-acid battery is calculated. By considering different recycling schemes, the recycling situation of spent lead-acid battery in China can be understood semi-quantitatively. According to this research, 30% of the primary lead production can be shut down that the lead production can still ensure consecutive life cycle operation of lead-acid battery, if proper management of the spent lead-acid battery is implemented according to current lead industry situation in China. This research provides a methodology on the view of lead circulability in the whole life cycle of a specific product and is aiming to contribute more quantitative guidelines for efficient organization of lead industry in China. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Static, Lightweight Includes Resolution for PHP

    NARCIS (Netherlands)

    M.A. Hills (Mark); P. Klint (Paul); J.J. Vinju (Jurgen)

    2014-01-01

    htmlabstractDynamic languages include a number of features that are challenging to model properly in static analysis tools. In PHP, one of these features is the include expression, where an arbitrary expression provides the path of the file to include at runtime. In this paper we present two

  7. Article Including Environmental Barrier Coating System

    Science.gov (United States)

    Lee, Kang N. (Inventor)

    2015-01-01

    An enhanced environmental barrier coating for a silicon containing substrate. The enhanced barrier coating may include a bond coat doped with at least one of an alkali metal oxide and an alkali earth metal oxide. The enhanced barrier coating may include a composite mullite bond coat including BSAS and another distinct second phase oxide applied over said surface.

  8. Rare thoracic cancers, including peritoneum mesothelioma

    NARCIS (Netherlands)

    Siesling, Sabine; van der Zwan, Jan Maarten; Izarzugaza, Isabel; Jaal, Jana; Treasure, Tom; Foschi, Roberto; Ricardi, Umberto; Groen, Harry; Tavilla, Andrea; Ardanaz, Eva

    Rare thoracic cancers include those of the trachea, thymus and mesothelioma (including peritoneum mesothelioma). The aim of this study was to describe the incidence, prevalence and survival of rare thoracic tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002,

  9. Rare thoracic cancers, including peritoneum mesothelioma

    NARCIS (Netherlands)

    Siesling, Sabine; Zwan, J.M.V.D.; Izarzugaza, I.; Jaal, J.; Treasure, T.; Foschi, R.; Ricardi, U.; Groen, H.; Tavilla, A.; Ardanaz, E.

    2012-01-01

    Rare thoracic cancers include those of the trachea, thymus and mesothelioma (including peritoneum mesothelioma). The aim of this study was to describe the incidence, prevalence and survival of rare thoracic tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002,

  10. Recent ATLAS results on flow measurements in lead-lead and proton-lead collisions

    CERN Document Server

    Trzupek, A; The ATLAS collaboration

    2013-01-01

    A detailed measurement of the ATLAS experiment of azimuthal anizotropy in lead-lead and p-lead collisions at the LHC will be presented. Recently, the Fourier coefficients, v2-v4, of the azimuthal angle distribution of charged particles measured in the ATLAS inner detector (|eta| < 2.5) were extracted on event-by-event basis in each of 48 milion minimum-bias Pb+Pb collisions. In particular, the measurements of the vn distributions, unfolded for experimental resolution will be presented. The relationship between the shapes of the vn distributions and the collision geometry and initial-state fluctuations will be discussed. The results will be compared with theoretical calcualtions of initial-state eccentricity distributions. We will also report on a measurement of the anisotropy of charged particle flow in lead-lead collisions using multi-particle cumulant method. The transverse momentum and pseudorapidity dependence of the elliptic flow obtained from the two- and four-particle cumulants will be shown. Event-...

  11. Lead in calcium supplements (abstract)

    International Nuclear Information System (INIS)

    Rehman, S.; Khalid, N.

    2011-01-01

    Lead present in calcium supplements is of grave concern as some lead levels have been measured up to the extent of regulatory limit set by the United States. Calcium supplements inevitably get contaminated with lead as both are naturally occurring elements. Therefore, it is imperative to indicate its level in these supplements in order to create awareness among consumers. In this study, a sophisticated analytical technique, atomic absorption spectrometry was used to analyze Pb contents in 27 commonly consumed Ca supplements manufactured by different national and multinational companies. The daily intake of lead through these supplements was calculated. Only 10% of the calcium supplements analyzed met the criteria of acceptable Pb levels (1.5 mu g/daily dose) in supplements/consumer products set by the United States. It was also found that Pb intake was highest in chelated calcium supplements 28.5 mu g/daily dose, whereas lowest 0.47 mu g/daily dose through calcium supplements with vitamin D formulation. In order to validate our results from the study conducted, IAEA-certified reference material (animal bone, H-5) was analyzed for its Pb levels. The levels of Pb determined were quite in good agreement with the certified values. (author)

  12. How to lead complex situations

    DEFF Research Database (Denmark)

    Hansen, Michael Pingel

    2013-01-01

    The military leader is experiencing increasingly more complex situations, whether it is as leader in a foreign combat environment or in the home-based public administration. Complex situations like these call for a special set of managerial responses and a special way of leading organisations...

  13. OPAL Various Lead Glass Blocks

    CERN Document Server

    These lead glass blocks were part of a CERN detector called OPAL (one of the four experiments at the LEP particle detector). OPAL uses some 12 000 blocks of glass like this to measure particle energies in the electromagnetic calorimeter. This detector measured the energy deposited when electrons and photons were slowed down and stopped.

  14. Leading in a Technological Age

    Science.gov (United States)

    Yadgir, Sheri A.

    2011-01-01

    Technology is advancing more rapidly than at any time in history since the beginning of the Industrial Revolution. In fact, experts say that the world is leaving the Industrial Age of the 20th century and entering an Information Age that will lead into the future. These advances mean that important changes are being made in all areas of life--and…

  15. Influence of maternal lead ingestion on caries in rat pups.

    Science.gov (United States)

    Watson, G E; Davis, B A; Raubertas, R F; Pearson, S K; Bowen, W H

    1997-09-01

    Lead is one of the most toxic and pervasive pollutants in society, and although there has been some lowering of blood lead levels in recent years, the levels continue to be of concern for African Americans, central city residents, residents in the Northeast region of the United States, persons with low income, and those with low educational attainment. Notably, these are the persons and the region where the highest prevalence of dental caries is observed. Information relating lead toxicity to oral health is sparse, but the preponderance of epidemiological data shows a relation between lead in the environment and the prevalence of dental caries. Using our well-defined rat caries model we found that pre- and perinatal exposure to lead results in an almost 40% increase in the prevalence of caries and a decrease in stimulated parotid function of nearly 30%. Levels of lead in milk from lead-treated dams were approximately 10 times as high as the corresponding blood lead levels, suggesting that lead is being concentrated by mammary glands. These findings may help in part to explain the comparatively high levels of dental caries observed in the inner cities of the United States where exposure to lead is common. Environmental sources of lead include drinking water, lead-based paint and, to a lesser extent, automobile and industrial emissions. In humans lead is accumulated and stored in bones (half-life of approximately 62 years), and even maternal exposure to lead decades before pregnancy can subsequently result in exposure of the developing fetus to elevated levels of lead. Moreover, lead concentration in maternal blood has been shown to increase during pregnancy and lactation because of mobilization of stored lead from bone, and typically, lead is found in milk at a higher concentration than the level found in maternal plasma at the same time point.

  16. Lead induced oxidative stress: beneficial effects of Kombucha tea.

    Science.gov (United States)

    Dipti, P; Yogesh, B; Kain, A K; Pauline, T; Anju, B; Sairam, M; Singh, B; Mongia, S S; Kumar, G Ilavazhagan Devendra; Selvamurthy, W

    2003-09-01

    To evaluate the effect of oral administration of Kombucha tea (K-tea) on lead induced oxidative stress. Sprague Dawley rats were administered 1 mL of 3.8% lead acetate solution daily alone or in combination with K-tea orally for 45 d, and the antioxidant status and lipid peroxidation were evaluated. Oral administration of lead acetate to rats enhanced lipid peroxidation and release of creatine phosphokinase and decreased levels of reduced glutathione (GSH) and antioxidant enzymes (superoxide dismutase, SOD and glutathione peroxidase, GPx). Lead treatment did not alter humoral immunity, but inhibited DTH response when compared to the control. Lead administration also increased DNA fragmentation in liver. Oral administration of Kombucha tea to rats exposed to lead decreased lipid peroxidation and DNA damage with a concomitant increase in the reduced glutathione level and GPx activity. Kombucha tea supplementation relieved the lead induced immunosuppression to appreciable levels. The results suggest that K-tea has potent antioxidant and immunomodulating properties.

  17. Effects of lead on the killing mechanisms of polymorphonuclear leukocytes

    International Nuclear Information System (INIS)

    Silberstein, C.F.

    1984-01-01

    The effects of lead on the killing mechanisms of rat polymorphonuclear leukocytes (PMN) were investigated, using male Long-Evans rats exposed to 1% lead acetate in the drinking water for varying periods of time to achieve blood lead levels ranging from 20-200 μg/dl. Studies of PMN bacterial and fungal killing activity, chemotaxis and phagocytosis demonstrated that: 1) bactericidal activity of PMN from rats exposed to lead was not altered; 2) chemotactic activity remained within normal limits; 3) the phagocytic ability of the PMN also remained unaltered. In addition to these normal findings, one major abnormality was demonstrated: a significant decrease in the ability of PMN from rats exposed to lead to kill Candida albicans. This defect was not related to age or to length of exposure. It could not be produced by addition of lead to the test system in vitro. Further investigation revealed significant decreases in PMN glucose-6-phosphate dehydrogenase, catalase, and myeloperoxidase activities. These data support two possible mechanisms for the abnormal fungicidal activity of PMN from lead-exposed rats: decrease in ability to reduce oxygen to active metabolites, or reduction in myeloperoxidase activity due to diminshed synthesis of the heme moiety required for its function

  18. Prenatal arsenic exposure alters the programming of the glucocorticoid signaling system during embryonic development

    Science.gov (United States)

    Caldwell, Katharine E.; Labrecque, Matthew T.; Solomon, Benjamin R.; Ali, Abdulmehdi; Allan, Andrea M.

    2015-01-01

    The glucocorticoid system, which plays a critical role in a host of cellular functions including mood disorders and learning and memory, has been reported to be disrupted by arsenic. In previous work we have developed and characterized a prenatal moderate arsenic exposure (50 ppb) model and identified several deficits in learning and memory and mood disorders, as well as alterations within the glucocorticoid receptor signaling system in the adolescent mouse. In these present studies we assessed the effects of arsenic on the glucocorticoid receptor (GR) pathway in both the placenta and the fetal brain in response at two critical periods, embryonic days 14 and 18. The focus of these studies was on the 11β-hydroxysteroid dehydrogenase enzymes (11β-HSD1 and 11β-HSD2) which play a key role in glucorticoid synthesis, as well as the expression and set point of the GR negative feedback regulation. Negative feedback regulation is established early in development. At E14 we found arsenic exposure significantly decreased expression of both protein and message in brain of GR and the 11β-HSD1, while 11β-HSD2 enzyme protein levels were increased but mRNA levels were decreased in the brain. These changes in brain protein continued into the E18 time point, but mRNA levels were no longer significantly altered. Placental HSD11B2 mRNA was not altered by arsenic treatment but protein levels were elevated at E14. GR placental protein levels were decreased at E18 in the arsenic exposed condition. This suggests that arsenic exposure may alter GR expression levels as a consequence of a prolonged developmental imbalance between 11β-HSD1 and 11β-HSD2 protein expression despite decreased 11HSDB2 mRNA. The suppression of GR and the failure to turn down 11β-HSD2 protein expression during fetal development may lead to an altered set point for GR signaling throughout adulthood. To our knowledge, these studies are the first to demonstrate that gestational exposure to moderate levels of

  19. Identifying and managing adverse environmental health effects: 3. Lead exposure

    Science.gov (United States)

    Sanborn, Margaret D.; Abelsohn, Alan; Campbell, Monica; Weir, Erica

    2002-01-01

    LEAD LEVELS IN NORTH AMERICAN CHILDREN AND ADULTS have declined in the past 3 decades, but lead persists in the environment in lead paint, old plumbing and contaminated soil. There are also a number of occupations and hobbies that carry a high risk of lead exposure. There is no evidence for a threshold below which lead has no adverse health effects. Blood lead levels previously considered safe are now known to cause subtle, chronic health effects. The health effects of lead exposure include developmental neurotoxicity, reproductive dysfunction and toxicity to the kidneys, blood and endocrine systems. Most lead exposures are preventable, and diagnosing lead poisoning is relatively simple compared with diagnosing health effects of exposures to other environmental toxins. Accurate assessment of lead poisoning requires specific knowledge of the sources, high-risk groups and relevant laboratory tests. In this article we review the multiple, systemic toxic effects of lead and provide current information on groups at risk, prevention, diagnosis and clinical treatment. We illustrate how the CH2OPD2 mnemonic (Community, Home, Hobbies, Occupation, Personal habits, Diet and Drugs) and specific screening questions are useful tools for physicians to quickly obtain an environmental exposure history and identify patients at high risk of lead exposure. By applying effective primary prevention, case-finding and treatment interventions for lead exposure, both the individual patient and the larger community reap the benefits of better health. PMID:12041847

  20. Public Health Consequences of Lead in Drinking Water.

    Science.gov (United States)

    Levallois, Patrick; Barn, Prabjit; Valcke, Mathieu; Gauvin, Denis; Kosatsky, Tom

    2018-03-19

    Lead can enter drinking water from lead service lines and lead-containing plumbing, particularly in the presence of corrosive water. We review the current evidence on the role of drinking water as a source of lead exposure and its potential impacts on health, with an emphasis on children. Drinking water guidelines and mitigation strategies are also presented. The impact of lead on neurodevelopmental effects in children even at low levels of exposure is well established. Population and toxicokinetic modeling studies have found a clear relationship between water lead levels and blood lead levels in children at low levels of lead in drinking water. Various mitigation strategies can lower lead levels in water. The importance of drinking water as a contributor to total lead exposure depends on water lead levels and the amount consumed, as well as the relative contribution of other sources. Efforts should be made to reduce lead exposure for all sources, including drinking water, considering that no threshold level of exposure exists for the neurodevelopmental effects of lead in children.

  1. 77 FR 1073 - Privacy Act of 1974; Report of an Altered System of Records, Including Addition of Routine Uses...

    Science.gov (United States)

    2012-01-09

    ... supports an application for a research or marketing permit for an FDA-regulated product. Records contain... records to perform services for FDA; and individual research subjects. DATES: This notice will be.../ Agencies; international organizations; and non-governmental regulatory bodies of a foreign country. Such...

  2. Methamphetamine Alters Brain Structures, Impairs Mental Flexibility

    Science.gov (United States)

    ... Methamphetamine Alters Brain Structures, Impairs Mental Flexibility Email Facebook Twitter March 20, 2014 A new study adds to the copious existing evidence that chronic exposure to addictive drugs alters the brain in ways that make ...

  3. Lead free solder mechanics and reliability

    CERN Document Server

    Pang, John Hock Lye

    2012-01-01

    Lead-free solders are used extensively as interconnection materials in electronic assemblies and play a critical role in the global semiconductor packaging and electronics manufacturing industry. Electronic products such as smart phones, notebooks and high performance computers rely on lead-free solder joints to connect IC chip components to printed circuit boards. Lead Free Solder: Mechanics and Reliability provides in-depth design knowledge on lead-free solder elastic-plastic-creep and strain-rate dependent deformation behavior and its application in failure assessment of solder joint reliability. It includes coverage of advanced mechanics of materials theory and experiments, mechanical properties of solder and solder joint specimens, constitutive models for solder deformation behavior; numerical modeling and simulation of solder joint failure subject to thermal cycling, mechanical bending fatigue, vibration fatigue and board-level drop impact tests. This book also: Discusses the mechanical prope...

  4. Lead and Drinking Water from Private Wells

    Science.gov (United States)

    ... type=”submit” value=”Submit” /> Healthy Water Home Lead and Drinking Water from Private Wells Recommend on ... remove lead from my drinking water? What is lead? Lead is a naturally occurring bluish-gray metal ...

  5. Pregnancy increases mobilisation of lead from maternal skeleton

    International Nuclear Information System (INIS)

    Gulson, B.L.

    2000-01-01

    Lead is a neurotoxin that, even at low levels, is considered to result in neurobehavioural disorders such as cognitive deficits, learning disability and behavioural disturbances. The most recent study of Needleman et al. suggested an association between bone lead levels and antisocial and delinquent behaviour (Needleman et al., 1996). Although the neurobehavioural deficits associated with low-level lead exposure are best documented for early childhood exposures, the effects of lead on the developing nervous system are of concern. Lead readily crosses the placenta (Barltrop, 1969; Silbergeld, 1991) and changes in maternal blood lead potentially result in alterations to foetal exposure. Mobilisation of lead from body stores accumulated prior to pregnancy has been established in experimental animals (Buchet, 1977; Keller and Doherty, 1980). The cohort was to consist of 100 immigrants anticipated to provide 20 pregnant subjects who would be compared with two groups of control subjects: a matched immigrant nonpregnant control group and second-generation Australian pregnant controls. The pregnant subject also serves as her own control for a comparison of changes during pregnancy with those prior to conception. High precision lead isotopic compositions and lead concentrations were measured on: maternal blood and urine prenatally, monthly during pregnancy and post-pregnancy for 6 months; infant blood and urine for 6 months; and environmental measures sampled quarterly for 6-day duplicate diet, house dust and water, urban air and petrol. Results of this study confirm that lead is mobilised from skeletal stores at an accelerated rate during pregnancy and transferred to the foetus. This has implications for interpretations of neurobehavioural disorders attributed solely to post-natal exposure

  6. Obesity Promotes Alterations in Iron Recycling

    Directory of Open Access Journals (Sweden)

    Marta Citelli

    2015-01-01

    Full Text Available Hepcidin is a key hormone that induces the degradation of ferroportin (FPN, a protein that exports iron from reticuloendothelial macrophages and enterocytes. The aim of the present study was to experimentally evaluate if the obesity induced by a high-fat diet (HFD modifies the expression of FPN in macrophages and enterocytes, thus altering the iron bioavailability. In order to directly examine changes associated with iron metabolism in vivo, C57BL/6J mice were fed either a control or a HFD. Serum leptin levels were evaluated. The hepcidin, divalent metal transporter-1 (DMT1, FPN and ferritin genes were analyzed by real-time polymerase chain reaction. The amount of iron present in both the liver and spleen was determined by flame atomic absorption spectrometry. Ferroportin localization within reticuloendothelial macrophages was observed by immunofluorescence microscopy. Obese animals were found to exhibit increased hepcidin gene expression, while iron accumulated in the spleen and liver. They also exhibited changes in the sublocation of splenic cellular FPN and a reduction in the FPN expression in the liver and the spleen, while no changes were observed in enterocytes. Possible explanations for the increased hepcidin expression observed in HFD animals may include: increased leptin levels, the liver iron accumulation or endoplasmic reticulum (ER stress. Together, the results indicated that obesity promotes changes in iron bioavailability, since it altered the iron recycling function.

  7. Wound trauma alters ionizing radiation dose assessment

    Directory of Open Access Journals (Sweden)

    Kiang Juliann G

    2012-06-01

    Full Text Available Abstract Background Wounding following whole-body γ-irradiation (radiation combined injury, RCI increases mortality. Wounding-induced increases in radiation mortality are triggered by sustained activation of inducible nitric oxide synthase pathways, persistent alteration of cytokine homeostasis, and increased susceptibility to bacterial infection. Among these factors, cytokines along with other biomarkers have been adopted for biodosimetric evaluation and assessment of radiation dose and injury. Therefore, wounding could complicate biodosimetric assessments. Results In this report, such confounding effects were addressed. Mice were given 60Co γ-photon radiation followed by skin wounding. Wound trauma exacerbated radiation-induced mortality, body-weight loss, and wound healing. Analyses of DNA damage in bone-marrow cells and peripheral blood mononuclear cells (PBMCs, changes in hematology and cytokine profiles, and fundamental clinical signs were evaluated. Early biomarkers (1 d after RCI vs. irradiation alone included significant decreases in survivin expression in bone marrow cells, enhanced increases in γ-H2AX formation in Lin+ bone marrow cells, enhanced increases in IL-1β, IL-6, IL-8, and G-CSF concentrations in blood, and concomitant decreases in γ-H2AX formation in PBMCs and decreases in numbers of splenocytes, lymphocytes, and neutrophils. Intermediate biomarkers (7 – 10 d after RCI included continuously decreased γ-H2AX formation in PBMC and enhanced increases in IL-1β, IL-6, IL-8, and G-CSF concentrations in blood. The clinical signs evaluated after RCI were increased water consumption, decreased body weight, and decreased wound healing rate and survival rate. Late clinical signs (30 d after RCI included poor survival and wound healing. Conclusion Results suggest that confounding factors such as wounding alters ionizing radiation dose assessment and agents inhibiting these responses may prove therapeutic for radiation combined

  8. Composite Pressure Vessel Including Crack Arresting Barrier

    Science.gov (United States)

    DeLay, Thomas K. (Inventor)

    2013-01-01

    A pressure vessel includes a ported fitting having an annular flange formed on an end thereof and a tank that envelopes the annular flange. A crack arresting barrier is bonded to and forming a lining of the tank within the outer surface thereof. The crack arresting barrier includes a cured resin having a post-curing ductility rating of at least approximately 60% through the cured resin, and further includes randomly-oriented fibers positioned in and throughout the cured resin.

  9. Evaluation of home lead remediation in an Australian mining community.

    Science.gov (United States)

    Boreland, F; Lesjak, M; Lyle, D

    2009-12-20

    In 1994 a comprehensive program was established to reduce children's blood lead levels in Broken Hill, NSW, Australia. Home remediation (abatement of lead hazards in a child's home) was included as part of a case management strategy for children with blood lead levels >or=15 microg/dL. Children with blood lead levels >or=30 microg/dL were offered immediate home remediation. Children with blood lead levels of 15-29 microg/dL were allocated to 'immediate' or 'delayed' home remediation; a subset of these participated in a randomized controlled trial (RCT) to evaluate the effectiveness of home remediation for reducing blood lead levels. One hundred and seventeen children received home remediation. One hundred and thirteen returned for follow-up blood tests, 88 of whom participated in the RCT. On average children's blood lead levels decreased by 1.7 microg/dL (10%) in the 6 months after remediation and by 2.2 microg/dL (13%) in the 6-12 months after remediation. However, remediation did not significantly change the rate of decline in blood lead levels (P=0.609). There was no evidence of association between change in children's blood lead levels and changes in lead loading in their homes. The results are consistent with the published literature, which suggests that home remediation does not reduce children's exposure to lead sufficiently to cause a moderate or greater decrease in their blood lead level. In communities where lead is widely dispersed, the study suggests that it is important to assess potential sources and pathways by which children are exposed to lead when developing an intervention plan, and the need for multiple interventions to effectively reduce blood lead levels. The findings reinforce the ongoing need for rigorous epidemiological evaluation of lead management programs to improve the evidence base, and for effective primary prevention to avoid children being exposed to lead in the first place.

  10. Including Organizational Cultural Parameters in Work Processes

    National Research Council Canada - National Science Library

    Handley, Holly A; Heacox, Nancy J

    2004-01-01

    .... In order to represent the organizational impact on the work process, five organizational cultural parameters were identified and included in an algorithm for modeling and simulation of cultural...

  11. Haemophilus influenzae Disease (Including Hib) Symptoms

    Science.gov (United States)

    ... Links Global Hib Vaccination Hib Vaccination Meningitis Pneumonia Sepsis ... Haemophilus influenzae , including H. influenzae type b or Hib, can cause many different kinds of infections . Symptoms depend on ...

  12. Altered Neutrophil Function in Localized Juvenile Periodontitis: Intrinsic or Induced?

    Science.gov (United States)

    Agarwal, Sudha; Huang, Jian Ping; Piesco, Nicholas P; Suzuki, Jon B; Riccelli, Angelina E; Johns, Lee P

    1996-03-01

    Localized juvenile periodontitis (LJP) is an aggressive periodontal disease of familial nature. Neutrophils from a majority of patients with this disease exhibit decreased Chemotaxis with increased adherence, oxidative burst, and degranulation in response to opsonized bacteria. It is proposed that the biological basis for these altered neutrophil functions in LJP may be due either to intrinsic cell abnormalities or to the effect of factors present in the sera of LJP patients, which can modulate neutrophil functions. LJP neutrophils exhibit a lower number of receptors for chemoattractants and GP-110 molecules which are known to facilitate Chemotaxis. Furthermore, these cells exhibit lower signal transduction in response to a biological stimulus. These observations suggest that intrinsic cellular defects may be responsible for altered neutrophil functions in LJP. However, healthy neutrophils, when treated with very low concentrations of proinflammatory cytokines, also exhibit the characteristics of altered or "defective" LJP neutrophils. Additionally, healthy neutrophils, when treated with LJP serum, also exhibit many of the characteristics associated with LJP neutrophils. Attempts to identify these factors have shown that cytokines like TNF-α and/or IL1 β in LJP sera may be at least partially responsible for modulating neutrophil functions in LJP. These cytokines are primarily produced by activated macrophages, indicating a role for these cells in the etiology of LJP. The hyper-responsiveness of these cells to an immunologic challenge can result in local increases in cytokines leading to excessive bone loss and tissue damage at the site of infection, while systemic elevations in cytokines would lead to decreased neutrophil Chemotaxis, both of which are observed in LJP. Present evidence indicates that neutrophil functions are indeed altered in the majority of LJP patients. However, the biological basis for the alteration may not be due to the neutrophils themselves

  13. Heavy metals and epigenetic alterations in brain tumors.

    Science.gov (United States)

    Caffo, Maria; Caruso, Gerardo; Fata, Giuseppe La; Barresi, Valeria; Visalli, Maria; Venza, Mario; Venza, Isabella

    2014-12-01

    Heavy metals and their derivatives can cause various diseases. Numerous studies have evaluated the possible link between exposure to heavy metals and various cancers. Recent data show a correlation between heavy metals and aberration of genetic and epigenetic patterns. From a literature search we noticed few experimental and epidemiological studies that evaluate a possible correlation between heavy metals and brain tumors. Gliomas arise due to genetic and epigenetic alterations of glial cells. Changes in gene expression result in the alteration of the cellular division process. Epigenetic alterations in brain tumors include the hypermethylation of CpG group, hypomethylation of specific genes, aberrant activation of genes, and changes in the position of various histones. Heavy metals are capable of generating reactive oxygen assumes that key functions in various pathological mechanisms. Alteration of homeostasis of metals could cause the overproduction of reactive oxygen species and induce DNA damage, lipid peroxidation, and alteration of proteins. In this study we summarize the possible correlation between heavy metals, epigenetic alterations and brain tumors. We report, moreover, the review of relevant literature.

  14. Inline CBET Model Including SRS Backscatter

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, David S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-06-26

    Cross-beam energy transfer (CBET) has been used as a tool on the National Ignition Facility (NIF) since the first energetics experiments in 2009 to control the energy deposition in ignition hohlraums and tune the implosion symmetry. As large amounts of power are transferred between laser beams at the entrance holes of NIF hohlraums, the presence of many overlapping beat waves can lead to stochastic ion heating in the regions where laser beams overlap [P. Michel et al., Phys. Rev. Lett. 109, 195004 (2012)]. Using the CBET gains derived in this paper, we show how to implement these equations in a ray-based laser source for a rad-hydro code.

  15. Leading hadron production at HERA

    International Nuclear Information System (INIS)

    Buniatyan, A.

    2013-01-01

    Data from the recent measurements of very forward baryon and photon production with the H1 and ZEUS detectors at electron-proton collider HERA are presented and compared to the theoretical calculations and Monte Carlo models. Results are presented of the production of leading protons, neutrons and photons in deep inelastic scattering (ep → e' pX, ep → e'nX, ep → e' γ X) as well as the leading neutron production in the photoproduction of di-jets (ep → ejjXn). The forward baryon and photon results from the H1 and ZEUS Experiments are compared also with the models of the hadronic interactions of high energy Cosmic Rays. The sensitivity of the HERA data to the differences between the models is demonstrated. (authors)

  16. [Evaluation of the potential risk of perinatal exposure to lead in the Valle de Mexico].

    Science.gov (United States)

    Rothenberg, S J; Schnaas-arrieta, L; Perez-guerrero, I A; Fernandez-alba, J; Karchmer, S

    1989-01-01

    Lead exposure even at low levels has adverse effects for the central nervous system (CNS), but pregnant women, neonates, lactating infants, and preschool and school age children are most susceptible to it. In rats anatomical alterations included swelling in the mitochondria of renal duct cells (at 26 mcg/dl); biochemical effects involved marked reduction of cytochrome content in the cerebral cortex (36 mcg/dl); and physiological effects were induced at the level of 30-50 mcg/dl. Central nervous system effects entailed persistent decrease of visual acuity (65 mcg/dl at birth and 7 mcg/dl 90 days later), the increase of the latency of primary and secondary components of evoked visual responses during the prenatal and adult period (65 mcg/dl and 7 mcg/dl on days 21 and 90 after birth, respectively). 30 and even 20 mcg/dl of lead in the blood produced nerve conductivity deficits. A study of 425 children with lead poisoning showed a 39% rate of mental retardation and convulsions impervious to treatment. Lead levels within a range of 10-25 mcg/dl reduced the score on the mental development inventory by 4-8 points. The population of the Valley of Mexico numbers 15-20 million with 50% of Mexico's industry. A who investigation indicated blood levels of an average of 22.5 mcg/dl in a group of school teachers, the highest in 10 major population centers in the world. Blood levels in 405 pregnant women in Mexico City averaged 20.3 mcg/dl, and the sample from the umbilical cord of fetuses showed 13.6 mcg/dl. Another study disclosed blood levels of 16 mcg/dl in mothers and 13 mcg/dl in their offspring. The most probable sources of lead are: leaded gasoline, secondary recapture of lead for making batteries, use of paints, ceramics used for storing and cooking food, lead seal of milk containers, and consumption of food contaminated with lead.

  17. Lead and cadmium in food

    International Nuclear Information System (INIS)

    Gliesmann, S.; Kruse, H.; Kriews, M.; Mangels, H.

    1992-08-01

    The amounts of lead and cadmium produced and processed in these days are considerable. As a result, our environment is increasingly polluted by heavy metals and industrial installations, motor vehicles or incinerating plants appear to be among the main culprits here. Air and water are the media permitting the entry of heavy metals into our natural environment where they accumulate in the soil and then gradually migrate into the plants. Their further transport in the food constitutes the third step in the environmental spread of heavy metals. The consumption of muscle and organ meats, of vegetables, fruits, canned food and drinking water is unavoidably associated with some ingestion of lead and cadmium. The degree to which they are taken up and stored in different tissues is determined by absorption properties and the nutritional state of the organism. Cadmium tends to accumulate in the kidneys, lead is mainly stored in the bones. A continuously increasing uptake finally results in health injuries that range from unspecific complaints to damaged kidneys or bones and disorders of liver function. Children and elderly people are at a particular risk here. The level of food contamination is such that screening for heavy metals must be rigorously carried out once appropriate legal thresholds have been set, which ought to be based on proven detrimental effects of lead and cadmium on our health and also take account of infants and children or any other risk groups, where particular caution must be exercised. It should be pointed out that such thresholds have so far not been determined. (orig./MG) [de

  18. Leading Indian Business-Groups

    Directory of Open Access Journals (Sweden)

    Maria Alexandrovna Vorobyeva

    2016-01-01

    Full Text Available The goal of this paper is to investigate the evolution of the leading Indian business-groups under the conditions of economical liberalization. It is shown that the role of modern business-groups in the Indian economy is determined by their high rate in the gross domestic product (GDP, huge overall actives, substantial pert in the e[port of goods and services, as well as by their activities in modern branch structure formatting, and developing labor-intensive and high-tech branches. They strongly influence upon economical national strategies, they became a locomotive of internationalization and of transnationalization of India, the basis of the external economy factor system, the promoters of Indian "economical miracle" on the world scene, and the dynamical segment of economical and social development of modern India. The tendencies of the development of the leading Indian business groups are: gradual concentration of production in few clue sectors, "horizontal" structure, incorporation of the enterprises into joint-stock structure, attraction of hired top-managers and transnationaliziation. But against this background the leading Indian business-groups keep main traditional peculiarities: they mostly still belong to the families of their founders, even today they observe caste or communal relations which are the basis of their non-formal backbone tides, they still remain highly diversificated structures with weak interrelations. Specific national ambivalence and combination of traditions and innovations of the leading Indian business-groups provide their high vitality and stability in the controversial, multiform, overloaded with caste and confessional remains Indian reality. We conclude that in contrast to the dominant opinion transformation of these groups into multisectoral corporations of the western type is far from completion, and in the nearest perspective they will still possess all their peculiarities and incident social and economical

  19. Leading Edge Device Aerodynamic Optimization

    Directory of Open Access Journals (Sweden)

    Marius Gabriel COJOCARU

    2015-12-01

    Full Text Available Leading edge devices are conventionally used as aerodynamic devices that enhance performances during landing and in some cases during takeoff. The need to increase the efficiency of the aircrafts has brought the idea of maintaining as much as possible a laminar flow over the wings. This is possible only when the leading edge of the wings is free from contamination, therefore using the leading edge devices with the additional role of shielding during takeoff. Such a device based on the Krueger flap design is aerodynamically analyzed and optimized. The optimization comprises three steps: first, the positioning of the flap such that the shielding criterion is kept, second, the analysis of the flap size and third, the optimization of the flap shape. The first step is subject of a gradient based optimization process of the position described by two parameters, the position along the line and the deflection angle. For the third step the Adjoint method is used to gain insight on the shape of the Krueger flap that will extend the most the stall limit. All these steps have been numerically performed using Ansys Fluent and the results are presented for the optimized shape in comparison with the baseline configuration.

  20. Mortality of lead smelter workers

    Energy Technology Data Exchange (ETDEWEB)

    Selevan, S.G.; Landrigan, P.J.; Stern, F.B.; Jones, J.H.

    1985-10-01

    To examine patterns of death in lead smelter workers, a retrospective analysis of mortality was conducted in a cohort of 1,987 males employed between 1940 and 1965 at a primary lead smelter in Idaho. Overall mortality was similar to that of the United States white male population (standardized mortality ratio (SMR) = 98). Excess mortality, however, was found from chronic renal disease (SMR = 192; confidence interval (CI) = 88-364), and the risk of death from renal disease increased with increasing duration of employment, such that after 20 years employment, the standardized mortality ratio reached 392 (CI = 107-1,004). Excess mortality was also noted for nonmalignant respiratory disease (SMR = 187, CI = 128-264). Eight of 32 deaths in this category were caused by silicosis; at least five workers who died of silicosis had been miners for a part of their lives. An additional 11 deaths resulted from tuberculosis (SMR = 139; CI = 69-249); in six of these cases, silicosis was a contributory cause of death. Cancer mortality was not increased overall (SMR = 95; CI = 78-114). An increase, however, was noted for deaths from kidney cancer (six cases; SMR = 204; CI = 75-444). Finally, excess mortality was noted for injuries (SMR = 138; CI = 104-179); 13 (23%) of the 56 deaths in this category were caused by mining injuries. The data from this study are consistent with previous reports of increased mortality from chronic renal disease in persons exposed occupationally to lead.

  1. Loss of a single allele for Ku80 leads to progenitor dysfunction and accelerated aging in skeletal muscle

    Science.gov (United States)

    Didier, Nathalie; Hourdé, Christophe; Amthor, Helge; Marazzi, Giovanna; Sassoon, David

    2012-01-01

    Muscle wasting is a major cause of morbidity in the elderly. Ku80 is required for DNA double strand repair and is implicated in telomere maintenance. Complete loss-of-function leads to reduced post-natal growth and severe progeria in mice. We examined the role of Ku80 in age-related skeletal muscle atrophy. While complete loss of Ku80 leads to pronounced aging in muscle as expected, accompanied by accumulation of DNA damage, loss of a single allele is sufficient to accelerate aging in skeletal muscle although post-natal growth is normal. Ku80 heterozygous muscle shows no DNA damage accumulation but undergoes premature telomere shortening that alters stem cell self-renewal through stress response pathways including p53. These data reveal an unexpected requirement for both Ku80 alleles for optimal progenitor function and prevention of early onset aging in muscle, as well as providing a useful model for therapeutic approaches. PMID:22915554

  2. When good news leads to bad choices.

    Science.gov (United States)

    McDevitt, Margaret A; Dunn, Roger M; Spetch, Marcia L; Ludvig, Elliot A

    2016-01-01

    Pigeons and other animals sometimes deviate from optimal choice behavior when given informative signals for delayed outcomes. For example, when pigeons are given a choice between an alternative that always leads to food after a delay and an alternative that leads to food only half of the time after a delay, preference changes dramatically depending on whether the stimuli during the delays are correlated with (signal) the outcomes or not. With signaled outcomes, pigeons show a much greater preference for the suboptimal alternative than with unsignaled outcomes. Key variables and research findings related to this phenomenon are reviewed, including the effects of durations of the choice and delay periods, probability of reinforcement, and gaps in the signal. We interpret the available evidence as reflecting a preference induced by signals for good news in a context of uncertainty. Other explanations are briefly summarized and compared. © 2016 Society for the Experimental Analysis of Behavior.

  3. Lead stress effects on physiobiochemical activities of higher plants.

    Science.gov (United States)

    Sengar, Rakesh Singh; Gautam, Madhu; Sengar, Rajesh Singh; Garg, Sanjay Kumar; Sengar, Kalpana; Chaudhary, Reshu

    2008-01-01

    Lead is a metallic pollutant emanating from various environmental sources including industrial wastes, combustion of fossil fuels, and use of agrochemicals. Lead may exist in the atmosphere as dusts, fumes, mists, and vapors, and in soil as a mineral. Soils along roadsides are rich in lead because vehicles burn leaded gasoline, which contributes to environmental lead pollution. Other important sources of lead pollution are geological weathering, industrial processing of ores and minerals, leaching of lead from solid wastes, and animal and human excreta. Lead is nondegradable, readily enters the food chain, and can subsequently endanger human and animal health. Lead is one of the most important environment pollutants and deserves the increasing attention it has received in recent decades. The present effort was undertaken to review lead stress effects on the physiobiochemical activity of higher plants. Lead has gained considerable attention as a potent heavy metal pollutant because of growing anthropogenic pressure on the environment. Lead-contaminated soils show a sharp decline in crop productivity. Lead is absorbed by plants mainly through the root system and in minor amounts through the leaves. Within the plants, lead accumulates primarily in roots, but some is translocated to aerial plant parts. Soil pH, soil particle size, cation-exchange capacity, as well as root surface area, root exudation, and mycorrhizal transpiration rate affect the availability and uptake of lead by plants. Only a limited amount of lead is translocated from roots to other organs because there are natural plant barriers in the root endodermis. At lethal concentrations, this barrier is broken and lead may enter vascular tissues. Lead in plants may form deposits of various sizes, present mainly in intercellular spaces, cell walls, and vacuoles. Small deposits of this metal are also seen in the endoplasmic reticulum, dictyosome, and dictyosome-derived vesicles. After entering the cells, lead

  4. Challenges and opportunities for managing aquatic mercury pollution in altered landscapes.

    Science.gov (United States)

    Hsu-Kim, Heileen; Eckley, Chris S; Achá, Dario; Feng, Xinbin; Gilmour, Cynthia C; Jonsson, Sofi; Mitchell, Carl P J

    2018-03-01

    The environmental cycling of mercury (Hg) can be affected by natural and anthropogenic perturbations. Of particular concern is how these disruptions increase mobilization of Hg from sites and alter the formation of monomethylmercury (MeHg), a bioaccumulative form of Hg for humans and wildlife. The scientific community has made significant advances in recent years in understanding the processes contributing to the risk of MeHg in the environment. The objective of this paper is to synthesize the scientific understanding of how Hg cycling in the aquatic environment is influenced by landscape perturbations at the local scale, perturbations that include watershed loadings, deforestation, reservoir and wetland creation, rice production, urbanization, mining and industrial point source pollution, and remediation. We focus on the major challenges associated with each type of alteration, as well as management opportunities that could lessen both MeHg levels in biota and exposure to humans. For example, our understanding of approximate response times to changes in Hg inputs from various sources or landscape alterations could lead to policies that prioritize the avoidance of certain activities in the most vulnerable systems and sequestration of Hg in deep soil and sediment pools. The remediation of Hg pollution from historical mining and other industries is shifting towards in situ technologies that could be less disruptive and less costly than conventional approaches. Contemporary artisanal gold mining has well-documented impacts with respect to Hg; however, significant social and political challenges remain in implementing effective policies to minimize Hg use. Much remains to be learned as we strive towards the meaningful application of our understanding for stakeholders, including communities living near Hg-polluted sites, environmental policy makers, and scientists and engineers tasked with developing watershed management solutions. Site-specific assessments of Me

  5. A Case for Microtubule Vulnerability in Amyotrophic Lateral Sclerosis: Altered Dynamics During Disease

    Directory of Open Access Journals (Sweden)

    Jayden A Clark

    2016-09-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is an aggressive multifactorial disease converging on a common pathology: the degeneration of motor neurons, their axons and neuromuscular synapses. This vulnerability and dysfunction of motor neurons highlights the dependency of these large cells on their intracellular machinery. Neuronal microtubules are an intracellular structure that facilitates a myriad of vital neuronal functions, including activity dependent axonal transport. In ALS it is becoming increasingly apparent that microtubules are likely to be a critical component of this disease. Not only are disruptions in this intracellular machinery present in the vast majority of seemingly sporadic cases, recent research has revealed that mutation to a microtubule protein, the tubulin isoform TUBA4A, is sufficient to cause a familial, albeit rare, form of disease. In both sporadic and familial disease, studies have provided evidence that microtubule mediated deficits in axonal transport are the tipping point for motor neuron survivability. Axonal transport deficits would lead to abnormal mitochondrial recycling, decreased vesicle and mRNA transport and limited signalling of key survival factors from the neurons peripheral synapses, causing the characteristic peripheral ‘die back’. This disruption to microtubule dependant transport in ALS has been shown to result from alterations in the phenomenon of microtubule dynamic instability: the rapid growth and shrinkage of microtubule polymers. This is accomplished primarily due to aberrant alterations to microtubule associated proteins (MAPS that regulate microtubule stability. Indeed, the current literature would argue that microtubule stability, particularly alterations in their dynamics, may be the initial driving force behind many familial and sporadic insults in ALS. Pharmacological stabilisation of the microtubule network offers an attractive therapeutic strategy in ALS; indeed it has shown promise in

  6. Alterations in audiovisual simultaneity perception in amblyopia.

    Science.gov (United States)

    Richards, Michael D; Goltz, Herbert C; Wong, Agnes M F

    2017-01-01

    Amblyopia is a developmental visual impairment that is increasingly recognized to affect higher-level perceptual and multisensory processes. To further investigate the audiovisual (AV) perceptual impairments associated with this condition, we characterized the temporal interval in which asynchronous auditory and visual stimuli are perceived as simultaneous 50% of the time (i.e., the AV simultaneity window). Adults with unilateral amblyopia (n = 17) and visually normal controls (n = 17) judged the simultaneity of a flash and a click presented with both eyes viewing. The signal onset asynchrony (SOA) varied from 0 ms to 450 ms for auditory-lead and visual-lead conditions. A subset of participants with amblyopia (n = 6) was tested monocularly. Compared to the control group, the auditory-lead side of the AV simultaneity window was widened by 48 ms (36%; p = 0.002), whereas that of the visual-lead side was widened by 86 ms (37%; p = 0.02). The overall mean window width was 500 ms, compared to 366 ms among controls (37% wider; p = 0.002). Among participants with amblyopia, the simultaneity window parameters were unchanged by viewing condition, but subgroup analysis revealed differential effects on the parameters by amblyopia severity, etiology, and foveal suppression status. Possible mechanisms to explain these findings include visual temporal uncertainty, interocular perceptual latency asymmetry, and disruption of normal developmental tuning of sensitivity to audiovisual asynchrony.

  7. Investigation and assessment of lead slag concrete as nuclear shields

    International Nuclear Information System (INIS)

    Zaghloul, Y.R.

    2009-01-01

    The present work is concerned with the efficiency of heavy weight concrete as a shielding material in constructing nuclear installations as well as for radioactive wastes disposal facilities.In this context, lead slag was used as a replacement for fine aggregates in heavy concrete shields that include local heavy weight aggregates (namely; barite and ilmenite) as well as normal concrete includes dolomite and sand as coarse and fine aggregates, as a reference. The effect of different percentages of lead slag was investigated to assess the produced lead slag concrete as a nuclear shielding material. The different properties (physical, mechanical and nuclear) of the produced lead slag concrete were investigated. The results obtained showed that increasing the lead slag percentage improving the investigated properties of the different concrete mixes. In addition, ilmenite concrete with 20% lead slag showed the best results for all the investigated properties.

  8. Altering the Balance between Excitation and Inhibition in Cultured Neural Networks

    Science.gov (United States)

    Dzakpasu, Rhonda

    2010-03-01

    How is the network temporal structure altered when the balance between excitation and inhibition is changed? Proper balance is essential for normal brain function, including cognitive processing, the representation of sensory information and motor control. When the balance is compromised, neurological disorders may result. We use a simple reduced experimental system to investigate how manipulating the number of inhibitory neurons in a network of cultured hippocampal neurons affects synchronized bursting activity, the most prominent temporal signature of cultured hippocampal networks. Inhibitory neurons are thought to control spike timing and modulate network excitability and their absence may lead to widespread synchronization. We culture dissociated hippocampal neurons with varying quantities of inhibitory neurons on an 8x8 grid of extracellular electrodes and study how inhibitory neurons modulate network temporal dynamics. We show that as the proportion of inhibitory neurons increase, there is a dramatic transition in the temporal pattern.

  9. Estrogen mediates innate and adaptive immune alterations to influenza infection in pregnant mice.

    Directory of Open Access Journals (Sweden)

    Michael A Pazos

    Full Text Available Pregnancy is a leading risk factor for severe complications during an influenza virus infection. Women infected during their second and third trimesters are at increased risk for severe cardiopulmonary complications, premature delivery, and death. Here, we establish a murine model of aerosolized influenza infection during pregnancy. We find significantly altered innate antiviral responses in pregnant mice, including decreased levels of IFN-β, IL-1α, and IFN-γ at early time points of infection. We also find reduced cytotoxic T cell activity and delayed viral clearance. We further demonstrate that pregnancy levels of the estrogen 17-β-estradiol are able to induce key anti-inflammatory phenotypes in immune responses to the virus independently of other hormones or pregnancy-related stressors. We conclude that elevated estrogen levels result in an attenuated anti-viral immune response, and that pregnancy-associated morbidities occur in the context of this anti-inflammatory phenotype.

  10. Estrogen mediates innate and adaptive immune alterations to influenza infection in pregnant mice.

    Science.gov (United States)

    Pazos, Michael A; Kraus, Thomas A; Muñoz-Fontela, César; Moran, Thomas M

    2012-01-01

    Pregnancy is a leading risk factor for severe complications during an influenza virus infection. Women infected during their second and third trimesters are at increased risk for severe cardiopulmonary complications, premature delivery, and death. Here, we establish a murine model of aerosolized influenza infection during pregnancy. We find significantly altered innate antiviral responses in pregnant mice, including decreased levels of IFN-β, IL-1α, and IFN-γ at early time points of infection. We also find reduced cytotoxic T cell activity and delayed viral clearance. We further demonstrate that pregnancy levels of the estrogen 17-β-estradiol are able to induce key anti-inflammatory phenotypes in immune responses to the virus independently of other hormones or pregnancy-related stressors. We conclude that elevated estrogen levels result in an attenuated anti-viral immune response, and that pregnancy-associated morbidities occur in the context of this anti-inflammatory phenotype.

  11. DNA methylation alterations in Alzheimer's disease.

    Science.gov (United States)

    Yokoyama, Amy S; Rutledge, John C; Medici, Valentina

    2017-05-01

    The observation that Alzheimer's disease (AD) patients with similar and even identical genetic backgrounds often present with heterogeneous pathologies has prompted the hypothesis that epigenetics may contribute to AD. While the study of epigenetics encompasses a variety of modifications including histone modifications and non-coding RNAs, much of the research on how epigenetics might impact AD pathology has been focused on DNA methylation. To this end, several studies have characterized DNA methylation alterations in various brain regions of individuals with AD, with conflicting results. This review examines the results of studies analyzing both global and gene-specific DNA methylation changes in AD and also assesses the results of studies analyzing DNA hydroxymethylation in patients with AD.

  12. Epigenetic alterations underlying autoimmune diseases.

    Science.gov (United States)

    Aslani, Saeed; Mahmoudi, Mahdi; Karami, Jafar; Jamshidi, Ahmad Reza; Malekshahi, Zahra; Nicknam, Mohammad Hossein

    2016-01-01

    Recent breakthroughs in genetic explorations have extended our understanding through discovery of genetic patterns subjected to autoimmune diseases (AID). Genetics, on the contrary, has not answered all the conundrums to describe a comprehensive explanation of causal mechanisms of disease etiopathology with regard to the function of environment, sex, or aging. The other side of the coin, epigenetics which is defined by gene manifestation modification without DNA sequence alteration, reportedly has come in to provide new insights towards disease apprehension through bridging the genetics and environmental factors. New investigations in genetic and environmental contributing factors for autoimmunity provide new explanation whereby the interactions between genetic elements and epigenetic modifications signed by environmental agents may be responsible for autoimmune disease initiation and perpetuation. It is aimed through this article to review recent progress attempting to reveal how epigenetics associates with the pathogenesis of autoimmune diseases.

  13. Window to 'Clovis's' Altered Past

    Science.gov (United States)

    2004-01-01

    This image taken by the Mars Exploration Rover Spirit shows a rock outcrop dubbed 'Clovis.' The rock was discovered to be softer than other rocks studied so far at Gusev Crater after the rover easily ground a hole (center) into it with its rock abrasion tool. An analysis of the interior of the hole with the rover's alpha particle X-ray spectrometer found higher concentrations of sulfur, bromine and chlorine compared to basaltic, or volcanic, rocks at Gusev. This might indicate that Clovis was chemically altered, and that fluids once flowed through the rock depositing these elements. Spirit's solar panels can be seen in the foreground. This image was taken by the rover's navigation camera on sol 205 (July 31, 2004).

  14. Self-alteration in HRI

    DEFF Research Database (Denmark)

    Yamazaki, Ryuji; Nørskov, Marco

    Humanlike androids are being developed with the ambition to be immersed into our daily life and meet us on an equal level in social interaction. The possibilities and limitations of these types of robots can potentially change societies and Human-Robot Interaction might affect the very way in which...... and Denmark, we examine how Telenoid, a new type of teleoperated android robot designed as a minimalistic human, affect people in the real world. We introduce Telenoid to real-world as the fields of elderly care and child education by focusing on the social aspects of the android robot that might facilitate...... the ways in which our subjectivity can be innerly transformed, decentred, in other words, self-altered. In our trials so far, we have been investigating the potential of teleoperated androids, which are embodied telecommunication media with humanlike appearances. By conducting pilot studies in Japan...

  15. Monetary benefits of preventing childhood lead poisoning with lead-safe window replacement.

    Science.gov (United States)

    Nevin, Rick; Jacobs, David E; Berg, Michael; Cohen, Jonathan

    2008-03-01

    Previous estimates of childhood lead poisoning prevention benefits have quantified the present value of some health benefits, but not the costs of lead paint hazard control or the benefits associated with housing and energy markets. Because older housing with lead paint constitutes the main exposure source today in the US, we quantify health benefits, costs, market value benefits, energy savings, and net economic benefits of lead-safe window replacement (which includes paint stabilization and other measures). The benefit per resident child from improved lifetime earnings alone is $21,195 in pre-1940 housing and $8685 in 1940-59 housing (in 2005 dollars). Annual energy savings are $130-486 per housing unit, with or without young resident children, with an associated increase in housing market value of $5900-14,300 per housing unit, depending on home size and number of windows replaced. Net benefits are $4490-5,629 for each housing unit built before 1940, and $491-1629 for each unit built from 1940-1959, depending on home size and number of windows replaced. Lead-safe window replacement in all pre-1960 US housing would yield net benefits of at least $67 billion, which does not include many other benefits. These other benefits, which are shown in this paper, include avoided Attention Deficit Hyperactivity Disorder, other medical costs of childhood lead exposure, avoided special education, and reduced crime and juvenile delinquency in later life. In addition, such a window replacement effort would reduce peak demand for electricity, carbon emissions from power plants, and associated long-term costs of climate change.

  16. Paternal Age Alters Social Development in Offspring.

    Science.gov (United States)

    Janecka, Magdalena; Haworth, Claire M A; Ronald, Angelica; Krapohl, Eva; Happé, Francesca; Mill, Jonathan; Schalkwyk, Leonard C; Fernandes, Cathy; Reichenberg, Abraham; Rijsdijk, Frühling

    2017-05-01

    Advanced paternal age (APA) at conception has been linked with autism and schizophrenia in offspring, neurodevelopmental disorders that affect social functioning. The current study explored the effects of paternal age on social development in the general population. We used multilevel growth modeling to investigate APA effects on socioemotional development from early childhood until adolescence, as measured by the Strengths and Difficulties Questionnaire (SDQ) in the Twins Early Development Study (TEDS) sample. We also investigated genetic and environmental underpinnings of the paternal age effects on development, using the Additive genetics, Common environment, unique Environment (ACE) and gene-environment (GxE) models. In the general population, both very young and advanced paternal ages were associated with altered trajectory of social development (intercept: p = .01; slope: p = .03). No other behavioral domain was affected by either young or advanced age at fatherhood, suggesting specificity of paternal age effects. Increased importance of genetic factors in social development was recorded in the offspring of older but not very young fathers, suggesting distinct underpinnings of the paternal age effects at these two extremes. Our findings highlight that the APA-related deficits that lead to autism and schizophrenia are likely continuously distributed in the population. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  17. Blood lead levels and risk factors for lead poisoning among children in Jakarta, Indonesia

    Energy Technology Data Exchange (ETDEWEB)

    Albalak, Rachel; Noonan, Gary; Buchanan, Sharunda; Flanders, W. Dana; Gotway-Crawford, Carol; Blumenthal, Wendy; Curtis, Gerald; McGeehin, Michael A. [Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention, 1600 Clifton Rd. Mailstop E-19, Atlanta, GA 30333 (United States); Kim, Dennis; Tan, Regina [Epidemic Intelligence Service, Epidemiology Program Office, Centers for Disease Control and Prevention, 1600 Clifton Rd. Mailstop D-18, Atlanta, GA 30333 (United States); Jones, Robert L. [Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, 1600 Clifton Rd. Mailstop F-18, Atlanta, GA 30333 (United States); Sulaiman, Rini [Swisscontact, Jl. Wijaya XII No. 44, Jakarta (Indonesia) 12160

    2003-01-01

    The phase-out of leaded gasoline began in Jakarta, Indonesia on July 1, 2001. We evaluated mean blood lead levels (BLLs) and the prevalence of elevated BLLs of Jakarta school children and assessed risk factors for lead exposure in these children before the beginning of the phase-out activities. The study involved a population-based, cross-sectional blood lead survey that included capillary blood lead sampling and a brief questionnaire on risk factors for lead poisoning. A cluster survey design was used. Forty clusters, defined as primary schools in Jakarta, and 15 2nd- and 3rd-grade children in each cluster were randomly selected for participation in the study. The average age of children in this study was 8.6 years (range 6-12) and the geometric mean BLL of the children was 8.6 {mu}g/dl (median: 8.6 {mu}g/dl; range: 2.6-24.1 {mu}g/dl) (n=397). Thirty-five percent of children had BLLs {>=}10 {mu}g/dl and 2.4% had BLLs {>=}20 {mu}g/dl. Approximately one-fourth of children had BLLs 10-14.9 {mu}g/dl. In multivariate models, level of education of the child's primary caregiver, water collection method, home varnishing and occupational recycling of metals, other than lead, by a family member were predictors of log BLLs after adjustment for age and sex. BLLs of children who lived near a highway or major intersection were significantly higher than those of children who lived near a street with little or no traffic when level of education was not included in the model. Water collection method was a significant predictor of BLLs {>=}10 {mu}g/dl after adjustment for age and sex. BLLs in children in this study were moderately high and consistent with BLLs of children in other countries where leaded gasoline is used. With the phase-out of leaded gasoline, BLLs of children in Jakarta are expected to rapidly decline as they have in other countries that have phased lead out of gasoline.

  18. The surgery of peripheral nerves (including tumors)

    DEFF Research Database (Denmark)

    Fugleholm, Kåre

    2013-01-01

    Surgical pathology of the peripheral nervous system includes traumatic injury, entrapment syndromes, and tumors. The recent significant advances in the understanding of the pathophysiology and cellular biology of peripheral nerve degeneration and regeneration has yet to be translated into improved...

  19. Including Indigenous Minorities in Decision-Making

    DEFF Research Database (Denmark)

    Pristed Nielsen, Helene

    Based on theories of public sphere participation and deliberative democracy, this book presents empirical results from a study of experiences with including Aboriginal and Maori groups in political decision-making in respectively Western Australia and New Zealand...

  20. Lung Disease Including Asthma and Adult Vaccination

    Science.gov (United States)

    ... Diseases Resources Lung Disease including Asthma and Adult Vaccination Language: English (US) Español (Spanish) Recommend on Facebook ... more about health insurance options. Learn about adult vaccination and other health conditions Asplenia Diabetes Heart Disease, ...

  1. Births and deaths including fetal deaths

    Data.gov (United States)

    U.S. Department of Health & Human Services — Access to a variety of United States birth and death files including fetal deaths: Birth Files, 1968-2009; 1995-2005; Fetal death file, 1982-2005; Mortality files,...

  2. Correlations in particle production in proton-lead and lead-lead collisions at the LHC

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00361447

    In high-energy heavy-ion collisions at the Large Hadron Collider (LHC), a hot and dense state of matter called the Quark-Gluon Plasma (QGP) is formed. The initial collision geometry and the subsequent expansion during the QGP stage result in the correlations of produced particles, through which the properties of the QGP can be investigated. Two analyses based on the geometrical correlations of produced particles, one in proton-lead (p–Pb) collisions and the other in lead-lead (Pb–Pb) collisions, are presented in this thesis. The data analyzed in this thesis were collected with the ALICE detector at the LHC in p– Pb collisions at a nucleon–nucleon center-of-mass energy of 5.02 TeV, and Pb–Pb collisions at a nucleon–nucleon center-of-mass energy of 2.76 TeV. In the forward-central two-particle correlation analysis in p–Pb collisions, two-particle an- gular correlations between trigger particles in the forward pseudorapidity range (2.5 < |η| < 4.0) and associated particles in the central ran...

  3. Lead reactor strategy economical analysis

    International Nuclear Information System (INIS)

    Ciotti, Marco

    2013-01-01

    Conclusions: • A first attempt to evaluate LFR power plant electricity production cost has been performed; • Electricity price is similar to Gen III + plants; • The estimation accuracy is probably low; • Possible costs reduction could arise from coolant characteristics that may improve safety and simplicity by design; • Accident perception, not acceptable by public opinion, may be changed with low potential energy system (non exploding coolant); • Sustainability improvement could open to a better Public acceptance, depending on us. • Problems may arise in coupling a high capital cost low fuel cost plant in a grid with large amount of intermittent sources with priority dispatch. • Lead fast reactors can compete

  4. The Self-Leading Customer

    DEFF Research Database (Denmark)

    Sørensen, Kirsten Bonde

    2012-01-01

    This paper refers to a Ph.D. design research, conducted in a medium sized Danish bank. The research demonstrates a human-centred perspective and resulted in a radical new type of banking service represented in the MoneyWorkshop. The MoneyWorkshop helps customers uncover their dominant values...... and emotions and makes them increasingly aware of their preferred personal values related to money. Participation in this workshop made customers increasingly empowered and ‘self-leading’. People even changed their ‘money behaviour’ – now in accordance with their values. The paper explains the Money......-Leading Customer...

  5. The art of leading meetings.

    Science.gov (United States)

    English, C B

    1987-05-01

    The ability to skillfully lead meetings can contribute to a manager's effectiveness. There are four types of meetings, each serving different needs and requiring different leadership. A manager must know when to hold meetings, what leadership style is appropriate, how and when to use participative management, and how to facilitate a consensus. Considerable planning must be done before a meeting is held. Various leadership and communication skills are required to effectively open, conduct, and close a meeting. Finally, the leader needs to know how to deal with participants who become problems.

  6. Lead-nickel electrochemical batteries

    CERN Document Server

    Glaize, Christian

    2012-01-01

    The lead-acid accumulator was introduced in the middle of the 19th Century, the diverse variants of nickel accumulators between the beginning and the end of the 20th Century. Although old, these technologies are always very present on numerous markets. Unfortunately they are still not used in optimal conditions, often because of the misunderstanding of the internal electrochemical phenomena.This book will show that batteries are complex systems, made commercially available thanks to considerable amounts of scientific research, empiricism and practical knowledge. However, the design of

  7. Soft mode of lead zirconate

    International Nuclear Information System (INIS)

    Pan'ko, G.F.; Prisedskij, V.V.; Klimov, V.V.

    1983-01-01

    Anisotropic diffusional scattering of electrons on PbZrO 3 crystal in the temperature range of phase transition has been recorded. As a result of its analysis it has been established that in lead zirconate the rotational vibrational mode G 25 plays the role of soft mode. The experiment is carried out using PbZrO 3 monocrystals in translucent electron microscope EhM-200, operating in the regime of microdiffraction at accelerating voltage of 150 kV and beam current 50 μA; sample preparation is realized using the method of shearing and fragmentation

  8. KARYOTYPE ALTERATIONS AFTER HYBRIDIZATION BETWEEN Pennisetum purpureum AND Pennisetum glaucum

    Directory of Open Access Journals (Sweden)

    Gabriela Barreto dos Reis

    2015-10-01

    Full Text Available ABSTRACTNapier grass and pearl millet are tropical forages from the genus Pennisetum. The variability in those species is explored in breeding programs of forages, as well as in the production of interspecific hybrids. Hybridization is a phenomenon that leads to intergenomic conflicts following the elimination of genomic sequences. In this sense, the present work aimed to study the genomic alterations occurring after interspecific hybridization of pearl millet and Napier grass with the use of cytogenetics and flow cytometry tools. These methods allowed the evaluation of chromosome morphometry, DNA content and genomic ratio in pearl millet, Napier grass and hybrids. It was observed that pearl millet and Napier grass have chromosomes with superposed size. The hybrid presents chromosomes that are smaller than expected, leading to karyotype alterations. Additionally, comparing the DNA content of parents and hybrids, loss of DNA content was demonstrated. Further, changes in the pearl millet and Napier grass genome ratio were also verified in the hybrid nucleus. Moreover, genomic rearrangements were shown to occur through karyotype alterations in the hybrid.

  9. Alterations In Lipid Profile Of Patients With Advanced Cervical Cancer

    African Journals Online (AJOL)

    Background The changes in lipid profile have long been associated with cancer because lipids play key role in maintenance of cell integrity. Aims. The study evaluated alterations in plasma lipid profile in patients with advanced squamous cervical cancer. Materials And Method This hospital-based study included 30 cervical ...

  10. The landscape of genomic alterations across childhood cancers

    NARCIS (Netherlands)

    Gröbner, Susanne N.; Worst, Barbara C.; Weischenfeldt, Joachim; Buchhalter, Ivo; Kleinheinz, Kortine; Rudneva, Vasilisa A.; Johann, Pascal D.; Balasubramanian, Gnana Prakash; Segura-Wang, Maia; Brabetz, Sebastian; Bender, Sebastian; Hutter, Barbara; Sturm, Dominik; Pfaff, Elke; Hübschmann, Daniel; Zipprich, Gideon; Heinold, Michael; Eils, Jürgen; Lawerenz, Christian; Erkek, Serap; Lambo, Sander; Waszak, Sebastian; Blattmann, Claudia; Borkhardt, Arndt; Kuhlen, Michaela; Eggert, Angelika; Fulda, Simone; Gessler, Manfred; Wegert, Jenny; Kappler, Roland; Baumhoer, Daniel; Burdach, Stefan; Kirschner-Schwabe, Renate; Kontny, Udo; Kulozik, Andreas E.; Lohmann, Dietmar; Hettmer, Simone; Eckert, Cornelia; Bielack, Stefan; Nathrath, Michaela; Niemeyer, Charlotte; Richter, Günther H.; Schulte, Johannes; Siebert, Reiner; Westermann, Frank; Molenaar, Jan J.; Vassal, Gilles; Witt, Hendrik; Burkhardt, Birgit; Kratz, Christian P.; Witt, Olaf; van Tilburg, Cornelis M.; Kramm, Christof M.; Fleischhack, Gudrun; Dirksen, Uta; Rutkowski, Stefan; Frühwald, Michael; von Hoff, Katja; Wolf, Stephan; Klingebiel, Thomas; Koscielniak, Ewa; Landgraf, Pablo; Koster, Jan; Resnick, Adam C.; Zhang, Jinghui; Liu, Yanling; Zhou, Xin; Waanders, Angela J.; Zwijnenburg, Danny A.; Raman, Pichai; Brors, Benedikt; Weber, Ursula D.; Northcott, Paul A.; Pajtler, Kristian W.; Kool, Marcel; Piro, Rosario M.; Korbel, Jan O.; Schlesner, Matthias; Eils, Roland; Jones, David T. W.; Lichter, Peter; Chavez, Lukas; Zapatka, Marc; Pfister, Stefan M.; Weber, Ursula; Korshunov, Andrey; Pfister, Stefan; Reifenberger, Guido; Felsberg, Jörg; von Kalle, Christof; Schmidt, Manfred; Bartholomä, Cynthia; Taylor, Michael; Jones, David; Jäger, Natalie; Korbel, Jan; Stütz, Adrian; Rausch, Tobias; Radlwimmer, Bernhard; Yaspo, Marie-Laure; Lehrach, Hans; Warnatz, Hans-Jörg; Wagner, Susanne; Haake, Andrea; Richter, Julia; Richter, Gesine; Lawerenz, Chris; Kerssemakers, Jules; Jaeger-Schmidt, Christina; Scholz, Ingrid; Bergmann, Anke K.; Borst, Christoph; Claviez, Alexander; Dreyling, Martin; Eberth, Sonja; Einsele, Hermann; Frickhofen, Norbert; Haas, Siegfried; Hansmann, Martin-Leo; Karsch, Dennis; Kneba, Michael; Lisfeld, Jasmin; Mantovani-Löffler, Luisa; Rohde, Marius; Ott, German; Stadler, Christina; Staib, Peter; Stilgenbauer, Stephan; Trümper, Lorenz; Zenz, Thorsten; Kube, Dieter; Küppers, Ralf; Weniger, Marc; Hummel, Michael; Klapper, Wolfram; Kostezka, Ulrike; Lenze, Dido; Möller, Peter; Rosenwald, Andreas; Szczepanowski, Monika; Ammerpohl, Ole; Aukema, Sietse M.; Binder, Vera; Hoell, Jessica I.; Leich, Ellen; López, Cristina; Nagel, Inga; Pischimariov, Jordan; Rosenstiel, Philip; Schilhabel, Markus; Schreiber, Stefan; Vater, Inga; Wagener, Rabea; Bernhart, Stephan H.; Binder, Hans; Doose, Gero; Hoffmann, Steve; Hopp, Lydia; Kretzmer, Helene; Kreuz, Markus; Langenberger, David; Loeffler, Markus; Rosolowski, Maciej; Stadler, Peter F.; Sungalee, Stephanie

    2018-01-01

    Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children,

  11. Altered mitochondrial regulation in quadriceps muscles of patients with COPD

    DEFF Research Database (Denmark)

    Naimi, Ashley I; Bourbeau, Jean; Perrault, Helene

    2011-01-01

    Evidence exists for locomotor muscle impairment in patients with chronic obstructive pulmonary disease (COPD), including fiber type alterations and reduced mitochondrial oxidative capacity. In this study high-resolution respirometry was used to quantify oxygen flux in permeabilized fibres from bi...

  12. Alterations in reducing sugar in Triticum aestivum under irrigated ...

    African Journals Online (AJOL)

    This research was conducted with the objective of observing alterations in reducing sugars, which may play a part in distinguishing tolerant and susceptible genotypes. The experimental material consisted of thirteen wheat genotypes including eleven bread wheat advanced lines, one synthetic hexaploid and its durum ...

  13. Alterations in reducing sugar in Triticum aestivum under irrigated ...

    African Journals Online (AJOL)

    DELL

    2012-03-13

    Mar 13, 2012 ... This research was conducted with the objective of observing alterations in reducing sugars, which may play a part in distinguishing tolerant and susceptible genotypes. The experimental material consisted of thirteen wheat genotypes including eleven bread wheat advanced lines, one synthetic hexaploid ...

  14. Circadian Disruption Leads to Loss of Homeostasis and Disease

    Directory of Open Access Journals (Sweden)

    Carolina Escobar

    2011-01-01

    Full Text Available The relevance of a synchronized temporal order for adaptation and homeostasis is discussed in this review. We present evidence suggesting that an altered temporal order between the biological clock and external temporal signals leads to disease. Evidence mainly based on a rodent model of “night work” using forced activity during the sleep phase suggests that altered activity and feeding schedules, out of phase from the light/dark cycle, may be the main cause for the loss of circadian synchrony and disease. It is proposed that by avoiding food intake during sleep hours the circadian misalignment and adverse consequences can be prevented. This review does not attempt to present a thorough revision of the literature, but instead it aims to highlight the association between circadian disruption and disease with special emphasis on the contribution of feeding schedules in circadian synchrony.

  15. Ingestion of lead from ammunition and lead concentrations in white-tailed sea eagles (Haliaeetus albicilla) in Sweden

    International Nuclear Information System (INIS)

    Helander, B.; Axelsson, J.; Borg, H.; Holm, K.; Bignert, A.

    2009-01-01

    In this study we show for the first time that lead poisoning from ammunition is a significant mortality factor for white-tailed sea eagle (WSE) (Haliaeetus albicilla) in Sweden. We analyzed 118 WSEs collected between 1981 and 2004 from which both liver and kidney samples could be taken. A total of 22% of all eagles examined had elevated (> 6 μg/g d.w.) lead concentrations, indicating exposure to leaded ammunition, and 14% of the individuals had either liver or kidney lead concentrations diagnostic of lethal lead poisoning (> 20 μg/g d.w.). Lead concentrations in liver and kidney were significantly correlated. In individuals with lead levels 20 μg/g, concentrations were significantly higher in liver. The lead isotope ratios indicate that the source of lead in individuals with lethal concentrations is different from that of individuals exhibiting background concentrations of lead ( 10 times higher than concentrations reported for Baltic fish from the same time period. In contrast to other biota there was no decrease in lead concentrations in WSE over the study period. The proportion of lead poisoned WSE remained unchanged over the study period, including two years after a partial ban of lead shot was enforced in 2002 for shallow wetlands. The use of lead in ammunition poses a threat to all raptors potentially feeding on shot game or offal. The removal of offal from shot game and alternatives to leaded ammunition needs to be implemented in order to prevent mortality from lead in raptors and scavengers.

  16. String formation beyond leading colour

    Energy Technology Data Exchange (ETDEWEB)

    Christiansen, Jesper R. [Department of Astronomy and Theoretical Physics, Lund University,Sölvegatan 14, Lund (Sweden); Theoretical Physics, CERN,CH-1211, Geneva 23 (Switzerland); Skands, Peter Z. [Theoretical Physics, CERN,CH-1211, Geneva 23 (Switzerland); School of Physics and Astronomy, Monash University,VIC-3800 (Australia)

    2015-08-03

    We present a new model for the hadronisation of multi-parton systems, in which colour correlations beyond leading N{sub C} are allowed to influence the formation of confining potentials (strings). The multiplet structure of SU(3) is combined with a minimisation of the string potential energy, to decide between which partons strings should form, allowing also for “baryonic” configurations (e.g., two colours can combine coherently to form an anticolour). In e{sup +}e{sup −}collisions, modifications to the leading-colour picture are small, suppressed by both colour and kinematics factors. But in pp collisions, multi-parton interactions increase the number of possible subleading connections, counteracting their naive 1/N{sub C}{sup 2} suppression. Moreover, those that reduce the overall string lengths are kinematically favoured. The model, which we have implemented in the PYTHIA 8 generator, is capable of reaching agreement not only with the important 〈p{sub ⊥}〉(n{sub charged}) distribution but also with measured rates (and ratios) of kaons and hyperons, in both ee and pp collisions. Nonetheless, the shape of their p{sub ⊥} spectra remains challenging to explain.

  17. Finland's leading natural gas company

    International Nuclear Information System (INIS)

    Anon.

    2000-01-01

    The ownership structure of Finland's leading natural gas company, Gasum, changed fundamentally in 1999, and the company is now no longer a subsidiary of Fortum Corporation. 'Our new strong and broad ownership base will enable us to develop the natural gas business and pipeline network in Finland in response to the requirements of our Finnish customers', says Antero Jaennes, Gasum's Chairman and CEO, who stresses that Gasum is committed to remaining the leading developer of the Finnish natural gas market and the number-one gas supplier. Natural gas usage in Finland in 1999 totalled 3.9 billion m 3 (38.7 TWh), unchanged from 1998. Natural gas accounted for 11% of Finland's total primary energy need, as it did in 1998. The proportion of natural gas used in district heating rose by 2% to 36%, and moved down 2% in power generation to 10%. Industry's use of natural gas fell 1% to 17%. 75% of natural gas was used in combined heat and power (CHP) generation in industry and district heating. In 2000, Gasum expects to sell 4 billion m 3 of natural gas (40 TWh)

  18. Influence of experimental distemper infection on the distribution of lead in dogs previously subacutely intoxicated with lead carbonate

    Energy Technology Data Exchange (ETDEWEB)

    White, D.J.; Marshall, A.J.; McLeod, S.

    1975-01-01

    The ability of experimental canine distemper infection to mobilize body lead deposits has been studied in Beagle dogs previously subacutely intoxicated with lead carbonate. For comparative purposes dogs were included which had either received lead only or distemper only or remained undosed. It was found that in dogs predosed with lead, distemper infection resulted in a significant increase in lead levels in blood and urine; this coincided with the peak body temperatures reached on the third day post infection. It was also found that the lead content of the liver and bone of these dogs was considerably higher than that of dogs receiving lead alone; at the same time bone phosphorus showed a marked decrease while bone calcium values remained similar to undosed controls.

  19. Lead exposure in US worksites: A literature review and development of an occupational lead exposure database from the published literature

    Science.gov (United States)

    Koh, Dong-Hee; Locke, Sarah J.; Chen, Yu-Cheng; Purdue, Mark P.; Friesen, Melissa C.

    2016-01-01

    Background Retrospective exposure assessment of occupational lead exposure in population-based studies requires historical exposure information from many occupations and industries. Methods We reviewed published US exposure monitoring studies to identify lead exposure measurement data. We developed an occupational lead exposure database from the 175 identified papers containing 1,111 sets of lead concentration summary statistics (21% area air, 47% personal air, 32% blood). We also extracted ancillary exposure-related information, including job, industry, task/location, year collected, sampling strategy, control measures in place, and sampling and analytical methods. Results Measurements were published between 1940 and 2010 and represented 27 2-digit standardized industry classification codes. The majority of the measurements were related to lead-based paint work, joining or cutting metal using heat, primary and secondary metal manufacturing, and lead acid battery manufacturing. Conclusions This database can be used in future statistical analyses to characterize differences in lead exposure across time, jobs, and industries. PMID:25968240

  20. Upper abdominal malignancies (not including esophagus)

    International Nuclear Information System (INIS)

    Rich, Tyvin A.

    1996-01-01

    combined with chemotherapy in patients with unresectable disease, and that radiation therapy and chemotherapy is of value as an adjuvant therapy in patients who have had a potentially curative surgical resection. There is relatively little information on the treatment of cancers of the biliary tract with radiation therapy. However, the existing data on recurrence patterns and therapy will be reviewed. The use of brachytherapy for patients with biliary obstruction will be discussed. In most tumors of the GI tract, the combination of radiation therapy with 5-FU chemotherapy seems to be more effective than radiation therapy alone. Newer information suggests that modulators of 5-FU effect such as leucovorin, or altered modes of administration such as continuous infusion, may be beneficial. These issues will be discussed as they relate to the upper abdominal malignancies

  1. Upper abdominal malignancies (not including esophagus)

    International Nuclear Information System (INIS)

    Tepper, Joel E.

    1995-01-01

    combined with chemotherapy in patients with unresectable disease, and that radiation therapy and chemotherapy is of value as an adjuvant therapy in patients who have had a potentially curative surgical resection. There is relatively little information on the treatment of cancers of the biliary tract with radiation therapy. However, the existing data on recurrence patterns and therapy will be reviewed. The use of brachytherapy for patients with biliary obstruction will be discussed. In most tumors of the GI tract, the combination of radiation therapy with 5-FU chemotherapy seems to be more effective than radiation therapy alone. Newer information suggests that modulators of 5-FU effect such as leucovorin, or altered modes of administration such as continuous infusion, may be beneficial. These issues will be discussed as they relate to the upper abdominal malignancies

  2. Anatomy of lead poisoning | Duru | Research Journal of Health ...

    African Journals Online (AJOL)

    Advances in molecular biology have however tremendously helped in unravelling more mechanisms of lead toxicity. In this review it is ... Results: The primary form of lead toxicity is by oxidative stress mechanisms, apoptosis and necrosis involving cellular pathways including both mitochondria and cytoplasmic pathways.

  3. Lead and Conduct Problems: A Meta-Analysis

    Science.gov (United States)

    Marcus, David K.; Fulton, Jessica J.; Clarke, Erin J.

    2010-01-01

    This meta-analysis examined the association between conduct problems and lead exposure. Nineteen studies on 8,561 children and adolescents were included. The average "r" across all 19 studies was 0.19 (p less than 0.001), which is considered a medium effect size. Studies that assessed lead exposure using hair element analysis yielded…

  4. Lead poisoning in shooting-range workers in Gauteng Province ...

    African Journals Online (AJOL)

    Its many useful properties have resulted in lead being widely used in modern life. However, research has revealed lead to be highly toxic and associated with a wide range of detrimental health effects, including impaired cognitive function,[1] hearing deficits, behavioural abnormalities, aggressive behaviour,[2] anaemia and ...

  5. Available: lead plate from COMPASS experiment

    CERN Multimedia

    The COMPASS collaboration

    2014-01-01

    The COMPASS collaboration would like to offer the possibility to take over a large and thick lead plate, since it is not required anymore in the spectrometer.   It has the following dimensions: thickness 100 mm, width 4.4 m and height 2.0 m, with a square hole in the middle with dimensions of 40 cm x 40 cm. The measured weight including the metal frame it is housed in is 10,180 kg. The CERN stores reference is 44.13.30.100.9. Please contact Erwin Bielert (erwin.bielert@cern.ch or 160539) for further information and details.

  6. Leading a Recovery-oriented Social Enterprise.

    Science.gov (United States)

    Raeburn, Toby; Hungerford, Catherine; Sayers, Jan; Escott, Phil; Lopez, Violeta; Cleary, Michelle

    2015-05-01

    Recovery-oriented mental health services promote the principles of recovery, such as hope and optimism, and are characterized by a personalized approach to developing consumer self-determination. Nurse leaders are increasingly developing such services as social enterprises, but there is limited research on the leadership of these programs. Leading a recovery-oriented mental health nurse social enterprise requires visionary leadership, collaboration with consumers and local health providers, financial viability, and commitment to recovery-focused practice. This article describes the framework of an Australian mental health nursing social enterprise, including the service attributes and leadership lessons that have been learned from developing program sustainability.

  7. Lead Slowing Down Spectrometer Status Report

    International Nuclear Information System (INIS)

    Warren, Glen A.; Anderson, Kevin K.; Bonebrake, Eric; Casella, Andrew M.; Danon, Yaron; Devlin, M.; Gavron, Victor A.; Haight, R.C.; Imel, G.R.; Kulisek, Jonathan A.; O'Donnell, J.M.; Weltz, Adam

    2012-01-01

    This report documents the progress that has been completed in the first half of FY2012 in the MPACT-funded Lead Slowing Down Spectrometer project. Significant progress has been made on the algorithm development. We have an improve understanding of the experimental responses in LSDS for fuel-related material. The calibration of the ultra-depleted uranium foils was completed, but the results are inconsistent from measurement to measurement. Future work includes developing a conceptual model of an LSDS system to assay plutonium in used fuel, improving agreement between simulations and measurement, design of a thorium fission chamber, and evaluation of additional detector techniques.

  8. Isolators Including Main Spring Linear Guide Systems

    Science.gov (United States)

    Goold, Ryan (Inventor); Buchele, Paul (Inventor); Hindle, Timothy (Inventor); Ruebsamen, Dale Thomas (Inventor)

    2017-01-01

    Embodiments of isolators, such as three parameter isolators, including a main spring linear guide system are provided. In one embodiment, the isolator includes first and second opposing end portions, a main spring mechanically coupled between the first and second end portions, and a linear guide system extending from the first end portion, across the main spring, and toward the second end portion. The linear guide system expands and contracts in conjunction with deflection of the main spring along the working axis, while restricting displacement and rotation of the main spring along first and second axes orthogonal to the working axis.

  9. Electrochemical cell structure including an ionomeric barrier

    Science.gov (United States)

    Lambert, Timothy N.; Hibbs, Michael

    2017-06-20

    An apparatus includes an electrochemical half-cell comprising: an electrolyte, an anode; and an ionomeric barrier positioned between the electrolyte and the anode. The anode may comprise a multi-electron vanadium phosphorous alloy, such as VP.sub.x, wherein x is 1-5. The electrochemical half-cell is configured to oxidize the vanadium and phosphorous alloy to release electrons. A method of mitigating corrosion in an electrochemical cell includes disposing an ionomeric barrier in a path of electrolyte or ion flow to an anode and mitigating anion accumulation on the surface of the anode.

  10. Electric Power Monthly, August 1990. [Glossary included

    Energy Technology Data Exchange (ETDEWEB)

    1990-11-29

    The Electric Power Monthly (EPM) presents monthly summaries of electric utility statistics at the national, Census division, and State level. The purpose of this publication is to provide energy decisionmakers with accurate and timely information that may be used in forming various perspectives on electric issues that lie ahead. Data includes generation by energy source (coal, oil, gas, hydroelectric, and nuclear); generation by region; consumption of fossil fuels for power generation; sales of electric power, cost data; and unusual occurrences. A glossary is included.

  11. Devices that Alter the Tip Vortex of a Rotor

    Science.gov (United States)

    McAlister, Kenneth W.; Tung, Chee; Heineck, James T.

    2001-01-01

    Small devices were attached near the tip of a hovering rotor blade 'in order to alter the structure and trajectory of the trailing vortex. Stereo particle image velocimetry (PIV) images were used to quantify the wake behind the rotor blade during the first revolution. A procedure for analyzing the 3D-velocity field is presented that includes a method for accounting for vortex wander. The results show that a vortex generator can alter the trajectory of the trailing vortex and that a major change in the size and intensity of the trailing vortex can be achieved by introducing a high level of turbulence into the core of the vortex.

  12. Diversification of Smallholder Tobacco Systems to include ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Tobacco is the mainstay of the economy of Malawi, accounting for over 70% of export earnings. Of the 100 000 members of the National Smallholder Farmers' Association of Malawi (NASFAM), 60% rely on tobacco for their sole source of income. Like their counterparts elsewhere, they face many difficulties, including: ...

  13. BIOLOGIC AND ECONOMIC EFFECTS OF INCLUDING DIFFERENT ...

    African Journals Online (AJOL)

    The biologic and economic effects of including three agro-industrial by-products as ingredients in turkey poult diets were investigated using 48 turkey poults in a completely randomised design experiment. Diets were formulated to contain the three by-products – wheat offal, rice husk and palm kernel meal, each at 20% level ...

  14. Extending flood damage assessment methodology to include ...

    African Journals Online (AJOL)

    Optimal and sustainable flood plain management, including flood control, can only be achieved when the impacts of flood control measures are considered for both the man-made and natural environments, and the sociological aspects are fully considered. Until now, methods/models developed to determine the influences ...

  15. Including Children Dependent on Ventilators in School.

    Science.gov (United States)

    Levine, Jack M.

    1996-01-01

    Guidelines for including ventilator-dependent children in school are offered, based on experience with six such students at a New York State school. Guidelines stress adherence to the medical management plan, the school-family partnership, roles of the social worker and psychologist, orientation, transportation, classroom issues, and steps toward…

  16. Musculoskeletal ultrasound including definitions for ultrasonographic pathology

    DEFF Research Database (Denmark)

    Wakefield, RJ; Balint, PV; Szkudlarek, Marcin

    2005-01-01

    Ultrasound (US) has great potential as an outcome in rheumatoid arthritis trials for detecting bone erosions, synovitis, tendon disease, and enthesopathy. It has a number of distinct advantages over magnetic resonance imaging, including good patient tolerability and ability to scan multiple joint...

  17. Modernizing Agrifood Markets : Including Small Producers in ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Against this baseline data, they will endeavor to identify success stories or examples of interventions that ensure small farmers' access to modernizing agrifood markets. The research will inform a set of policy recommendations to be promoted through policy platforms in a large number of developing countries, including but ...

  18. Including Students with Visual Impairments: Softball

    Science.gov (United States)

    Brian, Ali; Haegele, Justin A.

    2014-01-01

    Research has shown that while students with visual impairments are likely to be included in general physical education programs, they may not be as active as their typically developing peers. This article provides ideas for equipment modifications and game-like progressions for one popular physical education unit, softball. The purpose of these…

  19. Numerical simulation of spark ignition including ionization

    NARCIS (Netherlands)

    Thiele, M; Selle, S; Riedel, U; Warnatz, J; Maas, U

    2000-01-01

    A detailed understanding of the processes associated Midi spark ignition, as a first step during combustion, is of great importance fur clean operation of spark ignition engines. In the past 10 years. a growing concern for environmental protection, including low emission of pollutants, has increased

  20. Multi-lead heat sink

    Science.gov (United States)

    Roose, L.D.

    1982-08-25

    The disclosure relates to a heat sink used to protect integrated circuits from the heat resulting from soldering them to circuit boards. A tubular housing contains a slidable member which engages somewhat inwardly extending connecting rods, each of which is rotatably attached at one end to the bottom of the housing. The other end of each rod is fastened to an expandable coil spring loop. As the member is pushed downward in the housing, its bottom edge engages and forces outward the connecting rods, thereby expanding the spring so that it will fit over an integrated circuit. After the device is in place, the member is slid upward and the spring contracts about the leads of the integrated circuit. Soldering is now conducted and the spring absorbs excess heat therefrom to protect the integrated circuit. The placement steps are repeated in reverse order to remove the heat sink for use again.